The nanosafety assessment of ENMs under a dermal exposure scenario: from key molecular events to in silico modeling tools

Abstract

While the use of engineered nanomaterials (ENMs) expanding to various applications and commercial products, public concerns about their potential hazards on exposure to humans are rising. Dermal absorption is the principal entry route for ENMs derived from various consumer products whose direct contact with skin are often inevitable. A rapid nanosafety assessment of ENMs at their early development stage is imperative. However, classical toxicological investigations of ENMs on a case-by-case basis are time-consuming and labor-intensive. In contrast, in silico nanosafety assessments based on computational toxicology is an area of growing interest as it has great potential to facilitate the rapid and sustainable development of ENMs and demonstrates continuous improvement with evolving computational techniques and databases. This review is committed to providing a systematic insight into ENM biokinetics and toxicity at nano-skin interfaces as well as a comprehensive view of current in silico modeling and simulation tools in predicting the fate and toxicity of ENMs under a dermal exposure scenario. Herein, we have thoroughly reviewed the key molecular events (dermal uptake and distribution, biotransformation at relevant interfaces, and nano-cell interactions) that may trigger or mitigate the toxic effects of ENMs. We have also demonstrated how in silico modeling tools, i.e., molecular dynamics, molecular docking, (quantitative) structure–activity relationship, and grouping and read-across, can be developed and employed to model or predict quantitative nanostructure (physicochemical properties)–toxicity relationships or to elucidate the toxicity-related molecular mechanisms. Finally, we have discussed the current challenges and future perspectives in this ground-breaking field.