Dose finding in the Ames Salmonella assay

Threshold dose/concentration values, such as the lowest effective dose, min imum effective dose or the lowest effective concentration (LED, MED or LEG, respectively) are in use as an alternative to the mutagen potency measures based on the 'rate' measurements (e.g., the slope of the initial part of t he dose-response curve). In this respect, several statistical procedures fo r the corresponding so-called 'dose finding' were proposed during the last decades. However, most of them disregard the discrete nature of responses s uch as the plate colony count in the Ames Salmonella assay. When the plate counts agree with the Poisson assumption, two procedures considered here se em to be appropriate for the dose finding. One is based on the stepwise col lapsing of the homogeneous control and dose counts; another consists of con structing the confidence limits for the mutation induction factor (MIF). Wh en the dose and control counts are non-overlapping, the simple 'visual' non -parametric estimation of LED is possible. Applicability and validity of th e methods is demonstrated with the two data sets on the mutagenicity of the P-carboline alkaloid, harmine, and one of the oxidation products of apomor phine. (C) 2000 Elsevier Science B.V. All rights reserved.