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Author Lagarde, Fabien ♦ Beausoleil, Claire ♦ Belcher, Scott M. ♦ Belzunces, Luc P. ♦ Emond, Claude ♦ Guerbet, Michel ♦ Rousselle, Christophe
Source Paperity
Content type Text
Publisher BioMed Central
File Format PDF ♦ HTM / HTML
Copyright Year ©2015
Abstract Experimental studies investigating the effects of endocrine disruptors frequently identify potential unconventional dose-response relationships called non-monotonic dose-response (NMDR) relationships. Standardized approaches for investigating NMDR relationships in a risk assessment context are missing. The aim of this work was to develop criteria for assessing the strength of NMDR relationships. A literature search was conducted to identify published studies that report NMDR relationships with endocrine disruptors. Fifty-one experimental studies that investigated various effects associated with endocrine disruption elicited by many substances were selected. Scoring criteria were applied by adaptation of an approach previously used for identification of hormesis-type dose-response relationships. Out of the 148 NMDR relationships analyzed, 82 were categorized with this method as having a “moderate” to “high” level of plausibility for various effects. Numerous modes of action described in the literature can explain such phenomena. NMDR can arise from numerous molecular mechanisms such as opposing effects induced by multiple receptors differing by their affinity, receptor desensitization, negative feedback with increasing dose, or dose-dependent metabolism modulation. A stepwise decision tree was developed as a tool to standardize the analysis of NMDR relationships observed in the literature with the final aim to use these results in a Risk Assessment purpose. This decision tree was finally applied to studies focused on the effects of bisphenol A.
Learning Resource Type Article
Publisher Date 2015-02-11
e-ISSN 1476069X
Journal Environmental Health
Issue Number 14