TSCA Work Plan Chemical Risk Assessment - N ... - US EPA

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.

2 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 .. 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.

3 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 .. 68 Identification of Studies for BMD Modeling .. 68 Derivation of Internal Doses .. 69 PODs for Acute Exposure.

4 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.

5 99 Key Uncertainties in the Risk Assessment .. 101 RISK Assessment CONCLUSIONS .. 103 REFERENCES .. 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.

6 130 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 .. 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.

7 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 .. 197 E-5-6 NMP Scenario 6a. Coffee Table, Spray-On, Workshop, User in workshop during wait time, ACH, Weight Fraction.

8 200 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.

9 221 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 .. 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.

10 240 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 .. 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.