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Multiparameter toxicity assessment of novel DOPO-derived organophosphorus flame retardants

Multiparameter toxicity assessment of novel DOPO-derived organophosphorus flame retardants

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HIRSCH, Cordula, Britta STRIEGL, Stephanie MATHES, Christian ADLHART, Alice KREBS, Johanna NYFFELER, Regina PAPE, Alexander BÜRKLE, Marcel LEIST, Stefan SCHILDKNECHT, 2017. Multiparameter toxicity assessment of novel DOPO-derived organophosphorus flame retardants. In: Archives of Toxicology. 91(1), pp. 407-425. ISSN 0003-9446. eISSN 1432-0738. Available under: doi: 10.1007/s00204-016-1680-4

@article{Hirsch2017-01Multi-33769, title={Multiparameter toxicity assessment of novel DOPO-derived organophosphorus flame retardants}, year={2017}, doi={10.1007/s00204-016-1680-4}, number={1}, volume={91}, issn={0003-9446}, journal={Archives of Toxicology}, pages={407--425}, author={Hirsch, Cordula and Striegl, Britta and Mathes, Stephanie and Adlhart, Christian and Krebs, Alice and Nyffeler, Johanna and Pape, Regina and Bürkle, Alexander and Leist, Marcel and Schildknecht, Stefan} }

Mathes, Stephanie Adlhart, Christian Pape, Regina Adlhart, Christian Multiparameter toxicity assessment of novel DOPO-derived organophosphorus flame retardants Krebs, Alice Bürkle, Alexander Striegl, Britta Bürkle, Alexander Nyffeler, Johanna Nyffeler, Johanna eng Hirsch, Cordula 2016-05-02T13:34:12Z Schildknecht, Stefan Attribution 4.0 International Leist, Marcel Schildknecht, Stefan Hirsch, Cordula Leist, Marcel 2016-05-02T13:34:12Z Mathes, Stephanie Striegl, Britta Krebs, Alice 2017-01 Pape, Regina Halogen-free organophosphorus flame retardants are considered as replacements for the phased-out class of polybrominated diphenyl ethers (PBDEs). However, toxicological information on new flame retardants is still limited. Based on their excellent flame retardation potential, we have selected three novel 9,10-dihydro-9-oxa-10-phosphaphenanthrene-10-oxide (DOPO) derivatives and assessed their toxicological profile using a battery of in vitro test systems in order to provide toxicological information before their large-scale production and use. PBDE-99, applied as a reference compound, exhibited distinct neuro-selective cytotoxicity at concentrations ≥10 µM. 6-(2-((6-oxido-6H-dibenzo[c,e][1,2]oxaphosphinin-6-yl)amino)ethoxy)-6H-dibenzo[c,e][1,2]oxaphosphinine 6-oxide (ETA-DOPO) and 6,6'-(ethane-1,2-diylbis(oxy))bis(6H-dibenzo[c,e][1,2]oxaphosphinine-6-oxide) (EG-DOPO) displayed adverse effects at concentrations >10 µM in test systems reflecting the properties of human central and peripheral nervous system neurons, as well as in a set of non-neuronal cell types. DOPO and its derivative 6,6'-(ethane-1,2-diylbis(azanediyl))bis(6H-dibenzo[c,e][1,2]oxaphosphinine-6-oxide) (EDA-DOPO) were neither neurotoxic, nor did they exhibit an influence on neural crest cell migration, or on the integrity of human skin equivalents. The two compounds furthermore displayed no inflammatory activation potential, nor did they affect algae growth or daphnia viability at concentrations ≤400 µM. Based on the superior flame retardation properties, biophysical features suited for use in polyurethane foams, and low cytotoxicity of EDA-DOPO, our results suggest that it is a candidate for the replacement of currently applied flame retardants.

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