Animal studies: site-of-contact effects at high doses
Long-term rat studies found changes to the stomach lining (forestomach hyperplasia) at high dietary concentrations of propionic acid. EFSA's review panel noted that humans do not have a forestomach, making this finding irrelevant to people. In dogs, irritation to the oesophagus was observed at dietary concentrations around three times higher than the highest levels permitted in food, so the margin between real exposure and any observed effect is wide.
Forestomach hyperplasia in rodents fed propionic acid at high concentrations was considered not relevant to humans because humans lack this anatomical structure.
2014AnimalEFSA ANS Panel re-evaluation of propionic acid and its salts (E 280-E 283), EFSA Journal
The no observed adverse effect level for oesophageal effects in a 90-day dog study was at a propionic acid concentration approximately three times higher than the highest concentration found in food at maximum permitted use levels.
2014AnimalEFSA ANS Panel re-evaluation of propionic acid and its salts (E 280-E 283), EFSA Journal
Propionic acid is a normal part of human metabolism
Propionic acid is produced in the human gut by bacterial fermentation of dietary fibre and is a natural intermediate in the breakdown of certain amino acids and fatty acids. The body has well-established pathways for metabolising it. Propionate from food additives contributes a small fraction of the total propionate the body handles daily from these endogenous and dietary sources.
Propionic acid is an endogenous compound formed during normal colonic fermentation and amino acid catabolism in humans, and is present in a variety of fermented foods at levels comparable to or exceeding those from additive use.
2014Regulatory reviewEFSA ANS Panel re-evaluation of propionic acid and its salts (E 280-E 283), EFSA Journal
Rodent study on metabolic effects: limited relevance
A 2019 study in mice reported that propionate, when given at high doses, triggered hormonal responses that increased appetite and raised insulin levels. The doses used were far above the amounts consumed from food additives, and the results have not been replicated in human trials at dietary exposure levels. EFSA's earlier evaluation predates this study; it has not triggered a formal re-assessment.
High-dose propionate administration in mice and ex-vivo human tissue triggered glucagon and insulin secretion via adrenergic pathways, raising questions about metabolic effects at supra-dietary doses.
2019Lab + animalTirosh et al., Cell