Statistical model to estimate a threshold dose and its confidence limits for the analysis of sublinear dose–response relationships, exemplified for mutagenicity data

摘要: Abstract Strongly sublinear dose–response relationships (slope increasing with dose) raise the question about a putative threshold dose below which no biologically relevant effect would be expected. A mathematical break in curve at is generally rejected for consequences of genotoxicity such as mutation, because proportionality between low and rate DNA-adduct formation reasonable hypothesis. In view an database distinct deviation from linearity mutagenicity, we offer statistical model to analyze continuous response data estimate together its confidence limits, thereby taking quality degree sublinearity into account. The simplest hockey stick defined by low-dose part slope zero background level theoretical point td , followed linear increase above b . function y (dose d ) =   +   × (  −  ) × 1 [  >  ] Using free statistics software package “R”, make procedure available parameters Confidence intervals are calculated all significance that can user. If lower limit interval >0, rejected. illustrated two examples. small set three replicates per group, indicating induction thymidine kinase mutants L5178Y tk +/− mouse lymphoma cells treated methyl methanesulfonate, did not achieve significance. On other hand, large reported this issue (Gocke et al.) on lacZ bone marrow transgenic mice ethyl methanesulfonate strongly favoured model. theoretically expected dose-related addressed regression estimation upper slope. biological relevance resulting discussed against normal variation measures control group.