Nevada desert dust with heavy metals suppresses IgM antibody production

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 corre- sponding 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

Disruption of the Arsenic (+3 Oxidation State) Methyltransferase Gene in the Mouse Alters the Phenotype for Methylation of Arsenic and Affects Distribution and Retention of Orally Administered Arsenate

The arsenic (+3 oxidation state) methyltransferase (As3mt) gene encodes a 43 kDa protein that catalyzes methylation of inorganic arsenic. Altered expression of AS3MT in cultured human cells controls arsenic methylation phenotypes, suggesting a critical role in arsenic metabolism. Because methylated arsenicals mediate some toxic or carcinogenic effects linked to inorganic arsenic exposure, studies of the fate and effects of arsenicals in mice which cannot methylate arsenic could be instructive. This study compared retention and distribution of arsenic in As3mt knockout mice and in wild-type C57BL/6 mice in which expression of the As3mt gene is normal. Male and female mice of either genotype received an oral dose of 0.5 mg of arsenic as arsenate per kg containing [73As]-arsenate. Mice were radioassayed for up to 96 hours after dosing; tissues were collected at 2 and 24 hours after dosing. At 2 and 24 hours after dosing, livers of As3mt knockouts contained a greater proportion of inorganic and monomethylated arsenic than did livers of C57BL/6 mice. A similar predominance of inorganic and monomethylated arsenic was found in the urine of As3mt knockouts. At 24 hours after dosing, As3mt knockouts retained significantly higher percentages of arsenic dose in liver, kidneys, urinary bladder, lungs, heart, and carcass than did C57BL/6 mice. Whole body clearance of [73As] in As3mt knockouts was substantially slower than in C57BL/6 mice. At 24 hours after dosing, As3mt knockouts retained about 50% and C57BL/6 mice about 6% of the dose. After 96 hours, As3mt knockouts retained about 20% and C57BL/6 mice retained less than 2% of the dose. These data confirm a central role for As3mt in metabolism of inorganic arsenic and indicate that phenotypes for arsenic retention and distribution are markedly affected by the null genotype for arsenic methylation, indicating a close linkage between the metabolism and retention of arsenicals

Effects of Acute Aerobic and Resistance Exercise on Neuroplasticity- A Pilot Study

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Using stable carbon isotope ratio analysis to detect adulteration in red yeast rice dietary supplements

Red yeast rice (RYR) is marketed as a dietary supplement because it contains natural 3-hydroxy-3-methylglutaryl coenzyme A reductase inhibitors (statins), including monacolin K. However, there is concern that some RYR supplements may be adulterated with the pharmaceutical drug lovastatin to enhance health claims. We have developed an optimized method to isolate monacolin K/lovastatin from complex RYR dietary supplement matrices to then test for adulteration in RYR supplements using stable carbon isotope (δ13C) analysis. Samples were initially screened for monacolin K/lovastatin using liquid chromatography with mass spectrometric detection (LC-MS). To ensure the extraction process did not affect the measured isotopic values (i.e., isotopic fractionation effects), neat lovastatin standards were spiked into two types of blank RYR matrices (powder and gel). The monacolin K/lovastatin peaks were detected using high performance liquid chromatography with ultraviolet detection (HPLC-UV) and isolated using fraction collection. Residual matrix components were removed from targeted fractions by solid phase extraction (SPE) using graphitized carbon black cartridges. The resulting isolates were then analyzed using elemental analyzer-isotope ratio mass spectrometry (EA-IRMS) to measure δ13C values. The δ13C values of the extracted lovastatin standards were compared to their respective neat lovastatin δ13C values and demonstrated negligible isotopic fractionation effects. Using this optimized clean up method and carbon isotope analysis, thirty-one samples were screened. Eight RYR dietary supplement samples had >0.8 mg/g of monacolin K/lovastatin, our minimum threshold for analyzing samples using this method. Four of these eight samples had δ13C values greater than -28.3‰, a previously proposed cutoff value for natural monacolin K, indicating likely adulteration. Additionally, five RYR powder samples were analyzed as part of a collaborative study using in-house methods from two laboratories and the data shows acceptable agreement in the δ13C values of monacolin K/lovastatin (differences ranging from ±0.02‰ to ±0.76‰). This optimized method represents a robust, reproducible procedure for detecting lovastatin adulteration in dietary supplements with minimal isotopic fractionation

Matrix Extension and Multilaboratory Validation of Arsenic Speciation Method EAM §4.10 to Include Wine

A multilaboratory validation (MLV) was performed to extend the U.S. Food and Drug Administration’s (FDA) analytical method Elemental Analysis Manual (EAM) §4.10, <i>High Performance Liquid Chromatography-Inductively Coupled Plasma-Mass Spectrometric Determination of Four Arsenic Species in Fruit Juice</i>, to include wine. Several method modifications were examined to optimize the method for the analysis of dimethylarsinic acid, monomethylarsonic acid, arsenate (AsV), and arsenite (AsIII) in various wine matrices with a range of ethanol concentrations by liquid chromatography-inductively coupled plasma-mass spectrometry. The optimized method was used for the analysis of five wines of different classifications (red, white, sparkling, rosé, and fortified) by three laboratories. Additionally, the samples were fortified in duplicate at levels of approximately 5, 10, and 30 μg kg^–1 and analyzed by each participating laboratory. The combined average fortification recoveries of dimethylarsinic acid, monomethylarsonic acid, and inorganic arsenic (iAs the sum of AsV and AsIII) in these samples were 101, 100, and 100%, respectively. To further demonstrate the method, 46 additional wine samples were analyzed. The total As levels of all the wines analyzed in this study were between 1.0 and 38.2 μg kg^–1. The overall average mass balance based on the sum of the species recovered from the chromatographic separation compared to the total As measured was 89% with a range of 51–135%. In the 51 analyzed samples, iAs accounted for an average of 91% of the sum of the species with a range of 37–100%