Documents Dankovic, David 4 results

"The uncertainty factor concept is integrated into health risk assessments for all aspects of public health practice, including by most organizations that derive occupational exposure limits. The use of uncertainty factors is predicated on the assumption that a sufficient reduction in exposure from those at the boundary for the onset of adverse effects will yield a safe exposure level for at least the great majority of the exposed population, including vulnerable subgroups. There are differences in the application of the uncertainty factor approach among groups that conduct occupational assessments; however, there are common areas of uncertainty which are considered by all or nearly all occupational exposure limit-setting organizations. Five key uncertainties that are often examined include interspecies variability in response when extrapolating from animal studies to humans, response variability in humans, uncertainty in estimating a no-effect level from a dose where effects were observed, extrapolation from shorter duration studies to a full life-time exposure, and other insufficiencies in the overall health effects database indicating that the most sensitive adverse effect may not have been evaluated. In addition, a modifying factor is used by some organizations to account for other remaining uncertainties-typically related to exposure scenarios or accounting for the interplay among the five areas noted above. Consideration of uncertainties in occupational exposure limit derivation is a systematic process whereby the factors applied are not arbitrary, although they are mathematically imprecise. As the scientific basis for uncertainty factor application has improved, default uncertainty factors are now used only in the absence of chemical-specific data, and the trend is to replace them with chemical-specific adjustment factors whenever possible. The increased application of scientific data in the development of uncertainty factors for individual chemicals also has the benefit of increasing the transparency of occupational exposure limit derivation. Improved characterization of the scientific basis for uncertainty factors has led to increasing rigor and transparency in their application as part of the overall occupational exposure limit derivation process."

"Objectives The purpose of this study was to evaluate empirically the relevance of animal-bioassay-based models for predicting human risks from exposure to 1,3-butadiene (BD) using epidemiologic data.Methods Relative-risk results obtained with a regression model in a recent epidemiologic study were used to estimate leukemia risk for occupational and environmental exposures to BD and to compare these estimates with those previously derived from an analysis of animal bioassay data.Results The estimates of risk were found to be highly dependent on the model used when low levels of exposure were evaluated that are of environmental concern, but not at the levels of occupational concern. For example, at the level (1 part per million) of the recently revised standard of the Occupational Safety and Health Administration in the United States the estimates of lifetime excess risk ranged from 1 to 8 per 1000 workers. The range of the risk estimates derived from the epidemiologic models was remarkably similar to the range of risk estimates for occupational exposures (1 to 9 per thousand) previously developed by Dankovic et al in 1993 from an analysis of a mouse bioassay study for lymphocytic lymphoma.Conclusions Results for BD seem to provide another example of a high degree of concordance between the risk predictions from models of toxicologic and epidemiologic data, particularly at occupational levels of exposure."

Several quantitative risk assessment models have been published for occupational and environmental exposures to diesel exhaust particles (DEP). These risk assessment models are reviewed and applied to predict lung cancer risks for miners exposed to DEP. The toxicologically based unit risk estimates varied widely (from 2 to 220 ? 10-6 per g/m3). The epidemiologically based unit risk estimates were less variable and suggest higher risks (from 100 to 920 ? 10-6 per g/m3). The wide range of risk estimates derived from these analyses reflects the strong assumptions and large uncertainties underlying these models. All of the models suggest relatively high risks (i.e., >1/1,000) for miners with long-term exposures greater than 1,000 g/m3. This is not surprising, given the fact that miners may be exposed to DEP concentrations similar to those that induced lung cancer in rats and mice, and substantially higher than the exposure concentrations in the positive epidemiologic studies.

The evidence for the association between occupational chrysotile (12001295) exposure and cancer was reviewed to evaluate the amphibole hypothesis which proposed that the mesotheliomas observed among workers exposed to chrysotile may actually be caused by contamination by relatively low concentrations (below 1%) of tremolite (77536686) fibers. The review considered evidence obtained in studies investigating chrysotile lung burdens, epidemiologic and laboratory animal studies investigating asbestos carcinogenicity, and mechanistic studies. Low concentrations of chrysotile fibers have been found in the lungs of asbestos workers, even those who worked primarily in chrysotile producing industries. Unexpectedly high concentrations of amphibole asbestos (1332214) forms were found. These findings provided the primary basis for the amphibole hypothesis. Most case/control studies investigating associations between asbestos lung burdens and mesothelioma risk have found clear dose response relationships with amphibole lung burdens, but not chrysotile lung burdens. Some studies, however, have found associations between mesothelioma risk and chrysotile lung burdens. Both epidemiological and experimental studies have shown that chrysotile can cause lung cancer and mesothelioma and that its carcinogenic activity was not due to contamination with tremolite. Some of the epidemiologic evidence has indicated that chrysotile may be less potent than the amphiboles in causing mesothelioma. The experimental animal evidence showed than when expressed on a per weight basis, chrysotile fibers are as at least as potent as amphibole asbestos fibers in causing lung cancer. The authors conclude that the toxicologic and epidemiologic literature strongly support the view that occupational exposure to chrysotile increases the risk of lung cancer and mesothelioma. It is considered prudent that chrysotile be treated with the same level of concern as the amphibole forms of asbestos.