Commission Regulation (EU) No 284/2013 of 1 March 2013 setting out the data requirements for plant protection products, in accordance with Regulation (EC) No 1107/2009 of the European Parliament and of the Council concerning the placing of plant protection products on the market Text with EEA relevance

Possible human health hazards related to pathogenic events linked to the use of the plant protection product are addressed through data on infectivity, pathogenicity, and clearance of the active substance that is a micro-organism in accordance with Section 5 of Part B of the Annex to Regulation (EU) No 283/2013.

Studies to determine the potential toxicity of the plant protection product shall be performed as required in point 7.3, unless the applicant demonstrates by following a weight of evidence approach, based on the information provided under Sections 2, 3, 4 and point 7.1 or retrieved from any other reliable sources (e.g. Integrated Approach to Testing and Assessment – IATA, CLP calculation rules in accordance with Regulation (EC) No 1272/2008 or read-across data from similar preparations) that no such effects are to be expected. An assessment of the potential toxicity of the plant protection product shall be submitted, taking into consideration information on the intrinsic properties of co-formulants, metabolites of concern identified in accordance with point 2.8 of Part B of the Annex to Regulation (EU) No 283/2013, relevant impurities, with consideration for possible adverse synergistic effects and/or interaction between them and with the proposal for classification and labelling. With this assessment, the applicant shall demonstrate whether or not sufficient information is available to classify the plant protection product in accordance with Regulation (EC) No 1272/2008 with regard to toxicity to humans and whether or not acute toxicity studies on animals as described in points 7.3.1 to 7.3.6 are needed.

7.3.   Acute toxicity

Unless information can be provided to allow an assessment to be conducted on the possible human toxicity of the plant protection product as set out in point 7.2, the applicant shall define which of the tests described in points 7.3.1 to 7.3.6 is relevant for the plant protection product and perform the test(s) identified in accordance with the instruction provided in each respective relevant point. The studies indicated in points 7.3.1 to 7.3.6, data and information to be provided and evaluated shall 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 acute toxicity of the plant protection product,

• — the time course and characteristics of the adverse effect with full details of behavioural changes and possible gross toxicological findings at post-mortem in animal studies,

• — where possible, the mode of toxic action, and

• — the relative hazard associated with the different routes of exposure.

The information generated shall also permit the plant protection product to be classified in accordance with Regulation (EC) No 1272/2008.

7.3.1.   Acute oral toxicity

Unless information can be provided to allow an assessment to be conducted on the possible acute oral toxicity of the plant protection product as set out in point 7.2, a test for acute oral toxicity shall be carried out in accordance with the most appropriate guidelines.

7.3.2.   Acute dermal toxicity

Unless information can be provided to allow an assessment to be conducted on the possible dermal toxicity of the plant protection product as set out in point 7.2, a test for dermal toxicity shall be carried out in accordance with the most appropriate guidelines.

7.3.3.   Acute inhalation toxicity

Unless information can be provided to allow an assessment to be conducted on the possible inhalation toxicity of the plant protection product as set out in point 7.2, a test for acute inhalation toxicity shall be carried out if the plant protection product:

• — is used with fogging equipment,

• — is used as a smoke generating formulation,

• — is used as a vapour releasing preparation,

• — is to be applied from aircraft in cases where inhalation exposure is relevant (broadcast air-assisted sprayer),

• — is an aerosol,

• — is a powder containing a significant proportion of particles of diameter < 50 micrometre (> 1 % on a weight basis),

• — is to be applied in a manner which generates a significant proportion of particles or droplets of diameter < 50 micrometre (> 1 % on a weight basis), or

• — contains a volatile component at greater than 10 %.

7.3.4.   Skin irritation

Unless information can be provided to allow an assessment to be conducted on the skin irritation potential of the plant protection product from the available information regarding its components, including the active substance, co-formulants, safeners, synergists, and relevant impurities as set out in point 7.2, a test for skin irritation shall be carried out in accordance with the most appropriate guidelines.

The test shall provide the potential of skin irritancy of the plant protection product including the potential reversibility of the effects observed.

7.3.5.   Eye irritation

A test for eye irritation shall be carried out in accordance with the most appropriate guidelines, unless:

• — information can be provided to allow an assessment to be conducted on the eye irritating potential of the plant protection product as set out in point 7.2, or

• — the micro-organism is an already known eye irritant or it is likely, as indicated in the test guideline, that severe effects on the eyes may be produced.

The test shall provide the potential for eye irritation of the plant protection product, including the potential reversibility of the effects observed.

7.3.6.   Skin sensitisation

Unless information can be provided to allow an assessment to be conducted on the skin sensitisation properties of the plant protection product from the available information regarding its chemical components (i.e. co-formulants, metabolites of concern and relevant impurities) as set out in point 7.2, a test for skin sensitisation when available, shall be carried out in accordance with the most appropriate guidelines.

7.4.   Additional toxicity information

If, based on results of the studies required in point 7.3, one or more substances of concern is present in the plant protection product (e.g. metabolites of concern and/or co-formulants) for which the risk is for human and animal health is considered not acceptable based on those studies already performed, relevant additional information on toxicity may be necessary for the plant protection product. The need to perform supplementary studies on the plant protection product shall be based on expert judgement case-by-case, in the light of the particular parameters to be investigated and the objectives to be achieved, for example, if concern on the toxicity of the plant protection products has arisen from studies described in points 7.3.1 to 7.3.6 or a conclusion on toxicity could not be reached.

7.5.   Data on exposure

If, based on data provided in Section 5 of Part B of the Annex to Regulation (EU) No 283/2013 and this Section, effects on human health cannot be excluded, sufficient information and data shall be generated and reported to permit an assessment of the extent of exposure to the plant protection product likely to occur under the proposed conditions of use. Study design shall take into account biological, physical, chemical and toxicological properties of the plant protection product as well as the type of the product (undiluted/diluted), preparation type, and the route, the degree and duration of exposure.

In the case where there is a particular concern for a possibility of dermal absorption of a toxic component of the plant protection product based on information provided in this Section, dermal absorption data shall be provided as provided for under point 7.3 of Part A.

Results from exposure monitoring during production and use of the plant protection product shall be submitted.

The information and data referred to in this point shall provide the basis for the selection of appropriate protective measures including personal protective equipment (see point 4.2) to be used by operators and workers and other appropriate risk mitigation measures (e.g. for bystanders and residents) and to be specified on the label.

7.6.   Available toxicological data relating to non-active substances

Where relevant, the following information shall be submitted for each co-formulants, safeners and synergists:

• (a) the registration number as referred to in Article 20(3) of Regulation (EC) No 1907/2006 of the European Parliament and of the Council ([^E0015]);

• (b) the study summaries included in the technical dossier; and

• (c) the safety data sheet as referred to in Article 31 of Regulation (EC) No 1907/2006.

All other available information shall be submitted.

7.7.   Supplementary studies for combinations of plant protection products

Where the plant protection product label indicates the use of the plant protection product with other plant protection products and/or with adjuvants as a tank mix, the studies as referred to under points 7.3.1 to 7.3.6 shall be carried out for the relevant combination of plant protection products. Decisions as to the need for supplementary studies shall 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 plant protection products concerned and available information or practical experience with the plant protection products concerned or similar plant protection products.

The need to perform supplementary studies on the plant protection product shall be based on expert judgement case-by-case, in the light of the particular parameters to be investigated and the objectives to be achieved (for example, for plant protection products containing active substances or other components suspected to have synergistic or additive toxicological effects).

8. RESIDUES IN OR ON TREATED PRODUCTS, FOOD AND FEED

Data and information on residues in or on treated products, food and feed in accordance with Section 6 of Part B of the Annex to Regulation (EU) No 283/2013 shall be submitted, unless the applicant shows that the data and information already submitted for the active substance are sufficient to permit a risk assessment to be performed on the plant protection product.

9. FATE AND BEHAVIOUR IN THE ENVIRONMENT

Data and information in accordance with Section 7 of Part B of the Annex to Regulation (EU) No 283/2013 shall be submitted on the fate and behaviour of the plant protection product in the environment, unless the applicant shows that the data and information already submitted for the active substance are sufficient to permit a risk assessment to be performed on the plant protection product.

10. EFFECTS ON NON-TARGET ORGANISMS

Introduction

• (i) The information provided, taken together with that for the active substance that is a micro-organism provided in accordance with Part B of the Annex to Regulation (EU) No 283/2013 (including possible metabolite(s) of concern as identified in accordance with point 2.8 of Part B of the Annex to Regulation (EU) No 283/2013) shall be sufficient to permit an assessment of the potential impact on non-target species of the plant protection product, when used as proposed. When submitting this information, the applicant shall take into account that the impact on non-target species can result from single, prolonged or repeated exposure and can be reversible or irreversible.

• (ii) Where exposure data are necessary to decide whether a study shall be performed, the data obtained in accordance with Section 9 shall be used. For the estimation of exposure of organisms all relevant information on the plant protection product and on the micro-organism shall be taken into account. Where relevant, the data provided for under this Section shall be used. Where it appears from available data that the plant protection product has a stronger effect than the active substance that is a micro-organism, the data on effects on non-target organisms of the plant protection product shall be used for the calculation of relevant effect/exposure ratios.

• (iii) Unless it can be justified that an assessment of effects on non-target organisms can be performed with the information already available, experimental data may be required. The duration of experimental studies shall be long enough to permit time for incubation, infection and manifestation of adverse effects in non-target organisms, but in line with the expected exposure under the proposed use. In order to distinguish between pathogenic and toxic effects, appropriate controls shall be used in addition to the no-dosed control group, such as inactivated controls and/or sterile filtrate/supernatant controls. Special attention shall be required when the plant protection product contains a micro-organism which is pathogenic to non-target organisms other than mammals and that was not isolated from a relevant European environment. The information provided shall be sufficient to assess environmental impacts.

• (iv) The relevance of non-target organism species used for testing environmental effects shall be based on a weight of evidence approach, taking into consideration, for instance:
• — information on the micro-organism (particularly on biological properties) as required in Part B of the Annex to Regulation (EU) No 283/2013,
• — information concerning the co-formulants, safeners and synergists, as required in Sections 1 to 9, and
• — proposed use patterns of the plant protection product (e.g. foliar or soil application). In order to facilitate the assessment of the significance of test results obtained, where possible, the same strain of each relevant species of non-target organisms shall be used in the various specified tests for effects on non-target organisms.

• (v) All the adverse effects observed in tests and trials performed with the plant protection product shall be reported, and additional studies, which may be necessary to investigate the mechanisms involved and assess the significance of these effects, shall be undertaken and reported.

• (vi) Where adverse toxic effects are indicated in the studies considered for the risk assessment and risk identified may be considered not acceptable, additional toxicity studies under field conditions and in accordance with the proposed recommendations for use shall be conducted, if applicable. The type of study to be performed depends on the effects and the affected non-target organism(s) observed in the studies required in points 10.1 to 10.7 and during efficacy testing and may have to include also further studies on additional non-target species (i.e. different than those initially tested). Special attention shall be given to possible effects on non-target organisms occurring in the relevant European environment and deliberately released organisms for biological control purposes.

• (vii) The information provided for the plant protection product, together with other relevant information, and that provided for the micro-organism (including possible metabolites of concern as identified in point 2.8 of Part B of the Annex to Regulation (EU) No 283/2013) shall be sufficient to:
• — specify the hazard symbols, the indications of danger and relevant risk and safety phrases or the pictograms, signal words, relevant hazard and precautionary statements for the protection of the environment to be mentioned on packaging (containers),
• — permit an evaluation of the short- and long-term risks for non-target species – populations, communities, and processes as appropriate,
• — permit an evaluation whether special precautions are necessary for the protection of non-target species.

10.1.   Effects on terrestrial vertebrates

The same information submitted on the micro-organism (and/or on a plant protection product containing that active substance with respect to a representative use), as detailed in points 8.1, 8.7 and 8.8 of Part B of the Annex to Regulation (EU) No 283/2013 shall be provided for the plant protection product subject of the application, unless the applicant can:

• — justify the applicability and relevance of the outcome of the assessment made on the same data submitted for the micro-organism approval (and/or for a plant protection product containing that active substance with respect to a representative use),

• — predict the effects of the plant protection product on the basis of the data available for the co-formulants (e.g. qualitative and quantitative composition), as well as for the micro-organism and possible metabolites of concern (based on data submitted in accordance with Section 8 of Part B of the Annex to Regulation (EU) No 283/2013 for the approval of the micro-organism(s) in the plant protection product), or

• — justify that the non-target terrestrial vertebrates (e.g. mammals, birds, reptiles, and amphibians) will not be exposed to the plant protection product (based on data submitted in accordance with Section 9).

If generation of data is required based on the provisions laid down under this point, relevant studies shall be performed and they shall provide LD50 values and include gross pathological findings. The studies may be conducted on the species used in the studies referred to in point 8.1 of Part B of the Annex to Regulation (EU) No 283/2013.

10.2.   Effects on aquatic organisms

10.2.1.   Effects on fish

The same information submitted on the micro-organism (and/or on a plant protection product containing that active substance with respect to a representative use) as detailed in points 8.2.1, 8.7 and 8.8 of Part B of the Annex to Regulation (EU) No 283/2013 shall be provided for the plant protection product subject of the application, unless the applicant can:

• — justify the applicability and relevance of the outcome of the assessment made on the same data submitted for the micro-organism approval (and/or on a plant protection product containing that active substance with respect to a representative use),

• — predict the effects of the plant protection product on the basis of the data available for the co-formulants (e.g. qualitative and quantitative composition), as well as for the micro-organism and possible metabolites of concern (based on data submitted in accordance with Section 8 of Part B of the Annex to Regulation (EU) No 283/2013 for the approval of the active substance(s) in the plant protection product), or

• — justify that fish will not be exposed to the components of the plant protection product (based on data submitted in accordance with Section 9).

If generation of data is required based on the provisions laid down under this point, relevant studies shall be performed and they shall provide LD50 values, and shall include gross pathological findings. The studies may be conducted on the species used in the studies referred to in point 8.2.1 of Part B of the Annex to Regulation (EU) No 283/2013.

10.2.2.   Effects on aquatic invertebrates

The same information submitted on the micro-organism (and/or on a plant protection product containing that active substance with respect to a representative use)as detailed in points 8.2.2, 8.7 and 8.8 of Part B of the Annex to Regulation (EU) No 283/2013 shall be provided for the plant protection product subject of the application, unless the applicant can:

• — justify the applicability and relevance of the outcome of the assessment made on the same data submitted for the micro-organism approval (and/or on a plant protection product containing that active substance with respect to a representative use),

• — predict the effects of the plant protection product on the basis of the data available for the co-formulants (e.g. qualitative and quantitative composition), as well as for the micro-organism and possible metabolites of concern (based on data submitted in accordance with Section 8 of Part B of the Annex to Regulation (EU) No 283/2013 for the approval of the active substance(s) in the plant protection product), or

• — justify that the aquatic invertebrates will not be exposed to the components of the plant protection product (based on data submitted in accordance with Section 9).

If generation of data is required based on the provisions laid down under this point, relevant studies shall be performed.

10.2.3.   Effects on algae

The same information submitted on the micro-organism (and/or on a plant protection product containing that active substance with respect to a representative use) as detailed in points 8.2.3, 8.7 and 8.8 of Part B of the Annex to Regulation (EU) No 283/2013 shall be provided for the plant protection product subject of the application, unless the applicant can:

• — justify the applicability and relevance of the outcome of the assessment made on the same data submitted for the micro-organism approval (and/or on a plant protection product containing that active substance with respect to a representative use),

• — predict the effects of the plant protection product on the basis of the data available for the co-formulants (e.g. qualitative and quantitative composition), as well as for the micro-organism and possible metabolites of concern (based on data submitted in accordance with Section 8 of Part B of the Annex to Regulation (EU) No 283/2013 for the approval of the micro-organism(s) in the plant protection product), or

• — justify that algae will not be exposed to the components of the plant protection product (based on data submitted in accordance with Section 9).

If generation of data is required based on the provisions laid down under this point, relevant studies shall be performed.

10.2.4.   Effects on aquatic macrophytes

The same information submitted on the micro-organism (and/or on a plant protection product containing that active substance with respect to a representative use) as detailed in points 8.2.4, 8.7 and 8.8 of Part B of the Annex to Regulation (EU) No 283/2013 shall be provided for the plant protection product subject of the application, unless the applicant can:

• — justify the applicability and relevance of the outcome of the assessment made on the same data submitted for the micro-organism approval (and/or on a plant protection product containing that active substance with respect to a representative use),

• — predict the effects of the plant protection product on the basis of the data available for the co-formulants (e.g. qualitative and quantitative composition), as well as for the micro-organism and possible metabolites of concern (based on data submitted in accordance with in Section 8 of Part B of the Annex to Regulation (EU) No 283/2013 for the approval of the micro-organism(s) in the plant protection product), or

• — justify that aquatic macrophytes will not be exposed to the components of the plant protection product (based on data submitted in accordance with Section 9).

If generation of data is required based on the provisions laid down under this point, relevant studies shall be performed.

10.3.   Effects on bees

The same information submitted on the micro-organism (and/or on a plant protection product containing that active substance with respect to a representative use) as detailed in points 8.3, 8.7 and 8.8 of Part B of the Annex to Regulation (EU) No 283/2013 shall be provided for the plant protection product subject of the application, unless the applicant can:

• — justify the applicability and relevance of the outcome of the assessment made on the same data submitted for the micro-organism approval (and/or on a plant protection product containing that active substance with respect to a representative use),

• — predict the effects of the plant protection product on the basis of the data available for the co-formulants (e.g. qualitative and quantitative composition), as well as for the micro-organism and possible metabolites of concern (based on data submitted in accordance with Section 8 of Part B of the Annex to Regulation (EU) No 283/2013 for the approval of the micro-organism(s) in the plant protection product), or

• — justify that bees will not be exposed to the components of the plant protection product (based on data submitted in accordance with Section 9).

If generation of data is required based on the provisions laid down under this point, relevant studies shall be performed.

10.4.   Effects on non-target arthropods other than bees

The same information submitted on the micro-organism (and/or on a plant protection product containing that active substance with respect to a representative use) as detailed in points 8.4, 8.7 and 8.8 of Part B of the Annex to Regulation (EU) No 283/2013 shall be provided for the plant protection product subject of the application, unless the applicant can:

• — justify the applicability and relevance of the outcome of the assessment made on the same data submitted for the micro-organism approval (and/or on a plant protection product containing that active substance with respect to a representative use),

• — predict the effects of the plant protection product on the basis of the data available for the co-formulants (e.g. qualitative and quantitative composition), as well as for the micro-organism and possible metabolites of concern (based on data submitted in accordance with Section 8 of Part B of the Annex to Regulation (EU) No 283/2013 for the approval of the micro-organism(s) in the plant protection product), or

• — justify that the non-target arthropods other than bees will not be exposed to the components of the plant protection product (based on data submitted in accordance with Section 9).

If generation of data is required based on the provisions laid down under this point, relevant studies shall be performed. Analyses might include further studies on additional species, or higher tier studies such as studies on selected non-target organisms using the formulated plant protection product. The choice of non-target arthropods test species playing an important role in integrated pest management may be based on several factors, such as biological properties of the micro-organism and the intended use (e.g. crop type).

10.5.   Effects on non-target meso- and macroorganisms in soil

The same information submitted on the micro-organism (and/or on a plant protection product containing that active substance with respect to a representative use) as detailed in points 8.5, 8.7 and 8.8 of Part B of the Annex to Regulation (EU) No 283/2013 shall be provided for the plant protection product subject of the application, unless the applicant can:

• — justify the applicability and relevance of the outcome of the assessment made on the same data submitted for the micro-organism approval (and/or on a plant protection product containing that active substance with respect to a representative use),

• — predict the effects of the plant protection product on the basis of the data available for the co-formulants (e.g. qualitative and quantitative composition), as well as for the micro-organism and possible metabolites of concern (based on data submitted in accordance with Section 8 of Part B of the Annex to Regulation (EU) No 283/2013 for the approval of the micro-organism(s) in the plant protection product), or

• — justify that the non-target meso- and macroorganisms in soil will not be exposed to the components of the plant protection product (based on data submitted in accordance with Section 9).

If generation of data is required based on the provisions laid down under this point, relevant studies shall be performed.

10.6.   Effects on non-target terrestrial plants

The same information submitted on the micro-organism (and/or on a plant protection product containing that active substance with respect to a representative use) as detailed in points 8.6, 8.7 and 8.8 of Part B of the Annex to Regulation (EU) No 283/2013 shall be provided for the plant protection product subject of the application, unless the applicant can:

• — justify the applicability and relevance of the outcome of the assessment made on the same data submitted for the micro-organism approval (and/or on a plant protection product containing that active substance with respect to a representative use),

• — predict the effects of the plant protection product on the basis of the data available for the co-formulants (e.g. qualitative and quantitative composition), as well as for the micro-organism and possible metabolites of concern (based on data submitted in accordance with Section 8 of Part B of the Annex to Regulation (EU) No 283/2013 for the approval of the micro-organism(s) in the plant protection product), or

• — justify that the non-target terrestrial plants will not be exposed to the components of the plant protection product (based on data submitted in accordance with Section 9).

If generation of data is required based on the provisions laid down under this point, relevant studies shall be performed.

10.7.   Additional toxicity studies

Further data may be submitted or additional toxicity studies performed, if tests required in points 10.1 to 10.6 have shown adverse effects in one or more non-target organisms and the risk is considered not acceptable. The type of study to be performed shall be chosen based on the effects and the affected non-target organism(s) observed in the studies required in points 10.1 to 10.6 and during efficacy testing, and may have to include also further studies on additional non-target species.

[^E0001]: OJ L 322, 8.12.2010, p. 10.

[^E0002]: Directive 2010/63/EU of the European Parliament and of the Council of 22 September 2010 on the protection of animals used for scientific purposes (OJ L 276, 20.10.2010, p. 33).

[^E0003]: Regulation (EC) No 1272/2008 of the European Parliament and of the Council of 16 December 2008 on classification, labelling and packaging of substances and mixtures, amending and repealing Directives 67/548/EEC and 1999/45/EC, and amending Regulation (EC) No 1907/2006 (OJ L 353, 31.12.2008, p. 1).

[^E0004]: Commission Regulation (EU) No 283/2013 of 1 March 2013 setting out the data requirements for active substances, in accordance with Regulation (EC) No 1107/2009 of the European Parliament and of the Council concerning the placing of plant protection products on the market (OJ L 93, 3.4.2013, p. 1).

[^E0005]: Directive 2004/10/EC of the European Parliament and of the Council of 11 February 2004 on the harmonisation of laws, regulations and administrative provisions relating to the application of the principles of good laboratory practice and the verification of their applications for tests on chemical substances (OJ L 50, 20.2.2004, p. 44).

[^E0006]: OJ L 396, 30.12.2006, p. 1.

[^E0007]: United Nations New York and Geneva (2009) Publication ISBN 978-92-1-139135-0.

[^E0008]: OJ L 365, 31.12.1994, p. 34.

[^E0009]: LD50, abbreviation for ‘Lethal Dose, 50 %’, that is to say the dose required to kill half the members of a tested population after a specified test duration.

[^E0010]: LR50, abbreviation for ‘Lethal Rate, 50 %’, that is to say the application rate required to kill half the members of a tested population after a specified test duration.

[^E0011]: ER50, abbreviation for ‘Effect Rate, 50 %’, that is to say the application rate required to cause an effect on half the members of a tested population after a specified test duration.

[^E0012]: Commission Delegated Regulation (EU) 2021/1760 of 26 May 2021 supplementing Regulation (EU) 2019/6 of the European Parliament and of the Council by establishing the criteria for the designation of antimicrobials to be reserved for the treatment of certain infections in humans (OJ L 353, 6.10.2021, p. 1).

[^E0013]: Regulation (EU) 2019/6 of the European Parliament and of the Council of 11 December 2018 on veterinary medicinal products and repealing Directive 2001/82/EC (OJ L 4, 7.1.2019, p. 43).

[^E0015]: Regulation (EC) No 1907/2006 of the European Parliament and of the Council of 18 December 2006 concerning the Registration, Evaluation, Authorisation and Restriction of Chemicals (REACH), establishing a European Chemicals Agency, amending Directive 1999/45/EC and repealing Council Regulation (EEC) No 793/93 and Commission Regulation (EC) No 1488/94 as well as Council Directive 76/769/EEC and Commission Directives 91/155/EEC, 93/67/EEC, 93/105/EC and 2000/21/EC (OJ L 396, 30.12.2006, p. 1).