title: [Reproductive and developmental toxicity study of mofezolac (N-22) (2)--Study by oral administration of N-22 during the period of fetal organogenesis in rats].
abstract: The teratogenicity of mofezolac (N-22), a new developed analgesic and anti-inflammatory agent, was investigated in rats. N-22 was given orally to pregnant rats of the Jcl: Wistar strain (30 rats per group) at dose levels of 10, 50, 100 and 150 mg/kg/day from days 7 to 17 of gestation. Caesarean sections were performed on 20 dams per group on day 20 of gestation and their fetuses were examined for external, visceral and skeletal abnormalities. The remaining 10 dams per group were allowed to deliver and their offspring were examined for growth and reproductive performance. Results were as follows. 1. Effects on F0 generation At 150 mg/kg, eleven out of the 30 dams exhibited decreased motor activity, pale eyes, unkempt fur, urine-smeared lower abdomen, weakness and emaciation. At autopsy, twelve dams revealed gastrointestinal ulcers, peritonitic lesions, hypertrophy of the spleen, adrenal and mesenteric lymph node, atrophy of the submaxillary gland, thymus and liver and discoloration of the liver and kidney. Death, sacrificing in extremis, premature or delayed delivery and poor nursing occurred in one to two dams each. Food consumption was significantly decreased and body weight gain was significantly retarded in this dose level group. At 100 mg/kg, urine-smeared lower abdomen, hypertrophy of the spleen and poor nursing were observed in one dam each. 2. Effects on F1 generation At 150 mg/kg, significantly decreased fetal weight, increased number of immature fetuses and significantly retarded ossification of the 5th and 6th sternebrae and coccygeal vertebrae as well as significantly depressed body weight gain of female offspring were observed. No abnormalities were observed in each treated group in terms of development, behavior, learning ability and reproductive performance of offspring. 3. Effects on F2 generation No abnormalities were observed in fetuses and newborn young in each treated group. Based on these results, the maximum non-effective doses of N-22 in this study were considered to be 50 mg/kg/day for dams and offspring and 100 mg/kg/day for fetuses.
authors.affiliation: Biological Research Center for the Protection of Environment, Shiga, Japan.
authors.forename: I
authors.initials: I
authors.lastname: Toteno
authors.forename: S
authors.initials: S
authors.lastname: Haguro
authors.forename: S
authors.initials: S
authors.lastname: Furukawa
authors.forename: T
authors.initials: T
authors.lastname: Morinaga
authors.forename: K
authors.initials: K
authors.lastname: Morino
authors.forename: S
authors.initials: S
authors.lastname: Fujii
authors.forename: O
authors.initials: O
authors.lastname: Yamakita
mesh_terms: D000014:Abnormalities, Drug-Induced / Q000209:etiology*; D000284:Administration, Oral; D000818:Animals; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000008:administration & dosage / Q000633:toxicity*; D003050:Coccyx / Q000002:abnormalities; D005314:Embryonic and Fetal Development / Q000187:drug effects*; D005260:Female; D005865:Gestational Age; D007555:Isoxazoles / Q000008:administration & dosage / Q000633:toxicity*; D011247:Pregnancy; D051381:Rats; D011919:Rats, Inbred Strains; D012098:Reproduction / Q000187:drug effects*; D013249:Sternum / Q000002:abnormalities
chemical_list: D000894:Anti-Inflammatory Agents, Non-Steroidal; D007555:Isoxazoles; C054999:mofezolac