Numerous ubiquitous environmental chemicals are established or suspected neurotoxicants, and infants are exposed to a mixture of these during the critical period of brain maturation. However, ...evidence for associations with the risk of attention-deficit/hyperactivity disorder (ADHD) is sparse. We investigated early-life chemical exposures in relation to ADHD.
We used a birth cohort of 2606 Norwegian mother–child pairs enrolled 2002–2009 (HUMIS), and studied a subset of 1199 pairs oversampled for child neurodevelopmental outcomes. Concentrations of 27 persistent organic pollutants (14 polychlorinated biphenyls, 5 organochlorine pesticides, 6 brominated flame retardants, and 2 perfluoroalkyl substances) were measured in breast milk, reflecting the child's early-life exposures. We estimated postnatal exposures in the first 2 years of life using a pharmacokinetic model. Fifty-five children had a clinical diagnosis of ADHD (hyperkinetic disorder) by 2016, at a median age of 13 years. We used elastic net penalized logistic regression models to identify associations while adjusting for co-exposure confounding, and subsequently used multivariable logistic regression models to obtain effect estimates for the selected exposures.
Breast milk concentrations of perfluorooctane sulfonate (PFOS) and β‑hexachlorocyclohexane (β-HCH) were associated with increased odds of ADHD: odds ratio (OR) = 1.77, 95% confidence interval (CI): 1.16, 2.72 and OR = 1.75, 95% CI: 1.22, 2.53, per interquartile range increase in ln-transformed concentrations, respectively. Stronger associations were observed among girls than boys for PFOS (pinteraction = 0.025). p,p′‑Dichlorodiphenyltrichloroethane (p,p′-DDT) levels were associated with lower odds of ADHD (OR = 0.64, 95% CI: 0.42, 0.97). Hexachlorobenzene (HCB) had a non-linear association with ADHD, with increasing risk in the low-level exposure range that switched to a decreasing risk at concentrations above 8 ng/g lipid. Postnatal exposures showed similar results, whereas effect estimates for other chemicals were weaker and imprecise.
In a multi-pollutant analysis of four classes of chemicals, early-life exposure to β-HCH and PFOS was associated with increased risk of ADHD, with suggestion of sex-specific effects for PFOS. The unexpected inverse associations between p,p′-DDT and higher HCB levels and ADHD could be due to live birth bias; alternatively, results may be due to chance findings.
•We assessed associations between early-life exposure to 27 contaminants and doctor-diagnosed ADHD in school-age children•Odds of ADHD increased 75% per interquartile range increase in β-HCH levels•Odds of ADHD increased 77% per interquartile range increase in PFOS levels, with higher odds in girls than boys•p,p′-DDT was associated with lower odds of ADHD while HCB had a non-linear exposure–response
This study presents four years ambient monitoring data of seventeen 2,3,7,8-chlorine substituted polychlorinated dibenzo-p-dioxins and polychlorinated dibenzofurans (PCDD/Fs), twelve dioxin-like ...polychlorinated biphenyls (dl-PCBs) and sixteen polycyclic aromatic hydrocarbons (PAHs) designed by the US EPA at a background site in central Europe during 2011–2014. The concentrations expressed as toxic equivalents (TEQs) using the WHO2005-scheme for PCDD/Fs (0.2 fg m−3-61.1 fg m−3) were higher than for dl-PCBs (0.01 fg m−3-2.9 fg m−3), while the opposite was found in terms of mass concentrations. ΣPAHs ranged from 0.20 ng m−3 to 134 ng m−3. The mass concentration profile of PCDD/Fs, dl-PCBs and PAHs was similar throughout the four years. PCDD/Fs and PAHs concentrations were dominated by primary sources peaking in winter, while those of dl-PCBs were controlled by secondary sources characterized by a spring-summer peak. During 2011–2014, no significant decrease in the atmospheric levels of ΣPCDD/Fs was observed. On the other hand, the concentrations of Σdl-PCBs and ΣPAHs were decreasing, with halving times of 5.7 and 2.7 years, respectively. We estimated that 422 pg m−2 year−1-567 pg m−2 year−1 TEQ PCDD/Fs and 3.48 pg m−2 year−1-15.8 pg m−2 year−1 TEQ dl-PCBs were transferred from the air to the ground surfaces via dry particulate deposition during 2011–2014.
Display omitted
•PCDD/Fs and PAHs concentrations were dominated by primary sources.•dl-PCBs concentrations were dominated by secondary sources.•No significant decrease in the atmospheric levels of ΣPCDD/Fs during 2011–2014.
In this study, 10 polybrominated diphenyl ethers (PBDEs) and 19 alternative halogenated flame retardants (AFRs) were determined in >450 human milk samples across three European countries, ...representing northern, western and eastern Europe. This study provides first insights into the occurrence of selected AFRs in mother milk samples and compares them among three European countries. Sums of median concentrations of the most frequently detected PBDEs were 2.16, 0.88 and 0.45ngg−1 lipid weight (lw) in Norway, the Netherlands and Slovakia, respectively. The sum of the concentrations of AFRs ranged from 0.14 to 0.25ngg−1lw in all countries, which was 2 to 15 times less compared to Σ7PBDEs. The Penta-BDE replacement, bis(2-ethylhexyl) tetrabromophthalate, BEH-TEBP, was present at the greatest concentrations of any of the AFRs and in some samples exceeded concentrations of BDE 47 and BDE 153. Four AFRs including bromobenzenes (hexabromobenzene, pentabromobenzene, pentabromotoluene) and another Penta-BDE replacement (2-ethylhexyl-2,3,4,5-tetrabromobenzoate, EH-TBB) were detected in >42% of all human milk samples. Because of the potential developmental neurotoxicity of the halogenated flame retardants, infant dietary intakes via breastfeeding were estimated; in four cases the intakes of BDE 47 exceeded the reference dose indicating that the present concentrations may pose a risk for children.
Display omitted
•Legacy and alternative flame retardants were determined in human milk in Europe.•The median sum of PBDEs was 2–15 times higher than the median of alternative FRs.•BEH-TEBP was present at high concentrations in milk samples.•Uptake with milk was found to be the main exposure source for infants.
•In vitro and in vivo interactive effects of n-TiO2 and TCDD are reported in mussel.•Both synergistic and antagonistic effects were observed on a wide range of biomarkers.•Exposure to of ...n-TiO2increased TCDD accumulation, indicating a Trojan horse effect.
Despite the growing concern over the potential biological impact of nanoparticles (NPs) in the aquatic environment, little is known about their interactions with other pollutants. The bivalve Mytilus sp, largely utilized as a sentinel for marine contamination, has been shown to represent a significant target for different types of NP, including n-TiO2, one of the most widespread in use. In this work, the possible interactive effects of n-TiO2 and 2,3,7,8-TCDD, chosen as models of NP and organic contaminant, respectively, were investigated in Mytilus galloprovincialis. In vitro experiments with n-TiO2 and TCDD, alone and in combination, were carried out in different conditions (concentrations and times of exposure), depending on the target (hemocytes, gill cells and biopsies) and the endpoint measured. Mussels were also exposed in vivo to n-TiO2 (100μgL−1) or to TCDD (0.25μgL−1), alone and in combination, for 96h. A wide range of biomarkers, from molecular to tissue level, were measured: lysosomal membrane stability and phagocytosis in hemocytes, ATP-binding cassette efflux transporters in gills (gene transcription and efflux activity), several biomarkers of genotoxicity in gill and digestive cells (DNA damage, random amplified polymorphic DNA-RAPD changes), lysosomal biomarkers and transcription of selected genes in the digestive gland. The results demonstrate that n-TiO2 and TCDD can exert synergistic or antagonistic effects, depending on experimental condition, cell/tissue and type of measured response. Some of these interactions may result from a significant increase in TCDD accumulation in whole mussel organisms in the presence of n-TiO2, indicating a Trojan horse effect. The results represent the most extensive data obtained so far on the sub-lethal effects of NPs and organic contaminants in aquatic organisms. Moreover, these data extend the knowledge on the molecular and cellular targets of NPs in bivalves.
Pine needles were sampled to determine levels of polychlorinated dibenzo-p-dioxins and dibenzofurans (PCDD/Fs) and metals in Scots pine (Pinus sylvestris) needles at industrial, urban and background ...sites in Sweden (SW), Czech Republic (CZ) and Slovakia (SK). Spatial and temporal patterns of PCDD/Fs in pine needles were investigated and principal component analysis (PCA) used to determine spatial patterns, potential sources and transport of PCDD/Fs. Levels of PCDD/Fs in pine needles were generally greatest near to industrial sites (Ʃ2,3,7,8-PCDD/Fs (lower bound (LB)): 6 ng kg−1 – 190 ng kg−1) compared to urban and background sites (Ʃ2,3,7,8-PCDD/Fs (LB): 0.90 ng kg−1 – 20 ng kg−1). Using metal contamination in pine needles helped to detect spatial patterns and separate local thermal sources of PCDD/Fs.
•Levels of dioxins were determined in pine needles in 3 different European countries.•Land use influences the spatial pattern of PCDD/F levels and profiles in needles.•Atmospheric level/seasonal uptake influence temporal PCDD/F levels in needles.•PCDD/F profile and principal component analysis were used to identify sources.•Metal markers/profiles in needles aided in distinguishing PCDD/F thermal sources.
: Immune system development, particularly in the prenatal period, has far‐reaching consequences for health during early childhood, as well as throughout life. Environmental disturbance of the ...complex balances of Th1 and Th2 response mechanisms can alter that normal development. Dysregulation of this process or an aberrant trajectory or timing of events can result in atopy, asthma, a compromised ability to ward off infection, or other auto‐immune disease. A wide range of chemical, physical and biological agents appear to be capable of disrupting immune development. This MiniReview briefly reviews developmental milestones of the immune system in the prenatal period and early life, and then presents examples of environmentally induced alterations in immune markers. The first example involves a birth cohort study linked to an extensive programme of air pollution monitoring; the analysis shows prenatal ambient polycyclic aromatic hydrocarbons (PAH) and fine particle (PM2.5) exposures to be associated with altered lymphocyte immunophenotypic distributions in cord blood and possible changes in cord serum immunoglobulin E levels. The second example is a study of prenatal‐polychlorinated biphenyl (PCB) exposures and the foetal development of the thymus, the organ responsible for lymphocyte maturation. Mothers with higher serum concentrations of PCBs gave birth to neonates having smaller indices of thymus size. Finally, this report underscores the tight connection between development of the immune system and that of the central nervous system, and the plausibility that disruption of critical events in immune development may play a role in neurobehavioural disorders.
Polychlorinated biphenyls (PCBs) are ubiquitous environmental toxins. Although there is growing evidence to support an association between PCBs and deficits of neurodevelopment, the specific ...mechanisms are not well understood. The potentially different roles of specific PCB groups defined by chemical structures or hormonal activities e.g., dioxin-like, non-dioxin like, or anti-estrogenic PCBs, remain unclear. Our objective was to examine the association between prenatal exposure to defined subsets of PCBs and neurodevelopment in a cohort of infants in eastern Slovakia enrolled at birth in 2002-2004.
Maternal and cord serum samples were collected at delivery, and analyzed for PCBs using high-resolution gas chromatography. The Bayley Scales of Infant Development -II (BSID) were administered at 16 months of age to over 750 children who also had prenatal PCB measurements.
Based on final multivariate-adjusted linear regression model, maternal mono-ortho-substituted PCBs were significantly associated with lower scores on both the psychomotor (PDI) and mental development indices (MDI). Also a significant association between cord mono-ortho-substituted PCBs and reduced PDI was observed, but the association with MDI was marginal (p = 0.05). Anti-estrogenic and di-ortho-substituted PCBs did not show any statistically significant association with cognitive scores, but a suggestive association between di-ortho-substituted PCBs measured in cord serum and poorer PDI was observed.
Children with higher prenatal mono-ortho-substituted PCB exposures performed more poorly on the Bayley Scales. Evidence from this and other studies suggests that prenatal dioxin-like PCB exposure, including mono-ortho congeners, may interfere with brain development in utero. Non-dioxin-like di-ortho-substituted PCBs require further investigation.
► Comprehensive study of mother’s exposure to toxic pollutants in Slovakia. ► PBDE levels measured for the first time in Slovak breast milk. ► Intakes of PCDDs/Fs and dl-PCBs for infants exceed the ...tolerable intake set by WHO.
The concentrations of polychlorinated dibenzo-p-dioxins (PCDDs), polychlorinated dibenzofurans (PCDFs), dioxin-like polychlorinated biphenyls (dl-PCBs) and polybrominated diphenylethers (PBDEs) in 33 breast milk samples collected in 2006–2007 from primipara mothers close to four industrial areas of Slovak Republic were determined. The total PCDDs/PCDFs and dl-PCBs expressed as TEQ based on WHO TEFs 1998 in breast milk samples varied from 5.0 to 51.8
pg
g
−1 fat (median: 13.1
pg
g
−1 fat; mean: 18.0
pg
g
−1 fat). The measurements of seven PBDE congeners (IUPAC No. 28, 47, 99, 100, 153, 154, and 183) were performed for the first time in human milk from Slovakia. PBDE levels ranged between 0.22 and 1.62
ng
g
−1 fat, with median and mean value of 0.43
ng
g
−1 fat and 0.57
ng
g
−1 fat respectively. No statistically significant differences were observed between studied areas in total PBDE concentrations.
Furthermore, this study presents first results concerning the daily intake (DI) of PCDDs/PCDFs and dioxin-like compounds for the most vulnerable breast-fed infant population in Slovakia. The total PCDD/PCDF and dl-PCB DI for an infant during the first 2
months of life was estimated in a range from 14.4 to 230
pg
TEQ
kg
−1
b.w., with a median value of 58.9
pg
TEQ
kg
−1
b.w.. The DI values substantially exceeded the tolerable daily intake (TDI) 1–4
pg
TEQ
kg
−1
b.w. recommended by WHO. The dietary infant intake concerning PBDEs was estimated to be between 0.69 and 7.1
ng
kg
−1
b.w.
d
−1, with median value of 1.7
ng
kg
−1
b.w.
d
−1.
Evidence of associations of pre- and postnatal exposure to polychlorinated biphenyls (PCBs) with cognitive development beyond early childhood is inconsistent. A previous report from this cohort ...observed adverse associations between early life PCB exposures and infant Bayley scores at age 16 months. The present study examines pre- and postnatal PCB exposures in relation to both behavior and cognitive development at age 45 months. Participants were 472 mother-child pairs residing in an area of eastern Slovakia characterized by environmental contamination with PCBs, which resulted in elevated blood serum concentrations. PCB-153 and PCB-118 concentrations were measured in maternal and in infant 6-, 16-, and 45-month serum samples. At age 45 months, children were administered five subtests of the Wechsler Preschool and Primary Scale of Intelligence (WPPSI-III), and mothers completed the Child Behavior Checklist (CBCL). Negative binomial and multiple linear regressions were used to estimate PCB—CBCL and PCB—WPPSI-III subtest score associations, respectively. Pre- and postnatal levels of PCB-153 and PCB-118 were not associated with cognitive performance on the WPPSI-III in this cohort. There was some suggestion that higher postnatal PCB concentrations were associated with more sleep problems and feelings of depression and anxiousness.
Display omitted
•Prenatal PCB-associated cognitive deficits are generally well-documented.•There is mixed evidence as to whether these effects persist into childhood.•This association was examined in a cohort with varied PCB exposures.•Evidence of an adverse association was not observed in this study.
Background: Hydroxylated polychlorinated biphenyls (OH-PCBs), unlike PCBs, are in general readily excreted yet are still detected in humans and animals. Active transport of OH-PCBs across the ...placenta and hydroxylation of PCBs by the fetus suggest the potential for greater impact on the fetus compared with the parent PCB compounds, but little is known about their health effects, particularly in humans. Objectives: The objective of this study was to evaluate the associations between prenatal OH-PCB exposure and neurodevelopment in children at 16 months of age in eastern Slovakia. Methods: A birth cohort (n = 1,134) was enrolled during 2002-2004. We analyzed six OH-PCB metabolites (4-OH-CB-107, 3-OH-CB-153, 4-OH-CB-146, 3-OH-CB-138, 4-OH-CB-187, and 4-OH-CB-172) in a subset of the cohort. The Bayley Scales of Infant Development were administered to the children at the 16-month follow-up visit. We developed multiple linear regression models predicting standardized scores for the Mental Development Index (MDI) and Psychomotor Development Index (PDI) from maternal (n = 147) and cord (n = 80) serum OH-PCB concentrations, adjusting for sex of child, district, HOME (Home Observation for Measurement of the Environment) score, and maternal score on Raven's Progressive Matrices. Results: Cord 4-OH-CB-107 was significantly associated with lower MDI (ß = -2.27; p = 0.01) and PDI (ß = -4.50; p = 0.004). Also, maternal 4-OH-CB-107 was significantly associated with lower MDI (ß = -1.76; p = 0.03) but not PDI. No other OH-PCB metabolites were associated with decreased PDI or MDI. Conclusions: Our findings showed a significant association of 4-OH-CB-107 with decreased MDI, which can possibly be mediated by endocrine disruption, altered neurotransmitter functions, or reduced thyroid hormone concentrations in brain.
PDF
