Developmental toxicity evaluation of gallium nitrate in mice

Abstract

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.

Transcriptomic Analysis of Shiga Toxin-Producing Escherichia coli FORC_035 Reveals the Essential Role of Iron Acquisition for Survival in Canola Sprouts and Water Dropwort

“…Biofilms enable bacteria to resist stressful conditions such as disinfectants and the defense responses of plants and animals, which makes biofilms an important issue to deal with in food hygiene ( Srey et al, 2013 ). Gallium was approved for hypercalcemia treatment by the FDA, and has low toxicity at appropriate doses ( Chitambar and Narasimhan, 1991 ; Gómez et al, 1992 ). The inhibitory effects of gallium on bacterial growth and biofilm formation suggest that gallium can potentially be used as an antimicrobial agent.…”

“…Ga(NO 3 ) 3 dissolved in sterile water was added at different concentrations when needed. Considering no-observable-adverse-effect level (NOAEL) and acceptable-daily-intake (ADI) values of gallium, Ga(NO 3 ) 3 was used up to 1 mM ( Gómez et al, 1992 ). Biofilm formation was quantified by staining with 0.1% crystal violet for 5 min followed by washing with phosphate buffer (0.1 M, pH 7.4).…”

Gallium

“…Gallium compounds have been shown to induce developmental defects in animal studies. Gomez et al (1992) administered Ga(NO 3 ) 3 intraperitoneally to pregnant Swiss mice at 12.5, 25, 50, and 100 mg kg À1 day À1 on days 6, 8, 10, 12, and 14 of gestation. Maternal toxicity was noted in all treated groups.…”

Valorization of GaN based metal-organic chemical vapor deposition dust a semiconductor power device industry waste through mechanochemical oxidation and leaching: A sustainable green process

“…Health hazard of gallium and gallium compounds includes metallic taste, dermatitis, depression of the bone marrow function and large doses may cause hemorrhagic nephritis (Dierks, 2013). Domingo et al, and Gomez et al have reported acute toxicity of gallium in rats and mice ( [Colomina et al, 1993,Domingo et al, 1987,Gómez et al, 1992). One should not be confused with bulk GaN non-toxicity.…”