The application of existing genotoxicity methodologies for grouping of nanomaterials: towards an integrated approach to testing and assessment

Abstract

The incorporation of nanomaterials (NMs) in consumer products has proven to be highly valuable in many sectors. Unfortunately, however, the same nano specific physicochemical properties, which make these material attractive, might also contribute to hazards for people exposed to these materials. The physicochemical properties of NMs will impact their interaction with biological surroundings and influence their fate and their potential adverse effects such as genotoxicity. Due to the large and expanding number of NMs produced, their availability in different nanoforms (NFs) and their utilization in various formats, it is impossible for risk assessment to be conducted on an individual NF basis. Alternative methods, such as grouping are needed for streamlining hazard assessment. The GRACIOUS Framework provides a logical and science evidenced approach to group similar NFs, allowing read-across of hazard information from source NFs (or non-NFs) with adequate hazard data to target NFs that lack such data. Here, we propose a simple three-tiered testing strategy to gather evidence to determine whether different NFs are sufficiently similar with respect to their potential to induce genotoxicity, in order to be grouped. The tiered testing strategy includes simple in vitro models as well as a number of alternative more complex multi-cellular in vitro models to allow for a better understanding of secondary NM-induced DNA damage, something that has been more appropriate in vivo until recently.

DNA Oxidative Damage as a Sensitive Genetic Endpoint to Detect the Genotoxicity Induced by Titanium Dioxide Nanoparticles

“…The most suitable cell lines for the evaluation of the genotoxicity in nanomaterials have not yet been determined. In addition, a very important knowledge gap in nanogenotoxicity research is that there could be developed in vitro test methods suitable for detecting secondary genotoxicity [ 36 ]. This study showed that in vitro studies could detect the secondary genotoxicity in nanomaterials, especially those mediated by oxidative stress.…”

Toxicity and Mechanisms of Engineered Nanoparticles in Animals with Established Allergic Asthma

“… 2 Additionally, possible health hazards of NPs have been manifested by effects on immune defense, T-helper Th1/Th2 balance, and non-immunological aspects such as oxidative stress, apoptosis, autophagy, genotoxicity, and carcinogenesis. 9 , 13 The skin, respiratory and gastrointestinal tracts of the body are connected to the external environment and are therefore the main exposure sites for NPs. 5 Furthermore, NPs have the potential to translocate to different distal organs.…”

How to formulate hypotheses and IATA to support grouping and read-across of nanoforms

“…When the initial inhalation hypothesis was developed, insufficient information to support hypothesis generation for genotoxicity of NFs was identified. However, in order to future-proof the Framework, Verdon et al (2022) have generated a genotoxicity tiered testing strategy that can be added into the existing IATA to address this gap, should future hypotheses require consideration of genotoxicity (Figure S1 6 ).…”