Some Toxic Properties of Dimethylnitrosamine

Abstract

The appearance of two cases of cirrhosis of the liver among three men working in the research laboratory of a large industrial undertaking led to suspicion becoming attached to dimethylnitrosamine (D.M.N.) as the causative agent. Dimethylnitro samine had been introduced into the laboratory as a solvent about 10 months before the first case of cirrhosis was discovered. One of the men had died of bronchopneumonia, and cirrhosis of the liver was an incidental finding at necropsy. The second man with a long-standing history of dyspepsia had a laparotomy after five months' exposure to D.M.N. At that time no note of any abnormality of the liver was made. Six months later he was examined for an incisional hernia that had developed in the operation scar, it was then recorded that the liver felt hard and was suspected of being cirrhotic. Liver function tests carried out at this time showed evidence of damage. When repeated thfee months later after all further exposure to D.M.N. had ceased these tests indicated an improved liver function. The third man has remained in good health but has had no liver function tests carried out on him. A search of the literature revealed only a single short report of the toxic properties of D.M.N. (Hamilton and Hardy, 1949). Dimethylnitrosamine had been used in an automobile factory and some illness had followed. Experiments on dogs showed it to be capable of producing severe liver injury, but no experimental details are provided. The medical officer of the firm therefore asked if we would examine the toxic properties of D.M.N. towards laboratory animals. CH Dimethylnitrosamine, ^tT3 >N.NO, is a mobile CH3/ yellow liquid with a faint, characteristic odour. It boils at 151? C. and its specific gravity is 1-015 at 20? C. It is miscible in all proportions with water, ethyl alcohol, m?thyl?ne chloride, or vegetable oil. Under ordinary conditions it is a stable substance, but with zinc dust and acetic acid it can be reduced CH to dimethylhydrazine rLr3)N.NH,. CJ-I3/ Preliminary experiments revealed that D.M.N. readily produced a severe liver injury and this paper gives an account of some of the features of the lesions. Materials and Methods