INTERNATIONAL PROGRAMME ON CHEMICAL SAFETY WORLD HEALTH ORGANIZATION TOXICOLOGICAL EVALUATION OF SOME FOOD COLOURS, ENZYMES, FLAVOUR ENHANCERS, THICKENING AGENTS, AND CERTAIN FOOD ADDITIVES WHO FOOD ADDITIVES SERIES 6 The evaluations contained in this publication were prepared by the Joint FAO/WHO Expert Committee on Food Additives which met in Rome, 4-13 June 19741 World Health Organization Geneva 1975 1 Eighteenth Report of the Joint FAO/WHO Expert Committee on Food Additives, Wld Hlth Org. techn. Rep. Ser., 1974, No. 557. FAO Nutrition Meetings Report Series, 1974, No. 54. MICROBIAL RENNET* (Mucor miehei) Explanation This enzyme preparation has 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 No information available. TOXICOLOGICAL STUDIES Special studies on teratogenicity Rat Groups of 19 or 20 pregnant rats received either 74, 148 or 276 mg/kg agent by gavage from day 6 to 15 of pregnancy. Animals were sacrificed on day 20. No adverse effects were seen in pregnant dams. Litter parameters were unaffected except for mean pups weight which was slightly increased at the highest dose-level. The fetal anomalies observed were unrelated to administration of the test compound. No skeletal abnormalities were seen (Palmer & Lovell, 1970). Acute toxicity None available. * This enzyme preparation is prepared from the species Mucor miehei. Short-term studies Rat Four groups of 25 male and 25 female rats received in their diet 0, 0.1, 0.5 and 2.5% of microbial rennet (equivalent to 0, 100, 500 and 2500 units/kg/day) for one year. Appearance and behaviour was normal throughout the experiment. Survival was comparable in all groups and the few deaths observed were unrelated to the administration of the test substance. Mean body weight and food consumption were similar to controls. Haematology, blood chemistry and urinalysis showed nothing significant compared with controls. Relative organ weights, gross and histopathology showed nothing of note (Gesler, 1970). In another experiment groups of 20 male and 20 female rats received in their diet 0, 0.5, 1.5 and 5% of microbial rennet for one year. At the highest level of administration there was a small dose- related reduction in body weight gain in the males and in the females a slight reduction at the 1.5% level. No effect on food intake or conversion. At the 1.5% level there was very slight reduction in food intake of males only. Behaviour, appearance, urinalysis, haematology, gross and micropathology were normal (Wheldon et al., 1970). Dog Four groups of five male and five female beagles received by daily gavage six times a week for one year either 0, 500 or 2500 units/kg bw. Apart from some vomiting early in the study and occasional vomiting in the highest test group there was no further difficulty in administration. Behaviour, appearance, food consumption and mean body weight did not differ from controls. Haematology, blood chemistry, blood coagulation studies and urinalysis revealed no changes due to the administration of the test substance. Mean relative organ weights, gross and histopathology revealed no changes different from controls (Gesler, 1970a). Four groups of four male and four female beagles received 0, 5000, 15 000 or 50 000 ppm of rennet in their diet for one year. No adverse effects due to the test compound were quoted as regards mortality, appearance, body weight, ophthalmoscopy, clinical biochemistry, haematology, and urinalysis, gross and micropathology revealed nothing abnormal (Noel et al., 1970). Long-term studies Rat Groups of 20 males and 20 females received orally 100 mg/kg bw of active material for 24 months. No contemporary controls were used but reliance was placed on the known history of the colony. Conditions were not SPF and animals also received other agents and pesticides. Body weight gain was normal, six animals dying during the 24 months. Among 17 male survivors six had chronic bronchopneumonia, two had fatty liver, two had testicular atrophy and none had any tumours. Among 17 female survivors one benign fibroadenoma of the breast and one pulmonary tumour were seen. Three animals had chronic bronchopneumonia. There were other scattered lesions unrelated to treatment. One male and five females were mated and produced a normal litter of which five males and five females were treated with the agent for seven months and mated again to produce a second generation. No obvious gross abnormalities were seen (Mosinger, 1972). Comments: The available studies in two species including the long-term study in the rat reveal no adverse effects at 2.5% in the rat on 100 mg/kg bw. The levels used would have revealed any deleterious effects due to mycotoxins. This meets with the requirements laid down by the Committee. EVALUATION Acceptable daily intake not specified.* REFERENCES Gesler, R. M. (1970) Unpublished report submitted by Travenol Laboratories Inc. Gesler, R. M. (1970a) Unpublished report submitted by Travenol Laboratories Inc. Mosinger, M. (1972) Report No. 730J02 to Novo Laboratories Noel, P. R. B. et al. (1970) Report 3530/70/342 by HRC dated 20.10.1970 submitted to Novo Laboratories * The statement "ADI not specified" means that, on the basis of the available data (toxicological, biochemical, and other), the total daily intake of the substance, arising from its use or uses at the levels necessary to achieve the desired effect and from its acceptable background in food, does not, in the opinion of the Committee, represent a hazard to health. For this reason, and for the reasons stated in individual evaluations, the establishment of an acceptable daily intake (ADI) in mg per kg of body weight is not deemed necessary. Palmer, A. K. & Lovell, M. R. (1970) Report 3578/70/390 by HRC dated 6.10.70 submitted to Novo Laboratories Wheldon, G. H. et al. (1970) Report by HRC dated 22 October 1970 submitted to Novo Laboratories
See Also: Toxicological Abbreviations