N-nitrosodiethanolamine: analysis, formation in tobacco products and carcinogenicity in Syrian golden hamsters.

An analytical GC-TEA method has been developed for the quantitative determination of N-nitrosodiethanolamine (NDELA) in tobacco and tobacco smoke. US smoking and chewing tobaccos and experimental cigarette tobaccos contained between 80 and 420 micrograms/kg of NDELA. Two snuff samples contained 3200 and 6800 micrograms/kg of NDELA. NDELA in mainstream smoke of US cigarettes amounted to 10 - 68 ng per cigarette. Evidence was presented which incriminates diethanolamine as a major precursor for NDELA in tobacco and tobacco smoke. Diethanolamine is used as a solubilizing agent for maleic hydrazide, the major sucker-growth inhibitor for US tobacco crops. NDELA was bioassayed in Syrian golden hamsters by skin painting, swabbing of the oral cavity and by subcutaneous injection. Independently of the form of application, NDELA at the higher dose (500 mg/kg) induced carcinomas of the nasal cavity, papillomas of the trachea and tumours of the larynx in some animals. NDELA uptake through the oral cavity in hamsters is presumably greater than through the skin, judging by the higher tumour yield induced by painting of the oral cavity, compared to skin painting. Studies with 14C-labeled NDELA are currently underway to document this observation quantitiatively. The present analytical data for NDELA in tobacco and tobacco smoke, together with the carcinogenicity data reported here and elsewhere, strongly suggest a review of the use of maleic hydrazide-diethanolamine as sucker-growth inhibitor in the cultivation of tobacco and other crops.