Developmental toxicity evaluation of gallium nitrate in mice.
Gallium nitrate, a drug with antitumor activity, is presently undergoing clinical trials as a chemotherapeutic agent for the treatment of certain malignancies. Since there are very limited published animal toxicity data available, this study was conducted to investigate the potential adverse developmental effects of this drug. Pregnant Swiss mice were administered intraperitoneally gallium nitrate at 12.5, 25, 50, and 100 mg/kg/day on days 6, 8, 10, 12, and 14 of gestation. Monitors for maternal toxicity were body weight, food consumption and clinical signs. At sacrifice (day 18) maternal weight, liver and kidney weights, and gravid uterine weights were measured. Gestational parameters monitored were numbers of total implants, resorptions, postimplantation losses, and dead fetuses. Live fetuses were sexed, weighted, and examined for external, internal and skeletal malformations and variations. Maternal toxicity was noted in all the gallium nitrate-treated groups. Embryo/fetal toxicity was evidenced by a decrease in the number of viable implants, a reduction in fetal weight, and an increase in the number of skeletal variations (12.5, 25, 50 and 100 mg/kg). No significant increase in the incidence of malformations was observed at 12.5, 25, or 50 mg/kg. The no-observable-adverse-effect level (NOAEL) for both maternal and developmental toxicity of gallium nitrate was less than 12.5 mg/kg.
Gómez
M
M
Laboratory of Toxicology and Biochemistry, School of Medicine, University of Barcelona, Reus, Spain.
Sánchez
D J
DJ
Domingo
J L
JL
Corbella
J
J
D000014:Abnormalities, Drug-Induced / Q000209:etiology*; D000818:Animals; D000970:Antineoplastic Agents / Q000633:toxicity*; D001835:Body Weight / Q000187:drug effects; D005314:Embryonic and Fetal Development / Q000187:drug effects*; D005260:Female; D005708:Gallium / Q000633:toxicity*; D008297:Male; D051379:Mice; D011247:Pregnancy
D000970:Antineoplastic Agents; D005708:Gallium; C027235:gallium nitrate