Longitudinal biomonitoring studies during preconception, pregnancy and early childhood are highly valuable tools for assessing environmental chemical exposures during sensitive windows and their effects on health and development. For the past 15 years, the Maternal-Infant Research on Environmental Chemicals (MIREC) Research Platform has been Canada's flagship study of the long-term effects of early life exposure to environmental chemicals. In light of the evolving scientific and legislative landscapes and need to address emerging research questions, MIREC Platform researchers at Health Canada consulted with scientific investigators of other cohort studies to inform the development of a future preconception or pregnancy longitudinal biomonitoring study. This effort included 1) hybrid consultation meetings on Dec 6, 2024 (Toronto, ON) and Jan 21, 2025 (Ottawa, ON) and 2) a virtual seminar series from October 2024 to June 2025 hosted by the Health Canada MIREC team. Our objective here is to share lessons learned from this consultation. We report on key lessons learned related to the themes of: 1) participant engagement, recruitment and retention, 2) validity and causal inference, and 3) study longevity. While the ultimate goal of this consultation was to inform future longitudinal biomonitoring studies in Canada, the content is largely generalizable and relevant to others planning, modifying, or evaluating observational research in reproductive and environmental epidemiology.

Human biomonitoring studies of per- and polyfluoroalkyl substances (PFAS) have typically focused on legacy PFAS. Data for alternative and precursor PFAS are emerging, but are still scarce. These data are critical for assessing exposure and human health risk. We measured serum concentrations of 40 PFAS among 2,775 premenopausal participants from the CARTaGENE cohort (Phase A: 2009–2010; Phase B: 2013–2014). We examined differences in geometric mean serum concentrations of PFAS with > 60

Human biomonitoring (HBM) provides an integrated chemical exposures assessment considering all routes and sources of exposure. The accurate interpretation and comparability of biomarkers of exposure and effect depend on harmonized, quality-assured sampling, processing, and analysis. Currently, the lack of broadly accepted guidance on minimum information required for collecting and reporting HBM data, hinders comparability between studies. Furthermore, it prevents HBM from reaching its full potential as a reliable approach for assessing and managing the risks of human exposure to chemicals.The European Chapter of the International Society of Exposure Science HBM Working Group (ISES Europe HBM working group) has established a global human biomonitoring community network (HBM Global Network) to develop a guidance to define the minimum information to be collected and reported in HBM, called the “Minimum Information Requirements for Human Biomonitoring (MIR-HBM)”. This work builds on previous efforts to harmonize HBM worldwide.The MIR-HBM guidance covers all phases of HBM from the design phase to the effective communication of results. By carefully defining MIR for all phases, researchers and health professionals can make their HBM studies and programs are robust, reproducible, and meaningful. Acceptance and implementation of MIR-HBM Guidelines in both the general population and occupational fields would improve the interpretability and regulatory utility of HBM data. While implementation challenges remain—such as varying local capacities, and ethical and legal differences at the national levels, this initiative represents an important step toward harmonizing HBM practice and supports an ongoing dialogue among policymakers, legal experts, and scientists to effectively address these challenges. Leveraging the data and insights from HBM, policymakers can develop more effective strategies to protect public health and ensure safer working environments.

OBJECTIVE:The Canadian Health Measures Survey (CHMS) employed two laboratory methods to measure each of bisphenol A (BPA) and triclosan in urine. This analysis compares method performance. METHODS:Method E-475 used GC-MS/MS to measure BPA in recruitment cycles 1-6 and triclosan in recruitment cycles 2-4. Method E-505 used UPLC-MS/MS for BPA and triclosan in biobanked samples from recruitment cycles 4-6. Using unweighted concentrations for samples available from both methods, and removing observations < LOD (BPA Cycles 4-6, n = 3114 and triclosan Cycle 4, n = 651), we compared E-475 and E-505 with descriptive statistics, scatterplots, and Bland Altman analysis. An E-475 variation using isotope dilution (ID) was performed for triclosan. After applying a model to correct E-475 triclosan for ID (E-475m), we compared modeled results to E-505. RESULTS:The geometric mean (GM) for BPA from E-475 vs. E-505 was 1.2 vs. 1.1 μg/L. The E-475/E-505 GM ratio was 1.03, and the lower-upper limits of agreements (LOA) were 0.59-1.81. The GM for triclosan from E-475 vs. E-505 was 31 vs. 20 μg/L. E-475 concentrations were 1.56 times E-505, and the LOAs were 0.87-2.78. The GM for triclosan from E-475m vs. E-505 was 19 vs. 20 μg/L. E-475m concentrations were 0.93 times E-505, and the LOAs were 0.53-1.64. CONCLUSIONS:BPA concentrations were comparable with E-475 and E-505. Triclosan concentrations were higher with E-475 than E-505. The E-475 triclosan concentrations became comparable to E-505 after correcting for ID. These results will have implications on whether BPA and triclosan data from the two methods can be combined and compared across CHMS recruitment cycles.

The FAIREHR (Findable, Accessible, Interoperable, Reusable Environmental and Health Registry) platform is a state-of-the-art online registry for prospective harmonization of human biomonitoring (HBM). It was developed by the HBM working group of the Europe Regional Chapter of the International Society of Exposure Science (ISES Europe) and is supported by the HBM Global Network. FAIREHR is designed to harmonize HBM metadata and support the implementation of the FAIR (Findable, Accessible, Interoperable and Reusable) Guiding Principles throughout HBM studies or programs. The registry enables preregistration of HBM by capturing key metadata on study design, metadata management, and planned methods before participant recruitment. This process enhances transparency and reproducibility in environmental and occupational health research. FAIREHR includes both study-level and program-level metadata. Its harmonized metadata template facilitates the storage of results (measurement data) in repositories such as IPCHEM and PEH. Here we outline the unique features of the FAIREHR platform, emphasizing its role in increasing research visibility, improving metadata comparability and harmonization, and strengthening the exchange of information. By supporting the effective use of HBM data, FAIREHR is expected to yield significant benefits for researchers, policymakers, and the broader fields of environmental and occupational health.

Neonicotinoids are a class of broad-spectrum insecticides used globally in agriculture for pest management. Due to their use in agriculture, horticulture and forestry, neonicotinoids have been found in food and water potentially resulting in human exposure. In this study, we developed and validated a new and sensitive method in ultra-high-performance liquid chromatography coupled with tandem mass spectrometry (UPLC-MSMS) using an atmospheric pressure chemical ionization (APCI) source to considerably reduce instrumental matrix effect when quantifying seven neonicotinoids in urine, namely acetamiprid (ACE), clothianidin (CLO), dinotefuran (DIN), imidacloprid (IMI), nitenpyram (NIT), thiacloprid (THIA) and thiamethoxam (THIAM), and five of their metabolites, specifically 4-hydroxy-imidacloprid (4-OHIM), 5-hydroxy-imidacloprid (5-OHIM), desmethylacetamiprid (DACE), desmethyl-clothianidin (DCLO) and desmethyl-thiamethoxam (DTHIAM). Sulfoxaflor (SULFO), a neonicotinoid replacement molecule was also included. Limits of detection were between 0.0050 and 0.025 mu g L-1. Instrumental matrix effect values were very low, between 80 and 443 %, 100 % being no signal suppression or increase (compare to between 12 and 50 % with an ESI source). This method was used to analyze 114 urine samples from cycle 6 of the Canadian Health Measures Survey (CHMS). The detection rates were 99.1 % for 5-OHIM, 96.5 % for 4-OHIM, 92.1 % for DACE, 91.2 % for DCLO, 90.4 % for CLO, 86.8 % for THIAM and 69.3 % for IMI. The remaining compounds had detection rates less than 40 %. Neonicotinoids with the highest geometric mean concentrations were CLO, DACE and 5-OHIM with 0.18, 0.16 and 0.15 mu g L-1, respectively.

Despite demonstrated disparities in environmental chemical exposures by racial identity, no Canadian study has systematically assessed the feasibility of using a nationally representative dataset to examine differences in chemical concentrations by race. We assessed the feasibility and constraints of analysing chemical exposures in racial populations, including visible minorities and populations of Indigenous identity, using biomonitoring data collected through the Canadian Health Measures Survey (CHMS). Our primary objectives were to assess the ability to 1) generate geometric means and percentiles of chemical concentrations for racial populations by age or sex, 2) statistically compare concentrations among racial populations, and 3) calculate time trends of concentrations by race. We conducted these analyses for several priority chemicals: lead, cadmium, benzene, bisphenol A (BPA), and di(2-ethylhexyl) phthalate (DEHP). Survey participants self-identified as one of the following: White, Black, East and Southeast Asian, South Asian, Middle Eastern, Latin American, First Nations, Metis, and Inuit. Analyses were conducted for individual and combined cycles of the CHMS. Using data from the latest CHMS cycle in which each chemical was measured, we observed that sample sizes were sufficient to report geometric mean concentrations for all races except Inuit. Due to privacy considerations associated with small sample sizes, the 5th and 95th percentile concentrations could not be consistently reported for all racial populations in this analysis. While we were able to statistically compare concentrations among racial populations, the analysis was constrained by the limited number of statistical degrees of freedom available in a single CHMS cycle. Both of these constraints were alleviated by combining multiple cycles of data. The analysis of time trends was less subject to privacy and statistical limitations; we were able to calculate time trends of chemical concentrations for all racial populations. Our findings provide an important baseline for follow-up investigations of descriptive and etiological analyses of environmental chemical exposures and race in the CHMS.

Exposure load (EL) is an indicator of multiple chemical exposures based on human biomonitoring data. We used EL methodology and human biomonitoring health-based guidance values (HB2GVs) as exposure thresholds to create a new metric called Cumulative Health Risk from Exposure Load (CHREL). HB2GVs are derived by calculating the concentration of a biomarker consistent with a health protective exposure guidance value. CHREL analysis was conducted using Canadian Health Measures Survey (CHMS) cycle 3 and 4 biomonitoring data. Based on 18 chemicals, more than half of the Canadian population had an estimated CHRELTOTAL TOTAL of 1 or more, indicative of chemical exposures potentially above selected exposure guidance values. Females had a significantly lower CHRELTOTAL TOTAL compared to males, 12-19 year olds had a lower CHRELTOTAL TOTAL compared to older age groups (significant compared to 40-59 year olds), and nonsmokers had a significantly lower CHRELTOTAL TOTAL than smokers. Small segments of the population had a CHRELLIVER LIVER or a CHRELNERV NERV of 1 or more, indicating exposures potentially above guideline levels for chemicals affecting the liver or nervous system. CHRELCANC CANC was calculated based on 6 chemicals with HB2GVs derived for cancer endpoints. At the 10-5-5 risk level, most people had an estimated CHRELCANC CANC of 3, indicative of multiple chemicals that may exceed negligible cancer risk. The most important contributors to exposures above HB2GVs were inorganic arsenic, mercury, acrylamide, xylenes, benzene and triclosan. Keeping certain assumptions, uncertainties and limitations in mind, the CHREL indicator can be used to obtain a picture of potential cumulative health risks from combined chemical exposures in a population, and as a comparative measure between subpopulations, including vulnerable subgroups.

BACKGROUND:Whilst single chemical exposures are suspected to be obesogenic, the combined role of chemical mixtures in paediatric obesity is not well understood. OBJECTIVES:We aimed to evaluate the potential associations between chemical mixtures and obesity in a population-based sample of Canadian children. METHODS:We ascertained biomonitoring and health data for children aged 3-11 from the cross-sectional Canadian Health Measures Survey from 2007 to 2019. Several chemicals of interest were measured in blood or urine and paediatric obesity was defined based on measured anthropometrics. Using quantile-based G computational analysis, we quantified the effects of three chemical mixtures selected a priori. Models were adjusted for sociodemographic and environmental factors identified through a directed acyclic graph. Results are presented through adjusted relative risks (RR) with 95% confidence intervals (95% CI). RESULTS:We included 9147 children. Of these, 24.1% were overweight or obese. Exposure to the mixture of bisphenol A, acrylamide, glycidamide, metals, parabens and arsenic increased the risk of childhood overweight or obesity by 45% (95% CI 1.09, 1.93), obesity by 109% (95% CI 1.27, 3.42) and central obesity by 82% (95% CI 1.30, 2.56). CONCLUSIONS:Our findings support the role of early childhood chemical exposures in paediatric obesity and the potential combined effects of chemicals.

In 2022, the International Society of Exposure Science (ISES) International Human Biomonitoring (i-HBM) Working Group launched a free, online repository of biomonitoring guidance values referred to as the Human Biomonitoring Health-Based Guidance Value (HB2GV) Dashboard. The goal of the Dashboard is to assist global human biomonitoring data users (e.g., risk assessors, risk managers) and human biomonitoring programs with a readily available compilation of guidance values for the general population. The Dashboard contains approximately 600 HB2GVs for over 150 chemicals or their metabolites. Although there are many different types of HB2GVs, most are Biomonitoring Equivalents (BEs), Human Biomonitoring (HBM-I and HBM-II) values, or Human Biomonitoring Guidance Values (HBM-GVs). For users new to human biomonitoring, understanding how the different types of HB2GVs are derived and how to interpret those values in the context of human biomonitoring data can be difficult. Therefore, there is a need to inform users of the differences among available guidance values and to help users identify the HB2GV that could be most suitable for their purposes. Here, we summarize the derivation of HB2GVs for a case study chemical, di-(2-ethylhexyl) phthalate (DEHP). We selected DEHP as there are 36 unique HB2GVs available from three of the most common types of guidance values (i.e., BE, HBM-I value, HBM-GV). We also compare the available HB2GVs with a focus on the differences among their derivation methods, relative quality and confidence, and interpretation. This case study provides guidance on the use of existing HB2GVs for health-based interpretation of human biomonitoring data that may be applied to other chemicals. As with any other type of guidance or regulatory value (e.g., RfDs, MRLs), thoughtful selection and use are strongly encouraged. Appropriately interpreting HBM data with the aid of guidance values can result in improved decision making which, ultimately, could lead to better protection of public health.

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

Bisphenol A (BPA) is a synthetic chemical used for the manufacturing of plastics, epoxy resin, and many personal care products. This ubiquitous endocrine disruptor is detectable in the urine of over 80% of North Americans. Although adverse neurodevelopmental outcomes have been observed in children with high gestational exposure to BPA, the effects of prenatal BPA on brain structure remain unclear. Here, using magnetic resonance imaging (MRI), we studied the associations of maternal BPA exposure with children's brain structure, as well as the impact of comparable BPA levels in a mouse model. Our human data showed that most maternal BPA exposure effects on brain volumes were small, with the largest effects observed in the opercular region of the inferior frontal gyrus (ρ = -0.2754), superior occipital gyrus (ρ = -0.2556), and postcentral gyrus (ρ = 0.2384). In mice, gestational exposure to an equivalent level of BPA (2.25 μg BPA/kg bw/day) induced structural alterations in brain regions including the superior olivary complex (SOC) and bed nucleus of stria terminalis (BNST) with larger effect sizes (1.07≤ Cohens d ≤ 1.53). Human (n = 87) and rodent (n = 8 each group) sample sizes, while small, are considered adequate to perform the primary endpoint analysis. Combined, these human and mouse data suggest that gestational exposure to low levels of BPA may have some impacts on the developing brain at the resolution of MRI.

BACKGROUND AND AIM: Pediatric obesity rates in Canada have nearly tripled in the last 30 years, leading to increased rates of morbidity. While environmental exposures are suspected to be obesogenic, data are lacking and mostly employ a single-exposure approach. We aimed to evaluate the potential associations between multiple environmental factors and pediatric obesity. METHODS: We used nationally-representative biomonitoring and health data for children aged 3-11 from the cross-sectional Canadian Health Measures Survey. Chemicals of interest, monitored in blood or urine, were polyaromatic hydrocarbons (PAH), bisphenol A (BPA), parabens, perfluorinated compounds, phthalates and metals. Obesity was characterized by WHO sex-specific body mass index (BMI) for age z-scores. Central obesity was defined using international waist circumference percentile cutoffs. Using generalized additive models, we examined the impact of multiple environmental characteristics, including proximity to greenspace, fine particulate matter (PM 2.5), nighttime light brightness and walkability (active living environment), on associations between single-chemical exposures and obesity. Using quantile-based G computational analysis, we quantified the combined effects of chemicals captured in all cycles, where feasible. Models were adjusted for confounders identified in a directed acyclic graph. Results are adjusted odd ratios with 95% confidence intervals (95% CI). RESULTS: Overall, 9,147 children were included. In single-exposure models, several PAH compounds, BPA, cadmium and total phthalates were linked to increased obesity and central obesity. Per interquartile range increase in total PAHs, risks of obesity and central obesity were elevated to 1.09 (95%CI 1.01, 1.18) and 1.14 (95%CI 1.01, 1.30), respectively. In combined-effects models for PAHs and BPA, risks of obesity and central obesity were strengthened to 1.46 (95%CI 1.20, 1.78) and 1.29 (95%CI 1.10, 1.56), respectively. CONCLUSIONS: Our findings support the role of early chemical exposure in pediatric obesity, particularly PAHs. The combined effects of chemicals strengthened the observed associations. KEYWORDS: Pediatric; Chemicals; Obesity; Public Health; Environment

People are often concurrently exposed to numerous chemicals. Here we sought to leverage existing large biomonitoring datasets to improve our understanding of multi-chemical exposures in a population. Using nationallyrepresentative data from the 2012?2015 Canadian Health Measures Survey (CHMS), we developed Exposure Load, a metric that counts the number of chemicals measured in people above a defined concentration threshold. We calculated Exposure Loads based on five concentration thresholds: the analytical limit of detection (LOD) and the 50th, 75th, 90th and 95th percentiles. Our analysis considered 44 analyte biomarkers representing 26 chemicals from the 2012?2015 CHMS; complete biomarker data were available for 1858 participants aged 12?79 years following multiple imputation of results that were missing due to sample loss. Chemicals may have one or more biomarkers, and for the purposes of Exposure Load calculation, participants were considered to be exposed to a chemical if at least one biomarker was above the threshold. Distributions of Exposure Loads are reported for the total population, as well as by age group, sex and smoking status. Canadians had an Exposure Load between 9 and 21 (out of 26) when considering LOD as the threshold, with the majority between 13 and 18. At higher thresholds, such as the 95th percentile, the majority of Canadians had an Exposure Load between 0 and 3, although some people had an Exposure Load of up to 15, indicating high exposures to multiple chemicals. Adolescents aged 12?19 years had significantly lower Exposure Loads than adults aged 40?79 years at all thresholds and adults aged 20?39 years at the 50th and 75th percentiles. Smokers had significantly higher Exposure Loads than nonsmokers at all thresholds except the LOD, which was expected given that tobacco smoke is a known source of certain chemicals included in our analysis. No differences in Exposure Loads were observed between males and females at any threshold. These findings broadly suggest that Canadians are concurrently exposed to many chemicals at lower concentrations and to fewer chemicals at high concentrations. They should assist in identifying vulnerable subpopulations disproportionately exposed to numerous chemicals at high concentrations. Future work will use Exposure Loads to identify prevalent chemical combinations and their link with adverse health outcomes in the Canadian population. The Exposure Load concept can be applied to other large datasets, through collaborative efforts in human biomonitoring networks, in order to further improve our understanding of multiple chemical exposures in different populations.

BACKGROUND:Parabens are chemical substances used as preservatives for their antibacterial and antifungal properties in many personal care products, and sometimes in pharmaceutical and food products. Concerns for adverse human health effects arise from animal studies showing endocrine disrupting effects, such as changes in the timing of puberty and alterations in reproductive hormone activity. Our objective was to examine the association between urinary concentrations of parabens and serum concentrations of estradiol, progesterone, follicle stimulating hormone [FSH], and luteinizing hormone [LH]) in girls from the general population.METHODS:We conducted a cross-sectional study in girls ages 6-17 years, using data from the Canadian Health Measures Survey (2014-2015). The association between concentrations of creatinine-standardized urinary parabens and serum hormone concentrations was analyzed with multivariable linear regressions, adjusting for potential confounders (i.e., age, body mass index, ethnicity, household income, sampling season; prenatal exposure to cigarette smoke for girls 6-11 years).RESULTS:The 382 girls and teens included in the study had a mean age of 11.0 years; 76% were white and 73% had a body mass index in the range normal/underweight. Most participants (92%) had least one paraben detected in their urine. Girls with higher urinary paraben concentrations had significantly lower serum concentrations of estradiol, LH, and FSH, but not of progesterone. A doubling in the sum of urinary parabens was associated with 5.8% lower estradiol (95% CI -9.3, -2.1), 4.2% lower FSH (95% CI -7.9, -0.3), and 10.8% lower LH (95% CI -17.4, -3.7). The analysis of individual compounds showed that all four parabens were similarly associated with lower concentrations of estradiol, FSH, and LH. We further analyzed younger girls (6-11 years) and found that urinary parabens were similarly associated with lower estradiol and LH (doubling in the sum of parabens associated with 5.9% lower estradiol [95% CI -10.5, -1.0] and 10.9% lower LH [95% CI -20.2, -0.6]). In this younger subgroup, the association estimate for FSH, however, was attenuated and no longer statistically significant.DISCUSSION:We observed that exposure to parabens was associated with reduced concentrations of circulating reproductive hormones, suggesting that these chemicals could alter the development and function of the endocrine system in girls. Further prospective research using long-term assessment of parabens exposure and of reproductive development may better determine endocrine disrupting effects of parabens.