Effects of MTBE on Leydig cell tumors in Sprague-Dawley rats: Range of possible Poly-3 results

An increased Leydig cell tumor (LCT) incidence was reported in a study of Sprague-Dawley (SD) rats exposed to 1000 (but not 250) mg/kg-day MTBE via gavage; however, its unclear if this finding was due to the statistical analyses not adequately accounting for the increased survival rate in the high-dose animals and/or for multiple statistical comparisons. While the study reported some overall survival data, it did not specify which rats had LCTs. We conducted separate Poly-3 analyses for the most extreme scenarios of survival age and tumor incidence because the true data fall somewhere within this range. We used p-values of 0.01 for pair-wise comparisons and 0.005 for trend tests of common tumors as recommended to control for the overall false-positive error rate that can arise from multiple comparisons of tumor incidences in the large number of tissue/organ sites examined in chronic bioassays. We found that MTBE does not cause a statistically significant increase in LCTs in SD rats when survival is appropriately taken into account. Thus, these data do not support a causal association between MTBE exposure and LCTs.