CAFEINE CAS : 58-08-2 - UNEP Chemicals

OECD SIDS CAFFEINE
in the plasma was 30 µg/ml. Isolated lymphocytes from untreated donors administered this concentration
(30 µg/ml) several times were also negative. However, caffeine produced damage in human lymphocytes in
culture after a single 48h treatment with 250-750 µg/ml (Weinstein et al. 1972).
Further cytogenetic tests with bone marrow cells from mice and rats gave no indication of a clastogenic
effect (see IUCLID).
Most of the in vivo SCE-assays with rats, mice and hamsters were positive. However, in the 117 week
feed study in rats (Granberg-Oehman et al., 1978) no SCE induction was observed. However, a
toxicological relevance is questionable due to the other negative in vivo studies.
Caffeine was negative in the mouse bone marrow micronucleus test (i.p. administration of up to ca. 97
mg/kg) (King et al., 1979). In further micronucleus tests, Swiss CD-1 mice (in- and outbred mice)
received 50, 75 or 100 mg/kg bw caffeine and Chinese hamsters received 75, 150 or 300 mg/kg bw by
gavage twice with a 24h interval, and with the second dose being given 6h prior to sacrifice, or alternativly
given once 30h prior to sacrifice. Only the highest dose (in the range of the LD50) caused an induction of
micronuclei in hamsters and mice (Aeschbacher et al., 1986). Other poorly documented micronucleus
tests with rats and mice have been published and were also negative.
A study was performed by i.p. application to compare the ability of caffeine to induce micronuclei (in
mice and Chinese hamster) versus chromosomal aberrations , and SCE (in Chinese hamster)
(Tsuchimoto and Matter, 1979). In the micronucleus test with mice the doses used were 100 and 250
mg/kg bw and they were administered via i.p. twice with an interval of 24h. In the studies with hamsters,
100 and 200 mg/kg bw were used. For the micronucleus screening and chromosomal aberration tests, the
test substance was given twice via i.p. with an interval of 24h, and was only given one time via i.p. for the
SCE test. Niether a clastogenic effect nor an increase in SCE was seen in any of the studies.
In a Dominant lethal test male mice were gavaged with caffeine at 90 mg/kg bw for 5 consecutive days
or received it via drinking water at levels of 112 mg/kg bw for 8 weeks. No mutagenic induction of
dominant lethals, preimplantation losses or depression of female fertility attributable to the test substance
was observed (Aeschbacher et al., 1978). All other dominant lethal studies were likewise negative.
Conclusion:
A large number of in vitro results are available and were summarized in a comprehensive review (IARC
No. 51): Salmonella and classic E. coli studies were mostly negative. Special E. coli strains and
Saccharomyces showed positive results. In terms of gene mutation in mammalian cell cultures and UDS
assays, the results were consistently negative. Only at high concentrations were some indications of
clastogenic activity in cell lines found.
In the majority of in vivo tests (MNT; CA, DL, HMA) negative results were obtained in terms of
mutagenicity and clastogenicity. On the whole, the conclusion is drawn that under exposure relevant
conditions there are no indications of genotoxicity of caffeine. This is also the overall assessment of the
IARC evaluation (see publication No. 51, 1991 for more details).
3.1.7 Carcinogenicity
In a 104 week drinking water study, the substance was administered to Sprague-Dawley rats (groups of
50 animals/sex) at concentrations of 200, 430, 930 and 2000 ppm (12, 26, 49, 102 mg/kg bw/d males
and 15, 37, 80, 170 mg/kg bw/d, females). There was a slightly increased mortality in males at 2000 ppm.
Decreased body weights were found in both sexes at 930 ppm (11%) and 2000 ppm (25%), associated
with reduced food and water consumption.
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