Behl Mamta, Rice Julie R, Smith Marjo V, Co Caroll A, Bridge Matthew F, Hsieh Jui-Hua, Freedman Jonathan H, Boyd Windy A
Division of the National Toxicology Program, National Institute of Environmental Health Sciences, NIH, Research Triangle Park, North Carolina.
Social & Scientific Systems, Inc., Durham, North Carolina.
Toxicol Sci. 2016 Dec;154(2):241-252. doi: 10.1093/toxsci/kfw162. Epub 2016 Aug 26.
With the phasing-out of the polybrominated diphenyl ether (PBDE) flame retardants due to concerns regarding their potential developmental toxicity, the use of replacement compounds such as organophosphate flame retardants (OPFRs) has increased. Limited toxicity data are currently available to estimate the potential adverse health effects of the OPFRs. The toxicological effects of 4 brominated flame retardants, including 3 PBDEs and 3,3',5,5'-tetrabromobisphenol A, were compared with 6 aromatic OPFRs and 2 aliphatic OPFRs. The effects of these chemicals were determined using 3 biological endpoints in the nematode Caenorhabditis elegans (feeding, larval development, and reproduction). Because C. elegans development was previously reported to be sensitive to mitochondrial function, results were compared with those from an in vitro mitochondrial membrane permeabilization (MMP) assay. Overall 11 of the 12 flame retardants were active in 1 or more C. elegans biological endpoints, with only tris(2-chloroethyl) phosphate inactive across all endpoints including the in vitro MMP assay. For 2 of the C. elegans endpoints, at least 1 OPFR had similar toxicity to the PBDEs: triphenyl phosphate (TPHP) inhibited larval development at levels comparable to the 3 PBDEs; whereas TPHP and isopropylated phenol phosphate (IPP) affected C. elegans reproduction at levels similar to the PBDE commercial mixture, DE-71. The PBDEs reduced C. elegans feeding at lower concentrations than any OPFR. In addition, 9 of the 11 chemicals that inhibited C. elegans larval development also caused significant mitochondrial toxicity. These results suggest that some of the replacement aromatic OPFRs may have levels of toxicity comparable to PBDEs.
由于对多溴二苯醚（PBDE）阻燃剂潜在的发育毒性存在担忧，这类阻燃剂正逐步被淘汰，有机磷酸酯阻燃剂（OPFR）等替代化合物的使用有所增加。目前关于OPFR潜在健康不良影响的毒性数据有限。将4种溴化阻燃剂（包括3种PBDE和3,3',5,5'-四溴双酚A）的毒理学效应与6种芳香族OPFR和2种脂肪族OPFR进行了比较。使用秀丽隐杆线虫的3个生物学终点（摄食、幼虫发育和繁殖）来确定这些化学物质的效应。由于之前报道秀丽隐杆线虫的发育对线粒体功能敏感，因此将结果与体外线粒体膜通透性（MMP）试验的结果进行了比较。总体而言，12种阻燃剂中的11种在秀丽隐杆线虫的1个或多个生物学终点上具有活性，只有磷酸三（2-氯乙基）酯在包括体外MMP试验在内的所有终点上均无活性。对于秀丽隐杆线虫的2个终点，至少有一种OPFR与PBDE具有相似的毒性：磷酸三苯酯（TPHP）抑制幼虫发育的水平与3种PBDE相当；而TPHP和异丙基化磷酸苯酚酯（IPP）影响秀丽隐杆线虫繁殖的水平与PBDE商业混合物DE-71相似。PBDE在比任何OPFR更低的浓度下就能降低秀丽隐杆线虫的摄食。此外，11种抑制秀丽隐杆线虫幼虫发育的化学物质中有9种也会导致显著的线粒体毒性。这些结果表明，一些替代的芳香族OPFR的毒性水平可能与PBDE相当。
