Valentino S A, Sabaté J-P, Perceau M, Viton S, Grossmann S, Mascherin M, Rousseau-Ralliard D, Ndiaye D, Cosnier F, Gaté L
Institut national de recherche et de sécurité pour la prévention des accidents du travail et des maladies professionnelles (INRS), Dept Toxicologie et Biométrologie, 1 rue du Morvan, 54519 Vandoeuvre-lès-Nancy, France.
Institut national de recherche et de sécurité pour la prévention des accidents du travail et des maladies professionnelles (INRS), Dept Toxicologie et Biométrologie, 1 rue du Morvan, 54519 Vandoeuvre-lès-Nancy, France.
Toxicol Appl Pharmacol. 2025 Oct;503:117493. doi: 10.1016/j.taap.2025.117493. Epub 2025 Jul 29.
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.
有机磷酸酯阻燃剂（OPFRs），包括磷酸三甲苯酯（TCP），被添加到各种各样的聚合物中以赋予它们阻燃性。因此，它们存在于众多工业和消费品中，如电气和电子产品、建筑材料、家具和纺织品。TCP会导致生育能力紊乱、细胞内脂质积累并扰乱脂肪酸代谢。这些分子的毒理学特征，再加上数据的缺乏，引发了人们对其对雄性生殖功能和脂质代谢影响的关注。在妊娠第12天至19天（生殖男性化和生殖器发育的关键时期），将Sprague-Dawley大鼠暴露于剂量递增的TCP中。从母体和胎儿收集器官和生物流体样本。通过体重监测和血液生化分析母体生理学，以及妊娠参数。测量胎儿睾酮的产生，并检测参与类固醇生成的基因的表达。分析母体和胎儿肝脏以及母体肾上腺中的脂肪酸谱，并结合测量参与胆固醇和脂肪酸代谢的基因的表达。TCP表现出内分泌和代谢紊乱，在300mg/kg时对母体产生不良影响，体重增加减少、肝脏重量减轻和肾上腺重量增加。此外，在胎儿水平，子宫内暴露于TCP会导致睾酮产生显著减少，而不会破坏类固醇生成基因的表达。TCP暴露扰乱了母体和胎儿肝脏以及母体肾上腺中的脂肪酸谱。这些结果为OPFRs通过不同作用机制产生的毒理学特性提供了新的线索。
