Application of Systematic Review Methods in an Overall Strategy for Evaluating Low-Dose Toxicity from Endocrine Active Chemicals

To safeguard public health, the US Environmental Protection Agency (EPA) must keep abreast of new scientific information and emerging technologies so that it can apply them to regulatory decision-making. For decades the agency has dealt with questions about what animal-testing data to use to make predictions about human health hazards, how to perform dose-response extrapolations, how to identify and protect susceptible subpopulations, and how to address uncertainties. As alternatives to traditional toxicity testing have emerged, the agency has been faced with additional questions about how to incorporate data from such tests into its chemical assessments and whether such tests can replace some traditional testing methods.

Endocrine active chemicals (EACs) have raised concerns that traditional toxicity-testing protocols might be inadequate to identify all potential hazards to human health because they have the ability to modulate normal hormone function, and small alterations in hormone concentrations, particularly during sensitive life stages, can have lasting and significant effects. To address concerns about potential human health effects from EACs at low doses, this report develops a strategy to evaluate the evidence for such low-dose effects.

Contents

• The National Academies of SCIENCES • ENGINEERING • MEDICINE
• COMMITTEE ON ENDOCRINE-RELATED LOW-DOSE TOXICITY
• BOARD ON ENVIRONMENTAL STUDIES AND TOXICOLOGY
• Acknowledgments
• Abbreviations and Acronyms
• Summary
  • STRATEGY FOR EVALUATING LOW-DOSE EFFECTS
  • IMPLEMENTING THE STRATEGY: EXAMPLE REVIEWS
• 1. Introduction
  • ADVANCES IN TOXICITY TESTING
  • ENDOCRINE ACTIVE CHEMICALS
  • DEFINING LOW DOSE
  • LOW-DOSE EFFECTS
  • NONMONOTONIC DOSE-RESPONSE CURVES
  • SYSTEMATIC REVIEW
  • STATEMENT OF TASK
  • COMMITTEE'S APPROACH
  • ORGANIZATION OF THE CONSENSUS STUDY REPORT
  • REFERENCES
• 2. Strategy for Evaluating Low-Dose Effects
  • OVERVIEW OF THE COMMITTEE'S STRATEGY
  • SURVEILLANCE
  • INVESTIGATION AND ANALYSIS
  • ACTIONS
  • FINDINGS AND RECOMMENDATIONS
  • REFERENCES
• 3. Phthalates and Male Reproductive-Tract Development
  • SYSTEMATIC REVIEW METHODS
  • RESULTS
  • EVIDENCE INTEGRATION FOR AGD
  • EVIDENCE INTEGRATION FOR FETAL TESTOSTERONE
  • EVIDENCE INTEGRATION FOR HYPOSPADIAS
  • CONSIDERATION OF LOW-DOSE EFFECTS
  • OTHER PHTHALATES
  • RELEVANCE TO ANIMAL TOXICITY TESTING
  • FINDINGS AND RECOMMENDATIONS
  • REFERENCES
• 4. Effect of Polybrominated Diphenyl Ethers on Neurodevelopment
  • SYSTEMATIC REVIEW METHODS
  • RESULTS
  • MECHANISTIC EVIDENCE
  • EVIDENCE INTEGRATION
  • ANALYSIS OF LOW-DOSE EFFECTS
  • RELEVANCE TO ANIMAL TOXICITY TESTING
  • FINDINGS AND RECOMMENDATIONS
  • REFERENCES
• 5. Lessons Learned and Reflections on the Statement of Task
  • COMMITTEE STRATEGY
  • CHARACTERIZING ADVERSITY
  • REFLECTIONS AND LESSONS LEARNED FROM THE SYSTEMATIC REVIEWS
  • LESSONS LEARNED FROM EVIDENCE INTEGRATION
  • OTHER ISSUES
  • REFERENCES
• APPENDIXES
  • Appendix A. Biosketches of the Committee on Endocrine-Related Low-Dose Toxicity
  • Appendix B. Workshop on Potential Case Studies for Unraveling Endocrine-Related Low-Dose Toxicity
  • Appendix C. Supporting Materials for the Phthalate (Animal) Systematic Review
  • Appendix D. Supporting Materials for the Phthalate (Human) Systematic Review
  • Appendix E. Supporting Materials for the PBDE (Animal) Systematic Review
  • Appendix F. Supporting Materials for the PBDE (Human) Systematic Review

Suggested citation:

National Academies of Sciences, Engineering, and Medicine. 2017. Application of Systematic Review Methods in an Overall Strategy for Evaluating Low-Dose Toxicity from Endocrine Active Chemicals. Washington, DC: The National Academies Press. doi: https://doi.org/10.17226/24758.