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Title: Multiparameter toxicity assessment of novel DOPO-derived organophosphorus flame retardants
Authors : Hirsch, Cordula
Striegl, Britta
Mathes, Stephanie
Adlhart, Christian
Edelmann, Michael
Bono, Epifania
Gaan, Sabyasachi
Salmeia, Khalifah A.
Hölting, Lise
Krebs, Alice
Nyffeler, Johanna
Pape, Regina
Bürkle, Alexander
Leist, Marcel
Wick, Peter
Schildknecht, Stefan
Published in : Archives of Toxicology
Volume(Issue) : 91
Issue : 1
Pages : 407
Pages to: 425
Publisher / Ed. Institution : Springer
Publisher / Ed. Institution: Berlin
Issue Date: 1-Mar-2017
License (according to publishing contract) : Licence according to publishing contract
Type of review: Peer review (Publication)
Language : English
Subjects : Flame retardants; Organophosphate; Dermal absorption; Neurotoxicity; Polybrominated diphenyls
Subject (DDC) : 615: Pharmacology and therapeutics
Abstract: 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 neuroselective cytotoxicity at concentrations ≥10 μM. 6-(2-((6-Oxidodibenzo[1,2]oxaphosphinin-6-yl)amino)ethoxydibenzo[1,2]oxaphosphinine-6-oxide) (ETA-DOPO) and 6,6′-(ethane-1,2-diylbis(oxy))bis(dibenzo[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[1,2]oxaphosphine-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.
Departement: Life Sciences und Facility Management
Organisational Unit: Institute of Chemistry and Biotechnology (ICBT)
Publication type: Article in scientific Journal
DOI : 10.1007/s00204-016-1680-4
ISSN: 0340-5761
Appears in Collections:Publikationen Life Sciences und Facility Management

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