Nanoplastics (1-1000 nm) (NPs) represent a novel and insidious class of emerging contaminants with the potential to profoundly disrupt gut microbial ecology and accelerate the spread of antibiotic resistance two critical and converging threats to global health. While prior studies have examined the toxicokinetics of NPs and their general microbial interactions, this review provides the first comprehensive synthesis specifically focused on the nexus between NPs, gut dysbiosis, and the propagation of antibiotic resistance genes (ARGs). This review highlights how NPs alter gut microbiota composition, suppressing beneficial microbes while fostering opportunistic pathogens and how such imbalances may contribute to human health issues. Importantly, emerging evidence also suggests that NPs may serve as unrecognized vectors for horizontal gene transfer (HGT), enabling the rapid dissemination of ARGs conjugation, transformation, transduction, and extracellular vesicles within the gastrointestinal tract. In addition, this review also identifies urgent methodological gaps in detecting NPs in biological matrices and the environment, as well as assessing their mechanistic impacts, calling for innovation in analytical approaches. By presenting an interdisciplinary perspective that bridges nanotoxicology, microbiome science, and antimicrobial resistance, this article sheds light on an underexplored yet urgent frontier in environmental health, offering novel insights to guide future research, risk assessment, and policy development.

Pyrrolizidine alkaloids (PAs) form a family of toxic and carcinogenic phytochemicals found in plants worldwide. The metabolism of toxic PAs, both and , generates four (±)-6,7-dihydro-7-hydroxy-1-hydroxymethyl-5-pyrrolizine (DHP)-derived DNA adducts, namely, DHP-dG-3, DHP-dG-4, DHP-dA-3, and DHP-dA-4, as documented in previous research. We have proposed that these DHP-DNA adducts play a pivotal role in the induction of liver tumor by PAs in rats and mice, serving as potential common biological biomarkers for PA exposure and carcinogenesis. In this study, we found that the metabolism of PAs and PA -oxides by human liver microsomes, in the presence of calf thymus DNA, results in the formation of DNA adducts. This process serves as a convenient and biologically significant platform for investigating the structure-carcinogenicity relationships of PAs.

Nitrate contamination in drinking water poses significant health risks, particularly in rapidly urbanizing areas of developing countries. This study presents an integrated computational and graphical approach to evaluate the geochemistry and health risks of nitrate-contaminated water for six age groups in Southeast, Nigeria. The research employed a detailed methodology combining water nutrient pollution index (WNPI), nitrate pollution index (NPI), water pollution index (WPI), geochemical plotting techniques, stoichiometry, and health risk computations. Water samples from several locations were analyzed for physicochemical parameters and nitrate concentrations. Results revealed predominantly acidic conditions and varying levels of nitrate contamination. Geochemical analysis indicated that silicate weathering and ion exchange processes were the primary influences on water chemistry. The WPI identified 14.29% of samples as "extremely polluted" (WPI > 1), while the WNPI classified 7.14% of samples as "moderately polluted" (WNPI > 1). However, the NPI categorized the samples as safe, indicating low nitrate inputs from anthropogenic sources. Health risk assessments indicated low-moderate risks, with the highest total hazard index of 0.839 for the 6-12 months age group; thus, higher vulnerability for infants. Oral exposure was found to be the dominant pathway, contributing over 99.90% to the total risk. This research provides crucial insights for achieving the Sustainable Development Goals (SDGs) related to water quality and public health protection. The integrated approach offers a robust framework for water resource management and interventions in risk-prone areas. Future research should focus on expanding the spatial coverage, incorporating sensitivity analyses, and exploring advanced technologies for real-time monitoring and predictive modeling of water quality.

As the 16 most common cancer globally, oral cancer yearly accounts for some 355,000 new cases. This study underlines that an early diagnosis can improve the prognosis and cut down on mortality. It discloses a multifaceted approach to the detection of oral cancer, including clinical examination, biopsies, imaging techniques, and the incorporation of artificial intelligence and deep learning methods. This study is distinctive in that it provides a thorough analysis of the most recent AI-based methods for detecting oral cancer, including deep learning models and machine learning algorithms that use convolutional neural networks. By improving the precision and effectiveness of cancer cell detection, these models eventually make early diagnosis and therapy possible. This study also discusses the importance of techniques in image pre-processing and segmentation in improving image quality and feature extraction, an essential component of accurate diagnosis. These techniques have shown promising results, with classification accuracies reaching up to 97.66% in some models. Integrating the conventional methods with the cutting-edge AI technologies, this study seeks to advance early diagnosis of oral cancer, thus enhancing patient outcomes and cutting down on the burden this disease is imposing on healthcare systems.

Poly- and per-fluoroalkyl substances (PFAS) are a large group of synthetic compounds having a wide array of use in consumer products and industries, such as fire suppressant foam, nonstick cookware, paper, water-proof textiles, surfactants, aeronautics, and cosmetics. This widespread distribution of PFAS, their capacity to accumulate in living organisms, and their harmful effects represent a rising concern for public health. A multitude of studies have presented information on exposure to PFAS and a broad spectrum of adverse health outcomes through animal models and observational studies. Here, we have reviewed various studies that are related to PFAS toxicity on bone and brain and its underlying mechanisms. PFAS have well-established toxicological effects on bone, such as reduced osteoblastic and increased osteoclastic activity, increased activation of peroxisome proliferator activated receptor-γ (PPAR-γ), and increased expression of WNT11. With respect to brain, PFAS have been linked with autism, somnolence, sleep disturbances, glioma, Alzheimer's, decreased cognition, increased expression of Glycogen Synthase β (GSK3β). Further research is required in several areas, such as age-specific toxicological effects of PFAS, impact of various other PFAS compounds beyond perfluorooctane sulfonate (PFOS) and perfluorooctanoic acid (PFOA), and involvement of peroxisome proliferator-activated receptors in PFAS-induced toxicity. Regarding brain toxicity, extensive research in adults is required as there is currently a relative scarcity of studies in this age group when compared to the available research conducted on children and older individuals.

Environmental contaminants potentially associated with thyroid cancer are found in Superfund sites, areas the United States Environmental Protection Agency (EPA) has listed for cleanup. This study investigated the association between thyroid cancer incidence rates and Superfund density for sites containing certain contaminants that have been found to be potentially associated with thyroid cancer. Public data on thyroid cancer incidence rates (2015-2019; U.S. Centers for Disease Control and Prevention) and Superfund sites (1980-2014; EPA) were used. Multiple linear regressions were conducted to account for potential confounders, including income, race, and ethnicity. The results showed significant, positive correlations between thyroid cancer incidence rates and log Superfund density in counties with at least one Superfund site for total incidence ( = 0.897, SE = 0.169,  < 0.001), female incidence ( = 1.363, SE = 0.169,  < 0.001), and male incidence ( = 0.438, SE = 0.169,  = 0.010). On sensitivity tests of all counties, including those with zero sites, only female thyroid cancer incidence rate was positively, significantly associated with log Superfund density ( = 0.264, SE = 0.053,  < 0.001). Future studies may assess thyroid cancer incidence, Superfund sites, and covariates at the individual and community levels.

Increasing public interest has resulted in the widespread use of non-pharmaceutical cannabidiol (CBD) products. The sales of CBD products continue to rise, accompanied by concerns regarding unsubstantiated benefits, lack of product quality control, and potential health risks. Both animal and human studies have revealed a spectrum of toxicological effects linked to the use of CBD. Adverse effects related to exposure of humans to CBD include changes in appetite, gastrointestinal discomfort, fatigue, and elevated liver aminotransferase enzymes. Animal studies reported changes in organ weight, reproduction, liver function, and the immune system. This review centers on human-derived data, including clinical studies and investigations. Animal studies are also included when human data is not available. The objective is to offer an overview of CBD-related hepatotoxicity, metabolism, and potential CBD-drug interactions, thereby providing insights into the current understanding of CBD's impact on human health. It's important to note that this review does not serve as a risk assessment but seeks to summarize available information to contribute to the broader understanding of potential toxicological effects of CBD on the liver.

Disinfecting swimming pool water plays a crucial role in preventing the spread of harmful bacteria. However, the interaction between disinfectants and precursors can lead to the formation of potentially disinfection by-products (DBPs). Prolonged exposure to these DBPs may pose health risks. This review study investigates recent research advancements concerning the formation, exposure, and regulation of DBPs within swimming pools. It also provides an overview of existing models that predict DBPs generation in pools, highlighting their limitations. The review explores the mechanisms behind DBPs formation under different disinfectant and precursor conditions. It specifically discusses two types of models that simulate the production of these by-products. Compared to drinking water, swimming pool water presents unique challenges for model development due to its complex mix of external substances, human activities, and environmental factors. Existing models can be categorized as empirical or mechanistic. Empirical models focus on water quality parameters and operational practices, while mechanistic models delve deeper into the kinetics of DBPs generation and the dynamic nature of these compounds. By employing these models, it becomes possible to minimize DBPs production, optimize equipment design, enhance operational efficiency, and manage mechanical ventilation systems effectively.

Black cohosh () has been utilized for centuries by Native Americans as a traditional herbal medicine. The rhizome and root extract from black cohosh (BCE) is one of the most popular herbal dietary supplements worldwide. Due to its claimed estrogen-like effects, contemporary uses of black cohosh products are primarily for alleviating menopausal and perimenopausal symptoms. However, recent studies indicate that BCE is not only ineffective for menopausal therapy, but also induces genotoxicity through an aneugenic mode of action (MoA). Adverse effects induced by BCE have been reported in humans, with many case studies documenting outcomes ranging from mild reactions to acute liver damage and even death. Consequently, concerns about the safety of BCE have emerged. There are more than 100 chemical constituents in black cohosh products, including triterpene glycosides (>40 chemicals), polyphenols (>20 chemicals), and nitrogenous compounds (>70 chemicals). Therefore, commercially available BCE products can differ markedly in composition, leading to the potential for variable bioactivities among these complex commercial products. This review presents the latest information on the toxicological effects of BCE from both and experiments and summarizes the adverse effects of BCE in human clinical trials.

Heavy metals are nearly everywhere in the environment, though at low concentrations. They may come to the environment through anthropologinic or natural causes. Their primary means of naturally enriching soils come from the weathering of parent materials. Nevertheless, the usage of agricultural chemicals is equally significant. Rice fields are particularly vulnerable to heavy metal pollution, which harms human health but also lowers soil fertility and agricultural production. Majority of the potentially harmful exposure that humans experience, particularly to cadmium and arsenic, comes from the plant-based foods that we consume. This article focuses on uptake mechanisms of different heavy metals in the plant system with special reference to the responsible genes, their harmful impacts on plants, human beings and overall agricultural soils. Various remedial approaches have been discussed in this article. Numerous techniques have been investigated for the removal of heavy metals from the environment like physicochemical treatment in the soil, use of microbial agents, phytoremediation approaches etc. Traditional heavy metal remediation techniques are limited by processing challenges, costs, and the production of hazardous sludge; thus, research is increasingly directed toward using microbiological agents like bacteria and fungi for the isolation and exclusion of these toxic materials from the environment. Enhancing food safety requires reducing the accumulation of detrimental substances in crops. A molecular knowledge of heavy metals accumulation pathways may allow the design of crop types with much lower harmful substance levels in food.

Luteolin and apigenin, which are abundantly present in various vegetables, fruits, and herbs, have emerged as noteworthy candidates for therapeutic applications. Traditionally recognized for their anti-inflammatory and antioxidant activities, both luteolin and apigenin have recently demonstrated the ability to inhibit cancer cell growth across multiple cancer types and in animal models. This review provides a comprehensive summary of evidence supporting the anticancer effects of luteolin and apigenin, highlighting their mechanisms of action. The review encompasses studies on their effects on liver, lung, gastric, colon, breast, pancreatic, prostate, and skin cancers in animals. We also discuss the toxicity profiles of luteolin and apigenin. Despite the encouraging preclinical results, neither luteolin nor apigenin has yet been proven to be an effective agent against cancer in clinical trials. Therefore, this review also addresses the current challenges in translating the promising anticancer effects of flavones into clinical success, emphasizing the need for further research using advanced animal models and appropriate administration routes to increase the translational value of preclinical studies. This literature review aims to enhance understanding of the anticancer and toxicological effects of luteolin and apigenin, rather than serving as a risk assessment.

This review aims to critically assess the carcinogenic and mutagenic risks associated with firefighting, with a focus on cancer incidence, cancer mortality and other chronic health outcomes. Firefighting is widely recognized as a high-risk occupation due to repeated exposure to hazardous substances, including polycyclic aromatic hydrocarbons (PAHs) and other combustion by-products. An extensive review of empirical studies, meta-analyses, and institutional reports was conducted, considering not only direct fireground exposure but also risks arising from contaminated personal protective equipment (PPE) and indoor air pollution within fire stations. The findings establish a consistent link between firefighting and elevated risks of multiple cancers and chronic diseases. The complexity of modern -firefighting -environments, amplified by evolving materials, under--ventilated fires, and inadequate decontamination practices, further intensifies these risks. The review highlights the urgent need for advanced protective gear, standardized decontamination protocols, routine health surveillance, and policy reforms. It underscores the importance of multidisciplinary collaboration in developing effective strategies to safeguard the health of firefighters, who play a vital role in ensuring public safety.

Humans are continually exposed to a diverse array of environmental chemicals that can damage DNA and compromise genomic integrity. Among these genotoxic agents, acetaldehyde, acrolein, aristolochic acids, and vinyl chloride are particularly concerning due to their widespread presence in industrial emissions, dietary sources, and lifestyle-related exposures such as smoking and alcohol consumption. These compounds can induce structurally distinct forms of DNA damage including bulky DNA adducts, interstrand crosslinks, and other replication-blocking lesions. While canonical DNA repair pathways serve as the primary defense against such DNA damage, some lesions persist, challenging the capacity of DNA repair systems. If not efficiently repaired, DNA lesions may disrupt replication and transcription. In many cases, translesion synthesis polymerases are recruited to bypass unrepaired lesions, introducing mutations that contribute to agent-specific mutational signatures found in cancer genomes. This review systematically examines how each of these four exogenous chemicals induces DNA damage, the DNA repair pathways responsible for removing their lesions, and the role of translesion synthesis in shaping their mutational signatures. We also highlight how three-dimensional genome organization regulates lesion susceptibility and repair, contributing to variability of mutational landscapes.

Accurately evaluating chemical risk may benefit from the development of human-relevant models capable of capturing the effects of treatments that closely mimic real-world environmental and pharmaceutical exposures. Building on our previous work (Seo et al. Arch Toxicol 98:1919-1935), where cytotoxicity compromised mutation detection following short-term treatments, this study investigated mutation accumulation in both 2D and 3D HepaRG cultures following 7- and 14-day exposures with relatively non-cytotoxic -nitrosodimethylamine (NDMA) concentrations. A multi-endpoint approach was employed to assess NDMA-induced DNA damage, micronucleus formation, and mutagenesis. Seven-day NDMA treatments were not cytotoxic but produced concentration-dependent increases in DNA damage and mutations. After 14 days of exposure, the highest NDMA concentrations produced no more than 30% cytotoxicity, and induced greater mutation frequencies compared to the 7-day exposures. Overall, the mutation frequencies induced by NDMA exhibited concentration- and treatment-duration-dependent relationships in both 2D and 3D HepaRG cultures, with notably higher mutation frequencies in 3D spheroids than in 2D cultures. Quantitative analysis by benchmark concentration (BMC) modeling demonstrated lower BMC values in 3D spheroids compared to their 2D counterparts. The predominant mutation in NDMA-treated cultures was T→C transition. These findings indicate the value of extended exposure periods for conducting genotoxicity testing in HepaRG cells.

Monosodium glutamate (MSG) is a food additive that enhances the palatability of foods, thus its frequent use both domestically and industrially. Based on the dose-factor, frequency, and duration of exposure, MSG may provoke adverse health outcomes both in animals and humans. The present report aims at providing a comprehensive analysis of the scientifically proven untoward health effects of MSG. To achieve our aim, we adopted the PRISMA guidelines and checklist and searched four databases (Scopus, Web of Science, PubMed, and Google Scholar) from 2014 to 2024. Retrieved research papers were critically appraised for quality using the ARRIVE and Joanna Briggs (JB) checklists and data analysis was conducted the narrative synthesis method. Our analysis reveals that though MSG is generally considered safe at low doses; however, high doses and repeated exposure to MSG are associated with embryotoxicity and teratogenicity, obesity, cardiotoxicity, hepatotoxicity, kidney toxicity, neurotoxicity, endothelial dysfunction, reproductive toxicities, alteration of lipid, and glucose metabolism. Thus, chronic exposure to MSG may be of human pathological importance. The findings of the present narrative synthesis provide a rationale for informed decisions on the use and labeling of this widely used food additive.

The escalating apprehension surrounding the carcinogenic potential of chemicals emphasizes the imperative need for efficient methods of assessing carcinogenicity. Conventional experimental approaches such as in vitro and in vivo assays, albeit effective, suffer from being costly and time-consuming. In response to this challenge, new alternative methodologies, notably machine learning and deep learning techniques, have attracted attention for their potential in developing carcinogenicity prediction models. This article reviews the progress in predicting carcinogenicity using various machine learning and deep learning algorithms. A comparative analysis on these developed models reveals that support vector machine, random forest, and ensemble learning are commonly preferred for their robustness and effectiveness in predicting chemical carcinogenicity. Conversely, models based on deep learning algorithms, such as feedforward neural network, convolutional neural network, graph convolutional neural network, capsule neural network, and hybrid neural networks, exhibit promising capabilities but are limited by the size of available carcinogenicity datasets. This review provides a comprehensive analysis of current machine learning and deep learning models for carcinogenicity prediction, underscoring the importance of high-quality and large datasets. These observations are anticipated to catalyze future advancements in developing effective and generalizable machine learning and deep learning models for predicting chemical carcinogenicity.

Early exposure to bisphenol A (BPA) is associated with increased asthma prevalence. To examine the effects of the most widely used BPA substitute, bisphenol S (BPS), on the development of childhood asthma, we conducted the study using the mouse model of early exposure. To simulate the burden from the human chronic exposure, we used a short-term exposure with 10 µg/ml BPS in the drinking water of female BALB/c mice (F0) from one week before pregnancy until the weaning of F1 pups. The pups were sensitized with low doses of ovalbumin (OVA) injection on postnatal day 4 and inhalation of OVA two weeks later. Twenty-four hours after the last inhalation, allergen-specific IgE and IgG1 levels, airway inflammation, and hyperresponsiveness were assessed. Non-OVA-sensitized females were mated with non-exposed male mice for the next generation at eight weeks of age. The resulting pups were sensitized, and the asthma phenotype was examined up to F4. Pups exposed to BPS displayed an asthma phenotype in response to their sensitization. We observed enhanced asthma phenotype in the F1-F4 derived from BPS-exposed F0 females compared to those derived from non-exposed females. Maternal exposure to BPS caused the multigenerational effects on the development of experimental asthma.

Recent discoveries of microplastics in cities, suburbs, and even remote locations, far from microplastic source regions, have raised the possibility of long-distance transmission of microplastics in many ecosystems. A little is known scientifically about the threat that it posed to the environment by microplastics. The problem's apparent size necessitates the rapid development of reliable scientific advice regarding the ecological risks of microplastics. These concerns are brought on by the lack of consistent sample and identification techniques, as well as the limited physical analysis and understanding of microplastic pollution. This review provides insight regarding some unaddressed issues about the occurrence, fate, movement, and impact of microplastics, in general, with special emphasis on primary microplastics. The approaches taken in the earlier investigations have been analyzed and different recommendations for future research have been suggested.

The micronucleus assay is a well-known and established component of the standard genotoxicity test battery. The growing use of nanomaterials around the world along with human exposure to them has increased the need for risk assessment with regard to safety, including potential genotoxicity. The micronucleus assay is one of the most used tests for evaluating the genotoxicity of nanomaterials. This review compiles studies since 2017 that performed assessments of micronucleus formation after cellular exposure to different nanomaterials. Genotoxicity of a broad range of nanomaterials including silver, cerium, zinc, gold, nickel, cadmium, titanium, carbon, and aluminum in different cell types were reviewed. While clear trends could be seen for some nanoparticle types like silver and cerium nanoparticles, others like gold nanoparticles showed mixed results. This review highlights the usefulness and effectiveness of the micronucleus assay for studying the genotoxicity of nanomaterials, in part, and is also careful to note that standard guidelines should be followed when conducting this assay in order to generate reliable and quality-driven data.

Since usnic acid was first isolated in 1844 as a prominent secondary lichen metabolite, it has been used for various purposes worldwide. Usnic acid has been claimed to possess numerous therapeutic properties, including antimicrobial, anti-inflammatory, antiviral, anti-proliferative, and antipyretic activities. Approximately two decades ago, crude extracts of usnic acid or pure usnic acid were marketed in the United States as dietary supplements for aiding in weight loss as a "fat-burner" and gained popularity in the bodybuilding community; however, hepatotoxicity was documented for some usnic acid containing products. The US Food and Drug Administration (FDA) received numerous reports of liver toxicity associated with the use of dietary supplements containing usnic acid, leading the FDA to issue a warning letter in 2001 on a product, LipoKinetix. The FDA also sent a recommendation letter to the manufacturer of LipoKinetix, resulting in the withdrawal of LipoKinetix from the market. These events triggered investigations into the hepatotoxicity of usnic acid and its mechanisms. In 2008, we published a review article titled "Usnic Acid and Usnea Barbata Toxicity". This review is an updated version of our previous review article and incorporates additional data published since 2008. The purpose of this review is to provide a comprehensive summary of the understanding of the liver toxicity associated with usnic acid, with a particular focus on the current understanding of the putative mechanisms of usnic acid-related hepatotoxicity.

The cosmetic and personal care product (PCP) industries have bloomed in the last ten years. Many new brand names have established themselves with various lucrative advertisements, luring youths into their primary customers. Many chemicals infused into daily day-night creams or shampoo conditioners have been established as Endocrine Disrupting Chemicals (EDC). The unseen side of the coin has been flipped in this article in an attempt to relate the rising infertility issue with these products. The study aims to explore the potential adverse effects and risk assessment of the EDCs of cosmetics and personal care products, which highlights a thorough review to indicate whether chemicals such as parabens, phthalates, or UV filters are safe for reproductive physiology. EDCs may cause severe negative impacts on the reproductive systems of both males and females which include reproductive problems such as polycystic ovarian syndrome, hypospadias, cryptorchidism, ovarian cancer, endometriosis, and poor sperm quality. Despite the widespread usage and purchase of cosmetic products in the present world, little research has been conducted on the possible effects of cosmetic EDCs on health. Consequently, further in-depth research needs to be performed in this field for a better understanding of the reproductive risks caused by cosmetic EDCs.