Multiparameter toxicity assessment of novel DOPO-derived organophosphorus flame retardants

Autor: Britta Striegl, Marcel Leist, Alexander Bürkle, Michael Edelmann, Christian Adlhart, Cordula Hirsch, Stefan Schildknecht, Khalifah A. Salmeia, Stephanie Mathes, Lisa Hoelting, Johanna Nyffeler, Peter Wick, Alice Krebs, Regina Pape, Sabyasachi Gaan, Epifania Bono
Rok vydání: 2016
Předmět:
Keratinocytes
Health
Toxicology and Mutagenesis
Human Embryonic Stem Cells
Sus scrofa
Dermal absorption
02 engineering and technology
010501 environmental sciences
Toxicology
01 natural sciences
Monocytes
615: Pharmakologie und Therapeutik
chemistry.chemical_compound
Polybrominated diphenyl ethers
Organophosphate
Organic chemistry
Cytotoxicity
Cells
Cultured
Skin
Polyurethane
Neurons
Tissue Scaffolds
General Medicine
021001 nanoscience & nanotechnology
In vitro Systems
Toxicity
Alkoxy group
0210 nano-technology
Pluripotent Stem Cells
Cell Survival
Skin Absorption
Respiratory Mucosa
Flame retardants
Cell Line
Organophosphorus Compounds
ddc:570
Toxicity Tests
Neurotoxicity
medicine
Animals
Humans
Polybrominated diphenyls
0105 earth and related environmental sciences
Skin Irritancy Tests
medicine.disease
Cyclic P-Oxides
chemistry
A549 Cells
Neural crest cell migration
Zdroj: Archives of Toxicology
ISSN: 1432-0738
0340-5761
Popis: 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. Electronic supplementary material The online version of this article (doi:10.1007/s00204-016-1680-4) contains supplementary material, which is available to authorized users.
Databáze: OpenAIRE
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