Some experimental and human data suggest that exposure to polychlorinated biphenyls (PCBs) may induce ototoxicity, though results of previous epidemiologic studies are mixed and generally focus on ...either prenatal or postnatal PCB concentrations exclusively.
Our aim was to evaluate the association between pre- and postnatal PCB concentrations in relation to cochlear status, assessed by distortion product otoacoustic emissions (DPOAEs), and to further clarify the critical periods in development where cochlear status may be most susceptible to PCBs.
A total of 351 children from a birth cohort in eastern Slovakia underwent otoacoustic testing at 45 months of age. Maternal pregnancy, cord, and child 6-, 16-, and 45-month blood samples were collected and analyzed for PCB concentrations. At 45 months of age, DPOAEs were assessed at 11 frequencies in both ears. Multivariate, generalized linear models were used to estimate the associations between PCB concentrations at different ages and DPOAEs, adjusting for potential confounders.
Maternal and cord PCB-153 concentrations were not associated with DPOAEs at 45 months. Higher postnatal PCB concentrations at 6-, 16-, and 45-months of age were associated with lower (poorer) DPOAE amplitudes. When all postnatal PCB exposures were considered as an area-under-the-curve metric, an increase in PCB-153 concentration from the 25th to the 75th percentile was associated with a 1.6-dB SPL (sound pressure level) decrease in DPOAE amplitude (95% CI: -2.6, -0.5; p = 0.003).
In this study, postnatal rather than maternal or cord PCB concentrations were associated with poorer performance on otoacoustic tests at age 45 months.
Perfluoroalkyl substances (PFASs) are man-made fluorinated compounds with endocrine-disrupting properties, detected in 99% of serum samples worldwide and associated with adverse childhood health ...outcomes. The aim of this study was to describe determinants of prenatal exposure to PFASs in Slovakia.
This study was based on Slovak multicentric prospective mother-child cohort PRENATAL (N = 796). Cord blood samples were collected within 2010–2012 and PFASs were analyzed in a subpopulation of 322 newborns. Concentrations of perfluorooctane sulfonic acid (PFOS), perfluorohexane sulfonic acid (PFHxS), perfluorooctanoic acid (PFOA) and perfluorononanoic acid (PFNA) were measured in the samples of cord blood using an ultrahigh-performance liquid chromatography- mass spectrometry (U-HPLC−MS) method. From questionnaires, we obtained information on medical history of mother, socio-demographic factors, nutrition and environmental factors. Association between maternal characteristics and PFASs exposure was analyzed using multivariable linear regression models.
The highest cord blood concentration (geometric mean ± SD) was observed for PFOA (0.79 ± 2.21 ng/ml) followed by PFOS (0.36 ± 2.56 ng/ml), PFNA (0.20 ± 2.44 ng/ml) and PFHxS (0.07 ± 2.36 ng/ml). Primiparity was associated with higher levels of all four PFAS: PFOS (exp. β = 1.25; 95%CI1.03; 1.53), PFOA (exp. β = 1.49; 95%CI1.18; 1.89), PFNA (exp. β = 1.30; 95%CI1.05; 1.60) and PFHxS (exp. β = 1.49; 95%CI 1.20; 1.86). In addition, maternal age category 29 years and more was associated with higher PFNA and PFHxS levels (exp. β = 1.27; 95%CI1.04; 1.55 and exp. β = 1.30; 95%CI1.06; 1.60, respectively) and higher educational level of mother was associated with higher PFNA levels (exp. β = 1.32; 95%CI1.04; 1.68). Higher fish consumption was associated with lower PFNA levels (exp. β = 0.49; 95%CI0.26; 0.92).
We observed that PFASs cord blood concentrations were comparable or lower than those measured in western or northern European countries. We identified parity as the main determinant of PFASs exposure in our population and maternal age and education as factors that might be associated with exposure to certain PFASs.
•The highest mean cord blood concentration was observed for PFOA.•This study points out parity as the main determinant of PFASs exposure in our population.•PFNA levels in cord blood were associated with higher educational level of mother.•PFNA and PFHxS in cord blood were associated with maternal age.
Toxic equivalency factors (TEFs) are an important component in the risk assessment of dioxin-like human exposures. At present, this concept is based mainly on in vivo animal experiments using oral ...dosage. Consequently, the current human TEFs derived from mammalian experiments are applicable only for exposure situations in which oral ingestion occurs. Nevertheless, these "intake" TEFs are commonly-but incorrectly-used by regulatory authorities to calculate "systemic" toxic equivalents (TEQs) based on human blood and tissue concentrations, which are used as biomarkers for either exposure or effect.
We sought to determine relative effect potencies (REPs) for systemic human concentrations of dioxin-like mixture components using thyroid volume or serum free thyroxine (FT4) concentration as the outcomes of interest.
We used a benchmark concentration and a regression-based approach to compare the strength of association between each dioxin-like compound and the thyroid end points in 320 adults residing in an organochlorine-polluted area of eastern Slovakia.
REPs calculated from thyroid volume and FT4 were similar. The regression coefficient (β)-derived REP data from thyroid volume and FT4 level were correlated with the World Health Organization (WHO) TEF values (Spearman r = 0.69, p = 0.01 and r = 0.62, p = 0.03, respectively). The calculated REPs were mostly within the minimum and maximum values for in vivo REPs derived by other investigators.
Our REPs calculated from thyroid end points realistically reflect human exposure scenarios because they are based on chronic, low-dose human exposures and on biomarkers reflecting body burden. Compared with previous results, our REPs suggest higher sensitivity to the effects of dioxin-like compounds.
Polybrominated diphenylethers (PBDEs) are persistent organic pollutants (POPs), they are considered endocrine disruptors and can bioaccumulate in nature, and in living tissue. Human exposure to and ...the presence of PBDEs in human samples is of concern due to their potential health risks. Young children are one of the most vulnerable populations to PBDE's potential health effects.
Ninety-one serum samples of 6-year-old children, residing in a contaminated location, due to former production of polychlorinated biphenyls (PCBs), were analysed to examine children's exposure to PBDEs in Slovakia. Median serum concentrations found for individual PBDE congeners BDE-28+33, −47, −99, −100, −153, −154 and −183 were 0.015, 0.184, 0.079, 0.046, 0.176, 0.014, and 0.097 ng g−1 lipid weight, respectively.
Children's preschool maturity was measured using the Wechsler Preschool and Primary Scale of Intelligence (WPPSI-III) test. In multivariate analyses BDE-153 serum concentrations were significantly inversely associated with WPPSI-III composite score (p = 0.011, β = −23.6), while adjusting for PCB-153 and sex. Significant negative associations were observed for BDE-153 serum concentrations (p = 0.002, β = −29.8) and WPPSI-III composite score, after controlling for PCB-118 and sex. Negative associations were also observed for BDE-47, BDE-100 and BDE-153, with different individual WPPSI subtest scores, after adjustment with PCB-153 and/or PCB-118 and sex. Serum concentrations of PCB-153 and PCB-118 were not statistically significantly associated with WPPSI-III composite score and individual subtest scores. These findings demonstrate adverse effects of PBDE serum exposure on preschool maturity of children, and PBDEs potentially negative impact on child neuropsychological development.
•PBDE serum concentrations in children from Slovakia.•BDE-47 and BDE-153 were the most abundant congeners.•Negative associations observed between PBDE serum concentrations and preschool maturity of children using the WPPSI test.•No associations between PCBs and preschool maturity tests.•Adverse effect of PBDEs on neuropsychological development of children.
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.
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•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.
We evaluated concentrations of 15 PCB congeners in blood serum of 2047 adults, 431 8–9-year old children and 1134 mother-child pairs born in 2001–2003. These subjects were long-standing residents ...living up to 70 km (to the north) and up to 50 km (to the south) of the former Chemko Strážske PCB production facility in the Michalovce district of Slovakia. We plotted serum concentration against distance from the plant both with and without consideration of the direction of their homes from the site. The decrease in exposure with distance could be described by an exponential function which was dependent on direction and climatic parameters. By kriging we created maps depicting predicted isoconcentration contours for sex- and age-adjusted serum concentration of ∑PCBs for the same group of children, adults and mothers. The principle of our risk analysis was to relate serum concentration data, reflecting PCB body burden, using the critical concentrations established by the French Agency for Food, Environmental and Occupational Health & Safety (ANSES 2010) as thresholds below which the probability of effects on health is regarded as negligible. We conclude that 10 years ago, around 200,000 residents were at risk in this densely populated area. Exposure has since decreased but the mechanism for this has not yet been studied.
The aim was to characterize placental transfer of some congeners of polychlorinated biphenyls (PCBs) and to relate human in utero exposure to these pollutants to their physicochemical properties. We ...included into the study 1134 births during the period 2002–2003 from two highly PCB contaminated districts in eastern Slovakia. Concentrations of 15 PCB congeners (IUPAC No. 28, 52, 101, 123+149, 118, 114, 153, 105, 138+163, 167, 156+171, 157, 180, 170, and 189) in umbilical cord (C) and maternal serum (M) were determined. The C/M ratios were significantly related, either positively or inversely depending on parameter, to the logarithm of partition coefficient octanol–water (KOW), to fusion enthalpy at the melting point, molecular weight, water solubility, total surface area of the molecule, solvent accessible surface area, melting point, molar volume, and molecular electronegativity distance vector. We found an inverse association between logKOW and lipid adjusted logC/M (const=1.078, b1=−0.179, p<0.001, R2=0.039). Parameters evaluated were interrelated except fusion enthalpy at the melting point and electron affinity vs. solubility. We discuss the possible role of cholesterol as a transplacental transporter of PCBs.
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.
Experimental evidence from animals indicates that exposure to polychlorinated biphenyls (PCBs) causes deterioration of the outer hair cells (OHCs) of the cochlea. To test this hypothesis in humans, ...we measured serum PCB concentrations in 574 12-year-old children residing in three districts in the Slovak Republic using high-resolution gas chromatography with microelectron capture detection. As a marker of cochlear status, we measured transient evoked (TE) and distortion product (DP) otoacoustic emissions (OAEs), and assessed the cross-sectional association between serum PCBs and OAEs. Median total PCB concentrations were 352.8, 150.5, and 134.9 ng/g lipid in Michalovce, Svidnik, and Bratislava, respectively. In multivariate regression models where otoacoustic measures were modeled as a function of log (base 10) PCB concentrations with adjustment for gender, age, and site of examination, dioxin-like PCBs, nondioxin-like PCBs and a PCB grouping targeting upregulation of hepatic uridine 5'-diphospho-glucuronosyltransferase were significantly associated with lower TEOAE powers at 1000 and 1500 Hz. At 1500 Hz, we observed a strong association with sum of PCBs and DL-PCBs, in the left ear only. The DPOAEs at 1000 Hz were associated with all four PCB groupings. The results of this study show that PCBs may affect the OHCs of the cochlea, a result consistent with findings from animal studies published to date.
The aim of this study was to examine the hypothesis that organochlorine pesticides (OCPs), hexachlorobenzene (HCB), β-hexachlorocyclohexane (β-HCH), and 1,1,1-trichloro-2,2-bis(4-chlorophenyl)ethane ...(p,p′-DDT) and its metabolite 1,1-dichloro-2,2-bis(4-chlorophenyl)ethylene (p,p′- DDE) are ototoxic to humans. A multivariate general linear model was designed, in which the statistical relation between blood serum concentrations of HCB, β-HCH, p,p′-DDT, or p,p′-DDE at different ages (at birth, 6, 16, and 45 months) and the distortion product otoacoustic emissions (DPOAEs) was treated as multivariate outcome variables. Polychlorinated biphenyl (PCB) congeners and OCPs were strongly correlated in serum of children from our cohort. To ascertain that the association between DPOAEs at a given frequency and concentration of a pesticide is not influenced by PCBs or other OCP also present in serum, we calculated benchmark concentrations (BMCs) relating DPOAEs to a serum pesticide alone and in presence of confounding PCB-153 or other OCPs. We found that BMCs relating DPOAEs to serum pesticides are not affected by confounders. DPOAE amplitudes were associated with serum OCPs at all investigated time intervals, however, in a positive way with prenatal exposure and in a negative way with all postnatal exposures. We observed tonotopicity in the association of pesticides with amplitude of DPOAEs as its strength was frequency dependent. We conclude that exposure to OCPs in infancy at environmental concentrations may be associated with hearing deficits.
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