Frontiers in Toxicology

Dimethyl sulfoxide (DMSO) is a popular solvent for developmental toxicity testing of chemicals and pharmaceuticals in zebrafish embryos. In general, it is recommended to keep the final DMSO concentration as low as possible for zebrafish embryos, preferably not exceeding 100 μL/L (0.01%). However, higher concentrations of DMSO are often required to dissolve compounds in an aqueous medium. The aim of this study was to determine the highest concentration of DMSO that can be safely used in our standardized Zebrafish Embryo Developmental Toxicity Assay (ZEDTA). In the first part of this study, zebrafish embryos were exposed to different concentrations (0-2%) of DMSO. No increase in lethality or malformations was observed when using DMSO concentrations up to 1%. In a follow-up experiment, we assessed whether compounds that cause no developmental toxicity in the ZEDTA remain negative when dissolved in 1% DMSO, as false positive results due to physiological disturbances by DMSO should be avoided. To this end, zebrafish embryos were exposed to ascorbic acid and hydrochlorothiazide dissolved in 1% DMSO. Negative control groups were also included. No significant increase in malformations or lethality was observed in any of the groups. In conclusion, DMSO concentrations up to 1% can be safely used to dissolve compounds in the ZEDTA.

Jente Hoyberghs

Chloé Bars

Miriam Ayuso

Chris Van Ginneken

Kenn Foubert

Steven Van Cruchten

DMSO Concentrations up to 1% are Safe to be Used in the Zebrafish Embryo Developmental Toxicity Assay

浓度高达1%的二甲基亚砜在斑马鱼胚胎发育毒性测试中使用是安全的

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 &amp;lt;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 &amp;gt;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.

Selim Adewale Alarape

Deborah Damilola Adeoye

Azeezat Oluwakemi Amusa

Olanike Kudirat Adeyemo

Haematological parameters and biochemical indices of African catfish (Clarias gariepinus) exposed to glyphosate-based herbicide (Force up®) for 96 hours

非洲鲶鱼（Clarias gariepinus）暴露于草甘膦基除草剂（Force up®）96小时后的血液学参数和生化指标

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.

Lang Tran

Michele Treglia

Luca Coppeta

Cristiana Ferrari

Margherita Pallocci

Luisa Campagnolo

Luiz C. De Miranda Junior

Bruno Piccoli

Sharyn Gaskin

Francisco Cortes Fernandes

Fabio Dantas Filho

Pierluigi Passalacqua

Antonio Pietroiusti

Lorenzo Ippoliti

Mario Bragaglia

Francesca Nanni

Andrea Magrini

Luigi Tonino Marsella

Nanomaterials and security in occupational and forensic medicine: insights from nanotoxicology

职业与法医医学中的纳米材料与安全：纳米毒理学的启示

Laura M. Langan

Michelle Bloor

Amanda Sevcik

Erica D. Bruce

Editorial: Women in environmental toxicology

编者按：环境毒理学中的女性

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.

Stella Cochrane

Ouarda Saib

David Sheffield

Use of serum-free media for peripheral blood mononuclear cell culture and the impact on T and B cell readouts

无血清培养基在外周血单个核细胞培养中的应用及其对T细胞和B细胞检测结果的影响

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-SiO 2 NPs). 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-SiO 2 NPs 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 LC 50 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.

Rosa Kim

Yunwi Heo

Hakwon Yoon

June-Woo Park

Dechorionated zebrafish embryos improve evaluation of nanotoxicity

去膜斑马鱼胚胎提高纳米毒性评估效果

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.

S. Marceli Leano

Wanderson De Souza

Rodrigo De Vecchi

Amanda Lopes

Tatiana Deliberador

Jose M. Granjeiro

A multimodal in vitro approach to assess the safety of oral care products using 2D and 3D cellular models

一种利用二维和三维细胞模型评估口腔护理产品安全性的多模态体外方法

短名	Front. Toxicol.
Journal Impact	3.69
国际分区	TOXICOLOGY(Q2)

ISSN	2673-3080
h-index	15

涉及主题	生物医学化学遗传学内科学生物化学有机化学内分泌学物理心理学基因毒性工程类生态学计算机科学地质学药理学计算生物学病理
出版信息	出版商: Frontiers Media SA，出版周期: ，期刊类型: journal，开源期刊: 是
基本数据	创刊年份: 2019，原创研究文献占比: 0.00%，自引率:5.60%， Gold OA占比: 99.29%
期刊费用	$2125详情
平均审稿周期	网友分享经验：13 Weeks

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DMSO Concentrations up to 1% are Safe to be Used in the Zebrafish Embryo Developmental Toxicity Assay

Haematological parameters and biochemical indices of African catfish (Clarias gariepinus) exposed to glyphosate-based herbicide (Force up®) for 96 hours

Nanomaterials and security in occupational and forensic medicine: insights from nanotoxicology

Editorial: Women in environmental toxicology

Use of serum-free media for peripheral blood mononuclear cell culture and the impact on T and B cell readouts

Nanomaterials and security in occupational and forensic medicine: insights from nanotoxicology

Haematological parameters and biochemical indices of African catfish (Clarias gariepinus) exposed to glyphosate-based herbicide (Force up®) for 96 hours

Dechorionated zebrafish embryos improve evaluation of nanotoxicity

A multimodal in vitro approach to assess the safety of oral care products using 2D and 3D cellular models

Editorial: Women in environmental toxicology