Differences in acute toxicity syndromes of 2,3,7,8-tetrachlorodibenzo-p-dioxin and 1,2,3,4,7,8-hexachlorodibenzo-p-dioxin in rats

摘要: Abstract 2,3,7,8-Tetrachlorodibenzo-p-dioxin (TCDD) is the most potent congener of polychlorinated dibenzo-p-dioxins. The potency 1,2,3,4,7,8-hexachlorodibenzo-p-dioxin (HxCDD) only 10% that TCDD for typical aryl hydrocarbon receptor (AHR)-mediated effects. Acute lethality, macroscopic effects, and liver toxicity HxCDD were compared in male rats strain Han/Wistar (Kuopio; H/W), lines A B. latter two rat originate from crossbreeding H/W Long-Evans (Turku/AB) rats. line are highly resistant to acute due an altered AHR, while B moderately H/W-type alleles another, yet unidentified gene contributing resistance (“gene B”). received 200–10,000 μg/kg either or intragastrically monitored 46 days. In all rats, highest dose (10,000 μg/kg) reduced body weight more effectively than identical TCDD. Only caused gastrointestinal hemorrhage, pale (fatty) livers death by day 15 pronounced hepatic fatty degeneration, whereas induced accumulation biliverdin its derivatives. Both congeners sinusoidal distension liver. estimated LD50 values >10,000 μg/kg 2000–10,000 μg/kg HxCDD, respectively; they 480 μg/kg 1000–2000 μg/kg, respectively. Thus, was inducing mortality contrary what predicted toxic equivalency factor (TEF) values. B, expected rank order potencies prevailed. These findings suggest addition canonical AHR-mediated pathways, possesses AHR-independent mechanism toxicity, whose main manifestations rapid loss, mortality, hemorrhage.