Sixth Report on Human Biomonitoring of Environmental Chemicals in Canada

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Results of the Canadian Health Measures Survey Cycle 6 (2018–2019)

Table of Contents

• 1 Introduction
• 2 Objectives
• 3 Survey design
  • 3.1 Target population
  • 3.2 Sample size and allocation
  • 3.3 Sampling strategy
    • 3.3.1 Sampling of collection sites
    • 3.3.2 Dwelling and participant sampling
  • 3.4 Selection of environmental chemicals
  • 3.5 Ethical considerations
• 4 Fieldwork
• 5 Laboratory analyses
  • 5.1 Metals and trace elements
    • 5.1.1 Blood analyses
    • 5.1.2 Urine analyses
  • 5.2 Self-care and consumer product chemicals
    • 5.2.1 Bisphenol A
    • 5.2.2 Parabens
  • 5.3 Cotinine
    • 5.3.1 Urine analysis
    • 5.3.2 Serum analysis
  • 5.4 Acrylamide
  • 5.5 Perfluoroalkyl and polyfluoroalkyl substances
  • 5.6 Pesticides
    • 5.6.1 Organophosphate pesticides
    • 5.6.2 Pyrethroids
    • 5.6.3 Ethylene bisdithiocarbamates
    • 5.6.4 ortho-Phenylphenol
  • 5.7 Plasticizers
    • 5.7.1 Phthalates
    • 5.7.2 Di(isononyl)cyclohexane-1,2-dicarboxylate (DINCH) and tri-(2-ethylhexyl) trimellitate (TEHT)
    • 5.7.3 2,2,4-Trimethyl-1,3-pentanediol diisobutyrate (TXIB) and cyclohexane-1,2-dicarboxylic acid (CHDA)
  • 5.8 Creatinine
• 6 Statistical data analyses
  • 6.1 Data modification and corrections
• 7 Considerations for interpreting the biomonitoring data
• 8 Summaries and results for metals and trace elements
  • 8.1 Lead
  • 8.2 Arsenic
  • 8.3 Boron
  • 8.4 Cadmium
  • 8.5 Chromium
  • 8.6 Mercury
  • 8.7 Selenium
• 9 Summaries and results for self-care and consumer product chemicals
  • 9.1 Bisphenol A
  • 9.2 Parabens
• 10 Summary and results for nicotine
  • 10.1 Nicotine
• 11 Summary and results for acrylamide
  • 11.1 Acrylamide
• 12 Summary and results for perfluoroalkyl and polyfluoroalkyl substances
  • 12.1 Perfluoroalkyl and polyfluoroalkyl substances
• 13 Summaries and results for pesticides
  • 13.1 Organophosphate pesticides
  • 13.2 Pyrethroids
  • 13.3 Ethylene bisdithiocarbamates
  • 13.4 ortho-Phenylphenol
• 14 Summaries and results for plasticizers
  • 14.1 Phthalates
  • 14.2 Di(isononyl)cyclohexane-1,2-dicarboxylate (DINCH)
  • 14.3 2,2,4-Trimethyl-1,3-pentanediol diisobutyrate (TXIB)
  • 14.4 Tri-(2-ethylhexyl) trimellitate (TEHT)
• Appendix A: Limits of detection
• Appendix B: Conversion factors
• Appendix C: Creatinine

Suggested citation:

Health Canada (2021): Sixth report on human biomonitoring of environmental chemicals in Canada. Minister of Health, Ottawa, ON. Available: https://www.canada.ca/en/health-canada/services/environmental-workplace-health/reports-publications/environmental-contaminants/sixth-report-human-biomonitoring.html

1 Introduction

These data tables present national data on concentrations of environmental chemicals in Canadians. The data were collected as part of an ongoing national direct health measures survey called the Canadian Health Measures Survey (CHMS). Statistics Canada, in partnership with Health Canada and the Public Health Agency of Canada, launched the CHMS in 2007 to collect health and wellness data and biological specimens from a nationally representative sample of Canadians. Biological specimens were analyzed for indicators of health status, chronic and infectious diseases, nutritional status and environmental chemicals.

The CHMS biomonitoring component measures many environmental chemicals and/or their metabolites in the blood and urine of survey participants. An environmental chemical can be defined as a chemical substance, either human-made or natural, that is present in the environment and to which humans may be exposed through media such as air, water, food, soil, dust or consumer products.

Data from previous cycles have been published in 5 Health Canada reports. The most recent report, the Fifth Report on Human Biomonitoring of Environmental Chemicals in Canada, was published in November 2019 (HC, 2019). Data from environmental chemicals measured in pooled serum collected from Canadians between 2007 and 2017 were published by Health Canada in December 2020 (HC, 2020). During the first 5 cycles, data were collected for approximately 200 environmental chemicals in individual samples and 90 environmental chemicals in pooled serum samples.

Data for cycle 6 were collected between January 2018 and December 2019 from approximately 5,700 Canadians aged 3–79 at 16 sites across Canada. Cycle 6 included 79 environmental chemicals, all of which have been measured in previous cycles.

A summary of the environmental chemicals measured in the blood and/or urine of individual respondents in the first 6 cycles of the CHMS is presented in Table 1.1.

The COVID-19 outbreak delayed the collection of data for cycle 7 of the CHMS. Collection is now anticipated to begin in 2022. Planning for future cycles is underway.

This report describes the general CHMS survey design and implementation, with emphasis on the biomonitoring component. These sections are followed by descriptive summaries for each chemical, outlining the chemical's identity, common uses, occurrence in the environment, potential sources of exposure in the human population, toxicokinetics and health effects, and Canadian regulatory status. For more information on trends in chemical concentrations measured as part of the CHMS, as well as comparisons with other biomonitoring initiatives, please refer to chemical-specific biomonitoring fact sheets available on the Human Biomonitoring Resources web page.

Throughout this report, data tables specific to each chemical are provided below the relevant text. The tables are broken down by age group and sex, and contain descriptive statistics on the distribution of blood and/or urine concentrations in the Canadian population. Data from all cycles are presented together in tables for ease of comparison. For chemicals measured only in previous cycles and/or in pooled serum, data can be found in previous reports (HC, 2010; 2013; 2015; 2017; 2019; 2020). Downloadable tables are available in comma-separated values (CSV) format through the Government of Canada's Open data portal.

References

HC (Health Canada) (2010). Report on Human Biomonitoring of Environmental Chemicals in Canada: Results of the Canadian Health Measures Survey Cycle 1 (2007–2009). Minister of Health, Ottawa, ON. Retrieved September 1, 2011.

HC (Health Canada) (2013). Second Report on Human Biomonitoring of Environmental Chemicals in Canada: Results of the Canadian Health Measures Survey Cycle 2 (2009–2011). Minister of Health, Ottawa, ON. Retrieved May 30, 2013.

HC (Health Canada) (2015). Third Report on Human Biomonitoring of Environmental Chemicals in Canada: Results of the Canadian Health Measures Survey Cycle 3 (2012–2013). Minister of Health, Ottawa, ON. Retrieved June 10, 2016.

HC (Health Canada) (2017). Fourth Report on Human Biomonitoring of Environmental Chemicals in Canada: Results of the Canadian Health Measures Survey Cycle 4 (2014–2015). Minister of Health, Ottawa, ON. Retrieved October 19, 2018.

HC (Health Canada) (2019). Fifth Report on Human Biomonitoring of Environmental Chemicals in Canada: Results of the Canadian Health Measures Survey Cycle 5 (2016–2017). Minister of Health, Ottawa, ON. Retrieved December 14, 2020.

HC (Health Canada) (2020). Report on Human Biomonitoring of Environmental Chemicals in Pooled Samples: Results of the Canadian Health Measures Survey Cycles 1 (2007–2009), 3 (2012–2013), 4 (2014–2015) and 5 (2016–2017). Minister of Health, Ottawa, ON. Retrieved January 15, 2021.

2 Objectives

The primary purpose of the biomonitoring component of the Canadian Health Measures Survey (CHMS) is to provide human biomonitoring data to scientists and health and environment officials to help them assess Canadians' exposure to environmental chemicals and develop policies to reduce exposure to toxic chemicals for the protection of their health.

Some specific uses of the CHMS biomonitoring data include:

• establishing baseline concentrations of chemicals in Canadians that allow for comparisons with subpopulations in Canada and with populations in other countries
• establishing baseline concentrations of chemicals to track trends in Canadians over time
• providing information for setting priorities and taking action to reduce Canadians' exposure to environmental chemicals and protect their health
• assessing the effectiveness of health and environmental risk management actions intended to reduce exposures and health risks from specific chemicals
• supporting research on the potential links between exposure to certain chemicals and specific health effects
• contributing to international monitoring programs, such as the Stockholm Convention on Persistent Organic Pollutants

3 Survey design

The Canadian Health Measures Survey (CHMS) was designed as a cross-sectional survey to address important data gaps and limitations in existing health information in Canada. Its principal objective is to collect national-level baseline data on important indicators of Canadians' health status, including those pertaining to exposures to environmental chemicals. This information is important in understanding exposure risk factors, detecting emerging trends in risk factors and exposures, and advancing health surveillance and research in Canada. Detailed descriptions of the CHMS rationale, survey design, sampling strategy and mobile examination centre (MEC) operations and logistics for cycle 6 have been published (Mather, 2020; StatCan, 2021).

3.1 Target population

Cycle 6 of the CHMS targets the population aged 3–79 living in one of the 10 provinces. The following groups were excluded from the survey: persons living in the 3 territories; persons living on reserves and other Indigenous settlements in the provinces; full-time members of the Canadian Forces; the institutionalized population; and residents of certain remote regions. Altogether, these exclusions represent approximately 3% of the target population.

Although the CHMS is not able to provide representative data for the entire Canadian population, a number of surveys and research projects are carried out in partnership with Health Canada that directly target some of these population gaps.

The First Nations Biomonitoring Initiative (FNBI) is a survey carried out by the Assembly of First Nations (AFN) and Health Canada that seeks to establish baseline biomonitoring data for First Nations people living on-reserve south of the 60° parallel (AFN, 2013). Between 2009 and 2011, the FNBI measured the levels of 97 environmental chemicals in blood and urine samples collected from 503 participants living in 13 First Nations communities across Canada. The complete report has been published by the AFN.

In addition, numerous biomonitoring studies have been undertaken in Canada's North through the Northern Contaminants Program (NCP). The NCP, which is managed by federal government departments, provincial and territorial agencies, and Indigenous organizations, was established in 1991 to respond to concerns about human exposure to contaminants in the traditional diets of Northern Indigenous peoples. The NCP provides funding for numerous individual studies undertaken in various regions of the North, including the Northwest Territories, Nunavut and Nunavik (Québec's North). More detailed information and results from these studies have been summarized in the Canadian Arctic Contaminants Assessment Reports and numerous scientific articles.

3.2 Sample size and allocation

To meet the objective of producing reliable estimates at the national level by age group and sex, cycle 6 of the CHMS required a minimum sample of at least 5,700 participants over a 2-year period. The participants were distributed among age groups (3–5, 6–11, 12–19, 20–39, 40–59 and 60–79 years) and sex (except for 3–5 years), for a total of 11 groups. For the 3–5-year age group, the survey was not designed to provide estimates for the individual sexes.

3.3 Sampling strategy

To meet the requirements of the CHMS, a multistage sampling strategy was used.

3.3.1 Sampling of collection sites

The CHMS required participants to report to a MEC and be able to travel to it within a reasonable period of time. For cycle 6, Census geography was used to create 425 collection sites across the country. A geographic area with a population of at least 10,000 and a maximum participant travel distance of 50 km in urban areas and 75 km in rural areas was required for the location of collection sites. Areas not meeting these criteria were excluded.

Including a larger number of collection sites with few respondents would have optimized the precision of the estimates. However, the logistical and cost constraints associated with the use of MECs restricted the number of collection sites to 16. The 16 collection sites were selected from within the 5 standard regional boundaries used by Statistics Canada (the Atlantic provinces, Québec, Ontario, the Prairies and British Columbia) and were allocated to these regions in proportion to population size. Although not every province in Canada had a collection site, the CHMS sites were chosen to represent the Canadian population in all 10 provinces, including larger and smaller population densities. The collection sites selected for cycle 6 of the CHMS are listed in Table 3.3.1.1.

3.3.2 Dwelling and participant sampling

Within each site, the most recent version of Statistics Canada's Household Survey Frame and more current information from other administrative sources were used to select dwellings and identify the birth dates of household members. Dwellings with known household composition at the time of the sample selection were stratified by age of household residents at the time of the survey, with the 6 age-group strata corresponding to the CHMS cycle 6 age groups (3–5, 6–11, 12–19, 20–39, 40–59 and 60–79 years). Within each site, a simple random sample of dwellings was selected in each stratum. Each selected dwelling was then contacted and asked to provide a list of current household members; this list was used to select the survey participants. One or 2 people were selected, depending on the household composition.

3.4 Selection of environmental chemicals

A series of formal and informal consultations were carried out to determine the set of environmental chemicals measured in cycle 6 of the CHMS. The consultations included stakeholders with expertise or interest in human biomonitoring of environmental chemicals. Key participants were various internal Health Canada branches and programs as well as a number of external groups, including other federal departments, provincial/territorial health and environment departments, industry groups, environment and health non-governmental organizations and academics.

The following criteria were used as general guides for identifying and selecting the environmental chemicals to include in the CHMS:

• seriousness of known or suspected health effects related to the substance
• need for public health actions related to the substance
• level of public concern about exposures and possible health effects related to the substance
• evidence of exposure of the Canadian population to the substance
• feasibility of collecting biological specimens in a national survey and associated burden on survey participants
• availability and efficiency of laboratory analytical methods
• costs of performing the test
• parity of selected chemicals with other national and international surveys and studies
• known data gaps
• commitments under national and international treaties, conventions and agreements
• current and anticipated health policy development and implementation
• volume of biospecimens available from survey

A full list of the chemicals measured in the blood and/or urine of individual respondents in CHMS cycle 6 is presented in Table 3.4.1.

Owing to the high cost of laboratory analyses, some environmental chemicals were not measured for all CHMS participants in cycle 6. The majority of the environmental chemicals were measured in a target subsample of approximately 2,500 participants aged 3–79 (Table 3.4.2), with the following exceptions: lead, cadmium, total mercury and selenium in blood were measured in approximately 4,500 participants; methylmercury and inorganic mercury were measured only in participants aged 3–19; cotinine in urine was measured in participants aged 6–79; and cotinine in serum was measured in all participants aged 6–79. Further details on the subsampling for environmental chemicals are available in the Canadian Health Measures Survey (CHMS) Data User Guide: Cycle 6 (StatCan, 2021) and in Sampling documentation for cycle 6 of the Canadian Health Measures Survey (Mather, 2020).

3.5 Ethical considerations

Personal information collected through the CHMS is protected under the federal Statistics Act (Canada, 1970-71-72). Under the act, Statistics Canada is obliged to safeguard and keep in trust the information it obtains from the Canadian public. Consequently, Statistics Canada has established a comprehensive framework of policies, procedures and practices to protect confidential information against loss, theft, unauthorized access, disclosure, copying or use; this includes physical, organizational and technological measures. The steps taken by Statistics Canada to safeguard the information collected in the CHMS have been described previously (Day et al., 2007).

Ethics approval for all components of the CHMS was obtained from the Health Canada and Public Health Agency of Canada Research Ethics Board. Informed written consent for the MEC portion of the CHMS was obtained from participants older than age 14. For younger children, a parent or legal guardian provided written consent, and children aged 6–13 provided assent. Participation in this survey was voluntary, and participants could opt out of any part of the survey at any time.

A strategy was developed to communicate results to survey participants with the advice and expert opinion of the CHMS Laboratory Advisory Committee, the Physician Advisory Committee, l'Institut national de santé publique du Québec (the reference laboratory performing some of the environmental chemical analyses) and Health Canada's Research Ethics Board (Day et al., 2007). For the environmental chemicals, only results for cadmium, lead and mercury were actively reported to participants from all sites. However, participants could receive all other test results upon request to Statistics Canada. More information on reporting to participants, including the ethical challenges encountered, can be found in Haines et al. (2011).

References

• AFN (Assembly of First Nations) (2013). First Nations Biomonitoring Initiative: National Results (2011). Assembly of First Nations, Ottawa, ON. Retrieved July 29, 2013.
• Mather, A. (2020). Sampling documentation for cycle 6 of the Canadian Health Measures Survey. Statistics Canada (internal document).
• Canada (1970-71-72). Statistics Act. c. 15, s. 1. Retrieved August 7, 2012.
• Day, B., Langlois, R., Tremblay, M., and Knoppers, B. (2007). Canadian Health Measures Survey: ethical, legal and social issues. Health Reports, Special Issue Supp. 18, 37–51.
• Haines, D.A., Arbuckle, T.E., Lye, E., Legrand, M., Fisher, M., Langlois, R., and Fraser, W. (2011). Reporting results of human biomonitoring of environmental chemicals to study participants: A comparison of approaches followed in two Canadian studies. Journal of Epidemiology and Community Health, 65(3), 191–198.
• StatCan (Statistics Canada) (2021). Canadian Health Measures Survey (CHMS) Data User Guide: Cycle 6. Ottawa, ON. Available upon request (infostats@canada.ca).

4 Fieldwork

Fieldwork for the Canadian Health Measures Survey (CHMS) cycle 6 took place over a period of 2 years, from January 2018 to December 2019. Data were collected sequentially at 16 sites across Canada. The sites were ordered to take into account seasonality by region and the temporal effect, subject to operational and logistical constraints.

Statistics Canada mailed advance letters and brochures to households that were selected as outlined in Section 3.3.2 of this report, Dwelling and participant sampling. The mailing informed potential participants that they would be contacted for the survey's data collection.

Data were collected from each consenting survey participant through a household personal interview, using a computer-assisted method, and through a visit to a mobile examination centre (MEC) for physical measures and biospecimen collection. The field team consisted of household interviewers and the CHMS MEC staff, including trained health professionals who performed the physical measures testing (StatCan, 2021).

Participants were first administered a household questionnaire in their homes. Using a computer application, the interviewer randomly selected 1 or 2 participants and conducted separate 45- to 60-minute health interviews (StatCan, 2019; 2021). The interviews collected demographic and socio-economic data, including information about lifestyle, medical history, current health status, smoking status, electronic cigarette use and neighbourhood environment. Participants were also informed that Statistics Canada would link the information collected during the interview to information from the tax data of all members of their household. Within approximately 2 weeks of the home visit, participants visited the MECs. Each MEC consisted of 3 trailers linked by enclosed pedestrian walkways. One trailer was for reception and contained an administration area and an examination room; the second trailer contained a laboratory, a phlebotomy (blood collection) area and examination rooms; and the third trailer contained additional examination rooms. The MEC operated for 5 to 6 weeks at each site to complete approximately 350 visits (StatCan, 2021). MEC appointments averaged 2 hours. A parent or legal guardian accompanied children under the age of 14. To maximize response rates, participants who were unable or unwilling to go to the MEC were offered the option of a home visit by CHMS MEC staff members to perform some of the physical measures and the biospecimen collection portion of the survey; there were 2 home visits in total in cycle 6 (StatCan, 2021).

At each MEC visit, participants signed consent/assent forms prior to any testing, and in most cases provided a urine sample immediately thereafter. For logistical purposes, spot samples were collected rather than 24-hour urine samples. The urine samples were collected using first-catch urine. (To note, as an exception, mid-stream urine was collected in cycle 1.) Guidelines were provided to participants asking them to abstain from urinating 2 hours prior to their MEC visit. Samples were collected in 120 mL urine specimen containers.

Trained health professionals took physical health measurements, such as for height, weight, blood pressure and physical fitness. A series of screening questions were administered to participants to determine their eligibility for the various tests, including phlebotomy, based on pre-existing exclusion criteria (StatCan, 2021). Blood specimens were drawn by a certified phlebotomist; the maximum amount depended upon the age of the participant and consent to storage. The approximate volumes drawn with and without consent to storage from participants 3–5 years old were 25.0 mL and 22.0 mL; 6–11 years old, 40.0 mL and 37.0 mL; 12–13 years old, 58.0 mL and 38.0 mL; 14–19 years old, 72.0 mL and 44.0 mL; and 20–79 years old, 78.0 mL and 48.0 mL.

Standardized operating procedures were developed for the collection of blood and urine specimens, the processing and aliquoting procedures and the shipping of biospecimens to ensure adequate data quality and standardize data collection. All blood and urine specimens collected in the MEC were processed and aliquoted in the MEC. Blood and urine specimens were stored in the MEC in either the refrigerator or the freezer, depending on the test. All specimens were stored as soon as processing was complete to maintain sample integrity. A 4-hour time limit from the point of collection was set for blood samples to be processed and stored; however, for most samples, this was completed within 2 hours. Given specific pre-analytical requirements for chromium (VI) in red blood cells, a time limit of 3 hours was set for processing and storing the samples. Once a week, the specimens were shipped on dry ice or in monitored refrigerated conditions to the reference laboratory for analyses. A priority sequence for laboratory analyses was established in the event that an insufficient volume of biospecimen was collected for complete analyses of the environmental chemicals as well as for analyses of infectious diseases, nutritional status and chronic diseases.

To maximize the reliability and validity of the data and reduce systematic bias, the CHMS developed quality assurance and quality control protocols for all aspects of the fieldwork. Quality assurance for the MEC covered staff selection and training, instructions to respondents (pre-testing guidelines) and issues related to data collection. All staff had appropriate education and training for their respective positions. To ensure consistent measurement techniques, procedure manuals and training guides were developed in consultation with, and reviewed by, experts in the field. Quality control samples were evaluated for each site and consisted of field blanks and blind replicates. Three field blanks (deionized water) were analyzed per site for all analytes except acrylamide, chromium (VI) in red blood cells and cotinine in blood, and creatinine and cotinine in urine. Three pairs of blind replicates were assessed per site for all analytes. Blind controls were also evaluated for analytical methods for which the laboratory did not participate in an interlaboratory comparison program. Approximately 6 blind control samples were evaluated at every second site for cotinine in blood and for parabens, ethylene thiourea, ortho-phenylphenol, di(isononyl)cyclohexane-1,2-dicarboxylate (DINCH), 2,2,4-trimethyl-1,3-pentanediol diisobutyrate (TXIB) and tri-(2-ethylhexyl) trimellitate (TEHT) metabolites in urine. Approximately 3 blind control samples were evaluated at every second site for acrylamide in blood.

Field blanks were sent to the reference laboratories at the start of each site, and results were expeditiously returned directly to the laboratory coordinators at Statistics Canada. Blind replicate and blind control samples were sent to the reference laboratories with regular specimen shipments. Quality control sample results were sent to Statistics Canada's CHMS headquarters along with all other respondent results. If required, feedback was promptly provided to the relevant reference laboratory for review and remedial action.

Detailed descriptions of the CHMS MEC operations and logistics have been described previously in Bryan et al. (2007) and are presented in the Canadian Health Measures Survey (CHMS) Data User Guide: Cycle 6 (StatCan, 2021).

References

• Bryan, S.N., St-Denis, M., and Wojitas, D. (2007). Canadian Health Measures Survey: Operations and logistics. Health Reports, Special Issue Supp. 18, 53–70.
• StatCan (Statistics Canada) (2019). Canadian Health Measures Survey (CHMS) – Detailed information for January 2018 to December 2019 (Cycle 6). Ottawa, ON. Retrieved March 19, 2021.
• StatCan (Statistics Canada) (2021). Canadian Health Measures Survey (CHMS) Data User Guide: Cycle 6. Ottawa, ON. Available upon request (infostats@canada.ca).

5 Laboratory analyses

Laboratory analyses of environmental chemicals and creatinine were performed at analytical laboratories within Health Canada and at l'Institut national de santé publique du Québec (INSPQ). Laboratories developed standardized operating procedures for the analytical methods used to measure environmental chemicals or their metabolites in biological samples. Analytical accuracy and the precision of measurements were evaluated through rigorous method validation programs at each laboratory.

To ensure ongoing accuracy and precision of results, several quality control measures were employed as part of the Canadian Health Measures Survey (CHMS). Field blanks were used to confirm that samples had not been contaminated during collection, processing, storage or shipping. Blind replicate samples were used as indicators of the precision of sample analysis, while blind control samples were used as indicators of the accuracy of sample analysis. Laboratories also participated in external quality control programs and interlaboratory comparison studies, as outlined in the sections below. The methods used in the analyses of the environmental chemicals and creatinine are described below.

5.1 Metals and trace elements

5.1.1 Blood analyses

5.1.1.1 Lead, cadmium, selenium, and total mercury

Analyses of lead, cadmium, selenium and mercury in whole blood were performed at the Centre de toxicologie du Québec (CTQ), INSPQ (INSPQ, 2018r). Briefly, whole blood samples were diluted in a basic solution containing octylphenol ethoxylate and ammonium hydroxide and analyzed for lead, cadmium, selenium and mercury using inductively coupled plasma mass spectrometry (ICP-MS). The ICP-MS method employed a Perkin Elmer Sciex Elan DRC II with an ESI SC-4 autosampler and an Elan workstation version 3.0. Matrix-matched calibration was performed using blood from non-exposed individuals. Internal quality control was ensured by analyzing 2 different reference materials from the Québec Multielement External Quality Assessment Scheme (QMEQAS) in each analysis sequence. The external quality and accuracy of the analytical method were assessed by participating in interlaboratory comparison programs, including the internal CTQ Programme de comparaisons interlaboratoires pour les métaux en milieu biologique (PCI); QMEQAS; the German External Quality Assessment Scheme (G-EQUAS); the U.S. Centers for Disease Control and Prevention's Lead and Multielement Proficiency Program; and the New York State Department of Health's Proficiency Program for Trace Elements in Whole Blood.

5.1.1.2 Chromium (VI)

Analyses of chromium (VI) in red blood cells were performed at the CTQ, INSPQ (INSPQ, 2018h). The analysis was an indirect measurement of chromium (VI) and was based on the fact that chromium (VI) is the only form of inorganic chromium that substantially penetrates cells. As such, chromium measured in red blood cells is attributed specifically to chromium (VI) exposure (Devoy et al., 2016).

Briefly, red blood cells were purified shortly after collection via a saline wash. Purified red blood cells were digested with concentrated nitric acid and hydrogen peroxide, and diluted in water to reduce viscosity and decrease the concentration of nitric acid. The samples were then analyzed using inductively coupled plasma tandem mass spectrometry (ICP-MS-MS). The ICP-MS-MS method employed an Agilent Technologies 8800 ICP-QQQ with a CETAC ASX-500 autosampler and a MassHunter 4.2 workstation version C.01.02. Terbium was used as an internal standard. Internal quality control was ensured by analyzing 3 different in-house reference materials (low, medium and high) in each analysis sequence.

5.1.1.3 Methylmercury and inorganic mercury

Analyses of methylmercury and inorganic mercury in whole blood were performed at the CTQ, INSPQ (INSPQ, 2018m). Briefly, whole blood samples were digested with tetramethylammonium hydroxide, and mercury species were derivatized into volatile compounds by sodium tetra-n-propylborate. Mercury was extracted in the gas phase by solid-phase microextraction with polydimethylsiloxane/divinylbenzene fibre. Ultimately, mercury species were analyzed using isotopic dilution in tandem gas chromatography and inductively coupled plasma mass spectrometry (ID-GC-ICP-MS). The ID-GC-ICP-MS method employed a Perkin Elmer Clarus 580 gas chromatograph with a Zebron ZB-5 column (Phenomenex), a CTC Analytics CombiPAL autosampler and an Empower chromatograph workstation version 3 alongside a Perkin Elmer NexION 350s ICP-MS with a Syngistix workstation version 1.1. Quantification was obtained by isotope dilution calculation. Internal quality control was ensured by analyzing 3 different in-house reference materials (low, medium and high) in each analysis sequence.

5.1.2 Urine analyses

5.1.2.1 Arsenic

Analyses of speciated arsenic in urine were performed at the CTQ, INSPQ (INSPQ, 2018j). The analyses measured arsenite (III), arsenate (V), monomethylarsonic acid, dimethylarsinic acid and the sum of arsenobetaine and arsenocholine. Briefly, urine samples were diluted tenfold in an ammonium carbonate solution (dilution solvent) compatible with the initial eluent, then analyzed on the high-performance liquid chromatography system, used in high pressure mode only, combined with inductively coupled plasma mass spectrometry (HPLC-ICP-MS). The HPLC-ICP-MS method employed a Waters ACQUITY HPLC with an Empower chromatograph workstation version 3 and a Perkin Elmer NexION 350s ICP-MS with a Syngistix workstation version 1.1. Methylseleno-L-cysteine was used as an internal standard. Internal quality control was ensured by analyzing 3 non-certified, in-house reference materials in each analysis sequence. External quality and the accuracy of the analytical method were assessed by participating in interlaboratory comparison programs, including the G-EQUAS.

 5.1.2.2 Boron

Analyses of boron in urine were performed at the CTQ, INSPQ (INSPQ, 2018g). Briefly, urine samples were diluted in 0.5% nitric acid and analyzed for boron using ICP-MS-MS. The ICP-MS-MS method employed an Agilent Technologies 8800 ICP-QQQ with a CETAC ASX-500 autosampler and a MassHunter 4.2 workstation version C.01.02. Beryllium was used as an internal standard. Internal quality control was ensured by analyzing 3 different in-house reference materials (low, medium and high) in each analysis sequence.

5.1.2.3 Cadmium

Analyses of cadmium in urine were performed at the CTQ, INSPQ (INSPQ, 2018s). Briefly, urine samples were diluted in 0.5% nitric acid and analyzed for cadmium using ICP-MS. The ICP-MS method employed a Perkin Elmer Sciex Elan DRC II with an ESI SC-4 autosampler and an Elan workstation version 3.0. Matrix-matched calibration was performed using urine from non-exposed individuals. Correction of molybdenum-based interference on cadmium concentrations was performed mathematically using equations derived following the addition of molybdenum to urine samples. Internal quality control was ensured by analyzing 3 different reference materials from the QMEQAS in each analysis sequence. The external quality and accuracy of the analytical method were assessed by participating in interlaboratory comparison programs, including the internal CTQ PCI, QMEQAS, G-EQUAS and New York State Department of Health's Proficiency Program for Trace Elements in Urine.

5.2 Self-care and consumer product chemicals

5.2.1 Bisphenol A

Analyses of bisphenol A in urine were performed at the CTQ, INSPQ (INSPQ, 2018f). Briefly, urine samples were hydrolyzed using β-glucuronidase and derivatized with pentafluorobenzyl bromide. The derivatized products were then extracted with a mixture of dichloromethane and hexane. Extracts were then evaporated and redissolved, and the sum of free and conjugated forms of bisphenol A was analyzed by gas chromatography coupled with tandem mass spectrometry (GC-MS-MS). The GC-MS-MS method employed an Agilent 6890 gas chromatograph with an Agilent 7683 automatic injector and sampler coupled to a Waters Quattro Micro-GC tandem quadrupole mass spectrometer and a workstation equipped with Waters MassLynx software version 4.1; measurements were carried out in multiple reaction monitoring (MRM) mode with a source in negative chemical ionization mode. Carbon-13–labelled bisphenol A analogues were used as internal standards. Internal quality control was ensured by analyzing 3 different in-house reference materials (low, medium and high) in each analysis sequence. The external quality and accuracy of the analytical method were assessed by participating in interlaboratory comparison programs, including the G-EQUAS.

5.2.2 Parabens

Analyses of parabens in urine were performed at the Food Program Western Region Laboratory, Health Canada, British Columbia, Canada (HC, 2017) using a method adapted from the U.S. Centers for Disease Control and Prevention (CDC, 2011). In these analyses, free and conjugated forms of butyl paraben, ethyl paraben, methyl paraben and propyl paraben were measured together. Briefly, urine samples were hydrolyzed using β-glucuronidase/sulfatase (Helix pomatia type H1). After enzymatic hydrolysis, samples were acidified with formic acid and preconcentrated using solid-phase extraction (Waters Oasis HLB SPE tubes). The sum of free and conjugated parabens was detected and quantified using ultra-performance liquid chromatography coupled with tandem mass spectrometry (UPLC-MS-MS). The UPLC-MS-MS method employed a Waters ACQUITY UPLC coupled to a Waters Quattro Premier XE tandem mass spectrometer; data were collected as MRM data in electrospray ionization-negative mode. Deuterated parabens (D4-methyl paraben, D4-ethyl paraben, D4-propyl paraben and D4-butyl paraben) were used as the internal standards. Internal quality control was ensured by analyzing 2 in-house quality control pools (low and high) in each batch of analyses.

5.3 Cotinine

5.3.1 Urine analysis

Analyses of free cotinine in urine were performed at the CTQ, INSPQ. One method was used for participants aged 6–11 (INSPQ, 2018c) and another for participants aged 12–79 (INSPQ, 2018e). Data from the 2 methods were combined and are presented separately for smokers aged 12–79 and non-smokers aged 6–79 for cycle 6. Briefly, for both methods, free cotinine was extracted from urine samples by solid-phase extraction via mixed cation-exchange and reverse-phase support on a Perkin Elmer JANUS automated liquid-handling workstation. The extracts were redissolved in the mobile phase and analyzed by UPLC-MS-MS. The UPLC-MS-MS method employed a Waters ACQUITY UPLC coupled to a Waters Xevo TQ-S or Quattro Premier XE tandem mass spectrometer and a workstation equipped with Waters MassLynx software version 4.1; measurements were carried out in MRM mode with an electrospray source-positive mode. For participants aged 12–79, within each analysis sequence, samples from non-smokers were analyzed first, followed by samples from smokers, to avoid contamination between samples. Deuterated cotinine was used as an internal standard. Internal quality control was ensured by analyzing 3 different in-house reference materials (low, medium and high) in each analysis sequence. The external quality and accuracy of the analytical method were assessed by participating in interlaboratory comparison programs, including the G-EQUAS.

5.3.2 Serum analysis

Analyses of free cotinine in serum were performed at the CTQ, INSPQ. One method was used for smokers (INSPQ, 2018a) and another for non-smokers (INSPQ, 2018b). Data from the 2 methods were combined and are presented separately for smokers and non-smokers. Briefly, for both methods, free cotinine was extracted from serum samples by solid-phase extraction via mixed cation-exchange and reverse-phase support on a Perkin Elmer JANUS automated liquid-handling workstation. The extracts were redissolved in the mobile phase and analyzed by UPLC-MS-MS. The UPLC-MS-MS method employed a Waters ACQUITY UPLC coupled to a Waters Xevo TQ-S micro tandem mass spectrometer and a workstation equipped with Waters MassLynx software version 4.1; measurements were carried out in MRM mode with an electrospray source-positive mode. Within each analysis sequence, samples from non-smokers were analyzed first, followed by samples from smokers, to avoid contamination between samples. Deuterated cotinine was used as an internal standard. Internal quality control was ensured by analyzing 3 different in-house reference materials (low, medium and high) in each analysis sequence.

5.4 Acrylamide

Analyses of acrylamide and glycidamide hemoglobin adducts in whole blood were performed at the Ontario Food Laboratory, Health Canada, Ontario, Canada (HC, 2014). Briefly, whole blood samples were reacted with modified Edman reagent (pentafluorophenyl isothiocyanate) and purified using solid-phase extraction on a column of ISOLUTE HM-N sorbent with a diisopropyl ether/ethyl acetate/toluene (50/40/10 v/v/v) eluent. The extract was evaporated, reconstituted and analyzed using UPLC-MS-MS. The UPLC-MS-MS method employed a Waters ACQUITY ultra-performance liquid chromatograph system coupled to a Waters Quattro Premier tandem mass spectrometer and a workstation equipped with MassLynx software; measurements were carried out in MRM mode with an Atmospheric Pressure Chemical Ionization positive ion mode. Carbon-13 labelled acrylamide octapeptide was used as an internal standard. Internal quality control was ensured by analyzing 2 different in-house reference materials (low and high) in each analysis sequence. Hemoglobin was also measured in whole blood using a commercial HemoCue assay kit; the hemoglobin value was used to adjust the acrylamide and glycidamide hemoglobin adduct results.

5.5 Perfluoroalkyl and polyfluoroalkyl substances

Analyses of perfluoroalkyl substances in plasma were performed at the CTQ, INSPQ (INSPQ, 2018k). The analyses measured perfluorobutanoic acid (PFBA), perfluorobutane sulfonate (PFBS), perfluorohexanoic acid (PFHxA), perfluorohexane sulfonate (PFHxS), perfluorooctane sulfonate (PFOS), perfluorooctanoic acid (PFOA), perfluorononanoic acid (PFNA), perfluorodecanoic acid (PFDA) and perfluoroundecanoic acid (PFUnDA). Briefly, plasma samples were extracted by solid-phase extraction with a WAX support on a Perkin Elmer JANUS automated liquid-handling workstation. The extracts were redissolved in the mobile phase and analyzed by UPLC-MS-MS. The UPLC-MS-MS method employed a Waters ACQUITY UPLC coupled to a Waters Xevo TQ-S tandem mass spectrometer and a workstation equipped with MassLynx software version 4.1; measurements were carried out in MRM mode with an electrospray ionization-negative mode. Internal quality control was ensured by analyzing 4 different reference materials — 3 in-house (low, medium and high) and 1 commercial — in each analysis sequence. External quality and accuracy of the analytical method was assessed by participating in interlaboratory comparison programs, including the internal CTQ Arctic Monitoring and Assessment Program ring test interlaboratory comparison program for persistent organic pollutants in human serum (PFHxA, PFHxS, PFNA, PFOA, PFOS, PFDA, PFUnDA) and the G-EQUAS for PFOS and PFOA.

5.6 Pesticides

5.6.1 Organophosphate pesticides

Analyses of dialkyl phosphate metabolites in urine were performed at the CTQ, INSPQ (INSPQ, 2018j). The analyses measured dimethylphosphate (DMP), dimethylthiophosphate (DMTP), dimethyldithiophosphate (DMDTP), diethylphosphate (DEP), diethylthiophosphate (DETP) and diethyldithiophosphate (DEDTP). Briefly, urine samples were hydrolyzed using β-glucuronidase and derivatized with pentafluorobenzyl bromide. The derivatized products were then extracted with a mixture of dichloromethane and hexane. Extracts were redissolved and analyzed by GC-MS-MS. The GC-MS-MS method employed an Agilent 6890 gas chromatograph with an Agilent 7683 automatic injector and sampler coupled to a Waters Quattro Micro-GC tandem quadrupole mass spectrometer and a workstation equipped with Waters MassLynx software version 4.1; measurements were carried out in MRM mode with a source in negative chemical ionization mode. Isotopically labelled dialkyl phosphate metabolite analogues were used as internal standards. Internal quality control was ensured by analyzing 4 different reference materials — 3 in-house (low, medium and high) and 1 commercial — in each analysis sequence. External quality and accuracy of the analytical method was assessed by participating in interlaboratory comparison programs, including the G-EQUAS.

5.6.2 Pyrethroids

Analyses of pyrethroids in urine were performed at the CTQ, INSPQ (INSPQ, 2018o). The analyses measured 3-phenoxybenzoic acid (3-PBA), 4-fluoro-3-phenoxybenzoic acid (4-F-3-PBA), cis-3-(2,2-dibromovinyl)-2,2-dimethylcyclopropane carboxylic acid (cis-DBCA), cis-3-(2,2-dichlorovinyl)-2,2-dimethylcyclopropane carboxylic acid (cis-DCCA), and trans-3-(2,2-dichlorovinyl)-2,2-dimethylcyclopropane carboxylic acid (trans-DCCA). Briefly, urine samples were hydrolyzed using β-glucuronidase and then acidified and extracted with hexane. The extracts were derivatized with hexafluoro-2-propanol (HFIP) and diisopropylcarbodiimide (DIC), and re-extracted with hexane. Extracts were then analyzed by GC-MS. The GC-MS method employed an Agilent 6890 network gas chromatograph with an Agilent 7683B automatic injector and sampler coupled to an Agilent 5975 mass spectrometer and a workstation equipped with Waters MassHunter software version B.07.01 build 7.1.524.0 and ChemStation G1701EA software version E02.01.1177; measurements were carried out in single ion monitoring modes following negative chemical ionization. Carbon-13 labelled trans-DCCA, 4-F-3-PBA and 3-PBA analogues were used as internal standards; the isotopically labelled trans-DCCA analogue was used as an internal standard for cis-DCCA, trans-DCCA and cis-DCBA. Internal quality control was ensured by analyzing 4 different reference materials — 3 in-house (low, medium and high) and 1 commercial — in each analysis sequence. External quality and accuracy of the analytical method was assessed by participating in interlaboratory comparison programs, including the G-EQUAS, for cis-DBCA, cis-DCCA, trans-DCCA and 3-PBA.

5.6.3 Ethylene bisdithiocarbamates

Analyses of total ethylene thiourea (ETU) in urine were performed at the CTQ, INSPQ (INSPQ, 2018i). Briefly, urine samples were hydrolyzed and derivatized with 2,3,4,5,6-pentafluorobenzyl bromide. The derivatized products were then extracted with hexane. The extracts were analyzed by UPLC-MS-MS. The UPLC-MS-MS method employed a Waters ACQUITY UPLC coupled to a Waters Xevo TQ-S tandem mass spectrometer and a workstation equipped with MassLynx software version 4.1; measurements were carried out in MRM mode with electrospray ionization positive mode. Deuterated ETU was used as an internal standard. Internal quality control was ensured by analyzing 4 different reference materials — 3 in-house (low, medium and high) and 1 commercial — in each analysis sequence.

5.6.4 ortho-Phenylphenol

Analyses of ortho-phenylphenol in urine were performed at the CTQ, INSPQ (INSPQ, 2018t). In these analyses, glucuronide- and sulfate-conjugated forms of ortho-phenylphenol were measured. Briefly, urine samples were extracted on an ion-exchange cartridge, eluted and evaporated to dryness. The extracts were redissolved in a mixture of methanol and demineralized water (25:75), then analyzed by UPLC-MS-MS. The UPLC-MS-MS method employed a Waters ACQUITY UPLC coupled to a Waters Xevo TQ-S tandem mass spectrometer and a workstation equipped with MassLynx software version 4.1; measurements were carried out in MRM mode with an electrospray ionization-negative mode. Carbon-13 labelled ortho-phenylphenol was used as an internal standard. Internal quality control was ensured by analyzing 3 different in-house reference materials (low, medium and high) in each analysis sequence.

5.7 Plasticizers

5.7.1 Phthalates

Analyses of phthalate metabolites in urine were performed at the CTQ, INSPQ (INSPQ, 2018n). The analyses measured 23 phthalate metabolites (see Table 3.4.1 for complete analyte list). Briefly, urine samples were hydrolyzed using β-glucuronidase, and the analytes were extracted using liquid–liquid extraction with a hexane:ethyl acetate solution (50:50) on a Perkin Elmer JANUS automated liquid-handling workstation. The extracts were analyzed by UPLC-MS-MS. The UPLC-MS-MS method employed a Waters ACQUITY UPLC coupled to a Waters Xevo TQ-S tandem mass spectrometer and a workstation equipped with MassLynx software version 4.1; measurements were carried out in MRM mode with an electrospray ionization-negative mode. Various internal standards were used, including deuterated monoisobutyl phthalate (MiBP) and carbon-13 labelled monobenzyl phthalate (MBzP), monocyclohexyl phthalate (MCHP), monoisononyl phthalate (MiNP), monoethyl phthalate (MEP), monomethyl phthalate (MMP), mono-n-butyl phthalate (MnBP), mono-n-octyl phthalate (MOP), mono(2-ethylhexyl) phthalate (MEHP), mono(2-ethyl-5-hydroxyhexyl) phthalate (MEHHP), mono(2-ethyl-5-oxohexyl) phthalate (MEOHP), mono(3-carboxypropyl) phthalate (MCPP), mono(2-ethyl-5-carboxypentyl) phthalate (MECPP) analogues and deuterated mono[2-(carboxymethyl)hexyl] phthalate (MCMHP), monoisodecyl phthalate (MiDP) and mono-3-hydroxy-n-butyl phthalate (3OH-MBP). In addition to MEHHP, the isotopically labelled MEHHP was used as an internal standard for mono-carboxy-n-heptyl phthalate (MCHpP), monocarboxyisononyl phthalate (MCiNP), mono(carboxyisooctyl) phthalate (MCiOP), monohydroxyisodecyl phthalate (MHiDP), monohydroxyisononyl phthalate (MHiNP), monooxoisodecyl phthalate (MOiDP) and monooxoisononyl phthalate (MOiNP). Internal quality control was ensured by analyzing 3 different in-house reference materials (low, medium and high) in each analysis sequence. External quality and accuracy of the analytical method was assessed by participating in interlaboratory comparison programs, including the G-EQUAS, for MEHHP, MEOHP, MECPP, MEHP, MnBP, MiBP and MBzP. Due to issues during the peak integration process, results were reported for MCiOP, MiNP and MCiNP semi-quantitatively. Results for all other analytes were reported quantitatively.

5.7.2 Di(isononyl)cyclohexane-1,2-dicarboxylate (DINCH) and tri-(2-ethylhexyl) trimellitate (TEHT)

Analyses of di(isononyl)cyclohexane-1,2-dicarboxylate (DINCH) and tri-(2-ethylhexyl) trimellitate (TEHT) metabolites in urine were performed at the CTQ, INSPQ (INSPQ, 2018p). The analyses measured the DINCH metabolites trans-cyclohexane-1,2-dicarboxylic mono isononyl ester (trans-MINCH), cyclohexane-1,2-dicarboxylic mono oxoisononyl ester (oxo-MINCH), cyclohexane-1,2-dicarboxylic mono hydroxyisononyl ester (OH-MINCH), cis-cyclohexane-1,2-dicarboxylic mono carboxyisononyl ester (cis-cx-MINCH) and trans-cyclohexane-1,2-diarboxylic mono carboxyisononyl ester (trans-cx-MINCH). The analyses also measured the TEHT metabolites 1-mono(2-ethylhexyl)trimellitate (1-MEHTM), 2-mono(2-ethylhexyl)trimellitate (2-MEHTM) and 4-mono(2-ethylhexyl)trimellitate (4-MEHTM). Briefly, urine samples were hydrolyzed using β-glucuronidase, and the analytes were extracted using liquid–liquid extraction with a 50:50 hexane:ethyl acetate solution on a Perkin Elmer JANUS automated liquid-handling workstation. The extracts were taken up with a mixture of acetonitrile and demineralized water and analyzed by UPLC-MS-MS. The UPLC-MS-MS method employed a Waters ACQUITY UPLC coupled to a Waters Xevo TQ-S tandem mass spectrometer and a workstation equipped with MassLynx software version 4.1; measurements were carried out in MRM mode with an electrospray ionization-negative mode. Deuterated trans-cx-MINCH was used as an internal standard for trans-cx-MINCH, cis-cx-MINCH, oxo-MINCH, 1-MEHTM, 2-MEHTM and 4-MEHTM. Deuterated trans-cyclohexane-1,2-dicarboxylic mono hydroxyisononyl ester (trans-OH-MINCH) was used as an internal standard for OH-MINCH, and deuterated trans-MINCH was used as an internal standard for trans-MINCH. Internal quality control was ensured by analyzing 3 different in-house reference materials (low, medium and high) in each analysis sequence.

5.7.3 2,2,4-Trimethyl-1,3-pentanediol diisobutyrate (TXIB) and cyclohexane-1,2-dicarboxylic acid (CHDA)

Analyses of cyclohexane-1,2-dicarboxylic acid (CHDA) and 2,2,4-trimethyl-1,3-pentanediol diisobutyrate (TXIB) metabolites in urine were performed at the CTQ, INSPQ (INSPQ, 2018q). The analyses measured the di(isononyl)cyclohexane-1,2-dicarboxylate (DINCH) metabolite CHDA and the TXIB metabolites 2,2,4-trimethyl-1,3-pentanediol (TMPD) and 2,2,4-trimethyl-3-hydroxy valeric acid (HTMV). Briefly, urine samples were hydrolyzed using β-glucuronidase and arylsulfatase, acidified and extracted with ethyl acetate on a Perkin Elmer JANUS automated liquid-handling workstation. The extracts were taken up with a mixture of methanol and water and analyzed by UPLC-MS-MS. The UPLC-MS-MS method employed a Waters ACQUITY UPLC coupled to a Waters Xevo TQ-S tandem mass spectrometer and a workstation equipped with MassLynx software version 4.1; measurements were carried out in MRM mode with an electrospray ionization-negative mode for HTMV and CHDA and positive mode for TMPD. Deuterated 2,2-bis(hydroxymethyl)pentane was used as an internal standard for TMPD. Deuterated HTMV and CHDA analogues were used as internal standards for HTMV and CHDA, respectively. Internal quality control was ensured by analyzing 3 different in-house reference materials (low, medium and high) in each analysis sequence.

5.8 Creatinine

Analyses of creatinine in urine were performed at the CTQ, INSPQ (INSPQ, 2018d) using the colorimetric end point Jaffe method. Briefly, urine samples were reacted with an alkaline solution of sodium picrate to form a red Janovski complex. The complex was analyzed by spectrophotometry at 510 nm. The method employed a Thermo Fischer Scientific Indiko Plus automatic analyzer and a workstation equipped with Indiko software version 5.3; measurements were carried out in kinetic mode. Internal quality control was ensured by analyzing 2 commercial reference materials in each analysis sequence. The external quality and accuracy of the analytical method were assessed by participating in interlaboratory comparison programs, including the College of American Pathologists Forensic Urine Drug Testing (Confirmatory) Survey.

References

• CDC (Centers for Disease Control and Prevention) (2011). Bisphenol A and other environmental phenols and Parabens in urine NHANES 2009–2010. Method No. 6301.01. National Center for Environmental Health, Centers for Disease Control and Prevention, Atlanta, GA. Retrieved January 22, 2019.
• Devoy, J., Géhin, A., Müller, S., Melczer, M., Remy, A., Antoine, G., and Sponne, I. (2016). Evaluation of chromium in red blood cells as an indicator of exposure to hexavalent chromium: An in vitro study. Toxicology Letters, 255, 63–70.
• HC (Health Canada) (2014). Determination of N-terminal hemoglobin adducts of acrylamide and glycidamide in whole blood by LC/MS/MS. Ontario Food Laboratory, Regions and Programs Bureau, Health Canada, Toronto, ON.
• HC (Health Canada) (2017). Analysis of parabens in human urine by UPLC MS MS. BC Food Laboratory. Regulatory Operations and Regions Branch, Health Canada, Vancouver, BC.
• INSPQ (Institut national de santé publique du Québec) (2018a). Méthode d'analyse pour doser la cotinine dans le sérum chez les fumeurs par UPLC-MS-MS (C-611-01), format condensé pour ECMS. Laboratoire de toxicologie, Québec, QC.
• INSPQ (Institut national de santé publique du Québec) (2018b). Méthode d'analyse pour doser la cotinine dans le sérum chez les non-fumeurs par UPLC-MS-MS (C-610-02), format condensé pour ECMS. Laboratoire de toxicologie, Québec, QC.
• INSPQ (Institut national de santé publique du Québec) (2018c). Méthode d'analyse pour doser la cotinine dans l'urine par UPLC-MS-MS méthode robotisée (C-550-G), format condensé pour ECMS. Laboratoire de toxicologie, Québec, QC.
• INSPQ (Institut national de santé publique du Québec) (2018d). Méthode d'analyse pour doser la créatinine dans l'urine par analyseur automatique Indiko Plus (C-601-02), format condensé pour ECMS. Laboratoire de toxicologie, Québec, QC.
• INSPQ (Institut national de santé publique du Québec) (2018e). Méthode d'analyse pour doser la nicotine et ses métabolites et l'anabasine dans l'urine par UPLC-MS-MS (C-569-E), format condensé pour ECMS. Laboratoire de toxicologie, Québec, QC.
• INSPQ (Institut national de santé publique du Québec) (2018f). Méthode d'analyse pour doser le bisphénol A (BPA) et le triclosan dans l'urine par GC-MS-MS (E-475-04), format condensé pour ECMS. Laboratoire de toxicologie, Québec, QC.
• INSPQ (Institut national de santé publique du Québec) (2018g). Méthode d'analyse pour doser le bore urinaire par spectrométrie de masse en tandem à plasma d'argon induit (ICP-MS-MS), Agilent 8800 (M-611-02), format condensé pour ECMS. Laboratoire de toxicologie, Québec, QC.
• INSPQ (Institut national de santé publique du Québec) (2018h). Méthode d'analyse pour doser le chrome hexavalent dans les globules rouges par spectrométrie de masse en tandem à plasma d'argon induit (ICP-MS-MS), Agilent 8800 (M-610-A), format condensé pour ECMS. Laboratoire de toxicologie, Québec, QC.
• INSPQ (Institut national de santé publique du Québec) (2018i). Méthode d'analyse pour doser le ETU total dans l'urine par UPLC-MS-MS (E-499-02), format condensé pour ECMS. Laboratoire de toxicologie, Québec, QC.
• INSPQ (Institut national de santé publique du Québec) (2018j). Méthode d'analyse pour doser les alkylphosphates dans l'urine par GC-MS-MS (E-495-04), format condensé pour ECMS. Laboratoire de toxicologie, Québec, QC.
• INSPQ (Institut national de santé publique du Québec) (2018k). Méthode d'analyse pour doser les composés perfluorés (PFC) dans le sérum / plasma par UPLC-MS-MS (E-501-03), format condensé pour ECMS. Laboratoire de toxicologie, Québec, QC.
• INSPQ (Institut national de santé publique du Québec) (2018l). Méthode d'analyse pour doser les espèces d'arsenic dans l'urine par chromatographie liquide haute pression Waters ACQUITY en tandem avec la spectrométrie de masse à plasma d'argon induit NexION 350s (HPLC-ICP-MS) (M-612-03), format condensé pour ECMS. Laboratoire de toxicologie, Québec, QC.
• INSPQ (Institut national de santé publique du Québec) (2018m). Méthode d'analyse pour doser les espèces de mercure dans le sang par dilution isotopique en chromatographie gazeuse en tandem avec la spectrométrie de masse à plasma d'argon induit NexION 350s (ID-GC-ICP-MS) (M-613-01), format condensé pour ECMS. Laboratoire de toxicologie, Québec, QC.
• INSPQ (Institut national de santé publique du Québec) (2018n). Méthode d'analyse pour doser les métabolites des phtalates dans l'urine par UPLC-MS-MS (E-490-05), format condensé pour ECMS. Laboratoire de toxicologie, Québec, QC.
• INSPQ (Institut national de santé publique du Québec) (2018o). Méthode d'analyse pour doser les métabolites des pyréthroïdes dans l'urine par GC-MS (E-491-04), format condensé pour ECMS. Laboratoire de toxicologie, Québec, QC.
• INSPQ (Institut national de santé publique du Québec) (2018p). Méthode d'analyse pour doser les métabolites du DINCH et du TOTM dans l'urine par UPLC-MS-MS (E-496-02), format condensé pour ECMS. Laboratoire de toxicologie, Québec, QC.
• INSPQ (Institut national de santé publique du Québec) (2018q). Méthode d'analyse pour doser les métabolites du TXIB et le CHDA dans l'urine par UPLC-MS-MS (E-497-02), format condensé pour ECMS. Laboratoire de toxicologie, Québec, QC.
• INSPQ (Institut national de santé publique du Québec) (2018r). Méthode d'analyse pour doser les métaux et autres éléments dans le sang par spectrométrie de masse à plasma d'argon induit (ICP-MS), DRC II (M-572-10), format condensé pour ECMS. Laboratoire de toxicologie, Québec, QC.
• INSPQ (Institut national de santé publique du Québec) (2018s). Méthode d'analyse pour doser les métaux et autres éléments dans l'urine par spectrométrie de masse à plasma d'argon induit (ICP-MS), DRC II (M-571-09), format condensé pour ECMS. Laboratoire de toxicologie, Québec, QC.
• INSPQ (Institut national de santé publique du Québec) (2018t). Méthode d'analyse pour doser l'ortho-phénylphénol-glucuronide et l'ortho-phénylphénol-sulfate dans l'urine par UPLC-MS-MS (E-503-A), format condensé pour ECMS. Laboratoire de toxicologie, Québec, QC.

6 Statistical data analyses

Descriptive statistics on the concentrations of environmental chemicals in the blood and urine of Canadians were generated using the Statistical Analysis System software (SAS Institute Inc., version 9.4, 2014) and the SUDAAN® (SUDAAN Release 11.0.3, 2018) statistical software package.

The Canadian Health Measures Survey (CHMS) is a sample survey. This means the participants represent many other Canadians who were not included in the survey. To ensure that the results would be representative of the entire population, sample weights were generated by Statistics Canada and incorporated into all estimates presented in the data tables. Survey weights were used to take into account the unequal probability of selection into the survey as well as non-response. Further, to account for the complex survey design of the CHMS, the set of bootstrap weights included with the data set was used to estimate the 95% confidence intervals (CIs) for all means, percentiles and detection frequencies (Rao et al., 1992; Rust and Rao, 1996). Further details on sample weights are available in the Canadian Health Measures Survey (CHMS) Data User Guide: Cycle 6 (StatCan, 2021).

Data tables are presented for each chemical measured in cycle 6. When available, data from previous cycles are also provided within the tables. In the first Report on Biomonitoring of Environmental Chemicals in Canada, all results were reported to 2 decimal places. For subsequent cycles of the CHMS the reporting protocol changed, and the results were reported to 2 significant digits. For consistency, cycle 1 data were adjusted to 2 significant digits before generating the descriptive statistics, and data from all cycles are presented to 2 significant digits. Therefore, the descriptive statistics presented for cycle 1 may differ from those presented in the first report. The differences are not significant, and the values presented in the first report are still considered to be accurate.

The data tables include the sample size (n); the percentage of the population with concentrations at or above the limit of detection (LOD), termed detection frequency; the geometric mean (GM); and the 10^th, 50^th, 90^th and 95^th percentiles, with associated 95% CIs. For each chemical, results are presented for the total population as well as by age group and sex. Measurements that fell below the LOD for the laboratory analytical method were assigned a value equal to half the LOD. If the proportion of results below the LOD was greater than 40%, GMs were not calculated. Percentile estimates that are less than the LOD are reported as <LOD. LOD values for each chemical are provided alongside their respective data tables and in Appendix A. Conversion factors to assist in the comparison of data from other studies that report different units are provided in Appendix B.

Chemicals measured in whole blood, plasma or serum are presented as weight of chemical per volume of a given blood matrix (µg chemical/L blood or plasma or serum). Data for hemoglobin adducts are presented as the amount of hemoglobin adduct per weight of hemoglobin (pmol adduct/g hemoglobin). Chromium (VI) measures in red blood cells are presented as weight of chromium per volume of red blood cells (µg/L red blood cells).

For urine measurements, concentrations are presented as weight of chemical per volume of urine (µg chemical/L urine) and adjusted for urinary creatinine (µg chemical/g creatinine). Urinary creatinine is a chemical by-product generated from muscle metabolism; it is frequently used to adjust for urine concentration (or dilution) in spot urine samples because its production and excretion are relatively constant over 24 hours owing to homeostatic controls (Barr et al., 2005; Boeniger et al., 1993; Pearson et al., 2009). If the chemical measured behaves similarly to creatinine in the kidney, it will be filtered at the same rate; thus, expressing the chemical per gram of creatinine helps adjust for the effect of urinary dilution as well as some differences in renal function and lean body mass (Barr et al., 2005; CDC, 2009; Pearson et al., 2009). Creatinine is primarily excreted by glomerular filtration; therefore, creatinine adjustment may not be appropriate for compounds that are excreted primarily by tubular secretion in the kidney (Barr et al., 2005; Teass et al., 2003). In addition, creatinine excretion can vary based on age, sex and ethnicity; therefore, it may not be appropriate to compare creatinine-adjusted concentrations among different demographic groups (e.g., children versus adults) (Barr et al., 2005). Where urinary creatinine values were missing or <LOD, the estimate of that participant's creatinine-adjusted chemical was not calculated and was also listed as missing.

Descriptive statistics are available for creatinine (mg/dL) (Appendix C). These include n; detection frequency; GM; the 10^th, 50^th, 90^th and 95^th percentiles; and associated 95% CIs for the total population as well as by age group and sex. Measurements that fell below the LOD for the laboratory analytical method were assigned a value equal to half the LOD.

Specific gravity was also measured in all urine samples immediately following sample collection at the mobile examination centre. Urinary specific gravity is the ratio of densities between urine and pure water, and can be used to adjust for variations in urine output, similar to urinary creatinine adjustment. Urinary specific gravity adjustment has not been presented for any of the chemicals; however, specific gravity data are available upon request by contacting Statistics Canada at infostats@canada.ca should researchers wish to perform this adjustment for their own data analyses.

Under the Statistics Act, Statistics Canada is required to ensure participant confidentiality. Therefore, estimates based on a small number of participants are suppressed. Following suppression rules for the CHMS, any estimate based on fewer than 10 participants is suppressed in the data tables. To avoid suppression, estimates at the 95^th percentile require at least 100 participants; estimates at the 10^th and 90^th percentiles require at least 50 participants; estimates at the 50^th percentile require at least 10 participants; and estimates of the GM require at least 5 participants.

Estimates from a sample survey will inevitably include sampling errors. Measuring the possible scope of sampling errors is based on the standard error of the estimates drawn from the survey results. To get a better indication of the size of the standard error, it is often more useful to express the standard error in terms of the estimate being measured. The resulting measure, called the coefficient of variation (CV), is obtained by dividing the standard error of the estimate by the estimate itself; it is expressed as a percentage of the estimate. This report uses the data quality symbol E adapted from Statistics Canada guidelines for releasing estimates based on their CVs. When a CV is greater than 16.6%, the estimate is identified by the superscript letter E and accompanied by a warning that cautions users of the high sampling variability associated with the estimate.

Previously, when a CV for an estimate was greater than 33.3%, the data were not published. To promote understanding of biomonitoring data and maximize its use, estimates are no longer suppressed based upon their CVs. Rather, users are encouraged to consider the confidence interval that accompanies each estimate as an indicator of the estimate's reliability. A narrow confidence interval closer to the estimate indicates lower sampling variability and greater reliability of the estimate. Conversely, a wider confidence interval further from the estimate indicates higher sampling variability and lower reliability of the estimate. Incorporating the confidence intervals alongside estimates is encouraged when using or reporting the data presented in this report.

6.1 Data modification and corrections

Certain data in the present report differ from what has appeared in previous CHMS biomonitoring reports; data modification and corrections include the following:

• previously suppressed data that had been replaced by the letter F in past reports are now published
• corrected cycle 5 data for lead, cadmium, mercury and selenium measured in blood
• corrected cycle 5 data for monohydroxyisononyl phthalate (MHiNP)
• corrected cycle 1 LODs for organophophate pesticide metabolites (see Appendix A)

References

• Barr, D.B., Wilder, L.C., Caudill, S.P., Gonzalez, A.J., Needham, L.L., and Pirkle, J.L. (2005). Urinary creatinine concentrations in the U.S. population: Implications for urinary biologic monitoring measurements. Environmental Health Perspectives, 113(2), 192–200.
• Boeniger, M.F., Lowry, L.K., and Rosenberg, J. (1993). Interpretation of urine results used to assess chemical exposure with emphasis on creatinine adjustments: A review. American Industrial Hygiene Association Journal, 54(10), 615–627.
• CDC (Centers for Disease Control and Prevention) (2009). Fourth National Report on Human Exposure to Environmental Chemicals. Department of Health and Human Services, Atlanta, GA. Retrieved June 28, 2019.
• Pearson, M., Lu, C., Schmotzer, B., Waller, L., and Riederer, A. (2009). Evaluation of physiological measures for correcting variation in urinary output: Implications for assessing environmental chemical exposure in children. Journal of Exposure Science and Environmental Epidemiology, 19(3), 336–342.
• Rao, J., Wu, C., and Yue, K. (1992). Some recent work on resampling methods for complex surveys. Survey Methodology, 18(2), 209–217.
• Rust, K.F., and Rao, J.N.K. (1996). Variance estimation for complex surveys using replication techniques. Statistical Methods in Medical Research, 5(3), 283–310.
• StatCan (Statistics Canada) (2021). Canadian Health Measures Survey (CHMS) Data User Guide: Cycle 6. Ottawa, ON. Available upon request (infostats@canada.ca).
• Teass, A., Biagini, R., DeBord, G., and DeLon Hull, R. (2003). Application of biological monitoring methods. NIOSH Manual of Analytical Methods, NIOSH Publication Number 2003–154(3).

7 Considerations for interpreting the biomonitoring data

The Canadian Health Measures Survey (CHMS) was designed to provide estimates of environmental chemical concentrations in blood or urine for the Canadian population as a whole. The first cycle of the survey covered approximately 96% of the Canadian population aged 6–79. The subsequent cycles included children as young as 3 years of age and covered approximately 96% to 97% of the Canadian population aged 3–79. The survey was not designed to permit breakdown of data by region, province or collection site, although some analysis is possible if data from more than 1 cycle are combined (see Instructions for Combining Multiple Cycles of Canadian Health Measures Survey [CHMS] Data [Statistics Canada, 2015]). In addition, the CHMS design did not target specific exposure scenarios; consequently, it did not select or exclude participants on the basis of their potential for low or high exposures to environmental chemicals.

Biomonitoring can estimate how much of a chemical is present in a person, but it cannot say what health effects, if any, may result from that exposure. The ability to measure environmental chemicals at very low concentrations has advanced in recent years. However, the presence alone of a chemical in a person's body does not necessarily mean that it will cause a health effect. Factors such as the dose, the toxicity of the chemical, and the duration and timing of exposure are important to determine whether potential adverse health effects may occur. For chemicals such as lead or mercury, research studies have provided a good understanding of the health risks associated with different concentrations in blood. However, for many chemicals, further research is needed to understand the potential health effects, if any, associated with different blood or urine concentrations. Furthermore, small amounts of certain chemicals, such as selenium, are essential for the maintenance of good health and would be expected to be present in the body. In addition, the way in which a chemical will act in the body will differ among individuals and cannot be predicted with certainty. Certain populations (children, pregnant women, the elderly, or immunocompromised people) may be more susceptible to the effects of exposure.

The absence of a chemical does not necessarily mean a person has not been exposed. It may be that the technology is not capable of detecting such a small amount, or that the exposure occurred at an earlier point in time, allowing for the chemical to be eliminated from the person's body before the measurement took place.

Biomonitoring cannot tell us the source or route of the exposure. The amount of chemical measured indicates the total amount that has entered the body through all routes of exposure (ingestion, inhalation, and skin contact) and from all sources (air, water, soil, food and consumer products). The detection of the chemical may be the result of exposure to a single source or multiple sources. In addition, in most cases, biomonitoring cannot distinguish between natural and anthropogenic sources. Many chemicals (lead, mercury, cadmium, and arsenic) occur naturally in the environment and are also present in human-made products.

While most metals are measured as the parent compounds, many other chemicals are measured as metabolites. For many chemicals, parent compounds may be broken down (i.e., metabolized) in the body into 1 or more metabolites. Some metabolites are specific to 1 parent compound, whereas others are common to several parent compounds. As well, several metabolites found in urine are also found in the environment as a result of other processes (e.g., dialkyl phosphate metabolites). Their presence in urine does not necessarily mean that an exposure to the parent chemical has occurred; rather, exposure could be to the metabolite itself in media such as food, water or air.

Factors that contribute to the concentrations of chemicals measured in blood and urine include the quantity entering the body through all routes of exposure, absorption rates, distribution to various tissues in the body, metabolism, and excretion of the chemical and/or its metabolites from the body. These processes, also called toxicokinetics, depend on both the characteristics of the chemical, including its solubility in fat (or lipophilicity), its pH, its particle size and the characteristics of the individual being exposed, such as age, diet, health status and ethnicity. For these reasons, the way in which a chemical will act in the body will differ among individuals and cannot be predicted with certainty.

The CHMS biomonitoring data currently available include temporal data for substances measured in individual participants in cycle 1 (2007–2009), cycle 2 (2009–2011), cycle 3 (2012–2013), cycle 4 (2014–2015), cycle 5 (2016–2017) and cycle 6 (2018–2019), as well as for measures in pooled serum in cycles 1, 3, 4 and 5 (2007–2017). Results from multiple cycles can be compared in order to examine trends in Canadians' exposures to selected environmental chemicals. It is important to note that some sampling and analytical modifications between cycles may have contributed some variation in results for those substances measured in multiple cycles. The limits of detection (LODs) for certain analytical methods have changed from cycle to cycle (Appendix A). Although the LOD values did not change by a large margin, this difference should be noted when comparing data from multiple cycles. In addition, the urine collection protocol and guidelines were changed in cycle 2, and this may have resulted in a shift in creatinine levels when cycle 1 data are compared with those from subsequent cycles. This, in turn, could affect creatinine-adjusted levels of some chemicals. For more information on trends in chemical concentrations measured as part of the CHMS, please refer to chemical-specific biomonitoring fact sheets available on the Human Biomonitoring Resources web page.

Urinary creatinine concentrations can also be affected by variables such as age, sex and ethnicity, resulting in differences among demographic groups within a single cycle (Mage et al., 2004). In particular, creatinine excretion per unit of body weight increases substantially with increasing age in children (Aylward et al., 2011; Remer et al., 2002). As a result, it is acceptable to compare creatinine-adjusted concentrations among similar demographic groups (e.g., children with children, adults with adults, males with males) but not among 2 different demographic groups (e.g., children versus adults, males versus females) (Barr et al., 2005).

More in-depth statistical analyses of the CHMS biomonitoring data — including time trends, exploring relationships among environmental chemicals, other physical measures and self-reported information — are being published by researchers in scientific literature. A bibliography of publications using CHMS data is available. CHMS data are available to scientists through Statistics Canada's Research Data Centres Program and are a resource for additional scientific analyses. Further information about the CHMS can be obtained by contacting Statistics Canada at infostats@canada.ca.

References

• Aylward, L.L., Lorber, M., and Hays, S.M. (2011). Urinary DEHP metabolites and fasting time in NHANES. Journal of Exposure Science and Environmental Epidemiology, 21(6), 615–624.
• Barr, D.B., Wilder, L.C., Caudill, S.P., Gonzalez, A.J., Needham, L.L., and Pirkle, J.L. (2005). Urinary creatinine concentrations in the U.S. population: Implications for urinary biologic monitoring measurements. Environmental Health Perspectives, 113(2), 192–200.
• Mage, D.T., Allen, R.H., Gondy, G., Smith, W., Barr, D.B., and Needham, L.L. (2004). Estimating pesticide dose from urinary pesticide concentration data by creatinine correction in the Third National Health and Nutrition Examination Survey (NHANES-III). Journal of Exposure Analysis and Environmental Epidemiology, 14(6), 457–465.
• Remer, T., Neubert, A., and Maser-Gluth, C. (2002). Anthropometry-based reference values for 24-h urinary creatinine excretion during growth and their use in endocrine and nutritional research. American Journal of Clinical Nutrition, 75(3), 561–569.
• StatCan (Statistics Canada) (2015). Instructions for Combining Multiple Cycles of Canadian Health Measures Survey (CHMS) Data. Ottawa, ON. Available upon request (infostats@canada.ca).

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