Food for thought … on in silico methods in toxicology
Thomas Härtung · ALTEX · 2009
this series of articles has already addressed in vitro and in vivo tools (Hartung, 2007; Hartung, 2008b). With this contribution addressing computational toxicology we now try to complete considerations on the main methodological approaches in toxicology. However, we do still plan to address specific aspects, such as endpoints (omics, image technologies), high-throughput testing or physiology-based pharmaco-(toxico-)kinetic modelling (PBPK), in later issues. All of these aspects have major in silico components, which already shows how difficult it is to discuss in silico methods on their own. Indeed, their integration and interplay with in vivo and in vitro approaches is critical, at least in the way their development often depends critically on the input of either in vitro or in vivo data. this is a major difference to experimental approaches. An important consideration will thus be whether in silico methods are limited by the limitations of their input and whether we have any hope of overcoming their weaknesses or can only approximate them... there are some excellent introductions to and reviews of computational toxicology (Durham and Pearl, 2001; van de Waterbeemd, 2002; Greene, 2002; Veith, 2004, Helma, 2005; Simon-Hettich et al., 2006; Kavlock et al., 2008; Merlot, 2008; Nigsch et al., 2009; Greene and Naven, 2009). In addition, the ex-eCB website (http://ecb.jrc.ec.europa.eu/qsar/), hosted by Andrew Worth and his team (chronically understaffed given the high expectations) who act as key promoters of computational toxicology, is an excellent resource. the same holds true for the US-based International QSAR Foundation (http://www.qsari. org/) around Gil Veith, non-profit research organization devoted solely to creating alternative methods for identifying chemical hazards without further laboratory testing, and Angelo Vedanis Biographics laboratory 3R in Basel, Switzerland (see his article in this issue). As usual this article aims less at summarizing the state of the art than at feeding discussions and showing up the critical issues faced by a central element of this increasingly important approach to toxicology.