Food for thought … on alternative methods for nanoparticle safety testing

Abstract

Nano is a big thing in toxicology. Articles, journals, and conferences are mushrooming, paralleling the rise of nanotechnologies but also showing the hunger of toxicology for new objects to study. Perhaps it would be better to focus on new approaches first? Nanomedicine promises new solutions for old problems, but what about the old problems of toxicology? It is a fallacy to assume that one can gain beneficial effects in the human organism without unwanted collateral effects. First, any biologically active agent perturbs physiology, hopefully as a corrective for the patient but at least requiring compensatory reactions of the healthy. Second, few agents are specific enough to have only one effect, but it is rare that we want all the effects and in the given mix of strengths. third, many agents show excess toxicity – even desired effects often become negative if excessively stimulated. this increase in negative effects is directly linked to more sensitive subpopulations (children, elderly, the diseased, those with genetic polymorphisms, etc.). thus, the promise of nanoparticles (NP) may be paid for in possible side-effects, i.e., toxicities (Garnett et al., 2006). For most manufactured NP, toxicity data are unavailable, with some exceptions for carbon black, titanium dioxide, iron oxides, and amorphous silica (Di Giacchino et al., 2009). So far nanoparticles and other nanomaterials (I will use the abbreviation NP for both but primarily thinking of particles or fibers and not e.g. nano-thick films) are, for the most part, treated by regulatory toxicology as chemicals (see last issue of this series, Hartung, 2010b). The most common definitions for NP include materials with dimensions from 1 nm (size of a sugar molecule) to 100 nm (size of a virus). Regulatory frameworks are on the way, opening up possibilities for alternative approaches (Sauer, 2009). Whether the differences between NP and their parent compounds are actually small or big problems, remains to be seen. But to quote Albert einstein: “Anyone who doesn’t take truth seriously in small matters cannot be trusted in large ones either.” When discussing alternative methods for nanoparticle toxicology, we might first look at some phrase permutations – leaving out one word in each iteration: – Alternative methods for toxicology – Methods for nanoparticle toxicology – Alternative nanoparticle toxicology – Alternative nano-methods Consideration 1: Alternative or advanced methods for toxicology?