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.

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.

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.

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.

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).

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.

Urine strontium-90 (Sr-90) manual and automated pre-analytical separation followed by liquid scintillation counting.

Responding to a radiological or nuclear incident may require assessing tens to hundreds of thousands of people for possible radionuclide contamination. The measurement of radioactive Sr is important because of its impact on people's health. The existing analytical method for urine Sr-90 analysis using crown ethers is laborious and involves possible exposure to concentrated acids; therefore, this work is devoted to the development of the automated Sr-90 separation process, which became possible with the prepFast pre-analytical system (Elemental Scientific, Inc).

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.

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.

Development and validation of a biomonitoring method to measure As, Cr, and Ni in human urine samples by ICP-UCT-MS.

We developed an inductively coupled plasma mass spectrometry (ICP-MS) method using Universal Cell Technology (UCT) with a PerkinElmer NexION ICP-MS, to measure arsenic (As), chromium (Cr), and nickel (Ni) in human urine samples. The advancements of the UCT allowed us to expand the calibration range to make the method applicable for both low concentrations of biomonitoring applications and high concentrations that may be observed from acute exposures and emergency response. Our method analyzes As and Ni in kinetic energy discrimination (KED) mode with helium (He) gas, and Cr in dynamic reaction cell (DRC) mode with ammonia (NH3) gas. The combination of these elements is challenging because a carbon source, ethanol (EtOH), is required for normalization of As ionization in urine samples, which creates a spectral overlap (40Ar12C+) on 52Cr. This method additionally improved lab efficiency by combining elements from two of our previously published methods(Jarrett et al., 2007; Quarles et al., 2014) allowing us to measure Cr and Ni concentrations in urine samples collected as part of the National Health and Nutrition Examination Survey (NHANES) beginning with the 2017-2018 survey cycle. We present our rigorous validation of the method selectivity and accuracy using National Institute of Standards and Technology (NIST) Standard Reference Materials (SRM), precision using in-house prepared quality control materials, and a discussion of the use of a modified UCT, a BioUCell, to address an ion transmission phenomenon we observed on the NexION 300 platform when using higher elemental concentrations and high cell gas pressures. The rugged method detection limits, calculated from measurements in more than 60 runs, for As, Cr, and Ni are 0.23 µg L-1, 0.19 µg L-1, and 0.31 µg L-1, respectively.

Importance of Preanalytical Factors in Measuring Cr and Co Levels in Human Whole Blood: Contamination Control, Proper Sample Collection and Long-Term Storage Stability.

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 the 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 as 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 that there was no Cr and Co leaching from the limited sets of stainless steel needles used in these studies. Furthermore, we demonstrated that Cr and Co human whole blood samples are stable for 1 year stored at temperatures of -70, -20 and 4°C and 6 months at room temperature.

Determination of 226Ra in Urine Using Triple Quadrupole Inductively Coupled Plasma Mass Spectrometry.

Measuring 226Ra in urine at low levels is critical for both biomonitoring and radiological emergency response. Here we report a new analytical method to quantify 226Ra, as developed and validated by a simple dilute-and-shoot procedure, followed by Inductively Coupled Plasma-triple quadrupole-mass spectrometry detection using 'No Gas MS-MS' mode. The method provides rapid and accurate results for 226Ra with a limit of detection (LOD) down to 0.007 ng/l (0.26 Bq/l). This LOD is well below the recommended action levels for 226Ra detection in children and pregnant women (C/P) set by the Clinical Decision Guide (NCRP Report #161). Results for 226Ra obtained by this method are within ±7.0% of the target values of standard reference materials spiked in the urine.

Determination of 237Np and 239Pu in Urine Using Sector Field Inductively Coupled Plasma Mass Spectrometry (SF-ICP-MS).

Measuring 237Np and 239Pu in urine at low levels is important for both biomonitoring and radiological emergency response. Here we report a newly developed and validated analytical method used to determine 237Np and 239Pu in urine by selective retention of Np and Pu from 2mL of urine directly onto TEVA® resin followed by SF-ICP-MS (coupled to a membrane desolvating introduction system) detection. The method provides solid phase extraction of Np/Pu with observed recovery ratios ranging from 89% to 113% and rapid results with limits of detection well below recommended detection guidelines for children and pregnant women (NCRP 161 reference).

The effect of quench agent on urine bioassay for various radionuclides using Quantulus™1220 and Tri-Carb™3110.

Following a radiological or nuclear incident, the National Response Plan has given the Department of Health and Human Services / Centers for Disease Control and Prevention the responsibility for assessing population's contamination with radionuclides. In the public health response to the incident, valuable information could be obtained in a timely and accurate manner by using liquid scintillation counting techniques to determine who has been contaminated above background for alpha and beta emitting radionuclides. The calibration plays a major role in this process therefore, knowing the effect of quench agents on calibration is essential.

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.

US CENTERS FOR DISEASE CONTROL AND PREVENTION EXPERIENCE IN THE JOINT EXTERNAL EVALUATION PROCESS-RADIATION EMERGENCIES TECHNICAL AREA.

In 2015-16, the US Department of Health and Human Services led 23 US Government (USG) agencies including the Centers for Disease Control and Prevention (CDC), and more than 120 subject matter experts in conducting an in-depth review of the US core public health capacities and evaluation of the country's compliance with the International Health Regulations using the Joint External Evaluation (JEE) methodology. This two-part process began with a detailed 'self-assessment' followed by a comprehensive independent, external evaluation conducted by 15 foreign assessors. In the Radiation Emergencies Technical Area, on a scale from 1-lowest to 5-highest, the assessors concurred with the USG self-assessed score of 3 in both of the relevant indicators. The report identified five priority actions recommended to improve the USG capacity to handle large-scale radiation emergencies. CDC is working to implement a post-JEE roadmap to address these priority actions in partnership with national and international partners.