Dr. Csaba Boglári, Ph.D. is a Molecular Biologist by training. He obtained his Ph.D. in Molecular Neuroscience from the University of Basel in 2020. In 2022, he contributed to public health efforts, managing vaccine operations as Supervisor of Vaccine Management at the Vaccination Center in Basel, Switzerland. Transitioning into industry roles, he joined Edelweiss Connect in Basel, Switzerland, as a Customer Innovation Manager in 2022. Since 2023, he serves as the Scientific Director at Xenometrix AG in Allschwil, Switzerland, where he has been involved with research and development, quality control, technical support, and the management of international collaboration projects with a strong commitment to bridging scientific research, innovation and customer-centered solutions.
Characterization of the mutagenicity of selected nitrosamines using miniaturized Ames tests
Csaba Boglàri*, Cécile Koelbert *
* Xenometrix AG, Gewerbestrasse 25, Allschwil, Switzerland
Background & Objective | The presence of genotoxic impurities in pharmaceuticals and packaging materials poses a significant health risk, highlighting the need for reliable testing methods to ensure product safety. Growing concerns over nitrosamines have led to a coordinated international effort to develop and refine methods that can effectively assess this class of chemicals. Regulatory bodies, including the EMA and FDA, recommend the Enhanced Ames Test conditions to evaluate the genotoxic potential of nitrosamines, utilizing high concentrations (30%) of liver microsomal fractions to bioactivate these compounds. While current studies primarily use the Agar Plate test to evaluate nitrosamine-related genotoxicity, miniaturized versions of the traditional Ames test could provide robust sensitivity while significantly reducing the amounts of test samples, S9 microsomal fractions, and plasticware needed.
Methods | Our approach includes two miniaturized versions of the Ames assay: the agar-based MicroAmes6 in a 6-well plate format and the liquid microplate fluctuation assay known as Ames MPF, utilizing the three strains TA100, TA1535, and E. coli uvrA[pKM101]. We have modified the original protocols to test short alkyl chain nitrosamines.
Results & Discussion | We conclude that miniaturized Ames tests present a resource-efficient solution for assessing the mutagenicity of nitrosamines. Therefore, we strongly advocate for the widespread adoption of these miniaturized assay formats across various industries.
Keywords
Nitrosamines, Genotoxic impurities, Genetic Toxicology, Mutagenicity, Miniaturized Ames assays, Ames MPF, Ames microfluctuation test, Ames test in 6-well agar plate format, NAMs, 3Rs
