A protocol for the prospective study of urinary cadmium with risk of fracture, bone loss, and muscle loss.

Cadmium (Cd) is a heavy metal and natural element found in soil and crops with increasing concentrations linked to phosphate fertilizers and sewage sludge applied to crop lands. A large fraction of older US men and woman have documented Cd exposure. Cd exposure has proven health concerns such as risk of lung cancer from inhalation and impaired renal function; however, growing evidence suggests it also influences bone and muscle health. Given that low levels of Cd could affect bone and muscle, we have designed prospective studies using the two largest and most detailed US studies of bone health in older men and women: the Osteoporotic Fractures in Men Study and the Study of Osteoporotic Fractures. We are investigating the association of urinary cadmium (U-Cd), as a surrogate for long-term Cd exposure, with bone and muscle health. Building off suggestive evidence from mechanistic and cross-sectional studies, this will be the first well-powered prospective study of incident fracture outcomes, bone loss, and muscle loss in relation to U-Cd, an established biomarker of long-term Cd exposure. The following is a proposed protocol for the intended study; if successful, the proposed studies could be influential in directing future US policy to decrease Cd exposure in the US population similar to recent policies adopted by the European Union to limit Cd in fertilizers.

Effect of Community Water Service on Lead in Drinking Water in an Environmental Justice Community.

Multiple recent studies have found elevated lead (Pb) concentrations in tap water in U.S. homes relying on unregulated private wells. The main Pb source is dissolution from household plumbing, fixtures, and well components. Here, we leverage a natural experiment and citizen science approach to evaluate how extending community water service to an environmental justice community relying on private wells affects Pb in household water. We analyzed Pb in 260 first-draw kitchen tap water samples collected by individual homeowners over a 5-month period in residences that did and did not connect to the community system. Before the community water system was extended, 25% of homes had Pb > 15 µg/L (the U.S. regulatory action level for community water systems) in first-draw water samples. Pb was significantly correlated with nickel (ρ = 0.61), zinc (ρ = 0.50), and copper (ρ = 0.40), suggesting that corrosion of brass fittings and fixtures is the main Pb source. Among homes that connected to the community system, Pb decreased rapidly and was sustained at levels well below 15 µg/L over the study period. Overall, connecting to the municipal water supply was associated with a 92.5% decrease in first-draw tap water Pb.

Urine antimony and risk of cardiovascular disease - A prospective case-cohort study in Danish Non-Smokers.

BACKGROUND: Limited evidence suggests that antimony induces vascular inflammation and oxidative stress and may play a role in cardiovascular disease (CVD) risk. However, few studies have examined whether environmental antimony from sources other than tobacco smoking is related with CVD risk. The general population may be exposed through air, drinking water, and food that contains antimony from natural and anthropogenic sources, such as mining, coal combustion, and manufacturing. OBJECTIVES: To examine the association of urine antimony with incident acute myocardial infarction (AMI), heart failure, and stroke among people who never smoked tobacco. METHODS: Between 1993 and 1997, the Danish Diet, Cancer and Health (DCH) cohort enrolled participants (ages 50-64 years), including n = 19,394 participants who reported never smoking at baseline. Among these never smokers, we identified incident cases of AMI (N = 809), heart failure (N = 958), and stroke (N = 534) using the Danish National Patient Registry. We also randomly selected a subcohort of 600 men and 600 women. We quantified urine antimony concentrations in samples provided at enrollment. We used modified Cox proportional hazards models to estimate adjusted hazard ratios (HR) for each incident CVD outcome in relation to urine antimony, statistically adjusted for creatinine. We used a separate prospective cohort, the San Luis Valley Diabetes Study (SLVDS), to replicate these results. RESULTS: In the DCH cohort, urine antimony concentrations were positively associated with rates of AMI and heart failure (HR = 1.52; 95%CI = 1.12, 2.08 and HR = 1.58; 95% CI = 1.15, 2.18, respectively, comparing participants in the highest (>0.09 µg/L) with the lowest quartile (<0.02 µg/L) of antimony). In the SLVDS cohort, urinary antimony was positively associated with AMI, but not heart failure. DISCUSSION: Among this sample of Danish people who never smoked, we found that low levels of urine antimony are associated with incident CVD. These results were partially confirmed in a smaller US cohort.

Short-term toxicity studies of thallium (I) sulfate administered in drinking water to Sprague Dawley rats and B6C3F1/N mice.

Thallium is a heavy metal that is known to induce a broad spectrum of adverse health effects in humans including alopecia, neurotoxicity, and mortality following high dose acute poisoning events. Widespread human exposure to thallium may occur via consumption of contaminated drinking water; limited toxicity data are available to evaluate the corresponding public health risk. To address this data gap, the Division of Translational Toxicology conducted short-term toxicity studies of a monovalent thallium salt, thallium (I) sulfate. Thallium (I) sulfate was administered via dosed drinking water to time-mated Sprague Dawley (Hsd:Sprague Dawley® SD®) rats (F0 dams) and their offspring (F1) from gestation day (GD) 6 until up to postnatal day (PND) 28 at concentrations of 0, 3.13, 6.25, 12.5, 25, or 50 mg/L, and adult male and female B6C3F1/N mice for up to 2 weeks at concentrations of 0, 6.25, 12.5, 25, 50, or 100 mg/L. Rat dams in the 50 mg/L exposure group were removed during gestation, and dams and offspring in the 25 mg/L exposure group were removed on or before PND 0 due to overt toxicity. Exposure to thallium (I) sulfate at concentrations ≤ 12.5 mg/L did not impact F0 dam body weights, maintenance of pregnancy, littering parameters, or F1 survival (PND 4-28). However, in F1 pups, exposure to 12.5 mg/L thallium (I) sulfate resulted in decreased body weight gains relative to control rats and onset of whole-body alopecia. Measurement of thallium concentrations in dam plasma, amniotic fluid, fetuses (GD 18), and pup plasma (PND 4) indicated marked maternal transfer of thallium to offspring during gestation and lactation. Mice exposed to 100 mg/L thallium (I) sulfate were removed early due to overt toxicity, and mice exposed to ≥ 25 mg/L exhibited exposure concentration-related decreases in body weight. Lowest-observed-effect levels of 12.5 mg/L (rats) and 25 mg/L (mice) were determined based on the increased incidence of clinical signs of alopecia in F1 rat pups and significantly decreased body weights for both rats and mice.

Validation of Analytical Method for Determination of Thallium in Rodent Plasma and Tissues by Inductively Coupled Plasma-Mass Spectrometry (ICP-MS).

Thallium (Tl) can be released as a byproduct of smelting, mining, and other industries, causing human exposure. There are knowledge gaps on the toxicity of thallium compounds, so the National Toxicology Program is investigating the toxicity of thallium (I) sulfate in rodents. We developed and validated a method to quantitate Tl in rodent plasma and secondary matrices. Primary matrix standards and validation samples were digested with nitric acid and analyzed for Tl by inductively-coupled plasma - mass spectrometry (ICP-MS). Method performance was validated for linearity, accuracy, precision, and other criteria. Calibration was linear from 1.25 to 500 ng Tl/mL plasma; accuracy (RE) was -5.9 to 2.6% for all calibration standards. The lower limit of quantitation (LLOQ) was 1.25 ng Tl/mL plasma, and the limit of detection was 0.0370 ng Tl/mL plasma. Intra- and interday RE and precision (RSD) were -5.6 to -1.7% and ≤0.8% (intraday) and -4.8 to -1.3% and ≤4.3% (interday), respectively, at three sample concentration levels. Standards up to 10.0 × 103 ng/mL could be analyzed by dilution with digested blank matrix, with -6.4% RE and 5.4% RSD. Method was also evaluated in post-natal day 4 (PND4) Hsd:Sprague Dawley SD (HSD) dam and pup plasma, gestation day 18 (GD 18) HSD rat fetal homogenate, HSD rat urine, female HSD rat brain homogenate, female B6C3F1 mouse plasma. Background Tl was detected in control fetal and brain homogenates and urine at < 30% of LLOQ response. Results demonstrate that the method is suitable for determination of Tl in rodent matrices for toxicology studies.

Adult Exposures to Toxic Trace Elements as Measured in Nails along the Interoceanic Highway in the Peruvian Amazon.

Deforestation, artisanal and small-scale gold mining (ASGM), and the rapid development related to highway expansion cause opportunities for toxic trace element exposure in the Amazon region of Madre de Dios (MDD), Peru, one of the most biologically diverse places in the world. The objective of this study was to assess the exposure to arsenic, cadmium, lead, and mercury among adults in Madre de Dios. In total, 418 adult (18+ years) participants in the Investigacion de Migracion, Ambiente, y Salud (IMAS) (Migration, Environment, and Health Study) participated in this study. Consent, survey data, and biospecimens were collected between August and November 2014. Nail elements were measured by inductively coupled plasma sector field mass spectrometry. Differences by selected individual and household characteristics and local land uses were tested using one-way ANOVAs and linear mixed models. Adults in ASGM-affected areas had higher nail arsenic and nail cadmium than their non-ASGM counterparts. Higher household fish consumption was positively associated with nail mercury and nail lead. The results indicate that adult exposure to arsenic, cadmium, lead, and mercury is heterogeneous across Madre de Dios, and the exposures related to ASGM communities and fish consumption suggest that exposures from artisanal and small-scale mining are environmentally widespread. Further investigation is warranted to ascertain potential health impacts.

Multidisciplinary Simulation Improves Resident Confidence for Pregnant Patients Requiring Surgical Intervention.

INTRODUCTION: Hepatocellular adenomas are a rare but serious cause of bleeding, which is further complicated by pregnancy. Interprofessional cooperation is a key component of residency education, thus simulations designed to integrate multiple programs are mutually beneficial. This simulation details surgical and obstetric management of a pregnant patient in hemorrhagic shock from a bleeding hepatocellular adenoma. Objectives for the study were to evaluate learners' confidence to 1) prioritize the care of a pregnant patient with hemoperitoneum and hemorrhagic shock, 2) demonstrate interdisciplinary collaboration with other specialties, 3) apply massive transfusion protocol (MTP) in the appropriate clinical setting, and 4) analyze critical decisions for evaluating pregnant females with severe abdominal pain. METHODS: Obstetric, general surgery, and anesthesia residents, along with labor and delivery nurses participated in a simulated clinical scenario that focused on the management of a pregnant patient in hemorrhagic shock. The learners evaluated the educational session using a standard Return on Investment in Learning survey immediately following the session. RESULTS: A total of 23 residents and medical students gave feedback on the experience. The main learning objectives were met with increased confidence in the four learning objectives by 77.3-95.4% of responders. Overall, greater than 90% of participants felt the simulation was relevant to their training and realistic, with 100% responding that the course provided new, or clarified existing information for them. CONCLUSION: A multidisciplinary simulation-based educational intervention was successful in improving learner confidence in managing a complicated surgical emergency in a pregnant patient with inter-residency cooperation.

Systemic exposure and urinary excretion of vanadium following perinatal subchronic exposure to vanadyl sulfate and sodium metavanadate via drinking water.

Vanadium is a ubiquitous environmental contaminant although there are limited data to assess potential adverse human health impact following oral exposure. In support of studies investigating the subchronic toxicity of vanadyl sulfate (V4+) and sodium metavanadate (V5+) following perinatal exposure via drinking water in male and female rats, we have determined the internal exposure and urinary excretion of total vanadium at the end of study. Water consumption decreased with increasing exposure concentration following exposure to both compounds. Plasma and urine vanadium concentration normalized to total vanadium consumed per day increased with the exposure concentration of vanadyl sulfate and sodium metavanadate suggesting absorption increased as the exposure concentration increased. Additionally, females had higher concentrations than males (in plasma only for vanadyl sulfate exposure). Animals exposed to sodium metavanadate had up to 3-fold higher vanadium concentration in plasma and urine compared to vanadyl sulfate exposed animals, when normalized to total vanadium consumed per day, demonstrating differential absorption, distribution, metabolism, and excretion properties between V5+ and V4+ compounds. These data will aid in the interpretation of animal toxicity data of V4+ and V5+ compounds and determine the relevance of animal toxicity findings to human exposures.

Variations in clot phenotype following injury: The MA-R ratio and fragile clots.

INTRODUCTION: Trauma-induced coagulopathy is a continuum ranging from hypercoagulable to hypercoagulable phenotypes. In single-center studies, the maximum amplitude (MA) to r-time (R) (MA-R) ratio has identified a phenotype of injured patients with high mortality risk. The purpose of this study was to determine the relationship between MA-R and mortality using multicenter data and to investigate fibrinogen consumption in the development of this specific coagulopathy phenotype. METHODS: Using the Pragmatic Randomized Optimal Platelet and Plasma Ratios data set, patients were divided into blunt and penetrating injury cohorts. MA was divided by R time from admission thromboelastogram to calculate MA-R. MA-R was used to assess odds of early and late mortality using multivariable models. Multivariable models were used to assess thrombogram values in both cohorts. Refinement of the MA-R cut point was performed with Youden index. Repeat multivariable analysis was performed with a binary CRITICAL and NORMAL MA-R. RESULTS: In initial analysis, MA-R quartiles were not associated with mortality in the penetrating cohort. In the blunt cohort, there was an association between low MA-R and early and late mortality. A refined cut point of 11 was identified (CRITICAL: MA-R, ≤11; NORMAL: MA-R, >11). CRITICAL MA-R was associated with mortality in both penetrating and blunt subgroups. In further injury subgroup analysis, CRITICAL patients had significantly decreased fibrinogen levels in the blunt subgroup only. In both blunt and penetrating injury, there was no difference in time to initiation of thrombin burst (lagtime). However, both endogenous thrombin potential and peak thrombin levels were significantly lower in CRITICAL patients. CONCLUSIONS: MA-R identifies a trauma-induced coagulopathy phenotype characterized in blunt injury by impaired thrombin generation that is associated with early and late mortality. The endotheliopathy and tissue factor release likely plays a role in the cascade of impaired thrombin burst, possible early fibrinogen consumption and the weaker clot identified by MA-R. LEVEL OF EVIDENCE: Therapeutic/care management, level II.

Urinary Cadmium and Incident Heart Failure: A Case-Cohort Analysis Among Never-Smokers in Denmark.

BACKGROUND: Epidemiologic studies suggest cadmium exposure is associated with cardiovascular disease risk, including heart failure. However, prior findings may be influenced by tobacco smoking, a dominant source of cadmium exposure and risk factor for heart failure. The present study leverages up to 20 years of follow-up in the Danish Diet, Cancer and Health cohort to examine the relationship between urinary cadmium and incident heart failure among people who never smoked. METHODS: Between 1993 and 1997, 19,394 never-smoking participants (ages 50-64 years) enrolled and provided a urine sample. From this sample, we randomly selected a subcohort of 600 men and 600 women and identified 958 incident heart failure cases occurring between baseline and 2015. Using a case-cohort approach, we estimated adjusted hazard ratios (aHR) for heart failure in Cox proportional hazards models with age as the time scale. RESULTS: Participants had relatively low concentrations of urinary cadmium, as expected for never smokers (median = 0.20; 25th, 75th = 0.13, 0.32 µg cadmium/g creatinine). In adjusted models, we found that higher urinary cadmium was associated with a higher rate of incident heart failure overall (aHR = 1.1 per interquartile range difference [95% CI = 1.0, 1.2). In sex-stratified analyses, the association seemed restricted to men (aHR = 1.5 [95% CI = 1.2, 1.9]). CONCLUSIONS: In this cohort of people who never smoked tobacco, environmental cadmium was positively associated with incident heart failure, especially among men.

Salicylate coordination in metal-protochelin complexes.

Molybdenum (Mo) is an essential trace element for bacteria that is utilized in myriad metalloenzymes that directly couple to the biogeochemical cycling of nitrogen, sulfur, and carbon. In particular, Mo is found in the most common nitrogenase enzyme, and the scarcity and low bioavailability of Mo in soil may be a critical factor that contributes to the limitation of nitrogen fixation in forests and agroenvironments. To overcome this scarcity, microbes produce exudates that specifically chelate scarce metals, promoting their solubilization and uptake. Here, we have determined the structure and stability constants of Mo bound by protochelin, a siderophore produced by bacteria under Mo-depleted conditions. Spectrophotometric titration spectra indicated a coordination shift from a catecholate to salicylate binding mode for MoVI-protochelin (Mo-Proto) complexes at pH < 5. pKa values obtained from analysis of titrations were 4.8 ± 0.3 for MoVIO2H3Proto- and 3.3 ± 0.1 for MoVIO2H4Proto. The occurrence of negatively charged Mo-Proto complexes at pH 6 was also confirmed by mass spectrometry. K-edge Extended X-ray absorption fine structure spectroscopy confirmed the change in Mo coordination at low pH, and structural fitting provides insights into the physical architecture of complexes at neutral and acidic pH. These findings suggest that Mo can be chelated by protochelin across a wide environmental pH range, with a coordination shift occurring at pH < 5. This chelation and associated coordination shift may impact biological availability and mineral surface retention of Mo under acidic conditions.

Quantitation of Total Vanadium in Rodent Plasma and Urine by Inductively Coupled Plasma - Mass Spectrometry (ICP-MS).

Human exposure to vanadium (V) is anticipated because it is a drinking water contaminant. Due to limited data on soluble V salts, the National Toxicology Program is investigating the toxicity in rodents following drinking water exposure. Measurement of internal V dose allows for interpretation of toxicology data. The objective of this study was to develop and validate an inductively coupled plasma-mass spectrometric method to quantitate total V in rat plasma. The method was linear (r ≥ 0.99) from 5.00 - 1,000 ng V/mL. Intra- and inter-day relative error (% RE) and relative standard deviation (% RSD) of spiked plasma samples were 8.5% - 15.6% RE and ≤ 1.8% RSD and 7.3% - 11.7% RE and ≤ 3.1% RSD, respectively. The limit of detection was 0.268 ng V/mL plasma and absolute percent recovery was 113%. Standards up to 7,500 ng V/mL plasma were diluted into the validated range (5.6% RE, 0.9% RSD). V in extracted plasma samples over 15 days at ambient and refrigerated conditions was from 97.7 - 126% of day 0. Determined plasma V concentrations after three freeze-thaw cycles and after frozen storage for up to 63 days ranged from 100 - 106% and 100 - 122% of day 0, respectively. The method was extended to rat urine (accuracy and precision -2.0 - 0.3% RE and <0.6% RSD, respectively for same linear range). These data demonstrate that the method is suitable to quantitate V in rat plasma and urine.

Relationship between Urine Creatinine and Urine Osmolality in Spot Samples among Men and Women in the Danish Diet Cancer and Health Cohort.

Assays of urine biomarkers often use urine creatinine to account for urinary dilution, even though creatinine levels are influenced by underlying physiology and muscle catabolism. Urine osmolality-a measure of dissolved particles including ions, glucose, and urea-is thought to provide a more robust marker of urinary dilution but is seldom measured. The relationship between urine osmolality and creatinine is not well understood. We calculated correlation coefficients between urine creatinine and osmolality among 1375 members of a subcohort of the Danish Diet, Cancer, and Health Cohort, and within different subgroups. We used linear regression to relate creatinine with osmolality, and a lasso selection procedure to identify other variables that explain remaining variability in osmolality. Spearman correlation between urine creatinine and osmolality was strong overall (ρ = 0.90; 95% CI: 0.89-0.91) and in most subgroups. Linear regression showed that urine creatinine explained 60% of the variability in urine osmolality, with another 9% explained by urine thallium (Tl), cesium (Cs), and strontium (Sr). Urinary creatinine and osmolality are strongly correlated, although urine Tl, Cs, and Sr might help supplement urine creatinine for purposes of urine dilution adjustment when osmolality is not available.

Urinary cadmium and stroke - a case-cohort study in Danish never-smokers.

BACKGROUND: and Purpose: Cadmium has been associated with risk of cardiovascular events, including stroke. Human cadmium exposure occurs primarily through diet and tobacco smoke. Recent cohort studies have found an association with stroke, but residual confounding from smoking, could not be ruled out. We therefore conducted a case-cohort study to evaluate whether cadmium is associated with stroke in never-smokers. METHODS: The Danish Diet Cancer and Health cohort consists of Danes 50-64 years old, recruited in 1993-1997. From never-smoking cohort members without previous cancer or stroke we sampled a sub-cohort of 1200 persons. We also identified all (n = 534) cases in the cohort with a validated stroke diagnosis between baseline and 2009. We quantified cadmium and creatinine concentrations from baseline urine samples and used cadmium per creatinine as our main exposure metric. We used Cox proportional hazards models to estimate hazard ratios (HRs) with age as time scale and adjusting for BMI, education and urinary cotinine with and without stratification by sex. RESULTS: The median urinary cadmium concentration was 0.21 µg cadmium/g creatinine in cases and 0.19 µg/g in the sub-cohort. The majority (83%) of stroke cases were diagnosed with ischemic stroke. The HR for stroke in the highest quartile of exposure (median 0.44 µg/g creatinine) was 1.11 (95% CI: 0.79-1.54) compared with the lowest quartile (median 0.10 µg/g creatinine). The HR per inter quartile range (IQR, 0.19 µg/g creatinine) was 1.02 (95% CI: 0.92-1.12). Among men, the HR per IQR higher levels of cadmium (0.16 µg/g creatinine) was 1.18 (95% CI: 0.92-1.52), and 1.00 (95% CI: 0.89-1.12) among women. Adjusting for creatinine or using osmolality instead of creatinine standardization generally attenuated observed relationships. CONCLUSIONS: Our results do not support that low levels of cadmium exposure among never-smokers are strongly associated with risk of stroke, although results varied somewhat by sex and method of accounting for urinary dilution.

Urine cadmium and acute myocardial infarction among never smokers in the Danish Diet, Cancer and Health cohort.

Cadmium exposure has been associated with cardiovascular disease. Cigarette smoking is a key source of cadmium exposure and thus a potential confounder in observational studies of environmental cadmium and cardiovascular disease that include tobacco smokers. We leveraged up to 20 years of follow-up in the Danish Diet, Cancer and Health cohort to test the hypothesis that cadmium exposure is associated with acute myocardial infarction (AMI) among people who never smoked. Between 1993 and 1997, 19,394 never-smoking participants (ages 50-64 years) were enrolled and provided a urine sample. From this sample, we randomly selected a subcohort of 600 males and 600 females. We identified 809 AMI cases occurring between baseline and the end of 2015 using the Danish National Patient Registry. We quantified cadmium, creatinine, and osmolality in baseline urine samples. Using an unweighted case-cohort approach, we estimated adjusted hazard ratios (aHR) for AMI in Cox proportional hazards models with age as the time axis. Participants had relatively low concentrations of urinary cadmium, as expected for never smokers (median = 0.20; 25th, 75th = 0.13, 0.32 µg cadmium/g creatinine). We did not find strong evidence to support an association between higher urinary cadmium and AMI when comparing the highest versus lowest quartile (aHR = 1.16; 95% CI: 0.86 - 1.56) and per IQR increment in cadmium concentration (aHR = 1.02; 95% CI: 0.93 - 1.12). Results were not materially different across strata defined by sex. Results were generally similar using creatinine or osmolality to account for differences in urine dilution. While cadmium exposure has been identified as a risk factor for cardiovascular disease, we did not find strong evidence that urinary cadmium at relatively low-levels is associated with AMI among people who have never smoked.

Constraints on the Coupling between Axionlike Dark Matter and Photons Using an Antiproton Superconducting Tuned Detection Circuit in a Cryogenic Penning Trap.

We constrain the coupling between axionlike particles (ALPs) and photons, measured with the superconducting resonant detection circuit of a cryogenic Penning trap. By searching the noise spectrum of our fixed-frequency resonant circuit for peaks caused by dark matter ALPs converting into photons in the strong magnetic field of the Penning-trap magnet, we are able to constrain the coupling of ALPs with masses around 2.7906-2.7914 neV/c^{2} to g_{aγ}<1×10^{-11} GeV^{-1}. This is more than one order of magnitude lower than the best laboratory haloscope and approximately 5 times lower than the CERN axion solar telescope (CAST), setting limits in a mass and coupling range which is not constrained by astrophysical observations. Our approach can be extended to many other Penning-trap experiments and has the potential to provide broad limits in the low ALP mass range.

Internal dose of vanadium in rats following repeated exposure to vanadyl sulfate and sodium orthovanadate via drinking water.

Vanadium is a ubiquitous environmental contaminant that exists in multiple oxidation states. Humans are exposed to vanadyl (V4+) and vanadate (V5+) from dietary supplements, food, and drinking water and hence there is a concern for adverse human health. The current investigation is aimed at identifying vanadium oxidation states in vitro and in vivo and internal concentrations following exposure of rats to vanadyl sulfate (V4+) or sodium metavanadate (V5+) via drinking water for 14 d. Investigations in simulated gastric and intestinal fluids showed that V4+ was stable in gastric fluid while V5+ was stable in intestinal fluid. Analysis of rodent plasma showed that the only vanadium present was V4+, regardless of the exposed compound suggesting conversion of V5+ to V4+ in vivo and/or instability of V5+ species in biological matrices. Plasma, blood, and liver concentrations of total vanadium, after normalizing for vanadium dose consumed, were higher in male and female rats following exposure to V5+ than to V4+. Following exposure to either V4+ or V5+, the total vanadium concentration in plasma was 2- to 3-fold higher than in blood suggesting plasma as a better matrix than blood for measuring vanadium in future work. Liver to blood ratios were 4-7 demonstrating significant tissue retention following exposure to both compounds. In conclusion, these data point to potential differences in absorption and disposition properties of V4+ and V5+ salts and may explain the higher sensitivity in rats following drinking water exposure to V5+ than V4+ and highlights the importance of internal dose determination in toxicology studies.

A population-based mercury exposure assessment near an artisanal and small-scale gold mining site in the Peruvian Amazon.

Human exposure to mercury is a leading public health problem. Artisanal and small-scale gold mining (ASGM) is a major source of global mercury emissions. Although occupational mercury exposure to miners (via mercury vapor inhalation) is known, chronic mercury exposure to nearby residents that are not miners (via mercury-contaminated fish consumption) is poorly characterized. We conducted a population-based mercury exposure assessment in 23 communities (19 rural, 4 urban) around the Amarakaeri Communal Reserve, which is bordered on the east by heavy ASGM activity. We measured total mercury in hair (N = 2083) and blood (N = 476) from March-June 2015 and performed follow-up measurements (N = 723 hair and N = 290 blood) from February-April 2016. Mercury exposure risk was highest in communities classified as indigenous, or native, regardless of proximity to mining activity. Residence in a native community (vs. non-native) was associated with mercury levels 1.9 times higher in hair (median native 3.5 ppm vs. median non-native 1.4 ppm total mercury) and 1.6 times higher in blood (median native 7.4 ng/mL vs median non-native 3.2 ng/mL total mercury). Unexpectedly, proximity to mining was not associated with exposure risk. These findings challenge common assumptions about mercury exposure patterns and emphasize the importance of population-representative studies to identify high risk sub-populations.