Phillips Allison L, Chen Albert, Rock Kylie D, Horman Brian, Patisaul Heather B, Stapleton Heather M
*Nicholas School of the Environment, Levine Science Research Center, Duke University, Durham, North Carolina 27710;
Department of Biology, North Carolina State University, Raleigh, North Carolina, 27695.
Toxicol Sci. 2016 Oct;153(2):246-57. doi: 10.1093/toxsci/kfw122. Epub 2016 Jun 30.
Firemaster® 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 µg 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.
Firemaster 550 ;: lactational transfer ;: gestational transfer; metabolites; rodent.
Firemaster® 550(FM 550)是一种有机磷酸酯和溴化阻燃剂的商业混合物,目前用作五溴二苯醚的替代品。其有机磷酸酯成分包括磷酸三苯酯(TPHP)和一组异丙基化三芳基磷酸酯异构体(ITPs);其溴化成分包括2-乙基己基-2,3,4,5-四溴苯甲酸酯(EH-TBB)和双(2-乙基己基)-2,3,4,5-四溴邻苯二甲酸酯(BEH-TEBP)。综合来看,这些化学物质已被证明具有内分泌干扰性且可能有毒,并且人类广泛接触到它们。在本研究中,对经给药的Wistar大鼠中FM 550成分及其某些代谢物的母体转移情况进行了研究。分别检查了孕期和哺乳期的转移情况,在孕期(妊娠第9 - 18天)或哺乳期(出生后第3 - 12天),母鼠连续10天口服300或1000μg的FM 550。在胎儿和全幼崽组织匀浆、母鼠和幼崽血清中测量母体化合物的水平,并在母鼠和幼崽尿液中测量几种代谢物。哺乳期转移导致的EH-TBB体内负荷比胎盘转移导致的高出约200至300倍,而在哺乳期和孕期均有低水平的BEH-TEBP转移。TPHP和ITPs被母鼠迅速代谢,在全组织匀浆中未检测到。然而,在给药动物的尿液中检测到了磷酸二苯酯(DPHP)和单异丙基苯基苯基磷酸酯(ip-PPP)。本研究首次证实ip-PPP是ITPs的尿液代谢物,并在哺乳动物模型中建立了FM 550的药代动力学特征。
Firemaster 550;哺乳期转移;孕期转移;代谢物;啮齿动物