CAFEINE CAS : 58-08-2 - UNEP Chemicals

OECD SIDS CAFFEINE
5. TOXICITY DATE: 04-MAR-2003
SUBSTANCE ID: 58-08-2
stimulated to proliferate by a partial cystectomy or
cyclophospamide. No cocarcinogenic and/or promoting activity
of the test substance on BBN-initiated bladder tumor
development was observed. In contrast, increased tumor
incidences were seen in rats given the test substance in
combination with phenacetin; this increase was greater than
an increase observed in rats given phenacetin alone.
Test substance: caffeine
Reliability: (3) invalid
only one dose tested, initiation/promotion test
17-DEC-2001 (271)
Species: mouse Sex: female
Strain: other: C3H, BD2F, BALB/c
Route of administration: drinking water
Exposure period: 43 weeks
Frequency of treatment: continuously in the drinking water
Post exposure period: no data
Doses: ca. 50, 100 mg/kg/d (250, 500 mg/l = 250, 500 ppm in
the drinking water)
Control Group: yes, concurrent no treatment
Method: other: no data
Year: 1988
GLP: no data
Test substance: other TS
Remark: Histopathology was limited to mammary gland.
initiation/promotion study
Result: The effect of the test substance on carcinomatous and normal
mammary gland development was studied in BD2F mice
(54-55/group), C3H mice (37-43/group), and BALB/c mice
(20/group).
BD2F mice were administered the test substance in the
drinking water starting 1 week after a series of 6 weekly
7,12-dimethylbenz(a)anthracene (DMBA) injection. C3H mice
were administered the test substance without any
pretreatment. In both strains, administration of the test
substance (low and high dose) resulted in an increse in
mammary carcinoma multiplicity (by 20 and 40%, respectively,
in BD2F mice and by 13 and 117%, respectively, in C3H mice).
In contrast, the incidence of mammary carcinomas (i.e. the
percentage of mice bearing mammary tumors) and mean time to
tumor appearance as well as body weight gain were not
affected. An increase of mammary adenocarcinomas per animal
was noted.
In a second series of studies, the effect of the test
substance on mammary gland development in BALB/c mice was
assessed in vivo (0, 500 mg/l in the drinking water) and in
vitro (organ culture). In treated mice, mammary gland
development was significantly increased. In the organ
cultures, mammary glands derived from treated mice were more
responsive in vitro to a mammotropic hormonal developmental
growth stimulus than were mammae derived from untreated
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