Toxicity Tests Research Articles

LP-35 Use of high-content screening technology for toxicological testing

LP-35 Use of high-content screening technology for toxicological testing

Deciphering mechanisms of UV filter (benzophenone-3)- and high temperature-induced adverse effects in the coral Acropora tenuis, using ecotoxicogenomics

Coral reefs are at risk of bleaching due to various environmental and anthropogenic stressors such as global warming and chemical pollutants. However, there is little understanding of stressor-specific mechanisms that cause coral bleaching. Therefore, conducting accurate ecotoxicological risk assessments and deciphering modes of action of potentially deleterious ultraviolet (UV) filters (sunscreen compounds) are crucial issues. In this study, we evaluated the toxicity and bleaching effect of benzophenone-3 (BP-3), which is widely used in sunscreen products, on the reef-building coral Acropora tenuis. Furthermore, to understand differences in UV filter- and temperature-induced adverse effects, a comparative ecotoxicogenomic approach using RNA-seq was integrated into a toxicity test to clarify differences in gene expression changes induced by BP-3 and heat stress (31 °C). The lethal concentration 50 % (LC50) was calculated as 3.9 mg/L, indicating that the aquatic environmental risk on corals posed by BP-3 was low based on the risk assessment in this study. Differentially expressed genes related to oxidative stress and extracellular matrix organization were involved in coral responses to both BP-3 and heat stress, but their patterns differed. Whereas immune and heat-shock responses were activated in response to heat stress, activation of a drug metabolism pathway and several signal transduction pathways were identified in BP-3 treatment groups. Our study enhances understanding of stress responses in corals induced by UV filters and thermal stress. Using potential gene markers identified in this study for eco-epidemiological surveys of stressed corals, we urgently need to develop effective countermeasures.

LP-29 Development of human pluripotent stem cell-derived liver organoids for liver toxicity testing

LP-29 Development of human pluripotent stem cell-derived liver organoids for liver toxicity testing

Non-conventional endpoints show higher sulfoxaflor toxicity to Chironomus riparius than conventional endpoints in a multistress environment

Evidence grows that standard toxicity testing might underestimate the environmental risk of neurotoxic insecticides. Behavioural endpoints such as locomotion and mobility have been suggested as sensitive and ecologically relevant additions to the standard tested endpoints. Possible interactive effects of chemicals and additional stressors are typically overlooked in standardised testing. Therefore, we aimed to investigate how concurrent exposure to environmental stressors (increased temperature and predation cues) and a nicotinic acetylcholine receptor (nAChR)-modulating insecticide (‘sulfoxaflor’) impact Chironomus riparius across a range of conventional and non-conventional endpoints. We used a multifactorial experimental design encompassing three stressors, sulfoxaflor (2.0–110 µg/L), predation risk (presence/absence of predatory cues), and elevated temperature (20 °C and 23 °C), yielding a total of 24 distinct treatment conditions. Additional stressors did not change the sensitivity of C. riparius to sulfoxaflor. To assess potential additive effects, we applied an Independent Action (IA) model to predict the impact on eight endpoints, including conventional endpoints (growth, survival, total emergence, and emergence time) and less conventional endpoints (the size of the adults, swimming abilities and exploration behaviour). For the conventional endpoints, observed effects were either lower than expected or well-predicted by the IA model. In contrast, we found greater than predicted effects of predation cues and temperature in combination with sulfoxaflor on adult size, larval exploration, and swimming behaviour. However, in contrast to the non-conventional endpoints, no conventional endpoints detected interactive effects of the neurotoxic insecticide and the environmental stressors. Acknowledging these interactions, increasing ecological context of ecotoxicological test systems may, therefore, advance environmental risk analysis and interpretation as the safe environmental concentrations of neurotoxic insecticides depend on the context of both the test organism and its environment.

P20-27 Zinc suphide – considerations and challenges for acute inhalation toxicity testing and classification under REACH

P20-27 Zinc suphide – considerations and challenges for acute inhalation toxicity testing and classification under REACH

P14-02 Contractility-based pharmacological characterization of hiPSC-derived atrial and ventricular cardiomyocytes for preclinical toxicity testing

P14-02 Contractility-based pharmacological characterization of hiPSC-derived atrial and ventricular cardiomyocytes for preclinical toxicity testing

Synthesis, Spectral Analysis, Antimicrobial Evaluation, Molecular Modelling, DFT, TD‐DFT and SAR Studies of Novel 4,5,6,7‐Tetrabromo‐1H‐benzo[d][1,2,3]triazole Derivatives

AbstractThis study evaluated 14 new 4,5,6,7‐tetrabromo‐1H‐benzo[d][1,2,3]triazole derivatives (3a‐n) for their antimicrobial activities, identifying compound 3k as the most effective. In vivo oral toxicity tests confirmed its non‐toxic nature. Predictive ADME analysis indicated favorable drug development properties. Molecular docking and dynamics studies were performed to investigate the interactions of compound 3k with Mycobacterium TB (PDB ID 2X22) and glucosamine‐6‐phosphate synthase (PDB ID 2VF5). The reactivity properties and reactive sites were determined using DFT‐derived HOMO and LUMO orbitals, along with MEP, and ESP maps, providing insights into the electron density, electrophilicity, and nucleophilicity. The electronic properties of the TD‐DFT and IEFPCM models were analyzed in solvents such as acetonitrile, ethanol, and DMSO and results were compared using UV‐Vis spectroscopy. Structural–activity relationship (SAR) investigations elucidated biological activities.

P05-16 Prioritising plant protection products for toxicity testing by in silico screening

P05-16 Prioritising plant protection products for toxicity testing by in silico screening

P01-65 In vitro developmental toxicity testing based on real-time monitoring for signal disruption

P01-65 In vitro developmental toxicity testing based on real-time monitoring for signal disruption

P21-71 Expanding fish invitrome-based methods as alternatives to animal use in aquatic toxicity testing

P21-71 Expanding fish invitrome-based methods as alternatives to animal use in aquatic toxicity testing

Lethal Hemorrhage Following Laparoscopic Cholecystectomy Complicated with Medicolegal Issues

This is a case study of unexpected death after laparoscopic cholecystectomy for acute calculous cholecystitis, complicated with medicolegal issues including chronic methamphetamine use and alleged medicolegal malpractice. The deceased underwent a laparoscopic cholecystectomy following acute calculous cholecystitis, and died on the fourth day after the surgery. Postmortem examination revealed massive peritoneal hemorrhage and the cystic artery on the surgical site was cauterized but unligated. Histopathology of the gallbladder revealed acute inflammation due to gall stones but also ischemic change. As the investigation progressed, a history of chronic methamphetamine use was discovered, however, acute methamphetamine toxicity was excluded by toxicological test. Thus, we suggest forensic considerations based on a review of the literature in the interpretation of the pathology of the gallbladder, the unligated cystic artery and cholecystectomy, and chronic methamphetamine use.

Investigating the Potential of Microbially Induced Carbonate Precipitation Combined with Modified Biochar for Remediation of Lead-Contaminated Loess

Lead (Pb) contamination in loess poses a significant environmental challenge that impedes sustainable development. Microbially induced carbonate precipitation (MICP) is an innovative biomimetic mineralization technology that shows considerable promise in remediating soil contaminated with heavy metals. However, the toxicity of lead ions to Bacillus pasteurii reduces the efficiency of mineralization, subsequently diminishing the effectiveness of remediation. Although biochar can immobilize heavy metal ions, its adsorption instability presents a potential risk. In this study, we first compared the pH, electrical conductivity (EC), unconfined compressive strength (UCS), permeability coefficient, and toxicity leaching performance of lead-contaminated loess specimens remediated using biochar (BC), red mud (RM), red-mud-modified biochar (MBC), and MICP technology. Additionally, we evaluated the mechanism of MICP combined with varying amounts of MBC in remediating lead-contaminated loess combing Zeta potential, X-ray diffraction (XRD) analyses, and scanning electron microscopy (SEM) tests. The results showed that MICP technology outperforms traditional methods such as RM, BC, and MBC in the remediation of lead-contaminated loess. When MICP is combined with MBC, an increase in MBC content results in a higher pH (8.71) and a lower EC (232 us/cm). Toxic leaching tests reveal that increasing MBC content reduces the lead leaching concentration in loess, with optimal remediation being achieved at 5% MBC. Microscopic analysis indicates that the remediation mechanisms of MICP combined with MBC involve complexation, electrostatic adsorption, ion exchange, and precipitation reactions. The synergistic application of MICP and MBC effectively adsorbs and immobilizes lead ions in loess, enhancing its properties and demonstrating potential for pollution remediation and engineering applications.

Effects of Berberis asiatica, Withania somnifera, and Their Combination on Body Weight in Streptozotocin-Nicotinamide-Induced Type 2 Diabetes in Wistar Rats.

Introduction Type 2 diabetes mellitus (T2DM) is characterized by insulin resistance, impaired insulin secretion, and beta cell dysfunction, often leading to chronic hyperglycemia and associated complications. Berberis asiatica (BA) and Withania somnifera (WS) are ancient medicinal plants with a reputation for having potential therapeutic effects in diabetes management. The purpose of this study was to look into how body weight (BW) was affected in streptozotocin-nicotinamide (STZ-NIC) induced T2DM in Wistar rats by BA, WS, and their polyherbal combination (PHC). Materials and methods Seventy-eight Wistar rats of both sexes were divided into 13 groups, with six rats in each group, including normal and diabetic controls, and treated with varying doses of BA, WS, and PHC. The rats were under observation over the course of 35 days for any change in BW. The Organization for Economic Co-operation and Development (OECD) rules and guidelines were followed in the conduct of acute toxicity tests. One-way analysis of variance (ANOVA), followed by Tukey-Kramer post hoc tests, was used for statistical analysis. Results The findings indicated that the highest dose of BA (1000 mg/kg) significantly improved BW in diabetic rats, approaching that of the normal control group. The combination of BA and WS also demonstrated significant improvements in BW, suggesting a synergistic effect. The standard antidiabetic drugs, metformin and glimepiride, were effective in increasing BW in diabetic rats. Conclusion The study concludes that BA, WS, and their combination have a positive impact on BW management in T2DM rats, with the combination therapy showing enhanced effects. These findings support the potential utilization of these herbs in managing BW and other T2DM-associated metabolic disturbances and abnormalities.

Changes in Prenatal Cannabis Use Among Pregnant Individuals From 2012 to 2022.

This population-based cross-sectional study analyzed electronic health record data of pregnant individuals in an integrated health care delivery system in California to examine changes in prenatal cannabis use through self-report and urine toxicology testing during standard prenatal care between 2012 (n=33,546) and 2022 (n=43,415), and to test whether trends differed by race and ethnicity or age. The prevalence of prenatal cannabis use increased from 5.5% (95% CI, 5.3-5.8%) in 2012 to 9.0% (95% CI, 8.7-9.2%) in 2022 (adjusted prevalence ratio [aPR] 1.82, 95% CI, 1.72-1.92), with similar increases by toxicology test (aPR 1.70, 95% CI, 1.60-1.81) and self-report (aPR 2.12, 95% CI, 1.95-2.30). The increase in prevalence varied significantly across racial and ethnic and age groups, with the highest prevalence among Black individuals and those aged 13-24 across years. Although rates increased more slowly among groups with the highest prevalence of use, disparities persisted over time.

Analyze and assess the spectral, DFT, and medicinal characteristics through targeted pharmacological investigation of 2-(3-(5-(4-chlorophenyl)furan-2-yl)acryloyl)-3,4-dihydro-2H-naphthalen-1-one (CHFADN)

The compound 2-(3-(5-(4-chlorophenyl)furan-2-yl)acryloyl)-3,4-dihydro-2H-naphthalen-1-one (CHFADN) was synthesized using the Claisen-Schmidt condensation method, reacting aromatic aldehydes with methyl ketones. Characterization was performed using NMR, FTIR, and UV–visible spectroscopy. A theoretical model was developed with Gaussian 09 software, utilizing the B3LYP/6–311++G(d,p) basis set, to investigate geometric, electronic, and spectroscopic properties, including geometry optimization, harmonic vibration simulations, molecular electrostatic potential (MEP), frontier molecular orbitals (FMOs), and Mulliken's population analysis. A scaling factor of 0.9600 ensured alignment between the compound's vibrational spectrum and the experimental IR spectrum.In-vitro testing showed notable bactericidal efficacy,H2O2 scavenging activity and antidiabetic activity. In silico molecular docking using AutoDock 4.0, focusing on the 1HD2 protein's active pocket, revealed a binding interaction energy of -6.5 kcal/mol. ADME properties were predicted based on retention data (RM0). The compound showed no mutagenic effects in toxicity testing, indicating a promising safety profile for new drug candidates.

Submicron immunoglobulin particles exhibit FcγRII-dependent toxicity linked to autophagy in TNFα-stimulated endothelial cells

In intravenous immunoglobulins (IVIG), and some other immunoglobulin products, protein particles have been implicated in adverse events. Role and mechanisms of immunoglobulin particles in vascular adverse effects of blood components and manufactured biologics have not been elucidated. We have developed a model of spherical silica microparticles (SiMPs) of distinct sizes 200–2000 nm coated with different IVIG- or albumin (HSA)-coronas and investigated their effects on cultured human umbilical vein endothelial cells (HUVEC). IVIG products (1–20 mg/mL), bare SiMPs or SiMPs with IVIG-corona, did not display significant toxicity to unstimulated HUVEC. In contrast, in TNFα-stimulated HUVEC, IVIG-SiMPs induced decrease of HUVEC viability compared to HSA-SiMPs, while no toxicity of soluble IVIG was observed. 200 nm IVIG-SiMPs after 24 h treatment further increased ICAM1 (intercellular adhesion molecule 1) and tissue factor surface expression, apoptosis, mammalian target of rapamacin (mTOR)-dependent activation of autophagy, and release of extracellular vesicles, positive for mitophagy markers. Toxic effects of IVIG-SiMPs were most prominent for 200 nm SiMPs and decreased with larger SiMP size. Using blocking antibodies, toxicity of IVIG-SiMPs was found dependent on FcγRII receptor expression on HUVEC, which increased after TNFα-stimulation. Similar results were observed with different IVIG products and research grade IgG preparations. In conclusion, submicron particles with immunoglobulin corona induced size-dependent toxicity in TNFα-stimulated HUVEC via FcγRII receptors, associated with apoptosis and mTOR-dependent activation of autophagy. Testing of IVIG toxicity in endothelial cells prestimulated with proinflammatory cytokines is relevant to clinical conditions. Our results warrant further studies on endothelial toxicity of sub-visible immunoglobulin particles.

The solar/chlorine system degradation of iopamidol: Roles of reactive species, degradation pathway, and toxicity

The study systematically examined the changing trends of the percentage contributions of reactive species to the degradation of Iopamidol (IPM) under various conditions in the solar/chlorine system. Results showed that compared with chlorine alone and solar radiation system, the solar/chlorine system had an obvious effect on the degradation of IPM under control experiment conditions. HO• and reactive chlorine species played major roles in the apparent pseudo-first-order rate constants of IPM degradation (kobs). The increase of oxidant dosage significantly promoted the steady-state concentration of RCS and the contributions of those to kobs. The concentrations of various radicals at pH 9 were lower than those of at pH 5, while only the percentage contribution of ClO• on kobs was increased. The presence of Cl- could increase the steady-state concentration of Cl•, which further promoted the kobs. NOM would significantly reduce the steady-state concentration of ClO• and Cl•, which leads to a significant increase in the percentage contribution of Cl2−• to kobs, indicating the important role of Cl2−• on organic removal in real water. HCO3-/CO32- had almost no effect on kobs. The degradation products of IPM were identified through HPLC-MS, and the Fukui function was employed to ascertain the sites of degradation, which were formulated by deiodination reactions and the production of organic radicals. According to structure Activity Relationships Program v.2.2 and acute toxicological tests, byproducts did not exhibit significant toxicity. The findings illustrate that the solar/chlorine system is effective in decomposing IPM into non-toxic and non-hazardous small molecules, with potential applications.

BBPT attenuated 6-OHDA-induced toxicity by modulating oxidative stress, apoptotic, and inflammatory proteins in primary neurons and rat models of Parkinson's Disease

Parkinson’s disease (PD) results from the degeneration of dopaminergic neurons in substantia nigra pars compacta (SNpc). Adenosine A2AR acting through the striato-pallidal pathway has emerged as a non-dopaminergic target in the therapy of PD. In the present work, the anti-parkinsonian potential of (4E)-4-(4-bromobenzylideneamino)-3-phenyl-2,3-dihydro-2-thioxo- thiazole-5-carbonitrile (BBPT) was explored. BBPT exhibited significant antioxidant activity in situ. In the MTT assay, the BBPT treatment showed insignificant toxicity to the primary midbrain neuronal (PMDN) cells. 6-OHDA induced PMDN cells, 3h post-treated with BBPT showed 80-85% survival of the cells and restoration of dopamine and TNF-α levels. The acute and sub-acute toxicity test for BBPT was performed with Sprague Dawley (SD) rats. In toxicity assay, any significant physical, hematological, or biochemical changes in the rats were not observed. To evaluate the effect of BBPT in vivo, a 6-OHDA-induced unilaterally lesioned SD rat model of PD was established. We observed that the BBPT treatment improved the behavioral symptoms in 6-OHDA-induced unilaterally lesioned rats. The proteins of 6-OHDA-induced BBPT-treated rats were isolated from the brain tissue to assess the antioxidant effect (GSH, catalase, SOD, lipid-peroxidation, nitrite), dopamine levels, and the restoration in the apoptosis and inflammation. Our results demonstrated that BBPT increased the anti-oxidant enzyme levels, restored the caspase-3/Bcl-2 levels to arrest apoptosis, and attenuated the TNF-α/IL-6 levels, thus restoring the neuronal damage in unilaterally lesioned 6-OHDA-induced SD rats. Precisely, the findings suggested that BBPT possessed significant anti-parkinsonian activity and has the potential to prevent dopaminergic neurodegeneration.

Ecotoxicological assessment of waste foundry sands and the application of different classification systems.

The application of a battery of bioassays is widely recognized as a useful tool for assessing environmental hazard samples. However, the integration of different toxicity data is a key aspect of this assessment and remains a challenge. The evaluation of industrial waste leachates did not initially undergo any of the proposed integration procedures. This research addressed this knowledge gap. Twenty-five samples of waste foundry sands were subjected to a leaching test (UNI EN 12457-2) to evaluate waste recovery and landfill disposal. The leachates were evaluated using a battery of standardized toxicity bioassays composed of Aliivibrio fischeri (EN ISO 11348-3), Daphnia magna (UNI EN ISO 6341), and Pseudokirchneriella subcapitata (UNI EN ISO 8692), both undiluted and diluted. Daphnia magna and P. subcapitata were the most affected organisms, with significant effects caused by 68% and 64% of undiluted samples, respectively. The dilution of samples facilitates the calculation of EC50 values, which ranged from greater than the highest concentration tested to 2.5 g/L for P. subcapitata. The data on single-organism toxicity were integrated using three methods: the Toxicity Classification System, the toxicity test battery integrated index, and the EcoScore system. The three classifications were strongly similar. According to all applied systems, three samples were clearly nontoxic (from iron casting plants) and two were highly toxic (from steel casting plants). Moreover, the similar ranking between undiluted and diluted leachates suggests the possibility of using only undiluted leachates for a more cost-effective and time-efficient screening of waste materials. The findings of this study highlight the usefulness of integrating ecotoxicological waste assessment. Integr Environ Assess Manag 2024;00:1-18. © 2024 The Author(s). Integrated Environmental Assessment and Management published by Wiley Periodicals LLC on behalf of Society of Environmental Toxicology & Chemistry (SETAC).

Soil pollution identification and human health risk assessment of soil heavy metals in an abandoned mine area in the Republic of Korea

ABSTRACT In this study, the Geo-accumulation index (Igeo), Human Health Risk Assessment (HRA), and Ecological Risk Index (ERI) were utilized to examine the risks associated with the soils at the DaeyangYeongseong mine. Brassica juncea and Raphanus sativus were employed in the ecological toxicity test. In all soil samples, the mean Igeo value of arsenic measured 3.15, and cadmium measured 6.63, indicating a very high level of heavy metal contamination. The carcinogenic risk of cadmium and arsenic for adults was 4.30×10−3 and 1.43×10−5, respectively. For children, these values were 3.92 × 10−2 and 1.33 ×10−4, exceeding the acceptable level (1×10−6). In all soils, cadmium showed extremely high ecological risk levels, and arsenic had extremely high risk levels in 34.8% of the total area. This was also confirmed in toxicity assessments using plants. Therefore, arsenic and cadmium were found to be the main causes of soil contamination and ecological risk.