摘要：Ba c k g r o u n d: Chlorinated phosphate esters (CPEs) are widely used as additive flame retardants for low-density polyurethane foams and have frequently been detected at elevated concentrations within indoor environmental media.oB j e c t i v e s: To begin characterizing the potential toxicity of CPEs on early vertebrate development, we examined the develop mental toxicity of four CPEs used in polyurethane foam: tris(1,3-dichloro-2-propyl) phosphate (TDCPP), tris(2-chloroethyl) phosphate (TCEP), tris(1-chloro-2-propyl) phosphate (TCPP), and 2,2-bis(chloromethyl)propane-1,3-diyl tetrakis(2-chlorethyl) bis(phosphate) (V6).Me t h o d s: Using zebrafish as a model for vertebrate embryogenesis, we first screened the potential terato genic effects of TDCPP, TCEP, TCPP, and V6 using a develop mental toxicity assay. Based on these results, we focused on identification of susceptible windows of develop mental TDCPP exposure as well as evaluation of uptake and elimination of TDCPP and bis(1,3-dichloro-2-propyl)phosphate (BDCPP, the primary metabolite) within whole embryos. Finally, because TDCPP-specific genotoxicity assays have, for the most part, been negative in vivo and because zygotic genome remethyla tion is a key biological event during cleavage, we investigated whether TDCPP altered the status of zygotic genome methylation during early zebrafish embryogenesis.re s u l t s: Overall, our findings suggest that the cleavage period during zebrafish embryogenesis is susceptible to TDCPP-induced delays in remethylation of the zygotic genome, a mechanism that may be associated with enhanced develop mental toxicity following initiation of TDCPP exposure at the start of cleavage.co n c l u s i o n s: Our results suggest that further research is needed to better understand the effects of a widely used and detected CPE within susceptible windows of early vertebrate develop ment
关键词：cleavage; DNA methylation; embryogenesis; flame retardant; TDCPP; zebrafish
