Abstract

The extensive application of engineered nanomaterial (ENM) in various fields increases the possibilities of human exposure, thus imposing a huge risk of nanotoxicity. Hence, there is an urgent need for a detailed risk assessment of these ENMs in response to their toxicological profiling, predominantly in biomedical and biosensor settings. Numerous “toxico-omics” studies have been conducted on ENMs, however, a specific “risk assessment paradigm” dealing with the epigenetic modulations in humans owing to the exposure of these modern-day toxicants has not been defined yet. This review aims to address the critical aspects that are currently preventing the formation of a suitable risk assessment approach for/against ENM exposure and pointing out those researches, which may help to develop and implement effective guidance for nano-risk assessment. Literature relating to physicochemical characterization and toxicological behavior of ENMs were analyzed, and exposure assessment strategies were explored in order to extrapolate opportunities, challenges, and criticisms in the establishment of a baseline for the risk assessment paradigm of ENMs exposure. Various challenges, such as uncertainty in the relation of the physicochemical properties and ENM toxicity, the complexity of the dose-response relationships resulting in difficulty in its extrapolation and measurement of ENM exposure levels emerged as issues in the establishment of a traditional risk assessment. Such an appropriate risk assessment approach will provide adequate estimates of ENM exposure risks and will serve as a guideline for appropriate risk communication and management strategies aiming for the protection and the safety of humans.

Highlights

  • The environment surrounding us has a plethora of natural and manmade toxicants

  • engineered nanomaterial (ENM) have a broad spectrum of applications in various fields, such as in the fields of nanotheranostics and personalized medicine

  • These drugs significantly improve drug delivery to targeted cells as compared to the free diffusion of drug molecules. These drug delivery systems are advantageous over conventional chemotherapy, the substantial unidentified issues and potential cytotoxicity associated with the ENMs cannot be ignored (Oberdörster et al, 2005)

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Summary

INTRODUCTION

The environment surrounding us has a plethora of natural and manmade toxicants. These toxicants have gained access to almost every aspect of our life such as air, water, food, homes, workplaces, and belongings. In a study on workers (n = 24) with occupational exposure to multi-wall carbon nanotubes (MWCNT) and unexposed controls (n = 43) from the same workplace in the blood cells have shown changes in the DNA methylation (Ghosh et al, 2016, 2017) They observed significant methylation changes in DNMT1, ATM, SKI, and HDAC4 promoter CpGs of MWCNT exposed workers, which proves the fact that these occupational exposures may cause epigenetic changes which could produce deleterious effects in future, which may be inherited to the generation as well. The reduction in LINE-1 methylation due to CuO-NPs exposure caused enhanced Alu-1 and SINE repetitive elements transcription followed by TET1, TET2, and TET3 expression reduction in mouse macrophages (Lu et al, 2016b) Based on these studies, we can conclude that ENMs trigger de-regulation of genes involved in DNA methylation/demethylation reactions, as well as changes of genespecific methylation of tumor suppressor genes, inflammatory genes, and DNA repair genes, eventually leading to cancer growth and development. A study by Hauck et al reported alteration in gene expression by an unknown

Experimental setup and exposure time
16 HBE cells
CONCLUSION
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