Historically, regulations governing chemical use have often focused on widely used chemicals and acute human health effects of exposure to them, as well as their potential to cause cancer and other adverse health effects. As scientific knowledge has expanded there has been an increased awareness of the mechanisms through which chemicals may exert harmful effects on human health, as well as their effects on other species and ecosystems. Identification of high-priority chemicals and other chemicals of concern has prompted a growing number of state and local governments, as well as major companies, to take steps beyond existing hazardous chemical federal legislation. Interest in approaches and policies that ensure that any new substances substituted for chemicals of concern are assessed as carefully and thoroughly as possible has also burgeoned. The overarching goal of these approaches is to avoid regrettable substitutions, which occur when a toxic chemical is replaced by another chemical that later proved unsuitable because of persistence, bioaccumulation, toxicity, or other concerns.

Chemical alternative assessments are tools designed to facilitate consideration of these factors to assist stakeholders in identifying chemicals that may have the greatest likelihood of harm to human and ecological health, and to provide guidance on how the industry may develop and adopt safer alternatives. A Framework to Guide Selection of Chemical Alternatives develops and demonstrates a decision framework for evaluating potentially safer substitute chemicals as primarily determined by human health and ecological risks. This new framework is informed by previous efforts by regulatory agencies, academic institutions, and others to develop alternative assessment frameworks that could be operationalized. In addition to hazard assessments, the framework incorporates steps for life-cycle thinking—which considers possible impacts of a chemical at all stages including production, use, and disposal—as well as steps for performance and economic assessments. The report also highlights how modern information sources such as computational modeling can supplement traditional toxicology data in the assessment process.

This new framework allows the evaluation of the full range of benefits and shortcomings of substitutes, and examination of tradeoffs between these risks and factors such as product functionality, product efficacy, process safety, and resource use. Through case studies, this report demonstrates how different users in contrasting decision contexts with diverse priorities can apply the framework. This report will be an essential resource to the chemical industry, environmentalists, ecologists, and state and local governments.

Contents

• THE NATIONAL ACADEMIES
• COMMITTEE ON THE DESIGN AND EVALUATION OF SAFER CHEMICAL SUBSTITUTIONS: A FRAMEWORK TO INFORM GOVERNMENT AND INDUSTRY DECISIONS
• BOARD ON CHEMICAL SCIENCES AND TECHNOLOGY
• BOARD ON ENVIRONMENTAL STUDIES AND TOXICOLOGY
• Acknowledgments
• Summary
  • STATE OF THE ART OF EXISTING FRAMEWORKS FOR ALTERNATIVE ANALYSIS
  • THE COMMITTEE'S ALTERNATIVES ASSESSMENT FRAMEWORK
  • SCIENTIFIC INFORMATION AND TOOLS REQUIRED TO SUPPORT THE COMMITTEE'S FRAMEWORK
• 1. Introduction
  • RECENT DRIVERS RESULTING IN CHEMICAL ALTERNATIVES ASSESSMENT
  • GOVERNMENTAL EFFORTS TO DRIVE ADOPTION OF SAFER CHEMICALS
  • GROWTH IN EVALUATIVE APPROACHES
  • THE COMMITTEE'S TASK
• 2. Existing Frameworks and Approaches
  • SPECIFIC FRAMEWORKS CONSIDERED BY THE COMMITTEE
  • SPECIFIC TOOLS CONSIDERED BY THE COMMITTEE
  • OVERVIEW OF CHARACTERISTICS FOUND IN EXISTING FRAMEWORKS FOR CHEMICAL ALTERNATIVES ASSESSMENTS
• 3. The Committee's Framework
  • STEP 1: IDENTIFY CHEMICAL OF CONCERN
  • STEP 2: SCOPING AND PROBLEM FORMULATION
  • STEP 3: IDENTIFY POTENTIAL ALTERNATIVES
  • STEP 4: DETERMINE IF ALTERNATIVES ARE AVAILABLE; REFER CASES WITH LIMITED OR NO ALTERNATIVES TO RESEARCH AND DEVELOPMENT
  • STEP 5: ASSESS PHYSICOCHEMICAL PROPERTIES
  • STEP 6: ASSESS HUMAN HEALTH, ECOTOXICITY, AND COMPARATIVE EXPOSURE
  • STEP 7: INTEGRATION OF INFORMATION TO IDENTIFY SAFER ALTERNATIVES
  • STEP 8: LIFE CYCLE THINKING
  • STEP 9: OPTIONAL ASSESSMENTS
  • STEP 10: IDENTIFY ACCEPTABLE ALTERNATIVES AND REFER CASES WITH NO ALTERNATIVES TO RESEARCH AND DEVELOPMENT
  • STEP 11: COMPARE OR RANK ALTERNATIVES
  • STEP 12: IMPLEMENT ALTERNATIVES
  • STEP 13: RESEARCH / DE NOVO DESIGN
• 4. Scoping, Problem Formulation, and Identifying Alternatives
  • SCOPING, PROBLEM FORMULATION, AND IDENTIFYING ALTERNATIVES IN OTHER FRAMEWORKS
  • SCOPING IN THE COMMITTEE'S FRAMEWORK
  • PROBLEM FORMULATION IN THE COMMITTEE'S FRAMEWORK
  • IDENTIFYING ALTERNATIVES IN THE COMMITTEE'S FRAMEWORK
• 5. Physicochemical Properties and Environmental Fate
  • PHYSICOCHEMICAL PROPERTIES OF INTEREST
  • MEASURED PHYSICOCHEMICAL PROPERTY VALUES
  • METHODS FOR ESTIMATING SELECT PHYSICOCHEMICAL PROPERTIES
  • PHYSICOCHEMICAL PROPERTIES IN OTHER FRAMEWORKS
  • PHYSICOCHEMICAL PROPERTIES IN THE COMMITTEE'S FRAMEWORK
  • IMPLEMENTATION OF STEP 5 IN THE COMMITTEE'S FRAMEWORK
• 6. Comparative Exposure Assessment
  • EXPOSURE ASSESSMENT IN EXISTING FRAMEWORKS
  • THE COMMITTEE'S APPROACH TO EXPOSURE ASSESSMENT
  • Conduct Comparative Exposure Assessment (Step 6.3)
  • Integration of Exposure Assessment into Subsequent Steps
• 7. Assessment of Ecotoxicity
  • ECOTOXICOLOGY
  • ECOTOXICITY ASSESSMENT IN OTHER FRAMEWORKS
  • COMMITTEE'S FRAMEWORK FOR ECOTOXICITY ASSESSMENT
  • METHODS FOR HAZARD DETERMINATION
• 8. Human Health
  • TYPES OF DATA FOR HUMAN HEALTH ASSESSMENT
  • HOW HUMAN HEALTH IS CONSIDERED IN EXISTING FRAMEWORKS
  • HUMAN HEALTH IN THE COMMITTEE'S FRAMEWORK
  • IN VITRO DATA AND IN SILICO MODELS FOR CHEMICAL ALTERNATIVES ASSESSMENTS
  • IN VITRO AND IN SILICO DATA INTEGRATION: AN OPPORTUNITY FOR NEW INSIGHTS
  • IMPLEMENTATION OF STEP 6.1: HUMAN HEALTH ASSESSMENT IN THE COMMITTEE'S FRAMEWORK
  • FUTURE RESEARCH NEEDS
  • CONCLUSIONS
• 9. Integration of Information to Identify Safer Alternatives
  • INFORMATION NEEDED TO IMPLEMENT STEP 7 IN THE COMMITTEE'S FRAMEWORK
  • STRATEGIES TO ADDRESS TRADEOFFS AND UNCERTAINTY
  • Uncertainty Strategies (Orange Quadrant)
  • CONCLUSIONS
• 10. Life Cycle, Performance, and Economic Considerations
  • LIFE CYCLE, SOCIAL, PERFORMANCE, AND ECONOMIC CONSIDERATIONS IN OTHER FRAMEWORKS
  • LIFE CYCLE CONSIDERATIONS IN THE COMMITTEE'S FRAMEWORK
  • STEP 9: OPTIONAL ASSESSMENTS
• 11. Identifying, Comparing, and Implementing Alternatives
  • IDENTIFYING ACCEPTABLE ALTERNATIVES WITHIN EXISTING FRAMEWORKS
  • STEP 10: IDENTIFYING ACCEPTABLE ALTERNATIVES IN THE COMMITTEE'S FRAMEWORK
  • STEP 11: COMPARING ALTERNATIVES IN THE COMMITTEE'S FRAMEWORK
  • STEP 12: IMPLEMENTING ALTERNATIVES
• 12. Case Studies
  • CASE STUDY 1: CHEMICAL SUBSTITUTION OF A RESTRICTED SUBSTANCE (decaBDE)
  • CASE STUDY 2: CHEMICAL SUBSTITUTION OF A HAZARDOUS BIOLOGICALLY ACTIVE COMPOUND (GLITAZONE)
  • CONCLUSION
• 13. Chemical Design: An Opportunity for Innovation
  • INNOVATION WITHIN THE COMMITTEE'S ALTERNATIVES ASSESSMENT FRAMEWORK
  • OPPORTUNITIES FOR INNOVATION
  • SUMMARY
• References
• APPENDIXES
  • Appendix A Biographic Information of Committee Members
  • Appendix B Ecotoxicity in Frameworks
  • Appendix C Toxicological Priority Index (ToxPi)
  • Appendix D Overview of the GHS Classification Scheme in Hazard Classification

This project was supported by Contract EP-C-09-003, TO# 25 between the National Academy of Sciences and the U.S. Environmental Protection Agency Any opinions, findings, and conclusions, or recommendations expressed in this material are those of the author(s) and do not necessarily reflect the views of the sponsoring agencies or any of their subagencies.

NOTICE: The project that is the subject of this report was approved by the Governing Board of the National Research Council, whose members are drawn from the councils of the National Academy of Sciences, the National Academy of Engineering, and the Institute of Medicine. The members of the committee responsible for the report were chosen for their special competences and with regard for appropriate balance.