Abstract
Manufactured nanomaterials (NMs) are increasingly used in a wide range of industrial applications leading to a constant increase in the market size of nano-enabled products. The increased production and use of NMs are raising concerns among different stakeholder groups with regard to their effects on human and environmental health. Currently, nanosafety hazard assessment is still widely performed using in vivo (animal) models, however the development of robust and regulatory relevant strategies is required to prioritize and/or reduce animal testing. An adverse outcome pathway (AOP) is a structured representation of biological events that start from a molecular initiating event (MIE) leading to an adverse outcome (AO) through a series of key events (KEs). The AOP framework offers great advancement to risk assessment and regulatory safety assessments. While AOPs for chemicals have been more frequently reported, the AOP collection for NMs is limited. By using existing AOPs, we aimed to generate simple and testable strategies to predict if a given NM has the potential to induce a MIE leading to an AO through a series of KEs. Firstly, we identified potential MIEs or initial KEs reported for NMs in the literature. Then, we searched the identified MIE or initial KEs as keywords in the AOP-Wiki to find associated AOPs. Finally, using two case studies, we demonstrate how in vitro strategies can be used to test the identified MIE/KEs.
Highlights
These Performance Standards (PS) include the following sets of information: (i) Essential Test Method Components that serve to evaluate the structural, mechanistic and procedural similarity of a new similar or modified proposed test method, (ii) a list of 20 Reference Chemicals to be used for validating new or modified test methods and (iii) defined target values of reproducibility and predictive capacity that need to be met by proposed test methods in order to be considered similar to the validated reference methods
The containment properties of the RECONSTRUCTED HUMAN EPIDERMIS (RhE) model should prevent the passage of test chemical around the stratum corneum to the viable tissue, which would lead to poor modelling of skin exposure
The RhE model should only be used if the developer/supplier demonstrates that each batch of the RhE model used meets defined production release criteria, amongst which those for viability, barrier function and morphology are the most relevant
Summary
PERFORMANCE STANDARDS FOR THE ASSESSMENT OF PROPOSED SIMILAR OR MODIFIED IN VITRO RECONSTRUCTED HUMAN EPIDERMIS (RhE) TEST METHODS FOR SKIN IRRITATION TESTING AS DESCRIBED IN TG 439. Complete document available on OLIS in its original format This document and any map included are without prejudice to the status of or sovereignty over any territory, to the delimitation of international frontiers and boundaries and to the name of any territory, city or area
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