Suchergebnisse

Multistage models are frequently applied in carcinogenic risk assessment. In their simplest form, these models relate the probability of tumor presence to some measure of dose. These models are then used to project the excess risk of tumor occurrence at doses frequently well below the lowest experimental dose. Upper confidence limits on the excess risk associated with exposures at these doses are then determined. A likelihood‐based method is commonly used to determine these limits. We compare this method to two computationally intensive "bootstrap" methods for determining the 95% upper confidence limit on extra risk. The coverage probabilities and bias of likelihood‐based and bootstrap estimates are examined in a simulation study of carcinogenicity experiments. The coverage probabilities of the nonparametric bootstrap method fell below 95% more frequently and by wider margins than the better‐performing parametric bootstrap and likelihood‐based methods. The relative bias of all estimators are seen to be affected by the amount of curvature in the true underlying dose‐response function. In general, the likelihood‐based method has the best coverage probability properties while the parametric bootstrap is less biased and less variable than the likelihood‐based method. Ultimately, neither method is entirely satisfactory for highly curved dose‐response patterns.

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.