RESUMEN
Since the launch of the Chemicals Management Plan (CMP) in 2006, Health Canada has initiated screening-level risk assessments (RAs) of approximately 4300 priority substances under the Canadian Environmental Protection Act, 1999 (CEPA). With the availability of nationally representative human biomonitoring (HBM) data, over 300 of these substances were assessed using HBM-based RA approaches. Qualitative and quantitative HBM-based RA approaches for the regulatory risk assessment of the general population of Canada were developed to increase the efficiency of screening the potential health risk of CMP priority substances. To support HBM-based RAs, several biomonitoring equivalents (BE) were derived to interpret HBM data. For some CMP substances, Health Canada conducted cumulative risk assessments of chemical mixtures using HBM data as measures of exposure. In 2023, CEPA was amended to include the assessment of populations who may be disproportionately impacted (vulnerable populations) and the cumulative effects of multiple chemicals. Going forward, Health Canada is exploring modern approaches in HBM-based RAs, including biomarkers of effect and non-traditional biomarkers (e.g., hair, nails) to address CEPA amendments. This manuscript will discuss Health Canada's progress in HBM-based RAs, and the possible path forward in using HBM data to strengthen human health risk assessments.
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Monitoreo Biológico , Humanos , Medición de Riesgo , Canadá , Monitoreo Biológico/métodos , Contaminantes Ambientales/análisis , Contaminantes Ambientales/toxicidad , Exposición a Riesgos Ambientales/efectos adversos , Biomarcadores , Monitoreo del Ambiente/métodosRESUMEN
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.
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Monitoreo Biológico , Monitoreo del Ambiente , Humanos , Monitoreo del Ambiente/métodos , Salud Global , Salud PúblicaRESUMEN
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.
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Cerio , Metaloides , Metales de Tierras Raras , Canadá , Cromo , Humanos , Lantano , MetalesRESUMEN
Aluminium is widely used in many consumer products, however the primary source of aluminium exposure to the Canadian general population is through food. Aluminium can cause neurotoxicity and reproductive toxicity at elevated exposure levels. Health-based exposure guidance values have been established for oral exposure to aluminium, including a Minimal Risk Level (MRL) by the Agency for Toxic Substances and Disease Registry (ATSDR), a Provincial Tolerable Weekly Intake (PTWI) by the Joint FAO/WHO Expert Committee on Food Additives (JECFA) and a Tolerable Weekly Intake (TWI) by the European Food Safety Authority (EFSA). Aluminium concentration in blood and urine can be used as a tool for exposure characterization in a population. A pharmacokinetic (PK) model was developed based on human dosing data to derive blood Biomonitoring Equivalents (BEs), whereas a mass balance approach was used to derive urine BEs for the above guidance values. The BEs for blood for daily intake consistent with the MRL, PTWI and TWI were 18, 16 and 8 µg/L, respectively. BEs for urine for the same guidance values were 137, 123 and 57 µg/L, respectively. The derived BEs may be useful in interpreting population-level biomonitoring data in a health risk context and thereby screening and prioritizing substances for human health risk assessment and risk management.
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Aluminio/sangre , Aluminio/orina , Monitoreo Biológico/métodos , Aluminio/farmacocinética , Relación Dosis-Respuesta a Droga , Inocuidad de los Alimentos , Humanos , Modelos Biológicos , Medición de RiesgoRESUMEN
Bismuth (Bi) is a natural element present in the environmental media. Bismuth has been used medicinally for centuries, specifically for the treatment of gastrointestinal (GI) disorders. Although bismuth toxicity is rare in humans, an outbreak of bismuth-induced neurotoxicity was reported in France and Australia in the mid-1970s. The primary source of bismuth exposure in the general population is via food. US FDA (2019) estimated recommended daily intake (RDI) for bismuth as 848 mg bismuth/day (12.1 mg Bi/kg-d assuming a body weight of 70 kg) for GI tract disorders. Exposures to bismuth can be quantified by measuring concentrations in blood and urine. Biomonitoring equivalents (BEs) were derived based on US FDA's RDI as a tool for interpretation of population-level biomonitoring data. A regression between steady state plasma concentrations and oral intakes was used to derive plasma BEs. A whole blood: plasma partitioning coefficient of 0.6 was used to convert plasma BE into whole blood BE. A mass balance equation with a urinary excretion fraction of 0.0003 was used to derive urinary BE. The BE values associated with US FDA's RDI for plasma, whole blood and urine were 8.0, 4.8 and 0.18 µg/L, respectively. These BE values together with bismuth biomonitoring data may be used in screening and prioritization of health risk assessment of bismuth in the general population.
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Monitoreo Biológico , Bismuto/sangre , Bismuto/orina , Bismuto/efectos adversos , Humanos , Medición de Riesgo , Estados Unidos , United States Food and Drug AdministrationRESUMEN
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⯵g/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⯵g/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.
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Monitoreo Biológico , Exposición a Riesgos Ambientales/análisis , Zinc/análisis , Femenino , Humanos , Masculino , Medición de Riesgo , Distribución Tisular , Zinc/metabolismo , Zinc/farmacocinéticaRESUMEN
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⯵g/L, respectively) and children (50, 80, 580 and 360⯵g/L, respectively). The population median UIC values from NHANES and CHMS for adults (140-181, 122-126⯵g/L, respectively) and children (232, 189⯵g/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.
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Monitoreo del Ambiente/normas , Yodo/normas , Yodo/orina , Adolescente , Adulto , Niño , Preescolar , Dieta , Femenino , Humanos , Lactante , Recién Nacido , Yodo/farmacocinética , Masculino , Persona de Mediana Edad , Nivel sin Efectos Adversos Observados , Ingesta Diaria Recomendada , Adulto JovenRESUMEN
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.
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Bario/sangre , Bario/orina , Animales , Creatinina/orina , Exposición a Riesgos Ambientales , Monitoreo del Ambiente , Humanos , Encuestas Nutricionales , Valores de Referencia , Medición de RiesgoRESUMEN
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.
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Monitoreo del Ambiente/métodos , Canadá , Contaminantes Ambientales/análisis , Contaminantes Ambientales/toxicidad , Humanos , Medición de RiesgoRESUMEN
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.
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Monitoreo del Ambiente , Estaño/orina , Adolescente , Animales , Niño , Femenino , Humanos , Masculino , Ratas , Estaño/administración & dosificación , Estaño/farmacocinéticaRESUMEN
Silver is widely used as an antimicrobial agent in both ionic and nanoparticle forms, and general population exposure to silver can occur through the presence of trace levels in foods and dusts, through dermal contact with treated textiles, from use of wound care products, and other sources. Biomonitoring for silver in blood or urine in persons in the general population is being conducted by the Canadian Health Measures Survey (CHMS). Tolerable exposure guidance values for silver designed to prevent adverse effects of excess exposure are available from the United States Environmental Protection Agency (an oral reference dose, or RfD), from the United States Food and Drug Administration (a draft provisional tolerable intake, or TI) and from literature evaluations of recent data on responses to nanoparticle silver (a recommended tolerable daily intake, or TDI). A current physiologically-based pharmacokinetic model is used to estimate Biomonitoring Equivalents (BEs) for silver, which are steady-state biomarker concentrations consistent with the RfD, provisional TI, or recommended TDI (BERfD, BETI, or BETDI, respectively). The BE values based on silver in whole blood range from 0.2 to 0.9µg/L. BE values for silver in urine were not derived due to low confidence in the predicted steady-state urinary silver excretion rates. Comparison of general population biomonitoring data from Canada to the derived BE values indicate that general population exposure levels are generally below levels consistent with current risk assessment-derived exposure guidance values.
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Contaminantes Ambientales , Nanopartículas del Metal , Modelos Biológicos , Plata , Adulto , Canadá , Monitoreo del Ambiente , Contaminantes Ambientales/análisis , Contaminantes Ambientales/farmacocinética , Contaminantes Ambientales/toxicidad , Humanos , Nanopartículas del Metal/análisis , Nanopartículas del Metal/toxicidad , Medición de Riesgo , Plata/análisis , Plata/farmacocinética , Plata/toxicidadRESUMEN
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.