背景:叔丁基过氧化氢(TBHP;CAS75-91-2),氢过氧化物,主要用作聚合引发剂生产聚乙烯,聚氯乙烯,和不饱和聚酯。它是一种高产化学品,在工业国家广泛使用,包括日本。TBHP还用作制造食品器具的添加剂,容器,和包装(UCP)。因此,消费者可能通过口服摄入从UCP洗脱的TBHP而暴露。在各种体外和体内遗传毒性测定中研究了TBHP。在艾姆斯测试中,一些阳性结果有和/或无代谢激活.至于小鼠淋巴瘤检测,报告了阳性结果,无论是否存在代谢活化酶。一些染色体畸变试验和体外彗星试验的结果也证明了遗传毒性阳性结果。另一方面,在体内测试中,通过单次静脉注射给予TBHP的小鼠的骨髓微核试验和通过吸入暴露于TBHP5天的大鼠的骨髓染色体畸变试验均为阴性。此外,关于显性致死试验,基因毒性阳性结果出现.相比之下,关于体内致突变性的信息很少,关于口服暴露的致癌性也没有信息。
结果:我们根据OECD化学品测试指南使用MutaMice进行了体内基因突变测定。488通过口服暴露研究TBHP的体内诱变性。反复给药28天后,高达300mg/kg/天(接近最大耐受剂量(MTD))的肝脏和腺胃的突变频率(MFs)没有显着差异。阳性和阴性对照产生预期的反应。
结论:这些发现表明,在这些实验条件下,口服给药的TBHP在小鼠肝脏和腺胃中没有致突变性。
BACKGROUND: tert-Butyl hydroperoxide (
TBHP; CAS 75-91-2), a hydroperoxide, is mainly used as a polymerization initiator to produce polyethylene, polyvinyl chloride, and unsaturated polyester. It is a high-production chemical, widely used in industrial countries, including Japan.
TBHP is also used as an additive for the manufacturing of food utensils, containers, and packaging (UCP). Therefore, there could be consumer exposure through oral intake of
TBHP eluted from UCPs.
TBHP was investigated in various in vitro and in vivo genotoxicity assays. In Ames tests, some positive results were reported with and/or without metabolic activation. As for the mouse lymphoma assay, the positive result was reported, regardless of the presence or absence of metabolic activation enzymes. The results of some chromosomal aberrations test and comet assay in vitro also demonstrated the genotoxic positive results. On the other hand, in in vivo tests, there are negative results in the bone marrow micronucleus test of TBHP-administered mice by single intravenous injection and the bone marrow chromosomal aberration test using rats exposed to
TBHP for 5 days by inhalation. Also, about dominant lethal tests, the genotoxic positive results appeared. In contrast, there is little information about in vivo mutagenicity and no information about carcinogenicity by oral exposure.
RESULTS: We conducted in vivo gene mutation assay using MutaMice according to the OECD Guidelines for the Testing of Chemicals No. 488 to investigate in vivo mutagenicity of TBHP through oral exposure. After repeated dosing for 28 days, there were no significant differences in the mutant frequencies (MFs) of the liver and glandular stomach up to 300 mg/kg/day (close to the maximum tolerable dose (MTD)). The positive and negative controls produced the expected responses.
CONCLUSIONS: These findings show that orally administrated TBHP is not mutagenic in the mouse liver and glandular stomach under these experimental conditions.