Gait kinematics and kinetics in patients with chronic ankle instability and healthy controls: A statistical parametric mapping analysis.

Background: Chronic ankle instability (CAI) is associated with changes in gait biomechanics which may be related to chronic dysfunction. Traditional statistical models may be limited in their ability to assess the complex 3D movement of the lower extremity during gait. Multivariate analysis of the lower extremity kinematics may reveal unique biomechanical differences associated with CAI.

Mechanisms of Nitrosamine Mutagenicity and Their Relationship to Rodent Carcinogenic Potency.

A thorough literature review was undertaken to understand how the pathways of -nitrosamine transformation relate to mutagenic potential and carcinogenic potency in rodents. Empirical and computational evidence indicates that a common radical intermediate is created by CYP-mediated hydrogen abstraction at the α-carbon; it is responsible for both activation, leading to the formation of DNA-reactive diazonium species, and deactivation by denitrosation. There are competing sites of CYP metabolism (e.

Principles and Procedures for Assessment of Acute Toxicity Incorporating Methods.

Acute models are being used to support an increasing number of application areas including (1) product research and development, (2) product approval and registration as well as (3) the transport, storage and handling of chemicals. The adoption of such models is being hindered, in part, because of a lack of guidance describing how to perform and document an analysis. To address this issue, a framework for an acute toxicity hazard assessment is proposed.

Use of the bacterial reverse mutation assay to predict carcinogenicity of N-nitrosamines.

Under ICH M7, impurities are assessed using the bacterial reverse mutation assay (i.e., Ames test) when predicted positive using in silico methodologies followed by expert review.

Utility of a next-generation framework for assessment of genomic damage: A case study using the pharmaceutical drug candidate etoposide.

We present a hypothetical case study to examine the use of a next-generation framework developed by the Genetic Toxicology Technical Committee of the Health and Environmental Sciences Institute for assessing the potential risk of genetic damage from a pharmaceutical perspective. We used etoposide, a genotoxic carcinogen, as a representative pharmaceutical for the purposes of this case study. Using the framework as guidance, we formulated a hypothetical scenario for the use of etoposide to illustrate the application of the framework to pharmaceuticals.