The delay in polyhalogenated aromatic hydrocarbon-induced porphyria: mechanistic reality or methodological artefact?

Hepatic porphyria was induced in female Wistar rats exposed to dietary hexachlorobenzene (HCB) for 56 days. The well-documented several-week delay before liver total porphyrins became elevated was observed using conventional methods. However, a newly developed high-performance liquid chromatography (HPLC) technique revealed a much earlier response. Highly carboxylated porphyrins were found to increase soon after exposure to the toxicant. The long delay observed by total porphyrin analysis is shown to be due to the relatively small contribution of highly carboxylated porphyrins to the total porphyrin pool. It is concluded that the concept of a latent period is largely a methodological artefact which has confused the search for a fundamental understanding of chemically induced porphyria.