Is Hexavalent Chromium Carcinogenic via Ingestion? A Weight-of-Evidence Review

Abstract

Hexavalent chromium [Cr(VI)] is recognized as a human carcinogen via inhalation, based on elevated rates of lung cancer among occupationally exposed workers in certain industries. Cr(VI) is also genotoxic in bacterial and mammalian cell lines. In contrast, scientific panels in the United States and abroad have reviewed the weight of evidence (WOE) and decided that the available data are insufficient to conclude that Cr(VI) is an oral carcinogen. A criterion of 0.2 ppb was established by a California agency for Cr(VI) in drinking water to prevent cancer, however, this criterion was withdrawn in November, 2001. This criterion was remarkably lower than the promulgated California and federal drinking-water standards for total chromium of 50 ppb and 100 ppb, respectively. Both of the promulgated standards are designed to be protective of humans who ingest Cr(VI). This article describes a WOE analysis to examine the likelihood that Cr(VI) in drinking water poses a cancer hazard at the current U.S. drinking-water standard. The results indicate that: (1) From the historical epidemiological studies, there are a few reports of increased rates of digestive system cancer among Cr(VI)-exposed workers, although most are not statistically significant; (2) the preponderance of evidence from recent epidemiological studies of Cr(VI)-exposed workers does not support an increased risk of cancer outside of the respiratory system; (3) studies of four environmentally exposed populations are negative; (4) there is only one lifetime animal feeding study, and the findings from that study are considered to be flawed and inconclusive; and (5) recent kinetics and in vivo genotoxicity data demonstrate that Cr(VI) is reduced to nontoxic Cr(III) in saliva, in the acidic conditions of the stomach, and in blood. In short, at concentrations at least as high as the current U.S. maximum contaminant level (100 ppb), and probably at least an order of magnitude higher, Cr(VI) is reduced to Cr(III) prior to or upon systemic absorption. The weight of scientific evidence supports that Cr(VI) is not carcinogenic in humans via the oral route of exposure at permissible drinking-water concentrations.

Cancer after Total Joint Arthroplasty: A Meta-analysis

“…Chromium, which is found in some metallic implants, has been shown to induce prostatic tumors in rats (34), but this association has not been clearly seen in epidemiologic studies (35)(36)(37)(38)(39). Latency for metalassociated cancers is typically long, at least for occupational exposures (40), so the fact that an increased prostate cancer risk was seen within the first 5 years after the procedure suggests that the excess risk is probably not due to the prosthesis.…”

Trivalent and Hexavalent Chromium Issues in Medical Implants

“…Despite it's genotoxicity, Cr +6 has not been shown to cause cancer upon oral or dermal exposure in animals or humans or outside the respiratory system [1]. Detoxification by relatively rapid reduction of Cr +6 to the trivalent state in most biological systems and conditions is believed to be the primary reason why Cr +6 does not pose a cancer hazard outside of the lung [33,34].…”

Environmental Pollution Effects on Mortality in an Industrial and a Non-industrial Municipality, in Voiotia Prefecture, Greece

“…Furthermore, although Cr(VI) has been long recognized as a human carcinogen through inhalation (International Agency for Research on Cancer [IARC], 1990), there is still significant debate on the carcinogenicity of Cr(VI) when it is orally ingested. Cr(VI) at the cellular level is a highly active carcinogen (Costa, 1997;Proctor et al, 2002). It is not clear, though, whether Cr(VI) ingested through the oral route, converts to trivalent chromium Cr(III) (which does not easily cross the cell membrane) before entering a living cell (Costa, 2003).…”