Stochastic estimates of exposure and cancer risk from carbon tetrachloride released to the air from the rocky flats plant.

Carbon tetrachloride is a degreasing agent that was used at the Rocky Flats Plant (RFP) in Colorado to clean product components and equipment. The chemical is considered a volatile organic compound and a probable human carcinogen. During the time the plant operated (1953-1989), most of the carbon tetrachloride was released to the atmosphere through building exhaust ducts. A smaller amount was released to the air via evaporation from open-air burn pits and ground-surface discharge points. Airborne releases from the plant were conservatively estimated to be equivalent to the amount of carbon tetrachloride consumed annually by the plant, which was estimated to be between 3.6 and 180 Mg per year. This assumption was supported by calculations that showed that most of the carbon tetrachloride discharged to the ground surface would subsequently be released to the atmosphere. Atmospheric transport of carbon tetrachloride from the plant to the surrounding community was estimated using a Gaussian Puff dispersion model (RATCHET). Time-integrated concentrations were estimated for nine hypothetical but realistic exposure scenarios that considered variation in lifestyle, location, age, and gender. Uncertainty distributions were developed for cancer slope factors and atmospheric dispersion factors. These uncertainties were propagated through to the final risk estimate using Monte Carlo techniques. The geometric mean risk estimates varied from 5.2 x 10(-6) for a hypothetical rancher or laborer working near the RFP to 3.4 x 10(-9) for an infant scenario. The distribution of incremental lifetime cancer incidence risk for the hypothetical rancher was between 1.3 x 10(-6) (5% value) and 2.1 x 10(-5) (95% value). These estimates are similar to or exceed estimated cancer risks posed by releases of radionuclides from the site.

Chronic beryllium disease and cancer risk estimates with uncertainty for beryllium released to the air from the Rocky Flats Plant.

Beryllium was released into the air from routine operations and three accidental fires at the Rocky Flats Plant (RFP) in Colorado from 1958 to 1989. We evaluated environmental monitoring data and developed estimates of airborne concentrations and their uncertainties and calculated lifetime cancer risks and risks of chronic beryllium disease to hypothetical receptors. This article discusses exposure-response relationships for lung cancer and chronic beryllium disease. We assigned a distribution to cancer slope factor values based on the relative risk estimates from an occupational epidemiologic study used by the U.S. Environmental Protection Agency (EPA) to determine the slope factors. We used the regional atmospheric transport code for Hanford emission tracking atmospheric transport model for exposure calculations because it is particularly well suited for long-term annual-average dispersion estimates and it incorporates spatially varying meteorologic and environmental parameters. We accounted for model prediction uncertainty by using several multiplicative stochastic correction factors that accounted for uncertainty in the dispersion estimate, the meteorology, deposition, and plume depletion. We used Monte Carlo techniques to propagate model prediction uncertainty through to the final risk calculations. We developed nine exposure scenarios of hypothetical but typical residents of the RFP area to consider the lifestyle, time spent outdoors, location, age, and sex of people who may have been exposed. We determined geometric mean incremental lifetime cancer incidence risk estimates for beryllium inhalation for each scenario. The risk estimates were < 10(-6). Predicted air concentrations were well below the current reference concentration derived by the EPA for beryllium sensitization.

Inhalation of chrysotile asbestos induces rapid cellular proliferation in small pulmonary vessels of mice and rats.

Asbestos inhalation in mice and rats causes a rapid proliferative response in epithelial and interstitial cells, followed by the development of an interstitial lesion at the first alveolar duct bifurcations where fiber deposition and alveolar macrophage accumulation occur. Here we report that endothelial and smooth muscle cells of arterioles and venules near the bifurcations incorporated significantly increased levels of 3H-TdR 19 to 72 hours after chrysotile exposure. As many as 28% of the vessels had labeled cells 31 hours after exposure. No labeled cells were observed in vessels from sham-exposed or iron-exposed controls. This proliferative response resulted in a doubling of both the number of smooth muscle cells and the thickness of the smooth muscle cell layer, determined by ultrastructural morphometry 1 month after exposure. The fact that a variety of cell types incorporates 3H-TdR so rapidly after asbestos inhalation leads us to speculate that the response involves the release of diffusible growth factors.

Tritiated thymidine incorporation and the development of an interstitial lesion in the bronchiolar-alveolar regions of the lungs of normal and complement deficient mice after inhalation of chrysotile asbestos.

Inhaled asbestos causes the proliferation of bronchiolar-alveolar epithelial and interstitial cells in rats and mice 19 to 72 hours after a single 5-hour exposure. This condition is associated with rapid macrophage accumulation and development of an interstitial fibrotic lesion at alveolar duct bifurcations. In an attempt to define the mechanisms mediating asbestos-induced cell proliferation and fibrogenesis, we studied mice exposed to chrysotile asbestos for five hours. The mice were normal (strain B10.D2/nSn)(C5+) and a congenic strain (B10.D2/oSn), deficient in the fifth component of complement (C5-). We knew that the latter exhibit a depressed asbestos-induced macrophage response and wanted to learn whether the depressed response correlated with measurements of cell proliferation and progression of an interstitial lesion. Sections of first alveolar duct bifurcations were prepared for light microscopic autoradiography and ultrastructural morphometry at varying times after animal exposure to asbestos. In sham-exposed C5+ and C5- animals, less than 1% of epithelial and interstitial cells of the terminal bronchioles and alveolar ducts incorporated tritiated thymidine (3H-TdR) at any time after exposure to asbestos. Between 19 and 72 hours after exposure, epithelial and interstitial cells in both strains of mice exhibited significantly increased levels of 3H-TdR incorporation. The response decreased by eight days postexposure, and 3H-TdR incorporation was normal one month after exposure. Similarly, morphometry showed that both the C5+ and C5- asbestos-exposed mice exhibited significant increases in the volume density of epithelial and interstitial cells 48 hours after exposure. However, one month after exposure, the normal C5+ asbestos-exposed mice developed a fibrotic lesion, whereas the C5- asbestos-exposed animals were no different from sham-exposed C5- controls. The depressed macrophage response in the C5- animals does not appear to change the early mitogenic response to asbestos but may be central to the apparent attenuation of fibrogenesis.

Chrysotile asbestos inhalation induces tritiated thymidine incorporation by epithelial cells of distal bronchioles.

Previous studies in a rat model of asbestosis have demonstrated increased incorporation of tritiated thymidine by bronchiolar and alveolar epithelial cells 19 to 72 h after a single, 5-h exposure to chrysotile asbestos. This increase in thymidine labeling occurred at the first alveolar duct bifurcations, where terminal bronchioles end and where asbestos deposition is most concentrated. To determine whether airways more proximal than the terminal bronchioles exhibit a similar type of proliferative response to asbestos, incorporation of tritiated thymidine by airway epithelial cells was determined by light microscopic autoradiography. Incorporation by the epithelium in regions of the trachea, mainstem bronchi, and bronchioles was measured in lung tissue from sham-exposed and chrysotile asbestos-exposed rats, zero and 33 h after exposure. Sham-exposed animals and those studied immediately after exposure exhibited no increases in tritiated thymidine incorporation at any airway level. Tritiated thymidine incorporation by epithelial cells of bronchioles in peripheral regions of the lungs was significantly increased, as much as 20-fold, 33 h after chrysotile exposure. In the same asbestos-exposed animals, epithelial cells of the trachea, the bronchi, and the larger bronchioles did not exhibit increased cell labeling. The fact that asbestos was deposited throughout all airway levels, yet increased thymidine incorporation is observed primarily in the peripheral bronchiolar regions, raises interesting questions regarding the mechanisms of asbestos-induced cell proliferation.

Brief inhalation of chrysotile asbestos induces rapid proliferation of bronchiolar-alveolar epithelial and interstitial cells.

Inhalation of asbestos fibres causes a progressive interstitial pulmonary fibrosis. To understand the basic cellular mechanisms which lead to this disease, we have studied the earliest proliferative events at the bronchiolar-alveolar regions of rats and mice exposed to chrysotile asbestos for 5 h. Animals were injected with tritiated thymidine 4 h prior to sacrifice at varying times ranging from immediately after cessation of exposure to one month post exposure. Light microscopic autoradiography showed that air-exposed control animals never had more than 1% of cells labelled. Rats and mice studied immediately after exposure also had normal numbers of labelled cells. However, between 12 and 48 h post exposure, asbestos-exposed animals exhibited up to 4-fold increases in the percentages of labelled epithelial and interstitial cells. Normal labelling returned by 8 days after exposure and was maintained through the one-month period studied. We conclude that inhalation of chrysotile asbestos induces rapid and highly significant increases in proliferation of epithelial and interstitial cells of the bronchiolar-alveolar regions where asbestos fibres were initially deposited.