The Contribution of cocoa additive to cigarette smoking addiction

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Page 28 of 207 RIVM report 650270002 Caffeine COMBUSTION PRODUCTS By heating/combustion of caffeine, toxic and corrosive gas/vapour are formed, such as nitrous gasses, carbon monoxide, carbon dioxide. Caffeine reacts with (strong) oxidants (3). CONSENSUS REPORTS There is inadequate evidence for the carcinogenicity of caffeine in humans. There is inadequate evidence for the carcinogenicity of caffeine in experimental animals. Caffeine is not classifiable as to its carcinogenicity to humans (group 3) (1). STANDARDS AND RECOMMENDATIONS ADI: Most obstetricians recommend that caffeine intake be limited to less than 400 mg/day during pregnancy (9). No ADI data are available for normal caffeine consumption. TWANL = MAC: no data available TWAD =MAK: no data available TWAUSA: no data available STELNL: no data available STELUSA: no data available LTEL: no data available TLV-C: no data available TLV-CARCINOGENICITY: no data available MAK-REPRODUCTION: no data available Others: Reference value: The median plasma caffeine concentration of a population over a wide age, was 1.71 µg/ml (range 0.10-6.74 µg/l) (10). Although the caffeine intake was not increased during pregnancy by women, the mean caffeine plasma concentration increased from 2.35 µg/l at beginning to 4.12 µg/l at 36 weeks of pregnancy, due to decreased clearance of caffeine during pregnancy (11). CLASS EG Carc. Cat.: No data available IARC-category: group 3 (1). CEC: No data available
RIVM report 650270002 Page 29 of 207 Caffeine Critical assessment Comparison of smoking related daily consumption with daily consumption of caffeine (mg) from other sources: SMOKING DRINKING OR EATING 25 cig. 3 3 3 3 3 (1% cocoa) Coffee Tea Chocolate Chocolate Cocoa drinks drinks bars of 60 g drinks . Caffeine (mg) 0.5 186 (12) 95 (12) 12 (12) 40 (milk) (13) 15 (1) 240-405 (9) 36 (milk) (14) 12 (sweet) (15) . Little is known about the profile of the pyrolysis/combustion products of caffeine. Conclusion The daily intake of caffeine from cigarettes through inhalation is marginal compared with the oral intake of caffeine from other sources, like coffee, tea, chocolate drink and sweets. So, the plasma concentration reached after ingestion of caffeine from coffee, tea or chocolate sources is expected to be significantly higher, than after intake from cigarettes. However, the different route of application via smoking as compared to other sources should be taken into account. Therefore, local effects of caffeine on the respiratory system might be a point of concern. PHARMACODYNAMICS Mechanism of action It was initially thought that caffeine and other methylxanthines acted primarily as phosphosdiesterase inhibitors. However, the inhibition is minimal at typical serum levels. At present it appears that the most important mechanism of action of caffeine is the antagonism of adenosine receptors. Adenosine is a locally released purine hormone that acts on two different receptors, A1 and A2. Receptors mediate either an increase or a decrease in cellular concentrations of cyclic adenosine monophosphate. High affinity (A1) receptors inhibit adenylate cyclase; low affinity (A2) receptors stimulate adenylate cyclase. Adenosine receptors are found throughout the body, including the brain, the heart and bloodvessels, the respiratory tract, kidneys, adipose tissue and the gastrointestinal tract. Adenosine acts locally as a vasodilator. It also reduces platelet aggregretion in vitro, inhibits catecholamine and renin release and inhibits lipolysis. Caffeine nonselectively inhibits the action of adenosine (9). Pulmonary system breathing frequency: The respiratory rate correlates closely with the plasma caffeine level ( 250 mg oral intake) (9). The major respiratory effect of caffeine (ingested from coffee) is an increased output of the respiratory centre. In healthy subjects caffeine (650 mg ingestion) significantly increases ventilation at rest, accompanied by a fall in an end tidal carbon dioxide tension (16). tidal volume: Caffeine increased the tidal volume during exercise after ingestion of 3.3 mg/kg body weight (17) or after 650 mg ingestion (18). lung compliance: The expired ventilation volume increased significantly after caffeine ingestion (18, 19). airway resistance: Caffeine has a bronchodilatory effect in humans through oral .
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The Contribution of cocoa additive to cigarette smoking addiction

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