[Reproductive and developmental toxicity study of mofezolac (N-22) (1)--Study by oral administration of N-22 prior to and early stages of pregnancy in rats].
Mofezolac (N-22), a newly developed analgesic and anti-inflammatory agent, at dose levels of 0, 10, 30 and 90 mg/kg/day were administered orally to males from pre-mating to mating period and to females from pre-mating to early gestation period. Effects on reproductive performance of both sexes, especially reproductive capability, and development of offspring were examined. 1. In male parents, no changes in body weight and food consumption were found in all male groups, but the increase in gastric mucosal lesions such as ulcers were observed in 30 and 90 mg/kg/day groups. 2. In female parents, the decrease in body weight and food consumption of 90 mg/kg/day group during early gestation period were found, but at necropsy no changes were shown in all female groups. 3. Reproductive capability, mating and pregnancy performance were not affected. 4. No effects of N-22 on fetuses were observed. 5. The suggestions were as follows: No effect dose levels (NOELs) for male and female general-toxicologically were 10 and 30 mg/kg/day, respectively. NOELs for reproductive capability and for fetal development were 90 mg/kg/day.
Yamakita
O
O
Drug Safety Laboratory, Taiho Pharmaeutical Co., LTD., Tokushima-shi, Japan.
Koida
M
M
Shinomiya
M
M
Katayama
S
S
Ikebuchi
K
K
Yoshida
R
R
D000284:Administration, Oral; D000818:Animals; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000008:administration & dosage / Q000633:toxicity*; D005314:Embryonic and Fetal Development / Q000187:drug effects; D005260:Female; D005298:Fertility / Q000187:drug effects; D007555:Isoxazoles / Q000008:administration & dosage / Q000633:toxicity*; D008297:Male; D011247:Pregnancy; D011270:Pregnancy, Animal / Q000187:drug effects*; D051381:Rats; D011919:Rats, Inbred Strains; D012098:Reproduction / Q000187:drug effects*
D000894:Anti-Inflammatory Agents, Non-Steroidal; D007555:Isoxazoles; C054999:mofezolac