The absorption and metabolism in rats of small oral doses of dimethylnitrosamine. Implication for the possible hazard of dimethylnitrosamine in human food

Abstract

1. Groups of rats were given one dose of the carcinogen dimethylnitrosamine by gastric intubation. The dose was varied between 10mg/kg body wt. and 1 microgram/kg body wt. 2. The dose was rapidly absorbed. 3. The methylation of liver DNA resulting from the administration of this carcinogen was proportional to dose. This suggests that small doses are absorbed from the gut with no more loss than large doses. 4. As the dose was decreased there was a disproportionately greater decrease in the alkylation of kidney DNA, and when the dose was less than 40 microgram/kg body wt. the methylation of kidney DNA was no longer detectable. This possibly explains why small amounts of dimethylnitrosamine in the diet do not induce kidney tumours. 5. Comparison of the relative alkylation of liver DNA and kidney DNA resulting from an oral and from an intravenous dose of dimethylnitrosamine suggest that small amounts of dimethylnitrosamine absorbed into the portal blood from the gut are completely metabolized by the liver and do not enter the general circulation. 6. The implications of these results for the possible hazard of dimethylnitrosamine in human food is discussed.

Predicting the oral uptake efficiency of chemicals in mammals: Combining the hydrophilic and lipophilic range

“…In the food studies, the contaminants were administered with or without fasting, diluted in oil or water, and dosed either with a stomach tube or mixed in the food (e.g. (Diaz-Gomez et al, 1977;Jones and Hathway, 1978). Most drugs and pollutants were administered as single doses, except in one food study which used multiple dosing.…”

Methylation of deoxyribonucleic acid in the rat by the mushroom poison gyromitrin

“…Hereby, it must be assumed that the dose-binding relationship is linear down to environmental doses of methylating agent. Good data are available to show that it is indeed the case for the generation of 7-methylguanine from doses of DMNA as little as 10 Mg/kg (Diaz Gomez et al, 1977). The relatively low methylating potency of gyromitrin does not allow the detection of DNA methylations at such low dose levels.…”

Toxicokinetics ofN-nitrosodimethylamine in the Syrian golden hamster

“…If it is also assumed that in the hamster, as has been demonstrated for the rat (Diaz Gomez et al 1977;Pegg and Perry 1981), all of an i.g. dose of NDMA is absorbed and reaches the liver in an unchanged form, then an alternative estimation of the metabolic capacity of the hamster liver can be made.…”