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This paper presents test results of the impact of chemical admixtures used in the underwater concrete technology, i.e. a superplasticizer (SP), an anti-wash admixture (AWA) and SiO2 nano- particles (NP) on the cement hydration process, rheological properties and the setting time. The impact of admixtures was tested in combination and separately, with the use of microcalimetry, X-ray diffraction (XRD) and rheology. It was demonstrated that AWA and SP admixtures caused a delay of the hydration process, while the impact of SP was much greater. The above statement was also confirmed by results of rheological tests. Combined application of AWA, SP and NP causes even a larger delay of the hydration process and the increase of paste rheological parameters, with the impact of the superplasticizer particularly visible.

In this work, the evaluation of measurement uncertainty of concrete dynamic elastic modulus testing method was conducted. The dynamic test was carried out using impulse excitation and modal analysis method, which can be used to determine the compressive strength of concrete in a non-destructive way. The tests were conducted using concrete samples in order to determine the practical usefulness of the mentioned method. It has been demonstrated that the impulse excitation and modal analysis method is characterized by very good repeatability.

This study performed advanced toxicological assessments of the new substance AP-238 using nine 'green' in silico methods, focusing on acute toxicity, organ-specific effects, skin and eye irritation, genetic toxicity, and cardiotoxicity. A quantitative assessment of AP-238's acute toxicity (AT) was performed by predicting theoretical LD 50 values for both rats and mice across different administration routes using various in silico methods. Results indicated the highest toxicity via intravenous administration in mice, with a t-LD 50 of 53 mg/kg, while oral administration in rats exhibited a lower toxicity range, with t-LD 50 values between 666.43 and 1838.77 mg/kg, depending on the predictive model used. The identification of toxicophores (the fragment connecting the benzene ring to the piperazine ring, including the α, β, and γ carbon atoms near the nitrogen atom) in AP-238 suggests a high likelihood of lung toxicity (61%), with additional risks to the cardiovascular (58%) and renal systems (56%), emphasizing specific molecular fragments associated with these adverse effects. Genotoxic evaluations presented a mixed view, with low to moderate probabilities of a positive Ames test, suggesting some uncertainty but generally indicating a reduced risk of genetic toxicity. Eye and skin irritation risks were deemed minimal, supported by several models with high confidence. Cardiotoxicity assessments revealed varied information on the potential effects of AP-238 on the hERG channel, with some studies suggesting a nonsignificant impact, while others indicated moderate risk, although with low reliability in the predictions. This highlights the nuanced challenges in assessing the safety of novel substances through 'green' in silico methods., Competing Interests: Declarations. Competing interests: The authors declare no competing interests., (© 2024. The Author(s).)

Bromo-DragonFLY is a synthetic new psychoactive substance (NPS) that has gained attention due to its powerful and long-lasting hallucinogenic effects, legal status, and widespread availability. This study aimed to use various in silico toxicology methods to predict key toxicological parameters for Bromo-DragonFLY, including acute toxicity (LD 50 ), genotoxicity, cardiotoxicity, health effects, and the potential for endocrine disruption. The results indicate significant acute toxicity with noticeable variations across different species, a low likelihood of genotoxic potential suggesting potential DNA damage, and a notable risk of cardiotoxicity associated with inhibition of the hERG channel. Evaluation of endocrine disruption suggests a low probability of Bromo-DragonFLY interacting with the estrogen receptor α (ER-α), indicating minimal estrogenic activity. These insights from in silico investigations are important for advancing our understanding of this NPS in forensic and clinical toxicology. These initial toxicological examinations establish a foundation for future research efforts and contribute to developing risk assessment and management strategies for using and misusing NPS.

Strawberry is one of the most commonly eaten berries. Breeding procedures led to the separation of two types of strawberries: June - bearing and Ever-bearing strawberries fruit for about a month and Ever - bearing throughout the growing season. The aim of the project is to compare the antioxidant parameters between both types of strawberries with those of two other dicots (blackberry and red raspberry). The research covered 29 strawberry clones: 10 Ever - bearing and 19 June - bearing, 6 blackberries, and 12 red raspberry. Statistical analysis of the Mann-Whitney U test showed that in terms of the tested parameters there are no statistical differences between the two types of strawberries; however, the year-round yield and extended availability of fresh fruit mean that these varieties are gaining more and more interest from producers and consumers. Repeat-fruiting strawberries are statistically more than twice as efficient than traditional varieties, not inferior in taste to traditional varieties.

The presence of heavy metals in food products may seem an archaic concern; however, our study reveals that the risk is significant, unexpectedly in Food for Special Medical Purposes (FSMP) for oncology patients available in Polish pharmacies. This investigation fills that gap through a detailed toxicological analysis and health risk assessment of these heavy metals in FSMP products (n = 23) using inductively coupled plasma mass spectrometry (ICP-MS). Our comprehensive risk assessment involved evaluating (1) the concentrations of As, Cd, Hg, and Pb in both liquid and powdered FSMP formulations, (2) the amount of heavy metals ingested per serving as specified by the manufacturer, and (3) the cumulative daily and weekly intake adjusted for body weight, benchmarked against the provisional tolerable weekly intake (PTWI). While most samples were below PTWI limits, Cd levels raised concerns due to potential cumulative exposure risks, particularly for oncology patients consuming these products regularly. This study underscores the hidden dangers of heavy metal contamination in FSMP, emphasizing the need for vigilant monitoring and stringent regulatory frameworks to ensure patient safety. By uncovering these latent risks through meticulous toxicological assessment, our research provides crucial insights that could safeguard vulnerable populations. This study is significant due to concerns related to the complex risk assessment of FSMP for cancer patients, considering the complexity of oncological diseases and other comorbid factors, as well as the verification of available legal and regulatory acts of FSMP at the European Community level., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier Ltd. All rights reserved.)

This study focuses on FSMPs for oncologic patients, specifically analyzing the toxicological profiles of nickel (Ni), chromium (Cr), and selenium (Se) within these products available in Polish pharmacies. The presence of these elements was quantified using inductively coupled plasma mass spectrometry (ICP-MS). Results indicated variations in the concentrations of Ni, Cr, and Se across different FSMP samples, with some products exceeding the acceptable limits set by regulatory guidelines. The study highlights the potential health risks associated with nickel exposure, including dermatitis and carcinogenesis, and the complex roles of chromium and selenium, which can be both beneficial and harmful depending on their levels. Our findings reveal significant variability in the elemental content across different FSMP products, i.e.: Ni: 0.155-25.488 μg/portion, Cr: 0.076-28.726 μg/portion and Se: 0.083-20.304 μg/portion). Notably, selenium levels in FSMPs showed considerable discrepancies compared to manufacturers' declarations, averaging only about 20% of the stated values. Regulatory assessments based on the Acceptable Daily Intake (ADI) and Permitted Daily Exposure (PDE) descriptors indicated that the estimated weekly intake of Ni, Cr, and Se from these FSMPs did not exceed the provisional tolerable weekly intake (PTWI) values. However, the highest Ni content was 30.58% of the PTWI, raising concerns about potential health risks, including dermatitis and carcinogenesis. The results for Cr underscored the necessity for careful monitoring due to its potential toxic effects. Selenium, despite its essential role, showed levels inadequate to meet the Recommended Dietary Allowance (RDA), potentially impacting its intended health benefits., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier Ltd. All rights reserved.)

This study represents the first application of in silico methods to evaluate the toxicity of 4-methylphenidate (4-Mmph), a new psychoactive substance (NPS). Using advanced in silico toxicology tools, it was feasible to anticipate key aspects of 4-Mmph's toxicological profile, including acute toxicity (LD 50 ), genotoxicity, cardiotoxicity, and possible endocrine disruption. The findings indicate significant acute toxicity with variability among species, a high potential for adverse effects in the gastrointestinal system and lungs, a low genotoxic potential, a significant likelihood of skin irritation, and a notable cardiotoxicity risk associated with hERG channel inhibition. Evaluation of endocrine disruption revealed a low likelihood that 4-Mmph interacts with the estrogen receptor alpha (ER-α), indicating minimal estrogenic activity. These insights, derived from in silico studies, play a crucial role in improving the comprehension of 4-Mmph in forensic and clinical toxicology. These initial toxicological inquiries establish the foundation for future investigations and help formulate risk assessment and management strategies regarding the use and abuse of NPS. This article is part of a larger project funded by the Polish Ministry of Education and Science, titled "Toxicovigilance, Poisoning Prevention, and First Aid in Poisoning with Xenobiotics of Current Clinical Importance in Poland" (Grant Number SKN/SP/570184/2023)., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier Ltd. All rights reserved.)

Foods for Special Medical Purposes (FSMP) for oncology patients, available in pharmacies, play a crucial role in providing nutrition and supplementation. However, the scientific literature lacks comprehensive research on the safety of essential trace elements in these products. This study aimed to assess Cu, Fe, Mn and Zn levels in commonly prescribed FSMPs (n = 23) from Polish pharmacies. Using ICP-MS after microwave-induced digestion (using concentrated nitric acid and hydrogen peroxide), we evaluated element levels. Our research used three approaches: the raw score for Cu, Fe, Mn, and Zn; single intake per serving; and the daily ration, compared with the reference values of the European Food Safety Authority. Discrepancies were found between the actual and declared product compositions, influenced by the route of administration and the recommended intake. Despite variations, all products were considered safe for oncological patients based on current evidence. However, it is recommended to have clear guidelines for FSMPs in cancer care. This pioneering study evaluates the safety and quality of prescription FSMPs for cancer patients from toxicological and nutritional perspectives, highlighting the need for standardised protocols in pharmacy-dispensed FSMPs., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier Ltd. All rights reserved.)

Raman spectroscopy and Fourier transform infrared (FTIR) spectroscopy are powerful analytical techniques widely used separately in different fields of study. Integrating these two powerful spectroscopic techniques into one device represents a groundbreaking advance in multimodal imaging. This new combination which merges the molecular vibrational information from Raman spectroscopy with the ability of FTIR to study polar bonds, creates a unique and complete analytical tool. Through a detailed examination of the microscope's operation and case studies, this article illustrates how this integrated analytical instrument can provide more thorough and accurate analysis than traditional methods, potentially revolutionising analytical sample characterisation. This article aims to present the features and possible uses of a unified instrument merging FTIR and Raman spectroscopy for multimodal imaging. It particularly focuses on the technological progress and collaborative benefits of these two spectroscopic techniques within the microscope system. By emphasising this approach's unique benefits and improved analytical capabilities, the authors aim to illustrate its applicability in diverse scientific and industrial sectors.

Envenomation by marine animals poses a significant health concern globally, affecting both local residents and tourists in coastal regions. The primary objective of this review is to critically evaluate the existing scientific literature to determine the most effective first-aid treatment for envenomations caused by marine animals, specifically whether hot-water immersion (HWI) or ice-pack treatment (IPT) provides the best immediate care. This comprehensive review covers a wide range of marine envenomations, from jellyfish stings to stingray injuries. While our focus is primarily on the efficacy of HWI and IPT, we also explore the role of cold-water treatment as a result of its relevance and similarity to ice-pack applications. In addition, we examine other treatments mentioned in the literature, such as medications or vinegar, and highlight their findings where applicable. To provide a clear and structured overview, we summarised the articles in separate tables. These tables categorise the type of research conducted, the marine species studied, the region of origin of the marine species, and the key findings of each study. Our analysis of the available evidence indicates a general consensus in the scientific community on the effectiveness of HWI or IPT for envenomation by marine animals. However, when treating those injuries, it is crucial to consider all factors since there is no universally superior treatment due to the diverse nature of marine habitats.

The extensive use of rodenticides poses a severe threat to non-target species, particularly birds of prey and scavengers. In this study, a GC-MS/MS-based method was used to unlock the cause of bird deaths in Poland. Organs (liver, heart, kidney, and lungs) collected during autopsies of two rooks ( Corvus frugilegus ) and one carrion crow ( Corvus corone corone ), as well as fecal samples, were analyzed for the presence of anticoagulant coumarin derivatives, i.e., warfarin and bromadiolone. As for warfarin, the highest concentration was found in crow samples overall, with concentrations in the feces and lungs at 5.812 ± 0.368 µg/g and 4.840 ± 0.256 µg/g, respectively. The heart showed the lowest concentration of this compound (0.128 ± 0.01 µg/g). In the case of bromadiolone, the highest concentration was recorded in the liver of a rook (16.659 ± 1.499 µg/g) and this concentration significantly exceeded the levels in the other samples. By revealing the reality of the threat, these discoveries emphasize the need to regulate and monitor the trade in rodenticides.

The idea of this study was the estimation of the theoretical acute toxicity (t-LD 50 , rat, oral dose) of organophosphorus-based chemical warfare agents from the G-series (n = 12) using different in silico methods. Initially identified in Germany, the G-type nerve agents include potent compounds such as tabun, sarin, and soman. Despite their historical significance, there is a noticeable gap in acute toxicity data for these agents. This study employs qualitative (STopTox and AdmetSAR) and quantitative (TEST; CATMoS; ProTox-II and QSAR Toolbox) in silico methods to predict LD 50 values, offering an ethical alternative to animal testing. Additionally, we conducted quantitative extrapolation from animals, and the results of qualitative tests confirmed the acute toxicity potential of these substances and enabled the identification of toxicophoric groups. According to our estimations, the most lethal agents within this category were GV, soman (GD), sarin (GB), thiosarin (GBS), and chlorosarin (GC), with t-LD 50 values (oral administration, extrapolated from rat to human) of 0.05 mg/kg bw, 0.08 mg/kg bw, 0.12 mg/kg bw, 0.15 mg/kg bw, and 0.17 mg/kg bw, respectively. On the contrary, compounds with a cycloalkane attached to the phospho-oxygen linkage, specifically methyl cyclosarin and cyclosarin, were found to be the least toxic, with values of 2.28 mg/kg bw and 3.03 mg/kg bw. The findings aim to fill the knowledge gap regarding the acute toxicity of these agents, highlighting the need for modern toxicological methods that align with ethical considerations, next-generation risk assessment (NGRA) and the 3Rs (replacement, reduction and refinement) principles., (© 2024. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

This study reports the first application of in silico methods to assess the toxicity of 4-chloromethcathinone (4-CMC), a novel psychoactive substance (NPS). Employing advanced toxicology in silico tools, it was possible to predict crucial aspects of the toxicological profile of 4-CMC, including acute toxicity (LD 50 ), genotoxicity, cardiotoxicity, and its potential for endocrine disruption. The obtained results indicate significant acute toxicity with species-specific variability, moderate genotoxic potential suggesting the risk of DNA damage, and a notable cardiotoxicity risk associated with hERG channel inhibition. Endocrine disruption assessment revealed a low probability of 4-CMC interacting with estrogen receptor alpha (ER-α), suggesting minimal estrogenic activity. These insights, derived from in silico studies, are critical in advancing the understanding of 4-CMC properties in forensic and clinical toxicology. These initial toxicological findings provide a foundation for future research and aid in the formulation of risk assessment and management strategies in the context of the use and abuse of NPSs.

The emergence of Novichok agents, potent organophosphorus nerve agents, has spurred the demand for advanced analytical methods and toxicity assessments as a result of their involvement in high-profile incidents. This study focuses on the degradation products of Novichok agents, particularly their potential toxic effects on biological systems. Traditional in vivo methods for toxicity evaluation face ethical and practical constraints, prompting a shift toward in silico toxicology research. In this context, we conducted a comprehensive qualitative and quantitative analysis of acute oral toxicity (AOT) for Novichok degradation products, using various in silico methods, including TEST, CATMoS, ProTox-II, ADMETlab, ACD/Labs Percepta, and QSAR Toolbox. Adopting these methodologies aligns with the 3Rs principle, emphasising Replacement, Reduction, and Refinement in the realm of toxicological studies. Qualitative assessments with STopTox and admetSAR revealed toxic profiles for all degradation products, with predicted toxicophores highlighting structural features responsible for toxicity. Quantitative predictions yielded varied estimates of acute oral toxicity, with the most toxic degradation products being EOPAA, MOPGA, MOPAA, MPGA, EOPGA, and MPAA, respectively. Structural modifications common to all examined hydrolytic degradation products involve substituting the fluorine atom with a hydroxyl group, imparting consequential effects on toxicity. The need for sophisticated analytical techniques for identifying and quantifying Novichok degradation products is underscored due to their inherent reactivity. This study represents a crucial step in unravelling the complexities of Novichok toxicity, highlighting the ongoing need for research into its degradation processes to refine analytical methodologies and fortify readiness against potential threats., (© 2024. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

This article focusses on elucidating the toxicological profile of minoxidil, a widely used pharmacological agent for alopecia, through the application of in silico methods (Percepta ACD/Labs software). This research is driven by the need to understand key toxicological endpoints: acute toxicity, skin and eye irritation, genetic toxicity, cardiotoxicity, disruption of the endocrine system, and estimation of various health effects due to the lack of experimental data for this drug. These parameters are critically evaluated to meet the stringent requirements of the pharmaceutical industry's safety assessments. The results obtained for acute toxicity (LD 50 for rats and mouse) indicate that minoxidil exhibits a species-dependent acute toxicity profile e.g. 51 mg/kg bw for intravenous administration in mice. The predicted health effects indicate a 93% risk to the gastrointestinal system, 54% for the kidneys, 52% for the liver, 42% for the blood and lungs, and 39% for the cardiovascular system. The prediction of genotoxicity suggests a moderate probability (48%) of inducing a positive Ames test result. Furthermore, moderate inhibition of the hERG channel indicates potential cardiac risks of Minoxidil. Based on the information obtained, we propose subjecting minoxidil to additional toxicological assessments. The successful adoption of these in silico methodologies aligns with the 3 R s principle (replacement, reduction, and refinement) in the field of modern toxicological studies of minoxidil, all without the use of laboratory animals for the novelty of our toxicity assessment., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier B.V. All rights reserved.)

In recent years, the extensive exploration of Gold Nanoparticles (AuNPs) has captivated the scientific community due to their versatile applications across various industries. With sizes typically ranging from 1 to 100 nm, AuNPs have emerged as promising entities for innovative technologies. This article comprehensively reviews recent advancements in AuNPs research, encompassing synthesis methodologies, diverse applications, and crucial insights into their toxicological profiles. Synthesis techniques for AuNPs span physical, chemical, and biological routes, focusing on eco-friendly "green synthesis" approaches. A critical examination of physical and chemical methods reveals their limitations, including high costs and the potential toxicity associated with using chemicals. Moreover, this article investigates the biosafety implications of AuNPs, shedding light on their potential toxic effects on cellular, tissue, and organ levels. By synthesizing key findings, this review underscores the pressing need for a thorough understanding of AuNPs toxicities, providing essential insights for safety assessment and advancing green toxicology principles.

Plastic and rubber granules are commonly used as infill material in all-weather sports facilities, providing an ideal activity surface for millions of Europeans on a daily basis. However, concerns have been raised about the presence of hazardous elements in these granules, which can pose risks both to the environment and human health. Our study focusses on the elemental composition of rubber granules used in fall sports facilities in Rzeszów, (Podkarpackie, Poland) using field portable X-ray fluorescence (FP-XRF) as a non-destructive and 'white analytical technique'. The results show the content of Zn, Fe, Cr, Ba, Br, Ti, Cu, Cd, As, Au, Bi, Pb, Ni, Sb, and Sn in the rubber granule samples. This study highlights the need for stringent quality control measures and regulations to ensure the safety of all-weather sports facilities and protect the well-being of sportsman. When modern FP-XRF spectrometry is employed as a "white analytical technique," for the first time it becomes possible to identify the presence of hazardous elements, addressing the pressing concerns highlighted by the ECHA and enabling proactive measures to mitigate potential risks. This approach ensures the protection of the health and sustainability of sports facilities, contributing to the ongoing hot topics in the field., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Chromium, which can currently only be considered pharmacologically active and not an essential element, is a very intriguing elemental impurity in final pharmaceutical products, especially traditional herbal medicinal products. This kind of traditional herbal medicinal product with Marshmallow root (Althaea officinalis L., radix) registered in the EU is widely used among the European population. The aim of this article is to propose a double regulatory strategy in assessing the human health risk of total chromium impurities in cough syrups with Marshmallow Root (Althaea officinalis) available in Polish pharmacies. We applied the strategy based on the requirements of the ICH Q3D (R1) guideline for the assessment of Cr impurities in final traditional herbal medicinal products with Marshmallow Root registered in the EU. Furthermore, we applied the strategy based on the concept of margin of exposure (MoE) considering Cr(VI) genotoxicity mode of action (MOA) and based on BMD 10 for Cr(VI) as a point of departure (PoD). The total Cr content was in the range: 1.12-9.61 µg/L (in comparison with the ICH Q3D R1 guidelines: 1100 µg/g). Total Cr levels in a single dose were relatively high compared to raw results, but were not a threat to patients. Comparison of estimated results with oral PDE value for Cr in final drugs suggested by the ICH Q3D R1 guideline (10,700 µg/day) show that all the products analyzed were below this value (the highest result was 278.40 ng/day). Despite conservative assumptions, the MoE values obtained for Cr in daily dose for each Marshmallow Root cough syrup were above 10,000; therefore, exposure to Cr would not cause a health risk for specific population groups (children and adults). It can be summarized that each of the phytopharmaceuticals analysed with Marshmallow root available in Polish pharmacies does not represent a health hazard to patients. We confirm the safety of Cr impurities by applying a double regulatory strategy without the application of an expansive and demanding HPLC-ICP-MS technique for Cr speciation., (© 2024. The Author(s).)

Nerve agents (G- and V-series) are a group of extremely toxic organophosphorus chemical warfare agents that we have had the opportunity to encounter many times on a massive scale (Matsumoto City, Tokyo subway and Gulf War). The threat of using nerve agents in terrorist attacks or military operations is still present, even with establishing the Chemical Weapons Convention as the legal framework. Understanding their environmental sustainability and health risks is critical to social security. Due to the risk of contact with dangerous nerve agents and animal welfare considerations, in silico methods were used to assess hydrolysis and biodegradation safely. The environmental fate of the examined nerve agents was elucidated using QSAR models. The results indicate that the investigated compounds released into the environment hydrolyse at a different rate, from extremely fast (<1 day) to very slow (over a year); V-agents undergo slower hydrolysis compared to G-agents. V-agents turned out to be relatively challenging to biodegrade, the ultimate biodegradation time frame of which was predicted as weeks to months, while for G-agents, the overwhelming majority was classified as weeks. In silico methods for predicting various parameters are critical to preparing for the forthcoming application of nerve agents., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 The Authors. Published by Elsevier Inc. All rights reserved.)

Traditional herbal medicinal products (THMP) with Thymi herba ( Thymus vulgaris L. and Thymus zygis L.) are very popular among the European population. The idea of our study was the toxicological analysis of lead impurities in THMP with Thymi herba obtained from Polish pharmacies. For this purpose, we prepared the impurity profiles and comprehensive toxicological risk assessment. The Pb impurity profiles show lead impurities in all samples investigated (in the range: 2.15-6.99 μg/L). The estimations of Pb impurities in the single dose (32.25-105.01 ng/single dose) and in the daily dose (64.50-210.00 ng/day) were based on the posology recommended by the manufacturers. All the results obtained meet the standards of the ICH Q3D (R1) guideline on elemental impurities according to the levels of Pb. It can be concluded that all investigated THMPs with Thymi herba available in Poland should not represent any health risk to adults.

The attempt to define toxicovigilance can be based on defining its fundamental principles: prevention of infections with toxic substances, collecting information on poisonings, both in terms of their sources and side effects, and confirming poisonings, with the aim of improving treatment. Substances referred to include both those originating from animal bites, ingested inadvertently, and those resulting from environmental poisoning in industrial regions of countries, etc. In this review, we provide information about the crucial function of poison control centres in toxicovigilance, the importance of incorporating big data analytics and artificial intelligence to streamline toxicovigilance processes, and examples of toxicovigilance in different countries. In conclusion, we will present the direction that modern toxicovigilance should take, incorporating available artificial intelligence methods to maximise efficiency., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Cannabis sativa L., commonly known as industrial hemp, is a versatile plant with applications ranging from medicinal to agricultural and industrial uses. Despite its benefits, there is a notable gap in regulatory toxicology, in understanding the extent of element accumulation in hemp, which is critical due to its ability to absorb various elements from the soil, including heavy metals (Pb, Cd, Hg, and As), uptakes potential toxic elements (e.g., Sb, Sn, Sr, Bi, Tl), problematic elements (Ni, Cr, Co), and essential elements (Zn, Cu, Fe, Mn). The paper aims to enrich current understandings by offering a comprehensive analysis of elements absorption in industrial hemp. This study emphasizes the potential health risks linked with hemp consumption including regulatory toxicology aspects: limits, Permitted Daily Exposures (PDE), recommendations in different countries and from different agencies/bodies (like the WHO and the EU) based on route of administration, jurisdiction and actual literature review. This review contributes significantly to the knowledge base on hemp safety, serving as a valuable resource for researchers, regulatory bodies, and industry stakeholders., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 Elsevier Ltd. All rights reserved.)

The identification and toxicological assessment of potential carcinogens is of paramount importance for public health and safety. This study aimed to predict the carcinogenic potency and tumorigenic dose (TD 50 ) for two problematic N-nitrosamines (N-NAs) commonly found in food: N-2-methylpropyl-N-1-methylacetonylnitrosamine (NMAMPA, CAS: 93755-83-0) and N-3-Methylbutyl-N-1-methylacetonylnitrosamine (NMAMBA, CAS: 71016-15-4). To achieve this goal, in silico toxicology methods were employed due to their practical applications and potential in risk assessment. The justification for conducting these studies was incoherent results published by the European Food Safety Authority (EFSA). For this purpose, we applied various in silico tools, including qualitative methods (ToxTree, ProTox II and CarcinoPred-EL) and quantitative methods (QSAR Toolbox and LAZAR) were applied to predict the carcinogenic potency. These tools leverage computational approaches to analyze chemical structures for finding toxicophores and generating predictions, making them efficient alternatives to traditional in vivo experiments. The results obtained indicated that N-NAs are carcinogenic compounds, and quantitative data was obtained in the form of estimated doses of TD 50 for the compounds tested., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Tea is the world's most common drink after water, and the world's annual sales exceed $43 billion, of which more than $11 billion is green tea (Camellia sinensis (L.)). Increasing evidence continues to show that green tea consumption and its ingredients have a variety of potential health benefits. The aim of the study was to control and assess the toxicological risk (TRA) of three heavy metals (As, Pb, and Cd) in infusions of green tea (n = 12) from Polish markets. We applied the method of inductive coupled plasma mass spectrometry (ICP-MS) to determine the selected heavy metal and designed a specific toxicological risk assessment with three crucial tiers. The first tier of our strategy was to determine the elements investigated (heavy metal impurities, µg/L). The second step was to estimate the weekly intake of green tea infusions (µg/week) based on weekly consumption. The third tier was to estimate the weekly intake per weight (µg/L/week/bw), based on the average weekly intake of green tea infusion per adult compared to the provisional weekly intake (PTWI) established by the FAO/WHO Joint Food Additives Expert Committee (JECFA). The levels of the investigated heavy metals occur at different levels in all of the investigated green tea infusions. The heavy metal profile indicated that As (0.0721-10.585 µg/L), Pb (0.386-1.695 µg/L), and Cd (0.126-0.346 µg/L) were present in all samples. Basic analysis of general content shows that As (average = 0.325 µg/L) was at a level similar to Cd (average = 0.214 µg/L). Surprisingly, the Pb content (average 0.891 µg/L) was approximately 2.75-4 times higher than that of As and Cd, respectively. The application of our proposed safety assessment methodology (three tiers) provides satisfactory results for regulatory purposes. The evaluation of the investigated heavy metals in all products analysed from green tea samples (infusions) showed that there were no health hazards to consumers due to weekly exposure. The results indicated that after drinking green tea infusions from Polish markets, the amount of investigated elements in weekly doses does not represent any health risks to consumers., (© 2023. The Author(s).)

Nerve agents are organophosphate chemical warfare agents that exert their toxic effects by irreversibly inhibiting acetylcholinesterase, affecting the breakdown of the neurotransmitter acetylcholine in the synaptic cleft. Due to the risk of exposure to dangerous nerve agents and for animal welfare reasons, in silico methods have been used to assess acute toxicity safely. The next-generation risk assessment (NGRA) is a new approach for predicting toxicological parameters that can meet modern requirements for toxicological research. The present study explains the acute toxicity of the examined V-series nerve agents (n = 9) using QSAR models. Toxicity Estimation Software Tool (ver. 4.2.1 and ver. 5.1.2), QSAR Toolbox (ver. 4.6), and ProTox-II browser application were used to predict the median lethal dose. The Simplified Molecular Input Line Entry Specification (SMILES) was the input data source. The results indicate that the most deadly V-agents were VX and VM, followed by structural VX analogues: RVX and CVX. The least toxic turned out to be V-sub x and Substance 100A. In silico methods for predicting various parameters are crucial for filling data gaps ahead of experimental research and preparing for the upcoming use of nerve agents., (© 2023. The Author(s).)

This article focusses on the environmental implications of low-cost jewelry for adults from Chinese e-commerce platforms ((n = 8) with heavy metal impurities (Pb, Cd and Hg) and their potential impact on human health and the environment. The study highlights the advantages of using portable X-ray fluorescence (pXRF) analysis for rapid, non-destructive, and in situ analysis of heavy metals in jewelry. The results reveal that all products (n = 106) contained heavy metals at varying levels, Hg being the most commonly detected heavy metal. The fact that 71% of the samples exceeded the EU limit for Pb and 51% exceeded the EU limit for Cd is alarming and highlights the need for stricter regulations and monitoring of the jewelry industry to mitigate the risks posed by heavy metals in the environment. The study emphasizes the importance of using pXRF analysis to identify heavy metals in jewelry and address the literature gap in environmental risk assessments of Pb, Cd, and Hg in low-cost jewelry for adults from China. In general, the findings call for urgent action to ensure the safety of consumers and prevent environmental pollution by strengthening regulations and monitoring the jewelry industry., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 Elsevier B.V. All rights reserved.)

Novichoks constitute a relatively new class of nerve agents of extreme toxicity that we have had the opportunity to experience three times already. After the first case (Salisbury, UK), a public debate about Novichoks began, which resulted in the realisation of the nature of these chemicals. From a social security point of view, examining their properties, especially toxicological and environmental aspects, are crucial. After the CWC (Chemical Warfare Agent) list update, the candidate structures for the Novichoks may be over 10,000 compounds. It would be extremely laborious to conduct experimental research for each. Understanding their environmental persistence and health hazards is an essential national issue. Moreover, due to the high risk posed by contact with hazardous Novichok substances, in silico research was applied to estimate hydrolysis and biodegradation safely. The present study elucidates, using QSAR models, the environmental fate of the Novichoks studied (n = 17). The results indicate that Novichoks released into the environment hydrolyse at various rates, from extremely fast (<1 day) to very slow (more than a year). Furthermore, ultimate biodegradation from weeks to months is expected for most compounds, which classifies them as relatively difficult biodegradable. Applying reliable in silico methods (QSAR Toolbox and EPI Suite) for predicting various parameters is crucial to prepare for the upcoming usage of Novichoks., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 The Authors. Published by Elsevier B.V. All rights reserved.)

6-Thioguanine is an immunosuppressive drug, an analogue of guanine, applied to treat acute leukemia and inflammatory bowel disease. Excessive use of 6-thioguanine during clinical treatment may cause side effects. Moreover, providing a dose too low will be ineffective. Therefore, there is a critical need for a rapid, selective and routine approach to quantifying 6-thioguanine in body fluids to support a clinical application. A fully validated HPLC method has been developed to determine 6-thioguanine in whole blood samples using 5-bromouracil as an internal standard. 6-Thioguanine nucleotides were released from erythrocytes by perchloric acid, and then hydrolysed at 100 °C to the parent thiopurine, 6-thioguanine. The following validation parameters of the method were determined: specificity/selectivity, linearity range (479-17,118 ng/mL, R > 0.992), limits of detection (150 ng/mL) and quantification (479 ng/mL), accuracy (- 5.6 < Bias < 14.7), repeatability (CV 1.30-3.24%), intermediate precision (CV 4.19-5.78%), extraction recovery (79.1-103.6%) and carryover. Furthermore, the stability of the drug in whole blood samples under various storage conditions was investigated. The suggested method is suitable for determining 6-thioguanine in whole blood erythrocyte samples for drug level monitoring, thus correct dosing., (© 2023. Springer Nature Limited.)

Poisoning and overdose are very important aspects in medicine and toxicology. Chemical weapons pose a threat to civilians, and emergency medicine principles must be followed when dealing with patients who have been poisoned or overdosed. Antidotes have been used for centuries and modern research has led to the development of new antidotes that can accelerate the elimination of toxins from the body. Although some antidotes have become less relevant due to modern intensive care techniques, they can still save lives or reduce the severity of toxicity. The availability of antidotes is crucial, especially in developing countries where intensive care facilities may be limited. This article aims to provide information on specific antidotes, their recommended uses, and potential risks and new uses. In the case of poisoning, supportive therapies are most often used; however, in many cases, the administration of an appropriate antidote saves the patient's life. In this review, we reviewed the literature on selected antidotes used in the treatment of poisonings. We also characterised the antidotes (bio)chemically. We described the cases in which they are used together with the dosage recommendations. We also analysed the mechanisms of action. In addition, we described alternative methods of using a given substance as a drug, an example of which is N -acetylcysteine, which can be used in the treatment of COVID-19. This article was written as part of the implementation of the project of the Polish Ministry of Education and Science, "Toxicovigilance, poisoning prevention, and first aid in poisoning with xenobiotics of current clinical importance in Poland", grant number SKN/SP/570184/2023.

Traditional herbal medicinal products (THMP) with Plantago lanceolata L., folium (Ribwort Plantain Leaves) are well-known and very popular among the European population. The aim of our study was the toxicological risk assessment for adults of Pb impurities in THMP with Plantago lanceolata L. obtained from pharmacies in Poland. The estimations of Pb impurities in the single dose (22.1 - 50.7 ng/single dose) and in the daily dose (ng/day) were based on the worst-case scenario (WCS), i.e. based on the posology recommended by manufacturers. The estimated daily exposure (ng/day) meets the standards of the ICH Q3D (R1) guideline on elemental impurities (5.0 µg/day) according to the Pb levels (all results were below 250 ng/day). It can be concluded that all investigated THMPs with Plantago lanceolata L., folium available in pharmacies from Poland should not represent any health risk to the adults.

In conventional clinical toxicology practice, the blood level of carboxyhemoglobin is a biomarker of carbon monoxide (CO) poisoning but does not correspond to the complete clinical picture and the severity of the poisoning. Taking into account articles suggesting the relationship between oxidative stress parameters and CO poisoning, it seems reasonable to consider this topic more broadly, including experimental biochemical data (oxidative stress parameters) and patients poisoned with CO. This article aimed to critically assess oxidative-stress-related parameters as potential biomarkers to evaluate the severity of CO poisoning and their possible role in the decision to treat. The critically set parameters were antioxidative, including catalase, 2,2-diphenyl-1-picryl-hydrazyl, glutathione, thiol and carbonyl groups. Our preliminary studies involved patients ( n = 82) admitted to the Toxicology Clinical Department of the University Hospital of Jagiellonian University Medical College (Kraków, Poland) during 2015-2020. The poisoning was diagnosed based on medical history, clinical symptoms, and carboxyhemoglobin blood level. Blood samples for carboxyhemoglobin and antioxidative parameters were collected immediately after admission to the emergency department. To evaluate the severity of the poisoning, the Pach scale was applied. The final analysis included a significant decrease in catalase activity and a reduction in glutathione level in all poisoned patients based on the severity of the Pach scale: I°-III° compared to the control group. It follows from the experimental data that the poisoned patients had a significant increase in level due to thiol groups and the 2,2-diphenyl-1-picryl-hydrazyl radical, with no significant differences according to the severity of poisoning. The catalase-to-glutathione and thiol-to-glutathione ratios showed the most important differences between the poisoned patients and the control group, with a significant increase in the poisoned group. The ratios did not differentiate the severity of the poisoning. The carbonyl level was highest in the control group compared to the poisoned group but was not statistically significant. Our critical assessment shows that using oxidative-stress-related parameters to evaluate the severity of CO poisoning, the outcome, and treatment options is challenging.

Chromium is pharmacologically active and is not an essential element but is still very intriguing and demanding from the point of view of toxicological risk assessment. Especially as an elemental impurity in final pharmaceuticals. The aim of this article is toxicological risk assessment (TRA) of total Cr impurities in Menthae piperitae tinctura (Mentha x piperita L., folium) available in Polish pharmacies including triple approach. Obtained raw/basal results shows that impurities of total Cr impurities were present in all investigated pharmaceutical with Mentha x piperita L., folium. but at a relatively low level (in the range: 0.39-2.14 µg/L). The regulatory strategy based on the ICH Q3D (R1) elemental impurities guidelines confirms that all the requirements of the analyzed products meet the European Medicine Agency (EMA) requirements. Obtained results obtained show that the estimated maximum daily exposure to Cr (ng/day) are variable between the samples (0.521-3.792 ng/day), but at a relatively low level (< 4.0 ng/day).The final step confirms the safety of analyzed pharmaceuticals, because the comparison of the estimated results with the oral PDE value for Cr in final drugs suggested by the ICH Q3D guideline (10,700 µg/day) show that all the products are below this value. The approach based on the margin of exposure (MoE) for children and adults also confirms the safety of all the products with Mentha x piperita L., (in all cases MoE >  > 10 000). It can be concluded that all the samples analyzed should not represent any health hazard to patients due to Cr impurities. To our knowledge, this is the first study about application of comprehensive TRA of total Cr impurities in phytopharmaceuticals with Mentha x piperita L., folium available in European pharmacies. Additionally, we confirm the safety of Cr impurities by applying triple regulatory strategy without the application of an expansive and demanding HPLC-ICP-MS technique for Cr speciation., (© 2022. The Author(s).)

Novichoks represent the fourth generation of chemical warfare agents with paralytic and convulsive effects, produced clandestinely during the Cold War by the Soviet Union. This novel class of organophosphate compounds is characterised by severe toxicity, which, for example, we have already experienced three times (Salisbury, Amesbury, and Navalny's case) as a society. Then the public debate about the true nature of Novichoks began, realising the importance of examining the properties, especially the toxicological aspects of these compounds. The updated Chemical Warfare Agents list registers over 10,000 compounds as candidate structures for Novichoks. Consequently, conducting experimental research for each of them would be a huge challenge. Additionally, due to the enormous risk of contact with hazardous Novichoks, in silico assessments were applied to estimate their toxicity safely. In silico toxicology provides a means of identifying hazards of compounds before synthesis, helping to fill gaps and guide risk minimisation strategies. A new approach to toxicology testing first considers the prediction of toxicological parameters, eliminating unnecessary animal studies. This new generation risk assessment (NGRA) can meet the modern requirements of toxicological research. The present study explains, using QSAR models, the acute toxicity of the Novichoks studied (n = 17). The results indicate that the toxicity of Novichoks varies. The deadliest turned out to be A-232, followed by A-230 and A-234. On the other hand, the "Iranian" Novichok and C01-A038 compounds turned out to be the least toxic. Developing reliable in silico methods to predict various parameters is essential to prepare for the upcoming use of Novichoks., (© 2023. The Author(s).)

Myroxylon pereirae resin (MP; balsam of Peru) is a botanical balsam which is derived from a tree known as Myroxylon balsamum (L.) Harms var. pereirae (Royle) Harms, balsamum. This natural substance has a long history of medicinal use (antiseptic and for wound healing) but surprisingly there is a lack of toxicological data. The medicinal application of Peru balsam has been documented throughout a period of at least 30 years, however, due to the high risk of sensitisation and other treatment options available in the proposed indication, the medicinal use of MP in EU today is limited. The aim of this article is deriving Permitted Daily Exposure (PDE) values for MP for regulatory purposes using various toxicological strategies due to the problems with toxicological data. The results described in this article fills a gap in the literature on toxicological aspects of MP for the first time.

Mint tea (Mentha piperita L.) is one of the most widely consumed single infusion herbal teas (infusion) around the world; however, impurities and pollutants can pose a potential health risk to human health during tea drinking. The idea of this study was the comprehensive toxicological risk assessment (TRA) of three heavy metals (As, Pb, and Cd) in mint tea infusions (Mentha piperita L.; n = 17) available in Polish markets. We applied an inductively coupled plasma mass spectrometry (ICP-MS)-based methodology for the determination of the chosen heavy metals and designed a specific TRA approach. The first step in our TRA was the determination of the elements investigated (heavy metal impurity profile, µg/L of infusion). The second step was the estimation of the weekly intake (µg/L of infusion/week) based on the weekly consumption of tea. The third step was the estimation of the weekly intake per body weight (µg/L of infusion/week/bw) based on the weekly consumption of tea per adult person compared to the Provisional Tolerable Weekly Intake (PTWI) established by the Joint FAO/WHO Expert Committee on Food Additives (JECFA). The level of investigated heavy metals occurs in all of the investigated mint tea infusions but at a relatively low level. The heavy metal profile indicated presence of As (0.36-1.254 µg/L), Pb (0.47-1.24 µg/L), and Cd (0.17-0.40 µg/L) in all the samples investigated. The basic analysis of the general content shows that As levels (mean = 0.70 µg/L) were very similar to the Pb levels (mean = 0.72 µg/L). The Cd content (mean = 0.21 µg/L) was approximately 3.5 times lower than the As and Pb levels. TRA provides satisfactory results for regulatory purposes. TRA for the elements investigated in the analyzed products indicated that there was no health hazard to consumers for weekly exposure. The results indicated that the levels of investigated elements in daily doses should not represent any health hazard to the consumer after drinking mini tea infusions from products available in Polish markets. This well-designed TRA methodology was useful and important for regulatory toxicology purposes., (© 2022. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

All cosmetics products must be safe under foreseeable conditions of use. Allergenic responses are one of the most frequent adverse reactions noted for cosmetics. Thus, the EU cosmetics legislation requires skin sensitisation assessment for all cosmetics ingredients, including the regulated ones (for which the full toxicological dossier needs to be analysed by the Scientific Committee on Consumer Safety (SCCS)) and those (perceived as less toxic) which are assessed by industrial safety assessors. Regardless of who performs the risk assessment, it should be carried out using scientifically and regulatory body-accepted methods. In the EU, reference methods for chemical toxicity testing are defined in the relevant Annexes (VII-X) of the Registration, Evaluation, Authorisation and Restriction of Chemicals (REACH) Regulation. Recommendations for Skin Sensitization (Skin Sens) testing are provided in Annex VII, and this particular endpoint information is required for all EU-registered chemicals. Historically, in vivo animal and human methods have been used. Both raise ethical doubts, and some of them cause practical problems in the objective analysis of skin sensitising potency. Previous decades of huge effort have resulted in the regulatory acceptance of the alternative Skin Sens IATA (Integrated Approaches to Testing and Assessment) and NGRA (Next Generation Risk Assessment). Regardless of the testing issues, a serious sociological problem are observed within the market: the consumer assumes the presence of strong sensitisers in cosmetics formulations and insufficient risk management tools used by the industry. The present review aims to provide an overview of methods for assessing skin sensitisation. Additionally, it aims to answer the following question: what are the most potent skin sensitisers used in cosmetics? The answer considers the mechanistic background along with the actual regulatory status of ingredients and practical examples of responsible industry solutions in the area of risk management.

Our study's objective is to evaluate the potential health effects of elemental impurities (Ag, Au, Co, Cr, Cs, Li, Mo, Se, and Sr) found in green tea infusions ( Camellia sinensis (L.)). The ICP-MS-based methodology was employed for elemental analysis and a detailed health risk evaluation based on weekly consumption (μg/L of infusion/week). The provisional tolerable weekly intake (PTWI), established by the Joint FAO Expert Committee on infusion/week/month based on existing literature data, was then compared to the subjects with data from the available literature. The exposure of the study items to Co ranged from 0.07904 to 0.85421 μg/day. On the contrary, the ICH (International Council for Harmonisation of Technical Requirements for Pharmaceuticals for Human Use) guidelines state that the established permitted daily exposure PDE (oral exposure) for Co is 50 μg/day. The PDE of lithium is around 560 μg/day, and according to our study, the estimated daily exposure of the evaluated products to Li fell between 0.0185 and 0.7170 μg/day. Our research also revealed modest concentrations of Cs (0.399-2.654 μg/L), Mo (0.0113-0.107 μg/L), and Sr (9.848-22.331 μg/L) in infusions. The recognized PDE for molybdenum is approximately 3400 μg/day. Only two samples contained silver, and when considering daily consumption, the predicted daily exposure to Ag is between 4.4994 and 0.03122 μg/day. The amounts of all evaluated elements in a daily dose of green tea infusions should not harm the consumer's health. Further considerations should take aspects, such as constant change and environmental pollution, into account.

Novichoks-organophosphorus compounds belong to the nerve agents group, constituting the fourth generation of chemical warfare agents. The tremendous toxicity of Novichoks is assumed to be several times greater than that of VX, whereas no published experimental research supports this. They were surreptitiously created during the Cold War by the Soviet Union. Novichok's toxic action mechanism consists of the inhibition of acetylcholinesterase activity. The review includes data on treating poisoning caused by OPs which could be used as guidelines for the therapy in case of Novichok exposure and HAZMAT/CBRNE approaches. Novichoks pose a severe threat due to their toxicity; however, there is insufficient information about the identity of A-series nerve agents. Filling in the missing data gaps will accelerate progress in improving protection against Novichoks and developing optimal therapy for treating poisoning casualties. Furthermore, introducing solutions to protect medical personnel in contact with a hazardous substance increases the chances of saving casualties of HAZMAT/CBRNE incidents.

In recent years, research on silver nanoparticles (AgNPs) has attracted considerable interest among scientists because of, among other things, their alternative application to well-known medical agents with antibacterial properties. The size of the silver nanoparticles ranges from 1 to 100 nm. In this paper, we review the progress of research on AgNPs with respect to the synthesis, applications, and toxicological safety of AgNPs, and the issue of in vivo and in vitro research on silver nanoparticles. AgNPs' synthesis methods include physical, chemical, and biological routes, as well as "green synthesis". The content of this article covers issues related to the disadvantages of physical and chemical methods, which are expensive and can also have toxicity. This review pays special attention to AgNP biosafety concerns, such as potential toxicity to cells, tissues, and organs.

Traditional herbal medicinal products (THMP) with Thymi herba are very popular as OTC among the European population. The aim of this article was the toxicological risk assessment (TRA) of Cd impurities in THMP with Thymi herba from Polish pharmacies. The estimations of Cd impurities in the single dose (1.10-12.90 µg/single dose) and in the daily dose (ng/day) were based on the worst-case scenario (WC), i.e. based on the dosage indicated in the community herbal monograph on Thymus vulgaris L. and Thymus zygis L., herba by the European Medicines Agency (EMA). The estimated daily exposure (ng/day) meets the standards of the ICH Q3D (R1) guideline (5.0 µg/day) according to the Cd levels (all results were below 40 ng/day). It can be concluded that all THMPs analysed with Thymi herba from Polish pharmacies should not represent any health risk to the human health.

Novichok is the name given to the group of nerve agents created stealthily in the later phases of the Cold War by the Soviet Union. Constitute the fourth generation of chemical warfare agents; like other nerve agents, they are organophosphorus compounds designed to be incurable and undetectable. The mechanism of action is based on the non-competitive and irreversible inhibition of acetylcholinesterase. Due to their enormous toxicity, Novichoks have become attractive targets for terrorists. However, little information is known about the identity of nerve agents. Furthermore, these compounds have never been submitted to the Chemical Weapons Convention. Our article aspires to provide a general overview of Novichoks knowledge. As part of this, we reviewed the available literature data to answer the question, what are Novichoks? In addition to the physical and chemical properties of A-agents, synthesis, mechanism of action, and toxicity of nerve agents were also reviewed. We hope that this review will highlight the tremendous threat posed by nerve agents and will inspire further studies on the interdisciplinary aspects of these compounds., (© 2022. The Author(s).)

The scoping review aimed to characterise the role of selected essential elements (Zn, Cu, Se, Fe, Mn) in food for special medical purposes (FSMPs) aimed at oncology patients. The scope review was conducted using Scopus, Google Scholar, and Web of Science to find published references on this subject. Data from the reviewed literature were related to the physiological functions of the element in the body, and the effects of deficiencies and excesses, referring to the latest ESPEN and EFSA guidelines, among others. Important dietary indices/parameters based on the literature review are provided for each element. On the basis of the literature, data on the level of elements in patients with cancer were collected. The content of these elements in 100 mL of FSMPs was read from the manufacturers' declarations. The literature has been provided on the importance of each element in cancer. Our findings show that the essential elements (Zn, Cu, Se, Fe, and Mn) of FSMPs for cancer patients are not adequately treated. We suggest solutions to ensure the safe use of FSMPs in oncology patients.

Potential heavy metal impurities (HMI) in pharmaceuticals/pharmaceutical products/drugs based on plant raw materials (e.g., herbs) are an important problem in the pharmaceutical industry; however, there is a lack of scientific articles on the comprehensive toxicological risk assessment of HMI in ointment applied dermally. To make the appropriate toxicological risk assessment, we consider: (1) the raw results of the levels of lead and cadmium in the ointments (metal per kg of mass), (2) one-time administration of the applied ointment, (3) daily exposure of Pb and Cd in the applied ointments according to the maximum daily dose of applied pharmaceuticals, including transcutaneous penetration, (4) human health risk assessment based on the USEPA model, and 5) the margin of exposure (MoE). The raw results indicated that lead (7.05-101.78 µg/kg) and cadmium (0.32-0.81 µg/kg) were present in all samples. The levels of analyzed HMI (independently of the producer and declared composition) were similar. Pb and Cd contamination associated with daily doses met the standards of the ICH Q3D (R2) guide on elemental impurities in pharmaceuticals, including the cutaneous route of administration. Taking into account the daily amount of lead and cadmium (ointment, ug/day) the results were satisfactory, confirming the safety of marjoram herb extract ointments available in Polish pharmacies according to the ICH guideline Q3D (R2) on elemental impurities. The HQ values obtained for Pb and Cd in all samples were less than 1; therefore, exposure to these HMI would not cause a health risk based on the USEPA model strategy. Furthermore, the obtained values of MoE for Pb and Cd in ointments were above 100, so exposure to these elements would not cause a health risk based on the MoE-based strategy. The original contribution of this work is that this is the first study on the triple approach strategy to evaluate the safety of heavy metal impurities in traditional herbal medicinal products applied dermally in solid form (ointments with marjoram herb extract). The research is novel and has not been previously published; The proposed procedure includes transcutaneous penetration of heavy metal (Pb and Cd) impurities described for the first time in the literature.

The purpose of our studies is the evaluation of the health risks of the novel elemental impurities (Ag, Au, Co, Cs, Li, Mo, Se, Sr, and V) in mint tea infusions ( Mentha piperita L.) available in Poland. For this purpose, we applied ICP-MS-based methodology for content analysis (elemental profile and µg/L of the infusion) and also the specific health risk assessment for a comprehensive assessment. Our strategy was based on weekly intake (µg/L of infusion/week) considering weekly tea consumption. Then, based on the weekly consumption of tea per adult, individuals were compared to the Temporary Tolerated Weekly Intake (PTWI) designated by the Joint FAO Expert Committee on Food Additives (JECFA), and the weekly consumption per body weight (µg/L of infusion/week/bw) was estimated. Daily exposure to Co in the tested products is in a range of 0.093-0.238 µg/day. In comparison, the established PDE (oral exposure) for Co by the ICH guideline (the ICH guideline Q3D (R1), 2019) is 50 µg/day. For lithium, PDE is approximately 560 µg/day and, in our study, the estimated daily exposure for Li in investigated products is in a range of 0.226-2.41 µg/day. Our studies found also low levels of Cs (in a range of 0.0598-0.195 µg/L), Mo (in a range of 0.663-3.261 µg/L), and Sr (0.223-65.842 µg/L) in infusions. For Molybdenum, the established PDE is approximately 3400 µg/day. There are no documents about Sr and Co in the Joint FAO/WHO Expert Committee on Food Additives (JECFA) database and the ICH guideline Q3D (R1). In the case of V, the established PDE is 120 µg/day, and the level of V in analyzed infusions is in a range of 0.284-0.702 µg/L. Silver and gold were present only in a few samples, and the estimated daily exposure for Ag is approximately 0.04575 µg/day for product A and approximately 0.1885 µg/day for product O, except for Au, which is in a range of 0.000356-0.114 µg/L. The estimated daily exposure for Ag is 167 µg/day and, for Au, it is in a range of 8.9 × 10 5 -0.0285 µg/day. It can be concluded that levels of all investigated elements (novel and also traditional elemental impurities) in the daily dose should not threaten the consumer's health after consuming mint tea infusions.

In this article, we have presented the development and validation of a rapid and sensitive reversed-phase liquid chromatography with tandem mass spectrometry (LC-MS/MS) method for the determination of vincristine (VCR) in patient serum samples. Chromatographic separation was achieved on a Kinetex® (Singapore) column using a mobile phase consisting of 25 mM acetic acid and 0.3% formic acid (A) and methanol (B) in a gradient elution mode at a flow rate of 0.3 mL/min. The VCR and internal standard (vinblastine) were monitored using the multiple reaction monitoring mode under positive electrospray ionization. The lower limit of quantification (LLOQ) was 0.67 ng/mL, and the upper limit of quantification (ULOQ) was 250 ng/mL for VCR. The calculated values of LOD and LOQ for VCR were 0.075 and 0.228 ng/mL, respectively. The calibration curve was linear over the VCR concentration range of 1.0−250 ng/mL in serum. The intra- and inter-day precision and precision were within the generally accepted criteria for the bioanalytical method (<15%). The method was successfully applied to the analysis of serum samples in clinical practice.