Derivation of biomonitoring equivalents (BE values) for zinc.

Zinc is an essential nutrient in which deficiency or excess exposure can result in adverse health effects. Several organizations have established exposure guidance values to protect against deficiency and toxicity. Population-level biomonitoring data for zinc in whole blood, serum and urine are available from the Canadian Health Measures Survey (CHMS) and the US National Health and Nutrition Examination Survey (NHANES). This paper derived Biomonitoring Equivalent values (BEs) for zinc. BEs are tools based upon exposure guidance values to interpret biomonitoring data in the context of potential health risks. A regression between intake and serum/plasma concentration was derived to generate BEs for serum/plasma and whole blood. BEs for urine were derived using mass balance approach with a urine excretion fraction of 0.04. The BE values for deficiency ranged from 860 to 866, 6017-6059 and 159-206 µg/L for serum/plasma, whole blood and urine, respectively. BEs to protect against toxicity for serum/plasma, whole blood, and urine were in the range of 895-1281, 6265-8969 and 439-3489 µg/L, respectively. When interpreting biomonitoring data in a health-risk context, urinary zinc may be a more reliable biomarker of exposure than blood due to homeostasis in blood.

Biomonitoring Equivalents for interpretation of urinary iodine.

Iodine is an essential nutrient whose deficiency or excess exposure can cause adverse health effects. The primary sources of iodine exposure in the general population are iodized salt, dairy products, bread and sea food. Urinary iodine concentrations (UIC) have been measured by Canadian Health Measures Survey (CHMS) and US National Health and Nutrition Examination Survey (NHANES). The Institute of Medicine (IOM), the US Agency for Toxic Substances and Disease Registry (ATSDR) and World Health Organization (WHO) have established exposure guidance values for nutrition (IOM Estimated Average Requirement (EAR), Recommended Dietary Allowance (RDA), WHO Recommended Nutrient Intake (RNI)) and toxicity (IOM Tolerable Upper Intake Level (UL); ATSDR Minimal Risk Level (MRL), WHO International Programme on Chemical Safety (IPCS) Tolerable Daily Intake (TDI)). Using a urinary excretion fraction of 0.9, Biomonitoring Equivalents (BE) for the EAR, RDA, UL and MRL were derived for adults (60, 100, 730 and 450 µg/L, respectively) and children (50, 80, 580 and 360 µg/L, respectively). The population median UIC values from NHANES and CHMS for adults (140-181, 122-126 µg/L, respectively) and children (232, 189 µg/L, respectively) were above the criteria for assessing iodine nutrition, indicating that US and Canadian populations are likely to have adequate population iodine nutrition. The median UIC from NHANES and CHMS do not exceed BE values derived from exposure guidance values for toxicity.

Development of biomonitoring equivalents for barium in urine and plasma for interpreting human biomonitoring data.

The objectives of the present work were: (1) to assemble population-level biomonitoring data to identify the concentrations of urinary and plasma barium across the general population; and (2) to derive biomonitoring equivalents (BEs) for barium in urine and plasma in order to facilitate the interpretation of barium concentrations in the biological matrices. In population level biomonitoring studies, barium has been measured in urine in the U.S. (NHANES study), but no such data on plasma barium levels were identified. The BE values for plasma and urine were derived from U.S. EPA's reference dose (RfD) of 0.2 mg/kg bw/d, based on a lower confidence limit on the benchmark dose (BMDL05) of 63 mg/kg bw/d. The plasma BE (9 µg Ba/L) was derived by regression analysis of the near-steady-state plasma concentrations associated with the administered doses in animals exposed to barium chloride dihydrate in drinking water for 2-years in a NTP study. Using a human urinary excretion fraction of 0.023, a BE for urinary barium (0.19 mg/L or 0.25 mg/g creatinine) was derived for US EPA's RfD. The median and the 95th percentile barium urine concentrations of the general population in U.S. are below the BE determined in this study, indicating that the population exposure to inorganic barium is expected to be below the exposure guidance value of 0.2 mg/kg bw/d.

Derivation of biomonitoring equivalent for inorganic tin for interpreting population-level urinary biomonitoring data.

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.

Biomonitoring Equivalents for molybdenum.

Molybdenum is an essential trace element for mammalian, plant, and other animal systems. The Institute of Medicine (IOM) has established an Estimated Average Requirement (EAR) to assure sufficient molybdenum intakes for human populations; however excessive exposures can cause toxicity. As a result, several agencies have established exposure guidance values to protect against molybdenum toxicity, including a Reference Dose (RfD), Tolerable Daily Intake (TDI) and a Tolerable Upper Intake Level (UL). Biomonitoring for molybdenum in blood or urine in the general population is being conducted by the Canadian Health Measures Survey (CHMS) and the U.S. National Health and Nutrition Examination Survey (NHANES). Using pharmacokinetic data from controlled human dosing studies, Biomonitoring Equivalents (BEs) were calculated for molybdenum in plasma, whole blood, and urine associated with exposure guidance values set to protect against both nutritional deficits and toxicity. The BEEAR values in plasma, whole blood and urine are 0.5, 0.45 and 22 µg/L, respectively. The BEs associated with toxicity range from 0.9 to 31 µg/L in plasma, 0.8-28 µg/L in whole blood and 200-7500 µg/L in urine. These values can be used to interpret molybdenum biomonitoring data from a nutritional and toxicity perspective.

Biomonitoring Equivalents for selenium.

Selenium is an essential nutrient for human health with a narrow range between essentiality and toxicity. Selenium is incorporated into several proteins that perform important functions in the body. With insufficient selenium intake, the most notable effect is Keshan disease, an endemic cardiomyopathy in children. Conversely, excessive selenium intake can result in selenosis, manifested as brittle nails and hair and gastro-intestinal disorders. As such, guidance values have been established to protect against both insufficient and excessive selenium exposures. Dietary Reference Intakes (DRIs) have been established as standard reference values for nutritional adequacy in North America. To protect against selenosis resulting from exposure to excessive amounts of selenium, several government and non-governmental agencies have established a range of guidance values. Exposure to selenium is primarily through the diet, but monitoring selenium intake is difficult. Biomonitoring is a useful means of assessing and monitoring selenium status for both insufficient and excessive exposures. However, to be able to interpret selenium biomonitoring data, levels associated with both DRIs and toxicity guidance values are required. Biomonitoring Equivalents (BEs) were developed for selenium in whole blood, plasma and urine. The BEs associated with assuring adequate selenium intake (Estimated Average Requirements - EAR) are 100, 80 and 10µg/L in whole blood, plasma and urine, respectively. The BEs associated with protection against selenosis range from 400 to 480µg/L in whole blood, 180-230µg/L in plasma, and 90-110µg/L in urine. These BE values can be used by both regulatory agencies and public health officials to interpret selenium biomonitoring data in a health risk context.

Interpreting biomonitoring data: Introducing the international human biomonitoring (i-HBM) working group's health-based guidance value (HB2GV) dashboard.

Human biomonitoring (HBM) data measured in specific contexts or populations provide information for comparing population exposures. There are numerous health-based biomonitoring guidance values, but to locate these values, interested parties need to seek them out individually from publications, governmental reports, websites and other sources. Until now, there has been no central, international repository for this information. Thus, a tool is needed to help researchers, public health professionals, risk assessors, and regulatory decision makers to quickly locate relevant values on numerous environmental chemicals. A free, on-line repository for international health-based guidance values to facilitate the interpretation of HBM data is now available. The repository is referred to as the "Human Biomonitoring Health-Based Guidance Value (HB2GV) Dashboard". The Dashboard represents the efforts of the International Human Biomonitoring Working Group (i-HBM), affiliated with the International Society of Exposure Science. The i-HBM's mission is to promote the use of population-level HBM data to inform public health decision-making by developing harmonized resources to facilitate the interpretation of HBM data in a health-based context. This paper describes the methods used to compile the human biomonitoring health-based guidance values, how the values can be accessed and used, and caveats with using the Dashboard for interpreting HBM data. To our knowledge, the HB2GV Dashboard is the first open-access, curated database of HBM guidance values developed for use in interpreting HBM data. This new resource can assist global HBM data users such as risk assessors, risk managers and biomonitoring programs with a readily available compilation of guidance values.

Multi-elemental determination of metals, metalloids and rare earth element concentrations in whole blood from the Canadian Health Measures Survey, 2009-2011.

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.

Characterization of Airborne Particles Emitted During Application of Cosmetic Talc Products.

A pilot study was undertaken to characterize the concentration, duration and particle size distribution of the talc cloud that forms in the personal breathing zone (PBZ) during application of certain talc-containing cosmetics. Multiple direct-reading instruments were employed to simultaneously monitor PM4 concentrations (particulate matter with aerodynamic diameter < 4 µm; mg/m3) at different distances from each of three subjects while they applied talc products. Results indicated that the purpose and method of applying the talc product, combined with behavioral and physical differences amongst subjects, all strongly influenced airborne talc concentrations and the duration of the cloud. Air concentrations of talc in the PBZ averaged around 1.0 mg/m3, and the duration of exposure varied from less than one minute to more than ten minutes. The real-time monitors captured the occasional formation of secondary clouds, likely caused by resuspension of talc particles from skin or other surfaces. Measurements of aerosolized baby powder, face powder, and two adult body powders indicated that the median aerodynamic diameter of the talc cloud ranged from 1.7 to 2.0 µm. These direct-reading approaches were valuable for providing detailed characterization of short duration exposures to airborne talc particles, and will be useful to support future exposure assessments of talc and other powders in consumer products.

A review of human biomonitoring data used in regulatory risk assessment under Canada's Chemicals Management Program.

As a part of the Chemicals Management Plan launched in 2006, the Government of Canada is assessing and managing, where appropriate, the potential health and ecological risks associated with approximately 4300 substances under the Canadian Environmental Protection Act (1999). Since that time, nearly 3000 substances have been assessed, with human biomonitoring (HBM) data playing an increasingly important role for some substances. Case studies are presented, including both inorganic and organic substances (i.e., selenium, triclosan, phthalates), which highlight the impact and overall role HBM has had in regulatory decision making in Canada for these three substances as well as criteria used in the application of HBM data in human health risk assessment. An overview of its limitations in terms of how and when HBM data can be applied, when assessing human health in a regulatory setting, is discussed as well as the role HBM data can play in priority setting.

Brominated flame retardant concentrations in sera from the Canadian Health Measures Survey (CHMS) from 2007 to 2009.

Pooling of surplus serum from individual samples, collected between 2007 and 2009 during Cycle 1 of the Canadian Health Measures Survey (CHMS), was performed to develop a national baseline estimate of brominated flame retardants in Canadians. Serum samples were categorized by sex and distributed by five age groups ranging from 6 to 79years. Nearly 5000 (4583) serum samples were used to form 59 composite pools. Serum pools were created to ensure a high detection frequency of these analytes in serum because low volume samples had previously resulted in non-detectable concentrations. The analytes of interest in these serum pools included 23 polybrominated diphenyl ethers (PBDEs) and three hexabromocyclododecane (HBCD) isomers (α-, ß- and γ-HBCD). PBDEs were observed in all samples tested and total PBDE concentrations ranged from 27ngg(-1) lipid to 130ngg(-1) lipid (geometric mean [GM] 46ngg(-1) lipid). ∑PBDE concentrations were significantly elevated in samples representing the 6-11year old age group (GM 65ngg(-1) lipid) relative to ages above 40years, although no difference in concentration was observed between the sexes. PBDE concentrations in Canadian sera from the general population were higher than reported in Europe and Asia, but a little lower than observed in the US. PBDE 47 was the greatest contributor to ∑PBDE concentrations and the GM concentration for this congener was 22ngg(-1) lipid. The other dominant contributors to ∑PBDE concentrations were in descending order: 153 [GM 9.4ngg(-1) lipid]>99 [GM 4.6ngg(-1) lipid]≅100 [GM 4.1ngg(-1) lipid]>209 [GM 1.1ngg(-1) lipid] and 183 [GM 0.42ngg(-1) lipid]. ∑HBCD was detected in all samples analysed, although most samples were observed at concentrations <1ngg(-1) lipid, similar to global concentrations. α-HBCD was the dominant contributor to ∑HBCD concentrations in Canadians although ß- and γ-HBCD were detected in 23% and 35% of the samples, respectively. No differences in ∑HBCD concentration were associated with age or sex. This dataset represents the first national data describing HBCD isomers and some PBDEs (e.g., 183, 209) in Canadians.

PCDD/F and PCB concentrations in sera from the Canadian Health Measures Survey (CHMS) from 2007 to 2009.

In order to establish a national baseline estimate of the concentrations of polychlorinated dibenzo-p-dioxins and dibenzofurans (PCDD/Fs) and polychlorinated biphenyls (PCBs) in Canadians, pooling of individual human sera was performed to ensure that a high frequency of detectable concentrations of analytes would be achieved. Nearly 5000 (4583) sera samples from Cycle 1 of the Canadian Health Measures Survey (CHMS) collected between 2007 and 2009 were used to form 59 composite pools of approximately 25 mL each. Pools were categorized by sex and age with participants ranging from 6 to 79 years. The pooled samples were analysed for 17 PCDD/Fs and 36 PCB congeners, and from these data, total toxic equivalent concentrations (TEQ(2005 PCDD/F+Dioxin-like [DL]-PCB)) were estimated. The average 2,3,7,8 tetrachlorodibenzodioxin (TCDD) concentration was <1 pg g⁻¹ on a lipid extractable basis. The average total TEQ(2005 PCDD/F+DL-PCB) was 11 pg TEQ g⁻¹ lipid and average ΣPCB concentrations were about 100 ng g⁻¹ lipid. Sex did not affect the concentrations, while PCB and PCDD/F concentrations were positively correlated with age (p<0.001). It appeared in some cases that the age group 6-11 years had higher concentrations of these persistent organic pollutants (POPs) than the concentrations observed in 12-19 year olds, however, the results were not statistically significant based on pair-wise comparisons. Concentration levels and patterns observed in this study of Canadians were similar to those reported in the US and European populations.