The Contribution of cocoa additive to cigarette smoking addiction

Page 34 of 207 RIVM report 650270002
Caffeine
combination with known carcinogens resulted in decreased incidences of lung
tumours in mice treated with urethane, of mammary tumours in rats treated with
diethylstilboestrol and of skin tumours in mice treated with either ultraviolet light or
cigarette-smoke condensate (1).
Reproduction toxicology
Human
Total caffeine intake, as determined from various sources including coffee, tea, cola
and drugs, was positively associated with the proportion of low-birthweight babies
after controlling for smoking and other potential confounders (1).
For spontaneous abortion, five studies were evaluated; the combined odds ratio was
1.36 (95% confidence interval 1.29-1.45), indicating that mothers who consumed
caffeine had a higher risk of spontaneous abortion than those who did not. The birth
weight of the babies showed a statistical correlation with the caffeine consumption
during pregnancy (28).
In human some conflicting results were reported about the effects of caffeine and
coffee consumption on fertility. Some studies did not show any correlation between
caffeine intake and fertility and other studies showed a threshold and negative doseresponse
correlation between caffeine intake and fertility (29).
Animal
Caffeine in a dose of 25 mg/kg body weight administered by oral gavage to pregnant
rats on days 8-9 of gestation caused delayed neuraltube closure in rat embryos; also
the development of the heart, eyes and limbs were reduced.
From the various recent studies on the reproductive toxicity of caffeine, it is evident
that administration of caffeine during pregnancy affects the normal differentiation of
foetal ovaries and testis resulting in significant foetal and post natal growth
retardation and an increase in post natal mortality and impaired brain differentiation
resulting in delayed closure of the neural tube (8).
Mutagenicity
Human
Cultured human lymphocytes from volunteers on a regime of 800 mg caffeine daily
for four weeks, resulting in caffeine blood levels as high as 29.6 µg/ml after four
weeks showed no significant increase in the frequency of chromosomal damage.
Drinking coffee or tea to result in a total caffeine intake corresponding to that in five
cups of coffee per day [exact amount not stated] was associated with increased
micronucleated reticulocytes and micronucleated mature erythrocytes in
splenectomized but otherwise healthy individuals after adjustment for smoking.
Drinking decaffeinated coffee was not associated with an increase in the number of
micronucleated cells.
Although it has been suggested that caffeine may induce gene mutations in mammals
and man, direct evidence in vivo is limited. The indirect evidence is based largely on
extrapolation from results in lower organisms, in which there is no doubt about the
mutagenic action of caffeine, and from cultured mammalian cells, in which caffeine
is clastogenic at high concentrations (1).
Animal
Using dominant lethal method, no significant increase in dominant-lethal mutations
(embryonic deaths) were found, whether expressed as early deaths per pregnant
female or as mutation index in animals consuming caffeine in drinking water at 3.6,
13.4, 49 and 122 mg/kg for 8 weeks. Although males consuming the two highest