If Cr(VI) is reduced to Cr(III) extracellularly, this form of the metal is not readily transported into cells and so toxicity is not observed. The reduction of Cr(VI) is considered to serve as a detoxification process when it occurs at a distance from the target site for toxic or genotoxic effect while reduction of Cr(VI) may serve to activate chromium toxicity if it takes place in or near the cell nucleus of target organs. It can be absorbed by the lung and gastrointestinal tract, and even to a certain extent by intact skin. The moral of the story is that poorly designed or poorly interpreted animal studies do not predict human risk, and movies are not a very good way to educate the public about toxicology.Since Cr(III) is poorly absorbed by any route, the toxicity of chromium is mainly attributable to the Cr(VI) form. In fact the cancer rates are actually somewhat less than predicted based upon the community population characteristics. There has been long term followup by the State of California in that community and there is no indication of increased risks associated with chromium. This became a hot issue because of the Erin Brokovitch movie from about 15 years ago. ![]() As I said earlier, the more than 30 occupational epidemiology studies do not find cancers other than lung cancers related to inhalation. EPA and California were very premature when they performed risk assessments by misinterpreting the NTP animal test data. 14 mechanistic publications have appeared since then and EPA has not decided how to deal with them. There is also a WHO IPCS document that was out of date when they published it.2 years ago. The EPA document is years out of date and should be ignored where it discusses cancer other than lung cancer from inhalation of CrVI. None of three studies reporting small intestine cancers observed a statistically significant increased risk. Potential confounding by socioeconomic status (SES), diet and/or smoking, or limitations due to the healthy-worker effect (HWE) were evaluated, and while smoking, diet and SES may be important factors that may have upwardly biased the meta-SMRs, HWE is not likely to have significantly affected the summary results. ![]() However, that finding was based on a subgroup of only four studies, one of which was a PMR study. ![]() Analyses of more highly exposed subgroups included in the studies or subgroups based on geographic region or by industry with recognized Cr(VI) exposures (welding, chrome plating, chromate production, and pigment production) did not result in elevated meta-SMRs except for esophageal cancer among US cohorts. Meta-standardized mortality ratios (SMRs) were, for cancer of the: oral cavity esophagus stomach colon and rectum. Based on all the available studies, it has been concluded that there is sufficient evidence in experimental animals for the carcinogenicity of calcium, lead, strontium, and zinc chromates (chromium(VI)) limited evidence for the carcinogenicity of chromium trioxide (chromic acid) and sodium dichromate and inadequate evidence for the carcinogenicity of other chromium(VI) and chromium(IIII) compounds and of metallic chromium. The carcinogenicity of chromium, especially with regard to lung tumours, has also been investigated in a number of inhalation studies in other studies, the chromium was administered by implantation or injection.
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