Brett T. McLaurin

The Presence of Asbestos in the Natural Environment is Likely Related to Mesothelioma in Young Individuals and Women from Southern Nevada

Background: Inhalation of asbestos and other mineral fibers is known causes of malignant mesothelioma (MM) and lung cancers. In a setting of occupational exposure to asbestos, MM occurs four to eight times more frequently in men than in women, at the median age of 74 years, whereas an environmental exposure to asbestos causes the same number of MMs in men and women, at younger ages. Methods: We studied the geology of Nevada to identify mineral fibers in the environment. We compared MM mortality in different Nevada counties, per sex and age group, for the 1999 to 2010 period. Results: We identified the presence of carcinogenic minerals in Nevada, including actinolite asbestos, erionite, winchite, magnesioriebeckite, and richterite. We discovered that, compared with the United States and other Nevada counties, Clark and Nye counties, in southern Nevada, had a significantly higher proportion of MM that occurred in young individuals (<55 years) and in women. Conclusions: The elevated percentage of women and individuals younger than 55 years old, combined with a sex ratio of 1:1 in this age group and the presence of naturally occurring asbestos, suggests that environmental exposure to mineral fibers in southern Nevada may be contributing to some of these mesotheliomas. Further research to assess environmental exposures should allow the development of strategies to minimize exposure, as the development of rural areas continues in Nevada, and to prevent MM and other asbestos-related diseases.

Combining surface mapping and process data to assess, predict, and manage dust emissions from natural and disturbed land surfaces

The impact of dust emission on air quality is a significant health and environmental concern. Accurately determining the source (natural versus anthropogenic) and load of dust is an important component of any mitigation effort. We develop an approach to assess dust emission potential based on study of Nellis Dunes Recreation Area, a popular off-road vehicle area close to Las Vegas, Nevada. A mapping approach to assess dust emission potential is presented, which may serve as a template to assess other areas for this hazard. A 1:10,000 map delineating units based upon surficial characteristics affecting dust emission (e.g., soil texture, rock cover, surface crusts, and vegetation) was created. Seventeen surface units are grouped into four major classes (sand, silt and clay, rock covered, and active drainages). A >500 km network of trackways was digitized into a geographic information system (GIS) to determine the distribution of tracks across surface types to assess the density of disturbance. Wind-erosion measurements and off-road experiments using different vehicles (four-wheeler, motorcycle, and dune buggy) were performed on the various surface types to assess the amount of dust generated. Dust emission risk maps for Nellis Dunes Recreation Area are presented for two types of processes: off-road vehicular (ORV) activity and wind erosion. Highest dust emissions for ORV activity occur on map units composed of silt and clay, and on desert pavements. These areas can also produce large amounts of dust through natural wind erosion when disturbed. In contrast, the sandy units produce high emissions through natural wind erosion, and therefore limiting ORV use in those areas provides no benefit to air quality.

Immunotoxicological and neurotoxicological profile of health effects following subacute exposure to geogenic dust from sand dunes at the Nellis Dunes Recreation Area, Las Vegas, NV

Exposure to geogenic particulate matter (PM) comprised of mineral particles has been linked to human health effects. However, very little data exist on health effects associated with geogenic dust exposure in natural settings. Therefore, we characterized particulate matter size, metal chemistry, and health effects of dust collected from the Nellis Dunes Recreation Area (NDRA), a popular off-road vehicle area located near Las Vegas, NV. Adult female B6C3F1 mice were exposed to several concentrations of mineral dust collected from active and vegetated sand dunes in NDRA. Dust samples (median diameter: 4.4 μm) were suspended in phosphate-buffered saline and delivered at concentrations ranging from 0.01 to 100 mg dust/kg body weight by oropharyngeal aspiration. ICP-MS analyses of total dissolution of the dust resulted in aluminum (55,090 μg/g), vanadium (70 μg/g), chromium (33 μg/g), manganese (511 μg/g), iron (21,600 μg/g), cobalt (9.4 μg/g), copper (69 μg/g), zinc (79 μg/g), arsenic (62 μg/g), strontium (620 μg/g), cesium (13 μg/g), lead 25 μg/g) and uranium (4.7 μg/g). Arsenic was present only as As(V). Mice received four exposures, once/week over 28-days to mimic a month of weekend exposures. Descriptive and functional assays to assess immunotoxicity and neurotoxicity were performed 24 h after the final exposure. The primary observation was that 0.1 to 100 mg/kg of this sand dune derived dust dose-responsively reduced antigen-specific IgM antibody responses, suggesting that dust from this area of NDRA may present a potential health risk.

Health effects from exposure to atmospheric mineral dust near Las Vegas, NV, USA

Highlights • Atmospheric geogenic dust comprised of a mineral-metal mixture is a source of exposure in Clark County, Nevada.• Lung exposures over a period of one month to NDRA atmospheric geogenic dust suppressed immune function in a mouse model.• Similar geological desert surfaces emit dust in southern Nevada and elsewhere in the world.• This study is representative of a desert environment; dust composition may vary by source.

Health effects following subacute exposure to geogenic dusts from arsenic-rich sediment at the Nellis Dunes Recreation Area, Las Vegas, NV

Geogenic dust from arid environments is a possible inhalation hazard for humans, especially when using off-road vehicles that generate significant dust. This study focused on immunotoxicological and neurotoxicological effects following subacute exposure to geogenic dust generated from sediments in the Nellis Dunes Recreation Area near Las Vegas, Nevada that are particularly high in arsenic; the naturally-occurring arsenic concentrations in these surficial sediments ranged from 4.8 to 346μg/g. Dust samples from sediments used in this study had a median diameter of 4.5μm and also were a complex mixture of naturally-occurring metals, including aluminum, vanadium, chromium, manganese, iron, cobalt, copper, zinc, strontium, cesium, lead, uranium, and arsenic. Adult female B6C3F1 mice exposed via oropharyngeal aspiration to 0.01 to 100mg dust/kg body weight, four times, a week apart, for 28days, were evaluated 24h after the last exposure. Peripheral eosinophils were increased at all concentrations, serum creatinine was dose responsively increased beginning at 1.0mg/kg/day, and blood urea nitrogen was decreased at 10 and 100mg/kg/day. Antigen-specific IgM responses and natural killer cell activity were dose-responsively suppressed at 0.1mg/kg/day and above. Splenic CD4+CD25+ T cells were decreased at 0.01, 0.1, 10, and 100mg/kg/day. Antibodies against MBP, NF-68, and GFAP were selectively reduced. A no observed adverse effect level of 0.01mg/kg/day and a lowest observed adverse effect level of 0.1mg/kg/day were determined from IgM responses and natural killer cell activity, indicating that exposure to this dust, under conditions similar to our design, could affect these responses.

Surface and Airborne Arsenic Concentrations in a Recreational Site near Las Vegas, Nevada, USA

Elevated concentrations of arsenic, up to 7058 μg g-1 in topsoil and bedrock, and more than 0.03 μg m-3 in air on a 2-week basis, were measured in the Nellis Dunes Recreation Area (NDRA), a very popular off-road area near Las Vegas, Nevada, USA. The elevated arsenic concentrations in the topsoil and bedrock are correlated to outcrops of yellow sandstone belonging to the Muddy Creek Formation (≈ 10 to 4 Ma) and to faults crossing the area. Mineralized fluids moved to the surface through the faults and deposited the arsenic. A technique was developed to calculate airborne arsenic concentrations from the arsenic content in the topsoil. The technique was tested by comparing calculated with measured concentrations at 34 locations in the NDRA, for 3 periods of 2 weeks each. We then applied it to calculate airborne arsenic concentrations for more than 500 locations all over the NDRA. The highest airborne arsenic concentrations occur over sand dunes and other zones with a surficial layer of aeolian sand. Ironically these areas show the lowest levels of arsenic in the topsoil. However, they are highly susceptible to wind erosion and emit very large amounts of sand and dust during episodes of strong winds, thereby also emitting much arsenic. Elsewhere in the NDRA, in areas not or only very slightly affected by wind erosion, airborne arsenic levels equal the background level for airborne arsenic in the USA, approximately 0.0004 μg m-3. The results of this study are important because the NDRA is visited by more than 300,000 people annually.

Oxidative stress and lung pathology following geogenic dust exposure

This study was designed to evaluate markers of systemic oxidative stress and lung histopathology following subacute exposure to geogenic dust with varying heavy metal content collected from a natural setting prone to wind erosion and used heavily for off‐road vehicle recreation. Adult female B6C3F1 mice were exposed to several concentrations of dust collected from seven different types of surfaces at the Nellis Dunes Recreation Area in Clark County, Nevada, designated here as CBN 1‐7. Dust representing each of the seven surface types, with an average median diameter of 4.2 μm, was selected and administered via oropharyngeal aspiration to mice at concentrations from 0.01 to 100 mg of dust kg–1 of body weight. Exposures were given four times spaced a week apart over a 28 day period to mimic a month of weekend exposures. Lung pathology was evaluated while plasma markers of oxidative stress included levels of reactive oxygen and nitrogen species, superoxide dismutase, total antioxidant capacity and total glutathione. Overall, results of these assays to evaluate markers of oxidative stress indicate that no single CBN surface type was able to consistently induce markers of systemic oxidative stress at a particular dose or in a dose–response manner. All surface types were able to induce some level of lung inflammation, typically at the highest exposure levels. These data suggest that dust from the Nellis Dunes Recreation Area may present a potential health risk, but additional studies are necessary to characterize the full extent of health risks to humans. Copyright

The emerging field of medical geology in brief: some examples

Emerging medical problems present medical practitioners with many difficult challenges. Emergent disciplines may offer the medical community new opportunities to address a range of these diseases. One such emerging discipline is medical geology, a science that is dealing with the influence of natural environmental factors on the geographical distribution of health in humans and animals. It involves the study of the processes and causes of diseases and also the use research findings to present solutions to health problems.

Health effects following subacute exposure to geogenic dust collected from active drainage surfaces (Nellis Dunes Recreation Area, Las Vegas, NV)

Graphical abstract

Reply to “No Increased Risk for Mesothelioma in Relation to Natural-Occurring Asbestos in Southern Nevada”

We appreciate the interest and review of our paper1 by Pinheiro and Jin2, as they provide us an opportunity to re-open a dialogue with the Department of Health and Human Services, Nevada, with whom Dr. Pinheiro is associated. Environmental epidemiology is a relatively recent science and, because it deals with small numbers and exposures that cannot be assessed on individuals, it uses specific methods that are different from classical cancer epidemiology3. Pinheiro and Jin: “the proper indicator of risk in a population or a subpopulation is the incidence rate”. While this is often true, it would be incorrect for this situation because most mesotheliomas are due to occupational exposure to asbestos4, therefore, the incidence (or mortality) rates reflect the process and/or use of asbestos in the studied area. Incidence rates cannot distinguish between occupational and environmentally-caused mesotheliomas. Occupational exposure leads to a mesothelioma Male:Female (M:F) sex-ratio of 4–8:1, with a mean age of diagnosis of 74 years-old, because of the 30–50 years latency between initial exposure and mesothelioma development. In places where people were only environmentally exposed to carcinogenic fibers, the M:F sex-ratio is about 1:1 and the mean age of diagnosis is 50–605–7. In places where both types of exposure exist, the M:F sex ratio decreases and the proportion of young (<55 years old) cases increases, compared to places with occupational exposure only. Consequently, we used the significant decrease of mesothelioma M:F sex-ratio and the increase of young cases as indicators of possible environmental exposure to carcinogenic fibers. Pinheiro and Jin: “there is no scientific consensus on the use of the sex ratio and the proportion under 55 as indicators of environmental (non-occupational) exposure to asbestos or NOA”. The epidemiology of mesothelioma from mixed environmental and occupational exposures to carcinogenic fibers has never specifically been studied. However, the studies of populations exposed to carcinogenic fibers from their natural environment, without occupational exposure to asbestos, showed a mesothelioma M:F sex-ratio of about 1:1 and a higher proportion of young cases5–7. There are no published studies contradicting or questioning the methodology we used. The first International Conference On Mesothelioma In Populations Exposed To Naturally Occurring Asbestiform Fibers sponsored by the NCI, NIEHS and IASLC, will be held in Honolulu Nov 9–10; methodology will be one of the topics discussed. We would welcome Drs. Pinheiro and Jin. Pinheiro and Jin: “a male to female sex ratio can be elevated just by virtue of a low number of male cases rather than an actual increased absolute number among females”. Although this statement appears incorrect –M:F would be elevated by an increase in males and /or a decrease in females- , we think we understand what they mean. However, a lower mesothelioma incidence/mortality in male and in old age groups simply reflects a lower occupational exposure to asbestos. In the absence of environmental exposure, a low level of occupational exposure leads to a lower mesothelioma incidence in both males and females, and in both old and young age groups, with a M:F sex-ratio still around 4–8:1, and less than 10% of mesothelioma cases in young individuals. If there is environmental exposure in a region where a low level of occupational exposure exists, the environmental exposure causes additional mesothelioma cases in both males and females, leading to a decreased sex ratio and increased proportion of young mesothelioma cases –as observed in Southern Nevada, while the total incidence in male and in old age groups may still be low compared to regions with higher occupational exposure. Pinheiro and Jin question why the study periods are different in the incidence data that we used to compare mesothelioma incidence by state, and the mortality data that we analyzed by gender, age group and county. The answer is simple: the incidence data that we used are public, available by state only, and 2006–2010 was the longest available period of time, while the Center for Disease Control (CDC) mesothelioma mortality data that we obtained to carry out our analysis by county were available for 1999–2010. Additionally, we merely cited the US states which presented the lowest and highest mesothelioma incidence in the US, the lowest and highest sex ratio, and the lowest and highest proportion of young adults. We did not make any statistical comparison using these numbers, which were given as examples; we did not give any p-value comparing Nevada and any of the seven states cited in Table 21. We thank Pinheiro and Jin for highlighting the erroneous total number of mesotheliomas in Table 21. Curiously, they also made a mistake: 31,408 + 133 = 31,541 instead of 31,545 as they stated. Pinheiro and Jin: “For the immediately younger (0–49) and older age groups (0–59) the risk in Nevada is fundamentally the same as in the US”, suggesting that only the 0–54 years-old group would be different. But their own Table 1 shows higher risk in Nevada for the 0–59 years old group, and higher risk in the 0–49 years old group for Southern Nevada, compared with the US. In addition, because of the small numbers, their 95% confidence intervals are large and do not allow for any significant comparison. Consequently, incidence/mortality rates clearly cannot be used to measure environmental exposures. Pinheiro and Jin graciously comment “We praise Baumann for producing a body of literature on mesothelioma and exposure to natural-occurring asbestos (NOA). The recent discovery of NOA in Southern Nevada has raised our interest in the surveillance of mesothelioma in the region”. So it appears we all agree that our findings identifying environmental exposure to asbestos in Southern Nevada are important and require follow up because asbestos causes mesothelioma. Therefore, we are puzzled by the title of their letter, a title that cannot be supported by data, and that in fact contradicts published evidence that exposure to asbestos increases the risk of mesothelioma and that such exposure is occurring in Southern Nevada8–10. Risk is defined as the product of hazard and vulnerability (or exposure)11. Southern Nevadans are indeed being exposed to the hazard of asbestos fibers and therefore are at increased risk for mesothelioma and other asbestos-related diseases1,12. For example, ambient air measured for Phase I of the Boulder City Bypass showed the presence of airborne asbestos fibers10. Moreover, some individuals may be exposed to significantly higher concentrations through recreational activities, such as off-road vehicle recreation, horseback riding, mountain bicycle riding, hiking, and other activities that are popular in the desert areas where asbestos fibers occur1,8–10,14. Environmental epidemiology is about identifying areas in which environmental risk exists and work with local experts and authorities to eliminate or at least mitigate the risk. We hope that we will be allowed to further investigate the areas in Southern Nevada where exposure occurs and where there is an apparent increase of mesothelioma among young adults. We would welcome the opportunity to work together with Nevada epidemiologists and the Nevada health authorities to help identify measures to reduce environmental exposure to asbestos and to other carcinogenic fibers and the consequent risk of mesothelioma, as we have done in other parts of the US and of the world6,14,15.