Quantitative measurement of the exhalation rate of volatile N-nitrosamines in inhalation experiments with anaesthetized Sprague-Dawley rats.
Volatile N-nitrosamines have been detected in the human environment--in work places, such as the rubber, leather and chemical industries, in tobacco smoke and also inside new cars. In order to make risk assessments on the basis of inhalation experiments with animals at dose levels relevant to the human situation, it is important to know the actual absorption rate in the respiratory tract. In this study, 63 female Sprague-Dawley rats were exposed to four nitrosamines (N-nitrosodimethylamine, N-nitrosodiethylamine, N-nitrosopyrrolidine and N-nitrosomorpholine) in air. Respiratory parameters were monitored by pneumotachography. After 10 min of inhalation, the exhaled air was collected for 10 min in steps of 2 min intervals and analysed for its content of nitrosamines with a Thermal Energy Analyzer. Inhalation and exhalation were maintained by endotracheal intubation under narcosis with Thalamonal. The influence of this anaesthetic on the urinary excretion of N-nitrosodimethylamine after gavage and inhalation was tested: in comparison with unanaesthetized animals and with a group under ether narcosis, the excretion of the nitrosamine by the Thalamonal-anaesthetized animals was drastically reduced (factor of 20 to 60). Independent of the concentration of inhaled nitrosamine, ranging from 1-450 micrograms/L in air, the relative amounts of exhaled substance 10 min after inhalation were 0.9% N-nitrosodimethylamine, 0.4% N-nitrosodiethylamine, 6% N-nitrosopyrrolidine and 5% N-nitrosomorpholine. Extrapolation of these data back to the first exhalation (i.e., following the last inhalation) revealed that a remarkable amount of substance may be exhaled (up to 30% N-nitrosodimethylamine).
D000393:Air Pollutants / Q000032:analysis; D000777:Anesthetics / Q000494:pharmacology; D000818:Animals; D001944:Breath Tests; D004329:Droperidol / Q000494:pharmacology; D004338:Drug Combinations / Q000494:pharmacology; D005260:Female; D005283:Fentanyl / Q000494:pharmacology; D009602:Nitrosamines / Q000032:analysis / Q000378:metabolism* / Q000652:urine; D051381:Rats; D011919:Rats, Inbred Strains
D000393:Air Pollutants; D000777:Anesthetics; D004338:Drug Combinations; D009602:Nitrosamines; C001451:Innovar; D004329:Droperidol; D005283:Fentanyl