Organophosphate Flame Retardants Exposure Disrupts Serum Lipid Metabolism and Induces Hepatotoxicity: Evidence from the Population and Mouse Model.
TL;DR
TDCIPP exposure induced hepatotoxicity in mice, and may induce hepatic lipid toxicity in mice, indicating that the non-cancer risk of BDCIPP should be of concern.
Abstract
Organophosphate flame retardants (OPFRs) are emerging pollutants that pose increasing health risks. The association between urinary metabolites of OPFRs (m-OPFRs) and lipid metabolism remains unclear. This study evaluated lipid metabolism disorders of OPFRs in a population-based observational study and C57BL/6 mice. Urinary m-OPFRs, serum lipid molecules, and biochemical biomarkers in serum were measured. Linear regression and quantile-based g-computation analyses assessed associations between m-OPFRs and lipid markers. Benchmark dose and 95% lower confidence limit (BMDL) for m-OPFRs were determined by Bayesian BMD analysis, and the health risk of internal exposure was further assessed by hazard quotient (HQ). Mediation analysis assessed whether lipid molecules mediated OPFRs-induced hepatotoxicity. Association analyses identified three m-OPFRs, including bis(1-chloro-2-propyl) phosphate (BCIPP), diphenyl phosphate (DPP), and bis(1,3-dichloro-2-propyl) phosphate (BDCIPP), which were significantly associated with the levels of docosahexaenoic acid, 18:0 choline phosphate (LysoPC (18:0)), and 18:0 phosphoethanolamine. The BMDLs of BCIPP, DPP, and BDCIPP were 1.320, 0.100, and 0.030 μg/L, respectively. BDCIPP showed the highest HQ (4.50), followed by BCIPP (2.30) and DPP (0.66), indicating that the non-cancer risk of BDCIPP should be of concern. TDCIPP exposure induced hepatotoxicity in mice. LysoPC (18:0) increased at early exposure and mediated 7.88-30.02% of hepatotoxicity (P < 0.05). In conclusion, TDCIPP may induce hepatic lipid toxicity.