Design and interpretation of rat liver UDS assays

The study design and interpretation criteria for the rat liver UDS assay have evolved over recent years. A database from a single laboratory is presented to demonstrate the range of responses encountered whilst screening 71 industrial and agrochemical compounds for potential genotoxicity, a total of 280 experiments. With a large data set it was possible to delineate clearly the normal responses of the system and apply robust criteria for the evaluation of potentially positive compounds. The rat liver UDS assay proved to be a reproducible, reliable and sensitive technique for the evaluation of genotoxicity in vivo. Experiments with negative control values of (N-C) greater than zero would have been rejected, however the highest negative control value observed was (N-C) = -1.1. Evaluation of data using the current United Kingdom Environmental Mutagen Society (UKEMS) recommended procedures resolved 96% of studies by simple inspection. In the remainder of studies data were clarified by additional experiments under modified conditions. It is unlikely that outcomes would have been improved upon by direct statistical analysis which would require an expanded experimental design. These data confirm the utility of the pragmatic approach of the current UKEMS guidelines.