ACC’s Hexavalent Chromium Panel: Statement on EPA’s Final IRIS Toxicological Review of Hexavalent Chromium

WASHINGTON (August 29, 2024) - Today, the American Chemistry Council's (ACC) Hexavalent Chromium panel issued the following statement on the release of the Environmental Protection Agency's (EPA) Final IRIS Toxicological Review of Hexavalent Chromium:

"EPA's final IRIS Toxicological Review of Hexavalent Chromium (Cr(VI)) reflects an abrupt shift in the basis of EPA's oral cancer slope factor (CSF) from intestinal cancer in mice (2022 draft) to oral mucosa cancer in rats without any external peer review of this endpoint as the primary driver for EPA's conclusion.

"We also are extremely disappointed that EPA continues to assert that Cr(VI) operates via a mutagenic mode of action (MOA) for the oral route of exposure. This conclusion is counter to the weight of the evidence and is in stark contrast to the conclusions of other regulatory and scientific authorities which have reviewed the same available data.

"EPA's draft IRIS Toxicological Review (2022) proposed an oral CSF based on intestinal tumors in mice. An EPA SAB panel in 2023 asked the EPA IRIS Program to re-evaluate the carcinogenicity of Cr(VI) in the low dose region, believing that there are nonlinearities in the kinetics of Cr(VI) that would limit carcinogenicity at low exposures, and that EPA's draft approach overestimated risk.

"After reviewing the SAB recommendations, EPA determined that the oral tumors in rats posed greater risk and abruptly changed the basis of its oral CSF from intestinal cancer in mice (2022 draft) to oral mucosa cancer in rats in the final Toxicological Review. The SAB, therefore, has not had the opportunity to thoroughly review EPA's new CSF. Additionally, it is unclear whether the revised assessment addresses the SAB's concerns about the low dose carcinogenicity of Cr(VI).

"No other regulatory or scientific authorities have derived toxicity criteria based on oral cavity tumors in rats (tumors that were significantly elevated only at 180 ppm Cr(VI)). Other agencies have concluded that protecting against the non-cancer effects in the small intestine protects against intestinal cancer as well as oral cancer. These conclusions are based on empirical studies demonstrating that Cr(VI) does not cause genotoxicity in the intestine or oral mucosa - indicating a non-mutagenic MOA. Peer-reviewed research has previously shown that 180 ppm Cr(VI) does not increase mutations in the oral cavity of transgenic Big Blue^® TgF344 rats (Thompson et al., 2015). Additionally, research demonstrated that exposure of up to 180 ppm Cr(VI) did not result in any gene expression changes in the oral mucosa of rats or mice, suggesting no cellular response to Cr(VI) in the mouth (Thompson et al. 2016).

"In a published article in 2018, it was demonstrated that the margin of exposure (MOE) for the oral tumors was greater than 30,000, indicating low risk to humans and as such, risk assessments should focus on other effects caused by Cr(VI).

• Using the EPA (2022, 2024) BMDL10 for oral tumors (2.7 mg/kg-day) and the Health Canada (2016) estimated adult daily exposure to Cr6 (0.000065 mg/kg-day) results in an MOE >41,000 (2.7 / 0.000065).

"EPA continues to demonstrate a disregard for well-conducted mechanistic research supporting a non-mutagenic MOA. Other international regulatory and scientific authorities, including Health Canada (2016), the World Health Organization (2020), and the Food Safety Commission of Japan (2019), have reviewed the same data available to EPA and concluded that the weight of evidence points to the occurrence of a threshold MOA for Cr(VI) carcinogenesis for the oral route of exposure.

"Over 30 peer-reviewed scientific publications provide support that the current EPA drinking water standard - also known as maximum contaminant level (MCL) - for total chromium continues to be health protective for all forms of chromium in drinking water. EPA's approach and results could lead to values far lower than the average background levels of hexavalent chromium in groundwater and could lead to future regulatory action that would impose massive costs to water systems nationwide with little to no public health benefit.

"We look forward to engaging with EPA as it carefully works through the Safe Drinking Water Act process in considering whether to change the current MCL for total chromium, assessing technical and economic feasibility, and costs and benefits including health effects associated with an alternative MCL."

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