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 1,500 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 500 mg
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
porphyria that persisted for more than 500 to 600 days.(ABSTRACT TRUNCATED AT 250 WORDS)