FAO Nutrition Meetings Report Series No. 40A,B,C WHO/Food Add./67.29 TOXICOLOGICAL EVALUATION OF SOME ANTIMICROBIALS, ANTIOXIDANTS, EMULSIFIERS, STABILIZERS, FLOUR-TREATMENT AGENTS, ACIDS AND BASES The content of this document is the result of the deliberations of the Joint FAO/WHO Expert Committee on Food Additives which met at Rome, 13-20 December, 19651 Geneva, 11-18 October, 19662 1 Ninth Report of the Joint FAO/WHO Expert Committee on Food Additives, FAO Nutrition Meetings Report Series, 1966 No. 40; Wld Hlth Org. techn. Rep. Ser., 1966, 339 2 Tenth Report of the Joint FAO/WHO Expert Committee on Food Additives, FAO Nutrition Meetings Report Series, 1967, in press; Food and Agriculture Organization of the United Nations World Health Organization 1967 DIACETYLTARTARIC ACID AND FATTY ACID ESTERS OF GLYCEROL Synonyms Diacetyl tartaric acid esters of mono- and diglycerides; Tartaric acid esters, diacetylated, of mono- and diglycerides Chemical description This product consists of mixed glycerol esters of fatty acids and diacetyl tartaric acid. Structural formula Major components are: I. CH2-OR CH-OCO-CH(OCO-CH3)-CH(OCO-CH3)-COOH CH2-OCO-CH(OCO-CH3)-CH(OCO-CH3)-COOH II. CH2-OR ' CH-OR ' CH2-OCO-CH(OCO-CH3)-CH(OCO-CH3)-COOH III. CH2-OR ' CH-OCO-CH(OCO-CH3)-CH(OCO-CH3)-COOH ' CH2-OR where R represents various saturated and unsaturated fatty acid moiety or hydrogen in II or III. Definition The product consists of esters made by the interaction of diacetyl tartaric anhydride with monoglycerides, or with mono-diglyceride mixture made from edible oils, fats or fatty acids therefrom. The material appearing in commerce often consists of mixtures of the product described above with mono-and diglycerides. Description The esters range in appearance from sticky, viscous liquids through a fat-like consistency to yellow waxes which hydrolyse in moist air to liberate acetic acid. Uses As emulsifier. Biological Data Biochemical aspects Six male rats ware fed 0.53-0.81 g/kg body-weight 14C-acetyltartaric acid ester of none-and diglycerides (labelled in the two carboxyl groups of tartaric acid) as an oily solution. Within 24 hours only 26-31 per cent. of the radioactivity was absorbed. Twelve to twenty per cent. of the radioactivity was eliminated as 14CO2 and 8-13 per cent. was excreted in the urine; 2 per cent. was found in the carcass (Lang & Schmidt, 1965). The analysis of the depot fat of dogs fed up to 20 per cent. of the substance for 22 months showed no traces or either free or a fat soluble derivative of tartaric acid (Koppanyi & Dardin, 1950). The digestibility coefficient was over 90 per cent. of the substance or about the same as that of lard (Koppanyi & Dardin, 1950). In an aqueous medium diacetyl tartaric ester of mono- and diglycerides was hydrolysed spontaneously to mono- and diglycerides and acetylated tartaric acid, the hydrolysis being somewhat accelerated by pancreatic lipase (Lang & Schmidt, 1965). There was some evidence that diacetyltartaric acid was also hydrolysed in the body (Sourkes & Koppanyi, 1950). Acute toxicity No acute toxic effects at a practicable dose level have been demonstrated. Rats and rabbits tolerated intragastric doses of 30 g/kg body-weight and dogs 27 g/kg body-weight without any adverse effects. No diarrhoea was noted and autopsied animals showed no pathological changes. Histological examination of liver and kidneys of animals killed 10 days after the administration of the substance showed no abnormalities (Koppanyi & Dardin, 1950). Short-term studies Dog. Thirteen dogs each received daily i.v. injections of 0.5 per cent. suspensions of the substance in isotonic glucose at a dose rate of 40-50 ml/kg body-weight for a total of up to 30 infusions. A fall in haemoglobin concentration occurred in 11 dogs and a pleural effusion in 6. Groups of 2 three-year old dogs were fed diets containing 0, 5, 10 and 20 per cent. of diacetyl tartaric esters of mono- and diglycerides for 25-1/2 months. No specific effects attributable to the test substance were seen (Hartwig et al., 1962). Long-term studies Rat. Groups of 8 rats were fed 0, 5, 10 and 20 per cent. diacetyltartaric esters of mono- and diglycerides, another 2 groups were fed 50 per cent. white bread (broad control group) and 50 per cent. bread which was baked with the addition or 10 per cent. of the emulsifier in terms of flour weight (bread test group) for two years. No difference was found between the groups regarding body-weight, external appearance, liver and kidney weights and mortality rate. Autopsies and histological examination of the major organs showed no changes attributable to the test substance. A second generation was maintained on similar regimes for 22 months. There was no difference between the groups regarding body-weight, mortality and results of gross and histological examination. All litters were normal (Koppanyi & Dardin, 1950). Comments Diacetyltartaric acid is not a natural consistuent of the diet, and its rate of spontaneous hydrolysis possibly allows the absorption of some unhydrolyzed compound. The experimental results show that the ester has a very low toxicity when given orally and that the acetylated tartaric acid moiety is absorbed only to a small extent. Evaluation is based on the available toxicological information rather than the results of the biochemical and metabolic studies. Evaluation Level causing no toxicological effect Rat. 100 000 ppm in the diet, equivalent to 5000 mg/kg body-weight/day. Estimate of acceptable daily intakes for man mg/kg body-weight Unconditional acceptance1 0-25 Conditional acceptance 25-50 REFERENCES FAO/WHO (1965) FAO Nutrition Meetings Report Series No. 38; Wld Hlth Org. techn. Rep. Ser., 309 Hartwig, Q. L., Singleton, W. S. & Cotlar, A. M. (1962) Toxicol. Appl. Pharmacol., 4, 107 Koppanyi, T. &, Dardin, V. (1950) Unpublished report to WHO Lang, K. & Schmidt, B. (1967) In press Sourkes, T, L. & Koppanyi, T. (1950) J. Amer. Pharm. Assoc., sci. Ed., 39, 275 1 The total food additive intake of tartaric acid should not exceed 6-20 mg/kg body-weight/day (FAO/WHO, 1965).
See Also: Toxicological Abbreviations