Libby Amphibole Asbestos Research Articles

Asbestos-induced autoantibodies across Libby demographics

Asbestos-induced autoantibodies across Libby demographics Aiden Niblett, Jean Pfau, and Kinta Serve focus on asbestos-induced autoantibodies across different demographics in Libby. They emphasize the importance of understanding the impact of asbestos. Asbestos is a naturally occurring fibrous silicate mineral that has been used in construction due to its tensile strength and heat resistance. However, its small size and rigid shape allow it to enter deep into the respiratory tract upon inhalation, and exposures have been linked to serious lung diseases like pulmonary fibrosis and cancers. (1) The town of Libby, Montana, has a history of asbestos exposure due to a local vermiculite mine that operated from 1920-1990. Vermiculite mined from Libby and sold in products such as Zonolite Attic Insulation was found to be contaminated with Libby Amphibole (LA) asbestos, a unique mix of tremolite, winchite, and richterite fibers that is associated with severe lung diseases. (2)

Lung cancer screening in patients with Libby amphibole disease: High yield despite predominantly environmental and household exposure.

BackgroundLung cancer screening with low‐dose computed tomography (CT) scanning (LDCT) is accepted as a screening tool, but its application to populations exposed to recognized occupational or environmental carcinogens is limited. We apply LDCT to a population with a predominantly nonoccupational exposure to a recognized human lung carcinogen, Libby amphibole asbestos (LA).MethodsPatients in an asbestos disease clinic in Libby, Montana who were aged 50 to 84 years, greater than or equal to 20 pack‐year history of tobacco use (irrespective of quit date), and asbestos‐related pleuropulmonary disease on high‐resolution CT scan were offered free annual lung cancer screening over a 39‐month period.ResultsOf 2897 clinic patients, 1149 (39.7%) met eligibility criteria, and 567 (49%) were screened with 1014 low‐dose CT scans. Most screened patients had principally environmental (333 or 59%) or household exposure (145 or 25%) to LA. Seventeen primary lung cancers were identified, mostly in early stages: 10 at stage 1, two at stage 2, three at stages 3 to 4, and two at limited small‐cell cancers. The screening yield was 1.9 at baseline scan and 1.5% on the first annual scan.ConclusionsConsistent with the guidelines of the National Comprehensive Cancer Network and American Association of Thoracic Surgery, LDCT for early lung cancer detection should be offered to people with significant exposure to occupational or environmental human lung carcinogens.

Six Years of Asbestos Health Screening Results in Libby, Montana

SESSION TITLE: Environmental and Occupational Health SESSION TYPE: Original Investigation Poster PRESENTED ON: Wednesday, November 1, 2017 at 01:30 PM - 02:30 PM PURPOSE: Libby, Montana in 2009 became the first and only EPA-declared public health emergency which led to Affordable Care Act (ACA) funding for free asbestos health screening. Libby was the site of a vermiculite mine that operated between 1919 and 1990. The vermiculite was contaminated with fibers called Libby amphibole (LA) asbestos. The Center for Asbestos Related Disease (CARD) has been conducting screening under the ACA since July 2011. Results from these free asbestos health screenings will be presented. METHODS: Free screenings include exposure history, health history, respiratory symptoms, and tobacco use history, a spirometry and PA CXR, and a medical provider visit. In many instances, a chest CT without contrast for confirmation of asbestos related abnormalities is also ordered. Smoking cessation and fecal occult blood testing are also offered. Eligibility for screening requires individuals to have lived, worked or played in the Libby, MT area for at least 6 months at least 10 years prior to being screened to target those with sufficient exposure and latency. Once asbestos related abnormalities are identified on CT, individuals are considered diagnosed and no longer eligible for screening. CXRs are sent for B reading and CT scans are sent to be read by thoracic radiologists with expertise in identification of asbestos related abnormalities. RESULTS: 4,466 B reads were returned and asbestos related abnormalities were identified on 431 of them (9.7%). 3,192 radiologist’s CT reads were returned and asbestos related abnormalities were identified on 1,204 of them (37.7%). Based on positive CT reads, 27% of screenings were considered positive for ARPD. Of the 27% (1,204 of 4,466), 441 had abnormal spirometry, 273 were current smokers, and 974 reported respiratory symptoms such as chronic cough and dyspnea on exertion. In addition 10 lung masses were identified in the screening population. The vast majority of individuals who underwent screening reported no occupational exposed to LA. CONCLUSIONS: Ongoing screening in Libby, MT along with EPA cleanup of the Libby asbestos superfund site has been ongoing since 2000 and continues today. Identification of asbestos related abnormalities in this population continues with 27% of the screenings resulting in identification of asbestos related abnormalities in last 6 years. Most reported exposures are nonoccupational in this population. CLINICAL IMPLICATIONS: LA exposure may be occurring nationwide due to attic insulation in millions of homes. DISCLOSURE: The following authors have nothing to disclose: Tracy McNew, Charles Black No Product/Research Disclosure Information

Comparative health effects in mice of Libby amphibole asbestos and a fibrous amphibole from Arizona

This project developed from studies demonstrating that Libby Amphibole Asbestos (LAA) causes a non-typical set of health outcomes not generally reported for asbestos, including systemic autoimmunity and an unusual and devastating lamellar pleural thickening that progresses to severe pulmonary dysfunction and death. Further, mineral fiber mixtures with some similarities to LAA have recently been discovered in southern Nevada and northwestern Arizona, where the material exists in extensive recreational areas and is present in yards, roads, parking lots and school yards. The objective was to compare the health outcomes in mice exposed to either LAA or the fibrous amphiboles collected in Arizona at the Lake Mead National Recreational Area at very low doses to represent environmental exposures. In this study, the fibrous amphibole asbestos sample from Arizona (AzA) is composed of winchite (69%), actinolite (22%), and non-amphibole minerals (9%) and has a mean aspect ratio of 16.7±0.9. Fibrous amphibole asbestos from Libby (LAA) is composed of winchite (70%), richterite (9%), tremolite (5%), and non-amphibole minerals (16%) with a mean aspect ratio of 8.4±0.7. C57BL/6 mice were exposed by oropharyngeal aspiration to fiber suspensions at a very low dose of 3μg/mouse. After seven months, both LAA- and AzA-exposed mice had indices of chronic immune dysfunction related to a TH17 cytokine profile, with B cell activation, autoantibody production and proteinuria, suggesting kidney involvement. In addition, both exposures led to significant lung and pleural fibrosis. These data suggest that there is risk of pulmonary disease and autoimmune outcomes with environmental exposure to amphibole asbestos, and that this is not limited to Libby, Montana.

Childhood exposure to Libby amphibole asbestos and respiratory health in young adults

ObjectivesVermiculite ore containing Libby amphibole asbestos (LAA) was mined in Libby, MT, from the 1920s-1990. Recreational and residential areas in Libby were contaminated with LAA. This objective of this study was to characterize childhood exposure to LAA and investigate its association with respiratory health during young adulthood. MethodsYoung adults who resided in Libby prior to age 18 completed a health and activity questionnaire, pulmonary function testing, chest x-ray and HRCT scan. LAA exposure was estimated based on participant report of engaging in activities with potential LAA exposure. Quantitative LAA estimates for activities were derived from sampling data and literature reports. ResultsA total of 312 participants (mean age 25.1 years) were enrolled and reported respiratory symptoms in the past 12 months including pleuritic chest pain (23%), regular cough (17%), shortness of breath (18%), and wheezing or whistling in the chest (18%). Cumulative LAA exposure was significantly associated with shortness of breath (aOR = 1.12, 95% CI 1.01–1.25 per doubling of exposure). Engaging in recreational activities near Rainy Creek Road (near the former mine site) and the number of instances heating vermiculite ore to make it expand or pop were also significantly associated with respiratory symptoms. LAA exposure was not associated with pulmonary function or pleural or interstitial changes on either chest x-ray or HRCT. ConclusionsPleural or interstitial changes on x-ray or HRCT were not observed among this cohort of young adults. However, childhood exposure to LAA was significantly associated with respiratory symptoms during young adulthood. Pleuritic chest pain, in particular, has been identified as an early symptom associated with LAA exposure and therefore warrants continued follow-up given findings of progressive disease in other LAA exposed populations.

Pleural plaques and lung function in the Marysville worker cohort: a re-analysis

Background: In the 2014 Integrated Risk Information System (IRIS) assessment for Libby amphibole asbestos (LAA), US EPA calculated a reference concentration (RfC) based on the prevalence of pleural plaques in a group of vermiculite workers in Marysville, Ohio. This RfC is based on the assumption that pleural plaques are associated with adverse lung function. In this study, we evaluated the association between pleural plaques and lung function in the Marysville worker cohort to determine whether they are associated with adverse effects or, rather, are more likely a biomarker of cumulative exposure to LAA.Methods: We obtained the dataset on the Marysville worker cohort from University of Cincinnati, which included information on demographics, occupational exposures and results of chest high-resolution computed tomography (HRCT)/computed tomography (CT) scans and pulmonary function tests (PFTs). We used multivariate linear regression to estimate mean differences in several lung function parameters, and logistic regression to evaluate the odds of abnormal ventilatory patterns, among men with different pulmonary findings on HRCT/CT scans.Results: No statistically significant differences in FEV1, FVC, FEV1/FVC, TLC, RV or DLCO were observed between workers with normal scans and those with pleural plaques but no other abnormalities. In contrast, workers with other abnormal findings had statistically significant lower FEV1, FVC, TLC and DLCO, compared with those with normal scans.Conclusions: This study does not indicate that pleural plaques have a significant effect on lung function when past asbestos exposure is accounted for.

Libby amphibole-induced mesothelial cell autoantibodies bind to surface plasminogen and alter collagen matrix remodeling.

Lamellar pleural thickening (LPT) is a fibrotic disease induced by exposure to Libby amphibole (LA) asbestos that causes widespread scarring around the lung, resulting in deterioration of pulmonary function. Investigating the effects of autoantibodies to mesothelial cells (MCAA) present in the study populations has been a major part of the effort to understand the mechanism of pathogenesis. It has been shown in vitro that human mesothelial cells (Met5a) exposed to MCAA increase collagen deposition into the extracellular matrix (ECM). In this study, we sought to further elucidate how MCAA drive increased collagen deposition by identifying the protein targets bound by MCAA on the cellular surface using biotinylation to label and isolate surface proteins. Isolated surface protein fractions were identified as containing MCAA targets using ELISA. The fractions that demonstrated binding by MCAA were then analyzed by tandem mass spectrometry (MS/MS) and MASCOT analysis. The most promising result from the MASCOT analysis, plasminogen (PLG), was tested for MCAA binding using purified human PLG in an ELISA. We report that serum containing MCAA bound at an optical density (OD) 3 times greater than that of controls, and LA‐exposed subjects had a high frequency of positive tests for anti‐PLG autoantibodies. This work implicates the involvement of the plasminogen/plasmin system in the mechanism of excess collagen deposition in Met5a cells exposed to MCAA. Elucidating this mechanism could contribute to the understanding of LPT.

Persistent effects of Libby amphibole and amosite asbestos following subchronic inhalation in rats.

BackgroundHuman exposure to Libby amphibole (LA) asbestos increases risk of lung cancer, mesothelioma, and non-malignant respiratory disease. This study evaluated potency and time-course effects of LA and positive control amosite (AM) asbestos fibers in male F344 rats following nose-only inhalation exposure.MethodsRats were exposed to air, LA (0.5, 3.5, or 25.0 mg/m3 targets), or AM (3.5 mg/m3 target) for 10 days and assessed for markers of lung inflammation, injury, and cell proliferation. Short-term results guided concentration levels for a stop-exposure study in which rats were exposed to air, LA (1.0, 3.3, or 10.0 mg/m3), or AM (3.3 mg/m3) 6 h/day, 5 days/week for 13 weeks, and assessed 1 day, 1, 3, and 18 months post-exposure. Fibers were relatively short; for 10 mg/m3 LA, mean length of all structures was 3.7 μm and 1 % were longer than 20 μm.ResultsTen days exposure to 25.0 mg/m3 LA resulted in significantly increased lung inflammation, fibrosis, bronchiolar epithelial cell proliferation and hyperplasia, and inflammatory cytokine gene expression compared to air. Exposure to 3.5 mg/m3 LA resulted in modestly higher markers of acute lung injury and inflammation compared to AM. Following 13 weeks exposure, lung fiber burdens correlated with exposure mass concentrations, declining gradually over 18 months. LA (3.3 and 10.0 mg/m3) and AM produced significantly higher bronchoalveolar lavage markers of inflammation and lung tissue cytokines, Akt, and MAPK/ERK pathway components compared to air control from 1 day to 3 months post-exposure. Histopathology showed alveolar inflammation and interstitial fibrosis in all fiber-exposed groups up to 18 months post-exposure. Positive dose trends for incidence of alveolar epithelial hyperplasia and bronchiolar/alveolar adenoma or carcinoma were observed among LA groups.ConclusionsInhalation of relatively short LA fibers produced inflammatory, fibrogenic, and tumorigenic effects in rats which replicate essential attributes of asbestos-related disease in exposed humans. Fiber burden, inflammation, and activation of growth factor pathways may persist and contribute to lung tumorigenesis long after initial LA exposure. Fiber burden data are being used to develop a dosimetry model for LA fibers, which may provide insights on mode of action for hazard assessment.Electronic supplementary materialThe online version of this article (doi:10.1186/s12989-016-0130-z) contains supplementary material, which is available to authorized users.

Exposure-response modeling of non-cancer effects in humans exposed to Libby Amphibole Asbestos; update

The United States Environmental Protection Agency (EPA) developed a quantitative exposure-response model for the non-cancer effects of Libby Amphibole Asbestos (LAA) (EPA, 2014). The model is based on the prevalence of localized pleural thickening (LPT) in workers exposed to LAA at a workplace in Marysville, Ohio (Lockey et al., 1984; Rohs et al., 2008). Recently, Lockey et al. (2015a) published a follow-up study of surviving Marysville workers. The data from this study increases the number of cases of LPT and extends the observation period for a number of workers, thereby providing a strengthened data set to define and constrain the optimal exposure-response model for non-cancer effects from inhalation exposure to LAA. The new data were combined with the previous data to update the exposure-response modeling for LPT. The results indicate that a bivariate model using cumulative exposure and time since first exposure is appropriate, and the benchmark concentration is similar to the findings previously reported by EPA (2014). In addition, the data were also used to develop initial exposure-response models for diffuse pleural thickening (DPT) and small interstitial opacities (SIO).

Analyzing The Effect Of Exposure Misclassification And Alternative Asbestos Exposure Metrics On The Risk Of Worker Mortality From Asbestosis

Background: In Libby, MT, the mining of asbestos-contaminated vermiculite ore exposed workers and residents to asbestos fibers. The mine closed in 1990. Libby vermiculite was used in attic insulation and as a soil conditioner. USEPA recently completed its Toxicological Review of Libby Amphibole asbestos (LAA) including toxicity values for cancer and pleural thickening. The work described here evaluated risks of asbestosis mortality. Methods: The main analysis was based on 880 Libby workers hired when higher quality exposure data were available. Cox models were used to assess the effects of LAA on asbestosis mortality. Sensitivity analyses included four lags for asbestosis latency and multiple exposure metrics including cumulative exposure, residence-time weighted exposure, and metrics allowing for fiber clearance. Results were compared using AIC weights which assign probabilities of each model being the best fit. Results: Models that contained 15-year lags and allowed for simulated fiber clearance over time were the best fitting for asbestosis mortality (p

Asbestos-induced pulmonary fibrosis is augmented in 8-oxoguanine DNA glycosylase knockout mice.

Asbestos causes asbestosis and malignancies by mechanisms that are not fully established. Alveolar epithelial cell (AEC) injury and repair are crucial determinants of the fibrogenic potential of noxious agents such as asbestos. We previously showed that mitochondrial reactive oxygen species mediate asbestos-induced AEC intrinsic apoptosis and that mitochondrial human 8-oxoguanine-DNA glycosylase 1 (OGG1), a DNA repair enzyme, prevents oxidant-induced AEC apoptosis. We reasoned that OGG1 deficiency augments asbestos-induced pulmonary fibrosis. Compared with intratracheal instillation of PBS (50 μl) or titanium dioxide (100 μg/50 μl), crocidolite or Libby amphibole asbestos (100 μg/50 μl) each augmented pulmonary fibrosis in wild-type C57BL/6J (WT) mice after 3 weeks as assessed by histology, fibrosis score, lung collagen via Sircol, and type 1 collagen expression; these effects persisted at 2 months. Compared with WT mice, Ogg1 homozygous knockout (Ogg1(-/-)) mice exhibit increased pulmonary fibrosis after crocidolite exposure and apoptosis in cells at the bronchoalveolar duct junctions as assessed via cleaved caspase-3 immunostaining. AEC involvement was verified by colocalization studies using surfactant protein C. Asbestos increased endoplasmic reticulum stress in the lungs of WT and Ogg1(-/-) mice. Compared with WT, alveolar type 2 cells isolated from Ogg1(-/-) mice have increased mtDNA damage, reduced mitochondrial aconitase expression, and increased P53 and cleaved caspase-9 expression, and these changes were enhanced 3 weeks after crocidolite exposure. These findings suggest an important role for AEC mtDNA integrity maintained by OGG1 in the pathogenesis of pulmonary fibrosis that may represent a novel therapeutic target.

HRCT/CT and associated spirometric effects of low Libby amphibole asbestos exposure.

Evaluate the relationship between cumulative fiber exposure and high-resolution or conventional chest computed tomography (HRCT/CT) changes and spirometry of workers with Libby amphibole asbestos exposure. Of the original 1980 cohort (n = 513), 431 were living and asked to participate. Images were evaluated for localized pleural thickening (LPT), diffuse pleural thickening (DPT), and parenchymal changes. A total of 306 participants provided either HRCT/CT scans (n = 191) or chest radiographs (n = 115). Of the 191 with HRCT/CT, 52.9% had pleural changes and 13.1% had parenchymal changes. Those with LPT only, LPT and/or DPT, or DPT and/or parenchymal changes had mean 6.1, 8.0, and 18.0 loss in percent predicted forced vital capacity, respectively. Exposure to vermiculite containing amphibole fibers is associated with pleural and parenchymal HRCT/CT changes at low cumulative fiber exposure; these changes are associated with spirometric decrements.

Comparative Long-Term Toxicity of Libby Amphibole and Amosite Asbestos in Rats After Single or Multiple Intratracheal Exposures

In former mine workers of Libby, MT, exposure to amphibole-containing vermiculite was linked to increased rates of asbestosis, lung cancer, and mesothelioma. Although many studies showed adverse effects following exposure to Libby amphibole (LA; a mixture of winchite, richterite, and tremolite), little is known regarding the relative toxicity of LA compared to regulated asbestos, or regarding the risks associated with acute high-dose exposures relative to repeated low-dose exposures. In this study, pulmonary function, inflammation, and pathology were assessed after single or multiple intratracheal (IT) exposures of LA or a well-characterized amosite (AM) control fiber with equivalent fiber characteristics. Male F344 rats were exposed to an equivalent total mass dose (0.15, 0.5, 1.5, or 5 mg/rat) of LA or AM administered either as a single IT instillation, or as multiple IT instillations given every other week over a 13-wk period, and necropsied up to 20 mo after the initial IT. When comparing the two fiber types, in both studies LA resulted in greater acute neutrophilic inflammation and cellular toxicity than equal doses of AM, but long-term histopathological changes were approximately equivalent between fibers, suggesting that LA is at least as toxic as AM. In addition, although no dose-response relationship was discerned, mesothelioma or lung carcinomas were found after exposure to low and high dose levels of LA or AM in both studies. Conversely, when comparing studies, an equal mass dose given over multiple exposures instead of a single bolus resulted in greater chronic pathological changes in lung at lower doses, despite the initially weaker acute inflammatory response. Overall, these results suggest that there is a possibility of greater long-term pathological changes with repeated lower LA dose exposures, which more accurately simulates chronic environmental exposures.

Influence of exposure assessment and parameterization on exposure response. Aspects of epidemiologic cohort analysis using the Libby Amphibole asbestos worker cohort

Recent meta-analyses of occupational epidemiology studies identified two important exposure data quality factors in predicting summary effect measures for asbestos-associated lung cancer mortality risk: sufficiency of job history data and percent coverage of work history by measured exposures. The objective was to evaluate different exposure parameterizations suggested in the asbestos literature using the Libby, MT asbestos worker cohort and to evaluate influences of exposure measurement error caused by historically estimated exposure data on lung cancer risks. Focusing on workers hired after 1959, when job histories were well-known and occupational exposures were predominantly based on measured exposures (85% coverage), we found that cumulative exposure alone, and with allowance of exponential decay, fit lung cancer mortality data similarly. Residence-time-weighted metrics did not fit well. Compared with previous analyses based on the whole cohort of Libby workers hired after 1935, when job histories were less well-known and exposures less frequently measured (47% coverage), our analyses based on higher quality exposure data yielded an effect size as much as 3.6 times higher. Future occupational cohort studies should continue to refine retrospective exposure assessment methods, consider multiple exposure metrics, and explore new methods of maintaining statistical power while minimizing exposure measurement error.

Aspects of exposure measurement error in epidemiologic cohort analyses using the Libby amphibole asbestos worker cohort. Influence of changes in exposure assess

Background: The extent of employees’ work history covered by measured exposures has been shown, using meta-analysis, to be an important predictor of summary effect measures for lung cancer mortality risk associated with asbestos exposure. We studied lung cancers associated with exposures at the asbestos-contaminated vermiculite mine in Libby, Montana, a major supplier of vermiculite demand during the 20th century. The cohort of workers includes those hired after 1935 with mortality follow-up through 2006. The associated job exposure matrix is based on measured fiber exposures from 1968-1982. Prior to 1968, exposures were largely estimated based on extrapolation of job-specific exposures in the late 1960’s backwards in time to 1935 with an expert consideration of changes in workplace processes over time. Aims: To evaluate the influence of exposure measurement error on lung cancer potency estimates. Methods: We estimated the effect of occupational exposures on lung cancer mortality using the time-varying Cox regression model for different cohorts depending on worker’s dates of hire in order to gauge the impact of potential exposure measurement error over time. Supplemental analyses assessed the inclusion of the percentage of work-history covered by measured exposure as a time-varying covariate. Results: Compared to previous published analyses based on the cohort of workers hired after 1935, when exposures assignments from the job exposure matrix were based on measured exposures only 47% of the time, our analyses based on higher quality exposure data from workers hired after 1959, when occupational exposures were predominantly based on measured exposures (85%), yielded an effect size as much as 3.6 times higher. Conclusions: Future occupational cohort analyses should continue to refine retrospective exposure assessment methods and explore new methods to control for changes in the quality of exposure estimates over time. Disclaimer: This abstract does not necessarily reflect EPA policy.

Localized pleural thickening: Smoking and exposure to Libby vermiculite

There is limited research on the combined effects of smoking and asbestos exposure on risk of localized pleural thickening (LPT). This analysis uses data from the Marysville cohort of workers occupationally exposed to Libby amphibole asbestos (LAA). Workers were interviewed to obtain work and health history, including ever/never smoking and chest X-rays. Cumulative exposure estimates were developed on the basis of fiber measurements from the plant and work history. Benchmark concentration (BMC) methodology was used to evaluate the exposure-response relationship for exposure to LAA and a 10% increased risk of LPT, considering potential confounders and statistical model forms. There were 12 LPT cases among 118 workers in the selected study population. The mean exposure was 0.42 (SD=0.77) fibers/cc-year, and the prevalence of smoking history was 75.0% among cases and 51.9% among non-cases. When controlling for LAA exposure, smoking history was of borderline statistical significance (P-value=0.099), and its inclusion improved model fit, as measured by Akaike's Information Criterion. A comparison of BMC estimates was made to gauge the potential effect of smoking status. The BMC was 0.36 fibers/cc-year, overall. The BMC for non-smokers was approximately three times as high (1.02 fibers/cc-year) as that for the full cohort, whereas the BMC for smokers was about 1/2 that of the full cohort (0.17 fibers/cc-year).

Effects of Libby Amphibole Asbestos Exposure on Two Models of Arthritis in The Lewis Rat

Epidemiological data suggest that occupational exposure to the amphibole-containing vermiculite in Libby, MT, was associated with increased risk for developing autoimmune diseases and had an odds ratio of 3.23 for developing rheumatoid arthritis (RA). The collagen-induced arthritis (CIA) and the peptidoglycan-polysaccharide (PG-PS) models of RA were employed to determine whether exposure to Libby amphibole (LA) induced a more rapid onset, increased expression, or prolonged course of RA. Female Lewis rats were intratracheally instilled with total doses of 0.15, 0.5, 1.5, or 5 mg LA or 0.5 or 1.5 mg amosite asbestos, and arthritis was induced with either the PG-PS or CIA model. Neither LA nor amosite exposure affected the disease course in the CIA model, or the production of rheumatoid factor (RF) or anti-cyclic citrullinated peptide (CCP) antibodies. LA exposure reduced swelling in the PG-PS model and decreased anti-PG-PS and total immunoglobulin M (IgM) antibody titers. Both amosite and LA exposure increased the number of rats with circulating anti-nuclear antibodies (ANA), the majority of which presented a speckled staining pattern. However, this ANA enhancement was not dose responsive. These results failed to show a positive correlation between LA exposure and RA disease in two animal models, although upregulated ANA suggest an altered immunological profile consistent with other systemic autoimmune diseases.

Vascular and Thrombogenic Effects of Pulmonary Exposure to Libby Amphibole

Exposure to Libby amphibole (LA) asbestos is associated with increased incidences of human autoimmune disease and mortality related to cardiovascular diseases. However, the systemic and vascular impacts are less well examined because of the dominance of pulmonary disease. It was postulated that regardless of the type of exposure scenario, LA exposure might produce systemic and vascular inflammogenic and thrombotic alterations in healthy and cardiovascular compromised rat models. Samples from three independent studies were examined. In the first study, male Wistar Kyoto (WKY), spontaneously hypertensive (SH), and SH heart failure (SHHF) rats were intratracheally instilled once with 0 (vehicle), 0.25, or 1 mg/rat of LA. In the second study, F344 rats were instilled with vehicle or LA at 0.5, 1.5, or 5 mg/rat. In the third study, F344 rats were instilled with the same mass concentrations of LA delivered by biweekly multiple instillations over 3 mo to simulate an episodic subchronic exposure. Complete blood count, platelet aggregation, serum cytokines, and biomarkers of systemic and aortic effects were examined. LA reduced adenosine diphosphate (ADP)-induced platelet aggregation and decreased circulating platelets in WKY (1 mg/rat) and F344 (5 mg/rat) at the 3-mo time point but did not do so in SH or SHHF rats. A decline in circulating lymphocytes with age appeared to be exacerbated by LA exposure in F344 rats but the differences were not significant. Aorta mRNA expression for biomarkers of oxidative stress (HO-1, LOX-1), inflammation (MIP-2), and thrombosis (tPA, PAI-1, vWf) were increased at baseline in SH and SHHF relative to WKY. LA exposure upregulated several of these biomarkers and also those involved in aortic contractility of WKY rats at 3 mo, suggesting thrombogenic, vasocontractile, and oxidative stress-mediated impairments. The aorta changes in F344 rats were less remarkable than changes noted in WKY following LA exposure. In conclusion, exposure to LA decreased circulating platelets and platelet coagulability while increasing the expression of oxidative stress, thrombosis, and vasoconstriction biomarkers in the aorta of healthy rats. These changes were similar to those noted at baseline in SH and SHHF rats, suggesting that LA-induced pulmonary injury might increase the risk of developing cardiovascular disease in healthy individuals.

Descriptive analysis of the respiratory health status of persons exposed to Libby amphibole asbestos

ObjectiveDescribe respiratory health and quality of life in persons exposed to Libby amphibole asbestos (LAA) contaminated vermiculite.DesignCross-sectional descriptive.SettingAsbestos-related disease clinic in Libby, Montana USA.Participants329 individuals exposed to LAA; mostly men,...

LUNG CANCER MORTALITY RISK AMONG AN OCCUPATIONAL COHORT EXPOSED TO A MIXTURE OF COMMERCIAL AND NON-COMMERCIAL AMPHIBOLE ASBESTOS FROM VERMICULITE MINING OPERATIONS IN LIBBY, MONTANA

Background and Aims: Vermiculite mining and milling in Libby, MT supplied the majority of North American demand for vermiculite during the 20th century. Libby vermiculite is contaminated with amphibole asbestos, including, winchite, richterite and tremolite. Libby workers and residents in the community were exposed to this mixture of largely non-commercial asbestos fibers for decades. Several million homes in North America may have vermiculite attic insulation from the Libby, MT mine. Methods: Our analysis is based on 880 workers hired after 1959 when fiber concentrations were lower and possibly more consistent with potential environmental exposure. We used Cox proportional hazards models with time-dependent covariates to assess the effects of Libby amphibole asbestos on lung cancer mortality. Multiple exposure metrics including cumulative exposure, residency-time weighted exposure, and metrics mathematically allowing for effects of fiber clearance or translocation were evaluated. We compared lung cancer potency results using slopes and their corresponding risks with the slopes and risks from other investigations of the Libby worker cohort. Results: There are four researchers who have recently published lung cancer potency results for the Libby amphibole asbestos worker cohort: Sullivan (2007), Berman and Crump (2008), Larson et al. (2010) and Moolgavkar et al. (2010). The adjusted lung cancer mortality slopes per calendar year from these four studies ranged from 1.6x10E-3 to 4.2 x10E-3 per fiber/cc-year. Risks derived through life tables based on age-specific cancer mortality rates from these four studies ranged from 0.01 to 0.08 per fiber/cc. Uncertainties in the application of these epidemiologic data are discussed. Conclusions: Libby amphibole asbestos, a mixture composed primarily of non-commercial amphibole asbestos, has repeatedly been shown to be associated with lung cancer mortality by different investigators using varying definitions of this occupational cohort. Disclaimer: This abstract does not necessarily reflect EPA policy.