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Studies characterizing associations between phenols, phthalates and thyroid hormones during pregnancy produce inconsistent results. This divergence may be partly attributable to false positives due to multiple comparison testing of large numbers of chemicals, and measurement error as studies rely on small numbers of biospecimens despite high intra-individual variability in urinary chemical metabolite concentrations.This study employsA two-tiered approach was implemented:The ToxCast/Tox21 screening reduced the chemical set from 16 to 13 and the associated number of statistical comparisons by 19%. Parabens were negatively associated with free triiodothyronine (T3) and the T3/T4 (total thyroxine) ratio. Monobenzyl phthalate was positively associated with total T4 and negatively with the T3/T4 ratio. Effect modification by iodine status was detected for several compounds (among themFor these chemicals, screening for compounds with an increased likelihood for thyroid-related effects and relying on repeated urine samples to assess exposures improved the overall performance of multichemical analyses of thyroid disruption. This approach may improve future evaluations of human data for the thyroid pathway with implication for fetal health and may serve as a model for evaluating other toxicity outcomes. https://doi.org/10.1289/EHP10239.

International audience; Background and objectives: Studies focusing on the neurodevelopmental effects of phthalates seldom consider exposure during infancy, a critical period for brain development. Most rely on parent-completed questionnaires to assess child neurodevelopment, which may be subject to reporting error. We studied the associations between prenatal and infancy exposure to phthalates and objective measures of neurodevelopment at the age of two. Methods: We relied on 151 mother-child pairs from the SEPAGES mother-child cohort. Women were asked to collect three spot urine samples per day over seven consecutive days during the second (median: 18.0 gestational weeks) and third (median: 34.2 gestational weeks) trimesters of pregnancy. They then collected one urine sample per day over seven consecutive days from their infants around the age of 12 months. Metabolites of phthalates and non-phthalate plasticizers were measured in within-subject and within-period pools of repeated urine samples. Eye tracking tasks were performed at two years allowing to compute four indicators linked with cognitive development and visual behavior: mean fixation duration, novelty preference, percent time spent looking at the eyes and mean reaction time. Results: Pre-natal exposure to monobenzyl phthalate at the second and third trimesters was associated with shorter fixation durations. In models allowing for interaction with child sex, these associations were only observed among girls. Exposure to di(2-ethylhexyl) phthalate at the third but not the second trimester was associated with increased time spent looking at a novel face and eyes. We observed faster reaction times and decreased time spent looking at the eyes in a face recognition task, with increased post-natal exposure to monoethyl, mono-iso-butyl and mono-n-butyl phthalates. Discussion: Relying on improved exposure assessment, we highlighted associations of pre-and post-natal exposure to phthalates with indicators derived from eye tracking tasks, mainly in girls. Some of these indicators have been affected in individuals with neurodevelopmental disorders.

International audience; Background: Some synthetic phenols alter pathways involved in fetal development. Despite their high within-subject temporal variability, earlier studies relied on spot urine samples to assess pregnancy exposure. In this study, we examined associations between prenatal phenol exposure and fetal growth. Methods: We measured concentrations of two bisphenols, four parabens, benzophenone-3, and triclosan in 478 pregnant women in two weekly pools of 21 samples each, collected at 18 and 34 gestational weeks. We used adjusted linear regressions to study associations between phenol concentrations and growth outcomes assessed twice during pregnancy and at birth. Results: Benzophenone-3 was positively associated with all ultrasound growth parameters in at least one time point, in males but not females. In females, butylparaben was negatively associated with third-trimester abdominal circumference and weight at birth. We observed isolated associations for triclosan (negative) and for methylparaben and bisphenol S (positive) and late pregnancy fetal growth. Conclusions: Our results suggest associations between prenatal exposure to phenols and fetal growth. Benzophenone-3 was the exposure most consistently (positively) associated across all growth parameters.

Background: Prenatal exposure to per- and polyfluoroalkyl substances (PFAS) may be a risk factor for neurodevelopmental deficits and disorders, but evidence is inconsistent. Objectives: We investigated whether prenatal exposure to PFAS were associated with childhood diagnosis of attention-deficit/hyperactivity disorder (ADHD) or autism spectrum disorder (ASD). Methods: This study was based on the Norwegian Mother, Father and Child Cohort Study and included n = 821 ADHD cases, n = 400 ASD cases and n = 980 controls. Diagnostic cases were identified by linkage with the Norwegian Patient Registry. In addition, we used data from the Medical Birth Registry of Norway. The study included the following PFAS measured in maternal plasma sampled mid-pregnancy: Perfluorooctanoic acid (PFOA), perfluorononanoic acid (PFNA), perfluorodecanoic acid (PFDA), perfluoroundecanoic acid (PFUnDA), perfluorohexane sulfonate (PFHxS), perfluoroheptanesulfonic acid (PFHpS), and perfluorooctane sulfonate (PFOS). Relationships between individual PFAS and ADHD or ASD diagnoses were examined using multivariable adjusted logistic regression models. We also tested for possible non-linear exposure-outcome associations. Further, we investigated the PFAS mixture associations with ASD and ADHD diagnoses using a quantile-based g-computation approach. Results: Odds of ASD was significantly elevated in PFOA quartile 2 [OR = 1.71 (95% CI: 1.20, 2.45)] compared to quartile 1, and PFOA appeared to have a non-linear, inverted U-shaped dose-response relationship with ASD. PFOA was also associated with increased odds of ADHD, mainly in quartile 2 [OR = 1.54 (95% CI: 1.16, 2.04)] compared to quartile 1, and displayed a non-linear relationship in the restricted cubic spline model. Several PFAS (PFUnDA, PFDA, and PFOS) were inversely associated with odds of ADHD and/or ASD. Some of the associations were modified by child sex and maternal education. The overall PFAS mixture was inversely associated with ASD [OR = 0.76 (95% CI: 0.64, 0.90)] as well as the carboxylate mixture [OR = 0.79 (95% CI: 0.68, 0.93)] and the sulfonate mixture [OR = 0.84 (95% CI: 0.73, 0.96)]. Conclusion: Prenatal exposure to PFOA was associated with increased risk of ASD and ADHD in children. For some PFAS, as well as their mixtures, there were inverse associations with ASD and/or ADHD. However, the inverse associations reported herein should not be interpreted as protective effects, but rather that there could be some unresolved confounding for these relationships. The epidemiologic literature linking PFAS exposures with neurodevelopmental outcomes is still inconclusive, suggesting the need for more research to elucidate the neurotoxicological potential of PFAS during early development.

For non-persistent chemicals such as phthalates, a single spot urine sample only reflects exposure in the past few hours. Collecting repeated urine samples for each participant over windows of sensitivity is expected to improve exposure characterization but has rarely been done. We aimed to rely on within-subject pools of repeated urine samples to assess phthalate exposure during pregnancy and infancy. Women of the French SEPAGES mother-child cohort were asked to collect three urine samples per day over seven consecutive days, twice during their pregnancy (approximatively second (T2) and third (T3) trimesters). For their infants they also collected one sample per day during a week at two (M2) and twelve months (M12). Samples were pooled (within-subject, within-period) prior to phthalate and DINCH metabolite concentrations assessment. Number of pooled samples assayed was 477, 456, 152 and 100 for T2, T3, M2 and M12, respectively. All metabolites were detected in more than 95% of the pooled samples except for the two DINCH metabolites (oh- and oxo-MINCH), MMCHP and oh-MPHP at M2 for which detection frequencies ranged between 64% and 88%. Maternal concentrations of MiBP, MBzP, DEHP metabolites and oxo-MiNP decreased between 2014 and 2017, whereas concentrations of oh-MiNP and the two DINCH metabolites increased (Mann-Kendall p-values, Graphical abstract Image 1, Highlights • Repeated urine samples were collected and pooled within-subject, within period. • Metabolites of phthalates and DINCH were measured in pooled samples. • Frequencies of detection were overall high. • Pregnancy concentrations of MiBP, MBzP, DEHP and oxo-MINP decreased with time. • Pregnancy concentrations of oh-MiNP and DINCH metabolites increased with time., Relying on a recent cohort (2014–2017) with repeated urine samples collected during pregnancy and infancy, we showed that exposure to phthalates and DINCH is still widespread in the general population.

Persistent organic pollutants (POPs) can reach the fetal brain and contribute to developmental neurotoxicity. To explore the distribution of POPs to the fetal brain, we exposed chicken embryos to a POP mixture, containing 29 different compounds with concentrations based on blood levels measured in the Scandinavian human population. The mixture was injected into the allantois at embryonic day 13 (E13), aiming at a theoretical concentration of 10 times human blood levels. POPs concentrations in the brain were measured at 0.5, 1, 2, 4, 6, 24, 48, and 72 h after administration. Twenty-seven of the individual compounds were detected during at least one of the time-points analyzed. Generally, the concentrations of most of the measured compounds were within the order of magnitude of those reported in human brain samples. Differences in the speed of distribution to the brain were observed between the per- and polyfluoroalkyl substances (PFASs), which have protein binding potential, and the lipophilic polychlorinated biphenyls (PCBs), organochlorine pesticides (OCPs) and brominated flame retardants (BFRs). Based on pharmacokinetic modeling, PFASs were best described by a one compartment model. PFASs displayed relatively slow elimination (Kel) and persisted at high levels in the brain. Lipophilic OCPs and PCBs could be fitted to a 2-compartment model. These showed high levels in the brain relative to the dose administrated as calculated by area under the curve (AUC)/Dose. Altogether, our study showed that chicken is a relevant model to explore the distribution of POPs into the developing brain at concentrations which are relevant for humans.

Background: Recent studies have suggested the involvement of several endocrine disruptors, including synthetic phenols and phthalates, in the development of infant behavioural disorders. These stud...

The objective of the present study was to investigate recent concentrations of perfluoroalkyl substances (PFASs) in white whales (Delphinapterus leucas) from Svalbard and compare them to concentrations found in white whales sampled from that same area 15 years ago. Plasma collected from live-captured white whales from two time periods (2013–2014, n = 9, and 1996–2001, n = 11) were analysed for 19 different PFASs. The 11 PFASs detected included seven C8–C14 perfluoroalkyl carboxylates (PFCAs) and three C6–C8 perfluoroalkyl sulfonates (PFSAs) as well as perfluorooctane sulfonamide (FOSA). Recent plasma concentrations (2013–2014) of the dominant PFAS in white whales, perfluorooctane sulfonate (PFOS; geometric mean = 22.8 ng/mL), was close to an order of magnitude lower than reported in polar bears (Ursus maritimus) from Svalbard. PFOS concentrations in white whales were about half the concentrations in harbour (Phoca vitulina) and ringed (Pusa hispida) seals, similar to hooded seals (Cystophora cristata) and higher than in walruses (Odobenus rosmarus) from that same area. From 1996 to 2001 to 2013–2014, plasma concentrations of PFOS decreased by 44%, whereas four C9-12 PFCAs and total PFCAs increased by 35–141%. These results follow a similar trend to what has been reported in other studies of Arctic marine mammals from Svalbard. The most dramatic change has been the decline of PFOS concentrations since 2000, corresponding to the production phase-out of PFOS and related compounds in many countries around the year 2000 and a global restriction on these substances in 2009. Still, the continued dominance of PFOS in white whales, and increasing concentration trends for several PFCAs, even though exposure is relatively low, calls for continued monitoring of concentrations of both PFCAs and PFSAs and investigation of biological effects. This article is available under the Creative Commons CC-BY-NC-ND license and permits non-commercial use of the work as published, without adaptation or alteration provided the work is fully attributed.

Objective: Because oral contraceptives (OC) tends to lessen menstrual fluid loss – a route of excretion for perfluoroalkyl substances (PFASs) – we hypothesized that such use would be positively associated with PFAS concentrations. Methods: This analysis was based on the Norwegian Mother and Child Cohort (MoBa) study. We included 1090 women from two previous substudies of women enrolled from 2003 to 2007. Characteristics of OC use were obtained at baseline: use in the past 12months, duration and recency of use, age at first use. We examined log-transformed plasma concentrations of seven PFASs (perfluorooctanoic acid (PFOA), perfluorononanoic acid (PFNA), perfluorodecanoic acid (PFDA), perfluoroundecanoic acid (PFUnDA), perfluorohexane sulfonate (PFHxS), perfluoroheptane sulfonate (PFHpS), and perfluorooctane sulfonate (PFOS)). Linear regression analyses, adjusted for maternal age, menstrual cycle length, parity, and education, were used to examine whether OC use characteristics were determinants of PFAS concentrations. Results: Except for PFDA and PFUnDA, women who used OCs in the 12months preceding the baseline interview had 12.9–35.7% higher PFAS concentrations than never OC users. To a lesser extent, past OC use was positively associated with PFASs (estimates ranged from 7.2–32.1%). Compared with never users, using OCs for 10 or more years was associated with increased PFAS concentrations, except for PFDA and PFUnDA (estimates for other PFASs ranged from 18.9–46.2%). We observed little effect of age at first OC use. Conclusions: This analysis shows that characteristics of OC use, and duration of use in particular, may be important considerations when investigating relationships between women's reproductive outcomes and PFASs. Keywords: MoBa, The Norwegian Mother and Child Cohort study, Perfluoroalkyl substances, PFOS, PFOA, Oral contraceptives

Exposure to phthalates has been associated with reproductive and developmental toxicity. Data on levels of these compounds in the Norwegian population is limited. In this study, urine samples were collected from 48 mothers and their children in two counties in Norway. Eleven different phthalate metabolites originating from six commonly used phthalates in consumer products were determined. Concentrations of phthalate metabolites were significantly higher in children compared to mothers except for mono-ethyl phthalate (MEP). The mothers provided several urine samples during 24hours (h) and diurnal variation showed that the concentrations in the morning urine samples (24-8h) were significantly higher than at other time-periods for most of the phthalate metabolites. Intraclass correlation coefficients (ICCs) for 24-hour time-period were in the range of 0.49-0.81. These moderate to high ICCs indicate that one spot urine sample can be used to estimate the exposure to phthalates. Since a significant effect of time of day was observed, it is still advisable to standardize the collection time point to reduce the variation. For the mothers, the use of personal care products (PCPs) were less associated with morning urine samples than early day (8-12h) and evening (16-24h) urine samples. The use of perfume and hair products were positively associated with the urinary concentrations of low molecular weight phthalates. Use of shower soap and shampoo were positively associated with urinary concentration of di(2-ethylhexyl) phthalate (DEHP) metabolites. For children, face cream use was positively associated with phthalate metabolites in the morning samples, and hand soap use was negatively associated with concentration of urinary DEHP metabolites in afternoon/evening samples. Since different PCPs were associated with the urinary phthalate metabolites in different time-periods during a day, more than one spot urine sample might be required to study associations between urinary phthalate metabolites and the use of PCPs.

Background: Exposure to multiple chemicals occurs daily through several routes; diet, inhalation and dermal contact. Real-life exposure assessment is needed to understand the risk. Therefore, a human biomonitoring (BM) study was performed to examine the plausibility of source-to-dose calculations for chemical mixtures in the Horizon 2020 EuroMix project. Objectives: To provide a detailed description of the design of the EuroMix BM study, and to present the initial results for urinary phenols and phthalates and to describe their exposure determinants from foods and personal care products (PCPs). Method: Adults (44 males and 100 females) kept detailed diaries on their food consumption, PCP use and handling of cash receipts. Urine samples were collected over the same 24-hour period. Urinary levels of four parabens, five bisphenols, oxybenzone/benzophenone-3 (OXBE), triclosan (TCS), triclocarban (TCC) and metabolites of eight phthalates and 1,2-cyclohexane dicarboxylic acid diisononyl ester (DINCH) were analysed by ultra-high-performance liquid chromatography and tandem mass spectrometry. Multivariable linear regressions were performed between PCPs/food categories and each dependent chemical variable separately, and were only sex-stratified when an interactions between sex and the independent variable was significant. Results: The detection rate for the metabolites of phthalates and DINCH, and bisphenol A (BPA) and TCS in urine was 88–100%, while bisphenol S (BPS) and bisphenol F (BPF) were only found in 29% and 4% of the urine samples, respectively. Bisphenol B (BPB), bisphenol AF (BPAF) and TCC were not detected. Food groups associated with phenol exposure were meat, bread, beverages and butter and oil. Food determinants for phthalate exposure were sweets, butter and oil, fruit and berries and other foods. The only positive association between the use of PCPs and phenols was found between BPA and lip gloss/balm. Phthalate exposure was associated with the use of shower gel, hand cream (females), toothpaste, anti-wrinkle cream (females) and shaving products (males). Conclusion: The participants in the EuroMix BM study were exposed to a mixture of phenols and phthalates. A variety of food categories and PCPs were found to be possible sources of these chemicals. This indicates a complex pattern of exposure to numerous chemicals from multiple sources, depending on individual diet and PCP preferences. Keywords: Contaminants, Chemicals, Phenols, Phthalate, Bisphenol, Paraben, Biomonitoring, Food, Personal care products, 24-hour urine

High exposure to perfluoroalkyl substances (PFASs) has been associated with adverse health effects in children. PFASs exposure pathways of toddlers might differ from those of infants and adults, and the investigations on determinants of PFASs exposure in early childhood are scarce. Our aims were to examine the PFAS blood concentrations in Norwegian toddlers and to assess their relationship with maternal PFAS concentrations in pregnancy and breastfeeding duration. We determined PFAS concentrations in 112 plasma samples of 3-year-old children collected at 2010–2011 and 99 maternal serum samples collected around delivery at 2007–2008. PFAS concentrations in children were regressed on duration of breastfeeding, and the effect modification by maternal prenatal PFAS concentrations was examined in 55 mother-child pairs. Six PFASs were quantifiable in >50% of both maternal and children samples. Positive and significant correlations ranging between 0.50 and 0.66 were found between maternal and child concentrations of the same PFAS congeners. Nevertheless, toddlers had higher total PFAS blood concentrations than their mothers, due to higher concentrations of PFOA, PFNA and PFHxS. Every month of breastfeeding was associated with an increase of 3.3% (95% Confidence Intervals (CI): 0.8–5.8) for PFOS, 4.7% (95%CI: 2.8–6.6) for PFOA and 6.1% (95% CI: 2.6–9.7) for PFHpS in toddlers' plasma and a dose-response association was found, after adjustment for confounders. However, PFNA and PFUnDA concentrations in children were not associated with either maternal concentrations or breastfeeding duration. Our findings suggest that transplacental transfer, prenatally, and breastfeeding, postanatally, are among the main determinants of PFOS, PFOA, PFHxS and PFHpS concentrations in toddlers, while that was not the case for PFNA and PFUnDA. Nevertheless, due to the small number of mother child-pairs in our study, our results should be interpreted with caution. Keywords: PFOA, PFNA, Children, Toddlers, Prenatal exposure, Breastfeeding

BACKGROUND A previous study reported a negative association between perfluorooctane sulfonamide (PFOSA) concentrations and fecundability. METHODS We examined this association among women enrolled in the Norwegian Mother and Child Cohort Study (MoBa), in 2003-2004. This analysis was restricted to 451 primiparous women to avoid bias due to previous pregnancy. Self-reported time-to-pregnancy (TTP) and plasma were obtained around 18 weeks of gestation. Approximately half of the women had measurable PFOSA levels; missing values were multiply imputed. We used the logistic analogue of discrete-time survival analysis to examine the adjusted association between PFOSA, other perfluoroalkyl substances, and TTP. RESULTS The median-measured PFOSA concentration was 0.03 ng/ml (interquartile range = 0.02, 0.07). The age and body mass index-adjusted association between an interquartile distance increase in PFOSA and TTP was 0.91 (95% confidence interval = 0.71, 1.17). Imputation of missing PFOSA resulted in similar estimates. No association was observed with other perfluoroalkyl substances. CONCLUSION Based on a weakly decreased fecundability odds ratio, we found only limited support for an association between plasma PFOSA concentrations and TTP among primiparous women. See Video Abstract at http://links.lww.com/EDE/B79.

Background: Exposure to environmental phenols including parabens, bisphenols (BPs), oxybenzone/benzophenone-3 (BP-3) and triclosan (TCS) is ubiquitous. Due to evidence of their estrogenic activity, they have been considered as chemicals of concern. The exposure of the Norwegian population to these compounds is presently unknown. Aims: To measure urinary levels of twelve different environmental phenols including four emerging bisphenols: S, F, B and AF (abbreviated as BPS, BPF, BPB and BPAF, respectively) in a healthy Norwegian population. We have calculated short-term variability, estimated daily intakes and investigated important determinants of exposure. Methods: Urine samples were collected from mothers (n = 48) and their children (n = 56) during spring/summer 2012 in two counties in Norway. Results: Six environmental phenols namely methyl, ethyl and propyl paraben, BPA, BP-3 and TCS were detected in almost 100% of the urine samples. Among the emerging bisphenols, BPS was detected most frequently in the urine samples (42–48%) followed by BPF (4–15%). Parabens were positively and significantly correlated to each other in both mothers and children. Levels of parabens and BP-3 were higher in mothers compared to children. All mothers and children had lower estimated daily intakes (back calculated from the urinary concentrations) of parabens and BPA than the respective acceptable and tolerable daily intakes (ADIs and TDIs) established by the European Food Safety Authority (EFSA). Observed intraclass correlation coefficients (ICCs) indicated moderate to high reliability of spot urine measurements for all the environmental phenols (ICCs: 0.70–0.97). Use of hair products, deodorants, face and hand creams were significantly associated with higher urinary levels of parabens. Conclusions: Occurrence of environmental phenols in healthy Norwegian women and children is abundant. Among emerging bisphenols, there is widespread exposure to BPS. A single spot urine sample can be used for estimating short-term exposures of environmental phenols. Urinary levels of parabens were associated with use of PCPs. Keywords: Phenol, urine, Mass spectrometry, Personal care products, Diurnal variability, ICC

Introduction Perfluoroalkyl substances (PFASs) are fluorinated organic compounds that have been used in a variety of industrial and consumer applications. Menstruation is implicated as a possible route of elimination for PFASs in women. The overall purpose of this study was to examine menstrual cycle characteristics as determinants of plasma PFAS concentrations in women. Methods Our study sample consisted of 1977 pregnant women from the Norwegian Mother and Child Cohort (MoBa) study. The women were asked about menstrual cycle regularity in the year before the pregnancy and typical menstrual cycle length as well as other demographic and reproductive characteristics in a questionnaire completed during the pregnancy. Blood samples were collected around 17–18 weeks gestation and PFAS concentrations were measured in plasma. We examined the association between menstrual cycle characteristics and seven PFASs (perfluorooctanoic acid (PFOA), perfluorononanoic acid (PFNA), perfluorodecanoic acid (PFDA), perfluoroundecanoic acid (PFUnDA), perfluorohexane sulfonate (PFHxS), perfluoroheptane sulfonate (PFHpS), and perfluorooctane sulfonate (PFOS)) using multiple linear regression, adjusted for age, pre-pregnancy body mass index, smoking, education, income, parity, oral contraceptive use, inter-pregnancy interval, and breastfeeding duration. Results Irregular cycles were not associated with PFAS concentrations. Overall, we found no evidence of associations between menstrual cycle length and PFAS concentrations. In subgroup analyses we found some evidence, among parous women, of decreased PFHpS and PFOS with short menstrual cycles; we also found, among recent OC users (in the 12 months before the questionnaire) increased PFNA and PFUnDA with long cycle length. Limitations of our study include misclassification of menstrual cycle characteristics, small sample sizes in the sub-group analyses, and a lack of information on duration and volume of menses. Conclusions In the entire study sample, we found little evidence of menstrual cycle characteristics as determinants of PFAS concentrations. However, we observed some associations between cycle length and PFAS concentrations with some select PFAS compounds in subgroup analyses.

Background: Perfluoroalkyl substances (PFASs) are widespread and persistent environmental pollutants. Previous studies, primarily among non-pregnant individuals, suggest positive associations between PFAS levels and certain blood lipids. If there is a causal link between PFAS concentrations and elevated lipids during pregnancy, this may suggest a mechanism by which PFAS exposure leads to certain adverse pregnancy outcomes, including preeclampsia. Methods: This cross-sectional analysis included 891 pregnant women enrolled in the Norwegian Mother and Child (MoBa) Cohort Study in 2003–2004. Non-fasting plasma samples were obtained at mid-pregnancy and analyzed for nineteen PFASs. Total cholesterol, high-density lipoprotein (HDL) cholesterol, low-density lipoprotein cholesterol, and triglycerides were measured in plasma. Linear regression was used to quantify associations between each PFAS exposure and each lipid outcome. A multiple PFAS model was also fitted. Results: Seven PFASs were quantifiable in >50% of samples. Perfluorooctane sulfonate (PFOS) concentration was associated with total cholesterol, which increased 4.2 mg/dL per inter-quartile shift (95% CI = 0.8, 7.7) in adjusted models. Five of the seven PFASs studied were positively associated with HDL cholesterol, and all seven had elevated HDL associated with the highest quartile of exposure. Perfluoroundecanoic acid showed the strongest association with HDL: HDL increased 3.7 mg/dL per inter-quartile shift (95% CI = 2.5, 4.9). Conclusion: Plasma concentrations of PFASs were positively associated with HDL cholesterol, and PFOS was positively associated with total cholesterol in this sample of pregnant Norwegian women. While elevated HDL is not an adverse outcome per se, elevated total cholesterol associated with PFASs during pregnancy could be of concern if causal. Keywords: The Norwegian Mother and Child Cohort Study, MoBa, Perfluoroalkyl substances, Perfluorooctanoic acid, Perfluorooctane sulfonate

Background: Perfluoroalkyl substances (PFASs) are widespread pollutants that have been associated with adverse health effects although not on a consistent basis. Diet has been considered the main source of exposure. The aim of the present study was to identify determinants of four plasma PFASs in pregnant Norwegian women. Methods: This study is based in the Norwegian Mother and Child Cohort Study (MoBa) conducted by the Norwegian Institute of Public Health. Our sample included 487 women who enrolled in MoBa from 2003 to 2004. A questionnaire regarding sociodemographic, medical, and reproductive history was completed at 17 weeks of gestation and a dietary questionnaire was completed at 22 weeks of gestation. Maternal plasma samples were obtained around 17 weeks of gestation. Plasma concentrations of four PFASs (perfluorooctane sulfonate (PFOS), perfluorooctanoate (PFOA), perfluorohexane sulfonate (PFHxS), and perfluorononanoate (PFNA)) were examined in relation to demographic, lifestyle, dietary, and pregnancy-related covariates. Predictors were identified by optimizing multiple linear regression models using Akaike's information criterion (AIC). Results: Parity was the determinant with the largest influence on plasma PFAS concentrations, with r2 between 0.09 and 0.32 in simple regression models. In optimal multivariate models, when compared to nulliparous women, parous women had 46%, 70%, 19%, and 62% lower concentrations of PFOS, PFOA, PFHxS, and PFNA respectively (p

BACKGROUND: Perfluorooctane sulfonate (PFOS) and perfluorooctanoic acid (PFOA) have consistently been associated with higher cholesterol levels in cross sectional studies. Concerns have, however, been raised about potential confounding by diet and clinical relevance.OBJECTIVE: To examine the association between concentrations of PFOS and PFOA and total cholesterol in serum during pregnancy taking into considerations confounding by diet.METHODS: 854 Danish women who gave birth in 1988-89 and provided a blood sample and reported their diet in week 30 of gestation.RESULTS: Mean serum PFOS, PFOA and total cholesterol concentrations were 22.3ng/mL, 4.1ng/mL and 7.3mmol/L, respectively. Maternal diet was a significant predictor of serum PFOS and PFOA concentrations. In particular intake of meat and meat products was positively associated while intake of vegetables was inversely associated (P for trend CONCLUSION: In this study associations between PFOS and PFOA with serum cholesterol appeared unrelated to dietary intake and were similar in magnitude as the associations between saturated fat intake and serum cholesterol.

The potential toxicity of background exposure to perfluoroalkyl substances (PFASs) is currently under active investigation. Such investigations typically rely on a single measure of PFAS concentration, yet the longer-term reliability of a single measure has not been well characterized, especially among reproductive-aged women. Our aim was to investigate the association between PFAS plasma concentrations of 100 women in two consecutive pregnancies and explore changes in plasma concentration related to reproductive factors. The women in our study were enrolled in the Norwegian Mother and Child Cohort Study (MoBa) from 2003 to 2009. About half of them breastfed exclusively for 6 months and the rest of the participants did not breastfeed between the two consecutive pregnancies (median time between pregnancies: 18 months). Maternal blood was collected at mid-pregnancy and plasma was analyzed for 10 PFASs. Statistical analyses were restricted to 6 PFASs that were quantifiable in more than 80% of the samples. We estimated the correlation between repeated PFAS measurements, the percentage change between pregnancies and the effect of several reproductive factors in multivariate linear regression models of PFAS concentrations in the second pregnancy. The Pearson correlation coefficient between repeated PFAS measurements was, for perfluorooctane sulfonate (PFOS), 0.80; perfluorooctanoate (PFOA), 0.50; perfluorohexane sulfonate (PFHxS), 0.74; perfluorononanoate (PFNA), 0.39; perfluoroundecanoate (PFUnDA), 0.71; and perfluorodecanoate (PFDA), 0.60. Adjustment for maternal age, delivery year, and time and breastfeeding between pregnancies did not substantially affect the observed correlations. We found 44–47% median reductions in the concentrations of PFOS, PFOA and PFHxS between pregnancies, while the change in concentrations between pregnancies was smaller and more variable for PFNA, PFUnDA and PFDA. The variation in plasma concentrations in the second pregnancy was mainly accounted for by the concentration in the first pregnancy; for PFOS, PFOA, and PFNA, breastfeeding also accounted for a substantial proportion. In conclusion, we found the reliability of PFAS measurements in maternal plasma to be moderate to high, and in these data, several factors, especially breastfeeding, were related to plasma concentrations.

Perfluoroalkyl substances (PFASs) are chemicals with potential neurotoxic effects although the current evidence is still limited. This study investigated the association between perinatal exposure to perfluorooctanesulfonic acid (PFOS) and perfluorooctanoic acid (PFOA) and neuropsychological development assessed at 6, 12 and 24 months. We measured PFOS and PFOA in breast milk samples collected one month after delivery by mothers of children participating in the HUMIS study (Norway). Cognitive and psychomotor development was measured at 6 and at 24 months using the Ages and Stages Questionnaire (ASQ-II). Behavioral development was assessed using the infant–toddler symptom checklist (ITSC) at 12 and at 24 months. Weighted logistic regression and weighted negative binomial regression models were applied to analyze the associations between PFASs and ASQ-II and ITSC, respectively. The median concentration of PFOS was 110 ng/L, while the median for PFOA was 40 ng/L. We did not detect an increased risk of having an abnormal score in ASQ-II at 6 months or 24 months. Moreover, no consistent increase in behavioral problems assessed at 12 and 24 months by ITSC questionnaire was detected. We observed no association between perinatal PFOS and PFOA exposure and early neuropsychological development. Further longitudinal studies are needed to confirm the effects of these compounds on neuropsychological development in older children. Keywords: Nervous system, Child development, Neuropsychology, Perfluorooctanoic acid, Perfluorooctane sulfonic acid, Epidemiology

Background and aim: Phthalates have been implicated in respiratory disease, but this has hardly been addressed in infants. This study aims to investigate if the urinary concentration of phthalate m...

Perfluoroalkyl substances (PFAS) are persistent and ubiquitous environmental contaminants, and human exposure to these substances may be related to preeclampsia, a common pregnancy complication. Previous studies have found serum concentrations of PFAS to be positively associated with pregnancy-induced hypertension and preeclampsia in a population with high levels of exposure to perfluorooctanoate. Whether this association exists among pregnant women with background levels of PFAS exposure is unknown. Using data from the Norwegian Mother and Child Cohort Study conducted by the Norwegian Institute of Public Health, we carried out a study of nulliparous pregnant women enrolled in 2003-2007 (466 cases, 510 noncases) to estimate associations between PFAS concentrations and an independently validated diagnosis of preeclampsia. We measured levels of 9 PFAS in maternal plasma extracted midpregnancy; statistical analyses were restricted to 7 PFAS that were quantifiable in more than 50% of samples. In proportional hazards models adjusted for maternal age, prepregnancy body mass index (weight (kg)/height (m)(2)), educational level, and smoking status, we observed no strongly positive associations between PFAS levels and preeclampsia. We found an inverse association between preeclampsia and the highest quartile of perfluoroundecanoic acid concentration relative to the lowest quartile (hazard ratio = 0.55, 95% confidence interval: 0.38, 0.81). Overall, our findings do not support an increased risk of preeclampsia among nulliparous Norwegian women with background levels of PFAS exposure.

We examined whether perfluorooctanoate (PFOA) or perfluorooctane sulfonate (PFOS) had obesogenic effects and if they increased spontaneous intestinal tumorigenesis in the mouse model C57BL/6J-Min/+ (multiple intestinal neoplasia) after in utero exposure. The dams were exposed to PFOA or PFOS (0.01, 0.1 or 3.0mg/kg bw/day) by po gavage on GD1-17. The Min/+ and wild-type offspring were terminated at week 11 for examination of intestinal tumorigenesis or at week 20 for obesogenic effect, respectively. Body weights of the dams and pups were recorded throughout life. Food intake was determined at week 6 and 10. Blood glucose (non-fasted) was measured at week 6 and 11. No obesogenic effect of PFOA or PFOS was observed up to 20 weeks of age. PFOA or PFOS did not increase the incidence or number of tumors in the small intestine or colon of the Min/+ mice or affect their location along the intestines. Feed intake was not affected. There were some indications of toxicity of PFOA, but not of PFOS. There was lower survival of pups after 3.0mg/kg PFOA, lower body weight in pups after 3.0 and possibly 0.1mg/kg PFOA, and increased relative liver weight after 0.01 and possibly 0.1mg/kg PFOA. Plasma glucose was lower after 0.01 and 0.1mg/kg PFOA. In conclusion, exposure to PFOA and PFOS in utero with the doses used did not have obesogenic effect on either Min/+ or wild-type mice, at least not up to 11 or 20 weeks of age, nor increased intestinal tumorigenesis in Min/+ mice.

To examine alcohol and drug use among truck drivers compared to car or van drivers in Norway by analyzing samples of oral fluid.Drivers were selected for a voluntary and anonymous study using a stratified multistage cluster sampling procedure. Drivers of trucks were recruited at two control stations for heavy vehicles in southeastern Norway in collaboration with the Norwegian Roads Administration, and drivers of cars and vans were recruited in a roadside survey in collaboration with the mobile police service. Samples of oral fluid were taken by using the Statsure Saliva Sampler (Statsure Diagnostic Systems, Framingham, MA), and the drivers' gender, age, and nationality were recorded. Samples of oral fluid were analyzed for alcohol or drugs, in total 28 psychoactive substances.About 97 percent of the truck drivers and 94 percent of the car or van drivers agreed to participate in the study. Of the 882 studied truck drivers studied, 1.4 percent were female and 29.1 percent were Norwegian; of the 5305 car or van drivers, 27.6 percent were female and 90.9 percent were Norwegian. Alcohol or drugs were found in 1.9 and 6.6 percent of the samples from truck drivers and car/van drivers, respectively. The adjusted odds ratio (OR) for the detection of a psychoactive substance in a sample from a truck driver compared to car or van driver was 0.29; the 95 percent confidence interval (95% CI) was 0.17 to 0.53. The adjusted OR for the detection of an illegal drug was 0.42 (95% CI: 0.18-0.82), the adjusted OR for the detection of a psychoactive medicinal drug was 0.29 (95% CI: 0.13-0.68), and the adjusted OR for the detection of alcohol was 0.13 (95% CI: 0.02-1.10).The proportion of oral fluid samples containing psychoactive substances was lower for truck drivers than for car or van drivers.

Perfluorinated compounds (PFCs) comprise a large group of man-made fluorinated chemicals used in a number of consumer products and industrial applications. PFCs have shown to be persistent, bio-accumulative and widespread in the environment. Animal studies have demonstrated hepatotoxicity, immunotoxicity, developmental toxicity as well as hormonal effects. We investigated prenatal exposure to several PFCs and detected up to seven different PFCs in 123 paired samples of human maternal and cord blood, from a subcohort of the Norwegian Mother and Child Cohort Study (MoBa). The maternal and foetal levels were significantly correlated for all PFCs tested with median PFC concentrations in cord blood ranging between 30 and 79% of the maternal concentrations, demonstrating placental passage. The composition of the different PFCs varied between cord and maternal blood, with a higher proportion of shorter chained PFCs together with a higher amount of the branched isomers of perfluorooctane sulfonate (PFOS) in cord blood. Additionally, the sulfonate group seems to impede transfer efficiency. This indicates a selective placental passage of the different PFCs and hence a specific foetal exposure.

Objective To examine associations between environmental exposure to perfluoroalkyl substances (PFASs) and ovarian hormone concentrations in naturally cycling women. Design E2 and P were measured in saliva samples collected daily for a single menstrual cycle and concentrations of PFASs (including perfluoroctane sulfonate [PFOS] and perfluoroctanoic acid) were measured in serum samples collected during the same cycle. Setting Not applicable. Patient(s) A total of 178 healthy, naturally cycling women, aged 25–35 years. Intervention(s) None. Main Outcome Measure(s) Mean follicular E 2 (cycle days −7 to −1, where 0 is the day of ovulation); mean luteal P (cycle days +2 to 10). Result(s) Among nulliparous, but not parous women, PFOS concentrations were inversely associated with E 2 (β = −0.025, 95% CI −0.043, −0.007) and P (β = −0.027, 95% CI −0.048, −0.007). Similar, but weaker results were observed for perfluorooctanesulfonic acid. No associations were observed between other PFASs (including perfluoroctanoic acid) and ovarian steroid concentrations, nor were any associations noted in parous women. Conclusion(s) Our results demonstrate that PFOS and perfluorooctanesulfonic acid may be associated with decreased production of E 2 and P in reproductive age women. These results suggest a possible mechanism by which PFASs affect women's health, and underscore the importance of parity in research on PFASs and women's reproductive health.