BACKGROUND: Exposure to benzophenone-1 (BP-1) and benzophenone-3 (BP-3), widely used as UV filters in personal care products, has been associated with adverse health effects. However, epidemiological evidence is limited and inconclusive, particularly in vulnerable populations such as teenagers. OBJECTIVE: To examine the relation between BP-1 and BP-3 concentrations and obesity, cardiometabolic biomarkers, and asthma/allergy outcomes in European teenagers, including possible sex-specific associations. METHODS: A multi-country cross-sectional study was conducted using pooled data from six aligned studies from the Human Biomonitoring for Europe Initiative (HBM4EU). Sociodemographic data, cardiometabolic biomarkers, and asthma/allergy outcomes were collected through questionnaires. Anthropometric data and BMI z-scores were calculated (n = 1339). Plasma/serum cardiometabolic biomarkers and asthma/allergy outcomes were available for a subsample (n = 173-594). Urinary BP-1 and BP-3 concentrations were adjusted for creatinine dilution using the traditional standardization (trad.) and the covariate-adjusted creatinine standardization (CAS) method. Generalized additive models, linear, logistic, and multinomial mixed models were applied, and sex-interaction terms were tested. RESULTS: Each natural log-unit increase in urinary BP-3 (CAS) concentrations was associated with higher odds of obesity in the whole population (OR: 1.20; 95%CI: 1.04-1.38). Sex-specific associations were also found with BP-1 (CAS) and BP-3 (CAS) concentrations, which were associated with higher odds of obesity in male teenagers (OR: 1.25; 95% CI: 1.01-1.55; OR: 1.34; 95%CI: 1.09-1.65, respectively). Linear mixed models showed consistent findings toward higher BMI z-scores. A negative association was found between BP-1 (CAS) concentration and serum adiponectin levels in females (% change per loge-unit increase: -3.73, 95%CI: -7.32, -0.10). BP-3 (CAS) concentrations were also associated with higher odds of non-food allergies in males (OR: 1.27; 95%CI: 1.00-1.63). Traditional creatinine adjustment showed similar or slightly attenuated estimates compared to the CAS method. CONCLUSIONS: BP-1 and BP-3 exposure was cross-sectionally associated with higher odds of obesity in European male teenagers, highlighting the need to update regulations and keep exposure levels as low as practically achievable. Longitudinal studies are needed to confirm these findings.

• Klíčová slova
• Allergy, Benzophenone, Endocrine disruption, HBM4EU, Obesity, PARC, UV filter,
• MeSH
• alergie * epidemiologie   MeSH
• benzofenony * toxicita   moč   škodlivé účinky   MeSH
• biologické markery krev   MeSH
• biologický monitoring MeSH
• bronchiální astma * epidemiologie   chemicky indukované   MeSH
• lidé MeSH
• mladiství MeSH
• obezita * epidemiologie   chemicky indukované   MeSH
• přípravky chránící proti slunci * škodlivé účinky   MeSH
• průřezové studie MeSH
• vystavení vlivu životního prostředí * MeSH
• Check Tag
• lidé MeSH
• mladiství MeSH
• mužské pohlaví MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• Geografické názvy
• Evropa epidemiologie   MeSH
• Názvy látek
• benzofenony * MeSH
• biologické markery MeSH
• přípravky chránící proti slunci * MeSH

Workplace monitoring of hazardous medicinal products (HMPs) using surface wipe sampling is becoming common practice in many European hospitals and pharmacies. However, no independent quality control is available to validate wiping procedures and analytical methods. This study aimed to conduct a Europe-wide interlaboratory comparison (ILC) program to independently and blindly assess laboratory performance and variability in HMP detection. Four European laboratories participated in the study. Six HMPs-cyclophosphamide, etoposide, gemcitabine, ifosfamide, methotrexate, and paclitaxel-were prepared at four concentrations (5000, 2000, 200, and 20 ng/mL) and applied to a 400-cm2 stainless-steel surface, then wiped by the coordinating body according to each laboratory's protocol. Wipe samples were distributed to individual laboratories, where blind analyses were conducted. Target criteria for accuracy and recovery were set at 70%-130% and 50%-130%, respectively. Of the 80 samples, 69 (86%) met accuracy targets, and 70 (88%) met recovery targets. Accuracy was often overestimated for the lowest concentrations of cyclophosphamide, etoposide, methotrexate, and paclitaxel by Laboratory A. Laboratory D showed low accuracy for paclitaxel at three lower concentrations. Among the 10 samples that did not meet recovery targets, all were below 50% and involved etoposide and paclitaxel. This ILC program demonstrates a viable method for evaluating laboratory performance in HMP detection, offering an external validation mechanism for surface wipe sampling methods. A future goal is to establish a global ILC program with a designated coordinating body for managing it effectively.

• Klíčová slova
• analytical method, antineoplastic drugs, quality control, surface contamination, workplace monitoring,
• Publikační typ
• časopisecké články MeSH

The ever-increasing use of chemicals and the rising incidence of adverse reproductive effects in the modern environment have become an emerging concern. Several studies have shown that environmental contaminants, such as organophosphate flame retardants (OPFRs), negatively impact reproductive health. To evaluate the potential endocrine-related adverse reproductive effects of widely used and priority-listed compound 2-Ethylhexyl diphenyl phosphate (EHDPP), we characterized its effects on adrenal steroidogenesis in human adrenocortical (H295R) cells. The cells were exposed to EHDPP (1 and 5 μM) for 48 h, and the production of hormones, including progesterone, androstenedione, testosterone, estradiol, cortisol, and aldosterone, was measured. In addition, LC-MS/MS-based lipidomics analysis was done to quantify intracellular lipid profiles, and transcriptional assays were performed to examine the expression of genes related to corticosteroidogenesis, lipid metabolism, and mitochondrial dynamics. Our findings indicate that EHDPP disrupts hormone regulation in vitro, as evidenced by increased estradiol, cortisol, and aldosterone secretion. The expression of key corticosteroidogenic genes (CYP11B2, CYP21A1, 3β-HSD2, and 17β-HSD1) was upregulated significantly upon EHDPP exposure. Intracellular lipidomics revealed EHDPP-mediated disruption, including reduced total cholesterol ester, sphingolipids, and increased phospholipids, triglyceride species, and saturated-monounsaturated lipids subspecies. These alterations were accompanied by decreased ACAT2 and SCD1 gene expression. Moreover, a shift in mitochondrial dynamics was indicated by increased MF1 expression and decreased FIS1 expression. These data suggest that EHDPP disrupts adrenal steroidogenesis and lipid homeostasis, emphasizing its potential endocrine-disrupting effects.

• MeSH
• lidé MeSH
• lipidomika MeSH
• metabolismus lipidů * účinky léků   MeSH
• nadledviny * účinky léků   metabolismus   cytologie   MeSH
• organofosfáty * farmakologie   MeSH
• steroidy * biosyntéza   MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• časopisecké články MeSH
• Názvy látek
• organofosfáty * MeSH
• steroidy * MeSH

Emerging environmental contaminants, organophosphate flame retardants (OPFRs), pose significant threats to ecosystems and human health. Despite numerous studies reporting the toxic effects of OPFRs, research on their epigenetic alterations remains limited. In this study, we investigated the effects of exposure to 2-ethylhexyl diphenyl phosphate (EHDPP), tricresyl phosphate (TMPP), and triphenyl phosphate (TPHP) on DNA methylation patterns during zebrafish embryonic development. We assessed general toxicity and morphological changes, measured global DNA methylation and hydroxymethylation levels, and evaluated DNA methyltransferase (DNMT) enzyme activity, as well as mRNA expression of DNMTs and ten-eleven translocation (TET) methylcytosine dioxygenase genes. Additionally, we analyzed genome-wide methylation patterns in zebrafish larvae using reduced-representation bisulfite sequencing. Our morphological assessment revealed no general toxicity, but a statistically significant yet subtle decrease in body length following exposure to TMPP and EHDPP, along with a reduction in head height after TPHP exposure, was observed. Eye diameter and head width were unaffected by any of the OPFRs. There were no significant changes in global DNA methylation levels in any exposure group, and TMPP showed no clear effect on DNMT expression. However, EHDPP significantly decreased only DNMT1 expression, while TPHP exposure reduced the expression of several DNMT orthologues and TETs in zebrafish larvae, leading to genome-wide aberrant DNA methylation. Differential methylation occurred primarily in introns (43%) and intergenic regions (37%), with 9% and 10% occurring in exons and promoter regions, respectively. Pathway enrichment analysis of differentially methylated region-associated genes indicated that TPHP exposure enhanced several biological and molecular functions corresponding to metabolism and neurological development. KEGG enrichment analysis further revealed TPHP-mediated potential effects on several signaling pathways including TGFβ, cytokine, and insulin signaling. This study identifies specific changes in DNA methylation in zebrafish larvae after TPHP exposure and brings novel insights into the epigenetic mode of action of TPHP.

• MeSH
• dánio pruhované * genetika   růst a vývoj   metabolismus   MeSH
• larva * účinky léků   genetika   metabolismus   růst a vývoj   MeSH
• metylace DNA * účinky léků   MeSH
• organofosfáty * toxicita   MeSH
• retardanty hoření toxicita   MeSH
• zvířata MeSH
• Check Tag
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH
• Názvy látek
• organofosfáty * MeSH
• retardanty hoření MeSH
• triphenyl phosphate MeSH Prohlížeč

Perfluorooctanoic acid (PFOA), a member of per- and polyfluoroalkyl substances (PFASs), has been widely used in manufacturing for decades. Currently, PFOA is strictly regulated, but due to its high stability and persistence, it is detected in both environmental as well as in human matrices. To elucidate mechanisms of PFOA toxicity in humans, we determined the genome-wide transcriptomic changes of peripheral blood mononuclear cells (PBMC) responding to PFOA exposure in a sex-stratified analysis. This work employed samples from 145 female and 143 male participants of the CELSPAC: YA study to characterize PFOA-associated transcripts in a broader context using computational analysis. PFOA-associated gene expression differed significantly between men and women, as only 2 % of mapped genes were expressed in both sexes. Disease-specific enrichment analysis revealed cancer and immune-related disease terms as those most enriched in male and female populations. Patterns of enriched terms within the gene set enrichment analysis indicated three main targets of PFOA toxicity: i) lipid metabolism for women; ii) cell cycle regulation for men; and iii) immune system response for both sexes. In summary, our genome-wide transcriptomics analysis described sex-specific differences in PFOA-associated gene expression and provided evidence about biological pathways underlying PFOA toxicity in humans.

• Klíčová slova
• Enrichment analysis, Perfluorooctanoic acid, Peripheral blood mononuclear cells, Sex differences, Transcriptome,
• MeSH
• dospělí MeSH
• exprese genu účinky léků   MeSH
• fluorokarbony * toxicita   MeSH
• kapryláty * toxicita   MeSH
• látky znečišťující životní prostředí toxicita   MeSH
• leukocyty mononukleární účinky léků   metabolismus   MeSH
• lidé MeSH
• mladý dospělý MeSH
• transkriptom účinky léků   MeSH
• vystavení vlivu životního prostředí MeSH
• Check Tag
• dospělí MeSH
• lidé MeSH
• mladý dospělý MeSH
• mužské pohlaví MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• Geografické názvy
• Česká republika MeSH
• Názvy látek
• fluorokarbony * MeSH
• kapryláty * MeSH
• látky znečišťující životní prostředí MeSH
• perfluorooctanoic acid MeSH Prohlížeč

Bisphenol A alternatives are manufactured as potentially less harmful substitutes of bisphenol A (BPA) that offer similar functionality. These alternatives are already in the market, entering the environment and thus raising ecological concerns. However, it can be expected that levels of BPA alternatives will dominate in the future, they are limited information on their environmental safety. The EU PARC project highlights BPA alternatives as priority chemicals and consolidates information on BPA alternatives, with a focus on environmental relevance and on the identification of the research gaps. The review highlighted aspects and future perspectives. In brief, an extension of environmental monitoring is crucial, extending it to cover BPA alternatives to track their levels and facilitate the timely implementation of mitigation measures. The biological activity has been studied for BPA alternatives, but in a non-systematic way and prioritized a limited number of chemicals. For several BPA alternatives, the data has already provided substantial evidence regarding their potential harm to the environment. We stress the importance of conducting more comprehensive assessments that go beyond the traditional reproductive studies and focus on overlooked relevant endpoints. Future research should also consider mixture effects, realistic environmental concentrations, and the long-term consequences on biota and ecosystems.

• Klíčová slova
• BPA alternatives, Biological activity, In silico, Invertebrates, Vertebrates,
• MeSH
• benzhydrylové sloučeniny * toxicita   MeSH
• endokrinní disruptory toxicita   MeSH
• fenoly * toxicita   MeSH
• látky znečišťující životní prostředí * toxicita   MeSH
• lidé MeSH
• monitorování životního prostředí * metody   MeSH
• zvířata MeSH
• Check Tag
• lidé MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH
• přehledy MeSH
• Názvy látek
• benzhydrylové sloučeniny * MeSH
• bisphenol A MeSH Prohlížeč
• endokrinní disruptory MeSH
• fenoly * MeSH
• látky znečišťující životní prostředí * MeSH

While the immunomodulation effects of per- and polyfluoroalkyl substances (PFASs) are described on the level of clinical signs in epidemiological studies (e.g., suppressed antibody response after vaccination), the underlying mechanism has still not been fully elucidated. To reveal mechanisms of PFAS exposure on immunity, we investigated the genome-wide transcriptomic changes of peripheral blood mononuclear cells (PBMCs) responding to PFAS exposure (specifically, exposure to PFPA, PFOA, PFNA, PFDA, PFUnDA, PFHxS, and PFOS). Blood samples and the chemical load in the blood were analyzed under the cross-sectional CELSPAC: Young Adults study. The overall aim of the study was to identify sensitive gene sets and cellular pathways conserved for multiple PFAS chemicals. Transcriptome networks related to adaptive immunity were perturbed by multiple PFAS exposure (i.e., blood levels of at least four PFASs). Specifically, processes tightly connected with late B cell development, such as B cell receptor signaling, germinal center reactions, and plasma cell development, were shown to be affected. Our comprehensive transcriptome analysis identified the disruption of B cell development, specifically the impact on the maturation of antibody-secreting cells, as a potential mechanism underlying PFAS immunotoxicity.

• Klíčová slova
• B cell, Perfluoroalkyl substances, adult cohort, gene expression, immunotoxicity, peripheral blood mononuclear cells, plasma cell, transcriptomics,
• MeSH
• fluorokarbony * toxicita   MeSH
• kyseliny alkansulfonové * MeSH
• látky znečišťující životní prostředí * MeSH
• leukocyty mononukleární MeSH
• lidé MeSH
• mladý dospělý MeSH
• průřezové studie MeSH
• transkriptom MeSH
• Check Tag
• lidé MeSH
• mladý dospělý MeSH
• Publikační typ
• časopisecké články MeSH
• Geografické názvy
• Česká republika MeSH
• Názvy látek
• fluorokarbony * MeSH
• kyseliny alkansulfonové * MeSH
• látky znečišťující životní prostředí * MeSH

In recent decades, male infertility has been on the rise, largely attributed to exposure to chemicals with endocrine-disrupting properties. The adverse effects of disrupting androgen actions on the development and reproductive health of children and adolescents have been extensively studied. Flame retardants (FRs), used in consumer products to delay flammability, have been identified as antagonists of the androgen receptor (AR), potentially leading to adverse outcomes in male reproductive health later in life. This study examined the interaction of eight novel FRs with the AR, employing an in vitro AR-dependent luciferase reporter gene assay utilizing MDA-kb2 cells. The investigation revealed the anti-androgenic activity of tris(2,3-dibromopropyl) isocyanurate (TDBP-TAZTO), a frequently detected FR in the environment. Furthermore, TDBP-TAZTO contributed to anti-androgenic activity when combined with six other anti-androgenic FRs. The mixture effects were predicted by three commonly employed models: concentration addition (CA), generalized CA, and independent action, with the CA model showcasing the highest accuracy. This suggests that all FRs act through a similar mechanism, as further confirmed by in silico molecular docking, indicating limited synergy or antagonism. Importantly, in the mixtures, each FR contributed to the induction of anti-androgenic effects at concentrations below their individual effective concentrations in single exposures. This raises concern for public health, especially considering the co-detection of these FRs and their potential co-occurrence with other anti-androgenic chemicals like bisphenols. Therefore, our findings, along with previous research, strongly support the incorporation of combined effects of mixtures in risk assessment to efficiently safeguard population health.

• Klíčová slova
• Additive effect, Antiandrogen, Chemical mixture, Endocrine disruptor, Fertility, Flame retardant,
• MeSH
• androgeny farmakologie   MeSH
• antagonisté androgenů * toxicita   MeSH
• dítě MeSH
• lidé MeSH
• mladiství MeSH
• retardanty hoření * toxicita   MeSH
• simulace molekulového dockingu MeSH
• Check Tag
• dítě MeSH
• lidé MeSH
• mladiství MeSH
• mužské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• Názvy látek
• androgeny MeSH
• antagonisté androgenů * MeSH
• retardanty hoření * MeSH

BACKGROUND: Per- and polyfluoroalkyl substances (PFASs) are emerging environmental contaminants with multiple hazardous properties including immunomodulation potency. Human exposure to PFASs has been associated with various immune-mediated diseases and outcomes. This study aimed to investigate the association between PFAS exposure and immune-mediated diseases such as allergies, eczemas, and autoimmune diseases in a population of adults in the Czech Republic. METHODS: This study included 309 adults from the Central European Longitudinal Study of Parents and Children: Young Adults (CELSPAC: YA). 12 PFASs were measured in participants' serum by HPLC-MS/MS, 3 PFASs were removed from the subsequent analyses due to low detection frequency. The associations of 9 PFASs with 9 immune-mediated diseases were assessed by logistic regression. Furthermore, Bayesian kernel machine regression (BKMR) was used to estimate the effect of the PFAS mixture on immune-mediated diseases. All analyses were adjusted for sex, age, BMI, smoking, education, and family history of immune-mediated diseases. In cases of a statistically significant interaction of PFASs and sex, stratified analyses were performed for men and women. RESULTS: Perfluorooctanoate (PFOA) and perfluorooctane sulfonate (PFOS) were negatively associated with both atopic eczema (OR per IQR increase 0.58 (95% CI 0.37-0.90) for PFOA and 0.56 (0.32-0.95) for PFOS) and contact dermatitis (0.37 (0.16-0.85) for PFOA and 0.33 (0.11-0.94) for PFOS). Perfluoroundecanoate (PFUnDA) was negatively associated with pollen, dust, and mite allergy (0.62 (0.43-0.89)). BKMR modelling showed a negative tendency in the overall effect of PFAS mixture on immune-health outcomes. Based on the stratified analysis, sex was suggested to be an effect modifier in the association of PFOS and atopic eczema. CONCLUSION: Our results contribute to the body of literature that observes the immunosuppressive effect of PFAS exposure during eczemas and allergies, both for PFASs individually and as a mixture.

• Klíčová slova
• Adult cohort, Allergy, Bayesian kernel machine regression, Eczema, Immune system, Perfluoroalkyl substances,
• MeSH
• alergie * MeSH
• atopická dermatitida * chemicky indukované   epidemiologie   MeSH
• Bayesova věta MeSH
• dítě MeSH
• ekzém * MeSH
• fluorokarbony * toxicita   MeSH
• kyseliny alkansulfonové * toxicita   MeSH
• látky znečišťující životní prostředí * toxicita   MeSH
• lidé MeSH
• longitudinální studie MeSH
• mladý dospělý MeSH
• prevalence MeSH
• tandemová hmotnostní spektrometrie MeSH
• Check Tag
• dítě MeSH
• lidé MeSH
• mladý dospělý MeSH
• mužské pohlaví MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• Geografické názvy
• Česká republika epidemiologie   MeSH
• Názvy látek
• fluorokarbony * MeSH
• kyseliny alkansulfonové * MeSH
• látky znečišťující životní prostředí * MeSH
• perfluorooctane sulfonic acid MeSH Prohlížeč
• perfluorooctanoic acid MeSH Prohlížeč

Oxidative stress is an important toxicity and genotoxicity mechanism of many chronic adverse health outcomes. This study developed a sensitive extraction method for urine matrix (based on lyophilization, without the need for pre-cleaning by solid phase extraction), coupled to LC-MS/MS analysis of the biomarker 8-hydroxy-2'-deoxyguanosine (8-OHdG). The methodology was validated in urine samples from a cohort of Spanish pregnant women collected during the first, second and third trimester of pregnancy, and urine samples collected within 24 h after delivery (n = 85). A detection and quantification limit of 0.01 and 0.05 μg/L, respectively, were established. The median 8-OHdG concentration was 2.18 μg/L (range 0.33-7.79); and the corresponding creatinine-adjusted concentrations ranged from 1.04 to 13.12 with median of 4.48 μg 8-OHdG/g creatinine. The concentrations of non-adjusted 8-OHdG significantly decreased (p < 0.05) in the 3rd trimester and post-delivery urine samples when compared to the 1st trimester levels. 8-OHdG concentrations were further studied in placenta samples matching the same urine samples (n = 26), with a median value of 1.3 ng 8-OHdG/g of tissue. Placental 8-OHdG concentrations were correlated with urinary levels of non-adjusted 8-OHdG in the 3rd trimester. Considering the small cohort size, results must be interpreted with caution, however statistical analyses revealed elevated urinary non-adjusted 8-OHdG levels in the 1st trimester of mothers that delivered boys compared to those who delivered girls (p < 0.01). Increased urinary non-adjusted 8-OHdG concentrations at the time of delivery were significantly associated with clinical records (any type of clinical record during pregnancy; p < 0.05). The novel extraction and analytical method for the assessment of 8-OHdG is applicable for sensitive analysis of multiple analytes or biomarkers in urine matrix. This method could also be applied for other matrices such as blood or tissues. Our findings show that 8-OHdG in urine of pregnant women could predict oxidative stress in placenta and can be related to characteristics such as maternal obesity, mode of delivery and newborn sex.

• Klíčová slova
• 8-OHdG, Oxidative stress, Placenta, Pregnancy, Urine,
• MeSH
• 8-hydroxy-2'-deoxyguanosin MeSH
• biologické markery moč   MeSH
• chromatografie kapalinová metody   MeSH
• deoxyguanosin * moč   MeSH
• kreatinin moč   MeSH
• lidé MeSH
• novorozenec MeSH
• oxidační stres MeSH
• placenta MeSH
• poškození DNA MeSH
• tandemová hmotnostní spektrometrie metody   MeSH
• těhotenství MeSH
• těhotné ženy * MeSH
• Check Tag
• lidé MeSH
• mužské pohlaví MeSH
• novorozenec MeSH
• těhotenství MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• Názvy látek
• 8-hydroxy-2'-deoxyguanosin MeSH
• biologické markery MeSH
• deoxyguanosin * MeSH
• kreatinin MeSH