Relative differences in aryl hydrocarbon receptor-mediated response for 18 polybrominated and mixed halogenated dibenzo-p-dioxins and -furans in cell lines from four different species.
As a consequence of ubiquitous use of brominated organic chemicals, there is a concern for persistent or increasing environmental levels of polybrominated dibenzo-p-dioxins/furans (PBDD/Fs) and mixed polychlorinated and polybrominated dibenzo-p-dioxins/furans (PXDD/Fs). Hence, there is a need to broaden the toxicological and environmental knowledge about these compounds, as a basis for risk assessment. In the study presented here, the relative potencies (REPs) for 18 PBDD/F and PXDD/ F congeners were determined in four dioxin-specific bioassays from different species: dioxin receptor chemically activated luciferase expression assay (DR-CALUX, rat hepatoma cells), TV101L (human hepatoma cells), and GPC.2D (guinea pig adenoma cells), as well as ethoxyresorufin-O-deethylase induction in the fish cell line RTL-W1 (rainbow trout liver cells). The bioassay specific REP factors presented here enable the assessment of the contribution from PBDD/Fs and PXDD/Fs to total 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) equivalents (TEQs: toxic equivalents), using bioassay analysis. The PBDD/Fs were found to be equally potent as their chlorinated analogues in the three mammalian assays, whereas the PXDD/Fs showed relatively higher potencies. Of special concern were the 2,3,7,8-substituted penta- and tetrahalogenated congeners, for which mean REPs were > or =1. The 2-B-1,3,7,8-CDD (2-bromo-1,3,7,8-tetrachlorodibenzo-p-dioxin) was up to three times more potent than TCDD in individual experiments (on weight basis). The RTL-W1 was less sensitive to the tested compounds with overall 10-fold lower REPs than the mammalian cell lines. Although the REP factors exhibited species-specific differences, overall resembling rank orders of dioxin-like potency were obtained.
Olsman
Helena
H
Man-Technology-Environment Research Centre (MTM), Department of Natural Science, University of Orebro, Orebro, Sweden.
Engwall
Magnus
M
Kammann
Ulrike
U
Klempt
Martin
M
Otte
Jens
J
Bavel
Bert van
Bv
Hollert
Henner
H
D000236:Adenoma / Q000473:pathology; D000818:Animals; D001681:Biological Assay; D002460:Cell Line; D004147:Dioxins / Q000633:toxicity*; D004785:Environmental Pollutants / Q000633:toxicity*; D005663:Furans / Q000633:toxicity*; D006168:Guinea Pigs; D006801:Humans; D006842:Hydrocarbons, Brominated / Q000633:toxicity; D006846:Hydrocarbons, Halogenated / Q000633:toxicity*; D008099:Liver / Q000187:drug effects* / Q000473:pathology; D017686:Oncorhynchus mykiss; D000072317:Polychlorinated Dibenzodioxins / Q000633:toxicity; D051381:Rats; D018336:Receptors, Aryl Hydrocarbon / Q000378:metabolism*; D018570:Risk Assessment
D004147:Dioxins; D004785:Environmental Pollutants; D005663:Furans; D006842:Hydrocarbons, Brominated; D006846:Hydrocarbons, Halogenated; D000072317:Polychlorinated Dibenzodioxins; D018336:Receptors, Aryl Hydrocarbon; C020887:dibenzo(1,4)dioxin