STATISTICAL-ANALYSIS OF DOSE-RESPONSE DATA FROM IN-VITRO ASSAYS - AN ILLUSTRATION USING SALMONELLA MUTAGENICITY DATA

One of the advantages of in vitro methods is ease of testing multiple concentrations of chemicals for dose responses. A well defined respons e is used to confirm toxicity, especially for marginal effects, and a significant dose response alone indicates some effect of treatment for further clarification. For sublethal processes (e.g. enzyme induction , organelle damage or mutagenesis), decreases in response can arise at high dose levels that kill cells (cytolethality). This compromises st atistical analysis of dose responses using standard approaches, such a s ranking, which do not allow for omission of cytolethal dose data. An alternative is the recursive, non-parametric S-m (1/2)/Jonckheere-Ter pstra test, where omission of results is permitted. Use of this approa ch is illustrated in conjunction with recommended statistical analyses (Dunnett's 't'-test and Wahrendorf ranking) for non-parametric data f rom Salmonella mutagenicity assays where the problem is frequently enc ountered. It is shown that the recursive test can be used for analysin g non-parametric dose responses from in vitro assays, where decreases in response are seen at high test chemical concentrations. (C) 1997 El sevier Science Ltd.