Orotic acid salts as sources of orotic acid and various minerals added for nutritional purposes to food supplements

Abstract

The petitioners have submitted only few data concerning the toxicity of orotic acid and none on the salts. Orotic acid has a low acute toxicity. In repeated doses orotic acid induces fatty livers in the rat, but not in other species tested. No data were submitted on reproductive and \ndevelopmental toxicity and only irrelevant data on genotoxicity. \nSeveral studies have shown that repeated dosing of orotic acid to rats and some other species promotes the formation of tumours initiated by various known carcinogenic substances. The usual concentration to promote tumours has been 1 % in the diet, but also 0.5 and 0.2 % in the diet has been shown to have promoting effect, while 0.1 % in the diet did not have effect within the time span tested (up to 20 weeks). A No Observed Adverse Effect Level for this effect can thus be determined to be 50 mg/kg bw/day, while the Lowest Observed Effect \nLevel is 100 mg/kg bw/day. In a long-term feeding study in rats, 1 % orotic acid in the diet without any initiation, increased the frequency of tumours likely due to a promoting effect of orotic acid on \nspontaneously arising and/or diet induced altered cells. Orotic acid salts as sources of orotic acid and various minerals added for nutritional purposes to food supplements The Panel considers that it is not appropriate to conclude on the safety for a combination \nbetween chromium and a tumour promoter as long as it is not clear whether chromium is genotoxic or not. The Panel concludes that…