Dose-response relationships in hexachlorobenzene-induced porphyria

The rate of development of hexachlorobenzene (HCB)-induced porphyria in female Wistar rats was determined using HCB dosage and porphyrin analysis protocols designed to determine factors which contribute to the delay commonly observed between initial exposure to HCB and the detection of porphyria. Measurements were made of HCB and porphyrin concentrations in the livers, kidneys, and spleens of female Wistar rats exposed continuously (up to 56 days) or for 1 day to HCB (at dietary concentrations of 1000 ppm and 100 ppm). The experiments showed that when a corn oil solution of HCB was added to the diet at a concentration of 1000 ppm, HCB accumulated rapidly in all organs, and the delay in appearance of elevated liver highly carboxylated porphyrins (HCPs) was at most 4 days (approximately 8-fold elevation of HCPs on day 4). One day of exposure to this diet was sufficient to cause elevated liver HCPs, thus showing that continuous exposure to HCB was not required to cause porphyria in this species. Solid HCB added directly to the diet (1000 ppm) resulted in less rapid HCB accumulation and less rapid development of porphyria. The experiments demonstrated that the appearance of a delay in HCB-induced porphyria in the Wistar rat is caused by the rate at which HCB is absorbed, and by using total hepatic porphyrins (rather than HCPs) as the indicator of the disorder. The experiments also showed that HCB-induced liver enlargement and neurotoxicity are not necessarily associated with the severity of porphyria.