Soňa Wimmerová

Acute toxicity of 31 different nanoparticles to zebrafish (Danio rerio) tested in adulthood and in early life stages – comparative study

Abstract At present, nanoparticles are beginning to influence our lives in many ways and understanding the environmental health and safety aspect of nanomaterials has become a crucial issue. The aim of the work was to assess and compare the acute toxicity of 31 different nanomaterials to fish mature individuals Danio rerio with that to fish early life stages on using evaluation of the 48- and 96- hour LC50 values. A further aim was to evaluate teratogenicity of the nanoparticles tested to fish eggs. The nanoparticles tested were: 8 pure metals, 10 metal oxides, 5 other metal compounds and their mixtures, 2 silicon compounds, 3 calcium compounds, and 3 carbon compounds. Using 48-h and 96-h tests of acute toxicity (according to OECD 203), we evaluated mortality data, LC50 values, occurrence of malformations, as well as hatching time. In our study, 6 kinds of nanoparticles - calcium oxide, copper, copper in the form of oxide and CuZnFe4O4, magnesium oxide, and nickel - caused cumulative mortality. Two kinds of nanoparticles - copper and silver - were toxic for fish with LC50 values of approximately 3 mg/L. We did not observe marked differences between the 48-hour and 96-hour acute toxicity LC50 values, yet the possibility to evaluate hatching time in the 96-h acute fish toxicity test seems to be an advantage against that of the 48-hour toxicity.

Prenatal and Postnatal Serum PCB Concentrations and Cochlear Function in Children at 45 Months of Age

Background: 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. Objectives: 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. Methods: 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. Results: 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). Conclusions: In this study, postnatal rather than maternal or cord PCB concentrations were associated with poorer performance on otoacoustic tests at age 45 months. Citation: Jusko TA, Sisto R, Iosif AM, Moleti A, Wimmerová S, Lancz K, Tihányi J, Šovčíková E, Drobná B, Palkovičová L, Jurečková D, Thevenet-Morrison K, Verner MA, Sonneborn D, Hertz-Picciotto I, Trnovec T. 2014. Prenatal and postnatal serum PCB concentrations and cochlear function in children at 45 months of age. Environ Health Perspect 122:1246–1252; http://dx.doi.org/10.1289/ehp.1307473

PCDD/PCDF, dl-PCB and PBDE serum levels of Slovak general population

Blood serum specimens from 81 non-occupationally exposed adults residing in four areas close to municipal and waste incinerators as well as metallurgical industry plant and 44 adult subjects coming from control area of Slovakia were analysed for polychlorinated dibenzo-p-dioxins (PCDDs), polychlorinated dibenzofurans (PCDFs), dioxin-like polychlorinated biphenyls (dl-PCBs) and polybrominated diphenylethers (PBDEs). The concentration of total WHO(98)TEQ PCDD/F/dl-PCBs in whole group of donors from areas where known sources causing dioxin contamination are present was significantly higher than in control group of donors (p<0.001). Correlation between the age of donors and PCDD/F and dl-PCB levels was confirmed (Spearmans r(PCDD/Fs)=0.543, r(dl-PCBs)=0.521, p<0.001). Furthermore, this study presents first results concerning the PBDE congeners in human serum of Slovak general population. The total concentration (congeners 28, 47, 99, 100, 153, 154, 183) in control group was approximately 1.5-times higher in comparison to that of residents coming from areas with supposed environmental pollution. The most abundant congeners in all samples were BDE-47 and BDE-153 with median values of 0.24 ng g(-1) lipid and 0.23ngg(-1) lipid, respectively. The positive association between PBDE values and age of donors was not found.

Half-lives of serum PCB congener concentrations in environmentally exposed early adolescents

The aim was to determine half-life of six most abundant PCB congeners in the body of early adolescents. In 304 environmentally exposed children, PCB serum concentration was determined at the age of 8 and 12years. Half-life was determined for each child assuming exponential decrease or for the whole cohort using multiple regression. Results obtained by both approaches were in agreement. PCB reuptakes corrupting half-life estimates for each child and each congener were evaluated. If one of the serum PCB concentration values fell below the level of detection (LOD) the pair was excluded and if PCB half-life value exceeded the arbitrary value of 30years. The following median half-lives in years 4.46, 10.59, 9.7, 4.7, 9.1 and 9.8 were obtained for PCB congeners 118, 138(+163), 153, 156(+171), 170 and 180, respectively. The elimination half-life values were not systematically related to PCB serum concentration at any examination age. Between half-life values, percentage of children with significant reuptakes and PCB congener abundance in serum were found significant associations.

Ratio of cord to maternal serum PCB concentrations in relation to their congener-specific physicochemical properties

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, R(2)=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.

A normative study of otoacoustic emissions, ear asymmetry, and gender effect in healthy schoolchildren in Slovakia

OBJECTIVE The aim of this normative study was to examine cochlear status and possible ear asymmetry and gender effect in transient evoked and distortion product otoacoustic emissions in a group of healthy 12-year-old children in Slovakia. METHODS Two hundred and twenty-nine 12-year-old children from Slovakia with normal hearing were included in this study. Adolescents with acute infection, abnormal otoscopic findings and abnormal tympanometry were excluded. Pure tone audiometry was performed in standard conditions in a sound proof room. Recordings of transient evoked (TE) and distortion product otoacoustic emissions (DPOAEs) were performed using an ILO 292 USB Echoport. Parameters of hearing thresholds and OAEs were compared using correlation analysis and Wilcoxon test. RESULTS We found highly statistically significant associations between the hearing thresholds for the left and right ears. When comparing pure tone audiometry with OAEs no significant correlation was found. In TEOAE a significant gender effect and side effect in TEOAE SNR were found. On the other hand there was no side effect in TEOAE response level. In DPOAE neither gender nor side effects were determined. CONCLUSIONS This is the first comprehensive information on cochlear status among Slovak adolescents. The TEOAEs were significantly higher in girls than boys, but the ear asymmetry in TEOAE was not significant. For DPOAE responses ear asymmetry and gender did not play a role. The data obtained are a basis for population hearing screening, especially for hearing screening programs in infants and children in Slovakia. Moreover data from particular age group represent a link between data from infants and adults.

Assessment of exposure to PCB 153 from breast feeding and normal food intake in individual children using a system approach model.

Investigators have typically relied on a single or few discrete time points as measures of polychlorinated biphenyl (PCB) body burden, however health effects are more likely to be the result of integrative exposure in time, optionally expressed as an area under the time curve (AUC) of PCB serum concentration. Using data from a subgroup of 93 infants from a birth cohort in eastern Slovakia-a region highly polluted by PCBs-we fit a system type model, customized to our longitudinal measures of serum PCB concentrations in cord, 6, 16, and 45 month blood specimens. The most abundant congener, PCB 153, was chosen for modeling purposes. In addition to currently used methods of exposure assessment, our approach estimates a concentration time profile for each subject, taking into account mean residence time of PCB 153 molecules in the body, duration of breast feeding, hypothetical PCB 153 concentration in steady-state without breast feeding and alternately without normal food intake. Hypothetical PCB 153 concentration in steady-state without normal food intake correlates with AUC (r=0.84, p<0.001) as well as with duration of breast feeding (r=0.64, p<0.001). It makes possible to determine each subjects exposure profile expressed as AUC of PCBs serum concentration with a minimum model parameters. PCB body burden in most infants was strongly associated with duration of breast feeding in most, but not all children, was apparent from model output.

Duration of breastfeeding and serum PCB 153 concentrations in children

Polychlorinated biphenyls (PCBs) are toxic, persistent, and bioaccumulative chemicals which, because of their lipophilic properties, are abundant in human breast milk. Breastfed infants are therefore at risk of being exposed to considerable amounts of PCBs. The commonly used exposure estimations, based solely on breast milk PCB levels and duration of breastfeeding, may lead to exposure misclassification. To improve assessments of exposure to PCBs, we determined PCB 153 serum concentration, as a model substance for PCBs, at the critical time of weaning for each child in 305 breastfed infants from 5 single time point concentration measurements spread over 7 years and data on duration of breastfeeding, using an earlier developed model of the system type. We approximated the dependence of PCB 153 serum concentration, Ctbf, adjusted to cord serum concentration, C0, on nursing period, by a polynomial function Ctbf/C0=0.596+0.278t-0.0047t(2) which reliably predicts exposure to PCB 153 of breastfed infants, important for assessment of dose-outcome relationships. Adjustment of current serum concentrations to cord serum concentration improved validity of exposure assessment.

Polychlorinated biphenyls and selected organochlorine pesticides in serum of Slovak population from industrial and non-industrial areas.

The concentrations of indicator polychlorinated biphenyls (PCBs No. 28, 52, 101, 138, 153 and 180) and organochlorine pesticides (HCB, p,p′-DDE and p,p′-DDT) in 121 blood serum specimens collected from non-occupationally exposed adults living in contaminated and comparison areas were determined using high-resolution gas chromatography/electron capture detection (HRGC/ECD). The sum of the serum concentrations of the three most abundant PCB congeners (No. 138, 153 and 180) found in participants (N = 81) living in industrial areas near incinerators, metallurgical and chemical plants (Krompachy, Kosice, Nemecka and Sala) was significantly higher (p < 0.001) than in participants living in villages and towns without known sources causing persistent organic pollutant (POP) contamination (N = 40). Similarly, significant differences were observed for p,p′-DDE (p < 0.0001) and p,p′-DDT (p < 0.002). However, a Mann-Whitney U test between groups showed that the difference for HCB was not statistically significant (p = 0.089). Age was positively correlated with the sum of PCBs (No. 138, 153 and 180), HCB and the sum of p,p′-DDE and p,p′-DDT (p < 0.01 for all).

Inflammatory and Haematotoxic Potential of Indoor Stachybotrys chartarum (Ehrenb.) Hughes Metabolites

Inflammatory and Haematotoxic Potential of Indoor Stachybotrys chartarum (Ehrenb.) Hughes Metabolites Mould Stachybotrys chartarum (Ehrenb.) Hughes is known to pose a health risk in indoor environments. Most of its strains can produce several intra- and extracellular trichothecene mycotoxins. Complex secondary metabolites of stachybotrys isolates from mouldy dwellings/public buildings in Slovakia were intratracheally instilled in Wistar male rats (4 μg in 0.2 mL of 0.2 % dimethylsulphoxide; diacetoxyscirpenol as the positive control). After three days, haematological parameters were measured in peripheral blood and inflammatory response biomarkers in bronchoalveolar lavage fluid (BALF), and the results were statistically analysed. Exometabolites proved to suppress red blood cell (RBC), decreasing the total RBC count, haemoglobin, and haematocrit. The exposed rats showed significantly higher total BALF cell count, indicating inflammation, lower alveolar macrophage counts, and increased granulocyte count related to the BALF cells. Due to haematotoxic and inflammation-inducing properties, metabolites of S. chartarum can cause damage to the airways and haematological disorders in occupants of mouldy buildings. Upalni i hematotoksični potencijal metabolita plijesni Stachybotrys chartarum (Ehrenb.) Hughes u zatvorenim prostorijama Plijesan Stachybotrys chartarum (Ehrenb.) Hughes poznata je kao rizični mikroorganizam u zatvorenim prostorijama. Većina njezinih sojeva može proizvesti nekoliko unutarstaničnih i izvanstaničnih trikotecenskih mikotoksina. Muškim Wistar štakorima instilirani su intratrahealno kompleksni sekundarni metaboliti stahibotrisa izolirani iz stambenih i javnih zgrada u Slovačkoj zahvaćenima plijesni (4 μg na 0,2 mL 0,2 %-tnog dimetilsulfoksida; dok se diacetoksiscirpenol rabio kao pozitivna kontrola). Tri dana kasnije izmjereni su hematološki parametri u perifernoj krvi te biopokazatelji upalnoga odgovora u bronhoalveolarnome ispirku te su rezultati obrađeni statistički. Pokazalo se da egzometaboliti suprimiraju eritrocite, smanjujući njihov ukupni broj, hemoglobin i hematokrit. Izloženi štakori imali su značajno veći broj stanica u bronhoalveolarnome ispirku, što upućuje na upalu, dok im je broj alveolarnih makrofaga bio manji, a broj granulocita povezanih sa stanicama u ispirku veći. Zbog svojih hematotoksičnih i upalnih svojstava S. chartarum može dovesti do oštećenja dišnih putova i poremećaja u krvotvornome sustavu osoba koje žive i/ili rade u zgradama zahvaćenima tom plijesni.