Carcinogenicity studies with medroxalol hydrochloride in rats and mice.
The carcinogenic potential of medroxalol hydrochloride, an antihypertensive agent with beta 1 adrenergic cardiac blocking properties, and beta 2 and some alpha 1 vasodilating activity, was studied by dietary administration. Long Evans rats were treated for 2 years and CD-1 mice for 18 months at dosages of 0, 50, 250 or 500 mg/kg/day. Medroxalol did not produce any evidence of a tumorigenic effect in the Long Evans rat, but graying of pigmented hair was noted at 250 and 500 mg/kg/day and is probably related to melanin binding of the drug. In the CD-1 mouse, there was a dose related increase in uterine leiomyomas that was statistically significant (p less than 0.05) at doses of 250 and 500 mg/kg/day. The incidence at 50 mg/kg/day was not different from control. Endometrial stromal sarcomas were observed only in treated mice, and pairwise comparison with controls indicated a statistically significant difference (p less than 0.05) only at the lowest dosage (50 mg/kg/day). The latter finding may not be related to treatment since there was no dose response and the incidence in the two higher dose groups was neither statistically significant nor higher than occasionally seen in other control groups.
Merrell Dow Research Institute, Merrell Dow Pharmaceuticals, Cincinnati, Ohio 45215.
D M
DM
Sells
J P
JP
Gibson
D000818:Animals; D001835:Body Weight / Q000187:drug effects; D004305:Dose-Response Relationship, Drug; D004983:Ethanolamines / Q000633:toxicity*; D005260:Female; D008297:Male; D051379:Mice; D009374:Neoplasms, Experimental / Q000139:chemically induced*; D051381:Rats; D012737:Sex Factors
D004983:Ethanolamines; C024892:medroxalol