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1.
Toxicol Rep ; 5: 258-269, 2018.
Article in English | MEDLINE | ID: mdl-29854597

ABSTRACT

Systemic health effects from exposure to a complex natural dust containing heavy metals from the Nellis Dunes Recreation Area (NDRA) near Las Vegas, NV, were evaluated. Several toxicological parameters were examined following lung exposure to emissive dust from three geologic sediment types heavily used for recreational off-road activities: yellow sand very rich in arsenic (termed CBN 5); a shallow cover of loose dune sand overlying a gravelly subsoil bordering dune fields (termed CBN 6); and brown claystone and siltstone (termed CBN 7). Adult female B6C3F1 mice were exposed by oropharyngeal administration to these three types of geogenic dusts at 0.01-100 mg of dust/kg of body weight, once per week for four weeks. The median grain sizes were 4.6, 3.1, and 4.4 µm, for CBN 5, 6, and 7, respectively. Each type of dust contained quantifiable amounts of aluminum, vanadium, chromium, manganese, iron, cobalt, copper, zinc, arsenic, strontium, cesium, lead, uranium, and others. Descriptive markers of immunotoxicity, neurotoxicity, hematology, and clinical chemistry parameters were assessed. Notable among all three CBN units was a systemic, dose-responsive decrease in antigen-specific IgM antibody responses. Geogenic dust from CBN 5 produced more than a 70% suppression in IgM responses, establishing a lowest adverse effect level (LOAEL) of 0.01 mg/kg. A suppression in IgM responses and a corresponding increase in serum creatinine determined a LOAEL of 0.01 mg/kg for CBN 6. The LOAEL for CBN 7 was 0.1 mg/kg and also was identified from suppression in IgM responses. These results are of concern given the frequent off-road vehicle traffic and high visitor rates at the NDRA, estimated at 300,000 each year.

2.
Toxicol Rep ; 4: 19-31, 2017.
Article in English | MEDLINE | ID: mdl-28959621

ABSTRACT

The specific health effects of direct inhalation of fine minerogenic dusts generated by natural soil surfaces remain poorly known and relatively little researched. To learn more about this exposure and its contribution to human health effects, we surveyed surface sediment and characterized dust from the Nellis Dunes Recreation Area (NDRA) in Clark County, Nevada, a popular off-road vehicle (ORV) recreational site. Dry drainage systems at NDRA are commonly used as natural trail systems for ORV recreation; these surfaces also are characterized by high concentrations of heavy metals. Geogenic dust with a median diameter of 4.05 µm, collected from drainage surfaces at NDRA contained a total elemental concentration of aluminum (79,651 µg/g), vanadium (100 µg/g), chromium (54 µg/g), manganese (753 µg/g), iron (33,266 µg/g), cobalt (14 µg/g), copper (37 µg/g) zinc (135 µg/g), arsenic (71 µg/g), strontium (666 µg/g), cesium (15 µg/g), lead (34 µg/g), and uranium (54.9 µg/g). Adult female B6C3F1 mice exposed via oropharyngeal aspiration to 0.01-100 mg dust/kg body weight, four times, a week apart, for 28-days, were evaluated for immuno- and neurotoxicological outcomes 24 h after the last exposure. Antigen-specific IgM responses were dose-responsively suppressed at 0.1, 1.0, 10 and 100 mg/kg. Splenic lymphocytic subpopulations, hematological and clinical chemistry parameters were affected. In brain tissue, antibodies against NF-68, and GFAP were not affected, whereas IgM antibodies against MBP were reduced by 26.6% only in the highest dose group. A lowest observed adverse effect level (LOAEL) of 0.1 mg/kg/day and a no observed adverse effect level (NOAEL) of 0.01 mg/kg/day were derived based on the antigen primary IgM responses after subacute exposure to this geogenic dust.

3.
J Toxicol Environ Health B Crit Rev ; 19(5-6): 213-230, 2016.
Article in English | MEDLINE | ID: mdl-27705545

ABSTRACT

Similar to asbestos fibers, nonregulated mineral fibers can cause malignant mesothelioma (MM). Recently, increased proportions of women and young individuals with MM were identified in southern Nevada, suggesting that environmental exposure to carcinogenic fibers was causing the development of MM. Palygorskite, a fibrous silicate mineral with a history of possible carcinogenicity, is abundant in southern Nevada. In this study, our aim was to determine whether palygorskite was contributing to the development of MM in southern Nevada. While palygorskite, in vitro, displayed some cytotoxicity toward primary human mesothelial (HM) cells and reduced their viability, the effects were roughly half of those observed when using similar amounts of crocidolite asbestos. No Balb/c (0/19) or MexTAg (0/18) mice injected with palygorskite developed MM, while 3/16 Balb/c and 13/14 MexTAg mice injected with crocidolite did. Lack of MM development was associated with a decreased acute inflammatory response, as injection of palygorskite resulted in lower percentages of macrophages (p = .006) and neutrophils (p = .02) in the peritoneal cavity 3 d after exposure compared to injection of crocidolite. Additionally, compared to mice injected with crocidolite, palygorskite-injected mice had lower percentages of M2 (tumor-promoting) macrophages (p = .008) in their peritoneal cavities when exposed to fiber for several weeks. Our study indicates that palygorskite found in the environment in southern Nevada does not cause MM in mice, seemingly because palygorskite, in vivo, fails to elicit inflammation that is associated with MM development. Therefore, palygorskite is not a likely contributor to the MM cases observed in southern Nevada.


Subject(s)
Epithelial Cells/drug effects , Lung Neoplasms/pathology , Magnesium Compounds/toxicity , Mesothelioma/pathology , Silicon Compounds/toxicity , Animals , Epithelial Cells/cytology , Lung Neoplasms/chemically induced , Mesothelioma/chemically induced , Mesothelioma, Malignant , Mice , Mice, Inbred BALB C , Nevada
4.
Toxicol Appl Pharmacol ; 304: 79-89, 2016 08 01.
Article in English | MEDLINE | ID: mdl-27221630

ABSTRACT

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.


Subject(s)
Arsenic/toxicity , Dust/immunology , Animals , Arsenic/analysis , Blood Urea Nitrogen , Body Weight/drug effects , Complex Mixtures , Creatinine/blood , Dose-Response Relationship, Drug , Dust/analysis , Eosinophils/drug effects , Female , Immunoglobulin M/drug effects , Immunophenotyping , Killer Cells, Natural/drug effects , Mice , Neurofilament Proteins/immunology , Nevada , Organ Size/drug effects , Particle Size , Spleen/pathology
5.
Toxicol Appl Pharmacol ; 291: 1-12, 2016 Jan 15.
Article in English | MEDLINE | ID: mdl-26644169

ABSTRACT

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.


Subject(s)
Air Pollutants/immunology , Air Pollutants/toxicity , Dust/immunology , Particulate Matter/immunology , Particulate Matter/toxicity , Recreation , Animals , Environmental Exposure/adverse effects , Female , Killer Cells, Natural/immunology , Metals/immunology , Metals/toxicity , Mice , Mice, Inbred C57BL , Nevada , T-Lymphocytes, Regulatory/immunology , Toxicity Tests, Subacute/methods
6.
Toxicol Rep ; 3: 785-795, 2016.
Article in English | MEDLINE | ID: mdl-28959605

ABSTRACT

Desert areas are usually characterized by a continuous deposition of fine airborne particles. Over time, this process results in the accumulation of silt and clay on desert surfaces. We evaluated health effects associated with regional atmospheric dust, or geogenic dust, deposited on surfaces in the Nellis Dunes Recreation Area (NDRA) in Clark County, Nevada, a popular off-road vehicle (ORV) recreational site frequented daily by riders, families, and day campers. Because of atmospheric mixing and the mostly regional origin of the accumulated particles, the re-suspended airborne dust is composed of a complex mixture of minerals and metals including aluminum, vanadium, chromium, manganese, iron, cobalt, copper, zinc, arsenic, strontium, cesium, lead, uranium, and others. Geogenic dust with a median diameter of 4.1 µm was administered via oropharyngeal aspiration to female B6C3F1 mice at doses of 0.01 to 100 mg dust/kg body weight, four times, a week apart, for 28-days. Immuno- and neurotoxicological outcomes 24 h following the last exposure were evaluated. Antigen-specific IgM responses were dose-responsively suppressed at 0.1, 1.0, 10 and 100 mg/kg/day. Splenic and thymic lymphocytic subpopulations and natural killer cell activity also were significantly reduced. Antibodies against MBP, NF-68, and GFAP were not affected, while brain CD3+ T cells were decreased in number. A lowest observed adverse effect level (LOAEL) of 0.1 mg/kg/day and a no observed adverse effect level (NOAEL) of 0.01 mg/kg/day were derived based on the antigen-specific IgM responses.

8.
PLoS One ; 10(4): e0124271, 2015.
Article in English | MEDLINE | ID: mdl-25897667

ABSTRACT

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.


Subject(s)
Air Pollutants/analysis , Arsenic/analysis , Soil Pollutants/analysis , Humans , Nevada , Parks, Recreational , Risk Assessment
9.
J Thorac Oncol ; 10(5): 731-737, 2015 May.
Article in English | MEDLINE | ID: mdl-25668121

ABSTRACT

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.


Subject(s)
Asbestos/analysis , Environmental Exposure/analysis , Inhalation Exposure , Mesothelioma/epidemiology , Age Factors , Female , Geology , Humans , Incidence , Male , Mesothelioma/mortality , Middle Aged , Nevada/epidemiology , Sex Factors , Weather
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