GLR Laboratories (Europe) Pvt Ltd, Sharnbrook, MK44 1LZ, United Kingdom; GLR Laboratories Pvt Ltd, Chennai, 600068, India.
Department of Fiber Science & Apparel Design, College of Human Ecology, Cornell University, Ithaca, NY, 14853, USA.
Toxicol Lett. 2021 May 1;341:59-67. doi: 10.1016/j.toxlet.2021.01.024. Epub 2021 Feb 3.
Toxicological risk assessment of medical devices requires genotoxicity assessment as per ISO 10993, Part 3, which is designed to address gene mutations, clastogenicity and/or aneugenicity endpoints. 'Site of contact genotoxicity' is a potential genotoxic risk especially for medical implants, that is currently not addressed in biocompatibility standards. We therefore performed initial validation study on the use of alkaline single cell gel electrophoresis (comet assay) for detecting 'site of contact genotoxicity' of medical devices, using test items made of acrylic implants impregnated with ethyl methanesulphonate (EMS). Comet assay detected increased DNA migration at the site of implantation, but not in the liver. The same implants also failed to show any genotoxicity potentials, when tested on the standard test battery using Salmonella/microsome and chromosome aberration assays. The study suggested that some medical implants can cause 'site of contact genotoxicity', without producing systemic genotoxicity. In conclusion, comet assay will add new dimension to safety assessment of medical devices, and this assay can be added to the battery of genetic toxicology tests for evaluating biocompatibility of medical implants.
医疗器械的毒理学风险评估需要按照 ISO 10993 第 3 部分进行遗传毒性评估，该部分旨在解决基因突变、断裂剂和/或非整倍性终点。“接触部位遗传毒性”是一种潜在的遗传毒性风险，特别是对于医用植入物，目前在生物相容性标准中并未涉及。因此，我们使用碱性单细胞凝胶电泳（彗星试验）对浸有乙基甲磺酸（EMS）的丙烯酸植入物制成的测试物品进行了初步验证研究，以检测医疗器械的“接触部位遗传毒性”。彗星试验检测到植入部位的 DNA 迁移增加，但在肝脏中没有检测到。当使用沙门氏菌/微粒体和染色体畸变试验的标准测试组合对相同的植入物进行测试时，它们也没有显示出任何遗传毒性潜力。该研究表明，一些医用植入物可能会引起“接触部位遗传毒性”，而不会产生全身遗传毒性。总之，彗星试验将为医疗器械的安全性评估增添新的维度，该试验可以添加到遗传毒性测试组合中，以评估医用植入物的生物相容性。
