PAPER TITLE:
Towards a structure activity relationship (SAR) for nanoparticles

AUTHOR: Prof. Ken Donaldson, University of Edinburgh

ABSTRACT: There is clear and present need for short-term testing of hazard in order to gain information towards risk assessment of nanoparticles. However, the large number of nanoparticles and their variants, different sizes and coatings for instance, that require testing and ethical pressure towards non-animal testing means that expensive animal bioassay is precluded. The only rational way to achieve a situation where we do not need to test every single NP and its variants in toxicology tests is to relate the physicochemical characteristics of NP with their toxicity in a SAR (Structure Activity Relationship) model. If such a model were to be developed then, ideally, an untested particle could have its toxicity predicted on the basis of its physico-chemistry. There is sufficient knowledge from particle toxicology to allow rational choice of assays on which to base first attempts towards relating particle structure to toxic activities that are important for disease, especially ability to cause inflammation. In the University of Edinburgh we are carrying out two such studies, attempting to relate nanoparticle structure to biological activity :- 1) In a Colt Foundation-funded study using 13 metal oxide nanoparticles with free radical generation and oxidative stress as the structures and inflammation as the activity ; 2) In a NERC–funded pilot study using a panel of 20 nanoparticles with varying structures and simple measures of cellular toxicity and oxidative tress as the activities.
In addition we have just completed a study examining carbon nanotubes in the light of the asbestos structure/activity relationship. This study demonstrates that carbon nanotubes conforms to the asbestos structure /activity paradigm in terms of pathogenic behaviour in a short term model.