Non-monotonic dose-response relationships and endocrine disruptors: a qualitative method of assessment

Environmental Health

Review

Claude Emond¹  Scott M Belcher²  Luc P Belzunces³  Claire Beausoleil⁴  Fabien Lagarde⁴  Christophe Rousselle⁴  Michel Guerbet⁵ 

[1] BioSimulation Consulting Inc., Newark, DE, USA;Department of Pharmacology and Cell Biophysics, University of Cincinnati, College of Medicine, Cincinnati, OH, USA;INRA, Laboratoire de Toxicologie Environnementale, UR 406 A&E, CS 40509, 84914, Avignon Cedex 9, France;Risk Assessment Department, French Agency for Food, Environmental and Occupational Health & Safety (ANSES), 14 rue Pierre et Marie Curie, 94701, Maisons-Alfort Cedex, France;Université de Rouen, UFR Médecine Pharmacie, Laboratoire de Toxicologie, UR 4651 ABTE, 76183, Rouen Cedex 1, France;

关键词: Endocrine disruptors;    NMDR;    Non-monotonic;    Dose-response;    Risk assessment;    Bisphenol A;   

DOI  :  10.1186/1476-069X-14-13

 received in 2014-10-14, accepted in 2015-01-16,  发布年份 2015

来源: Springer

【 摘 要 】

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.

【 授权许可】

Unknown   
© Lagarde et al.; licensee BioMed Central. 2015. This article is published under license to BioMed Central Ltd. This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/4.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly credited. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated.