Division 3.6.5

An active substance, safener or synergist shall only be approved if, on the basis of the assessment of F1nationally or internationally agreed test guidelines or other available data and information, including a review of the scientific literature, reviewed by the F2competent authority, it is not considered to have endocrine disrupting properties that may cause adverse effect in humans, unless the exposure of humans to that active substance, safener or synergist in a plant protection product, under realistic proposed conditions of use, is negligible, that is, the product is used in closed systems or in other conditions excluding contact with humans and where residues of the active substance, safener or synergist concerned on food and feed do not exceed the default value set in accordance with point (b) of Article 18(1) of Regulation (EC) No 396/2005.

By 14 December 2013, the Commission shall present to the Standing Committee on the Food Chain and Animal Health a draft of the measures concerning specific scientific criteria for the determination of endocrine disrupting properties to be adopted in accordance with the regulatory procedure with scrutiny referred to in Article 79(4).

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F4From X110 November 2018, an active substance, safener or synergist shall be considered as having endocrine disrupting properties that may cause adverse effect in humans if, based on points (1) to (4) of the sixth paragraph, it is a substance that meets all of the following criteria, unless there is evidence demonstrating that the adverse effects identified are not relevant to humans:

1. (1)

   it shows an adverse effect in an intact organism or its progeny, which is a change in the morphology, physiology, growth, development, reproduction or life span of an organism, system or (sub)population that results in an impairment of functional capacity, an impairment of the capacity to compensate for additional stress or an increase in susceptibility to other influences;

2. (2)

   it has an endocrine mode of action, i.e. it alters the function(s) of the endocrine system;

3. (3)

   the adverse effect is a consequence of the endocrine mode of action.

The identification of an active substance, safener or synergist as having endocrine disrupting properties that may cause adverse effect in humans in accordance with the fifth paragraph shall be based on all of the following points:

1. (1)

   all available relevant scientific data (in vivo studies or adequately validated alternative test systems predictive of adverse effects in humans or animals; as well as in vivo, in vitro, or, if applicable, in silico studies informing about endocrine modes of action):

   1. (a)

      scientific data generated in accordance with internationally agreed study protocols, in particular those listed in F5guidance issued in accordance with this Regulation;

   2. (b)

      other scientific data selected applying a systematic review methodology, in particular following guidance on literature data F6issued, in accordance with this Regulation;

2. (2)

   an assessment of the available relevant scientific data based on a weight of evidence approach in order to establish whether the criteria set out in the fifth paragraph are fulfilled; in applying the weight of evidence determination, the assessment of the scientific evidence shall, in particular, consider all of the following factors:

   1. (a)

      both positive and negative results;

   2. (b)

      the relevance of the study designs, for the assessment of adverse effects and of the endocrine mode of action;

   3. (c)

      the quality and consistency of the data, considering the pattern and coherence of the results within and between studies of a similar design and across different species;

   4. (d)

      the route of exposure, toxicokinetic and metabolism studies;

   5. (e)

      the concept of the limit dose, and international guidelines on maximum recommended doses and for assessing confounding effects of excessive toxicity;

3. (3)

   using a weight of evidence approach, the link between the adverse effect(s) and the endocrine mode of action shall be established based on biological plausibility, which shall be determined in the light of current scientific knowledge and under consideration of internationally agreed guidelines;

4. (4)

   adverse effects that are non-specific secondary consequences of other toxic effects shall not be considered for the identification of the substance as endocrine disruptor.