The Contribution of cocoa additive to cigarette smoking addiction

RIVM report 650270002 Page 33 of 207
Caffeine
(males); 137, 249, 247, 224 (females) (2).
LD50 rat is 261 – 383 mg/kg (26).
Intraperitoneal
LDs50 rat is 200 mg/kg, guinea pig is 235 mg/kg (1).
I.V.
LD50 rat is 105 mg/kg, mouse is 100 mg/kg and dogs is 175 mg/kg (1).
Local tolerance
Human
No data available.
Animal
No data available.
Repeated dose toxicity
Subacute
No data available
Semichronic
The maximum dose for rats to produce no deaths in 100 days (100 mg/kg)
corresponds to a man drinking some 60-100 cups of coffee a day. However, oral
doses of 110 mg/kg for 100 days in rats exhibited a stressor reaction in the form of
hypertrophy of the adrenal cortex and atrophy of the adrenal cortex and the thymus
gland. Some animals manifested a psychotic-like mutilation, gastric ulcers,
hypertrophy of the salivary glands, liver, heart, kidneys and lungs, inhibition of
oogenesis, minor changes in organ water levels and an occasional death apparently
from bronchiopneumonia. Although major changes in growth rates, eating and
drinking habits were not apparent, some polydipsia and diuresis, thyroiditis,
occasional dermatitis, some degree of nephritis and loss of red pulp in the spleen were
seen (5).
Caffeine also induced thymic atrophy at a dietary level of 0.5 % (± 150 mg/kg BW)
when fed for eight weeks in rats (27).
Chronic
The available data indicate that consumption of caffeine in moderate amounts does
not cause a persistent increase in blood pressure in normotensive human subjects.
Some controversy results were obtained about correlation between fibrocystic breast
disease and the use of caffeine (1).
Carcinogenicity
Human
A cohort study and four case control studies of breast cancer showed no association
with caffeine intake. A slight increase in risk was seen in premenopausal women in
one study, but in general the relative risk was below unity. Another case control study
of bladder cancer showed a weak association with caffeine consumption. The
problem in these population studies is that caffeine intake is highly correlated with
coffee intake, which makes it difficult to evaluate the effect of caffeine adequately
(1).
Animal
Caffeine was tested for carcinogenicity in five studies in rats by oral administration,
with caffeine concentration as high as 2000 mg/l drinking water. From the data
evaluation of these studies it was concluded that tumour incidence was not increased
significant at any site in the body in the caffeine group. Administration of caffeine in