Forestomach carcinogens: pathology and relevance to man

Squamous cell carcinomas of the forestomach have been observed in many carcinogenicity studies in rodents, especially after oral or gavage exposure. The histopathological diagnosis of forestomach lesions and the relevance of the data for human risk estimation can be controversial. The pathological classification may be troublesome because of the low-grade malignancy and the pseudoepitheliomatous hyperplasia that may develop after ulceration and inflammation. For human risk estimation it is important to understand the mechanism of action; this is illustrated by examples using butylated hydroxyanisole, methyl bromide, and epichlorohydrin. Another feature that complicates risk estimation is the absence of a homologue for the forestomach in man. The potential risk from non-genotoxic forestomach carcinogens in man involves exposure of the mouth, pharynx, and esophagus at dose levels that exert irritating action. It is assumed that exposure to non-genotoxic chemicals at concentrations far below those having irritating potential is not hazardous to humans.