Computational models for the assessment of manufactured nanomaterials: Development of model reporting standards and mapping of the model landscape

L Lamon,D Asturiol,A Vilchez,R Ruperez-Illescas,J Cabellos,A Richarz,A Worth

doi:10.1016/j.comtox.2018.12.002

L Lamon, D Asturiol + Show 5 more

Open Access

https://doi.org/10.1016/j.comtox.2018.12.002

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Abstract

Different types of computational models have been developed for predicting the biokinetics, environmental fate, exposure levels and toxicological effects of chemicals and manufactured nanomaterials (MNs). However, these models are not described in a consistent manner in the scientific literature, which is one of the barriers to their broader use and acceptance, especially for regulatory purposes. Quantitative structure-activity relationships (QSARs) are in silico models based on the assumption that the activity of a substance is related to its chemical structure. These models can be used to provide information on (eco)toxicological effects in hazard assessment. In an environmental risk assessment, environmental exposure models can be used to estimate the predicted environmental concentration (PEC). In addition, physiologically based kinetic (PBK) models can be used in various ways to support a human health risk assessment. In this paper, we first propose model reporting templates for systematically and transparently describing models that could potentially be used to support regulatory risk assessments of MNs, for example under the REACH regulation. The model reporting templates include (a) the adaptation of the QSAR Model Reporting Format (QMRF) to report models for MNs, and (b) the development of a model reporting template for PBK and environmental exposure models applicable to MNs. Second, we show the usefulness of these templates to report different models, resulting in an overview of the landscape of available computational models for MNs.

Highlights

Different types of mathematical models have been developed for quantification of exposure values or effect concentrations in the process of chemical risk assessment,1 and are potentially useful to support legislation, such as the EU regulation on the Registration, Evaluation, Authorisation and Restriction of Chemicals (REACH) [1].REACH addresses chemical substances and manufactured nanomaterials (MNs)
We described the “landscape” of available Quantitative structure-property relationships (QSPRs)/Quantitative structure-activity relationships (QSARs), physiologically based kinetic (PBK) and environmental exposure models, including the endpoints and MNs, the descriptors that are mostly considered in the models as well as the data sources used, the processes taken into consideration, and model limitations and assumptions
Modification of the QSAR Model Reporting Format (QMRF) to report MN models The QMRF is inspired to the OECD principles on QSAR model validation [3] and was proposed to give visibility to QSARs for regulatory applications

Summary

Introduction

REACH addresses chemical substances and manufactured nanomaterials (MNs). MNs are defined by the European Commission (EC) Recommendation on the Definition of a nanomaterial as materials containing particles, in an unbound state or as an aggregate or as an agglomerate and where, for 50% or more of the particles in the number size distribution, one or more external dimensions is in the size range 1–100 nm [2]. Quantitative structure-activity relationships (QSARs) are predictive models based on the assumption that the activity of a substance is related to its structure. Quantitative structure-property relationships (QSPRs) are conceptually the same as QSARs but they relate structure to physicochemical properties of chemicals

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