(Aegls) for TRIMETHYL PHOSPHITE CAS Reg. No. 121-45-9
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ACUTE EXPOSURE GUIDELINE LEVELS (AEGLs) FOR TRIMETHYL PHOSPHITE CAS Reg. No. 121-45-9 INTERIM TRIMETHYL PHOSPHITE Interim: Sep-2010 1 2 ACUTE EXPOSURE GUIDELINE LEVELS (AEGLs) 3 FOR 4 TRIMETHYL PHOSPHITE 5 CAS Reg. No. 121-45-9 6 7 8 9 PROPOSED 10 11 12 13 14 15 16 17 18 19 20 21 2 TRIMETHYL PHOSPHITE Interim: Sep-2010 1 2 3 PREFACE 4 5 Under the authority of the Federal Advisory Committee Act (FACA) P. L. 92-463 of 6 1972, the National Advisory Committee for Acute Exposure Guideline Levels for Hazardous 7 Substances (NAC/AEGL Committee) has been established to identify, review and interpret 8 relevant toxicologic and other scientific data and develop AEGLs for high priority, acutely toxic 9 chemicals. 10 11 AEGLs represent threshold exposure limits for the general public and are applicable to 12emergency exposure periods ranging from 10 minutes to 8 hours. Three levels C AEGL-1, 13AEGL-2 and AEGL-3 C are developed for each of five exposure periods (10 and 30 minutes, 1 14 hour, 4 hours, and 8 hours) and are distinguished by varying degrees of severity of toxic effects. 15 The three AEGLs are defined as follows: 16 17 AEGL-1 is the airborne concentration (expressed as parts per million or milligrams per 18 cubic meter [ppm or mg/m3]) of a substance above which it is predicted that the general 19 population, including susceptible individuals, could experience notable discomfort, irritation, or 20 certain asymptomatic, non-sensory effects. However, the effects are not disabling and are 21 transient and reversible upon cessation of exposure. 22 23 AEGL-2 is the airborne concentration (expressed as ppm or mg/m3) of a substance above 24 which it is predicted that the general population, including susceptible individuals, could 25 experience irreversible or other serious, long-lasting adverse health effects or an impaired ability 26 to escape. 27 28 AEGL-3 is the airborne concentration (expressed as ppm or mg/m3) of a substance above 29 which it is predicted that the general population, including susceptible individuals, could 30 experience life-threatening health effects or death. 31 32 Airborne concentrations below the AEGL-1 represent exposure levels that could produce 33 mild and progressively increasing but transient and nondisabling odor, taste, and sensory 34 irritation or certain asymptomatic, non-sensory effects. With increasing airborne concentrations 35 above each AEGL, there is a progressive increase in the likelihood of occurrence and the severity 36 of effects described for each corresponding AEGL. Although the AEGL values represent 37 threshold levels for the general public, including susceptible subpopulations, such as infants, 38 children, the elderly, persons with asthma, and those with other illnesses, it is recognized that 39 individuals, subject to unique or idiosyncratic responses, could experience the effects described 40 at concentrations below the corresponding AEGL 41 42 3 TRIMETHYL PHOSPHITE Interim: Sep-2010 1 TABLE OF CONTENTS 2 PREFACE .............................................................................................................................................3 3 EXECUTIVE SUMMARY ...................................................................................................................6 4 1. INTRODUCTION.........................................................................................................................8 5 2. HUMAN TOXICITY DATA ........................................................................................................8 6 2.1. Acute Lethality..........................................................................................................................8 7 2.2. Nonlethal Toxicity.....................................................................................................................8 8 2.2.1. Odor Threshold/Odor Awareness....................................................................................8 9 2.2.2. Case Reports.....................................................................................................................9 10 2.3. Developmental/Reproductive Toxicity .....................................................................................9 11 2.4. Genotoxicity ..............................................................................................................................9 12 2.5. Carcinogenicity .........................................................................................................................9 13 2.6. Summary...................................................................................................................................9 14 3. ANIMAL TOXICITY DATA .......................................................................................................9 15 3.1. Acute Lethality..........................................................................................................................9 16 3.2. Repeated-Exposure Studies ....................................................................................................10 17 3.3. Developmental/Reproductive Toxicity ...................................................................................11 18 3.4. Genotoxicity ............................................................................................................................11 19 3.5. Chronic Toxicity/Carcinogenicity ..........................................................................................12 20 3.6. Summary.................................................................................................................................12 21 4. SPECIAL CONSIDERATIONS.................................................................................................12 22 4.1. Metabolism and Disposition ...................................................................................................12 23 4.2. Mechanism of Toxicity............................................................................................................12 24 4.3. Structure Activity Relationships ............................................................................................12 25 4.4. Other Relevant Information...................................................................................................12 26 4.4.1. Species Variability..........................................................................................................13 27 4.4.2. Susceptible Populations..................................................................................................13 28 4.4.3. Concentration-Exposure Duration Relationship...........................................................13 29 4.4.4. Concurrent Exposure Issues ..........................................................................................13 30 5. DATA ANALYSIS FOR AEGL-1 ..............................................................................................13 31 5.1. Summary of Human Data Relevant to AEGL-1 ....................................................................13 32 5.2. Summary of Animal Data Relevant to AEGL-1 ....................................................................13 33 5.3. Derivation of AEGL-1.............................................................................................................13 34 6. DATA ANALYSIS FOR AEGL-2 ..............................................................................................14 35 6.1. Summary of Human Data Relevant to AEGL-2 ....................................................................14 36 6.2. Summary of Animal Data Relevant to AEGL-2 ....................................................................14 37 6.3. Derivation of AEGL-2.............................................................................................................14 38 7. DATA ANALYSIS FOR AEGL-3 ..............................................................................................15 39 7.1. Summary of Human Data Relevant to AEGL-3 ....................................................................15 40 7.2. Summary of Animal Data Relevant to AEGL-3 ....................................................................15 41 7.3. Derivation of AEGL-3.............................................................................................................15 42 8. SUMMARY OF AEGLS.............................................................................................................15 43 8.1. AEGL Values and Toxicity Endpoints ...................................................................................15 44 8.2. Comparison with Other Standards and Guidelines...............................................................16 45 8.3. Data Adequacy and Research.................................................................................................16 46 9. REFERENCES............................................................................................................................17 47 APPENDIX A: DERIVATION OF AEGL VALUES........................................................................19 48 APPENDIX B: DERIVATION SUMMARY FOR TRIMETHYL PHOSPHITE AEGLS ..............22 49 APPENDIX C: CATEGORY PLOT FOR TRIMETHYL PHOSPHITE................................................25 4 TRIMETHYL PHOSPHITE Interim: Sep-2010 1 LIST OF TABLES 2 3 Table 1. Summary of AEGL Values for Trimethyl Phosphite ................................................ 7 4 Table 2. Chemical and physical properties for trimethyl phosphite.....................................