Cefic-lri Programme | European Chemical Industry Council

C6 – Toxicogenomic Approaches to Support Read-Across

Principal Investigator

Dr George Daston 

Victor Mills Society Research Fellow (Procter & Gamble)
Mason, OH USA
Daston.gp@pg.com
513-622-3081

Collaborators

Russell Thomas
Director, National Center for Computational Toxicology (US EPA)
Research Triangle Park, NC USA
Russell. thomas@epa.gov
1-919-541-5776

Maurice Whelan
Head, Systems Toxicology Unit (European Commission JRC)
Ispra, Italy
Maurice.whelan@ec.europa.eu

Justin Lamb
President and CEO (Genometry)
Cambridge, MA USA
justin@genometry.com
1-617-826-9849

Karen Blackburn
Victor Mills Society Research Fellow (Procter & Gamble)
Mason, OH USA
Blackburn.kl@pg.com
1-513-622-3040

Jorge Naciff
Principal Scientist (Procter & Gamble)
Mason, OH USA
Naciff.jm@pg.com
1-513-622-1167

Shengde Wu
Principal Scientist (Procter & Gamble)
Mason, OH USA
Wu.s.3@pg.com
1-513-622-2080

Nadira DeAbrew
Senior Scientist (Procter & Gamble)
Mason, OH USA
Deabrew.kn@pg.com
1-513-626-4067

Sharon Stuard
Senior Scientist (Procter & Gamble)
Mason, OH USA
Stuard.sb@pg.com
1-513-627-5838

Greg Carr
Research Fellow (Procter & Gamble)
Mason, OH USA
Carr.gj@pg.com
1-513-622-5401

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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