S.I. No. 200/1995 - European Communities (Authorization, Placing on The Market, Use and Control of Plant Protection Products) (Amendment) Regulations, 1995.

1.1.

Include a technical dossier supplying the information necessary for evaluating 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 referred to or described in this Annex, in the case of studies initiated before the adoption of the modification of this Annex, the information shall be generated using suitable internationally or nationally validated test guidelines or, in the absence thereof, test guidelines accepted by the competent authority;

1.3

in the event of a test guideline being inappropriate or not described, or where another one than those referred to in this annex has been used, include a justification, which is acceptable to the competent authority for the guideline used;

1.4

include, when required by the competent authority, a full description of test guidelines used, except if they are referred to or described in this Annex, and a full description of any deviations from them including a justification, which is acceptable to the competent authority, 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 competent authority 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/EEC⁷, of 24 November 1986, on the approximation of laws, regulations and administrative provisions of the Member States regarding the protection of animals used for experimental and other scientific purposes.

2.1

Tests and analyses must be conducted in accordance with the principles laid down in Directive 87/18/EEC⁸ of 18 December 1986, on the harmonization of laws, regulations and administrative provisions relating to the application of the principles of good laboratory practice and the verification of their application for tests on chemical substances, 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

Notwithstanding the provisions of point 2.1, during the period to 31 December 1999, tests and analyses done to obtain data on the properties and/or safety with respect to honeybees and beneficial arthropods other than bees may have been conducted by officially recognized testing facilities or organisations, in accordance with the principles laid down in the Sixth Schedule, or in compliance with Irish/European Standard IS/EN 45001, where they are conducted within the territory of the state, and in accordance with the requirements of points 2.2 and 2.3 of the introduction to Annex III to Directive 93/71/EEC, where they are conducted outside the territory of the state.

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 representative in the territory of the State, 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 substance in Annex I, there are changes in the location or number of manufacturers, the information required must again be notified to the Commission and the Member States.

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. Additionally 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 substances and other than impurities resulting from the manufacturing process, the function of the component (additive) must be given—

antifoaming agent

buffer

antifreeze

dispersing agent

binder

stabiliser

other (specify)

1.11

Analytical profile of batches

Representative samples of the active substance must be analyzed 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 analyzed. The actual content of components which are particularly undesirable because of their toxicological, 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 substances

( i ) The information provided, must describe the physical and chemical properties of active substances and together with other relevant information, must serve to characterize them. In particular, the information provided must permit—

— 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 on 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 no need to investigate and report all potentially adverse effects found during routine toxicological investigations (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 provided.

(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 radio labelled 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 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 Annex 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 those 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 metabolism 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 route of administration of the test substance depends on the main exposure routes. In cases where exposure is mainly to 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 animals

Quite limited data, as described below and restricted to one test species (normally the rat) may be all that is required. These data can provide information useful in the design and interpretation of subsequent toxicity tests. However, it must be remembered that information on inter species 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 of 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 investigated.

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 88/302/EEC¹⁰, 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 changes at postmortem,

— 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 the Directive of 1967. 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 EEC 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 EEC Method B 3.

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 a liquified gas,

— to be used as a fumigant,

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

— to be used with fogging equipment,

— has a vapour pressure> 1 x 10^-2 Pa and is to be included in preparations to be used in enclosed spaces such as warehouses or glasshouses,

— to be included in preparations which are powders containing a significant proportion of particles of diameter1% on a weight basis), or

— to be included in preparations to be applied in a manner which generates a significant proportion of particles or droplets of diameter1% on a weight basis).

Test Guideline

The test must be carried out in accordance with EEC Method B 2.

5.2.4

Skin irritation

Aim of the test

The test will provide information as to the potential for 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 and reported 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 EEC Method B 4.

5.2.5

Eye irritation

Aim of the test

The test will provide information as to the potential for eye irritancy of the active substance, including the potential reversibility of the effects observed.

Circumstances in which required

Eye irritation tests must be conducted and reported except where it is likely, as indicated in the test guideline, that severe effects on the eye may be produced.

Test Guideline

The test must be carried out in accordance with EEC Method B 5.

5.2.6

Skin sensitization

Aim of the 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 EEC Method B 6.

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 effects of the active substance and the risks to workers who may be exposed over extensive periods. In addition short-term studies provide information which is useful in the design on 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,

— the toxicity of the active substance including where possible the NOAEL,

— the 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 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 can 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 EEC Method B 7.

5.3.2

Oral 90-day study

Circumstances in which required

The short-term (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 Guideline

Commission Directive 88/3O2/EEC¹⁰, Part B, sub-chronic oral toxicity test.

5.3.3

Other routes

Circumstances in which required

For the assessment of the significance of operator exposure, percutaneous studies may be useful.

For volatile substances (vapour pressure> 10^-2 Pa) expert judgement is required to decide whether the short-term studies have to be performed by the oral inhalation route of exposure.

Test Guidelines

— 28-day dermal: EEC Method B 9,

— 90-day dermal: Commission Directive 88/302/EEC¹⁰, Part B, sub-chronic dermal toxicity study,

— 28-day inhalation: EEC Method B 8,

— 90-day inhalation; Commission Directive 88/3O2/EEC¹⁰,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, and

— 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 dependent upon the interpretation of results obtained 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 reported.

Test Guidelines

Acceptable test guidelines are—

EEC Method B 14 — Salmonella Typhimurium reverse mutation assay,

EEC Method B 10—in vitro mammalian cytogenetic test, Commission Directive 88/302/EEC¹⁰, 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 testing must be done, taking into consideration all 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 for that/those previously used.

If the in vitro cytogenetic test is positive, an in vitro test using somatic cells (metaphase analysis in rodent bone marrow or micronucleus 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—

EEC Method B 12 — micronucleus test, Commission Directive 88/302/EEC¹⁰, Part B — mouse spot test,

EEC Method B 11—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 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 information regarding toxicokinetics, use and anticipated exposure. Suitable tests involve interaction with DNA (such as the dominant lethal assay), to assess the potential for inherited effects and possibly to make a quantifiable assessment of heritable effects. It is recognized that in view of their complexity, the use of quantitative studies requires 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 with the active substance, using the mouse as test species, must be conducted.

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. Historical control data provided must include—

— the identification of species and strain, the name of the supplier and the specific colony identification, if the supplier has more than one geographical location,

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

— a description of the general conditions under which animals were maintained, including the type or brand of diet and, where possible, the amount consumed,

— the approximate age, in days, of the control animals at the beginning of the study and at the time of killing or death,

— a description of the control group mortality pattern observed during or at the end of the study, and other pertinent observations (e.g. diseases, infections),

— the names of the laboratory and of the examining scientists responsible for gathering and interpreting 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 metabolism and toxicokinetic data. The highest dose in the carcinogenicity study should elicit signs of minimal toxicity such as slight depression in body-weight (less than 10%), without causing tissue necrosis or metabolic saturation and without substantially altering the 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, unassociated tumours, whether benign or malignant, occurring in the same organ must not be combined, for reporting purposes. In the interests of avoiding confusion, terminology such as that developed by the American Society of Toxicologic Pathologists¹¹, 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 the mechanism of action and available, special histological staining) techniques, histochemical techniques and electron microscope examinations, must be conducted and reported.

Test Guideline

Commission Directive 88/3O2/EEC¹⁰,Part B, chronic toxicity test, carcinogenicity test or combined chronic toxicity/carcinogenicity test.

5.6

Reproductive toxicity

Adverse reproductive effects are of two main types—

— impairment of male or female fertility, and

— effects 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 unnecessary, that claim must be fully justified.

While the standard reference points 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. Historical control data provided must include—

— the identification of species and strain, the name of the supplier and the specific colony identification, if the supplier has more than one geographical location,

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

— a description of the general conditions under which animals were maintained, including the type of brand of diet and, where possible, the amount consumed,

— the approximate age, in days, of the control animals at the beginning of the study and at the time of killing or death,

— a 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

— the names and the laboratory and of the examining scientists responsible for gathering and interpreting pathological 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 on 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 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

Commission Directive 88/302/EEC¹⁰, 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 effects on reproduction and as far as this information is not yet available it could be necessary to perform supplementary studies and information—

— separate male and female studies,

— three segment design studies,

— 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 in pregnant animals.

Circumstances in which required

The tests must always be carried out.

Test guideline

Commission Directive 88/302/EEC¹⁰,Part B, teratogenicity test — rodent and non-rodent.

5.7

Delayed neurotoxicity studies

Aim of the test

The test will provide sufficient data to establish if the active substance could provoke delayed neurotoxicity after exposure.

Circumstances in which required

These studies must be carried out for substances of similar or related structures to those known to have been capable of inducing delayed neurotoxicity, such as organophosphates.

Test Guideline

The test must be carried out in accordance with OECD Guideline 418.

5.8

Other toxicological studies

5.8.1

Toxicity studies with 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 may be necessary to carry out supplementary studies to further clarify the nature of observed effects. Such studies could include—

— studies on absorption, distribution, excretion and metabolism,

— studies on neurotoxic potential,

— studies on immunotoxicological potential,

— studies using 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 Article 5 of Council Directive 80/1107/EEC¹², on the protection of workers from the risks related to exposure to chemical, physical and biological agents at work, practical data and information relevant to the recognition of the symptoms of poisoning, and on the effectiveness of first aid and therapeutic measures must be submitted. Specific references to the investigations relative to 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

Medical surveillance on manufacturing plant personnel

Reports of occupational health surveillance programmes, supported with detailed information on the design of the programmes, on exposure to the active substance and exposure to other chemicals, must be submitted. Such reports should, where feasible, 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, the 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 documentation can be of particular value, in confirming the validity of extrapolations from animals 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 epidemiological studies if appropriate

Where available, and supported with data on levels and duration of exposure, and where conducted in accordance with recognized standards¹³, epidemiological studies are of particular value and must be submitted.

5.9.4

Diagnosis of poisoning (determination of active substance, metabolites), specific signs of poisoning, clinical tests

A detailed description of the clinical signs 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 reported.

Therapeutic regimes for use in the event of poisoning or contamination 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 a description of the impact of—

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

— varying time periods between exposure, or ingestion, and commencement of treatment.

5.11

Summary of mammalian toxicology and overall conclusions

A summary of all information provided in accordance with paragraphs 5.1 through 5.9 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.

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 (paragraph 5 (iv)), the relevance of the data as submitted, to 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 estimation of the ADI and AOEL(s) for the active substance must be submitted.

6

Residues in or on treated products, food and feed

6.1

Identification of breakdown and reaction products and of metabolites in treated plants or products

6.2

Behaviour of residue of the active substance and its metabolites from the time of application until harvest or out-loading of stored products — uptake and distribution in, and where relevant on, plants, kinetics of disappearance, binding to plant constituents, etc.

6.3

Overall material balance for the active substance. Sufficient residue data from supervised trials to demonstrate that residues likely to arise from the proposed treatments would not be or concern for human and animal health

6.4

Estimation of the potential and actual exposure through diet and other means, such as residue monitoring data for products in the distribution chain, or such as data concerning exposure via air, water, etc.

6.5

Feeding and metabolism studies in livestock (if residues remain in or on crops or parts of crops used for feed) to permit evaluation of residues in foodstuffs of animal origin

6.6

Effects of industrial processing and/or household preparation on the nature and magnitude of residues

6.7

Summary and evaluation of residue behaviour resulting from data submitted pursuant to points 6.1 to 6.6

7

Fate and behaviour in the environment

Introduction

(i) The introduction provided, taken together with that for one or more preparations containing the active substance, must be sufficient to permit 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 Annex I;

— specify appropriate conditions or restrictions to be associated with any inclusion in Annex 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 environment, which are to be included on packaging (containers);

— predict the distribution, fate, and behaviour in the environment of the active substance and relevant metabolites, degradation and reaction products 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) 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 manufacture of preparations to be authorized except where radiolabelled 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 radiolabelled test material is used, radiolabels should be positioned at sites (one or more as necessary), to facilitate elucidation of metabolic and degradative pathways and to facilitate investigation of the distribution of the active substance and of its metabolites, reaction and degradation products in the environment.

(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 must be taken into account.

(vi) Where relevant, tests should be designed and data analyzed 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).

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 at pF = 0 and pF = 2.5 must 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 that as far as possible the same soils be used 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 distribution 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 absorption/desorption studies.

The first soil chosen to begin testing should not have extreme characteristics 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 must 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—

— indentify, where feasible, the relative importance of the types of process involved (balance between chemical and biological degradation),

— 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, 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.

Non-extractable residues 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 generated through metabolic pathways which form naturally occurring 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, as well as in the form of balance sheets which show the distribution of radiolabel as a function of time, as between—

— active substance,

— CO2,

— volatile compounds other than CO2,

— 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 such residues exceed 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 should normally be 120 days, except where after a shorter period the levels of non-extractable residues and CO2 are such that they can be extrapolated in a reliable way to 100 days.

Test guideline

The methodology to be used is that described by SETAC⁹.

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 active substance, following use of plant protection products containing it, to anaerobic conditions is unlikely to occur,

Test conditions and test guideline

The provisions specified 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

The methodology to be used is that described by SETAC⁹.

7.1.1.2

Rate of degradation

7.1.1.2.1

Laboratory studies

Aim of the tests

The soil degradation studies should provide the 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, degradation 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 of additional to that referred to in paragraph 7.1.1.1.1 must be reported.

In order to investigate the influence of temperature on degradation, until such time as a validated Community calculation model for the extrapolation of degradation rates to low temperatures is available, one additional study at 10 °C has to be performed on one of the soils used for the investigation of degradation at 20 °C.

The duration of the study should normally be 120 days except where 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 DT50 values were determined from the results obtained with the active substance.

Test guideline

The methodology to be used is that described by SETAC⁹.

Anaerobic degradation

Circumstances in which required

The rate of anaerobic degradation of the active substance must be reported where an anaerobic study is required in accordance with 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 in accordance with point 7.1.1.1.2.

The duration of the study should normally be 120 days except where more than 90% of the active substance is degraded before that period expires.

Similar studies using one soil 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 DT₅₀ values were determined from the results obtained with the active substance.

Test guideline

The methodology to be used is that described by SETAC⁹.

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, information on relevant metabolites, degradation and reaction products must also be reported.

Circumstances in which required.

Tests must be conducted where DT50lab, determined at 20 °C and at a soil moisture content pF value of 2 - 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 DT50lab determined at 10 °C and at a soil moisture content pF value of 2 - 2.5 (suction pressure) is greater than 90 days.

Test conditions

Individual studies on a range of representative soils (normally 4 different types) must be continued until> 90% of the amount applied has dissipated. The maximum duration of such studies is 24 months.

Test guideline

The methodology to be used is that described by SETAC⁹.

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 where the DT_50lab is greater than one third of the period between the time of application and time of harvest and where absorption by the succeeding crop is possible, except where soil residues at time of sowing or planting of a succeeding crop can be reliably estimated from the data generated in 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 has dissipated at earlier date.

Test guideline

The methodology to be used is that described by SETAC⁹.

Soil accumulation studies

Aim of the tests

The tests should provide sufficient data to evaluate the possibility of accumulation in soil 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 DT90f> 1 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 must 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 adsorption coefficient of the active substance and of relevant metabolites, degradation and reaction products.

Circumstances in which required.

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 treatments for trees.

Test 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

The test must be carried out in accordance with OECD Guideline 106.

7.1.3

Mobility in the soil

7.1.3.1

Column leaching studies

Aim of the test

Testing should provide sufficient data to evaluate the mobility and leaching potential of the active substance and if possible of relevant metabolites, degradation and reaction products.

Circumstances in which required

Studies in 4 soils must be carried out where in the adsorption and desorption studies provided for under point 7.1.2 it is not possible to obtain reliable adsorption coefficient values.

Test guideline

The methodology to be used is that described by SETAC⁹.

7.1.3.2

Aged residue column leaching

Aim of the test

Testing 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 with point 7.1.2 or 7.1.3.1 was performed.

Test conditions

The period(s) of ageing should be determined on the basis of the degradation patterns of active substance and metabolites and be such as to ensure that a relevant spectrum of metabolites is present and the time of leaching.

Test guideline

The methodology to be used is that described by SETAC9.

7.1.3.3

Lysimeter Studies or Field leaching studies

Aim of the tests

The test should provide data with respect to—

— mobility in soil,

— potential for leaching to ground water,

— the potential distribution in soil.

Circumstances in which required

Expert judgement is 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 (PECGW) calculated in accordance with the provisions of Annex 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 the design of both experimental installations and of individual studies, to ensure that results obtained can be used for assessment purposes. Studies should cover the realistic worst case situation likely to arise, taking into account soil type, climatic conditions, application rate and frequency and period of application.

Water percolating from soil columns must be analysed at suitable intervals, while residues in plant material must be determined at harvest. Residues in the soil profile, in at least 5 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 removal of soil cores influences the leaching process.

Precipitation, soil and air temperatures must be recorded at regular intervals (at least on a weekly base).

Lysimeter studies

Test conditions

The minimal depth of the lysimeters should be 100 cm and their maximal depth should be 130 cm. The soil cores must not be disturbed. 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 to a depth of more than 25 cm.

Field leaching studies

Test conditions

Information relative to the groundwater table in the fields used for experimental purposes 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

The methodology to be used is that described by SETAC⁹.

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, and

— potential for contamination of surface water and groundwater.

7.2.1

Route and rate of degradation in aquatic systems (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, degradation 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, degradation 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 guidelines

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 in accordance with the provisions of Annex VI of the Directives of 1967, for the classification of the active substance.

Test guideline

The test must be carried out in accordance with EEC Method C 4.

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

The methodology to be used is that described by SETAC⁹.

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 groundwater.

Test conditions

Expert judgement is required to decide whether, or not, this information is necessary. Before performing these studies the applicant must 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 that occur in soil, water or air, resulting from use, or proposed use, of plant protection products 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 on the active substance

8.1

Effects on birds

8.1.1

Acute oral toxicity

8.1.2

Short-term toxicity — eight-day dietary study in at least one species (other than chicken)

8.1.3

Effects on reproduction

8.2

Effects on aquatic organisms

8.2.1

Acute toxicity to fish

8.2.2

Chronic toxicity to fish

8.2.3

Effects on fish reproduction and growth rate

8.2.4

Bioaccumulation in fish

8.2.5

Acute toxicity for Daphnia magna

8.2.6

Daphnia magna reproduction and growth rate

8.2.7

Effects on algal growth

8.3

Effects on other non-target organisms

8.3.1

Acute toxicity to honeybees and other beneficial arthropods (e.g. predators)

8.3.2

Toxicity to earthworms and to other soil non-target macro-organisms

8.3.3

Effects on soil non-target micro organisms

8.3.4

Effects on other non-target organisms (flora and fauna) believed to be at risk

8.3.5

Effects on biological methods for sewage treatment

9

Summary and evaluation of points 7 and 8

10

Proposals including justification for the proposals for the classification 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 Annex III, part A, for a representative plant protection product

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 referred to or described in this Annex; in the case of studies initiated before the adoption of the modification of this Annex, the information shall be generated using suitable internationally or nationally validated test guidelines or, in the absence thereof, test guidelines accepted by the competent authority;

1.3

in the event of a test guideline being inappropriate or not described, or where another one than those referred to in this annex has been used, include a justification, which is acceptable to the competent authority for the guidelines used;

1.4

include, a full description of test guidelines used, except if they are referred to or described in this Annex, and a full description of any deviations from them including a justification, which is acceptable to the competent authority, 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 competent authority 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 principles laid down in Directive 87/18/EEC, where testing is done to obtain data on the properties and/or safety with respect to human health or the environment.

2.2

Tests and analyses, required under the provisions of section 6 points 6.2 to 6.6 of this annex, shall, where they are conducted outside the territory of the state, be conducted by official or officially recognised testing facilities or organisations in the Member State concerned, which satisfy at least the requirements specified in points 2.2 and 2.3 of the introduction to Annex III to Directive 93/71/EEC.

2.3

Tests and analyses, required under the provisions of section 6 points 6.2 to 6.6 of this annex, shall, where they are conducted within the territory of the state, be conducted in accordance with the Principles of Good Experimental Practice set out in the Sixth Schedule, or in compliance with Irish/European Standard IS/EN 45001 and in accordance with the authorisation for trials or trials permit concerned.

2.4

Notwithstanding the provisions of point 2.1, during the period to 31 December 1999, tests and analyses done to obtain data on the properties and/or safety with respect to honeybees and beneficial arthropods other than bees may have been conducted by officially recognised testing facilities or organisations, in accordance with the principles laid down in the Sixth Schedule, or in compliance with Irish/European Standard IS/EN 45001, where they are conducted within the territory of the state, and in accordance with the requirements of points 2.2 and 2.3 of the introduction to Annex III to Directive 93/71/EEC, where they are conducted outside the territory of the state.

3

The information required shall include the proposed classification and labelling of the plant protection product in accordance with relevant Community Directives.

4

In individual cases it may be necessary to require certain information as provided for in Annex II, Part A, for formulants. Before such information will be required and before possibly new studies have to be performed, all information on the formulant, made available to the competent authority, shall 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 of 27 June 1967, on the approximation of laws, regulations and administrative provisions relating to the classification, packaging and labelling of dangerous substances.

1

Identity of the plant protection product

The information provided, taken together with that provided for the active substance(s), must be sufficient to identify preparations, with precision, and to 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 territory of the State, 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 (preferably 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 Annex II had not been submitted previously, a statement of purity and detailed information on the impurities as required in Annex II must 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 plant protection products already authorised).

1.4

Detailed quantitative and qualitative information on the composition of the preparation (active substance(s), and formulant(s)

1.4.1

For preparations the following information must be reported—

— the content of both technical active substance(s) and pure active substance(s); and

— the content of formulants.

The concentrations must be expressed in terms as provided for in Article 6(2) of the Directive of 1978.

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 the Directive of 1967, or, if not included in that Directive, in accordance with both IUPAC and CA nomenclature. Their structure or structural formula must be provided. For each component of 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)

preservative

antifoaming agent

odourant

antifreeze

perfume

binder

propellant

buffer

repellent

carrier

safener

deodorant

solvent

dispersing agent

stabiliser

dye

synergist

emetic

thickener

emulsifier

wetting agent

fertiliser

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 in accordance with 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 that publication, 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

plant growth regulator

bactericide

repellent

fungicide

rodenticide

herbicide

semio-chemicals

insecticide

talpicide

molluscicide

viricide

nematicide

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 Specifications, of the FAO Panel of Experts on Pesticide Specifications, Registration Requirements and Application Standards, must be stated. Divergences from FAO specifications 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 oxidising properties

2.2.1

The explosive properties of preparations must be determined in accordance with EEC Method A 14 and be reported. 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

The oxidising properties of preparations which are solids, must be determined in accordance with EEC Method A 17 and be reported. For other preparations the method used must be justified. Oxidising properties 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 in accordance with EEC Method A 9 and be reported. The flammability of solid preparations and gasses must be determined in accordance with EEC Method A 10, A 11 or A 12, as appropriate, and be reported. The auto-flammability of preparations, determined in accordance with EEC Method A 15 or A 16 as appropriate, and/or, where necessary, in accordance with the UN-Bowes-Cameron-Cage-Test (UN-Recommendations on the Transport of Dangerous Goods, Chapter 14, Nr 14.3.4), must be reported.

2.4

Acidity/alkalinity and if necessary pH value

2.4.1

In the case of preparations which are acidic (pH10) the acidity or alkalinity and the pH value must be determined in accordance with CIPAC Method MT31 and MT75 respectively, and be reported.

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 in accordance with CIPAC Method MT75 and be reported.

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 in accordance with OECD Test Guideline 14 and be reported.

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 must be determined in accordance with EEC Method A 5 and be reported.

2.6

Relative density and bulk density

2.6.1

The relative density of liquid preparations must be determined in accordance with EEC Method A 3 and be reported.

2.6.2

The bulk (tap) density of preparations which are powders or granules, must be determined in accordance with CIPAC Methods MT33, MT159 or MT169, as appropriate, and be reported.

2.7

Storage stability — stability and shelf-life. Effects of light, temperature and humidity on technical characteristics of the plant protection product

2.7.1

The stability of the preparation after storage for 14 days at 54°C must be determined in accordance with CIPAC Method MT46 and be reported.

Other storage times and/or temperatures may be needed (e.g. 8 weeks at 40°C or 12 weeks at 35°C or 18 weeks at 30°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 initial determined content, the minimum content must be declared and information on the degradation products must be supplied.

2.7.2

Additionally in the case of liquid preparations, the effect of low temperatures on stability, must be determined in accordance with CIPAC Methods MT39, MT48, MT51 or MT54, as appropriate, and be reported.

2.7.3

The shelf life of the preparation at ambient temperatures must be reported. Where shelf life is less than two years, the shell life in months, with appropriate temperature specifications, must be reported. Useful information relating to such testing is contained 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 in accordance with CIPAC Method MT53.3 and be reported.

2.8.2

Persistent foaming

The persistence of foaming of preparations to be diluted with water, must be determined in accordance with CIPAC Method MT47 must be reported.

2.8.3

Suspensibility and suspension stability

2.8.3.1

The suspensibility of water dispersible products (e.g. wettable powders, water dispersible granules, suspension concentrates) must be determined in accordance with CIPAC Method MT15, MT161 or MT168, as appropriate and be reported.

2.8.3.2

The spontaneity or dispensability of water dispersible products (e.g. suspension concentrates and water dispersible granules) must be determined in accordance with CIPAC Methods MT160 or MT174, as appropriate, and be reported.

2.8.4

Dilution stability

The dilution stability of water soluble products must be determined in accordance with CIPAC Method MT41 and be reported.

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 in accordance with CIPAC Method MT59.1 and be reported.

In the case of water dispersible products, a wet sieve test must be conducted in accordance with CIPAC Method MT59.3 or MT167, as appropriate, must be reported.

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 in accordance with OECD Method 110 and be reported.

The nominal size range of granules for direct application must be determined in accordance with CIPAC MT58.3 and for water dispersible granules and in accordance with CIPAC MT170, and be reported.

2.8.6.2

The dust content of granular preparations, must be determined in accordance with CIPAC Method MT171 and be reported. If relevant for operator exposure the particle size of dust must be determined in accordance with OECD Method 110 and be reported.

2.8.6.3

The friability and attrition characteristics of granules, must be determined and reported once internationally agreed methods are available. Where relevant data are available they must be reported together with details of the method used.

2.8.7

Emulsifiability, Re-emulsifiability, emulsion stability

2.8.7.1

The emulsifiability, emulsion stability and re-emulsifiability of preparations which form emulsions, must be determined in accordance with CIPAC Methods MT36 or MT173, as appropriate, and be reported.

2.8.7.2

The stability of dilute emulsions and of preparations which are emulsions, must be determined in accordance with CIPAC Method MT20 or MT173, as appropriate, and be reported.

2.8.8

Flowability, pourability (rinsability) and dustability

2.8.8.1

The flowability of granular preparations must be determined in accordance with CIPAC Method MT172 and be reported.

2.8.8.2

The pourability (including rinsed residue) of suspensions (e.g. suspension concentrates, suspo-emulsions), must be determined in accordance with CIPAC Method MT148 and be reported.

2.8.8.3

The dustability of dustable powders following accelerated storage as specified in paragraph 2.7.1 must be determined in accordance with CIPAC Method MT34 or another suitable method and be reported.

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 determined using in-house test methods and be reported. A practical test is an acceptable alternative.

2.9.2

The chemical compatibility of tank mixes must be determined and reported except where examination of the individual properties of the preparations establishes 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 determining 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 in accordance with CIPAC Method MT175.

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

— Agriculture

— Horticulture

— Forestry

— 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

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)

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

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 fertilisation etc. must be reported.

3.4

Application rate

For each method of application and each use, the rate of application per unit (ha, mm³ ) 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/m³ and where appropriate in g or kg/tonne; for protected crops and home gardening use rates shall be expressed in g or kg/100mor g or kg/m³.

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, indicating 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 in accordance with ADR Methods 3552, 3553, 3560, 3554, 3555, 3556 and 3558, or ADR methods for intermediate bulk containers, as appropriate, and where child resistant closures are required, in accordance with ISO Standard 8317, and be reported.

4.1.3

The resistance of the packaging material to its contents must be determined in accordance with GIFAP Monograph No. 17, and be reported.

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 or on 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 test results, information on any specific agricultural, plant health or environmental conditions under which the preparation may or may 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 must be conducted in accordance with ISO-TR 9122.

Where relevant, the nature and characteristics of protective clothing and equipment proposed must be reported. The data provided must be sufficient to permit an evaluation to be made of the suitability and effectiveness of the protective clothing under realistic conditions of use (e.g. shield 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 procedures for—

— containment of spillages;

— decontamination of areas, vehicles and buildings;

— disposal of damaged packaging, adsorbents and other materials;

— protection of emergency workers and bystanders; and

— 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 neutralisation

Neutralisation 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 neutralisation should be identified (through analysis or on the basis of theoretical considerations) and be 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 them, 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 residence time), at 800°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

5.1

Analytical methods for determining the composition of the plant protection product

5.2

In so far as not covered by Annex II, Part A, point 4.2, analytical methods including recovery rates and the limits of determination for residues and where relevant on, the following:

5.2.1

Treated plants, plant products, foodstuffs, feeding-stuffs

5.2.2

Soil

5.2.3

Water (including drinking water)

5.2.4

Air

5.2.5

Animal and human body fluids and tissues

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 active 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 products 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 in the opinion of the applicant the trials from the first season adequately confirm the validity of claims made on the basis of extrapolation of results from other crops, commodities or situations or from tests with closely similar preparations, a justification, which is acceptable to the competent authority for not carrying out a second seasons 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

Preliminary tests

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 competent authority. These reports will provide additional information for the competent authority when it evaluates the plant protection product. Where this information is not submitted a justification which is acceptable to the competent authority must be provided.

6.2

Testing effectiveness

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 authorised plant protection product which has proved to have a sufficient performance in practice under the agricultural, 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, operational 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 or 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 show 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 recommended 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 product is unlikely to be affected to a significant degree by environmental factors, such as temperature or rain, an investigation 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 is 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 Organisation (EPPO) guidelines 152 and 181. The report shall include a detailed and critical assessment of the data.

When conducted within the territory of the state, the trials must be carried out in accordance with specific EPPO guidelines, where available. When conducted within the territory of another Member State, the trials must be carried out in accordance with specific EPPO guidelines, where available or when the Member State concerned so requires, in accordance with guidelines satisfying at least the requirements of the corresponding EPPO guidelines.

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

Information on the occurrence or possible 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 populations of harmful organisms to the active substance(s), or to related active substances, must be provided. Where such information is not directly relevant to the uses for which authorisation is sought or to be renewed (different species of harmful organism or different crops), it must, if available, nevertheless be provided, as it may provide an 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

Effects on the yield of treated plants or plant products in terms of quantity and/or quality

6.4.1

Effects on the quality of plants or plant products

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 product 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 substance 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 its use could have an adverse influence on other quality aspects (for example in the case of use of plant growth regulators close to harvest), or

— other products based on the same or a closely similar active substance 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 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 and methods of processing the crops, if relevant, 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 possibility 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 substance 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 authorised.

6.4.3

Effects on the yield of treated plants or plant products

Aim of the tests

The tests shall provide sufficient data to permit an evaluation of the performance of the plant protection product and of the 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 plants or 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 storage 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

Phytotoxicity to target plants (including different cultivars), or to target plant products

Aim of the tests

The tests 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 to be transient, evidence to support this claim is required. If necessary yield measurements 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 growth stage, vigour, and other factors which may influence susceptibility 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) or adjuvant(s), the provision of the previous paragraphs apply for the mixture.

Test guideline

Observations concerning phytotoxicity must be recorded and reported 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, where testing is conducted within the territory of the state. When conducted within the territory of another Member State, the trials must be carried out in accordance with EPPO Guideline 135, or when the Member State concerned so requires, in accordance with guidelines satisfying at least the requirements of EPPO Guideline 135.

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

Observations on undesirable or unintended side-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 significant 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 succeeding 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 indications 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

For seeds testing shall be done according to ISTA methods¹⁴.

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 environmental effects must also be reported, especially effects on wildlife and/or beneficial organisms.

6.7

Summary and evaluation of data presented under 6.1 to 6.6

A summary of all data and information 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 the evaluation of the toxicity of preparations, sufficient information concerning the acute toxicity, irritancy and sensitizing properties of their active substance(s) is necessary. Where possible, additional information on mode of toxic action, toxicological profile and all other known toxicological aspects of the active substance(s) 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 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, and in particular to establish or indicate—

— the toxicity of the plant protection product,

— the toxicity of the plant protection product relative to that of the active substance,

— the time course and characteristics of the effects with full details of behavioural changes and possible gross pathological changes at postmortem,

— 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 plant protection product to be classified in accordance with the Directive of 1978. 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 toxicity test should always be carried out unless the applicant can establish to the satisfaction of the competent authority that Article 3.2 of the Directive of 1978 can be invoked.

Test Guideline

The test must be carried out in accordance with EEC Method B 1 or B 1 bis.

7.1.2

Percutaneous

Circumstances in which required

An acute percutaneous toxicity test should always be carried out unless the applicant can establish to the satisfaction of the competent authority that Article 3.2 of the Directive of 1978 can be invoked.

Test Guideline

The test must be carried out in accordance with EEC Method B 3.

7.1.3

Inhalation

Aim of the test

The test will provide information concerning the inhalation toxicity to rats of the plant protection product or of smoke generated from it.

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 a fumigant,

— is used with fogging equipment,

— is a vapour releasing preparation,

— is an aerosol,

— is a powder containing a significant proportion of particles of diameter1% 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 x 10-2 Pa and is to be used in enclosed spaces such as warehouses or glasshouses,

— is to be applied in a manner which generates a significant proportion of particles or droplets of diameter1% on a weight basis).

Test Guideline

The test must be carried out in accordance with EEC Method B 2.

7.1.4

Skin irritation

Aim of the test

The test will provide information as to the potential for 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 and reported 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 EEC Method B 4.

7.1.5

Eye irritation

Aim of the test

The test will provide information as to the potential for eye irritancy of the plant protection product, including the potential reversibility of the effects observed.

Circumstances in which required

Eye irritation tests must be conducted and reported except where it is likely, as indicated in the test guideline, that severe effects on the eye may be produced.

Test Guideline

The test must be carried out in accordance with EEC Method B 5.

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 test must always be carried out except where the active substance(s) or co-formulants are known to have sensitizing properties.

Test Guideline

The test must be carried out in accordance with EEC Method B 6.

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 tests as referred to in 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 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 combination of the products concerned and available information or practical experience with the products concerned or similar products.

7.2

Data on exposure

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 form of the product (undiluted/diluted), and the route, degree and duration of exposure. Sufficient information and data must be generated and reported to permit an assessment to be made 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 for its use. The data and information provided 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 calculation model, in order to permit an evaluation to be made of the degree of 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 arising from the application of the classification and labelling provisions of the Directive of 1978. The estimation made shall relate to exposure arising from handling the undiluted and diluted product, taking into account the different types and sizes of containers to be used, mixing and loading operations, application of the plant protection product, climatic conditions and cleaning and the routine maintenance of application equipment.

A first estimation shall be made on the basis of the assumption that the operator does not use any personal protective equipment.

Where appropriate, a second estimation shall be made on the basis of an assumption that the operator uses that effective and readily obtainable protective equipment which it is feasible for the operator to use. Where personal protective measures are specified on the label, the estimation shall 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 to be made of the degree of operator exposure likely to arise under the proposed conditions of use.

Circumstances in which required

Actual exposure data for relevant exposure route(s) must be reported where risk assessment indicates that a health-based limit value may be exceeded. That will 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 the inclusion of the active substance(s) in Annex 1, and/or

— the Limit Values established for the active substance(s) and/or toxicologically relevant compound(s) contained in the plant protection product, in accordance with Council Directive 80/1107/EEC¹² and Council Directive 90/394/EEC¹⁵, on the protection of workers from the risks related to exposure to carcinogens at work,

may be exceeded.

Actual exposure data must also be reported when an appropriate calculation model or appropriate data are not available to permit an estimation to be made as provided for in 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 to be used in refining the estimation made in accordance with point 7.2.1.1

Test conditions

The test must be conducted 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 for the protection of bystanders, 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 calculation model, in order to permit an evaluation to be made of the degree of 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 shall be made for each type of application method. The estimation shall be made on the basis of the assumption that bystanders do not use any personal protective equipment.

Measurement of bystander exposure may be required when estimates made indicate that there is 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 when 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 protection measures, including waiting and re-entry periods.

7.2.3.1

Estimation of worker exposure

Aim of the estimation

An estimation shall be made, using where available a suitable calculation model, in order to permit an evaluation to be made of the degree of worker exposure likely to arise under the proposed conditions of use.

Circumstances in which required

An 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.

A first estimation made with the benefit of available data on the exposure likely to arise shall be made on the basis of the assumption that the worker does not use any personal protective equipment.

Where appropriate, a second estimation shall be made on the basis of an assumption that the worker uses that effective and readily obtainable protective equipment which it is feasible for the worker to use.

Where appropriate, a further estimation shall be made using data generated relating to the amounts of dislodgeable residues that occur 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 to be made of the degree of worker exposure likely to arise under the proposed conditions of use.

Circumstances in which required

Actual exposure data for relevant exposure route(s) must be reported where risk assessment indicates that a health-based limit value be exceeded. That will be the case when the results of the estimation of worker exposure provided for under point 7.2.3.1 indicate that—

— the AOELs established in the context of the inclusion of the active substance(s) in Annex 1, and/or

— the Limit Values established for the active substance(s) and/or toxicologically relevant compound(s) contained in the plant protection product, in accordance with Council Directive 80/1107/EEC¹² and Council Directive 90/394/EEC¹⁵,

may be exceeded.

Actual exposure data must also be reported when an appropriate calculation model or appropriate data are not available to permit an estimation to be made as provided for in point 7.2.3.1.

In cases 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 to be used in refining the estimation made in accordance with point 7.2.3.1.

Test conditions

The test must be conducted 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 of toxicologically relevant compounds through the skin.

Circumstances in which required

The study must be conducted when dermal exposure is a significant route and where the risk assessment indicates that a health-based limit value may be exceeded. That will be the case when 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 AOELs established in the context of the inclusion of the active substance(s) in Annex I, and/or

— the Limit Values established for the active substance(s) and/or toxicologically relevant compound(s) contained in the plant protection product, in accordance with Council Directive 80/1107/EEC¹² and Council Directive 90/394/EEC¹⁵,