The Contribution of cocoa additive to cigarette smoking addiction

RIVM report 650270002 Page 137 of 207
Tyramine
are available on the respiratory pharmacokinetics of tyramine in man, but the lung
MAO will metabolise inhaled tyramine. Tyramine taken orally is normally
detoxicated by monoamine oxidase, present in intestine and liver, to yield parahydroxyphenylethanol,
para-hydroxyphenylacetic acid and its glycine conjugate,
para-hydroxyphenaceturic acid, and n-acetyltyramine.
Small amounts 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 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. The oral NOAEL from a diet study in rat
was 180 mg/kg body weight/day. Tyramine forms diazo-derivatives with nitrite,
which are carcinogenic and mutagenic.
Tyramine contains two reactive sites of different nature: the aliphatic aminogroup
(base) and the phenolic hydroxylgroup (slightly acidic). Tyramine interacts with
monoamine oxidase inhibitors and anti-hypertension drugs. There are no data
available on dependency or smoking cessation.
Since no data are available on pharmacodynamic, pharmacokinetic and toxicological
effects of tyramine exposure through inhalation, the shortterm and longterm effects of
exposure to tyramine through smoking on the respiratory system cannot be
established. Furthermore, its additive effects on other biogenic amines present in
cigarette smoke are also not known and have to be studied.
More studies are needed on:
- the determination of pyrolysis/combustion products of tyramine in cigarette
smoke;
- the local (respiratory system) effects of long-term use of tyramine alone and its
pyrolysis/combustion products via inhalation;
- the local (respiratory system) effects of long-term use of tyramine in combination
with other biogenic amines via inhalation.
Date this sheet was generated
Based on literature available in january 2002.
REFERENCES
(1) Dictionary of substances and their effects (DOSE). The Royal Society of
Chemistry, editor. 10/2000 . 2001. Electronic version.
(2) Brandweerinformatiecentrum voor gevaarlijke stoffen (BIG). Electronic
version 9.0, 2001. Belgium.
(3) Handbook of Chemistry and Physics. 79th edition . 1999. CRC, Electronic
version by William Andrew Publishing, USA.