Evaluation of the Exposure—Response Relationship of Lung Cancer Mortality and Occupational Exposure to Hexavalent Chromium Based on Published Epidemiological Data

Wijngaarden, Edwin van; Mundt, Kenneth A.; Luippold, Rose S.

doi:10.1080/15401420490426972

Cited by 7 publications

(4 citation statements)

References 24 publications

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“…The contrasts analyzed here for threshold were model‐dependent; with some nonlinear model forms, discerning a real threshold might be quite difficult. On the other hand, approximate linearity of the lung cancer response in relation to cumulative exposure is quite well established for hexavalent chromium above low exposure levels (>25 μg/m 3 CrO 3 ) or low cumulative exposures (>0.1 mg‐yr/m 3 ) ( 7,8,18 ) and is supported by the fractional polynomials analyses reported here. A large intensity threshold, comparable to average exposure levels (40 μg/m 3 CrO 3 ), for example, should be identifiable.…”

Section: Discussionsupporting

confidence: 80%

A Search for Thresholds and Other Nonlinearities in the Relationship Between Hexavalent Chromium and Lung Cancer

Park¹,

Stayner²

2005

Risk Analysis

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The exposure-response relationship for airborne hexavalent chromium exposure and lung cancer mortality is well described by a linear relative rate model. However, categorical analyses have been interpreted to suggest the presence of a threshold. This study investigates nonlinear features of the exposure response in a cohort of 2,357 chemical workers with 122 lung cancer deaths. In Poisson regression, a simple model representing a two-step carcinogenesis process was evaluated. In a one-stage context, fractional polynomials were investigated. Cumulative exposure dose metrics were examined corresponding to cumulative exposure thresholds, exposure intensity (concentration) thresholds, dose-rate effects, and declining burden of accumulated effect on future risk. A simple two-stage model of carcinogenesis provided no improvement in fit. The best-fitting one-stage models used simple cumulative exposure with no threshold for exposure intensity and had sufficient power to rule out thresholds as large as 30 microg/m3 CrO3 (16 microg/m3 as Cr+6) (one-sided 95% confidence limit, likelihood ratio test). Slightly better-fitting models were observed with cumulative exposure thresholds of 0.03 and 0.5 mg-yr/m3 (as CrO3) with and without an exposure-race interaction term, respectively. With the best model, cumulative exposure thresholds as large as 0.4 mg-yr/m3 CrO3 were excluded (two-sided upper 95% confidence limit, likelihood ratio test). A small departure from dose-rate linearity was observed, corresponding to (intensity)0.8 but was not statistically significant. Models in which risk-inducing damage burdens declined over time, based on half-lives ranging from 0.1 to 40 years, fit less well than assuming a constant burden. A half-life of 8 years or less was excluded (one-sided 95% confidence limit). Examination of nonlinear features of the hexavalent chromium-lung cancer exposure response in a population used in a recent risk assessment supports using the traditional (lagged) cumulative exposure paradigm: no intensity (concentration) threshold, linearity in intensity, and constant increment in risk following exposure.

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Section: Discussionsupporting

confidence: 80%

A Search for Thresholds and Other Nonlinearities in the Relationship Between Hexavalent Chromium and Lung Cancer

Park¹,

Stayner²

2005

Risk Analysis

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“…The model equations described in previous studies7 8 21 22 were used to estimate the effect of cumulative exposure d (f-y/ml) on λ 0 . The multiplicative models can be represented mathematically as:

λ = λ_{0} \times f (d)

where λ is the estimated incidence rate for the health effect of exposure d , f( d ) is a function of cumulative exposure to asbestos d , and λ 0 is the baseline incidence rate modelled as a log linear function of the covariates including age (13 levels: <25, 25–29, 30–34, 35–39…, ≥80), calendar time period (1972–1979, 1980–1989, 1990–1999, 2000–2006) and smoking.…”

Section: Methodsmentioning

confidence: 99%

Exposure–response relationship between chrysotile exposure and mortality from lung cancer and asbestosis

Deng

Wang

et al. 2011

Occup Environ Med

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“…Despite the relatively clear epidemiological evidence that these genotoxic substances are human lung carcinogens, some epidemiological studies demonstrate that lung cancer risks are not increased among all groups of exposed workers, and may be greatest or even limited to those most highly exposed (2)(3)(4). This suggests that for at least some of these substances there are exposure thresholds above which risk is increased, possibly reflecting the impact of one or more protective mechanisms including DNA and/or cellular repair, clearance, dissolution, chemical reduction or transformation, etc., that reduce or eliminate the carcinogenic responses to the substances.…”

Section: Introductionmentioning

confidence: 99%

Carcinogenicity of Poorly Soluble Low Toxicity Particles: Commentary on Epidemiology as a Risk Assessment “Reality Check”

Mundt

Santamaria

Thompson

et al. 2022

Front. Public Health

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Inhaled particles that are poorly soluble or insoluble and of low toxicity (“poorly soluble low toxicity” or “PSLT” particles), can accumulate in the lung and at lung overload levels induce lung cancers in rats. The question of whether PSLT particles increase lung cancer risk in humans is complicated by large differences between rats and humans and the relatively large particle doses administered in animal studies even when compared with heavy human occupational exposures. We review the findings of epidemiological studies on occupational exposure to each of three different PSLT particles (carbon black, talc and taconite). The epidemiological evidence indicates that at even very high occupational exposure levels at which non-malignant respiratory diseases including pneumoconiosis and even talcosis are observed, lung cancer risks appear not to be elevated. Although positive human cancer risks might be predicted based on extrapolation from overload doses in rats to relevant exposures in humans, the epidemiological “reality check” based on the three examples indicates that these PSLT particles are unlikely to increase lung cancer risk in humans even at high occupational levels of exposure. Therefore, we propose that careful evaluation of the epidemiological evidence can serve as a “reality check” for human risk assessment and help balance the risk evaluation process.

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Evaluation of the Exposure—Response Relationship of Lung Cancer Mortality and Occupational Exposure to Hexavalent Chromium Based on Published Epidemiological Data

Cited by 7 publications

References 24 publications

A Search for Thresholds and Other Nonlinearities in the Relationship Between Hexavalent Chromium and Lung Cancer

A Search for Thresholds and Other Nonlinearities in the Relationship Between Hexavalent Chromium and Lung Cancer

Exposure–response relationship between chrysotile exposure and mortality from lung cancer and asbestosis

Carcinogenicity of Poorly Soluble Low Toxicity Particles: Commentary on Epidemiology as a Risk Assessment “Reality Check”

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