Development of a Quasi-QSAR 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-QSARs to estimate the Hill coefficient ( n 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 quasi-SMILES and correlated to experimentally derived values of n H . Monte Carlo optimization was used to model the set of n H values and the model was trained on the basis of reported dose-response relationships of 60 datasets (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 modelled response data. The technique was employed to predict the dose-response relationships of 15 additional datasets (n = 72 individual observations) not included in model development of 7 metal-based nanomaterials from 10 literature reports, with an average error of 3.5 %. Combining the model output with either the median effective concentration (EC50 ) value or any other known effect level as obtained from experimental data, allows the prediction of full dose-response curves of Daphnia magna immobilization. This model is an accurate screening tool that allows to determine the shape and slope of dose-response curves, thereby greatly reducing the experimental efforts in case of novel advanced metal-based nanomaterials, or to predict responses in altered exposure media. This screening model is compliant to the 3Rs (Replacement, Reduction and Refinement) principles which is embraced by the scientific and regulatory communities dealing with Nanosafety. This article is protected by copyright. All rights reserved.© 2022 The Authors. Environmental Toxicology and Chemistry published by Wiley Periodicals LLC on behalf of SETAC