Frontiers in toxicology最新文献

Nanoenergetics are defined as a class of nanomaterials that possess the ability to release energy in certain situations. These properties have been studied and deepened in recent years, so much so that nanoenergetics have been introduced into the use of the weapons industry, among others. It is therefore an emerging reality that deserves attention with regard to potential harmful effects on human and environmental health. it has been suggested that nanoenergetics may have genotoxic and immunotoxic effects, among others. Problems related to exposure to nanonenergetics can therefore potentially affect both exposed workers (both in the production and use phase) and the civilian population, if used in war scenarios, for example,. Starting from these assumptions, the INNOTOX research project aims to contribute to the in-depth study of the toxicity of nanonenergetics, through an integrated approach involving experts in occupational and forensic medicine, nanotoxicology and bioengineering.

Introduction: Geometric aquaculture growth has resulted in exponentially increasing use of agrochemicals as either parasiticides or herbicides in the aquaculture environment. This study determines some of the toxicological (haematological and biochemical) effects of glyphosate-based herbicides on non-target aquatic animals using Clarias gariepinus as the animal model.

Method: Seventy-five apparently healthy adult C. gariepinus (300 g) were sourced from a local farmer and acclimatised for 2 weeks; of these, sixty subjects were divided into four treatment groups (fifteen fish per group and five replicates per unit) by simple randomisation and labelled as T0 (control), T1 (first treatment), T2 (second treatment), and T3 (third treatment). The treatments were replicated thrice. Four concentrations of Force up^® [0 mL, 0.15 mL (0.003 mL/L or 5.1 mg/L), 0.225 mL (0.0045 mL/L or 7.65 mg/L), and 0.3 mL (0.006 mL/L or 10.2 mg/L) were added to a 50-L tank of water for T0, T1, T2, and T3, respectively. Approximately 5 mL of blood was collected from the fish in each treatment group 96 h post-exposure for measurement of the blood parameters and biochemical indices using standard analytical methods as well as calculation of the mean values.

Result: The mean values of the packed cell volume, haemoglobin concentration, red blood cell count, and white blood cell count compared to the control group showed an initial increase at T1 but decreased as the glyphosate concentrations increased at T2 (0.0045 mL/L) and T3 (0.006 mL/L). The platelet mean values decreased at T1, increased at T2, and decreased at T3, while the mean values of the corpuscular volume, corpuscular haemoglobin, and corpuscular haemoglobin concentration increased with glyphosate concentration, with the mean corpuscular haemoglobin concentration decreasing at T2. Only the platelet value was statistically significant at a p-value of <0.05 using ANOVA and post hoc Tukey test. The biochemical indices showed decreases in the mean values of aspartate transaminase, blood urea nitrogen, creatinine, and triglycerides at T1, increases at T2, and decreases at T3, while the total protein (g/dL), cholesterol, alanine transaminase, and alkaline phosphatase values showed increases at T1 and decreases at T2 and T3. All these values were not statistically significant based on ANOVA and had p-values >0.05.

Discussion: Based on the results of this study, it is deduced that glyphosate-based herbicide (Force up^®) has genotoxic, hepatotoxic, and nephrotoxic effects on C. gariepinus even at sublethal doses, with more adverse effects at increasing concentrations.

Introduction: In response to the growing need to evaluate nanomaterial (NM) toxicity and compliance with the "3Rs" principles (replacement, reduction, and refinement of animal experiments), zebrafish (Danio rerio) embryos have emerged as a promising alternative model for studies on NM toxicity. However, zebrafish embryos are surrounded by an acellular envelope, the chorion, which limits the permeability of NMs. The present study investigated the importance of dechorionated zebrafish embryos for evaluating NM toxicity.

Methods: We utilized confocal microscopy and field-emission scanning electron microscopy with energy-dispersive spectroscopy to observe the permeability of NMs into the embryonic body using 50-nm fluorescein 5 (6)-isothiocyanate-incorporated silica nanoparticles (FITC-SiO₂NPs). We investigated the physiological effects of removing the chorion using pronase on zebrafish embryos. Nanotoxicity was compared depending on the presence or absence of the chorion in zebrafish embryos using the standardized method ISO/TS 22082:2020.

Results: The FITC-SiO₂NPs were adsorbed onto the embryonic chorion; the Si content was higher in the chorion than in the embryonic body and higher in the intact zebrafish embryos than in the dechorionated ones. Dechorionated zebrafish embryos exhibited no negative physiological effects. The LC₅₀ values of several NMs were lower in dechorionated embryos than those in intact ones.

Conclusion: Dechorionated zebrafish embryos exhibited greater sensitivity to NMs than usual. To the best of our knowledge, this is the first study to evaluate NM toxicity using a new standardized test method, ISO/TS 22082:2020, and could contribute towards the increased utility of dechorionated embryos as an alternative model for the evaluation of nanotoxicity.

Introduction: Periodontitis, affecting approximately 3.9 billion individuals globally, significantly impacts quality of life and has raised interest in its potential systemic effects. Sodium perborate, a common component in oral care products for biofilm control, is widely used, though concerns about its safety persist. This study aimed to evaluate the in vitro toxicity of six commercial oral care products and varying concentrations of sodium perborate, utilizing human gingival fibroblasts (HGF) and keratinocytes (HaCat) as cell models.

Methods: Experiments were performed in both 2D monolayer and 3D cultures using MTT and electrical impedance assays, adhering to the manufacturer's recommended exposure time of 30-60 s for product testing. For the reconstructed epidermis model, a prolonged exposure time of 42 min was applied, following the Organization for Economic Cooperation and Development (OECD) Test Guideline 439.

Results: Results indicated that all products and sodium perborate at 1 mg/mL were cytotoxic in monolayer cultures. However, at concentrations relevant to commercial formulations (0.06 mg/mL sodium perborate), no significant toxicity was observed. In contrast, the 3D culture models, including spheroids and reconstructed epidermis, exhibited minimal to no cytotoxic effects for the commercial products, with sodium perborate showing no significant toxicity below 0.1 mg/mL. The reconstructed epidermis model, used as surrogate for oral mucosa, further confirmed that the products were non-irritating, in compliance with OECD TG 439 standards.

Discussion: This study highlights the importance of considering exposure time, dosage, and cellular model when assessing the safety of oral care products. While 2D models are useful for preliminary screenings, 3D models provide a more physiologically relevant assessment, emphasizing the need for robust testing protocols to ensure product safety.

Introduction: As part of a wider programme of work developing next-generation risk assessment approaches (NGRA) using non-animal methods (NAMs) for safety assessment of materials, Unilever SEAC is exploring the use of a peripheral blood mononuclear cell (PBMC) system to investigate how cells from different arms of the human immune system are impacted by different treatments. To maximise human relevance, the cell cultures are supported by human serum, but this came with some challenges, including an inability to measure induced levels of immunoglobulins due to high background levels. Therefore, a study comparing use of human sera containing media with three different chemically defined serum-free media was undertaken.

Materials and methods: PBMC were isolated from healthy donors and cultured in the absence (media alone) or presence of stimulation reagents (CpG-ODN plus IL-15, Pokeweed Mitogen (PWM) or Cytostim (CS)), in RPMI plus human serum, AIM-V, CTS OpTmizer T cell expansion SFM or X-VIVO 15 media. T cell (CD4⁺ and CD8⁺) and B cell proliferation and viability were measured after 6 days, along with levels of total IgG in the cell culture supernatants.

Results: Each of the serum-free media tested supported good levels of viable and proliferating T cells and B cells over the 6 days of culture, with only a few, small differences across the media, when there was no stimulation. They also enabled detection of a stimulation-evoked increase in IgG levels. There were however some differences in the viability and proliferation responses of T and B cells, to different stimuli, across the different media.

Discussion: The serum-free media formulations tested in this study offer defined systems for. measuring B cell IgG responses, in vitro, in either a 'T cell-independent' (CpG + IL-15) or "T cell-dependent" (PWM or CS) manner and for assessing B cell proliferation, particularly in response to a "T cell-independent" stimulus. However, there are some characteristics and features endowed by human serum that appear to be missing. Therefore, further work is required to optimise animal-free, chemically defined culture conditions for PBMC based assays for inclusion in tiered safety assessments.

The essential use concept aims to better protect consumers, vulnerable groups, and the environment from the most harmful chemicals by phasing out uses considered non-essential for society. Given the lack of empirical research evaluating this novel approach for chemical management in real-world settings, the aims of the present analysis were to 1) investigate if the information provided in applications for authorisation under REACH allowed for the identification of non-essential uses of substances of very high concern (SVHCs), and 2) identify data gaps, challenges and potential needs for revising the assessment criteria to effectively implement the essential use concept in the REACH authorisation. In total, 100 uses covering 11 SVHCs were analysed. 4-(1,1,3,3-tetramethylbutyl) phenol (OPnEO) and chromium trioxide were among the most frequently used substances, covering 42% and 35% of the analysed uses. Using the current essential use criteria, 55% of all analysed uses were categorised as essential, while 10% were categorised as non-essential. Potentially, authorisations would not have been granted for the identified non-essential uses under REACH if the concept had been implemented at the time. However, for 35% of the uses it was not possible to assess their essentiality and these uses were therefore categorised as "complex." These challenges were due to the multiple purposes of the technical function, lack of detailed information on the spectrum of end-uses, and difficulties in interpreting the essential use criteria. Consequently, for a successful implementation of the essential use concept, we recommend the European Commission to develop guidance for applicants and refine the essential use criteria to ensure a transparent and resource-efficient authorisation procedure under REACH.

Gonoderma lucidum (G. lucidum) and Cordyceps militaris (C. militaris) are among the many mushrooms known for their long history of use in traditional medicine. Wildcrafted sources of mushrooms including G. lucidum and C. militaris can be limited from a scarcity and quality perspective, but solid fermentation processes in cultivation settings can provide an efficient way to deliver whole mushroom preparations of a consistent composition. Despite the historical use of these mushrooms, few published reports have explored their potential subchronic oral toxicity or genotoxicity, either from specific components or whole mushroom preparations. The purpose of this study was to assess the potential for acute toxicity, subchronic toxicity, and genotoxicity of powders produced from G. lucidum mycelial biomass and fruiting body ("Organic Reishi M2-102-02 powder") cultured on oats, and C. militaris mycelial biomass, stroma, and fruiting body ("Organic Cordyceps M2-116-04 powder") cultured on oats. Results of the testing demonstrate that both Organic Reishi M2-102-02 powder and Organic Cordyceps M2-116-04 powder were not acutely toxic, did not exhibit subchronic oral toxicity in rats at doses up to the highest dose tested of 2,000 mg/kg bw/day, and did not have genotoxic potential based on in vitro and in vivo genotoxicity assays.

For many industrial chemicals toxicological data is sparse regarding several regulatory endpoints, so there is a high and often unmet demand for NAMs that allow for screening and prioritization of these chemicals. In this proof of concept case study we propose multi-gene biomarkers of compounds' ability to induce lung fibrosis and demonstrate their application in vitro. For deriving these biomarkers we used weighted gene co-expression network analysis to reanalyze a study where the time-dependent pulmonary gene-expression in mice treated with bleomycin had been documented. We identified eight modules of 58 to 273 genes each which were particularly activated during the different phases (inflammatory; acute and late fibrotic) of the developing fibrosis. The modules' relation to lung fibrosis was substantiated by comparison to known markers of lung fibrosis from DisGenet. Finally, we show the modules' application as biomarkers of chemical inducers of lung fibrosis based on an in vitro study of four diketones. Clear differences could be found between the lung fibrosis inducing diketones and other compounds with regard to their tendency to induce dose-dependent increases of module activation as determined using a previously proposed differential activation score and the fraction of differentially expressed genes in the modules. Accordingly, this study highlights the potential use of composite biomarkers mechanistic screening for compound-induced lung fibrosis.

Cannabinoid hyperemesis syndrome presents as a complex of symptoms and signs encompassing nausea, vomiting, abdominal pain, and hot water bathing behavior, most typically in a heavy cannabis user. Its presentation is frequently associated with hypothalamic-pituitary-adrenal axis activation with stress and weight loss. Recent investigation has identified five statistically significant mutations in patients distinct from those of frequent cannabis users who lack the symptoms, affecting the TRPV1 receptor, two dopamine genes, the cytochrome P450 2C9 enzyme that metabolizes tetrahydrocannabinol, and the adenosine triphosphate-binding cassette transporter. The syndrome is associated with escalating intake of high potency cannabis, or alternatively, other agonists of the cannabinoid-1 receptor including synthetic cannabinoids. Some patients develop environmental triggers in scents or foods that suggest classical conditioned responses. Various alternative "causes" are addressed and refuted in the text, including exposure to pesticides, neem oil or azadirachtin. Nosological confusion of cannabinoid hyperemesis syndrome has arisen with cyclic vomiting syndrome, whose presentation and pathophysiology are clearly distinct. The possible utilization of non-intoxicating antiemetic cannabis components in cannabis for treatment of cannabinoid hyperemesis syndrome is addressed, along with future research suggestions in relation to its genetic foundation and possible metabolomic signatures.