Standing Operating Procedures for Developing Acute Exposure Guideline Levels for Hazardous Chemicals -- Copyright -- Preface -- Contents -- Introduction -- REVIEW OF THE NAC DOCUMENT -- REFERENCES -- Roster National Advisory Committee for Acute Exposure Guideline Levels (NAC/AEGL Committee) for Hazardous Substances -- COMMITTEE MEMBERS -- Past Committee Members -- Participants from Cooperative Partner Countries -- Other Participants -- Oak Ridge National Laboratory Staff -- AEGL Program Senior Staff -- Appendix -- Preface -- 1. Overview of AEGL Program and NAC/AEGL Committee -- HISTORY -- PURPOSE AND OBJECTIVES OF THE AEGL PROGRAM AND THE NAC/AEGL COMMITTEE -- COMMITTEE MEMBERSHIP AND ORGANIZATIONAL STRUCTURE -- SELECTION OF CHEMICALS FOR AEGL DEVELOPMENT -- SCIENTIFIC CREDIBILITY OF AEGL VALUES -- THE AEGL DEVELOPMENT AND PEER-REVIEW PROCESS -- Stage 1: Draft AEGLs -- Stage 2: Proposed AEGLs -- Stage 3: Interim AEGLs -- Stage 4: Final AEGLs -- OPERATION OF THE NAC/AEGL COMMITTEE -- VALUE OF A COLLABORATIVE EFFORT IN THE AEGL PROGRAM -- APPLICATIONS OF THE AEGL VALUES -- 2. Derivation of AEGL Values -- 2.1 CHARACTERIZATION OF AEGLS -- 2.2 EMPIRICAL TOXICOLOGIC ENDPOINTS AND METHODS FOR DETERMINING EXPOSURE CONCENTRATIONS USED TO DERIVE AEGLS 1, 2, AND 3 -- 2.2.1 Selection of the Highest Exposure Level at Which the Effects That Define an AEGL Are Not Observed -- 2.2.2 Selection of Health-Effect Endpoints for AEGL-1, AEGL-2, and AEGL-3 -- 2.2.2.1 AEGL-1 Endpoints -- 2.2.2.1.1 No Value Established-AEGL-1 Is Close to or Exceeds AEGL-2 -- 2.2.2.1.2 No Value Established-Insufficient Data -- 2.2.2.1.3 Highest Experimental Exposure Without an AEGL-1 Effect -- 2.2.2.1.4 Effect Level for a Response -- 2.2.2.2 AEGL-2 Endpoints -- 2.2.2.2.1 Highest Experimental Exposure Without an AEGL-2 Effect.

2.2.2.2.2 Effect Level for a Toxic Response That Was Not Incapacitating or Not Irreversible -- 2.2.2.2.3 A Fraction of the AEGL-3 Value -- 2.2.2.3 AEGL-3 Endpoints -- 2.2.2.3.1 Highest Exposure Level That Does Not Cause Lethality-Experimentally Observed Threshold (AEGL-3 NOAEL) -- 2.2.2.3.2 Highest Exposure Level That Does Not Cause Lethality-Estimated Lethality Threshold-One-Third of the LC50 -- 2.2.2.3.3 Highest Exposure Level That Does Not Cause Lethality-Benchmark Exposure Calculation of the 5% and 1% Response -- 2.2.2.3.4 Effect Level for a Response -- 2.3 GUIDELINES AND CRITERIA FOR THE SEARCH STRATEGY, EVALUATION, SELECTION, AND DOCUMENTATION OF KEY DATA AND SUPPORTING… -- 2.3.1 Search Strategy -- 2.3.2 Evaluation, Selection, and Documentation of Key and Supporting Data -- 2.3.3 Elements for Discussion on Data Adequacy and Research Needs -- 2.4 DOSIMETRY CORRECTIONS FROM ANIMAL TO HUMAN EXPOSURES -- 2.4.1 Discussion of Potential Dosimetry Correction Methodologies for Gases -- 2.4.1.1 The Respiratory System As a Target Organ -- 2.4.1.2 Systemic Toxicity -- 2.4.2 Current Approach of the NAC/AEGL Committee to Dosimetry Corrections -- 2.5 GUIDELINES AND CRITERIA FOR SELECTION OF UNCERTAINTY FACTORS TO ADDRESS THE VARIABILITY BETWEEN ANIMALS AND HUMANS AND… -- 2.5.1 Introduction -- 2.5.2 Background -- 2.5.3 Considerations and Approaches to the Selection of UFs for Developing AEGLs -- 2.5.3.1 Interspecies UFs-Use in the Development of AEGL Values-Discussion -- 2.5.3.2 Interspecies UFs-NAC/AEGL Committee Guidelines -- 2.5.3.2.1 Small Interspecies Variability or Most Appropriate Species Used -- 2.5.3.2.2 Most Susceptible Species Not Used -- 2.5.3.2.3 Mechanism or Mode of Action Is Unlikely to Differ Among Species -- 2.5.3.2.4 Mechanism or Mode of Action Is Unknown -- 2.5.3.2.5 Large Variability in Response Between Species.

2.5.3.2.6 Humans More Susceptible Than Animals -- 2.5.3.2.7 Inadequate Data -- 2.5.3.2.8 A Selected UF Applied to Animal Data Driving the AEGL-2 or -3 to a Value Tolerated by Humans Without Lethal or… -- 2.5.3.2.9 A Multiple Exposure Study Used to Set the Level -- 2.5.3.2.10 Selection of the NOAEL -- 2.5.3.3 Intraspecies UFs Used in the Development of AEGL Values-Discussion -- 2.5.3.3.1 Range of Susceptibility -- 2.5.3.3.2 Selection of Intraspecies UFs -- 2.5.3.3.3 Distinguishing Susceptible and Hypersusceptible Subpopulations -- 2.5.3.3.4 Estimating the Range of Variability in a Human Population -- 2.5.3.4 Intraspecies UFs-NAC/AEGL Guidelines -- 2.5.3.4.1 Toxic Effect Is Less Severe Than Defined for the AEGL Tier -- 2.5.3.4.2 Susceptible Individuals Used -- 2.5.3.4.3 Age, Life Stage, and Physical Condition Differences -- 2.5.3.4.4 Response of Normal and Susceptible Individuals to Chemical Exposure is Unlikely to Differ for Mechanistic Reasons -- 2.5.3.4.5 Mode or Mechanism of Action Is Unknown -- 2.5.3.4.6 UFs That Result in AEGL Values That Conflict with Actual Human Exposure Data -- 2.6 GUIDELINES AND CRITERIA FOR SELECTION OF MODIFYING FACTORS -- 2.6.1 Definition -- 2.6.2 Use of Modifying Factors to Date in the Preparation of AEGL Values -- 2.7 GUIDELINES AND CRITERIA FOR TIME SCALING -- 2.7.1 Overview -- 2.7.2 Summary of Key Publications on Time Scaling -- 2.7.3 Summary of the Approaches That May Be Taken for Time Scaling -- 2.7.4 Use of Empirical Data Available for AEGL-Specified Exposure Durations -- 2.7.5 Derivation of Values of n When Adequate Empirical Data Are Available for Durations Other Than the AEGL-… -- 2.7.5.1 Selection of Appropriate Health-Effect Endpoint for Deriving a Value for n -- 2.7.5.2 Criteria for Adequate Empirical Data for Deriving Values of n -- 2.7.5.3 Curve Fitting and Statistical Testing of the Generated Curve.

2.7.5.4 Examples of NAC/AEGL Committee Derivations of Values of n from Empirical Data -- 2.7.6 Selection of Values of n When Adequate Empirical Data Are Not Available to Derive Values for n -- 2.7.6.1 Selection of Values of n When Extrapolating from Shorter to Longer Exposure Durations -- 2.7.6.2 Selection of Values of n When Extrapolating from Longer to Shorter Exposure Durations -- 2.7.7 Special Considerations in the Time Scaling of AEGL-1 and AEGL-2 Values -- 2.7.8 Time Scaling-Guidelines for the NAC/AEGL Committee Approach -- 2.7.8.1 Use of Empirical Data to Determine the Exposure Concentration-Exposure Duration Relationship -- 2.7.8.2 Estimating the Exposure Concentration-Exposure Duration Relationship Using a Structurally Related Material -- 2.7.8.3 Estimating the Exposure Concentration-Exposure Duration Relationship When Data Are Not Available to Derive a Value… -- 2.7.8.4 Determining Exposure Concentration-Exposure Duration Relationships When Data Are Not Available to Derive a Value… -- 2.7.8.5 AEGL Exposure Values Are Constant Across Time -- 2.8 GUIDELINES AND CRITERIA FOR ADDRESSING SHORT-TERM EXPOSURE TO KNOWN AND SUSPECT CARCINOGENS -- 2.8.1 NRC Guidance -- 2.8.2 Precedents for Developing Short-Term Exposure Limits Based on Carcinogenicity -- 2.8.3 Scientific Basis for Credible Theoretical Excess Carcinogenic Risk Assessments for Single Exposures of 8… -- 2.8.4 Practical Issues of Using Quantitative, Carcinogenic Risk Assessments for Developing AEGLs -- 2.8.5 Current Approach of the NAC/AEGL Committee to Assessing Potential Single Exposure Carcinogenic Risks -- 2.8.5.1 Evaluation of Carcinogenicity Data -- 2.8.5.2 Methodology Used for Assessing the Carcinogenic Risk of a Single Exposure -- 2.8.5.2.1 Determination of an Adjustment Factor for the Dose-Dependent Stage of Carcinogenesis.

2.8.5.3 Summary of Cancer-Assessment Methodology Used by the NAC/AEGL Committee -- 2.9 GUIDELINES AND CRITERIA FOR MISCELLANEOUS PROCEDURES AND METHODS -- 2.9.1 Mathematical Rounding of AEGL Values -- 2.9.2 Multiplication of UFs -- 2.9.3 Conversion Between Parts per Million and Milligrams per Cubic Meter -- 3. Format and Content of Technical Support Documents -- EDITORIAL CONVENTIONS -- 3.1 FORMAT AND CONTENT OF TECHNICAL SUPPORT DOCUMENTS -- Preface -- Table of Contents -- Summary -- Outline of the Main Body of the Technical Support Document -- 3.2 GRAPHIC DESCRIPTION OF DATA -- 4. Current Administrative Processes and Procedures for the Development of AEGL Values -- 4.1 COMMITTEE MEMBERSHIP AND ORGANIZATIONAL STRUCTURE -- 4.2 THE AEGL DEVELOPMENT AND PEER-REVIEW PROCESS -- Stage 1: Draft AEGLs -- Stage 2: Proposed AEGLs -- Stage 3: Interim AEGLs -- Stage 4: Final AEGLs -- 4.3 OPERATION OF THE NAC/AEGL COMMITTEE -- 4.4 ROLE OF THE DIRECTOR OF THE AEGL PROGRAM -- 4.5 ROLE OF THE DESIGNATED FEDERAL OFFICER -- 4.6 ROLE OF THE NAC/AEGL COMMITTEE CHAIR -- 4.7 CLASSIFICATION OF THE STATUS OF AEGL VALUES -- 4.8 FUNCTION OF AEGL DEVELOPMENT TEAMS -- 4.8.1 Role of a Chemical Manager -- 4.8.2 Role of a Chemical Reviewer -- 4.8.3 Role of a Staff Scientist at the Organization That Drafts TSDs -- 4.9 ROLE OF NAC/AEGL COMMITTEE MEMBERS -- 4.10 ROLE OF THE ORGANIZATION THAT DRAFTS TSDS -- References -- Appendixes -- Appendix A Priority Lists of Chemicals -- INITIAL LIST OF 85 PRIORITY CHEMICALS FOR AEGL DEVELOPMENT -- Organization Lists Used to Compile the Master List and The Initial List of 85 Priority Chemicals -- Appendix B Diagram of the AEGL Development Process -- Appendix C Glossary of Acronyms, Abbreviations, and Symbols -- Appendix D Example of a Table of Contents of A Technical Support Document -- TABLE OF CONTENTS.

Appendix E Example of a Summary of A Technical Support Document.