© 1991 Oxford University Press
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Development of an Experimental Model for the Study of Hexachlorobenzene-Induced Hepatic Porphyria in the Rat1
Département de médecine du travail et d'hygiène du milieu, Faculté de médecine, Université de Montréal Québec, Canada H3C 3J7
Received October 22, 1990; accepted April 29, 1991
Development of an Experimental Model for the Study of Hexachlorobenzene-Induced Hepatic Porphyria in the Rat. KRISHNAN, K., BRODEUR, J., AND CHARBONNEAU, M. (1991). Fundam Appl. Toxicol 17, 433-441. Hexachlorobenzene (HCB) induces hepatic porphyria in rats. Various protocols of repeated cumulative and daily doses of HCB administered for several weeks until porphyria develops have been traditionally used. In order to undertake studies on early biochemical events occurring in HCB-induced porphyria, we have designed an experimental model involving the administration of a minimal amount of HCB inducing a fully developed porphyria in a well defined and predictable time frame. Groups of Sprague-Dawley rats were given (po, in 10 ml/kg of corn oil) a cumulative dose of 1500 mg HCB/kg as 50 mg/kg for 6 weeks (5 days/week) or 100 mg/kg for 3 weeks (5 days/week). In female, but not male, rats treated for 6 weeks, HCB caused a porphyria as measured by urinary uroporphyrin and hepatic porphyrin levels: this total dose given to female rats in 3 weeks was not, however, porphyrinogenic. Female rats were given 12 consecutive daily doses of 50 mg HCB/kg followed by a no-treatment period of 30 days: this cumulative dose of 600 mg HCB/kg induced a porphyria after 6 weeks. The approximate minimally effective cumulative dose inducing porphyria was determined to be 400 mg HCB/kg, regardless of the magnitude of the daily dose (25, 50, or 100 mg/kg). Finally, the administration of a cumulative dose of 500mg HCB/kg (50 mg/kg, 5 days/week for 2 weeks or 100 mg/kg/day for 5 days) induced after 5 to 6 weeks a porphyna that persisted for more than 500 to 600 days. These results suggest that induction of porphyria is dependent upon the administration of a threshold cumulative dose of HCB during an initial phase followed by a delay period with no further treatment during which full development of biochemical alterations in the heme synthesis cycle occurs.