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-tetrachl orodibenzop-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 >= 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.

Ämnesord

NATURVETENSKAP  -- Kemi (hsv//swe)

NATURAL SCIENCES  -- Chemical Sciences (hsv//eng)

NATURVETENSKAP  -- Geovetenskap och miljövetenskap -- Miljövetenskap (hsv//swe)

NATURAL SCIENCES  -- Earth and Related Environmental Sciences -- Environmental Sciences (hsv//eng)

Nyckelord

Adenoma/pathology

Animals

Biological Assay

Cell Line

Dioxins/*toxicity

Environmental Pollutants/*toxicity

Furans/*toxicity

Guinea Pigs

Humans

Hydrocarbons; Brominated/toxicity

Hydrocarbons; Halogenated/*toxicity

Liver/*drug effects/pathology

Oncorhynchus mykiss

Rats

Receptors; Aryl Hydrocarbon/*metabolism

Risk Assessment

Tetrachlorodibenzodioxin/toxicity

NATURAL SCIENCES

NATURVETENSKAP

Chemistry

Kemi

Environmental chemistry

Miljökemi

Environmental toxicology

Miljötoxikologi

Miljökemi

Environmental Chemistry

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