Nitrosation of bromhexine and aminophenazone in gastric juice after high nitrate loading in the diet. An ex-vivo/in-vitro study in humans.
In an ex-vivo study, nitrosation of bromhexine (N-methyl-N-cyclohexyl-(2-amino-3,5-dibromobenzyl)-ammonium hydrochloride) in human gastric fluid under conditions of high dietary nitrate intake was investigated. 26 healthy volunteers received 200 mg of nitrate in a vegetable during a standard breakfast. Nitrite values in saliva were significantly increased 2 to 3 h after nitrate intake. In contrast, nitrite levels in gastric fluid sampled 3 h after nitrate intake remained in the low concentration range of less than or equal to 1.7 micrograms/No2-/ml. Incubation of gastric fluid samples at 37 degrees C with the recommended maximum single oral dose of bromhexine (16 mg/100 ml) or an equimolar concentration of aminophenazone revealed in 4/26 cases formation of N-nitrosomethylcyclohexylamine from bromhexine at barely detectable levels. In contrast, aminophenazone generated N-nitrosodimethylamine at a very high rate, resulting in yields of greater than 50% in several samples. In view of the average daily background exposure to preformed nitrosamines in foods (0.5-1 microgram/capita), according to these results the possible contribution of in-vivo nitrosation of bromhexine corresponds at best to 10% in addition to the daily background exposure and therefore can be regarded as negligible.
Schlemmer
K H
KH
Department of Food Chemistry and Environmental Toxicology, University of Kaiserslautern, Fed. Rep. of Germany.
Eisenbrand
G
G
D000632:Aminopyrine / Q000032:analysis / Q000378:metabolism*; D001964:Bromhexine / Q000032:analysis / Q000378:metabolism*; D015197:Carcinogenicity Tests; D002849:Chromatography, Gas; D004032:Diet; D004128:Dimethylnitrosamine / Q000096:biosynthesis; D005750:Gastric Juice / Q000032:analysis / Q000378:metabolism*; D006801:Humans; D006863:Hydrogen-Ion Concentration; D066298:In Vitro Techniques; D009566:Nitrates / Q000008:administration & dosage* / Q000378:metabolism; D009573:Nitrites / Q000032:analysis; D009602:Nitrosamines / Q000096:biosynthesis*; D012463:Saliva / Q000032:analysis
D009566:Nitrates; D009573:Nitrites; D009602:Nitrosamines; D000632:Aminopyrine; D004128:Dimethylnitrosamine; D001964:Bromhexine; C025137:N-nitroso-N-methylcyclohexylamine