Showing papers in "Journal of the American Pharmaceutical Association in 1939"

Studies on the Toxicity of Diethylene Glycol, Elixir of Sulfanilamide-Massengill and a Synthetic Elixir

Abstract: Shortly after the unfortunate introduction and use of the so-called “Elixir of Sulfanilamide-Massengill,” with its lethal effects in nearly a hundred instances, there appeared in the literature numerous papers (l), (2), (3), (4), (5) which clearly indicated that the solvent used, diethylene glycol, was the chief toxic agent present in the “Elixir.” Prior to this time the literature contained few papers dealing with the toxicity of this substance. Von Oettingen and Jirouch (6) found that subcutaneous injections of 2.5 to 5.0 cc. per Kg. of a 50% aqueous solution of diethylene glycol into rats produced severe kidney damage. Larger doses (10 cc. per Kg.) caused a marked filling of intracapsular spaces and tubules with blood, in addition to degenerative processes. Lepkovsky, Ouer and Evans (7) found that the substitution of diethylene glycol esters of fatty acids for the natural or synthetic glycerol esters in the diets of rats resulted in death of the animals after about three weeks when the glycol ester content of the diet was 60%. Effects of concentrations less than 60% were not reported. The pathology seen on microscopic examinations of organs from these animals was essentially the same as that mentioned briefly by von Oettingen and Jirouch, and recently described in more detail by Kesten, Mulinos and Pomerantz (1) and Cannon (4). Haag and Ambrose (8) found the following fatal doses in acute experiments on rats: intravenous 5 cc. per Kg. (80 % mortality), intramuscular 7 cc. (80% mortality), subcutaneous 15 cc. (60% mortality) and oral 15 cc. (100% mortality); and on rabbits: intravenous 2 cc. (60% mortality) and intramuscular 4 cc. (80% mortality). Haag and Ambrose also noted that concentrations of diethylene glycol of 1% or less caused no significant variation in rate of growth, or damage to internal organs of rats which were examined at the end of the experimental period of 100 days. Concentrations of 3y0 and 10% in the drinking water rapidly proved fatal. Kesten, et al., obtained essentially the same results: concentrations of 1% or less produced no discernible pathology, whereas concentrations of 3% or more resulted in death of many of the animals in periods varying from one day to about two months. Not all rats were equally susceptible, as indicated by the fact that nearly half the group which received 3% diethylene glycol showed neither kidney nor liver lesions after they had received the glycol for longer periods than others in the same group which died from extensive kidney damage. Holck (2) found that drinking water containing 5% commercial diethylene glycol was fatal within a period of 11 days to a group of five rats (average duration of life for the whole group was 8 days). In a similar experiment in which drinking water contained 4% pure diethylene glycol, three of the group of five rats died within 9 days, but the two remaining animals survived for the duration of the experiment-nine weeks. At all concentrations of pure glycol of 0.25% or more there was a definite retardation of growth. Only a t a concentration of O.l25y0 was