Seventy-eight-week dietary carcinogenicity study of (+/-)-4-diethylamino-1,1-dimethylbut-2-yn-1-yl 2-cyclohexyl-2-hydroxy-2-phenylacetate monohydrochloride monohydrate (NS-21), a novel drug for urinary frequency and incontinence, in mice.
The oncogenic potential of (+/-)-4-diethylamino-1,1-dimethylbut-2-yn-1-yl 2-cyclohexyl-2-hydroxy-2-phenylacetate monohydrochloride monohydrate (NS-21), a new drug for the treatment of urinary frequency and incontinence, was assessed when it was administered in the diet of Charles River B6C3F1 mice for 78 weeks in dosages of 0, 30, 100 and 300 mg/kg/day. No drug-related effects occurred on survival, appearance or behavior, or occurrence, location or number of palpable masses. Average food consumption, food efficiency and hematologic values also were apparently unaffected. Statistically significantly low body weights were observed in the 100 and 300 mg/kg/day mice. The plasma concentrations of NS-21 and its active metabolite, RCC-36, in the treated groups were increased in a dose-dependent manner. Histopathological examinations disclosed midzonal hepatocellular vacuolization compatible with lipid vacuoles in both sexes at the 300 mg/kg/day dose level. There were no test article-related effects on the incidence or type of neoplastic lesions. In conclusion, under the conditions of this study, no oncogenic effects were evident in B6C3F1 mice when NS-21 was administered in the diet in concentrations to produce an intake of up to 300 mg/kg/day for 78 weeks.
Hatch
R C
RC
MPI Research (Formerly International Research and Development Corporation), Mattawan Michigan 49071, USA.
Regan
K S
KS
Ishibashi
S
S
Nakazawa
M
M
Iwakura
K
K
Sumi
N
N
D000284:Administration, Oral; D000818:Animals; D015197:Carcinogenicity Tests; D002273:Carcinogens / Q000633:toxicity*; D004032:Diet; D005260:Female; D008297:Male; D051379:Mice; D015394:Molecular Structure; D010648:Phenylacetates / Q000008:administration & dosage / Q000627:therapeutic use / Q000633:toxicity*; D013997:Time Factors; D014549:Urinary Incontinence / Q000188:drug therapy; D014555:Urination Disorders / Q000188:drug therapy*
D002273:Carcinogens; D010648:Phenylacetates; C105354:temiverine