Learning Outcomes:

The aims of this module are that the students will be able to understand:

·         All the basic testing methods from Salmonella to whole animal studies

·         In vitro versus in vivo relevance

·         Transgenic models

·         Basis statistical methods

·         General outlines of methods for cancer bioassay and reproductive toxicity

·         Acute and chronic toxicity tests

·         Report writing, key quality criteria for each assay, data interpretation

On the successful completion of the module the students should be able to assess study reports in the context of overall toxicological evaluation. This will require:

·         An understanding and recognition of the mechanisms of interaction of the chemicals with genetic material the DNA

·         An understanding of the mechanisms of repair of DNA damage

·         An appreciation of the relevance of the conversion of DNA lesions into mutations

·         An appreciation of the role of mutations in the induction of cancer

·         An understanding of the contribution of the role of mutations in the production of birth defects

·         The ability to demonstrate the use and ability to  select and apply suitable statistical methods to analyse and critically evaluate genetic toxicology data

·         Critically assess and interpret the data.

Module content:

·         Structure/activity models, their development and application

·         Overview of the methods of chronic and acute toxicity, reproductive toxicity and cancer bioassays

·         Relationships to genetic toxicology tests, their design and application

·         Hazard and risk assessment as illustrated by UK Committee on Carcinogenicity recommendations

·         Transgenic animal mutation models, principles, development, application and interpretation

·         The transition to germ cell studies  Germ cell methods, dominant lethal, heritable translocation, specific locus assay

·         Female methodologies. Embryo analysis

·         Transgenic cancer models – short-term screening, cell transformation models

·         Principles, development and application. Application of mutagenicity testing to the environment, terrestrial and aquatic models – species selection. Development and applications

·         Selection and general application of the new model systems, their integration into testing schemes

·         Introduction to statistical methods in Genetic Toxicology, data analysis and report preparation

·         Mechanistic investigation of a specific compound, interactive workshop.

Pre-course Reading :

·         Parry, J. (2000). Guidance On A Strategy For Testing Of Chemicals For Mutagenicity.

·         Friedberg E.C., Walker , G.C., Siede, W., et al (2006) DNA Repair and Mutagenesis, 2nd edn, pub: ASM Press (ISBN 1-55581-319-4) [core reading for all modules of the MTP]