Human exposure to synthetic endocrine disrupting chemicals (S-EDCs) is generally negligible as compared to natural compounds with higher or comparable endocrine activity: how to evaluate the risk of the S-EDCs?
-
Published:2020-06-08
Issue:7
Volume:94
Page:2549-2557
-
ISSN:0340-5761
-
Container-title:Archives of Toxicology
-
language:en
-
Short-container-title:Arch Toxicol
Author:
Autrup Herman,Barile Frank A.,Berry Sir Colin,Blaauboer Bas J.,Boobis Alan,Bolt Herrmann,Borgert Christopher J.,Dekant Wolfgang,Dietrich Daniel,Domingo Jose L.,Gori Gio Batta,Greim Helmut,Hengstler Jan,Kacew Sam,Marquardt Hans,Pelkonen Olavi,Savolainen Kai,Heslop-Harrison Pat,Vermeulen Nico P.
Abstract
AbstractTheoretically, both synthetic endocrine disrupting chemicals (S-EDCs) and natural (exogenous and endogenous) endocrine disrupting chemicals (N-EDCs) can interact with endocrine receptors and disturb hormonal balance. However, compared to endogenous hormones, S-EDCs are only weak partial agonists with receptor affinities several orders of magnitude lower. Thus, to elicit observable effects, S-EDCs require considerably higher concentrations to attain sufficient receptor occupancy or to displace natural hormones and other endogenous ligands. Significant exposures to exogenous N-EDCs may result from ingestion of foods such as soy-based diets, green tea and sweet mustard. While their potencies are lower as compared to natural endogenous hormones, they usually are considerably more potent than S-EDCs. Effects of exogenous N-EDCs on the endocrine system were observed at high dietary intakes. A causal relation between their mechanism of action and these effects is established and biologically plausible. In contrast, the assumption that the much lower human exposures to S-EDCs may induce observable endocrine effects is not plausible. Hence, it is not surprising that epidemiological studies searching for an association between S-EDC exposure and health effects have failed. Regarding testing for potential endocrine effects, a scientifically justified screen should use in vitro tests to compare potencies of S-EDCs with those of reference N-EDCs. When the potency of the S-EDC is similar or smaller than that of the N-EDC, further testing in laboratory animals and regulatory consequences are not warranted.
Publisher
Springer Science and Business Media LLC
Subject
Health, Toxicology and Mutagenesis,Toxicology,General Medicine
Reference45 articles.
1. Adler S, Basketter D, Creton S, Pelkonen O, van Benthem J et al (2011) Alternative (non-animal) methods for cosmetics testing: current status and future
prospects-2010. Arch Toxicol 85(5):367–485 2. Autrup H, Barile FA, Blaauboer BJ, Degen GH, Dekant W, Dietrich D, Domingo JL, Gori GB, Greim H, Hengstler JG, Kacew S, Marquardt H, Pelkonen O, Savolainen K, Vermeulen NP (2015) Principles of pharmacology and toxicology also govern effects of chemicals on the endocrine system. Toxicol Sci 146:11–15 3. Autrup H, Barile FA, Blaauboer BJ, Degen GH, Dekant W, Dietrich D, Domingo JL, Gori GB, Greim H, Hengstler JG, Kacew S, Marquardt H, Pelkonen O, Savolainen K, Vermeulen NP (2016a) Response to “the path forward on endocrine disruptors requires focus” by Zoeller, et al. Toxicol Sci 149:273–274 4. Autrup HN, Berry SC, Cohen SM, Creppy EE, de Camargo JL, Dekant W, Dietrich D, Galli CL, Goodman JI, Gori GB, Greim HA, Klaunig JE, Lotti M, Marquardt HW, Wallace KB, Yamazaki H (2016b) Whither the impending European regulation of presumed endocrine disruptors? Regul Toxicol Pharmacol 82:A1–A2 5. Bolt HM, Janning P, Michna H, Degen GH (2001) Comparative assessment of endocrine modulators with oestrogenic activity: I. Definition of a hygiene-based margin of safety (HBMOS) for xeno-oestrogens against the background of European developments. Arch Toxicol 74:649–662
Cited by
15 articles.
订阅此论文施引文献
订阅此论文施引文献,注册后可以免费订阅5篇论文的施引文献,订阅后可以查看论文全部施引文献
|
|