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Journal of Exposure Science and Environmental Epidemiology (2014), 1–8 & 2014 Nature America, Inc. All rights reserved 1559-0631/14

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ORIGINAL ARTICLE

Multiple pathway asbestos exposure assessment for a Superfund community Curtis W. Noonan1, Kathrene Conway1, Erin L. Landguth2, Tracy McNew3, Laura Linker4, Jean Pfau5, Brad Black3, Jaime Szeinuk4 and Raja Flores4 Libby, MT, USA, was the home to workers at a historical vermiculite mining facility and served as the processing and distribution center for this industrial product that was contaminated with amphibole asbestos. Several pathways of environmental asbestos exposure to the general population have been identified. The local clinic and health screening program collects data from participants on past occupational and environmental exposures to vermiculite and asbestos. Health studies among this population have demonstrated associations between amphibole exposure and health outcomes, but critical questions regarding the nature and level of exposure associated with specific outcomes remain unanswered. The objective of this study was to develop a comprehensive exposure assessment approach that integrates information on individuals’ contact frequency with multiple exposure pathways. For 3031 participants, we describe cumulative exposure metrics for environmental exposures, occupational exposures, and residents’ contact with carry-home asbestos from household workers. As expected, cumulative exposures for all three occupational categories were higher among men compared with women, and cumulative exposures for household contact and environmental pathways were higher among women. The comprehensive exposure assessment strategies will advance health studies and risk assessment approaches in this population with a complex history of both occupational and environmental asbestos exposure. Journal of Exposure Science and Environmental Epidemiology advance online publication, 23 April 2014; doi:10.1038/jes.2014.25 Keywords: asbestos; Libby; amphibole; occupational; outdoor activities; residential

INTRODUCTION Libby, MT, USA, is a mountain valley community with a population of B10,000 within a 4-mile radius. This community was the home to workers previously employed at a nearby vermiculite mining facility and also served as the processing and distribution center for this industrial product. The extracted vermiculite was naturally contaminated with what is now termed Libby amphibole asbestos (LA). Excess occupational mortality for asbestos-related conditions was identified in early reports and studies.1–3 Following anecdotal and investigative journalism reports, however, it slowly became evident that the asbestos contamination and human health consequences extended to the general population.4 In 2002, the Libby Asbestos site was added to the National Priorities List of Superfund sites. The intervening years have slowly uncovered a complex story featuring a multitude of exposure pathways, intriguing biomedical responses and an evolving community response. The commercial potential of vermiculite in building insulation and as a soil conditioner was not realized until the early twentieth century. Commercial extraction at this site began in the 1920s and continued until 1990, a period during which the Libby mine produced 80% of the world’s vermiculite. The fibrous contaminant (LA) included asbestiform minerals such as tremolite and actinolite that fall within the regulatory language for amphibole asbestos as well as winchite and richterite, forms that are not described in

current regulatory language.5 The industrial processes associated with the commercial operation included mining, milling, screening, exfoliation, processing and shipping. Each of these processes resulted in high occupational exposures to LA,6 and several studies have demonstrated higher mortality risk among former mine workers for asbestos-related diseases.7,8 The insidious nature of the LA contamination and the integration of industrial processes within the town and transportation corridors resulted in extensive environmental contamination and asbestos exposures among vulnerable general populations. Investigations have described adverse health outcomes and biomarkers among current and former residents exposed to LA through non-occupational pathways.9–12 These studies were limited in their characterization of LA exposure often enumerating or summing the potential LA exposure pathways among study subjects rather than a comprehensive approach that integrates information on contact frequency and the relative importance of a given exposure pathway.13 Federal agencies have conducted several activity-based sampling studies to evaluate a small number of environmental exposure pathways,14–18 but these efforts are of limited utility for reconstructing historical environmental LA exposures via multiple pathways among a diverse population. Early activity-based sampling studies were extremely important in identifying the potential for non-occupational exposure in the contaminated residential community, but the pathways and scenarios evaluated were

1 Center for Environmental Health Sciences, Department of Biomedical Sciences, University of Montana, Missoula, Montana, USA; 2Computational Ecology Laboratory, Division of Biological Sciences, University of Montana, Missoula, Montana, USA; 3Center for Asbestos Related Disease, Libby, Montana, USA; 4Department of Cardiothoracic Surgery, Icahn School of Medicine at Mount Sinai, New York, New York, USA and 5Department of Biological Sciences, Idaho State University, Pocatello, Idaho, USA. Correspondence to: Professor Curtis W. Noonan, Center for Environmental Health Sciences, Department of Biomedical Sciences, 32 Campus Drive, University of Montana, Missoula, MT 59812, USA. Tel.: +1 406 243 4957. Fax: +1 406 243 2807. E-mail: [email protected] Received 20 November 2013; accepted 24 February 2014

Comprehensive asbestos exposure assessment Noonan et al

2 limited.17,18 More recent activity-based sampling efforts have been focused on current potential for exposures with few opportunities to assess exposure concentrations at highly contaminated, pre-cleanup locations.14–16 Thus, new strategies are needed to maximize systematic acquisition and quantification of the extensive exposure history and contact frequency data from patients and study participants in the context of uncertain fiber concentrations for specific historical pathways. In this study we evaluate the exposure histories of patients and screening participants at the Libby-based Center for AsbestosRelated Disease (CARD). For the first time, cumulative measures for several non-occupational LA exposure pathways in this population are described. These approaches can be applied in future studies of asbestos-related disease to more fully inform the community and other stakeholders about the health risks associated with LA. METHODS Patient Population CARD was founded in 2000 to serve as a community health screening and patient care facility to respond to the environmental disaster in Libby and surrounding communities. CARD currently has a patient roster of 45000, but patient records have only been consistently captured in the clinic’s electronic database since 2009. In addition to treating patients, CARD operates the federally funded asbestos disease screening program funded through the 2009 Affordable Care Act. Persons that have not previously been diagnosed with asbestos-related disease and have a history of having lived, worked or recreated for a minimum of 6 months at least 10 years before the screening date are eligible for the screening program. Over 2000 people have participated in the screening program. Data collected by CARD on both patients and screening participants include radiography, spirometry, health history and extensive exposure history assessments. CARD staff also requests that all patients and screening participants consider participation in research activities. If interested, patients and screening participants undergo an informed consent process. The present study includes only those patients and screening participants who have consented to participate in research as of July 2013. Consenting procedures and the use of anonymized clinical data for research purposes has been approved by the Institutional Review Board–Spokane.

Exposure Data Collection Participants complete interviewer-administered questionnaire instruments to describe their experience with occupational and environmental asbestos exposure pathways. The survey instruments are completed at CARD and entered into an electronic database. For the purposes of evaluating participants’ exposure to asbestos and/or Libby vermiculite, there are four general categories of relevant personal history: (1) residence in Libby or Troy (MT, USA); (2) environmental pathways; (3) occupation; and (4) household contact with vermiculite-exposed workers. Each of these categories and the approaches for processing and summarizing the data are described below. Residence in Libby or Troy (MT, USA). Participants provided residential histories, including residency years at specific addresses in Libby and the nearby community of Troy (see Figure 1). These two communities were the most heavily affected by the distribution of vermiculite materials or mining waste for use as fill material or as soil amendment for gardening and landscaping. Over the past several years, and particularly in the years 2001–2004, the US Environmental Protection Agency (EPA) conducted extensive assessment and environmental sampling at 3881 residential properties. A recent study merged these environmental sampling data with a small subset of Libby subjects to yield cumulative exposure estimates in fibers per cubic centimeter for a small number of activities for which there was some activity-based exposure estimates (e.g., disturbance of soil when gardening).19 For a limited number of environmental exposure pathways, this approach may provide useful exposure estimates that would be directly comparable to the general asbestos exposure literature. To evaluate the potential for this database to inform residence-based exposure activities, we first evaluated the frequency of direct matches between the Libby/Troy addresses in the CARD patient database and addresses reported for soil and dust sampling in the EPA database. Based on these findings, we employed a series of geospatial Journal of Exposure Science and Environmental Epidemiology (2014), 1 – 8

analysis approaches to determine the potential for residential sampling results from the EPA database to predict soil and dust concentrations at CARD patient Libby/Troy residences for which there was no direct match to the EPA database. We evaluated residential histories for participants in one of our current studies (n ¼ 169). From these histories, we identified 36 Libby/Troy residences with a direct match to the EPA sampling database. We wrote a script in Python (v2.7.6) to construct 15, 25 and 50 m buffers around these 36 locations and identify other nearby residences from the EPA database utilizing the module KDTree with the library Scipy.20 We then evaluated whether the average soil and dust samples for LA at varying distances from the matched residence were more predictive of actual soil and dust samples for LA than what would be predicted from the entire EPA database. Finally, we used spatial autocorrelation techniques21,22 to determine whether LA soil and dust predictions could be improved with the inclusion of geographical distance. Pathways of environmental exposure. Participants reported their experience or contact with various activities and behaviors that have previously been recognized as potential pathways for exposure to Libby amphibole among the general population in the community (see Table 1). For each of 11 pathways, participants reported whether or not they had participated in these activities. If participants answered yes to a particular environmental pathway, they further reported on hours per day, days per year and total years of contact. Using these data we calculated a cumulative metric titled ‘‘activity years’’ for each of these 11 exposure pathways. Weighting factors of 2, 3 or 4 (low, median and high exposure potential, respectively) were based on a review of activity-based sampling studies conducted by USEPA or other relevant investigations (see Supplementary Table 1). A weighting factor of 1 for very low exposure potential was not assigned to any of the currently recognized pathways. The weighting factor of 1 is held in reserve to accommodate future identified pathways that may have very low exposure potential. The weighting factors were assigned to each environmental pathway, yielding a weighted activity-years value.6,14,15,17,18,23–29 Estimates of a cumulative environmental pathways exposure (CEPE) for these 11 environmental pathways were calculated as follows: CEPEij ¼ Hj =24 Dj =365 Yj wj where for each individual i and pathway j, H is the reported frequency of contact with the exposure pathway in hours per day, D is the reported frequency in days per year, Y is the reported frequency in total years and w is the assigned weighting factor. Occupation. Occupational exposure falls into three general categories. First, participants reported whether or not they worked for the vermiculite mining and processing companies Zonolite and/or W.R. Grace, either directly or as a contracted worker. In addition to reporting on total number of years worked, former Zonolite/W.R. Grace workers indicated which job sites they regularly visited during the course of their work. We ranked the exposure potentials of the 10 reported job sites according to previously evaluated industrial hygiene data.6 These workplace air monitoring data were presented as 8-h time weighted averages of fibers per cubic centimeter (f/cc) using optical phase contrast microscopy (PCM). Count rules for PCM measures required that fibers were 45 mm and wider than 0.25 mm. Based on these f/cc ranges for each job site, we grouped jobs with similar or highly overlapping values and assigned weighting factors of 1 to 4 (lowest to highest; Table 2). Workers reported contact with multiple job sites when relevant, but frequency of contact or total years at a particular job site were not captured. Thus, workers were assigned to the weighting factor corresponding to the highest exposure job site reported. Estimates of cumulative vermiculite (Zonolite/W.R. Grace) occupational exposure (CVOE) were calculated as follows: CVOEij ¼ð255=365Þ ð8=24Þ Yj wj where for each individual i assigned to their reported job site j with the highest exposure potential, Y is the reported frequency in total years adjusted for an assumed 225 days per year and 8 h per day, and w is the assigned weighting factor. The second category of occupational history relevant to the study setting includes all local occupations believed to have had opportunities for exposure to vermiculite or Libby amphibole. The CARD questionnaire included eight occupations, and participants reported the number of years they worked locally (i.e., Libby or Lincoln County, MT, USA) in the respective occupations. Local occupations included work at construction, demolition or excavation sites; the Montana railroad industry; work with commercial boilers or incinerators; agriculture or silviculture; cleaning & 2014 Nature America, Inc.


3

WA

Libby

OR

MT

Troy

Kootenai River

Box B

Box A

ID Libby 0

5

10

20 Kilometers 5

Box A

2 6

1

Libby Sites

3

1. Current Baseball Fields 2. Plummer School

7

3. High School Track

4

4. Middle School Track 5. Former Baseball Fields 6. Vermiculite Bagging Facility 7. Ore Processing Facility Former Export Plant

0

0.5

1

2 Kilometers

8. Conveyor Belt 9. Screening Plant

Rainy Creek Road

Mine Boundary

Box B

8

Lumber Mill Site Popular Fishing Hole Railroad

9

0

0.375

0.75

1.5 Kilometers

Figure 1. Study area showing locations of the residential communities, sites relevant to environmental exposure pathways and the former mine and related operations.

residences or businesses; logging; plywood manufacturing; or other wood processing or finishing. Each of these local occupational sites or activities involved the potential for disturbing dust containing vermiculite or Libby amphibole. For example, amphibole-contaminated vermiculite was broadly distributed throughout the country via rail, and hence local railroad workers and associated occupations had increased risk of exposure. Similarly, any activity involving the disturbance of contaminated soils or indoor dust carried the potential for amphibole exposure given the wide usage of vermiculite materials locally as both soil amendment and residential insulation. These local occupations were all assigned an equal weighting factor given the uncertainty regarding the respective exposure potentials. Estimates of cumulative local, non-mining, occupational vermiculite exposure (CLOE) were calculated as follows: CLOEij ¼ð255=365Þ ð8=24Þ Yj where for each individual i reporting local occupation j, Y is the reported frequency in total years adjusted for an assumed 225 days per year and 8 h per day. The third occupational category includes reporting of occupational contact with materials previously identified in the literature to be associated with an increased risk of exposure to any asbestos. The CARD questionnaire included 12 such materials: brake or clutch linings; hightemperature gaskets; cement sheets, pipes or heat-resistant panels; insulation; electric cloth wrap or high-temperature wiring; fire-proofing materials; heat-protective clothing such as gloves, aprons or coats; joint compounds and sheetrock/drywall; heating and ventilation ducts or duct connecting materials; roofing materials; thermal taping compounds; and & 2014 Nature America, Inc.

heat-resistant plastic parts such as Bakelite. When relevant, participants reported the total years with occupational exposure to each of the listed materials. Weighting factors were not assigned to the materials because an equivalent relative exposure intensity was assigned to all of these materials in a previous asbestos job exposure matrix review.30 Estimates of cumulative materials occupational exposure (CMOE) were calculated as follows: CMOEij ¼ð255=365Þð8=24ÞYj where for each individual i reporting occupational exposure to material j, Y is the reported frequency in total years adjusted for an assumed 225 days per year and 8 h per day. Sharing a household with a Zonolite/W.R. Grace worker. The fourth general category of exposure summarizes participants’ contact with household members who had potential occupational exposure to vermiculite or LA in dust. This category of exposure is, therefore, both environmental and quasi-occupational in nature. Participants reported whether the household contact worked for Zonolite/W.R. Grace, or as a contract worker for Zonolite/W.R. Grace, or as a worker who may have had significant exposure to vermiculite but who did not work at or for Zonolite/ W.R. Grace. Household contacts in the latter occupational category was reported in response to the question ‘‘Did you share a household with anyone who may have had significant exposure to vermiculite who did NOT work at or for WR Grace?’’ With one exception, however, participants were not asked to report on the specific occupation of the household contact. The exception was that participants were asked to Journal of Exposure Science and Environmental Epidemiology (2014), 1 – 8


4 Table 1.

Descriptions and weighting factors for environmental exposure pathways. Weighting factora

Number (%)b of participants reporting exposure pathway

Mean (SD) weighted activity-yearsc

This was a very dusty public access gravel road that was used to haul uncovered vermiculite ore from the mill to the screening plant. A poorly covered conveyor belt that leaked dust transported ore over the river contaminating this area with clouds of dust. The processing plant was adjacent to the ballfields, and the surface substrate of these fields was vermiculite ore. Highest exposures occurred with manicuring and dragging the fields and during the annual Logger Days festival. Local children would regularly play in piles by swinging from ropes, immersing themselves and repeatedly throwing the sparkling material into the air. The piles were located in downtown Libby outside of the processing/ export plant and next door to the ballfields. The Middle School track was covered in vermiculite ore until it was paved in 1981 or 1982 after company studies showed potentially significant fiber exposure to individuals running behind another runner. Bags of raw ore were distributed to students for expanding as part of science lessons. This was a common activity outside of school as well because the raw ore was easily accessible. This road to the mine was regularly used to collect firewood because of its close proximity to town and easy access. Dust from the mine was heavy in this area throughout the years the mine was open Many locals would install their own insulation in attics and walls because the product was readily accessible. Loose insulation was often poured into concrete building blocks. Free, readily available vermiculite was added to many local gardens to retain moisture and loosen soil.

2

1846 (60.9%)

0.17 (0.60)

3

1605 (53.0%)

0.22 (1.04)

2

2548 (84.1%)

0.10 (0.35)

4

1442 (47.6%)

0.22 (0.78)

2

1057 (34.9%)

0.06 (0.21)

3

1510 (49.8%)

0.02 (0.08)

3

972 (32.1%)

0.12 (0.48)

4

1021 (33.7%)

0.21 (1.68)

3

1900 (62.7%)

0.39 (0.97)

Ore piles located at the screening plant were open and assessable to the public at no charge for personal use in gardens and yards as well as for driveway surface material. Wood is and was a primary heat source in the area. Tree bark as well as ash has been shown to contain fibers.

4

972 (32.1%)

0.06 (0.51)

2709 (89.4%)

0.01 (0.01)

Pathway (CARD questionnaire language)

Historical context of pathway

Recreational activities (hunting, hiking, etc) along Rainy Creek Road? Fishing on the Kootenai River near the mouth of Rainy Creek? Playing in or watching games at the downtown ballfields? Playing in or around the vermiculite piles?

Using the Libby Middle School track beyond scheduled gym classes? Heating vermiculite ore to make it expand or pop? Cutting or collecting firewood near Rainy Creek Road? Handling vermiculite insulation outside of any job? Gardening in soil that was observed or known to contain vermiculite? Shoveling and/or hauling vermiculite outside of work? Burning firewood in your home? a

See Supplementary Table 1. Of the total of 3031 participants. c mean (sd) calculated from among those reporting some exposure to a given pathway. b

Table 2.

Weighting factors for occupational exposures at Zonolite/W.R. Grace mine.

CARD terms used in patient questionnaires

Translation to terms used in previous industrial hygiene study (Amandus et al., 1987)6

Range (f/cc)a

Weighting factor

Dry mill Screening plant Expansion plant Mine Laboratory Wet mill Shop Garage/warehouse Town office Other

Dry mill River station, conveyor, tunnel; screen plant Includes verxite plant, bagging plant Includes drilling and mine-non-drilling Quality control laboratory Wet mill Service area by mill Based on ‘‘bus ride’’ and ‘‘transfer point’’ Downtown office building --

16.6–182.1 0.5–112.5 1.2–22.6 0.8–23.0 0.6–13.1 0.8–7.0 0.2–3.8 0.0–2.2 0.0 --

4 4 3 3 3 3 2 2 1 1

a

Fibers per cubic centimeter.

specifically report if their household contact worked at the local lumber mill, a site known to have been contaminated with Libby amphibole at some point in the past. Participants were not asked whether they had a household contact with past employment in other asbestos-related occupations or exposure to the asbestos materials represented in the CMOE metric above. Journal of Exposure Science and Environmental Epidemiology (2014), 1 – 8

In this context of household contacts, participants further reported on particular exposure pathways. First, they were asked whether the household worker wore ‘‘visibly dusty work clothes home.’’ Second, they were asked whether the household worker wore ‘‘visibly dust-contaminated clothing in the household car.’’ For each of these pathways, participants reported the applicable number of days per year and total & 2014 Nature America, Inc.


5 years. The cumulative exposure metric for exposure to dusty clothes was further adjusted by the exposure factor of 73.6 min per day (1.23 h per day) for assumed time that an adult spends in the laundry/utility room.31 The cumulative exposure metric for exposure to dust in the car was further adjusted by the exposure factor of 93.8 min per day (1.56 h per day) for assumed time that an adult spends in the car.31 These cumulative exposure metrics were further weighted (1 to 4) according to the occupation category of the household contact. If the household contact was a former worker at, or contractor for, Zonolite/W.R. Grace, a weighting factor of 4 was assigned. If the household contact worked at the mill, a weighting factor of 3 was assigned. Other occupations with potential for vermiculite exposure were assigned a weighing factor of 2. When a household contact exposure was indicated but the occupation was not specified, a weighting factor of 1 was assigned. Participants also reported on whether or not they spent time at another person’s home where a vermiculite worker lived. This exposure pathway was summarized by the participant’s corresponding report of average hours per day, average days per year and total years that they spent at this other home. The occupational category associated with these other home contacts was not reported, and hence the cumulative exposure metric for visiting another person’s home where a vermiculite worker lived was given a weight of 1. Estimates of cumulative exposure to dust from household contact vermiculite worker (CDHC) were calculated as follows: CDHCi ¼½ð1:23=24Þ ðHDi =365Þ HYi wi þ ½ð1:56=24Þ ðCDi =365Þ CYi wi þ ½ðVHi =24Þ ðVDi =365Þ VYi where for each individual i reporting at least one of the three household contact pathways, HD and HY are the reported days per year and total years that a household vermiculite worker wore visibly dusty work clothes home adjusted for an assumed 1.23 h per day contact and the assigned weighting factor (w) according to occupation of the household contact; CD and CY are the reported days per year and total years that a household vermiculite worker wore visibly dust-contaminated clothing in the household car adjusted for an assumed 1.56 h per day contact and the assigned weighting factor (w) according to occupation of the household contact; and VH, VD and VY are the reported hours per day, days per year and total years that the individual visited another person’s home where a vermiculite worker lived.

Data Analysis All exposure data sets are merged and analyzed using SAS v9.3 (Cary, NC, USA). Summary statistics for cumulative exposure metrics were generated and evaluated with respect to participant’s age and sex. Comparisons between groups were evaluated by analysis of variance or w2 test. The several cumulative metrics describe different exposure pathways, but it was possible that many of these metrics would co-vary among participants. To the degree that these metrics were strongly correlated among participants, the future potential for identifying associations between a single cumulative exposure metric and health outcomes may be limited. To assess the correlation between cumulative exposure metrics, we evaluated Spearman’s rank order correlations.

RESULTS The CARD database included 3729 patients or screening participants aged Z18 years. Of these, 3123 (83.7%) provided consent for research and comprise the pool of available records for this descriptive exposure assessment study. The mean age (SD) among those who had provided research consent was 58.0 (12.7) years as compared with 59.2 (14.9) years among those who had not provided research consent (t ¼ 1.97, P ¼ 0.05). The gender distribution was slightly different between the two groups, with 46.5% women among those who had provided research consent compared with 41.6% women among those who had not provided research consent (w2 ¼ 4.91, P ¼ 0.027). Residential histories from the CARD patient database indicated 11,617 Libby/Troy addresses, allowing for multiple counts of a single address if more than one patient reported a history at that address. From this total, only 3391 (29.2%) of the total had a direct & 2014 Nature America, Inc.

match to the residences in the EPA sampling database. We explored methods to use the extensive EPA sampling database to impute soil and dust exposure concentrations at the more than 8000 CARD patient residences that did not match an EPA sampling location. Geospatial analysis approaches did not result in reliable prediction of soil and dust LA concentrations when including EPA results from sampling locations within any of the evaluated buffer zones (i.e., 15, 25 and 50 m, data not shown). Spatial autocorrelation techniques to include geographic distance did not improve the potential for using the EPA soil and dust sampling database to inform exposure concentrations at unmatched residences. Specifically, nearly random spatial configuration was suggested by Moran’s I global values of 0.016 and 0.006, respectively. Thus, the use of the extensive residential exposure sampling data for assigning quantitative exposure estimates to participants remains untenable for large patient population studies. Here, we summarize residential history according to years resided in the communities of Libby or Troy. We characterized the residential history of participants before 1990, the year the mine closed. Among the 3123 participants, 2232 (71.5%) lived in Libby, 142 (4.5%) lived in Troy and 208 (6.6%) lived in both Libby and Troy for some periods before 1990. Among all 3123 participants, the mean (SD) years of residence in one or both of these communities before 1990 was 15.3 (12.6) years. Of the 2440 participants with some residence time in Libby, the mean (SD) years of residence in Libby before 1990 was 17.8 (11.4) years. Of the 350 participants with some residence time in Troy, the mean (SD) years of residence in Troy before 1990 was 12.6 (9.9) years. For comparison across cumulative exposure metrics, we limited the correlation analysis and summary statistics to participants who had non-missing data for all exposures (n ¼ 3031). The environmental exposure pathways and corresponding weighting factors are described in Table 1. For further description of the derivation of these weighting factors and the data upon which they are based, see Supplementary Table 1. Contact with these environmental exposure pathways among participants was common, ranging from 32% to 89% of all respondents. Table 2 shows the weighting factors assigned to particular job tasks among former employees or contract workers of the Zonolite/W.R. Grace mine and the corresponding historical air sampling summaries. The Spearman’s correlations between the cumulative exposure metrics are presented in Table 3. Significant correlations were observed for 22 of the 28 comparisons, but the correlation coefficients for 18 of the 22 significant correlations were small or modest (ro0.20). Of the four large correlations, three occurred within the household contact grouping (i.e., exposure at home or in the car to dusty clothes from a mine worker or visits to a mine worker household, r ¼ 0.38 to 0.88). As the three metrics describe similar exposure pathways (i.e., household contact with worker take-home LA), we combined these three metrics into one cumulative household contact metric for summary purposes (CDHC, as described above). The cumulative metric for working in Lincoln County occupations with potential exposure to vermiculite materials was modestly correlated with occupational history of contact with asbestos materials (r ¼ 0.29). As the two occupational metrics describe potential exposure to different materials (i.e., LA versus mixed fiber exposures), the cumulative metrics were kept separate for summary purposes. Table 4 describes summary measures of the cumulative exposure metrics by sex and age group. Residential years in Libby or Troy and the cumulative occupational exposure metrics increased with age groups among both women and men. Cumulative exposures for all three occupational categories were higher among men compared with women. For example, the mean (SD) years working as a W.R. Grace employee or contractor was 0.75 (3.25) for men and 0.02 (0.31) for women. In contrast, combined cumulative exposures for take-home pathways (CDHC) Journal of Exposure Science and Environmental Epidemiology (2014), 1 – 8


6 Table 3.

Spearman’s rank correlations (r; P-value) between cumulative exposure metrics for participants (n ¼ 3031).

Years resident in Libby or Troy, MT, USA, before 1990 CEPE

Residential history

Environmental Pathways

Occupational history

Years resident in Libby or Troy, MT before 1990

Cumulative environmental pathways exposure (CEPE)

Cumulative vermiculite occupational exposure (CVOE)a

Cumulative local, nonmining, occupational vermiculite exposure (CLOE)

Cumulative materials occupational exposure (CMOE)

Dusty clothes (home)

Dusty clothes (car)

Visit other home

1.0

0.195 o0.0001

0.071 o0.0001

0.151 o0.0001

0.039 0.032

0.197 o0.0001

0.158 o0.0001

0.17465 o0.0001

1.0

0.130 o0.0001 1.0

0.142 o0.0001 0.177 o0.0001 1.0

0.005 0.763 0.080 o0.0001 0.292 o0.0001 1.0

0.121 o0.0001 0.060 0.001 0.020 0.264 0.017 0.346 1.0

0.072 o0.0001 0.047 0.01 0.037 0.041 0.020 0.2701 0.876 o0.0001 1.0

0.06924 0.0001 0.00590 0.746 0.04988 0.006 0.02257 0.214 0.39831 o0.0001 0.37575 o0.0001

CVOE CLOE CMOE Dusty clothes (home) Dusty clothes (car)

Contact with dust from household vermiculite worker

a

Direct or secondary contract work for Zonolite/W.R. Grace.

were higher among women (mean (SD) ¼ 2.45 (3.34) for women) as compared with men (1.31 (2.13)). Strong sex by age interactions were observed for occupational exposure pathways and take-home pathways (Po0.001). The cumulative mean (SD) metric for environmental exposures was not significantly different by age group (P ¼ 0.235) or by sex (mean (SD) ¼ (0.87 (2.81) for women and (0.77 (1.96) for men, P ¼ 0.254). DISCUSSION The exposure assessment approach presented here is the first time that the various occupational and environmental Libby amphibole exposure pathways for this community have been integrated in a consistent manner. The importance of accurately representing both environmental and occupational Libby amphibole exposure in this population is twofold. First, these exposure assessment measures will be applied to numerous health outcomes investigations that are forthcoming. For example, our group is currently evaluating the influence of autoimmune responses on asbestos-related disease progression. We have previously demonstrated that the Libby population has a higher prevalence of autoantibodies, specifically antinuclear autoantibody (ANA).32 Thus, to appropriately evaluate any causal association between autoimmune response and asbestos-related disease, we will need to account for Libby amphibole exposure among study participants. To date, comprehensive asbestos exposure assessment efforts in this population have been limited, particularly with respect to non-occupational pathways. Second, a comprehensive understanding of LA exposure among this population is necessary for moving forward on risk assessment efforts for this Superfund site that remains an EPA-declared public health emergency. The currently proposed Reference Concentration (RfC) for LA is based upon an occupational cohort from an Ohio industrial site that processed the commercial, asbestos-contaminated vermiculite material, originating in Libby. The occupational cohort is well characterized with respect to quantified exposure estimates supported by historical air monitoring data and with respect to pulmonary outcomes supported by B-read chest radiographs.33,34 However, risk profiles may vary among the environmentally exposed general population at the Libby Superfund site. The exposure assessment strategy presented here does not include fiber concentrations, but the comprehensive cumulative exposure metric approach will enable an Journal of Exposure Science and Environmental Epidemiology (2014), 1 – 8

evaluation of dose-response functions for various health end points among the exposed general population. Establishing doseresponse functions in the target population is one of the foundations of the risk assessment approach and may lend support to the toxicological review currently being considered for LA. As we investigate health outcomes in this population, we will have opportunities to evaluate the relative importance of specific exposure pathways. Findings may indicate that some pathways require additional exposure characterization to determine whether adverse health effects are likely to be associated with levels of LA exposure that may be lower than currently proposed standards. This strategy may be limited by the absence of robust quantified exposure estimates for most of the historical environmental exposure pathways, but our proposed comprehensive exposure assessment strategy would provide the data to support additional activity-based sampling strategies if such efforts would further improve or support risk assessment. The exposure assessment strategy described here could be further improved by utilizing information about changes in exposure probabilities over time. For example, exposure estimates at specific W.R. Grace jobs changed over calendar time,6 and the cumulative occupation metric could be adjusted accordingly. At present, many of the ongoing studies in Libby are focused on evaluating health outcomes among non-occupationally exposed populations in order to inform decisions regarding general population risk. It is noteworthy that we were able to characterize exposure potential among women. With rare exception, health studies of asbestos exposure are limited to men in the occupational setting. Where women have been included in such studies, their exposure potential or follow-up time is often lower than what is described for men.35 These exposure data for the Libby population, particularly the environmental pathway exposure data, point to the strong potential to investigate asbestos-related disease among women. For example, the three summary occupational metric means were 4.4 to 37.5 times higher for men compared with women, but women had comparable cumulative means for the combined environmental exposure pathways (Table 4). As with prior studies of asbestos-exposed women, the take-home exposures are important for this group, showing that cumulative means for take-home exposures among women was almost two times higher than among men. There are several limitations of this comprehensive exposure assessment approach that must be considered. The descriptive & 2014 Nature America, Inc.


7 Table 4.

Mean (SD) of cumulative exposure metrics in years among participants according to sex and age group (n ¼ 3031). Sample size

Residential history Years resident in Libby or Troy, MT, USA, before 1990

Weighted activity-years of cumulative occupational and environmental exposure Cumulative environmental pathways exposure (CEPE)

Cumulative vermiculite occupational exposure (CVOE)a

Cumulative local, non-mining, occupational vermiculite exposure (CLOE)

Cumulative materials occupational exposure (CMOE)

Cumulative exposure to dust from household contact with vermiculite worker (CDHC)

Women All 18–44 years 45–54 years 55–64 years 65–74 years 75 þ years

1412 239 336 463 267 107

15.8 10.1 14.5 16.4 17.4 25.5

(12.3) (7.6) (10.7) (12.3) (13.5) (15.3)

0.87 0.70 0.93 0.84 0.99 0.91

(2.81) (2.95) (3.35) (2.67) (2.28) (2.37)

0.02 0.01 0.02 0.01 0.03 0.10

(0.31) (0.14) (0.28) (0.22) (0.33) (0.72)

0.88 0.67 0.97 0.89 0.97 0.86

(2.42) (2.20) (2.44) (2.37) (2.70) (2.44)

0.31 0.15 0.50 0.34 0.14 0.31

(1.72) (0.89) (2.32) (1.85) (0.91) (1.80)

2.45 1.92 2.68 2.64 2.23 2.69

(3.34) (2.72) (3.58) (3.44) (3.22) (3.53)

Men All 18–44 years 45–54 years 55–64 years 65–74 years 75 þ years

1619 213 356 567 342 141

14.9 8.95 15.2 15.1 15.7 20.8

(12.7) (7.02) (10.7) (12.4) (13.8) (17.6)

0.77 0.47 0.91 0.85 0.72 0.70

(1.96) (1.24) (2.16) (2.32) (1.39) (1.87)

0.75 0.03 0.22 1.04 1.01 1.38

(3.25) (0.33) (1.25) (3.73) (3.80) (4.91)

3.91 1.57 3.52 3.74 4.96 6.48

(5.60) (2.42) (4.69) (4.86) (6.73) (8.56)

3.07 1.51 2.76 3.34 3.94 3.02

(7.55) (3.48) (6.52) (7.98) (9.68) (6.32)

1.31 1.36 1.97 1.36 0.81 0.59

(2.13) (1.90) (2.51) (2.15) (1.84) (1.43)

Comparisons across strata (P-value) Sex 3031 0.068 Age group 3031 o0.001 Sex age 3031 0.052 group

0.254 0.235 0.762

o0.0001 o0.0001 o0.0001

o0.0001 o0.0001 o0.0001

o0.0001 0.0007 0.007

o0.0001 o0.0001 0.0008

a

Direct or secondary contract work for Zonolite/W.R. Grace.

data presented here for the cumulative exposure metrics with respect to age and gender may have limited value for comparison with the occupational asbestos exposure literature. Asbestosexposed occupational cohorts are typically described in terms of f/ cc-years accounting for different settings, job types, materials and changes over time in the use of engineering controls or personal protective equipment. Although such estimates can be calculated for past Zonolite/W.R. Grace workers,6 no reliable fiber quantification data are available for comprehensively estimating LA exposure through environmental pathways or other local occupations with potential for exposure to vermiculite. However, the comprehensive exposure assessment approach described here allows for inclusion of these various grouped pathways in multivariate analyses of health outcomes. The low correlations between exposure groupings suggest a strong potential to detect health associations for particular exposure groupings in multivariate analyses if such true associations are present. Further limitations of this approach, and any attempt to comprehensively assess Libby amphibole exposure, include the assumptions required to establish these cumulative metrics. In this population, there are limited data available for estimating exposure concentrations, yet we still employed a weighting approach for the various exposure pathways. This issue is particularly profound for the presumed environmental exposure pathways. Nevertheless, there are some air sampling data that point to the potential magnitude of exposure for particular contact with LA or vermiculite even if the contact scenario for a particular environmental pathway differs from the scenario represented by the air sampling data. These limited data together with historical knowledge of past exposure scenarios provided reasonable justification for the weighting of the various pathways. In addition to the weighting factors, we made some assumptions with respect to actual time of contact with a given occupation, material or activity. Where possible, we used conservative assumptions such as work days per year and hours per day, or assumptions that & 2014 Nature America, Inc.

were based on data-supported exposure factors.31 The assumptions and weighting factors were consistent within exposure grouping (i.e., environmental, occupational or household contact), but not across exposure groupings. Thus, the cumulative metrics described here should not be summed across exposure grouping, nor should the summary values be compared across exposure groupings. For example, among women the mean cumulative metric for exposure because of take-home dust from household workers is 2.8 times higher than the cumulative metric for environmental exposure pathways, but the relative importance of these exposure groupings will be determined by evaluating how these metrics vary within grouping with respect to asbestos-related health outcomes among women. Finally, all exposure assessment profiles are dependent upon self-reporting by study participants. As with any self-reported data we anticipate that there will be some degree of error. The present exposure assessment analysis was naive to disease status among participants. Future health outcomes studies will be more informative in determining whether exposure reporting error is differential with respect to disease status. In conclusion, we report here a comprehensive multi-pathway exposure assessment approach for amphibole asbestos from contaminated vermiculite. The circumstances surrounding this Superfund site have been previously described as a ‘‘slow moving technological disaster’’.36 The insidious nature of asbestos-related health effects suggests that outcomes assessment in the affected populations and associated risk assessment decisions will continue for decades. The data presented here support a robust exposure assessment approach that integrates the numerous occupational and environmental pathways for use in future LA health risk research. CONFLICT OF INTEREST The authors declare no conflict of interest.

Journal of Exposure Science and Environmental Epidemiology (2014), 1 – 8


8 ACKNOWLEDGEMENTS This research was supported by ATSDR/CDC Grant No. TS000099-01. We thank Ted Larson, ATSDR, for his helpful comments on an early review of this manuscript. We also thank Dave Berry, EPA, for providing historical context and insight on the EPA sampling database.

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