ABSTRACT
Einstein, “Anyone who doesn’t take truth seriously in small matters cannot be trusted in large ones either.” 5.2 Alternative or Advanced Methods in
ToxicologyThe term “alternative methods” is most commonly understood as “alternative to animal experiments” or at least using refinement and reduction alternatives to traditional animal experiments. Recently, the catch phrase “toxicology for the 21st century” (Tox-21c) generated an atmosphere of departure, more on the west side of the Atlantic, emphasizing the technological needs and opportunities for change. Fortunately, the two paths normally converge, and we can see them as two sides of the same coin-the most humane science is also the best science. There is a broad base of literature highlighting the ethical concerns, costs [17, 18], limited predictivity [19-21], and limited throughput [22, 23] of current approaches that, for the most part, were developed some decades ago for drug safety testing and subsequently were adapted to pesticides, chemicals, cosmetics, and foodstuffs. These limitations serve as the driving forces for change on both sides of the Atlantic [24]. While there is progress, particularly in some areas of topical and acute toxicity [25], progress for the more demanding systemic and chronic toxicities has been limited [26]. Is there any reason to assume that nanotoxicology would not benefit from alternative methods, for example, that they are less applicable to particles than to dissolved substances? Indeed, some theoretical considerations apply: the in vitro kinetics of particles might differ, that is, their behavior in cell culture. This might include particle clumping (aggregation), binding to plastic, or floating on the cell culture media surface, all of which would alter cellular exposure and, thus, the concentration-response curve. Similarly, exposure to air and nonphysiological culture conditions might affect the experiments. Also, specific artifacts have interfered with cytotoxicity measures (MTT) 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide as typically applied in alternative methods [27]. Later, we will discuss some general problems of alternative methods use for NPs. However, altogether nanotoxicology is likely a driving force and not a stumbling block toward the use of
modern approaches in toxicology [28]. These modern approaches offer the necessary level of standardization [29] that other experimental approaches often lack. The call for in vitro approaches is loud [6, 30, 31]. 5.2.1 Do We Need Special Methods for Nanotoxicology?
