IVIVE

Background

The safety assessment of new chemicals across the industrial chemical, agrochemical, pharmaceutical and consumer product sectors has long relied on high dose treatments in animals with default methods for extrapolating observed results to low level exposures in human populations. These traditional ‘whole-animal’ methods are expensive, can use many animals, and can sometimes be misleading with respect to human safety risk. As a result, increasing emphasis has centred on the development of predictive in vitro models for endpoints of toxicity, and their use to provide mode-of action understanding within the risk assessment process. Although progress has been made in developing in vitro models to predict some chemical toxicities such as skin irritation and corrosion, models to detect systemic toxicity across multiple organs are not currently available. Recently published opinions by the EU Scientific Committee on Consumer Safety (1) and a review by experts selected by the European Commission (2) indicate that, in the future, greater priority needs to be given to developing non-animal approaches which provide biological and chemical concentration-response data that can be integrated into consumer exposure and safety risk assessments. In 2007 the US National Research Council (NRC) issued its landmark report on “Toxicity Testing in the 21st Century: A Vision and a Strategy” (TT21C; (3)). The report sees a future in which routine toxicity testing would be conducted in human cells, human tissue surrogates, or human cell lines in vitro by evaluating cellular responses in a suite of toxicity pathway assays. These tools would enable risk assessors to predict regions of exposure that are expected to be without adverse consequences, rather than making predictions on the incidence of specific adverse responses in human populations. A key element to the realisation of this vision is the development of systems to understand exposure parameters in vitro and their extrapolation to inform safe in vivo exposure/in use scenarios. This will be the focus for this Challenge.

3Rs benefits

Historically, ‘alternative’ methods in toxicology have aimed to reproduce data generated using animal-based models. The aim of this Challenge is not to predict animal toxicity data but rather focus on safety risk assessment based on data relevant to human use as outlined in the TT21C vision. As such, if successful long term, the Challenge will ultimately provide tools and a means to address safety without use of animals.

Challenge winner

Project team led by:

• Dr Dominic Williams, University of Liverpool £997,634.

Full Challenge information