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.

A novel synthetic erionite fibre radiolabelled with (57)Co.

The aim was to produce a radiolabelled fibre suitable for long-term carcinogenesis studies. To this end, we have successfully synthesised erionite fibres by a method adapted to incorporate (57)Co into the crystal framework. Morphologically the fibres are straight, of median length 2.5 microm, with 11% of fibres > 8 microm long, and median width 0.32 microm. These values are comparable to natural Oregon erionite. Autoradiography confirmed that the (57)Co was associated with the fibres themselves. The stability of the radiolabel in vivo was examined by instilling 1 mg of synthetic erionite into the lungs of F-344 rats. About half of the thoracic content of (57)Co was cleared in the first week, and over the following 5 weeks the remainder was cleared slowly with a half-time of 120 days. After 6 weeks the urinary excretion of (57)Co was only 0.054% of the initial lung content per day. This represented fibre dissolution plus any leaching of (57)Co from the fibres. It can be concluded that the (57)Co is bound into the erionite fibres with sufficient stability in vivo for studying their effects in relation to translocation to the pleura.

Radon emanation from NORM-contaminated pipe scale and soil at petroleum industry sites.

Radon-222 emanation fractions were determined for barite scale deposits associated with petroleum production tubing and soil contaminated with naturally occurring radioactive material (NORM). Samples were analyzed for 226Ra concentration, the results of which were used to calculate the 222Rn emanation fraction for the sample. An important parameter determining the overall Rn activity flux from a solid medium, 222Rn emanation fraction represents the fraction of 222Rn produced that enters the interconnected pore space within a medium contaminated with 226Ra before the 222Rn undergoes radioactive decay. The primary objective of the study was to determine whether 222Rn emanation fractions from pipe scale and soil from petroleum production sites are similar to those of uranium mill tailings. Pipe scale samples were collected at four sites representing a wide geographical area, and consisted primarily of barite scale where Ra atoms have replaced a fraction of the Ba within the crystal lattice of the scale. Soil samples were collected at five sites, from areas exhibiting elevated surface gamma exposure rates indicating the presence of NORM. For comparison, 226Ra concentrations and 222Rn emanation fraction were also determined for uranium mill tailings samples provided from a site in Utah. Although 2226Ra concentrations from pipe scale samples were similar to those found in uranium mill tailings, 222Rn emanation fractions from scale were generally lower. Emanation fractions from each data set were statistically different from those of mill tailings (p < or = 0.01). The differences are probably due to physical differences between the two media and to the method by which the Ra is deposited in the material. Radon emanation from soils was extremely variable owing not only to differences in physical and chemical soil properties, but also to the means by which NORM has entered the soil. Although additional emanation measurements from other sites are needed, the data collected at these sites indicate that regulations intended to protect human health from 222Rn inhalation should consider the type and properties of the medium in which the NORM is contained, rather than relying strictly on concentrations of the parent 226Ra.

Design, synthesis and testing of amino-bicycloaryl based orally bioavailable thrombin inhibitors.

Replacement of the highly basic benzamidine moiety with moderate basic amino-bicycloaryl moieties in a series of thrombin inhibitors related to NAPAMP provided potent enzyme inhibition and significant improvements in membrane transport and oral bioavailability.

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.

1-Aminoisoquinoline as benzamidine isoster in the design and synthesis of orally active thrombin inhibitors.

Replacement of the highly basic benzamidine moiety of NAPAP by the moderately basic 1-aminoisoquinoline moiety resulted in thrombin inhibitors with improved selectivity towards trypsin and enhanced Caco-2 cell permeability.

Evaluation of atmospheric transport models for use in phase II of the historical public exposures studies at the Rocky Flats Plant.

Five atmospheric transport models were evaluated for use in Phase II of the Historical Public Exposures Studies at the Rocky Flats Plant. Models included a simple straight-line Gaussian plume model (ISCST2), several integrated puff models (RATCHET, TRIAD, and INPUFF2), and a complex terrain model (TRAC). Evaluations were based on how well model predictions compared with sulfur hexafluoride tracer measurements taken in the vicinity of Rocky Flats in February 1991. Twelve separate tracer experiments were conducted, each lasting 9 hr and measured at 140 samplers in arcs 8 and 16 km from the release point at Rocky Flats. Four modeling objectives were defined based on the endpoints of the overall study: (1) the unpaired maximum hourly average concentration, (2) paired time-averaged concentration, (3) unpaired time-averaged concentration, and (4) arc-integrated concentration. Performance measures were used to evaluate models and focused on the geometric mean and standard deviation of the predicted-to-observed ratio and the correlation coefficient between predicted and observed concentrations. No one model consistently outperformed the others in all modeling objectives and performance measures. About 75% of the maximum hourly concentration predictions were within a factor of 5 of the observations. About 64% of the paired and 80% of the unpaired time-averaged model predictions were within a factor of 5 of the observations. The overall performance of the RATCHET model was somewhat better than the other models. All models appeared to experience difficulty defining plume trajectories, which was attributed to the influence of multilayered flow initiated by terrain complexities and the diurnal flow patterns characteristic of the Colorado Front Range.

Measurement of 222Rn flux, 222Rn emanation, and 226,228Ra concentration from injection well pipe scale.

222Rn flux (Bq s(-1)) was measured from the ends of twenty sections of produced water injection tubing (pipe) containing barite scale contaminated with naturally occurring radioactive material. Exposure measurements near the pipes were as high as 77.4 nC kg(-1)h(-1) (300 microR h(-1)). Flux measurements were accomplished by first purging the pipes with dry nitrogen and then collecting the outflow (nitrogen and radon) on charcoal columns affixed to the end of the pipe for 66 hours. As determined in this manner, 222Rn flux from the ends of the pipe ranged from 0.017 to 0.10 Bq s(-1) (0.46 to 2.7 pCi s(-1)). Following the radon flux measurements, pipe scale was removed and a representative sample was taken for 226Ra and 228Ra concentration measurements and determination of 222Rn emanation fractions (the fraction of the total radon contained in a material that is released from the material and free to migrate). The samples were also analyzed for gross mineral content. Emanation fraction measurements for 222Rn ranged from 0.020 to 0.063, while 226Ra concentrations ranged from 15.7 to 102 Bq g(-1) (424 to 2,760 pCi g(-1)). Barite was the predominate mineral in 17 of the 20 scale samples collected. Much of the previous work dealing with radon emanation fraction measurements has involved uranium mill tailings. Compared to mill tailings and natural soils which have emanation fractions that typically range from 0.1 to 0.3, the emanation fractions measured for these NORM scales are substantially lower.

Feasible synthesis and biological properties of six 'non-glycosamino' glycan analogues of the antithrombin III binding heparin pentasaccharide.

In this paper, we report the synthesis of 'non-glycosamino' glycan analogues 5-10 of the antithrombin III binding pentasaccharide 1. Pentasaccharides 5-10 feature a pseudo-alternating EFGH tetrasaccharide sequence, that is, the disaccharide fragments EF and GH have the same substitution pattern. In the synthetic strategy applied for the synthesis of pentasaccharides 5-10, the properly protected EF disaccharide fragments 19 and 20 are obtained from their GH counterparts 17 and 18 by base-catalyzed epimerization. Series I, comprising pentasaccharides 5-7, has an invariable EFGH tetrasaccharide containing 2-O-sulfate 3-O-methyl uronic acid moieties. Series II, on the other hand, contains pentasaccharides 8-10 and has an invariable EFGH tetrasaccharide containing 2,3-di-O-methyl uronic acid moieties. Coupling disaccharides 17 with 25 and 18 with 26 exclusively afforded the alpha-coupled tetrasaccharides 27 and 28, respectively. Glycosylation of acceptor tetrasaccharides 29 and 30 with glucosyl donors 35, 36 and 39 provided, after deprotection and sulfation, the title-compounds 5-10. Biological data obtained with series I and II indicate that the in vivo half-life but not the intrinsic anti-Xa activity depends on the substitution pattern of the D-unit. In addition, the applicability of reversed UV capillary electrophoresis as an analytical tool to determine the purity of these 'non-glycosamino' glycans is demonstrated.

COMIDA: a radionuclide food chain model for acute fallout deposition.

A dynamic food chain model and computer code, named "COMIDA," has been developed to estimate radionuclide concentrations in agricultural food products following an acute fallout event. COMIDA estimates yearly harvest concentrations for five human crop types (Bq kg-1 crop per Bq m-2 deposited) and integrated concentrations for four animal products (Bq d kg-1 animal product per Bq m-2) for a unit deposition that occurs on any user-specified day of the year. COMIDA is structurally very similar to the PATHWAY model and includes the same seasonal transport processes and discrete events for soil and vegetation compartments. Animal product assimilation is modeled using simpler equilibrium models. Differential transport and ingrowth of up to three radioactive progeny are also evaluated. Benchmark results between COMIDA and PATHWAY for monthly fallout events show very similar seasonal agreement for integrated concentrations in milk and beef. Benchmark results between COMIDA and four international steady-state models show good agreement for deposition events that occur during the middle of the growing season. COMIDA will be implemented in the new Department of Energy version of the MELCOR Accident Consequence Code System for evaluation of accidental releases from nuclear power plants.

The effects of heating and devitrification on the structure and biological activity of aluminosilicate refractory ceramic fibres.

Three grades of ceramic fibre have been examined for their composition, structures and biological effect in several in vitro assay systems. The fibres were examined in the 'as-manufactured' state and after heating at 1200 and 1400 degrees C. Devitrification of the fibres at 1200 degrees C probably gave mullite crystals on the surface and caused the formation of the high-temperature form of cristobalite and, in zirconia grade fibres, the high-temperature, tetragonal form of zirconia as well. Further heating changed surface structure and led to zircon production in the zirconia fibres. Heating reduced the affinity of the fibres for the surface of V79-4 cells and lowered fibre toxicity toward these cells and towards macrophage-like cells. These changes in toxicity were not due to a reduction in the fibrous nature of the materials although they did become more brittle and powders prepared from them contained more isometric particles than those from as-manufactured materials. This suggests that the devitrification occurring during the use of these materials in high-temperature environments will not necessarily enhance their adverse biological activities despite the production of one phase of crystalline silica.

Fibrous dust release from asbestos substitutes in friction products.

A small-scale study was carried out on friction and reinforcing materials containing Kevlar and glass fibres. Kevlar, an aramid fibre, and synthetic silicate fibres are being increasingly used in brake pads and shoes for cars and trucks. The fibre levels given out under abrasion in the laboratory were low. As a comparison, a brake pad containing asbestos was also tested and gave high levels of airborne fibres.

Year-to-year variations in annual average indoor 222Rn concentrations.

Annual average indoor 222Rn concentrations in 40 residences in and around Grand Junction, CO, have been measured repeatedly since 1984 using commercial alpha-track monitors (ATM) deployed for successive 12-mo time periods. Data obtained provide a quantitative measure of the year-to-year variations in the annual average Rn concentrations in these structures over this 6-y period. A mean coefficient of variation of 25% was observed for the year-to-year variability of the measurements at 25 sampling stations for which complete data were available. Individual coefficients of variation at the various stations ranged from a low of 7.7% to a high of 51%. The observed mean coefficient of variation includes contributions due to the variability in detector response as well as the true year-to-year variation in the annual average Rn concentrations. Factoring out the contributions from the measured variability in the response of the detectors used, the actual year-to-year variability of the annual average Rn concentrations was approximately 22%.

Modification of fibrous Oregon erionite and its effects on in vitro activity.

A sample of erionite, a fibrous zeolite, was modified by milling to reduce the number and length of the fibres and by extraction with cyclohexane. The in vitro activities of this mineral were found to depend on the presence of long fibres. The erionite contained fewer of these fibres than the UICC asbestos samples but, unlike these materials, erionite can cause the transformation of C3H 10T1/2 cells. Erionite did not increase the activities of benzo[a]pyrene in this cell transformation assay. The cytotoxic activities of both asbestos and erionite have a similar dependence on the number of long fibres. Extraction with cyclohexane did not affect the activity of erionite.

Airborne asbestos fibre levels in buildings: a summary of UK measurements.

The UK Health and Safety Executive, in conjunction with the Department of the Environment, has carried out a number of surveys of airborne asbestos fibre concentrations in buildings. All samples have been collected on membrane filters and analysed by analytical transmission electron microscopy. Four categories of buildings under normal occupation have been investigated; non-domestic buildings containing sprayed or trowelled asbestos, domestic buildings containing sprayed asbestos or asbestos plaster, buildings with warm air heaters containing asbestos and buildings without asbestos materials. A number of buildings have also been surveyed during and after the removal of asbestos materials. The choice of measurement indices and analytical procedures is reviewed, before measurements are compared in terms of the concentration of asbestos fibres greater than 5 microns long. The decision whether to remove asbestos from occupied buildings is discussed with reference to the associated cost and risk. In the present survey, management of undamaged asbestos appeared preferable to large-scale removal.

Levels of airborne man-made mineral fibres in dwellings in the UK: results of a preliminary survey.

Levels of airborne man-made mineral fibres (MMMF) were measured during the insulation of lofts and after the disturbance of the insulation wools. Transmission electron microscopy was used for the analysis. Generally, the personal samples showed fibre levels of up to 0.7 f/ml, whereas static samples showed fibre levels of 0.05 f/ml in the lofts. Little contamination of living space occurred during these operations.

The in vitro activities of a highly carcinogenic mineral fibre--potassium octatitanate.

The in vitro activities of a highly carcinogenic potassium octatitanate fibre (Fybex) have been investigated. This material caused a low level of in vitro transformation in C3H10T1/2 cells and is thus more active in this assay than the UICC amphibole asbestos samples but less active than fibrous erionite. This ranking is in accord with carcinogenicity in vivo. However Fybex had no detectable activity in an assay for DNA damage based on the S1-nuclease sensitivity of the DNA from exposed cells. In that assay crocidolite asbestos was more active than either of the more carcinogenic dusts. It is suggested that the activities of amphibole asbestos in assays for genetic toxicity may depend on the production of free radicals via a catalytic reaction requiring the presence of transition elements which are either not present or only present at low concentrations in erionite or Fybex. This type of reaction may not be related to in vivo carcinogenicity. The action of fibrous dusts against macrophage-like cells, measured in this instance by the release of arachidonic acid, remains one of the best measures of biological activity.

Size distributions of airborne superfine man-made mineral fibers determined by transmission electron microscopy.

A survey was conducted to determine the size distribution of airborne man-made mineral fibers in three factories using bulk materials which contain many fibers with diameters less than 0.3 micrometers. Personal samples were taken in two of the factories visited. In all the cases a full length and diameter distribution, determined by transmission electron microscopy, are presented. Median diameters ranged from 0.1 to 0.3 micrometers and, as a result, a substantial proportion of the fibers would not be detected using light microscopy or scanning electron microscopy even for fibers longer than 5 micrometers.