Effects of MTBE on the reported incidence of Leydig cell tumors in Sprague-Dawley rats: range of possible Poly-3 results

Abstract

An increased Leydig cell tumor (LCT) incidence has been reported in a study of Sprague-Dawley (SD) rats exposed via gavage to 1000 (but not 250)mg/kgday MTBE; it is unclear, however, if this finding was indeed dose-related or due to the statistical analyses not having adequately accounted for the increased survival rate in the high-dose animals and/or for multiple statistical comparisons. To address this question, we conducted Hoel-Walburg and Poly-3 analyses, using p-values of 0.01 for pair-wise comparisons and 0.005 for trend tests of common tumors. We found that MTBE does not cause a statistically significant increase in LCTs in SD rats when survival is appropriately taken into account. In addition, the original study reported some overall survival data, but did not specify which rats had LCTs. This led us to conduct separate Poly-3 analyses for the most extreme scenarios of survival age and tumor incidence to provide an illustrative example of approaches for analyzing the impact of survival rates on tumor findings in the absence of animal-specific survival data. We found this method to provide results similar to analyses using the actual data, suggesting that it can be used when full survival data are not available.