High-Throughput Determination of Ultratrace Actinides in Urine by In-Line Extraction Chromatography Combined with Quadrupole Inductively Coupled Plasma Mass Spectrometry (EC-ICP-MS).

Determining actinides in urine is vital for occupational exposure monitoring and radiological emergency response because of the toxicity and radiological dose effects of actinides on human health. Traditional radiochemistry analytical methods used to determine actinide concentrations in urine are time-consuming (sample analysis takes several days) and are hindered by a variety of technical and instrumentation-related obstacles. A high-throughput, fully automated, precise, and accurate in-line method was developed for determining five actinides (241Am, 239Pu, 237Np, 232Th, and 238U) at ng/L levels in urine using extraction chromatography combined with quadrupole inductively coupled plasma mass spectrometry (EC-ICP-MS). In this method, the five actinides were successfully separated with the required sensitivity, peak shape, and resolution using a simplified single Eichrom TRU column with a Dionex ICS-5000 system. The separated actinides were subsequently injected into an in-line PerkinElmer (PE) NexION 300D ICP-MS for quantitative determination. The sample-to-sample run time was 23 min for automatic chemical separation and quantification using only 0.5 mL of urine. The limits of detection (LOD) obtained using this method were 0.015, 0.022, 0.039, 4.5, and 2.4 ng/L for 241Am, 239Pu, 237Np, 232Th, and 238U, respectively. The method routinely had a chemical yield of >84% as well as a linearity (R2) coefficient of ≥0.999 for the calibrators. The method proved to be rapid, reliable, and effective for actinide quantification in urine and therefore is appropriate for radiological emergency response incidents.

Update of the Blood Lead Reference Value - United States, 2021.

The negative impact of lead exposure on young children and those who become pregnant is well documented but is not well known by those at highest risk from this hazard. Scientific evidence suggests that there is no known safe blood lead level (BLL), because even small amounts of lead can be harmful to a child's developing brain (1). In 2012, CDC introduced the population-based blood lead reference value (BLRV) to identify children exposed to more lead than most other children in the United States. The BLRV should be used as a guide to 1) help determine whether medical or environmental follow-up actions should be initiated for an individual child and 2) prioritize communities with the most need for primary prevention of exposure and evaluate the effectiveness of prevention efforts. The BLRV is based on the 97.5th percentile of the blood lead distribution in U.S. children aged 1-5 years from National Health and Nutrition Examination Survey (NHANES) data. NHANES is a complex, multistage survey designed to provide a nationally representative assessment of health and nutritional status of the noninstitutionalized civilian adult and child populations in the United States (2). The initial BLRV of 5 µg/dL, established in 2012, was based on data from the 2007-2008 and 2009-2010 NHANES cycles. Consistent with recommendations from a former advisory committee, this report updates CDC's BLRV in children to 3.5 µg/dL using NHANES data derived from the 2015-2016 and 2017-2018 cycles and provides helpful information to support adoption by state and local health departments, health care providers (HCPs), clinical laboratories, and others and serves as an opportunity to advance health equity and environmental justice related to preventable lead exposure. CDC recommends that public health and clinical professionals focus screening efforts on populations at high risk based on age of housing and sociodemographic risk factors. Public health and clinical professionals should collaborate to develop screening plans responsive to local conditions using local data. In the absence of such plans, universal BLL testing is recommended. In addition, jurisdictions should follow the Centers for Medicare & Medicaid Services requirement that all Medicaid-enrolled children be tested at ages 12 and 24 months or at age 24-72 months if they have not previously been screened (3).

Very low-level prenatal mercury exposure and behaviors in children: the HOME Study.

BACKGROUND: Mercury is toxic to the developing brain, but the lowest concentration associated with the development of behavior problems is unclear. The purpose of this study was to examine the association between very low-level mercury exposure during fetal development and behavior problems in children. METHODS: We used data from 389 mothers and children in a prospective pregnancy and birth cohort study. We defined mean prenatal mercury concentration as the mean of total whole blood mercury concentrations in maternal samples collected at 16- and 26-weeks of gestation, delivery, and neonatal cord blood samples. We assessed parent-reported child behavior up to five times from two to 8 years of age using the Behavioral Assessment System for Children (BASC-2). At 8 years of age, we assessed self-reported child anxiety using the Spence Children's Anxiety Scale (SCAS). We used multiple linear mixed models and linear regression models to estimate the association between mean prenatal mercury concentrations and child behavior and anxiety, respectively. RESULTS: The median prenatal total blood mercury concentrations was 0.67 µg/L. Overall, we did not find statistically significant associations between mean prenatal mercury concentrations and behavior problems scores, but a 2-fold increase in mercury concentrations at 16-weeks gestation was associated with 0.83 point (95% CI: 0.05, 1.62) higher BASC-2 anxiety scores. Maternal and cord blood mercury concentrations at delivery were associated with parent-reported anxiety at 8 years. CONCLUSION: We found limited evidence of an association between very-low level prenatal mercury exposure and behaviors in children, with an exception of anxiety.

LAMP: A CDC Program to Ensure the Quality of Blood-Lead Laboratory Measurements.

CONTEXT: The Lead and Multielement Proficiency (LAMP) program is an external quality assurance program promoting high-quality blood-lead measurements. OBJECTIVES: To investigate the ability of US laboratories, participating in the Centers for Disease Control and Prevention (CDC) LAMP program to accurately measure blood-lead levels (BLL) 0.70 to 47.5 µg/dL using evaluation criteria of ±2 µg/dL or 10%, whichever is greater. METHODS: The CDC distributes bovine blood specimens to participating laboratories 4 times per year. We evaluated participant performance over 5 challenges on samples with BLL between 0.70 and 47.5 µg/dL. The CDC sent 15 pooled samples (3 samples shipped in 5 rounds) to US laboratories. The LAMP laboratories used 3 primary technologies to analyze lead in blood: inductively coupled plasma mass spectrometry, graphite furnace atomic absorption spectroscopy, and LeadCare technologies based on anodic stripping voltammetry. Laboratories reported their BLL analytical results to the CDC. The LAMP uses these results to provide performance feedback to the laboratories. SETTING: The CDC sent blood samples to approximately 50 US laboratories for lead analysis. PARTICIPANTS: Of the approximately 200 laboratories enrolled in LAMP, 38 to 46 US laboratories provided data used in this report (January 2017 to March 2018). RESULTS: Laboratory precision ranged from 0.26 µg/dL for inductively coupled plasma mass spectrometry to 1.50 µg/dL for LeadCare instruments. All participating US LAMP laboratories reported accurate BLL for 89% of challenge samples, using the ±2 µg/dL or 10% evaluation criteria. CONCLUSIONS: Laboratories participating in the CDC's LAMP program can accurately measure blood lead using the current Clinical Laboratory Improvement Amendments of 1988 guidance of ±4 µg/dL or ±10%, with a success rate of 96%. However, when we apply limits of ±2 µg/dL or ±10%, the success rate drops to 89%. When challenged with samples that have target values between 3 and 5 µg/dL, nearly 100% of reported results fall within ±4 µg/dL, while 5% of the results fall outside of the acceptability criteria used by the CDC's LAMP program. As public health focuses on lower blood lead levels, laboratories must evaluate their ability to successfully meet these analytical challenges surrounding successfully measuring blood lead. In addition proposed CLIA guidelines (±2 µg/dL or 10%) would be achievable performance by a majority of US laboratories participating in the LAMP program.

Determination of Iodine Content in Dairy Products by Inductively Coupled Plasma Mass Spectrometry.

A probing study to establish a reliable and robust method for determining the iodine concentration using the ELAN® DRC™ II ICP-MS was performed in combination with a sample digestion and filtration step. Dairy products from locally available sources were evaluated to help determine the possibility and need for further evaluations in relation to the U.S. population's iodine intake. Prior to analysis, the samples were aliquoted and digested for 3 hours at 90±3 °C. Dilution and filtration were performed, following the digestion. The sample extract was analyzed, and the results were confirmed with NIST SRM 1549a Whole Milk Powder. Further experimentation will need to be performed to optimize the method for projected sample concentration and throughput.

Trace Metals Screening Process of Devices Used for the Collection, Analysis, and Storage of Biological Specimens.

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 pre-analytical, analytical, and post-analytical 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.

Analytical method for total chromium and nickel in urine using an inductively coupled plasma-universal cell technology-mass spectrometer (ICP-UCT-MS) in kinetic energy discrimination (KED) mode.

Biomonitoring and emergency response measurements are an important aspect of the Division of Laboratory Sciences of the National Center for Environmental Health, Centers for Disease Control and Prevention (CDC). The continuing advancement in instrumentation allows for enhancements to existing analytical methods. Prior to this work, chromium and nickel were analyzed on a sector field inductively coupled plasma-mass spectrometer (SF-ICP-MS). This type of instrumentation provides the necessary sensitivity, selectivity, accuracy, and precision but due to the higher complexity of instrumentation and operation, it is not preferred for routine high throughput biomonitoring needs. Instead a quadrupole based method has been developed on a PerkinElmer NexION™ 300D ICP-MS. The instrument is operated using 6.0 mL min-1 helium as the collision cell gas and in kinetic energy discrimination mode, interferences are successfully removed for the analysis of 52Cr (40Ar12C and 35Cl16O1H) and 60Ni (44Ca16O). The limits of detection are 0.162 µg L-1 Cr and 0.248 µg L-1 Ni. Method accuracy using NIST SRM 2668 level 1 (1.08 µg L-1 Cr and 2.31µg L-1 Ni) and level 2 (27.7 µg L-1 Cr and 115 µg L-1 Ni) was within the 95% confidence intervals reported in the NIST certificate. Among-run precision is less than 10% RSDs (N = 20) for in house quality control and NIST SRM urine samples. While the limits of detection (LOD) for the new quadrupole ICP-UCT-MS with KED method are similar to the SF-ICP-MS method, better measurement precision is observed for the quadrupole method. The new method presented provides fast, accurate, and more precise results on a less complex and more robust ICP-MS platform.

Measurement of mercury species in human blood using triple spike isotope dilution with SPME-GC-ICP-DRC-MS.

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(®) 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 (NaBPr(4)) 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 Québec (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 µg/L, respectively.

Total and methyl mercury in whole blood measured for the first time in the U.S. population: NHANES 2011-2012.

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, 1.58 µg/L (95% CI 1.29, 1.93) and THg, 1.86 µg/L (1.58, 2.19), followed by non-Hispanic blacks with MeHg, 0.52 µg/L (0.39, 0.68) and THg, 0.68 µg/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 >5.8 µg/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 >5.8 µg/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 integration of high-throughput testing of blood donors for cardiovascular disease risk assessment and prevention.

BACKGROUND AND OBJECTIVES: Some blood centers provide health screening as a public health measure and to encourage donation. The goal of the current study was to provide cardiovascular disease (CVD) screening to donors using high-throughput testing and web-based communications. MATERIALS AND METHODS: CVD risk screening was offered to donors at selected mobile drives in a large metropolitan area. Risk factors were determined by donor questionnaire, laboratory testing (total cholesterol, HDL levels and hemoglobin A1c), and blood pressure measurement. Results were reported to participants via mail and website. A 60-day follow up web-based survey was sent to participants via email to assess the impact of the program on donor's behavior. RESULTS: 9435 donors, 17-75 years old participated with the following risk factors: 61.3% BMIs>25, 28.8% high total cholesterol, and 31.4% lower than recommended HDL levels. 25.3% of donors that responded to the follow up survey went to see their health care provider based on screening results and 9% of these received new or modified treatment. CONCLUSION: In our sample, blood donors are healthier than the general population, but many still have CVD risk factors, particularly obesity. CVD screening can be successfully used to make donors aware of this important health information and some donors act on this information.

Rapid determination of thorium in urine by quadrupole inductively coupled plasma mass spectrometry (Q-ICP-MS).

Inductively coupled plasma mass spectrometry (ICP-MS) has proven to be an excellent analytical technique with high sensitivity for detecting low levels of long-lived radionuclides, such as thorium. However, the high-sensitivity technique increases the memory effect of thorium. This study developed a rapid, high-throughput, simple method for measuring thorium in urine using quadrupole inductively coupled plasma mass spectrometry (Q-ICP-MS). Replacing the commonly used hazardous hydrofluoric acid with a rinse solution of 0.025 mol/L oxalic acid and 5% (v/v) nitric acid eliminated the memory effect of thorium. 233U was used as internal standard in this study. The limit of detection (LOD) for thorium in this study is 0.77 ng/L, which is comparable to those of reported methods using more sophisticated and expensive sector field inductively coupled plasma mass spectrometry (SF-ICP-MS). This proposed method can determine thorium concentrations in urine in both occupationally exposed workers and populations that live in areas with high background levels of thorium.

Lead poisoning among asymptomatic individuals with a long-term history of opiate use in Golestan Cohort Study.

BACKGROUND: Recent reports of lead poisoning suggest that people who use opium may be exposed to high amounts of lead. Here, we investigate the association between opium use and blood lead levels (BLL) in a population-based cohort study. METHODS: In 2017, we studied a random sample of 410 people who currently (both within the past year and the past month) used opium and 104 who did not from participants of the Golestan Cohort Study in northeast Iran. Participants were stratified by sex and tobacco use history, completed a comprehensive opiate and tobacco use questionnaire and provided blood. BLL was measured by Lead Care® II Blood Lead Test Kit, validated by inductively coupled plasma triple quadrupole mass spectrometry. BLL was categorized as "<5 µg/dL", "elevated" (5-10 µg/dL), "high" (10-50 µg/dL), and "very high" (above 50 µg/dL). To assess the association between BLL categories and opiate use, route of consumption and weekly use, we used ordered logistic regression models, and report OR (odds ratio) and 95% CI (confidence interval) adjusted for age, sex, place of residence, education, occupation, household fuel type, and tobacco use. RESULTS: In the cohort, participants used only raw (teriak) or refined (shireh) opium, which were smoked (45%, n = 184), taken orally (46%, n = 189), or both (9%, n = 37), for a mean duration of 24.2 (standard deviation: 11.6) years. The median BLL was significantly higher in people who currently used opium (11.4 µg/dL; IQR: 5.2-23.4) compared with those who did not (2.3 µg/dL; IQR: 2.3-4.2), and the highest median BLL was seen in oral use (21.7 µg/dL; IQR: 12.1-34.1). The BLL was <5 µg/dL among 79.8% of people with no opiate use, compared with only 22.7% in those using opium. BLL was elevated in 21.7%, high in 50.5% and very high in 5.1% of people using opium. About 95% of those with oral (180/189) or dual use (35/37) and 55% (102/184) of those who smoked opium had levels of blood lead above 5 µg/dL. The OR for the association between any opium use and each unit of increase in BLL category was 10.5 (95%CI: 5.8-19.1), and oral use of opium was a very strong predictor of increasing BLL category (OR=74.1; 95%CI: 35.1-156.3). This odds ratio was 38.8 (95%CI: 15.9-95.1) for dual use and 4.9 (95%CI: 2.6-9.1) for opium smoking. There was an independent dose-response association between average weekly dose and BLL among people using opium, overall and when stratified by route of use. CONCLUSION: Our results indicate that regular use of lead-adulterated opium can expose individuals to high levels of lead, which may contribute to mortality and cancer risks associated with long-term opium use.

Efficacy of succimer chelation of mercury at background exposures in toddlers: a randomized trial.

OBJECTIVE: To examine whether succimer, a mercaptan compound known to reduce blood lead concentration in children, reduces blood mercury concentration. STUDY DESIGN: We used samples from a randomized clinical trial of succimer chelation for lead-exposed children. We measured mercury levels in pre-treatment samples from 767 children. We also measured mercury levels in blood samples drawn 1 week after treatment began (n = 768) and in a 20% random sample of the children who received the maximum 3 courses of treatment (n = 67). A bootstrap-based isotonic regression method was used to compare the trend with time in the difference between the adjusted mean mercury concentrations in the succimer group and that in the placebo group. RESULTS: The adjusted mean organic mercury concentration in the succimer group relative to the placebo group fell from 99% at baseline to 82% after 3 courses of treatment (P for trend = .048), but this resulted from the prevention of the age-related increase in the succimer group. CONCLUSION: Succimer chelation for low level organic mercury exposure in children has limited efficacy.

Limit of detection comparison on urine gross alpha/beta, H-3, and P-32 analysis between different liquid scintillation counters.

As part of the Centers for Disease Control and Prevention's post-radiological/nuclear incident response mission, we developed rapid bioassay analytical methods to assess possible human exposure to radionuclides and internal contamination. Liquid scintillation counting (LSC) is a valuable analytical tool for the rapid detection and quantification of gross alpha/beta-emitting radionuclides in urine samples. A key characteristic of this type of bioassay method is its detection sensitivity for the priority threat radionuclides. We evaluated the limit of detection of selected LSC instruments to determine which instrument can be used when low-dose measurement is important.

Rapid HPGe well detector gamma bioassay of 137Cs, 60Co, and 192Ir method.

CDC designed a rapid HPGe Bioassay Method for 137Cs, 60Co, and 192Ir that is suitable for a public health response to a radiological incident where people may ingest or inhale radionuclides. The method uses a short count time, small sample volume, and a large volume detector and well size. It measures a patient's urine sample collected post-incident. The levels of concern are directly related to the Clinical Decision Guide levels recommended in the National Council of Radiation Protection 161.

Determination of Pu-239 in Urine by Sector Field Inductively Coupled Plasma Mass Spectrometry (SF-ICP-MS) Using an Automated Offline Sample Preparation Technique.

Here we report a new procedure to determine Pu-239 in urine using a custom-made automated pre-analytical processing system (single probe) with Pu-242 as a tracer followed by analysis by SF-ICP-MS. An average Pu-242 recovery rate of 88% was obtained with CF-ThU-1000 columns reused >100 times. Analytical results agree with measurements obtained using the CDC manual method with a R2 of 0.9994. Results for Oak Ridge National Laboratory (ORNL) reference materials (RM) align with target values with a bias range of -3.44% to 3.05%. The limit of detection for this method is 0.63 pg/L, which is comparable to previous manual methods.

Universal use of alpha/beta mode in liquid scintillation counting analysis for both alpha/beta and single nuclide determination.

Nuclear industry advancements and growing concerns about environmental contamination and terrorist activity have increased interest in quantifying radioisotopes in environmental and human samples. Increased presence in the environment, ease of entry into the food chain, nuclear medicine applications, and the possibility of radiological terrorism incidents can lead to human intake of these radionuclides [1,2]. A universal method to screen for and quantify individual radionuclides as well as both levels of alpha and beta emitters would address these concerns.

The effect of Sr resin cartridge age on stable Sr recovery methods used in Sr-90 analysis.

Radioactive strontium is a nuclear fission decay product found in industrial products and nuclear waste and is released during nuclear accidents. Current urine radiostrontium separation methods often are based on the use of Sr resin columns or cartridges (Eichrom Technologies). Most of these analytical methods use stable Sr as a tracer, with subsequent Sr recovery. The gravimetric recovery method requires 120 times more stable Sr than does the inductively coupled plasma mass spectrometry method described here. This difference can affect cartridge performance especially with aging cartridges.

Urine gross alpha/beta bioassay method development using liquid scintillation counting techniques.

In the case of a radiological or nuclear incident, valuable information could be obtained in a timely manner by using Liquid Scintillation Counting (LSC) technique through fast screening of urine samples from potentially contaminated persons. This work describes the optimization of LSC parameters on PerkinElmer (PE) Tri-Carb and Quantulus GCT series instruments to develop a rapid method for screening urine in an emergency response situation.