Grouping of endocrine disrupting chemicals for mixture risk assessment - Evidence from a rat study.
Autor: | Christiansen S; Division of Diet, Disease Prevention and Toxicology, National Food Institute, Technical University of Denmark, Kemitorvet Building 202, Kgs. Lyngby DK-2800, Denmark. Electronic address: sochr@food.dtu.dk., Axelstad M; Division of Diet, Disease Prevention and Toxicology, National Food Institute, Technical University of Denmark, Kemitorvet Building 202, Kgs. Lyngby DK-2800, Denmark., Scholze M; Institute of Environment, Health and Societies, Brunel University London, Quad North, Kingston Lane, Uxbridge UB8 3PH, UK., Johansson HKL; Division of Diet, Disease Prevention and Toxicology, National Food Institute, Technical University of Denmark, Kemitorvet Building 202, Kgs. Lyngby DK-2800, Denmark., Hass U; Division of Diet, Disease Prevention and Toxicology, National Food Institute, Technical University of Denmark, Kemitorvet Building 202, Kgs. Lyngby DK-2800, Denmark., Mandrup K; Division of Diet, Disease Prevention and Toxicology, National Food Institute, Technical University of Denmark, Kemitorvet Building 202, Kgs. Lyngby DK-2800, Denmark., Frandsen HL; Research Group for Analytical Food Chemistry, National Food Institute, Technical University of Denmark, Kemitorvet Building 202, DK-2800 Kgs. Lyngby, Denmark., Frederiksen H; Department of Growth and Reproduction, Rigshospitalet, University of Copenhagen, Copenhagen, Denmark., Isling LK; Division of Diet, Disease Prevention and Toxicology, National Food Institute, Technical University of Denmark, Kemitorvet Building 202, Kgs. Lyngby DK-2800, Denmark., Boberg J; Division of Diet, Disease Prevention and Toxicology, National Food Institute, Technical University of Denmark, Kemitorvet Building 202, Kgs. Lyngby DK-2800, Denmark. |
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Jazyk: | angličtina |
Zdroj: | Environment international [Environ Int] 2020 Sep; Vol. 142, pp. 105870. Date of Electronic Publication: 2020 Jun 24. |
DOI: | 10.1016/j.envint.2020.105870 |
Abstrakt: | Exposure to mixtures of endocrine disrupting chemicals may contribute to the rising incidence of hormone-related diseases in humans. Real-life mixtures are complex, comprised of chemicals with mixed modes of action, and essential knowledge is often lacking on how to group such chemicals into cumulative assessment groups, which is an essential prerequisite to conduct a chemical mixture risk assessment. We investigated if mixtures of chemicals with diverse endocrine modes of action can cause mixture effects on hormone sensitive endpoints in developing and adult rat offspring after perinatal exposure. Wistar rats were exposed during pregnancy and lactation simultaneously to either bisphenol A and butylparaben (Emix), diethylhexyl phthalate and procymidone (Amix), or a mixture of all four substances (Totalmix). In male offspring, the anogenital distance was significantly reduced and nipple retention increased in animals exposed to Amix and Totalmix, and the mixture effects were well approximated by the dose addition model. The combination of Amix and Emix responded with more marked changes on these and other endocrine-sensitive endpoints than each binary mixture on its own. Sperm counts were reduced by all exposures. These experimental outcomes suggest that the grouping of chemicals for mixture risk assessment should be based on common health outcomes rather than only similar modes or mechanisms of action. Mechanistic-based approaches such as the concept of Adverse Outcome Pathway (AOP) can provide important guidance if both the information on shared target tissues and the information on shared mode/mechanism of action are taken into account. Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper. (Copyright © 2020 The Authors. Published by Elsevier Ltd.. All rights reserved.) |
Databáze: | MEDLINE |
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