FAST GREEN FCF EXPLANATION Fast Green FCF was evaluated at the twenty-fifth and twenty-ninth meetings of the Committee (Annex 1, references 56 and 70) when toxicological monographs were prepared (Annex 1, references 57 and 71). A temporary ADI of 0-12.5 mg/kg b.w. was allocated at the twenty-fifth meeting. At the twenty-ninth meeting it was noted that a mouse oral carcinogenicity study was negative but that, in the rat study, an increased incidence of urothelial hyperplasia and/or neoplasia of the bladder was observed at the highest dose level. The biological significance of observed differences in benign and malignant tumours at other sites was considered questionable since, apart from the bladder, complete histological examination was not performed on the low- and intermediate-dose groups. The temporary ADI was extended to 1986 to permit complete histological examination of all groups of rats and biometric examination of the data. Since the previous evaluation, these new data have become available and are summarized in the following monograph addendum. BIOLOGICAL DATA Toxicological studies Special study on carcinogenicity A review of the histopathological data from the rat oral carcinogenicity study (Knezevich & Hogan, 1981) was performed from which it was concluded that inappropriate statistical tests had been performed on some of the data by the testing laboratory. Using appropriate statistical procedures the reviewers concluded that there were no significant differences in tumour incidence between combined control groups and the high-dose group with respect to tumours of the liver, testes, or thyroid; the tissues from the low- and intermediate-dose groups were not examined. In a blind review of the slides of the bladders from all dose groups, only three proliferative lesions, two benign (papilloma) and one malignant (carcinoma), were observed in bladders of male rats in the high-dose group and a treatment-related increase in the incidence or severity of transitional cell hyperplasia was not detected. It was concluded that the observation of only three neoplasms in the high-dose male group, two of which were of questionable neoplastic character, and the absence of evidence of a pre-neoplastic process in the observed hyperplasia, established that there is no indication of a neoplastic effect on the urinary bladder from administration of Fast Green FCF (Dua et al., 1982, O'Donnell, 1982, US FDA, 1952 a,b). Comments Biochemical studies have shown that the colour is poorly absorbed and no adverse effects were observed in a 3-generation reproduction/teratogenicity study. The earlier mouse carcinogenicity study was negative and a review of the rat carcinogenicity study indicates that Fast Green FCF is also non-carcinogenic in this species. EVALUATION Level causing no toxicological effect Mouse: 5% in the diet, equal to 18,600 mg/kg b.w./day falling to 8000 mg/kg b.w./day. Rat: 5% in the diet, equivalent to 2,500 mg/kg b.w./day. Estimate of acceptable daily intake for man 0 - 25 mg/kg b.w. REFERENCES Dua, P.N., Chowdury, K.A., & Moch, R.W. (1982). Pathology report on FD&C Green No. 3. Unpublished pathology report, Project No. PR-75, CAP No. 8C0065. Submitted to WHO by the US FDA. Knezevich, A.L. & Hogan, G.K. (1981). A long-term oral toxicity/ carcinogenicity study of FD&C Green No. 3 in rats. Unpublished report No. 77-1780 from Bio/dynamics Inc., East Millstone, NJ, USA. Submitted to WHO by Certified Color Manufacturers' Association. O'Donnell, M.W. (1982). Memorandum, Long-term oral toxicity/ carcinogenicity studies of FD&C Green No. 3 in rats. Unpublished report, Project No. 77-1780. Submitted to WHO by the US FDA. US FDA (1982a). Memorandum of conferences Feb. 4 and Aug. 30, 1982 of the Cancer Assessment Committee. Submitted to WHO by the US FDA. US FDA (1982b). Federal Register, 47, 52140-52145.
See Also: Toxicological Abbreviations Fast green FCF (FAO Nutrition Meetings Report Series 46a) Fast Green FCF (WHO Food Additives Series 16) Fast Green FCF (WHO Food Additives Series 20) FAST GREEN FCF (JECFA Evaluation) Fast Green FCF (IARC Summary & Evaluation, Volume 16, 1978)