National Toxicology Program U.S. Department of Health and Human Services Annual Report for Fiscal Year 2 019 2019 Annual Report – National Toxicology Program Letter from the NIEHS and NTP Director In fiscal year (FY) 2019, NTP continued to advance toxicology and inform public health policy by providing information to decision makers and the public about substances in our environment. NTP scientists published more than 249 peer-reviewed research studies and reports on substances of public health concern, including per- and polyfluoroalkyl substances (PFAS), the organophosphorus nerve agent sarin, and others. Other notable research achievements in FY 2019 included a pioneering systematic review of whether exposure to traffic-related air pollution (TRAP) during pregnancy is associated with hypertensive disorders of pregnancy. NTP also published final monographs on antimony trioxide and Helicobacter pylori, both of which are now proposed for listing in the 15th Report on Carcinogens. Noteworthy events included a workshop to review alternative methods for human and veterinary rabies vaccine potency testing, a workshop which converged on cancer topics, and a webinar for alternative inhalation toxicity testing methods that emphasized in vitro and in silico methodologies. Rick Woychik, Ph.D., Acting Director, NIEHS and NTP. I invite you to read this report to learn about our work and what we (Photo courtesy of Steve McCaw.) accomplished in FY 2019 toward advancing toxicology and safeguarding public health by generating and communicating trusted scientific information. On October 3, 2019, Linda Birnbaum, Ph.D., DABT, ATS retired after 40 years as a federal scientist including 10 years (2009-2019) as Director of the NIEHS and NTP. We recognize and applaud Linda’s many accomplishments and her global leadership in toxicology and environmental health research. I am privileged to serve as Acting Director of both NIEHS and NTP and work with NTP Associate Director Brian R. Berridge, D.V.M., Ph.D., DACVP and our NTP agency partners at the National Institute for Occupational Safety and Health and the Food and Drug Administration. Together we will continue NTP’s critical role in the generation, interpretation, and communication of toxicological information that strengthens the science base and informs decisions that protect the health of Americans. Rick Woychik, Ph.D. Acting Director, NIEHS and NTP 2019 Annual Report – National Toxicology Program Table of Contents 1. FY 2019 at a Glance ....................................................................................................................... 1 1.1. Timeline ................................................................................................................................... 1 1.2. Completed NTP Reports and Publications .............................................................................. 2 1.3. NTP Public Health Impact........................................................................................................ 2 1.4. Highlights from 40 Years of Work ............................................................................................ 6 1.5. Dr. Linda Birnbaum Announces Retirement ............................................................................ 8 1.6. PFAS in the Spotlight .............................................................................................................. 9 1.7. New Interagency Memorandum of Understanding Aims to Improve Cardiovascular Safety of Pharmaceuticals ..................................................................................................................... 9 1.8. NTP Converges on Cancer .................................................................................................... 10 1.9. NTP Improving Tests of Developmental Neurotoxicity .......................................................... 11 1.10. Peer Review of Draft NTP Monograph on Organophosphorus Nerve Agent Sarin ................ 11 1.11. Additional Activities ................................................................................................................ 12 2. About NTP .................................................................................................................................... 13 2.1. Organizational Structure and Oversight ................................................................................. 13 2.2. Interagency Agreements ....................................................................................................... 14 2.3. Funding ................................................................................................................................. 16 2.4. Program Contact Information ................................................................................................. 18 3. Scientific and Public Input Opportunities ................................................................................. 19 3.1. NTP Board of Scientific Counselors ....................................................................................... 19 3.2. Scientific Advisory Committee on Alternative Toxicological Methods .................................... 21 3.3. Scientific Panels .................................................................................................................... 23 3.3.1. NTP Developmental and Reproductive Toxicity Reports Peer Reviewed in FY 2019 ............... 23 3.3.2. NTP Monographs Peer Reviewed in FY 2019 ........................................................................... 24 3.3.3. NTP Report on Carcinogens Monographs Peer Reviewed in FY 2019 ..................................... 24 3.4. Training Opportunities ........................................................................................................... 25 4. Research and Testing ................................................................................................................. 27 4.1. Tox21 .................................................................................................................................... 27 4.2. Testing and Toxicology Studies ............................................................................................. 31 4.3. NICEATM .............................................................................................................................. 31 4.3.1. NICEATM Webinars and Workshops ......................................................................................... 32 4.3.2. NICEATM Support of Tox21 ....................................................................................................... 33 4.3.3. Additional NICEATM Activities .................................................................................................... 33 4.4. ICCVAM................................................................................................................................. 38 4.4.1. Progress toward Strategic Roadmap Goals ............................................................................... 39 4.4.2. ICCVAM Meetings ...................................................................................................................... 40 4.4.3. ICCVAM Test Method Evaluation Activities ............................................................................... 40 4.4.4. ICCVAM International Validation Activities ................................................................................ 41 5. Literature Analysis....................................................................................................................... 43 5.1. Noncancer Research ............................................................................................................. 43 2019 Annual Report – National Toxicology Program 5.2. Report on Carcinogens .......................................................................................................... 47 5.2.1. Evaluating Cancer Hazards ....................................................................................................... 48 6. Partner Agency Research ........................................................................................................... 50 6.1. NTP at NIEHS........................................................................................................................ 50 6.1.1. Biomolecular Screening ............................................................................................................. 50 6.1.2. NTP Laboratory .......................................................................................................................... 51 6.2. NTP at NCTR ........................................................................................................................ 55 6.2.1. NTP at NCTR: Interagency Agreement Projects ........................................................................ 64 6.3. NTP at NIOSH ....................................................................................................................... 66 6.3.1. NTP at NIOSH: Immunotoxicology Research ............................................................................ 72 6.3.2. NTP at NIOSH: Occupationally Relevant Exposures ................................................................. 72 Appendix I: NTP Publications in FY 2019 ....................................................................................... 76 Appendix II: Testing and Toxicology Studies in FY 2019 .............................................................. 76 2019