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Use of alternative assays to identify and prioritize organophosphorus flame retardants for potential developmental and neurotoxicity.

Publication ,  Journal Article
Behl, M; Hsieh, J-H; Shafer, TJ; Mundy, WR; Rice, JR; Boyd, WA; Freedman, JH; Hunter, ES; Jarema, KA; Padilla, S; Tice, RR
Published in: Neurotoxicology and teratology
November 2015

Due to their toxicity and persistence in the environment, brominated flame retardants (BFRs) are being phased out of commercial use, leading to the increased use of alternative chemicals such as the organophosphorus flame retardants (OPFRs). There is, however, limited information on the potential health effects of OPFRs. Due to the structural similarity of the OPFRs to organophosphorus insecticides, there is concern regarding developmental toxicity and neurotoxicity. In response, we evaluated a set of OPFRs (triphenyl phosphate [TPHP]), isopropylated phenyl phosphate [IPP], 2-ethylhexyl diphenyl phosphate [EHDP], tert-butylated phenyl diphenyl phosphate [BPDP], trimethyl phenyl phosphate [TMPP], isodecyl diphenyl phosphate [IDDP], (tris(1,3-dichloroisopropyl) phosphate [TDCIPP], and tris(2-chloroethyl)phosphate [TCEP]) in a battery of cell-based in vitro assays and alternative model organisms and compared the results to those obtained for two classical BFRs (3,3',5,5'-tetrabromobisphenol A [TBBPA] and 2,2'4,4'-brominated diphenyl ether [BDE-47]). The assays used evaluated the effects of chemicals on the differentiation of mouse embryonic stem cells, the proliferation and growth of human neural stem cells, rat neuronal growth and network activity, and development of nematode (Caenorhabditis elegans) and zebrafish (Danio rerio). All assays were performed in a concentration-response format, allowing for the determination of the point of departure (POD: the lowest concentration where a chemically-induced response exceeds background noise). The majority of OPFRs (8/9) were active in multiple assays in the range of 1-10 μM, most of which had comparable activity to the BFRs TBBPA and BDE-47. TCEP was negative in all assays. The results indicate that the replacement OPFRs, with the exception of TCEP, showed comparable activity to the two BFRs in the assays tested. Based on these results, more comprehensive studies are warranted to further characterize the potential hazard of some of these OPFR compounds.

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Published In

Neurotoxicology and teratology

DOI

EISSN

1872-9738

ISSN

0892-0362

Publication Date

November 2015

Volume

52

Issue

Pt B

Start / End Page

181 / 193

Related Subject Headings

  • Zebrafish
  • Toxicology
  • Rats
  • Organophosphorus Compounds
  • Neurons
  • Neurites
  • Mice
  • Humans
  • Flame Retardants
  • Embryonic Stem Cells
 

Citation

APA
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ICMJE
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Behl, M., Hsieh, J.-H., Shafer, T. J., Mundy, W. R., Rice, J. R., Boyd, W. A., … Tice, R. R. (2015). Use of alternative assays to identify and prioritize organophosphorus flame retardants for potential developmental and neurotoxicity. Neurotoxicology and Teratology, 52(Pt B), 181–193. https://doi.org/10.1016/j.ntt.2015.09.003
Behl, Mamta, Jui-Hua Hsieh, Timothy J. Shafer, William R. Mundy, Julie R. Rice, Windy A. Boyd, Jonathan H. Freedman, et al. “Use of alternative assays to identify and prioritize organophosphorus flame retardants for potential developmental and neurotoxicity.Neurotoxicology and Teratology 52, no. Pt B (November 2015): 181–93. https://doi.org/10.1016/j.ntt.2015.09.003.
Behl M, Hsieh J-H, Shafer TJ, Mundy WR, Rice JR, Boyd WA, et al. Use of alternative assays to identify and prioritize organophosphorus flame retardants for potential developmental and neurotoxicity. Neurotoxicology and teratology. 2015 Nov;52(Pt B):181–93.
Behl, Mamta, et al. “Use of alternative assays to identify and prioritize organophosphorus flame retardants for potential developmental and neurotoxicity.Neurotoxicology and Teratology, vol. 52, no. Pt B, Nov. 2015, pp. 181–93. Epmc, doi:10.1016/j.ntt.2015.09.003.
Behl M, Hsieh J-H, Shafer TJ, Mundy WR, Rice JR, Boyd WA, Freedman JH, Hunter ES, Jarema KA, Padilla S, Tice RR. Use of alternative assays to identify and prioritize organophosphorus flame retardants for potential developmental and neurotoxicity. Neurotoxicology and teratology. 2015 Nov;52(Pt B):181–193.
Journal cover image

Published In

Neurotoxicology and teratology

DOI

EISSN

1872-9738

ISSN

0892-0362

Publication Date

November 2015

Volume

52

Issue

Pt B

Start / End Page

181 / 193

Related Subject Headings

  • Zebrafish
  • Toxicology
  • Rats
  • Organophosphorus Compounds
  • Neurons
  • Neurites
  • Mice
  • Humans
  • Flame Retardants
  • Embryonic Stem Cells