Knudsen Gabriel A, Hall Samantha M, Richards Alicia C, Birnbaum Linda S
NCI Laboratory of Toxicology and Toxicokinetics, Research Triangle Park, NC, USA.
NCI Laboratory of Toxicology and Toxicokinetics, Research Triangle Park, NC, USA.
Chemosphere. 2018 Feb;192:5-13. doi: 10.1016/j.chemosphere.2017.10.122. Epub 2017 Oct 28.
Tetrabromobisphenol-A (TBBPA) is a brominated flame retardant (BFR) commonly used in electronics to meet fire safety standards and has the largest worldwide production of any BFR. TBBPA has been detected in human breast milk and maternal/cord serum, indicating exposure to mothers, fetuses, and breastfeeding newborns although exposure to fetuses and newborns is poorly understood. Pregnant or nursing Wistar Han IGS rats were administered [C]-TBBPA in a single dose (25 mg/kg, 2.5 μCi/kg) and euthanized between 0.5&24 h post dose to determine disposition in pregnant and nursing rats and their pups. Systemic exposure was largely unchanged between 1&8 h post dose in pregnant rats; [C]-radioactivity in blood varied only slightly between 0.5&8 h (2.6 ± 0.6 → 2.6 ± 0.8 nmol-eq/mL) but was below the limit of detection at 24 h with an absorption half-life of 16min and elimination half-life of 17 h. C was observed at 30min in lactating rats and concentrations fell steadily through 8 h. Plasma from pregnant rats contained a mixture of TBBPA and TBBPA-conjugates at 30min but only metabolites in subsequent samples. TBBPA was not detected in lactating dam plasma in this study. Placental concentrations increased through 8 h while whole-fetus C occurred at 2 h post dose. In lactating animals, liver, uterus, and mammary time-concentration curves lagged slightly behind blood-concentration curves. It was clear from these studies that TBBPA is available to both the developing fetus and nursing pup following maternal exposure, and nursing pups are continuously exposed via contaminated milk produced by their mother. This research was supported in part by the Intramural Research Program of NIH/NCI.
四溴双酚A（TBBPA）是一种溴化阻燃剂（BFR），常用于电子产品以满足消防安全标准，是全球产量最大的溴化阻燃剂。已在人母乳和母体/脐带血清中检测到TBBPA，这表明母亲、胎儿和母乳喂养的新生儿均有接触，但对胎儿和新生儿的接触情况了解甚少。对怀孕或哺乳的Wistar Han IGS大鼠单次给予[C]-TBBPA（25mg/kg，2.5μCi/kg），并在给药后0.5至24小时之间实施安乐死，以确定怀孕和哺乳大鼠及其幼崽体内的药物处置情况。怀孕大鼠给药后1至8小时全身暴露情况基本不变；血液中的[C]-放射性在0.5至8小时之间仅有轻微变化（2.6±0.6→2.6±0.8nmol-eq/mL），但在24小时时低于检测限，吸收半衰期为16分钟，消除半衰期为17小时。在哺乳大鼠中，30分钟时观察到了C，其浓度在8小时内稳步下降。怀孕大鼠血浆在30分钟时含有TBBPA和TBBPA结合物的混合物，但后续样本中仅含有代谢物。在本研究中，未在哺乳母鼠血浆中检测到TBBPA。胎盘浓度在8小时内升高，而全胎C在给药后2小时出现。在泌乳动物中，肝脏、子宫和乳腺的时间-浓度曲线略滞后于血液浓度曲线。从这些研究中可以清楚地看出，母体接触后，发育中的胎儿和哺乳幼崽均可接触到TBBPA，并且哺乳幼崽会通过其母亲分泌的受污染乳汁持续接触。本研究部分得到了美国国立卫生研究院/国立癌症研究所内部研究项目的支持。
