Flame retardant tricresyl phosphate gestational exposure induced endocrine and metabolic disruptions in rat

Organophosphate flame retardants (OPFRs), including tricresyl phosphate (TCP), are incorporated into a wide variety of polymers to give them fire resistance. They are therefore present in numerous industrial and consumer products such as electrical and electronic appliances, building materials, furnishings and textiles. TCP induces disturbed fertility, intracellular lipid accumulation and disrupts fatty acid metabolism. The toxicological profiles of these molecules, combined with the lack of data, led to interest in their effects on male reproductive function and lipid metabolism.

Sprague-Dawley rats were exposed to increasing doses of TCP from days 12 to 19 of gestation, a critical period for reproductive masculinization and genital development. Organs and biological fluid samples were collected from the mother and from the fetus. Maternal physiology, via weight monitoring and blood biochemistry, was analyzed, as were gestation parameters. Fetal testosterone production was measured, with the expression of genes involved in steroidogenesis. Fatty acid profiles in maternal and fetal livers and maternal adrenals were analyzed in association with measurements of the expression of genes involved in cholesterol and fatty acid metabolism.

TCP demonstrated endocrine and metabolic disruption, inducing maternal adverse impact at 300 mg/kg, with reduced weight gain, liver weight and increased adrenal weight. Furthermore, at fetal level, in utero exposure to TCP induced a significant decrease in testosterone production without disruption of steroidogenesis gene expression. TCP exposure disrupted fatty acid profiles in maternal and fetal livers and maternal adrenals. These results shed new light on the toxicological properties of OPFRs following different mechanisms of action.