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The paper deals with industrial chemical safety with a focus on major chemical accidents, hazardous chemicals and mixtures with emphasis on the dangers of selected sub-limit sources of risk. Currently, the two main laws in force, the Major Accident Prevention Act of 2015 (1), or the so-called "Chemicals Act" or the Chemicals and Mixtures Act of 2011 (2), have failed to address the serious safety issues of the so-called "Sub-threshold sources of risk" consisting of the low masses of hazardous chemicals.
Until 2017, there was no clearly defined professional methodology, procedure or other tool to assess risk assessment of sources with hazardous chemicals and mixtures.
The main part briefly mentions the instruction of the General Director of the Fire and Rescue Service of the Czech Republic (Instruction 35/2017 (3)), which solves the issue very well and provides professional and methodological instructions for capturing and evaluating sub-limit sources of risk. This clearly improves the prevention of these events, it also increases the preparedness for possible emergency releases of hazardous substances and, last but not least, it can also increase the preparedness of the population for the correct response to releases of below-limit amounts of certain hazardous substances.

Enrofloxacin and marbofloxacin are two veterinary fluoroquinolones used to treat severe bacterial infections. The release of fluoroquinolones in the environment is mainly due to the direct discharge of aquaculture products and the excretion in urine and feces of livestock animals. It results in the contamination of soil, surface water, sediment, ground water and biota.
We focused on acute and reproductive effects of enrofloxacin and marbofloxacin, in particular. Assessment of the impact of selected antibiotics on important representatives of the aquatic environment. The aim of this study was to investigate the chronic toxicity of the antibiotics to Daphnia magna and Tubifex tubifex. Selected representatives are an important part of the fish food chain. The effect was tested on the growth and reproduction of D. magna in a chronic test scenario according to OECD guidelines 211. Tests with Tubifex tubifex were performed according to method ASTM E1706-04. We also performed an acute toxicity test with Danio rerio. The experiment was performed according to the Guideline for Test No. 236: Fish Embryo Acute Toxicity (OECD 2013). We observed mortality, malformation, hatching rate and heartbeat.  Graphpad Prism was used for data visualization and statistics. Dose-response curves were constructed and EC50 values were calculated. In particular, changes in the behaviour of test organisms were noted.

Phytic acid (IP6) is the most abundant inositol phosphate in nature present in plants as well as in mammalian cells, thus, IP6 is common part of human diet. IP6 has been considered for a long time as an antinutritional component due to its ability to bound minerals and affect their bioavailability in gastrointestinal tract (1). On the other hand, the protective effects of IP6 have been reported in pathological conditions including neurodegenerative diseases, cardiovascular diseases and cancer, likewise, a hepatoprotective effect has been observed (2). Cytochromes P450 (CYPs) are key enzymes involved in the metabolism of 70-80% of all clinically used drugs and they are responsible for variability in drug response. Expression of CYPs is affected by many factors and can be regulated by specific nuclear receptors such as aryl hydrocarbon receptor (AhR) and pregnane X receptor (PXR). To date, variety of diet-derived metabolites, have been identified as ligands of these receptors showing that different diet habits may contribute to interindividual differences in CYP activity.
In our study, the effect of IP6 on CYPs expression and enzymatic activity was assessed using different hepatic cell models. We have found that mRNA expression of CYP2B6, CYP2E1 and CYP3A4 was significantly downregulated by 10μM IP6 in primary human hepatocytes.
Therefore, further studies are needed to evaluate the complex functions of IP6 and its possible interaction with drug metabolism in order to translate its promising therapeutic potential to clinical practice.

Neonicotinoid insecticide acetamiprid is a part of relatively frequently used commercial formulations such as Mospilan 20SP or newly developed Carnadine, Kestrel and others. The popularity of these insecticides lies in their ease of handling and high efficacy in treating canola, corn, potatoes and apple trees. However, the possibility that pesticide products could also affect non-target organisms still needs to be taken into account. For this reason, the aim of our work was to assess the possible cytotoxic and genotoxic effects of acetamiprid-based insecticide Mospilan 20SP, which is one of the well-known commercially available formulations. Conventional tests such as chromosomal aberration assay and comet assays (alkaline and neutral) were employed under in vitro conditions using cultures of bovine whole blood cells and isolated bovine lymphocytes. The insecticide formulation was dissolved in pure water to prepare quantities of 5, 10, 25 and 50 μg.mL^-1 for analysis after 2 h, 24 h and 48 h of exposure, respectively. After 24 h of exposure, values of mitotic indices showed a decrease in mitotic activity of cells (p<0,05; p<0,01) depending on increasing concentrations. The 24 h exposure to pesticides also showed an increase in chromatide and chromosome breaks in a dose-dependent manner for the insecticide under study (p<0.05; p<0.01) compared to the negative control. Alkaline and neutral comet tests revealed the potential of acetamiprid-based formulation to induce DNA damage in bovine cells.

Rivastigmine is a pseudo-irreversible cholinesterase inhibitor used for therapy of Alzheimer´s disease and non-Alzheimer dementia syndromes. In humans, rivastigmine can cause significant gastrointestinal side effects that can limit its clinical use. The aim of this study was to assess the impact of rivastigmine on gastric motor function by means of electrogastrography (EGG) in experimental pigs. Six experimental adult female pigs (3-month-old; mean weight 30.7±1.2 kg) were enrolled into the study twice and created two experimental groups. In group A, a single intragastric dose of 6 mg rivastigmine hydrogen tartrate was administered in the morning to fasting pigs before EGG recording. In group B, rivastigmine was administered to overnight fasting animals in a dietary bolus in the morning for 7 days (6 mg per day). On day 8, an intragastric dose of 12 mg rivastigmine was given in the morning to fasting pigs before EGG. EGG recording was accomplished by means of an EGG standalone system. Recordings from both groups were evaluated in dominant frequency and EGG power (areas of amplitudes). In total, 1,980 one-minute EGG intervals were evaluated. In group A, basal EGG power (median 1290.5; interquartile range 736.5-2330 μV²) was significantly higher in comparison with the power of intervals T6 (882; 577-1375; p=0.001) and T10 (992.5; 385-2859; p=0.032). In group B, the dominant frequency increased significantly from basal values (1.97±1.57 cycles per minute) to intervals T9 (3.26±2.16; p<0.001) and T10 (2.14±1.16; p=0.012), respectively. In group B, basal EGG power (median 1030.5; interquartile range 549-5093) was significantly higher in comparison with the power of intervals T7 (692.5; 434-1476; p=0.002) and T8 (799; 435-1463 μV²; p=0.004). In conclusion, both single as well as repeated intragastric administration of rivastigmine hydrogen tartrate caused a significant decrease of EGG power (areas of amplitudes) in experimental pigs. EGG power may serve as an indirect indicator of gastric motor competence. These findings provide a possible explanation of rivastigmine-associated dyspepsia in humans.

The nerve agents of the A-series are relatively recent chemical weapons with no antidote available yet (1). Once inside the human body, those chemicals act similarly to the classic nerve agents, by binding to the catalytic residue Serine 203 (Ser203) of human acetylcholinesterase (HssAChE) and thus preventing the proper function of this enzyme. However, there is no experimental evidence yet if the current antidotes for intoxication by nerve agents are also capable of restoring AChE inhibited by the nerve agents of the A-series. In order to launch some light on this issue, we used computational techniques (molecular docking, molecular dynamics and MM-PBSA interaction energy calculations) to assess the performances of the four currently available commercial oximes (2-PAM, HI-6, obidoxime and trimedoxime) when in contact with HssAChE inhibited by the agent A-242 (2). Based on the near-attack conformation (NAC) criterion, our results suggest that the commercial oximes would have limited efficacy to reactivate the enzyme since they are not able to properly approach the adduct Ser203-A-242. Among those oximes, trimedoxime seems to be the most promising, since it showed lower values of energy in the MM-PBSA calculations, a higher stability inside the catalytic anionic center (CAS) of HssAChE and was able to adopt a position closer to the NAC that could enable the reactivation mechanism.

The thyroid hormone regulation is a vital and complex process for proper organism function that involves multiple organs across species. A disruption of the thyroid hormone system (THS) by endocrine disruptors (EDs) can be linked with adverse effects such as developmental and autoimmune disorders. However, THS has been rather neglected, even though EDs have been gaining attention recently. Currently, the H2020 ERGO project aims to develop a battery of high-throughput in vitro bioassays based on molecular initiating events (MIEs) in the adverse outcome pathway network connected to THS disruption (tAOP) to narrow the knowledge gap.
The thyroid hormone (TH) activity may be disrupted on several levels including synthesis, transport, metabolism, and receptor (trans)activation. To evaluate the suitability of various in vitro models for studying different endpoints, these have been characterized regarding the expression of the set of genes corresponding to MIEs in tAOP. Moreover, we developed a set of in vitro transfected HEK-293T cell lines overexpressing genes of major interest, i.e., deiodinases type 1-3 (DIO1-3), natrium-iodide symporter (SLC5A5; NIS) and thyroid peroxidase (TPO). Next to this, we adopted and optimized bioassays for thyroxine/transthyretin (T4/TTR) displacement, aryl hydrocarbon receptor (AhR), and thyroid receptor (TR) activation and characterized the potential of selected human exposure-relevant compounds to disrupt prioritized MIEs.

The Cytomegalovirus (CMV) pass through placenta is connected with consequences in prenatal as well as postnatal phase of development. Newborns can be asymptomatic, can have mild or even life-threating symptoms with serious long-term sequels. All CMV infected newborns are at risk of long-term neurodevelopmental problems and sensorineural hearing problems.
The aim of the work: To analyse prenatal and postnatal characteristics, clinical and laboratory findings, results of investigations in the group of 11 newborns with congenital CMV infection, who were hospitalized at Neonatal Department of Intensive Medicine between January 1st 2012 and March 31st, 2022 included.
Results: Prenatal foetal sonography revealed in patient 5 and 8 positive calcifications in brain; in patient 6, 9 and 11 isolated ventriculomegaly was found. Neurological examination was clinically negative in patient 1 and 10, changes of muscular tonicity and spontaneous activity was confirmed in the rest of group. In patient 5 and 10 one-sided positivity of otoacoustic emissions was confirmed. Chorioretinitis with bilateral negative otoacoustic emissions was confirmed in patient 5. Clinical status of patient 11 was complicated by pneumonitis. Three patients were treated with antiviral drugs orally, and 11 newborns had combination of intravenous and oral form of treatment.
Conclusion: The results of analysis will contribute to a society-wide solution of prevention. Monitoring of the frequency of CMV infection in population with education of population can decreased the number of affected newborns.

Bisphenol A (BPA), a widely used plastic additive with proven endocrine disrupting properties, has been previously linked to reproductive system disorders and tumors. Due to such harmful effects, its use has become restricted but other bisphenol (BP) analogs have been introduced as replacements for BPA usage in many applications. However, little is known about their biological actions or about similarities with the actions of the prototype BPA. The present study used the human prostate cell lines: androgen-unresponsive PC3 cells and androgen-responsive LNCaP cells, to examine effects of bisphenols AF, S, F and B, in comparison to BPA. We focused on BP effects on cell viability, proliferation, and oxidative stress (concentrations 10^-10–10^-4M) at several time points. We observed different sensitivity of both cell lines to toxic effects of the individual analogs. Although the highest concentration of each of the five BPs inhibited cell proliferation (BrdU incorporation) in both cell lines, this resulted in viability decrease only in LNCaP cells while in PC3 cells, the viability remained unaffected (MTS assay). The exception was observed in the presence of the BPAF analog with the profound cytotoxic effects, which seem to be caused by the early apopotic actions and increase in caspase activity (fluorescent assay). In addition, the highest concentration of each BP analog elevated reactive oxygen species production by the prostate cells. The results show that high concentrations of BPs can affect prostate cancer cell status and that androgen-responsive LNCaP cells are significantly more sensitive than the unresponsive PC3 cells, what indicates possible involvement of androgen receptors in the action of BP derivatives, and will be a subject of further elucidation.

Preclinical studies in experimental pigs are carried out mostly under general anaesthesia. Ketamine is commonly used for introduction to anaesthesia. However, concerns exist, whether ketamine, an NMDA-receptor antagonist, influences gastric motor function. The aim of this study was to investigate porcine gastric myoelectric activity by means of electrogastrography (EGG). Seventeen female animals (mean weight 36.2±3.8 kg) were enrolled. Drugs used as an introduction to anaesthesia were: Group A (n=5): medetomidine 0.1 mg/kg i.m.; butorphanol 0.3 mg/kg i.m.; midazolam 0.3 mg/kg i.m.; Group B (n=6): azaperon 2.2 mg/kg i.m.; Group C (n=6): ketamine 20 mg/kg i.m.; azaperon 2.2 mg/kg i.m., all groups followed by i.v. propofol (repeated one-mL-boluses, 10-12 mL in total). EGG recording started 15 min. after the introduction administration and lasted 30 min. Results were evaluated as dominant frequency of gastric slow waves (DF) and EGG power (areas of amplitudes). In total, 510 one-minute EGG intervals were assessed. DFs were (mean ± standard deviation): 1.4±0.4 (Group A), 1.3±0.3 (Group B) and 0.2±0.1 cycles per min. (Group C). The difference between group C and groups A and B was statistically significant (p<0.001). Median power (IQR) was 0.13 (0.02-0.44; Group A), 0.13 (0.03-0.54; Group B) and 0.30 V^2 (0.07-1.44; Group C). The difference between groups A and C was of borderline significance (p=0.066; type 2 error beta 0.295). In conclusion, ketamine, even in a single low-dose, affected myoelectric function of the porcine stomach. Therefore, it should be avoided in gastrointestinal motility studies in experimental pigs.

Atopic dermatitis (AD) is a chronic inflammatory skin disease, which is still not fully understood. Crucial roles in the pathogenesis play Th2 immune response dysregulation and epidermal barrier alterations. Defects of this skin barrier have been considered in the initial step of AD development. Inflammatory skin conditions AD have a negative wide-ranging impact on a patient’s life quality. However, testing methods and/or treatment options for this disease are unsatisfactory nowadays.
To study the anti-inflammatory effect of substances on AD pathogenesis we established inflammatory models by stimulating HaCaT cells with tumor necrosis factor-α (TNF-α) and interferon-γ (IFN-γ). We designed two different treatment models (pre- and post-treatment) to mimic keratinocytes ̓ inflammatory conditions of AD that simulate relapse and therapy. HaCaT cells are a suitable model to follow the release of inflammatory mediators interleukin-6 (IL-6) and interleukin-8 (IL-8) in response to TNF-α and IFN-γ treatment. The AD-like models were verified by using natural flavonoid quercetin and synthetic glucocorticoid dexamethasone. Both substances should be associated with the inhibition of inflammatory cytokines production in the skin. Based on the data obtained, these models could open the way for screening of new preventive or therapeutic AD agents. The details of the experiments will be discussed in our poster contribution.

Melanins are heterogeneous polymeric dark pigments colored in black with relatively diverse properties, functions and rather non-defined structure. Many of commercially available melanins used in scientific studies have been produced synthetically or isolated from natural sources (1, 2).
We studied two types of melanin, i.e. commercially available synthetic melanin (SM) and biotechnologically obtained bacterial melanin (BM) from Bacillus thuringiensis. The topical aim of our study was to estimate the biological effects of both melanins in the neuroblastoma SH-SY5Y cell line. After melanin treatment (0-200 μg/mL), cell viability, glutathione levels (3) and cell respiration were assessed.
Both melanins were structurally characterized in detail and BM was more hydrophilic. After melanin treatment of SH-SY5Y cells, we found that SM at similar dosage caused always larger cell impairment compared to BM. In addition, more severe toxic effect of SM was found in mitochondria. In general, we conclude that more hydrophilic BM induces lower cell impairment in comparison to SM. Although additional elucidation of the toxicity mechanism is needed, it seems that the difference in level of toxicity induced by melanins can be dependent on their water solubility. Our findings can be usable for neuroscientific studies estimating the potential use for study of neuroprotection or neuromodulation.