Pesticides used in agriculture are designed to protect crops against unwanted species, such as weeds, insects, and fungus. Many compounds target the nervous system of insect pests. Because of the ...similarity in brain biochemistry, such pesticides may also be neurotoxic to humans. Concerns have been raised that the developing brain may be particularly vulnerable to adverse effects of neurotoxic pesticides. Current requirements for safety testing do not include developmental neurotoxicity. We therefore undertook a systematic evaluation of published evidence on neurotoxicity of pesticides in current use, with specific emphasis on risks during early development. Epidemiologic studies show associations with neurodevelopmental deficits, but mainly deal with mixed exposures to pesticides. Laboratory experimental studies using model compounds suggest that many pesticides currently used in Europe--including organophosphates, carbamates, pyrethroids, ethylenebisdithiocarbamates, and chlorophenoxy herbicides--can cause neurodevelopmental toxicity. Adverse effects on brain development can be severe and irreversible. Prevention should therefore be a public health priority. The occurrence of residues in food and other types of human exposures should be prevented with regard to the pesticide groups that are known to be neurotoxic. For other substances, given their widespread use and the unique vulnerability of the developing brain, the general lack of data on developmental neurotoxicity calls for investment in targeted research. While awaiting more definite evidence, existing uncertainties should be considered in light of the need for precautionary action to protect brain development.
Perfluorinated compounds (PFCs) have been in use for more than 60 years. Perfluorooctanoic acid (PFOA) was a primary PFC product at the 3M facility in Cottage Grove, Minnesota, but perfluorooctane ...sulfonate (PFOS) and other PFCs were also produced. The PFCs show high thermal, chemical, and biological inertness-properties that make them useful for certain industrial purposes, but at the same time also resulted in environmental persistence and potential human health risk. Little was published in scientific journals on PFC toxicology until the 1980s, perhaps because compounds resistant to breakdown were erroneously considered inert. Gradually, evidence for persistent, bioaccumulative effects has emerged, raising warning signs. A chronology of important events in understanding PFC health risks is provided in the Figure.
•PFAS exposure associated with systolic and diastolic blood pressure in pregnancy.•No clear associations between PFAS exposure and PE or GH were found.•Blood pressure increase was small but at a ...population level this may increase hypertension.•This has potential long term health implications for both the mother and the child.
Previous studies of association between exposure to poly- and perfluoroalkyl substances (PFAS) and gestational hypertension (GH) and preeclampsia (PE) have shown conflicting results, but most dichotomized outcome and did not study continuous blood pressure (BP) changes.
To study the association between PFAS exposure in early pregnancy and maternal BP trajectories in pregnancy, gestational hypertension and preeclampsia.
1436 women were enrolled in the Odense Child Cohort in early pregnancy and had a serum sample drawn, from which perfluorohexane sulfonic acid (PFHxS), perfluorooctane sulfonic acid (PFOS), perfluorooctanoic acid (PFOA), perfluorononanoic acid (PFNA) and perfluorodecanoic acid (PFDA) were measured using LC–MS/MS. Repeated BP measurements through pregnancy and information on PE were obtained from hospital files. Adjusted linear mixed models were used to investigate association between PFAS exposure and BP trajectory. Associations between PFAS and PE and GH were assessed by Cox proportional hazards model.
All women had measurable concentrations of PFAS. In all of many comparisons higher PFAS exposure (apart from PFHxS) was associated with higher systolic (SBP) and diastolic (DBP) blood pressures, although not all were significant, which is unlikely to be due to chance. After adjustment, each doubling in PFOS or PFOA exposure was associated with 0.47 mmHg (95% CI: −0.13; 1.08) and 0.36 mmHg (−0.19; 0.92) higher SBP; and 0.58 mmHg (0.13; 1.04) and 0.37 mmHg (−0.05; 0.79) higher DBP. No clear associations between PFAS exposure and PE or GH were found.
The magnitude of the association between PFAS exposure and BP might appear small, statistically non-significant and the possible clinical importance low. However, at a population level this may slightly shift the distribution of BP towards an increased incidence of GH. If BP increases in pregnancy, it may have long-term impact on health not only of the pregnant woman but also of her offspring.
At the time that Paracelsus coined his famous dictum, ‘What is there that is not poison? All things are poison and nothing is without poison. Solely the dose determines that a thing is not a poison’, ...embryonic toxicology was a fairly focused discipline that mainly dealt with occupational poisonings and side effects of pharmaceuticals, such as mercury. While Paracelsus paved the way for the modern threshold concept and the no‐adverse effect level, modern‐day toxicology is now tussling with highly complex issues, such as developmental exposures, genetic predisposition and other sources of hypersusceptibility, multiple causes of underestimated toxicity, and the continuous presence of uncertainty, even in regard to otherwise well‐studied mercury compounds. Further, the wealth of industrial chemicals now challenges the ‘untested‐chemical assumption’, that the lack of documentation means that toxic potentials can be ignored. Unfortunately, in its ambition to provide solid evidence, toxicology has been pushed into almost endless replications, as evidenced by the thousands of toxicology publications every year that focus on toxic metals, including mercury, while less well‐known hazards are ignored. From a public health viewpoint, toxicology needs to provide better guidance on decision‐making under ever‐present uncertainty. In this role, we need to learn from the stalwart Paracelsus the insistence on relying on facts rather than authority alone to protect against chemical hazards.
Perfluorinated alkylated substances (PFAS) have been extensively used in consumer products and humans are widely exposed to these persistent compounds. A recent study found no association between ...exposure to perfluorooctanoic acid (PFOA) and perfluorooctanesulfonic acid (PFOS) and miscarriage, but no studies have examined adverse effect of the more recently introduced PFASs. We therefore conducted a case-control study within a population-based, prospective cohort during 2010-2012. Newly pregnant women residing in the Municipality of Odense, Denmark were invited to enroll in the Odense Child Cohort at their first antenatal visit before pregnancy week 12. Among a total of 2,874 participating women, 88 suffered a miscarriage and 59 had stored serum samples, of which 56 occurred before gestational week 12. They were compared to a random sample (N=336) of delivering women, who had also donated serum samples before week 12. Using a case-control design, 51 of the women suffering a miscarriage were matched on parity and gestational day of serum sampling with 204 delivering women. In a multiple logistic regression with adjustment for age, BMI, parity and gestational age at serum sampling, women with the highest tertile of exposure to perfluorononanoic acid (PFNA) and perfluorodecanoic acid (PFDA) in pregnancy had odds ratios for miscarriage of 16.5 (95% CI 7.4-36.6-36.5) and 2.67 (1.31-5.44), respectively, as compared to the lowest tertile. In the matched data set, the OR were 37.9 (9.9-145.2) and 3.71 (1.60-8.60), respectively. The association with perfluorohexane sulfonic acid (PFHxS) was in the same direction, but not statistically significant, while no association was found with PFOA and PFOS. Our findings require confirmation due to the possible public health importance, given that all pregnant women are exposed to these widely used compounds.
Human milk plays a critical role in infant development and health, particularly in cognitive, immune, and cardiometabolic functions. Milk contains extracellular vesicles (EVs) that can transport ...biologically relevant cargo from mother to infant, including microRNAs (miRNAs). We aimed to characterize milk EV-miRNA profiles in a human population cohort, assess potential pathways and ontology, and investigate associations with maternal characteristics. We conducted the first study to describe the EV miRNA profile of human milk in 364 mothers from a population-based mother-infant cohort in the Faroe Islands using small RNA sequencing. We detected 1523 miRNAs with ≥ one read in 70% of samples. Using hierarchical clustering, we determined five EV-miRNA clusters, the top three consisting of 15, 27 and 67 miRNAs. Correlation coefficients indicated that the expression of many miRNAs within the top three clusters was highly correlated. Top-cluster human milk EV-miRNAs were involved in pathways enriched for the endocrine system, cellular community, neurodevelopment, and cancers. miRNA expression was associated with time to milk collection post-delivery, maternal body mass index, and maternal smoking, but not maternal parity. Future studies investigating determinants of human EV-miRNAs and associated health outcomes are needed to elucidate the role of human milk EV-miRNAs in health and disease.
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•Prenatal pollutant exposures do not influence expression of individual EV-miRNAs.•Sparse principal components analysis selected 158 EV-miRNAs in the first 4 PCs.•Mercury was ...associated with 13 miRNAs in PC1 and 7 miRNAs in PC3.•Polychlorinated biphenyls were associated with 3 miRNAs in PC2.•Perfluoroalkyl substances were associated with miRNAs in PC4.
Early life exposures to marine contaminants can adversely impact child health but modes of action are unclear. Human milk contains extracellular vesicles (EVs) that can transport biologically relevant cargo from mother to infant, including microRNAs (miRNAs), and may partly mediate the effects of pollutants on child health. However, the role of marine pollutants on miRNA expression in milk EVs is unexplored.
We isolated EV RNA from 333 milk samples collected between 2 and 74 days postpartum from a Faroese birth cohort born 1997–2000 and sequenced 2083 miRNAs using a targeted library preparation method. We quantified five perfluoroalkyl substances (PFAS), pesticide metabolite p,p’-dichlorodiphenyldichloroethylene (DDE), and the sum of three major polychlorinated biphenyls (ΣPCBs) in maternal serum at 34 weeks of gestation and maternal hair total mercury (Hg) at birth. We used negative binomial regressions to estimate associations between individual pollutants and 418 reliably expressed EV-miRNAs adjusted for potential confounders. We performed sparse principal components (PCs) analysis to derive the first four components of the EV-miRNA data and examined associations between pollutants and PCs using Bayesian kernel machine regression (BKMR).
We observed no associations between pollutants and individual EV-miRNA expression after controlling the false discovery rate at 0.1. However, BKMR suggested that Hg was positively associated with PC1 and negatively associated with PC3, while ΣPCBs was negatively associated with PC3, and two PFAS were associated with PC4. Exploration of PC loadings followed by pathway analyses suggested that miRNAs in PC1 (miR-200b-3p, miR-664a-3p, miR-6738-5p, miR-429, miR-1236-5p, miR-4464, and miR-30b-5p) may be related to Hg neurotoxicity, while remaining PCs require further research.
Our findings suggest that groups of milk EV-miRNAs may better serve as environmental biomarkers than individual miRNAs. Future studies are needed to elucidate the role of milk EV-miRNAs in child health following prenatal exposures.
Stored toenail clippings were used to assess mercury exposure in men and women who had had incident cardiovascular events and in matched controls. Participants with higher mercury exposures did not ...have a higher risk of cardiovascular events, even after adjustment for fish consumption.
Controversy has arisen over the risks and benefits of fish consumption in adults. Fish intake is inversely associated with the risk of coronary heart disease, especially fatal coronary heart disease, and ischemic stroke.
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Fish are also the major source of exposure to methylmercury.
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Chronic, low-level methylmercury exposure appears to cause subtle but measurable neurodevelopmental delay in infants, and it is recommended that women of childbearing age, pregnant or nursing mothers, and infants and young children eat no more than two servings of fish per week and also limit their intake of selected species of fish that are especially high . . .
OBJECTIVE: Vitamin D deficiency is thought to be a risk factor for development of type 2 diabetes, and elderly subjects at northern latitudes may therefore be at particular risk. RESEARCH DESIGN AND ...METHODS: Vitamin D status was assessed from serum concentrations of 25-hydroxyvitamin D₃ 25(OH)D₃ in 668 Faroese residents aged 70-74 years (64% of eligible population). We determined type 2 diabetes prevalence from past medical histories, fasting plasma concentrations of glucose, and/or glycosylated hemoglobin (HbA₁c). RESULTS: We observed 70 (11%) new type 2 diabetic subjects, whereas 88 (13%) were previously diagnosed. Having vitamin D status <50 nmol/L doubled the risk of newly diagnosed type 2 diabetes after adjustment for BMI, sex, exposure to polychlorinated biphenyls, serum triacylglyceride concentration, serum HDL concentration, smoking status, and month of blood sampling. Furthermore, the HbA₁c concentration decreased at higher serum 25(OH)D₃ concentrations independent of covariates. CONCLUSIONS: In elderly subjects, vitamin D sufficiency may provide protection against type 2 diabetes. Because the study is cross-sectional, intervention studies are needed to elucidate whether vitamin D could be used to prevent development of type 2 diabetes.
Humans are exposed to poly- and perfluoroalkyl substances (PFASs) from diverse sources and this has been associated with negative health impacts. Advances in analytical methods have enabled routine ...detection of more than 15 PFASs in human sera, allowing better profiling of PFAS exposures. The composition of PFASs in human sera reflects the complexity of exposure sources but source identification can be confounded by differences in toxicokinetics affecting uptake, distribution, and elimination. Common PFASs, such as perfluorooctanoic acid (PFOA), perfluorooctane sulfonic acid (PFOS) and their precursors are ubiquitous in multiple exposure sources. However, their composition varies among sources, which may impact associated adverse health effects.
We use available PFAS concentrations from several demographic groups in a North Atlantic seafood consuming population (Faroe Islands) to explore whether chemical fingerprints in human sera provide insights into predominant exposure sources. We compare serum PFAS profiles from Faroese individuals to other North American populations to investigate commonalities in potential exposure sources. We compare individuals with similar demographic and physiological characteristics and samples from the same years to reduce confounding by toxicokinetic differences and changing environmental releases.
Using principal components analysis (PCA) confirmed by hierarchical clustering, we assess variability in serum PFAS concentrations across three Faroese groups. The first principal component (PC)/cluster consists of C9-C12 perfluoroalkyl carboxylates (PFCAs) and is consistent with measured PFAS profiles in consumed seafood. The second PC/cluster includes perfluorohexanesulfonic acid (PFHxS) and the PFOS precursor N-ethyl perfluorooctane sulfonamidoacetate (N-EtFOSAA), which are directly used or metabolized from fluorochemicals in consumer products such as carpet and food packaging. We find that the same compounds are associated with the same exposure sources in two North American populations, suggesting generalizability of results from the Faroese population.
We conclude that PFAS homologue profiles in serum provide valuable information on major exposure sources. It is essential to compare samples collected at similar time periods and to correct for demographic groups that are highly affected by differences in physiological processes (e.g., pregnancy). Information on PFAS homologue profiles is crucial for attributing adverse health effects to the proper mixtures or individual PFASs.
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