title: Common nature in the effects of thalidomide on embryo-fetal development in Kbl:JW and Kbl:NZW rabbits.
abstract: The effects of thalidomide on the embryo-fetal development (EFD) of rabbit fetuses and the sensitive periods (SP) for the various malformations were compared between Kbl:JW and Kbl:NZW rabbits to investigate possible strain differences. The post-implantation loss rate and number of placental remnants were increased and the number of live fetuses was decreased in both of the strains in the EFD study and in Kbl:NZW at 300 mg/kg dosed on GD 7-8 in the SP study. In the external and skeletal examinations, head, limb and tail malformations were observed in both the strains in the EFD and SP studies at the same dose levels in the same dosing period. In the visceral examination, hydrocephaly, cardiovascular malformations, absent pulmonary intermedial lobe, diaphragmatic hernia and/or abnormal liver lobation were also observed in both of the strains in the EFD and SP studies at the same dose levels and in the same dosing period. Plasma concentrations of thalidomide were equivalent between the two strains in the SP study. There were strain differences in some parameters, such as the post-implantation loss rate and the frequencies of malformations in forelimb and hindlimb and pulmonary intermedial lobe, but similar types of malformations or variations were induced at the same dose levels on the same dosing period in both strains. Therefore, it is concluded that there were no essential differences in sensitivity of the fetuses to thalidomide between Kbl:JW and NZW rabbits and both of the strains are useful to evaluate the teratogenic effects of thalidomide.
authors.affiliation: Drug Safety Research Laboratories, Pharmaceutical Research Division, Takeda Pharmaceutical Company Limited, Fujisawa, Kanagawa, Japan.
authors.forename: Yoshinori
authors.initials: Y
authors.lastname: Kawamura
authors.forename: Yasuki
authors.initials: Y
authors.lastname: Shirotsuka
authors.forename: Hirofumi
authors.initials: H
authors.lastname: Awatsuji
authors.forename: Kiyoshi
authors.initials: K
authors.lastname: Matsumoto
authors.forename: Keiichiro
authors.initials: K
authors.lastname: Sato
mesh_terms: D000014:Abnormalities, Drug-Induced / Q000235:genetics / Q000503:physiopathology*; D000818:Animals; D004305:Dose-Response Relationship, Drug; D004622:Embryo, Mammalian / Q000002:abnormalities*; D047108:Embryonic Development / Q000187:drug effects*; D005260:Female; D047109:Fetal Development / Q000187:drug effects; D006801:Humans; D018811:Maternal Exposure; D011247:Pregnancy; D011817:Rabbits; D013723:Teratogens / Q000633:toxicity; D013792:Thalidomide / Q000633:toxicity*
chemical_list: D013723:Teratogens; D013792:Thalidomide
keywords: Kbl:JW; Kbl:NZW; embryo-fetal development; rabbit; thalidomide