[Subchronic oral toxicity study of cyanoguanidine in F344 rats].
A 13-week subchronic oral toxicity study of cyanoguanidine was performed in male and female F344 rats by feeding of CRF1 powder diets containing 0, 1.25, 2.5, 5 and 10% cyanoguanidine to determine appropriate dose levels for a subsequent 2-year carcinogenicity study. The rats were randomly allocated to 5 groups, each consisting of 10 males and 10 females. No animals died during the administration period. Inhibition of body weight gain was more marked in both sexes of the 10% group and in females of the 5% group as compared with the control group. Mean food intake in males of the groups treated with 5% or 10% and in females of the 10% group was significantly higher than that in the control group. Serum biochemical investigation revealed a higher level of serum BUN in both sexes of the 10% group. On histopathological examination, toxic changes characterized by the occurrence of intranuclear eosinophilic inclusion bodies in the proximal tubular epithelium of the kidney were observed in both sexes of the 10% group. Similar inclusion bodies were also seen in 2 out of 10 males of the 5% group. From these results, it was concluded that a level of 10% of cyanoguanidine in the diet is unequivocally toxic. A dose level, 5% cyanoguanidine, in the diet might be appropriate as a high dose for a carcinogenicity study.
Y
Y
Matsushima
H
H
Onodera
H
H
Ogasawara
K
K
Kitaura
K
K
Mitsumori
A
A
Maekawa
M
M
Takahashi
D000284:Administration, Oral; D000818:Animals; D005260:Female; D006146:Guanidines / Q000008:administration & dosage / Q000633:toxicity*; D006403:Hematologic Tests; D008297:Male; D009929:Organ Size / Q000187:drug effects; D011897:Random Allocation; D051381:Rats; D011916:Rats, Inbred F344; D013997:Time Factors
D006146:Guanidines; C004711:dicyandiamido