Early Zebrafish Embryogenesis Is Susceptible to Developmental TDCPP Exposure
Publication: Environmental Health Perspectives
Volume 120, Issue 11
Pages 1585 - 1591
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.
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References
Babich M. 2006. CPSC Staff Preliminary Risk Assessment of Flame Retardant (FR) Chemicals in Upholstered Furniture Foam. Available: http://www.cpsc.gov/library/foia/foia07/brief/ufurn2.pdf [accessed 6 April 2012].
Bloom S. 1984. Sister chromatid exchange studies in the chick embryo and neonate: actions of mutagens in a developing system. Basic Life Sci 29(pt B):509-533 https://www.ncbi.nlm.nih.gov/pubmed/6397191.
Brusick D, Matheson D, Jagannath D, Goode S, Lebowitz H, Reed M. 1980. A comparison of the genotoxic properties of tris(2,3-dibromopropyl)phosphate and tris(1,3-dichloro-2-propyl)phosphate in a battery of short-term bioassays. J Environ Pathol Toxicol 3(1–2):207 https://www.ncbi.nlm.nih.gov/pubmed/7441080.
Cifone M. 2005. In Vivo/in Vitro Unscheduled DNA Synthesis in Rat Primary Hepatocyte Cultures at Two Timepoints with a Dose Range Finding Assay. Vienna, VA Covance Laboratories.
Cooper EM, Covaci A, van Nuijs AL, Webster TF, Stapleton HM. 2011. Analysis of the flame retardant metabolites bis(1,3-dichloro-2-propyl) phosphate (BDCPP) and diphenyl phosphate (DPP) in urine using liquid chromatography–tandem mass spectrometry. Anal Bioanal Chem 401(7):2123-2132 https://www.ncbi.nlm.nih.gov/pubmed/21830137.
Duffy KT, McAleer MF, Davidson WR, Kari L, Kari C, Liu CGet al. 2005. Coordinate control of cell cycle regulatory genes in zebrafish development tested by cyclin D1 knockdown with morpholino phosphorodiamidates and hydroxyprolyl-phosphono peptide nucleic acids. Nucleic Acids Res 33(15):4914-4921 https://www.ncbi.nlm.nih.gov/pubmed/16284195.
Ikegami R, Hunter P, Yager TD. 1997. Developmental activation of the capability to undergo checkpoint-induced apoptosis in the early zebrafish embryo. Dev Biol 209(2):409-433 https://www.ncbi.nlm.nih.gov/pubmed/10328930.
Kimmel CB, Ballard WW, Kimmel SR, Ullmann B, Schilling TF. 1995. Stages of embryonic development of the zebrafish. Dev Dyn 203(3):253-310 https://www.ncbi.nlm.nih.gov/pubmed/8589427.
LeBel GL, Williams DT. 1983. Determination of organic phosphate triesters in human adipose tissue. J Assoc Off Anal Chem 66(3):691-699 https://www.ncbi.nlm.nih.gov/pubmed/6863190.
LeBel GL, Williams DT, Berard D. 1989. Triaryl/alkyl phosphate residues in human adipose autopsy samples from six Ontario municipalities. Bull Environ Contam Toxicol 43(2):225-230 https://www.ncbi.nlm.nih.gov/pubmed/2775890.
Marklund A, Anderson B, Haglund P. 2003. Screening of organophosphorus compounds and their distribution in various indoor environments. Chemosphere 53(9):1137-1146 https://www.ncbi.nlm.nih.gov/pubmed/14512118.
Martin CC, Laforest L, Akimenko MA, Ekker M. 1999. A role for DNA methylation in gastrulation and somite patterning. Dev Biol 206(2):189-205 https://www.ncbi.nlm.nih.gov/pubmed/9986732.
Meeker JD, Stapleton HM. 2010. House dust concentrations of organophosphate flame retardants in relation to hormone levels and semen quality parameters. Environ Health Perspect 118:318-323 https://www.ncbi.nlm.nih.gov/pubmed/20194068.
Mhanni AA, McGowan RA. 2004. Global changes in genomic methylation levels during early development of the zebrafish embryo. Dev Genes Evol 214(8):412-417 https://www.ncbi.nlm.nih.gov/pubmed/15309635.
Morales N, Matthews HB. 1980. In vivo binding of the flame retardants tris-2,3-dibromopropyl phosphate and tris-1,3-dichloro-2-propyl phosphate to macromolecules of mouse liver, kidney and muscle. Bull Environ Contam Toxicol 25(1):34-38 https://www.ncbi.nlm.nih.gov/pubmed/6161654.
Nomeir AA, Kato S, Matthews HB. 1981. The metabolism and disposition of tris(1,3-dichloro-2-propyl) phosphate (Fyrol FR-2) in the rat. Toxicol Appl Pharmacol 57(3):401-413 https://www.ncbi.nlm.nih.gov/pubmed/7222047.
Padilla S, Corum D, Padnos B, Hunter DL, Beam A, Houck KAet al. 2012. Zebrafish developmental screening of the ToxCast Phase I chemical library. Reprod Toxicol 33(2):174-187 https://www.ncbi.nlm.nih.gov/pubmed/22182468.
Rahman F, Langford KH, Scrimshaw MD, Lester JN. 2001. Polybrominated diphenyl ether (PBDE) flame retardants. Sci Total Environ 275(1–3):1-17 https://www.ncbi.nlm.nih.gov/pubmed/11482396.
Stapleton HM, Klosterhaus S, Eagle S, Fuh J, Meeker JD, Blum Aet al. 2009. Detection of organophosphate flame retardants in furniture foam and U.S. house dust. Environ Sci Technol 43(19):7490-7495 https://www.ncbi.nlm.nih.gov/pubmed/19848166.
Stapleton HM, Klosterhaus S, Keller A, Ferguson PL, van Bergen S, Cooper Eet al. 2011. Identification of flame retardants in polyurethane foam collected from baby products. Environ Sci Technol 45(12):5323-5331 https://www.ncbi.nlm.nih.gov/pubmed/21591615.
State of California. 2000. Requirements, Test Procedure and Apparatus for Testing the Flame Retardance of Resilient Filling Materials Used in Upholstered Furniture. Technical Bulletin 117. North Highlands, CA:Bureau of Home Furnishings and Thermal Insulation. Available: http://www.bhfti.ca.gov/industry/117.pdf [accessed 6 April 2012].
Tadros W, Lipshitz HD. 2009. The maternal-to-zygotic transition: a play in two acts. Development 136(18):3033-3042 https://www.ncbi.nlm.nih.gov/pubmed/19700615.
Tullo A. 2003. Great Lakes to phase out two flame-retardants. Chem Eng News 81(45):13.
U.S. EPA (U.S. Environmental Protection Agency). 2005. Environmental Profiles of Chemical Flame-Retardant Alternatives for Low-Density Polyurethane Foam. Washington, DC:U.S. EPA. Available: http://www.epa.gov/dfe/pubs/flameret/ffr-alt.htm [accessed 6 April 2012].
Information & Authors
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Published In
Environmental Health Perspectives
Volume 120 • Issue 11 • November 2012
Pages: 1585 - 1591
PubMed: 23017583
License Information
EHP is an open-access journal published with support from the National Institute of Environmental Health Sciences, National Institutes of Health. All content is public domain unless otherwise noted.
History
Received: 6 April 2012
Accepted: 6 September 2012
Published online: 6 September 2012
Keywords
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Competing Interests
The authors declare they have no actual or potential competing financial interests.
Funding Information
H.M.S. and E.M.C. were funded by a grant from the National Institute of Environmental Health Sciences (R01ESO16099).
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