Multiparameter toxicity assessment of novel DOPO-derived organophosphorus flame retardants
Authors
Cordula Hirsch , Britta Striegl , Stephanie Mathes , Christian Adlhart, Michael Edelmann , Epifania Bono , Sabyasachi Gaan , Khalifah A. Salmeia , Lisa Hoelting
Institution
ZHAW
Country
Switzerland
Year
2016
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 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(6Hdibenzo[
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.