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.