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

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.

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.

Dichlorodiphenyltrichloroethane and risk of hepatocellular carcinoma.

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.

Plasma levels of polychlorinated biphenyls and risk of cutaneous malignant melanoma: a preliminary study.

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.

Predictors of polychlorinated biphenyl concentrations in adipose tissue in a general Danish population.

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.

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.

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.

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.

An interlaboratory study of perfluorinated alkyl compound levels in human plasma.

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.

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.

Spring-harvested game birds from the western James Bay region of northern Ontario, Canada: organochlorine concentrations in breast muscle.

Although studies have assessed organochlorine concentration in breast tissue (pectoral muscle) of fall-harvested game birds in Canada, data for spring-harvested game birds are limited, especially for remote sub-arctic areas. Taking into account that most traditional Aboriginal diets include a large number of spring-harvested game birds, there is a need to assess organochlorine concentration in spring-harvested water birds with respect to suitability for human consumption. We examined organochlorine concentrations in breasts of 20 mallard ducks (Anas platyrhynchos), 20 northern pintails (A. acuta), 21 Canada geese (Branta canadensis interior), and 20 lesser snow geese (Chen caerulescens caerulescens) harvested in the spring; summer-harvested shorebirds (godwits; Limosa spp.) were also assessed as these water birds are an important part of the game bird harvest for First Nation Cree of the western James Bay region of Ontario, Canada. The most frequently detected organochlorines in striated (pectoral) muscle were SigmaPCBs (sum of 14 congeners [CBs]) and SigmaDDT (sum of DDE and DDT) followed by SigmaCHL (sum of oxy-chlordane, cis- and trans-nonachlor) and hexachlorobenzene with beta-hexachlorocyclohexane being the least frequently detected. For organochlorines that had < or =70% of the samples with detectable concentrations of an organochlorine (i.e., CBs 105, 128, 156, 170, 180, 183, cis-nonachlor, DDT, and mirex), log-linear contingency modelling revealed that the dabbling ducks had significantly more than expected detectable concentrations of most organochlorines; by contrast, geese and shorebirds had significantly less than expected detectable concentrations of most organochlorines. ANOVA for organochlorines with frequency of detection > or =70% (i.e., Aroclor 1260, SigmaPCBs, CBs 118, 138, 153, 187, DDE, hexachlorobenzene, oxy-chlordane and trans-nonachlor) revealed significant differences between bird species: Breast tissue in snow geese contained significantly less organochlorines than Canada geese (Aroclor 1260, CBs 118, 138, and 153) and godwits (Aroclor 1260, CBs 138, 153); mallards had significantly higher concentrations compared to godwits (DDE, trans-nonachlor, and SigmaCHLs), Canada geese (oxy-chlordane and SigmaCHLs), and snow geese (oxy-chlordane, trans-nonachlor, SigmaCHLs); and pintails had elevated levels compared to snow geese (CB 153, oxy-chlordane, trans-nonachlor, and SigmaCHLs) and Canada geese (oxy-chlordane). However, none of the samples analyzed in the present study exceeded the consumption guideline for organochlorines in fish or poultry with most samples being orders of magnitude less than the consumption guideline even when compared to maxima. Thus, the present spring-harvested-game bird study supports previous studies of fall-harvested game birds that contend that pectoral muscle portions are safe to eat. Nevertheless, skin and fat associated with the breast muscle may be another matter.

Brain and blood mercury and selenium after chronic and developmental exposure to methylmercury.

Fish contain methylmercury and the potentially protective element, selenium. Blood and brain concentrations of these elements were determined in female rats after consuming AIN-93-based diets containing 0.06 or 0.6 ppm of selenium (Se) and drinking water containing 0, 0.5, or 5 ppm of mercury as methylmercury (MeHg) for 6 or 18 months. Brain and blood concentrations of mercury and selenium were also evaluated in neonates after gestational exposure. For adult rats in the high-Se, high-Hg condition, brain selenium content was 0.35 ppm and 1.8 ppm after 6 and 18 months, respectively, but for every other adult-onset condition, it was 0.1 ppm. Blood selenium varied less than two-fold despite a 10-fold difference in diet. After 6 months, mercury content in the brain showed a greater than 10-fold difference between the mercury groups, and interacted somewhat with dietary selenium. After 18 months, no mercury was detected in the brains of the 0.5 ppm groups, and their blood mercury also fell. For the 5.0 ppm groups, brain mercury increased slightly (low Se diet) or several-fold (high Se diet) over that seen at 6 months, and blood mercury also increased. Neonatal selenium concentrations were more labile than adults, and mercury in neonates was generally higher. All animals exposed to 5 ppm of mercury experienced a molar excess of mercury over selenium. Animals exposed to 0.5 ppm mercury showed a balance between mercury and selenium or a selenium excess, depending on the condition.

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.

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.

Adipose organochlorine concentrations and risk of breast cancer among postmenopausal Danish women.

OBJECTIVE: Exposure to environmental organochlorines has been examined as a potential risk factor for human breast cancer with mixed results. Our purpose was to examine associations between organochlorines and the development of breast cancer in a large prospective study using stored adipose tissue. METHODS: We conducted a nested case-control study of 409 postmenopausal women who developed breast cancer and 409 controls selected from the 29,875 women enrolled in the Danish Diet, Cancer, and Health cohort between 1993 and 1997. We measured concentrations of 14 pesticides and 18 polychlorinated biphenyls in adipose tissue, collected upon enrollment, and estimated relative risk (RR) of breast cancer using conditional logistic regression. RESULTS: The results showed no higher risk of breast cancer among women with higher levels of any pesticides or polychlorinated biphenyls; the RR associated with the upper quartile of 1,1-dichloro-2, 2-bis(p-chlorophenyl)ethylene concentration was 0.7 [95% confidence interval (95% CI), 0.5-1.2] contrasting the lower quartile, and for the sum of polychlorinated biphenyls the similar risk was 1.1 (95% CI, 0.7-1.7). We observed a pattern of substantially lower risk of estrogen receptor-negative breast cancer in association with higher levels of most of the pesticides and polychlorinated biphenyls; the RR for the higher quartile of 1,1-dichloro-2,2-bis(p-chlorophenyl)ethylene was 0.1 (95% CI, 0.0-0.5) and for the sum of polychlorinated biphenyls it was 0.3 (95% CI, 0.1-0.9). CONCLUSION: The results do not support that higher organochlorine body levels increase the risk of breast cancer in postmenopausal women. The interpretation of the inverse association for estrogen receptor-negative breast cancer is currently unclear.

Isotope dilution-mass spectrometry determination of blood cyanide by headspace gas chromatography.

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.

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.