Propionic acid and the phenomenon of rodent forestomach tumorigenesis: a review.

Propionic acid (PA) is widely used as an antifungal agent in food. It is present naturally at low levels in dairy products and occurs ubiquitously, together with other short-chain fatty acids (SCFA), in the gastro-intestinal tract of humans and other mammals as an end-product of the microbial digestion of carbohydrates. It has significant physiological activity in animals. PA is irritant but produces no acute systemic effects and has no demonstrable genotoxic potential. Rats receiving PA at 4% in the diet develop hyperplastic lesions and tumours of the forestomach. Such changes are also reported to have been produced by a variety of other chemicals, mechanical and chemical irritants, parasites, and even various dietary insufficiencies or imbalances. Evidence suggests that repeated or persistent damage to cells of the forestomach epithelium and associated proliferative responses may be a common factor in rodent forestomach tumorigenesis. Although humans do not have a forestomach, the mouth, pharynx and oesophagus are lined with similar epithelium and thus are potential target organs. However, food contact time is considerably less in these organs than in the rodent forestomach. On current evidence, PA cannot be considered a carcinogenic risk to humans; nevertheless, to determine a safe level of dietary exposure it is suggested that no-observable-effect levels should be determined for epithelial cell damage and proliferative responses in the squamous mucosa of laboratory animals, particularly in those parts of the gastro-intestinal tract having a counterpart in humans, such as the pharynx and oesophagus.