The Contribution of cocoa additive to cigarette smoking addiction

More documents

Recommendations

Info

Page 70 of 207 RIVM report 650270002 Histamine smoke. CONSENSUS REPORTS No data available. STANDARDS AND RECOMMENDATIONS ADI: An intake of > 40 mg biogenic amines (histamine, tryptamine, tyramine, phenylethylamine, etc.) per meal has been considered potentially toxic. Switzerland considered 10 mg histamine per liter wine a permissible limit. The European Economic Community has put a maximum limit for histamine in for fresh fish (200 mg/kg) and for enzymatically ripened fish (400 mg/kg) belonging to Scombridae and Clupedae families (8). 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: Skin histamine concentrations (2.09 ± 0.31 µg/l) were found to be significantly higher than plasma histamine concentrations (0.48 ± 0.08 µg/l) (9). Median plasma histamine concentration was reported to be 0.53 (range 0.21-1.59) µg/l (n = 18). Median total cell-bound histamine content was 46.3 (range 19.6 – 101.1) µg/l in whole blood and 52.8 (range 40.0 – 173.4) µg/l in plasma-reduced whole blood (10). The mean histamine content ranged from 2.5 ± 0.5 pg/mast cell for the smallest diameter mast cells (8-10 µm) to 10 ± 2.5 pg/mast cell for the largest (16-20 µm) (11). It was shown that plasma histamine levels followed biorhythmic changes with 3 maxima and 3 minima. The acrophases of the maxima are 12.77 ± 0.61, 19.33 ± 0.78 and 5.42 ± 1.83 h. The most important rise in plasma histamine levels was found in the early hours of the morning (12). CLASS EG Carc. Cat.: No data available. IARC-category: No data available. CEC: No data available. Critical assessment Comparison of smoking related potential daily intake of histamine with histamine daily intake from other sources SMOKING HISTAMINE INTAKE BY EATING OR DRINKING 25 cigarettes 3 chocolate wine Dutch cheese (1 % cocoa) bars of 60 g (125 g) (50 g) Histamine (µg) 0.33 (6) 200 (6) 185 (7) 2600 (7) .
RIVM report 650270002 Page 71 of 207 Histamine Little is known about the profile of the pyrolysis/combustion products of histamine. Conclusion The daily intake of histamine from cigarettes (from added cocoa) is about 500 times less than histamine intake from other sources such as chocolate, wine or Dutch cheese. Assuming similar bioavailability, the plasma concentration reached after ingestion of histamine from chocolate sources or other food sources is expected to be significantly higher, than after exposure from cigarettes. 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. PHARMACODYNAMICS Mechanism of action Histamine is an autacoid that is closely associated with mast cells and functions as a mediator of inflammation. Like serotonin, it is also a neurotransmitter in the central and peripheral nervous systems. Its effects are mediated by three receptor subtypes with differential selectivities for both agonists and antagonists (H1, H2 and H3) (13, 14) They share structural and membrane topography features with other metabotropic receptors. Histamine receptors H1 and H2 are postsynaptic whereas H3 is presynaptic. There are no known natural toxins or toxicants of histamine receptors. The H1 and H2 antagonists are potent therapeutics. The potent therapeutic H1 agonists are effective for the treatment of allergies, but their side effects and toxicities include sedation and anticholinergic actions. Antagonists for H2 receptor are excellent therapeutics for peptic and gastric ulcers, because of their ability to block histamine-induced gastric acid production (15). Recently a new histamine receptor, H4, was discovered in bone marrow and it may be a therapeutic target for the regulation of immune function, particularly with respect to allergy and asthma (16). H1-receptors have been detected in a wide variety of tissues including: mammalian brain, smooth muscle from airways, gastrointestinal tract, genito-urinary system, cardiovascular system, adrenal medulla, endothelial cells and lymphocytes. The primary mechanism by which histamine H1-receptors produce functional responses in cells is the activation of phospholipase C. An H1-receptor mediated increase in either inositol phosphate accumulation or intracellular calcium mobilization has been described. Histamine H2-receptors have a potent effect on gastric acid secretion. This receptor occurs in cardiac tissues, smooth muscle of the airway, uterine and vascular system in high densities and is widely distributed in the brain. H2-receptors in basophils and mast cells have been shown to negatively regulate the release of histamine. Histamine H2-receptors is coupled to the adenylyl cyclase via the GTP-binding protein Gs. H2receptor mediated effects on cAMP accumulation have been observed in brain cells, gastric mucosa, cardiac myocytes, vascular smooth muscle and neutrophils. Histamine H3-receptors have inhibitory effects on the neurotransmitter release in the CNS and in the periphery. The signal transduction pathway of the H3-receptor is
Page 1 and 2:
RIVM report 650270002/2002 The cont
Page 3 and 4:
RIVM report 650270002 Page 3 of 207
Page 5 and 6:
Page 7 and 8:
Page 9 and 10:
Page 11 and 12:
Page 13 and 14:
Page 15 and 16:
Page 17 and 18:
Page 19 and 20: RIVM report 650270002 Page 19 of 20
Page 47 and 48: Page 47 of 207 RIVM report 65027000
Page 69: RIVM report 650270002 Page 69 of 20
Page 121 and 122:
Page 123 and 124:
Page 125 and 126:
Page 125 of 207 RIVM report 6502700
Page 127 and 128:
Page 129 and 130:
Page 131 and 132:
Page 133 and 134:
Page 135 and 136:
Page 137 and 138:
Page 139 and 140:
Page 141 and 142:
Page 143 and 144:
Page 145 and 146:
Page 147 and 148:
Page 149 and 150:
Page 151 and 152:
Page 153 and 154:
Page 155 and 156:
Page 157 and 158:
Page 159 and 160:
Page 161 and 162:
Page 163 and 164:
Page 165 and 166:
Page 167 and 168:
Page 169 and 170:
Page 171 and 172:
Page 173 and 174:
Page 175 and 176:
Page 177 and 178:
Page 179 and 180:
Page 181 and 182:
Page 183 and 184:
Page 185 and 186:
Page 187 and 188:
Page 189 and 190:
Page 191 and 192:
Page 193 and 194:
Page 195 and 196:
Page 197 and 198:
Page 199 and 200:
Page 201 and 202:
Page 203 and 204:
Page 205 and 206:
Page 207:
show all

The Contribution of cocoa additive to cigarette smoking addiction

You also want an ePaper? Increase the reach of your titles

Delete template?

Save as template?