左甲状腺素合成杂质既无诱变性也无遗传毒性：Insilico、Ames 试验和微核试验研究

IF 2.3 4区医学 Q3 BIOTECHNOLOGY & APPLIED MICROBIOLOGY Mutation research. Genetic toxicology and environmental mutagenesis Pub Date : 2024-08-01 DOI:10.1016/j.mrgentox.2024.503796

Rajesh Rane , Akshay Prabhune , Dileep Kumar , Ajay Kumar , Madhur Sewlikar , Mugdha Suryawanshi , Bharat Satpute , Bapu Gawade , Sachin Sakat

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引用次数: 0

摘要

采用体外试验和硅学试验来评估左甲状腺素（一种用于甲状腺激素替代疗法的药物）中可能存在的五种杂质可能具有的遗传毒性和诱变性。无论是 ToxTree 还是 VEGA（在全球架构内评估化学品特性的虚拟模型）都没有发现任何一种杂质值得关注。阿姆斯试验结果（每平板剂量最高为 1 毫克），无论是否有新陈代谢活化，均为阴性。用 TK6（人淋巴母细胞）细胞进行的微核试验（剂量不超过 500 微克/毫升），无论是否进行了新陈代谢活化，结果也是阴性。

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Levothyroxine synthesis impurities are neither mutagenic nor genotoxic: Insilico, Ames test and micronucleus test studies

In vitro and in silico tests were used to assess the possible genotoxicity and mutagenicity of five impurities that may be present in levothyroxine, a drug used for thyroid hormone replacement therapy. Neither ToxTree nor VEGA (Virtual Models for evaluating the properties of chemicals within a global architecture) identified cause for concern for any of the impurities. Ames test results (doses up to 1 mg per plate), with or without metabolic activation, were negative. The micronucleus test with TK6 (human lymphoblastoid) cells, at doses up to 500 µg/mL, with or without metabolic activation, also gave negative results.

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来源期刊

Mutation research. Genetic toxicology and environmental mutagenesis 生物-毒理学

CiteScore

3.80

自引率

5.30%

发文量

审稿时长

105 days

期刊介绍： Mutation Research - Genetic Toxicology and Environmental Mutagenesis (MRGTEM) publishes papers advancing knowledge in the field of genetic toxicology. Papers are welcomed in the following areas: New developments in genotoxicity testing of chemical agents (e.g. improvements in methodology of assay systems and interpretation of results). Alternatives to and refinement of the use of animals in genotoxicity testing. Nano-genotoxicology, the study of genotoxicity hazards and risks related to novel man-made nanomaterials. Studies of epigenetic changes in relation to genotoxic effects. The use of structure-activity relationships in predicting genotoxic effects. The isolation and chemical characterization of novel environmental mutagens. The measurement of genotoxic effects in human populations, when accompanied by quantitative measurements of environmental or occupational exposures. The application of novel technologies for assessing the hazard and risks associated with genotoxic substances (e.g. OMICS or other high-throughput approaches to genotoxicity testing). MRGTEM is now accepting submissions for a new section of the journal: Current Topics in Genotoxicity Testing, that will be dedicated to the discussion of current issues relating to design, interpretation and strategic use of genotoxicity tests. This section is envisaged to include discussions relating to the development of new international testing guidelines, but also to wider topics in the field. The evaluation of contrasting or opposing viewpoints is welcomed as long as the presentation is in accordance with the journal''s aims, scope, and policies.