Production of Thyroid Hyperplasia in Rats and Mice by Administration of Methyl Cyanide

The daily subcutaneous administration of small doses of aliphatic cyanides to young rabbits of either sex maintained on a diet of alfalfa hay and oats has been shown to produce thyroid hyperplasia within 21 days. 1 The most potent cyanide was found to be methyl cyanide. The use of methyl cyanide as a goitrogenic agent has now been extended to rats and mice.

Rats. Twelve female albino rats, 6 being litter mates aged 3 months, and 6 litter mates aged 5 months, were divided into 3 groups, 2 animals from each litter comprising each group. Their diet consisted of hominy 100 parts, rolled oats 25 parts, powdered skim milk 5 parts, dry meat 25 parts, salt 1 1/2 parts and tap water; this was found to be nongoitrogenic They were given daily subcutaneous injections of varying doses of methyl cyanide in water, the first group receiving 0.08 cc, the second 0.04 cc. and the third 0.02 cc. of methyl cyanide. One animal from each group was sacrificed at the end of 21 days, and all showed only very slight thyroid hyperemia. At the end of 28 days there was definite thyroid hypertrophy, but it was obvious that rats' thyroids were less reactive than rabbits'. During the next 8 days the doses were gradually increased on the remainder in each group, until that on the largest dose was receiving as much as 0.15 cc. of methyl cyanide daily without any clinical sign of cyanide poisoning. After 36 days of treatment the thyroids were larger and more hyperemic. As has been pointed out previously, there were individual variations, but in general the thyroid reactions were proportional to dosage. The results are given in Table I.