Cefic-lri Programme | European Chemical Industry Council

B18.2 – Incorporation of repeated dose study information for non-DNA-reactive carcinogens into the CPDB database and analysis of threshold values

Principal Investigator

Dr Sylvia Escher
Fraunhofer Institute for Toxicology and Experimental Medicine (ITEM)
Chemical Risk Assessment
Nikolai-Fuchs Straβe 1
30625 Hannover
Tel. 0049-511-5350-330


Prof Dr Mark Cronin, Liverpool John Moores University, Liverpool, UK, m.t.cronin@ljmu.ac.uk

Dr Chihae Yang, Molecular Networks GmbH (MN), Erlangen, DE, chihae.yang@molecular-networks.com


This project is planned as extension of the project CEFIC LRI project B18, named “Database on Carcinogen Dose-response, including Information on DNA-reactivity, for TTC and beyond”, which is currently in its reporting phase.

In this previous project, we updated the content of the CPDB database by including more recent studies into it. Further we distinguished genotoxic and non-genotoxic carcinogens and calculated TD50/TD25/TD10 and BMDL10 values from the dose response of the tumour finding. All values can be found in the updated CPDB databases, which will be published in the near future.

For the non-genotoxic compounds, the calculated BMDL and TDX values do only consider the tumour finding, as the CPDB database does not report non-neoplastic or pre-neoplastic lesions and their corresponding NOAELs. This led to the situation that threshold-based health-based guidance values cannot be derived for the non-DNA-reactive substances in the database. This would though be necessary to close the gap in evidence supporting the approach of applying the non-cancer Cramer Class thresholds to substances without concern for DNA-reactivity.

This project will therefore address the following objectives:

  1. Update the toxicological data of non-genotoxic compounds in the CPDB database: Add appropriate data from oral repeated dose study information for all compounds being judged as non-genotoxic in the CEFIC LRI B18 project
  2. Assign NOAEL values: Develop a transparent and systematic procedure to derive NOAEL values for all non-genotoxic compounds from the updated database
  3. Derive Threshold values: Assign Cramer classes to the compounds and derive 5th percentile thresholds. Compare to existing thresholds based on TD50/BMDLs and to TTC values from the Cosmos dataset/RepDose dataset
  4. Publish the updated CPDB database on a suitable website, ideally together with the CPDB database from the previous LRI B18 project. Prepare a peer-reviewed publication and show results at relevant scientific congresses

Timeline: September 2018 > August 2019

LRI funding: € 75 000

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