Cefic-lri Programme | European Chemical Industry Council

C6 – Toxicogenomic Approaches to Support Read-Across

Principal Investigator

Dr George Daston
Procter & Gamble
Victor Mills Society Research Fellow
Mason, OH
USA
daston.gp@pg.com
Tel. 513-622-3081

Collaborators

Russell Thomas, Director, National Center for Computational Toxicology (US EPA), russell.thomas@epa.gov
Maurice Whelan, Head, Systems Toxicology Unit (European Commission JRC), Ispra, IT, maurice.whelan@ec.europa.eu
Justin Lamb, President and CEO (Genometry), Cambridge, MA USA, justin@genometry.com
Karen Blackburn, Victor Mills Society Research Fellow (Procter & Gamble), Mason, OH USA, blackburn.kl@pg.com
Jorge Naciff, Principal Scientist (Procter & Gamble), Mason, OH USA, naciff.jm@pg.com
Shengde Wu, Principal Scientist (Procter & Gamble), Mason, OH USA, wu.s.3@pg.com
Nadira DeAbrew, Senior Scientist (Procter & Gamble), Mason, OH USA, deabrew.kn@pg.com
Sharon Stuard, Senior Scientist (Procter & Gamble), Mason, OH USA, stuard.sb@pg.com
Greg Carr, Research Fellow (Procter & Gamble), Mason, OH USA, carr.gj@pg.com

Description

The proposed project will combine existing work processes in chemical read-across with toxicogenomics data to define functional approaches that support read-across.  Specifically, we will:

– develop case studies for three chemical classes, one that affects development, one that affects male fertility, and one affecting liver function, showing the ability of gene expression data to identify comparable biological activity between class members, as well as to identify the limits in similarity beyond which biological activity is not equivalent;

  • develop pragmatic guidance for the use of connectivity mapping to demonstrate biological equivalency for structurally related compounds, to include
  • determine the minimal number of cell types, sampling times and concentrations needed to provide reliable toxicogenomics data to support read-across;
  • determine the extent of gene expression overlap needed to ensure toxicologic equivalency;
  • recommended approaches and software tools for querying and filtering large connectivity map databases to identify agents with similar biological activity
  • check the validity of the toxicogenomic data for a subset of the case study chemicals using an alternative high-throughput data source such as ToxCast.

We will also convene a small working meeting, with European regulators (and/or European scientists familiar with read-across under REACH), to critique our case studies.

Timeline: July 2018 > July 2021

LRI funding: € 382 664

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