A composite statistical procedure for evaluating genotoxicity using cell transformation assay data

摘要

This study proposes a statistical procedure for evaluating data from the BALB/c 3T3 cell transformation assay (CTA). Three steps are applied: (ⅰ) a Dunnett type test for identifying clear negativity, (ⅱ) a Margolin procedure for detecting and eliminating downturn data, and (ⅲ) a maximum contrast method for evaluating the dose-dependent increase of the response. Using Monte Carlo simulation the proposed procedure was compared to three other methods, i.e.- a linear regression test, the Simpson-Margolin procedure with linear regression test (trend test), and the Omori procedure. When false positive rates were commonly controlled at a similar level for all methods, the procedure's effectiveness was greatest for dose-response patterns exhibiting non-linear and downturn parts, being in agreement with a collaborative CTA validation study performed in Japan. Evaluation of CTA data by the proposed procedure satisfied participating researchers.