title: Early zebrafish embryogenesis is susceptible to developmental TDCPP exposure.
abstract: BACKGROUND
  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.
  
  
  OBJECTIVE
  To begin characterizing the potential toxicity of CPEs on early vertebrate development, we examined the developmental 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).
  
  
  METHODS
  Using zebrafish as a model for vertebrate embryogenesis, we first screened the potential teratogenic effects of TDCPP, TCEP, TCPP, and V6 using a developmental toxicity assay. Based on these results, we focused on identification of susceptible windows of developmental 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 remethylation is a key biological event during cleavage, we investigated whether TDCPP altered the status of zygotic genome methylation during early zebrafish embryogenesis.
  
  
  RESULTS
  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 developmental toxicity following initiation of TDCPP exposure at the start of cleavage.
  
  
  CONCLUSIONS
  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 development.
authors.affiliation: Department of Environmental Health Sciences, Arnold School of Public Health, University of South Carolina, Columbia, South Carolina 29208, USA.
authors.forename: Sean P
authors.initials: SP
authors.lastname: McGee
authors.forename: Ellen M
authors.initials: EM
authors.lastname: Cooper
authors.forename: Heather M
authors.initials: HM
authors.lastname: Stapleton
authors.forename: David C
authors.initials: DC
authors.lastname: Volz
mesh_terms: D000818:Animals; D002853:Chromatography, Liquid; D019175:DNA Methylation / Q000187:drug effects*; D005411:Flame Retardants / Q000378:metabolism / Q000633:toxicity*; D018507:Gene Expression Regulation, Developmental / Q000187:drug effects*; D006843:Hydrocarbons, Chlorinated / Q000378:metabolism / Q000633:toxicity; D007928:Lethal Dose 50; D010755:Organophosphates / Q000378:metabolism* / Q000633:toxicity; D009943:Organophosphorus Compounds / Q000378:metabolism / Q000633:toxicity*; D015183:Restriction Mapping; D053719:Tandem Mass Spectrometry; D014874:Water Pollutants, Chemical / Q000633:toxicity*; D015027:Zebrafish / Q000196:embryology* / Q000235:genetics / Q000378:metabolism; D015053:Zygote / Q000187:drug effects / Q000254:growth & development / Q000378:metabolism
chemical_list: D005411:Flame Retardants; D006843:Hydrocarbons, Chlorinated; D010755:Organophosphates; D009943:Organophosphorus Compounds; D014874:Water Pollutants, Chemical; C016805:tris(1,3-dichloro-2-propyl)phosphate