Calculating excess risk with age-dependent adjustment factors and cumulative doses: ethylene oxide case study

U.S. EPA's Supplemental Guidance in 2005 documented their procedure for incorporating age-dependent adjustment factors (ADAFs) into lifetime excess risk calculations. EPA's first attempt to implement an ADAF when the dose-response model had a cumulative dose metric was for ethylene oxide and that attempt (US EPA, 2006) failed to successfully follow EPA's own guidelines. The failure suggested that the incorporation of ADAFs would increase the lifetime excess risk for ethylene oxide by approximately 66%. However, if the procedure in the guidelines were followed correctly, then the increase would have only been 0.008% or approximately 8,000 fold less. Because cumulative exposure is a common dose metric in dose-response models of epidemiological data, a correct implementation of the guidelines is of widespread importance.