On the relevance of genomic approaches to hazard assessment of functionalized nanomaterials in the NAM framework.

New approach methodologies (NAMs) are changing the ways by which alternative toxicology, in vitro mainly, is approaching the evaluation of hazard of novel materials or compounds. Engineered nanoparticles (NPs) are a typical class of compounds where NAMs found an important area of application. The number of novel NPs and NPs-based products are increasing at a pace that classical in vivo toxicology has difficult to keep. NAMs on the other hand are faster and may provide more human relevant outcomes. According to the Safe and Sustainable by design (SSbD) framework, we report here the comparison of silver NPs (AgNPs) with different functionalization (naked, with curcumin or with hydroxyethyl cellulose). A lung in vitro model (A549 cells with THP-1-derived macrophages) is exposed with a NAM at the air-liquid interface (ALI). The outcomes are explored with a genomic approach followed by RT-PCR. The results show the relevance of combining two de facto NAM to obtain data relevant to human expected exposure and to mine the plethora of hazard information in vitro model can provide. The combination of these approaches should be considered as a reference approach also to pave the road for regulatory acceptance.