2018 Annual Report - National Toxicology Program

Welcome to the 2018 Annual Report"The NTP serves a critical role for our nation. It provides a unique, consolidated venue for toxicologyresearch, testing, and analysis to occur." – Dr. Linda Birnbaum, NIEHS and NTP DirectorRead the 2018 Letter from the NIEHS and NTP Director.FY 2018 at a GlanceLearn About Us Completed NTP Reports andPublications About NTP NTP Public Health Impact Brian Berridge Takes the Helmat the National ToxicologyProgramMoreScientific and Public InputOpportunities Organizational Structure andOversight NTP Board of ScientificCounselors Interagency Agreements SACATM Funding Scientific PanelsMoreMore

Research and TestingLiterature AnalysisPartner Agency Research Tox21 Noncancer Research NTP at NIEHS Testing and ToxicologyStudies Report on Carcinogens NTP at NCTR NICEATM NTP at NIOSH ICCVAMThe NTP Annual Report is produced by the NTP Office of Liaison, Policy, and Review. The text is not copyrighted and can bereprinted without permission. If you use parts of the Annual Report in a publication, please provide us a copy for our records. Wewelcome your comments and suggestions.Official Citation: National Toxicology Program. Annual Report for Fiscal Year 2018. Research Triangle Park, NC: NationalToxicology Program; 2019. Available from r of Office of Liaison, Policy, and Review and Editor -in-Chief: Mary Wolfe Managing Editor: Joshua Cleland (ICF)

2018 Annual Report – ContentsContentsContents .3Letter from the NIEHS and NTP Director.6FY 2018 at a Glance .7FY 2018 Timeline.9Completed NTP Reports and Publications .12Publications during FY 2018 . 12NTP Public Health Impact.13Use of NTP Study Data or Recommendations by Federal and State Health Regulatory and ResearchAgencies in FY 2018. 13Brian Berridge Takes the Helm at the National Toxicology Program .17Tox Challenge – Stage Two Winners Announced .18New Roadmap Guides Progress toward Replacing Animal Use .19NTP Releases Findings from Two CLARITY-BPA Study Components .20NTP Cell Phone Studies – Experts Recommend Elevated Conclusions .21Federal Partners Put Tox21 Plan into Action.22NTP Framework for Innovation Rolled Out at Board Meeting .23ICCVAM Publishes 2016–2017 Biennial Report .24PFAS in the Spotlight across the Globe.25Additional Activities.26Learn About Us .27About NTP .28Organizational Structure and Oversight.29Interagency Agreements.30FDA/NCTR. 30CDC/NIOSH. 30NIH/NCATS/DPI. 30DOE/ORNL . 31EPA/NCCT. 31EPA/NCEA. 31NIST . 31Funding.32NIEHS Contracts That Supported NTP Activities in FY 2018 . 32Program Contact Information.34Scientific and Public Input Opportunities.35NTP Board of Scientific Counselors.36NTP Board of Scientific Counselors Membership Roster FY 2018 . 373

2018 Annual Report – ContentsSACATM.38SACATM Membership Roster FY 2018. 39Scientific Panels .40NTP Technical Reports Peer Reviewed in FY 2018 . 40NTP Research Reports Peer Reviewed in FY 2018 . 40NTP Report on Carcinogens Monographs Peer-Reviewed in FY 2018 . 41Training Opportunities .42NIEHS/NTP Training Program Postdoctoral Fellows in FY 2018 . 42Research and Testing.43Tox21.44Testing and Toxicology Studies .52About Testing and Toxicology Studies . 53Disposition, Metabolism, and Toxicokinetic Studies . 54Genetic Toxicity Studies. 56Organ System Toxicity Studies . 61Modified One-Generation Reproduction Studies . 65Toxicology and Carcinogenicity Studies . 67Toxicogenomic Studies . 73NICEATM .77About NICEATM . 78NICEATM Webinars and Workshops . 79NICEATM Support of Tox21. 81Additional NICEATM Activities . 82ICCVAM.86About ICCVAM. 87A Strategic Roadmap for Establishing New Approaches to Evaluate the Safety of Chemicals and MedicalProducts in the United States. 88ICCVAM Meetings . 89ICCVAM Test Method Evaluation Activities . 90ICCVAM International Validation Activities . 92Literature Analysis .94Noncancer Research .95Ongoing Noncancer Health Effects Projects . 95Report on Carcinogens.99About the Report on Carcinogens . 100Report Activities . 101Report Substances Selected for Evaluation . 102Partner Agency Research.103NTP at NIEHS.1044

2018 Annual Report – ContentsBiomolecular Screening . 105NTP Laboratory. 107NTP at NCTR.110About NTP at NCTR. 111NTP at NCTR: Interagency Agreement Projects. 123NTP at NIOSH .126About NTP at NIOSH . 127NTP at NIOSH: Immunotoxicology Research . 135NTP at NIOSH: Occupationally Relevant Exposures. 137Appendix: Publications during FY 2018.140NTP Reports and Documents .140Research Reports . 140Toxicity Reports . 140Technical Reports . 140RoC Monograph. 141Journal Articles and Book Chapters.1415

2018 Annual Report – Letter from DirectorLetter from the NIEHS and NTP DirectorIn fiscal year (FY) 2018, NTP continued to advance toxicologyand inform public health policy by providing information todecision makers and the public about substances in ourenvironment. Numerous studies were published on substancesof public health concern, such as flame retardants, cell phoneradiofrequency radiation, and widely used industrial chemicals.Among these is the final report from the CLARITY-BPA corestudy and data sets from CLARITY-BPA grantee studies toevaluate the range of potential health effects from BPA in rats.In addition, NTP engaged in several activities to advancealternatives to animal testing. Particularly noteworthy waspublication of the Strategic Roadmap for Establishing NewApproaches to Evaluate the Safety of Chemicals and MedicalProducts in the United States, a consensus perspectivedeveloped with input from many groups. The “Tox21” consortiummet to discuss the new Toxicology in the 21st Century (Tox21)strategic plan that will continue to refine prediction of chemicaltoxicity to humans.NTP continued its systemic review literature activities to identifypotential hazards for human health. In partnership with the NIHCountermeasures Against Chemical Threats (CounterACT)Program, NTP conducted a systematic review to assess longterm neurological effects following acute exposure to theorganophosphorus nerve agent sarin. Antimony trioxide andHelicobacter pylori were evaluated for possible listing in thecongressionally mandated Report on Carcinogens.Dr. Birnbaum has served as the Director ofthe National Institute of EnvironmentalHealth Sciences (NIEHS) and the NationalToxicology Program (NTP) since 2009.(Photo courtesy of Steve McCaw.)I invite you to read this report to learn about our work and what weaccomplished in FY 2018 toward advancing toxicology andsafeguarding public health by generating and communicatingtrusted scientific information.Linda S. Birnbaum, Ph.D., D.A.B.T., A.T.S.6

2018 Annual Report – FY 2018 GlanceFY 2018 at a GlanceFY 2018 TimelineHighlighted NTP activities in FY 2018.Completed NTP Reports and PublicationsNTP studies are published in various NTP report series after undergoing peer review.NTP reports published in FY 2018 or expected for peer review in FY 2019 are listed.Full citations for NTP reports, journal publications, and book chapters published duringFY 2018 are provided as an appendix to this section.NTP Public Health ImpactFederal and state regulatory agencies use NTP study data and recommendations when considering theneed to test and regulate specific chemicals to protect human health.Brian Berridge takes the Helm at the NTPAs NTP’s new Associate Director, Brian Berridge, D.V.M., Ph.D., hopes to help NTPintegrate cutting-edge toxicology methods, including animal studies, cell-based toxicitytesting, and data intensive computer modeling.Tox Challenge – Stage Two Winners AnnouncedNTP names five winners of stage two of the Transform Toxicity Testing Challenge forproducing practical new rapid chemical testing technologies.Roadmap to Guide Progress Toward Replacing Animal UseThe newly published Strategic Roadmap for Establishing New Approaches to Evaluatethe Safety of Chemicals and Medical Products in the United States will guide progresstoward replacing use of animals for safety testing of drugs and chemicals in theUnited States.7

2018 Annual Report – FY 2018 GlanceNTP Releases Findings from Two CLARITY-BPA Study ComponentsThe newly released draft CLARITY-BPA report presents research from an initiative tostudying the full range of potential health effects in rats from exposure tobisphenol A (BPA).NTP Cell Phone Studies — Experts Recommend ElevatedConclusionsA panel of external scientific experts convened by NTP recommended that someconclusions be changed to indicate stronger evidence that cell phone radiofrequencyradiation (RFR) caused tumors in rats.Federal Partners Put Tox21 Plan into ActionThe new Toxicology in the 21st Century (Tox21) strategic plan promotes anautomated, high-throughput approach to rapidly measure the toxicity of chemicals.NTP Framework for InnovationSpeaking to the Board of Scientific Counselors, NTP Associate Director BrianBerridge, D.V.M., Ph.D., introduced the NTP Translational Toxicology Pipeline Plan forstrategic realignment.ICCVAM Publishes 2016–2017 Biennial ReportThe Interagency Coordinating Committee on the Validation of Alternative Methods(ICCVAM) Biennial Report summarizes activities of 16-member agencies that require,use, generate, or disseminate toxicological and safety testing information.PFAS in the Spotlight across the GlobeNIEHS and NTP Director Linda Birnbaum, Ph.D., testifies at the U.S. SenateSeptember 26 hearing titled “The Federal Role in the Toxic PFAS Chemical Crisis.”Additional ActivitiesAn overview of additional meetings with stakeholders and the scientific community inwhich NTP participated.8

2018 Annual Report – FY 2018 Glance – Timeline of EventsFY 2018 TimelinePeer Review of Draft NTP Approach to Genomic DoseResponse ModelingOctober 2017An expert panel was convened October 23–25 to review andprovide NTP scientific input on the elements of its proposedapproach.Alternative Test Methods to Reduce Vertebrate AnimalTesting Under TSCANovember 2017On November 2, EPA and NICEATM cosponsored a publicmeeting to obtain input toward development of an EPA strategicplan that promotes the development and implementation ofalternative test methods and strategies.NTP Board of Scientific Counselors MeetingDecember 2017At the December 7–8 meeting, th

Completed NTP Reports and Publications . NTP studies are published in various NTP report series after undergoing peer review. NTP reports published in FY 2018 or expected for peer review in FY 2019 are listed. Full citations for NTP reports, journal publications, and book chapters published during FY 2018 are provided as an appendix to this .