Environmental Chemicals Study Research Articles

Legacy halogenated flame retardants in Canadian human milk from the maternal-infant research on environmental chemicals study

Polybrominated diphenyl ethers (PBDEs) and hexabromocyclododecane (HBCD) were measured in 298 human milk samples collected from across Canada between 2008 and 2011 as part of the Maternal-Infant Research on Environmental Chemicals study. PBDEs were detected in 100% of the samples analyzed and concentrations ranged from 0.071 to 267 ng·g-1 lipid (median 15.6 ng·g-1 lipid). The dominant contributors to ΣPBDEs (Σ15, 17, 28, 37, 47, 66, 71, 75, 77, 85, 99, 100, 119, 138, 153, 154, 160, 183, 190, 209) were PBDE 47 > PBDE 153 > PBDE 99 > PBDE 100 > PBDE 28 > PBDE 209. Previously, PBDE 209 was considered to be a minor contributor to ΣPBDE concentrations in Canadian human milk and, therefore, not reported by our lab. This study showed that when present, PBDE 209 can be an important contributor to ΣPBDEs (range: below detection - 85.3 ng·g-1 lipid; median - 0.083 ng·g-1 lipid). ΣPBDE concentrations declined slightly in Canadian human milk between the early and late 2000s. HBCD (Σ of α-, β-, and γ-) was observed in 94.0% of the samples measured and concentrations were dominated by α-HBCD (93.3%), with β- (9.7%) and γ- (28.5%) less frequently detected. The maximum ΣHBCD concentration observed was 7.66 ng·g-1 lipid (median value 0.303 ng·g-1 lipid). These data suggest that HBCD concentrations similarly decreased in Canadian human milk between the early 2000s and sampling for the present study. Maternal age did not impact the concentrations of these flame retardants in milk. Additionally, other maternal characteristics [e.g., the number of children a woman has had, pre-pregnancy body mass index (BMI), and education level] did not impact concentrations of these brominated flame retardant concentrations.

A cohort study of the multipollutant effects of PM2.5, NO2, and O3 on C-reactive protein levels during pregnancy.

PM2.5, NO2, and O3 contribute to the development of adverse pregnancy complications. While studies have investigated the independent effects of these exposures, literature on their combined effects is limited. Our objective was to study the multipollutant effects of PM2.5, NO2, and O3 on maternal systemic C-reactive protein (CRP) levels. We used data from 1170 pregnant women enrolled in the Maternal-Infant Research on Environmental Chemicals Study (MIREC) study in Canada. Air pollution exposures were assigned to each participant based on residential location. CRP was measured in third-trimester blood samples. We fit multipollutant linear regression models and evaluated the effects of air pollutant mixtures (14-day averages) using repeated-holdout Weighted Quantile Sum (WQS) regression and by calculating the Air Quality Health Index (AQHI). In multipollutant models adjusting for NO2, O3, and green space, each interquartile range (IQR) increase in 14-day average PM2.5 (IQR: 6.9 µg/m3) was associated with 27.1% (95% confidence interval [CI] = 6.2, 50.7) higher CRP. In air pollution mixture models adjusting for green space, each IQR increase in AQHI was associated with 37.7% (95% CI = 13.9, 66.5) higher CRP; and an IQR increase in the WQS index was associated with 78.6% (95% CI = 29.7, 146.0) higher CRP. PM2.5 has the strongest relationship of the individual pollutants examined with maternal blood CRP concentrations. Mixtures incorporating all three pollutants, assessed using the AQHI and WQS index, showed stronger relationships with CRP compared with individual pollutants and illustrate the importance of conducting multipollutant analyses.

3 Fluoride Exposure and Hypothyroidism in Pregnant Women: A Potential Mechanism of Fluoride Neurotoxicity

Objective:Fluoride exposure has been associated with thyroid dysfunction, but fluoride's impact on thyroid function in pregnancy is unclear, especially during early gestation when the fetus is dependent on maternal thyroid hormone. We examined the potential thyroid-disrupting effects of maternal fluoride exposure in pregnancy and tested whether thyroid disruption in pregnancy mediates the association between maternal fluoride exposure and child intelligence quotient (IQ) among Canadian mother-child dyads living in areas with optimal fluoridation.Participants and Methods:We measured fluoride concentrations in drinking water and in spot urine samples collected in each trimester from pregnant women enrolled in the Maternal-Infant Research on Environmental Chemicals study. We also measured thyroid hormone (thyroid stimulating hormone [TSH], free thyroxine [FT4], and total thyroxine [TT4]) levels during the first trimester of pregnancy and categorized women as euthyroid (n=1301), subclinical hypothyroid (n=100), or primary hypothyroid (n=28). Those categorized as primary hypothyroid were combined with an additional 79 women who reported clinical diagnoses at time of study enrolment (total n=107). In a sample of 1508 women, we used logistic regression to estimate the association between fluoride exposure and risk of either subclinical or primary hypothyroidism, separately, and linear regression to estimate associations between fluoride exposure and women's thyroid hormone levels (TSH, FT4, TT4). We tested effect modification by child sex and thyroid peroxidase (TPO) antibody status. In a subsample of 439 mother-child pairs, we measured child Full-Scale IQ (FSIQ) at 3-4 years of age using the Wechsler Preschool and Primary Scale of Intelligence. We used linear regression to test associations between maternal hypothyroidism or thyroid hormone levels, and children's FSIQ scores. Finally, mediation analysis in the counterfactual framework was used to estimate the proportion of the effect of maternal fluoride exposure on child FSIQ mediated by maternal hypothyroidism, through evaluation of the natural direct (not through hypothyroidism) and indirect (through hypothyroidism) effects.Results:Using categorical measures of thyroid status, a 0.5 mg/L increase in water fluoride concentration was associated with a 1.64 (95% confidence interval [CI], 1.04 to 2.58) increased odds of primary hypothyroidism. This association was stronger among women with normal TPO antibody levels (< 5.61 IU/mL) (odds ratio, 2.80; 95% CI, 1.24 to 6.36). In contrast, we did not find a significant association between maternal urinary fluoride and hypothyroidism. For continuous measures of thyroid hormone levels, a 1 mg/L increase in maternal urinary fluoride was associated with a 35% (p=0.01) increase in TSH among women pregnant with a female fetus. In our subsample analyses, children born to women with primary hypothyroidism had lower FSIQ than children of euthyroid women, especially among boys (B, 8.78; 95% CI, -16.78 to -0.79). In contrast, maternal TSH, FT4, and TT4 levels were not significantly associated with child FSIQ scores. Maternal primary hypothyroidism did not significantly mediate the relationship between maternal water fluoride concentration and child FSIQ (p natural indirect effect= .35).Conclusions:Fluoride in drinking water may increase the risk of hypothyroidism in pregnancy. Thyroid dysfunction in pregnancy may be one mechanism underlying developmental neurotoxicity of fluoride.

Prenatal exposure to perfluoroalkyl substances and inflammatory biomarker concentrations.

We analyzed data from 1411 participants, recruited between 2008 and 2011, in the Maternal-Infant Research on Environmental Chemicals study. Our primary outcome was a composite inflammatory index derived by summing the z-scores of eight proinflammatory biomarkers. Using multivariable linear regression models, we quantified associations between each PFAS and the inflammatory index and individual biomarkers. We quantified the effects of the PFAS mixture using weighted quantile sum regression, and evaluated effect modification using product terms and sex-stratified models. Each doubling of PFOA and PFHxS was associated with a 0.38 (95% CI, 0.09, 0.67) and 0.21 (95% CI, 0.01, 0.41) SD increase in the proinflammatory index, respectively. A one-quartile increase in the PFAS mixture was associated with a 0.40 (95% CI, 0.09, 0.71) SD increase in the proinflammatory index. In individual models, we observed positive associations between PFAS and concentrations of monocyte chemoattractant protein-1, macrophage inflammatory protein-1β, and matrix metalloproteinases-9; however, the magnitude and precision varied according to the specific PFAS. Sex-specific findings were identified in few PFAS-biomarker associations. PFOA, PFOS, and PFHxS, individually and as a mixture, were positively associated with proinflammatory biomarkers during pregnancy.

Prenatal and concurrent blood mercury concentrations and associations with IQ in canadian preschool children

BackgroundPrenatal and childhood mercury (Hg) exposures have been associated with negative impacts on child neurodevelopment. It is unclear if associations persist at the low Hg exposures typical in Western countries. ObjectiveTo examine associations between prenatal/childhood blood Hg concentrations and child IQ in Canadian male and female children while considering the potential modifying role of prenatal fish consumption. MethodsWe analyzed data from the Maternal-Infant Research on Environmental Chemicals study. Hg was measured in first trimester (n = 527), cord (n = 430), and child (at 3–4 years of age, n = 355) blood and examined sex-stratified associations between blood Hg and children's Full Scale IQ (FSIQ), Verbal IQ (VIQ), Performance IQ (PIQ), and General Language Composite (GLC) scores (assessed with WPPSI-III). Prenatal Hg analyses were further stratified by prenatal fish consumption (low: 0–2, moderate: 3–7, or high: ≥8 times/month). ResultsHigher cord blood Hg concentrations were associated with lower PIQ (ß = −3.27; 95%CI: 6.44, −0.09) in male children with the lowest prenatal fish consumption. Progressively stronger positive associations were observed with PIQ in male children for moderate (ß = 1.08; 95%CI: 0.10, 2.26) and high (ß = 3.07; 95%CI: 1.95, 4.19) prenatal fish consumption. Cord blood Hg concentrations were positively associated with female children's FSIQ (ß = 1.29; 95% CI: 0.77, 1.81) and PIQ (ß = 2.01; 95% CI: 1.19, 2.83); however, when stratified only in the highest fish consumption subgroup. Among female children, higher child blood Hg concentrations were associated with an approximately 1-point increase in FSIQ, VIQ, and GLC. ConclusionsPrenatal exposure to low levels of Hg was associated with lower PIQ scores in male children with low prenatal fish intake. Positive associations between cord and child blood Hg concentrations and IQ were primarily observed in female children and may be due to beneficial effects of prenatal fish intake.

Association between toxic metals, vitamin D and preterm birth in the Maternal-Infant research on environmental chemicals study.

Toxic metals, like lead, are risk factors for preterm birth (PTB), but few studies have examined low levels found in most Canadians. Vitamin D, which may have antioxidant activity, protects against PTB. In this study, we investigated the impact of toxic metals (lead, mercury, cadmium and arsenic) on PTB and examined if maternal plasma vitamin D concentrations modify these associations. We investigated whether concentrations of metals in whole blood measured in early and late pregnancy were associated with PTB (<37 weeks) and spontaneous PTB in 1851 live births from the Maternal-Infant Research on Environmental Chemicals Study using discrete time survival analysis. We also investigated whether the risk of PTB was modified by first-trimester plasma 25-hydroxyvitamin D (25OHD) concentrations. Of 1851 live births, 6.1% (n= 113) were PTBs and 4.9% (n= 89) were spontaneous PTB. A 1μg/dL increase in blood lead concentrations during pregnancy was associated with an increased risk of PTB (relative risk [RR] 1.48, 95% confidence interval [CI] 1.00, 2.20) and spontaneous PTB (RR 1.71, 95% CI 1.13, 2.60). The risk was higher in women with insufficient vitamin D concentrations (25OHD <50 nmol/L) for both PTB (RR 2.42, 95% CI 1.01, 5.79) and spontaneous PTB (RR 3.04, 95% CI 1.15, 8.04). However, an interaction on the additive scale was not present. Arsenic was associated with a higher risk of PTB (RR 1.10, 95% CI 1.02, 1.19) and spontaneous PTB (RR 1.11, 95% CI 1.03, 1.20) per 1μg/L. Gestational exposure to low levels of lead and arsenic may increase the risk of PTB and spontaneous PTB; individuals with insufficient vitamin D may be more susceptible to the adverse effects of lead. Given our relatively small number of cases, we encourage testing of this hypothesis in other cohorts, especially those with vitamin D-deficient populations.

Fluoride exposure and hypothyroidism in a Canadian pregnancy cohort

BackgroundWhile fluoride can have thyroid-disrupting effects, associations between low-level fluoride exposure and thyroid conditions remain unclear, especially during pregnancy when insufficient thyroid hormones can adversely impact offspring development. ObjectivesWe evaluated associations between fluoride exposure and hypothyroidism in a Canadian pregnancy cohort. MethodsWe measured fluoride concentrations in drinking water and three dilution-corrected urine samples and estimated fluoride intake based on self-reported beverage consumption. We classified women enrolled in the Maternal-Infant Research on Environmental Chemicals Study as euthyroid (n = 1301), subclinical hypothyroid (n = 100) or primary hypothyroid (n = 107) based on their thyroid hormone levels in trimester one. We used multinomial logistic regression to estimate the association between fluoride exposure and classification of either subclinical or primary hypothyroidism and considered maternal thyroid peroxidase antibody (TPOAb) status, a marker of autoimmune hypothyroidism, as an effect modifier. In a subsample of 466 mother-child pairs, we used linear regression to explore the association between maternal hypothyroidism and child Full-Scale IQ (FSIQ) at ages 3-to-4 years and tested for effect modification by child sex. ResultsA 0.5 mg/L increase in drinking water fluoride concentration was associated with a 1.65 (95 % confidence interval [CI]: 1.04, 2.60) increased odds of primary hypothyroidism. In contrast, we did not find a significant association between urinary fluoride (adjusted odds ratio [aOR]: 1.00; 95%CI: 0.73, 1.39) or fluoride intake (aOR: 1.25; 95%CI: 0.99, 1.57) and hypothyroidism. Among women with normal TPOAb levels, the risk of primary hypothyroidism increased with both increasing water fluoride and fluoride intake (aOR water fluoride concentration: 2.85; 95%CI: 1.25, 6.50; aOR fluoride intake: 1.75; 95%CI: 1.27, 2.41). Children born to women with primary hypothyroidism had lower FSIQ scores compared to children of euthyroid women, especially among boys (B coefficient: −8.42; 95 % CI: −15.33, −1.50). DiscussionFluoride in drinking water was associated with increased risk of hypothyroidism in pregnant women. Thyroid disruption may contribute to developmental neurotoxicity of fluoride.

The association between metals, vitamin D and preterm birth in the MIREC Cohort Study

BACKGROUND Toxic metals, like lead, are risk factors for preterm birth (PTB), but few studies have explored this association at the low levels currently found in the Canadian population. Conversely, studies suggest that vitamin D may have antioxidant activity and protect against PTB. In this study, we sought to investigate associations between toxic metals (lead, mercury, cadmium and arsenic) and PTB, and to determine if maternal plasma vitamin D concentrations modify these associations. METHODS We investigated whether metals in whole blood measured in early and late pregnancy were associated with PTB (&amp;#x3c;37 weeks) and spontaneous PTB (a subset of PTBs with spontaneous labour) in 1,851 pregnancies resulting in live births from the Maternal-Infant Research on Environmental Chemicals Study (MIREC) using discrete time survival analysis. In addition, we investigated whether the risk of PTB was modified by plasma 25OHD concentration measured in the 1st trimester. RESULTS Six percent (n=117) of live births in the MIREC study were PTBs; 4% (n=89) were spontaneous PTBs. A 1 &amp;#x3bc;g/dL increase in blood lead concentrations during pregnancy was associated with increased risk of PTB (OR=1.5, 95% CI: 1.0, 2.3) and spontaneous PTB (OR=1.7, 95% CI: 1.1, 2.8). In stratified analysis, the risk of PTB (OR=2.7, 95% CI: 1.0, 7.2) and spontaneous PTB (OR=3.4, 95% CI: 1.1, 10.8) was higher in women with insufficient vitamin D concentrations (25OHD &amp;#x3c;50 nmol/L). However, a statistical interaction was not seen. Arsenic was associated with a higher risk of PTB (OR=1.1, 95% CI: 1.0, 1.2) and spontaneous PTB (OR=1.1, 95% CI: 1.0, 1.2) per µg/L, but these associations were not modified by vitamin D. CONCLUSIONS Low levels of lead and arsenic may increase the risk of PTB and spontaneous PTB; the association with lead was stronger in participants with insufficient plasma vitamin D. Replication of these findings is warranted.

Iodine Status Modifies the Association between Fluoride Exposure in Pregnancy and Preschool Boys' Intelligence.

In animal studies, the combination of in utero fluoride exposure and low iodine has greater negative effects on offspring learning and memory than either alone, but this has not been studied in children. We evaluated whether the maternal urinary iodine concentration (MUIC) modifies the association between maternal urinary fluoride (MUF) and boys’ and girls’ intelligence. We used data from 366 mother–child dyads in the Maternal–Infant Research on Environmental Chemicals Study. We corrected trimester-specific MUF and MUIC for creatinine, and averaged them to yield our exposure variables (MUFCRE, mg/g; MUICCRE, µg/g). We assessed children’s full-scale intelligence (FSIQ) at 3 to 4 years. Using multiple linear regression, we estimated a three-way interaction between MUFCRE, MUICCRE, and child sex on FSIQ, controlling for covariates. The MUICCRE by MUFCRE interaction was significant for boys (p = 0.042), but not girls (p = 0.190). For boys whose mothers had low iodine, a 0.5 mg/g increase in MUFCRE was associated with a 4.65-point lower FSIQ score (95% CI: −7.67, −1.62). For boys whose mothers had adequate iodine, a 0.5 mg/g increase in MUFCRE was associated with a 2.95-point lower FSIQ score (95% CI: −4.77, −1.13). These results suggest adequate iodine intake during pregnancy may minimize fluoride’s neurotoxicity in boys.

Ambient air pollution and inflammatory effects in a Canadian pregnancy cohort.

Epidemiologic studies have consistently reported associations between air pollution and pregnancy outcomes including preeclampsia and gestational diabetes. However, the biologic mechanisms underlying these relationships remain unclear as few studies have collected relevant biomarker data. We examined relationships between ambient PM2.5 and NO2 with markers of inflammation during pregnancy in a prospective cohort of Canadian women. We analyzed data from 1170 women enrolled in the Maternal-Infant Research on Environmental Chemicals study. Daily residential PM2.5 and NO2 exposures during pregnancy were estimated using satellite-based and land-use regression models and used to create 14-day and 30-day exposure windows before blood-draw. Inflammatory markers C-reactive protein, interleukin-6, interleukin-8, and tumor necrosis factor-α were measured in third trimester plasma samples. Multivariable linear regression was used to estimate associations for an interquartile range (IQR) increase in PM2.5 and NO2 and markers of inflammation, while adjusting for individual-level confounders. Fourteen-day (IQR: 6.85 µg/m3) and 30-day (IQR: 6.15 µg/m3) average PM2.5 exposures before blood-draw were positively associated with C-reactive protein after adjustment for covariates (24.6% [95% CI = 9.4, 41.9] and 17.4% [95% CI = 1.0, 35.0] increases, respectively). This association was found to be robust in several sensitivity analyses. Neither PM2.5 nor NO2 exposures were associated with interleukin-6, interleukin-8, or tumor necrosis factor-α. Exposure to ambient PM2.5 is positively associated with maternal inflammatory pathways in late pregnancy. This may contribute to positive associations between ambient PM2.5 and risk of adverse pregnancy outcomes.

Phthalate Toxicity in Rats and Its Relation to Testicular Dysgenesis Syndrome in Humans.

This work describes the relevance of toxicology studies of environmental chemicals, with a focus on phthalates, for a hypothesis that certain human male reproductive disorders and diseases have a common etiology of disturbance of normal development in utero. The "Testicular Dysgenesis Syndrome" hypothesis in humans has parallels in male reproductive tract abnormalities and microscopic lesions reported for phthalate toxicity in rats. Additionally, this work describes the histological findings of abnormal testicular development (testicular dysgenesis) in rats as compared to those in humans, as well as potential findings in rats at different ages, from the embryo to the adult.

Gestational Exposure to Toxicants and Autistic Behaviors using Bayesian Quantile Regression

BACKGROUND AND AIM: Autism Spectrum Disorder, which is characterized by impaired social communication and stereotypic behaviors, affects 1-2% of children. While prenatal exposure to toxicants has been associated with autistic behaviors, most studies have focused on shifts in mean behavior scores. METHODS: We used Bayesian quantile regression to assess the associations between log₂-transformed toxicant concentrations and autistic behaviors across the distribution of behaviors. We used data from the Maternal-Infant Research on Environmental Chemicals study, a pan-Canadian cohort (2008-2011). We measured metal, pesticide, polychlorinated biphenyl, phthalate, bisphenol-A, and triclosan concentrations in blood or urine samples collected during the first trimester of pregnancy. Autistic behaviors were assessed in 478 3-4-year-old children using the Social Responsiveness Scale (SRS), where higher scores denote more autistic-like behaviors. RESULTS:Lead, cadmium, and most phthalate metabolites were associated with mild increases in SRS scores at the 90th percentile of the SRS distribution. Manganese and some pesticides were associated with mild decreases in SRS scores at the 90th percentile of the SRS distribution. We identified several monotonic trends where associations increased in magnitude from the bottom to the top of the SRS distribution. CONCLUSIONS:These results suggest that Quantile regression can reveal nuanced relationships and should thus be more widely used by epidemiologists. KEYWORDS: Endocrine disrupting chemicals; Neurodevelopmental outcomes

Association Between Gestational Exposure to Toxicants and Autistic Behaviors Using Bayesian Quantile Regression.

Autism spectrum disorder, which is characterized by impaired social communication and stereotypic behaviors, affects 1%-2% of children. Although prenatal exposure to toxicants has been associated with autistic behaviors, most studies have been focused on shifts in mean behavior scores. We used Bayesian quantile regression to assess the associations between log2-transformed toxicant concentrations and autistic behaviors across the distribution of behaviors. We used data from the Maternal-Infant Research on Environmental Chemicals study, a pan-Canadian cohort (2008-2011). We measured metal, pesticide, polychlorinated biphenyl, phthalate, bisphenol-A, and triclosan concentrations in blood or urine samples collected during the first trimester of pregnancy. Using the Social Responsiveness Scale (SRS), in which higher scores denote more autistic-like behaviors, autistic behaviors were assessed in 478 children aged 3-4 years old. Lead, cadmium, and most phthalate metabolites were associated with mild increases in SRS scores at the 90th percentile of the SRS distribution. Manganese and some pesticides were associated with mild decreases in SRS scores at the 90th percentile of the SRS distribution. We identified several monotonic trends in which associations increased in magnitude from the bottom to the top of the SRS distribution. These results suggest that quantile regression can reveal nuanced relationships and, thus, should be more widely used by epidemiologists.

Performance of variable and function selection methods for estimating the nonlinear health effects of correlated chemical mixtures: A simulation study.

Statistical methods for identifying harmful chemicals in a correlated mixture often assume linearity in exposure-response relationships. Nonmonotonic relationships are increasingly recognized (eg, for endocrine-disrupting chemicals); however, the impact of nonmonotonicity on exposure selection has not been evaluated. In a simulation study, we assessed the performance of Bayesian kernel machine regression (BKMR), Bayesian additive regression trees (BART), Bayesian structured additive regression with spike-slab priors (BSTARSS), generalized additive models with double penalty (GAMDP) and thin plate shrinkage smoothers (GAMTS), multivariate adaptive regression splines (MARS), and lasso penalized regression. We simulated realistic exposure data based on pregnancy exposure to 17 phthalates and phenols in the US National Health and Nutrition Examination Survey using a multivariate copula. We simulated data sets of size N=250 and compared methods across 32 scenarios, varying by model size and sparsity, signal-to-noise ratio, correlation structure, and exposure-response relationship shapes. We compared methods in terms of their sensitivity, specificity, and estimation accuracy. In most scenarios, BKMR, BSTARSS, GAMDP, and GAMTS achieved moderate to high sensitivity (0.52-0.98) and specificity (0.21-0.99). BART and MARS achieved high specificity (≥0.90), but low sensitivity in low signal-to-noise ratio scenarios (0.20-0.51). Lasso was highly sensitive (0.71-0.99), except for quadratic relationships (≤0.27). Penalized regression methods that assume linearity, such as lasso, may not be suitable for studies of environmental chemicals hypothesized to have nonmonotonic relationships with outcomes. Instead, BKMR, BSTARSS, GAMDP, and GAMTS are attractive methods for flexibly estimating the shapes of exposure-response relationships and selecting among correlated exposures.

Environmental risk factors for endometriosis: A critical evaluation of studies and recommendations from the epidemiologic perspective.

Recent studies of environmental chemicals and endometriosis were critically evaluated from the epidemiologic perspective to identify aspects of study design and analyses that may contribute to discrepant results across studies. Of the 29 studies reviewed, 12 studies used new approaches to population-based sampling. The remaining studies were conducted primarily among patients undergoing pelvic surgery; controls may not represent the exposure experience of the underlying study base, resulting in biased estimates of associations. Most studies used biologic specimens collected near diagnosis and varied in analytic approaches to minimize bias. Few studies investigated ovarian, deep-infiltrating, and peritoneal endometriosis presentations separately. Recommendations to move the field forward include: (1) control selection from a defined study base, (2) exposure characterization during the etiologically-relevant window, (3) employment of best practices to minimize bias in analyses, and (4) separate consideration of endometriosis presentations that may be etiologically-distinct entities.

GC-MS Analysis of Phthalates and Di-(2-thylhexyl) Adipate in Canadian Human Milk for Exposure Assessment of Infant Population.

Although more information has become available on the occurrence of phthalates and di(2-ethylhexyl) adipate (DEHA) in foods including cow's milk, information on their presence in human milk, the important and recommended sole diet for infants up to six months of age, is very limited, especially for DEHA. To develop a GC-MS method for simultaneous analysis of DEHA and phthalates in human milk samples and generate occurrence data for exposure assessment. Human milk samples were extracted with acetonitrile followed by dispersive solid-phase extraction and GC-MS analysis. Among the 305 human milk samples collected from the Canadian Maternal-Infant Research on Environmental Chemicals Study, some phthalates (DHxP, BBzP, and DOP) were not detected in any of the samples, while DEHA and the other phthalates (DMP, DEP, DBP, DiBP, and DEHP) were detected at low frequencies with levels from 30.4-237 ng/g in up to 31 of the 305 human milk samples. In general, DEHA and phthalates were detected at low frequencies and low levels in the 305 human milk samples. A GC-MS method based on dispersive solid phase extraction was developed for analysis of DEHA and eight phthalates in 305 human milk samples for exposure assessment.

Prenatal exposure to legacy contaminants and visual acuity in Canadian infants: a maternal-infant research on environmental chemicals study (MIREC-ID)

BackgroundPrenatal exposure to environmental contaminants can have deleterious effects on child development. While psychomotor, cognitive and behavioural outcomes have been investigated in relation to chronic exposure, the associations with visual functions remains unclear. The present study’s aim was to assess the associations of prenatal exposure to legacy persistent organic pollutants and heavy metals with visual acuity in Canadian infants. The potential protective effects of selenium against mercury toxicity were also examined.MethodsParticipants (mean corrected age = 6.6 months) were part of the Maternal-Infant Research on Environmental Chemicals (MIREC) study. Concentrations of polychlorinated biphenyls (PCBs), polybrominated diphenyl ethers (PBDEs), lead and mercury were measured in maternal blood during pregnancy, as well as in the cord blood. The Teller acuity card test (TAC) (n = 429) and the visual evoked potentials in a sub-group (n = 63) were used to estimate behavioural and electrophysiological visual acuity, respectively. Multivariable linear regression models were used to investigate the relationship between exposure to each contaminant and visual acuity measures, while controlling for potential confounders. Breastmilk selenium, which was available for about half of the TAC and VEP samples, was also taken into account in the mercury models as exploratory analyses.ResultsWe observed no significant associations between exposure to any contaminants and TAC. Analyses revealed a negative trend (p values < 0.1) between cord blood lead and mercury and electrophysiological visual acuity, whereas PCB and PBDE showed no association. When adding breastmilk selenium concentration to the mercury models, this association became statistically significant for cord concentrations (β = − 3.41, 95% CI = − 5.96,-0.86), but also for blood levels at 1st and 3rd trimesters of pregnancy (β = − 3.29, 95% CI = − 5.69,-0.88). However, further regression models suggested that this change in estimates might not be due to adjustment for selenium, but instead to a change in the study sample.ConclusionsOur results suggest that subtle, but detectable alterations of infant electrophysiological visual acuity can be identified in a population prenatally exposed to low mercury concentrations. Compared to behavioural visual acuity testing, electrophysiological assessment may more sensitive in detecting visual neurotoxicity in relation with prenatal exposure to mercury.

Correlates of plasma concentrations of brominated flame retardants in a cohort of U.S. Black women residing in the Detroit, Michigan metropolitan area

BackgroundPolybrominated diphenyl ethers (PBDEs) and polybrominated biphenyls (PBBs) are brominated flame retardant chemicals detectable in the environment and U.S. population, and are associated with adverse health outcomes over the life course. Correlates of these organic pollutants are understudied among U.S. Black women. MethodsUsing baseline data from a prospective cohort study of U.S. Black women aged 23–35 years from the Detroit area of Michigan (2010−2012), we examined correlates of PBDEs and PBB-153. Non-fasting blood samples were collected from 742 participants at enrollment, a subset of women selected for a case-cohort study of environmental chemicals. Data on socio-demographics, behaviors, diet, medical history, and early-life exposures were collected via self-administered questionnaires, telephone interviews, and in-person clinic visits. We fit linear regression models to calculate percent differences and 95% confidence intervals in lipid adjusted plasma concentrations of 11 individual PBDE congeners and PBB-153 for each baseline predictor. ResultsIn models adjusted for all other correlates, a 5-year increase in age was inversely associated with most PBDE congeners (% differences ranged from 6 to 15% lower), and was positively associated with PBB-153 (52% higher). A 5-kg/m2 increase in BMI was inversely associated with PBDE-153 and PBB-153 (16% lower for both), and 6% higher for PBDE-28. Compared with having never been breastfed in infancy, ≥3 months of breastfeeding in infancy was associated with 69% higher PBB-153 concentrations. Lower education, current smoking, and heavy alcohol use were associated with higher plasma concentrations of most flame retardants. Diet was not an important predictor. ConclusionImportant correlates for elevated body burdens of PBB-153 were increasing age and a history of having been breastfed in infancy. Education, smoking, and heavy alcohol use were important predictors of elevated body burdens of most flame retardants. This study fills an important gap in the environmental health literature by focusing on an understudied population.

Performance of variable selection methods for estimating the non-linear health effects of correlated chemical mixtures

OPS 05: Statistical methods to analyze mixtures, Room 114, Floor 1, August 27, 2019, 1:30 PM - 3:00 PM Background/Aim: Statistical methods for identifying harmful chemicals in a correlated mixture often assume linearity in exposure–response relationships. Non-monotonic relationships are biologically plausible (e.g., endocrine-disrupting chemicals); however, the impact of non-monotonicity on the performance of variable selection methods has not been evaluated. In a simulation study, we assessed the performance of three methods for the identification of important mixture components when exposure-response relationships are expected to be non-linear, including Bayesian kernel machine regression (BKMR), Bayesian additive regression trees (BART), and Bayesian structured additive regression with spike–slab priors (BSTARSS). We compared these methods to lasso penalised regression assuming linearity. Methods: We used data on exposure to phthalates and phenols in pregnant women from the U.S. National Health and Nutrition Examination Survey to simulate realistic exposure data using a multivariate copula, which allowed us to vary the correlation structure while preserving the observed marginal distributions. We simulated datasets of size N=250 and compared methods across 32 scenarios, varying by model size and sparsity, signal-to-noise ratio, exposure correlation structure, and shape of exposure–response relationships (including linear, S-shaped, and both symmetric and asymmetric inverse-U-shaped relationships). We compared the performance of methods in terms of their sensitivity, specificity, and estimation accuracy. Results: BKMR and BSTARSS achieved moderate to high specificity and sensitivity in most scenarios. BART achieved high specificity (>0.96), but low to moderate sensitivity (0.12–0.66). Lasso was highly sensitive (0.75–0.99), except when exposure–response relationships were symmetric inverse-U-shaped (<0.2). Performance was affected by changes in the signal-to-noise ratio but not substantially by the correlation structure. Conclusions: Penalised regression methods assuming linearity, such as lasso, may not be suitable in studies of environmental chemicals hypothesised to have non-monotonic relationships with outcomes. Instead, BKMR and BSTARSS may be used to flexibly estimate the shapes of exposure–response relationships and to select among correlated exposures in small sample size studies.

Perchlorate in human milk samples from the maternal-infant research on environmental chemicals study (MIREC)

ABSTRACTPerchlorate is a low molecular weight highly soluble anion. It occurs naturally in the environment, primarily near potash deposits and in arid regions. The determination of perchlorate in human milk is of interest in vulnerable populations such as infants and pregnant women. In this study, a sensitive and selective isotope dilution ion chromatography/tandem mass spectrometry (ID IC-MS/MS) method was developed and validated for the determination of perchlorate in human milk samples collected from the Maternal-Infant Research on Environmental Chemicals (MIREC) Study. The limit of detection (LOD) was 0.27 µg·kg−1 for human milk. A total of 439 human milk samples were analysed with measurable levels of perchlorate in most of the milk samples, and the mean value was 7.62 ± 32.7 µg·kg−1. This project provided important information related to perchlorate levels in human milk collected across Canada and the extent to which pregnant women and their infants may be exposed to perchlorate. A dietary exposure assessment was also conducted in infants based on the measured values in human milk. The mean perchlorate probable daily intakes (PDIs) for infants consuming human milk were 0.31 ± 0.07 μg/kg bw/day for infants under 1 year and 0.17 ± 0.10 μg/kg bw/day for infants between 1 and 3 years old. None of the estimates exceeded the FAO/WHO provisional maximum tolerable daily intake (PMTDI) of 10 μg/kg bw/day.