Developing adjustment factors to estimate the combined cancer risk of trichlorethylene

Introduction The Integrated Risk Information System (IRIS) assessment for trichloroethylene (TCE) found that human data were sufficient to support dose-response modeling and to develop an inhalation unit risk (IUR) for renal cell carcinoma (RCC). However, human and rodent data suggest that TCE exposure also increases the risk of non-Hodgkin’s lymphoma (NHL) and liver cancer. A combination of two different approaches was used to adjust the IUR to account for potential increased risk of these additional cancer types. Methods A factor was developed and applied to the IUR to obtain a combined unit risk estimate (i.e., lifetime extra risk for developing any of the three types of cancer). The adjustment factor to account for the relative contributions to extra risk was calculated from two different data sets: meta-analyses of human epidemiologic data for the three cancer types, and a large cohort study with relative risk (RR) estimates for all three cancer types. Results The factor developed accounted for the relative contributions of the three cancer types combined in contrast to the extra risk for RCC alone. The calculations based on two different data sets yielded comparable values for the adjustment factor (both within 25% of the selected factor of 4). Conclusion Relative contributions to extra risk were estimated in the absence of dose-response data by calculating an adjustment factor for the additional risk of NHL and liver cancer, in addition to RCC alone. The use of two data sets analyzed by different methods provided more robust support for the use of the factor of 4, based on high-quality epidemiological data.

Impact/Purpose

This poster provides an example of how triangulation, the process of integrating results from different approaches and recognizing that each approach may have different, unrelated sources of potential bias, has been used in chemical health assessments. For the Integrated Risk Information System (IRIS) assessment for trichloroethylene (TCE), human data were sufficient to support dose-response modeling and develop an inhalation unit risk (IUR) for renal cell carcinoma, but human and rodent data suggest that TCE exposure also increases the risk of non-Hodgkin’s lymphoma and liver cancer. Triangulation was used to bring together information on the three cancer types through the use of two statistical/study design approaches (i.e. meta-analysis of three studies being one approach, large cohort studying all three outcomes being the other approach). In accepting a cancer IUR that underestimates the known cancer risk (by just using the unit risk we can directly estimate), we bring external (or indirect) knowledge on the relative proportion of the other cancers to the known cancer and estimate an adjustment factor so that the IUR actually estimates the full cancer risk.

Citation

Powers, M., T. Bateson, AND B. Glenn. Developing adjustment factors to estimate the combined cancer risk of trichlorethylene. NASEM Workshops to Support EPA's Development of Human Health Assessments: Triangulation of Evidence in Environmental Epidemiology, N/A, DC, May 09 - 11, 2022.