Accumulation of polychlorinated dibenzo-p-dioxins and dibenzofurans in liver of control laboratory rats.
Polychlorinated dibenzo-p-dioxins (PCDDs), dibenzofurans (PCDFs), and biphenyls belong to a class of compounds, the polyhalogenated aromatic hydrocarbons (PHAHs), which are ubiquitous environmental contaminants. Due to the existence of a common mechanism of action, i.e., binding to the Ah receptor, the activity of members of this class of compounds is generally expressed relative to the prototypical 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) as toxic equivalency factors (TEFs). In the present studies we examined the presence of liver of untreated PCDFs in standard laboratory feed and in the liver of untreated rats at three different ages (60, 140, and 200 days) in terms of concentration and in toxic equivalents (TEQs, TEF x concentration). Feed was shown to contain trace amounts of PCDDs and PCDFs and control rat liver was shown to contain several PCDD and PCDF congeners in terms of concentration of congener and concentration of TEQs contributed by that congener. The total concentration of TEQs increased with increasing age in rat liver, going from 20 ppt TEQ at 60 days to 78 ppt TEQ at 200 days of age. This accumulation in dioxin-like activity was due primarily to PCDFs. In particular the congener 2,3,4,7,8-pentachlorodibenzofuran accrued in untreated rat liver accounting for approximately 80% of the total TEQ at 200 days of age. These studies affirm the pervasive presence of PHAHs and suggest prudence in evaluating chronic rat studies in which interference from background levels of PCDDs and PCDFs may be a factor.
Vanden Heuvel
J P
JP
Laboratory of Biochemical Risk Analysis, National Institute of Environmental Health Sciences, Research Triangle Park, North Carolina 27709.
Clark
G C
GC
Tritscher
A m
Am
Lucier
G W
GW
D000367:Age Factors; D000818:Animals; D001572:Benzofurans / Q000493:pharmacokinetics*; D003577:Cytochrome P-450 Enzyme System / Q000502:physiology; D000072338:Dibenzofurans, Polychlorinated; D005260:Female; D008099:Liver / Q000378:metabolism*; D000072317:Polychlorinated Dibenzodioxins / Q000031:analogs & derivatives* / Q000493:pharmacokinetics; D051381:Rats; D017207:Rats, Sprague-Dawley
D001572:Benzofurans; D000072338:Dibenzofurans, Polychlorinated; D000072317:Polychlorinated Dibenzodioxins; D003577:Cytochrome P-450 Enzyme System