Human Studies Do Not Support the Methylation Threshold Hypothesis for the Toxicity of Inorganic Arsenic

Hopenhayn‐Rich, Claudia; Smith, Allan H.; Goeden, Helen M.

doi:10.1006/enrs.1993.1024

Cited by 141 publications

(74 citation statements)

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“…Percentages of urinary InAs were also within the range of a number of studies including arsenic exposures of background, occupational, environmental, and experimental groups (15).…”

Section: Discussionsupporting

confidence: 60%

“…We also omitted one other sample from Toconao, an outlier with an unusually high MMA:DMA ratio of 2.4 (several standard deviations away from the mean (0. 15) for that town, possibly due to the fact that the TotAs was very low (4.4 pg/i) and species were close to their detection limits.…”

mentioning

confidence: 83%

“…Previously we presented the results of several studies reporting speciated urinary arsenic measures and showed that population studies do not support the methylation threshold hypothesis (15 Articles -Arsenic methylation in a highly exposed population used drinking water with a weighted average concentration of around 500 pg/l, which would result in urine levels above those published for previous occupational or environmental studies.…”

mentioning

confidence: 98%

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Methylation Study of a Population Environmentally Exposed to Arsenic in Drinking Water

Hopenhayn‐Rich¹,

Biggs²,

Smith³

et al. 1996

Environmental Health Perspectives

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“…Percentages of urinary InAs were also within the range of a number of studies including arsenic exposures of background, occupational, environmental, and experimental groups (15).…”

Section: Discussionsupporting

confidence: 60%

mentioning

confidence: 83%

mentioning

confidence: 98%

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Methylation Study of a Population Environmentally Exposed to Arsenic in Drinking Water

Hopenhayn‐Rich¹,

Biggs²,

Smith³

et al. 1996

Environmental Health Perspectives

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“…In humans, this process is not complete, and some arsenic remains as either inorganic arsenic or monomethylarsonate. Typically, ingested inorganic arsenic is excreted as 10% to 20% inorganic arsenic, 10% to 15% monomethylarsonate, and 60% to 75% dimethylarsinate (17). However, large interindividual variations exist (18).…”

Section: Introductionmentioning

confidence: 99%

Intraindividual Variability in Arsenic Methylation in a U.S. Population

Steinmaus

Yuan

Kalman

et al. 2005

Cancer Epidemiology, Biomarkers &Amp; Prevention

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Several recent investigations have reported associations between a reduced capacity to fully methylate inorganic arsenic and increased susceptibility to arsenic-caused cancer. In these studies, methylation patterns were based on a single assessment of urinary arsenic metabolites collected at the time of cancer diagnosis. However, the latency of arsenic-caused cancer may be several decades, and the extent to which a recent measurement can be used to estimate a person's past methylation pattern is unknown. In this investigation, the distribution of urinary inorganic arsenic, monomethylarsonate, and dimethylarsinate was used to assess intraindividual variation in methylation capacity in 81 subjects with low to moderate arsenic exposures. Multiple urine samples were collected from each subject over a 1-year period. Duplicate analyses done on 27 samples were used to assess laboratory measurement imprecision. The intraclass correlation coefficients (ICC) for the proportion of urinary arsenic as inorganic arsenic, monomethylarsonate, and dimethylarsinate in samples taken an average of 258 days apart, were 0.45 [95% confidence interval (95% CI), 0.23-0.63] 0.46 (95% CI, 0.24-0.64), and 0.49 (95% CI, 0.28-0.66). In analyses of duplicate samples, ICCs for the concentration of arsenic species ranged from 0.87 to 0.93, whereas ICCs for species proportions ranged from 0.63 to 0.76. These data suggest that individual methylation patterns remain fairly stable over time, although variability due to measurement imprecision or intraindividual changes over time does occur. This variability could lead to misclassification of methylation patterns and could bias relative risk estimates in studies of methylation and cancer towards the null.

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“…Carlson-Lynch et al (14) presented critical commentary on use of the Taiwanese data set for risk assessment at low doses in areas other than Taiwan. This commentary took particular aim at the report of Smith et al (4), which estimated rather high internal cancer risk rates using linear dose-response extrapolation from the Taiwan data set, and the review of Hopenhayn-Rich et al (17), which showed that detoxification of inorganic arsenic in humans via biomethylation is efficient up to rather high intakes, suggesting that impaired biomethylation and detoxification among the exposed Taiwanese was not necessarily a factor in their cancer rates. A subject of debate, as noted below, is the extent to which methylation/detoxification attenuates cancer risk.…”

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confidence: 99%

Risk and revisionism in arsenic cancer risk assessment.

Mushak¹,

Crocetti²

1995

Environ Health Perspect

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Oral exposures of nonoccupational populations to environmental inorganic arsenic are associated with skin and internal cancers as well as various noncarcinogenic effects. Cancer risk assessments have been based largely on epidemiological studies of a large population exposed to inorganic arsenic in well water in Taiwan. Criticisms and skepticism of the use of the Taiwanese data for estimating arsenic cancer risks outside of Taiwan, including potential use by the U.S. Environmental Protection Agency for regulatory purposes, have been expressed on various grounds. The nature and extent of such criticisms have sharpened with recent findings in the exposed Taiwanese of increased incidence of internal cancers (bladder, kidney, liver, and lung), in addition to already-observed skin cancer, coupled with a good likelihood that these findings will produce more stringent arsenic regulation in the United States and elsewhere. These criticisms collectively posit a revisionist view that: 1) cancer incidence among the Taiwanese was amplified by a number of host and environmental factors not applicable elsewhere, 2) the cancer dose-response curve may not be linear at the lower exposures elsewhere, and 3) there is a toxicokinetic and metabolic threshold to cancer risk that was exceeded by the Taiwanese. However, a number of the arguments against wide use of the Taiwanese data are flawed and subject to challenge. We explore some of these arguments and their critical evaluation, particularly as they concern certain exposure, metabolic, and nutritional determinants of the cancer risk of inorganic arsenic in the Taiwanese.

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Human Studies Do Not Support the Methylation Threshold Hypothesis for the Toxicity of Inorganic Arsenic

Cited by 141 publications

References 0 publications

Methylation Study of a Population Environmentally Exposed to Arsenic in Drinking Water

Methylation Study of a Population Environmentally Exposed to Arsenic in Drinking Water

Intraindividual Variability in Arsenic Methylation in a U.S. Population

Risk and revisionism in arsenic cancer risk assessment.

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