INTERIM 1: 6\2000 1,1,1-TRICHLOROETHANE CAS REG. NO. 71-55-06 INTERIM ACUTE EXPOSURE GUIDELINE LEVELS (AEGLs) For NAS/COT Subcommittee for AEGLs June 2000 INTERIM 1: 6/2000 INTERIM ACUTE EXPOSURE GUIDELINE LEVELS (AEGLs) 1,1,1-TRICHLOROETHANE CAS REG. NO. 71-55-06 Oak Ridge National Laboratory, Managed and Operated by UT-Battelle, LLC, for the U.S. Department of Energy under contract number DE-AC05-00OR22725. 1,1,1-TRICHLOROETHANE INTERIM 1: 6\2000 1 2 PREFACE 3 4 Under the authority of the Federal Advisory Committee Act (FACA) P. L. 92-463 of 1972, 5 the National Advisory Committee for Acute Exposure Guideline Levels for Hazardous 6 Substances (NAC/AEGL Committee) has been established to identify, review and interpret 7 relevant toxicologic and other scientific data and develop AEGLs for high priority, acutely toxic 8 chemicals. 9 10 AEGLs represent threshold exposure limits for the general public and are applicable to 11 emergency exposure periods ranging from 10 minutes to 8 hours. AEGL-2 and AEGL-3 levels, 12 and AEGL-1 levels as appropriate, will be developed for each of five exposure periods (10 and 13 30 minutes, 1 hour, 4 hours, and 8 hours) and will be distinguished by varying degrees of 14 severity of toxic effects. It is believed that the recommended exposure levels are applicable to 15 the general population including infants and children, and other individuals who may be 16 sensitive and susceptible. The three AEGLs have been defined as follows: 17 18 AEGL-1 is the airborne concentration (expressed as ppm or mg/m3) of a substance above 19 which it is predicted that the general population, including susceptible individuals, could 20 experience notable discomfort, irritation, or certain asymptomatic, non-sensory effects. 21 However, the effects are not disabling and are transient and reversible upon cessation of 22 exposure. 23 24 AEGL-2 is the airborne concentration (expressed as ppm or mg/m3) of a substance above 25 which it is predicted that the general population, including susceptible individuals, could 26 experience irreversible or other serious, long-lasting adverse health effects, or an impaired 27 ability to escape. 28 29 AEGL-3 is the airborne concentration (expressed as ppm or mg/m3) of a substance above 30 which it is predicted that the general population, including susceptible individuals, could 31 experience life-threatening health effects or death. 32 33 Airborne concentrations below the AEGL-1 represent exposure levels that could produce 34 mild and progressively increasing odor, taste, and sensory irritation, or certain non-symptomatic, 35 non-sensory effects. With increasing airborne concentrations above each AEGL level, there is a 36 progressive increase in the likelihood of occurrence and the severity of effects described for each 37 corresponding AEGL level. Although the AEGL values represent threshold levels for the 38 general public, including sensitive subpopulations, it is recognized that certain individuals, 39 subject to unique or idiosyncratic responses, could experience the effects described at 40 concentrations below the corresponding AEGL level. 41 3 1,1,1-TRICHLOROETHANE INTERIM 1: 6\2000 1 TABLE OF CONTENTS 2 3 4 PREFACE ...................................................................3 5 6 LIST OF TABLES.............................................................4 7 8 EXECUTIVE SUMMARY......................................................7 9 10 1. INTRODUCTION .........................................................10 11 12 2. HUMAN TOXICITY DATA ................................................11 13 2.1. Acute Lethality ........................................................11 14 2.1.1. Case Reports ....................................................11 15 2.1.2. Epidemiologic Studies .............................................13 16 2.2. Nonlethal Toxicity .....................................................13 17 2.2.1. Case Reports ....................................................13 18 2.2.2. Occupational Exposures ...........................................14 19 2.2.3. Experimental Studies ..............................................15 20 2.3. Developmental/Reproductive Toxicity .....................................19 21 2.4. Genotoxicity ..........................................................19 22 2.5. Carcinogenicity .......................................................19 23 2.6. Summary.............................................................20 24 25 3. ANIMAL TOXICITY DATA................................................20 26 3.1. Acute Lethality ........................................................20 27 3.1.1. Rats ...........................................................20 28 3.1.2. Mice ...........................................................21 29 3.2. Nonlethal Toxicity .....................................................22 30 3.2.1. Nonhuman Primates ...............................................22 31 3.2.2. Dogs ...........................................................23 32 3.2.3. Rats ...........................................................24 33 3.2.4. Mice ...........................................................24 34 3.2.5. Rabbits .........................................................26 35 3.2.6. Guinea pigs .....................................................27 36 3.3. Developmental/Reproductive Toxicity .....................................27 37 3.4. Genotoxicity ..........................................................29 38 3.5. Carcinogenicity .......................................................29 39 3.6. Summary.............................................................29 40 41 4. SPECIAL CONSIDERATIONS..............................................30 42 4.1. Metabolism and Disposition ..............................................30 43 4.2. Mechanism of Toxicity .................................................31 44 4.3. Structure-Activity Relationships ..........................................32 45 4.4. Other Relevant Information ..............................................32 46 TABLE OF CONTENTS (Continued) 47 4 1,1,1-TRICHLOROETHANE INTERIM 1: 6\2000 1 4.4.1. Species Variability ................................................32 2 4.4.2. Susceptible Subpopulations .........................................33 3 4.4.3. Concentration-Response Relationship .................................33 4 5 5. DATA ANALYSIS FOR AEGL-1 ............................................34 6 5.1. Summary of Human Data Relevant to AEGL-1 ...............................34 7 5.2. Summary of Animal Data Relevant to AEGL-1 ..............................34 8 5.3. Derivation of AEGL-1 ..................................................35 9 10 6. DATA ANALYSIS FOR AEGL-2 ............................................35 11 6.1. Summary of Human Data Relevant to AEGL-2 ...............................35 12 6.2. Summary of Animal Data Relevant to AEGL-2 ..............................36 13 6.3. Derivation of AEGL-2 ..................................................36 14 15 7. DATA ANALYSIS FOR AEGL-3 ............................................37 16 7.1. Summary of Human Data Relevant to AEGL-3 ...............................37 17 7.2. Summary of Animal Data Relevant to AEGL-3 ..............................37 18 7.3. Derivation of AEGL-3 ..................................................37 19 20 8. SUMMARY OF PROPOSED AEGLS.........................................38 21 8.1. AEGL Values and Toxicity Endpoints ......................................38 22 8.2. Comparison with Other Standards and Guidelines ............................39 23 8.3. Data Quality and Research Needs .........................................40 24 25 9. REFERENCES ...........................................................41 26 27 APPENDIX A: Time-Scaling Calculations for 1,1,1-Trichloroethane ...................52 28 29 APPENDIX B: Derivation of AEGL Values.......................................55 30 31 APPENDIX C: Derivation Summary for 1,1,1-Trichloroethane AEGLs .................59 32 5 1,1,1-TRICHLOROETHANE INTERIM 1: 6\2000 1 LIST OF TABLES 2 3 Summary of Interim Values for 1,1,1-Trichloroethane .................................8 4 1. Chemical and Physical Data..................................................11 5 2. Effects of Exposure to 1,1,1-Trichloroethane in Humans ...........................17 6 3. Summary of Animal LC50 Toxicity Data With 1,1,1-Trichloroethane .................22 7 4. Summary of Animal Neurobehavioral Data with 1,1,1-Trichloroethane ...............25 8 5. AEGL-1 Values for 1,1,1-Trichloroethane .......................................35 9 6. AEGL-2 Values for 1,1,1-Trichloroethane .......................................37 10 7. AEGL-3 Values for 1,1,1-Trichloroethane .......................................38 11 8. Summary of AEGL Values...................................................38 12 9. Extant Standards and Guidelines for 1,1,1-Trichloroethane ..........................40 13 14 15 16 FIGURE 17 18 1. AEGL Values and Support Data for 1,1,1-Trichloroethane ..........................39 19 20 6 1,1,1-TRICHLOROETHANE INTERIM 1: 6\2000 1 EXECUTIVE SUMMARY 2 3 1,1,1-Trichloroethane is a colorless, nonflammable liquid used primarily as an industrial 4 metal degreasing agent. It is also used as a solvent for adhesives, inks, and coatings and as an 5 aerosol propellant (Kirk-Othmer, 1991; WHO, 1992). Solvent vapor is readily absorbed from 6 the respiratory tract and distributed throughout the body, accumulating in tissues with high lipid 7 content.