Dose–Response Relationships for Induction of CYP1A1 and CYP1A2 Enzyme Activity in Liver, Lung, and Skin in Female Mice Following Subchronic Exposure to Polychlorinated Biphenyls

• Published in: Toxicology and applied pharmacology 2000-09, Vol.167 (3), p.157-172
• Main Authors: DeVito, Michael J., Ménache, Margaret G., Diliberto, Janet J., Ross, David G., Birnbaum, Linda S.
• Format: Article
• Language: English
• Subjects: Animals; Biological and medical sciences; Body Weight; Chemical and industrial products toxicology. Toxic occupational diseases; CYP1A1 protein; CYP1A2 protein; Cytochrome P-450 CYP1A1 - biosynthesis; Cytochrome P-450 CYP1A2 - biosynthesis; dioxins; Dose-Response Relationship, Drug; Environmental Pollutants - toxicity; Enzyme Induction; Female; Liver - drug effects; Liver - enzymology; Lung - drug effects; Lung - enzymology; Medical sciences; Mice; Mice, Inbred Strains; Organ Size; polychlorinated biphenyls; Polychlorinated Biphenyls - toxicity; Polychlorinated Dibenzodioxins - toxicity; relative potency; Skin - drug effects; Skin - enzymology; Toxic Equivalency Factors; Toxicology; Various organic compounds
• ISSN: 0041-008X; 1096-0333
• DOI: 10.1006/taap.2000.9010

The Toxic Equivalency Factor (TEF) method is used to estimate potential health risks associated with exposure to dioxin-like chemicals. The TEF method is a relative potency (REP) scheme that assumes dose additivity, that the chemicals produce the same response through the same mechanism, and that the REP of a chemical is equivalent for all responses. The present study estimates the REP for five PCBs with dioxin-like activity. Mice were exposed to either 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD), 2,3,3′,4,4′-pentachlorobiphenyl (105), 2,3′,4,4′,5-pentachlorobiphenyl (118), 3,3′,4,4′,5-pentachlorobiphenyl (126), or 2,3,3′,4,4′-,5-hexachlorobiphenyl (156), five days/week for 13 weeks by oral gavage in a corn oil vehicle. Three days after the last dose, animals were euthanized and the ethoxyresorufin-O-deethylase activity was determined in liver, lung, and skin. Acetanilide-4-hydroxylase activity was determined in liver. In addition, liver and skin disposition of the chemicals were determined. REPs were estimated using a statistical method previously described (DeVito et al., Toxicol. Appl. Pharmacol.147, 267–280, 1997). For any given compound, the REP generally varied by less than a factor of four across endpoints when calculated based on an administered dose. However, typically there was one response for every chemical in which the REP was different by an order of magnitude or more from the other responses. There was some evidence that the REPs may be dose-dependent. While, in general, these data support the use of a single point estimate of the REP, the issue of dose-dependency requires targeted investigation.