In-vitro Toxicity Assessment

A scheme for in-vitro cytotoxicity testing is defined by the international and European 

1992) and EN 30993-5 (Standards 1994) which makes available a battery of tests, the choice of which depends on the nature of the sample to be evaluated, the potential site of use, and the nature of the use. 

The numerous methods applied and the end-points measured in cytotoxicity determination can be performed by either qualitative or quantitative means. The following examples and results on the cytotoxicity of metals and implantable alloys correspond to 8.5.1.b Quantitative evaluation of the above-mentioned standards  

Measure cell death, inhibition of cell growth, cell proliferation or colony formation. The number of cells, amount of protein, release of enzyme, release of vital dye, reduction of vital dye or other measurable parameters may he quantified by objective means. The objective measure and response is recorded in the test report. 

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Boelsterli, U.A., Bouis, P., Brouillard, J.F. and Donatsch, P. (1988). In vitro toxicity assessment of cyclosporin A and its analogs in a primary rat hepatocyte culture model. Toxicol. Appl. Pharmacol. 96 212-221. 

Parameters Affecting the NM Fate and Biological Activity During In Vitro Toxicity Assessment... 

Nendza, M. and Seydel, J. K. (1990) Application of bacterial growth kinetics to in vitro toxicity assessment of substituted phenols and anilines. Ecotoxicol. Environ. Saf, 19, 228-41. 

Gad, S.C. (1992). Industrial application for in vitro toxicity testing methods A tier testing strategy for product safety assessment. In In Vitro Toxicity Testing (Frazier, J., Ed.). Marcel Dekker, New York, pp. 253-279. 

For in vitro toxicity studies and assessment of the barrier function, drug transport, cell physiology, and metabolism as well as the development of delivery systems, cell culture models provide powerful systems for scientific research. As the corneal epithelium is the main barrier for ocular penetration, various corneal epithelial cell cultures were established besides the corneal constructs that mimic the whole cornea and serve as reductionist models for the ocular barrier. In general, two types of cell culture models are available primary cell cultures and immortalized, continuous cell lines. 

In vivo and in vitro toxicity testing methods are used to assess potential adverse health effects of chemical contaminants. These methods have been used to confirm many suspected substances as toxic and carcinogenic. To date, only a small fraction of the organic makeup of most drinking waters has been elucidated and tested. Broad spectrum... 

Trohalaki, S., Zellmer, R. J., Pachter, R., Hussain, S. M., and Frazier, J. M., Risk assessment of high-energy chemicals by in vitro toxicity screening and quantitative structure-activity relationships, Toxicol. Sci. 68, 498-507 (2002). 

As in the case of chemical or pharmaceutical substances, the results from in vitro toxicity testing of NMs are dependent upon many factors, such as the cell types used, exposure time, dosing regimen, and exposure conditions. However, what makes toxicology of NMs so complex as compared to chemical products is the large number of physicochemical properties that are essential to know for proper toxicity assessment. The toxicity mechanisms are multiple and depend strongly on the characteristics of the studied NMs and the conditions of the test. Several aspects may affect the... 

Blaauboer BJ (2008) The contribution of in vitro toxicity data in hazard and risk assessment current limitations and future perspectives. Toxicol Lett 180(2) 81-84... 

Williams PD, Rush GF. An evaluation of in vitro models for assessing nephrotoxicity. In In vitro toxicity testing. Frazier JM (editor). Marcel Dekker Inc, New York/Base /Flong Kong 1992 p. 85-110. 

New biomarker discovery from such studies can lead to early detection of deleterious effects. In a more recent study, researchers validated toxicological protein markers from an in vivo system (rat liver) as well as from an in vitro system (human HepG2 cell line) [86]. They reported a total of 11 protein markers with reactivity toward multiple toxic compounds and no reactivity toward nontoxic compounds. An important conclusion from this work is that cells in culture can be used as an in vitro toxicity testing system to assess hepatotoxicity. However, in the future, a much more extensive study may be required to identify a larger group of toxicology markers to detect more diverse types of toxic reactions. 

In this chapter, we first divide NIR NMs into five species carbon-based materials, quantum dots (QDs), noble metal-based nanoparticles (NPs), upconversion nanoparticles (UCNPs), and narrow-bandgap semiconductors. Then, we focus primarily on the progress of their toxicity studies in the past several years, discuss in detail how the biophysicochemical properties of NIR NMs influence their in vitro and in vivo toxicity, present a broad overview of the available in vitro and in vivo toxicity assessments of NIR NMs, and finally frame the future outlook for NIR NMs by highlighting areas of exceptional promise and challenges. Our emphasis here is mainly on discussion that could offer future opportunities to design and create NIR NMs with good biocompatibility as well as excellent functionalities, rather than attempting to provide a complete historical survey. 

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