Genotoxicity Assessment of Ultra-High Molecular Weight Polyethylene (UHMWPE) using Bacterial Reverse Mutation and In vitro Chromosomal Aberration Assays

Objectives: Ultra High Molecular Weight Polyethylene (UHMWPE) is extensively used in orthopedic and implantable medical devices, yet data on its genotoxic potential remain limited. This study aimed to comprehensively assess the mutagenic, clastogenic, and aneugenic potential of UHMWPE extracts using two standard in vitro assays. Methods: Following ISO 10993 and OECD guidelines (471 and 473), UHMWPE extracts were prepared using polar and non-polar solvents. Mutagenicity was evaluated using Salmonella typhimurium strains (TA98, TA100, TA102, TA1535, and TA1537) with and without S9 metabolic activation. In vitro Chromosomal aberration analysis was performed on cultured human peripheral blood lymphocytes exposed to UHMWPE extracts at 25%, 50%, and 100% concentrations under both short-term (±S9) and longterm (-S9) exposure conditions. Findings: In the Ames test, no significant increase in revertant colonies was observed across strains, indicating no mutagenic activity. Revertant counts for the test material ranged from 125 ± 6 to 130 ± 6 CFU/plate, similar to negative controls (e.g., TA100: 126 ± 6 vs. 136 ± 13). In contrast, positive controls like mitomycin C showed marked increases (e.g., TA102: 703 ± 35; TA1537: 351 ± 15), confirming assay validity. In the chromosomal aberration assay, the test material induced no significant structural or numerical aberrations, with aberrant cells at 1%–4% (vs. 14%–22% for positives). The mitotic index remained within normal range (8.5 with S9; 8.8 and 7.6 without S9), and numerical aberrations stayed below 1%, unlike positive controls (up to 5.7%). Novelty: This study uniquely evaluated UHMWPE extractables (not wear particles) for genotoxicity using both assays under internationally accepted regulatory protocols. It provides new safety evidence supporting the non – mutagenic and non – clastogenic nature of UHMWPE in medical device applications. Keywords: UHMWPE; Genotoxicity; Ames Test; Chromosomal Aberration; Medical Devices; Biocompatibility