Development of a quasi-quantitative structure-activity relationship model for prediction of the immobilization response of Daphnia magna exposed to metal-based nanomaterials

The conventional Hill equation model is suitable to fit dose-response data obtained from performing (eco)toxicity assays. Models based on quasi-quantitative structure-activity relationships (QSARs) to estimate the Hill coefficient ( n H ) ${n}_{{\rm{H}}})$ were developed with the aim of predicting the response of the invertebrate species Daphnia magna to exposure to metal-based nanomaterials. Descriptors representing the pristine properties of nanoparticles and media conditions were coded to a quasi-simplified molecular input line entry system and correlated to experimentally derived values of n H ${n}_{{\rm{H}}}$. Monte Carlo optimization was used to model the set of n H ${n}_{{\rm{H}}}$ values, and the model was trained on the basis of reported dose-response relationships of 60 data sets (n = 367 individual response observations) of 11 metal-based nanomaterials as obtained from 20 literature reports. The model simulates the training data well, with only 2.3% deviation between experimental and modeled response data. The technique was employed to predict the dose-response relationships of 15 additional data sets (n = 72 individual observations) not included in model development of seven metal-based nanomaterials from 10 literature reports, with an average error of 3.5%. Combining the model output with either the median effective concentration value or any other known effect level as obtained from experimental data allows the prediction of full dose-response curves of D. magna immobilization. This model is an accurate screening tool that allows the determination of the shape and slope of dose-response curves, thereby greatly reducing experimental effort in case of novel advanced metal-based nanomaterials or the prediction of responses in altered exposure media. This screening model is compliant with the 3Rs (replacement, reduction, and refinement) principle, which is embraced by the scientific and regulatory communities dealing with nano-safety. Environ Toxicol Chem 2022;00:1-12. (c) 2022 The Authors. Environmental Toxicology and Chemistry published by Wiley Periodicals LLC on behalf of SETAC.Environmental Biolog

Taxon-toxicity study of fish to typical transition metals: most sensitive species are edible fish

Transition metals are widespread in aquatic environments and can be harmful when concentrations exceed thresholds. Especially for fish, an important component of the human diet, low concentrations of transition metals will directly affect their well-being. Different taxa are protected by unified water quality criteria (WQC) thresholds, which rarely consider the ecological status and economic value of different species. There is therefore an urgent need to study taxon-specific sensitivity. The present study established the species sensitivity distributions of nine typical transition metals (Cr, Mn, Fe, Ni, Cu, Zn, Ag, Cd and Hg) for protecting freshwater and seawater fish based on non-parametric kernel density estimation methods, and then derived their acute and chronic HC5-values. The results showed that Ag and Hg have the highest acute toxic potency to fish in freshwater as well as seawater. Compared with marine fish, freshwater fish were more tolerant to acute exposure to Cr, Fe, Ni and Zn, whilst being more sensitive to Ag and Cd. Moreover, edible fish are more sensitive than other fish to these metals in both freshwater and seawater, encouraging more protection of economically valuable fish that may potentially affect human health. The study provides a strong reference for future research on taxon-specific WQC for transition metals.Environmental Biolog

Consideration of the bioavailability of metal/metalloid species in freshwaters: experiences regarding the implementation of biotic ligand model-based approaches in risk assessment frameworks

After the scientific development of Biotic Ligand Models (BLMs) in recent decades these models are now considered suitable for implementation in regulatory risk assessment of metals in freshwater bodies. The approach has been developed over several years and has been described in many peer-reviewed publications. The original complex BLMs have been applied in prospective risk assessment reports for metals and metal compounds and are also recommended as suitable concepts for the evaluation of monitoring data in the context of the European Water Framework Directive. Currently, several user-friendly BLM-based bioavailability software tools are available for assessing the aquatic toxicity of a limited number of metals (mainly copper, nickel, and zinc). These tools need only a basic set of water parameters as input (e.g., pH, hardness, dissolved organic matter and dissolved metal concentration). Such tools seem appropriate to foster the implementation in routine water quality assessments. This work aims to review the existing bioavailability-based regulatory approaches and the application of available BLM-based bioavailability tools for this purpose. Advantages and possible drawbacks of these tools (e.g., feasibility, boundaries of validity) are discussed, and recommendations for further implementation are given

Systems toxicology to advance human and environmental hazard assessment : A roadmap for advanced materials

Ideally, a Systems Toxicology (ST) approach is aimed at by (eco)toxicologists, i.e. a multidisciplinary area incorporating classical toxicological concepts with omics technologies, and the understanding of this through computational data sciences, chemistry, mathematics, and physics modelling. As outlined in sev-eral public reports (e.g. from ECHA-European Chemical Agency and EFSA-European Food Safety Authority), the way forward in the coming years in Europe is to integrate New Approach Methodologies (NAMs) (in-cluding omics technologies) into hazard and hence risk assessment (RA). Adverse Outcome Pathways (AOPs) describe a sequence of events in response to stress, from the molecular initiating event until an adverse outcome, which is relevant to RA or regulatory decision-making. AOPs are one of the facilitators to integrate mechanistic data into RA, but it is urgent to increase the inclusion of the vast mechanistic knowledge available, especially for the RA of novel smart and advanced materials (AdMa) with multi-functional characteristics. There are still many challenges to the routine usage of NAMs, e.g. omics-based information. Here, we summarise the current state of the art of ST, the benefits of human and environ-mental health cross knowledge and the available methods and output. The importance of this area has been highlighted for many years but is even more pressing in the context of AdMa. Furthermore, we outline the challenges and suggest recommendations for future implementation.(c) 2022 The Author(s). Published by Elsevier Ltd. This is an open access article under the CC BY license (http://creativecommons.org/licenses/by/4.0/).Peer reviewe

Exploring uptake and biodistribution of polystyrene (nano)particles in zebrafish embryos at different developmental stages.

In ecotoxicology, it is continuously questioned whether (nano)particle exposure results in particle uptake and subsequent biodistribution or if particles adsorb to the epithelial layer only. To contribute to answering this question, we investigated different uptake routes in zebrafish embryos and how they affect particle uptake into organs and within whole organisms. This is addressed by exposing three different life stages of the zebrafish embryo in order to cover the following exposure routes: via chorion and dermal exposure; dermal exposure; oral and dermal exposure. How different nanoparticle sizes affect uptake routes was assessed by using polystyrene particles of 25, 50, 250 and 700nm. In our experimental study, we showed that particle uptake in biota is restricted to oral exposure, whereas the dermal route resulted in adsorption to the epidermis and gills only. Ingestion followed by biodistribution was observed for the tested particles of 25 and 50nm. The particles spread through the body and eventually accumulated in specific organs and tissues such as the eyes. Particles larger than 50nm were predominantly adsorbed onto the intestinal tract and outer epidermis of zebrafish embryos. Embryos exposed to particles via both epidermis and intestine showed highest uptake and eventually accumulated particles in the eye, whereas uptake of particles via the chorion and epidermis resulted in marginal uptake. Organ uptake and internal distribution should be monitored more closely to provide more in depth information of the toxicity of particles