A testing strategy for the identification of mammalian, systemic endocrine disruptors with particular focus on steroids.

Regulatory Toxicology and Pharmacology : RTP
S N KolleB van Ravenzwaay

Abstract

Most endocrine disruptors interact with hormone receptors or steroid biosynthesis and metabolism, thereby modifying the physiological function of endogenous hormones. Here, we present an alternative testing paradigm for detection of endocrine modes of action that replace and reduce animal testing through refinement. Receptor mediated endocrine effects were assessed using the yeast-based receptor-mediated transcriptional activation YES/YAS assays and effects on steroid hormone biosynthesis were assessed using the human cell line H295R in the steroidogenesis assay. In our testing paradigm we propose to complement the in vitro assays with a single in vivo repeated dose study in which plasma samples are analyzed for their metabolome profile in addition to classical parameters such as histopathology. The combination of these methods does not only contribute to refinement and reduction of animal testing, but also has significantly increased the efficient allocation of resources and allows for a sound assessment of the endocrine disruption potential of compounds. Thus, this proposal constitutes a potentially attractive alternative to EPA's Endocrine Disruptor Screening Program to identify mammalian, systemic endocrine modes of action....Continue Reading

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Citations

Nov 28, 2015·Molecules : a Journal of Synthetic Chemistry and Natural Product Chemistry·Magdalena GajęckaMaciej Gajęcki
Jun 27, 2015·Environment International·Matthew P DentFrancis L Martin
Oct 12, 2013·Journal of Applied Toxicology : JAT·Si WangToine F H Bovee
Jan 24, 2015·Critical Reviews in Toxicology·David RouquiéChrista Hennes
Jul 16, 2014·Regulatory Toxicology and Pharmacology : RTP·Tzutzuy RamirezBennard van Ravenzwaay
Apr 25, 2017·Environmental Sciences Europe·Sarah E CrawfordHarald F Krug

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