TSCA Work Plan Chemical Risk Assessment - N …

1 TSCA work plan Chemical Risk Assessment N-Methylpyrrolidone: Paint Stripper Use CASRN: 872-50-4 March 2015 NOUnited states environmental protection agency EPA Document# 740-R1-5002 March 2015 Office of Chemical Safety and Pollution Prevention TABLE OF CONTENTS TABLE OF CONTENTS .. 2 AUTHORS / CONTRIBUTORS / ACKNOWLEDGEMENTS / REVIEWERS .. 9 ABBREVIATIONS .. 11 EXECUTIVE SUMMARY .. 14 1 BACKGROUND AND SCOPE .. 20 INTRODUCTION .. 20 USES AND PRODUCTION VOLUMES .. 21 Assessment and Regulatory History .. 21 Scope of the Assessment .. 23 PROBLEM FORMULATION .. 23 Physical and Chemical Properties .. 24 environmental Fate .. 25 Conceptual Model .. 26 Exposure Pathways .. 26 Health Effects and Human Receptors .. 27 Analysis plan .. 28 2 EXPOSURE Assessment .. 30 OCCUPATIONAL EXPOSURES .. 30 Approach and Methodology .. 30 Identification of Relevant Industries .. 31 Approach for Determining Occupational Exposure Data and Input Parameters for PBPK Modeling.

2 31 Estimates of Occupational Exposure Parameters and Number of Exposed Workers .. 32 Use of Occupational Exposure Estimates in PBPK Modeling .. 35 CONSUMER EXPOSURES .. 37 Approach and Methodology .. 37 Consumer Dermal Exposure Assessment .. 38 Consumer Users and Residential Non-Users Inhalation Exposure 38 Model Outputs and Exposure Calculations .. 46 Use of Consumer Exposure Estimates in PBPK Modeling .. 46 3 HAZARD IDENTIFICATION AND DOSE-RESPONSE .. 48 APPROACH AND METHODOLOGY .. 48 Selection of Peer-Reviewed Assessments for Hazard Identification and Dose-Response Analysis .. 48 Hazard Summary and Hazard Identification .. 49 Selection of Developmental Toxicity Studies and Endpoints .. 60 Decreased Fetal and Postnatal Body Weights .. 63 Resorptions and Fetal Mortality .. 65 Other Fetal Effects .. 66 Conclusions and Selection of Key Endpoints .. 67 DOSE-RESPONSE Assessment AND STUDY SELECTION.

3 68 Identification of Studies for BMD Modeling .. 68 Derivation of Internal Doses .. 69 PODs for Acute Exposure .. 73 PODs for Chronic Exposure .. 76 Page 2 of 281 Considerations for Sensitive Subpopulations and Lifestages .. 78 4 HUMAN HEALTH RISK CHARACTERIZATION .. 80 RISK ESTIMATION APPROACH FOR ACUTE AND CHRONIC EXPOSURES .. 80 Risk Estimates for Acute Occupational Exposure to NMP .. 82 Risk Estimates for Acute Consumer Exposure to NMP .. 87 Risk Estimates for Chronic Occupational Exposures to 90 HUMAN HEALTH RISK CHARACTERIZATION SUMMARY .. 94 KEY SOURCES OF UNCERTAINTY AND DATA LIMITATIONS .. 95 Key Uncertainties in the Occupational Exposure Assessment .. 95 Key Uncertainties in the Consumer Exposure Assessment .. 96 Key Uncertainties in the Hazard and Dose-Response Assessments .. 99 Key Uncertainties in the Risk Assessment .. 101 RISK Assessment CONCLUSIONS .. 103 REFERENCES.

4 106 APPENDICES .. 120 Appendix A environmental EFFECTS SUMMARY .. 121 A-1 ACUTE TOXICITY TO AQUATIC ORGANISMS .. 121 A-2 CHRONIC TOXICITY TO AQUATIC ORGANISMS .. 123 A-3 TOXICITY TO SEDIMENT AND SOIL ORGANISMS .. 123 A-4 TOXICITY TO WILDLIFE .. 123 A-5 SUMMARY OF environmental HAZARD 124 Appendix B Chemical REPORTING DATA .. 125 B-1 CONSUMER USES .. 127 B-2 PAINT STRIPPING APPLICATIONS .. 128 Appendix C STATE NMP REGULATIONS .. 129 Appendix D OCCUPATIONAL EXPOSURE Assessment SUPPORT INFORMATION .. 130 D-1 SUMMARY OF DERMAL EXPOSURE PARAMETERS, INHALATION CONCENTRATIONS AND EXPOSURE REDUCTION FACTORS .. 130 D-2 DATA NEEDS AND DATA COLLECTION .. 130 D-3 INDUSTRIES THAT EMPLOY PAINT STRIPPING ACTIVITIES .. 133 D-4 OCCUPATIONAL PAINT STRIPPING PROCESSES AND ASSOCIATED WORKER ACTIVITIES .. 134 D-5 FACILITY AND POPULATION DATA AND INFORMATION .. 139 D-6 DERMAL EXPOSURE 144 D-7 OCCUPATIONAL INHALATION EXPOSURE LITERATURE DATA.

5 146 Appendix E CONSUMER EXPOSURE Assessment .. 153 E-1 ESTIMATION OF EMISSION PROFILES FOR PAINT REMOVERS/STRIPPERS .. 153 E-2 SENSITIVITY ANALYSIS FOR INHALATION SCENARIOS .. 165 E-3 INHALATION EXPOSURE SCENARIO INPUTS .. 166 E-4 INHALATION MODEL OUTPUTS AND EXPOSURE CALCULATIONS .. 177 E-5 MCCEM INHALATION MODELING CASE 185 E-5-1 NMP Scenario 1. Coffee Table, Brush-On, Workshop, User in ROH during wait time, ACH, Weight 185 E-5-2 NMP Scenario 2. Coffee Table, Brush-On, Workshop, User in Workshop during wait time, ACH, Weight Fraction .. 188 E-5-3 NMP Scnario 3. Chest, Brush-On, Workshop, User in ROH during wait time, ACH, Weight Fraction .. 191 Page 3 of 281 E-5-4 NMP Scenario 4. Bathtub, Brush-On, Bathroom + Source Cloud, User in ROH during wait time, ACH, Weight Fraction .. 194 E-5-5 NMP Scenario 5. Bathtub, Brush-On, Bathroom + Source Cloud, User in ROH during wait time, ACH, Weight Fraction.

6 197 E-5-6 NMP Scenario 6a. Coffee Table, Spray-On, Workshop, User in workshop during wait time, ACH, Weight Fraction .. 200 E-5-7 New Scenario 6b. Coffee Table, Spray-On, Workshop, User in workshop during wait time, ACH, Weight Fraction .. 203 E-5-8 NMP Scenario 7a Chest, Spray-On, Workshop, User in ROH during wait time, ACH, Weight 206 E-5-9 NMP Scenario 7b Chest, Spray-On, Workshop, User in ROH during wait time, ACH, Weight 209 Appendix F TOXICOLOGY STUDIES .. 212 F-1 LITERATURE COLLECTION .. 212 F-2 STUDY QUALITY AND SELECTION CONSIDERATIONS .. 212 F-3 DEVELOPMENTAL TOXICITY STUDIES CONSIDERED FOR USE IN RISK Assessment .. 214 F-3-1 Oral Toxicity Studies .. 214 F-3-2 Inhalation Toxicity Studies .. 218 F-3-3 Dermal Toxicity Studies .. 221 F-4 HUMAN CASE REPORT .. 221 Appendix G HUMAN EXPOSURE STUDIES .. 223 G-1 REVIEW OF AKKESON ET AL., 2004 .. 224 G-2 REVIEW OF AKKESON AND JONSSON, 2000 .. 225 G-3 REVIEW OF AKESSON AND PAULSSON, 1997.

7 226 G-4 REVIEW OF BADER ET AL., 2005 .. 227 G-5 REVIEW OF BADER AND VAN THRIEL, 2006 .. 228 G-6 REVIEW OF BADER ET AL., 2007 .. 229 G-7 REVIEW OF BADER ET AL., 2008 .. 230 G-8 REVIEW OF XIAOFEI ET AL., 2000 .. 231 Appendix H BENCHMARK DOSE ANALYSIS .. 232 H-1 BENCHMARK DOSE MODELING OF FETAL/PUP BODY WEIGHT CHANGES FOR CHRONIC EXPOSURES .. 232 H-1-1 Results for Saillenfait et al., 2003 .. 234 H-1-2 Results for Saillenfait et al., 2002 .. 237 H-1-3 Results for Saillenfait et al., 2002 and 2003 combined .. 240 H-1-4 Results for DuPont, 1990 .. 243 H-1-5 Results for Becci et al., 1982 .. 246 H-2 BENCHMARK DOSE MODELING OF EFFECTS FOR ACUTE EXPOSURES .. 248 H-2-1 Results for Saillenfait et al., 2002 and 2003 combined using Cmax .. 249 H-2-2 Results for Saillenfait et al., 2002 and 2003 combined using AUC .. 252 H-2-3 Results for Sitarek et al., 255 Appendix I PBPK MODELING .. 256 I-1 RAT MODEL .. 256 I-2 HUMAN 263 I-2-1 Corrections to Human Model Structure.

8 264 LIST OF TABLES Table 1-1 Physical and Chemical Properties of NMP .. 24 Table 1-2 environmental Fate Characteristics of NMP .. 26 Page 4 of 281 Table 2-1 Summary of Parameters for Worker Dermal Exposure to Liquidsa .. 33 Table 2-2 Summary of Parameters for Worker Inhalation Exposure Concentrationsa .. 34 Table 2-3 Workplace Exposure Scenario Characteristics .. 36 Table 2-4 NMP Exposure Scenarios for Characterizing Consumer Inhalation Exposures .. 44 Table 2-5 NMP Consumer Paint Stripping Scenario Descriptions and Parameters .. 47 Table 3-1 Summary of Studies with Reproductive or Developmental Effects .. 52 Table 3-2 Summary of Exposure Pathways, Toxicity Endpoints and Risk Estimation Approach .. 60 Table 3-3 NMP Studies with Evidence for Developmental Toxicity .. 62 Table 3-4 Summary of Derivation of the PODs for Fetal Resorptions and Fetal Mortality Following Acute Exposure to NMP .. 75 Table 3-5 Summary of Derivation of the PODs for Decreased Body Weight Following Chronic Exposure to NMP.

9 77 Table 4-1 Margin of Exposure (MOE) Equation to Estimate Non-Cancer risks Following Acute or Chronic Exposures to NMP .. 80 Table 4-2 Use Scenarios, Populations of Interest and Toxicological Endpoints for Assessing risks to NMP-containing Paint Strippers .. 81 Table 4-3 Acute Risk Estimates for Occupational Exposures to NMP-Based Paint Strippers - Miscellaneous Stripping Activities .. 84 Table 4-4 Acute Risk Estimates for Occupational Exposures to NMP-Based Paint Strippers Graffiti Removal .. 85 Table 4-5 Acute Risk Estimates for Consumer Exposures to NMP-Based Paint Strippers .. 88 Table 4-6 Chronic Risk Estimates for Occupational Exposures to NMP-Based Paint Strippers - Miscellaneous Stripping Activities .. 91 Table 4-7 Chronic Risk Estimates for Occupational Exposures to NMP-Based Paint Strippers Graffiti Removal .. 92 Table 4-8 Spectrum of Exposure and risks Based on Scenarios Evaluated in This Risk 105 LIST OF APPENDIX TABLES Table_Apx A-1 Aquatic Toxicity Data for NMP - Acute Toxicity.

10 122 Table_Apx A-2 Aquatic Toxicity Data for NMP - Chronic Toxicity .. 123 Table_Apx A-3 Aquatic Toxicity Data for NMP - Wildlife .. 124 Table_Apx B-1 National Chemical Information for NMP from 2012 CDR .. 125 Table_Apx B-2 Summary of Industrial NMP Uses from 2012 CDR .. 125 Table_Apx B-3 NMP Commercial/Consumer Use Category Summary .. 127 Table_Apx B-4 Consumer Uses of NMP .. 128 Table_Apx C-1 State NMP Regulations .. 129 Table_Apx D-1 Study Quality Criteria and Acceptance Specifications .. 132 Table_Apx D-2 2007 North American Industry Classification System (NAICS) Codes .. 133 Table_Apx D-3 2007 US Economic Census Data for Painting and Wall Covering and Flooring Contractors .. 140 Table_Apx D-4 2007 US Economic Census Data for Automotive Body, Paint and Interior Repair and Maintenance .. 141 Table_Apx D-5 2007 US Economic Census Data for Reupholstery and Furniture Repair .. 142 Table_Apx D-6 2007 US Economic Census Data for Industry Sectors that May Engage in Art Restoration and Conservation Activities.