Pesticide exposure, birth size, and gestational age in the ISA birth cohort, Costa Rica.

Purpose: To examine associations of prenatal biomarkers of pesticide exposure with birth size measures and length of gestation among newborns from the Infants' Environmental Health (ISA) birth cohort, Costa Rica. Methods: We included 386 singleton liveborn newborns with data on birth size measures, length of gestation, and maternal urinary biomarkers of chlorpyrifos, synthetic pyrethroids, mancozeb, pyrimethanil, and 2, 4-D during pregnancy. We associated biomarkers of exposure with birth outcomes using multivariate linear regression and generalized additive models. Results: Concentrations were highest for ethylene thiourea (ETU, metabolite of mancozeb), median = 3.40; p10-90 = 1.90-6.79 µg/L, followed by 3,5,6-trichloro-2-pyridinol (TCP, metabolite of chlorpyrifos) p50 = 1.76 p10-90 = 0.97-4.36 µg/L, and lowest for 2,4-D (p50 = 0.33 p10-90 = 0.18-1.07 µg/L). Among term newborns (≥37 weeks), higher prenatal TCP was associated with lower birth weight and smaller head circumference (e.g., ß per 10-fold-increase) during the second half of pregnancy = -129.6 (95% confidence interval [CI] = -255.8, -3.5) grams, and -0.61 (95% CI = -1.05, -0.17) centimeters, respectively. Also, among term newborns, prenatal 2,4-D was associated with lower birth weight (ß per 10-fold-increase = -125.1; 95% CI = -228.8, -21.5), smaller head circumference (ß = -0.41; 95% CI = -0.78, -0.03), and, during the second half of pregnancy, with shorter body length (ß = -0.58; 95% CI = -1.09, -0.07). Furthermore, ETU was nonlinearly associated with head circumference during the second half of pregnancy. Biomarkers of pyrethroids and pyrimethanil were not associated with birth size, and none of the biomarkers explained the length of gestation. Conclusions: Prenatal exposure to chlorpyrifos and 2,4-D, and, possibly, mancozeb/ETU, may impair fetal growth.

Socio-demographic inequalities influence differences in the chemical exposome among Swedish adolescents.

Relatively little is known about the relationship between socio-demographic factors and the chemical exposome in adolescent populations. This knowledge gap hampers global efforts to meet certain UN sustainability goals. The present work addresses this problem in Swedish adolescents by discerning patterns within the chemical exposome and identify demographic groups susceptible to heightened exposures. Enlisting the Riksmaten Adolescents 2016-17 (RMA) study population (N = 1082) in human-biomonitoring, and using proportional odds ordinal logistic regression models, we examined the associations between concentrations of a diverse array of substances (N = 63) with the determinants: gender, age, participant/maternal birth country income per capita level, parental education levels, and geographic place of living (longitude/latitude). Participant/maternal birth country exhibited a significant association with the concentrations of 46 substances, followed by gender (N = 41), and longitude (N = 37). Notably, individuals born in high-income countries by high-income country mothers demonstrated substantially higher estimated adjusted means (EAM) concentrations of polychlorinated biphenyls (PCBs), brominated flame retardants (BFRs) and per- and polyfluoroalkyl substances (PFASs) compared to those born in low-income countries by low-income country mothers. A reverse trend was observed for cobalt (Co), cadmium (Cd), lead (Pb), aluminium (Al), chlorinated pesticides, and phthalate metabolites. Males exhibited higher EAM concentrations of chromium (Cr), mercury (Hg), Pb, PCBs, chlorinated pesticides, BFRs and PFASs than females. In contrast, females displayed higher EAM concentrations of Mn, Co, Cd and metabolites of phthalates and phosphorous flame retardants, and phenolic substances. Geographical disparities, indicative of north-to-south or west-to-east substance concentrations gradients, were identified in Sweden. Only a limited number of lifestyle, physiological and dietary factors were identified as possible drivers of demographic inequalities for specific substances. This research underscores birth country, gender, and geographical disparities as contributors to exposure differences among Swedish adolescents. Identifying underlying drivers is crucial to addressing societal inequalities associated with chemical exposure and aligning with UN sustainability goals.

Exposure to Paracetamol in Early Pregnancy and the Risk of Developing Cerebral Palsy: A Case-Control Study Using Serum Samples.

OBJECTIVE: To investigate whether maternal paracetamol use in early pregnancy is associated with cerebral palsy (CP) in offspring. STUDY DESIGN: We conducted a registry and biobank-based case-control study with mother-child pairs. We identified CP cases (n = 322) born between 1995 and 2014 from a nationwide CP-registry. Randomly selected controls (n = 343) and extra preterm controls (n = 258) were obtained from a birth registry. For each mother, a single serum sample from early pregnancy (gestation weeks 10-14) was retrieved from a biobank and analyzed for serum concentrations of paracetamol, categorized into unexposed (<1 ng/ml), mildly exposed (1-100 ng/ml), and highly exposed (>100 ng/ml), and in quartiles. Analyses were performed using logistic regression and adjusted for potential confounders. Separate analyses were conducted including only those children born preterm and only those born term. RESULTS: Of the 923 participants, 36.8% were unexposed, 53.2% mildly exposed, and 10% highly exposed to paracetamol. Overall, prenatal exposure to paracetamol was not associated with CP. Sensitivity and subgroup analyses showed no clear associations between paracetamol and CP across strata of term/preterm birth as well as subtypes of CP. CONCLUSIONS: The present study does not support an association between intrauterine exposure to paracetamol in early pregnancy and the risk of CP. However, it is important to stress that the exposure estimate is based on a single serum sample.

Association of pesticide exposure with neurobehavioral outcomes among avocado farmworkers in Mexico.

BACKGROUND AND AIM: To date, few studies have focused on the health effects of pesticide exposure among avocado farmworkers. We examined the association of exposure to insecticides, fungicides, and herbicides with cognitive and mental health outcomes among these avocado workers from Michoacan, Mexico. MATERIALS AND METHODS: We conducted a cross-sectional study of 105 avocado farmworkers between May and August 2021. We collected data on self-reported pesticide use during the 12 months prior to the baseline survey and estimated annual exposure-intensity scores (EIS) using a semi-quantitative exposure algorithm. We calculated specific gravity adjusted average concentrations of 12 insecticide, fungicide, or herbicide metabolites measured in urine samples collected during two study visits (8-10 weeks apart). We assessed participants' cognitive function and psychological distress using the NIH Toolbox Cognition Battery and the Brief Symptom Inventory 18 (BSI-18), respectively. We examined individual associations of EIS and urinary pesticide metabolites with neurobehavioral outcomes using generalized linear regression models. We also implemented Bayesian Weighted Quantile Sum (BWQS) regression to evaluate the association between a pesticide metabolite mixture and neurobehavioral outcomes. RESULTS: In individual models, after adjusting for multiple comparisons, higher concentrations of hydroxy-tebuconazole (OH-TEB, metabolite of fungicide tebuconazole) were associated with higher anxiety (IRR per two-fold increase in concentrations = 1.26, 95% CI:1.08, 1.48) and Global Severity Index (GSI) (IRR = 1.89, 95% CI:1.36, 2.75) scores, whereas higher concentrations of 3,5,6-trichloro-2-pyridinol (TCPy, metabolite of chlorpyrifos) were associated with lower GSI scores (IRR = 0.69, 95% CI: 0.56, 0.85). In BWQS analyses, we found evidence of a mixture association of urinary pesticide metabolites with higher anxiety (IRR = 1.72, 95% CrI: 1.12, 2.55), depression (IRR = 4.60, 95% CrI: 2.19, 9.43), and GSI (IRR = 1.99, 95% CrI: 1.39, 2.79) scores. OH-TEB and hydroxy-thiabendazole (metabolite of fungicide thiabendazole) combined contributed 54%, 40%, and 54% to the mixture effect in the anxiety symptoms, depression symptoms, and overall psychological distress models, respectively. CONCLUSIONS: We found that exposure to tebuconazole and thiabendazole, fungicides whose effects have been rarely studied in humans, may be associated with increased psychological distress among avocado farmworkers. We also observed that exposure to chlorpyrifos may be associated with decreased psychological distress.

EDC mixtures during pregnancy and body fat at 7 years of age in a Swedish cohort, the SELMA study.

BACKGROUND: Some endocrine disrupting chemicals (EDC), are "obesogens" and have been associated with overweight and obesity in children. Daily exposure to different classes of EDCs demands for research with mixtures approach. OBJECTIVES: This study evaluates the association, considering sex-specific effects, between prenatal exposure to EDC mixture and children's body fat at seven years of age. METHODS: A total of 26 EDCs were assessed in prenatal urine and serum samples from first trimester in pregnancy from 737 mother-child pairs participating in the Swedish Environmental Longitudinal, Mother and child, Asthma and allergy (SELMA) study. An indicator for children's "overall body fat" was calculated, using principal component analysis (PCA), based on BMI, percent body fat, waist, and skinfolds measured at seven years of age. Weighted quantile sum (WQS) regression was used to assess associations between EDC mixture and children's body fat. RESULTS: Principal component (PC1) represented 83.6 % of the variance, suitable as indicator for children's "overall body fat", with positive loadings of 0.40-0.42 for each body fat measure. A significant interaction term, WQS*sex, confirmed associations in the opposite direction for boys and girls. Higher prenatal exposure to EDC mixture was borderline significant with more "overall body fat" for boys (Mean ß = 0.20; 95 % CI: -0.13, 0.53) and less for girls (Mean ß = -0.23; 95 % CI: -0.58, 0.13). Also, higher prenatal exposure to EDC mixture was borderline significant with more percent body fat (standardized score) for boys (Mean ß = 0.09; 95 % CI: -0.04, 0.21) and less for girls (Mean ß = -0.10 (-0.26, 0.05). The chemicals of concern included bisphenols, phthalates, PFAS, PAH, and pesticides with different patterns for boys and girls. DISCUSSION: Borderline significant associations were found between prenatal exposure to a mixture of EDCs and children's body fat. The associations in opposite directions suggests that prenatal exposure to EDCs may present sex-specific effects on children's body fat.

Prenatal current-use pesticide exposure and children's neurodevelopment at one year of age in the Infants' Environmental Health (ISA) birth cohort, Costa Rica.

BACKGROUND: Pesticide exposure may affect young children's neurodevelopment, but only few cohort studies have addressed possible effects of non-organophosphate pesticides. OBJECTIVE: We evaluated associations between prenatal current-use pesticide exposure and neurodevelopmental outcomes among 1-year-old children from the Infants' Environmental Health (ISA) birth cohort. METHODS: To determine prenatal pesticide exposure, we measured biomarkers of pyrimethanil, chlorpyrifos, synthetic pyrethroids, and 2,4-D in urine samples among 355 women, 1-3 times during pregnancy. One-year post-partum, we evaluated children's neurodevelopment with the Bayley Scales of Infant and Toddler Development 3rd edition (BSID-III). We assessed associations between exposures and neurodevelopmental outcomes (composite and z-scores) using single-chemical linear regression models adjusted for possible confounders (maternal education, parity, sex, gestational age at birth, child age, HOME-score, location of assessment, biomarkers of mancozeb), and studied effect-modification by sex. We evaluated non-linear associations of multiple pesticide exposures with Bayesian kernel machine regression (BKMR). RESULTS: We found higher prenatal urinary 2,4-D concentrations were associated with lower language (ßper ten-fold increase = -2.0, 95 % confidence interval (CI) = -3.5, -0.5) and motor (ßper ten-fold increase = -2.2, 95 %CI = -4.2, -0.1) composite scores among all children. Also, higher chlorpyrifos exposure [measured as urinary 3,5,6-trichloro-2-pyridinol (TCPy)] was associated with lower cognitive composite scores (ßper ten-fold increase = -1.9, 95 %CI = -4.7, 0.8), and lower motor composite scores among boys (ßper ten-fold increase = -3.8, 95 % CI = -7.7, 0.1) but not girls (ßper ten-fold increase = 2.3, 95 %CI = -1.6, 6.3, pINT = 0.11). Finally, higher pyrimethanil was associated with lower language abilities among girls, but not boys. Pyrethroid metabolite concentrations did not explain variability in BSID-III composite scores. Associations were similar for BSID-III z-scores, and we found no evidence for non-linear associations or mixture effects. DISCUSSION: Prenatal exposure to common-use pesticides may affect children's neurodevelopment at 1-year of age, some effects may be sex-specific.

OMICs Signatures Linking Persistent Organic Pollutants to Cardiovascular Disease in the Swedish Mammography Cohort.

Cardiovascular disease (CVD) development may be linked to persistent organic pollutants (POPs), including organochlorine compounds (OCs) and perfluoroalkyl and polyfluoroalkyl substances (PFAS). To explore underlying mechanisms, we investigated metabolites, proteins, and genes linking POPs with CVD risk. We used data from a nested case-control study on myocardial infarction (MI) and stroke from the Swedish Mammography Cohort - Clinical (n = 657 subjects). OCs, PFAS, and multiomics (9511 liquid chromatography-mass spectrometry (LC-MS) metabolite features; 248 proteins; 8110 gene variants) were measured in baseline plasma. POP-related omics features were selected using random forest followed by Spearman correlation adjusted for confounders. From these, CVD-related omics features were selected using conditional logistic regression. Finally, 29 (for OCs) and 12 (for PFAS) unique features associated with POPs and CVD. One omics subpattern, driven by lipids and inflammatory proteins, associated with MI (OR = 2.03; 95% CI = 1.47; 2.79), OCs, age, and BMI, and correlated negatively with PFAS. Another subpattern, driven by carnitines, associated with stroke (OR = 1.55; 95% CI = 1.16; 2.09), OCs, and age, but not with PFAS. This may imply that OCs and PFAS associate with different omics patterns with opposite effects on CVD risk, but more research is needed to disentangle potential modifications by other factors.

Inflammation-related proteins in blood after dermal exposure to some common chemicals depend on the skin barrier gene filaggrin - a human experimental study.

Filaggrin (FLG), a skin barrier protein, is associated with higher dermal uptake of some chemicals in carriers of loss-of-function (null) mutations. This study investigates FLG mutations and systemic effects following dermal exposure to chemicals. Individuals (n = 23 FLG null, n = 31 FLG wt) were simultaneously exposed to pyrimethanil, pyrene, oxybenzone, and nickel ions for 4 h. Pre- and post-exposure, 25-hydroxyvitamin D3 (25(OH)D3, LC-MS/MS) and 92 inflammation-related proteins (proximity-extension assay) were measured. FLG null carriers exhibited significantly higher 25(OH)D3 concentrations than wt carriers, both pre- and post-exposure. Eleven proteins differed in abundance post- vs pre-exposure among FLG null carriers, and 22 proteins among wt carriers (three proteins overlapped). Twelve proteins showed median differences (post- vs pre-exposure) between FLG null and wt carriers. Overall, FLG null carriers showed an increase, while FLG wt carriers showed a decrease in inflammation-related proteins. These findings suggest FLG-dependent differences in susceptibility to systemic effects following simultaneous dermal chemical exposure.

High-resolution mass spectrometry identifies delayed biomarkers for improved precision in acetaminophen/paracetamol human biomonitoring.

Paracetamol/acetaminophen (N-acetyl-p-aminophenol, APAP) is a top selling analgesic used in more than 600 prescription and non-prescription pharmaceuticals. To study efficiently some of the potential undesirable effects associated with increasing APAP consumption (e.g., developmental disorders, drug-induced liver injury), there is a need to improve current APAP biomonitoring methods that are limited by APAP short half-life. Here, we demonstrate using high-resolution mass spectrometry (HRMS) in several human studies that APAP thiomethyl metabolite conjugates (S-methyl-3-thioacetaminophen sulfate and S-methyl-3-thioacetaminophen sulphoxide sulfate) are stable biomarkers with delayed excretion rates compared to conventional APAP metabolites, that could provide a more reliable history of APAP ingestion in epidemiological studies. We also show that these biomarkers could serve as relevant clinical markers to diagnose APAP acute intoxication in overdosed patients, when free APAP have nearly disappeared from blood. Using in vitro liver models (HepaRG cells and primary human hepatocytes), we then confirm that these thiomethyl metabolites are directly linked to the toxic N-acetyl-p-benzoquinone imine (NAPQI) elimination, and produced via an overlooked pathway called the thiomethyl shunt pathway. Further studies will be needed to determine whether the production of the reactive hepatotoxic NAPQI metabolites is currently underestimated in human. Nevertheless, these biomarkers could already serve to improve APAP human biomonitoring, and investigate, for instance, inter-individual variability in NAPQI production to study underlying causes involved in APAP-induced hepatotoxicity. Overall, our findings demonstrate the potential of exposomics-based HRMS approach to advance towards a better precision for human biomonitoring.

Paternal pre-conceptional smoking and semen quality in the adult son.

BACKGROUND: Growing evidence suggests intergenerational effects of paternal pre-conceptional smoking through the germ line, but its specific impact on offspring semen quality remains uncertain because of challenges in isolating paternal exposure from maternal passive smoking or underreporting. METHODS: We reran previous analyses estimating differences in semen parameters and testicular size according to paternal smoking in 867 young adult men, adding first-trimester maternal plasma cotinine to the original adjustment for maternal self-reported smoking. We also estimated differences in sperm DNA fragmentation. Paternal smoking was reported by the pregnant women around gestational week 16. Analyses were additionally adjusted for household occupational status, parental ages at birth, maternal pre-pregnancy body mass index and alcohol consumption, and abstinence time, and accounted for spillage, minutes from ejaculation to analysis, and son's own smoking. RESULTS: We found no association between paternal preconceptional smoking and any of the semen parameters or testicular size. Adjustment for son's own smoking did not change results. DISCUSSION: While maternal plasma cotinine offers an objective measure of tobacco exposure and allows for a more thorough adjustment of maternal smoking, the high correlation between paternal pre-conceptional smoking and maternal cotinine exposure may, have resulted in overadjustment removing some paternal effect. Inability to distinguish between paternal never smokers and former smokers, may have led to misclassification of paternal pre-conceptional smoking and underestimation of associations. CONCLUSION: We found no support for an independent association between paternal pre-conceptional smoking and semen quality in young adult sons, but studies with more detailed paternal smoking history are needed before firm conclusions can be drawn.

Evaporation of serum after long-term biobank storage: A chemical analysis of maternal serum from a large Danish pregnancy screening registry.

BACKGROUND: Relying on freezer stored biospecimens is preferred in epidemiolocal studies exploring environmental pregnancy exposures and later offspring health. Storage duration may increase the pre-analytical variability, potentially adding measurement uncertainty. We investigated evaporation of maternal serum after long-term biobank storage using ions (sodium, Na+; chloride, Cl-) recognized for stability and relatively narrow normal biological reference ranges in human serum. METHODS: A chemical analysis study of 275 biobanked second trimester maternal serum from a large Danish pregnancy screening registry. Serum samples were collected between 1985-1995 and stored at -20°C. Ion concentrations were quantified with indirect potentiometry using a Roche Cobas 6000 analyzer and compared according to storage time and normal biological ranges in second trimester. Ion concentrations were also compared with normal biological variation assessed by baseline Na+ and Cl- serum concentrations from a separate cohort of 24,199 non-pregnant women measured before freezing with the same instrument. RESULTS: The overall mean ion concentrations in biobanked serum were 147.5 mmol/L for Na+ and 109.7 for Cl-. No marked linear storage effects were observed according to storage time. Ion concentrations were consistently high across sampling years, especially for specific sampling years, and a relatively large proportion were outside respective normal ranges in second trimester: 38.9% for Na+ and 43.6% for Cl-. Some variation in concentrations was also evident in baseline serum used as quality controls. CONCLUSIONS: Elevated ion concentrations suggest evaporation, but independent of storage duration in the present study (27-37 years). Any evaporation may have occurred prior to freezer storage or during the first 27 years. Other pre-analytical factors such as low serum volume have likely influenced the concentrations, particularly given the high within year variability. Overall, we consider the biobanked serum samples internally comparable to enable their use in epidemiological studies.

Maternal Serum Concentrations of Per- and Polyfluoroalkyl Substances in Early Pregnancy and Small for Gestational Age in Southern Sweden.

Small for gestational age (SGA) is considered an adverse birth outcome. Per- and polyfluoralkyl substances (PFAS) have become increasingly investigated as contributing environmental factors, thus far with inconclusive results. The current study aimed to investigate the hypothesized association between increased maternal PFAS levels in early pregnancy and an increased risk for SGA birth. This population-based study used data from a sample of children born in Scania, Southern Sweden, between 1995 and 2009. Two groups were compared: cases born with SGA (n = 298) and non-SGA controls (n = 580). The cases consisted of two subgroups: one included women whose children's growth in late pregnancy was in the lowest quartile, and another included women from the remaining growth quartiles. Corresponding maternal serum samples were collected from a biobank and analyzed for concentrations of four types of PFAS: perfluorooctanoic acid (PFOA), perfluorononanoic acid (PFNA), perfluorohexane sulfonic acid (PFHxS), and perfluorooctane sulfonic acid (PFOS) using liquid chromatography-tandem mass spectrometry (LC/MS/MS). The results were combined with information from birth registers and analyzed using Mann-Whitney U-tests and logistic regression-unadjusted as well as adjusted for potential confounders. In conclusion, elevated maternal concentrations of PFAS were not associated with an increased risk of SGA birth. However, significant ORs were observed in a subgroup analysis restricted to women of Nordic origin (unadjusted OR 3.2 and adjusted OR 2.4) for PFHxS.

Prenatal exposures to mixtures of endocrine disrupting chemicals and sex-specific associations with children's BMI and overweight at 5.5 years of age in the SELMA study.

BACKGROUND: Prenatal exposure to mixtures of endocrine disrupting chemicals (EDC) has the potential to disrupt human metabolism. Prenatal periods are especially sensitive as many developmental processes are regulated by hormones. Prenatal exposure to EDCs has inconsistently been associated with children's body mass index (BMI) and obesity. The objective of this study was to investigate if prenatal exposure to a mixture of EDCs was associated with children's BMI and overweight (ISO-BMI ≥ 25) at 5.5 years of age, and if there were sex-specific effects. METHODS: A total of 1,105 mother-child pairs with complete data on prenatal EDCs concentrations (e.g., phthalates, non-phthalate plasticizers, phenols, PAH, pesticides, PFAS, organochlorine pesticides, and PCBs), children's measured height and weight, and selected covariates in the Swedish Environmental Longitudinal, Mother and child, Asthma and allergy (SELMA) study were included in this analysis. The mixture effect of EDCs with children's BMI and overweight was assessed using WQS regression with 100 repeated holdouts. A positively associated WQS index with higher BMI and odds of overweight was derived. Models with interaction term and stratified weights by sex was applied in order to evaluate sex-specific associations. RESULTS: A significant WQS*sex interaction term was identified and associations for boys and girls were in opposite directions. Higher prenatal exposure to a mixture of EDCs was associated with lower BMI (Mean ß = -0.19, 95%CI: -0.40, 0.01) and lower odds of overweight (Mean OR = 0.72, 95%CI: 0.48, 1.04) among girls with borderline significance. However, the association among boys did not reach statistical significance. Among girls, the possible chemicals of concern were MEP, 2-OHPH, BPF, BPS, DPP and PFNA. CONCLUSION: Prenatal exposure to a mixture of EDCs was associated with lower BMI and overweight among girls, and non-significant associations among boys. Chemicals of concern for girls included phthalates, non-phthalate plasticizers, bisphenols, PAHs, and PFAS.

High Exposure to Perfluoroalkyl Substances and Antibody Responses to SARS-CoV-2 mRNA Vaccine-an Observational Study in Adults from Ronneby, Sweden.

BACKGROUND: Per- and polyfluoroalkyl substances (PFAS) are widely used, environmentally ubiquitous, and stable chemicals that have been associated with lower vaccine-induced antibody responses in children; however, data on adults are limited. The drinking water from one of the two waterworks in Ronneby, Sweden, was heavily contaminated for decades with PFAS from firefighting foams, primarily perfluorohexane sulfonic acid and perfluorooctanesulfonic acid (PFOS). Vaccination against SARS-CoV-2 offered a unique opportunity to investigate antibody responses to primary vaccination in adults who had been exposed to PFAS. OBJECTIVES: Our objective was to evaluate associations between PFAS, across a wide range of exposure levels, and antibody responses in adults 5 wk and 6 months after a two-dose vaccination regime against SARS-CoV-2. METHODS: Adults age 20-60 y from Ronneby (n=309, median PFOS serum level 47 ng/mL, fifth to 95th percentile 4-213 ng/mL) and a group with background exposure (n=47, median PFOS serum level 4 ng/mL) received two doses of the Spikevax (Moderna) mRNA vaccine. The levels of seven PFAS were measured in serum before vaccination. Serum immunoglobulin G antibodies against the SARS-CoV-2 spike antigen (S-Abs) were measured before vaccination and at 5 wk (n=350) and 6 months (n=329) after the second vaccine dose. Linear regression analyses were fitted against current, historical, and prenatal exposure to PFAS, adjusting for sex, age, and smoking, excluding individuals with previous SARS-CoV-2-infection. RESULTS: PFAS exposure, regardless of how it was estimated, was not negatively associated with antibody levels 5 wk [current PFOS: -0.5% S-Abs/PFOS interquartile range (IQR); 95% confidence interval (CI): -8, 7] or 6 months (current PFOS: 3% S-Abs/PFOS IQR; 95% CI: -6, 12) after COVID-19 vaccination. DISCUSSION: Following a strict study protocol, rigorous study design, and few dropouts, we found no indication that PFAS exposure negatively affected antibody responses to COVID-19 mRNA vaccination for up to 6 months after vaccination. https://doi.org/10.1289/EHP11847.

Association of endocrine disrupting chemicals exposure with human chorionic gonadotropin concentrations in pregnancy.

BACKGROUND: Human chorionic gonadotropin (hCG) is produced by the placenta and plays an essential role in the maintenance of pregnancy. Endocrine disrupting chemicals (EDCs) have the potential to interfere with functions related to the production and secretion of hCG; however associations between exposure to EDCs and hCG concentrations in humans remain to be elucidated. OBJECTIVES: To investigate the association of urinary, serum and plasma concentrations of EDCs during pregnancy with serum hCG concentrations. METHODS: We utilized data form the Swedish Environmental Longitudinal, Mother and child, Asthma and allergy (SELMA) study. We investigated the association of 26 EDCs measured in early pregnancy urine or blood with serum hCG concentrations using multi-variable adjusted linear regression models per EDC and Weighted Quantile Sum (WQS) regression with repeated holdout validation for the EDCs mixture. RESULTS: In 2,039 included women, higher exposure to bisphenol A was associated with lower hCG (beta [95% CI]: -0.06 [-0.11 to -0.002]) while higher triclosan exposure was associated with a higher hCG (0.02 [0.003 to 0.04]). Higher exposure to several phthalates, including mono-ethyl and mono-butyl phthalates (MEP and MBP) as well as metabolites of di-2-ethylhexyl phthalate (DEHP) was associated with a lower hCG (beta [95% CI] for sum of DEHP metabolites: -0.13 [-0.19 to -0.07]). Likewise, higher exposure to several polychlorinated biphenyls (PCBs) was associated with a lower hCG. In the WQS regression, each quartile increase in the EDCs mixture was associated with -0.27 lower hCG (95% CI: -0.34 to -0.19). DISCUSSION: Higher exposure to several EDCs during pregnancy was associated with a lower hCG; and despite the small effect sizes, still indicating that the exposure may negatively affect production or secretion of hCG by the placenta. Our results provide the impetus for future experimental studies to investigate the placenta as a target organ for adverse effects of EDCs.

Exposure to per- and polyfluoroalkyl substances in early pregnancy and risk of cerebral palsy in children.

BACKGROUND: Most cerebral palsy (CP) cases have an unexplained etiology, but a role for environmental exposures has been suggested. One purported environmental risk factor is exposure to endocrine-disrupting pollutants specifically per- and polyfluoroalkyl substances (PFAS). OBJECTIVES: We investigated the association between prenatal PFAS exposures and CP in Swedish children. METHODS: In this case-control study, 322 CP cases, 343 population controls, and 258 preterm controls were identified from a birth registry in combination with a CP follow-up program from 1995 to 2014 and linked to a biobank which contains serum samples from week 10-14 of pregnancy. Maternal serum concentrations of four PFAS compounds: perfluorohexane sulfonate (PFHxS), perfluorooctanoic acid (PFOA), perfluorononanoic acid (PFNA), and perfluorooctane sulfonate (PFOS) were analyzed using liquid chromatography-tandem-mass-spectrometry. We estimated odds ratios (ORs) and 95 % confidence intervals (CIs) for CP and each PFAS in quartiles and as continuous variables controlling for various sociodemographic and lifestyle factors. RESULTS: In crude and adjusted analyses, we did not find consistent evidence of associations between serum PFHxS, PFOA, PFNA, PFOS and concentrations in early pregnancy and CP, except in preterm infants. The ORs comparing the highest PFAS quartiles to the lowest were 1.05 (95 % CI: 0.63-1.76), 0.96 (95 % CI: 0.55-1.68), 0.71 (95 % CI: 0.41-1.25), and 1.17 (95 % CI: 0.61-2.26), for PFHxS, PFOA, PFNA, and PFOS, respectively. Some positive associations were observed for preterm infants, but the results were imprecise. Similar patterns were observed in analyses treating PFAS as continuous variables. CONCLUSIONS: In this study, we found little evidence that early pregnancy prenatal exposure to PFHxS, PFOA, PFNA, or PFOS increases the risk of CP. However, some positive associations were observed for preterm cases and warrant further investigation.

Assessing tobacco use in Swedish young adults from self-report and urinary cotinine: a validation study using the BAMSE birth cohort.

OBJECTIVES: Studies on health effects of tobacco often rely on self-reported exposure data, which is subjective and can lead to misclassification. The aim of this study was to describe the prevalence of cigarette smoking, snus and e-cigarette use, as well as to validate self-reported tobacco use among young adults in Sweden. METHOD: Participants of a population-based Swedish cohort (n=3052), aged 22-25 years, assessed their tobacco use in a web questionnaire. Urinary cotinine was analysed in a subsample of the study population (n=998). The agreement between self-reported tobacco use and urinary cotinine was assessed using Cohen's Kappa coefficient (κ) at a cut-off level of 50 ng/mL. RESULTS: Patterns of tobacco use differed between men and women. Among men, 20.0% reported daily snus use, 5.8% daily cigarette smoking and 5.6% any e-cigarette use. In contrast, 3.2% of the women reported daily snus use, 9.0% daily cigarette smoking and 2.4% any e-cigarette use. Among the tobacco use categories, daily snus users had the highest levels of cotinine. Of reported non-tobacco users, 3.5% had cotinine levels above the cut-off, compared with 68.0% among both occasional cigarette smokers and snus users, 67.5% among all e-cigarette users and 94.7% and 97.8% among daily cigarette smokers and snus users, respectively. Agreement between self-reported tobacco use and urinary cotinine was classified as strong for daily use of cigarettes (κ=0.824) and snus (κ=0.861), while moderate to weak for occasional smoking (κ=0.618), occasional snus use (κ=0.573) and any e-cigarette use (κ=0.576). CONCLUSIONS: We found high validity of self-reported tobacco use in our study population, particularly for daily tobacco use. Further, we found that daily snus users were exposed to high levels of cotinine. Together with previous findings, our results indicate good validity of self-reported tobacco use among young adults.

Detection of the fungicide transformation product 4-hydroxychlorothalonil in serum of pregnant women from Sweden and Costa Rica.

BACKGROUND: 4-hydroxychlorothalonil (HCT, R182281), a transformation product of the fungicide chlorothalonil, was recently identified in human serum and breast milk. There are indications that HCT may be more toxic and environmentally persistent than chlorothalonil. OBJECTIVE: Our aim was to investigate serum concentrations of HCT in pregnant women in Sweden and Costa Rica. METHODS: We developed a quantitative analytical method for HCT using liquid chromatography tandem mass spectrometry. We measured HCT in 1808 serum samples from pregnant women from the general population in Sweden (1997-2015) and in 632 samples from 393 pregnant women from an agricultural population in Costa Rica (2010-2011). In Swedish samples, we assessed time trends and investigated seasonality. In the Costa Rican samples, we evaluated variability between and within women and explanatory variables of HCT concentrations. RESULTS: HCT was detected in all serum samples, and the limit of detection was 0.1 µg/L. The median HCT concentration in the Swedish samples was 4.1 µg/L (interquartile range [IQR] of 2.9 - 5.8 µg/L), and 3.9 times higher in the Costa Rican samples (median: 16.1 µg/L; IQR: 10.6 - 25.0 µg/L). We found clear seasonal variation with higher concentrations in the first half of each year among Swedish women. In the Costa Rican study, women working in agriculture and living near banana plantations had higher HCT concentrations, whilst higher parity and having a partner working in agriculture were associated with decreased HCT, and no clear seasonal pattern was observed. IMPACT STATEMENT: For the first time, this study quantifies human exposure to the fungicide chlorothalonil and/or its transformation product 4-hydroxychlorothalonil (HCT, R182281) and finds higher serum concentrations in women from a tropical agricultural setting as compared with women from the general population in Sweden.

Exposure of Swedish adolescents to elements, persistent organic pollutants (POPs), and rapidly excreted substances - The Riksmaten adolescents 2016-17 national survey.

Adolescence is a period of significant physiological changes, and likely a sensitive window to chemical exposure. Few nation-wide population-based studies of chemical body burdens in adolescents have been published. In the national dietary survey Riksmaten Adolescents (RMA) 2016-17, over 13 chemical substance groups, including elements, chlorinated/brominated/fluorinated persistent organic pollutants (POPs) were analysed in blood, and in urine metabolites of phthalates/phthalate alternatives, phosphorous flame retardants, polycyclic aromatic hydrocarbons (PAHs), and pesticides, along with bisphenols and biocide/preservative/antioxidant/UV filter substances (N = 1082, ages 11-21). The aim was to characterize the body burdens in a representative population of adolescents in Sweden, and to compare results with human biomonitoring guidance values (HBM-GVs). Cluster analyses and Spearman's rank order correlations suggested that concentrations of substances with known common exposure sources and similar toxicokinetics formed obvious clusters and showed moderate to very strong correlations (r ≥ 0.4). No clusters were formed between substances from different matrices. Geometric mean (GM) concentrations of the substances were generally less than 3-fold different from those observed among adolescents in NHANES (USA 2015-16) and GerES V (Germany 2014-17). Notable exceptions were brominated diphenyl ethers (PBDEs) with >20-fold lower GM concentrations, and the biocide triclosan and ultraviolet (UV) filter benzophenone-3 with >15-fold lower mean concentrations in RMA compared to NHANES. Exceedance of the most conservative HBM-GVs were observed for aluminium (Al, 26% of subjects), perfluorooctanesulfonic acid (PFOS, 19%), perfluorooctanoic acid (PFOA, 12%), lead (Pb, 12%), MBP (dibutyl phthalate metabolite, 4.8%), hexachlorobenzene (HCB, 3.1%) and 3-phenoxybenzoic acid (PBA, pyrethroid metabolite, 2.2%). Males showed a higher proportion of exceedances than females for Pb, HCB and PFOS; otherwise no gender-related differences in exceedances were observed. A higher proportion of males than females had a Hazard Index (HI) of substances with liver and kidney toxicity and neurotoxicity >1. Industrialized countries with similarly high standards of living, with some exceptions, show comparable average body burdens of a variety of toxic chemicals among adolescents from the general population. The exceedances of HBM-GVs and HIs strongly suggests that further efforts to limit chemical exposure are warranted.