Rickard R W, Dorough H W
J Toxicol Environ Health. 1984;14(2-3):279-90. doi: 10.1080/15287398409530580.
The N-nitrosocarbamates are potent mutagens and carcinogens, and have been synthesized under acid conditions that prevail in the human stomach. However, it has never been documented that nitrosocarbamates are actually formed in vivo in the stomach of any mammalian species. Using 14C-labeled carbaryl and carbofuran, attempts were made to isolate the nitroso derivatives from the stomach contents of rats and guinea pigs treated orally with the carbamate and sodium nitrite. Only trace quantities of nitrocarbamate were recovered from the rat stomach, whereas 0.5 to 2.0% of the carbamate doses were isolated as the nitroso derivative from the contents of the guinea pig stomach. The rather low apparent yields resulted in part from the instability of the nitrosocarbamates and from absorption of the carbamate and/or nitrosocarbamate from the stomach. Higher rates of synthesis were indicated by incubating the carbamates with sodium nitrite in the presence of the stomach contents at 37 degrees C for 15 min. About 30% nitrosation occurred with the guinea pig and about 0.5% with the rat. The difference was attributed to the pH of the gastric contents. For the rat, the pH ranged from 3 to 5; gastric contents of the guinea pig had a pH between 1 and 2. Since the pH of the human stomach is also in the pH 1-2 range, it is likely that nitrosation of carbamates in humans would be very similar to that in the guinea pig.
N-亚硝基氨基甲酸酯是强效诱变剂和致癌物，在人类胃中普遍存在的酸性条件下已被合成。然而，从未有文献记载在任何哺乳动物物种的胃中实际形成过亚硝基氨基甲酸酯。使用14C标记的西维因和克百威，试图从经氨基甲酸酯和亚硝酸钠口服处理的大鼠和豚鼠的胃内容物中分离出亚硝基衍生物。从大鼠胃中仅回收了痕量的硝基氨基甲酸酯，而从豚鼠胃内容物中分离出0.5%至2.0%的氨基甲酸酯剂量作为亚硝基衍生物。相当低的表观产率部分是由于亚硝基氨基甲酸酯的不稳定性以及氨基甲酸酯和/或亚硝基氨基甲酸酯从胃中的吸收。通过在37℃下将氨基甲酸酯与亚硝酸钠在胃内容物存在下孵育15分钟，表明合成速率更高。豚鼠发生约30%的亚硝化，大鼠发生约0.5%的亚硝化。差异归因于胃内容物的pH值。对于大鼠，pH值范围为3至5；豚鼠的胃内容物pH值在1至2之间。由于人类胃的pH值也在1-2范围内，氨基甲酸酯在人类中的亚硝化可能与豚鼠非常相似。
