In vitro toxicity studies

Table 7.1 S ummary of cytotoxicity assays used in in vitro toxicity studies on CNTs. 

Currently available information suggests that the shape of nanomaterials can affect their toxicity in two ways. First, the shape has an effect on the rate of its cellular uptake and second, it can affect the extent of nanomaterial aggregation, altering its cytotoxic properties. A recent in vitro toxicity study showed spherical nanomaterials to be more toxic than rods [120]. It was also shown to be more difficult for elliptical nanomaterials to penetrate the skin layer than spherical nanomaterials [121]. 

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 vitro toxicity studies are being used more commonly in drug safety evaluation as improved techniques are being developed. Their main uses at present are as a tool for screening compounds for toxicity to particular cell types and in studying cellular mechanisms for target organ toxicity. 

In vitro toxicity studies in the rat indicate that arsine toxicity is tissue-specific. Red blood cells are very susceptible to arsine toxicity, followed by the primary hepatocytes and renal cortical epithelial cells. In blood arsine is the only factor responsible for hemolysis whereas in other tissues it is only responsible for the early signs of toxicity. At later points the toxicity effect is a combination of many other factors, including formation of inorganic arsenicals and hemolysate (kidney toxicity). 

No in vitro toxicity studies have been reported. The mechanism of phosgene oxime toxicity is unknown and long-term exposure effects have not been determined. 

Since the BBB controls the exchanges between the blood and brain compartments modelling the BBB in vitro can also help to investigate the ability of compounds to cross the BBB. In this chapter, the plethora of in vitro BBB models that exist today is discussed and several methods needed to set up and use of these in vitro models in the framework of in vitro toxicity study is detailed. 

Wolfgang G, Vernetti L, MacDonald J (1994) Isolation and use of primary adrenocortical cells from guinea pigs, dogs and monkeys for in vitro toxicity studies. Toxicol Methods 4(3) 149-160... 

Hinderliter PM, Minard KR, Orr G, Chrisler WB, Thrall BD, Pounds JG, Teeguarden JG (2010) ISDD a computational model of particle sedimentation, diffusion and target cell dosimetry for in vitro toxicity studies. Part Fibre Toxicol 7(1) 36... 

Gunness P, Mueller D, Shevchenko V et al (2013) 3D organotypic cultures of human HepaRG cells a tool for in vitro toxicity studies. Toxicol Sci 33(l) 67-78... 

However, the most important driving force for performing in vitro toxicity studies is a scientific one if one wishes to study the toxicity mechanisms of action of a compound, it is no longer appropriate to rely on the apical endpoints for toxicity that are the commonly measured parameters in an animal study. A focus on these mechanisms, in relation to the events following the molecular initiating event, eventually leading to an adverse outcome gives... 

Experimental studies in tissue culture in vitro have also been performed for indium compounds. In vitro toxicity studies of InAs particles to hamster alveolar macrophages revealed slight damage to cells, but no necrotic or apoptotic changes and no cytostructural alterations were observed for 2, 4, 10, and 20 j,g doses (Okada etal. 

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