Evaluation of 13-week repeated-dose oral toxicity of zirconium(IV) butoxide in Crl:CD(SD) rats

IF 4.3 4区医学 Q1 MEDICINE, LEGAL

Regulatory Toxicology and Pharmacology Pub Date : 2026-01-01 Epub Date: 2025-10-21 DOI:10.1016/j.yrtph.2025.105968

Yasumasa Murata , Jun-ichi Akagi , Yuko Doi , Takako Iso , Takaaki Umano , Kenichi Masumura , Mariko Matsumoto , Takeshi Toyoda , Kumiko Ogawa

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引用次数: 0

Abstract

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.

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丁二氧化锆（IV）对CD（SD）大鼠13周重复剂量口服毒性评价。

丁二氧化锆（ZB; CAS 1071-76-7）作为催化剂、稳定剂和前驱体广泛应用于医疗器械（如人造骨和牙齿）的陶瓷材料。金属醇氧化合物，包括ZB，在水环境中很容易水解、聚合和沉淀。虽然通过外推其水解产物- 1-丁醇估计了ZB的无观察到的不良反应水平（NOAEL），但ZB的毒理学特征仍不清楚，为风险评估留下了数据空白。在本研究中，我们开发了一种以玉米油为载体的ZB制备和给药方法，该方法保留了ZB的可聚合形式。对6周龄大鼠进行了为期13周的重复给药口服毒性研究。每组10只雄性和雌性分别口服剂量为0、100、300和1,000 mg/kg体重(bw)/天的ZB（对照剂：玉米油），或剂量为116 mg/kg体重/天的1-丁醇，其剂量与ZB剂量为1,000 mg/kg体重/天后的水平相当。ZB给药后未见明显毒理学效应。两性对ZB的NOAEL估计为1,000 mg/kg bw/day。这些结果为ZB的安全性评价和监管评价提供了必要的毒理学数据。

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来源期刊

Regulatory Toxicology and Pharmacology 医学-毒理学

CiteScore

6.70

自引率

8.80%

发文量

147

审稿时长

58 days

期刊介绍： Regulatory Toxicology and Pharmacology publishes peer reviewed articles that involve the generation, evaluation, and interpretation of experimental animal and human data that are of direct importance and relevance for regulatory authorities with respect to toxicological and pharmacological regulations in society. All peer-reviewed articles that are published should be devoted to improve the protection of human health and environment. Reviews and discussions are welcomed that address legal and/or regulatory decisions with respect to risk assessment and management of toxicological and pharmacological compounds on a scientific basis. It addresses an international readership of scientists, risk assessors and managers, and other professionals active in the field of human and environmental health. Types of peer-reviewed articles published: -Original research articles of relevance for regulatory aspects covering aspects including, but not limited to: 1.Factors influencing human sensitivity 2.Exposure science related to risk assessment 3.Alternative toxicological test methods 4.Frameworks for evaluation and integration of data in regulatory evaluations 5.Harmonization across regulatory agencies 6.Read-across methods and evaluations -Contemporary Reviews on policy related Research issues -Letters to the Editor -Guest Editorials (by Invitation)