Endocrine_Editorial_Referenced_2020_AutrupGreimDekantBerryHHeslopHarrison.pdf (254.86 kB)
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?
journal contributionposted on 2020-10-21, 11:42 authored by Herman Autrup, Frank A Barile, Sir Colin Berry, Bas J Blaauboer, Alan Boobis, Herrmann Bolt, Christopher J Borgert, Wolfgang Dekant, Daniel Dietrich, Jose L Domingo, Gio Batta Gori, Helmut Greim, Jan Hengstler, Sam Kacew, Hans Marquardt, Olavi Pelkonen, Kai Savolainen, Pat Heslop-Harrison, Nico P Vermeulen
Theoretically, 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 than S-EDCs. 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.
CitationEnvironmental Toxicology and Pharmacology, Volume 78, August 2020, 103396
Author affiliationDepartment of Genetics and Genome Biology
- AM (Accepted Manuscript)