Classifying Impact Loading Using Axial Peak Tibial Acceleration and Impact-Related Biomechanical Differences During Treadmill Running.

Measuring lower extremity impact acceleration is a common strategy to identify runners with increased injury risk. However, existing axial peak tibial acceleration (PTA) thresholds for determining high-impact runners typically rely on small samples or fixed running speeds. This study aimed to describe the distribution of axial PTA among runners at their preferred running speed, determine an appropriate adjustment for investigating impact magnitude at different speeds, and compare biomechanics between runners classified by impact magnitude.

Critical comparison of BMD and TD methods for the calculation of acceptable intakes for N-nitroso compounds.

The tumorigenic dose 50 (TD) is a widely used measure of carcinogenic potency which has historically been used to determine acceptable intake limits for carcinogenic compounds. Although broadly used, the TD model was not designed to account for important biological factors such as DNA repair and cell compensatory mechanisms, changes in absorption, etc., leading to the development of benchmark dose (BMD) approaches, which use more flexible dose-response models that are better able to account for these processes.

Resolution of Historically Discordant Ames Test Negative / Rodent Carcinogenicity Positive N-nitrosamines using a Sensitive, OECD-aligned Design.

The in vitro Bacterial Reverse Mutation (Ames) Test is crucial for evaluating the mutagenicity of pharmaceutical impurities. For N-nitrosamines (NAs) historical data indicated that for certain members of this chemical class the outcomes of the Ames Test did not correlate with their associated rodent carcinogenicity outcomes. This has resulted in negative outcomes in an OECD aligned Ames Test alone (standard or enhanced) no longer being considered sufficient by regulatory authorities to assess potential carcinogenic risk of NAs if present as impurities in drug products.