Utility of Recent Studies to Assess the National Research Council 2001 Estimates of Cancer Risk from Ingested Arsenic

Gibb, Herman J.; Haver, Cary; Gaylor, David W.; Ramasamy, Santhini; Lee, Janice S.; Lobdell, Danelle T.; Wade, Timothy J.; Chen, Chao; White, Paul D.; Sams, Reeder

doi:10.1289/ehp.1002427

Cited by 68 publications

(54 citation statements)

References 35 publications

(118 reference statements)

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“…In addition, the lung and bladder cancer ORs of 2.48 (1.08–5.68) and 2.37 (1.01–5.57), respectively, that we identified in subjects with %MMA in the upper tertile but with arsenic water concentrations <200 μg/L, suggests that arsenic metabolism plays an important role in susceptibility even in people exposed to lower drinking water arsenic concentrations. These latter findings are important since most previous evidence linking ingested arsenic to cancer have involved arsenic water concentrations >200 μg/L (Celik et al 2008; Gibb et al 2011; NRC 1999). Overall, the low p-values, the presence of dose-response relationships, and the consistency with other studies, all suggest that these findings are not due to chance and represent real associations.…”

Section: Discussionmentioning

confidence: 85%

“…Importantly, these risks are estimated based on extrapolations from studies where many people had arsenic water concentrations well above 200 μg/L. As such, the true cancer risks and the impacts of various susceptibility factors at arsenic water concentrations <200 μg/L are mostly unknown (Celik et al 2008; Gibb et al 2011). This is important, since many people in the US and worldwide have arsenic in their water at these lower concentrations.…”

Section: Introductionmentioning

confidence: 99%

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Arsenic methylation and lung and bladder cancer in a case-control study in northern Chile

Melak

Ferreccio

Kalman

et al. 2014

Toxicology and Applied Pharmacology

111

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In humans, ingested inorganic arsenic is metabolized to monomethylarsenic (MMA) then to dimethylarsenic (DMA), although this process is not complete in most people. The trivalent form of MMA is highly toxic in vitro and previous studies have identified associations between the proportion of urinary arsenic as MMA (%MMA) and several arsenic-related diseases. To date, however, relatively little is known about its role in lung cancer, the most common cause of arsenic-related death, or about its impacts on people drinking water with lower arsenic concentrations (e.g., <200 μg/L). In this study, urinary arsenic metabolites were measured in 94 lung and 117 bladder cancer cases and 347 population-based controls from areas in northern Chile with a wide range of drinking water arsenic concentrations. Lung cancer odds ratios adjusted for age, sex, and smoking by increasing tertiles of %MMA were 1.00, 1.91 (95% confidence interval (CI), 0.99–3.67), and 3.26 (1.76–6.04) (p-trend <0.001). Corresponding odds ratios for bladder cancer were 1.00, 1.81 (1.06–3.11), and 2.02 (1.15–3.54) (p-trend <0.001). In analyses confined to subjects only with arsenic water concentrations <200 μg/L (median=60 μg/L), lung and bladder cancer odds ratios for subjects in the upper tertile of %MMA compared to subjects in the lower two tertiles were 2.48 (1.08–5.68) and 2.37 (1.01–5.57), respectively. Overall, these findings provide evidence that inter-individual differences in arsenic metabolism may be an important risk factor for arsenic-related lung cancer, and may play a role in cancer risks among people exposed to relatively low arsenic water concentrations.

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Section: Discussionmentioning

confidence: 85%

Section: Introductionmentioning

confidence: 99%

Arsenic methylation and lung and bladder cancer in a case-control study in northern Chile

Melak

Ferreccio

Kalman

et al. 2014

Toxicology and Applied Pharmacology

111

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“…We were not able to examine risks for exposure to concentrations below 10 µg/L, which is the current US standard. However, because the relative risks are likely to be low (e.g., <1.5), investigating arsenic-cancer relationships at exposures much below 10 µg/L would require incredibly large sample sizes and highly detailed information on confounding (35,36). These issues highlight the importance of investigating moderate exposures (e.g., >10 µg/L) and the likely need for extrapolations when setting standards for arsenic concentrations in drinking water.…”

Section: Discussionmentioning

confidence: 99%

Elevated Lung Cancer in Younger Adults and Low Concentrations of Arsenic in Water

Steinmaus¹,

Ferreccio²,

Yuan³

et al. 2014

American Journal of Epidemiology

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Arsenic concentrations greater than 100 µg/L in drinking water are a known cause of cancer, but the risks associated with lower concentrations are less well understood. The unusual geology and good information on past exposure found in northern Chile are key advantages for investigating the potential long-term effects of arsenic. We performed a case-control study of lung cancer from 2007 to 2010 in areas of northern Chile that had a wide range of arsenic concentrations in drinking water. Previously, we reported evidence of elevated cancer risks at arsenic concentrations greater than 100 µg/L. In the present study, we restricted analyses to the 92 cases and 288 populationbased controls who were exposed to concentrations less than 100 µg/L. After adjustment for age, sex, and smoking behavior, these exposures from 40 or more years ago resulted in odds ratios for lung cancer of 1.00, 1.43 (90% confidence interval: 0.82, 2.52), and 2.01 (90% confidence interval: 1.14, 3.52) for increasing tertiles of arsenic exposure, respectively (P for trend = 0.02). Mean arsenic water concentrations in these tertiles were 6.5, 23.0, and 58.6 µg/L. For subjects younger than 65 years of age, the corresponding odds ratios were 1.00, 1.62 (90% confidence interval: 0.67, 3.90), and 3.41 (90% confidence interval: 1.51, 7.70). Adjustments for occupation, fruit and vegetable intake, and socioeconomic status had little impact on the results. These findings provide new evidence that arsenic water concentrations less than 100 µg/L are associated with higher risks of lung cancer.arsenic; case-control; drinking water; low exposure; lung cancer; northern Chile Abbreviation: CI, confidence interval.High concentrations of arsenic in drinking water (e.g., >100 µg/L) are known to cause cancer, but the risks associated with exposure to lower concentrations are unclear (1-3). One difficulty in studying low-level exposures is the prolonged latency of arsenic-caused cancer (2,(4)(5)(6). This long latency period means that exposure data must be available for a period of several decades or more in order to identify true overall risks. Another difficulty is that exposure in most arsenic-exposed areas comes from thousands of small private wells, for which historic records are frequently unavailable (7).Northern Chile is the driest habitable place on earth. There are few water sources, and almost everyone lives in a city and drinks water from municipal supplies. These supplies have had a wide range of arsenic concentrations, and historical records are available from 40 years ago or more (8). These factors mean that a person's lifetime exposure can be reliably estimated simply by knowing the cities in which the person lived.In 2007-2010, we performed a case-control study in northern Chile and identified high odds ratios for lung, bladder, and kidney cancers (6, 9). These results focused on cities in which arsenic concentrations in drinking water were greater than 800 µg/L. They also involved lifetime average and cumulative exposure metrics, in which short pe...

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“…Another difference is that drinking water exposures are generally much lower than occupational exposures, and this meta-analysis cannot be used to define exact dose–response relationships or low exposure risks. However, owing to the difficulties associated with studying lower exposures in human populations (a greater probability of bias, confounding and insufficient power),6 37 55 chemical risk assessments and regulatory standards are frequently based on higher exposure occupational studies like the ones used here 56. Another consideration is that drinking water exposures may cause greater toxicity because they can take place over the long term (eg, lifetime) and are more likely to occur at particularly susceptible life stages (eg, in fetuses, children and pregnant women) than exposures occurring at work.…”

Section: Discussionmentioning

confidence: 99%

Chromium VI and stomach cancer: a meta-analysis of the current epidemiological evidence

et al. 2014

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Utility of Recent Studies to Assess the National Research Council 2001 Estimates of Cancer Risk from Ingested Arsenic

Cited by 68 publications

References 35 publications

Arsenic methylation and lung and bladder cancer in a case-control study in northern Chile

Arsenic methylation and lung and bladder cancer in a case-control study in northern Chile

Elevated Lung Cancer in Younger Adults and Low Concentrations of Arsenic in Water

Chromium VI and stomach cancer: a meta-analysis of the current epidemiological evidence

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