Savolainen H, Rosenberg C
Arch Toxicol. 1983 Jun;53(2):143-50. doi: 10.1007/BF00302722.
Male Wistar rats exposed intermittently to 300 ppm (12.5 mumol/l) morpholine vapour 5 days a week for 6 h daily during 4-15 weeks displayed an increasing brain solvent content analyzed by a sensitive gas chromatographic method. Rats drinking water which contained 150 mg NaNO2/l during the vapour exposure period showed initially larger brain solvent concentrations which began to decrease after 8 weeks. Fat solvent concentrations were a fraction of those detected in brain of the solvent-exposed animals or of those in the combined exposure. Nitrite exposure alone caused decreased spinal cord axon acetylcholine esterase activity after 8 weeks while this effect was noted in the combined exposure only at 8 weeks disappearing later on. Axonal succinate dehydrogenase activity was below the controls in the combined exposure throughout the study, and combination also caused persistent increase in the muscle creatine kinase activity. The morpholine-induced effects were less remarkable. The results point at pharmacokinetic interaction between the solvent and nitrite with its own effects on energy metabolism. No N-nitrosomorpholine was found although other metabolic interactions could not be excluded.
雄性Wistar大鼠在4至15周期间,每周5天、每天6小时间歇性暴露于300 ppm(12.5 μmol/l)吗啉蒸气中,通过灵敏的气相色谱法分析显示其脑溶剂含量不断增加。在蒸气暴露期间饮用含150 mg NaNO₂/l水的大鼠,最初脑溶剂浓度较高,8周后开始下降。脂肪溶剂浓度仅为溶剂暴露动物脑内检测值或联合暴露组的几分之一。单独暴露于亚硝酸盐8周后会导致脊髓轴突乙酰胆碱酯酶活性降低,而联合暴露仅在8周时出现此效应,随后消失。在整个研究过程中,联合暴露组的轴突琥珀酸脱氢酶活性低于对照组,联合暴露还导致肌肉肌酸激酶活性持续升高。吗啉诱导的效应不太显著。结果表明溶剂和亚硝酸盐之间存在药代动力学相互作用,且各自对能量代谢有影响。虽然不能排除其他代谢相互作用,但未发现N-亚硝基吗啉。