Dose‐Response and Risk Assessment of Airborne Hexavalent Chromium and Lung Cancer Mortality

Abstract

This study evaluates the dose-response relationship for inhalation exposure to hexavalent chromium [Cr(VI)] and lung cancer mortality for workers of a chromate production facility, and provides estimates of the carcinogenic potency. The data were analyzed using relative risk and additive risk dose-response models implemented with both Poisson and Cox regression. Potential confounding by birth cohort and smoking prevalence were also assessed. Lifetime cumulative exposure and highest monthly exposure were the dose metrics evaluated. The estimated lifetime additional risk of lung cancer mortality associated with 45 years of occupational exposure to 1 microg/m3 Cr(VI) (occupational exposure unit risk) was 0.00205 (90%CI: 0.00134, 0.00291) for the relative risk model and 0.00216 (90%CI: 0.00143, 0.00302) for the additive risk model assuming a linear dose response for cumulative exposure with a five-year lag. Extrapolating these findings to a continuous (e.g., environmental) exposure scenario yielded an environmental unit risk of 0.00978 (90%CI: 0.00640, 0.0138) for the relative risk model [e.g., a cancer slope factor of 34 (mg/kg-day)-1] and 0.0125 (90%CI: 0.00833, 0.0175) for the additive risk model. The relative risk model is preferred because it is more consistent with the expected trend for lung cancer risk with age. Based on statistical tests for exposure-related trend, there was no statistically significant increased lung cancer risk below lifetime cumulative occupational exposures of 1.0 mg-yr/m3, and no excess risk for workers whose highest average monthly exposure did not exceed the current Permissible Exposure Limit (52 microg/m3). It is acknowledged that this study had limited power to detect increases at these low exposure levels. These cancer potency estimates are comparable to those developed by U.S. regulatory agencies and should be useful for assessing the potential cancer hazard associated with inhaled Cr(VI).

Exploring the statistical uncertainty in acceptable exposure limit values for hexavalent chromium exposure

“…These are incorporated in the data by providing expected numbers of lung cancer cases for a reference population, that is, for a nonexposed cohort. Let e i denote these expected numbers of cases which are also provided by Crump et al 7 and which are based on the mortality in the underlying population. These quantities now allow to specify the Poisson model to…”

“…Besides the Poisson model it is possible to model the SMR directly. Like in Crump et al 7 we look at the weighted linear model…”

“…They included the Painesville and Baltimore cohort studies data using a linear SMR model. They proposed a combined estimation by taking the simple average of the fitted coefficients β x for the Painesville data ( = 0.68, see Crump et al 7 ) and the Baltimore data ( = 2.82, see also Park et al 1 ) leading toβ x;combined ¼ 1:75 ¼ ð0:68þ2:82Þ…”

“…We will first constrain the investigation to the Painesville study and simulate from the fitted log-linear Poisson model (2). To be specific, we take both, the categorised exposure levels as well as the expected number of cases published in Crump et al 7 We insert these values in model (2) and simulate (bootstrap) observed cases using the estimated parameter values. To account for overdispersion we do not draw from a Poisson model directly but draw the observed cases from a negative-binomial model, such that the mean structure follows the fitted model (2) but the variance is inflated by the fitted overdispersion parameter.…”

“…Two cohort studies are playing a central role in the analyses as they account for smoking status among the workers. The first, the so-called Baltimore cohort study, was first analysed by Gibb et al 4 with follow ups by Park et al, 1,5 and recently by Haney et al 6 The second cohort study, the so-called Painesville study was presented by Crump et al 7 and Luippold et al 8 We here refer to both studies and analyse the published summarised data with respect to quantifying the uncertainty of derived exposure limit values.…”