标题：Rodent Thyroid, Liver, and Fetal Testis Toxicity of the Monoester Metabolite of Bis-(2-ethylhexyl) Tetrabromophthalate (TBPH), a Novel Brominated Flame Retardant Present in Indoor Dust
摘要：a c k g r o u n d: Bis-(2-ethylhexyl) tetrabromophthalate (TBPH) is widely used as a replacement for polybrominated diphenyl ethers (PBDEs) in commercial flame retardant mixtures such as Firemaster 550. It is also used in a commercial mixture called DP 45. Mono-(2-ethyhexyl) tetra-bromo phthalate (TBMEHP) is a potentially toxic metabolite.oB j e c t i v e s: We used in vitro and rodent in vivo models to evaluate human exposure and the poten-tial metabolism and toxicity of TBPH. Me t h o d s: Dust collected from homes, offices, and cars was measured for TBPH by gas chroma-tography followed by mass spectrometry. Pregnant rats were ga vaged with TBME HP (200 or 500 mg/kg) or corn oil on gestational days 18 and 19, and dams and fetuses were evaluated histologically for toxicity. We also assessed TBMEHP for deiodinase inhibition using rat liver microsomes and for peroxisome proliferator-activated receptor (PPAR) αand γactiva tion using murine FAO cells and NIH 3T3 L1 cells. re s u l t s: TBPH concentrations in dust from office buildings (median, 410 ng/g) were higher than in main living areas in homes (median, 150 ng/g). TBPH was metabolized by purified porcine esterases to TBMEHP. Two days of TBMEHP exposure in the rat produced maternal hypothyroid-ism with markedly decreased serum T3 (3,3′,5-triiodo-l-thyronine), maternal hepatotoxicity, and increased multi nucleated germ cells (MNGs) in fetal testes without anti androgenic effects. In vitro, TBMEHP inhibited deiodinase activity, induced adipocyte differentiation in NIH 3T3 L1 cells, and activated PPARα- and PPARγ-mediated gene transcription in NIH 3T3 L1 cells and FAO cells, respectively.co n c l u s i o n s: TBPH a) is present in dust from indoor environments (implying human exposure) and b) can be metabolized by porcine esterases to TBMEHP, which c) elicited maternal thyro-toxic and hepatotoxic effects and d) induced MNGs in the fetal testes in a rat model. In mouse NIH 3T3 L1 pre adipocyte cells, TBMEHP inhibited rat hepatic microsome deiodinase activity and was an agonist for PPARs in murine FAO and NIH 3T3 L1 cells
