The Contribution of cocoa additive to cigarette smoking addiction

RIVM report 650270002 Page 85 of 207
Histamine
or other food sources is expected to be significantly more, than after exposure to
cigarette smoking. However, the different route of application via smoking as
compared to other sources should be taken into account. Therefore, the systemic and
the local effect of smoking related exposure to histamine might be a point of concern.
Since nothing is known about the pyrolysis/combustion products of histamine in
cigarette smoke, this may be an additional point of concern.
Histamine is an autacoid that is closely associated with mast cells and functions as a
mediator of inflammation. Histamine is a neurotransmitter in the central and
peripheral nervous systems. It mediates its effects through three receptor subtypes
with differential selectivities for both agonists and antagonists (e.g., mepyramine for
H1, ranitidine for H2, and thiperamide for H3). Through these receptors, histamine
evokes several physiological effects. Histamine characteristically causes dilatation of
the finer blood vessels, resulting in flushing, lowered total peripheral resistance and a
fall in systemic blood pressure. The released cardiac histamine is a major mediator of
arrhythmias that occur during anaphylaxis and following the administration of
histamine-releasing drugs. Histamine receptors are widely distributed in the CNS.
The central histamine receptors may regulate the cardiovascular system, diuresis and
food intake. Histamine also induces gastric secretion. Histamine provokes
bronchoconstriction, but some conflicting results were found concerning the
breathing frequency and the tidal volume. It seems that different mechanisms with
opposite effects are acting simultaneously.
The histamine dose causing a 20% fall in forced expiratory volume in one second
(PD20) was shown to be between 0.73 mg -1.20 mg in young normal adults. In
astmatics the histamine dose for PD20 was 0.23 mg. The estimated daily histamine
intake through cigarette smoking is about 2000 times less than the PD20 in normal
adults.
14 C and 3 H-histamine studies showed that histamine is absorbed through the
pulmonary system. Almost all mammalian tissues contain histamine in amounts
ranging from less than 1µg up to more than 100 µg/g tissue. Every mammalian tissue
that contains histamine is able to synthesise it from histidine by virtue of its contents
of L-histidine decarboxylase. There are two major pathways of histamine metabolism
in man. The more important of these involves methylation and is catalysed by the
enzym histamine-N-methyltransferase, which is widely distributed. Most of the
product, N-methylhistamine, is converted by monoamine oxidase (MAO) to Nmethyl
imidazole acetic acid. The metabolites resulting from catalysation are
excreted in the urine. Histamine kinetic parameters determined in patients with
melanoma’s had t1/2 12.7 min and Vd of 66.0 l. The small t1/2 seems to implicate a
rapid histamine metabolisation.
Hyperresponsiveness to histamine is a key feature of a variety of pathological
conditions, including bronchial asthma, food allergy, colitis ulcerosa, and topical
allergic disorders. Several mediators enhance the cellular reaction to histamine in cell
types involved in patho-immunological histamine hyperresponsiveness.
Epidemiological reports on food-borne diseases from different countries show
frequent outbreaks due to histamine toxicity. Workers exposed to high histamine
dose developed allergy-like skin, eye, gastrointestinal, respiratory and cardiac