[Reproductive and developmental toxicity study of gadobenate dimeglumine formulation (E7155) (3)--Study of embryo-fetal toxicity in rabbits by intravenous administration].
Gadobenate dimeglumine formulation (E7155) was daily administered by intravenous injection at 0.3, 0.9 or 2.0 mmol/kg/day to mated NZW female rabbits (20/group) to assess the effect on embryo-fetal development. Treatment with 2.0 mmol/kg/day caused initial, notable loss of body weight and reduction in food consumption. Slightly reduced body weight gain and food intake were recorded at 0.9 mmol/kg/day. There were no obvious adverse effects in dams given E7155 at 0.3 mmol/kg/day. There was a slightly higher incidence of early intrauterine deaths at 0.9 and 2.0 mmol/kg/day. Morphological examination of fetuses at 2.0 mmol/kg/day revealed small eye/microphthalmia and/or retinal irregularities in three fetuses from three separate litters. There was also an increase in the incidence of additional and/or fused sternebral centres and 20-thoracolumbar vertebrae at this dosage. From these results, the No Observed Adverse Effect Level (NOAEL) for general toxicity of dams and embryo-fetal development was 0.3 mmol/kg/day.
Okuda
Y
Y
Department of Developmental Safety Assessment Research, Eisai Co., Ltd., Gifu, Japan.
Sagami
F
F
Tirone
P
P
Morisetti
A
A
Bussi
S
S
Masters
R E
RE
D000014:Abnormalities, Drug-Induced / Q000209:etiology; D000818:Animals; D001835:Body Weight / Q000187:drug effects; D003287:Contrast Media / Q000633:toxicity*; D004622:Embryo, Mammalian / Q000187:drug effects*; D005260:Female; D005313:Fetal Death / Q000139:chemically induced; D005333:Fetus / Q000187:drug effects*; D005682:Gadolinium / Q000633:toxicity*; D007275:Injections, Intravenous; D008279:Magnetic Resonance Imaging; D008536:Meglumine / Q000031:analogs & derivatives* / Q000633:toxicity; D009942:Organometallic Compounds / Q000633:toxicity*; D011817:Rabbits; D013723:Teratogens
D003287:Contrast Media; D009942:Organometallic Compounds; D013723:Teratogens; C064572:gadobenic acid; D008536:Meglumine; D005682:Gadolinium