Toxicological evaluation of some food additives including anticaking agents, antimicrobials, antioxidants, emulsifiers and thickening agents WHO FOOD ADDITIVES SERIES NO. 5 The evaluations contained in this publication were prepared by the Joint FAO/WHO Expert Committee on Food Additives which met in Geneva, 25 June - 4 July 19731 World Health Organization Geneva 1974 1 Seventeenth Report of the Joint FAO/WHO Expert Committee on Food Additives, Wld Hlth Org. techn. Rep. Ser., 1974, No. 539; FAO Nutrition Meetings Report Series, 1974, No. 53. ESTERS OF GLYCEROL AND THERMALLY OXIDIZED SOYBEAN FATTY ACIDS Explanation These substances have been evaluated for acceptable daily intake by the Joint FAO/WHO Expert Committee on Food Additives (see Annex 1, Ref. No. 27) in 1971. Since the previous evaluation, additional data have become available and are summarized and discussed in the following monograph. The previously published monograph has been expanded and is reproduced in its entirety below. BIOLOGICAL DATA* BIOCHEMICAL ASPECTS Groups of five male and five female rats received in their diet either 20% soybean oil or thermally oxidized material. Highly modified material reduced the absorption of dietary fat in proportion to the degree of modification introduced. Modified material delays absorption of oil from the gastrointestinal tract as measured by residuals found in the gut. Similar delaying effects have been demonstrated on the presence of chylomicrons and fat in the intestinal lymph fluid. The passage of intestinal contents is delayed if modified oil is administered. Compared with normal oil there is an early increase followed by only slight decrease in bile flow following oral administration of modified oil. Intraperitoneal administration of modified oil increases the diuretic effect of normal soybean oil when given intraperitoneally. Study of the liver function after eight weeks feeding of modified oil showed retention of the bromosulphophthalein used as indicator compared with normal oil (Kieckebusch et al., 1962). The in vitro effect of modified oil on the kinetics of various cellular enzyme systems showed generally no inhibition of oxidative metabolism (Kieckebusch et al., 1962). TOXICOLOGICAL STUDIES Acute toxicity None available. * It should be noted that some of the studies refer to the unesterified thermally oxidized oils. Short-term studies Rat Groups of 20 male and 20 female rats received over 12 to 16 weeks in their diet either 20% untreated soybean oil of 5% variously modified soybean oil plus 15% olive oil or 2.5% modified oil plus 17.5% olive oil. Only highly modified oils showed significant reduction in growth, food intake and increased mortality. No definite effect was noted at the 2.5% level. Motor activity of animals on high doses of highly modified oil was increased compared with controls. The weights of major organs were similarly increased for the groups on the more highly modified oils. Gross and histopathology showed some pathological changes in the thyroid and kidney of the group receiving the most highly modified material (Kieckebusch et al., 1962). Three groups each of six rats were treated for 17 weeks with an esterified product at 0, 0.084 and 0.84% of their basic diet. There was no significant effect on weight gain and macroscopic appearance. Liver and stomach were examined histologically and found to be normal (Dam, 1952). Two groups of nine male rats received for 36 weeks feeds containing margarine made with an esterified product at 0.3 and 3% levels. No controls were used. No weight differences or gross pathological changes were noted. The histology of kidneys, liver and small intestine was normal (Aaes-Jorgensen et al., 1954). Pig Four groups of four female pigs received an esterified product for 98 days at dietary levels of 0, 0.4, 2 and 10%. No significant effects were discovered on growth rate, food consumption, blood picture, liver and kidney function, serum chemistry, organ weights, gross and histopathology due to administration of the test compound (Gyrd-Hansen & Rasmussen, 1968). Long-term studies Rat A three generation study was performed using an average level of 15% esterified product in the diet. The P generation (57 females, 15 males) was observed for at least 24 months. Growth, body weight gain and appearance were similar to controls (seven male, seven female) receiving 15% soybean oil. Five animals in the test group developed tumours but none in the control group. There were 16 survivors in the test group and two in the control group. The F1 generation (37 male, 37 female) was also observed for 24 months. Thirty-seven males and females received soybean oil as controls. Twenty-four test and 10 control animals survived two years. Two test-animals and three controls developed tumours. The F2 generation (57 female, 27 male) was observed for over two years. Seventy males and females acted as controls on soybean oil. Four test and 19 control animals survived 24 months. No animal in the test group but three in the control group developed tumours. Both the F1 and F2 generation showed no significant differences from controls as regards growth, body weight gain, gross and histopathology. In another experiment an esterified product was fed orally at the rate of 3 g/day and injected s.c. to 29 rats at 1 ml weekly for five months and 2 ml bi-weekly for a further three months. Animals were observed for 27 months. No tumours developed. A control series of 30 rats treated similarly with oral esterified product and injected s.c. with refined soybean oil showed four tumours after 24 months observation, none at the site of injection. The F1 test generation (nine male, nine female) received 3 g esterified product orally and 1 ml i.p. for eight weeks, followed by a further 1 ml i.p. for four months. After 11 months six survived without any tumours being noted. The control group (14 male, four female) received 1 ml soybean oil s.c. for five months and 2 ml s.c. for three months. During 29 months observation, one rat developed a tumour at the site of injection (Harmsen, 1959, 1960, 1961). Rats fed with 20% of thermally oxidized soybean oil in the diet had a significantly longer life-span (807 ± 32 days) than those fed with 20% of fresh soybean oil (673 ± 42 (mean ± S.E.)): a similar difference was observed between other oxidized and fresh fats and oils (Kaunitz et al., 1966). Comments: No adequate specification has been provided for this material. It has not been possible to relate the available toxicological information to the materials in commercial use. EVALUATION Not possible on the data provided. * Previously allocated ADI is withdrawn. REFERENCES Aaes-Jorgensen, E. et al. (1954) Unpublished report supplied by Grindstedvaerket Laboratoriet Dam, H. (1952) Unpublished report submitted by Grindstedvaerket Laboratoriet Gyrd-Hansen, N. & Rasmussen, F. (1968) Fd. Cosmet. Toxicol., 6, 163 Harmsen, H. (1959) Unpublished report submitted by Grindstedvaerket Laboratoriet Harmsen, H. (1960) Unpublished report submitted by Grindstedvaerket Laboratoriet Harmsen, H. (1961) Unpublished report submitted by Grindstedvaerket Laboratoriet Kaunitz, H., Johnson, R. E. & Pegus, L. (1966) Proc. Soc. exptl. Biol. Med., 123, 204 Kieckebusch, K. et al. (1962) Fette, Seifen, Anstrichmittel, 64, 1154
See Also: Toxicological Abbreviations