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 POLYGLYCEROL ESTERS OF FATTY ACIDS Synonyms Polyglycerol fatty acid esters; Glyceran fatty acid esters Chemical description Mixtures of polyglycerol esters of fatty acids of food fats. Structural formula OR ' R-(OCH2-CH-CH2O)n-R Where the average value of n is no more than 3 and R is partly a fatty acid moiety or partly hydrogen radical. Definition Polyglycerol esters of fatty acids are mixtures of the esters of these fatty acids with the polyglycerol mixture. The commercial products will contain mono- and diglycerides when fats are used for transesterification with polyglycerol mixtures. Description Oleaginous substances, of a consistency depending on the fatty acids. Uses As emulsifiers. Biological Data Biochemical aspects The polyglycerol esters of fatty acids include large group of closely related compounds of complex composition. However, the individual components are found as normal constituents of the human diet, i.e. glycerol, glycerol mono-, di- and tri-fatty acid esters and individual fatty acids, with the exceptions of the artificially produced polymers of glycerol, polymers of certain fatty acids and the actual separate esters between these polymers. These latter compounds represent the toxicologically important constituents. In vitro experiments on lipase digestion of polyglycerol esters showed a slower rate of digestion than that of olive oil and the ester did not affect the lipase digestion of olive oil (Unilever Research Laboratory, 1966). Digestibility or caloric utilisation have been used to demonstrate metabolic conversion; 16 male and female rats were fed a diet containing 1 per cent. ground-nut oil and 9 per cent. polyglycerol ester or 10 per cent. ground-nut oil (as control) for 6 and 12 weeks. Polyglycerol ester as an energy source was almost equivalent to ground-nut oil, as measured by growth rate. Digestibility was calculated as 92 per cent. In another experiment rats were kept on a restricted food intake (18 calories/day) for 17 days. After realimentation with 9 per cent. polyglycerol ester and 1 per cent. ground-nut oil, no adverse effect was noted on the animals' ability to gain weight. Rats fed polyglycerol ester for 54 days as 9 per cent. of the diet showed no difference in composition of carcass fat, liver fat, liver free fatty, acids and liver phosphorus when compared with groups fed 1 per cent. or 10 per cent. ground-nut oil in the diet. Liver vitamin A levels were unaffected. A polyglycerol ester was shown to be absorbed by intestinal lymphatics, and chylomicron counts showed normal lipaemia. Suspensions in water were more slowly absorbed and reduced the rate of gastric emptying compared with ground-nut oil. The serum cholesterol level of rats was unaffected by the presence of 10 per cent. polyglycerol ester in a 42 per cent. fat diet (Unilever Research Laboratory, 1966). Acute toxicity Rat. Rats given single doses of 7, 14 and 29 g/kg body-weight of a polyglycerol eater by intubation showed no signs of any toxic effect. Repeated deals, with 10 g/kg body-weight daily over 5 days caused no deaths. Rats, injected i.p. with 1, 3 and 7 g/kg body-weight, showed no adverse effects; single doses of 10 g/kg body-weight caused some peritoneal reaction but no deaths (Unilever Research Laboratory, 1966). Rabbit. Rabbits dosed orally with 10~29 g/kg body-weight showed no toxic effects. Short-term studies Rats. Thirteen rats maintained on 9 per cent. polyglycerol ester and 1 per cent. ground-nut oil for 17 weeks showed normal kidney function (Unilever Research Laboratory, 1966). Rats kept 22 weeks on 9 per cent. PGE + 1 per cent. ground-nut oil showed no difference in weights of liver, kidney, adrenal, spleen and testes when compared with controls on 10 per cent. ground-nut oil. Gross autopsy and histological examination of liver revealed no abnormalities (Unilever Research Laboratory, 1966). Man. Thirty-seven volunteers, aged 19-24, were fed 2-20 g polyglycerol ester per day for 3 weeks in their diet. No abnormalities were detected in plasma proteins, serum amino-acids, thymol turbidity, serum bilirubin, total and free serum cholesterol, serum alkaline phosphatase, SGOT, SGPT, cholinesterase, cholesterol esterase, 24 hour urine volume, urinary creatinine, urea output, total and split faecal fat or total faecal nitrogen (Unilever Research Laboratory, 1966). Long-term studies Mouse. Groups of 25 male and 25 female mice were fed for 80 weeks on either polyglycerol ester or ground-nut oil at 5 per cent. in their diet. No adverse effect on body-weight, food consumption, peripheral blood picture and survival rate were noted. Carcass fat of the test group showed no polyglycerol residues. The levels of free fatty acids, unsaponifiable material, fatty acid composition of carcass fat and organ weights were the same in test and control groups, except for the liver and kidney weights of female mice which were significantly higher. Microscopic examination of all major organs showed nothing remarkable (Unilever Research Laboratory, 1966). Rat. A test group of 22 rats, with a control group of 28B, were kept on a diet containing 1.5 per cent. of polyglycerol ester for 3 generations and maintained for over one year without significant variation in fertility and reproductive performance. Gross and histological examination of the third generation revealed no consistent abnormality related to the test substance (Unilever Research Laboratory, 1966). In another experiment 28 male and 28 female rats were fed 5 per cent. polyglycerol ester or ground-nut oil in their diet for 2 years. No adverse effects on body-weight, food consumption, peripheral blood picture, and survival rate were noted. Liver function tests and renal function tests at 59 and 104 weeks were comparable between groups. The carcass fat contained no polyglycerol and the levels of free fatty acid, unsaponifiable residue and fatty acid composition of carcass fat were no different from controls. Organ weights, tumour incidence and tumour distribution ware similar in control and test groups. Complete histological examination of major organs showed nothing remarkable (Unilever Research Laboratory, 1966). Comments The toxicological assessment of this group of diverse but related substances is based an evaluation of satisfactory evidence for one member and assumes that alterations in the fatty acid distribution or polyglycerol content of individual members have no toxicological bearing and only affect the physical and emulsifying properties of each ester. The metabolic studies point to hydrolysis of these polyglycerol esters in the gastrointestinal tract and the utilization and digestibility studies justify the assumption that the fatty acid moiety is metabolized in the normal manner. Analytical studies have produced no evidence of cumulation of the polyglycerol moiety in body tissues. Human studies showed no adverse effects. It is desirable to have properly conducted biochemical studies on other members of this group, that do not conform to the specifications detailed above, to exclude-unforeseen effects. Evaluation Level causing no toxicological effect Rat. 50 000 ppm in the diet, equivalent to 2500 mg/kg body-weight/day. Estimate of acceptable daily intakes for man mg/kg body-weight1 Unconditional acceptance 0-12.5 Conditional acceptance 12.5-25 REFERENCES Unilever Research Laboratory (1966) Unpublished report 1 Calculated as total polyglycerol ester of palmitic acid.
See Also: Toxicological Abbreviations Polyglycerol esters of fatty acids (WHO Food Additives Series 5) POLYGLYCEROL ESTERS OF FATTY ACIDS (JECFA Evaluation)