Comparative Ability of Various PCBs, PCDFs, and TCDD to Induce Cytochrome P450 1A1 and 1A2 Activity Following 4 Weeks of Treatment

• Published in: Fundamental and applied toxicology 1993, Vol.20 (1), p.125-130
• Main Authors: DeVito, M.J., Maier, W.E., Diliberto, J.J., Birnbaum, L.S.
• Format: Article
• Language: English
• Subjects: ACTIVIDAD ENZIMATICA; ACTIVITE ENZYMATIQUE; Animals; Aryl Hydrocarbon Hydroxylases - biosynthesis; Benzofurans - toxicity; BIFENILOS POLICLORADOS; Biological and medical sciences; COMPOSE ORGANOCHLORE; COMPUESTO ORGANICO DEL CLORO; CONTAMINANTES; Cytochrome P-450 CYP1A1; Cytochrome P-450 Enzyme System - biosynthesis; Environmental pollutants toxicology; ENZIMAS; ENZYME; Enzyme Induction - drug effects; Female; FOIE; General aspects; HIGADO; Medical sciences; METALLOPROTEINE; METALPROTEINAS; Mice; Mice, Inbred Strains; Microsomes - drug effects; Microsomes - enzymology; Microsomes, Liver - drug effects; Microsomes, Liver - enzymology; Oxidoreductases - biosynthesis; PEAU; PIEL (ANIMAL); POLLUANT; Polychlorinated Biphenyls - toxicity; Polychlorinated Dibenzodioxins - toxicity; POLYCHLORURE DE BIPHENYLE; Polymers - toxicity; POUMON; PULMONES; RATON; Skin - drug effects; Skin - enzymology; Skin - ultrastructure; SOURIS; TECHNIQUE DE PREVISION; TECNICAS DE PREDICCION; TEJIDOS ANIMALES; TISSU ANIMAL; TOXICIDAD; TOXICITE; Toxicology
• ISSN: 0272-0590; 1095-6832
• DOI: 10.1006/faat.1993.1015

Comparative Ability of Various PCBs, PCDFs, and TCDD to Induce Cytochrome P450 1A1 and 1A2 Activity Following 4 Weeks of Treatment. De Vito, M. J., Maier, W. E., Diliberto, J. J., and Birnbaum, L. S. (1993). Fundam. Appl. Toxicol. 20, 125-130. 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-tetrachlorodibenzo- p-dioxin (TCDD), 2,3,7,8-tetrachlorodibenzofuran, 1,2,3,7,8-pentachlorodibenzofuran, 1,2,3,4,6,7,8,9-octachlorodibenzofuran, 3,4,3′,4′-tetrachlorobiphenyl, 2,3,4,3′,4′-pentachlorobipbenyl, 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-deethylase 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.