ESPE Yearbook of Paediatric Endocrinology

J Appl Toxicol. 2021 Apr;41(4):572–586. doi: 10.1002/jat.4066. PMID: 329695

In this study, pregnant dams were exposed to different types of organophosphate flame retardants (OPFRs) at a sensitive development period (from gestation to lactation). The offspring were fed either a high or a low-fat diet for 17 weeks and then underwent a battery of metabolic assessments. OPFR exposure did not alter the weight of the offspring but there were sex dependent changes in metabolic rate, glucose clearance, insulin tolerance, haemodynamics and liver gene expression, potentially via interactions involving steroid and nuclear receptor expression.

Endocrine disrupting compounds (EDC) are exogenous chemicals that interfere with hormone actions and have been implicated in the etiology of metabolic disease with effects on glucose homeostasis, hormone production, haemodynamics and oxygen consumption. One such group of EDCs are flame retardants, including polybrominated diphenyl ethers (PBDEs) and organophosphate flame retardants (OPFRs). PBDEs have been phased out but OPFRs are increasingly being used in household products. OPFRs interact with nuclear and steroid receptors. There is limited information on the effects of maternal OPFR exposure on offspring energy homeostasis in mammalian rodent models. The key steroid hormone receptor in the liver identified in this study was the estrogen receptor (ERα). EDC are known to affect the expression of nuclear receptors (1) so it is likely that exposure to OPFRs affects the activity and expression of ERα and nuclear receptor thus leading to toxicity and providing an explanation for the sex specific changes observed here.

Reference: 1. La Merrill MA, Vandenberg LN, Smith MT, Goodson W, Browne P, Patisaul HB, Guyton KZ, Kortenkamp A, Cogliano VJ, Woodruff TJ, Rieswijk L, Sone H, Korach KS, Gore AC, Zeise L, Zoeller RT. Consensus on the key characteristics of endocrine-disrupting chemicals as a basis for hazard identification 2019. Nature Reviews Endocrinology, 16(January), 45–57.