Silica exposure and silicosis: effect of mixed exposures.
Ramachandran-G; Alexander-BH; Banerjee-S; Rice-C
NIOSH 2005 Jan; :1-67
The quantitative relationship between exposure to crystalline silica and development of silicosis is uncertain despite a number of studies addressing the problem. The uncertainty is due to the following reasons: (a) the exposure reconstructions were based on sparse data with tremendous uncertainties; (b) dose reconstructions, to estimate the cumulative lung burden of the worker, did not account for retention and clearance of inhaled dusts; (c) exposure reconstructions for silica, a highly toxic dust, did not account for simultaneous exposures to less toxic dusts, (non-silica dusts). The purpose of this study was to obtain the quantitative dose-response relationship between crystalline silica and silicosis in a manner that addressed the above issues. The North Carolina Dusty Trades program provides a large dataset of human exposures to silica and nonsilica dust and silicosis from 1935-1980. Pharmacokinetic modeling was used to estimate the cumulative lung dose of silica and non-silica dust and time to macrophage overload in the presence of this mixed exposure. A case-control study was conducted to compare silicotics and disease-free referents. Conditional logistic regression models were developed to estimate odds ratios for the risk of silicosis for the given exposure metric. The independent and joint effects of cumulative silica and non-silica exposures and measures of lung burden were modeled to determine whether the cumulative non-silica exposure modifies the risk of silicosis among exposed workers. The cases had a much higher cumulative silica and non-silica dust exposure than the controls. The median silica exposures in the cases was roughly four times the exposure for the controls, however the non-silica dusts were less than twice as high. The median time from first employment to the estimated time of lung macrophage overload was much lower in the cases. The associations between silica exposure and non-silica dust exposure were maintained when these covariates were considered together in a model. This is consistent with and suggestive of the first study hypothesis that "A cumulative exposure metric, which includes both silica and non-silica dusts, is more related to the development of silicosis than cumulative silica exposure alone". These findings illustrate that the effect of silica exposures are modified by the presence of other dusts, and should be accounted for in the epidemiological analysis. The time to overload was strongly associated with silicosis development when cumulative exposures to silica and non-silica dust were taken into account. The odds ratios for silica and non-silica dust exposure were, as expected, attenuated when this third metric of exposure was included in the model. Thus, our second hypothesis that "The time to macrophage overload is a function of both silica and non-silica exposure, and is related to the development of silicosis" is supported by this analysis of the data. When the months to overload was entered in the model, both silica exposures and months to overload were significantly correlated with development of silicosis. The longer it took for a worker to reach overload the lower the risk of silicosis. These models offer additional evidence that the time to macrophage overload influences the development of silicosis, and that earlier exposure appears to be more important than later exposures.
Silicosis; Silica-dusts; Respiratory-system-disorders; Pulmonary-system-disorders; Lung-burden; Lung-disease; Lung-disorders; Lung-fibrosis; Fibrogenesis; Fibrogenicity; Fibrous-dusts; Analytical-processes; Models; Statistical-analysis; Epidemiology
Dr. G. Ramachandran, Division of Environmental Health Sciences, School of Public Health, University of Minnesota, MMC 807, 420 Delaware Street SE, Minneapolis, MN 55455
Final Grant Report
NTIS Accession No.
Work Environment and Workforce: Mixed Exposures
National Institute for Occupational Safety and Health
University of Minnesota - Twin cities