Plant Protection Products Regulations, 2009

L.N. 358 of 2009

PESTICIDES CONTROL ACT

(CAP. 430)

Plant Protection Products Regulations, 2009

IN exercise of the powers conferred by articles 4 and 5 of

the Pesticides Control Act, the Minister for Resources and Rural

Affairs, in consultation with the Prime Minister and with the

Minister for Social Policy, has made the following regulations:-

(1) The title of these regulations is the Plant Protection

Products Regulations, 2009.

(2) The scope of these Regulations is to transpose

Commission Directive 1991/414/EC of 15 July 1991 concerning

the placing of plant protection products on the market as last

amended by Commission Directive 2009/82/EC of 13 July

2009 and Council Directive 79/117/EEC of 21 December 1978

prohibiting the placing on the market and use of plant protection

products containing certain active substances.

(3) These regulations concern the authorization,

placing on the market, use and control of plant protection products

in commercial form and the placing on the market and control of

active substances intended for a use specified in regulation 2 (1).

(4) These regulations shall apply without prejudice

to the Dangerous Substances and Preparations Regulations, 2007

(L.N. 10 of 2007), and, where active substances are concerned,

without prejudice to the provisions concerning classification,

packaging and labeling in terms of The Dangerous Substances

(Notification) Regulations, 2001 (L.N. 318 of 2001).

(5) These regulations apply to the authorization

to place on the market plant protection products containing or

composed of genetically modified organisms, provided that

authorization to release them into the environment has been granted

after the risk to the environment has been assessed in accordance

with the provisions of Deliberate Release into the Environment of

Genetically Modified Organisms Regulations, 2002 (L.N. 170 of

2002).

(6) These regulations shall apply without prejudice to

Council Regulation (EC) No 304/2003 of the European Parliament

and of the Coucil of 28 January 2003 concerning the export and

import of dangerous chemicals.

ACTIVE SUBSTANCES AUTHORISED FOR USE IN PLANT PROTECTION PRODUCTS

General provisions applying to all substances listed in this Schedule

For the implementation of the uniform principles of Schedule VI in relation to each substance, the conclusions of the review report on it, and in particular the Appendices I and II thereof, as finalised in the

Standing Committee on Plant Health on the date indicated under‘specific provisions’for that substance shall be taken into account.

The Director shall keep available all review reports (except for confidential information within the meaning of

regulation 14 of these regulations) for consultation by any interested parties or shall make it available to them on specific request.

Number

Expiration of

Common name, identification,

Entry into

IUPAC name

Purity

Specific provisions

numbers

force

inclusion

Only uses as fungicide may be authorized.

For the following uses the following particular conditions apply

—post-harvest fruit, vegetable and potato treatments may only be

authorised when an appropriate decontamination system is available or a

risk assessment has demonstrated to the authorizing Member State that

(+)-1-(ß-allyloxy-

the discharge of the treatment solution does not have an unacceptable

2,4-

Imazalil

risk to the environment and in particular to aquatic organisms,

dichlorophenylethy-

CAS No 73790-28-0,

31 December

—post-harvest treatment of potatoes may only be authorised when a risk

l)imidazole or (+)-

975 g/kg

1 January 1999

35554-44-0

assessment has demonstrated to the authorizing Member State that the

allyl 1-(2,4-dichloro-

discharge of the processing waste from treated potatoes does not have

CIPAC No 335

phenyl)-2-imidazol-

an unacceptable risk to aquatic organisms,

1-ylethyl ether

—outdoor foliar uses may only be authorised when a risk assessment

has demonstrated to the authorizing Member State that the use has no

unacceptable effects on human and animal health and the environment.

Date of Standing Committee on Plant Health at which the review report

was finalised: 11 July 1997.

Only uses as fungicide may be authorised.

Methyl (E)-2-{2[6-

930 g/kg

In the decision making according to the Uniform Principles particular

Azoxystrobin

(2-cyanophenoxy)-

31 December

attention should be given to the impact on aquatic organisms. Author

(Z isomer

CAS No 131860-33-8

pyrimidin-4-yloxy]

1 July 1998

isation conditions should include appropriate risk mitigation measures.

max.

CIPAC No 571

phenyl}-3-methoxya-

Date of Standing Committee on Plant Health at which the review report

25 g/kg)

crylate

was finalised: 22 April 1998.

Expiration of

Common

name,

Entry

into

Number

IUPAC name

Purity

Specific provisions

identification, numbers

force

inclusion

Only uses as fungicide may be authorised.

Methyl (E)-2-meth-

In their decision making according to the Uniform Principles

Kresoxim-Methyl

oxyimino-2-[2-(o-

1 February

31 December

Member States shall pay particular attention to the protection of

CAS No 143390-89-0

910 g/kg

groundwater under vulnerable conditions.

tolyloxymethyl)

CIPAC No 568

Date of Standing Committee on Plant Health at which the review

phenyl]acetate

report was finalised: 16 October 1998.

Only uses as a fungicide may be authorised.

In their decision making according to the Uniform Principles

Member States

g/kg

—must pay particular attention to operator safety and must ensure

(8-tert-Butyl-1,4-

Spiroxamine

(diaster-

that the conditions of authorisation include appropriate protective

dioxa-spiro [4.5]

1 September

31 December

CAS No 1181134-30-8

eomers A

measures, and,

decan-2-ylmethyl)-

and B

CIPAC No 572

—must pay particular attention to the impact on aquatic organisms

ethyl-propyl-amine

combined)

and must ensure that the conditions of authorisation include, where

appropriate, risk mitigation measures.

Date of Standing Committee on Plant Health at which the review

report was finalised: 12 May 1999.

Only uses as herbicide may be authorised.

Aerial applications may not be authorised.

1-(4,6-dimethoxypyr-

In their decision making according to the Uniform Principles

imidin-2-yl)-3-[1-

Member States must pay particular attention to the impact on aquatic

Azimsulfuron

methyl-4-(2-methyl-

1 October

31 December

organisms and terrestrial non-target plants and must ensure that the

CAS No 120162-55-2

980 g/kg

2H-tetrazol-5-yl)-

conditions of authorisation include, where appropriate, risk

CIPAC No 584

mitigation measures (e.g. in rice cultivation minimum holding

pyrazol-5-

periods for water prior to discharge).

ylsulfonyl]-urea

Date of Standing Committee on Plant Health at which the review

report was finalised: 2 July 1999.

Number

Common

name,

identification,

Expiration of

IUPAC name

Purity

Entry into force

Specific provisions

numbers

inclusion

Only uses as herbicide may be authorised.

In their decision making according to the Uniform Principles Member

States

—shall take into account the additional information requested in point

7 of the Review Report,

—must pay particular attention to the protection of groundwater,

Fluroxypyr

4-amino-3,5-

1 December

31 December

—must pay particular attention to the impact on aquatic organisms and

CAS No 69377-81-7

dichloro-6-fluoro-2-

950 g/kg

must ensure that the conditions of authorisation include, where

CIPAC No 431

pyridyloxyacetic acid

appropriate, risk mitigation measures.

Member States shall inform the Commission if the requested

additional trials and information as outlined in point 7 of the Review

Report were not submitted by 1 December 2000.

Date of Standing Committee on Plant Health at which the review

report was finalised: 30 November 1999.

Only uses as herbicide may be authorised

In their decision making according to the uniform principles, Member

Methyl-2-(4-

States

Metsulfuron-methyl

methoxy-6-methyl-

—must pay particular attention to the protection of groundwater,

960 g/kg

1.7.2001

For the purposes of these regulations the following

definitions shall apply

“active substances” means substances or micro-

organisms including viruses, having general or specific

action

(a) against harmful organisms; or

(b)

on plants, parts of plants or plant products;

“advertising” in relation to plant protection products

includes any form of door-to-door information, canvassing

activity or inducement designed to promote the supply, sale or

use of plant protection products and without prejudice to the

generality of the foregoing in particular includes

(a) the advertising of plant protection products to

the general public or to persons who may be expected to

use or supply these products,

(b) the provision of inducements to prescribe or

supply plant protection products, by way of a gift, offer

or promise of any benefit or bonus, whether in money

or in kind, except when the intrinsic value of such an

inducement is minimal, and

(c) sponsorship of any meeting attended by

persons authorised to deal or who generally use these

products, but shall exclude

(i) the labelling and the accompanying

package leaflets, which are subject to the provisions

of regulations 15 and 16,

(ii) correspondence, even if accompanied by

material of a non-promotional nature, which is in

reply to a specific question about a particular plant

protection product, and

(iii) factual, informative, announcement

or reference material relating to pack changes,

adverse-effect warnings as part of general

precautions, trade catalogues, price lists and other

material of a similar nature provided that such

material does not include any product claim;

“animals” means animals belonging to species normally

fed and kept or consumed by man;

“authorization of a plant protection product” means

administrative act by which the Director responsible for

pesticides within the Malta Standards Authority, hereinafter

referred to as the Directorate following an application

submitted by an applicant, for the placing on the market of a

plant protection product;

“authorized representative” means any person duly

authorized by the Director to act on his behalf for any of the

purposes referred to in these regulations;

“dealing” means any activity in the manufacture, import,

export, transport, storage, distribution, presenting for sale or

sale of any plant protection product;

“environment” means water, air, land, wild species of

fauna and flora, and any interrelationship between them, as

well as any relationship with living organisms;

“harmful organisms” means pests of plants or plant

products belonging to the animal or plant kingdom, and also

viruses, bacteria and mycoplasmas and other pathogens;

“high-risk plant protection product” means any plant

protection product classified as toxic or highly toxic product

in accordance with regulation 19 of these regulations;

“integrated control” means the rational application of

a combination of biological, biotechnological, chemical,

cultural or plant-breeding measures whereby the use of

chemical plant protection products is limited to the strict

minimum necessary to maintain the pest population at levels

below those causing economically unacceptable damage or

loss;

“manufacturer” means the holder of a manufacturing

process for the manufacturing of a plant protection product;

“manufacturing” shall have the same meaning as is

assigned to it in the Act;

“minor crop” means any crop that is cultivated in Malta

except tomatoes, potatoes or grapes;

“placing on the market” means any supply, whether in

return for payment or free of charge, other than for storage

followed by consignment from the territory of the Community

or disposal. Importation of a plant protection product shall be

deemed to constitute placing on the market for the purposes

of these regulations;

“plant products” means products in the unprocessed state

or having undergone only simple preparation such as milling,

drying or pressing, derived from plants, but excluding plants

themselves as defined in point 6;

“plant protection products” means active substances and

preparations containing one or more active substances, put up

in the form in which they are supplied to the user, intended to

(a) protect plants or plant products against

all harmful organisms or prevent the action of such

organisms, in so far as such substances or preparations

are not otherwise defined below;

(b) influence the life processes of plants, other

than as a nutrient, such as growth regulators;

(c) preserve plant products, in so far as such

substances or products are not subject to special Council

or Commission provisions on preservatives;

(d) destroy undesired plants; or

(e) destroy parts of plants, check or prevent

undesired growth of plants;

“plants” means live plants and live parts of plants,

including fresh fruit and seeds;

“preparations” means mixtures or solutions composed

of two or more substances of which at least one is an active

substance, intended for use as plant protection products;

“professional user” means any person who acts as a

farmer or gardener and is authorized to purchase, transport,

store and use plant protection products in accordance with

these regulations. This does not apply for domestic use;

“professional users of high risk plant protection

products” means any person who is authorized to purchase,

transport, store and use high risk plant protection product;

“recognised country” means any member state of the

European Community;

“residues of plant protection products” means one

or more substances present in or on plants or products of

plant origin, edible animal products or elsewhere in the

environment and resulting from the use of a plant protection

product, including their metabolites and products resulting

from their degradation or reaction;

“substances” means chemical elements and their

compounds, as they occur naturally or by manufacture,

including any impurity inevitable resulting from the

manufacturing process;

“the Act” means the Pesticides Control Act;

REQUIREMENTS FOR THE DOSSIER TO BE SUBMITTED FOR THE

INCLUSION OF AN ACTIVE SUBSTANCE IN SCHEDULE I

INTRODUCTION

The information required shall

1.1. include a technical dossier supplying the information necessary for eval-

uating the foreseeable risks, whether immediate or delayed, which the

substance may entail for humans, animals and the environment and

containing at least the information and results of the studies referred to

below;

1.2. where relevant, be generated using test guidelines, according to the latest

adopted version, referred to or described in this Schedule; in the case of

studies initiated before the entry into force of the modification of this

Schedule, the information shall be generated using suitable internationally

or nationally validated test guidelines or, in the absence thereof, test

guidelines accepted by the director;

1.3. in the event of a test guideline being inappropriate or not described, or

where another one than those referred to in Annex II of Directive 414/1991

has been used, include a justification, which is acceptable to the director for

the guidelines used. In particular, when reference is made in this Schedule

to an EEC Method which consists in the transposal of a method developed

by an international organization (e.g. OECD), Member States may accept

that the required information is generated according to the latest version of

that method if at the initiation of the studies the EEC Method has not yet

been updated;

1.4. include, when required by the director, a full description of test guidelines

used, except if they are referred to or described in this Schedule, and a full

description of any deviations from them including a justification, which is

acceptable to the director, for these deviations;

1.5. include a full and unbiased report of the studies conducted as well as full

description of them or a justification, which is acceptable to the director

where

—particular data and information which would not be necessary owing to

the nature of the product or its proposed uses, are not provided,

or

—it is not scientifically necessary, or technically possible to supply infor-

mation and data;

1.6. where relevant, have been generated in accordance with the requirements of

Directive 86/609/EEC.

2.1. Tests and analyses must be conducted in accordance with the principles laid

down in Directive 2004/10/EEC where testing is done to obtain data on the

properties and/or safety with respect to human or animal health or the

environment.

2.2. By way of derogation from point 2.1, the director may provide that tests

and analyses, performed in Malta in order to obtain data on the properties

and/or safety of the substances with respect to honey-bees and beneficial

arthropods other than bees shall be conducted by official or officially-

recognized testing facilities or organizations which satisfy at least the

requirements as set out under points 2.2 and 2.3 of the introduction to

Schedule III.

This derogation applies to trials actually started on or before 31 December

1999.

2.3. By way of derogation from point 2.1, the Director may provide that

supervised residue trials performed in Malta in accordance with the

provisions of Section 6‘Residues in or on treated products, food and

feed’ on plant protection products containing active substances already on

the market two years after notification of the Directive shall be conducted

by official or officially-recognized testing facilities or organizations which

satisfy at least the requirements under points 2.2 and 2.3 of the introduction

to Schedule III.

This derogation applies for supervised residue trials actually started on or

before 31 December 1997.

2.4. By way of derogation from point 2.1, for active substances consisting of

micro-organisms or viruses, tests and analyses done to obtain data on the

properties and/or safety with respect to other aspects than human health,

may have been conducted by official or officially recognised testing

facilities or organisations which satisfy at least the requirements under

points 2.2 and 2.3 of the introduction of Schedule III.

PART A

Chemical substances ( 1 )

1. Identity of the active substance

The information provided must be sufficient to identify with

precision each active substance, to define it in terms of its

specification and to characterize it as to its nature. The information

and data referred to, unless otherwise specified, are required for all

active substances.

1.1.

Applicant (name, address, etc.)

The name and address of the applicant (permanent Community

address) must be provided as must the name, position, telephone and

telefax number of the appropriate person to contact.

Where, in addition, the applicant has an office, agent or represen-

tative in the Member State to which the application for inclusion in

Schedule I is submitted, and if different, in the Rapporteur Member

State appointed by the Commission, the name and address of the

local office, agent or representative must be provided, as must the

name, position, telephone and telefax number of the appropriate

person to contact.

1.2.

Manufacturer (name, address, including location of plant)

The name and address of the manufacturer or manufacturers of the

active substance must be provided as must the name and address of

each manufacturing plant in which the active substance is

manufactured. A contact point (preferably a central contact point, to

include name, telephone and telefax number) must be provided, with

a view to providing updating information and responding to queries

arising, regarding manufacturing technology, processes and the

quality of product (including where relevant, individual batches).

Where following inclusion of the active substances in Schedule I,

there are changes in the location or number of manufac-turers, the

information required must again be notified to the Commission and

the Member States.

1.3.

Common name proposed or ISO-accepted, and synonyms

The ISO common name, or proposed ISO common name and where

relevant, other proposed or accepted common names (synonyms),

including the name (title) of the nomenclature authority concerned,

must be provided.

1.4.

Chemical name (IUPAC and CA nomenclature)

The Chemical name as given in Annex I to Directive 67/548/EEC,

or, if not included in this Directive, in accordance with both IUPAC

and CA nomenclature, must be provided.

( 1 ) Substance within the meaning of the definition of Article 2, point 3 of Directive 414/1991.

1.5.

Manufacturer's development code number(s)

Code numbers used to identify the active substance, and where

available, formulations containing the active substance, during

development work, must be reported. For each code number

reported, the material to which it relates, the period for which it was

used, and the Member States or other countries in which it was used

and is being used, must be stated

1.6.

CAS, EEC and CIPAC numbers (if available)

Chemical Abstracts, EEC (EINECS or ELINCS), and CIPAC

numbers, where they exist, must be reported.

1.7.

Molecular and structural formula, molecular mass

The molecular formula, molecular mass and structural formula of the

active substance, and where relevant, the structural formula of each

stereo and optical isomer present in the active substance, must be

provided.

1.8.

Method of manufacture (synthesis pathway) of the active substance

The method of manufacture, in terms of the identity of the starting

materials, the chemical pathways involved, and the identity of by-

products and impurities present in the final product, must be

provided, for each manufacturing plant. Generally process engi-

neering information is not required.

Where the information provided relates to a pilot plant production

system, the information required must again be provided once

industrial scale production methods and procedures have stabilized.

1.9.

Specification of purity of the active substance in g/kg

The minimum content in g/kg of pure active substance (excluding

inactive isomers) in the manufactured material used for production

of formulated products, must be reported.

Where the information provided relates to a pilot plant production

system, the information required must again be provided to the

Commission and the Member States once industrial scale production

methods and procedures have stabilized, if production changes result

in a changed specification of purity.

1.10.

Identity of isomers, impurities and additives (e.g. stabilizers),

together with the structural formula and the content expressed as

g/kg

The maximum content in g/kg of inactive isomers as well as the ratio

of the content of isomers/diastereo-isomers, where relevant, must be

provided. In addition, the maximum content in g/kg of each further

component other than additives, including by-products, and impu-

rities, must be provided. In the case of additives the content in g/kg

must be provided.

For each component, present in quantities of 1 g/kg or more, the

following information, where relevant, must be provided

—chemical name according to IUPAC and CA nomenclature,

—ISO common name or proposed common name if available,

—CAS number, EEC (EINECS or ELINCS) number, and CIPAC

number if available,

—molecular and structural formula,

—molecular mass, and

—maximum content in g/kg.

Where the manufacturing process is such that impurities and by-

products which are particularly undesirable because of their

toxicological, ecotoxicological or environmental properties could be

present in the active substance, the content of each such compound

must be determined and reported. In such cases, the analytical

methods used and the limits of determination, which must be

sufficiently low, for each compound of concern, must be reported.

Additionally the following information, where relevant, must be

provided

—chemical name according to IUPAC and CA nomenclature,

—ISO common name or proposed common name if available,

—CAS number, EEC (EINECS or ELINCS) number, and CIPAC

number if available,

—molecular and structural formula,

—molecular mass, and

—maximum content in g/kg.

Where the information provided relates to a pilot plant production

system, the information required must again be provided once

industrial scale production methods and procedures have stabilized,

if production changes result in a changed specification of purity.

Where the information provided does not fully identify a component

viz. condensates, detailed information on the composition must be

provided for each such component.

The trade name of components added to the active substance, prior to

manufacture of formulated product, to preserve stability and

facilitate ease of handling, where they are used, must also be

provided. Addi-tionally the following information, where relevant,

must be provided for such additives

—chemical name according to IUPAC and CA nomenclature,

—ISO common name or proposed common name if available,

—CAS number, EEC (EINECS or ELINCS) number, and CIPAC

number if available,

—molecular and structural formula,

—molecular mass, and

—maximum content in g/kg.

For added components, other than active substance and other than

impurities resulting from the manufacturing process, the function of

the component (additive) must be given

—antifoaming agent,

—antifreeze,

—binder,

—other (specify),

—buffer,

—dispersing agent,

—stabilizer.

1.11.

Analytical profile of batches

Representative samples of the active substance must be analysed for

content of pure active substance, inactive isomers, impurities and

additives, as appropriate. The analytical results reported must include

quantitative data, in terms of g/kg content, for all components

present in quantities of more than 1 g/kg and typically should

account for at least 98 % of the material analysed. The actual content

of components which are particularly undesirable because of their

toxi-cological, ecotoxicological or environmental properties, must be

determined and reported. Data reported must include the results of

the analysis of individual samples and a summary of that data, to

show the minimum or maximum and typical content of each relevant

component, as appropriate.

Where an active substance is produced in different plants this

information must be provided for each of the plants separately.

In addition, where available and relevant, samples of the active

substance produced in laboratory scale or pilot production systems,

must be analyzed, if such material was used in generating

toxicological or ecotoxicological data.

2. Physical and chemical properties of the active substance

(i) The information provided, must describe the physical and

chemical properties of active substances and together with

relevant information, must serve to characterize them. In

particular, the information provided must permit

—physical, chemical, and technical hazards associated with

active substances, to be identified,

—classification of active substance as to hazard,

—appropriate restrictions and conditions to be associated with

inclusions in Schedule I to be selected, and

—appropriate risk and safety phrases to be specified.

The information and data referred to are required for all active

substances, except where otherwise specified.

(ii) The information provided, taken together with that provided for

relevant preparations, must permit the physical, chemical

hazards associated with preparations, to be identified, permit

preparations to be classified, and permit establishment that

preparations can be used without unnecessary difficulty, and be

such that exposure of man, animals, and the environment is

minimized, taking account of manner of use.

(iii) The extent to which active substances of which inclusion in

Schedule I is sought, comply with relevant FAO specifications,

must be stated. Divergences from FAO specifications must be

described in detail, and justified.

(iv) In certain specified instances, tests must be conducted using

purified active substance of stated specification. In such cases

the principles of the method(s) of purification must be reported.

The purity of such test material, which must be as high as can be

achieved using the best available technology, must be reported.

A reasoned justification must be provided in cases where the

degree of purity achieved is less than 980 g/kg.

Such justification must demonstrate that all technically feasible

and reasonable possibilities for the production of the pure active

substance have been exhausted.

2.1.

Melting point and boiling point

2.1.1.

The melting point or where appropriate the freezing or solidification

point of purified active substance must be determined and reported

according to EEC method A 1. Measurements should be taken up to

360 o C.

2.1.2.

Where appropriate the boiling point of purified active substances

must be determined and reported according to EEC method A 2.

Measurements should be taken up to 360 o C.

2.1.3.

Where melting point and/or boiling point cannot be determined

because of decomposition or sublimation, the temperature at which

decomposition or sublimation occurs, must be reported.

2.2.

Relative density

In the case of active substances which are liquids or solids, the

relative density of the purified active substance must be determined

and reported according to EEC method A 3.

2.3.

Vapour pressure (in Pa), volatility (e.g. Henry's law constant)

2.3.1.

The vapour pressure of purified active substance must be reported

according to EEC method A 4. Where vapour pressure is less than

10 -5 Pa, the vapour pressure at 20 or 25 o C may be estimated by a

vapour pressure curve.

2.3.2.

In the case of active substances which are solids or liquids, volatility

(Henry's law constant) of purified active substance must be

determined or calculated from its water solubility and vapour

pressure and be reported (in Pa m 3 mol -1 ).

2.4.

Appearance (physical state, colour and odour; if known)

2.4.1.

A description of both the colour, if any, and the physical state of both

the active substance as manufactured and purified active substance,

must be provided.

2.4.2.

A description of any odour associated with the active substance as

manufactured and purfied active substance, noted when handling the

materials in laboratories or production plants, must be reported.

2.5.

Spectra (UV/VIS, IR, NMR, MS), molecular extinction at relevant

wavelengths

2.5.1.

The following specta including a table of signal characteristica

needed for interpretation must be determined and reported: Ultravio-

let/Visible (UV/VIS), infrared (R), nuclear magnetic resonance

(NMR), and mass spectra (MS) of purified active substance and

molecular extinction at relevant wavelengths, must be determined

and reported.

The wavelengths at which UV/visible molecular extinction occurs

are to be determined and reported and must include where

appropriate a wavelength at the highest absorption value above 290

nm.

In the case of active substances which are resolved optical isomers

their optical purity must be measured and reported.

2.5.2.

The UV/visible absorption spectra, IR, NMR and MS spectra, where

necessary for the identification of the impurities considered to be of

toxicological, ecotoxicological or environmental significance must

be determined and reported.

2.6.

Solubility in water including effect of pH (4 to 10) on solubility

The water solubility of purified active substances under atmospheric

pressure must be determined and reported according to EEC method

A 6. These water solubility determinations must be made in the

neutral range (i.e. in distilled water in equilibrium with atmospheric

carbon dioxide). Where the active substance is capable of forming

ions, determinations must also be made in the acidic range (pH 4 to

6) and in the alkaline range (pH 8 to 10), and be reported. Where the

stability of the active substance in aqueous media is such that water

solubility cannot be determined, a justification based on test data

must be provided.

2.7.

Solubility in organic solvents

The solubility of the active substances as manufactured in the

following organic solvents at 15 to 25 o C must be determined and

reported if less than 250 g/kg; the temperature applied must be

specified

—Aliphatic hydrocarbon: preferably n-heptane,

—Aromatic hydrocarbon: preferably xylene,

—Halogenated hydrocarbon: preferably 1,2-dichlorethane,

—Alcohol: preferably methanol or isopropyl alcohol,

—Ketone: preferably acetone,

—Ester: preferably ethyl acetate.

If for a particular active substance, one or more of these solvents is

unsuitable (e.g. reacts with test material), alternative solvents can be

used instead. In such cases, choices made must be justified in terms

of their structure and polarity.

2.8.

Partition coefficient n-octanol/water including effect of pH (4 to 10)

The n-octanol/water partition coefficient of purified active substance

must be determined and reported according to EEC method A 8. The

effect of pH (4 to 10) must be investigated when the substance is

acidic or basic as defined by its pKa value (< 12 for acids, > 2 for

bases).

2.9.

Stability in water, hydrolysis rate, photochemical degradation,

quantum yield and identity of breakdown product(s), dissociation

constant including effect of pH (4 to 9)

2.9.1.

The hydrolysis rate of purified active substances (usually radiola-

belled active substance, > 95 % purity), for each of the pH values 4,

7 and 9, under sterile conditions, in the absence of light, must be

determined and report according to EEC method C 7. For substances

with a low rate of hydrolysis, the rate can be determined at 50 o C, or

another appropriate temperature.

If degradation is observed at 50 o C, degradation rate at another

temperature must be determined, and an Arrhenius plot must be

constructed to permit an estimate to be made of hydrolysis at 20 o C.

The identity of hydrolysis products formed and the rate constantly

observed, must be reported. The estimated DT 50 value must also be

reported.

2.9.2.

For compounds with a molar (decadic) absorption coefficient (e)>10

mol -1 cm -1 ) at a wavelengthλ=290 nm, direct photo-

(1

transformation in purified (e.g. distilled) water at 20 to 25 o C, of

purified active substance usually radio labelled using artificial light

under sterile conditions, if necessary using a solubilizer, must be

determined and reported. Sensitizers such as acetone must not be

used as a cosolvent or solubilizer. The light source must simulate

sunlight and be equipped with filters to exclude radiation at wave-

lengthsλ< 290 nm. The identity of breakdown products formed

which at any time during the study are present in quantities =10 % of

the active substance added, a mass balance to account for at least 90

% of the applied radioactivity, as well as photo-chemical halflife

must be reported.

2.9.3.

Where necessary to investigate direct phototrans-formation, the

quantum yield of direct photodegradation in watermust be

determined and reported, together with calculations to estimate theo-

retical lifetime of the active substance in the top layer of aqueous

systems and the real lifetime of the substance.

The method is described in the FAO Revised Guidelines on Envi-

ronmental Criteria for the Registration of Pesticides.

2.9.4.

Where dissociation in water occurs, the dissociation constant(s) (pKa

values) of the purified active substance must be determined and

reported according to OECD Test Guideline 112. The identity of the

dissociated species formed, based on theoretical considerations, must

be reported. If the active, substance is a salt, the pKa value of the

active principle must be given.

2.10.

Stability in air, photochemical degradation, identity of breakdown

product(s)

An estimation of the photochemical oxidative degradation (indirect

hototransformation) of the active substance, must be submitted.

2.11.

Flammability including auto-flammability

2.11.1.

The flammability of active substances as manufactured, which are

solids, gases, or are substances which evolve highly flammable

gases, must be determined and reported according to EEC method A

10, A 11 or A 12 as as appropriate.

2.11.2.

The auto-flamability of active substances as manufactured must be

determined and reported according to EEC method A 15 or A 16 as

appropriate, and/or, where necessary according to the UN-Bowes-

Cameron-Cage-Test (UN-Recommendations on the Transport of

Dangerous Goods, Chapter 14, No 14.3.4).

2.12.

Flash point

The flash point of active substances as manufactured with a melting

point below 40 o C, must be determined and reported according to

EEC method A 9; only closed cup methods should be used.

2.13.

Explosive properties

The explosive properties of active substances as manufactured, must

be determined and reported according to EEC method A 14 where

necessary.

2.14.

Surface tension

The surface tension has to be determined and reported according to

EEC method A 5.

2.15

Oxidizing properties

The oxidizing properties of active substances as manufactured, must

be determined and reported according to EEC method A 17, except

where examination of its sturctural formula, establishes beyond

reasonable doubt that the active substance is incapable of reacting

exothermically with a combustible material. In such cases, it is

sufficient to provide that information as justification for not deter-

mining the oxidizing properties of the substance.

3. Further information on the active substance

(i) The information provided must describe the intended purposes

for which preparations containing the active substance are used,

or are to be used and the dose and manner of their use or

proposed use.

(ii) The information provided must specify the normal methods and

precautions to be followed, in the handling, storage and

transport of the active substance.

(iii) The studies, data and information submitted, together with other

relevant studies, data and information, must both specify and

justify the methods and precautions to be followed in the event

of fire. The possible products of combustion in the event of fire

should be estimated, based on the chemical structure and the

chemical and physical properties of the active substance.

(iv) The studies, data and information submitted, together with other

relevant studies, data and information, must demonstrate the

suitability of measures proposed for use in emergency situations.

(v) The informaton and data referred to are reqired for all active

substances, except where otherwise specified.

3.1.

Function, e.g. fungicide, herbicide, insecticide, repellant, growth

regulator

The function must be specified from among the following

—acaricide

—bactericide

—fungicide

—herbicide

—insecticide

—molluscicide

—nematicide

—plant growth regulator

—repellant

—rodenticide

—semio-chemicals

—talpicide

—viricide

—other (must be specified)

3.2.

Effects on harmful organisms, e.g. contact poison, inhalation poison,

stomach poison, fungitoxic, etc. systematic or not in plants

3.2.1.

The nature of the effects on harmful organisms must be stated

—contact action

—stomach action

—inhalation action

—fungitoxic action

—fungistatic action

—desiccant

—reproduction inhibitor

—other (must be specified)

3.2.2.

It must be stated whether or not the active substance is translocated in

plants and where relevant whether such translocation is apoplastic,

symplastic or both.

3.3.

Field of use envisaged, e.g. field, protected crops, storage of plant

products, home gardening

The field(s) of use, existing and proposed, for preparations

containing the active substance must be specified from among the

following

—Field use, such as agriculture, horticulture, forestry and viticulture

—Protected crops

—Amenity

—Weed control on non-cultivated areas

—Home gardening

—House plants

—Plant products storage practice

—Other (specify)

3.4.

Harmful organisms controlled and crops or products protected or

treated

3.4.1.

Details of existing and the intended use in terms of crops, groups of

crops, plants, or plant products treated and where relevant protected,

must be provided.

3.4.2.

Where relevant, details of harmful organisms against which

protection is afforded, must be provided.

3.4.3

Where relevant, effects achieved e.g. sprout suppression, retardation

of ripening, reduction in stem length, enhanced fertilization etc.,

must be reported.

3.5.

Mode of action

3.5.1.

To the extent that is has elucidated, a statement must be provided as

to the mode of action of the active substance in terms, where

relevant, of the biochemical and physiological mechanism(s) and

biochemical pathway(s) involved. Where available, the results of

relevant experimental studies must be reported.

3.5.2.

Where it is known that to exert its intended effect, the active

substance must be converted to a metabolite or degradation product

following application or use of preparations containing it, the

following information, cross referenced to and drawing on

information provided in the context of paragraphs 5.6, 5.11, 6.1, 6.2,

6.7, 7.1, 7.2 and 9, where relevant, must be provided for active

metabolite or degradation product

—chemical name according to IUPAC and CA nomenclature,

—ISO common name or proposed common name,

—CAS EEC-number EEC (EINECS or ELINCS) number, and

CIPAC number if available,

—empirical and structural formula, and

—molecular mass.

3.5.3.

Available information relating to the formation of active metabolites

and degradation products, must be provided, to include

—the processes, mechanisms and reactions involved,

—kinetic and other data concerning the rate of conversion and if

known the rate limiting step,

—environmental and other factors effecting the rate and extent of

conversion.

3.6.

Information on the occurrence or possible occurrence of the devel-

opment of resistance and appropriate management strategies

Where available information on possible occurrence of the devel-

opment of resistance or cross-resistance must be provided.

3.7.

Recommended methods and precautions concerning handling,

storage, transport or fire

A safety data sheet pursuant to Article 27 of Council Directive

65/548/EEC ( 1 ) must be provided for all active substances.

3.8.

Procedures for destruction or decontamination

3.8.1.

Controlled incineration

In many cases the preferred or sole means to safely dispose of active

substances, contaminated materials, or contaminated packaging, is

through controlled incineration in a licensed incinerator.

Where the content of halogens of the active substance is greater than

60 %, the pyrolytic behaviour of the active substance under

controlled conditions (including where relevant supply of oxygen

and defined residence time), at 800 o C and the content of polyhalo-

genated dibenzo-p-dioxins and dibenzo-furans in the products of

pyrolysis must be reported. The application must provide detailed

instructions for safe disposal.

3.8.2.

Others

Other methods to dispose of the active substance, contaminated

packaging and contaminated materials, where proposed, must be

fully described. Data must be provided for such methods, to establish

their effectiveness and safety.

3.9.

Emergency measures in case of an accident

Procedures for the decontamination of water in case of an accident

must be provided.

4. Analytical methods

Introduction

The provisions of this section only cover analytical methods required

for post-registration control and monitoring purposes.

For analytical methods used for generation of data as required in this

Directive or for other purposes the applicant has to provide a justi-

fication for the method used; where necessary separate guidance will

be developed for such methods on the basis of the same requirements

as defined for methods for post-registration control and monitoring

purposes.

Descriptions of methods must be provided and include details of

equipment, materials and conditions used.

As far as practicable these methods must employ the simplest

approach, involve the minimum cost, and require commonly

available equipment.

For this section the following applies

Impurities

Any component other than the pure active

substance which is present in the active

substance as manufactured (including non-

active isomers) originating from the

manufacturing process or from degra-

dation during storage,

Relevant impurities

Impurities of toxicological and/or ecotox-

icological or environmental concern,

Significant impurities

Impurities with a content of=1 g/kg in

the active substance as manufactured,

Metabolites

Metabolites include products resulting

from degradation or reaction of the active

substance,

Relevant metabolites

Metabolites of toxicological and/or

ecotoxicological

or

environmental

concern.

On request the following samples must be provided

(i) analytical standards of the pure active substance;

(ii) samples of the active substance as manufactured;

(iii) analytical standards of relevant metabolites and all other

components included in the residue definition;

(iv) if available, samples of reference substances for the relevant

impurities.

4.1.

Methods for the analysis of the active substance as manufactured

For this point the following definitions apply

(i)Specificity

Specificity is the ability of a method to distinguish between the

analyte being measured and other substances.

(ii)Linearity

Linearity is defined as the ability of the method, within a given

range, to obtain an acceptable linear correlation between the

results and the concentration of analyte in samples.

(iii)Accuracy

The accuracy of a method is defined as the degree to which the

determined value of analyte in a sample corresponds to the

accepted reference value (for example ISO 5725).

(iv)Precision

Precision is defined as the closeness of agreement between inde-

pendent test results obtained under prescribed conditions.

Repeatability: Precision under repeatability conditions, i.e.

conditions where independent test results are obtained with the

same method on identical test material in the same laboratory by

the same operator using the same equipment within short

intervals of time.

The reproducibility is not required for the active substance as

manufactured (for definition of reproducibility see ISO 5725).

4.1.1.

Methods, which must be described in full, must be provided for the

determination of pure active substance in the active substance as

manufactured as specified in the dossier submitted in support of

inclusion in Annex I to Directive 91/414/EEC. The applicability of

existing Cipac methods must be reported.

4.1.2.

Methods must also be provided for the determination of significant

and/or relevant impurities and additives (e.g. stabilizers) in the active

substance as manufactured.

4.1.3.

Specificity, linearity, accuracy and repeatability

4.1.3.1.

Specificity of methods submitted, must be demonstrated and reported.

In addition the extent of interference by other substances present in

the active substance as manufactured (e.g. isomers, impurities or

additives), must be determined.

While interferences due to other components may be identified as

systematic errors in the assessment of the accuracy of methods

proposed for the determination of pure active substance in the active

substance as manufactured, an explanation must be provided for any

interference occurring which contributes more than ± 3 % to the total

quantity determined. The degree of interference for methods for the

determination of impurities must also be demonstrated.

4.1.3.2.

The linearity of proposed methods over an appropriate range must be

determined and reported. For the determination of pure active

substance, the calibration range must extend (by at least 20 %) the

highest and lowest nominal content of the analyte in relevant

analytical solutions. Duplicate calibration determinations must be

made at three or more concentrations. Alternatively, five concen-

trations, each as single measurements, are acceptable. Reports

submitted must include the equation of the calibration line and the

correlation coefficient and representative and properly labelled docu-

mentation from the analysis, e.g. chromatograms.

4.1.3.3.

Accuracy is required for methods for the determination of pure active

substance and significant and/or relevant impurities in the active

substance as manufactured.

4.1.3.4.

For the repeatability in the determination of the pure active substance

in principle a minimum of five determinations must be made. The

relative standard deviation (% RSD) must be reported. Outliers iden-

tified through an appropriate method (e.g. Dixons or Grubbs test),

may be discarded. Where outliers have been discarded, that fact must

be clearly indicated. An explanation as to the reason for the

occurrence of individual outliers, must be attempted.

4.2.

Methods for the determination of residues

The methods must be capable of determining the active substance

and/or relevant metabolites. For each method and for each relevant

representative matrix, the specificity, precision, recovery, and limit

of determination must be experimentally determined and reported.

In principle, residue methods proposed should be multi-residue

methods; a standard multi-residue method must be assessed and

reported as to its suitability for residue determination. Where residue

methods proposed are not multi-residue methods, or are not

compatible with such methods, an alternative method must be

proposed. Where this requirement results in an excessive number of

methods for individual compounds, a‘common moiety method’may

be acceptable.

For this section the following definitions apply

(i)Specificity

Specificity is the ability of a method to distinguish between the

analyte being measured and other substances.

(ii)Precision

Precision is defined as the closeness of agreement between inde-

pendent test results obtained under prescribed conditions.

Repeatability: Precision under repeatability conditions, i.e.

conditions where independent test results are obtained with the

same method on identical test material in the same laboratory by

the same operator using the same equipment within short

intervals of time.

Reproducibility: As the definition of reproducibility in relevant

publications (for example, in ISO 5725) is in general not prac-

ticable for residue analytical methods, reproducibility in the

context of this Directive is defined as a validation of repeatability

of recovery, from representative matrices and at representative

levels, by at least one laboratory which is independent from that

which initially validated the study (this independent laboratory

may be within the same company) (independent laboratory

validation).

(iii)Recovery

The percentage of the amount of active substance or relevant

metabolite originally added to a sample of the appropriate matrix

which contains no detectable level of the analyte.

(iv)Limit of determination

The limit of determination (often referred to as limit of quantifi-

cation) is defined as the lowest concentration tested, at which an

acceptable mean recovery is obtained (normally 70 to 110 % with

a relative standard deviation of preferably=20 %; in certain

justified cases lower or higher mean recovery rates as well as

higher relative standard deviations may be acceptable).

4.2.1.

Residues in and/or on plants, plant products, foodstuffs (of plant and

animal origin), feedingstuffs

Methods submitted must be suitable for the determination of all

components included in the residue definition as submitted according

to the provisions of section 6, points 6.1 and 6.2 in order to enable

the Director to determine compliance with established MRL's or to

determine dislodgeable residues.

The specificity of the methods must enable all components included

in the residue definition to be determined, using an additional confir-

matory method if appropriate.

The repeatability must be determined and reported. The replicate

analytical portions for test can be prepared from a common field

treated sample, containing incurred residues. Alternatively the

replicate analytical portions for test can be prepared from a common

untreated sample with aliquots fortified at the required level(s).

The results from an independent laboratory validation must be

reported.

The limit of determination including the individual and mean

recovery must be determined and reported. The overall relative

standard deviation, as well as the relative standard deviation for each

fortification level must be experimentally determined and reported.

4.2.2.

Residues in soil

Methods for analysis of soil for parent compound and/or relevant

metabolites must be submitted.

The specificity of the methods must enable the parent compound

and/or relevant metabolites to be determined, using an additional

confirmatory method if appropriate.

The repeatability, recovery and the limit of determination including

the individual and mean recovery must be determined and reported.

The overall relative standard deviation, as well as the relative

standard deviation for each fortification level must be experimentally

determined and reported.

The proposed limit of determination must not exceed a concentration

which is of concern with regard to exposure of non-target organisms

or because of phytotoxic effects. Normally the proposed limit of

determination should not exceed 0,05 mg/kg.

4.2.3.

Residues in water (including drinking water, ground water and

surface water)

Methods for analysis in water for parent compound and/or relevant

metabolites must be submitted.

The specificity of the methods must enable the parent compound

and/or relevant metabolites to be determined, using an additional

confirmatory method if appropriate.

The repeatability, recovery and the limit of determination including

the individual and mean recovvery must be determined and reported.

The overall relative standard deviation, as well as the relative

standard deviation for each fortification level must be experimentally

determined and reported.

For drinking water the proposed limit of determination must not

exceed 0,1µg/l. For surface water the proposed limit of

determination must not exceed a concentration which has an impact

on non-target organisms deemed to be unacceptable according to the

requirements of Schedule VI.

4.2.4.

Residues in air

Methods for the analysis in air of the active substance and/or

relevant metabolites formed during or shortly after application must

be submitted unless it can be justified that exposure of operators,

workers or bystanders is not likely to occur. The specificity of the

methods must enable the parent compound and/or relevant

metabolites to be determined, using an additional confirmatory

method if appropriate.

The repeatability, recovery and the limit of determination including

the individual and mean recovery must be determined and reported.

The overall relative standard deviation, as well as the relative

standard deviation for each fortification level must be experimentally

determined and reported.

The proposed limit of determination must take into account relevant

health based limit values or relevant exposure levels.

4.2.5.

Residues in body fluids and tissues

Where an active substance is classified as toxic or highly toxic

appropriate analytical methods must be submitted.

The specificity of the methods must enable the parent compound

and/or relevant metabolites to be determined, using an additional

confirmatory method if appropriate.

The repeatability; recovery and the limit of determination including

the individual and mean recovery must be determined and reported.

The overall relative standard deviation, as well as the relative

standard deviation for each fortification level must be experimentally

determined and reported.

5. Toxicological and metabolism studies

Introduction

(i) The information provided, taken together with that provided for

one or more preparations containing the active substance, must be

sufficient to permit an evaluation to be made as to the risks for man,

associated with the handling and use of plant protection products

containing the active substance, and the risk for man arising from

residual traces remaining in food and water. In addition, the

information provided must be sufficient to

—permit a decision to be made as to whether, or not, the active

substance can be included in Schedule I,

— specify appropriate conditions or restrictions to be associated

with any inclusion in Schedule I,

— classify the active substance as to hazard,

— establish a relevant acceptable daily intake (ADI) level for man,

— establish acceptable operator exposure level(s) (AOEL),

— specify the hazard symbols, the indications of danger, and the

risk and safety phrases for the protection of man, animals and the

environment to be included in packaging (containers),

— identify relevant first aid measures as well as appropriate

diagnostic and therapeutic measures to be followed in the event of

poisoning in man, and

— permit an evaluation to be made as to the nature and extent of

the risks for man, animals (species normally fed and kept or

consumed by man) and of the risks for other non-target vertebrate

species.

(ii) There is a need to investigate and report all potentially adverse

effects found during routine toxicological investi-gations

(including effects on organs and special systems such as

immunotoxicity and neurotoxicity) and to undertake and report

such additional studies which may be necessary to investigate the

probable mechanism involved, to establish Noaels (no observed

adverse effect levels), and to assess the significance of these

effects. All available biological data and information which is

relevant to the assessment of the toxicological profile of the

substance tested, must be reported.

(iii) In the context of the influence that impurities can have on

toxicological behaviour, it is essential that for each study

submitted, a detailed description (specification) of the material

used, as mentioned under section 1 point 11 be provided. Tests

should be conducted using active substance of that specification to

be used in the manufacture of preparations to be authorized, except

where radiolabelled material is required or permitted.

(iv) Where studies are conducted using an active substance

produced in the laboratory or in a pilot plant production system,

the studies must be repeated using the active substance as

manufactured, unless it can be justified that the test material used

is essentially the same, for the purposes of toxicological testing

and assessment. In cases of uncertainty, appropriate bridging

studies must be submitted to serve as a basis for a decision as to

the possible need for repetition of the studies.

(v) In the case of studies in which dosing extends over a period,

dosing should preferably be done using a single batch of active

substance if stability permits.

(vi) For all studies actual achieved dose in mg/kg body weight, as

well as in other convenient units, must be reported. Where dosing

via the diet is utilized the test compound must be distributed

uniformly in the diet.

(vii) Where, as a result of metabolism or other processes in or on

treated plants, or as a result of processing of treated products, the

terminal residue (to which consumers or workers as defined in

Schedule III, point 7.2.3 will be exposed) contains a substance

which is not the active substance itself and is not identified as a

metabolite in mammals, it will be necessary to carry out toxicity

studies on these components of the terminal residue unless it can

be demonstrated that consumer or worker exposure to these

substances does not constitute a relevant risk to health.

Toxicokinetic and meta-bolism studies relating to metabolites and

degradation products should only be conducted if toxicity findings

of the metabolite cannot be evaluated by the available results

relating to the active substance.

(viii) The way of administration of the test substance depends on

the main exposure routes. In cases where exposure is mainly by the

gas phase, it can be more appropriate to perform inhalation studies

instead of oral studies.

5.1.

Studies on absorption, distribution, excretion and metabolism in

mammals

Quite limited data, as described below and restricted to one test

species (normally the rat) may be all that is required in this area.

These data can provide information useful in the design and inter-

pretation of subsequent toxicity tests. However, it must be

remembered that information on interspecies differences may be

crucial in extrapolation of animal data to man and information on

percutaneous penetration, absorption, distribution, excretion and

metabolism may be useful in operator risk assessments. It is not

possible to specify detailed data requirements in all areas, since the

exact requirements will be dependant upon the results obtained for

each particular test substance.

Aim of the test

The tests should provide sufficient data to permit

—an evaluation of the rate and extent of absorption,

—the tissue distribution and the rate and extent of excretion of the

test substance and the relevant metabolites,

—the identification of metabolites and the metabolic pathway.

The effect of dose level on these parameters and whether results are

different after single versus repeated doses, should also be inves-

tigated.

Circumstances in which required

A single dose toxicokinetic study in rats (oral route of

administration) in at least two dose levels as well as a repeated dose

toxicokinetic study in rats (oral route of administration) at a single

dose level, must be conducted and reported. It may be necessary in

some cases to perform additional studies on another species (such as

goat or chicken).

Test guideline

Commission Directive 87/302/EEC of 18 November 1987 adapting

to technical progress for the ninth time Council Directive

67/548/EEC on the approximation of laws, regulations and

administrative provisions relating to the classification, packaging and

labelling of dangerous substances ( 1 ), part B, Toxicokinetics.

5.2.

Acute toxicity

The studies, data and information to be provided and evaluated must

be sufficient to permit the identification of effects following a single

exposure to the active substance, and in particular to establish, or

indicate

—the toxicity of the active substance;

—the time course and characteristics of the effects with full details

of behavioural changes and possible gross pathological findings

at post-mortem;

—where possible mode of toxic action; and

—the relative hazard associated with the different routes of

exposure.

While the emphasis must be on estimating the toxicity ranges

involved, the information generated must also permit the active

substance to be classified in accordance with Council Directive

67/548/EEC. The information generated through acute toxicity

testing is of particular value in assessing hazards likely to arise in

accident situations.

5.2.1.

Oral

Circumstances in which required

The acute oral toxicity of the active substance must always be

reported.

Test guideline

The test must be carried out in accordance with the Annex to

Commission Directive 92/69/EEC of 31 July 1992 adapting to

technical progress for the seventeenth time Council Directive

67/548/EEC on the approximation of laws, regulations and adminis-

trative provisions relating to the classification, packaging and

labelling of dangerous substances ( 2 ), Method B1 or B1 bis.

5.2.2.

Percutaneous

Circumstances in which required

The acute percutaneous toxicity of the active substance must always

be reported.

Test guideline

Both local and systemic effects must be investigated. The test must

be carried out in accordance with Directive 92/69/EEC method B3.

5.2.3.

Inhalation

Circumstances in which required

The inhalation toxicity of the active substance must be reported

where the active substance is

—a gas or liquified gas,

—is to be used as a fumigant,

—is to be included in a smoke generating, aerosol or vapour

releasing preparation,

—is to be used with fogging equipment,

—has a vapour pressure > 1 10& minus;2 Pa and is to be included in

preparations to be used in enclosed spaces such as warehouses or

glasshouses,

—is to be included in preparations which are powders containing a

significant proportion of particles of diameter <50µm< (> 1 % on

a weight basis), or

—is to be included in preparations to be applied in a manner which

generates a significant proportion of particles or droplets of

diameter < 50µm (> 1 % on a weight basis).

Test guideline

The test must be carried out in accordance with Directive 92/69/EEC

Method B2.

5.2.4.

Skin irritation

Aim of the test

The test will provide the potential of skin irritancy of the active

substance including the potential reversibility of the effects

observed.

Circumstances in which required

The skin irritancy of the active substance must be determined except

where it is likely, as indicated in the test guideline, that severe skin

effects may be produced or that effects can be excluded.

Test guideline

The acute skin irritation must be carried out in accordance with

Directive 92/69/EEC Method B4.

5.2.5.

Eye irritation

Aim of test

The test will provide the potential of eye irritancy of the active

substance including the potential reversibility of the effects

observed.

Circumstances in which required

Eye irritation tests must be conducted except where it is likely, as

indicated in the test guideline, that severe effects on the eyes may be

produced.

Test guidelines

The acute eye irritation must be determined in accordance with

Directive 92/69/EEC Method B5.

5.2.6.

Skin sensitization

Aim of test

The test will provide sufficient information to assess the potential of

the active substance to provoke skin sensitization reactions.

Circumstances in which required

The test must always be carried out except where the substance is a

known sensitizer.

Test guideline

The test must be carried out in accordance with Directive 92/69/EEC

Method B6.

5.3.

Short-term toxicity

Short-term toxicity studies must be designed to provide information

as to the amount of the active substance that can be tolerated without

toxic effects under the conditions of the study. Such studies provide

useful data on the risks for those handling and using preparations

containing the active substance. In particular, short-term studies

provide an essential insight into possible cumulative actions of the

active substance and the risks to workers who may be intensively

exposed. In addition short-term studies provide information useful in

the design of chronic toxicity studies.

The studies, data and information to be provided and evaluated, must

be sufficient to permit the identification of effects following repeated

exposure to the active substance, and in particular to further

establish, or indicate

—the relationship between dose and adverse effects,

—toxicity of the active substance including where possible the

Noael,

—target organs, where relevant,

—the time course and characteristics of poisoning with full details of

behavioural changes and possible pathological findings at post-

mortem,

—specific toxic effects and pathological changes produced,

—where relevant the persistence and reversibility of certain toxic

effects observed, following discontinuation of dosing,

—where possible, the mode of toxic action, and

—the relative hazard associated with the different routes of

exposure.

5.3.1.

Oral 28-day study

Circumstances in which required

Although it is not mandatory to perform 28-day short term studies,

they can be useful as range finding tests. Where conducted they must

be reported, since the results could be of particular value in the

identification of adaptive responses which can be masked in chronic

toxicity studies.

Test guideline

The test must be carried out in accordance with Directive 92/69/EEC

Method B7.

5.3.2.

Oral 90-day study

Circumstances in which required

The short-term oral toxicity (90 day) of the active substance to both

rat and dog, must always be reported. Where there is evidence that

the dog is significantly more sensitive and where such data are likely

to be of value in extrapolating results obtained to man, a 12-month

toxicity study in dogs must be conducted and reported.

Test guidelines

Directive 87/302/EEC, Part B, sub-chronic oral toxicity test.

5.3.3.

Other routes

Circumstances in which required

For the assessment of operator exposure additional percutaneous

studies may be useful.

For volatile substances (vapour pressure >10 -2 Pascal) expert

judgment is required to decide whether the short term studies have to

be performed by oral or inhalation exposure.

Test guidelines

—28-day dermal: Directive 92/69/EEC Method B9,

—90-day dermal: Directive 87/302/EEC, Part B, sub-chronic dermal

toxicity study,

—28-day inhalation: Directive 92/69/EEC Method B8,

—90-day inhalation: Directive 87/302/EEC, Part B, sub-chronic

inhalation toxicity study.

5.4.

Genotoxicity testing

Aim of the test

These studies are of value in

—the prediction of genotoxic potential

—the early identification of genotoxic carcinogens

—the elucidation of the mechanism of action of some carcinogens

To avoid responses that are artifacts of the test system, excessively

toxic doses must not be used in either in vitro or in vivo assays for

mutagenicity. This approach should be regarded as general guidance.

It is important that a flexible approach is adopted, with selection of

further tests being' dependant upon interpretation of results at each

stage.

5.4.1.

In vitro studies

Circumstances in which required

In vitro mutagenicity tests (bacterial assay for gene mutation, test for

clastogenicity in mammalian cells and test for gene mutation in

mammalian cells) must always be performed.

Test guidelines

Acceptable test guidelines are

Directive 92/69/EEC Method B14—Salmonella Typhimurium

reverse mutation assay

Directive 92/69/EEC Method B10—in vitr omammalian cytogenetic

test

Directive 87/302/EEC, Part B—in vitro mammalian cell gene

mutation test

5.4.2.

In vivo studies in somatic cells

Circumstances in which required

If all the results of the in vitro studies are negative further resting

must be done with consideration of other relevant information

available (including toxicokinetic, toxicodynamic and physico-

chemical data and data on analogous substances). The test can be an

in vivo study or an in vitro study using a different metabolizing

system from that/those previously used.

If the in vitro cytogenetic test is positive, an in vivo test using

somatic cells (metaphase analysis in rodent bone marrow or micro-

nucleus test in rodents) must be conducted.

If either of the in vitro gene mutation tests are positive, an in vivo

test to investigate unscheduled DNA synthesis or a mouse spot test

must be conducted.

Test guidelines

Acceptable test guidelines are

Directive 92/69/EEC Method B12—Micronucleus test,

Directive 87/302/EEC Part B—Mouse spot test,

Directive 92/69/EEC Method B11—In vivo Mammalian Bone-

Marrow cytogenetic test, Chromosomal analysis.

5.4.3.

In vivo studies in germ cells

Circumstances in which required

When any result of an in vivo study in somatic cells is positive, in

vivo testing for germ cell effects may be justified. The necessity for

conducting these tests will have to be considered on a case by case

basis, taking into account information regarding toxicokinetics, use

and anticipated exposure. Suitable tests would need to examine inter-

action with DNA (such as the dominant lethal assay), to look at the

potential for inherited effects and possibly make a quantitative

assessment of heritable effects. It is recognized that in view of their

complexity, the use of quantitative studies would require strong

justification.

5.5.

Long term toxicity and carcinogenicity

Aim of the test

The long-term studies conducted and reported, taken together with

other relevant data and information on the active substance, must be

sufficient to permit the identification of effects, following repeated

exposure to the active substance, and in particular must be sufficient

to

—identify adverse effects resulting from exposure to the active

substance,

—identify target organs, where relevant,

—establish the dose-response relationship,

—identify changes in toxic signs and manifestations observed, and

—establish the Noael.

Similarly, the carcinogenicity studies taken together with other

relevant data and information on the active substance, must be

sufficient to permit the hazards for humans, following repeated

exposure to the active substance, to be assessed, and in particular

must be sufficient

—to identify carcinogenic effects resulting from exposure to the

active substance,

—to establish the species and organ specificity of tumours induced,

—to establish the dose-response relationship, and

—for non-genotoxic carcinogens, to identify the maximum dose

eliciting no adverse effect (threshold dose).

Circumstances in which required

The long-term toxicity and carcinogenicity of all active substances

must be determined. If in exceptional circumstances, it is claimed

that such testing is unnecessary, that claim must be fully justified,

viz.toxicokinetic data demonstrates that absorption of the active

substance does not occur from the gut, through the skin or via the

pulmonary system.

Test conditions

A long-term oral toxicity and carcinogenicity study (two years) of

the active substance must be conducted using the rat as test species;

these studies can be combined.

A carcinogenicity study of the active substance must be conducted

using the mouse as test species.

Where a non-genotoxic mechanism for carcinogenicity is suggested,

a well argued case, supported with relevant experimental data,

including that necessary to elucidate the possible mechanism

involved, must be provided.

While the standard reference points for treatment responses are

concurrent control data, historical control data, may be helpful in the

interpretation of particular carcinogenicity studies. Where submitted,

historical control data should be from the same species and strain,

maintained under similar conditions and should be from

contemporaneous studies. The information on historical control data

provided must include

—identification of species and strain, name of the supplier, and

specific colony identification, if the supplier has more than one

geographical location,

—name of the laboratory and the dates when the study was

performed,

—description of the general conditions under which animals were

maintained, including the type or brand of diet and, where

possible, the amount consumed,

—approximate age, in days, of the control animals at the beginning

of the study and at the time of killing or death,

—description of the control group mortality pattern observed during

or at the end of the study, and other pertinent observations (e.g.

diseases, infections),

—name of the laboratory and the examining scientists responsible

for gathering and interpreting the pathological data from the

study, and

—a statement of the nature of the tumours that may have been

combined to produce any of the incidence data.

The doses tested, including the highest dose tested, must be selected

on the basis of the results of short-term testing and where available at

the time of planning the studies concerned, on the basis of meta-

bolism and toxicokinetic data. The highest dose level in the carcino-

genicity study should elicit signs of minimal toxicity such as slight

depression in body-weight gain (less than 10 %), without causing

tissue necrosis or metabolic saturation and without substantially

altering normal lifespan due to effects other than tumours. If the

long-term toxicity study is carried out separately, the highest dose

level should elicit definite signs of toxicity without causing

excessive lethality. Higher doses, causing excessive toxicity are not

considered relevant to evaluations to be made.

In the collection of data and compilation of reports, incidence of

benign and malignant tumours must not be combined, unless there is

clear evidence of benign tumours becoming malignant with time.

Similarly, dissimilar, un-associated tumours, whether benign or

malignant, occurring in the same organ, must not be combined, for

reporting purposes. In the interests of avoiding confusion, termi-

nology such as that developed by American Society of Toxicologic

Pathologists ( 1 ), or the Hannover Tumour Registry (RENI) should be

used in the nomenclature and reporting of tumours. The system used

must be identified.

It is essential that biological material selected for histopathological

examination includes material selected to provide further

information on lesions identified during gross pathological

examination. Where relevant to the elucidation of mechanism of

action and available, special histological (staining) techniques,

histochemical techniques and electron microscopic examinations,

must be conducted and reported.

Test guideline

The studies must be carried out in accordance with Directive

87/302/EEC, part B, Chronic toxicity test, Carcinogenicity test or

combined chronic toxicity/carcinogenicity test.

( 1 )Standardized System of Nomenclature and Diagnostic Criteria—Guides for Toxicologic Pathology

5.6.

Reproductive toxicity

Adverse reproductive effects are of two main types

—impairment of male or female fertility, and

—impacts on the normal development of progeny (developmental

toxicity).

Possible effects on all aspects of reproductive physiology in both

males and females, as well as possible effects on pre-natal and post-

natal development, must be investigated and reported. If in

exceptional circumstances, it is claimed that such testing is unne-

cessary, that claim must be fully justified.

While the standard reference point for treatment responses are

concurrent control data, historical control data may be helpful in the

interpretation of particular reproductive studies. Where submitted,

historical control data should be from the same species and strain,

maintained under similar conditions and should be from

contemporaneous studies. The information on historical control data

provided must include

—identification of species and strain, name of the supplier, and

specific colony identification, if the supplier has more than one

geographical location,

—name of the laboratory and the dates when the study was

performed,

—description of the general conditions under which animals were

maintained, including the type or brand of diet and, where

possible, the amount consumed,

—approximate age, in days, of the control animals at the beginning

of the study and at the time of killing or death,

—description of the control group mortality pattern observed during

or at the end of the study, and other pertinent observations (e.g.

diseases, infections), and

—name of the laboratory and the examining scientist responsible for

gathering and interpreting the toxicological data from the study.

5.6.1.

Multi-generation studies

Aim of the test

The studies reported, taken together with other relevant data and

information on the active substance, must be sufficient to permit the

identification of effects for reproduction, following repeated

exposure to the active substance, and in particular must be sufficient

—to identify direct and indirect effects on reproduction resulting

from exposure to the active substance,

—to identify any enhancement of general toxic effects (noted during

short-term and chronic toxicity testing),

—to establish the dose-response relationship, to identify changes in

toxic signs and manifestations observed, and

—to establish the Noael.

Circumstances in which required

A reproduction toxicity study in rats over at least two generations

must always be reported.

Test guideline

The tests must be carried out in accordance with Directive

87/302/EEC, Part B, two-generation reproduction toxicity test. In

addition organ weight of reproductive organs must be reported.

Supplementary studies

Where necessary for a better interpretation of the effects on repro-

duction and as far as this information is not yet available it could be

necessary to perform supplementary studies in order to provide the

following information

—separate male and female studies,

—three segment designs,

—dominant lethal assay for male fertility,

—cross-matings of treated males with untreated females and vice

versa,

—effects on spermatogenesis,

—effects on oogenesis,

—sperm motility, mobility and morphology, and

—investigation of hormonal activity.

5.6.2.

Developmental toxicity studies

Aim of the test

The studies reported, taken together with other relevant data and

information on the active substance, must be sufficient to permit

effects on embryonic and foetal development, following repeated

exposure to the active substance, to be assessed, and in particular

must be sufficient

—to identify direct and indirect effects on embryonic and foetal

development resulting from exposure to the active substance,

—to identify any maternal toxicity,

—to establish the relationship between observed responses and dose

in both dam and offspring,

—to identify changes in toxic signs and manifestations observed, and

—to establish the Noael.

Furthermore, the tests will give additional information on any

enhancement of general toxic effects of pregnant animals.

Circumstances in which required

The tests must always be carried out.

Test conditions

Developmental toxicity must be determined both to rat and rabbit by

the oral route. Malformations and variations should be reported sepa-

rately. A glossary of terminology and diagnostic principles for

malformations and variations must be given in the report.

Test guideline

The tests must be carried out in accordance with Directive

87/302/EEC, Part B, teratogenicity test—rodent and non-rodent.

5.7.

Delayed neurotoxicity studies

Aim of the test

The test shall provide sufficient data to evaluate if the active

substance could provoke delayed neurotoxicity after acute exposure.

Circumstances in which required

These studies have to be performed for substances of similar or

related structures to those capable of inducing delayed neurotoxicity

such as organophosphates.

Test guidelines

The test must be carried out in accordance with OECD Guideline

418.

5.8.

Other toxicological studies

5.8.1.

Toxicity studies of metabolites as referred to in the introduction point

(vii)

Supplementary studies, where they relate to substances other than the

active substance, are not a routine requirement.

Decisions as to the need for supplementary studies must be made on

a case by case basis.

5.8.2.

Supplementary studies on the active substance

In certain cases it can be necessary to carry out supplementary

studies to further clarify observed effects. These studies could

include

—studies on absorption, distribution, excretion and metabolism,

—studies on the neurotoxic potential,

—studies on the immunotoxicological potential,

—studies on other routes of administration.

Decisions as to the need for supplementary studies must be made on

a case by case basis, taking into account the results of the available

toxicological and metabolism studies and the most important

exposure routes.

Studies required must be designed on an individual basis, in the light

of the particular parameters to be investigated and the objectives to

be achieved.

5.9.

Medical data

Where available, and without prejudice to the provisions of

Council Directive 98/24/EEC of 7 April 1998 on the protection of

the health and safety of workers from the risks related to chemical

agents at work (fourteenth individual Directive within the meaning

of Article 16(1) of Directive 89/391/EEC), practical data and

information relevant to the recognition of the symptoms of

poisoning, and on the effectiveness of first aid and therapeutic

measures have to be submitted. More specific references to the

investigation for antidotal pharmacology or safety pharmacology

using animals should be provided. Where relevant, the

effectiveness of potential antagonists to poisoning, should be

investigated and reported.

Data and information relevant to the effects of human exposure,

where available and of the necessary quality, are of particular value,

in confirming the validity of extrapolations made and conclusions

reached with respect to target organs, dose-response relationships,

and the reversibility of toxic effects. Such data can be generated

following accidental or occupational exposure.

5.9.1.

Medicinal surveillance on manufacturing plant personnel

Reports of occupational health surveillance programmes, supported

with detailed information on the design of the programme, on

exposure to the active substance and exposure to other chemicals,

must be submitted. Such reports should, where feasible, include data

relevant to the mechanism of action of the active substance. These

reports shall, where available, include data from persons exposed in

manufacturing plants or after application of the active substance

(e.g.: in efficacy trials).

Available information on the sensitization including allergenic

response of workers and others exposed to the active substance, must

be provided, and include where relevant details of any incidence of

hypersensitivity. The information provided should include details of

frequency, level and duration of exposure, symptoms observed and

other relevant clinical information.

5.9.2.

Direct observation, e.g.: clinical cases and poisoning incidents

Available reports from the open literature, relating to clinical cases

and poisoning incidents, where they are from refereed journals or

official reports, must be submitted together with reports of any

follow-up studies undertaken. Such reports should contain complete

descriptions of the nature, level and duration of exposure, as well as

the clinical symptoms observed, first aid and therapeutic measures

applied and measurements and observations made. Summary and

abstract information is not of value.

Where supported with the necessary level of detail, such documen-

tation can be of particular value in confirming the validity of extra-

polations from animal data to man and in identifying unexpected

adverse effects which are specific to humans.

5.9.3.

Observations on exposure of the general population and epidemio-

logical studies if appropriate

Where available, and supported with data on levels and duration of

exposure, and conducted in accordance with recognized standards

( 1 ), epidemiological studies are of particular value and must be

submitted.

5.9.4.

Diagnosis of poisoning (determination of active substance, meta-

bolites), specific signs of poisoning, clinical tests

A detailed description of the clinical signs and symptoms of

poisoning, including the early signs and symptoms and full details of

clinical tests useful for diagnostic purposes, where available, must be

provided and include full details of the time courses involved

relevant to the ingestion, dermal exposure or inhalation of varying

amounts of the active substance.

5.9.5.

Proposed treatment: first aid measures, antidotes, medical treatment

The first aid measures to be used in the event of poisoning (actual

and suspected) and in the event of contamination of eyes must be

provided.

Therapeutic regimes for use in the event of poisoning or contamina-

tion of eyes, including where available the use of antidotes, must be

described in full. Information based on practical experience, where it

exists and is available, in other cases on theoretical grounds, as to the

effectiveness of alternative treatment regimes, where relevant, must

be provided. Contraindications associated with particular regimes,

particularly those relating to ‘general medical problems’and

conditions, must be described.

5.9.6.

Expected effects of poisoning

Where known, the expected effects and the duration of these effects

following poisoning must be described and include the impact of

—the type, level and duration of exposure, or ingestion, and

—varying time periods between exposure, or ingestion, and

commencement of treatment.

5.10.

Summary of mammalian toxicity and overall evaluation

A summary of all data and information provided under paragraphs

5.1 through 5.10, must be submitted, and include a detailed and

critical assessment of those data in the context of relevant evaluative

and decision making criteria and guidelines, with particular reference

to the risks for man and animals that may or do arise, and the extent,

quality and reliability of the data base.

( 1 )Guidelines for Good Epidemiology Practices for Occupational and Environmental Research, developed by the Chemical Manufacturers

Association's Epidemiology Task Group, as part of the Epidemiology Resource and Information Centre (ERIC),Pilot Project, 1991

Where relevant, in the light of findings with respect to the analytical

profile of batches of the active substance (paragraph 1.11) and any

bridging studies conducted (paragraphs 5 (iv)), the relevance of the

data as submitted to the assessment of the toxicological profile of the

active substance as manufactured, must be argued.

On the basis of an assessment of the data base, and the relevant

decision making criteria and guidelines, justifications must be

submitted for the Noaels proposed for each relevant study.

On the basis of these data scientifically reasoned proposals for the

establishment of ADI and AOEL(s) for the active substance must be

submitted.

6. Residues in or on treated products, food and feed

Introduction

(i) The information provided, taken together with that provided for

one or more preparations containing the active substance, must

be sufficient to permit an evaluation to be made as to the risks for

man, arising from residues of the active substance and relevant

metabolites, degradation and reaction products remaining in

food.

In addition, the information provided must be sufficient to

—permit a decision to be made as to whether, or not, the active

substance can be included in Schedule I,

—specify appropriate conditions or restrictions to be associated

with any inclusion in Schedule I.

(ii) A detailed description (specification) of the material used, as

provided under Section 1, point 11 must be provided.

(iii) Studies should be performed according to the guidance available

on regulatory testing procedures for residues of plant protection

products in food .

(iv) Where relevant, data should be analyzed using appropriate

statistical methods. Full details of the statistical analysis should

be reported.

(v) Stability of residues during storage.

If may be necessary to perform studies on the stability of residues

during storage. Provided samples are frozen within generally 24

hours after sampling and unless a compound is otherwise known

to be volatile or labile, data are not normally required for samples

extracted and analysed within 30 days from sampling (six months

in the case of radio-labelled material).

Studies with non-radio-labelled substances should be carried out

with representative substratets and preferably on samples from

treated crops or animals with incurred residues. Alternatively, if

this is not possible, aliquots of prepared control samples should

be spiked with a known amount of chemical before storage under

normal storage conditions.

Where the degradation during storage is significant (more than

30 %) it may be necessary to change the storage conditions or not

to store the samples prior to analysis and repeat and studies

where the unsatisfactory storage conditions were used.

Detailed information with respect to the sample preparation and

storage conditions (temperature and duration) of samples and

extracts must be submitted. Storage stability data using sample

extracts will also be required unless samples are analysed within

24 hours of extraction.

6.1.

Metabolism, distribution and expression of residue in plants

Aim of the tests

The objectives of these studies are

—to provide an estimate of total terminal residues in the relevant

portion of crops at harvest following treatment as proposed,

—to identify the major components of the total terminal residue,

—to indicate the distribution of residues between relevant crops

parts,

—to quantify the major components of the residue and to establish

the efficiency of extraction procedures for these components,

—to decide on the definition and expression of a residue.

Circumstances in which required

These studies must always be performed unless it can be justified

that no residues will remain on plants/plant products which are used

as food or feedingstuffs.

Test conditions

Metabolism studies have to involve crops or categories of crops in

which plant protection products containing the active substance in

question would be used. If a wide range of uses in different crop

categories or in the category fruits is envisaged, studies have to be

carried out on at least three crops unless it can be justified that a

different metabolism is unlikely to occur. In cases where use is

envisaged in different categories of crops, the studies must be repre-

sentative for the relevant categories. For this purpose crops can be

considered as falling into one of five categories: root vegetables,

leafy crops, fruits, pulses and oilseeds, cereals. If studies are

available for crops from three of these categories and the results

indicate that the route of degradation is similar in all three categories

then it is unlikely that any more studies will be needed unless it

could be expected that a different metabolism will occur. The

metabolism studies have also to take into account the different

properties of the active substance and the intended method of

application.

An evaluation of the results from different studies has to be

submitted on the point and path of uptake (e.g. via leaves or roots),

and on the distribution of residues between relevant parts of the crop

at harvest (with particular emphasis on edible parts for man or

animals). If the active substance or relevant metabolites are not taken

up by the crop, this must be explained. Information on the mode of

action and the physico-chemical properties of the active substance

may be helpful in assessing trial data.

6.2.

Metabolism, distribution and expression of residue in livestock

Aim of tests

The objectives of these studies are

—to identify the major components of the total terminal residue in

edible animal products,

—to quantify the rate of degradation and excretion of the total

residue in certain animal products (milk or eggs) and excreta,

—to indicate the distribution of residues between relevant edible

animal products,

—to quantify the major components of the residue and to show the

efficiency of extraction procedures for these components,

—to generate data from which a decision on the need for livestock

feeding studies as provided for in point 6.4 can be made,

—to decide on the definition and expression of a residue.

Circumstances in which required

Metabolism studies on animals, such as lactating ruminants (e.g. goat

or cow) or laying poultry, are only required when pesticide use may

lead to significant residues in livestock feed (=0,1 mg/kg of the total

diet as received, except special cases e.g. active substances which

accumulate). Where it becomes apparent that metabolic pathways

differ significantly in the rat as compared to ruminants a pig study

must be conducted unless the expected intake by pigs is not

significant.

6.3.

Residue trials

Aim of the tests

The objectives of these studies are

—to quantify the highest likely residue levels in treated crops at

harvest or outloading from store following the propopsed good

agricultural practice (GAP),

and

—to determine, when appropriate, the rate of decline of plant

protection product deposits.

Circumstances in which required

These studies must always be performed where the plant protection

product will be applied to plants/plant products which are used as

food or feedingstuffs or where residues from soil or other substrates

can be taken up by such plants except where extrapolation from

adequate data on another crop is possible.

Residue trial data shall be submitted in the Schedule II dossier for

those uses of plant protection products for which authorization is

sought at the moment of introduction of a dossier for inclusion of the

active substance in Schedule I.

Test conditions

Supervised trials should corrspond to proposed critical GAP. The test

conditions must take into account the highest residues which may

reasonably arise (e.g. maximum number of proposed applications,

use of the maximum envisaged quantity, shortest pre-harvest

intervals, withholding periods or storage periods) but which remain

represen-tative of the realistic worst case conditions in which the

active substance would be used.

Sufficient data must be generated and submitted to confirm that

patterns determined hold for the regions and the range of conditions,

likely to be encountered in the regions concerned for which its use is

to be recommended.

When establishing a supervised trial programme, normally factors

such as climatic differences existing between production areas,

differences in production methods (e.g. outdoor versus glasshouse

uses), seasons of production, type of formulations, etc. should be

taken into account.

In general, for a comparable set of conditions, trials should be

carried out over a minimum of two growing seasons. All exceptions

should be fully justified.

The precise number of trials necessary is difficult to determine in

advance of a preliminary evaluation of the trial results. Minimum

data requirements only apply where comparability can be established

between production areas, e.g. concerning climate, methods and

growing seasons of production, etc. Assuming all other variables

(climate, etc.) are comparable, a minimum of eight trials represen-

tative of the proposed growing area is required for major crops. For

minor crops normally four trials representative of the proposed

growing area are required.

Due to the inherently higher level of homogeneity in residues arising

from post-harvest treatments or protected crops, trials from one

growing season will be acceptable. For post-harvest treatments, in

principle a minimum of four trials are required, carried out

preferably at different locations with different cultivars. A set of

trials has to be carried out for each application method and store type

unless the worst case residue situation can be clearly identified.

The number of studies per growing season to be performed can be

reduced if it can be justified that the residue levels in plants/plant

products will be lower than the limit of determination.

Where a significant part of the consumable crop is present at the time

of application, half of the supervised residue trials reported should

include data to show the effect of time on the level of residue present

(residue decline studies) unless it can be justified that the

consumable crop is not affected by the application of the plant

protection product under the proposed conditions of use.

6.4.

Livestock feeding studies

Aim of the tests

The objective of these studies is to determine the residue in products

of animal origin which will result from residues in feedingstuffs or

fodder crops.

Circumstances in which required

Feeding studies are only required

—when significant residues (=0,1 mg/kg of the total diet as

received, except special cases, such as active substances which

accumulate) occur in crops or part of the crop (e.g. trimmings,

waste) fed to animals, and

—when metabolism studies indicate that significant residues

(0,01 mg/kg or above the limit of determination if this would be

higher than 0,01 mg/kg) may occur in any edible animal tissue

taking into account the residue levels in potential feeding-stuffs

obtained at the 1 dose rate.

Where appropriate separate feeding studies for lactating ruminant

and/or laying poultry should be submitted. Where it appears from the

metabolism studies submitted in accordance with the provisions of

point 6.2 that metabolic pathways differ significantly in the pig as

compared to ruminants, a pig feeding study must be conducted

unless the expected intake by pigs is not significant.

Test conditions

In general, the feed is administered in three dosages (expected

residue level, three to five times, and 10 times the expected residue

level). When setting the 1 dose, a theoretical feed ration must be

compiled.

6.5.

Effects of industrial processing and/or household preparations

Circumstances in which required

The decision as to whether it is necessary to carry out processing

studies will depend on

—the importance of a processed product in the human or animal diet,

—the level of residue in the plant or plant product to be processed,

—the physico-chemical properties of the active substance or relevant

metabolites, and

—the possibility that degradation products of toxicological signif-

icance may be found after processing of the plant or plant

product.

Processing studies are not normally necessary if no significant or no

analytically determinable residues occur in the plant or plant product

which would be processed, or if the total theoretical maximum daily

intake (TMDI) is less than 10 % of the ADI. In addition, processing

studies are not normally required for plants or plant products mostly

eaten raw except for those with inedible portions such as citrus,

banana or kiwi fruit where data on the distribution of the residue in

peel/pulp may be required.

‘Significant residues’generally refer to residues above 0,1 mg/kg. If

the pesticide concerned has a high acute toxicity and/or a low ADI,

consideration must be given to conducting processing studies for

determinable residues below 0,1 mg/kg.

Studies on the effects on the nature of the residue are not normally

required where only simple physical operations, not involving a

change in temperature of the plant or the plant product, are involved

such as washing, trimming or pressing.

6.5.1.

Effects on the nature of the residue

Aim of the tests

The objective of these studies is to establish whether or not

breakdown or reaction products arise from residues in the raw

products during processing which may require a separate risk

assessment.

Test conditions

Depending upon the level and chemical nature of the residue in the

raw commodity, a set of representative hydrolysis situations (simu-

lating the relevant processing operations) should be investigated,

where appropriate. The effects of process other than hydrolysis, may

also have to be investigated, where the properties of the active

substance or metabolites indicate that toxicologically significant

degradation products may occur as a result of these processes. The

studies are normally conducted with a radio-labelled form of the

active substance.

6.5.2.

Effects on the residue levels

Aim of the tests

The main objectives of these studies are

—to determine the quantitative distribution of residues in the various

intermediate and end products, and to estimate transfer factors,

—to enable a more realistic estimate to be made of dietary intake of

residues.

Test conditions

Processing studies should represent household processing and/or

actual industrial processes.

In the first instance it is usually only necessary to carry out a core set

of‘balance studies’representative of the common processes relevant

to the plants or plant products containing significant residues. Justi-

fication should be given for the selection made of these

representative process(es). The technology to be used in processing

studies should always correspond as closely as possible to the actual

conditions that are normally used in practice. A balance sheet should

be made in which the mass balance of residues in all intermediate

and end products is investigated. In drawing up such a balance sheet

any concentrations or reductions in residues in individual products

can be recognized and the corresponding transfer factors can also be

determined.

If the processed plant products play an important part in the diet, and

if the‘balance study’indicates that a significant transfer of residue

into the processed products could occur, then three‘follow-up

studies’to determine residue concentration or dilution factors must be

carried out.

6.6.

Residues in succeeding crops

Aim of the test

The objective of these studies is to permit an evaluation of possible

residues in succeeding crops.

Circumstances in which required

Where data generated in accordance with Schedule II, Section 7,

point 7.1 or Schedule III, Section 9, point 9.1, shows that significant

residues (> 10 % of the applied active substance as a total of

unchanged active substance and its relevant metabolites or

degradation products) remain in soil or in plant materials, such as

straw or organic material up to sowing or planting time of possible

succeeding crops, and which could lead to residues above the limit of

determination in succeeding crops at harvest, consideration should

be given to the residue situation. This should include consideration

of the nature of the residue in the succeeding crops and involve at

least a theoretical estimation of the level of these residues. If the

likelihood of residues in succeeding crops can not be excluded,

metabolism and distribution studies should be carried out, if

necessary followed by field trials.

Test conditions

If a theoretical estimation of residues in succeeding crops is done,

full details and a justification shall be be given.

Metabolism and distribution studies and field trials, if necessary,

shall be carried out on representative crops chosen to represent

normal agricultural practice.

6.7.

Proposed maximum residue levels (MRLs) and residue definiton

A full justification for the proposed MRLs must be provided,

including, where relevant, full details of the statistical analysis used.

When judging which compounds are to be included in the residue

definition, account has to be taken of the toxicological significance

of the compounds, amounts likely to be present and the practicality

of the analytical methods proposed for post-registration control and

monitoring purposes.

6.8.

Proposed pre-harvest intervals for envisaged uses, or withholding

periods or storage periods, in the case of post-harvest uses

A full justification for the proposals must be provided.

6.9.

Estimation of the potential and actual exposure through diet and

other means

Consideration will be given to the calculation of a realistic prediction

of dietary intake. This may be done in a step-wise fashion leading to

an increasingly realistic predictions of intake. Where relevant, other

sources of exposure such as residues arising from the use of

medicines or veterinary drugs have to be taken into acocunt.

6.10.

Summary and evaluation of residue behaviour

A summary and evaluation of all data presented in this Section

should be carried out according to the guidance given by the

competent authority concerning the format of such summaries and

evaluations. It should include a detailed and critical assessment of

those data in the context of relevant evaluative and decision-making

criteria and guidelines, with particular reference to the risks for man

and animals that may or do arise, and the extent, quality and

reliablity of the data base.

In particular, the toxicological significance of any non-mammalian

metabolites must be addressed.

A schematic diagram should be prepared of the metabolic pathway in

plants and animals with a brief explanation of the distribution and

chemical changes involved.

7. Fate and behaviour in the environment

Introduction

(i) The information provided, taken together with that for one or

more preparations containing the active substance, must be

sufficient to pemit an assessment of the fate and behaviour of the

active substance in the environment, and of the non-target species

likely to be at risk from exposure to the active substance, its

metabolites, degradation and reaction products, where they are of

toxicological or environmental significance.

(ii) In particular, the information provided for the active substance,

together with other relevant information, and that provided for

one or more preparations containing it, should be sufficient to

—decide whether, or not, the active substance can be included in

Schedule I,

—specify appropriate conditions or restrictions to be associated

with any inclusion in Schedule I,

—classify the active substance as to hazard;

—specify the hazard symbols, the indications of danger, and

relevant risk and safety phrases for the protection of the envi-

ronment, which are to be included on packaging (containers),

—predict the disribution, fate, and behaviour in the environment

of the active substance and relevant metabolites, degradation

and reaction products as well as the times courses involved,

—identify non-target species and populations for which hazards a

rise because of potential exposure, and

—identify measures necesary to minimize contamination of the

environment and impact on non-target species.

(iii) A detailed description (specification) of the material used, as

provided for under Section 1, point 11 must be provided. Where

testing is done using active substance the material used should be

of that specification that will be used in the manu-facture of

preparations to be authorized except where radio-labelled

material is used.

Where studies are conducted using active substance produced in

the laboratory or in a pilot plant production system, the studies

must be repeated using active substance as manufactured, unless

it can be justified that the test material used is essentially the

same for the purposes of environmental testing and assessment.

(iv) Where radio-labeled test material is used, radio-labels should be

positioned at sites (one or more as necessary), to facilitate eluci-

dation of metabolic and degradative pathways and to facilitate

investigation of the distribution of the active substance and of its

metabolite, reaction and degradation products in the environ-

ment.

(v) It may be necessary to conduct separate studies for metabolites,

degradation or reaction products, where these products can

constitute a relevant risk to non-target organisms or to the quality

of water, soil and air and where their effects cannot be evaluated

by the available results relating to the active substance. Before

such studies are performed the information from the

Sections 5 and 6 has to be taken into account.

(vi) Where relevant, tests should be designed and data analysed using

appropriate statistical methods.

Full details of the statistical anaylsis should be reported (e.g. all

point estimates should be given with confidence intervals, exact

p-values should be given rather than stating significant/non

significant).

7.1.

Fate and behaviour in soil

All relevant information on the type and the properties of the soil

used in the studies, including pH, organic carbon content, cation

exchange capacity, particle size distribution and water holding

capacity, particle size distribution and water holding capacity at pF =

0 and pF = 2,5 has to be reported in accordance with relevant ISO or

other international standards.

The microbial biomass of soils used for laboratory degradation

studies must be determined just prior to the commencement and at

the end of the study.

It is recommended to use as much as possible the same soils

throughout all laboratory soil studies.

The soils used for degradation or mobility studies must be selected

such that they are representative of the range of soils typical of the

various Community regions where use exists or is anticipated, and be

such that

—they cover a range of organic carbon content, particle size distri-

bution and pH values; and

—where on the basis of other information, degradation or mobility

are expected to be pH dependent (e.g. solubility and hydrolysis

rate—paragraphs 2.7 and 2.8), they cover the following pH

ranges

—4,5 to 5,5

—6 to 7, and

—8 (approximately).

Soils used must, wherever possible, be freshly sampled. If use of

stored soils is unavoidable, storage should be properly carried out for

a limited time under defined and reported conditions. Soils stored for

longer periods of time can only be used for adsorption/desorption

studies.

The soil chosen to begin studying should not have extreme charac-

teristics with respect to parameters such as particle size distribution,

organic carbon content and pH.

Soils should be collected and handled in accordance with ISO

10381-6(Soil quality—Sampling—Guidance on the collection,

handling and storage of soil for the assessment of microbial

processes in the laboratory). Any deviations must be reported and

justified.

Field studies should be carried out in conditions as close to normal

agricultural practice as possible on a range of soil types and climatic

conditions representative of the area(s) of use. Weather conditions

shall be reported in cases where field studies are conducted.

7.1.1.

Route and rate of degradation

7.1.1.1.

Route of degradation

Aim of the tests

The data and information provided, together with other relevant data

and information, should be sufficient to

—identify, where feasable, the relative importance of the types of

process involved (balance between chemical and biological

degra-dation),

—identify the individual components present which at any time

account for more than 10 % of the amount of active substance

added, including, where feasible, non-extractable residues,

—identify where possible also individual components present which

account for less than 10 % of the amount of active substance

added,

—establish the relative proportions of the components present (mass

balance), and

—permit the soil residue of concern and to which non-target species

are or may be exposed, to be defined.

Where a reference is made to non-extractable residues these are

defined as chemical species originating from pesticides used

according to good agricultural practice that cannot be extracted by

methods which do not significantly change the chemical nature of

these residues. These non-extractable residues are not considered to

include fragments through metabolic pathways leading to natural

products.

7.1.1.1.1. Aerobic degradation

Circumstances in which required

The degradation pathway or pathways must always be reported

except where the nature and manner of use of preparations

containing the active substance, preclude soil contamination such as

uses on stored products or wound healing treatments for trees.

Test conditions

The degradation pathway or pathways must be reported for one soil.

Results obtained must be presented in the form of schematic

drawings showing the pathways involved, and in the form of balance

sheets which show the distribution of radio-label as a function of

time, as between

—active substance,

—CO 2 ,

—volatile compounds other than CO 2 ,

—individual identified transformation products,

—extractable substances not identified, and

—non-extractable residues in soil.

The investigation of degradation pathways must include all feasible

steps to characterise and quantify non-extractable residues formed

after 100 days when exceeding 70 % of the applied dose of the active

substance. The techniques and methodologies applied are best

selected on a case-by-case basis. A justification must be provided

where the compounds involved are not characterized.

The duration of the study is normally 120 days, except where after a

shorter period the levels of non-extractable residues and CO 2 are such

that they can be extrapolated in a reliable way to 100 days.

Test guideline

Setac—Procedures for assessing the environmental fate and

ecotoxicity of pesticides ( 1 ).

( 1 ) Society of Environmental Toxicology and Chemistry (SETAC), 1995. Procedures for

assessing the environmental fate and ecotoxicity of pesticides, ISBN 90-5607-002-9.

7.1.1.1.2. Supplementary studies

—Anaerobic degradation

Circumstances in which required

An anaerobic degradation study must be reported unless it can be

justified that exposure of the plant protection products containing

the active substance to anaerobic conditions is unlikely to occur.

Test conditions and test guideline

The same provisions as provided for under the corresponding

paragraph of point 7.1.1.1.1 apply.

—Soil photolysis

Circumstances in which required

A soil photolysis study must be reported unless it can be justified

that deposition of the active substance at the soil surface is

unlikely to occur.

Test guideline

Setac—Procedures for assessing the Environmental fate and

ecotoxicity of pesticides.

7.1.1.2.

Rate of degradation

7.1.1.2.1. Laboratory studies

Aim of the tests

The soil degradation studies should provide best possible estimates

of the time taken for degradation of 50 % and 90 % (DT 50lab and

DT 90lab ), of the active substance, and of relevant metabolites, degra-

dation and reaction products under laboratory conditions.

—Aerobic degradation

Circumstances in which required

The rate of degradation in soil must always be reported, except

where the nature and manner of use of plant protection products

containing the active substance preclude soil contamination such

as uses on stored products or wound healing treatments for trees.

Test conditions

The rate of aerobic degradation of the active substance in three

soil types additional to that referred to in paragraph 7.1.1.1.1.

must be reported.

In order to investigate the influence of temperature on degra-

dation, one additional study at 10 o C has to be performed on one

of the soils used for the investigation of degradation at 20 o C until

a validated Community calculation model for the extrapolation of

degradation rates at low temperatures is available.

The duration of the study is normally 120 days except if more

than 90 % of the active substance is degraded before that period

expires.

Similar studies for three soil types must be reported for all

relevant metabolites, degradation and reaction products which

occur in soil and which at any time during the studies account for

more than 10 % of the amount of active substance added, except

where their DT 50 values were able to be determined from the

results of the degradation studies with the active substance.

Test guideline

Setac—Procedures for assessing the environmental fate and

ecotoxicity of pesticides.

—Anaerobic degradation

Circumstances in which required

The rate of anaerobic degradation of the active substance must be

reported where an anaerobic study has to be performed according

to point 7.1.1.1.2.

Test conditions

The rate of anaerobic degradation of the active substance must be

carried out in the soil used in the anaerobic study performed

according to point 7.1.1.1.2.

The duration of the study is normally 120 days except if more

than 90 % of the active substance is degraded before that period

expires.

Similar studies for one soil must be reported for all relevant

metobolites, degradation and reaction products which occur in

soil and which at any time during the studies account for more

than 10 % of the amount of active substance added, except where

their DT 50 values were able to be determined from the results of

the degradation studies with the active substance.

Test guideline

Setac—Procedures for assessing the environmental fate and

ecotoxicity of pesticides.

7.1.1.2.2. Field studies

—Soil dissipation studies Aim of the

test

The soil dissipation studies should provide estimates of the time

taken for dissipation of 50 % and 90 % (DT 50f and DT 90f ), of the

active substance under field conditions. Where relevant, infor-

mation on relevant metabolites, degradation and reaction

products must be reported.

Circumstances in which required

The tests have to be conducted in those conditions where DT 50lab

determined at 20 o C and at a moisture content of the soil related to

a pF value of 2 to 2,5 (suction pressure) is greater than 60 days.

Where plant protection products containing the active substance

are intended to be used in cold climatic conditions, the tests have

to be conducted where DT 50lab , determined at 10 o C and at a

moisture content of the soil related to a pF value of 2 to 2,5

(suction pressure) is greater than 90 days.

Test conditions

Individual studies on a range of representative soils (normally

four different types) must be continued until > 90 % of the

amount applied have dissipated. The maximum duration of the

studies is 24 months.

Test guideline

SETAC—Procedures for assessing the environmental fate and

ecotoxicity of pesticides.

—Soil residue studies Aim of the

test

Soil residue studies should provide estimates of the soil residue

levels at harvest or at time of cowing or planting succeeding

crops.

Circumstances in which required

Soil residue studies must be reported where DT 50lab is greater than

one-third of the period between the application and harvest and

where absorption by the succeeding crop is possible, except

where soil residues at sowing or planting of a succeeding crop

can be reliably estimated from the data of the soil dissipation

studies or where it can be justified that these residues can not be

phytotoxic to or leave unacceptable residues in rotational crops.

Test conditions

Individual studies must be continued until harvest or time of

sowing or planting succeeding crops, unless > 90 % of the

amount applied have dissipated.

Test guideline

SETAC—Procedures for assessing the environmental fate and

ecotoxicity of pesticides.

—Soil accumulation studies Aim of the

tests

The tests should provide sufficient data to evaluate the possibility

of accumulation of residues of the active substance and of

relevant metabolites, degradation and reaction products.

Circumstances in which required

Where on the basis of soil dissipation studies it is established that

DT 90f > one year and where repeated application is envisaged,

whether in the same growing season or in succeeding years, the

possibility of accumulation of residues in soil and the level at

which a plateau concentration is achieved must be investigated

except where reliable information can be provided by a model

calculation or another appropriate assessment.

Test conditions

Long term field studies must be done on two relevant soils and

involve multiple applications.

Before performing these studies the applicant shall seek the

agreement of the competent authorities on the type of study to be

performed.

7.1.2.

Adsorption and desorption

Aim of the test

The data and information provided, together with other relevant data

and information, should be sufficient to establish the absorption

coef-ficient of the active substance and of relevant metabolites,

degra-dation and reaction products.

Circumstances in which required

The studies must always be reported except where the nature and

manner of use of preparations containing the active substance,

preclude soil contamination such as uses on stored products or

wound healing trees.

Testo conditions

Studies on the active substance must be reported for four soil types.

Similar studies, for at least three soil types, must be reported for all

relevant metabolites, degradation and reaction products which in soil

degradation studies account at any time for more than 10 % of the

amount of active substance added.

Test guideline

OECD method 106

7.1.3.

Mobility in the soil

7.1.3.1.

Column leaching studies

Aim of the test

The test should provide sufficient data to evaluate the mobility and

leaching potential of the active substance and if possible of relevant

metabolities, degradation and reaction products.

Circumstances in which required

Studies in four soils must be carried out where in the absorption and

desorption studies provided for under point 7.1.2 it is not possible to

obtain reliable absorption coefficient values.

Test guideline

SETAC—Procedures for assessing the environmental fate and

ecotoxicity of pesticides.

7.1.3.2.

Aged residue column leaching

Aim of the test

The test should provide sufficient data to estimate the mobility and

leaching potential of relevant metabolites, degradation and reaction

products.

Circumstances in which required

The studies must be performed except

—where the nature and manner of use of preparations containing the

active substance, preclude soil contamination such as uses on

stored products or wound healing treatments for trees, or

—where a separate study for the metabolite, degradation or reaction

product in accordance to point 7.1.2 or 7.1.3.1 was performed.

Test conditions

The period(s) of ageing should be determined from inspection of the

degradation patterns of active substance and metabolites to ensure

that a relevant spectrum of metabolites is present at the time of

leaching.

Test guideline

SETAC—Procedures for assessing the environmental fate and

ecotoxicity of pesticides.

7.1.3.3.

Lysimeter studies or field leaching studies

Aim of the tests

The test should provide data on

—the mobility in soil,

—the potential for leaching to ground water,

—The potential distribution in soil.

Circumstances in which requried

Expert judgement will be necessary to decide whether lysimeter

studies or field leaching studies should be carried out, taking into

account the results of degradation and other mobility studies and the

predicted environmental concentrations in groundwater (PEC GW ),

calculated in accordance with the provisions of Schedule III, Section

9. The type and conditions of the study to be conducted should be

discussed with the competent authorities.

Test conditions

Great care is necessary in design of both experimental installations

and individual studies, to ensure that results obtained can be used for

assessment purposes. Studies should cover the realistic worst case

situation, taking into account the soil type, climatic conditions, the

application rate and the frequency and period of application.

Water percolating from soil columns must be analyzed at suitable

intervals, while residues in plant material must be determined at

harvest. Residues in the soil profile in at least five layers must be

determined on termination of experimental work. Intermediate

sampling must be avoided, since removal of plants (except for

harvesting according to normal agricultural practice) and soil cross

influences the leaching process.

Precipitation, soil and air temperatures have to be recorded at regular

intervals (at least on a weekly base).

—Lysimeterstudies

Test conditions

The minimal depth of the lysimeters should be 100 cm; their

maximal depth should be 130 cm. The soil cross must be undis-

turbed. Soil temperatures must be similar to those pertaining in

the field. Where necessary, supplementary irrigation must be

provided to ensure optimal plant growth and to ensure that the

quantity of infiltration water is similar to that in the regions for

which authorization is sought. When during the study the soil has

to be disturbed for agricultural reasons it must not be disturbed

deeper than 25 cm.

—Field leaching

studies

Test

conditions

Information on the groundwater table in the experimental fields

must be submitted. If soil cracking is observed during the study

this must be fully described.

Great attention should be given to the number and the location of

water collection devices. The placement of these devices in the

soil should not result in preferential flow paths.

Test guideline

SETAC—Procedures for assessing the environmental fate and

ecotoxicity of pesticides.

7.2.

Fate and behaviour in water and air

Aim of the tests

The information and data provided, taken together with that provided

for one or more preparations containing the active substance, and

other relevant information, should be sufficient to establish, or

permit estimation of

—persistence in water systems (bottom sediment and water,

including suspended particles),

—the extent to which water, sediment organisms and air are at risk,

—potential for contamination of surface water and groundwater.

7.2.1.

Route and rate of degradation in aquatic systemes (as far as not

covered by point 2.9)

Aim of the tests

The data and information provided, together with other relevant data

and information, should be sufficient to

—identify the relative importance of the types of processes involved

(balance between chemical and biological degradation),

—where possible, identify the individual components present,

—establish the relative proportions of the components present and

their distribution as between water, including suspended

particles, and sediment, and

—permit the residue of concern and to which non-target species are

or may be exposed, to be defined.

7.2.1.1.

Hydrolytic degradation

Circumstances in which required

The test must always be performed for relevant metabolites, degra-

dation and reaction products which account at any time for more

than 10 % of the amount of active substance added unless sufficient

information on their degradation is available from the test performed

in accordance with point 2.9.1.

Test conditions and test guideline

The same provisions as provided under the corresponding paragraphs

of point 2.9.1 apply.

7.2.1.2.

Photochemical degradation

Circumstances in which required

The test must always be performed for relevant metabolites, degra-

dation and reaction products which account at any time for more

than 10 % of the amount of active substance added unless sufficient

information on their degradation is available from the test performed

in accordance with points 2.9.2 and 2.9.3.

Test conditions and test guideline

The same provisions as provided under the corresponding paragraphs

of points 2.9.2 and 2.9.3 apply.

7.2.1.3.

Biological degradation

7.2.1.3.1.‘Ready biodegradability’

Circumstances in which required

The test must always be performed unless it is not required under the

provisions of Annex VI to Directive 67/548/EEC for the

classification of the active substance.

Test guideline

EEC method C4.

7.2.1.3.2. Water/sediment study

Circumstances in which required

The test must be reported unless it can be justified that

contamination of surface water will not occur.

Test guideline

SETAC—Procedures for assessing the environmental fate and

ecotoxicity of pesticides.

7.2.1.4.

Degradation in the saturated zone

Circumstances in which required

Transformation rates in the saturated zone of active substances and

of relevant metabolites, degradation and reaction products can

provide useful information on the fate of these substances in the

groundwater.

Test conditions

Expert judgement is required to decide whether this information is

necessary. Before performing these studies the applicant shall seek

the agreement of the competent authorities on the type of study to be

performed.

7.2.2.

Route and rate of degradation in air (as far as not covered by point

2.10)

Guidance under development.

7.3.

Definition of the residue

In the light of the chemical composition of residues occurring in soil,

water or air, resulting from use, or proposed use, of a plant

protection product containing the active substance a proposal for the

definition of the residue must be submitted, taking account of both

the levels found and their toxicological and environmental

significance.

7.4.

Monitoring data

Available monitoring data concerning fate and behaviour of the

active substance and relevant metabolites, degradation and reaction

products must be reported.

8. Ecotoxicological studies

Introduction

(i) The information provided, taken together with that for one or

more preparations containing the active substance, must be

sufficient to permit an assessment of the impact on non-target

species (flora and fauna), likely to be at risk from exposure to the

active substance, its metabolites, degradation and reaction

products, where they are of environmental significance. Impact

can result from single, prolonged or repeated exposure and can

be reversible or irreversible.

(ii) In particular, the information provided for the active substance,

together with other relevant information, and that provided for

one or more preparations containing it, should be sufficient to

—decide whether, or not, the active substance can be included in

Schedule I,

—specify appropriate conditions or restrictions to be associated

with any inclusion in Schedule I,

—permit an evaluation of short- and long-term risks for non-

target species—populations, communities, and processes— as

appropriate,

—classify the active substance as to hazard,

—specify the precautions necessary for the protection of non-

target species, and

—specify the hazard symbols, the indications of danger, and

relevant risk and safety phrases for the protection of the envi-

ronment, to be mentioned on packaging (containers).

(iii) There is a need to report all potentially adverse effects found

during routine ecotoxicological investigations and to undertake

and report, where required by the competent authorities, such

additional studies which may be necessary to investigate the

probable mechanisms involved and assess the significance of

these effects. All available biological data and information which

is relevant to the assessment of the ecotoxicological profile of the

active substance must be reported.

(iv) The information on fate and behaviour in the environment,

generated and submitted in accordance with points 7.1 to 7.4, and

on residue levels in plants generated and submitted in accordance

with point 6 is central to the assessment of impact on non-target

species, in that together with information on the nature of the

preparation and its manner of use, it defines the nature and extent

of potential exposure. The toxicokinetic and toxicological studies

and information submitted in accordance with points 5.1 to 5.8

provide essential information as to toxicity to vertebrate species

and the mechanisms involved.

(v) Where relevant, tests should be designed and data analysed using

appropriate statistical methods. Full details of the statistical

analysis should be reported (e. g. all point estimates should be

given with confidence intervals, exact p-values should be given

rather than stating significant/non significant).

Test substance

(vi) A detailed description (specification) of the material used, as

provided for under point 1.11 must be provided. Where testing is

done using active substance the material used should be of that

specification that will be used in the manufacture of preparations

to be authorized except where radiolabelled material is used.

(vii) Where studies are conducted using active substance produced in

the laboratory or in a pilot plant production system, the studies

must be repeated using active substance as manufactured, unless

it can be justified that the test material used is essentially the

same, for the purposes of ecotoxicological testing and

assessment. In cases of uncertainty, appropriate bridging studies

must be submitted to serve as a basis for a decision as to the

possible need for repetition of the studies.

(viii) In the case of studies in which dosing extends over a period,

dosing should preferably be done using a single batch of active

substance if stability permits.

Whenever a study implies the use of different doses, the rela-

tionship between dose and adverse effect must be reported.

(ix) For all feeding studies, average achieved dose must be reported,

including where possible the dose in mg/kg body weight. Where

dosing via the diet is utilized the test compound must be

distributed uniformly in the diet.

(x) It may be necessary to conduct separate studies for metabolites,

degradation or reaction products, where these products can

constitute a relevant risk to non-target organisms and where their

effects cannot be evaluated by the available results relating to the

active substance. Before such studies are performed the

information from points 5, 6 and 7 has to be taken into account.

Test organisms

(xi) In order to facilitate the assessment of the significance of test

results obtained, including the estimation of intrinsic toxicity and

the factors affecting toxicity, the same strain (or recorded origin)

of each relevant species should, where possible, be used in the

various toxicity tests specified.

8.1.

Effects on birds

8.1.1.

Acute oral toxicity

Aim of the test

The test should provide, where possible, LD 50 values, the lethal

threshold dose, time courses of response and recovery and the

NOEL, and must include relevant gross pathological findings.

Circumstances in which required

The possible effects of the active substance on birds must be inves-

tigated except where the active substance is intended solely to be

included in preparations for exclusive use in enclosed spaces (e.g.

in glasshouses or in food storage practice).

Test conditions

The acute oral toxicity of active substance to a quail species

(Japanese quail(Coturnix coturnix japonica)or Bobwhite quail

(Colinus virginianus)or to mallard duck(Anas platyrhynchos)must be

determined. The highest dose used in tests need not exceed 2 000

mg/kg body weight.

Test guideline

Setac—Procedures for assessing the environmental fate and

ecotoxicity of pesticides ( 1 ).

( 1 ) Society of Environmental Toxicology and Chemistry (Setac), 1995.Procedures for

Assessing the Environmental Fate and Ecotoxicity of Pesticides,ISBN 90-5607-002-9.

8.1.2.

Short-term dietary toxicity

Aim of the test

The test should provide the short term dietary toxicity (LC 50 values,

lowest lethal concentration (LLC), where possible no observed effect

concentrations (NOEC), time courses of response and recovery) and

include relevant gross pathological findings.

Circumstances in which required

The dietary (five-day) toxicity of the active substance to birds must

always be investigated on one species except where a study in

accordance with the provisions of point 8.1.3 is reported. Where its

acute oral NOEL is=500 mg/kg body weight or where the short-term

NOEC < 500 mg/kg food the test must be performed on a second

species.

Test conditions

The first species to be studied must be either a quail species or

mallard duck. If a second species must be tested it should not be

related to the first species tested.

Test guideline

The test must be carried out in accordance with OECD Method 205.

8.1.3.

Subchronic toxicity and reproduction

Aim of the test

The test should provide the subchronic toxicity and reproductive

toxicity of the active substance to birds.

Circumstances in which required

The subchronic and reproductive toxicity of the active substance to

birds must be investigated, unless it can be justified that continued or

repeated exposure of adults, or exposure of nest sites during the

breeding season is unlikely to occur.

Test guideline

The test must be carried out in accordance with OECD Method 206.

8.2.

Effects on aquatic organisms

The data of the tests referred to in points 8.2.1, 8.2.4 and 8.2.6 have

to be submitted for every active substance even when it is not

expected that plant protection products containing it could reach

surface water following the proposed conditions of use. These data

are required under the provisions of Annex VI to Directive

67/548/EEC for the classification of the active substance.

Data reported must be supported with analytical data on concen-

trations of the test substance in the test media.

8.2.1.

Acute toxicity to fish

Aim of the test

The test should provide the acute toxicity (LC 50 ), and details of

observed effects.

Circumstances in which required

The test must always be carried out.

Test conditions

The acute toxicity of the active substance must be determined for

rainbow trout(Oncorhynchus mykiss)and for a warm water fish

species. Where tests with metabolites, degradation or reaction

products have to be performed the species used must be the more

sensitive of the two species tested with the active substance.

Test guideline

The test must be carried out in accordance with the Annex to

Commission Directive 92/69/EEC adapting to technical progress for

the 17th time Directive 67/548/EEC on the approximation of laws,

regulations and administrative provisions relating to the classi-

fication and labelling of dangerous, substances, Method C1.

8.2.2.

Chronic toxicity to fish

Circumstances in which required

A chronic toxicity study must be carried out unless it can be justified

that continued or repeated exposure of fish is unlikely to occur or

unless a suitable microsom or mesocosm study is available.

Expert judgment is required to decide which test has to be performed.

In particular for active substance for which there are indications of

particular concerns (related to the toxicity of the active substance for

fish or the potential exposure) the applicant shall seek the agreement

of the competent authorities on the type of test to be performed.

A fish early life stage toxicity test might be appropriate where

bioconcentration factors (BCF) are between 100 and 1 000 or where

EC 50 of the active substance < 0,1 mg/l.

A fish life cycle test might be appropriate in cases where

—the bioconcentration factor is greater tan 1 000 and the elimi-

nation of the active substance during a depuration phase of 14

days is lower than 95 %,

or

—the substance is stable in water or sediment (DT 90 > 100 days).

It is not necessary to perform a chronic toxicity test on juvenile fish

when a fish early life stage toxicity test or a fish life cycle test has

been performed; it is likewise not necessary to perform a fish early

life stage toxicity test when a fish life cycle test has been performed.

8.2.2.1.

Chronic toxicity test on juvenile fish

Aim of the test

The test should provide effects on growth, the threshold level for

lethal effects and for observed effects, the NOEC and details of

observed effects.

Test conditions

The test must be conducted on juvenile rainbow trout, following

exposure of 28 days to the active substance. Data on the effects on

growth and behaviour must be generated.

8.2.2.2.

Fish early life stage toxicity test

Aim of the test

The test should provide effects on development, growth and

behaviour, the NOEC and details of observed effects on fish early

life stages.

Test guideline

The test must be carried out in accordance with OECD Method 210.

8.2.2.3.

Fish life cycle test

Aim of the test

The test will provide effects on reproduction of the parental and the

viability of the filial generation.

Test conditions

Before performing these studies the applicant shall seek the

agreement of the competent authorities on the type and conditions of

the study to be performed.

8.2.3.

Bioconcentration in fish

Aim of the test

The test should provide the steady-state bioconcentration factors,

uptake rate constants and depuration rate constants, calculated for

each test compound, as well as relevant confidence limits.

Circumstances in which required

The bioconcentration potential of active substances, of metabolites

and of degradation and reaction products, likely to partition into fatty

tissues (such as log p ow =3—see point 2.8 or other relevant

indications of bioconcentration), must be investigated and be

reported, unless it can be justified that exposure leading to biocon-

centration is not likely to occur.

Test guideline

The test must be carried out in accordance with OECD Method 305E.

8.2.4.

Acute toxicity to aquatic invertebrates

Aim of the test

The test should provide the 24 and 48-hour acute toxicity of the

active substance, expressed as the median effective concentration

(EC 50 ) for immobilization, and where possible the highest concen-

tration causing no immobilization.

Circumstances in which required

The acute toxicity must always be determined forDaphnia

(preferablyDaphnia magna). Where plant protection products

containing the active substance are intended to be used directly on

surface water additional data have to be reported on at least one

representative species from each of the following groups: aquatic

insects, aqautic crustaceans (on a species not related toDaphnia) and

aquatic gastropod molluscs.

Test guideline

The test must be carried out in accordance with Directive 92/69/EEC,

Method C2.

8.2.5.

Chronic toxicity to aquatic invertebrates

Aim of the test

The test should provide where possible EC 50 values for effects such

as immobilization and reproduction and the highest concentration at

which no effect such as on martality or reproduction occurs (NOEC)

and details of observed effects.

Circumstances in which required

A test onDaphniaand on at least one representative aquatic insect

species and an aquatic gastropod mollusc species must be carried out

unless it can be justified that continued or repeated exposure is not

likely to occur.

Test conditions

The test withDaphniamust be continued for 21 days.

Test guideline

The test must be carried out in accordance with OECD Method 202,

Part II.

8.2.6.

Effects on algal growth

Aim of the test

The test should procide EC 50 values for growth and growth rate,

NOEC values, and details of observed effects.

Circumstances in which required

Possible effects on algal growth of active substances must always be

reported.

For herbicides a test on a second species from a different taxonomic

group has to be performed.

Test guideline

The test must be carried out in accordance with Directive 92/69/EEC,

Method C3.

8.2.7.

Effects on sediment dwelling organisms

Aim of test

The test will measure effects on survival and development (including

effects on emergence of adults forChironomus),the relevant EC 50

values and the NOEC values.

Circumstances in which required

Where environmental fate and behaviour data required in point 7

report that an active substance is likely to partition to and persist in

aquatic sediments, expert judgement should be used to decide

whether an acute or a chronic sediment toxicity test in required. Such

expert judgement should take into account whether effects on

sediment dwelling invertebrates are likely by comparing the aquatic

invertebrate toxicity EC 50 data from points 8.2.4 and 8.2.5 with the

predicted levels of the active substances in sediment from data in

Schedule III, point 9.

Test conditions

Before performing these studies the applicant shall seek the

agreement of the competent authorities on the type and conditions of

the study to be performed.

8.2.8.

Aquatic plants

A test on aquatic plants has to be performed for herbicides.

Before performing these studies the applicant shall seek the

agreement of the competent authorities on the type and conditions of

the study to be performed.

8.3.

Effect on arthropods

8.3.1.

Bees

8.3.1.1.

Acute toxicity

Aim of the test

The test should provide the acute oral and contact LD 50 value of the

active substance.

Circumstances in which required

Potential impact on bees must be investigated, except where

preparations containing the active substance are for exclusive use in

situations where bees are not likely to be exposed such as

—food storage in enclosed spaces,

—non-systemic seed dressings,

—non-systemic preparations for application to soil,

—non-systemic dipping treatments for transplanted crops and bulbs,

—wound sealing and healing treatments,

—rodenticidal baits,

—use in glasshouses without pollinators.

Test guideline

The test must be carried out in accordance with EPPO Guideline 170.

8.3.1.2.

Bee brood feeding test

Aim of the test

The test should provide sufficient information to evaluate possible

risks from the plant protection product on honeybee larvae.

Circumstances in which required

The test must be carried out when the active substance may act as an

insect growth regulator unless it can be justified that it is not likely

that bee brood would be exposed to it.

Test guideline

The test must be carried out in accordance with ICPBR Method (e.g.

P. A. Oomen, A. de Riujter and J. van der Steen. Method for

honeybee brood feeding tests with insect growth-regulating insec-

ticides.EPPO Bulletin,Volume 22, pp 613 to 616, 1992.)

8.3.2.

Other arethropods

Aim of the test

The test should provide sufficient information to evaluate the

toxicity (mortality and sublethal effects) of the active substance to

selected arthropod species.

Circumstances in which required

Effects on non-target terrestrial arthropods (e.g. predators or para-

sitoids of harmful organisms) must be investigated. The information

obtained for these species can also be used to indicate the potential

for toxicity to other non-target species inhabiting the same environ-

ment. This information is required for all active substances except

where preparations containing the active substance are for exclusive

use in situations where non-target arthropods are not exposed such

as

—food storage in enclosed spaces,

—wound sealing and healing treatments,

—rodenticidal baits.

Test conditions

The test must be performed initially in the laboratory on an artificial

substrate (i.e. glass plate or quartz sand, as appropriate) unless

adverse effects can be clearly predicted from other studies. In these

cases, more realistic substrates may be used.

Two sensitive standard species, a parasitoid and predatory mite (e.g.

Aphidius rhopalosiphiandTyphlodromus pyri)should be tested. In

addition to these, two additional species must also be tested, which

should be relevant to the intended use of the substance. Where

possible and if appropriate, they should represent the other two

major functional groups, ground dwelling predators and foliage

dwelling predators. Where effects are observed with species relevant

to the proposed use of the product, further testing may be carried out

at the extended laboratory/semi-field level. Selection of the relevant

test species should follow the proposals outlined in Setac —

Guidance document on regulatory testing procedures for pesticides

with non-target arthropods ( 1 ). Testing must be conducted at rates

equivalent to the highest rate of field application to be

recommended.

Test guideline

Where relevant, testing should be done according to appropriate

guidelines which satisfy at least the requirements for testing as

included in Setac—Guidance document on regulatory testing

procedures for pesticides with non-target arthropods.

( 1 ) From the Workshop European Standard Characteristics of beneficials Regulatory Testing

(Escort), 28 to 30 March 1994, ISBN 0-95-22535-2-6.

8.4.

Effects on earthworms

8.4.1.

Acute toxicity

Aim of the test

The test should provide the LC 50 value of the active substance to

earthworms, where possible the highest concentration causing no

mortality and the lowest concentration causing 100 % mortality, and

must include observed morphological and behavioural effects.

Circumstances in which required

Effects on earthworms must be investigated, where preparations

containing the active substance are applied to soil, or can

contaminate soil.

Test guideline

The test must be carried out in accordance with Commission

Directive 88/302/EEC adapting to technical progress for the ninth

time Council Directive 67/548/EEC on the approximation of laws,

regulations and administrative provisions relating to the classi-

fication, packaging and labelling of dangerous substances, Part C,

Toxicity for earthworms: Artificial soil test.

8.4.2.

Sublethal effects

Aim of the test

The test should provide the NOEC and the effects on growth, repro-

duction and behaviour.

Circumstances in which required

Where on the basis of the proposed manner of use of preparations

containing the active substance or on the basis of its fate and

behaviour in soil (DT 90 > 100 days), continued or repeated exposure

of earthworms to the active substance, or to significant quantities of

metabolites, degradation or reaction products, can be anticipated

expert judgement is required to decide whether a sublethal test can

be useful.

Test conditions

The test must be carried out onEisenia foetida.

8.5.

Effects on soil non-target micro-organisms

Aim of the test

The test should provide sufficient data to evaluate the impact of the

active substance on soil microbial activity, in terms of nitrogen trans-

formation and carbon mineralization.

Circumstances in which required

The test must be carried out where preparations containing the active

substance are applied to soil or can contaminate soil under practical

conditions of use. In the case of active substances intended for use in

preparations for soil sterilization, the studies must be designed to

measure rates of recovery following treatment.

Test conditions

Soils used must be freshly sampled agricultural soils. The sites from

which soil is taken must not have been treated during the previous

two years with any substance that could substantially alter the

diversity and levels of microbial populations present, other than in a

transitory manner.

Test guideline

Setac—Procedures for assessing the environmental fate and

ecotoxicity of pesticides.

8.6.

Effects on other non-target organisms (flora and fauna) believed

to be at risk

A summary of available data from preliminary tests used to assess

the biological activity and dose range finding, whether positive or

negative, which may provide information with respect to possible

impact on other non-target species, both flora and fauna, must be

provided, together with a critical assessment as to its relevance to

potential impact on non-target species.

8.7.

Effects on biological methods for sewage treatment

Effects on biological methods for sewage treatment must be reported

where the use of plant protection products containing the active

substance can give rise to adverse effects on sewage treatment

plants.

9. Summary and evaluation of points 7 and 8

10. Proposals including justification for the proposals for the classifi-

cation and labelling of the active substance according to Council

Directive 67/548/EEC

—Hazard symbol(s)

—Indications of danger

—Risk phrases

—Safety phrases

11. A dossier as referred to in Schedule III, part A, for a representative

plant protection product

PART B

Introduction

(i) Active substances are defined in regulation 2(4) and include chemical

substances and micro-organisms including viruses.

This Part provides data requirements for active substances consisting of

micro-organisms, including viruses.

For the purposes of Schedule II, Part B, the term‘micro-organism’is used

and is defined as follows:‘A microbiological entity, cellular or non-

cellular, capable of replication or of transferring genetic material’.

The definition applies to, but is not limited to, bacteria, fungi, protozoa,

viruses and viroids.

(ii) For all micro-organisms that are subject to application all available relevant

knowledge and information in literature should be provided.

The most important and informative information is obtained by the char-

acterisation and identification of a micro-organism. Such information is

found in sections 1 to 3 (identity, biological properties and further infor-

mation) which form the basis for an assessment of human health and

environmental effects.

Newly generated data from conventional toxicological and/or pathological

experiments on laboratory animals are normally required unless the

applicant can justify, on the basis of the previous information, that the use

of the micro-organism, under the proposed conditions of use, does not

have any harmful effects on human and animal health or on groundwater

or any unacceptable influence on the environment.

(iii) Pending the acceptance of specific guidelines at international level, the

information required shall be generated using available test guidelines

accepted by the director (e.g. USEPA guideline ( 1 )); where appropriate test

guidelines as described in Schedule II, Part A, should be adapted in such a

way that they are appropriate for micro-organisms. Testing should include

viable and, if appropriate, non-viable micro-organisms, and a blank

control.

(iv) Where testing is done, a detailed description (specification) of the material

used and its impurities, according to the provisions of section 1, point 1.4,

must be provided. The material used should be of that specification that

will be used in the manufacture of preparations to be authorised.

Where studies are conducted using micro-organisms produced in the

laboratory or in a pilot plant production system, the studies must be

repeated using micro-organisms as manufactured, unless it can be demon-

strated that the test material used is essentially the same for the purposes

of the testing and assessment.

(v) Where the micro-organism has been genetically modified, as defined in

Directive 2001/18/EC of the European Parliament and of the Council of

12 March 2001 on the deliberate release into the environment of

genetically modified organisms and repealing Council Directive

90/220/EEC, a copy of the evaluation of the data concerning the

assessment of risk to the environ-ment, as stated in Article 1(3) of

Directive 91/414/EEC, has to be submitted.

(vi) Where relevant, data should be analysed using appropriate statistical

methods. Full details of the statistical analysis should be reported (e.g. all

point estimates should be given with confidence intervals, exact p-values

should be given rather than stating significant/non significant).

(vii) In the case of studies in which dosing extends over a period, dosing should

preferably be done using a single batch of the micro-organism, if stability

permits.

If the studies are not performed using a single batch of the micro-

organism, the similarity of the different batches has to be stated.

Whenever a study implies the use of different doses, the relationship

between dose and adverse effect must be reported.

(viii) If the plant protection action is known to be due to the residual effect of a

toxin/metabolite or if significant residues of toxins/metabolites are to be

expected not related to the effect of the active substance, a dossier for the

toxin/metabolite has to be submitted in accordance with the requirements

of Schedule II, Part A.

( 1 )USEPA Microbial Pesticide Test Guidelines, OPPTS Series 885, February

1996(http://www.epa.gov/oppbppd1/biopesticides/guidelines/series885.htm).

1. IDENTITY OF THE MICRO-ORGANISM The identification

together with the characterisation of the micro-organism provides the

most important information and is a key point for decision-making.

1.1.

Applicant

The name and address of the applicant (permanent community

address) must be provided, as must the name, position, telephone and

fax number of the appropriate person to contact.

Where, in addition, the applicant has an office, agent or representative

in the Member State to which the application for inclusion in

Schedule I is submitted, and if different, in the rapporteur Member

State appointed by the Commission, the name and address of the local

office, agent or representative must be provided, as must the name,

position, telephone and fax number of the appropriate person to

contact.

1.2.

Producer

The name and address of the producer or producers of the micro-

organism must be provided as must the name and address of each

plant in which the micro-organism is produced. A contact point

(preferably a central contact point, to include name, telephone and fax

number) must be provided, with a view to providing updating

information and responding to queries arising, regarding production

technology, processes and the quality of product (including where

relevant, individual batches). Where, following inclusion of the

micro-organism in Schedule I, there are changes in the location or

number of producers, the information required must again be notified

to the Commission and the Member States.

1.3.

Name and species description, strain characterisation

(i) The micro-organism should be deposited at an internationally

recognised culture collection and given an accession number and

these details must be submitted.

(ii) Each micro-organism that is subject to the application should be

identified and named at the species level. The scientific name and

taxonomic grouping, i.e. family, genus, species, strain, serotype,

pathovar or any other denomination relevant to the micro-

organism, must be stated.

It must be indicated whether the micro-organism

—is indigenous or non-indigenous at the species level to the

intended area of application,

—is a wild type,

—is a spontaneous or induced mutant,

—has been modified, using techniques described in Annex IA,

Part 2, and Annex IB to Directive 2001/18/EEC.

In the latter two cases, all known differences between the

modified micro-organism and the parent wild strain must be

provided.

iii) Best available technology should be used to identify and charac-

terise the micro-organism at the strain level. The appropriate test

procedures and criteria used for identification (e.g. morphology,

biochemistry, serology, molecular identification) must be

provided.

iv) Common name or alternative and superseded names and code

names used during the development, if any, must be provided.

(v) Relationships to known pathogens should be indicated.

1.4.

Specification of the material used for manufacturing of

formulated products

1.4.1.

Content of the micro-organism

The minimum and maximum content of the micro-organism in the

material used for manufacturing of formulated products, must be

reported. The content should be expressed in appropriate terms, such

as number of active units per volume or weight or any other manner

that is relevant to the micro-organism.

Where the information provided relates to a pilot plant production

system, the information required must again be provided to the

Commission and the Member States once industrial scale production

methods and procedures have stabilised, if production changes result

in a changed specification of purity.

1.4.2.

Identity and content of impurities, additives, contaminating micro-

organisms

It is desirable to have a plant protection product without contaminants

(including contaminating micro-organisms), if possible. The level and

nature of acceptable contaminants should be judged from a risk

assessment point of view, by the director.

If possible and appropriate, the identity and maximum content of all

contaminating micro-organisms, expressed in the appropriate unit,

must be reported. The information on identity must be provided where

possible as outlined in Schedule II, Part B, section1, point 1.3.

Relevant metabolites (i.e. if expected to be of concern to human

health and/or the environment) known to be formed by the micro-

organism should be identified and characterised at different states or

growth stages of the micro-organism (see Schedule IIB, Introduction,

(viii)).

Where relevant detailed information on all components such as

condensates, culture medium, etc. must be provided.

In the case of chemical impurities that are relevant for human health

and/or the environment, the identity and maximum content, expressed

in appropriate terms, must be provided.

In the case of additives, the identity and content in g/kg must be

provided.

The information on identity of chemical substances such as additives

must be provided as outlined in Schedule II, Part A, section 1, point

1.10.

1.4.3.

Analytical profile of batches

Where relevant, the same data as outlined in Schedule II, Part A,

section 1, point 1.11, have to be reported, using the appropriate units.

2. BIOLOGICAL PROPERTIES OF THE MICRO-ORGANISM

2.1.

History of the micro-organism and its uses. Natural occurrence

and geographical distribution

Familiarity, interpreted as the availability of relevant knowledge of

the micro-organism, should be presented.

2.1.1.

Historical background

The historical background of the micro-organism and its use (tests/re-

search projects or commercial use) must be provided.

2.1.2.

Origin and natural occurrence

The geographical region and the place in the ecosystem (e.g. host

plant, host animal, or soil from which the micro-organism was

isolated) must be stated. The method of isolation of the micro-

organism should be reported. The natural occurrence of the micro-

organism in the relevant environment shall be given if possible at

strain level.

In the case of a mutant, or a genetically modified micro-organism (as

defined in Annex IA, Part 2, and Annex IB to Directive

2001/18/EEC), detailed information should be provided on its

production and isolation and on the means by which it can be clearly

distinguished from the parent wild strain.

2.2.

Information on target organism(s)

2.2.1.

Description of the target organism(s) Where relevant, details of

harmful organisms against which protection is afforded, must be

provided.

2.2.2.

Mode of action

The principal mode of action should be indicated. In connection with

the mode of action it should also be stated if the micro-organism

produces a toxin with a residual effect on the target organism. In that

case, the mode of action of this toxin should be described.

If relevant, information on the site of infection and mode of entry into

the target organism and its susceptible stages should be given. The

results of any experimental studies must be reported.

It should be stated by which way an uptake of the micro-organism, or

its metabolites (especially toxins) may occur (e.g. contact, stomach,

inhalation). It must also be stated whether or not the micro-organism

or its metabolites are translocated in plants and, where relevant, how

this translocation takes place.

In case of pathogenic effect on the target organism, infective dose (the

dose needed to cause infection with the intended effect on a target

species) and transmissibility (possibility of spread of the micro-

organism in the target population, but also from one target species to

another (target) species) after application under the proposed

condition of use shall be indicated.

2.3.

Host specificity range and effects on species other than the target

harmful organism

Any available information on the effects on non-target organisms

within the area to which the micro-organism may spread shall be

given. The occurrence of non-target organisms being either closely

related to the target species or being especially exposed shall be

indicated.

Any experience of the toxic effect of the active substance or its

metabolic products on humans or animals, of whether the organism is

capable of colonising or invading humans or animals (including

immunosuppressed individuals) and whether it is pathogenic shall be

stated. Any experience of whether the active substance or its products

may irritate skin, eyes or respiratory organs of humans or animals and

whether it is allergenic in contact with skin or when inhaled shall be

stated.

2.4.

Development stages/life cycle of the micro-organism

Information on the life cycle of the micro-organism, described

symbiosis, parasitism, competitors, predators, etc., including host

organisms, as well as vectors for viruses, must be presented.

The generation time and the type of reproduction of the micro-

organism must be stated.

Information on the occurrence of resting stages and their survival

time, their virulence and infection potential must be provided.

The potential of the micro-organism to produce metabolites, including

toxins that are of concern for human health and/or the environment, in

its different development stages after the release, must be indicated.

2.5.

Infectiveness, dispersal and colonisation ability

The persistence of the micro-organism and information on its life

cycle under the typical environmental conditions of use must be

indicated. In addition, any particular sensitivity of the micro-organism

to certain compartments of the environment (e.g. UV light, soil,

water) must be stated.

The environmental requirements (temperature, pH, humidity, nutrition

requirements, etc.) for survival, reproduction, colonisation, damage

(including human tissues) and effectiveness of the micro-organism

must be stated. The presence of specific virulence factors should be

indicated.

The temperature range at which the micro-organism grows must be

determined, including minimum, maximum and optimum

temperatures. This information is of particular value as a trigger for

studies of effects on human health (section 5).

The possible effect of factors such as temperature, UV light, pH, and

the presence of certain substances on the stability of relevant toxins

must also be stated.

Information on possible dispersal routes of the micro-organism (via

air as dust particles or aerosols, with host organisms as vectors, etc.),

under typical environmental conditions relevant to the use, must be

provided.

2.6.

Relationships to known plant or animal or human pathogens The

possible existence of one or more species of the genus of the active

and/or, where relevant, contaminating micro-organisms known to be

pathogenic to humans, animals, crops or other non-target species and

the type of disease caused by them shall be indicated. It shall be stated

whether it is possible, and if so, by which means to clearly distinguish

the active micro-organism from the pathogenic species.

2.7.

Genetic stability and factors affecting it

Where appropriate, information on genetic stability (e.g. mutation rate

of traits related to the mode of action or uptake of exogenous genetic

material) under the environmental conditions of proposed use must be

provided.

Information must also be provided on the micro-organism's capacity

to transfer genetic material to other organisms as well as its capacity

to being pathogenic for plants, animals or man. If the micro-organism

carries relevant additional genetic elements, the stability of the

encoded traits should be indicated.

2.8.

Information on the production of metabolites (especially toxins)

If other strains belonging to the same microbial species as the strain

subject to the application are known to produce metabolites

(especially toxins) with unacceptable effects on human health and/or

the environ-ment during or after application, the nature and structure

of this substance, its presence inside or outside the cell and its

stability, its mode of action (including external and internal factors of

the micro-organism necessary to action) as well as its effect on

humans, animals or other non-target species shall be provided.

The conditions under which the micro-organism produces the meta-

bolite(s) (especially toxin(s)) must be described.

Any available information on the mechanism by which the micro-

organisms regulate the production of the(se) metabolite(s) should be

provided.

Any available information on the influence of the produced meta-

bolites on the micro-organism's mode of action should be provided.

2.9.

Antibiotics and other anti-microbial agents

Many micro-organisms produce some antibiotic substances. Inter-

ference with the use of antibiotics in human or veterinary medicine

must be avoided at any stage of the development of a microbial plant

protection product.

Information on the micro-organism's resistance or sensitivity to anti-

biotics or other anti-microbial agents must be provided, in particular

the stability of the genes coding for antibiotic resistance, unless it can

be justified that the micro-organism has no harmful effects on human

or animal health, or that it can not transfer its resistance to antibiotics

or other anti-microbial agents.

3. FURTHER INFORMATION ON THE MICRO-ORGANISM

Introduction

i) The information provided must describe the intended purposes for

which preparations containing the micro-organism are used, or are

to be used and the dose and manner of their use or proposed use.

(ii) The information provided must specify the normal methods and

precautions to be followed in the handling, storage and transport

of the micro-organism.

(iii) The studies, data and information submitted, must demonstrate the

suitability of measures proposed for use in emergency situations.

(iv) The information and data referred to are required for each micro-

organism, except where otherwise specified.

3.1.

Function

The biological function must be specified from among the following

—control of bacteria,

—control of fungi,

—control of insects,

—control of mites,

—control of molluscs,

—control of nematodes,

—control of weeds,

—other (must be specified).

3.2.

Field of use envisaged

The field(s) of use, existing and proposed, for preparations containing

the micro-organism must be specified from among the following

—field use, such as agriculture, horticulture, forestry, and viticulture,

—protected crops (e.g. in greenhouses),

—amenity,

—weed control on non-cultivated areas,

—home gardening,

—house plants,

—stored products,

—other (specify).

3.3.

Crops or products protected or treated Details of existing and

intended use in terms of crops, groups of crops, plants, or plant

products protected, must be provided.

3.4.

Method of production and quality control

Full information on how the micro-organism is produced in bulk must

be provided.

Both production method/process and product must be subject to a

continuous quality control by the applicant. In particular, the

occurrence of spontaneous changing of major characteristics of the

micro-organism and of the absence/presence of significant

contaminants should be monitored. The quality assurance criteria for

the production should be submitted.

The techniques used to ensure a uniform product, and the assay

methods for its standardisation, maintenance and purity of the micro-

organism must be described and specified (e.g. HACCP).

3.5.

Information on the occurrence or possible occurrence of the devel-

opment of resistance of the target organism(s)

Available information on the possible occurrence of the development

of resistance or cross-resistance of the target organism(s) must be

provided. Where possible, appropriate management strategies should

be described.

3.6.

Methods to prevent loss of virulence of seed stock of the micro-

organism

Methods to prevent loss of virulence of starting cultures are to be

provided.

In addition, any method, if available, that could prevent the micro-

organism from losing its effects on the target species must be

described.

3.7.

Recommended methods and precautions concerning handling,

storage, transport or fire

A safety data sheet similar to that required for chemical active

substances in Article 27 of Directive 67/548/EEC ( 1 ) must be

provided for each micro-organism.

3.8.

Procedures for destruction or decontamination

In many cases the preferred or sole means of safe disposal of micro-

organisms, contaminated materials, or contaminated packaging, is

through controlled incineration in a licensed incinerator.

Methods to dispose safely of the micro-organism or, where necessary,

to kill it prior to disposal, and methods to dispose of contaminated

packaging and contaminated materials, must be fully described. Data

must be provided for such methods to establish their effectiveness and

safety.

( 1 ) See doc. 6853/VI/98, Concise outline report of the first peer review meeting on micro-

organisms.

3.9.

Measures in case of an accident Information on procedures for

rendering the micro-organism harmless in the environment (e.g. water

or soil) in case of an accident must be provided.

4. ANALYTICAL METHODS

Introduction

The provisions of this section only cover analytical methods required

for post-registration control and monitoring purposes.

Post-approval monitoring might be considered for all areas of risk

assessment. This is particularly the case when (strains of) micro-

organisms that are non-indigenous to the intended area of application

are considered for approval. For analytical methods used for

generation of data as required in this Directive or for other purposes

the applicant has to provide a justification for the method used; where

necessary separate guidance will be developed for such methods on

the basis of the same requirements as defined for methods for post-

regis-tration control and monitoring purposes.

Descriptions of methods must be provided and include details of

equipment, materials and conditions used. The applicability of any

internationally recognised method must be reported.

As far as practicable these methods must employ the simplest

approach, involve the minimum cost, and require commonly available

equipment.

Data on specifity, linearity, accuracy and repeatability, as defined in

Schedule II, Part A, points 4.1 and 4.2, are also required for methods

used to analyse micro-organisms and their residues.

For this section the following applies

Impurities

Any component (including contami-

nating

micro-organisms

and/or

chemical substances) other than the

specified micro-organism, originating

from the manufacturing process or from

degradation during storage

Relevant impurities

Impurities, as defined above, that are of

concern for human or animal health

and/or the environment

Metabolites

Metabolites include products resulting

from degradative and biosynthetic

reactions taking place within the micro-

organism or other organisms used to

produce the micro-organism of interest

Relevant metabolites

Metabolites that are of concern for

human or animal health and/or the en-

vironment

Residues

Viable micro-organisms and substances

produced in significant quantities by

these micro-organisms which persist

after the disappearance of the micro-

organisms and are of concern for human

or animal health and/or the envi-ronment.

On request the following samples must be provided

(i) samples of the micro-organism as manufactured;

(ii) analytical standards of relevant metabolites (especially toxins) and

all other components included in the residue definition;

(iii) if available, samples of reference substances for the relevant impu-

rities.

4.1.

Methods for the analysis of the micro-organism as manufactured

—Methods for the identification of the micro-organism.

—Methods for providing information on possible variability of seed

stock/active micro-organism.

—Methods to differentiate a mutant of the micro-organism from the

parent wild strain.

—Methods for the establishment of purity of seed stock from which

batches are produced and methods to control that purity.

—Methods to determine the content of the micro-organism in the

manufactured material used for the production of formulated

products and methods to show that contaminating micro-

organisms are controlled to an acceptable level.

—Methods for the determination of relevant impurities in the manu-

factured material.

—Methods to control the absence and to quantify (with appropriate

limits of determination) the possible presence of any human and

mammalian pathogens.

—Methods to determine storage stability, shelf-life of the micro-

organism, if appropriate.

4.2.

Methods to determine and quantify residues (viable or non-viable)

of

—the active micro-organism(s),

—relevant metabolites (especially toxins), on and/or in crop, in

foodstuffs and feeding stuffs, in animal and human body tissues and

fluids, in soil, in water (including drinking water, ground water and

surface water) and in air where relevant.

Analytical methods for amount or activity of proteinaceous products

should also be included, e.g. by testing exponential cultures and

culture supernatants in an animal cell bioassay.

5. EFFECTS ON HUMAN HEALTH

Introduction

(i) Available information based on the properties of the micro-

organism and corresponding organisms (sections 1 to 3), including

health and medical reports may be sufficient for a decision

whether the micro-organism would cause health effects

(infectious/pathogenic/toxic) in humans or not.

(ii) The information provided, taken together with that provided for

one or more preparations containing the micro-organism, must be

sufficient to permit an evaluation to be made as to the risks for

man, directly and/or indirectly associated with the handling and

use of plant protection products containing the micro-organism,

and the risk for man handling treated products, and the risk for

man arising from residual traces or contaminants remaining in

food and water.

In addition, the information provided must be sufficient to

—permit a decision to be made as to whether, or not, the micro-

organism can be included in Schedule I,

—specify appropriate conditions or restrictions to be associated

with any inclusion in Schedule I,

—specify risk and safety phrases (once introduced) for the

protection of man, animals and the environment to be included

on packaging (containers),

—identify relevant first aid measures as well as appropriate diag-

nostic and therapeutic measures to be followed in the event of

infection or another adverse effect in man.

(iii) All effects found during investigations should be reported. Inves-

tigations which may be necessary in order to evaluate the probable

mechanism involved, and to assess the significance of these

effects, must also be performed.

(iv) For all studies actual achieved dose in colony forming units per kg

body weight (cfu/kg), as well as in other appropriate units, must be

reported.

(v) Evaluation of the micro-organism should be carried out in a tier-

wise manner.

The first tier (Tier I) includes available basic information and basic

studies, which have to be performed for all micro-organisms.

Expert judgment will be necessary to decide about the appropriate

test programme on a case-by-case basis. Newly generated data

from conventional toxicological and/or pathological experiments

on laboratory animals are normally required unless the applicant

can justify, on the basis of the previous information, that the use of

the micro-organism, under the proposed conditions of use, does

not have any harmful effects on human and animal health. Pending

the acceptance of specific guidelines at international level, the

infor-mation required shall be generated using available test

guidelines (e.g. USEPA OPPTS Guidelines).

Tier II studies must be conducted if tests under Tier I have shown

adverse health effects. The type of study to be performed depends

on the effects observed in the Tier I studies. Before performing

such studies, the applicant shall seek agreement of the competent

authorities on the type of study to be performed.

TIER I

5.1.

Basic information

Basic information is required about the micro-organism's potential to

cause adverse effects such as ability to colonise, to cause damage and

to produce toxins and other relevant metabolites.

5.1.1.

Medical data

Where available, and without prejudice to the provisions of Article 5

of Council Directive 98/24/EC of 7 April 1998 on the protection of

the health and safety of workers from the risks related to chemical

agents at work and Directive 2000/54/EC of the European Parliament

and of the Council of 18 September 2000 on the protection of workers

from risks related to exposure to biological agents at work, practical

data and information relevant to the recognition of the symptoms of

infection or pathogenicity and on the effectiveness of first aid and

therapeutic measures have to be submitted. Where relevant, the

effectiveness of potential antagonists, should be inves-tigated and

reported. Where relevant, methods to kill or render the micro-

organism uninfective must be indicated (see section 3, point 3.8).

Data and information relevant to the effects of human exposure,

where available and of the necessary quality, are of particular value,

in confirming the validity of extrapolations made and conclusions

reached with respect to target organs, virulence, and the reversibility

of adverse effects. Such data can be generated following accidental or

occupational exposure.

5.1.2.

Medical surveillance on manufacturing plant personnel

Available reports of occupational health surveillance programmes,

supported with detailed information on the design of the programme

and on exposure to the micro-organism must be submitted. Such

reports should, where feasible, include data relevant to the mechanism

of action of the micro-organism. These reports shall, where available,

include data from persons exposed in manufacturing plants or after

application of the micro-organism (e.g. in efficacy trials).

Special attention should be devoted to those whose susceptibility may

be affected, e.g. pre-existing disease, medication, compromised

immunity, pregnancy or breast feeding.

5.1.3.

Sensitisation/allergenicity observations, if appropriate

Available information on the sensitisation and allergenic response of

workers, including workers in manufacturing plants, agricultural and

research workers and others exposed to the micro-organism must be

provided, and include, where relevant, details of any incidences of

hypersensitivity and chronic sensitisation. The information provided

should include details of frequency, level and duration of exposure,

symptoms observed and other relevant clinical observation. Infor-

mation should be given about whether workers have been subjected to

any allergy tests or interviewed about allergenic symptoms.

5.1.4.

Direct observation, e.g. clinical cases

Available reports from the open literature on the micro-organism or

closely related members of the taxonomic group (relating to clinical

cases), where they are from reference journals or official reports, must

be submitted together with reports of any follow-up studies

undertaken. Such reports are of particular value and should contain

complete descriptions of the nature, level and duration of exposure, as

well as the clinical symptoms observed, first aid and therapeutic

measures applied and measurements and observations made.

Summary and abstract information is of limited value.

If there are animal studies performed, reports relating to clinical cases

can be of particular value in confirming the validity of interpretations

from animal data to man and in identifying unexpected adverse effects

which are specific to humans.

5.2.

Basic studies

In order to make it possible to correctly interpret the obtained results,

it is of greatest importance that the suggested test methods are

relevant regarding species sensitivity, administration route, etc., and

relevant from a biological and toxicological point of view. The way of

admin-istration of the test micro-organism depends on the main

exposure routes to humans.

To evaluate medium- and long-term effects after acute, sub-acute or

semi-chronic exposure to micro-organisms, it is necessary to use the

options provided in most of the OECD guidelines, to extend the

studies concerned with a recovery period (after which full

macroscopic and microscopic pathology is to be performed, including

an exploration for micro-organisms in the tissues and organs). This

facil-itates the interpretation of certain effects and provides the

possibility to recognise infectiveness and/or pathogenicity, which in

turn helps taking decisions on other issues such as the necessity to

perform long-term studies (carcinogenicity etc., see point 5.3), and

whether or not to perform residue studies (see point 6.2).

Sensitisation( 1 )

5.2.1.

Aim of the test

The test will provide sufficient information to assess the potential of

the micro-organism to provoke sensitisation reactions by inhalation as

well as with dermal exposure. A maximised test has to be performed.

Circumstances in which required( 2 )

Information on sensitisation must be reported.

5.2.2.

Acute toxicity, pathogenicity and infectiveness

The studies, data and information to be provided and evaluated must

be sufficient to permit the identification of effects following a single

exposure to the micro-organism, and in particular to establish, or

indicate

—the toxicity, pathogenicity and infectiveness of the micro-organism,

—the time course and characteristics of the effects with full details of

behavioural changes and possible gross pathological findings at

post-mortem,

—where possible mode of toxic action,

—the relative hazards associated with the different routes of exposure,

and

—blood analyses throughout the studies in order to evaluate the

clearance of the micro-organism.

Acute toxic/pathogenic effects may be accompanied by infectiveness

and/or more long-term effects which cannot be observed immediately.

With a view to health evaluation, it is therefore necessary to carry out

studies on the ability to infect in connection with oral intake, inha-

lation and intraperitoneal/subcutaneous injection by test mammals.

During the acute toxicity, pathogenicity and infectiveness studies, an

estimation of the micro-organism and/or the active toxin clearance in

the organs deemed to be relevant for microbial examination (e.g.

liver, kidneys, spleen, lungs, brain, blood and site of administration)

must be performed.

The observations to be made should reflect expert scientific

judgement and may include the micro-organism numeration in all the

tissues likely to be affected (e.g. showing lesions) and in the main

organs: kidneys, brain, liver, lungs, spleen, bladder, blood, lymphatic

ganglia, gastrointestinal tract, thymus gland and lesions at the

inoculation site in the dead or moribund animals and at interim and

final sacrifice.

The information generated through acute toxicity, pathogenicity and

infectiveness testing is of particular value in assessing hazards likely

to arise in accident situations and consumer risks due to exposure to

possible residues.

( 1 ) The available methods for testing dermal sensitisation are not suitable for testing micro-

organisms. Sensitisation by inhalation is most probably a greater problem compared with dermal

exposure to micro-organisms but so far, there are no validated test methods. Development of these

kinds of methods is therefore of great importance. Until then, all micro-organisms should be

regarded as potential sensitisers. This approach also takes into consideration immuno-compromised

or other sensitive individuals in the population (e.g. pregnant women, new-born children or

elderly).

( ) As a consequence of the absence of proper test methods all micro-organisms will be

labelled as potential sensitisers, unless the applicant wants to demonstrate the non-sensi-tising

potential by submitting data. Therefore, this data requirement should be regarded as not obligatory

but optional, on a provisional base.

5.2.2.1. A c u t e o r a l t o x i c i t y , p a thogenicity and infec-

tiveness

Circumstances in which required

The acute oral toxicity, pathogenicity and infectiveness of the micro-

organism must be reported.

5.2.2.2. A c u t e i n h a l a t i o n t o x i c i t y , p a t h o g e n i c i t y a n d

infectiveness

Circumstances in which required

The inhalation toxicity ( 1 ), pathogenicity and infectiveness of the

micro-organism must be reported.

( 1 ) An inhalation study may be replaced by an intratracheal study.

5.2.2.3. I n t r a p e r i t o n e a l / s u b c u t a n e o u s s i n g l e d o s e

The intraperitoneal/subcutaneous test is considered a highly sensitive

assay to elicit in particular infectiveness.

Circumstances in which required

The intraperitoneal injection is always required for all micro-

organisms, however, expert judgement may be exercised to evaluate

whether subcutaneous injection is preferred instead of intraperitoneal

injection if the maximum temperature for growth and multiplication is

lower than 37 o C.

5.2.3.

Genotoxicity testing

Circumstances in which required

If the micro-organism produces exotoxins according to point 2.8, then

these toxins and any other relevant metabolites in the culture medium

must also be tested for genotoxicity. Such tests on toxins and meta-

bolites should be performed using the purified chemical if possible.

If basic studies do not indicate that toxic metabolites are formed,

studies on the micro-organism itself should be considered depending

on expert judgement on the relevance and validity of the basic data. In

the case of a virus the risk of insertional mutagenesis in mammal cells

or the risk of carcinogenicity has to be discussed.

Aim of the test

These studies are of value in

—the prediction of genotoxic potential,

—the early identification of genotoxic carcinogens,

—the elucidation of the mechanism of action of some carcinogens.

It is important that a flexible approach is adopted, with selection of

further tests being dependent upon interpretation of results at each

stage.

Test conditions( 1 )

Genotoxicity of cellular micro-organisms will be studied after breaking

of the cells, wherever possible. Justification should be provided on the

method of sample preparation used.

Genotoxicity of viruses should be studied on infectious isolates.

( ) As the present test methods are designed to be performed on soluble chemicals, it is

necessary that the methods are developed so as to become relevant for micro-organisms.

5.2.3.1.In vitrostudies

Circumstances in which required

Results ofin vitromutagenicity tests (bacterial assay for gene mutation,

test for clastogenicity in mammalian cells and test for gene mutation in

mammalian cells) must be provided.

5.2.4.

Cell culture study

This information must be reported for intracellular replicating micro-

organisms, such as viruses, viroids or specific bacteria and protozoa,

unless the information from sections 1 to 3 clearly demonstrates that

the micro-organism does not replicate in warm-blooded organisms. A

cell culture study should be performed in human cell or tissue cultures

of different organs. Selection can be based on expected target organs

after infection. If human cell or tissue cultures of specific organs are

not available, other mammal cell and tissue cultures can be used. For

viruses, the ability to interact with the human genome is a key consid-

eration.

5.2.5.

Information on short-term toxicity and pathogenicity

Aim of the test

Short-term toxicity studies must be designed to provide information as

to the amount of the micro-organism that can be tolerated without

toxic effects under the conditions of the study. Such studies provide

useful data on the risks for those handling and using preparations

containing the micro-organism. In particular, short-term studies

provide an essential insight into possible cumulative actions of the

micro-organism, and the risks to workers who may be intensively

exposed. In addition short-term studies provide information useful in

the design of chronic toxicity studies.

The studies, data and information to be provided and evaluated, must

be sufficient to permit the identification of effects following repeated

exposure to the micro-organism, and in particular to further establish,

or indicate

—the relationship between dose and adverse effects,

—toxicity of the micro-organism including where necessary the

NOAEL for toxins,

—target organs, where relevant,

—the time course and characteristics of the effects with full details of

behavioural changes and possible gross pathological findings at

post-mortem,

—specific toxic effects and pathological changes produced,

—where relevant the persistence and reversibility of certain toxic

effects observed, following discontinuation of dosing,

—where possible, the mode of toxic action, and

—the relative hazard associated with the different routes of exposure.

During the short-term toxicity study, an estimation of the micro-

organism clearance in the main organs must be performed.

Investigations should be included for pathogenicity and infectiveness

end points.

Circumstances in which required

The short-term toxicity (minimum 28 days) of the micro-organism

must be reported.

The choice of test species has to be justified. The choice of study

length depends on acute toxicity and clearance data.

Expert judgement is required to decide what route of administration is

preferable.

5.2.5.1. H e a l t h e f f e c t s a f t e r r e p e a t e d i n h a l a t o r y e x p o s u r e

Information on the health effects after repeated inhalatory exposure is

considered necessary, particularly for the risk assessment of the occu-

pational setting. Repeated exposure might influence the clearance

capacity (e.g. resistance) of the host (human). Furthermore, for proper

risk assessment the toxicity after repeated exposure to contaminants,

growth medium, co-formulants and the micro-organism needs to be

addressed. It should be kept in mind that the formulants in the plant

protection product can influence the toxicity and infectiveness of a

micro-organism.

Circumstances in which required

Information on the short-term infectiveness, pathogenicity and toxicity

(respiratory route) of a micro-organism is required, unless the infor-

mation already provided is sufficient to assess human health effects.

This can be the case if it is demonstrated that the test material has no

inhalable fraction and/or repeated exposure is not expected.

5.2.6.

Proposed treatment: first aid measures, medical treatment

The first aid measures to be used in the event of infection and in the

event of contamination of eyes must be provided.

Therapeutic regimes for use in the event of ingestion or contamination

of eyes and skin must be described in full. Information based on

practical experience, where it exists and is available, in other cases on

theoretical grounds, as to the effectiveness of alternative treatment

regimes, where relevant, must be provided.

Information on resistance to antibiotics must be provided.

(END OF TIER I)

TIER II

5.3.

Specific toxicity, pathogenicity and infectiveness studies

In certain cases, it can be necessary to carry out supplementary studies

to further clarify the adverse human effects.

In particular, if results from earlier studies indicate that the micro-

organism may cause long-term health effects, studies on chronic

toxicity, pathogenicity and infectiveness, carcinogenicity and repro-

ductive toxicity must be carried out. Furthermore, where a toxin is

produced, kinetic studies must be performed.

Studies required must be designed on an individual basis, in the light

of the particular parameters to be investigated and the objectives to be

achieved. Before performing such studies, the applicant shall seek

agreement of the competent authorities on the type of study to be

performed.

5.4.

In vivostudies in somatic cells

Circumstances in which required

If all the results of thein vitrostudies are negative further testing must

be done with consideration of other relevant information available. The

test can be anin vivostudy or anin vitrostudy using a different

metabolising system from that/those previously used.

If thein vitrocytogenetic test is positive, anin vivotest using somatic

cells (metaphase analysis in rodent bone marrow or micronucleus test

in rodents) must be conducted.

If either of thein vitrogene mutation tests are positive, anin vivotest to

investigate unscheduled DNA synthesis or a mouse spot test must be

conducted.

5.5.

Genotoxicity—In vivostudies in germ cells

Aim of the test and test conditions

See point 5.4.

Circumstances in which required

When any result of anin vivostudy in somatic cells is positive,in vitro

testing for germ cell effects may be justified. The necessity for

conducting these tests will have to be considered on a case-by-case

basis, taking into account other relevant information available

including use and expected exposure. Suitable tests would need to

examine inter-action with DNA (such as the dominant lethal assay), to

look at the potential for inherited effects and possibly make a

quantitative assessment of heritable effects. It is recognised that in

view of their complexity, the use of quantitative studies would require

strong justi-fication.

(END OF TIER II)

5.6.

Summary of mammalian toxicity, pathogenicity and infectiveness

and overall evaluation

A summary of all data and information provided under points 5.1

through 5.5, must be submitted, and include a detailed and critical

assessment of those data in the context of relevant evaluative and

decision making criteria and guidelines, with particular reference to the

risks for man and animals that may or do arise, and the extent, quality

and reliability of the data base.

It must be explained whether exposure of animals or humans has any

implications for vaccination or serological monitoring.

6. RESIDUES IN OR ON TREATED PRODUCTS, FOOD AND FEED

Introduction

(i) The information provided, taken together with that for one or more

preparations containing the micro-organism, must be sufficient to

permit an evaluation to be made as to the risk for man and/or

animals, arising from exposure to the micro-organism and its

residual traces and metabolites (toxins) remaining in or on plants or

plant products.

(ii) In addition, the information provided must be sufficient to

—permit a decision to be made as to whether or not the micro-

organism can be included in Annex I to Directive 91/414/EEC,

—specify appropriate conditions or restrictions to be associated

with any inclusion in Annex I to Directive 91/414/EEC,

—where relevant, set maximum residue levels, preharvest intervals

to protect consumers and waiting periods, to protect workers

handling the treated crops and products.

(iii) For the evaluation of risk arising from residues, experimental data

on levels of exposure to the residue may not be required where it

can be justified, that the micro-organism and its metabolites are not

hazardous to humans in the concentrations that could occur as a

result of authorised use. This justification can be based on open

literature, on practical experience and on information submitted in

sections 1 through 3 and section 5.

6.1.

Persistance and likelihood of multiplication in or on crops, feeding-

stuffs or foodstuffs

A substantiated estimation of persistance/competitiveness of the

micro-organism and relevant secondary metabolites (especially

toxins) in or on the crop under the environmental conditions

prevailing at and after the intended use, taking into account in

particular the information provided in section 2, has to be delivered.

Moreover, the application shall state to which extent and on which

basis it is considered that the micro-organism can (or cannot) multiply

in or on the plant or plant product or during processing of raw

products.

6.2.

Further information required Consumers may be exposed to micro-

organisms for a considerable time as a result of the consumption of

treated food commodities; potential effects on the consumers must,

therefore, be derived from chronic or semi-chronic studies, so that a

toxicological end point, such as the ADI, can be established for risk

management.

6.2.1.

Non-viable residues

A non viable micro-organism is a micro-organism that is not capable

of replication or of transferring genetic material.

If relevant quantities of the micro-organism or of produced meta-

bolites, especially toxins, have been found to be persistant in section

2, points 2.4 and 2.5, full experimental residue data as provided for in

Schedule II, Part A, section 6, is required, if concentrations of the

micro-organism and/or its toxins in or on the treated foodstuffs or

feeding-stuffs are expected to occur in concentrations higher than

under natural conditions or in a different phenotypic state.

In agreement with Directive 91/414/EEC, the conclusion concerning

the difference between natural concentrations and an elevated concen-

tration due to treatment with the micro-organism, is to be based on

experimentally obtained data, and not on extrapolations or

calculations using models.

Before performing such studies, the applicant shall seek agreement of

the competent authorities on the type of study to be performed.

6.2.2.

Viable residues

If the information submitted according to point 6.1 suggests

persistance of relevant amounts of the micro-organism in or on treated

products, food or feed, possible effects on humans and/or animals

must be investigated, unless it can be justified from section 5, that the

micro-organism and its metabolites and/or degradation products are

not hazardous to humans in the concentrations and of the nature that

could occur as a result of authorised use.

In agreement with Directive 91/414/EEC, the conclusion concerning

the difference between natural concentrations and an elevated concen-

tration due to treatment with the micro-organism, is to be based on

experimentally obtained data, and not on extrapolations or

calculations using models.

The persistence of viable residues needs special attention if infec-

tiveness or pathogenicity to mammals have been found in sections

2.3, 2.5 or 5 and/or if any other information suggests a hazard to

consumers and/or workers. In this case the competent authorities may

require studies similar to those provided for in Part A.

Before performing such studies, the applicant shall seek agreement of

the competent authorities on the type of study to be performed.

6.3.

Summary and evaluation of residue behaviour resulting from

data submitted under points 6.1 and 6.2

7. FATE AND BEHAVIOUR IN THE ENVIRONMENT

Introduction

(i) Information on the origin, the properties, and the survival of the

micro-organism and its residual metabolites as well as its intended

use form the basis for an assessment of environmental fate and

behaviour.

Experimental data are normally required unless it can be justified

that an assessment of its fate and behaviour in the environment can

be performed with the information already available. This justifi-

cation can be based on open literature, on practical experience and,

on information submitted in sections 1 through 6. The function of

the micro-organism in environmental processes (as defined in

section 2, point 2.1.2) is of particular interest.

(ii) The information provided, taken together with other relevant infor-

mation, and that for one or more preparations containing the micro-

organism, must be sufficient to permit an assessment of its fate and

behaviour as well as that of its residual traces and toxins, where

they are of significance for human health and/or the environment.

(iii) In particular, the information provided should be sufficient to

—decide whether, or not, the micro-organism can be included in

Schedule I,

—specify appropriate conditions or restrictions to be associated

with any inclusion in Schedule I,

—specify the hazard symbols (once introduced), the indications of

danger, and relevant risk and safety phrases for the protection

of the environment, which are to be included on packaging

(containers),

—predict the distribution, fate, and behaviour in the environment

of the micro-organism and its metabolites as well as the time

courses involved,

—identify measures necessary to minimise contamination of the

environment and impact on non-target species.

(iv) Any relevant metabolites (i.e. of concern for human health and/or

the environment) formed by the test organism under any relevant

environmental conditions should be characterised. If relevant meta-

bolites are present in or produced by the micro-organism, data as

outlined under Schedule II, Part A, point 7 may be required, if all

of the following conditions are met

—the relevant metabolite is stable outside the micro-organism, see

point 2.8, and

—a toxic effect of the relevant metabolite is independent of the

presence of the micro-organism, and

—the relevant metabolite is expected to occur in the environment

in concentrations considerably higher than under natural

conditions.

(v) Available information on the relationship with naturally occurring

wild type relatives should be taken into account.

(vi) Before performing studies as referred to below, the applicant shall

seek agreement of the competent authorities on whether studies

need to be performed and, if so, the type of study to be conducted.

The information from the other sections has, also, to be taken into

account.

7.1.

Persistence and multiplication

Where relevant, appropriate information on the persistence and multi-

plication of the micro-organism, in all environmental compartments

has to be given, unless it can be justified that exposure of the

particular environmental compartment to the micro-organism is

unlikely to occur. Special attention shall be given to

—competitiveness under the environmental conditions prevailing at

and after the intended use, and

—population dynamics in seasonally or regionally extreme climates

(particularly hot summer, cold winter and rainfall) and to agri-

cultural practices applied after intended use.

Estimated levels of the specified micro-organism in a time course

after use of the product under the proposed conditions of use shall be

given.

7.1.1.

Soil

Information on viability/population dynamics should be reported in

several cultivated and uncultivated soils representative of soils typical

of the various Community regions where use exists or is anticipated.

The provisions on choice of soil and its collection and handling, as

referred to in Part A, point 7.1, Introduction, have to be followed. If

the test organism is to be used in association with other media, e.g.

rockwool, this must be included in the test range.

7.1.2.

Water

Information should be reported on viability/population dynamics in

natural sediment/water systems under both dark and illuminated

conditions.

7.1.3.

Air

In case of particular concerns for operator, worker or bystander

exposure, information on the concentrations in air might be necessary.

7.2.

Mobility

The possible spread of the micro-organism and its degradation

products in relevant environmental compartments has to be evaluated,

unless it can be justified that exposure of the particular environmental

compartments to the micro-organism is unlikely to occur. In this

context, the intended use (e.g. field or greenhouse, application to soil

or to crops), life cycle stages, including occurrence of vectors,

persistence and the ability of the organism to colonise adjacent

habitats are of particular interest.

The spread, the persistence and probable transport ranges need special

attention if toxicity, infectiveness or pathogenicity have been reported

or if any other information suggests possible hazard to humans,

animals or to the environment. In this case the competent authorities

may require studies similar to those provided for in Part A. Before

performing such studies, the applicant shall seek agreement of the

competent authorities on the type of study to be performed.

8. EFFECTS ON NON-TARGET ORGANISMS

Introduction

(i) The information on identity, biological properties and further infor-

mation in sections 1 to 3 and 7 is central to the assessment of

impact on non-target species. Additional useful information may

be found on fate and behaviour in the environment in section 7 and

on residue levels in plants in section 6 which, together with infor-

mation on the nature of the preparation and its manner of use,

defines the nature and extent of potential exposure. The infor-

mation submitted in accordance with section 5 will provide

essential information as to effects to mammals and the

mechanisms involved.

Experimental data are normally required, unless it can be justified

that an assessment of effects on non-target organisms can be

performed with the information already available.

(ii) The choice of the appropriate non-target organisms for testing of

environmental effects should be based on the identity of the micro-

organism (including the host specificity, mode of action and

ecology of the organism). From such knowledge it would be

possible to choose the appropriate test-organisms, such as

organisms closely related to the target organism.

(iii) The information provided, taken together with that for one or more

preparations containing the micro-organism, must be sufficient to

permit an assessment of the impact on non-target species (flora

and fauna), likely to be at risk from exposure to the micro-

organism, where they are of environmental significance. Impact

can result from single, prolonged or repeated exposure and can be

reversible or irreversible.

(iv) In particular, the information provided for the micro-organism,

together with other relevant information, and that provided for one

or more preparations containing it, should be sufficient to

—decide whether, or not, the micro-organism can be included in

Schedule I,

—specify appropriate conditions or restrictions to be associated

with any inclusion in Schedule I,

—permit an evaluation of short- and long-term risks for non-

target species—populations, communities, and processes— as

appropriate,

—classify the micro-organism as to biological hazard,

—specify the precautions necessary for the protection of non-

target species, and

—specify the hazard symbols (once introduced), the indications of

danger, and relevant risk and safety phrases for the protection

of the environment, to be mentioned on packaging (containers).

(v) There is a need to report all potentially adverse effects found

during routine investigations on environmental effects, to

undertake and report, where required by the competent authorities,

such additional studies which may be necessary to investigate the

probable mechanisms involved and to assess the significance of

these effects. All available biological data and information which

is relevant to the assessment of the ecology profile of the micro-

organism must be reported.

(vi) For all studies, average achieved dose in cfu/kg body weight as

well as in other appropriate units must be reported.

(vii) It may be necessary to conduct separate studies for relevant meta-

bolites (especially toxins), where these products can constitute a

relevant risk to non-target organisms and where their effects

cannot be evaluated by the available results relating to the micro-

organism. Before such studies are performed, the applicant shall

seek agreement of the competent authorities on whether such

studies need to be performed and, if so, the type of study to be

conducted. The information from sections 5, 6 and 7 has to be

taken into account.

(viii) In order to facilitate the assessment of the significance of test

results obtained, the same strain (or recorded origin) of each

relevant species should, where possible, be used in the various

tests specified.

(ix) Tests must be performed unless it can be justified that the non-

target organism will not be exposed to the micro-organism. If it is

justified that the micro-organism does not cause toxic effects or is

not pathogenic or infective to vertebrates or plants, only reaction

to appropriate non-target organisms must be investigated.

8.1.

Effects on birds

Aim of the test

Information on toxicity, infectiveness and pathogenicity to birds must

be reported.

8.2.

Effects on aquatic organisms

Aim of the test

Information on toxicity, infectiveness and pathogenicity to aquatic

organisms must be reported.

8.2.1.

Effects on fish

Aim of the test

Information on toxicity, infectiveness and pathogenicity to fish must

be reported.

8.2.2.

Effects on freshwater invertebrates

Aim of the test

Information on toxicity, infectiveness and pathogenicity to freshwater

invertebrates must be reported.

8.2.3.

Effects on algae growth

Aim of the test

Information on effects on algal growth, growth rate and capacity to

recover must be reported.

8.2.4.

Effects on plants other than algae

Aim of the test

Information on effects on plants other than algae must be reported.

8.3.

Effects on bees

Aim of the test

Information on toxicity, infectiveness and pathogenicity to bees must

be reported.

8.4.

Effects on arthropods other than bees

Aim of the test

Information on toxicity, infectiveness and pathogenicity to arthropods

other than bees must be reported. The selection of the test species

should be related to the potential use of the plant protection products

(e.g. foliar or soil application). Special attention should be given to

organisms used for biological control and organisms playing an

important role in integrated pest management.

8.5.

Effects on earthworms

Aim of the test

Information on toxicity, infectiveness

and

pathogenicity

to

earthworms must be reported.

8.6.

Effects on non-target soil micro-organisms Impact on relevant non-

target micro-organisms and on their predators (e.g. protozoa for

bacterial inoculants) should be reported. Expert judgment is required

to decide whether additional studies are necessary. Such decision will

take into consideration the available information in this and other

sections, in particular data on the specificity of the micro-organism,

and the expected exposure. Useful information may also be available

from the observations carried out in efficacy testing. Special attention

should be given to organisms used in integrated crop management

(ICM).

8.7.

Additional studies

The additional studies might include further acute studies on

additional species or processes (such as sewage systems) or higher tier

studies such as chronic, sub-lethal or reproductive studies on selected

non-target organisms.

Before performing such studies, the applicant shall seek agreement of

the competent authorities on the type of study to be performed.

9. SUMMARY AND EVALUATION OF ENVIRONMENTAL

IMPACT

A summary and evaluation of all data relevant to the environmental

impact, should be carried out according to the guidance given by the

competent authority concerning the format of such summaries and

evaluations. It should include a detailed and critical assessment of

those data in the context of relevant evaluative and decision making

criteria and guidelines, with particular reference to the risks for the

environment and non-target species that may or do arise, and the

extent, quality and reliability of the data base. In particular the

following issues should be addressed

—distribution and fate in the environment, and the time courses

involved,

—identification of non-target species and populations at risk, and the

extent of their potential exposure,

—identification of precautions necessary to avoid or minimise con-

tamination of the environment, and for the protection of non-target

species.

(1) Plant protection products shall not be placed on the

market and used unless these have been authorized by the Director

in accordance with these regulations, except where the intended

use is covered by regulation 18.

(2) The Director shall not, on the grounds that a plant

protection product is not authorized for use in Malta, impede the

production, storage or movement of such products intended for use

in another Member State, provided that

(a)

the product is authorized in another Member State,

and

(b) the inspection requirements laid down by the

Member States in order to ensure compliance with sub-

regulation (1) hereof are satisfied.

(3) Plant protection products must be used properly.

Proper use shall include compliance with the conditions established

in accordance with regulation 4 and specified on the labelling, and

the application of the principles of good plant protection practice

as well as, whenever possible, the principles of integrated pest

control.

(4) Active substances shall not be placed on the market

unless

(a) they are classified, packaged and labelled in

accordance with, The Dangerous Substances (Notification)

Regulations, 2001 (L.N. 318 of 2001) and

(b) where the active substance was not on the market

by 26 July 1993, a dossier has to be forwarded to the Member

States and to the Commission, in accordance with regulation

5, with the declaration that the active substance is intended for

a use specified in regulation 2 (16). This condition shall not

apply to active substances intended for a use under regulation

REQUIREMENTS FOR THE DOSSIER TO BE SUBMITTED FOR THE

AUTHORIZATION OF A PLANT PROTECTION PRODUCT

INTRODUCTION

The information required shall

1.1.

include a technical dossier supplying the information necessary for

evaluating efficacy and the foreseeable risks, whether immediate or

delayed, which the plant protection product may entail for humans,

animals and the environment and containing at least the information

and results of the studies referred to below;

1.2.

where relevant, be generated using test guidelines, according to the

latest adopted version, referred to or described in this Schedule; in the

case of studies initiated before the entry into force of the modification

of Annex II of Directive 414/1991, the information shall be generated

using suitable inter-nationally or nationally validated test guidelines

or, in the absence thereof, test guidelines accepted by the director;

1.3.

in the event of a test guideline being inappropriate or not described, or

where another one than those referred to in this Schedule has been

used, include a justification, which is acceptable to the director for the

guidelines used. In particular, when reference is made in this Schedule

to an EEC Method which consists in the transposal of a method

developed by an international organization (e.g. OECD), the Director

may accept that the required information is generated according to the

latest version of that method if at the initiation of the studies the EEC

Method has not yet been updated;

1.4.

include when required by the director, a full description of test

guidelines used, except if they are referred to or described in this

Schedule, and a full description of any deviations from them

including a justification, which is acceptable to the director, for these

deviations;

1.5.

include a full and unbiased report of the studies conducted as well as a

full description of them or a justification, which is acceptable to the

director where

—particular data and information which would not be necessary

owing to the nature of the product or its proposed uses, are not

provided,

or

—it is not scientifically necessary, or technically possible to supply

information and data.

1.6.

where relevant, have been generated in accordance with the

requirements of Directive 86/609/EEC.

2.1.

Tests and analyses must be conducted in accordance with the prin-

ciples laid down in Directive 2004/10/EC of the European Parliament

and of the Council of 11 February 2004 on the harmonisation of laws,

regulations and administrative provisions relating to the application of

the principles of good laboratory practice and the verification of their

applications for tests on chemical substances.

2.2.

Tests and analyses, required under the provisions of Section 6 points

6.2 to 6.7 of this Schedule, shall be conducted by official or officially

recognized testing facilites or organizations which satisfy at least the

following requirements

—have at their disposal sufficient scientific and technical staff,

having the necessary education, training, technical knowledge and

experience for their assigned functions,

—have at their disposal suitable items of equipment required for

correct performance of the tests and measurements which it claims

to be competent to carry out. This equipment shall be properly

maintained and calibrated where appropriate before being put into

service and thereafter according to an established programme,

—have at their disposal appropriate experimental fields and, where

necessary glasshouses, growth cabinets or storage rooms. The en-

vironment in which the tests are undertaken shall not invalide its

results or adversely effect the required accuracy of measurement,

—make available to all relevant personnel operating procedures and

protocols used for the trials,

—make available, where requested by the director, prior to the

commencement of a test, detailed information on it, containing at

least its location and the plant protection products included in it,

—ensure that the quality of the work performed is appropriate to its

type, range, volume and intended purpose,

— maintain records of all original observations, calculations

and derived data,<calibration records and the final test report as

long as the product concerned authorized in the Community.

2.3.

The Director shall require that officially recognized testing facilities

and organizations, and, where requested, official facilities and organi-

zations

—report to the relevant national authority all detailed information

necessary to demonstrate that they can satisfy the requirements

provided for in point 2.2,

—accept at any time the inspections, which each Member State shall

regularly organize on its territory in order to verify the compliance

with the requirement as laid down in point 2.2.

2.4.

By way of derogation from point 2.1, the Director may apply the

provisions of points 2.2 and 2.3, by extension, to tests and analyses

performed in Malta in order to obtain data on the properties and/or

safety of the preparations with respect to honey-bees and bene-ficial

arthropods other than bees and actually started on or before 31

December 1999.

2.5.

By way of derogation from point 2.1, the Director may apply the

provisions of points 2.2 and 2.3, by extension, to supervised residue

trials performed in Malta in accordance with the provisions of Section

8 ‘Residues in or on treated products, food and feed’ with plant

protection products containing active substances already on the

market two years after notification of the Directive and actually

started on or before 31 December 1997.

2.6.

By way of derogation from point 2.1, for active substances consisting

of micro-organisms or viruses, tests and analyses done to obtain data

on the properties and/or safety with respect to other aspects than

human health, may have been conducted by official or officially

recognised testing facilities or organisations which satisfy at least the

requirements under points 2.2 and 2.3 of the introduction of Schedule

III.

3. The information required shall include the proposed classification and

labelling of the plant protection product in accordance with relevant

Community Directives.

4. In individial cases it may be necessary to require certain information as

provided for in Schedule II, Part A, for formulants. Before such infor-

mation will be required and before possible new studies have to be

performed, all information on the formulant, made available to the

director, will be considered, in particular when

—the use of the formulant is permitted in food, animal feeding stuffs,

medicines or cosmetics in accordance with Community legislation,

or

—a safety data sheet has been submitted for the formulant in

accordance with Council Directive 67/548/EEC.

Chemical preparations

1. Identity of the plant protection product The information provided,

taken together with that provided for the active substance(s), must be

sufficient to precisely identify preparations and define them in terms

of their specification and nature. The information and data referred to,

unless otherwise specified, are required for all plant protection

products.

1.1.

Applicant (name and address, etc.)

The name and address of the applicant (permanent community

address) must be provided as must the name, position, telephone and

telefax number of the appropriate person to contact.

Where in addition, the applicant has an office, agent or representative

in the Member State in which the authorization is being sought, the

name and address of the local office agent or representative should be

provided, as should the name, position, telephone and telefax number

of the appropriate person to contact.

1.2.

Manufacturer of the preparation and the active substance(s) (names

and addresses etc. including location of plants)

The name and address of the manufacturer of the preparation and of

each active substance in the preparation must be provided as must the

name and address of each manufacturing plant in which the

preparation and active substance are manufactured.

A contact point (preferable a central contact point, to include name,

telephone and telefax numbers) must be provided for each.

If the active substance originates from a manufacturer from which

data according to Schedule II had not been submitted previously, a

statement of purity and detailed information on the impurities in

Schedule II have to be provided.

1.3.

Trade name or proposed trade name, and manufacturer's development

code number of the preparation if appropriate

All former and current trade names and proposed trade names and

development code numbers of the preparation as well as the current

names and numbers must be provided. Where trade names and code

numbers referred to, relate to similar but different preparations

(possibly obsolete), full details of the differences, must be provided.

(The proposed trade name may not give rise to confusion with the

trade name of already registered plant protection products.)

1.4.

Detailed quantitative and qualitative information on the composition

of the preparation (active substance(s), and formulants)

1.4.1.

For preparations the following information must be reported

—the content of both technical active substance(s) and pure active

substance(s);

—the content of formulants.

The concentrations should be expressed in terms as provided for in

Directive 92/45/EEC.

1.4.2.

For active substances their ISO common names or proposed ISO

common names and their CIPAC numbers, and, where available, the

EEC (EINECS or ELINCS) numbers must be provided. Where

relevant it must be stated which salt, ester, anion or cation is present.

1.4.3.

Formulants must where possible, be identified both by their chemical

name as given in Annex I to Directive 67/548/EEC, or, if not included

in this Directive, in accordance with both IUPAC and CA nomen-

clature. Their structure or structural formula must be provided. For

each component of the formulants the relevant EEC (EINECS or

ELINCS) number and CAS number where they exist, must be

provided. Where the information provided does not fully identify a

formulant, an appropriate specification must be provided. The trade

name of formulants, where they exist, must also be provided.

1.4.4.

For formulants the function must be given

—adhesive (sticker),

—antifoaming agent,

—antifreeze,

—binder,

—buffer,

—carrier,

—deodorant,

—dispersing agent,

—dye,

—emetic,

—emulsifier,

—fertilizer,

—preservative,

—odourant,

—perfume,

—propellant,

—repellent,

—safener,

—solvent,

—stabilizer,

—synergist,

—thickener,

—wetting agent,

—miscellaneous (specify).

1.5.

Physical state and nature of the preparation (emulsifiable

concentrate, wettable powder, solution etc).

1.5.1.

The type and code of preparation must be designated according to the

‘Catalogue of pesticide formulation types and international coding

system (GIFAP Technical Monograph No 2. 1989)’.

Where a particular preparation is not defined precisely in this publi-

cation a full description of the physical nature and state of the

preparation must be provided, together with a proposal for a suitable

description of the type of preparation and a proposal for its definition.

1.6.

Function (herbicide, insecticide, etc.)

The function must be specified from among the following

—acaricide,

—bactericide,

—fungicide,

—herbicide

—insecticide,

—molluscicide,

—nematicide,

—plant growth regulator,

—repellant,

—rodenticide,

—semio-chemicals,

—talpicide,

—viricide,

—other (must be specified).

2. Physical, chemical and technical properties of the plant protection

product

The extent to which plant protection products for which authorization

is sought, comply with relevant FAO specifications as agreed by the

Group of Experts on Pesticide Specifications, of the FAO Panel of

Experts on Pesticide Specifications, Registration Requirements and

Application Standards, must be stated. Divergences from FAO speci-

fications must be described in detail, and justified.

2.1.

Appearance (colour and odour) A description of both the colour and

odour, if any, and the physical state of the preparation, must be

provided.

2.2.

Explosivity and oxidizing properties

2.2.1.

The explosive properties of preparations must be reported according

to EEC method A 14. Where available thermodynamic information

establishes beyond reasonable doubt that the preparation is incapable

of exothermic reaction, it is sufficient to provide that information as a

justification for not determining the explosive properties of the

preparation.

2.2.2.

Oxidizing properties of preparations which are solids must be

determined and exported according to EEC method A 17. For other

preparations the method used must be justified. The oxidizing prop-

erties do not have to be determined if it can be shown without

reasonable doubt on the basis of thermodynamic information, that the

preparation is incapable of reacting exothermically with combustible

materials.

2.3.

Flash point and other indications of flammability or spontaneous

ignition

The flash point of liquids which contain flammable solvents, must be

determined and reported according to EEC Method A 9. The flamm-

ability of solid preparations and gases must be determined and

reported according to EEC methods A 10, A 11 and A 12 as appro-

priate. The auto-flammability of preparations must be determined and

reported in accordance with EEC methods A 15 or A 16 as appro-

priate, and or, where necessary, according to the UN-Bowes-

Cameron-Cage-Test (UN-Recommendations on the Transport of

Dangerous Goods, Chapter 14, No 14.3.4).

2.4.

Acidity/alkalinity and if necessary pH value

2.4.1.

In the case of preparations which are acidic (pH < 4) or alkaline (pH >

10) the acidity or alkalinity and the pH value must be determined and

reported according to CIPAC Method MT 31 and MT 75 respec-

tively.

2.4.2.

Where relevant (if to be applied as aqueous dilution) the pH of a 1 %

aqueous dilution, emulsion or dispersion of the preparation, must be

determined and reported according to CIPAC Method MT 75.

2.5.

Viscosity and surface tension

2.5.1.

In the case of liquid preparations for Ultra Low Volume use (ULV)

the kinematic viscosity must be determined and reported according to

OECD Test Guideline 114.

2.5.2.

For non newtonian liquids the viscosity must be determined and

reported together with the test conditions.

2.5.3.

In the case of liquid preparations the surface tension has to be

determined and reported according to EEC method A 5.

2.6.

Relative density and bulk density

2.6.1.

The relative density of liquid preparations must be determined and

reported according to EEC Method A 3.

2.6.2.

The bulk (tap) density of preparations which are powders or granules,

must be determined and reported according to CIPAC Methods MT

33, MT 159 or MT 169 as appropriate.

2.7.

Storage—stability and shelf-life: Effects of light, temperature and

humidity on technical characteristics of the plant protection product

The stability of the preparation after storage for 14 days at 54 o C must

2.7.1.

be determined and reported according to CIPAC Method MT 46.

Other times and/or temperatures may be needed (e.g. eight weeks at

40 o C or 12 weeks at 35 o C or 18 weeks at 30 o C) if the preparation is

heat sensitive.

If the active substance content after the heat stability test has

decreased by more than 5 % of the initially found content, the

minimum content shall be declared and information on the

degradation products shall be supplied.

2.7.2.

Additionally in the case of liquid preparations, the effect of low

temperatures on stability, must be determined and reported according

to CIPAC Methods MT 39, MT 48, MT 51 or MT 54 as appropriate.

2.7.3.

The shelf life of the preparation at ambient temperature must be

reported. Where shelf life is less than two years, the shelf life in

months, with appropriate temperature specifications, must be

reported. Useful information is given in GIFAP Monograph No. 17.

2.8.

Technical characteristics of the plant protection product The

technical characteristics of the preparation must be determined to

permit a decision to be made as to its acceptability.

2.8.1.

Wettability

The wettability of solid preparations which are diluted for use (e.g.

wettable powders, water soluble powders, water soluble granules and

water dispersible granules), must be determined and reported

according to CIPAC Method MT 53.3.

2.8.2.

Persistent foaming

The persistence of foaming of preparations to be diluted with water,

must be determined and reported according to CIPAC Method MT 47.

2.8.3.

Suspensibility and suspension stability

—The suspensibility of water dispersible products (e.g. wettable

powders, water dispersible granules, suspension concentrates)

must be determined and reported according to CIPAC Method MT

15, MT 161 or MT 168 as appropriate.

—The spontaneity of dispersion of water dispersible products (e.g.

suspension concentrates and water dispersible granules) must be

determined and reported according to CIPAC Methods MT 160 or

MT 174 as appropriate.

2.8.4.

Dilution stability

The dilution stability of water soluble products must be determined

and reported according to CIPAC Method MT 41.

2.8.5.

Dry sieve test and wet sieve test

In order to ensure that dustable powders have a suitable particle size

distribution for ease of application, a dry sieve test must be conducted

and reported according to CIPAC Method MT 59.1.

In the case of water dispersible products, a wet sieve test must be

conducted and reported according to CIPAC Method MT 59.3 or MT

167 as appropriate.

2.8.6.

Particle size distribution (dustable and wettable powders, granules),

content of dust/fines (granules), attrition and friability (granules)

2.8.6.1. The size distribution of particles in the case of powders, must be

determined and reported according to OECD Method 110.

The nominal size range of granules for direct application must be

determined and reported in accordance with CIPAC MT 58.3, for

water dispersible granules in accordance with CIPAC MT 170.

2.8.6.2. The dust content of granular preparations, must be determined and

reported according CIPAC Method MT 171. If relevant for operator

exposure the particle size of dust must be determined and reported

according to OECD Method 110.

2.8.6.3. The friability and attrition characteristics of granules, must be

determined and reported once internationally agreed methods are

available. Where already data are available they must be reported

together with the method used.

2.8.7.

Emulsifiability, Re-emulsifiability, emulsion stability

2.8.7.1. The emulsifiability, emulsion stability and re-emul-sifiability of

preparations which form emulsions, must be determined and reported

according to CIPAC Methods MT 36 or MT 173 as appropriate.

2.8.7.2. The stability of dilute emulsions and of preparations which are

emulsions, must be determined and reported according to CIPAC

Method MT 20 or MT 173.

2.8.8.

Flowability, pourability (rinsability) and dustability

2.8.8.1. The flowability of granular preparations must be determined and

reported according to CIPAC Mehtod MT 172.

2.8.8.2. The pourability (including rinsed residue) of suspensions (e.g.

suspension concentrates, suspo-emulsions), must be determined and

reported according to CIPAC Method MT 148.

2.8.8.3. The dustability of dustable powders following accelerated storage

according 2.7.1 must be determined and reported according to CIPAC

Method MT 34 or another suitable method.

2.9.

Physical and chemical compatibility with other products including

plant protection products with which its use is to be authorized

2.9.1.

The physical compatibility of tank mixes must be reported based on

in-house test methods. A practical test would be an acceptable alter-

native.

2.9.2.

The chemical compatibility of tank mixes must be determined and

reported except where examination of the individual properties of the

preparations would establish beyond reasonable doubt that there is no

possibility of reaction taking place. In such cases it is sufficient to

provide that information as justification for not practically deter-

mining the chemical compatibility.

2.10.

Adherence and distribution to seeds In the case of preparations for

seed treatment, both distribution and adhesion must be investigated

and reported; in the case of distribution according to CIPAC Method

MT 175.

2.11.

Summary and evaluation of data presented under points 2.1. to 2.10

3. Data on application

3.1.

Field of use envisaged, e.g. field, protected crops, storage of plant

products, home gardening

The field(s) of use, existing and proposed, for preparations containing

the active substance must be specified from among the following

—field use, such as agriculture, horticulture, forestry and viticulture,

—protected crops,

—amenity,

—weed control on non-cultivated areas,

—home gardening,

—house plants,

—plant products storage practice,

—other (specify).

3.2.

Effects on harmful organisms, e.g. contact, inhalation or stomach

poison, fungitoxic or fungistatic, etc., systemic or not in plants

The nature of the effects on harmful organisms must be stated

—contact action,

—stomach action,

—inhalation action,

—fungitoxic action,

—fungistatic action,

—desiccant,

—reproduction inhibitor,

—other (must be specified).

It must be stated whether or not the product is translocated in plants.

3.3.

Details of intended use e.g. types of harmful organisms controlled

and/or plants or plant products to be protected

Details of the intended use must be provided.

Where relevant, effects achieved e.g. sprout suppression, retardation

of ripening, reduction in stem length, enhanced fertilization etc. must

be reported.

3.4.

Application rate

For each method of application and each use, the rate of application

per unit (ha, m 2 ,m 3 ) treated, in terms of g or kg of both preparation

and active substance, must be provided.

Application rates shall normally be expressed in g or kg/ha or in

kg/m 3 and where appropriate in g or kg/tonne; for protected crops and

home gardening use rates shall be expressed in g or kg/100 m 2 or g or

kg/m 3 .

3.5.

Concentration of active substance in material used (e.g. in the diluted

spray, baits or treated seed)

The content of active substance shall be reported, as appropriate, in

g/l, g/kg, mg/kg or in g/tonne.

3.6.

Method of application

The method of application proposed must be described fully, indi-

cating the type of equipment to be used, if any, as well as the type and

volume of diluent to be used per unit of area or volume.

3.7.

Number and timing of applications and duration of protection

The maximum number of applications to be used and their timing,

must be reported. Where relevant the growth stages of the crop or

plants to be protected and the development stages of the harmful

organisms, must be indicated. Where possible the interval between

applications, in days, must be stated.

The duration of protection afforded both by each application and by

the maximum number of applications to be used, must be indicated.

3.8.

Necessary waiting periods or other precautions to avoid phytotoxic

effects on succeeding crops

Where relevant, minimum waiting periods between last application

and sowing or planting of succeeding crops, which are necessary to

avoid phytotoxic effects on succeeding crops, must be stated, and

follow from the data provided under paragraph 6.6.

Limitations on choice of succeeding crops, if any, must be stated.

3.9.

Proposed instructions for use

The proposed instructions for use of the preparation, to be printed on

labels and leaflets, must be provided.

4. Further information on the plant protection product

4.1.

Packaging (type, materials, size etc.), compatibility of the preparation

with proposed packaging materials

4.1.1.

Packaging to be used must be fully described and specified in terms of

the materials used, manner of construction (e.g. extruded, welded

etc.), size and capacity, size of opening, type of closure and seals. It

must be designed in accordance with the criteria and guidelines

specified in the FAO‘Guidelines for the Packaging of Pesticides’.

4.1.2.

The suitability of the packaging, including closures, in terms of its

strength, leakproofness and resistance to normal transport and

handling, must be determined and reported according to ADR

Methods 3552, 3553, 3560, 3554, 3555, 3556 3558, or appropriate

ADR Methods for intermediate bulk containers, and, where for the

preparation child-resistant closures are required, according to ISO

standards 8317.

4.1.3.

The resistance of the packaging material to its contents must be

reported according to GIFAP Monograph No 17.

4.2.

Procedures for cleaning application equipment Cleaning procedures

for both application equipment and protective clothing must be

described in detail. The effectiveness of the cleaning procedure, must

be fully investigated and reported.

4.3.

Re-entry periods, necessary waiting periods or other precautions to

protect man, livestock and the environment

The information provided must follow from and be supported by the

data provided for the active substance(s) and that provided under

sections 7 and 8.

4.3.1.

Where relevant pre-harvest intervals, re-entry periods or withholding

periods necessary to minimize the presence of residues in or on crops,

plants and plant products, or in treated areas or spaces, with a view to

protecting man or livestock, must be specified e.g.

—pre-harvest interval (in days) for each relevant crop,

—re-entry period (in days) for livestock, to areas to be grazed,

—re-entry period (in hours or days) for man to crops, buildings or

spaces treated,

—withholding period (in days) for animal feedingstuffs,

—waiting period (in days), between application and handling treated

products, or

—waiting period (in days), between last application and sowing or

planting succeeding crops.

4.3.2.

Where necessary, in the light of the test results, information on any

specific agricultural, plant health or environmental conditions under

which the preparation shall or shall not be used must be provided.

4.4.

Recommended methods and precautions concerning: handling,

storage, transport or fire

The recommended methods and precautions concerning handling

procedures (detailed) for the storage, at both warehouse and user level

of plant protection products, for their transport and in the event of fire

must be provided. Where available information on combustion

products must be provided. The risks likely to arise and the methods

and procedures to minimize the hazards arising, must be specified.

Procedures to preclude or minimize the generation of waste or

leftovers must be provided.

Where relevant assessment has to be done according to ISO—TR

9122. Where appropriate the nature and characteristics of protective clothing

and equipment proposed must be provided. The data provided must be

sufficient to evaluate the suitability and effectiveness under realistic

conditions of use (e.g. field or glasshouse circumstances).

4.5.

Emergency measures in the case of an accident

Whether arising during transport, storage or use, detailed procedures

to be followed in the event of an emergency, must be provided; and

include

—containment of spillages,

—decontamination of areas, vehicles and buildings,

—disposal of damaged packaging, adsorbents and other materials,

—protection of emergency workers and bystanders,

—first aid measures.

4.6.

Procedures for destruction or decontamination of the plant protection

product and its packaging

Procedures for destruction and decontamination must be developed

for both small quantities (user level) and large quantities (warehouse

level). The procedures must be consistent with provisions in place

relating to the disposal of waste and of toxic waste. The means of

disposal proposed should be without unacceptable influence on the

environment and be the most cost effective and practical means of

disposal feasible.

4.6.1.

Possibility of neutralization

Neutralization procedures (e.g by reaction with alkali to form less

toxic compounds) for use in the event of accidental spillages, must

where they are feasible, be described. The products produced after

neutralization should be practically or theoretically evaluated and

reported.

4.6.2.

Controlled incineration

In many cases the preferred or sole means to safely dispose of active

substances as well as plant protection products containing it,

contaminated materials, or contaminated packaging, is through

controlled incineration in a licensed incinerator.

Where the content of halogens of the active substance(s) in the

preparation is greater than 60 %, the pyrolytic behaviour of the active

substance under controlled conditions (including where relevant

supply of oxygen and defined residence time) at 800 o C and the

content of polyhalogenated dibenzo-p-dioxins and dibenzo-furans in

the products of pyrolysis must be reported. The applicant must

provide detailed instructions for safe disposal.

4.6.3.

Others

Other methods to dispose of plant protection products, packaging and

contaminated materials, where proposed, must be fully described.

Data must be provided for such methods, to establish their

effectiveness and safety.

5. Analytical methods

Introduction

The provisions of this section only cover analytical methods required

for post-registration control and monitoring purposes.

For analytical methods used for generation of data as required in this

Directive or for other purposes the applicant has to provide a justifi-

cation for the method used; where necessary separate guidance will be

developed for such methods on the basis of the same requirements as

defined for methods for post-registration control and monitoring

purposes.

Descriptions of methods must be provided and include details of

equipment, materials and conditions used.

As far as practicable these methods must employ the simplest

approach, involve the minimum cost, and require commonly available

equipment.

For this section the following applies

Impurities

Any component other than the pure active

substance which is present in the active

substance as manufactured (including non-

active isomers) originating from the manufac-

turing process or from degradation during

storage

Relevant impurities

Impurities of toxicological and/or ecotoxico-

logical or environmental concern

Metabolites

Metabolites include products resulting from

degradation or reaction of the active

substance

Relevant metabolites

Metabolites of toxicological and/or ecotoxi-

cological or environmental concern

On request the following samples must be provided

(i) samples of the preparation;

(ii) analytical standards of the pure active substance;

(iii) samples of the active substance as manufactured;

(iv) analytical standards of relevant metabolites and all other

components included in the residue definition;

(v) if available, samples of reference substances for the relevant impu-

rities.

For definitions see Schedule II, Section 4, points 4.1 and 4.2.

5.1.

Methods for the analysis of the preparation

5.1.1.

Methods, which must be described in full, must be provided for the

determination of the active substance in the preparation. In the case of

a preparation containing more than one active substance a method

capable of determining each, in the presence of the other, should be

provided. If a combined method is not submitted, the technical

reasons must be stated. The applicability of existing Cipac methods

must be reported.

5.1.2.

Methods must also be provided for the determination in the

preparation of relevant impurities, if the composition of the

preparation is such that—on the basis of theoretical consideration—

such impurities may be formed by its manufacturing process or from

degradation during storage.

If required, methods for the determination of formulants or

constituents of formulants in the preparation must be submitted.

5.1.3.

Specificity, linearity, accuracy and repeatability

5.1.3.1. Specificity of methods submitted, must be demonstrated and reported.

In addition the extent of interference by other substances present in

the preparation must be determined.

While interferences due to other components may be identified as

systematic errors in the assessment of the accuracy of methods

proposed, an explanation must be provided for any interference

occurring which contribute more than ± 3 % to the total quantity

determined.

5.1.3.2. The linearity of proposed methods over an appropriate range, must be

determined and reported. The calibration range must extend (by at

least 20 %) the highest and lowest nominal content of the analyte in

relevant analytical solutions of the preparation. Duplicate calibration

determinations must be made at three or more concentrations. Alter-

natively, five concentrations, each as single measurements, are

acceptable. Reports submitted must include the equation of the cali-

bration line and the correlation coefficient and representative and

properly labelled documentation from the analysis, e.g. chroma-

tograms.

5.1.3.3.

Accuracy will normally only be required for methods for the determi-

nation of pure active substance and relevant impurities in the preparation.

5.1.3.4. For the repeatability in principle a minimum of five determinations must

be made. The relative standard deviation (% RSD) must be reported.

Outliers identified through an appropriate method (e.g. Dixons or

Grubbs test), may be discarded. Where outliers have been discarded,

that fact must be clearly indicated. An explanation as to the reason for

the occurrence of individual outliers, must be attempted.

5.2.

Analytical methods for the determination of residues

Analytical methods for the determination of residues must be

submitted unless it is justified that the methods already submitted

according to the requirements of Schedule II, Section 4, point 4.2 can

be applied.

The same provisions as provided in Schedule II, Section 4, point 4.2

apply.

6. Efficacy data

General

The data supplied must be sufficient to permit an evaluation of the

plant protection product to be made. In particular it must be possible

to evaluate the nature and extent of benefits that accrue following use

of the preparation, where they exist in comparison to suitable

reference products and damage thresholds, and to define its conditions

of use.

The number of trials to be conducted and reported depends mainly on

factors such as the extent to which the properties of the actieve

substance(s) it contains are known and on the range of conditions that

arise, including variability in plant health conditions, climatic

differences, the range of agricultural practices, the uniformity of the

crops, the mode of application the type of harmful organism and the

type of plant protection product.

Sufficient data must be generated and submitted to confirm that

patterns determined hold for the regions and the range of conditions,

likely to be encountered in the regions concerned, for which its use is

to be recommended. Where an applicant claims that tests in one or

more of the proposed regions of use are unnecessary because

conditions are comparable with those in other regions where tests

have been carried out, the applicant must substantiate the claim for

comparability with documentary evidence.

In order to assess seasonal differences, if any, sufficient data must be

generated and submitted to confirm the performance of the plant

protection product in each agronomically and climatically different

region for each particular crop (or commodity)/harmful organism

combination. Normally trials on effectiveness or phytotoxicity, where

relevant, in at least two growing seasons must be reported.

If to the opinion of the applicant the trials from the first season

adequately confirm the validity of claims made on the basis of extra-

polation of results from other crops, commodities or situations or

from tests with closely similar preparations, a justification, which is

acceptable to the director for not carrying out a second seaons's work

must be provided. Conversely, where, because of climatic or plant

health conditions or other reasons the data obtained in any particular

season are of limited value for the assessment of performance, trials in

one or more further seasons must be conducted and reported.

6.1.

P r e l i m i n a r y t e s t s

Reports in summary form of preliminary tests, including glasshouse

and field studies, used to assess the biological activity and dose range

finding of the plant protection product and of the active substance(s) it

contains, must be submitted when requested by the director. These

reports will provide additional information for the director when it

evaluates the plant production product. Where this information is not

submitted a justification which is acceptable to the director must be

provided.

6.2.

T e s t i n g e f f e c t i v e n e s s

Aim of the tests

The tests shall provide sufficient data to permit an evaluation of the

level, duration and consistency of control or protection or other

intended effects of the plant protection product in comparison to

suitable reference products, where they exist.

Test conditions

Normally a trial consists of three components: test product, reference

product and untreated control.

The performance of the plant protection product must be investigated

in relation to suitable reference products, where they exist. A suitable

reference product is defined as an authorized plant protection product

which has proved a sufficient performance in practice under the agri-

cultural, plant health and environmental (including climatic)

conditions in the area of proposed use. In general, formulation type,

effects on the harmful organisms, working spectrum and method of

application should be close to those of the tested plant protection

product.

Plant protection products must be tested in circumstances where the

target harmful organism has been shown to have been present at a

level causing or known to cause adverse effects (yield, quality, oper-

ational benefit) on an unprotected crop or area or on plants or plant

products which have not been treated or where the harmful organism

is present at such a level that an evaluation of the plant protection

product can be made.

Trials to provide data on plant protection products for control of

harmful organisms must show the level of control of the species of

harmful organisms concerned or of species representative of groups

for which claims are made. Trials must include the different stages of

growth of life cycle of the harmful species, where this is relevant and

the different strains or races, where these are likely to show different

degrees of susceptibility.

Similarly, trials to provide data on plant protection products which are

plant growth regulators, must how the level of effects on the species

to be treated, and include investigation of differences in the response

of a representative sample of the range of cultivars on which its use is

proposed.

In order to clarify the dose response, dose rates lower than the recom-

mended one must be included in some trials in order to enable to

assess whether the recommended rate is the minimum necessary to

achieve the desired effect.

The duration of the effects of treatment must be investigated in

relation to the control of the target organism or effect on the treated

plants or plant products, as appropriate. When more than one

application is recommended, trials must be reported which establish

the duration of the effects of an application, the number of

applications necessary and the desired intervals between them.

Evidence must be submitted to show that the dose, timing and method

of application recommended give adequate control, protection or have

the intended effect in the range of circumstances likely to be

encountered in practical use.

Unless there are clear indications that the performance of the plant

protection production is unlikely to be affected to a significant degree

by environmental factors, such as temperature or rain, an investi-

gation of the effects of such factors on performance must be carried

out and reported, particularly where it is known that the performance

of chemically related products as so affected.

Where proposed label claims include recommendations for the use of

the plant protection product with other plant protection product(s) or

adjuvant(s) information on the performance of the mixture must be

provided.

Test guideline

Trials must be designed to investigate specified issues, to minimize

the effects of random variation between different parts of each site

and to enable statistical analysis to be applied to results amenable to

such analysis. The design, analysis and reporting of trials must be in

accordance with European and Mediterranean Plant Protection Orga-

nization (EPPO) guidelines 152 and 181. The report shall include a

detailed and critical assessment of the data.

The trials must be carried out in accordance to specific EPPO

guidelines, where available, or when a requires so and when the test is

carried out on the territory of this, with guidelines satisfying at least

the requirements of the corresponding EPPO guideline.

A statistical analysis of results amenable to such analysis must be

carried out; where necessary the test guideline used must be adapted

to enable such analysis.

6.3.

I n f o r m a t i o n o n t h e o c c u r r e n c e o r p o s s i b l e

occurrence of the development of resistance

Laboratory data and where it exists, field information relating to the

occurrence and development of resistance or cross-resistance in popu-

lations of harmful organisms to the active substance(s), or to related

actived substances, must be provided. Where such information is not

directly relevant to the uses for which authorization is ought or to be

renewed (different species of harmful organism or different crops), it

must, if available, nevertheless be provided, as it may provide and

indication of the likelihood of resistance developing in the target

population.

Where there is evidence or information to suggest that, in commercial

use, the development of resistance is likely, evidence must be

generated and submitted as to the sensitivity of the population of the

harmful organism concerned to the plant protection product. In such

cases a management strategy designed to minimize the likelihood of

resistance or cross-resistance developing in target species must be

provided.

6.4.

E f f e c t s o n t h e y i e l d o f t r e a t e d p l a n t s o r p l a n t

products in terms of quantity and/or quality

6.4.1.

Effects on the quality of plants or plant product

Aim of the tests

The tests shall provide sufficient data to permit an evaluation of the

possible occurrence of taint or odour or other quality aspects of plants

or plant products after treatment with the plant protection product.

Circumstances in which required

The possibility of the occurrence of taint or odour in food crops must

be investigated and be reported where

—the nature of the products or its use is such that a risk of occurrence

of taint or odour might be expected,

or

—other products based on the same or a closely similar active

ingredient have been shown to present a risk of occurrence of taint

or odour.

The effects of plant protection products on other quality aspects of

treated plants or plant products must be investigated and reported

where

—the nature of the plant protection product or it use could have an

adverse influence on other quality aspects (for example in the case

of use of plant growth regulators close or harvest), or

—other products based on the same or a closely similar active

ingredient have been shown to have an adverse influence on the

quality.

Testing should be conducted initially on the main crops on which the

plant protection product is to be used, at twice the normal rates of

application and using, where relevant, the main methods of

processing. Where effects are observed it is necessary to perform

testing at the normal rate of application.

The extent of investigation necessary on other crops will depend on

their degree of similarity of the main crops already tested, the quantity

and quality of data available on those main crops and how far the

manner of use of the plant protection product and methods of

processing the crops, are similar. It is generally sufficient to perform

the test with the main formulation type to be authorized.

6.4.2.

Effects on transformation processes

Aim of the tests

The tests shall provide sufficient data to permit an evaluation of the

possible occurrence of adverse effects after treatment with the plant

protection product on transformation processes or on the quality of

their products.

Circumstances in which required

When the treated plants or plant products are normally intended for

use in transformation process such as wine making, brewing or bread

making and when at harvest significant residues are present, the possi-

bility of the occurrence of adverse effects must be investigated and

reported where

—there are indications that the use of the plant protection product

could have an influence on the processes involved (for example in

the case of use of plant growth regulators or fungicides close to

harvest),

or

—other products based on the same or a closely similar active

ingredient have been shown to have an adverse influence on these

processes or its products.

It is generally sufficient to perform the test with the main formulation

type to be authorized.

6.4.3.

Effects on the yield of treated plants or plant products

Aim of the tests

The test shall provide sufficient data to permit an evaluation of the

performance of the plant protection product and of possible

occurrence of yield reduction or loss in storage of treated plants or

plant products.

Circumstances in which required

The effects of plant protection products on the yield or yield

components of treated plant products must be determined where

relevant. When treated plants or plant products are likely to be stored

the effect on the yield after storage, including data on starage life

must be determined where relevant.

This information will normally be available from the tests required

under the provisions of point 6.2.

6.5.

P h y t o t o x i c i t y t o t a r g e t p l a n t s ( i n c l u d i n g d i f f e r e n t

cultivars), or to target plant products

Aim of the tests

The test shall provide sufficient data to permit an evaluation of the

performance of the plant protection product and of the possible

occurrence of phytotoxicity after treatment with the plant protection

product.

Circumstances in which required

For herbicides and for other plant protection products for which

adverse effects, however transitory, are seen during the trials,

performed in accordance to point 6.2, the margins of selectivity on

target crops must be established, using twice the recommended rate of

application. Where serious phytotoxic effects are seen, an

intermediate application rate must also be investigated.

Where adverse effects occur, but are claimed to be unimportant in

comparison with the benefits of use or transient, evidence to support

this claim is required. If necessary yield measurement must be

submitted.

The safety of a plant protection product to the main cultivars of the

main crops for which it is recommended must be demonstrated,

including effects of crop growh stage, vigour, and other factors which

may influence suspectibility to damage or injury.

The extent of investigation necessary on other crops will depend on

their degree of similarity to the main crops already tested, the quantity

and quality of data available on those main crops and how far the

manner of use of the plant protection product, if relevant, is similar. It

is generally sufficient to perform the test with the main formulation

type to be authorized.

Where proposed label claims include recommendations for the use of

the plant protection product with other plant protection product(s), the

provisions of the previous paragraphs apply for the mixture.

Test guideline

Observations concerning phytotoxicity must be performed in the tests

provided for under point 6.2.

Where phytotoxic effects are seen, they must be accurately assessed

and recorded in accordance with EPPO guideline 135 or when a

Member State requires so and when the test is carried out on the

territory of this Member State, with guidelines satisfying at least the

requirements of this EPPO guideline.

A statistical analysis of results amenable to such analysis must be

carried out, where necessary the test guideline used must be adapted

to enable such analysis.

6.6.

O b s e r v a t i o n s o n u n d e s i r a b l e o r u n i n t e n d e d s i d e -

effects, e. g. on beneficial and other non-target organisms, on succeeding

crops, other plants or parts of treated plants used for propagating

purposes (e. g. seeds, cuttings, runners)

6.6.1.

Impact on succeeding crops

Aim of the information required

Sufficient data must be reported to permit an evaluation of possible

adverse effects of a treatment with the plant protection product on

succeeding crops.

Circumstances in which required

Where data, generated in accordance with Section 9, point 9.1, shows

that signification residues of the active substance, its metabolites or

degradation products, which have or may have biological activity on

succeeding crops, remain in soil or in plant materials, such as straw or

organic material up to sowing or planting time of possible succeeding

crops, observations must be submitted on effects on the normal range

of succeedings crops.

6.6.2.

Impact on other plants, including adjacent crops

Aim of the information required

Sufficient data must be reported to permit an evaluation of possible

adverse effects of a treatment with the plant protection product on

other plants, including adjacent crops.

Circumstances in which required

Observations must be submitted on adverse effects on other plants,

including the normal range of adjacent crops, when there are indi-

cations that the plant protection product could affect these plants via

vapour drift.

6.6.3.

Impact on treated plants or plant products to be used for propagation

Aim of the information required

Sufficient data must be reported to permit an evaluation of possible

adverse effects of a treatment with the plant protection product on

plants or plant products to be used for propagation.

Circumstances in which required

Observations must be submitted on the impact of plant protection

products on plant parts used for propagation except where the

proposed uses preclude use on crops intended for production of seeds,

cuttings, runners or tubers for planting, as appropriate.

(i) for seeds—viability, germination and vigour;

(ii) cuttings—rooting and growth rates;

(iii) runners—establishment and growth rates;

(iv) tubers—sprouting and normal growth.

Test guideline

Seeds testing shall be done according to ISTA Methods ( 1 ).

( 1 ) International rules for seed testing, 1985. Proceedings of the International Seed Testing Association,Seed Science and Technology, Volume 13, No

2, 1985

6.6.4.

Effects on beneficial and other non-target organisms Any effects,

positive or negative, on the incidence of other harmful organisms,

observed in the tests performed in accordance with the requirements

of this section, shall be reported. Any observed environ-mental effects

must also be reported, especially effects on wildlife and/or beneficial

organisms.

6.7.

S u m m a r y a n d e v a l u a t i o n o f d a t a p r e s e n t e d u n d e r

6.1 to 6.6

A summary of all data and in formations provided under points 6.1 to

6.6 must be provided, together with a detailed and a critical

assessment of the data, with particular reference to the benefits that

the plant protection product offers, adverse effects that do or may

arise and measures necessary to avoid or minimize adverse effects.

7. Toxicological studies

For proper evaluation of the toxicity of preparations sufficient infor-

mation should be available on acute toxicity, irritation and sensiti-

zation of the active substance. If possible, additional information on

mode of toxic action, toxicological profile and all other known toxi-

cological aspects of the active substance should be submitted.

In the context of the influence that impurities and other components

can have on toxicological behaviour, it is essential that for each study

submitted, a detailed description (specification) of the material used,

be provided. Tests must be conducted using the plant protection

product to be authorized.

7.1.

Acute toxicity

The studies, data and information to be provided and evaluated, must

be sufficient to permit the identification of effects following a single

exposure to the plant protection product, to be assessed, and in

particular to establish, or indicate

—the toxicity of the plant protection products,

—toxicity of the plant protection product relative to the active

substance,

—the time course and characteristics of the effect with full details of

behavioural changes and possible gross pathological findings at

post-mortem,

—where possible the mode of toxic action, and

—the relative hazard associated with the different routes of exposure.

While the emphasis must be on estimating the toxicity ranges

involved, the information generated must also permit the plant

protection product to be classified in accordance with Council

Directive 99/45/EEC. The information generated through acute

toxicity testing is of particular value in assessing hazards likely to

arise in accident situations.

7.1.1.

Oral

Circumstances in which required

An acute oral test should always be carried out unless the applicant

can justify to the satisfaction of the director that Article 3.2 of Council

Directive 99/45/EEC can be invoked.

Test guidelines

The test must be carried out in accordance with Directive 92/69/EEC

Method B1 or B1 bis.

7.1.2.

Percutaneous

Circumstances in which required

An acute percutaneous test should always be carried out unless the

applicant can justify to the satisfaction of the director that Article 3.2

of Council Directive 1999/45/EEC can be invoked.

Test guideline

The test must be carried out in accordance with Directive 92/69/EEC

Method B3.

7.1.3.

Inhalation

Aim of the test

The test will provide the inhalation toxicity to rats of the plant

protection product or of the smoke it generates.

Circumstances in which required

The test must be carried out where the plant protection product

—is a gas or liquified gas,

—is a smoke generating formulation or fumigant,

—is used with fogging equipment,

—is a vapour releasing preparation,

—is an aerosol,

—is a powder containing a significant proportion of particles of

diameter <50µm (> 1 % on a weight basis),

—is to be applied from aircraft in cases where inhalation exposure is

relevant,

—contains an active substance with a vapour pressure > 1 10 -2 Pa

and is to be used in enclosed spaces such as warehouses or glass-

houses,

—is to be applied in a manner which generates a significant

proportion of particles or droplets of diameter <50µm(>1% on a

weight basis).

Test guideline

The test must be carried out in accordance with Directive 92/69/EEC

Method B2.

7.1.4.

Skin irritation

Aim of the test

The test will provide the potential of skin irritancy of the plant

protection product including the potential reversibility of the effects

observed.

Circumstances in which required

The skin irritancy of the plant protection product must be determined

except where it is likely, as indicated in the test guideline, that severe

skin effects may be produced or that effects can be excluded.

Test guideline

The test must be carried out in accordance with Directive 92/69/EEC

Method B4.

7.1.5.

Eye irritation

Aim of the test

The test will provide the potential for eye irritation of the plant

protection product, including the potential reversibility of the effects

observed.

Circumstances in which required

Eye irritation tests must be conducted except where it is likely, as

indicated in the test guideline, that severe effects on the eyes may be

produced.

Test guideline

The eye irritation must be determined in accordance with Directive

92/69/EEC Method B5.

7.1.6.

Skin sensitization

Aim of the test

The test will provide sufficient information to assess the potential of

the plant protection product to provoke skin sensitization reactions.

Circumstances in which required

The tests must always be carried out except where the active

substance(s) or co-formulants are known to have sensitizing

properties.

Test guideline

The tests have to be carried out in accordance with Directive

92/69/EEC Method B6.

7.1.7.

Supplementary studies for combinations of plant protection products

Aim of the test

In certain cases it may be necessary to carry out the studies as referred

to under points 7.1.1 to 7.1.6 for a combination of plant protection

products where the product label includes requirements for use of the

plant protection product with other plant protection products and/or

with adjuvants as a tank mix. Decisions as to the need for supple-

mentary studies must be made on a case by case basis, taking into

account the results of the acute toxicity studies of the individual plant

protection products, the possibility for exposure to the combination of

the products concerned and available information or practical

experience with the products concerned or similar products.

7.2.

Data on exposure

When measuring exposure to a plant protection product in the air

within the breathing area of operators, bystanders or workers the

requirements for measuring procedures described in Annex II A to

Council Directive 98/24/EC of 7 April 1998 on the protection of the

health and safety of workers from the risks related to chemical agents

at workhave to be taken into account.

7.2.1.

Operator exposure

The risks for those using plant protection products depend on the

physical, chemical and toxicological properties of the plant protection

product as well as the type of the product (undiluted/diluted), and on

the route, the degree and duration of exposure. Sufficient information

and data must be generated and reported to permit an assessment of

the extent of exposure to the active substance(s) and/or

toxicologically relevant compounds in the plant protection product

likely to occur under the proposed conditions of use. It must also

provide a basis for the selection of the appropriate protective

measures including personal protective equipment to be used by

operators and to be specified on the label.

7.2.1.1.Estimation of operator exposure

Aim of the estimation

An estimation shall be made, using where available a suitable calcu-

lation model, in order to permit an evaluation of the operator exposure

likely to arise under the proposed conditions of use.

Circumstances in which required

An estimation of operator exposure must always be completed.

Estimation conditions

An estimation shall be made for each type of application method and

application equipment proposed for use of the plant protection

product taking account of the requirements resulting from the

implementation of the classification and labelling provisions of

Directive 99/45/EEC for handling the undiluted or diluted product as

well as the different types and sizes of containers to be used, mixing,

loading operations, application of the plant protection product, the

climatic conditions and cleaning and routine maintenance of

application equipment.

At first an estimation shall be made with the assumption that the

operator is not using any personal protective equipment.

Where appropriate, a second estimation shall be made with the

assumption that the operator is using effective and readily obtainable

protective equipment which is feasible to be used by the operator.

Where protective measures are specified on the label, the estimation

will take these into account.

7.2.1.2. Measurement of operator exposure

Aim of the test

The test shall provide sufficient data to permit an evaluation of the

operator exposure likely to arise under the proposed conditions of use.

Circumstances in which required

Actual exposure data for the relevant exposure route(s) must be

reported where the risk assessment indicates that a health-based limit

value is exceeded. This will, for example, be the case when the results

of the estimation of operator exposure provided for under point

7.2.1.1 indicate that

—the Acceptable Operator Exposure Level(s) (AOEL) established in

the context of inclusion of the active substance(s) in Schedule I,

and/or

—the Limit Values established for the active substance and/or toxi-

cologically relevant compound(s) of the plant protection product in

accordance with Council Directive 98/24/EEC and Council Directive

2004/37/EC of the European Parliament and of the Council of 29

April 2004 on the protection of workers from the risks related to

exposure to carcinogens or mutagens at work, may be exceeded.

Actual exposure data must also be reported when no appropriate

calculation model or no appropriate data are available to do the

estimation provided for under point 7.2.1.1.

In cases where dermal exposure is the most important exposure route,

a dermal absorption test or the results of a sub-acute dermal study, if

not already available, may be a useful alternative test to provide data

in order to refine the estimate provided for under point 7.2.1.1.

Test conditions

The test must be done under realistic exposure conditions taking into

account the proposed conditions of use.

7.2.2.

Bystander exposure

Bystanders can be exposed during the application of plant protection

products. Sufficient information and data must be reported to provide

a basis for the selection of appropriate conditions of use, including

the exclusion of bystanders from treatment areas and separation

distances.

Aim of the estimation

An estimation shall be made, using where available a suitable calcu-

lation model in order to permit an evaluation of the bystander

exposure likely to arise under the proposed conditions of use.

Circumstances in which required

An estimation of bystander exposure must always be completed.

Estimation conditions

An estimation of bystander exposure must be made for each type of

application method. The estimation shall be made with the assumption

that bystanders do not use any personal protective equipment.

Measurement of bystander exposure may be required when estimates

indicate a cause for concern.

7.2.3.

Worker exposure

Workers can be exposed following application of plant protection

products, when entering treated fields or premises or handling treated

plants or plant products on which residues remain. Sufficient

information and data must be reported to provide a basis for the

selection of appropriate protective measures, including waiting and

re-entry periods.

7.2.3.1. Estimation of worker exposure

and/or

Aim of the estimation

An estimation shall be made using where available a suitable calcu-

lation model, in order to permit an evaluation of the worker exposure

likely to arise under the proposed conditions of use.

Circumstances in which required

The estimation of worker exposure must always be completed.

Estimation conditions

An estimation of worker exposure must be made for each crop and

task to be carried out.

At first the estimation shall be made using available data on the

exposure to be expected with the assumption that the worker is not

using any personal protective equipment.

Where appropriate, a second estimation shall be made with the

assumption that the worker is using effective and readily obtainable

protective equipment which is feasible to be used.

Where appropriate, a further estimation shall be made using data

generated on the amount of dislodgeable residues under the proposed

conditions of use.

7.2.3.2. Measurement of worker exposure

Aim of the test

The test shall provide sufficient data to permit an evaluation of the

worker exposure likely to arise under the proposed conditions of use.

Circumstances in which required

Actual exposure data for the relevant exposure route(s) must be

reported where the risk assessment indicates that a health-based limit

value is exceeded. This will, for example, be the case where the

results of the estimation of worker exposure provided for under point

7.2.3.1 indicate that

—the AOEL(s) established in the context of inclusion of the active

substance(s) in Schedule I,

—the Limit Values established for the active substance and/or toxi-

cologically relevant compound(s) of the plant protection product in

accordance with Council Directives 98/24/EEC and 2004/37/EEC,

may be exceeded.

Actual exposure data must also be reported when no appropriate

calculation model or no appropriate data are available to do the

estimation provided for under point 7.2.3.1.

Where dermal exposure is the most important exposure route, a

dermal absorption test, if not already available, may be a useful

alternative test to provide data in order to refine the estimate provided

for under point 7.1.3.1.

Test conditions

The test must be done under realistic exposure conditions taking into

account the proposed conditions of use.

7.3.

Dermal absorption

Aim of the test

The test shall provide a measurement of the absorption of the active

substance and toxicologically relevant compounds through the skin.

Circumstances in which required

The study must be conducted when dermal exposure is a significant

exposure route and where the risk assessment indicates that a health-

based limit value is exceeded. This will, for example, be the case

where the results of the estimation or measurement of operator

exposure provided for under points 7.2.1.1 or 7.2.1.2 indicate that

—the AOEL(s) established in the context of inclusion of the active

substance(s) in Schedule I,

and/or

—the limit values established for the active substance and/or toxico-

logically relevant compound(s) of the plant protection product in

accordance with Council Directives 98/24/EEC and 2004/37/EEC

may be exceeded.

Test conditions

In principle data of an in vivo rat skin absorption study must be

reported. If, when the results of the estimation using these in vivo skin

absorption data are incorporated in the risk assessment, there remains

an indication of excessive exposure, it may be necessary to perform

an in vivo comparative absorption study on rat and human skin.

Test guideline

Appropriate elements of OECD guideline 417 are to be used. For the

design of the studies it may be necessary to take into account the

results of the skin absorption studies with the active substance(s).

7.4.

Available toxicological data relating to non-active substances

Where available, a copy of the notification and the safety data sheet

submitted in the context of Directive 67/548/EEC and Commission

Regulation (EC) No 1907/2006 of the European Parliament and of the

Council of 18 December 2006 concerning the Registration,

Evaluation, Authorisation and Restriction of Chemicals (REACH),

establishing a European Chemicals Agency, amending Directive

1999/45/EC and repealing Council Regulation (EEC) No 793/93 and

Commission Regulation (EC) No 1488/94 as well as Council

Directive 76/769/EEC and Commission Directives 91/155/EEC,

93/67/EEC, 93/105/EC and 2000/21/EC must be submitted for each

formulant. All other available information should be submitted.

8. Residues in or on treated products, food and feed

Introduction

The provisions of Schedule II, Section 6, Introduction apply.

8.1.

Metabolism, distribution and expression of residue in plants or

livestock

Aim of the tests

The objectives of these studies are

—to provide an estimate of total terminal residues in the relevant

portion of crops at harvest following treatment as proposed,

—to quantify the rate of degradation and excretion of the total residue

in certain animal products (milk or eggs) and excreta,

—to identify the major components of the total terminal residue in

crops and in edible animal products respectively,

—to indicate the distribution of residues between relevant crop parts

and between relevant edible animal products respectively,

—to quantify the major components of the residue and to show the

efficiency of extraction procedures for these components,

—to generate data from which a decision on the need for livestock

feeding studies as provided for in point 8.3 can be made,

—to decide on the definition and expression of a residue.

Circumstances in which required

Supplementary metabolism studies only need to be performed where

it is not possible to extrapolate from data obtained on the active

substance in accordance to the requirements of Schedule II, Section 6,

points 6.1 and 6.2. This might be the case for crops or for livestock

for which data were not submitted in the framework of inclusion of

the active substance in Schedule I or were not necessary for amending

the conditions of its inclusion in Schedule I or where it could be

expected that a different metabolism will occur.

Test conditions

The same provisions as provided under the corresponding paragraphs

of Schedule II, Section 6, points 6.1 and 6.2 apply.

8.2.

Residue trials

Aim of the tests

The objectives of these studies are

—to quantify the highest likely residue levels in treated crops at

harvest or outloading from store following the proposed good

agricultural practice (GAP),

and

—to determine, when appropriate, the rate of decline of pesticide

deposits.

Circumstances in which required

Supplementary residue trials only need to be performed where it is not

possible to extrapolate from data obtained on the active substance in

accordance to the requirements of Schedule II, Section 6, point 6.3.

This might be the case for special formulations, for special application

methods or for crops for which data were not submitted in the

framework of inclusion of the active substance in Schedule I or were

not necessary for amending the conditions of its inclusion in Schedule

I.

Test conditions

The same provisions as provided under the corresponding paragraphs

of Schedule II, Section 6, point 6.3 apply.

8.3.

Livestock feeding studies

Aim of the tests

The objective of these studies is to determine the residue in products

of animal origin which will result from residues in feedingstuffs or

fodder crops.

Circumstances in which required

Supplementary feeding studies for the purpose of assessing maximum

residue levels for products of animal origin are only required where it

is not possible to extrapolate from data obtained on the active

substance in accordance to the requirements of Schedule II, Section 6,

point 6.4. This might be the case where additional fodder crops are to

be authorized which leads to an increased intake of residues of

livestock for which data were not submitted in the framework of

inclusion of the active substance in Schedule I or were not necessary

for amending the conditions of its inclusion in Schedule I.

Test conditions

The same provisions as provided under the corresponding paragraphs

of Schedule II, Section 6, point 6.4 apply.

8.4.

Effects of industrial processing and/or household preparations

Aim of the tests

The main objectives of these studies are

—to establish whether or not breakdown or reaction products arise

from residues in the raw products during processing which may

require a separate risk assessment,

—to determine the quantitative distribution of residues in the various

intermediate and end products, and to estimate transfer factors,

—to enable a more realistic estimate to be made of dietary intake of

residues.

Circumstances in which required

Supplementary studies only need to be performed where it is not

possible to extrapolate from data obtained on the active substance in

accordance to the requirements of Schedule II, Section 6, point 6.5.

This might be the case for crops for which data were not submitted in

the framework of inclusion of the active substance in Schedule I or

were not necessary for amending the conditions of its inclusion in

Schedule I.

Test conditions

The same provisions as provided under the corresponding paragraphs

of Schedule II, Section 6, point 6.5 apply.

8.5.

Residues in succeeding crops

Aim of the test

The objective of these studies is to permit an evaluation of possible

residues in succeeding crops.

Circumstances in which required

Supplementary studies are only required where it is not possible to

extrapolate from data obtained on the active substance in accordance

to the requirements of Schedule II, Section 6, point 6.6. This might be

the case for special formulations, for special application methods or

for crops for which data were not submitted in the framework of

inclusion of the active substance in Schedule I or were not necessary

for amending the conditions of its inclusion in Schedule I.

Test conditions

The same provisions as provided under the corresponding paragraphs

of Schedule II, Section 6, point 6.6 apply.

8.6.

Proposed maximum residue levels (MRLs) and residue definition

A full justification for the proposed MRLs must be provided,

including, where relevant, full details of the statistical analysis used.

If the metabolism studies submitted in accordance with the provisions

of point 8.1 indicate that the residue definition should be changed

taking into account the actual residue definition and the necessary

judgement as outlined under the corresponding paragraph of Schedule

II, Section 6, point 6.7, a re-evaluation of the active substance may be

necessary.

8.7.

Proposed pre-harvest intervals for envisaged uses, or withholding

periods or storage periods, in the case of post-harvest uses.

A full justification for the proposals must be provided.

8.8.

Estimation of the potential and actual exposure through diet and

other means

Consideration will be given to the calculation of a realistic prediction

of dietary intake. This may be done in a step-wise fashion leading to

an increasingly realistic prediction of intake. Where relevant, other

sources of exposure such as residues arising from the use of

medicines or veterinary drugs have to be taken into account.

8.9.

Summary and evaluation of residue behaviour

A summary and evaluation of all data presented in this Section should

be carried out according to the guidance given by the competent

authority concerning the format of such summaries and evaluations. It

should include a detailed and critical assessment of those data in the

context of relevant evaluative and decision-making criteria and

guidelines, with particular reference to the risks for man and animals

that may or do arise, and the extent, quality and reliability of the data

base.

Where metabolism data have been submitted the toxicological signif-

icance of any non-mammalian metabolites must be addressed.

A schematic diagram should be prepared of the metabolic pathway in

plants and animals with a brief explanation of the distribution and

chemical changes involved if metabolism data have been submitted.

9. Fate and behaviour in the environment

Introduction

(i) The information provided, taken together with that for the active

substance as provided for in Schedule II, must be sufficient to

permit an assessment of the fate and behaviour of the plant

protection product in the environment, and of the non-target

species likely to be at risk from exposure to it.

(ii) In particular, the information provided for the plant protection

product, together with other relevant information, and that

provided for the active substance, should be sufficient to

—specify the hazard symbols, the indications of danger, and

relevant risk and safety phrases for the protection of the envi-

ronment, which are to be included on packaging (containers),

—predict the distribution, fate, and behaviour in the environment

as well as the time courses involved,

—identify non-target species and populations for which hazards

arise because of potential exposure, and

—identify measures necessary to minimize contamination of the

environment and impact on non-target species.

(iii) Where radio-labelled test material is used, the provisions of Schedule

II, Chapter 7, introduction, point (iv) apply.

(iv) Where relevant tests should be designed and data analysed using

appropriate statistical methods.

Full details of the statistical analysis should be reported (e.g. all

point estimates should be given with confidence intervals, exact p-

values should be given rather than stating significant/non

significant).

(v) Predicted environmental concentrations in soil (PEC S ), water

(PEC SW and PEC GW ) and air (PEC A ).

Justified estimates must be made of the expected concentrations of

the active substance and relevant metabolites, degradation and

reaction products, in soil, groundwater, surface water and air,

following use as proposed or already occurring. In addition a

realistic worst-case estimation must be made.

For the purposes of the estimation of such concentrations the

following definitions apply

—Predicted environmental concentration in soil (PEC S )

The level of residues in the top layer of the soil and to which

non-target soil organisms may be exposed (acute and chronic

exposure).

—Predicted environmental concentration in surface water

(PEC SW )

The level of residues, in surface water to which non-target

aquatic organisms may be exposed (acute and chronic

exposure).

—Predicted

environmental

concentration

in

groundwater

(PEC GW )

The level of residues in groundwater.

—Predicted environmental concentration in air (PEC A )

The level of residues in air, to which man, animals and other

non-target organisms may be exposed (acute and chronic

exposure).

For the estimation of these concentrations all relevant information

on the plant protection product and on the active substance must

be taken into account. A useful approach for these estimations is

provided in the EPPO schemes for environmental risk assessment

( 1 ). Where relevant the parameters provided for in this section

should be used.

When models are used for estimation of predicted environmental

concentrations they must

—make a best-possible estimation of all relevant processes

involved taking into account realistic parameters and

assumptions,

—where possible be reliably validated with measurements carried

out under circumstances relevant for the use of the model,

—be relevant to the conditions in the area of use.

The information provided must, where relevant, include that referred

to in Schedule II, Part A, point 7: and

9.1

Fate and behaviour in soil

Where appropriate, the same provisions relating to the information to

be provided on the soil used and on its selection apply as provided for

under Schedule II, point 7.1.

9.1.1.

Rate of degradation in soil

9.1.1.1. Laboratory studies

Aim of the test

The soil degradation studies should provide best possible estimates of

the time taken for degradation of 50 and 90 % (DT 50lab and DT 90lab ) of

the active substance under laboratory conditions.

Circumstances in which required

The persistence and behaviour of plant protection products in soil

must be investigated unless it is possible to extrapolate from data

obtained on the active substance and relevant metabolites, degradation

and reaction products in accordance to the requirements of Schedule

II, point 7.1.1.2. This extrapolation is, for example, not possible for

slow release formulations.

Test conditions

The rate of aerobic and/or anaerobic degradation in soil must be

reported.

The duration of the study is normally 120 days except if more than 90

% of the active substance is degraded before that period expires.

Test guideline

SETAC—Procedures for assessing the environmental fate and

ecotoxicity of pesticides.

9.1.1.2. Field studies

—Soil dissipation studies Aim of the

test

The soil dissipation studies should provide best-possible estimates

of the time taken for dissipation of 50 and 90 % (DT 50f and DT 90f ),

of the active substance under field conditions. Where relevant,

information on relevant metabolites, degradation and reaction

products must be collected.

Circumstances in which required

The dissipation and behaviour of plant protection products in soil

must be investigated unless it is possible to extrapolate from data

obtained on the active substance and relevant metabolites, degra-

dation and reaction products in accordance to the requirements of

Schedule II, point 7.1.1.2. This extrapolation is, for example, not

possible for slow-release formulations.

Test conditions and test guideline

The same provisions as provided under the corresponding

paragraph of Schedule II, point 7.1.1.2.2. apply.

—Soil residue studies Aim of the

test

Soil residue studies should provide estimates of the soil residue

levels at harvest or at time of sowing or planting succeeding crops.

Circumstances in which required

Soil residue studies must be reported unless it is possible to extra-

polate from data obtained on the active substance and relevant

metabolites, degradation and reaction products in accordance with

the requirements of Schedule II, point 7.1.1.2.2. This extrapo-

lation is, for example, not possible for slow-release formulations.

Test conditions

The same provisions as provided under the corresponding

paragraph of Schedule II, point 7.1.1.2.2. apply.

Test guideline

SETAC—Procedures for assessing the environmental fate and

ecotoxicity of pesticides.

—Soil accumulation studies Aim of the

tests

The tests should provide sufficient data to evaluate the possibility

of accumulation of residues of the active substance and of relevant

metabolites, degradation and reaction products.

Circumstances in which required

Soil accumulation studies must be reported unless it is possible to

extrapolate from data obtained on the active substance and

relevant metabolites, degradation and reaction products in

accordance with the requirements of Schedule II, point 7.1.1.2.2.

This extrapolation is, for example, not possible for slow-release

formulations.

Test conditions

The same provisions as provided under the corresponding

paragraph of Schedule II, point 7.1.1.2.2. apply.

Test guideline

SETAC—Procedures for assessing the environmental fate and

ecotoxicity of pesticides.

9.1.2.

Mobility in the soil

Aim of the test

The test should provide sufficient data to evaluate the mobility and

leaching potential of the active substance and relevant metabolites,

degradation and reaction products.

9.1.2.1. Laboratory studies

Circumstances in which required

The mobility of plant protection products in soil must be investigated

unless it is possible to extrapolate from data obtained in accordance

with the requirements of Schedule II, points 7.1.2 and 7.1.3.1. This

extrapolation is, for example, not possible for slow-release formu-

lations.

Test guideline

SETAC—Procedures for assessing the environmental fate and

ecotoxicity of pesticides.

9.1.2.2. Lysimeter studies or field leaching studies

Aim of the tests

The test should provide data on

—the mobility of the plant protection product in soil,

—the potential for leaching to ground water,

—the potential distribution in soils.

Circumstances in which required

Expert judgement will be necessary to decide whether field leaching

studies or lysimeter studies should be carried out, taking into account

the results of degradation and mobility studies and the calculated

PEC s . The type of study to be conducted should be discussed with the

competent authorities.

These studies must be performed unless it is possible to extrapolate

from data obtained on the active substance and relevant metabolites,

degradation and reaction products in accordance with the

requirements of Schedule II, point 7.1.3. This extrapolation is, for

example, not possible for slow release formulations.

Test conditions

The same provisions as provided for under the corresponding

paragraph of Schedule II, point 7.1.3.3 apply.

9.1.3.

Estimation of expected concentrations in soil

PEC s estimations must relate both to a single application at the highest

rate of application for which authorization is sought, and to the

maximum number and highest rates of application for which author-

ization is sought, for each relevant soil tested, and are expressed in

terms of mg of active substance and of relevant metabolites, degra-

dation and reaction products per kg of soil.

The factors to be considered in making PEC s estimations relate to

direct and indirect application to soil, drift, run off, and leaching and

include processes such as volatilization, adsorption, hydrolysis,

photolysis, aerobic and anaerobic degradation. For the purposes of

PEC s calculations, the bulk density of soils can be assumed to be 1,5

g/cm 3 dry weight, while the depth of the soil layer is assumed to be 5

cm for applications at the soil surface and 20 cm when incorporation

in the soil is involved. Where ground cover is present at time of

application, it is to be assumed that 50 % (minimum) of the applied

dose reaches the soil surface unless actual experimental data give

more specific information.

Initial, short-term and long-term PEC s calculations (time weighted

averages) must be provided

—initial: immediately after application,

—short-term: 24 hours, 2 days and 4 days after last application,

—long-term: 7, 28, 50 and 100 days after last application, where

relevant.

9.2.

Fate and behaviour in water

9.2.1.

Estimation of concentrations in groundwater

The groundwater contamination routes have to be defined taking into

account relevant agricultural, plant health, and environmental

(including climatic) conditions.

Suitable estimations (calculations) of predicted environmental

concen-tration in groundwater PEC GW , of active substance and

relevant meta-bolites, degradation and reaction products, must be

submitted.

PEC estimations must relate to the maximum number and highest

rates of application, for which authorization is sought.

Expert judgment is required to decide if additional field tests could

provide useful information. Before performing these studies the

applicant shall seek the agreement of the competent authorities on the

type of study to be performed.

9.2.2.

Impact on water treatment procedures In cases where this information

is necessary in the framework of a conditional authorization as meant

in Schedule VI, Part C, point 2.5.1.2 (b), the information provided

should permit to establish or to estimate effectiveness of water

treatment procedures (drinking water and sewage treatment), and

impact on such procedures. Before performing any studies the

applicant shall seek the agreement of the competent authorities on the

type of information to be provided.

9.2.3.

Estimation of concentrations in surface water

The surface water contamination routes have to be defined taking into

account relevant agricultural, plant health, and environmental

(including climatic) conditions.

Suitable estimations (calculations) of predicted environmental

concen-tration in surface water PEC sw , of active substance and

relevant meta-bolites, degradation and reaction products, must be

submitted.

PEC estimations must relate to the maximum number and highest

rates of application, for which authorization is sought, and be relevant

to lakes, ponds, rivers, canals, streams, irrigation/drainage canals and

drains.

The factors to be considered in making PEC sw estimations relate to

direct application to water, drift, run-off, discharge via drains and

atmospheric deposition, and include processes such as volatilization,

adsorption, advection, hydrolysis, photolysis, biodegradation,

sedimen-tation and re-suspension.

Initial, short-term and long-term PEC sw calculations relevant to static

and slow moving water bodies (time weighted averages) must be

provided

—initial: immediately after application,

—short-term: 24 hours, 2 days and 4 days after last application,

—long-term: 7, 14, 21, 28, and 42 days after last application, where

relevant.

Expert judgment is required to decide if additional field tests could

provide useful information. Before performing these studies the

applicant shall seek the agreement of the competent authorities on the

type of study to be performed.

9.3.

Fate and behaviour in air

Guidance under development.

10. Ecotoxicological studies

Introduction

(i) The information provided, taken together with that for the active

substance(s), must be sufficient to permit an assessment of the

impact on non-target species (flora and fauna), of the plant

protection product, when used as proposed. Impact can result from

single, prolonged or repeated exposure, and can be reversible, or

irreversible.

(ii) In particular, the information provided for the plant protection

product, together with other relevant information, and that

provided for the active substance, should be sufficient to

—specify the hazard symbols, the indications of danger, and

relevant risk and safety phrases for the protection of the envi-

ronment, to be mentioned on packaging (containers),

—permit an evaluation of the short- and long-term risks for non-

target species—populations, communities, and processes as

appropriate,

—permit an evaluation of whether special precautions are

necessary for the protection of non-target species.

(iii) There is a need to report all potentially adverse effects found

during routine ecotoxicological investigations and to undertake

and report such additional studies which shall be necessary to

investigate the mechanisms involved and assess the significance of

these effects.

(iv) In general, much of the data relating to impact on non-target

species, required for authorization of plant protection products,

will have been submitted and evaluated for the inclusion of the

active substance(s) in Schedule I. The information on fate and

behaviour in the environment, generated and submitted in

accordance with points 9.1 to 9.3, and on residue levels in plants

generated and submitted in accordance with point 8 is central to

the assessment of impact on non-target species, in that it provides

information on the nature and extent of potential or actual

exposure. The final PEC estimations are to be adapted according

to the different groups of organisms taking in particular into

consideration the biology of the most sensitive species.

The toxicological studies and information submitted in accordance

with point 7.1 provide essential information as to toxicity to

vertebrate species.

(v) Where relevant, tests should be designed and data analysed using

appropriate statistical methods. Full details of the statistical

analysis should be reported (e.g. all point estimates should be

given with confidence intervals, exact p-values should be given

rather than stating significant/non significant).

(vi) Whenever a study implies the use of different doses, the rela-

tionship between dose and adverse effect must be reported.

(vii) Where exposure data are necessary to decide whether a study has

to be performed, the data obtained in accordance with the

provisions of Schedule III, point 9 should be used.

For the estimation of exposure of organisms all relevant infor-

mation on the plant protection product and on the active substance

must be taken into account. A useful approach for these

estimations is provided in the EPPO/Council of Europe schemes

for environmental risk assessment ( 1 ). Where relevant the

parameters provided for in this section should be used. Where it

appears from available data that the plant protection product is

more toxic as the active substance, the toxicity data of the plant

protection product have to be used for the calculation of relevant

toxicity/exposure ratios.

(viii) In the context of the influence that impurities can have on ecotox-

icological behaviour, it is essential that for each study submitted, a

detailed description (specification) of the material used as

provided for under point 1.4, be provided.

(ix) In order to facilitate the assessment of the significance of test

results obtained the same strain of each relevant species should

where possible be used in the various toxicity tests specified.

( 1 ) OEPP/EPPO (1993). Decision-making schemes for the environmental risk assessment of plant protection products.Bulletin OEPP/EPPO Bulletin

23,1-154 andBulletin 24,1-87.

10.1.

Effects on birds

Possible effects on birds must be investigated except where the possi-

bility that birds will be exposed, directly or indirectly, can be ruled

out such as for use in enclosed spaces or wound healing treatments.

The acute toxicity/exposure ratio (TER a ), the short term dietary toxi-

city/exposure ratio (TER st ) and the long term dietary toxicity/exposure

ratio (TER lt ) must be reported, where

TER a =LD 50 (mg a.s./kg body weight) / ETE (mg a.s./kg body weight)

TER st =LC 50 (mg a.s./kg food) / ETE (mg a.s./kg food)

TER lt =

NOEC (mg a.s./kg food) / ETE (mg a.s./kg food)

where ETE = estimated theoretical exposure.

In the case of pellets, granules or treated seeds the amount of a.s. in

each pellet, granule or seed must be reported as well as the proportion

of the LD 50 for the a.s. in 100 particles and per gram of particles. The

size and shape of pellets or granules must be reported.

In the case of baits the concentration of a.s. in the bait (mg/kg) must

be reported.

10.1.1. Acute oral toxicity

Aim of the test

The test should provide, where possible, LD 50 values, the lethal

threshold dose, time courses of response and recovery, the NOEL, and

must include relevant gross pathological findings.

Circumstances in which required

The acute oral toxicity of preparations must be reported, where TER a

or TER st for the active substance(s) in birds are between 10 and 100 or

where results from mammal testing give evidence of a significantly

higher toxicity of the prepration compared to the active substance

unless it can be justified that it is not likely that birds are exposed to

the plant protection product itself.

Test conditions

The study must be conducted on the most sensitive species identified

in the studies provided for in Schedule II, point 8.1.1 or 8.1.2.

10.1.2. Supervised cage or field trials

Aim of the test

The test will provide sufficient data to evaluate the nature and the

extent of the risk in practical conditions of use.

Circumstances in which required

Where the TER a and TER st are > 100 and when there is no evidence of

risk from any further study on the active substance (e.g. repro-duction

study) no further testing is required. In the other cases, expert

judgement is necessary to decide whether there is a need to carry out

further studies. This expert judgement will take into account, where

relevant, foraging behaviour, repellency, alternative food, actual

residue content in the food, persistence of the compound in the vege-

tation, degradation of the formulated product or treated produce, the

amount of predation of the food, acceptance of bait, granules or

treated seed and the possibility for bioconcentration.

Where TER a and TER st =10 or TER lt =5, cage or field trials must be

conducted and reported unless a final assessment is possible on the

basis of studies according to point 10.1.3.

Test conditions

Before performing these studies the applicant should seek the

agreement of the competent authorities on the type and conditions of

the study to be performed.

10.1.3. Acceptance of bait, granules or treated seeds by birds

Aim of the test

The test will provide sufficient data to evaluate the possibility of

consumption of the protection product or plant products treated with

it.

Circumstances in which required

In the case of seed dressings, pellets, baits and preparations which are

granules and where TER a =10, acceptability (palatability) tests must be

conducted.

10.1.4. Effects of secondary poisoning

Expert judgment is required to decide whether the effects of

secondary poisoning should be investigated.

10.2.

Effects on aquatic organisms

Possible effects on aquatic species must be investigated except where

the possibility that aquatic species will be exposed can be ruled out.

TER a and TER lt must be reported, where

TER a = acute LC 50 (mg a.s./l)/realistic worst case PEC sw (initial or

short-term, in mg a.s./l)

TER lt = chronic NOEC (mg a.s./l)/long term PEC sw (mg a.s./l)

10.2.1. Acute toxicity to fish, aquatic invertebrates or effects on algal growth

Circumstances in which required

In principle tests should be carried out on one species from each of

the three groups of aquatic organisms as referred to in Schedule II,

point 8.2 (fish, aquatic invertebrates and algae) in case the plant

protection product itself can contaminate water. However where the

available information permits to conclude that one of these groups is

clearly more sensitive, tests on only the most sensitive species of the

relevant group have to be performed.

The test must be performed where

—the acute toxicity of the plant protection product can not be

predicted on the basis of the data for the active substance which is

especially the case if the formulation contains two or more active

substances or formulants such as solvents, emulgators, surfactants,

dispersants, fertilizers which are able to increase the toxicity in

comparison with the active substance, or

—the intended use includes direct application on water unless

suitable studies referred to under point 10.2.4 are available.

Test conditions and test guidelines

The relevant provisions as under the corresponding paragraphs of

Schedule II, points 8.2.1, 8.2.4 and 8.2.6 apply.

10.2.2. Microcosm or mesocom study

Aim of the test

The tests must provide sufficient data to evaluate the essential impact

on aquatic organisms under field conditions.

Circumstances in which required

Where TER a =100 or where TER lt =10, expert judgment must be used

to decide whether a microcosm or mesocom study is appropriate. This

judgment will take into account the results of any additional data over

and above those required by the provisions of Schedule II, point 8.2

and of point 10.2.1.

Test conditions

Before performing these studies the applicant shall seek the

agreement of the competent authorities on the specific aims of the

study to be performed and consequently on the type and conditions of

the study to be performed.

The study should include at least the highest likely exposure rate,

whether from direct applicaiton, drift, drainage or run-off. The

duration of the study must be sufficient to permit evaluation of all

effects.

Test guideline

Appropriate guidelines are included in

Setac—Guidance document on testing procedures for pesticides in

freshwater mesocosms/Workshop Huntingdon, 3 and 4 July 1991

or

Freshwater field tests for hazard assessment of chemicals—European

Workshop on Freshwater Field Tests (EWOFFT).

10.2.3. Residue data in fish

Aim of the test

The test will provide sufficient data to evaluate the potential for

occurrence of residues in fish.

Circumstances in which required

In general data are available from bioconcentration studies in fish.

Where bioconcentration has been observed in the study performed in

accordance with Schedule II, point 8.2.3 expert judgement is required

to decide whether a long-term microcosm or mesocosm study has to

be carried out in order to establish the maximum residues likely to be

encountered.

Test guideline

Setac—Guidance document on testing procedures for pesticides in

freshwater mesocosms/Workshop Huntingdon, 3 and 4 July 1991.

10.2.4. Additional studies

The studies referred to in Schedule II, points 8.2.2 and 8.2.5 shall be

required for particular plant protection products where it is not

possible to extrapolate from data obtained in the corresponding

studies on the active substance.

10.3.

Effects on terrestrial vertebrates other than birds

Possible effects on wild vertebrate species must be investigated

except where it can be justified that it is not likely that terrestrial

vertebrates other than birds are exposed, directly or indirectly. TER a ,

TER st and TER lt must be reported, where

TER a =LD 50 (mg a.s./kg body weight) / ETE (mg a.s./kg body

weight)

TER st = subchronic NOEL (mg a.s./kg food) / ETE (mg a.s./kg food)

TER lt = chronic NOEL (mg a.s./kg food) / ETE (mg a.s./kg food)

where ETE = estimated theoretical exposure.

In principle the evaluation sequence for the assessment of risks to

such species is similar to that for birds. In practice it is not often

necessary to perform further testing as the studies conducted in

accordance with the requirements of Schedule II, point 5 and

Schedule III, point 7 would provide the required information.

Aim of the test

The test will provide sufficient information to evaluate the nature and

the extent of risks for terrestrial vertebrates other than birds in

practical conditions of use.

Circumstances in which required

Where TER a and TER st > 100 and where there is no evidence of risk

from any further study no further testing is required. In the other

cases, expert judgment is necessary to decide whether there is a need

to carry out further studies. This expert judgment will take into

account, where relevant, foraging behaviour, repellency, alternative

food, actual residue content in the food, persistence of the compound

in the vege-tation, degradation of the formulated product or treated

produce, the amount of predation of the food, acceptance of bait,

granules or treated seed and the possibility for bioconcentration.

Where TER a and TER st =10 or TER lt =5 cage or field trials or other

appropriate studies must be reported.

Test conditions

Before performing these studies the applicant shall seek the

agreement of the competent authorities on the type and conditions of

the study to be performed and whether the effects of secondary

poisoning should be investigated.

10.4.

Effects on bees

The possible effects on bees must be investigated except where the

product is for exclusive use in situations where bees are not likely to

be exposed such as

—food storage in enclosed spaces,

—non-systemic seed dressings,

—non-systemic preparations for application to soil,

—non-systemic dipping treatments for transplanted crops and bulbs,

—wound sealing and healing treatments,

—rodenticidal baits,

—use in glasshouses without pollinators.

The hazard quotients for oral and contact exposure (Q HO and Q HC ),

must be reported

Q HO = dose/oral LD 50 (µg a.s. per bee)

Q HC = dose/contact LD 50 (µg a.s. per bee)

where

dose= the maximum application rate, for which authorization is

sought, in g of active substance per hectare.

10.4.1. Acute oral and contact toxicity

Aim of the test

The test should provide the LD 50 values (by oral and contact

exposure).

Circumstances in which required

Testing is required if

—the product contains more than one active substance;

—the toxicity of a new formulation cannot be reliably predicted to be

either the same or lower than a formulation tested according to the

provisions of Schedule II, point 8.3.1.1 or of this point.

Test guideline

The test must be carried out according to EPPO Guideline 170.

10.4.2. Residue test

Aim of the test

The test should provide sufficient information to evaluate possible

risks to foraging bees from residual traces of plant protection products

remaining on crops.

Circumstances in which required

Where Q HC =50, expert judgment is required to decide whether the

effect of residues must be determined unless there is evidence that

there are no significant residual traces remaining on crops which

could affect foraging bees or unless sufficient information is available

from cage, tunnel or field tests.

Test conditions

The median lethal time (LT 50 ) (in hours) following 24-hour exposure

to residues on leaves aged during eight hours must be determined, and

reported. Where LT 50 is more than eight hours, no further testing is

required.

10.4.3. Cage tests

Aim of the test

The test should provide sufficient information to evaluate possible

risks from the plant protection product for bee survival and behaviour.

Circumstances in which required

Where Q HO and Q HC are < 50, further testing is not required except if

significant effects are observed in the bee brood feeding test or if

there are indications for indirect effects such as delayed action or

modifi-cation of bee behaviour, in those cases cage and/or field tests

shall be carried out.

Where Q HO and Q HC are > 50, cage and/or field testing is required.

Where field testing is conducted and reported in accordance with

point 10.4.4, it is not necessary to conduct cage tests. However, cage

tests where conducted, must be reported.

Test conditions

The test should be carried out using healthy bees. If bees have been

treated, e.g. with a varroacide, it is necessary to wait for four weeks

before using the colony.

Test guideline

The tests must be conducted in accordance with EPPO Guideline 170.

10.4.4. Field tests

Aim of the test

The test should provide sufficient information to evaluate possible

risks from the plant protection product on bee behaviour, colony

survival and development.

Circumstances in which required

Field tests must be conducted where on the basis of expert judgement,

taking into account the proposed manner of use and the fate and

behaviour of the active substance, significant effects are observed in

cage testing.

Test conditions

The test should be carried out using healthy honeybee colonies of

similar natural strength. If bees have been treated, e.g. with a

varroacide, it is necessary to wait for four weeks before using the

colony. The tests shall be conducted under conditions reasonably

representative of the proposed use.

Special effects (larval toxicity, long residual effect, disorienting

effects on bees) identified by the field tests may require further

investigation using specific methods.

Test guideline

The tests must be conducted in accordance with EPPO Guideline 170.

10.4.5. Tunnel tests

Aim of the test

The test should provide sufficient information to evaluate the impact

on bees resulting from feeding on contaminated honey dew or

flowers.

Circumstances in which required

Where it is not possible to investigate certain effects in cage or field

trials, a tunnel test should be carried out, e.g. in the case of plant

protection products intended for control of aphids and other sucking

insects.

Test conditions

The test should be carried out using healthy bees. If bees have been

treated, e.g. with a varroacide, it is necessary to wait for four weeks

before using the colony.

Test guideline

The test must be carried out in accordance with EPPO Guideline 170.

10.5.

Effects on arthropods other than bees The effects of plant

protection products on non-target terrestrial arthropods (e.g. predators

or parasitoids of harmful organisms) must be investigated. The

information obtained for these species can also be used to indicate the

potential for toxicity to non-target species inha-biting the same

environment.

10.5.1. Laboratory, extended laboratory and semi-field tests

Aim of the test

The test should provide sufficient information to evaluate the toxicity

of the plant protection product for selected arthropod species that are

relevant to the intended use of the product.

Circumstances in which required

Testing is not required where severe toxicity (> 99 % effect on the

organisms compared to control) can be predicted from relevant

available data or where the plant protection product is for exclusive

use in situations where non-target arthropods are not exposed such as

—food storage in enclosed spaces,

—wound sealing and healing treatments,

—rodenticidal baits.

Testing is required when significant effects on the organisms in

comparison with the control are reported in the laboratory tests at the

maximum recommended dose, conducted in accordance with the

requirements of Schedule II, point 8.3.2. Effects on a particular test

species are considered to be significant when they exceed the

threshold values as defined in the EPPO schemes for the environmen-

tal risk assessment unless species-specific threshold values are

defined in the respective test guidelines.

Testing is also required if

—the product contains more than one active substance,

—the toxicity of a new formulation cannot be reliably predicted to be

either the same or lower than a formulation tested according to the

provisions of Schedule II, point 8.3.2 or of this point,

—on the basis of the proposed manner of use or on the basis of the

fate and behaviour continued or repeated exposure can be

anticipated,

—there is a significant change in the proposed use, e.g. from arable

crops to orchards, and species relevant to the new use have not

previously been tested,

—there is an increase in the recommended application rate, above that

previously tested under Schedule II.

Test conditions

Where significant effects were observed in the studies performed in

accordance with the requirements of Schedule II, point 8.3.2, or in the

case of change of use such as arable crops to orchards, the toxicity of

two additional relevant species must be investigated and reported.

These must be different to the relevant species already tested under

Schedule II, point 8.3.2.

For a new mixture or formulation, the toxicity should initially be

assessed using the two most sensitive species as identified in studies

already performed for which the threshold values were exceeded but

effects still remain below 99 %. This will enable a comparison to be

made; if it significantly more toxic two species relevant to its

proposed use must be tested.

Testing must be conducted at a rate equivalent to the maximum rate of

application for which authorization is sought. A sequential testing

approach should be adopted, i.e. laboratory, and if necessary extended

laboratory and/or semi-field.

Where there will be more than one application per season, the product

should be applied at twice the recommended application rate unless

this information is already available from studies performed in

accordance with Schedule II, point 8.3.2.

Where on the basis of the proposed manner of use or on the basis of

the fate and behaviour continued or repeated exposure can be

anticipated (such as the product is to be applied more than three times

per season with a re-application of 14 days or less), expert judgment

is required to examine whether further testing is required, beyond

initial laboratory testing, which will reflect the proposed use pattern.

These tests shall be performed in the laboratory or under semi-field

conditions. When the test is done in the laboratory a realistic substrate

such as plant material or a natural soil should be used.

However it may be more appropriate to carry out field tests.

Test guideline

Where relevant testing should be done according to appropriate

guidelines which satisfy as least the requirements for testing as

included in Setac - Guidance document on regulatory testing

procedures for pesticides with non-target arthropods.

10.5.2. Field tests

Aim of the test

The tests should provide sufficient information to evaluate the risk of

the plant protection product for arthropods under field conditions.

Circumstances in which required

Where significant effects are seen following laboratory and semi-field

exposure, or where on the basis of the proposed manner of use or on

the basis of the fate and behaviour continued or repeated exposure can

be anticipated expert judgment is required to examine whether more

extensive testing is necessary to permit an accurate risk assessment.

Test conditions

The tests must be conducted under representative agricultural

conditions and in accordance with the proposed recommendations for

use, resulting in a realistic worst case study.

A toxic standard should be included in all tests.

Test guideline

Where relevant testing should be done according to appropriate

guidelines which satisfy at least the requirements for testing as

included in Setac—Guidance document on regulatory testing

procedures for pesticides with non-target arthropods.

10.6.

Effects on earthworms and other soil non-target macro-

organisms, believed to be at risk

10.6.1. Effects on earthworms

The possible impact on earthworms must be reported except where it

can be justified that it is not likely that earthworms are exposed,

directly or indirectly.

TER a and TER lt must be reported where

TER a =LC 50 (mg a.s./kg)/realistic worst case PEC s (initial or short-

term, in mg a.s./kg)

TER lt = NOEC (mg a.s./kg)/long term PECs (mg a.s./kg).

10.6.1.1. Acute toxicity tests

Aim of the test

The test should provide the LC 50 , where possible the highest concen-

tration causing no mortality and the lowest concentration causing 100

% mortality and must include observed morphological and beha-

vioural effects.

Circumstances in which required

These studies are only required where

—the product contains more than one active substance,

—the toxicity of a new formulation cannot be reliably predicted from

the formulation tested according to the provisions of Schedule II,

point 8.4 or of this point.

Test guideline

The tests must be conducted in accordance to OECD Method 207.

10.6.1.2. Tests for sublethal effects

Aim of the test

The test should provide the NOEC and the effects on growth, repro-

duction and behaviour.

Circumstances in which required

These studies are only required where

—the product contains more than one active substance,

—the toxicity of a new formulation cannot be reliably predicted from

the formulation tested according to the provisions of Schedule II,

point 8.4 or of this point,

—there is an increase in the recommended application rate, above that

previously tested.

Test conditions

The same provisions as under the corresponding paragraphs of Schedule

II, point 8.4.2 apply.

10.6.1.3. Field studies

Aim of the test

The test should provide sufficient data to evaluate the effects on

earthworms in field conditions.

Circumstances in which required

Where TER lt < 5 a field study to determine effects under practical field

conditions must be conducted and reported.

Expert judgment is required to decide whether residue contents of

earthworms should be investigated.

Test conditions

Fields selected shall have a reasonable earthworm population.

The test must be carried out at the maximum proposed application

rate. A toxic reference product must be included in the test.

10.6.2. Effects on other soil non-target macro-organisms

Aim of the test

The test should provide sufficient data to evaluate the impact of the

plant protection product on macro-organisms that contribute to the

breakdown of dead plant and animal organic matter.

Circumstances in which required

Testing is not required where in accordance with Schedule III, point

9.1, it is evident that DT 90 values are less than 100 days, or the nature

and manner of use of the plant protection product are such that

exposure does not occur or when data from studies on the active

substance performed in accordance with the provisions of Schedule II,

points 8.3.2, 8.4 and 8.5 indicate that there is no risk for soil

macrofauna, earthworms or soil microflora.

Impact on organic matter breakdown must be investigated and

reported, where the DT 90f values determined in field dissipation

studies (point 9.1) are > 365 days.

10.7.

Effects on soil non-target micro-organisms

10.7.1. Laboratory testing

Aim of the test

The test should provide sufficient data to evaluate the impact of the

plant protection product on soil microbial activity in terms of nitrogen

transformation and carbon mineralization.

Circumstances in which required

Where the DT 90f values determined in field dissipation studies (point

9.1) are > 100 days, impact on soil non-target micro-organisms must

be investigated through laboratory testing. Testing is, however, not

required if in the studies performed in accordance with the provisions

of Schedule II, point 8.5 deviations from control values in terms of

metabolic activity of the microbial biomass after 100 days is < 25 %,

and such data are relevant to the uses, nature, and properties of the

particular preparation to be authorized.

Test guideline

Setac—Procedures for assessing the environmental fate and

ecotoxicity of pesticides.

10.7.2. Additional testing

Aim of the test

The test should provide sufficient data to evaluate the impact of the

plant protection product under field conditions on microbial activitiy.

Circumstances in which required

Where at the end of 100 days, measured activity deviates by more

than 25 % from the control, in the laboratory testing further testing in

the laboratory, under glass and/or in the field may be necessary.

10.8.

Available data from biological primary screening in summary

form

A summary of available data from preliminary tests used to assess the

biological activity and dose range finding whether positive or

negative, which provides information with respect to possible impact

on non/target species, both flora and fauna, must be provided,

together with a critical assessment as to its relevance to potential

impact on non-target species.

11. Summary and evaluation of points 9 and 10

A summary and evaluation of all data presented in points 9 and 10

should be carried out according to the guidance given by the

competent authority concerning the format of such summaries and

evaluations. It should include a detailed and critical assessment of

those data in the context of relevant evaluative and decision making

criteria and guidelines, with particular reference to the risks for the

environment and non-target species that may or do arise, and the

extent, quality and reliability of the data base. In particular the

following issues should be addressed

—predicting distribution and fate in the environment, and the time

courses involved,

—identifying non-target species and populations at risk, and

predicting the extent of potential exposure,

—evaluation as to the short- and long-term risks for non-target

species—populations, communities, and processes—as appro-

priate,

—evaluation as to the risk of fish kills, and fatalities in large verte-

brates, or terrestrial predators, regardless of effects at population

or community level, and

—identification of precautions necessary to avoid or minimize con-

tamination of the environment, and for the protection of non-target

species.

12. Further information

12.1.

Information on authorizations in other countries

12.2.

Information on established maximum residue limits (MRL) in other

countries

12.3.

Proposals including justification for the classification and labelling

proposed in accordance with Directive 67/548/EEC and Directive

99/45/EEC

—Hazard symbol(s)

—Indications of danger

—Risk phrases

—Safety phrases

12.4.

Proposals for risk and safety phrases in accordance with regulation 15

(1), (g) and (h) and proposed label

12.5.

Specimens of proposed packaging

PART B

Introduction

(i) This Part provides data requirements for the authorisation of a plant

protection product based on preparations of micro-organisms including

viruses.

The term‘micro-organism’as defined in the introduction of Schedule II, Part

B, also applies to Schedule III, Part B.

(ii) Where relevant, data should be analysed using appropriate statistical

methods. Full details of the statistical analysis should be reported (e.g. all

point estimates should be given with confidence intervals, exact p-values

should be given rather than stating significant/non significant).

(iii) Pending the acceptance of specific guidelines at international level, the

information required shall be generated using test guidelines accepted by

the director (e.g. USEPA guideline ( 1 )); where appropriate test guidelines as

described in Schedule II, Part A, should be adapted in such a way that they

are appropriate for micro-organisms. Testing should include viable and, if

appropriate, non-viable micro-organisms, and a blank control.

(iv) Whenever a study implies the use of different doses, the relationship

between dose and adverse effect must be reported.

(v) Where testing is done, a detailed description (specification) of the material

used and its impurities, according to the provisions of section 1, point 1.4,

must be provided.

(vi) In cases where a new preparation is to be dealt with, extrapolation from

Schedule II, Part B, could be acceptable, provided that all the possible

effects of the formulants and other components, especially on pathogenicity

and infectiveness, are also evaluated.

( 1 )USEPA

Microbial

Pesticide

Test

Guidelines,

OPPTS

1996(http://www.epa.gov/oppbppd1/biopesticides/guidelines/series885.htm).

1. IDENTITY OF THE PLANT PROTECTION PRODUCT The

information provided, taken together with that provided for the micro-

organism(s), must be sufficient to precisely identify and define

preparations. The information and data referred to, unless otherwise

specified, are required for all plant protection products. This is with

the view to identify if any factor could alter the properties of the

micro-organism as a plant protection product in comparison to the

micro-organism as such, which is treated in Annex II, Part B, to

Directive 91/414/EEC.

1.1.

Applicant

The name and address of the applicant (permanent community

address) must be provided as must the name, position, telephone and

fax number of the appropriate person to contact.

Where, in addition, the applicant has an office, agent or representative

in the Member State in which the authorisation is being sought, the

name and address of the local office, agent or representative should be

provided, as should the name, position, telephone and fax number of

the appropriate person to contact.

1.2.

Manufacturer of the preparation and the micro-organism(s)

The name and address of the manufacturer of the preparation and of

each micro-organism in the preparation must be provided as must the

name and address of each manufacturing plant in which the

preparation and micro-organism are manufactured.

A contact point (preferable a central contact point, to include name,

telephone and fax numbers) must be provided for each manufacturer.

If the micro-organism originates from a producer from which data

according to Schedule II, Part B, had not been submitted previously,

detailed information on the name and species description, as required

in Schedule II, Part B, section 1.3, and on impurities, as required in

Schedule II, Part B, section 1.4, have to be provided.

1.3.

Trade name or proposed trade name, and manufacturer's devel-

opment code number of the preparation if appropriate

All former and current trade names and proposed trade names and

development code numbers of the preparation referred to in the

dossier as well as the current names and numbers must be provided.

Full detail of any differences must be provided. (The proposed trade

name must not give rise to confusion with the trade name of already

authorised plant protection products.)

1.4.

Detailed quantitative and qualitative information on the compo-

sition of the preparation

(i) Each micro-organism that is subject to the application should be

identified and named at the species level. The micro-organism

should be deposited at a recognised culture collection and given

an accession number. The scientific name must be stated, as well

as the group assignment (bacteria, virus, etc.) and any other

denomination relevant to the micro-organism (e.g. strain,

serotype). In addition, the development phase of the micro-

organism (e.g. spores, mycelium) in the marketed product shall

be stated.

(ii) For preparations the following information must be reported

—the content of the micro-organism(s) in the plant protection

product and the content of the micro-organism in the material

used for manufacturing of plant protection products. These

must include the maximum, minimum and nominal content of

the viable and non-viable material,

—the content of formulants,

—the content of other components (such as by-products,

condensates, culture medium, etc.) and contaminating micro-

organisms, derived from production process.

The contents should be expressed in terms as provided for in

Article 6(2) of Directive 99/45/EEC for chemicals and appro-

priate terms for micro-organisms (number of active units per

volume or weight or any other manner that is relevant to the

micro-organism).

(iii) Formulants must where possible, be identified either by their

chemical name as given in Annex I to Directive 67/548/EEC, or,

if not included in this Legal Notice, in accordance with both

IUPAC and CA nomenclature. Their structure or structural

formula must be provided. For each component of the formulants

the relevant EC (Einecs or Elincs) number and CAS number

where they exist, must be provided. Where the information

provided does not fully identify a formulant, an appropriate speci-

fication must be provided. The trade name of formulants, where

they exist, must also be provided.

(iv) For formulants the function must be given

—adhesive (sticker)

—antifoaming agent

—antifreeze

—binder

—buffer

—carrier

—deodorant

—dispersing agent

—dye

—emetic

—emulsifier

—fertiliser

—odorant

—parfume

—preservative

—propellant

—repellent

—safener

—solvent

—stabiliser

—synergist

—thickener

—wetting agent

—miscellaneous (specify).

(v) Identification of contaminating micro-organisms and other

components derived from production process.

Contaminating micro-organisms must be identified as outlined in

Schedule II, Part B, section 1, point 1.3.

Chemicals (inert components, by-products, etc.) must be

identified as outlined in Schedule II, Part A, section 1, point 1.10.

Where the information provided does not fully identify a

component, such as condensate, culture medium, etc., detailed

information on the composition must be provided for each such

component.

1.5.

Physical state and nature of the preparation

The type and code of preparation must be designated according to the

‘Catalogue of pesticide formulation types and international coding

system (GIFAP Technical Monograph No 2, 1989)’.

Where a particular preparation is not defined precisely in this publi-

cation a full description of the physical nature and state of the

preparation must be provided, together with a proposal for a suitable

description of the type of preparation and a proposal for its definition.

1.6.

Function

The biological function must be specified from among the following

—control of bacteria,

—control of fungi,

—control of insects,

—control of mites,

—control of molluscs,

—control of nematodes,

—control of weeds,

—other (must be specified).

2. PHYSICAL, CHEMICAL AND TECHNICAL PROPERTIES OF

THE PLANT PROTECTION PRODUCT

The extent to which plant protection products for which authorisation

is sought comply with relevant FAO specifications, as agreed by the

Group of Experts on Pesticide Specification of the FAO Panel of

Experts on Pesticide Specifications, Registration Requirements and

Application Standards, must be stated. Divergences from FAO speci-

fications must be described in detail, and justified.

2.1.

Appearance (colour and odour) A description of both the colour and

odour, if any, and the physical state of the preparation, must be

provided.

2.2.

Storage stability and shelf-life

2.2.1.

Effects of light, temperature and humidity on technical characteristics

of the plant protection product

(i) The physical and biological stability of the preparation at the

recommended storage temperature including information on the

growth of contaminating micro-organisms must be determined

and reported. The conditions under which the test has been

performed must be justified.

(ii) Additionally in the case of liquid preparations, the effect of low

temperatures on physical stability, must be determined and

reported according to CIPAC ( 1 ) Methods MT 39, MT 48, MT 51

or MT 54 as appropriate.

(iii) The shelf life of the preparation at the recommended storage

temperature must be reported. Where shelf life is less than two

years, the shelf life in months, with appropriate temperature

speci-fications, must be reported. Useful information is given in

GIFAP ( 2 ) Monograph No 17.

2.2.2.

Other factors affecting stability Effect of exposure to air, packaging,

etc., on the product stability must be explored.

2.3.

Explosivity and oxidising properties

Explosivity and oxidising properties will be determined as defined in

Schedule III, Part A, section 2, point 2.2, unless it can be justified that

it is technically or scientifically not necessary to perform such studies.

( 1 ) Collaborative International Pesticides Analytical Council.

( 2 ) International Group of National Pesticide Manufacturers' Associations.

2.4.

Flash point and other indications of flammability or spontaneous

ignition

Flash point and flammability must be determined, as defined in Schedule

III, Part A, section 2, point 2.3, unless it can be justified that it is

technically or scientifically not necessary to perform such studies.

2.5.

Acidity, alkalinity and if necessary pH value Acidity, alkalinity and

pH will be determined as defined in Schedule III,

Part A, section 2, point 2.4, unless it can be justified that it is tech-

nically or scientifically not necessary to perform such studies.

2.6.

Viscosity and surface tension

Viscosity and surface tension will be determined as defined in Schedule

III, Part A, section 2, point 2.5, unless it can be justified that it is

technically or scientifically not necessary to perform such studies.

2.7.

Technical characteristics of the plant protection product The

technical characteristics of the preparation must be determined to

permit a decision to be made as to its acceptability. If tests have to be

performed, they must be done at temperatures compatible with

survival of the micro-organism.

2.7.1.

Wettability

The wettability of solid preparations which are diluted for use (e.g.

wettable powders and water dispersible granules), must be determined

and reported according to CIPAC Method MT 53.3.

2.7.2.

Persistent foaming

The persistence of foaming of preparations to be diluted with water,

must be determined and reported according to CIPAC Method MT 47.

2.7.3.

Suspensibility and suspension stability

—The suspensibility of water dispersible products (e.g. wettable

powders, water dispersible granules, suspension concentrates)

must be determined and reported according to CIPAC Method MT

15, MT 161 or MT 168 as appropriate.

—The spontaneity of dispersion of water dispersible products (e.g.

suspension concentrates and water dispersible granules) must be

determined and reported according to CIPAC Methods MT 160 or

MT 174 as appropriate.

2.7.4.

Dry sieve test and wet sieve test

In order to ensure that dustable powders have a suitable particle size

distribution for ease of application, a dry sieve test must be conducted

and reported according to CIPAC Method MT 59.1.

In the case of water dispersible products, a wet sieve test must be

conducted and reported according to CIPAC Method MT 59.3 or MT

167 as appropriate.

2.7.5.

Particle size distribution (dustable and wettable powders, granules),

content of dust/fines (granules), attrition and friability (granules)

(i) The size distribution of particles in the case of powders, must be

determined and reported according to OECD Method 110.

The nominal size range of granules for direct application must be

determined and reported in accordance with CIPAC MT 58.3, for

water dispersible granules in accordance with CIPAC MT 170.

(ii) The dust content of granular preparations, must be determined

and reported according to CIPAC Method MT 171. If relevant for

operator exposure the particle size of dust must be determined

and reported according to OECD Method 110.

(iii) The friability and attrition characteristics of granules, must be

determined and reported once internationally agreed methods are

available. Where already data are available they must be reported

together with the method used.

2.7.6.

Emulsifiability, re-emulsifiability, emulsion stability

(i) The emulsifiability, emulsion stability and re-emulsifiability of

preparations which form emulsions, must be determined and

reported according to CIPAC Method MT 36 or MT 173 as

appropriate.

(ii) The stability of dilute emulsions and of preparations which are

emulsions, must be determined and reported according to CIPAC

Method MT 20 or MT 173.

2.7.7.

Flowability, pourability (rinsability) and dustability

(i) The flowability of granular preparations must be determined and

reported according to CIPAC Method MT 172.

(ii) The pourability (including rinsed residue) of suspensions (e.g.

suspension concentrates, suspo-emulsions), must be determined

and reported according to CIPAC Method MT 148.

(iii) The dustability of dustable powders must be determined and

reported according to CIPAC Method MT 34 or another suitable

method.

2.8.

Physical, chemical and biological compatibility with other

products including plant protection products with which its use is

to be authorised

2.8.1.

Physical compatibility

The physical compatibility of recommended tank mixes must be

determined and reported.

2.8.2.

Chemical compatibility

The chemical compatibility of recommended tank mixes must be

determined and reported except where examination of the individual

properties of the preparations would establish beyond reasonable

doubt that there is no possibility of reaction taking place. In such

cases it is sufficient to provide that information as justification for not

practically determining the chemical compatibility.

2.8.3.

Biological compatibility

The biological compatibility of tank mixes must be determined and

reported. Effects (e.g. antagonism, fungicidal effects) on the activity

of the micro-organism after mixing with other micro-organisms or

chemicals must be described. The possible interaction of the plant

protection product with other chemical products to be applied on the

crops under the expected condition of use of the preparation should be

investigated, based on the efficacy data. Intervals between application

of the biological pesticide and chemical pesticides should be

specified, if appropriate, in order to avoid loss of efficacy.

2.9.

Adherence and distribution to seeds In the case of preparations for

seed treatment, both distribution and adhesion must be investigated

and reported; in the case of distribution according to CIPAC Method

MT 175.

2.10.

Summary and evaluation of data presented under points 2.1 to 2.9

3. DATA ON APPLICATION

3.1.

Field of use envisaged

The field(s) of use, existing and proposed, for preparations containing

the micro-organism must be specified from among the following

—field use, such as agriculture, horticulture, forestry and viticulture,

—protected crops (e.g. in glasshouses),

—amenity,

—weed control on non-cultivated areas,

—home gardening,

—house plants,

—stored products,

—other (specify).

3.2.

Mode of action

The way by which uptake of the product may occur (e.g. contact,

stomach, inhalation) or the pest controlling action (fungitoxic, fungi-

static action, nutrient competition, etc.) must be stated.

It must also be stated whether or not the product is translocated in

plants and, where relevant, if such translocation is apoplastic,

symplastic or both.

3.3.

Details of intended use

Details of the intended use, e.g. types of harmful organisms controlled

and/or plants or plant products to be protected, must be provided.

Intervals between the application of the plant protection product

containing micro-organisms and chemical pesticides, or a list with

active substances of chemical plant protection products not to be used

together with the plant protection product containing micro-organisms

on the same crop, should also be provided.

3.4.

Application rate

For each method of application and each use, the rate of application

per unit (ha, m 2 ,m 3 ) treated, in terms of g or kg or l for the preparation

and in terms of appropriate units for the micro-organism, must be

provided.

Application rates shall normally be expressed in g or kg/ha or in

kg/m 3 and where appropriate in g or kg/tonne; for protected crops and

home gardening use rates shall be expressed in g or kg/100 m 2 or g or

kg/m 3 .

3.5.

Content of micro-organism in material used (e.g. in the diluted

spray, baits or treated seed)

The content of micro-organism shall be reported, as appropriate, in

number of active unit/ml or g or any other relevant unit.

3.6.

Method of application

The method of application proposed must be described fully, indi-

cating the type of equipment to be used, if any, as well as the type and

volume of diluent to be used per unit of area or volume.

3.7.

Number and timing of applications and duration of protection

The maximum number of applications to be used and their timing,

must be reported. Where relevant the growth stages of the crop or

plants to be protected and the development stages of the harmful

organisms, must be indicated. Where possible and necessary the

interval between applications, in days, must be stated.

The duration of protection afforded both by each application and by

the maximum number of applications to be used, must be indicated.

3.8.

Necessary waiting periods or other precautions to avoid phyto-

pathogenic effects on succeeding crops

Where relevant, minimum waiting periods between last application

and sowing or planting of succeeding crops, which are necessary to

avoid phytopathogenic effects on succeeding crops, must be stated,

and follow from the data provided under section 6, point 6.6.

Limitations on choice of succeeding crops, if any, must be stated.

3.9.

Proposed instructions for use The proposed instructions for use of

the preparation, to be printed on labels and leaflets, must be provided.

4. FURTHER INFORMATION ON THE PLANT PROTECTION

PRODUCT

4.1.

Packaging and compatibility of the preparation with proposed

packaging materials

(i) Packaging to be used must be fully described and specified in

terms of the materials used, manner of construction (e.g. extruded,

welded, etc.), size and capacity, size of opening, type of closure

and seals. It must be designed in accordance with the criteria and

guidelines specified in the FAO‘Guidelines for the Packaging of

Pesticides’.

(ii) The suitability of the packaging, including closures, in terms of its

strength, leakproofness and resistance to normal transport and

handling, must be determined and reported according to ADR

methods 3552, 3553, 3560, 3554, 3555, 3556, 3558, or appro-

priate ADR Methods for intermediate bulk containers, and, where

for the preparation child-resistant closures are required, according

to ISO standard 8317.

(iii) The resistance of the packaging material to its contents must be

reported according to GIFAP Monograph No 17.

4.2.

Procedures for cleaning application equipment Cleaning

procedures for both application equipment and protective clothing

must be described in detail. The effectiveness of the cleaning

procedure must be determined, using e.g. biotests, and reported.

4.3.

Re-entry periods, necessary waiting periods or other precautions

to protect man, livestock and the environment

The information provided must follow from and be supported by the

data provided for the micro-organism(s) and that provided under

sections 7 and 8.

(i) Where relevant pre-harvest intervals, re-entry periods or with-

holding periods necessary to minimise the presence of residues in

or on crops, plants and plant products, or in treated areas or

spaces, with a view to protecting man or livestock, must be

specified e.g.

—pre-harvest interval (in days) for each relevant crop,

—re-entry period (in days) for livestock, to areas to be grazed,

—re-entry period (in hours or days) for man to crops, buildings or

spaces treated,

—withholding period (in days) for animal feedingstuffs,

—waiting period (in days), between application and handling

treated products.

(ii) Where necessary, in the light of the test results, information on

any specific agricultural, plant health or environmental conditions

under which the preparation shall or shall not be used must be

provided.

4.4.

Recommended methods and precautions concerning: handling,

storage, transport or fire

The recommended methods and precautions concerning handling

procedures (detailed) for the storage, at both warehouse and user level

of plant protection products, for their transport and in the event of fire

must be provided. Where relevant, information on combustion

products must be provided. The risks likely to arise and the methods

and procedures to minimise the hazards arising, must be specified.

Procedures to preclude or minimise the generation of waste or

leftovers must be provided.

Where relevant, assessment has to be done according to ISO TR 9122.

The nature and characteristics of protective clothing and equipment

proposed must be provided. The data provided must be sufficient to

evaluate the suitability and effectiveness under realistic conditions of

use (e.g. field or glasshouse circumstances).

4.5.

Measures in the case of an accident

Whether arising during transport, storage or use, detailed procedures

to be followed in the event of an accident, must be provided and

include

—containment of spillages,

—decontamination of areas, vehicles and buildings,

—disposal of damaged packaging, adsorbents and other materials,

—protection of emergency workers and bystanders,

—first aid measures.

4.6.

Procedures for destruction or decontamination of the plant

protection product and its packaging

Procedures for destruction and decontamination must be developed

for both small quantities (user level) and large quantities (warehouse

level). The procedures must be consistent with provisions in place

relating to the disposal of waste and of toxic waste. The means of

disposal proposed should be without unacceptable influence on the

environment and be the most cost effective and practical means of

disposal feasible.

4.6.1.

Controlled incineration

In many cases the preferred or sole means to safely dispose of plant

protection products and in particular the formulants contained in it,

contaminated materials, or contaminated packaging, is through

controlled incineration in a licensed incinerator.

The applicant must provide detailed instructions for safe disposal.

4.6.2.

Others

Other methods to dispose of plant protection products, packaging and

contaminated materials, where proposed, must be fully described.

Data must be provided for such methods, to establish their

effectiveness and safety.

5. ANALYTICAL METHODS

Introduction

The provisions of this section only cover analytical methods required

for post-registration control and monitoring purposes.

It is desirable to have a plant protection product without

contaminants, if possible. The level of acceptable contaminants

should be judged from a risk assessment point of view, by the

director.

Both production and product must be subject to a continuous quality

control by the applicant. The quality criteria for the product should be

submitted.

For analytical methods used for generation of data as required in this

Legal Notice or for other purposes the applicant has to provide a

justifi-cation for the method used; where necessary separate guidance

will be developed for such methods on the basis of the same

requirements as defined for methods for post-registration control and

monitoring purposes.

Descriptions of methods must be provided and include details of

equipment, materials and conditions used. The applicability of

existing CIPAC methods must be reported.

As far as practicable these methods must employ the simplest

approach, involve the minimum cost, and require commonly available

equipment.

For this section the following applies

Impurities

Any component (including contami-

nating

micro-organisms

and/or

chemical substances) other than the

specified micro-organism, originating

from the manufacturing process or from

degradation during storage

Relevant impurities

Impurities, as defined above, that are of

concern for human or animal health

and/or the environment

Metabolites

Metabolites include products resulting

from degradative and biosynthetic

reactions taking place within the micro-

organism or other organisms used to

produce the micro-organism of interest

Relevant metabolites

Metabolites that are of concern for

human or animal health and/or the en-

vironment

Residues

Viable micro-organisms and substances

produced in significant quantities by

these micro-organisms which persist

after the disappearance of the micro-

organisms and are of concern for human

or animal health and/or the en-

vironment.

On request the following samples must be provided

(i) samples of the preparation;

(ii) samples of the micro-organism as manufactured;

(iii) analytical standards of the pure micro-organism;

(iv) analytical standards of relevant metabolites and all other

components included in the residue definition;

(v) if available, samples of reference substances for the relevant impu-

rities.

5.1.

Methods for the analysis of the preparation

—Methods, which must be described in full, must be provided for the

identification and the determination of the content of the micro-

organism in the preparation. In the case of a preparation containing

more than one micro-organism, methods capable of identifying

and determining the content of each one should be provided.

—Methods to establish regular control of the final product

(preparation) in order to show that it does not contain other

organisms than the indicated ones and to establish its uniformity.

—Methods to identify any contaminating micro-organisms of the

preparation.

—Methods used to determine the storage stability and shelf life of the

preparation must be provided.

5.2.

Methods to determine and quantify residues Analytical methods

for the determination of residues, as defined in

Schedule II, Part B, section 4, point 4.2, must be submitted unless it is

justified that the information already submitted according to the

requirements of Schedule II, Part B, section 4, point 4.2, is sufficient.

6. EFFICACY DATA

The provisions for efficacy data have already been adopted under

Commission Directive 93/71/EEC.

7. EFFECTS ON HUMAN HEALTH

For proper evaluation of the toxicity including potential for patho-

genicity and infectiveness of preparations sufficient information

should be available on acute toxicity, irritation and sensitisation of the

micro-organism. If possible, additional information on mode of toxic

action, toxicological profile and all other known toxicological aspects

of the micro-organism should be submitted. Special attention should

be given to co-formulants.

While performing toxicology studies, all signs of infection or patho-

genicity should be noted. Toxicology studies should include clearance

studies.

In the context of the influence that impurities and other components

can have on toxicological behaviour, it is essential that for each study

submitted, a detailed description (specification) of the material used,

be provided. Tests must be conducted using the plant protection

product to be authorised. In particular, it must be clear that the micro-

organism used in the preparation, and the conditions of culturing it,

are the same for which information and data are submitted in the

context of Schedule II, Part B.

A tiered testing system will be applied to the study of the plant

protection product.

7.1.

Basic acute toxicity studies

The studies, data and information to be provided and evaluated, must

be sufficient to permit the identification of effects following a single

exposure to the plant protection product, and in particular to establish,

or indicate

—the toxicity of the plant protection product,

—toxicity of the plant protection product relative to the micro-

organism,

—the time course and characteristics of the effect with full details of

behavioural changes and possible gross pathological findings at

post-mortem,

—where possible the mode of toxic action, and

—the relative hazard associated with the different routes of exposure.

While the emphasis must be on estimating the toxicity ranges

involved, the information generated must also permit the plant

protection product to be classified in accordance with Directive

99/45/EEC. The information generated through acute toxicity testing

is of particular value in assessing hazards likely to arise in accident

situations.

7.1.1.

Acute oral toxicity

Circumstances in which required

An acute oral test should always be carried out unless the applicant

can justify to the satisfaction of the director that Article 3(2) of

Directive 99/45/EEC can be invoked.

Test guideline

The test must be carried out in accordance with Method B.1 or B.1bis

of Commission Directive 92/69/EEC.

7.1.2.

Acute inhalation toxicity

Aim of the test

The test will provide the inhalation toxicity to rats of the plant

protection product.

Circumstances in which required

The test must be carried out where the plant protection product

—is used with fogging equipment,

—is an aerosol,

—is a powder containing a significant proportion of particles of

diameter < 50 micrometre (> 1 % on a weight basis),

—is to be applied from aircraft in cases where inhalation exposure

is relevant,

—is to be applied in a manner which generates a significant

proportion of particles or droplets of diameter < 50 micrometre

(> 1 % on a weight basis),

—contains a volatile component at greater than 10 %.

Test guideline

The test must be carried out in accordance with Method B.2 of

Directive 92/69/EEC.

7.1.3.

Acute percutaneous toxicity

Circumstances in which required

An acute percutaneous test should always be carried out unless the

applicant can justify to the satisfaction of the director that Directive

99/45/EEC can be invoked.

Test guideline

The test must be carried out in accordance with Method B.3 of

Directive 92/69/EEC.

7.2.

Additional acute toxicity studies

7.2.1.

Skin irritation

Aim of the test

The test will provide the potential of skin irritancy of the plant

protection product including the potential reversibility of the effects

observed.

Circumstances in which required

The skin irritancy of the plant protection product must always be

determined, except where the formulants are not expected to be skin

irritant or the micro-organism is shown not to be skin irritant or where

it is likely, as indicated in the test guideline, that severe skin effects

can be excluded.

Test guideline

The test must be carried out in accordance with Method B.4 of

Directive 92/69/EEC.

7.2.2.

Eye irritation

Aim of the test

The test will provide the potential for eye irritation of the plant

protection product, including the potential reversibility of the effects

observed.

Circumstances in which required

The eye irritancy of the plant protection product must be determined,

where the formulants are suspected to be eye irritant, except where the

micro-organism is eye irritant or where it is likely, as indicated in the

test guideline, that severe effects on the eyes may be produced.

Test guideline

The eye irritation must be determined in accordance with Method B.5

of Directive 92/69/EEC.

7.2.3.

Skin sensitisation

Aim of the test

The test will provide sufficient information to assess the potential of

the plant protection product to provoke skin sensitisation reactions.

Circumstances in which required

The test must be carried out where the formulants are suspected to

have skin sensitising properties, except where the micro-organism(s)

or the formulants are known to have skin sensitising properties.

Test guideline

The tests have to be carried out in accordance with Method B.6 of

Directive 92/69/EEC.

7.3.

Data on exposure

The risks for those in contact with plant protection products

(operators, bystanders, workers), depend on the physical, chemical

and toxico-logical properties of the plant protection product as well as

the type of the product (undiluted/diluted), formulation type, and on

the route, the degree and duration of exposure. Sufficient information

and data must be generated and reported to permit an assessment of

the extent of exposure to the plant protection product likely to occur

under the proposed conditions of use.

In the cases where there is particular concern on the possibility of

dermal absorption based on the information for the micro-organism

available in Schedule II, Part B, section 5, or from the information

provided for the preparation in the present section of Schedule III,

Part B, further dermal absorption data can be necessary.

Results from exposure monitoring during production or use of the

product must be submitted.

The abovementioned information and data must provide the basis for

the selection of appropriate protective measures including personal

protective equipment to be used by operators and workers and to be

specified on the label.

7.4.

Available toxicological data relating to non-active substances A

copy of the notification and the safety data sheet submitted in the

context of European Parliament and Council Directive 1999/45/EC

and Regulation (EC) No 1907/2006 of the European Parliament and

of the Council of 18 December 2006 concerning the Registration,

Evaluation, Authorisation and Restriction of Chemicals (REACH),

establishing a European Chemicals Agency, must be submitted for

each formulant. All other available information should be submitted.

7.5.

Supplementary studies for combinations of plant protection

products

Aim of the test

In certain cases it may be necessary to carry out the studies as referred

to under points 7.1 to 7.2.3 for a combination of plant protection

products where the product label includes requirements for use of the

plant protection product with other plant protection products and/or

with adjuvants as a tank mix. Decisions as to the need for

supplementary studies must be made on a case-by-case basis, taking

into account the results of the acute toxicity studies of the individual

plant protection products, the possibility for exposure to the combi-

nation of the products concerned and available information or

practical experience with the products concerned or similar products.

7.6.

Summary and evaluation of health effects A summary of all data

and information provided under paragraphs 7.1 through 7.5, must be

submitted, and include a detailed and critical assessment of those data

in the context of relevant evaluative and decision-making criteria and

guidelines, with particular reference to the risks for man and animals

that may or do arise, and the extent, quality and reliability of the

database.

8. RESIDUES IN OR ON TREATED PRODUCTS, FOOD AND FEED

The same provisions as detailed in Schedule II, Part B, section 6,

apply; the information required according to this section has to be

provided unless it is possible to extrapolate the residue behaviour of

the plant protection product on the basis of the data available for the

micro-organism. Special attention should be paid towards the

influence of formulation substances on the residue behaviour of the

micro-organism and its metabolites.

9. FATE AND BEHAVIOUR IN THE ENVIRONMENT The same

provisions as detailed in Schedule II, Part B, section 7, apply; the

information required according to this section has to be provided

unless it is possible to extrapolate the fate and behaviour of the plant

protection product in the environment on the basis of the data

available in Schedule II, Part B, section 7.

10. EFFECTS ON NON-TARGET ORGANISMS

Introduction

(i) The information provided, taken together with that for the

micro-organism(s), must be sufficient to permit an assessment

of the impact on non-target species (flora and fauna), of the

plant protection product, when used as proposed. Impact can

result from single, prolonged or repeated exposure, and can be

reversible, or irreversible.

(ii) The choice of the appropriate non-target organisms for testing

of environmental effects should be based on the information on

the micro-organism, as required in Schedule II, Part B, and on

the information on the formulants and other components, as

required by sections 1 to 9 of the present Schedule. From such

knowledge it would be possible to choose the appropriate test

organisms, such as organisms closely related to the target

organism.

(iii) In particular, the information provided for the plant protection

product, together with other relevant information, and that

provided for the micro-organism, should be sufficient to

—specify the hazard symbols, the indications of danger, and

relevant risk and safety phrases for the protection of the

environment, to be mentioned on packaging (containers),

—permit an evaluation of the short- and long-term risks for

non-target species.

—populations, communities, and processes as appropriate,

—permit an evaluation whether special precautions are

necessary for the protection of non-target species.

(iv) There is a need to report all potentially adverse effects found

during routine investigations of environmental effects and to

undertake and report such additional studies which may be

necessary to investigate the mechanisms involved and assess

the significance of these effects.

(v) In general, much of the data relating to impact on non-target

species, required for authorisation of plant protection products,

will have been submitted and evaluated for the inclusion of the

micro-organism(s) in Schedule I.

(vi) Where exposure data are necessary to decide whether a study

has to be performed, the data obtained in accordance with the

provisions of Schedule III, Part B, section 9, should be used.

For the estimation of exposure of organisms all relevant infor-

mation on the plant protection product and on the micro-

organism must be taken into account. Where relevant the para-

meters provided for in this section should be used. Where it

appears from available data that the plant protection product

has a stronger effect than the micro-organism, the data on

effects on non target organisms of the plant protection product

have to be used for the calculation of relevant effec-t/exposure

ratios.

(vii) In order to facilitate the assessment of the significance of test

results obtained, the same strain of each relevant species

should where possible be used in the various specified tests for

effects on non target organisms.

10.1.

Effects on birds

The same information as provided in Schedule II, Part B, section 8,

point 8.1, has to be reported where it is not possible to predict the

effects of the plant protection product on the basis of the data

available for the micro-organism, unless it can be justified that

exposure of birds is unlikely to occur.

10.2.

Effects on aquatic organisms

The same information as provided in Schedule II, Part B, section 8,

point 8.2, has to be reported where it is not possible to predict the

effects of the plant protection product on the basis of the data

available for the micro-organism, unless it can be justified that

exposure of aquatic organisms is unlikely to occur.

10.3.

Effects on bees

The same information as provided in Schedule II, Part B, section 8,

point 8.3, has to be reported where it is not possible to predict the

effects of the plant protection product on the basis of the data

available for the micro-organism, unless it can be justified that

exposure of bees is unlikely to occur.

10.4.

Effects on arthropods other than bees

The same information as provided in Schedule II, Part B, section 8,

point 8.4, has to be reported where it is not possible to predict the

effects of the plant protection product on the basis of the data

available for the micro-organism, unless it can be justified that

exposure of arthropods other than bees is unlikely to occur.

10.5.

Effects on earthworms

The same information as provided in Schedule II, Part B, section 8,

point 8.5, has to be reported where it is not possible to predict the

effects of the plant protection product on the basis of the data

available for the micro-organism, unless it can be justified that

exposure of earthworms is unlikely to occur.

10.6.

Effects on soil micro-organisms

The same information as provided in Schedule II, Part B, section 8,

point 8.6, has to be reported where it is not possible to predict the

effects of the plant protection product on the basis of the data

available for the micro-organism, unless it can be justified that

exposure of non target soil micro-organisms is unlikely to occur.

10.7.

Additional studies

Expert judgement is required to decide whether additional studies are

necessary. Such decision will take into consideration the available

information in this and other sections, in particular data on the speci-

ficity of the micro-organism, and the expected exposure. Useful

information may also be available from the observations carried out

in efficacy testing.

Special attention should be given to possible effects on naturally

occurring and deliberately released organisms of importance in IPM.

In particular the compatibility of the product with IPM should be

taken into consideration.

Additional studies might include further studies on additional species

or higher tier studies such as studies on selected non-target

organisms.

Before performing such studies, the applicant shall seek agreement

of the competent authorities on the type of study to be performed.

11. SUMMARY AND EVALUATION OF ENVIRONMENTAL

IMPACT

A summary and evaluation of all data relevant to the environmental

impact should be carried out according to the guidance given by the

competent authority concerning the format of such summaries and

evaluations. It should include a detailed and critical assessment of

those data in the context of relevant evaluative and decision making

criteria and guidelines, with particular reference to the risks for the

environment and non-target species that may or do arise, and the

extent, quality and reliability of the database. In particular the

following issues should be addressed

—prediction of distribution and fate in the environment, and the time

courses involved,

—identification of non-target species and populations at risk, and

prediction of the extent of potential exposure,

—identification of precautions necessary to avoid or minimise con-

tamination of the environment, and for the protection of non-

target species.

(1) Prodott għall-ħarsien tal-pjanti m’għandux jiġi

awtorizzat kemm-il darba

(a) is-sustanzi attivi tiegħu ma jkunux elenkati fl-

Iskeda I u kull kundizzjoni stabbilita hemm ma tkunx ġiet

sodisfatta, u, fir-rigward tal-punti li ġejjin (b), (ċ), (d) u (e),

skond il-prinċipji uniformi previsti fl-Iskeda VI;

(b) għaldaqstant għar-rigward ta’ paragrafu (a) ta’ dan

ir-regolament ma jiġix stabbilit, fid-dawl tat-tagħrif xjentifiku

u tekniku preżenti, u ma jkunx jidher minn evalwazzjoni tar-

rapport li jipprovdi għalih l-Iskeda III, illi meta jintuża skond

ir-regolament 3 (3), u wara li jiġu kunsidrati l-kundizzjonijiet

kollha normali li taħthom jista’ jintuża, u l-konsegwenzi tal-

użu tiegħu

(i) ikun effettiv biżżejjed;

(ii) ma jkollu ebda effett inaċċettabbli fuq il-

prodotti tal-pjanti;

(iii) ma jkunx jikkawża tbatija u wġigħ bla bżonn

lil vertebrati li jridu jiġi kontrollati;

(iv) ma jkollux effetti dannużi għas-saħħa tal-

bnedmin jew tal-annimali, sew jekk direttament sew

jekk indirettament (eż. permezz ta’ l-ilma tax-xorb, ikel

jew għalf) jew fuq ilma ta’ taħt l-art;

(v) ma jkollu ebda effett inaċċettabbli fuq

l-ambjent, speċjalment fir-rigward ta’ dak li jista’ jseħħ

minnu u d-distribuzzjoni tiegħu fl-ambjent, b’mod

partikolari il-kontaminazzjoni ta’ l-ilma, inkluż l-ilma

tax-xorb u l-ilma ta’ taħt l-art, u l-impatt tiegħu fuq speċi

li l-prodott ma jkunx immirat kontrihom;

(ċ) in-natura u l-kwantità tas-sustanzi attivi u,

fejn xieraq, kull impuritajiet u ko-formulanti ta’ natura

tossikoloġikament jew ekotossikoloġikament sinifikanti

jistgħu jiġu stabbiliti permezz ta’ mezzi addatti;

(d) il-fdalijiet tagħha, li jirriżultaw mill-użu awtorizzat,

u li jkunu ta’ importanza mil-lat tossikoloġiku jew ambjentali,

jistgħu jiġu stabbiliti permezz ta’ metodi addatti li jintużaw

b’mod ġenerali;

(e) il-proprjetajiet fiżiċi u kimiċi tiegħu jkunu ġew

stabbiliti u meqjusa bħala aċċettabbli għall-iskop ta’ l-użu

xieraq u l-ħażna tal-prodott;

(f) meta addatt, l-MRLs għall-prodotti agrikoli

milqutin mill-użu msemmi fl-awtorizzazzjoni ikunu ffissati

jew modifikati skond ir-Regolament (KE) Numru 396/2005.

(2) L-awtorizzazzjoni għandha tistipula r-rekwiżiti li

għandhom x’jaqsmu ma’ l-introduzzjoni fis-suq u l-użu tal-prodott

jew għall-inqas dawk immirati għall-assigurar ta’ konformità mad-

dispożizzjonijiet tar-regolament 4 (1) (b).

(3) Id-direttur għandu jiżgura li l-konformità mar-

rekwiżiti esposti fir-regolament 4 (1) (b) sa (f) tiġi stabbilita minn

testijiet u analiżi uffiċjali jew rikonoxxuti uffiċjalment magħmulin

taħt kondizzjonijiet agrikoli, tas-saħħa tal-pjanti u ambjentali

rilevanti għall-użu tal-prodott għall-ħarsien tal-pjanti konċernat u li

jirrappreżentaw il-kundizzjonijiet li jeżistu fl-inħawi fejn il-prodott

huwa ntiż li se jintuża.

(4) Bla preġudizzju għar-regolament 4 (5) u

r-regolament 4 (6), l-awtorizzazzjonijiet għandhom jingħataw

biss għal perjodu fiss li jestendi biss sa 10 snin, stabbilit mid-

Direttur; dawn jistgħu jiġġeddu wara verifika li l-kundizzjonijiet

imposti fir-regolament 4 (1) għadhom qed jiġu mwettqa. Meta ssir

applikazzjoni għal tiġdid, dan jista’ jingħata għall-perjodu meħtieġ

mid-direttur biex jagħmel l-verifika meħtieġa.

(5) L-awtorizzazzjonijiet jistgħu jiġu riveduti f’kull

żmien jekk ikun hemm indikazzjonijiet li xi wieħed jew aktar

mir-rekwiżiti msemmija fir-regolament 4 (1) ma jkunux għadhom

sodisfatti. F’każijiet bħal dawn, id-Direttur jista’ jitlob lill-

applikant għall-awtorizzazzjoni jew lill-parti li lilha tkun ingħatat

estensjoni tal-qasam ta’ applikazzjoni skond ir-regolament 9

biex tissottometti informazzjoni ulterjuri li tkun meħtieġa għar-

reviżjoni. L-awtorizzazzjoni tista’, fejn ikun meħtieġ, tiġi estiża

għall-perjodu meħtieġ biex titlesta reviżjoni u tingħata l-imsemmija

informazzjoni ulterjuri.

(6) (a) Bla preġudizzju għad-Deċiżjonijiet li jkunu

diġà ttieħdu skond ir-regolament 10, awtorizzazzjoni għandha

tiġi kanċellata jekk jiġi stabbilit li r-rekwiżiti għall-akkwist ta’

awtorizzazzjoni mhumiex sodisfatti jew m’għadhomx sodisfatti,

jew li dettalji foloz jew qarrieqa kienu ngħataw dwar il-fatti li

abbażi tagħhom tkun ingħatat l-awtorizzazzjoni, jew għandha tiġi

modifikata jekk jiġi stabbilit li, fuq il-bażi ta’ żviluppi fit-tagħrif

xjentifiku u tekniku, il-mod ta’ l-użu u l-ammonti użati jistgħu jiġu

modifikati.

(b) Awtorizzazjoni tista’ wkoll tiġi kanċellata jew

modifikata fuq talba tad-detentur ta’ l-awtorizzazzjoni, li għandu

jagħti r-raġunijiet għala. L-emendi jitsgħu jingħataw biss jekk jiġi

stabbilit li r-rekwiżiti tar-regolament 4 (1) ikunu għadhom qegħdin

jiġu mwettqa.

(ċ) Meta awtorizzazzjoni tiġi rtirata mid-Direttur,

id-detentur ta’ l-awtorizzazzjoni għandu minnufih jiġi infurmat

bil-miktub bir-raġunijiet dettaljati li fuqhom id-deċiżjoni kienet

ibbażata u d-Direttur għandu jippubblika dan l-irtirar b’avviż fil-

Gazzetta. Barra dan, id-Direttur jista’ jagħti perjodu ta’ grazzja

għar-rimi, ħżin, introduzzjoni fis-suq u l-użu ta’ ħażniet eżistenti,

li jdum skond ir-raġuni tal-irtirar, mingħajr preġudizzju għal kull

perjodu mogħti fid-deċiżjoni meħudha taħt ir-regolamenti 22

and 24 ta’ dawn ir-regolamenti, jew ir-regolament 6 (1) jew ir-

regolament 8 (1) jew (2) ta’ dawn ir-regolamenti.

(7) Bla preġudizzju għal kull dispożizzjoni oħra

magħmula minn jew taħt dan l-Att, għandu jkun id-dmir ta’ kull

persuna li jkollha fil-pussess tagħha awtorizzazzjoni mogħtija lilha

skond dawn ir-regolamenti li

(a) tinforma lid-Direttur bil-miktub, kemm jista’ jkun

malajr, b’kull bidla f’xi informazzjoni mogħtija lid-Direttur

għall-għoti ta’ awtorizzazzjoni;

(b) tinforma lid-Direttur, kemm jista’ jkun malajr,

b’kull effett ħażin mhux mistenni fuq l-ambjent jew fuq

l-ekosistema b’riżultat ta’ l-użu, tixrid, skartar, rimi jew mod

ieħor tal-prodott għall-ħarsien tal-pjanti;

(ċ) tinforma lid-Direttur, kemm jista’ jkun malajr,

b’kull effett ħażin mhux mistenni fuq xi persuna umana jew

annimal li jikkunsmaw xi pjanta jew prodott minn pjanta li

għandu fdalijiet li għandhom x’jaqsmu mal-prodott għall-

ħarsien tal-pjanti;

(d) tippermetti lid-Direttur jew lir-rappreżentant

awtorizzat tiegħu aċċess għall-art jew bini f ’kull ħin

raġjonevoli;

(e) tikkonforma ma’ kull dispożizzjoni magħmula

minn jew taħt l-Att.

STANDARD PHRASES FOR SPECIAL RISKS FOR HUMANS OR THE

ENVIRONMENT AS REFERRED TO IN REGULATION 16

INTRODUCTION

The following additional standard phrases are defined to supplement the phrases

provided for by Directive 1999/45/EC, which applies to plant-protection

products. The provisions of that Directive shall also be used for plant-protection

products containing micro-organisms or viruses as active substances. The

labelling of products containing these active substances shall also reflect the

provisions concerning dermal and respiratory sensitisation testing, which are

laid down in Annex IIb and Annex IIIb to Directive 91/414/EEC.

The harmonised phrases provide the basis for complementary and specific

instructions for use and are, therefore, without prejudice to other elements of

regulation 16, in particular regulation 16(1)(k) to (n) and 16(4).

1. Standard phrases for special risks

1.1.Special risks related to humans (RSh)

RSh 1

BG

Токсичен при контакт с очите.

ES

Tóxico en contacto con los ojos.

CS

Toxický při styku s očima.

DA

Giftig ved kontakt med øjnene.

DE

Giftig bei Kontakt mit den Augen.

ET

Mürgine silma sattumisel.

EL

Τοξικό όταν έρθει σε επαφή µε τα µάτια.

EN

Toxic by eye contact.

FR

Toxique par contact oculaire.

IT

Tossico per contatto oculare.

LV

Toksisks nonākot saskarē ar acīm.

LT

Toksiška patekus į akis.

HU

Szemmel érintkezve mérgezo.

MT

Tossiku meta jmiss ma' l-għajnejn.

NL

Giftig bij oogcontact.

PL

Dziala toksycznie w kontakcie z oczami.

PT

Tóxico por contacto com os olhos.

RO

Toxic în contact cu ochii!

SK

Jedovatý pri kontakte s očami.

SL

Strupeno v stiku z ocmi.

FI

Myrkyllistä joutuessaan silmään.

SV

Giftigt vid kontakt med ögonen.

RSh 2

BG

Може да причини фотосенсибилизация.

ES

Puede causar fotosensibilización.

CS

Může vyvolat fotosenzibilizaci

DA

Kan give overfølsomhed over for sollys/UV-stråling.

DE

Sensibilisierung durch Licht möglich.

ET

Võib põhjustada valgussensibiliseerimist.

EL

Μπορεί να προκαλέσει φωτοευαισθητοποίηση.

EN

May cause photosensitisation.

FR

Peut entraîner une photosensibilisation.

IT

Può causare fotosensibilizzazione.

LV

Var izraisit fotosensibilizaciju.

LT

Gali sukelti fotosensibilizaciją.

HU

Fényérzékenységet okozhat .

MT

Jista' jikkawża fotosensitizzazzjoni.

NL

Kan fotosensibilisatie veroorzaken.

PL

Może powodować nadwrażliwość na światło.

PT

Pode causar fotossensibilização.

RO

Poate cauza fotosensibilitate!

SK

Môže spôsobiť fotosenzibilizáciu .

SL

Lahko povzroči preobčutljivost na svetlobo.

FI

Voi aiheuttaa herkistymistä valolle.

SV

Kan orsaka överkänslighet för solljus/UV-strålning.

RSh 3

BG

Контактът с парите причинява изгаряния на кожата и

очите, контактът с течността причинява измръзвания.

ES

El contacto con los vapores provoca quemaduras de la piel y

de los ojos; el contacto con el producto líquido provoca

conge-lación.

CS

Při styku s parami způsobuje poleptání kůže a očí a při styku

s kapalinou způsobuje omrzliny

DA

Kontakt med dampe giver ætsninger på hud og øjne, og

kontakt med væske giver forfrysninger.

DE

Kontakt mit Dämpfen verursacht Verätzungen an Haut und

Augen und Kontakt mit der Flüssigkeit verursacht

Erfrierungen.

ET

Kokkupuude auruga põhjustab põletushaavu nahale ja

silmadele ning kokkupuude vedelikuga põhjustab külmumist.

EL

Οι ατµοί µπορεί να προκαλέσουν εγκαύµατα στο δέρµα και

στα µάτια·η επαφή µε το υγρό µπορεί να προκαλέσει κρυο-

παγήµατα.

EN

Contact with vapour causes burns to skin and eyes and

contact with liquid causes freezing.

FR

Le contact avec les vapeurs peut provoquer des brûlures de la

peau et des yeux; le contact avec le gaz liquide peut causer

des engelures.

IT

Il contatto con il vapore può causare ustioni della pelle e

bruciori agli occhi; il contatto con il liquido può causare

congelamento.

LV

Saskare ar tvaikiem izraisa ādas un acu apdegumus un

saskare ar šķidrumu izraisa apsaldējumus

LT

Garai sukelia odos ir akių nudegimą, skystis- nušalimą.

HU

Az anyag gőzével való érintkezés a bőr és a szem égési

sérülését okozhatja, illetve a folyadékkal való érintkezés

fagyást okozhat.

MT

Kuntatt mal-fwar jikkawza ħruq fil-ġilda u fl-għajnejn filwaqt

li kuntatt mal-likwidu jikkawża iffrizar.

NL

Contact met de damp veroorzaakt brandwonden aan huid en

ogen; contact met de vloeistof veroorzaakt bevriezing.

PL

Kontakt z oparami powoduje poparzenia skóry i oczu,

kontakt z cieczą powoduje zamarzanie.

PT

O contacto com vapores do produto provoca queimaduras na

pele e nos olhos; o contacto com o produto líquido provoca

congelação.

RO

Contactul cu vaporii cauzează arsuri ale pielii

i ochilor, iar

contactul cu lichidul cauzează degerături!

SK

Pri kontakte s parou spôsobuje popáleniny pokožky a očí a

kontakt s kvapalinou spôsobuje omrzliny.

SL

Stik s hlapi povzroča opekline kože in oči, stik s tekočino

povzroča ozebline.

FI

Kosketus höyryyn voi aiheuttaa palovammoja iholle ja silmiin

ja kosketus nesteeseen paleltumavammoja.

SV

Kontakt med ångor orsakar frätskador på hud och ögon,

kontakt med vätska orsakar förfrysningsskador.

1.2.

Special risks related to the environment (RSe)

None.

2. Attribution criteria for standard phrases for special risks

2.1.

Attribution criteria for standard phrases related to humans

RSh 1

Toxic by eye contact.

The phrase shall be assigned where an eye irritation test according to

Schedule IIIA point 7.1.5 has resulted in overt signs of systemic toxicity

(e.g. related to cholinesterase inhibition) or mortality among the animals

tested, which is likely to be attributable to absorption of the active

substance through the mucous membranes of the eye. The risk phrase

shall also be applied if there is evidence in humans for systemic toxicity

after eye contact.

Eye protection should be specified in these cases, as outlined in the

general provisions of Schedule V.

RSh 2

May cause photosensitisation.

The phrase shall be assigned where there is clear evidence from experi-

mental systems or documented human exposure that products show

photosensitising effects. The phrase shall also be applied to products

containing a given active substance or formulation ingredient, which

shows photosensitising effects in humans if the product contains this

photosensitising component at a concentration of 1 % (w/w) or higher.

Personal protective measures should be specified in these cases, as

outlined in the general provisions of Schedule V.

RSh 3

Contact with vapour causes burns to skin and eyes and contact with liquid

causes freezing.

The phrase shall be assigned to plant-protection products being

formulated as liquefied gas, where appropriate (e.g. preparations of

methyl bromide).

Personal protective measures should be specified in these cases, as

outlined in the general provisions of Schedule V.

In cases where R34 or 35 are applied according to Directive 1999/45/EC,

the phrase shall not be used.

2.2.

Attribution criteria for standard phrases related to the environment

None.