£700k awarded in the 2017 CRACK IT Challenge competition

In 2017 there were three Challenges:

DoCE (Dosing for Controlled Exposure) – ‘Dosing strategies for characterising in vitro dose-responses with increased relevance for in vivo extrapolation’

Chemical safety assessment is moving towards using suites of in vitro and in silico models to predict toxicity in response to chemical exposure, which could replace the need for animal studies. Quantitative extrapolation from in vitro to in vivo (QIVIVE) is reliant on accurate in vitro dose-response relationships based on actual concentrations in the test system. However, nominal concentrations are typically used and non-specific binding, evaporation and degradation of the test chemical can significantly alter the actual concentration in the system, leading to large errors.

Sponsored by Unilever and Shell, this Two Phase Challenge aims to establish improved methods and approaches to better account for bioavailability in vitro to enable robust QIVIVE.

Three teams have been awarded funding to carry out Phase 1 proof-of-concept studies*:

• Dr Tanja Hansen – Fraunhofer Institute for Toxicology and Experimental Medicine, Germany
• Dr Luise Henneberger – Helmholtz Centre for Environmental Research, Germany
• Professor Philipp Mayer - Technical University of Denmark

DARTpaths – ‘Mapping developmental and reproductive toxicity (DART) genes and pathways for cross-species comparison of toxic compound effects’

DART testing requires the use of large numbers of animals; for example, an OECD 414 prenatal development test requires ~800 rats and ~900 rabbits. There has been an increasing interest in using alternative cell-based, non-mammalian (e.g. zebrafish, nematode and Dictyostelium) and computational models, alongside adverse outcomes pathways, to improve the ability to predict chemicals with DART potential and reduce the reliance on animal models.

Sponsored by Shell and Syngenta, this Two Phase Challenge aims to develop a data model that maps orthologous DART genes and pathways between model organisms for cross-species comparison, integrating available information on the relationship between specific genes and physiology, or specific compounds and effects, to better predict potential DART effects.

Three teams have been awarded funding to carry out Phase 1 proof-of-concept studies*:

• Dr Paul Andrews – SimOmics Ltd, York
• Dr Barry Hardy – Douglas Connect GmbH, Switzerland
• Dr Raymond Pieters – University of Applied Sciences, Utrecht

RespiraTox – ‘In silico model for predicting human respiratory irritation’

Sponsored by Shell, this Single Phase Challenge aims to develop a quantitative structure-activity relationship (QSAR) tool that reliably predicts human respiratory irritation potential of chemicals.

The respiratory irritancy potential of chemicals is typically assessed and extrapolated from modified rodent acute inhalation toxicity studies. These studies use a large number of animals (up to 42 rodents for a single study) and have significant animal welfare concerns. Development of a QSAR tool that reliably predicts the respiratory irritancy potential of chemicals in humans will allow for the early identification of potential toxicities in candidate chemicals without having to use in vivo studies.

Successful Single Phase applicant for RespiraTox:

• Dr Sylvia Escher – Fraunhofer Institute for Toxicology and Experimental Medicine, Germany

*Phase 1 proof-of-concept stage winners for the Two Phase Challenges DoCE and DARTpaths have the opportunity to apply for Phase 2 where a single contract of up to £1 million will be awarded to one research team to deliver the full Challenge. The CRACK IT Two Phase Challenges competition is run using the Small Business Research Initiative (SBRI) process which is supported by Innovate UK.

Contractors for the Single Phase RespiraTox Challenge have one year and up to £100k to solve the Challenge.

Further information about CRACK IT Challenges competition process can be found on our website.