Thompson CM, Young RR, Suh M, Dinesdurage HR, Elbekai RH, Harris MA, Rohr AC, Proctor DM. Assessment of the mutagenic potential of cr(VI) in the oral mucosa of big blue® transgenic f344 rats. Environ Mol Mutagen. 2015 May 22. doi: 10.1002/em.21952.
Exposure to high concentrations of hexavalent chromium [Cr(VI)] in drinking water was associated with an increased incidence of oral tumors in F344 rats in a 2-year cancer bioassay conducted by the National Toxicology Program. These tumors primarily occurred at 180 ppm Cr(VI) and appeared to originate from the gingival mucosa surrounding the upper molar teeth. To investigate whether these tumors could have resulted from a mutagenic mode of action (MOA), a transgenic mutation assay based on OECD Test Guideline 488 was conducted in Big Blue® TgF344 rats. The mutagenic oral carcinogen 4-nitroquinoline-1-oxide (4-NQO) served as a positive control. Mutant frequency was measured in the inner gingiva with adjacent palate, and outer gingiva with adjacent buccal tissue. Exposure to 10 ppm 4-NQO in drinking water for 28 days increased mutant frequency in the cII transgene significantly, from 39.1 ± 7.5 × 10-6 to 688 ± 250 × 10-6 in the gingival/buccal region, and from 49.8 ± 17.8 × 10-6 to 1818 ± 362 × 10-6 in the gingival/palate region. Exposure to 180 ppm Cr(VI) in drinking water for 28 days did not significantly increase the mutant frequency in the gingival/buccal (44.4 ± 25.4 × 10-6 ) or the gingival/palate (57.8 ± 9.1 × 10-6 ) regions relative to controls. These data indicate that high (∼180,000 times expected human exposure), tumorigenic concentrations of Cr(VI) did not significantly increase mutations in the gingival epithelium, and suggest that Cr(VI) does not act by a mutagenic MOA in the rat oral cavity.
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.
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…
Mojave Desert ground water contains 14 to 16 ug/L of chromium 6 levels. This exceeds the California public health goal of 0.02 parts per billion. The ultimate state drinking water standard, expected in two to three years, will be higher than the health goal.
But it is very likely that treatmentof ground water owned by Cadiz Inc. will be required before it can be used for drinking water.
Click here for the news article….
To keep the “controversy” alive, expect an article such as this one (click here) every so often. The public health goal (PHG) simply does not represent the safe level of chromium-6 in drinking water…even the State of California acknowledges this. But this is a typical Democrat tactic….keep referring to the PHG to alarm the public. The PHG is a theoretical risk calculation that has little to do with human health.
The maximum contaminant level (MCL) is the safe level…..and there already is an MCL for chromium in California…..
The Safe Drinking Water Act (SDWA) requires the use of the best available peer-reviewed science when establishing drinking water regulations. A peer-review panel recommended inclusion of an inhalation study which is taking additional time. So Rep. Schiff (CA) has introduced a bill to force earlier action……and perhaps reap some political hay.
Click here for news article….