Monotonic dose-response testing for Nanomaterial toxicity
NanoInformaTIX
NanoInformaTIX is a European project which aims to develop a web-based Sustainable Nanoinformatics Framework (SNF) platform to predict nanomaterial toxicity. The main objectives of the project comprise, in first instance, the development of models for Engineered NanoMaterial (ENM) release, exposure, and dose-response relationship for (eco)-toxicity; and in a second step the validation of these models. The framework makes use of new and existing data on the physico-chemical, toxicological and ecotoxicological properties of ENM.
An important part of the project focusses on the development of a strategy to calculate in vivo exposure doses based on in vitro data. Within this part the project, a particular task is dedicated to the detection of dose-response monotone relationships, dose-response modelling and risk calculation.
Development of NMTox
This task started by compiling all data from the NanoInformaTIX database in order to create an overview of the type and completeness of data available for selected endpoints and/or ENM types. The R-package NMTOX was developed for data exploration and to study dose-response trends based on these datasets. Within the NanoInformaTIX project, this will enable to identify in vivo and in vitro toxicity endpoints.
Appropriate datasets for in vitro toxicity endpoints can be identified to obtain in vitro toxic doses for specific endpoints (e.g. cytotoxicity, genotoxicity micronucleus endpoint or comet assay) and nanomaterials. This can be done via the Shiny app that allows the fitting of several dose-response models to data and to derive a weighted average toxic dose at the desired level (Effective Concentration e.g. EC10, EC50, …). The Shiny App is based on the NMTox R package and can be used to produce the data analysis output without having any background with R.
Methodology and software development were performed by Thomas More University of Applied Sciences and the University of Hasselt.
Future applications
Overall, the NMTox R package can be used to identify significant trends in the dose-response relationship of nanomaterial toxicity. The NMTox Shiny app can be used for exploratory data analysis and inference for monotone trends on Nanoinformatics data.
NMTOx is a versatile tool that will help in the sustainable production of ENM while reducing animal experimentation, using a safe by design approach and classifying ENM for risk assessment. The NanoInformaTIX platform will serve for different stakeholders such as industry, regulators, consumers and researchers.
Contact: Geert Verheyen - Thomas More University of Applied Sciences
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