Editor’s Highlight: Transplacental and Lactational Transfer of Firemaster® 550 Components in Dosed Wistar Rats

Abstract

FiremasterV R 550 (FM 550) is a commercial mixture of organophosphate and brominated flame retardants currently in use as a replacement for pentaBDE. Its organophosphate components include triphenyl phosphate (TPHP) and a suite of isopropylated triarylphosphate isomers (ITPs); its brominated components include 2-ethylhexyl-2,3,4,5-tetrabromobenzoate (EH-TBB) and bis (2-ethylhexyl)-2,3,4,5-tetrabromophthalate (BEH-TEBP). Taken together, these chemicals have been shown to be endocrine disrupting and potentially toxic, and human exposure to them is widespread. In this study, maternal transfer of FM 550 components, and in some cases their metabolites, was investigated in dosed Wistar rats. Gestational and lactational transfer were examined separately, with dams orally exposed to 300 or 1000 mg of FM 550 for 10 consecutive days during gestation (gestational day [GD] 9-18) or lactation (postnatal day [PND] 3-12). Levels of parent compounds were measured in fetus and whole pup tissue homogenates, and in dam and pup serum, and several metabolites were measured in dam and pup urine. EH-TBB body burdens resulting from lactational transfer were approximately 200-to 300-fold higher than those resulting from placental transfer, whereas low levels of BEH-TEBP were transferred during both lactation and gestation. TPHP and ITPs were rapidly metabolized by the dams and were not detected in whole tissue homogenates. However, diphenyl phosphate (DPHP) and mono-isopropylphenyl phenyl phosphate (ip-PPP) were detected in urine from the dosed animals. This study is the first to confirm ip-PPP as a urinary metabolite of ITPs and establish a pharmacokinetic profile of FM 550 in a mammalian model.

Gestational triphenyl phosphate exposure in C57Bl/6 mice perturbs expression of insulin‐like growth factor signaling genes in maternal and fetal liver

“…Little is known about how and in what form TPhP crosses the placenta, therefore it is possible that differences lie in exposure levels to these active metabolites and the parent compound between the maternal and fetal compartments. A recent study conducted by Phillips et al (Phillips et al, ) did not detect any gestational transfer of TPhP following in utero exposure to Firemaster 550 in rats but did detect its metabolite DPhP in maternal urine. Thus, the difference in response to TPhP could also be due to different internal concentrations of TPhP reaching the maternal and fetal livers.…”

Sex Specific Placental Accumulation and Behavioral Effects of Developmental Firemaster 550 Exposure in Wistar Rats

“…Dams were not dosed by individual weight but rather by the average weight of the females before they were impregnated (300 g), producing exposures of approximately 0, 1 and 3.3 mg/kg bw per day FM 550. Additional methodological details regarding dosing and internal FM 550 exposure levels were published in a prior study using the same animals 29 .…”

“…We have recently shown that the brominated components can be placentally transferred in rats, with detectable levels in homogenized fetal tissue from dams exposed to 1000 μg FM 550 over 10 days 29 , demonstrating the potential for fetal brain exposure. It has subsequently been shown that PBDEs sex-specifically bioaccumulate in human placenta 30 suggesting the potential for sexually dimorphic placental FR exposures.…”

Developmental Exposure to the Flame Retardant Mixture Firemaster 550 Compromises Adult Bone Integrity in Male but not Female Rats

“…Work by us and others have identified this mixture to be developmentally neurotoxic, endocrine disrupting, and obesogenic [5][6][7][8][9][10][11][12][13]. Human exposure is nearly ubiquitous with both gestational and lactational transfer as significant exposure routes in addition to direct exposure via household dust, which is inadvertently ingested or inhaled [14][15][16][17]. Additionally, the individual components are present in other FR mixtures, and many other commonly used products.…”