The increasing use of pesticides has raised global concerns about their ecological safety, especially in aquatic systems. Fosetyl-aluminium (fosetyl-Al), a systemic fungicide, acts by inhibiting fungal growth and stimulating plant defense. In this study, the Ecological Structure–Activity Relationship (ECOSAR) model was applied to predict its acute and chronic toxicity towards aquatic and terrestrial organisms. Results consistently indicated “no effects at saturation,” suggesting minimal acute risk under realistic exposure. These findings, corroborated by experimental data, highlight fosetyl-Al as an environmentally low-risk fungicide and demonstrate the value of QSAR-based in silico approaches in preliminary ecological risk assessment.

Cardiovascular diseases (CVDs) remain a leading cause of mortality in modern society, with factors such as sedentary lifestyles, unhealthy diets, and obesity contributing to their increasing prevalence. The widespread use of Statins for lipid-lowering therapy in both primary and secondary cardiovascular prevention is anticipated to rise in response to this trend. Given the rapid escalation in the prevalence of Statin usage, it is imperative to understand their toxicological effects on public health. While previous studies have explored various pharmacological effects of statins, comprehensive investigations into their genotoxic and Mutagenic potential are lacking. In this study, we conducted a comprehensive In silico evaluation of Statins using four different toxicological assessment programs, focusing on various genotoxicity, carcinogenicity, Mutagenicity, and Micronucleus formation endpoints. By comparing program outputs with experimental data, we assessed the reliability of In silico Toxicity predictions and discussed the consistency among different platforms. Our findings suggest discrepancies among the predictions of different programs, highlighting the importance of integrating multiple sources of data and methodologies in Toxicity evaluations. Despite inconsistencies, integrating in silico predictions with future in vitro and in vivo studies can contribute to a better understanding of the toxicological properties of statins and ensure their safe usage. This study underscores the necessity of careful evaluation and utilization of multiple data sources in decision-making regarding the toxicological profile of statins. Ultimately, leveraging in silico methods to guide future comprehensive toxicological studies will enhance our understanding of Statins' safety profiles and contribute to public health research.

Selective cyclooxygenase-2 (COX-2) inhibitors (coxibs) offer reduced gastrointestinal toxicity compared to traditional non-steroidal anti-inflammatory drugs (NSAIDs), yet their safety remains controversial as evidenced by several market withdrawals due to severe cardiovascular and hepatic risks. This study systematically evaluated 16 human and veterinary coxib compounds for mutagenicity, carcinogenicity, micronucleus activity, and hepatotoxicity through a multi-platform in silico approach using VEGA-QSAR, ToxTree, and T.E.S.T. software. The results indicated that while widely used agents like Celecoxib and Etoricoxib exhibit safer profiles, compounds such as Lumiracoxib and NS-398 possess significant carcinogenic and mutagenic potential. Notably, high-reliability hepatotoxicity alerts were identified for several veterinary-grade coxibs, raising significant public health concerns regarding drug residues in the equine-derived food chain and potential human exposure. Discrepancies observed between different predictive models highlight the limitations of individual algorithms and underscore the necessity of a consensus approach to improve the robustness of risk evaluations. This study provides an essential foundational framework for the safety assessment of coxib derivatives and emphasizes the critical importance of validating in silico alerts with targeted in vivo research, particularly in the context of food safety and drug residue management.

Bu çalışmada, Benalaxyl-M maddesinin bal arıları (Apis mellifera) üzerindeki akut toksik etkileri, makine öğrenimi tabanlı bir QSAR (Kantitatif Yapı-Aktivite İlişkisi) aracı olan BeeToxAI kullanılarak in silico yöntemlerle değerlendirilmiştir. Analiz sonuçları, Benalaxyl-M'nin bal arıları için akut oral ve kontakt toksisite açısından toksik olmadığını (%83-86 güvenilirlik) göstermiştir. Uygulanabilirlik Alanı analizi, tahminlerin güvenilir olduğunu doğrularken, katkı haritaları moleküldeki toksisiteye katkı yapan fonksiyonel grupları belirlemede kullanılmıştır. Elde edilen bulgular, Benalaxyl-M'nin bal arıları üzerindeki düşük akut riskini ortaya koysa da, sonuçların deneysel çalışmalarla desteklenmesi önerilmektedir. Bu çalışma, pestisitlerin ekotoksikolojik risk değerlendirmelerinde yapay zeka tabanlı araçların potansiyelini vurgulamaktadır.

This study evaluates the cytotoxic and genotoxic-like potential of an ipfencarbazone-based herbicide formulation (IPF-BH; commercial product Hokuto, containing 250 g/L of the triazolinone herbicide ipfencarbazone) in human peripheral lymphocytes in vitro across a concentration range of 62.5–1000 µg/mL. Cytotoxicity was monitored via the mitotic index (MI), while cytogenetic damage was assessed using the cytokinesis-block micronucleus (MN) assay and the alkaline comet assays. Comparisons were performed using one-way ANOVA, followed by Dunnett’s post hoc test, against the negative control. Results indicated a concentration-dependent cytotoxic effect, with a marked reduction in MI observed at all tested concentrations (p < 0.001). MN frequency was significantly elevated at concentrations ≥125 µg/mL, whereas the 62.5 µg/mL concentration did not induce significant micronuclei formation. The comet assay revealed increased DNA damage parameters (tail length, tail intensity (%), and tail moment) across the tested concentration range, albeit with a non-monotonic profile for tail length and tail intensity. These findings suggest that IPF-BH exposure is associated with marked cytotoxicity and a genotoxic response in this in vitro model at concentrations within the OECD 487-acceptable cytotoxicity window, together with cytotoxicity-associated genotoxic-like effects at strongly cytotoxic concentrations in human peripheral lymphocytes under in vitro conditions. Because IPF-BH is a commercial formulation, and no direct mechanistic endpoints (e.g., reactive oxygen species, mitochondrial transmembrane potential, lipid peroxidation, glutathione) were measured, and because the present design was performed without exogenous metabolic activation (no S9 supplementation), the observed effects cannot be unambiguously attributed to ipfencarbazone alone or to a defined mechanism of action; extrapolation to in vivo genotoxicity requires complementary +S9 and rodent in vivo follow-up studies.