The Contribution of cocoa additive to cigarette smoking addiction

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Page 78 of 207 RIVM report 650270002 Histamine were administered to twelve patients (8 with metastatic melanoma and 4 with metastatic renal cell carcinoma). Histamine was administered slowly by subcutaneous injection over 20 minutes. Serial blood samples were collected during the first 240 min for analysis of serum histamine. The patient population was predominantly Caucasian (92%) and male (83%) with an average age of 52.3 years. Histamine had t1/2 12.7 min and Vd 66.0 l (39) (the histamine dose was not mentioned in the abstract). Critical assessment 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. All mammalian tissues that contain histamine are able to synthesise it from histidine by means of their contents of L-histidine decarboxylase. Histamine kinetic parameters determined in patients with melanoma’s had t1/2 12.7 min and Vd 66.0 l. The small t1/2, seems to implicate a rapid histamine metabolisation. Conclusion Histamine is absorbed through the respiratory system. However, due to the rapid histamine metabolisation it is not expected that the histamine dose in cigarette will be high enough to affect the plasma histamine level. TOXICOLOGY Acute toxicity Human Injection of histamine can produce a wide range of adverse effects that includes headache, flushing of the skin, general vasodilatation with a fall in blood pressure, tachycardia, bronchial constriction and dyspnoea, visual disturbances, vomiting, diarrhoea, and other gastrointestinal effects. These reactions may be serious and excessive dosage can produce collapse and shock, and may be fatal. Reactions may occur at the injection site (14). In a study a case of occupational histamine poisoning by spoiled fish flour via inhalation, skin and eye contact was described. Twenty harbour workers handled shipments of fish flour transported in black or blue bags. Ten workers handling blue bags developed allergy-like skin, eye, gastrointestinal, respiratory and cardiac symptoms within 30 min. Workers handling black bags were symptom-free, except for minimal eye irritation. The histamine content was 10-fold higher in samples from the blue than from the black bags (510 mg/100 g flour compared with 50 mg/100 g flour, respectively) (40). It is often stated that ingestion of foods rich in histamine can result in absorption of sufficient histamine to provoke signs and symptoms reminiscent of an allergic reaction. Histamine ingestion in excess of 36 to 250 mg may result in a clinical response, which includes abdominal complaints, feelings of warmth, flushing and headache. (41). Several foods contain histamine at levels potentially toxic for man; amongst the most frequently incriminated products is fish, especially the scombroid species (tuna, mackerel), which plays a pre-eminent role in the etiology of the so called scombrotoxic fish poisoning. This syndrome begins from a few minutes to two hours
RIVM report 650270002 Page 79 of 207 Histamine from incriminated meals and presents itself with the characteristic signs and symptoms of histamine activity on various organs and is very rarely, if ever, life threatening. Histamine formation in food is due to the decarboxylase activity of some microorganisms, mainly enterobacteria; they can be part of its normal flora or represent a secondary contamination and find a favourable environment for outgrowth if food is not stored or processed in proper conditions (42). Animal No data available Local tolerance Human Eye effect of an 8% (w/w) solution of histamine hydrochloride have been described in case of girl who spilled some on her handkerchief and contaminated her right eye. In 10 min conjunctivae became hyperaemic and lids oedematous, without discomfort. Reaction had nearly disappeared in 5 hr and completely gone next day. In some human glaucomatous eyes, application of 3% (w/w) histamine hydrochloride eyedrops has been known to cause rise in ocular pressure, particular in cases of acute glaucoma. Injected intradermally a triple response follows: red spot, flare developing and more slowly a localised oedema. These effects are due to local dilatation of minute blood vessels, the dilatation of neighbouring arterioles and the direct action on walls of vessels to increase their permeability (2). Animal scu-rat LDLo: 250 mg/kg (43) ivn-rat LD50: 630 mg/kg (43) orl-mouse LD50: 220 mg/kg (43) ipr-mouse LD50: 725 mg/kg (43) scu-mouse LD50: 2500 mg/kg (43) ivn-mouse LD50: 385 mg/kg (43) scu-dog LDLo: 28.5 mg/kg (43) ivn-dog LD50: 7 mg/kg (43) ivn-monkey LDLo: 50 mg/kg (43) scu-cat LDLo: 34 mg/kg (43) scu-rabbit LDLo: 12 mg/kg (43) ivn-rabbit LDLo: 2 mg/kg (43) orl-guinea pig LDLo: 200 mg/kg (43) ipr- guinea pig LD50: 5 mg/kg (43) scu- guinea pig LDLo: 8 mg/kg (43) ivn- guinea pig LD50: 0.18 mg/kg (43) scu- guinea pig LDLo: 1700 mg/kg (43) Repeated dose toxicity Subacute No data available. Semichronic No data available. Chronic
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The Contribution of cocoa additive to cigarette smoking addiction

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