Evaluating Chemical and Other Agent Exposures for Reproductive and Developmental Toxicity

Evaluating Chemical and Other Agent Exposures for Reproductive and Developmental Toxicity

  • Publisher: National Academies Press
  • ISBN: 9780309073165
  • eISBN Pdf: 9780309567619
  • eISBN Epub: 9780309171397
  • Place of publication:  United States
  • Year of digital publication: 2001
  • Month: March
  • Pages: 262
  • Language: English

The United States Navy has been concerned for some time with protecting its military and civilian personnel from reproductive and developmental hazards in the workplace. As part of its efforts to reduce or eliminate exposure of Naval personnel and their families to reproductive and developmental toxicants, the Navy requested that the National Research Council (NRC) recommend an approach that can be used to evaluate chemicals and physical agents for their potential to cause reproductive and developmental toxicity. The NRC assigned this project to the Committee on Toxicology, which convened the Subcommittee on Reproductive and Developmental Toxicology, to prepare this report. In this report, the subcommittee recommends an approach for evaluating agents for potential reproductive and developmental toxicity and demonstrates how that approach can be used by the Navy.

This report has been reviewed in draft form by individuals chosen for their diverse perspectives and technical expertise, in accordance with procedures approved by the NRC's Report Review Committee. The purpose of this independent review is to provide candid and critical comments that will assist the institution in making its published report as sound as possible and to ensure that the report meets institutional standards for objectivity, evidence, and responsiveness to the study charge. The review comments and draft manuscript remain confidential to protect the integrity of the deliberative process. We wish to thank the following individuals for their review of this report: James Chen (National Center for Toxicological Research), George Daston (Procter and Gamble Company), Jerry Heindel (National Institute of Environmental Health Sciences), Grace Lemasters (University of Cincinnati), and John Young (National Center for Toxicological Research).

  • EVALUATING CHEMICAL AND OTHER AGENT EXPOSURES FOR REPRODUCTIVE AND DEVELOPMENTAL TOXICITY
  • Copyright
  • Preface
  • Contents
  • Abbreviations
  • EVALUATING CHEMICAL AND OTHER AGENT EXPOSURES FOR REPRODUCTIVE AND DEVELOPMENTAL TOXICITY
  • Summary
    • CONCLUSIONS AND RECOMMENDATIONS
      • Evaluative Process
        • Assessing the Available Data
        • Integration of Toxicity and Exposure Information
      • Insufficient Data Sets
      • Application of the Evaluative Process
      • Sources of Information
      • Research Recommendations
  • 1 Introduction
    • SUBCOMMITTEE'S TASK
    • ORGANIZATION OF THE REPORT
  • 2 The Evaluative Process: Part I. Assessing the Available Data
    • PRINCIPLES AND OBJECTIVES
      • Use of Data and Judgment
      • Weight of Evidence
      • Threshold Assumption
      • Narrative Statement
      • Certainty
      • Use All Relevant, Acceptable Data
      • Qualities and Limitations of Reproductive and Developmental Toxicity Studies
      • Characterizing Data
      • Expert Review Team
    • GENERAL DESCRIPTION
    • DETAILS OF THE EVALUATIVE PROCESS
      • Exposure Data
      • General Toxicological and Biological Parameters
        • Chemistry
        • Basic Toxicity
          • Acute Studies
          • Repeated-Dose Studies
          • Genetic Toxicity
        • Pharmacokinetics
      • Reproductive and Developmental Toxicity
        • Human Data
          • Weighing the Evidence
          • Case Reports and Clinical Series
          • Assessing Causality in Human Studies
        • Experimental Animal Toxicity
          • Utility and Limitations
          • Adverse Effect
  • 3 The Evaluative Process: Part II. Integration of Toxicity and Exposure Information
    • INTERPRETATION OF TOXICITY DATA
      • Default Assumptions To Be Considered in Assessing Reproductive and Developmental Toxicity Risk
        • Absorption
        • Cross-Species Extrapolation
        • Exposure Duration
        • Windows of Vulnerability
        • Additivity
    • QUANTITATIVE EVALUATION
      • Identification of the NOAEL and LOAEL
      • Calculation of the Benchmark Dose
      • Duration Adjustment
      • Uncertainty Factors
      • Calculation of the Unlikely Effect Level
      • Calculation of the Margin of Exposure (MOE)
      • Assessing a Degree of Concern
      • Application of Reproductive and Developmental Toxicity Data to Various Exposure Scenarios
      • Critical Data Needs
    • SUMMARY
  • 4 Incomplete or Insufficient Data Sets
    • PRINCIPLES TO MINIMIZE RISK
    • PRACTICAL APPLICATION
    • REDUCING UNCERTAINTY
  • 5 Recommendations
    • GENERAL RECOMMENDATIONS
    • RESEARCH RECOMMENDATIONS
  • References
  • Appendixes
    • Appendix A Application of the Recommended Evaluative Process to Specific Chemicals
      • JP-8 JET FUEL
        • Exposure Data
        • General Toxicological and Biological Parameters
          • Lethality
          • Acute Studies
            • Human Studies
            • Experimental Animal Studies
          • Repeated-Dose Studies
            • Human Studies
            • Experimental Animal Studies
          • Cancer
          • Genetic Toxicity
          • Disposition and Pharmacokinetics
        • Reproductive and Developmental Toxicity Data
          • Human Studies
          • Experimental Animal Studies
            • Developmental Toxicity
            • Reproductive Toxicity
        • Integration of Toxicity and Exposure Information
          • Interpretation of Toxicity Data
          • Quantitative Evaluation
          • Critical Data Needs
        • Summary
          • Human Exposure
          • Toxicology
            • Developmental Toxicity
            • Reproductive Toxicity
          • Quantitative Evaluation
            • Developmental Toxicity
            • Reproductive Toxicity
          • Certainty of Judgment and Data Needs
        • 1,1,1,2-TETRAFLUOROETHANE1
        • Exposure Data
        • General Toxicological and Biological Parameters
          • Acute Studies
          • Repeated-Dose Studies
          • Genetic Toxicity Studies
          • Carcinogenicity Studies
          • Other Toxicity
          • Pharmacokinetics
        • Reproductive and Developmental Toxicity Data
          • Human Studies
          • Experimental Animal Studies
            • Reproductive Toxicity
            • Developmental Toxicity Studies
        • Integration of Toxicity and Exposure Information
          • Interpretation of Toxicity Data
            • General Toxicity and Pharmacokinetics
            • Reproductive and Developmental Toxicity
            • Default Assumptions
          • Quantitative Evaluation
          • Critical Data Needs
        • Summary
          • Human Exposure
          • Toxicology
            • Developmental Toxicity
            • Reproductive Toxicity
          • Quantitative Evaluation
            • Reproductive and Developmental Toxicity
          • Certainty of Judgment and Data Needs
    • Appendix B Ascertaining Information on the Reproductive and Developmental Toxicity of Agent Exposures
      • SOURCES OF INFORMATION SPECIFIC TO REPRODUCTIVE AND DEVELOPMENTAL TOXICITY
        • Detailed Evaluations
          • California Environmental Protection Agency Hazard Identification Documents on Reproductive and Devel...
            • Description
            • Reproductive and Developmental Toxicity
            • Quality Control
            • Usefulness in Identifying Exposures that Pose a Substantial Risk of Reproductive or Developmental To...
          • Evaluative Process (Moore et al. 1995a,b; 1997)
            • Description
            • Reproductive and Developmental Toxicity
            • Quality Control
            • Usefulness in Identifying Exposures That Pose a Substantial Risk of Reproductive and Developmental T ...
          • National Institute of Environmental Health Sciences Center for the Evaluation of Risks to Human Repr...
            • Description
            • Reproductive and Developmental Toxicity
            • Quality Control
            • Usefulness in Identifying Exposures That Pose a Substantial Risk of Reproductive or Developmental To...
        • Informational Summaries
          • Reproductive Hazards of Industrial Chemicals: An Evaluation of Animal and Human Data
            • Description
            • Reproductive and Developmental Toxicity
            • Quality Control
            • Usefulness in Identifying Exposures That Pose a Substantial Risk of Reproductive or Developmental To...
          • REPROTEXT
            • Description
            • Reproductive and Developmental Toxicity
            • Quality Control
            • Usefulness in Identifying Exposures That Pose a Substantial Risk of Reproductive or Developmental To...
          • REPROTOX
            • Description
            • Reproductive and Developmental Toxicity
            • Quality Control
            • Usefulness in Identifying Exposures That Pose a Substantial Risk of Reproductive or Developmental To...
          • Chemically Induced Birth Defects
            • Description
            • Reproductive and Developmental Toxicity
            • Quality Control
            • Usefulness in Identifying Exposures That Pose a Substantial Risk of Reproductive or Developmental To...
          • Shepard's Catalog of Teratogenic Agents
            • Description
            • Reproductive and Developmental Toxicity
            • Quality Control
            • Usefulness in Identifying Exposures That Pose a Substantial Risk of Reproductive or Developmental To...
          • TERIS
            • Description
            • Reproductive and Developmental Toxicity
            • Quality Control
            • Usefulness in Identifying Exposures That Pose a Substantial Risk of Reproductive or Developmental To...
        • Bibliographic Resources
          • Developmental and Reproductive Toxicology Data Base
            • Description
            • Reproductive and Developmental Toxicity
            • Quality Control
            • Usefulness in Identifying Exposures That Pose a Substantial Risk of Reproductive or Developmental To...
          • Environmental Teratology Information Center Backfile
            • Description
            • Reproductive and Developmental Toxicity
            • Quality Control
            • Usefulness in Identifying Exposures That Pose a Substantial Risk of Reproductive and Developmental...
        • Primary Data
          • National Toxicology Program Teratology Studies
            • Description
            • Reproductive and Developmental Toxicity
            • Quality Control
            • Usefulness in Identifying Exposures That Pose a Substantial Risk of Reproductive and Developmental...
          • NTP Reproductive Assessment by Continuous Breeding Studies
            • Description
            • Reproductive and Developmental Toxicity
            • Quality Control
            • Usefulness in Identifying Exposures That Pose a Substantial Risk of Reproductive and Developmental...
          • NTP Short-Term Developmental and Reproductive Toxicity Studies
            • Description
            • Reproductive and Developmental Toxicity
            • Quality Control
            • Usefulness in Identifying Exposures That Pose a Substantial Risk of Reproductive and Developmental...
      • ADDITIONAL SOURCES THAT MAY INCLUDE INFORMATION ON REPRODUCTIVE AND DEVELOPMENTAL TOXICITY
        • Detailed Evaluations
          • Agency for Toxic Substances and Disease Registry Toxicological Profiles
            • Description
            • Reproductive and Developmental Toxicity
            • Quality Control
            • Usefulness in Identifying Exposures That Pose a Substantial Risk of Reproductive or Developmental To...
          • National Institute for Occupational Safety and Health Criteria Documents
            • Description
            • Reproductive and Developmental Toxicity
            • Quality Control
            • Usefulness in Identifying Exposures That Pose a Substantial Risk of Reproductive or Developmental To...
          • International Agency for Research on Cancer Monographs on the Evaluation of Carcinogenic Risks to Humans
            • Description
            • Reproductive and Developmental Toxicity
            • Quality Control
            • Usefulness in Identifying Exposures That Pose a Substantial Risk of Reproductive or Developmental To...
          • International Programme on Chemical Safety Environmental Health Criteria Documents
            • Description
            • Reproductive and Developmental Toxicity
            • Quality Control
            • Usefulness in Identifying Exposures That Pose a Substantial Risk of Reproductive or Developmental To...
          • EPA Integrated Risk Information System
            • Description
            • Reproductive and Developmental Toxicity
            • Quality Control
            • Usefulness in Identifying Exposures That Pose a Substantial Risk of Reproductive or Developmental To...
          • EPA National Center for Environmental Assessment Documents
            • Description
            • Reproductive and Developmental Toxicity
            • Quality Control
            • Usefulness in Identifying Exposures that Pose a Substantial Risk of Reproductive and Developmental T...
        • Informational Summary
          • Chemical Hazards of the Workplace
            • Description
            • Reproductive and Developmental Toxicity
            • Quality Control
            • Usefulness in Identifying Exposures That Pose a Substantial Risk of Reproductive or Developmental To...
        • Bibliographic Resources
        • Primary Data
          • National Toxicology Program Toxicology Report Series
            • Description
            • Reproductive and Developmental Toxicity
            • Quality Control
            • Usefulness in Identifying Exposures That Pose a Substantial Risk of Reproductive or Developmental To...
          • Organization for Economic Cooperation and Development Screening Information Data Set Profiles
            • Description
            • Reproductive and Developmental Toxicity
            • Quality Control
            • Usefulness in Identifying Exposures That Pose a Substantial Risk of Reproductive or Developmental To...
    • Appendix C Human Study Designs
    • Appendix D Experimental Animal and In Vitro Study Designs
      • DEVELOPMENTAL TOXICITY
        • Types of Studies
          • Prenatal Developmental Toxicity
          • Developmental Neurotoxicity
          • In Vitro Assays
        • Interpretation
      • REPRODUCTIVE TOXICITY
        • Manifestations
          • Male Reproductive Toxicity
          • Female Reproductive Toxicity
        • Types of Studies
          • Single-Generation Reproduction Study
          • Multigeneration Reproduction Study
          • Reproductive Assessment by Continuous Breeding Study
          • Serial Mating Study (Dominant Lethal Study)
          • Total Reproductive Capacity
        • Interpretation
          • Male Indices
            • Organ Weight
            • Organ Morphology
            • Sexual Behavior
            • Sperm Evaluation
            • Endocrine Evaluations
            • Biochemical Markers of Reproductive Exposure and Effect
            • In Vitro Methods
          • Female Indices
            • Cytology Abnormalities
            • Weight and Morphology Changes
            • Biochemical Changes
            • Alterations in Age at Puberty or Reproductive Senescence
            • Endocrine Parameters
            • In Vitro and Perfusion Systems
            • Breast Milk

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