Publications by authors named "Tomáš Trnovec"

79 Publications

Targeted and suspect screening of plasticizers in house dust to assess cumulative human exposure risk.

Sci Total Environ 2021 Aug 23;781:146667. Epub 2021 Mar 23.

RECETOX, Masaryk University, Kamenice 753/5, pavilion D29, 625 00 Brno, Czech Republic.

Indoor dust is an important exposure route to anthropogenic chemicals used in consumer products. Plasticizers are common product additives and can easily leach out of the product and partition to dust. Investigations of plasticizers typically focus on a subset of phthalate esters (PEs), but there are many more PEs in use, and alternative plasticizers (APs) are seeing greater use after recognition of adverse health effects of PEs. In this study we use full scan high resolution mass spectrometry for targeted and suspect screening of PEs and APs in house dust and to assess the potential risk of human exposure. House dust samples from Eastern Slovakia were investigated and concentrations of ∑PEs and ∑APs ranged 12-2765 μg/g and 45-13,260 μg/g, respectively. APs were at similar levels to PEs, indicating common usage of these compounds in products in homes. Evaluation of individual compound toxicity combined with human intake via dust ingestion suggested PEs are of lower priority compared to semivolatile organic compounds such as polychlorinated biphenyls due to their lower toxicity. However, cumulative risk assessment (CRA) is a more appropriate evaluation of risk, considering the presences of many PEs in dust and their similar toxic mode of action. CRA based on median toxicity reference values (TRVs) suggested acceptable risks for dust ingestion, however, the wide range of literature-derived TRVs is a large uncertainty, especially for the APs. Use of newer TRVs suggest risk from dust ingestion alone, i.e. not even considering diet, inhalation, and dermal contact. Additionally, screening of full-scan instrumental spectra identified a further 40 suspect PE compounds, suggesting the CRA based on the 12 target PEs underestimates the risk.
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http://dx.doi.org/10.1016/j.scitotenv.2021.146667DOI Listing
August 2021

Biomarkers of metabolic disorders and neurobehavioral diseases in a PCB- exposed population: What we learned and the implications for future research.

Environ Res 2020 12 13;191:110211. Epub 2020 Sep 13.

Department of Pediatrics and Child Health, College of Medicine, Howard University, Washington DC, USA; Department of Biology, Howard University, Washington, DC, USA. Electronic address:

Polychlorinated biphenyls (PCBs) are one of the original twelve classes of toxic chemicals covered by the Stockholm Convention on Persistent Organic Pollutants (POP), an international environmental treaty signed in 2001. PCBs are present in the environment as mixtures of multiple isomers at different degree of chlorination. These compounds are manmade and possess useful industrial properties including extreme longevity under harsh conditions, heat absorbance, and the ability to form an oily liquid at room temperature that is useful for electrical utilities and in other industrial applications. They have been widely used for a wide range of industrial purposes over the decades. Despite a ban in production in 1979 in the US and many other countries, they remain persistent and ubiquitous in environment as contaminants due to their improper disposal. Humans, independent of where they live, are therefore exposed to PCBs, which are routinely found in random surveys of human and animal tissues. The prolonged exposures to PCBs have been associated with the development of different diseases and disorders, and they are classified as endocrine disruptors. Due to its ability to interact with thyroid hormone, metabolism and function, they are thought to be implicated in the global rise of obesity diabetes, and their potential toxicity for neurodevelopment and disorders, an example of gene by environmental interaction (GxE). The current review is primarily intended to summarize the evidence for the association of PCB exposures with increased risks for metabolic dysfunctions and neurobehavioral disorders. In particular, we present evidence of gene expression alterations in PCB-exposed populations to construct the underlying pathways that may lead to those diseases and disorders in course of life. We conclude the review with future perspectives on biomarker-based research to identify susceptible individuals and populations.
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http://dx.doi.org/10.1016/j.envres.2020.110211DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7658018PMC
December 2020

Occupational Hazards and Risks Associated with Phthalates among Slovakian Firefighters.

Int J Environ Res Public Health 2020 04 5;17(7). Epub 2020 Apr 5.

Department of Environmental Medicine, Slovak Medical University, 833 03 Bratislava, Slovakia.

Despite increasing attention to the occupational risk of firefighters, little is known about phthalate exposure. In our study, we detected mono-isobutyl phthalate (MiBP), mono-n-buthyl phthalate (MnBP), mono(2-ethyl-5-hydroxyhexyl) phthalate (5OH-MEHP), mono(2-ethyl-5-carboxypentyl) phthalate (5cx-MECPP), and mono(2-ethyl-5-oxohexyl) phthalate (5oxo-MEHP) in each urine sample. We detected positive association between MnBP, MiBP, mono-2-ethylhexyl phthalate (MEHP), 5OH-MEHP, 5oxo-MEHP, 5cx-MECPP, mono-isononyl phthalate (MiNP), the sum of low (∑LMWP) and high molecular-weight phthalates (∑HMWP). and Tiffeneau-Pinelli index (the ratio of forced expiratory volume in 1/ forced vital capacity; FEV/FVC; = 0.001-0.04) and the percent predicted value (%PV) of FEV/FVC ( = 0.005-0.05) and negative association between MiNP and peak expiratory flow (PEF; r = -0.31; = 0.084). We observed a positive association between phthalate metabolites (MnBP, 5OH-MEHP, 5oxo-MEHP, 5cx-MECPP, 2cx-MMHP, ∑LMWP, and ∑HMWP) and waist-to-hip ratio (WHR; = 0.003-0.09) and body shape index (ABSI; = 0.039-0.09) and a negative association between MnBP, ∑LMWP, and hip circumference ( = 0.005-0.02). We detected association between concentrations of 5OH-MEHP, 5cx-MECPP, 5oxo-MEHP, and MnBP and consumption of food heating in plastic material in microwave ( = 0.02-0.04) and between probands who ate margarines and vegetable fat packed in plastic containers and concentration of MMP ( = 0.03). Results of multivariate regression indicated that exposure to phthalates could be linked with changing body structure, which subsequently affects values of pulmonary functions in firefighters.
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http://dx.doi.org/10.3390/ijerph17072483DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7178246PMC
April 2020

Association of Gestational Weight Gain With Adverse Maternal and Infant Outcomes.

JAMA 2019 05;321(17):1702-1715

Division of Health Data and Digitalization, Norwegian Institute of Public Health, Oslo, Norway.

Importance: Both low and high gestational weight gain have been associated with adverse maternal and infant outcomes, but optimal gestational weight gain remains uncertain and not well defined for all prepregnancy weight ranges.

Objectives: To examine the association of ranges of gestational weight gain with risk of adverse maternal and infant outcomes and estimate optimal gestational weight gain ranges across prepregnancy body mass index categories.

Design, Setting, And Participants: Individual participant-level meta-analysis using data from 196 670 participants within 25 cohort studies from Europe and North America (main study sample). Optimal gestational weight gain ranges were estimated for each prepregnancy body mass index (BMI) category by selecting the range of gestational weight gain that was associated with lower risk for any adverse outcome. Individual participant-level data from 3505 participants within 4 separate hospital-based cohorts were used as a validation sample. Data were collected between 1989 and 2015. The final date of follow-up was December 2015.

Exposures: Gestational weight gain.

Main Outcomes And Measures: The main outcome termed any adverse outcome was defined as the presence of 1 or more of the following outcomes: preeclampsia, gestational hypertension, gestational diabetes, cesarean delivery, preterm birth, and small or large size for gestational age at birth.

Results: Of the 196 670 women (median age, 30.0 years [quartile 1 and 3, 27.0 and 33.0 years] and 40 937 were white) included in the main sample, 7809 (4.0%) were categorized at baseline as underweight (BMI <18.5); 133 788 (68.0%), normal weight (BMI, 18.5-24.9); 38 828 (19.7%), overweight (BMI, 25.0-29.9); 11 992 (6.1%), obesity grade 1 (BMI, 30.0-34.9); 3284 (1.7%), obesity grade 2 (BMI, 35.0-39.9); and 969 (0.5%), obesity grade 3 (BMI, ≥40.0). Overall, any adverse outcome occurred in 37.2% (n = 73 161) of women, ranging from 34.7% (2706 of 7809) among women categorized as underweight to 61.1% (592 of 969) among women categorized as obesity grade 3. Optimal gestational weight gain ranges were 14.0 kg to less than 16.0 kg for women categorized as underweight; 10.0 kg to less than 18.0 kg for normal weight; 2.0 kg to less than 16.0 kg for overweight; 2.0 kg to less than 6.0 kg for obesity grade 1; weight loss or gain of 0 kg to less than 4.0 kg for obesity grade 2; and weight gain of 0 kg to less than 6.0 kg for obesity grade 3. These gestational weight gain ranges were associated with low to moderate discrimination between those with and those without adverse outcomes (range for area under the receiver operating characteristic curve, 0.55-0.76). Results for discriminative performance in the validation sample were similar to the corresponding results in the main study sample (range for area under the receiver operating characteristic curve, 0.51-0.79).

Conclusions And Relevance: In this meta-analysis of pooled individual participant data from 25 cohort studies, the risk for adverse maternal and infant outcomes varied by gestational weight gain and across the range of prepregnancy weights. The estimates of optimal gestational weight gain may inform prenatal counseling; however, the optimal gestational weight gain ranges had limited predictive value for the outcomes assessed.
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http://dx.doi.org/10.1001/jama.2019.3820DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6506886PMC
May 2019

Linking past uses of legacy SVOCs with today's indoor levels and human exposure.

Environ Int 2019 06 13;127:653-663. Epub 2019 Apr 13.

Department of Environmental Medicine, Faculty of Public Health, Slovak Medical University, Limbová 12, 83303 Bratislava, Slovakia.

Semivolatile organic compounds (SVOCs) emitted from consumer products, building materials, and indoor and outdoor activities can be highly persistent in indoor environments. Human exposure to and environmental contamination with polychlorinated biphenyls (PCBs) was previously reported in a region near a former PCB production facility in Slovakia. However, we found that the indoor residential PCB levels did not correlate with the distance from the facility. Rather, indoor levels in this region and those reported in the literature were related to the historic PCB use on a national scale and the inferred presence of primary sources of PCBs in the homes. Other SVOCs had levels linked with either the activities in the home, e.g., polycyclic aromatic hydrocarbons (PAHs) with wood heating; or outdoor activities, e.g., organochlorine pesticides (OCPs) with agricultural land use and building age. We propose a classification framework to prioritize SVOCs for monitoring in indoor environments and to evaluate risks from indoor SVOC exposures. Application of this framework to 88 measured SVOCs identified several PCB congeners (CB-11, -28, -52), hexachlorobenzene (HCB), benzo(a)pyrene, and γ-HCH as priority compounds based on high exposure and toxicity assessed by means of toxicity reference values (TRVs). Application of the framework to many emerging compounds such as novel flame retardants was not possible because of either no or outdated TRVs. Concurrent identification of seven SVOC groups in indoor environments provided information on their comparative levels and distributions, their sources, and informed our assessment of associated risks.
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http://dx.doi.org/10.1016/j.envint.2019.04.001DOI Listing
June 2019

Maternal body mass index, gestational weight gain, and the risk of overweight and obesity across childhood: An individual participant data meta-analysis.

PLoS Med 2019 02 11;16(2):e1002744. Epub 2019 Feb 11.

MRC Lifecourse Epidemiology Unit, University of Southampton, Southampton, United Kingdom.

Background: Maternal obesity and excessive gestational weight gain may have persistent effects on offspring fat development. However, it remains unclear whether these effects differ by severity of obesity, and whether these effects are restricted to the extremes of maternal body mass index (BMI) and gestational weight gain. We aimed to assess the separate and combined associations of maternal BMI and gestational weight gain with the risk of overweight/obesity throughout childhood, and their population impact.

Methods And Findings: We conducted an individual participant data meta-analysis of data from 162,129 mothers and their children from 37 pregnancy and birth cohort studies from Europe, North America, and Australia. We assessed the individual and combined associations of maternal pre-pregnancy BMI and gestational weight gain, both in clinical categories and across their full ranges, with the risks of overweight/obesity in early (2.0-5.0 years), mid (5.0-10.0 years) and late childhood (10.0-18.0 years), using multilevel binary logistic regression models with a random intercept at cohort level adjusted for maternal sociodemographic and lifestyle-related characteristics. We observed that higher maternal pre-pregnancy BMI and gestational weight gain both in clinical categories and across their full ranges were associated with higher risks of childhood overweight/obesity, with the strongest effects in late childhood (odds ratios [ORs] for overweight/obesity in early, mid, and late childhood, respectively: OR 1.66 [95% CI: 1.56, 1.78], OR 1.91 [95% CI: 1.85, 1.98], and OR 2.28 [95% CI: 2.08, 2.50] for maternal overweight; OR 2.43 [95% CI: 2.24, 2.64], OR 3.12 [95% CI: 2.98, 3.27], and OR 4.47 [95% CI: 3.99, 5.23] for maternal obesity; and OR 1.39 [95% CI: 1.30, 1.49], OR 1.55 [95% CI: 1.49, 1.60], and OR 1.72 [95% CI: 1.56, 1.91] for excessive gestational weight gain). The proportions of childhood overweight/obesity prevalence attributable to maternal overweight, maternal obesity, and excessive gestational weight gain ranged from 10.2% to 21.6%. Relative to the effect of maternal BMI, excessive gestational weight gain only slightly increased the risk of childhood overweight/obesity within each clinical BMI category (p-values for interactions of maternal BMI with gestational weight gain: p = 0.038, p < 0.001, and p = 0.637 in early, mid, and late childhood, respectively). Limitations of this study include the self-report of maternal BMI and gestational weight gain for some of the cohorts, and the potential of residual confounding. Also, as this study only included participants from Europe, North America, and Australia, results need to be interpreted with caution with respect to other populations.

Conclusions: In this study, higher maternal pre-pregnancy BMI and gestational weight gain were associated with an increased risk of childhood overweight/obesity, with the strongest effects at later ages. The additional effect of gestational weight gain in women who are overweight or obese before pregnancy is small. Given the large population impact, future intervention trials aiming to reduce the prevalence of childhood overweight and obesity should focus on maternal weight status before pregnancy, in addition to weight gain during pregnancy.
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http://dx.doi.org/10.1371/journal.pmed.1002744DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6370184PMC
February 2019

Environmental ototoxicants, a potential new class of chemical stressors.

Environ Res 2019 04 26;171:378-394. Epub 2019 Jan 26.

Slovak Medical University, Faculty of Public Health, Department of Environmental Medicine, Limbova 12, 83303 Bratislava, Slovakia. Electronic address:

Hearing loss is an injury that can develop over time, and people may not even be aware of it until it becomes a severe disability. Ototoxicants are substances that may damage the inner ear by either affecting the structures in the ear itself or by affecting the nervous system. We have examined the possibility that ototoxicants may present a health hazard in association with environmental exposures, adding to existing knowledge of their proven hazards under medical therapeutic conditions or occupational activities. In addition to the already described human environmental ototoxicants, mainly organochlorines such as polychlorinated biphenyls (PCBs), polychlorinated dibenzo-p-dioxins (PCDDs), dibenzofurans (PCDFs), dichlorodiphenyltrichloroethane (DDT), dichlorodiphenyldichloroethylene (DDE), hexachlorocyclohexane (HCH) and hexachlorobenzene (HCB), we have examined the ubiquitous chemical stressors phthalates, bisphenol A/S/F/, PFCs, flame retardants (FRs) and cadmium for potential ototoxic properties, both as single substances or as chemical mixtures. Our literature review confirmed that these chemicals may disturb thyroid hormones homeostasis, activate aryl hydrocarbon receptor (AhR), and induce oxidative stress, which in turn may initiate a chain of events resulting in impairment of cochlea and hearing loss. With regard to auditory plasticity, diagnostics of a mixture of effects of ototoxicants, potential interactions of chemical and physical agents with effects on hearing, parallel deterioration of hearing due to chemical exposures and ageing, metabolic diseases or obesity, even using specific methods as brainstem auditory evoked potentials (BAEP) or otoacoustic emissions (OAEs) registration, may be difficult, and establishment of concentration-response relationships problematic. This paper suggests the establishment of a class of environmental oxotoxicants next to the established classes of occupational and drug ototoxicants. This will help to properly manage risks associated with human exposure to chemical stressors with ototoxic properties and adequate regulatory measures.
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http://dx.doi.org/10.1016/j.envres.2019.01.042DOI Listing
April 2019

Prenatal and Early Postnatal Exposure to Total Mercury and Methylmercury from Low Maternal Fish Consumption.

Biol Trace Elem Res 2019 Sep 29;191(1):16-26. Epub 2018 Nov 29.

Department of Clinical and Experimental Pharmacotherapy, Faculty of Medicine, Slovak Medical University in Bratislava, Limbova 12, 833 03, Bratislava, Slovak Republic.

The aim of this study was to investigate the influence of low fish consumption on prenatal and early postnatal exposure to mercury species. The samples of umbilical cord blood and maternal milk as well as interviewer-administered questionnaires were collected from 142 Slovak mother-child pairs. The mean total mercury (THg) concentrations in cord blood and milk were 0.949 μg/L and 0.376 μg/kg, respectively. The mean methylmercury (MeHg) concentration in cord blood was 0.504 μg/L. Fish eaters had significantly higher cord blood MeHg concentrations than non-fish eaters (p = 0.030); no difference was found in milk or cord blood THg concentrations. The bivariate analysis showed a positive correlation between cord blood MeHg and consumption of sea fish and shellfish (r = 0.320, p < 0.001); after adjustment for the potential confounders, the association was weakened (β = 0.173, p = 0.059). Nevertheless, the decision tree method showed sea fish and shellfish consumption to be the best predictor of cord blood MeHg. Furthermore, a negative association was found between THg concentrations in maternal milk and freshwater fish consumption (β = - 0.193, p = 0.017), which might indicate a beneficial effect of freshwater fish consumption. The results suggest there is a need for future research to investigate the benefits versus the adverse effects of low maternal fish consumption on child development.
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http://dx.doi.org/10.1007/s12011-018-1585-6DOI Listing
September 2019

Determinants of prenatal exposure to perfluoroalkyl substances in the Slovak birth cohort.

Environ Int 2018 12 9;121(Pt 2):1304-1310. Epub 2018 Nov 9.

Slovak Medical University, Faculty of Public Health, Department of Environmental Medicine, Bratislava, Slovakia. Electronic address:

Background: 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.

Methods: 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.

Results: 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%CI[1.03; 1.53]), PFOA (exp. β = 1.49; 95%CI[1.18; 1.89]), PFNA (exp. β = 1.30; 95%CI[1.05; 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%CI[1.04; 1.55] and exp. β = 1.30; 95%CI[1.06; 1.60], respectively) and higher educational level of mother was associated with higher PFNA levels (exp. β = 1.32; 95%CI[1.04; 1.68]). Higher fish consumption was associated with lower PFNA levels (exp. β = 0.49; 95%CI[0.26; 0.92]).

Conclusions: 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.
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http://dx.doi.org/10.1016/j.envint.2018.10.051DOI Listing
December 2018

Gestational weight gain charts for different body mass index groups for women in Europe, North America, and Oceania.

BMC Med 2018 11 5;16(1):201. Epub 2018 Nov 5.

Departments of Public Health Sciences and Environmental Medicine, University of Rochester School of Medicine and Dentistry, Rochester, NY, USA.

Background: Gestational weight gain differs according to pre-pregnancy body mass index and is related to the risks of adverse maternal and child health outcomes. Gestational weight gain charts for women in different pre-pregnancy body mass index groups enable identification of women and offspring at risk for adverse health outcomes. We aimed to construct gestational weight gain reference charts for underweight, normal weight, overweight, and grades 1, 2 and 3 obese women and to compare these charts with those obtained in women with uncomplicated term pregnancies.

Methods: We used individual participant data from 218,216 pregnant women participating in 33 cohorts from Europe, North America, and Oceania. Of these women, 9065 (4.2%), 148,697 (68.1%), 42,678 (19.6%), 13,084 (6.0%), 3597 (1.6%), and 1095 (0.5%) were underweight, normal weight, overweight, and grades 1, 2, and 3 obese women, respectively. A total of 138, 517 women from 26 cohorts had pregnancies with no hypertensive or diabetic disorders and with term deliveries of appropriate for gestational age at birth infants. Gestational weight gain charts for underweight, normal weight, overweight, and grade 1, 2, and 3 obese women were derived by the Box-Cox t method using the generalized additive model for location, scale, and shape.

Results: We observed that gestational weight gain strongly differed per maternal pre-pregnancy body mass index group. The median (interquartile range) gestational weight gain at 40 weeks was 14.2 kg (11.4-17.4) for underweight women, 14.5 kg (11.5-17.7) for normal weight women, 13.9 kg (10.1-17.9) for overweight women, and 11.2 kg (7.0-15.7), 8.7 kg (4.3-13.4) and 6.3 kg (1.9-11.1) for grades 1, 2, and 3 obese women, respectively. The rate of weight gain was lower in the first half than in the second half of pregnancy. No differences in the patterns of weight gain were observed between cohorts or countries. Similar weight gain patterns were observed in mothers without pregnancy complications.

Conclusions: Gestational weight gain patterns are strongly related to pre-pregnancy body mass index. The derived charts can be used to assess gestational weight gain in etiological research and as a monitoring tool for weight gain during pregnancy in clinical practice.
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http://dx.doi.org/10.1186/s12916-018-1189-1DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6217770PMC
November 2018

The spatial distribution of congener-specific human PCB concentrations in a PCB-polluted region.

Sci Total Environ 2019 Feb 11;651(Pt 2):2292-2303. Epub 2018 Oct 11.

Slovak Medical University, Limbová 12, 83303 Bratislava, Slovakia. Electronic address:

Serum PCB congener concentrations were measured in 602 adults living near a PCB pollution source in eastern Slovakia. We created isoconcentration maps for 21 PCB congeners by geocoding each participant's place of residence and kriging. Concentrations of PCB congeners were inversely associated with the distance of the participants' residence from the source of pollution. Congener-specific risk factors were derived, particularly for PCBs 52 and 153. We observed that the spatial distribution of serum concentrations was influenced by micro-climatic parameters and physicochemical properties of the congeners. PCB congener profiles strongly correlated with that of the PCB commercial product Delor 106, which was manufactured in the region. The isoconcentration maps indicate that the zones with the highest predicted congener concentration have a mean area of approximately 235.75±188.56km and the mean enrichment of concentration of congeners in serum in these zones is about 5.12±1.36. We estimate that depending on congener approximately 23,457±18,762 individuals with PCB concentrations exceeding health-based guidance values live in these zones.
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http://dx.doi.org/10.1016/j.scitotenv.2018.10.123DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6246788PMC
February 2019

Prenatal and postnatal exposure to persistent organic pollutants and attention-deficit and hyperactivity disorder: a pooled analysis of seven European birth cohort studies.

Int J Epidemiol 2018 08;47(4):1082-1097

Department of Environmental Exposure and Epidemiology, Norwegian Institute of Public Health, Oslo, Norway.

Background: Attention-deficit/hyperactivity disorder (ADHD) is increasing worldwide for reasons largely unknown and environmental chemicals with neurotoxic properties, such as persistent organic pollutants (POPs), have been proposed to play a role. We investigated the association between prenatal and postnatal exposure to polychlorinated biphenyl-153 (PCB-153), p-p´-dichlorodiphenyldichloroethylene (p-p'-DDE) and hexachlorobenzene (HCB) and ADHD in childhood.

Methods: We pooled seven European birth cohort studies encompassing 4437 mother-child pairs from the general population with concentrations of PCB-153, p-p´-DDE and HCB measured in cord blood, maternal blood or milk. We then calculated prenatal (birth) and postnatal (3, 6, 12 and 24 months) POP concentrations using a pharmacokinetic model. The operational definition of ADHD varied across cohorts and ranged from doctor diagnosis obtained from patient registries to maternal or teachers reports. We used multilevel (mixed) logistic regression models to estimate the associations between exposure to POPs at birth, 3, 6, 12 and 24 months and ADHD.

Results: The global prevalence of ADHD in our study was 6%. The mean age at assessment of ADHD was 5.8 years (range: 3.8-9.5 years). We found no association between exposure to PCB-153, p-p´-DDE and HCB at any age point between birth and 24 months and ADHD, in the pooled analyses (pooled odds ratios ranging from 1.00 to 1.01). A number of sensitivity analyses gave basically the same results.

Conclusions: In the largest study to date of 4437 children in seven European birth cohorts, we did not observe any association between either pre- or postnatal exposure (up to 24 months) to PCB-153, p-p´-DDE and HCB and the risk of ADHD before the age of 10 years.
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http://dx.doi.org/10.1093/ije/dyy052DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6124627PMC
August 2018

Prenatal exposure to endocrine disrupting chemicals and risk of being born small for gestational age: Pooled analysis of seven European birth cohorts.

Environ Int 2018 06 30;115:267-278. Epub 2018 Mar 30.

Unit Environmental Risk and Health, Flemish Institute for Technological Research (VITO), Mol, Belgium; Department of Biomedical Sciences, University of Antwerp, Antwerp, Belgium; University of Southern Denmark, Institute of Public Health, Department of Environmental Medicine, Odense, Denmark.

Background And Aims: There is evidence that endocrine disrupting chemicals (EDCs) have developmental effects at environmental concentrations. We investigated whether some EDCs are associated with the adverse birth outcome Small for Gestational Age (SGA).

Methods: We used PCB 153, p,p'-DDE, HCB, PFOS and PFOA measured in maternal, cord blood or breast milk samples of 5446 mother-child pairs (subset of 693 for the perfluorinated compounds) from seven European birth cohorts (1997-2012). SGA infants were those with birth weight below the 10th percentile for the norms defined by gestational age, country and infant's sex. We modelled the association between measured or estimated cord serum EDC concentrations and SGA using multiple logistic regression analyses. We explored effect modification by child's sex and maternal smoking during pregnancy.

Results: Among the 5446 newborns, 570 (10.5%) were SGA. An interquartile range (IQR) increase in PCB 153 was associated with a modestly increased risk of SGA (odds ratio (OR) of 1.05 [95% CI: 1.04-1.07]) that was stronger in girls (OR of 1.09 [95% CI: 1.04-1.14]) than in boys (OR of 1.03 [95% CI: 1.03-1.04]) (p-interaction = 0.025). For HCB, we found a modestly increased odds of SGA in girls (OR of 1.04 [95% CI: 1.01-1.07] per IQR increase), and an inverse association in boys (OR of 0.90 [95% CI: 0.85-0.95]) (p-interaction = 0.0003). Assessment of the HCB-sex-smoking interaction suggested that the increased odds of SGA associated with HCB exposure was only in girls of smoking mothers (OR of 1.18 [95% CI: 1.11-1.25]) (p-interaction = 0.055). Higher concentrations of PFOA were associated with greater risk of SGA (OR of 1.64 [95% CI: 0.97-2.76]). Elevated PFOS levels were associated with increased odds of SGA in newborns of mothers who smoked during pregnancy (OR of 1.63 [95% CI: 1.02-2.59]), while an inverse association was found in those of non-smoking mothers (OR of 0.66 [95% CI: 0.61-0.72]) (p-interaction = 0.0004). No significant associations were found for p,p'-DDE.

Conclusions: Prenatal environmental exposure to organochlorine and perfluorinated compounds with endocrine disrupting properties may contribute to the prevalence of SGA. We found indication of effect modification by child's sex and smoking during pregnancy. The direction of the associations differed by chemical and these effect modifiers, suggesting diverse mechanisms of action and biological pathways.
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http://dx.doi.org/10.1016/j.envint.2018.03.017DOI Listing
June 2018

PCB exposure and potential future cancer incidence in Slovak children: an assessment from molecular finger printing by Ingenuity Pathway Analysis (IPA®) derived from experimental and epidemiological investigations.

Environ Sci Pollut Res Int 2018 Jun 15;25(17):16493-16507. Epub 2017 Nov 15.

Molecular Genetics Laboratory, Department of Biology, Howard University, 415 College Street, NW, Room 408, EE Just Hall, Washington, DC, 20059, USA.

The risk of cancer due to PCB exposure in humans is highly debated. In eastern Slovakia, high exposure of the population to organochlorines (especially PCBs) was associated with various disease and disorder pathways, viz., endocrine disruption, metabolic disorder & diabetes, and cancer, thereby disturbing several cellular processes, including protein synthesis, stress response, and apoptosis. We have evaluated a Slovak cohort (45-month children, at lower and higher levels of PCB exposure from the environment) for disease and disorder development to develop early disease cancer biomarkers that could shed new light on possible mechanisms for the genesis of cancers under such chemical exposures, and identify potential avenues for prevention.Microarray studies of global gene expression were conducted from the 45-month-old children on the Affymetrix platform followed by Ingenuity Pathway Analysis (IPA®) to associate the affected genes with their mechanistic pathways. High-throughput qRT-PCR TaqMan low-density array (TLDA) was performed to further validate the selected genes on the whole blood cells of the most highly exposed children from the study cohort (n = 71). TP53, MYC, BCL2, and LRP12 differential gene expressions suggested strong relationships between potential future tumor promotion and PCB exposure in Slovak children. The IPA analysis further detected the most important signaling pathways, including molecular mechanism of cancers, prostate cancer signaling, ovarian cancer signaling, P53 signaling, oncostatin M signaling, and their respective functions (viz., prostate cancer, breast cancer, progression of tumor, growth of tumor, and non-Hodgkin's disease). The results suggest that PCB exposures, even at the early age of these children, may have lifelong consequences for the future development of chronic diseases.
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http://dx.doi.org/10.1007/s11356-017-0149-1DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5953777PMC
June 2018

Legacy and alternative halogenated flame retardants in human milk in Europe: Implications for children's health.

Environ Int 2017 11 24;108:137-145. Epub 2017 Aug 24.

Research Centre for Toxic Compounds in the Environment, Faculty of Science, Masaryk University, Kamenice 753/5, 625 00 Brno, Czech Republic; Institute for Chemical and Bioengineering, ETH Zürich, Vladimir-Prelog-Weg 1, CH-8093 Zürich, Switzerland. Electronic address:

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 lipid weight (lw) in Norway, the Netherlands and Slovakia, respectively. The sum of the concentrations of AFRs ranged from 0.14 to 0.25ngglw in all countries, which was 2 to 15 times less compared to ΣPBDEs. 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.
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http://dx.doi.org/10.1016/j.envint.2017.08.008DOI Listing
November 2017

Partitioning of hexachlorobenzene between human milk and blood lipid.

Environ Pollut 2017 Oct 1;229:994-999. Epub 2017 Aug 1.

Department of Environmental Medicine, Faculty of Public Health, Slovak Medical University, Limbová 12, 833 03 Bratislava, Slovakia. Electronic address:

In epidemiological studies on the toxic effects of prenatal exposure to hexachlorobenzene (HCB), researchers report HCB concentrations, either as wet-weight or per lipid weight basis, in matrices like breast milk, and maternal and cord blood. Conversion of exposures across matrices is needed for comparisons of concentrations and dose effect across cohorts. Using data from a birth cohort study in eastern Slovakia, we derived the maternal blood to cord blood HCB concentration ratio utilizing measured concentrations in 1027 paired maternal and cord blood samples, on a per-lipid basis. In addition to data from the Slovak study, the maternal milk to maternal serum ratio was summarized from 23 published studies on partitioning of HCB between human milk lipid and blood lipid. We identified two distinct groups of milk:blood ratios, those ≤0.45 and those ≥0.85. We assumed that using partition ratios ≤0.45 will underestimate HCB exposure estimates. Taking into account this precautionary measure, we suggest a conversion ratio of 1.21, which is the median of the 16 ratios identified in our literature review. We consider our estimate as conservative and providing appropriate safety in risk analysis.
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http://dx.doi.org/10.1016/j.envpol.2017.07.087DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6044446PMC
October 2017

Thyroid-stimulating hormone levels in newborns and early life exposure to endocrine-disrupting chemicals: analysis of three European mother-child cohorts.

Pediatr Res 2017 Sep 7;82(3):429-437. Epub 2017 Jun 7.

Department of Environment and Health, Vrije Universiteit, Amsterdam, The Netherlands.

BackgroundVarious studies have reported interactions between thyroid hormones and early life chemical exposure. Our objective was to analyze the associations between markers of endocrine-disrupting chemical exposure and thyroid function in newborns, determined through heel prick blood spots.MethodsThree European mother-child cohorts (FLEHSI-Belgium, HUMIS-Norway, and the PCB cohort-Slovakia. Total n=1,784) were pooled for the purpose of this study. Data on thyroid-stimulating hormone (TSH) were obtained from national neonatal screening registries, and samples of cord plasma and/or breast milk were collected to determine exposure to various chemicals. Multiple regression models were composed with exposure and cohort as fixed factors, and adjustments were made for a priori defined covariates.ResultsMedian TSH concentrations were 1, 1.10, and 2.76 mU/l for the Belgian, Norwegian, and Slovak cohorts, respectively. For polychlorinated biphenyl (PCB)-153 and dichlorodiphenyldichloroethylene (p,p'-DDE), children in the third exposure quartile had a 12-15% lower TSH at birth. Results remained unchanged after additional adjustment for birth weight and gestational weight gain. No effect on TSH was observed for the other compounds.ConclusionEarly life exposure to PCB-153 and p,p'-DDE impacts newborn TSH levels. Higher exposure levels were associated with 12-15% lower TSH levels.
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http://dx.doi.org/10.1038/pr.2017.50DOI Listing
September 2017

Exposure of children to phthalates and the impact of consumer practices in Slovakia.

Rev Environ Health 2017 Mar;32(1-2):211-214

Phthalates are environmental pollutants that can enter the human body by ingestion, inhalation and dermal absorption. Food constitutes the most important source of human exposure to these chemicals. The aim of our study was the biological monitoring of exposure to eight phthalate metabolites in children (n=107), 10-12 years of age, living in eastern Slovakia. Additionally, we analysed some associations between anthropometric measures, questionnaire data (i.e. eating and drinking habits, practice of personal care products) and concentrations of phthalate metabolites. Because of the short half-life of phthalates, within 24-48 h, we used 24-h recalls to assess dietary intakes. We used high-performance liquid chromatography and tandem mass spectrometry for the analysis of spot urine samples to determine concentrations of phthalate metabolites mono-ethyl phthalate (MEP), mono-n-butyl phthalate, mono-iso-butyl phthalate, mono-benzyl phthalate (MBzP), mono (2-ethyl-5-hydroxyhexyl) phthalate (5OH-MEHP), mono(2-ethyl-5-oxohexyl) phthalate (5oxo-MEHP), mono-carboxy pentyl and mono (2-ethylhexyl) phthalate (MEHP). We found statistically significant association between consumer practices and concentration of some phthalate metabolites, concretely consumption of milk and dairy products with MBzP and margarine with MEP (p<0.01 in both cases) and margarine with 5oxo-MEHP, hot beverages with 5OH-MEHP, baguettes and semifinished products with MEP (p<0.05 in all cases). Further, we found relationship between use of cosmetic products and phthalate concentrations, nail polish application and MEP and use of body lotion and MEHP (p<0.05 in both cases). We concluded that consumer practices (including eating and drinking habits and personal care) represent the substantial source of phthalate exposure in Slovak children.
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http://dx.doi.org/10.1515/reveh-2016-0028DOI Listing
March 2017

Relative effect potency estimates of dioxin-like activity for dioxins, furans, and dioxin-like PCBs in adults based on cytochrome P450 1A1 and 1B1 gene expression in blood.

Environ Int 2016 Nov 31;96:24-33. Epub 2016 Aug 31.

Slovak Medical University, Limbová 14, 83303 Bratislava, Slovakia. Electronic address:

Background: In the risk assessment of PCDDs, PCDFs, and dioxin-like (DL) PCBs, regulatory authorities support the use of the toxic equivalency factor (TEF)-scheme derived from a heterogeneous data set of the relative effect potency (REPs) estimates.

Objectives: We sought to determine REPs for dioxin-like compounds (DLCs) using expression of cytochrome P450 (CYP) 1A1 and 1B1 mRNA in human peripheral blood mononuclear cells representing two different pathways.

Methods: We used a sex and age adjusted regression-based approach comparing the strength of association between each DLC and the cytochrome P450 (CYP) 1A1 and 1B1 mRNA expression in 320 adults residing in an organochlorine-polluted area of eastern Slovakia.

Results: We calculated REPs based on CYP1A1 expression for 4 PCDDs, 8 PCDFs, and 1 PCB congener, and based on CYP1B1 expression for 5 PCDFs and 11 PCB congeners. REPs from CYP1A1 correlated with REPs previously derived from thyroid volume (ρ=0.85; p<0.001) and serum FT4 (ρ=0.77; p=0.009). The 13 log REPs from CYP1A1 correlated with log WHO-TEFs (r=0.63; p=0.015) and 11 log PCB REPs with PCB consensus toxicity factors (CTFs) for compounds with WHO-TEFs (r=0.80; p=0.003). The complete set of derived 56 log REPs correlated with the log CTFs (r=0.77; p=0.001) and log WHO-TEFs (r=0.81; p<0.001).

Conclusions: REPs calculated from thyroid and cytochrome P450 endpoints realistically reflect human exposure scenarios because they are based on human chronic and low-dose exposures. While the CYP 1A1 seems more suitable for toxicity evaluation of PCDD/Fs, the CYP 1B1 is more apt for PCDFs and PCBs and reflects different pathways.
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http://dx.doi.org/10.1016/j.envint.2016.08.016DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6047354PMC
November 2016

PCB exposure and cochlear function at age 6 years.

Environ Res 2016 Nov 21;151:428-435. Epub 2016 Aug 21.

Slovak Medical University, Faculty of Public Health, Department of Health Protection, Limbová 12, 833 03 Bratislava 37, Slovak Republic. Electronic address:

Epidemiological studies have documented adverse associations between exposure to polychlorinated biphenyls (PCBs) and otological outcomes. Previously, we documented decreased distortion product otoacoustic emission (DPOAE) levels in children exposed to PCBs, up to the age of 45 months, amongst a cohort of children in eastern Slovakia. The objective of the present study is to evaluate cochlear dysfunction at 72 months of age in 214 children from this same cohort and to compare the otoacoustic test sensitivity to that of pure tone audiometry (PTA). The association between DPOAE, PTA, and PCBs was estimated by means of multivariate ANOVA (MANOVA) and linear regression models. ROC curves were computed to estimate the DPOAE-test power in children. The DPOAE level at 72 months was related to PCB-153 serum levels. The DPOAE Input/Output function test at mid-frequency (2kHz) has shown instead nonmonotonic dependence on PCB exposure, for the left ears of children, over the whole growth curve. No significant association was found between PTA hearing levels and PCB-153 concentration. High diagnostic power of the DPOAE-test was found in children, similar to that found by the same authors in adults. In conclusions the DPOAE-PCB correlation obtained at 72 months is similar to that at 45 months suggesting a permanent and stable ototoxic effect of the PCB exposure. The lack of statistical significance of the PCB-PTA correlation suggests that DPOAEs are sensitive biomarkers of cochlear damage.
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http://dx.doi.org/10.1016/j.envres.2016.08.017DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6044450PMC
November 2016

Occupational exposure to phthalates in relation to gender, consumer practices and body composition.

Environ Sci Pollut Res Int 2016 Dec 17;23(23):24125-24134. Epub 2016 Sep 17.

Department of Environmental Medicine, Slovak Medical University, 833 03, Bratislava, Slovakia.

The aim of our work was to find associations between urinary phthalate metabolite concentrations and occupation, consumer practices and body composition. We divided our cohort (n = 129) into occupationally exposed subjects, community service workers (group A; n = 45) and workers from plastic industry (group B; n = 35) and group of general population (control group C, n = 49). To estimate levels of five phthalate metabolites, we used high-performance liquid chromatography and tandem mass spectrometry analysis. We found in plastic industry workers compared to community service workers and subjects of the control group significantly higher urinary concentration mono (2-ethyl-5-hydroxyhexyl) phthalate (MEHHP), mono (2-ethyl-5-oxohexyl) phthalate (MEOHP), mono (2-etylhexyl) phthalate (MEHP), sum di-(2-ethyl-5-oxohexyl) phthalate (DEHP), mono-iso-butyl phthalate (MiBP) and mono-n-butyl phthalate (MnBP). We identified by multivariate analysis of covariance inverse relationship between MEHP and body parameters as waist-to-height ratio, body mass index, waist-to-hip ratio, hip circumference and waist circumference among females, whereas in males, no significant association was found. Results of our study show, despite of variability in terms of occupational exposure to phthalates, that plastic manufactory represents a higher occupational risk in comparison with waste management. The differences in anthropometric parameters between the two occupationally exposed groups and the general population are suggesting a detrimental effect of occupational exposure on body weight homeostasis.
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http://dx.doi.org/10.1007/s11356-016-7394-6DOI Listing
December 2016

DPOAEs in infants developmentally exposed to PCBs show two differently time spaced exposure sensitive windows.

Chemosphere 2016 Oct 26;161:518-526. Epub 2016 Jul 26.

Slovak Medical University, Limbová 14, 83303, Bratislava, Slovakia. Electronic address:

The study aim was to identify the timing of sensitive windows for ototoxicity related to perinatal exposure to PCBs. A total of 351 and 214 children from a birth cohort in eastern Slovakia underwent otoacoustic testing at 45 and 72 months, respectively, and distortion product otoacoustic emissions (DPOAEs) at 11 frequencies were recorded. Cord and child 6-, 16-, 45-, and 72- month blood samples were analyzed for PCB 153 concentration. The PCB 153 concentration-time profiles were approximated with a system model to calculate area under the PCB*time curves (AUCs) for specific time intervals (3 and 6 months for 45 and 72 months data, respectively). DPOAE amplitudes were correlated (Spearman) with cord serum PCB and AUCs, markers of prenatal and postnatal exposure, respectively. Two exposure critical windows were identified in infants, the first related to prenatal and early postnatal and the second to postnatal exposure to PCBs. Our data have shown tonotopicity, sexual dimorphism, and asymmetry in ototoxicity of PCBs.
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http://dx.doi.org/10.1016/j.chemosphere.2016.07.045DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6042651PMC
October 2016

Perinatal exposure to dioxins and dioxin-like compounds and infant growth and body mass index at seven years: A pooled analysis of three European birth cohorts.

Environ Int 2016 Sep 14;94:399-407. Epub 2016 Jun 14.

Division of Epidemiology, Norwegian Institute of Public Health, Oslo, Norway. Electronic address:

Background: Dioxins and dioxin-like compounds are endocrine disrupting chemicals (EDCs). Experimental studies suggest perinatal exposure to EDCs results in later obesity. However, the few epidemiological investigations on dioxins are inconclusive. We investigated perinatal exposure to dioxins and dioxin-like compounds, infant growth and body mass index (BMI) in childhood.

Methods: We pooled data from 3 European birth cohorts (Belgian, Norwegian, Slovak) with exposure assessment in cord blood or breast milk. Two cohorts had dioxin-like toxicity assessed using dioxin-responsive chemical-activated luciferase expression (DR-CALUX) bioassay and one cohort had measured concentrations of dioxins, furans and dioxin-like polychlorinated biphenols with CALUX relative potency values applied. Growth was cohort- and sex-specific change in weight-for-age z-score between birth and 24months (N=367). BMI was calculated at around 7years (median 7.17, interquartile range [IQR] 7.00-7.37years, N=251), and overweight defined according to international standards for children equivalent to adult BMI >25kg/m(2) (Cole and Lobstein, 2012). We fitted multivariate models using generalized estimating equations, and tested effect modification by sex, breastfeeding and cohort. Results per 10pgCALUXTEQ/g lipid increase in exposure.

Results: Dioxin exposure was highest in the Belgian and lowest in the Norwegian cohort; median (IQR) of the pooled sample 13 (12.0) pgCALUXTEQ/g lipid. Perinatal exposure to dioxins and dioxin-like compounds appeared associated with increased growth between 0 and 24months (adjusted estimate for change in z-score: β=0.07, 95% CI: -0.01, 0.14). At 7years, dioxins exposure was associated with a statistically significant increase in BMI in girls (adjusted estimate for BMI units β=0.49, 95% CI: 0.07, 0.91) but not in boys (β=-0.03, 95% CI: -0.55, 0.49) (p-interaction=0.044). Furthermore, girls had a 54% (-6%, 151%) increased risk of overweight at 7years (p-interaction=0.023).

Conclusion: Perinatal exposure to dioxin and dioxin-like compounds was associated with increased early infant growth, and increased BMI in school age girls. Studies in larger sample sizes are required to confirm these sex-specific effects.
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http://dx.doi.org/10.1016/j.envint.2016.04.040DOI Listing
September 2016

Marijuana: Views on Its Medical Use Recorded at the Slovak Social Network.

J Drug Educ 2016 06 9;46(1-2):3-14. Epub 2016 Jun 9.

Constantine the Philosopher University in Nitra, Slovakia.

We describe opinions on medical use of Cannabis sativa L under conditions of Slovakia (n = 717). Personal experience with marijuana was detected in 77.42% (n = 553) in age categories younger than 20 years (n = 96) and in 77.06% (n = 457) of adults. Almost 86% of respondents (n = 618) agreed with legal use of marijuana for medical purposes. Furthermore, respondents' views on legal usage of marijuana for medical purposes could be affected by availability of information (r = .12) and personal experience (r = .23). Negative impact of substance abuse in younger age-groups was recognized as threat (r = .47), but knowledge about harmful effect of marijuana use did not affect personal opinion for decriminalization (r = .38).
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http://dx.doi.org/10.1177/0047237916646442DOI Listing
June 2016

Demographic, Reproductive, and Dietary Determinants of Perfluorooctane Sulfonic (PFOS) and Perfluorooctanoic Acid (PFOA) Concentrations in Human Colostrum.

Environ Sci Technol 2016 07 14;50(13):7152-62. Epub 2016 Jun 14.

Institute of Environmental Studies, VU University , Amsterdam 1081 HV, The Netherlands.

To determine demographic, reproductive, and maternal dietary factors that predict perfluoroalkyl substance (PFAS) concentrations in breast milk, we measured perfluorooctane sulfonic (PFOS) and perfluorooctanoic acid (PFOA) concentrations, using liquid chromatography-mass spectrometry, in 184 colostrum samples collected from women participating in a cohort study in Eastern Slovakia between 2002 and 2004. During their hospital delivery stay, mothers completed a food frequency questionnaire, and demographic and reproductive data were also collected. PFOS and PFOA predictors were identified by optimizing multiple linear regression models using Akaike's information criterion (AIC). The geometric mean concentration in colostrum was 35.3 pg/mL for PFOS and 32.8 pg/mL for PFOA. In multivariable models, parous women had 40% lower PFOS (95% CI: -56 to -17%) and 40% lower PFOA (95% CI: -54 to -23%) concentrations compared with nulliparous women. Moreover, fresh/frozen fish consumption, longer birth intervals, and Slovak ethnicity were associated with higher PFOS and PFOA concentrations in colostrum. These results will help guide the design of future epidemiologic studies examining milk PFAS concentrations in relation to health end points in children.
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http://dx.doi.org/10.1021/acs.est.6b00195DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5256678PMC
July 2016

A Birth Cohort Study of Maternal and Infant Serum PCB-153 and DDE Concentrations and Responses to Infant Tuberculosis Vaccination.

Environ Health Perspect 2016 06 9;124(6):813-21. Epub 2015 Dec 9.

Department of Public Health Sciences, University of Rochester School of Medicine and Dentistry, Rochester, New York, USA.

Background: Reasons for the highly variable and often poor protection conferred by the Mycobacterium bovis bacille Calmette-Guérin (BCG) vaccine are multifaceted and poorly understood.

Objectives: We aimed to determine whether early-life exposure to PCBs (polychlorinated biphenyls) and DDE [1,1-dichloro-2,2-bis(p-chlorophenyl)ethylene] reduces 6-month infant BCG vaccine response.

Methods: Data came from families participating in a prospective birth cohort in eastern Slovakia. At birth, maternal and cord blood were collected for chemical analyses, and infants were immunized with BCG. Blood was collected from infants for chemical analyses and to determine 6-month BCG-specific immunoglobulin (Ig) G and IgA levels. Multivariable linear regression models were fit to examine chemical-BCG associations among approximately 500 mother-infant pairs, with adjustment for confounders.

Results: The median 6-month infant concentration of the prevalent congener PCB-153 was 113 ng/g lipid [interquartile range (IQR): 37-248], and 388 ng/g lipid (IQR: 115-847) for DDE. Higher 6-month infant concentrations of PCB-153 and DDE were strongly associated with lower 6-month BCG-specific antibody levels. For instance, BCG-specific IgG levels were 37% lower for infants with PCB-153 concentrations at the 75th percentile compared to the 25th percentile (95% CI: -42, -32; p < 0.001). Results were similar in magnitude and precision for DDE. There was also evidence of PCB-DDE additivity, where exposure to both compounds reduced anti-BCG levels more than exposure to either compound alone.

Conclusions: The associations observed in this study indicate that environmental exposures may be overlooked contributors to poorer responses to BCG vaccine. The overall association between these exposures and tuberculosis incidence is unknown.

Citation: Jusko TA, De Roos AJ, Lee SY, Thevenet-Morrison K, Schwartz SM, Verner MA, Palkovicova Murinova L, Drobná B, Kočan A, Fabišiková A, Čonka K, Trnovec T, Hertz-Picciotto I, Lawrence BP. 2016. A birth cohort study of maternal and infant serum PCB-153 and DDE concentrations and responses to infant tuberculosis vaccination. Environ Health Perspect 124:813-821; http://dx.doi.org/10.1289/ehp.1510101.
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http://dx.doi.org/10.1289/ehp.1510101DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4892928PMC
June 2016

Simple reaction time in 8-9-year old children environmentally exposed to PCBs.

Neurotoxicology 2015 Dec 19;51:138-44. Epub 2015 Oct 19.

Department of Environmental Medicine, Slovak Medical University, Limbová 12, 83303 Bratislava, Slovakia. Electronic address:

Simple reaction time (SRT) has been studied in children exposed to polychlorinated biphenyls (PCBs), with variable results. In the current work we examined SRT in 146 boys and 161 girls, aged 8.53 ± 0.65 years (mean ± SD), exposed to PCBs in the environment of eastern Slovakia. We divided the children into tertiles with regard to increasing PCB serum concentration. The mean ± SEM serum concentration of the sum of 15 PCB congeners was 191.15 ± 5.39, 419.23 ± 8.47, and 1315.12 ± 92.57 ng/g lipids in children of the first, second, and third tertiles, respectively. We created probability distribution plots for each child from their multiple trials of the SRT testing. We fitted response time distributions from all valid trials with the ex-Gaussian function, a convolution of a normal and an additional exponential function, providing estimates of three independent parameters μ, σ, and τ. μ is the mean of the normal component, σ is the standard deviation of the normal component, and τ is the mean of the exponential component. Group response time distributions were calculated using the Vincent averaging technique. A Q-Q plot comparing probability distribution of the first vs. third tertile indicated that deviation of the quantiles of the latter tertile from those of the former begins at the 40th percentile and does not show a positive acceleration. This was confirmed in comparison of the ex-Gaussian parameters of these two tertiles adjusted for sex, age, Raven IQ of the child, mother's and father's education, behavior at home and school, and BMI: the results showed that the parameters μ and τ significantly (p ≤ 0.05) increased with PCB exposure. Similar increases of the ex-Gaussian parameter τ in children suffering from ADHD have been previously reported and interpreted as intermittent attentional lapses, but were not seen in our cohort. Our study has confirmed that environmental exposure of children to PCBs is associated with prolongation of simple reaction time reflecting impairment of cognitive functions.
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http://dx.doi.org/10.1016/j.neuro.2015.10.005DOI Listing
December 2015

The spatial distribution of human exposure to PCBs around a former production site in Slovakia.

Environ Sci Pollut Res Int 2015 Oct 7;22(19):14405-15. Epub 2015 Aug 7.

Slovak Medical University, Limbová 12, 83303, Bratislava, Slovakia.

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.
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http://dx.doi.org/10.1007/s11356-015-5047-9DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4677688PMC
October 2015

Environmental exposure to organochlorine pesticides and deficits in cochlear status in children.

Environ Sci Pollut Res Int 2015 Oct 21;22(19):14570-8. Epub 2015 May 21.

Department of Environmental Medicine, Slovak Medical University, Limbová 12, 83303, Bratislava, Slovakia.

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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http://dx.doi.org/10.1007/s11356-015-4690-5DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4592791PMC
October 2015

Prenatal and Postnatal Exposure to Persistent Organic Pollutants and Infant Growth: A Pooled Analysis of Seven European Birth Cohorts.

Environ Health Perspect 2015 Jul 6;123(7):730-6. Epub 2015 Mar 6.

Division of Epidemiology, Norwegian Institute of Public Health, Oslo, Norway.

Background: Infant exposure to persistent organic pollutants (POPs) may contribute to obesity. However, many studies so far have been small, focused on transplacental exposure, used an inappropriate measure to assess postnatal exposure through breastfeeding if any, or did not discern between prenatal and postnatal effects.

Objectives: We investigated prenatal and postnatal exposure to POPs and infant growth (a predictor of obesity).

Methods: We pooled data from seven European birth cohorts with biomarker concentrations of polychlorinated biphenyl 153 (PCB-153) (n = 2,487), and p,p'-dichlorodiphenyldichloroethylene (p,p'-DDE) (n = 1,864), estimating prenatal and postnatal POPs exposure using a validated pharmacokinetic model. Growth was change in weight-for-age z-score between birth and 24 months. Per compound, multilevel models were fitted with either POPs total exposure from conception to 24 months or prenatal or postnatal exposure.

Results: We found a significant increase in growth associated with p,p'-DDE, seemingly due to prenatal exposure (per interquartile increase in exposure, adjusted β = 0.12; 95% CI: 0.03, 0.22). Due to heterogeneity across cohorts, this estimate cannot be considered precise, but does indicate that an association with infant growth is present on average. In contrast, a significant decrease in growth was associated with postnatal PCB-153 exposure (β = -0.10; 95% CI: -0.19, -0.01).

Conclusion: To our knowledge, this is the largest study to date of POPs exposure and infant growth, and it contains state-of-the-art exposure modeling. Prenatal p,p'-DDE was associated with increased infant growth, and postnatal PCB-153 with decreased growth at European exposure levels.
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http://dx.doi.org/10.1289/ehp.1308005DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4492262PMC
July 2015
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