The overall aim of the proposed project is to provide a systematic and quantifiable comparison of NOAELs derived from animal studies with those from human studies for a range of chemicals and to develop robust evidence synthesis (meta-analytical) methodology combining all available information for derivation of an integrated NOAEL. Specific objectives include:
Identification and listing of chemical agents for which substantial animal and human data are available.
- Description of available animal and human data including study design, size, route and form of exposure and health endpoints; Quality of the information and suitability for derivation of NOAELs will be evaluated;
- For substances with good quality data, categorised by class of substance and health endpoint, comparison of the NOAELs derived from human data and animal data in relation to the nature and quality of the data, the derivation methods and the relevance to the most common human route and form of exposure; investigation of factors affecting relationship between animal and human NOAELS, using regression modelling and other methods:
- Building on available cross-design evidence synthesis methods, development of meta-analysis techniques for combining human and animal data to derive dose-response curves (and thresholds if they exist). Application to selected examples; comparison of added value of combining animal and human data with use of either alone.
- Development of recommendations for evaluation of future substances and for design of future studies.
Animal NOAELS: does adding human data help? by Lesley Rushton, Alan Boobis, David R Jones, Karin Burnett, Kate Vassaux, presented at the 14th Cefic-LRI Annual Workshop 2012
Reference doses: animal or human data...or both?, by David R Jones, presented at the 16th Cefic-LRI Annual Workshop 2014