https://ntp.niehs.nih.gov/go/milestones

History & Milestones

In the United States in the mid-to-late 1970s, there was growing concern about the potential for various substances in our environment to directly or indirectly cause illness and disease. In most cases, there simply wasn't enough scientific data to prove a link; systematic testing was needed to understand the effects of environmental substances on human health.

In response to this demand, NTP was established in 1978 by Joseph A. Califano, Jr., then Secretary of the U.S. Department of Health, Education and Welfare (today known as the U.S. Department of Health and Human Services). In October of 1981, Secretary of Health and Human Services Richard S. Schweiker granted permanent status to NTP as a government program.

NTP was established to:

  • Test chemicals of public health concern
  • Develop and validate new and better integrated test methods
  • Provide needed information to regulatory and research agencies
  • Strengthen the science base in toxicology

David P. Rall, who at the time was Director of the National Institute of Environmental Health Sciences of the National Institutes of Health, was named the first director of NTP.

Milestones

  • 1978

    • Department of Health, Education and Welfare establishes NTP.
    • David P. Rall, M.D., Ph.D., named first Director.
    • NTP publishes 100th technical report.

  • 1980

    • First Report on Carcinogens published; 26 listings.
    • NTP publishes 200th technical report.
    • Developmental toxicity testing initiated.

  • 1981

    • Department of Health and Human Services (HHS) transfers National Cancer Institute (NCI) Carcinogenesis Testing Program to NIEHS/NTP.

  • 1982

    • Immunotoxicology incorporated into testing strategy. Comprehensive testing battery defined to evaluate immune system alterations.
    • Reproductive Assessment by Continuous Breeding studies initiated.

  • 1985

    • Technical Reports series on carcinogenesis bioassay broadened to include toxicology evaluations.
    • Cellular and genetic toxicity integrated into cancer bioassays.

  • 1986

    • Standards for quality assurance for pathology established.
    • Five categories set to define levels of evidence of carcinogenic activity.
    • First systematic evaluation of the predictability of various genetic toxicity screens for cancer published.
    • 300th technical report published.

  • 1990

    • NIEHS/NTP establishes an interagency agreement with Centers for Disease Control/National Institute for Occupational Safety and Health (CDC/NIOSH) for immunotoxicity of workplace xenobiotics.

  • 1991

    • Kenneth Olden, Ph.D., named Director of NIEHS/NTP.
    • Toxicity Report series initiated.

  • 1992

    • NIEHS/NTP establishes interagency agreement with Food and Drug Administration/National Center for Toxicology Research (FDA/NCTR) for conducting comprehensive toxicological evaluations of substances of concern to the FDA.

  • 1993

    • 400th technical report published.

  • 1995

    • Scientific consensus reached toward mechanistic-based approaches for understanding toxicity.
    • International workshop on validation and regulatory acceptance of alternative toxicological methods convened with ad hoc Interagency Coordinating Committee on the Validation of Alternative Methods (ICCVAM).

  • 1996

    • HHS approves revised listing criteria for the Report on Carcinogens, allowing consideration of all relevant information.
    • Formal process for removing a listing from the Report on Carcinogens established.
    • NIEHS/NTP initiates agreement with CDC/National Center for Environmental Health (NCEH) to provide funding for expanded biomonitoring of environmental toxicants in the National Health and Nutrition Examination Survey.

  • 1997

    • Interagency Coordinating Committee on the Validation of Alternative Methods (ICCVAM) established to support the development, validation, acceptance, and harmonization of alternative toxicological test methods.
    • NIEHS/NTP establishes interagency agreement with CDC/NIOSH to characterize and evaluate adverse effects of complex occupational exposures.

  • 1998

    • NTP Interagency Center for the Evaluation of Alternative Toxicological Methods (NICEATM) established to convene scientific panels to evaluate alternative toxicological methods.
    • Center for the Evaluation of Risks to Human Reproduction (CERHR) established to conduct scientific assessments of the reproductive and developmental toxicity literature on selected environmental agents.
    • 8th Report on Carcinogens published; first report to apply revised listing criteria.

  • 1999

    • Regulatory acceptance of the Murine Local Lymph Node Assay and Corrositex® for dermal safety testing achieved through ICCVAM.

  • 2000

    • 9th Report on Carcinogens published; first report to apply new criteria to remove listings (saccharin and ethyl acrylate) and to upgrade listing based on consideration of mechanistic data (dioxin and ethylene oxide).
    • ICCVAM becomes permanent under NICEATM with passage of ICCVAM Authorization Act of 2000.
    • Center for Phototoxicology established.
    • Collaborations with the European Ramazzini Foundation of Oncology and Environmental Sciences formalized through NIEHS/NTP.
    • 500th technical report published.

  • 2002

    • 10th Report on Carcinogens published.
    • NICEATM initiates first international validation study with the European Centre for the Validation of Alternative Methods.

  • 2003

    • NTP-CERHR monograph series initiated.
    • Technical Report series for genetically modified models created.
    • Regulatory acceptance of revised Up-and-Down Procedures achieved through ICCVAM.
    • NICEATM and ICCVAM propose and define performance standards concept to allow for regulatory acceptance of proprietary test methods.

  • 2004

    • Use of toxic equivalency factor approach for cancer risk assessment of dioxin mixtures supported by NTP studies.
    • Roadmap completed and course planned for the 21st century to include greater use of high- and medium-throughput, mechanism-based assays.

  • 2005

    • 11th Report on Carcinogens published; first report to list biological agents.
    • NTP celebrates a quarter century of toxicology for public health and unveils a new toxicology for the 21st century.
    • Program to identify and evaluate high-throughput screening assays for toxicity testing initiated.
    • David A. Schwartz, M.D., Ph.D., named Director of NIEHS/NTP.

  • 2007

    • NIEHS/NTP funds dense single nucleotide polymorphisms mapping of 15 mouse strains to identify genetic variations as a tool for exploring genetic susceptibility to environmental disease.
    • Samuel H. Wilson, M.D., designated as Acting Director of NIEHS/NTP.
    • National Research Council (NRC) report Toxicity Testing in the 21st Century echoes themes from the NTP Roadmap (2004) in calling for new approaches to toxicity screening.
    • Prenatal exposure as default paradigm in toxicity testing adopted.

  • 2008

    • Collins et al. Perspectives article in Science responds to 2007 NRC report Toxicity Testing in the 21st Century by laying out a comprehensive federal agency response.
    • NIEHS/NTP establishes formal agreement with EPA and NIH Chemical Genomics Center for high-throughput toxicity testing.
    • NTP-CERHR monograph on bisphenol A released.
    • Linda S. Birnbaum, Ph.D., named Director of NIEHS/NTP.

  • 2009

    • New criteria for evaluating outcomes from studies on reproduction, development, or immune system announced.
    • NIEHS/NTP establishes International Cooperation on Alternative Test Methods (ICATM), a formal agreement to cooperate on alternative test methods with Europe, Japan, and Canada.

  • 2010

    • Chemical Effects in Biological Systems (CEBS)—a new database for housing, integrating, and managing data—published.
    • FDA joins Toxicology in the 21st Century (Tox21).

  • 2011

    • Scientific literature assessments expanded to include all non-cancer toxicities.
    • Korea joins ICATM.
    • Modified one generation reproduction study design adopted.
    • 12th Report on Carcinogens published.

  • 2012

    • Regulatory acceptance of BG1 luciferase estrogen receptor transactivation test method by EPA and first OEDC performance-based test guidelines for estrogen receptor agonists (PBTG 455) achieved through ICCVAM.

  • 2014

    • Nonneoplastic lesion atlas launched as guide for standardizing terminology in toxicologic pathology.
    • Systematic review methodology adopted for literature-based scientific assessments.
    • Research to evaluate West Virginia Elk River spilled chemicals combining high-throughput, computational, and traditional toxicology approaches initiated.
    • 13th Report on Carcinogens published.

  • 2015

    • Diversity outbred mouse demonstrated as a tool for identifying inter-individual variation in toxicity response.
    • Collaboration with EPA enables waivers of animal-based uterotrophic testing for EPA Endocrine Disruptor Screening Program, the first use of Tox21 approach by regulatory agency to replace animal testing.
    • Funding awarded to map gene expression during differentiation in mouse and human stem cells and to standardize zebrafish development protocols.

  • 2016

    • Analysis by NICEATM and EPA shows acute oral toxicity data can reliably assign EPA acute dermal hazard classifications, supporting new EPA policy to waive all acute lethality dermal studies for formulated pesticide products.
    • NTP Monograph on Immunotoxicity Associated with Exposure to PFOA and PFOS, first evaluation using a systematic review approach, published.
    • Research Report series created.
    • 14th Report on Carcinogens published.

  • 2017

    • National Institute of Standards and Technology (NIST) joins ICCVAM.
    • Integrated Chemical Environment (ICE) database that provides high-quality, curated data and analysis tools launched.
    • New method for analyzing genomic dose-response data announced.

  • 2018

    • ICCVAM's report A Strategic Roadmap for Establishing Approaches to Evaluate the Safety of Chemicals and Medical Products in the United States published.
    • New translational toxicology pipeline to increase NTP focus on predictive toxicology and enhance public health impact unveiled.
    • New EPA policy to accept in vitro methods instead of mouse tests for skin sensitization for pesticide ingredients and single chemicals under the Lautenberg Chemical Safety Act supported by NICEATM analysis.
    • Research Report on CLARITY-BPA core study published and grantees' data released.
    • Technical Reports on studies in rodents of radio frequency radiation used by cell phones published; the most expensive and technologically challenging studies ever undertaken by NTP.