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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.

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.

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.

The aim of this study was to replace 75% of total fish oil (FO) and alter digestible protein/digestible energy (DP/DE) in rainbow trout feeds to minimize potentially hazardous environmental contaminant exposure. Two diets differing in DP/DE ratios (18 and 25) were combined with soybean (SO), canola (CO), and a blend of canola oil and Schizochytrium sp. (COS). Dietary lipids and DP/DE ratios did not affect apparent digestibility, growth, and somatic parameters. The n-3/n-6 levels decreased significantly in the growth trial, especially for the SO groups. A short washout trial restored n-3/n-6 levels for the CO and COS groups, irrespective of the DP/DE ratio, but not for the SO groups. At all sampling events, contaminant concentrations in fish flesh were lower than limits set by regulatory agencies in Canada, the US, and Europe. Contaminants were lower in the oil replacement diets compared to FO for toxaphenes, organochlorine pesticides, and PCBs but not flame retardants during the growth phase. At the end of the washout phase, no differences were detected. Thus, this study revealed that replacing 75% of total fish oil in rainbow trout feed by CO and COS, combined with a 25 DP/DE ratio, with a washout period seems to be the most efficient approach in terms of maximizing the total FO replacement and contribute to reducing POPs exposure.

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 = 3.0 μg/L). The geometric mean TCS concentration of all urine samples was 21.6 μg/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 90 min 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.

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 chromatograpy–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. Citation: Arbuckle TE, Marro L, Davis K, Fisher M, Ayotte P, Bélanger P, Dumas P, LeBlanc A, Bérubé R, Gaudreau É, Provencher G, Faustman EM, Vigoren E, Ettinger AS, Dellarco M, MacPherson S, Fraser WD. 2015. Exposure to free and conjugated forms of bisphenol A and triclosan among pregnant women in the MIREC cohort. Environ Health Perspect 123:277–284; http://dx.doi.org/10.1289/ehp.1408187

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.

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.

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. Electronic supplementary material The online version of this article (doi:10.1186/s12940-016-0143-y) contains supplementary material, which is available to authorized users.

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.

Dichlorodiphenyltrichloroethane (p,p'-DDT), an organochlorine pesticide known to have deleterious health effects in humans, has been linked to hepatocellular carcinoma (HCC) in rodents. A recent study has reported that p,p'-DDT and its most persistent metabolite, dichlorodiphenyldichloroethylene (p,p'-DDE), may also be associated with HCC in humans. To examine whether there is an association between p,p'-DDT and/or p,p'-DDE in a population at high-risk of developing HCC, a nested case-control study was conducted within the 83,794 person Haimen City Cohort in China. Sera and questionnaire data were collected from all participants between 1992 and 1993. This study included 473 persons who developed HCC and 492 who did not, frequency matched on sex, age and area of residence. p,p'-DDT and p,p'-DDE levels were determined by mass spectrometry. Hepatitis B viral infection status (based on hepatitis B virus surface antigen; HBsAg) was also determined. p,p'-DDT and/or p,p'-DDE serum levels were significantly associated with sex, area of residence, occupation, alcohol consumption and cigarette smoking. Adjusting for age, sex, area of residence, HBsAg, family history of HCC, history of acute hepatitis, smoking, alcohol, occupation (farmer vs. other) and levels of p,p'-DDT or p,p'-DDE, odds ratios (OR) and 95% confidence intervals (CI) were calculated via unconditional logistic regression. Overall, the highest quintile of p,p'-DDT was associated with an increased risk of HCC, OR = 2.96 95% CI; 1.19-7.40. There were no statistically significant associations with p,p'-DDE. Overall, these results suggest that recent exposure to p,p'-DDT may increase risk of HCC.

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

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 case–cohort 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 dose–response 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.

Background: Concerns regarding the persistence, bioaccumulation, long-range transport, and adverse health effects of polybrominated dipheyl ethers (PBDEs) have recently come to light. PBDEs may potentially be of concern to indigenous (First Nations) people of Canada who subsist on traditional foods, but there is a paucity of information on this topic. Objectives and methods: To investigate whether the traditional diet is a major source of PBDEs in sub-Arctic First Nations populations of the Hudson Bay Lowlands (James and Hudson Bay),Ontario, Canada, a variety of tissues from wild game and fish were analyzed for PBDE content (n=147) and dietary exposure assessed and compared to the US EPA reference doses (RfDs). In addition, to examine the effect of isolation/industrialization on PBDE body burdens, the blood plasma from three First Nations (Cree Nation of Oujé-Bougoumou, Quebec; Fort Albany First Nation, Ontario; and Weenusk First Nation [Peawanuck], Ontario, Canada) were collected (n=54) and analyzed using a log-linear contingency model. Results and conclusions: The mean values of PBDEs in wild meats and fish adjusted for standard consumption values and body weight, did not exceed the US EPA RfD. Log linear modeling of the human PBDE body burden showed that PBDE body burden increases as access to manufactured goods increases. Thus, household dust from material goods containing PBDEs is likely responsible for the human exposure; the traditional First Nations diet appears to be a minor source of PBDEs. Keywords: Polybrominated diphenyl ethers, PBDE, First Nations, Aboriginal, Diet, Subsistence

A number of epidemiologic studies have suggested that exposure to polychlorinated biphenyls (PCB) and other organochlorine compounds (OCC) increase risk of cutaneous malignant melanoma (CMM). However, these studies have generally had no biologic measure of OCC exposure, and have been unable to control for sun exposure, the major known environmental risk factor for this disease. This preliminary study examined the relationship between OCC residues in plasma and risk of CMM adjusting for sun sensitivity and sun exposure. A case-control study of 80 CMM patients and 310 control subjects was conducted. Lifetime sun exposure information, along with data on pigmentation variables and sun sensitivity data was collected, along with a blood sample. Cases and controls were assayed for plasma levels of 14 PCB congeners and 11 organochlorine pesticide residues using gas chromatography. Strong associations were seen between risk of CMM and plasma levels of non-dioxin-like PCBs (Adjusted OR = 7.02; 95% CI: 2.30-21.43 for highest quartile) and several PCB congeners, organochlorine pesticides or metabolites. These associations persisted after control for sun sensitivity and sun exposure. Results from this investigation require independent confirmation in larger studies. However, they suggest that environmental factors other than UV radiation may play a role in genesis of CMM, and indicate that it may be productive to search for further agents which might increase risk.

A critical issue in the organisation of Proficiency Testing/External Quality Assessment Schemes is the definition of the criteria against which the performance of individual laboratories should be evaluated. Organisers of EQAS in Occupational and Environmental Laboratory Medicine ( http://www.occupational-environmental-laboratory.com ) collaborate to define common acceptable levels of performance. The aim of this study was to compare the Horwitz function to the Fraser’s approach. Sets of results obtained from the distribution of test materials in the Network schemes (for the measurands: copper, selenium or zinc in serum) were used to calculate Z-scores according to both approaches. Quality specifications derived from both approaches were also compared to the standard deviations obtained. Except for selenium, Horwitz criteria suggests a more stringent evaluation than Fraser criteria, the latter being very stringent as regard the participant analytical variability.

An under-recovery of inorganic mercury added to urine and a wide range of results is observed in quality assessment schemes (EQAS) for trace elements. Further- more, the under-recoveries are inconsistent suggesting features associated with the urine matrix may make the mercury unavailable for measurement. To investigate the instability of mercury in urine the following experiments were set up: (1) a sample of Hg 2? in water with various 'stabilizers' added was sent to UK external quality assessment scheme participants. (2) Urine was collected from volunteers who also completed a 3-day food diary. Hg, Ca, Mg, Se, uric acid, phosphate, creatinine, reducing substances and protein were measured. Inorganic mercury was spiked into the urine, stabilizers were added and the mercury determined following storage. The results con- firmed under-recovery of mercury in association with the urine matrix. Further investigations of how urinary com- ponents affect the measurement of mercury are necessary.

We conducted two surveys of Ontario (Canada) fishers: a stratified sample of licensed anglers in two Lake Ontario communities (anglers, n=232) and a shore and community-based sample in five Great Lakes' Areas of Concern (AOC eaters, n=86). Among the 176 anglers consuming their catch, the median number of sport-fish meals/year was 34.2 meals and 10.9, respectively, in two communities, with a mean blood total mercury level among these sport-fish consumers of 2.8 microg/L. The vast majority of fish eaten by AOC eaters was from Ontario waters (74%). For AOC eaters, two broad country-of-origin groups were assembled: Euro-Canadians (EC) and Asian-Canadians (AC). EC consumed a median of 174 total fish meals/year and had a geometric mean total mercury level of 2.0 microg/L. Corresponding AC figures were 325 total fish meals/year and 7.9 microg/L. Overall, mercury levels among AOC eaters were higher than in many other Great Lakes populations but lower than in populations frequently consuming seafood. In multivariate models, mercury levels were significantly associated with levels of fish consumption among both anglers and EC AOC eaters. Given the nutritional and social benefits of fish consumption, prudent species and location choices should continue.

Popular shampoos were screened for their contents in trace elements, using ICP-MS detection in a semi-quantitative mode. Hair samples from volunteers were analyzed before and after hair washing with selected shampoos to demonstrate the effect of the contamination and the impact on occupational medicine. While some shampoos showed high levels of certain elements, the degree of contamination on the hair was found to be negligible. Only one shampoo tested, formulated with selenium sulfide, was found to seriously contaminate the hair.

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.

Suppose there are k sets each containing n lines in the plane. One might be interested in locating the points intersected by at least one line from each set. This paper describes an algorithm which locates all those vertices using O(kn2) time and O(kn) space. The method relies heavily on the topological plane sweep of Edelsbrunner and Guibas (1989).

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. β-Hexachlorohexane (β-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, β-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.

Chloroform is a known contaminant of chlorinated drinking water and of swimming pool water disinfected with chlorine or one of its derivatives. Few data exist regarding the importance of dermal and inhalation exposure routes to the chloroform body burden resulting from domestic and recreational use of chlorinated water. In our experimental study involving 11 male swimmers, we quantified the body burden resulting from exposure to various concentrations of chloroform in water and air of an indoor swimming pool, during a daily 55-min exercise period. From the first to the sixth exercise period, CHCl3 mean concentration in water was increased from 159 micrograms/l to 553 micrograms/l. Corresponding mean air CHCl3 level ranged from 597 ppb to 1630 ppb. To dissociate the dermal exposure route from that of inhalation, swimmers used scuba tanks during an additional exercise period. Chloroform concentrations were measured in alveolar air before and after each exercise period, as well as after 35 min of physical activity. Chloroform levels in water and air were measured every 10 min. We examined the relationship between alveolar air concentration (a measure of body burden) at 35 and 55 min and environmental chloroform concentrations by using multiple regression models. The natural logarithm of alveolar air concentration was strongly correlated with aqueous chloroform concentration both at 35 (p2 < 0.001, r2 = 0.75) and 55 min (p < 0.001, r2 = 0.86). The relationship with air concentrations was also statistically significant (35 min: p < 0.001, r2 = 0.58, 55 min: p < 0.001, r2 = 0.63).(ABSTRACT TRUNCATED AT 250 WORDS) Images Figure 1. Figure 2. A Figure 2. B Figure 3. A Figure 3. B

Organochlorine pesticides are ubiquitously present in the environment and suspected of carcinogenic, neurological and immunological effects. Our objective was to identify determinants of adipose tissue levels of organochlorine pesticides experienced by a general Danish population. Adipose tissue was collected upon enrolment of 245 randomly selected persons from a prospective cohort of 57,053 persons enrolled between 1993 and 1997. We examined geography, gender, age, lactation, body mass index (BMI) and intake of nine dietary groups and tap water drinks, as potential determinants of dichlorodiphenyltrichloroethane (DDT), dichlorodiphenyldichloroethylene, hexachlorocyclohexane, dieldrin, hexachlorobenzene, cis-nonachlor, trans-nonachlor and oxychlordane. Living in Copenhagen city and age at enrolment showed positive associations with all compounds. BMI was positively associated with all compounds except cis-nonachlor. Fatty-fish consumption showed positive associations with cis-nonachlor, trans-nonachlor, DDT and dieldrin and fruit and vegetables were inversely associated with dieldrin. Determinant estimates of trans-nonachlor were similar to estimates of total chlordanes while cis-nonachlor and oxychlordane seemed to differ. This is one of the first studies of organochlorine pesticides predictors in adipose tissue and contributes to the ongoing debate about exposure sources of these compounds. Single determinants varied among the individual compounds, even within related chlordane residues, suggesting that organochlorine pesticides should not be treated as a homogenous group.

Polychlorinated biphenyls (PCBs) are ubiquitously present in the environment and suspected of carcinogenic, neurological, and immunological effects. Our purpose was to identify predictors of adipose tissue levels of mono-, di-, and tri-ortho-substituted PCBs experienced by a general population and to establish whether predictors vary according to substitution group. In this study of 245 randomly selected persons from a prospective Danish cohort of 57,053 persons, we examined geographical area, age, lactation, BMI, and intake of eight major dietary groups as potential determinants of adipose concentrations of mono-, di-, and tri-ortho-substituted PCBs by linear regression analyses. Lactation, BMI, and intake of fruit, vegetables, and dairy products showed negative associations with PCB concentrations in adipose tissue in all models, and living in Copenhagen city, age, and consumption of fish (particularly fatty fish) were positively associated. The associations between several of the predictors and mono-ortho-substituted PCBs tended to differ from the associations found for di- and tri-ortho-substituted PCBs. In conclusion, geography, age, lactation, BMI, and consumption of fatty fish consistently predicted the concentration of PCBs in adipose tissue. Our results indicate that predictors of PCBs varied according to substitution group, suggesting that ortho-substituted groups should be analyzed separately.

Resume La grande disparite des reglementations relatives aux reactifs de laboratoire destines aux analyses de biologie medicale qui existaient a la fin des annees 1980 dans les pays de l'Union europeenne rendait indispensable une harmonisation qui n'a pas ete facile. Au terme d'une longue discussion dans laquelle la France a essaye de faire prevaloir son experience, la directive qui vient d'etre publiee est le resultat d'un compromis entre les soucis d'une libre circulation des industriels et les soucis de securite tout aussi naturels des autorites sanitaires de la France en particulier. C'est maintenant la Loi europeenne et il va falloir la mettre en œuvre.

We conducted an interlaboratory study which differed from the typical study of this type because of its emphasis on comparing intralaboratory variability in results. We sent specimens to six laboratories experienced in the analysis of perfluorinated alkyl compounds in blood matrices and that use stringent procedures to control and assure accuracy and precision. Each received an identical set of 60 plasma specimens that were analyzed in six completely independent batches. Split specimens were included so that within- and between-batch coefficients of variation could be calculated. All laboratories used liquid chromatography-tandem mass spectrometry (LC-MS/MS). The concentrations of perfluorooctanesulfonate (PFOS), perfluorooctanoate (PFOA), and perfluorohexanesulfonate (PFHxS) measured in the specimens in general showed a high level of agreement, although in some cases the agreement was only moderate. The average within- and between-batch coefficient of variation for PFOS was 9.1% and 9.3%; for PFOA was 14.5% and 14.5%; and for PFHxS was 14.5% and 17.0%. The recent availability of labeled internal standards, among other advances, has facilitated improvement in the accuracy and precision of the assays. Considering the degree of between-subject variation in levels among people in background-exposed populations, the results indicate that biomarker-based epidemiologic studies of associations with health could have reasonable precision.

A direct and sensitive method for the determination of blood cyanide by isotope dilution was developed. The blood is placed in a headspace vial, and K13C15N is added as internal standard. Addition of phosphoric acid liberates the cyanide as HCN. The detection is accomplished by mass spectrometry after a fine mass calibration tuning. The detection limit obtained is 0.3 micromol/L. The within- and inter-run coefficients of variation are 4.4% (for a concentration of 2.5 micromol/L) and 3.9% (for a concentration of 4.7 micromol/L), respectively. The observed recovery is 98%. A round-robin exercise was carried out to compare the performance of this method with others currently in use in other clinical laboratories.

Maternal and umbilical cord blood levels of mercury (Hg), lead (Pb), cadmium (Cd), and the trace elements copper (Cu), zinc (Zn), and selenium (Se) are reported for Inuit, Dene/Métis, Caucasian, and Other nonaboriginal participants from Arctic Canada. This is the first human tissue monitoring program covering the entire Northwest Territories and Nunavut for multiple contaminants and establishes a baseline upon which future comparisons can be made. Results for chlorinated organic pesticides and PCBs for these participants have been reported elsewhere. Between May 1994 and June 1999, 523 women volunteered to participate by giving their written informed consent, resulting in the collection of 386 maternal blood samples, 407 cord samples, and 351 cord:maternal paired samples. Geometric mean (GM) maternal total mercury (THg) concentrations ranged from 0.87 microg/L (SD = 1.95) in the Caucasian group of participants (n = 134) to 3.51 microg/L (SD = 8.30) in the Inuit group (n = 146). The GM of the Inuit group was 2.6-fold higher than that of the Dene/Métis group (1.35 microg/L, SD = 1.60, n = 92) and significantly higher than those of all other groups (P0.0001). Of Inuit women participants, 3% (n = 4) were within Health Canada's level of concern range (20-99 microg/L) for methylmercury (MeHg) exposure. Of Inuit and Dene/Métis cord samples, 56% (n = 95) and 5% (n = 4), respectively, exceeded 5.8 microg/L MeHg, the revised US Environmental Protection Agency lower benchmark dose. GM maternal Pb was significantly higher in Dene/Métis (30.9 microg/L or 3.1 microg/dL; SD = 29.1 microg/L) and Inuit (31.6 microg/L, SD = 38.3) participants compared with the Caucasian group (20.6 microg/L, SD = 17.9) (P0.0001). Half of all participants were smokers. GM blood Cd in moderate smokers (1-8 cigarettes/day) and in heavy smokers (8 cigarettes/day) was 7.4-fold higher and 12.5-fold higher, respectively, than in nonsmokers. The high percentage of smokers among Inuit (77%) and Dene/Métis (48%) participants highlights the need for ongoing public health action directed at tobacco prevention, reduction, and cessation for women of reproductive age. Pb and THg were detected in more than 95% of all cord blood samples, with GMs of 21 microg/L and 2.7 microg/L, respectively, and Cd was detected in 26% of all cord samples, with a GM of 0.08 microg/L. Cord:maternal ratios from paired samples ranged from 0.44 to 4.5 for THg, from 0.5 to 10.3 for MeHg, and 0.1 to 9.0 for Pb. On average, levels of THg, MeHg, and Zn were significantly higher in cord blood than in maternal blood (P0.0001), whereas maternal Cd, Pb, Se, and Cu levels were significantly higher than those in cord blood (P0.0001). There was no significant relationship between methylmercury and selenium for the range of MeHg exposures in this study. Ongoing monitoring of populations at risk and traditional food species, as well as continued international efforts to reduce anthropogenic sources of mercury, are recommended.

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