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.


    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).


         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.


    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.


    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'

    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)