Effects Of Tris ?1,3-Dichloro-2-Propyl? Phosphate On Growth And Reproduction In Zebrafish Exposed To Environmentally Relevant Concentrations

Tris(1,3-dichloro-2-propyl)phosphate(TDCIPP)is a synthetic organophosphate flame retardant and plasticizer that has been used for decades in various products,such as plastics,foams,textiles,varnishes,electronics equipment,and furniture.Recently,because the use of brominated flame retardants is generally being voluntarily reduced and phased out or banned,the consumption of organophosphate flame retardants such as TDCIPP has been increasing.TDCIPP is an additive flame retardant that is not chemically bonded to polymeric products,whereas reactive flame retardants are chemically bonded into products.Therefore,TDCIPP is more likely to be released into the environment,as evidenced by its frequent detection in aquatic environmental compartments.Currently TDCIPP can be detected in drinking water,rivers and sewage with concentrations ranging from tens to thousands of ng/L all around the world.However,current toxicological test on TDCIPP mainly focuses on acute exposure with high concentrations,which are much higher than it exists in the environment.In order to study the potential risk of TDCIPP to environment and human health,zebrafish were used as the living body model for toxicological experiments.In this study,the effects of environmentally relevant concentrations of TDCIPP(50,500 and 5000 ng/L)exposure on growth and reproduction in zebrafish were evaluated through studying the change of the hypothalamic-pituitary-thyroid(HPT)axis,growth hormone/insulin-like growth factor(GH/IGF)axis and hypothalamic-pituitary-gonadal(HPG)axis.The main findings are as follows:1.Exposure to environmentally relevant concentrations of TDCIPP resulted in female-biased growth inhibition and lesser production of eggs than in unexposed controls,but it did not affect histology of the gonads,plasma concentrations of steroid hormone,or expression of genes involved in the HPG axis.These results demonstrated that the toxicity of TDCIPP was not caused by disruption of the HPG axis.In this study,for the first time,we found that TDCIPP caused a female-biased down-regulation of GH/IGF genes,which may be responsible for the observed female-biased inhibitory effects on growth and lesser production of eggs.This study suggested that inhibition of growth might be a primary apical response of zebrafish.2.For the first time,zebrafish growth curves were used for toxicological exposure experiments.In this study,zebrafish growth curves were produced to determine the sampling time points,and then to study the time-dependent effect of developmental toxicity of TDCIPP.Exposure to environmentally relevant concentrations of TDCIPP inhibited growth of female zebrafish and changed the expression of genes along the GH/IGF axis in a time-dependent manner.However,TDCIPP exprosure did not affect plasma concentrations of thyroid hormones or expression of genes along the HPT axis,which indicated that the GH/IGF signaling pathway might be a key target for effects of TDCIPP.