Commission Directive 94/79/EC of 21 December 1994 amending Council Directive 91/414/EEC concerning the placing of plant protection products on the market

• Coming into Force: 01 February 1995
• End of Effective Date: 13 June 2011
• Celex Number: 31994L0079
• ELI: http://data.europa.eu/eli/dir/1994/79/oj
• Published date: 31 December 1994
• Date: 21 December 1994
• Official Gazette Publication: Official Journal of the European Communities, L 354, 31 December 1994

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31994L0079

Commission Directive 94/79/EC of 21 December 1994 amending Council Directive 91/414/EEC concerning the placing of plant protection products on the market

Official Journal L 354 , 31/12/1994 P. 0016 - 0031
Finnish special edition: Chapter 3 Volume 65 P. 0224
Swedish special edition: Chapter 3 Volume 65 P. 0224

COMMISSION DIRECTIVE 94/79/EC of 21 December 1994 amending Council Directive 91/414/EEC concerning the placing of plant protection products on the market

THE COMMISSION OF THE EUROPEAN COMMUNITIES,

Having regard to the Treaty establishing the European Community,

Having regard to Council Directive 91/414/EEC of 15 July 1991 concerning the placing of plant protection products on the market (1), as last amended by Directive 94/43/EC (2), and in particular Article 18 (2) thereof,

Whereas Annexes II and III to Directive 91/414/EEC set out the requirements for the dossier to be submitted by applicants respectively for the inclusion of an active substance in Annex I and for the authorization of a plant protection product;

Whereas it is necessary to indicate, in Annexes II and III, to the applicants, as precisely as possible, any details on the required information, such as the circumstances, conditions and technical protocols under which certain data have to be generated; whereas these provisions should be introduced as soon as available in order to permit applicants to use them in the preparation of their files;

Whereas it is now possible to introduce more precision with regard to the data requirements concerning toxicological and metabolism studies on the active substance provided for in Section 5 of Part A of Annex II;

Whereas it is also now possible to introduce more precision with regard to the data requirements concerning toxicological studies on the plant protection product provided for in Section 7 of Part A of Annex II;

Whereas the measures provided for in this Directive are in accordance with the opinion of the Standing Committee on Plant Health,

HAS ADOPTED THIS DIRECTIVE:

Article 1

Directive 91/414/EEC is amended as follows:

1. in Part A of Annex II the section headed '5. Toxicological and metabolism studies on the active substance' is replaced by Annex I hereto;

2. in Part A of Annex III the section headed '7. Toxicological studies' is replaced by Annex II hereto;

3. Point 1.2 of the introduction to Annexes II and III is replaced by the following: '1.2 where relevant, be generated using test guidelines, according to the latest adopted version, referred to or described in this Annex; in the case of studies initiated before the entry into force 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;'

4. in point 1.3 of the introduction to Annexes II and III, the following words are added at the end: 'in particular, when reference is made in this Annex to an EEC Method which consists in the transposal of a method developed by an international organization (e.g. OECD), Member States may accept that the required information is generated according to the latest version of that method if at the initiation of the studies the EEC Method has not yet been updated;'.

Article 2

Member States shall bring into force the laws, regulations and administrative provisions necessary to comply with this Directive by 31 January 1996. They shall immediately inform the Commission thereof.

When Member States adopt these provisions, these shall contain a reference to this Directive or shall be accompanied by such reference at the time of their official publication. The procedure for such reference shall be adopted by Member States

Article 3

This Directive shall enter into force on 1 February 1995.

Article 4

This Directive is addressed to the Member States.

Done at Brussels, 21 December 1994.

For the Commission

René STEICHEN

Member of the Commission

(1) OJ No L 230, 19. 8. 1991, p. 1.(2) OJ No L 227, 1. 9. 1994, p. 31.

ANNEX I

'5. TOXICOLOGICAL AND METABOLISM STUDIES

Introduction

(i) The information provided, taken together with that provided for one or more preparations containing the active substance, must be sufficient to permit an evaluation to be made as to the risks for man, associated with the handling and use of plant protection products containing the active substance, and the risk for man arising from residual traces remaining in food and water. In addition, the information provided must be sufficient to:

- permit a decision to be made as to whether, or not, the active substance can be included in Annex I,

- specify appropriate conditions or restrictions to be associated with any inclusion in Annex I,

- classify the active substance as to hazard,

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

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

- specify the hazard symbols, the indications of danger, and the risk and safety phrases for the protection of man, animals and the environment to be included in packaging (containers),

- identify relevant first aid measures as well as appropriate diagnostic and therapeutic measures to be followed in the event of poisoning in man, and

- permit an evaluation to be made as to the nature and extent of the risks for man, animals (species normally fed and kept or consumed by man) and of the risks for other non-target vertebrate species.

(ii) There is a need to investigate and report all potentially adverse effects found during routine toxicological 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 reported.

(iii) In the context of the influence that impurities can have on toxicological behaviour, it is essential that for each study submitted, a detailed description (specification) of the material used, as mentioned under section 1 point 11 be provided. Tests should be conducted using active substance of that specification to be used in the manufacture of preparations to be authorized, except where radiolabelled material is required or permitted.

(iv) Where studies are conducted using an active substance produced in the laboratory or in a pilot plant production system, the studies must be repeated using the active substance as manufactured, unless it can be justified that the test material used is essentially the same, for the purposes of toxicological testing and assessment. In cases of uncertainty, appropriate bridging studies must be submitted to serve as a basis for a decision as to the possible need for repetition of the studies.

(v) In the case of studies in which dosing extends over a period, dosing should preferably be done using a single batch of active substance if stability permits.

(vi) For all studies actual achieved dose in mg/kg body weight, as well as in other convenient units, must be reported. Where dosing via the diet is utilized the test compound must be distributed uniformly in the diet.

(vii) Where, as a result of metabolism or other processes in or on treated plants, or as a result of processing of treated products, the terminal residue (to which consumers or workers as defined in 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 these components of the terminal residue unless it can be demonstrated that consumer or worker exposure to these substances does not constitute a relevant risk to health. Toxicokinetic and 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 way of administration of the test substance depends on the main exposure routes. In cases where exposure is mainly by the gas phase, it can be more appropriate to perform inhalation studies instead of oral studies.

5.1. Studies on absorption, distribution, excretion and metabolism in mammals

Quite limited data, as described below and restricted to one test species (normally the rat) may be all that is required in this area. These data can provide information useful in the design and interpretation of subsequent toxicity tests. However, it must be remembered that information on interspecies differences may be crucial in extrapolation of animal data to man and information on percutaneous penetration, absorption, distribution, excretion and metabolism may be useful in operator risk assessments. It is not possible to specify detailed data requirements in all areas, since the exact requirements will be dependant upon the results obtained for each particular test substance.

Aim of the test:

The tests should provide sufficient data to permit:

- an evaluation of the rate and extent of absorption,

- the tissue distribution and the rate and extent of excretion of the test substance and the relevant metabolites,

- the identification of metabolites and the metabolic pathway.

The effect of dose level on these parameters and whether results are different after single versus repeated doses, should also be 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...