1 Interim: 10/2008 2 3 4 United States Environmental Protection Agency 5 Office of Pollution Prevention and Toxics 6 7 8 9 10 11 12 13 14 METHYL METHACRYLATE 15 (CAS Reg. No. 80-62-6) 16 17 18 19 20 21 22 INTERIM ACUTE EXPOSURE GUIDELINE LEVELS 23 (AEGLs) 24 25 1 Interim: 10/2008 2 3 4 5 6 METHYL METHACRYLATE 7 (CAS Reg. No. 80-62-6) 8 9 10 11 12 INTERIM ACUTE EXPOSURE GUIDELINE LEVELS 13 (AEGLs) 14 METHYL METHACRYLATE Interim: 10/2008; Page 3 of 73 1 PREFACE 2 3 Under the authority of the Federal Advisory Committee Act (FACA) P. L. 92-463 of 4 1972, the National Advisory Committee for Acute Exposure Guideline Levels for Hazardous 5 Substances (NAC/AEGL Committee) has been established to identify, review and interpret 6 relevant toxicologic and other scientific data and develop AEGLs for high priority, acutely 7 toxic chemicals. 8 9 AEGLs represent threshold exposure limits for the general public and are applicable 10 to emergency exposure periods ranging from 10 minutes to 8 hours. Three levels – AEGL-1, 11 AEGL-2 and AEGL-3 - are developed for each of five exposure periods (10 and 30 minutes, 12 1 hour, 4 hours, and 8 hours) and are distinguished by varying degrees of severity of toxic 13 effects. The three AEGLs are defined as follows: 14 15 AEGL-1 is the airborne concentration (expressed as parts per million or milligrams 16 per cubic meter [ppm or mg/m3]) of a substance above which it is predicted that the general 17 population, including susceptible individuals, could experience notable discomfort, irritation, 18 or certain asymptomatic, non-sensory effects. However, the effects are not disabling and are 19 transient and reversible upon cessation of exposure. 20 21 AEGL-2 is the airborne concentration (expressed as ppm or mg/m3) of a substance 22 above which it is predicted that the general population, including susceptible individuals, 23 could experience irreversible or other serious, long-lasting adverse health effects or an 24 impaired ability to escape. 25 26 AEGL-3 is the airborne concentration (expressed as ppm or mg/m3) of a substance 27 above which it is predicted that the general population, including susceptible individuals, 28 could experience life-threatening health effects or death. 29 30 Airborne concentrations below the AEGL-1 represent exposure levels that could 31 produce mild and progressively increasing but transient and nondisabling odor, taste, and 32 sensory irritation or certain asymptomatic, non-sensory effects. With increasing airborne 33 concentrations above each AEGL, there is a progressive increase in the likelihood of 34 occurrence and the severity of effects described for each corresponding AEGL. Although the 35 AEGL values represent threshold levels for the general public, including susceptible 36 subpopulations, such as infants, children, the elderly, persons with asthma, and those with 37 other illnesses, it is recognized that individuals, subject to unique or idiosyncratic responses, 38 could experience the effects described at concentrations below the corresponding AEGL. 39 METHYL METHACRYLATE Interim: 10/2008; Page 4 of 73 1 TABLE OF CONTENTS 2 3 PREFACE...............................................................................................................................................3 4 LIST OF TABLES..................................................................................................................................6 5 LIST OF FIGURES ................................................................................................................................6 6 EXECUTIVE SUMMARY.....................................................................................................................7 7 1. INTRODUCTION........................................................................................................................11 8 2. HUMAN TOXICITY DATA.......................................................................................................12 9 2.1. Acute Lethality....................................................................................................................12 10 2.2. Nonlethal Toxicity...............................................................................................................12 11 2.2.1. Case Reports....................................................................................................................12 12 2.2.2. Epidemiologic Studies and Volunteer Studies ................................................................13 13 2.3. Genotoxicity and Cytotoxicity ............................................................................................16 14 2.4. Carcinogenicity....................................................................................................................16 15 2.5. Summary..............................................................................................................................17 16 3. ANIMAL TOXICITY DATA......................................................................................................18 17 3.1. Acute Lethality....................................................................................................................18 18 3.1.1 Non-human Primates.......................................................................................................18 19 3.1.2. Dogs ................................................................................................................................18 20 3.1.3. Rats..................................................................................................................................19 21 3.1.4. Mice.................................................................................................................................21 22 3.1.5 Guinea Pigs.....................................................................................................................22 23 3.1.6 Rabbits.............................................................................................................................22 24 3.2. Nonlethal Toxicity...............................................................................................................25 25 3.2.1. Dogs ................................................................................................................................25 26 3.2.2. Rats..................................................................................................................................26 27 3.2.3. Mice.................................................................................................................................29 28 3.2.4. Guinea Pigs.....................................................................................................................29 29 3.2.5. Rabbits.............................................................................................................................29 30 3.3. Repeated Exposure ..............................................................................................................31 31 3.4. Skin Sensitization ................................................................................................................32 32 3.5. Mutagenicity and Genotoxicity ...........................................................................................33 33 3.6. Carcinogenicity....................................................................................................................33 34 3.7. Summary..............................................................................................................................33 35 4. SPECIAL CONSIDERATIONS..................................................................................................35 36 4.1. Metabolism and Disposition................................................................................................35 37 4.2. Mechanism of Toxicity........................................................................................................38 38 4.3. Structure Activity Relationships..........................................................................................39 39 4.4. Other Relevant Information.................................................................................................40 40 4.4.1. Species Variability..........................................................................................................40 41 4.4.2. Susceptible Populations ..................................................................................................41 42 4.4.3. Concentration-Exposure Duration Relationship .............................................................41 43 5. DATA ANALYSIS FOR AEGL-1 ..............................................................................................41 44 5.1. Summary of Human Data Relevant to AEGL-1..................................................................41 45 5.2. Summary of Animal Data Relevant to AEGL-1..................................................................42 46 5.3. Derivation of AEGL-1.........................................................................................................42 47 6. DATA ANALYSIS FOR AEGL-2 ..............................................................................................43 METHYL METHACRYLATE Interim: 10/2008; Page 5 of 73 1 6.1. Summary of Human Data Relevant to AEGL-2..................................................................43 2 6.2. Summary of Animal Data Relevant to AEGL-2..................................................................43