Early Zebrafish Embryogenesis Is Susceptible to Developmental TDCPP Exposure

Sean P. McGee,¹ Ellen M. Cooper,² Heather M. Stapleton,² and David C. Volz¹

¹Department of Environmental Health Sciences, Arnold School of Public Health, University of South Carolina, Columbia, South Carolina, USA; ²Division of Environmental Sciences and Policy, Nicholas School of the Environment, Duke University, Durham, North Carolina, USA


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.


Objectives: 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.


Key words: cleavage, DNA methylation, embryogenesis, flame retardant, TDCPP, zebrafish. 


Environ Health Perspect 120:1585–1591 (2012). http://dx.doi.org/10.1289/ehp.1205316 [Online 6 September 2012]


Address correspondence to D. Volz, Department of Environmental Health Sciences, Arnold School of Public Health, University of South Carolina, 921 Assembly St., Columbia, SC 29208 USA. Telephone: (803) 777-0218. Fax: (803) 777-3391. E-mail: volz@mailbox.sc.edu


Supplemental Material is available online (http://dx.doi.org/10.1289/ehp.1205316).


We thank V.N. Belov (Max Planck Institute for Biophysical Chemistry, Goettingen, Germany) for synthesis of D₁₅-TDCPP, D₁₀-BDCPP, and D₁₀‑DPP; and R. Tanguay (Oregon State University, Corvallis, OR) for providing founder fish to establish our wild-type (5D) zebrafish colony. 


H.M.S. and E.M.C. were funded by a grant from the National Institute of Environmental Health Sciences (R01ESO16099).


The authors declare they have no actual or potential competing financial interests.


Received 6 April 2012; Accepted 6 September 2012; Online 6 September 2012.