1 Organophosphorus Flame Retardants Inhibit Specific Liver 2 Carboxylesterases and Cause Serum Hypertriglyceridemia

9 ABSTRACT: Humans are prevalently exposed to organo-10 phosphorus flame retardants (OPFRs) contained in consumer 11 products and electronics, though their toxicological effects and 12 mechanisms remain poorly understood. We show here that 13 OPFRs inhibit specific liver carboxylesterases (Ces) and causes 14 altered hepatic lipid metabolism. Ablation of the OPFR targets 15 Ces1g has been previously linked to dyslipidemia in mice. 16 Consistent with OPFR inhibition of Ces1g, we also observe 17 OPFR-induced serum hypertriglyceridemia in mice. Our findings 18 suggest novel toxicities that may arise from OPFR exposure and 19 highlight the utility of chemoproteomic and metabolomic 20 platforms in the toxicological characterization of environmental 21 chemicals. 22 Flame retardant chemicals are added to furniture, textiles, 23 vehicle upholstery, electronics, computers, plastics, buildin