Toxicological Methods Research Articles

ВЛИЯНИЕ НЕКОТОРЫХ ЗАГРЯЗНЯЮЩИХ ВЕЩЕСТВ НА НЕКТОБЕНТИЧЕСКИХ РАКООБРАЗНЫХ

Background. Ingress of pollutants in water bodies, both direct and from the catchment area, is constantly increasing. It creates an escalating threat to aquatic ecosystems and humans as consumers of water and aquatic biological resources, which contributes to the relevance of the monitoring and regulation of water pollution. This work is aimed at the evaluation of the effect of various toxic substances and pollutants on the survival of the amphipod Hyalella azteca in a chronic experiment. Methods. This study has been carried out according to the standard toxicological methods. Results. This paper presents the data on the influence of pollutants of various nature (sodium hydrogen phosphate, sodium sulfate, zinc complex of 2-Phosphono-1,2,4-butanetricarboxylic acid, dimethyl sulfide) on the Hyalella azteca Saussure, 1858 crustaceans. Hyalella azteca have found a wide application in biotesting; however, these crustaceans are not used in the system of fisheries regulation in Russia. The maximum allowable and threshold concentrations of the investigated substances in the aquatic environment have been established for Hyalella azteca using the experimental approach. The maximum allowable concentration (MAC) of sodium hydrogen phosphate in the phosphorus equivalent was 1.0 mg/L, its threshold concentration was 2.5 mg/L; the MAC of sodium sulfate in the sulfate anion equivalent was 750 mg/L, its threshold concentration was more than 750 mg/L; the MAC of the zinc complex of 2-Phosphono-1, 2,4-butanetricarboxylic acid was 10 mg/L, its threshold concentration was 100 mg/L; the MAC of dimethyl sulfide was 10 mg/L, its threshold concentration was 20 mg/L. Conclusion. The amphipods H. azteca are moderately sensitive to pollutants. Among all investigated substances, the most toxic for H. azteca was sodium hydrogen phosphate.

Efficient analysis of adverse drug events and toxicological mechanisms of newly marketed drugs by integrating pharmacovigilance and network toxicology: selumetinib as an example.

To integrate pharmacovigilance and network toxicology methods to explore the potential adverse drug events (ADEs) and toxic mechanisms of selumetinib, and to provide a reference for quickly understanding the safety and toxicological mechanisms of newly marketed drugs. Taking selumetinib as an example, this study integrated pharmacovigilance methods based on real-world data and network toxicology methods to analyze its ADE and its potential toxicological mechanism. First, the ADE reports of selumetinib were extracted from the US Food and Drug Administration (FDA) adverse event reporting system (FAERS), and the ADE signals were detected by reporting odds ratio (ROR) and UK medicines and healthcare products regulatory agency (MHRA) methods. The ADE signals were classified and described according to the preferred terms (PTs) and system organ class (SOC) derived from the Medical Dictionary for Regulatory Activities (MedDRA). The network toxicology method was used to analyze the toxicological mechanism of the interested SOCs. The specific steps included predicting the potential targets of selumetinib using TOXRIC, STITCH, ChEMBL, CTD, SwissTargetPreditcion, and Super-PRED databases, collecting the targets of SOC using GeneCards database, conducting protein-protein interaction (PPI) analysis through STRING database, conducting gene ontology (GO) and Kyoto encyclopedia of genes and genomes (KEGG) analysis through DAVID database, and testing the molecular affinity using AutoDock software. A total of 1388 ADE reports related to selumetinib were extracted, and 53 positive signals were detected by ROR and MHRA methods, of which 20 signals were not mentioned in the package insert, including ingrowing nail, hyperphosphatemia, cardiac valve disease, hematuria, neutropenia, etc. Analysis of the toxicological mechanism of six SOCs involved in positive ADE signals revealed that the key targets included EGFR, STAT3, AKT1, IL6, BCL2, etc., and the key pathways included PI3K/Akt pathway, apoptosis, ErbB signaling pathway, and EGFR tyrosine kinase inhibitor resistance, etc. Molecular docking assays showed spontaneous binding of selumetinib to key targets in these pathways. The pharmacovigilance analysis identified some new potential ADEs of selumetinib, and the network toxicology analysis showed that the toxic effects of selumetinib may be related to PI3K/Akt pathway, apoptosis, ErbB signaling pathway, EGFR tyrosine kinase inhibitor resistance and other pathways.

Applying new approach methodologies to assess next-generation tobacco and nicotine products.

In vitro toxicology research has accelerated with the use of in silico, computational approaches and human in vitro tissue systems, facilitating major improvements evaluating the safety and health risks of novel consumer products. Innovation in molecular and cellular biology has shifted testing paradigms, with less reliance on low-throughput animal data and greater use of medium- and high-throughput in vitro cellular screening approaches. These new approach methodologies (NAMs) are being implemented in other industry sectors for chemical testing, screening candidate drugs and prototype consumer products, driven by the need for reliable, human-relevant approaches. Routine toxicological methods are largely unchanged since development over 50 years ago, using high-doses and often employing in vivo testing. Several disadvantages are encountered conducting or extrapolating data from animal studies due to differences in metabolism or exposure. The last decade saw considerable advancement in the development of in vitro tools and capabilities, and the challenges of the next decade will be integrating these platforms into applied product testing and acceptance by regulatory bodies. Governmental and validation agencies have launched and applied frameworks and "roadmaps" to support agile validation and acceptance of NAMs. Next-generation tobacco and nicotine products (NGPs) have the potential to offer reduced risks to smokers compared to cigarettes. These include heated tobacco products (HTPs) that heat but do not burn tobacco; vapor products also termed electronic nicotine delivery systems (ENDS), that heat an e-liquid to produce an inhalable aerosol; oral smokeless tobacco products (e.g., Swedish-style snus) and tobacco-free oral nicotine pouches. With the increased availability of NGPs and the requirement of scientific studies to support regulatory approval, NAMs approaches can supplement the assessment of NGPs. This review explores how NAMs can be applied to assess NGPs, highlighting key considerations, including the use of appropriate in vitro model systems, deploying screening approaches for hazard identification, and the importance of test article characterization. The importance and opportunity for fit-for-purpose testing and method standardization are discussed, highlighting the value of industry and cross-industry collaborations. Supporting the development of methods that are accepted by regulatory bodies could lead to the implementation of NAMs for tobacco and nicotine NGP testing.

The validation of regulatory test methods - Conceptual, ethical, and philosophical foundations.

Validation establishes the reproducibility and relevance of regulatory test methods, particularly for new approach methods (NAMs) as alternatives to animal testing. While validation concepts provide a framework to assess method suitability, they rarely undergo method-critical assessment. This paper explores the philosophical and ethical foundations of the validation process, drawing from various philosophical traditions and contemporary ethical frameworks. How validation intersects with utilitarian principles, ethics of responsibility, and post-modern critiques is examined, offering a multifaceted perspective on its role in scientific progress and societal values. The paper argues for a paradigm shift in validation, moving beyond traditional animal-based comparisons towards more flexible, fit-for-purpose approaches that embrace emerging technologies and ethical con-siderations. Key ethical principles guiding NAM validation are discussed, including beneficence, non-maleficence, justice, and respect for animal welfare. Integrating these principles with scientific rigor can create a more holistic validation framework that balances human safety, animal welfare, and technological innovation. By critically examining the philosophical underpinnings of validation, this paper aims to stimulate dialogue on reforming the process to better align with contemporary scientific knowledge, ethical standards, and societal expectations. It calls for a more adaptive, transparent, and ethically grounded approach to validation that can accelerate the adoption of innovative and human-relevant toxicological methods while maintaining scientific integrity and public trust.

C60 fullerene nanoparticles permeability through the model lipid envelope of coronavirus and their anticoronavirus effect in the in ovo system

Background: An urgent problem of modern biomedicine is the search for potential ways to reduce the spread of coronavirus infections in human and animal populations and eliminate the impact of coronavirus on their bodies. Aim of the work was to determine the structural organization of C60 fullerenes in a model cell medium, to assess their potential ability to penetrate the model lipid envelope of a coronavirus, thus destroying its integrity, as well as the effectiveness of the anticoronavirus action in the in ovo system. Methods: The research was conducted using the Gromacs 2020 software package and the Charmm36 force field. The CHARMM-GUI web resource was used to construct the lipid envelope of a coronavirus. Virological and toxicological methods were used in the in ovo experiments. Results: It is shown that at the initial stages of molecular dynamics C60 fullerene forms small nanoclusters in the amount of 7–16 molecules, which is affected by the initial concentration of C60 fullerene in a model cell medium. At the same time, the shape of nanostructures for the number of molecules over 16 may differ from the correct spherical shape. It was established that C60 fullerene and its nanoclusters are able to penetrate inside the lipid envelope of a coronavirus. In particular, a single C60 molecule can migrate, completely embed itself in the lipid envelope, or move within it. It was found that C60 fullerene aqueous solution, at the maximum permissible concentration (MPC) of 30 μg/embryo, reduces the infectious activity of the chicken infectious bronchitis (CIB) coronavirus when it is used 1, 2 and 4 h after the infection of a sensitive biological system with a coronavirus. Conclusions: It is shown that aggregation of C60 fullerene in a model cell medium can occur in different ways: either before penetration into the lipid envelope of a coronavirus, or inside it. C60 fullerenes, both individually and as part of nanoclusters, are able to form pores in the envelope of a coronavirus, destroying its integrity, which possibly leads to disruption of the corresponding stages of its replication cycle and attachment to cell receptors. It was established that C60 fullerene aqueous solution, when used in the MPC value, shows antiviral activity against the CIB coronavirus in its early stages of interaction with the cell (1–4 h).

Ethylene oxide: methodological approaches to the determination of residues in food products (literature review)

Introduction. Ethylene oxide is a prohibited fumigant in the Russian Federation and the states of the European Union (EU), however, the substance is used in a number of other countries to disinfect food before they are sold, so there is a risk of such products entering the Russian market, which can lead to negative consequences for public health. The residues of the fumigant in consumed products can cause neurological disorders and the development of cancer in humans. In addition, the presence of 2-chloroethanol in foodstuffs, the main transformation product of ethylene oxide, which is formed during the interaction of the fumigant with the matrix, is of concern. 
 Material and methods. The analysis of domestic and foreign databases and regulatory legal acts on the regulation of the dangers of ethylene oxide and 2-chloroethanol was carried out.
 Results. The toxicological characterization of ethylene oxide and 2-chloroethanol shows the need to establish acceptable levels of contaminants in food, and, as a result, to create a simple and effective analytical control method. 
 Limitations.The study is limited to a review of open literature sources in describing the toxicological characterization and methods of analysis of ethylene oxide in food products.
 Conclusion. The analysis of open literature sources has shown the need for scientific substantiation of hygienic standards and the development of a method for controlling the content of ethylene oxide and 2-chloroethanol in food products.

Maternal exposure to E 551 during pregnancy leads to genome-wide DNA methylation changes and metabolic disorders in the livers of pregnant mice and their fetuses

The widespread use of nanoparticles in the food industry has raised concerns regarding their potential adverse effects on human health, particularly in vulnerable populations, including pregnant mothers and fetuses. However, studies evaluating the reproductive and developmental toxicity of food-grade nanomaterials are limited. This study investigated the potential risks of prenatal dietary exposure to food-grade silica nanoparticles (E 551) on maternal health and fetal growth using conventional toxicological and epigenetic methods. The results showed that prenatal exposure to a high-dose of E 551 induces fetal resorption. Moreover, E 551 significantly accumulates in maternal and fetal livers, triggering a hepatic inflammatory response. At the epigenetic level, global DNA methylation is markedly altered in the maternal and fetal livers. Genome-wide DNA methylation sequencing revealed affected mCG, mCHG, and mCHH methylation landscapes. Subsequent bioinformatic analysis of the differentially methylated genes suggests that E 551 poses a risk of inducing metabolic disorders in maternal and fetal livers. This is further evidenced by impaired glucose tolerance in pregnant mice and altered expression of key metabolism-related genes and proteins in maternal and fetal livers. Collectively, the results of this study highlighted the importance of epigenetics in characterizing the potential toxicity of maternal exposure to food-grade nanomaterials during pregnancy.

Optimizing Sex Ratios of Hyalella azteca to Reduce Variability in Reproduction and Improve Reproductive Toxicity Test Methods.

Standard toxicological test methods with Hyalella azteca incorporate both lethal and sublethal (growth, reproduction) endpoints, although lethal endpoints are often favored in routine testing. However, sublethal endpoints are important to consider because they are ecologically relevant and are often more sensitive than lethality. It is difficult to achieve robust data for reproduction in H. azteca because high biological variability is associated with reproductive yield, likely due to complex interactions in mate selection, which can add to the variability in brood sizes that females produce. In addition, effects on reproduction often co-occur with effects on growth, making it difficult to differentiate effects on growth from those on reproduction in standard tests initiated with juveniles. The present study characterized the reproductive capacity of H. azteca by investigating the role of sex ratios in reproductive yield. Experiments were initiated in the absence of toxicants with sexually mature (6-8-week-old) individuals that were placed in different female-to-male ratios (1:1, 2:3, 3:2, and 7:3). Reproduction was monitored during weekly static renewals for 7 weeks. The results indicated that a higher female:male ratio (seven females to three males) improved reproductive success and lowered biological variability in reproduction. In addition, the body lengths and weights of newly mature amphipods were used to create a size distribution to aid in the identification of small female amphipods. Based on the results of our study, a novel reproductive toxicity test method is proposed that begins with sexually mature amphipods in a ratio of seven females to three males to minimize reproductive variability in amphipods and to enable a more effective assessment of contaminants using reproduction as a highly sensitive endpoint. However, evaluation of this novel method with toxicants is needed to demonstrate that results are comparable to standard methods.Environ Toxicol Chem 2024;43:712-722. © 2023 The Authors. Environmental Toxicology and Chemistry published by Wiley Periodicals LLC on behalf of SETAC.

Genotoxicity Evaluation of Titanium Dioxide Nanoparticles In Vivo and In Vitro: A Meta-Analysis.

Recent studies have raised concerns about genotoxic effects associated with titanium dioxide nanoparticles (TiO2 NPs), which are commonly used. This meta-analysis aims to investigate the potential genotoxicity of TiO2 NPs and explore influencing factors. This study systematically searched Chinese and English literature. The literature underwent quality evaluation, including reliability evaluation using the toxicological data reliability assessment method and relevance evaluation using routine evaluation forms. Meta-analysis and subgroup analyses were performed using R software, with the standardized mean difference (SMD) as the combined effect value. A total of 26 studies met the inclusion criteria and passed the quality assessment. Meta-analysis results indicated that the SMD for each genotoxic endpoint was greater than 0. This finding implies a significant association between TiO2 NP treatment and DNA damage and chromosome damage both in vivo and in vitro and gene mutation in vitro. Subgroup analysis revealed that short-term exposure to TiO2 NPs increased DNA damage. Rats and cancer cells exhibited heightened susceptibility to DNA damage triggered by TiO2 NPs (p < 0.05). TiO2 NPs could induce genotoxicity, including DNA damage, chromosomal damage, and in vitro gene mutations. The mechanism of DNA damage response plays a key role in the genotoxicity induced by TiO2 NPs.

Decolonizing Veterinary History: On the benefits of telling the story of Dr Jotello Soga, the first South African veterinarian

Although nearly erased from history, the first formally trained South African veterinarian was the little-known Dr Jotello Festiri Soga (1865–1906), son of the Xhosa Reverend Tiyo Soga and his Scottish wife. By detailing Soga's remarkable trajectory, this paper helps to decolonize the history of veterinary medicine, long dominated by the ‘great deeds’ of a succession of white men, and only recently beginning to diversify. This sort of knowledge decolonization has been increasingly advocated by numerous scholars and a growing number of students globally. Dr Soga qualified as a Member of the Royal College of Veterinary Surgeons in 1886, after studying at the Royal (Dick's) Veterinary School in Edinburgh. Appointed Assistant Veterinary Surgeon for Cape Colony in 1889, he made pioneering contributions to veterinary toxicology and vaccination methods over the next decade. Soga was also one of the earliest to warn of the impending disaster of rinderpest, and he played an instrumental role in the containment and eventual eradication of this devastating disease. He provided essential help in communicating with indigenous South Africans about livestock diseases, although his feelings about his countrymen were sometimes conflicted. The processes of decolonization are complex, and frequently difficult, but the benefits are great.

Lactobacillus (Limosilactobacillus) reuteri: a probiotic candidate to reduce neonatal diarrhea in calves.

Diarrhea in newborn calves is considered life-threatening and results in large economic losses in dairy farms. Lactobacilli generally play an important role in intestinal health, and Lactobacillus (Limosilactobacillus; L.) reuteri is the dominant Lactobacillus species in the feces of healthy calves during the first week of life. In calves with diarrhea on day 2 postpartum, lactobacilli are significantly reduced even up to 24 h before the onset of clinical signs. Since the probability of occurrence of diarrheal disease decreases as the L. reuteri count in the feces increases, oral administration of this species might have a protective effect against diarrhea. These studies were designed to demonstrate whether oral administration of preselected L. reuteri isolates can reduce the incidence of diarrhea in newborn calves on dairy farms. 46 L. reuteri isolates from 2-day-old healthy calves were available from a previous study. 170 newborn calves of Simmental breed of 10 dairy farms in Bavaria (Germany), were included in the study; of 166 animals the data could be evaluated. Microbiological (antibiotic sensitivity test, acid and bile salt stability test, antimicrobial activity of the supernatants), molecular biological (PCR, RAPD-PCR) and toxicological methods (MTT test) were used to select and to characterize suitable L. reuteri isolates. The administration of a suspension of two selected L. reuteri isolates (6-8 × 108 colony forming units per day) to calves was performed from day 2 to day 5 after birth in a double-blinded placebo-controlled study. Clinical monitoring of the calves continued until the 14th day of life. Out of 46 L. reuteri isolates, only 2 met the set criteria and were used in the feeding trial. In the placebo group, 44 of 83 calves developed diarrhea within the first 2 weeks of life, whereas in the L. reuteri group this was only the case in 31 of 83 animals (p < 0.05). L. reuteri appears to be of particular importance for the intestinal health of newborn calves. The diarrhea protective effect could be even more pronounced if an improved administration regimen is developed in terms of start, frequency, and duration.

Comparison of female rat reproductive effects of pubertal versus adult exposure to known endocrine disruptors.

A prevailing challenge when testing chemicals for their potential to cause female reproductive toxicity is the lack of appropriate toxicological test methods. We hypothesized that starting a 28-day in vivo toxicity study already at weaning, instead of in adulthood, would increase the sensitivity to detect endocrine disruptors due to the possibility of including assessment of pubertal onset. We compared the sensitivity of two rat studies using pubertal or adult exposure. We exposed the rats to two well-known human endocrine disruptors, the estrogen diethylstilbestrol (DES; 0.003, 0.012, 0.048 mg/kg bw/day) and the steroid synthesis inhibitor ketoconazole (KTZ; 3, 12, 48 mg/kg bw/day). Specifically, we addressed the impact on established endocrine-sensitive endpoints including day of vaginal opening (VO), estrous cyclicity, weights of reproductive organs and ovarian histology. After 28 days of exposure, starting either at weaning or at 9 weeks of age, DES exposure altered estrous cyclicity, reduced ovary weight as well as number of antral follicles and corpora lutea. By starting exposure at weaning, we could detect advanced day of VO in DES-exposed animals despite a lower body weight. Some endpoints were affected mainly with adult exposure, as DES increased liver weights in adulthood only. For KTZ, no effects were seen on time of VO, but adrenal and liver weights were increased in both exposure scenarios, and adult KTZ exposure also stimulated ovarian follicle growth. At first glance, this would indicate that a pubertal exposure scenario would be preferrable as timing of VO may serve as sensitive indicator of endocrine disruption by estrogenic mode of action. However, a higher sensitivity for other endocrine targets may be seen starting exposure in adulthood. Overall, starting a 28-day study at weaning with inclusion of VO assessment would mainly be recommended for substances showing estrogenic potential e.g., in vitro, whereas for other substances an adult exposure scenario may be recommended.

Removal of heavy metals using sorbents and biochemical indexes in rats

A wide range of negative effects of heavy metals on the body of mammals predetermined the relevance of the search for ways to reduce the toxic effects of these chemical compounds. Solving this problem is possible by using sorbents. The research aims to determine the effect of sorbents on the content of heavy metals (cadmium, copper, lead, and zinc) in the rat tissues. Toxicological, physicochemical, and biochemical methods were used. Phillipsite sorbent reduced the content of copper and zinc in the blood of rats by 1.6 times, cadmium by 2 times and lead by 2.6 times. The content of copper and zinc in rat livers decreased by 1.4 times, and cadmium and lead – by 2 times. The content of the studied metals in kidney tissues decreased by half. A similar decrease in the level in the tissues was noted when using the chabazite sorbent for all heavy metals studied. Administration of the clinoptilolite sorbent into the body of rats contributed to a 2-fold decrease in the blood content of copper and zinc, cadmium, and lead by 2.6 and 3 times, respectively. A 1.6-fold decrease in copper and zinc levels and a 3-fold decrease in cadmium and lead levels were detected in the liver tissues. When mordenite sorbent was administered to animals, the content of copper and zinc in the blood decreased by 1.5 times, and cadmium and lead by 3 times compared to the control. The content of all studied metals in the liver of rats decreased by 2.4 times. The use of these sorbents in animal husbandry will contribute to the reduction of the content of heavy metals in animal tissues, which will ensure the production of high-quality and safe products, as well as contribute to the preservation of human health

Integrating Mechanistic and Toxicokinetic Information in Predictive Models of Cholestasis.

Drug development involves the thorough assessment of the candidate's safety and efficacy. In silico toxicology (IST) methods can contribute to the assessment, complementing in vitro and in vivo experimental methods, since they have many advantages in terms of cost and time. Also, they are less demanding concerning the requirements of product and experimental animals. One of these methods, Quantitative Structure-Activity Relationships (QSAR), has been proven successful in predicting simple toxicity end points but has more difficulties in predicting end points involving more complex phenomena. We hypothesize that QSAR models can produce better predictions of these end points by combining multiple QSAR models describing simpler biological phenomena and incorporating pharmacokinetic (PK) information, using quantitative in vitro to in vivo extrapolation (QIVIVE) models. In this study, we applied our methodology to the prediction of cholestasis and compared it with direct QSAR models. Our results show a clear increase in sensitivity. The predictive quality of the models was further assessed to mimic realistic conditions where the query compounds show low similarity with the training series. Again, our methodology shows clear advantages over direct QSAR models in these situations. We conclude that the proposed methodology could improve existing methodologies and could be suitable for being applied to other toxicity end points.

Safety pharmacology 2023 and implementation of the ICH E14/S7B Q&A guidance document

This editorial prefaces the annual themed issue on safety pharmacology (SP) methods published since 2004 in the Journal of Pharmacological and Toxicological Methods (JPTM). We highlight here the content derived from the recent 2022 Safety Pharmacology Society (SPS) and Canadian Society of Pharmacology and Therapeutics (CSPT) joint meeting held in Montreal, Quebec, Canada. The meeting also generated 179 abstracts (reproduced in the current volume of JPTM). As in previous years the manuscripts reflect various areas of innovation in SP including a comparison of the sensitivity of cross-over and parallel study designs for QTc assessment, use of human-induced pluripotent stem cell (hi-PSC) neuronal cell preparations for use in neuropharmacological safety screening, and hiPSC derived cardiac myocytes in assessing inotropic adversity. With respect to the latter, we anticipate the emergence of a large data set of positive and negative controls that will test whether the imperative to miniaturize, humanize and create a high throughput process is offset by any loss of precision and accuracy.

Green analytical toxicology method for determination of synthetic cathinones in oral fluid samples by microextraction by packed sorbent and liquid chromatography-tandem mass spectrometry.

We developed and validated a method for quantitative analysis of ten synthetic cathinones in oral fluid (OF) samples, using microextraction by packed sorbent (MEPS) for sample preparation followed by liquid chromatography‒tandem mass spectrometry (LC‒MS/MS). OF samples were collected with a Quantisal™ device and 200 µL was extracted using a C18 MEPS cartridge installed on a semi-automated pipette and then analyzed using LC‒M/SMS. Linearity was achieved between 0.1 and 25ng/mL, with a limit of detection (LOD) of 0.05ng/mL and a limit of quantification (LOQ) of 0.1ng/mL. Imprecision (% relative standard deviation) and bias (%) were better than 11.6% and 7.5%, respectively. The method had good specificity and selectivity against 9 different blank OF samples (from different donors) and 68 pharmaceutical and drugs of abuse with concentrations varying between 400 and 10,000ng/mL. No evidence of carryover was observed. The analytes were stable after three freeze/thaw cycles and when kept in the autosampler (10°C) for up to 24h. The method was successfully applied to quantify 41 authentic positive samples. Methylone (mean 0.6ng/mL, median 0.2ng/mL), N-ethylpentylone (mean 16.7ng/mL, median 0.35ng/mL), eutylone (mean 39.1ng/mL, median 3.6ng/mL), mephedrone (mean 0.5ng/mL, median 0.5ng/mL), and 4-chloroethcathinone (8.1ng/mL) were quantified in these samples. MEPS was an efficient technique for Green Analytical Toxicology purposes, which required only 650 µL organic solvent and 200 µL sodium hydroxide, and the BIN cartridge had a lifespan of 100 sample extractions.

Simultaneous determination of water-soluble herbicides using hydrophilic interaction liquid chromatography-mass spectrometry.

The analysis of water-soluble herbicides, including glyphosate (Glyp), glufosinate (Gluf), paraquat (PQ), and diquat (DQ), is time-consuming and expensive because they cannot be analyzed using general toxicological screening methods. Thus, this study aimed to develop a simple and rapid method to simultaneously analyze these compounds without any derivatization nor ion-pairing reagents. The analytes were separated using hydrophilic interaction liquid chromatography and detected using tandem mass spectrometry. The developed method was applied to plant and biological samples assuming criminal damage and poisoning cases, respectively. All analytes were separated well and detected with good peak shapes. For plant samples, the herbicides were specifically detected from withered leaves using a simple extraction method. For biological samples, quantitative analysis was successfully validated, and the limit of quantification values of Glyp and Gluf were 0.2µg/mL, and those of PQ and DQ were 1ng/mL. The developed method had sufficient performance for practical forensic applications including poisoning cases and malicious uses to damage commercial crops.

Recent Advances in Drug Discovery Toxicology.

Major advances in scientific discovery and insights that stem from the development and use of new techniques and models can bring remarkable progress to conventional toxicology. Although animal testing is still considered as the "gold standard" in traditional toxicity testing, there is a necessity for shift from animal testing to alternative methods regarding the drug safety testing owing to the emerging state-of-art techniques and the proposal of 3Rs (replace, reduce, and refine) towards animal welfare. This review describes some recent research methods in drug discovery toxicology, including in vitro cell and organ-on-a-chip, imaging systems, model organisms (C. elegans, Danio rerio, and Drosophila melanogaster), and toxicogenomics in modern toxicology testing.

Luminescence Toxicological Analysis of Water Supply Systems in Dispersed Rural Areas: A Case Study in Boyacá, Colombia

The quality of water supply systems is still a major problem in developing countries, especially in rural areas. The acute bioluminescence V. fischeri inhibition assay is widely recognized as a toxicological method that can be used to detect the acute effects of different contaminants. In this study, the physicochemical characteristics and toxicology of 72 water samples collected in 18 rural aqueducts located in Boyacá (Colombia) were evaluated. The primary economic activities identified as potential influencers of water quality in the water supply basins were agriculture (n = 3), livestock (n = 2), and domestic sewage discharge (n = 1). The average luminescence inhibition rate was 66%, with a minimum of 29%, and a maximum of 97%. A total of 85% of the tested samples (n = 61) had “moderate acute hazard”, while 15% (n = 15) had “acute hazard”. A total of 95% of the aqueducts distributed water with high risk. There was a weak positive correlation between the apparent color and the V. fischeri inhibition rate (p &lt; 0.05). The water treatments, including disinfection, and the economic activities had no correlation with the inhibition rate of luminescent bacteria. The results of this investigation can be used by sanitary authorities to incorporate future toxicological monitoring of chemical contaminants, such as humic substances and metals, into water-quality monitoring in rural areas.

Integrating Computational Data Science in University Curriculum for the New Generation of Scientists

Integration of computational data science (CDS) into the university curriculum offers several advantages for students, faculty and the institution. This article discusses the benefits to students of introducing CDS into the university curriculum with a focus on developing skills in cheminformatics, data analysis, structure–activity relationships, modelling and simulation. Moreover, CDS can enable students to engage with complex chemical and toxicological data in new and dynamic ways, helping them to develop a more nuanced understanding of the potential hazards and risks associated with different chemicals and substances. On the other hand, it can foster greater collaboration between students and faculty and with external partners in industry and government. This can lead to the development of more effective and efficient toxicological testing methods and tools to screen chemicals for potential hazards and aid the development of environmentally friendly chemicals. Overall, the integration of CDS into the university curriculum will help prepare the next generation of scientists giving them a competitive edge to make considerable contributions to green chemistry, designing safer chemicals and non-animal testing methods. It will enable them to tackle modern challenges facing society including identifying safer and more sustainable chemicals and predicting the health and environmental impacts of novel chemical substances.