Toxicological assessment of hexachlorobiphenyl isomers and 2,3,7,8-tetrachlorodibenzofuran in chicks: II. Effects on drug metabolism and porphyrin accumulation

Abstract

Pure hexachlorobiphenyl (HCB) isomers induce a number of changes in parameters of drug metabolism in the chick including changes in cytochrome P-450, liver weight, and p-nitrophenol glucuronyl transferase, but not in testosterone glucuronyl transferase activity. The most active inducers of drug metabolism were 2,3,4,2′,3′,4′-HCB and 2,4,6,2′,4′,6′-HCB, while 2,4,5,2′,4′,5′-HCB produced intermediate effects and 2,3,6,2′,3′,6′-HCB was a poor inducer. All HCBs caused uroporphyrin accumulation and increased δ-aminolevulinic acid (ALA) synthetase activity, but only 3,4,5,3′,4′,5′-HCB, 2,3,4,2′,3′,4′-HCB, and 2,4,5,2′,4′,5′-HCB produced gross accumulation of hepatic porphyrins. Tissue HCB concentrations correlated well with hepatic effects. 2,3,7,8-Tetrachlorodibenzofuran (TCDF), a contaminant of commercial polychlorinated biphenyl (PCB) mixtures, had no effects on hepatic ALA synthetase activity, porphyrin accumulation, or glucuronyl transferase. TCDF did produce a slight increase in cytochrome P-450, but the increase was smaller than that produced by HCBs. Also, the cytochrome induced by TCDF appeared qualitatively different from the cytochrome induced by TCBs, differing by a shift in the peak of the CO-difference spectrum from 450 to 449 nm and by the ratio of absorbance at 455 to 430 nm of the ethyl isocyanide difference spectrum.