Comment submitted by Rosalind Schoof, FMC Corporation

The underlying toxicity database for 1,2,3-trichloropropane (1,2,3-TCP) is relatively robust, providing adequate data to support the dose response assessment. The USEPA draft assessment generally applies the available data appropriately and methodologies for the derivation of the toxicity criteria are generally sound; however, we do have several recommendations for revisions. Despite the robustness of the database, USEPA has applied large uncertainty factors (UFs) in the reference dose (RfD) and reference concentration (RfC) assessments. The UF for the RfD is 300, while the UF for the RfC is 3,000. In both cases these UFs are inflated by the application of additional factors to account for limitations in reproductive and developmental studies. Considering that toxic endpoints of questionable toxicological significance are used for both the RfD (i.e., increased absolute liver weight) and the RfC (peribronchial lymphoid hyperplasia), the application of such high UFs does not seem warranted. We recommend that in both cases three-fold lower UFs would be adequately protective for adverse health effects. Thus, we recommend a UF of 100 for the RfD and a UF of 1,000 for the RfC. The cancer assessment yielded an oral cancer slope factor (CSF) based on a National Toxicology Program (NTP) two year gavage study in rats. There are questions about the applicability of gavage data in assessing human exposures via drinking water. La et al. (1996) extracted a greater amount of DNA adduct from liver tissues of animals receiving 1,2,3-TCP via gavage compared to those exposed via drinking water. While cellular proliferation increased with dose in tissues of animals exposed to 1,2,3-TCP by gavage, little change was seen in the tissues of animals exposed to drinking water (La et al. 1996, as cited in USEPA 2007). This finding suggests that bolus dosing of concentrated solutions may be a critical factor in the tumorigenic capacity of 1,2,3-TCP, a factor that could contribute to substantial overestimation of cancer risks in humans exposed via drinking water. This factor should be more thoroughly evaluated by USEPA in the dose response assessment.