Critical Aspects of EPA's IRIS Assessment of Inorganic Arsenic Interim Report (2013) / Chapter Skim
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4 Hazard Identification
4 Hazard Identification
Pages 23-50
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From page 23... ...
BOX 5 Concentration Descriptors Used in This Report The terms used here to describe the degree of arsenic exposure are not necessarily the same as those used in the cited published studies. High exposure is used to denote exposure to concentrations of inorganic arsenic in drinking water at 100 µg/L or higher.
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, a metabolic intermediate of arsenic. A case–control study in Bangladesh found a dose–response relationship between the percentage of total urinary arsenic that was MMA and skin lesions in 594 cases and 1,041 population-based controls (Ahsan et al.
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The urinary arsenic concentrations in the study were all less than 50 µg/L but showed an association with nonmelanoma skin-cancer status. Other studies of lower arsenic exposure have been unable to measure skin-cancer risk at the lower concentrations precisely because of methodologic and sample-size limitations.
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Thus, it is important to evaluate modes of action underlying skin lesions and skin cancer carefully to understand how they are similar and different and their potential implications for dose–response analyses for these seemingly related end points. Key Considerations for the IRIS Assessment The committee recommends that EPA consider skin studies that have histologic specificity and that allow the separation, for example, of basal-cell carcinoma and squamous-cell carcinoma because current data suggest that they are influenced by arsenic exposure and could have different dose–response relationships.
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. In the Strong Heart Study of 3,932 American Indians 45-74 years old, baseline urinary arsenic concentrations were related to an increased hazard ratio for lung-cancer mortality of 1.56 (95% confidence interaval [CI]
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A recent study in the United States has reported an association between prenatal inorganic arsenic exposure and increased risk of respiratory disease, such as upper respiratory tract infections and colds (Farzan et al. in press)
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Cardiovascular disease may be the most important noncancer disease risk posed by environmental arsenic exposures given the high burden of cardiovascular disease worldwide. Although the current studies suggest that cardiovascular disease risk is increased by low to moderate arsenic concentrations in drinking water and possibly food, there is a need to confirm the relationship.
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. Abbreviations: BMI, body-mass index; CI, confidence interval; CVD, cardiovascular disease; eGFR, estimated glomerular filtration rate; LDL-chol, low-density lipoprotein cholesterol; NR, not reported; SES, socioeconomic status.
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In addition, ecologic studies in Taiwan reported increasing SMRs with higher categories of exposure on the basis of village median water concentrations of arsenic, and associations with well-water arsenic concentrations were supported by evi
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. The studies include an ecologic study of the proportion of private-well users that found correlations in New England where high arsenic concentrations in bedrock wells are known to occur (Ayotte et al.
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diagnosis codes commonly used in epidemiologic studies of cancers associated with arsenic exposure, urothelial cancer is coded as a subtype of renal cancer rather than bladder cancer. As noted in the committee's workshop by Cohen (2013)
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(2011) conducted a case–control study of the incidence of pathologically verified renal-cell cancer in the Taipei area of Taiwan, where arsenic concentrations in drinking water range from undetectable to 4 µg/L (average 0.7 µg/L)
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. In a cross-sectional study of a population exposed to moderate arsenic concentrations in central Taiwan (geometric mean urinary arsenic 70.6 µg/L)
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In Taiwan, the authors compared birth weights in an area (four townships with 18 villages) that had wellwater arsenic concentrations of 0.2–3,600 μg/L (30% of wells had over 50 μg/L)
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. The dose-dependent difference in birth size was obvious mainly at maternal urinary arsenic concentrations below 100 μg/L; each increase of 1 µg/L was associated with a 1.68-g reduction in birth weight.
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Infant mortality increased more clearly with increasing maternal urinary arsenic concentrations; a hazard ratio of 5.0 (95% CI 1.4– 18) was calculated in the fifth quintile of maternal urinary arsenic concentrations (268–2,019 µg/L, median 390 µg/L)
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Reconstructed cumulative and peak exposures were estimated from drinking-water arsenic concentrations and were not predictive of test scores. TABLE 2 Urinary Arsenic Concentrations in Studies of Neurotoxicity Study Urinary Arsenic, µg/L Rosado et al.
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, inverse associations between maternal urinary arsenic in pregnancy and verbal/full-scale IQ (Wechsler Preschool and Primary Scale of Intelligence) were found at the age of 5 years of age but only in girls (Hamadani et al.
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. They reported that inorganic arsenic at 50 μg/L in drinking water was associated with increased depressive behaviors.
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. Water arsenic concentrations of 10 ppb and 50 µg/L were associated with raw score losses of 3.8 and 6.4 points, respectively, but these are not equivalent to IQ points, because the WISC-III has not been standardized in Bangladesh.
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. For dose–response considerations, the Mexican studies included water arsenic concentrations of less than 10 µg/L to greater than 100 µg/L (geometric mean 24.4 µg/L)
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Colorado mg/dL, OGTT ≥ drinking water 8–19 139 1.42 0.94– 2.48 BMI, physical Ages: 20-74 200 mg/dL, or self- ≥20 141 1.55 1.00– 2.51 activity, years reported diagnosis p trend 0.04 smoking, 46% men and diabetes alcohol, medication) family history a The studies were conducted in populations with drinking water concentrations of arsenic less than 100 µg/L in the United States and were published after the NTP (2011)
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Not all epidemiologic studies have identified increases in liver cancer in relation to arsenic exposure. In a study of cancer mortality associated with arsenic in the drinking water in Cordoba, Argentina, although increases in lung and renal cancer incidence were found to be dose-dependent, mortality from liver cancer was similar in all three arsenic-exposed (low, medium, and high)
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that was the only cancer significantly increased after stratification into exposure categories. In American Indians in Arizona and North and South Dakota who participated in the Strong Heart Study, baseline urinary arsenic concentrations (median 9.7 µg/g of creatinine; interquartile range 5.8–15.6)
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. In American Indians in Arizona and North and South Dakota who participated in the Strong Heart Study, baseline urinary arsenic concentrations (median 9.7 µg/g of creatinine, interquartile range 5.8–15.6)
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The results of those studies are supported by those of a recent study conducted in the United States in which low prenatal inorganic arsenic exposure was associated with an increased risk of respiratory disease, such as upper respiratory tract infections and colds (Farzan et al.
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Those findings were supported in histologic studies and by evidence of severe immune suppression that resulted from cytokine modulation and lymphocyte death. Key Considerations for the IRIS Assessment Taken together, the evidence of a relationship between exposure to inorganic arsenic and altered immune function warrants consideration of the immune system in the IRIS assessment.
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. The first tier consists of end points that have been identified by other agencies or in systematic reviews as having a causal association with inorganic arsenic.
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