Douglas Haines

Biomonitoring of phthalate metabolites in the Canadian population through the Canadian Health Measures Survey (2007-2009).

Human exposure to phthalates occurs through multiple sources and pathways. In the Canadian Health Measures Survey 2007-2009, 11 phthalate metabolites, namely, MMP, MEP, MnBP, MBzP, MCHP, MCPP, MEHP, MEOHP, MEHHP, MnOP, and MiNP were measured in urine samples of 6-49 year old survey respondents (n=3236). The phthalate metabolites biomonitoring data from this nationally-representative Canadian survey are presented here. The metabolites MEP, MnBP, MBzP, MCPP, MEHP, MEOHP and MEHHP were detected in >90% of Canadians while MMP, MCHP, MnOP and MiNP were detected in <20% of the Canadian population. Step-wise regression analyses were carried out to identify important predictors of volumetric concentrations (μg/L) of the metabolites in the general population. Individual multiple regression models with covariates age, sex, creatinine, fasting status, and the interaction terms age×creatinine, age×sex and fasting status×creatinine were constructed for MEP, MnBP, MBzP, MCPP, MEHP, MEOHP and MEHHP. The least square geometric mean (LSGM) estimates for volumetric concentration (μg/L) of the metabolites derived from respective regression models were used to assess the patterns in the metabolite concentrations among population sub-groups. The results indicate that children had significantly higher urinary concentrations of MnBP, MBzP, MEHP, MEHHP, MEOHP and MCPP than adolescents and adults. Moreover, MEP, MBzP, MnBP and MEOHP concentrations in females were significantly higher than in males. We observed that fasting status significantly affects the concentrations of MEHP, MEHHP, MEOHP, and MCPP metabolites analyzed in this study. Moreover, our results indicate that the sampling time could affect the DEHP metabolite concentrations in the general Canadian population.

Do perfluoroalkyl substances affect metabolic function and plasma lipids?--Analysis of the 2007-2009, Canadian Health Measures Survey (CHMS) Cycle 1.

BACKGROUND Perfluorinated compounds (PFCs) are man-made chemicals that are heat stable, non-flammable and able to repel both water and oils. Biomonitoring research shows global distribution in human, animal and aquatic environments of these chemicals. PFCs have been shown to activate the peroxisome proliferator-activated receptors which play a large role in metabolism and the regulation of energy homeostasis. Previous epidemiological research has also suggested a potential role of PFCs on lipid and glucose metabolism. OBJECTIVES The objectives of this study were to examine the association between the levels of perfluorinated compounds perfluorooctane sulfonate (PFOS), perfluorooctanoic acid (PFOA), and perfluorohexane sulfonate (PFHxS) in plasma and metabolic function and plasma lipid levels. METHODS Using cross-sectional data from the Canadian Health Measures Survey (Cycle 1 2007-2009) we examined the association in adults between plasma levels of PFOA, PFOS and PFHxS (n=2700) on cholesterol outcomes, metabolic syndrome and glucose homeostasis using multivariate linear and logistic regression models. RESULTS We found some evidence of a significant association between perfluoroalkyl substances, notably PFHxS, with total cholesterol (TC), low-density lipoprotein cholesterol (LDL), total cholesterol/high density lipoprotein cholesterol ratio (TC/HDL) and non-HDL cholesterol as well as an elevated odds of high cholesterol. We found some associations with PFOA and PFOS in our unweighted models but these results did not remain significant after weighting for sampling strategy. We found no association with metabolic syndrome, or glucose homeostasis parameters. CONCLUSIONS This study showed lower levels of PFOA and PFOS and slightly higher levels of PFHxS than other published population studies. Our results did not give significant evidence to support the association with cholesterol outcomes with PFOS and PFOA. However, we did observe several significant associations with the PFHxS and cholesterol outcomes (LDL, TC, NON-HDL, TC/HDL ratio).

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

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

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

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

An overview of human biomonitoring of environmental chemicals in the Canadian Health Measures Survey: 2007-2019.

Human biomonitoring (HBM) is used to indicate and quantify exposure by measuring environmental chemicals, their metabolites or reaction products in biological specimens. The biomonitoring component of the Canadian Health Measures Survey (CHMS) is the most comprehensive initiative providing general population HBM data in Canada. The CHMS is an ongoing cross-sectional direct measures survey implemented in 2-year cycles. It provides nationally-representative data on health, nutritional status, environmental exposures, and related risks and protective characteristics. The survey follows a robust planning, design and sampling protocol as well as a comprehensive quality assurance and quality control regime implemented for all aspect of the survey to ensure the validity of the HBM results. HBM blood and urine data are available for CHMS cycles 1 (2007-2009), 2 (2009-2011) and 3 (2012-2013). Field collection has been completed for cycle 4 (2014-2015), with cycle 5 (2016-2017) in progress and cycle 6 planning (2018-2019) being finalized. Biomonitoring results for 279 chemicals are expected over the six cycles of the CHMS (220 in individual blood, urine or hair samples, and 59 in pooled serum samples). The chemicals include metals and trace elements, polychlorinated biphenyls (PCBs), organochlorines, flame retardants, perfluoroalkyl substances, volatile organic compounds (VOCs) and metabolites, environmental phenols, triclocarban, acrylamide, pesticides (e.g., triazines, carbamates, organophosphates, phenoxy, pyrethroids) and/or their metabolites, chlorophenols, polycyclic aromatic hydrocarbon (PAH) metabolites, phthalates and alternate plasticizer metabolites, and tobacco biomarkers. Approximately one half of the chemicals measured in individual blood and urine samples over the first three cycles were detected in more than 60% of samples. CHMS biomonitoring data have been used to establish baseline HBM concentrations in Canadians; inform public health, regulatory risk assessment and management decisions; and fulfil national and international reporting requirements. Concurrent efforts are underway in Canada to develop statistically- and risk-based concepts and tools to interpret biomonitoring data.

Human biomonitoring reference values for metals and trace elements in blood and urine derived from the Canadian Health Measures Survey 2007–2013

Human biomonitoring reference values are statistical estimates that indicate the upper margin of background exposure to a given chemical at a given time. Nationally representative human biomonitoring data on 176 chemicals, including several metals and trace elements, are available in Canada from 2007 to 2013 through the Canadian Health Measures Survey (CHMS). In this work, we used a systematic approach based on the reference interval concept proposed by the International Federation of Clinical Chemistry and Laboratory Medicine and the International Union of Pure and Applied Chemistry to derive reference values (RV95s) for metals and trace elements. These RV95s were derived for blood and urine matrices in the general Canadian population based on the latest biomonitoring data from the CHMS. Biomarkers were chosen based on specific selection criteria, including widespread detection in Canadians (≥66% detection rate). Reference populations were created for each biomarker by applying appropriate exclusion criteria. Age and sex were evaluated as possible partitioning criteria and separate RV95s were derived for the sub-populations in cases where partitioning was deemed necessary. The RV95s for metals and trace elements in blood ranged from 0.18μg/L for cadmium in young children aged 3-5 years to 7900μg/L for zinc in males aged 20-79 years. In the case of urinary biomarkers, the RV95s ranged from 0.17μg/L for antimony in the total population aged 3-79 years to 1400mg/L for fluoride in adults aged 20-79 years. These RV95s represent the first set of reference values for metals and trace elements in the general Canadian population. We compare the RV95s from other countries where available and discuss factors that could influence such comparisons.

Human biomonitoring reference values for some non-persistent chemicals in blood and urine derived from the Canadian Health Measures Survey 2009-2013

The Canadian Health Measures Survey collects nationally representative human biomonitoring data on a suite of chemicals and their metabolites, including many non-persistent chemicals. Data has been collected on non-persistent chemicals, including acrylamide, chlorophenols, environmental phenols and triclocarban, organophosphate insecticides, phthalates, polycyclic aromatic hydrocarbon, pyrethroid insecticides, and volatile organic compounds from 2009 to 2013. Using a systematic approach building on the reference interval concept proposed by the International Federation of Clinical Chemistry and Laboratory Medicine and the International Union of Pure and Applied Chemistry, we derive human biomonitoring reference values (RV95s) for these classes of non-persistent chemicals in blood and urine for the general Canadian population. RV95s were derived for biomarkers of non-persistent chemicals with widespread detection in Canadians (>66% detection rate). Samples with urinary creatinine levels outside the recommended range of 0.3-3.0 μg/L were excluded. Reference populations were constructed by applying smoking and fasting as exclusion criteria where appropriate. Age and sex were evaluated as possible partitioning criteria and separate RV95s were derived for sub-populations in cases where partitioning was deemed necessary. Reference values were derived for 40 biomarkers and represent the first set of RV95s for non-persistent chemicals in the general Canadian population. These values provide a measure of the upper margin of background exposure in the general population and can be compared against individual and population human biomonitoring data. RV95s can be used to by public health officials to identify individuals with high exposures, and by risk assessors and risk managers to identify atypical exposures or subpopulations with elevated exposures.

International conference on human biomonitoring, Berlin 2010

This focus issue assembles publications on the issues presented and discussed at the two-day international conference “Human Biomonitoring: Political benefits – scientific challenges” held in Berlin on September 26–28, 2010. The major aim of this conference was to bring together the broad variety of human biomonitoring (HBM) activities conducted worldwide to present a clear picture of HBMs use in science and regulation. The conference was jointly organized by the German Federal Ministry for the Environment, Nature Conservation and Nuclear Safety (BMU) and the German Federal Environment Agency (UBA) to elucidate and describe the scientific challenges as well as the political benefits of HBM. The global dimension of HBM was illustrated by contributions from HBM activities in Asia, Africa, North and South America, and Europe, and the participation of experts from 36 countries. HBM studies investigate human exposure to environmental chemicals and their potentially harmful impacts on public health. HBM informs environment and health policy by providing scientific data on: (a) which substances are absorbed by the human body, (b) the exposure levels, (c) whether certain groups of the population are particularly affected, and (d) whether chemical policy regulations have led to the intended decrease in exposure. Based on these assumptions the conference participants were invited to: examine the strengths and limitations of HBM in the detection and assessment of human exposures, take a critical look at which substances should be examined as a matter of priority and the health impacts that may be expected from chemical exposure, and discuss the incorporation of HBM into national and international initiatives on environmental health. The conference opened with a discussion by a panel of stake-holders on the strengths and limitations of HBM. The scientific conference agenda consisted of five sessions: (1) lessons learned from existing programs; (2) future challenges and emerging programs; (3) HBM and health effects; (4) risk assessment of HBM data; and (5) going global – Do we need global HBM? The conference concluded with a panel discussion on the political dimension of HBM. Expert speakers from nearly all parts of the world confirmed, with their extensive studies, that HBM is a useful tool for detecting human exposure to industrial chemicals, as well as to natural substances. The conference demonstrated the significant growth in knowledge of environmental chemical exposure in humans and the related health impacts. This growing knowledge requires scientists and regulators from all over the world to address public concerns and to take appropriate actions. Chemical priorities for HBM vary from country-to-country and region-to-region due to differences in current chemical usage, exposure levels and regulation status. For example, in Europe the focus has changed from substances such as lead and cadmium to second- and third-generation plasticizers and flame retardants. In Asia and Africa, the emphasis is currently on substances including dichlorodiphenyltrichloroethane (DDT), polychlorinated biphenyls (PCBs) and lead, many of which have long been banned or are subject to severe use restrictions in Europe, North America and elsewhere. Thus, HBM data show that some products remain in use in certain countries despite having been banned in others. Some of these substances may be present due to their persistence in the environment and global distribution. As new substances are constantly being introduced, there is a need to expand the range of substances that can be measured by HBM to keep pace with chemical product innovation. Development of new analytical methods for emerging substances and their inclusion in future HBM studies is one of the challenges ahead. Establishing specimen biobanks will provide a useful resource for future reference and analyses. Todays substances might be tomorrows challenges. The HBM conference illustrated the need to promote harmonized criteria, procedures and tools for the interpretation of HBM data and the enhancement of their use in human health risk assessment. Toxicological information required for developing these tools is becoming increasingly available through regulatory requirements such as those under the Registration, Evaluation, Authorization and Restriction of Chemicals (REACH) regulation and similar initiatives in other countries. HBM provides scientific data to inform decision making by regulators, policy makers, and the general public. On the regulatory and policy side, HBM provides a mechanism for monitoring the success of policies in reducing exposure to environmental chemicals and for identifying areas for priority action. Approaches for communicating HBM results to the various users require further improvement. BMU and UBA, the organizers of the HBM conference, sincerely thank all authors and conference participants for their valuable contributions. We also want to gratefully recognize the work of the scientific committee for putting together an interesting programme and ensuring the high quality of the conference and the importance of its outcomes. Special thanks are due to the following additional members of the scientific committee: Marika Berglund, Karolinska Institutet, Sweden; Argelia Castano, Instituto de Salud Carlos III, Spain; Birger Heinzow, State Office for Social Services, Germany; Holger Koch, Institute for Prevention and Occupational, Medicine, Germany; Greet Schoeters, Flemish Institute for Technological Research, Belgium; Yasuyuki Shibata, National Institute for Environmental Studies, Japan; and Ann-Catherine Viso, Institut de Veille Sanitaire, France.

Chapter 2D:Examples of Ongoing International Surveys: Canada

In the vast geographic and diverse socio-demographic Canadian context, a multipronged strategy to obtain adequate human biomonitoring coverage is necessary. Although there have been several previous Canadian human biomonitoring activities, this chapter describes four major current biomonitoring initiatives: 1) the nationally representative Canadian Health Measures Survey (CHMS), 2) the Canada-wide Maternal–Infant Research on Environmental Chemicals (MIREC) study, 3) the research and community-based Northern Contaminants Program (NCP), and 4) mercury biomonitoring of First Nations people living on reserves south of the 60th parallel. While distinct approaches are required depending on the target population, taken together these initiatives provide a reasonable overview of current exposures to environmental chemicals and contribute to the development of policies and programs to protect the health of Canadians.