Non-asbestiform elongate mineral particles and mesothelioma risk: Human and experimental evidence.

The presentations in this session of the Monticello II conference were aimed at summarizing what is known about asbestiform and non-asbestiform elongate mineral particles (EMPs) and mesothelioma risks based on evidence from experimental and epidemiology studies. Dr. Case discussed case reports of mesothelioma over the last several decades. Dr. Taioli indicated that the epidemiology evidence concerning non-asbestiform EMPs is weak or lacking, and that progress would be limited unless mesothelioma registries are established. One exception discussed is that of taconite miners, who are exposed to grunerite. Drs. Mandel and Odo noted that studies of taconite miners in Minnesota have revealed an excess rate of mesothelioma, but the role of non-asbestiform EMPs in this excess incidence of mesothelioma is unclear. Dr. Becich discussed the National Mesothelioma Virtual Bank (NMVB), a virtual mesothelioma patient registry that includes mesothelioma patients' lifetime work histories, exposure histories, biospecimens, proteogenomic information, and imaging data that can be used in epidemiology research on mesothelioma. Dr. Bernstein indicated that there is a strong consensus that long, highly durable respirable asbestiform EMPs have the potential to cause mesothelioma, but there is continued debate concerning the biodurability required, and the dimensions (both length and diameter), the shape, and the dose associated with mesothelioma risk. Finally, Dr. Nel discussed how experimental studies of High Aspect Ratio Engineered Nanomaterials have clarified dimensional and durability features that impact disease risk, the impact of inflammation and oxidative stress on the epigenetic regulation of tumor suppressor genes, and the generation of immune suppressive effects in the mesothelioma tumor microenvironment. The session ended with a discussion of future research needs.

Reconstructing Historical Exposures to Respirable Dust and Respirable Silica in the Taconite Mining Industry for 1955-2010.

The goal of this study was to reconstruct the historical respirable silica (RS) and respirable dust (RD) exposures of workers in the Minnesota taconite industry from 1955 to 2010 as part of several epidemiological studies for assessing the association between exposure to components of taconite dusts and the development of respiratory diseases. A job-exposure matrix (JEM) was developed that uses 9127 RS and 19 391 RD occupational hygiene historical measurements. Historical RS and RD data were extracted from several sources and were grouped into seven mines and then into eight departments [Concentrating, Crushing, Janitor, Mining, Office/control room, Pelletizing, Shop (mobile), and Shop (stationary)]. Within each department, we applied a two-level random-intercept regression model which assumes that the natural log of Y (RD or RS concentration) changes over time at a constant rate. Among all predicted RD and RS values, we found that larger RD values were located in the following departments: Crushing, Concentrating, Pelletizing, and Shop (mobile). Larger RS values were located only in either Crushing or Shop (mobile). The annual rates of change for historical RD and RS exposures were between -3.3 and 3.2%. The silica percentage in the dust varied by mine/department with the highest value of 29.3% in Mine F (Crushing) and the lowest value of 2.1% in Mine B (Pelletizing). The predicted historical RD and RS arithmetic mean exposures ranged between <0.075 and 3.14 mg m-3, and between <0.005 and 0.36 mg m-3, respectively. The result of this study is a JEM by mine, department, and year for RD and RS for epidemiological studies.

A Bayesian Approach for Determining the Relationship Between Various Elongate Mineral Particles (EMPs) Definitions.

A variety of dimensions (lengths and widths) of elongate mineral particles (EMPs) have been proposed as being related to health effects. In this paper, we develop a mathematical approach for deriving numerical conversion factors (CFs) between these EMP exposure metrics and applied it to the Minnesota Taconite Health Worker study which contains 196 different job exposure groups (28 similar exposure groups times 7 taconite mines). This approach comprises four steps: for each group (i) obtain EMP dimension information using ISO-TEM 10312/13794 analysis; (ii) use bivariate lognormal distribution to characterize overall EMP size distribution; (iii) use a Bayesian approach to facilitate the formation of the bivariate lognormal distribution; (iv) derive conversion factors between any pair of EMP definitions. The final CFs allow the creation of job exposure matrices (JEMs) for alternative EMP metrics using existing EMP exposures already characterized according to the National Institute of Occupational Safety and Health (NIOSH)-defined EMP exposure metric (length >5 µm with an aspect ratio ≥3.0). The relationships between the NIOSH EMP and other EMP definitions provide the basis of classification of workers into JEMs based on alternate definitions of EMP for epidemiological studies of mesothelioma, lung cancer, and non-malignant respiratory disease.

The impact of different approaches to exposure assessment on understanding non-malignant respiratory disease risk in taconite miners.

INTRODUCTION: We examined the association between cumulative silica exposures in taconite mining and non-malignant respiratory disease (NMRD) using a comprehensive assessment of current and historical exposure measurements in a cross-sectional study of Minnesota taconite mining workers. We also explored the impact of exposure measurement methods by comparing estimated exposure risk from two different exposure measurement modeling approaches. METHODS: Miners were screened with an occupational and medical history questionnaire, spirometry testing and chest x-rays per ILO guidelines. Current and historical occupational exposure assessments were obtained, the former measuring about 679 personal samples over the period of the study for respirable dusts, including silica, in 28 major job functions. Cumulative silica exposure ((mg/m3) × years) was estimated as a cumulative product of time worked and year-specific silica job exposure concentrations. Chest x-ray abnormalities were based on B-reader agreement with a third B-reader for arbitration. Forced vital capacity (FVC) less than lower limits of normal for age, height, race and gender was used to determine spirometric restrictive ventilatory defect (RVD). Prevalence ratios (PR) of exposure-outcome associations, with 95% confidence intervals (CI), were estimated using multivariate Poisson regression. RESULTS: Cumulative silica exposure was associated with RVD prevalence (PR = 1.41, 95% CI = 1.09-1.81) and prevalence of parenchymal abnormalities on chest x-ray (PR = 1.30, 95% CI = 1.00-1.69) using exposure estimates based primarily on current study measurements, and assuming unchanged historical exposure trend. Conversely, when exposures were defined incorporating available actual historical values, no associations were observed between silica exposure and either RVD (PR = 0.76, 95% CI = 0.41-1.40) or parenchymal (PR = 0.87, 95% CI = 0.45-1.70) outcomes. CONCLUSIONS: This study demonstrated that the estimated association between silica dust exposure and lung disease is highly sensitive to the approach used to estimate cumulative exposure. Cumulative values based on conservative estimates of past exposure, modeled from recently measured respirable silica, showed an association with restriction RVD on spirometry. Silica exposure was also significantly associated with increased parenchymal findings on chest x-ray using this approach. Conversely, these findings were absent when actual available historical data was used to estimate cumulative silica exposure. These differences highlight the challenges with estimating occupational dust exposure, the potential impact on calculated exposure risk and the need for long term quality exposure data gathering in industries prone to risk from inhaled respirable dusts.

Reconstructing historical exposures to elongate mineral particles (EMPs) in the taconite mining industry for 1955-2010.

As part of ongoing epidemiological studies for assessing the association between exposure to dust from taconite operations and the development of respiratory diseases, the goal of this study was to reconstruct the exposures of workers to elongate mineral particle (EMP) in the Minnesota taconite mining industry from 1955-2010. Historical NIOSH-7400 and equivalent EMP personal exposure data were extracted from two sources: (1) the Mine Safety and Health Administration (MSHA) online database recorded for all inspection results since 1978 with 655 EMP monitoring records from 1978-2010 for 13 MSHA Mine IDs associated with this study; and (2) the mining companies' internal monitoring reports contained 96 personal EMP exposure records. NIOSH-7400 EMP personal exposures were measured for workers in different jobs in all active mines in 2010 by obtaining 1,285 personal samples. After data treatment, all data were grouped into seven mines and eight departments. Within each mine-department, the yearly EMP mean concentration in f/cc for each year of operation was predicted using two approaches. The performance of two approaches varied by situation. The assumptions underlying each approach described in this article have limitations. A linear regression based on limited historical measurements and those made in 2010-2011 (Approach 1) does not yield reasonable and plausible values of the slope. Approach 2 assumes that the EMP and the respirable dust in the same department share the same historical time trend. This approach allowed us to avail of the more reasonable slope estimates from the historical respirable dust data set and yielded more plausible historical exposure estimates for most locations. This work with two different job exposure matrix (JEMs) provides a unique research opportunity to study the potential impact of exposure assessment to epidemiological results. Both JEMs are being used to assess associations between EMP and respiratory disease in epidemiological studies.

Ambient Fine Aerosol Concentrations in Multiple Metrics in Taconite Mining Operations.

Studies in environmental epidemiology and of occupational cohorts have implicated the effects of fine particulates with increased risk of cardiovascular diseases. Motivated by this evidence, we conducted an ambient air monitoring campaign to characterize fine aerosol concentrations around various taconite ore processes in six taconite mines in northeastern Minnesota. The ore processes were first categorized into 16 broad work areas/buildings. We then took air samples at 91 fixed locations using an array of direct-reading instruments to obtain measurements of mass (PM2.5 or particles with aerodynamic diameter <2.5 µm, and respirable particulate matter or RPM), alveolar-deposited surface area (ADSA), and particle number (PN) concentrations. At each location, a respirable gravimetric pump (which was used for calibration purposes) and the instruments measured the ambient dust level for 4 h producing ~240 1-min averaging real-time measurements. To analyze these data, we fit a Bayesian hierarchical model with an autoregressive order 1 correlation structure to estimate pooled concentrations for the 16 work areas/buildings while accounting for temporal correlation. PM2.5 and RPM average ambient concentrations were highly correlated to each other (Pearson's correlation = 0.98), followed by ADSA and PN correlation (R = 0.77). Office and control room areas were found to have the lowest concentrations in all four metrics when compared to other groups. Distinguishing between concentration levels among the remaining groups was more difficult due to the high uncertainty associated with the geometric mean estimates. The geometric standard deviation within location (GSDWL) generally ranged from 1 to 3 for all exposure metrics, except for a few locations that may have had changes in the work activities that generated the observed peaks and variability during the sampling duration. The geometric standard deviation between locations estimates were generally higher than GSDWL, which may indicate larger variability in the processes/activities between locations within each broad work area/building. Future work may look into whether it is feasible to use area measurements for epidemiological investigation and use personal measurements (if available) to validate such approach.

Mesothelioma and other lung disease in taconite miners; the uncertain role of non-asbestiform EMP.

The purpose of this paper was to assess the role of non-asbestiform amphibole EMPs in the etiology of mesotheliomas and other lung disease in taconite (iron ore) miners. Increased mesothelioma rates have been described in Minnesota taconite workers since the late 1990s. Currently, over 100 cases have been reported by the Minnesota Department of Health within the complete cohort of miners in Minnesota. Geologic sampling has indicated that only the eastern part of the iron range contains non-asbestiform amphibole elongate mineral particles (EMPs), in close proximity to the ore. This type of EMP has been less studied and also exists in talc and gold mining. A series of investigations into the state's taconite industry have been recently completed. Results from a cohort mortality study indicated an SMR of 2.77 (95% CI = 1.87-3.96) for mesothelioma. In a case-control study, the odds ratio for mesothelioma for high vs. low EMP exposure was 2.25 (5% CI = 1.13-4.5) but EMPs in this study were counted by phase contrast microscopy. Odds ratios were not elevated in mines located in the eastern part of the Mesabi iron range. The overall findings suggest that mesothelioma in taconite miners is related to EMP exposure. Because of the way EMPs were counted, results from these studies cannot allow a firm conclusion about the association between EMP exposure and the reported excess mesothelioma.

Pleural abnormalities and exposure to elongate mineral particles in Minnesota iron ore (taconite) workers.

BACKGROUND: Iron ore (taconite) mining and processing are an important industry in northern Minnesota and western Michigan. Concerns around exposures have centered largely on exposure to non-asbestiform amphibole elongate mineral particles (EMPs) found in the eastern portion of the Minnesota iron range. METHODS: A cross sectional survey was undertaken of current and former taconite workers and spouses along with a detailed exposure assessment. Participants provided an occupational history and had a chest radiograph performed. RESULTS: A total of 1188 workers participated. Potential exposures to non-amphibole EMPs were evident across multiple jobs in all active mines. Pleural abnormalities were found in 16.8% of workers. There was an association of pleural abnormalities with cumulative EMP exposure that was not specific to the eastern portion of the range. CONCLUSION: There was evidence of a mild to moderate increase in pleural abnormalities in this population of miners, associated with geographically non-specific cumulative EMP exposure.

A comprehensive assessment of exposures to respirable dust and silica in the taconite mining industry.

This study assessed the present-day levels (year 2010-2011) of exposure to respirable dust (RD) and respirable silica (RS) in taconite mines and evaluated how the mining process influences exposure concentrations. Personal samples (n = 679) were collected to assess exposure levels of workers to RD and RS at six mines in the Mesabi Iron Range of Minnesota. The RD and RS concentrations were measured using the National Institute for Occupational Safety and Health (NIOSH) 0600 and NIOSH 7500, respectively. Between-mine, between-SEG (similar exposure groups), within-SEG, and within-worker components of variability for RD and RS exposures were estimated using a two- or three-way nested random-effects ANOVA model. The majority of RD concentrations across all mines were below the Mine Safety and Health Administration (MSHA) Permissible Exposure Limit (PEL). The highest concentrations of RD were often observed in either the Pelletizing or Crushing departments, which are inherently dusty operations. With a few exceptions, the concentrations of RS in the crushing and concentrating processes were higher than those in the other mining processes, as well as higher than the American Conference of Governmental Industrial Hygienists (ACGIH) Threshold Limit Value (TLV) for RS. The magnetic separation and flotation processes in the concentrating department reduced the levels of RS significantly, and lowered the percentage of quartz in RD in the pelletizing department. There was little variability among the six mines or between the two mineralogically distinct zones for either RD or RS exposures. The between-SEG variability for RS did not differ substantially across most of the mines and was a major component of exposure variance. The within-SEG (or between-worker) variance component was typically the smallest because in many instances one worker from a SEG within a mine was monitored multiple times. Some of these findings were affected by the degree of censoring in each SEG and mine, characteristics of the taconite rock, seasonal effects during sampling, or the tasks assigned to each job in that mine.

A review of mortality associated with elongate mineral particle (EMP) exposure in occupational epidemiology studies of gold, talc, and taconite mining.

BACKGROUND: Mining of gold, taconite, and talc may involve exposure to elongate mineral particles (EMP). The involved EMPs are typically non-asbestiform, include dimensions that regulatory definitions exclude, and have been less studied. METHODS: A review of the literature was undertaken for this exposure and occupational epidemiological studies that occur in gold, talc, and taconite mining. RESULTS: Quantitative EMP exposure information in these industries is incomplete. However, there are consistent findings of pneumoconiosis in each of these types of mining. A recent case-control study suggests a possible association between this exposure and mesothelioma. Lung cancer is inconsistently reported in these industries and is an unlikely outcome of non-asbestiform EMP exposure. There is evidence of cardiovascular mortality excess across all of these types of mining. CONCLUSIONS: Non-malignant respiratory disease and cardiovascular mortality have been consistently increased in these industries. Further investigation, including additional insights for the role of non-asbestiform EMP, is warranted. Am. J. Ind. Med. 59:1047-1060, 2016. © 2016 Wiley Periodicals, Inc.

Increased Lung Cancer Mortality in Taconite Mining: The Potential for Disease from Elongate Mineral Particle Exposure.

Taconite mining involves potential exposure to non-asbestiform amphibole mineral fiber. More recent studies have demonstrated increased mortality from respiratory cancers and heart disease among workers in the taconite industry. This finding is not consistent with recent exposure assessment findings, nor is the toxicology of this mineral suggestive of neoplastic disease. The understanding of respiratory disease in taconite mining is hampered by the lack of exposure data to asbestiform mineral fibers that occurred in the 1950s and 1960s. Other industries with similar mineral exposure have not demonstrated definitive associations with respiratory cancer, although non-malignant respiratory disease is a consistent finding in epidemiological studies.

A case-control study of mesothelioma in Minnesota iron ore (taconite) miners.

OBJECTIVES: An excess of mesothelioma has been observed in iron ore miners in Northeastern Minnesota. Mining and processing of taconite iron ore generate exposures that include elongate mineral particles (EMPs) of amphibole and non-amphibole origin. We conducted a nested case-control study of mesothelioma in a cohort of 68,737 iron ore miners (haematite and taconite ore miners) to evaluate the association between mesothelioma, employment and EMP exposures from taconite mining. METHODS: Mesothelioma cases (N=80) were identified through the Minnesota Cancer Surveillance System (MCSS) and death certificates. Four controls of similar age were selected for each case with 315 controls ultimately eligible for inclusion. Mesothelioma risk was evaluated by estimating rate ratios and 95% CIs with conditional logistic regression in relation to duration of taconite industry employment and cumulative EMP exposure [(EMP/cc)×years], defined by the National Institute for Occupational Safety and Health (NIOSH) 7400 method. Models were adjusted for employment in haematite mining and potential exposure to commercial asbestos products used in the industry. RESULTS: All mesothelioma cases were male and 57 of the cases had work experience in the taconite industry. Mesothelioma was associated with the number of years employed in the taconite industry (RR=1.03, 95% CI 1.00 to 1.06) and cumulative EMP exposure (RR=1.10, 95% CI 0.97 to -1.24). No association was observed with employment in haematite mining. CONCLUSIONS: These results support an association between mesothelioma and employment duration and possibly EMP exposure in taconite mining and processing. The type of EMP was not determined. The potential role of commercial asbestos cannot be entirely ruled out.

Cancer incidence among Minnesota taconite mining industry workers.

PURPOSE: To evaluate cancer incidence among Minnesota taconite mining workers. METHODS: We evaluated cancer incidence between 1988 and 2010 in a cohort of 40,720 Minnesota taconite mining workers used between 1937 and 1983. Standardized incidence ratios (SIRs) with 95% confidence intervals (CIs) were estimated by comparing numbers of incident cancers with frequencies in the Minnesota Cancer Surveillance System. SIRs for lung cancer by histologic subtypes were also estimated. We adjusted for out-of-state migration and conducted a probabilistic bias analysis for smoking-related cancers. RESULTS: A total of 5700 cancers were identified, including 51 mesotheliomas and 973 lung cancers. The SIRs for lung cancer and mesothelioma were 1.3 (95% CI = 1.2-1.4) and 2.4 (95% CI = 1.8-3.2), respectively. Stomach, laryngeal, and bladder cancers were also elevated. However, adjusting for potential confounding by smoking attenuated the estimates for lung (SIR = 1.1, 95% CI = 1.0-1.3), laryngeal (SIR = 1.2, 95% CI = 0.8-1.6), oral (SIR = 0.9, 95% CI = 0.7-1.2), and bladder cancers (SIR = 1.0, 95% CI = 0.8-1.1). CONCLUSIONS: Taconite workers may have an increased risk for certain cancers. Lifestyle and work-related factors may play a role in elevated morbidity. The extent to which mining-related exposures contribute to disease burden is being investigated.

Ambient air pollution and lung disease in China: health effects, study design approaches and future research.

Ambient air pollution in China has worsened following dramatic increases in industrialization, automobile use and energy consumption. Particularly bothersome is the increase in the PM2.5 fraction of pollutants. This fraction has been associated with increasing rates of cardio-respiratory disease in China and elsewhere. Ambient pollutant levels have been described in many of China's cities and are comparable to previous levels in southern California. Lung cancer mortality in China has increased since the 1970s and has been higher in men and in urban areas, the exact explanation for which has not been determined. The estimation of individual risk for Chinese citizens living in areas of air pollution will require further research. Occupational cohort and case-control designs each have unique attributes that could make them helpful to use in this setting. Other important future research considerations include detailed exposure assessment and the possible use of biomarkers as a means to better understand and manage the threat posed by air pollution in China.

Occupational exposures and lung cancer risk among Minnesota taconite mining workers.

OBJECTIVE: To examine the association between employment duration, elongate mineral particle (EMP) exposure, silica exposure and the risk of lung cancer in the taconite mining industry. METHODS: We conducted a nested case-control study of lung cancer within a cohort of Minnesota taconite iron mining workers employed by any of the mining companies in operation in 1983. Lung cancer cases were identified by vital records and cancer registry data through 2010. Two age-matched controls were selected from risk sets of cohort members alive and lung cancer free at the time of case diagnosis. Calendar time-specific exposure estimates were made for every job and were used to estimate workers' cumulative exposures. ORs and 95% CIs were estimated using conditional logistic regression. We evaluated total lung cancer risk and risk of histological subtype by total work duration and by cumulative EMP, and silica exposure by quartile of the exposure distribution. RESULTS: A total of 1706 cases and 3381 controls were included in the analysis. After adjusting for work in haematite mining, asbestos exposure and sex, the OR for total duration of employment was 0.99 (95% CI 0.96 to 1.01). The ORs for quartile 4 versus 1 of EMP and silica exposure were 0.82 (95% CI 0.57 to 1.19) and 0.97 (95% CI 0.70 to 1.35), respectively. The risk of each histological subtype of lung cancer did not change with increasing exposure. CONCLUSIONS: This study suggests that the estimated taconite mining exposures do not increase the risk of developing lung cancer.

Increasing fine particulate air pollution in China and the potential use of exposure and biomarker data in disease prevention.

Increased industrialization and urbanization have led to marked increases in air pollutants in China over the last decade. Pollutant levels in the north and eastern regions are often four times higher than current daily levels in the United States. Recent reports indicate a higher incidence of lung cancer and mortality in men and urban dwellers, but the contribution of air pollution to these findings remains unknown. Future studies that define individual exposures, combined with biomarkers linked to disease, will be essential to the understanding of risk posed by air pollution in China.

Mortality experience among Minnesota taconite mining industry workers.

OBJECTIVE: To evaluate the mortality experience of Minnesota taconite mining industry workers. METHODS: Mortality was evaluated between 1960 and 2010 in a cohort of Minnesota taconite mining workers employed by any of the seven companies in operation in 1983. Standardised mortality ratios (SMR) were estimated by comparing observed deaths in the cohort with expected frequencies in the Minnesota population. Standardised rate ratios (SRR) were estimated using an internal analysis to compare mortality by employment duration. RESULTS: The cohort included 31,067 workers with at least 1 year of documented employment. Among those, there were 9094 deaths, of which 949 were from lung cancer, and 30 from mesothelioma. Mortality from all causes was greater than expected in the Minnesota population (SMR=1.04, 95% CI 1.02 to 1.04). Mortality from lung cancer and mesothelioma was higher than expected with SMRs of 1.16 for lung cancer (95% CI 1.09 to 1.23) and 2.77 for mesothelioma (95% CI 1.87 to 3.96). Other elevated SMRs included those for cardiovascular disease (SMR=1.10, 95% CI 1.06 to 1.14), specifically for hypertensive heart disease (SMR=1.81, 95% CI 1.39 to 2.33) and ischemic heart disease (SMR=1.11, 95% CI 1.07 to 1.16). Results of the SRR analysis did not show variation in risk by duration of employment. CONCLUSIONS: This study provides evidence that taconite workers may be at increased risk for mortality from lung cancer, mesothelioma, and some cardiovascular disease. Occupational exposures during taconite mining operations may be associated with these increased risks, but non-occupational exposures may also be important contributors.