Earlier this month ECHA and the European Food Safety Authority published the ‘Guidance for the identification of endocrine disruptors in the context of Regulations (EU) No 528/2012 and (EC) No 1107/2007′ (https://www.efsa.europa.eu/en/efsajournal/pub/5311) to implement the scientific criteria for the determination of endocrine-disruption properties in the context of the PPP or BPR Regulations.
Regarding in vivo testing as an information source for endocrine disruptor identification, this guidance document describes not only mammalian but non-mammalian methods and the parameters measured in these relevant to identify endocrine disruption. Parameters such as growth, behaviour, sexual maturity, fecundity and reproduction parameters (fecundity, gonado-somatic index) can be sensitive to substances interfering with the sex hormone system or the thyroid hormone system. However, these parameters are not necessarily ‘EATS (estrogenic, androgenic, thyroidal and steroidogenic)–mediated’ since they can be influenced by other endocrine and non-endocrine factors such as systemic toxicity or dietary influences. In this instance, the guidance document states that they can still be used in a Weight of Evidence (WoE) approach to draw a conclusion on a specific endocrine pathway, but according to the guidance document, parameters measured in non-mammalian in vivo test methods relevant to support the identification of potential endocrine disruptors are vitellogenin and spiggin levels, secondary sex characteristics, sex ratio, gonadosomatic index, gonad histopathology and thyroid histopathology.
For fish, the following in vivo assays are listed in the guidance to investigate potential endocrine adverse effects: fish short-term reproduction assay (OECD TG 229), the 21-day fish assay (OECD TG 230) and its variant the androgenised female stickleback screen (OECD GD 148), fish sexual development test (OECD TG 234), medaka extended one-generation reproduction test (OECD TG 240), fish life cycle toxicity test (OPPTS 850.1500) and fish early life stage toxicity test (OECD TG 210). Additionally, three other tests are currently under validation at the OECD level: the EASZY test, an in vivo fish-based assay designed to quantify the estrogenic effect on fish in early life stages, the juvenile medaka anti-androgen screening assay (JMASA) and the RADAR assay, an in vivo fish-based assay designed to quantify the androgen axis activity in early life stages. For amphibians, two standardised tests; the amphibian metamorphosis assay (OECD TG 231) and the larval amphibian growth and development assay (OECD TG 241) are listed, as well as Xenopus embrionic thryroid signalling assay XETA, currently under validation by the OECD. Lastly, for birds, only two standardised in vivo methods are available; avian reproduction test (OECD TG 206) and US EPA avian two-generation study (OCSPP 890.2100), both offering limited information on effects concerning endocrine disruption.
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