Evaluation of 13-Week Repeated-Dose Oral Toxicity of Zirconium(iv) Butoxide in Crl:CD(SD) Rats.

Zirconium(IV) butoxide (ZB; CAS 1071-76-7) is widely used in industrial applications as a catalyst, stabilizer, and precursor for ceramic materials utilized in medical devices such as artificial bones and teeth. Metal alkoxide compounds, including ZB, are easily hydrolyzed, polymerized, and precipitated in aqueous environments. Although a no-observed-adverse-effect level (NOAEL) for ZB has been estimated by extrapolating its hydrolysis product, 1-butanol, ZB toxicological profile remains unclear, leaving data gaps for risk evaluation. In this study, we developed a method for ZB preparation and administration using corn oil as vehicle, in which ZB was retained its polymerizable form. A 13-week repeated-dose oral toxicity study was conducted in 6-week-old Crl:CD(SD) rats. Groups of ten males and females were orally administered ZB at doses of 0 (vehicle: corn oil), 100, 300, and 1000 mg/kg body weight (bw)/day, or 1-butanol at 116 mg/kg bw/day, which was equivalent to its level after dosing ZB at 1000 mg/kg bw/day. No toxicologically significant effects were observed after ZB administration. The NOAEL for ZB was estimated to be 1000 mg/kg bw/day in both sexes. These results provide essential toxicological data for safety assessment and regulatory evaluation of ZB.