Received: 16 October 2018 | Revised: 9 February 2019 | Accepted: 15 March 2019 DOI: 10.1002/jbt.22335 REVIEW Rational approaches for toxicological assessments of nanobiomaterials Shalabh Pandey | Awanish Mishra Department of Pharmacology and Toxicology, National Institute of Pharmaceutical Education and Research (NIPER‐R), Lucknow, Uttar Pradesh, India Correspondence Awanish Mishra, Department of Pharmacology and Toxicology, National Institute of Pharmaceutical Education and Research (NIPER‐R), Bijnor‐Sisendi Road, Sarojini Nagar, Near CRPF Base Camp, Lucknow‐226002, Uttar Pradesh, India. Email: Awanish.mishra@niperraebareli.edu.in; awanish1985@gmail.com Abstract The nanobiomaterials display unique and distinguished usefulness in day‐to‐day life. The application of nanobiomaterials is being utilized in several segments, including semiconductor industries, cosmetics, and medicines. Alongside their usefulness these nanobiomaterials have potential toxicity which may limit it's further use. As there is sparse information on toxicological facets of nanomaterials available, a proactive approach for evaluation of potential risk of nanobiomaterials should be exercised. This review explains the potential mechanism of nanobio- materials toxicity and rational approaches for selection of protocols to study toxicity of nanobiomaterials. KEYWORDS acute toxicity, chronic toxicity, cytotoxicity, nanobiomaterials, oxidative stress 1 | INTRODUCTION Since the emergence of nanotechnology, the development of new nanobiomaterials (NM) has been continuously increased. These are potentially valuable in terms of their applications which range from healthcare products to engineering NM. [1] NM has been described as materials having size (at least one dimension) between 1 and 1000 nm. [2] Generally three types of NM have been reported, combustion derived NM (diesel), engineered NM (gold/silver nano- particles, etc) and naturally occurring NM (volcanic eruptions). Although there is abundance of natural NM in the environment, but in last two decades, there is an increased production and the application of NM in various areas like, medicine, food additives and preservatives, cosmetics, electronics, paints, water treatment, etc. The nanoencapsulated dosage form has proven their utility in the improved solubility, stability, and bioavailability of drugs. NM‐ mediated drug delivery has proven their efficacy in the management of various neurodegenerative diseases like Alzheimer's disease and Parkinson's disease. NM is also being explored as therapeutic and diagnostic agents, waste management, and reduction of industrial contaminants. The potential applications of NM are limitless and lucrative, which serves as driving force for rapid rush for pushing these application to the market. The manufacturing, use and disposal of the NM lead to their contamination to air, soil, and water. The indiscriminate use of these NMs without knowing its toxicological facets might pose significant risk for environment, humans, and wildlife. There is limited data available for the toxicity of NM and at present no specific regulations have been developed for the NM. The potential exposure routes for NM are inhalation, ingestion, and dermal penetration (Figure 1). However their physicochemical properties (like, shape, size, surface area, and surface charge) are also the determinant factor for their toxicity. As the size of NM and surface to volume ratio are less, as compared to their larger counterparts, they possess unique biological properties. Even the inert materials become highly active at nanodimensions like, gold, silver, etc. The most striking behavior of J Biochem Mol Toxicol. 2019;e22335. wileyonlinelibrary.com/journal/jbt © 2019 Wiley Periodicals, Inc. | 1 of 9 https://doi.org/10.1002/jbt.22335 Abbreviations: ATF6, activating transcription factor 6; ATP, adenosine triphosphate; BrdU, bromodeoxyuridine; CAT, catalase; ER, endoplasmic reticulum; FDA, Food and Drug Administration; GSH, glutathione; GSSG, oxidised glutathione; ICH, The International Conference on Harmonisation of Technical Requirements for Registration of Pharmaceuticals for Human Use; IL, interleukin; IRE1, inositol‐requiring enzyme 1; LDH, lactate dehydrogenase; MTS, 3‐(4,5‐dimethylthiazol‐2‐yl)‐5‐(3‐carboxymethoxyphenyl)‐2‐(4‐sulfophenyl)‐2H‐tetrazolium; MTT, 3‐(4‐5‐ dimethylthiazol‐2‐yl)‐2,5‐diphenyltetrazolium; NF‐κB, nuclear factor κ‐light‐chain‐enhancer of activated B cells; NM, nanobiomaterial; Nrf‐2, nuclear factor erythroid 2–related factor 2; OECD, Organisation for Economic Co‐operation and Development; PASS, prediction activity spectra for substances; PERK, protein kinase‐R like ER kinase; PI, propidium iodide; QSAR, quantitative structure‐activity relationship; RNS, reactive nitrogen species; ROS, reactive oxygen species; SOD, superoxide dismutase; TNF‐α, tumor necrosis factor α; WST‐1, water soluble tetrazolium salts; XTT, 2,3‐bis‐(2‐methoxy‐4‐nitro‐5‐sulfophenyl)‐2H‐tetrazolium‐5‐carboxanilide.