Initial consideration for use of transgenic mutation assays in a regulatory submission.

As an initial consideration for use of TM assays in a regulatory submission, we focus here especially on the following questions: (1) What conditions would trigger the performance of a TM assay? (2) What data set is sufficient to support a negative result? and (3) What increase in mutation frequency is considered to be a positive result? In the first question, we discuss outcomes from traditional tests such as RM, CA, GM, and MN assays. In the second question, we propose a provisional data set including several items, i.e., experimental size [number of animals per group, number of plaques per animal (tissue)], tissue selection, route of administration, top dose level, number of dosings (single vs. multiple), sampling time, number of samples, dose levels, and positive and negative controls. Some statistical and biological considerations are needed for the third question.