Journal of Xenobiotics最新文献

Modern pesticide risk assessment relies on data on bioaccumulation and acute aquatic toxicity, yet generating such data is labour-intensive and animal-demanding. This study evaluated whether phospholipid affinity of pesticides, quantified by the chromatographic hydrophobicity index CHI_IAM obtained from high-throughput gradient biomimetic chromatography, can serve as a surrogate descriptor of these endpoints. Nineteen pesticides representing different chemical and functional classes were analyzed on IAM.PC.DD2 columns, and CHI_IAM values were determined. Bioconcentration factors (BCF) in fish and acute toxicity data (96 h LC₅₀ for fish, 48 h EC₅₀ for Daphnia magna) were retrieved from the Pesticide Properties DataBase. CHI_IAM ranged from -12.1 to 54.8 and correlated strongly with log₁₀BCF (r = 0.84) and log₁₀LC₅₀ in fish (r = -0.84), and moderately with log₁₀EC₅₀ for Daphnia (r = 0.76). Highly lipophilic pesticides with high CHI_IAM showed elevated BCF and low LC₅₀/EC₅₀ values, whereas polar compounds with low CHI_IAM exhibited negligible bioconcentration and low acute toxicity. Deviations from these trends, for compounds with specific modes of action, highlighted the contribution of mechanisms beyond membrane toxicity. Overall, CHI_IAM measured under high-throughput conditions retains prognostic value for ecotoxicological assessment and may serve as a rapid experimental descriptor to support preliminary screening.

Electronic Nicotine Delivery Systems (ENDSs) expose users to nicotine, volatile organic chemicals, and ultrafine particles that pose emerging toxicological concerns for youth. The prevalence of vaping among college students quadrupled between 2017 and 2019. The Vaping Initiation, Continuation, Termination, or Resumption in Youth (VICTORY) study explored a random sample of 543 undergraduate students at a Midwestern university, using an anonymous online survey, for factors associated with initiation and regular inhalation of vape-derived aerosols. Results showed that 50% of participants had ever used a vape, and 67% had used tobacco, vape, or marijuana. The mean age of first use of tobacco was 15.16 years, significantly younger than the mean ages for vaping (16.33) and marijuana (16.60). There were no significant gender differences in ENDS use, although more males reported tobacco as their first substance (18% difference). Notably, 40% reported non-alcoholic substance or alcohol use in the past 30 days. Decision-tree analysis revealed complex relationships between vaping aerosols, tobacco, alcohol use, marijuana use, and living arrangements. Logistic regression identified key predictors of regular vaping, including higher school year, lower household income, employment status, and younger age at first use. These findings highlight the need for tailored public health interventions and continued monitoring to address the growing trend of youth vaping.

Although cancer biology has advanced considerably, the impact of environmental toxins on carcinogenesis remains underrecognized and scattered across disciplines. Evidence increasingly shows that chronic exposure to a broad range of toxins-including persistent organic pollutants, heavy metals, pesticides, phthalates, microplastics, and fine particulate matter (PM2.5), which significantly contributes to cancer initiation, progression, and treatment resistance. This review synthesizes mechanistic, molecular, and epidemiological findings from 2015 to 2025, identified through systematic searches of PubMed, Scopus, Web of Science, and MeSH. Key pathways include oxidative stress-mediated DNA damage, epigenetic reprogramming (DNA methylation, histone modifications, miRNA dysregulation), hormone receptor modulation, chronic inflammation, immune evasion, and tumor microenvironment remodeling. Case studies of benzene, arsenic, aflatoxins, pesticides, and microplastics detail exposure routes, molecular targets, and associated cancers, highlighting significant public health risks. Ongoing debates persist regarding safe exposure thresholds, latency periods, and the effects of mixed toxin exposures. The review also highlights recent innovations in environmental oncology, including AI-based predictive models, CRISPR screens for susceptibility genes, organoid/3D models, green chemistry interventions, and real-time exposure monitoring, which provide mechanistic insight and inform early detection and personalized prevention strategies. Additionally, regional data gaps, particularly in low- and middle-income countries, indicate the need for stronger interdisciplinary collaboration. By integrating molecular mechanisms, epidemiology, and technological advances, this review offers a comprehensive framework for understanding toxin-induced carcinogenesis and guiding future research, public health policy, and preventive strategies.

Of the Cytochrome P450 enzymes, the CYP2C9 variant is very important in the metabolism of several human drugs, acting as a natural bioscavenger. Previously, CYP2C9 was shown to convert the thion (P=S) to the oxon (P=O) form for some organophosphorus (OP) pesticides, such as dimethoate, diazinon, and parathion. In this study, we tested the ability of CYP2C9 to degrade other OP compounds. We investigated the metabolism of OP compounds by CYP2C9 using LC-MS/MS as well as time-dependent inhibition using the previously developed pFluor50 fluorogenic assay. We found that CYP2C9 metabolizes thions preferentially over oxons, and that many OP compounds inhibit CYP2C9 activity in a time-dependent manner. Additionally, we performed molecular docking based on the crystal structure (1OG5) of the CYP2C9 receptor. We observed a positive, though moderate, correlation between the calculated binding energy and the CYP2C9 metabolism of various OP compounds (R = 0.59). These in vitro data, combined with further analysis and additional OP derivatives, could potentially be used to develop artificial intelligence (AI)/machine learning (ML) models to predict the metabolism of specific OP compounds by CYP2C9. This type of approach could be particularly relevant for the prediction of the metabolism of current and emerging chemical warfare agents.

The metallurgical industry generates substantial amounts of heavy metal-containing solid waste, posing significant environmental and health risks. This study systematically evaluates the environmental behavior and ecological risks of heavy metals in four typical metallurgical wastes: jarosite slag (SW1), electric arc furnace ash (SW2), chromium-containing sludge (SW3), and acid-base sludge (SW4). We demonstrate that particle size fundamentally governs heavy metal mobility, with fine-structured SW1 and SW2 (D₅₀ = 4.76 µm and 1.34 µm) exhibiting enhanced metal mobility and bioavailability. In contrast, coarser SW3 and SW4 particles (D₅₀ = 268.83 µm and 133.94 µm) retain heavy metals in more stable forms. Among all metals analyzed, cadmium (Cd) presents the most severe ecological threat, with acid-extractable fractions reaching 52% in SW2 and 45% in SW3-indicating high release potential under changing pH conditions. Risk assessment confirms high to very high ecological risks for Cd in both SW2 and SW3. Moreover, under acidic leaching conditions, SW1 and SW2 show significantly higher cumulative toxicity than SW3 and SW4. These findings highlight the critical role of waste-specific properties in controlling heavy metal fate and provide a scientific basis for targeted risk management and sustainable remediation strategies.

Silver nanomaterials (Ag NMs) are widely used, including in consumer products, and they inevitably enter the environment, with the soil compartment acting as a major sink. However, most available toxicity data focus on the reference Ag NM300K and rely on standard tests, even though long(er)-term exposure tests are recognized as particularly important for assessing the risks to soil invertebrates. Hence, the aim of the present study was to investigate the toxicity of commercial Ag NPs (Ag-Sigma, NPs < 150 nm) to the soil ecotoxicology model Folsomia candida (Collembola). Effects were assessed based on the standard OECD reproduction test (28 days) and beyond, with exposure prolonged for a second generation (56 days). Results showed that, based on the standard test (50% reproduction effect concentration-EC50 = 988 mg Ag/kg soil), the commercial Ag NPs were less toxic than the reference Ag NM300K and the ionic form AgNO₃ (from literature). However, the toxicity dramatically increased (ca. 4 times) during the second-generation exposure (EC50(56d) = 234 mg Ag/kg soil), surpassing the toxicity of Ag NM300K. The decrease in adults' size indicates that moulting might be affected. Overall, increased toxicity in prolonged exposure was not expected based on the available and standard test results, which highlights the importance of long(er)-term exposures to fully assess the risks of NMs to soil communities.

The use of sweeteners in e-cigarette liquids has become increasingly common, aiming to enhance the sensory appeal of vaping products. Compounds like aspartame, saccharin, and sucralose are added to provide a sweet taste without any calories, especially in flavored e-liquids popular among younger users. However, recent studies suggest that these additives may pose significant health risks when vaporized and inhaled. Sucralose, in particular, can break down into potentially harmful chlorinated by-products at high temperatures typical of vaping devices. Moreover, there is growing concern about the synergistic effects of sweeteners like sucralose, one sweetener with another and when combined with other e-liquid components. It has been observed that the presence of sucralose may amplify oxidative stress; genotoxicity, including mutations; and overall toxicity, along with environmental impact. This is not limited to nicotine- and smoke-related harm, as it may strengthen the toxic effect of the substances used in e-liquids that are not present in traditional cigarettes. The combined exposure to these heated compounds can intensify cytotoxicity, potentially increasing the risk of respiratory, cardiovascular, and neurological effects over time. While marketed as safer alternatives to tobacco, e-cigarettes containing sweeteners like sucralose may introduce new and poorly understood toxicological hazards that deserve urgent regulatory attention.

Triazole fungicides are widely used in agriculture but may pose risks to human health through occupational, accidental, or environmental exposure. This systematic review aimed to evaluate the toxicity of ten European Union-approved triazole fungicides in rodent models and cell lines. A total of 70 studies were included, reporting quantitative in vivo oral, dermal, or inhalation toxicity in mammals or quantitative in vitro cytotoxicity in human or mammalian cell lines; the exclusion criteria comprised publications not in English or not accessible. Literature searches were conducted in Web of Science, Google Scholar, and the Pesticide Properties DataBase (PPDB), and risk of bias in included studies was assessed using ToxRTool. Due to heterogeneity in study designs, reporting formats, and endpoints, data were synthesized descriptively. Quantitative endpoints included LD₅₀/LC₅₀ values for in vivo studies and LOEC, IC₅₀, LC₅₀, and EC₅₀ values for in vitro studies, while mechanistic endpoints highlighted apoptosis, oxidative stress, genotoxicity, and endoplasmic reticulum stress. Difenoconazole and tebuconazole were the most extensively studied compounds, whereas several triazoles had limited data. The limitations included heterogeneity of data and incomplete reporting, which restrict cross-study comparisons. Overall, the findings provide a comprehensive overview of potential human health hazards associated with EU-approved triazole fungicides and highlight critical knowledge gaps. The review was registered in Open Science Framework.

Bisphenol A (BPA), a synthetic industrial compound widely found in plastics and other materials, has been linked to cancer development. As human exposure increases, BPA may pose potential carcinogenic concerns. Although BPA binds to estrogen receptors with much lower affinity than natural estrogens, its accumulation in human tissues can cause harmful effects. This review summarizes current evidence on BPA's role in cancer initiation and progression, with a focus on its effects on cancer signaling pathways. These effects involve modulating pathways involved in cell growth, movement, invasion, survival, and adhesion. BPA acts as an estrogen ligand, binding to estrogen receptors and activating related pathways. The main route of exposure is through dietary intake of canned and plastic-packaged foods, with migration rates increasing at higher temperatures. To raise awareness of BPA's harmful effects, industries have proposed "BPA-free" alternatives, some of which use derivatives like bisphenol S (BPS) and bisphenol F (BPF), which, unfortunately, may have even worse effects on human health. Given the ongoing challenges of eliminating BPA and similar harmful compounds, future research should focus on identifying safe substitutes, developing more effective removal technologies, and strengthening stringent regulations to mitigate public health risks.

In recent years, the expansion of the illicit market for Novel Psychoactive Substances (NPS) has resulted in the emergence of numerous synthetic recreational drugs specifically designed to evade legal control and analytical detection. Among these, nitazenes represent one of the most potent classes of new synthetic opioids, although information regarding their toxicological properties remains limited. The present study aimed to assess the genotoxic potential of four nitazenes: clonitazene, etonitazene, isotonitazene and metonitazene in human lymphoblastoid TK6 cells using a flow cytometric version of the In Vitro Mammalian Cell Micronucleus Test, following OECD Guideline No. 487. Cells were exposed to concentrations ranging from 12.5 to 100 μM, and cytotoxicity, cytostasis, and apoptosis were evaluated to identify appropriate doses for micronucleus frequency assessment. Vinblastine, a well-established mutagen, was included as positive control. Our findings demonstrated that clonitazene and isotonitazene exhibit mutagenic potential, suggesting an increased long-term risk of developing chronic degenerative diseases. Furthermore, the results revealed that structurally related molecules can induce markedly different cellular effects, underscoring the importance of compound-specific toxicological evaluations to achieve a comprehensive understanding of the risks associated with their illicit use-risks often presumed to involve only addiction or acute toxicity.