Effects of pentachlorophenol on hepatic drug-metabolizing enzymes and porphyria related to contamination with chlorinated dibenzo-p-dioxins and dibenzofurans

The hepatic effects of technical and pure grade pentachlorophenol were investigated in female rats fed 20, 100 and 500 ppm of each for 8 months. Technical pentachlorophenol was contaminated with 8 ppm hexa-, 520 ppm hepta-, and 1380 ppm octachlorodibenzodioxtns and with 4 ppm tetra-, 42 ppm penta-, 90 ppm hexa-, 1500 ppm hepta- and 200 ppm octachlorodibenzofurans; pure pentachlorophenol contained less than 0.1 ppm of each of these contaminants. Technical pentachlorophenol produced hepatic porphyria and increased hepatic aryl hydrocarbon hydroxylase activity, glucuronyl transferase activity, liver weight, cytochrome P-450 and microsomal heme, but not N-demethylase activity. The peak of the CO-difference spectrum of cytochrome P-450 was shifted to 448 nm, and there was a dramatic increase in the 455-430 ratios of the ethyl isocyanide difference spectrum. The enzyme changes were observed at 20 ppm of technical pentachlorophenol. Porphyria occurred at 100 and 500 ppm. Pure pentachlorophenol had no significant effect on aryl hydrocarbon hydroxylase activity, liver weight, cytochrome P-450, microsomal heme, the ethyl isocyanide difference spectrum or N-demethylase activity at any dose level, but did increase glucuronyl transferase at 500 ppm. In contrast, both pure and technical pentachlorophenol decreased body weight gain comparably at 500 ppm. It is concluded that technical pentachlorophenol produces a number of liver changes which cannot be attributed to pentachlorophenol itself, but are consistent with the effects of biologically active chlorinated dibenzo-p-dioxins and dibenzofurans.