Comparative ability of various PCBs, PCDFs, and TCDD to induce cytochrome P450 1A1 and 1A2 activity following 4 weeks of treatment.
Toxic equivalency factors (TEFs) have been proposed for dibenzo-p-dioxins, dibenzofurans, and polyhalogenated biphenyls. The proposed toxic equivalency factors (TEFs), which are presently being evaluated in our laboratory, are currently used to estimate the potential health risk associated with exposure to complex mixtures containing these chemicals. In preliminary studies, equally potent doses, based on the published TEFs and relative enzyme-inducing potency, of 2,3,7,8-tetrachloro-dibenzo-p-dioxin (TCDD), 2,3,7,8-tetrachlorodibenzofuran, 1,2,3,7,8-pentachlorodibenzofuran, 1,2,3,4,6,7,8,9-octachloro-dibenzofuran, 3,4,3',4'-tetrachlorobiphenyl, 2,3,4,3',4'-pentachlorobiphenyl, 3,4,5,3',4'-pentachlorobiphenyl, 2,3,4,3',4',5'-hexachlorobiphenyl, 2,3,4,5,3',4'-hexachlorobiphenyl, and 3,4,5,3',4',5'-hexachlorobiphenyl were administered to female B6C3F1 mice 5 days a week over a 4-week period. Hepatic, skin, and lung cytochrome P450 1A1 and hepatic 1A2 activities were determined for all chemicals tested and compared to those from TCDD-treated mice. These initial studies indicate that the present TEFs do not reliably predict induction potency for many of the chemicals. Furthermore, our data suggest that the relative inductive potency of these chemicals may be tissue specific and that estimates of TEFs based on hepatic ethoxyresorufin O-de-ethylase activity may not accurately reflect the potency of these chemicals in nonhepatic tissue. The TEFs proposed for the "dioxin-like" polychlorinated biphenyls (PCBs) overestimate the potency of these compounds by factors of 10-1000. The present study indicates that more experimental data are required before TEFs for PCBs should be used in regulatory decision making.
De Vito
M J
MJ
Center for Environmental Medicine, University of North Carolina, Chapel Hill 27599.
Maier
W E
WE
Diliberto
J J
JJ
Birnbaum
L S
LS
D000818:Animals; D001189:Aryl Hydrocarbon Hydroxylases / Q000096:biosynthesis; D001572:Benzofurans / Q000633:toxicity*; D019363:Cytochrome P-450 CYP1A1; D003577:Cytochrome P-450 Enzyme System / Q000096:biosynthesis*; D004790:Enzyme Induction / Q000187:drug effects; D005260:Female; D051379:Mice; D008815:Mice, Inbred Strains; D008861:Microsomes / Q000187:drug effects / Q000201:enzymology; D008862:Microsomes, Liver / Q000187:drug effects / Q000201:enzymology; D010088:Oxidoreductases / Q000096:biosynthesis; D011078:Polychlorinated Biphenyls / Q000633:toxicity*; D000072317:Polychlorinated Dibenzodioxins / Q000633:toxicity*; D011108:Polymers / Q000633:toxicity*; D012867:Skin / Q000187:drug effects / Q000201:enzymology / Q000648:ultrastructure
D001572:Benzofurans; D000072317:Polychlorinated Dibenzodioxins; D011108:Polymers; C016068:polychlorodibenzofuran; D003577:Cytochrome P-450 Enzyme System; D011078:Polychlorinated Biphenyls; D010088:Oxidoreductases; D001189:Aryl Hydrocarbon Hydroxylases; D019363:Cytochrome P-450 CYP1A1; C023738:acetanilide hydroxylase