In 2008, NTP reported that very high levels of Cr(VI) in drinking water caused small intestine tumors in laboratory rodents at extremely high concentrations of Cr(VI) (equivalent to 60,000 and 180,000 ppb).
However, because of the study design, NTP could not examine the mode of action (MOA), meaning how the chemical can cause cancer at the cellular level of an organism. It could not predict how the tumors occurred, how to extrapolate these high dose observations to lower, naturally occurring levels in drinking water, or whether these high dose findings are of biological relevance to humans. To put the high NTP doses into perspective, the ATSDR notes that typical US drinking water supplies contain total chromium levels within a range of 0.2 – 35 ug/L with most supplies in the US containing less than 5 ug/L [5 ppb] of chromium.
Because the NTP study did not examine mode of action, which is important for scientists and regulators to understand when evaluating risk, the Hexavalent Chromium Panel (the Panel) of the American Chemistry Council (ACC) agreed to sponsor extensive studies that investigated not only which levels of hexavalent chromium in drinking water can result in adverse effects like cancer, but also how hexavalent chromium can cause cancer in rodents. The studies also developed data describing the differences between rodents and humans in their ability to process and detoxify hexavalent chromium.
The Cr(VI) MOA Study was designed to:
1) better understand how Cr(VI) causes cancer in rodents (e.g., mutagenic or non-mutagenic mode of action) and 2) provide data and analyses to assist regulators in setting drinking water standards for Cr(VI). The studies were designed to mimic NTP conditions, and used mice and rats of the same strains and in similar experimental conditions (same animal feed/cages, same laboratory, same drinking water source) that were used in the 2008 NTP study.
The research led to the publication of over 30 peer-reviewed scientific papers that provide clear data that can help EPA and other regulators confidently set safe drinking water standards for hexavalent chromium. The published MOA research shows:
- There was no observed toxicity in rodents exposed to concentrations of hexavalent chromium in drinking water at the current EPA maximum contaminant level (MCL) of 100 ppb for total chromium. In fact, at hexavalent chromium concentrations ten times the current drinking water exposure limit for total chromium, there was no observed toxicity in the rodents.
- Cr(VI) is not a mutagen (i.e. it has a threshold-based MOA) and drinking water containing less than or equal to 100 ppb total chromium would not be expected to cause cancer in humans.
- In the stomachs of both rodents and humans, Cr(VI) is naturally converted to Cr(III), the non-toxic form of chromium, and at relevant exposures, the conversion occurs more quickly and to a greater extent in humans than rodents. Thus, the science shows the current drinking water standard for total chromium is health protective.