Response to Druwe and Burgoon

Cohen, Samuel M.; Arnold, Lora L.; Klaunig, James E.; Goodman, Jay I.

doi:10.1007/s00204-016-1823-7

Cited by 6 publications

(2 citation statements)

References 8 publications

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“…Our conclusions were consistent with the findings of Waalkes et al (2014), which have subsequently been called into question by Cohen et al ( , 2015. In their Letter to the Editor, Cohen et al (2016) raised several concerns with our analysis, however none of their concerns were sufficient to refute the conclusion of our analysis of the Waalkes et al (2014) and Tokar et al (2011Tokar et al ( , 2012 data. Specifically, that arsenic related lung tumors in CD-1 mice result from the doses administered in the Waalkes study, Cohen et al made points seeking clarification of our analyses.…”

supporting

confidence: 85%

Response to Cohen et al. (2016) regarding response to Druwe and Burgoon

Druwe

Burgoon

2016

Arch Toxicol

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selection. The formulas and rationale we used were published along with the raw data needed to repeat the analysis as a JUPYTER notebook, which we referenced in the first letter and again above. A JUPYTER notebook is an web based notebook that contains both computer code (e.g., such as that run in R) and rich text elements such as figures, equations etc. A JUPYTER document are humans-readable documents that can also execute computer code simultaneously. In this way, we have made all of our analyses and the data completely transparent and accessible in our analysis report.Cohen et al.'s second concern expressed that we did not provide a rationale for the use of the Bernoulli distribution. The Bernoulli distribution is discussed in the statistical literature as the standard distribution when dealing with binary cases, such as success/failure, heads/tails, cancer/ no-cancer (Freedman et al. 2007;Kruske 2011). The case of the Waalkes and Tokar data is a classic binary case of tumor/no tumor, making the Bernoulli distribution the simplest distribution with the fewest number of parameters choices.Cohen et al.'s third concern expressed that our ROPE interval was arbitrary. We provided a rationale for the ROPE analysis in the report referenced in the previous letter and again above. We stated, "Expanding the ROPE slightly, such as to ±0.10, still would not bring the 95 % HDI within the ROPE. We do not believe that a ±10 % rope is justified, when dealing with tumor incidences in the control population that are approximately 28 %. Specifically, we do not believe it is biologically plausible that a tumor incidence that spans from 18 to 38 % can be considered practically equivalent, whereas one that spans from 23 to 33 % is."We also wanted to address Cohen et al.'s contention that the Haseman criteria should apply to a common tumor as

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supporting

confidence: 85%

Response to Cohen et al. (2016) regarding response to Druwe and Burgoon

Druwe

Burgoon

2016

Arch Toxicol

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“…Higher incidence and prevalence rates of skin cancers, as well as intraepidermal carcinomas have been linked to acute arsenic exposure . A variety of skin lesions are often considered as sensitive biomarkers of susceptibility and effect and may coexist in many regions, where arsenicosis is prevalent . The skin is a target organ of arsenic poisoning but not considered as the primary route of exposure .…”

Section: Epidemiology Of Arsenic Toxicitymentioning

confidence: 99%

State of the science review of the health effects of inorganic arsenic: Perspectives for future research

Tchounwou

Yedjou

Udensi

et al. 2018

Environmental Toxicology

131

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Human exposure to inorganic arsenic (iAs) is a global health issue. Although there is strong evidence for iAs-induced toxicity at higher levels of exposure, many epidemiological studies evaluating its effects at low exposure levels have reported mixed results. We comprehensively reviewed the literature and evaluated the scientific knowledge on human exposure to arsenic, mechanisms of action, systemic and carcinogenic effects, risk characterization, and regulatory guidelines. We identified areas where additional research is needed. These priority areas include: (1) further development of animal models of iAs carcinogenicity to identify molecular events involved in iAs carcinogenicity; (2) characterization of underlying mechanisms of iAs toxicity; (3) assessment of genderspecific susceptibilities and other factors that modulate arsenic metabolism; (4) sufficiently powered epidemiological studies to ascertain relationship between iAs exposure and reproductive/ developmental effects; (5) evaluation of genetic/epigenetic determinants of iAs effects in children;and (6) epidemiological studies of people chronically exposed to low iAs concentrations.

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Dose-response for assessing the cancer risk of inorganic arsenic in drinking water: the scientific basis for use of a threshold approach

Tsuji

Chang

Gentry³

et al. 2019

Critical Reviews in Toxicology

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The biologic effects of inorganic arsenic predominantly involve reaction of the trivalent forms with sulfhydryl groups in critical proteins in target cells, potentially leading to various toxicologic events including cancer. This mode of action is a threshold process, requiring sufficient concentrations of trivalent arsenic to disrupt normal cellular function. Nevertheless, cancer risk assessments for inorganic arsenic have traditionally utilized various dose-response models that extrapolate risks from high doses assuming low-dose linearity without a threshold. We present here an approach for a cancer risk assessment for inorganic arsenic in drinking water that involves considerations of this threshold process. Extensive investigations in mode of action analysis, in vitro studies (>0.1 mM), and in animal studies (>2 mg/L in drinking water or 2 mg/kg of diet), collectively indicate a threshold basis for inorganic arsenic-related cancers. These studies support a threshold for the effects of arsenic in humans of 50-100 mg/L in drinking water (about 65 mg/L). We then evaluate the epidemiology of cancers of the urinary bladder, lung, and skin and non-cancer skin changes for consistency with this calculated value, focusing on studies involving low-level exposures to inorganic arsenic primarily in drinking water (approximately <150 mg/L). Based on the relevant epidemiological studies with individual-level data, a threshold level for inorganic arsenic in the drinking water for these cancers is estimated to be around 100 mg/L, with strong evidence that it is between 50 and 150 mg/L, consistent with the value calculated based on mechanistic, in vitro and in vivo investigations. This evaluation provides an alternative mode of action-based approach for assessing health-protective levels for oral arsenic exposure based on the collective in vitro, in vivo, and human evidence rather than the use of a linear low-dose extrapolation based on default assumptions and theories.

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Response to Druwe and Burgoon

Cited by 6 publications

References 8 publications

Response to Cohen et al. (2016) regarding response to Druwe and Burgoon

Response to Cohen et al. (2016) regarding response to Druwe and Burgoon

State of the science review of the health effects of inorganic arsenic: Perspectives for future research

Dose-response for assessing the cancer risk of inorganic arsenic in drinking water: the scientific basis for use of a threshold approach

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