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
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: firstname.lastname@example.org
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.
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