Although exposure to metals remains a public health concern, few studies have examined exposure to combinations of metals. This study characterized prevalent combinations of cadmium (Cd), mercury (Hg), and lead (Pb) in women (n = 10,152; aged 20-44 years) who participated in the U.S. National Health and Nutrition Examination Survey (NHANES) 1999-2018. To explore relative metal exposures within this population, Cd, Hg, and Pb blood levels were dichotomized as "high" and "low" categories using median values to represent the center of the metal concentrations in the study population, not thresholds for adverse health effects. The prevalence of the three metal combinations at "high" levels (singular, binary, tertiary combinations) was calculated. Multinomial logistic regression was used to calculate odds ratios for each combination relative to none of these combinations after adjusting for potential confounders. Among the pregnant women (n = 1297), singular Hg was most prevalent (19.2% [95% CI 15.0-23.3]), followed by singular Cd (14.7% [95% CI 11.2-18.2]), tertiary combination Cd/Hg/Pb (11.0% [95% CI 8.7-13.2]), binary combinations Cd/Pb (9.8% [95% CI 7.4-12.2]), Hg/Pb (9.2% [95% CI 6.5-11.8]), Cd/Hg (7.8% [95% CI 6.0-9.6]), and singular Pb (5.5% [95% CI 4.1-6.9]). We found significantly lower odds of having Cd/Hg/Pb (adjusted odds ratio (adjOR) = 0.49: p < 0.001) and Cd/Pb (adjOR = 0.68: p < 0.0364) combinations among pregnant women compared to non-pregnant women. The odds of having higher levels of singular Pb were significantly lower (adjOR = 0.31: p < 0.0001) in women pregnant in their first and second trimesters (n = 563) than in non-pregnant women (n = 6412), whereas, though nonsignificant, the odds were higher for women pregnant in their third trimester (n = 366) (adjOR = 1.25: p = 0.4715). These results indicate the possibility that the fetus might be exposed to higher levels of the metal mixtures due to placental transfer, particularly to Pb, during the early stages of pregnancy. Further research is warranted to understand the relationship between metal combination exposures during pregnancy and maternal and infant health.

The Centers for Disease Control and Prevention (CDC) Radiation Laboratory’s primary mission is to provide laboratory support for an effective and efficient response to public health radiological emergencies. The laboratory has developed methods for several radiological threat agents, including Iridium-192 (Ir-192). Ir-192 can be analyzed via its gamma energy through analytical methods such as High Purity Germanium (HPGe) and its beta energy through Liquid Scintillation Counting (LSC). In this work, we present and compare HPGe and LSC rapid response methods for Ir-192 quantification. Both methods show the reasonable results and can be used in emergency situations. © This is a U.S. Government work and not under copyright protection in the US; foreign copyright protection may apply 2024.

BACKGROUND: The reduction in cardiovascular disease (CVD) events with edetate disodium (EDTA) in the Trial to Assess Chelation Therapy (TACT) suggested that chelation of toxic metals might provide novel opportunities to reduce CVD in patients with diabetes. Lead and cadmium are vasculotoxic metals chelated by EDTA. We present baseline characteristics for participants in TACT2, a randomized, double-masked, placebo-controlled trial designed as a replication of the TACT trial limited to patients with diabetes. METHODS: TACT2 enrolled 1,000 participants with diabetes and prior myocardial infarction, age 50 years or older between September 2016 and December 2020. Among 959 participants with at least one infusion, 933 had blood and/or urine metals measured at the Centers for Diseases Control and Prevention using the same methodology as in the National Health and Nutrition Examination Survey (NHANES). We compared metal levels in TACT2 to a contemporaneous subset of NHANES participants with CVD, diabetes and other inclusion criteria similar to TACT2's participants. RESULTS: At baseline, the median (interquartile range, IQR) age was 67 (60, 72) years, 27% were women, 78% reported white race, mean (SD) BMI was 32.7 (6.6) kg/m(2), 4% reported type 1 diabetes, 46.8% were treated with insulin, 22.3% with GLP1-receptor agonists or SGLT-2 inhibitors, 90.2% with aspirin, warfarin or P2Y12 inhibitors, and 86.5% with statins. Blood lead was detectable in all participants; median (IQR) was 9.19 (6.30, 13.9) μg/L. Blood and urine cadmium were detectable in 97% and median (IQR) levels were 0.28 (0.18, 0.43) μg/L and 0.30 (0.18, 0.51) μg/g creatinine, respectively. Metal levels were largely similar to those in the contemporaneous NHANES subset. CONCLUSIONS: TACT2 participants were characterized by high use of medication to treat CVD and diabetes and similar baseline metal levels as in the general US population. TACT2 will determine whether chelation therapy reduces the occurrence of subsequent CVD events in this high-risk population. CLINICAL TRIALS REGISTRATION: ClinicalTrials.gov. Identifier: NCT02733185. https://clinicaltrials.gov/study/NCT02733185.

Liquid Scintillation Counting (LSC) gross alpha/beta screening is a valuable tool for providing rapid laboratory response for the analysis of human clinical urine samples during a large-scale radiation incident event. Verification of method performance, as required for clinical laboratory testing, is accomplished by the evaluation of routine, periodic measurements of radioactive spiked samples for quality control, performance testing, and accuracy checks. Radionuclide stability of alpha and beta emitters in urine for LSC analysis is an important consideration. The purpose of this work is to demonstrate optimal preparations and storage conditions of samples used for method verification. © This is a U.S. Government work and not under copyright protection in the US; foreign copyright protection may apply 2024.

INTRODUCTION: Concurrent use of tobacco cigarettes and e-cigarettes ("dual use") is common among tobacco users. Little is known about differences in demographics and toxicant exposure among subsets of dual users. AIMS AND METHODS: We analyzed data from adult dual users (current every/some day users of tobacco cigarettes and e-cigarettes, n = 792) included in the PATH Study Wave 1 (2013-2014) and provided urine samples. Samples were analyzed for biomarkers of exposure to nicotine and selected toxicants (tobacco-specific nitrosamine NNK [NNAL], lead, cadmium, naphthalene [2-naphthol], pyrene [1-hydroxypyrene], acrylonitrile [CYMA], acrolein [CEMA], and acrylamide [AAMA]). Subsets of dual users were compared on demographic, behavioral, and biomarker measures to exclusive cigarette smokers (n = 2411) and exclusive e-cigarette users (n = 247). RESULTS: Most dual users were predominant cigarette smokers (70%), followed by daily dual users (13%), non-daily concurrent dual users (10%), and predominant vapers (7%). Dual users who smoked daily showed significantly higher biomarker concentrations compared with those who did not smoke daily. Patterns of e-cigarette use had little effect on toxicant exposure. Dual users with high toxicant exposure were generally older, female, and smoked more cigarettes per day. Dual users who had low levels of biomarkers of exposure were generally younger, male, and smoked non-daily. CONCLUSIONS: In 2013-2014, most dual users smoked cigarettes daily and used e-cigarettes occasionally. Cigarette smoking appears to be the primary driver of toxicant exposure among dual users, with little-to-no effect of e-cigarette use on biomarker levels. Results reinforce the need for dual users to stop smoking tobacco cigarettes to reduce toxicant exposure. IMPLICATIONS: With considerable dual use of tobacco cigarettes and e-cigarettes in the United States, it is important to understand differences in toxicant exposure among subsets of dual users, and how these differences align with user demographics. Findings suggest most dual users smoke daily and use e-cigarettes intermittently. Low exposure to toxicants was most common among younger users, males, and intermittent smokers; high exposure to toxicants was most common among older users, females, and heavier cigarette smokers. Results underscore the heterogeneity occurring within dual users, and the need to quit smoking cigarettes completely in order to reduce toxicant exposure.

A number of errors with potentially significant consequences may be introduced at various points in the analytical process which result in skewed, erroneous analytical results. Precautionary procedures such as contamination control, following established sample collection protocols, and having a complete understanding of the long-term stability of the elements of interest can minimize or eliminate these errors. Contamination control is critical in quantification of Cr and Co in human whole blood. Cr and Co levels in most biological samples are low, but these elements occur naturally in the environment and are often found in commercial and consumer products, which increases the risk of contamination. In this paper, we demonstrated that lot screening process in which we pre-screen a sub-set of manufactured lots used in collecting, analyzing, and storing blood samples is a critical step in controlling Cr and Co contamination. Stainless steel needles are often utilized in blood collection but are considered a potential source of introducing metal contamination to the patient sample. We conducted two studies to determine if there is a possibility of Cr or Co leaching into the human whole blood from the needles during blood collection. We analyzed blood collected from 100 donors and blood collected in-vitro in the laboratory from designated vessel containing spiked blood with higher levels of Cr and Co. Two blood tubes were consecutively collected through one needle. In both studies, Cr and Co concentration levels in the two consecutively collected tubes were compared. Based on the results from donor and in-vitro blood collection studies, we concluded there was no Cr and Co leaching from the limited sets of stainless steel needles used in these studies. Further, we demonstrated that Cr and Co human whole blood samples are stable for one year stored at temperatures of -70 degrees C, -20 degrees C, and 4 degrees C, and six months at room temperature.

BACKGROUND: Monitoring population-level toxicant exposures from smokeless tobacco (SLT) use is important for assessing population health risks due to product use. In this study, we assessed tobacco biomarkers of exposure (BOEs) among SLT users from the Wave 1 (2013-14) of the Population Assessment of Tobacco and Health (PATH) Study. METHODS: Urinary biospecimens were collected from adults aged 18 and older. Biomarkers of nicotine, tobacco-specific nitrosamines (TSNAs), polycyclic aromatic hydrocarbons (PAHs), volatile organic compounds (VOCs), metals, and inorganic arsenic were analyzed and reported among exclusive current established SLT users in comparison to exclusive current established cigarette smokers, dual SLT and cigarette users, and never tobacco users. RESULTS: In general, SLT users (n=448) have significantly higher concentrations of biomarkers of exposure to nicotine, TSNAs and PAHs compared to never tobacco users; significant dose-response relationships between frequency of SLT use and biomarker concentrations were also reported among exclusive SLT daily users. Exclusive SLT daily users have higher geometric mean concentrations of total nicotine equivalent-2 (TNE2) and TSNAs than exclusive cigarette daily smokers. In contrast, geometric mean concentrations of PAHs and VOCs were substantially lower among exclusive SLT daily users than exclusive cigarette daily smokers. CONCLUSIONS: Our study produced a comprehensive assessment of SLT product use and 52 biomarkers of tobacco exposure. Compared to cigarette smokers, SLT users experience greater concentrations of some tobacco toxicants, including nicotine and TSNAs. IMPACT: Our data add information on the risk assessment of exposure to SLT-related toxicants. High levels of harmful constituents in SLT remain a health concern.

In July 2019, a Mexican-American woman aged 47 years in Sacramento, California, sought medical care for dysesthesias and weakness of her upper extremities. Over the ensuing 2 weeks of outpatient follow-up, her condition progressed to dysarthria, blurry vision, and gait unsteadiness, leading to hospital admission. While hospitalized, her condition declined rapidly to an agitated delirium. Two weeks into the hospitalization, screening blood and urine tests detected mercury concentrations exceeding the upper limit (UL) of quantification, indicative of abnormally high values of mercury (>160 μg/L [blood] and >80 μg/L [urine]). The hospital notified the California Poison Control System (CPCS) and the California Department of Public Health (CDPH). CPCS recommended oral dimercaptosuccinic acid, 10 mg/kg every 8 hours, which was administered via feeding tube. CDPH interviewed the patient’s family and learned that the patient was a long-term user of skin lightening creams obtained from Mexico (applied to the face twice daily for the past 7 years); the cream was analyzed and found to contain 12,000 ppm mercury. Mercury levels from the hospital specimens that initially implicated mercury were 2,620 μg/L blood mercury (reference population UL <1.81 μg/L)* and 110 μg/L urine mercury (UL <0.90 μg/L). A second blood specimen collected 11 days after the hospital initiation of ongoing dimercaptosuccinic acid chelation therapy detected 1,114 μg/L mercury.

The Centers for Disease Control and Prevention’s (CDC) Environmental Health Laboratory uses modified versions of inductively coupled plasma mass spectrometry (ICP-MS) analytical methods to quantify metals contamination present in items that will come into contact with patient samples during the preanalytical, analytical, and postanalytical stages. This lot screening process allows us to reduce the likelihood of introducing contamination which can lead to falsely elevated results. This is particularly important when looking at biomonitoring levels in humans which tend to be near the limit of detection of many methods. The fundamental requirements for a lot screening program in terms of facilities and processes are presented along with a discussion of sample preparation techniques used for lot screening. The criteria used to evaluate the lot screening data to determine the acceptability of a particular manufacturing lot is presented as well. As a result of lot testing, unsuitable manufactured lots are identified and excluded from use.

Declining response rates may introduce bias into survey results and increase costs. Two national surveys, the National Immunization Survey (NIS) and the NIS-Teen, were used to study the impact of survey length, as stated by the interviewer, and inclusion of a topic of interest to respondents on response rates. The two studies included comparisons of the standard survey instruments to revised, condensed instruments. The NIS study also included variations of the standard survey with sections considered of interest for parental respondents, the Parental Concerns Module (PCM), which contained questions about parents' thoughts and beliefs about vaccinations. The outcomes of interest were differences in the response rates and resulting survey costs in each of the study conditions. The shortened instruments resulted in higher response rates compared to both the standard instruments and the instruments including the PCM and reduced the overall time needed to complete an interview. Based on these results, the NIS and NIS-Teen questionnaires were both shortened.

In 2012, the Centers for Disease Control and Prevention (CDC) adopted its Advisory Committee on Childhood Lead Poisoning Prevention recommendation to use a population-based reference value to identify children and environments associated with lead hazards. The current reference value of 5 mug/dL is calculated as the 97.5th percentile of the distribution of blood lead levels (BLLs) in children 1 to 5 years old from 2007 to 2010 NHANES data. We calculated and updated selected percentiles, including the 97.5th percentile, by using NHANES 2011 to 2014 blood lead data and examined demographic characteristics of children whose blood lead was ≥90th percentile value. The 97.5th percentile BLL of 3.48 microg/dL highlighted analytical laboratory and clinical interpretation challenges of blood lead measurements ≤5 mug/dL. Review of 5 years of results for target blood lead values <11 microg/dL for US clinical laboratories participating in the CDC's voluntary Lead and Multi-Element Proficiency quality assurance program showed 40% unable to quantify and reported a nondetectable result at a target blood lead value of 1.48 microg/dL, compared with 5.5% at a target BLL of 4.60 microg/dL. We describe actions taken at the CDC's Environmental Health Laboratory in the National Center for Environmental Health, which measures blood lead for NHANES, to improve analytical accuracy and precision and to reduce external lead contamination during blood collection and analysis.

The Centers for Disease Control and Prevention developed a biomonitoring method to rapidly and accurately quantify chromium and cobalt in human whole blood by ICP-MS. Many metal-on-metal hip implants which contain significant amounts of chromium and cobalt are susceptible to metal degradation. This method is used to gather population data about chromium and cobalt exposure of the U.S. population that does not include people that have metal-on-metal hip implants so that reference value can be established for a baseline level in blood. We evaluated parameters such as; helium gas flow rate, choice and composition of the diluent solution for sample preparation, and sample rinse time to determine the optimal conditions for analysis. The limits of detection for chromium and cobalt in blood were determined to be 0.41 and 0.06 g L-1, respectively. Method precision, accuracy, and recovery for this method were determined using quality control material created in-house and historical proficiency testing samples. We conducted experiments to determine if quantitative changes in the method parameters affect the results obtained by changing four parameters while analyzing human whole blood spiked with National Institute of Standard and Technology traceable materials: the dilution factor used during sample preparation, sample rinse time, diluent composition, and kinetic energy discrimination gas flow rate. The results at the increased and decreased levels for each parameter were statistically compared to the results obtained at the optimized parameters. We assessed the degree of reproducibility obtained under a variety of conditions and evaluated the method's robustness by analyzing the same set of proficiency testing samples by different analysts, on different instruments, with different reagents, and on different days. The short-term stability of chromium and cobalt in human blood samples stored at room temperature was monitored over a time period of 64 hours by diluting and analyzing samples at different time intervals. The stability of chromium and cobalt post-dilution was also evaluated over a period of 48 hours and at two storage temperatures (room temperature and refrigerated at 4 C). The results obtained during the stability studies showed that chromium and cobalt are stable in human blood for a period of 64 hours. The Royal Society of Chemistry 2017.

In this study, we evaluated the effect of temperature on the long-term stability of three mercury species in bovine blood. We used inductively coupled plasma mass spectrometry (ICP-MS) analysis to determine the concentrations of inorganic (iHg), methyl (MeHg) and ethyl (EtHg) mercury species in two blood pools stored at temperatures of -70, -20, 4, 23 degrees C (room temperature) and 37 degrees C. Over the course of a year, we analyzed aliquots of pooled specimens at time intervals of 1, 2, 4 and 6 weeks and 2, 4, 6, 8, 10 and 12 months. We applied a fixed-effects linear model, step-down pairwise comparison and coefficient of variation statistical analysis to examine the temperature and time effects on changes in mercury species concentrations. We observed several instances of statistically significant differences in mercury species concentrations between different temperatures and time points; however, with considerations of experimental factors (such as instrumental drift and sample preparation procedures), not all differences were scientifically important. We concluded that iHg, MeHg and EtHg species in bovine whole blood were stable at -70, -20, 4 and 23 degrees C for 1 year, but blood samples stored at 37 degrees C were stable for no more than 2 weeks.

BACKGROUND: Despite the public health and toxicologic interest in methyl mercury (MeHg) and ethyl mercury (EHg), these mercury species have been technically difficult to measure in large population studies. METHODS: Using NHANES 2011-2012 data, we calculated reference ranges and examined demographic factors associated with specific mercury species concentrations and the ratio of MeHg to THg. We conducted several multiple regression analyses to examine factors associated with MeHg concentrations and also with the ratio of MeHg to THg. RESULTS: Asians had the highest geometric mean concentrations for MeHg, 1.58microg/L (95% CI 1.29, 1.93) and THg, 1.86microg/L (1.58, 2.19), followed by non-Hispanic blacks with MeHg, 0.52microg/L (0.39, 0.68) and THg, 0.68microg/L (0.54, 0.85). Greater education attainment in adults and male sex were associated with higher MeHg and THg concentrations. Race/ethnicity, age, and sex were significant predictors of MeHg concentrations, which increased with age and were highest in Asians in all age categories, followed by non-Hispanic blacks. Mexican Americans had the lowest adjusted MeHg concentrations. The ratio of MeHg to THg was highest in Asians, varied by racial/ethnic group, and increased with age in a non-linear fashion. The amount of increase in the MeHg to THg ratio with age depended on the initial ratio, with a greater increase as age increased. Of the overall population, 3.05% (95% CI 1.77, 4.87) had MeHg concentrations >5.8microg/L (a value that corresponds to the U.S. EPA reference dose). The prevalence was highest in Asians at 15.85% (95% CI 11.85, 20.56), increased with age, reaching a maximum of 9.26% (3.03, 20.42) at ages 60-69 years. Females 16-44 years old had a 1.76% (0.82-3.28) prevalence of MeHg concentrations >5.8microg/L. CONCLUSIONS: Asians, males, older individuals, and adults with greater educational attainment had higher MeHg concentrations. The ratio of MeHg to THg varied with racial/ethnic group, increased with age, and was nonlinear. U.S. population reference values for MeHg and the ratio of MeHg to THg can assist in more precise assessment of public health risk from MeHg consumed in seafood.

The measurement of different mercury compounds in human blood can provide valuable information about the type of mercury exposure. To this end, our laboratory developed a biomonitoring method for the quantification of inorganic (iHg), methyl (MeHg), and ethyl (EtHg) mercury in whole blood using a triple-spike isotope dilution (TSID) quantification method employing capillary gas chromatography (GC) and inductively coupled dynamic reaction cell mass spectrometry (ICP-DRC-MS). We used a robotic CombiPAL(R) sample handling station featuring twin fiber-based solid-phase microextraction (SPME) injector heads. The use of two SPME fibers significantly reduces sample analysis cycle times making this method very suitable for high sample throughput, which is a requirement for large public health biomonitoring studies. Our sample preparation procedure involved solubilization of blood samples with tetramethylammonium hydroxide (TMAH) followed by the derivatization with sodium tetra(n-propyl)borate (NaBPr4) to promote volatility of mercury species. We thoroughly investigated mercury species stability in the blood matrix during the course of sample treatment and analysis. The method accuracy for quantifying iHg, MeHg, and EtHg was validated using NIST standard reference materials (SRM 955c level 3) and the Centre de Toxicologie du Quebec (CTQ) proficiency testing (PT) samples. The limit of detection (LOD) for iHg, MeHg, and EtHg in human blood was determined to be 0.27, 0.12, and 0.16 mug/L, respectively.