More than you wanted to know about chromate induced cancer

Chromium is OK when it's on your car bumper but not so OK when it's in your workplace air or your drinking water. That's because chromium, in some of its forms, causes cancer. In fact it is a remarkably good carcinogen. A few years, ago both epidemiological studies and risk estimates done by the US Environmental Protection Agency (EPA) suggested the lifetime risk of dying of lung cancer for workers exposed at the then workplace limits as about 25%. This is higher than for heavy cigarette smokers. The US Occupational Safety and Health Administration (OSHA) lowered the workplace standard by a factor of ten in 2006, but even at that level the risk is estimated at 10 - 45 excess lung cancers per thousand workers. And there are a lot of chromate exposed workers -- 360,000 in the US and millions worldwide. And it's not just workers. Many hazardous waste sites contain chromates that contaminate nearby air or drinking water supplies. The famous Erin Brockovitch case involved environmental chromate contamination.

Chromate occurs in several chemical forms, distinguished by their oxidation states. There is Chromate(VI), Chromate(V), Chromate(IV) and Chromate(III). The kind that poisons people is Chromate(VI), hexavalent chromium, although interestingly, hexavalent chromium is not itself carcinogenic. Its claim to fame is its ability to get into the cell, at which time it is successively converted to lower oxidation, ending with the carcinogenic Chromate(III). Chromate(VI) is like the murderer who gains access wearing an innocent mask and once inside rips his mask it off to reveal the villain beneath. This much has been known for some time, but there remain a number of mysteries about Chromate. One is that when studied in tissue culture it is not a very potent source of mutations. Since chromate's carcinogenic potential is thought to be related to its ability to cause mutations in cells, its failure to do this except at very high doses has led some to say that Chromium isn't the bad actor it was thought to be, except at very high levels.

In recent years, though, we have been learning new and surprising things about chromate toxicity and some of it implicates a common over-the-counter diet supplement, ascorbic acid (Vitamin C). Work done by Anatoly Zhitkovich and his colleagues and students at Brown University has revealed that chromate carcinogenicity depends on the failure of a repair system for DNA damage, the kind called DNA mismatch repair. Here is the provisional picture as assembled by that group. Ascorbate is a strong potentiator of chromate metabolism from the VI form to the III form. Tissue cultures have low ascorbate levels so that transformation occurs more slowly in that experimental system. But when there is adequate ascorbate the chromate is much more toxic and triggers the operation of the DNA mismatch repair system. This system either repairs the damage, or if the damage is too serious to repair, causes the cell to die. This is protective. You don't want defective cells to keep growing since some of them might grow in uncontrolled ways, i.e., become cancerous. But what the Brown group suggests is that under the pressure of repair proficient cells killing themselves, there is an opening for the occasional aberrant mismatch repair deficient cells to thrive. The escape from repair allows the emergence of clones that are both resistant to the toxic effects of chromates and genetically defective and some of them are damaged in ways that allow them to grow wild, i.e., as cancers.

So paradoxically, the "eat your fruits and vegetables" mantra is working against the chromate worker or resident of a chromate contaminated neighborhood. The Vitamin C (ascorbate) in the fruits is jacking up chromate cellular toxicity. As I said, paradoxical. And damn interesting.

Some papers from the Brown University group here, here, here and here.

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This past science fair season, my daughter wanted to do a project involving crystals. She has one of those science-projects-for-kids books that suggested a number of different compounds for making crystals of different colors, and one of the choices was potassium chromate. After I ordered the chemicals, we read through the label info and decided that there was no way we wanted to mess with the stuff. I went back and checked the copyright on the book after that. It was published in 1992, which I wouldn't have thought was all that long ago.

Now I need to see if I can find some local school to take the stuff off my hands--it's not returnable, and it can't be discarded either.

Looks like the bottom line is that chromate workers need to choose between scurvy and cancer.

Where's Hobson when you need him?

The physical form of the chrome is very important, and was has a lot to do with toxicity. Worker exposure is mainly to _inhaled, metallic chrome_, and the target tissue is alevoles, umm, you know, the little air sacs. Drinking water is, umm, mainly drunk (yeah, those long hot showers where the chrome gets aerosolized and breathed don't count, because it's still *dissolved* phase), and _dissolved_ chrome in water is not hitting the same tissues, in the same form, as the metal dust in the lung tissue. So of course there will be differences in results, depending on how the in vitro model copies the occupational exposure. Note also that breakfast cereals are _fortified_ with an MDR of chromium, which is in a soluble form, not the free metal. No wonder all the studies are all over the place, half the time they are comparing apples with oranges.

Doesn't this imply that Chromate (VI) exposure should have a bigger effect on older people, since older people expect to have more exposed cells that have mutated so that their DNA repair machinery is not working anymore?

By albatross (not verified) on 29 Feb 2008 #permalink

My. I remember having a chemistry set with a vial of Potassium hexachromate.

By Sock Puppet of… (not verified) on 29 Feb 2008 #permalink

albatross: There are a lot of possibilities but which ones are important, if any, is hard to say. The older you get the less likely you are to be exposed to chromate occupationally and the more likely to get cancer of almost all kinds so it would be pretty hard to untangle.