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COVID-19 can cause a range of complications, including cardiovascular, renal, and/or respiratory insufficiencies, yet little is known of its potential effects in persons exposed to toxic metals. The aim of this study was to answer this question with in silico toxicogenomic methods that can provide molecular insights into COVID-19 complications owed to exposure to arsenic, cadmium, lead, mercury, nickel, and chromium. For this purpose we relied on the Comparative Toxicogenomic Database (CTD), GeneMANIA, and ToppGene Suite portal and identified a set of five common genes (IL1B, CXCL8, IL6, IL10, TNF) for the six metals and COVID-19, all of which code for pro-inflammatory and anti-inflammatory cytokines. The list was expanded with additional 20 related genes. Physical interactions are the most common between the genes affected by the six metals (77.64 %), while the dominant interaction between the genes affected by each metal separately is co-expression (As 56.35 %, Cd 64.07 %, Pb 71.5 %, Hg 81.91 %, Ni 64.28 %, Cr 88.51 %). Biological processes, molecular functions, and pathways in which these 25 genes participate are closely related to cytokines and cytokine storm implicated in the development of COVID-19 complications. In other words, our findings confirm that exposure to toxic metals, alone or in combinations, might escalate COVID-19 severity.

This study aimed to assess the redox status and trace metal levels in 49 shoe industry workers (11 men and 38 women) occupationally exposed to a mixture of volatile organic compounds (VOCs), which includes aliphatic hydrocarbons, aromatic hydrocarbons, ketones, esters, ethers, and carboxylic acids. All measured VOCs were below the permitted occupational exposure limits. The control group included 50 unexposed participants (25 men and 25 women). The following plasma parameters were analysed: superoxide anion (O2•−), advanced oxidation protein products (AOPP), total oxidative status (TOS), prooxidant-antioxidant balance (PAB), oxidative stress index (OSI), superoxide dismutase (SOD) and paraoxonase-1 (PON1) enzyme activity, total SH group content (SHG), and total antioxidant status (TAS). Trace metal levels (copper, zinc, iron, magnesium, and manganese) were analysed in whole blood. All oxidative stress and antioxidative defence parameters were higher in the exposed workers than controls, except for PON1 activity. Higher Fe, Mg, and Zn, and lower Cu were observed in the exposed vs control men, while the exposed women had higher Fe and lower Mg, Zn, and Cu than their controls. Our findings confirm that combined exposure to a mixture of VOCs, even at permitted levels, may result in additive or synergistic adverse health effects and related disorders. This raises concern about current risk assessments, which mainly rely on the effects of individual chemicals, and calls for risk assessment approaches that can explain combined exposure to multiple chemicals.

The link between environmental pollution and obesity is of high importance, because understanding the relationship between the two can provide valuable insights into the complex factors contributing to the obesity epidemic. These chemicals, termed "obesogens," are believed to disrupt lipid metabolism processes, therefore promoting the development of obesity. Human activities such as industrialization, urbanization, agriculture, and transportation have significantly contributed to environmental pollution. Therefore, the main identified obesogens are BPA found in plastics, food packaging, and thermal paper receipts, phthalates, commonly used in plastics, personal care products, and food packaging, toxic metal(oid)s, determined in non-stick cookware, water-resistant fabrics, and food packaging, pesticides, used in agriculture, as well as other persistent organic pollutants (POPs), and pharmaceuticals (waste). Addressing environmental pollution not only has the potential to improve environmental quality, but also to promote public health and prevent obesity-related diseases. Addressing the causality between pollutants and obesity could be a new and challenging road map for health professionals.

This study aimed to investigate the effect of 150 mg/L sodium fluoride (NaF) on redox status parameters and essential metals [copper (Cu), iron (Fe), and zinc (Zn)] in the blood, liver, kidney, brain, and spleen of Wistar rats and to determine the protective potential of selenium (Se) against fluoride (F-) toxicity. Male Wistar rats were randomly distributed in groups of five (n=5) receiving tap water (control) or water with NaF 150 mg/L, NaF 150 mg/L + Se 1.5 mg/L, and Se 1.5 mg/L solutions ad libitum for 28 days. Fluorides caused an imbalance in the redox and biometal (Cu, Fe, and Zn) status, leading to high superoxide anion (O2 .-) and malondialdehyde (MDA) levels in the blood and brain and a drop in superoxide dismutase (SOD1) activity in the liver and its increase in the brain and kidneys. Se given with NaF improved MDA, SOD1, and O2 .- in the blood, brain, and kidneys, while alone it decreased SH group levels in the liver and kidney. Biometals both reduced and increased F- toxicity. Further research is needed before Se should be considered as a promising strategy for mitigating F- toxicity.

Considering that some researchers point to a possible influence of air pollution on COVID-19 transmission, severity, and death rate, the aim of our in silico study was to determine the relationship between the key air pollutants [sulphur dioxide (SO), carbon monoxide (CO), 2particulate matter (PMx), nitrogen dioxide (NO2), and ozone (O3)] and COVID-19 complications using the publicly available toxicogenomic analytical and prediction tools: (i) Comparative Toxicogenomic Database (CTD) to identify genes common to air pollutants and COVID-19 complications; (ii) GeneMANIA to construct a network of these common and related genes; (iii) ToppGene Suite to extract the most important biological processes and molecular pathways; and (iv) DisGeNET to search for the top gene-disease pairs. SO2, CO, PMx, NO2, and O3 interacted with 6, 6, 18, 9, and 12 COVID-19-related genes, respectively. Four of these are common for all pollutants (IL10, IL6, IL1B, and TNF) and participate in most (77.64 %) physical interactions. Further analysis pointed to cytokine binding and cytokine-mediated signalling pathway as the most important molecular function and biological process, respectively. Other molecular functions and biological processes are mostly related to cytokine activity and inflammation, which might be connected to the cytokine storm and resulting COVID-19 complications. The final step singled out the link between the CEBPA gene and acute myelocytic leukaemia and between TNFRSF1A and TNF receptor-associated periodic fever syndrome. This indicates possible complications in COVID-19 patients suffering from these diseases, especially those living in urban areas with poor air quality.

Mercury (Hg) is one of the most important environmental pollutants with endocrinedisrupting properties. There is little data from epidemiological studies describing the doseresponse relationship between toxic metal levels and hormone levels. The aim of this study was to use the nearest neighbor matching analysis to determine the difference in Hg concentration in healthy/sick subjects with thyroid disease and to use Benchmark modeling to determine the doseresponse relationship between Hg levels in the blood and thyroid-stimulating hormone (TSH) and thyroid hormones in serum. Blood samples were collected and used for Hg measurement using the ICP-MS method, and separated serum was used for hormone analysis. The study showed the existence of a statistically significant difference in Hg levels measured in healthy and sick subjects and the existence of a dose-response relationship between Hg and all measured hormones, with a narrow interval obtained for the Hg-TSH pair. The results of this research support the use of the Benchmark dose approach for the purpose of analyzing data from human studies, and our further research will be focused on examining the impact of low doses on animal models in order to determine more precise effects of low doses on the organism.

While experimental animal investigation has historically been the most conventional approach conducted to assess drug safety and is currently considered the main method for determining drug toxicity, these studies are constricted by cost, time, and ethical approvals. Over the last 20 years, there have been significant advances in computational sciences and computer data processing, while knowledge of alternative techniques and their application has developed into a valuable skill in toxicology. Thus, the application of in silico methods in drug safety assessment is constantly increasing. They are very complex and are grounded on accumulated knowledge from toxicology, bioinformatics, biochemistry, statistics, mathematics, as well as molecular biology. This review will summarize current state-of-the-art scientific data on the use of in silico methods in toxicity testing, taking into account their shortcomings, and highlighting the strategies that should deliver consistent results, while covering the applications of in silico methods in preclinical trials and drug impurities toxicity testing.

Cadmium (Cd), one of the most abundant environmental pollutants, is considered to have endocrine disrupting properties. However, data on the dose-response relationship between Cd dose and levels of hormones have been insufficiently studied, especially in human data sets. Thus, the aim of this study was to determine the possibility of analyzing data obtained from a case-control study in female patients with benign/malignant breast tumors, using the Benchmark dose (BMD) concept. The collected data on Cd levels in breast tissue and estrogen serum levels were processed in PROAST software using different variables. The dose-response relationship between the internal dose of Cd and estradiol levels in the serum was investigated and BMD intervals were calculated. The dose-response relationship between the Cd concentration in breast tissue and the estradiol serum level was shown, indicating lower estradiol serum levels as a consequence of higher Cd concentrations in breast tissue. As one of the few studies analyzing human data using the BMD approach, these findings could have a pivotal role in dose response analysis of data collected from human studies.

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Most Pb and Cd neurotoxicity studies investigate exposure to either of the toxic metals alone, while data on co-exposure are scarce. The aim of our study was to fill that gap by investigating acute combined effects of Pb and Cd on redox and essential metal status in the brain of Wistar rats. Animals were randomised in four groups of six to eight rats, which received 15 or 30 mg/kg of Cd, 150 mg/kg of Pb, or 150 mg/kg of Pb + 15 mg/kg of Cd by gavage. The fifth, control, group received distilled water only. Co-treatment with Pb and Cd induced significant increase in malondialdehyde (MDA) and thiobarbituric acid-reactive substances (TBARS) compared to control and groups receiving either metal alone. This is of special importance, as MDA presence in the brain has been implicated in many neurodegenerative disorders. The groups did not significantly differ in Zn, Cu, Mn, and Fe brain levels. Our findings highlight the importance of metal mixture studies. Neurotoxicity assessments of single chemicals do not provide a real insight into exposure to mixtures in real life. Further research should look into interactions between these metals to reveal complex molecular mechanisms of their neurotoxicity.

Immunochromatographic strips for urine drug screening tests (UDSTs) are common and very suitable for drug abuse monitoring, but are also highly susceptible to adulterants kept in the household, which can significantly alter test results. The aim of this study was to see how some of these common adulterants affect UDST results in practice and whether they can be detected by sample validity tests with pH and URIT 11G test strips. To this end we added household chemicals (acids, alkalis, oxidizing agents, surfactants, and miscellaneous substances) to urine samples positive for amphetamine, 3,4-methylenedioxymethamphetamine (MDMA), tetrahydrocannabinol, heroin, cocaine, or benzodiazepines (diazepam or alprazolam) and tested them with one-component immunochromatographic UDST strips. The UDST for cocaine resisted adulteration the most, while the cannabis test produced the most false negative results. The most potent adulterant that barely changed the physiological properties of urine specimens and therefore escaped adulteration detection was vinegar. Besides lemon juice, it produced the most false negative test results. In conclusion, some urine adulterants, such as vinegar, could pass urine specimen validity test and remain undetected by laboratory testing. Our findings raise concern about this issue of preventing urine tampering and call for better control at sampling, privacy concerns notwithstanding, and better sample validity tests.

Introduction/Objective. The aim was to assess the effect of oxidative stress parameters on sperm count, motility, and morphology of spermatozoa, and the influence of different semen parameters on the outcome of in vitro fertilization (IVF) procedure – the number of fertilized oocytes, fertilization, and pregnancy rate of female partners. Method. In 52 male patients superoxide dismutase (SOD), malondialdehyde (MDA), and sulfhydryl (-SH) groups were determined in serum, before beginning the IVF cycle. Semen samples were collected after 2–3 days of sexual abstinence. Results. Patients were divided into two groups, the normozoospermic, and those with pathological sperm findings. The second group was divided into oligozoospermic, asthenozoospermic, and teratozoospermic groups. SOD activity was lower, while MDA and -SH groups, while not significantly, was higher in groups with sperm parameter disorders. Fertilization rate was significantly lower in the group of asthenozoospermia and teratozoospermia (p = 0.034), as well as delivery rate (p = 0.020). The group with oligozoospermia had significantly lower delivery rate (p = 0.013). Conclusion. Our study found higher fertilization and delivery rate in men with normozoospermia. However, no significant correlation between OS markers and semen parameters was found. [Project of the Serbian Ministry of Education, Science and Technological Development, Grant no. III46009]

This paper aims to present the importance of the benchmark dose (BMD) as a point of departure (the lowest dose or concentration in the experiment that deviates from the response that differs from the normal response) in toxicological risk assessment, as well as to present commonly used software for its calculation (BMDS and PROAST). Benchmark dose is defined as a statistical lower confidence limit of a dose that results in a small change in effect (5-10%) in comparison with the control value. The BMD approach is considered a substitution for the NOAEL approach, which uses the highest observed no-effect level (NOAEL) to obtain the reference dose. The BMD approach is a methodically more forward-thinking technique than the NOAEL approach because it has statistical power and provides a wide range of dose-response relationships and allows the determination of their uncertainty and variability. Moreover, the BMD approach contributes to the reduction of experimental animals in toxicity studies. Therefore, the European Food Safety Authority (EFSA) recommends the use of BMDL10 values for quantal and BMDL05 for continuous data.

For over a century, one of the main toxicologists' goals was finding the relationship between the chemical structure and toxicity. The development of computer technologies has lead to the production of software models that could be applied for this purpose. However, use of in silico methodology in toxicology is very complex. Having in mind that toxic effect occurs through multiple mechanisms on different tissues and organs, creating software that can make reliable toxicity predictions is very complicated. In silico methods found the application in toxicity assessment of substances for which data obtained from traditional toxicity tests is lacking (metabolites, drug impurities, etc.). Also, in silico methods can be used in the process of chemical synthesis, with the aim of designing safer chemicals. Currently, in silico methods for toxicity predictions are most commonly used along with standard toxicological tests, with a tendency to replace in vitro and in vivo toxicity tests in the future. This paper will present the strengths and limitations of commonly used software in in silico toxicology (OECD QSAR Toolbox, Derek Nexus, ToxTree i MultiCASE).