Propionic acid, sodium propionate, and calcium propinate have demonstrated low acute toxicity after oral administration to mice or rats. The adverse effects observed in chicken embryos occurred only after injection of large amounts of calcium propionate or sodium propionate into the yolk sac, and the reversions observed in a host-mediated assay of calcium propionate were unrelated to dose. These results in chickenembryos and the host-mediated assay must be viewed in the light of other microbial assays and animal studies that demonstrate no adverse effects and the fact that propionate is a normal intermediary metabolite. Microbial assays for mutagenicity of propionic acid and calcium and sodium propionate were negative. Investigations of the teratogenicity of calcium propionate in four mammalian systems also were negative. Short-term feeding tests show the most sensitive animals tested, young and vitamin B12- deficient animals, experience adverse effects on weight gain only when propionate intakes are many orders of magnitude greater than the estimate of human dietary intake of propionate used as a food ingredient, about 1 mg per kg per day. Long-term feeding studies of propionic acid and calcium propionate have not been reported. However, a long-term feeding study of sodium propionate showed no adverse effects in rats.