Biomarkers of poly- and perfluoroalkyl substances (PFAS) in Sub-Arctic and Arctic communities in Canada.

Polyfluoroalkyl substances and perfluoroalkyl substances (PFAS) are a family of anthropogenic chemicals that are used in food packaging, waterproof clothing, and firefighting foams for their water and oil resistant properties. Though levels of some PFAS appear to be decreasing in Canada's south, environmental levels have been increasing in the Arctic due to long-range transport. However, the implications of this on human exposures in sub-Arctic and Arctic populations in Canada have yet to be established. To address this data gap, human biomonitoring research was completed in Old Crow, Yukon, and the Dehcho region, Northwest Territories. Blood samples were collected from adults residing in seven northern First Nations and were analyzed by liquid chromatography mass spectrometry. A total of nine PFAS were quantified: perfluorooctanoic acid (PFOA), perfluorooctane sulphonic acid (PFOS), perfluorohexane sulphonic acid (PFHxS), perfluorononanoic acid (PFNA), perfluorodecanoic acid (PFDA), and perfluoroundecanoic acid (PFUdA), perfluorobutanoic acid (PFBA), perfluorohexanoic acid (PFHxA), and perfluorobutane sulphonic acid (PFBS). In the Dehcho (n = 124), five PFAS had a detection rate greater than 50% including PFOS, PFOA, PFHxS, PFNA, and PFDA. In addition to these PFAS, PFUdA was also detected in at least half of the samples collected in Old Crow (n = 54). Generally, male participants had higher concentrations of PFAS compared to female participants, and PFAS concentrations tended to increase with age. For most PFAS, Old Crow and Dehcho levels were similar or lower to those measured in the general Canadian population (as measured through the Canadian Health Measures Survey or CHMS) and other First Nations populations in Canada (as measured through the First Nations Biomonitoring Initiative or FNBI). The key exception to this was for PFNA which, relative to the CHMS (0.51 µg/L), was approximately 1.8 times higher in Old Crow (0.94 µg/L) and 2.8 times higher in Dehcho (1.42 µg/L) than observed in the general Canadian population. This project provides baseline PFAS levels for participating communities, improving understanding of human exposures to PFAS in Canada. Future research should investigate site-specific PFNA exposure sources and monitor temporal trends in these regions.

Exposure of the French population to bisphenols, phthalates, parabens, glycol ethers, brominated flame retardants, and perfluorinated compounds in 2014-2016: Results from the Esteban study.

BACKGROUND: As part of the French Human Biomonitoring (HBM) programme, the Esteban study described, among other things, biomarkers levels of various chemicals in adults (18-74 years old) and children (6-17 years old). This paper describes the design of the study and provides, for the first time, data on the biological exposure of the general French population to a wide range of contaminants posing a threat to human health which are currently found in domestic environments. METHODS: Esteban is a cross-sectional study conducted on a nationwide sample of the French general population. Exposure biomarkers of six families of contaminants deemed detrimental to adults' and children's health were measured in biological samples collected either at participants' homes by a nurse, or brought to a National Health Insurance examination centre. All participants were randomly selected (2503 adults and 1104 children). The geometric mean and percentiles of the distribution of levels were estimated for each biomarker. Most of the descriptive statistical analyses were performed taking into account the sampling design. RESULTS: Results provided a nationwide description of biomarker levels. Bisphenols (A, S and F), and some metabolites of phthalates and perfluorinated compounds (PFCs) (specifically, PFOS and PFOA) were quantified in almost all the biological samples analysed. Higher levels were observed in children (except for PFCs). Levels were coherent with international studies, except for bisphenols S and F, brominated flame retardants (BFRs) and parabens (with higher levels reported in the USA than in France). CONCLUSION AND PERSPECTIVES: This study is the first to provide a representative assessment of biological exposure to domestic contaminants at the French population level. Our results show that the French general population was exposed to a wide variety of pollutants in 2014-2016, and identify the determinants of exposure. These findings will be useful to stakeholders who wish to advocate an overall reduction in the French population's exposure to harmful substances. Similar future studies in France will help to measure temporal trends, and enable public policies focused on the reduction of those chemicals in the environment to be evaluated.

WITHDRAWN: Corrigendum to "Biomarkers of cadmium, lead and mercury exposure in relation with early biomarkers of renal dysfunction and diabetes: Results from a pilot study among aging Canadian" [Toxicol. Lett. 312 (2019) 148-156].

The Publisher regrets that this article is an accidental duplication of an article that has already been published, https://doi.org/10.1016/j.toxlet.2019.05.020. The duplicate article has therefore been withdrawn. The full Elsevier Policy on Article Withdrawal can be found at https://www.elsevier.com/about/our-business/policies/article-withdrawal.

Biomarkers of cadmium, lead and mercury exposure in relation with early biomarkers of renal dysfunction and diabetes: Results from a pilot study among aging Canadians.

Cadmium (Cd), lead (Pb) and mercury (Hg) are known nephrotoxicants that have been associated with the risk of developing type-2 diabetes (T2D). The aim of this pilot study was to explore relations between biomarkers of Cd, Pb and Hg exposure, early urinary biomarkers of renal dysfunction (kidney-injured molecule-1 (KIM-1), N-acetylglucosaminidase and retinol-binding protein (RBP)) and plasma biomarkers deemed predictive of the risk of developing T2D (adiponectin, leptin, branched-chain and aromatic amino acids), among 70 participants (age range: (46-87 yrs)) from the Canadian Longitudinal Study on Aging (CLSA) with normal glycemic control (glycated haemoglobin ≤ 6.5%) in all but four of them. Significant (p < 0.05) Spearman correlation coefficients were obtained between: plasma adiponectin and RBP (r = 0.42), urinary Cd (r = 0.32), blood Cd (r = 0.36); KIM-1 and CdU (r = 0.33) as well as HgU (r = 0.37); RBP and isoleucine (r = -0.28), leucine (r = -0.33), tyrosine (r = -0.3) and valine (r = -0.44); CdU and isoleucine and valine (r = -0.27 for both). Multiple linear regression analyses showed that some T2D-related biomarkers are confounders of associations between RBP and Hg or Cd biomarkers. Path analyses support a mediating effect of adiponectin on the relation between urinary Cd and RBP. Concluding, this pilot study originally investigated a comprehensive set of biomarkers on complex interactions between toxic metal exposure, renal function and T2D in a group of aging Canadians. Its findings warrant further investigation of longitudinal data in a greater number of participants.

Organochlorine Levels in Plasma and Risk of Multiple Myeloma.

OBJECTIVE: The aim of this study was to estimate the association between organochlorine pesticides and polychlorinated biphenyls (PCBs) and multiple myeloma (MM). METHODS: The risk of MM from organochlorine compounds was examined in a population-based case-control study in British Columbia, Canada. Congeners of PCBs and pesticides or pesticide metabolites were measured in plasma of 325 cases and 327 controls. RESULTS: Most organochlorine analytes showed a significant association with MM. The strongest association (highest vs lowest quartile) was oxychlordane (odds ratio = 7.44; 95% confidence interval = 4.19 to 13.21). No heterogeneity was detected between organochlorines levels and MM subtypes. Only oxychlordane and ß-hexachlorocyclohexane (ß-HCCH) were identified as significant independent predictors of MM. CONCLUSION: Our study provides evidence that organochlorines contribute to the risk of MM.

Arsenic levels among pregnant women and newborns in Canada: Results from the Maternal-Infant Research on Environmental Chemicals (MIREC) cohort.

Arsenic is a common environmental contaminant from both naturally-occurring and anthropomorphic sources and human exposure can be detected in various tissues. Its toxicity depends on many factors including the chemical form, valence state, bioavailability, metabolism and detoxification within the human body. Of paramount concern, particularly with respect to health effects in children, is the timing of exposure as the prenatal and early life periods are more susceptible to toxic effects. The Maternal-Infant Research on Environmental Chemicals (MIREC) cohort was established to obtain national-level biomonitoring data for approximately 2,000 pregnant women and their infants between 2008 and 2011 from 10 Canadian cities. We measured total arsenic (As) in 1st and 3rd trimester maternal blood, umbilical cord blood, and infant meconium and speciated arsenic in 1st trimester maternal urine. Most pregnant women had detectable levels of total arsenic in blood (92.5% and 87.3%, respectively, for 1st and 3rd trimester); median difference between 1st and 3rd trimester was 0.1124µg/L (p<0.0001), but paired samples were moderately correlated (Spearman r=0.41, p<0.0001). Most samples were below the LOD for umbilical cord blood (50.9%) and meconium (93.9%). In 1st trimester urine samples, a high percentage (>50%) of arsenic species (arsenous acid (As-III), arsenic acid (As-V), monomethylarsonic acid (MMA), and arsenobetaine (AsB)) were also below the limit of detection, except dimethylarsinic acid (DMA). DMA (>85% detected) ranged from

Determinants of urinary concentrations of dialkyl phosphates among pregnant women in Canada - Results from the MIREC study.

Organophosphate (OP) insecticides are commonly used in agriculture. Their use decreased in recent years as they were gradually replaced by other pesticides, but some OPs are still among the insecticides most used in Canada. Exposure to elevated levels of OPs during pregnancy has been associated with adverse birth outcomes and poorer neurodevelopment in children. The objective of the present study was to examine the relationship between the concentrations of OP pesticides urinary dialkyl phosphate (DAP) metabolites and various factors that are potential sources of exposure or determinants of DAP levels. In the Maternal-Infant Research on Environmental Chemicals (MIREC) Study, six DAPs were measured in 1st trimester urine samples of 1884 pregnant women living in Canada. They were grouped into sums of dimethyl alkyl phosphates (DMAP) and diethyl alkyl phosphates (DEAP) for statistical analysis. We found that 93% of women had at least one DAP detected in their urine. Geometric means (GM) of specific gravity-corrected levels for urine dilution were 59 (95% CI 56-62) and 21 (95% CI 20-22) nmol/L for DMAP and DEAP, respectively. The following characteristics were significantly associated with higher urinary concentrations of DMAP or DEAP: higher education, nulliparous, normal pre-pregnancy body mass index, non-smoker, not fasting at sampling, winter season at sampling, and early and late day collection times. Dietary items that were significantly related with higher urinary concentrations included higher intake of citrus fruits, apple juice, sweet peppers, tomatoes, beans and dry peas, soy and rice beverages, whole grain bread, white wine and green and herbal teas. This study indicates that exposure to these compounds is quasi-ubiquitous. The factors associated with greater DAP levels identified here could be useful to regulatory agencies for risk analysis and management. However, some exposure misclassification might occur due to the single DAP measurement available, and to the presence of preformed DAPs in the environment.

Concentrations of persistent organic pollutants in maternal and cord blood from the maternal-infant research on environmental chemicals (MIREC) cohort study.

BACKGROUND: Pregnant women are an especially important population to monitor for environmental exposures given the vulnerability of the developing fetus. During pregnancy and lactation chemical body burdens may change due to the significant physiological changes that occur. Developmental exposures to some persistent organic pollutants (POPs) have been linked with adverse health outcomes. METHODS: First trimester maternal and cord blood plasma concentrations of several POPs including polychlorinated biphenyls (PCBs), organochlorine pesticides (OCs), polybrominated diphenyl ethers (PBDE)s and perfluoroalkyl substances (PFASs) were measured in samples from 1983 pregnant women enrolled in the Maternal-Infant Research on Environmental Chemicals (MIREC) cohort. Predictors of exposure were also identified. RESULTS: In maternal plasma, there was >90 % detection for the perfluoroalkyl substances (PFASs) perfluorooctanoic acid (PFOA), perfluoroctane sulfonate (PFOS), perfluorohexane sulfonate (PFHxS), and dichlorodiphenyldichloroethylene (DDE), oxychlordane and PCB 138 and 153. Cord blood plasma had much lower detection rates with low or very limited detection for most PCBs and PBDEs. The PFASs were the most frequently detected (23-64 %) chemical class in cord plasma. In a subset of 1st and 3rd trimester paired samples, PFAS concentrations were found to be strongly correlated and had ICCs ranging from 0.64 (PFOA) to 0.83 (PFHxS). The cord:maternal plasma concentration ratios ranged from 0.14 (PFOS) to 0.87 (oxychlordane, lipid adjusted). Similar to other studies, we found parity, maternal age, income, education, smoking status, pre-pregnancy BMI and fish consumption to be significant predictors for most chemicals. Those participants who were foreign-born had significantly higher concentrations of organochlorinated pesticides and PCBs. CONCLUSIONS: In the MIREC study, multiple chemical contaminants were quantified in the plasma of pregnant women. In cord plasma PFOA had the highest detection rate. However, compared to other Canadian and international population studies, the MIREC participants had lower contaminant concentrations of these substances.

Maternal and early life exposure to phthalates: The Plastics and Personal-care Products use in Pregnancy (P4) study.

Phthalates are a group of chemicals found in a number of consumer products; some of these phthalates have been shown to possess estrogenic activity and display anti-androgenic effects. While a number of biomonitoring studies of phthalates in pregnant women and infants have been published, there is a paucity of data based on both multiple sampling periods and in different matrices. Phthalate metabolites were measured in 80 pregnant women and their infants in Ottawa Canada (2009-2010) in urine, meconium and breast milk collected at various time periods pre- and post-parturition. At least 50% of the women had at least one urine sample greater than the limit of detection (LOD) for the various phthalate metabolites, with the exception of mono-n-octyl phthalate (MnOP), mono-isononyl phthalate (MiNP) and mono(carboxy-isooctyl) phthalate (MCiOP). Four major clusters of maternal urinary metabolites were identified. Among infants (n=61), the following metabolites were rarely (< 10%) detected: mono-cyclohexyl phthalate (MCHP), mono-isononyl phthalate (MiNP), mono-methyl phthalate (MMP), and mono-n-octyl phthalate (MnOP). While mono-benzyl phthalate (MBzP), mono-3-carboxypropyl phthalate (MCPP), MEHHP, and MEOHP were frequently detected in maternal urines at any time point, these metabolites were rarely detected in breast milk. Maternal urinary concentrations of MEP and the DEHP metabolites were higher in samples collected during pregnancy than postnatally. No statistically significant differences were observed in infant's urinary phthalate concentrations between breast-fed and bottle-fed infants. Significant correlations were observed between maternal urinary MEHHP (r=0.35), MEOHP (r=0.35) and MEP (r=0.37) collected at <20weeks gestation with levels in meconium and between MBzP (r=0.78) and MEP (r=0.56) in maternal and infant urine collected 2-3months after birth. These results suggest at least some maternal-fetal-infant transfer of phthalates and that meconium may be a useful matrix for measuring in utero exposure to phthalates.

Temporal variability and sources of triclosan exposure in pregnancy.

BACKGROUND: Triclosan (TCS) is an antibacterial agent commonly added to personal care products. Some animal research studies have associated TCS exposure with androgenic and thyroid effects, as well as endocrine disruption, contact dermatitis and skin irritation. Limited Canadian data exist on exposure levels, temporal variability and sources of exposure to TCS, especially among pregnant women. METHODS: Single and serial spot urine samples (n=1249), as well as consumer product use information were collected over 5 study visits across pregnancy and post-partum from 80 healthy pregnant women in Ottawa, Canada. Urine samples were analyzed for TCS by GC-MS-MS. Summary statistics, linear mixed effects models, and surrogate category analysis were used to describe the results. RESULTS: Triclosan was detected in 87% of maternal urine samples (LOD=3.0µg/L). The geometric mean TCS concentration of all urine samples was 21.6µg/L (95% CI 18.2-25.7). Triclosan concentrations were significantly higher when the urine was collected before 16:00, in the autumn, and more than 90min since last void, and in nulliparous women with household incomes greater than $100,000. A significant correlation was observed between maternal urinary TCS concentrations and number of reported uses of TCS-containing products. The ability of a single spot urine sample collected at any time during or post-pregnancy to predict an individual's geometric mean urinary TCS level corresponding to low, medium, or high exposure was 86.7%. Intraclass correlation coefficients indicated high reproducibility within a week-day (0.77) and week-end day (0.79) and moderate reproducibility across the study period (0.50). CONCLUSIONS: This study provided the first data on temporal variability of urinary TCS concentrations and predictors of exposure in Canadian pregnant women. These results can inform exposure assessments in pregnant women and justify collection of single spot urine samples in epidemiologic studies, especially for women with higher exposures.

Bisphenol A and phthalate metabolite urinary concentrations: Daily and across pregnancy variability.

Phthalates and bisphenol A (BPA) are high production volume and ubiquitous chemicals that are quickly metabolized in the body. Traditionally, studies have relied on single spot urine analyses to assess exposure; ignoring variability in concentrations throughout a day or over a longer period of time. We compared BPA and phthalate metabolite results from urine samples collected at five different time points. Participants (n=80) were asked to collect all voids in a 24 h period on a weekday and then again on a weekend before 20 weeks of pregnancy. During the second and third trimesters and in the postpartum period, single spot urines were collected. Variability over time in urinary concentrations was assessed using intraclass correlation coefficients (ICCs) and the sensitivity to correctly classify a single sample as high or low versus the geometric mean (GM) of all samples was calculated. We found low reproducibility and sensitivity of BPA and all phthalate metabolites throughout pregnancy and into the postpartum period but much higher reproducibility within a day. Time of day when the urine was collected was a significant predictor of specific gravity adjusted exposure levels. We concluded that, if the interest is in average exposures across pregnancy, maternal/fetal exposure estimation may be more accurate if multiple measurements, collected across the course of the entire pregnancy, rather than a single spot measure, are performed.

Exposure to free and conjugated forms of bisphenol A and triclosan among pregnant women in the MIREC cohort.

BACKGROUND: Bisphenol A (BPA) and triclosan (TCS) are two nonpersistent chemicals that have been frequently measured in spot urine samples from the general population but less so in pregnant women; however, data are limited on the free (bioactive) and conjugated forms of these phenols. OBJECTIVES: The Maternal-Infant Research on Environmental Chemicals (MIREC) Study addressed these data gaps by utilizing stored maternal urine samples from a large multicenter cohort study of Canadian pregnant women. METHODS: Concentrations of free and conjugated forms of BPA and TCS were measured in about 1,890 first-trimester urine samples by ultra performance liquid chromatography-tandem mass spectrometry using isotope dilution. RESULTS: The glucuronides of BPA and TCS were the predominant forms of these chemicals measured (detected in 95% and 99% of samples, respectively), whereas the free forms were detected in 43% and 80% of samples, respectively. The geometric mean urinary concentrations for glucuronides of BPA and TCS were 0.80 µg/L (95% CI: 0.75, 0.85) and 12.30 µg/L (95% CI: 11.08, 13.65), respectively. Significant predictors of BPA included maternal age < 25 vs. ≥ 35 years, current smoking, low vs. high household income, and low vs. high education. For TCS, urinary concentrations were significantly higher in women ≥ 25 years of age, never vs. current smokers, and women with high household income and high education. CONCLUSIONS: The results from this study represent the largest national-level data on urinary concentrations of free and conjugated forms of BPA and TCS in pregnant women and suggest that maternal characteristics predicting elevated urinary concentrations of these phenols largely act in opposite directions.

Maternal and infant exposure to environmental phenols as measured in multiple biological matrices.

BACKGROUND: Results of recent national surveys have shown the high prevalence of exposure to bisphenol A (BPA) and triclosan (TCS) among the general population; however biomonitoring data for pregnant women and infants are limited. METHODS: Women (n=80) were recruited from early prenatal clinics and asked to collect urine samples multiple times during pregnancy and once 2-3 months post-partum. Samples of infant urine and meconium as well as breast milk and infant formula were also collected. Biospecimens were analyzed by GC-MS/MS for BPA, TCS and triclocarban (TCC). RESULTS: Triclosan was detected in over 80% of the maternal urines (geometric mean (GM): 21.61 µg/L), 60% of the infant urines (GM: 2.8 µg/L), 46% of the breast milk and 80% of the meconium samples. Triclocarban was rarely detected in any of the biospecimens. Median total BPA concentrations were 1.21 and 0.24 µg/L in maternal and infant urines, respectively. Free BPA was detected in only 11% of infant urine samples. The meconium of female infants had significantly higher concentrations of total BPA and TCS than those of males, while no differences were observed in infant urine concentrations by sex. CONCLUSIONS: We found widespread exposure among pregnant women and infants to environmental phenols, with large inter-individual variability in exposure to triclosan. These data will contribute to the risk assessment of these chemicals, especially in susceptible sub-populations.

Phthalate and bisphenol A exposure among pregnant women in Canada--results from the MIREC study.

Bisphenol A (BPA) and phthalates are endocrine disruptors possibly linked to adverse reproductive and neurodevelopmental outcomes. These chemicals have commonly been measured in urine in population surveys; however, such data are limited for large populations of pregnant women, especially for the critical first trimester of pregnancy. The aim of the study was to measure BPA and phthalate metabolites in first trimester urine samples collected in a large national-scale pregnancy cohort study and to identify major predictors of exposure. Approximately 2000 women were recruited in the first trimester of pregnancy from ten sites across Canada. A questionnaire was administered to obtain demographic and socio-economic data on participants and a spot urine sample was collected and analyzed for total BPA (GC-MS/MS) and 11 phthalate metabolites (LC-MS/MS). The geometric mean (GM) maternal urinary concentration of total BPA, uncorrected for specific gravity, was 0.80 (95% CI 0.76-0.85) µg/L. Almost 88% of the women had detectable urinary concentrations of BPA. An analysis of urinary concentrations of BPA by maternal characteristics with specific gravity as a covariate in the linear model showed that the geometric mean concentrations: (1) decreased with increasing maternal age, (2) were higher in current smokers or women who quit during pregnancy compared to never smokers, and (3) tended to be higher in women who provided a fasting urine sample and who were born in Canada, and had lower incomes and education. Several of the phthalate metabolites analyzed were not prevalent in this population (MCHP, MMP, MiNP, MOP), with percentages detectable at less than 15%. The phthalate metabolites with the highest measured concentrations were MEP (GM: 32.02 µg/L) and MnBP (GM: 11.59 µg/L). MBzP urinary concentrations decreased with maternal age but did not differ by time of urine collection; whereas the DEHP metabolites tended to be higher in older women and when the urine was collected later in the day. This study provides the first biomonitoring results for the largest population of pregnant women sampled in the first trimester of pregnancy. The results indicate that exposure among this population of pregnant women to these chemicals is comparable to or even lower than that observed in a Canadian national population-based survey.

Urinary and breast milk biomarkers to assess exposure to naphthalene in pregnant women: an investigation of personal and indoor air sources.

BACKGROUND: Naphthalene exposures for most non-occupationally exposed individuals occur primarily indoors at home. Residential indoor sources include pest control products (specifically moth balls), incomplete combustion such as cigarette smoke, woodstoves and cooking, some consumer and building products, and emissions from gasoline sources found in attached garages. The study aim was to assess naphthalene exposure in pregnant women from Canada, using air measurements and biomarkers of exposure. METHODS: Pregnant women residing in Ottawa, Ontario completed personal and indoor air sampling, and questionnaires. During pregnancy, pooled urine voids were collected over two 24-hour periods on a weekday and a weekend day. At 2-3 months post-birth, they provided a spot urine sample and a breast milk sample following the 24-hour air monitoring. Urines were analyzed for 1-naphthol and 2-naphthol and breast milk for naphthalene. Simple linear regression models examined associations between known naphthalene sources, air and biomarker samples. RESULTS: Study recruitment rate was 11.2% resulting in 80 eligible women being included. Weekday and weekend samples were highly correlated for both personal (r = 0.83, p < 0.0001) and indoor air naphthalene (r = 0.91, p < 0.0001). Urine specific gravity (SG)-adjusted 2-naphthol concentrations collected on weekdays and weekends (r = 0.78, p < 0.001), and between pregnancy and postpartum samples (r = 0.54, p < 0.001) were correlated.Indoor and personal air naphthalene concentrations were significantly higher post-birth than during pregnancy (p < 0.0001 for signed rank tests); concurrent urine samples were not significantly different. Naphthalene in breast milk was associated with urinary 1-naphthol: a 10% increase in 1-naphthol was associated with a 1.6% increase in breast milk naphthalene (95% CI: 0.2%-3.1%). No significant associations were observed between naphthalene sources reported in self-administered questionnaires and the air or biomarker concentrations. CONCLUSIONS: Median urinary concentrations of naphthalene metabolites tended to be similar to (1-naphthol) or lower (2-naphthol) than those reported in a Canadian survey of women of reproductive age. Only urinary 1-naphthol and naphthalene in breast milk were associated. Potential reasons for the lack of other associations include a lack of sources, varying biotransformation rates and behavioural differences over time.

Cohort profile: the maternal-infant research on environmental chemicals research platform.

BACKGROUND: The Maternal-Infant Research on Environmental Chemicals (MIREC) Study was established to obtain Canadian biomonitoring data for pregnant women and their infants, and to examine potential adverse health effects of prenatal exposure to priority environmental chemicals on pregnancy and infant health. METHODS: Women were recruited during the first trimester from 10 sites across Canada and were followed through delivery. Questionnaires were administered during pregnancy and post-delivery to collect information on demographics, occupation, life style, medical history, environmental exposures and diet. Information on the pregnancy and the infant was abstracted from medical charts. Maternal blood, urine, hair and breast milk, as well as cord blood and infant meconium, were collected and analysed for an extensive list of environmental biomarkers and nutrients. Additional biospecimens were stored in the study's Biobank. The MIREC Research Platform encompasses the main cohort study, the Biobank and follow-up studies. RESULTS: Of the 8716 women approached at early prenatal clinics, 5108 were eligible and 2001 agreed to participate (39%). MIREC participants tended to smoke less (5.9% vs. 10.5%), be older (mean 32.2 vs. 29.4 years) and have a higher education (62.3% vs. 35.1% with a university degree) than women giving birth in Canada. CONCLUSIONS: The MIREC Study, while smaller in number of participants than several of the international cohort studies, has one of the most comprehensive datasets on prenatal exposure to multiple environmental chemicals. The biomonitoring data and biological specimen bank will make this research platform a significant resource for examining potential adverse health effects of prenatal exposure to environmental chemicals.

Circulating metals and persistent organic pollutant concentrations in Canadian and non-Canadian born primiparous women from five Canadian centres: results of a pilot biomonitoring study.

The developing foetus is thought to be at increased risk from exposure to environmental contaminants; however, developmental exposure data is notably lacking for many contaminants. Moreover, potential regional differences or effect of place of birth on residue levels measured in pregnant women is also unknown. Therefore, as part of a multinational biomonitoring study, 125 primiparous pregnant Canadian women were recruited from five Canadian centres (Vancouver, Calgary, Hamilton, Ottawa, and Halifax). Metals in whole blood and persistent organic pollutants (POPs) in plasma were measured by inductively coupled plasma mass spectrometry (ICPMS) and gas chromatography-mass spectrometry (GCMS), respectively. Of the 125 women recruited to this study, complete data sets were available for 123 of which 103 were Canadian born. Data were analysed by analysis of covariance and linear mixed models using age and body mass index as covariates. The metals cadmium (Cd), cobalt (Co), lead (Pb), nickel (Ni), selenium (Se), and total mercury (Hg) were detected in more than 93% of the samples tested. ß-Hexachlorohexane (ß-HCH), oxychlordane, trans-nonachlor, 1,1-dichloro-2,2-bis(p-chlorophenyl)ethylene (p,p'-DDE), polybrominated diphenyl ether (PBDE) congeners (PBDE-153, PBDE-47), polychlorinated biphenyl (PCB) congeners (PCB-138, -153, and -180), and the dioxin-like PCB congener PCB-118 were quantified in greater than 70% of the samples tested. Significant differences in the concentrations of Cd, Ni, PCB-153, and p,p'-DDE were found between the centres studied. Furthermore, foreign-born pregnant women had significantly higher concentrations of Cd, ß-HCH, PBDE-47, PCB-138, -153, -180, and p,p'-DDE compared to Canadian born pregnant women. Taken together, the data suggest that there are potential regional differences in contaminant body burden and place of birth may also contribute to differences in maternal residue concentrations.

Accuracy investigation of phthalate metabolite standards.

Phthalates are ubiquitous compounds whose metabolites are usually determined in urine for biomonitoring studies. Following suspect and unexplained results from our laboratory in an external quality-assessment scheme, we investigated the accuracy of all phthalate metabolite standards in our possession by comparing them with those of several suppliers. Our findings suggest that commercial phthalate metabolite certified solutions are not always accurate and that lot-to-lot discrepancies significantly affect the accuracy of the results obtained with several of these standards. These observations indicate that the reliability of the results obtained from different lots of standards is not equal, which reduces the possibility of intra-laboratory and inter-laboratory comparisons of results. However, agreements of accuracy have been observed for a majority of neat standards obtained from different suppliers, which indicates that a solution to this issue is available. Data accuracy of phthalate metabolites should be of concern for laboratories performing phthalate metabolite analysis because of the standards used. The results of our investigation are presented from the perspective that laboratories performing phthalate metabolite analysis can obtain accurate and comparable results in the future. Our findings will contribute to improving the quality of future phthalate metabolite analyses and will affect the interpretation of past results.

A prospective study of organochlorines in adipose tissue and risk of non­Hodgkin lymphoma.

BACKGROUND: Exposure to organochlorines has been examined as a potential risk factor for non-Hodgkin lymphoma (NHL), with inconsistent results that may be related to limited statistical power or to imprecise exposure measurements. OBJECTIVE: Our purpose was to examine associations between organochlorine concentrations in prediagnostic adipose tissue samples and the risk of NHL. METHODS: We conducted a case­cohort study using a prospective Danish cohort of 57,053 persons enrolled between 1993 and 1997. Within the cohort we identified 256 persons diagnosed with NHL in the population-based nationwide Danish Cancer Registry and randomly selected 256 subcohort persons. We measured concentrations of 8 pesticides and 10 polychlorinated biphenyl (PCB) congeners in adipose tissue collected upon enrollment. Associations between the 18 organochlorines and NHL were analyzed in Cox regression models, adjusting for body mass index. RESULTS: Incidence rate ratios and confidence intervals (CIs) for interquartile range increases in concentrations of dichlorodiphenyltrichlorethane (DDT), cis-nonachlor, and oxychlordane were 1.35 (95% CI: 1.10, 1.66), 1.13 (95% CI: 0.94, 1.36), and 1.11 (95% CI: 0.89, 1.38), respectively, with monotonic dose­response trends for DDT and cis-nonachlor based on categorical models. The relative risk estimates were higher for men than for women. In contrast, no clear association was found between NHL and PCBs. CONCLUSION: We found a higher risk of NHL in association with higher adipose tissue levels of DDT, cis-nonachlor, and oxychlordane, but no association with PCBs. This is the first study of organochlorines and NHL using prediagnostic adipose tissue samples in the exposure assessment and provides new environmental health evidence that these organochlorines contribute to NHL risk.