Analysis of Regulatory Inhalation Unit Risk Estimates for Cobalt: Comparison to Epidemiological Data

Several cancer potency estimates have been proposed by regulatory agencies to characterize the dose response of cobalt and/or cobalt compounds.   The objective of this research is to investigate whether these proposed cancer potency estimates for certain cobalt substances align with the available epidemiology literature. After review of the epidemiological literature, we identified a study appropriate for our analysis. We established whether our identified study was adequately powered to detect an elevated lung cancer risk. The power analysis assumed a Poisson distribution and used a one-sided significance level of 0.05. Lung tumors in animals served as the basis for cancer potency estimates for several regulatory bodies. The study population from our identified study was used to calculate predicted excess lung cancer deaths using potency values reported by four regulatory organizations, which were then compared to observed lung cancer deaths. Monte Carlo methods were used to estimate sample size and cobalt exposure distribution of the highest exposure group. We determined that the our identified study has ≥ 98% statistical power to detect a 1.5-fold or greater increase in lung cancer due to cobalt exposure in all but the lowest exposure group and all four exposure groups had 100% statistical power to detect a 2.0-fold or greater increase in lung cancer due to cobalt exposure. Cobalt exposure at the estimated median of the highest exposure group resulted in hypothetical standardized mortality ratios (SMR) estimated from the regulatory potency values ranging from 3.54 to 8.61 compared to an observed SMR of 1.15 (95% CI: 0.92-1.43) in our identified study. On the basis of this analysis, the cancer potency estimates proposed by the included regulatory organizations are likely overestimations of excess lifetime human cancer risk after cobalt inhalation exposure.