Center Overview

The Center is developing new methods and tools, and continues to collaborate closely with EPA, Tox21 and other environmental scientists. New in vitro population-based assays and computer-based models that fill critical gaps in risk assessment are being developed and delivered. The emphasis is on their usability by the risk assessment community and the investigative toxicologists alike. The synthesis of data from a variety of sources will move the field of computational toxicology from a hypothesis-driven toward predictive science. The Center’s research in support of Tox21 and NexGen is contributing to the following Specific Objectives:

Objective 1: Develop a quantitative high-throughput screening (qHTS) approach to probe differential chemical effects in a population-based in vitro system.

    We conduct qHTS experiments using a panel of 1000+ genetically diverse/defined human lymphoblast cell lines representative of 9 human populations. We collect concentration-response cytotoxicity data on hundreds of chemicals relevant to human health assessment priorities.

Objective 2: Provide the computational toxicology solutions for risk characterization in NexGen assessments with a focus on point-of-departure and population variability.

    We use qHTS data from Objective 1 and publicly available genotyping and gene expression data to define pathways that may be responsible for differential sensitivity of human cell lines with an emphasis on the endocrine-disruption and other chemical-perturbed pathways. Also, we utilize our expertise in toxicology, risk assessment, statistics and modeling and develop prototype examples of chemical prioritization and evaluation in the tiered NexGen assessments.

Objective 3: Develop cheminformatics-based, as well as enhanced chemical-biological, models of in vivo reproductive and developmental toxicity that rely on concomitant exploration of chemical descriptors and population-based screening data.

    In this work, using historical data, we build rigorous QSAR as well as chemical-biological models for compounds known to bind or activate several major steroid and hormone receptors implicated in reproductive/developmental toxicity. In addition, using data from Objective 1, we develop models of reproductive/developmental toxicity by taking into account population diversity and, pathway information from Objective 2.

Organizational Structure of the Center Organizational Chart

Scientific Steering Committee:

External Advisory Board:

    George Daston, Ph.D., Proctor&Gamble.
    Alison Motsinger-Reif, Ph.D., is Associate Professor of Statistics at North Carolina State University.
    Raymond Tice, Ph.D., Head, Biomolecular Screening Branch, DNTP/NIEHS.
    Weida Tong, Ph.D., Director, Center for Bioinformatics, NCTR/FDA.
    Maurice Whelan, Ph.D., Head, Systems Toxicology Unit, Institute for Health and Consumer Protection, EU Joint Research Centre