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Background As part of Government of Canada’s Chemical Management Plan, substances containing aluminum (Al), bismuth (Bi), cerium (Ce), chromium (Cr), germanium (Ge), lanthanum (La), lithium (Li), neodymium (Nd), praseodymium (Pr), tellurium (Te), titanium (Ti) and yttrium (Y) were identified as priorities for risk assessment. Generating exposure estimates from all routes of exposure from multiple sources using a traditional approach for these elements can be challenging. The use of human biomonitoring (HBM) data would allow for direct and more precise assessment of the internal concentrations from all routes and all sources of exposure. There are no Canadian or North American population-level whole blood HBM data for the elements listed above. Therefore, this is the first biomonitoring project carried out to determine the concentrations of these elements from a nationally representative sample of Canadians. Objectives The objective of this study was to generate whole blood concentrations for Al, Bi, Ce, Cr, Ge, La, Li. Nd, Pr, Te, Ti and Y in the Canadian population using biobank samples from the Canadian Health Measures Survey (CHMS) cycle 2 (2009–2011) for use in characterizing exposure in screening assessments and for establishing baseline concentrations to determine how exposures are changing over time. Methods The sample analysis was conducted by ICP-MS. A rigorous quality control and quality assurance process was implemented in order to generate data with high accuracy and precision while measuring low concentrations and minimizing possible inadvertent contamination. Results Of the elements analysed, the whole blood concentrations (μg/L) of Al, Ce, Cr, Ge, La, Nd, Pr, Te, Ti and Y in the Canadian population aged 3–79 years were below their respective method reporting limit (MRL). Two elements, Bi and Li were detected in 5 % and 66 % of the Canadian population. The median Li concentration was 0.47 μg/L. Conclusion The results of this study provide information on concentrations of these elements in the Canadian population which can be utilized to characterize exposure in screening assessments and there by the potential for harm to human health. In addition, this study provides baseline HBM data which can be used as a comparative HBM dataset for other populations with similar exposure patterns.

Population-level biomonitoring of tin in urine has been conducted by the U.S. National Health and Nutrition Examination Survey (NHANES) and the National Nutrition and Health Study (ENNS – Étude nationale nutrition santé) in France. The general population is predominantly exposed to inorganic tin from the consumption of canned food and beverages. The National Institute for Public Health and the Environment of the Netherlands (RIVM) has established a tolerable daily intake (TDI) for chronic exposure to inorganic tin based on a NOAEL of 20 mg/kg bw per day from a 2-year feeding study in rats. Using a urinary excretion fraction (0.25%) from a controlled human study along with a TDI value of 0.2 mg/kg bw per day, a Biomonitoring Equivalent (BE) was derived for urinary tin (26 μg/g creatinine or 20 μg/L urine). The geometric mean and the 95th percentile tin urine concentrations of the general population in U.S. (0.705 and 4.5 μg/g creatinine) and France (0.51 and 2.28 μg/g creatinine) are below the BE associated with the TDI, indicating that the population exposure to inorganic tin is below the exposure guidance value of 0.2 mg/kg bw per day. Overall, the robustness of pharmacokinetic data forming the basis of the urinary BE development is medium. The availability of internal dose and kinetic data in the animal species forming the basis of the assessment could improve the overall confidence in the present assessment.

Background Few studies of maternal prenatal fish intake have included biomarkers of exposure to mercury, long-chain n-3 fatty acids, and selenium, which are hypothesized to mediate associations with child neurodevelopment. Objectives Examine associations of maternal prenatal fish intake with child neurodevelopment accounting for biomarkers. Methods In 1999–2002 we enrolled pregnant women into the Project Viva cohort. At median 27.9 weeks gestation, we estimated maternal fish intake using food frequency questionnaires, and collected blood. We assayed erythrocytes for total mercury and selenium, and plasma for fatty acids including n-3 docosahexaenoic acid (DHA) and eicosapentaenoic acid (EPA). In mid-childhood (median 7.7 years), we administered cognitive tests including the Kauffman Brief Intelligence Test (KBIT). We performed multivariable linear regression analyses adjusting for maternal and child characteristics including home environment and maternal intelligence. Results Among 1068 pairs (872 with blood), mean (SD) exposures were: maternal fish intake 1.7 (1.5) servings/week, mercury 4.0 (3.6) ng/g, DHA + EPA 98.4 (41.8) mcg/ml, selenium 205.6 (34.6) ng/ml. Child KBIT verbal scores (mean 112.2, SD 15.0) were not related to any exposures: maternal fish intake (0.15; 95% CI: − 0.50, 0.79), mercury (0.08; − 0.18, 0.35), DHA + EPA (0.01; − 0.22, 0.24), and selenium (0.20; − 0.09, 0.50). Associations with KBIT nonverbal scores and tests of memory and visual motor abilities were similarly null. Mutual adjustment for each of the exposure measures did not substantially change estimates. Conclusions In this population with an average fish consumption of about 1 1/2 weekly servings, we did not see any evidence for an association of maternal prenatal fish intake, or of mercury, DHA + EPA, or selenium status, with verbal or non-verbal intelligence, visual motor function, or visual memory at median 7.7 years of age.

Background: The use of human biomonitoring data allows direct and more precise assessment of the distribution of exposure in a given population. In Canada, biomonitoring data in the general populat...

This study investigated three area sampling approaches for using metal impurities in carbon nanotubes (CNTs) to identify CNT releases in workplace environments: air concentrations (μg/m3), surface loadings (μg/cm2), and passive deposition rates (μg/m2/h). Correlations between metal impurities and CNTs were evaluated by collecting simultaneous colocated area samples for thermal-optical analysis (for CNTs) and ICP-MS analysis (for metals) in a CNT manufacturing facility. CNTs correlated strongly with Co (residual catalyst) and Ni (impurity) in floor surface loadings, and with Co in passive deposition samples. Interpretation of elemental ratios (Co/Fe) assisted in distinguishing among CNT and non-CNT sources of contamination. Stable isotopes of Pb impurities were useful for identifying aerosolized CNTs in the workplace environment of a downstream user, as CNTs from different manufacturers each had distinctive Pb isotope signatures. Pb isotopes were not useful for identifying CNT releases within a CNT manufacturing environment, however, because the CNT signature reflected the indoor background signature. CNT manufacturing companies and downstream users of CNTs will benefit from the availability of alternative and complementary strategies for identifying the presence/absence of CNTs in the workplace and for monitoring the effectiveness of control measures.

Childhood blood pressure (BP) is an important determinant of adult cardiovascular disease. Prenatal exposure to methylmercury through maternal fish consumption has been reported to increase the BP of children years later.Mother-child pairs were enrolled from Project Viva, a prospective cohort study in Massachusetts. From second trimester maternal blood samples, we measured erythrocyte mercury concentration. Systolic BP in children, measured up to 5 times per visit in early and mid-childhood (median ages 3.2 and 7.7 years), was the primary outcome. We used mixed-effect regression models to account for variation in the number of BP measurements and to average effects over both time points.Among 1103 mother-child pairs, mean (SD) second trimester total erythrocyte mercury concentration was 4.0 (3.9)ng/g among mothers whose children were assessed in early childhood and 4.0 (4.0)ng/g for children assessed in mid-childhood. Mean (SD) offspring systolic BP was 92.1 (10.4)mm Hg in early childhood and 94.3 (8.4)mm Hg in mid-childhood. After adjusting for mother and infant characteristics, mean second trimester blood mercury concentration was not associated with child systolic BP (regression coefficient, 0.1mm Hg; 95% CI, -1.3 to 1.5 for quartile 4 vs. quartile 1) at either time period. Further adjusting for second trimester maternal fish consumption, as well as docosahexaenoic acid and eicosapentaenoic acid consumption, did not substantially change the estimates.The results of this study demonstrate an absence of association between childhood blood pressure and low-level mercury exposure typical of the general US population.

Oral bioaccessibility estimates for six metals which are prevalent as contaminants in Canada (zinc, lead, cadmium, copper, nickel, and chromium) are investigated for house dust using the simple gastric phase versus the two-phase physiologically-based extraction technique (PBET). The purpose is to determine whether a complete gastrointestinal (GI) assay yields a more conservative (i.e., higher) estimate of metal bioaccessibility in house dust than the gastric phase alone (G-alone). The study samples include household vacuum dust collected from 33 homes in Montreal, Canada, plus four certified reference materials (NIST 2583, NIST 2584, NIST 2710 and NIST 2710a). Results indicate that percent bioaccessibilities obtained using G-alone are generally greater than or equivalent to those obtained using the complete GI simulation for the six studied metals in house dust. Median bioaccessibilities for G-alone/GI in household vacuum dust samples (n = 33) are 76.9%/19.5% for zinc, 50.4%/6.2% for lead, 70.0%/22.4% for cadmium, 33.9%/30.5% for copper and 28.5%/20.7% for nickel. Bioaccessible chromium is above the detection limit in only four out of 33 samples, for which G-alone results are not significantly different from GI results (p = 0.39). It is concluded that, for the six studied metals, a simple G-alone extraction provides a conservative and cost-effective approach for estimating oral bioaccessibility of metals in house dust.

Ayurveda is a traditional form of medicine used by majority of the Indians. Here we report three cases of lead toxicity, following intake of Ayurvedic medicines. Three patients presented with blood lead levels (BLLs) of 122.4, 115 and 42.8 μg/dl respectively at the time of hospitalization. The first case was chelated with D- penicillamine, the second with calcium disodium ethylene diamino tetra acetate (EDTA) and the third with environmental intervention and education. Associated Ayurvedic products were collected from patients and analyzed for metallic concentration. Cessation of Ayurvedic medication along with chelation, nutritional intervention and education, reduced the BLL to 27.4 μg/dl in the first case after 1 year, 21.1 μg/dl after 9 months in the second and 18.2 μg/dl after 6 months in the third case.

Chronic kidney disease of unknown etiology (CKDu) has emerged as a significant public health problem in Sri Lanka. The role of environmental exposure to cadmium and arsenic in the aetiology of CKDu is still unclear. Identification of a panel of novel urinary biomarkers would be invaluable in the study of toxin mediated damage postulated to be the aetiology of CKDu.The aims of this study were to evaluate the profile of novel urinary biomarkers in CKDu patients and identify any association with environmental exposure to heavy metals.Thirty seven randomly selected CKDu patients attending a renal clinic in the North Central Province and two control groups namely a farmer group (n=39) and a non-farmer group (n=40) from a non-endemic area were included in this comparative cross sectional study. Urine samples were analyzed for heavy metals and five urinary biomarkers.CKDu patients had significantly elevated urinary levels of fibrinogen (198.2 ng/mg creatinine p0.001), clusterin (3479 ng/mg creatinine p0.001), cystatin-C (5124.8 ng/mg creatinine p0.001) and β2-microglobulin (9913.4 ng/mg creatinine p0.001) compared to the control groups. Fibrinogen and β2-microglobulin were the best to discriminate CKDu patients from normal individuals with the receiver operator areas under the curve being 0.867 and 0.853, respectively. Urinary fibrinogen and KIM-1 levels correlated positively with urinary arsenic levels. KIM-1 levels correlated positively with urinary mercury and lead levels but no correlation was seen with urinary cadmium levels.Fibrinogen and β2-microglobulin have the potential of being a screening tool for detection of CKDu and may aid the early diagnosis of toxin mediated tubular injury in CKDu. Their usefulness need to be further validated in a larger epidemiological study of patients with early stages of CKDu.

Maternal lead exposure is associated with poor birth outcomes in populations with moderate to high blood levels. However, no studies have looked at exposure levels commonly experienced by US women.We evaluated the relationship between maternal red blood cell (RBC) lead levels in midpregnancy and birth outcomes in 949 mother-child pairs in a prebirth cohort. We used multiple linear regression and logistic regression, adjusted for potential confounders including maternal age, race, prepregnancy body mass index, and smoking to relate maternal lead to infant birth size and risk for preterm birth (37 weeks).Mean RBC lead level was 1.2 μg/dL (range, 0.0-5.0). Mean (standard deviation) birthweight was 3505 (520) g, birthweight for gestational age z-score 0.22 (0.93), and length of gestation 39.5 (1.7) weeks. Mothers in the highest versus lowest lead quartile did not have higher odds (OR, 1.85; 95% confidence interval [CI], 0.79-4.34) of preterm delivery; after stratifying by child sex, there was an association among males (OR, 5.51; 95% CI, 1.21-25.15) but not females (OR, 0.82; 95% CI, 0.24-2.85). Maternal RBC lead was not associated with any continuous outcomes in combined or sex-stratified analyses.Maternal lead exposure, even at very low levels, may adversely affect some childbirth outcomes, particularly preterm birth among males.

Nanoscale drug delivery vehicles have been harnessed extensively as carriers for cancer chemotherapeutics. However, traditional pharmaceutical approaches for nanoformulation have been a challenge with molecules that exhibit incompatible physicochemical properties, such as platinum-based chemotherapeutics. Here we propose a paradigm based on rational design of active molecules that facilitate supramolecular assembly in the nanoscale dimension. Using cisplatin as a template, we describe the synthesis of a unique platinum (II) tethered to a cholesterol backbone via a unique monocarboxylato and O→Pt coordination environment that facilitates nanoparticle assembly with a fixed ratio of phosphatidylcholine and 1,2-distearoyl- sn -glycero-3-phosphoethanolamine- N -[amino (polyethylene glycol)-2000]. The nanoparticles formed exhibit lower IC 50 values compared with carboplatin or cisplatin in vitro, and are active in cisplatin-resistant conditions. Additionally, the nanoparticles exhibit significantly enhanced in vivo antitumor efficacy in murine 4T1 breast cancer and in K-Ras LSL/+ /Pten fl/fl ovarian cancer models with decreased systemic- and nephro-toxicity. Our results indicate that integrating rational drug design and supramolecular nanochemistry can emerge as a powerful strategy for drug development. Furthermore, given that platinum-based chemotherapeutics form the frontline therapy for a broad range of cancers, the increased efficacy and toxicity profile indicate the constructed nanostructure could translate into a next-generation platinum-based agent in the clinics.

Background Given mounting evidence for adverse effects from excess manganese exposure, it is critical to understand host factors, such as genetics, that affect manganese metabolism. Methods Archived blood samples, collected from 332 Mexican women at delivery, were analyzed for manganese. We evaluated associations of manganese with functional variants in three candidate iron metabolism genes: HFE [hemochromatosis], TF [transferrin], and ALAD [δ-aminolevulinic acid dehydratase]. We used a knockout mouse model to parallel our significant results as a novel method of validating the observed associations between genotype and blood manganese in our epidemiologic data. Results Percentage of participants carrying at least one copy of HFE C282Y, HFE H63D, TF P570S, and ALAD K59N variant alleles was 2.4%, 17.7%, 20.1%, and 6.4%, respectively. Percentage carrying at least one copy of either C282Y or H63D allele in HFE gene was 19.6%. Geometric mean (geometric standard deviation) manganese concentrations were 17.0 (1.5) μg/l. Women with any HFE variant allele had 12% lower blood manganese concentrations than women with no variant alleles (β = -0.12 [95% CI = -0.23 to -0.01]). TF and ALAD variants were not significant predictors of blood manganese. In animal models, Hfe-/- mice displayed a significant reduction in blood manganese compared with Hfe+/+ mice, replicating the altered manganese metabolism found in our human research. Conclusions Our study suggests that genetic variants in iron metabolism genes may contribute to variability in manganese exposure by affecting manganese absorption, distribution, or excretion. Genetic background may be critical to consider in studies that rely on environmental manganese measurements.

The high incidence of acute and chronic kidney injury due to various environmental factors such as heavy metals or chemicals has been a major problem in developing countries. However, the diagnosis of kidney injury in these areas can be more challenging due to the lack of highly sensitive and specific techniques that can be applied in point-of-care settings. To address this, we have developed a technique called ‘micro-urine nanoparticle detection (μUNPD)’, that allows the detection of trace amounts of molecular markers in urine. Specifically, this technique utilizes an automated on-chip assay followed by detection with a hand-held device for the read-out. Using the μUNPD technology, the kidney injury markers KIM-1 and Cystatin C were detected down to concentrations of 0.1 ng/ml and 20 ng/ml respectively, which meets the cut-off range required to identify patients with acute or chronic kidney injury. Thus, we show that the μUNPD technology enables point of care and non-invasive detection of kidney injury, and has potential for applications in diagnosing kidney injury with high sensitivity in resource-limited settings.

This study investigated the use of metal impurities in single-wall carbon nanotubes (SWCNT) as potential tracers to distinguish engineered nanomaterials from background aerosols. TEM and SEM were used to characterize parent material and aerosolized agglomerates collected on PTFE filters using a cascade impactor. SEM image analysis indicated that the SWCNT agglomerates contained about 45% amorphous carbon and backscatter electron analysis indicated that metal impurities were concentrated within the amorphous carbon component. Two elements present as impurities (Y and Ni) were selected as appropriate tracers in this case as their concentrations were found to be highly elevated in the SWCNT parent material (% range) compared to ambient air particles (μg/g range), and background air concentrations were below detection limits for both elements. Bioaccessibility was also determined using physiologically-based extractions at pH conditions relevant to both ingestion and inhalation pathways. A portable wet electrostatic precipitation system effectively captured airborne Y and Ni released during sieving processes, in proportions similar to the bulk sample. These observations support the potential for catalysts and other metal impurities in carbon nanotubes to serve as tracers that uniquely identify emissions at source, after an initial analysis to select appropriate tracers.

Measurement of lead in breast milk is an important public health consideration and can be technically quite challenging. The reliable and accurate determination of trace lead in human breast milk is difficult for several reasons including: potential for contamination during sample collection, storage, and analysis; complexities related to the high fat content of human milk; and poor analytic sensitivity at low concentrations. Breast milk lead levels from previous published studies should therefore be reviewed with caution. Due to the difficulty in identifying a method that would successfully digest samples with 100% efficiency, we evaluated three different digestion procedures including: (1) dry ashing in a muffle furnace, (2) microwave oven digestion, and (3) digestion in high pressure asher. High temperature, high pressure asher digestion was selected as the procedure of choice for the breast milk samples. Trace lead analysis was performed using isotope dilution (ID) inductively coupled plasma mass spectrometry (ICP-MS). Measured lead concentrations in breast milk samples (n = 200) from Mexico ranged from 0.2 to 6.7 ng ml−1. The precision for these measurements ranged from 0.27–7.8% RSD. Use of strict contamination control techniques and of a very powerful digestion procedure, along with an ID-ICP-MS method for lead determination, enables us to measure trace lead levels as low as 0.2 ng ml−1 in milk (instrument detection limit = 0.01 ng ml−1).