This is an important study for chromium 6 risk assessment. Humans exhibit a relatively high capacity for Cr6 reduction to Cr3 in the stomach prior to intestinal absorption. This is an important detoxification mechanism for Cr6.
Sasso AF, Schlosser PM. An evaluation of in vivo models for toxicokinetics of hexavalent chromium in the stomach. Toxicology and applied pharmacology. 2015 Jun 27. pii: S0041-008X(15)30023-5. doi: 10.1016/j.taap.2015.06.016.
Hexavalent chromium (Cr6) is a drinking water contaminant that has been detected in most of the water systems throughout the United States. In 2-year drinking water bioassays, the National Toxicology Program (NTP) found clear evidence of carcinogenic activity in male and female rats and mice. Because reduction of Cr6 to trivalent chromium (Cr3) is an important detoxifying step in the gastrointestinal (GI) tract prior to systemic absorption, models have been developed to estimate the extent of reduction in humans and animals. The objective of this work was to use a revised model of ex vivo Cr6 reduction kinetics in gastric juice to analyze the potential reduction kinetics under in vivo conditions for mice, rats and humans. A published physiologically-based pharmacokinetic (PBPK) model was adapted to incorporate the new reduction model. This paper focuses on the toxicokinetics of Cr6 in the stomach compartment, where most of the extracellular Cr6 reduction is believed to occur in humans. Within the range of doses administered by the NTP bioassays, neither the original nor revised models predict saturation of stomach reducing capacity to occur in vivo if applying default parameters. However, both models still indicate that mice exhibit the lowest extent of reduction in the stomach, meaning that a higher percentage of the Cr6 dose may escape stomach reduction in that species. Similarly, both models predict that humans exhibit the highest extent of reduction at low doses.
Chad M. Thompson, Christopher R. Kirman, Deborah M. Proctor, Laurie C. Haws, Mina Suh, Sean M. Hays, J. Gregory Hixon and Mark A. Harris. A chronic oral reference dose for hexavalent chromium-induced intestinal cancer. Journal of Applied Toxicology, DOI: 10.1002/jat.2907
High concentrations of hexavalent chromium [Cr(VI)] in drinking water induce villous cytotoxicity and compensatory crypt hyperplasia in the small intestines of mice (but not rats). Lifetime exposure to such cytotoxic concentrations increases intestinal neoplasms in mice, suggesting that the mode of action for Cr(VI)-induced intestinal tumors involves chronic wounding and compensatory cell proliferation of the intestine. Therefore, we developed a chronic oral reference dose (RfD) designed to be protective of intestinal damage and thus intestinal cancer. A physiologically based pharmacokinetic model for chromium in mice was used to estimate the amount of Cr(VI) entering each intestinal tissue section (duodenum, jejunum and ileum) from the lumen per day (normalized to intestinal tissue weight). These internal dose metrics, together with corresponding incidences for diffuse hyperplasia, were used to derive points of departure using benchmark dose modeling and constrained nonlinear regression. Both modeling techniques resulted in similar points of departure, which were subsequently converted to human equivalent doses using a human physiologically based pharmacokinetic model. Applying appropriate uncertainty factors, an RfD of 0.006 mg kg–1 day–1 was derived for diffuse hyperplasia—an effect that precedes tumor formation. This RfD is protective of both noncancer and cancer effects in the small intestine and corresponds to a safe drinking water equivalent level of 210 µg l–1. This concentration is higher than the current federal maximum contaminant level for total Cr (100 µg l–1) and well above levels of Cr(VI) in US drinking water supplies (typically ≤ 5 µg l–1).
Click here for full paper (fee).
In classic fashion, the State of California has ignored the best available science in setting an MCL for hexavalent chromium. The 10 ppb level has little justification (other than someone’s whimsical thinking) considering that public health goals are based on multiple precautionary assumptions with little relevance to human health and recent studies are not considered.
Look for the Natural Resources Defense Council (NRDC), itself an oxymoron, and the Environmental Working Group to file a lawsuit. Historically, their interest is in using government to further their ideology. In the past drinking water has been a convenient litigation lever for them and I would not expect this to change now.
A public meeting is scheduled for June 25-27, 2014 to discuss the following scientific issues related to hexavalent chromium. Click here for more information.
- Cancer classification by inhalation.
- Noncancer hazards to be considered.
- Susceptibility of mice to gastrointestinal toxicity.
- Utility of subchronic histopathological data.
- Database for reproductive and developmental effects.
- Relation between anemia and oral tumors in rats.
CDPH Submits Final Regulation Package Regarding Hexavalent Chromium (Cr VI) and Drinking Water
Contact: Anita Gore, Heather Bourbeau (916) 440-7259
The California Department of Public Health (CDPH) today submitted to the Office of Administrative Law (OAL) its final proposed regulation establishing the first ever drinking water Maximum Contaminant Level (MCL) for hexavalent chromium (Cr VI). More than 18,000 comments were received by CDPH regarding the proposed regulation. The proposed final regulation documents include the Summary and Response to comments received.
The proposed final regulation will take effect after it has been reviewed and approved by OAL in compliance with the Administrative Procedures Act. This review can take up to 30 working days to complete. Once approved, the regulation is then filed with the Secretary of State and will become effective the first day of the following quarter.
“The drinking water standard for hexavalent chromium of 10 parts per billion will protect public health while taking into consideration economic and technical feasibility as required by law,” said Dr. Ron Chapman, CDPH director and state health officer.
If the regulation is approved as expected, implementation of the new drinking water standard for hexavalent chromium will begin July 1, 2014.
Today’s filing also complies with timelines imposed by the Alameda Superior Court in Natural Resources Defense Council, Inc. v. California Department of Public Health.
The department’s response to comments and regulations submitted can be found on the CDPH website.
The lawsuit filed against the state of California was done for one purpose — get press coverage to make a political impact and raise funding support (click here)…..I’ve seen this too many times to be fooled into thinking it is about health.
The Natural Resources Defense Council has been using this tactic for many years….it is primary funding source…..it allows them to put pressure on government, to claim (falsely) that republicans want dirty water and dirty air. When NRDC’s other environmmental agenda items stall, they always pivot to water….who could be against safe drinking water? Nobody. So it looks like they are doing something good….when in fact, the action is simply a ploy….
Posted in Cr-VI
The Natural Resources Defense Council and the Environmental Working Group filed the lawsuit today, claiming the department is eight years late in setting the hexavalent chromium standard and has made no progress toward the goal.
This type of lawsuit is standard practice for environmental groups that are interested in fund raising, not the public….Click here for news article…