CAFEINE CAS : 58-08-2 - UNEP Chemicals

OECD SIDS CAFFEINE
5.9 Developmental Toxicity/
Teratogenicity
Further
Data
Corrosiveness/Irritation Skin
Corrosiveness/Irritation Eye
Rat
Rat
Rat
Rabbit
Rabbit
Drinking water day 0-20
Gavage, day 1-20, NTP
program
Gavage, day 1-20,allowed
to deliver, NTP
programm
OECD 404
OECD 405
Sensitisation Guinea Pig No data
Carcinogenicity Rat
5.11 Experience with Human
Exposure
Drinking water up to
2000 ppm, 104 weeks
Kinetic, Metabolism
Toxicity
Epidemiology
Cardiovascular
NOAEL maternal = 51 mg/kg bw/d
NOAEL fetotoxicity = 10mg/kg bw/d
NOAEL teratogen > 205 mg/kg bw/d
LOAEL maternal 40 mg/kg bw/d
NOAEL fetotoxicity = 40 mg/kg bw/d
NOAEL teratogen = 80 mg/kg bw/d
LOAEL maternal: 10 mg/kg bw/d
NOAEL fetotoxicty: 40 mg/kg bw/d
NOAEL teratogen: 40 mg/kg bw/d
Not irritating
Not irritating
Negative
Rapid absorption from gastrointestinal tract;
peak plasma levels reached after 15 to 120
minutes. Elimination half-life 2.5 to 4.5 h.
Metabolized by hepatic microsomal enzymes
(demethylation, 95 %). In both humans and
rats, excretion mainly occurs via urine (about
90 % dose in rats; > 95 % in humans).
Caffeine metabolism is qualitatively similar in
animals and humans. The main metabolic
pathways are: demethylation and
hydroxylation of the 8-position leading to the
formation of the respective uracil and uric acid
derivatives. There are, however, some
quantitative differences in the metabolic
profile.
Low doses (up to 2 µg/ml in blood): stimulation
of the central nervous system; high
blood concentrations (10-30 µg/ml): restlessness,
excitement, tremor, tinnitus, headache,
and insomnia. Alterations in mood and
sleep patterns, increase diuresis and gastric
secretions. Lethal dose: 5 g (overdosing).
Caffeine and coffee consumption are highly
correlated in most populations studied; thus it
is difficult to separate the two exposures in
epidemiologic investigations.
Bias or confounding has to be taken into
account in many of the studies.
No association between moderate consumption
of coffee/caffeine and cardiovascular diseases.
Caffeine consumed in moderate amounts did
not cause persistent increase in blood pressure
in normotensive subjects. Short-term clinical
studies have shown that in caffeine-naive
subjects, 250 mg of caffeine increased systolic
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