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 ACETIC ACID, GLACIAL Chemical name Acetic acid Empirical formula C2H4O2 Structural formula CH3COOH Molecular weight 60.05 Definition Glacial acetic acid contains not less than 99.0 per cent. C2H4O2. Description A colourless liquid or crystalline solid, having a pungent characteristic odour and, when well diluted with water, an acid taste. Uses As acidifier, flavouring agent, for the prevention of rope in baking and as a solvent. Biological Data Biochemical aspects Acetate enters naturally into the metabolism of the body. It is absorbed from the gastrointestinal tract and through the lungs and almost completely oxidized by tissues. The metabolic pathways are reasonably well-known and involve the formation of ketone bodies. Isotope experiments have shown the various C atoms to be utilized in the formation of glycogen, intermediates of carbohydrates and fatty acid synthesis as well as cholesterol synthesis. In addition it participates in the acetylation of amines and formation of proteins of plasma, liver, kidney, gut mucosa, muscle and brain (von Oettingen, 1960). Acute toxicity Animal Route LD50) References (mg/kg body-weight) Mouse oral 4 960 Woodard et al., (free acid) 1941 Rat oral 3 310 Woodard et al., (free acid) 1941 oral 3 530 Smyth, 1951 (sod. acetate) Rabbit rectal 1 200 Dreyfus, 1920 (free acid) (LD, 1 hour) s.c. 1 200 Dreyfus, 1920 (free acid) (LD, 48 hours) oral 1 200 Dreyfus, 1920 (free acid) (LD, 6 days) Toxic effects of acetic acid are due to its irritant properties as well as its effect on the central nervous system and kidneys. Large oral doses causes narcotic C.N.S. depression and death in rats and mice (Woodard et al., 1941). Short-term studies Rat. Groups of 3-6 rats were given 0.01, 0.1, 0.25 and 0.5 per cent. acetic acid in drinking water for periods of from 9-15 weeks. fluid intake was the same in all groups; at the 0.5 per cent. level there was immediate progressive reduction in body-weight gain, loss of appetite and fall in food consumption to 27 per cent. Mortality rate was unaffected (Sollmann, 1921). In another experiment groups of 3-4 rats survived 14 days when given 1800 mg/kg body-weight/day free acid intragastrically or 4200-4800 mg/kg body-weight sodium acetate, but only 3-5 days on daily intragastric 2400. mg/kg body-weight free acid. Animals lost weight before death and showed blistered paws and reddened noses. No autopsies were done (Hemmingway & Sparrow, 1942). Intragastric intubation of 3 ml of 10 per cent. solution acetic acid to rats for 90 days produced a drop in haemoglobin concentration and erythrocyte count (Wysokinska, 1952). Swine. Four groups of 2 young pigs were fed daily diets containing 0, 240, 720, 960 and 1200 mg/kg body-weight/day for successive 30-day periods to a total of 150 days. There were no significant differences in growth rate, weight gain, early morning urinary ammonia and terminal blood pH between controls and test groups. No autopsies were done (Lamb & Evvard, 1919). Long-term studies No animal studies are available. About 1 g/day of acetic acid present in vinegar and other items of food and drink has been consumed by man for centuries apparently without causing any adverse effects. However, continued ingestion of large doses has been regarded as a contributory factor in the development of Laennec type of liver cirrhosis (Singer, 1936). Comments Acetic acid has a sufficiently acid taste to limit the amount used in foods. Human studies determining the maximum metabolic load of acetate are not available. In evaluating the acceptance of acetic acid, emphasis is placed on its established metabolic pathways and its normal consumption by man. Evaluation For purposes of evaluation all sources of acetate used as food additives should be considered together. Since acetic acid has a sufficiently acid taste to limit the amount used in foods, it is not necessary to indicate acceptable daily intakes for man. REFERENCES Dreyfus, L. (1920) Compt. rend. soc. biol., 83, 136 Hemmingway, A. & Sparrow, A. (1942) Proc. Soc. exper. Biol. Med., 51, 44 Lamb, A. R. & Evvard, M. J. (1919) J. Biol. Chem., 37, 317 von Oettingen, W. F. (1960) Arch. Ind. Health, 21, 28 Singer, L. (1936) Munch. med. Wschr., 83, 1288 Sollmann, T. (1921) J. Pharm. Exp Therap., 16, 463 Woodard, G., Lange, S. W., Nelson, K. W. & Calvery, H. O. (1941) J. Ind. Hyg. Toxic., 23, 78 Wysokinska, Z. (1952) Roczniki Panstwowego Zakladu Hig., 3, 273
See Also: Toxicological Abbreviations Acetic acid (ICSC) ACETIC ACID (JECFA Evaluation)