A Study on the Consistency between Statistical Evaluation and Toxicological Judgment

Abstract

A study was planned which evaluated the consistency between the judgments of toxicologists and well-established statistical methods to detect dose-dependency in repeated toxicity studies. Eighteen bits of repeated toxicity study data for both male and female rats were collected, which included hematology, blood chemistry, and organ weight (absolute and relative) data, totaling 2,001 items. Three or four toxicologists who had more than 10 years of experience judged dose-dependency and change at each dose for each item. The consistency between statistical methods and toxicologists was not as high as was expected. One of the major sources of this inconsistency resulted from the large amount of variation in the recognition among toxicologists. The recognition was qualitatively different, for instance, when there was a difference only between the highest dose and the control group, even if it was very evident, some toxicologists did not regard it as a dose-dependent relationship. It was shown that the consistency of change at each dose was moderately high. It is also noted that toxicologists tend to judge more conservatively than statistical tests at the 5% significance level. Considering the result of this study, a maximum contrast method is recommended to examine the dose-response shape, while avoiding the multiplicity of statistical tests.