The Contribution of cocoa additive to cigarette smoking addiction

Page 134 of 207 RIVM report 650270002
Tyramine
mg/kg) 24 h after intraperitoneal administration. Micronuclei were significantly
induced but no severe reduction in the ratio of polychromatic/normochromatic
erythrocyte was observed (38).
The acute cytogenetic effects of tyramine, precursor of tyramine derived mutagen
present in soy sauce, was studied with the in vivo chromosome aberration test in rat
bone marrow cells. Tyramine was administered intraperitoneally. Statistically
significant positive result was obtained with tyramine at a dose of 5 mmole/kg (686
mg/kg) body weight. Chromosome aberrations (CA) induced by L-proline coadministered
with tyramine were significantly lower than those induced by tyramine
alone. These data suggest that L-proline, after endogenous nitrosation, became
nitrosoproline and suppressed CA, and that, as a result of in vivo nitrosation of
tyramine, they became mutagenic nitroso compounds showing positive results.
Statistically significant positive results were obtained by administration of 40 mmole
NaCl/kg body weight (2338 mg/kg). The cocarcinogenic role of NaCl with tyramine
was suggested because soy sauce contains about 18% NaCl (39).
Mutagenicity of nitrite treated Japanese soy sauce (4 kinds) and tyramine, which is a
precursor of a mutagen (3-diazotyramine) and present in soy sauce, was studied in
Chinese hamster V79. Nitrite-treated tyramine was mutagenic for the cells; it induced
8.6, 13.3, and 18.3 TG-resistant mutants per 10 -5 clonable cells at concentrations of
20 µM, 56 µM, and 112 µM, respectively (40).
Other
Critical assessment
Small amounts of pressor amines, which are normally considered to be harmless, in
foods can lead to a hypertensive crisis in patients on monoamine oxidase inhibitor
(MAOI) drug regimens. Consumption of 6 mg of tyramine may produce a mild crisis
whereas 10 to 25 mg may produce severe headaches with intracranial hemorrhage.
The oral NOAEL in rat was 180 mg/kg body weight/day. The tyramine dose in one
cigarette (0.4 mg/cigarette) seems to be too low to have a significant systemic
toxicological effect. However, no data are available on the inhalation toxicological
effect of tyramine. Tyramine forms diazo-derivatives with nitrite, which are
carcinogenic and mutagenic.
Conclusion
data are available on inhalation toxicological effects of tyramine and its combustion
products. The long-term effect of this compound via the respiratory system needs to
be studied.
INTERACTIONS
Chemical
A reaction of p-tyramine and other biogenic amines 5-hydroxytryptamine, dopamine,
histamine, beta-phenylethylamine and tryptamine with components of cigarette
smoke was observed. Both formaldehyde and cyanide, which are known to be present
in cigarette smoke, were involved in the reaction with the primary amines. The
reaction was time dependent and was enhanced by an increase in temperature or by
incubation under alkaline conditions. Cyanomethyl adduct formation was increased