PMID- 26386178 OWN - NLM STAT- MEDLINE DCOM- 20161006 LR - 20161230 IS - 1872-9738 (Electronic) IS - 0892-0362 (Linking) VI - 52 IP - Pt B DP - 2015 Nov-Dec TI - Use of alternative assays to identify and prioritize organophosphorus flame retardants for potential developmental and neurotoxicity. PG - 181-93 LID - S0892-0362(15)30031-3 [pii] LID - 10.1016/j.ntt.2015.09.003 [doi] AB - 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 muM, 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. CI - Published by Elsevier Inc. FAU - Behl, Mamta AU - Behl M AD - Division of the National Toxicology Program, National Institute of Environmental Health Sciences, Research Triangle Park, NC, USA. Electronic address: behlmv@niehs.nih.gov. FAU - Hsieh, Jui-Hua AU - Hsieh JH AD - Kelly Government Solutions, RTP, NC, USA. FAU - Shafer, Timothy J AU - Shafer TJ AD - Integrated Systems Toxicology Division, Office of Research and Development, National Health and Environmental Effects Research Laboratory, U.S. Environmental Protection Agency, RTP, NC, USA. FAU - Mundy, William R AU - Mundy WR AD - Integrated Systems Toxicology Division, Office of Research and Development, National Health and Environmental Effects Research Laboratory, U.S. Environmental Protection Agency, RTP, NC, USA. FAU - Rice, Julie R AU - Rice JR AD - Division of the National Toxicology Program, National Institute of Environmental Health Sciences, Research Triangle Park, NC, USA. FAU - Boyd, Windy A AU - Boyd WA AD - Division of the National Toxicology Program, National Institute of Environmental Health Sciences, Research Triangle Park, NC, USA. FAU - Freedman, Jonathan H AU - Freedman JH AD - Department of Pharmacology and Toxicology, University of Louisville Health Sciences Center, Louisville, KY, USA. FAU - Hunter, E Sidney 3rd AU - Hunter ES 3rd AD - Integrated Systems Toxicology Division, Office of Research and Development, National Health and Environmental Effects Research Laboratory, U.S. Environmental Protection Agency, RTP, NC, USA. FAU - Jarema, Kimberly A AU - Jarema KA AD - Integrated Systems Toxicology Division, Office of Research and Development, National Health and Environmental Effects Research Laboratory, U.S. Environmental Protection Agency, RTP, NC, USA. FAU - Padilla, Stephanie AU - Padilla S AD - Integrated Systems Toxicology Division, Office of Research and Development, National Health and Environmental Effects Research Laboratory, U.S. Environmental Protection Agency, RTP, NC, USA. FAU - Tice, Raymond R AU - Tice RR AD - Division of the National Toxicology Program, National Institute of Environmental Health Sciences, Research Triangle Park, NC, USA. LA - eng PT - Journal Article DEP - 20150918 PL - United States TA - Neurotoxicol Teratol JT - Neurotoxicology and teratology JID - 8709538 RN - 0 (Flame Retardants) RN - 0 (Organophosphorus Compounds) SB - IM MH - Action Potentials/drug effects MH - Animals MH - Caenorhabditis elegans MH - Cell Survival/drug effects MH - Cells, Cultured MH - Cerebral Cortex/*drug effects/physiopathology MH - Embryonic Development/*drug effects MH - Embryonic Stem Cells/*drug effects MH - Flame Retardants/*toxicity MH - Humans MH - Mice MH - Neurites/drug effects MH - Neurons/*drug effects/physiology MH - Organophosphorus Compounds/*toxicity MH - Rats MH - Zebrafish OTO - NOTNLM OT - Caenorhabditis elegans OT - Flame retardants OT - developmental toxicity OT - embryonic stem cells OT - neurotoxicity OT - zebrafish EDAT- 2015/09/20 06:00 MHDA- 2016/10/08 06:00 CRDT- 2015/09/20 06:00 PHST- 2015/06/17 00:00 [received] PHST- 2015/09/02 00:00 [revised] PHST- 2015/09/02 00:00 [accepted] PHST- 2015/09/20 06:00 [entrez] PHST- 2015/09/20 06:00 [pubmed] PHST- 2016/10/08 06:00 [medline] AID - S0892-0362(15)30031-3 [pii] AID - 10.1016/j.ntt.2015.09.003 [doi] PST - ppublish SO - Neurotoxicol Teratol. 2015 Nov-Dec;52(Pt B):181-93. doi: 10.1016/j.ntt.2015.09.003. Epub 2015 Sep 18.