Mutagenicity assessment of two potential impurities in preparations of 5-amino-2,4,6 triiodoisophthalic acid, a key intermediate in the synthesis of the iodinated contrast agent iopamidol

IF 2.3 4区医学 Q3 BIOTECHNOLOGY & APPLIED MICROBIOLOGY

Mutation research. Genetic toxicology and environmental mutagenesis Pub Date : 2023-11-28 DOI:10.1016/j.mrgentox.2023.503720

Silvia Rossi , Simona Bussi , Roberta Bonafè , Carola Incardona , Emanuela Vurro , Massimo Visigalli , Federica Buonsanti , Roberta Fretta

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引用次数: 0

Abstract

5-Aminoisophthalic acid and 5-nitroisophthalic acid (5-NIPA) are potential impurities in preparations of 5-amino-2,4,6-triiodoisophthalic acid, which is a key intermediate in the synthesis of the iodinated contrast agent iopamidol. We have studied their mutagenicity in silico (quantitative structure-activity relationships, QSAR) and by the bacterial reverse mutation assay (Ames test). First, the compounds were screened with the tools Derek Nexus™ and Leadscope®. Both compounds were flagged as potentially mutagenic (class 3 under ICH M7). However, contrary to the in silico prediction, neither chemical was mutagenic in the Ames test (plate incorporation method) with or without S9 metabolic activation.

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碘化造影剂iopamidol合成中的关键中间体- 5-氨基-2,4,6三碘二苯二甲酸制备中两种潜在杂质的致突变性评价

5-氨基间苯二甲酸和5-硝基间苯二甲酸(5-NIPA)是合成碘化造影剂iopamidol的关键中间体5-氨基-2,4,6-三碘间苯二甲酸的潜在杂质。我们用定量构效关系(QSAR)和细菌反向突变试验(Ames试验)研究了它们的致突变性。首先，使用Derek Nexus™和Leadscope®工具筛选化合物。这两种化合物都被标记为潜在的致突变性(ICH M7中的3类)。然而，与计算机预测相反，在Ames试验(平板掺入法)中，无论是否有S9代谢激活，这两种化学物质都没有致突变性。

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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.