Multiparameter toxicity assessment of novel DOPO-derived organophosphorus flame retardants.
| Title: | Multiparameter toxicity assessment of novel DOPO-derived organophosphorus flame retardants. |
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| Authors: | Hirsch C; Particles-Biology Interactions Laboratory, Swiss Federal Laboratories for Materials Science and Technology (Empa), Lerchenfeldstrasse 5, 9014, St. Gallen, Switzerland. Cordula.Hirsch@empa.ch.; Striegl B; ZHAW, Life Sciences and Facility Management, Einsiedlerstr. 31, 8820, Waedenswil, Switzerland.; Mathes S; ZHAW, Life Sciences and Facility Management, Einsiedlerstr. 31, 8820, Waedenswil, Switzerland.; Adlhart C; ZHAW, Life Sciences and Facility Management, Einsiedlerstr. 31, 8820, Waedenswil, Switzerland.; Edelmann M; ZHAW, Life Sciences and Facility Management, Einsiedlerstr. 31, 8820, Waedenswil, Switzerland.; Bono E; ZHAW, Life Sciences and Facility Management, Einsiedlerstr. 31, 8820, Waedenswil, Switzerland.; Gaan S; Additives and Chemistry Group, Advanced Fibers, Swiss Federal Laboratories for Materials Science and Technology (Empa), Lerchenfeldstrasse 5, 9014, St. Gallen, Switzerland.; Salmeia KA; Additives and Chemistry Group, Advanced Fibers, Swiss Federal Laboratories for Materials Science and Technology (Empa), Lerchenfeldstrasse 5, 9014, St. Gallen, Switzerland.; Hoelting L; University of Konstanz, Universitaetsstr. 10, 78457, Konstanz, Germany.; Krebs A; University of Konstanz, Universitaetsstr. 10, 78457, Konstanz, Germany.; Nyffeler J; University of Konstanz, Universitaetsstr. 10, 78457, Konstanz, Germany.; Pape R; University of Konstanz, Universitaetsstr. 10, 78457, Konstanz, Germany.; Bürkle A; University of Konstanz, Universitaetsstr. 10, 78457, Konstanz, Germany.; Leist M; University of Konstanz, Universitaetsstr. 10, 78457, Konstanz, Germany.; Wick P; Particles-Biology Interactions Laboratory, Swiss Federal Laboratories for Materials Science and Technology (Empa), Lerchenfeldstrasse 5, 9014, St. Gallen, Switzerland.; Schildknecht S; University of Konstanz, Universitaetsstr. 10, 78457, Konstanz, Germany. |
| Source: | Archives of toxicology [Arch Toxicol] 2017 Jan; Vol. 91 (1), pp. 407-425. Date of Electronic Publication: 2016 Feb 29. |
| Publication Type: | Journal Article |
| Language: | English |
| Journal Info: | Publisher: Springer-Verlag Country of Publication: Germany NLM ID: 0417615 Publication Model: Print-Electronic Cited Medium: Internet ISSN: 1432-0738 (Electronic) Linking ISSN: 03405761 NLM ISO Abbreviation: Arch Toxicol Subsets: MEDLINE |
| Imprint Name(s): | Original Publication: Berlin, New York, Springer-Verlag. |
| MeSH Terms: | Flame Retardants/*toxicity ; Keratinocytes/*drug effects ; Monocytes/*drug effects ; Neurons/*drug effects ; Organophosphorus Compounds/*toxicity ; Respiratory Mucosa/*drug effects ; Skin/*drug effects; Cell Survival/drug effects ; Cyclic P-Oxides/toxicity ; Human Embryonic Stem Cells/cytology ; Keratinocytes/cytology ; Keratinocytes/immunology ; Keratinocytes/metabolism ; Monocytes/cytology ; Monocytes/immunology ; Monocytes/metabolism ; Neurons/cytology ; Neurons/immunology ; Neurons/metabolism ; Pluripotent Stem Cells/cytology ; Respiratory Mucosa/cytology ; Respiratory Mucosa/immunology ; Respiratory Mucosa/metabolism ; Skin/cytology ; Skin/immunology ; Skin/metabolism ; Tissue Scaffolds/chemistry ; A549 Cells ; Animals ; Cell Line ; Cells, Cultured ; Humans ; Skin Absorption ; Skin Irritancy Tests ; Sus scrofa ; Toxicity Tests |
| 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(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. |
| Competing Interests: | The authors declare that they have no conflict of interest. |
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| Contributed Indexing: | Keywords: Dermal absorption; Flame retardants; Neurotoxicity; Organophosphate; Polybrominated diphenyls |
| Substance Nomenclature: | 0 (Cyclic P-Oxides); 0 (EDA-DOPO compound); 0 (EG-DOPO compound); 0 (ETA-DOPO compound); 0 (Flame Retardants); 0 (Organophosphorus Compounds) |
| Entry Date(s): | Date Created: 20160302 Date Completed: 20170307 Latest Revision: 20181113 |
| Update Code: | 20260130 |
| PubMed Central ID: | PMC5225203 |
| DOI: | 10.1007/s00204-016-1680-4 |
| PMID: | 26928308 |
| Database: | MEDLINE |
Journal Article