Parental Transfer Of Tris(1,3-dichloro-2-propyl) Phosphate(TDCIPP) And Development Toxicity Of Zebrafish Exposed To Environmentally Relevant Concentrations

As a class of replacements for the commercial PentaBDE mixture,Tris(1,3-dichloro-2-propyl)phosphate(TDCIPP)has been frequently detected in foam used in furniture and baby products,and thus humans are the most likely to be chronic exposed.However,limited information is currently available about the toxic effects and mechanisms of TDCIPP,the developmental toxicity as well as the possible prenatal transfer of TDCIPP at environmentally relevant concentration are still unclear.In the present study,using zebrafish as a model,we investigated the effects on the growth and development in initial generation(F0)zebrafish after chronic exposure to environmentally relevant concentrations of TDCIPP for 240 days,and examined the possible parental transfer of TDCIPP as well as transgenerational effects of firstgeneration(F1)larvae.1.When zebrafish(1 month old)were exposed to 580 ng/L or 7500 ng/L TDCIPP for 240 days,bioconcentration resulted in significantly less growth as measured from body length,body mass,brain-somatic index(BSI)and hepatic-somatic index(HSI)in F0 females but not F0 males.These effects were possibly due to down-regulation of expression of genes along the growth hormone/insulin-like growth factor(GH/IGF)axis.Furthermore,residues of TDCIPP were detected in F1 eggs after parental exposure,which resulted in reduced survival,body length and heart rate in F1 individuals.Down-regulation of genes in the GH/IGF axis(e.g,gh,igf1)might be responsible for transgenerational toxicity.This study provides the first known evidence that exposure of zebrafish to environmentally relevant concentrations of TDCIPP during development can inhibit growth of offspring,which were not exposed directly to TDCIPP.2.After zebrafish(1 month old)were exposed to TDCIPP(580 ng/L or 7500 ng/L)for 240 days,the results demonstrated that environmentally relevant concentrations of TDCIPP could increase the plasma levels of total 3,5,3'-trooodothyronine(T3);as well as alter the mRNA levels of systhesis genes(thyrotropin?-subunit(tsh?),metabolic gene(Deiodinases(dio2))and cytosolic sulfotransferase(sult1 st5)and TH receptor(tr?)in the females after a long-term TDCIPP exposure.The effects of TDCIPP in disturbing thyroid function may be another reason for inhibiting growth in female zebrafish.3.Meanwhile,we investigated the transgenerational neurotoxicity of the environmentally relevant concentrations of TDCIPP.The results declared that TDCIPP significantly decreased the locomotion activity of F1 5-dpf larvae and the mRNA expression of genes associated with neuronal development(e.g,gap43,?1-tubulin).The study firstly provides evidence that TDCIPP exposure at environmentally relevant concentrations can induce transgenerational neurotoxicity in un-exposed F1 zebrafish larvae.Collectively,the data suggested that effects on growth and development with transgenerational toxicity of environmental concentrations of TDCIPP could currently be having significant adverse effects at some locations in the environment,and these data might be useful for risk prediction of TDCIPP.