Toxicological Methods Research Articles

Modern alternative research methods in genetic toxicology (literature review)

The review represents the current principles of assessment of chemicals genotoxicity. The main attention is paid to alternative research methods. The international experience of the application of alternative approaches and prospects of their use for regulatory purposes are discussed. The data for this review were collected from the Russian and foreign literature, as well as Internet resources, concerning the development of the new alternative methods for testing chemicals for genotoxicity. The OECD database, Scopus, Medline, Google Scholar, RISC, CyberLeninka were used for the information retrieval. Although the evaluation of genotoxicity of chemical substances is the well-established and based on the battery of validated methods, the studies for improving the existing tests and developing new technologies, including the alternative approaches, continue unabated up to now. In general, three trends of development of genetic toxicology can be outlined, including creating of new methods based on the whole-genome sequencing and the application of genome editing technologies; implementation of quantitative system of effects assessment in addition to the existing qualitative approach (mutagenic/non-mutagenic) and testing of various combinations of genotoxicity evaluation methods to identify a battery of tests with a greater predictive activity regarding carcinogenic effects. To use the developed alternative models for regulatory purposes, it is necessary to provide convincing evidence that the data obtained are good predictors of the organism’s actual response to the effects of toxicants/genotoxicants, validation of methods, standardization, and harmonization of research protocols, and changes to the existing regulatory framework are required.

Investigating the relationship of co-exposure to multiple metals with chronic kidney disease: An integrated perspective from epidemiology and adverse outcome pathways

Systematic studies on the associations between co-exposure to multiple metals and chronic kidney disease (CKD), as well as the underlying mechanisms, remain insufficient. This study aimed to provide a comprehensive perspective on the risk of CKD induced by multiple metal co-exposures through the integration of occupational epidemiology and adverse outcome pathway (AOP). The study participants included 401 male mine workers whose blood metal, β2-microglobulin (β2-MG), and cystatin C (Cys-C) levels were measured. Generalized linear models (GLMs), quantile g-computation models (qgcomp), least absolute shrinkage and selection operator (LASSO), and bayesian kernel machine regression (BKMR) were utilized to identify critical nephrotoxic metals. The mean concentrations of lead, cadmium, mercury, arsenic, and manganese were 191.93, 3.92, 4.66, 3.11, 11.35, and 16.33 µg/L, respectively. GLM, LASSO, qgcomp, and BKMR models consistently identified lead, cadmium, mercury, and arsenic as the primary contributors to kidney toxicity. Based on our epidemiological analysis, we used a computational toxicology method to construct a chemical-genetic-phenotype-disease network (CGPDN) from the Comparative Toxicogenomics Database (CTD), DisGeNET, and GeneCard databases, and further linked key events (KEs) related to kidney toxicity from the AOP-Wiki and PubMed databases. Finally, an AOP framework of multiple metals was constructed by integrating the common molecular initiating events (reactive oxygen species) and KEs (MAPK signaling pathway, oxidative stress, mitochondrial dysfunction, DNA damage, inflammation, hypertension, cell death, and kidney toxicity). This is the first AOP network to elucidate the internal association between multiple metal co-exposures and CKD, providing a crucial basis for the risk assessment of multiple metal co-exposures.

Toxicity of Bromo-DragonFLY as a New Psychoactive Substance: Application of In Silico Methods for the Prediction of Key Toxicological Parameters Important to Clinical and Forensic Toxicology.

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 (LD50), 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.

Contaminant levels versus toxicity bioassays in ecological risk assessment of sediments from the southern Baltic Sea

Surface sediments collected in 2021 from six locations in the southern Baltic Sea (Polish district) were examined by chemical and toxicological methods. Chemical analyses included polybrominated diphenyl ethers (PBDEs), polycyclic aromatic hydrocarbons (PAHs), and their alkylated derivatives, butyltin compounds and 16 major and trace elements. The toxicity was measured using Ostracodtoxkit F and Microtox. The ecological risk of sediment was estimated by hazard quotient (HQ) calculation. Some PAHs, alkylated PAHs and metals (Zn, Hg, Cd and As) could pose a moderate risk in the sediments from the Gdańsk Deep and in the vicinity of the wrecks, but the risk resulting from the presence of all analyzed compounds was considered high for these sediments. In studies using biotests, sediments from the vicinity of the t/s Franken wreck and the Słupsk Furrow were highly toxic to test organisms. Ostracodtoxkit F, compared to Microtox, appeared a more sensitive test for measured compounds.

Assessment of Δ9-THC and Δ9-THCCOOH bias, precision, and ionization suppression/enhancement between solid tissue homogenate and supernatant by LC-MS-MS.

Liquid chromatography-triple quadrupole mass spectrometry (LC-MS-MS) assays are frequently utilized for screening and confirmatory purposes in the forensic toxicology laboratory. While these techniques are excellent for the targeted identification and quantitation of a wide variety of drug classes, validation and determining fit-for-purpose is a significant requirement for each method. In the USA, the American National Standards Institute and Academy Standards Board first edition of Standard 036 currently serves as a primary resource in forensic toxicology method validation and mandates that laboratories evaluate critical performance characteristics to help ensure the production of forensically defensible results. Due to the variability of specimen quality frequently encountered in the discipline of postmortem toxicology, the State of Maryland Office of the Chief Medical Examiner Forensic Toxicology Laboratory routinely analyzes solid tissue specimens as part of the medicolegal death investigation process and evaluates liver as a representative solid tissue matrix during method validation. Authentic postmortem specimens (e.g. liver, kidney, skeletal muscle, and spleen) were used to investigate the effects of analyzing solid tissue homogenate versus solid tissue supernatant on bias, precision, and ionization suppression/enhancement of Δ9-THC and Δ9-THCCOOH. Bias was <20% for Δ9-THC and Δ9-THCCOOH in liver homogenate and supernatant with a single exception of the low QC concentration for Δ9-THC in liver homogenate (-29%). Within-run and between-run CV was <20% for Δ9-THC and Δ9-THCCOOH in liver homogenate and supernatant. Δ9-THC and Δ9-THC-d3 exhibited significant ion suppression in both liver homogenate and supernatant, while Δ9-THCCOOH and Δ9-THCCOOH-d3 showed both ion suppression and enhancement in these matrices. Noticeable quantitative differences were observed in authentic postmortem solid tissue homogenate and supernatant specimens despite evaluating identical tissue samplings. A brief discussion of the results is presented using a validated LC-MS-MS method for the confirmation and quantitation of Δ9-THC and Δ9-THCCOOH in postmortem casework.

Elucidating the degradation mechanisms of perfluorooctanoic acid and perfluorooctane sulfonate in various environmental matrices: a review of green degradation pathways.

Given environmental persistence, potential for bioaccumulation, and toxicity of Perfluorooctanoic acid (PFOA) and perfluorooctane sulfonate (PFOS), the scientific community has increasingly focused on researching their toxicology and degradation methods. This paper presents a survey of recent research advances in the toxicological effects and degradation methods of PFOA and PFOS. Their adverse effects on the liver, nervous system, male reproductive system, genetics, and development are detailed. Additionally, the degradation techniques of PFOA and PFOS, including photochemical, photocatalytic, and electrochemical methods, are analyzed and compared, highlighted the potential of these technologies for environmental remediation. The biotransformation pathways and mechanisms of PFOA and PFOS involving microorganisms, plants, and enzymes are also presented. As the primary green degradation pathway for PFOA and PFOS, Biodegradation uses specific microorganisms, plants or enzymes to remove PFOA and PFOS from the environment through redox reactions, enzyme catalysis and other pathways. Currently, there has been a paucity of research conducted on the biodegradation of PFOA and PFOS. However, this degradation technology is promising owing to its specificity, cost-effectiveness, and ease of implementation. Furthermore, novel materials/methods for PFOA and PFOS degradation are presented in this paper. These novel materials/methods effectively improve the degradation efficiency of PFOA and PFOS and provide new ideas and tools for the degradation of PFOA and PFOS. This information can assist researchers in identifying flaws and gaps in the field, which can facilitate the formulation of innovative research ideas.

The investigation of the toxicity of organophosphorus flame retardants (OPFRs) by using in silico toxicity prediction platform ProTox- 3.0

From the past to the present, many chemicals have been used for the purpose of flame retardant. Due to PBDEs’ (Polybrominated diphenyl ether) lipophilic and accumulative properties, some of them are banned from the market. As an alternative to these chemicals, OPFRs (organophosphorus flame retardants) have started to be used as flame retardants. In this article, acute toxicity profiles, mutagenicity, carcinogenicity, blood-brain barrier permeability, ecotoxicity and nutritional toxicity as also AHR, ER affinity and MMP, aromatase affinity, CYP2C9, CYP3A4 interaction of the of 16 different compounds of the OPFRs were investigated using a computational toxicology method; ProTox- 3.0. According to our results, eight compounds were found to be active in terms of carcinogenic effect, whereas two compounds were found to be active for mutagenicity. On the other hand, all compounds were found to be active in terms of blood-barrier permeability. Fourteen compounds and four compounds are found to have ecotoxic and nutritional toxic potency, respectively. Eight compounds were determined as active to AhR, and four chemicals were found to be active in Estrogen Receptor alpha. Eight chemicals were found to be active in terms of mitochondrial membrane potency. Lastly, three chemicals were found to be active in aromatase enzymes. In terms of CYP interaction potencies, eight compounds were found to be active in both CYP2C9 and CYP3A4. This research provided novel insights into the potential toxic effects of OPFRs. However, further studies are needed to evaluate their toxicity. Moreover, these findings lay the groundwork for in vitro and in vivo toxicity research.

Knowledge infrastructure for integrated data management and analysis supporting new approach methods in predictive toxicology and risk assessment

The EU-ToxRisk project (2016–2021) was a large European project working towards shifting toxicological testing away from animal tests, towards a toxicological assessment based on comprehensive mechanistic understanding of cause-consequence relationships of chemical adverse effects. More than 40 partners from scientific institutions, industry and regulators coordinated their work towards this goal in a six-year long programme. The breadth and variety of data and knowledge generated, presented a challenging data management landscape.Here, we describe our approach to data management as developed under EU-ToxRisk. The main building blocks of the data infrastructure are: 1) An easy-to-use, extensible data and metadata format; 2) A flexible system with protocols for data capture and sharing from the entire consortium; 3) A methods database for describing and reviewing data generation and processing protocols; 4) Data archiving using a sustainable resource; 5) Data transformation from the archive to the system that provides granular access; 6) Application Programming Interface (API) for access to individual data points; 7) Data exploration and analysis modules, based on a «web notebook» approach to executable data processing documentation; and 8) Knowledge portal that ties together all of the above and provides a collaboration space for information exchange across the consortium. This knowledge infrastructure is being extended and refined for the support of follow-up projects (RISK-HUNT3R, ASPIS cluster, European Open Science Cloud (2021–2026)).

A review of Aconiti Lateralis Radix Praeparata (Fuzi) for kidney disease: phytochemistry, toxicology, herbal processing, and pharmacology.

Aconiti Lateralis Radix Praeparata, commonly known as Fuzi in. traditional Chinese medicine (TCM), is widely utilized in clinical practice despite its inherent toxicity. Since ancient times, TCM practitioners have explored various processing techniques to broaden its clinical applications and enhance its safety profile. This review aims to summarize the effects of processing on the chemical composition, toxicity, and pharmacological properties of Fuzi, as well as investigate potential underlying mechanisms. Data on phytochemistry, toxicology, pharmacology, and processing methods of Fuzi were gathered from the literature of electronic databases, including Web of Science, PubMed, and CNKI. Fuzi contains over 100 kinds of chemical compounds, including alkaloids, flavonoids, and polysaccharides, among which alkaloids are the main active compounds. Diester-diterpenoid alkaloids are the main contributors to Fuzi's toxicity and have side effects on some organs, such as the heart, liver, kidneys, nervous system, and reproductive system. The chemical composition of aconite, particularly its alkaloid content, was changed by hydrolysis or substitution reaction during processing to enhance its efficacy and reduce its toxicity. Salted aconite could enhance the therapeutic efficacy of Fuzi in treating kidney diseases and influence its pharmacokinetics. Processing plays an important role in increasing the efficiency and decreasing toxicity of aconite. Further studies are needed to elucidate the changes of aconite before and after processing and the underlying mechanisms of these changes, thereby providing evidence for the clinical safety of drug use.

Effectiveness and Perception of Collaborative Learning among Undergraduates Students: Introduction of Jigsaw Method in Forensic Toxicology

Background: Didactic teaching being teacher centric usually does not generate sense of responsibility for learning among the students. The Jigsaw method is a form of cooperative learning that improves not only the cognitive but also the affective and psychomotor skills, which are required by a student to become an Indian Medical Graduate. Thus, this study was aimed at assessing the effectiveness of Jigsaw strategy in comparison to didactic teaching and to understand the perception of the students. Methodology: This was a quasi-experimental study conducted among second year MBBS students. They were randomly assigned to lecture and Jigsaw groups. A topic on general toxicology was chosen. Handouts were prepared which were given to all the students. The lecture group was taught using audio visual aids. The topic was sub divided into five subtopics for Jigsaw group. A post test consisting of MCQs was used to assess the effectiveness of the method. A validated questionnaire was used to gather feedback from the students belonging to Jigsaw Group. Descriptive statistics were used to analyze responses to the Likert scale questions. Results: The present study included a total of 65 II year MBBS students, out of which 30 students were in Jigsaw group. A total of 94% students agreed to participate actively in the Jigsaw session. Most of the students (93%) students listened to and respected the ideas of their peers. A total of 72% students found this method of learning useful in Forensic Medicine and Toxicology. Only 53% of the students felt that the time for preparation and presentation of the topic was sufficient. Conclusions: The present study advocates this cooperating learning method to be an effective tool in better understanding of the subject, to improve communication skills and to inculcate lifelong learning attitude among the medical graduates. The jigsaw method, however, requires more time for planning and execution, to yield positive outcomes.

Innovative approaches to cardiovascular safety pharmacology assessment

This editorial prefaces the annual themed issue on safety pharmacology (SP) methods which has been published since 2004 in the Journal of Pharmacological and Toxicological Methods (JPTM). Here we highlight content derived from the 2023 Safety Pharmacology Society (SPS) meeting held in Brussels, Belgium. The meeting generated 138 abstracts, reproduced in the current volume of JPTM. As in prior years, the manuscripts reflect various areas of innovation in SP including in silico modeling of stroke volume, cardiac output and systemic vascular resistance, computational approaches that compare drug-induced proarrhythmic sensitivity of human-induced pluripotent stem cell-derived cardiomyocytes (hiPSC-CMs), an evaluation of the utility of the corrected J-Tpeak and Tpeak-to-Tend parameters from the ECG as potential proarrhythmia biomarkers, and the applicability of nonclinical concentration-QTc (C-QTc) modeling of data derived from the conduct of the in vivo QTc study as a component of the core battery of safety pharmacology studies.

Simultaneous multi-targeted forensic toxicological screening in biological matrices by MRM-IDA-EPI mode

The toxicologist ascertains drug assumptions in case of paediatric intoxications and death for overdose. The analytical approach consists of initially screening and consequently confirming drug positivity. We developed a toxicological screening method and validated its use comparing the results with a LC–MS/MS analysis. The method identifies 751 drugs and metabolites (704 in positive and 47 in negative mode). Chromatographic separation was achieved eluting mobile phase A (10 mM ammonium formate) and B (0.05% formic acid in methanol) in gradient on Kinetex Phenyl-Hexyl (50 × 4.6 mm, 2.6 μm) with 0.7 mL/min flow rate for 11 min. Multiple Reaction Monitoring (MRM) was adopted as survey scan and, after an Information-Dependent Analysis (IDA) (threshold of 30,000 for positive and 1000 cps for negative mode), the Enhanced Product Ion (scan range: 50–700 amu) was triggered. The MS/MS spectrum generated was compared with one of the libraries for identification. Data processing was optimised through creation of rules. Sample preparation, mainly consisting of deproteinization and enzymatic hydrolysis, was set up for different matrices (blood, urine, vitreous humor, synovial fluid, cadaveric tissues and larvae). Cut-off for most analytes resulted in the lowest concentration tested. When the results from the screening and LC–MS/MS analysis were compared, an optimal percentage of agreement (100%) was assessed for all matrices. Method applicability was evaluated on real paediatric intoxications and forensic cases. In conclusion, we proposed a multi-targeted, fast, sensitive and specific MRM-IDA-EPI screening having an extensive use in different toxicological fields.

Research Progress on Detection of New Psychoactive Substance Piperazines in vivo.

Piperazines are a class of new psychoactive substances with hallucinogenic effects that affect the central nervous system by affecting the level of monoamine neurotransmitters. Abuse of piperazines will produce stimulating and hallucinogenic effects, accompanied by headache, dizziness, anxiety, insomnia, vomiting, chest pain, tachycardia, hypertension and other adverse reactions, and may even cause cardiovascular diseases and multiple organ failure and lead to death, seriously affecting human physical and mental health and public safety. The abuse of new psychoactive substance piperazines has attracted extensive attention from the international community. The study of its pharmacological toxicology and analytical methods has become a research hotspot in the field of forensic medicine. This paper reviews the in vivo processes, sample treatment and analytical methods of existing piperazines, in order to provide reference for forensic identification.

Lung surfactant inhibition and cytotoxicity at the air-liquid interface of dry particle aerosols

Industrial processes generate chemicals that have the potential to be aerosolized and inhaled by workers, thereby posing health risks. Traditional toxicology methods employing animal models cannot keep up with the pace of emerging hazards. Nascent in vitro practices face challenges regarding translatability to the real world. To address this critical gap, this study demonstrated a workflow utilizing aerosol characterization in a more realistic exposure scenario: dry powder aerosolization onto the air-liquid interface of lung cells. This study delves into biophysical aspects of lung function by examining lung surfactant inhibition. A set of particulates, including aluminum, aluminum oxide, carbon nanotubes, diesel particulate matter, and colloidal silica, was selected for investigation. Particles were in the respirable regime, with mean aerodynamic diameters ranging from 111 to 162 nm by number and 369–2884 nm by mass. Carbon nanotubes and colloidal silica were identified as surfactant inhibitors. Aerosol doses reduced cell viability, up to 38%, with the most pronounced effects observed in response to exposure to aluminum and diesel particulate matter. Dry particle exposure at the air-liquid interface shows promise even at low doses, compared with nebulization or inoculation to submerged cultures. Our findings underscore the potential of this innovative approach for assessing the hazards of aerosolized particulates and emerging contaminants, offering a more accurate representation of real-world exposure scenarios.

Combining chemical analysis and toxicological methods to access the ecological risk of complex contamination in Daye Lake

As one of the nine primary non-ferrous metal smelting bases in China, Daye Lake basin was polluted due to diverse human activities. But so far the pollution status and related ecological risks of this region have not been detailly investigated. In current study, pollutants including heavy metals, polycyclic aromatic hydrocarbons (PAHs) and organochlorine pesticides (OCPs) in eight sediment samples from Daye Lake were quantified. 18S rRNA gene sequencing was employed to profile the nematode community structure within these sediments. Model organism Caenorhabditis elegans (C. elegans) were further applied for a comprehensive ecological risk assessment of Daye Lake. Notably, Cadmium (Cd) was identified as a key driver of ecological risk, reaching an index of 1287.35. At sample point S4, OCPs particularly p,p′-DDT, displayed an extreme ecological risk with a value of 23.19. Cephalobidae and Mononchida showed strong sensitivity to pollutant levels, reinforcing their suitability as robust bioindicators. The composite pollutants in sampled sediments caused oxidative stress in C. elegans, with gene Vit-2 and Mtl-1 as sensitive biomarkers. By employing the multiple analysis methods, our data can offer valuable contributions to environmental monitoring and health risk assessment for composite polluted areas.

Application of Green Toxicology in Personal Care Products

This research paper discusses green toxicology. Toxic substances are everywhere in our daily lives. Toxicology is usually applied in public health because all the drugs used for humans’ health are made of chemicals. With the application of toxicology, people can acknowledge the adverse effects of the drugs on people’s health. Then, people could develop safer drugs for people’s health—a little different from toxicology, green toxicology concerns both health and environmental impact. Green toxicology is a type of toxicology that applies toxicology to sustainable development and production in society. It uses toxicity testing in earlier stages of the production cycle to be time and cost-efficient. When green toxicology is applied to drug production, the production process would think about how to produce safer products with fewer adverse effects on people and the environment. As green toxicology relates to the impacts of toxins on the environment and people, the effects of contaminants on people’s health should be explored. Every material that people use is made up of harmful or beneficial chemical substances. Because much of the information about the chemicals has not been revealed until now, many products that people use, such as personal care products, might consist of toxic substances. Personal care products should be composed of safe products because many of those contact people's bodies and skin. Utilizing green toxicological methods in the production of personal care products is crucial. By examining the chemicals used and the production cycles, the possible solution by application of green toxicology will be stated.

Safety and quality of different domestic manufacturers and determination of its falsification

At the current stage, the dairy industry in Ukraine is at a fairly high level, although in comparison with world standards, it does not meet the world level in a number of indicators. One of the main tasks for Ukraine as a member of the WTO and in connection with the prospect of its accession to the EU is the harmonization of national regulatory and legal requirements with international ones in the field of food safety and quality. The purpose of the study is to evaluate the safety and quality of sour cream obtained from various domestic manufacturers, as well as to determine its adulteration according to generally accepted methods and developed patented express methods. Analytical, organoleptic, physico-chemical, microbiological, toxicological and statistical methods of research were used to implement the research goal. Sour cream produced by Ukrainian dairy enterprises according to organoleptic indicators (appearance, color, consistency, smell, taste) and physicochemical indicators (mass fraction of fat, titrated acidity, phosphatase, temperature during storage) met the requirements of the current national standard of Ukraine - DSTU 4418:2005. With the exception of sour cream of samples No. 1 and No. 5) - the fat content is reduced, and respectively 8.72±0.07% and 9.10±0.95% (according to the standards of 15−40%) and increased titrated acidity (sample No. 1) − 109.0±1.43 °T (according to standards of 60–100 °T). According to the microbiological tests of sour cream, the content of viable lactic acid bacteria was significantly lower - from (1.16±0.21)x102 to (1.42±0.21)x103 CFU/g compared to the normative indicators (1.0x107 CFU/g), which indicated a significant reduction in the contamination of the product by microorganisms as a result of compliance with sanitary and hygienic requirements for sour cream production. The content of coliform bacteria, Salmonella bacteria, Listeria monocytogenes bacteria, Staphylococcus aureus bacteria, yeast, mold fungi in sour cream met the regulatory requirements of the current national standard of Ukraine - DSTU 4418:2005. During the determination of product falsification, the presence of impurities of starch, sodium hydrogen carbonate, alkaline detergents, hydrogen peroxide, gelatin, and vegetable fats in the sour cream of the producers (samples No. 1 and No. 5) was found; no impurities were detected in the sour cream of other producers. The content of toxic elements (heavy metals), mycotoxins, antibiotics and hormonal drugs in sour cream did not exceed the maximum permissible level (MRL). Express and optimized methods for determining adulteration of sour cream have been developed. Key words: dairy industry, food product, sour cream, organoleptic, physicochemical, microbiological, toxicological indicators, safety, quality, consumer.

Aspartame carcinogenic potential revealed through network toxicology and molecular docking insights

The research employed network toxicology and molecular docking techniques to systematically examine the potential carcinogenic effects and mechanisms of aspartame (l-α-aspartyl-l-phenylalanine methyl ester). Aspartame, a commonly used synthetic sweetener, is widely applied in foods and beverages globally. In recent years, its safety issues, particularly the potential carcinogenic risk, have garnered widespread attention. The study first constructed an interaction network map of aspartame with gastric cancer targets using network toxicology methods and identified key targets and pathways. Preliminary validation was conducted through microarray data analysis and survival analysis, and molecular docking techniques were employed to further examine the binding affinity and modes of action of aspartame with key proteins. The findings suggest that aspartame has the potential to impact various cancer-related proteins, potentially raising the likelihood of cellular carcinogenesis by interfering with biomolecular function. Furthermore, the study found that the action patterns and pathways of aspartame-related targets are like the mechanisms of known carcinogenic pathways, further supporting the scientific hypothesis of its potential carcinogenicity. However, given the complexity of the in vivo environment, we also emphasize the necessity of validating these molecular-level findings in actual biological systems. The study introduces a fresh scientific method for evaluating the safety of food enhancers and provides a theoretical foundation for shaping public health regulations.

Risk meters and markers of accelerated aging

The purpose of the study is to analyze scientific research on the establishment of risk meters and markers of aging, in order to take a set of measures to prevent accelerated aging and the development of occupational diseases in the working population, including using models on laboratory animals. Material and methods: analytical, toxicological, hygienic and statistical research methods. The object of the study was the results of our own original research on the influence of environmental factors (vibration, noise, 4-component mixture of hydrocarbons) on the organisms of model animals, as well as published research material on the establishment of risk meters and markers of aging. The results and their discussion. The study determined a direct relationship between gender, age and duration of exposure to environmental factors on model organisms exposed to 90-day exposure to occupational hazards, which made it possible to establish risk meters and markers of premature aging in animals of experimental groups, compared with the control group. The results obtained experimentally will contribute to the adoption of measures to protect the health of the labor contingent. Conclusion. The leading role of timely adoption of a set of health-saving measures to prevent the development of occupational diseases in the labor contingent is determined, based on established risk meters and markers of accelerated aging using organisms of model animals.

The correlation between chemical ingredients and acute toxicity of Psoraleae Fructus and two classic prescriptions

Objective: To compare the acute toxicity and chemical ingredients of Psoraleae Fructus (PF) with those of two classic prescriptions, Ershen Wan (ESW) and Sishen Wan (SSW). Methods: Based on classical toxicological methods, body weight, food and water consumption, lethal conditions, and toxic reactions were recorded after administering single oral doses of PF, ESW, and SSW. The 50% lethal dose (LD50) values of PF and ESW and the maximum tolerance dose (MTD) of SSW were determined. In addition, PF, ESW, and SSW constituents were detected using ultra-high-performance liquid chromatography/mass spectrometry (UPLC-MS), and the spectrum-toxicity correlation was analyzed. Results: The LD50 of PF and ESW were 53.9 g/kg/day (46.2–63.0 g/kg/day, 95% confidence limit [CL]) and 68.3 g/kg/day (59.0–78.9 g/kg/day, 95% CL), which were respectively about 40 and 50 times the human daily dosage. The MTD of SSW was 41.0 g/kg/day, indicating the highest safety. What can be inferred from the chemical ingredients and toxicity correlation analyses is that compatibility reduced the contents of 13 potential hepatotoxin compounds in PF. Conclusions: The classic compatibility of ESW and SSW effectively attenuated the hepatotoxicity of PF, which was related to the reduced content of potentially toxic substances, particularly coumarins. This study explored the principles of attenuating the toxicity of classic prescriptions to provide a reference for the rational clinical use of PF.