The Contribution of cocoa additive to cigarette smoking addiction

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Page 80 of 207 RIVM report 650270002 Histamine 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 pathological and immunological histamine hyperresponsiveness (44). Pathological histamine levels are correlated with several disorders. Normal and pathological plasma histamine levels vary considerably in the literature. The normal range for human plasma histamine as 0-1.0 ng/ml. Values greater than 1 ng/ml have to be considered as pathological (45). Patients with B cell chronic lymphocytic leukemia (B-CLL) have decreased capacity to mount relevant antibody responses upon immunization, and development of hypogammaglobulinemia is part of the natural history of the disease. Plasma histamine levels determined in B-CLL patients were 2-fold to 20-fold higher in 23 out of 31 B-CLL patients, compared to normal controls and these levels showed a significant positive correlation to disease duration. The increased plasma histamine levels, strongly suggests the involvement of histamine in the pathogenesis of B-CLL immunodeficiency (46). In one study the basal plasma histamine level and eosinophil count in the peripheral blood in patients with a history of allergy (allergic patients) were examined and compared with those in patients without any history of allergy (non-allergic patients). The mean basal plasma histamine level in non-allergic patients (n = 70) and allergic patients (n = 70) were 0.31 ± 0.27 ng/ml and 0.47 ± 0.30 ng/ml, respectively (p < 0.01). The mean eosinophil counts in non-allergic patients and allergic patients were 3.3 ± 3.0% and 5.3 ± 3.4% of total white blood cells, respectively (p < 0.01). The patients who had asthma, atopic dermatitis or a food-induced allergy showed a high level of basal plasma histamine compared to that in non-allergic patients. The patients with asthma, allergic rhinitis or atopic dermatitis all demonstrated a higher eosinophil count than non-allergic patients. In addition, the correlation between the plasma histamine level and the eosinophil count was statistically significant (p < 0.05). It was concluded that the allergic patients had both higher basal plasma histamine levels and eosinophil counts than non-allergic patients (p < 0.01) (47). There was also a positive correlation between basal plasma and total blood-histamine levels (r = 0.67, p less than 0.01) in normal and asthmatic subjects suggesting that basophils contribute significantly to plasma histamine. The spontaneous basophil release of histamine was greater in asthmatic (13.4 ± 2%) than in normal subjects (6.46 ± 7%, p less than 0.005), which is consistent with the higher resting plasmahistamine levels in the asthmatic subjects (48). Carcinogenicity Human Endogenous histamine has been shown to affect growth mechanisms in experimental mammary carcinomas via cellmembrane containing H2 receptors. Both H1 and H2 binding sites are present in human mammary glands. About 75% of malignant carcinomas express H2 receptors. The presence of mast cells around tumour tissue raises questions concerning the source of histamine in breast tumour tissue (49). Animal
RIVM report 650270002 Page 81 of 207 Histamine No data available. Reproduction toxicology Human No data available. Animal No data available. Mutagenicity Human No data available. Animal Ames tests have been performed with imidazole and its principal metabolites, hydantoin and hydantoic acid, N-acetyl-imidazole and histamine. Imidazole and histamine were also tested in the unscheduled DNA synthesis (UDS) assay in primary rat hepatocytes. Imidazole gave consistently negative results in the Ames test, the UDS assay and the transformation assay. The three metabolites of imidazole, namely hydantoin, hydantoic acid and N-acetyl-imidazole, all gave negative results in the Ames test. Histamine gave no evidence of mutagenic activity in the Ames test or of genotoxicity in the UDS assay. These results indicate that imidazole and its metabolites are unlikely to present a mutagenic or carcinogenic hazard (50). Other Critical assessment 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. Epidemiologic 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 symptoms within 30 min. The histamine dose in cigarette smoking does not seem to be high enough to exert toxicological effects. Conclusion The histamine dose of cigarette smoking does not seem to be high enough to exert toxicological effects. However, the long-term effects of this compound via the respiratory system are not known and need to be studied. INTERACTIONS Chemical No data available. In vivo Maternal ethanol consumption during pregnancy results in an increase in the cerebral histamine levels of the fetus. An increase in the brain histamine levels is also observed in the newborn rats suckling on the ethanol-fed mothers compared to the corresponding controls. Acute administration of ethanol or acetaldehyde resulted in
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The Contribution of cocoa additive to cigarette smoking addiction

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