Decabromodiphenylether (deca-BDE) and triclosan (2,4,4'-trichloro-2'-hydroxydiphenylether) are used in consumer products as flame retardant and bactericide, respectively. Dermal contact is a major human exposure pathway. Deca-BDE and triclosan are known to be photolytically degraded to compounds like lower-BDEs and dioxins. My hypothesis is that photolysis of deca-BDE and triclosan generates free radicals and degradation products which cause toxic effects including cytotoxicity, growth inhibition, oxidative stress and genotoxicity in skin. To test this hypothesis radical formation and photolytic products of deca-BDE and toxic effects of deca-BDE and triclosan alone/with UV-exposure were determined using immortal human keratinocytes (HaCaT) and primary human skin fibroblasts (HSF).
My electron paramagnetic resonance and GC-MS studies indicate that deca-BDE is photoreactive and UV irradiation of deca-BDE in organic solvents generates free radicals and lower-BDEs. The free radical formation is wavelength-dependent and positively related to the irradiation time and deca-BDE concentration.
In structure-activity relationship studies with deca-BDE, octa-BDE, PBB 209, PCB 209 and diphenyl ether, the presence of halogen atoms (Br > Cl), and/or an ether bond enhance free radical formation. Debromination and hydrogen abstraction from the solvents are the mechanism of radical formation with deca-BDE, which raises concerns about possible toxic effects in UV-exposed skin.
In cell culture experiments high levels of triclosan plus UV irradiation and repetitive deca-BDE and UV exposures caused synergistic cytotoxicity in HaCaT. However, neither triclosan nor deca-BDE can be regarded as a phototoxicant following the OECD test and evaluation guidelines. In HSF, no synergistic cytotoxicity was observed, although HSF were more sensitive to deca-BDE and triclosan alone than HaCaT. Contrary to expectations, the photodegradation products of triclosan were less toxic than triclosan itself to HaCaT. However, UV irradiation of triclosan-exposed cells produced a dose dependent increase in intracellular oxidative stress (dichlorofluorescein formation). Comet experiments did not show consistent results of genotoxicity in HaCaT. Overall, deca-BDE and triclosan had no or weak phototoxic potential in cells with the experimental conditions employed.
To my knowledge, my research is the first prove of free radical formation during UV irradiation of deca-BDE and the first investigation of phototoxicity of deca-BDE and triclosan in human skin cells.
| Identifer | oai:union.ndltd.org:uiowa.edu/oai:ir.uiowa.edu:etd-2077 |
| Date | 01 December 2010 |
| Creators | Suh, Yang-Won |
| Contributors | Ludewig, Gabriele |
| Publisher | University of Iowa |
| Source Sets | University of Iowa |
| Language | English |
| Detected Language | English |
| Type | dissertation |
| Format | application/pdf |
| Source | Theses and Dissertations |
| Rights | Copyright 2010 Yang-Won Suh |
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