Journal article
Grouping of endocrine disrupting chemicals for mixture risk assessment - Evidence from a rat study
Research Group for Molecular and Reproductive Toxicology, National Food Institute, Technical University of Denmark1
National Food Institute, Technical University of Denmark2
Brunel University London3
Research Group for Analytical Food Chemistry, National Food Institute, Technical University of Denmark4
University of Copenhagen5
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.
Language: | English |
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Publisher: | Elsevier |
Year: | 2020 |
Pages: | 105870 |
ISSN: | 18736750 and 01604120 |
Types: | Journal article |
DOI: | 10.1016/j.envint.2020.105870 |
ORCIDs: | Christiansen, Sofie , Axelstad, Marta Axelstad , Johansson, Hanna Katarina Lilith , Hass, Ulla , Mandrup, Karen Mandrup , Frandsen, Henrik Lauritz and Boberg, Julie |