The specific aims of this research are to assess the operating characteristics of the current carcinogen bioassay in small rodents with respect to determining the presence or absence of carcinogenic effect, to identify and develop alternative designs and statistical analyses related to this goal, and to initiate an investigation of the role of the bioassay in low-dose extrapolation and risk assessment. We propose to accomplish these aims though a combination of data analysis, mathematical development computer simulation, and cellegial interaction over a three year period. The enterprise will require the coordinated efforts of biostatisticians, toxicologist, biochemists and computer programmers, and this interaction will be promoted through a biweekly seminar. Our research will proceed with two major foci and four support components. The first focus is the current study of current bioassay with respect to its operating characteristics and development of statistical design and analysis alternatives. The second is to initiate a team approach to the low dose extrapolation, risk assessment problem. These efforts will be supported by the availability of the RED Dye 40 and other data sets, a computer simulation model, a joint statistics/toxicology seminar, and consulting relationships. The results of data analysis will be of interest in themselves and will provide input to the computer simulation system and joint seminar. The simulator will allow design to emulate the current bioassay protocol design and analysis changes we wish to study. It will permit assessment of operating characteristics in situations where too complex for mathematical analysis. The joint seminar will provide the focus for our interaction, with primary focus on the low dose problem. Our ultimate goal is a better understanding of the role of the carcinogen bioassay in small rodents can play in determining carcinogenicity and risk. This better understanding can positively affect the public health both through more credible information when the bioassay is used and the use of other testing means when it is clearly inappropriate.