Inductive effect on hepatic enzymes and acute toxicity of individual polychlorinated dibenzofuran congeners in rats

Abstract

Toxicological assessment of 13 individual polychlorinated dibenzofurans (PCDFs) with varying chlorine substitutions was made in young male Wistar rats. All the 9 congeners having at least three chlorine atoms in the ring positions at 2, 3, 7 and 8, such as 1,2,7,8-, 2,3,6,7-, and 2,3,7,8-tetrachlorodibenzofurans (TCDFs), 1,2,3,7,8-, 1,2,6,7,8-, 2,3,4,7,8-pentachlorodibenzofurans (PenCDFs), 1,2,3,4,6,7- and 1,2,3,4,7,8-hexachlorodibenzofurans (HCDFs), exhibited a typical 3-methylcholanthrene (MC)-type induction, i.e., a marked increase in activity of aryl hydrocarbon hydroxylase (AHH) and DT-diaphorase in the liver. The most potent congeners were 2,3,7,8-TCDF and 2,3,4,7,8-PenCDF, both of which significantly induced the AHH and DT-diaphorase even at a single dose of 1 μg/kg. On the contrary, the congeners having two or less chlorine atoms in the lateral ring positions, such as 2,8-dichlorodibenzofuran, 1,3,6,7- and 1,3,6,8-TCDFs, and 1,2,4,6,8-PenCDF, did not show any inductive effect on these hepatic enzymes at the single dose of 5 or 10 mg/kg. All the MC-type PCDFs except for 1,2,7,8-TCDF caused a marked atrophy of the thymus and a hypertrophy of the liver in rats, while no toxic signs were observed in animals treated with the congeners lacking the MC-type inducing ability. The ranking of toxic potencies of the MC-type PCDFs coincided well with their inducing abilities. The hepatic disposition of the congeners varied markedly. For example, 2,3,7,8-TCDF and 2,3,4,7,8-PenCDF showed an equipotent toxicity, however, the hepatic concentration of PenCDF was about 20-fold higher than that of TCDF. These results clearly indicate that the acute toxicity of PCDF congeners is well correlated with their MC-type inducibility, but not with their hepatic distribution.