Hexavalent Chromium and Lung Cancer in the Chromate Industry: A Quantitative Risk Assessment

Abstract

The purpose of this investigation was to estimate excess lifetime risk of lung cancer death resulting from occupational exposure to hexavalent-chromium-containing dusts and mists. The mortality experience in a previously studied cohort of 2,357 chromate chemical production workers with 122 lung cancer deaths was analyzed with Poisson regression methods. Extensive records of air samples evaluated for water-soluble total hexavalent chromium were available for the entire employment history of this cohort. Six different models of exposure-response for hexavalent chromium were evaluated by comparing deviances and inspection of cubic splines. Smoking (pack-years) imputed from cigarette use at hire was included in the model. Lifetime risks of lung cancer death from exposure to hexavalent chromium (assuming up to 45 years of exposure) were estimated using an actuarial calculation that accounts for competing causes of death. A linear relative rate model gave a good and readily interpretable fit to the data. The estimated rate ratio for 1 mg/m3-yr of cumulative exposure to hexavalent chromium (as CrO3), with a lag of five years, was RR=2.44 (95% CI=1.54-3.83). The excess lifetime risk of lung cancer death from exposure to hexavalent chromium at the current OSHA permissible exposure limit (PEL) (0.10 mg/m3) was estimated to be 255 per 1,000 (95% CI: 109-416). This estimate is comparable to previous estimates by U.S. EPA, California EPA, and OSHA using different occupational data. Our analysis predicts that current occupational standards for hexavalent chromium permit a lifetime excess risk of dying of lung cancer that exceeds 1 in 10, which is consistent with previous risk assessments.

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

“…This shape suggests to replace the non-parametric dose-response model (1) through a log-linear dose-response relation. This means we replace the smooth curve s(x) in Park et al 1 by the log-linear shape…”

“…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…”

“…1 The values given are based on an assumed dose-response relationship and an accepted excess lifetime lung cancer mortality risk. Assuming 4 additional lung cancer cases among 1000 workers as lifetime risk (40 years of exposure) the exposure limit value is fixed at the concentration of 1 μg/m 3 , which would translate into 52 lung cancer cases compared to 48 for a non-exposed population.…”

“…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.…”

“…An alternative modelling approach is based on Poisson regression models, which in statistical terms are more natural for modelling count data. 9 This approach has been pursued for example by Park et al 1 and Becher and Wahrendorf 10 to provide an overview of the different modelling approaches to study and analyse dose-response data.…”