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By applying “New Approach Methodologies (NAMs)” based on innovative technologies such as computer modeling, high throughput testing, omics, and sophisticated cell cultures, the use of experimental animals in the life sciences can be reduced or sometimes even completely avoided. Stimulating NAMs may benefit from a bottom-up approach, i.e., local initiatives mapping the available NAMs and promoting their use. An example of such an initiative in Belgium is the RE-Place project, which collects the available NAMs in one central database, and links this knowledge with the names of experts and research centers. To this extent, a template was created to collect the information of interest in a fast and consistent manner. Based on this template, a web-based application was developed to facilitate the entry of information, which was evaluated in a pilot study by experts in the field of NAMs. After integration of their feedback, a revised version of the RE-Place online tool was launched to the public. Aspects such as user-friendliness, quality of submitted information, protection of personal data and Intellectual Property (IP) rights were all considered in the development process. Hurdles like incentives for collaboration were also taken into account. Information submitted with the online tool is directly integrated in the RE-Place open access database. By consulting the database, scientists from various disciplines can easily identify the different types of NAMs and the experts using them in Belgium. As such, the RE-Place database contributes to building trust in the use of NAMs and stimulating their use and regulatory uptake.

Due to the complexity and variability of textile wastewater composition, a constant search for new treatment strategies that are efficient, eco-friendly, and cost-effective is mandatory. In the present study, the efficiency of coagulation-flocculation using biocoagulants derived from cactus Opuntia ficus indica and eggplant Solanum melongena to remove toxic compounds from Tunisian textile wastewater samples was evaluated by combining assays to investigate physicochemical properties and in vitro (geno)toxicity with analytical chemistry. Both natural coagulants could significantly improve the physicochemical properties of the textile wastewater samples compared to the traditionally used chemical coagulant. The highest rate of decolorization was achieved after treatment with the cactus-derived coagulant. The analytical study revealed the presence of only crystal violet dye (CV) in only one sample. Both natural coagulants were able to remove CV, which may (partially) explain the decolorization of the treated samples. Only one untreated textile effluent induced a genotoxic response in the VITOTOX ® assay. The genotoxic effect was not linked to the presence of CV and was no longer observed after treatment with each of the natural coagulants, suggesting the effectiveness of the remediation treatments to remove potentially genotoxic compound(s). However, in the other genotoxicity tests, no biologically relevant effects were observed for any of the tested samples. In conclusion, although the physicochemical data indicate that the use of natural coagulants (cactus and eggplant) could be an interesting alternative treatment process to the chemical coagulant for detoxifying textile effluents, these results were only partially supported by the toxicological and analytical data.

Mycotoxins are naturally occurring secondary metabolites produced by specific fungal strains. They can cause adverse effects, posing a serious health threat to both humans and livestock. Focusing on several mycotoxins, this study first aimed at optimizing and validating an ultra-high liquid chromatography-tandem mass spectrometry quantification method. This method was then applied to evaluate the production of the targeted mycotoxins in maize cultivated in the presence of Aspergillus spp., Fusarium spp., and Alternaria spp. The limits of detection of the analytical method for the different mycotoxins ranged between 0.5 and 200 μg kg−1, while the limits of quantification were between 1 and 400 μg kg−1. The linearities of the calibration curves were evaluated, with calculated R2 values above 0.99. The mean recoveries fell within the acceptable range of 74.0–106.0%, the repeatability was not higher than 14.4% RSD, and the highest intra-laboratory reproducibility was 16.2% RSD. The expanded measurement uncertainties ranged between 4.0% and 54.7%. Several fungal strains cultivated on maize grains were demonstrated to produce the targeted toxins, with production at µg kg−1 to mg kg−1 levels for aflatoxins and up to g kg−1 levels for fumonisins, zearalenone, and alternariol.

Although the value of the regulatory accepted batteries for in vitro genotoxicity testing is recognized, they result in a high number of false positives. This has a major impact on society and industries developing novel compounds for pharmaceutical, chemical, and consumer products, as afflicted compounds have to be (prematurely) abandoned or further tested on animals. Using the metabolically competent human HepaRG™ cell line and toxicogenomics approaches, we have developed an upgraded, innovative, and proprietary gene classifier. This gene classifier is based on transcriptomic changes induced by 12 genotoxic and 12 non-genotoxic reference compounds tested at sub-cytotoxic concentrations, i.e., IC10 concentrations as determined by the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay. The resulting gene classifier was translated into an easy-to-handle qPCR array that, as shown by pathway analysis, covers several different cellular processes related to genotoxicity. To further assess the predictivity of the tool, a set of 5 known positive and 5 known negative test compounds for genotoxicity was evaluated. In addition, 2 compounds with debatable genotoxicity data were tested to explore how the qPCR array would classify these. With an accuracy of 100%, when equivocal results were considered positive, the results showed that combining HepaRG™ cells with a genotoxin-specific qPCR array can improve (geno)toxicological hazard assessment. In addition, the developed qPCR array was able to provide additional information on compounds for which so far debatable genotoxicity data are available. The results indicate that the new in vitro tool can improve human safety assessment of chemicals in general by basing predictions on mechanistic toxicogenomics information.

Cymbopogon giganteus Chiov. (Poaceae) is a medicinal plant used to treat various diseases in traditional medicine in several African countries. The present study aims to evaluate the oral and inhalation toxicity as well as the mutagenic effects of the essential oil of Cymbopogon giganteus leaves (EOCG) from a sample collected in Benin. Mutagenic potential was assessed by the Ames test using Salmonella typhimurium strains TA98 and TA100. Oral acute toxicity was carried out by administration of a single dose of 2000 mg/kg b.w. to Wistar rats while oral subacute toxicity was assessed by daily administration of 50 and 500 mg/kg of EOCG for 28 days. Finally, inhalation toxicity was assessed by administration of a single dose of 0.125%, 0.5%, 2% or 5% v/v of EOCG emulsions in 0.05% v/v lecithin solution in sterile water for the first experiment, and in a second one by administration of single dose of 0.125% or 0.5% v/v. A broncho-alveolar lavage was performed after 3 h or 24 h, respectively. The results show that EOCG is not mutagenic on Salmonella typhimurium strains at the highest concentration tested (200 μg/plate). In the acute oral toxicity study, EOCG induce neither mortality nor toxicity, showing that the LD50 is greater than 2000 mg/kg. The subacute oral toxicity study at both doses did not show any significant difference in body weight, relative organ weight, hematological and/or biochemical parameters or histopathology as compared to the control group. EOCG induced mortality and inflammation in lungs 3 h after administration of a single dose of 5% or 2% v/v. Single doses of 0.125% or 0.5% v/v did not induce inflammation, cell recruitment nor cytotoxicity in lungs 3 h or 24 h after administration, suggesting safety at these concentrations. This first report on the in vivo toxicity will be useful to guide safe uses of EOCG.

Chemical risk assessment has historically focused on single compounds, neglecting the implications of combined exposures. To bridge this gap, several methodologies, such as concentration addition (CA) and independent action (IA), have been developed. However, a systematic, consistent, and integrated approach across various legislative frameworks is still lacking. The assessment of combined effects of genotoxicants is even more challenging, as genotoxicity data are typically evaluated qualitatively, without considering the effect size. This study aimed to develop a quantitative approach for evaluating the combined effects of genotoxic compounds with both similar and dissimilar modes of action (MoA), based on the benchmark concentration (BMC) principle. A proof-of-concept study was conducted using the in vitro micronucleus (MNvit) test to examine two types of binary mixtures: ethyl methanesulfonate (EMS) and methyl methanesulfonate (MMS), which share similar MoA, and MMS and etoposide (ETP), which have dissimilar MoA. The methodology involved collecting data for individual compounds, calculating BMC values, composing mixtures with different ratios and inducing various effect levels, testing these mixtures, and comparing the experimental results with the modelled data to verify additivity. The findings indicated that for both mixtures, the experimental responses aligned with the predicted additive effects, supporting the validity of the additivity principle. This study highlights the potential of an optimized BMC-based approach as a robust framework for testing chemical mixtures. It should be adopted in future studies to evaluate a wider range of genotoxic compounds, offering a more comprehensive and quantitative strategy for assessing combined chemical exposures.

In this study, hazardous wastes including fluff, dust, and scrubbing sludge were sampled in 2019 from two metal shredding facilities located in Wallonia, Belgium. To assess the extent of the contamination, a global approach combining chemical and biological techniques was used, to better reflect the risks to health and the environment. The samples investigated induced significant in vitro aryl hydrocarbon receptor (AhR) agonistic bioactivities and estrogenic receptor (ERα) (ant)agonistic bioactivities in the respective CALUX (chemical activated luciferase gene expression) bioassays. The mutagenicity of the samples was investigated with the bacterial reverse gene mutation test using the Salmonella typhimurium TA98 and TA100 strains. Except for the sludge sample (site 3), all samples induced a mutagenic response in the TA98 strain (± S9 metabolic fraction) whereas in the TA100 strain (+ S9 metabolic fraction), only the sludge sample (site 2) showed a clear mutagenic effect. The in vivo toxicity/teratogenicity of the shredder wastes was further evaluated with zebrafish embryos. Except for the dust sample (site 2), all samples were found to be teratogenic as they returned teratogenic indexes (TIs) > 1. The high levels of contamination, the mutagenicity, and the teratogenicity of these shredder wastes raise significant concerns about their potential negative impacts on both human health and environment.

Enniatins (ENNs) and beauvericin (BEA) are cyclic hexadepsipeptide fungal metabolites which have demonstrated antibiotic, antimycotic, and insecticidal activities. The substantial toxic potentials of these mycotoxins are associated with their ionophoric molecular properties and relatively high lipophilicities. ENNs occur extensively in grain and grain-derived products and are considered a food safety issue by the European Food Safety Authority (EFSA). The tolerable daily intake and maximum levels for ENNs in humans and animals remain unestablished due to key toxicological and toxicokinetic data gaps, preventing full risk assessment. Aiming to find critical data gaps impeding hazard characterization and risk evaluation, this review presents a comprehensive summary of the existing information from in vitro and in vivo studies on toxicokinetic characteristics and cytotoxic, genotoxic, immunotoxic, endocrine, reproductive and developmental effects of the most prevalent ENN analogues (ENN A, A1, B, B1) and BEA. The missing information identified showed that additional studies on ENNs and BEA have to be performed before sufficient data for an in-depth hazard characterisation of these mycotoxins become available.