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&EPA
EPA Document# EPA-740-R1--8009
October 2019, DRAFT
United States Office of Chemical Safety and
Environmental Protection Agency Pollution Prevention
Methyl-)
(NMP)
Draft Risk Evaluation
N-Methylpyrrolid
(2-Pyrrolidinone, 1-
CASRN:
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TABLE OF CONTENTS
ACKNOWLEDGEMENTS 14
ABBREVIATIONS 15
EXECUTIVE SUMMARY 17
1 INTRODUCTION 25
1.1 Physical and Chemical Properties 27
1.2 Uses and Production Volume 28
1.2.1 Data and Information Sources 28
1.2.2 Toxics Release Inventory Data 29
1.3 Regulatory and Assessment History 31
1.4 Scope of the Evaluation 32
1.4.1 Conditions of Use Included in the Draft Risk Evaluation 32
1.4.2 Conceptual Model 41
1.5 Systematic Review 46
1.5.1 Data and Information Collection 46
1.5.2 Data Evaluation 53
1.5.3 Data Integration 53
2 EXPOSURES 54
2.1 Fate and Transport 55
2.1.1 Fate and Transport Approach and Methodology . 55
2.2 Releases to the Environment 58
2.3 Environmental Exposures . 58
2.3.1 Presence in the Environment and Biota 58
2.3.2 Aquatic En\imnmental Exposures 59
2.4 Human Exposures 59
2.4.1 Occupational Exposures 66
2.4 I I Occupational Exposures Approach and Methodology 66
24 12 Occupational Exposure Scenarios 71
2 4.1.2.1 Manufacturing 73
2 4 1.2.2 Repackaging 77
2 4 12 3 Chemical Processing, Excluding Formulation 79
2 4 12 4 Incorporation into Formulation, Mixture, or Reaction Product 82
2.4 I 2 5 Metal Finishing 86
2.4.1.2 (•> Removal of Paints, Coatings, Adhesives and Sealants 91
2.4.1.2.7 Application of Paints, Coatings, Adhesives and Sealants 94
2.4.1.2.8 Electronic Parts Manufacturing 100
2.4.1.2.9 Printing and Writing 105
2.4.1.2.10 Soldering 108
2.4.1.2.11 Commercial Automotive Servicing 110
2.4.1.2.12 Laboratory Use 114
2.4.1.2.13 Cleaning 117
2.4.1.2.14 Fertilizer Application 121
2.4.1.2.15 Wood Preservatives 124
2.4.1.2.16 Recycling and Disposal 127
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2.4.1.3 Summary of Occupational Exposure Assessment 130
2.4.1.4 Summary of Uncertainties for Occupational Exposure Parameters 136
2.4.2 Consumer Exposures 139
2.4.2.1 Consumer Exposures Approach and Methodology 139
2.4.2.2 Exposure Routes 141
2.4.2.3 Overview of Models used in Consumer Exposure Estimates 143
2.4.2.4 Consumer Model Scenario and Input Parameters for Exposure to Specific NMP Uses
143
2.4.2.5 Consumer Exposure Scenarios 147
2.4.2.6 Key Assumptions and Confidence 159
2.5 Other Exposure Considerations 163
2.5.1 Potentially Exposed or Susceptible Subpopulations 163
2.5.2 Aggregate and Sentinel Exposures 163
3 HAZARDS 164
3.1 Environmental Hazards 164
3.1.1 Approach and Methodol ogy 164
3.1.2 Hazard Identification 164
3.1.2.1 Toxicity Data for Aquatic Organisms 164
3.1.2.2 Concentrations of Concern Calculation... 166
3.1.2.3 Toxicity to Soil/Sediment and Terrestrial Organisms . 167
3.1.3 Weight of Scientific Evidence 167
3.1.4 Summary of Environmental Hazard 168
3.2 Human Health Hazards 168
3.2.1 Approach and Methodology 168
3.2.2 Toxicokinetics 170
3.2.3 Hazard Idem ill cation 171
3.2.3.1 Non-Cancer Hazards 171
3.2.3.2 Genotoxicily and Cancer I la/ards 177
3.2.3.2.1 Genotoxicily and Oilier Mechanistic Data 177
3 2 3.2 2 Carcinogenicity 181
3.2.4 Weight of Scientific Evidence 182
3 2 4 1 Weight of Scientific l-\ idence for Developmental Toxicity 183
3 2.4 I Weight of Scientific Evidence for Reproductive Toxicity 184
3.2.5 Dose-Response Assessment 186
3.2 5 I Selection of Endpoints for Dose-Response Assessment 189
3.2.5.2 Dose Metrics Selected 195
3.2.5.3 Potentially Exposed and Susceptible Subpopulation 198
3.2.5.4 Derivation of Candidate Values 198
3.2.5.5 Derivation of Internal Doses 199
3.2.5.6 Points of Departure for Human Health Hazard Endpoints 202
3.2.6 Summary of Human Health Hazards 207
4 RISK CHARACTERIZATION 210
4.1 Environmental Risk 210
4.1.1 Risk Estimation Approach 210
4.1.2 Assumptions and Key Uncertainties for the Environment 211
4.2 Human Health Risk 212
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4.2.1 Risk Estimation Approach 212
4.2.2 Risk Estimation for Exposures for Occupational Use of NMP 214
4.2.2.1 Manufacturing of NMP 216
4.2.2.2 Repackaging 218
4.2.2.3 Chemical Processing, Excluding Formulation 220
4.2.2.4 Incorporation into Formulation, Mixture, or Reaction Product 222
4.2.2.5 Application of Paints, Coatings, Adhesives and Sealants 224
4.2.2.6 Printing and Writing 227
4.2.2.7 Metal Finishing 230
4.2.2.8 Removal of Paints, Coatings, Adhesives and Sealants 233
4.2.2.9 Cleaning 236
4.2.2.10 Commercial Automotive Servicing 238
4.2.2.11 Laboratory Use 240
4.2.2.12 Electronic Parts Manufacturing 242
4.2.2.13 Soldering 245
4.2.2.14 Fertilizer Application 247
4.2.2.15 Wood Preservatives 249
4.2.2.16 Recycling and Disposal 251
4.2.3 Risk Estimation for Exposures to NMP for Occupational Non-Users 253
4.2.4 Risk Estimation for Acute Exposures from Consumer I se of NMP 256
4.2.4.1 Adhesives and Sealants 256
4.2.4.2 Adhesives Removers 257
4.2.4.3 Auto Interior Liquid and Spray Cleaners . 259
4.2.4.4 Cleaners/Degreasers, Engine Cleaner Deureaser and Spray Lubricant 260
4.2.4.5 Paints and Arts and Craft Paint 262
4.2.4.6 Stains, Varnishes. finishes (Coalings) 263
4.2.4.7 Paint Removers 264
4.2.4.8 Risks to Bystanders 265
4.3 Assumptions and Key Sources of I Incertainty 267
4.3.1 Assumptions and I ncertainties in Occupational Exposure Assessment 267
4.3.2 Data Uncertainties in Consumer Exposure Assessment 273
4 3 2 1 Product & Market Profile 274
4 3 2 2 Westal Survey 274
4 3 2 3 Other Parameters and Data Sources 276
4.3.3 Approach and Methodology for Uncertainties in Consumer Exposure Assessment 277
4.3 3 I Deterministic vs. Stochastic Approaches 277
4.3.3.2 Sensitise Inputs 277
4.3.4 Environmental Hazard and Exposure Assumptions Uncertainties 277
4.3.5 Human Health Hazard Assumptions and Uncertainties 277
4.3.6 Risk Characterization Assumptions and Uncertainties 279
4.4 Potentially Exposed or Susceptible Subpopulations 283
4.5 Aggregate and Sentinel Exposures 284
4.6 Risk Conclusions 285
4.6.1 Environmental Risk Conclusions 285
4.6.2 Human Health Risk Conclusions 285
5 RISK DETERMINATION 300
5.1 Unreasonable Risk 300
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5.1.1 Overview 300
5.1.2 Risks to Human Health 301
5.1.2.1 Determining Non-Cancer Risks 301
5.1.3 Determining Environmental Risk 302
5.2 Risk Determination for NMP 302
6 REFERENCES 337
APPENDICES 351
Appendix A REGULATORY HISTORY 351
A. 1 Federal Laws and Regulations 351
A.2 State Laws and Regulations 356
A.3 International Laws and Regulations. 357
Appendix B LIST OF SUPPLEMENTAL DOCUMENTS 359
Appendix C FATE AND TRANSPORT 361
Appendix D RELEASES TO THE ENVIRONMENT 370
Appendix E OCCUPATIONAL EXPOSURES 373
E. 1 Information on Gloves for Pure N MP and for Formulations containing NMP ..373
E.l.l Specifications for Gloves for Pure NMP and in Paint and Coating Removal Formulations
containing NMP 373
E. 1.2 Information on Gloves and Respi rators from Safety Data Sheets (SDS) for NMP and NMP-
containing Products 376
Appendix F CONSUMER EXPOSURES 382
F.l Overview of the E-EAST.'CEM Model ..........382
F.2 Supplemental Consumer Exposure arid Risk Estimation Technical Report for NMP in Paint and
Coating Removal .....384
Appendix G ENVIRONMENTAL HAZARDS 435
Appendix II NEMAN HEALTH HAZARDS 437
H.l Hazard and Data Evaluation Summaries ..437
Jill I la/ard and Data Evaluation Summary for Acute and Short-term Oral Exposure Studies ..437
11.1.2 I lazard and Data Evaluation Summary for Reproductive and Developmental Oral Exposure
Studies 443
H. 1.3 I la/ard and Data Evaluation Summary for Reproductive and Developmental Inhalation
Exposure Studies . 449
H. 1.4 Hazard and Data Evaluation Summary for Reproductive and Developmental Dermal
Exposure Studies 452
H. 1.5 Hazard and Data Evaluation Summary for Sub-chronic and Chronic Non-cancer Inhalation
Exposure Studies 453
H. 1.6 Hazard and Data Evaluation Summary for Sub-chronic and Chronic Non-cancer Oral
Exposure Studies 458
H. 1.7 Hazard and Data Evaluation Summary for Cancer Studies 465
Appendix I PBPK MODELING 466
I.1 Rat Model .......466
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1.2 Human Model..,,. 473
1.2.1 Corrections to Human Model Structure 473
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LIST OF TABLES
Table 1-1. Physical-Chemical Properties of NMP 27
Table 1-2. Production Volume of NMP in CDR Reporting Period (2012 to 2015) a 29
Table 1-3. Summary of NMP TRI Production-Related Waste Managed from 2015-2017 (lbs) 30
Table 1-4. Summary of NMP TRI Releases to the Environment from 2015-2017 (lbs) 30
Table 1-5. Assessment History of NMP 31
Table 1-6. Categories and Subcategories of Conditions of Use Included in the Scope of the Draft Risk
Evaluation 33
Table 2-1. Environmental Fate Characteristics of NMP 57
Table 2-2. Crosswalk of Conditions of Use to Occupational and Consumer Scenarios Assessed in the
Risk Evaluation 60
Table 2-3. Glove Protection Factors for Different Dermal Protection Strategies from ECETOC TRA v3
~ 70
Table 2-4. Estimated Numbers of Workers in the Assessed Industry Uses of NMP J 72
Table 2-5. Summary of Parameters for PBPK Modeling of Worker Inhalation Exposure I )uii rig
Manufacturing 74
Table 2-6. Summary of Parameters for Worker Dermal l-xposuiv lo Liquids During Manufacturing.... 75
Table 2-7. Characterization of PBPK Model Input Parameters lor Manufacturing of NMP 75
Table 2-8. PBPK Model Input Parameters for Manufacturing of \M P 76
Table 2-9. Characterization of PBPK Model Input Parameters lor Repackaging 77
Table 2-10. PBPK Model Input Parameters for Repackaging... 78
Table 2-11. Summary of Parameters for PBPK Modeling of Worker Inhalation Exposure During
Chemical Processing 80
Table 2-12. Summary of Parameters for Worker Dermal Exposure lo Liquids During Chemical
Processing, Excluding Formulation 80
Table 2-13. Characterization of PBPK Model Input Parameters for Chemical Processing, Excluding
Formulation 81
Table 2-14. PBPK Model Input Parameters for Chemical Processing, Excluding Formulation 81
Table 2-15. Summary of Parameters for PBPK Modeling of Worker Inhalation Exposure During
Incorporation into Formulation, Mixture or Reaction Product 83
Table 2-16 Summary of Parameters for Worker Dermal Exposure to Liquids During Incorporation into
Formulation. Mixture, or Reaction Product 84
Table 2-1 7 Characterization of PBPK Model Input Parameters for Incorporation into Formulation,
Mixture or Reaction Product 84
Table 2-1S PIJPK Model Input Parameters for Incorporation into Formulation, Mixture or Reaction
Product 85
Table 2-19. Summary of Parameters for PBPK Modeling of Worker Inhalation Exposure During Metal
Finishing 87
Table 2-20. Summary of Parameters for Worker Dermal Exposure to Liquids During Metal Finishing 88
Table 2-21. Characterization of PBPK Model Input Parameters for Metal Finishing 89
Table 2-22. PBPK Model Input Parameters for Metal Finishing 89
Table 2-23. Summary of Parameters for PBPK Modeling of Worker Inhalation Exposure During
Removal of Paints, Coatings, Adhesives and Sealants 91
Table 2-24. Summary of Parameters for PBPK Modeling of Worker Dermal Exposure to Liquids During
Removal of Paints, Coatings, Adhesives and Sealants 92
Table 2-25. Characterization of PBPK Model Input Parameters for Removal of Paints, Coatings,
Adhesives and Sealants 93
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Table 2-26. PBPK Model Input Parameters for Removal of Paints, Coatings, Adhesives and Sealants . 93
Table 2-27. Summary of Parameters for PBPK Modeling of Worker Inhalation Exposure During
Application 95
Table 2-28. Summary of Parameters for Worker Dermal Exposure to Liquids During Application of
Paints, Coatings, Adhesives and Sealants 97
Table 2-29. Characterization of PBPK Model Input Parameters for Application of Paints, Coatings,
Adhesives, and Sealants 97
Table 2-30. PBPK Model Input Parameters for Application of Paints, Coatings, Adhesives and Sealants
98
Table 2-31. Summary of Parameters for PBPK Modeling of Worker Inhalation Exposure During
Electronic Parts Manufacturing 101
Table 2-32. Summary of Parameters for Worker Dermal Exposure During Electronic Parts
Manufacturing 102
Table 2-33. Characterization of PBPK Model Input Parameters for Electronic Pails Manufacturing... 103
Table 2-34. PBPK Model Input Parameters for Electronic Parts Manufacturing 103
Table 2-35. Summary of Parameters for PBPK Modeling of Worker Inhalation l-xposure During
Printing and Writing 105
Table 2-36. Summary of Parameters for Worker Dermal l-xposure lo I .i quids During Printing and
Writing 106
Table 2-37. Characterization of PBPK Model Tnput Parameters lor Printing and Writing 106
Table 2-38. PBPK Model Input Parameters for Printing and Writing 107
Table 2-39. Summary of Parameters for Worker Dermal l .xposure During Soldering 109
Table 2-40. Characterization of PBPK Model Input Parameters for Soldering 109
Table 2-41. PBPK Model Input Parameters for Soldering . 110
Table 2-42. Summary of Parameters for PBPK Modeling of Worker Inhalation Exposure During
Commercial Automoli\c Servicing Ill
Table 2-43. Summary of Parameters for Worker Dermal Exposure to Liquids During Commercial
Automotive Servicing 112
Table 2-44. Characterization of PBPK Model Input Parameters for Commercial Automotive Servicing
112
Table 2-45. PBPK Model Input Parameters for Commercial Automotive Servicing 113
Table 2-46. Summary of Parameters for PBPK Modeling of Worker Inhalation Exposure During
Laboratory Use 114
Table 2-47. Summary of Parameters for Worker Dermal Exposure During Laboratory Use 115
Table 2-48. Characterization of PBPK Model Input Parameters by Laboratory Use 115
Table 2-49. PBPK Model Input Parameters for Laboratory Use 116
Table 2-50. Summary of Parameters for PBPK Modeling of Worker Inhalation Exposure During
Cleaning 118
Table 2-51. Summary of Parameters for Worker Dermal Exposure to Liquids During Cleaning 119
Table 2-52. Characterization of PBPK Model Input Parameters for Cleaning 119
Table 2-53. PBPK Model Input Parameters for Cleaning 120
Table 2-54. Summary of Parameters for PBPK Modeling of Worker Inhalation Exposure During
Fertilizer Application 122
Table 2-55. Summary of Parameters for Worker Dermal Exposure During Fertilizer Application 122
Table 2-56. Characterization of PBPK Model Input Parameters for Fertilizer Application 123
Table 2-57. PBPK Model Input Parameters for Fertilizer Application 123
Table 2-58. Summary of Parameters for Wood Preservatives 125
Table 2-59. Summary of Parameters for Worker Dermal Exposure to Wood Preservatives 125
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Table 2-60. Characterization of PBPK Model Input Parameters for Wood Preservatives 126
Table 2-61. PBPK Model Input Parameters for Wood Preservatives 126
Table 2-62. Summary of Parameters for PBPK Modeling of Worker Inhalation Exposure During
Recycling and Disposal 128
Table 2-63. Summary of Parameters for Worker Dermal Exposure During Recycling and Disposal... 129
Table 2-64. Characterization of PBPK Model Input Parameters for Recycle and Disposal 129
Table 2-65. PBPK Model Input Parameters for Recycle and Disposal 129
Table 2-66. Parameter Inputs to PBPK for Central and High-End Scenarios by Use 131
Table 2-67. PBPK Exposure Results for Central and High-End Worker and ONIJ Scenarios by Use.. 134
Table 2-68. Conditions of Use for Consumer Products Containing NMP . 140
Table 2-69. Consumer Exposures Assessment Literature Sources 141
Table 2-70. NMP Oral Exposure to Children via Mouthing 142
Table 2-71. Product Use Input Parameters for CEM Modeling 143
Table 2-72. Consumer Conditions of Use and Modeling Tnput Parameters 145
Table 2-73. Estimated21 NMP Air Concentrations (Time A\ eraged Over 1 Day) Based on Residential
Use of Adhesives or Sealants 148
Table 2-74. Estimated NMP Exposures (Time Averaged ()\ er I Day) Based on Residential Use of
Adhesives or Sealants 149
Table 2-75. Estimated21 NMP Air Concentrations (Time A\ eraued ()\ er 1 Day) Based on Residential
Use of Adhesives Removers 149
Table 2-76. Estimated NMP Exposures (Time Averaged Over 1 Day) Based on Residential Use of
Adhesive Removers 150
Table 2-77. Estimated11 NMP Air Concentrations (Time A\ eraued Over 1 Day) Based on Residential
Use of Auto Interior Liquid or Spray Cleaners 151
Table 2-78. Estimated NMP Exposures (Time Averaged On er I Day) Based on Residential Use of Auto
Interior Liquid or Spray Cleaners 152
Table 2-79. Estimated11 NMP Air Concentrations (Time Averaged Over 1 Day) Based on Residential
Use of Cleaners/Degreasers, Engine Cleaner/Degreaser and Spray Lubricant 153
Table 2-80. Estimated NMP Exposures (Time Averaged Over 1 Day) Based on Residential Use of
Cleaners'Degreasers, Engine Cleaner/Degreaser and Spray Lubricant 154
Table 2-SI l-slimaled'1 NMP Air Concentrations (Time Averaged Over 1 Day) Based on Residential
I se of Paint and Ails and Crafts Paint 154
Table 2-S2 Estimated NMP INposures (Time Averaged Over 1 Day) Based on Residential Use of
Paints and Ails and Crafts Paints 156
Table 2-S3 l-siiniateda NMP Air Concentrations (Time Averaged Over 1 Day) Based on Residential
I se of Stains, Varnishes, Finishes (Coatings) 156
Table 2-84. Estimated NMP Exposures (Time Averaged Over 1 Day) Based on Residential Use of
Stains. Varnishes, Finishes (Coatings) 157
Table 2-85. Estimated NMP Air Concentrations (Time Averaged Over 1 Day) Based on Residential Use
Paint Removers 158
Table 2-86. Estimated NMP Exposures (Time Averaged Over 1 Day) Based on Residential Use of Paint
Removers 158
Table 2-87. Estimated Bystander Exposure to NMP Consumer Use 159
Table 3-1. Aquatic Toxicity Data for NMP 166
Table 3-2. Acceptable Studies Evaluated for Developmental Effects 174
Table 3-3. Acceptable Studies Evaluated for Reproductive Effects 175
Table 3-4. Summary of In Vivo Genotoxicity Studies 178
Table 3-5. Summary of In Vitro Genotoxicity Studies 179
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Table 3-6. Summary of Tumor Incidence Data from Cancer Bioassays 182
Table 3-7. Summary of Exposure Pathways and Toxicity Endpoints used for Risk Evaluation 186
Table 3-8. Evidence for NMP-induced Developmental Toxicity 187
Table 3-9. Evidence for NMP-induced Reproductive Toxicity 189
Table 3-10. Summary of Derivation of the PODs for Fetal Resorptions and Fetal Mortality Following
Acute Exposure to NMP 203
Table 3-11. Summary of Derivation of the PODs for Reproductive and Developmental Effects
Following Chronic Exposure to NMP 205
Table 3-12. PODs Selected for Non-Cancer Effects from NMP Exposures 207
Table 4-1. Concentrations of Concern (COCs) for Environmental Toxicity 210
Table 4-2. Calculated Risk Quotients (RQs) for NMP 210
Table 4-3. Use Scenarios, Populations of Interest and Toxicological Endpoints for Assessing
Occupational Risks Following Acute and Chronic Exposures to NMP 213
Table 4-4. Use Scenarios, Populations of Interest and Toxicological Endpoints for Assessing Consumer
Risks Following Acute Exposures to NMP 214
Table 4-5. Non-Cancer Risk Estimates for Acute Exposures Following Occupational Use of NMP in
Manufacturing a 216
Table 4-6. Non-Cancer Risk Estimates for Chronic Exposures Following Occupational Use of NMP in
Manufacturing a 216
Table 4-7. Non-Cancer Risk Estimates for Acute Exposures Following Occupational Use of NMP in
Importation and Repackaging a 218
Table 4-8. Non-Cancer Risk Estimates for Chronic Exposures Following Occupational Use of NMP in
Importation and Repackaging a 218
Table 4-9. Non-Cancer Risk Estimates for Acute Exposures Following Occupational Use of NMP in
Chemical Processing (Excluding Formulation) ¦' 220
Table 4-10. Non-Cancer Risk Estimates for Chronic Exposures 1'ollowing Occupational Use of NMP in
Chemical Processing (IncludingFormulation) a 220
Table 4-11. Non-Cancer Risk Esti mules lor Acute Exposures Following Occupational Use of NMP in
Formulations, Mixtures, or Reaction Products a 222
Table 4-12. Non-Cancer Risk Estimates for Chronic Exposures Following Occupational Use of NMP in
Formulations, Mixtures, or Reaction Products a 222
Table 4-13 \on-Cancer Risk Estimates for Acute Exposures Following Occupational Use of NMP in
Application of Paints, Coatings, Adhesives and Sealants a 224
Table 4-14. Non-Cancer Risk Estimates lor Chronic Exposures Following Occupational Use of NMP in
Application of Paints, Coatings, Adhesives and Sealants a 225
Table 4-1 5 Non-Cancer Risk Estimates for Acute Exposures Following Occupational Use of NMP in
Printing and Writing a 227
Table 4-16. Non-Cancer Risk Estimates for Chronic Exposures Following Occupational Use of NMP in
Printing and Writinga 228
Table 4-17. Non-Cancer Risk Estimates for Acute Exposures Following Occupational Use of NMP in
Metal Finishing a 230
Table 4-18. Non-Cancer Risk Estimates for Chronic Exposures Following Occupational Use of NMP in
Metal Finishing a 231
Table 4-19. Non-Cancer Risk Estimates for Acute Exposures Following Occupational Use of NMP in
the Removal of Paints, Coatings, Adhesives and Sealantsa 233
Table 4-20. Non-Cancer Risk Estimates for Chronic Exposures Following Occupational Use of NMP in
the Removal of Paints, Coatings, Adhesives and Sealants a 234
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Table 4-21. Non-Cancer Risk Estimates for Acute Exposures Following Occupational Use of NMP in
Cleaning a 236
Table 4-22. Non-Cancer Risk Estimates for Chronic Exposures Following Occupational Use of NMP in
Cleaning a 237
Table 4-23. Non-Cancer Risk Estimates for Acute Exposures Following Occupational Use of NMP in
Commercial Automotive Servicing a 238
Table 4-24. Non-Cancer Risk Estimates for Chronic Exposures Following Occupational Use of NMP in
Commercial Automotive Servicing a 239
Table 4-25. Non-Cancer Risk Estimates for Acute Exposures Following Occupational Use of NMP in
Laboratories a 240
Table 4-26. Non-Cancer Risk Estimates for Chronic Exposures Following Occupational Use of NMP in
Laboratories a 241
Table 4-27. Non-Cancer Risk Estimates for Acute Exposures Following Occupational Use of NMP in
Electronic Parts Manufacturing a 242
Table 4-28. Non-Cancer Risk Estimates for Chronic Exposures Following Occupational Use of NMP in
Electronic Parts Manufacturing a 244
Table 4-29. Non-Cancer Risk Estimates for Acute Exposures I'oil owing Occupational I se of NMP in
Soldering a 245
Table 4-30. Non-Cancer Risk Estimates for Chronic Exposures I'ol lowing Occupational Use of NMP in
Soldering a 246
Table 4-31. Non-Cancer Risk Estimates for Acute l-\posures Following Occupational Use of NMP in
Fertilizer Application a 247
Table 4-32. Non-Cancer Risk Estimates for Chronic l-\posures I-'oil owing Occupational Use of NMP in
Fertilizer Application a 248
Table 4-33. Non-Cancer Risk Estimates for Acute Exposures I ;ol lowing Occupational Use of NMP in
Wood Preservatives ¦' 249
Table 4-34. Non-Cancer Risk Estimates lor Chronic Exposures Following Occupational Use of NMP in
Wood Preservatives ¦' 250
Table 4-35. Non-Cancer Risk Estimates lor Acute Exposures Following Occupational Recycling and
Disposal of NMP a 251
Table 4-36. Non-Cancer Risk I-stiunites for Chronic Exposures Following Occupational Recycling and
Disposal of WIP'' 251
Table 4-37 ()\U Risk I-sti mates based on Adverse Reproductive Effects (Decreased 253
Table 4-3S \on-Cancer Risk I-sti mates for Acute Exposures Following Consumer Use of NMP in
Adhesives and Sealants 256
Table 4-31) Non-Cancer Risk Estimates for Acute Exposures Following Consumer Use of NMP in the
Remo\ al of Adhesives 257
Table 4-40. Non-Cancer Risk Estimates for Acute Exposures Following Consumer Use of NMP in Auto
Interior Liquid and Spray Cleaners 259
Table 4-41. Non-Cancer Risk Estimates for Acute Exposures Following Consumer Use of NMP in
Cleaners/Degreasers, Engine Cleaner/Degreaser and Spray Lubricant 260
Table 4-42. Non-Cancer Risk Estimates for Acute Exposures Following Consumer Use of NMP in Paint
and Arts and Craft Paint 262
Table 4-43. Non-Cancer Risk Estimates for Acute Exposures Following Consumer Use of NMP in
Stains, Varnishes, Finishes (Coatings) 263
Table 4-44. Non-Cancer Risk Estimates for Acute Exposures Following Consumer Use of NMP in Paint
Removers 264
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Table 4-45. Risk Estimates to Adult Bystanders for Acute Exposures Following Consumer Use of NMP
in Degreasing or Engine Degreasing 265
Table 4-46. Risk Estimates for Adverse Developmental Effects (Increased Resorptions/Fetal Mortality)
from Acute Exposure to Bystanders via Consumer Use of NMP in Degreasing or Engine
Degreasing 266
Table 4-47. Summary of Occupational Air Concentration Estimate Approaches 268
Table 4-48. Summary of Worker Dermal Parameter Estimate Approaches 270
Table 4-49. Comparison of NMP Exposures by Route Showing Percent Exposure Due to Dermal
Contact with Liquid from Chronic NMP Exposures a 279
Table 4-49. Summary of Risk Estimates for Aggregate Exposures to Workers by Condition of Use... 287
Table 4-50. Summary of Risk Estimates from Acute Exposures to Consumers by Conditions of Use. 297
Table 6-1. NMP Consumer Brush- and Roller-Applied Paint Removal Scenario Descriptions and
Parameters 388
Table 6-2. NMP Consumer Spray-Applied Paint Removal Scenario Descriptions and Parameters 389
Table 6-3 Risk Estimates for Additional Scenarios for Users Assuming Dermal Exposure During
Application and Scrapping 390
LIST OF FIGURES
Figure 1-1. NMP Life Cycle Diagram 40
Figure 1-2. NMP Conceptual Model for Industrial and Commercial Activities and Uses: Potential
Exposures and Hazards 42
Figure 1-3. NMP Conceptual Model for Consumer Acli\ ities and Uses: Potential Exposures and
Hazards 43
Figure 1-4. NMP Conceptual Model for Environmental Releases and Wastes: Potential Exposures and
Hazards 44
Figure 1-5. Key/Suppoi tinu Data Sources for Environmental Fate and Transport 48
Figure 1-6. Key/Suppoitinu Sources lor Releases and Occupational Exposures 49
Figure 1-7. Key/Supportinu Sources for (ieneral Population, Consumer and Environmental Exposures 50
Figure 1-8. Key/Supporting Data Sources for I ji\ ironmental Hazards 51
Figure l-1^ I .iterature I-'low Diagram for I luman I lealth Key/Supporting Data Sources 52
Figure 3-1 Summary of WIP Systematic Review 170
Figure 3-2 Studies that Measured Reproductive and Developmental Effects after Repeated Dose Oral or
Dermal Exposure .... 191
Figure 3-3. Studies that Measured Reproductive and Developmental Effects after Repeated Dose
Inhalation Exposure 192
Figure 3-4. Analysis of Fit \\ eraue Daily AUC vs Fetal or Postnatal Body Weight 197
LIST OF APPENDIX TABLES
Table_Apx A-l. Federal Laws and Regulations 351
Table_Apx A-2. State Laws and Regulations 356
Table_Apx A-3. Regulatory Actions by Other Governments and Tribes 357
Table_Apx C-l. Biodegradation Study Summary for N-Methylpyrrolidone 362
Table_Apx C-2. Photolysis Study Summary for N-Methyl-2-pyrrolidone 367
TableApx D-l. Summary of NMP TRI Releases to the Environment in 2015 (lbs) 370
Table_Apx D-2. Estimated NMP Surface Water Concentrations11 371
Table_Apx E-l. Glove Types Evaluated for Pure N-Methylpyrrolidone (NMP) 374
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TableApx E-2. Recommended Glove Materials and Respiratory Protection for NMP and NMP-
Containing Products from Safety Data Sheets 377
Table Apx G-l. On-topic aquatic toxicity studies that were evaluated for N-Methylpyrrolidone 435
Table Apx H-l. Hazard and Data Evaluation Summary for Acute and Short-term Oral Exposure Studies
437
Table Apx H-2. Hazard and Data Evaluation Summary for Reproductive and Developmental Oral
Exposure Studies 443
Table Apx H-3. Hazard and Data Evaluation Summary for Reproductive and Developmental Inhalation
Exposure Studies 449
Table Apx H-4. Hazard and Data Evaluation Summary for Reproducti\ e and Developmental Dermal
Exposure Studies 452
Table Apx H-5. Hazard and Data Evaluation Summary for Sub-chronic and Chronic Non-cancer
Inhalation Exposure Studies 453
Table Apx H-6. Hazard and Data Evaluation Summary for Sub-chronic and Chronic Non-cancer Oral
Exposure Studies 458
Table Apx H-7. Summary of Tumor Incidence Data from Animal Cancer Bioassays 465
TableApx 1-1. Estimated PBPK Parameters for Each Subject of I lie Bader and van Thriel (2006)
Experiments 481
LIST OF APPENDIX FIGURES
FigureApx 1-1. Model Fits to IV Injection Data in Rats 468
FigureApx 1-2. Model Fits to Rat Oral PK Data 469
Figure Apx 1-3. Model Fits to Dermal PK Data from Pa\ an el al (2003) in Rats 471
Figure Apx 1-4. Model Simulations vs. Inhalation PK Data from (iliantous (1995) for NMP Inhalation
in Rats 472
Figure Apx 1-5. NMP Blood Concentration Data from Bader and van Thriel (2006) 478
Figure Apx 1-6. Alternate Fits to Collective Data from Bader and van Thriel (2006) 479
FigureApx 1-7. Model Fits to Subjects I and 4 of Bader and van Thriel (2006) 482
Figure Apx 1-8. Model Fits to Subjects 1<> and 12 of Bader and van Thriel (2006) 483
FigureApx 1-9. Model Fits to Subjects 14 and lo of Bader and van Thriel (2006) 484
Figure Apx I-10. Model Fits to Subjects 17 and 25 of Bader and van Thriel (2006) 485
Figure Apx 1-11. Model Fits to Human Inhalation Data of Akesson and Paulsson (1997), With and
Without Dermal Absorption of Vapors 486
Figure Apx 1-12 Model Fits to Human Dermal Exposure Data of Akesson et al. (2004) 488
Figure Apx I-13 Workplace Observer Simulations Representing Subjects of Xioafei et al. (2000).... 488
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ACKNOWLEDGEMENTS
This report was developed by the United States Environmental Protection Agency (U.S. EPA), Office of
Chemical Safety and Pollution Prevention (OCSPP), Office of Pollution Prevention and Toxics (OPPT).
Acknowledgements
The OPPT Assessment Team gratefully acknowledges participation and/or input from Intra-agency
reviewers that included multiple offices within EPA, Inter-agency reviewers that included multiple
Federal agencies, and assistance from EPA contractors ERG (Contract Xo F.P-W-12-006), Versar
(ContractNo. EP-W-17-006), ICF (ContractNo. EPC14001) and SRC (Contract No. EP-W-12-003).
Docket
Supporting information can be found in the public docket: iz36
Disclaimer
Reference herein to any specific commercial products, process or service by trade name, trademark,
manufacturer or otherwise does not constitute or imply its endorsement, recommendation or favoring by
the United States Government.
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ABBREVIATIONS
°C Degrees Celsius
atm Atmosphere(s)
ATSDR Agency for Toxic Substances and Disease Registry
BAF Bioaccumulation Factor
BCF Bioconcentration Factor
CAA Clean Air Act
CASRN Chemical Abstracts Service Registry Number
CBI Confidential Business Information
CCL Contaminant Candidate List
CDR Chemical Data Reporting
CEM Consumer Exposure Model
CFR Code of Federal Regulations
cm3 Cubic Centimeter(s)
COC Concentration of Concern
DTSC Department of Toxic Substances Control
EC European Commission
EC50 Effective Concentration with 50% immobilized lest organisms
ECHA European Chemicals Agency
EPA Environmental Protection Agency
EPCRA Emergency Planning and CommunityRight-to-Knou Act
ESD Emission Scenario Document
EU European Union
FDA Food and Drug Administration
FFDCA Federal Food, Drug and Cosmetic Act
GBL Gam m a- B uty rol act o 11 c
GS Generic Scenarios
HESIS Hazard Evaluation System and Information Service
HHE Health Hazard l-\aluation
HPV High Production Volume
Hr I lour
IMAP Inventory Multi-Tiered Assessment and Prioritisation
IRIS Integrated Risk Information System
kg kilogram(s)
L l.iterfs)
LOAEL I ,o\\ est Observed Adverse Effect Level
LOEC Lowest Observed Effect Concentration
lb Pound(s)
LC50 Lethal Concentration to 50% of test organisms
LOEC Lowest Observed Effect Concentration
Log Koc Logarithmic Soil Organic Carbon:Water Partition Coefficient
Log Kow Logarithmic Octanol:Water Partition Coefficient
m3 Cubic Meter(s)
MADL Maximum Allowable Dose Level
mg Milligram(s)
NOAEL No Observed Adverse Effect Level
NOEC No Observed Effect Concentration
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ONU
Occupational Non-User
ng
Microgram(s)
MMA
Monomethylamine
mmHg
Millimeter(s) of Mercury
mPas
Millipascal(s)-Second
MITI
Ministry of International Trade and Industry
SDS
Safety Data Sheet
MSW
Municipal Solid Waste
NAICS
North American Industry Classification System
NESHAP
National Emission Standards for Hazardous Air Pollutants
NICNAS
National Industrial Chemicals Notification and Assessment Scheme
NIOSH
National Institute for Occupational Safety and Health
NMP
N-Methy lpy rroli done
NWQMC
National Water Quality Monitoring Council
OCSPP
Office of Chemical Safety and Pollution Prevention
OECD
Organisation for Economic Cooperation and Development
OEHHA
Office of Environmental Health Hazard Assessment
OEL
Occupational Exposure Limits
OPPT
Office of Pollution Prevention and Toxics
OSHA
Occupational Safety and Health Administration
PBZ
Personal Breathing Zone
PDE
Permissible Daily Exposure
PDM
Probabilistic Dilution Model
PECO
Populations, Exposures, Comparisons. Outcomes
PEL
Permissible Exposure Limit
PF
Protection Factor
POD
Point of Departure
POTW
Publicly Owned Treatment Works
PPE
Personal Protectee l-<.|ui|niienl
ppm
Part(s) per Million
PSD
Particle Size Distribution
RCRA
Resource Conservation and Recovery Act
REACH
Registration. l -\ aluation. Authorisation and Restriction of Chemicals
SDWA
Safe Drinking Water Act
SIDS
Screening Information Data Set
STORET
STO rage and RETrieval
SVHC
Substance of Very High Concern
TRI
Toxics Release Inventory
TSCA
Toxic Substances Control Act
TWA
Time-Weighted Average
USGS
United States Geological Survey
VOC
Volatile Organic Compound
WEEL
Workplace Environmental Exposure Level
Yr
Years
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EXECUTIVE SUMMARY
This draft risk evaluation for N-methylpyrrolidone (NMP) was performed in accordance with the Frank
R. Lautenberg Chemical Safety for the 21st Century Act and is being disseminated for public comment
and peer review. The Frank R. Lautenberg Chemical Safety for the 21st Century Act amended the Toxic
Substances Control Act (TSCA), the Nation's primary chemicals management law, in June 2016. As per
EPA's final rule. Procedures for Chemical Risk Evaluation Under the An ic Substances
Control Act (82 FR 33726). EPA is taking comment on this draft, and will also obtain peer review on
this draft risk evaluation for NMP. All conclusions, findings, and determinations in this document are
preliminary and subject to comment. The final risk evaluation may change in response to public
comments received on the draft risk evaluation and/or in response to peer review, which itself may be
informed by the public comments. The preliminary conclusions, findings, and determinations in this
draft risk evaluation are for the purpose of identifying whether the chemical substance presents
unreasonable risk or no unreasonable risk under the conditions of use, in accordance with TSCA section
6, and are not intended to represent any findings under TSC A section 7.
TSCA § 26(h) and (i) require EPA to use scientific information, technical procedures, measures,
methods, protocols, methodologies and models consistent with the best available science and to base its
decisions on the weight of the scientific evidence To meet these TSCA. § 26 science standards, EPA
used the TSCA systematic review process described in the Application of Systematic Review in TSCA
Risk Evaluations document ( X)Jj! ) The data collection, evaluation, and integration stages of
the systematic review process are used to develop the exposure, late, and hazard assessments for risk
evaluations.
N-Methylpyrrolidone (( ASKN X72-5<)-4), also called n-methyl-2-pyrrolidone, or l-methyl-2-
pyrrolidone, is a water-miscible. organic solvent that is often used as a substitute for halogenated
solvents. NMP exhibits a unique set of physical-chemical properties that have proven useful in a range
of industrial, commercial and consumer applications. NMP has low volatility and high affinity for
aromatic hydrocarbons, w liich makes it effective for solvent extraction in petrochemical processing and
pharmaceutical manufacturing NMP is also valued for its high polarity and low surface tension which
are considered optimal lor sol\ ent cleaning and surface treatment of metals, textiles, resins, and plastics.
NMP is subject to federal and state regulations and reporting requirements. NMP has been a reportable
chemical to Toxics Release Inventory (TR1) substance under Section 313 of the Emergency Planning
and Community Right-to-Know Act (EPCRA) since January 1, 1995.
NMP is widely used in the chemical manufacturing, petrochemical processing and electronics industries.
There is also growing demand for NMP use in semiconductor fabrication and lithium ion battery
manufacturing (FM s J: ) In the commercial sector, NMP is primarily used for producing and
removing paints, coatings and adhesives. Other applications include, but are not limited to, use in
solvents, reagents, sealers, inks and grouts. EPA evaluated the following categories of conditions of use
for NMP: manufacturing; processing; distribution in commerce, industrial, commercial and consumer
uses and disposal. The total aggregate production volume for NMP decreased slightly from 164 to 160
million pounds between 2012 and 2015.
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Approach
EPA used reasonably available information (defined in 40 CFR 702.33 as "information that EPA
possesses, or can reasonably generate, obtain, and synthesize for use in risk evaluations, considering the
deadlines for completing the evaluation) in a "fit-for-purpose" approach, to develop a risk evaluation
that relies on the best available science and is based on the weight of the scientific evidence. EPA used
previous analyses as a starting point for identifying key and supporting studies to inform the exposure,
fate, and hazard assessments. EPA also evaluated other studies that were published since these reviews.
EPA reviewed the information and evaluated the quality of the methods and reporting of results of the
individual studies using the evaluation strategies described in Application of Systematic Review in
TSCA Risk Evaluations ( .QlSaY
In the problem formulation document, EPA identified the NMP conditions of use and presented three
conceptual models and an analysis plan for the current draft risk evaluation. Jn this draft risk evaluation,
EPA evaluated risks to aquatic species from environmental releases to surface water associated with the
manufacturing, processing, distribution, use and disposal of NMP. EPA also evaluated the risks posed to
workers and consumers, as well as occupational non-users (i c . workers who do not directly handle
NMP but perform work in an area where it is used) and consumer bystanders (i.e., non-users who are
incidentally exposed to NMP as a result of the use of consumer products containing NMP).
Exposures
EPA evaluated acute and chronic exposures lor aquatic species as a screening level risk assessment for
ambient surface water exposures associated with NMP environmental releases from the manufacturing,
processing, distribution, use and disposal. EPA used environmental release data from EPA's Toxics
Release Inventory (TRI) to derive conservative estimates of NMP surface water concentrations (acute
and chronic) near facilities reporting the highestNMP water releases.
NMP may occur in \ arious en\ ironniental media including sediment, soil, water and air. As part of the
NMP Problem Formulation ( ). EPA completed a preliminary analysis of environmental
exposures for aqualic terrestrial species to NMP in these environmental media. No additional
information has been received or otherwise identified by EPA that would alter the conclusions presented
in the NMP Problem f ormulation ( 'A. 2018c). EPA concluded that no further analysis of
environmental release pathways for en\ ironmental receptors is necessary based on a qualitative
assessment of the physical chemistry and fate properties of NMP and the levels of NMP exposure that
may be expected for organisms that inhabit these environmental compartments.
EPA evaluated acute and chronic human exposures by the dermal and inhalation routes, including direct
contact with NMP-containinu liquids and indirect exposure from vapor-through-skin uptake. For each
occupational use scenario. I- PA considered moderate and high-end exposure parameters and the impact
of different combinations of personal protective equipment (PPE) on exposure. Empirical data were
preferred for exposure estimation when available. In the absence of measured data, EPA used models to
estimate exposure to the human receptors of interest. The models' underlying input parameters and
assumptions were based on reasonably available information regarding NMP physical and chemical
properties, NMP weight fraction in the product, and the activity patterns associated with use. Exposure
to individuals located near those using NMP-containing products (i.e., nearby non-users,) were also
estimated based on inhalation and vapor-through-skin uptake.
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EPA used two different approaches to quantify acute exposures to consumers. The first approach
incorporated assumptions based on the duration of use; whereas the second approach incorporated
assumptions regarding the specific type of project involved (e.g., paint stripping a table, chest of
drawers, or bathtub).
Hazards
EPA identified acute and chronic Concentrations of Concern (COCs) for aquatic organisms based on the
available acute and chronic hazard data for NMP. These acute and chronic COCs are compared to the
estimated surface water concentrations of NMP from the exposure assessment.
Reported outcomes in laboratory animal studies range from irritation lo decreased body weight and
adverse systemic effects (e.g., liver, kidney, spleen, thymus, testes, brain) l-IW reviewed the reasonably
available information on hazard potential and selected reproductive and develop menial toxicity
endpoints in rodents (i.e., fetal mortality and decreased fertility) as the critical effects lor dose-response
analysis and risk estimation. EPA identified fetal mortalily as the critical endpoinl for acute exposures
and reduced fertility as the critical endpoint for chronic exposures.
Other outcomes, including adverse systemic effects, may occur at higher exposure concentrations. The
risk determinations in the current document are based on adverse de\ clop mental effects observed in a
potentially exposed or susceptible subpopulation (c g., pregnant women and women of child bearing age
who may become pregnant) which are expected lo lx- protective of other outcomes and other potentially
exposed or susceptible subpopulations.
Human Populations Considered in This Risk Evaluation
EPA assumed those who use NMP-containing products would be adults of either sex (>16 years old),
including pregnant women, and e\ aluatcd risks to individuals who do not use NMP but may be
indirectly exposed due to their proximity to the user who is directly handling NMP or the product
containing NMP.
The risk evaluation is hascd on potential effects on fertility as well as developmental toxicity. The
lifestages of greatest concern for dc\ clopmental effects are pregnant women and women of childbearing
age who may become pregnant Lifestages of concern for effects on reproductive health and fertility
include men and women of reproductive age as well as children and adolescents. The risk evaluation is
intended to he protective of other potentially exposed or susceptible subpopulations, including people
with pre-existing conditions and people with genetic variations that make them more susceptible.
Exposures that do not present risks based on sensitive reproductive and developmental endpoints are not
expected to present risks for other potential health effects of NMP because other health effects occur at
higher levels of exposure
Risk Characterization
This draft risk evaluation characterizes the environmental and human health risks from NMP under the
conditions of use, including manufacture, processing, distribution, use, and disposal.
Environmental Risks: For environmental risk, EPA utilized a risk quotient (RQ) to compare the
estimated acute and chronic NMP exposure concentrations in surface water to respective acute and
chronic COCs to characterize the risk to aquatic organisms. A screening level risk analysis for NMP in
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surface water and aquatic receptors resulted in RQs for the acute and chronic risk of 0.0022 and 0.85,
respectively (Table 4-2). An RQ that does not exceed 1 indicates that the exposure concentrations of
NMP are less than the concentrations expected to produce an adverse effect. Because the RQ values do
not exceed 1, and because EPA used a conservative screening level approach, these values indicate that
the risks of NMP to the aquatic organisms are unlikely. NMP is not likely to accumulate in sediment
based on its physical chemical properties and is not expected to adsorb to sediment due to its water
solubility and low partitioning to organic matter. Because NMP toxicity to sediment-dwelling
organisms is expected to be comparable to that of aquatic organisms, minimal risks are anticipated for
sediment-dwelling organisms. NMP exhibits low volatility and readily biodegrades under aerobic
conditions; therefore, the concentrations in ambient air are unlikely to reach levels that would present
risks for terrestrial organisms. Details of these estimates are in section 4.1.2.
Human Health Risks: For human health risks to workers and consumers, I -PA identified non-cancer
human health risks. Based on the exposure scenarios evaluated, risks may be anticipated for individuals
who are not directly exposed to liquid NMP (e.g., occupational non-user, consumer bystander) as a
result of indirect exposure via inhalation and vapor through skin exposures. Generally, risks identified
for workers are linked to chronic exposures, whereas risks for consumers are linked to acute exposures.
Although glove use may be effective in reducing NMP exposure, some glove types do not provide
adequate protection. Further discussion and examples of appropriate glove use are included in Appendix
E.
Strengths, Limitations and Uncertainties in the Risk ('Ihiracierization
The exposure estimates EPA used to evaluate human health risks were based on a large amount of
monitoring data and were supported by modeling data for many conditions of use. PBPK models
allowed EPA to evaluate risks from aggregate exposures from simultaneous dermal and inhalation
exposures. Robust evidence of a continuum of adverse reproductive and developmental effects support
the hazard endpoints EPA used as the basis for evaluating risks from acute and chronic exposures. In
addition, PBPK modeling reduces uncertainties around the relevance of animal data for human health.
Uncertainties around the representativeness of exposure monitoring data, activity pattern information,
PPE use and efficacy, and incomplete information on some hazard endpoints and factors that may
contribute to increased exposure and susceptibility to NMP contribute to the overall uncertainties of the
risk estimates. Overall, EPA has medium to high confidence in the risk estimates presented in this risk
characterization.
Potentially Imposed and Susceptible Subpopulations (PESS)
TSCA § 6(b)(4) requires that EPA conduct a risk evaluation of PESS. In developing the risk evaluation,
EPA analyzed the reasonably available information to ascertain whether some human receptor groups
may have greater exposure or greater susceptibility than the general population to the hazard posed by a
chemical. For consideration of the most highly exposed groups, EPA assessed NMP exposures to PESS
of interest: males, pregnant women, and women of childbearing age who may become pregnant.
Aggregate and Sentinel Exposures
EPA evaluated aggregate risks from dermal and inhalation routes of exposure for each COU. Peer-
reviewed PBPK modeling allowed EPA to integrate aggregate exposures across routes by translating
exposure concentrations into internal doses (human blood concentrations). While this assessment
evaluated specific COUs based on exposure estimates that incorporate multiple routes of exposure, it did
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not consider the potential for aggregate exposures from multiple conditions of use. EPA considered
sentinel exposure in the form of high-end estimates for consumer and occupational exposure scenarios
which incorporate dermal and inhalation exposure, as these routes are expected to present the highest
exposure potential.
Risk Determination
In each risk evaluation under TSCA section 6(b), EPA determines whether a chemical substance
presents an unreasonable risk of injury to health or the environment, under the conditions of use. These
determinations do not consider costs or other non-risk factors. In making these determinations, EPA
considers relevant risk-related factors, including, but not limited to: the effects of the chemical substance
on health and human exposure to such substance under the conditions of use (including cancer and non-
cancer risks); the effects of the chemical substance on the environment and en\ ironmental exposure
under the conditions of use; the population exposed (including any potentially exposed or susceptible
subpopulations (PESS)); the severity of hazard (including the nature of the hazard, the irreversibility of
the hazard); and uncertainties. EPA also takes into consideration the Agency's confidence in the data
used in the risk estimate. This includes an evaluation of the strengths, limitations and uncertainties
associated with the information used to inform the risk estimate and the risk characterization. The
rationale for the risk determination is discussed in section 5.
Environmental Unreasonable Risks: For all conditions of use, EPA did not identify any scenarios
indicating unreasonable risk for aquatic, sedimcni-dwelling, or terrestrial organisms from exposures to
NMP. NMP readily degrades under aerobic conditions and is not expected to persist in the environment.
Because the RQ values do not exceed 1, and because EPA used a conservative screening level approach,
these values indicate that the risks of NMP to the aquatic organisms are unlikely. As a result, EPA does
not find unreasonable risk to the en\ ironment for anv of the conditions of use for NMP (see section
4.1.2).
Unreasonable Risk to the ( ienei al Ponulation: EPA is not including general population exposures in the
risk evaluation for NMP. As explained in the Problem Formulation for the Risk Evaluation for NMP,
general population exposures were determined to he outside the scope of the risk evaluation. EPA has
determined that the existing regulatory programs and associated analytical processes adequately assess
and effectively manage the risks of NMP that may be present in various media pathways (e.g. air, water,
land) for the general population. For these cases, EPA believes that the TSCA risk evaluation should not
focus on those exposure pathways, but rather on exposure pathways associated with TSCA conditions of
use that are not subject to those regulatory processes, because the latter pathways are likely to represent
the greatest areas of concern to EPA.
Unreasonable Risk to Workers: EPA evaluated workers' acute and chronic inhalation and dermal
exposures (including uptake of vapor through skin) for non-cancer risks and determined whether any
risks indicated are unreasonable risk. The drivers for EPA's determination of unreasonable risk for
workers are reproductive effects from chronic inhalation and dermal exposures; generally, risks
identified for workers are linked to chronic exposures. The determinations reflect the severity of the
effects associated with occupational exposures to NMP and incorporate consideration of expected
personal protective equipment (PPE) (frequently estimated to be gloves with a protection factor of 5, 10,
or 20). For workers, EPA determined that the conditions of use that presented unreasonable risks
included processing of NMP into formulations or mixtures, and many industrial or commercial uses as a
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solvent or degreaser. A full description of EPA's determination for each condition of use is in section
5.2.
Unreasonable Risk to Occupational Non-Users (ONUs): EPA's exposure assessment includes estimates
of NMP exposures to occupational non-users (ONUs). ONUs are located in the general vicinity near
workers but are further from emissions sources. Unlike workers, ONUs do not have direct dermal
contact with liquids. The estimates assume ONUs are not wearing respirators. While the difference
between ONU exposures and workers directly handling the chemical generally cannot be quantified,
EPA assumes that, in most cases, ONU inhalation exposures are expected to be lower than inhalation
exposures for workers directly handling the chemical substance. To account for those instances where
monitoring data or modeling did not distinguish between worker and OM inhalation exposure
estimates, EPA considered the central tendency risk estimate when determining ONU risk. For several
conditions of use, there were risks for ONUs for high-end chronic exposures. I lo\\e\ er. risk estimates
for ONUs for the central tendency scenarios did not indicate risk. EPA determined that the conditions of
use assessed did not present an unreasonable risk for 0\l s
Unreasonable Risk to Consumers: EPA evaluated consumer acute inhalation, dermal, and vapor through
skin exposures for non-cancer risks and determined whether the risks indicated are unreasonable. Risks
for consumers were evaluated using acute exposure scenarios.J'he driver for EPA's determination of
unreasonable risk is developmental adverse effects from acute inhalation and dermal exposure. These
adverse effects include fetal mortality. EPA determined that several consumer conditions of use present
unreasonable risk of injury to health. A full description of F.PA's determination for each condition of use
is in section 5.2.
Unreasonable Risk to Bystanders (from consumer uses): EPA's exposure assessment includes estimates
of NMP exposures to bystanders (i e those located in the house during consumer product use) who do
not have direct contact with NMP-containing consumer products. EPA did not find unreasonable risk to
bystanders for the conditions of use assessed
Summary »!'Risk Determinations
EPA has determined that the following conditions of use of NMP do not present an unreasonable risk of
injury to health The details of these determinations are in tahle 5-1 in section 5 2
Conditions of I so llisil Do Not Present ;in Inrensonnhle Kisk
•
Domestic manufacture
•
Import (including repackaging and loading/unloading)
•
Processing as a reactant or intermediate in several manufacturing processes, including plastic
material and resin manufacturing and in pharmaceutical and medicine manufacturing
•
Processing as a reactant or intermediate, other
•
Processing for incorporation into articles in other sectors, including in plastic product
manufacturing
•
Repackaging for wholesale and retail trade
•
Processing - Recycling
•
Distribution in commerce
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Conditions of I so tlisit Do Not Present ;i 11 Inrensonnhle Kisk
• Industrial and commercial use in ink, toner, and colorant products, including printer ink and
inks in writing equipment
• Industrial and commercial use in processing aids, specific to petroleum production in
petrochemical manufacturing, and other uses in oil and gas drilling and pharmaceutical and
medicine manufacturing
• Industrial and commercial use in other uses in soldering materials
• Industrial and commercial use, Other Uses, Fertilizer and ( MIkt auricultural chemical
manufacturing - processing aids and solvents
• Industrial and commercial use in other uses, wood preservatix es
• Consumer use in paints and coatings, adhesive removers
• Consumer use in paints and coatings, lacquers, stains, varnishes, primers and floor finishes
• Consumer use in paint additives and coating additives not described In oilier codes, paints and
arts and crafts paints
• Consumer use in adhesives and sealants single component glues and adhesh es, including
lubricant adhesives and two-component glues and adhesi\ es including some resins
• Consumer use in other uses in automotive care products
• Consumer use in other uses lubricant and lubricant addili\ es. i ncluding hydrophilic coatings
• Disposal including industrial pre-trealmenl. industrial wastewater treatment publicly owned
treatment works (POTW), underground injection, landfill (municipal, hazardous or other land
disposal), emissions to air, incinerators (municipal and hazardous waste).
261
262 EPA determined thai the lb I lowing conditions of use of NMP present an unreasonable risk of injury to
263 health to workers or to consumers The details of these determinations are discussed in table 5-1 in
264 section 5.2.
265
Processing I ses (lint Present :in I nresisonsihle Kisk
• Incorporation into a formulation, mixture or reaction product in several industrial sectors
• Incorporation into articles as lubricants and lubricant additives in machinery manufacturing
• Incorporation into articles as paint additives and coating additives not described by other codes
in transportation equipment manufacturing
• Incorporation into articles as a solvent (which becomes part of product formulation or mixture),
including in textiles, apparel and leather manufacturing
266
Indiislri:il sinri ( oniincrehil I ses thill Present nil I nresisonsihle Kisk
• For paint and coating removers and in adhesive removers
• For paint and coatings (lacquers, stains, varnishes, primers and floor finishes, and powder
coatings, surface preparation), in paint additives and coating additives not described by other
codes in several manufacturing sectors, and in adhesives and sealants, several types
• As a solvent (for cleaning or degreasing) use in electrical equipment, appliance and component
manufacturing and for other uses in manufacturing lithium ion batteries
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Iiidnslri:il sinri (oinnieroiiil I ses llinl Present sin Inrensonnble Kisk
• As other uses in anti-freeze and de-icing products, automotive care products and lubricants and
greases
• As other uses in metal products not covered elsewhere, and lubricant and lubricant additives
including hydrophilic coatings
• As other uses in laboratory chemicals
• As other uses, cleaning and furniture care products, including wood cleaners and gasket
removers
267
C onsumer I ses llisil Present ;i 11 I nresisonsihle Kisk
• For paints and coatings, paint and coating remo\ as
• As other uses, cleaning and furniture care products, including wood cleaners and gasket
removers.
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1 INTRODUCTION
This document presents the draft risk evaluation for NMP under the Frank R. Lautenberg Chemical
Safety for the 21st Century Act. The Frank R. Lautenberg Chemical Safety for the 21st Century Act
amended the Toxic Substances Control Act, the Nation's primary chemicals management law, in June
2016.
The Agency published the Scope of the Risk Evaluation for NMP (U.S. EPA I) in June 2017, and
the problem formulation in June, 2018 (\_ r. H5 \ 2018c), which represented the analytical phase of risk
evaluation whereby "the purpose for the assessment is articulated, the problem is defined, and a plan for
analyzing and characterizing risk is determined," as described in Section 2.2 of the Framework for
Human Health Risk Assessment to Inform Decision Making. EPA received comments on the published
problem formulation for NMP and has considered the comments specific to N\IP. as well as more
general comments regarding EPA's chemical risk evaluation approach for de\ doping the draft risk
evaluations for the first 10 TSCA Workplan chemicals.
During problem formulation, EPA identified the NMP conditions of use and presented the associated
conceptual models and an analysis plan. In this risk evaluation. EPA evaluated risks to workers from
inhalation and dermal exposures by comparing the exposure estimates for acute and chronic scenarios to
the related human health hazards. While NMP is present in various en\ ironmental media such as
groundwater, surface water, and air, EPA determined during problem formulation that no further
analysis of the environmental release pathways associated with ecological exposures via ambient water,
sediments, and land-applied biosolids was needed based on a qualitati\ e assessment of the physical-
chemical properties and fate of NMP in the environment and a quantitative comparison of the hazards
and exposures identified for aquatic organisms. Risk determinations were not made as part of problem
formulation; therefore, the results from these analyses are used to inform the risk determination section
of this draft risk evaluation.
EPA used reasonably a\ ailable information consistent with the best available science for physical-
chemical and fate properties, potential exposures, and relevant hazards according to the systematic
review process I or the human exposure pathways, EPA evaluated inhalation exposures to vapors and
mists for workers and occupational non-users, and dermal exposures via skin contact with liquids and
vapor through skin uptake for workers and consumers. EPA characterized risks to ecological receptors
from exposures \ ia surface water, sediment, and land-applied biosolids in the risk characterization
section of this draft risk evaluation based on the analyses presented in the problem formulation.
This document is structured such that the Introduction (Section 1) presents the basic physical-chemical
properties of NMP, and background information on its regulatory history, conditions of use and
conceptual models, with emphasis on any changes since the publication of the problem formulation.
This section also includes a discussion of the systematic review process utilized in this draft risk
evaluation. Exposures (Section 2) provides a discussion and analysis of the exposures, both human and
environmental, that can be expected based on the conditions of use identified for NMP. Hazards
(Section 3), discusses the environmental and human health hazards of NMP. The Risk Characterization
(Section 4), integrates the reasonably available information on human health and environmental hazards
and exposures, as required by TSCA (15 U.S.C 2605(b)(4)(F)). This section also includes a discussion
of the uncertainties that underly the assessment and how they impact the risk evaluation. As required
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under TSCA 15 U.S.C. 2605(b)(4), a determination of whether the risk posed by this chemical substance
is unreasonable is presented in the Risk Determination (Section 5).
As per EPA's final rule, Procedures for Chemical Risk Evaluation Under the Amended Toxic
Substances Control Act (82 FR 33726) (hereinafter "Risk Evaluation Rule"), this draft risk evaluation is
subject to both public comment and peer review, which are distinct but related processes. EPA is
providing 60 days for public comment, which will inform the EPA Science Advisory Committee on
Chemicals (SACC) peer review process. EPA seeks public comment on all aspects of this draft risk
evaluation, including all conclusions, findings, and determinations. This is also an opportunity for EPA
to receive additional information that might be relevant to the science underlying the draft risk
evaluation and the outcome of the systematic review approach used for Wll' This review satisfies
TSCA [15 U.S.C 2605(b)(4)(H)], which requires EPA to provide public notice and ail opportunity for
comment on a draft risk evaluation prior to publishing a final risk evaluation
Peer review will be conducted in accordance with EP \\ icuulatory procedures for chemical risk
evaluations, including using the EPA Peer Revit c and other methods consistent with section
26 of TSCA (See 40 CFR § 702.45). As explained in the Risk Evaluation Rule, the purpose of the peer
review is for the independent review of the science underlying (lie risk evaluation. Peer review will
therefore address aspects of the underlying science as outlined in the charge to the peer review panel
such as hazard assessment, assessment of dose-response, exposure assessment, and risk characterization.
Peer-review supports scientific rigor and enhances transparency in the risk evaluation process.
As explained in the Risk Evaluation Rule, it is important lor peer reviewers to consider how the
underlying risk evaluation analyses fit together to produce an integrated risk characterization, which will
form the basis of an unreasonable risk determination. EPA hclic\ es peer reviewers will be most effective
in this role if they receive the benefit of public comments on draft risk evaluations prior to peer
review. For this reason, EPA is pro\ iding the opportunity for public comment before peer review on this
draft risk evaluation. The final risk e\ aluation may change in response to public comments received on
the draft risk evaluation and/or in response to peer review, which itself may be informed by public
comments. EPA will respond to public and peer re\ iew comments received on the draft risk evaluation
when it issues the final risk e\ aluation
EPA solicited input on the lust 10 chemicals, includingNMP, as it developed use dossiers, scope
documents, and problem formulations. At each step, EPA received information and comments specific
to individual chemicals and of a more general nature relating to various aspects of the risk evaluation
process, technical issues, and the regulatory and statutory requirements. EPA has considered comments
and information recei\ ed at each step in the process and factored in the information and comments as
the Agency deemed appropriate and relevant including comments on the published problem formulation
of NMP. Thus, in addition to any new comments on the draft risk evaluation, the public should re-
submit or clearly identify at this point any previously filed comments, modified as appropriate, that are
relevant to this risk evaluation and that the submitter believes have not been addressed. EPA does not
intend to further respond to comments submitted prior to the publication of this draft risk evaluation
unless they are clearly identified in comments on this draft risk evaluation.
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1.1 Physical and Chemical Properties
Physical-chemical properties influence the environmental behavior and the toxic properties of a
chemical, thereby informing the potential conditions of use, exposure pathways, routes and hazards that
EPA intends to consider. During problem formulation, EPA considered the measured or estimated
physical-chemical properties set forth in Table 1-1. Based on EPA's review of the available literature,
the vapor pressure previously reported for NMP was updated (0.345 mmHg) to conform with EPA's
data quality criteria. This value is considered more reliable than the original value (0.19 mmHg) which
was taken from a secondary source.
NMP is a high boiling, polar aprotic solvent with low viscosity and low \ olatility. It is miscible with
water and most organic solvents and exhibits low flammability and no cxplosi vity. It is not readily
oxidizable; variations in temperature and humidity can produce a range of saturation concentrations in
ambient air (U.S. EPA. 2019a. 20J7d).
Table 1-1. Physical-Chemical Properties of NMP
Properly
Value"
Reference
Molecular formula
C5H9ON
Molecular weight
99.1 g/mole
O'Neil et al. (2006)
Physical form
Colorless liquid
O'Neil et al. (2006)
Melting point
-25 C
Ashf
Boiling point
2i)2 C
O'Neil et al. (2006)
Density
1.03 at 25"C
O'Neil et al. (2006)
Vapor pressure
0.345 mmHg at 25°C
Daubert and Danner (1989)
Vapor density
3.4 (air = 1)
NFPA. (1997)
Water solubility
1 .<)')<) ii L at 25°C (miscible)
O'Neil et al. (2006)
Octanol.water partition coefficient (log kow)
-0.38 at 25°C
Sasaki et al. (1988)
Henry's I.aw constant
3.2 x 10"9 atm m3/mole
Kim et al. (2000)
Flash point
95°C (open cup)
Riddick et a 5)
Auto flammability
Not available
Viscosity
1.65 rnPa-s at 25°C
O'Neil et al. (2006)
Refractive index
Not applicable
Dielectric constant
Not applicable
a Measured unless otherwise noted.
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1.2 Uses and Production Volume
1.2.1 Data and Information Sources
The summary of use and production volume information presented below is based on research
conducted for the Problem Formulation Document for N-Methylpyrrolidone (NMP) (U.S. EPA. 2018c)
and any additional information obtained since the publication of that document. The previous research
was based on reasonably available information, including the Use and Market Profile for NMP, (EPA-
HQ-OPPT-2 ); public meetings and meetings with companies, industry groups, chemical users
and other stakeholders to aid in identifying and verifying the conditions of use included in this risk
evaluation.
NMP is an effective solvent that is widely used in the manufacture and production of electronics,
petroleum products, pharmaceuticals, polymers and other specialty chemicals ll has numerous
industrial, commercial, and consumer applications. Some of the major areas of use identified for NMP
are listed below (Barrens et at.. 2011; Ash and Ash. 20( )
1. Petrochemical processing: acetylene recovery from cracked gas, extraction of aromatics and
butadiene, gas purification (removal of CO2 and H2S). In he oil extraction
2. Engineering plastics: reaction medium for production of high-temperature polymers such as
polyether sulfones, polyamideimides and polyaramids
3. Coatings: solvent for acrylic and epoxy resins. polyurethane paints, waterborne paints or
finishes, printing inks, synthesis/diluent of wire enamels, coalescing agent
4. Specialty chemicals: solvent and/or co-solvenl for liquid formulations
5. Electronics: cleaning agent for silicon wafers, photoresist stripper, auxiliary in printed circuit
board technology
6. Industrial and domestic cleaning: component in paint strippers and degreasers
In addition to the uses in industrial, commercial, and consumer settings, NMP is used in ways
considered as mission critical to led em I agencies
The Chemical Data Reporting (CDR) Rule under TSCA (40 CFRPart 711) requires that U.S.
manufacturers and importers provide N\\ with information on chemicals they manufacture (including
imports) I or the 2016 CDR cycle, data collected for each chemical include the company name, volume
of each chemical manufactured/imported, the number of workers employed at each site, and information
on whether the chemical is used in the commercial, industrial, and/or consumer sector. Only those
companies that manufactured or imported at least 25,000 pounds of NMP per site were required to
report under the CDR rule during the 2015 calendar year (l_ A i ' ^. -SlUs)- The 2016 CDR reporting
data for NMP are pro\ ided in Table 1-2.
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Table 1-2. Production Volume of NMP in CDR Reporting Period (2012 to 2015) a
Reporting Year
2012
2013
2014
2015
Total Aggregate Production
Volume (lbs)
164,311,844
168,187,596
171,095,221
160,818,058
" The CDR data for the 2016 rcDortinu period is available via ChemView dittos://cherm oa.eov/chemviewN) (U.S. EPA.
2017c). Because of an ongoing CBI substantiation process required by amended TS(' V I lie CDR data available in the risk
evaluation document is more specific than currently in ChemView.
NMP is widely used in the chemical manufacturing, petrochemical processing and electronics industries
(FMI. 2015). In the commercial sector, it is primarily used for producing and remo\ ing paints, coatings
and adhesives. Other commercial applications include, but are not limited to, use in sol\ ents, reagents,
sealers, inks and grouts. There is also growing demand for \MP use in semiconductor fabrication and
lithium ion battery manufacturing. Data reported for llie 2' > 16 CDR period ( ) indicate
over 160 million pounds of NMP were manufactured (including imports) in the United States in 2015
(I ).
NMP is used in paint removers, and as a sol\ enl reagent for the electronics and pharmaceutical
industries. It is also used as a solvent for hydrocarbon recovery in the petrochemical processing industry,
and for the desulfurization of natural gas (Global Newsw ' J5; Fft H;; )15). While paint removers
represent a large product category for NMP, growth in this sector is uncertain as a result of the potential
risks identified in the previous risk assessment published by EIW ( ; PA. 2015).
NMP is a key cleaning component lor the manufacture of semiconductors used in electronics, and for
the manufacture of printed circuit boards As the consumer demand for electronics rises, especially in
the Asia Pacific region, the global demand lor NMP is expected to grow. Similar increases in NMP use
may occur in other regions, albeit to a lesser degree (•.1 View Research. 2016). The U.S. market
revenue for NMP is also expected to increase over the next ten years despite variations in the oil and gas
industry NMP is primarih used in downstream processes, which makes it more resilient to market
volatility in this sector ( , 2016).
1.2.2 Toxics Release Inventory Data
Under the Emergency Planning and Community Right-to-Know Act (EPCRA) Section 313, NMP is a
TRI-reportable substance effective January 1, 1995. During problem formulation, EPA further analyzed
the TRI data and examined the definitions of elements in the TRI data to determine the level of
confidence that a release would result from specific types of land disposal (e.g., RCRA Subtitle C
hazardous landfill and Class I underground Injection wells) and incineration. EPA also examined how
NMP is treated at industrial facilities.
Table 1-3 provides production-related waste management data for NMP reported by industrial facilities
to the TRI program from reporting years 2015 to 2017.1 In reporting year 2017, 380 facilities reported a
1 Reporting year 2017 is the most recent TRI data available. Data presented in Table 1-3 and Table 1-4 were queried using
TRI Explorer and uses the 2017 National Analysis data set (released to the public in October 2018). This dataset includes
revisions for the years 1988 to 2017 processed by EPA.
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total of approximately 274 million pounds of NMP production-related waste. Of this total amount,
roughly 245 million pounds were recycled, 7 million pounds were recovered for energy, 10 million
pounds were treated, and 10 million pounds were disposed of, or otherwise released to the environment.
Table
-3. Summary of NMP TRI Production-Related Waste
Managed from 2015-2017 (lbs)
Year
Number of
Kacililies
Recycling
Knergy
Recovery
Treatment
Releases
ii.h.t-
Total Production
Related Waste
2015
396
197,244,994
7,129,521
15,607,662
S.S24.7S2
228,806,960
2016
398
193,273,808
7,833,440
14,466,669
1UJ2U. 11)5
225,694,022
2017
380
245,436,619
7,397,866
10,468,156
10,420,124
273,722,765
Data source: 2015-2017 TRI Data fUndated October 2018) ("U.S. EPA. 2G17f).
a Terminology used in these columns may not match the more detailed data element names used in the TRI public data and
analysis access points.
b Does not include releases due to one-time events not associated w illi production such as remedial actions or earthquakes.
0 Counts all releases including release quantities transferred and release quantities disposed of by a receiving facility
reporting to TRI.
Table 1-4. provides a summary of NMP releases to the environment reported to TRI for the same
reporting years as Table 1-3.1 Approximately 19.053 pounds of NMP water releases, 1,532,507 pounds
of NMP air releases, and roughly 7,548,997 pounds of NMP land releases were reported to TRI in 2017.
In addition to the quantities reported as in Tahle 1-4 as "disposed ofin Class I underground injection
wells and Resource Conservation and Recovery Act (RCRA) Suhiille C landfills", the reported land
disposal techniques included; disposal to landfills other than RCRA Subtitle C (1,920,162 pounds),
Class II-V underground injection wells (12,115 pounds), land treatment/application farming (3,571
pounds), RCRA Subtitle C surface impoundments (73 pounds), and other land disposal such as waste
piles, spills and leaks (12.521 pounds):
Table 1-4. Summary of NMP TRI Releases to the Knvironment from 2015-2017 (lbs)
Year
Nil in her
ol'
l-'iieililies
Air Releases
\\;i(er
Releases
l.iind Disposal
Oilier
Releases
.1
l ohil On-
iimi orr-
Siie
Disposal or
Oilier
Releases h'
Slack Air
Releases
l"iiiiili\e
Air
Releases
( hiss 1
I nder-
lirnund
Injection
RCRA
Subtitle
C
liiiuiriiis
All oilier
l.iind
Disposal ¦'
2015
396
XX". .()•>
54(>.H(i(i
14,092
T,.:r
2.737.671
228,099
8,132,388
1.4 ".370 d
6,456,827 d
2016
398
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b These release quantities do include releases due to one-time events not associated with production such as remedial
actions or earthquakes.
0 Counts release quantities once at final disposition, accounting for transfers to other TRI reporting facilities that ultimately
dispose of the chemical waste.
d Value shown may be different than the summation of individual data elements due to decimal rounding.
While production-related waste managed shown in Table 1-3 excludes any quantities reported as
catastrophic or one-time releases (TRI section 8 data), release quantities shown in Table 1-4 include
both production-related and non-routine quantities (TRI section 5 and 6 data) for 2015-2017. As a result,
release quantities may differ slightly and may further reflect differences in TRI calculation methods for
reported release range estimates ( 2017D.
1.3 Regulatory and Assessment History ______
EPA conducted a search of existing domestic and international laws, regulations and assessments
pertaining to NMP. EPA compiled the summary information provided in Table I -5 from data available
from federal, state, international and other government sources, as cited in Appendix A
Federal Laws and Regulations
NMP is subject to federal statutes or regulations, other than TSC.V thai are implemented by other
federal agencies/departments. A summary of federal laws, regulations and implementing authorities is
provided in Appendix A. 1
State Laws and Regulations
NMP is subject to state statutes or regulations A summary of stale laws, regulations and implementing
authorities is provided in Appendix A 2.
Laws and Regulations in Other Countries and International Treaties or Agreements
NMP is subject to statutes or regulations in countries other than the United States and/or international
treaties and/or agreements A summary of these laws, regulations, treaties and/or agreements is provided
in Appendix A 3
EPA idenlilied pre\ ious assessments conducted by other organizations (see Table 1-5). Depending on
the source, these assessments may include information on conditions of use, hazards, exposures and
potentially exposed or susceptible sub populations.
Tsihle 1-5. Assessment History of NMP
Authoring Or»;mi/;ition
Assessment
KPA Assessments
U.S. EPA, Office of Pollution Prevention and
Toxics (OPPT)
I m "A Work Plan Chemical Risk Assessment > •
Methylpyrrolidone: Paint Stripping Use CASRN
8 ( )
U.S. EPA, OPPT
Re-assessment of Pesticide Inert Ingredient
Exemption under the Food Quality Protection
Act fU.S. EPA.. 2006b}
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Authoring Organization
Assessment
Other I .S.-IJased Organizations
California Office of Environmental Health Hazard
Assessment (OEHHA)
* un-osition 65 Maximum Allowable Dose Level
1 < )
Internal ional
National Industrial Chemicals Notification and
Assessment Scheme (NICNAS), Australian
Government
i k-;nan Health Tie; H:. ..-¦¦¦.ssment (NICNAS.
2013)
Government of Canada, Environment Canada,
Health Canada
Draft Screening Asses of Risks to Human
a™ ^logical Receoi ( ironment Canada.
European Commission (EC), Scientific Commillcc
on Occupational Exposure Limits (OELs)
ation of Occupation,-! I: Limits for
' - (EC. 2016s)
Organisation for Economic Co-operation and
Development (OECD), Cooperative Chemicals
Assessment Program
.] ; £ • ial Assessme ...
(OECD )
World Health Organization (WHO) International
Programme on Chemical Safety (IPCS)
• oncise hemical Assessment
«,,.ment 35 T YLPYRROLIDONE
( )
Danish Ministry of the Environment
Environmental Protection Agency
Survey - Miliestvrelsen
(Danish ivumsirv of the Environment. 2015)
1.4 Scope of the Evaluation
1.4.1 Conditions of Use Included in the Draft Risk Evaluation
TSCA (I S C $ 3(4)) defines the conditions of use as "the circumstances, as determined by the
Administrator, under w liich a chemical substance is intended, known, or reasonably foreseen to be
manufactured, processed, distributed in commerce, used, or disposed of." The conditions of use are
described below in Table 1 -(¦>
Use categories i nclude the follow i ng: "industrial use" means use at a site at which one or more
chemicals or mixtures are manufactured (including imported) or processed; "commercial use" means the
use of a chemical or a mixture containing a chemical (including as part of an article) in a commercial
enterprise providing saleable goods or services; "consumer use" means the use of a chemical or a
mixture containing a chemical (including as part of an article, such as furniture or clothing) when sold to
or made available to consumers for their use ( ).
To understand conditions of use relative to one another and associated potential exposures under those
conditions of use, Figure 1-1 depicts the life cycle diagram and includes the production volume
associated with each stage of the life cycle, as reported in the 2016 CDR reporting (U.S. EPA. ^ );
however, the life cycle diagram for NMP does not include specific production volumes because the
information was claimed as confidential business information (CBI).
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504 Additional worker monitoring data were provided to EPA during the public comment period for the
505 NMP problem formulation. This information was incorporated into the occupational exposure estimates
506 for semiconductor and electronics manufacturing.
507 Table 1-6. Categories and Subcategories of Conditions of Use Included in the Scope of the Draft
508 Risk Evaluation
l.il'e Cycle
Stage
Category "
Subcategory h
References
Manufacture
Domestic
Manufacture
Domestic Manufacture
i ¦¦ • M
Import
Import
}
Processing
Processing as a
reactant or
intermediate
Intermediate in Plastic Material
and Resin Manufacturing and in
Pharmaceutical and Medicine
Manufacturing
\
Public comments :A-HO-OPPT-
201 0 H 0010. mppt-
2'M , I. < . IO-V >PPT-
-16-0743-0017
Other
S. EPA. a
Incorporated
into
formulation,
mixture or
reaction
product
Adhesives and sealant chemicals
in Adhesive Manufacturing
EPA. (201 K Market profile
11 - in h. • " ,
Public comments EPA-HO-OPPT-
2016-0743-0007. EP A-HO-OPPT-
2016-0743-0009. EP A-HO-OPPT-
_0I 7c), Market profile
Paint additives and coating
additives not described by other
codes in Paint and Coating
Manufacturing; and Print Ink
Manufacturing
1 S ' \ \ Market profile
H6-0743.
Public comments EPA-HO-OPPT-
2 0007. EPA-HO-OPPT-
2016-0743-0009. EPA-HO-OPPT-
o i:> Km
Plating agents and surface
treating agents in Fabricated
Metal Product Manufacturing
U.S. EPA. c
Incorporated
into
formulation,
mixture or
reaction
product
Processing aids not otherwise
listed in Plastic Material and
Resin Manufacturing
U.S. EPA. (2ot .1
Public comments EPA-HO-OPPT-
2016-0743-0015. EPA-HO-OPPT-
2016-0743-0017. EPA-HO-OPPT-
0035. EPA-HO-OPPT-
2016-0743-0038
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iIV Cycle
Slsi«e
CsiU'gorv "
SuhrsiU'gorv h
Uol'omuTs
Processing
Sol\ ents (for cleaning or
degreasing) in Non-Metallic
Mineral Product Manufacturing;
Machinery Manufacturing;
Plastic Material and Resin
Manufacturing; Primary Metal
Manufacturing; Soap, Cleaning
Compound and Toilet
Preparation Manufacturing;
Transportation Equipment
Manufacturing; All Oilier
Chemical Product and
Preparation Manufacturing.
Printing and Related Support
Activities; Services; Wholesale
and Retail Trade
. Market profile
1.6-0743.
Public comments EPA-HO-OPPT-
2) )010. EPA-HO-OPPT-
jo i o;ii iVs s,! r \ fl;
0027. *EPA-HO-OPPT-
0028
Solvents (v\ liich become part of
product formulation or nii\ture)
in Electrical I lt|Lii pinciil.
Appliance and Component
Manufacturing. Other
Manufacturing, Paint and
Coating Manufacturing; Print Ink
Manufacturing; Soap, Cleaning
Compound and Toilet
Preparation Manufacturing;
Transportation Equipment
Manufacturing; All Other
Chemical Product and
Preparation Manufacturing;
Printing and Related Support
Activities; Wholesale and Retail
Trade
(2 , Market profile
16-0743.
Public comments EP A-HO-OPPT -
EP A-HO-OPPT -
20
16-0743-0007
20
0009
20
16-0743-0010
20
16-0743-0011
20
16-0743-0019
20
0024
20
16-0743-0031
20
16-0743-0034
EPA-HO-QPPT-
EPA-HO-OPPT-
EPA-HO-Q]
EPA-HO-Q]
EP A-HO-OPPT -
Processing
Incorporated
into
formulation,
Surface active agents in Soap,
Cleaning Compound and Toilet
Preparation Manufacturing
U * \ i JO I ,'c), Market profile
I 1.6-0743
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l-ifc Cycle
Slsi«e
CsiU'gorv "
SiihesiU'«orv h
UofomuTs
mixture or
reaction
product
Oilier uses in Oil and (ias
Drilling, Extraction and Support
Activities; Plastic Material and
Resin Manufacturing; Services
. Market profile
[ I* x 11- » - "in ''116-0743. Public
comment EP A-HO-OP
0743-0016
Incorporated
into article
Lubricants and lubricant
additives in Machinery
Manufacturing
: i, Market profile
EPA-HO-OPPT-2016-0743
Paint additives and coaling
additives not described by oilier
codes in Transportation
Equipment Manufacturing
U.S. EPA. a
Solvents (v\ liicli become part of
product formulation or mixture),
including in Textiles. Apparel
and Leather Manufacturing
EPA. (201 c).
Market Drofile EPA-HO-OPPT-
2" i >1" ! , Public comment EPA-
HO-OPPT-2016-0743-0027
Other, including in Plastic
Product Manufacturing
1 S 1 r \ >, Market profile
I ir 1 i|.t» - -iriri ¦¦ii-
-0067
Repackaging
W holesale and Retail Trade
! ? * f \L20l7c)
Recycling
Recycling
>017a U.S. EPA.
C . Public comments EPA-
r«* orpT-im • o r-ooi7.EPA-
HO-OPPT-2016-0743-0031
Distribution
in commerce
1 )i siri hution
1 )istribution in Commerce
I S J-T \ ! 2017f\ U.S. EPA.
O*l 1 Use document EPA.-H.0-
OPPT-2016-0743-0003
Industrial
commercial
and consumer
use
Paints and
coatings
Paint and coating removers
I S J-T \ 1.201 /c), Market profile
EPA-HO-OPPT-2016-0743. Public
comments EPA-HO-OPPT-2016-
0743-0008. EPA-H
<< t; r \ >i|l . ,
v«" I *< -i!01 \. 5 P VHO-03MM 201 -•
0743-0018. EPA-HO-OPPT-2016-
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l-ifc Cycle
Slsi«e
CsiU'gorv "
SiihesiU'«orv h
UofomuTs
0743-0025. EPA-HO-OPPT-2016-
0743-0035
Adhesive removers
Market profile EPA-HO-OPPT-
2 Public comments
HO-1 2016-0743-001 I. EPA-
ho-
Lacquers, stains, \arnishes.
primers and floor finishes
Market ni oil 1 e \.-HO-OPPT-
2 . Public comments
no «*ri \ -3-00is, 11» \
K H»ir. -u" i j -00 J i. FPA.
HO-OPPT-2016-0743-003 5
Powder coatings (surface
preparation)
Market profile EPA-HO-OPPT-
, Public comments I 1' \
OPPT-2016-0743-
Paint additives
and coating
additives not
described by
other codes
Paint additives
and coating
additives not
described In
oilier codes
Use in Computer and l-leclronic
Product Manufacturing.
Construction. I'alnicated Metal
Product Manufacturing,
Machinery Manufacturing, Other
Manufacturing, Paint and
Coating Manufacturing, Primary
Metal Manufacturing,
Transportation l-<.|iiipment
Manufacturing, Wholesale and
Retail Trade
EPA (201 /cl
Public comments EPA-HO-OPPT-
20 0006. EPA-HO-OPPT-
0007. EPA-HO-OPPT-
9. EPA-HO-OPPT-
2016-0743-0011. EPA-HO-OPPT-
:oi ooi«, \ r \ uo
_\m o s ooi., \ i \ «n>] k
2016-0743-0019. EPA-HO-OPPT-
2016-0743-0023. EPA-HO-OPPT-
0024. EP A-HO-OPPT -
0027. EP A-HO-OPPT -
^r\ a * oppt-
2016-0743-0032. EPA-HO-OPPT-
0035. EPA-HO-OPPT-
6. EPA-HO-OPPT-
3; EPA-HO-OPPT-
2016-0743-0064
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l-ifc Cycle
Slsi«e
CsiU'gorv "
SiihesiU'«orv h
UofomuTs
Industrial
commercial
and consumer
use
Sol\ cuts (lor
cleaning or
degreasing)
Isein l-lectiical l-quipmenl.
Appliance and Component
Manufacturing.
Public comments EP A-HO-OPPT-
2016-0743-0006. EPA-HO-OPPT-
2016-0743-0007. EPA-HO-OPPT-
0009. EPA-HO-OPPT-
3. EP A-HO-OPPT -
20 K 0024. EPA-HO-OPPT-
20 It 0027
Ink, toner and
colorant
products
Printer ink
U.S. '' "'"J, Use document,
EPA-HC ¦ 2016-0743-0003.
Public comments A-HO-OPPT-
2016-0743-.,,,., . lO-OPPT-
IO-OPPT-
Inks in writing equipment
" EPA (2 . Market profile
-HO-QPPT-2016-'"'' -I/-. Public
comment EPA-HO-OP
• '1
Processing aids,
specific to
petroleum
production
Petrochemical Manufacturing
U.S. EPA (1
Public comment. EPA-HO-OPPT-
2 0031
Adhesi\ es and
sealants
Adhesi\ es and sealant chemicals
including Mnding agents
U.S. EPA (1
EPA-HO-OPPT-2
comments EPA-H
0743-0006. EPA-
o*i* ooo ,iv\
0"4 '.-001 i, f'P\-
, Market profi
016-0743. Pu
O-OPPT-201
HO-OPPT-20
HO-OPPT-20
HO-OPPT-20
le
jlic
5-
16-
16-
0" r.-OOK ! P \ •
0743-0018. EPA-
HO-OPPT-20
HO-OPPT-20
16-
16-
23
Industrial
commercial
and consumer
use
Adhesi\ es and
sealants
Single component glues and
adhesives, including lubricant
adhesives
! ? * f \L20l7c)
EPA-HO-OPPT-2
comments EPA-H
0 i i, u \
, Market profi
016-0743. Pu
O-OPPT-201
HO-OPPT-20
le
jlic
5-
16-
o 11 oO s ,
HO-OPPT-20
16-
0"4 «-00J5, f'P\-
36
HO-OPPT-20
16-
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l-ifc Cycle
Slsi«e
CsiU'gorv "
SiihesiU'«orv h
UofomuTs
Two-component ulLies and
adhesives, including some resins
. Market profile
1 l* v 11- » - "in '-116-0743. Public
comments EPA-HO-OPPT-2016-
0' f.< 0011.! PA-H0-01V1M ;0i -•
O '1 -UO i «. .LI \ 1 {O-OPPT-2016-
C 8
Other uses
Soldering materials
Market nrofile EPA-HO-OPPT-
2 Public comments
EPA 2016-0743-0023
Anti-freeze and de-icing products
Automotive care products
U.S. EPA(2„.,.. . Public
comment,
EPA-HO-OPP1 743-0035
Lubricants and greases
EPA. (1
Metal products not
covered elseu here
i>0l7c),
Public comment,
EPA-HO-OPPT-2016-0743-0027.
EP A-HO-OPPT-2016-0743-0028
Public comment. EPA-HO-OPPT-
2 0027. EPA-HO-OPPT-
8
1 .ahoralory chemicals
U.S. EPA. (1
Public comments EPA-HO-OPPT-
2016-0743-0007. EPA-HO-OPPT-
0009
Industrial
commercial
and consumer
use
()ther uses
Lithium ion batteries
Market profile EPA-HO-OPPT-
. Public comment EPA-
W16-0743-0005
Cleaning and furniture care
products, including wood
cleaners, gasket removers
Market profile EPA-HO-OPPT-
201.6-0743. Public comment EPA-
Z016-0743-0025. EPA-
HO-OPPT-2016-0 743-003 5
Other uses in Oil and Gas
Drilling, Extraction and Support
Activities c
U.S. EPA (2
Lubricant and lubricant additives,
including hydrophilic coatings
Market profile EPA-HO-OPPT-
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l-ifc Cycle
Slsi«e
CsiU'gorv "
SiihesiU'«orv h
UofomuTs
Fertilizer and other agricultural
chemical manufacturing -
processing aids and solvents
Public comment EP A-HO-OPPT-
2016-0743-0010. EP A-HO-OPPT-
2016-0743-0036
Pharmaceutical and Medicine
Manufacturing - functional fluids
(closed systems)
1 ?"i
Public comment
I "PT-2016-0743-0031
Wood preservatives
Market profile " HO-OPPT-
2 , Public comment
EPA-HO-OPP1 023
Industrial pre-treatmenl
U.S. EPA (201711
Disposal
Disposal
Industrial wastewater treatment
j0 nil
U.S. EPA (201711
Publicly owned treatment works
(POTW)
Underground injection
1017f), Public comment
EP A-HO-OPPT-2016-0743 -0031
Landfill (municipal, hazardous or
other land disposal)
I S » V \ > 20! 7f). Public comment
EP A-HO-OPPT-2016-0743 -0031
1-missions to air
Incinerators (municipal and
hazardous waste)
a These categories of conditions of use appear in the life cycle diagram, reflect CDR codes and broadly represent NMP
conditions of use in industrial and/or commercial settings.
b These subcategories reflect more specific uses of NMP.
0 Industrial use added to reflect the use of NMP in products in the Oil and Gas Drilling, Extraction This addition to the risk
evaluation will help ensure that EPA determines whether NMP presents an unreasonable risk "under the conditions of use,"
TSCA 6(b)(4)(A).
509
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510
MFG/IMPORT
PROCESSING
Manufacturing
(Includes Import)
(161 million lbs)
Processing as
Reactant/lntermediate
(Volume CBI)
e.g., high-temperature polymers
Incorporated into
Formulation, Mixture, or
Reaction Products
(> 3.08 million lbs)
e.g., paints,cleaners,adhesives
Incorporated into Article
(>170,000 lbs)
e.g., ma ch i nery, p I a sti cs, texti I es
Repackaging
(Volume CBI)
e.g., wholesale and retail trade
511
512
513
514
515
516
517
518
Recycling
e.g., recovered and
reclaimed solvents
INDUSTRIAL, COMMERCIAL, CONSUMER USES a
~
RELEASES and WASTE DISPOSAL
Paints and Coatings
(>728,000 lbs)
e.g., paint removal
Solvents for Cleaning and
Degreasing
(>521,000 lbs)
e.g., photoresistremoval/cleaner,
sea I a nt remover, cl ea ner, a erosol
foaming cleaner
Ink, Toner and Colorant products
(181,000 lbs)
e.g., pri nter i nk
Processing Aids, Specific to
Petroleum Production
(>3,080 lbs)
Adhesives and Sealants
(>1,760 lbs)
e.g., adhesive,automotive seam sealer
Other Uses
e.g., I a boratory chemica Is; fa brie, texti I e
and leather products; arts,crafts and
hobby materia Is;toys, playground a nd
s porti ng goods/equ i p ment
Disposal
See Figure 2-4 for Environmental Releases and
Wastes
~ Ma nufacturing (incl udes import)
~ Processing
~ Uses
Figure 1-1. NMP Life Cycle Diagram
The life cycle diagram depicts the conditions of use that are considered within the scope of the draft risk evaluation during various life
cycle stages including manufacturing, processing, distribution, use and disposal. The production volumes shown are for reporting year
2015 from the 2016 CDR reporting period (U.S. EPA. 2017c). Activities related to distribution (e.g., loading, unloading) will be
considered throughout the NMP life cycle, rather than using a single distribution scenario.
a See Table 1-6 for additional uses not mentioned specifically in this diagram.
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1.4.2 Conceptual Model
EPA considered the hazards that may result from exposure pathways outlined in the preliminary
conceptual models of the NMP Scope document (U.S. EPA. 201 Td). These conceptual models
considered potential exposures resulting from consumer activities and uses, industrial and commercial
activities, environmental releases and waste disposal. During problem formulation EPA modified the
initial conceptual models provided in the NMP Scope document based on reasonably available
information identified for NMP (U.S. EPA. 2018c). For reasons described below, the oral route of
exposure was removed from the conceptual model for consumer activities and uses.
During risk evaluation, EPA considered oral exposures that may result from consumer use of NMP -
containing products (e.g., infant mouthing behaviors). EPA reviewed experimental product-testing
information on NMP content in consumer articles and determined which products are likely to be
mouthed (e.g., blankets, toys). EPA then identified information sources that measured NMP content in
various consumer products and considered additional contextual information regarding product use,
including the extent of NMP migration from these products. Based on this information, the potential for
consumer exposure via the oral route is expected to be negligible; therefore, this exposure pathway will
not be further analyzed.
The conceptual model presented in the NMP Problem Formulation also listed dust as potential NMP
exposure pathway for consumers. There is limited information a\ ailable on NMP levels in dust, but EPA
expects the impacts of this uncertainty to be negligible, as this exposure source is encompassed within
the conservative estimates derived for dermal and inhalation exposures i:onment Canada. 2017).
Lastly, EPA did analyze NMP exposures to bystanders (i e . those located near consumers during use)
who do not have direct contact with WIP-containing consumer products. Though EPA's 2015 Paint
Remover risk assessment showed no risks to bystanders from indirect exposure to NMP air
concentrations associated with consumer use, the supplemental paint remover analysis in the risk
assessment consisted of several scenarios resulting in high NMP air concentrations that could expose
other individuals in the home (see M 2) ( ^ ). Given the evaluation of a greater number of
conditions of use in addition to paint removers, EIW estimated NMP exposures to bystanders.
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INDUSTRIAL AND COMMERCIAL
ACTIVITIES / USES
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EXPOSURE PATHWAY EXPOSURE ROUTE RECEPTORS e
HAZARDS
Manufacturing
Processing:
~ As reactant/
intermediate
• Incorporated into
formulation, mixture, or
reaction product
• Incorporated intoarticle
~ Repackaging
Recycling
Paints and Coatings
e.g., paint removal9
Solvents for Cleaningand
Degreasing
Inks,Toner andColorant
Products
Processing Aids, Specific
Petroleum Production
Adhesives and Sealants
Other Uses b
^ Waste Handling, i
Treatment and Disposal
J _j^ Wastewater,, Liquid '
(See Figure 1-4}
Figure 1-2. NMP Conceptual .Model for industrial and Commercial Activities and Uses: Potential Exposures and Hazards
The conceptual model presents exposure pathways, routes and hazards to human receptors from industrial and commercial uses of NMP.
a U.S. EPA (20.1.5) assessed NMP use mi paint removal; these uses will be considered during risk evaluation to ensure previous assessments are aligned with the
Procedures for Chemical Risk Evaluation under the Amended Toxic Substances Control Act (40 CFR Part 702).
b Some products are used in both commercial and consumer applications. Additional uses of NMP are included in Table 1-6.
0 Emissions to outdoor air include stack emissions and fugitive emissions such as fugitive equipment leaks from valves, pump seals, flanges, compressors, sampling
connections and open-ended lines; evaporative losses from surface impoundment and spills; and releases from building ventilation systems.
dOral exposure via incidental ingestion of inhaled \ apor/mist will be considered as an inhalation exposure.
e Receptors include potentially exposed or susceptible subpopulations.
f When data and information are available to support the analysis, EPA expects to consider the effect that engineering controls and/or personal protective equipment
have on occupational exposure levels.
Workers
Occupational
Non-Users
Inhalation d
Liquid Contact
Vapor/ Mist
Dermal
Outdoor Airc
(See Figure 2-4 for
Emissionsto Air)
H.izards Potentially Associated with
Acute and/or Chronic Exposures
KEY:
GravTexi: Sources/Media/Receptors that will
not be further analyzed
~ Pathways that will befurther analyzed
Pathways that will not be further
analyzed
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CONSUMER ACTIVITIES/USES EXPOSURE PATHWAY EXPOSURE ROUTE RECEPTORS® HAZARDS
562
563
564
565
566
567
568
569
570
Solvents for Cleansngand
De-greasing
Adhesive* and Sealants
Paints end Coatings 3
e.g., paint removal
Ink, loner, and Colorant Products
e.g., printer ink
Other Usesb
e.g., arts, crafts and hobby
materials
-J* Liquid Contact
^ Vapor/Mist/Dust
p Dermal
Consumers
Orald
-~( Bystanders
inhalation
Hazards Potentially Associated
with Acute Exposures;
See Section 2.4.2
Consumer HandUngand Disposal
of Waste -
Liquid Contact
Vapor/Mist/Dust
Wastew-aier, Liquid Wastes, Solid Wastes
(See Figure 2-4}
Dermal
Consumers
Oral*
Bystanders
Inhalation
KEY:
Sources/Med^a/Receptors that will
not be further analyzed
Pathways that wsfi be further analyzed
Pathways that will not be further
analyzed
Figure 1-3. NMP Conceptual Model for Consumer Activities and Uses: Potential Exposures and Hazards
The conceptual model presents ihe exposure pathways, routes and hazards to human receptors from consumer activities and uses of NMP.
a U.S. EPA (20.1.5) assessed NMP use in paint and coatinu removal; these uses will be considered during risk evaluation to ensure previous assessments are aligned
with the Procedures for Chemical Risk Evaluation under llio Amended Toxic Substances Control Act (40 CFR Part 702).
b Some products are used in both commercial and consumer applications; additional uses of NMP are included in Table 1-6.
0 Consumers may also be exposed while handling municipal wastes; however, the pathway is uncertain.
d Oral exposure via incidental ingestion of inhaled v apor/mist/dust will be considered as an inhalation exposure.
e Receptors include potentially exposed or susceptible subpopulations.
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RELEASES AND WASTES FROM EXPOSURE PATHWAY EXPOSURE ROUTE RECEPTORS' HAZARDS
INDUSTRIAL / COMMERCIAL / CONSUMER USES
Industrial Pre-
Treatment or
Industrial WWT
Indirect discharge
Wastewater or
Liquid Wastes a
POTW
Underground
Injection
Municipal,
Hazardous Landfi
or Other Land
Disposal
;.v
' V
Solid Wastes
. .
Incinerators
(Municipal &
Hazardous Waste)
Liquid Wastes
Off-site Waste
Transfer
WasteTra us p
Recycling, Other
Treatment :1
KEY:
: Sources/Media/Receptors thatwill notbe
Emissions to Air
Pathways that will be further analyzed
Pathways that will notbe further analyzed
Figure 1-4. NMP Conceptual Model I'or Environ mental Releases and Wastes: Potential Exposures and Hazards
The conceptual model presents the exposure pathways, routes and hazards to human and environmental receptors from NMP environmental releases.
a Industrial wastewater or liquid wastes m;i\ he lie;iied on-siie ;md then released to surface water (direct discharge), or pre-treated and released to POTW (indirect discharge).
For consumer uses, such wastes may be released directly lo POTW (i.e., down the drain). Drinking water will undergo further treatment in drinking water treatment plant.
Ground water may also be a source of drinking waier
b Additional releases may occur from recycling and oilier u ;iste treatment.
0 Volatilization from or contact with NMP-containing drinking/tap water during showering, bathing and washing represents another potential exposure pathway.
d Presence of mist is unlikely; inhalation and oral exposure are expected to be negligible.
e Receptors include potentially exposed or susceptible subpopulations.
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EPA did not include pathways under programs of other environmental statutes, administered by
EPA for which long-standing regulatory and analytical processes already exist. For example,
EPA does not consider on-site NMP land releases that are disposed via underground injection in
the risk evaluation. Most of the on-site land disposal reported for NMP in the 2015 TRI was to
Class I underground injection wells (approximately 3.6 million pounds), with no reported
environmental releases via underground injection to Class II-VI wells ( ).
Environmental disposal of NMP via injection into Class I wells is managed and prevented from
further environmental releases by RCRA and Safe Drinking Water Act (SDWA) regulations.
Therefore, disposal of NMP via underground injection is not likely to result in environmental
and general population exposures.
During problem formulation, EPA used information reported in EPA's Toxics Release Inventory
(TRI) to predict NMP surface water concentrations near facilities reporting the largest discharges
to water. NMP surface water concentrations were estimated using conservative assumptions with
EPA's Exposure and Fate Assessment Screening Tool, Version 2014 (E-FAST 2< > 14) TRI water
releases for the top 12 facilities reporting NMP releases and the associated estimates of NMP
surface water concentrations estimated in the NMP Problem I ormulation (U.S. EPA, 20 i 8c) are
shown in Appendix D.
EPA identified a low risk concern for NMP exposure lo aquatic organisms based on the TRI
reported discharges of NMP to surface waters To capture "high-end" surface water
concentrations, EPA compiled the release data for six Iaci lilies that reported the largest NMP
direct water releases. This represented > 99% of the total \ olume of NMP reported as a direct
discharge to surface water during the 2015 TRI reporting period. Comparing these "high-end"
surface water concentrations with l tie respective concentrations of concern identified for aquatic
organisms indicate a low risk concern (see Table 4-1). EPA does not anticipate a risk concern for
environmental receptors from NMP releases to surface water.
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1.5 Systematic Review
TSCA requires EPA to use scientific information, technical procedures, measures, methods,
protocols, methodologies and models consistent with the best available science and base
decisions under Section 6 on the weight of scientific evidence. Within the TSCA risk evaluation
context, the weight of the scientific evidence is defined as "a systematic review method, applied
in a manner suited to the nature of the evidence or decision, that uses a pre-established protocol
to comprehensively, objectively, transparently, and consistently identify and evaluate each
stream of evidence, including strengths, limitations, and relevance of each study and to integrate
evidence as necessary and appropriate based upon strengths, limitations, and relevance" (40
C.F.R. 702.33).
To meet the TSCA § 26(h) science standards, EPA used the TSCA systematic review process
described in the Application of Systematic Review in TSCA Risk Evaluations document (U.S.
18a). The process complements the risk evaluation process in that the data collection,
data evaluation, and data integration stages of the systematic review process are used to develop
the exposure and hazard assessments based on reasonably a\ ailahlc information. EPA defines
"reasonably available information" to mean information that N\\ possesses, or can reasonably
obtain and synthesize for use in risk evaluations, considering the deadlines for completing the
evaluation (40 C.F.R. 702.33).
EPA is implementing systematic review methods and approaches within the regulatory context
of the amended TSCA. Although EPA will make an effort to adopt as many best practices as
practicable from the systematic review community. V.IW expects modifications to the process to
ensure that the identification, screening, evaluation and integration of data and information can
support timely regulatory decision making under the aggressive timelines of the statute.
1.5.1 Data and In formal ion Collection
EPA planned and conducted a comprehensive literature search based on key words related to the
discipline-specific evidence supporting the risk evaluation (e.g., environmental fate and
transport, engineering releases and occupational exposure; exposure to general population,
consumers and environmental exposure; and environmental and human health hazards). EPA
then developed and applied inclusion and exclusion criteria during the title and abstract
screening to identify information potentially relevant for the risk evaluation process. The
literature and screening strategy as specifically applied to NMP is described in the Strategy for
Conducting Literature Searches for NMP: Supplemental File to the TSCA Scope document (U.S.
); results of the title and abstract screening process are published in the N-
Methylpyrrolidone a \SRS H72-50-4) Bibliography: Supplemental File to the TSCA Scope
Document (IIS &).
For studies determined to be on-topic after title and abstract screening, EPA conducted a full text
screening to further exclude references that were not relevant to the risk evaluation. Screening
decisions were made based on eligibility criteria documented in the form of the populations,
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exposures, comparators, and outcomes (PECO) framework or a modified framework3. Data
sources that met the criteria were carried forward to the data evaluation stage. The inclusion and
exclusion criteria for full text screening for NMP are available in Appendix G of the NMP
Problem Formulation document (U.S. EPA. 2018c).
In addition to the comprehensive literature search and screening process described above, EPA
leveraged information presented in previous assessments4 when idenlilying relevant key and
supporting data5 and information for developing the NMP draft risk evaluation This is discussed
in the Strategy for Conducting Literature Searches for NMP: Supplemental / document to the
TSCA Scope document ( ). In general, many of the key and supporting data
sources were identified in the NMP (CASRN 872-50-4) Bibliography: Supplemental File for the
TSCA Scope Document (U.S. EPA. 2017b). However, there were instances where EPA missed
relevant sources that were not captured in the initial categorization of the on-topic references.
EPA found additional data and information using backward reference searching, a technique that
will be included in future search strategies. This issue was discussed in Section 4 of the
Application of Systematic Review for TSCA Risk F * "iom(\ Ml 8a). Other relevant
key and supporting studies were identified througli targeted supplemental searches conducted to
inform the analytical approaches and methods used in the NMP draft risk evaluation (e.g., to
identify specific information needed for exposure modeling) or to identify new information
published after ill e date of the initial search.
EPA used previous chemical assessments to quickly identify relevant key and supporting studies
in order to expedite the data quality e\ aluation of these data sources, but many were already
captured in the comprehensive literature search strategy described above. EPA also considered
newer information not co\ ered by previous chemical assessments, as described in the Strategy
for ('onducting I iieramre Searches for NMP: Supplemental Document to the TSCA Scope
docmiieni (U.S. ,...... ) EPA then evaluated the confidence of this information rather than
evaluating the confidence of all underlying evidence ever published on NMP fate and transport,
environmental releases, and environmental and human exposure and hazard potential. Such a
comprehensi\ e evaluation would be extremely labor intensive and could not be achieved under
the TSCA statutory deadlines for most chemical substances, especially those that are data rich.
EPA also considered how this approach to data evaluation would change the conclusions
presented in previous assessments.
Using this pragmatic approach, EPA maximized the scientific and analytical efforts of other
regulatory and non-regulatory agencies by accepting for the most part, the relevant scientific
3 A PESO statement was used during the full text screening of environmental fate and transport data sources. PESO
stands for Pathways and Processes, Exposure, Setting or Scenario, and Outcomes. A RESO statement was used
during the full text screening of the engineering and occupational exposure literature. RESO stands for Receptors,
Exposure, Setting or Scenario, and Outcomes.
4 Examples of existing assessments are EPA's chemical assessments (e.g. previous work plan risk assessments,
problem formulation documents), ATSDR's Toxicological Profiles, EPA's IRIS assessments and ECHA's dossiers.
This is described in more detail in the Strategy for Conducting Literature Searches for 1,4-Dioxane: Supplemental
File for the TSCA Scope Document (https://www.epa.gov/sites/production/files/2017-06/documents/14-
dioxane lit search strategy 0530.17.pdf).
5 Key and supporting data and information are those that support key analyses, arguments, and/or conclusions in the
risk evaluation.
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knowledge gathered and analyzed by others, except for influential information sources that may
impact the weight of the scientific evidence underlying EPA's risk findings. This influential
information (i.e., key/supporting studies) came from a smaller pool of information sources
subjected to the rigor of the TSCA systematic review process to ensure that the best available
science is incorporated into the weight of the scientific evidence used to support the NMP draft
risk evaluation.
The literature flow diagrams shown in Figures 1-5, 1-6, 1-7, 1-8, and 1-9 highlight the results
obtained for each scientific discipline based on this approach. Each diagram provides the total
number of references considered at the start of each systematic re\ ieu stage (i.e., data search,
data screening, data evaluation, data extraction/data integration) and those excluded based on the
criteria guiding EPA's screening and data quality evaluation decisions.
EPA made the decision to bypass the data screening step for data sources that were highly
relevant to the draft risk evaluation as described abo\ e These data sources are depicted as
"key/supporting data sources" in the literature flow diagrams. Note that the number of
"key/supporting data sources" were excluded from the total count during the data screening stage
and added, for the most part, to the data evaluation stage depending on the discipline-specific
evidence. The exception was the engineering releases and occupational exposure data sources
that were subject to a combined data extraction and evaluation step (I 'iuin e 1-6).
Data Extraction/Data Integration (n-10)
Key trusted studies
(n=l)
Data Search Results (n=2,372)
Data Screening (n=2,371)
Data Evaluation (n=ll)
Excluded References
(n=2,361)
Excluded: Ref that are
unacceptable based on the
evaluation criteria (n=l)
These are key and supporting studies from existing assessments (e.g., EPA IRIS assessments, ATSDR assessments, ECHA
dossiers) that were highly relevant for the TSCA risk evaluation. These studies bypassed the data screening step and
moved directly to the data evaluation step.
Figure 1-5. Key/Supporting Data Sources for Environmental Fate and Transport
The number of publications considered in each step of the systematic review of the NMP fate
and transport literature is summarized in Figure 1-5. Literature on the environmental fate and
transport of NMP were gathered and screened as described in Appendix C of the Application of
Systematic Review in TSCA Risk Evaluations ( i). Additional information
regarding the literature search and screening strategy for NMP is provided in EPA's Strategy for
Conducting Literature Searches for N-Methylpyrrolidone (NMP): Supplemental File to the TSCA
Scope Document (U.S. EPA. 2017e). The results of this screening are published in the NMP
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(CASRN 872-50-4) Bibliography: Supplemental File to the TSCA Scope Document (U.S. EPA.
2017b).
Data Search Results in* 2,419)
Data Scretniflg (n« 2,419)
Data Extraction.'Data Evaluation tn«
105)
,1= 2
Data Integration jn« 60)
asse
i
Figure 1-6. Key/Supporting Sources for Releases and Occupational Exposures
As shown in Figure 1-6, the literature search strategy for NMP environmental releases and
occupational exposures yielded 2.41 ^ data sources. Of these, 70 data sources were determined to
be relevant to the NMP draft risk c\ alualion during the data screening process. These relevant
data sources progressed to the data extraction/evaluation phase. After data extraction/evaluation,
EPA identified several data gaps and performed a supplemental, targeted search to fill these gaps
(e.g. to locate information needed for exposure modeling). This supplemental search yielded 35
relevant data sources that bypassed the initial data screening step. These new data sources were
added to the 70 data sources originally determined to be relevant during the data screening
process; all were evaluated and extracted in accordance with the process described in Appendix
D of the Application of Systematic Review in TSCA Risk Evaluations document (U.S. EPA.
2018a). Of the 105 sources evaluated, 6 were rated as containing only unacceptable data based
on serious flaws detected during data evaluation. Of the 99 sources considered for data
integration, 39 were not integrated based on EPA's integration approach (i.e., higher quality data
were used). Data from the remaining 60 sources were integrated into the NMP draft risk
evaluation.
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n=22
Data Evaluation (n=22 J
Excluded References >n=f10)
Data Search Resit Is (n=!32J
Excluded: Ref that are
unacceptable based on
evaluation criteria (n=1)
Data Extraction/Data Integration (n-21)
Data Screening |n=13Z;
•Any relevant studies from prior assessments that were identified as potentially relevant for TSCA assessment
needs bypassed the data screening step and moved directly to the data evaluation step (e.g. key/supporting
studies from IRiS assessments, AT SDR assessments, ECHA dossiers, etc.).
Figure 1-7. Key/Supporting Sources for General Population. Consumer and Environmental
Exposures
The number of data and information sources considered in each step of the systematic review of
NMP literature on general population, consumer and environmental exposure is summarized in
Figure 1-7. The literature search results for general population, consumer and environmental
exposures yielded 132 data sources. Of these data sources, 22 were determined to be relevant to
the NMP draft risk evaluation through the data screening process. These relevant data sources
were evaluated in accordance with . l/>/v//
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Excluded References due to
ECOTOX Criteria
Key/Supporting
Studies
(n = 5)
Excluded References due to
ECOTOX Criteria
(n = 12)
Data Extraction I Data Integration (n = S)
Data Evaluation (n = 9]
Full Text Screening (n - 16)
Excluded References that are
unacceptable based
on evaluation catena and/or are
out of scope
(n-4)
Data Search Results frt = 719)
Title/Abstract Screening (n = 714)
Figure 1-8. Key/Supporting Data Sources for Environmental Hazards
The environmental hazard data sources for NMP were identified through literature searches and
screening strategies using the I X'OTOXicolouy knowledgebase system (ECOTOX) Standing
Operating Procedures For studies determined to be on-topic after title and abstract screening,
EPA conducted a lull text screening to further exclude citations that were not considered relevant
to the NMP draft risk e\ aluation. Screening decisions were made based on eligibility criteria as
documented in the ECOTOX I ser (iuide (> J.S. EPA. 2018b)). Additional details can be found in
the Strategy for Conduct mI iteraiiire Searches for NMP: Supplemental Document to the TSCA
Scope / h)ciiment (U.S. ).
The literature search strategy lor environmental hazard data identified 719 citations for NMP
Figure 1-8). At the title and abstract screening phase, 698 of these citations were excluded as
"off-topic" based on NWs ECOTOX knowledgebase criteria. The remaining 16 citations
underwent a more thorough (full-text) screening process using the same ECOTOX criteria to
determine which should proceed to data evaluation. Several citations were determined to be "out
of scope" during the initial screening steps and were therefore excluded from data evaluation.
Five "Key/Supporting Citations" for Environmental Hazard were identified by EPA as a result of
a review of the OECD HPV S1DS Document for NMP ( 09b). EPA obtained the full
study reports from BASF and GAF (only summaries are provided in the OECD document). Of
these five citations, three were translated from German. These five citations were found
independently from the ECOTOX process.
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EPA developed data quality evaluation criteria based on a combination of EPA's
ECOTOXicology knowledgebase (ECOTOX) criteria and the Criteria for Reporting and
Evaluating ecotoxicity Data (CRED), as discussed in the Applications of Systematic Review for
TSCA Risk Evaluations (U.S. EPA. 2018a). Nine citations went through the data evaluation
process using the data quality evaluation criteria for NMP. EPA analyzed each individual
toxicity study in each of these citations using the data quality evaluation to determine the overall
study quality. Four citations were excluded during data evaluation. In total, five citations were
evaluated for data extraction/integration in the NMP draft risk evaluation.
Data S#sich Results in = 1,39?)
Key&up porting data
sowoes
(ft = 3)
~J Exduded References (n = 1361)
Data Screening tn * 1.J94)
n=33
Excluded: Ref thai are
unaccopt&Dte fcasetS on
evaluation criteria (b = 3}
Data Evaluation in - 38i
Data Extract>o» Data nuegratson (n
•Any relevant studies torn prior assessments that wee identified as potentially re lev an: for TSCA assessment
needs bypassed the data screening step ami moved directy to lie data evaluation step (e.g. key/supporting
slides from IRIS assessment, ATSDR assessments. ECHft testers, etc.).
Figure 1-9. Literature Flow Diagram for Human Health Key/Supporting Data Sources
The literature search strategy used to gather human health hazard information for NMP yielded
1,397 studies. This included three key and supporting studies (identified from previous
regulatory assessments) that skipped the initial screening process and proceeded directly to the
data evaluation phase. Of the 1,394 studies identified for NMP, 1,361 were excluded as off topic
during the title and abstract screening phase. The remaining 36 human health hazard studies
advanced to full text screening; 33 were determined to be relevant to the NMP draft risk
evaluation. These relevant data sources were evaluated and extracted in accordance with the
process described in Appendix G of the Application of Systematic Review in TSCA Risk
Evaluations Document (U.S. EPA. 2018a). Additional details can be found in EPA's Strategy for
Conducting Literature Searches for N-Methylpyrrolidone (NMP): Supplemental File to the TSCA
Scope document (U.S. EPA. 2017e). The results of this screening process are published in the
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NMP (CASRN 872-50-4) Bibliography: Supplemental File to the TSCA Scope Document (
I 17b).
1.5.2 Data Evaluation
During the data evaluation stage, EPA assessed the quality of the data sources using the
evaluation strategies and criteria described in the Application of Systematic Review in TSCA Risk
Evaluations (U.S. EPA. 2.018a), EPA evaluated the quality of all data sources that passed full-
text screening. Each data source received an overall confidence rating of high, medium, low or
unacceptable.
The results of the data quality evaluations are summarized in Sections 2 I (Fate and Transport),
2.2 (Releases to the Environment), 2.3 (Environmental Exposures). 2 4(1 In man Exposures), 3.1
(Environmental Hazards), and 3.2 (Human Health Hazards). Supplemental files I A-1H (see list
of supplemental files in Appendix B) also provide details of the data evaluations including
individual metric scores and the overall study score lor each data source.
1.5.3 Data Integration
Data integration includes analysis, synthesis and integration of information for the risk
evaluation. During data integration, EPA considers quality., consistency, relevance, coherence
and biological plausibility to make final conclusions regarding the weight of the scientific
evidence. As stated in the Application of Systematic Review in ISCA Risk Evaluations (U.S.
E 18a). data integration involves transparently discussing the significant issues, strengths,
and limitations as well as the uncertainties of the reasonably a\ ailable information and the major
points of interpretation ( '18< )
EPA used previous assessments to identify key and supporting information and then analyzed
and synthesized available lines of evidence regarding NMP's chemical properties, environmental
fate and transport properties and its potential for exposure and hazard. EPA's analysis also
considered recent data sources that were not considered in the previous assessments (Section
1.5.1) as well as reasonably a\ ailable information on potentially exposed or susceptible
subpopu lations
The exposures and hazards sections describe EPA's analysis of the relevant lines of evidence that
were found acceptable for the risk evaluation based on the data quality reviews provided in the
supplemental files.
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2 EXPOSURES
This section describes EPA's approach to assessing environmental and human exposures. First,
the fate and transport of NMP in the environment is characterized. Then, NMP environmental
releases are assessed. Last, this information is integrated into an assessment of occupational and
consumer exposures (including potentially exposed or susceptible subpopulations). For all
exposure-related disciplines, EPA screened, evaluated, extracted and integrated reasonably
available empirical data. In addition, EPA used models to estimate exposures. Both empirical
data and modeled estimates were considered when selecting values for use in the exposure
assessment.
The exposure pathways evaluated in the current assessment include dermal, vapor-through-skin
and inhalation. NMP is well absorbed following dermal exposures and dermal absorption
including NMP from the vapor phase typically contributes significantly to human exposure
(Bader et at. 2008; Keener et at.. 2007). NMP diluted in water has reduced dermal absorption
(Keener et at... 2007; Pay an et at.. 2003) while NMP diluted in other solvents, such as d-
limonene, can increase the absorption of NMP (Hut Sciences. 1998) and prolonged
exposures to neat (i.e., pure) NMP increases the pernieahililx of the skin (RIYM. 2013). NMP is
also absorbed via inhalation (Akesson and Paulsson. 19-' ) hul the low vapor pressure and mild
volatility can limit the amount of NMP available for inhalation I or nearby non-users, exposures
were limited to inhalation and vapor-through-skin exposure routes. In all cases, internal doses
integrating the different exposure routes were deri\ ed using a PBPk model.
The previously published PBPK model for \ \ IP ( ) was adapted for use by EPA
and described in Appendix T The model predicted absorption of liquid or vapor from the NMP
concentration, duration of contact and physiological descriptions such as body weight. The
physiological parameters of body weight and skin surface area used were specific to pregnant
women and women of childbearing age for acute exposures and to men for chronic exposures.
Absorption of NMP via inhalation depended on the NMP concentrations in air. Dermal
absorption of NMP depended on the NMP weight fraction in liquid, NMP vapor concentration
and skin surface area exposed to liquid and vapor. The thickness of the liquid film did not factor
directly into the estimate of liquid NMP absorption. As a conservative estimate for user scenarios
it was assumed that fresh material would be constantly deposited over the time of use such that
the concentration on the skin would remain essentially constant at the formulation concentration.
For example, a thin layer of compound is assumed to cover the surface area of the hands due the
activities of the condition use, which may include use of sponges or rags with either both hands
or one hand co\ ered for high end and central tendency, respectively. The exposure parameters
used to estimate internal NMP doses for the occupational and consumer exposure scenarios are
described below.
Exposure equations and selected values used in the exposure assessment are presented in the
following sections. More specific information is provided in Supplementary Files.
Following inclusion of NMP on EPA's TSCA Chemical Work Plan list in 2012, EPA published
an assessment of the human health risks associated with NMP use in paint and coating removal
( 2015) prior to passage of the Lautenberg Act amendments to TSCA. Since that time,
EPA has published the Scope (U.S. EPA. 2017d) and Problem Formulation (U.S. EPA. 2018c)
for the current risk evaluation.
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2.1 Fate and Transport
The environmental fate studies considered for this assessment are summarized in Table 2-1. This
information has not changed from that provided in the NMP Problem Formulation (U.S. EPA.
2018c).
2.1.1 Fate and Transport Approach and Methodology
Environmental fate data were evaluated using the environmental fate data quality criteria
outlined in the Application of Systematic Review in TSCA Risk Evaluations (; ",S. EPA. 2018a).
The study evaluation results are documented in the data evaluation tables presented in EPA-HQ-
OPPT-2019-0236. Environmental fate data from studies which met data quality requirements (as
indicated by high, medium, or low data quality scores) were extracted and integrated into the
current risk evaluation to characterize the environmental fate of NMP
EPA gathered and evaluated environmental fate information according to the process described
in the Application of Systematic Review in TSCA Risk l:.\ aluations (U.S. EPA. ).
Reasonably available environmental fate data were selected for use in the current evaluation.
EPA also used environmental fate and transport characteristics of NMP described in previous
regulatory and non-regulatory assessments to inform the en\ iron mental fate and transport
information discussed in this section and in Appendix C. EPA has high confidence in the
information used in the previous assessments to describe the em iron mental fate and transport of
NMP and thus used it to make scoping decisions
Although EPA conducted a comprehensive literature search and screening process as described
in Section 1.5, information reported in previous chemical assessments was also used to identify
key and supporting studies that could inform the current analysis (i.e., information supporting
key assumptions, arguments, and or conclusions). Where applicable, EPA also considered newer
information that was not considered in the previous chemical assessments. EPA did not critically
evaluate all underlying evidence ever published on the environmental fate and transport of NMP,
but instead focused its data evaluation efforts on key and supporting studies identified
previously, and any rele\ ant information identified subsequently. Using this pragmatic approach,
EPA maximized its o\\ n resources and the scientific and analytical efforts of other regulatory and
non-regulatory agencies In accepting lor the most part, the scientific knowledge gathered and
analyzed In others. As a result, a smaller pool of information was subjected to the TSCA
systematic re\ iew process to ensure that the NMP risk evaluation uses the best available science
to support the weight of the scientific evidence.
Please note that other data sources may be cited as part of the reasonably available evidence
presented on the fate and transport properties of NMP. For instance, EPA assessed the quality of
a study on the ready biodegradability of NMP (U.S. EPA. 20191) based on the data quality
criteria described in the Application of Systematic Review in TSCA Risk Evaluations (U.S. EPA.
2018a) and the study was determined to be of 'medium' confidence. Other fate estimates were
based on modeling results from EPI Suite™ (U.S. EPA. 2012c). a predictive tool for
physical/chemical and environmental fate properties. The data evaluation tables describing the
review of key and supporting fate data sources can be found in the supplemental document,
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Systematic Review Supplemental File: Data Quality Evaluation of Environmental Fate and
Transport Studies (1 'P \. _*<' i ).
The NMP physical-chemical properties and environmental fate characteristics used in the current
assessment are presented in Tables 1-1 and 2-1, respectively. EPA used EPI Suite™ estimations
and reasonably available fate data to characterize the environmental fate and transport of NMP.
During problem formulation, EPA also analyzed the air, water, sediment, land and biosolids
pathways. These results are described in the NMP Problem Formulation document (U.S. EPA.
2018c).
Environmental fate data from studies were evaluated using the en\ ironmental fate data quality
criteria outlined in The Application of Systematic Review in TSC IA Risk Evaluations (U.S. EPA...
2018a). The study evaluation results are documented in Appendix C. Environmental fate data
from acceptable studies were extracted and integrated during risk evaluation. Based on the
results obtained from the data quality evaluation process EPA has high confidence in the studies
used to characterize the environmental fate of NMP. The data extracted from environmental fate
studies are shown in Appendix C and the full environmental fate data quality ratings are
presented in the supplemental file (U.S. EPA. 2019).
NMP does not persist in the environmenl I pon release into the atmosphere, it is degraded via
reaction with photo-chemically produced hydroxy! radicals in ambient air. The half-life for this
reaction is approximately 5.8 hours, assuming a hydroxy I radical concentration of 1.5 x 106
hydroxyl radicals/cm3 air and a 12-hour day ( ) NMP is hygroscopic and can
dissolve in water droplets. Atmospheric releases may be remo\ ed by condensation or further
reaction with hydroxyl radicals
Although neat (pure) NMP is slightly volatile, volatilization from water and moist soils is not
likely based on its Henry's I.aw constant (3.2 x 10-9 atm m3/mole). NMP is not expected to
adsorb to suspended solids or sediment upon release to water due to its estimated soil organic
carbon/water partition coefficient (log koc <) '¦>). NMP exhibits high mobility in soil; hence,
environmental releases are expected to migrate from soil to ground water (U.S. EPA. 2012c).
I-PI Suite™ (U.S. EPA. ZU12< ) modules were used to predict volatilization of NMP from
wastewater treatment plants, lakes and rivers. The EPI Suite™ module that estimates chemical
remo\ al i n sew age treatment plants ("STP" module) was run to evaluate the potential for NMP
to biodegrade. \ olatilize to air or adsorb to sludge during wastewater treatment. The STP
module, using EJIOWTN predictions for biodegradation rates, estimates that most of NMP
releases to wastewater ( > 90%) will be removed by biodegradation. BIOWIN model predictions
further indicate negligible removal of NMP (< 1%) via adsorption to sludge or volatilization to
air. The EPI Suite™ input values are listed in Appendix C, Figured and the EPI Suite™
output are listed in the NMP Fate Supplementary Document ( ).
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Table 2-1. Environmental Fate Characteristics of NMP
Properly or
Kiulpoinl
\ ill lie ;|
Reference
Sluilv
Qiiiilily
Direct photo-
degradation
Not available
Indirect photo-
degradation
5.8 hours (estimated for atmospheric degradation)13
(
2012c)
High
Hydrolysis half-
life
Does not undergo hydrolysis
C
)
NA
Biodegradation
45% COD/2wks; (95% in 2weeks based on GC peak
disappearance) [aerobic in static die-away system
test, sewage sludge inoculum, OECD 3d 1 A]
( H
Ng. ' ')
High (1.37)
73% in 28 days (aerobic in water. Rcad\
Biodegradability, Modified Ministry of International
Trade and Industry (MITI), OECD 3< > 1 ( )
( ico
and
Regulatory
Affairs. 2.003)
Medium
(1.8)
Bioconcentration
factor (BCF)
3.16 (estimated)b
(U.S. EPA.
2012c)
High
Bioaccumulation
factor (BAF)
0.9 (estimated)13
(: .EPA..,
: . l£)
High
Soil organic
carbon ualcr
partition
coefficient (lou
Koc)
ii (estimated)'
(
2012c)
High
"Measured unless otherwise noicd
' lnforin;ilion \\;is estimated usiiiu 1 PI Suilo (U.S. iiPA, 20120)
N \ \nl applicable
The 1-I'l Suite™ module that estimates volatilization from lakes and rivers was run using default
settings lo e\ aluate the potential for NMP to volatilize from surface water. The model results
indicate thai \ olatilization from surface water is unlikely to be a significant removal pathway for
NMP. Aerobic biodegradation is expected to be the primary removal pathway for NMP in many
surface water en\ iionments based on measured data (see Table 2-1).
Experimental data and EP1 Suite™ model predictions indicate that NMP will degrade in aerobic
environments; however, the BIOWIN module within EPI Suite™ that estimates anaerobic
biodegradation potential (BIOWIN 7) ( 3191 2012c) predicts that NMP will not
rapidly biodegrade under anaerobic conditions. These model predictions are consistent with
previous assessments of NMP degradation potential (OECD. 2007b; Toxicology and Regulatory
Affairs. 2003: WHO. 2iml 1 r N"\ ! t how andNe. 1983V
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NMP exhibits low potential for bioaccumulation and bioconcentration in the environment.
Measured bioconcentration studies for NMP were not presented in EPA's previous evaluation of
risks associated with NMP use in paint and coating removal ( 015); however, based
on the estimated BAF and BCF values (0.9 and 3.16, respectively), NMP is not expected to
bioaccumulate or bioconcentrate in aquatic organisms (U.S. EPA. 2012c; OE 07b; U.S.
E ).
2.2 Releases to the Environment
Releases to the environment from conditions of use (e.g., industrial and commercial processes,
commercial or consumer uses resulting in down-the-drain releases) are one component of
potential exposure that may be derived from reported data obtained through direct measurement,
calculations based on empirical data and/or model assumptions.
Under the Emergency Planning and Community Righl-lo-Know Act (EPCRA) Section 3 13,
NMP has been a TRI-reportable substance effective January 1, 1995. The TRI database includes
information on disposal and other releases of NMP lo air. water, and land, in addition to how it is
managed through recycling, treatment, and burning lor energy recovery. EPA analyzed the TRI
data and examined the definitions of elements in the TRI data to determine the level of
confidence that a release would result from specific types of land disposal (i.e., RCRA Subtitle C
hazardous landfills and Class I underground injection wells) and incineration. EPA also
examined how NMP is treated at industrial facilities Based on 2d I 5 1'R.I reporting, an estimated
14,093 lbs of NMP was released to surface water from industrial sources. See Table_ApxD-l in
Appendix D for a TRI summary table and further details on recent releases of NMP to various
media.
2.3 Environmental Exposures
NMP may occur in \arious en\ ironmental media including sediment, soil, water and air. As part
of the NMP Problem Formulation (: >-PA 7( ;EPA completed a preliminary analysis of
environmental exposures for aquatic terrestrial species to NMP in these environmental media.
No additional information has been received or otherwise identified by EPA that would alter the
conclusions presented in the NMP Problem Formulation ( EPA. 2018c). EPA concluded that
no further analysis of en\ ironmental release pathways for environmental receptors is necessary
based on a qualitative assessment of the physical chemistry and fate properties of NMP and the
levels of \ \l P exposure that may be expected for organisms that inhabit these environmental
compartments
The evaluation of environmental exposures from the NMP Problem Formulation (U.S. EPA.
2018c) is summarized in the following subsections on potential presence in biological tissues
(biota), and possible exposures for aquatic and terrestrial receptors. The information is provided
for clarity in this RE and the conclusions remain unchanged from the NMP Problem Formulation
(U.S. EPA. 2018c).
2.3.1 Presence in the Environment and Biota
NMP exhibits low potential for bioaccumulation and bioconcentration in the environment.
Based on the estimated BAF and BCF values (0.9 and 3.16, respectively) (see Table 2-1), NMP
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is not expected to bioaccumulate or bioconcentrate in aquatic organisms (U.S. EPA. 2012c;
OECD. i v , ^ , g).
2.3.2 Aquatic Environmental Exposures
EPA used data from EPA's Toxics Release Inventory (TRI) and EPA's Exposure and Fate
Assessment Screening Tool, Version 2014 (E-FAST 2014;) to estimate the concentrations of
NMP released to surface water near discharging facilities. This exposure assessment for NMP is
considered a screening level analyses as it estimates conservative (higher end) surface water
concentrations. The assessment was conducted using data for the top 12 releasers reporting to the
TRI. Surface water concentrations were estimated based on the 2015 TRI data and EPA's E-E-
FAST, Version 2014 (E-FAST 2014). This exposure analysis is included in Appendix D of this
RE and is also the same as that performed in the NMP Problem Formulation (U.S. EPA. 2018c).
Using the 2015 TRI data and EPA's first-tier, Probabilistic Dilution Model (IMA I) within E-
FAST, facilities reporting the largest releases of NMP, surface water concentrations of NMP
were modeled based on the assumption of 12 or 250 days of release. The 12-day release scenario
represents an acute exposure scenario (wherein periodic maintenance and cleaning activities
could result in monthly releases). The 250-day release scenario represents a chronic exposure
scenario (wherein standard operations may result in continuous discharges of NMP) (see
Appendix D). The "high-end" surface water concentrations (i e . obtained assuming a low stream
flow for the receiving water body) ranged from 224 |ig/L for the maximum acute scenario (fewer
than 20 days of environmental releases per year) to 1.496 jug/I. lor the maximum chronic
exposure scenario (more than 20 days of en\ ironmental releases per year), respectively. These
predicted acute and surface water concentrations are compared to the Concentrations of Concern
identified for aquatic organisms in Section 3 I for I ji\ ironmental I lazards (Effects) to estimate
Environmental Risk in Section 4 I
2.4 Human Exposures
EPA evaluated acute and chronic exposures to workers and occupational non-users and acute
exposures to consumers by dermal contact with liquids, vapor-through-skin, and inhalation
routes in association with NMP use in industrial, commercial, and consumer applications. EPA
assessed these exposures by inputting exposure parameters into a physiologically based
pharmacokinetic (PlJPk) model, which is described in Appendix I.
The conditions of use to be assessed were described in Table 1-6. Due to expected similarities in
or the lack of data to distinguish between exposure scenarios for different conditions of use,
occupational exposures or consumer exposures for several of the subcategories of use in Table
1-6 were grouped and assessed together during risk evaluation. For example, formulation of
paints, coatings. adhesi\ es and sealants may generally have similar worker activities, and EPA
does not have data to distinguish whether workers are differently exposed for these different
formulations. Therefore, EPA has grouped these formulating conditions of use into one
occupational exposure scenario group (Incorporation into Formulation, Mixture, or Reaction
Product). Occupational groupings and consumer groupings are assessed separately. A crosswalk
of the conditions of use listed in Table 1-6 with the occupational and consumer exposure
scenarios assessed in this report is provided in Table 2-2. EPA assessed 26 occupational and
consumer exposure scenarios and applied them to 52 conditions of use.
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1063 Table 2-2. Crosswalk of Conditions of Use to Occupational and Consumer Scenarios
1064 Assessed in the Risk Evaluation
l.ile Cycle
Stage
Category "
Subcategory h
Occupational
Kxposurc Scenario
Consumer
Kxposurc
Scenario
Manufacture
Domestic
Manufacture
Domestic Manufacture
Section 2.4.1.2.1 -
Manufacturing
N/A
Import
Import
Section 2.4.1.2.2 -
Repackaging
N/A
Processing
Processing as
a reactant or
intermediate
Intermediate in Plastic
Material and Resin
Manufacturing and i n
Pharmaceutical and
Medicine Manufacturing
Section 2 4 12 3-
Chemical
Processing,
Excluding
lormulation
\ A
Other
Incorporated
inlo
formulation,
mixture or
reaction
product
Adhesives and sealant
chemicals in Adhesive
Manufacturing
Section 2.4.1.2.4 -
Incorporation into
Formulation,
Mixture, or Reaction
Product
N/A
Anti-adhesi\ e agents in
Printing and Related
Support Activities
Paint additives and coating
additives not described by
other codes in Paint and
Coating Manufacturing; and
Print Ink Manufacturing
Processing aids not
otherwise listed in Plastic
Material and Resin
Manufacturing
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Manufacturing; Primary
Metal Manufacturing; Soap,
Cleaning Compound and
Toilet Preparation
Manufacturing;
Transportation Equipment
Manufacturing; All Other
Chemical Product and
Preparation Manufacturing.
Printing and Related
Support Activities;
Services; Wholesale and
Retail Trade
Surface active agents in
Soap, Cleaning Compound
and Toilet Preparation
Manufacturing
Processing
Incorporated
into
formulation,
mixture or
reaction
product
Plating agents and surface
treating agents in Fabricated
Metal Product
Manufacturing
Section 2.4.1.2.4 -
Incorporation into
Formulation,
Mixture, or Reaction
Product
N/A
Solvents (which become
part of product formulation
or mixture) in Electrical
Equipment, Appliance and
('0111 ponent Manufacturing;
Other Manufacturing; Paint
and Coating Manufacturing;
Print Tnk Manufacturing;
Soap. Cleaning Compound
and Toilet Preparation
Manufacturing;
Transportation Equipment
Manufacturing; All Other
Chemical Product and
Preparation Manufacturing;
Printing and Related
Support Activities;
Wholesale and Retail Trade
Other uses in Oil and Gas
Drilling, Extraction and
Support Activities; Plastic
Material and Resin
Manufacturing; Services
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Lubricants and lubricant
additives in Machinery
Manufacturing
Section 2.4.1.2.5 -
Metal Finishing
N/A
Incorporated
into article
Paint additives and coating
additives not described by
other codes in
Transportation Equipment
Manufacturing
Section 2.4.1.2.5 -
Application of
Paints, Coatings,
Adhesives. and
Sealants
N/A
Solvents (which become
part of product formulation
or mixture), including in
Textiles, Apparel and
Leather Manufacturing
Section 2.4.1.2.4 -
Incorporation into
Formulation.
Mixture, or Reaction
Product
N/A
Processing
Incorporated
into article
Other, including in Plastic
Product Manufacturing
Section 2.4.1.2.3 -
Chemical
Processing,
1-a eluding
Formulation
\.\
Recycling
Recycling
Section 2.4.1.2.16-
Recycling and
Disposal
N/A
Repackaging
W holesale and Retail Trade
Section 2.4.1.2.2-
Repackaging
N/A
Distribution
in commerce
Distribution
Distribution in commerce
Activities related to
distribution (e.g.,
loading, unloading)
are considered
throughout the life
cycle rather than
using a single
distribution scenario,
so are not separately
assessed.
N/A
Industrial,
commercial,
and consumer
use
Paints and
Paint and coating removers
Section 2.4.1.2.6 -
Removal of Paints,
Section
2.4.2-
Paint
Removers
coatings
Adhesive removers
Coatings, Adhesives,
and Sealants
Section
2.4.2-
Adhesive
Removers
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Lacquers, stains, varnishes,
primers and floor finishes
Section 2.4.1.2.7 -
Application of
Paints, Coatings,
Adheshes. and
Sealants
Section
2.4.2-
Stains,
Varnishes
Powder coatings (surface
preparation)
N/A
Paint additives
and coating
additives not
described by
other codes
Use in Computer and
Electronic Product
Manufacturing,
Construction, Fabricated
Metal Product
Manufacturing, Machinery
Manufacturing, Other
Manufacturing, Paint and
Coating Manufacturing.
Primary Metal
Manufacturing,
Transportation Equipment
Manufacturing. Wholesale
and Retail Trade
Section
2.4.2-
Paint
Section
2.4.2 - Arts
and Crafts
Solvents (for
cleaning or
degreasing)
Use in Electrical
Equipment, Appliance and
Component Manufacturing.
Section 2.4.1.2.8 -
Electronic Parts
Manufacturing
N/A
Ink. loner, and
colorant
products
Printer ink
Section 2.4.1.2.9 -
Printing and Writing
N/A
Inks in writing equipment
N/A
Processing
aids, specific
to petroleum
production
Petrochemical
Manufacturing
Section 2.4.1.2.3 -
Chemical
Processing,
Excluding
Formulation
N/A
Industrial,
commercial,
and consumer
use
Adhesives and
sealants
Adhesives and sealant
chemicals including binding
agents
Section 2.4.1.2.5 -
Application of
Paints, Coatings,
Adhesives, and
Sealants
N/A
Single component glues and
adhesives, including
lubricant adhesives
Section
2.4.2-
Adhesives
Two-component glues and
adhesives, including some
resins
Section
2.4.2-
Sealants
Soldering materials
Section 2.4.1.2.10 -
Soldering
N/A
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Anti-freeze and de-icing
products
N/A
Automotive care products
Section 2.4.1.2.11 -
Commercial
Aulomoli\ e Serving
Section
2.4.2 - Auto
Interior
Cleaner
Auto
Interior
Spray
Cleaner
Lubricants and greases
N/A
Metal products not
covered elsewhere
Section 2.4 12 5-
Metal Finishing
N/A
Laboratory chemicals
Section 2.4.1.2.12-
I.aboratory Use
N/A
Lithium ion batteries c
\ A
N/A
Other uses
Cleaning and luiniluic care
products, including wood
cleaners, gasket ienio\ei s
Section 2.4.1.2.13 -
Cleaning
Section
2.4.2-
Cleaners/
Degreasers
Engine
Cleaner/
Degreaser
Oilier uses in Oil and Gas
Drilling. l-\liaclion and
Support Acti\ ilies
Section 2.4.1.2.3 -
Chemical
Processing,
Excluding
Formulation
N/A
Lubricant and lubricant
additives, including
hydrophilic coatings
Section 2.4.1.2.5 -
Metal Finishing
Section
2.4.2-
Spray
Lubricant
Fertilizer and other
agricultural chemical
manufacturing - processing
aids and solvents
Section 2.4.1.2.14 -
Fertilizer
Application
N/A
Pharmaceutical and
Medicine Manufacturing -
functional fluids (closed
systems)
Section 2.4.1.2.3 -
Chemical
Processing,
Excluding
Formulation
N/A
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Wood preservatives
Section 2.4.1.2.15 -
Wood Preservatives
N/A
Disposal
Disposal
Industrial pre-treatment
Section 2 4 1 2 16 -
Rccvclinu and
1 )i sposal
N/A
Industrial wastewater
treatment
N/A
Publicly owned treatment
works (POTW)
N/A
Underground injection
N/A
Landfill (municipal,
hazardous or other land
disposal)
N/A
Incinerators (municipal and
hazardous waste)
N/A
Emissions to air
N/A
a These categories of conditions of use appear in the Life Cycle Diauram. ivl'kvl CDR codes, and broadly represent
conditions of use of NMP in industrial and/or commercial sellings,.
bThese subcategories reflect more specific uses ol WIP
0 This condition of use applies to manufacture and processing
N/A means these conditions of use are not applicable In occupational or consumer exposures
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2.4.1 Occupational Exposures
For the purpose of this assessment, EPA considered occupational exposure of the total workforce of
exposed users and non-users, which include but are not limited to male and female workers of
reproductive age who are >16 years of age. Female workers of reproductive age are >16 to less than 50
years old. Adolescents (>16 to <21 years old) are a small part of this total workforce. The occupational
exposure assessment is applicable to and covers the entire workforce who are exposed to NMP.
EPA evaluated acute and chronic exposures to workers and occupational non-users (ONUs) associated
with dermal contact with liquids (workers only), vapor-through-skin, and inhalation routes in association
with NMP use in industrial and commercial applications, which are shown in Table 2-2. Oral exposure
via incidental ingestion of inhaled vapor/mist/dust will be considered as an inhalation exposure as noted
in Figure 1-2 because EPA does not have data or methods to fractionate the total NMP inhaled into the
amount of NMP that deposits in the upper respiratory system and the amount of NMP that goes into the
lung.
EPA assessed these exposures by inputting exposure parameters into a physiologically based
pharmacokinetic (PBPK) model, which is described in Appendix I Parameter development for each
occupational exposure scenario assessed is described in Section 2 4 11. More detailed information about
the parameter development may be found in the supplemental document Risk Evaluation for N-
Methylpyrrolidone (2-Pyrrolidinone, 1 Methyl-) tSMP). Supplemental Information on Occupational
Exposure Assessment (U.S. EPA. 2019r).
For each scenario, EPA distinguishes between exposures to workers and ONUs when possible. A
primary difference between workers and ONUs is that workers may have direct dermal contact with
liquid chemicals that they handle, u hereas ONUs located in the general vicinity of workers do not have
direct dermal contact with liquids handled by the workers. Examples of ONUs include supervisors,
managers, and other employees that may he in the production areas but do not perform tasks that result
in direct dermal contact with liquids. I-PA expects that ONUs are exposed to lower air concentrations
than workers since they may be luriher from the emission source than workers. When EPA cannot
distinguish ONU exposures from workers. EPA assumes ONUs are exposed to lower air concentrations
as compared to workers
2.4.1.1 Occupational Kxposures Approach and Methodology
This section summarizes the occupational dermal and inhalation exposure parameters and concentrations
for NMP in the \ arious industries and scenarios shown in Table 2-2. These parameters were used as
PBPK model inputs for the risk evaluation. The supplemental document, Risk Evaluation for N-
Methylpyrrolidone (2-J'yrro/idinone, 1 Methyl-) (NMP), Supplemental Information on Occupational
Exposure Assessment ( 2019r) provides background details on industries that may use NMP,
worker activities, processes, numbers of sites and numbers of potentially exposed workers. This
supplemental document also provides detailed discussion on the values used for the dermal exposure
parameters and air concentrations and associated worker inhalation parameters presented in this section.
Key Parameters for PBPK Modeling
To derive internal exposure estimates for acute and chronic occupational exposures, the PBPK model
required a set of input parameters related to exposures by the dermal and inhalation routes:
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• NMP weight fraction in the liquid product;
Total skin surface area of hands in contact with the liquid product;
Glove protection factor (if applicable);
Duration of dermal contact with the liquid product;
Air concentration for inhalation and vapor-through-skin exposure; and
Body weight of the exposed worker.
EPA assumed that the skin of the hands was exposed dermally to NMP at the specified liquid weight
fraction and skin surface area and that there was simultaneous exposure by inhalation and vapor-
through-skin absorption for unobstructed skin areas. As described below, air concentrations were
adjusted to duration of contact of liquid on the skin, which is assumed to be removed by cleaning at the
end of the work period. Acute scenarios assumed 1 day of exposure and chronic scenarios assumed 5
days of exposure per week.
EPA used literature sources for estimating many of these occupational exposure parameters F.PA used
modeling or generic assumptions when data were not a\ ailahlc
For most PBPK input parameters, EPA did not find enough data to determine statistical distributions of
the actual exposure parameters and concentrations. Within the disirihulions, central tendencies describe
50th percentile or the substitute that most closely represents the 50lh percentile. The high-end of a
distribution describes the range of the distribution above 90th percentile (; EPA. 1992). Ideally, EPA
would use the 50th and 95th percentiles for each parameter Where these statistics were unknown, the
mean or mid-range (mean is preferable to mid-range) sei \ ed as substitutes for 50th percentile and the
high-end of ranges served as a substitute for 95th percentile. However, these substitutes were uncertain
and not ideal substitutes for the percentiles. EPA could not determine whether these substitutes were
suitable to represent statistical distributions of real-world scenarios.
EPA selected grouped sets of indi\ idual input parameter values intended to represent central tendency
and high-end occupational exposure scenarios To generate each central tendency scenario result, EPA
used a group of all central tendency input parameter values relevant to the scenario. To generate each
high-end scenario result. I-PA used a group of mostly high-end input parameter values relevant to the
scenario except body weight, u hich is a median value. Using mostly high-end input values is a plausible
approach to estimate a high-end PliPk result for the periods of acute and chronic exposures of 1 to 5
days.
Weight Fraction
To support this risk e\ aluation. I-PA determined the weight fraction of NMP in various products through
information provided in the a\ ailable literature, previous risk assessments and the 2017 NMP Market
Profile (Abt. 2017). This Market Profile was prepared in part by searching Safety Data Sheets (SDSs) of
products that contain NMP and compiling the associated name, use, vendor and NMP concentration
associated with each of these products. Where a data point was provided as range of NMP
concentrations for a certain product (e.g., paints and coatings), EPA utilized the mid-range (middle) and
high-end (maximum) weight fractions to estimate potential exposures. Where multiple data points for a
given type of product (e.g., paints and coatings) were available, EPA estimated exposures using the
central tendency (50th percentile) and high-end (95th percentile) NMP concentrations.
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Skin Surface Area
For both consumer and occupational user dermal exposure for liquid contact, EPA used skin surface area
values both for the hands of females and for the hands of males, obtained from the 2011 edition of
EPA's Exposure Factors Handbook (Table 7-13) ( ). These values overestimate
exposures for younger members of the workforce whose hand surface areas would be smaller. One
exception is for the OES that includes Writing, 1 cm2 was assumed based on a literature estimate for
writing inks (NICNAS. 2016). For the remainder of the occupational dermal exposure assessment, EPA
used the following values:
• high-end value, which represents two full hands in contact with a liquid: 890 cm2 (female),1070
cm2 (males)
• central tendency value, which is half of two full hands (equi\ alent lo oik- full hand) in contact
with a liquid and represents only the palm-side of both hands exposed lo a liquid: 445 cm2
(females), 535 (males)
Occupational non-users (ONUs) are not expected to ha\ e direct contact with NMP-based liquid products
unless an incident (e.g., spill) were to occur. However, PIJPK modeling of ONU (no liquid contact) used
a skin surface area value of 0.1 cm2 (about 0.1% of values used lor occupational users) for liquid
exposure to prevent a division by zero error in model equations.
For dermal exposure to vapor for both occupational users and ONLs, the PBPK modeled up to 25% of
the total skin surface area, corresponding to the lace. neck, arms and hands, as exposed to and capable of
absorbing vapors, minus any area covered by personal protection equipment (PPE). This area, which is
programmed into the PBPK model, is not a variable input \ alue
Glove Usage
EPA also made assumptions about glove use and associated protection factors (PFs). Where workers
wear gloves, workers are exposed to \ MP-based product that penetrates the gloves, including potential
seepage through the cuff from improper donning of the gloves, permeation of NMP through the glove
material, and the gloves may occlude the e\ aporation of NMP from the skin. Where workers do not
wear glo\es. workers are exposed through direct contact with NMP.
Overall. \ .P \ understands that workers may potentially wear gloves but does not know the likelihood
that workers w ear gloves of the proper type and have training on the proper usage of gloves. Some
sources indicate that workers wear chemical-resistant gloves (Meier et ai. 201 \ » >< ^ M J'09a;
NICNAS „., j:), while others indicate that workers likely wear gloves that are more permeable than
chemical-resistant g1o\ es ( i 1 • 2013). No information on employee training was found. Data on the
prevalence of glo\ e use is not available for most uses of NMP. One anecdotal survey of glove usage
among workers performing graffiti removal indicates that 87% of workers wear gloves, although the
glove materials varied and were sometimes not protective; only a small fraction of these workers used
gloves made of optimal material for protection against NMP and some used cloth or leather gloves
(Anufidt et ai. 2000). Prior to the initiation of this risk evaluation EPA had gathered information in
support of understanding glove use for handling pure NMP and for paint and coatings removal using
NMP formulations. This information may be generally useful for a broader range of uses of NMP and is
presented for illustrative purposes in 6E.1.1. SDSs found by EPA recommend glove use (see Appendix
E.1.2). Initial literature review suggests that there is unlikely to be enough data to justify a specific
probability distribution for effective glove use for a chemical or industry. Instead, the impact of effective
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glove use is explored by considering different protection factors, which are further discussed below and
compiled in Table 2-3.
Gloves only offer barrier protection until the chemical breaks through the glove material. Using a
conceptual model, Cherrie et al. (2004) proposed a glove workplace PF - the ratio of estimated uptake
through the hands without gloves to the estimated uptake through the hands while wearing gloves: this
protection factor is driven by glove usage practices and by flux, which varies with time. The ECETOC
TRA v3 model represents the protection factor of gloves as a fixed, assigned protection factor equal to 1,
5, 10, or 20 (Marquart et al.. 2017). When assuming glove use, EPA assumed protection factors using
this strategy. Given the limited state of knowledge about the protection afforded by gloves in the
workplace, it is reasonable to utilize the PF values of the ECETOC TRA \ 3 model (Marquart et al..
2017). rather than attempt to derive new values.
For each occupational exposure scenario, EPA used professional judgment to predict the likelihood of
the use of gloves based on the characteristics described in Table 2-3, and the associated PFs are
presented as what-if scenarios. For OESs with only industrial sites, EPA assumes that workers are likely
to wear protective gloves and have basic training on the proper usage of these gloves, corresponding to a
protection factor of 10 for both the central tendency and high-end exposure scenarios. In high-end
scenarios that include both commercial and industrial sites, EPA assumes that either no gloves are used
or, if gloves are used, that glove material may not be protective, each of u liich corresponds to a
protection factor of 1. This assumption is based on the survey of graffiti removers noted that only a
small fraction of these workers used gloves made of optimal material lor protection against NMP and
some used cloth or leather gloves (Anundi et ; L ) I or these same scenarios, EPA assesses a
central tendency scenario assuming the use of gloves with minimal to no employee training,
corresponding to a prokvtion factor of 5 As indicated in Table 2-3, use of protection factors above 1 is
valid only for glove materials that ha\ e been tested for permeation against the NMP-containing liquids
associated with the condition of use I -PA has not found information that would indicate specific activity
training (e.g., procedure for glove remo\ al and disposal) for tasks where dermal exposure can be
expected to occur in a majority of sites in industrial only OESs, so the PF of 20 is not assumed for any
central tendency or high-end estimates but would he applicable to lower percentile (below central
tendency) exposure estimates Additional explanations of the selection of PFs for each exposure scenario
and of occlusion are included in the supplemental document Risk Evaluation for N-Methylpyrrolidone
(2-Pyrrol ii In tone, 1 Methyl-) (SMI'), Supplemental Information on Occupational Exposure Assessment
(I :)•
In addition to the assumed central tendency and high-end scenarios, EPA conducted additional modeling
of exposures for the lull range of glove use or no glove use to determine impacts on exposures and
MOEs as what-if scenarios The results of this additional modeling are shown in Section 4.2.2.
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Table 2-3. Glove Protection Factors for Different Dermal Protection Strategies from ECETOC
I R A v3
Dermal Protection Characteristics
Setting
Protection
Kactor. PI-"
a. No gloves used, or any glove / gauntlet without permeation data
and without employee training
1
b. Gloves with available permeation data indicating that the
material of construction offers good protection for the substance
Industrial and
Commercial Uses
5
c. Chemically resistant gloves (i.e., as b above) with "basic"
employee training
10
d. Chemically resistant gloves in combination with specific activity
training (e.g., procedure for glove removal and disposal) for tasks
where dermal exposure can be expected to occur
Industrial I ses
Only
20
Duration of Dermal Contact
Where available, EPA utilized exposure durations from the a\ ail able task-based inhalation monitoring
data. No dermal duration data were found. In lieu of dermal duration data or task-based durations from
inhalation monitoring data, EPA assumed a minimum duration of 1 hour/day, which is a reasonable
assumption considering the initial contact 1ime with the formulation containing NMP plus the time after
direct contact when the thin film evaporates lYom and absorbs into the skin. EPA assumed a high-end
value of 8 hours/day (i.e., a full shift). As a central tendency estimate, EPA assumed a mid-range value
of 4 hours/day (the calculated mid-point of 4.5 was rounded to 4 hours/day). The low-end and high-end
values are consistent with EPA's documented standard model assumptions for occupational dermal
exposure modeling (U.S. EPA )
Air Concentration for Inhalation ami I apor-ihrouzh-Skin Exposure
EPA reviewed workplace inhalation monitoring data collected by government agencies such as OSHA
and NIOSH, and monitoring data found in published literature (i.e., personal exposure monitoring data
and area monitoring data). Data were e\ aluated using the evaluation strategies laid out in the Application
of Systematic Review hi I SiI Risk Eva Inations (U.S. EPA. 2018a). and the evaluation details are shown
in two supplemental files: Risk I .valuation for N-Methylpyrrolidone (NMP), Systematic Review
Supplemental lile: Data Quality Evaluation for Occupational Exposure and Release Data (U.S. EPA.
2019p) and Risk I .valuation for N-Methylpyrrolidone (2-Pyrrolidinone, 1-Methyl-) Systematic Review
Supplemental lute: / kita Quality Evaluation of Environmental Releases and Occupational Exposure
Common Sources ( SPA, 2019o). Where available, EPA used air concentration data and estimates
found in government or published literature sources to serve as inputs to the PBPK modeling for
occupational exposures to NMP. There is not a known correlation between weight fraction of NMP in
the material being handled / used and the concentration of NMP in air. Where air concentration data
were not available, modeling estimates were used. Details on which models EPA used are included in
Section 2.4.1.2 for the applicable OESs and discussion of the uncertainties associated with these models
is included in Section 2.4.1.4.
EPA evaluated personal monitoring data or modeled near-field exposure concentrations potential
inhalation and vapor-through-skin exposures for workers. Since ONUs do not directly handle NMP,
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EPA reviewed personal monitoring data, modeled far-field exposure concentrations, and area
monitoring data in evaluating potential inhalation and vapor-through-skin exposures for ONUs. Because
modeled results are typically intended to capture exposures in the near-field, modeling that does not
contain a specific far-field component are not considered to be suitable for ONUs. Area monitoring data
may potentially represent ONU exposures depending on the monitor placement and the intended sample
population. Inhalation data sources did not usually indicate whether NMP exposure concentrations were
for occupational users or occupational non-users (ONUs). For inhalation and vapor-through-skin
exposures, if EPA cannot distinguish ONU exposures from workers, EPA assumes that ONUs
experience lower air concentrations compared to workers.
For PBPK modeling, the duration of inhalation exposure must equal the duration of dermal exposure.
Therefore, where EPA did not have exposure durations from task-based monitoring data, EPA adjusted
air concentrations by multiplying by a ratio of duration of the air concentration a\ ci aging time to
duration of dermal exposure to liquid, which is discussed above.
Few literature sources indicate the use of respirators for reducing worker exposures to NMP hv
inhalation. Therefore, EPA central tendency and high-end scenarios do not incorporate protection factors
for respirator use. Regarding respirator use, only one of the NM P studies containing worker inhalation
data specified the type of respirator used by the workers in the study This respirator, a half mask air-
purifying respirator with organic vapor cartridges ( eft J, is classified as having an assigned
protection factor (APF) of 10. Therefore, EPA conducted additional modeling representing scenarios
below central tendency for the use of respirators pro\ idinu an APF of I" This modeling reduces
inhalation concentrations by a factor of 10 as intended u hen this type of respirator is used in accordance
with OSHA's Respiratory Protection standard (29 OR. 1910.134) While respirators with other APFs
may be used, EPA only included this API' in additional modeling The results of this additional
modeling are shown in Section 4 2 2
Body Weight
Both the consumer and occupational dermal exposure assessments used the 50th percentile body weights
for pregnant women in their lust trimester, which is 74 kg, and for males, which is 88 kg, for both
central tendency and high-end exposure scenarios. EPA obtained these values from the 2011 edition of
EPA's Exposure Factors I landhook (Table 8-29) (U.S. EPA. 20111
2.4.1.2 Occupational lixposure Scenarios
Details of the data, modeling, and associated exposure-related information for each of the Occupational
Exposure Scenarios (OES) listed in Table 2-2 and in the subsections below are available in the
supplemental document Risk Evaluation for N-Methylpyrrolidone (2-Pyrrolidinone, 1 Methyl-) (NMP),
Supplemental Information on Occupational Exposure Assessment. (U.S. EPA. 2019r)
The following subsections contain a summary of dermal and inhalation parameter estimates for each
OES. Information on the number of potentially exposed workers and occupational non-users (ONUs)
can be found in Table 2-4. Details on the parameter estimates as well as process descriptions, numbers
of sites and potentially exposed workers, and worker activities for each OES are available in the
supplemental document ( 019r). A summary set of all central tendency and high-end
scenarios parameter inputs to the PBPK model is shown in Table 2-66.
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Key uncertainties toward exposure estimates are summarized in Section 2.4.1.4.
EPA estimated numbers of workers in the assessed industries. Where available, EPA used CDR data to
provide a basis to estimate the numbers of sites, workers, and occupational non-users (ONUs). EPA
supplemented the available CDR data with U.S. economic data using the following method:
1. Identify the North American Industry Classification System (NAICS) codes for the industry
sectors associated with these uses.
2. Estimate total employment by industry/occupation combination using the Bureau of Labor
Statistics' (BLS) Occupational Employment Statistics (OES) data ( ri v 2016).
3. Refine the OES estimates where they are not sufficiently granular In using the U.S. Census'
Statistics of US Businesses (SUSB) (citation) data on total employ ment In 6-digit NAICS.
4. Use market penetration data to estimate the percentage of employees likely lo be using NMP
instead of other chemicals.
5. Combine the data generated in Steps 1 through 4 lo produce an estimate of the number of
employees using NMP in each industry/occupation combination, and sum these lo arrive at a
total estimate of the number of employees with exposure.
Market penetration data for NMP are not readily available at this lime, therefore, site, worker, and ONU
estimates do not take this into account and likely overestimate the number of sites, workers, and ONUs
potentially exposed to NMP. Where end-use sector is not clear, relevant GSs and ESDs are used to
estimate the number of sites and workers, such as for metal finishing.
Estimated numbers of occupational workers in the assessed industries are shown in Table 2-4. The
number of workers exposed to NMP lor these industries is not known. Additionally, the proportion of
workers that are exposed in an industrial \ ersus commercial setting is unknown. Details of these
estimates may be found in the supplemental document Risk Evaluation for N-Methylpyrrolidone (2-
Pyrrolidinone, 1 Methyl-) iSMI'). Siipplcmciiial Information on Occupational Exposure Assessment
(U.S. EPA. 2019rY
Table 2-4. Kslimaled Numbers of Workers in the Assessed Industry Uses of NMP a
Occupational Kxposurc Scenario
Number of W orkers h
Manufacturing
2,800 '
Repackaging
1,100 c
Chemical Processing, Excluding I'ormulation
5,400 c
Incorporation into Formulation, Mixture, or Reaction Product
1,900 c
Application of Paints, Coatings, Adhesives and Sealants
2,000,000
Printing and Writing
53,000
Metal Finishing
530,000
Removal of Paints, Coatings, Adhesives and Sealants
410,000
Cleaning
190,000
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Commercial Automotive Servicing
910,000
Laboratory Use
420,000
Electronic Parts Manufacturing
660,000
Soldering
4,000,000
Fertilizer Application
1,300,000
Wood Preservatives
380,000
Recycling and Disposal
200 c
a The number of worker estimates are based on industry-specific data that arc iiidcpciidciil nf WIP usaee and the
portion of workers that are exposed to NMP within these industries is unknown.
b These numbers are rounded to two significant figures.
0 The number of sites associated with these occupational exposure scenarios were determined from ( 1 )k or TRI
data. However, the number of workers that are exposed to NMP ai I hose sites is unknown.
2.4.1.2.1 Manufacturing
For this industrial exposure scenario, EPA assessed inhalation, vapor-ill rough-skin, and dermal
exposures from the loading of various containers (i e, drums, tank trucks, rail cars) with pure NMP.
While EPA does expect that workers may perform additional activities din ing this scenario, such as
sampling or maintenance work, EPA expects that loading acti\ ities present the largest range of potential
exposures.
Inhalation and Vapor-throunh-SUin
EPA found no monitoring data specific to the manufacture of NMP. However, there is a German source
with monitoring data for the storing and conveying of pure NMP, which may occur during
manufacturing ( ) These data do not include additional details such as the industry, associated
worker activities, type of storing and com eying systems, and sampling time, resulting in a data quality
rating of medium. EPA modeling estimates had higher quality rating, so EPA did not use this German
monitoring data. EPA also found a source of European modeling estimates for the manufacturing of
NMP ( 1 ). This modeled data had a medium data quality rating and EPA modeling estimates
had higher data quality, so EPA did not use the European modeling data. Due to limited relevance and
quality of (ierman monitoring data and European modeling estimates found in the published literature,
EPA used modeling estimates of air concentrations with the highest data quality for this use. EPA's
modeled exposure concentrations are similar in value and the same order of magnitude as the European
modeling estimates. EPA's Tank Truck and Railcar Loading and Unloading Release and Inhalation
Exposure Model invoh es deterministic modeling and the Drum Loading and Unloading Release, and
Inhalation Exposure Model involves probabilistic modeling.
The inhalation exposure concentrations modeled by EPA for loading of NMP are summarized into the
input parameters used for the PBPK modeling in Table 2-5. Note that the exposure duration for the
central tendency and high-end exposure scenarios for loading into drums are the same because the
unloading rate does not vary in that model. The supplemental document Risk Evaluation for N-
Methylpyrrolidone (2-Pyrrolidinone, 1 Methyl-) (NMP), Supplemental Information on Occupational
Exposure Assessment ( 2019r) provides additional details.
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Table 2-5. Summary of Parameters for PBPK Modeling of Worker Inhalation Exposure During
Manufacturing
Work
Activity
Parameter
Characterization
lull-Shift
NMP Air
Concentration
Duration-
liased NMP
Air
Concentration
Source
Data
Quality
Rating
(nig/nr\ 8-hr
TWA)
(nig/nr*)
lank Truck and
Loading
NMP into
bulk
containers
Central tendency
(50th percentile)
0.047
0.760 (duration
= 0.5 hr)
Railcar
I <>ading and
1 nloading
Release and
High-end (95th
percentile)
0.190
1 52 (duration
1 hr)
Inhalation
Exposure
Model flJ.S.
EPA. 2013a)
Not
applicable21
Loading
NMP into
Central tendency
(50th percentile)
0 427
1 05 (duration
2.06 hr)
Drum Loading
and Unloading
Release and
Inhalation
drums
High-end (95th
percentile)
1.51
5 S5 (duration
2 do hr)
l.xposure
Model (IJ.S.
;PA. 2.013 a)
11 - EPA models are standard sources used In IP V for occupational exposure assessments. EPA did not systematically review
models that were developed In IP \
Dermal
Table 2-6 summarizes the parameters used to assess dermal exposure during the manufacturing of NMP.
For this life cycle stage. I -PA assessed dermal exposures during the loading of pure NMP into bulk
containers and into drums Most of these parameters were determined based on assumptions described in
Section 2.4 I 1. EPA used data from 2d I (•> CDR and literature sources to determine the NMP weight
fraction These underlying data have data quality ratings of high. Because this scenario has only
industrial sites. I-PA assumes that workers are likely to wear protective gloves and have basic training
on the proper usage of these glo\ es for both central and high-end exposures, corresponding to a
protection factor of I
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Table 2-6. Summary of Parameters for Worker Dermal Exposure to Liquids During
Manufacturing
Work
Activity
Parameter
Characterization
(•love
Protection
l'"actor(s)
NMP
W eight
Kraction
Skin
Surface
Area
Kxposed "
Kxposurc
Duration
liody
W eight"
I n it less
cm2
lir/dav
IvSi
Loading
NMP into
bulk
containers
Central Tendency
10
1
445 (I')
535 (m)
i) 5
74 (f)
88 (m)
High-end
10
1
890 (I')
1,070 (m)
1
Loading
NMP into
drums
Central Tendency
10
1
445 (f)
535 (m)
2 1)0
74 (f)
88 (m)
High-end
10
1
890 (1)
1,070 (m)
2 do
1.EPA assessed these exposure factors for both females and malci. Values associated with females are denoted with (f) and
values associated with males are denoted with (m).
PBPK Inputs
EPA assessed PBPK parameters for central tendency and high-end exposure scenarios based on the
characterizations listed in Table 2-7.
The numeric parameters corresponding to the characterizations presented in Table 2-7 are summarized
in Table 2-8. These are the inputs used in the PBPK model.
Table 2-7. Characterization of PBPK Model Input Parameters for Manufacturing of NMP
Scenario
Work
Activity
Air
Concentration
Data
Characterization
Kxposurc
Duration
Skin
Surface
Area
Exposed
(•loves
NMP Weight
Kraction
Characterization
Central
Tendency
1 .oadinu of
bulk-
containers
Central tendency
(5Dlh percentile)
Duration
calculated
by model
1-hand
\ es
\ A - |DO"() is
assumed for both
exposure scenarios
High-end
Loading of
drums
1 liuh-end (95th
percentile)
Duration
calculated
by model
2-hand
Yes
N/A - 100% is
assumed for both
exposure scenarios
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Table 2-8. PBPK Model Input Parameters for Manufacturing of NMP
Skin Surface
Area
Kxposed
(cm2)
"'Scenario
Duralion-liascd
NMP Air
Concent ration
(ing/nr')
Kxposure
Duration
(I")
Skin
Surface
Area
Kxposed
(cm2)
(•loves
Protection
Kactor
NMP
\\ eight
Iraction
IJodv
Weight
(kg)"
Central
Tendency
0.760
0.5
445 (f)
535 (m)
ID
1
74 (f)
88 (m)
High-end
5.85
2.06
890 (f)
1,070 (m)
10
1
74 (f)
88 (m)
a EPA assessed these exposure factors for both females and males. Values associated with t annics are denoted with (f) and
values associated with males are denoted with (m).
bEPA assessed a skin surface area exposed to liquid NMP of 0.1 cm2 for ONUs for each scenario 1 low e\ er, EPA did not
assess glove usage (protection factor = 1) for ONUs.
Summary
In summary, dermal and inhalation exposures are expected lor this use LPA has not identified
additional uncertainties for this use beyond those included in Section 2 4 14. EPA identified primary
strengths and limitations and assigned an overall confidence to the occupational exposure scenario
inputs to the PBPK model, as discussed below I-PA considered the assessment approach, the quality of
the data, and uncertainties to determine the le\ el of confidence Note that the effects of the limitations
on this assessment are discussed in Section 2 4 14
Primary Strengths
EPA assessed dermal exposure to liquids using the most recent CDR data for concentration provided by
industry submitters. Modeling, in the middle of the approach hierarchy, was used to estimate
occupational air concent rat ions for both the loading of NMP into bulk containers and into drums. For
modeling of these air concentrations. I -PA attempted to address variability in input parameters by
estimating both central tendency and high-end parameter values. Additionally, for modeling of air
concentrations during the loading of drums, LP A used Monte Carlo simulation to capture variability in
input parameters. EP A expects the duration of inhalation and dermal exposure to be realistic for the
loading activities, as the durations are based on the length of time to load NMP into specific container
sizes (i e . tank trucks, rail cars, and drums).
Primary Lumiaiions
Due to lack of data. I7.P A has no method to determine the representativeness of the estimates of duration
of inhalation and dermal exposure for the loading activities toward the true distribution for all worker
activities. NMP concentration is reported to CDR as a range and EPA assessed only the upper end of the
range since a central value cannot be ascertained for this scenario. Skin surface areas for actual dermal
contact are uncertain. EPA did not find data on the use of gloves for this occupational exposure scenario
and assumed glove usage is likely based on professional judgment. The assumed glove protection factor
values are uncertain. EPA is uncertain of the accuracy of the emission factors used to estimate fugitive
NMP emissions and thereby to model NMP air concentrations. The representativeness of the modeling
results toward the true distribution of inhalation concentrations for this occupational exposure scenario
is uncertain.
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Overall Confidence
Considering the overall strengths and limitations, the overall confidence of the PBPK input parameters
for this occupational exposure scenario is medium.
2.4.1.2.2 Repackaging
For this industrial exposure scenario, EPA assessed inhalation, vapor-through-skin, and dermal
exposures from the unloading of various containers (i.e., drums, tank trucks, rail cars) containing pure
NMP. While EPA does expect that workers may perform additional activities during this scenario, such
as sampling or maintenance work, EPA expects that unloading activities present the largest range of
potential exposures.
Inhalation and Vayor-throush-Skin
Since no monitoring data or modeling estimates were found for Repackaging.
EPA determined the same monitoring data and modeled exposure estimates for manufacturing could be
applied to this occupational exposure scenario, due to the similarity in work acti\ ities (e u . loading
vessels) and corresponding NMP concentrations between the two occupational exposure scenarios. The
air concentration estimates from Section 2.4.1.2.1 for manufacturing are used for this occupational
exposure scenario.
Dermal
EPA compiled the same dermal exposure parameters lor this occupational exposure scenario as for
manufacturing. The dermal exposure parameters from Section 2 4 12 1 lor manufacturing are used for
this occupational exposure scenario.
PBPK Inputs
EPA assessed PBPK parameters for central tendency and high-end exposure scenarios based on the
characterizations listed in TaMe 2-1)
The numeric parameters corresponding to the characterizations presented in Table 2-9 are summarized
in TaMe 2-l<) These are the inputs used in the I'lJPk model.
Table 2-'). Characterization of I'KPIv Model Input Parameters for Repackaging
Scenario
Work
Activity
Air
Concentration
Data
Characterization
Kxposnrc
Duration
Skin
Surface
Area
Kx posed
(•loves
NMP Weight
l-'raction
Characterization
Central
Tendency
Unloading
bulk
containers
Central tendency
(50th percentile)
Duration
calculated
by model
1-hand
Yes
N/A - 100% is
assumed for both
exposure scenarios
High-end
Unloading
drums
High-end (95th
percentile)
Duration
calculated
by model
2-hand
Yes
100% is assumed
for both exposure
scenarios
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Table 2-10. PBPK Model Input Parameters for Repackaging
Scenario
Duration-
liased NMP
Air
Concentration
(nig/nr*)
Kxposurc
Duration
(In)
Skin Surface
Area Kxposed
(cm2)ilh
(•loves
Protection
Kactor
NMP
Weight
l-'raction
liodv Weight
(kg)"
Central
Tendency
0.760
0.5
445 (f)
535 (m)
10
1
74 (f)
88 (m)
High-end
5.85
2.06
890 (f)
1,070 (m)
ID
1
74 (f)
88 (m)
a EPA assessed these exposure factors for both females and males. Values associated \\ nli females are denoted with (f) and
values associated with males are denoted with (m).
bEPA assessed a skin surface area exposed to liquid NMP of 0.1 cm fur ()\t Is for each scenario 1 lowever, EPA did not
assess glove usage (protection factor = 1) for ONUs.
Scenario
Duration-
liased NMP
Air
Concentration
(nig/nr')
Kxposurc
Duration
(In)
lull-Shift
NMP Air
Concentration
(ni!>/nr<. 8-hr
TWA)"
Skin
Surface
Area
Kxposed
(cm2) h
(•loves
Protection
l-'actor
NMP Weight
l-'raction
Central
Tendency
0.76
0.5
0 0475
445 (f)
535 (m)
10
1
High-end
5.85
2.06
1.51
S^n (f)
I.070 (m)
10
1
a Calculated based on the duration-based air concentration and exposure dilution. 8-hour TWA = (Duration-based air
concentration) x (Exposure diiiation)/8 hours
b EPA assessed these exposure factors fur hoi li females and males. Values associated with females are denoted with (f) and
values associated with males are denoted w ii li i in i
Summary
In summary, dermal and inhalation exposures are expected for this use. EPA has not identified
additional uncertainties lor this use beyond those included in Section 2.4.1.4. EPA identified primary
strengths and limitations and assigned an overall confidence to the occupational exposure scenario
inputs to the PBPK model, as discussed below. EPA considered the assessment approach, the quality of
the data, and uncertainties to determine the level of confidence. Note that the effects of the limitations
on this assessment are discussed in Section 2.4.1.4.
Primary Strengths
EPA assessed dermal exposure to liquids using the most recent CDR data for concentration provided by
industry submitters. Modeling, in the middle of the approach hierarchy, was used to estimate
occupational inhalation exposure concentrations for both the unloading of NMP from bulk containers
and from drums. For modeling of these air concentrations, EPA attempted to address variability in input
parameters by estimating both central tendency and high-end parameter values. Additionally, for
modeling of air concentrations during the loading of drums, EPA used Monte Carlo simulation to
capture variability in input parameters. EPA expects the duration of inhalation and dermal exposure to
be realistic, as the durations are based on the length of time to load NMP into specific container sizes
(i.e., tank trucks, rail cars, and drums).
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Primary Limitations
The representativeness of the estimates of duration of inhalation and dermal exposure for the unloading
activities toward the true distribution of duration for all worker activities in this occupational exposure
scenario is uncertain. NMP concentration is reported to CDR as a range and EPA assessed only the
upper end of the range since a central value cannot be ascertained for this scenario. Skin surface areas
for actual dermal contact are uncertain. EPA did not find data on the use of gloves for this occupational
exposure scenario and assumed glove usage is likely based on professional judgment. The assumed
glove protection factor values are uncertain. EPA is uncertain of the accuracy of the emission factors
used to estimate fugitive NMP emissions and thereby to model NMP air concentrations. The
representativeness of the modeling results toward the true distribution of inhalation concentrations for
this occupational exposure scenario is uncertain.
Overall Confidence
Considering the overall strengths and limitations, the o\ era! I confidence of the PlJI'k input parameters
for this occupational exposure scenario is medium.
2.4.1.2.3 Chemical Processing, Excluding Formulation
This scenario includes the use of NMP for processing activities other than formulation (i.e., non-
incorporative processing). Specifically, this may include the use of NMP as an intermediate, as a media
for synthesis, extractions, and purifications, or as some other type of processing aid. EPA identified the
following industries that use NMP in this manner ( VM °0_13); ( ):
• Agricultural chemical manufacturing
• Petrochemical manufacturing
• Pharmaceutical manufacturing
• Polymer product manufacturing
For this industrial exposure scenario. N\\ assessed inhalation, vapor-through-skin, and dermal
exposures from the unloading of \ aricms containers (i.e., drums, tank trucks, rail cars) with pure NMP.
While EPA does expect that workers may perform additional activities during this scenario, such as
sampling or maintenance work, EPA expects thai unloading activities present the largest range of
potential exposures
Inhalation and Vapor-throuxli-Skin
EPA found limited monitoring data for the use of NMP in non-incorporative processing activities (e.g.,
use of NMP as an intermediate, as a media for synthesis, extractions, and purifications, or as some other
type of processing aid), and the monitoring data found lacks data on worker activities, the function of
NMP within the industry of use, and the sampling duration. Due to limited relevance and quality of
monitoring data and modeling estimates for chemical processing with NMP found in the published
literature, EPA used modeling estimates with the highest data quality for this use. The Drum Loading
and Unloading Release and Inhalation Exposure Model involves probabilistic modeling.
The inhalation exposure concentrations modeled by EPA for loading of NMP are summarized into the
input parameters used for the PBPK modeling in Table 2-11. The modeled exposure concentrations are
the same as those for Manufacturing and Repackaging; however, the exposure durations are different
because they are based on the NMP volume unloaded for the exposure scenario. Note that the exposure
duration for the central tendency and high-end exposure scenarios are the same because the unloading
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rate does not vary in this model. The supplemental document Risk Evaluation for N-Methylpyrrolidone
(2-Pyrrolidinone, 1 Methyl-) (NMP), Supplemental Information on Occupational Exposure Assessment
( 2019f) provides additional details.
Table 2-11. Summary of Parameters for PBPK Modeling of Worker Inhalation Exposure During
Chemical Processing
Work
Activity
Parameter
( haracleri/ation
lull-Shift NMP
Air
Concentration
Duration-liascd
NMP Air
Concentration
Source
Data
Quality
Rating
(mg/nr\ 8-hr
TWA)
(nig/m')
Unloading
liquid NMP
from drums
Central tendency
(50th percentile)
0.075
1 (o (duration
i) 30 hi )
/ h um I oailmi:
and 1 n/oaihng
Release and
Inhalation
Exposure
Model flJ.S.
EPA. 2013a)
Not
applicable11
High-end (95th
percentile)
0.265
5.S5 (duration =
<).3o hi )
a - EPA models are standard sources used by EPA for occupational exposure assessments. EPA did not systematically review
models that were developed by EPA.
Dermal
Table 2-12 summarizes the parameters used to assess dermal exposure during NMP use in non-
incorporative processing activities. EPA assessed dermal exposures during the unloading of pure NMP
from drums. Most of these parameters were determined based on assumptions described in Section
2.4.1.1. EPA used data from 2016 CI)R. public comments, and the Use and Market Profile for N-
Methylpyrrolidone ( i )) to delermi ne the NMP weight fraction. The underlying data rated by
EPA have data quality ratings of high Ik-cause this scenario has only industrial sites, EPA assumes that
workers are likely to wear protect! \ e glo\ es and ha\ e basic training on the proper usage of these gloves
for both central and high-end exposures, corresponding to a protection factor of 10.
Table 2-12. Summary of Parameters for Worker Dermal Exposure to Liquids During Chemical
Processing. Including Formulation
Work
Activity
Parameter
Characterization
(•love
Protection
l-"actor(s)
NMP
W eight
l-'raction
Skin
Surface
Area
K.\ posed 11
Kxposurc
Duration
liody
W eight
il
I n it less
cm2
lir/dav
kg
Unloading
liquid NMP
from drums
Central Tendency
10
1
445 (f)
535 (m)
0.36
74(f)
High-End
10
1
890 (f)
1,070 (m)
0.36
88 (m)
a EPA assessed these exposure factors for both females and males. Values associated with females are denoted with (f) and
values associated with males are denoted with (m).
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PBPK Inputs
EPA assessed PBPK parameters for central tendency and high-end exposure scenarios based on the
characterizations listed in Table 2-13.
The numeric parameters corresponding to the characterizations presented in Table 2-13 are summarized
in Table 2-14. These are the inputs used in the PBPK model.
Table 2-13. Characterization of PBPK Model Input Parameters for Chemical Processing,
Excluding Formulation
Scenario
Work
Activity
Air
Concentration
Data
Characterization
Exposure
Duration
Skin
Surface
Area
Exposed
(•loves
NMP Weight
l-'raction
Characterization
Central
Tendency
Unloading
drums
Central tendency
(50th percentile)
Duration
calculated
by model
1-hand
Yes
\ A - 100% is
assumed for both
exposure scenarios
High-end
Unloading
drums
High-end (95th
percentile)
Duration
calculated
by model
2-hand
Yes
N/A - 100% is
assumed for both
exposure scenarios
Table 2-14.
>BPK Model Input Parameters for Chemical Processing. Excluding Formu
ation
Scenario
Duralion-liascd
NMP Air
Concentration
(nig/nr*)
Exposure
Duration
(hr)
Skin
Surface
Area
Exposed
(Oil")
(•loves
Protection
l-'actor
NMP
\Y'eight
l-'raction
liodv
\Y'eight
(kg)"
Central
Tendency
1.65
0 3o
445(f)
535 (in)
10
1
74 (f)
88 (m)
High-end
5.85
0 36
890 (f)
1,070 (m)
10
1
74 (f)
88 (m)
a EPA assessed these exposure factors lor boili females and males. Values associated with females are denoted with (f) and
values associated with males are denoted Willi < in).
bEPA assessed a skin surface area exposed lo liquid NMP of 0.1 cm2for ONUs for each scenario. However, EPA did not
assess glo\ e nsaue (protection factor 1) for ONUs.
Summary
In summary, dermal and inhalation exposures are expected for this use. EPA has not identified
additional uncertainties for this use beyond those included in Section 2.4.1.4. EPA identified primary
strengths and limitations and assigned an overall confidence to the occupational exposure scenario
inputs to the PBPK model, as discussed below. EPA considered the assessment approach, the quality of
the data, and uncertainties to determine the level of confidence. Note that the effects of the limitations
on this assessment are discussed in Section 2.4.1.4.
Primary Strengths
EPA assessed dermal exposure to liquids using the most recent CDR data for concentration provided by
industry submitters. Modeling, in the middle of the approach hierarchy, was used to estimate
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occupational inhalation exposure concentrations for both the unloading of NMP from bulk containers
and from drums. For modeling of these air concentrations, EPA attempted to address variability in input
parameters by estimating both central tendency and high-end parameter values. Additionally, EPA used
Monte Carlo simulation to capture variability in input parameters. EPA expects the duration of
inhalation and dermal exposure to be realistic, as the duration is based on the length of time to load
NMP into drums.
Primary Limitations
The representativeness of the estimates of duration of inhalation and dermal exposure for the unloading
activities toward the true distribution of duration for all worker activities in this occupational exposure
scenario is uncertain. NMP concentration is reported to CDR as a range and I-PA assessed only the
upper end of the range since a central value cannot be ascertained for this scenario. Skin surface areas
for actual dermal contact are uncertain. EPA did not find data on the use of glo\ es for this occupational
exposure scenario and assumed glove usage is likely based on professional judgment The assumed
glove protection factor values are uncertain. EPA is uncertain of the accuracy of the emission factors
used to estimate fugitive NMP emissions and thereby to model NMP air concentrations The
representativeness of the modeling results toward the true distribution of i nhalation concentrations for
this occupational exposure scenario is uncertain.
Overall Confidence
Considering the overall strengths and limitations, the o\ erall confidence of the PBPK input parameters
for this occupational exposure scenario is medium.
2.4.1.2.4 Incorporation into Formulation, Mixture, or Reaction Product
This scenario includes the use of NMP for incorporation into a formulation, mixture or reaction product,
which refers to the process of mixing or blending of several raw materials to obtain a single product or
preparation. The uses of NMP that may require incorporation into a formulation include adhesives,
sealants, paints, coatings, inks, metal finishing chemicals, cleaning and degreasing products, agricultural
products, and petrochemical products including lube oils.
For this industrial exposure scenario. F.PA assessed inhalation, vapor-through-skin, and dermal
exposures from the unloading of \ arious containers (i.e., drums, tank trucks, rail cars) with pure NMP
and from maintenance, bottling, shipping, and loading of NMP in formulations.
Inhalation and I anor-throusili-Sldn
EPA compiled inhalation monitoring data and modeled exposure concentration data for the
incorporation of NMP into a formulation, mixture or reaction product. Because EPA favors the use of
monitoring data over modeled data, monitoring data with the highest data quality was used to assess
exposure for this use. EPA used the monitoring data for the central tendency and high-end full-shift
worker exposure concentrations presented in Table 2-15.
In addition to this monitoring data, EPA also modeled short-term worker inhalation exposure from
unloading NMP. The Drum Loading and Unloading Release and Inhalation Exposure Model involves
probabilistic modeling. The concentrations obtained from modeling are summarized into the input
parameters used for the PBPK modeling in Table 2-17 and Table 2-18. In addition to the formulation of
liquid products, EPA identified formulation activities that may result in potential worker exposures to
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solids containing NMP. EPA estimated inhalation exposure concentration of NMP in particulates;
however, EPA does not use these exposure concentrations as input to the PBPK model because the
PBPK model does not account for solids, and the range of input parameters for the other exposure
scenarios capture these concentrations. The supplemental document Risk Evaluation for N-
Methylpyrrolidone (2-Pyrrolidinone, 1 Methyl-) (NMP), Supplemental Information on Occupational
Exposure Assessment ( 2019r) provides additional details.
Table 2-15. Summary of Parameters for PBPK Modeling of Worker Inhalation Exposure During
Incorporation into Formulation, IV
ixture or Reaction Product
Work
Activity
Parameter
Characterization
lull-Shift
NMP Air
Concentration
Duration-
liased NMP
Air
Concentration
Source
Data
Quality
Rating
(mg/nr\ 8-hr
TWA)
(nig/nr')
Unloading
liquid NMP
from drums
Central Tendency
(50th percentile)
0 075
1.65 (duration
= 0 30 lir)
Drum Loading
and Unloading
Release and
Inhalation
Exposure
Model (US.
UFA. 2013 a)
Not
applicable11
Maintenance,
bottling,
shipping,
loading
1 Muli-end (^5'''
percenli 1 e)
12.8
No data
(Bader et al..
2006)
High
Loading
solids into
drums
Central Tendency
(5<)lh peivenlile)
0.75
No data
EPA'sOSHA
PNOR PEL
model (
EPA. 2013a)
and NMP
concentration
data
Not
applicable
1 Hull-end (l>5lh
percenli 1 e)
0.96
No data
a - EPA models arc slandanl sources used by EPA for occupational exposure assessments. EPA did not systematically
review models llial uere de\ eloped h\ I PA
Dermal
Table 2-16 summarizes the parameters used to assess dermal exposure during the incorporation of NMP
into formulations, mi Mures, and reaction products. For this life cycle stage, EPA assessed dermal
exposures during the unloading of pure NMP from drums. As indicated above, the PBPK model does
not account for solids so EPA did not include loading of solids in the dermal parameter summary. Most
of these parameters were determined based on assumptions described in Section 2.4.1.1. EPA used data
from 2016 CDR, public comments, literature, and the Use and Market Profile for N-Methylpyrrolidone
(Abt. 2017) to determine the NMP weight fraction. The underlying data rated by EPA have data quality
ratings ranging from medium to high. Because this scenario has only industrial sites, EPA assumes that
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workers are likely to wear protective gloves and have basic training on the proper usage of these gloves
for both central and high-end exposures, corresponding to a protection factor of 10.
Table 2-16. Summary of Parameters for Worker Dermal Exposure to Liquids During
Incorporation int
o Formulation, Mixt
ture, or Reaction Product
Work Activity
Parameter
Characterization
(•love
Protection
l-"actor(s)
NMP
Weight
l-'raction
Skin
Surface
Area
Kx posed 11
Kxposure
Duration
Body
Weight
;i
I nitless
cm2
lir/dav
kg
Unloading
liquid NMP
from drums
Central Tendency
10
1
445 (f)
535 (m)
0.36
74 (f)
88 (m)
Maintenance,
bottling,
shipping,
loading
High-End
10
1
890 (f)
1.070 (m)
8
74 (f)
88 (m)
11 EPA assessed these exposure factors for both females and males. Values associated with females are denoted with (f) and
values associated with males are denoted with (m).
PBPK Inputs
EPA assessed PBPK parameters for central tendency and high-end exposure scenarios based on the
characterizations listed in Table 2-17. EPA only presents these scenarios for handling of liquid NMP, to
present conservative assessments of potential exposures
The numeric parameters corresponding to the characterizations presented in Table 2-17 are summarized
in Table 2-18. These are the inputs used in the PBPK model.
Table 2-17. Characterization of I'BPK Model Input Parameters for Incorporation into
Formulation, Mixture or Reaction Product
Scenario
Work
Activity
Air
Concentration
Data
Characterization
Kxposure
Duration
Skin
Surface
Area
Kxposed
(•loves
NMP Weight
Traction
Characterization
Central
Tendency
I nloading
drums
Central tendency
(50th percentile)
Duration
calculated
by model
1-hand
Yes
N/A - 100% is
assumed for both
exposure scenarios
High-end
Maintenance,
bottling,
shipping,
loading
High-end (95th
percentile)
Duration
calculated
by model
2-hand
Yes
N/A - 100% is
assumed for both
exposure scenarios
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Table 2-18. PBPK Model Input Parameters for Incorporation into Formulation, Mixture or
Reaction Product
Hand
Duralion-liascd
Surface
liodv
NMP Air
Kxposurc
Area
(•loves
NMP
Weight
Concentration
Duration
K.\ posed
Protection
Weight
(kg)"
Scenario
(nig/nr*)
(lir)
(cm2)11 h
l-actor
l-'raction
Central
Tendency
1.65
0.36
445 (f)
535 (m)
10
1
74(f)
88 (m)
High-end
12.8
8
890 (f)
1,070 (m)
10
1
74(f)
88 (m)
a Calculated based on the duration-based air concentration and exposure duration. S-Ikuii 1 \\ \ (Duration-based air
concentration)
x (Exposure durationV8 hours.b EPA assessed these exposure factors for bolh females and males.a EPA
assessed these exposure factors for both females and males. Values associated with females arc dcnoicd with (f) and
values associated with males are denoted with (m).
bEPA assessed a skin surface area exposed to liquid NMP of 0.1 enf for ONUs for each scenario. How e\ or. 1 PA did not
assess glove usage (protection factor = 1) for ONUs.
Summary
In summary, dermal and inhalation exposures are expected for this use EPA has not identified
additional uncertainties for this use beyond those included in Section 2 4 14. EPA identified primary
strengths and limitations and assigned an overall confidence to the occupational exposure scenario
inputs to the PBPK model, as discussed below l-IW considered the assessment approach, the quality of
the data, and uncertainties to determine the level of confidence Note that the effects of the limitations
on this assessment are discussed in Section 2.4.1 4
Primary Strengths
EPA assessed dermal exposure to liquids using the most recent CDR data for concentration provided by
industry submitters. Modeling, in the middle of the approach hierarchy, was used to estimate
occupational inhalation exposure concentrations for the unloading of NMP from drums. For modeling of
these air concentrations, EPA attempted to address \ ariability in input parameters by estimating both
central tendency and high-end parameter \ alues. Additionally, EPA used Monte Carlo simulation to
capture \ ariability in input parameters I-PA expects the duration of inhalation and dermal exposure to
be realistic, as the duration is based on the length of time to load NMP into drums. EPA assessed worker
inhalation exposure during maintenance, bottling, shipping, and loading of NMP using directly
applicable monitoring data, which is the highest of the approach hierarchy, taken at an adhesive
formulation faci lily The data quality rating for the monitoring data used by EPA is high. EPA expects
the duration of inhalation and dermal exposure to be realistic for the unloading of drums, as the duration
is based on the length of time to load NMP into drums.
Primary Limitations
The representativeness of the estimates of duration of inhalation and dermal exposure for the assessed
activities toward the true distribution of duration for all worker activities in this occupational exposure
scenario is uncertain. NMP concentration is reported to CDR as a range and EPA assessed only the
upper end of the range since a central value cannot be ascertained for this scenario (NMP concentration
is lower in the formulated products). Skin surface areas for actual dermal contact are uncertain. EPA did
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not find data on the use of gloves for this occupational exposure scenario and assumed glove usage is
likely based on professional judgment. The assumed glove protection factor values are uncertain.
EPA estimated worker inhalation exposure concentration during the loading of NMP in solid
formulations using EPA's OSHA PEL for PNOR model (U.S. EPA. 2013a). which is the lowest
approach on the hierarchy. EPA did not use these inhalation exposure concentrations for the PBPK
modeling because the PBPK model does not account for solids and because both the inhalation and
dermal exposure potential are captured within other occupational exposure scenarios. EPA is uncertain
of the accuracy of the emission factors used to estimate fugitive NMP emissions and thereby to model
NMP air concentrations. For the maintenance, bottling, shipping, and loading of liquid NMP, the
monitoring data consists of only 7 data points from 1 source. The representativeness of the modeling and
the monitoring data toward the true distribution of inhalation concentrations lor these occupational
exposure scenarios is uncertain.
Overall Confidence
Considering the overall strengths and limitations, 1he o\ era 11 confidence of the PBPK input parameters
for this occupational exposure scenario is medium.
2.4.1.2.5 Metal Finishing
This scenario includes the use of metal finishing products containing \MP. For this industrial and
commercial exposure scenario, EPA assessed inhalation, vapor-through-skin, and dermal exposures to
metal finishing products containing NMP from the following application methods:
• Spray application;
• Dip application; and
• Brush application.
While EPA does expect that workers may perform additional activities during this scenario, such as
unloading or sampling, EPA expects that application acti vities present the largest range of potential
exposures.
Inhalation and Vapor-throush-Skin
EPA compiled inhalation monitoring data for NMP-based metal finishing applications from published
literature sources, including 8-hour TW.V short-term and partial shift sampling results. Where available,
EPA used monitoring data for metal finishing or surrogate monitoring data (surrogate work activities
using NMP) for the use of NMP during the Application of Paints, Coatings, Adhesives, and Sealants
(Section 2.4.1.2 5) and Cleaning (Section 2.4.1.2.10) that had the highest quality rating to assess
exposure. Where monitoring data were unavailable for an application type, EPA used modeling
estimates with the highest data quality to assess exposure.
EPA found limited data on the application of metal finishing chemicals and thus assessed spray
application using data from the Application of Paints, Coatings, Adhesives, and Sealants occupational
exposure scenario (Section 2.4.1.2.5) as a surrogate for the worker activities in this occupational
exposure scenario. EPA also used data for dip cleaning from the Cleaning occupational exposure
scenario (Section 2.4.1.2.10) as a surrogate for the worker activities in this occupational exposure
scenario. EPA used these data as surrogate because of the lack of more applicable data and due to the
similarity in work activities (e.g., spray and dip activities are similar between these OESs) between the
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occupational exposure scenarios. Finally, EPA used a modeled exposure estimate for the brush
application of a substance containing NMP.
The monitoring data and the modeled exposure estimates for metal finishing are summarized according
to the input parameters used for the PBPK modeling in Table 2-19. The supplemental document Risk
Evaluation for N-Methylpyrrolidone (2-Pyrrolidinone, 1 Methyl-) (NMP), Supplemental Information on
Occupational Exposure Assessment (U.S. EPA. 2019r) provides additional details.
Table 2-19. Summary of Parameters for PBPK Modeling of Worker I nhalalion Exposure During
Metal Finishing
Work
Activity
Parameter
Characterization
lull-Shift
\MP Air
Concentration
Duration-
liased NMP
Air
Concentration
Source
Data
Quality
Rating
(mg/nr\ 8- lir
TWA)
(nig/nr*)
Spray
Application
Low-end (of
range)
0.04
ii i)4 (duration
4 hi )
r tt'ish. 1998)
High
Mean
i) 53
ii 53 (duration =
4 hr)
High-end (of
range)
4 51
4 5 1 (duration
4 hi)
Dip
Application
Central Tendency
(50th percentile)
0.99
No data
Surrogate data
(surrogate work
activities using
NMP) from:
(RIVM. 2013;
Nishirrmra et al..
2.009; Bader et
al.. 2006; Xiaofei
et al.. 2000)
( )
Medium
to high
1 Muli-end (l>5lh
percentile)
2.75
No data
liiusli
Application
Single estimate
4.13
No data
(RIVM. 2013)
High
Dermal
Table 2-20 summarizes the parameters used to assess dermal exposure during application of metal
finishing formulations containing NMP. Most of these parameters were determined based on
assumptions described in Section 2.4.1.1. EPA used data from the 2012 and 2016 CDR to determine the
NMP weight fraction, which indicate that the weight concentration of NMP in formulation is greater
than 60 percent but less than 90 percent. Due to lack of additional information, EPA assesses a low-end
weight fraction of 0.6 and a high-end weight fraction of 0.9. The CDR data have a data quality rating of
high. Because this scenario covers a variety of commercial and industrial sites, EPA assumes that either
no gloves are used or, if gloves are used, that there is no permeation data to indicate the glove material is
protective for NMP, corresponding to a protection factor of 1. EPA assesses a central tendency scenario
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assuming the use of gloves with minimal to no employee training, corresponding to a protection factor
of 5.
Table 2-20. Summary of Parameters for Worker Dermal Exposure to Liquids During Metal
Finishing i
Work
Activity
Parameter
Characterization
(•love
Protection
l-"actor(s)
YMP
\Y'eight
l-'raction
Skin
Surface
Area
Kx posed 11
Kxposurc
Duration
liody
\\ eight
il
I n it less
cm2
lir/dav
kg
All forms of
application
listed above
Central Tendency
5
0.6
445 (f)
535 (in)
4
74 (f)
High-end
1
0.9
890 (f)
1,070 (m)
S
88 (m)
EPA assessed these exposure factors for both females and males \ allies associated with females* are dcnoicd \\ nil (f) and
values associated with males are denoted with (m).
PBPK Inputs
EPA assessed PBPK parameters for central tendency and high-end exposure scenarios based on the
characterizations listed in Table 2-21.
The numeric parameters corresponding to the characterizations presented in Table 2-21 are summarized
in Table 2-22. These are the inputs used in the PlJI'k model
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1784 Table 2-21. Characterization of PBPK Model Input Parameters for Metal Finishing
Scenario
W ork Activity
Air Concentration
Data
Characterization
Kxposure
Duration
Skin Surface
Area
Kxposed
(•loves
YMP W eight l-'raction
Characterization
("cnli ill Tendency
Spray application
Mean
Assumed 4 hours
l-hand
Yes
Central Tendency
High-end
Spray application
High-end (of range)
Assumed 8 hours
2-hand
\o
High-end
Central Tendency
Dip application
Central Tendency (50th
percentile)
Assumed 4 hours
1 -hand
Yes
C entral Tendency
High-end
Dip application
High-end (95th
percentile)
Assumed 8 hours
2-hand
No
High-end
Central Tendency
Brush application
Single estimate
Assumed 4 hours
l-hand
Yes
Central Tendency
High-end
Brush application
Single estimate
Assumed 8 hours
2-hand
No
High-end
1785
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Table 2-22. PBP1
¦C Model Input
Parameters for Metal
finishing
Scenario
Work
Activity
Duration-Based NMP
Air Concentration
(nig/in')
Kxposurc
Duration (lir)
Skin Surface Area
Kxposcd (cm2)ll h
(•loves
Protection
l-'actor
NMP Weight
l-'raction
liody
W eight
(kg)11
Central
Tendency
Spray
application
i) 53d
4
445 (f)
535 (m)
5
0.6
74(f)
88 (m)
High-end
Spray
application
4 51
8
XW (f)
I.D70 (m)
1
0.9
74(f)
88 (m)
Central
Tendency
Dip
application
1 ox
4
445 (f)
535 (m)
5
0.6
74(f)
88 (m)
High-end
Dip
application
2.75
S
890 (f)
1,070 (m)
1
0.9
74(f)
88 (m)
Central
Tendency
Brush
application
8 26
4
445 (f)
535 (m)
5
0.6
74(f)
88 (m)
High-end
Brush
application
4 13
8
890 (f)
1,070 (m)
1
0.9
74(f)
88 (m)
a EPA assessed these exposure factors for both females and males. Values associated with females are denoted with (f) and values associated with males are denoted
with (m).
bEPA assessed a skin surface area exposed to liquid NMP of u. 1 cm2for ONUs for each scenario. However, EPA did not assess glove usage (protection factor = 1) for
ONUs.
1788
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Summary
In summary, dermal and inhalation exposures are expected for this use. EPA has not identified
additional uncertainties for this use beyond those included in Section 2.4.1.4. EPA identified primary
strengths and limitations and assigned an overall confidence to the occupational exposure scenario
inputs to the PBPK model, as discussed below. EPA considered the assessment approach, the quality of
the data, and uncertainties to determine the level of confidence. Note that the effects of the limitations
on this assessment are discussed in Section 2.4.1.4.
Primary Strengths
EPA assessed dermal exposure to liquids using the most recent CDR data for concentration provided by
industry submitters. To estimate inhalation exposure during spray application, EPA used surrogate
monitoring data (surrogate work activities using NMP), which is in the middle of the approach
hierarchy, including 26 data points. These data have a data quality rating of high. To estimate inhalation
exposure during dip application, EPA used surrogate monitoring data for the use of NMP design dip
cleaning, which is in the middle of the approach hierarchy, including data from 5 sources These data
have data quality ratings of medium to high. To estimate inhalation exposure during hush application,
EPA used modeled data from the RIVM report (RIVM. ). w liich has a data quality rating of high.
The use of modeling is in the middle of the approach hierarchy I -P A used durations associated with
inhalation monitoring data to estimate duration of inhalation and dermal exposure during spray
application.
Primary Limitations
EPA did not find exposure data for this occupational exposure scenario and used surrogate or modeled
data to assess occupational inhalation exposures. For occupational exposure scenarios other than spray
application, EPA did not find exposure duration data and assumed a high-end of 8 hours because the
surrogate data or modeled values are S-hour TWA values. EPA assumed a mid-range of 4 hours for
central tendency exposure duration The representativeness of the assumed estimates of duration of
inhalation and dermal exposure lor the assessed activities toward the true distribution of duration for all
worker activities in this occupational exposure scenario is uncertain. Due to lack of data, EPA could not
calculate central tendency and high-end NMP concentration in metal finishing products and used the
low-end and high-end of the \'V1P concentration range reported in 2016 CDR. Skin surface areas for
actual dermal contact are uncertain. EP A did not find data on the use of gloves for this occupational
exposure scenario and assumed glove usage with minimal to no employee training or no glove usage due
to the potential w ide-spread use of metal finishing products. The assumed glove protection factor values
are uncertain The a\ ailable monitoring data for spray application is from 1996. The extent to which
these data are representative of current worker inhalation exposure potential is uncertain. The worker
activities associated with the surrogate data used to assess worker inhalation exposure during dip
application are not detailed for all sample points. The modeled inhalation exposure concentration during
roller/brush application was obtained from RIVM (2013) and not generated by EPA. For all
occupational exposure scenarios, representativeness of the monitoring data, surrogate monitoring data,
or modeled data toward the true distribution of inhalation concentrations for this occupational exposure
scenario is uncertain.
Overall Confidence
Considering the overall strengths and limitations, the overall confidence of the PBPK input parameters
for this occupational exposure scenario is medium.
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2.4.1.2.6 Removal of Paints, Coatings, Adhesives and Sealants
This scenario includes the use of paint, coating, adhesive, and sealant removal products containing
NMP. For this industrial and commercial exposure scenario, EPA assessed inhalation, vapor-through-
skin, and dermal exposures to paint, coating, adhesive, and sealant removal products containing NMP
from the following activities:
• Miscellaneous paint and coating removal; and
• Graffiti removal.
While EPA does expect that workers may perform additional activities during this scenario, such as
unloading or sampling, EPA expects that removal activities present the largest range of potential
exposures.
Worker activities for the removal of paints, coatings, adhesives, and sealants involve the application of
products containing high concentrations of NMP onto open surfaces from which e\ aporalion will occur.
This results in higher NMP air concentrations and potential worker exposures relali\ e to oilier
occupational exposure scenarios in this risk evaluation.
Inhalation and Vayor-through-Skin
EPA compiled inhalation monitoring data for NMP-based paint, coating, adhesive, and sealant removal
from published literature sources, including S-hour TWA, short-term, and partial shift sampling results.
This data is summarized into low-end (lowest concentration), high-end (highest concentration), and
mean or mid-range values in Table 2-23. EPA used the a\ ailablc monitoring data with the highest data
quality to assess exposure for this use. The data presented in TaMe 2-23 are the input parameters used
for the PBPK modeling for workers. The supplemental document Risk Evaluation for N-
Methylpyrrolidone <2-l'yrroluliiioiie. / \ /ethyl-) (NMP), Supplemental Information on Occupational
Exposure Assessment ( ) pro\ ides additional details.
Table 2-23. Summary of Parameters for PliPIv Modeling of Worker Inhalation Exposure During
Removal of Paints.
Coatings. Adhesives and Sealants
Work Activity
Parameter
( haracleri/ation
lull-Shift NMP
Air
Concentration
Dm ration-Based
NMP Air
Concentration
Sonrce
Data
Quality
Rating
(ing/nr*. 8-hr
TWA)
(nig/nr*)
Miscellaneous
paint, coating,
adhesive, and
sealant removal
Low end (of
range)
1.0
6.1 (duration = 1
hr)
(U.S.
EPA,
2.015)
High
Mid-range
32.5
13.2 (duration = 1
hr)
High end (of
range)
64
280 (duration = 1
hr)
Graffiti removal
Low end (of
range)
0.03
No data
(
High
Mean
1.01
No data
EPA.
2015)
High end (of
range)
4.52
No data
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Dermal
Table 2-24 summarizes the parameters used to assess dermal exposure during paint, coating, adhesive,
and sealant removal. Most of these parameters were determined based on assumptions described in
Section 2.4.1.1. EPA used data from public comments, literature sources, and the Use and Market
Profile for N-Methylpyrrolidone (Abt 2017) to determine the NMP weight fraction. The underlying data
have data quality ratings ranging from medium to high. One anecdotal survey of glove usage among
workers performing graffiti removal indicates that most workers wear gloves, although the glove
materials varied and were sometimes not protective (U.S. EPA. 2015). Because this scenario covers a
variety of commercial and industrial sites, EPA assumes that either no gloves are used or, if gloves are
used, there is no permeation data to indicate the glove material is protecti\ e for NMP, corresponding to
a protection factor of 1. EPA assesses a central tendency scenario assuming the use of gloves with
minimal to no employee training, corresponding to a protection factor of 5.
Table 2-24. Summary of Parameters for PBPK Modeling of Worker Dermal Kxposure to Liquids
Work Activity
Parameter
Characterization
(Jove
Protection
l'"actor(s)
NMP
Weight
Kraction
Skin
Surface
Area
Kxposed "
Kxposure
Duration
liodv
Weight
il
I n it less
cm2
lir/dav
kg
Miscellaneous
paint, coating,
adhesive, and
sealant removal
Central Tendency
5
i) 3i)5
445(f)
535 (m)
1
74
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1890 Table 2-25. Characterization of PBPK Model Input Parameters for Removal of Paints, Coatings,
1891 Adhesives and Sealants
Scenario
Work
Activity
Air
Concentration
Data
Characterization
Kxposurc
Duration
Skin
Surface
Area
Kxposcd
(•loves
YM P Weight
l-'raction
Characterization
Central
Tendency
Miscellaneous
paint, coating,
adhesive, and
sealant
removal
Mid-range
Based on
1-hr
TWA
data
1-hand
Yes
Central Tendency
High-end
Miscellaneous
paint, coating,
adhesive, and
sealant
removal
High-end (of
range)
Assumed
8 hours
2-hand
No
1 ligh-end
Central
Tendency
Graffiti
removal
Mean
Assumed
4 hours
l-hand
Yes
Central Tendency
High-end
Graffiti
removal
High-end (of
range)
Assumed
S hours
2-hand
No
High-end
1892
1893
1894 Table 2-26. PBPK Model Input Parameters for Removal of Paints. Coalings, Adhesives and
1895 Sealants
Scenario
Work Activity
Duralion-liascd
NMP Air
Concentration
(nig/nr*)
Kxposurc
Duration
(In)
Skin
Surface
Area
Kxposed
(cm2)11 h
(•loves
Protection
l-'actor
NMP
Weight
Kraction
liody
Weight
(IvS) ='
Central
Tendency
Miscellaneous
paint, coaling,
adheshe. and
sealant removal
13 2
1
445 (f)
535 (m)
5
0.305
74 (f)
88 (m)
High-end
Miscellaneous
painl. coating.
adhesi\e. and
sealant remo\al
64
8
890 (f)
1,070 (m)
1
0.695
74 (f)
88 (m)
Central
Tendency
Graffiti remo\ al
2.02
4
445 (f)
535 (m)
5
0.5
74 (f)
88 (m)
High-end
Graffiti removal
4.52
8
890 (f)
1,070 (m)
1
0.613
74 (f)
88 (m)
a EPA assessed these exposure factors for both females and males. Values associated with females are denoted with (f) and
values associated with males are denoted with (m).
bEPA assessed a skin surface area exposed to liquid NMP of 0.1 cm2for ONUs for each scenario. However, EPA did not
assess glove usage (protection factor = 1) for ONUs.
1896
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Summary
In summary, dermal and inhalation exposures are expected for this use. EPA has not identified
additional uncertainties for this use beyond those included in Section 2.4.1.4. EPA identified primary
strengths and limitations and assigned an overall confidence to the occupational exposure scenario
inputs to the PBPK model, as discussed below. EPA considered the assessment approach, the quality of
the data, and uncertainties to determine the level of confidence. Note that the effects of the limitations
on this assessment are discussed in Section 2.4.1.4.
Primary Strengths
EPA assessed dermal exposure to central tendency and high-end N\IP weight fractions, calculated as
the 50th and 95th percentiles, respectively, from a variety of data son ices with data quality ratings
ranging from medium to high. To estimate inhalation exposure during miscellaneous paint and coating
removal, EPA used directly applicable personal monitoring data, the highest of the approach hierarchy,
including data from three studies. These data have a dal a quality rating of high. To estimate inhalation
exposure during graffiti removal, EPA used directly applicable personal monitoring data, the highest of
the approach hierarchy, including 25 data points. These data have a data quality rating of high. EPA
used durations associated with inhalation monitoring data to estimate duration of inhalation and dermal
exposure during miscellaneous paint, coating, adhesive, and sealant removal.
Primary Limitations
For graffiti removal, EPA did not find dala other than X-hour TWA \ allies I-PA assumed a high-end
exposure duration equal to 8 hours and a central tendency exposure duration of 4 hours, which is the
mid-range of a full shift. The representativeness of the assumed estimates of duration of inhalation and
dermal exposure for the assessed activities toward the true distribution of duration for all worker
activities in this occupational exposure scenario is uncertain. EPA did not find data on the use of gloves
for this occupational exposure scenario and assumed glove usage with minimal to no employee training
or no glove usage due to the wide-spread use of removal products. The assumed glove protection factor
values are uncertain.
The short-term inhalation exposure concentrations for miscellaneous removal are based on data from
1993 and the extent to which these data are representative of current worker inhalation exposure
potential is uncertain I or grafliti remo\ al. EPA used the minimum, mean, and maximum air
concentrations reported by one literature source for 25 datapoints. EPA did not have these 25 data points
with which to calculate 50th and l^5th percentile values. The representativeness of the monitoring data
toward the true distribution of inhalation concentrations for this occupational exposure scenario is
uncertain.
Overall Confidence
Considering the overall strengths and limitations, the overall confidence of the PBPK input parameters
for this occupational exposure scenario is medium.
2.4.1.2.7 Application of Paints, Coatings, Adhesives and Sealants
This scenario includes the application of paints, coatings, adhesives, and sealants containing NMP. For
this industrial and commercial exposure scenario, EPA assessed inhalation, vapor-through-skin, and
dermal exposures to paints, coatings, adhesives, and sealants containing NMP from the following
application methods:
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• Spray application;
• Roll / curtain application;
• Dip application; and
• Roller / brush and syringe / bead application.
While EPA does expect that workers may perform additional activities during this scenario, such as
unloading or sampling, EPA expects that application activities present the largest range of potential
exposures.
Inhalation and Vayor-throush-Skin
EPA compiled inhalation monitoring data and modeled exposure data for WIP-based paint, coating,
adhesive, and sealant application from published literature sources, including K-hour TWA, short-term,
and partial shift sampling results. Where available, EPA compiled surrogate monitoring data (surrogate
work activities using NMP) for the use of NMP during cleaning, which is described in Section
2.4.1.2.10. Where monitoring data were unavailable for an application type, EPA used surrogate
monitoring data (surrogate work activities using NMP) or modeling estimates with the highest data
quality to assess exposure, as further described below.
EPA found limited to no inhalation monitoring data on roll / curtain application, dip application, or
roller /brush and syringe / bead application with \\lP-containing formulations, so either surrogate data
for the use of NMP during the Cleaning occupational exposure scenario or modeling data were used to
determine the modeling parameters for these application methods The KPA/OPPT tIVRoll Coating
Model was used for roll / curtain coating application and in\ ol\ ed deterministic modeling.
The monitoring data and the modeled exposures for this life cycle stage are summarized in Table 2-27.
The supplemental document Risk I .valuation for N-Mel hylpyrrolidone (2-Pyrrolidinone, 1 Methyl-)
(NMP), Supplemental Information on (hx upational Exposure Assessment ( ) provides
additional details.
Table 2-27. Summary of Parameters for Plil'k Modeling of Worker Inhalation Exposure During
Application
Work
Activity
Parameter
Characterization
lull-Shift
NMP Air
Concentration
Duration-
liasetl NMP
Air
Concentration
Source
Data
Quality
Rating
(nig/in'. 8-hr
TWA)
(nig/nr*)
Spray
Application
] .ou-eiul (of
range)
0.04
0.04 (duration
= 4 hr)
fNios: i)
High
Mean
0.53
0.53 (duration
= 4 hr)
High-end (of
range)
4.51
4.51 (duration
= 4 hr)
Central Tendency
(50th percentile)
0.03
No data
EPA/OPPT UV
Roll Coating
Not
applicable21
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Work
Activity
Roll
Curtain
Application
Piirsimclcr
Chsimclcrizsition
liill-Shil't
NMP Air
('onccnlrsilion
Dursition-
lisisrd NMP
Air
Conccnlriilion
Source
loi/cl (
¦> x)
Qiiiilily
Kill in«
\ 8-hr
TWA)
(in»/in!)
High-end (95lh
percentile)
0.19
No data
Dip
Application
Central Tendency
(50th percentile)
0.99
No data
Surrogate data
(surrogate work
acli\ ilies using
NMP) iVonr
(R1V.P' ' ;
IF A. 2010;
Nishimura . ¦ .
2009; Bac
al.„ 2006; Xiaofei
et aL 2000)
Medium
to high
High-end (95th
percentile)
2.75
No data
Roller /
Brush and
Syringe /
Bead
Application
Single estimate
4.13
No data
( /M. 2013)
High
a - EPA models arc standard sources used by EPA for occupational exposure assessments. EPA did not systematically review
models that were developed bv EPA.
Dermal
Table 2-28 summarizes the parameters used to assess dermal exposure during application of paints,
coatings, adhesives. and sealants containing NMP. Most of these parameters were determined based on
assumptions described in Section 2.4.1 I EPA used data from public comments, literature, and the Use
and Market Profile Jor \-.\ Iciliylpyrrolnlone (Abt. 2017) to determine the NMP weight fraction. The
underlying data rated by EPA have data quality ratings ranging from medium to high. Because this
scenario co\ ers a variety of commercial and industrial sites, EPA assumes that either no gloves are used
or, if glo\ es are used, there is no permeation data to indicate the glove material is protective for NMP,
corresponding to a protection factor of 1. EPA assesses a central tendency scenario assuming the use of
gloves with minimal to no employee training, corresponding to a protection factor of 5.
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Table 2-28. Summary of Parameters for Worker Dermal Exposure to Liquids During Application
of Paints, Coatings, Adhesives and Sealants
Work
Activity
Parameter
Characterization
(•love
Protection
Kaclor(s)
YMP
W eight
l-'raction
Skin
Surface
Area
Kx posed 11
Kxposurc
Duration
liody
W eight
il
I n it less
cm2
lir/dav
Ivg
All forms of
application
listed above
Central Tendency
5
0.02
445 (f)
535 (m)
4
74 (f)
High-End
1
0.534
890 (f)
l,07o (mi
8
88 (m)
a EPA assessed these exposure factors for both females and males. Values associated wiili females are denoted with (f) and
values associated with males are denoted with (m).
PBPK Inputs
EPA assessed PBPK parameters for central tendency and high-end exposure scenarios Ixised on the
characterizations listed in Table 2-29.
The numeric parameters corresponding to the characterizations presented in Table 2-29 are summarized
in
Table 2-30. These are the inputs used in the PlJI'k model
Table 2-29. Characterization of PBPK Model Input Parameters for Application of Paints,
Coatings, Adhesives, and Sealants
Scenario
Work
Activity
Air
Concentration
Data
Characterization
Kxposurc
Duration
Skin
Surface
Area
Kxposed
(•loves
YM P W eight
Kraction
Characterization
Central
Tendency
Spray
application
Mean
Based on
1-hr TWA
data
1-hand
Yes
Central Tendency
High-end
Spray
application
High-end (of
range)
Based on
8-hr TWA
data
2-hand
No
High-end
Central
Tendency
Roll /
curtain
application
Central tendency
(50th percentile)
Assumed
4 hours
1-hand
Yes
Central Tendency
High-end
Roll/
curtain
application
High-end (95th
percentile)
Based on
8-hr TWA
data
2-hand
No
High-end
Central
Tendency
Dip
application
Central tendency
(50th percentile)
Assumed
4 hours
1-hand
Yes
Central Tendency
High-end
Dip
application
High-end (95th
percentile)
Based on
8-hr TWA
data
2-hand
No
High-end
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Scenario
Work
Activity
Air
Concentration
Data
Characterization
Kxposurc
Duration
Skin
Surface
Area
Kxposed
(•loves
Y\IP Weigh!
Kraction
Characterization
Central
Tendency
Brush
application
Single estimate
Assumed
4 hours
1-hand
Yes
Central Tendency
High-end
Brush
application
Single Estimate
Based on
8-hr TWA
data
2-hand
No
High-end
2003
2004 Table 2-30. PBPK Model Input Parameters for Application of Paints. Coalings, Adhesives and
2005 Sealants
Scenario
Work
Activity
Duralion-liascd
NMP Air
Concentration
(ing/nr')
Kxposurc
Duration
(In)
Skin
Surface
Area
Kxposed
(cm2)11 h
(Jove
Protection
Kactor
NMP
W eight
Kraction
liody
W eight
(kg)"
Ccn lial
Tendency
Spray
application
0.530
4
445 (f)
535 (in)
5
0.02
74 (f)
88 (m)
High-end
Spray
application
4.51
S
XW (f)
l.i)7i) Cm)
1
0.534
74 (f)
88 (m)
Central
Tendency
Roll/
curtain
application
I) ()(i
4
445 (1')
535 (m)
5
0.02
74 (f)
88 (m)
High-end
Roll/
curtain
application
0 I1)
8
890 (f)
1,070 (m)
1
0.534
74 (f)
88 (m)
Central
Tendency
Dip
iip plication
1
4
445 (f)
535 (m)
5
0.02
74 (f)
88 (m)
High-end
Dip
application
2.75
8
890 (f)
1,070 (m)
1
0.534
74 (f)
88 (m)
Central
Tendency
li rush
application
S 26
4
445 (f)
535 (m)
5
0.02
74 (f)
88 (m)
High-end
Brush
application
4.13
8
890 (f)
1,070 (m)
1
0.534
74 (f)
88 (m)
a EPA assessed these exposure factors for both females and males. Values associated with females are denoted with (f) and
values associated with males are denoted with (m).
bEPA assessed a skin surface area exposed to liquid NMP of 0.1 cm2for ONUs for each scenario. However, EPA did not
assess glove usage (protection factor = 1) for ONUs.
2006
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Summary
In summary, dermal and inhalation exposures are expected for this use. EPA has not identified
additional uncertainties for this use beyond those included in Section 2.4.1.4. EPA identified primary
strengths and limitations and assigned an overall confidence to the occupational exposure scenario
inputs to the PBPK model, as discussed below. EPA considered the assessment approach, the quality of
the data, and uncertainties to determine the level of confidence. Note that the effects of the limitations
on this assessment are discussed in Section 2.4.1.4.
Primary Strengths
EPA assessed dermal exposure to central tendency and high-end N\IP weight fractions, calculated as
the 50th and 95th percentiles, respectively, from a variety of data son ices with data quality ratings
ranging from medium to high. To estimate inhalation exposure during spray application, EPA used
directly applicable personal monitoring data, the highest of the approach hierarchy, including 26 data
points. These data have a data quality rating of high. To estimate inhalation exposure dining roll/curtain
application, EPA used modeling, which is in the middle of the approach hierarchy. To estimate
inhalation exposure during dip application, EPA used surrogate monitoring data for the use of NMP
during dip cleaning, which is in the middle of the approach hierarchy, including data from 5 sources.
These data have data quality ratings of medium to high. To estimate inhalation exposure during roller /
brush and syringe/bead application, EPA used modeled data from the RIVM report (RIVM. 2013).
which has a data quality rating of high. The use of modeling is in the middle of the approach hierarchy.
EPA used durations associated with short-term inhalation monitoring data to estimate duration of
inhalation and dermal exposure during spray application.
Primary Limitations
For occupational exposure scenarios other than spray application, I-PA did not find exposure duration
data and assumed a high-end of 8 hours because the surrogate data or modeled values are 8-hour TWA
values. EPA assumed a mid-range of 4 hours for central tendency exposure duration. The
representativeness of the assumed estimates of duration of inhalation and dermal exposure for the
assessed activities toward the true di stribution of duration for all worker activities in this occupational
exposure scenario is uncertain. Skin surface areas for actual dermal contact are uncertain. EPA did not
find data on the use of ulo\ es lor this occupational exposure scenario and assumed glove usage with
minimal to no employee training or no glove usage due to the wide-spread use of paint, coating,
adhesi\ e. and sealant products The assumed glove protection factor values are uncertain.
The available monitoring data for spray application is from 1996 and the surrogate monitoring data used
in the model for roll ' curtain application is from 1994 or earlier. The extent to which these data are
representative of current worker inhalation exposure potential is uncertain. The worker activities
associated with the surrogate data (surrogate work activities using NMP) used to assess worker
inhalation exposure during dip application are not detailed for all sample points. The modeled inhalation
exposure concentration during roller / brush application was obtained from RIVM (2013) and not
generated by EPA. For all occupational exposure scenarios, representativeness of the monitoring data,
surrogate monitoring data, or modeled data toward the true distribution of inhalation concentrations for
this occupational exposure scenario is uncertain.
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Overall Confidence
Considering the overall strengths and limitations, the overall confidence of the PBPK input parameters
for this occupational exposure scenario is medium.
2.4.1.2.8 Electronic Parts Manufacturing
This scenario includes the use of NMP in the electronics industry. For this industrial exposure scenario,
EPA assessed inhalation, vapor-through-skin, and dermal exposures to NMP from the following
exposure scenarios during semiconductor manufacturing:
• Container handling (small containers);
• Container handling (drums);
• Workers in the fabrication shop;
• Maintenance activities;
• Virgin NMP truck unloading; and
• Waste NMP truck loading.
EPA expects that these activities present the largest range of potential exposures lor use of NMP in the
semiconductor manufacturing industry. While operations for the various types of electronics
manufacturing that are included in this occupational exposure scenario may vary, EPA expects these
activities in the semiconductor manufacturing industry are representative of the operating conditions
expected at other electronic parts manufacturing facilities, due lo llic use of similarly controlled
operations.
Inhalation and Vayor-through-Skin
Electronic parts manufacturing covers the use of WIP for lithium ion battery manufacturing, cleaning of
electronic parts, coating of electronic parts, including magnet wire coatings, and photoresist and solder
mask stripping. However. F.PA only found inhalation monitoring data for the use of NMP in
semiconductor manufacturing. Specifically, EPA uses data received from the Semiconductor Industry
Association (SIA), which include full-shift personal breathing zone sampling results at semiconductor
fabrication facilities during container handling of both small containers and drums, workers inside the
fabrication rooms, maintenance workers, workers that unload trucks containing virgin NMP (100%), and
workers that load trucks with liquid waste NMP (92%) (MA. 2019).
The SI A monitoring data were summarized into the PBPK modeling full-shift input parameters in Table
2-31. The majority (96% of all samples) of samples in SIA (2019) were non-detect for NMP. Because
the geometric standard deviation of the data set is greater than three, EPA used the limit of detection
(LOD) divided In two to calculate central tendency and high-end values where samples were non-detect
for NMP ( ). Due to the high amount of non-detect results, this method may result in
bias. This is furthei described in the supplemental document Risk Evaluation for N-Me thy Ipyrrolidone
(2-Pyrrolidinone, 1 Methyl-) (NMP), Supplemental Information on Occupational Exposure Assessment
(I J019r). The SIA data included samples of both 8-hour TWA and 12-hour TWA values, with
much of the data being 12-hour TWA. EPA used the 12-hour TWA values to assess occupational
exposures in this occupational exposure scenario, as there is more data available for this exposure
duration, indicating that typical shifts in this industry are 12 hours. Note, however, that the single data
points available for the last two tasks in Table 2-31 are 8-hour TWA values.
Confidential data were submitted for an additional scenario for this industry and are not included in this
evaluation.
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Table 2-31. Summary of Parameters for PBPK Modeling of Worker Inhalation Exposure During
Electronic Parts Manufacturing
lull-Shift NMP
Duralion-liascri
Work
Activity 11
Parameter
( haraclcrizalion
Air
Concentration
NMP Air
Concentration
Source
Data
Quality
(mg/nr\ 12-hour
TWA)
(nig/in')
Rating
Container
handling, small
containers
Central tendency
(50th percentile)
0.507
No data
High-end (95th
percentile)
0.608
No data
Container
Central tendency
(50th percentile)
0.013
No data
handling, drums
High-end (95th
percentile)
1.54
No data
Fab worker
Central tendency
(50th percentile)
0.138
No data
(SIA.
High
High-end (95th
percentile)
0.405
No data
:0h>)
Maintenance
Central tendency
(50th percentile)
0.020
No data
High-end (95th
percentile)
0.690
No data
Virgin NMP
truck unloading
Single value
4.78 b
No data
Waste truck
loading
Single value
0.709 b
No data
a Electronic parts maniil'acliiriim includes the use of NMP for battery manufacturing, cleaning of electronic parts, coating of
electronic parts, including mamicl u ire cualnms. and photoresist and solder mask stripping.
b These arc 8-hour TW \ \ allies
DermaI
Table 2-32 summarizes the parameters used to assess dermal exposure during use of NMP in in the
electronics industries Most of these parameters were determined based on assumptions described in
Section 2.4.1.1. EPA used data from SIA (2.019). public comments, literature, and the Use and Market
Profile for N-Metfn Ipyrro/n/otie ( bt. 2017) to determine the NMP weight fraction. The underlying data
has a data quality rating of high. Because this scenario has only industrial sites, EPA assumes that
workers are likely to wear protective gloves and have basic training on the proper usage of these gloves
for both central and high-end exposures, corresponding to a protection factor of 10.
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Table 2-32. Summary of Parameters for Worker Dermal Exposure During Electronic Parts
Manufacturing
Work Activity
il
Parameter
Characterization
(ilove
Protection
l'"actor(s)
NMP
Weight
l-'raction
Skin
Surface
Area
Kxposed h
Kxposure
Duration
liotly
Weight
h
I nitless
cm2
lir/dav
Ivli
Container
handling, small
containers
Central Tendency
10
0.6
445 (f)
535 (m)
6
74 (f)
88 (m)
High-End
10
0.75
890 (f)
1,070 (m)
12
Container
handling,
drums
Central Tendency
10
0.5
445 (f)
535 (m)
6
74 (f)
88 (m)
High-End
10
0.75
890 (f)
1,070 (m)
12
Fab worker
Central Tendency
10
0.15
445 (f)
535 (m)
6
74 (f)
88 (m)
High-End
10
0.999
890 (f)
1,070 (m)
12
Maintenance
Central Tendency
10
0.55
445 (f)
535 (m)
6
74 (f)
88 (m)
High-End
10
1
890 (f)
1,070 (m)
12
Virgin NMP
truck unloading
Central Tendency
10
1
445 (f)
535 (m)
4
74 (f)
88 (m)
High-End
10
1
890 (f)
1,070 (m)
8
Waste truck
loading
Central Tendency
10
0.92
445 (f)
535 (m)
4
74 (f)
88 (m)
High-End
10
0.92
890 (f)
1,070 (m)
8
" Electronic parts manufacturing includes the use of NMP for battery manufacturing, cleaning of electronic parts, coating of
electronic parts, including magnet wire coatings, and photoresist and solder mask stripping.
b EPA assessed these exposure factors for both females and males. Values associated with females are denoted with (f) and
values associated with males are denoted with (m).
PBPK Inputs
EPA assessed PBPK parameters for central tendency and high-end exposure scenarios based on the
characterizations listed in Table 2-33.
The numeric parameters corresponding to the characterizations presented in Table 2-33 are summarized
in Table 2-34. These are the inputs used in the PBPK model.
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2118
2119
Table 2-33. Characterization of PBPK Model Input Parameters for Electronic Parts
Scenario
Work
Activity
;i
Air
Concentration
Data
Characterization
h
Kxposurc
Duration
Skin
Surface
Area
Kxposed
(•loves
NMP W eight
l-'raction
Characterization
Central
Tendency
All
activities
Central tendency
(50th percentile)
Mid-point of
shift duration
1-hand
Yes
Central tendency
High-end
All
activities
High-end (95th
percentile)
High-end of
shift duration
2-hand
Yes
High-end
a Electronic parts manufacturing includes the use of NMP for battery manufacturing, cleaning of electronic parts, coating of
electronic parts, including magnet wire coatings, and photoresist and solder mask stripping.
bOnly a single estimate was available for virgin NMP truck unloadnm and waste truck loading. This snide air concentration
value was used with both central tendency and high-end duialimi and dermal parameters.
Work
Activity
Scenario
Duration-
liased NMP
Air
Concenlratio
n (nig/nr')
Kxposurc
Duration
(hi)
Skin
Surface
Area
Kxposed
(cm2)11 h
(•loves
Protection
Kactor
NMP
Weight
l-'raction
liody
Weigh
t (kg)11
Container
handling,
small
containers
Central
Tendency
1.01
6
445(f)
5.i5 (m)
10
0.6
74 (f)
88 (m)
High-end
1) OOS
12
89i) (f)
1,070 (m)
10
0.75
74 (f)
88 (m)
Container
handling,
drums
Central
Tendency
o o:o
6
445 (f)
535 (m)
10
0.5
74 (f)
88 (m)
TTiuli-cnd
1 54
12
890 (f)
1,070 (m)
10
0.75
74 (f)
88 (m)
Fall \\ orker
Central
Tendency
o 270
6
445 (f)
535 (m)
10
0.15
74 (f)
88 (m)
1 [igh-end
i)405
12
890 (f)
1,070 (m)
10
0.999
74 (f)
88 (m)
Maintenanc
e
Central
Tendency
i) 040
6
445 (f)
535 (m)
10
0.55
74 (f)
88 (m)
1 liuh-end
i) 690
12
890 (f)
1,070 (m)
10
1
74 (f)
88 (m)
Virgin NMP
truck
unloading
Central
tendency
9.56
4
445 (f)
535 (m)
10
1
74 (f)
88 (m)
High-end
4.78
8
890 (f)
1,070 (m)
10
1
74 (f)
88 (m)
Waste truck
loading
Central
tendency
1.42
4
445 (f)
535 (m)
10
0.92
74 (f)
88 (m)
High-end
0.709
8
890 (f)
1,070 (m)
10
0.92
74 (f)
88 (m)
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Work
Activity
Sccnsirio
Duration-
lisiscd NMP
Air
Conccnlralio
n (nig/nr')
Kxposure
Duration
(l»)
Skin
Surface
Area
Kxposed
(cur)"h
(•loves
Protection
l-actor
NMP
Weight
fraction
liotly
Weigh
t (kg)11
" EPA assessed these exposure factors for both females and males. Values associated with females are denoted with (f) and
values associated with males are denoted with (m).
bEPA assessed a skin surface area exposed to liquid NMP of 0.1 cm2for ONUs fur each scenario. However, EPA did not
assess glove usage (protection factor = 1) for ONUs.
Summary
In summary, dermal and inhalation exposures are expected for this use N\\ has not identified
additional uncertainties for this use beyond those included in Section 2.4.1.4. I -PA identified primary
strengths and limitations and assigned an overall confidence to the occupational exposure scenario
inputs to the PBPK model, as discussed below. EPA considered the assessment approach, the quality of
the data, and uncertainties to determine the level of confidence. Note that the effects of the limitations
on this assessment are discussed in Section 2.4.1.4.
Primary Strengths
EPA assessed dermal exposure to central tendency and high-end Wll' weight fractions, calculated as
the 50th and 95th percentiles, respectively, from the data provided by S1A ( .; i ;>), which has a data
quality rating of high. EPA used directly applicable inhalation monitoring data, which is the highest of
the approach hierarchy, to estimate worker inhalation exposure during a variety of semiconductor
manufacturing tasks. These data include over one hundred data points and have a data quality rating of
high.
Primary Limitations
The SIA (2.019) monitoring data were pro\ ided as 8-hour or 12-hour TWA values. EPA assumed 8 or 12
hours as the high-end exposure duration and mid-range of 4 or 6 hours as the central tendency exposure
duration. The representati\ eness of the estimates (if duration of inhalation and dermal exposure for the
assessed activities toward the true distribution of duration for all worker activities in this occupational
exposure scenario beyond semiconductor manufacturing is uncertain. Skin surface areas for actual
dermal contact are uncertain. EPA did not find data on the use of gloves for this occupational exposure
scenario and assumed glove usage is likely based on professional judgment, due to the highly controlled
nature of electronics manufacturing. The assumed glove protection factor values are uncertain.
The majority of the data points in SIA (2019) were non-detect for NMP and, for these samples, EPA
used the LOD/2 to calculate central tendency and high-end inhalation exposure concentration values.
Due to the high amount of non-detect results, this method may result in bias. The representativeness of
the monitoring data for semiconductor manufacturing toward the true distribution of inhalation
concentrations for all worker activities in this occupational exposure scenario is uncertain.
Overall Confidence
Considering the overall strengths and limitations, the overall confidence of the PBPK input parameters
for this occupational exposure scenario is medium.
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2.4.1.2.9 Printing and Writing
This scenario includes printing and writing with inks containing NMP. For this industrial and
commercial exposure scenario, EPA assessed inhalation, vapor-through-skin, and dermal exposures to
inks containing NMP during printing activities. Additionally, EPA assessed dermal exposures to inks
containing NMP during writing activities.
While EPA does expect that workers may perform additional activities during this scenario, such as
unloading or maintenance activities, EPA expects that printing and u riling activities present the largest
range of potential exposures.
Inhalation and Vayor-throush-Skin
EPA did not find inhalation monitoring data for the use of NMP-based pi inlinu inks. For printing
activities, EPA used ink mist concentration data from a NIOSH Health Hazard \ .\ aluation at a
newspaper printing shop, with assumed NMP concentrations, to assess potential inhalation exposures in
this occupational exposure scenario. Of the available data, this surrogate data has the highest quality;
thus, EPA used this data to assess exposure for this use.
EPA did not find inhalation monitoring data for the use of u riling utensils containing NMP. EPA did not
assess potential inhalation exposures during the use of lNMP-based u riling inks based on information
indicating these exposures may be negligible from a N1CNAS assessment (ICNAS. 2016) and the
likely outdoor use of the one writing product thai was identified (weather-resistant marker).
The monitoring data presented in Table 2-35 represent input parameters used for the PBPK modeling.
The supplemental document Risk Evaluation for N-Methylpyrrolidone (2-Pyrrolidinone, 1 Methyl-)
(NMP), Supplemental Injormation on (hx upationa! Exposure Assessment ( )19r) provides
additional details.
Table 2-35. Summary of Parameters for PBPK Modeling of Worker Inhalation Exposure During
Printing and Writing
Work
Activity
Parameter
( haracleri/alion
lull-Shift NMP
Air
Concent rat ion
Duration-liascd
NMP Air
Concentration
Source
Data
Quality
Rating
(ing/m\ 8-hr
TWA)
(ing/nr')
Printing
Central tendency
(5<)lh percentile)
0.018
0.016 (duration = 4
hr)
(Belanger
and Cove.
1983)
Medium
1 ligh-end (95th
percentile!
0.172
0.042 (duration = 4
hr)
Writing
Not assessed
Dermal
Table 2-36 summarizes the parameters used to assess dermal exposure during printing and writing
activities. Most of these parameters were determined based on assumptions described in Section 2.4.1.1.
EPA used data from public comments and the Use and Market Profile for N-Methylpyrrolidone (Abt
2.017) to determine the NMP weight fraction. The underlying data have a data quality rating of high.
Because writing inks are contained within markers and pens, EPA expects the surface area of skin
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potentially exposed to NMP to be smaller than the surface area of one or two hands. EPA used data from
Australian Government Department of Health (2016). which has a data quality rating of medium, for the
skin surface area exposed during writing. Because this scenario covers a variety of commercial and
industrial sites, EPA assumes that either no gloves are used or, if gloves are used, there is no permeation
data to indicate the glove material is protective for NMP, corresponding to a protection factor of 1. EPA
assesses a central tendency scenario assuming the use of gloves with minimal to no employee training,
corresponding to a protection factor of 5.
Table 2-36. Summary of Parameters for Worker Dermal Exposure to l.iquids During Printing
and Writing
Work
Activity
Parameter
Characterization
Clove
Protection
Kactor(s)
NMP
W eight
Kraction
Skin
Surface
Area
Kx posed 11
Kxposurc
Duration
liodv
W'eight
;i
In it less
cm2
lir/dav
Printing
Central Tendency
5
0.05
445 (f)
535 (m)
4
74 (f)
88 (m)
High-End
1
0.07
S^i(l)
I.D7D (m)
8
Writing
Central Tendency
5
o.l
1 b
0.5
74 (f)
88 (m)
High-End
i
i) 2
1 b
0.5
a EPA assessed these exposure factors for both females and males Values associated w iill females are denoted with (f) and
values associated with males are denoted with (m).
b This surface area was assumed for bolli males and females hased on (Ml 16).
PBPK Inputs
EPA assessed PBPK parameters lor central tendency and high-end exposure scenarios based on the
characterizations listed in TaMe 2-37
The numeric parameters corresponding to the characterizations presented in Table 2-37 are summarized
in TuMe 2-3S These are the inputs used in the PBPK model.
Table 2-37. Characterization of PUI'K Model Input Parameters for Printing and Writing
Scenario
Work
Activity
Air Concentration
Data
Characterization
Kxposurc
Duration
Skin
Surface
Area
Kxposed
(cm2)
(•loves
NMP Weight
Kraction
Characterization
Central
Tendency
Printing
Central tendency
(50th percentile)
Based on
4-hr TWA
data
1-hand
Yes
Central tendency
High-end
Printing
High-end (95th
percentile)
Based on
8-hr TWA
data
2-hand
No
High-end
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Scenario
Work
Activity
Air Concentration
Data
Characterization
Kxposure
Duration
Skin
Surface
Area
Kxposed
(cm2)
Gloves
NMP Weight
l-'raction
Characterization
Central
Tendency
Writing
Inhalation exposure
not assessed
Based on
one contact
event
1 cm2
Yes
Central tendency
High-end
Writing
Inhalation exposure
not assessed
Based on
one contact
event
1 enr
No
High-end
Table 2-38. PBPK Model Input Parameters for Printing suit! Writing
Scenario
Work
Activity
Duralion-liascd
NMP Air
Concentration
(nig/m')
Kxposurc
Duration
(hr)
Skin
Surface
Area
Kxposed
(cm2) "¦h
Cloves
Protection
Kaclor
NMP
W eight
Traction
liodv
W eight
(kg)"
Central
Tendency
Printing
0.016
4
445 (f)
535 (m)
5
0.05
74 (f)
88 (m)
High-end
Printing
0.172
S
XW (f)
l.i)7o(m)
1
0.07
74 (f)
88 (m)
Central
Tendency
Writing
0
i) 5
1
5
0.1
74 (f)
88 (m)
High-end
Writing
t)
0.5
1
1
0.2
74 (f)
88 (m)
a EPA assessed these exposure factors I'm' hotli females and males. Values associated with females are denoted with (f) and
values associated with males arc denoted \\ uli (m).
bEPA assessed a skin surface area exposed lo liquid WIP of t) 1 cur for ONUs for each scenario. However, EPA did not
assess glo\e usaue (protection factor 1) for( )\l s
Summary
In summary, dermal and inhalation exposures are expected for use ofNMP in printing. Only dermal
exposure is expected lor use of WIP in u riting activities. EPA has not identified additional
uncertainties lor this use beyond those included in Section 2.4.1.4. EPA identified primary strengths and
limitations and assigned an overall confidence to the occupational exposure scenario inputs to the PBPK
model, as discussed below EPA considered the assessment approach, the quality of the data, and
uncertainties to determine the level of confidence. Note that the effects of the limitations on this
assessment are discussed in Section 2.4.1.4.
Primary Strengths
For printing activities, EPA assessed dermal exposure to central tendency and high-end NMP weight
fractions, calculated as the 50th and 95th percentiles, respectively, from a variety of data sources with
data quality ratings of high. For writing activities, EPA assessed dermal exposure to 10 to 20% NMP
based on one writing product identified in the Use and Market Profile for N-Methylpyrrolidone (Abt.
2017). For worker dermal exposure during writing, EPA determined the skin surface area derm ally
exposed to writing ink using a literature source with a data quality rating of high. To estimate worker
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inhalation exposure during printing, EPA used surrogate monitoring data, which is in the middle of the
approach hierarchy. These data include 48 samples and have a data quality rating of high. EPA used
durations associated with inhalation monitoring data to estimate duration of inhalation and dermal
exposure during printing activities.
Primary Limitations
For writing, EPA did not find exposure duration data and assumed a high-end of 8 hours based on the
length of a full shift and a central tendency of 4 hours based on the mid-range of a shift. The
representativeness of the assumed estimates of duration of inhalation and dermal exposure for the
assessed printing and writing activities toward the true distribution of duration for all worker activities in
this occupational exposure scenario is uncertain. For printing, skin surface areas for actual dermal
contact are uncertain. EPA did not find data on glove usage. For printing acli\ ities. EPA assumed glove
usage with minimal to no employee training or no glove usage due to the wide-spread use of ink
products. The assumed glove protection factor values are uncertain. For writing acti\ ilies, EPA assumed
glove usage is unlikely for the use of markers based on professional judgment. The surrogate monitoring
data used to estimate occupational inhalation exposure din ing printing is from 1983. The extent to which
these data are representative of current worker inhalation exposure potential is uncertain. The
representativeness of the surrogate monitoring data toward the true distribution of inhalation
concentrations for this occupational exposure scenario is uncertain
Overall Confidence
Considering the overall strengths and limitations, the o\ erall confidence of the PBPK input parameters
for this occupational exposure scenario is medium.
2.4.1.2.10 Soldering
This scenario includes soldering with solder materials containing NMP. For this industrial and
commercial exposure scenario. N\\ assessed dermal exposures to NMP during soldering.
While EPA does expect that workers may perform additional activities during this scenario, such as
equipment maintenance activities, F.PA expects that soldering presents the largest range of potential
exposures.
Inhalation and I apor-throHuh-Skin
Due to the low WTP content in the one identified soldering production containing NMP (1 to 2.5 weight
percent NMP), the potential for worker inhalation exposures is likely small. In addition, some of the
NMP may be destroyed in the soldering process, further mitigating the potential for inhalation
exposures. EPA therefore did not assess inhalation and vapor-through-skin exposures for this
occupational exposure scenario.
Dermal
Table 2-39 summarizes the parameters used to assess dermal exposure during the use of soldering
products containing NMP. Most of these parameters were determined based on assumptions described in
Section 2.4.1.1. EPA used data from the Use and Market Profile for N-Methylpyrrolidone (Abt 2017) to
determine the NMP weight fraction. Because this scenario covers a variety of commercial and industrial
sites, EPA assumes that either no gloves are used or, if gloves are used, there is no permeation data to
indicate the glove material is protective for NMP, corresponding to a protection factor of 1. EPA
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assesses a central tendency scenario assuming the use of gloves with minimal to no employee training,
due to the widespread nature of this occupational exposure scenario, corresponding to a protection factor
of 5.
Table 2-39. Summary of Parameters for Worker Dermal Exposure During
Soldering
Work
Parameter
(Jove
Protection
l'"actor(s)
YMP
W eight
Skin
Surface
Area
V.x posed 11
Kxposurc
Duration
liody
\Y'eight
Activity
Characterization
l-'raction
;i
In it less
cm2
lir/dav
kg
Soldering
Central Tendency
5
0.01
445(f)
535 (in)
4
74 (f)
High-end
1
0.025
890 (f)
1,070 (m)
S
88 (m)
a EPA assessed these exposure factors for both females and males. Values associated with females* arc denoted \\ 111i (f) and
values associated with males are denoted with (m).
PBPK Inputs
EPA assessed PBPK parameters for central tendency and high-end exposure scenarios based on the
characterizations listed in Table 2-40.
The numeric parameters corresponding to the chaiacleii/.alions presented in Table 2-40 are summarized
in Table 2-41. These are the inputs used in the PlJI'k model
Table 2-40. Characterization of 1'iiPK Model Input Parameters for Soldering
Scenario
Work
Activity
Air Concentration
Data
Characterization
Kxposurc
Duration
Skin
Surface
Area
Ivxposed
(•loves
YM P W eight
l-'raction
Characterization
Central
Tendency
Soldering
Inhalation
l-\|")osiiie Not
Assessed
Assumed
4 hours
1-hand
Yes
Central Tendency
High-end
Soldering
Inhalation
l-\posure Not
Assessed
Assumed
8 hours
2-hand
No
High-end
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Table 2-41. PBPK Model Input Parameters for Soldering
Scenario
Duralion-liascd
NMP Air
Concentration
(nig/nr')
Kxposure
Duration
(M
Skin Surface
Area
Kxposed
(cm2)11 h
(•loves
Protection
Kactor
NMP
Weight
l-'raction
liodv
Weight
(kg)"
Central
Tendency
0
4
445 (f)
535 (m)
5
0.01
74 (f)
88 (m)
High-end
0
8
890 (f)
1,070 (m)
1
0.025
74 (f)
88 (m)
a EPA assessed these exposure factors for both females and males. Values asMviaial \\ nli tannics are denoted with (f) and
values associated with males are denoted with (m).
bEPA assessed a skin surface area exposed to liquid NMP of 0.1 cm2 for ONUs for each scenario 1 lowcvcr. EPA did not
assess glove usage (protection factor = 1) for ONUs.
Summary
In summary, only dermal exposure is expected for this use I-PA has not identified additional
uncertainties for this use beyond those included in Section 2 4 1.4. EPA identified primary strengths and
limitations and assigned an overall confidence to the occupational exposure scenario inputs to the PBPK
model, as discussed below. EPA considered the assessment approach, the quality of the data, and
uncertainties to determine the level of confidence Note thai the effects of (he limitations on this
assessment are discussed in Section 2.4.1.4.
Primary Strengths
EPA assessed worker dermal exposure to 1 - 2.5% NMP based on one soldering product identified in
the Use and Market Profile Jor S-\ lelhylpyrrolidone ( h "1017). EPA did not assess occupational
inhalation exposure because most NMP may be destroyed in the soldering process, mitigating the
potential for significant inhalation exposures
Primary I imiiaiions
EPA did not find exposure duration data and assumed a high-end of 8 hours based on the length of a full
shift and a central tendency of 4 hours based on the mid-range of a shift. The representativeness of the
assumed estimates of duration of inhalation and dermal exposure toward the true distribution of duration
for all worker activities in this occupational exposure scenario is uncertain. Skin surface areas for actual
dermal contact are uncertain. EPA did not find data on the use of gloves for this occupational exposure
scenario and assumed ulove usage with minimal to no employee training or no glove usage due to the
commercial nature of this use. The assumed glove protection factor values are uncertain.
Overall Confidence
Considering the overall strengths and limitations, the overall confidence of the PBPK input parameters
for this occupational exposure scenario is low to medium.
2.4.1.2.11 Commercial Automotive Servicing
This scenario includes automotive servicing with products containing NMP. For this commercial
exposure scenario, EPA assessed inhalation, vapor-through-skin, and dermal exposures to products
containing NMP during aerosol degreasing of automotive brakes.
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While EPA does expect that workers may perform additional activities during this scenario, such as
unloading or sampling, EPA expects that aerosol degreasing activities present the largest range of
potential exposures.
Inhalation and Vayor-through-Skin
EPA did not find monitoring data for the use of NMP products during automotive servicing. Because
EPA did not find relevant monitoring data for this use in the published literature, modeling estimates
were used to assess exposure for this use, as described below.
In lieu of monitoring data, EPA modeled potential occupational inhalation exposures for workers using
EPA's model for Occupational Exposures during Aerosol Degreasing of Automotive Brakes. The
Occupational Exposures during Aerosol Degreasing of Automotive Brakes Model in \ ol\ es probabilistic
modeling. This model uses a near-field/far-field approach, where an aerosol application located inside
the near-field generates a mist of droplets, and indoor air movements lead to the coin eel ion of the
droplets between the near-field and far-field. Workers are assumed to be exposed lo NMP droplet
concentrations in the near-field, while ONUs are exposed al concentrations in the far-field. Consistent
with the approach for other OESs, EPA uses the central tendency worker air concentration to evaluate
ONU exposure and further refines this estimate using far-field modeling or applicable area monitoring
data if the ONU MOE was below the benchmark MOE. Refinement was not necessary for this OES
since the ONU MOE was above the benchmark MOI- The supplemental document Risk Evaluation for
N-Methylpyrrolidone (2-Pyrrolidinone, 1 Meihyl-i f.\Ml'). Supplemental Information on Occupational
Exposure Assessment ( 2019r) includes background information on this model, including
model results and EPA's rationale for using it
Table 2-42. Summary of Parameters for PliPK Modeling of W orker Inhalation Exposure During
Commercial Automotive Servicing
Work
Activity
Parameter
Characterization
lull-Shift
NMP Air
Concentration
Duration-
liased NMP
Air
Concent rat ion
Source
Data
Quality
Rating
(nig/nr\ 8-hr
TWA)
(nig/nr*)
Aerosol
Degreasing
Central tendency
(50th percentile)
(v39
19.96 (duration
= 1 hr)
Occupational
Exposures
during Aerosol
Degreasing of
Automotive
Brakes Model
Not
applicable11
1 liuh-end (l>5lh
percentile)
43.4
128.8 (duration
= 1 hr)
a - EPA models are standard sources used by EPA for occupational exposure assessments. EPA did not systematically
review models that were developed by EPA.
Dermal
Table 2-43 summarizes the parameters used to assess dermal exposure during cleaning activities. Most
of these parameters were determined based on assumptions described in Section 2.4.1.1. EPA used data
from public comments and the Use and Market Profile for N-Methylpyrrolidone (Abt. 2017) to
determine the NMP weight fraction. The underlying data have a data quality rating of high. Because this
scenario covers a variety of commercial and industrial sites, EPA assumes that either no gloves are used
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or, if gloves are used, there is no permeation data to indicate the glove material is protective for NMP,
corresponding to a protection factor of 1. EPA assesses a central tendency scenario assuming the use of
gloves with minimal to no employee training, corresponding to a protection factor of 5.
Table 2-43. Summary of Parameters for Worker Dermal Exposure to Liquids During Commercial
Automotive Servicing
Work
Activity
Parameter
Characterization
(Jove
Protection
l-"actor(s)
NMP
\Y'eight
Kraction
Skin
Surface
Area
Kxposed "
Kxposure
Duration
liody
W eight
il
In it loss
cm2
lir/dav
ks
Commercial
Automotive
Servicing
Central Tendency
5
i) 025
445 (f)
535 (in)
1
74 (1)
High-end
1
<) 33
S90 (f)
1.070 (m)
S
88 (m)
aEPA assessed these exposure factors for both females and males Values associated with females are denoted with (f) and
values associated with males are denoted with (m).
PBPK Inputs
EPA assessed PBPK parameters for central tendency and high-end exposure scenarios based on the
characterizations listed in Table 2-44.
The numeric parameters corresponding to the characterizations presented in Table 2-44 are summarized
in Table 2-45. These are the inputs used in the PBPK model.
Table 2-44. Characterization of PIJPK Model Input Parameters for Commercial Automotive
Servicing
Scenario
Work
Activity
Air Concentration
Data
Characterization
Kxposure
Duration
Skin
Surface
Area
Kxposed
(•loves
NMP Weight
l-'raction
Characterization
Central
Tendency
Aerosol
decreasing
Central tendency
(5<)lh percentile)
Based on
time for
one job
1-hand
Yes
Central Tendency
High-end
Aerosol
decreasing
1 liuli-end (95th
percentile)
Assumed
8 hours
2-hand
No
High-end
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Table 2-45. PBPK Model Input Parameters for Commercial Automotive Servicing
Scenario
Work
Activity
Duralion-liascd
NMP Air
Concentration
(nig/nr')
Kxposure
Duration
(lir)
Skin
Surface
Area
Kxposed
(cm2)11 h
(•loves
Protection
l-'actor
NMP
\Y'eight
l-'raction
liody
\Y'eight
(kg)"
Central
Tendency
Aerosol
degreasing
19.96
1
445 (f)
535 (m)
5
0.025
74 (f)
88 (m)
High-end
Aerosol
degreasing
43.4
8
890 (f)
1,070 (m)
1
0.33
74 (f)
88 (m)
a EPA assessed these exposure factors for both females and males. Values associated \\ nli females are denoted with (f) and
values associated with males are denoted with (m).
bEPA assessed a skin surface area exposed to liquid NMP of 0.1 cm2 for ONUs for each scenario 1 lowever, EPA did not
assess glove usage (protection factor = 1) for ONUs.
Summary
In summary, dermal and inhalation exposures are expected for this use EPA has not identified
additional uncertainties for this use beyond those included in Section 2 4.1.4. EPA identified primary
strengths and limitations and assigned an overall confidence to the occupational exposure scenario
inputs to the PBPK model, as discussed below EPA considered the assessment approach, the quality of
the data, and uncertainties to determine the lc\ el of confidence Note that the effects of the limitations
on this assessment are discussed in Section 2 4 14.
Primary Strengths
EPA assessed dermal exposure to central tendency and high-end \ VIP weight fractions, calculated as
the 50th and 95th percentiles, respect i\ ely, from a variety of data sources with data quality ratings of
high. Modeling, in the middle of the approach hierarchy, was used to estimate occupational inhalation
exposure concentrations. For modeling of these air concentrations, EPA attempted to address variability
in input parameters by estimating both central tendency and high-end parameter values. Additionally,
EPA used Monte Carlo simulation to capture \ a liability in input parameters. EPA expects the duration
of inhalation and dermal exposure to be realistic, as the duration is based on the length of time to
conduct aerosol degreasing of automoti\e brakes.
Primary I imitations
The represeniaii\ eness of the estimates of duration of inhalation and dermal exposure for the aerosol
brake degreasinu activities toward the true distribution of duration for all worker activities in this
occupational exposure scenario is uncertain. Skin surface areas for actual dermal contact are uncertain.
EPA did not find data on the use of gloves for this occupational exposure scenario and assumed glove
usage with minimal to no employee training or no glove usage due to the wide-spread use of degreasing
products. The assumed glove protection factor values are uncertain. For the modeling of NMP air
concentrations, EPA used aerosol product use rate and application frequency from one literature source
(GARB. 2.000) on brake servicing. The extent to which this is representative of other aerosol degreasing
applications involving NMP is uncertain. The representativeness of the modeling results toward the true
distribution of inhalation concentrations for this occupational exposure scenario is uncertain.
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Overall Confidence
Considering the overall strengths and limitations, the overall confidence of the PBPK input parameters
for this occupational exposure scenario is medium.
2.4.1.2.12 Laboratory Use
This scenario includes the use of NMP in a laboratory setting. For this industrial and commercial
exposure scenario, EPA assessed inhalation, vapor-through-skin, and dermal exposures to 100% NMP
during laboratory activities.
While EPA does expect that workers may perform additional acli\ ilics during this scenario, such as
unloading, EPA expects that laboratory use activities present the largest range of potential exposures.
Inhalation and Vayor-through-Skin
EPA only found one data source that had inhalation monitoring data, representing the preparation of
NMP for use in samples, sample preparation involving the dissolving of solids in NMP. and sample
analysis. These data were used as input into the PBPK model lor 2-hour exposure duration. EPA did not
find additional monitoring data, thus used a modeled exposure lor the use of NMP in a laboratory setting
for the full-shift concentrations. As the quality of both the monitoring and modeled data is acceptable,
EPA used all available data to assess this occupational exposure scenario
The monitoring data and modeled exposure summarized in Table 2-4(-> are the input parameters used for
the PBPK modeling. The supplemental document Risk I.valuationJor N-Methylpyrrolidone (2-
Pyrrolidinone, 1 Methyl-) (NMP), Supplemental Injorniaiion on (kcii/HiiionalExposure Assessment
(U.S. EPA. 2019r) pro\ ides additional details.
Table 2-46. Summary of Parameters for PBPK Modeling of Worker Inhalation Exposure During
Laboratory Use
lull-Shift NMP
Duration-liascri
Work
Activity
Parameter
( haracteri/ation
Air
Concentration
NMP Air
Concentration
Source
Data
Qualitv
(ing/m\, 8-hr
TWA)
(nig/nr')
Rating
Central tendency
(unknown statistical
2.07
0.200 (duration =
2 hr)
(Solomon
et al„
Medium
Laboratory
characterization)
1996)
Use
1 ligh-end (unknown
statistical
4.13
No data
CRIVM,
2013)
High
characterization)
Dermal
Table 2-47 summarizes the parameters used to assess dermal exposure during use of NMP in
laboratories. Most of these parameters were determined based on assumptions described in Section
2.4.1.1. Because NMP is used as a carrier chemical, EPA expects that NMP may be used in pure form
(i.e., 100 percent NMP). Because laboratories have procedures and trainings to ensure accuracy and
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quality of the performed analyses, EPA assumes that workers are likely to wear protective gloves and
have basic training on the proper usage of these gloves, corresponding to a protection factor of 10.
Table 2-47. Summary of Parameters for Worker Dermal Exposure During Laboratory Use
Work
Activity
Parameter
Characterization
(Jove
Protection
l'"actor(s)
YMP
Weight
l-'raction
Skin
Surface
Area
Kxposed "
Kxposure
Duration
liody
Weight
il
In it less
cm2
lir/dav
kg
Laboratory
Use
Central tendency
10
1
445(f)
535 (in)
2
74 (f)
88 (m)
High-end
10
1
890 (f)
1,070 (m)
S
a EPA assessed these exposure factors for both females and males Values associated with females are denoted with (f) and
values associated with males are denoted with (m).
PBPK Inputs
EPA assessed PBPK parameters for central tendency and high-end exposure scenarios based on the
characterizations listed in Table 2-48.
The numeric parameters corresponding to 1he characterizations presented in Table 2-48 are summarized
in Table 2-49. These are the inputs used in the IMiPK model
Table 2-48. Characterization of PBPK Model Input Parameters by Laboratory Use
Scenario
Work
Activity
Air Concentration
Data
Characterization
Kxposurc
Duration
Skin
Surface
Area
Kxposed
(•loves
YM P W eight
l-'raction
Characterization
Central
Tendency
1 .abomlory
acli\ ilies
Ceniml tendency
(iinknou n
statistical
characterization)
liased on
2-hr TWA
data
1-hand
Yes
N/A - 100% is
assumed for both
exposure scenarios
High-end
Laboratory
acli \ i lies
1 liuh-end
(unknown
statistical
characterization)
Assumed
8 hours
2-hand
Yes
N/A - 100% is
assumed for both
exposure scenarios
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Table 2-49. PBPK Model Input Parameters for Laboratory Use
Scenario
Duration-Based
NMP Air
Concentration
(nig/nr')
Kxposure
Duration
(In)
Skin
Surface
Area
Kxposed
(cm2)"h
(•loves
Protection
l-actor
NMP
Weight
l-'raction
IJodv
Weight
(kg)11
Central
Tendency
0.200
2
445 (f)
535 (m)
2t)
1
74 (f)
88 (m)
High-end
4.13
8
890 (f)
1,070 (m)
2<)
1
74 (f)
88 (m)
a EPA assessed these exposure factors for both females and males. Values assoaaied \\ nli females are denoted with (f) and
values associated with males are denoted with (m).
bEPA assessed a skin surface area exposed to liquid NMP of 0.1 cm2 for ONUs for each scenario 1 low e\ er, EPA did not
assess glove usage (protection factor = 1) for ONUs.
Summary
In summary, dermal and inhalation exposures are expected lor this use N'A has not identified
additional uncertainties for this use beyond those included in Section 2 4 14. EPA identified primary
strengths and limitations and assigned an overall confidence to the occupational exposure scenario
inputs to the PBPK model, as discussed below I -PA considered the assessment approach, the quality of
the data, and uncertainties to determine the lc\ el of confidence Note that the effects of the limitations
on this assessment are discussed in Section 2 4 14
Primary Strengths
EPA assessed occupational inhalation exposure using directly applicable personal monitoring data,
which is the highest of the approach hierarchy, from one source with a data quality rating of medium.
EPA also used a modeled inhalation exposure concentration value, which is in the middle of the
approach hierarchy, from RIVM ( ) This data has a data quality rating of high. EPA determined
central tendency exposure duration from the inhalation monitoring data. EPA expects the central
tendency duration of inhalation and dermal exposure to be realistic, as the duration is task-based.
Primary I imitations
EPA assumed a high-end exposure duration of 8 hours based on the length of a full shift. The
representati\ eness of the assumed estimates of duration of inhalation and dermal exposure for the
assessed acti\ ities toward the true distribution of duration for all worker activities in this occupational
exposure scenario is uncertain. EPA did not find NMP concentration data and assumed workers may be
exposed to up to 10<)"() NMP since NMP is a carrier chemical, and carrier chemical concentrations may
be very high. Skin surface areas for actual dermal contact are uncertain. EPA did not find data on the use
of gloves for this occupational exposure scenario and assumed glove usage is likely based on
professional judgment, due to safety and quality standards in laboratories. The assumed glove protection
factor values are uncertain.
The monitoring data used for central tendency worker inhalation exposure is only one data point from a
1996 industrial hygiene report. The extent to which these data are representative of current worker
inhalation exposure potential is uncertain. The modeled high-end inhalation exposure concentration was
obtained from RIVM (2013) and not generated by EPA. The representativeness of the monitoring data
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and modeled exposure toward the true distribution of inhalation concentrations for this occupational
exposure scenario is uncertain.
Overall Confidence
Considering the overall strengths and limitations, the overall confidence of the PBPK input parameters
for this occupational exposure scenario is medium.
2.4.1.2.13 Cleaning
This scenario includes the use of cleaning products containing NMP I-'or this industrial and commercial
exposure scenario, EPA assessed inhalation, vapor-through-skin, and dermal exposures to cleaning
products containing NMP from the following activities:
• Dip cleaning / degreasing; and
• Spray / wipe cleaning.
While EPA does expect that workers may perform additional activities during this scenario, such as
unloading or sampling, EPA expects that cleaning activities present the largest range of potential
exposures.
Inhalation and Vayor-throush-Skin
EPA compiled inhalation monitoring data and modeled exposure concentration data for NMP-based
cleaning activities from published literature and used these data for the central tendency and high-end
(for full-shift) worker exposure concentrations presented in Table 2-50. EPA used the available
monitoring data for NMP use in cleaning that had the highest quality rating to assess exposure via this
use. The supplemental document Risk Evaluation for ,\-X/ei/iyl/>vrrolulone (NMP), Supplemental
Information on Occupational L.y/>o\iii\- . Issessment (U.S. EPA ) provides additional details.
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2523
Table 2-50. Summary of Parameters for PBPK Modeling of Worker Inhalation Exposure During
Work Activity
Parameter
Characterization
lull-Shift
NMP Air
Concent rat ion
Duration-
liased NMP
Air
Concentration
Source
Data
Quality
Rating
(ing/m\ 8-hr
TWA)
(nig/in')
TRIVM.
Central tendency (50th
percentile)
0.99
\o data
2013;
™10;
"rara
Medium
to high
Dip Cleaning /
Degreasing
High-end (95th
percentile)
2.75
\o data
1
a
Xiaofei et
al. 2000)
TRIVM.
Central tendency (50lh
percentile)
1 <>l
\o data
2013;
if- \
Spray / Wipe
Cleaning
2010;
Medium
to high
Nishimura
et al..
2009;
Bader et
al.. 2006)
1 ligh-end (^5lh
percentile)
3 3K
No data
2524
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Dermal
Table 2-51 summarizes the parameters used to assess dermal exposure during cleaning activities. Most
of these parameters were determined based on assumptions described in Section 2.4.1.1. EPA used data
from public comments, literature sources, and the Use and Market Profile for N-Methylpyrrolidone
(Atot 2017) to determine the NMP weight fraction. The underlying data have data quality ratings
ranging from medium to high. Because this scenario covers a variety of commercial and industrial sites,
EPA assumes that either no gloves are used or, if gloves are used, there is no permeation data to indicate
the glove material is protective for NMP, corresponding to a protection factor of 1. EPA assesses a
central tendency scenario assuming the use of gloves with minimal to no employee training,
corresponding to a protection factor of 5.
Table 2-51. Summary of Parameters for Worker Dermal Exposure to Liquids During Cleaning
Work
Activity
Parameter
Characterization
(•love
Protection
l'"aclor(s)
NMP
\Y'eight
l-'raction
Skin
Surface
Area
Kxposed "
Kxposurc
Duration
liody
W eight
il
I n it less
cm2
lir/dav
kg
Dip Cleaning
and
Degreasing
Central Tendency
5
0.S45
445 (f)
535 (m)
4
74 (f)
88 (m)
High-End
1
0
Sl)() (f)
1.D7D (m)
8
Spray/Wipe
Cleaning
Central Tendency
5
o 313
445 (f)
535 (m)
4
74 (f)
88 (m)
High-End
1
o l)89
890 (f)
1,070 (m)
8
a EPA assessed these exposure factors for both females and males. Values associated with females are denoted with (f) and
values associated with males arc denoted \\ itli < in i
PBPK Inputs
EPA assessed IMil'K paiameteis for cenli al tendency and high-end exposure scenarios based on the
characterizations listed in Table 2-52 The numeric parameters corresponding to the characterizations
presented in Table 2-52 are summarized in Table 2-53. These are the inputs used in the PBPK model.
Table 2-52. Characterization of Plil'K Vlodel Input Parameters for Cleaning
Scenario
Work
Air Concentration
Data
Characterization
Kxposurc
Skin
Surface
(•loves
NMP Weight
Kraction
Characterization
Activitv
Duration
Area
Kxposed
Central
Tendency
Dip
cleaning
Central tendency
(50th percentile)
Assumed
4 hours
1-hand
Yes
Central Tendency
High-end
Dip
cleaning
High-end (95th
percentile)
Assumed
8 hours
2-hand
No
High-end
Central
Tendency
Spray /
wipe
cleaning
Central tendency
(50th percentile)
Assumed
4 hours
1-hand
Yes
Central Tendency
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Scenario
Work
Activity
Air Concentration
Data
Characterization
Kxposure
Duration
Skin
Surface
Area
Kxposed
(•loves
NMP Weight
Kraction
Characterization
High-end
Spray /
wipe
cleaning
High-end (95th
percentile)
Assumed
8 hours
2-hand
No
High-end
Table 2-53. PBPK Model Input Parameters for Cleaning
Scenario
Work
Activity
Duralion-liascd
NMP Air
Concent rat ion
(nig/m')
Kxposurc
Duration
(hr)
Skin
Surface
Area
Kxposed
(cm2)il h
(•loves
Protection
Kactor
NMP
W eight
Iraction
liody
W eight
(kg)"
Central
Tendency
Dip
cleaning
1 OS
4
445 (f)
535 (m)
5
i) 845
74 (1)
88 (m)
High-end
Dip
cleaning
2.75
8
Son (f)
l.i)7i) (m)
1
0.999
74 (f)
88 (m)
Central
Tendency
Spray /
wipe
cleaning
2.02
4
445 (f)
535 (m)
5
0.313
74 (f)
88 (m)
High-end
Spray /
wipe
cleaning
3 38
S
Son (f)
1,070 (in)
i
0.989
74 (f)
88 (m)
a EPA assessed these exposure factors lor hoili females and males. Values associated with females are denoted with (f) and
values associated with males are denoted \\ nli (m)
bEPA assessed a skin surface area exposal lo liquid WIPofO.1 cnrforONUs for each scenario. However, EPA did not
assess glove usage (protection factor 1) for ()\l s
Summary
In summary, dermal and inhalation exposures are expected for this use. EPA has not identified
additional uncertainties for this use beyond those included in Section 2.4.1.4. EPA identified primary
strengths and limitations and assigned an overall confidence to the occupational exposure scenario
inputs to the IMiPK model, as discussed below. EPA considered the assessment approach, the quality of
the data, and uncertainties to determine the level of confidence. Note that the effects of the limitations
on this assessment are discussed in Section 2.4.1.4.
Primary Strengths
EPA assessed dermal exposure to central tendency and high-end NMP weight fractions, calculated as
the 50th and 95th percentiles, respectively, from a variety of data sources with data quality ratings
ranging from medium to high. To estimate inhalation exposure during dip cleaning, EPA used directly
applicable monitoring data, which is in the highest of the approach hierarchy, including data from 5
sources. These data have data quality ratings ranging from medium to high. To estimate inhalation
exposure during spray / wipe application, EPA used directly applicable monitoring data, which is in the
highest of the approach hierarchy, including data from 4 sources. These data have data quality ratings
ranging from medium to high.
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Primary Limitations
EPA did not find exposure duration data and assumed a high-end of 8 hours based on the length of a full
shift and a central tendency of 4 hours based on the mid-range of a shift. The representativeness of the
assumed estimates of duration of inhalation and dermal exposure for the assessed cleaning activities
toward the true distribution of duration for all worker activities in this occupational exposure scenario is
uncertain. Skin surface areas for actual dermal contact are uncertain. EPA did not find data on the use of
gloves for this occupational exposure scenario and assumed glove usage with minimal to no employee
training or no glove usage due to the wide-spread use of cleaning products. The assumed glove
protection factor values are uncertain.
The worker activities associated with the monitoring data used to assess inhalation exposure during dip
cleaning and spray/wipe cleaning were not detailed for all samples. Where EPA could not determine the
type of cleaning activities associated with a data point, EPA used the data in the estimates for both dip
and spray/wipe cleaning. For both occupational exposure scenarios, the represeiilali \ eness of the
monitoring data toward the true distribution of inhalation concentrations for this occupational exposure
scenario is uncertain.
Overall Confidence
Considering the overall strengths and limitations, the overall confidence of the PBPK input parameters
for this occupational exposure scenario is medium
2.4.1.2.14 Fertilizer Application
This scenario includes the use of fertilizers containing NMP. For this commercial exposure scenario,
EPA assessed inhalation. \ apoi-throuuh-skin, and dermal exposures to NiVlP during application of
fertilizers.
While EPA does expect that workers may perform additional activities during this scenario, such as
unloading or maintenance acti\ ities. I-PA expects that fertilizer application presents the largest range of
potential exposures
Inhalation and Vaiwr-tliroiinli-Skin
EPA did not find inhalation monitoring data for the application of fertilizers containing NMP. EPA
found modeled inhalation exposures during spray and fog application of agrochemicals (RIVM. 2013).
EPA uses the modeled exposures to assess potential inhalation exposures during this life cycle stage.
These data ha\ e a data quality rating of high.
The input parameters used lor the PBPK modeling based on the modeled exposures are summarized in
Table 2-54. EPA did not model data on short-term inhalation exposures during the application of
fertilizers containing. The supplemental document Risk Evaluation for N-Me thy Ipyrrolidone (2-
Pyrrolidinone, 1 Methyl-) (NMP), Supplemental Information on Occupational Exposure Assessment
( £019r) provides additional details.
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Table 2-54. Summary of Parameters for PBPK Modeling of Worker Inhalation Exposure During
Fertilizer Application
Work
Activity
Parameter
Characterization
l ull-Shift NMP
Air
Concentration
Duralion-liascd
NMP Air
Concentration
Source
Data
Quality
K;it in»
(mg/nr\ 8-hr
TWA)
(nig/nr')
Manual spray
or boom
application of
fertilizers
Central tendency
(unknown statistical
characterization)
2.97
No data
CRIVM.
2013)
High
High-end (unknown
statistical
characterization)
5.27
No data
Dermal
Table 2-55 summarizes the parameters used to assess dermal exposure during the use of agricultural
products containing NMP. Most of these parameters were determined based on assumptions described in
Section 2.4.1.1. EPA used data from literature, public comments, and l lie Use and Market Profile for N-
Methylpyrrolidone (Atot 2017) to determine the NMP weight fraction. The underlying data have a data
quality rating of high. Because this scenario co\ ers a variety of commercial and industrial sites, EPA
assumes that either no gloves are used or, if glo\ es are used, there is no permeation data to indicate the
glove material is protective for NMP, corresponding to a protection factor of 1. EPA assesses a central
tendency scenario assuming the use of gloves with minimal to no employee training, due to the
widespread nature of this occupational exposure scenario, corresponding to a protection factor of 5.
Table 2-55. Siimmarv of Parameters for \Yorker Dermal Kxposurc During
•ertilizer Ap
ilication
Work
Activity
Parameter
Characterization
(•love
Protection
l'"aclor(s)
NMP
W eight
l-'raction
Skin
Surface
Area
Kxposed "
Kxposurc
Duration
liody
W eight
il
I nitless
cm2
hr/day
Ivg
Manual spray
or boom
application of
fertilizers
Central Tendency
5
0.001
445 (f)
535 (m)
4
74 (f)
88 (m)
High-I jul
1
0.07
890 (f)
1,070 (m)
8
a EPA assessed these exposure Incinrs I'm- both females and males. Values associated with females are denoted with (f) and
values associated with mules are denoted with (m).
PBPK Inputs
EPA assessed PBPK parameters for central tendency and high-end exposure scenarios based on the
characterizations listed in Table 2-56.
The numeric parameters corresponding to the characterizations presented in Table 2-56 are summarized
in Table 2-57. These are the inputs used in the PBPK model.
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Table 2-56. Characterization of PBPK Model Input Parameters for Fertilizer Application
Scenario
Work
Activity
Air
Concentration
Data
Characterization
Kxposure
Duration
Skin
Surface
Area
Kxposed
(•loves
NMP Weight
Kraction
Characterization
Central
Tendency
Manual
spray or
boom
application
Central tendency
(unknown
statistical
characterization)
Calculated
4-hr TWA
from the 8-
hr TWA
data
1-hand
Yes
Central Tendency
High-end
Manual
spray or
boom
application
High-end
(unknown
statistical
characterization)
Based on
8-hr TWA
data
2-hand
No
High-end
Table 2-57. PBPK Model Input Parameters for Kertilizer Application
Scenario
Duralion-liascd
NMP Air
Concent rat ion
(nig/nr*)
Kxposurc
Duration
(In)
Skin Surface
Area
Kxposed
(cm2)1,b
(•loves
Protection
Kactor
NMP
Weight
Kraction
liodv
Weight
(kg)"
Central
Tendency
5 94
4
445 (0
535 (m)
5
0.001
74 (f)
88 (m)
High-end
5.27
8
890 (f)
1,070 (m)
1
0.07
74 (f)
88 (m)
a EPA assessed these exposure faciois lor hoi li females and males. Values associated with females are denoted with (f) and
values associated with males are denoted \\ uli (ml
bEPA assessed a skin surface area e\posed lo liquid W1P of u 1 cur for ONUs for each scenario. However, EPA did not
assess glove usage (protection factor 1) lor ONUs.
Summary
In summary, dermal and inhalation exposures are expected for this use. EPA has not identified
additional uncertainties for this use beyond those included in Section 2.4.1.4. EPA identified primary
strengths and limilalions and assigned an overall confidence to the occupational exposure scenario
inputs to the PBPK model, as discussed below. EPA considered the assessment approach, the quality of
the data, and uncertainties lo determine the level of confidence. Note that the effects of the limitations
on this assessment arc discussed in Section 2.4.1.4.
Primary Strengths
EPA assessed dermal exposure to 0.1 to 7% NMP, based on data from public comments and literature,
which have data quality ratings of high. EPA assessed occupational inhalation exposure during fertilizer
application using a modeled inhalation exposure concentration value, which is in the middle of the
approach hierarchy, from RIVM (2013). This data has a data quality rating of high.
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Primary Limitations
EPA did not find exposure duration data and assumed a high-end of 8 hours based on the length of a full
shift and a central tendency of 4 hours based on the mid-range of a shift. The representativeness of the
assumed estimates of duration of inhalation and dermal exposure toward the true distribution of duration
for all worker activities in this occupational exposure scenario is uncertain. Skin surface areas for actual
dermal contact are uncertain. EPA did not find data on the use of gloves for this occupational exposure
scenario and assumed glove usage with minimal to no employee training or no glove usage due to the
commercial nature of this use. The assumed glove protection factor values are uncertain. The modeled
inhalation exposure concentration was obtained from RIVM (201: ) and not generated by EPA. The
representativeness of the modeled exposure toward the true distribution of inhalation concentrations for
this occupational exposure scenario is uncertain.
Overall Confidence
Considering the overall strengths and limitations, the o\ era! I confidence of the PliPk input parameters
for this occupational exposure scenario is medium.
2.4.1.2.15 Wood Preservatives
This scenario includes the use of wood preservatives containing WIP I-'or this commercial exposure
scenario, EPA assessed inhalation, vapor-through-skin, and dermal exposures to NMP during brush
application of these wood preservatives. EPA does not expect other application methods because the
identified wood preservative production containing NMP is a paste.
Based on the process description, EPA expects that workers apply the paste wood preservative directly
from its container using a scraper N\\ does not expect unloading activities or the use of equipment
requiring maintenance or cleaning I-PA expects the actual application of wood preservatives presents
the largest range of potential exposures.
Inhalation and Vapor-thromili-Shin
EPA compiled air concentration monitoring data and modeled data for NMP-based wood preservative
application from published literature sources. Due to limited relevance and quality of monitoring data
and modeling estimates lor sol\ ents used in the application of wood preservatives found in the published
literature. I-IW used modeling estimates with the highest data quality for this use.
The modeled exposure from ln ush application is summarized into the input parameters used for the
PBPK modeling in Table 2-5S I-PA did not find data on short-term exposures for this life cycle stage.
The supplemental document Risk /.valuationfor N-Methylpyrrolidone (2-Pyrrolidinone, 1 Methyl-)
(NMP), Supplemental Information on Occupational Exposure Assessment ( r) provides
additional details.
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Table 2-58. Summary of Parameters for Wood Preservatives
Work
Activity
Parameter
( haraclerizalion
lull-Shift NMP
Air
Concentration
Duration-liascd
NMP Air
Concenl rat ion
Source
Data
Quality
Rating
(mg/nr\ 8-hr
TWA)
(nig/nr')
Brush
Application
Single Estimate
4.13
jNo data
(
2013)
High
Dermal
Table 2-59 summarizes the parameters used to assess dermal exposure during the use of wood
preservatives containing NMP. Most of these parameters were determined based on assumptions
described in Section 2.4.1.1. EPA used data from the Use and Market Profile Jor S-\ lethylpyrrolidone
(Atot 2017) to determine the NMP weight fraction. Because this scenario cov ers a \ ariety of commercial
and industrial sites, EPA assumes that either no glo\es are used or, if gloves are used, there is no
permeation data to indicate the glove material is prolecli\ e lor \\ll\ corresponding to a protection
factor of 1. EPA assesses a central tendency scenario assuming the use of gloves with minimal to no
employee training, corresponding to a protection factor of 5
Table 2-59. Summary of Parameters for W orker Dermal Kxposure to Wood Preservatives
Work
Parameter
(Jove
Protection
l'actor(s)
NMP
Weight
Skin
Surface
Area
Kx posed 11
Kxposurc
Duration
liody
W eight
Activity
Characterization
l-'raction
il
I n it less
cm2
lir/dav
Brush
Central Tendency
5
0.01
445 (f)
535 (m)
4
74(f)
Application
High-End
1
0.01
890 (f)
1,070 (m)
8
88 (m)
a EPA assessed these exposure factors for hoili females and males. Values associated with females are denoted with (f) and
values associated with males are denoted \x ilh (im
PBPK Inputs
EPA assessed IMiPK parameters for central tendency and high-end exposure scenarios based on the
characterizations listed in TaMe 2-(<). The numeric parameters corresponding to the characterizations
presented in TaMe 2-O0 are summarized in Table 2-61. These are the inputs used in the PBPK model.
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Table 2-60. Characterization of PBPK Mode
Input Parameters for Wood Preservatives
Scenario
Work
Activity
Air
Concentration
Data
Characterization
Kxposure
Duration
Skin
Surface
Area
Fxposed
(•loves
NMP Weight
Fraction
Characterization
Central
Tendency
Brush
application
Single Estimate
Assumed
4 hours
1-hand
Yes
Single data point
available and used
for both exposure
scenarios
High-end
Brush
application
Single Estimate
Assumed
8 hours
2-hand
No
Single data point
available and used
for both exposure
scenarios
Table 2-61. PBPK Model Input Parameters for Wood Preservatives
Scenario
Duralion-liascd
NMP Air
Concent rat ion
(nig/nr*)
Kxposurc
Duration
(In)
Skin Surface
Area
Kxposed
(cm2)
(•loves
Protection
Factor
NMP
Weight
Fraction
liodv
Weight
(kg)"
Central
Tendency
8.26
4
445 (f)
535 (m)
5
0.01
74 (f)
88 (m)
High-end
4 13
8
Sl)() (f)
I.D7D (ill)
i
0.01
74 (f)
88 (m)
" EPA assessed these exposure laclors I'm- boili females and males. Values associated with females are denoted with (f) and
values associated with males arc denoted \\ nli < in).
bEPA assessed a skin surface area exposal ol'n 1 cm2for ONUs for each scenario. However, EPA did not assess glove
usage (protectionfactor = 1) lor ()\l '
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Primary Limitations
EPA did not find exposure duration data and assumed a high-end of 8 hours based on the length of a full
shift and a central tendency of 4 hours based on the mid-range of a shift. The representativeness of the
assumed estimates of duration of inhalation and dermal exposure toward the true distribution of duration
for all worker activities in this occupational exposure scenario is uncertain. Skin surface areas for actual
dermal contact are uncertain. EPA did not find data on the use of gloves for this occupational exposure
scenario and assumed glove usage with minimal to no employee training or no glove usage due to the
commercial nature of this use. The assumed glove protection factor values are uncertain. The modeled
inhalation exposure concentration was obtained from RIVM (2013) and not generated by EPA. The
representativeness of the modeled exposure toward the true distribution of inhalation concentrations for
this occupational exposure scenario is uncertain.
Overall Confidence
Considering the overall strengths and limitations, the o\ era! I confidence of the PliPk input parameters
for this occupational exposure scenario is medium.
2.4.1.2.16 Recycling and Disposal
For this industrial and commercial exposure scenario, EPA assessed inhalation, vapor-through-skin, and
dermal exposures from the unloading of various containers (i.e . drums, tank trucks, rail cars) containing
waste NMP. While EPA does expect that workers may perform additional activities during this scenario,
such as sampling or maintenance work, EPA expects that unloading acli\ ities present the largest range
of potential exposures.
Inhalation and Vayor-throusli-Sliin
EPA did not find monitoring data on the handling of NMP wastes at disposal and recycling sites. EPA
therefore compiled the same monitoring and modeled exposure concentration data for this life cycle
stage as that for manufacturing As described for Manufacturing in Section 2.4.1.2.1, due to limited
relevance and quality of monitoring data and modeling estimates found in the published literature, EPA
used modeling estimates with the highest data quality for this use, as further described below. The Tank
Truck and Rail car Loading and Unloading Release and Inhalation Exposure Model involves
deterministic modeling and the Drum I oadingand Unloading Release and Inhalation Exposure Model
invol\ es probabilistic modeling.
The inhalation exposure concentrations modeled by EPA for unloading of NMP are summarized into the
input parameters used for the PBPK modeling in Table 2-62. The modeled exposure concentrations are
the same as those for Manufacturing and Repackaging; however, the exposure durations are different
because they are based on the NMP volume unloaded for the exposure scenario. Note that the exposure
duration for the central tendency and high-end exposure scenarios are the same for unloading drums
because the unloading rate does not vary in that model. The supplemental document Risk Evaluation for
N-Methylpyrrolidone (2-Pyrrolidinone, 1 Methyl-) (NMP), Supplemental Information on Occupational
Exposure Assessment (U.S. EPA. 2019r) provides additional details.
Page 127 of 487
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Table 2-62. Summary of Parameters for PBPK Modeling of Worker Inhalation Exposure During
Recycling and Disposal
Work
Activity
Parameter
Characterization
l ull-Shift NMP Air
Concentration
Duration-
liased NMP
Air
Concent rat ion
Source
Data
Quality
Rating
(mg/ni'. 8-hr TWA)
(nig/nr*)
Unloading
bulk
containers
Central tendency
(50th percentile)
0.048
0.760 (duration
= 0.5 hr)
lank Truck
and Railcar
I <>aihng and
I nloading
Release and
Inlialalion
Ii\-/>osiire
Model f«j.
Not
applicable21
High-end (95th
percentile)
0.190
1.52 (duration
= 1 hr)
Unloading
drums
Central tendency
(50th percentile)
0 124
1 (->5 (duration
i) M)3 hr)
Drum
Loading and
Unloading
Release and
Inhalation
Exposure
Model (U.S.
EPA. 2.013a)
Not
applicablea
High-end (95th
percentile)
0 441
5 S5 (duration
i) M)3 hr)
11 EPA models are standard sources used h\ IP \ lor occupational e\posure assessments. EPA did not systematically review
models that were developed In IP \
Dermal
Table 2-63 summarizes the parameters used lo assess dermal exposure during worker handling of wastes
containing NMP. Most parameters were determined based on assumptions described in Section 2.4.1.1.
The data submitted In SI A for the use of NMP in the production of semiconductors (discussed in
Section 2 4 I 2.8) include one inhalation monitoring data point for the loading of trucks with waste
NMP. This data point indicates that NMP is 92% in the handled waste material (! 19). EPA uses
this concentration for the central tendency NMP weight fraction. Due to lack of additional information
on the concentration of NMP in waste solvents, for the high-end value, EPA assumes that waste NMP
may contain very little impurities and be up to 100 weight percent NMP (e.g., residues of pure NMP in
shipping containers that have been unloaded and sent without cleaning for reclamation or disposal). For
this scenario, EPA assesses both high-end and central tendency scenarios assuming the use of gloves
with basic employee training, corresponding to a protection factor of 10.
Page 128 of 487
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Table 2-63. Summary of Parameters for Worker Dermal Exposure During Recycling and Disposal
Work
Activity
Parameter
Characterization
(Jove
Protection
Kactor(s)
YMP
Weight
Kraction
Skin
Surface
Area
Kx posed 11
Kxposure
Duration
liody
Weight
il
I n it less
cm2
lir/dav
Ivli
Unloading
bulk
containers;
Unloading
drums
Central Tendency
10
0.92
445 (f)
535 (m)
4
74(f)
88 (m)
High-end
10
1
890 (f)
1,07') (in)
8
a EPA assessed these exposure factors for both females and males. Values associated wiili females arc denoted with (f) and
values associated with males are denoted with (m).
PBPK Inputs
EPA assessed PBPK parameters for central tendency and high-end exposure scenarios based on the
characterizations listed in Table 2-64. The numeric parameters corresponding to the characterizations
presented in Table 2-64 are summarized in
Table 2-65. These are the inputs used in the PBPK model.
Table 2-64. Characterization of PBPK Mode Input Parameters for Recycle and Disposal
Scenario
Work
Activity
Air
Concentration
Data
Characterization
Kxposurc
Duration
Skin
Surface
Area
Exposed
Gloves
YM P W eight
Fraction
Characterization
Central
Tendency
I nloading
bulk
containers
Central tendency
(50lh percentile)
Duration
calculated
bv model
1-hand
\ es
Central tendency
High-end
Unloading
drums
1 liuh-end (l>5lh
percentile)
Duration
calculated
by model
2-hand
Yes
High-end
Table 2-65. PBPK "Model Inpul Parameters for Recycle and
disposal
Scenario
Duralion-liascd
NMP Aii-
Concent rat ion
(nig/nr')
Kxposurc
Duration
(In)
Skin Surface
Area
Kxposed
(cm2) "¦h
(•loves
Protection
Kactor
NMP
W eight
Kradion
liody
W eight
(kg)"
Central
Tendency
0.760
0.5
445 (f)
535 (m)
10
0.92
74 (1)
88 (m)
High-end
5.85
0.603
890 (f)
1,070 (m)
10
1
74 (f)
88 (m)
a EPA assessed these exposure factors for both females and males. Values associated with females are denoted with (f) and
values associated with males are denoted with (m).
bEPA assessed a skin surface area exposed to liquid NMP of 0.1 cm2for ONUs for each scenario. However, EPA did not
assess glove usage (protection factor = 1) for ONUs.
Page 129 of 487
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Summary
In summary, dermal and inhalation exposures are expected for this use. EPA has not identified
additional uncertainties for this use beyond those included in Section 2.4.1.4. EPA identified primary
strengths and limitations and assigned an overall confidence to the occupational exposure scenario
inputs to the PBPK model, as discussed below. EPA considered the assessment approach, the quality of
the data, and uncertainties to determine the level of confidence. Note that the effects of the limitations
on this assessment are discussed in Section 2.4.1.4.
Primary Strengths
Modeling, in the middle of the approach hierarchy, was used to estimate occupational inhalation
exposure concentrations for both the unloading of NMP from bulk containers and from drums. For
modeling of these air concentrations, EPA attempted to address variability in input parameters by
estimating both central tendency and high-end parameter values. Additionally, lor modeling of air
concentrations during the unloading of drums, EPA used Monte Carlo simulation lo capture variability
in input parameters. EPA expects the duration of inhalation and dermal exposure to be realistic for the
unloading activities, as the durations are based on the length of time to unload NMP from specific
container sizes (i.e., tank trucks, rail cars, and drums).
Primary Limitations
The representativeness of the estimates of duration of inhalation and dermal exposure for the unloading
activities toward the true distribution of duration lor all w orker activities in this occupational exposure
scenario is uncertain. EPA did not find NMP concentration data and assumed waste NMP may contain
very little impurities and be up to 100% NMP. Skin surface areas for actual dermal contact are
uncertain. EPA did not find data on the use of gloves lor this occupational exposure scenario and
assumed glove usage w ith basic employee training is likely based on professional judgment. The
assumed glove protection factor values are uncertain. For the modeling of NMP air concentrations, EPA
is uncertain of the accuracy of the emission factors used to estimate fugitive NMP emissions and thereby
estimate worker inhalation exposure concentration. The representativeness of the modeling results
toward the true distribution of inhalation concentrations for this occupational exposure scenario is
uncertain.
Overall (\mfidence
Considering the overall strengths and limitations, the overall confidence of the PBPK input parameters
for this occupational exposure scenario is medium.
2.4.1.3 Summary of Occupational Exposure Assessment
Table 2-66 shows the occupational dermal and inhalation exposure parameters used in the PBPK
modeling for this assessment. The skin surface area and body weight dermal parameters were specific to
PESS of interest: males, pregnant women, and women of childbearing age who may become pregnant.
For each Occupational Exposure Scenario, a central scenario and a higher-end scenario are provided.
Table 2-67 shows the results of the PBPK modeling.
For high-end scenarios where glove use was assumed and MOEs were above the benchmark MOE, EPA
conducted additional modeling of exposures for no glove use to determine whether lack of glove use
could result in MOEs below the benchmark MOE. The results of this additional modeling are shown in
Section 4.2.2.
Page 130 of 487
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Table 2-66. Parameter Inputs to PBPK for Central and High-End Scenarios by Use
I so Scenario
Scenario
Characleri/alion
Suh-sccnario
Weigh l
Fraction in
rormulalion
sui-r
Area
exposed
(o liquid
(enr) •'
Exposure
du ration
(hi)
Duralion-
hascd Air
C one
(mg/m()
(Jo\es
Proieclion
Faclor
Section 2.4.1.2.1
Manufacturing
Central tendency
Bulk container
loading
1
445 (f)
535 (m)
0.5
0.76
10
High-end
Drum loading
1
890 (f)
1,070
(m)
2.06
5.85
10
Section 2.4.1.2.2
Repackaging
Central tendency
Bulk container
unloading
1
445 (0
535 (m)
ii 5
0.76
10
High-end
Drum unloading
1
890 (f)
1,070
(m)
2 lib
5 85
10
Section 2.4.1.2.3
Chemical
Processing,
Excluding
Formulation
Central tendency
Drum unloading
1
445 (f)
535 (m)
0.36
1 (>5
10
High-end
Drum unloading
1
X'Jd (0
I.U70
nil)
0.36
5.85
10
Section 2.4.1.2.4
Incorporation
into
Formulation,
Mixture, or
Reaction
Product
Central tendency
Drum unloading
1
445 i E)
535 im)
0.36
1.65
10
High-end
Maintenance,
bottling, shipping,
loading
1
890 u;
1.070
(m)
8
12.8
10
Section 2.4.1.2.5
Melal Finishing
Cenlial k-ndaic>
Spia> application
0.6
445 (f)
535 (m)
4
0.53
5
Hiyh-cnd
Spia> application
0.9
890 (f)
1,070
(m)
8
4.51
1
( enlial laidaic>
Dip application
0.6
445 (f)
535 (m)
4
1.98
5
High-end
Dip application
0.9
890 (f)
1,070
(m)
8
2.75
1
( enlial tendency
Brush application
0.6
445 (f)
535 (m)
4
8.26
5
11 lyh-oiid
Brush application
0.9
890 (f)
1,070
(m)
8
4.13
1
Section 2.4.1.2.6
Removal of
Paints,
Coatings,
Adhesives and
Sealants
Central tendency
Miscellaneous
removal
0.305
445 (f)
535 (m)
1
13.2
5
High-end
Miscellaneous
removal
0.695
890 (f)
1,070
(m)
8
64
1
Central tendency
Graffiti removal
0.5
445 (f)
535 (m)
4
2.02
5
High-end
Graffiti removal
0.613
890 (f)
8
4.52
1
Page 131 of 487
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I so Scenario
Scenario
Characteri/ation
Siih-sccnario
Weight
l-'raction in
formulation
Surf
Area
exposed
lo 1 i(|ii id
(enr) '
Exposure
duration
(In)
Duralion-
hascd Air
C one
(nig/in4)
(Jo\es
Protection
I'actor
1,070
(m)
Section 2.4.1.2.7
Application of
Paints,
Coatings,
Adhesives and
Sealants
Central tendency
Spray application
0.02
445 (f)
535 (m)
4
0.53
5
High-end
Spray application
0.534
890 (f)
1.070
(m)
8
4.51
1
Central tendency
Roll/curtain
application
0.02
445 (f)
535 (m)
4
0.06
5
High-end
Roll/curtain
application
ii 534
890 (f)
1,070
(m)
8
ii |l;
1
Central tendency
Dip application
(i (12
445 (0
535 (m)
4
1 lJ8
5
High-end
Dip application
0.534
8<;n (f)
I.U70
nil i
8
2.75
1
Central tendency
Brush application
(i 02
445 (l"i
535 (in i
4
8.26
5
High-end
Brush application
ii 534
890(l"i
1.070
(m)
8
4.13
1
Section 2.4.I.2.S
Electronic Paris
Manufacturing
Central tendency
( onlainor handling,
small containers
0.60
445 (0
535 (m)
6
1.01
10
High-end
( onlainor handling,
small containers
0.75
890 (f)
1,070
(m)
12
0.608
10
( enlial tendency
Container handling,
drums
0.5
445 (f)
535 (m)
6
0.026
10
1 liyli-end
( onlainor handling,
drums
0.75
890 (f)
1,070
(m)
12
1.54
10
(Central tendency
Fab worker
0.15
445 (f)
535 (m)
6
0.276
10
1 liyh-cnd
Fab worker
0.999
890 (f)
1,070
(m)
12
0.405
10
Central tendency
Maintenance
0.55
445 (f)
535 (m)
6
0.040
10
High-end
Maintenance
1
890 (f)
1,070
(m)
12
0.690
10
Central tendency
Virgin NMP truck
unloading
1
445 (f)
535 (m)
4
9.56
10
High-end
Virgin NMP truck
unloading
1
890 (f)
1,070
(m)
8
4.78
10
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I so Scenario
Scenario
Characleri/alion
Suh-scenai'io
Weigh I
l-'raclion in
roi'inulalion
Surf
Area
exposed
lo 1 i(|ii id
(enr) '
Kxposiirc
du ration
(In)
Duralion-
hascd Air
C one
(mg/m()
(Jo\es
Protection
I'aclor
Central tendency
Waste truck loading
0.92
445 (f)
535 (m)
4
1.42
10
High-end
Waste truck loading
0.95
890 (f)
1,070
mi i
8
0.709
10
Section 2.4.1.2.9
Printing and
Writing
Central tendency
Printing
0.05
445 i l"i
535 i in i
4
0.016
5
High-end
Printing
0.07
890 (f)
1,070
(m)
8
i U72
1
Central tendency
Writing
u 1
1
0.5
0
5
High-end
Writing
ii :
1
0.5
0
1
Section
2.4.1.2.10
Soldering
Central tendency
Soldering
0 ill
445 (0
535 (m)
4
0
5
High-end
Soldering
0.025
8
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PEER REVIEW DRAFT, DO NOT CITE OR QUOTE
I so Scenario
Scenario
Characteri/ation
Suh-scenai'io
Weight
Fraction in
formulation
Surf
Area
exposed
lo 1 i(|ii id
(cnr) '
Kxposure
du ration
(In)
Duration-
hascd Air
C one
(ing/m4)
(Jo\es
Protection
Factor
Section
2.4.1.2.16
Recycling and
Disposal
Central tendency
Bulk container
unloading
0.92
445 (f)
535 (m)
0.5
0.760
10
High-end
Drum unloading
1
890 (f)
1,070
(m)
I) 603
5.85
10
Note: The prevalence of respirator use is not known but may be unlikely for most scenarios. Some "what-if' scenarios were
generated assuming the use of APF 10 respirators. These scenarios are shown in Section 4.2 2
a EPA assessed these exposure factors for both females and males. Values associated Willi females ;ire denoted with (f) and
values associated with males are denoted with (m).
2851
2852
2853 Table 2-67. PBPK Exposure Results for Central and Nigh-End Worker and OM Scenarios by
2854 Use
Acute
Kxposiirc.
Peak hlood
Chronic
Exposure.
concentration
Al C (lir
Scenario
(mg/l.)
mg/L)
Chronic Kxposiirc. Al ( (lir
I se Scenario
Characteri/ation
Suh-scenario
(female)
(male)
mg/L) (OM )
Section 2.4.1.2.1
Central tendency
Bulk container
loading
n 42
(I X(i
0.011
Manufacturing
High-end
Drum loading
2.14
7.4
0.31
Section 2.4.1.2.2
Repackaging
Central tendency
Bulk container
unloading
0.42
0.86
0.011
High-end
Di li in unloading
2.14
7.4
0.31
Section 2.4.1.2.3
Chemical
Processing,
Central tendency
Drum unloading
0.35
0.63
0.016
Excluding
Formulation
1 ligli-aid
Drum unloading
0.72
1.3
0.055
Section 2.4.1.2.4
Incorporation
into
(Central tendency
Drum unloading
0.35
0.63
0.016
Formulation.
Mixture, or
Reaction
Product
1 ligh-cnd
Maintenance,
bottling, shipping,
loading
4.39
30.9
2.63
Cuitral tendency
Spray application
1.83
8.3
0.053
High-end
Spray application
46.3
347
0.94
Section 2.4.1.2.5
Central tendency
Dip application
1.87
8.5
0.20
Metal Finishing
High-end
Dip application
46.2
346
0.58
Central tendency
Brush application
2.01
9.1
0.81
High-end
Brush application
46.3
347
0.86
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1 so Scenario
Scenario
Charac(cri/a(ion
Suh-sccnario
Acule
Kxposure.
Peak blood
concentration
(mg/l.)
(female)
Chronic
Exposure.
Al ( (In
mg/l.)
(male)
Chronic llxposure. Al ( (lir
mg/l.) |()\l )
Section 2.4.1.2.6
Removal of
Paints,
Coatings,
Adhesives and
Sealants
Central tendency
Miscellaneous
removal
0.51
1.4
0.32
High-end
Miscellaneous
removal
36.5
268
13
Central tendency
Graffiti removal
1.56
7.1
0.20
High-end
Graffiti removal
29.2
212
0.93
Section 2.4.1.2.7
Application of
Paints,
Coatings,
Adhesives and
Sealants
Central tendency
Spray application
0.07
0.32
0.052
High-end
Spray application
24.9
179.0
0.93
Central tendency
Roll/curtain
application
D.II6
0.28
0.0059
High-end
Roll/curtain
application
24 7
178.4
ii u52
Central tendency
Dip application
i) III
u.47
0.19
High-end
Dip application
24 X
179.1
0.57
Central tendency
Brush application
0.25
1.08
0.81
High-end
Brush application
24.8
1 70 5
0.85
Section 2.4.1.2.8
Electronic Parts
Manufacturing
Central tendency
Container handling,
small containers
1 1
(. 3 1
0.15
High-end
Container handling,
small containers
31 8
0.21
Central tendency
Container handling,
drums
0.86
5.13
0.0043
High-end
( onlaincr handling,
drums
3.4
32.1
0.50
Central tendency
Fab worker
0.26
1.57
0.041
High-end
Fah worker
4.5
42.8
0.16
Central lendenev
Maintenance
0.95
5.65
0.0064
1 1 l!J ll-Olltl
Maintenance
4.5
42.9
0.25
Central tendency
Virgin NMP truck
unloading
1.7
7.83
0.94
1 ligh-end
Virgin NMP truck
unloading
4.1
29.2
0.99
( entral tendency
Waste truck loading
1.4
6.45
0.14
lli^h-cnd
Waste truck loading
3.7
26.0
0.17
Section 2.4.1.2.9
Printing and
Writing
( enlral tendency
Printing
0.15
0.68
0.0017
Hidi-end
Printing
2.8
19.5
0.037
Central tendency
Writing
0.00019
0.00032
0.000032
High-end
Writing
0.0019
0.0032
0.00032
Section
2.4.1.2.10
Soldering
Central tendency
Soldering
0.03
0.14
0.000025
High-end
Soldering
0.97
6.8
0.00063
Section
2.4.1.2.11
Commercial
Central tendency
Aerosol Degreasing
0.21
0.6
0.49
High-end
Aerosol Degreasing
15.9
113
8.91
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1 so Scenario
Scenario
C haracteri/ation
Suh-scenai'io
Acule
Kxposure.
Peak blood
concentration
(nig/I.)
(1'cmalc)
Chronic
llxposiire.
Al ( (In
mg/L)
(male)
Chronic Kxposure. Al ( (lir
mii/l ) lO\l )
Automotive
Servicing
Section
2.4.1.2.12
Laboratory Use
Central tendency
Laboratory use
1.0
3.4
0.010
High-end
Laboratory use
4.1
2<;
0.81
Section
2.4.1.2.13
Cleaning
Central tendency
Dip Cleaning
2.62
12
0.20
High-end
Dip Cleaning
52.6
0.58
Central tendency
Spray / Wipe
Cleaning
0.99
4.5
0.20
High-end
Spray / Wipe
Cleaning
52 ii
393
ii 71
Section
2.4.1.2.14
Fertilizer
Application
Central tendency
Manual spray or
boom application
(1.14
n.60
(I 58
High-end
Manual spray or
boom application
2.9
20.6
1.1
Section
2.4.1.2.15
Wood
Preservatives
Central tendency
Brush application
0.22
o<;5
0.81
High-end
Brush application
ii 51
3.5
0.84
Section
2.4.1.2.16
Recycling and
Disposal
Central tendency
Bulk container
unloading
(I ."X
(I 7K)
0.011
1 ligh-end
Drum unloading
0.96
2.14
0.091
2.4.1.4 Summary of I ncerlainties for Occupational Exposure Parameters
Key uncertainties in the occupational exposure parameters are summarized below. Most parameters are
related specifically to the route of dermal contact with liquids by workers, while air concentrations are
related to the routes of inhalation and \ apor-through-skin exposure. The body weight parameter is
related to all of these routes The assumed values for human body weight have relatively lower
uncertainties, and the median \ allies used may underestimate exposures at the high-end of PBPK
exposure results
Dermal Exposure Parameters
The dermal exposure parameters used in this assessment have uncertainties because many parameters
lack data and were therefore based on assumptions. The assumed parameter values with the greatest
uncertainties are glove use and effectiveness (using protection factors based on the ECETOC TRA
model that are what-if type values as described in Section 2.4.1.1), durations of contact with liquid, and
skin surface areas for contact with liquids. The assumed values for effectiveness, durations of contact,
and surface areas for contact may or may not be representative of actual values. The assumed values for
NMP concentrations in formulations have relatively lower uncertainties. The midpoints of some ranges
serve as substitutes for 50th percentiles of the actual distributions and high ends of ranges serve as
substitutes for 95th percentiles of the actual distributions. However, these substitutes are uncertain and
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are weak substitutes for the ideal percentile values. Generally, EPA cannot determine whether most of
these assumptions may overestimate or underestimate exposures. However, high-end duration of dermal
contact estimates of 8 hours may be more likely to overestimate exposure potential to some extent, and
some activity-based durations may be more likely to underestimate exposure potential to some extent.
For many OESs, the high-end surface area assumption of contact over the full area of two hands likely
overestimates exposures. Occupational non-users (ONUs) may have direct contact with NMP-based
liquid products due to incidental exposure at shared work areas with workers who directly work with
NMP, and the estimate of zero surface area contact may underestimate their exposure. The parameter
values NMP concentrations are from available data and are likely to have a relatively low impact on the
magnitude (less than an order of magnitude, or factor of 10) of overesti mation or underestimation of
exposure. The impact of vapors being trapped next to the skin during glo\ e use is also uncertain.
Inhalation and Vayor-throush-Skin Exposure Parameters
Where monitoring data are available, limitations of the data also introduce uncerlai lilies into the
exposures. The principal limitation of the air concentration data is the uncertainty in the
representativeness of the data. EPA identified a limited number of exposure studies and data sets that
provided data for facilities or job sites where NMP was used Some of these studies primarily focused on
single sites. This small sample pool introduces uncertainty as it is unclear how representative the data
for a specific end use are for all sites and all workers across the I S Differences in work practices and
engineering controls across sites can introduce \ ariability and limit the representativeness of any one site
relative to all sites. Age of the monitoring data can also introduce uncertainty due to differences in work
practices and equipment used at the time the monitoring data were taken and those used currently, so the
use of older data may over- or underestimate exposures. Additionally, some data sources may be
inherently biased. For example, bias may be present if exposure monitoring was conducted to address
concerns regarding adverse human health effects reported following exposures during use. The effects of
these uncertainties on the occupational exposure assessment are unknown, as the uncertainties may
result in either over or underestimation of exposures depending on the actual distribution of inhalation
exposure concentrations and the \ ariability of work practices among different sites.
The impact of these uncertainties precluded l-IW from describing actual parameter distributions. In most
scenarios where data were available. IPX did not find enough data to determine complete statistical
distributions. Ideally. I-PA would like to know 50th and 95th percentiles for each exposed population. In
the absence of percentile data for monitoring, the means or midpoint of the range serve as substitutes for
50th percentiles of the actual distributions and high ends of ranges serve as substitutes for 95th
percentiles of the actual distributions. However, these substitutes are uncertain and are weak substitutes
for the ideal percentile values. The effects of these substitutes on the occupational exposure assessment
are unknown, as the substitutes may result in either over or underestimation of exposures depending on
the actual distribution
Where data were not available, the modeling approaches used to estimate air concentrations also have
uncertainties. Parameter values used in models did not all have distributions known to represent the
modeled scenario. It is also uncertain whether the model equations generate results that represent actual
workplace air concentrations. Some activity-based modeling does not account for exposures from other
activities, which may result in underestimates of exposures. When EPA does not have ONU-specific
exposure data, EPA's assumption that 50th percentile air concentrations predicted for workers in these
activities are a good approximation of exposure is uncertain. It is not known whether this assumption
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underestimates or overestimates exposure for ONUs. Additional model-specific uncertainties are
included below. In general, unless specified otherwise, the effects of the below model-specific
uncertainties on the exposure estimates are unknown, as the uncertainties may result in either over or
underestimation on exposures depending on the actual distributions of each of the model input
parameters.
Tank Truck and Railcar Loading and Unloading Release and Inhalation Exposure Model
For manufacturing; repackaging; and recycling and disposal, the Tank Truck and Railcar Loading and
Unloading Release and Inhalation Exposure Model was used to estimate the airborne concentration
associated with generic chemical loading scenarios at industrial facilities. Specific uncertainties
associated with this model are described below:
• After each loading event, the model assumes saturated air containing Wll' that remains in the
transfer hose and/or loading arm is released to air The model calculates the quantity of saturated
air using design dimensions of loading systems pnhlished in the OPW Engineered Systems
catalog and engineering professional judgment. These dimensions may not be representative of
the whole range of loading equipment used at industrial facilities handling NMP.
• The model estimates fugitive emissions from equipment leaks using total organic compound
emission factors from EPA's Protocol for Equipment Leak I .mission Estimates (U.S. EPA.
1995). and professional judgment on the likely equipment type used for transfer (e.g. number of
valves, seals, lines, and connections). The applicability of these emission factors to NMP, and
the accuracy of EPA's assumption on equipment type are not known.
Drum Loading and Unloading Release and Inhalation Exposure \ lodel
For chemical processing, excluding formulation and incorporation into formulation, mixture, or reaction
product, the Drum Loading and Unloading Release and Inhalation Exposure Model was used to
estimate the airborne concentration associated with generic chemical loading scenarios at industrial
facilities. Specific uncertainties associated with this model are described below:
• The model estimates lugili\c emissions using ill c EPA/OAQPS AP-42 Loading Model. The
applicability of the emission factors used in this model to NMP is not known.
• l-IW assigned statistical distributions based on available literature data or professional judgment
to address the variability in Ventilation Rate (Q), Mixing Factor (k), Vapor Saturation Factor (f),
and Imposed Working Years per Lifetime (WY). The selected distributions may vary from the
actual distributions.
Model for OccujHiiional Exposures during Aerosol Degreasing of Automotive Brakes
The aerosol degreasing assessment uses a near-field/far-field approach (uncertainties on this approach
are presented below) to model worker exposure. Specific uncertainties associated with the aerosol
degreasing scenario are presented below:
• The model references a CARB study (C/ 300) on brake servicing to estimate use rate and
application frequency of the degreasing product. The brake servicing scenario may not be
representative of the use rates for other aerosol degreasing applications involving NMP;
• Aerosol formulations were taken from available safety data sheets, and some were provided as
ranges. For each Monte Carlo iteration the model selects an NMP concentration within the range
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of concentrations using a uniform distribution. In reality, the NMP concentration in the
formulation may be more consistent than the range provided.
Near-Field/Far-Field Model Framework
The near-field/far-field approach is used as a framework to model inhalation exposure for aerosol
degreasing. The following describe uncertainties and simplifying assumptions generally associated with
this modeling approach:
• There is some degree of uncertainty associated with each model input parameter. In general, the
model inputs were determined based on review of available literature. Where the distribution of
the input parameter is known, a distribution is assigned to capture uncertainty in the Monte Carlo
analysis. Where the distribution is unknown, a uniform distribution is often used. The use of a
uniform distribution will capture the low-end and high-end values bul may not accurately reflect
actual distribution of the input parameters.
• The model assumes the near-field and far-field arc well mixed, such thai each zone can be
approximated by a single, average concentration
• All emissions from the facility are assumed to enter the near-Held. This assumption will
overestimate exposures and risks in facilities where some emissions do not enter the airspaces
relevant to worker exposure modeling.
• The exposure models estimate airborne concentrations l-\posines are calculated by assuming
workers spend the entire activity duration in their respective exposure zones (i.e., the worker in
the near-field and the occupational non-user in the far-field). A worker may walk away from the
near-field during part of the process. As such, assuming the worker is exposed at the near-field
concentration for the entire activity duration may overestimate exposure.
• The exposure models represent model workplace settings for NMP used in aerosol degreasing of
automotive brakes The model has not been regressed or fitted with monitoring data.
2.4,2 Consumer Kxposures
NMP is found in consumer products that are a\ ai lahle for purchase at retail stores or via the internet
(Abt •j ). Use of these products can result in consumer exposures. As presented in the previous 2015
EPA NMP Paint Remo\ cr Risk Assessment, women of child-bearing age and pregnant women are the
populations identified as at risk due to the hazards of NMP and exposures. That is, the hazard endpoint,
identified in the Paint Remover Risk Assessment and confirmed in this Risk Evaluation affects the fetus,
and could present a risk to women of child-bearing age or pregnant women (see Section 3.2 and (
EPA. 2015V)
2.4.2.1 ( 'onsunier Exposures Approach and Methodology
EPA selected currently a\ ailable NMP-containing consumer products for exposure analysis that had
uses covered under the Toxic Substances Control Act (see Table 2-68). EPA recognizes that there are
numerous other products containing NMP which are not subject to TSCA, as noted in the NMP Problem
Formulation. For example, NMP is found in cosmetics and pharmaceutical manufacture which are
regulated by the Food and Drug Administration and in pesticides (as an inert ingredient) regulated by
EPA but under the Federal Insecticide Fungicide and Rodenticide Act. EPA also confirmed in the NMP
Market Profile previous uses of NMP-containing products that are no longer in use such as a component
of the inner layer of aluminum aerosol or spray cans used for hairspray or air fresheners and which are
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not based in EPA's professional judgement a reasonably foreseen use (EP A-HQ-OPPT-2016-0743-
0070s) (AM.: ).
Table 2-68. Conditions of Use for Consumer Products Containing NMP
Uange of Product
NMP W eight
Consumer Conditions of I se
I'orin
No. of Products Identified 11
Iractions1'(%)
Sealants
Liquid
3
p
O J
I
o
Adhesives
Liquid
1
X5 i)
Adhesives Remover
Liquid
5
1 i) O0.0
Auto Interior Cleaner
Liquid
1
' J\
O
Auto Interior Spray Cleaner
Aerosol
1
1.0
Cleaners/ Degreasers
Liquid
8
1.0 IDO.O
Engine Cleaner/ Degreaser
Liquid
1
15.0 400
Paint
Liquid
1.0-7.0
Paint Removers
Liquid
35
25.0 - 50.0C
Spray Lubricant (Mold release)
Aerosol
1
30.0-40.0
Stains, Varnishes
Liquid
10
1.0-10.0
Arts and Crafts
Liquid
2
o
l
o
aThe number of products identified is based on the product lisis in EPA's 2u| ~ Markc
a nd Use Report and
Preliminary Information on Manufacturing, Processiim. Disirihiiiioii. 1 se and Disposal N-Methyl-2-
pyrrolidone, as well as the 2016 Supplemental Consumer 1 Aposurc and Risk Estimation Technical Report for
NMP in Paint and Coating Removal.
b Conditions of use with one value for weight fraction represent one product u illi a single value listed in the
Manufacturer's Safety Data Sheet (MSI )S i Several maim lac liner's hsi a rauue of possible NMP weight
fractions within a given product's MSI )S
0 See the 2015 Paint Remover's Risk \ssessmeiil
EPA searched the National Institutes of Health (NIH) 1 lousehold Products Database, various
government and trade association sources for products containing NMP, company websites for product
Safety Data Sheets (SI)Ss) and the internet in general. Lists of consumer products were compiled and
are found in EPA's 2<> I 7 Market Profile ( 2ul'/). These products ranging from 0.1 to >85 weight
percent NMP were categorized according lo llieir respective condition(s) of use and were included in
this drafl risk evaluation.
In the absence of a\ ailable emissions and monitoring data for use of consumer products containing
NMP, a modeling approach was utilized to assess consumer exposure. Appropriate use scenarios
corresponding to the product use were selected for exposure modeling and parameterization of model
inputs used consumer snr\ ey data where appropriate.
The PBPK model was used to derive internal exposure estimates for consumer acute exposures. The
PBPK model required a set of input parameters related to exposure by the dermal and inhalations routes:
NMP weight fraction in the liquid product;
Total skin surface area of hands in contact with the liquid product;
Duration of dermal contact with the liquid product;
Air concentration for inhalation and vapor-through-skin exposure; and
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3029 • Body weight of the exposed consumer/user.
3030
3031 Section 2.4.2.4 presents the input parameters in more detail. The specific PBPK model inputs and
3032 outputs are found in the NMP supplemental documents ( i019e).
3033 EPA relied on information gathered through literature searches and data evaluation (See Section 1.5
3034 above). In addition to product specific data from gray literature, surveys provided data needed to
3035 parameterize model inputs. Many of the model defaults are based on data from EPA's 2011 Exposure
3036 Factors Handbook (see Consumer Exposure Model guide) but were supplemented with data found from
3037 scientific literature ( 017a). For the NMP consumer exposure assessment, existing
3038 assessments such as the 2015 U.S. EPA Paint Remover Risk Assessment and other assessments as listed
3039 in Table 2-68 also provided supplementary information and data.
3040 Table 2-69 lists some of the key sources of information evaluated under the data e\ alualion process and
3041 used in the consumer exposure assessment. A description of the evaluation metrics and confidence
3042 scores for each of the sources is presented in the NMP supplemental document Risk Evaluation for N-
3043 Methylpyrrolidone, Systematic Review Supplemental File: Data Quality Evaluation of( "onsumer and
3044 General Population Studies ( ). The one indoor air monitoring study is discussed below
3045 in Section 2.4.2.5 under consumer use of paint remo\ eis
3046 Table 2-69. Consumer Exposures Assessment Literature Sources
Source Reference
Data Type
( onridence Rating
( la)
SuiAcy Data
Medium (1.8)
( )
Survey Data
High (1.3)
(A.bl 19' )
Survey Data
Medium (1.8)
(Danish Minisuv ui u
Environment 2015)
Completed Assessments
High (1.5)
( )
Completed Assessments
High (1.6)
(• A )
Completed Assessments
High (1.0)
(Ei :nt Canada. 2 )
Completed Assessments
High (1.5)
( iQ94)
Monitoring
Low (2.5)
3047
3048 2.4.2.2 Kxposure Routes
3049 Based on reasonably a\ ailahlc information on the toxicity profile and physicochemical properties of
3050 NMP as well as the previous NMP Paint Remover Risk Assessment, the primary routes of exposure for
3051 human health concerns are dermal, including vapor through skin, and inhalation exposures.
3052 Oral
3053 EPA considered the oral pathway for consumers based on children's exposure potential via mouthing
3054 articles containing NMP (WSDE. 2014). EPA reviewed several NMP assessments (see Table 2-69
3055 above), including a Danish assessment specific to consumer product mouthing and NMP migration.
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Based on an estimated NMP migration amount of 200jig, the Danish study concluded that NMP from
articles such as toothbrushes do not pose a risk ( MM).
Using the Consumer Exposure Model, EPA estimated the exposure to NMP due to mouthing of fabric
articles such as blankets, dolls, or stuffed animals to young children. EPA evaluated NMP exposure for
3 lifestages, infant (<1 year), infant (1-2 years), and small child (3-5 years) (see Table 2-70). Infants
younger than one year would have the greatest possible exposure via mouthing, however levels of 15[j.g
are significantly less than the migration amount reported in the Danish study and well below the oral
dose of 48mg/kg/day that could result in risk. EPA did not further analyze NMP exposure via the oral
pathway in this risk evaluation.
Table 2-70. NMP Oral Exposure to Children via Mouthing
Ueceptor
l-'ahric: blanket,
doll. sluHc(l
animal
(weight Traction)
Mouthing
Duration
(mill)
Body
Weight (kg)
Acute Dose
Kate
(mg/kg/dav)
Infant (<1 year)
1.0E-03
22.5
7.8
1.5E-02
Infant (1-2 years)
1.0E-03
22.5
\Zb
9.2E-03
Small child (3-5 years)
1.0E-03
22.5
18.6
6.2E-03
Dermal
NMP has unique physicochemical properties such lhal il is \ ci v efficiently dermally absorbed. Dermal
absorption was characterized for consumers as it was characterized in the previous NMP Paint Remover
Risk Assessment most importantly in that consumers were assumed not to wear gloves when using
NMP-containing products. For the consumer exposure evaluation, dermal absorption is an important
route of NMP exposure for consumers
NMP exposure to consumers \ ia \ apor through skin uptake was also considered for each of the
scenarios This pathway will most likely occur in the scenario where the product is spray applied.
Inhalation
For each of the product use scenarios except for paint removers, the air concentrations of NMP resulting
from consumer use were modeled using l-PA's Consumer Exposure Model (CEM). For paint removers,
the Paint Remo\ er Risk Assessment estimated air concentrations using the MCCEM model. This model
requires NMP emission data for the specific product and use conditions which was available through the
specific paint remo\ er study et al. 1990). The PBPK model was used to estimate aggregate
dermal, vapor through skin and inhalation exposures resulting from the uses of NMP (See Section
3.2.5.5 below and U.S I [PA (2015) for details of the PBPK model).
Based on anticipated use patterns of each of the product categories by consumers in residential settings,
acute exposures via the dermal and inhalation routes were the primary scenarios of interest. EPA
assumed that consumer users would be females of childbearing age (>16 and older), because, in terms of
hazard, they are the most sensitive subpopulation. Other individuals, adults and children alike may be
exposed via inhalation as bystanders located in the same building as the user of the NMP-containing
consumer product. According to the 2015 Paint Remover risk assessment as well as the supplemental
analysis presented in Section 2.4.2.5, bystanders or non-users are significantly less affected than the
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direct users of the product since they do not have direct dermal contact (U.S. EPA. 2015). Bystander
exposure was evaluated in this risk assessment for two high-end scenarios. Since monitoring data is not
available for most of the consumer product use scenarios, CEM was used to estimate air concentrations
in the breathing zone of the user. These estimates were then used to predict acute inhalation exposure to
NMP for the user using the PBPK modeling approaches.
2.4.2.3 Overview of Models used in Consumer Exposure Estimates
The Consumer Exposure Module (CEM') was selected for the consumer exposure modeling as the most
appropriate model to use due to the lack of available emissions and monitoring data for NMP uses other
than paint removers under consideration. Moreover, EPA did not have the input parameter data from
specific NMP product chamber studies required to run more complex indoor air models for the
consumer products under the scope of this assessment. Details of the i J model and the advantages of
using CEM in estimating consumer exposures to NMP are presented in Appendix I
Modeling Dermal Exposure
Since consumers do not always wear gloves when using consumer products, EPA modeled dermal
exposures for all NMP-containing products. Though CIcan estimate dermal exposures using a
chemical permeability coefficient, EPA used the PBPK model lo estimate the internal dose of NMP as it
is absorbed through the skin both from direct contact of the liquid product and through absorption of
vapor through skin. The PBPK model thus estimated the peak internal dose of NMP through combined
routes of exposure: inhalation, dermal and \ apor through skin and was also used to estimate exposures
in the Paint Remover Risk Assessment.
2.4.2.4 Consumer Model Scenario and Input Parameters for Exposure to Specific
NMP Uses
Table 2-71 describes the models and input parameters lor women of child-bearing age that EPA
evaluated in the NMP consumer exposure assessment. As indicated in Section 2.4.2.2, EPA assessed
dermal and inhalation as the main exposure pathways.
Table 2-71. Product I se Input Parameters for ( KM Modeling
Parameter
1 nils
Value / Description
('MIMICAL PUOPI U I II S
Chemical of Interest
n/a
N -m ethyl -2-py rroli done
CAS Number
n/a
872-50-4
Vapor Pressure
torr
0.345
Molecular Weight
g/mol
99.1
Chemical Saturation
Concentration in Air
mg/m3
1840
Log Octanol-Water
Partition Coefficient
n/a
0.38
Water Solubility
mg/mL
1000
Henry's Law
Coefficient
atm/M
3.2E-09
Gas Phase Mass
Transfer Coefficient
m/hr
CEM estimate, if applicable
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PsimmcU'i-
I nils
Value / Description
MODII. SELECTION / SCENARIO LNPLTS
Inhalation Model
n/a
PBPK
Dermal Model
n/a
PBPK
Emission Rate
n/a
Let CEM Estimate Emission Rate
Product User (s)
n/a
Women of Childbearing age: Adults (>21 years) and Young
women/youth (Ages 16-20 years)
Activity Pattern
n/a
"Stay at home": user spends most of their time at home (i.e.,
includes room of use as well as indoor outdoor user locations
within a 24hr time period)
Product Use Start Time
n/a
9:00 AM
Background
Concentration
mg/m3
0
PRODUCT/ARTICLE PROPERTIES
Frequency of Use
(Acute)
events/day
Fixed at 1 event/day (CIA1 default)
Aerosol Fraction
-
CEM default (0.06)
Product Dilution Factor
unitless
1 i\ed at 1 (i e . no dilution)
ENVIRONMENT INPUTS
Building Volume
(Residence)
m3
492
Air Exchange Rate,
Zone 1 (Residence)
hr1
CEM default
Air Exchange Rate.
Zone 2 (Residence)
hi"1
CI AI default
Air Exchange Rate,
Near-Field Boundary
hi"1
CIAI default (402)
Interzone Ventilation
Rate
nr hr
CEM default
RECEPTOR EXPOSLRi: 1 ACTORS
Body Weight
ku
74 (Adult Women) and 65.9 (Women/Youth 16-20 years)
Averaging Time
vis lifetime
Acute: 1 day
Inhalation Rate-Din inu
Use
mJ/hr
0.67 (Adult and Youth 16-20 years)
Inhalation Rate-Aflei'
Use
m3/hr
0.635 (Adult) and 0.57 (Youth 16-20 years)
Dermal Surface Area
cm2
445 (Adult) and 415 (Youth 16-20 years)
3118
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3119 Table 2-72. Consumer Conditions of Use and Modeling Input Parameters
Consumer
Conditions of
I se
Form
Selected l.S. KI'A (1987)
Survev Scenario 1
Uoom of I se 2
Duration of I se
(mill)'-4
Mass of Product I sed
("•|oz|)5
10th 50th 95th
10th 50th 95th
Adhesives and
Sealants
Liquid
Contact Cement, Super
Glues, and Spray
Adhesives
Bathroom/ Utility
Room/ Outdoors
0 33
4.25
60
0.92
[0.03]
7.69
[0.25]
132.87
[4.32]
Adhesives
Remover
Liquid
Adhesive Removers
Utility Room
3
60
4Ki)
17.85
[0.67]
213.17
[8]
1705.33
[64]
Auto Interior
Cleaner
Liquid
Solvent-type Cleaning
Fluids or Degreasers
Automobile
:
15
12D
16.56
10.56]
96.11
[3.25]
946.35
[32]
Auto Interior
Spray Cleaner
Aerosol
Solvent-type Cleaning
Fluids or Degreasers
Automobile
2
15
120
16.60
[0.56]
96.34
T3.25]
946.53
T32]
Cleaners/
Degreasers
Liquid
Solvent-type Cleaning
Fluids or Degreasers
I lilily Room
2
15
120
16.23
[0.56]
94.19
[3.25]
927.43
[32]
Engine Cleaner/
Degreaser
Liquid
Engine Cleaners/
Degreasers
Garage
5
15
120
73.15
[2.91]
291.60
[11.60]
1206.60
[48]
Paint
Liquid
Latex Paint
Garage
30
180
810
349.63
[10.67]
4194.24
[128]
23068.3
1
T704]
Paint Removers
Liquid
Paint Remo\ or snr\ cy data
from Abl. I'W2
Bathroom/1 lilily
—
90
396
—
540
1,944
Spray Lubricant
(Mold release)
Aerosol
Other Lubricants (\on-
Aulomoli\ e)
I lilily Room
0.08
2
30
3.40
[0.10]
18.71
[0.55]
170.05
[5.00]
Stains,
Varnishes
Liquid
Stains, Varnishes, and
Finishes
1 ,i\ ing Room
10
60
360
61.07
[2.00]
366.42
[12.00]
3908.44
[128.00]
Arts and Crafts
Liquid
l.alex Paint
Utility Room
30
180
810
5.44
[0.17]
65.27
[2.00]
358.98
[11.00]
3120 1 The U.S. EPA 1987 Survey was used to inform \ allies used lor dinalion of use and mass of product used. Where exact matches for conditions of use were not available,
3121 scenario selection was based on product categories ilini Ivsi met the description and usage patterns of the identified consumer conditions of use.
3122 2 The room of use was a selection within the Consumer I \posure Model to model the most likely location of the consumer product use and exposure.
3123 3 Duration of use is time of use per event and assumes only one use per day.
3124 4 Low-end durations of use reported by U.S.EPA 1987 that are less than 0.5 minutes are modeled as being equal to 0.5 minutes due to that being the minimum timestep
3125 available within the model.
3126 5 Mass of product used within U.S.EPA 1987 for given scenarios is reported in ounces but were converted to grams using reported densities in the product SDSs or MSDSs.
Page 145 of 487
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3127
3128
3129
3130
3131
3132
3133
3134
3135
3136
3137
3138
3139
3140
3141
3142
3143
3144
3145
3146
3147
3148
3149
3150
3151
3152
3153
3154
3155
3156
3157
3158
3159
3160
3161
3162
3163
3164
3165
3166
3167
3168
3169
3170
3171
PEER REVIEW DRAFT, DO NOT CITE OR QUOTE
To estimate exposures to these products, numerous input parameters are required to generate a single
exposure estimate. These parameters include the characteristics of the house, the behavior of the
consumer and the emission rate of the chemical into the room of use. In the absence of measured values
for many of the needed inputs, the CEM modeling for NMP used a combination of upper (95th)
percentile, mean, and median as well as low-end (10th percentile) input parameters and assumptions in
the calculation of potential exposure for consumer users. The 10th percentile, 50th percentile and 95th
percentile inputs parameters were selected for three parameters that varied among users and were
included in the 1987 Westat survey, that is, duration of product use, mass of product used, and weight
fraction. This approach represents high-intensity use (95th percentile) in u liich the user uses a greater
amount, higher NMP concentration product for a longer duration and a moderate intensity use (50th
percentile weight fraction/duration/mass used) and produces acute inhalation estimates that are
hypothetical but representative of the range of consumer product use. The general input parameters and
assumptions are summarized in Table 2-71. The input values specific to each use scenario are
summarized and explained more fully in Table 2-72. Based on the previous NMP Paint Kemover Risk
Assessment, the combinations of input parameters associated with low intensity use did not result in
risk. Thus, for this evaluation, only the medium intensily and high intensity use scenarios were further
analyzed. The general input parameters and assumptions are summarized in Table 2-71. The input
values specific to each use scenario are summarized and explained more fully in Table 2-72.
Consumer behavior pattern parameters in ^ include the mass of product used, the duration of use
and the frequency of use. Although the default \ allies in -"I. > for these consumer behavior parameters
are set to high end values, they were not used in this risk assessment. The other parameters (e.g., house
volume) in CEM are set to mean or median values obtained from the literature. A combination of high
end and mean or median values was utilized to produce high end acute inhalation exposure estimates,
whereas a combination of mean and median values was used to produce central tendency acute
inhalation exposure estimates
To determine the appropriateness of the consumer behavior pattern parameters chosen in this risk
evaluation, EPA examined the consumer categories available in the Westat ( 7) survey.
The authors of the Westat ( ) sur\ e\ contacted thousands of Americans to gather
information on consumer behavior patterns related to product categories that may contain halogenated
solvents. The Westat ( ) survey data aligned reasonably well with the description of the
products that were used in this consumer exposure assessment. The data informed the values that EPA
used for the mass of product used, and the time spent in the room of use when considering all surveyed
individuals who identified as users of spray adhesives, spot removers, engine cleaners, brake cleaners or
electronics cleaners
The input parameter for house volume was taken from the Exposure Factors Handbook (2011). The
room volume for aerosol spray adhesives and aerosol spot removers was calculated as a proxy utility
room measuring 9 ft x 10 ft, with 8 ft ceilings ( 014). The designated room of use modeled
for aerosol degreasers and cleaners (used as engine degreasers and brake cleaners) was the garage since
users surveyed in the Westat ( 7) report reported use in the garage. The CEM model does
not include a garage volume in its default room parameters, thus the median garage volume from a 2007
indoor air quality study (Batterman et ai. 2007) of 15 homes in Michigan was used as a reasonable
proxy value. The room of use for adhesives was reported in the product sheet as outdoors. Since CEM
does not have an outdoors scenario, the garage was selected as the room of use but input parameters
such as a high air exchange rate were modified to simulate the outdoors.
Page 146 of 487
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PEER REVIEW DRAFT, DO NOT CITE OR QUOTE
3172 The user's body weight, inhalation rate, and inside of two hands surface area were set to adult (+21) and
3173 teen (16-20) women mean or the median values from the Exposure Factors Handbook ( 11)
3174 for the simulations used in this assessment.
3175 The air exchange rate in the room of use does not take into consideration open windows or the use of an
3176 exhaust fan. While it is possible that some users may employ these exposure reduction techniques inside
3177 their homes, the goal of the consumer exposure assessment was to provide an acute exposure estimate
3178 for ventilation conditions representing average household air exchange rates. Moreover, residential users
3179 would not necessarily have the type of indoor exposure reduction tools/equipment (e.g., gloves, exhaust
3180 ventilation) that workers are likely to have in occupational settings. Consumers may not necessarily be
3181 as aware of potential chemical hazards as workers and would not have a standard operating procedure in
3182 place to assure that they use exposure reduction techniques each time they use a product.
3183 In this assessment it was assumed that there was no pre-existing concentration of WIP in the home
3184 before product use began. The outdoor air was also assumed to be free of NMP, meaning thatthe air
3185 exchange rate described the intake of air with no pre-existing NMP contamination.
3186 The products were assumed to be brushed on as a liquid to \ ar\ ing surfaces, where a thin film of the
3187 product was assumed to build up, evaporate, and contribute to the ai r concentration of the chemical in
3188 the room. EPA relied on modeled emission rates because data from chamber studies were not available.
3189 To generate emission rates, CEM used empirical data from studies assessing the emission rates of pure
3190 solvents (DTIC. 1981). CEM used the Chinn study as surrogate data to calculate the rate of evaporation
3191 of NMP from the surface to the air in the home.
3192 The use of an exponentially decaying emission rate for NMP from the application surface was based on
3193 vapor pressure and molecular weight the equations using the Chinn method. The adhesive application
3194 should be well modeled by the Chinn study since it contained over 85% NMP. On the other hand, the
3195 spray cleaner product may ha\ e more components, and the interaction of these chemicals could alter the
3196 evaporation rate of NMP. This introduces uncertainty into the assessment, however EPA did not identify
3197 a better data set available to model the emission rates. Within the current exposure assessment, the 24-hr
3198 exposure was not strongly dependent on the emission rate due to the amount of time the product user
3199 spends in the room of use (see Table 2-72 for details).
3200
3201 2.4.2.5 Consumer Exposure Scenarios
3202 Adhesives and Sealants
3203 Exposure to NMP found in \\l P-containing adhesive and sealant products was based on four products
3204 with associated weight fraction data. Three of the products had a range of weight fractions from 0.1 to
3205 1% and were similar use products, sealants. One product was an adhesive to glue boards used in deck
3206 construction. The duration of use and mass of product used were based on the 1987 Westat survey data,
3207 specifically the data found under the Contact Cement, Super Glues, and Spray Adhesives scenario and
3208 are listed in Table 2-73.
3209 The 'Glues and Adhesives (small scale)' default scenario within the Consumer Exposure Module (CEM)
3210 was chosen for conducting the modeling runs. This selection was the closest match to the liquid
3211 adhesive scenario among the default CEM exposure scenarios. The common modeling inputs required to
Page 147 of 487
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3212
3213
3214
3215
3216
3217
3218
3219
3220
3221
3222
3223
3224
3225
3226
3227
3228
3229
3230
3231
3232
3233
3234
3235
3236
PEER REVIEW DRAFT, DO NOT CITE OR QUOTE
run CEM for all consumer single-use scenarios evaluated in this assessment are provided in Table 2-71.
Table 2-71 also has a brief explanation of the source of each parameter and the justification for the
parameter selection. Other scenario-specific input parameters are provided in Table 2-72.
CEM calculated air concentrations over the course of the simulation for the room of use and the rest of
the house (Zone 1 and Zone 2). These concentrations were inputs to the PBPK model and used the body
weights (74 kg, 65.9 kg), inside both hands surface areas (445 cm2, 415 cm2) and respiration rates (0.74
m3/hr, 0.68 m3/hr during use) for adult women (+21 years) and young women (16-20 years), respectively
and both age groups are considered of child-bearing age in calculating the internal dose of NMP (cite:
EPA definition of Childbearing age). Though both young and adult women scenarios were modeled and
are presented in Appendix 1.2, the difference in exposures were very small I -\posures to adult women
are presented below as they are expected to adequately represent the women (if child-bearing age who
may use these consumer products.
Table 2-73 presents the results of the indoor air concentrations (ppm) for both cenlial tendency and high
end estimated exposures for the consumer use scenarios hascd on the 50lh percentile and 95th percentile
input parameters. Calculations detailing the conversion from acute dose rates to air concentrations are
provided in a supplemental Excel spreadsheet file. (I .S * > *, ^01?u)
Table 2-73. Estimated3 NMP Air Concentrations (Time Averaged Over 1 Day) Based on
Residential Use of Adhesives or Sealants
Scenario Description
For Product I ser
(Women of
Childhearing Age)
Duration
of I se
(mill)
Weight
Fraction
(%)
Mass of
Product
I sed («)
Air Concentration 11
Max 8 In
TWA
(nig/nr*)
Max 8 In
TWA
(ppm)
Max 24 lir
TWA
(ppm)
Sealant
Medium Intensity Use b
4 25
0.77
7.69
4.30E-02
1.06E-02
3.76E-03
High Intensity Use c
60
0.77
132.87
6.18E-01
1.52E-01
5.56E-02
Adhesive
Medium Intensity Useb
4.25
85
7.69
1.82E-01
4.48E-02
1.49E-02
High Intensity I se c
60
85
132.87
1.74
0.429
0.143
a See Appendi\ I' lor details about the model inputs and the method used to estimate air concentrations of NMP.
b Medium intensiis use estimate based on using 50th percentile values for use patterns from Westat Survey (1987).
0 High intensity use csiimale ha sod on using 95th percentile values for use patterns from Westat Survey, (1987).
The model output reports the peak concentration of NMP, however this air concentration was not used
in the risk assessment. The peak concentration was the highest concentration among all 10-second time
intervals that CEM simulated within a 24-hr period. The peak concentration may only exist in the room
of use for a short duration and was not considered a good indicator of what the concentration of NMP
would be for longer time periods. Thus, the peak concentration was not used in the risk assessment as it
was not representative of a 24-hr exposure.
Page 148 of 487
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PEER REVIEW DRAFT, DO NOT CITE OR QUOTE
3237 The maximum internal NMP dose (Cmax) resulting from inhalation, dermal and vapor through skin
3238 exposures to women of childbearing age consumer use of adhesive or sealant products as estimated from
3239 the PBPK model is presented in Table 2-74.
3240 Table 2-74. Estimated NMP Exposures (Time Averaged Over 1 Day) Based on Residential Use of
3241 Adhesives or Sealants
Scenario Description
l'"or Product I ser
Women of
Childbearing Age
('max (mg/l.)
Pregnant W omen
('max (mg/l.)
Sealants
Medium Intensity Use
0.011
i)i)| |
High Intensity Use
0.070
0 DOS
Adhesives
Medium Intensity Use
1.238
1.203
High Intensity Use
5.623
5.385
3242
3243 Adhesives Removers
3244 Exposure to NMP found in NMP-containinu adhesi\ e remo\ or products uas based on five products with
3245 associated weight fraction data. Weight fractions ranged from 1° 0 to 6<)".. and were similar use products.
3246 The duration of use and mass of product used were bused on the 1987 Westat survey data, specifically
3247 the data found under the Adhesive Removers scenario and are listed in Table 2-75.
3248 Table 2-75. Estimated3 MM P Air Concentrations (Time Averaged Over 1 Day) Based on
3249 Residential Use of Adhesives Uemovers
Scenario Description
l-'or Product I ser
(Women of
Childbearing Age)
Duration
of I se
(mill)
Weight
l-'raction
<%)
Mass of
Product
I sed (g)
Air Concentration 11
Max 8 In
TWA
(mg/ni')
Max S In
TWA
(ppni)
Max 24 lir
TWA
(ppm)
. Ulliesive Remover
Medium Intensity Use'
(•>t)
18.90
213.17
1.42
0.349
0.119
High Intensity Use b
4XO
25.00
1,705.33
21.70
5.34
1.89
a See Appendix F lor details aboin I lie model inputs and the method used to estimate air concentrations of NMP.
b Medium intensity use csiiiuatc ha sal on using 50th percentile values for use patterns from Westat Survey (1987").
c High intensity use estimate hased on usinu 90th percentile values for use patterns from Westat Survey, (1987).
3250
3251 The ' Adhesives/Caulk Removers' default scenario within the Consumer Exposure Module (CEM) was
3252 chosen for conducting the modeling runs. This selection was the closest match to the liquid adhesive
3253 remover scenario among the default CEM exposure scenarios. The common modeling inputs required to
3254 run CEM for all consumer scenarios evaluated in this assessment are provided in Table 2-71. Other
3255 scenario-specific input parameters are provided in Table 2-72.
Page 149 of 487
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PEER REVIEW DRAFT, DO NOT CITE OR QUOTE
3256 CEM calculated air concentrations over the course of the simulation for the room of use and the rest of
3257 the house (Zone 1 and Zone 2). These concentrations were inputs to the PBPK model and used the body
3258 weight and respiration rate for adult women (+21) and young women (16-20) both considered of child-
3259 bearing age in calculating the internal dose of NMP.
3260 Table 2-75 presents the results of the indoor air concentrations (ppm) both central tendency and high-
3261 end estimated exposures for the consumer use scenarios based on the 50th percentile and 95th percentile
3262 input parameters. Calculations detailing the conversion from acute dose rales lo air concentrations are
3263 provided in a supplemental Excel spreadsheet file. ( )
3264 Detailed CEM modeling results are provided in Table 2-72.
3265 Total internal NMP dose (Cmax) resulting from inhalation, dermal and vapor through skin exposures to
3266 women of childbearing age consumer use of adhesh e remo\ er products as estimated from the PBPK
3267 model is presented in Table 2-76.
3268 Table 2-76. Estimated NMP Exposures (Time Averaged Over I Day) Based on Residential Use of
3269 Adhesive Removers
Scenario Description
Kor Product I ser
W omen of
(hildhearing Age
('max (mg/1.)
Pregnant W omen
('max (mg/1.)
Adhesive Removers
Medium Intensity Use
1.292
1.239
High Intensity Use
5.957
5.778
3270
3271 Auto Interior Liquid and Spray Cleaners
3272 Exposure to NMP found in NMP-containinu auto interior cleaner products was based on one product
3273 that was a liquid and one product that was a spray applied. The NMP weight fraction of the liquid
3274 cleaner was listed in the product Safety Data Sheet as a range between 1 and 5%. For the modeling
3275 scenarios. F.PA assumed a typical or central tendency NMP amount of 3% and at a high-end of 5%
3276 NMP. The duration of use and mass of product used were based on the 1987 Westat survey data,
3277 specifically the data found under the Solvent-type Cleaning Fluids or Degreasers scenario and are listed
3278 in Table 2-77.
3279 For the spray applied cleaner, the product data sheet listed the weight fraction as <1%. EPA
3280 conservatively used I".. Ibr both scenarios with the other two parameters distinguishing the scenarios as
3281 either high-end or central tendency. The duration of use and mass of product used were based on the
3282 1987 Westat survey data, specifically the data found under the Solvent-type Cleaning Fluids or
3283 Degreasers scenario and are listed in Table 2-77.
Page 150 of 487
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PEER REVIEW DRAFT, DO NOT CITE OR QUOTE
3284 Table 2-77. Estimated3 NMP Air Concentrations (Time Averaged Over 1 Day) Based on
3285 Residential Use of Auto Interior Liquid or Spray Cleaners
Scenario Description
l-'or Product I ser
(Women of
Childhearing Age)
Air Concentration 11
Duration
of I se
(mill)
Weight
l-'raction
(%)
Mass of
Product
I sed (g)
Max S In
TWA
(nig/in')
Max 8 lir
TWA
(ppm)
Max 24 lir
TWA
(ppm)
Auto Interior Liquid Cleaner
Medium Intensity Useb
15
3
7.69
: ss
i) 711
0.237
High Intensity Usec
120
5
132.87
54 4
13.4
4.48
Auto Interior Spray Cleaner
Medium Intensity Useb
15
1
7 W
10.8
() Zoo
8.89E-02
High Intensity Usec
120
1
132.87
12.0
2.95
0.984
a See Appendix F for details about the model inputs and the method used u> csiiinalc air concentrations of NMP.
b Medium intensity use estimate based on using 50th percentile values for use patterns from Westat Survey (jj_2£7).
c High intensity use estimate based on using 95th percentile values lor use n;illcrus liom Westat Survey, (1987).
3286
3287 The 'All Purpose Liquid Cleaner' and the 'All Purpose Spray Cleaner" default scenarios within the
3288 Consumer Exposure Module (CEM) were chosen for conducting the modeling runs for the Auto Liquid
3289 Cleaner and Auto Spray Cleaner scenarios. This selection was the closest match to the liquid or spray
3290 cleaner scenario among the default CI-VI exposure scenarios. The common modeling inputs required to
3291 run CEM for all consumer scenarios e\ aluated in this assessment are provided in Table 2-71. Other
3292 scenario-specific input parameters are provided in Table 2-72.
3293 CEM calculated air concentrations o\ er the course of the simulation for the room of use and the rest of
3294 the house (Zone 1 and /one 2) These concentrations were inputs to the PBPK model and used the body
3295 weight and respiration rate lor adult women (+21) and young women (16-20) both considered of child-
3296 bearing age in calculating the internal dose of NMP (cite EPA definition of childbearing age).
3297 Table 2-77 presents the results of the indoor air concentrations (ppm) both central tendency and high-
3298 end estimated exposures for the consumer use scenarios based on the 50th percentile and 95th percentile
3299 input parameters Calculations detailing the conversion from acute dose rates to air concentrations are
3300 provided in a supplemental Excel spreadsheet file. (U.S. EPA. 2019d)
3301 Total internal NMP dose K'max) resulting from inhalation, dermal and vapor through skin exposures to
3302 women of childbearing age consumer use of various auto interior cleaner products as estimated from the
3303 PBPK model is presented in Table 2-78.
Page 151 of 487
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PEER REVIEW DRAFT, DO NOT CITE OR QUOTE
3304 Table 2-78. Estimated NMP Exposures (Time Averaged Over 1 Day) Based on Residential Use of
3305 Auto Interior Liquid or Spray Cleaners
Scenario Description
l'"or Product I ser
W omen of
(liildhcaring Age
('max (mg/1.)
Pregnant W omen
('max (mg/1.)
Auto Interior Liquid Cleaner
Medium Intensity Use
0.256
0.249
High Intensity Use
4.355
4.245
Auto Interior Spray Cleaner
Medium Intensity Use
0.093
0.091
High Intensity Use
0.183
0.177
3306
3307 Cleaners/Degreasers, Engine Cleaner/Degreaser and Spray Lubricant
3308 Exposure to NMP found in consumer cleaner/degreaser and spray kihi icant products containing NMP
3309 was based on product data found on a total of 10 products. Eight products ranging from oven cleaners to
3310 metal cleaners to resin cleaner had NMP weight fractions, as listed in the product Safety Data Sheets,
3311 between 1% and 100%. The duration of use and mass of product used u ere based on the 1987 Westat
3312 survey data, specifically the data found under the Sol\ cut-type Cleaning fluids or Degreasers scenario
3313 and are listed in Table 2-79.
3314 One product was specifically used as an engine cleaner (weight fraction between 15% and 40%) and one
3315 product was found as a spray luhricant (weight fraction between 30% to 40%). For the three modeling
3316 scenarios, EPA assumed the product could be available in a low-end formulation with 1% NMP, a
3317 typical or central tendency amount of 3% and at a high-end of 5% NMP. The duration of use and mass
3318 of product used were based on the 1987 Westat sur\ ey data, specifically the data found under the Engine
3319 Cleaners/Degreasers scenario and are listed in Table 2-79.
3320 One product was identified as a mold release (i.e., once a product is formed or shaped then hardened in a
3321 mold, it then can be easily remo\ ed). It was modeled differently since it is used as a spray product. The
3322 duration of use and mass of product used were based on the 1987 Westat survey data, specifically the
3323 data found under the Other I .uln icants scenario and are listed in Table 2-79.
Page 152 of 487
-------
3324
3325
3326
3327
3328
3329
3330
3331
3332
3333
3334
3335
3336
3337
3338
3339
3340
3341
3342
3343
3344
PEER REVIEW DRAFT, DO NOT CITE OR QUOTE
Table 2-79. Estimated3 NMP Air Concentrations (Time Averaged Over 1 Day) Based on
Residential Use of Cleaners/Degreasers. Engine Cleaner/Degreaser and Spray Lubricant
Scenario Description
l-'or Product I ser
(Women of
Childbcaring Age)
Duration
of I se
(mill)
\Y'eight
l-'raction
(%)
Mass of
Product
I sed (g)
Air Concentration 11
Max S In
TWA
(nig/nr')
Max S In
TWA
(ppm)
Max 24 lir
TWA
(ppm)
Cleaners/Degreasers
Medium Intensity Use1
15
25.46
94.11)
4.56
1.61
High Intensity Use'
120
29.87
927.43
235
57.9
20.8
Engine Cleaner/Degreaser
Medium Intensity Use1
15
27.50
:i)i o
39.7
So
3.56
High Intensity Use'
120
40
.Zoo (ii)
281
(•>') 3
25.5
Spray Lubricant
Medium Intensity Use1
35
18.7:
0.28
7.04E-02
2.48E-02
High Intensity Use'
30
4i)
170.05
2.65
0.65
0.23
1 See Appendix F for details about the model inpuis ;md i lie method used to estimate ;iii° concentrations of NMP.
' Medium intensity use estimate based on using 50m percentile \ nines lor use p;iileriis from Westat Survey (1987).
: High intensity use estimate based on using 95th percent: Ic \ ;ilucs lor use pnllcrns from Westat Survey, (1987).
The 'All Purpose Liquid Cleaner". "All Purpose Spray Cleaner' and 'Lubricant (spray)' default scenarios
within the Consumer l-xposure Module ( CLM) were chosen for conducting the modeling runs for the
Cleaner/Degreaser, Engine Cleaner Degreaser and Spray Lubricant scenarios, respectively. This
selection was the closest match to the liquid or spray cleaner scenario among the default CEM exposure
scenarios. The common modeling inputs required to run CEM for all consumer scenarios evaluated in
this assessment are |iro\ ided in TaMe 2-71 Other scenario-specific input parameters are provided in
Table 2-72.
CEM calculated air concentrations over the course of the simulation for the room of use and the rest of
the house (Zone I and Zone 2). These concentrations were inputs to the PBPK model and used the body
weight and respiration rate for adult women (+21) and young women (16-20) both considered of child-
bearing age in calculating the internal dose of NMP.
Table 2-79 presents the results of the indoor air concentrations (ppm) both central tendency and high-
end estimated exposures for the consumer use scenarios based on the 50th percentile and 95th percentile
input parameters. Calculations detailing the conversion from acute dose rates to air concentrations are
provided in a supplemental Excel spreadsheet file. ( 2019d)
The total internal NMP dose (Cmax) resulting from inhalation, dermal and vapor through skin exposures
to women of childbearing age consumer use of various types of cleaner/degreaser products as estimated
from the PBPK model is presented in Table 2-80.
Page 153 of 487
-------
3345
3346
3347
3348
3349
3350
3351
3352
3353
3354
3355
3356
3357
PEER REVIEW DRAFT, DO NOT CITE OR QUOTE
Table 2-80. Estimated NMP Exposures (Time Averaged Over 1 Day) Based on Residential Use of
Scenario Description
l'"or Product I ser
Women of
Childbcaring Age
Cmax (mg/l.)
Prcgnanl W omen
Cmax (mg/l.)
Cleaners/Degreasers
Medium Intensity Use
1.033
1.016
High Intensity Use
13.40
13.DI)
Engine Cleaner/Degreaser
Medium Intensity Use
1.682
1 Mi)
High Intensity Use
16.46
15.97
Spray Lubricant
Medium Intensity Use
0.332
0.322
High Intensity Use
2.853
2 S()|
Paint and Arts and Craft Paint
Exposure to NMP found in consumer painl aiicl ai ls aiicl crafts paint products containing NMP was based
on product data found on a total of four products Two painl products llial contained NMP were paints
such as concrete paint and truck bed coating and had NMP weight fractions ranging from 1% to 7%. For
arts and crafts paint the XMP weight fractions were <> I"., to 1%. The duration of use and mass of
product used were based on the 11>K7 Wcstat survey data, specifically the data found under the Latex
Paint scenario and are listed in TaMe 2-71) For the Arts and Craft scenario mass of product was adjusted
lower (ratio of 64) by the craft \ olunie sold (2 ounces) relative to the wall paint (gallon).
Table 2-81. Estimated" NMP Air Concentrations ( l ime Averaged Over 1 Day) Based on
Residential I se of Painl and Arts and Crafts Paint
Scenario Description
Kor Product I ser
(Women of
Childbcaring Age)
Duration of
I se
(mill)
Weight
l-'raction
(%)
Mass of
Product
I sed (g)
Air Concentration "
Max 8 In
TWA
(nig/nr*)
Max 8 hi
TWA
(ppni)
Max 24 lir
TWA
(ppm)
Paint
Medium Intensity I 'se1'
180
2.03
4,194.24
2.40
0.593
0.204
High Intensity Usec
810
3.63
23,068.31
18.3
4.51
2.52
Arts and Crafts
Medium Intensity Useb
180
0.55
65.30
1.41E-02
3.48E-03
1.19E-03
High Intensity Usec
810
1.00
359.00
1.01E-01
2.48E-02
1.39E-02
a See Appendix F for details about the model inputs and the method used to convert acute dose rates (ADRs) to air
concentrations of NMP.
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Scoiuirio Description
l-or Product I ser
(Women of
( hiltlhe;irin« Ago)
Duration of
I so
(mill)
Weight
l-rnction
(%)
Msiss of
Product
I sod (g)
Air ('onccnlrsilion 11
Msix S hi
TWA
(mg/iir')
M;i\ S hi
TWA
(ppm)
M;ix 24 lir
TWA
(ppm)
'' Medium iiiIciisiiv use estimate hased on using 5<) percentile \ allies for use patterns from Wesial Siiia e\ < i.
c High intensity use estimate based on using 95th percentile values for use patterns from Westat Survey, (1987).
3358
3359 The 'Solvent-based Wall Paint' and the 'Crafting Paint' default scenarios within the Consumer
3360 Exposure Module (CEM) were chosen for conducting the modeling runs lor the Paint and Arts and
3361 Crafts scenarios, respectively. These selections were the closest match lo each of the paint scenarios
3362 among the default CEM exposure scenarios. The common modeling inputs required lo run CEM for all
3363 consumer scenarios evaluated in this assessment are provided in Table 2-71. Other scenario-specific
3364 input parameters are provided in Table 2-72.
3365 CEM calculated air concentrations over the course of the simulation for the room of use and the rest of
3366 the house (Zone 1 and Zone 2). These concentrations were inputs to the PBPK model and used the body
3367 weight and respiration rate for adult women (+21) and young women (16-20) both considered of child-
3368 bearing age in calculating the internal dose of \\l P
3369 Table 2-81 presents the results of the indoor air concentrations (ppm) both central tendency and high-
3370 end estimated exposures for the consumer use scenarios based on the 50lh percentile and 95th percentile
3371 input parameters. Calculations detailing the com ersion from acute dose rates to air concentrations are
3372 provided in a supplemental Excel spreadsheet file ( . ... ..:.).
3373 Detailed CEM modeling results are provided in Table 2-72.
3374 Total internal NMP dose (Cmax) resulting from inhalation, dermal and vapor through skin exposures to
3375 women of childbearinu age consumer use of paint products as estimated from the PBPK model is
3376 presented in Table 2-S2
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Table 2-82. Estimated NMP Exposures (Time Averaged Over 1 Day) Based on Residential Use of
Paints and Arts and Crafts Paints
Scenario Description
l'"or Product I ser
W omen of
Childhcaring Age
Cmax (mg/l.)
Pregnant W omen
Cmax (mg/l.)
Paints
Medium Intensity Use
0.374
0.358
High Intensity Use
1.422
1.41 5
Arts and Crafts Paints
Medium Intensity Use
0.071
0.068
High Intensity Use
0.222
0.219
Stains, Varnishes, Finishes (Coatings)
Exposure to NMP found in consumer stains, varnishes, finishes and oilier coatings products containing
NMP was based on product data found on a total of nine products The NMP weight fractions range was
between 0.3% to 10% with the mean of 4.97% and the average high-end of 8.25% used to model
consumer exposure estimates. The duration of use and mass of product used were based on the 1987
Westat survey data, specifically the data found under the Stains, Varnishes, and Finishes scenario and
are listed in Table 2-83.
The 'Varnishes and Floor Finishes' default scenarios within the Consumer Exposure Module (CEM)
was chosen for conducting the modeling runs for the Stains, Varnishes, Finishes (Coatings) scenario.
This selection was the closest match to the liquid coatings scenario among the default CEM exposure
scenarios. The common modeling inputs required to run CEM for all consumer scenarios evaluated in
this assessment are pro\ ided in Table 2-71 Other scenario-specific input parameters are provided in
Table 2-72.
Table 2-83. Kslimaled11 NMP Air Concentrations ( l ime Averaged Over 1 Day) Based on
Residential I se of Stains. Varnishes. l-'inishes (Coatings)
Scenario Description
Kor Product I ser
(Women of
Childhcaring Age)
Duration
of I se
(mill)
Weight
l-'raction
(%)
Mass of
Product
I sed (g)
Air Concentration "
Max 8 In
TWA
(nig/nr')
Max 8 In
TWA
(ppm)
Max 24 lir
TWA
(ppm)
Stains, Varnishes, Finishes (Coatings)
Medium Intensity Use b
60
4.97
366.42
6.84E-01
1.68E-01
5.74E-02
High Intensity Usec
360
8.25
3,908.44
12.5
3.08
1.08
a See Appendix F for details about the model inputs and the method used to estimate air concentrations of NMP.
b Medium intensity use estimate based on using 50th percentile values for use patterns from Westat Survey (1987).
c High intensity use estimate based on using 95th percentile values for use patterns from Westat Survey, (1987).
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3403
3404
3405
3406
3407
3408
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CEM calculated air concentrations over the course of the simulation for the room of use and the rest of
the house (Zone 1 and Zone 2). These concentrations were inputs to the PBPK model and used the body
weight and respiration rate for adult women (+21) and young women (16-20) both considered of child-
bearing age in calculating the internal dose of NMP.
Table 2-83 presents the results of the indoor air concentrations (ppm) both central tendency and high-
end estimated exposures for the consumer use scenarios based on the 50th percentile and 95th percentile
input parameters. Calculations detailing the conversion from acute dose rales lo air concentrations are
provided in a supplemental Excel spreadsheet file. ( 201 )
Total internal NMP dose (Cmax) resulting from inhalation, dermal and \ apor through skin exposures to
women of childbearing age consumer use of coatings products as esti mated from (he PBPK model is
presented in Table 2-84.
Table 2-84. Estimated NMP Exposures (Time Averaged Over 1 Day) Based on Residential Use of
Scenario Description
l'"or Product I ser
W omen of
(hildhearing Age
('max (m«/l.)
Pregnant W omen
('max (mg/1.)
Stains, Varnishes, Finishes (Coatings)
Medium Intensity Use
0.341
0.327
High Intensity Use
1.947
i ss:
Paint Removers
Consumer exposure to NM P found i n consumer paint remover products containing NMP was assessed
in the Final Paint Remover Risk . \sscssments ( as well as the Supplemental Consumer
Exposure and Risk Est i mat ion Technical Report for NMP in Paint and Coating Removal (see 6F.2). For
the supplemental analysis, exposures were estimated for 18 scenarios. The E2 scenario was selected as a
representative high intensity use scenario The paint remover product was modeled to remove paint from
a bathtub and using 4 applications The \2 scenario was selected as a representative medium intensity
use scenario The NMP paint remover product was used to remove paint from a coffee table. The weight
fraction for paint remover products was 50% for both scenarios. Appendix F.2 lists all of the evaluated
scenarios for the paint remo\ er e\ aluation.
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3420 Table 2-85. Estimated NMP Air Concentrations (Time Averaged Over 1 Day) Based on
3421 Residential Use Paint Removers
Air Concentration
Scenario Description
Kor Product I ser
Duration of
I se
(mill)
Weight
l-'raction
(%)
Mass of
Product
I sed (g)
Max 8 In
TWA
(nig/nr*)
Max 8 In
TWA
(ppm)
Paint Removers
Medium Intensity Use
60
50
54i)
3 24
0.8
High Intensity Use
360
50
1944
146
36.0
3422
3423 As described in detail in the previous assessments, emissions data were available specifically for paint
3424 remover product use. This data can then be used in a higher tier exposure model, the MCCEM to
3425 estimate air concentration. In principle, as in the CEM, llie MCCEM also estimates NMP air
3426 concentrations in various areas of the house depending on Ihe user's activity pattern. MCCEM
3427 calculated air concentrations over the course of the simulation for the room of use and the rest of the
3428 house (Zone 1 and Zone 2). These concentrations were inputs lo the IMiPK model and used the body
3429 weight and respiration rate for adult women of chikl-hcaiing age in calculating the internal dose of
3430 NMP.
3431 Table 2-86 presents the internal dose for women of childhearing age lor the medium intensity use and
3432 high intensity use scenarios
3433 Table 2-86. Estimated NMP Kxposures (Time Averaged Over 1 Day) Based on Residential Use of
3434 Paint Removers
Women orChildbcaring
Scenario Description
Age
Kor Product I ser
('max (mg/l.)
Paint Removers
Medium Intensity Use
2 i)2
High Intensity I sc
10.02
3435
3436 EPA reviewed data from one study that specifically measured NMP air concentrations while an NMP-
3437 containing paint removal product was being used on floors in a house undergoing renovation (Kiefer.
3438 1994). The study reported air concentrations ranging from 3.6 to 7.7 ppm in the room of use. In EPA's
3439 supplemental analysis of NMP use in paint and coating removal, the modeled paint removal use resulted
3440 in air concentrations of 11.1 ppm (8-hr time weighted average). Although this estimated NMP air
3441 concentration is higher than the measured air concentration presented by Kiefer et al. (1994). both
3442 represent the air concentration in the room that a non-user would be exposed to rather than the personal
3443 breathing zone concentration to which the user is directly exposed. EPA determined that the estimated
3444 NMP exposures incurred during floor paint removal do not present a risk to non-users (See Appendix
3445 F.2).
3446
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Exposure to Bystanders
In each of the consumer scenarios listed above, use of a product containing NMP is expected to result in
air concentrations of NMP and user inhalation exposure to NMP in addition to dermal and vapor-
through skin exposures. EPA also expects that the NMP air concentrations can be circulated through the
house via the air ventilation system so that NMP exposures could occur to other occupants in the house
during and after consumer use. The air concentration in Zone 2 (rest of the house) is presented in the
supplemental document, Risk Evaluation for N-Methylpyrrolidone, Supplemental Information on
Consumer Exposure Assessment, Consumer Exposure Model Outputs (U.S. EPA. 2019d).
EPA estimated the internal dose for indirect NMP exposures adull In slanders as well as children aged 3-
5 years due to their location in the house during consumer use (see TaMe 2-S5) ( 2019e).
Table 2-87. Estimated Bystander
Exposure to NMP Consumer I se
livslaiider l-'emale
Bystander Child
Consumer Conditions of I se
Adull Cmax
(3-5 yrs) Cmax
(ins/1.)
(mg/l.)
Cleaners/ Degreasers
4.06
4 70
Engine Cleaner/ Degreaser
5.55
(•> 5 1
2.4.2.6 Key Assumptions siml Confidence
Given the absence of direct measurement and monitoring of consumer exposures during product use,
modeling was used to evaluate consumer exposures resulting from (he conditions of use summarized in
Table 2-72. Modeling requires a number of input parameters, some of which rely on default modeling
assumptions and some of which rely oil user inputs or selections As with any modeling approach, there
are uncertainties associated with the assumptions and data used. An overall review of these factors can
help develop a qualitative description of the confidence associated with the modeling approach and
results.
Key Assumptions
Evaluation of acute consumer exposure is based on the assumption that the products used under the
conditions of use summarized in Table 2-72, except paint removers, are only used once per day. This
assumption considers a single use event u hich may occur over a 24-hour period and represents an
expected consumer use pattern. This is a reasonable assumption for the average intensity user but may
underestimate those high intensity users such as do-it-yourselfers (DIY) that could use a product
multiple times in a day The paint remover scenario as defined in the Paint Remover Risk Assessment,
defines a user pattern in which the product is applied then scraped away with the paint and reapplied
again as is outlined in the product directions. This product-specific use is reflected in the use patterns for
all of the products evaluated for consumer exposures.
Evaluation of consumer exposure for this evaluation is also based on the assumption that a consumer
uses a single product or product type. For the products estimated under the conditions of use, this is a
reasonable assumption. However, this assumption may, in general, underestimate NMP exposures since
NMP is also found in cosmetic products and other personal care products that could be used
concurrently.
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This evaluation assumes consumer exposure is not chronic in nature. This assumption is based on the
expected consumer use pattern and data found during systematic review that indicates frequency of use
(days of use) of products containing the chemical of concern is not chronic in nature. This assumption is
also based on the fairly rapid elimination of NMP so that the use pattern and data would not be chronic
in nature. This assumption may result in excluding certain consumer users who may be do-it-yourselfers.
This evaluation assumes a background concentration of zero for the chemical of concern during
evaluation of consumer exposure. This assumption is primarily driven by the physical chemical
properties of the chemical of concern which is the high vapor pressure and expected quick dissipation of
the chemical of concern.
Inputs
Inputs for the modeling were a combination of physical chemical properties of i lie chemical of concern,
default values within the models used, values from the Exposure Factors Handbook ( IP A. 2.011).
and use pattern survey data found in the literature as pai l of the systematic review process (Westat
Survey (U.S. EPA. 1987)). Physical chemical properties of the chemical of concern are pre-defined and
well established in the literature. These properties do not change under standard conditions and therefore
have high confidence associated with them.
Default values within the models used are a combination of central tendency and high-end values
derived from well-established calculations, modeling, literature, and from the Exposure Factors
Handbook Q v ^ \ < it). The models used have a wide variety of parameters with default values,
although certain default values can be changed (if information and data are available) prior to running
the model. There is a high confidence associated with these values due to the number of parameters
where defaults are available.
Values from the Exposure Factors I landbook ( J .. :LL) are a combination of central tendency
and high-end values which are well established and commonly used for exposure evaluations and
modeling. The values are derived from literature, modeling, calculations, and surveys. There is a high
confidence associated with the l-xposure Factors Handbook (U.S. EPA. 2.011).
The \Yestat Survey ( ) was previously described in this evaluation. It is an EPA-directed
national snr\ e\ which recei\ ed over 4/0> completed questionnaires from across the United States. The
survey aimed to answer multiple questions related to the use of solvent-containing consumer products
within thirty-two different common household product categories. Multiple aspects of the survey and
survey results were utilized in this evaluation. Most of the consumer uses summarized in Table 2-72
aligned well with one of the thirty-two product categories within the Westat Survey. There is a high
confidence associated with cross-walking of consumer uses with the Westat product categories.
The representativeness of the consumer use patterns (duration of use, amount used, room of use, etc.)
described in the Westat Survey (from 1987) is believed to remain strong when compared to present day
consumer use patterns even though some aspects of the use may have changed (electronics cleaners
were applied to VCRs in 1987, but now are applied to computer motherboards or DVD players).
However, ease of access to products on-line or in big box stores (like home improvement stores), readily
accessible how-to videos, and a consumer movement toward more do-it-yourself projects with products
containing the chemical of concern could impact the representativeness of the consumer use patterns
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described within the Westat Survey and may lead to an underestimate of overall consumer exposure.
There is a high confidence associated with the representativeness of the consumer use patterns described
within the Westat Survey and present-day consumer use patterns.
Other Uncertainties:
There are several other factors to which some level of uncertainty may apply. These include, but are not
limited to, product use/availability, model specific factors, building characteristics, and use of personal
protective equipment or natural/engineered controls.
As described in Section 2.4.2.1, the market profile was developed in 2017 based on information
available at that time. These do not take into consideration company-initiated formulation changes,
product discontinuation, or other business or market-based factors that occurred after the documents
were compiled. However, unless these factors were in process while the dossier and market profile were
being developed, it is unlikely any significant changes occurred since such changes often require
considerable time to research, develop, and implement I ¦ \ en with discontinuation of products, while
they may readily be removed from shelves, product already purchased or picked up to he sold online
shortly before discontinuation will take some time to work out of the system. There is a medium
confidence associated with the product use/availability of product containing the chemical of concern.
There are multiple model specific factors to u liicli a level of uncertainly may apply including user
groups (age groups), building characteristics, and inherent model parameters.
There are multiple building characteristics considered when modeling consumer exposure including, but
not limited to, room size, ventilation rate, and building size I or this evaluation, we relied on default
values within the models for these parameters. These default \ allies were primarily obtained from the
Exposure Factors Handbook (u S ). There is a medium to high confidence associated with
these parameters.
Room size varied for this evaluation based on room of use obtained from the Westat Survey (1987) data.
Room size relates lo the \ olume of llie room and is a sensitive parameter within the models. However,
the room size of a standard bedroom, living room, kitchen, utility room, one or two car garage, etc.
should be relati\ ely consistent across building types (small or large residential homes, apartments,
condominiums, or townhomes) Therefore, any uncertainty associated with room size is derived more
from the room of use selected, rather than the wide variety of sizes of a particular room of use. Since the
rooms of use selected for this evaluation are based on data collected by the Westat Survey, there is a
high confidence associated with room sizes used for this evaluation.
Ventilation rate is another sensitive parameter within the models. Similar to the room of use, however,
ventilation rates should be relatively consistent across building types where ventilation systems are
properly maintained and balanced. Centralized ventilation systems are designed to deliver ventilation
rates or air exchange rates which meet the American Society of Heating, Refrigeration, and Air
Conditioning Engineers Standard Recommendations which are established for rooms, house types,
commercial buildings, and others. Centralized ventilation systems may be larger for larger homes, but
the ventilation rates delivered to the specific room of use should be relatively consistent across building
types. Therefore, any uncertainty associated with ventilation rates is derived more from the proper
design, balancing, and maintenance of ventilation systems. Ventilation rates for a particular room of use
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could be impacted by use of fans or opening windows within the room of use, however, most
respondents to the Westat Survey indicated they did not have an exhaust fan on when using the products.
Most respondents kept the door to the room of use open but did not open doors or windows leading to
the outside when using the products. There is a medium to high confidence associated with the
ventilation rates used for this evaluation.
Building size is another sensitive parameter within the models, however, the sensitivity derives from
more mixing and dissipation outside of the room of use. There will be more variability in building size
across building types so there is a medium confidence associated with building size.
The use of personal protective equipment or natural/engineered controls by a consumer during product
use is uncertain. It is not expected that consumers will utilize personal protect i\ e equipment like full
face respirators, or engineering controls like hoods when using consumer products in a residence or
building to reduce inhalation risks. While it may be slightly more likely that, for certain products,
consumers may choose to wear gloves or eye protection, neither of these address inhalation exposure.
Use of gloves by a consumer could decrease dermal exposure, assuming the gloves are high quality and
chemical resistant. Latex gloves are readily available; however, such gloves tear easily, and may not be
resistant to breakdown by certain products used. Although the use of gloves could reduce dermal
exposure, if used improperly (for example fully immersing hands into a product) could allow for leakage
into the glove.
Confidence:
There is an overall medium confidence in all the results found lor the consumer scenarios identified in
Table 2-68 and evaluated in this evaluation. This confidence deri\ es from a review of the factors
discussed above as well as piv\ ions discussions about the strength of the models and data used,
sensitivity of the models, and approaches taken for this evaluation.
The models used for this e\ alnation are peer reviewed models. The equations are derived, justified and
substantiated by peer reviewed literature as described in the respective user guides and associated user
guide appendices. The default values utilized in the model (and retained for this evaluation) are a
combination of central tendency and high-end estimates from both peer reviewed literature and the
Exposure Factors Handbook ( A, 20.1 i) providing a representative spectrum of modeling results.
Even though some values have high end values (like building size or ventilation rates), it should be
recognized that these parameters are correlated, and that "higher" building sizes or higher ventilation
rates would he expected to result in more mixing and dissipation leading to a lower exposure.
The data used in lieu of default values within the model are a combination of central tendency, and high-
end values from the Westat Survey, which was rated as a high-quality study as part of the systematic
review process. The t\vel\ e use scenarios evaluated for this evaluation aligned well with specific
scenarios within the Westat Survey, pre-defined model scenarios, and other approaches taken. The
deterministic approach taken for consumer exposure in this evaluation involved varying three
parameters that were either highly sensitive or representative of consumer use patterns or both. The three
parameters varied also provided a broad spectrum of consumer use patterns covering low, moderate, and
high intensity uses and therefore are not limited to a high-end, worst-case type situation or an upper
bounding estimate. Other aspects of the deterministic approach taken (like a single product used once
per day) may result in an underestimate of actual consumer exposure.
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2.5 Other Exposure Considerations
2.5.1 Potentially Exposed or Susceptible Subpopulations
TSCA § 6 requires that a risk evaluation "determine whether a chemical substance presents an
unreasonable risk of injury to health or the environment, without consideration of cost or other non-risk
factors, including an unreasonable risk to a potentially exposed or susceptible subpopulation identified
as relevant to the risk evaluation by the Administrator, under the conditions of use." TSCA § 3(12)
states that "the term 'potentially exposed or susceptible subpopulation' means a group of individuals
within the general population identified by the Administrator who, due lo either greater susceptibility or
greater exposure, may be at greater risk than the general population of ad\ eise health effects from
exposure to a chemical substance or mixture, such as infants, children, pregnant women, workers, or the
elderly."
In developing the draft risk evaluation, EPA analyzed reasonably available inlbniialion lo ascertain
whether some human receptor groups may have greater exposure potential or susceptibility to NMP than
the general population. Because risk determinations w ere leased on potential reproductive and
developmental effects of NMP exposure that may occur at sensitive lifestages, they account for risks to
susceptible subpopulations, including pregnant women, children, adolescents, and men and women of
reproductive age. It was assumed that exposures which do not result in unreasonable risks for this
population would also be protective of other populations because other health effects are expected to
occur at high levels of NMP exposure.
EPA estimated exposures to children who may be located near the consumer user at the time of use and
determined that these exposures were below the le\ els of concern identified for adverse developmental
effects and would therefore be below the levels of concern for other hazard effects that may be
associated with higher NMP exposure levels.
2.5.2 Aggregate and Sentinel Kxposnres
As a part of risk evaluation, Section »5( h)(4)(I )(ii) of TSCA requires EPA to describe whether
aggregate or sentinel exposures were considered under the identified conditions of use and the basis for
their consideration. I-I\\ has defined aggregate exposure as "the combined exposure to an individual
from a single chemical substance across multiple routes and multiple pathways." (40 C.F.R. 702.33).
EPA defines sentinel exposure as "exposure to a single chemical substance that represents the plausible
upper bound relati\ e to all other exposures within a broad category of similar or related exposures." (40
C.F.R. 702 33) N\\ considered sentinel exposure in the form of high-end estimates for consumer and
occupational exposure scenarios which incorporate dermal and inhalation exposure, as these routes are
expected to present the highest exposure potential based on details provided for the manufacturing,
processing and use scenarios discussed in the previous section. The exposure calculation used to
estimate dermal exposure to liquid is conservative for high-end occupational and consumer scenarios
where it assumes full contact of both hands and no glove use.
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3 HAZARDS
3.1 Environmental Hazards
3.1.1 Approach and Methodology
EPA identified environmental hazard data for NMP through an extensive literature search as described
in detail in Section 1.5 and depicted in Figure 1-8. This process was completed in 2019 as part of this
RE with a portion of the search completed in 2017 as part of the NMP problem formulation.
EPA in the NMP Problem Formulation ( 2018c) did not conduct any further analyses on
pathways of exposure for terrestrial receptors in line with Section 2.5.3.1. The Problem Formulation did
not identify Environmental Hazards for either aquatic or terrestrial receptors. The analysis was based on
a qualitative assessment of the physical-chemical properties and fate of NMP in the en\ ironment and a
quantitative comparison of the hazards and exposures identified for aquatic organisms.
Subsequent to that analysis, an additional five "Key/Supporting" citations were identified by EPA after
review of the OECD HPV SIDS Document for NMP (C ) EPA obtained the full study
reports from the NMP Producer's Group (BASF and GAI ) As these studies raised concerns for
Environmental Hazards associated with NMP and aquatic receptors, a quantitative evaluation of hazards
to aquatic receptors is included as part of this Rl- l-P A conducted no further analyses of exposure and
hazards for terrestrial receptors and instead relied on the analyses conducted as part of the NMP Problem
Formulation.
3.1.2 Hazard Identification
EPA quantitatively evaluated impacts to aquatic organisms, including fish, aquatic invertebrates and
algae from acute and chronic NMP releases to surface water. The hazard characterization for all
identified environmental hazard endpoints are summarized in Table 3-1. The environmental hazard data
were re\ iewed for acute and chronic exposure duration related endpoints (e.g., mortality, growth,
immobility, reproduction) No ecotoxicity studies were identified for sediment-dwelling organisms.
3.1.2.1 Toxicity Data for Aquatic Organisms
EPA evaluated lour studies for NMP acute exposures for fish. The acute 96-hour LCso values reported
for fish range from 5< )<) mg/L. for the freshwater rainbow trout (Oncorhynchus mykiss) to 4,030 mg/L
for the freshwater orle U caci sens idus).
For NMP acute toxicity data were evaluated for aquatic invertebrates for four species including the
freshwater water flea {Daphnia magna), the saltwater grass shrimp (Palaemonetes vulgaris), the
saltwater mud crab (Neopanope texana sayi), and the freshwater scud (Gammarus sp.) (GAF. 1979).
The results of these studies are summarized in Table 3-1 with more detail provided in Appendix G. The
48-hr ECso for NMP and D. magna is reported as 4,897 mg/L. The 96-hr LC50 's for grass shrimp, mud
crab, and scud are reported as 1,107, 1,585 and 4,655 mg/L, respectively (GAF. 1979).
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For the fresh water green algae (Scenedesmus subspicatus), the 72-hr ECso values were 600 mg/L
(Biomass) and 673 mg/L (Growth rate) ( !9).
EPA evaluated one chronic toxicity study for NMP exposures for freshwater invertebrates (I). magna).
A 21-day study with I). magna reported reproductive effects for NMP with a No-Observed Effect
Concentration (NOEC) of 12.5 mg/L and a Lowest Observed Effect Concentration of 25 mg/L, resulting
in a calculated chronic toxicity value of 17.68 mg/L (geometric mean of NOEC and LOEC) (
2001).
Chronic aquatic toxicity data are not available for NMP for fish. EPA estimated a chronic fish toxicity
value based on an acute to chronic ratio (ACR) approach extrapolating from the acute fish toxicity data.
The acute 96-hour LCso value for rainbow trout of >500 mg/L was divided by I n resulting in an
estimated chronic fish toxicity value for NMP of >50 mg/L
EPA evaluated one chronic aquatic toxicity study for aquatic plants. The green algae {Scciicdesmus
subspicatus) was exposed to NMP for 72-hours. The NOI-C value for NMP was reported at 125 mg/L
and the LOEC at 250 mg/L. EPA calculated a chronic toxicity \ aluc of 177 mg/L (geometric mean of
NOEC and LOEC) (BASF AG. 1989V
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Table 3-1. Aquatic Toxicity Data for NMP
Duration
Test Taxa
Kiulpoint
Hazard value*
1 nits
i: fleet
Kiul point
Reference
Fish
yb-hour
LC50
>500-4,030
mg/L
Mortality
( )
(High). (
1986)
Acute
Aquatic
invertebrates
48/96 hour
EC50/LC50
1,107-4,897
mg/L
Immobilizatio
n/Mortalitv
( >)
Algae
72-hour
EC50
600 (Biomass)
673 (Growth rate)
mg/L
Growth
( 89)
Acute Concentration of
Concern (COC)
>100
niij L
Estimated by dividing lowest reported
acute value across test organisms (<500)
bv an Application Factor (AF) of 5
Fish
Chronic
Value
(ChV)
>50
mg/L
Estimated by el 1 \ tiling lowest reported
acute value for fish ( 5< )< 1) by an acute
to chronic ratio ol" 10.
Aquatic
NOEC
LOEC
12.5 (Reported)
25 (Reported)
my 1.
Reproduction
( 01)a
Chronic
invertebrates
Chronic
Value
17.7
I11L2 1.
1 Estimated by calculating the geometric
mean ol'the NOEC and LOEC.
Algae
NOEC
LOEC
125 (Reported)
250 (Reported)
niij L
Grow 1I1
(BASF AG. 1989)
Chronic
Value
177
niij 1.
Estimated by calculating the geometric
mean of the NOEC and LOEC
Chronic Concentration of
Concern (( ()( )
1 77
mg/L
Lowest calculated or reported chronic
value across taxa divided by an AF of
10.
*Values in the tables are presented as reported h\ ihe study authors: Bold = experimental data
aReservation of Rights: BASF has aurced in share this toxici l> study report ("Study Report") with US EPA, at its written
request, for EPA's use in implement nm a slalulor> requirement of the Toxic Substances Control Act ("TSCA "). Every other
use, exploitation, reproduction. distribution. publication or submission to any other party requires BASF's written permission,
except as otherwise pro\ ided In law The suhinission of this Study Report to a public docket maintained by the United States
Environmental Protection \ueuc> is not a wai\ or of BASF's ownership rights. No consent is granted for any other third-party
use of this Study Report lor au\ purpose, in au\ jurisdiction. Specifically, and by example, no consent is granted allowing the
use of this Study Report by a pri\ ale entity iu requesting any regulatory status, registration or other approval or benefit,
whether ii iierual loual. national, state or local, including but not limited to the Regulation Evaluation Authorization and
Restriction of Chemicals ("REACH") regulation administered by European Chemicals Agency ("ECHA"), an agency of the
European Union
3724 3.1.2.2 Concentrations of Concern Calculation
3725 Acute and chronic COCs were calculated for environmental toxicity of NMP using assessment factors.
3726 EPA applied an assessment factor (AF) according to EPA methods (U.S. EPA. b. 2012d). The
3727 application of AFs provides a lower bound effect level that would likely encompass more sensitive
3728 species not specifically represented by the available experimental data. AFs can also account for
3729 differences in inter- and intra-species variability, as well as laboratory-to-field variability. These AFs are
3730 dependent on the availability of datasets that can be used to characterize relative sensitivities across
3731 multiple species within a given taxa or species group. However, they are often standardized in risk
3732 assessments conducted under TSCA, since the data available for most industrial chemicals are limited.
3733 For fish and aquatic invertebrates (e.g., daphnia) the acute toxicity values are divided by an AF of 5. For
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chronic COCs, an AF of 10 is used. The COC for the aquatic plant endpoint is determined based on the
lowest value in the dataset and application of an AF of 10 (U.S. EPA. 2013b. 2012d).
After applying AFs, EPA converts COC units from mg/L to |ig/L (or ppb) in order to more easily
compare COCs to surface water concentrations during risk characterization.
Acute COC
To derive an acute COC for NMP, EPA used the lowest reported acute toxicity value across taxa (>500
mg/L) and divided by the AF of 10 and multiplied by 1,000 to convert from mg/L to |ig/L, or ppb.
The acute COC = (>500 mg/L) / AF of 5 = 100 mg/L x 1,000 = loo.ooi) jliu I. or ppb.
• The acute COC for NMP is 100,000 ppb.
Chronic COC
The chronic COC for NMP was derived by EPA by di\ idinu the ac|Lialic invertebrate 21-day chronic
toxicity value of 17.7 mg/L (1,768 |ig/L) by an assessment factor of I"
The acute COC = (17.7 mg/L) / AF of 10 I 77mgl.\ I.<)<)<) 1,77i) iigU or ppb.
• The chronic COC for NMP is 1,77<) pph
3.1.2.3 Toxicity lo Soil/Sodiniont and Terrestrial Organisms
EPA did not further c\ alualc in this Rl- exposure pathways (and hazards) associated with NMP in
sediments and soils based on analyses completed as part of the NMP Problem Formulation (
2018c).
3.1.3 Weight ol'Scientific Kvidcncc
During the data integration stage of EIWs systematic review for risk evaluation, EPA analyzed,
synthesized, and integrated the data/information. This involved weighing scientific evidence for quality
and rele\ ance. usi nu a Weight of Scientific Evidence (WOE) approach ( 016). In the June
2018 Problem I 'oi nuilation for N-Methylpyrrolidone (NMP) ( ), seven studies were
used to conduct a basic screening-level characterization the environmental hazards of NMP. At the time
of the problem formulation, none of these studies identified during the literature search or ECHA
summaries had been evaluated according to the systematic review criteria. Since the NMP Problem
Formulation ( .., 8c) these studies have been evaluated according to the systematic review
criteria in The Application of Systematic Review in TSCA Risk Evaluations (U.S. EPA. 2018a).
While EPA determined that there were enough environmental hazard data to characterize environmental
hazards of NMP, there are uncertainties. First, assessment factors (AFs) were used to calculate the acute
and chronic concentrations of concern for NMP. AFs account for differences in inter- and intra-species
variability, as well as laboratory-to-field variability and are routinely used within TSCA for assessing
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the hazard of new industrial chemicals (with very limited environmental test data). Some uncertainty
may be associated with the use of the specific AFs used in the hazard assessment.
Second, more acute duration data were available in the literature than chronic duration data. Therefore,
EPA is less certain of chronic hazard values than the acute hazard values. The most sensitive taxonomic
group from the acute duration data, aquatic invertebrates, has chronic duration data available in the
literature. Because the chronic fish data were not available, the chronic fish endpoint was addressed
using the acute to chronic ratio (AF=10). The fish chronic toxicity value was estimated to be >50 mg/L.
3.1.4 Summary of Environmental Hazard
The acute 96-hour LCso values for fish range from >500 mg/L to 4,030 mg/L The acute ECso/LCso for
aquatic invertebrates range from 1,107 mg/L to 4,897 mg/L. For fresh water green algae, the 72-hr
ECso values were 600 mg/L (Biomass) and 673 mg/l. ((irouth rate). EPA calculated the acute COC to
be 100,000 |ig/L (10 mg/L).
For the chronic fish endpoint, an acute to chronic ratio (ACR) approach was used to extrapolate a
chronic toxicity value for NMP for fish based on the reported acute values. EPA calculated a chronic
fish toxicity value for NMP of >50 mg/L using an ACR of 10 and the lowest reported acute toxicity
value of >500 mg/L. For the aquatic invertebrate endpoint, a 21 -day chronic toxicity value of 17.68
mg/L was calculated for NMP based on reproduction (geometric mean of the reported NOEC of 12.5
mg/L and LOEC of 25 mg/L). For the chronic aquatic plant endpoint, a 72-hour chronic toxicity value
of 177 mg/L was calculated for NMP based on growth inhibition (geometric mean of the reported
NOEC of 125 mg/L and the LOF.C of 250 mg/L) I-1\\ calculated the chronic COC 1,770 jig/L (1.77
mg/L).
The aquatic toxicity studies used to characterize the effects of acute and chronic NMP exposure to
aquatic invertebrates are summarized in Table 3 1.
3.2 Human Health Hazards
3.2.1 Approach and Methodology
EPA identified hazard data for NMP through an extensive literature search as described in EPA's
Strategy jor Conducting Literature Searches for NMP: Supplemental Document to the TSCA Scope
Document (U.S. ET 117d). Only the identified "on-topic" references (as explained in the N-
Methylpyrrolidone a \SRS 872-50-4) Bibliography: Supplemental File for the TSCA Scope Document
(U.S. EPA. 2017b)) obtained from the human health hazard literature search were considered as relevant
data/information sources for consideration in this draft risk evaluation of NMP. EPA's inclusion criteria
were used to screen the initial literature search results (n = 1,397); 1,361 references were excluded based
on PECO. In addition, three key/supporting studies were identified outside of this process and included
in the current evaluation. The remaining hazard studies (n=36) were then evaluated using the data
quality evaluation criteria for human health hazard studies as outlined in The Application of Systematic
Review in TSCA Risk Evaluations (U, S. EPA. 2018a). The hazard data determined to be acceptable
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based on this data quality review were extracted and integrated. This systematic review process is
summarized in Figure 3-1.
The human health hazard of NMP has been examined in several publications (EC. 2016; Danish
Ministry of the Environment 2015; U.S. EPA. 2015; NICNAS. 2013; OECD. 2009b. I S < I; \ :006b;
WHO. 2.001). EPA relied heavily on the hazard information presented in these documents to inform the
human health hazard identification and the dose-response analysis. EPA also evaluated studies that were
published since these reviews during the analysis phase of the risk evaluation, as identified in the
literature search conducted by the Agency for NMP (NMP (CASRN 872-50-4) Bibliography:
Supplemental File for the TSCA Scope Document (s ' i 'c).
Brief summaries for each hazard endpoint are presented in Section 3.2.3. Detailed information about
study quality review for study selection is provided in Section 1.5.1. Developmental and reproductive
toxicity endpoints were evaluated for consistency, sensili\ ily and relevance (Section 3 2 3). Based on
the conclusions of previous assessments and a review of a\ ailable studies, EPA narrowed the focus of
the NMP hazard characterization to specific reproducth e and developmental toxicity endpoints, reduced
fertility, including fetal resorptions (mortality) and growth retardation. EPA conducted a dose-response
assessment for these endpoints (Section 3.2.5), using benchmark dose analysis and PBPK model
estimates of internal doses (Section 3.2.5.6) to select points of departure (POD) for use in the risk
evaluation (Section 4.2).
EPA considered new (on-topic) studies with information on acute and non-cancer endpoints for hazard
identification and dose-response analysis if the study recei \ eel an overall data quality rating of high,
medium, or low as described in the Application of Systematic Re\ iew in TSCA Risk Evaluations (U.S.
E 18a). EPA has not developed data quality criteria for all types of relevant information (e.g.,
toxicokinetic data); however, this i nlbrmation was used to support the risk evaluation. Information that
was rated unacceptable was not included in the risk evaluation. The human health hazard data used to
characterize the effects of acute and chronic NMP exposure to humans are summarized in Table
3-12.Table 3-10. Additional information on the human health hazard endpoints considered during hazard
identification, are pro\ ided in \ppcnclix 11 The comprehensive results of the study evaluations can be
found in — ' : ;w: Supplemental File for the TSCA Risk Evaluation
L jL-HQ-C 19 '
The human health hazard information wab integrated using a strategy that includes consideration of the
weight of the scientific evidence for each hazard endpoint to select the data used for dose-response
assessment. The weight of scientific evidence analysis included integrating information from
toxicokinetics and toxicodvnamics in relation to the key hazard endpoints which include reproductive
and developmental toxicity Dose-response analyses that were performed using benchmark dose
modeling in the pre\ ious assessment of NMP use in paint and coating removal ( 2.015) were
incorporated where appropriate (see Section 3.2.5). Additional benchmark dose modeling was conducted
for the current risk evaluation to include data on reproductive toxicity that was previously unavailable to
EPA.
Studies that met the evaluation criteria and were rated low, medium, or high were considered for hazard
identification and dose-response analysis as described in the Application of Systematic Review in TSCA
Risk Evaluations ( 018a). EPA has not developed data quality criteria for all types of hazard
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information such as toxicokinetic data; however, this information is used to support the NMP risk
evaluation.
Studies considered PECO relevant that scored acceptable in the systematic review data quality
evaluation and contained adequate dose-response information were considered for derivation of points
of departure (PODs). EPA defines a POD as the dose-response point that marks the beginning of a low-
dose extrapolation. This point can be the lower bound on the extrapolated dose for an estimated
incidence, a change in response level from a dose-response model (e.g., benchmark dose or BMD), a
NOAEL value, a lowest-observed-adverse-effect level (LOAEL) for an observed incidence, or a change
in the level (i.e., severity) of a given response. PODs were adjusted as appropriate to conform to the
specific exposure scenarios evaluated.
Risk Characterization
Data
Extraction
Extract
key, supporting
and new studies
from
Human Health Hazard Assessment
Data Evaluation
After full-text screening,
apply pre-determined data
quality evaluation criteria
to assess confidence in
key and supporting studies
identified from previous
assessments as well as
new studies not
considered in previous
assessments
• Uncertainty and variability
• Data quality
• PESS
• Alternative interpretations
Ris k Characte rizatio n
Analysis
Determine the qualitative
and/or quantitative human
health risks and include, as
appropriate, a discission of
Data Integration
Integrate hazard information by considering quality (ie.,
strengths, limitations), consistency, relevance, coherence at
biological plausibility
Hazard ID
Confirm potential
hazards identified
during
scoping/prob lem
formulation and
identify new hazards
from the literature (if
applicable)
D os e -Re sponse
Analysis
Benchmark dose
modeling for
endpoints with
adequate data;
Selection of PODs
Systematic
Review
Stage
Output of
Systematic
Review
Stage
Study Quality
Summary Table
(High, Medium,
Low)
(Section 3.2.3)
Data Summaries
for Adverse
(Appendix H.1)
WOE Narrative
by Adverse
Endpoint
(Section 3.2.4)
Summary of
Results and
POD selection
(Section 3.2.5)
Risk Estimates
and
Uncertainties
(Sections 4.1
through 4.3)
Figure 3-1. Summary of NMP Systematic Review
3.2.2 Toxicokinetics
NMP is readily absorbed by all routes with widespread distribution via the systemic circulation and
extensive first pass metabolism to polar compounds that are excreted primarily in urine (Akesson et al..
2004; Ligocka et al.. 2003; Akesson and Paulsson. 1997). The major metabolites of NMP in humans are
5-hydroxy-N-methyl-2-pyrrolidone (5-HNMP) and 2-hydroxy-N-methylsuccinimide (2-HMSI); minor
metabolites include N-methyl-succinimide (MSI). Over 80% of the administered dose is excreted within
72 hours (Akesson et al.. 2004; Akesson and Paulsson. 1997).
Dermal contact with NMP liquids generally presents the greatest potential for human exposure;
however, vapor-through skin uptake has also been demonstrated in humans (Akesson et al.. 2004;
Jonsson and Akesson. 2003). Bader et al. (2008) exposed human volunteers to an NMP air concentration
of 80 mg/m3 for 8 hours and estimated peak concentrations following dermal-only exposure to be in the
range of 36 to 42% of the results obtained after whole-body exposure based on NMP equivalents in
urine (See Section 3.2.5.5).
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3.2.3 Hazard Identification
Previous assessments ( ; ; ;
2013; OECD. 2009b. * 1 \ 1" \ .2006b; WHO. 2001) have identified reproductive and developmental
toxicity as the most sensitive effects of NMP. EPA therefore focused this risk evaluation on reproductive
and developmental effects. This section summarizes evidence for reproductive and developmental
hazards as well as a broader range of potential non-cancer and cancer health hazards.
A comprehensive set of summary tables which includes all endpoints considered for this assessment
may be found in Appendix H. EPA reviewed the available data and key and supporting studies were
evaluated for consistency and relevance to humans, according to the Application of Systematic Review in
TSCA Risk Evaluations ( i). The results of the data quality e\ aluation for the non-cancer
studies (key and supporting studies and new studies) are described below in Section 3.2.3.1 and included
in the data quality evaluation tables in the Systematic Review Supplemental File: / kna Quality
Evaluation of Human Health Hazard Studies. Docket El'. I-/IQ-OPPT-2019-0236 ( PA. 2019m).
3.2.3.1 Non-Cancer Hazards
Toxicity following Acute Exposure
The acute toxicity of NMP is low based on results from studies conducted via oral, dermal, inhalation,
intraperitoneal and intravenous exposure in rats and mice (RIVM. ; OECD. 2007b; WHO. 2001).
Oral LD50 values ranged from 3605 to 7725 mu ku-hw. dermal LD;.. \ alues ranged from 5000 to 7000
mg/kg-bw and the 4 hr LC50 was > 5100 mg/111' ( ). Sublethal effects observed in response to
single high doses include body weight gain in rats exposed to 5 1 mg/L of a vapor/aerosol mixture, and
ataxia and diuresis in rats exposed orally to 1/8 of 1 lie 1.1)=.. U.,. ).
Irritation and Sensitization
NMP is a skin, eye and respiratory irritant (RIVM. 2013; WHO. 2001). For example, a rabbit 28-day
dermal exposure study with rabbits exposed to 413, 826, or 1653 mg/kg/day once a day, five days a
week for four weeks resulted in local skin irritation at all doses tested (OECD. 2007b; \U U % .001).
Rabbits receiving a single application of 0 I ml NMP to one eye experienced corneal opacity, iritis, and
conjunctivitis. Effects were reversible within 14 days (OECD. 2007). Nasal irritation (crust formation on
nasal edges) was obser\ ed i 11 rats exposed to 1, or 3 mg/L for 6 hours a day five days a week for three
months. The inhalation study identified a NOAEC of 0.5mg/L (BASF AG, 1994, as cited by OECD.
2007).
Human volunteer chamber studies revealed some discomfort during exposure but are otherwise
suggestive of humans being less sensitive to NMP irritation than rodents (RIVM. 2013). Workers
exposed to NMP dermall\ experienced skin irritation (Leira 1992 as cited by (OECD. 2007b)). No
respiratory irritation u as reported in workers and volunteers exposed via inhalation to up to 50mg/m3
for 8 hours ((Akessom < jnsson. 1997); NMP Producers Group 2005 as cited by (OE< 07b).
NMP is not corrosive. Although, available results suggest NMP is not a sensitizer ( ) data
are too limited to draw conclusions on sensitization.
Neurotoxicity
A small number of studies noted effects related to neurotoxicity. A RIVM report highlights a 90-day
oral repeat dose study in rats with a neurotoxicity screening panel that identified NOAELs of 169 and
217 mg/kg-bw/day for males and females, respectively, based on decreased body weight in both males
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and females and reversible neurological effects (including increased foot splay and low arousal) in males
only (RIVM. 2013; Mattev et al. 1999V
In a rat study, whole body exposure to 0.1, 0.5, and 1.0 mg/L (25, 125, or 250 ppm, aerosol) 6 hours/day
five times a week for four weeks was associated with lethargy and irregular respiration at all
concentrations. These signs were reversible within 30-45 minutes following exposure at the two lower
concentrations. Rats in the highest dose group had excessive mortality. Lethargy and irregular
respiration were not reversed in most surviving animals in the high dose group 18 hours after exposure
had ceased (Lee et al.. 1987). The actual exposure concentrations in this study cannot be determined due
to aerosol formation and condensation.
In a gestational exposure study by Lee et al. (1987) rats were exposed to an WIP aerosol concentration
of 100 and 360 mg/m3 (analytical) for six hours/day from GD 6 through 15 Sporadic lethargy and
irregular respiration were observed in treated dams at both exposure levels during the first three days of
exposure. These effects were not seen during the remainder of the exposure period or during the 10-day
recovery period.
Developmental neurotoxicity endpoints have also been e\ aluated. Hass et al. (1994) investigated the
effects of NMP on postnatal development and behavior in rats exposed during gestation. Dams were
exposed by whole-body inhalation to measured le\ els of 151 ppm ((•>12 mg/m3) for six hrs/day from GD
7 to 20 and offspring were evaluated for a range of growth, development, and neurobehavioral endpoints
from PND1 through 7 months of age. Performance was impaired in certain more complex tasks (i.e.,
reversal procedure in Morris water maze and operant delayed spatial alternation). The impaired
performance may be associated with decreased body weight at weaning. As the authors noted, the effect
appeared most pronounced in offspri ng u i th the lowest body weights in the litter at weaning. Since only
one dose was used, a M).\lvL could not he established. This study was excluded by the systematic
review process and did not go through data quality evaluation because it only used a single dose. It is
discussed here because it was cited as a supporting study in a previous EPA assessment (U.S. EPA.
2015). and it provides information about neurode\ elopniental endpoints that have not been evaluated in
any other studies.
Liver Toxicity
A chronic oral exposure study reported effects on the liver following oral exposure to NMP in rats and
mice. Chronic oral exposure in rats was associated with centrilobular fatty change in the liver in males
but not in females "I"tiis study identified a LOAEL of 678 mg/kg/day and a NOAEL of 207 mg/kg for
liver toxicity in male rats (v tattey et. al.. 2001). In mice, significantly increased liver weights as well as
cellular alterations in the li \ er were reported in both male and female mice following oral exposure. The
authors reported a l.OAl -1. of 173 mg/kg/day and NOAEL of 89 mg/kg/day for liver toxicity in male
mice (Mattey et al..¦ ). A sub-chronic 90-day oral exposure study in rats and mice at higher doses
found no effect on the liver (ivlallev et al.. 1999) while a four-week oral exposure study found increased
incidence of centrilobular hepatocellular hypertrophy in addition to increase serum total protein and
albumin in female rats exposed to 2268 mg/kg/day (Matek et al.. 1997).
Kidney Toxicity
Chronic progressive nephropathy was reported in male but not female rats following chronic oral
exposure to 678 mg/kg-bw/day (Mallev et al.. 2001). No kidney toxicity was observed in male or female
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mice in this study (Mallev et at.. 2001). The study identified a NOAEL of 207 mg/kg/day based on
kidney toxicity in male rats. Another study evaluated renal endpoints following four weeks of oral
exposure in mice. Dark yellow urine was observed in all animals at 2970 and 4060 mg/kg-bw/day.
Cloudy swelling of the distal renal tubule was observed in 3/5 females at 4060 mg/kg-bw/day. This
study identified a NOAEL for renal effects of 920 mg/kg-bw/day in females and 720 in males (BASF.
1994). A separate oral exposure study in which male rats received 500 mg/kg/day five days a week for
five weeks reported decreased creatinine. The NOAEL for decreased creatinine in male rats this study
was 250 mg/kg/day (Gopinathan et ai. 2013). This study also reported observations of mottled kidneys
in treated rats at all doses, but a lack of incidence data for this endpoint in each dose group prevents
identification of a NOAEL or LOAEL for renal effects.
Immune Toxicity
A whole-body inhalation study in rats, which likely included dermal and oral npuikc through grooming,
identified bone marrow hypoplasia, necrosis of lymphoid tissue in the thymus, spleen and lymph nodes,
as well as mortality at the highest dose (RIVM. 2.013). The NOAEC for immune effects and for other
systemic effects in this study was 500 mg/m3 (RJVMJ"1 °: '"""TP. 200711). In a foilr-u eek oral
exposure study, thymic atrophy was observed in female rats exposed to 2268 mg/kg-bw/day. The
NOAEL for thymus effects in this study was 1548 mg/kg/day ( ;k et. at.. 1997).
Developmental Toxicity
There is robust evidence of developmental toxicity in animals exposed to \\ll\ Developmental
inhalation, oral and dermal exposures to NMP have been linked to a range of developmental effects,
including decreased fetal and pup weights and increased fetal and pup mortality (Sitarek et at.. 2012;
NMP Producers Group. 1999a. at.., 1994). skeletal malformations, and incomplete skeletal
ossification (Saittenfail \ ; ¦ iPomt. 1990; Becci et at. ). Most of the available
developmental toxicity studies lor NMP were performed in rats. OECD and RIVM assessments also
describe rabbit developmental studies that reported developmental toxicity, including increased
resorptions and fetal malformations following gestational exposure to NMP in rabbits (RIVM. 2013;
OECD. 2007b).
Effects on postnatal neurological behavior were reported following whole-body inhalation exposure to
151 ppm (612 mg/m3) NMP during gestation (tiass et at.. 1994). However, because behavioral effects
were only e\ aluated at this single exposure level, no NOAEL has been identified for developmental
neurotoxicity and dose-response for this endpoint cannot be characterized.
Evidence of de\ elopmental toxicity and dose-response information from studies identified as acceptable
in the systematic re\ iew process is summarized in Table 3-2 and discussed in depth in Sections 3.2.4
and 3.2.5.
Reproductive Toxicity
Reproductive toxicity endpoints that have been observed following repeated exposure to NMP include
reduced male fertility and female fecundity and testicular histopathology. Evidence of reproductive
toxicity is inconsistent across studies. For example, three oral exposure studies in rats, including a
paternal exposure study, a maternal exposure study, and a two-generation study in both sexes (Sitarek et
at.. 2012; Sitarek and Stetkiewicz. 2008; Exxon. 1991) report reduced male and/or female fertility in
response to NMP. Three other two-generation studies in rats failed to identify any effect on fertility.
Two of these studies are two-generation dietary exposure studies in rats (NMP Producers Group. 1999a.
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b) with dose levels and study designs similar to the Exxon (1991) study. EPA does not have complete
access to the data from these studies and is therefore unable to assess data quality. The third study is a
two-generation whole-body inhalation exposure study (Solomon etal. 1995) that deviates substantially
from EPA and OECD guidelines. In addition, several oral exposure studies have reported effects on
testicular histopathology in male rats (Sitarek and Stetkiewicz. 2008; Mallev et at.. 2001; Malek et at..
1997). while several others find no effect (Mallev et at.. 1999; Becet et at.. 19* , I hvPont. 1982).
Evidence of reproductive toxicity is summarized in
Table 3-3 and discussed in depth in Sections 3.2.4 and 3.2.5. Reproductive toxicity findings are
challenging to interpret due to the wide-ranging effect levels and the lack of consistency in findings
across studies. While developmental effects are more consistently reported across studies, reductions in
fertility have been reported at lower doses than developmental effects following repeated exposures.
Table 3-2. Acceptable Studies Evaluated for Developmental Effects
Data
Source
Study Description
KITects reported: POD
Data
Quality
Rating
Oral Exposure Studies
(Sitarek
and
Stetkiewicz
,2008)
Oral gavage exposure (0, 100,
300, 1000 mg/kg-bw/day) 5
days/week for 10 weeks in male
rats before mating and for one
week during mating
Reduced viability of offspring in first
lour days of life following paternal
exposure to 300 mg/kg/day; NOAEL =
loo mg/kg-bw/day
High
(Sitarek et
at.. 2012)
Oral gavage exposure (0, 15<).
450, 1000 mg, kg-bw day) for 5
days/week for 2 weeks in female
rats prior to mating, during
mating, gestation and lactation
Number of li\e pups was reduced at
lOOOmg/kg-bw/day; Pup survival
decreased in all exposure groups;
LOAEL for pup survival =150 mg/kg-
bw/day
High
(Saittenftif
t
)
Oral ga\ age exposure (0, 125,
25<). 5<)<). 75<) mg kg-bw/day)
through gestational days (GD) 6-
2<) i n rats
Increased resorptions/ post-implantation
losses and increased skeletal
malformations; NOAEL for
developmental effects =125 mg/kg-
bw/day; NOAEL for maternal toxicity =
250 mg/kg-bw/day
High
(Exxon.
)
Two-generation oral dietary
exposure (50, 160, 500 mg/kg-
ln\ day) in male and female rats
exposed prior to mating,
throughout gestation and
lactation
Reduced pup survival and growth at 500
mg/kg-bw/day; NOAEL for
developmental effects =160 mg/kg-
bw/day
High
(Exxon.
1992)
Oral gavage exposure (40, 125,
400 mg/kg-bw/day) through GD
6-15 in rats
Reduced fetal body weights, reduced
ossification sites in proximal phalanges
of the hindpaw, and reduced maternal
body weight gain at 400 mg/kg-bw/day;
NOAEL for maternal and developmental
effects =125 mg/kg-bw/day
High
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Source
Study Description
KITects reported: POD
Data
Quality
Kill in«
Inhalation Exposure Studies
(Saillenfait
et ai.
2003)
Inhalation exposure (0, 122, 243,
487 mg/m3) for 6 hours/day on
GD 6-20 in rats
Reduced maternal weight gain and food
consumption at 243 mg/m3; Reduced
fetal weight at 487 mg/m3 exposure;
NOAEL for maternal effects= 122
mg/m3; NOAEL for developmental
effects= 243 nm'm3
High
(Solomon
et al.
1995;
DuPonl
1990)
Inhalation exposure (0, 42, 206,
472 mg/m3) for 6 hours/day
throughout mating period (100
exposure days) in male rats, and
throughout gestation and
weaning, except GD 20 - PND 4
(143 exposure days) in females
Decreased fetal body weights and
decreased offspring weights, decreased
maternal response to auditory stimulus at
the highest dose; NOAEL for maternal
and de\ elopmental effects = 206 mg m'
High
(Lee et al..
1987)
Inhalation exposure (100 or 360
mg/m3) for 6 hours/day on
gestational days 6-15 in mis
No effects reported on uterine or litter
parameters, lelal weight or length, or
incidence of gross, soft tissue, or skeletal
anomalies; NOAEL for maternal and
developmental effects = 360 mg/m3
Medium
Dermal Exposure Studies
CBecci et
al. 1982}
Dermal exposure (75. 237, 750
mg kg-ln\ day) on gestational
days (¦>-15 in mis
Decreased number of live fetuses per
dam, increased percentage of resorption
sites and skeletal abnormalities as well as
maternal toxicity indicated by reduced
body weight gain at the highest dose;
NOAEL = 237 mg/kg-bw/day
Medium
Table 3-3. Acceptable Studies Kvaluated for
Reproductive Effects
Data
Source
Study Description
Kffects reported: POD
Data
Quality
Rating
Oral Exposure Studies
(Sitarek
and
Stetkiewic
z. 2008)
Oral gavage exposure in male
rals(D. 1 on. 300, lOOOmg/kg-
bw/day) 5 days/week for 10
weeks prior to mating and for
one week during mating
Male infertility, damage to seminiferous
epithelium and significant reduction in
thyroid weight at 1000 mg/kg-bw/day;
NOAEL for male reproductive effects =
300 mg/kg-bw/day
High
(Sitarek et
al. )
Oral gavage exposure (0, 150,
450, 1000 mg/kg-bw/day) for 5
days/week for 2 weeks in
female rats prior to mating,
during mating, gestation and
lactation
Significant reduction in female fertility
index at 450 or 1000 mg/kg-bw/day;
NOAEL for female fertility =150 mg/kg-
bw/day
High
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Source
St lid v Description
Effects reported: POD
D:it:i
Qiiiilitv
Knt in«
(Exxon.
1991)
Two-generation oral dietary
exposure (50, 160, 500 mg/kg-
bw/day) in male and female
Sprague-Dawley rats exposed
prior to mating, throughout
gestation and lactation
Reduced male fertility and female
fecundity in second generation rats
(exposed throughout development and
prior to mating) at all doses; LOAEL= 50
mg/kg-bw/day; NOAEL not identified
High
(Becci et
ai. 1983s)
Oral dietary exposure (0, 24,
75, 246 mg/kg-bw/day in males;
0, 24, 76, 246 mg/kg-bw/day in
females) for 13 weeks in male
and female beagle dogs
No effects on reproducti\ e organ weights;
NOAEL for repioducli\ e effects ~ 246
mg/kg-bw/day
High
(Malek et
ai. 1997s)
Oral dietary exposure (0, 2000,
6000, 18000 or 30,000 ppm; 0,
149, 429, 1234, 2019 mg/kg-
bw/day) for four weeks in male
rats
Decreased body weight and altered testes
and li\ cr weights observed at 1234 mg kg-
bw/day and above. Degeneration/atrophy
of testicular seminiferous tubules were
observed 1/5 males at 1234 mg/kg-bw/day
and in 5/5 at 2019 mg/kg-bw/day; NOAEL
lor reproductive effects = 429 mg/kg-
bw'dav
High
(Mallev et
ai. 1999)
Oral dietary exposure (0, 3000.
7500 or 18,000 ppm) for 90
days in male rats (<>. 433.
1057 mg/kg-bw day) and
female rats (<~>. 217. 5(->5. 1344
mg/kg-bw day), oral dietary
exposure (0, l19. 193 1 mu ku-
h\\ day)
No effect on reproductive organ weights.
NOAEL in rats = 1057 mg/kg-bw/day;
NOAEL in mice = 1931 mg/kg-bw/day
High
(Mallev et
ai. 200n
Chronic dietary oral exposure in
rats (0, 1600, 5000 or 15,000
ppm) for two years (0, 66.4,
2<)7. 078 mg/kg-bw/day in male
rats), (i). 87 8, 283, 939 mg/kg-
bw day in female rats) and
dietary exposure (0, 600, 1200
or 7200 ppm) for 18 months in
mice (0, 89, 173, 1089 mg/kg-
bw/day in male mice) and (0,
115, 221, 1399 mg/kg-bw/day
in female mice)
In male rats only, bilateral
degeneration/atrophy of seminiferous
tubules in the testes, and bilateral
oligospermia/germ cell debris in the
epididymis at the highest dose; NOAEL for
male reproductive effects = 207 mg/kg-
bw/day
High
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Data
Source
Studv Description
KITects reported: POD
Data
Quality
Knt in«
(
1994)
Oral dietary exposure (0, 500,
2500, 7500 or 10,000 ppm; 130,
720, 2130, 2670 mg/kg-bw/day)
for four weeks in male mice
No exposure related reproductive organ
effects reported; NOAEL for reproductive
effects in mice = 2670 mg/kg-bw/day
High
Inhalation
Exposure Studies
(Solomon
et aL,
1995;
DuPohL
1990)
Two generation whole body
inhalation exposure (0, 42, 206,
472 mg/m3) for 6 hours/day, 7
days/week throughout mating
period, gestation, and weaning
in male and female rats
No significant change in indices of
reproductive performance (fertility and
fecundity); NOAEL for reproductive
effects = 472 mg m'
High
(DuPoml
1982)
Chronic whole-body inhalation
exposure (0, 41, 405 mg/m3) 6
hours/day, 5 days/week for two
years in male and female rats
Mammary gland hyperplasia; No ad\ erse
effects reported based on histopathology of
the epididymis and prostate. NOAEL for
mammary gland effects =10 ppm (41
mg/m3); NO.\l-!l. Ibr male reproductive
effects = ion ppm (4<)5 mg/m3))
Medium
3.2.3.2 Genotoxicity and Cancer Hazards
3.2.3.2.1 Genotoxicity and Other Mechanistic Data
EPA has reviewed summaries of the unpublished genotoxicity studies identified below and has
contacted the data owners to obtain full studies. Although EPA did not evaluate the genotoxicity and
mechanistic studies using updated data quality criteria presented in Application of Systematic Review in
TSCA Risk Evaluations ( ). all studies are considered acceptable (e.g., conduct of the
studies, use and proper response of positive controls) as presented at the international OECD meeting
(SIAM 24) and publication in the Screening Information Assessment Report and Dossier (
2007h) One study considered to be invalid within OECD (2007b) is also described below.
In Vivo (ienotoxicity Studies
NMP has been evaluated for potential genotoxicity in several in vivo studies, summarized in Table 3-4.
NMP was examined for its clastogenic/genotoxic potential in vivo in the Chinese hamster cytogenic
assay and administered once daily by gavage in doses of 1,900 and 3,800 mg/kg bw/day. NMP treatment
led to signs of systemic toxicity but did not result in increased numbers of mitotic cells containing
structural chromosomal alterations or numerical chromosomal aberrations. An earlier screening study
also showed no clastouenic potential of NMP in vivo after whole body inhalation of 800 ppm (measured
value of 1,750 mg/m') for 6 hrs/day, 5 days/week for 6 weeks (BASF AG, 1976d) as cited in OECD
(2007b).
In a mouse bone marrow micronucleus test, NMP was dissolved in distilled water and administered to
NMRI mice once daily by gavage at 950, 1,900 and 3,800 mg/kg bw/day. NMP treatment led to clinical
signs of toxicity, including irregular respiration, abdominal position and poor general state. NMP did not
induce micronuclei in the polychromatic erythrocytes of mice treated up to a dose showing clinical signs
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of toxicity and bone marrow toxicity. No indication of a spindle poisoning effect was detected (BASF
AG, 1989c) as cited in OECD (2007b) and Engelhardt and Fleig ( 5).
NMP did not show mutagenic activity in germ cells in a dominant lethal test in male NMRI mice after
intraperitoneal treatment with a single dose of 393 mg/kg bw/day (380 |il/kg bw; BASF AG, 1976a;
Roehrborn and Vogel, 1967) as cited in OECD (2007b).
Table 3-4. Summary of In Vivo Genotoxicity Studies
Study Type
Dose level/
Concentration
Result
Remark
Reference
Cytogenetic assay,
Chinese hamster
1900, 3800 mg/kg
bw/day
oral (gavage), single
application
negative
Signs of
systemic
toxicity
Engelhardt and
Fleig, 1993
Cytogenetic assay,
Chinese hamster
3,244 mg/m3
inhalation (whole
body), 6 h(day,
5x/week, 6 weeks (28
exposures),
negali\ e
Whole body
exposure
liASI AG,
N7(hI
Micronucleus
assay,
Mouse (NMRI)
0, 950, 1900, 3800
mg/kg bw/day
oral (gavage), single
application
Negative, no
indication of a
spindle
poisoning
effect
Signs of
systemic and
bone marrow
toxicity
BASF AG,
1989c;
Engelhardt and
Fleig, 1993
Dominant lethal
assay,
Mouse (NMRI)
i"i. 393 mg kg
single i p .
negati\ e
No mutagenic
activity in
germ cells
BASF AG,
1976a;
Roehrborn and
Vogel, 1967
Source: OECD (200" ). T;ihle p >2. ;ill references ;ire ciled in OECD (2007b)
In Vitro (ienoto.xicity Studies
In vitro studies e\ aluating potential genotoxicity of NMP are summarized in Table 3-5. NMP was tested
for mutagenicity in the Ames test on bacteria both with and without metabolic activation. The
Salmonella lyphimurium strains TA 9S. TA 100, TA 1535 and TA 1537 were exposed to the test
substance at concentrations ranging from 3.15 to 30,000 nl/plate. NMP was not mutagenic in the Ames
test under the experimental conditions used (BASF AG, 1978a) as cited in OECD (2007b). Wells (1988)
evaluated NMP in an Ames assay using several S. typhimurium strains both with and without metabolic
activation. In the assay without activation, increased revertants were observed for TA 102 and TA 104
but the increases were not greater than two times background and showed no clear dose-response
relationship. NMP was evaluated in another Ames assay using several S. typhimurium strains both with
and without metabolic activation and was determined to be negative (Mortelmans et at.. 1986).
NMP was evaluated in an HGPRT assay using Chinese hamster ovary cells at concentrations ranging
from 0.5 to 5.0 mg/ml (with and without S9 mix) and showed no cytotoxicity and did not increase the
mutation rate (GAF Corp., 1988; TSCAT, 1990b) as cited in OECD (2007b). Mayer et al. (1988)
reported that NMP induced a dose-related increase in the aneuploidy rate in yeast at concentrations in
the range of 154.0 to 229.3 mM. However, OECD (2007b) noted that these dose levels were clearly
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cytotoxic in a dose-dependent manner and determined the study to be invalid by stating it was a
biological system of little relevance. Furthermore, OECD has deleted test guidelines using yeast because
tests for mammalian cells are preferred (OECD. 2.017).
In a mouse lymphoma test in the L5178 Y cell line with concentrations of 0, 1,000, 4,000, 8,000 or
10,000 ppm (v/v) without/with S-9 mix, NMP showed good solubility and revealed no cytotoxicity or
mutagenic response at any concentration (E.I. du Pont de Nemours and Company, 1976, TSCAT,
1990c[sic]) as cited in OECD (2007b).
NMP was evaluated (to determine its ability to interact with DNA) in an in vitro assay with primary
hepatocytes from the liver of an untreated male F-344 rat. Test concentrations ranged from 250 - 5000
|ig/ml, NMP was shown to be soluble and slightly cytotoxic at concentrations 4.ooo |ig/ml. NMP did
not induce significant changes in nuclear labeling of rat primary hepatocytes ill concentrations ranging
from 500 - 5,000 |ig/ml, covering a wide range of cell sin \ ival (53.2% - 98.6%, (i Al Corp., 1988b;
TSCAT, 1990b; Vetline Inc., 1988) as cited in OECD O'.w/o).
Table 3-5. Summarv of Tn Vitro Genotoxicitv Studies
liioassav
l est system
Concent ration
With/without metabolic
activation (+/- S9 mix)
Result
Remark
Reference
Ames lesl,
S. typhimurium
(TA98, TA100,
TA1535, TA1537),
3 15 3<)<)<)<) ill plale
(+/- S9 mix)
ncuali \ e
Standard plate
lesl
li \SI \(i.
1978a
Ames test,
S. typhimurium
(TA97, TA98,
TA100, TA1535,
TA1537)
I) |()() |()()() 3"n
| oooo liu pliile
( - Sl) mi\)
negative
Preincuba-tion
assay,
Compara-tive
study within
NTP testing
Mortelmans et
al., 1986
Ames test.
S. typhimiirmm
(TA97, T.VJ8,
TA100. TAI02.
TA104, T \2(->3S,
UTH84I3.
UHT8414)
mil 1 "ion uM pUiic
( - Sl) mi\)
negative
Standard plate
test
Wells et al.,
1988
Ames test,
S. typhimurium
(TA98, TA104)
<~)o| 1000 |iM/pl ate
( - Sl) mix)
negative
Preincuba-tion
assay
Wells et al.,
1988
HGPRT test,
CHO cells,
0.5-5.0 mg/ml
(+/- S9 mix)
negative
GAF Corp.,
1988;
TSCAT,
1990b
Mouse lymphoma
assay,
1000 - 10000 ppm (V/V)
(+/- S9 mix)
negative
E.I. du Pont
de Nemours
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liiosisssiv
l est system
CoiKTiilrsilion
With/without melnholic
ion (+/- S9 mix)
Result
Ueinsirk
Reference
L5178Y cells,
and Company,
1976;
TSCAT,
1990b
UDS,
Rat primary
hepatocytes,
250 - 5000 |ig/ml
negative
GAF Corp.,
1988b;
TSCAT,
1990b;
Vetline Inc.,
N88
Source: OECD (2007b'). Table 8, pp. 30-31; All references are as cilal in OECD (2007b)
\Jo clastogenic or aneugenic potential of NMP was reported for somatic or germ cells in in vivo studies.
For some genetic endpoints examined in vitro (e.g., point mutations, DNA damage and repair), NMP
also showed negative responses in several bacterial and mammalian test systems. A positive result for
aneuploidy in yeast was determined to be invalid by OECD ( ).
Other Mechanistic Studies
The effect of NMP on cell proliferation in 1he I i \ er (S-phase response) after one or four weeks of dietary
exposure at 7200 ppm (1392/1906 mg/kg bw day in males females) using B6C3F1 mice was
investigated. Incorporation of bromodeoxyuridine (HidI ) into li \ er DNA was examined
microscopically. The cell proliferation rate in liver increased (•> lMbld in treated males and 3.3-fold in
treated females as compared to untreated control animals. Males (9,10) also exhibited minimal to slight
centrilobular hepatocellular hypertrophy as compared to females which showed an incidence of l/10for
this effect.
Males showed a 2.1-fold increase in cell proliferation rate in liver; a 1.7-fold increase was observed in
females. An increase in the incidence of apoplolic liver cells was observed in males only, with minimal
to slight centrilobular hypertrophy recorded in 7/10 male and 2/10 female mice, respectively. In
conclusion. NMP induced increased hepatocellular proliferation after dietary exposure for one or four
weeks (NMP Producers Group, 2002b) as cited in OECD (2007b).
NMP was in\ estimated for its ability to induce liver enzymes or peroxisome proliferation in B6C3F1
mice treated at 72<)<) ppm via the diet (1364/1945 mg/kg bw/day in males/females). This dose was also
shown to increase li\ er tumors in mice. The livers taken from 10 animals per sex were examined for
cytochrome P450-content. and enzyme activity (ethoxyresorufin-O-deethylase (EROD) and
pentoxyresorufin-O-depentylase (PROD)). In addition, 5 male and 5 female mice were examined for
treatment-related changes in cyanide-insensitive Palmitoyl-CoA-oxidation (PALCoA) and
histopathology, including changes in peroxisomes, endoplasmic reticulum or mitochondria. NMP
exposure resulted in a slight increase in the activity of PALCoA in male animals; electron microscopy
also revealed a slight elevation in peroxisomes in 2/5 males (NMP Producers group, 2002a) as cited in
OECD (2007b).
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Conclusions
NMP has been evaluated in several in vitro and in vivo genotoxicity assays that cover a range of
endpoints, including chromosomal aberration, DNA damage and repair, and point mutations. Negative
results in these mammalian and bacterial test systems representing multiple endpoints indicate that NMP
is unlikely to be genotoxic.
3.2.3.2.2 Carcinogenicity
In a 2-year inhalation cancer bioassay, Sprague-Dawley rats (120 per sex per concentration) were
exposed in a whole-body experiment to NMP vapor concentrations of 41 and 405 mg/m3 (0, 10 and 100
ppm) for 6 h/day, 5 days/week. Survival of treated rats did not differ from controls. Other than an
increase in pituitary adenocarcinomas at 41 mg/m3 at 18 months but not at 405 mg/m3 or at 24 months,
there were no increases in incidence of benign or malignant tumors at any concentration ( ; et at..
1987; DuPont. 1982V
In an oral dietary study, NMP was examined for its chronic toxicity and carcinogenic potential in groups
of 62 male and 62 female Sprague-Dawley rats at concentrations of 0, 1600, 5000 or I 5<)()i) ppm (about
66/88, 207/283, 678/939 mg/kg bw/day, males/females) in food for two years. The survival of female
rats was not affected, but males in the high dose group had low er sur\ i val due to increased severe
chronic-progressive nephropathy. The incidence of benign or malignant tumors was not increased
among rats (Maltey et at.. 2001; NMP Pr 7)
NMP was also administered to groups of 50 male and 5<) female IJOC3F 1 mice receiving dietary
concentrations of 0, 600, 1200 and 7200 ppm (about 115. I 73 221, 1089/1399 mg/kg-bw/day,
males/females) in an 18-month study There was no difference in survival of treated mice compared with
controls. Among the 7200 ppm males, incidences of liver carcinomas were increased, whereas the
incidence in females was within the historical control range. Increased incidences of liver adenomas
were also noted at 7200 ppm; these occurred in both sexes. NMP also caused other substance-related
effects in the liver at 1,200 and 7,200 ppm For example, increased metabolic activity was observed. In
addition, mice exhibited increased li\ er weights and incidences of foci of cellular alteration in the liver
at 7200 ppm in both sexes In the 12<)<) ppm group, increased liver weights were also observed among
males and 3 50 of the mice exhibited centri lobular liver cell hypertrophy (Mattey et at.. 2001) and NMP
Producers (iroup, 1999a, as cited in Ol-('l) ( 307b). Results of cancer bioassays for NMP are
summarized in Table 3-6.
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Table 3-6. Summary of Tumor Incidence Data from Cancer Bioassays
Species/St rsiin/
Sox (Nilmher/
"roup)
Kxposnre
Route
Doses/
Concentrations
Duration
Cancer
Incidence
I! ITec I
Reference
Data
Quality
K\;ilu:ilion
Rat/Cij:
CD(SD)/ Both
(120)
Inhalation,
whole
body
0, 41, 405 mg/m3
6 hrs/day
5
days/wee
k
for 2
years
Summary
data not
presented
Increased
pituitary
adenocarcin-
omas at 41
but not 405
mg/m3 and at
18 bill not 24
months
DuPont
(1982)'
Rat/Other/
Female (62)
0, 87.8, 283,939
mg/kg-bw/day
(0, 1600, 5000,
15,000 ppm)
2 years
i). 2. 3. 3
At least one
mammary
neoplasm
Mouse/B6C3F1/
Male (50)
Oral.
dietar\
0, 89, 173, 1089
nig kg-bu da\
((Tnio. 12()(i.
72()() ppm)
5,2,4. 12
Increased
incidence of
hepatocellular
adenoma
4. 1.3. 13"
IS
months
Increased
incidence of
hepatocellular
carcinoma
Malley et
al.
(200 :nb
Mouse/B6C3F
1/Female (50)
i). I 15. 221.
I.?w
mu ku-bu cla\
(n. ono. |2i)i).
72i)i) ppm)
2.2, 1,7'
Increased
hepatocellular
adenoma and
carcinoma
o. 0, 0, 3
Increased
hepatocellular
carcinoma
a This is i lie unpublished siud\ oi l he published study identified as Lee et al.
b Unpublished results in rats are available as W1I' Producers Group (1997):
Group. 19'W;i. ;is eited in OECD ( ')
0 p < 0.05 b\ ('nehrcin-Armitage trend test
(.1.987)
the unpublished mouse study is NMP Producers
3.2.4 Weight of Scientific Evidence
The best available human health hazard science was selected for dose-response modeling based on
integrating the results of the data evaluation and weight-of-the-scientific evidence. Other recent
assessments (EC. 2016: Danish Ministry of the Environment 2015: U.S. EPA. 2015: NICNAS. 2013:
OECD. 2009b: U.S. EPA. 2006b: WHO. 2001) have previously evaluated the weight of scientific
evidence and identified reproductive and developmental toxicity as the most sensitive health effects
associated with exposure to NMP. This section therefore focuses on the weight-of-the-scientific
evidence for reproductive and developmental toxicity for both short-term and chronic exposures.
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3.2.4.1 Weight of Scientific Evidence for Developmental Toxicity
A review of the reasonably available information shows comparable effect levels for developmental
toxicity, with NOAELs typically ranging from 100-200 mg/kg-bw/day reported in oral exposure studies
and effect levels ranging 479-612 mg/m3 reported in the inhalation exposure studies. EPA identified
sensitive and biologically relevant effects that occur along a continuum of reproductive and
developmental toxicity, including decreased fetal and pup body weight, delayed ossification, skeletal
malformations and increased fetal and pup mortality. These endpoints are discussed in more detail
below.
A well-documented case report provides qualitative support for results in laboratory animals indicating
that NMP may be detrimental to mammalian development. Tn this case report, a pregnant woman who
was exposed to NMP at work via dermal and inhalation exposure aborted at week 3 I of pregnancy.
Although the precise exposure levels are unknown, she reportedly cleaned up an NMP spill that
dissolved her latex gloves during week 16 of the pregnancy She was ill for the next lour days and
experienced malaise, headache, nausea and vomiting (5 on et al., 1996). Although this study
provides some evidence that NMP may harm the developing conceptus, the lack of quantitative
exposure data precludes its use for quantitative risk estimation
Becci et al. (1982) reported adverse developmental effects in Spiauue Dawley rats following NMP
exposure via dermal administration. Dams were exposed to NMP al <>. 75. 237 or 750 mg/kg-bw on
gestation days (GD) 6-15. All animals were killed and subjected to uterine examination on day 20 of
gestation. Treatment at 750 mg/kg-bw was associated with significant decreases in maternal body
weight gain, and live litter size, as well as an increased incidence of resorptions and skeletal anomalies.
No evidence of teratogenic or maternal effects was observed at 75 or 237 mg/kg-bw; the NOAEL for
maternal and developmental toxicity was 237 mg/kg-bw.
Developmental toxicity was reported in Sprague-Dawley rats after NMP exposure via gavage
administration (SaiiK i ^ ; ^ ;¦) Pregnant rats were dosed at 0, 125, 250, 500, or 750 mg/kg-bw
on GD 6-20. All animals were killed and subjected to uterine examination on day 21 of gestation. A
dose-related decrease in fetal body weights (males, females) was observed at all doses, reaching
statistical significance at 25<"> mg/ku-hw Significantly decreased maternal body weight gain/food
consumption and an increased incidence of post implantation loss/fetal resorption and fetal
malformations were reported at doses _ 5<)0 mg/kg-bw; observed treatment-related anomalies included
imperforate anus, the absence of a tail and malformation of the spinal column, heart and/or great vessels.
TheNOAI-l.s lor maternal and developmental toxicity were 250 and 125 mg/kg/day, respectively.
The developmental toxicity of WIP was also studied in Sprague-Dawley rats after whole body
inhalation exposure ( et al.. 2003). Pregnant rats were exposed to NMP vapor at 0, 30, 60 or
120 ppm (0, 122, 243 and 487 mg/m3 nominal concentration), 6 h/day, on GD 6-20. Maternal body
weight gain was significantly decreased at 60 and 120 ppm during the first half of exposure (GD 6-13)
and maternal food consumption was reduced at 120 ppm on GD 13-21; however, no significant
difference in the gestational weight change of treated dams was observed when maternal body weight
was corrected for gravid uterine weight. No evidence of teratogenicity was observed at any
concentration tested. Fetal toxicity, as evidenced by dose-related decreases in fetal body weight (males,
females) was observed at all doses tested, reaching statistical significance at 120 ppm (5-6% reduction in
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body weight relative to controls). The NOAEC for maternal and developmental toxicity were 30 and 60
ppm, respectively.
These findings are consistent with reports of fetal growth retardation and the absence of teratogenic
effects in previous studies of the developmental toxicity of inhaled NMP. In a two-generation
reproduction study, Sprague Dawley rats were exposed to NMP via (whole body) inhalation at 116 ppm,
6 h/day, prior to mating and throughout gestation and lactation (Solomon etal. 1995). Half of the dams
were subjected to cesarean section on GD 21 and the remaining litters were evaluated up to weaning. No
adverse effects on offspring viability or morphology were reported other than a decrease in fetal and pup
body weights. Hass et al. (1995) exposed pregnant rats via (whole body) inhalation to 165 ppm NMP, 6
h per day, from GD 4-20. Delayed skeletal ossification and decreased fetal body weights were reported
in offspring of treated dams following NMP exposure. In a previous study, (w hole body) inhalation
exposure to Wistar rats at 150 ppm NMP on GD 7-20 resulted in significantly decreased pup body
weights that persisted from birth until 5 weeks of age \o signs of maternal toxicity were observed in
either study (Hass et al. 1994).
Mortality and structural malformations have been detected in rats following high levels of NMP
exposure via dermal (Becci et al.. 1982.) and gavage administration (Saillenfait et al.. 2002). Differences
in the developmental response to NMP may be ascribed in part, to quantitative and/or qualitative
differences in the exposure of the embryo/fetus by route of administration. Studies in humans and rats
indicate that NMP is readily absorbed by all routes of exposure and extensively metabolized prior to
excretion in urine; however, the peak concentration and residence time of the parent compound may
vary depending on the route of exposure and the metabolic "status" of the exposed individual (Jonsson
and Akesson. 2001; 20-'-:-: il A 2000; Akesson ana Ji \|7; Ursin et al.. 1995; Midglev
etal. 1992).
NMP and its metabolites were evaluated for potential embryotoxicity using the rat whole embryo culture
(WEC) and the BALB/c 3T3 cytotoxicity test (I'lick - ; w . 009). The resulting data were evaluated
using two strategies; one based on all end points e\ aluated in the WEC and the other included endpoints
from both the WEC and a cytotoxicity test Based on the reported results, the substance with the highest
embryotoxic potential was W1P, followed by 5-hydroxy-N-methyl-pyrrolidone (5-HNMP), 2-hydroxy-
N-methylsuccinimidc (2-1IMSI) and Vmethylsuccinimide (MSI). Developmental anomalies induced by
NMP and 5-1 [NMP include aberrations in the head region of the embryos, abnormal development of the
second branchial arches and open neural pores. Only NMP and 5-HNMP induced specific embryotoxic
effects, w hereas the other two metabolites, 2-HMSI and MSI, were determined to be non-embryotoxic.
EPA assessed risks lor adverse de\ elopmental effects within the context of the exposure scenarios
identified in the exposure assessment, as summarized in Table 3-7.
3.2.4.1 Weight of Scientific Evidence for Reproductive Toxicity
A review of the reasonably available scientific information identified decreased male and female fertility
and testicular lesions and atrophy as potential reproductive effects of NMP exposure. Effects on fertility
have been reported at doses lower than those associated with developmental effects, but are less
consistently observed across studies than developmental effects.
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Three oral exposure reproductive studies reported reduced fertility or reproductive success. Sitarek et al.
(2012) reported a decrease in the number of pregnant female rats following oral gavage exposure to 450
mg/kg-bw/day five days a week for two weeks prior to mating. This study identified a NOAEL of 150
mg/kg-bw/day for reproductive toxicity. Another study focused on effects of paternal exposure via oral
gavage. Paternal NMP exposure for ten weeks prior to mating and during mating was associated with
reduced male fertility (NOAEL = 300 mg/kg-bw/day) and decreased viability of offspring in the first
four days of life (NOAEL =100 mg/kg-bw/day) (Sitarek and Stetkiewicz 9ilft8).
In a two-generation study, Exxon Biomedical Sciences (1991) reported significant decreases in male
fertility and female fecundity as well as reduced survival and growth rates in offspring following oral
dietary exposure to 500 mg/kg/day beginning ten days prior to conception and throughout gestation and
lactation. In the second generation (rats exposed throughout development and as adults during mating),
significant reductions in male fertility and female fecundity were reported at all doses At 50 mg/kg-
bw/day, the lowest dose tested, male fertility decreased I S-28% and female fecundity decreased 18-20%
relative to controls. Study authors concluded that these statistically significant effects were not
biologically significant at low and mid-range doses because they were "within or close to historical
control ranges" and identified a NOAEL of 160 mg/kg-bw/day for reproductive effects. However,
historical control data from the performing laboratory were not provided. EPA considered these
significant reductions in male fertility and female fecundity rehiti\ e to concurrent controls biologically
relevant and identified the lowest dose tested. 5<) mu kg/day, as the I .OAI-L for reproductive effects.
In reviewing the findings from Exxon (11..,). N\\ also considered limited published historical control
data (HCD) for Sprague-Dawley rat male and female fertility in reproductive toxicity studies, as well as
available online information from a contract research laboratory (CRO) (•"Varies River. 2018). These
sources reported mean male HCI) fertility indices of 86.4% in second generation males from 27
reproduction studies (Marty et al . 2<)()9, 1580376) and 94.1%> from 208 studies (4359 rats) assessed by
the CRO (Charles Rr ,J:; ) Mean female HCD fertility indices were 87.5% in second generation
females from 27 studies reported by Marty et al (2C; ;), and 93.9% from 211 studies (4854 rats)
evaluated by the CRO. These data support the I -PA interpretation of the Exxon (1991) fertility data,
although it is acknowledged that appropriate IICI) data from the performing laboratory are preferred for
use in data interpretation ( ).
Other two-generation studies did not replicate effects on reduced fertility. Two two-generation guideline
dietary exposure studies in rats reported no adverse reproductive effects at the highest doses tested (500
mg/kg/bw/day. subsequently reduced to 350 mg/kg-bw/day due to pup mortality) (N >ducers
Group. 199S . ) I-PA has reviewed summaries of these two unpublished two-generation studies
(RIVM. 2013; C I07h) but data in these reports are not publicly available and EPA does not have
complete access to the full reports. EPA is therefore unable to evaluate study quality or incorporate
quantitative information from these studies into the dose-response assessment. A two-generation whole
body inhalation exposure study in rats also found no effects on fertility or fecundity following exposure
to 10, 51, or 116 ppm NMP for 6 hr/day, 7 days/week prior to mating, and during mating, gestation, and
lactation (Solomon et al.. 1995). However, the second-generation rats were not exposed from weaning to
mating, and the F1 adults were mated with a cohort of untreated rats. In addition, there were
uncertainties related to actual exposures achieved in this study.
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Several oral repeated-dose studies detected testicular lesions and smaller testes (atrophy). A four-week
oral exposure study identified a NOAEL of 429 mg/kg-bw/day for testicular lesions and atrophy (Malek
et ai. 1997) while a two-year oral exposure study in rats identified a NOAEL of 207 mg/kg/day for
testicular lesions and atrophy (Malley et at.. 2001). The same study observed no effect on testicular
atrophy in mice. In a third oral exposure study, male mice were exposed to NMP for ten weeks prior to
mating and during mating. This study reported cellular depletion of seminiferous tubule epithelium and
reduced male fertility at 1000 mg/kg-bw/day, but not at 300 mg/kg-bw/day (Sitarek and Stetkiewicz.
2008).
Other studies reported no effect on male reproductive endpoints, including a three month oral exposure
in beagle dogs (NOAEL = 246 mg/kg-bw/day) (Becci et ai. 19:-: ) and a '•><> day oral exposure study in
rats (NOAEL = 1057 mg/kg-bw/day) and mice (NOAEL = 193 1 mg/kg-bu day) (Mallev et ai. 1999)
and a chronic inhalation study in rats (NOAEL= 100 mg/kg-bw/day) (DuFon )
EPA assessed risks for adverse reproductive effects within the context of the exposure scenarios
identified in the exposure assessment, as summarized in TaMe 3-7
Table 3-7. Summary of Exposure Pathways and Toxicity Kndpoints used lor Risk Evaluation
Receptors
Kxposurc Pathway and Analytical Approach
Acute Dermal and Inhalation
Kxposurcs
Chronic Dermal and Inhalation
Kxposurcs
Worker
Users and
Nearby
Worker
Non-Users
Toxic endpoint l)e\ elopmental toxicity ¦'
Risk approach: Margin of Lxposuic (MOL)
Toxic l-iulpoint Reproductive toxicity
(fertility de\elopmental)
Risk approach: iVIargin of Exposure (MOE)
Consumer
Users and
Nearby
Residenlial
Non-Users
Chronic risks were not evaluated. This
pathway was not expected to occur in
consumer users or bystanders.
a Acute dermal and inhalation toxicity studies were not used because they typically measure lethality at
high doses and do not pro\ ide the level of analysis to assess non-effect levels from single exposures.
3.2.5 Dose-Response Assessment
This section identifies the endpoints EPA selected for risk estimation. Available studies were reviewed
based on study design, analysis and reporting quality to evaluate their individual strengths and
weaknesses as summarized in Section 0. Guideline studies and other protocols that utilized good
laboratory practices were considered if they met PECO and study quality criteria. The selected studies
were then evaluated in the dose-response assessment.
Effects observed in multiple studies that were determined to be sensitive and biologically relevant, were
considered for points of departure (POD) and dose-response analysis. These endpoints include:
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• Decreased fetal/pup weight, PND 0, 4, 21
• Increased fetal/pup mortality, PND 0, 4, 21
• Skeletal malformations and incomplete skeletal ossification
• Reduced male and female fertility
Although it is unclear whether fetal effects are secondary to maternal toxicity, NMP can cross the
placenta ( .. 2013); therefore, EPA considers the fetal effects observed following NMP exposure to
be biologically relevant.
Numerous studies are available to assess the developmental effects of \ \lP exposure in rats. Most are
based on oral exposure, although some administered NMP via inhalation route One study evaluated the
developmental effects following dermal exposure to rats. Table 3-8 summarizes the developmental
endpoints evaluated in the studies reviewed for this assessment. Although de\ elopmental outcomes may
vary due to temporal variations in vulnerability, EPA considers the general consistency of outcomes
observed across different species, routes, durations and windows of exposure to be supportive of the
robustness of this treatment effect.
Several studies are available to assess the reproductive effects of NMP exposure. While reproductive
effects are less consistently reported across studies than developmental effects, reduced fertility
following exposure throughout gestation, lactation, growth, puberty, and prior to mating is a particularly
sensitive endpoint. It is consistent with reduced fertility observed at higher doses following exposure to
NMP prior to mating. Table 3-9 summarizes the effects on fertility obser\ ed in studies considered in this
assessment.
Table 3-8. Evidence for NAlP-induced Developmental Toxicity
Sluclj
Diilii
Qn;ili(\
Score
I-CI ill
Weigh!
CI) 20-
PNI) 1
Pup
\\ eight
I'M) 4
Pup
Weigh!
I'M)
21
I-CI ill
Moriiilil>
¦' (multiple
mclrics)
Pup
Moriiiliit
PNI) 4*
Pup
Morliililt
PND 2l"
Incomplete
Ossil'iciil ion
Skclcliil
Miill'onil ill ions
(
)
Midi
--
4
1
t
t
t
NA
NA
( and
)
High
NA
NA
NA
--
t
--
NA
NA
ORAL
STUDIES
(NL.
lucei
Grout).
1999a)c
Not
ruled
1
1
t
t
t
(NMP
lucers
Grout).
1999bV
Not
rated
1
1
t
t
t
(Saillenfait
et al. 2002)
High
4
NA
NA
t
NA
NA
t
t
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Siuclj
Diilii
Qnali(\
Score
I-01 ill
Wcifihl
CI) 20-
PNI) 1
Pup
Wcifihl
I'M) 4
Pup
WeiiilK
PM)
21
I-Ol ill
Mnr(ali(\
¦' (multiple
metrics)
Pup
Moriiilii>
PNI)4
Pup
Moriiilii>
PNI) 21
liicdinpkMo
Ossiliciilidii
Skek'liil
MiiHoriiiiilious
(
iyyz>
High
1
NA
NA
--
NA
NA
T
~
INHALATION
STUDIES
(Saillenfait
et al.. 2003)
High
4
NA
NA
~
NA
NA
~
~
(Hass et al..
1995/
Not
rated
4
NA
NA
t
NA
NA
t
~
(Hass et al..
1994)d
Not
rated
4
4
4
~
~
~
NA
NA
(Solomon et
al.. 1995;
DuPont.
1990)
High
4
4
4
-ph
~
~
T
t
(Lee et al.
1987)
High
--
NA
--
NA
~
--
DERMAL
STUDIES
(Becci et
al.. 1982)
Medium
4
NA
T
NA
NA
NA
t
t
i indicates decrease, t indicates increase. ~ indicates no cliauue
aMay be based on resorptions, posi-iniplauialioii loss. doadpiips> at birth or decreased live pups at birth
b Statistically significant increase lor p t) 1
0 Studies not rated because EPA does not ha\ e access in ilie complete study report. These studies are included here because
previous assessments have cited them as suppniliuu siiidics and they contribute to overall weight of evidence.
d Studies not rated because i he> were excluded by the PECO statement in the systematic review process due to the lack of
dose-response information i ilie siud\ used a sumle high dose). These studies are included here because previous assessments
have cited them as suppoiliim siudies and llie> contribute to overall weight of evidence.
NA = Not \ssessed
Blank = Dala not publicly available
4379
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Table 3-9. Evidence for NMP-induced Reproductive Toxicity
Study
Diitii
Quality
Score
Effects followiu» adult
exposure
Effects follow
tliroiiulioiit i
in» exposure
c\clopmcnr'
Male fertility
Eeinale
fecund it v
Male fertility
I'emale
fecundity
ORAL
STUDIES
(Exxon. 1991)
High
—
—
4
1
(Sitarek et ala
2.012)
High
NA
4
NA
NA
(Sitarek and
Stetkiewicz.
2008)
High
4
NA
NA
NA
(NMP
Producers
Grout; ilii!')a)b
Not
available
(NMP
Producers
Grouv i f )b)b
Not
available
INHALATION
STUDIES
(Solomon et
al. 1995;
DuPonl 1990)
High
--
--
--
--
I indicates decrease, t indicates increase. ~ indicates no chaimc
aIn Exxon 1991 andtheNMP Producers (uoup I ''99 studies. reproductive effects in the second generation were
evaluated following exposures throughout uestalinti, lactation. mow 111. puberty and adulthood prior to mating. In
the Solomon et al 1995/Dupont 1990 studs. second generation rats were not exposed after weaning and exposed
rats were mated with unexposed controls
b Studies not rated because EPA dues uoi h;i\ e access lo I he complete study reports. These studies are included
here because previous assessment ha\ e ciled llieni as supporting studies and they contribute to overall weight
of evidence.
NA = Not Assessed
Blank = Data not publicl\ a\ ;nl;ihle
3.2.5.1 Selection of Endpoints for Dose-Response Assessment
Decreased fetal/pup weights
Decreased fetal and, or postnatal hody weights were consistently observed across studies despite
variations in dosing time and exposure routes. The fetal and postnatal body weight effects noted in Table
3-8 were plotted graphically in exposure-response arrays (Figure 3-2 and Figure 3-3). Exposure-
response arrays are a graphical representation of available dose-response data for significant effects.
Included in the exposure-response arrays are LOAELs and NOAELs, based on applied doses. The
graphical display allows the reader to quickly compare study outcomes, based on the same or groups of
related endpoints for growth and development. In this case, the exposure -response arrays illustrate the
concordance and consistency of these effects - meaning that the effects were present in multiple studies
and the NOAELs and LOAELs occurred within a narrow dose range.
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As illustrated in Figure 3-2, fetal body weights were decreased with oral (gavage) exposures in several
rat studies. Saillenfait (2002) reported fetal body weights decreased by 10% at 250 mg/kg-bw/day and
by 47% at the highest dose, 750 mg/kg-bw/day. In the Exxon (1992) study, fetal body weights decreased
by 10-11% at 400 mg/kg-bw/day, the highest dose tested. Sitarek et al. (2012) observed 25-30%
decrements in pup body weight (PND 4) following maternal exposure to concentrations >150 mg/kg-
bw/day. Because the Sitarek study involved maternal exposures that continued through the postnatal
period, the significant decreases in pup body weights observed at PND 4 but not at PND 1 might have
been due to toxicity resulting from prenatal exposure to NMP and/or as a result of postnatal transfer of
NMP to the pups via lactation.
Figure 3-3 presents the exposure-response array for the inhalation studies in rats Statistically significant
decreases in body weights were observed following inhalation exposure at concentrations ranging from
479 to 612 mg/m3 in multiple studies (Saillenfait et al... 2003; Hass et al.. 1995; ctai. 1994;
DuPc €). Saillenfait et al. (2003) observed 5-6% decrements in fetal body weights at 486 mg/m3
and DuPont (1990) observed 7% decrements in fetal body weights at 479 mg/m3. Two studies by Hass et
al- (1995; 1994) also indicated that fetal body weights were decreased in both Wistar and Sprague-
Dawley rats; however, both of the Hass studies were excluded by the systematic review process for
selection of candidate PODs for this risk evaluation because only one dose level (612 mg/m3) was used
in each study. They are included here because they are used as supporting studies in several previous
assessments (\_v < J ^ s , 1V 201"). and lhey contribute to the overall weight of evidence. In
contrast, no changes in fetal body weight were observed in a study by ( ; tl.. 1987).
The DuPont and Hass studies also noted decreased pup body weights (t et: al.. 1995; Hass et al..
1994; DuPont 1990). In the DuPont study, exposures were suspended from GD 20 through PND 4, but
the weight decrement remained, lending support to the notion that decreased body weight is a persistent,
adverse effect.
Based on the observations of decreased fetal and postnatal body weights, EPA considered decreased
fetal body weights as a potential key endpoint lor use in the risk calculation for chronic exposure. These
effects were consistent among multiple studies with different dosing regimens and across exposure
routes. Reduced fetal body w eight is a sensitive endpoint that is considered a marker for fetal growth
restriction which is often assumed to be representative of repeated dose rather than acute exposures (van
Ra; i: )03). Decreases in letal and postnatal body weights occur at similar dose levels. Decreased
fetal body weight was assumed to be the proximate event. In a previous risk evaluation, EPA used this
endpoint as the basis for evaluating chronic risks ( 315).
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re
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1
bfl
E
m
§
Q
2
O
exposure
duration
specie
strain
endpoint
(timing)
decreased fetal/pup
BW or fertility in rats
1000
100
10
A
~
LOAEL ~ Doses < NOAEL
~ .
A
C4
iH
r-f
O
o
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03
03
E
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-iii
W
u.
.
*
9 wks
gavage
Rat. Wist
9 wks
gavage
¦ .'/istar
fetal bw{GD21)
pup bw
(PND 1)
pup bw
(PND 4)
9 wks
gavage
Rat, Wistar
pup bw
(PND 21)
2 gen
dietary
Rat, SD,
male
a
fertility
(adult)
2 gen
dietary
Rat, SD,
female
fecundity
(adult)
1000
5
s®
E
.2
ro
O
o
c
o
u
0>
h.
3
(0
E
k.
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1000
decreased fetal/pup
BW or fertility in rats
~ LOAEL A NOAEL
¦ Doses > LOAEL ~ Doses < NOAEL
100
10
c
(V
u
0)
3
A
A
~
~
A
A
A
A
A
A
A
~
exposure
duration
species,
strain
endpoin!
m
8
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tn
§
a
fetal bw (GD 21}
z
r
r
c
o
~l
zs
3
)[) / 20
Rat,
Wistar
(PND 1)
2 gen
Rat, CD
GD 7-20
Rat,
Wistar
pup bw (PND 4)
2 gen
Rat, CD
01
01
©
in
in
CO
X
o
CTI
CD
c
o
CL
3
Q
GD 7-20
Rat,
Wistar
2 gen
Rat, CD,
male
pup bw (PND 21)
fertility
(adult)
fecundity
(adult)
Figure 3-3. Studies that Measured Reproductive and Developmental Effects after Repeated Dose
Inhalation Exposure.
Note, the Hass 1994 and I lass 1995 studies were screened out in systematic review because they evaluated effects of a single
dose. They were not c\ alualcd for study quality, but they are included here as part of the weight of evidence. The Dupont
1990 study (Solomon et ah, 1995: DuPont. 1990") was rated a high-quality study, but it is not consistent with guidelines for 2
generation studies and there were uncertainties about the actual doses achieved at the highest exposure.
Resorptions and Fetal Mortality
Fetal resorptions have been observed in oral, inhalation and dermal studies (Saillenfait et at.. 2002; EI
Dupont De Nemours & Co. 1990; Becci et ai. 1982). Fetal and postnatal mortality have also been
observed in oral and dermal studies (Sitarek et at.. 2012.; NMP Producers Group. 1999a. b; Becci et at..
1982). Statistically significant increases in resorptions or mortality were seen consistently at
administered doses of 500 - 1000 mg/kg-bw/day in all studies at the tested doses.
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In the single dermal study fetal/pup mortality was increased at 750 mg/kg-bw/day (Becci et at.. 1982). In
inhalation studies with exposures up to the air saturating concentration, statistically significant increased
resorptions or fetal and postnatal pup mortality were not observed, possibly due to the limited NMP
exposure concentration. Resorptions and mortality can occur following a single exposure during a
sensitive developmental stage and as such, resorptions and fetal and postnatal mortality are considered a
relevant endpoint for acute effects (van Raaii et at.. 2003).
EPA also considered the relevance of increased postnatal mortality observed in the Sitarek et al. (2012)
and NMP Producers Group (NMP Producers Group. 1999a. b) studies Thi s outcome was not
consistently observed in other studies: Sitarek et al. (2012) observed increased pup mortality at 150
mg/kg-bw/day, the NMP producers group studies did not see increased pup mortality until 350 mg/kg-
bw/day and no increase in pup mortality was observed in DuPont ( ). W hen increased post-natal
mortality was observed, the NOAELs were within the same range as other sensiiive endpoints, such as
reduced fetal body weight (e.g., see Table 3-2).
EPA selected increased fetal resorptions/fetal mortal ily as a key endpoint for the calculation of risks
associated with acute exposures. Fetal resorptions (mortality) may result from a single exposure at a
developmentally critical period (Davis et at.. 2009a; van Raaii et al.. 2u ; \ I J b). In the
studies reviewed, increased fetal mortality occurred at relatively low exposures, suggesting that this was
a sensitive and relevant endpoint, suitable for use in the risk assessment
Other Fetal Effects
Incomplete ossification was observed following exposures to NMP via oral, inhalation and dermal
routes. Incomplete ossification is a decrease in the amount of mineralized bone expected for
developmental age and is one of the most common findings in de\ elopmental toxicity studies (Carney
and Kiromet. 2007). Saillenfait et al ( ') reported statistically significant increases in incidences of
incomplete ossification of sternebrae. skull and thoracic vertebral centra at GD 20 for oral doses of 500
and 750 mg/kg-bw/day. Hass et al ( ) reported statistically significant increases in delayed
ossification of cervical vertebrae 4 through 7 and digital bones following an inhalation exposure at a
concentration of mg nr Bccci et al ( ) reported a statistically significant increase in incidences
of incomplete ossification of \ erlehrae at 75<~> mg/kg-bw/day dermal application. On the other hand,
several inhalation exposure studies found no increased incidence of incomplete or delayed ossification
(iyi 200J; < ! Oupont D irs & Co. 1990; Lee et al.. 1987).
The areas of increased incomplete ossification that were observed in fetuses at GD 20 or 21 were in
bones that are undergoing rapid ossification during the period of observation, but there are a number of
hormones considered to be important for regulating skeletal development (Carney and Kiroroet. 2007).
There are several clues that may be indicative of effects due to something other than generalized delay,
including: delays in the presence of specific skeletal malformations, teratogenesis or unusual patterns of
delayed ossification (C . . : and Kimmet. 2007; van Raaii et al.. 2003). Based on the absence of such
observations EPA considered NMP-associated delayed ossification to represent a continuum of effects
related to delays in fetal growth and development, associated with decreased fetal and/or pup body
weight.
Skeletal malformations are considered permanent structural changes that are likely to adversely affect
the survival or health of the species (Daston and Seed. 2007) and were observed in some NMP studies
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via oral exposure. The Saillenfait et al. (2002) study reported aggregated skeletal malformations
(including ribs, vertebrae and others) at GD 20 for oral doses of 500 and 750 mg/kg-bw/day. In contrast,
skeletal malformations were not observed in one dermal study and inhalation studies conducted up to the
air-saturating concentration. Increased skeletal malformations may not have been observed in the
inhalation studies because the vapor pressure of NMP limited the attainment of toxic concentrations in
air.
Reducedfertility
Reduced male fertility and female fecundity in the second generation of rats in a two-generation dietary
reproductive study (Exxon. 1991) were among the most sensitive reproductive and developmental
effects reported in the repeated dose studies reviewed for this risk evaluation (see Figure 3-2). Evidence
of reduced male fertility and female fecundity in this study is further supported In coinciding
observations of reduced litter size. It is unknown whether the fertility effects were initiated during
gestational, lactational, pubertal, growth, or adult exposures. While other two-generation studies failed
to replicate this effect (NMP Producers Group. Ivy-'.;. ! ). reproductive toxicity reported in Exxon
( ) is supported by evidence of effects on fertility follow ing pre-mating exposures in males and
female rats described by Sitarek et al. (2012; 200s). Reductions in offspring survival reported following
paternal pre-mating exposure (Sitarek and Stetkiewicz. ) indicate that reproductive effects may
include effects on gametes that impair offspring health and sur\ i\ al Reduced fertility may therefore be
considered part of a continuum of reproducli\ e and developmental effects of NMP exposure.
EPA considered decreased fertility a potential key endpoint for use in the risk calculation for chronic
exposures. Reduced male fertility and female fecundity were the most sensitive endpoints reported.
Observations from a 2-generation exposure study are supported by effects on male and female fertility
following adult exposures The previous EPA assessment (; : ; i ) did not characterize dose-
response for these fertility endpoints because the effect observed in the Exxon (1991) study was not
replicated in more recent 2-generation studies. However, EPA does not have complete access to the
studies that failed to replicate these findings ('•¦- YtP ]';• rs Group. 1999a. b), and cannot evaluate the
validity of the results. Re-evaluation of the I ¦won study demonstrates that the study shows a significant
effect in the most sensi ti \ e rep rod net i\ e and de\ elopmental endpoints identified in the available
literal lire
Key Endpoints
Developmental effects have consistently been reported following NMP exposure in laboratory animals
and a case report provides limited evidence of developmental toxicity in humans. In addition,
reproductive effects following NMP exposure have been reported in several animal studies. Collectively
the reported effects on reproduction and development, which include reduced male and female fertility,
decreased fetal and postnatal body weight, incomplete ossification, skeletal malformations and fetal or
postnatal mortality represent a continuum of biologically relevant outcomes that provide important
insights for hazard characterization. The developmental effects reported in different studies following
NMP exposure occur within a narrow dose range (i.e., 100 to 1000 mg/kg-bw/day for oral and 470 to
669 mg/m3 for inhalation exposures) and appear to persist based on clinical observations reported
through PND 21. EPA considers the general consistency of the NMP treatment effects reported across
studies to be supportive of the robustness of the developmental endpoints used for risk evaluation, which
exist along a continuum of adverse treatment effects. While reproductive effects are less consistent
across studies, reduced fertility is the most sensitive endpoint reported.
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EPA has selected fetal resorptions (mortality) as the basis of the dose-response analysis for acute
exposures. Acute toxicity studies observing other effects (e.g., LD50 values for acute toxicity or
lethality) were not used for the acute POD because the doses at which these effects were observed are
higher than those that caused toxic effects in developmental studies. Developmental studies involve
multiple exposures (i.e., test substance is administered for 10-15 days); however, they are relevant to
single exposures because some developmental effects, such as fetal resorptions and mortality, may result
from a single exposure at a developmentally critical period (Davis et at.. 2009b; van Raaii et at.. 2.003;
). In an analysis of the utility of developmental toxicity repeat dose studies for use in
the assessment of risks following acute exposures, van Raaij et al. compared the potency (NOAELs and
LOAELs) of developmental toxicity reported in repeated dose studies and single dose studies (van Raaii
et al.. 2003). Van Raaij et al. found that there is a relatively small difference between repeated and single
dose studies in the NOAELs and LOAELs reported for resorptions and re I tiled mortality events and
concluded that "resorptions observed in standard guideline based developmental toxicity studies are
considered to be relevant endpoints for setting limits for acute exposure." Consequently. EPA
determined that these endpoints are most applicable to assessing risks from acute exposures, where the
risk of their occurrence is assumed to depend on exceedtinee of a threshold value for even a single day
(i.e., peak concentration) rather than a time weighted average value and the magnitude of the exposure is
considered more important for these effects under these study conditions.
EPA selected reduced male fertility, female fecundity and reduced fetal body weights as the basis for the
dose-response analysis for chronic exposures Reduced fertility in male and female rats exposed
throughout development and prior to mating in a two-generation reproductive study was the most
sensitive reproductive and developmental endpoint identified in the available literature following
chronic exposures. Because NMP exposure in this study occurred throughout gestation, post-weaning,
growth, and prior to mating, it is unknown whether effects represent a developmental effect or whether
they are a result of subsequent exposures. Evidence for sensitive effects on fertility is complemented by
robust evidence of developmental toxicity. As documented above, reduced fetal body weight was
observed consistently across multiple studies with different dosing regimens and across exposure routes.
Reduced fetal body weight is a sensitive endpoint that is considered a marker for fetal growth restriction
typically resulting from repeated dosing during gestation rather than a single acute dose (van. Raaii et al..
2003). Together, these observations indicate a continuum of reproductive and developmental effects
associated with NMP exposure EPA therefore performed dose-response analysis on all three of these
reproducti\ e and developmental endpoints (male fertility, female fecundity, and fetal body weight) for
consideration as the chronic POD.
3.2.5.2 Dose Metrics Selected
The selection of the internal dose metric, used to establish "equivalent" exposures, is an important
decision in the use of the PBPK model for extrapolation of doses across routes and from rats to humans.
Internal dose metric selection is endpoint specific ( '006a). For example, the dose metric area-
under-the curve (AUC) of the average blood concentration is generally considered appropriate for
endpoints associated with repeat dose, assuming that a sustained internal dose of NMP is needed to
induce the effects. Endpoints that are associated with a single or short-term acute exposure, assuming
that a single dose effect is needed to induce these effects, are generally best evaluated by a metric that
captures peak exposure, such as C max.
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Reduced fertility following chronic exposure throughout several lifestages is best represented by the
AUC of average blood concentration. Similarly, as described above in Section 3.2.4.1, the endpoint of
decreased fetal body weight was presumed to be a marker of reduced fetal growth resulting from
repeated dose exposure during gestation. Therefore, decreased fetal body weight is expected to be better
represented by the AUC of average blood concentration during the vulnerable period of fetal
development.
EPA evaluated average AUC (total AUC divided by the number of days, staiti ng from the first day of
exposure until the day of measurement), e.g., GD6-20 for Becci et al., (! z,) or GD5-21 for Saillenfait
et al. (2003) with decreased fetal body weights for oral, inhalation and dermal routes of exposure to
confirm the metric is consistent in its estimation of a toxic response across routes. Seven studies that
measured fetal body weights were used for evaluating consistency between the internal dose and the
response expressed as percent change from control in body weight. The data points were fit to a line and
the correlation coefficient (R2) was used to evaluate linearity, shown in Figure 3-4 The Average Daily
AUC metric had a reasonable correlation with fetal body weight changes. Varying the period of
averaging for the daily AUC metric may provide higher correlations with fetal body weights
oral
Saillenfait et al., 2002
• Sitarek et al., 2012
inhalation
: Dupont, 1990
• Saillenfait et al., 2003
• Lee et al., 1987
• Hass et al., 1995
dermal
Becci et al., 1982
.BP
QJ
I 2
•***-
> c
~o o
U
E
o
o
GO
15
¦M
ro
c
4-1
W
o
CL
i-
o
15
4-»
0J
«D
Cto
c
ro
JZ
u
\p
10%
•
0%
§Jt
-10%
»•• •
•
-20%
-30%
-40%
-50%
-60%
y = -4E-05x
R2 = 0.787
0 2000 4000 6000 8000 10000
Average Daily AUC (hr mg/L)
Figure 3-4. Analysis of Fit: Average Daily AUC vs Fetal or Postnatal Body Weight
As described in Section 3.2.5.1, fetal resorptions and fetal mortality are assumed to be associated with
acute exposures during fetal development; however, lacking a clear understanding of the possible mode
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of action, the best dose metric for the evaluation of fetal resorptions and mortality is unclear. Per EPA
guidance (U.S. EPA. 2.006a). both AUC and peak blood dose (Cmax) were used to evaluate this endpoint.
Developmental effects such as fetal mortality and reduced fetal body weight occur following maternal
exposure. To identify Cmax or AUC for developmental effects, BMD modeling was based on internal
doses predicted by the PBPK model for adult females. Reproductive effects in the key study were
observed following exposure throughout gestation, lactation, puberty, and mating and it is unknown
which periods of exposure contributed to reduced fertility. Therefore, internal doses for fertility
endpoints were calculated based on internal exposure levels in young post-weaning rats, the life stage at
which calculated internal doses are the lowest. EPA performed a sensitivity analysis to determine the
effect of this assumption on the POD. BMDLs calculated based on lower i menial exposures in young
post-weaning rats were up to 2-fold lower than BMDLs calculated based on internal exposures at other
life stages.
3.2.5.3 Potentially Exposed and Susceptible Subpopulation
Based on the weight of the scientific evidence, reduced fertility and developmental toxicity are the most
sensitive effects of NMP exposure. The lifestages of greatest concern for developmental effects are
pregnant women, the developing fetus, and women of childbearinu age who may become pregnant.
Lifestages of concern for effects on reproducli\ e health and fertility include men and women of
reproductive age as well as children and adolescents. The results of one two-generation study in rats
(Exxon. 1991) indicate that developmental and early childhood exposure to NMP may contribute to risk
of reduced fertility in adulthood. Other potential hazards of NMP identified in Section 3.2.3 may be of
concern for other lifestages.
Certain human subpopulations may he more susceptible to exposure to NMP than others. One basis for
this concern is that the enzyme CYP2I-! 1 is partially involved in metabolism of NMP in humans and
there are large variations in CYI'21-1 expression and functionality in humans (Ligocka et al. 2003). The
variability in CYP2E1 in pregnant women could affect how much NMP reaches the fetus, which
typically does not express CYI'21 ¦ I ( ) Newborns and very young infants are particularly
susceptible to NMP exposure because they are metabolically immature. CYP2E1 is not fully expressed
in children until about ^"-days of age (.[¦- : ;;d et al.. 2003). The variability in CYP2E1 was identified
as an important uncertainly that was reflected in the calculation of the intraspecies uncertainty factor
(human variability) Pre-existing conditions affecting the liver may also impair metabolism of NMP in
some indi\ iduals I-'or example, latty liver disease has been associated with reduced CYP function
(Fisher et al )
Genetic variations or pre-existing conditions that increase susceptibility of the reproductive system, the
hepatic, renal, nervous, immune, and other systems targeted by NMP could also make some individuals
more susceptible to adverse health outcomes following consumer or workplace exposures. In addition,
people simultaneously exposed to other chemicals targeting these systems may also be more susceptible
to effects of NMP exposure.
While an uncertainty factor for interindividual variability provides some additional protection for
susceptible subpopulations, a lack of quantitative information on the extent to which any of these
specific factors increases risk precludes direct incorporation of these factors in the risk characterization.
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3.2.5.4 Derivation of Candidate Values
EPA evaluated data from studies described above (Section 3.2.5.1) to characterize NMP's dose-response
relationships and select studies to quantify risks for specific exposure scenarios.
In order to select the most appropriate key studies for this analysis, EPA considered the relative merits
of the oral, inhalation and dermal animal studies, with respect to: (1) the availability of primary data for
statistical analysis; (2) the robustness of the dose-response analysis; and (3) the exposure levels at which
adverse effects were observed.
The selected key studies provided the dose-response information for the selection of points of departure
(PODs). EPA defines a POD as the dose-response point that marks the beginning of a low-dose
extrapolation. This point can be the lower bound on the dose for an estimated incidence or a change in
response level from a dose-response model (i.e., benchmark dose or BMD), a \().\I-L or a lowest-
observed-adverse-effect level (LOAEL) for an observed incidence or change in le\ el of response. PODs
were adjusted as appropriate to conform to the exposure scenarios derived in Section 2 4
Studies Selectedfor BMD Modeling
Studies with only one exposure group (Hass et at.. 199f. were excluded in the
systematic review process because they provide limited information about the shape of the dose-
response curve and could not be used for BMD modeling. (jiven their concordance with other studies
that had multiple exposure groups they were slill seen as supportiv e of the dose-response relationship.
Studies that did not report a statistically significant effect for the endpoint being considered (Lee et at..
1987) may help with dose metric selection, but |iro\ ide only limited information about the shape of the
dose-response curve and were not included in the dose-response assessment of that endpoint.
For reduced fertility EPA selected the following study for dose response analysis:
• Exxon (.1.991): high quality oral dietary study
For reduced fetal body weights NW selected the following studies for dose-response analysis:
• Becci ( ); medium quality dermal study
• DuPont ( ); high quality inhalation study
• Saillenfait ( ) high quality oral gavage study
• Saillenfait ( ) high quality inhalation study
For fetal resorptions and increased fetal mortality EPA selected the following studies for dose-response
analysis:
• Becci ( ). medium quality dermal study
• Saillenfait ( ): high quality oral gavage study - combined with Saillenfait 2003 based on
internal do;>c
• Saillenfait (200:--) high quality inhalation study
• Sitarek et al. (2012): high quality oral gavage study
The Saillenfait et al. (2002) and Saillenfait et al. (2003) studies administered NMP via different routes
but were otherwise similar in study design, using the same exposure duration (GD 6-20) and the same
strain of rat (Sprague-Dawley); therefore these studies were combined based on PBPK-derived internal
dose metrics to provide additional statistical power for informing the dose-response curve.
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EPA guidance recommends a hierarchy of approaches for deriving PODs from data in laboratory
animals, with the preferred approach being physiologically-based pharmacokinetic modeling (U.S. EPA.
2.012a). When data were amenable, benchmark dose (BMD) modeling was used in conjunction with the
PBPK models to estimate PODs. For the studies for which BMD modeling was not possible (Sitarek et
at.. 2012; Becci et al. 1982). the NOAEL was used for the POD. Details regarding BMD modeling were
described in the supplemental file, Risk Evaluation for N-Methylpyrrolidone (NMP), Benchmark Dose
Modeling Supplemental File. Docket EPA-HQ-OPPT-2019-0236 (U.S. EPA. 2019D. Details regarding
the PBPK model can be found in Appendix I.
3.2.5.5 Derivation of Internal Doses
Peer-reviewed PBPK models for NMP in rats and humans (Appendix 1) facilitate cross-species
extrapolation of hazard information. In this risk evaluation. EPA uses the NMP PlJI'k models to
estimate internal doses (blood concentrations) that may occur in humans and compare these to PODs
based on internal doses associated with health hazards in nils The PBPK models allow N\\ lo evaluate
risks from aggregate exposures by calculating internal doses from combined inhalation and dermal
exposures. The models also reduce uncertainty in cross species extrapolation by incorporating
toxicokinetic information from rats and humans. To take ad\ anlage ol" these PBPK models, EPA
identified PODs in terms of internal doses in rats Internal doses are expected to have consistent effects
regardless of exposure route. EPA therefore used the PBPK model to deri\ e internal dose PODs based
on integrated toxicology data from studies using different exposure routes This section summarizes the
toxicokinetics of NMP, the PBPK models and dose metrics used to estimate internal doses in rats.
Toxicokinetic Parameters used in PHPK Modeling
NMP is well absorbed following inhalation, oral and dermal exposures (NMP Producers Group. 1995b).
In rats, NMP is distributed throughout the organism and eliminated mainly by hydroxylation to polar
compounds, which are excreted \ ia urine About So percent of the administered dose is excreted as NMP
and NMP metabolites within 24 hrs The major metabolite is 5-hydroxy-N-methyl-2-pyrrolidone (5-
HNMP). Studies in humans show that \IVIP is rapidly biotransformed by hydroxylation to 5-HNMP,
which is further oxidized to N-methyl- succinimide (MSI); this intermediate is further hydroxylated to 2-
hydroxy-N-methylsuccinimide (2-1 IMS I). The excreted amounts of NMP metabolites in the urine after
inhalation or oral intake represented about 100 and 65 percent of the administered doses, respectively
(Akessoi n. 1997).
Dermal absorption of \ \l P has been extensively studied as it typically poses the greatest potential for
human exposure Dermal penetration through human skin has been shown to be very rapid and the
absorption rate is in the range of 1-2 mg/cm2-hr. These values are 2- to 3-fold lower than those observed
in the rat. Prolonged exposures to neat NMP were shown to increase the permeability of the skin. Water
reduces the amount of dermal absorption (Pavan et al.. 2003) while other organic solvents (e.g., d-
limonene) can increase it (Huntingdon Life Sciences. 1998). The dermal penetration of 10 percent NMP
in water is 100-fold lower than that of neat NMP, while dilution of NMP with d-limonene can increase
the absorption of NMP by as much as 10-fold. The dermal absorption of neat NMP under different
occlusion conditions indicated that dermal absorption 1 hr post-exposure was greatest under un-occluded
conditions (69 percent), followed by semi-occluded (57 percent) and occluded (50 percent) conditions
(OECD. 2007b).
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Dermal uptake of vapor NMP has been reported in toxicokinetic studies in humans. Bader et al. (2008)
exposed volunteers for 8 hrs to 80 mg/m3 of NMP. Exposure was whole body or dermal-only (i.e., with
a respirator). Excretion of NMP and metabolites was used to estimate absorption under different
conditions. The authors found that dermal-only exposures resulted in the excretion of 71 mg NMP
equivalents whereas whole-body exposures in resting individuals resulted in the excretion of 169 mg
NMP equivalents. Under a moderate workload, the excretion increased to 238 mg NMP equivalents.
Thus, the authors estimated that the dermal absorption component of exposure from the air will be in the
range of 30 to 42 percent under whole-body exposure conditions to vapor.
Previously published PBPK models for NMP in rats and humans w civ adapted lor use by EPA (see
Appendix I and U.S. EPA (2015) for details of the PBPK model). The nil \ ersion of the model allows
for estimation of NMP time-courses in rat blood from inhalation, oral and dermal exposures. The human
version of the model, based on non-pregnant and pregnant women, also includes skin compartments for
portions of the skin in contact with NMP vapor and liquid and some of those details are described here
because it is an important component of human risk.
Analyzing the experimental studies of Akesson et al. (>K>+), the model yielded an a\ crime uptake of
2.1 mg/cm2-hr of neat NMP, but only 0.24 mg/cm2-hr of aqueous NMP (1:1 dilution in water).
Therefore, distinct values of the liquid permeability constant (I'VL), 2.05xl0"3 cm/h and 4.78xl0"4 cm/h,
were identified from the experimental data. The appropriate value of I'VL for neat vs. diluted NMP was
used in the respective exposure scenarios in this assessment. Absorption also depends on the partition
coefficient (PC) skin:liquid equilibrium, PSKL, which was taken to be the skin:saline PC reported by
Poet et al. (2010). PSKL = 0.42 [no units] and assumed not to \ aiy with dilution.
Predicted dermal uptake from liquid exposure is then a function of the liquid concentration, skin surface
exposed and duration of contact. The thickness of the liquid film does not factor directly into the
estimate. As a conservative estimate for user scenarios it is assumed that fresh material is constantly
depositing over the time of use such that the concentration on the skin remains essentially constant at the
formulation concentration. This is in contrast to simulations of experimental studies where the volume
placed on the skin at the start of the experiment is not replenished (Akesson et al.. 2004). in which case
the model tracks the amount ofWIP remaining in the film and hence the changing concentration for
absorption from diluted NMP
Penetration from vapor was estimated as part of model calibration using the Bader and van Thriel (2006)
inhalation data set. This report does not state how the subjects were dressed but the exposures were
conducted between late May and mid-June in Germany, so EPA assumed they wore short-sleeved shirts
and long pants. W hile there is no reason to expect that NMP vapors do not penetrate clothing, clothing
likely reduces uptake compared to open areas of skin. Since the fitted penetration constant (PV) is
multiplied by the skin surface area assumed to be exposed when calculating the penetration rate, these
cannot be uniquely determi ned from the toxicokinetic data. For the purpose of calibration and
subsequent modeling, it is assumed that the head, arms and hands are entirely exposed unless personal
protection equipment (PPE) is worn. Together the fractional skin area exposed to vapor (SAVC) is 25%
of the total skin surface area in the absence of PPE or liquid dermal contact.
The skin:air PC, PSKA, was calculated from the measured skin:saline and blood:saline PCs reported by
Poet et al. (2010) and the blood:air PC specified in their model code: PSKA = 44.5. With these values of
SAVC and PSKA, the average permeation constant for vapor-skin transport was estimated as PV = 16.4
cm/h. These assumptions and the value of PV resulted in a prediction of 20% of a total uptake from air
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(vapor) exposure via the dermal route. In contrast, Bader et al. (2008) measured 42% of total urinary
excretion occurring after only dermal exposure to vapors compared to combined inhalation and dermal
exposure under resting conditions. The discrepancy between the Bader et al. (2.008) data and the current
model predictions could be because the subjects in Bader and van Thriel (2006). on which this model is
based, wore long-sleeved shirts, thereby reducing dermal absorption or due to the use of an idealized
model of inhalation uptake which could over-predict uptake by that route.
For use scenarios in this assessment the air concentration in contact with the skin is assumed to be the
same as that available for inhalation with SAVC kept at 25% for consistency, except as specified in the
sections below when PPE is worn.
Rat Internal Doses for BMD
EPA used the validated PBPK models for extrapolating NMP doses across routes of exposure and from
animals to humans based on NMP-specific data (U.S. ES' .... ,. J. An internal dose metric such as a
measure of toxicant concentration in the blood is expected to be a better predictor of i espouse than the
applied dose (e.g., concentration in air) since it is closer to the site of the toxic effecl ( et al..
2012). Further, a good internal dose metric should correlate with or be predictive of toxicity irrespective
of the route of exposure by which it occurs. However, this is only true if the metric is in fact a measure
of the likelihood of a toxic response or intensity of a toxic effect.
For NMP the existing toxicity data identified the parent (NMP) rather than the metabolites 5-hydroxy-N-
methyl-2-pyrrolidone (5-HNMP), N-methy Isuccinimide (MSI) or 2-h\ dro.xv-N-methyl-succinimide (2-
HMSI) as the proximate toxicant (Saillenfait • ). Therefore, PBPK model-derived blood
concentrations of NMP were considered a better hasi s than applied dose for the dose-metric used in
extrapolation of health effects
3.2.5.6 J'oinls of Departure lor Human Health Hazard Endpoints
PODs for Acute Exposure
Acute exposure was defined lor workers as the exposure that occurs over the course of a single day. For
consumers, the acute exposure scenario was defined based on completion of a single project on a given
day. EPA selected increased resorptions (fetal mortality) as the most relevant endpoint for evaluating
risks associated with acute exposure to workers and consumers. Since repeated dose studies were used to
investigate this hazard endpoint and the mode of action for NMP is uncertain, EPA assessed dose-
response with both the internal dose metrics of Cmax and AUC.
The Saillenfait et (2002); Saillenfait et al. (2.003); Becci et al. ( 2); and Sitarek et al. ) studies
were selected for dose-response analysis. The Saillenfait et al. studies measured fetal resorptions and
were pooled across exposure routes. The Saillenfait et al. studies also used the same exposure duration
(GD 6-20) and the same strain of rat (Sprague-Dawley). Combining the data sets should provide
additional statistical power for identifying the BMDL and provide a more robust dose-response (low to
high). Moreover, the results for this endpoint were similar, via inhalation and oral exposure routes.
Therefore, the combined analysis was retained. A BMR of 1% for increased resorptions/fetal mortality
was used to address the relative severity of this endpoint ( 012a). Table 3-10 summarizes the
calculations leading to the determinations of a POD for each of the studies selected for dose-response
analysis.
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Table 3-10. Summary of Derivation of the PODs for Fetal Resorptions and Fetal Mortality
Kndpoint and
reference
(exposure
duralion/roiile)
Dose
Metric
Model11
liMR
mil)
Internal
dose
li.MDI,
Internal
dose
POD
Internal
dose
Kqiiivalent
administered
dose (route)"
Resorptions
(Saileenfair et al.
2003; Saillenfait et
al. 2002)d
(GD 6-20, oral and
inhalation)
Cmax
(mg/L
blood)
Hill
1%
RD
429
210
216
218 mg/kg
bw/day
(oral)
AUC (hr
mg/L
blood)
Power
1%
RD
3343
2128
2128
217 mg/kg
bw/day
(oral)
(Becci et al.. 1982)
(GD 6-15, dermal)
NOAEL 237 mu ku Inv/day
662
237 mg/kg
bw/day
(dermal)
612 mg/kg
bw/day
(oral)b
Fetal Mortality
(Sitarek et al..
201:)
(GD1-PND1, oral)
Cmax
(mu 1.)
No model
selected"
1%
RD
N/A
N/A
N/A
264 mg/kg
bw/day
(oral)
NOAEL = 450 mg/kg bw/day
265
RD = ivlnlivc deviation
Complete documentation of BMD modeling is available in Risk Evaluation for N-Methylpyrrolidone (NMP), Benchmark
Dose Madeline Supplemental File. Docket EPA-HO-OPPT-2019-0236 fU.S. EPA. 2019:0.
a Assuming daily oral gavage and initial BVV 0.259 kg (i.e. the same experimental conditions as the Saillenfait et al. (2002)
study) for the purposes of comparison across the studies.
b An oral dose of i > 12 ina'ka bw/day. given on GD 6-20, is predicted to yield the same peak concentration (662 mg/L).
0 BMD modeling failed In calculate an adequate BMD or BMDL value by either dose metric and BMD modeling results
are presented in the beiiclini;irk dose modeling supplemental file.
•'The combined models for the Saillenfait et al. (2003; 2002) studies do not meet the assumption of homogeneity of
variance as recommended for Benchmark Dose Modelins (U.S. EPA. 2012a). however the means are well-modeled; the
model with the lowest A1C was selected.
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EPA selected the combined analysis of the Saillenfait et al. (2002) oral study and the Saillenfait et al.
(2003) inhalation study for the derivation of the POD, 216 mg/L, to be used in the calculation of risk
estimates associated with acute exposure. The combination of the two Saillenfait et al. studies provides a
larger number of dose levels, hence further characterization of the dose-response curve. Moreover,
similar results for this endpoint were obtained in these studies which supports combining them.
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Additionally, the Saillenfait et al., studies were amenable to BMD modeling which also accounts for the
variability in the observed response. Neither the Becci study nor the Sitarek study were suitable for
BMD modeling, hence the NOAEL was used to derive a POD. Accordingly, EPA selected fetal
resorptions from the combined Saillenfait et al., studies for use as the basis for calculating risk for acute
NMP exposures.
The PODs based on internal dose (AUC and Cmax) were converted to an equivalent applied dose using
the PBPK model. The calculated equivalent administered doses are nearly the same as the NOAELs
identified in each study demonstrating consistency between the two methods lor deriving PODs.
EPA applied a composite uncertainty factor (UF) of 30 for acute exposure benchmark MOE, based on
the following considerations:
• An interspecies uncertainty/variability factor of 3 (UFa) was applied for uni mal-to-human
extrapolation to account for toxicodynamic differences between species. This uncertainty factor
is comprised of two separate areas of uncertainty to account for differences in the toxicokinetics
and toxicodynamics of animals and humans. In this assessment, the toxicokinetic uncertainty was
accounted for by the PBPK model as outlined in the RlX' methodology ( lb). As
the toxicokinetic differences are thus accounted for. only the toxicodynamic uncertainties
remain, and an UFa of 3 is retained to account for this uncertainty.
• A default intraspecies uncertainty/variability factor (UFuj of I" was applied to account for
variation in sensitivity within human populations The PBPK model did not account for human
toxicokinetic variability. Due to limited information on the degree that humans of varying
gender, age, health status, or genetic makeup might \ ary in the disposition of, or response to,
NMP a factor of 10 was applied.
PODs for Chronic Exposure
Chronic worker exposure was defined as exposure of 10% or more of a lifetime ( ).
Repeated exposures over the course of a work week are anticipated during chronic worker exposure. The
most sensitive endpoints were selected based on reproductive and developmental studies on NMP.
Adverse developmental outcomes from exposure during critical windows of development during
pregnancy can occur any time during the defined chronic worker exposure period. Reproductive toxicity
may be of concern for all workers of reproductive age. The in addition to the derivation of the point of
departure based on reproducti\ e and developmental toxicity considered repeated exposures, and the
POD is expected to be protecli\ e of pregnant women and children as well as men and women of
childbearing age
Decreased male fertility, decreased female fecundity and decreased fetal body weight were selected as
the endpoints of concern for chronic exposures. The (Exxon. 1991). Becci et al. (1982). (E I Dupont De
Nemours & Co. 199u;. .Jenfait et al. (2002). and Saillenfait et al. (2003) studies were selected for
dose-response analysis. The PBPK model and BMD modeling were applied to these studies to calculate
the BMDLs and PODs and BMD modeling results are described in Risk Evaluation for N-
Methylpyrrolidone (NMP), Benchmark Dose Modeling Supplemental File. Docket EPA-HQ-OPPT-
2019-0236 (U.S. EPA. 2019D. A benchmark response (BMR) of 10% for reduced fertility was used. A
BMR of 5% relative deviation for decreased fetal body weight was used because in the absence of
knowledge as to what level of response to consider adverse, it has been observed that 5% change relative
to the control mean is similar to statistically derived NOAELs in developmental studies (Kavlock et al..
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1995). The results are summarized in Table 3-11. It should be noted that the Saillenfait et al., studies
were analyzed both separately and combined. Also, the PBPK model was used to present the POD as the
equivalent applied oral dose, to allow for comparison.
Table 3-11. Summary of Derivation of the PODs for Reproductive and Developmental Effects
Endpoint and reference
(exposure
duration/route)
Mode!'
BMR
BMD
Internal
dose AUC
(hr mg/L
blood)
BIY1DL
internal
dose AUC
(hr mg/L
blood)
POD
Internal
dose AUC
(hr mg/L
blood)
Equivalent
applied oral
dose"
Fetal Body Weight
(Saillenfait etal 2003;
Saillenfait et al.. 2002)
(GD 6-20, oral and
inhalation)
Exponential
(M5)b
5%
RD
1937
1424
1424
152 mg/kg
bw/day
(Saillenfait et al.. 2002)
(GD 6-20 oral)
Exponential
(M5)
5%
RD
1637
1 184
1 184
129 mg/kg
bw/day
(Saillenfait et al.. 2003)
(GD 6-20 inhalation)
Linear
5%
RD
652
411
411
48 mg/kg bw/day
( >ont De Nemours
& Co. 1990)
(preconception exposure,
GD 1 -20, inhalation)
Exponential
(M2)
5%
RD
315
223
223
27 mg/kg bw/day
(Becci et al.. 1982)
(GD 6-15, dermal)
Polynomial
(3°)
5%
RD
5341
4018
4018
375 mg/kg
bw/day
Reduced Male Fertility
i:'?L) (Dietary
exposure throughout
gestation, lactation,
growth, pre-mating)
Log-
logistic
10%
ER
492cl
34 lc2
262cl
183c2
183
28 mg/kg bw/day
Reduced Female Fecundity
p 1 (Dietary
exposure throughout
gestation, lactation,
growth, pre-mating)
Log-
logistic
10%
ER
862cl
420c2
401cl
202cl
202
31 mg/kg bw/day
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BMD
BMDL
POD
Internal
Internal
Internal
Endpoint and reference
dose AUC
dose AUC
dose AUC
Equivalent
(exposure
(hr mg/L
(hr mg/L
(hr mg/L
applied oral
duration/route)
Model"
BMR
blood)
blood)
blood)
dose1'
RD = relative deviation; ER= extra risk
The POD selected for calculating risk of chronic NMP exposures is highlighted in bold. Complete documentation of BMD
modeling is available in Risk Evaluation for N-Methylpyrrolidone (NMP), Benchmark Dose Modeling Supplemental File.
Docket EPA-HQ-OPPT-2019-0236 (U.S. EPA. 2019:f).
a Assuming daily oral gavage CDs 6-20 and initial BVV 0.259 kg (i.e. the same experimental conditions as the Saillenfait et
al. (2002) study) for the purposes of comparison across the studies.
b The Saillenfait et al. (2003; 2002) studies do not meet the assumption of homogeneity of variance as recommended for
Benchmark Dose Modeling (U.S. EPA. 2012a). however the means are well-modeled. EPA evaluated the impact on the
BMDL of the smallest observed standard deviation for all dose levels, the largest standard deviation and the pooled
standard deviation. The BMDLs differed by less than 25% which provides assurance that the impact of the variances on
the BMDL was minimal.
0 In the Exxon (.1.99.1.) study, each dam had two sets of mating periods. Each mating period was analyzed separately. CI
indicates results for the first mating period and C2 indicates results from the second mating period. PODs for male
fertility and female fecundity in this study are calculated based on exposure levels in 50g rats immediately post-weaning.
EPA selected the POD derived from decreased male fertility (I S3 hr mg/L) in a two-generation
reproductive study (Exxon. 1991) to be used in the calculation of risk estimates associated with chronic
exposures. This high-quality study identified the most sensitive reproductive endpoints and had a
significant dose-response relationship that was adequately modeled by the BMD model. The POD for
effects on reduced female fecundity in this study was \ cry similar (202 hr mg/L) to the POD for effects
on male fertility, making it highly relevant to both male and female reproductive endpoints. This POD is
consistent with EPA's (iuidelines for Reproductive Toxicity Risk Assessment ( EPA. 1996)
The selected chronic POD is also protective of developmental toxicity endpoints of concern for pregnant
women, including reduced fetal body weight The PODs derived from effects on fetal body weight in
two developmental inhalation exposure studies t. ~; al. (2003" )upont De Nemours & Co.
1990) fall in an internal dose range (411 and 223 hr mg/ L), similar to the POD based on reduced
fertility, lending further support for the selected POD. Both inhalation studies used whole body
exposures where dermal absorption of NMP vapors likely contributed to the toxicity. This is similar to
human exposure scenarios, however, the unknown differences between human and rat dermal absorption
of NMP vapor adds uncertainty to values derived from either of these studies alone. While the POD for
the DuPont study was lower than the Saillenfait study, the dose-response relationship in the DuPont
study was not as robust as the Saillenfait study. Lower variability in body weights was observed in the
Saillenfait study than in the DuPont study, where statistically significant differences only occurred in the
lowest and highest dose groups, not the middle dose group.
The combination of the uantenfait et al. (2002) and Saillenfait et al. (2003) studies provided a more
extensive characterization of the dose-response curve across exposure routes. However, the Saillenfait et
al. (2003) study observed a statistically significant decrease in fetal body weights at an internal dose that
corresponds to an oral dose lower than the NOAEL in the Saillenfait et al (2002) oral study. This
implies that fetal body weights were more sensitive to inhalation exposures and this was not fully
accounted for in the PBPK model. Therefore, the combined analysis was not retained.
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There are limitations to the Becci study: the duration of dosing was shorter than for the Saillenfait
studies and it resulted in a higher POD. The uncertainty regarding exposure duration and sampling time
leads to uncertainty about recovery and compensation. Therefore, this study was not selected for the
POD.
The PODs based on internal dose (AUC) were converted to an equivalent applied dose using the PBPK
model. The calculated equivalent administered doses are nearly the same as the NOAELs identified in
each study (where available) demonstrating consistency between the two methods for deriving PODs.
EPA applied a composite uncertainty factor (UF) of 30 for chronic exposure benchmark MOE, based on
the following considerations:
• An interspecies uncertainty/variability factor of 3 (UFa) was applied for animal-to-human
extrapolation to account for toxicodynamic differences between species. This uncertainty factor
is comprised of two separate areas of uncertainty lo account for differences in the toxicokinetics
and toxicodynamics of animals and humans. In this assessment, the toxicokinelic uncertainty was
accounted for by the PBPK model as outlined in llic RfC methodology ( 1)). As
the toxicokinetic differences are thus accounted lor. only the toxicodynamic uncertainties
remain, and an UFa of 3 is retained to account for this uncertainty.
• A default intraspecies uncertainty/variability factor (I T'n) of I n was applied to account for
variation in sensitivity within human populations. The PBIMs. model did not account for human
toxicokinetic variability. Due to limited information on the degree of humans of varying gender,
age, health status, or genetic makeup might \ arv in the disposition of, or response to, NMP a
factor of 10 was applied.
3.2.6 Summary of Human Health Hazards
Table 3-12 summarizes the hazard studies, health endpoints and UFs that are considered relevant for this
risk evaluation. The reported PODs relied internal dose estimates (blood concentrations) for comparison
with internal dose estimates of human exposures from multiple routes (e.g., inhalation and/or dermal).
Table 3-12. PODs Selected lor Non-Cancer K fleets from NMP Exposures
Kxposure
Diii'iilion
Target
System
Species
Dose
Metric
UMR
POD
I! ITcd
I ncerlainty
I'actorsd I s)
for Benchmark
moi:
References
Data
Quality
Score
Acute
Developmental
Rat
Cmax
(mg/L)
1%
RD
216
Ivlal
Resorptions
and Fetal
Mortality
I 1 3
UFh = 10
Total UF = 30
(
sanienrait
et al.„
2002)
High
Chronic
Reproductive
Rat
AUC
(hr-
mg/L)
10%
ER
183
Decreased
Male
Fertility
UFa = 3
UFh = 10
Total UF = 30
(Exxon.
)
High
RD = relative deviation; ER= extra risk; UFa = interspecies UF; UFh = intraspecies UF (IIS. EPA, 2002).
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Primary Strengths
There is a robust dataset for the critical reproductive and developmental effects that serve as the basis
for the PODs used in this risk characterization. The available studies demonstrate clear, consistent
effects on a continuum of reproductive and developmental endpoints following NMP exposure across
oral, inhalation, and dermal exposure routes. Each of the critical endpoints supporting the PODs
represents an adverse effect that is biologically relevant to humans. The acute POD based on fetal
mortality reflects consistent observations across multiple high-quality studies using multiple exposure
routes. The chronic POD selected based on reduced fertility following exposure across lifestages in a
high-quality study is supported by other high-quality studies demonstrating reduced fertility in males
and females exposed only as adults. The POD derived from reduced fertility is within close range of
PODs derived from a developmental endpoint (fetal body weight) that is consistently observed across
studies, species, and routes of exposure. The quality of the studies, consistency of effects, relevance of
effects for human health, coherence of the spectrum of reproductive and developmental effects observed
and biological plausibility of the observed effects of NMP contribute to the overall confidence in the
PODs identified based on reproductive and developmental endpoints.
The NMP PBPK models allow EPA to identify points of departure based on blood concentrations of
NMP that are associated with effects in animal models. Because the effects of NMP at a specific blood
concentration are independent of exposure route, a single internal dose POD can be applied to evaluate
risk from all routes of exposure. This eliminates the need for extrapolating hazard information across
exposure routes. The PBPK model also accounts for toxicokinetic information in rats and humans,
reducing a source of uncertainty associated with cross-species extrapolation
Primary Limitations
While there is a large amount of animal data on reprodncti\ e and developmental effects of NMP, there
are not studies on reproductive and developmental toxicity of NMP in humans. Therefore, this risk
evaluation relies on the assumption that reproductive and developmental toxicity observed in animal
models is relevant to human health It is unknown whether this assumption leads to an underestimate or
overestimate of risk.
Some potentially sensitive endpoints remain poorly characterized. For example, neurodevelopmental
effects were observed in response to a high dose exposure, but no NOAEL has been established for these
effects. Tf endpoints that are not well characterized are in fact more sensitive to NMP than the endpoints
that ser\ e as the basis for the POD. this could lead to an underestimation of risk.
There are some uncertainties associated with the specific endpoint used as the basis for the chronic
POD. There are a limited set of studies available to EPA on the specific endpoint used as the basis for
the POD. The chronic POD is based on sensitive reproductive endpoints observed in a 2-generation
reproductive study Two of the subsequent studies that evaluated fertility in 2-generation reproductive
studies were not fully a\ ailable to EPA for review. A third 2-generation study via inhalation exposure
was available but deviated substantially from EPA and OECD guidelines and had serious limitations due
to uncertainties about the actual doses achieved, making it difficult to draw clear conclusions from the
results. Although the critical effect is only observed in a single study, it is supported by evidence in
other high-quality studies of reduced fertility in male and female rats exposed as adults. It is unclear
whether this data limitation leads to an overestimate or underestimate of risk.
In addition, because exposure in the key study occurred throughout gestation, lactation, post-weaning,
puberty and pre-mating, it is not possible to determine which exposure periods contributed to reduced
fertility. EPA therefore established a POD based on lifestage at which the lowest level of exposure
relative to body weight occurred. This assumption could contribute to an overestimate of risk.
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There is some uncertainty around the techniques used to generate NMP air concentrations for animal
exposures in some supporting studies considered in the weight of evidence. Experimental conditions
may have inadvertently resulted in the inclusion of aerosolized particles in the exposure chamber in
some inhalation exposure studies. NMP is hygroscopic; therefore, variations in temperature, humidity
and/or test protocol (e.g., the number of air changes, use of a spray or nebulization technique to generate
test atmospheres) may impact the NMP air saturation concentration, resulting in condensation of NMP.
Aerosol formation would result in increased dermal and/or oral exposures (from grooming behavior) in
addition to the intended inhalation exposure. For example, the 2-generation inhalation study (Solomon et
aL !1,< \ ^ I * Hipomt De Nemours & Co. 1990) noted that condensation observed on the chamber walls
at the highest dose indicates that the actual air concentrations of NMP were lower than the intended
exposure. Nonetheless, higher test concentrations and total body exposures lo YMP were associated
with adverse developmental effects in rats.
Overall Confidence
EPA has high confidence in the acute and chronic PODs identified for evaluating risk from NMP. The
PODs are derived from endpoints that fall along a continuum of reproductive and de\ clopmcntal effects
that are consistently observed in response to NMP across oral, dermal and inhalation exposure routes.
Application of the PBPK model reduces uncertainties associated with extrapolation across species and
exposure routes, further contributing to overall confidence in the PODs.
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4 RISK CHARACTERIZATION
4.1 Environmental Risk
4.1.1 Risk Estimation Approach
The environmental risk of NMP is characterized by calculating risk quotients or RQs (
Bamthouse et at.. 1982). The RQ is defined as:
RQ = Environmental Concentration I ¦fleet Le\ el
An RQ equal to 1 indicates that the exposures are the same as the concentration that causes effects. If the
RQ is above 1, the exposure is greater than the effect concentration. Tf the RQ is below 1, the exposure
is less than the effect concentration. The Effect Levels or Concentrations of Concern (COCs) used to
calculated RQs are identified in Section 3.1.2 and are shown in Table 4-1.
Table 4-1. Concentrations of Concern (COCs) for Environmental Toxicity
Km i roil in on t ;< 1 Toxicity
Most Sensiti\e Species
Concent ration of Concern (COC)
Aculc To\icil\ , aquatic organisms
48-llour aquatic in\cilchalcs
1 <><>.( (ig/L
Chronic Toxicity, aquatic organisms
21-Day aqualic invcrlclnalcs
1.770 iig/L
EPA used estimated acute and chronic exposure concentrations of NMP in surface water (Section 2.3.2)
and acute and chronic concentrations of concern (COCs) (Section 3.1.2) to evaluate the risk of NMP to
aquatic species using Tabic 4-2 summarizes the risk quotients (RQs) for the acute and chronic risk of
NMP. The RQ values for acute and chronic risks are 0.0022 and 0.85, respectively. Based on these
values risks are not indicated for either acute or chronic exposure pathways As pre\ iously stated, an RQ
below I indicates that the exposure concentrations of WIP is less than the concentrations that would
cause an effect to organisms in the aquatic exposure pathways
Table 4-2. Calculated Risk Quotients (UQs) for NMP
.Maximum Kxposurc
Concentrations of
Concentration
Concern (COC)
RQ
Acute Risk
224 |ig/L
100,000 |ig/L
0.0022
Scenario
Chronic Risk
1,496 |ig/L
1,770 ,ig/L
0.85
Scenario
Based on the calculated RQs for acute and chronic risk scenarios, EPA concludes that NMP
demonstrates a low hazard to environmental receptors. Based on the RQ values, EPA also concludes that
NMP does not present unreasonable risks to the environment.
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4.1.2 Assumptions and Key Uncertainties for the Environment
In the NMP Problem Formulation ( ;) and this RE, EPA completed a screening level
evaluation of environmental risk using inherently conservative assumptions. The analysis was completed
using "high-end" estimated concentrations of NMP in the aquatic environment as described in Section
2.3.2 and compared those acute and chronic exposure estimates to conservative measures of acute and
chronic hazard (concentrations of concern) as described in Section 3.1.2. EPA in the NMP Problem
Formulation ( )18c) did not conduct any further analyses on pathways of exposure for
terrestrial receptors as described in Section 2.5.3.1 of the NMP Problem I'oiniulation and further
described in Section 2.2 and 2.3 of this RE.
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4.2 Human Health Risk
The human health risks associated with NMP conditions of use identified in Section 1.4 are discussed
below. Specific information regarding the methodologies used to derive exposure estimates, including
related assumptions and data limitations or uncertainties can be found in Section 2.4; an overview of the
potential human health hazards, including key and supporting studies is presented in Section 3.2.
4.2.1 Risk Estimation Approach
Acute or chronic MOEs were used in this assessment to estimate non-cancer risks using Equation 4-1.
EPA calculated MOEs and compared them to the benchmark MOE to i nterpret the MOE risk estimates
for each exposure scenario. The MOE estimate was interpreted to have iicgligiMe human health risk if the
MOE estimate was greater than the benchmark MOE (i.e., the total UF). Typically, the larger the MOE,
the more unlikely it is that a non-cancer adverse effect would occur.
Equation 4-1. Equation to Calculate Non-Cancer Kisks l-ollowing Acute or Chronic Exposures
Using Margin of Exposures
Non — cancer Hazard value (POD)
M0E= Human Exposure
Where:
MOE = Margin of exposure (unit I ess)
(POD) = internal dose (('mux. mg, L or \l (' hr mg/L)
Human Exposure imenial dose exposure estimate
(Cmax, mg/L or AUC hr mu I.) from occupational or consumer
exposure assessment. Cmax was used for acute exposure scenarios
and the \l C was used for chronic exposure scenarios.
In this risk characterization. peer-i e\ iewed PBPK models for NMP in rats and humans (Appendix I)
allow EPA to estimate internal doses (Mood concentrations) that may occur in humans and compare
these to PODs based on internal doses associated with health hazards in rats. MOEs are calculated by
dividing PODs in units of internal blood concentrations in rats by human blood concentrations expected
for specific exposure scenarios For characterization of acute risks, PODs and human exposure estimates
are in terms of maximum Mood concentrations (Cmax) while for chronic risks, they are in terms of total
daily exposure (AUC).
The PBPK models facilitate integration of exposure and hazard information across exposure routes. For
each exposure scenario, the PBPK model is used to aggregate simultaneous inhalation and dermal
exposures into a single human internal dose. The relative contribution of inhalation and dermal exposure
routes varies across exposure scenario. The PBPK models also allow the risk characterization to
incorporate information about toxicokinetics. Internal doses predicted by the model account for internal
exposure that remains after external exposure has ceased, reflecting the rate of metabolism and
elimination. Toxicokinetic information captured in rat and human models reduces toxicokinetic
uncertainty associated with interspecies extrapolation.
Table 4-3 and Table 4-4 summarize the use scenarios, populations of interest and toxicological
endpoints used to evaluate risk for acute and chronic exposures for workers and acute exposure for
consumers, respectively.
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5104 Table 4-3. Use Scenarios, Populations of Interest and Toxicological Endpoints for Assessing
Occupational Risks Fo
lowing Acute and Chronic Exposures to NMP
Populations and
Toxicological
Approach
Occupational I so Scenarios of NMP
Population of Interest
and Exposure
Scenario:
Users:
Adults and youth of both sexes (>16 years old) exposed In NMP during product use in
a workday, typically 8 or 12 hours.1'2
Occupational Non-users:
Adults and youth of both sexes (>16 years old) iikIiivciK exposed to NMP while in the
vicinity of product use.
Health Effects of
Concern,
Concentration and
Time Duration
Acute Non-Cancer Health Effects:
Developmental toxicity (fetal
mortality).
Hazard Values (POD): 216 mg/L
(Cmax)
Chronic Non-C inn er Health Effects:
Reproductive toxicm (reduced fertility)
Hazard Values (POD): 1X3 hr-niu 1,
(AUC)
Uncertainty Factors
(UF) used in Non-
Cancer
Margin of Exposure
(MOE) calculations
UFs for Acute 1 la/.ard
Total UF = 30 (10X I l: * v\ III)
UFs for Chronic Hazard:
Total I l: = 30 (10X UFH * 3X UHA)3
Notes:
1 It is assumed that there is no suhsianiial buildup of \\ll' mi ihe hody between exposure events due to NMP's short
biological half-life (-2 5 Iiim
2 EPA expects that the users of Wll'-hased products and exposed lion-users are generally adults, but younger individuals
may be users and exposed iiou-uscis
5 UFH=intraspecies UF; UFA= inierspeeies I I '
5106
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Table 4-4. Use Scenarios, Populations of Interest and Toxicological Endpoints for Assessing
Consumer Risks Following Acute Exposures to NMP
Populations and Toxicological
Approach
Consumer I 'so Scenarios of NMP
Population of Interest and
Exposure Scenario:
Users:
Adults of both sexes (>16 years old) typically exposed to NMP1'2
Bystanders:
Individuals of any age indirectly exposed to NMP while being in the rest
of the house during product use see Section 2 4 2 for more information.
Health Effects of Concern,
Concentration and Time
Duration
Non-Cancer Health Effects:
Developmental toxicity (fetal mortality).
Hazard Values (POD): 21 (•> mu 1. (Cmax)
Uncertainty Factors (UF) used
in Non-Cancer
Margin of Exposure (MOE)
calculations
Total I T 3d (1 OX UFn * 3X I'lliV
1 It is assumed that there is no substantial buildup of WIP in ihe hod\ helueeu exposure events due to NMP's short
biological half-life (~2.5 hrs).
2 EPA expects that the users of ihese products are generalk adulis. hm younger individuals may be users of NMP-based paint
strippers.
3 UFH=intraspecies UF. 1 l'\ interspecies 1 !¦'
4.2.2 Risk Estimation for Kxposures for Occupational Use of NMP
The risk characterization was performed using internal dose estimates derived from PBPK modeling of
occupational exposures based on available monitoring data. The following sections present the results of
the PBPK modeling results lor risk estimation of acute and chronic inhalation and dermal exposures
following occupational use of NMP in each condition of use. MOE values that are bold are below the
benchmark MOh of 30 (described in Section 3.2.5.6).
For each occupational exposure scenario, EPA predicted the likelihood of glove use based on the
characteristics described in Table 2-3. For scenarios that have only industrial sites, EPA assumes that
SDS recommendations are followed and that workers are likely to wear protective gloves and have
specialized training on the proper usage of these gloves, corresponding to a protection factor of 20. In
scenarios that cover a variety of commercial and industrial sites, EPA assumes that either no gloves are
used or if gloves are used, that occlusion may occur for some high-end exposure scenarios,
corresponding to a protection factor of 1. If occlusion were to occur, contact duration would be
extended. Based on the widespread use of NMP in these occupational scenarios, EPA assesses a central
tendency scenario assuming the use of gloves with minimal to no employee training, corresponding to a
protection factor of 5. For the Recycling and Disposal scenarios, EPA assesses both high-end and central
tendency scenarios assuming the use of gloves with basic employee training, corresponding to a
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protection factor of 10. As indicated in Table 2-3, use of protection factors above 1 is valid only for
glove materials that have been tested for permeation against the NMP-containing liquids associated with
the condition of use.
For high-end scenarios where glove use without occlusion was assumed and MOEs were above the
benchmark MOE, EPA conducted additional modeling of exposures for no glove use to determine
whether lack of glove use could result in MOEs below the benchmark MOE. For high-end scenarios
where no glove use was assumed and MOEs were below the benchmark MOE, EPA conducted
additional modeling of exposures for glove use to determine whether ulo\ c use could result in MOEs
above the benchmark MOE.
More information on glove materials for protection against NMP is in Appendix I .
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Manufacturing of NMP
Table 4-5. Non-Cancer Risk Estimates for Acute Exposures Following Occupational Use of NMP
in Manufacturing a
1 lealtli Effect,
End point itiul Study
Acute
POD.
('max
(m»/l.
)
Exposur
e l.e\el
Acute Exposure, Peak
blood con ceil t rat ion
moi:
ISencli in a r
k moi:
(= Total
1 1 )
No
»lo\e
s
(Jo\e
s PI
It)
(Jo\e
s PI
20
No
»lo\e
s
(Jo\e
s PI
It)
(Jo\e
s PI
20
DEVELOPMENTA
L EFFECTS
Increased Fetal
Resorptions
(2003; Saillenfait et
al.„ 2002)
216
Central
Tendenc
V
4.2
0.42
0.21
52
5 IS
11)25
30
High-
End
21.9
: 14
1.11
9.9
101
h>4
a MOEs < 30 are indicated in bold
b Central tendency means: typical air concentration, 1-hand dermal (445 cm surface area exposed), and central tendency
NMP weight fraction (EPA expects 100% NMP for this condition of use). 1 hull-end means worst-case air concentration, 2-
hand dermal (890 cm2 surface area exposed), and hi all-end weight NMP fraction (1 iP A expects workers use 100% NMP for
this condition of use).
MOEs calculated using central tendency estimates lor acute exposure to workers during bulk container
unloading are above the benchmark MOE (30) in the absence of glove use. One MOE calculated using a
high-end estimate for acute exposure to workers during drum unloading is below the benchmark MOE
in the absence of glo\ e use. the MOI! calculated using a glove protection factor (PF 10) is above the
benchmark MOE.
Table 4-6. Non-Cancer Uisk Kslimales for Chronic Kxposures Following Occupational Use of
NMP in Manufacturing •'
Clironi
c POD.
Chronic Exposure,
Al C (lir m»/E)
moi:
lien cli mar
Health Effect,
Al C
No
(Jo\e
Clo\e
No
Clo\e
(Ihnc
k moi:
End point and
(In
Exposur
«ilo\e
s PI
s PI
«ilo\e
s PI
s l»l
(= Total
Studv
in «•/!.)
e l.e\el
s
10
20
s
10
20
1 1 )
REPkODl CTIY
EEl l EC I S
Decreased
183
Central
Tendency
8.6
0.86
0.43
21
213
423
30
Fertility
(Exxon. 1991)
High-End
81.4
7.4
3.82
2.2
25
48
a MOEs < 30 are indicated in bold
b Central tendency means: typical air concentration, 1-hand dermal (445 cm2 surface area exposed), and central tendency
NMP weight fraction (EPA expects 100% NMP for this condition of use). High-end means worst-case air concentration,
2-hand dermal (890 cm2 surface area exposed), and high-end weight NMP fraction (EPA expects 100% NMP for this
condition of use).
MOEs calculated for manufacturing using central tendency and high-end estimates of chronic exposure
to workers are below the benchmark MOE (30) in the absence of glove use and above the benchmark
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MOE with the incorporation of glove protection factors (PF 10 and PF 20 for central tendency and high-
end estimates, respectively).
EPA considered the assessment approach, the quality of the data, and uncertainties to determine the
level of confidence.
Primary Strengths
EPA assessed dermal exposure to liquids using the most recent CDR data for concentration provided by
industry submitters. Modeling, in the middle of the approach hierarchy, was used to estimate
occupational air concentrations for both the loading of NMP into bulk containers and into drums. For
modeling of these air concentrations, EPA attempted to address variability in input parameters by
estimating both central tendency and high-end parameter values. Additionally, lor modeling of air
concentrations during the loading of drums, EPA used Monte Carlo simulation lo capture variability in
input parameters. EPA expects the duration of inhalation and dermal exposure to be realistic for loading
activities, as these durations are based on the length of lime required to load NMP into specific container
sizes (i.e., tank trucks, rail cars, and drums).
Primary Limitations
The representativeness of the estimates of duration of inhalation unci dermal exposure for the loading
activities toward the true distribution of durations for all worker acti\ ities in this occupational exposure
scenario is uncertain. NMP concentration is reported to CDR as a range and EPA assessed only the
upper end of the range since a central value cannot he ascertained for this scenario. Skin surface areas
for actual dermal contact are uncertain. EPA did not find data on the use of gloves for this occupational
exposure scenario and assumed glove usage is likely based on judgment. The assumed glove protection
factor values are highly uncertain. EPA is uncertain of the accuracy of emission factors used to estimate
fugitive NMP emissions and thereby model NMP air concentrations. The representativeness of the
modeling results toward the true di stribution of inhalation concentrations for this occupational exposure
scenario is uncertain.
Overall Confidence
Considering the overall strengths and limitations, the overall confidence of the PBPK input parameters
for this occupational exposure scenario is medium. The studies that support the health concerns for
adverse de\ elopmental effects following acute exposure and adverse reproductive effects following
chronic exposure are described above in Section 3.2. Overall, EPA has high confidence in the health
endpoints and PODs selected for acute and chronic risk characterization. Section 3.2.6 describes the
justification for this confidence rating.
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4.2.2.2 Repackaging
Table 4-7. Non-Cancer Risk Estimates for Acute Exposures Following Occupational Use of NMP
Acute Kxposure, Peak
moi:
Acute
blood concent
ration
POD.
(mg/l.)
lien chin a r
('max
No
(llo\e
(llo\e
No
(llo\e
(llo\e
k moi:
1 lealtli KITccl,
(m»/l.
Kxposur
»lo\e
s PI
s PI
»lo\ e
s PI
s PI
(= Total
Kndpoint iincl Study
)
e l.e\el
s
It)
20
s
It)
20
1 1 )
DEVELOPMENTA
Central
L EFFECTS
Tendenc
4.2
0.42
0.21
52
5 IS
1025
Increased Fetal
216
y
30
Resorptions
High-
End
(2003; Saillenfait et
aL 2002)
21.9
2.14
1.11
9.9
101
h>4
a MOEs < 30 are indicated in bold
b Central tendency means: typical air concentration, 1-hand dermal (445 cm sin face area exposed), and central tendency
NMP weight fraction (EPA expects 100% NMP for this conditio] i of use) 11 mh-eiid means worst-case air concentration,
2-hand dermal (890 cm2 surface area exposed), and high-end weiuhl
\\1l' fraction (EPA expects 100% NMP for this
condition of use).
MOEs calculated for importation and repackaging using central tendency estimates of acute exposure to
NMP are above the benchmark MOE (30) in the absence of glove use. One MOE calculated using a
high-end estimate for acute exposure (without gloves) is below the benchmark MOE; the MOE
calculation incorporating a glo\ c prolcction factor (PF 10) is abo\ c the benchmark MOE.
Table 4-8. Non-Cancer Risk Kslimates for Chronic Kxposures Following Occupational Use of
NMP in Importation and Repackaging a
Health KITect.
Kndpoint and
Study
Clironi
c POD.
Al C
(In
m»/L)
Kxposur
e I.cm'I h
Chronic Kxposure,
Al C (lir ni»/l.)
moi:
lien cli mar
k moi:
(= Total
I T)
No
«ilo\e
s
(Jo\e
s PI
10
Clo\e
s PI
20
No
«ilo\e
s
Chnc
s PI
10
(Ihnc
s PI
20
RKPkODl CTIY
i: Kl 1 IX I S
Decreased
Fertility
(EXXOII. lyy. )
183
Central
Tendency
8.6
0.86
0.43
21
213
423
30
Ihdi-I'nd
81.4
7.4
3.82
2.2
25
48
a MOEs < 30 are indicated in hold
b Central tendency means i\ pical air concentration, 1-hand dermal (445 cm2 surface area exposed), and central tendency
NMP weight fraction (EPA expects 100% NMP for this condition of use). High-end means worst-case air concentration,
2-hand dermal (890 cm2 surface area exposed), and high-end weight NMP fraction (EPA expects 100% NMP for this
condition of use).
MOEs calculated for importation and repackaging using central tendency and high-end estimates of
chronic exposure to workers are below the benchmark MOE (30) in the absence of glove use; central
tendency estimates are above the benchmark MOE with gloves (PF 10). One MOE calculated using a
high-end estimate for chronic exposure to workers with gloves (PF 10) is below the benchmark MOE
Page 217 of 487
-------
5212
5213
5214
5215
5216
5217
5218
5219
5220
5221
5222
5223
5224
5225
5226
5227
5228
5229
5230
5231
5232
5233
5234
5235
5236
5237
5238
5239
5240
5241
5242
5243
5244
5245
5246
5247
5248
5249
5250
5251
PEER REVIEW DRAFT, DO NOT CITE OR QUOTE
Although the MOE calculation incorporating a glove protection factor (PF 20) is above the benchmark
MOE, EPA has not found information that would indicate specific activity training (e.g., procedure for
glove removal and disposal) for tasks where dermal exposure can be expected to occur in industrial
OES. The PF 20 glove protection factor is not assumed for any central tendency or high-end exposure
estimates.
EPA considered the assessment approach, the quality of the data, and uncertainties to determine the
level of confidence.
Primary Strengths
EPA assessed dermal exposure to liquids using the most recent CDR data lor concentration provided by
industry submitters. Modeling, in the middle of the approach hierarchy, was used to estimate
occupational inhalation exposure concentrations for both the unloading of NMP lYom bulk containers
and from drums. For modeling of these air concentrations. F.PA attempted to address \ ari ability in input
parameters by estimating both central tendency and high-end parameter values. Additionally, for
modeling of air concentrations during the loading of drums. F.P A used Monte Carlo simulation to
capture variability in input parameters. EPA expects the duration of inhalation and dermal exposure to
be realistic, as the durations are based on the length of time to load WIP into specific container sizes
(i.e., tank trucks, rail cars, and drums).
Primary Limitations
The representativeness of the estimates of duration of inhalation and dermal exposure for the unloading
activities toward the true distribution of duration for all worker activities in this occupational exposure
scenario is uncertain. NMP concentration is reported to CDR as a range and EPA assessed only the
upper end of the range since a central value cannot be ascertained for this scenario. Skin surface areas
for actual dermal contact are uncertain. EPA did not find data on the use of gloves for this occupational
exposure scenario and assumed glove usage is likely based on judgment. The assumed glove protection
factor values are highly uncertain. EPA is uncertain of the accuracy of the emission factors used to
estimate fugitive NMP emissions and therein to model NMP air concentrations. The representativeness
of the modeling results toward the true distribution of inhalation concentrations for this occupational
exposure scenario is uncertain
Overall ('onfidence
Considering the overall strengths and limitations, the overall confidence of the PBPK input parameters
for this occupational exposure scenario is medium. The studies that support the health concerns for
adverse developmental effects following acute exposure and adverse reproductive effects following
chronic exposure are described above in Section 3.2. Overall, EPA has high confidence in the health
endpoints and PODs selected for acute and chronic risk characterization. Section 3.2.6 describes the
justification for this confidence rating.
Page 218 of 487
-------
5252
5253
5254
5255
5256
5257
5258
5259
5260
5261
5262
5263
5264
5265
5266
5267
4.2.2.3
PEER REVIEW DRAFT, DO NOT CITE OR QUOTE
Chemical Processing, Excluding Formulation
Table 4-9. Non-Cancer Risk Estimates for Acute Exposures Following Occupational Use of NMP
in Chemical Processing (Excluding Formulation)3
Acute Kxposure, Peak
moi:
Acute
blood concent
ration
POD.
(mg/l.)
lien chin a r
(max
No
(Jo\e
(Jo\e
No
(;io\c
(Jo\e
k moi:
1 lealtli K ITec I,
(m»/l.
Kxposu i'
»lo\e
s PI
s PI
»lo\ e
s l»l
s PI
(= Total
Kndpoint and Study
)
e I.cm'I ¦'
s
It)
20
s
itt
20
1 1 )
DEVELOPMENTA
Central
L EFFECTS
Tendenc
3.5
0.35
0.IS
1198
Increased Fetal
216
V
30
Resorptions
(2003; Saillenfait et
al. 2002)
High-
End
7.0
0.72
0.37
30.8
301
579
a MOEs < 30 are indicated in bold
b Central tendency means: typical air concentration, 1-hand dermal (445 cm sin face area exposed), and central tendency
NMP weight fraction (EPA expects 100% NMP for this condition of use) 11 mh-end means worst-case air concentration,
2-hand dermal (890 cm2 surface area exposed), and high-end weight N MP I nchon < EPA expects 100% NMP for this
condition of use).
MOEs calculated for chemical processing (excluding formulation) using central tendency and high-end
estimates of acute exposure to NMP are abo\ c the benchmark MOI- (30) in the absence of glove use.
Table 4-10. Non-Cancer Risk Estimates for Chronic Exposures hollowing Occupational Use of
NMP in Chemical
'rocessing (Kxcluding Formulation) a
(lironi
C hroilic Kxposui'e,
moi:
c POD.
Alt' (lir ni»/l.)
lien cli mar
Health K fleet.
Al (
No
(Ihnc
(llo\e
No
(Ihnc
(Ihnc
k moi:
Kiul point and
(lir
Kxposui'
»lo\e
s PI
s PI
»lo\e
s PI
s PI
(= Total
Studv
m»/l.)
e l.e\el h
s
It)
20
s
10
20
I T)
RKPkODl (TIN
i: i:i i i:c is
Decreased
IN i
( cniral
Iciidcncs
6.2
0.63
0.32
29
291
570
30
Fertility
(Exxcii. )
High-End
12.7
1.3
0.67
14
143
275
aMOEs < 30 are mdic;
ilcd in bold
b Central tendency means ivpical air concentration, 1-hand dermal (445 cm2 surface area exposed), and central tendency
NMP weight fraction < 1P \ expects 100% NMP for this condition of use). High-end means worst-case air concentration,
2-hand dermal (890 cm surface area exposed), and high-end weight NMP fraction (EPA expects 100% NMP for this
condition of use).
MOEs calculated for chemical processing (excluding formulation) using central tendency and high-end
estimates of chronic exposure to NMP are below the benchmark MOE (30) in the absence of glove use.
MOEs calculated for chemical processing (excluding formulation) using central tendency and high-end
estimates of chronic exposure to NMP are above the benchmark MOE (30) with incorporation of a glove
protection factor (PF 10).
Page 219 of 487
-------
5268
5269
5270
5271
5272
5273
5274
5275
5276
5277
5278
5279
5280
5281
5282
5283
5284
5285
5286
5287
5288
5289
5290
5291
5292
5293
5294
5295
5296
5297
5298
5299
5300
PEER REVIEW DRAFT, DO NOT CITE OR QUOTE
EPA considered the assessment approach, the quality of the data, and uncertainties to determine the
level of confidence.
Primary Strengths
EPA assessed dermal exposure to liquids using the most recent CDR data for concentration provided by
industry submitters. Modeling, in the middle of the approach hierarchy, was used to estimate
occupational inhalation exposure concentrations for both the unloading of NMP from bulk containers
and from drums. For modeling of these air concentrations, EPA attempted to address variability in input
parameters by estimating both central tendency and high-end parameter \ alues. Additionally, EPA used
Monte Carlo simulation to capture variability in input parameters. I-P.\ expects the duration of
inhalation and dermal exposure to be realistic, as the duration is based on the length of time to load
NMP into drums.
Primary Limitations
The representativeness of the estimates of duration of in halation and dermal exposure for the unloading
activities toward the true distribution of duration for all worker activities in this occupational exposure
scenario is uncertain. NMP concentration is reported to CDR as a range and EPA assessed only the
upper end of the range since a central value cannot be ascertained for this scenario. Skin surface areas
for actual dermal contact are uncertain. EPA did not find data on the use of gloves for this occupational
exposure scenario and assumed glove usage is likely based on judgment. The assumed glove protection
factor values are uncertain. EPA is uncertain of the accuracy of the emission factors used to estimate
fugitive NMP emissions and thereby to model IS MP air concentrations. The representativeness of the
modeling results toward the true distribution of i nhalation concentrations for this occupational exposure
scenario is uncertain.
Overall Confidence
Considering the overall strengths and limitations, the overall confidence of the PBPK input parameters
for this occupational exposure scenario is medium. The studies that support the health concerns for
adverse developmental effects following acute exposure and adverse reproductive effects following
chronic exposure are described abo\ e in Section 3.2. Overall, EPA has high confidence in the health
endpoints and PODs selected lor acute and chronic risk characterization. Section 3.2.6 describes the
justification for this confidence rating
Page 220 of 487
-------
5301
5302
5303
5304
5305
5306
5307
5308
5309
5310
5311
5312
5313
5314
5315
5316
5317
4.2.2.4
PEER REVIEW DRAFT, DO NOT CITE OR QUOTE
Incorporation into Formulation, Mixture, or Reaction Product
Table 4-11. Non-Cancer Risk Estimates for Acute Exposures Following Occupational Use of NMP
in Formulations, Mixtures, or Reaction Products a
Acute Exposure. Peak
moi:
Acute
blood concent
ration
POD.
(mg/l.)
lien chin a r
('max
No
Clo\e
Clo\e
No
(llo\e
(llo\e
k moi:
1 lealtli Effect,
(m»/l.
Kxposur
»lo\e
s PI
s PI
»lo\ e
s PI
s PI
(= Total
Kndpoint iincl Study
)
e l.e\el
s
10
20
s
10
20
1 1 )
DEVELOPMENTA
Central
L EFFECTS
Tendenc
3.49
0.35
0.IS
<.i:
1198
Increased Fetal
216
y
30
Resorptions
(2003; Saillenfait et
aL 2002)
High-
End
53.2
4.39
2.35
4.1
49
a MOEs <30 indicated in bold
b Central tendency means: typical air concentration, 1-hand dermal (445 cm sin lace area exposed), and ccni.ra.1 tendency
NMP weight fraction (EPA expects 100% NMP for this conditio] i nf use) 11 mh-ciid means worst-case air concentration,
2-hand dermal (890 cm2 surface area exposed), and high-end weiuhl
\\1l' liaclinii (EPA expects 100% NMP for this
condition of use).
MOEs calculated for NMP processed into formulations, mixtures or reaction products using central
tendency estimates of acute exposure to NMP are above the benchmark MOE (30). One MOE calculated
using a high-end estimate of acute exposure (during maintenance, bottling, shipping) is below the
benchmark MOE (30) in the absence of glove use; the MOE calculation incorporating a glove protection
factor (PF 10) is abo\ e the benchmark MOE for this condition of use.
Table 4-12. Non-Cancer Kisk Kslimales for Chronic Kxposures Following Occupational Use of
NMP in Formulations. Mixtures, or Reaction Products 11
Health Effect,
Endpoint and
Study
Clironi
c POD.
Al C
(hi
nig/I.)
Exposur
e l.e\el
Chronic Exposure,
Al C (lir ni»/L)
moi:
lien cli in a r
k moi:
(= Total
I T)
No
»lo\e
s
Clo\e
s PI
10
(llo\e
s PI
20
No
«ilo\e
s
Clo\e
s PI
10
(;io\c
s PI
20
REPROIH C I IV
EEFFECTS
Decreased
Fertility
(Exxon. 199i)
183
(aural
Tendency
6.2
0.63
0.32
29
291
570
30
Ihdi-I'nd
403.0
30.9
16.43
0.45
6
11
11 MOEs <30 indicated in bold
b Central tendency means: typical air concentration, 1-hand dermal (445 cm2 surface area exposed), and central tendency
NMP weight fraction (EPA expects 100% NMP for this condition of use). High-end means worst-case air concentration,
2-hand dermal (890 cm2 surface area exposed), and high-end weight NMP fraction (EPA expects 100% NMP for this
condition of use).
MOEs calculated for NMP use in formulations, mixtures or reaction products using central tendency
estimates of chronic exposure to NMP are below the benchmark MOE (30) in the absence of glove use
and above the benchmark MOE with the incorporation of a glove protection factor (PF 10). MOEs
Page 221 of 487
-------
5318
5319
5320
5321
5322
5323
5324
5325
5326
5327
5328
5329
5330
5331
5332
5333
5334
5335
5336
5337
5338
5339
5340
5341
5342
5343
5344
5345
5346
5347
5348
5349
5350
5351
5352
5353
5354
5355
5356
5357
5358
5359
5360
5361
5362
5363
PEER REVIEW DRAFT, DO NOT CITE OR QUOTE
calculated using a high-end estimate of chronic exposure to NMP were below the benchmark MOE (30),
despite glove use (MOE = 6).
EPA considered the assessment approach, the quality of the data, and uncertainties to determine the
level of confidence.
Primary Strengths
EPA assessed dermal exposure to liquids using the most recent CDR data for concentration provided by
industry submitters. Modeling, in the middle of the approach hierarchy, was used to estimate
occupational inhalation exposure concentrations for the unloading of NMP from drums. For modeling of
these air concentrations, EPA attempted to address variability in input parameters by estimating both
central tendency and high-end parameter values. Additionally, EPA used Monte Carlo simulation to
capture variability in input parameters. EPA expects the duration of inhalation and dermal exposure to
be realistic, as the duration is based on the length of time to load NMP into drums l-l\\ assessed worker
inhalation exposure during maintenance, bottling, shipping, and loading of NMP using directly
applicable monitoring data, which is the highest of the approach hierarchy, taken at an adhesive
formulation facility. The data quality rating for the monitoring data used by EPA is high. EPA expects
the duration of inhalation and dermal exposure to be realistic lor the unloading of drums, as the duration
is based on the length of time to load NMP into drums.
Primary Limitations
The representativeness of the estimates of duration of inhalation and dermal exposure for the assessed
activities toward the true distribution of duration for all worker activities in this occupational exposure
scenario is uncertain. NMP concentration is reported to CDR as a range and EPA assessed only the
upper end of the range since a central value cannot be ascertained for this scenario (NMP concentration
is lower in the formulated products) Skin surface areas for actual dermal contact are uncertain. EPA did
not find data on the use of glo\ es for this occupational exposure scenario and assumed glove usage is
likely based on professional judgement. The assumed glove protection factor values are highly
uncertain. EPA estimated worker inhalation exposure concentration during the loading of NMP in solid
formulations using I-IWs OSHA PI-1, for PM)R model ( 013a). which is the lowest
approach on the hierarchy l;.P.\ did not use these inhalation exposure concentrations for the PBPK
modeling because the PlJPk model does not account for solids and because both the inhalation and
dermal exposure potential are captured within other occupational exposure scenarios. EPA is uncertain
of the accuracy of the emission factors used to estimate fugitive NMP emissions and thereby to model
NMP air concentrations. For the maintenance, bottling, shipping, and loading of liquid NMP, the
monitoring data consists of only 7 data points from 1 source. The representativeness of the modeling and
the monitoring data toward the true distribution of inhalation concentrations for these occupational
exposure scenarios is uncertain.
Overall Confidence
Considering the overall strengths and limitations, the overall confidence of the PBPK input parameters
for this occupational exposure scenario is medium. The studies that support the health concerns for
adverse developmental effects following acute exposure and adverse reproductive effects following
chronic exposure are described above in Section 3.2. Overall, EPA has high confidence in the health
endpoints and PODs selected for acute and chronic risk characterization. Section 3.2.6 describes the
justification for this confidence rating.
Page 222 of 487
-------
5364
5365
5366
5367
PEER REVIEW DRAFT, DO NOT CITE OR QUOTE
4.2.2.5 Application of Paints, Coatings, Adhesives and Sealants
Table 4-13. Non-Cancer Risk Estimates for Acute Exposures Following Occupational Use of NMP
1 lealtli KITccl,
Fndpoint iincl Study
Acute
POD.
(max
(m»/L
)
Fxposur
e l.c\cl
Acute Fxposure. Peak
hlood concentration
(m a/I.)
MOF
lien chili a r
k MOF
(= Total
1 1 )
No
alo\e
s
(llo\e
s PF 5
(llo\e
s PI
10
No
alo\ e
s
(llo\e
s PF 5
(llo\e
s PI
10
Spray application
DEVELOPMENTA
L EFFECTS
Increased Fetal
Resorptions
(2003; Saillenfait et
al. 2002)
216
Central
Tendenc
y
0.31
0.07
(i 04
wo
3000
5152
30
High-
End
24.9
4 42
2.23
S.7
49
W7
Roll / curtain application
DEVELOPMENTA
L EFFECTS
Increased Fetal
Resorptions
(2003; Saillenfait et
al. 2002.)
216
Central
Tendenc
y
(i 3d
0.06
(i ii3
714
3514
6880
30
High-
End
24 7
4 :x
2 10
S.S
50
103
Dip application
DEVELOPMENTA
L EFFECTS
Increased Fetal
Resorptions
(2003; Saillenfait
al., 2002)
( cutral
Tendenc
\
0.35
0.10
0.07
623
2067
2092
30
1 IiliIi-
lilKl
24 X
4.36
2.18
8.7
50
99
Brush application
DEVELOPMENTA
L EFFECTS
Increased Fetal
Resorptions
(2003: Sail
al. 2C )
216
Central
Tendenc
y
0.49
0.25
0.22
440
880
1003
30
High-
End
24.8
4.40
2.22
8.7
49
97
a MOEs < 30 are indicaled in hold
b Central tendency means: i> pic;11 air concentration (unless specified otherwise), 1-hand dermal (445 cm2 surface area
exposed), and central tendency NMP weight fraction. High-end means worst-case air concentration (unless specified
otherwise), 2-hand dermal (890 cm2 surface area exposed), and high-end weight NMP fraction.
5368
5369 MOEs calculated for NMP use in the application of paints, coatings, adhesives and sealants using central
5370 tendency estimates of acute exposure to NMP are above the benchmark MOE (30) with glove use (PF
5371 5). MOEs calculated using high-end estimates of acute exposure during (spray, roll/curtain, brush and
5372 dip) application of NMP-containing paints, coatings, adhesives and sealants are below the benchmark
Page 223 of 487
-------
5373
5374
5375
5376
5377
5378
5379
5380
5381
5382
5383
5384
5385
PEER REVIEW DRAFT, DO NOT CITE OR QUOTE
MOE (30) in the absence of glove use (MOE = 9). MOE calculations incorporating a glove protection
factor (PF 5) were above the benchmark MOE for this condition of use.
Table 4-14. Non-Cancer Risk Estimates for Chronic Exposures Following Occupational Use of
NMP in Application of Painl
ts, Coatings, Adhesives and Sealants a
1 lealtli Effect,
Endpoint itncl
Study
Clironi
c POD.
Al C
(lir
m»/l.)
Exposur
e I.cm'I h
Chronic Exposure.
Al C (In* m»/l.)
MOE
lien chili a r
k MOE
(= Total
I T)
No
«ilo\e
s
Clo\e
s l»l 5
Clo\e
s l»l
10
No
«ilo\e
s
Clo\e
s l»l 5
Clo\e
s l»l
10
Spray application
REPRODUCTIV
E EFFECTS
Decreased
Fertility
(Exxon. 1991)
183
Central
Tendency
1.41
0.32
0.19
130
5fifi
076
30
High-End
179.6
31.1
15.70
1.0
5.9
12
E
Loll / curtain app
icalion
REPRODUCTIV
E EFFECTS
Decreased
Fertility
(Exxon. 1991)
183
Central
Tendency
1.36
0.28
(i 14
134
661
1294
30
High-End
17X4
3d 2
14 X2
1.0
(>.l
12
Dip application
REPRODUCTIV
E EFFECTS
Decreased
Fertility
(Exxon. 1991)
1X3
Central
Teiklaic
V
1.55
(147
0.33
1 18
393
556
30
Hiuh-
liiul
170 1
30.8
15.34
1.0
5.9
12
Brush application
REPRODUCTTV
E EFI ECTS
Decreased
Fertility
(Exxc" 1no1)
1X3
(cn I ml
Tcndcnc
\
2.18
1.08
0.95
84
169
194
30
High-
End
179.5
31.1
15.62
1.0
5.9
12
aMOEs 'ii arc indicated in bold
b Central icikIciic> means: typical air concentration (unless specified otherwise), 1-hand dermal (445 cm2 surface area
exposed), and ceiiiral lendcncy NMP weight fraction. High-end means worst-case air concentration (unless specified
otherwise), 2-liand dermal 1890 cm2 surface area exposed), and high-end weight NMP fraction.
MOEs calculated for NMP use in the application of paints, coatings, adhesives and sealants using central
tendency estimates of chronic exposure to NMP and glove use (PF 5) are above the benchmark MOE
(30). MOEs calculated for NMP use in the application of paints, coatings, adhesives and sealants using
high-end estimates of chronic NMP exposure (e.g., spray, roll/curtain, brush and dip application) are
below the benchmark MOE (30) despite glove use (PF 10).
EPA considered the assessment approach, the quality of the data, and uncertainties to determine the
level of confidence.
Page 224 of 487
-------
5386
5387
5388
5389
5390
5391
5392
5393
5394
5395
5396
5397
5398
5399
5400
5401
5402
5403
5404
5405
5406
5407
5408
5409
5410
5411
5412
5413
5414
5415
5416
5417
5418
5419
5420
5421
5422
5423
5424
5425
5426
5427
PEER REVIEW DRAFT, DO NOT CITE OR QUOTE
Primary Strengths
EPA assessed dermal exposure to central tendency and high-end NMP weight fractions, calculated as
the 50th and 95th percentiles, respectively, from a variety of data sources with data quality ratings
ranging from medium to high. To estimate inhalation exposure during spray application, EPA used
directly applicable personal monitoring data, the highest of the approach hierarchy, including 26 data
points. These data have a data quality rating of high. To estimate inhalation exposure during roll/curtain
application, EPA used modeling, which is in the middle of the approach hierarchy. To estimate
inhalation exposure during dip application, EPA used surrogate monitoring data for dip cleaning, which
is in the middle of the approach hierarchy, including data from 5 sources. These data have data quality
ratings of medium to high. To estimate inhalation exposure during roller / brush and syringe/bead
application, EPA used modeled data from the RIVM report (K ; ), which has a data quality
rating of high. The use of modeling is in the middle of the approach hierarchy. I-PA used durations
associated with short-term inhalation monitoring data to estimate duration of inhalation and dermal
exposure during spray application.
Primary Limitations
For occupational exposure scenarios other than spray application. I-PA did not find exposure duration
data and assumed a high-end of 8 hours because the surrogate data or modeled values are 8-hour TWA
values. EPA assumed a mid-range of 4 hours for central tendency exposure duration. The
representativeness of the assumed estimates of duration of inhalation and dermal exposure for the
assessed activities toward the true distribution of duration for all worker activities in this occupational
exposure scenario is uncertain. Skin surface areas lor actual dermal contact are uncertain. EPA did not
find data on the use of gloves for this occupational exposure scenario and assumed glove usage with
minimal to no employee training or no glove usage due to the wide-spread use of paint, coating,
adhesive, and sealant products The assumed glove protection factor values are highly uncertain. The
available monitoring data lor spray application is from 1996 and the surrogate monitoring data used in
the model for roll / cunain application is from 1994 or earlier. The extent to which these data are
representative of current worker inhalation exposure potential is uncertain. The worker activities
associated with the surrogate data used to assess worker inhalation exposure during dip application are
not detailed for all sample points The modeled inhalation exposure concentration during roller / brush
application was obtained from RIVM ( ! J) and not generated by EPA. For all occupational exposure
scenarios. representati\ eness of the monitoring data, surrogate monitoring data, or modeled data toward
the true distribution of inhalation concentrations for this occupational exposure scenario is uncertain.
Overall Coiifiilciicc
Considering the o\ erall strengths and limitations, the overall confidence of the PBPK input parameters
for this occupational exposure scenario is medium. The studies that support the health concerns for
adverse developmental effects following acute exposure and adverse reproductive effects following
chronic exposure are described above in Section 3.2. Overall, EPA has high confidence in the health
endpoints and PODs selected for acute and chronic risk characterization. Section 3.2.6 describes the
justification for this confidence rating.
Page 225 of 487
-------
5428
5429
5430
5431
5432
5433
5434
5435
5436
5437
4.2.2.6
PEER REVIEW DRAFT, DO NOT CITE OR QUOTE
Printing and Writing
Table 4-15. Non-Cancer Risk Estimates for Acute Exposures Following Occupational Use of NMP
in Printing and Writing a
Health KITect, Kndpoint
and Study
Acute
POD.
(max
(ni«./l.)
Kxposure
Lex el
Acute Kxposure,
Peak blood
concentration
\
oi:
lien chili ark
moi:
(= Total
1 1 )
No
gloxes
(iloxes
PI 5
No
«>lox es
(iloxes
PI 5
Prin I in»
DEVELOPMENTAL
EFFECTS
Increased Fetal
Resorptions
(2003; Saillenfait et at..
2002)
216
Central
Tendency
(i lh
() 15
:xh
1433
30
High-End
: s
0,55
78
3^5
Writing'
DEVELOPMENTAL
EFFECTS
Increased Fetal
Resorptions
(2003; Saillenfait et al„
2002)
216
Central
Tendency
n D009
O.Diiii | v
23 2.401
1,165,010
30
High-End
i) (i(i(i37
1 16.201
582,823
aMOEs < 30 are indicated in bold
bFor printing, central tendency me;nis central tendency (5()lh percentile) air concentration, 1-hand dermal (445 cm2 surface
area exposed), and central tendency W1P w eight fraction. High-end means worst-case (95th percentile) air concentration,
2-hand dermal (890 enr surface area exposed), and high-end weight NMP fraction.
0 For writing, central tendency means dermal exposure over 1 enr surface area exposed [incidental contact] and central
tendency NMP weight fraction. High-end means dermal o\ er 1 enr surface area exposed [incidental contact], and high-
end weight \\1l' fraction. 1P \ expects inhalation exposure lo NMP during writing is negligible.
MOEs calculated for NMP use in |ninlinu and writing using high-end estimates of acute exposure are
above the benchmark MOE (3D) in the absence of glove use. Central tendency and high-end estimates of
acute exposure are above the benchmark MOE (30) with glove use (PF 5).
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5447
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5449
5450
5451
5452
5453
5454
5455
5456
5457
5458
5459
PEER REVIEW DRAFT, DO NOT CITE OR QUOTE
Table 4-16. Non-Cancer Risk Estimates for Chronic Exposures Following Occupational Use of
NMP in Printing and Writ
tinga
Health KITecl, Kndpoinl
;iihI Study
Chronic
l»()l).
Al C
(In
mg/1.)
Kxposure
Le\el
Chronic Kxposure,
Al C (lir ni»/l.)
moi:
lien cli in ark
moi:
(= Total
1 1 )
No
"lOM'S
(iloM'S
l»l 5
No
gloM'S
(ilOM'S
l»l 5
Printing b
REPRODUCTIVE
EFFECTS
Decreased Fertility
(Exxon, i (>'» 1)
183
Central
Tendency
3.4
0.6S
54
269
30
High-End
19.5
3.S
4).4
48
Writing 1
REPRODUCTIVE
EFFECTS
Decreased Fertility
(Exxon. 1 r>c> [)
183
Central
Tendency
16
0.000316
115,998
578.327
30
High-End
0.0032
0.000633
57,998
289,149
11 MOEs < 30 are indicated in bold
bForprinting, central tendency means: central tendencs n<> percentile) air concern ration. 1-hand dermal (445 cm2 surface
area exposed), and central tendency NMP weight fraction 11 mli-cnd means wnrsi-case C95lh percentile) air concentration,
2-hand dermal (890 cm2 surface area exposed), and hmh-eiid u eiuhl NMP fraction
0 For writing, central tendency means: dermal exposure o\ cr 1 cm surface area exposed incidental contact] and central
tendency NMP weight fraction. High-end means dermal n\ cr 1 cm surface area exposed [incidental contact], and high-
end weight NMP fraction. EPA expects inhalation exposure in W1P durum u ruing is negligible.
MOEs calculated for \MP use in priming and writing using central tendency estimates of chronic
exposure are above the benchmark MOE (30) with glove use (PF 5). One MOE calculated using a high-
end estimate of chronic exposure during priming is below the benchmark MOE in the absence of glove
use; the MOE calculated incorporating a glo\ e protection factor (PF 5) is above the benchmark MOE for
this condition of use The MOI- calculated for NMP use in writing using a high-end estimate of chronic
exposure is above the benchmark MOI- (30) in the absence of glove use.
EPA considered the assessment approach, the quality of the data, and uncertainties to determine the
level of conJi dence
Primary Stream/is
For printing activities. I -PA assessed dermal exposure to central tendency and high-end NMP weight
fractions, calculated as the 50lh and 95th percentiles, respectively, from a variety of data sources with
data quality ratings of high. For writing activities, EPA assessed dermal exposure to 1 to 2% NMP based
on one writing product identified in the Use and Market Profile for N-Methylpyrrolidone (Abt ).
For worker dermal exposure during writing, EPA determined the skin surface area dermally exposed to
writing ink using a literature source with a data quality rating of high. To estimate worker inhalation
exposure during printing, EPA used surrogate monitoring data, which is in the middle of the approach
hierarchy. These data include 48 samples and have a data quality rating of high. EPA used durations
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5476
5477
5478
5479
5480
5481
5482
5483
5484
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PEER REVIEW DRAFT, DO NOT CITE OR QUOTE
associated with inhalation monitoring data to estimate duration of inhalation and dermal exposure during
printing activities.
Primary Limitations
For writing, EPA did not find exposure duration data and assumed a high-end of 8 hours based on the
length of a full shift and a central tendency of 4 hours based on the mid-range of a shift. The
representativeness of the assumed estimates of duration of inhalation and dermal exposure for the
assessed printing and writing activities toward the true distribution of duration for all worker activities in
this occupational exposure scenario is uncertain. For printing, skin surface areas for actual dermal
contact are uncertain. EPA did not find data on glove usage. For printing activities, EPA assumed glove
usage with minimal to no employee training or no glove usage due to the u i de-spread use of ink
products. The assumed glove protection factor values are highly uncertain I-'or u l iting activities, EPA
assumed glove usage is unlikely for the use of markers, based on engineering judgement. The surrogate
monitoring data used to estimate occupational inhalation exposure during printing is from 1983. The
extent to which these data are representative of current worker inhalation exposure potential is uncertain.
The representativeness of the surrogate monitoring data toward the true distribution of inhalation
concentrations for this occupational exposure scenario is uncertain
Overall Confidence
Considering the overall strengths and limitations, the overall confidence of the PBPK input parameters
for this occupational exposure scenario is medium The studies that support the health concerns for
adverse developmental effects following acute exposure and adverse reproductive effects following
chronic exposure are described above in Section 3.2. 0\ erall, EPA has high confidence in the health
endpoints and PODs selected for acute and chronic risk characterization. Section 3.2.6 describes the
justification for this confidence rating
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5489
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5492
5493
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PEER REVIEW DRAFT, DO NOT CITE OR QUOTE
4.2.2.7 Metal Finishing
Table 4-17. Non-Cancer Risk Estimates for Acute Exposures Following Occupational Use of NMP
in Metal Finishing a
Acute Kxposure, Peak
Acute
hlood concent
ration
POD.
(mg/l.)
moi:
lien chili a r
(max
No
(llo\e
No
(llo\e
k moi:
1 lealtli KITccl,
(m»/L
Kxposur
»lo\e
(llo\e
s PI
»lo\ e
(llo\e
s PI
(= Total
Kndpoint iincl Study
)
e l.e\el
s
s PI 5
10
s
s PI 5
It)
1 1 )
Spray application
DEVELOPMENTA
Central
L EFFECTS
Tendenc
9.49
1.83
0
23
1 IS
235
Increased Fetal
216
y
30
Resorptions
(2003; Saillenfait et
al. 2002)
High-
End
46.3
7 54
3.72
4.7
29
5X
Dip application
DEVELOPMENTA
Central
L EFFECTS
Tendenc
0
1.87
0 i>5
23
116
227
Increased Fetal
216
y
30
Resorptions
High-
End
(2003; Saillenfait et
al. 2002.)
4^:
7 4w
3 67
4.7
29
59
Brush application
DEVELOPMENTA
Central
L EFFECTS
Tcndcnc
9.69
2.01
1.09
22
107
198
Increased Fetal
\
30
Resorptions
1 liijh-
IjkI
(2003; Saillenfait
al., 2002)
4ft 3
7.53
3.71
4.7
29
58
11 MOEs < 30 arc indicate
d mi hold
b Central tendency means
l\ pical a
r cuiicciiiralimi (unless specified otherwise), 1-hand dermal (445 cm2 surface area
exposed), and central tendenc} W1P weight fraction. High-end means worst-case air concentration (unless specified
otherwise). 2-liand dermal (89< > cm surface area exposed), and high-end weight NMP fraction.
MOEs calculated lor WIP use in metal finishing using central tendency estimates of acute exposure are
above the benchmark MOI ! (30) with glove use (PF 5). MOEs calculated using high-end estimates of
acute exposure to NM P during metal finishing (e.g., spray, dip and brush application) are below the
benchmark MOE (30) in the absence of glove use; MOE calculations incorporating a glove protection
factor (PF 10) are above the benchmark MOE (30) for this condition of use.
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5504
5505
5506
5507
5508
5509
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5511
5512
5513
5514
PEER REVIEW DRAFT, DO NOT CITE OR QUOTE
Table 4-18. Non-Cancer Risk Estimates for Chronic Exposures Following Occupational Use of
NMP in Metal Finishing a
1 Icallli EITccl,
Kndpoint and
Sliulv
Clironi
c POD.
Al C
(lir
m»/l.)
Kxposur
el,e\el
Chronic Exposure,
Alt' (lir m»/l.)
MOE
lien cli mar
u moi:
(= lolal
1 1 )
No
»lo\e
s
(il0M'
s PI 5
(Jo\C
s PI
10
No
«ilo\o
s
(Jo\C
s PI 5
(IIOM'
s PI
10
Spray application
REPRODUCTIV
E EFFECTS
Decreased
Fertility
(Exxon. 1991)
183
Central
Tendency
44
8.31
4.15
4.2
22
44
30
High-End
347
53
26
0.5
3.4
7.0
Dip application
REPRODUCTIV
E EFFECTS
Decreased
Fertility
(Exxon. 1991)
183
Central
Tendency
44
8.46
4 29
4.2
22
43
30
High-End
346
53.0
25 X5
0.5
3.5
7.1
Brush application
REPRODUCTIV
E EFFECTS
Decreased
Fertility
(Exxon. 1991)
183
Central
Tendency
45
w.l
4^2
4.1
20
37
30
High-End
347
53.3
2ft 14
0.5
3.4
7.0
11 MOEs < 30 are indicated mi hold
b Central tendency means: l\ pical air concentration (unless specified otherwise), 1-hand dermal (445 cm2 surface area
exposed), and central tendency \'\1P ueidii fraction High-end means worst-case air concentration (unless specified
otherwise), 2-hand dermal < S')i i an surface area exposed), and high-end weight NMP fraction.
MOEs calculated for NMP use in metal finishing (e.g., spray, dip and brush application) using central
tendency estimates of chronic exposure are below the benchmark MOE (30) with glove use (PF 5).
MOEs calculated using high-end estimates of chronic exposure to NMP during metal finishing (e.g.,
spray, dip and brush application) are below the benchmark MOE (30) with glove use (PF 10).
EPA considered the assessment approach, the quality of the data, and uncertainties to determine the
level of confidence
Primary Strengths
EPA assessed dermal exposure to liquids using the most recent CDR data for concentration provided by
industry submitters. To estimate inhalation exposure during spray application, EPA used surrogate
monitoring data, which is in the middle of the approach hierarchy, including 26 data points. These data
have a data quality rating of high. To estimate inhalation exposure during dip application, EPA used
surrogate monitoring data for dip cleaning, which is in the middle of the approach hierarchy, including
data from 5 sources. These data have data quality ratings of medium to high. To estimate inhalation
exposure during brush application, EPA used modeled data from the RIVM report (RIVM.! ), which
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5523
5524
5525
5526
5527
5528
5529
5530
5531
5532
5533
5534
5535
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5537
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PEER REVIEW DRAFT, DO NOT CITE OR QUOTE
has a data quality rating of high. The use of modeling is in the middle of the approach hierarchy. EPA
used durations associated with inhalation monitoring data to estimate duration of inhalation and dermal
exposure during spray application.
Primary Limitations
For occupational exposure scenarios other than spray application, EPA did not find exposure duration
data and assumed a high-end of 8 hours because the surrogate data or modeled values are 8-hour TWA
values. EPA assumed a mid-range of 4 hours for central tendency exposure duration. The
representativeness of the assumed estimates of duration of inhalation and dermal exposure for the
assessed activities toward the true distribution of duration for all worker activities in this occupational
exposure scenario is uncertain. Due to lack of data, EPA could not calculate central tendency and high-
end NMP concentration in metal finishing products and used the low-end and high-end of the NMP
concentration range reported in 2016 CDR. Skin surface areas for actual dermal contact are uncertain.
EPA did not find data on the use of gloves for this occupational exposure scenario and assumed glove
usage with minimal to no employee training or no glove usage due to the potential w ide-spread use of
metal finishing products. The assumed glove protection factor values are highly uncertain. The available
monitoring data for spray application is from 1996. The extent to u hich these data are representative of
current worker inhalation exposure potential is uncertain The worker activities associated with the
surrogate data used to assess worker inhalation exposure during dip application are not detailed for all
sample points. The modeled inhalation exposure concentration during roller/brush application was
obtained from RIVM (2013) and not generated by N\\ For all occupational exposure scenarios,
representativeness of the monitoring data, surrogate monitoring data, or modeled data toward the true
distribution of inhalation concentrations for this occupational exposure scenario is uncertain.
Overall Confidence
Considering the overall strengths and limitations, the overall confidence of the PBPK input parameters
for this occupational exposure scenario is medium. The studies that support the health concerns for
adverse developmental effects following acute exposure and adverse reproductive effects following
chronic exposure are described above in Section 3 2 Overall, EPA has high confidence in the health
endpoints and PODs selected for acute and chronic risk characterization. Section 3.2.6 describes the
justification for this confidence rating
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5557
5558
5559
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4.2.2.8
PEER REVIEW DRAFT, DO NOT CITE OR QUOTE
Removal of Paints, Coatings, Adhesives and Sealants
Table 4-19. Non-Cancer Risk Estimates for Acute Exposures Following Occupational Use of NMP
in the Removal of Paints, Coatings, Adhesives and Sealants a
Acute Kxposure, Peak
Acute
blood concent
ration
POD.
(nig/I.)
moi:
lien chili a r
(max
No
doxe
No
(lloXC
k moi:
1 Icaltli K fleet.
(m»/l.
Kxposur
»lo\c
doxe
s PI
»l ox e
(lloXC
S PI
(= Total
Knilpoint :iikI Sluilv
)
e l.exel h
s
s PI 5
1(1
s
s PI 5
It)
1 1 )
Miscellaneous removal
DEVELOPMENTA
Central
L EFFECTS
Tendenc
2.07
0.51
t).3l
104
425
ft87
Increased Fetal
216
y
30
Resorptions
(2003; Saillenfait et
al. 2002)
High-
End
36.5
7.71
4.72
5.9
28
4ft
Graffiti rem ox a 1
DEVELOPMENTA
Central
L EFFECTS
Tendenc
7 xw
1.56
(i So
27
138
270
Increased Fetal
216
y
30
Resorptions
High-
End
(2003; Saillenfait et
2K> 2
5.07
2 55
7.4
43
85
al. 2002.)
a MOEs < 30 are indicated in bold
b Central tendency means: mid-range or mean air concentration. 1-liand dermal (445 cm2 surface area exposed), and
central tendency NMP weight fraction. 1 hull-end means higli-end air
concentration, 2-hand dermal (890 cm2 surface area
exposed), and high-end w
/eight NMP fraction.
The MOE calculated for NMP use in miscellaneous removal of paints, coatings, adhesives and sealants
using a high-end estimate of acute exposure is below the benchmark MOE (30) in the absence of glove
use; the MOE calculated using a high-end estimate of acute exposure with glove use (PF 10) is above
the benchmark MOE. The MOli calculated for NMP use in miscellaneous removal of paints, coatings,
adhesives and sealants using a central tendency estimate of acute exposure is above the benchmark
MOE (30) with glove use (PF 5) MOEs calculated for NMP use in graffiti removal using central
tendency and high-end estimates of acute exposure with glove use (PF = 5) are above the benchmark
MOE (30).
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5570
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5573
5574
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5576
5577
5578
5579
5580
5581
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PEER REVIEW DRAFT, DO NOT CITE OR QUOTE
Table 4-20. Non-Cancer Risk Estimates for Chronic Exposures Following Occupational Use of
NMP in the Removal of Paints, Coatings, Adhesives and Sealants a
1 leallli El'lccl,
Kndpoint and
Sluilv
C 'h roil i
c POD.
Al C
(lir
m»/E)
Exposiir
oEom-I
Chronic Exposure,
Alt' (lir m»/l.)
MOE
lien chin a r
k moi:
(= lolal
1 1 )
No
»lo\e
s
Glo\C
s PI 5
Glo\C
s PI
10
No
«ilo\o
s
(ilo\ c
s l»l 5
Glo\C
s PI
10
Miscellaneous removal
REPRODUCTIV
E EFFECTS
Decreased
Fertility
(Exxon. 1991)
183
Central
Tendency
5.55
1.4
0.84
33
135
218
30
High-End
268
54
33
0.7
3.4
5.6
Graf
iti removal
REPRODUCTIV
E EFFECTS
Decreased
Fertility
(Exxon. 1991)
183
Central
Tendency
36.3
7.1
3 61
5.0
26
51
30
High-End
212
36
IS
O.M
5.1
10
11 MOEs < 30 are indicated in bold
b Central tendency means: mid-range or mean air cuiiceiilialimi. 1 -hand dermal (445 cm surface area exposed), and
central tendency NMP weight fraction. High-end means hiuh-end air coiiceiiuauon. 2-hand dermal (890 cm2 surface area
exposed), and high-end weight NMP fraction.
The MOE calculated for NMP use in miscellaneous removal of paints, coatings, adhesives and sealants
using a central tendency estimate (if chronic exposure is above the benchmark MOE (30) with glove use
(PF 5). MOEs calculated based on hiuh-end estimates for chronic exposure during the removal of paints,
coatings, adhesives and sealants (i e., miscellaneous removal and graffiti removal) are below the
benchmark MOI- (3D) with ulo\e use (PF 10).
EPA considered the assessment approach, the quality of the data, and uncertainties to determine the
level of confidence.
Primary Strengths
EPA assessed dermal exposure to central tendency and high-end NMP weight fractions, calculated as
the 50th and 95th percentiles, respectively, from a variety of data sources with data quality ratings
ranging from medium to high. To estimate inhalation exposure during miscellaneous paint and coating
removal, EPA used directly applicable personal monitoring data, the highest of the approach hierarchy,
including data from three studies. These data have a data quality rating of high. To estimate inhalation
exposure during graffiti removal, EPA used directly applicable personal monitoring data, the highest of
the approach hierarchy, including 25 data points. These data have a data quality rating of high. EPA
used durations associated with inhalation monitoring data to estimate duration of inhalation and dermal
exposure during miscellaneous paint and coating removal.
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5593
5594
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5596
5597
5598
5599
5600
5601
5602
5603
5604
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5607
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Primary Limitations
For graffiti removal, EPA did not find data other than 8-hour TWA values. EPA assumed a high-end
exposure duration equal to 8 hours and a central tendency exposure duration of 4 hours, which is the
mid-range of a full shift. The representativeness of the assumed estimates of duration of inhalation and
dermal exposure for the assessed activities toward the true distribution of duration for all worker
activities in this occupational exposure scenario is uncertain. EPA did not find data on the use of gloves
for this occupational exposure scenario and assumed glove usage with minimal to no employee training
or no glove usage due to the wide-spread use of removal products. The assumed glove protection factor
values are highly uncertain. The short-term inhalation exposure concentrations for miscellaneous
removal are based on data from 1993 and the extent to which these data arc representative of current
worker inhalation exposure potential is uncertain. For graffiti removal. I -PA used the minimum, mean,
and maximum air concentrations reported by one literature source for 25 datapoints. EPA did not have
these 25 data points with which to calculate 50th and 95th percentile values. The representativeness of
the monitoring data toward the true distribution of inhalation concentrations for this occupational
exposure scenario is uncertain.
Overall Confidence
Considering the overall strengths and limitations, the o\ era 11 confidence of the PBPK input parameters
for this occupational exposure scenario is medium. The studies that support the health concerns for
adverse developmental effects following acute exposure and ad\ ei se reproductive effects following
chronic exposure are described above in Section 3 2. ()\ erall, EPA has high confidence in the health
endpoints and PODs selected for acute and chronic risk characterization Section 3.2.6 describes the
justification for this confidence rating.
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4.2.2.9 Cleaning
Table 4-21. Non-Cancer Risk Estimates for Acute Exposures Following Occupational Use of NMP
in Cleaning a
Acute Kxposure, Peak
Acute
hlood concent
ration
POD.
(mg/l.)
moi:
lien chin a r
(max
No
(llo\e
No
(llo\e
k moi:
1 lealtli KITcct,
(mg/L
Kxposur
»lo\e
(llo\e
s PI
»lo\ e
(llo\e
s PI
(= Total
Kndpoint iincl Study
)
e l.e\el
s
s PI 5
10
s
s PI 5
10
1 1 )
Dip cleaning
DEVELOPMENTA
Central
L EFFECTS
Tendenc
13.7
2.62
1 32
16
82
163
Increased Fetal
216
y
30
Resorptions
(2003; Saillenfait et
al. 2002)
High-
End
52.6
8.36
4.07
4.1
26
53
Spray / wipe cleaning
DEVELOPMENTA
Central
L EFFECTS
Tendenc
4 88
0.99
() 52
44
218
418
Increased Fetal
216
y
30
Resorptions
High-
End
(2003; Saillenfait et
al. 2002.)
52 i)
8 20
4 i>5
4.2
26
53
a MOEs < 30 are indicated in bold
b Central tendency means: central lendeiics < 5<>
percentile) air concentration. 1 -hand dermal (445 cm2 surface area
exposed), and central tendency NMP weidil liaclion. High-end means high-end (95th percentile) air concentration, 2-hand
dermal (890 cm2 surface area exposed), and hmh-cnd weight NMP fraction.
MOEs calculated for NMP use in cleaning applications (e.g., dip and spray/wipe cleaning) based on
central tendency estimates of acute exposure are above the benchmark MOE (30) with glove use (PF 5).
MOEs calculated for NMP use in cleaning applications based on high-end estimates of acute exposure
are below the benchmark MOI- (3d) in ihe absence of glove use; MOEs calculated for NMP use in
cleaning applications based on high-end estimates of acute exposure incorporating a glove protection
factor (PI ' 11)) are above the benchmark MOE.
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5637
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PEER REVIEW DRAFT, DO NOT CITE OR QUOTE
Table 4-22. Non-Cancer Risk Estimates for Chronic Exposures Following Occupational Use of
NMP in Cleaning a
1 leallli EITccl,
Kndpoinl ;iikI
Sliulv
C hroili
c POD.
Al C
(lir
mg/l.)
Kxposiir
e I.cm'I
Chronic Exposure,
Alt' (lir m»/l.)
MOE
lien chili a r
k moi:
(= lolal
1 1 )
No
»lo\e
s
(Jo\C
s PI 5
(Jo\C
s PI
10
No
glo\e
s
do\C
s l»l 5
(Jo\C
s PI
10
Dip cleaning
REPRODUCTIV
E EFFECTS
Decreased
Fertility
(Exxon. 1991)
183
Central
Tendency
64.0
12
5.99
2.«>
15
31
30
High-End
399
59
29
0.5
3.1
6.4
Spray / wipe cleaning
REPRODUCTIV
E EFFECTS
Decreased
Fertility
(Exxon. 1991)
183
Central
Tendency
22.3
4.5
2 33
8.2
41
7w
30
High-End
393
59
0.5
3.1
6.4
11 MOEs < 30 are indicated in bold
b Central tendency means: central tendency (50th peiceiiii lei air concern ralion. l-haiid dermal (445 cm2 surface area
exposed), and central tendency NMP weight fraction 1 hull-end means hiuli-end (95 percentile) air concentration, 2-hand
dermal (890 cm2 surface area exposed), and high-end uemlil W1P fraction
The MOE calculated lor NMP use in clip cleaning based on a central tendency estimate of chronic
exposure is below the benchmark MOli (30) with glove use (PF 5); the MOE calculated for NMP use in
spray/wipe cleaning based on a central tendency estimate of chronic exposure is above the benchmark
MOE (30) with glove use (PF 5) \l()l-s calculated for NMP use in cleaning applications (i.e., dip,
spray/wipe cleaning) using high-end estimates of chronic exposure and glove use (PF 10) are below the
benchmark MOE.
EPA considered the assessment approach, the quality of the data, and uncertainties to determine the
level of confidence.
Primary Strengths
EPA assessed dermal exposure to central tendency and high-end NMP weight fractions, calculated as
the 50th and 95th percentiles, respectively, from a variety of data sources with data quality ratings
ranging from medium to high. To estimate inhalation exposure during dip cleaning, EPA used directly
applicable monitoring data, which is in the highest of the approach hierarchy, including data from 5
sources. These data have data quality ratings ranging from medium to high. To estimate inhalation
exposure during spray / wipe application, EPA used directly applicable monitoring data, which is in the
highest of the approach hierarchy, including data from 4 sources. These data have data quality ratings
ranging from medium to high.
Page 236 of 487
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5642
5643
5644
5645
5646
5647
5648
5649
5650
5651
5652
5653
5654
5655
5656
5657
5658
5659
5660
5661
5662
5663
5664
5665
5666
5667
5668
5669
5670
5671
PEER REVIEW DRAFT, DO NOT CITE OR QUOTE
Primary Limitations
EPA did not find exposure duration data and assumed a high-end of 8 hours based on the length of a full
shift and a central tendency of 4 hours based on the mid-range of a shift. The representativeness of the
assumed estimates of duration of inhalation and dermal exposure for the assessed cleaning activities
toward the true distribution of duration for all worker activities in this occupational exposure scenario is
uncertain. Skin surface areas for actual dermal contact are uncertain. EPA did not find data on the use of
gloves for this occupational exposure scenario and assumed glove usage with minimal to no employee
training or no glove usage due to the wide-spread use of cleaning products. The assumed glove
protection factor values are highly uncertain. The worker activities associated with the monitoring data
used to assess inhalation exposure during dip cleaning and spray/wipe cleaning were not detailed for all
samples. Where EPA could not determine the type of cleaning activities associated with a data point,
EPA used the data in the estimates for both dip and spray/wipe cleaning. For holli occupational exposure
scenarios, the representativeness of the monitoring data toward the true distribution of inhalation
concentrations for this occupational exposure scenario is uncertain.
Overall Confidence
Considering the overall strengths and limitations, the o\ era 11 confidence of the PBPK input parameters
for this occupational exposure scenario is medium. The studies that support the health concerns for
adverse developmental effects following acute exposure and ad\ cise reproductive effects following
chronic exposure are described above in Section 3 2 ()\ erall, EIW has hiuli confidence in the health
endpoints and PODs selected for acute and chronic risk characterization Section 3.2.6 describes the
justification for this confidence rating.
4.2.2.10 Commercial Automotive Servicing
Table 4-23. Non-Csinoer Kisk Estimates for Acute Exposures Following Occupational Use of NMP
in Commercial Automotive Servicing "
Acute Exposure. Peak
Acute
blood concent
ration
POD.
(mg/l.)
moi:
lien chin a r
(in :t \
No
(Jo\e
No
(Jo\e
k moi:
1 lealtli Effect.
(ni»/l.
Kxposur
»lo\e
(llo\e
s PI
»lo\ e
(llo\e
s PI
(= Total
Kndpoint iincl Study
)
e l.e\el
s
s PI 5
It)
s
s l»l 5
It)
1 1 )
DEVEI.OPM K\TA
('ailxal
L El 1 EC I S
Taulenc
0.35
0.21
0.20
624
1009
1090
Increased Fet:il
21 ft
\
30
Resorptions
(2003; Saillenfait et
aL 2002)
lh»h-
End
15.9
3.93
2.59
14
55
84
aMOEs < are 30 indicated in bold
b Central tendency means: central tendency (50th percentile) air concentration, 1-hand dermal (445 cm2 surface area
exposed), and central tendency NMP weight fraction. High-end means high-end (95th percentile) air concentration, 2-hand
dermal (890 cm2 surface area exposed), and high-end weight NMP fraction.
MOEs calculated for NMP use in commercial automotive servicing based on high-end estimates of acute
exposure are below the benchmark MOE (30) in the absence of glove use. MOEs calculated for NMP
Page 237 of 487
-------
5672
5673
5674
5675
5676
5677
5678
5679
5680
5681
5682
5683
5684
5685
5686
5687
5688
5689
5690
5691
5692
5693
5694
5695
5696
5697
5698
5699
5700
5701
5702
5703
PEER REVIEW DRAFT, DO NOT CITE OR QUOTE
use in commercial automotive servicing based on central tendency and high-end estimates of acute
exposure to workers are above the benchmark MOE (30) with glove use (PF = 5).
Table 4-24. Non-Cancer Risk Estimates for Chronic Exposures Following Occupational Use of
NMP in Commercial Automotive Servicing a
Chroni
Chronic Kxposiirc,
c POD.
Al C (lir m»/l.)
moi:
lien chili ar
1 lealtli Illicit,
Al C
No
(Jo\C
No
(i lo\c
k moi:
Kiulpoint and
(In
Kxposur
»lo\e
(Jo\C
S PI
«ilo\e
(ilo\ 0
s PI
(= Total
St nil v
nig/I.)
e I.cm'I h
s
s PI 5
10
s
s l»l 5
10
1 1 )
REPRODUCTIV
E EFFECTS
Decreased
183
Central
Tendency
0.92
0.6
0.53
1 yy
3 1 <¦)
344
30
Fertility
(Exxon. 1991)
High-End
113
27
18
1.6
6.7
10
a MOEs < 30 are indicated in red.
b Central tendency means: central tendency (50th percentile) air concent ration,
exposed), and central tendency NMP weight fraction. High-end means hidi-ei
dermal (890 cm2 surface area exposed), and high-end weight NMP fraction
l-haiid dermal (445 cm surface area
id (l>5h percentile) air concentration, 2-hand
The MOE calculated for NMP use in commercial automotive servicing (i e . aerosol degreasing) based
on high-end estimates of acute exposure is below the benchmark MOI- (3D) in the absence of glove use.
MOEs calculated for NMP use in commercial aulomoli\ e ser\ icing based on central tendency estimates
of chronic NMP exposure are below the benchmark MOI- (3D) with glove use (PF 10).
EPA considered the assessment approach, the quality of the data, and uncertainties to determine the
level of confidence.
Primary Strengths
EPA assessed dermal exposure to central tendency and high-end NMP weight fractions, calculated as
the 50th and 95th percentiles, respecti\ ely, from a variety of data sources with data quality ratings of
high. Modeling, in the middle of the approach hierarchy, was used to estimate occupational inhalation
exposure concentrations. For modeling of these air concentrations, EPA attempted to address variability
in input parameters by estimating both central tendency and high-end parameter values. Additionally,
EPA used Monle Carlo simulation to capture variability in input parameters. EPA expects the duration
of inhalation and dermal exposure to be realistic, as the duration is based on the length of time to
conduct aerosol degreasing of automotive brakes.
Primary Limitations
The representativeness of the estimates of duration of inhalation and dermal exposure for the aerosol
brake degreasing activities toward the true distribution of duration for all worker activities in this
occupational exposure scenario is uncertain. Skin surface areas for actual dermal contact are uncertain.
EPA did not find data on the use of gloves for this occupational exposure scenario and assumed glove
usage with minimal to no employee training or no glove usage due to the wide-spread use of degreasing
products. The assumed glove protection factor values are highly uncertain. For the modeling of NMP air
concentrations, EPA used aerosol product use rate and application frequency from one literature source
(CARB. 2000) on brake servicing. The extent to which this is representative of other aerosol degreasing
Page 238 of 487
-------
5704
5705
5706
5707
5708
5709
5710
5711
5712
5713
5714
5715
5716
5717
5718
5719
5720
5721
5722
5723
5724
PEER REVIEW DRAFT, DO NOT CITE OR QUOTE
applications involving NMP is uncertain. The representativeness of the modeling results toward the true
distribution of inhalation concentrations for this occupational exposure scenario is uncertain.
Overall Confidence
Considering the overall strengths and limitations, the overall confidence of the PBPK input parameters
for this occupational exposure scenario is medium. The studies that support the health concerns for
adverse developmental effects following acute exposure and adverse reproductive effects following
chronic exposure are described above in Section 3.2. Overall, EPA has high confidence in the health
endpoints and PODs selected for acute and chronic risk characterization. Section 3.2.6 describes the
justification for this confidence rating.
4.2.2.11 Laboratory Use
Table 4-25. Non-Cancer Risk Estimates for Acute Exposures Following Occupational Use of NMP
in Laboratories a
1 lealtli Effect,
Endpoint and
St ud v
Anil
e
POD
Cm a
\
(m«i /
I-)
Expos
IIIV
l.e\el ¦'
Acute Exposure, I'eak
blood concentration
(in «•/!.)
moi:
lien chin
ark
MOE
(= Total
1 1 )
No
«lo\
es
(Jtn
es
l»l 5
(,lo\
es
l»l
10
(,lo\
es
l»l
20
No
»lo\
es
(Jtn
es
l»l 5
CUn
es
l»l
10
CUn
es
l»l
20
DEVELOPME
NTAL
EFFECTS
Increased Fetal
Resorptions
(2003;
Saillenfait et al..
Central
Tcndcn
c\
1 (> 4
2.0
1 0
(i 50
21
107
214
428
30
1 liijh-
LikI
52.7
X 4
4 1
2.08
4.1
26
52
104
aMOEs < 30 indicated mi hold.
b Central tendency meuiib. t>pical air concentration. 1-hand dermal (445 cm2 surface area exposed), and central tendency
NMP weight Traction. High-end means worst-case air concentration, 2-hand dermal (890 cm2 surface area exposed), and
high-end wemht \MP fraction.
MOEs calculated bused on high-end estimates of acute exposure during laboratory use of NMP are
below the benchmark MOI - (30) in the absence of glove use. MOEs calculated for laboratory use of
NMP based on high-end estimates of acute exposure are above the benchmark MOE (30), with glove
use (PF 10).
Page 239 of 487
-------
5725
5726
5727
5728
5729
5730
5731
5732
5733
5734
5735
5736
5737
5738
5739
5740
5741
5742
5743
5744
5745
5746
5747
5748
5749
5750
5751
5752
5753
5754
5755
PEER REVIEW DRAFT, DO NOT CITE OR QUOTE
Table 4-26. Non-Cancer Risk Estimates for Chronic Exposures Following Occupational Use of
NMP in Laboratories a
1 lenllli KITecl.
Kndpoinl and
Si ud v
Cliro
nic
POD,
Al C
(lir
m«i/l.)
Kxposu
IT
l.e\elh
Chronic Kxposure, Al C
(lir m»/l.)
moi:
lien chili
ark
moi:
(= Tolsil
I 1 )
No
»lo\
es
CUn
es
PI 5
(Jtn
es
l»l
10
(Jtn
es
PI
20
No
»lo\
es
CUn
es
PI 5
(,lo\
es
PI
10
(,lo\
es
PI
20
RKPkOIH C I
IV E
EFFECTS
Decreased
Fertility
(Exxon. 1991)
183
( ciiiral
lendenc
y
3b
o.y
3.4
1.7
5.0
27
53
107
30
High-
End
400
60
29
15
0.5
3.1
6.3
12
a MOEs < 30 are indicated in bold
b Central tendency means: typical air concentration, 1-hand dermal (445 cm2 surface area exposal). and cciili.il tendency
NMP weight fraction. High-end means worst-case air concentration. 2-liand dermal (890 cm2 surface area exposed), and
high-end weight NMP fraction.
The MOE calculation based on a high-end estimate of chronic exposure to workers during laboratory
use of NMP is below the benchmark MOE (3D) in the absence of glove use; the MOE calculated
incorporating (PF 10) glove use is below the benchmark MOE. MOEs calculated based on central
tendency estimates of chronic exposure to NMP during laboratory use are above the benchmark MOE
(30) with glove use (PF 10).
EPA considered the assessment approach, the quality of the data, and uncertainties to determine the
level of confidence
Primary Strengths
EPA assessed occupational inhalation exposure using directly applicable personal monitoring data,
which is 1he highest of the approach hierarchy, from one source with a data quality rating of medium.
EPA also used a modeled inhalation exposure concentration value, which is in the middle of the
approach hierarchy, from Rl\ M ( ) This data has a data quality rating of high. EPA determined
central tendency exposure duration from the inhalation monitoring data. EPA expects the central
tendency duration of inhalation and dermal exposure to be realistic, as the duration is task-based.
Primary Limitations
EPA assumed a high-end exposure duration of 8 hours based on the length of a full shift. The
representativeness of the assumed estimates of duration of inhalation and dermal exposure for the
assessed activities toward the true distribution of duration for all worker activities in this occupational
exposure scenario is uncertain. EPA did not find NMP concentration data and assumed workers may be
exposed to up to 100% NMP since NMP is a carrier chemical, and carrier chemical concentrations may
be very high. Skin surface areas for actual dermal contact are uncertain. EPA did not find data on the use
of gloves for this occupational exposure scenario and assumed glove usage is likely based on judgment.
The assumed glove protection factor values are highly uncertain. The monitoring data used for central
tendency worker inhalation exposure is only one data point from a 1996 industrial hygiene report. The
extent to which these data are representative of current worker inhalation exposure potential is uncertain.
The modeled high-end inhalation exposure concentration was obtained from RIVM (2013) and not
Page 240 of 487
-------
5756
5757
5758
5759
5760
5761
5762
5763
5764
5765
5766
5767
5768
5769
PEER REVIEW DRAFT, DO NOT CITE OR QUOTE
generated by EPA. The representativeness of the monitoring data and modeled exposure toward the true
distribution of inhalation concentrations for this occupational exposure scenario is uncertain.
Overall Confidence
Considering the overall strengths and limitations, the overall confidence of the PBPK input parameters
for this occupational exposure scenario is medium. The studies that support the health concerns for
adverse developmental effects following acute exposure and adverse reproductive effects following
chronic exposure are described above in Section 3.2. Overall, EPA has high confidence in the health
endpoints and PODs selected for acute and chronic risk characterization. Section 3.2.6 describes the
justification for this confidence rating.
4.2.2.12 Electronic Parts Manufacturing
Table 4-27. Non-Cancer Risk Estimates for Acute Exposures iollowing Occupational Use of NMP
1 lealtli Effect,
Endpoint and Study
Acute
POD.
Cinax
(m»/l.
)
Exposu i'
e l.e\el
Acute Exposure, Peak
blood concentration
moi:
lien chili a r
k moi:
(= Total
1 1 )
No
»lo\e
s
(llo\e
s PI
It)
(llo\e
s PI
20
No
»lo\ e
s
(llo\e
s PI
It)
(llo\e
s PI
20
Container hand
in», small containers
DEVELOPMENTA
L EFFECTS
Increased Fetal
Resorptions
(2003; Saillenfait
al. 2002)
Central
Tendenc
V
) 1 1
1 1
0.54
1')
204
400
30
1 li»h-
lilKl
4m )
1.65
4.7
65
131
Container
landling, drums
DEVELOPMENTA
LEFFECTS
Increased Fetal
Resorptions
(2003;., . ;nfait et
al. )
( cutral
Tank-lie
\
y.i
U.86
0.43
24
251
504
30
1 liijh-
liiul
4fvl
3.4
1.68
4.7
64
128
Fab worker
DEVELOPMENTA
L EFFECTS
Increased Fetal
Resorptions
(2003; Saillenfait
al. 2002)
2lh
Central
Tendenc
y
2.6
0.26
0.14
83
820
1598
30
High-
End
67.7
4.5
2.20
3.2
48
98
Maintenance
DEVELOPMENTA
L EFFECTS
Increased Fetal
Resorptions
216
Central
Tendenc
y
10.1
0.95
0.47
21
228
458
30
High-
End
67.8
4.5
2.21
3.2
48
98
Page 241 of 487
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PEER REVIEW DRAFT, DO NOT CITE OR QUOTE
Acute Kxposur
i\ IVak
moi:
Acute
blood concent
ration
POD.
(nig/l.)
lien chili a r
('max
No
(llo\e
(llo\e
No
(llo\e
(llo\e
k moi:
1 lealtli KITect,
(ing/l.
Kxposu i'
glo\e
s PI
s PI
»lo\ e
s PI
s PI
(= Total
Kndpoint and Study
)
e l.e\el h
s
It)
20
s
It)
20
1 1 )
( 33; Saillenfait et
al. 2002)
Virgin NMP truck unloading
DEVELOPMENTA
Central
L EFFECTS
Tendenc
16.5
1.7
0.97
13
125
222
Increased Fetal
216
y
30
Resorptions
High-
End
(2003; Saillenfait et
al. 2002)
52.8
4.1
: in
4.1
52
103
Waste truck unloading
DEVELOPMENTA
Central
L EFFECTS
Tendenc
14.9
1.4
0.73
14
151
298
Increased Fetal
216
y
30
Resorptions
(2003; Saillenfait et
High-
End
47 4
3.7
1.82
4.6
59
119
al.. 2002)
11 MOEs < 30 are indicated in bold
b Central tendency means: central tendency (50thperce iink
truck loading, EPA scaled a single 8-hour TWA vali ic in a
¦i air concernralinn (for virgin NMP truck unloading and waste
4-lkuir 1 \\ \ \ allies). 1-hand dermal (445 cm2 surface area
exposed), and central tendcnc\ WIP ueidil fraction. Hmh-eiid means limli-eiid (95lh percentile) air concentration (for
virgin NMP truck unloading and u asie i ruck loading, EPA used a single 8-liour TWA value), 2-hand dermal (890 cm2
surface area exposed), and high-end uemlil WIP fraction.
5770
5771 MOEs calculated based dm high-end estimates of acute exposure to workers during NMP use in
5772 electronic parts manufacturing are below the benchmark MOE (30) in the absence of glove use. High
5773 end estimates of acute exposure to workers during NMP use in electronic parts manufacturing are above
5774 the benchmark MOI- with glo\ e use (IT 10). Although the MOE calculation incorporating a glove
5775 protection factor (PF 20) is above the benchmark MOE, EPA has not found information that would
5776 indicate speci lie activity training (e.g., procedure for glove removal and disposal) for tasks where
5777 dermal exposure can be expected to occur. The PF 20 glove protection factor is not assumed for any
5778 central tendency or hiuh-end estimates.
5779
Page 242 of 487
-------
PEER REVIEW DRAFT, DO NOT CITE OR QUOTE
Table 4-28. Non-Cancer Risk Estimates for Chronic Exposures Following Occupational Use of
Health K ITcd.
Kiiripoint and
Study
C 'h ron i
c POI).
,\rc
(hr
ing/i.)
Kxposur
e 1 .evel h
Chronic Kxposurc.
AlC (hr ni«/l.)
moi:
lien cli mar
k MOI.
(= Total
ri")
No
glo\e
s
(Jo\e
s PI
l()
(Jo\e
s PI
20
No
glo\e
s
(Jo\e
s PI
10
(Jo\e
s PI
20
Container hant
ling, small containers
REPRODUCTIV
E EFFECTS
Decreased
Fertility
(Exxon. 1991)
183
Central
Tendency
67.4
6.31
3.21
2.7
21)
57
30
High-End
444
31.8
15.71
0.4
5.S
12
Container handling, drums
REPRODUCTIV
E EFFECTS
Decreased
Fertility
(Exxon. 1991)
183
Central
Tendency
55.1
5 13
2.56
3.3
36
72
30
High-End
445
32.1
1
1.57
(i So
12
1 17
228
30
High-End
670
42 X
20^3
0.3
4.3
8.7
Maintenance
REPRODUCTIV
E EFFECTS
Decreased
Fertility
(Exxon. 1 )
IX i
Coin ml
1 ondoiios
M 1
5.65
2.81
3.0
32
65
30
1 liuh-l iid
<¦>71
42 w
21.04
0.3
4.3
8.7
Virgin NM1
' truck unloading
REPRODl CTIV
EEFI IX TS
Decreased
Fertility
(Exxon. 1 )
183
Com ml
Tendeno>
78.1
7.83
4.36
2.3
23
42
30
High-End
400
29.2
14.79
0.5
6.3
12.4
Waste truck unloading
REPRODUCTIV
E EFFECTS
Decreased
Fertility
(Exxon. 1991)
183
Central
Tendency
70.22
6.45
3.28
2.6
28
56
30
High-End
356
26.00
12.84
0.5
7.0
14.3
11 MOEs <30 indicated in bold
b Central tendency means: central tendency (50th percentile) air concentration (for virgin NMP truck unloading and waste
truck loading, EPA scaled a single 8-hour TWA value to a 4-hour TWA values), 1-hand dermal (445 cm2 surface area
exposed), and central tendency NMP weight fraction. High-end means high-end (95th percentile) air concentration (for
Page 243 of 487
-------
5782
5783
5784
5785
5786
5787
5788
5789
5790
5791
5792
5793
5794
5795
5796
5797
5798
5799
5800
PEER REVIEW DRAFT, DO NOT CITE OR QUOTE
Clironi
Chronic Exposure.
c POD.
AlC (lir mg/l.)
MOE
lien cli mar
Health KITect.
Al"C
No
(ilo\ 0
(i lo\ 0
No
(i lo\0
(il()\ 0
k MOE
Kntlpoint and
(lir
Exposur
»lo\e
s PI
s PI
<>lo\C
s PI
s PI
(= Total
Studv
ing/l.)
e 1 .e\ el h
s
It)
20
s
It)
20
IT)
\ irgm W1I' I ruck unloading and waste iinck loading, 1!!' \ used ;i single X-honr T\V \ \ alnej, 2-hand dermal (X'Ji) cm
surface area exposed), and high-end weight NMP fraction.
MOEs calculated based on high-end estimates of chronic exposure to workers during NMP use in
electronic parts manufacturing (i.e., handling, unloading, maintenance and fab worker) are below the
benchmark MOE (30) regardless of glove use. Although the MOE calculation incorporating a glove
protection factor (PF 20) is above the benchmark MOE, EPA has not found information that would
indicate specific activity training (e.g., procedure for glo\ c removal and disposal) lor tasks where
dermal exposure can be expected to occur. The PF 20 glo\ c protection factor is not assumed for any
central tendency or high-end estimates.
4.2.2.13 Soldering
Table 4-29. Non-Cancer Risk Estimates lor Acute Exposures l-'ollowing Occupational Use of NMP
in Soldering a
Acute Kxposure. Peak
Acute
hlood concent
ration
POD.
(m»/L)
MOK
lien chin a r
('max
No
(llo\e
No
(llo\e
k MOK
1 lealtli KITect,
(m»/L
Kxposur
»lo\e
(iloxe
s PI
»lo\ e
(iloxe
s PI
(= Total
Kndpoint iincl Studv
)
e l.e\el
s
s PI 5
10
s
s PI 5
10
1 1 )
DEVELOPMENTA
( cntml
L EFFECTS
TcikIciic
() 15
0 03
() 02
1436
7187
14376
Increased Fetal
\
30
Resorptions
1 liijh-
IjkI
^ 0 a cU t
aL 2)
(i i)7
0.19
0.10
222
1120
2242
a MOEs -.)() are indicated in bold
b Central lendencs means
: typical air concentration, 1-hand dermal (445 cm2 surface area exposed), and central tendency
NMP weight fraction 1 ligh-end means worst-case air concentration, 2-hand dermal (890 cm2 surface area exposed), and
high-end weight N\ll' I nchon.
The MOE calculated for NMP use in soldering based on high-end estimates of acute exposure is above
the benchmark MOE (30) in the absence of glove use (MOE = 222); the MOE calculated based on
central tendency estimates of acute exposure to workers during NMP use in soldering is above the
benchmark MOE with glove use (PF 5).
Page 244 of 487
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5801
5802
5803
5804
5805
5806
5807
5808
5809
5810
5811
5812
5813
5814
5815
5816
5817
5818
5819
5820
5821
5822
5823
5824
5825
5826
5827
5828
5829
5830
5831
5832
PEER REVIEW DRAFT, DO NOT CITE OR QUOTE
Table 4-30. Non-Cancer Risk Estimates for Chronic Exposures Following Occupational Use of
NMP in Soldering a
C 'h roil i
Chronic Exposure,
c POD.
Alt' (lir m»/l.)
MOE
lien chili a r
1 leallli EITecl,
Al C
No
(Jo\C
No
(i lo\c
u moi:
Kndpoinl ;iikI
(lir
Kxposnr
»lo\e
(Jo\C
S PI
«ilo\e
(ilo\ c
s PI
(= lolal
Sliulv
nig/I.)
el,e\el
s
s PI 5
10
s
s l»l 5
10
1 1 )
REPRODUCTIV
E EFFECTS
Central
Tendency
0.68
0.14
0.07
:7()
I35()
2701
Decreased
183
30
Fertility
(Exxon. 1991)
High-End
6.8
1.36
0.68
27
135
270
a MOEs <30 indicated in bold
b Central tendency means: typical air concentration, 1-hand dermal (445 air surface area exposed
). and central tendency
NMP weight fraction. High-end means worst-case air concentration. 2-hand dermal (890 cm2 surface area exposed), and
high-end weight NMP fraction.
The MOE calculated based on a high-end estimate of chronic exposure to workers from NMP use in
soldering is below the benchmark MOE (30) in the absence of glo\ e use (MOE = 27); the MOE
calculated based on a high-end estimate of chronic exposure to workers incorporating a glove protection
factor (PF 10) is above the benchmark MOE The MOI- calculated based on a central tendency estimate
of chronic exposure to workers with glove use (PI' 5) is above the benchmark MOE.
EPA considered the assessment approach, the quality of ilie data, and uncertainties to determine the
level of confidence
Primary Strengths
EPA assessed dermal exposure to central tendency and high-end NMP weight fractions, calculated as
the 50th and 95th percentiles, respecti\ ely. from the data provided by SIA (2019). which has a data
quality rating of high N\\ used directly applicable inhalation monitoring data, which is the highest of
the approach hierarchy, to estimate worker inhalation exposure during a variety of semiconductor
manufacturing tasks These data include over one hundred data points and have a data quality rating of
high.
Primary I iniiiaiions
The SIA ( ) monitoring data were provided as 8-hour or 12-hour TWA values. EPA assumed 8 or 12
hours as the high-end exposure duration and mid-range of 4 or 6 hours as the central tendency exposure
duration. The representati\ eness of the estimates of duration of inhalation and dermal exposure for the
assessed activities toward the true distribution of duration for all worker activities in this occupational
exposure scenario beyond semiconductor manufacturing is uncertain. Skin surface areas for actual
dermal contact are uncertain. EPA did not find data on the use of gloves for this occupational exposure
scenario and assumed glove usage is likely based on judgment. The assumed glove protection factor
values are highly uncertain. The majority of the data points in SIA (2019) were non-detect for NMP and,
for these samples, EPA used the LOD/2 to calculate central tendency and high-end inhalation exposure
concentration values. Due to the high amount of non-detect results, this method may result in bias. The
representativeness of the monitoring data for semiconductor manufacturing toward the true distribution
of inhalation concentrations for all worker activities in this occupational exposure scenario is uncertain.
Page 245 of 487
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5833
5834
5835
5836
5837
5838
5839
5840
5841
5842
5843
5844
5845
5846
5847
5848
5849
5850
5851
PEER REVIEW DRAFT, DO NOT CITE OR QUOTE
Overall Confidence
Considering the overall strengths and limitations, the overall confidence of the PBPK input parameters
for this occupational exposure scenario is medium. The studies that support the health concerns for
adverse developmental effects following acute exposure and adverse reproductive effects following
chronic exposure are described above in Section 3.2. Overall, EPA has high confidence in the health
endpoints and PODs selected for acute and chronic risk characterization. Section 3.2.6 describes the
justification for this confidence rating.
4.2.2.14 Fertilizer Application
Table 4-31. Non-Cancer Risk Estimates for Acute Exposures l-'ollowing Occupational Use of NMP
in Fertilizer Application a
1 lealtli KITect,
Kndpoint and Study
Acute
POD.
(max
(m»/l.
)
Kxposu i'
e l.e\el h
Acute Kxposure, Peak
blood concentration
moi:
lien chin a r
k moi:
(= Total
1 1 )
No
»lo\e
s
(llo\e
s PI 5
(llo\e
s PI
l()
No
»lo\ e
s
(llo\e
s l»l 5
(llo\e
s PI
l()
DEVELOPMENTA
L EFFECTS
Increased Fetal
Resorptions
(2003; Saillenfait et
al. 2002)
216
Central
Tendenc
y
() 15
() 14
0.13
1430
1587
1604
30
High-
End
2.9
0.70
04:
74
310
510
a MOEs < 30 are indicated mi hold
b Central tendency means: i\ pical air concentration, 1-hand dermal (445 cm2 surface area exposed), and central tendency
NMP weight fraction. High-end means u orst-case air concentration. 2-hand dermal (890 cm2 surface area exposed), and
high-end weight NMP fraction
The MOI-s calculated lor NMP use in fertilizer application based on high-end estimates of acute
exposure for workers arc al">o\ c the benchmark MOE (30) in the absence of glove use. Central tendency
and high-end estimates oraculc exposure to workers during the use of NMP in fertilizer application are
above the benchmark MOE with ulo\c use (PF 5).
Page 246 of 487
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5852
5853
5854
5855
5856
5857
5858
5859
5860
5861
5862
5863
5864
5865
5866
5867
5868
5869
5870
5871
5872
5873
5874
5875
5876
5877
5878
5879
5880
5881
5882
PEER REVIEW DRAFT, DO NOT CITE OR QUOTE
Table 4-32. Non-Cancer Risk Estimates for Chronic Exposures Following Occupational Use of
NMP in Fertilizer Application a
1 le.ilth K fleet,
Knilpoint itiul
Sliulv
Chroni
t I'OI).
Al C
(In-
mg/l.)
Kxposur
e l.e\el
Chronic Kxposure,
Al C (lir m«/l.)
moi:
lien chili ii r
k moi:
(= Tot sil
1 1 )
No
«ilo\e
s
(Jo\e
s l»l 5
(Jo\e
s l»l
It)
No
«ilo\e
s
(;io\c
s l»l 5
(;io\c
s l»l
1(1
REPRODUCTIV
E EFFECTS
Decreased
Fertility
(Exxon. 1991)
183
Central
Tendency
0.66
0.60
0.59
270
307
311
30
High-End
20.6
4.9
2.9
8.«>
38
62
aMOEs < 30 are indicated in bold
b Central tendency means: typical air concentration, 1-hand dermal (445 jir surface area c\posed). and central tendency
NMP weight fraction. High-end means worst-case air concentration. 2-haud dermal (890 cm' surface area exposed), and
high-end weight NMP fraction.
The MOE calculated for NMP use in fertilizer application based on a high-end estimate of chronic
exposure to workers is below the benchmark MOF, (30) in the absence of glove use (MOE = 9). The
MOEs calculated based on central tendency and high-end estimates of chronic exposure to workers
incorporating a glove protection factor (PF = 5) is aho\ e the benchmark MOE.
EPA considered the assessment approach, the quality of the data, and uncertainties to determine the
level of confidence
Primary Strengths
EPA assessed dermal exposure to <> I to 7'\. NMP, based on data from public comments and literature,
which have data quality ratings of high I-PA assessed occupational inhalation exposure during fertilizer
application using a modeled inhalation exposure concentration value, which is in the middle of the
approach hierarchy, from RIVM ( ). This data has a data quality rating of high.
Primary Limitations
EPA did not lind exposure duration data and assumed a high-end of 8 hours based on the length of a full
shift and a central tendency of 4 hours based on the mid-range of a shift. The representativeness of the
assumed estimates of duration of inhalation and dermal exposure toward the true distribution of duration
for all worker acli\ ities in this occupational exposure scenario is uncertain. Skin surface areas for actual
dermal contact are uncertain. EPA did not find data on the use of gloves for this occupational exposure
scenario and assumed glo\ e usage with minimal to no employee training or no glove usage due to the
commercial nature of this use. The assumed glove protection factor values are highly uncertain. The
modeled inhalation exposure concentration was obtained from RIVM (2013) and not generated by EPA.
The representativeness of the modeled exposure toward the true distribution of inhalation concentrations
for this occupational exposure scenario is uncertain.
Overall Confidence
Considering the overall strengths and limitations, the overall confidence of the PBPK input parameters
for this occupational exposure scenario is medium. The studies that support the health concerns for
Page 247 of 487
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5884
5885
5886
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5891
5892
5893
5894
5895
5896
5897
PEER REVIEW DRAFT, DO NOT CITE OR QUOTE
adverse developmental effects following acute exposure and adverse reproductive effects following
chronic exposure are described above in Section 3.2. Overall, EPA has high confidence in the health
endpoints and PODs selected for acute and chronic risk characterization. Section 3.2.6 describes the
justification for this confidence rating.
4.2.2.15 Wood Preservatives
Table 4-33. Non-Cancer Risk Estimates for Acute Exposures Following Occupational Use of NMP
in Wood Preservatives a
Health Effect, Eiulpoint
iiiul Stuilv
Acute
POD.
(max
Exposure
I.C\cl
Acute Exposure,
Peak blood
concentration
\
oi:
lien chin ark
MOE
(= Total
1 1 )
No
<>lo\cs
(ihnes
l»l 5
No
<>lo\cs
(Jo\cs
l»l 5
DEVELOPMENTAL
EFFECTS
Increased Fetal
Resorptions
(2003; Saillenfait et al..
2002)
216
Central
Tendency
0.34
n::
fv5
1 (ii
30
Hiuh-liikl
() 5 1
0.20
426
1099
a MOEs <30 indicated in bold
b Central tendency means: typical air concentration. 1 -hand dermal (445 cm surface area exposed), and central tendency
NMP weight fraction. High-end means u orsl-case air concern ration, 2-hand dermal (890 cm2 surface area exposed), and
high-end weight NMP fniclion
The MOE calculated based on a high-end estimate of acute exposure to workers from NMP use in wood
preservatives is above the benchmark \IOI- (3D) in the absence of glove use. The MOEs calculated
based on central tendency and high-end esli males of acute exposure to workers from NMP use in wood
preservatives are abo\ e the benchmark MOE (30) with glove use (PF 5).
Page 248 of 487
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5898
5899
5900
5901
5902
5903
5904
5905
5906
5907
5908
5909
5910
5911
5912
5913
5914
5915
5916
5917
5918
5919
5920
5921
5922
5923
5924
5925
5926
PEER REVIEW DRAFT, DO NOT CITE OR QUOTE
Table 4-34. Non-Cancer Risk Estimates for Chronic Exposures Following Occupational Use of
NMP in Wood Preservatives a
Health KITecl, Kndpoinl
and Studv
Chronic
l»()l).
Al C
(In
nig/I.)
Kxposure
I.C\cl ¦'
Chronic Kxposure,
Al C (lir m»/L)
\
oi:
lien ch in ark
moi:
(= lolal
1 1 )
No
«>lo\cs
(iloM'S
l»l 5
No
<>lo\ OS
(iloM'S
l»l 5
REPRODUCTIVE
EFFECTS
Decreased Fertility
(Exxc )
183
Central
Tendency
1.5
0.95
122
194
30
High-End
3.5
1.4
52
135
a MOEs < 30 are indicated in bold
b Central tendency means: typical air concentration, 1-hand dermal (445 cm: surface area exposed). and central tendency
NMP weight fraction. High-end means worst-case air concern nil ion. 2-hand dermal (89U cm surface area exposed), and
high-end weight NMP fraction.
The MOE calculated based on a high-end estimate of chronic exposure lo workers from NMP use in
wood preservatives is above the benchmark MOE (30) in the absence of glove use. MOEs for NMP use
in wood preservatives based on central tendency and high-end esli males of chronic exposure to workers
are above the benchmark MOE with glove use (PI 5)
EPA considered the assessment approach, the quality of llie data, and uncertainties to determine the
level of confidence.
Primary Strengths
EPA assessed dermal exposure lo I".. NMP. based on one wood preservative product identified in the
Use and Market Profile jor S-\ /ei/iy/pyrro/idone (Abt,: ). EPA assessed occupational inhalation
exposure during wood piesei \ ali\ e application using a modeled inhalation exposure concentration
value, which is in the middle of llie approach hierarchy, from RIVM (! ). This data has a data quality
rating of high.
Primary Limitations
EPA did not find exposure duration data and assumed a high-end of 8 hours based on the length of a full
shift and a central tendency of 4 hours based on the mid-range of a shift. The representativeness of the
assumed estimates of duration of inhalation and dermal exposure toward the true distribution of duration
for all worker activities in this occupational exposure scenario is uncertain. Skin surface areas for actual
dermal contact are uncertain. EPA did not find data on the use of gloves for this occupational exposure
scenario and assumed dove usage with minimal to no employee training or no glove usage due to the
commercial nature of this use. The assumed glove protection factor values are highly uncertain. The
modeled inhalation exposure concentration was obtained from RIVM (2013) and not generated by EPA.
The representativeness of the modeled exposure toward the true distribution of inhalation concentrations
for this occupational exposure scenario is uncertain.
Page 249 of 487
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5927
5928
5929
5930
5931
5932
5933
5934
5935
5936
5937
5938
5939
5940
5941
5942
5943
5944
5945
5946
5947
5948
PEER REVIEW DRAFT, DO NOT CITE OR QUOTE
Overall Confidence
Considering the overall strengths and limitations, the overall confidence of the PBPK input parameters
for this occupational exposure scenario is medium. The studies that support the health concerns for
adverse developmental effects following acute exposure and adverse reproductive effects following
chronic exposure are described above in Section 3.2. Overall, EPA has high confidence in the health
endpoints and PODs selected for acute and chronic risk characterization. Section 3.2.6 describes the
justification for this confidence rating.
4.2.2.16 Recycling and Disposal
Table 4-35. Non-Cancer Risk Estimates for Acute Exposures l-'ollowing Occupational Recycling
and Disposal of NMP a
1 lealtli K ITec I,
Kndpoint and Study
Acute
POD.
('max
(m»/l.
)
Kxposu i'
e I.cm'I h
Acute Kxposure, Peak
blood concentration
moi:
lien chin a r
k moi:
(= Total
1 1 )
No
»lo\e
s
(llo\e
s PI 5
(llo\e
s PI
l()
No
»lo\ e
s
(llo\e
s PI 5
(llo\e
s PI
l()
DEVELOPMENTA
L EFFECTS
Increased Fetal
Resorptions
(2003; Saillenfait et
al. 2002)
216
Central
Tendenc
y
3 S
0.76
0.38
283
562
30
High-
End
«)4
1 w
0.96
23
114
225
a MOEs < 30 are indicated mi hold
b Central tendency means: i\ pical air concentration, 1-hand dermal (445 cm2 surface area exposed), and central tendency
NMP weight fraction. High-end means u orst-case air concentration. 2-hand dermal (890 cm2 surface area exposed), and
high-end weight NMP fraction
The MOE calailalcd based on a hiuh-end estimate of acute exposure to workers from recycling and
disposal of NMP is below the benchmark MOE (30) in the absence of glove use; the MOE calculated
based on central tendency estimates of acute exposure to workers from recycling and disposal of NMP is
above the benchmark MOE in the absence of glove use. The MOE calculated based on a high-end
estimate of acute exposure lo workers from recycling and disposal of NMP is above the benchmark
MOE with glo\ e use (PI ' 5)
Table 4-36. >oil-Cancer Kisk Kslimates for Chronic Exposures Following Occupational Recycling
and Disposal of NMP "
Clironi
Chronic Kxposure.
moi:
c POD.
Al C (lir ni»/l.)
lien cli mar
Health K fleet.
Al C
No
(Ihnc
No
Chnc
k moi:
Kndpoinl and
(hi
Kxposur
«lo\e
Chnc
s PI
«ilo\e
Chnc
s PI
(= Total
Studv
m»/l.)
e Le\el
s
s PI 5
l()
s
s PI 5
10
I T)
REPRODUCTIV
E EFFECTS
183
Central
Tendency
7.9
1.57
0.79
23
116
232
30
Page 250 of 487
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5949
5950
5951
5952
5953
5954
5955
5956
5957
5958
5959
5960
5961
5962
5963
5964
5965
5966
5967
5968
5969
5970
5971
5972
5973
5974
5975
5976
5977
5978
5979
5980
5981
5982
5983
5984
5985
5986
5987
PEER REVIEW DRAFT, DO NOT CITE OR QUOTE
Decreased
Fertility
(Exxon. 1991)
High-End
21.6
4.2
2.14
8.5
43
86
11 MOEs < 30 are indicated in bold
b Central tendency means: typical air concentration, 1-hand dermal (445 cm2 surface area exposed), and central tendency
NMP weight fraction. High-end means worst-case air concentration, 2-hand dermal (890 cm2 surface area exposed), and
high-end weight NMP fraction.
MOEs calculated based on central tendency and high-end estimates of chronic exposure to workers from
recycling and disposal of NMP are below the benchmark MOE (30) in the absence of glove use. MOEs
calculated based on central tendency and high-end estimates of chronic exposure to workers from
recycling and disposal of NMP are above the benchmark MOE with glove use (PI' = 5).
EPA considered the assessment approach, the qualily of llie data, and uncertainties lo determine the
level of confidence.
Primary Strengths
Modeling, in the middle of the approach hierarchy, was used lo estimate occupational inhalation
exposure concentrations for both the unloading of NMP from bulk containers and from drums. For
modeling of these air concentrations, EPA attempted to address variability in input parameters by
estimating both central tendency and high-end parameter \ alues. Additionally, for modeling of air
concentrations during the unloading of drums. I -P A used Monte Carlo simulation to capture variability
in input parameters. EPA expects the duration of inhalation and dermal exposure to be realistic for the
unloading activities, as the durations are based on the length of time to unload NMP from specific
container sizes (i.e., tank trucks, rail cars, and drums).
Primary Limitations
The representativeness of the estimates of duration of inhalation and dermal exposure for the unloading
activities toward the true distribution of duration lor all worker activities in this occupational exposure
scenario is uncertain. EPA did not find NMP concentration data and assumed waste NMP may contain
very little impurities and he up to loo",, \MP. Skin surface areas for actual dermal contact are
uncertain F.PA did not find data on the use of gloves for this occupational exposure scenario and
assumed ulo\ e usage with basic employee training is likely based on judgment. The assumed glove
protection factor values are highly uncertain. For the modeling of NMP air concentrations, EPA is
uncertain of the accuracy of the emission factors used to estimate fugitive NMP emissions and thereby
estimate worker inhalation exposure concentration. The representativeness of the modeling results
toward the true distribution of inhalation concentrations for this occupational exposure scenario is
uncertain.
Overall Confidence
Considering the overall strengths and limitations, the overall confidence of the PBPK input parameters
for this occupational exposure scenario is medium. The studies that support the health concerns for
adverse developmental effects following acute exposure and adverse reproductive effects following
chronic exposure are described above in Section 3.2. Overall, EPA has high confidence in the health
endpoints and PODs selected for acute and chronic risk characterization. Section 3.2.6 describes the
justification for this confidence rating.
Page 251 of 487
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5988
5989
5990
5991
5992
5993
5994
5995
5996
5997
5998
5999
6000
6001
6002
6003
PEER REVIEW DRAFT, DO NOT CITE OR QUOTE
4.2.3 Risk Estimation for Exposures to NMP for Occupational Non-Users
The following table presents the risk estimates for chronic inhalation exposures to ONUs for
reproductive effects using estimated air concentrations from workplaces that use NMP in each OES.
ONUs are not assumed to be exposed via dermal contact with liquid NMP because they do not have
direct dermal contact with liquid chemicals, see section 2.4.1.1. ONUs are not assumed to be wearing a
respirator. Calculated MOE values that are below the benchmark MOE (30), indicate a risk concern
(shown in bold and shaded grey). Risk estimates for acute inhalation exposures to ONUs for
developmental effects in pregnant women from workplaces that use NMP are not shown because the
MOEs are all greater than the benchmark MOE of 30. The highest exposure scenario for ONUs is paint
removers - miscellaneous stripping with an 8 hr TWA air concentration of M mg/m3 and the peak blood
concentration is 1.53 mg/L and for the developmental effects with the POD peak blood concentration of
216 mg/L the MOE is 141, above the benchmark MOE of 30.
Table 4-37. ONU Risk Estimates based on Adverse Reproductive Effects (Decreased
Fertility) from Chronic NMP Exposures a
()ccup;ilion;il Exposure Sceiiiirio
.1
Exposure l.e\el
Chronic Exposure
Alt' (hr m»/l.)
MOEs'1
Manufacturing ui NiVlP
( enlral Tendency
i)()| 1
16344
High-Liul
0.3 1
587
Repackaging
Central Tendencx
i)()| 1
16344
High-End
0.31
587
Chemical Processing. Including
Formulation
Central Tendency
0.016
11255
High-End
0.055
3343
Incorporalion into formulation.
Mixture, or Reaelion Produel
( enlral Tendency
0.016
11255
1 [igh-End
2.63
70
Applicalion of Painls, Coalings.
Adhesives. and Sealants— Spray
Application
( entral Tendency
0.052
3525
High-End
0.93
197
Application of Painls. Coatings.
Adhesives, and Sealants—
Roll/curlain
Central Tendency
0.0059
30904
High-End
0.052
3522
Application of Paints, Coatings,
Adhesives, and Sealants—Dip
Central Tendency
0.19
944
High-End
0.57
321
Application of Paints, Coatings,
Adhesives, and Sealants—Brush
Central Tendency
0.81
226
High-End
0.85
215
Printing
Central Tendency
0.0017
108142
Page 252 of 487
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Occupiilioiiiil Kxposui c Scciiiirio
.1
Kxposuro I.cm'I
Chronic Kxposurc
Al (' (lir m«/l.)
MOKs'1
High-End
0.037
5001
Writing
Central Tendency
0.000032
5784391
High-End
0.00032
580007
Metal finishing - spray application
Central Tendency
ii ii53
3428
High-End
ii 14
195
Metal finishing - dip
Central Tendency
0 20
937
High-End
0 58
316
Metal finishing - brush
Central Tendency
0 81
High-End
0 86
213
Paint and coating removal - misc.
removal
Central Tendency
0 32
566
High-End
13
14
Paint and coating removal - graffiti
removal
Central Tendency
(i
920
High-I !nd
0
196
Dip cleaning
Central Tendency
0.20
934
High-End
0.58
314
Spray / Wipe Cleaning
Central Tendency
0.20
922
High-End
0.71
258
( ommeicial Automotive Servicing
Central Tendency
0.49
374
High-End
8.91
21
Laboratory Use
Central Tendency
0.010
17565
High-End
0.81
225
Electronic Parts \hiniilliclni iny—
Electronics (Small Container
Handling)
Central Tendency
0.15
1225
High-End
0.21
859
Electronic Parts Manufacturing-
Electronics (Container Handling,
Drums)
Central Tendency
0.0043
42649
High-End
0.50
368
Electronic Parts Manufacturing-
Electronics (Fab worker)
Central Tendency
0.041
4502
High-End
0.16
1137
Page 253 of 487
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PEER REVIEW DRAFT, DO NOT CITE OR QUOTE
Occupiilioiiiil Exposure Scciiiirio
.1
Exposure I.cm'I
Chronic Exposure
Al (' (lir m«/l.)
MOEs'1
Electronic Parts Manufacturing-
Electronics (Maintenance)
Central Tendency
0.0064
28624
High-End
0.25
739
Electronic Parts Manufacturing-
Electronics (Virgin NMP Truck
Unloading)
Central Tendency
0.94
195
High-End
(1 w
184
Section 2.4.1.2.12 - Electronic
Parts Manufacturing—Electronics
(Waste Truck Unloading)
Central Tendency
() 14
1313
High-End
() 17
1097
Soldering
Central Tcndeno
i) (i(i(i(i25
7224526
High-End
0.00063
28^802
Fertilizer Application
Central Tendencx
i) 58
315
High-End
1 1
171
Wood preservative
Central Tendency
0.81
226
1 IiliIi-I jid
0 84
219
Recycling and Disposal
Central Tendenc\
i)()| 1
16530
High-I jid
0.091
2007
aUse of PPE is not assumed for ONUs
b Central tendency means: typical air coiievulialinn for most scenarios. High-end means worst-case air concentration
for most scenarios. ONUs arc uni expected in ha\ c direct contact with NMP-containing liquids (see Section 2.4.1.1).
0 POD blood concentration = IS ^ nm'l.i \l ( )
d Benchmark MOE = 30: MOEs < "<> are indicated mi hold
6004
6005
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4.2.4 Risk Estimation for Acute Exposures from Consumer Use of NMP
The following sections present the risk estimates for acute dermal and inhalation exposures following
consumer use of NMP in each condition of use. Calculated MOE values that are below the benchmark
MOE (30), indicate a consumer safety concern (shown in red and bold)
4.2.4.1 Adhesives and Sealants
Table 4-38. Non-Cancer Risk Estimates for Acute Exposures Following Consumer Use of NMP in
Adhesives and Sealants
Kxposure
Scenario1
Health K ITccl.
Kndpoint and Study
POD (peak
hlood
concentration.
mg/L)
Women
childhearing
age Kxposure.
peak hlood
concentration.
Cmax (mg/l.)
moi:
Benchmark
MOE
( Total I I )
Sealants
Medium Intensity
Use
DEVELOPMENTAL
EFFECTS
Increased Fetal
Resorptions
(2003; Saillenfait et
2002)
210
0.011
19115
30
DEVELOPMENTAL
1111(IS
Increased Fetal
Resorptions
(2003; ^ .
)
Sealants
High Intensity Use
216
0.070
3086
30
Adhesi\ es
Medium Intensity
Use
DF\ F.LOI'MFN l .\l.
II 111 IS
Increased l-'elal
Resorptions
(2003. _ 1 ^
2002)
216
1.238
174
30
Adhesives
High Intensity Use
DEVELOPMENTAL
i:i 1 l-CTS
Increased Fetal
Resorptions
(2 . Saillenfait et aL
2002)
216
5.623
38
30
All MOEs calculated using a high-end estimate for acute exposure to consumers following use of NMP -
containing adhesives and sealants are above the benchmark MOE (30).
for these conditions of use.
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Overall Confidence
The adhesives scenarios and the sealants scenarios are based on corresponding publicly available
consumer product data, specifically the weight fractions and the amount of product used and duration of
use from consumer survey data. EPA has a high confidence in these parameters for representing the
adhesives and sealants consumer use scenarios.
EPA has a high confidence in the Consumer Exposure Model (CEM), its appropriate use for semi-
volatile chemicals such as NMP in estimating air concentrations based on the consumer use, activity
patterns, and NMP physical-chemical properties. The emission rate used in CEM for the adhesives
scenario and sealants scenario was estimated since product-specific emission from chamber studies was
not available. EPA has high confidence in the emission rate estimate based on physical-chemical
properties.
The input parameters for estimating the consumer's internal dose using the PBPk model are: the
estimated air concentration resulting from product use as predicted by CEM, the derma I contact time
(based on the duration of product use) and the weight fraction of the product.
EPA has a high confidence in the input parameters estimating the adhesi\ e scenario and the sealants
scenario.
The studies that support the health concerns lor ad\ erse developmental effects following acute exposure
and adverse reproductive effects following chronic exposure are described above in Section 3.2. Overall,
EPA has high confidence in the health endpoints and PODs selected for acute and chronic risk
characterization. Section 3.2.6 describes the justification for this confidence rating.
4.2.4.2 Adhesives Removers
Table 4-39. Non-Cancer Kisk Kslimates lor Acute Kxposures Following Consumer Use of NMP in
the Removal of At
hesives
Women
childhearing
POI) (peak
age Kxposure.
hlood
peak hlood
Benchmark
Kxposure
Health KITect.
conceni ration.
concent rat ion.
MOK
Scenario1
Kmlpoint and Study
nig/I.)
('max (nig/I.)
moi:
( Total I I )
DEVELOPMENTAL
EFFECTS
Medium Intensity
Increased Fetal
Use
Resorptions
(2003; Saillenfait et al..
2002")
216
1.292
167
30
DEVELOPMENTAL
High Intensity Use
EFFECTS
Increased Fetal
Resorptions
216
5.957
36
30
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6055
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6057
6058
6059
6060
6061
6062
6063
6064
6065
6066
6067
6068
6069
6070
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Kxposurc
Scenario1
llcnhli KITcd.
Kndpoinl mid Study
POD (pink
blood
concent ml ion.
mg/1.)
Women
childhcsiring
age Kxposurc.
peak blood
conccnlmlion.
Cnisix (nig/I.)
MOK
Kcnchmsirk
MOK
(Toliil I I )
(2003; Saillenfait et al„
2002)
All MOEs calculated using high-end estimates for acute exposure lo consumers from use of NMP -
containing adhesive removal products are above the benchmark MOE (30)
Overall Confidence
The adhesives remover scenario is based on corresponding publicly available consumer product data,
specifically the weight fractions and the amount of product used and duration of use from consumer
survey data. EPA has a high confidence in these parameters lor representing the adhesives remover
consumer use scenarios.
EPA has a high confidence in the Consumer F.xposure Model (CI AI). its appropriate use for semi-
volatile chemicals such as NMP in estimating air concentrations based on the consumer use, activity
patterns, and NMP physical-chemical properties The emission rate used in CEM for the adhesive
remover scenario was estimated since product-specific emission from chamber studies was not
available. EPA has high confidence in the emission rate estimate hased on physical-chemical properties.
The input parameters for estimating the consumer's internal dose using the PBPK model are: the
estimated air concentration resulting from product use as predicted by CEM, the dermal contact time
(based on the duration of product use) and the weight fraction of the product.
EPA has a high confidence in the input parameters estimating the adhesives remover scenario.
The studies that support Ihe health concerns for adverse developmental effects following acute exposure
and adverse reproductive effects following chronic exposure are described above in Section 3.2. Overall,
EPA has high confidence in the health endpoints and PODs selected for acute and chronic risk
characterization Section 3.2.0 describes the justification for this confidence rating.
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6085
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6087
6088
6089
6090
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Auto Interior Liquid and Spray Cleaners
Table 4-40. Non-Cancer Risk Estimates for Acute Exposures Following Consumer Use of NMP in
Auto Interior Liquid and Spray Cleaners
Kxposure
Scenario1
Health KITecl.
Kndpoint and Study
POD (peak
hlood
concentration.
mg/L)
W omen
childhcaring
age Kxposure.
peak hlood
concent rat ion.
('max (mg/l.)
moi:
Benchmark
MOE
( Total I I )
Auto Interior
Liquid Cleaner
Medium Intensity
Use
1)1 All.OPMI \ 1 \l.
EFFECTS
Increased Fetal
Resorptions
(2003; Saillenfait et aL,
2002)
:io
0.256
S44
30
Auto Interior
Liquid Cleaner
High Intensity Use
DEVELOPMENTAL
EFFECTS
Increased Fetal
Resorptions
(2003; Saillenfait et
2002")
216
4.355
50
30
Auto Interior Spray
Cleaner
Medium Intensity
Use
DEVELOPMENTAL
EFFECTS
Increased 1'elal
Resorptions
(2003. " "le
2002)
216
0.093
2323
30
Auto Interior Spray
Cleaner
High Intensity Use
DEVELOPMENTAL
1111(IS
Increased I'etal
Resorptions
(2003; ^
2002")
216
0.183
1180
30
All MOEs calculated using high-end estimates for acute exposure to consumers from the use of NMP-
containing auto interior (liquid and spray) cleaners are above the benchmark MOE (30).
Overall Confidence
The auto interior liquid cleaner scenario and the auto interior spray cleaner scenario are based on
corresponding publicly available consumer product data, specifically the weight fractions and the
amount of product used and duration of use from consumer cleaner/degreaser survey data. EPA has a
medium to high confidence in these parameters for representing the auto interior liquid cleaner scenario
and the auto interior spray cleaner consumer use scenarios.
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EPA has a high confidence in the Consumer Exposure Model (CEM), its appropriate use for semi-
volatile chemicals such as NMP in estimating air concentrations based on the consumer use, activity
patterns, and NMP physical-chemical properties. The emission rate used in CEM for the auto interior
liquid cleaner scenario and the auto interior spray cleaner scenario was estimated since product-specific
emission from chamber studies was not available. EPA has high confidence in the emission rate estimate
based on physical-chemical properties.
The input parameters for estimating the consumer's internal dose using the PBPK model are: the
estimated air concentration resulting from product use as predicted by CEM, the dermal contact time
(based on the duration of product use) and the weight fraction of the product.
EPA has a medium to high confidence in the input parameters estimating the aulo interior liquid cleaner
scenario and the auto interior spray cleaner scenario.
The studies that support the health concerns for adverse de\ elopmenlal effects following acute exposure
and adverse reproductive effects following chronic exposure are described above in Section 3 2. Overall,
EPA has high confidence in the health endpoints and PODs selected lor acute and chronic risk
characterization. Section 3.2.6 describes the justification lor this confidence rating.
4.2.4.4 Cleaners/Degreasers. Engine Cleaner/Degreaser and Spray Lubricant
Table 4-41. Non-Cancer Risk Estimates lor Acute Kxposures l-'ollowing Consumer Use of NMP in
Cleaners/Degreasers, Engine Cleaner/Degreaser and Spray Lubricant
Kxposure Scenario1
Health KITect.
Kndpoint and Study
POD (peak
blood
concenl ration.
nig/I.)
Women
childbcaring
age Kxposure.
peak blood
concent rat ion.
('max (mg/l.)
moi:
Benchmark
moi:
( Total I I )
di:\ 11opmi:\ r\i.
Cleaners Dcurcasers
Medium Intensity
Use
1 1 1 1(IS
Increased fetal
Resorptions
(2003, iqu wt
\_2002)
216
1.033
209
30
Cleaners/Degreasers
High Intensity Use
DEVELOPMENTAL
EFFECTS
Increased Fetal
Resorptions
C2;/J; Saillenfait et
al. 2002)
216
13.4D
16
30
Engine
Cleaner/Degreaser
Medium Intensity
Use
DEVELOPMENTAL
EFFECTS
Increased Fetal
Resorptions
216
1.682
128
30
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6124
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Kxposurc Sconsirio1
llcsihh KITocl.
Kndpoinl niul Study
POD (pcsik
blood
coiKTiilmlion.
mg/l.)
W OIlH'll
childlu'siring
:igo Kxposuro.
peak blood
coiKTiilmlion.
("insix (nig/I.)
moi:
ISencli 111:1 rk
moi:
(Tolsil I I )
(2003; Saillenfait et
al. 2002)
Engine
Cleaner/Degreaser
High Intensity Use
DEVELOPMENTAL
EFFECTS
Increased Fetal
Resorptions
(2003; Saillenfait et
al. 2002)
216
16.40
13
30
Spray Lubricant
Medium Intensity
Use
DEVELOPMENTAL
EFFECTS
Increased Fetal
Resorptions
(2003; Saillenfait
al.. 2002)
216
i) 332
651
30
Spray Lubricant
High Intensity Use
DEVELOPMENTAL
EFFECTS
Increased Fetal
Resoi plions
^ • if of
3C )
216
2.853
76
30
MOEs calculated based on hiuh end eslimales lor acute exposure to consumers from the use of NMP-
containinu cleaners dcurcascrs are below the benchmark MOE (30); MOE cieaners/degreaser = 16, MOE engine
cleaner/degreaser I J ).
Overall ('onjidence
The cleaner deureaser scenario and the engine cleaner/degreaser scenario are based on corresponding
publicly a\ ailable consumer product data, specifically the weight fractions and the amount of product
used and duration of use from consumer survey data. EPA has a high confidence in these parameters for
representing the cleaner deureaser and engine cleaner/degreaser consumer use scenarios.
EPA has a high confidence in the Consumer Exposure Model (CEM), its appropriate use for semi-
volatile chemicals such as NMP in estimating air concentrations based on the consumer use, activity
patterns, and NMP physical-chemical properties. The emission rate used in CEM for the
cleaner/degreaser scenario and engine cleaner/degreaser scenario was estimated since product-specific
Page 260 of 487
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emission from chamber studies was not available. EPA has high confidence in the emission rate estimate
based on physical-chemical properties.
The input parameters for estimating the consumer's internal dose using the PBPK model are: the
estimated air concentration resulting from product use as predicted by CEM, the dermal contact time
(based on the duration of product use) and the weight fraction of the product.
EPA has a high confidence in the input parameters estimating the cleaner deureaser scenario and the
sealants scenario.
The studies that support the health concerns for adverse developmental effects following acute exposure
and adverse reproductive effects following chronic exposure are described above in Section 3.2. Overall,
EPA has high confidence in the health endpoints and PODs selected for acute and chronic risk
characterization. Section 3.2.6 describes the justification lor this confidence rating.
4.2.4.5 Paints and Arts and Craft Paint
Table 4-42. Non-Cancer Risk Estimates for Acute Exposures h ollowing Consumer Use of NMP in
Paint and Arts anc
Craft Paint
Kxposure
Scenario1
Health Kfleet.
KihIpoint and Study
POD (peak
hlood
concentration.
mg/1.)
Women
childhearing
age Kxposure.
peak hlood
concentration,
('max (nig/l.)
moi:
Benchmark
MOE
( Total I I )
Paints
Medium Intensity
Use
di:\ i:i.op\ii:\t \i.
EFFECTS
Increased Fetal
Resorptions
(m;MllenfaitetaL
)
216
0.374
578
30
Paints
High Intensity L'sc
DEVJ IOPMFA I AF
EFFECTS
Increased Fetal
Resorptions
( T?: Saillenfait et al„
)
216
1.422
152
30
Arts and Crafts
Paints
Medium Intensity
Use
DEVELOPMENTAL
EFFECTS
Increased Fetal
Resorptions
(2003; Saillenfait et al..
2002)
216
0.071
3034
30
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Kxposure
Scenario1
Health K fleet.
KihIpoint and Slink
POD (peak
hloori
concent ration,
mg/l.)
Women
chilrihearing
age Kxposure.
peak hloori
concentration.
Cinax (mg/L)
moi:
Benchmark
MOK
( Total I I )
Arts and Crafts
Paints
High Intensity Use
DEVELOPMENTAL
EFFECTS
Increased Fetal
Resorptions
(2.003; Saillenfait et ai.
2002)
216
o 222
974
30
All MOEs calculated using high-end estimates of acute exposure to consumers from the use of NMP-
containing paints (including those used in arts and crafts) are above the benchmark MOI (3<)).
4.2.4.6 Stains, Varnishes, Finishes (Coatings)
Table 4-43. \on-Cancer Risk Estimates for Acute Exposures hollowing Consumer Use of NMP in
Stains. Varnishes. Kinishcs (Coalings)
Kxposure
Scenario1
Health Kfleet.
Knripoint and Study
POD (peak
hloori
concentration.
mg/L)
Women
childhcaring
age Kxposure.
peak hloori
concentration.
Cmax (mg/L)
moi:
Benchmark
MOK
( Total I I )
Medium Intensity
Use
di:\ i:i.oi>\ii:\t.\i.
EFI 1 ( I S
Increased I'etal
Resorptions
( . ; .s
2002)
216
0.341
633
30
High Intensity I se
DEVELOPMENTAL
fffects
Increased Fetal
Resorptions
( 003; Saillenfait et al..
2002)
216
1.947
111
30
All MOEs calculated using high-end estimates of acute exposure to consumers from the use of NMP-
containing stains, varnishes and finishes (coatings) are above the benchmark MOE (30).
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6159 4.2.4.7 Paint Removers
6160
6161 Table 4-44. Non-Cancer Risk Estimates for Acute Exposures Following Consumer Use of NMP in
6162 Paint Removers
Kxposure
Scenario1
Health K ITcd.
Kmlpoint and Study
POD (peak
hloori
concenl ration.
mg/L)
Women
chiklhcariiig
age Kxposure.
peak hloori
concent rat ion.
('max (nig/I.)
moi:
Benchmark
MOE
( Total I I )
Medium Intensity
Use
1)1 All.OPMI \ 1 \l.
EFFECTS
Increased Fetal
Resorptions
(2003; Saillenfait et aL,
2002)
210
2.02
107
30
High Intensity Use
DEVELOPMENTAL
EFFECTS
Increased Fetal
Resorptions
(2003; Saillenfait et
2002)
216
|l) 1)2
22
30
6163
6164 One MOE calculated using a high-end eslimale lor acute exposure lo consumers from the use of NMP-
6165 containing paint remo\ ers is helow the benchmark \IOI- (30), MOE High Intensity Use 22.
6166
6167
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4.2.4.8 Risks to Bystanders
Table 4-45. Risk Estimates to Adult Bystanders for Acute Exposures Following Consumer Use of
Kxposii re Seena rio1
lleahli 1 .fled.
Kndpoint and Study
POD (peak
hlood
concent rat ion.
ing/l.)
Women
childhearing
age Kxposure.
peak hlood
concent rat ion.
('max (mg/l.)
moi:
Benchmark
MOI.
( Total I I )
Cleaners/Degreasers
High-Intensity Use
DEVELOPMENTAL
EFFECTS
Increased Fetal
Resorptions
(2003; Saillenfait et
al. 2002)
:io
4.06
53
30
Engine
Cleaner/Degreaser
High Intensity Use
DEVELOPMENTAL
EFFECTS
Increased Fetal
Resorptions
(2003; Saillenfait et
al.. 2002)
:io
5.55
39
30
6172
6173
6174
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6175
6176
6177
Table 4-46. Risk Estimates for Adverse Developmental Effects (Increased Resorptions/Fetal
Mortality) from Acute Exposure to Bystanders via Consumer Use of NMP in Degreasing or
Kxposure Scenario1
Health K fleet.
K ml point and Sludy
POD (peak
hlood
concentration.
nig/I.)
Child (3-5\rs)
Kxposure.
peak hlood
concent rat ion.
('max (mg/l.)
moi:
Benchmark
MOE
(Total I I )
Cleaners/Degreasers
High-Intensity Use
DEVELOPMENTAL
EFFECTS
Increased Fetal
Resorptions
(2003; Saillenfait et
aL 2002)
:io
4.76
45
30
Engine
Cleaner/Degreaser
High Intensity Use
DEVELOPMENTAL
EFFECTS
Increased Fetal
Resorptions
(2003; Saillenfait
aL 2002)
216
6.51
33
30
6178
6179 All MOEs calculated using high-end estimates of acute exposure to bystanders from the use of NMP-
6180 containing degreasers or engine degreasers are al">o\ e the benchmark MOE (30).
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6190
6191
6192
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6196
6197
6198
6199
6200
6201
6202
6203
6204
6205
6206
6207
6208
6209
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6211
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4.3 Assumptions and Key Sources of Uncertainty
4.3.1 Assumptions and Uncertainties in Occupational Exposure Assessment
Assumptions and sources of uncertainty for occupational exposure estimates are described in greater
detail in Section 2.4.1.4. Sources of uncertainty and overall confidence in occupational exposure
estimates vary across occupational exposure scenarios. Overall confidence in exposure estimates for
specific conditions of use are described in Section 4.2.2.
A peer-reviewed PBPK model allows EPA to estimate aggregate exposures from simultaneous dermal
and inhalation and vapor-through-skin exposures with relatively high confidence The body weight
parameter is related to all of these three routes. The assumed values for human hody weight have
relatively lower uncertainties, and the median values used may underestimate exposures at the high-end
of PBPK exposure results.
Estimates of dermal exposure rely on a set of assumptions that introduce uncertainty because no data are
available for many parameters. The types of data and assumptions used to estimate exposure for each
exposure scenario is summarized in Table 4-48. Parameters thai rely on such assumptions include glove
use and effectiveness, durations of contact with liquid, skin surface areas for contact with liquids. For
many OESs, the high-end surface area assumption of contact o\ er the full area of two hands likely
overestimates exposures. EPA has more confidence in dermal exposure parameters that are supported by
data, such as NMP concentrations in formulas. There is also uncertainty around the impact of vapors
being trapped next to the skin during glove use. For most of the assumptions made for exposure
parameters and other sources of uncertainty, EPA does not have enough information to determine
whether most of these assumptions may overestimate or underestimate exposures. The NMP
concentrations in liquid used in dermal exposure predictions are likely to have a relatively low impact
(less than an order of magnitude, or factor of 10) on overestimation or underestimation of exposure.
Estimates of inhalation and \ apoi-lhrouuh-skin exposures also rely on various assumptions that
introduce uncertainty The specific types of data sources used Estimated air concentrations are based on
monitoring data where a\ ailable and based on deterministic or probabilistic modeling for exposure
scenarios lacking monitoring data. Table 4-47 summarizes the types of data used to estimate air
concentrations lor each occupational exposure scenario. The principal limitation of the air concentration
monitoring data is the uncertainty in the representativeness of the data. EPA identified a limited number
of exposure studies and data sets that provided data for facilities or job sites where NMP was used.
Some of these studies primarily focused on single sites. This small sample pool introduces uncertainty as
it is unclear how representative the data for a specific end use are for all sites and all workers across the
US. Limited monitoring datasets precluded EPA from describing actual parameter distributions. In most
scenarios where data were available, EPA did not find enough data to determine complete statistical
distributions to identify 50th and 95th percentile exposures. In the absence of percentile data for
monitoring, the means or midpoint of the range serve as substitutes for 50th percentiles of the actual
distributions and high ends of ranges serve as substitutes for 95th percentiles of the actual distributions.
The effects of limited air monitoring datasets of unknown representativeness on the occupational
exposure assessment are unknown. They may result in either over or underestimation of exposures
depending on the actual distribution.
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Where air monitoring data were not available, exposure was estimated based on deterministic or
probabilistic modeling. Modeling approaches used to estimate air concentrations also have uncertainties.
Parameter values used in models did not all have distributions known to represent the modeled scenario.
It is also uncertain whether the model equations generate results that represent actual workplace air
concentrations. Some activity-based modeling does not account for exposures from other activities.
Additional model-specific uncertainties are included below. In general, the effects of model-specific
uncertainties on the exposure estimates are unknown, as the uncertainties may result in either over or
underestimation on exposures depending on the actual distributions of each of the model input
parameters.
Table 4-47. Summary of Occupational Air Concentration Estimate Approaches
Kxposurc Scenario
Work Activity
Worker
Personal
Breathing
/one
Monitoring
Data
Modeling:
Deterministic
Worker 11
Modeling:
Probabilistic
Worker (\)
Near Field/
OM Far
Field (\ ' )
Potential
OM -related
Data
1. Manufacturing
Loading NMP
into bulk
containers
X
Loading NMP
into drums
\
2. Repackaging
Unloading WIP
from bulk
containers
X
Unloading WIP
from drums
X
3. Chemical
Processing.
Excluding
Formukilion
I nloading NMP
from drums
X
4. Incorporation inlo
Formulation,
Mixture, or
Reaction Product
Unloading liquid
\ MP from drums
X
Maintenance,
bottling,
shipping, loading
X (7 samples)
A(area
monitoring) c
5. Metal finishing
Spray application
X (26 samples)
A(area
monitoring) c
Dip application
X (138
samples)
Xb
Brush application
xb
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Kxposnre Scenario
Work Activity
Worker
Person ;il
lirenthiii"
/one
Monitoring
l);il si
Modeling:
Deterministic
Worker"
Modeling:
Probabilistic
Worker (\)
Nesir l-'ield/
OM l-'sir
l-'ield (\ ' )
Potent inl
OM -relsited
6. Removal of
Paints, Coatings,
Adhesives and
Sealants
Miscellaneous
paint, coating,
adhesive, and
sealant removal
X (unknown) d
Graffiti removal
X (25 samples)
Spray application
X (26 samples)
X(area
monitoring) c
7. Application of
Paints, Coatings,
Adhesives and
Sealants
Roll/ curtain
application
X
Dip application
X (138
samples)
X b
Roller/ brush and
syringe/ bead
application
X b
Container
handling (small
containers).
X (14 samples)
Container
handling, drums
\ (11) samples)
8. Electronic Paris
Manul'aclurmij
1 ¦"iih worker
\ (28 samples)
A(area
monitoring) c
Maintenance
X (36 samples)
Virgin NMP
truck unloading
X (1 sample)
Waste truck
loading
X (1 sample)
9. Printing and
Printing
X (48 samples)
Writing
Writing
Inhalation not assessed
10. Soldering
Soldering
Inhalation not assessed
11. Commercial
Automotive
Servicing
Xe
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Kxposure Scenario
Work Activity
Worker
Personal
Breathing
/one
Monitoring
Data
Modeling:
Deterministic
Worker"
Modeling:
Probabilistic
Worker (\)
Near l-'ield/
OM lar
Field (\ ' )
Potential
OM -related
Data
12. Laboratory Use
Laboratory use
X (1 sample)
X b
13. Cleaning
Dip cleaning /
degreasing
X (138
samples)
X'1
Spray / wipe
cleaning
X (105
samples)
X'1
14. Fertilizer
application
Spray application
X b
15. Wood
preservatives
Brush application
X'1
16. Recycling and
disposal
Unloading NMP
from bulk
containers
X
Unloading NMP
from drums
X
a - The deterministic modeling approaches estimate worker exposures.
b - These modeling estimates are from liieniiure i t v'ivl. 2- ; ¦). Other modeling estimates are from modeling performed by
EPA.
c - While area monitoring data were identified. there is some uncertainly about the representativeness of these data for ONU
exposures for these specific exposure scenarios because of the intended sample population and the selection of the specific
monitoring location.
d - The number of samples is unknown. The data source onl\ presented the range.
e - This modeling includes Near Field modeling for w orker exposures and Far Field modeling for ONU exposures. Far Field
modeling results are not included in the RF but arc included in Risk Evaluation for N-Methylpyrrolidone (2-Pyrrolidinone, 1
Methyl-) (NMP), Supplemental Information on Occupational Exposure Assessment (U.S. EPA. 2019r).
Table 4-48. Summary of W orker Dermal Parameter Estimate Approaches
Kxposure Scenario
Work Activity
NMP weight
Traction in the
liquid product
Total skin
surface area of
hands in contact
with the liquid
product1'
Duration of
dermal
contact with
the liquid
product'
1. Manufacturing
Loading NMP
into bulk
containers
Data (2016 CDRa)
Default
Assumption
Activity-
based
Assumption
Loading NMP
into drums
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Kxposure Scenario
Work Activity
NMP weight
fmction in the
liquid product
1 otiil skin
suiTsice siresi of
lisinds in contsict
with the liquid
product1'
Duriition of
dermsil
conflict with
the liquid
product'
2. Repackaging
Unloading NMP
from bulk
containers
Data (2016 CDRa)
Default
Assumption
Activity-
based
Assumption
Unloading NMP
from drums
3. Chemical
Processing,
Excluding
Formulation
Unloading NMP
from drums
Data (2016 CDRa,
public comments,
and Use and Market
Profile for N-
Methylpyrrol i done'1)
Default
Assumption
Activity-
based
Assumption
4. Incorporation into
Formulation,
Mixture, or
Reaction Product
Unloading liquid
NMP from drums
Data (2016 CDRa,
public comments,
literature, and Use
and Market Profile
for N-
Methylpy noli done'1)
Default
Assumption
Activity-
based
Assumption
Maintenance,
bottling, shipping,
loading
Default
Assumption
5. Metal finishing
Spray application
Data (2012 and
2016 CDRa)
Default
Assumption
Default
Assumption
Dip application
IJi'iish application
6. Rcmo\ al of
Painls. Coalings,
Adhesivcs and
Sealants
Miscellaneous
paiill. coaling.
adhesi\e. and
sealant removal
1 )ata (public
comments,
literature, and Use
and Market Profile
for N-
Methylpyrrolidonea)
Default
Assumption
Activity-
based
Assumption
(central
tendency)and
Default
Assumption
(high-end)
(iraflili removal
Default
Assumption
7. Application of
Paints, Coatings,
Adhesives and
Sealants
Spray application
Data (public
comments,
literature, and Use
and Market Profile
Default
Assumption
Default
Assumption
Roll/ curtain
application
Dip application
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Kxposure Scenario
Work Activity
NMP weight
fVnction in the
liquid product
1 otiil skin
suiTsice siresi of
lisuids in contsict
with the liquid
product1'
Duriition of
dermsil
conflict with
the liquid
product'
Roller/ brush and
syringe/ bead
application
for N-
Methylpyrrolidonea)
8. Electronic Parts
Manufacturing
Container
handling (small
containers);
Data (SIAa, public
comments,
literature, and I [se
and Market Prolile
for N-
Methylpyrrolidonc1)
Default
Assumption
Default
Assumption
Container
handling, drums
Fab worker
Maintenance
Virgin NMP truck
unloading
Waste truck
loading
9. Printing and
Writing
Priming
Data (public
comments, and Use
and Market Profile
lor \-
Melhylpvrrolidonea)
Del an ll
Assumption
Default
Assumption
Writing
Data (Australian
Government
Department of
Health (: ))
Non-default
Assumption
10. SoklcniiiJ
Soldering
Data (Use and
Market Profile for
N-
Methylpyrrolidonea)
Default
Assumption
Default
Assumption
11. Commercial
Automotive
Servicing
Data (public
comments and the
Use and Market
Profile for N-
Methylpyrrolidonea)
Default
Assumption
Activity-
based
Assumption
(central
tendency)and
Default
Assumption
(high-end)
12. Laboratory Use
Laboratory use
Non-default
Assumption
Default
Assumption
Activity-
based
Assumption
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Exposure Scenario
Work Activity
NMP weight
Traction in the
liquid product
Total skin
suiTacc area of
hands in contact
with the liquid
product1'
Duration of
dermal
contact with
the liquid
product'
(central
tendency)and
Default
Assumption
(high-end)
13. Cleaning
Dip cleaning /
degreasing
Spray / wipe
cleaning
Data (public
comments,
literature sources,
and the Use and
Market Profile for
N-
Methylpyrrol i done'1)
Default
Assumption
Default
Assumption
14. Fertilizer
application
Spray application
Data (literature,
puMic comments,
and the I se and
Market Profile for
N-
Methyl pyrrol i done3)
Default
Assumption
Default
Assumption
15. Wood
preservatives
lirush application
Data (Use and
Market Profile for
\-
Methyl pyrrol idonea)
Default
Assumption
Default
Assumption
16. Rcc\clniij and
disposal
I nloadinu WIP
from hulk
containers
Unloading NMP
from drums
Data (SIAa) and
Non-default
Assumption
Default
Assumption
Default
Assumption
6250 a - Sources for w ciulil fractions: 2016 CDR (U.S. EPA. 2017c'). Use and Market Profile for N-Methylpyrrolidone (Abt.
6251 20.1.7'). 2012 CDR (U.S. EPA, 20.12b), SIA (2019). as well as various public comments and literature sources.
6252 b - Default assumption for "Total skin surface area of hands in contact with the liquid product" is: (1) high-end value, which
6253 represents two full hands in annuel with a liquid: 890 cm2 (mean for females), 1070 cm2 (mean for males); (2) central
6254 tendency value, which is half of two full hands (equivalent to one full hand) in contact with a liquid and represents only the
6255 palm-side of both hands exposed to a liquid: 445 cm2 (females), 535 (males).
6256 c - Default assumption for "Duration of dermal contact with the liquid product" is: (1) high-end value of a full-shift, usually
6257 8 or 12 hours; central tendency value of value of half of a full-shift, usually 4 or 6 hours.
6258
6259 4.3.2 Data Uncertainties in Consumer Exposure Assessment
6260 Systematic review was conducted to identify chemical- and product-specific monitoring and use data for
6261 assessing consumer exposures. As no product-specific monitoring data were identified, exposure
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scenarios were assessed using a modeling approach that requires the input of various chemical
parameters and exposure factors. When possible, default model input parameters were modified based
on chemical and product specific inputs available in literature and product databases. Uncertainties
related to these inputs are discussed below.
4.3.2.1 Product & Market Profile
The products and articles assessed in this risk evaluation are largely based on EPA's 2016-2017 Use and
Market Profile for N-methyl-2-pyrrolidone, which provides information on commercial and consumer
products available in the US marketplace at that time (Abt., ). While it is possible that some
products may have changed since 2017, EPA believes that the timeframe is recent enough to still
represent the current market. Information on products from the Use and Market Profile was augmented
with other sources such as the NIH Household Product Survey and EPA's Chemical and Products
Database (CPDat), as well as available product labels and safety data sheets (SI)Ss) However, it is still
possible that the entire universe of products may not have been identified, due to market changes or
research limitations.
4.3.2.2 Westat Survey
A number of product labels and/or technical fact sheets were identified for use in assessing consumer
exposure. The identified information often did not contain product-specific use data, and/or represented
only a small fraction of the product brands containing the chemical of i nterest. A comprehensive survey
of consumer use patterns in the United States, called the Household Solvent Product: A National Usage
Survey ( 7), was used to parameterize critical consumer modeling inputs, based on
applicable product and use categories. This large sui \ e\ of o\ er 4,920 completed questionnaires,
obtained through a randomized sampling technique, is highly relevant because the primary purpose was
to provide statistics on the use of sol\ ent-containing consumer products for the calculation of exposure
estimates. The survey focused oil 32 different common household product categories, generally
associated with cleaning, painting. IuItrieating, and automotive care. Although there is uncertainty due to
the age of the use pattern data, as specific products in the household product categories have likely
changed over time, EPA assumes that the use pattern data presented in the Westat survey reflect
reasonable estimates for current use patterns of similar product type. The Westat study aimed to answer
he following key questions for each product category, some of which were used as key model inputs in
his consumer assessment
room of product use (key input environment of use),
how much time was spent using the product (key input: duration of product use per event),
how much of the product was used (key input: mass of product used per event),
how often the products were used,
when the product was last used,
product form ul a t i o n.
brand names used, and
degree of ventilation or other protective measures undertaken during product use.
The strengths and weakness of the Westat survey are discussed in more detail below with an emphasis
on the key modeling inputs.
Product Use Category
A crosswalk was completed to assign consumer products in the current risk evaluation to one of the
product or article scenarios in the CEM model, and then to an appropriate Westat survey category.
Although detailed product descriptions were not provided in the Westat survey, a list of product brands
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and formulation type in each category was useful in pairing the Westat product categories to the
scenarios being assessed. In most cases, the product categories in the Westat survey aligned well with
the products being evaluated. For product scenarios without an obvious Westat scenario match,
professional judgment was used to make an assignment. For a limited number of scenarios, technical
fact sheets or labels with information on product use amounts were available, and this information was
used in the assessment as needed.
Another limitation of the Westat data is that while the overall respondent size of the survey was large,
the number of users in each product category was varied, with some product categories having a much
smaller pool of respondents than others. Product categories such as spot remo\ ers, cleaning fluids, glues
and adhesives, lubricants, paints, wood stains, engine degreasers, and specialized electronic cleaners had
sample sizes ranging from roughly 500 to 2,000 users; whereas, categories such as shoe polish, adhesive
removers, rust removers, and brake cleaners had sample sizes of less than 50o users
The survey was conducted for adults ages 18 and older. Most consumer products are targeted to this age
category, and thus the respondent answers reflect the most representative age group. I lo\\e\ er, youth
may also be direct users of some consumer products. It is unknown how the usage patterns compare
between adult and youth users, but it is assumed that the product use patterns for adults will be very
similar to, or more conservative (i.e., longer use duration, higher frequency of use) than use patterns for
youth.
Room of Use
The CEM model requires specification of a room of use. which results in the following default model
assumptions (relevant for inhalation exposure only), ventilation rales, room volume, and the amount of
time per day that a person resides in the room of use. The Westat survey provided the location of
product use for the following room categories: basement, living room, other inside room, garage, and
outside. The room with the highest percentage was selected as the room to model in CEM. For some
specific product scenarios, how e\ er. professional judgement was used to assign the room of use; these
selections are documented abo\ e in Table 2-72 of Section 2.4.2.4. For many scenarios in which "other
inside room" was the highest percentage, the utility room was selected as the default room of use. The
utility room is a smaller room, and therefore may provide a more conservative assumption for peak
concentrations. In cases w here outside was identified as the "room of use," but it was deemed reasonable
to assume the product could be used inside (such as for auto care products), the garage was typically
selected as the room of use.
Amount of Product I Tscd and I titration of Product Use
The Westat survey reported the number of ounces per use, derived from the fluid ounces of product used
per year (based on can size and number of cans used), divided by the number of reported uses per year.
The duration of use (in minutes) reported in Westat was a direct survey question. An advantage to these
parameters is that the results are reported in percentile rankings and were used to develop profiles of
high intensity, moderate intensity, and low intensity users of the products (95th, 50th, and 10th
percentile values, respectively). In cases where a product was not crosswalked to a CEM scenario, the
amount of product used was tailored to those specific products instead of depending on Westat data.
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Ventilation and Protection
For most scenarios, the CEM model was run using median air exchange rates from EPA's Exposure
Factors Handbook ( ), and interzone ventilation rates derived from the air exchange rates and the
default median building volume from EPA's Exposure Factors Handbook (2011). These inputs do not
incorporate any measures that would serve to increase air exchange. The Westat survey questions
indicated that most respondents did not have an exhaust fan on when using these products, most
respondents kept the door to the room open when using these products, and most people reported
reading the directions on the label. The modeling conducted by EPA did not account for specific product
instructions or warning labels. For example, some product labels might indicate that protective
equipment (chemical resistant gloves or respirator) should be worn, which would lower estimated
exposures
4.3.2.3 Other Parameters and Data Sources
Activity Patterns
EPA assumed that a consumer product would be used only once per day. This is a realistic assumption
for most scenarios, but a high-intensity user could use the same product multiple times in one day.
Additionally, CEM allows for selection of activity patterns based on a "stay-at-home" resident or a part-
time or full-time "out-of-the home" resident. The activity patterns were developed based on
Consolidated Human Activity Database (CHAD) data of aciiv ity patterns, which is an EPA database that
includes more than 54,000 individual study days of detailed human behavior. It was assumed that the
user followed a "stay-at-home" activity pattern that would place them in various rooms as well as
outside of the home and room of use for more time than a part-time or full-time "out-of-the home"
resident. Therefore, applying an "out-of-the home" resident acti\ ity pattern would reduce estimated
exposures.
Product Density
If available, product-specific densities were obtained from SDS information, and used to convert the
ounces of the product used from Wcslal. to grams of product used. If product-specific densities were not
available, default product densities from the (TAI I ser Guide were used.
Outdoor Scenario
The CEM model does not currently accommodate outdoor scenarios. For products that are solely
intended to he used outdoors, modifications to the CEM inputs were made to simulate an outdoor
scenario hy adjusting Zone 1 parameters (which represents the room of use, or outside). The garage was
selected as the room of use, but the room volume was changed to 16 m3 to represent a half dome
chemical cloud around the person using the product. Additionally, the air exchange rate for Zone 1 was
set to 100 to reflect the high rate between the cloud and the rest of outside. The interzone ventilation rate
was set to 0, which elTecti\ ely blocks the exchange of air between Zone 1 and the rest of the house.
Thus, the concentrations users are exposed to inside the home after product use is zero. In the outside
scenario, non-users are assumed to have zero exposures. These assumptions may be either an
underestimate of exposures given outdoor conditions such as high temperatures in summer which could
increase volatilization of NMP in the product but could also be an overestimate of exposures if outdoor
conditions could include wind that effectively disperses the NMP in air.
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4.3.3 Approach and Methodology for Uncertainties in Consumer Exposure Assessment
EPA's approach recognizes the need to include an uncertainty analysis. An important distinction for
such an analysis concerns variability versus uncertainty - both aspects need to be addressed. Variability
refers to the inherent heterogeneity or diversity of data in an assessment. It is "a quantitative description
of the range or spread of a set of values" and is often expressed through statistical metrics, such as
variance or standard deviation, that reflect the underlying variability of the data. Uncertainty refers to a
lack of data or an incomplete understanding of the context of the risk assessment decision.
Variability cannot be reduced, but it can be better characterized. Uncertainty can be reduced by
collecting more or better data. Quantitative methods to address uncertainty include non-probabilistic
approaches such as sensitivity analysis and probabilistic methods such as Monte Carlo analysis.
Uncertainty can also be addressed qualitatively, by including a discussion of factors such as data gaps
and subjective decisions or instances where professional judgment was used
4.3.3.1 Deterministic vs. Stochastic Approaches
With deterministic approaches, the output of the model is fully determined by the choices of parameter
values and initial conditions. Stochastic approaches feature inherent randomness, such that a given set of
parameter values and initial conditions can lead to an ensemble of different model outputs. Because
EPA's largely deterministic approach involves choices regarding low. medium, and high values for
highly influential factors such as chemical mass and frequency duration of product use, it likely captures
the range of potential exposure levels although it does not necessarily enable characterization of the full
probabilistic distribution of all possible outcomes
4.3.3.2 Sensitive Inputs
Certain inputs to which model outputs are sensitive, such as zone \ olumes and airflow rates, were not
varied across product-use scenarios As a result, model outcomes for extreme circumstances such as a
relatively large chemical mass in a relatively low-volume environment likely are not represented among
the model outcomes. Such extreme outcomes are believed to lie near the upper end (e.g., at or above the
90th percentile) of the exposure distribution
4.3.4 Knvironmenlal Hazard and Exposure Assumptions Uncertainties
In the NMP Problem Formulation ( 2018c) and this RE, EPA completed a screening level
evaluation of en\ ironmental risk using inherently conservative assumptions. The analysis was completed
using "high-end" estimated concentrations of NMP in the aquatic environment as described in Section
2.3.2 and compared those acute and chronic exposure estimates to conservative measures of acute and
chronic hazard (concentrations of concern) as described in Section 3.1.2. EPA in the NMP Problem
Formulation (U K - ) did not conduct any further analyses on pathways of exposure for
terrestrial receptors as described in Section 2.5.3.1 of the NMP Problem Formulation and further
described in Section 2.2 and 2.3 of this RE.
4.3.5 Human Health Hazard Assumptions and Uncertainties
There is a robust dataset for the critical reproductive and developmental effects that serve as the basis
for the points of departure used in this risk characterization. High quality studies have consistently
documented the developmental effects of NMP exposure across species and following dermal, oral, and
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inhalation exposures. The high quality of studies, consistency of effects, relevance of effects for human
health, coherence of the spectrum of reproductive and developmental effects observed and biological
plausibility of the observed effects of NMP contribute to the overall confidence in the PODs identified
based on reproductive and developmental endpoints.
Data on the reproductive and developmental toxicity of NMP in humans are not available. Therefore,
this risk evaluation relies on the assumption that reproductive and developmental toxicity observed in
animal models is relevant to human health. It is unknown whether this assumption contributes to an
overestimate or underestimate of risk.
The rat PBPK model used to derive PODs based on internal doses facilitates integration of dose-
response information from multiple high-quality studies that assessed the effects of NMP exposure
across multiple routes. This model incorporates toxicokinetic information, reducing a key source of
uncertainty in animal-to-human extrapolation. Furthermore, the availability of this model in combination
with studies directly evaluating developmental toxicity across multiple exposure routes eliminates the
need for route-to-route extrapolation thereby eliminating another source of uncertainty.
There are several remaining sources of uncertainty around the identification of PODs. As discussed in
Section 3.2.1, there is uncertainty associated with the reproducti\ e endpoints selected as the basis for the
POD used to evaluate risks from chronic NMP exposure. Because NMP exposures occurred throughout
development and into adulthood in the key study, it is not known which pcriod(s) of exposure
contributed to the reduced fertility seen in adult rats It is also unclear u liich life stages may be most
sensitive to the adverse reproductive effects of NMP exposure in humans. Although effects on male
fertility and female fecundity were not consistently observed across studies, the POD derived from the
key study is within close range of PODs derived from developmental endpoints that are consistently
observed across studies, species, and routes of exposure. It is unknown whether the limited set of 2-
generation studies contributed to an o\ erestimate or underestimate of risk. The concordance of PODs
across reproductive and developmental endpoints and consistency of developmental effects across
species and exposure routes contributes to the o\ ei ill I confidence in the POD.
In developmental toxicity studies, there is inherent uncertainty around the potential contribution of
maternal toxicity to ohser\ ed developmental effects. The maternal effect reported in the Saillenfait
(200.0 inhalation study (transient decrease in body weight gain and food consumption) has been cited as
a confounding factor by some study authors. EPA does not concur with this assertion, specifically as it
relates to the obsei \ ed decrease in maternal body weight gain on GD 6-21 (minus gravid uterine
weight). Although a decrease in maternal body weight gain was observed, it is not statistically
significant. Dams weighed roughly 235 g at GD 0, and whereas the controls gained approximately 32
grams, the high dose dams gained slightly less, roughly 26 grams. Given the lack of significant change
in maternal body weight gain, it is unlikely that the observed decreases in fetal and pup body weights
reflect a secondary effect of maternal toxicity. In other key and supporting studies, including an
inhalation study (Solomon et at '' I <\ipomt De Nemours & Co. 1990). and an oral gavage study
(Saillenfait et ai. 2002). similar decreases in pup body weight were observed at similar exposure levels,
in the absence of any effects on maternal body weight. These findings support EPA's conclusion that
this developmental effect is a direct consequence of NMP exposure.
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In addition, because the partial pressure of NMP depends on the temperature and relative humidity of
the test system, variations in test protocol can introduce uncertainty regarding the actual exposure
concentrations achieved in some of the inhalation studies used for hazard characterization. The PODs
that were ultimately selected did not rely on studies with this source of uncertainty, making it unlikely
that this uncertainty contributes to an overall over or under-estimate of risk.
Another important source of uncertainty around POD selection is the lack of complete information on
potentially sensitive reproductive and developmental endpoints. Though the database for developmental
toxicity is robust, some endpoints have not been fully characterized. For example, as described in
Section 3.2.3.1, there is evidence of neurodevelopmental effects following gestational exposure to a
relatively high dose of NMP, but a NOAEL for neurodevelopmental endpoints has not been identified.
Incomplete information on potentially sensitive endpoints could lead to an underestimate of risk.
Overall, EPA has high confidence in the acute and chronic PODs identified for e\ illuming risk from
NMP. The PODs are derived from endpoints that fall along a continuum of reproducti\ e and
developmental effects that are consistently observed in response to NMP across oral, dermal and
inhalation exposure routes. Application of the PBPK model reduces uncertainties associated with
extrapolation across species and exposure routes, further contributing to overall confidence in the PODs.
4.3.6 Risk Characterization Assumptions and Uncertainties
This risk characterization uses peer-reviewed luinuin unci nil IMiPK models for NMP to make a direct
comparison of internal doses (blood concentrn lions) predicted in humans in specific exposure scenarios
to internal concentrations that occurred in rats in toxicology studies The human PBPK models allows
EPA to estimate total human exposures from combined inhalation and dermal exposures associated with
specific exposure scenarios. The rut PIJPK model facilitates integration of data from studies using
different routes of exposure. Both models incorporate information on toxicokinetics, providing more
robust exposure estimates and reducing uncertainties about species differences.
The peer-re\ iewed luinuin PBPK models for NMP allow EPA to estimate total human exposures from
combined inhalation and dermal exposures associated with specific exposure scenarios. The relative
exposures from dermal, inhalation and \ apor through skin can be deduced by comparing the internal
exposure to workers due to inhalation, \ apor through skin and dermal liquid contact with internal
exposure to OM s due to inhalation and vapor through skin exposure (a subtraction technique). The
chronic exposures to workers assume no glove use and ONUs and calculated percent exposure due to
dermal contact with liquid are shown in Table 4-50.
Table 4-49. Comparison of NMP Exposures by Route Showing Percent Exposure Due to Dermal
Contact with Liquid from Chronic NMP Exposures a
Occiip;ition;il Kxposnre
Scenario''
KxpOSIII'C I.C\cl
Chronic
Kxposnrc
Worker'. AI C
(lir m»/l.)
No »lo\CS
Chronic
Kxposnrc OM
Al C (lir
m»/l.)
Percent
Kxposnrc Due
to Derniiil
Contiict with
Liquid'
Manufacturing of NMP
Central Tendency
8.6
0.011
100%
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()cciip;ilion;il Kxposuro
Scoiiiirio •'
K\|)()SIIIV I.CM'I
Chronic
Kxposuiv
Worker'. AI (
(lir m»/l.)
No <>lo\es
Chronic
Kxposurc OM
A1 C (lir
ni»/l.)
I'lTcenl
Kxposuiv Duo
to Dcrniiil
C'onlncl with
Liquid'
High-End
81.4
0.31
100%
Repackaging
Central Tendency
8.6
0.011
100%
High-End
81.4
i) 31
100%
Chemical Processing, Excluding
Formulation
Central Tendency
6.2
0.016
100%
High-End
12.7
ii ii55
100%
Incorporation into Formulation,
Mixture, or Reaction Product
Central Tendency
<\2
O.OlO
100%
High-End
4O3.0
2.63
99%
Application of Paints, Coatings,
Adhesives, and Sealants-
Spray Application
Central Tendency
1.41
0.052
96%
High-End
I7w h
0.93
99%
Application of Paints. Coatings.
Adhesives, and Sealants—
Roll/curtain
Central Tendency
1.36
100%
High-End
I7S 4
0.052
100%
Application of Paints. Coatings.
Adhesives, and Sealants—Dip
Central Tendency
1 55
0.19
88%
11 il: h-End
179.1
0.57
100%
Application of Paints. Coatings.
Adhesives, and Sealants—Brush
( enlml Tendency
2.18
0.81
63%
11 il: h-End
179.5
0.85
100%
Printing
Ccnlral Tendenc\
3.4
0.0017
100%
1 ligh-End
19.5
0.037
100%
\\ nling
( enlml Tendency
0.0016
0.000032
98%
High-End
0.0032
0.00032
90%
Metal finishing - s|na>
applicalion
Central Tendency
44
0.053
100%
High-End
347
0.94
100%
Metal finishing - dip
Central Tendency
44
0.20
100%
High-End
346
0.58
100%
Metal finishing - brush
Central Tendency
45
0.81
98%
High-End
347
0.86
100%
Central Tendency
5.55
0.32
94%
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()cciip;ilion;il Lxposuro
Scoiiiirio •'
K\|)()SIIIV I.CM'I
Chronic
Lxposuiv
Worker'. AI (
(lir m»/L)
No <>lo\es
Chronic
Lxposurc OM
Al ( (lir
m»/L)
I'lTcenl
Kxposuiv Duo
to Dcrniiil
C'onlncl with
Liquid'
Paint and coating removal -
misc. removal
High-End
268
13
95%
Paint and coating removal -
graffiti removal
Central Tendency
36.3
() 20
99%
High-End
212
() 93
100%
Dip cleaning
Central Tendency
64.0
(i 20
100%
High-End
399
0 58
100%
Spray / Wipe Cleaning
Central Tendency
22.3
0.20
99%
High-End
3l>3
0.71
100%
Commercial Automotive
Servicing
Central Tendency
0
0.49
47%
High-End
113
8.91
92%
Laboratory Use
Central Tendency
36
() mo
100%
High-End
4(1(1
0.81
100%
Electronic Parts Manufacturing-
Electronics (Small Container
Handling)
Central Tendency
ft7 4
0.15
100%
1 Iigh-End
444
0.21
100%
Electronic Parts Manufacturing—
Electronics (Container Handling,
Drums)
Central Tendency
55.1
0.0043
100%
1 Iigh-Hnd
445
0.50
100%
Electronic Parts Manulacluring—
Electronics (Fab worker)
Central Tendency
15.6
0.041
100%
11 il: h-End
670
0.16
100%
Electronic Pails Manufacturinu—
Eleclronics (Maintenance)
Ceil I ml Tendency
61.1
0.0064
100%
High-End
671
0.25
100%
Electronic Paris Manufacturing—
Electronics (Virgin WIP Truck
Unloading)
Central Tendency
78.1
0.94
99%
High-End
400
0.99
100%
Section 2.4.1.2.12 - Electronic
Parts Manufacturing-
Electronics (Waste Truck
Unloading)
Central Tendency
70.22
0.14
100%
High-End
356
0.17
100%
Soldering
Central Tendency
0.68
0.000025
100%
High-End
6.8
0.00063
100%
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()cciip;ilion;il Kxposuro
Scoiiiirio •'
K\|)()SIIIV I.CM'I
Chronic
Kxposuiv
Worker'. AI C
(lir m»/l.)
No <>lo\es
Chronic
Kxposurc OM
Al C (lir
m»/l.)
I'crccnl
Kxposuiv Duo
lo Dcrniiil
Conine! wilh
Liquid'
Fertilizer Application
Central Tendency
0.66
0.58
11%
High-End
20.6
1.1
95%
Wood preservative
Central Tendency
1.5
n SI
46%
High-End
3.5
() 84
76%
Recycling and Disposal
Central Tendency
7.9
() <)| 1
100%
High-End
21.6
O.oyj
100%
aUse of PPE is not assumed for ONUs
Percent due to dermal liquid exposure is the worker exposure (inlialalion. vapor through skin and dermal liquid contact)
minus ONU exposure (inhalation and vapor through skin exposure) di\ ided by worker exposure
b Central tendency means: typical air concentration for most scenarios 1 hull-end means worst-case air concentration for
most scenarios. ONUs are not expected to have direct contact wilh NMI'-auilaining liquids (see Section 2.4.1.1). These
exposure scenarios do not assume glove use.
0 See tables of exposure estimates in Section 4.2.2
d See tables of exposure estimates in Section 4.2.3
e Due to rounding 100% is shown when the inhalation and \ apor ihroimh skin exposures arc small relative to dermal liquid
contact however inhalation and vapor through skin exposures are noi zero, see llie exposure estimates and MOEs
calculation in Section 4.2.3
Uncertainty factors used lo generate benchmark MOEs used in the risk characterization account for
various sources of uncertainly lor each non-cancer POD. In this evaluation, benchmark MOEs for all
scenarios are consistently low. relleclinu the relatively low degree of overall uncertainty. As described
in detail in Section 3.2.5.4. there are two uncertainly factors used in this risk characterization across all
exposure scenarios:
• An interspecies uncertainty \ ariability factor of 3 (UFa) was applied for animal-to-human
extrapolation to account for loxicodynamic differences between species. Toxicokinetic
differences are incorporated into PBPK models.
• A default intraspecies uncertainty/variability factor (UFh) of 10 was applied to account for
variation in sensiti\ ity within human populations, including variation across gender, age, health
status, or genetic makeup.
The human populations considered in this draft risk evaluation include pregnant women and men and
women of reproductive age in occupational and consumer settings. Although exposures to younger non-
users may be possible, there is insufficient data regarding specific genetic and/or life stage differences
that could impact NMP metabolism and toxicity for further refinement of quantitative risk estimates.
EPA does not have sufficient information to determine whether these uncertainty factors may lead to an
overestimate or underestimate of risk.
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4.4 Potentially Exposed or Susceptible Subpopulations
TSCA § 6(b)(4) requires that EPA conduct a risk evaluation to "determine whether a chemical
substance presents an unreasonable risk of injury to health or the environment, without consideration of
cost or other non-risk factors, including an unreasonable risk to a potentially exposed or susceptible
subpopulation identified as relevant to the risk evaluation by the Administrator, under the conditions of
use " TSCA § 3(12) states that "the term 'potentially exposed or susceptible subpopulation' means a
group of individuals within the general population identified by the Administrator who, due to either
greater susceptibility or greater exposure, may be at greater risk than the general population of adverse
health effects from exposure to a chemical substance or mixture, such as mjanis. children, pregnant
women, workers, or the elderly
As described in Section 3.2.5.2, certain biological characteristics may increase susceptibility to NMP
exposure. The developmental effects identified as a critical human health endpoini lor acute exposures
in this draft risk evaluation are a major concern for pregnant women, the developing fetus, and women
who may become pregnant. The reproductive effects identified as a critical human health endpoint for
chronic exposures may be of concern for all adults of reproductive age as well as for children and
adolescents whose reproductive systems are still developing Other populations that may be more
sensitive to the hazards of NMP exposure include people with pre-exi sting conditions, and people with
lower metabolic capacity due to life stage, genetic \ ariation. or impaired liver function. The magnitude
of the effect of each of these factors alone or in combination on o\erall risk is unknown.
The acute and chronic PODs used in this risk characterization are hased on studies that evaluated effects
of exposure during sensitive life stages in rats. Toxicology data ( , idemonstrate early
postnatal body weight decreases and early postnatal death at doses that are greater than the POD derived
for decreased fertility from the same study It is considered likely that these postnatal outcomes are the
result of repeated exposures to NMP These fi tidings could be considered a surrogate for analysis of
risks to newborns and young infants
There is insufficient information to support a quantitative analysis of interindividual variability in other
potentially susceptible populations. An uncertainty factor of 10 was applied to account for uncertainty
related to interindividual \ aiiahility, but the actual effect of various factors contributing to biological
susceptibility on overall risk is unknown
As described in Section 2.5.1, EPA identified workers, occupational non-users, consumers of NMP-
containing products and bystanders, including children, as potentially exposed populations. The
exposure factors and hazard endpoints used in this draft risk evaluation are representative of the most
sensitive subpopulations (i e., pregnant women or women who might become pregnant, male workers,
and the fetus). The associated risk findings are expected to be protective of children and adolescents. In
developing the risk evaluation, the EPA analyzed the reasonably available information to ascertain
whether some human receptor groups may have greater exposure than the general population to the
hazard posed by a chemical. For example, EPA estimated acute exposures for children who may be
located near the consumer user at the time of use and determined that these exposures were below levels
that may pose a risk.
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4.5 Aggregate and Sentinel Exposures
Section 2605(b)(4)(F)(ii) of TSCA requires the EPA, as a part of the risk evaluation, to describe whether
aggregate or sentinel exposures under the conditions of use were considered and the basis for their
consideration. The EPA has defined aggregate exposure as "the combined exposures to an individual
from a single chemical substance across multiple routes and across multiple pathways (40 CFR §
702.33)."
In many exposure scenarios, NMP exposure occurs through multiple routes. Considering risk from a
single exposure route at a time instead of evaluating total exposures could underestimate risk. This risk
characterization therefore relies on exposure estimates that account for multiple simultaneous routes of
exposure to NMP. Exposure for each condition of use was evaluated by determining both the exposure
to NMP vapor and dermal contact with the liquid. Time profiles of each type of exposure were estimated
for a variety of job categories and household consumer uses, behaviors, and activity profiles. Vapor
exposure is specified by the air concentration encountered as a function of time during the work-day or
for 24 h from the start of a household application. Dermal contact is characterized by the weight fraction
(WF) of NMP in the product being used, the surface area of skin (hands) exposed, and the duration of
the dermal exposure. For workplace exposures vapor and dermal exposures are assumed to be only
simultaneous (both end at the end of the task, shift, or work day) I'or household exposures vapor
exposure typically continues for some time after the application is complete due to slower air exchange
but is lower for the rest of house than the location u here the project is done, with movement of the
individual between these zones included. Dermal exposure for consumers is also limited to the user's
direct contact with the product as defined by the duration of use
The PBPK exposure model was used to integrate absorption from both vapor and liquid contact via three
pathways: inhalation of v apors, absorption of liquid in contact with the skin, and absorption of vapor by
exposed skin. Exhalation and desorption of vapor from skin are also post-exposure elimination
pathways. Vapor absorption through the skin is a minor component of total exposure in most scenarios
but is included for completeness and uses the same dermal resistance as liquid absorption to account for
absorption from un-occluded areas of the face, neck, arms and hands. Use of a face mask is assumed to
reduce concentration inside the mask In a factor of 10 (i.e., the mask has a protection factor, PF = 10)
while use of gloves is assumed to reduce the surface area of the skin exposed to liquid NMP, where the
PF was \ aried for different quality glo\ es
While this assessment evaluates specific COUs based on exposure estimates that incorporate multiple
routes of exposure, it does not consider the potential for aggregate exposures from multiple conditions of
use. For example, it does not evaluate the aggregate risk to individuals exposed via occupational and
consumer uses. This could result in an underestimate of risk.
EPA defines sentinel exposure as "the exposure to a single chemical substance that represents the
plausible upper bound of exposure relative to all other exposures within a broad category of similar or
related exposures (40 CFR § 702.33)." In this risk evaluation, EPA considered sentinel exposure in the
form of high-end estimates for consumer and occupational exposure scenarios which incorporate dermal
and inhalation exposure, as these routes are expected to present the highest exposure potential based on
details provided for the manufacturing, processing and use scenarios discussed in Section 2.4. The
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exposure calculation used to estimate dermal exposure to liquid is conservative for high-end
occupational and consumer scenarios where it assumes full contact of both hands and no glove use.
4.6 Risk Conclusions
4.6.1 Environmental Risk Conclusions
No risks to fish, aquatic invertebrates or algae were identified from NMP releases to ambient water.
EPA used environmental release data from EPA's Toxics Release Inventory (TRI) and a "first-tier"
exposure assessment to derive conservative estimates of NMP surface water concentrations near
facilities reporting the highest NMP water releases. Using the 2015 TRI data and RPA's Exposure and
Fate Assessment Screening Tool (EFAST, Version 2014) EPA predicted NMP surface water
concentrations as high as 224 |ig/L and 1,496 |ig/L for the acute and chronic exposure scenarios,
respectively. Based on this analysis the acute and chronic RQs are 0.0022 and 0.S5, respectively
indicating a low concern for risks to aquatic organisms from NMP exposures via surface water.
4.6.2 Human Health Risk Conclusions
In general, the conditions of use that present the lowest concern for human health risks include those that
incorporate a high level of containment or small-scale use of NMP. The conditions of use which involve
a lower level of containment, elevated temperatures or high intensity use show greater risk even when
personal protective equipment is considered. For example, high-end occupational exposure estimates for
NMP use in cleaning, metal finishing, electronic parts manufacturing, automotive servicing, and use in
(or removal of) paints, coatings, adhesives and sealants show risks that are not mitigated via glove use.
For consumers, risk concerns are indicated for acute exposures associated with high-intensity use of
paint removers, degreasers and engine degreasers (see Table 4-51). The main factors that impact
consumer exposures during use of W IP-containing products include the NMP weight fraction, duration
of product use and the actual amount of product used (see Table 2-79 and Table 2-85). In addition,
specific factors related to the room of use (e.g., room size, air exchange rate) may affect the estimated
NMP air concentrations to w liich consumers may be exposed. For example, air concentrations can vary
depending on w hether window s or garage doors are open or closed during product use. Variations in
individual acti\ ity patterns can also impact exposure potential (e.g., risks associated with the engine
degreasing acti\ ity may be underestimated if the product is used continuously). Bystander exposures
were estimated for conditions of use that presented risks to the product user; these exposure scenarios
did not present a risk concern to bystanders located outside the room of product use.
EPA has high confidence in the hazard endpoints used to evaluate risks associated with acute and
chronic NMP exposure. As discussed in Section 3.2.6, fetal resorptions (mortality) and reduced fertility
were considered relevant hazards for evaluating risks following acute and chronic NMP exposure,
respectively. While there is some uncertainty regarding temporal windows of vulnerability for
developmental toxicity and whether the timing of a single exposure can produce a permanent adverse
effect on human development, EPA considers the developmental toxicity endpoints associated with
NMP exposure to be applicable to acute exposures. The available literature suggests that a single
developmental exposure may have sustained effects on the conceptus. Fetal mortality represents the
most severe endpoint associated with the developmental hazard profile for NMP. Reduced fertility in
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6678 males is the most sensitive effect associated with chronic exposures. The chronic POD based on effects
6679 on reduced male fertility is supported by effects on female fecundity and developmental toxicity in a
6680 similar dose range.
6681
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6682
Mil- ( } I'll' Sl;l«>i-/ ( ;lli-c;ik-<>»rk
I.\|>omiiv Si-i-n;irio
Poituhilion
r.\|)(isuri'
l.l'M'l
Risk r.slim.il
.Willi-
\oil-i';mi'iT
(hi'iii'li m;i I'k
MOI. = 30)
is lor \o ITI.
Chronii-
Ndll-l'illll'lT
(l>iiii-hni;irk
MOI. = 30)
Risk Llsiini;
.Willi-
Non-i'imi'i-r
(l>i-ni'hni;irk
MOI! = 30)
li-s \>ilh I'lM".
Chronic
Ndii-i'iini'i-r
(Iti-ni'hniiirk
MOI. = 30)
Mam lib cli ire/Dome stic
manufacture
Domestic Manufacture
Section 2.4.1.2.1 -
Manufacturing
Worker
Central
Tendenev
52
21
1025
(PI- 20)
423
(PF 20)
High-
End
<).<)
2.2
194
(PF 20)
48
(PF 20)
ONTJ
Central
Tendency
16,344
N/A
N/A
High-
End
-
587
N/A
N/A
Manufacture/Import
Import
Section 2.4.1.2.2 -
Repackaging
Winker
Central
Tendency
52
21
518
(PF 10)
213
(PF 10)
High-
End
<).<)
2.2
101
(PF 10)
25
(PI 10)
ONrT
Central
Tendency
-
16,344
N/A
N/A
High-
End
-
587
N/A
N/A
Processing/Processing as a
reactant or intermediate
Intermediate in plastic material and resin and
pharmaceutical and medicine manufacturing
Section 2.4.1.2.3 -
Chemical Processing,
1 Excluding Formulation
Worker
( entral
Tendency
62
2')
612
(PF 10)
291
(PF 10)
Oilier
High-
End
31
14
301(PF 10)
143
(PF 10)
ONU
Central
Tendency
-
11,255
N/A
N/A
High-
End
-
3,343
N/A
N/A
Processing/Incorporated
into formulation, mixture or
reaction product
Adhesives and sealant chemicals in Adhesive
Manufacturing
Section 2.4.1.2.4 -
Incorporation into
Formulation. Mixture,
or Reaction Product
Worker
Central
Tendenev
62
2<)
612
(PF10)
291(PF 10)
Anti-adhesive agents in Printing and Related
Support Activities
High-
End
4.1
0.5
49
(PF 10)
(>
(PI 10)
Paint additives and coating additives not
described by other codes in Paint and
Coating Manufacturing: and Print Ink
Manufaelurinc
Central
ONU „ ,
1endency
11,255
N/A
N/A
High-
End
70
N/A
N/A
Processing aids not otherwise listed in Plastic
Material and Resin Manufacturing
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Mil- ( } I'll' Sl;l«>i-/ ( ';lli-c;ik-<>»rk
I.\|>omiiv Si'i-n.irio
Poituhilion
r.\i>oMiiv
l.l'M'l
Risk r.slim;ll
.Willi-
(l>i-ni'hm;irk
MOI. = 30)
is lor \o ITI.
(Iironk-
\oll-l'illH'lT
(Iti-ni'hm.irk
MOI. = 30)
Risk Llsiini;
.Willi-
\on-i';mi'iT
(Iti-ni-h iii;i rk
MOI. = 30)
li-s \>iih I'l'L".
Chronic
Noll-l'Wll'lT
(l>i'iii'hin:irk
M()i: = 30)
Manufacturing; Primary Metal
Manufacturing; Soap, Cleaning Compound
and Toilet Preparation Manufacturing;
Transportation Equipment Manufacturing;
All Other Chemical Preparation
Manufacturing; Printing and Related Support
Activities; Services; Wholesale and Retail
Trade Product and
Surface active agents in Soap, Cleaning
Compound and Toilet Preparation
Manufacturing
Plating agents and surface treating agents in
Fabricated Metal Product Manufacturing
Solvents (which become part of product
formulation or mixture) in Electrical
Equipment, Appliance and Component
Manufacturing; Other Manufacturing; Paint
and Coating Manufacturing; Print Ink
Manufacturing; Soap, Cleaning Compound
and Toilet Preparation Manufacturing:
Transportation Equipment Manufacturing:
All Other Chemical Product and Preparation
Manufacturing; Printing and Related Support
Activities; Wholesale and Retail Trade
Other uses in Oil and Gas I )rilling.
Extraction and Support Activities: Plastic
Material and Resin Manufaclurine: Services
Processing/Incorporated
into article
Lubricants and lubricant additives in
Machinery Manufacturing
Section 2.4.1.2.5 -
Metal Finishing
(Spray Application)
Worker
Central
Tendencv
23
4.2
235
(PF 10)
44
(1'1; 10)
High-
End
4.7
0.5
58
(PF 10)
7
(PI 10)
ONU
Central
Tendency
-
3,428
N/A
N/A
High-
End
-
195
N/A
N/A
Page 287 of 487
-------
PEER REVIEW DRAFT, DO NOT CITE OR QUOTE
Mil- ( } I'll' Sl;l«>i-/ ( ;lli-»n
l.\|>osun- Si'i-n.irio
Po|>ul;ilion
r.vpoMuv
l.l'M'l
Risk r.slim;ll
.Willi'
(l>i-ni'hm;irk
MOI. = 30)
is lor \o PPI.
Chronic
Noii-csiih'it
(Itiiii'liiiiiirk
MOI. = 30)
Risk Llsiini;
.Willi-
\on-i';mi'iT
(l)iiii-hin;irk
MOI. = 30)
li-s \>ilh PIT.
Chronii-
N(in-i';mi'i'r
(l)i'iii-hni;irk
M()i: = 30)
Paint additives and coating additives not
described by other codes in Transportation
Equipment Manufacturing
Section 2.4.1.2.7 -
Application of Paints,
Coatings, Adhesives,
and Sealants
(Spray Application)
Worker
Central
Tendency
690
130
5152
(PF 10)
976
(PF 10)
High-
End
8.7
1.0
97
(PF 10)
12
(PI 10)
nxr
Central
Tendency
3,525
N/A
N/A
High-
End
-
197
N/A
N/A
Section 2.4.1.2.7 -
Application of Paints.
Coatings, Adhesives,
and Sealants
(Roll/Curtain)
Winker
Central
Tendencv
714
134
6880
(PF 10)
1294
(PF 10)
TTigh-
I ind
S.S
1.0
103
(PF10)
12
(PI 10)
ONU
Central
Tendency
-
30,904
N/A
N/A
High-
End
-
3,522
N/A
N/A
Section 2.4.1.2.7-
Application of Paints,
('oatings, Adhesives,
and Sealants
(Dip)
Worker
( entral
Tendency
623
118
2,092
(PF 10)
556
(PF 10)
High-
End
S.S
1.0
99
(PF 10)
12
(PI 10)
ONU
Central
Tendency
-
944
N/A
N/A
High-
End
-
321
N/A
N/A
Section 2.4.1.2.7 -
Application of Paints,
Coatings, Adhesives,
and Sealants
(Brush)
Worker
Central
Tendency
440
84
1003
(PF 10)
194
(PF 10)
High-
End
8.7
1.0
97
(PF 10)
12
(PI 10)
ONU
Central
Tendency
-
226
N/A
N/A
High-
End
-
215
N/A
N/A
Solvents (which become part of product
formulation or mixture), including in
Textiles, Apparel and I .eather Manufacturing
Section 2.4.1.2.4 -
Incorporation into
Formulation, Mixture,
or Reaction Product
Worker
Central
Tendency
62
2<)
612 (PF 10)
291
(PF 10)
High-
End
4.1
0.5
49
(PF 10)
6
(PI 10)
™,-n-T Central
ONU „ ,
1endency
-
11,255
N/A
N/A
Page 288 of 487
-------
PEER REVIEW DRAFT, DO NOT CITE OR QUOTE
Mil- ( } I'll' Sialic/ ( all-«>on
Sul>c;ik-<>»rk
I.\|>omiiv Si'i-nario
Poituhilion
r.\|)(isuri'
l.l'M'l
Risk r.slim;ll
.Willi-
Non-i-ani'i-r
(l>i-ni'hmark
MOI. = 30)
is lor No ITI.
(lironk-
Non-eani'i'i'
(Iteni-hniark
MOI. = 30)
Risk Llsiini;
.Willi-
\oil-i';mi'iT
(Itiiii-hmark
MOI. = 30)
les \>iih PIT.
Chronic
Non-i'ani'i-r
(Iti'iii'hmark
M()i: = 30)
High-
End
-
70
N/A
N/A
Other, including in Plastic Product
Manufacturing
Section 2.4.1.2.3 -
Chemical Processing,
Excluding Formulation
Worker
Central
Tendency
62
29
612
(PF 10)
291 (PF 10)
High-
End
31
14
301 (PF 10)
143(PF 10)
()Nl J
Central
T endency
11.255
N/A
N/A
High-
End
-
3.343
N/A
N/A
Processing/Recycling
Recycling
Section 2.4.1.2.16 -
Recycling and Disposal
Winker
Central
Tendencv
56
23
282
(PF 5)
116
(PF5)
I Iigh-
I ind
23
S.5
114
(PF5)
43
(PF 5)
ONI J
Central
Tendency
-
16,530
N/A
N/A
High-
End
-
2,007
N/A
N/A
Processing/Repackaging
Wholesale and Retail Trade
Section 2.4.1.2.2-
Repackaging
Worker
( entral
Tendency
52
21
518(PF 10)
213
(PF 10)
High-
End
<).<)
2.2
101 (PF 10)
25
(IT 10)
ONU
Central
Tendency
-
16,344
N/A
N/A
High-
End
-
587
N/A
N/A
Distribution in Commerce/
Distribution
Distribution in commerce
Distribution in
commerce
„ j , Central
Worker _ ,
1endency
Not separately addressed
Industrial, commercial, and
consumer use/Paint and
coatings
Paint and coating removers
Adhesive removers
Section 2.4.1.2.6 -
Removal of Paints,
Coatings, Adhesives,
and Sealants
(Misc. Removal)
Worker
Central
Tendency
104
33
687
(PF 10)
218
(PF 10)
High-
End
5.9
0.7
46
(PF 10)
(>
(IT 10)
ONU
Central
Tendency
-
566
N/A
N/A
High-
End
14
N/A
N/A
Section 2.4.1.2.6 -
Removal of Paints,
„ j , Central
Worker „ ,
1endency
27
5.0
270
(PF 10)
51
(PF 10)
Page 289 of 487
-------
PEER REVIEW DRAFT, DO NOT CITE OR QUOTE
Mil- ( } I'll' Sl;l«>i-/ (
Sul>c;ik-<>»rk
I.\|>omiiv Si'i-n:irio
Coatings, Adhesives,
and Sealants
(Graffiti Removal)
Poituhilion
r.\|)(isuri'
l.l'M'l
Risk r.slim;ll
.Willi-
(Iti-ni'h 111:1 rk
MOI. = 30)
is lor \o ITI.
(Iironk-
\oll-l'illH'lT
(Iti-ni'h 111:1 rk
MOI. = 30)
Risk Llsiini;
.Willi-
\on-i';mi'iT
(Iti-ni-h iii;i rk
MOI. = 30)
li-s uiih PIT.
Chronic
Noll-l'Wll'lT
(Iti-ni'h 111:1 rk
M()i: = 30)
I Iigli-
Knd
7.4
0.')
85
(PF 10)
10
(IT 10)
()NI J
Central
Tendency
920
N/A
N/A
High-
End
-
196
N/A
N/A
Lacquers, stains, varnishes, primers and floor
finishes
Section 2.4.1.2.7 -
Application of Paints.
Coatings, Adhesive^.
and Sealants
(Spray Application)
Winker
( entral
Tendency
690
130
5152
(PF 10)
976
(PF 10)
Powder coatings (surface preparation)
High-
End
8.7
1.0
97
(PF 10)
12
(IT 10)
ONI J
( entral
Tendency
-
3,525
N/A
N/A
ITigh-
1 ind
-
197
N/A
N/A
Industrial, commercial, and
consumer use/Paint
additives and coating
additives not described by
other codes
Use in Computer and Electronic Product
Manufacturing, Construction, Fabricated
Metal Product Manufacturing, Machinery
Manufacturing, Other Manufacturing, Paint
and Coating Manufacturing, Primary Metal
Manufacturing, Transportation Equipment
Manufacturing, Wholesale and Retail Trade
Section 2.4.1.2.7-
Application of Paint s.
Coatings, Adhesives.
and Sealants
(Roll/Curtain)
Worker
Central
Tendency
714
134
6880
(PF 10)
1294
(PF 10)
Higli-
End
S.S
1.0
103
(PF 10)
12
(IT" 10)
ONU
Central
Tendency
-
30,904
N/A
N/A
High-
End
-
3,522
N/A
N/A
Industrial, commercial, and
consumer use/Adhesives
and sealants
Adhesives and sealant chemicals including
binding agents
Section 2.4.1.2.7 -
Application of Paints,
Coatings. Adhesives,
and Sealants
(Dip)
Worker
Central
Tendency
623
118
2,092
(PF 10)
556
(PF10)
Single component glues and adhesives,
including lubricant adhesives
High-
End
S.S
1.0
99
(PF 10)
12
(IT" 10)
Two-component glues and adhesives.
including some resins
ONU
Central
Tendency
-
944
N/A
N/A
High-
End
-
321
N/A
N/A
Two-component glues and adhesives.
including some resins
Section 2.4.1.2.7 -
Application of Paints,
Coatings, Adhesives,
and Sealants
(Brush)
Worker
Central
Tendency
440
84
1003
(PF 10)
194
(PF 10)
High-
End
8.7
1.0
97
(PF 10)
12
(IT 10)
ONU
Central
Tendency
-
226
N/A
N/A
High-
End
-
215
N/A
N/A
Page 290 of 487
-------
PEER REVIEW DRAFT, DO NOT CITE OR QUOTE
Mil- ( } I'll' Sl;l«>i-/ ( ;lli-c;ik-<>»rk
I.\|>omiiv Si'i-n.irio
Poituhilion
r.\i>oMuv
l.l'M'l
Risk r.slim;ll
.Willi-
(l>i-ni'hm;irk
MOI. = 30)
is lor \o ITI.
(Iironii-
Ndii-i'iiiii'i'r
(Itiiii-hniiirk
MOI. = 30)
Risk Llsiini;
.Willi-
\on-i';mi'iT
(l)iiii-hin;irk
MOI. = 30)
li-s \>iih PIT.
Chronic
Non-i'imi'iT
(Iti-ni'h iii;i rk
M()i: = 30)
Industrial, commercial, and
consumer use/Solvents (for
cleaning or degreasing)
Use in Electrical Equipment, Appliance and
Component Manufacturing
Section 2.4.1.2.8 -
Electronic Parts
Manufacturing:
Electronics
(Container Handling,
Small Containers)
Worker
Central
Tendency
I'J
2.7
204 (PF 10)
29 (PF 10)
I Iigli-
I ind
4.7
0.4
65 (PF 10)
6(l>l 10)
ONU
Central
Tendency
1,225
N/A
N/A
High-
End
859
N/A
N/A
Industrial, commercial, and
consumer use/Ink, toner,
and colorant products
Printer Ink
Section 2.4.1.2.9 -
Printing and Writing:
Printing
Worker
( entral
Tendency
286
54
1,433
(PF 5)
269
(PF 5)
High-
End
78
<>.4
395
(PF 5)
48
(PF 5)
ONU
Central
Tendency
-
108,142
N/A
N/A
I Iigli-
End
-
5,001
N/A
N/A
Inks in writing
Section 2.4.1.2.9 -
Printing and Writing:
Writing
Worker
( entral
Tendency
232,401
115,998
1,165,010
(PF 5)
578,327
(PF 5)
High-
End
116,201
57,998
582,823
(PF 5)
289,149
(PF 5)
(>NU
Central
Tendency
-
5,784,391
N/A
N/A
High-
End
-
580,007
N/A
N/A
Industrial, commercial, and
consumer use/Processing
aids, specific to petroleum
production
Petrochemical Manufacturing
Section 2.4.1.2.3 -
Chemical Processing,
I Acluding Formulation
Worker
Central
Tendency
62
2<)
612 (PF 10)
291(PF 10)
High-
End
31
14
301 (PF 10)
143
(PF 10)
ONU
Central
Tendency
-
11,255
N/A
N/A
High-
End
-
3,343
N/A
N/A
Industrial, commercial, and
consumer use/Other uses
Other uses in ()il and Gas Drilling.
Extraction and Support Activities
Section 2.4.1.2.3 -
Chemical Processing,
Excluding Formulation
Worker
Central
Tendency
62
2")
612 (PF 10)
291
(PF 10)
Pharmaceutical and Medicine Manufacturing
- functional fluids (closed systems)
High-
End
31
14
301 (PF 10)
143(PF 10)
™,-n-T Central
ONU „ ,
1endency
-
11,255
N/A
N/A
Page 291 of 487
-------
PEER REVIEW DRAFT, DO NOT CITE OR QUOTE
Risk r.siiimiii's lor No 1*1*1-"
Risk r.siini;ik-s \>ilh 1*1*1".
Mil- ( } I'll' Sl;l«>i-/ ( ';lli-<>on
Sultcailc^on
I.\|>omiii- Si'i-iiiirio
l*o|>ul;ilion
r.\|)(isuri'
l.l'M'l
.Willi-
(hi-ni-hm;irk
MOI. = 30)
Chronic
Non-i'iiiH'iT
(hi-ni-hm.irk
MOI. = 30)
Ai-uli-
Noll-l'lUll'lT
(hi-ni-hm;irk
MOI. = 30)
Chronic
Non-i'imi'i-r
(hi-ni'h iii;i rk
MOI! = 30)
I Iigh-
I ind
-
3.343
N/A
N/A
Lithium ion batteries
Section 2.4.1.2.8 -
Central
24
3.3
251 (PF 10)
36
Electronic Parts
Worker
Tendency
(PF 10)
Manufacturing:
Electronics
High-
End
4.7
0.4
64(PF 10)
6
(1*1 10)
(Container Handling.
Drums)
()Nl J
Central
T endency
-
42.649
N/A
N/A
High-
End
-
368
N/A
N/A
Section 2.4.1.2.8 -
Central
82
820
117
Electronic Parts
Winker
Tendency
(PF10)
(PF 10)
Manufacturing:
Electronics
I Iigh-
I ind
3.2
0.3
48
(PF 10)
4
(1*1 10)
(Fab Worker)
ONI J
Central
Tendency
-
4,502
N/A
N/A
High-
End
-
1,137
N/A
N/A
Section 2.4.1.2.8 -
Electronic Parts
Worker
Central
Tendency
21
3.0
228 (PF 10)
32
(PF 10)
Manufacturing:
Electronics
High-
End
3.2
0.3
48
(PF 10)
4
(1*1 10)
(Maintenance)
ONU
Central
Tendency
-
28,624
N/A
N/A
High-
End
-
739
N/A
N/A
Section 2.4.1.2.8 -
Electronic Parts
Worker
Central
Tendency
13
2.3
125 (PF 10)
2T.
(PF 10)
Manufacturing:
Electronics
High-
End
4.1
0.5
52
(PF 10)
6
(1*1 10)
(Virgin NMP Truck
Unloading)
ONU
Central
Tendency
-
195
N/A
N/A
High-
End
-
184
N/A
N/A
Section 2.4.1.2.8 -
Electronic Parts
Worker
Central
Tendency
14
2.6
151 (PF 10)
28
(PF 10)
Manufacturing:
Electronics
High-
End
4.6
0.5
59
(PF 10)
7
(1*1 10)
Page 292 of 487
-------
PEER REVIEW DRAFT, DO NOT CITE OR QUOTE
Mil- ( } I'll' Sl;l«>i-/ ( ;lli-»n
I.\|>omiiv Si'i-iiiirio
(Waste Truck
Unloading)
Po|>ul;ilion
r.\i>oMiiv
l.l'M'l
Risk r.slim;ll
.Willi-
(l>i-ni'hm;irk
MOI. = 30)
is lor \o PPI.
(Iironii-
Ndll-l'illH'l'l'
(Itiiii-hniiirk
MOI. = 30)
Risk Llsiini;
.Willi-
\on-i';mi'i'r
(l>iiii-hm;irk
MOI. = 30)
li-s \>iih PPI".
(lironii-
\on-i';mi'i'r
(l)i'iii-hni;irk
MOI! = 30)
ONU
Central
Tendency
-
1,313
N/A
N/A
High-
End
1,097
N/A
N/A
Soldering materials
Section 2.4.1.2.10 -
Soldering
Worker
Central
Tendency
1.436
270
14376(PF
10)
2701
(PF 10)
High-
End
111
27
2242(PF 10)
270
(PF 10)
ONI J
( entral
Tendency
-
7,224,526
N/A
N/A
High-
End
-
289,802
N/A
N/A
Anti-freeze and de-icing products
Automotive care products
Section 2.4.1.2.1 1 -
Commercial
Automotive Servicing
Winker
Central
Tendency
624
199
1,090
(PF 10)
344
(PF 10)
Lubricants and greases
I Iigli-
End
14
1.6
84
(PF10)
10
(PI 10)
ONI J
( entral
Tendency
-
374
N/A
N/A
High-
End
21
N/A
N/A
Metal products not covered elsewhere
Section 2.4.1.2.5 -
Metal Finishing
(Spray Application)
Worker
Central
Tendency
23
4.2
235
(PF 10)
44
(PF 10)
High-
End
4.7
0.5
58
(PF 10)
7
(PI 10)
ONU
Central
Tendency
-
3,428
N/A
N/A
High-
End
-
195
N/A
N/A
Section 2.4.1.2.5 -
Metal Finishing
Pip)
Worker
Central
Tendency
23
4.2
227
(PF 10)
43
(PF 10)
High-
End
4.7
0.5
59
(PF 10)
7
(PI 10)
ONU
Central
Tendency
-
937
N/A
N/A
High-
End
-
316
N/A
N/A
„ T , Central
Worker _ ,
1endency
22
4.1
198
(PF 10)
37
(PF 10)
Page 293 of 487
-------
PEER REVIEW DRAFT, DO NOT CITE OR QUOTE
Mil- ( } I'll' Sl;l«>i-/ ( ;lli-»n
l.\|)«)suiv Si-i-ii.irio
Section 2.4.1.2.5 -
Metal Finishing
(Brush)
Poituhilion
r.\|)(isuri'
l.l'M'l
Risk r.slim;ll
.Willi-
(l>i-ni'hm;irk
MOI. = 30)
is lor \o PIT.
(Iironii-
Ndii-i'iiiii'i'r
(Itiiii-hniiirk
MOI. = 30)
Risk Llsiini;
.Willi-
\on-i';mi'iT
(l)iiii-hin;irk
MOI. = 30)
li-s \>iih PIT.
(Iironii-
\on-i';mi'iT
(l>i-ni-h iii;i rk
M()i: = 30)
High-
I ind
4.7
0.5
58
(PF 10)
7
(PI 10)
(>NU
Central
Tendency
22b
N/A
N/A
High-
End
213
N/A
N/A
Lubricant and lubricant additives, including
hydrophilic coatings
Section 2.4.1.2.5 -
Metal Finishing
(Spray Application)
Worker
Central
Tendency
23
4.2
235
(PF 10)
44
(PF 10)
I ligh-
End
4.7
0.5
58
(PF 10)
7
(IT 10)
ONI J
( entral
Tendency
-
3,428
N/A
N/A
I Iigh-
I ind
-
195
N/A
N/A
Section 2.4.1.2.5 -
Metal Finishing
(Dip)
Worker
Central
Tendency
23
4.2
227
(PF 10)
43
(PF 10)
I ligh-
End
4.7
0.5
59
(PF 10)
7
(IT 10)
ONU
Central
Tendency
-
937
N/A
N/A
High-
End
-
316
N/A
N/A
Section 2.4.1.2.5 -
Metal Finishing
(Brush)
Worker
Central
Tendency
22
4.1
198
(PF 10)
37
(PF 10)
High-
End
4.7
0.5
58
(PF 10)
7
(IT 10)
ONU
Central
Tendency
-
226
N/A
N/A
High-
End
-
213
N/A
N/A
Laboratory chemicals
Section 2.4.1.2.12 -
Laboratory Use
Worker
Central
Tendency
21
5.0
214
(PF 10)
53
(PF 10)
High-
End
4.1
0.5
52
(PF 10)
6
(IT 10)
ONU
Central
Tendency
-
17,565
N/A
N/A
High-
End
-
225
N/A
N/A
Page 294 of 487
-------
PEER REVIEW DRAFT, DO NOT CITE OR QUOTE
l.ili- ( } I'll' ( ;ili-»n
I.\|>omiiv Si'i-n.irio
Po|>ul;ilion
r.\|)(isuri'
l.l'M'l
Risk Lislilllill
.Willi-
(l>i-ni'hm;irk
MOI. = 30)
is lor \o PPI.
(Iironk-
Ndii-i'iini'i'r
(Itiiii-hniiirk
MOI. = 30)
Risk Lisiini;
.Willi-
\on-i';mi'iT
(l)iiii-hin;irk
MOI. = 30)
li-s \>iih PIT.
Chronic
Non-i'imi'iT
(Iti-ni'h iii;i rk
MC)i: = 30)
Cleaning and furniture cure products,
including wood cleaners, gasket removers
Section 2.4.1.2.13 -
Cleaning
(Dip Cleaning)
Worker
Central
Tendency
l()
2.')
163
(PF 10)
31
(PF 10)
I Iigli-
I ind
4.1
0.5
53
(PF 10)
(>
(PI 10)
ONU
Central
Tendency
934
N/A
N/A
High-
End
314
N/A
N/A
Section 2.4.1.2.13 -
Cleaning
(Spray/Wipe Cleaning)
Worker
Central
Tendency
44
S.2
418
(PF 10)
79
(PF 10)
High-
I ind
4.2
0.5
53
(PF 10)
6
(PI 10)
ONU
Central
Tendency
-
922
N/A
N/A
I Iigli-
End
-
258
N/A
N/A
Fertilizer and other agricultural chemical
manufacturing-processing aids and solvents
Section 2.4.1.2.14 -
Fertilizer Application
Worker
( entral
Tendency
1,430
279
1,587
(PF 5)
307
(PF5)
High-
End
74
S.<)
310
(PF 5)
38
(PF 5)
(>NU
Central
Tendency
-
315
N/A
N/A
High-
End
-
171
N/A
N/A
Wood preservatives
Section 2.4.1.2.15 -
Wood Preservatives
Worker
Central
Tendency
635
122
1,003
(PF5)
194
(PF5)
High-
End
426
52
1,099
(PF5)
135
(PF 5)
ONU
Central
Tendency
-
226
N/A
N/A
High-
End
-
219
N/A
N/A
6683
6684 N/A = not assessed because ONUs are 1101 assumed lo be wearing PPE; - = exposure data for ONUs were not available
6685
6686
6687
6688
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6689 Table 4-51. Summary of Risk Estimates from Acute Exposures to Consumers by Conditions of Use
Life Cycle Slji»e/
C:ilcj>ory
Suhcsile«»ory
Consumer Condition of
I se/K\posure Scenario
Population
Lxposure Ley el
Risk Lsliniiile
Acute Non-csincer
(hencliinnrk MOL = 30)
Industrial,
commercial, and
consumer use/
Paints and
coatings
Paint and coating removers
Section 2.4.2.5,
Paint Removers
Consumer
Medium-Intensity User
107
1 hull-Intensity User
22
By slander
Medium-Intensity User
N/A
High-Intensity I scr
N/A
Adhesive removers
Section 2.4.2.5,
Adhesive Removers
( onsumer
Medium-Intensity User
167
High-Intensity User
36
Bystander
Medium-Intensity User
N/A
High-Intensity User
N/A
Lacquer, stains, varnishes,
primers and floor finishes
Section 2.4 2 5.
Stains, Varnishes
( onsumer
Medium-Intensity User
633
High-Intensity User
111
Bystander
Medium-Intensity User
N/A
High-Intensity User
N/A
Industrial,
commercial, and
consumer use/
Paint additives and
coatings additives
not described by
other codes
Use in Computer and
Electronic Product
Manufacturing, Construction.
Fabricated Metal Product
Manufacturing. Machine^
Manufacturing. Other
Manufacturing, Paint and
Coating Manufacturing,
Primary Metal Manufacturing,
Transportation Equipment
Manufacturing. Wholesale and
Retail Trade
Section 2 4 2 5.
Paint
(onsumer
Medium-Intensity User
578
High-Intensity User
152
Bystander
Medium-Intensity User
N/A
High-Intensity User
N/A
Section 2 4.2.5.
Arts and Crafts
Consumer
Medium-Intensity User
3,034
High-Intensity User
974
Bystander
Medium-Intensity User
N/A
High-Intensity User
N/A
Industrial,
commercial, and
Section 2.4.2.5,
Adhesives
Consumer
Medium-Intensity User
174
High-Intensity User
38
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Life C ycle Slji»c/
("silcsory
consumer use
adhesives and
sealants
Suhcsilc«»ory
Single component glues and
adhesives, including lubricant
adhesives
Consumer Condition of
I sc/K\posurc SiTiiiirio
Population
KxpOMIIT I.CM'I
Risk Ksliniiilc
Acute Noii-c:iiicer
(benchin;irk MOK = 30)
1 bystander
Medium-Intensity User
N/A
1 ligh-Intensity User
N/A
Two-component glues and
adhesives, including some
resins
Section 2.4.2.5,
Sealants
Consumer
Med in ni-Intensity User
19,115
High-lnlensily User
3,086
IJ\ slander
Medium-lnlensih User
N/A
High-Intensily User
N/A
Industrial,
commercial, and
consumer use/
Other uses
Automotive care products
Section 2.4.2.5,
Auto Interior ( leaner
Consumer
Medium-Intensity User
844
High-Intensity User
50
|}\ slander
Medium-Intensity User
N/A
High-Intensity User
N/A
Seclion 2 4.2.5.
Aulo Interior Spray
(leaner
( onsumer
Medium-Intensity User
2,323
High-Intensity User
1,180
Bystander
Medium-Intensity User
N/A
High-Intensity User
N/A
Cleaning and furniture care
products, including wood
cleaners, gasket removers
Seclion 2 4 2 5.
Cleaners l)eg leaser
Consumer
Medium-Intensity User
209
High-Intensity User
k>
Bystander
Medium-Intensity User
N/A
High-Intensity User
53
Seclion 2.4.2.5,
1 Engine Cleaner/
Degreaser
Consumer
Medium-Intensity User
128
High-Intensity User
13
Bystander
Medium-Intensity User
N/A
High-Intensity User
39
Section 2.4.2.5,
Consumer
Medium-Intensity User
651
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Life C ycle Slji»e/
Csilesorv
Industrial,
commercial, and
consumer use/
Other uses
Suhcsilc«»orv
Lubricant and lubricant
additives, including
hydrophilic coatings
Consumer C Oil (lit ion of
I se/Kxposure Scen:irio
Spra\ Lubricant
Population
KxpOSIII'C I.C\cl
Risk Kslim;ilc
Acute Noii-c:iiicer
(hen chili;) rk MOK = 30)
1 liijli-lntensity User
76
Bystander
Medium-Intensity User
N/A
1 liijh-lnleiisity User
N/A
N/A = not assessec
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5 Risk Determination
5.1 Unreasonable Risk
5.1.1 Overview
In each risk evaluation under TSCA section 6(b), EPA determines whether a chemical substance
presents an unreasonable risk of injury to health or the environment, under the conditions of use. These
determinations do not consider costs or other non-risk factors. In making these determinations, EPA
considers relevant risk-related factors, including, but not limited to: the effects of the chemical substance
on health and human exposure to such substance under the conditions of use (including cancer and non-
cancer risks); the effects of the chemical substance on the en\ ironment and environmental exposure
under the conditions of use; the population exposed (including any potentially exposed or susceptible
subpopulations (PESS)); the severity of hazard (including the nature of the hazard, the irreversibility of
the hazard); and uncertainties. EPA also takes into consideration the Agency's confidence in the data
used in the risk estimate. This includes an evaluation of the strengths, limitations and uncertainties
associated with the information used to inform the risk estimate and the risk characterization. This
approach is in keeping with the Agency's final rule, Procedures for ('hemical Risk Evaluation Under the
Amended Toxic Substances Control. let (82 FR 33726)/'
Under TSCA, conditions of use are defined as the circumstances, as determined by the Administrator,
under which the substance is intended, known, or reasonably foreseen to be manufactured, processed,
distributed in commerce, used, or disposed of TSCA §3(4).
An unreasonable risk may he indicated u hen health risks under the conditions of use are identified by
comparing the estimated risks with the risk benchmarks and where the risks affect the general
population or PESS identified as rele\ ant I or workers (which are one example of PESS), an
unreasonable risk may be indicated when risks are not adequately addressed through expected use of
workplace practices and exposure controls, including engineering controls or use of personal protective
equipment (PPE) An unreasonable risk may also be indicated when environmental risks under the
conditions of use are greater than environmental risk benchmarks. The risk estimates contribute to the
evidence EPA uses to determine unreasonable risk.
EPA uses the term "indicates unreasonable risk" to indicate EPA concern for potential unreasonable
risk. For non-cancer endpoints, "less than MOE benchmark" is used to indicate potential unreasonable
risk; this occurs if an MOE value is less than the benchmark MOE (e.g., MOE 0.3 < benchmark MOE
30). For cancer endpoints, EPA uses the term "greater than risk benchmark" to indicate potential
unreasonable risk; this occurs, for example, if the lifetime cancer risk value is greater than 1 in 10,000
(e.g., cancer risk value is 5xl0"2 which is greater than the standard range of acceptable cancer risk
6 This risk determination is being issued under TSCA section 6(b) and the terms used, such as unreasonable risk, and the
considerations discussed are specific to TSCA. Other statutes have different authorities and mandates and may involve risk
considerations other than those discussed here.
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benchmarks of lxlO"4 to lxlO"6). For environmental endpoints, to indicate potential unreasonable risk
EPA uses a risk quotient (RQ) value "greater than 1" (i.e., RQ >1). Conversely, EPA uses the term
"does not indicate unreasonable risk" to indicate that it is unlikely that EPA has a concern for potential
unreasonable risk. More details are described below.
The degree of uncertainty surrounding the MOEs, cancer risk or RQs is a factor in determining whether
or not unreasonable risk is present. Where uncertainty is low, and EPA has high confidence in the
hazard and exposure characterizations (for example, the basis for the characterizations is measured or
monitoring data or a robust model and the hazards identified for risk estimation are relevant for
conditions of use), the Agency has a higher degree of confidence in its risk determination.
EPA may also consider other risk factors, such as severity of endpoint, reversibility of effect, or
exposure-related considerations, such as magnitude or number of exposures, in determining that the
risks are unreasonable under the conditions of use. Where EPA has made assumptions in the scientific
evaluation, whether or not those assumptions are protecli\ e will also be a consideration Additionally,
EPA considers the central tendency and high-end scenarios when determining the unreasonable risk.
High-end risk estimates (i.e., 95th percentile) are generally intended to cover individuals or sub-
populations with greater exposure (PESS) and central tendency risk estimates are generally estimates of
average or typical exposure.
EPA may make a no unreasonable risk determination lor conditions of use where the substance's hazard
and exposure potential, or where the risk-related factors described pie\ iously, lead EPA to determine
that the risks are not unreasonable.
5.1.2 Risks lo 1111111:111 llcsillh
5.1.2.1 DcU'niiining Non-Csinccr Risks
Margins of exposure fUOEs) are used in I .IWs risk evaluations as a starting point to estimate non-
cancer risks for acute and chronic exposures. The non-cancer evaluation refers to potential adverse
health effects associated with health endpoints other than cancer, including to the body's organ systems,
such as reproductive/developmental effects, cardiac and lung effects, and kidney and liver effects. The
MOE is the point of departure (POD) (an approximation of the no-observed adverse effect level
(NOAEI.) or benchmark dose level (BMDL)) for a specific health endpoint divided by the exposure
concentration for the specific scenario of concern. The benchmark for the MOE that is used accounts for
the total uncertainly in a POD, including, as appropriate: (1) the variation in sensitivity among the
members of the human population (i.e., intrahuman/intraspecies variability); (2) the uncertainty in
extrapolating animal data to humans (i.e., interspecies variability); (3) the uncertainty in extrapolating
from data obtained in a study with less-than-lifetime exposure to lifetime exposure (i.e., extrapolating
from sub-chronic to chronic exposure); and (4) the uncertainty in extrapolating from a lowest observed
adverse effect level (LOAEL) rather than from a NOAEL. MOEs can provide a non-cancer risk profile
by presenting a range of estimates for different non-cancer health effects for different exposure scenarios
and are a widely recognized point estimate method for evaluating a range of potential non-cancer health
risks from exposure to a chemical.
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6789
6790
6791
6792
6793
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6797
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6799
6800
6801
6802
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A calculated MOE that is less than the benchmark MOE indicates the possibility of risk to human health.
Whether those risks are unreasonable will depend upon other risk-related factors, such as severity of
endpoint, reversibility of effect, exposure-related considerations (e.g., duration, magnitude, frequency of
exposure, population exposed), and the confidence in the information used to inform the hazard and
exposure values. If the calculated MOE is greater than the benchmark MOE, generally it is less likely
that there is risk.
Uncertainty factors (UFs) also play an important role in the risk estimation approach and in determining
unreasonable risk. A lower benchmark MOE (e.g., 30) indicates greater certainty in the data (because
fewer of the default UFs relevant to a given POD as described above were applied). A higher benchmark
MOE (e.g., 1000) would indicate more uncertainty in risk estimation and extrapolation for the MOE for
specific endpoints and scenarios. However, these are often not the only uncertainties in a risk evaluation.
5,1.3 Determining Environmental Risk
To assess environmental risk, EPA identifies and evaluates en\ ironmental hazard data for aquatic,
sediment-dwelling, and terrestrial organisms exposed under acute and chronic exposure conditions. The
environmental risk includes any risks that exceed benchmarks to the aquatic environment from levels of
the evaluated chemical released to the en\ ironnient (e.g., surface water, sediment, soil, biota) under the
conditions of use, based on the fate properties, release potential, and reasonably available environmental
monitoring and hazard data.
Environmental risks are estimated by calculating a RQ The RQ is defined as:
RQ = I-n\ ironmental Concentration / Effect Level
An RQ equal to 1 indicates that the exposures are the same as the concentration that causes effects. If the
RQ is greater than 1, the exposure is greater than the effect concentration and there is potential for risk
presumed. If the RQ is less than 1, the exposure is less than the effect concentration and unreasonable
risk is not likely. The Concentrations of Concern or hazard value for certain aquatic organisms are used
to calculate RQs for acute and chronic exposures. For environmental risk, EPA is more likely to
determine that there is unreasonable risk if the RQ exceeds 1 for the conditions of use being evaluated.
Consistent with I'.PA's human health e\ aluations, the RQ is not treated as a bright line and other risk-
based factors may be considered (e.g., exposure scenario, uncertainty, severity of effect) for purposes of
making a risk determination
5.2 Risk Determination for NMP
EPA's determinations of unreasonable risk for specific conditions of use of NMP listed below are based
on health risks to workers during occupational exposures, including occupational non-users in certain
exposure scenarios; and health risks to consumers. With respect to cancer risks, as discussed in section
2.4.2.2 of the Problem Formulation of the Risk Evaluation for NMP, NMP is not mutagenic and is not
considered carcinogenic so EPA did not conduct analysis of genotoxicity and cancer hazards during risk
evaluation. For the conditions of use where EPA found no unreasonable risk, EPA describes the
estimated risks in Section 4 (Table 4-49 and Table 4-50).
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As described in section 3, significant risks associated with more than one adverse effect were identified
for particular conditions of use. In the table below, EPA identifies either reproductive effects or adverse
developmental effects as the unreasonable risk driver for the conditions of use, depending on whether
acute or chronic exposure was assessed. The effects identified as the unreasonable risk driver vary
because chronic exposures typically involve repeated doses, such as in an occupational setting, in
contrast to acute exposures in a consumer setting.
EPA selected reduced fertility as the basis for evaluating risks from chronic exposures. This is described
as reproductive toxicity in the risk determination and throughout the risk evaluation. EPA determined
that this is an appropriate endpoint for evaluating chronic risk because it is a sensitive effect observed in
a high-quality study and it is supported by robust evidence for a continuum of reproductive and
developmental effects across several studies. EPA has selected fetal resorptions (mortality), an adverse
developmental effect, as the basis for evaluating risks from acute exposures. I -P A determined that this
endpoint is the most applicable to assessing risks from acute exposures, where the risk ol'their
occurrence is assumed to depend on exceedance of a threshold value for even a single day (i e., peak
concentration) rather than a time weighted average value and the magnitude of the exposure is
considered more important for these effects under these study conditions.
The previous EPA assessment did not characterize dose-response lor these fertility endpoints because
the effect observed in one study was not replicated in more recent studies. However, together, the acute
and chronic effects indicate a continuum of reproductive and developmental effects associated with
NMP exposure. The complete basis for selection of endpoints is described in detail in section 3.2.5.1
(Selection of Endpoints for Dose-Response Assessment) and section 3.2.5.6 (Points of Departure for
Human Health Hazard Endpoints).
As described below, risks to the en\ ironment, general population, occupational non-users (ONUs) and
bystanders from consumer use either were not relevant for these conditions of use or were evaluated and
found not to be unreasonable
• Environmental risks: I or all conditions of use, EPA did not identify any scenarios indicating
unreasonable risk for aquatic, sediment-dwelling, or terrestrial organisms from exposures to
\ VIP NMP readily degrades under aerobic conditions and is not expected to persist in the
en\ ironment. A screening level risk analysis for NMP in surface water and aquatic receptors
resulted in RQs for the acute and chronic risk of 0.0022 and 0.85, respectively (Table 4-2). An
RQ that does not exceed 1 indicates that the exposure concentrations of NMP are less than the
concentrations that would cause an effect to organisms in the aquatic pathways. Because the RQ
values do not exceed 1, and because EPA used a conservative screening level approach, these
values indicate that the risks of NMP to the aquatic organisms are unlikely. In addition, NMP is
unlikely to accumulate in sediment based on NMP's physical chemical properties. NMP is not
expected to adsorb to sediment due to its water solubility and low partitioning to organic matter.
Because NMP toxicity to sediment-dwelling organisms is expected to be comparable to that of
aquatic organisms, minimal risks are anticipated for sediment-dwelling organisms. NMP exhibits
low volatility and readily biodegrades under aerobic conditions; therefore, the concentrations in
ambient air are unlikely to reach levels that would present risks for terrestrial organisms. As a
result, EPA does not find unreasonable risks to the environment for the conditions of use for
NMP.
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• General Population: EPA is not including general population exposures in the risk evaluation
for NMP. As explained in the Problem Formulation for the Risk Evaluation for NMP, general
population exposures were determined to be outside the scope of the risk evaluation. EPA has
determined that the existing regulatory programs and associated analytical processes adequately
assess and effectively manage the risks of NMP that may be present in various media pathways
(e.g. air, water, land) for the general population. For these cases, EPA believes that the TSCA
risk evaluation should not focus on those exposure pathways, but rather on exposure pathways
associated with TSCA conditions of use that are not subject to those regulatory processes,
because the latter pathways are likely to represent the greatest areas of concern to EPA.
• Occupational Non-Users: EPA's exposure assessment includes estimates of NMP exposures to
occupational non-users (ONUs). ONUs are located in the general vicinity near workers but are
further from emissions sources. Unlike workers, ONUs do not have direct dermal contact with
liquids. The estimates assume ONUs are not wearing respirators. While the difference between
ONU exposures and workers directly handling the chemical generally cannot be quantified, EPA
assumes that, in most cases, ONU inhalation exposures are expected to be lower than inhalation
exposures for workers directly handling the chemical substance. To account for those instances
where monitoring data or modeling did not distinguish between worker and ONU inhalation
exposure estimates, EPA considered the central tendency risk estimate when determining ONU
risk. As a result, while high-end chronic exposures indicate risks for ONUs, risk estimates for
ONUs for the central tendency scenarios did not indicate risk. EPA determined that the
conditions of use assessed did not present an unreasonable risk for ONUs.
• Bystanders (to uses bv consumers): EPA's exposure assessment includes estimates of NMP
exposures to bystanders (i e those located in the house during consumer product use) who do not
have direct contact with WIP-containing consumer products. EPA did not identify risks to
bystanders to consumer uses and has determined that the conditions of use assessed do not
present an unreasonable risk to In slanders
Table 5-1. NMP Kisk Determinations by Conditions of Use
Life Cycle
Stage
C Oil (lit i
Category
til of I se
Sub-Category
I nreasonahle kisk Determination1
\ lanufacture
Domestic
Manufacture
Domestic Manufacture
Section 6(b)(4)(A) unreasonable risk determination
for domestic manufacture of NMP:
- Does not present an unreasonable risk of injury to
health (workers, occupational non-users).
Exposure scenario with highest risk estimates:
Reproductive effects from chronic inhalation and
dermal exposure.
Benchmark: MOE = 30 for reproductive effects.
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Life Cycle
Slsi«e
( Oil (lit i
CsiU'Sorv
>11 of I so
Suh-CsiU'Korv
I nroiisoiiiihle Risk Dclcrminjilion1
Risk Estimate. MOL 48 with workers using glo\ es
(PF = 20) (high-end scenario) (Table 4-6).
Systematic Review confidence rating (hazard): Hiah.
Systematic Re\ lew confidence ratine (exposure):
Medium.
Risk Considerations While I he chronic risk
estimates for both central tendency and high-end
exposure in the absence of PPL indicate risk, risk
estimates for central tendency and high-end exposure
do not indicate risk, when expected use of PPE was
considered (gloves PF = 20) (Table 4-6).
LP A relied on data, models, or a combination to
estimate exposure and then estimate risk from NMP
for this condition of use. Relevant factors that may
generate uncertainties and affect the risk calculations
include representativeness and age of the data for the
condition of use. as well as assumptions about glove
use. glo\ e eflcctivencss, duration of contact with
WIP. concentration of NMP, and amount of skin
surface contact with NMP. The primary limitations
of the exposure scenario inputs and models for this
condition of use are in Section 2.4.1.2.1.
Estimated exposed population: 2.800 workers.
Manufacture
1 ill porl
1 ill pol l
Section 6(b)(4)(A) unreasonable risk determination
for manufacture - import of NMP:
- Does not present an unreasonable risk of injury to
health (workers, occupational non-users).
Exposure scenario with highest risk estimate:
Reproductive effects from chronic inhalation and
dermal exposure.
Benchmark: MOE = 30 for reproductive effects.
Risk Estimate: MOE = 25 with workers using gloves
(PF = 10) (high-end scenario) (Table 4-8).
Systematic Review confidence ratine (hazard): Hiah.
Systematic Review confidence rating (exposure):
Medium.
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Life Cycle
Slsi«e
Coiulili
CsiU'Sorv
>11 of I so
Suh-CsiU'Korv
I nroiisoiiiihle Risk l)clcrniin;ili<)iii : i
Risk Considerations. While llie hmh-end scenario
risk estimates indicate risk in the absence of PPE and
when expected use of PPE was considered (gloves
PF = 10), given the uncertainties in the model, these
were not considered unreasonable risks (Table 4-8).
While the chronic central tendency scenario risk
estimate indicates risk in the absence of PPE, risk
estimates for the central lendency scenarios do not
indicate risk (MOE 213) w hen expected use of
PPE was considered (glows PF = 10) (Table 4-8).
LPA relied on data, models, or a combination to
estimate exposure and then eslimale risk fromNMP
lor lliis condition of use. Relevant factors that may
generate uncertainties and affect the risk calculations
include representativeness and age of the data for the
condition of use. as well as assumptions about glove
use. glo\ e el'lecli veness. duration of contact with
NMP. concentration of NMP, and amount of skin
sui lace contact with NMP. The primary limitations
ol'lhe exposure scenario inputs and models for this
condition of use arc in Section 2.4.1.2.2.
Estimated exposed population: 1.100 workers.
Processing
Processing as
a ivaclanI or
intermediate
1 iiLcnnodialc in Plastic
Material and Resin
Manufacturing and in
Pharmaceutical and
Medicine Manufacturing
Section 6(b)(4)(A) unreasonable risk determination
for processing NMP as a reactant or intermediate in
several manufacturing processes:
- Does not present an unreasonable risk of injury to
health (workers, occupational non-users).
Exposure scenario with highest risk estimate:
Reproductive effects from chronic inhalation and
dermal exposure.
Benchmark: MOE = 30 for reproductive effects.
Risk Estimate: MOE =143 with workers using
gloves (PF =10) (high-end scenario) (Table 4-10).
Systematic Review confidence rating (hazard): Hieh.
Systematic Review confidence ratine (exposure):
Medium.
Risk Considerations: While the risk estimates for the
chronic central tendency and high-end scenarios
indicate risk in the absence of PPE, risk estimates for
Other
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the central lendcncx and high-end scenarios do 110L
indicate risk when expected use of PPE was
considered (gloves PF = 10) (Table 4-10). EPA
relied on data, models, or a combination to estimate
exposure and then estimate risk from NMP for this
condition of use. Relevant factors that may generate
uncertainties and affect the risk calculations include
representativeness and age of the data for the
condition of use. as well as assumptions about glove
use, glove effectiveness, duration of contact with
NMP. concentration of NMP. and amount of skin
surface contact with NMP. The primary limitations
of the exposure scenario inputs and models for this
condition of use arc in Section 2.4.1.2.3.
Estimated exposed population: 5,400 workers.
Processing
Incorporated
into
formulation,
mixture or
reaction
product
Adhesives and sealant
chemicals in Adhesi\ e
Manufacturing
Section 0(b)(4)(A) unreasonable risk determination
lor processing NMP for incorporation into a
Ioi inillation, mixture or reaction product, in several
industrial sectors:
Anti-adhesi\e agents in
Printing and Related Support
Activities
Paint additives and coating
additives noi described by
other codes in Paint and
Coating Manufacturing; and
Print Ink Manufacturing
Plating agents and surface
treating agents in Fabricated
Metal Product
Manufacturing
- Presents an unreasonable risk of injury to
health (workers).
- Docs not present an unreasonable risk of injury to
health (occupational non-users).
Unreasonable risk driver: Reproductive effects from
chronic inhalation and dermal exposure.
Driver Benchmark: MOE = 30 for reproductive
effects.
Risk Estimates: MOE = 6 with workers using gloves
(PF =10) (high-end scenario) (Table 4-12).
Systematic Review confidence rating (hazard): High.
Processing aids not otherwise
listed in Plastic Material and
Resin Manufacturing
Solvents (for cleaning or
degreasing) in Non-Metallic
Mineral Product
Manufacturing; Machinery
Manufacturing; Plastic
Material and Resin
Systematic Review confidence rating (exposure):
Medium to High.
Risk Considerations: Worker unreasonable risk
determination reflects the severity of the effects
associated with chronic exposures, even in the
presence of expected PPE. The high-end scenario
risk estimates indicate risk even when expected use
of PPE was considered (gloves PF = 10). While the
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chronic central tcndenc\ scenario risk estimate
indicates risk in the absence of PPE, risk estimates
for the central tendency scenarios do not indicate risk
(MOE = 291) when expected use of PPE was
considered (gloves PF = 10) (Table 4-12). EPA
relied on data, models, or a combination to estimate
exposure and then estimate risk from NMP for this
condition of use. Relevant factors that may generate
uncertainties and affect the risk calculations include
representativeness and age of the data for the
condition of use. as well as assumptions about glove
use. glove effectiveness, duration of contact with
NMP. concentration of NMP, and amount of skin
surface contact with NMP. The primary limitations
of the exposure scenario inputs and models for this
condition of use are in Section 2.4.1.2.4.
Estimated exposed population: 1.900 workers.
Man ui'ac L uring, Primal)
Metal Manufacturing; Soap,
Cleaning Compound and
Toilet Preparation
Manufacturing;
Transportation Equipment
Manufacturing; All Other
Chemical Product and
Preparation Manufacturing;
Printing and Related Support
Activities; Services;
Wholesale and Retail Trade
Solvents (which become pai l
of product formulation or
mixture) in Electrical
Equipment, Appliance and
Component Manufacturing.
Other Manufacturing. Paint
and Coating Manufacturing.
Print Ink Manufacturing.
Soap. Cleaning Compound
and Toilet Preparation
Manufacturing:
Transportation Equipment
Manufacturing: All Other
Chemical Product and
Preparation Manufacturing.
Printing and Related Support
Acti\ ilies. Wholesale and
Retail 1 lade
Sin lace actn e agents in
Soap, Cleaning Compound
and Toilet Preparation
Manufacturing
Other uses in Oil and Gas
Drilling, Extraction and
Support Activities; Plastic
Material and Resin
Manufacturing; Services
Processing
Incorporated
into articles
Lubricants and lubricant
additives in Machinery
Manufacturing
Section 6(b)(4)(A) unreasonable risk determination
for processing NMP for incorooration into articles as
lubricants and lubricant additives in machinery
manufacturing:
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-Presents an unreasonable risk of injury to health
(workers).
- Does not present an unreasonable risk of injury to
health (occupational n on -users).
Unreasonable risk driver: Reproductive effects from
chronic inhalation and dermal exposure.
Driver Benchmark: MOE = 30 for reproductive
effects.
Risk Estimate: MOE = 7 Willi workers usinu: eloves
(I'l1' = 10) (high-end scenarios for spia\. dip, or brush
applications) (Table 4-18).
Svstemalic Review confidence ratine (hazard): High.
S\ stematic Re\ lew confidence ratine (exposure):
Medium
Risk Considerations: Worker unreasonable risk
deleiniiiKilion reflects the severity of the effects
associaled w ith chronic exposures, even in the
presence of expected PPE. The high-end scenario
risk estimates indicate risk even when expected use
of PPE was considered (gloves PF = 10). While the
chronic central tendency scenario risk estimate
indicates risk in the absence of PPE, risk estimates
for die central tendency scenarios do not indicate risk
(MOE = 44) when expected use of PPE was
considered (gloves PF = 10) (Table 4-18). EPA
relied on data, models, or a combination to estimate
exposure and then estimate risk from NMP for this
condition of use. Relevant factors that may generate
uncertainties and affect the risk calculations include
representativeness and age of the data for the
condition of use, as well as assumptions about glove
use, glove effectiveness, duration of contact with
NMP, concentration of NMP, and amount of skin
surface contact with NMP. The primary limitations
of the exposure scenario inputs and models for this
condition of use are in Section 2.4.1.2.5.
Estimated exposed population: 530.000 workers.
Processing
Incorporated
into articles
Paint additives and coating
additives not described by
Section 6(b)(4)(A) unreasonable risk determination
for processing NMP for incorporation into articles as
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other codes 111 Transportation
Equipment Manufacturing
Dai 11L addiln es and coaliim addiln es no I described
bv other codes in Transportation Ecimoment
Manufacturing:
- Presents an unreasonable risk of injury to
health (workers).
- Does not present an unreasonable risk of injury to
health (occupational non-users).
Unreasonable risk driver: Reproductive effects from
chronic inhalation and dermal exposure.
I)n\er Benchmark: MOE = 3d and fur reproductive
ellecls
Risk Lslimales. MOE = 12 with workers usine
glo\ es (IT 10) for spray, dip, roll curtain or brush
applications (high-end scenarios) (Table 4-14).
S\ slemalic Rev lew confidence ratine (hazard): High.
S\ slemalic Review confidence rating (exposure):
Medium
Risk Considerations: Worker unreasonable risk
determination reflects the severity of the effects
associated with chronic exposures, even in the
presence of expected PPE. For chronic exposures,
the high-end scenario risk estimates indicate risk in
the absence of PPE and even when expected use of
PPE was considered (gloves PF = 10). Risk estimates
for the central tendency scenarios did not indicate
risk (MOEs = 1294 to 194) in the absence of PPE
(Table 4-14). EPA relied on data, models, or a
combination to estimate exposure and then estimate
risk from NMP for this condition of use. Relevant
factors that may generate uncertainties and affect the
risk calculations include representativeness and age
of the data for the condition of assumptions about
glove use, glove effectiveness, duration of contact
with NMP, concentration of NMP, and amount of
skin surface contact with NMP. The primary
limitations of the use, as well as exposure scenario
inputs and models for this condition of use are in
Section 2.4.1.2.7.
Estimated exposed population: 2.000.000 workers.
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Processing
Incorporated
into articles
Solvents (which become part
of product formulation or
mixture), including in
Textiles, Apparel and
Leather Manufacturing
Section 6(b)(4)(A) unreasonable risk determination
for processing NMP for incorporation into articles as
a solvent (which becomes part of product
formulation or mixture), including in textiles, apparel
and leather manufacturing:
- Presents an unreasonable risk of injury to
health (workers).
- Does not present an unreasonable risk of injury to
health (occupational non-users).
1 nreasonable risk driver: Repmduclive effects from
chronic inhalation and dermal exposure
l)n\cr IJcnchnniik: MOE = 30 for reproductive
ellecls
Risk Eslimale \IOF = 6 with workers using gloves
(Pl; = lU) (hiijh-end scenario) (Table 4-12).
S\ slemalic Re\ lew confidence rating (hazard): Hieh.
S\ slemalic Review confidence ratine (exposure):
Medium.
Risk Considerations: Worker unreasonable risk
determination reflects the severity of the effects
associated with chronic exposures, even in the
presence of expected PPE. The high-end scenario
risk estimates indicate risk even when expected use
of PPE was considered (gloves PF = 10). Risk
estimates for the high-end acute exposures indicate
risk in the absence of PPE. While the chronic central
tendency scenario risk estimate indicates risk in the
absence of PPE, risk estimates for the central
tendency scenarios do not indicate risk (MOE = 291)
when expected use of PPE was considered (gloves
PF =10) (Table 4-12). EPA relied on data, models, or
a combination to estimate exposure and then
estimate risk from NMP for this condition of use.
Relevant factors that may generate uncertainties and
affect the risk calculations include representativeness
and age of the data for the condition of use, as well
as assumptions about glove use, glove effectiveness,
duration of contact with NMP, concentration of
NMP, and amount of skin surface contact with
NMP. The primary limitations of the exposure
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scenario inpuLs and models for tins condition of use
are in Section 2.4.1.2.4.
Estimated exposed population: 1.900 workers.
Processing
Incorporated
into articles
Other, including in Plastic
Product Manufacturing
Section 6(b)(4)(A) unreasonable risk determination
for processing N \ 1 lJ for incorporation into articles in
other sectors, including in plastic product
manufacturing:
- Does not present an unreasonable risk of injury to
health (workers, occupalional non-users).
1 \posure scenario with highest risk eslimale:
Repmduclixe effects from chronic inhalalion and
dermal exposure.
Benchmark \I()E = 30 for reproductive effects.
Risk Estimate: MOE = 143 with workers using
ylines (PF = 10) (high-end scenario) (Table 4-10).
S\ slemalic Review confidence ratine (hazard): Hiah.
S\ stematic Review confidence ratine (exposure):
Medium.
Risk Considerations: While the risk estimates for the
chronic central tendency and high-end scenarios
indicate risk in the absence of PPE, risk estimates for
the central tendency and high-end scenarios do not
indicate risk when expected use of PPE was
considered (gloves PF = 10) (Table 4-10). EPA
relied on data, models, or a combination to estimate
exposure and then estimate risk from NMP for this
condition of use. Relevant factors that may generate
uncertainties and affect the risk calculations include
representativeness and age of the data for the
condition of use, as well as assumptions about glove
use, glove effectiveness, duration of contact with
NMP, concentration of NMP, and amount of skin
surface contact with NMP. The primary limitations
of the exposure scenario inputs and models for this
condition of use are in Section 2.4.1.2.3.
Estimated exposed population: 5.400 workers.
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Processing
Repackaging
Wholesale and Retail Trade
Section 6(b)(4)(A) unreasonable risk determination
for processing of NMP for repackaging for
wholesale and retail trade:
-Does not present an unreasonable risk of injury to
health (workers, occupational non-users).
Exposure scenario with highest risk estimates:
Reproductive effects from chronic inhalation and
dermal exposure.
I)n\ er Benchmark: MOE - 3t> lor reproductive
el lecls.
Risk Lslimale \IOE = 25 with workers using gloves
(PF If)) (hiijh-end scenario) (Table 4-8).
Svslemalic Re\ lew confidence rating (hazard): Hiah.
S\ slemalic Rev lew confidence rating (exposure):
Medium
Risk Considerations: While the high-end scenario
risk eslimules indicate risk in the absence of PPE and
\\ hen expected use of PPE was considered (gloves
PI' = 10), given the uncertainties in the model, these
were not considered unreasonable risks (Table 4-8).
While the chronic central tendency scenario risk
estimate indicates risk in the absence of PPE, risk
estimates for the central tendency scenarios do not
indicate risk (MOE = 213) when expected use of
PPE was considered (gloves PF = 10) (Table 4-8).
EPA relied on data, models, or a combination to
estimate exposure and then estimate risk from NMP
for this condition of use. Relevant factors that may
generate uncertainties and affect the risk calculations
include representativeness and age of the data for the
condition of use, as well as assumptions about glove
use, glove effectiveness, duration of contact with
NMP, concentration of NMP, and amount of skin
surface contact with NMP. The primary limitations
of the exposure scenario inputs and models for this
condition of use are in Section 2.4.1.2.2.
Estimated exposed population: 1.100 workers.
Processing
Recycling
Recycling
Section 6(b)(4)(A) unreasonable risk determination
for processing - recvcling of NMP:
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-Docs not present an unreasonable risk of injur) Lo
health (workers, occupational non-users).
Exposure scenario with highest risk estimate:
Reproductive effects from chronic inhalation and
dermal exposure.
Benchmark: MOE = 3<> lor reproductive effects.
Risk Estimate: MOE = 43 \\ illi workers using aloves
(PF 5) (high-end scenario) (Table 4-3^).
S\ slcmatic Review confidence ralinu (hazard): High.
Svslcmalic Review confidence rating (exposure):
Medium.
Risk Considerations While the chronic hiah-end
scenario risk cslimalcs indicate risk in the absence of
PPIrisk cslimalcs lor these scenarios do not
mdicalc risk when use of PPE was considered
(glo\ cs PF 5). For this condition of use, EPA
expects glo\ cs PF = 20, due to the recycling of
solvents. For NMP, risks are not indicated with
gloves PF = 5. While the chronic central tendency
scenario risk estimate indicates risk in the absence of
PPE, risk estimates for the central tendency scenarios
do not indicate risk when expected use of PPE was
considered (gloves PF = 5) (Table 4-36). EPA relied
on data, models, or a combination to estimate
exposure and then estimate risk from NMP for this
condition of use. Relevant factors that may generate
uncertainties and affect the risk calculations include
representativeness and age of the data for the
condition of use, as well as assumptions about glove
use, glove effectiveness, duration of contact with
NMP, concentration of NMP, and amount of skin
surface contact with NMP. The primary limitations
of the exposure scenario inputs and models for this
condition of use are in Section 2.4.1.2.16.
Estimated exposed population: 200 workers.
Distribution
in
commerce
Distribution
in Commerce
Distribution in Commerce
Section 6(b)(4)(A) unreasonable risk determination
for distribution in commerce of NMP:
- Does not present an unreasonable risk of injury to
health (workers, occupational non-users)
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I nreasonable Risk Determination1
Risk Considerations: A quantitative evaluation of the
distribution of NMP was not included in the risk
evaluation because exposures and releases from
distribution were considered within each condition of
use.
Industrial
and
commercial
use
Paints and
coatings
Paint and coating removers
Adhesive removers
Section 6(b)(4)( A) unreasonable risk determination
for industrial and commercial use of NMP in paint
and coating removers and in adhesive removers:
-Presents an unreasonable risk of in jury to health
(workers).
- Docs not present an unreasonable risk of injury to
health (occupational-non users)
Unreasonable risk driver: Reproductive effects from
chronic inhalation and dermal exposure.
Dm er Benchmark MOI= 30 for reproductive
el'lee is
Risk Lslimales - Workers:
MOI!
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estimates for inhalation exposures and \ apor-
through-skin uptake indicate risk, the chronic central
tendency scenario risk estimate does not indicate
risk. In contrast to the worker risk estimates, which
include dermal exposure, the risk estimates for
occupational non-users use exclusively inhalation
and vapor-through skin exposures. (Table 4-37).
EPA relied on data, models, or a combination to
estimate exposure and then estimate risk from NMP
for this condition of use Rele\ ant factors that may
generate uncertainties and aflecl llie risk calculations
include representativeness and age of the data for the
condition of use. as well as assumptions about glove
use. glo\ e effectiveness, duration of contact with
NMP. concentration of NMP, and amount of skin
surface conlacl with NMP. Data sources did not
usually mdicale whether NMP exposure
concentrations were for occupational users or ONUs.
I'or inhalation and \ apor-through-skin exposures, if
U\\ cannot dislinguish ONU exposures from
workers. LPA assumes that ONUs are exposed to
lower air concentrations compared to workers
because they are expected to be located a greater
distance from the worker handling the NMP-
containing product. To account for those instances
where monitoring data or modeling did not
distinguish between worker and ONU inhalation
exposure estimates, EPA considered the central
tendency risk estimate when determining ONU risk.
(Table 4-37). The primary limitations of the
exposure scenario inputs and models for this
condition of use are in Section 2.4.1.2.6.
Estimated exposed population: 2.000.000 workers.
Industrial
and
commercial
use
Pamls and
coalings
Lacquers, stains, varnishes,
primers and floor finishes
Section 6(b)(4¥A) unreasonable risk determination
for industrial and commercial use of NMP in paint
and coatings (lacauers. stains, varnishes, primers and
floor finishes, and powder coatings, surface
preparation), in paint additives and coating additives
Powder coatings (surface
preparation)
not described bv other codes in several
manufacturing sectors, and in adhesives and sealants,
several tvpes:
- Presents an unreasonable risk of injury to
health (workers).
Paint
additives and
coating
additives not
Use in Computer and
Electronic Product
Manufacturing, Construction,
Fabricated Metal Product
Manufacturing, Machinery
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- Does no I present an unreasonable risk of injur) lo
health (occupational non-users).
Unreasonable risk driver: Reproductive effects from
chronic inhalation and dermal exposure.
Driver Benchmark: \l()f = 30 for reproductive
effects
Risk Insinuates: MOE = 12 uilh workers using
glo\es (lJF = 10) for spray, roll curiam, dip, or brush
applications (high-end scenarios) ( Table 4-14).
S\ slemalic Rex lew confidence rating (hazard): High.
described b\
other codes
Manufacturing, Oilier
Manufacturing, Paint and
Coating Manufacturing,
Primary Metal
Manufacturing,
Transportation Equipment
Manufacturing, Wholesale
and Retail Trade
Adhesives
and sealants
Adhesives and sealant
chemicals including binding
agents
Single component glues and
adhesives, including
lubricant adhesives
Two-component glues and
adhesives, including some
resins
Svslemalic Rex iew confidence rating (exposure):
Medium to High
Risk ( onsideralions W orker unreasonable risk
delemunalion rellecls the severity of the effects
associated \x ith chronic exposures, even in the
presence of expected PPE. The high-end scenario
risk estimates indicate risk even when expected use
of PPE was considered (gloves PF = 10). (Table 4-
14). Risk estimates for the central tendency scenarios
did not indicate risk in the absence of PPE (Table 4-
14). EPA relied on data, models, or a combination to
estimate exposure and then estimate risk from NMP
for this condition of use. Relevant factors that may
generate uncertainties and affect the risk calculations
include representativeness and age of the data for the
condition of use, as well as assumptions about glove
use, glove effectiveness, duration of contact with
NMP, concentration of NMP, and amount of skin
surface contact with NMP. The primary limitations
of the exposure scenario inputs and models for this
condition of use are in Section 2.4.1.2.7.
Estimated exposed population: 2.000.000 workers.
Industrial
and
commercial
use
Solvents (for
cleaning or
degreasing)
Use in Electrical Equipment,
Appliance and Component
Manufacturing
Section 6(b)(4)(A) unreasonable risk determination
for industrial and commercial use of NMP as a
solvent (for cleaning or degreasing) use in electrical
eauipment. appliance and component manufacturing
and for other uses in manufacturing lithium ion
batteries:
Other uses
Lithium ion batteries cd
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- Presents an unreasonable risk of injury to
health (workers).
- Does not present an unreasonable risk of injury to
health (occupational n on -users).
Unreasonable risk driver: Reproductive effects from
chronic inhalation and dermal exposure.
Driver Benchmark: MOE = 30 for reproductive
effects.
Risk Estimates (workers usiim ^lo\es (PF = 10).
(high-end scenario): container hand I mil: MOE = 6;
drum handling: MOE = 6; fab worker: MOE = 4;
maintenance: MOE = 4; truck unloading: MOE = 6;
waste iruck unloading: MOE = 7. (Table 4-28).
S\ stematic Re\ ie\\ confidence rating (hazard): High.
S\ slemalic Review confidence rating (exposure):
Medium in I ligh
Risk Considerations: For all workers, the worker
unreasonable risk determination reflects the severity
of the effects associated with chronic exposures,
even in the presence of expected PPE. The high-end
scenario risk estimates indicate risk even when
expected use of PPE was considered (gloves PF =
10). The chronic central tendency scenario risk
estimates indicate risk in the absence of PPE. The
chronic central tendency scenario risk estimates also
indicate risks with expected use of PPE for specific
activities (small container handling, virgin NMP
truck unloading and waste truck unloading) but not
for other activities (container handling drums, fab
workers, maintenance) (gloves PF = 10) (Table 4-
28). EPA relied on data, models, or a combination to
estimate exposure and then estimate risk from NMP
for this condition of use. Relevant factors that may
generate uncertainties and affect the risk calculations
include representativeness and age of the data for the
condition of use, as well as assumptions about glove
use, glove effectiveness, duration of contact with
NMP, concentration of NMP, and amount of skin
surface contact with NMP. The primary limitations
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I nroiisoiiiihle Risk Detenu million1
of the exposure scenario iiipuLs and models for Llns
condition of use are in Section 2.4.1.2.8.
Estimated exposed population: 660,000 workers^
Industrial
and
commercial
use
Ink, toner,
and colorant
products
Printer ink
Inks in writing equipment
Section 6(b)(4)(A) unreasonable risk determination
for industrial and commercial use of NMP in ink,
toner, and colorant products, including printer ink
and inks in writing euumment:
-Does not present an unreasonable risk of injury to
health (workers, occupalional non-users).
l\|iosure scenario with highest risk estimate:
Repmduclixe effects from chronic inhalation and
dermal exposure.
Benchmark \I()E = 30 for reproductive effects.
Risk Estimate \I()I! 48 with workers using gloves
(H; 5) (high-end scenario) (Table 4-16).
S\ sternalic Rex lew confidence rating (hazard): High.
Systematic Review confidence rating (exposure):
Medium to High.
Risk Considerations: While the high-end scenario
risk estimates for printing indicate risk in the absence
ofPPE, risk estimates for this scenario do not
indicate risk when expected use of PPE was
considered (gloves PF = 5). Risk estimates for the
central tendency scenarios did not indicate risk in the
absence ofPPE (Table 4-16). EPA relied on data,
models, or a combination to estimate exposure and
then estimate risk from NMP for this condition of
use. Relevant factors that may generate uncertainties
and affect the risk calculations include
representativeness and age of the data for the
condition of use, as well as assumptions about glove
use, glove effectiveness, duration of contact with
NMP, concentration of NMP, and amount of skin
surface contact with NMP. The primary limitations
of the exposure scenario inputs and models for this
condition of use are in Section 2.4.1.2.9.
Estimated exposed population: 53,000 workers.
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I nroiisoiiiihle Risk l)clcrniin;ili<)iii : i
Industrial
and
commercial
use
Processing
aids, specific
to petroleum
production
Petrochemical
Manufacturing
Section 6(b)(4)(A) unreasonable risk determination
for industrial and commercial use of NMP in
processing aids, specific to petroleum production in
petrochemical manufacturing, and other uses in oil
and gas drilling and pharmaceutical and medicine
manufacturing-
-Does not present an unreasonable risk of injury to
health (workers, occupational non-users).
Exposure scenario with hiuhcsl risk estimate:
Other uses
Other uses in Oil and Gas
Drilling, Extraction and
Support Activities
Pharmaceutical and
Medicine Manufacturing -
functional fluids (closed
systems)
Reproductive effects from chronic inhalation and
dermal exposure.
benchmark \I()L 30 for reproductive effects.
Risk 1 islimalc \IOE = 143 with workers using
gkncs (PI' In) (high-end scenario) (Table 4-10).
S\ slcmalic Rev lew confidence rating (hazard): High.
S\ slcmalic Review confidence rating (exposure):
Medium
Risk Considerations: While the risk estimates for the
chronic central tendency and high-end scenarios
indicate risk in the absence of PPE, risk estimates for
the central tendency and high-end scenarios do not
indicate risk when expected use of PPE was
considered (gloves PF = 10) (Table 4-10). EPA
relied on data, models, or a combination to estimate
exposure and then estimate risk from NMP for this
condition of use. Relevant factors that may generate
uncertainties and affect the risk calculations include
representativeness and age of the data for the
condition of use, as well as assumptions about glove
use, glove effectiveness, duration of contact with
NMP, concentration of NMP, and amount of skin
surface contact with NMP. The primary limitations
of the exposure scenario inputs and models for this
condition of use are in Section 2.4.1.2.3.
Estimated exposed population: 5.400 workers.
Industrial
and
commercial
use
Other uses
Soldering materials
Section 6(b)(4)(A) unreasonable risk determination
for industrial and commercial use of NMP as
soldering material:
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-Docs not present an unreasonable risk of injur) to
health (workers, occupational non-users).
Exposure scenario with highest risk estimate:
Reproductive effects from chronic inhalation and
dermal exposure.
Benchmark: MOE = 3d lor reproductive effects.
Risk Estimate: MOE = 270 w iill workers using
gloves (PF = 10) (high-end scenario) (Table 4-30).
S\ stcmatic Review confidence ratine (hazard): High.
Systematic Review confidence raliim (exposure):
Low to Medium.
Risk Considerations: While the high-end chronic
scenario risk estimate indicates risk in the absence of
PPL. risk estimates lor this scenario do not indicate
risk w hen expected use of PPE was considered
(glo\ cs PI' 10) (Table 4-30). EPA relied on data,
models, or a combination to estimate exposure and
then estimate risk from NMP for this condition of
use. Relevant factors that may generate uncertainties
and affect the risk calculations include
representativeness and age of the data for the
condition of use, as well as assumptions about glove
use, glove effectiveness, duration of contact with
NMP, concentration of NMP, and amount of skin
surface contact with NMP. The primary limitations
of the exposure scenario inputs and models for this
condition of use are in Section 2.4.1.2.10.
Estimated exposed population: 4,000,000 workers^
Industrial
and
commercial
use
Other uses
Anti-freeze and de-icing
products
Section 6(b)(4)(A) unreasonable risk determination
for industrial and commercial use of NMP in anti-
Automotive care products
Lubricants and greases
freeze and de-icing products, automotive care
products, and lubricants and greases:
- Presents an unreasonable risk of injury to
health (workers)
- Does not present an unreasonable risk of injury to
health (occupational non-users).
Unreasonable risk driver: Workers: Reproductive
effects from chronic inhalation and dermal exposure.
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Driver Benchmarks (workers and occupational non-
users): MOE = 30 for reproductive effects.
Risk Estimates: MOE = 10 with workers using
gloves (PF = 10) (high-end scenario) (Table 4-24).
Systematic Review confidence rating (hazard): High.
Systematic Review confidence ratine (exposure):
Medium.
Risk Considerations: The worker unreasonable risk
delermmation reflects the severity of the effects
associated with chronic exposures, even in the
presence of expected PPE for workers. For workers,
the chronic high-end scenario risk estimates for
inhalation and dermal exposures indicate risk even
w hen expected use of PPE was considered (gloves
PI' In) (Table 4-24). For workers, risk estimates
lor the central tendency scenarios did not indicate
risk in the absence of PPE (Table 4-24). For
occupational non-users (ONUs), while the chronic
high-end scenario risk estimates for inhalation
exposures and vapor-through-skin uptake indicates
risks, the chronic central tendency scenario risk
estimate does not indicate risk. In contrast to the
worker risk estimates, which include dermal
exposure, the risk estimates for occupational non-
users use exclusively inhalation and vapor-through-
skin exposures. (Table 4-37). EPA relied on data,
models, or a combination to estimate exposure and
then estimate risk from NMP for this condition of
use. Relevant factors that may generate uncertainties
and affect the risk calculations include
representativeness and age of the data for the
condition of use, as well as assumptions about glove
use, glove effectiveness, duration of contact with
NMP, concentration of NMP, and amount of skin
surface contact with NMP. Inhalation data sources
did not usually indicate whether NMP exposure
concentrations were for occupational users or ONUs.
For inhalation and vapor-through-skin exposures, if
EPA cannot distinguish ONU exposures from
workers, EPA assumes that ONUs are exposed to
lower air concentrations compared to workers
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I nreasonahle Risk Delerminalion1
because llie) are expected Lo be located a greater
distance from the worker handling the NMP-
containing product. To account for those instances
where monitoring data or modeling did not
distinguish between worker and ONU inhalation
exposure estimates. EPA considered the central
tendency risk estimate when determining ONU risk.
The primary limitations ol'the exposure scenario
inputs and models for this condition of use are in
Section 2.4.1.2.1 1.
Estimated exposed population wIO.ikki workers.
Industrial
and
commercial
use
Other uses
Metal products not covered
elsewhere
Section 6(b)(4)(A) unreasonable risk determination
for industrial and commercial use of NMP in metal
products and lubricants and lubricant additives,
including h\dionhilic coatings:
Lubricant and lubricant
additives, including
hydrophilic coatings
-Presents ;m unreasonable risk of injury to health
(workers).
- Does not present an unreasonable risk of injury to
health (occupational non-users).
Unreasonable risk driver: Reproductive effects from
chronic inhalation and dermal exposure.
Driver Benchmark: MOE = 30 for reproductive
effects.
Risk Estimate: MOE = 7 with workers using gloves
(PF =10) for spray, dip, or brush applications (high-
end scenarios) (Table 4-18).
Systematic Review confidence rating (hazard): Hiah.
Systematic Review confidence ratine (exposure):
Medium.
Risk Considerations: Worker unreasonable risk
determination reflects the severity of the effects
associated with chronic exposures, even in the
presence of expected PPE. The high-end scenario
risk estimates indicate risk even when expected use
of PPE was considered (gloves PF = 10). While the
chronic central tendency scenario risk estimate
indicates risk in the absence of PPE, risk estimates
for the central tendency scenarios do not indicate risk
when expected use of PPE was considered (gloves
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I nreasonahle Risk Delerminalion1
IM lU) ( Table 4-1IS). LPA relied on dala, models,
or a combination to estimate exposure and then
estimate risk from NMP for this condition of use.
Relevant factors that may generate uncertainties and
affect the risk calculations include representativeness
and age of the data for the condition of use, as well
as assumptions about glove use, glove effectiveness,
duration of contact with NMP, concentration of
NMP. and amount of skin surface contact with
NMP. The primary limitations of the exposure
scenario inputs and models lor ill is condition of use
are in Section 2.4.1.2.5.
Insinuated exposed population: 530.000 workers.
Industrial
and
commercial
use
Other uses
Laboratory chemicals
Section h(b)(4)(A) unreasonable risk determination
for industrial and commercial use of NMP as
laboratoi\ chemical:
- Presents an unreasonable risk of injury to
lieallh (workers).
- Does not present an unreasonable risk of injury to
lieallh (occupational non-users).
Unreasonable risk driver: Reproductive effects from
chronic inhalation and dermal exposure.
Driver Benchmark: MOE = 30 for reproductive
effects.
Risk Estimate: MOE = 6 with workers using aloves
(PF = 10) (high-end scenario) (Table 4-26).
Systematic Review confidence rating (hazard): Hiah.
Systematic Review confidence ratine (exposure):
Medium.
Risk Considerations: Worker unreasonable risk
determination reflects the severity of the effects
associated with chronic exposures, even in the
presence of expected PPE. The high-end scenario
risk estimates indicate risk even when expected use
of PPE was considered (gloves PF = 10). (Table 4-
26). While the chronic central tendency scenario risk
estimate indicates risk in the absence of PPE, risk
estimates for the central tendency scenarios do not
indicate risk when expected use of PPE was
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Condition of I so
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Category
Sub-Cate"or\
I nreasonahle Risk Determination1
considered (glo\es IM lU) (Table 4-2(>). LPA relied
on data, models, or a combination to estimate
exposure and then estimate risk from NMP for this
condition of use. Relevant factors that may generate
uncertainties and affect the risk calculations include
representativeness and age of the data for the
condition of use. as w ell as assumptions about glove
use, glove effectiveness, duration of contact with
NMP, concentration of W11\ and amount of skin
surface contact with NMP The primary limitations
ol'ihe exposure scenario inpuls and models for this
condition of use are in Section 2 4.1 2 12.
Lslimaled exposed population: 420.000 workers.
Industrial
and
commercial
use
Other uses
Cleaning and furniture care
products, including wood
cleaners, gasket remo\ ers
Section fMh)(4)(A) unreasonable risk determination
for nidusl rial and commercial use of NMP in
eleamng and I'uniiture care products, including wood
cleaners, gasket removers:
-Presents an unreasonable risk of injury to health
(workers).
- Does nol present an unreasonable risk of injury to
heallh (occupational non-users).
Unreasonable risk driver: Reproductive effects from
chronic inhalation and dermal exposure.
Driver Benchmark: MOE = 30 for reproductive
effects.
Risk Estimates: MOE = 6 for workers using gloves
(PF =10) for dip cleaning and spray/wipe cleaning
(high-end scenario) (Table 4-22).
Systematic Review confidence rating (hazard): High.
Systematic Review confidence rating (exposure):
Medium to High.
Risk Considerations: Worker unreasonable risk
determination reflects the severity of the effects
associated with chronic exposures, even in the
presence of expected PPE. The high-end scenario
risk estimates indicate risk even when expected use
of PPE was considered (gloves PF =10). (Table 4-
22). The chronic central tendency risk estimate for
dip cleaning and spray/wipe cleaning do not indicate
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risk when expected use of PPL was considered
(gloves PF = 10) (Table 4-22). EPA relied on data,
models, or a combination to estimate exposure and
then estimate risk from NMP for this condition of
use. Relevant factors that may generate uncertainties
and affect the risk calculations include
representativeness and age of the data for the
condition of use. as well as assumptions about glove
use, glove effectiveness, duration of contact with
NMP, concentration of \\ll\ and amount of skin
surface contact with NMP. The primary limitations
of the exposure scenario inpuls and models for this
condilion of use are in Section 2 4 12 13
Lslimaled exposed population: 190.000 workers.
Industrial
and
commercial
use
Other uses
Fertilizer and other
agricultural chemical
manufacturing - processing
aids and solvenis
Secuon Mb)(4)(\) unreasonable risk determination
lor industrial and commercial use of NMP in
fertilizer and oilier agricultural chemical
manufacturing
-Does nol present an unreasonable risk of injury to
health (workers, occupational non-users).
Exposure scenario with highest risk estimate:
Reproductive effects from chronic inhalation and
dermal exposure.
Benchmark: MOE = 30 for reproductive effects.
Risk Estimate: MOE = 38 for workers using aloves
(PF = 5) (high-end scenario) (Table 4-32).
Systematic Review confidence rating (hazard): Hiah.
Systematic Review confidence ratine (exposure):
Medium.
Risk Considerations: While the hi eh-end scenario
risk estimates indicate risk in the absence of PPE,
risk estimates for these scenarios do not indicate risk
when expected use of PPE was considered (gloves
PF = 5). Risk estimates for the central tendency
scenarios did not indicate risk in the absence of PPE
(Table 4-32). EPA relied on data, models, or a
combination to estimate exposure and then estimate
risk from NMP for this condition of use. Relevant
factors that may generate uncertainties and affect the
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risk calculations include represenlaln eness and age
of the data for the condition of use, as well as
assumptions about glove use, glove effectiveness,
duration of contact with NMP, concentration of
NMP, and amount of skin surface contact with
NMP. The primary limitations of the exposure
scenario inputs and models for this condition of use
are in Section 2.4.1.2.14.
Estimated exposed DODiilalion. 1.300.000 workers.
Industrial
and
commercial
use
Other uses
Wood preservatives
Section 6(b)(4)(A) unreasonable risk determination
for industrial and commercial use of NMP as a wood
preservative:
-Does not present an unreasonable risk of injury to
heallh (workers, occupational non-users).
r\nosure scenario with highest risk estimate:
Re|iroducti\ e el'l'ecls from chronic inhalation and
dermal exposure
benchmark \l()f 30 for reproductive effects.
Risk Estimate: MOE = 52 for workers without
gloves (high-end scenario) (Table 4-34).
Systematic Review confidence ratine (hazard): High.
Systematic Review confidence rating (exposure):
Medium.
Risk Considerations: Risk estimates for all acute and
chronic inhalation and dermal exposures (high-end
and central tendency) do not indicate risk (Table 4-
33 and Table 4-34). EPA relied on data, models, or a
combination to estimate exposure and then estimate
risk from NMP for this condition of use. Relevant
factors that may generate uncertainties and affect the
risk calculations include representativeness and age
of the data for the condition of use, as well as
assumptions about glove use, glove effectiveness,
duration of contact with NMP, concentration of
NMP, and amount of skin surface contact with
NMP. The primary limitations of the exposure
scenario inputs and models for this condition of use
are in Section 2.4.1.2.15.
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Insinuated exposed population. ^XU.UUU workers.
Consumer
use
Paints and
coatings
Paint and coating removers
Section 6(b)(4)(A) unreasonable risk determination
for consumer use of NMP in paint and coating
removers:
-Presents an mi reasonable risk of injury to health
(consumers).
Unreasonable risk dmer l)e\elopmcntal adverse
effects from acute inhalation and dermal exposure.
I)n\ er Benchmark: MOE = 3d lor developmental
el lecls.
Risk 1 isiinuik' \IOE = 22 (hieh intensity use) (Table
4-44)
S\ steniatie Re\ lew confidence ratine (hazard): High.
S\ steniatie Re\ lew confidence rating (exposure):
Medium to 1 ligh.
Risk Considerations: Consumer unreasonable risk
determination reflects the severity of the effects
associated with acute exposures. The high intensity
use scenario risk estimates indicate risk. Risk
estimates for the medium intensity use scenarios of
acute inhalation and dermal exposures did not
indicate risk. (Table 4-44). EPA relied on data,
models, or a combination to estimate exposure and
then estimate risk from NMP for this condition of
use. Relevant factors that may generate uncertainties
and affect the risk calculations include
representativeness and age of the data for the
condition of use, as well as assumptions about
duration of contact with NMP, concentration of
NMP, and amount of skin surface contact with
NMP. The primary limitations of the exposure
scenario inputs and models for Consumer Conditions
of Use are in Section 2.4.2.
Estimated exposed populations: There is uncertainty
regarding the number of consumers exposed under
the consumer conditions of use and the nature and
extent of the consumer use of products containing
NMP. EPA provides information in Table 2-69 on
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I nroiisoiiiihle Risk Dclcrmiiiiilion1
VMI'-conluining consumer products used i'or the
exposure assessment.
Consumer
use
Paints and
coatings
Adhesive removers
Section 6(b)(4)(A) unreasonable risk determination
for consumer use of NMP in adhesive removers:
-Does not present an unreasonable risk of injury to
health (consumers and bystanders to consumer use).
Exposure scenario will) highest:risk estimate:
Developmental adverse el'lecls I'rom acute inhalation
and dermal exposure.
ISenclimark: MOE = 30 for de\ elopmenlal effects.
Risk Lslimale \IOE = 36 (high mlensih use) (Table
4-»)
S\ sternal ic Rex lexx confidence rating (hazard): High.
S\ slematic Rex lexx confidence rating (exposure):
Medium in I ligh.
Risk Considerations: Risk estimates for all acute
inhalation and dermal exposures do not indicate risk
(Table 4-39). EPA relied on data, models, or a
combination to estimate exposure and then estimate
risk from NMP for this condition of use. Relevant
factors that may generate uncertainties and affect the
risk calculations include representativeness and age
of the data for the condition of use, as well as
assumptions about duration of contact with NMP,
concentration of NMP, and amount of skin surface
contact with NMP. The primary limitations of the
exposure scenario inputs and models for Consumer
Conditions of Use are in Section 2.4.2.
Estimated exposed populations: There is uncertainty
regarding the number of consumers exposed under
the consumer conditions of use and the nature and
extent of the consumer use of products containing
NMP. EPA provides information in Table 2-69 on
NMP-containing consumer products used for the
exposure assessment.
Consumer
use
Paints and
coatings
Lacquers, stains, varnishes,
primers and floor finishes
Section 6(b)(4)(A) unreasonable risk determination
for consumer use of NMP in lacquers, stains,
varnishes, primers and floor finishes:
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-Docs not present an unreasonable risk of injur) lo
health (consumers and bystanders to consumer use).
Exposure scenario with highest risk estimate:
Developmental adverse effects from acute inhalation
and dermal exposure.
Benchmark: MOE = 30 for developmental effects.
Risk Estimate: MOE = 1 1 1 (hilj li intensity use)
(Table 4-43).
Systematic Review confidence ralmu (ha/a id): High.
Systematic Review confidence ralnm (exposure):
Medium to High.
Risk Consideralions: Risk estimates for all acute
inhalalion ;uid dermal exposures do not indicate risk
(TaMc 4-43) EPA relied on data, models, or a
comlnnalion to estimate exposure and then estimate
risk from \\1P for this condition of use. Relevant
factors thai max generate uncertainties and affect the
risk calculations include representativeness and age
of the data for the condition of use, as well as
assumptions about duration of contact with NMP,
concentration of NMP, and amount of skin surface
contact with NMP. The primary limitations of the
exposure scenario inputs and models for Consumer
Conditions of Use are in Section 2.4.2.
Estimated exposed populations: There is uncertainty
regarding the number of consumers exposed under
the consumer conditions of use and the nature and
extent of the consumer use of products containing
NMP. EPA provides information in Table 2-69 on
NMP-containing consumer products used for the
exposure assessment.
Consumer
use
Paint
additives and
coating
additives not
described by
other codes
Paints and Arts and Crafts
Paints
Section 6(b)(4)(A) unreasonable risk determination
for consumer use of NMP in paint additives and
coating additives not described bv other codes,
paints, and arts and crafts paints:
- Does not present an unreasonable risk of injury to
health (consumers and bystanders to consumer use).
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Exposure scenario wilh hiahesl risk eslimule.
Developmental adverse effects from acute inhalation
and dermal exposure.
Benchmark: MOE = 30 for developmental effects.
Risk Estimate: MOE = 152 (paints, hiah intensitv
use) (Table 4-42).
Systematic Review confidence rutins (hazard): Hiah.
S\ slemutic Review confidence rulin-j (exposure):
Medium to High
Risk ( onsiderulions: Risk estimates for all acute
inhalalion und dermal exposures do not indicate risk
(Table 4-42) LP A relied on data, models, or a
combination in estimate exposure and then estimate
risk from WIP lor this condition of use. Relevant
luclors lliul ma\ generate uncertainties and affect the
risk calculutions include representativeness and age
of llie dalu for the condition of use, as well as
assumptions about duration of contact with NMP,
concentration of NMP, and amount of skin surface
contact with NMP. The primary limitations of the
exposure scenario inputs and models for Consumer
Conditions of Use are in Section 2.4.2.
Estimated exposed populations: There is uncertainty
regarding the number of consumers exposed under
the consumer conditions of use and the nature and
extent of the consumer use of products containing
NMP. EPA provides information in Table 2-69 on
NMP-containing consumer products used for the
exposure assessment.
Consumer
use
Adhesi\es
and sealunls
Single component glues and
adhesives, including
lubricant adhesives
Section 6(b)(4)(A) unreasonable risk determination
for consumer use of NMP as adhesive and sealant,
sinale component alues and adhesives. includina
Two-component glues and
adhesives, including some
resins
lubricant adhesives and two-component alues and
adhesives. includina some resins:
- Does not present an unreasonable risk of injury to
health (consumers and bystanders to consumer use).
Exposure scenario with hiahest risk estimate:
Developmental adverse effects from acute inhalation
and dermal exposure.
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Benchmark: MOE = 30 for developmental effects.
Risk Estimate: MOE 38 (adhesives. hiah intensity
use) (Table 4-38)
Systematic Re\ lew confidence ratine (hazard): Hiah.
Systematic Re\ ie\\ confidence ratina (exposure):
Medium to High.
Risk Considerations: Risk eslimales lor all acute
inhalation and dermal exposures do nol indicate risk
(Table 4-38). EPA relied on data, models, or a
combinalion to estimate exposure and then estimate
risk from WIP lor this condition of use. Relevant
factors thai ma\ generate uncertainties and affect the
risk calculations include representativeness and age
of llie data for the condition of use, as well as
assumptions about duration of contact with NMP,
concentration of NMP. and amount of skin surface
contact with NMP. The primary limitations of the
exposure scenario inputs and models for Consumer
Conditions of Use are in Section 2.4.2.
Estimated exposed populations: There is uncertainty
regarding the number of consumers exposed under
the consumer conditions of use and the nature and
extent of the consumer use of products containing
NMP. EPA provides information in Table 2-69 on
NMP-containing consumer products used for the
exposure assessment.
Consume]'
use
Oilier uses
Aulomotive care products
Section 6(b)(4)(A) unreasonable risk determination
for consumer use. other use as automotive care
products of NMP:
- Does not present an unreasonable risk of injury to
health (consumers and bystanders to consumer use).
Exposure scenario with hiahest risk estimate:
Developmental adverse effects from acute inhalation
and dermal exposure.
Benchmark: MOE = 30 for developmental effects.
Risk Estimate: MOE = 50 (auto interior liauid
cleaner, high intensity use) (Table 4-40).
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Systematic Review confidence ratine (hazard): High.
Systematic Review confidence rating (exposure):
Medium to High.
Risk Considers inns Risk estimates for all acute
inhalation and dermal exposures do not indicate risk
(Table 4-40). EPA relied on data, models, or a
combination to estimate exposure and then estimate
risk from NMP for this condition of use. Relevant
factors that may generate uncerlainlies and affect the
risk calculations include representativeness and age
of the data for the condition of use. as well as
assumptions about duration of contact with NMP,
concentration of NMP, and amount of skin surface
contact w ilh \ \ l P. The primary limitations of the
exposure scenario inputs and models for Consumer
Conditions of Lse are in Section 2.4.2.
Lslimaled exposed populations: There is uncertainty
regarding llie number of consumers exposed under
the consumer conditions of use and the nature and
extent of the consumer use of products containing
NMP. EPA provides information in Table 2-69 on
NMP-containing consumer products used for the
exposure assessment.
Consumer
use
Oilier uses
( leaning and I'ui niLure care
pnidncls. including wood
cleaners. Liaskcl removers
Section 6(b)(4)(A) unreasonable risk determination
for consumer use of NMP in other uses as cleaning
and furniture care products, including wood cleaners,
aasket removers:
- Presents an unreasonable risk of injury to
health (consumers).
Unreasonable risk driver: Developmental adverse
effects from acute inhalation and dermal exposure.
Driver Benchmark: MOE = 30 for developmental
effects.
Risk Estimate: MOE = 16 (clcaners/deereasers. high
intensity use); MOE =13 (engine cleaner/degreaser,
high intensity use) (Table 4-41).
Systematic Review confidence rating (hazard): High.
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CsiU'Sorv
tii of i so
Suh-CsiU'Korv
I nroiisoiiiihle Risk Dclcrminjilion1
S\ sLemalic Rewew coiiildence rulum (exposure).
Medium to High.
Risk Considerations: Consumer unreasonable risk
determination reflects the severity of the effects
associated with acute exposures. The high intensity
use scenario risk estimates indicate risk. Risk
estimates for the medium intensity use scenarios of
acute inhalation and dermal exposures did not
indicate risk. (Table 4-41). UW relied on data,
models, or a combination to eslimale exposure and
llien estimate risk from NMP lor this condition of
use Relevant factors that may generate uncertainties
and affect the risk calculations include
represenlativeness and age of the data for the
condition of use. as well as assumptions about
duration of conlact with NMP, concentration of
\\ll\ and amount of skin surface contact with
WIP The primary limitations of the exposure
scenario inputs and models for Consumer Conditions
of I se are in Section 2.4.2.
Estimated exposed populations: There is uncertainty
regarding the number of consumers exposed under
the consumer conditions of use and the nature and
extent of the consumer use of products containing
NMP. EPA provides information in Table 2-69 on
NMP-containing consumer products used for the
exposure assessment.
Consumer
use
Oilier uses
Lubricant and lubricant
addili\os. including
h\ druplii lie coatings
Section 6(b)(4)(A) unreasonable risk determination
for consumer use of NMP in other uses as lubricant
and lubricant additives, including hvdrophilic
coatings:
- Does not present an unreasonable risk of injury to
health (consumers and bystanders to consumer use).
Exposure scenario with highest risk estimate:
Developmental adverse effects from acute inhalation
and dermal exposure.
Benchmark: MOE = 30 for developmental effects.
Risk Estimate: MOE = 76 (sprav lubricant, high
intensity use) (Table 4-41).
Systematic Review confidence rating (hazard): High.
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Condition of I so
Life Cycle
Slsi«e
CsHc«»orv
Suh-CsiU'Korv
I nroiisoiiiihle Risk l)clcrniin;ili<)iii : i
Systematic Review confidence rating (exposure):
Medium to High.
Risk Considerations: Risk estimates for all acute
inhalation and dermal exposures do not indicate risk
(Table 4-41). EPA relied on data, models, or a
combination to estimate exposure and then estimate
risk from NMP for this condition of use. Relevant
factors that may generate uncertainties and affect the
risk calculations include representativeness and age
of the data forthe condition of use. as well as
assumptions about duration of contact with NMP,
concentration of NMP, and amount of skin surface
conlacl with NMP. The primary limitations of the
exposure scenario inputs and models for Consumer
Conditions of I se are in Section 2.4.2.
Intimated e\nosed nonulations: There is uncertainty
regarding ihe nunilvr ol'consumers exposed under
llie consumer conditions of use and the nature and
e\lenl of ihe consumer use of products containing
NMP. EPA provides information in Table 2-69 on
N MP-containing consumer products used for the
exposure assessment.
Disposal
Disposal
Industrial |ne-liealment
Section 6(b)(4)(A) unreasonable risk determination
for disposal of NMP:
- Does not present an unreasonable risk of injury to
health (workers, occupational non-users).
Exposure scenario with highest risk estimate:
Developmental adverse effects or reproductive
effects from chronic inhalation and dermal exposure.
Benchmark: MOE = 30 for developmental effects.
Industrial wastewater
treatment
PuMicK owned treatment
works (POTW )
Risk Estimate: MOE = 43 with workers using gloves
(PF = 5) (high-end scenario) (Table 4-36).
Systematic Review confidence ratine (hazard): High.
I nderground injection
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C ondition of I so
Life Cycle
Slsi«e
CsiU'Sorv
Suh-CsiU'Korv
I nroiisoiiiihle Risk l)clcniiin;ilioni : i
Landfill (municipal,
hazardous or other land
disposal)
S\ slemalic Rc\ lew confidence ralum (exposure).
Medium to High.
Risk Considerations: While the risk estimates for the
central tendency and high-end scenarios indicate risk
in the absence of PPE. risk estimates for these
scenarios do not indicate risk when expected use of
PPE was considered (glmcs PF=5). (Table 4-35 and
Table 4-36). EPA relied on data, models, or a
combination to estimate exposure and then estimate
risk from NMP for this condition of use. Relevant
factors that may generate uncertainties and affect the
risk calculations include representativeness and age
of the data for the condition of use. as well as
assumptions about glove use, glove effectiveness,
duration of contact with NMP, concentration of
NMP. and amount of skin surface contact with
\\ll\ The primary limitations of the exposure
scenario inputs and models for this condition of use
are in Section 2.4.1.2.16.
Insinuated exposed population: 200 workers.
Emissions to air
Incinerators (municipal and
hazardous waste)
1 EPA expects there is compliance w illi federal and state laws, such as worker protection standards, unless case-
specific facts indicate otlicru ise. and therefore existing OSHA regulations for worker protection and hazard
communication will result in use of appropriate PPE consistent with the applicable SDSs in a manner adequate to
protect them.
2 EPA recognizes that it may not lie realistic In assume PPE is not worn in workplaces with higher end exposures
or that PPE is ineffective. This is a health protective assumption EPA incorporated into the estimates for the high-
end exposure scenario
3 For many 01 !Ss. ihe high-end surface area assumption of contact over the full area of two hands likely
overestimates exposures
6896
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PEER REVIEW DRAFT, DO NOT CITE OR QUOTE
U.S. EPA. (2017d). Scope of the risk evaluation for N-Methylpyrrolidone (2-Pyrrolidinone, 1-Methyl-).
CASRN: 872-50-4 [EPA Report], (EPA-740-R1-7005).
https://www.epa.gov/sites/production/files/2i 'documents/nmp scope 6-22.-17 O.pdf
U.S. EPA. (2017e). Strategy for conducting literature searches for N-Methylpyrrolidone (NMP):
Supplemental document to the TSCA Scope Document. CASRN: 872-50-4 [EPA Report], (EPA-
740-R1-7005). https://www.epa. gov/sites/production/files/^
06/documents/nmp lit search strategy 053017 O.pdf
L (2017f). Toxics Release Inventory (TRI), reporting year 2015. Retrieved from
ta-and-tools
U.S. EPA. (2018a). Application of systematic review in TSCA risk evaluations. (740-P1-8001).
Washington, DC: U.S. Environmental Protection Agency, Office of Chemical Safety and
Pollution Prevention. https://www.epa.gov/sites/productioii/files/20M
U.S. EPA. (2018c). Problem formulation of the risk evaluation for n-methylp\ noli done (2-
pyrrolidinone, 1-methyl-). (EPA-740-R1-7015). Washington, DC: Office of Chemical Safety and
Pollution Prevention, United States Environmental Protection Agency.
https://www.epa.gov/sites/production/files/2018-06/d^-nment pf05-. ;
U.S. EPA. (2018d). Strategy for assessing data quality in TSCA risk evaluations. Washington DC: U.S.
Environmental Protection Agency, Office of Pollution Pre\ cut ion and Toxics.
U.S. EPA. (2019a). Draft risk evaluation for N-methyl-2-pyrrolidone Systematic review supplemental
file: data quality evaluation of physical-chemical properties studies. Washington, D.C.: U.S.
Environmental Protection Agency. Office of Chemical Safety and Pollution Prevention.
U.S. EPA. (2019b). Draft Risk Evaluation for N-Methylpyrrolidone, Supplemental Information on
Consumer Exposure Assessment. (Docket EPA-HQ-OPPT-2019-0236).
U.S. EPA. (2019c). Draft Risk I a al nation for N-M ethyl pyrrol i done. Supplemental Information on
Consumer Exposure Assessment, Consumer Exposure Model Input Parameters. Docket EPA-
HQ-OPPT-2019-0236. (I P \-l IQ-OPPT-2019-0236).
U.S. EPA. (2019d). Draft Risk l-\ al nation for N-Methylpyrrolidone, Supplemental Information on
Consumer Exposure Assessment. Consumer l-xposure Model Outputs. Docket EPA-HQ-OPPT-
2019-0236. (EPA-HQ-OPPT-Zi) 11)-<)230)
U.S.TTi" (2019e). Draft Risk Evaluation for N-M ethyl pyrrol i done. Supplemental Information on
Consumer Exposure Assessment. PBPK Model Inputs Outputs. Docket EPA-HQ-OPPT-2019-
D230 (EPA-HQ-OPPT-2019-D230).
U.S. .u,i i (2<) 1 l)f). Draft Risk Evaluation for N-Methylpyrrolidone, Supplemental Information on
Human I lealth Benchmark Dose Modeling. (Docket EPA-HQ-OPPT-2019-0236).
U.S. EPA. (201 %) Draft Risk Evaluation for N-Methylpyrrolidone, Supplemental Information on
Occupational I Exposure Assessment. (Docket EPA-HQ-OPPT-2019-0236).
U.S. EPA. (2019h). Draft Risk Evaluation for N-Methylpyrrolidone, Systematic Review Supplemental
File: Data Quality Evaluation of Consumer and General Population Studies. (Docket EPA-HQ-
OPPT-2019-023 6).
U.S. EPA. (2019i). Draft Risk Evaluation for N-Methylpyrrolidone, Systematic Review Supplemental
File: Data Quality Evaluation of Environmental Fate and Transport Studies. (Docket EPA-HQ-
OPPT-2019-023 6).
U.S. EPA. (2019j). Draft Risk Evaluation for N-Methylpyrrolidone, Systematic Review Supplemental
File: Data Quality Evaluation of Environmental Hazard Studies. (Docket EPA-HQ-OPPT-2019-
0236).
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7440
7441
7442
7443
7444
7445
7446
7447
7448
7449
7450
7451
7452
7453
7454
7455
7456
7457
7458
7459
7460
7461
7462
7463
7464
7465
7466
7467
7468
7469
7470
7471
7472
7473
7474
7475
7476
7477
7478
7479
7480
7481
PEER REVIEW DRAFT, DO NOT CITE OR QUOTE
U.S. EPA. (2019k). Draft Risk Evaluation for N-Methylpyrrolidone, Systematic Review Supplemental
File: Data Quality Evaluation of Environmental Release and Occupational Exposure Data.
(Docket EP A-HQ-OPPT-2019-023 6).
U.S. EPA. (20191). Draft Risk Evaluation for N-Methylpyrrolidone, Systematic Review Supplemental
File: Data Quality Evaluation of Environmental Release and Occupational Exposure Data -
Common Sources. (Docket EPA-HQ-OPPT-2019-0236).
(2019m). Draft Risk Evaluation for N-Methylpyrrolidone, Systematic Review Supplemental
File: Data Quality Evaluation of Human Health Studies - Animal Studies. (Docket EPA-HQ-
OPPT-2019-023 6).
(2019n). Draft Risk Evaluation for N-Methylpyrrolidone, Systematic Review Supplemental
File: Data Quality Evaluation of Human Health Studies - Epidemiological Studies. (Docket
EPA-HQ-OPPT-2019-023 6).
U.S. EPA. (2019o). Risk Evaluation for N - M et hy 1 pyrrolidone (2-Pyrrolidinone. I -Methyl-) Systematic
Review Supplemental File: Data Quality Evaluation of Environmental Releases and
Occupational Exposure Common Sources.
U.S. EPA. (2019p). Risk Evaluation for N-Methylpyrrolidone (2-Pyrrolidinone, 1 -Methyl-) Systematic
Review Supplemental File: Data Quality Evaluation of Environmental Releases and
Occupational Exposure Data.
(2019q). Risk Evaluation for N-Methylpyrrolidone (2-l\ n olidinone, 1 Methyl-) (NMP),
Supplemental Excel File on Occupational Risk Calculations. (Docket EPA-HQ-OPPT-2019-
0236).
(2019r). Risk Evaluation for N-M ethyl pyrrol i done (2-Pynolidinone, 1 Methyl-) (NMP),
Supplemental Information on Occupational Exposure Assessment.
(2019s). Risk Evaluation for N-Methylpyrrolidone, Systematic Review Supplemental File:
Data Extraction Tables for Epidemiological Studies. (Docket EPA-HQ-OPPT-2019-0236). U.S.
Environmental Protection Agency :: U.S. EPA.
(2019t). Systematic Review Supplemental File: Updates to the Data Quality Criteria for
Epidemiological Studies. (Docket l-P V-HQ-OPPT-2019-0236).
Ursin. €:, Hansen. CM; Van Dvk. :ensen. I J; Ebbehoei. J. (1995). Permeability of
commercial solvents through li\ ing human skin Am Ind Hyg Assoc J 56: 651-660.
tr"-- "dx.doi.orr" " 1 ""Q/i jhzqi iyp91016665
van Raai lM; Janst Pi
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7482 Xiaofei. E; Wada. Y; Nozaki. J; Miyauchi. H; Tanaka. S; Seki. Y; Koizumi. A. (2000). A linear
7483 pharmacokinetic model predicts usefulness of N-methyl-2-pyrrolidone (NMP) in plasma or urine
7484 as a biomarker for biological monitoring for NMP exposure. J Occup Health 42: 321-327.
7485
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7486 APPENDICES
7487
7488 Appendix A REGULATORY HISTORY
7489
7490 A.l Federal Laws and Regulations
7491
7492 Table Apx A-l. Federal Laws and Regulations
Statutes/Regulations
Description of Authority/Regulation
Description of Regulation
EPA Regulations
Toxic Substances
Control Act (TSCA) -
Section 6(a)
If EPA evaluates the risk of a chemical
substance, in accordance with TSCA
Section 6(b)(A), and concludes that the
manufacture (including import),
processing, distribution in commerce,
disposal of such chemical substance, or
any combination of these acli\ ilies,
presents an unreasonable risk of injury to
human health or the environment, then
EPA shall, by rule, take one or more of
the actions described in TSCA Section
6(a)( 1)-(7) to ensure the chemical
substance no longer presents an
unreasonable risk
Proposed rule (82 1 R 7464)
regulating NMP uses in paint and
coating remo\al
Toxic Substances
Control Act (TSCA)
Section (>(h)
Directs F.IW to promulgate regulations
to establish processes for prioritizing
chemical substances and conducting risk
evaluations on priority chemical
substances In the meantime, EPA was
required to identify and begin risk
evaluations on 10 chemical substances
drawn from the 2014 update of the
TSCA Work Plan for Chemical
Assessments.
NMP is on the initial list of 10
chemical substances to be
evaluated for unreasonable risk of
injury to health or the
environment (81 FR 91927,
December 19, 2016)
Toxic Substances
Control Act (TSCA) -
Section8(a)
The TSCA section 8(a) Chemical Data
Reporting (CDR) Rule requires
manufacturers (including importers) to
give EPA basic exposure-related
information on the types, quantities and
uses of chemical substances produced
NMP manufacturing, importing,
processing and use information is
reported under the Chemical Data
Reporting (CDR) rule (76 FR
50816, August 16, 2011).
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SlsiliiU's/Ucgiihilions
Description of Aiilhorily/Ucgiihilion
Description of Ucgiihilion
domestically and imported into the US.
Toxic Substances
Control Act (TSCA) -
Section8(b)
EPA must compile, keep current and
publish a list (the TSCA Inventory) of
each chemical substance manufactured,
processed, or imported in the United
States.
NMP was on the initial TSCA
Inventory and therefore was not
subject to EPA's new chemicals
review process (60 FR 16309,
March 29, 1995).
Toxic Substances
Control Act (TSCA) -
Section 8(e)
Manufacturers (including importers),
processors and distributors must
immediately notify EPA if they obtain
information that supports the conclusion
that a chemical substance or mixture
presents a substantial risk of injury to
health or the environment.
Se\en notifications of substantial
risk (Section 8(e)) received (2007
- 2010) (I S I-PA, ChemView.
Accessed April 13,2017).
Toxic Substances
Control Act (TSCA) -
Section 4
Provides EPA with authority to issue
rules and orders requiring manufacturers
(including importers) and processors to
test chemical substances and mixtures.
Six submissions from a test rule
(Section 4) received in the mid-
N90s. (US EPA, ChemView.
Accessed April 13, 2017).
Emergency Planning and
Community Right-To-
Know Act (EPCRA) -
Section 313
Requires annual reporting from facilities
in specific industry sectors that employ
11") or more full time equivalent
employees and that manufacture,
process, or otherwise use a TRl-listed
chemical in quantities above threshold
le\els A facility that meets reporting
requirements must submit a reporting
lorm for each chemical for which it
triggered reporting, providing data
across a \ ariely of categories, including
activities and uses of the chemical,
releases and other waste management
(e.g., quantities recycled, treated,
combusted) and pollution prevention
activities (under section 6607 of the
Pollution Prevention Act). This data
includes on-site and off-site data as well
as multimedia data (i.e., air, land and
water).
NMP is a listed substance subject
to reporting requirements under
40 CFR 372.65 effective as of
January 1, 1995.
Federal Food, Drug and
Cosmetic Act (FFDCA)
- Section 408
FFDCA governs the allowable residues
of pesticides in food. Section 408 of the
FFDCA provides EPA with the authority
to set tolerances (rules that establish
NMP is currently approved for
use as a solvent and co-solvent
inert ingredient in pesticide
formulations for both food and
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SlsiliiU's/Ucgiihilions
Description of Aiilhorily/Ucgiihilion
Description of Ucgiihilion
maximum allowable residue limits), or
exemptions from the requirement of a
tolerance, for all residues of a pesticide
(including both active and inert
ingredients) that are in or on food. Prior
to issuing a tolerance or exemption from
tolerance, EPA must determine that the
tolerance or exemption is "safe."
Sections 408(b) and (c) of the FFDCA
define "safe" to mean the Agency has a
reasonable certainty that no harm will
result from aggregate exposures to the
pesticide residue, including all dietary
exposure and all other exposure (e.g.,
non-occupational exposures) for which
there is reliable information. Pesticide
tolerances or exemptions from tolerance
that do not meet the FFDCA safety
standard are subject to revocation. Tn the
absence of a tolerance or an exemption
from tolerance, a food containing a
pesticide residue is considered
adulterated and may not be distributed in
interstate commerce.
non-food uses and is exempt from
the requirements of a tolerance
limit (40 CFR Part 180.920).
Clean Air Act (CA A)
Section 111 (b)
Requires I -PA to establish new source
performance standards (NSPS) for any
category of new or modified stationary
sources that F.PA determines causes, or
contributes significantly to, air pollution
u hich may reasonably be anticipated to
endanger public health or welfare. The
standards are based on the degree of
emission limitation achievable through
the application of the best system of
emission reduction which (considering
the cost of achieving reductions and non-
air quality health and environmental
impacts and energy requirements) EPA
determines has been adequately
demonstrated.
NMP is subject to Clean Air Act
Section 111 Standards of
Performance for New Stationary
Sources of Air Pollutants for
VOC emissions from synthetic
organic chemical manufacturing
industry distillation operations
(40 CFR Part 60, subpart NNN)
and reactor processes (40 CFR
Part 60, Subpart RRR).
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Maliilcs/Ucgulalions
Description of Aiilhorily/Ucgulalion
Description of Regulation
Clean Air Act (CAA) -
Section 183(e)
Section 183(e) requires EPA to list the
categories of consumer and commercial
products that account for at least 80
percent of all VOC emissions in areas
that violate the National Ambient Air
Quality Standards for ozone and to issue
standards for these categories that
require "best available controls." In lieu
of regulations, EPA may issue control
techniques guidelines if the guidelines
are determined to be substantial l\ as
effective as regulations.
NMP is listed under the National
Volatile Organic Compound
Emission Standards for Aerosol
Coatings (40 CFR part 59,
subpart E).
Clean Air Act (CAA) -
Section 612
Under Section 612 of the Clean Air Act
(CAA), EPA's Significant New
Alternatives Policy (SNAP) program
reviews substitutes for ozone depleting
substances within a comparative risk
framework. EPA publishes lists of
acceptable and unacceptable alternatives
A determination that an alternative is
unacceptable, or acceptable only with
conditions, is made through rulemaking
Under l-IWs SNAP program,
EPA listed NMP as an acceptable
substitute for "straight organic
solvent cleaning (with terpenes,
('(•>20 petroleum hydrocarbons,
oxygenated organic solvents such
as ketones, esters, alcohols, etc.)"
Ibr metals, electronics and
precision cleaning and
"Oxygenated organic solvents
(esters, ethers, alcohols, ketones)"
for aerosol solvents (59 FR,
March 18, 1994).
Safe Drinking Water Act
(SDWA) Section 1412
(b)
1 -a cry 5 years. I-PA must publish a list of
contaminants (1) that are currently
unregulated, (2) that are known or
anticipated to occur in public water
systems, and (3) which might require
regulations under SDWA. EPA must
also determine whether to regulate at
least five contaminants from the list
every 5 years.
NMP was identified on both the
Third (2009) and Fourth (2016)
Contaminant Candidate Lists (74
FR 51850, October 8, 2009) (81
FR 81099 November 17, 2016).
Other Federal Regulations
Occupational Safety and
Health Act (OSHA)
Requires employers to provide their
workers with a place of employment free
from recognized hazards to safety and
health, such as exposure to toxic
chemicals, excessive noise levels,
mechanical dangers, heat or cold stress,
or unsanitary conditions.
OSHA has not established a PEL
for NMP.
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SlsiliiU's/Ucgiihilions
Description of Aiilhorily/Ucgiihilion
Description of Ucgiihilion
Under the Act, OSHA can issue
occupational safety and health standards
including such provisions as Permissible
Exposure Limits (PELs), exposure
monitoring, engineering and
administrative control measures and
respiratory protection.
Federal Food, Drug and
Cosmetic Act (FFDCA)
Provides the U.S Food and Drug
Administration (FDA) with authority lo
oversee the safety of food, drugs and
cosmetics.
I 'ood and Drug Administration
identifies NMP as an "Indirect
Additi\ e Used in Food Contact
Substances" specifically as:
1) an adju\ ant substance in the
preparation of sliniieides (21 CFR
176.300),
2) an adjuvant substance in the
production of polysulfone resin
authorized for use as articles
intended for use in contact with
food (21 CFR 177.1655) and
3) a residual solvent in
polyetherone sulfone resins
authorized as articles for repeated
use in contact with food (21 CFR
177.2440).
FDA also identifies NMP as a
Class 2 solvent, namely a solvent
that "should be limited in
pharmaceutical products because
of their inherent toxicity."
FDA established a Permissible
Daily Exposure (PDE) for NMP
of 5.3 mg/day with a
concentration limit of 530 ppm.
FDA's Center for Veterinary
Medicine developed a method in
2011 for detection of the residues
of NMP in edible tissues of cattle
(21 CFR 500.1410)
7493
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7494 A.2 State Laws and Regulations
7495
7496 Table Apx A-2. State Laws and Regulations
State Actions
Description of Action
State Air
Regulations
New Hampshire (Env-A 1400: Regulated Toxic Air Pollutants) lists NMP as a
regulated toxic air pollutant.
Vermont (Vermont Air Pollution Control Regulations. 52(-> 1) lists NMP as a
hazardous air contaminant.
Chemicals of
Concern to
Children
Several states have adopted reporting laws for chemicals in children's products that
include NMP including Oregon (OAR 333-016-2000), Vermont (18 V.S.A. sections
1771 to 1779) and Washington state (WAC 173-334-130) Minnesota has listed
NMP as a chemical of concern to children (Minnesota Statutes 1 1 (•> lM01 to
116.9407).
State
Permissible
Exposure Limits
California PEL is 1 ppm as an 8hr-timc-\\ciuhled a\ erage (TWA), along with a skin
notation (Cal Code Regs, title 8, section 5155)
State Right-to-
Know Acts
Massachusetts (454 CMR 21 <>(»). New Jersey (42 \ .1 R 1 709(a)) and Pennsylvania
(Chapter 323. Hazardous Substance List).
Other
In California, NMP is listed on Proposition 65 (Cal. Code Regs, title 27, section
27001) due to reproductive toxicity. California OEHHA lists a Maximum Allowable
Dose Level (M \l)l ) for inhalation exposure = 3,200 |ig/day MADL for dermal
exposure = 1 7.odd ug/day.
The California Department of Toxic Substances Control (DTSC) Safer Consumer
Products Program lists NMP as a Candidate Chemical for development toxicity and
reproductive toxicity In addition, DTSC is moving to address paint strippers
containing \'MP and specifically cautioned against replacing methylene chloride
with WIP In August 2018 California Department of Toxic Substances Control
(DTSC) Safer Consumer Products program proposed to list Paint and Varnish
Strippers and Graffiti Removers Containing NMP as a priority product citing (1)
potential for human and other organism exposure to NMP in paint and varnish
strippers and graffiti removers; and (2) the exposure has the potential to contribute to
or cause significant or widespread adverse impacts. DTSC published a Product-
mical Profile for Paint and Varnish Strippers and Graffiti Removers Containing
]•¦" ? r* to support the listing. California Department of Public Health's Hazard
Evaluation System and Information Service (HESIS) issued a Health Hazard
Advisory on NMP in 2006 and updated the Advisory in June 2014. The Advisory is
aimed at workers and employers at sites where NMP is used.
7497
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7498
7499
7500
A.3 International Laws and Regulations
Table_Apx A-3. Regulatory Actions by Other Governments and Tribes
('oiinlrv/Organi/alion Requirements and Restrictions
European Union
In 2011, NMP was listed on the Candidate list as a
Substance of Very High Concern (SVHC) under
regulation (EC) No 1907/2006 - REACH
(Registration, Evaluation, Authorization and
Restriction of Chemicals).
In March 2017, NMP was included in the public
consultation of chemicals recommended for inclusion
in Annex XIV of the European Chemicals Agency
(ECHA) under Annex (Authorisation list) of regulation
(EC) No N07/2006 - REACH (Registration.
Evaluation. Authorization and Restriction of
Chemicals)
In 2013, the Netherlands submitted a proposal under
REACH to restrict manufacturing and all industrial
and professional uses of NMP where workers'
exposure exceeds a le\ el specified in the restriction
(European Chemicals Agency (ECHA) database.
Accessed April IS, 2017).
On April IS. 2d IS. the European Union added NMP to
REACH Annex XVII, the restricted substances list.
The action specifies three conditions of restriction. The
conditions are: 1) NMP shall not be placed on the
market as a substance on its own or in mixtures in
concentrations greater than 0.3% after May 9, 2020,
unless manufacturers, importers and downstream users
have included chemical safety reports and safety data
sheets with Derived No-Effect Levels (DNELs)
relating to workers' exposures of 14,4 mg/m3 for
exposure by inhalation and 4,8 mg/kg/day for dermal
exposure; 2) NMP shall not be manufactured, or used,
as a substance on its own or in mixtures in a
concentration equal to or greater than 0.3% after May
9, 2020 unless manufacturers and downstream users
take the appropriate risk management measures and
provide the appropriate operational conditions to
ensure that exposure of workers is below the DNELs
specified above: and 3) the restrictions above shall
apply from May 9, 2024 to placing on the market for
use, or use, as a solvent or reactant in the process of
coating wires.
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('»iinlrv/()r^;Hii/:ili»n
Ucqiiimiicnls mid Ucslriclions
Australia
NMP was assessed under Human Health Tier III of the
Inventory Multi-tiered Assessment and Prioritisation
(IMAP) (National Industrial Chemicals Notification
and Assessment Scheme, NICNAS, 2017, Human
Health Tier III assessment for 2-Pyrrolidinone,
lmethyl-. Accessed April, 18 2017).
Japan
NMP is regulated in .Inpun under the following
legislation:
• Act on the 1 a aluaiion of Chemical Substances
and Regulation of their Manufacture, etc.
(Chemical Substances Control T.aw)
• Industrial Safety and Health Act
(National Institute of Technology and Evaluation
(NITE) Chemical Risk Information Platform (CHIRP).
Accessed April 18,2017).
European Union and Australia, Austria,
Belgium, Canada (Ontario), Denmark,
Finland, France, Germany, Ireland, Italy,
Latvia, New Zealand, Poland, Spain, Sweden.
Switzerland, The Netherlands, Turkey and the
United Kingdom.
Occupational exposure limits for NMP (GESTIS
International limit \ allies for chemical agents
(Occupational exposure limits, OELs) database.
Accessed April I S. 2d I 7).
7501
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7502
7503
7504
7505
7506
7507
7508
7509
7510
7511
7512
7513
7514
7515
7516
7517
7518
7519
7520
7521
7522
7523
7524
7525
7526
7527
7528
7529
7530
7531
7532
7533
7534
7535
7536
7537
7538
7539
7540
7541
7542
7543
7544
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Appendix B LIST OF SUPPLEMENTAL DOCUMENTS
1. Associated Systematic Review Data Quality Evaluation and Data Extraction Documents -
Provides additional detail and information on individual study or data evaluations and data
extractions including criteria and scoring results.
a. Risk Evaluation for N-Methylpyrrolidone (NMP), Systematic Review Supplemental File:
Data Quality Evaluation of Environmental Fate and '//'< tn sport Studies. Docket EPA-HQ-
OPPT-2019-0236 (U.S. EPA. 2.0190
b. Risk Evaluation for N-Methylpyrrolidone (NMP), Systematic Review Supplemental File:
Data Quality Evaluation of Physical Chemical Properties Studies. Docket EPA-HQ-
OPPT-2019-0236 (U.S. EPA. 2019a)
c. Risk Evaluation for N-Methylpyrrolidone tSMP), Systematic Review Supplemental File:
Data Quality Evaluation of Environmental Release and Occupational Exposure Data.
Docket EPA -HQ-OP P1-2019-0236 (US 2019k)
d. Risk Evaluation for N-Methylpyrrolidone (2-Pyrrolidinone, 1-Methyl-) Systematic Review
Supplemental File: Data Quality Evaluation <>j Environmental Release and Occupational
Exposure Data- Common Sources. Docket l'JJA-IIO-( )l'PT-2019-0236. (
20190
e. Risk Evaluation for N-Mei/iylpyrrolidone (NMP), Systematic Review Supplemental File:
Data Quality Evaluation oj Consumer and (icneral Population Exposure Studies. Docket
EPA-HQ-OPPT-2019-0236 (U.S. EF )
f. Risk Evaluation for N-Methylpyrrol idone (NMP). Systematic Review Supplemental File:
Data Quality Evaluation of Ecological Hazard Studies. Docket EPA-HQ-OPPT-2019-
0236 ( PA. 20190
g. Risk 1 .valuation for N-Methylpyrrolidone (NMP), Systematic Review Supplemental File:
Data Quality I .valuation of Human Health Hazard Studies- Animal Studies. Docket EPA-
HQ-OPPT-20 i(j-n23f> ( : ...; ; )
h. Risk I .valuation for S-\ leihylpyrrolidone (NMP), Systematic Review Supplemental File:
Data Oiiahiy Evaluation of 1 Epidemiological Studies. Docket EPA-HQ-OPPT-2019-0236
( . >:j n)
i. Risk Evaluation for \-\ leihylpyrrolidone (NMP), Systematic Review Supplemental File:
I pdates to the Data Quality Criteria for Epidemiological Studies. ( 3190
j. Risk I .valuation for N-Methylpyrrolidone (NMP), Systematic Review Supplemental File:
Daia Extraction Tables for Epidemiological Studies. Docket EPA-HQ-OPPT-2019-0236
( v °0i9s)
2. Risk Evaluation for N-Methylpyrrolidone (NMP), Supplemental Information on Occupational
Exposure Assessment. Docket EPA-HQ-OPPT-2019-0236 (U.S. EPA. 2019a) - Provides
additional details and information on the occupational exposure assessment including PBPK
modeling inputs and air concentration model equations, inputs, and outputs.
3. Risk Evaluation for N-Methylpyrrolidone (NMP), Supplemental Information on Consumer
Exposure Assessment. Docket EPA-HQ-OPPT-2019-0236 (U.S. EPA. 2019b) - Provides
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7547
7548
7549
7550
7551
7552
7553
7554
7555
7556
7557
7558
7559
7560
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additional details and information on the consumer exposure assessment, including Consumer
Exposure Model (CEM) approach, inputs and sensitivity analysis.
4. Risk Evaluation for N-Methylpyrrolidone (NMP), Benchmark Dose Modeling Supplemental File.
DocketEPA-HQ-OPPT-2019-0236 (U.S. EPA... 2019f) - Provides additional details and results
of the benchmark dose modeling of the human health hazard endpoints.
5. Risk Evaluation for N-Methylpyrrolidone (2-Pyrrolidinone, 1 Methyl-) (NMP), Supplemental
Excel File on Occupational Risk Calculations. Docket EPA-HO-OPPT-2019-0236 (l_Js
2019a)
6. Risk Evaluation for N-Methylpyrrolidone (2-Pyrrolidinone, I Methyl-) tSMP), Supplemental
Information on Consumer Exposure Assessment, Consumer Exposure Model Input Parameters.
Docket EPA-HQ-OPPT-2019-0236 (\ _ J ^n9c)
7. Risk Evaluation for N-Methylpyrrolidone (2-Pyrrolidinone. 1 Methyl-) (NMP). Supplemental
Information on Consumer Exposure Assessment, ( 'onsnmer Exposure Model Out pins. Docket
EPA-HQ-OPPT-2019-0236 OJ. S. EPA. 2019d)
8. Risk Evaluation for N-Methylpyrrolidone {2-Pyrrolnhnone. / Methyl-) (NMP), Supplemental
Information on Consumer Exposure . \sscssmem PBI'K \ lodel lupins and Outputs. Docket EPA-
HQ-OPPT-2019-0236 ( \\V\ i
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Appendix C FATE AND TRANSPORT
EPI Suite™ Model Inputs
To set up EPI Suite™ for estimating fate properties of NMP, NMP was identified using the "Name Lookup" function. The physical-
chemical properties were input based on the values in Table 1-1. EPI Suite™ was run using default settings (i.e., no other parameters
were changed or input).
WSKOW
BCFBAF
BioHCwin
ECOSAR
EPI Links
File
Edit
Functions
Batch Mode
Show
Structure
Output
Fugacity
STP
Help
EPI Suite - Welcome Screen
PhysProp
Clear Input Fields
Input CAS tt
Input Smiles:
Output
C Full
(* Summary
Input Chen. Name: N-METHYLPYRROLIDONE
Name Lookup
Henry LC:
Melting Point:
Boiling Point:
Water Depth:
Wind Velocity:
Current Velocity:
3.20E-09 atm-m /mole Water Solubility: ] 1E+00G mg/L
202 Celsius
Lake
~r
5 r
-rr
Vapor Pressure:
Log Kow:
meters
meters/sec
meters/sec
r
0.345 mm Hg
7571
7572
7573
7574
7575
7576
The Estimation Programs Interface (EPI) SuiteTM was developed by the US Environmental Protection Agency's Office of Pollution Prevention
and Toxics and Syracuse Research Corporation (SRC). It is a screening-level tool, intended for use in applications such as to quickly screen
chemicals for release potential and "bin" chemicals by priority for future work. Estimated values should not be used when experimental
(measured) values are available.
EPI SuiteTM cannot be used for all chemical substances. The intended application domain is organic chemicals. Inorganic and organometallic
chemicals generally are outside the domain.
Important information on the performance, development and application of EPI SuiteTM and the individual programs within it can be
found under the Help tab. Copyright 2000-2012 United States Environmental Protection Agency for EPI SuiteTM and all component
programs except BioHCWIN and KOAWIN.
FigureApx C-l. EPI Suite Model Inputs for Estimating NMP Fate and Transport Properties
Environmental Fate Study Summary for N-Methyl-2-pyrrolidone (NMP)
Page 360 of 487
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7577 Table Apx C-l. Biodegradation Study Summary for N-Methylpyrrolidone
Siuclj 1 \pc ijesir)
Iniliiil
( onccnlr;ilion
Inoculum
Source
(Auiiicrohic
Siiiius
Dui'iilion
Result
Com men Is
AITilhilcri
Reference
Diilii Ou;ilil>
l'.\iiliiiilion I'esiills of
l ull Siuclj Report
Water
Other; Degradation
kinetics of NMP in
liquid culture under
various parameters
>500 to <2000
mg/L
activated
sludge,
industrial,
adapted
aerobic
28h
Biodesiradaliou
Daranieler: half-
ljfe:
5u%/5.05h
The iv\ ie\\ er
agreed u illi this
study's overall
quality lc\el
(Cai et al..
2014)
High
Other; Semi-
continuous
activated sludge test
following ASTM
(1975) procedure
for biodegradation
of synthetic
detergents
100 ppm
activated
sludge,
domestic
(adaptation
not specified)
aerobic
7d
l.iodeeradation
parameter:
percent removal:
95% 7d alter 5-
day incremental
acclimation
period (primary
biodegradation:
complete
mineralization
not observed)
The review er
agreed with this
study's overall
quality level.
1 id
i i. .y 'l.i 3 )
High
Other; Static die-
away test similar to
the method
recommended by
the British Standard
Technical
Committee of
Synthetic
Detergents
100 ppm
ac1i\ aled
sludue.
domestic
(adaptation
not S] willed i
aerohic
14d
Biodesiradalion
parameter:
COD: 45%/14d:
Biodesradation
parameter:
percent removal:
95%/14d
The reviewer
agreed with this
study's overall
quality level.
(Chow and
3)
High
Other; Non-
guideline and GLP
compliant study.
1 » 1.
Acii\ aled
sludge from
(1) a
municipal
uasieualcr
treatment
plain in /.Iiii.
C/ecli
Republic and
(2) an
industrial
aerohic
4d
Biodesradation
parameter:
oxveen
consumption:
50%/4d
The reviewer
agreed with this
study's overall
quality level.
(ECHA.
2017b)
High
Page 361 of 487
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Slndj T>|>c (\c;ir)
Iniliiil
( nnccnlmlinn
Inoculum
Son
(Aniiiorohic
Sliiius
Dui'iilion
Rcsull
( nmilieu Is
Allilhilcd
Reference
l):il;i Qn;ili(\
11 \ iiliiiilion results ol°
l ull Siiid> Report
WTPin
Slovenska
Lupca,
Slovak
Republic
(pharmaceuti
cal
production)
Other; semi-
continuous system
92-200 mg/L
Activated
sludge
(adaptation
not specified)
from the
Fukashiba
Joint Waste
Water
Treatment
Plant
aerobic
24h
l.indeuradalion
Diiriiiiieier TOC:
The reviewer
agreed with this
study's overall
quality level. Also
reviewed in HERO
11)4140473.
i itsui et
at.. 1975)
High
92".,
Biodesiradalinn
Daraineler:
Dcrcenl DOC:
94%
Biodesiradalion
parameter:
percent removal:
>98%
Other; acclimated
and unacclimated
sludge, static and
continuous flow
300-1000 mg/L
accli muled
and
unaceli iiiii led
sewage
sliidue
aeinhie
18h
li> d raiilic
residence
lime in
eoiiiiiiiKMis
eel Is
Biodeeradation
parameter:
percent removal:
98%
The reviewer
agreed with this
study's overall
quality level.
Primary source
cited "Lube
Solvents No Threat
to Waste
Treatment" E.H.
Rowe and L.F.
Tullos, Jr.,
Hydrocarbon
Processing, 59, p.
63-65 (October
1980).
(BASF.
1998)
Medium
Other; not reported
1000 mg/L
aeli\ aled
sludge, non-
adapted
aerobic
Adaptation
phase of
3.5 days
for non-
Biodeeradation
parameter:
COD: >90%
The reviewer
agreed with this
study's overall
quality level.
(BASF.
1998)
Medium
Page 362 of 487
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Slndj T>|>c (\o;ir)
Iniliiil
( nnccnlmlinn
Inoculum
Son
(\n);icrnhic
Sliiius
Dui'iilion
Kosu II
( om men Is
AITiliiilod
Reference
l);il;i Qn;ili(\
11 \ iiliiiilion rcsulls ol°
l ull Slii(l> Report
acclimated
activated
sludge
Primary source
cited k Zahn and
H./. Wellens
Wasser \huasser
Forscliiinu 1 \ 1
(l'JXO)
Other; coupled-
units
Not reported
activated
sludge
(adaptation
not specified)
not specified
4-12 wks
Biodesiradation
parameter:
IX)( ': 99%
The reviewer
agreed with this
study's overall
quality level.
Primary source
cited: A
C orrelation Study
nl' I'.iodegradability
1 )elcrminations
w ilh Various
Cliemicals in
\';irious Tests" P.
(icrike and W.K.
livelier Ecotoxicity
and Environmental
Safety 3, 159
(1979).
(Ti A CIJ
' ™3.
)
Medium
Other; OECD-
screening, test not
specified
Not reported
Not rcpurial
iml s|vvilial
\ol
lepoiied
Biodesradation
parameter:
DOC: 99%
The reviewer
agreed with this
study's overall
quality level.
Primary source
cited: A
Correlation Study
of Biodegradability
Determinations
with Various
Chemicals in
Various Tests" P.
Gerike and W.K.
Fischer Ecotoxicity
and Environmental
(BASF.
1998)
Medium
Page 363 of 487
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Slndj T>|>c (\e;ir)
Iniliiil
( nnccnlmlinn
Inoculum
Son
(An (aerobic
Sliiius
Dui'iilion
Kosu II
( om men Is
AITiliiilod
Reference
l);il;i Quali(\
11 \ iiliiiilion results ol°
l ull S|ikI> Report
Safely 3, 159
(l<>79).
Other; EPA OPPTS
835.3200 (Zahn-
Wellens / EMPA
Test)
Not reported
Not reported
not specified
28d
Biodeeradalimi
Darameler:
DOC: 98%
The rc\ ie\\ er
agreed u nh this
study's overall
quality lc\ el
Primary source
cited: A
( orrelation Stud>
of 13 iodegradabil 11>
1 )eterminations
with Various
Chemicals in
\ a nous Tests" P.
(icrike and W.K.
I'ischer Ecotoxicity
and Environmental
Safety 3, 159
(1979).
(
1998)
Medium
Other; EPA OPPTS
835.3110 (Ready
Biodegradability)
Not reported
Not reported
iml specified
28d
Biodeeradalion
parameter:
DOC: 97%
The reviewer
agreed with this
study's overall
quality level.
Primary source
cited: A
Correlation Study
of Biodegradability
Determinations
with Various
Chemicals in
Various Tests" P.
Gerike and W.K.
Fischer Ecotoxicity
and Environmental
Safety 3, 159
(1979).
(BASF.
1998)
Medium
Page 364 of 487
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Sluclj T>|H' (jwir)
Iniliiil
( onccnlr;i(ion
Inoculum
Sou
(\n);icrnl)ic
Siiiius
Diii'iilion
Kosu II
( din men Is
AITiliiilod
Reference
Data Qu;ilil\
11 \ iiliiiiliou results of
l ull Siii(l> Report
Other; EPA OPPTS
835.3100 (Aerobic
Aquatic
Biodegradation)
Not reported
Not reported
not specified
Not
reported
Biodesiradalion
Da ra meter:
DOC: 95%
The reviewer
agreed with this
siud\'s overall
qualilv le\el The
source is a
summai'\
document thai
references "A
( nrrelation Stud>
of 13 iodegradabil 11>
1 ^terminations
with Various
Chemicals in
\ arious Tests" P.
(ici ike and W.K.
1 "isclicr Ecotoxicity
and 1 Environmental
Safety 3, 159
(1979).
(
1998)
Medium
OECD Guideline
301 C (Ready
Biodegradability:
Modified MITI Test
(I)); Reported as
Japanese MITI test
Not reported in
secondare
source
ac1i\ alcd
sluduc.
domestic
(adaptation
not specified)
acrohic
28d
Biodeuradalion
parameter:
BOD:
73%/28d
The reviewer
agreed with this
study's overall
quality level.
( icoloe
v and
Regulatory
Affairs.
2003)
Medium
Other;
Biodegradation of
NMP in municipal
sewage under static
and flow-through
conditions and
influence of NMP
concentrations on
non-adapted sludge
>5u in 2<><)<)<)
u 1.
acli\ aled
sludue.
adapted
acrohic
:<)(,ti
Biodeeradation
parameter:
theoretical
oxvsen uotakc:
52-93%/<206h
The reviewer
downgraded this
study's overall
quality rating.
They noted:
Analytical methods
were unclear
which limits
interpretation of
the study results.
(Gomolka
and
Gomolka.,
1981)
Medium
Soil
Page 365 of 487
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Stuclj 1 \pc (jear)
Initial
Concentration
Inoculum
Source
(Aniaerohic
Status
Duralion
Result
( 0111 men Is
AITiliated
Kcl'ercnce
Data Quality
11 \ aluation results ol°
l ull Study Report
Other; Non-
guideline laboratory
test
1.7 mg/kg
three types of
soils (clay,
loam, and
sand)
Not specified
3 months
Biodcsiradalion
Da ra meter:
elimination half-
life:
4.0 to 11.5d
Csoil);
4 u. 8.7. and
11 5d (cla>.
loam and sand)
P>kH.lcuradalkiii
The reviewer
agreed with this
study's overall
qualilv lc\cl.
("ECHA.
2017a)
Medium
raramcicr
Dcrcenl rcmo\ al
''0%/2 lcl
7578
7579
Table Apx C-2. Photolysis Study Summary for N-Methvl-2-pvrrolidonc
Study Type
(year)
\\ a\clcn«>th
kit 11 «>e
Duration
Result
Comments
AITiliiitecl
Reference
Data Quality
K\ aluation
resnIts of l ull
Study Report
Air
Other; Rate
constants for
atmospheric
reactions of 1 -
methyl-2-
pyrrolidinone
with OH radicals,
NO3 radicals, and
O3 measured and
products of the
OH radical and
NO3 radical
reactions
investigated
>300 nm
8-25 min
Photodemadation
parameter indirect
photolysis: rate
constant: for
reaction with OH
radicals:
(2.15 +/- 0.36)E-11
cm3 molecule"1 s"1;
Reaction with NO3
radicals: (1.26 +/-
0.40)E-13 cm3
molecule"1 s"1
The reviewer
agreed with this
study's overall
quality level.
(Aschmann
and
Atkinson.
1999)
High
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Sliiily Type
(year)
\Ya\elen»th
R:in»e
l)ii ration
Result
Comments
AITiliateil
Reference
Data Quality
K\ aluation
resnIts of l ull
Study Report
Other;
Photochemical
Reaction with
OH Radicals
Photodceradation
parameter: indirect
photolysis: half-life
for reaction with
OH radicals
(OSAR):
17.51 hours
The reviewer
agreed with this
study's overall
quality level.
(ECHA.
2017c)
iiigh
Water
Photocatalytic
decomposition in
aqueous solution
using light
sources of UVA,
UVC, and
UVLED
254 nm to 385
nm
120 min
Photodeeradation
parameter- indirect
photolysis w and
w/o catah si rale
conslant
0.0125 min"1 to
0.0454 min"'
Study performed
in the presence
of catalyst oral
wavelengths nm
relevant to
environmental
conditions.
(\liabadi et
ci on 12)
Unacceptable
7580
7581
IIKRO II)
Reference
3577230
Chow, S. T., Ng, T. 1. The Biodegradalion Ol' Vmelln l-2-|i\ rrolidone In \\ aler li\ Sewage Bacleria
Water Research. I9S3 17 1 17-1 IS
1583365
Aliabadi. M., Ghalireniani. 11 . l/adkhah. 1'. Sagharigar, T. Photocatalytic Degradation of N-methyl-2-
pyrrolidone In Aqueous Solutions Using l.iglil Sources of UVA, UVC and UVLED. Fresenius
Environmental Bulletin. 2012. 212120-2125
3970767
ECHA. Biodegradation in soil: ] -melliyl-2-pyrrolidone. 2017.
3970766
ECHA. Biodegradalion in water screening tests: 1-methyl-2-pyrrolidone. 2017.
3576998
Cai S, hu, Cai T, Liu S. el al 2014. Biodegradation of N-methylpyrrolidone by Paracoccus sp. NMD-4
and its degradation path\\a\ International Biodeterioration & Biodegradation 93:70-77.
http://doi.ora/10.1016/i.ibiod.2014.04.022. http://dx.doi.ora/10.1016/iibiod.2014.04.022.
1721939
Aschmann, S. M., Atkinson, R Atmospheric chemistry of 1-methyl-2-pyrrolidinone. Atmospheric
Environment. 1999. 33:591-599.
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IIKRO II)
Reference
397U781
LCI IA Phololraniformalion in air. 1 -\lclh\ l---p\ nolidonc. 2U17.
3970220
Toxicology Regulatory Affairs. 2-Pyrrolidone. 2003.
3577684
Gomolka, B., Gomolka, E THE EFFECT OF N-METHYLPYRROLID() \ 1! (WIP) ONT THE ACTION
OF ACTIVATED-SLUDGE. Acta Hydrochimica et Hydrobiologica. 198 1 ^ 555-572
4140473
BASF. (1998). N-methyl pyrrolidone biodegradability.
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Appendix D RELEASES TO THE ENVIRONMENT
Systematic Review for Environmental Exposures
During problem formulation, it was determined that the aquatic exposure pathway would not be further
analyzed for NMP. The PECO was updated accordingly and all of the "on-topic" studies that entered the
process were screened out at Level 3, prior to data evaluation. However, "on-topic" exposure literature
for NMP did follow the systematic review process. 132 references were identified as "on-topic" and
subjected to an initial title/abstract screen (Level 1) and proceeded to full-text screening (Level 2 and 3).
29 references proceeded to a "Gateway" screen (Level 3), intended to consider alignment with the
current PECO. Only 22 references that entered Level 3 moved forward to data evaluation (Level 4).
First-tier Aquatic Exposure Assessment for NMP
EPA used data from EPA's Toxics Release Inventory (TRI) to estimate NMP concentrations released to
ambient water by discharging facilities. This "first-tier" exposure assessment was used lo derive
conservative estimates of NMP surface water concentrations near facilities that reported the highest
NMP water releases. EPA identified the top 12 industries reporting the highest NMP water releases and
used the reported information to estimate surface water concentrations based on the 2015 TRI data and
EPA's Exposure and Fate Assessment Screening Tool, Version 2<) 14 The environmental release data
used for this first-tier aquatic exposure assessment and reported in the WfP Problem Formulation can
be found in Table Apx D-l ( 0 )
Table Apx D-l. Summary of NMP TRI Releases lo the Environment in 2015 (lbs)
Air Rclcsiscs
1 .siiitl Dispossi
Nil m her
ol'
l-'sicililics
Si sick Air
Rclcsiscs
l-"ii;ii(i\c
Air
Rclcsiscs
\\ silcr
Rclcsiscs
(hiss 1
1 ndcr-
liround
Injection
RCRA '
Subtitle C
landfills
AII mlicr
1.SI 11(1
Dispossil h
Oilier
Rclcsiscs
lolsil
Rclcsiscs•'
Subimal
xxv |l>
54< >.<>(.<)
T,.:r
Total
396
1,43
3,370
14.092
6,456,827
228,099
8,132,388
Data source: 2015 TRI Daia (updated October 2<>| 8) fu.s. epa. 20i7fV
a RCRA (Resource Consen alinu and Recovers \ct)
b Terminology used in these columns may noi niaich the more detailed data element names used in the TRI public data and
analysis access points.
0 These release quaniiiies do include releases due to one-time events not associated with production such as remedial
actions or earl Intakes
Surface Water Concentrations
Surface water concentrations were estimated for multiple scenarios using E-FAST 2014, which can be
used to estimate site-specific surface water concentrations based on estimated loadings of NMP into
receiving water bodies. For TRI, the facilities' reported release quantities can be based on estimates
from monitoring data or measurements (i.e., continuous, random, or periodic), mass balance
calculations, published or site-specific emission factors, or other approaches such as engineering
calculations or best engineering judgment. E-FAST 2014 incorporates stream dilution at the point of
release using stream flow distribution data contained within the model. Site-specific stream flow data
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7632
7633
7634
7635
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are applied using a National Pollutant Discharge Elimination System (NPDES) code. If a specific
discharger's NPDES code could not be identified within the E-FAST database, a surrogate site or
generic Standard Industrial Classification (SIC) code was applied.
EPA considered multiple scenarios to estimate NMP concentrations in surface water resulting from
industrial discharges. Using the 2015 TRI data and EPA's first-tier, Probabilistic Dilution Model (PDM)
within the EPA Exposure and Fate Assessment Screening Tool (E-FAST), facilities reporting the largest
releases of NMP were modeled based on the assumption of 12 or 250 days of release. The 12-day
release scenario represents an acute exposure scenario wherein periodic maintenance and cleaning
activities could result in monthly releases. The 250-day release scenario represents a chronic exposure
scenario in which standard operations may result in continuous, or more protracted discharges of NMP.
Six facilities reported direct discharges of NMP to surface waters and seven faci lilies reported transfer
of NMP to a municipal treatment facility also known as a Publicly Owned Treatment Works (POTW)
facility for treatment and discharge into surface waters.
EPA did not identify water monitoring data for NMP during its review of the national surface water
monitoring database. The 2015 TRI data on direct and indirect environmental releases were used to
estimate NMP concentrations in surface water. Direct releases represent environmental releases of NMP
that are discharged directly from a facility into a receiving water body (after treatment), whereas indirect
releases are releases from the POTW where the facility has transferred NMP. The POTW releases are
discharges to surface water that occur following treatment EPA used an estimated removal rate of 92%
in estimating NMP remaining in treated wastewater from indirect POTW discharges. Because TRI
reported facility direct releases are the amounts at discharge. EPA estimates of surface water
concentrations did not account for any additional treatment by an onsite system. The predicted surface
water concentrations presented in below in Table Apx D-2 are associated with a low flow - 7Q10,
which is an annual minimum seven-day a\ erage stream flow over a ten-year recurrence interval. No
post-release degradation or removal mechanisms (e.g., hydrolysis, aerobic degradation, photolysis,
volatilization) are applied in the calculation of the modeled surface water concentrations.
For the facility transferring NMP waste to the I'O'I'W' in Pensacola, Florida, the POTW diverts 85% of
its treated wastewater lor reuse in other industrial facilities as process water. Only 15% of the treated
wastewater is discharged into the recei\ ing water of Perdido Bay. EPA therefore, estimated the NMP
stream/recei\ ing water concentration based on 15% of total NMP-containing treated wastewater
discharged
To capture "high-end" surface water concentrations, EPA compiled the release data for six facilities that
reported the largest NMP direct water releases. This represented > 99% of the total volume of NMP
Table Apx D-2. Estimated NMP Surface Water Concentrations"
NMP
PDM:
input
PDM: stream
l op Kacilitv Discharges
Onsite NMP
Transfers
loadings
NMP
(2015)
Wastewater
to Offsite
(k«/site/dav)
concent rat ions
Releases"
POTW"
12 dav
250 dav
12 dav
250 dav
l-'acilitv Location
State
(Ihs/vr)
(Ihs/vr)
scenario
scenario
(MS/I-)
(MS/I.)
Wilmington
NC
8,987
0
339.71
16.31
224.00
10.75
Richmond
VA
4,602
0
173.96
8.35
119.70
5.75
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7658
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7663
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7666
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7669
7670
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Essex Junction
VT
451
0
17.05
0.82
44.49
2.14
Bradford
PA
26.83
0
1.01
0.05
8.49
0.4
Fort Wayne
IN
22.1
0
0.84
0.04
5.56
0.27
Wyandotte
MI
2
62.83
0.08
0.00
0.0011
0.14
Westborough
MA
100,606
183
863
Wilmington
MA
533,525
968
60
Pensacola
FL
154,798
281
878b
Saint Louis
MO
150,011
272
636
Aloha
OR
170,000
308
499
Hillsboro
OR
510,000
l->25
1,496
a From 2015 Toxics Release Inventory (TRI)
b Wastewater influent has undergone pretreatment and is treated again al this POTW
reported as a direct discharge to surface water during the 2015 TRI reporting period Since there were
many more facilities reporting indirect releases of NMP to surface water, seven of the facilities reporting
the largest indirect water releases (representing ~ 11% of the total number of facilities reporting indirect
discharges) were compiled. The volume of NMP released from these facilities encompassed more than
68% of the total volume of NMP reported as an indirect discharge lo surface water.
The "high-end" surface water concentrations (i e. those obtained assuming a low stream flow for the
receiving water body) from all PDM runs ranged lYom I 1E-03 |ig,L lo 224 |ig/L, for the acute (i.e.,
fewer than 20 days of environmental releases per \ ear) and < > 14 uu 'L lo 1,496 |ig/L chronic exposure
scenario (i.e., more than 20 days of environmental releases per \ ear assumed), respectively. The
maximum acute scenario concentration was 224 |ig/L and the maximum chronic scenario concentration
was 1,496 |ig/L. Comparing these concentrations with the respective aquatic ecological concentrations
of concern of 246 ug/L for acute and 1.70S ug/L for chronic results in no exceedances (see Table 4-1).
EPA does not anticipate a concern lo aquatic organisms from NMP discharges to surface waters.
EPA did not evaluate the human health concerns from NMP releases to surface water since drinking
water, the main source of NMP exposure from surface water, is regulated via the EPA Office of Water
Contaminant Candidate l.ist (CCL 3)
Page 371 of 487
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PEER REVIEW DRAFT, DO NOT CITE OR QUOTE
7687 Appendix E OCCUPATIONAL EXPOSURES
7688
7689
7690 Section E. 1 contains information gathered by EPA in support of understanding glove use for pure NMP
7691 and for using NMP-containing formulations.
7692 E.l Information on Gloves for Pure NMP and for Formulations
7693 containing NMP
7694 Section E. 1.1 contains information gathered by EPA in support of understanding glove use for pure
7695 NMP and for paint and coatings removal using NMP formulations Section I - . I 2 contains information
7696 on gloves and respirators from Safety Data Sheets (SDS) for NMP and N\ IP-containing Products.
7697
7698 E.l.l Specifications for Gloves for Pure NMP and in Paint and Coaling Removal
7699 Formulations containing NMP
7700 Section E. 1.1 contains information gathered by EPA in support of understanding glove use for pure
7701 NMP and for paint and coatings removal using NMP formulations ( \~HO~QPPT-2016-0231 -0200).
7702 This information may be generally useful for a broader range of uses of NMP and is presented for
7703 illustrative purposes.
7704
7705 Summary on Suitable Gloves for Pure NMP ami /// lornnilaiions
7706 For scenarios where gloves can provide protection to achie\ e benchmark MOEs, gloves should be tested
7707 to determine whether they are protective against the specific formulation of the product that contains
7708 NMP. Several studies found in the literature indicate that the best types of glove material to protect
7709 against dermal exposure to pure NMP are Silver Shield. Butyl Rubber and Ansell Barrier laminate film.
7710 The next best types of glove among those studied to use for NMP exposure would be Neoprene and
7711 Natural Rubber T.alex Among the studies, Sil\er Shield provided the best protection against NMP,
7712 whether it was in pure form or part of a tested formulation. Detailed information on these and other
7713 glove types which were e\ aluated for their permeation characteristics against NMP are provided below.
7714 The cited studies' results may he a good starting point for determining glove types to consider for glove
7715 testing.
7716 Gloves for Pure A 'MP
7717 There are many factors that determine proper chemical-resistant glove selection. In addition to the
7718 specific chemical(s) utilized, the most important factors include duration, frequency, and adversity of
7719 chemical exposure. The degree of dexterity required for the task and associated physical stress to the
7720 glove are also significant considerations. The manner in which employees are able to doff the various
7721 glove types to best prevent skin contamination is also important but sometimes overlooked.
7722 Generally, dermal exposures to the solvents in paint and coating removal formulations may be assumed
7723 to be frequent or lengthy and may result in significant exposure. These assumptions affect the proper
7724 choice of glove type and errs on the side of caution, which is advised for any personal protective
Page 372 of 487
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PEER REVIEW DRAFT, DO NOT CITE OR QUOTE
7725 equipment (PPE) decision since PPE is the last line of defense against exposure in an industrial
7726 hygienist's hierarchy of controls.
7727 TableApx E-l below summarizes commonly used industrial hygiene literature (e.g., glove selection
7728 guides, manufacturer publications, etc.) and capture the highest rated glove types from each reference.
7729 Consideration of all factors (breakthrough time, qualitative indicator (QI), and other issues raised in the
7730 comments field) allow an overall determination of effectiveness.
7731 Table Apx E-l. Glove Types Evaluated for Pure N-Methylpyrrolidone (\AfP)
Reference
(J<)\c type
Uresi kill rou «li
Time
Qu:ilil:ilne liuliciilor
('OIlllllClllS
1
Ansell Barrier
(Laminate Film)
Glove
>480 mins
Very well suited
Degradation rate. Good-
l\cellenl
Permeation rate: Excellent
Natural Rubber
75 mins
Ver\ well suited
Degradation rale Excellent.
Permeation rale Very Good
Butyl
>480 mins
Very well suited
Degradation rate: Excellent
2
Neoprene over
Natural Rubber (Best
Chem Master)
>480 mins
Safest, besl selection
Highest rating attainable
Butyl
>480 mins
Salesl. hesl selection
11 idlest rating attainable
Neoprene
(Chloroflex)
>480 mins
Safest. Ivsl selection
1 lighest rating attainable
4
Butyl
8 his
Good lor total immersion
Degradation rate: Excellent
Natural Rubber
1 > his
Good for accidental
splash protection and
intermittent contact
Degradation rate: Fair
Virile
1 45 his
Good for accidental
splash protection and
intermittent contact
Degradation rate: Fair
8
Neoprene
22b nuns
Used for high chemical
exposure
Specific glove evaluated is
Chem Ply N-440
Villi ml l.atex/
Neoprene 'N'itrile
50 mins
Used for repeated
chemical contact
Specific glove evaluated is
Trionic 0-240
10
Silver Shield (North)
Not Provided
Recommended
Silver Shield and Butyl rubber
gloves are the only two glove
types recommended by this
source
Butyl
Not Provided
Recommended
7732
7733 Based on the information from Table Apx E-l, the three best types of glove material to protect against
7734 pure NMP dermal exposure are Silver Shield, Butyl Rubber and Ansell Barrier laminate film. The next
7735 best types of glove to use for pure NMP exposure would be Neoprene and Natural Rubber/Latex. As
7736 mentioned previously, Silver Shield gloves do not provide acceptable dexterity for most workers, so
Page 373 of 487
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7737
7738
7739
7740
7741
7742
7743
7744
7745
7746
7747
7748
7749
7750
7751
7752
7753
7754
7755
7756
7757
7758
7759
7760
7761
7762
7763
7764
7765
7766
7767
7768
7769
7770
7771
7772
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7774
7775
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PEER REVIEW DRAFT, DO NOT CITE OR QUOTE
they are commonly worn as a base glove with a tighter-fitting glove (e.g. latex) over the top.
Alternatively, Butyl Rubber or Ansell Barrier laminate film gloves could be worn and would provide
significant protection.
Key Points and Examples for Paint and Coating Removal Formulations
The U.S. EPA's Safety, Health and Environmental Management Division's (SHEMD) Guideline 44
(Personal Protective Equipment) states that when working with mixtures and formulated products, the
chemical component with the shortest break-through time must be considered when determining the
appropriate glove type for protection against chemical hazards unless specific test data are available
(SHE '04). Additionally, an industrial hygienist will consider the formulation's chemical
properties, including the highest hazard component of the formulation, and whether individual
components produce synergistic degradation effects. Typically, specific test data for formulations are
not available and best judgment, based on these considerations provides the basis lor glo\ e type
selection. However, in this case there are a few publications that specifically address glo\ e types for use
with methylene chloride and NMP as part of paint and coaling remo\ al formulations.
In early 2002, an article entitled "A Comparative Analysis of (ilo\ e Permeation Resistance to Paint
Stripping Formulations" (Stull et al. 2002) specifically examined u liich glove types provide the best
protection to users of commercial paint and coaling removal products. Twenty different glove types
were evaluated for degradation and resistance to peniieation under continuous and/or intermittent
contact with seven different paint and coating remo\ al formulations in a multiple-phase experiment.
Paint and coating removal formulations included some that were methylene chloride-based and others
that were NMP-based. The study found that gloves made of Plastic Laminate (e.g. Silver Shield) resisted
permeation by the majority of paint and coating removal while Butyl Rubber provided the next best
level of permeation resistance against the majority of formulations. However, Butyl Rubber gloves did
show rapid permeation for methylene chloridc-hased formulations and would not be recommended for
methylene chloride. It should be noted that PV.\ glo\ es, shown to be effective against pure methylene
chloride, were not e\ aluated. Interestingly, more dove types resisted permeation of NMP-based
formulations than coin entional sol\ cnt-hascd products such as methylene chloride. The results showed
that relatively small-molecule, volatile, chemical-based solvents cause somewhat more degradation and
considerably more permeation of glo\ e types as compared with NMP-based formulations against the
same gloves. Key conclusions include the following: "However, paint stripper formulations represent
varying multichemical mixtures and, ultimately, commercial paint strippers must be individually
evaluated for permeation resistance against selected gloves" (Stull et al.. 2002). and, "because of several
potential synergistic effects well established in the literature and in this study for mixture permeation, it
is highly recommended that glove selection decisions be based on testing of the commercial paint
stripper against the specific glove in question" (Stull et al.. 2002).
Another study from in 2007 entitled "Protective Glove Selection for Workers using NMP-Containing
Products: Graffiti Removal" essentially came to the same conclusion; of the gloves studied Silver Shield
gloves provide the best protection against NMP-based paint and coating removal formulations (Health
and Safety Laboratory. 2007). The study states that "Butyl gloves, used with caution would be a second
choice" (Health and Safety Laboratory. 2007). The increased dexterity and robustness of Butyl gloves
were noted as an advantage of Butyl over Silver Shield. Key recommendations include that gloves
Page 374 of 487
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7778
7779
7780
7781
7782
7783
7784
7785
7786
7787
7788
7789
7790
7791
7792
7793
7794
7795
7796
7797
7798
7799
7800
7801
7802
7803
7804
7805
7806
7807
7808
7809
7810
7811
7812
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PEER REVIEW DRAFT, DO NOT CITE OR QUOTE
should be "tested against all relevant chemical formulations as a matter of routine in order to inform
glove selection" (Health and Safety Laboratory. 2007) and "assumptions of glove choice based on the
use of model compounds or similar formulations should be made with extreme caution (Health and
Safety Laboratory. 2007)." Additionally, Crook recommended that "The BS EN 374-3 continuous
contact test and its successors should remain the benchmark for chemically protective glove type
decisions" (Health and Safety Laboratory. 2007).
In summary, these studies indicate that glove permeation continuous contact testing of each
formulation is necessary to provide proper protection. These studies" results may be a good starting
point for determining glove types to consider for permeation testing. The studies found that among
gloves tested Silver Shield provide the best protection against both methylene chloride and NMP,
whether they are in pure form or as part of a tested formulation. The best allernali\ e for protection
against methylene chloride would be PVA gloves, while the best alternative for NMP protection would
be Butyl Rubber gloves. A more task-specific decision on appropriate glove type selection could be
made through employee interviews and observation of tasks using methylene chloride- or NMP-
containing products.
E.1.2 Information on Gloves and Respirators from Safely Data Sheets (SDS) for NMP
and NMP-containing Products
EPA reviewed safety data sheets (SDSs) for neat NMP and products containing NMP for information on
glove and respiratory protection. Specifically, EPA re\ iewed SDSs for each occupational exposure
scenario assessed in Section 2 4 12 EPA compiled the recommended glove materials and respiratory
protection for each occupational exposure scenario from the reviewed SDSs (total of 21 SDSs were
reviewed) in Table Apx E-2. Tor neat NMP and NMP-containing products, the SDSs recommend a
variety of glove materials, including butyl rubber (8 SDSs), nitrile rubber (9 SDSs), neoprene (8 SDSs),
natural rubber (4 SDSs), poly\ inyl chloride (PVC) (4 SDSs), latex (2 SDSs), and Teflon (1 SDS). Note
that many of the ie\ iewed SDSs included multiple glove material recommendations. Almost half of the
reviewed SDSs indicated that respiratory protection was not needed under normal conditions with
adequate ventilation, unless exposure limits are exceeded or workers experience irritation or other
symptoms (10 of 21 SDSs) Three SDSs recommend the use of respirators with organic vapor cartridges.
Four SDSs recommend the use of particulate filters in instances where mist or dusts may form while
using the NMP-containing product. Four SDSs recommend the use of a self-contained breathing
apparatus (SCB A) lor emergency situations, such as spills, that can create intensive or prolonged
exposure. Note that many of the reviewed SDSs included respiratory protection recommendations, based
on the exposure scenario (i.e., normal use, emergency, potential for mist or dust).
Page 375 of 487
-------
7814 TableApx E-2. Recommended Glove Materials and Respiratory Protection for NMP and \MP-Containing Products from Safety
7815 Datasheets
7816
Applicable Occupational Kxposure
Scenario
Material. \MI>ul.%
Recommended (Joxe M:itcri;il
Reco in in ended
Respiratory Protection
Source
Manufacturing; Repackaging; Chemical
Processing, Excluding Formulation;
Incorporation into a Formulation,
Mixture or Reaction Product;
Laboratory Use
Neat, 99-100%
Bul\ 1 I'ulilvr
No specific respirator
recommended. SDS
mdicales to use an
approved respirator if
exposure limits are
exceeded.
(Tedia.. )
Manufacturing; Repackaging; Chemical
Processing, Excluding Formulation;
Incorporation into a Formulation,
Mixture or Reaction Product;
Laboratory Use
Neat, 99%
\ilnle iiihlvi'. ivopiviv. butyl
I'll hi vr
Industrial uses: Organic
gases and vapors filter
Type A Brown
conforming to EN14387.
Laboratory Use: Half
mask, Valve filtering; or,
Half mask, plus filter
(Thermo
Fisher. 2.019)
Application of Paints, Coatings,
Adhesives and Sealants
\li\luiv. S5"d
IJutyl rubber or Teflon gloves
If vapors or mists are
generated, wear a
NIOSH/MSHA
approved organic
vapor/mist respirator or
an air supplied respirator
as appropriate. Use only
self-contained breathing
apparatus for
emergencies.
(AZEK. 2015)
Application of Paints, Coatings.
Adhesives and Sealants
Mixture. l"o
Polymer laminate; nitrile gloves
may be worn over polymer
laminate gloves to improve
dexterity
Half facepiece or full
facepiece air-purifying
respirator suitable for
organic vapors and
particulates.
(3M. 2018)
Application of Paints, Coatings,
Adhesives and Sealants
\li\Lure, <1%
Nitrile gloves
No specific respirator
recommended. SDS
indicates to use an
(Ball. 2013)
Page 376 of 487
-------
Applicable Occupntioiiiil Kxposure
Scenario
Malerial. \MI>*\1.%
Recommended (11 o\c Material
Recommended
kespi i':i(»i'v PI'oleclioil
Source
approved respirator if
exposure limits are
exceeded.
Printing and Writing
Mixture, >15%
Neoprenc. bul\ 1. or nilrile
rubber
No specific respirator
recommended. SDS
indicales to use an
approved respirator if
exposure limits are
exceeded.
(Voxel 8.
)
Printing and Writing
Mixture, 0-5%
Neoprenc. hul> 1. or nilrile
i iililvr ijlm es w nil cul'I's
No specific respirator
recommended. SDS
indicates to use an
approved respirator if
exposure limits are
exceeded.
(Novacentrix.
)
Metal Finishing a
\li\lurc. 1-5".)
Rulilvr loves
No specific respirator
recommended. SDS
indicates to use an
approved respirator if
exposure limits are
exceeded.
(U.S.
Chemical.
)
Metal Finishing a; Automom e ( ar
Servicing (aerosol use)b
\li\luiv. unspecified WIP
concenlmlion
Nilrile or polyvinyl chloride
(PVC) gloves
No specific respirator
recommended. SDS
indicates to use an
approved respirator if
exposure limits are
exceeded.
(Simoniz.
: )
Removal of Paints, Coatings. .\d liesi \es.
and Sealants
Mixture. 2<)-30%
Butyl Rubber
Half facepiece or full
facepiece air-purifying
respirator suitable for
organic vapors.
(3M. 20141
Removal of Paints, Coatings, Adhesives.
and Sealants
\li\lure. 41%
Use gloves chemically resistant
to this material (Neoprene,
Nitrile, PVC)
No specific respirator
recommended. SDS
indicates to use an
CTLS. 20161
Page 377 of 487
-------
Applicable Occupntioiiiil Kxposure
Recommended
Scenario
Malerial. \MI>*\1.%
Recommended (11 o\c Material
Respi i':i(oi'v PI'oleclioil
Source
approved respirator if
exposure limits are
exceeded.
Normal use: Use NIOSH
approved respiratory
proieel ion.
Cleaning
Mixture, 90-95%
PV( -11 ned. latex, orNitrile
glo\ es
Emergency: Self-
contained breathing
apparatus, air-line
respirator, full-face
respirator
(CresLlOU)
Normal use: not
Cleaning
Mixture, 1-5%
Viluml l.ale\ or Rubber
required.
Emergency: A2P2 -
Combo filter: gas filter
(Prestige.
2010)
type A with medium
capacity and a class P2
particle filter.
No specific respirator
recommended. SDS
Automotive Car Servicing (aerosol use)
b
\li\luie.
Neocene
indicates to use an
approved respirator if
exposure limits are
exceeded.
(Slide, 2018)
Electronics Manufacturing
Mixture. unspecified WIP
Butyl rubber
In case of low exposure,
use cartridge respirator.
In case of intensive or
(MicroChem.
concenlmlion
longer exposure, use
self-contained breathing
apparatus.
; )
Electronics Manufacturing
\li\lure. U-1%
Neoprene or natural rubber
gloves if handling an open or
leaking battery
Not necessary under
normal conditions.
(Lenmar.
2014)
Page 378 of 487
-------
Applicable Occupntioiiiil Kxposure
Recommended
Scenario
Malerial. \MI>*\1.%
Recommended (11 o\c Material
kespi i':i(oi'v PI'oleclioil
Source
When ventilation is not
sufficient to remove
lUmes from the breathing
Soldering
Mixture, 1-3%
Nitrile rublvror iKiluial rulilvr
/.one, a safety approved
respirator or self-
coniamed breathing
apparatus should be
worn
CKester. 2017)
Wear air supplied
respiratory protection if
exposure concentrations
are unknown. In case of
Fertilizer Application
Mixture, <1%
\oi|nvne glomes
inadequate ventilation or
risk of inhalation of dust,
use suitable respiratory
equipment with particle
filter.
(Koch, 2011)
Wear air supplied
respiratory protection if
exposure concentrations
are unknown. In case of
Fertilizer Application
\ll\llllV. 1 < >" .>
Chemical resistant gloves
inadequate ventilation or
risk of inhalation of mist,
use suitable respiratory
equipment with particle
filter.
(Koch, 2018)
Wood Preservatives
Mixture. l"o
Chemical-resistant gloves (such
as barrier laminate, butyl
rubber, nitrile rubber, neoprene
rubber, polyvinyl chloride,
vitro)
No specific respirator
recommended. SDS
indicates to use an
approved respirator if
exposure limits are
exceeded.
(Osmose.
)
Page 379 of 487
-------
Applicable Occupntioiiiil Kxposnre
Scenario
Malerial. \MI>*\1.%
Recommended (Jo\e Material
Recommended
Respi i':i(oi'v PI'oleclion
Source
Recycling and Disposalc
Reclaimed neat NMP, 99-
100%
chemical resislanl glows
Use NIOSH-certified,
air-purifying respirators
with organic vapor
cartridges when
concentration of vapor or
misi exceeds applicable
exposure limits.
Protection provided by
air-pu n ly 11 lg respirators
is limited.
(Safetv-Kleen.
; )
a These products are recommended for use on metal parts, but EPA does not know the eMail in w Inch these products may be used within the six
operations listed under metal finishing at 40 CFR 433.10.
b These SDSs are for aerosol cleaning products. EPA does not know llie eMail in w Inch lliese products are used in the automotive service industry.
c Saftey-Kleen is a waste management company; however, this SDS does nol explicitly state thai I lie NMP has been reclaimed.
7817
Page 380 of 487
-------
Appendix F CONSUMER EXPOSURES
F.l Overview of the E-FAST/CEM Model
The Exposure and Fate Assessment Screening Tool Version 2 (E-FAST2) Consumer Exposure
Module (CEM) was selected for the consumer exposure modeling as the most appropriate model
to use due to the lack of available emissions and monitoring data for NMP uses other than paint
removers under consideration. Moreover, EPA did not have the input parameter data from
specific NMP product chamber studies required to run more complex indoor air models for the
consumer products under the scope of this assessment. CEM uses high-end input
parameters/assumptions to generate conservative, upper-bound inhalation exposure estimates for
aerosol spray products. The advantages of CEM are the following:
1. CEM model has been peer-reviewed.
2. CEM accommodates the inputs available for the products containing NMP in the indoor air
model.
3. CEM uses the same calculation engine to compule indoor air concentrations from a source as
the Multi-Chamber Concentration and Exposure Model (MCCI AI) but does not require
measured emission values (e.g. chamber studies).
Modeling Air Concentrations and Inhalation Exposure
The model used a two-zone representation of a house lo calculate the potential acute dose rate
(mg/kg-bw/day) of NMP for users and non-users /one I represents the area where the consumer
is using the product, whereas Zone 2 represents the remainder of the house. Zone 2 can be used
for modeling passi\ e exposure lo non-users in the home (bystanders), such as children and the
elderly.
The general steps of the calculation engine within the CEM model included:
1. Introduction of the chemical (i e . WIPj into the room of use (Zone 1),
2. Transfer of the chemical to the rest of the house (Zone 2) due to exchange of air between the
different rooms,
3. Exchange of the house air with outdoor air and,
4. Summation of the exposure doses as the modeled occupant moves about the house
The chemical of concern (i.e., NMP) enters the room air through two pathways: (1) overspray of
the product and (2) e\ aporation from a thin film. Six percent (6%) of the product was assumed to
become instantly aerosolized (i.e. product overspray) and was available for inhalation.
The CEM model uses data from the evaporation of a chemical film to calculate the rate of the
mass evaporating from the application surface covered during product use (DTIC. 1981). The
model assumes air exchanges from the room of use (Zone 1) and the rest of the house (Zone 2)
according to interzonal flow. The model also allows air exchange from the house (Zone 1 & 2)
with the outdoor air.
EPA used the default activity pattern in CEM based on the occupant being present in the home
for most of the day. As the occupants moved around the house in the model, the NMP air
concentration would vary. The exposure to the calculated air concentrations were summed using
CEM to estimate a potential 24-hr dose.
Page 381 of 487
-------
The potential inhalation acute dose rates (ADR pot) are computed iteratively by calculating the
peak concentrations for each simulated 10-second interval and then summing the doses over 24
hrs. These calculations take into consideration the chemical emission rate over time, the volume
of the house and the zone of use, the air exchange rate and interzonal airflow rate, the exposed
individual's locations, body weights and inhalation rates during and after the product use. The
reader is referred to the EPA's E-FAST2 website (http://www.epa.gov/tsca-screening-tools/e-
fast-exposure-and-fate-assessment-screening-tool-version-2014) to obtain additional information
about the model, including the model documentation and algorithms used (' :¦!. EPA. 2017a).
Thus, the user's exposure to NMP depends on their activity pattern (i.e., how much time using
the product, as well as the time in the room of use or in the rest of the house) as to the
concentration of NMP in the air within each of these areas. Based on the \ ar\ ing air
concentrations estimated by the CEM model over a 24-hour period, EPA then used the PBPK
model to estimate internal dose of NMP from inhalation
Chronic exposure assessments were not performed for any of the consumer C'OL s because the
frequency of product used is unlikely to present a concern for chronic exposure.
Modeling Dermal Exposure
Since consumers do not always wear gloves when using consumer products, EPA modeled
dermal exposures for all NMP-containinu products. Though CI AI can estimate dermal exposures
using a chemical permeability coefficient. I-IW used the PBPK model to estimate the internal
dose of NMP as it is absorbed through the skin both from direct contact of the liquid product and
through absorption of vapor through skin. The PBPK model thus, estimated the total internal
dose of NMP through combined routes of exposure, inhalation, dermal and vapor through skin
and was used to estimate exposures in the Paint Remover Risk Assessment.
Page 382 of 487
-------
F.2 Supplemental Consumer Exposure and Risk Estimation
Technical Report for NMP in Paint and Coating Removal
^ PR& United States
Environmental Protection
Agency
July 2016
Office of Chemical Safety and
Pollution Prevention
Supplemental Consumer Exposure and Risk Estimation
Technical Report for NMP in Paint and Coating Removal
[RIN 2070-AK07]
July 2016
Page 383 of 487
-------
i Introduction
EPA performed this technical analysis of consumer exposure scenarios for the use of N-
methylpyrrolidone (NMP) in paint and coating removal. Consistent with its final TSCA Work
Plan Chemical Risk Assessment for NMP (EPA, 2015), this analysis adds additional exposure
scenarios associated with the use of NMP in consumer paint and coating removal.
2 Executive Summary
In 2015, EPA completed a risk assessment for NMP in paint and coating removal (EPA, 2015)7.
The NMP risk assessment found risks of concern for occupational use and certain consumer uses
of NMP in paint and coating removal. EPA conducted exposure modeling and risk analyses to
investigate additional exposure parameters to those included in the NMP risk assessment. .
The NMP risk assessment evaluated risks based on emissions data from a brush-applied product.
This supplemental analysis used the same modeling methods to evaluate exposures and estimate
risks from larger projects. This additional exposure modeling describes the same product type
(paint and coating removal product) as in the NMP risk assessment, but with extended
application times, increased product use and altered user behavior.
The expanded consumer exposure modeling used the Multi-Chamber Concentration and
Exposure Model (MCCEM) (EPA, 2010), the same model used in the NMP risk assessment.
MCCEM was used to estimate 24-hr indoor air concentrations of NMP (i.e., acute exposure) for
the additional consumer exposure modeling scenarios described here. These air concentrations
were calculated for both users8 and bystanders9 of paint and coating removal products containing
NMP in a residential setting. Generally, the modeling reported in this document adopted many of
the input parameters and assumptions described in the NMP risk assessment, with the exception
of those variations necessary to evaluate additional consumer exposure scenarios.
The risk calculations used physiologically-based pharmacokinetic (PBPK) modeling to
incorporate both the airborne exposure, calculated in this document, and the dermal exposures
resulting from product use. This is the same methodology as was applied in the NMP risk
assessment. The results of the risk calculations are discussed in the section 6 of this document.
As expected, the larger projects modeled in this analysis resulted in larger indoor air
concentrations and longer dermal exposures and based on those higher exposures, concerns for
developmental effects were found for some of the additional exposure scenarios evaluated.
7
EPA (U.S. Environmental Protection Agency). 2015. TSCA Work Plan Chemical Risk Assessment, N-Methylpyrrolidone: Paint
Stripper Use, CASRN: 872-50-4. Office of Pollution Prevention and Toxics, Washington, DC.
https://www.epa.gov/sites/production/files/2015-ll/documents/nmp_ra_3_23_15_fmal.pdf
8 Users are directly involved of the application of the painter remover to a painted surface
9 Non-users are other inhabitants of the home that spend most of their day inside but do not enter the room
where the paint remover is used.
Page 384 of 487
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3. Background of Consumer Exposure Analysis for Paint and
Coating Removal Products Presented in EPA's NMP Risk
Assessment
The assessment of consumer use of paint and coating removal products in the NMP risk
assessment used information from products containing NMP and surveys of users to estimate
concentrations of NMP in indoor air due to product use (EPA, 2015). The parameters and their
origins are explained in the NMP risk assessment, specifically in Section 2.2 and Appendix E
(EPA, 2015).
In the NMP risk assessment and in this supplemental analysis, EPA used MCCEM to estimate
NMP inhalation exposures for the consumer use scenarios (EPA, 2010). This modeling approach
was selected because emission data were available from chamber studies for a product
containing NMP. The model used a multi-zone representation of a house to calculate the NMP
exposure levels for consumers (users) and bystanders (non-users). In this model, the room in
which the product was used was represented by one or two zones, and the rest of the house
(ROH) volume represents another zone. The user was assumed to spend time in the room of use
on the day of use, whereas the non-user was modeled as spending the day in the rest of the house
or outside (EPA, 2015).
The modeling approach integrated assumptions and input parameters about the chemical
emission rate over time, the volume of the house and the room of use, the air exchange rate and
interzonal airflow rate. The model also considered the exposed individual's location during and
after product use (EPA, 2010).
MCCEM was used to calculate minute by minute air concentrations based on the behavior
patterns assumed in the model. A description of the original modeled inputs and their sources as
well as a description of how MCCEM was implemented for paint removers is also in the NMP
risk assessment (EPA, 2015).
4. Additional Exposure Analysis for Consumer Paint and Coating
Removal
Modeling using the same methodology was conducted for additional consumer exposure
scenarios to aid in understanding how exposures and risk might change by varying certain user
behaviors or product application techniques. The same consumer exposure model, MCCEM,
used for the NMP risk assessment was also used for the additional modeling described in this
document.
The parameters that were varied in the new modeling runs are (1) the size of the paint and
coating removal project, (2) the type of project undertaken (furniture, flooring and bathtub) and
(3) time lapsed prior to when the paint scrapings were removed from the house. Tables 2-5 of the
NMP risk assessment contain a list of other parameters used in the consumer exposure modeling.
Page 385 of 487
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The consumer exposure scenarios in the NMP risk assessment were based on the mass of paint
and coating removal product that was used by the 50th and 80th percentile consumers from a
survey of consumers that reported the use of a paint and coating removal product. This mass of
paint and coating removal product was used to determine the amount of painted surface area
from which paint could be removed, which was converted into a representative project. In the
NMP risk assessment, this was described as, for example a set of shelves, coffee table, bathtub,
or a chest of drawers. For this supplemental analysis, consideration was expanded to include the
potential for larger consumer projects involving paint and coating removal, such as a dining set
(table and chairs) and an entire room floor. An additional model run for the bathtub scenario was
included to evaluate exposures if the product was used twice to completely remove paint from
the surface of the tub.
Finally, the scenarios modeled in the NMP risk assessment described a consumer that removed
the scrapings to an outdoor garbage bin after the second scraping event. A model scenario, or
run, was added in this supplemental analysis to evaluate the impact of removing the scrapings
more promptly. Removing the scrapings from the room of use could reduce the mass of NMP
volatilizing in the room and consequently could reduce exposures for both the user and
bystanders.
The minute by minute outputs of these MCCEM runs were entered into a PBPK model
developed for the NMP risk assessment.
Tables 1 and 2 summarize the variants in modeling parameters for the additional exposure model
runs.
Page 386 of 487
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Table 6-1. NMP Consumer Brush- and Roller-Applied Paint Removal Scenario Descriptions and Parameters
NMP Released
Room of Use
Rest of House
User
Case
ID
Area
App
Rate,
Release
Removal Method
Volume,
Volume
ACH,
Location
During Wait
and Break
Non-User
Location
Wt. Fract.
Treated, ft2
sf/min
Fraction
m3
ACH, hr1
m3
hr1
Period
Open
1
5-min. brush application, 30-min. wait, and 10-min.
windows
A —
10
2
scrape per application; process repeated after
1.26
Coffee table
completion of first scrape. Scrapings removed from
Closed
2
house after last scrape.
Windows
0.45
Open
1
25
Chest of
drawers
12.5-min. brush application, 30-min. wait, and 25-min.
windows
B —
2
scrape per application; process repeated after
1.26
completion of first scrape. Scrapings removed from
Closed
2
house after last scrape.
Windows
0.45
1
82-min. brush application, 18-min. wait, and 125-min.
scrape per application; process repeated after 30-min.
break. Scrapings removed from house after 2ntl scrape.
54
Open
windows
1.26
438
0.45
C 2
0.5
100
Dining table
and 8 chairs
2 (Table)
1 (Chairs)
0.8695
Closed
Windows
0.45
ROH
ROH
(entire time)
3
Same as Scenario CI except scrapings removed after
each scrape.
Open
windows
1.26
1
D —
2
240
4
1-hour roller-application, 1-hour wait, 1.5-hour scrape;
process repeated after 1-hour break. Scrapings
removed from house after each scrape.
Open
windows
1.26
Floors
Closed
Windows
0.45
1
F
36
2
18-min. brush application, 30-min. wait, and 36-min.
scrape per application; process repeated with no break.
Scrapings removed from house after 2ntl scrape.
Source
Cloud 1 m3
0.18
483
0.18
2
bathtub
Same as Scenario El except entire process is repeated
after 1-hour break.
Bathroom
9 m3
Page 387 of 487
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Table 6-2. NMP Consumer Spray-Applied Paint Removal Scenario Descriptions and Parameters
NMP Released
Room of Use
Rest of House
User
Case
ID
Wt.
Fract.
Area
Treated, ft2
App
Rate,
sf/min
Release
Fraction
Removal Method "
Volume,
m3
ACH, hr1
Volume,
m3
ACH, hr
i
Location
During
Wait and
Break
Period
Non-User
Location
1
100
Dining table
41-min. spray application, 30-min. wait, and 125-min.
scrape per application; process repeated after 1-hour
break. Scrapings removed from house after 2ntl scrape.
Open
windows
1.26
F 2
and
8 chairs
4 (Table)
2 (Chairs)
Closed
Windows
0.45
3
Table (36 si)
Chairs (64 si)
Same as Scenario F1 except scrapings removed after each
scrape.
54
Open
windows
1.26
438
0.45
1
G —
2
0.5
240
4*
0.8695
1-hour spray application, 1-hour wait, 1.5-hour scrape;
process repeated after 1-hour break. Scrapings removed
from house after last scrape.
Open
windows
1.26
ROH
ROH
(entire time)
Floors
Closed
Windows
0.45
1
H
36
bathtub
4
9-min. spray application, 30-min. wait, and 36-min.
scrape per application; process repeated with no break.
Scrapings removed from house after 2nd scrape.
Source
Cloud 1 m3
0.18
483
0.18
2
Same as Scenario HI except entire process is repeated
after 1-hour break.
Bathroom
9 m3
* The application rate for spray-on floors was kept the same as for roll-on floors (Professional Judgment).
** All spray-applied cases use the "high" volatility model, which assumes the first exponential mass increases by 10-fold.
Wt. Fract. = Weight Fraction, ROH=Rest of House
Page 388 of 487
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1
2
3
4
5
6
7
8
9
10
11
12
13
14
15
16
17
18
19
20
21
22
23
24
25
26
27
28
29
30
31
32
33
5. Exposure Modeling Results
As in the NMP risk assessment, the indoor air concentrations generated by MCCEM were
combined with dermal exposures in a PBPK model. The outputs of that model are the basis for
the risk findings for the consumer use of NMP for paint and coating removal in the following
scenarios. Calculations are in a reference spreadsheet in a separate appendix titled Appendix B -
Spreadsheet: Details of NMP Exposure Model Results.
For the purpose of comparing these higher-end consumer exposures to occupational exposures
calculated in the NMP Risk Assessment, EPA also calculated indoor air concentrations using an
8-hour time weighted average (TWA) exposure (see Table D-l in Appendix D). The PBPK
model used the minute-by-minute values generated by MCCEM, not these 8-hour values.
6. Risk Estimation
Risks for acute exposures were estimated for the minute-by-minute exposure concentrations
generated by MCCEM and dermal exposures with the PBPK model. The same methodology as
was used for the NMP risk assessment with additional risk estimates assuming dermal exposure
to NMP during the time of application and scraping. The risks for developmental effects were
evaluated with a margin of exposure (MOE) approach using the health hazard value derived in
the NMP risk assessment. The hazard value is the peak blood concentration of 216 mg/L and the
benchmark MOE (the total of the uncertainty factors) is 30. The evaluation hazard values, their
origins, and application to risk estimation are explained in the NMP risk assessment, specifically
in sections 3 and 4 (EPA, 2015). The risk estimates for the exposure concentrations in this
supplemental analysis are shown in Table 4.
Risks for acute exposures for developmental effects were found for users during larger projects
in the additional scenarios evaluated. Risks were only found for non-users in the ROH in the
largest project (G2).
Table 6-3 Risk Estimates for Additional Scenarios for Users Assuming Dermal Exposure
During Application and Scrapping
Scenario
( ilo\ e I sc
MOi : for POD Cma\
21 (•> nm 1.
Ix-nchmai'k MOI- 3')
Cma\ (mu 1.)
moi:
Al. Coffee Table, Brush Application in Workshop,
Windows Open
Gloves
0.27
796
No Gloves
1.99
108
A2. Coffee Table, Brush Application in Workshop,
Windows Closed
Gloves
0.30
718
No Gloves
2.02
107
Gloves
0.65
332
Page 389 of 487
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Scenario
( ilo\ e I so
MOi : for POD Cma\
21 (•> mu 1.
Ix-nchmai'k MOI- 3')
Cma\ (mu 1.)
moi:
Bl. Chest, Brush Application in Workshop, Windows
Open
No Gloves
3.76
58
B2. Chest, Brush Application in Workshop, Windows
Closed
Gloves
0.77
282
No Gloves
3.88
55.7
CI. Dining table and chairs, Brush Application in
Workshop, Windows Open
Gloves
3.37
64.1
No Gloves
13.31
16.2
C2. Dining table and chairs, Brush Application in
Workshop, Windows Closed
Gloves
4.40
49.0
No Gloves
14.50
14.9
C3. Dining table and chairs, Brush Application in
Workshop, Windows Open, Scrapings removed after
each scrap
Gloves
2.60
83.2
No Gloves
12.44
17.4
Dl. Floors, Roller Application in Workshop, Windows
Open
Gloves
4.40
49.1
No Gloves
11.76
18.4
D2. Floors, Roller Application in Workshop, Windows
Gloves
5.58
38.7
Closed
No Gloves
13.36
16.2
El. Bathtub, Brush Application in Bathroom, Csat =
Gloves
4.17
52
1,013 mg/m3, 2 Applications
No Gloves
7.81
28
E2. Bathtub, Brush Application in Bathroom, Csat =
1,013 mg/m3, 4 Applications
Gloves
6.39
34
No Gloves
10.02
22
Fl. Dining table and chairs, Spray Application in
Workshop, Windows Open
Gloves
9.39
23
No Gloves
14.72
15
F2. Dining table and chairs, Spray Application in
Workshop, Windows Closed
Gloves
12.02
18.0
No Gloves
18.42
11.7
F3. Dining table and chairs, Spray Application in
Workshop, Windows Open
Gloves
9.27
23.3
No Gloves
14.21
15.2
Gl. Floors, Spray Application in Workshop, Windows
Gloves
23.03
9.4
Open
No Gloves
26.19
8.2
G2. Floors, Spray Application in Workshop, Windows
Gloves
30.11
7.2
Closed
No Gloves
33.61
6.4
Page 390 of 487
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38
39
40
41
42
43
44
45
46
47
48
49
50
51
52
53
54
55
56
57
58
59
60
61
62
63
64
65
66
Scenario
( ilo\ e I sc
MOi : for POD Cma\
21 (•> mu 1.
Ix-nchmai'k MOI- 3')
Cma\ (mu 1.)
moi:
HI. Bathtub, Spray Application in Bathroom, Csat =
1,013 mg/m3, 2 Applications
Gloves
22.72
9.5
No Gloves
25.32
8.5
H2. Bathtub, Spray Application in Bathroom, Csat =
1,013 mg/m3, 4 Applications
Gloves
33.64
6.4
No Gloves
38.62
5.6
7.Uncertainties and Data Limitations
The modeling of additional scenarios described here has all the same uncertainties listed in the
final NMP risk assessment document.
Furthermore, it may be unlikely that a spray-applied paint and coating removal product would be
used on projects as large as those modeled in this document. Spray-applied paint and coating
removal products may be more useful for surfaces that are curved or irregular and are difficult to
cover with a brush or roller. However, this does not prevent the potential use of spray-applied
products in the manner modeled.
8. Conclusions
As expected, the larger projects resulted in larger indoor air concentrations of NMP. New 8-hour
TWA air concentrations were calculated based on the user's pattern of moving in the home.
These updated user behavior adjusted TWA air concentrations are many times larger than those
presented in the NMP risk assessment.
The modeling results showed a small decline in exposure when scrapings from the room of use
were removed more promptly (i.e. removed after each scrape and within 4 hours rather than at
the completion of the project up to 8 hours). However, this variable is not a primary factor in the
calculated values from MCCEM.
As expected, the larger projects resulted in higher NMP peak blood concentrations. Risks were
identified for developmental effects for the larger projects.
9. References
EPA (US Environmental Protection Agency). 2010. Multi-Chamber Concentration and Exposure
Model (MCCEM) Version 1.2. https://www.epa.gov/tsca-screening-tools/forms/mccem-multi-
chamber-concentration-and-exposure-model-download-and-install (accessed on April 29, 2016).
EPA (U.S. Environmental Protection Agency). 2015. TSCA Work Plan Chemical Risk
Assessment, N-Methylpyrrolidone: Paint Stripper Use, CASRN: 872-50-4. Office of Pollution
Page 391 of 487
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67
68
69
70
71
72
73
74
75
76
77
78
79
80
81
82
83
84
85
86
87
88
89
90
91
92
93
94
95
96
97
98
99
100
101
102
103
104
105
106
107
108
109
110
111
112
113
114
115
116
117
Prevention and Toxics, Washington, DC. https://www.epa.gov/assessing-and-managing-
chemicals-under-tsca/tsca-work-plan-chemical-risk-assessment-n-0
10. Appendix A
Types of Paint Removal Modeling Scenarios:
A. Coffee table (surface area = 10 ft2; App. rate = 2 sf/min; Total duration = 90 minutes)
1. Brush-On, Workshop, User in rest of house (ROH) during wait time, ROH=0.45 Air
changes per hour (ACH), Workshop = 1.26 ACH, Interzonal air flow (IZ) = 107 m3/hr.,
0.5 Weight Fraction, Scrapings removed after 2nd scrape (WINDOWS OPEN)
2. Brush-On, Workshop, User in ROH during wait time, ROH=0.45 ACH, Workshop =
0.45 ACH (= 24.3 m3/hr.), IZ = 107 m3/hr., 0.5 Weight Fraction, Scrapings removed after
2nd scrape (WINDOWS CLOSED)
B. Chest of drawers (surface area = 25 ft2; App. rate = 2 sf/min; Total duration = 135 min)
1. Brush-On, Workshop, User in ROH during wait time, ROH=0.45 ACH, Workshop =
1.26 ACH, IZ = 107 m3/hr., 0.5 Weight Fraction, Scrapings removed after 2nd scrape
(WINDOWS OPEN)
2. Brush-On, Workshop, User in ROH during wait time, ROH=0.45 ACH, Workshop =
0.45 ACH (= 24.3 m3/hr.), IZ = 107 m3/hr., 0.5 Weight Fraction, Scrapings removed after
2nd scrape (WINDOWS CLOSED)
C. Dining table and chairs (surface area = 100 ft2 (36 ft2 for table and 64 ft2for chairs,
8 @ 8 ft2); App. rate = 2 sf/min table (18 min), 1 sf/min chairs (64 min); 18 minute wait,
Scrape rate 0.8 sf/min (125 min), 30 minute break; Total duration = 8 hours)
1. Brush-On, Workshop, User in ROH during wait time, ROH=0.45 ACH, Workshop =
1.26 ACH, IZ = 107 m3/hr., 0.5 Weight Fraction, Scrapings removed after 2nd scrape
(WINDOWS OPEN)
2. Brush-On, Workshop, User in ROH during wait time, ROH=0.45 ACH, Workshop =
0.45 ACH (= 24.3 m3/hr.), IZ = 107 m3/hr., 0.5 Weight Fraction, Scrapings removed after
2nd scrape (WINDOWS CLOSED)
3. Brush-On, Workshop, User in ROH during wait time, ROH=0.45 ACH, Workshop =
1.26 ACH, IZ = 107 m3/hr., 0.5 Weight Fraction, Scrapings removed after each scrape
(WINDOWS OPEN)
D. Floor paint removal (surface area = 240 ft2; App. rate = 4 sf/min; 1 hour wait, Scrape rate =
2.67 (1.5 hour), 1 hour break; Total duration = 8 hours)
1. Roll-On, Workshop, User in ROH during wait time, ROH=0.45 ACH, Workshop = 1.26
ACH, IZ = 107 m3/hr., 0.5 Weight Fraction, Scrapings removed after each scrape
(WINDOWS OPEN)
2. Roll-On, Workshop, User in ROH during wait time, ROH=0.45 ACH, Workshop = 0.45
ACH (= 24.3 m3/hr.), IZ = 107 m3/hr., 0.5 Weight Fraction, Scrapings removed after each
scrape (WINDOWS CLOSED)
E. Bathtub paint removal (surface area = 36 ft2; App. rate = 2 sf/min; Total duration = 2.8
hours (2 apps); 6.6 hours (4 apps))
1. Brush-On, Bathroom + Source Cloud, User in ROH during wait time, ROH=0.18 ACH,
Bathroom = 0.18 ACH, IZ (source cloud/bathroom, bathroom/ROH) = 80/35 m3/hr., 0.5
Weight Fraction (Csat =1013 mg/m3), Scrapings removed after 2nd scrape (NO
WINDOWS, 2 applications)
2. Brush-On, Bathroom + Source Cloud, User in ROH during wait time, ROH=0.18 ACH,
Bathroom =0.18 ACH, IZ (source cloud/bathroom, bathroom/ROH) = 80/35 m3/hr., 0.5
Weight Fraction (Csat = 1013 mg/m3), Scrapings removed after 2nd and 4th scrapes (NO
WINDOWS, 4 applications)
Page 392 of 487
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120
121
122
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124
125
126
127
128
129
130
131
132
133
134
135
136
137
138
139
140
141
142
143
144
145
146
147
148
149
150
151
152
153
154
F. Dining table and chairs (surface area = 100 ft2 (36 ft2 for table and 64 ft2for chairs,
8 @ 8 ft2); App. rate = 4 sf/min table (9 min), 2 sf/min chairs (32 min); 30 minute wait,
Scrape rate 0.8 sf/min (125 min), 1 hour break; Total duration = 7 hours)
1. Spray-On, Workshop, User in ROH during wait time, ROH=0.45 ACH, Workshop = 1.26
ACH, IZ = 107 m3/hr., 0.5 Weight Fraction, Scrapings removed after 2nd scrape
(WINDOWS OPEN)
2. Spray-On, Workshop, User in ROH during wait time, ROH=0.45 ACH, Workshop = 0.45
ACH (= 24.3 m3/hr.), IZ = 107 m3/hr., 0.5 Weight Fraction, Scrapings removed after 2nd
scrape (WINDOWS CLOSED)
3. Spray-On, Workshop, User in ROH during wait time, ROH=0.45 ACH, Workshop = 1.26
ACH, IZ = 107 m3/hr., 0.5 Weight Fraction, Scrapings removed after each scrape
(WINDOWS OPEN)
G. Floor paint removal (surface area = 240 ft2; App. rate = 4 sf/min; 1 hour wait, Scrape rate =
2.67 sf/min (1.5 hour), 1 hour break; Total duration = 8 hours)
1. Spray-On, Workshop, User in ROH during wait time, ROH=0.45 ACH, Workshop = 1.26
ACH, IZ = 107 m3/hr., 0.5 Weight Fraction, Scrapings removed after each scrape
(WINDOWS OPEN)
2. Spray-On, Workshop, User in ROH during wait time, ROH=0.45 ACH, Workshop = 0.45
ACH (= 24.3 m3/hr.), IZ = 107 m3/hr., 0.5 Weight Fraction, Scrapings removed after each
scrape (WINDOWS CLOSED)
H. Bathtub paint removal (surface area = 36 ft2; App. rate = 4 sf/min; Total duration = 2.5
hours (2 apps); 6 hours (4 apps))
1. Spray-On, Bathroom + Source Cloud, User in ROH during wait time, ROH=0.18 ACH,
Bathroom = 0.18 ACH, IZ (source cloud/bathroom, bathroom/ROH) = 80/35 m3/hr., 0.5
Weight Fraction (Csat =1013 mg/m3), Scrapings removed after 2nd scrape (NO
WINDOWS, 2 applications)
2. Spray -On, Bathroom + Source Cloud, User in ROH during wait time, ROH=0.18 ACH,
Bathroom =0.18 ACH, IZ (source cloud/bathroom, bathroom/ROH) = 80/35 m3/hr., 0.5
Weight Fraction (Csat =1013 mg/m3), Scrapings removed after 2nd and 4th scrapes (NO
WINDOWS, 4 applications)
Unchanged modeling parameters for all scenarios
• House volume = 492 m3
• Paint stripper consumer weight fraction = 0.5 (upper end)
• Non-user location = ROH (entire time)
Page 393 of 487
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Table A-l. Time Schedule for Brush- and Roller-Applied Paint and Coating Removal with Repeat
Application
Scenario
Elapsed Time From Time Zero, Minutes (Product User Location)
Apply 1
Wait 1
Scrape 1
Break
Apply 2
Wait 2
Scrape 2
A. Brush application to coffee table in
workshop, central tendency scenario (App
rate = 2 sf/min)
0-5
(Workshop)
5-35
(ROH)
35-45
(Workshop)
0
45-50
(Workshop)
50-80
(ROH)
80-90
(Workshop)
B. Brush application to chest in
workshop, upper-end scenario for user &
non-user
(App rate = 2 sf/min)
0-12.5
(Workshop)
12.5-42.5
(ROH)
42.5-67.5
(Workshop)
0
67.5-80
(Workshop)
80-110
(ROH)
110-135
(Workshop)
C. Brush application to dining table and
chairs in workshop, central tendency
scenario
(App rate = 2 sf/min for table; 1 sf/min
for chairs)
0-82
(Workshop)
82-100
(ROH)
100-225
(Workshop)
225-255
(ROH)
255-337
(Workshop)
337-355
(ROH)
355-480
(Workshop)
D. Roller application to floor
(App rate = 4 sf/min)
0-60
(Workshop)
60-120
(ROH)
120-210
(Workshop)
210-270
(ROH)
270-330
(Workshop)
330-390
(ROH)
390-480
(Workshop)
E. Brush application to bathtub
(App rate = 2 sf/min)
El = 2 applications
E2 = 4 apps (repeat 1st 2 apps after 1
hour break, total time = 396 min.)
0-18
(Src Cloud)
228-246
(Src Cloud)
18-48
(ROH)
246-276
(ROH)
48-84
(Src Cloud)
276-312
(Src Cloud)
0
84-102
(Src Cloud)
312-330
(Src Cloud)
102-132
(ROH)
330-360
(ROH)
132-168
(Src Cloud)
360-396
(Src Cloud)
155
Table A-2. Time Schedule for Spray-Applied Paint and Coating Removal with Repeat Application
Scenario
Elapsed Time From Time Zero, Minutes (Product User Location)
Apply 1
Wait 1
Scrape 1
Break
Apply 2
Wait 2
Scrape 2
F. Spray application to dining table and
chairs in workshop, central tendency
scenario
(App rate = 4 sf/min for table; 2 sf/min
for chairs)
0-41
(Workshop)
41-71
(ROH)
71-196
(Workshop)
196-256
(ROH)
256-297
(Workshop)
297-327
(ROH)
327-452
(Workshop)
G. Spray application to floors
(App rate = 4 sf/min)
0-60
(Workshop)
60-120
(ROH)
120-210
(Workshop)
210-270
(ROH)
270-330
(Workshop)
330-390
(ROH)
390-480
(Workshop)
H. Spray application to bathtub
(App rate = 4 sf/min)
HI = 2 applications
H2 = 4 apps (repeat 1st 2 apps after 1
hour break, total time = 360 min.)
0-9
(Src Cloud)
210-219
(Src Cloud)
9-39
(ROH)
219-249
(ROH)
39-75
(Src Cloud)
249-285
(Src Cloud)
0
75-84
(Src Cloud)
285-294
(Src Cloud)
84-114
(ROH)
294-324
(ROH)
114-150
(Src Cloud)
324-360
(Src Cloud)
156 Src Cloud = Source Cloud
157 D.5 MCCEM Inhalation Modeling Case Summaries
158
159
160
161
162 NMP Summaries
163 Formula: C5H9NO
164 CASRN: 872-50-4
Page 394 of 487
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165
166
167
168
169
170
171
172
173
174
175
176
177
178
Molecular Weight:
Density:
Appearance:
Melting Point:
Boiling Point:
Conversion units: 1 ppm =
99.13 g/mol
1.028 g/cm2 (liquid)
clear liquid
-24 °C = -11 °F = 249 K
203 °C = 397 °F = 476 K
4.054397 mg/m3
Saturation Concentration: -1,013 mg/m3 (equivalent to a vapor pressure of 0.190 Torr at
25 °C, used in Scenario 5, based on (OECD. 2007a). See Section
D.3)
Saturation Concentration: -640 mg/m3 (representing the upper end of the saturation
concentration values associated with "normal humidity
conditions." See Section D.3)
Page 395 of 487
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179
180
181
182
183
184
185
186
187
188
189
190
191
192
193
194
195
196
197
198
199
200
201
202
203
204
205
206
207
208
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210
211
212
213
214
215
NMP Scenario Al. Coffee Table, Brush-On, Workshop, User in ROH during wait time,
ROH=0.45 ACH, Workshop = 1.26 ACH (= 68 m Vhr.), IZ = 107 in Vhr., 0.5 Weight Fraction,
Scrapings removed after 2nd scrape (WINDOWS OPEN)
MCCEM Input Summary
Application Method:
Brush-on'
Volumes:
Workshop volume = 54 m3
ROH volume = 492 - 54 = 438 m3
Airflows:
W orkshop-outdoors
68 m3/h
ROH-outdoors
197.1 m3/h (0.45 ACH)
Workshop-ROH
107 m3/h
NMP Mass Released:
Coffee table = 10 sq. ft. surface area
Applied product mass = 108 g/sq. ft. = 1,080 g
Applied NMP = 1,080 g x 0.5 (wt. fraction) = 540 g
Total NMP mass released (theoretical, both exponentials) = 1,080 g x 0.5 (wt. fraction) x 0.8695
(release fraction, theoretical) = 469.53 g
Mass released per app = 234.77 g
For each of the 2 applications:
ki = 32.83/hr]
% Mass for Exponential 1 = 0.7% of Total mass applied = 0.007/0.8695 =
NMP
0.8% of released
Eoi = Mass * ki = 0.008*234.77*32.83 = 61.7 g/hr. (NOTE: only k and Mass are needed as
inputs)
k2 = 0.00237/hr.
% Mass for Exponential 2 = 86.2% of applied NMP = 0.862/0.8695 = 99.2% of released NMP
E02 = Mass * ki = 0.992*234.77*0.00237 = 0.55 g/hr. (NOTE: only k and Mass are needed as
inputs)
Application Times and Activity Patterns
Episode
Elapsed Time from Time Zero, Minutes (Product User
Location)
Apply 1
Wait 1
Scrape 1
Apply 2
Wait 2
Scrape 2
Al) Coffee Table, Brush-On,
Workshop, User ROH during wait
time, 0.45 ACH, 0.5 Weight
Fraction, WINDOWS OPEN
0-5
(Wkshp)
5-35
(ROH)
35-45
(Wkshp)
45-50
(Wkshp)
50-80
(ROH)
80-90
(Wkshp)
User in ROH at the end of Scraping 2
User in ROH for the remainder of the run (22 hours, 30 minutes)
Page 396 of 487
-------
216 Model Run Time:
217 0-24 hours
218 User takes out scrapings after 90 minutes; emissions truncated.
219
Page 397 of 487
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220
221
222
223
224
225
226
227
228
229
230
231
232
233
234
235
236
237
238
239
240
241
242
243
244
245
246
247
248
249
250
251
252
253
254
255
256
NMP Scenario A2. Coffee Table, Brush-On, Workshop, User in ROH during wait time,
ROH=0.45 ACH, Workshop = 0.45 ACH (= 24.3 inVhr.), IZ = 107 mVhr., 0.5 Weight
Fraction, Scrapings removed after 2nd scrape (WINDOWS CLOSED)
MCCEM Input Summary
Application Method:
Brush-on
Volumes:
Workshop volume = 54 m3
ROH volume = 492 - 54 = 438 m3
Airflows:
W orkshop-outdoors
24.3 m3/h
ROH-outdoors
197.1 m3/h (0.45 ACH)
Workshop-ROH
107 m3/h
NMP Mass Released:
Coffee table = 10 sq. ft. surface area
Applied product mass = 108 g/sq. ft. = 1,080 g
Applied NMP = 1,080 g x 0.5 (wt. fraction) = 540 g
Total NMP mass released (theoretical, both exponentials) = 1,080 g x 0.5 (wt. fraction) x 0.8695
(release fraction, theoretical) = 469.53 g
Mass released per app = 234.77 g
For each of the 2 applications:
ki = 32.83/hr]
% Mass for Exponential 1 = 0.7% of Total mass applied = 0.007/0.8695 =
NMP
0.8% of released
Eoi = Mass * ki = 0.008*234.77*32.83 = 61.7 g/hr. (NOTE: only k and Mass are needed as
inputs)
k2 = 0.00237/hr.
% Mass for Exponential 2 = 86.2% of applied NMP = 0.862/0.8695 = 99.2% of released NMP
E02 = Mass * ki = 0.862*234.77*0.00237 = 0.55 g/hr. (NOTE: only k and Mass are needed as
inputs)
Application Times and Activity Patterns
Episode
Elapsed Time from Time Zero, Minutes (Product User
Location)
Apply 1
Wait 1
Scrape 1
Apply 2
Wait 2
Scrape 2
A2) Coffee Table, Brush-On,
Workshop, User ROH during wait
time, 0.45 ACH, 0.5 Weight
Fraction, WINDOWS CLOSED
0-5
(Wkshp)
5-35
(ROH)
35-45
(Wkshp)
45-50
(Wkshp)
50-80
(ROH)
80-90
(Wkshp)
User in ROH at the end of Scraping 2
User in ROH for the remainder of the run (22 hours, 30 minutes)
Page 398 of 487
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257 Model Run Time:
258 0-24 hours
259 User takes out scrapings after 90 minutes; emissions truncated.
260
Page 399 of 487
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261
262
263
264
265
266
267
268
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270
271
272
273
274
275
276
277
278
279
280
281
282
283
284
285
286
287
288
289
290
291
292
293
294
295
296
297
NMP Scenario Bl. Chest, Brush-On, Workshop, User in ROH during wait time, ROH=0.45
ACH, Workshop = 1.26 ACH (= 68 mVhr.), IZ = 107 mVhr., 0.5 Weight Fraction, Scrapings
removed after 2nd scrape (WINDOWS OPEN)
MCCEM Input Summary
Application Method:
Brush-on
Volumes:
Workshop volume = 54 m3
ROH volume = 492 - 54 = 438 m3
Airflows:
W orkshop-outdoors
68 m3/h
ROH-outdoors
197.1 m3/h (0.45 ACH)
Workshop-ROH
107 m3/h
NMP Mass Released:
Chest = 25 sq. ft. surface area
Applied product mass = 2,700 g
Applied NMP = 2,700 g x 0.5 (wt. fraction) = 1,350 g
Total NMP mass released (both exponentials) = 2,700 g x 0.5 (wt. fraction) x 0.8695 (release
fraction, theoretical) =1173.8 g
Mass released per app = 586.9 g
For each of the 2 applications:
ki = 32.83/hi]
% Mass for Exponential 1 = 0.7% of Total mass applied = 0.007/0.8695 =
NMP
0.8% of released
Eoi = Mass * ki = 0.008*586.9*32.83 = 154.1 g/hr. (NOTE: only k and Mass are needed as
inputs)
k2 = 0.00237/hr
% Mass for Exponential 2 = 86.2% of applied NMP = 0.862/0.8695 = 99.2% of released NMP
E02 = Mass * ki = 0.992*586.9*0.00237 = 1.38 g/hr. (NOTE: only k and Mass are needed as
inputs)
Application Times and Activity Patterns:
Episode
Elapsed Time from Time Zero, Minutes (Product User
Location)
Apply 1
Wait 1
Scrape 1
Apply 2
Wait 2
Scrape 2
Bl) Chest, Brush-On, Workshop,
User in ROH during wait time,
0.45 ACH, 0.5 Weight Fraction,
WINDOWS OPEN
0-12.5
(Wkshp)
12.5-
42.5
(ROH)
42.5-
67.5
(Wkshp)
67.5-80
(Wkshp)
80-110
(ROH)
110-135
(Wkshp)
Jser in ROH at the end of Scraping 2
User in ROH for the remainder of the run (21 hours, 45 minutes)
Page 400 of 487
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298 Model Run Time:
299 0-24 hours
300 User takes out scrapings after 135 minutes; emissions truncated.
301
Page 401 of 487
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302
303
304
305
306
307
308
309
310
311
312
313
314
315
316
317
318
319
320
321
322
323
324
325
326
327
328
329
330
331
332
333
334
335
336
337
338
NMP Scenario B2. Chest, Brush-On, Workshop, User in ROH during wait time, ROH=0.45
ACH, Workshop = 0.45 ACH (= 24.3 inVhr.), IZ = 107 mVhr., 0.5 Weight Fraction, Scrapings
removed after 2nd scrape (WINDOWS CLOSED)
MCCEM Input Summary
Application Method:
Brush-on
Volumes:
Workshop volume = 54 m3
ROH volume = 492 - 54 = 438 m3
Airflows:
W orkshop-outdoors
24.3 m3/h
ROH-outdoors
197.1 m3/h (0.45 ACH)
Workshop-ROH
107 m3/h
NMP Mass Released:
Chest = 25 sq. ft. surface area
Applied product mass = 2,700 g
Applied NMP = 2,700 g x 0.5 (wt. fraction) = 1,350 g
Total NMP mass released (both exponentials) = 2,700 g x 0.5 (wt. fraction) x 0.8695 (release
fraction, theoretical) =1173.8 g
Mass released per app = 586.9 g
For each of the 2 applications:
ki = 32.83/hr]
% Mass for Exponential 1 = 0.7% of Total mass applied = 0.007/0.8695 =
NMP
0.8% of released
Eoi = Mass * ki = 0.008*586.9*32.83 = 154.1 g/hr. (NOTE: only k and Mass are needed as
inputs)
k2 = 0.00237/hr.
% Mass for Exponential 2 = 86.2% of applied NMP = 0.862/0.8695 = 99.2% of released NMP
E02 = Mass * ki = 0.992*586.9*0.00237 = 1.38 g/hr. (NOTE: only k and Mass are needed as
inputs)
Application Times and Activity Patterns:
Episode
Elapsed Time from Time Zero, Minutes (Product User
Location)
Apply 1
Wait 1
Scrape 1
Apply 2
Wait 2
Scrape 2
B2) Chest, Brush-On, Workshop,
User in ROH during wait time,
0.45 ACH, 0.5 Weight Fraction,
WINDOWS CLOSED
0-12.5
(Wkshp)
12.5-
42.5
(ROH)
42.5-
67.5
(Wkshp)
67.5-80
(Wkshp)
80-110
(ROH)
110-135
(Wkshp)
Jser in ROH at the end of Scraping 2
User in ROH for the remainder of the run (21 hours, 45 minutes)
Page 402 of 487
-------
339 Model Run Time:
340 0-24 hours
341 User takes out scrapings after 135 minutes; emissions truncated.
Page 403 of 487
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342
343
344
345
346
347
348
349
350
351
352
353
354
355
356
357
358
359
360
361
362
363
364
365
366
367
368
369
370
371
372
373
374
375
376
NMP Scenario CI. Dining table and chairs, Brush-On, Workshop, User in ROH during wait
time, ROH=0.45 ACH, Workshop = 1.26 ACH (= 68 inVhr.), IZ = 107 mVhr., 0.5 Weight
Fraction, Scrapings removed after 2nd scrape (WINDOWS OPEN)
MCCEM Input Summary
Application Method: Brush-on
Volumes: Workshop volume = 54 m3
ROH volume = 492 - 54 = 438 m3
Airflows:
W orkshop-outdoors
68 m3/h
ROH-outdoors
197.1 m3/h (0.45 ACH)
Workshop-ROH
107 m3/h
NMP Mass Released:
Table = 36 sq. ft. surface area; Chairs = 64 sq. ft. surface area
Applied product mass = 10,800 g
Applied NMP = 10,800 g x 0.5 (wt. fraction) = 5,400 g
Total NMP mass released (both exponentials) = 10,800 g x 0.5 (wt. fraction) x 0.8695 (release
fraction, theoretical) =4695.3 g
Mass released per app = 2347.65 g
For each of the 2 applications:
ki = 32.83/hr]
% Mass for Exponential 1 = 0.7% of Total mass applied = 0.007/0.8695 =
NMP
0.8% of released
Eoi = Mass * ki = 0.008*2347.65*32.83 = 616.6 g/hr. (NOTE: only k and Mass are needed as
inputs)
k2 = 0.00237/hr.
% Mass for Exponential 2 = 86.2% of applied NMP = 0.862/0.8695 = 99.2% of released NMP
E02 = Mass * ki = 0.992*2347.65*0.00237 = 5.52 g/hr. (NOTE: only k and Mass are needed as
inputs)
Application Times and Activity Patterns:
Episode
Elapsed Time from Time Zero,
Location
Minutes (Product User
Apply 1
Wait 1
Scrape
1
Break
Apply 2
Wait 2
Scrape
2
CI) Dining table and chairs,
Brush-On, Workshop, User in
ROH during wait time, 0.45
ACH, 0.5 Weight Fraction,
WINDOWS OPEN
0-82
(Wkshp
)
82-100
(ROH)
100-225
(Wkshp
)
225-255
(ROH)
255-337
(Wkshp
)
337-355
(ROH)
355-480
(Wkshp
)
User in ROH at the end of Scraping 2
User in ROH for the remainder of the run (16 hours)
Page 404 of 487
-------
377 Model Run Time:
378 0-24 hours
379 User takes out scrapings after 480 minutes; emissions truncated.
Page 405 of 487
-------
380
381
382
383
384
385
386
387
388
389
390
391
392
393
394
395
396
397
398
399
400
401
402
403
404
405
406
407
408
409
410
411
412
413
414
NMP Scenario C2. Dining table and chairs, Brush-On, Workshop, User in ROH during wait
time, ROH=0.45 ACH, Workshop = 0.45ACH(= 24.3 mVhr.), IZ = 107mVhr., 0.5 Weight
Fraction, Scrapings removed after 2nd scrape (WINDOWS CLOSED)
MCCEM Input Summary
Application Method:
Brush-on
Volumes:
Workshop volume = 54 m3
ROH volume = 492 - 54 = 438 m3
Airflows:
W orkshop-outdoors
24.3 m3/h
ROH-outdoors
197.1 m3/h (0.45 ACH)
Workshop-ROH
107 m3/h
NMP Mass Released:
Table = 36 sq. ft. surface area; Chairs = 64 sq. ft. surface area
Applied product mass = 10,800 g (Application rate =108 g/sf)
Applied NMP = 10,800 g x 0.5 (wt. fraction) = 5,400 g
Total NMP mass released (both exponentials) = 10,800 g x 0.5 (wt. fraction) x 0.8695 (release
fraction, theoretical) =4695.3 g
Mass released per app = 2347.65 g
For each of the 2 applications:
ki = 32.83/hr]
% Mass for Exponential 1 = 0.7% of Total mass applied = 0.007/0.8695 =
NMP
0.8% of released
Eoi = Mass * ki = 0.008*2347.65*32.83 = 616.6 g/hr. (NOTE: only k and Mass are needed as
inputs)
k2 = 0.00237/hr.
% Mass for Exponential 2 = 86.2% of applied NMP = 0.862/0.8695 = 99.2% of released NMP
E02 = Mass * ki = 0.992*2347.65*0.00237 = 5.52 g/hr. (NOTE: only k and Mass are needed as
inputs)
Application Times and Activity Patterns:
Episode
Elapsed Time from Time Zero,
Location
Minutes (Product User
Apply 1
Wait 1
Scrape
1
Break
Apply 2
Wait 2
Scrape
2
C2) Dining table and chairs,
Brush-On, Workshop, User in
ROH during wait time, 0.45
ACH, 0.5 Weight Fraction,
WINDOWS CLOSED
0-82
(Wkshp
)
82-100
(ROH)
100-225
(Wkshp
)
225-255
(ROH)
255-337
(Wkshp
)
337-355
(ROH)
355-480
(Wkshp
)
User in ROH at the end of Scraping 2
Page 406 of 487
-------
415 User in ROH for the remainder of the run (16 hours)
416
417 Model Run Time:
418 0-24 hours
419 User takes out scrapings after 480 minutes; emissions truncated.
Page 407 of 487
-------
420
421
422
423
424
425
426
427
428
429
430
431
432
433
434
435
436
437
438
439
440
441
442
443
444
445
446
447
448
449
450
451
452
453
454
NMP Scenario C3. Dining table and chairs, Brush-On, Workshop, User in ROH during wait
time, ROH=0.45 ACH, Workshop = 1.26 ACH (= 68 inVhr.), IZ = 107 mVhr., 0.5 Weight
Fraction, Scrapings removed after each scrape (WINDOWS OPEN)
MCCEM Input Summary
Application Method:
Brush-on
Volumes:
Workshop volume = 54 m3
ROH volume = 492 - 54 = 438 m3
Airflows:
W orkshop-outdoors
68 m3/h
ROH-outdoors
197.1 m3/h (0.45 ACH)
Workshop-ROH
107 m3/h
NMP Mass Released:
Table = 36 sq. ft. surface area; Chairs = 64 sq. ft. surface area
Applied product mass = 10,800 g (Application rate =108 g/sf)
Applied NMP = 10,800 g x 0.5 (wt. fraction) = 5,400 g
Total NMP mass released (both exponentials) = 10,800 g x 0.5 (wt. fraction) x 0.8695 (release
fraction, theoretical) =4695.3 g
Mass released per app = 2347.65 g
For each of the 2 applications:
ki = 32.83/hr]
% Mass for Exponential 1 = 0.7% of Total mass applied = 0.007/0.8695 =
NMP
0.8% of released
Eoi = Mass * ki = 0.008*2347.65*32.83 = 616.6 g/hr. (NOTE: only k and Mass are needed as
inputs)
k2 = 0.00237/hr.
% Mass for Exponential 2 = 86.2% of applied NMP = 0.862/0.8695 = 99.2% of released NMP
E02 = Mass * ki = 0.992*2347.65*0.00237 = 5.52 g/hr. (NOTE: only k and Mass are needed as
inputs)
Application Times and Activity Patterns:
Episode
Elapsed Time from Time Zero,
Location
Minutes (Product User
Apply 1
Wait 1
Scrape
1
Break
Apply 2
Wait 2
Scrape
2
C3) Dining table and chairs,
Brush-On, Workshop, User in
ROH during wait time, 0.45
ACH, 0.5 Weight Fraction,
WINDOWS OPEN
0-82
(Wkshp
)
82-100
(ROH)
100-225
(Wkshp
)
225-255
(ROH)
255-337
(Wkshp
)
337-355
(ROH)
355-480
(Wkshp
)
User in ROH at the end of Scraping 2
Page 408 of 487
-------
455 User in ROH for the remainder of the run (16 hours)
456
457 Model Run Time:
458 0-24 hours
459 User takes out scrapings after 225 and 480 minutes; emissions truncated.
Page 409 of 487
-------
460
461
462
463
464
465
466
467
468
469
470
471
472
473
474
475
476
477
478
479
480
481
482
483
484
485
486
487
488
489
490
491
492
493
494
495
NMP Scenario Dl. Floor, Brush-On, Workshop, User in ROH during wait time, ROH=0.45
ACH, Workshop = 1.26 ACH (= 68 mVhr.), IZ = 107 mVhr., 0.5 Weight Fraction, Scrapings
removed after each scrape (WINDOWS OPEN)
MCCEM Input Summary
Application Method:
Brush-on
Volumes:
Workshop volume = 54 m3
ROH volume = 492 - 54 = 438 m3
Airflows:
W orkshop-outdoors
68 m3/h
ROH-outdoors
197.1 m3/h (0.45 ACH)
Workshop-ROH
107 m3/h
NMP Mass Released:
Floor = 240 sq. ft. surface area
Applied product mass = 25,920 g (Application rate = 108 g/sf)
Applied NMP = 25,920 g x 0.5 (wt. fraction) = 12,960 g
Total NMP mass released (both exponentials) = 25,920 g x 0.5 (wt. fraction) x 0.8695 (release
fraction, theoretical) =11,268.7 g
Mass released per app = 5634.4 g
For each of the 2 applications:
ki = 32.83/hr]
% Mass for Exponential 1 = 0.7% of Total mass applied = 0.007/0.8695 =
NMP
0.8% of released
Eoi = Mass * ki = 0.008*5634.4*32.83 = 1479.8 g/hr. (NOTE: only k and Mass are needed as
inputs)
k2 = 0.00237/hr.
% Mass for Exponential 2 = 86.2% of applied NMP = 0.862/0.8695 = 99.2% of released NMP
E02 = Mass * ki = 0.992*5634.4*0.00237 = 13.25 g/hr. (NOTE: only k and Mass are needed as
inputs)
Application Times and Activity Patterns:
Episode
Elapsed Time from Time Zero,
Location
Minutes (Product User
Apply 1
Wait 1
Scrape
1
Break
Apply 2
Wait 2
Scrape
2
Dl) Floor, Roll-on, Workshop,
User in ROH during wait time,
0.45 ACH, 0.5 Weight Fraction,
WINDOWS OPEN
0-60
(Wkshp
)
60-120
(ROH)
120-210
(Wkshp
)
210-270
(ROH)
270-330
(Wkshp
)
330-390
(ROH)
390-480
(Wkshp
)
User in ROH at the end of Scraping 2
User in ROH for the remainder of the run (16 hours)
Page 410 of 487
-------
496
497 Model Run Time:
498 0-24 hours
499 User takes out scrapings after 210 and 480 minutes; emissions truncated.
Page 411 of 487
-------
500
501
502
503
504
505
506
507
508
509
510
511
512
513
514
515
516
517
518
519
520
521
522
523
524
525
526
527
528
529
530
531
532
533
534
535
NMP Scenario D2. Floor, Brush-On, Workshop, User in ROH during wait time, ROH=0.45
ACH, Workshop = 0.45 ACH (= 24.3 inVhr.), IZ = 107 mVhr., 0.5 Weight Fraction, Scrapings
removed after each scrape (WINDOWS CLOSED)
MCCEM Input Summary
Application Method:
Brush-on
Volumes:
Workshop volume = 54 m3
ROH volume = 492 - 54 = 438 m3
Airflows:
W orkshop-outdoors
24.3 m3/h
ROH-outdoors
197.1 m3/h (0.45 ACH)
Workshop-ROH
107 m3/h
NMP Mass Released:
Floor = 240 sq. ft. surface area
Applied product mass = 25,920 g (Application rate = 108 g/sf)
Applied NMP = 25,920 g x 0.5 (wt. fraction) = 12,960 g
Total NMP mass released (both exponentials) = 25,920 g x 0.5 (wt. fraction) x 0.8695 (release
fraction, theoretical) =11,268.7 g
Mass released per app = 5634.4 g
For each of the 2 applications:
ki = 32.83/hr]
% Mass for Exponential 1 = 0.7% of Total mass applied = 0.007/0.8695 =
NMP
0.8% of released
Eoi = Mass * ki = 0.008*5634.4*32.83 = 1479.8 g/hr. (NOTE: only k and Mass are needed as
inputs)
k2 = 0.00237/hr.
% Mass for Exponential 2 = 86.2% of applied NMP = 0.862/0.8695 = 99.2% of released NMP
E02 = Mass * ki = 0.992*5634.4*0.00237 = 13.25 g/hr. (NOTE: only k and Mass are needed as
inputs)
Application Times and Activity Patterns:
Episode
Elapsed Time from Time Zero,
Location
Minutes (Product User
Apply 1
Wait 1
Scrape
1
Break
Apply 2
Wait 2
Scrape
2
D2) Floor, Roll-on, Workshop,
User in ROH during wait time,
0.45 ACH, 0.5 Weight Fraction,
WINDOWS CLOSED
0-60
(Wkshp
)
60-120
(ROH)
120-210
(Wkshp
)
210-270
(ROH)
270-330
(Wkshp
)
330-390
(ROH)
390-480
(Wkshp
)
User in ROH at the end of Scraping 2
User in ROH for the remainder of the run (16 hours)
Page 412 of 487
-------
536
537 Model Run Time:
538 0-24 hours
539 User takes out scrapings after 210 and 480 minutes; emissions truncated
Page 413 of 487
-------
540
541
542
543
544
545
546
547
548
549
550
551
552
553
554
555
556
557
558
559
560
561
562
563
564
565
566
567
568
569
570
571
572
573
574
NMP Scenario El. Bathroom, Brush-On, Bathroom + Source Cloud, User in ROH during
wait time, R()H=0.18 A CI I, Bathroom = 0.18 ACH, IZ (source cloud/bathroom,
bathroom/ROH) = 80, 35 m3/hr., 0.5 Weight Fraction (Csat = 1013 mg/m3), Scrapings
removed after 2nd scrape (WINDOWS CLOSED, 2 applications)
MCCEM Input Summary
MCCEM saturation concentration constraint invoked at 1013 mg/m3
Application Method: Brush-on
Volumes:
Bathroom Volume = 9 m3 (8 m3 after subtracting source cloud zone)
Source Cloud Volume = 1 m3
ROH volume = 492 - 9 = 483 m3
Airflows:
Bathroom-outdoors
1.6 m3/h
Source cloud - bathroom
80 m3/h
Source cloud - outdoors
0
ROH-outdoors
86.9 m3/h (0.18 ACH)
Bathroom-ROH
35 m3/h
NMP Mass Released:
Bathtub = 36 sq. ft. surface area
Applied product mass = 3,888 g (Application rate = 108 g/sf)
Applied NMP = 3,888 g x 0.5 (wt. fraction) = 1,944 g
Total NMP mass released (both exponentials) = 3,888 g x 0.5 (wt. fraction) x 0.8695 (release
fraction, theoretical) = 1690.3 g
Mass released per app = 845.15 g
For each of the 2 applications:
ki = 32.83/hr]
% Mass for Exponential 1 = 0.7% of Total mass applied = 0.007/0.8695 =
InmpI
0.8% of released
Eoi = Mass * ki = 0.008*845.15.4*32.83 = 222.0 g/hr. (NOTE: only k and Mass are needed as
inputs)
k2 = 0.00237/hr.
% Mass for Exponential 2 = 86.2% of applied NMP = 0.862/0.8695 = 99.2% of released NMP
E02 = Mass * k2 = 0.992*845.15*0.00237 = 1.99 g/hr. (NOTE: only k and Mass are needed as
inputs)
Page 414 of 487
-------
575 Application Times and Activity Patterns:
Episode
Elapsed Time from Time Zero, Minutes (Product User
Location)
Apply 1
Wait 1
Scrape 1
Apply 2
Wait 2
Scrape 2
El) Bathtub, Brush-On,
Bathroom + Source Cloud, User
in ROH during wait time, 0.18
ACH, 0.5 Wt. Fract.
0-18
(SrcClou
d)
18-48
(ROH)
48-84
(SrcClou
d)
84-102
(SrcClou
d)
102-132
(ROH)
132-168
(SrcClou
d)
576 User in ROH at the end of Scraping 2
577 User in ROH for the remainder of the run (21 hours, 12 minutes)
578
579 Model Run Time:
580 0-24 hours
581 User takes out scrapings after 168 minutes; emissions truncated.
582
Page 415 of 487
-------
583
584
585
586
587
588
589
590
591
592
593
594
595
596
597
598
599
600
601
602
603
604
605
606
607
608
609
610
611
612
613
614
615
616
617
NMP Scenario E2. Bathroom, Brush-On, Bathroom + Source Cloud, User in ROH during
wait time, R()H=0.18 A CI I, Bathroom = 0.18 ACH, IZ (source cloud/bathroom,
bathroom/ROH) = 80, 35 m3/hr., 0.5 Weight Fraction (Csat = 1013 mg/m3), Scrapings
removed after 2nd and 4th scrapes (WINDOWS CLOSED, 4 applications)
MCCEM Input Summary
MCCEM saturation concentration constraint invoked at 1013 mg/m3
Application Method: Brush-on
Volumes:
Bathroom Volume = 9 m3 (8 m3 after subtracting source cloud zone)
Source Cloud Volume = 1 m3
ROH volume = 492 - 9 = 483 m3
Airflows:
Bathroom-outdoors
1.6 m3/h
Source cloud - bathroom
80 m3/h
Source cloud - outdoors
0
ROH-outdoors
86.9 m3/h (0.18 ACH)
Bathroom-ROH
35 m3/h
NMP Mass Released:
Bathtub = 36 sq. ft. surface area
Applied product mass = 3,888 g (Application rate = 108 g/sf)
Applied NMP = 3,888 g x 0.5 (wt. fraction) = 1,944 g
Total NMP mass released (both exponentials) = 3,888 g x 0.5 (wt. fraction) x 0.8695 (release
fraction, theoretical) = 1690.3 g
Mass released per app = 845.15 g
For each of the 2 applications:
ki = 32.83/hr]
% Mass for Exponential 1 = 0.7% of Total mass applied = 0.007/0.8695 =
InmpI
0.8% of released
Eoi = Mass * ki = 0.008*845.15.4*32.83 = 222.0 g/hr. (NOTE: only k and Mass are needed as
inputs)
k2 = 0.00237/hr.
% Mass for Exponential 2 = 86.2% of applied NMP = 0.862/0.8695 = 99.2% of released NMP
E02 = Mass * k2 = 0.992*845.15*0.00237 = 1.99 g/hr. (NOTE: only k and Mass are needed as
inputs)
Page 416 of 487
-------
618 Application Times and Activity Patterns:
Episode
Elapsed Time from Time Zero, Minutes (Product User
Location)
Apply
1&3
Wait
1&3
Scrape
1&3
Apply
2 &4
Wait
2&4
Scrape
2&4
E2) Bathtub, Brush-On, Bathroom + Source Cloud, User in
ROH during wait time, 0.18 ACH, 0.5 Weight Fraction
1st and 2nd Application
0-18
(SrcClou
d)
18-48
(ROH)
48-84
(SrcClou
d)
84-102
(SrcClou
d)
102-132
(ROH)
132-168
(SrcClou
d)
3rd and 4th Application
228-246
(SrcClou
d)
246-276
(ROH)
276-312
(SrcClou
d)
312-330
(SrcClou
d)
330-360
(ROH)
360-396
(SrcClou
d)
619 User in ROH at the end of Scraping 2 and 4
620 User in ROH for the remainder of the run (17 hours, 24 minutes)
621
622 Model Run Time:
623 0-24 hours
624 User takes out scrapings after 168 and 396 minutes; emissions truncated.
625
Page 417 of 487
-------
626
627
628
629
630
631
632
633
634
635
636
637
638
639
640
641
642
643
644
645
646
647
648
649
650
651
652
653
654
655
656
657
658
659
660
NMP Scenario Fl. Dining table and chairs, Spray-On, Workshop, User in ROH during wait
time, ROH=0.45 ACH, Workshop = 1.26 ACH (= 68 inVhr.), IZ = 107 mVhr., 0.5 Weight
Fraction, Scrapings removed after 2nd scrape (WINDOWS OPEN)
MCCEM Input Summary
Application Method: Spray-on
Volumes: Workshop volume = 54 m3
ROH volume = 492 - 54 = 438 m3
Airflows:
W orkshop-outdoors
68 m3/h
ROH-outdoors
197.1 m3/h (0.45 ACH)
Workshop-ROH
107 m3/h
NMP Mass Released:
Table = 36 sq. ft. surface area; Chairs = 64 sq. ft. surface area
Applied product mass = 8,100 g (Application rate = 81 g/sf)
Overspray = 0.05*8,100 g = 405 g
Total Product Mass = 8,100 + 405 = 8,505 g
Total NMP Mass = 8,505 g x 0.5 (wt. fraction) = 4,252.5 g
Total NMP mass released (both exponentials) = 4,252.5 x 0.8695 (release fraction, theoretical) =
3697.5 g
Mass released per app = 1848.8 g
For each of the 2 applications:
ki = 32.83/hr.
% Mass for Exponential 1 = 7.0% of Total mass applied = 0.07/0.8695 = |8% of released NMP
Eoi = Mass * ki = 0.08*1848.8*32.83 = 4855.7 g/hr. (NOTE: only k and Mass are needed as
inputs)
k2 = 0.00237/hr.
% Mass for Exponential 2 = 79.95% of applied NMP = 0.7995/0.8695 = 91.9% of released
NMP
E02 = Mass * k2 = 0.919*1848.8*0.00237 = 4.03 g/hr. (NOTE: only k and Mass are needed as
inputs)
Application Times and Activity Patterns:
Episode
Elapsed Time from Time Zero,
Location
Minutes (Product User
Apply 1
Wait 1
Scrape
1
Break
Apply 2
Wait 2
Scrape
2
Fl) Dining table and chairs,
Spray-On, Workshop, User in
ROH during wait time, 0.45
ACH, 0.5 Weight Fraction,
WINDOWS OPEN
0-41
(Wkshp
)
41-71
(ROH)
71-196
(Wkshp
)
196-256
(ROH)
256-297
(Wkshp
)
297-327
ROH)
327-452
(Wkshp
)
User in ROH at the end of Scraping 2
User in ROH for the remainder of the run (16 hours, 28 minutes)
Page 418 of 487
-------
661
662 Model Run Time:
663 0-24 hours
664 User takes out scrapings after 452 minutes; emissions truncated.
Page 419 of 487
-------
665
666
667
668
669
670
671
672
673
674
675
676
677
678
679
680
681
682
683
684
685
686
687
688
689
690
691
692
693
694
695
696
697
698
699
NMP Scenario F2. Dining table and chairs, Spray-On, Workshop, User in ROH during wait
time, ROH=0.45 ACH, Workshop = 0.45ACH(= 24.3 mVhr.), IZ = 107mVhr., 0.5 Weight
Fraction, Scrapings removed after 2nd scrape (WINDOWS CLOSED)
MCCEM Input Summary
Application Method: Spray-on
Volumes: Workshop volume = 54 m3
ROH volume = 492 - 54 = 438 m3
Airflows:
W orkshop-outdoors
24.3 m3/h
ROH-outdoors
197.1 m3/h (0.45 ACH)
Workshop-ROH
107 m3/h
NMP Mass Released:
Table = 36 sq. ft. surface area; Chairs = 64 sq. ft. surface area
Applied product mass = 8,100 g (Application rate = 81 g/sf)
Overspray = 0.05*8,100 g = 405 g
Total Product Mass = 8,100 + 405 = 8,505 g
Total NMP Mass = 8,505 g x 0.5 (wt. fraction) = 4,252.5 g
Total NMP mass released (both exponentials) = 4,252.5 x 0.8695 (release fraction, theoretical) =
3697.5 g
Mass released per app = 1848.8 g
For each of the 2 applications:
ki = 32.83/hr.
% Mass for Exponential 1 = 7.0% of Total mass applied = 0.07/0.8695 = |8% of released NMP
Eoi = Mass * ki = 0.08*1848.8*32.83 = 4855.7 g/hr. (NOTE: only k and Mass are needed as
inputs)
k2 = 0.00237/hr.
% Mass for Exponential 2 = 79.95% of applied NMP = 0.7995/0.8695 = 91.9% of released
NMP
E02 = Mass * k2 = 0.919*1848.8*0.00237 = 4.03 g/hr. (NOTE: only k and Mass are needed as
inputs)
Application Times and Activity Patterns:
Episode
Elapsed Time from Time Zero,
Location
Minutes (Product User
Apply 1
Wait 1
Scrape
1
Break
Apply 2
Wait 2
Scrape
2
F2) Dining table and chairs,
Spray-On, Workshop, User in
ROH during wait time, 0.45
ACH, 0.5 Weight Fraction,
WINDOWS CLOSED
0-41
(Wkshp
)
41-71
(ROH)
71-196
(Wkshp
)
196-256
(ROH)
256-297
(Wkshp
)
297-327
ROH)
327-452
(Wkshp
)
User in ROH at the end of Scraping 2
User in ROH for the remainder of the run (16 hours, 28 minutes)
Page 420 of 487
-------
700
701 Model Run Time:
702 0-24 hours
703 User takes out scrapings after 452 minutes; emissions truncated.
Page 421 of 487
-------
704
705
706
707
708
709
710
711
712
713
714
715
716
717
718
719
720
721
722
723
724
725
726
727
728
729
730
731
732
733
734
735
736
737
738
NMP Scenario F3. Dining table and chairs, Spray-On, Workshop, User in ROH during wait
time, ROH=0.45 ACH, Workshop = 1.26 ACH (= 68 inVhr.), IZ = 107 mVhr., 0.5 Weight
Fraction, Scrapings removed after each scrape (WINDOWS OPEN)
MCCEM Input Summary
Application Method: Spray-on
Volumes: Workshop volume = 54 m3
ROH volume = 492 - 54 = 438 m3
Airflows:
W orkshop-outdoors
68 m3/h
ROH-outdoors
197.1 m3/h (0.45 ACH)
Workshop-ROH
107 m3/h
NMP Mass Released:
Table = 36 sq. ft. surface area; Chairs = 64 sq. ft. surface area
Applied product mass = 8,100 g (Application rate = 81 g/sf)
Overspray = 0.05*8,100 g = 405 g
Total Product Mass = 8,100 + 405 = 8,505 g
Total NMP Mass = 8,505 g x 0.5 (wt. fraction) = 4,252.5 g
Total NMP mass released (both exponentials) = 4,252.5 x 0.8695 (release fraction, theoretical) =
3697.5 g
Mass released per app = 1848.8 g
For each of the 2 applications:
ki = 32.83/hr.
% Mass for Exponential 1 = 7.0% of Total mass applied = 0.07/0.8695 = |8% of released NMP
Eoi = Mass * ki = 0.08*1848.8*32.83 = 4855.7 g/hr. (NOTE: only k and Mass are needed as
inputs)
k2 = 0.00237/hr.
% Mass for Exponential 2 = 79.95% of applied NMP = 0.7995/0.8695 = 91.9% of released
NMP
E02 = Mass * k2 = 0.919*1848.8*0.00237 = 4.03 g/hr. (NOTE: only k and Mass are needed as
inputs)
Application Times and Activity Patterns:
Episode
Elapsed Time from Time Zero,
Location
Minutes (Product User
Apply 1
Wait 1
Scrape
1
Break
Apply 2
Wait 2
Scrape
2
F3) Dining table and chairs,
Spray-On, Workshop, User in
ROH during wait time, 0.45
ACH, 0.5 Weight Fraction,
WINDOWS OPEN
0-41
(Wkshp
)
41-71
(ROH)
71-196
(Wkshp
)
196-256
(ROH)
256-297
(Wkshp
)
297-327
ROH)
327-452
(Wkshp
)
User in ROH at the end of Scraping 2
User in ROH for the remainder of the run (16 hours, 28 minutes)
Page 422 of 487
-------
739
740 Model Run Time:
741 0-24 hours
742 User takes out scrapings after 196 and 452 minutes; emissions truncated.
Page 423 of 487
-------
743
744
745
746
747
748
749
750
751
752
753
754
755
756
757
758
759
760
761
762
763
764
765
766
767
768
769
770
771
772
773
774
775
776
777
778
NMPScenario Gl. Floor, Spray-On, Workshop, User in ROHduring wait time, ROH=0.45
ACH, Workshop = 1.26 ACH (= 68 mVhr.), IZ = 107 mVhr., 0.5 Weight Fraction, Scrapings
removed after each scrape (WINDOWS OPEN)
MCCEM Input Summary
Application Method: Spray-on
Volumes: Workshop volume = 54 m3
ROH volume = 492 - 54 = 438 m3
Airflows:
W orkshop-outdoors
68 m3/h
ROH-outdoors
197.1 m3/h (0.45 ACH)
Workshop-ROH
107 m3/h
NMP Mass Released:
Floor = 240 sq. ft. surface area
Applied product mass = 19,440 g (Application rate = 81 g/sf)
Overspray = 0.05*19,440 g = 972 g
Total Product Mass = 19,440 + 972 = 20,412 g
Total NMP Mass = 20,412 g x 0.5 (wt. fraction) = 10,206 g
Total NMP mass released (both exponentials) = 10,206 x 0.8695 (release fraction, theoretical) =
8,874.1 g
Mass released per app = 4437.1 g
For each of the 2 applications:
ki = 32.83/hr.
% Mass for Exponential 1 = 7.0% of Total mass applied = 0.07/0.8695 = |8% of released NMP
Eoi = Mass * ki = 0.08*4437.1*32.83 = 11,653.6 g/hr. (NOTE: only k and Mass are needed as
inputs)
k2 = 0.00237/hr.
% Mass for Exponential 2 = 79.95% of applied NMP = 0.7995/0.8695 = 91.9% of released
NMP
E02 = Mass * k2 = 0.919*4437.1*0.00237 = 9.66 g/hr. (NOTE: only k and Mass are needed as
inputs)
Application Times and Activity Patterns:
Episode
Elapsed Time from Time Zero,
Location
Minutes (Product User
Apply 1
Wait 1
Scrape
1
Break
Apply 2
Wait 2
Scrape
2
Gl) Floor, Spray-on, Workshop,
User in ROH during wait time,
0.45 ACH, 0.5 Weight Fraction,
WINDOWS OPEN
0-60
(Wkshp
)
60-120
(ROH)
120-210
(Wkshp
)
210-270
(ROH)
270-330
(Wkshp
)
330-390
(ROH)
390-480
(Wkshp
)
User in ROH at the end of Scraping 2
User in ROH for the remainder of the run (16 hours)
Page 424 of 487
-------
779 Model Run Time:
780 0-24 hours
781 User takes out scrapings after 210 and 480 minutes; emissions truncated.
Page 425 of 487
-------
782
783
784
785
786
787
788
789
790
791
792
793
794
795
796
797
798
799
800
801
802
803
804
805
806
807
808
809
810
811
812
813
814
815
816
817
NMPScenario G2. Floor, Spray-On, Workshop, User in ROHduring wait time, ROH=0.45
ACH, Workshop = 0.45 ACH (= 24.3 inVhr.), IZ = 107 mVhr., 0.5 Weight Fraction, Scrapings
removed after each scrape (WINDOWS CLOSED)
MCCEM Input Summary
Application Method: Spray-on
Volumes: Workshop volume = 54 m3
ROH volume = 492 - 54 = 438 m3
Airflows:
W orkshop-outdoors
24.3 m3/h
ROH-outdoors
197.1 m3/h (0.45 ACH)
Workshop-ROH
107 m3/h
NMP Mass Released:
Floor = 240 sq. ft. surface area
Applied product mass = 19,440 g (Application rate = 81 g/sf)
Overspray = 0.05*19,440 g = 972 g
Total Product Mass = 19,440 + 972 = 20,412 g
Total NMP Mass = 20,412 g x 0.5 (wt. fraction) = 10,206 g
Total NMP mass released (both exponentials) = 10,206g x 0.8695 (release fraction, theoretical)
8,874.1 g
Mass released per app = 4437.1 g
For each of the 2 applications:
ki = 32.83/hr.
% Mass for Exponential 1 = 7.0% of Total mass applied = 0.07/0.8695 = |8% of released NMP
Eoi = Mass * ki = 0.08*4437.1*32.83 = 11,653.6 g/hr. (NOTE: only k and Mass are needed as
inputs)
k2 = 0.00237/hr.
% Mass for Exponential 2 = 79.95% of applied NMP = 0.7995/0.8695 = 91.9% of released
NMP
E02 = Mass * k2 = 0.919*4437.1*0.00237 = 9.66 g/hr. (NOTE: only k and Mass are needed as
inputs)
Application Times and Activity Patterns:
Episode
Elapsed Time from Time Zero, Minutes (Product User
Location)
Apply 1
Wait 1
Scrape
1
Break
Apply 2
Wait 2
Scrape
2
G2) Floor, Spray-on, Workshop,
User in ROH during wait time,
0.45 ACH, 0.5 Weight Fraction,
WINDOWS CLOSED
0-60
(Wkshp
)
60-120
(ROH)
120-210
(Wkshp
)
210-270
(ROH)
270-330
(Wkshp
)
330-390
(ROH)
390-480
(Wkshp
)
User in ROH at the end of Scraping 2
User in ROH for the remainder of the run (16 hours)
Page 426 of 487
-------
818 Model Run Time:
819 0-24 hours
820 User takes out scrapings after 210 and 480 minutes; emissions truncated
Page 427 of 487
-------
821
822
823
824
825
826
827
828
829
830
831
832
833
834
835
836
837
838
839
840
841
842
843
844
845
846
847
848
849
850
851
852
853
854
NMP Scenario HI. Bathroom, Spray-On, Bathroom + Source Cloud, User in ROH during
wait time, R()H=0.18 A CI I, Bathroom = 0.18 ACH, IZ (source cloud/bathroom,
bathroom/ROH) = 80, 35 m3/hr., 0.5 Weight Fraction (Csat = 1013 mg/m3), Scrapings
removed after 2nd scrape (WINDOWS CLOSED, 2 applications)
MCCEM Input Summary
MCCEM saturation concentration constraint invoked at 1013 mg/m3
Application Method: Spray-on
Volumes: Bathroom Volume = 9 m3 (8 m3 after subtracting source cloud zone)
Source Cloud Volume = 1 m3
ROH volume = 492 - 9 = 483 m3
Airflows:
Bathroom-outdoors
1.6 m3/h
Source cloud - bathroom
80 m3/h
Source cloud - outdoors
0
ROH-outdoors
86.9 m3/h (0.18 ACH)
Bathroom-ROH
35 m3/h
NMP Mass Released:
Bathtub = 36 sq. ft. surface area
Applied product mass = 2,916 g (Application rate = 81 g/sf)
Overspray = 0.05*2,916 g = 145.8 g
Total Product Mass = 2,916 + 145.8 = 3,061.8 g
Total NMP Mass = 3,061.8 g x 0.5 (wt. fraction) = 1,530.9 g
Total NMP mass released (both exponentials) = 1530.9 x 0.8695 (release fraction, theoretical)
=1331.1 g
Mass released per app = 665.6 g
For each of the 2 applications:
ki = 32.83/hr.
% Mass for Exponential 1 = 7.0% of Total mass applied = 0.07/0.8695 = |8% of released NMP
Eoi = Mass * ki = 0.08*665.6*32.83 = 1748.1 g/hr. (NOTE: only k and Mass are needed as
inputs)
k2 = 0.00237/hr.
% Mass for Exponential 2 = 86.2% of applied NMP = 0.862/0.8695 = 99.2% of released NMP
E02 = Mass * ki = 0.919*665.6*0.00237 = 1.45 g/hr. (NOTE: only k and Mass are needed as
inputs)
Page 428 of 487
-------
855 Application Times and Activity Patterns:
Episode
Elapsed Time from Time Zero, Minutes (Product User
Location)
Apply 1
Wait 1
Scrape 1
Apply 2
Wait 2
Scrape 2
HI) Bathtub, Spray-On,
Bathroom + Source Cloud, User
in ROH during wait time, 0.18
ACH, 0.5 Wt. Fract.
0-9
(Src
Cloud)
9-39
(ROH)
39-75
(Src
Cloud)
75-84
(Src
Cloud)
84-114
(ROH)
114-150
(Src
Cloud)
856 User in ROH at the end of Scraping 2
857 User in ROH for the remainder of the run (21 hours, 30 minutes)
858
859 Model Run Time:
860 0-24 hours
861 User takes out scrapings after 150 minutes; emissions truncated.
862
Page 429 of 487
-------
863
864
865
866
867
868
869
870
871
872
873
874
875
876
877
878
879
880
881
882
883
884
885
886
887
888
889
890
891
892
893
894
895
896
NMP Scenario H2. Bathroom, Spray-On, Bathroom + Source Cloud, User in ROH during
wait time, R()H=0.18 A CI I, Bathroom = 0.18 ACH, IZ (source cloud/bathroom,
bathroom/ROH) = 80, 35 m3/hr., 0.5 Weight Fraction (Csat = 1013 mg/m3), Scrapings
removed after 2nd and 4th scrapes (WINDOWS CLOSED, 4 applications)
MCCEM Input Summary
MCCEM saturation concentration constraint invoked at 1013 mg/m3
Application Method: Spray-on
Volumes: Bathroom Volume = 9 m3 (8 m3 after subtracting source cloud zone)
Source Cloud Volume = 1 m3
ROH volume = 492 - 9 = 483 m3
Airflows:
Bathroom-outdoors
1.6 m3/h
Source cloud - bathroom
80 m3/h
Source cloud - outdoors
0
ROH-outdoors
86.9 m3/h (0.18 ACH)
Bathroom-ROH
35 m3/h
NMP Mass Released:
Bathtub = 36 sq. ft. surface area
Applied product mass = 2,916 g (Application rate = 81 g/sf)
Overspray = 0.05*2,916 g = 145.8 g
Total Product Mass = 2,916 + 145.8 = 3,061.8 g
Total NMP Mass = 3,061.8 g x 0.5 (wt. fraction) = 1,530.9 g
Total NMP mass released (both exponentials) = 1530.9 x 0.8695 (release fraction, theoretical)
=1331.1 g
Mass released per app = 665.6 g
For each of the 2 applications:
ki = 32.83/hr.
% Mass for Exponential 1 = 7.0% of Total mass applied = 0.07/0.8695 = |8% of released NMP
Eoi = Mass * ki = 0.08*665.6*32.83 = 1748.1 g/hr. (NOTE: only k and Mass are needed as
inputs)
k2 = 0.00237/hr.
% Mass for Exponential 2 = 86.2% of applied NMP = 0.862/0.8695 = 99.2% of released NMP
E02 = Mass * ki = 0.919*665.6*0.00237 = 1.45 g/hr. (NOTE: only k and Mass are needed as
inputs)
Page 430 of 487
-------
897
898
899
900
901
902
903
904
905
906
907
908
909
910
911
912
913
914
Application Times and Activity Patterns:
Episode
Bathtub, Spray-On, Bathroom +
Source Cloud, User in ROH
during wait time, 0.18 ACH, 0.5
Wt. Fract
Elapsed Time from Time Zero, Minutes (Product User
Location)
Apply
1&3
Wait
1&3
Scrape
1&3
Apply
2 &4
Wait
2&4
Scrape
2&4
E2) Bathtub, Brush-On, Bathroom + Source Cloud, User in
ROH during wait time, 0.18 ACH, 0.5 Weight Fraction
1st and 2nd Application
0-9
(Wkshp)
9-39
(ROH)
39-75
(Wkshp)
75-84
(Wkshp)
84-114
(ROH)
114-150
(Wkshp)
3rd and 4th Application
210-219
(Wkshp)
219-249
(ROH)
249-285
(Wkshp)
285-294
(Wkshp)
294-324
(ROH)
324-360
(Wkshp)
User in ROH at the end of Scraping 2 and 4
User in ROH for the remainder of the run (18 hours)
Model Run Time:
0-24 hours
User takes out scrapings after 150 and 360 minutes; emissions truncated.
Appendix B - Spreadsheet: Details of NMP Exposure Model Results
See the separate spreadsheet loaded into this docket (EPA-HQ-OPPT-2016-0231) for the zone-
specific and exposure concentrations predicted by MCCEM.
Appendix C - Spreadsheet: NMP Risk Estimation
See the separate spreadsheet loaded into this docket (EPA-HQ-OPPT-2016-0231) for risk
calculations.
Appendix D
Table D-l. Eight-hour TWA exposures for additional scenarios
Scenario
lndi\ iclnal
S-l lour TWA exposure
mu in'
ppm
Al. Coffee Table, Brush Application in Workshop,
Windows Open
User
2.2
0.5
Non-User
1.5
0.4
A2. Coffee Table, Brush Application in Workshop,
Windows Closed
User
3.1
0.8
Non-User
2.2
0.5
Bl. Chest, Brush Application in Workshop, Windows
Open
User
7.7
1.9
Non-User
4.3
1.1
B2. Chest, Brush Application in Workshop, Windows
Closed
User
10.7
2.6
Non-User
6.1
1.5
Page 431 of 487
-------
Scenario
1 ncli\ iclnal
S-l lour TWA exposure
mu in'
ppm
CI. Dining table and chairs, Brush Application in
Workshop, Windows Open
User
70.2
17.3
Non-User
24.7
6.1
C2. Dining table and chairs, Brush Application in
Workshop, Windows Closed
User
97.7
24.1
Non-User
35.0
8.6
C3. Dining table and chairs, Brush Application in
Workshop, Windows Open, Scrapings removed after
each scrap
User
54.5
13.4
Non-User
19.1
4.7
Dl. Floors, Roller Application in Workshop, Windows
Open
User
110.9
27.4
Non-User
45.0
11.1
D2. Floors, Roller Application in Workshop, Windows
Closed
User
150.6
37.1
Non-User
63.7
15.7
El. Bathtub, Brush Application in Bathroom, Csat =
1,013 mg/m3, 2 Applications
User
78.8
19.4
Non-User
20.4
5.0
E2. Bathtub, Brush Application in Bathroom, Csat =
1,013 mg/m3, 4 Applications
User
148.9
36.7
Non-User
35.7
8.8
Fl. Dining table and chairs, Spray Application in
Workshop, Windows Open
User
227.1
56.0
Non-User
94.8
23.4
F2. Dining table and chairs, Spray Application in
Workshop, Windows Closed
User
319.3
78.8
Non-User
133.8
33.0
F3. Dining table and chairs, Spray Application in
Workshop, Windows Open
User
218.4
53.9
Non-User
92.1
22.7
Gl. Floors, Spray Application in Workshop, Windows
Open
User
540.1
133.2
Non-User
214.2
52.8
G2. Floors, Spray Application in Workshop, Windows
Closed
User
724.6
178.7
Non-User
303.1
74.8
HI. Bathtub, Spray Application in Bathroom, Csat =
1,013 mg/m3, 2 Applications
User
339.4
83.7
Non-User
109.2
26.9
H2. Bathtub, Spray Application in Bathroom, Csat =
1,013 mg/m3, 4 Applications
User
640.9
158.1
Non-User
192.8
47.6
915 Csat = Saturation Concentration
Page 432 of 487
-------
916
917
Page 433 of 487
-------
918
919
920
921
922
923
924
925
926
927
928
929
930
931
932
933
934
Appendix G
PEER REVIEW DRAFT, DO NOT CITE OR QUOTE
ENVIRONMENTAL HAZARDS
EPA has reviewed acceptable ecotoxicity studies for NMP according to the data quality evaluation
criteria found in The Application of Systematic Review in TSCA Risk Evaluations ( j).
The results of these ecotoxicity study evaluations can be found in NMP (872- 'vstematic Review:
Supplemental File for the TSCA Risk Evaluation Document. The data quality evaluation indicated these
studies are of high confidence and are used to characterize the environmental hazards of NMP. These
studies support that hazard of NMP to aquatic organisms is low and that no further evaluation is
required.
The acceptable aquatic studies that were evaluated for NMP are summarized in TableApx G-l. The
hazard of these studies has been reported (U.S. EPA. 2006b). (OECD 1:007b). (Danish Ministry of the
Environment. 2.015). ( 1015) and (Envirp- ;n . J as stated in llie NMP Problem
Fprmulatipn (•. ' \ T \
Table Apx G-l. On-topic aquatic toxicity studies llial were evaluated for N-Melhvlpvrrolidone
Tesl Species
Ircsli/
Siili
Wilier
Diii'iilion
I'.ndpoinl
( onceiil r;i 1 ion(s)
lesl
An;il\sis
r.lTccl(s)
References
Diilii
Qu;ili(\
l-'.\iiliiiiiion
/7 s//
Fathead
minnow
(Pimephales
promelas)
Fresh
96-h
LCso = 1072
ms'l.
38^.(48. 1080. ISOO.
-ooo. 5ooo mu 1.
Sialic.
Nominal
Mortality
( )
High
Rainbow trout
(Salmo
Gairdneri)
Fresh
•K-li
I.( -H48
mu 1.
778, 1296,2160.3600,
6000, 10,000 mg/L
Static,
Nominal
Mortality
( )
High
Rainbow trout
(Oncorhynchus
mykiss)
Fresli
or.-h
I.( 5(H)
nm 1.
o. L
Static,
Nominal
Mortality
(BASF AG.
1983)
High
Orfe (Lcuciscus
idus)
Fresh
•K-li
I.( 411-0
mu 1.
100.215,464, 1000,
2 150. 4640, 10,000 mg/L
Static,
Nominal
Mortality
(BASF AG.
1986)
High
Aquatic Invertebrates
Water Ilea
(Daphnia
magna)
Fresh
48-h
I.C 4897
iii-j/L
389, 648, 1080, 1800,
3000, 5000, 8333 mg/L
Static,
Nominal
Mortality
( )
High
Water flea
(Daphnia
magna)
Fresli
:i-da>
\OliC=12.5
"tig/L
L(JEC= 25
mg/L
0.39,0.78, 1.56,3.13,
6.25, 12.5, 25, 50, 100
mg/L
Static,
Nominal
Reproduct
ion
(BA
2001)-
High
Grass shrimp
(Palaemonetes
vulgaris)
Salt
96-h
LCscF 1107
mg/L
360, 600, 1000, 1667,
2775 mg/L
Static,
Nominal
Mortality
( )
High
Scud
('Gammarus sp)
Fresh
96-h
LC5o= 4655
mg/L
389, 648, 1080, 1800,
3000, 5000, 8333 mg/L
Static,
Nominal
Mortality
( )
High
Mud crabs
(Neopanope
texana sayi)
Salt
96-h
LC50= 15 85
mg/L
360, 600, 1000, 1667,
2775 mg/L
Static,
Nominal
Mortality
( )
High
Algae
Page 434 pf 487
-------
PEER REVIEW DRAFT, DO NOT CITE OR QUOTE
Tesl Species
Ircsli/
Siili
Wilier
Diii'iilion
I'.ndpoinl
( onceiil r;i 1 ion(s)
Tesl
An;il\sis
r.lTccl(s)
References
Diilii
Qu;ili(>
r.\;iliiiilion
Algae
(Scenedemus
subspicatus)
Fresh
72-h
EbC5o=600
ErC50=673
mg/L
7.8, 15.6, 31.3,62.5,
125, 250, 500 mg/L
Static,
Nominal
Biomass
Growth
rate
(BASF AG.
1989)
High
Algae
(Scenedemus
subspicatus)
Fresh
72-h
LOEC=250
NOEC=125
7.8, 15.6, 31.3,62.5,
125, 250, 500 mg/L
Static,
Nominal
Growth
(BASF AG.
1989)
High
93 5 a Reservation of Rights: BASF has agreed to share this toxicity study report ("Study Report") with US EPA, at its written request, for EPA's use in
936 implementing a statutory requirement of the Toxic Substances Control Act ("TSCA "). Every other use, exploitation, reproduction, distribution, publication
937 or submission to any other party requires BASF's written permission, except as otherwise provided by law. The submission of this Study Report to a public
938 docket maintained by the United States Environmental Protection Agency is not a waiver of BASF's ownership rights. No consent is granted for any other
939 third-party use of this Study Report for any purpose, in any jurisdiction. Specifically, and by example, no consent is granted allowing the use of this Study
940 Report by a private entity in requesting any regulatory status, registration or other approval or benefit, whether international, national, state or local,
941 including but not limited to the Regulation Evaluation Authorization and Restriction of Chemicals ("REACH") regulation administered by European
942 Chemicals Agency ("ECHA"), an agency of the European Union.
Page 435 of 487
-------
PEER REVIEW DRAFT, DO NOT CITE OR QUOTE
943
944
945
946
947
948
949
Appendix H HUMAN HEALTH HAZARDS
H.l Hazard and Data Evaluation Summaries
H.l.l Hazard and Data Evaluation Summary for Acute and Short-term Oral Exposure Studies
Table Apx H-l. E
azard and Data Evaluation Summary for Acute and Short-term Oral Exposure Studies
T;il»Cl
Orgsin/
S\s(cm
SiihIj
Tj pc
Species. S(
Sex
(\ii m l>cr/» i
'iiin.
'iher. Male
(5)
u. I4<>. 4:i>.
i:u. :ui<>
mu ku-hu da>
Hi.
IS. and
3U,UU<> ppni)
4 weeks
\() KEL =
42') ing/kg -
hw/day
NO A F.I. =
429 mg/kg -
bw/day
Decreased body weight and
altered testes and liver weights
were observed at 1234 mg/kg-
bw/day and above.
Degeneration/atrophy of
testicular seminiferous tubules
were observed 1/5 males at
1234 mg/kg-bw/day and in 5/5
at 2019 mg/kg-bw/day.
Increased incidence of
centrilobular hepatocellular
hypertrophy and decreased
serum glucose were observed
at 1234 mg/kg-bw/day and
above.
Malek et al
(19971
High
Page 436 of 487
-------
PEER REVIEW DRAFT, DO NOT CITE OR QUOTE
T;irjie(
Origin/
Sjslcm
Sludj
Tj pC
Species. Sii'iiin.
Sc\
(Niimhcr/^roup)
Doses/
( oiicciilriilioiis
Diinilioii
Author
Kcporlcd
r.lTccl Dose
or (oiiccii-
li'iilion
(NO AII..
1.OA I'll..
I.( 50)
(Se\)
l-'.PA
1 den li lied
r.lTccl Dose
or (onccii-
li'iilion
(NOAII..
1.OA I'll..
I .( 50)
(Sex)
KITecl
Reference
Diilii
Qu;ilil\
l'l\iilu;ilion
Body
Weight
Short-
term
(1-30
days)
Rat, Other Female
(5)
0, 161,493,
1548, 2268
mg/kg-bw/day
(0, 2000, 6OO11.
18,000, and
30,000 ppmi
4 weeks
NO A F.I. =
154S mcTxC
- hw da>
N()\i:i.
154S mg, ku
- hw/da>
Decreased body wciuhl and
body weight gain w ere
observed at 2268 mg/kg-
bw/day. Increased serum total
protein, albumin, and
cholesterol levels and
increased incidence of
ceiiirilobular hepatocellular
h> peiirophy, hypocellular bone
marrow, and thymic atrophy
w ere also observed at 2268
mg/kg-bw/day.
Malek et al
(1997)
High
Body
Weight
Short-
term
(1-30
days)
Mouse, B6C3F1,
Female (5)
u. ISO. 920.
2TII. 4060
mu ku-h\v'da>
(0, 50(i. :5()()
"5()o. | o.ooo
ppun
4 weeks
\ol
kepoiied
\( )AEL =
4o(>0 mg/kg
- hw/day
No exposure-related effects
NMP
Producers
Group
(1994)
High
Body
Weight
Short-
term
(1-30
days)
Mouse 1 !<>C3F1,
Male ( 5)
o. 1 "o. ":o.
:i ^o. :(,-o
mg/ku-hw da>
(0, 5oo. 25oo
750o. lo.ooo
ppmi
4 weeks
Not
Reported
NO A F.I. =
2670 mg/kg
- bw/day
No exposure-related effects
NMP
Producers
Group
(1994)
High
Clinical
Chemistry/
Biochemica
1
Short-
term
(1-30
days)
Rat Sprague-
Dawley, Male (5)
o. 25o. 5oo.
1 11 u ku-
hw. da\
5 days/
week for 5
weeks
Not
Reported
NO A F.I. =
250 mg/kg -
bw/day
Decreased serum creatinine
Gopinathan
et al (201_3)
Medium
Page 437 of 487
-------
PEER REVIEW DRAFT, DO NOT CITE OR QUOTE
T;irjie(
Origin/
Sjslcm
Sludj
Tj pC
Species. Sii'iiin.
Sc\
(Niimhcr/^roup)
Doses/
( oiicciilriilioiis
Diinilioii
Author
Kcporlcd
r.lTccl Dose
or (oiiccii-
li'iilion
(NO AII..
1.OA I'll..
I .( 50)
(Se\)
r.PA
1 den li lied
r.lTccl Dose
or (onccii-
li'iilion
(NOAII..
1.OA I'll..
I .( 50)
(Sex)
mied
Reference
Diilii
Qu;ilil\
l'l\iilu;ilion
Endocrine
Short-
term
(1-30
days)
Rat, Other, Female
(5)
0, 161,493,
1548, 2268
mg/kg-bw/day
(0, 2000, 6000.
18000, and
30000 ppm)
4 weeks
NO A F.I. =
1548 nig/kg
- bw/dav
\o\i:i.
1548 mg, ku
- bw/da>
Decreased body wciuhl and
body weight gain u ere
observed at 2268 mg/kg-
bw/day. Increased serum total
protein, albumin, and
cholesterol levels and
increased incidence of
ceiiirilobular hepatocellular
h> peiirophy, hypocellular bone
marrow, and thymic atrophy
u ere also observed at 2268
mg/kg-bw/day.
Malek et al
(1997)
High
Hemato-
logical and
Immune
Short-
term
(1-30
days)
Rat, Sprague-
Dawley, Male (5)
(i. 25(i. 5iio.
1 11 u ku-
h\\ da>
5 days/
week for 5
weeks
Nol
Repmied
\OAEL =
H KM) mg/kg
- bw/day
No mortalities occurred and no
changes were reported for
hematology parameters or liver
or spleen weights.
Gopinathan
et al (201_3)
Medium
Hepatic
Short-
term
(1-30
days)
Rat. Spragne-
Dawley. Male (5)
ii. 25(i. 5iio.
1 Ilg k g-
h\\ da>
5 days/
week for 5
weeks
Not
Reported
NO A F.I. =
1000 mg/kg
- bw/day
No mortalities occurred and no
changes were reported for
hematology parameters or liver
or spleen weights.
Gopinathan
et al (2013)
Medium
Page 438 of 487
-------
PEER REVIEW DRAFT, DO NOT CITE OR QUOTE
T;irjie(
Origin/
Sjslcm
Sludj
Tj pC
Species. Sii'iiin.
Sc\
(Niimhcr/^roup)
Doses/
( oiicciilriilioiis
Diinilioii
Author
Kcporlcd
r.lTccl Dose
or (oiiccii-
li'iilion
(NO AII..
1.OA I'll..
I.( 50)
(Se\)
l-'.PA
1 den li lied
r.lTccl Dose
or (onccii-
li'iilion
(NOAII..
1.OA I'll..
I .( 50)
(Sex)
KITecl
Reference
Diilii
Qu;ilil\
l'l\iilu;ilion
Hepatic
Short-
term
(1-30
days)
Rat, Other Female
(5)
0, 161,493,
1548, 2268
mg/kg-bw/day
(0, 2000, 6OO11.
18,000, and
30,000 ppmi
4 weeks
NO A F.I. =
154S mils
- hw da>
N()\i:i.
154S mg, ku
- hw/da>
Decreased body wciuhl and
body weight gain w ere
observed at 2268 mg/kg-
bw/day. Increased serum total
protein, albumin, and
cholesterol levels and
increased incidence of
ceiiirilobular hepatocellular
h> peiirophy, hypocellular bone
marrow, and thymic atrophy
w ere also observed at 2268
mg/kg-bw/day.
Malek et al
(1997)
High
Hepatic
Short-
term
(1-30
days)
Mouse, B6C3F1,
Female (5)
u. ISO. 920.
2TII. 4060
mu ku-h\v'da>
(0, 50(i. :5()()
"5()o. | o.ooo
ppun
4 weeks
\ol
kepoiied
\( )AEL =
4o(>0 mg/kg
- hw/day
No exposure-related effects
NMP
Producers
Group
(1994)
High
Hepatic
Short-
term
(1-30
days)
Mouse. 1 !<>C3F1,
Male (5)
o. 1 "o. ":o.
:i ^o. :(,-o
mg/ku-hw da>
(0, 5oo. 25oo
750o. lo.ooo
ppmi
4 weeks
Not
Reported
NO A F.I. =
2670 mg/kg
- bw/day
No exposure-related effects
NMP
Producers
Group
(1994)
High
Mortality
Short-
term
(1-30
days)
Rat, Sprague-
Dawley, Male (5)
o. 25o. 5oo.
1 11 u ku-
hw, da\
5 days/
week for 5
weeks
Not
Reported
NO A F.I. =
1000 mg/kg
- bw/day
No mortalities occurred and no
changes were reported for
hematology parameters or liver
or spleen weights.
Gopinathan
et al (2013)
Medium
Page 439 of 487
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PEER REVIEW DRAFT, DO NOT CITE OR QUOTE
T;irjie(
Origin/
Sjslcm
Sludj
Tj pC
Species. Sir;iin.
Sc\
(Niimhcr/^roup)
Doses/
( oiicciilriilioiis
Diinilioii
Author
Kcporlcd
r.lTccl Dose
or (oiiccii-
li'iilion
(NO AII..
1.OA I'll..
I.C50)
(Sc\)
l-'.PA
1 den li lied
lllTecl Dose
or (onccii-
li'iilion
(NOAII..
1.OA I'll..
I .( 50)
(Sex)
KITecl
Reference
Diilii
Qu;ilil\
l'l\iilu;ilion
Mortality
Short-
term
(1-30
days)
Mouse, B6C3F1,
Male (5)
0, 130, 720,
2130, 2670
mg/kg-bw/day
(0, 500, 2500,
7500, 10000
ppm)
4 weeks
NO A F.I.
0.048
\o\i:i.
1 125 I11U ku
- h\\ dav
Mortality in a male mouse iliat
also showed renal effects,
death was considered related to
treatment.
Malek et al
(1997)
High
Mortality
Short-
term
(1-30
days)
Mouse, B6C3F1,
Female (5)
0, 180, 920,
2970, 4060
mg/kg-bw/day
(0, 500, 2500.
7500, 10,000
ppm >
4 weeks
\nl
kepniied
\o\i:i.
40(iO niii ku
- h\\ dav
No c\posure-related effects
NMP
Producers
Group
(1994)
High
Mortality
Short-
term
(1-30
days)
Mouse, B6C3F1,
Male (5)
(I. no. 720.
:nn. 2670
mg ku-hw dav
(0, 5iio. 25ii()
"5oo. | o.ooo
ppim
4 weeks
Not
Reported
NO A F.I. =
2670 mg/kg
- bw/day
No exposure-related effects
NMP
Producers
Group
0994)
High
Not
Reported
Short-
term
(1-30
days)
Ral. Sprague-
1 )a\\ lev. Male (5)
o. 25o. 5oo.
1 ku-
bv\ dav
5 dav s
week I'or5
weeks
Not
Reported
NO A F.I. =
250 mg/kg -
bw/day
Decreased serum creatinine
Gopinathan
et al (2013)
Medium
Not
Reported
Short-
term
(1-30
days)
Rat, Sprague-
Dawley, Male (5)
o. 250, 5oo.
looo m- ku-
hw'da>
5 days/
week for 5
weeks
Not
Reported
NOAEL =
250 mg/kg -
bw/day
Decreased serum creatinine
Gopinathan
et al (2013)
Medium
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T;irjie(
Origin/
S\slem
Sludj
Tj |)0
Species. Sir;iin.
Sox
(Niimhcr/^roup)
Doses/
( onccnlriilions
Diinilioii
Author
Keporlcri
If loci Dose
or ('oiiccu-
li'iilion
(NO AII..
1.OA I'll..
I.C50)
(Sex)
I.PA
1 (leu li fieri
HITccl Dose
or ('oiiccu-
li'iilion
(NOAII..
1.OA I'll..
I .( 50)
(Sex)
11 f loci
Reference
Diilii
Qu;ilil\
l'l\iilu;ilion
Renal
Short-
term
(1-30
days)
Rat, Sprague-
Dawley, Male (5)
0, 250, 500,
1000 mg/kg-
bw/day
5 d;i\ s
week fur 5
weeks
Vol
keporied
Not
Reported
Mottled kidneys were reported
bilaterally with a comhined
incidence in all dose groups
(250, 500, and 1000 mg/kg-
bw/day) of 8/15. This was not
observed in controls. No
ekinges were reported for
mrilie chemistry parameters or
kidney weights. Incidences of
mottled kidneys for each dose
uioup were not reported, so I
did not assign a NOAEL or
LOAEL for renal effects.
Gopinathan
et al (2013)
Medium
Renal
Short-
term
(1-30
days)
Mouse, B6C3F1,
Female (5)
ii. ISO.
2l>~(). 4<>(><>
mg/ku-hw d;i\
(0. 5(1(1. 25(10
"75(>(1. |(i.(i(i(i
ppnn
4 weeks
\o\i:i.
l>2o mu ku -
hw da>
\< )AEL =
l>2o mg/kg -
hw/day
Dark yellow urine in all
animals at Dose 3, 4, and 5.
Cloudy swelling of the distal
renal tubule in 3/5 females at
Dose 5
NMP
Producers
Group
(1994)
High
Renal
Short-
term
(1-30
days)
Mouse. IJ6CFI.
\1;ile (5)
(i. 1 '(>. ~2(i.
21 "o. 2(>~(i
mg,ku-hw d;i>
(0, 500, 25()().
"500, 10.
ppnn
4 weeks
NO A F.I. =
720 mg/kg -
bw/day
NO A F.I. =
720 mg/kg -
bw/day
Dark yellow urine in all
animals at Dose 3, 4, and 5.
Cloudy swelling of the distal
renal tubule in 2/5 males at
Dose 4. and 4/5 males at Dose
5
NMP
Producers
Group
(1994)
High
950
951
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952
953
954
955
Target
Organ/
System
Sluilv
Type
Species,
Strain, Sex
(Nil in her/
group)
Doses/
Concen-
trations
Duration
Author
Reported
I! fleet
Dose or
Concen-
tration
(\oai:i„
i oai:l.
IX 50)
(Sex)
i:i»a
1 den ti lied
I! ITcd Dose
or Concen-
tration
(\oai:i ..
I.OAKI..
LC50)
(Sex)
KITect Measured
Reference
Data
Quality
K\ alualion
Body
Weight
Repro-
ductive
Rat, Male
(22-24)
0. 100. 300.
11 ij kg-
b\\ da\
5 days/
week for
10 weeks
prior to
maling and
1 week
during
nulling
Not
Re polled
NOAHL
300 mg/kg -
bw/day
Bod> weight decrement of
at least 10%
Sitarek et al
(2008)
High
Growth
and
Develop-
ment
Repro-
ductive
Rat. Other.
Male (22-
24)
0, 100, 300,
1000 mg/kg-
bw/da\
5 da\ s/
week for
10 weeks
prior to
mating and
1 week
during
mating
Not
Reported
NOAEL =
100 mg/kg -
bw/day
Decreased offspring
viability through PND4
Sitarek et al
(2008)
High
H.1.2 Hazard and Data Evaluation Summary for Reproductive and Developmental Oral Exposure Studies
Table Apx H-2. Hazard and Data Evaluation Summary for Reproductive and Developmental Oral Exposure Studies
Page 442 of 487
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T:ir»et
()r»:in/
System
Sluilv
Type
Species,
Slrsiin. Sex
(Nil m her/
"roup)
Doses/
(onccn-
Initions
Duriilion
Author
Report eil
Effect
Dose or
C'oncen-
tnition
(\OAEL,
LOAEL,
IX 50)
(Sex)
i:i»a
1 den ti Tied
Effect Dose
or Coiicen-
triition
(\OAEL.
I.OAEL.
L( 50)
(Sex)
Effect Mejisureil
Reference
l):it;i
Qiiiililv
E\ iiliiiition
Growth
and
Develop-
ment
Repro-
ductive
Rat, Wistar,
Female (22-
28)
0, 150, 450,
1000 mg/kg-
bw/day
5 days/
week for
two weeks
before
mating,
during
gestation
and
laclalion
LOAEL =
I5()
niij kg-
h\\ da\
T.OAEL
150 mg/kg-
b\\ 'da\
Significant decrease in pup
sui'\ ival within three weeks
of birth at all doses.
Sitarek et al
(2012)
High
Repro-
ductive
Subchronic
(30-90
days)
Dog,
T3eag1e.
Bolh
(6/sex)
i). 24. 75.
24(i niij kg-
h\\ da\ in
males. <). 24.
7<\ 24h
mg kg-
h\\ da\ in
females
(actual
concenlialio
IIS)
13 weeks
Not
Reported
\OAEL =
246 mg/kg -
bw/day
No effects on reproductive
organs, hematological/
immune, body weight,
relative organ (liver,
kidney, spleen, heart,
thyroid, adrenal glands,
brain, and pituitary)
weights.
Becci et al
(1983)
High
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T:ir»et
Or»:in/
System
Sluilv
Type
Species,
Slrsiin. Sex
(Nil m her/
"roup)
Doses/
(onccn-
Initions
Duriilion
Author
Reported
Effect
Dose or
C'oncen-
tnition
(\OAEL,
I.OAEL,
IX 50)
(Sex)
i:i»a
1 den ti Tied
Effect Dose
or Coiicen-
l ml ion
(NOAEI..
I.OAEL.
IX 50)
(Sex)
Effect Mcjisured
Reference
l):it;i
Qiiiility
E\ iiliiiition
Repro-
ductive
Short-term
(1-30 days)
Rat, Other,
Male (5)
0, 149, 429,
1234, 2019
mg/kg-
bw/da\ (ii.
2000.
IS. Odd.
3o.( ii id ppm)
4 weeks
\o\i:i.
42l> nig kg
- bvv da\
\o\i:i.
42l> nig kg -
bvv.dav
Decreased body weight
and altered testes and liver
\\ eights were observed at
1234 mg/kg-bw/day and
above.
Degeneration/atrophy of
k'sticular seminiferous
tubules were observed 1/5
males at 1234 mg/kg-
bw/day and in 5/5 at 2019
mg/kg-bw/day. Increased
incidence of centrilobular
hepatocellular hypertrophy
and decreased serum
glucose were observed at
1234 mg/kg-bw/day and
above.
Malek et al
(1997)
High
Repro-
ductive
Subchronic
(30-90
days)
Ral. Oilier.
Male (Hi)
1. IM. 433.
1057 mg/kg -
bw/day ((>.
3000, 7500,
IS. ppm)
90 da> s
Not
Reported
NOAEL =
1057 mg/kg
- bw/day
No adverse effects.
Malley et al
(1999)
High
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PEER REVIEW DRAFT, DO NOT CITE OR QUOTE
T:ir»et
()r»:in/
System
Sluilv
Type
Species,
Slrsiin. Sex
(Nil m her/
"roup)
Doses/
(onccn-
Initions
Duriilion
Author
Report eil
Effect
Dose or
C'oncen-
tnition
(NOAEL,
LOAEL,
IX 50)
(Sex)
i:i»a
1 den ti Tied
Effect Dose
or Coiicen-
l ml ion
(NOAEL,
LOAEL,
I.C50)
(Sex)
Effect Mejisureil
Reference
l):it;i
Qiiiililv
E\ iiliiiition
Repro-
ductive
Subchronic
(30-90
days)
Mouse,
Both
(20/sex)
0, 277, 619,
1931 mg/kg -
bw/day (0,
1000, 2500,
7500 ppm)
90 da\ s
Not
Reported
\o\i:i.
193 1 mg kg
- bw da\
No adverse effects.
Malley et al
(1999)
High
Repro-
ductive
Chronic
(>90 days)
Rat, Other,
Male (62)
0, 66.4, 207,
678 mg kg-
bw/da\ (ii.
1600. 5()()().
15. ppm)
2 \ ears
Not
Re polled
NOAEL
207 mg/kg -
bw/day
Biliateral
degeneration/atrophy of
seminiferous tubules in the
tests, bilateral
oligospermia/germ cell
debris in the epididymites,
centrilobular fatty change
in the liver
Malley et al
(2001)
High
Repro-
ductive
Chronic
(>90 da\ s)
Rat. Other.
I'emale (62)
o. 87 8. 2X3.
mg kg-
liw da\ (0.
1(>00. 5000.
15,000 ppm)
2 \ ears
Not
Reported
NOAEL =
939 mg/kg -
bw/day
No exposure-related
adverse effects
Malley et al
(2001)
High
Repro-
ductive
Chronic
(>90 days)
Mouse.
B6C3F1.
Male (50)
0. 89, 173.
1089 mg/kg-
bw/dav (0.
600. 1200,
7200 ppm)
18 months
Not
Reported
NOAEL =
1089 mg/kg
- bw/day
No adverse effects
Malley et al
(2001)
High
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T:ir»et
()r»:in/
System
Sluilv
Type
Species,
Slrsiin. Sex
(Nil m her/
"roup)
Doses/
(onccn-
Initions
Duriilion
Author
Reported
I! fleet
Dose or
('onccn-
tnition
(\OAKL,
I.OAKL,
IX 50)
(Sex)
i:i»a
Identified
I! lied Dose
or Coiicen-
triition
(NOAM..
I.OAKL,
l.( 50)
(Sex)
KITcct Mejisured
Reference
l):it;i
Quality
K\ iiliiiition
Repro-
ductive
Chronic
(>90 days)
Mouse,
B6C3F1,
Female (50)
0, 115,221,
1399 mg/kg-
bw/day (0,
600, 1200,
7200 ppm)
18 months
Not
Reported
\o.\i:i.
1399 mg kg
- h\\ da\
No adverse effects
Malley et al
(2001)
High
Repro-
ductive
Repro-
ductive
Rat, Other,
Male (22-
24)
0, 100, 300,
1000 mg/kg-
b\\ da\
5 days/
week
Not
Reported
\OAEL
1 mi mg kg -
bw da\
Decreased offspring
\i ability through PND4
Sitarek et al
(2008)
High
Repro-
ductive
Short-term
(1-30 days)
Mouse,
B6C3F1.
Male (5)
(). I3ii. 72H.
213(1. >7"
mg kg-
hw da\ Hi.
5()(). :'5oo.
"5oo.
ppun
4 weeks
Not
Reported
NOAEL =
2670 mg/kg
- bw/day
No exposure-related effects
NMP
Producers
Group/
BASF
(1994)
High
Repro-
ductive
Repro-
ductive
Ral. Wislar.
Female* 22-
28)
0, 150, 45ii.
1 ill id mg/kg-
hw/dav
5 da\ s
week fur
two weeks
helbre
mating,
during
gestation
and
lactation
NOAEL =
150
mg/kg-
bw/day
NOAEL =
150 mg/kg-
bw/day
Significantly decreased
female fertility index
Sitarek et al
(2012)
High
Page 446 of 487
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PEER REVIEW DRAFT, DO NOT CITE OR QUOTE
T:ir»et
()r»:in/
System
Sluilv
Typo
Species,
Slrsiin. Sex
(Nil m her/
"roup)
Doses/
(onccn-
Initions
Duriilion
Author
Report eil
Effect
Dose or
C'oncen-
tnition
(\OAEL,
I.OAEL.
IX 50)
(Sex)
i:i»a
1 den ti Tied
Effect Dose
or Coiicen-
l ml ion
(\OAEI „
I.OAEL,
l.( 50)
(Sex)
Effect Mejisureil
Reference
l):it;i
Qiiiility
E\ iiliiiition
Thyroid
Repro-
ductive
Rat, Male,
(22-24)
0, 100, 300,
1000 mg/kg-
bw/day
5 days/
week for
10 weeks
prior to
mating and
1 week
during
mating
Not
Re ported
noai:l
3(h) mg/kij -
ln\/da\
Significantly increased
absolute and relative
thyroid weight.
Sitarek et al
(2008)
High
956
957
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958
959
960
961
H.1.3 Hazard and Data Evaluation Summary for Reproductive and Developmental Inhalation Exposure Studies
Table Apx H-3. Hazard and Data Evaluation Summary for Reproductive and Developmental Inhalation Exposure Studies
Tsir»et
()r»;in/
System
Study Type
Species,
St I'iiin.
Sex
(Nil m her
/»roup)
Doses/
Con cen-
lriilions
Duriilion
Author
Reported
K fleet
Dose or
Concen-
Imlion
(NOAI-II..
LOAM..
I.C'50)
(Sex)
i:i»a
Identified
L lied
Dose or
Concen-
t nil ion
(NOALL.
LOAM..
IX 50)
(Sex)
Kfled Me:isured
Reference
Diitii
Qiiiililv
K\:ilu;ilion
Body
Weight
Developmental
Rat,
Sprague-
Dawley,
Female
(25-26)
0, 122. 243.
487 niij in
s week
lor 15 weeks
\o\i:i.
122 niij in
\o\i:i. =
I 22 IllL! Ill
I () AI !L for decreased
malernal weight gain at
243 mg/m3. Maternal food
i utake also decreased at
487 mg/m3+.
Saillenfait et
al (2003)
High
Growth
and
Develop
ment
Reproductive
Rat
Other.
Bolli
(I DM and
2 • > I")
i). 42. 2"ft.
472 mil: in
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PEER REVIEW DRAFT, DO NOT CITE OR QUOTE
Tsirget
()r»:in/
System
Study Type
Species,
Si niin.
Sex
(Nil in her
/group)
Doses/
Coiicen-
tnilioiis
Dunition
Author
Reported
K fleet
Dose or
C'oncen-
triition
(\OAKL,
LOAM..
I.C50)
(Sex)
i:i\\
1 denti Tied
LITect
Dose or
C'ouceii-
tnition
(NOALL.
LOALL.
I.C'50)
(Sex)
LITect Measured
Reference
l);itii
Quality
L\;ilu;ilion
Growth
and
Develop
ment
Developmental
Rat,
Other,
Female
(25)
0, 100, 360
mij'm3
6 hours/ day
7 days/ week
lor 11) weeks
Not
Reported
\o\i:i.
360 niij in
No effects on uterine or
liHer parameters, fetal
weight or length, or
incidence of gross, soft
tissue, or skeletal
anomalies
Lee et al
(1987)
High
Neuro-
logical/
Behavior
Reproductive
Rat,
Other,
Both
(10M and
20F)
i). 42.
472 iiil: in
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PEER REVIEW DRAFT, DO NOT CITE OR QUOTE
Tsirget
()r»:in/
System
Study Type
Species,
Si niin.
Sex
(Nil m her
/group)
Doses/
Coiiceu-
tnilioiis
Dunitioii
Author
Reported
K fleet
Dose or
C'oncen-
triition
(\OAKL,
LOAM..
IX 50)
(Sex)
i:i\\
1 clent i I'ietl
KITect
Dose or
C'ouceii-
tnition
(NOAKL.
LOAKL.
I.C'50)
(Sex)
Kl'fect Meiisured
Reference
Diilii
Qiiiility
K\;ilu;ilion
Repro-
ductive
Reproductive
Rat,
Other,
Both
(10M and
20F)
0, 42. 206.
472 mg/m3
6 hours/ da\
7 days/ w cck
for 143
weeks
NOAEL =
472 mg/m;
NOALI.
472 mg in
\o significant difference
i ti reproductive
|ie rformance or adult body
weight. Study notes
condensation on inside of
high dose chambers,
w hich precluded
achieving target
concentration of 527
mg/m3.
Solomon et
al 0995)
High
Repro-
ductive
Chronic (>90
days)
Rat, Cij:
CD(SD),
Both
(120)
(), 41. 405
mg/m3
6 hours/
da\ 5 da\ s'
week
Not
Reported
NOAEL =
41 mg/m3
Mammary gland
hyperplasia
DuPont
(1982.)
Medium
Repro-
ductive
Chronic (>90
days)
Rat. Crj:
CD(SD).
Both
(120)
0.41.405
mg/nr
() hours day
5da\s week
Not
Reported
NOAEL =
405 mg/m3
No adverse effects (based
on histopathology of
epididymites and prostate)
DuPont
(1982)
Medium
962
963
964
965
966
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967 H.1.4 Hazard and Data Evaluation Summary for Reproductive and Developmental Dermal Exposure Studies
968
969 Table Apx H-4. Hazard and Data Evaluation Summary for Reproductive and Developmental Dermal Exposure Studies
970
Tsirget
Or»:in/
System
Sluilv Typo
Species,
Slniiii.
Sex
(Nil m her/
»roup)
Doses/
Conccnlnilions
Diii'iilion
Author
Reported
KITect
Dose or
Concent r;i
lion
(\oai:i ..
I.OAKI..
I.C50)
(Sex)
i:i»a
1 den ti lied
Effect
Dose or
Concent r;i
(ion
(\oai:i ..
I.OAKI..
I.C 50)
(Sex)
KITect Measured
Reference
I);itii
Qiiiililv
E\ iiliiiition
Growth
and
develop
ment
Developmental
Sprague-
Dawley,
Female
(25)
75. 237 and 75"
niij kg-bw/da\
Days 6-15
of
geslarion
\o\i:i.
237
mg/kg-
bw/day
Dec leased number of
live I'eLuses per dam and
increased percentage of
resorption sites and
skeletal abnormalities as
well as maternal toxicity
indicated by reduced
body weight gain at the
highest dose;
Becci et al
(1982.)
Medium
971
972
Page 451 of 487
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973
974
975
976
T;ir»el
()r»;ui/
System
Sluilv
Typo
Species, Sli itin,
Sex (Nil in her/
»roup)
Doses/
('oncenlnilions
Diinilion
Author
Reported
KITect
Dose or
Con ccnlni
lion
(\OAKI.,
LOAIX.
IX 50)
(Sex)
i:i»a
1 dent i lied
I! fleet
Dose or
Concenlni
(ion
(NOAKI..
I.OAKI.,
I.C50)
(Sex)
KITecl Me:isiireil
Reference
Qunlilv
K\ nliiiition
Body
Weight
Chronic
(>90 days)
Rat, Ci'i
CD(SD), iioili
(120)
i). 41. 4<)5 niij in
decreased
in 405 mg/m3 males (but
only 6% lower than
controls). Effects on
mortality, hematology
and clinical chemistry
parameters, the kidney,
and cancer incidence
were not temporally-
and/or concentration-
related, and/or were not
toxicologically relevant
(e.g., decreased cancer
incidence).
DuPont
(1982)
Medium
Page 452 of 487
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H.1.5 Hazard and Data Evaluation Summary for Sub-chronic and Chronic Non-cancer Inhalation Exposure Studies
Table Apx H-5. Hazard and Data Evaluation Summary for Sub-chronic and Chronic Non-cancer Inhalation Exposure
Studies
-------
PEER REVIEW DRAFT, DO NOT CITE OR QUOTE
T;ir»et
()r»iin/
System
Study
Type
Species, Si rsiin.
Sex (Nil in her/
"roup)
Doses/
Conccntmlions
Diimlion
Author
Reported
I! lied
Dose or
Concentm
tion
(\OAKI.,
l,()AKI.,
LC 50)
(Sex)
i:i\\
1 denti Tied
Kliect
Dose or
Concentm
tion
(\oai:l.
LOAM..
IX 50)
(Sex)
LITect Mensu red
Reference
D;it:i
Quality
K\:ilu;ition
Clinical
Chem-
istry/
Biochem-
ical
Chronic
(>90 days)
Rat, Cij:
CD(SD), Both
(120)
0, 41, 405 mg/m3
6 hours
da\ 5
days week
\ol
Reported
\OAEL =
4< >5 uiij in'
Body w eight w as
significantly decreased
in 405 mg/m3 males (but
only 6% lower than
controls). Effects on
mortality, hematology
and clinical chemistry
parameters, the kidney,
and cancer incidence
were not temporally -
and/or concentration-
related, and/or were not
toxicologically relevant
(e.g., decreased cancer
incidence).
DuPont
(1982)
Medium
Page 453 of 487
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T;ir»et
()r»iin/
System
Study
Type
Species, Si rsiin.
Sex (Nil in her/
"roup)
Doses/
Conccntmlions
Diimlion
Author
Reported
I! lied
Dose or
Concentm
tion
(\OAKI.,
l,()AKI.,
LC 50)
(Sex)
i:i\\
1 denti Tied
Kliect
Dose or
Concentm
tion
(\oai:l.
LOAM..
IX 50)
(Sex)
LITect Mensu red
Reference
D;it:i
Quality
K\:ilu;ition
Hemato-
logical
and
Immune
Chronic
(>90 days)
Rat, Cij:
CD(SD), Both
(120)
0, 41, 405 mg/m3
6 hours
da\ 5
days week
\ol
Reported
\OAEL =
4< >5 uiij in'
Body w eight w as
significantly decreased
in 405 mg/m3 males (but
only 6% lower than
controls). Effects on
mortality, hematology
and clinical chemistry
parameters, the kidney,
and cancer incidence
were not temporally -
and/or concentration-
related, and/or were not
toxicologically relevant
(e.g., decreased cancer
incidence).
DuPont
(1982)
Medium
Page 454 of 487
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T;ir»et
()r»iin/
System
Study
Type
Species, Si rsiin.
Sex (Nil in her/
"roup)
Doses/
Conccntmlions
Diimlion
Author
Reported
I! lied
Dose or
Concentm
tion
(\OAKI.,
l,()AKI.,
LC 50)
(Sex)
i:i\\
Identified
K fleet
Dose or
Concentm
tion
(\oai:l.
LOAM..
IX 50)
(Sex)
LITect Mensu red
Reference
D;it:i
Quality
K\:ilu;ition
Mortality
Chronic
(>90 days)
Rat, Cij:
CD(SD), Both
(120)
0, 41, 405 mg/m3
6 hours
da\ 5
days week
\ol
Reported
\OAEL =
4< >5 uiij in'
Body w eight w as
significantly decreased
in 405 mg/m3 males (but
only 6% lower than
controls). Effects on
mortality, hematology
and clinical chemistry
parameters, the kidney,
and cancer incidence
were not temporally -
and/or concentration-
related, and/or were not
toxicologically relevant
(e.g., decreased cancer
incidence).
DuPont
(1982)
Medium
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T;ir»et
()r»iin/
System
Study
Type
Species, Si rsiin.
Sex (Nil in her/
"roup)
Doses/
C'oncenlmlions
Diimlion
Author
Reported
I! lied
Dose or
(oiiccntm
tion
(\OAKI.,
l,()AKI.,
LC 50)
(Sex)
i:i\\
Identified
K fleet
Dose or
Coiicen I m
tion
(\oai:l.
LOAKL.
IX 50)
(Sex)
KITect Mensu red
Reference
D;it:i
Qii;ility
Kxidiiiition
Not
Reported
Chronic
(>90 days)
Rat, Cij:
CD(SD), Both
(120)
0, 41, 405 mg/m3
6 hours
da\ 5
days week
\ol
Reported
\OAEL =
4< >5 uiij in'
Body w eight w as
significantly decreased
in 405 mg/m3 males (but
only 6% lower than
controls). Effects on
mortality, hematology
and clinical chemistry
parameters, the kidney,
and cancer incidence
were not temporally-
and/or concentration-
related, and/or were not
toxicologically relevant
(e.g., decreased cancer
incidence).
DuPont
(1982)
Medium
977
978
979
980
981
982
983
984
985
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986 H.1.6 Hazard and Data Evaluation Summary for Sub-chronic and Chronic Non-cancer Oral Exposure Studies
987
988 Table Apx H-6. Hazard and Data Evaluation Summary for Sub-chronic and Chronic Non-cancer Oral Exposure Studies
989
T:ir»et Or»:in/
System
Sluilv
Typo
Species, Sti itin,
Sex (Nilmher/
»roup)
Doses/
('onccntnilions
Diimlion
Author
Reported
K fleet Dose
or (one.
(\OAEI..
I.OAKI..
I-Cs.)
i:i»a
Identified
Kliect Dose
or Cone.
(\()ai:i„
i.OAi:i„
1X5..)
Kl'fect Measured
Reference
l):il:i
Qiiiililv
K\ ;< In :it ion
Body Weight
Sub-
chronic
(30-90
days)
Mouse, Both
(20/sex)
0, 277,619,
1931 mg/kg-
bw/day (0, 1000,
2500, 7500 ppm)
90 JilN s
Not
Reported
\o\i:i. =
N3I nig kg
- h\\ da\
No adverse effects.
Malley et al
(1999)
High
Body Weight
Sub-
chronic
(30-90
days)
Rat, Other, Male
(20-26)
1, 169, 433,
1057 mg/kg-
bw/day (0. 3oihi.
7^0(1 IS nod
ppm)
90 da\ s
\o\i:i.
0.04S
\o\i:i.
1057 mg kg
- bw/day
Body weight effects not
considered adverse
(associated with decreased
food consumption, indicating
palatability issue)
Malley et al
(1999)
High
Body Weight
Sub-
chronic
(30-90
days)
Rat, Other,
Female (2o-26)
i). 217. 5fo.
1344 nig kg-
bw/day (0 JilN s
NOAEL =
0.048
NOAEL =
1344 mg/kg
- bw/day
Body weight effects within
10% of control
Malley et al
High
Body Weight
Chronic
(>90 days)
Ral, Oilier. Male
("2)
0, 6h 4. 2o7. h7X
mg/kg-bw da\
(o. 160o. 5o00,
I5,00o ppm)
2 years
NOAEL =
207 mg/kg -
bw/day
NOAEL =
207 mg/kg -
bw/day
Study authors report a study
NOAEL of 207 mg/kg/day in
male rats based on 25%
decrease in terminal body
weight and increased
incidence of severe chronic
progressive nephropathy.
Malley et al
(2001)
High
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T:ir»el ()r»:in/
System
Sliuly
Typo
Species, Sli itin,
Sex (Nilmher/
»roup)
Doses/
Conccnlnilions
Duration
Author
Reported
Effect Dose
or Cone.
(\()ai:i..
LOAEI.,
I-Cs.)
EPA
Identified
Effect Dose
or Cone.
(\oai:i ..
LOAEI..
IX5..)
Effect Measured
Reference
D:it;i
Qiiiility
E\;ilii;ilion
Body Weight
Chronic
(>90 days)
Rat, Other,
Female (62)
0, 87.8, 283,939
mg/kg-bw/day
(0, 1600, 5000,
15,000 ppm)
2 years
\() All. =
2X3 mg kg -
bw da\
NOAEL =
283 mg/kg -
bw/dav
Stud> aulInn s report a study
NOALI. ol'2S3 mg/kg/day in
female rats Ixised on 35%
decrease in terminal body
weight.
Malley et al
(2001)
High
Body Weight
Chronic
(>90 days)
Mouse, B6C3F1,
Male (50)
0, 89, 173, 1089
mg/kg-bw/day
(0, 600, 1200,
7200 ppm)
18 months
Not
Reported
NJO All. =
1089 mg kg
- bw/da\
No adverse effects
Malley et al
(2001)
High
Body Weight
Chronic
(>90 days)
Mouse, B6C3F1,
Female (50)
0, 115,221,
131^ nig kg-
b\\ 'da\ (i). Mio.
12<)<). 72<>0 ppm)
18 monlhs
Not
Reported
\o.\i:i. =
13 w mg kg
- bw/day
No adverse effects
Malley et al
(2001)
High
Hematological
and Immune
Sub-
chronic
(30-90
days)
Dog. Beagle
Both (6/sex)
(), 24. 75. 24ft
mg/kg-hu da\ in
males. <). 24. 1(\
24() nig/kg-
bw/da\ in
females
13 weeks
Not
Reported
NOAEL =
246 mg/kg -
bw/day
No effects on reproductive
organs,
hematological/immune ,
body weight, relative organ
(liver, kidney, spleen, heart,
thyroid, adrenal glands,
brain, and pituitary) weights.
Becci et al
(1983)
High
Hepatic
Sub-
chronic
(30-90
days)
Rat, Oilier. Male
(10)
1, ]w. 433.
1057 nig kg-
bw/day ((>. 3000,
75IKI. I X.uOO
ppm)
90 days
Not
Reported
NOAEL =
1057 mg/kg
- bw/day
No adverse effects.
Malley et al
(1999)
High
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T:ir»el ()r»:in/
System
Sliuly
Typo
Species, Sli itin,
Sex (Nilmher/
»roup)
Doses/
Conccnlnilions
Duration
Author
Reported
Effect Dose
or Cone.
(\OAEI.,
LOAEL,
LCa.)
EPA
Identified
Effect Dose
or Cone.
(\oai:i ..
LOAEL.
IX5..)
Effect Measured
Reference
D:i(;i
Qiiiility
L\;dii;ilion
Hepatic
Sub-
chronic
(30-90
days)
Rat, Other,
Female (20-26)
0,217,565,
1344 mg/kg -
bw/day (0, 3000,
7500, 18,000
ppm)
90 days
Not
Reported
NOAEL =
1344 mg/kg
- ln\ day
No adverse effects.
Malley et al
(1999)
High
Hepatic
Sub-
chronic
(30-90
days)
Mouse, Both
(20/sex)
0, 277,619,
1931 mg/kg-
bw/day (0, 1000,
2500, 7500 ppm)
90 da\ s
Nol
Reported
\o\i:i,=
1l>31 mg kg
- bw/da\
No adverse effects.
Malley et al
(1999)
High
Hepatic
Chronic
(>90 days)
Rat, Other, Male
(62)
i). <•><•> 4. 2<)7. ^7X
nig kg-I'm da\
(0. | Nil). 5(1(1(1.
15. ppm)
2 \ ears
Not
Reporled
NOAEL =
207 mg/kg -
bw/day
Biliateral
degeneration/atrophy of
seminiferous tubules in the
tests, bilateral
oligospermia/germ cell
debris in the epididymites,
centrilobular fatty change in
the liver
Malley et al
(2001)
High
Hepatic
Chronic
(>90 days)
Ral. Oilier.
I'emale (^2)
o. X7 X. 2X3. <¦)?•<¦)
nig kg-I'm day
(0. | hi in. 5(i()0.
15.(i(Ki ppm)
2 \ ears
Not
Reported
NOAEL =
939 mg/kg -
bw/day
No exposure-related adverse
effects
Malley et al
(2001)
High
Page 459 of 487
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T:ir»ct Or»:in/
System
Sliuly
Typo
Species, Sli itin,
Sex (Nilmher/
»roup)
Doses/
Conccnlnilions
Diimlion
Author
Reported
Effect Dose
or Cone.
(Noael.
LOAEL,
LCa.)
EPA
Identified
Effect Dose
or Cone.
(NOAEL,
LOAEL.
LC«„)
Effect Measured
Reference
D:i(;i
Qiiiility
E\;tliiitlion
Hepatic
Chronic
(>90 days)
Mouse, B6C3F1,
Female (50)
0, 115,221,
1399 mg/kg -
bw/day (0, 600,
1200, 7200 ppm)
18 months
NOAEL =
221 mg/kg -
bw/day
NOAEL=
22 1 mg/kg -
b\\ day
Study authors reported a
study NO ALL of221
mg/kg/dav for female mice
based on increased liver
weight, increased incidence
of hepatocellular basophilic
foci, eosinophilic foci, and
cellular alterations in liver,
and increased hepatocellular
adenoma and carcinoma.
Malley et al
(2001)
High
Hepatic
Chronic
(>90 days)
Mouse. I}^( 31 1.
Male (50)
i). 8l>. 1 73. |t)Xl>
niij kg-hw da\
((). Mil). |2(i(i.
72()() ppm)
1S months
NOAEL=
89 mg/kg -
bw/day
NOAEL =
89 mg/kg -
bw/day
Study authors report a study
NOAEL of 89 mg/kg/day in
male mice based on
increased liver weight in the
mid- and high-dose groups.
At the high dose, additional
effects included increased
incidence of hepatocellular
hypertrophy, clear cell foci,
eosinophilic foci, and
cellular alterations in the
liver.
Malley et al
(2001)
High
Mortality
Sub-
chronic
(30-90
days)
Rat, Other, Male
(10)
1, W>. 433,
1057 niij kg-
h\\ 'day (0. 3000,
7500. 18.000
ppm)
90 days
Not
Reported
NOAEL =
1057 mg/kg
- bw/day
No adverse effects.
Malley et al
(1999)
High
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PEER REVIEW DRAFT, DO NOT CITE OR QUOTE
T:ir»el ()r»:in/
System
Sliuly
Typo
Species, Sli itin,
Sex (Nilmher/
»roup)
Doses/
Conccnlnilions
Diimlion
Author
Reported
Effect Dose
or Cone.
(\OAEI.,
LOAEL,
I-Cs.)
EPA
Identified
Effect Dose
or Cone.
(\oai:i ..
LOAEL.
IX5..)
Effect Measured
Reference
l):t(it
Qiiiility
E\;dii;ilion
Mortality
Sub-
chronic
(30-90
days)
Rat, Other,
Female (20-26)
0,217,565,
1344 mg/kg -
bw/day (0, 3000,
7500, 18,000
ppm)
90 days
Not
Reported
NOAEL =
1344 mg/kg
- hw day
No adverse effects.
Malley et al
(1999)
High
Mortality
Sub-
chronic
(30-90
days)
Mouse, Both
(20/sex)
0, 277,619,
1931 mg/kg-
bw/day (0, 1000,
2500, 7500 ppm)
90 da\ s
Not
Reported
\o.\i:i,=
11>31 mg kg
- bw/da\
No adverse effects.
Malley et al
(1999)
High
Mortality
Chronic
(>90 days)
Rat, Other, Male
(62)
0, 66.4, 207, 678
mg/kg-bw da\
(0. 1600.5
15.000 ppm)
2 years
\() All.
0.048
\() All. =
00 4 mg kg
- bw/day
Decreased survival at 207
mg/kg/day (21%) compared
with control (32%)
Malley et al
(2001)
High
Mortality
Chronic
(>90 days)
Rat, Other,
Female (02)
(). 87 8. 283.
mg kg-hw da\
(0. loud.
15.0(1(1 ppm)
2 \ ears
Not
Reported
NOAEL =
939 mg/kg -
bw/day
No exposure-related adverse
effects
Malley et al
(2001)
High
Mortality
Chronic
(>90 days)
Mouse. B0C311,
Male (50)
d. XW. 173. Idsw
mg kg-hw da\
(o. olio. i:uu.
72UU ppm)
18 months
Not
Reported
NOAEL =
1089 mg/kg
- bw/day
No adverse effects
Malley et al
("2001)
High
Mortality
Chronic
(>90 days)
Mouse, B6( 311.
Female (50)
d, 115. ::i,
1399 mg kg-
hw/day (0. 600,
12d(i. 7200 ppm)
18 months
Not
Reported
NOAEL =
1399 mg/kg
- bw/day
No adverse effects
Malley et al
(2001)
High
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T:ir»el ()r»:in/
System
Sliuly
Typo
Species, Sli itin,
Sex (Nilmher/
»roup)
Doses/
Conccnlnilions
Duration
Author
Reported
Effect Dose
or Cone.
(\()ai:i..
EOAEE,
I-Cs.)
EPA
Identified
Effect Dose
or Cone.
(NOAEL.
EOAEE,
IX5..)
Effect Measured
Reference
l)iit;i
Qiiiility
E\;ilii;ilion
Renal
Sub-
chronic
(30-90
days)
Rat, Other, Male
(10)
1, 169, 433,
1057 mg/kg-
bw/day (0, 3000,
7500, 18,000
ppm)
90 days
Not
Reported
NOAEL =
1057 mg/kg
- h\\ day
No adverse effects.
Malley et al
(1999)
High
Renal
Sub-
chronic
(30-90
days)
Rat, Other,
Female (20-26)
0,217,565,
1344 mg/kg -
bw/day (0, 3000,
7500, 18,000
ppm)
90 da\ s
Not
Reported
noaei.
1344 mg kg
- bw/da\
No adverse effects.
Malley et al
(1999)
High
Renal
Sub-
chronic
(30-90
days)
Mouse, Both
(20/sex)
<). 277. <•> 19.
N3I mg kg-
liw da\ (i).
251)1). 751)1) ppm)
l>o days
Not
Reported
NOAEL=
1931 mg/kg
- bw/day
No adverse effects.
Malley et al
(1999)
High
Renal
Chronic
(>90 days)
Ril. Oilier. Male
CO
o. (•>(•< 4. 2o7. o7S
iiil: kg-bw da\
(0. IW10.
15. ppm)
2 \ ears
\OAEL =
207 mg/kg -
bw/day
NOAEL =
207 mg/kg -
bw/day
Study authors report a study
NOAEL of 207 mg/kg/day in
male rats based on 25%
decrease in terminal body
weight and increased
incidence of severe chronic
progressive nephropathy.
Malley et al
(2001)
High
Renal
Chronic
(>90 days)
Rat, Other
Female (02)
0. 87.8, 283. 939
mg/kg-hu (.lay
(o. 1600. 5000,
15.000 ppm)
2 years
Not
Reported
NOAEL =
939 mg/kg -
bw/day
No exposure-related adverse
effects
Malley et al
(2001)
High
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T:ir»ct ()r»:in/
System
Sliuly
Typo
Species, Sli itin,
Sex (Nilmher/
»roup)
Doses/
Conccnlnilions
Duration
Author
Reported
I! fleet Dose
or Cone.
(\()ai:i..
LOAKI..
I-Cs.)
i:i\\
Identified
KITcct Dose
or Cone.
(NOAEI..
LOAKI..
IX5..)
Kfleet Measured
Reference
l)iit;i
Qiiiility
K\;tluitlion
Renal
Chronic
(>90 days)
Mouse, B6C3F1
- Male (50)
0, 89, 173, 1089
mg/kg-bw/day
(0, 600, 1200,
7200 ppm)
18 months
Not
Reported
NOAEL =
11 >89 mg/kg
- liw day
No ad\ erse el'lects
Malley et al
(2001)
High
Renal
Chronic
(>90 days)
Mouse, B6C3F1
- Female (50)
0, 115,221,
1399 mg/kg-
bw/day (0, 600,
1200, 7200 ppm)
] 8 months
\ot
Reported
\o\rL =
I3w mg/kg
- liw da\
No adverse effects
Malley et al
(2001)
High
990
991
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992 H.1.7 Hazard and Data Evaluation Summary for Cancer Studies
993
994 Table Apx H-7. Summary of Tumor Incidence Data from Animal Cancer Bioassays
995
Species/ Sirsiin/
Diilii
Sex
Kxposure
Doses/
C'iincer
Qiiiilitv
(Niiinher/^roiip)
Route
(oncentmlions
Dumlion
Incidence
I! I'l'ec I
Reference
K\ iiliiiilion
Increased |nluiiai\
Rat/Cij: CD(SD)/
Both (120)
Inhalation,
whole body
0, 41, 405 mg/m3
6 hours/day
5 days/week
for 2 years
Dala nol
invsenled
adenocarcinomas at 41
hul not 405 mg/m' and
at 18 but not 24
months
DuPont
(1982.)a
Medium
(1.8)
0, 87.8, 283,939
Rat/Other/
Female (62)
mg/kg-bw/day (0,
1600, 5000, 15,000
ppm)
2 \ ears
o. 2. 3. 3
Al Icasl one mammary
neoplasm
Increased incidence of
0. 80. 173. |()80
5. 2. 4, 12
hepatocellular
Mouse/B6C3F1/
mgku-hu da\ (ii.
adenoma
Male (50)
Oral,
dietary
60(1. 12(1(1. 720(1
ppm)
4. 1.3, 13 c
Increased incidence of
hepatocellular
carcinoma
Malley et al.
(2001 )b
High (1.2)
18 months
Increased
Mouse/B6C3Fl/
Female (50)
(i. 1 15. 221. I3w
mg/kg-hu da\ ((>.
600, 12(Ki. 72(i(i
ppm)
2, 2, 1,7°
hepatocellular
adenoma and
carcinoma
0, 0, 0, 3 c
Increased
hepatocellular
carcinoma
996 a This is the unpublished study of the published study identified as Lee et al. (198 ?)
997 b Unpublished study of the results in rats is available as NMP Producers Group (1997)
998 c P < 0.05 by Cochran-Armitage trend test
Page 464 of 487
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999
1000
1001
1002
1003
1004
1005
1006
1007
1008
1009
1010
1011
1012
1013
1014
1015
1016
1017
1018
1019
1020
1021
1022
1023
1024
1025
1026
1027
1028
1029
1030
1031
1032
1033
1034
1035
1036
1037
1038
1039
1040
1041
1042
1043
1044
PEER REVIEW DRAFT, DO NOT CITE OR QUOTE
Appendix I PBPK MODELING
The PBPK models of (Poet et at...: ) for describing the toxicokinetics of NMP in rats and humans
were revised for use in deriving an occupational exposure limit (OEL). These PBPK models were
initially evaluated and revised by EPA in 2013 (U.S. EPA. 2013c). Further modifications and calibration
were conducted by Dr. Torka Poet in 2014 (personal communication). In this update, additional data
were considered to further calibrate and validate the model. Model calibration consists of using data to
optimize parameters when those parameters are unknown or approximated, validation is used to show
the fits of the model to other datasets. EPA then evaluated the version submitted by Dr. Poet in 2014 and
made some additional corrections and modifications as described below.
These PBPK models simulate the pharmacokinetics of NMP and its metabolile 51 l-NMP in rats and
humans, described briefly below. The models consist of nine main compartments lung. richly perfused
tissues, slowly perfused tissues, skin, fat, mammary, placenta, fetus and liver for NMP with a submodel
for 5H-NMP. The model can simulate NMP exposures \ ia the oral, inhalation and dermal routes.
Dermal absorption occurs for contact with NMP liquid and vapor. Distribution of NMP to tissues is
assumed to be flow-limited. The model includes mathematical descriptions of the growth of fetal and
maternal tissues during gestation based on a previous PBPK model of pregnancy (Gentry et aL 2002).
Due to extensive differences between rat and human gestation periods, separate rat and human models
were developed. NMP metabolism was assumed to occur in the li\ er NMP was assumed to be
eliminated in exhaled air and urine. 5H-NMP was assumed to be eliminated by further metabolism and
in urine. The physiological parameter values used in the model were obtained from the literature (Gentry
et aL. 2002; Brown et aL. 1997) and biochemical constants for absorption, metabolism and elimination
were fit to the available toxicokinetic data (Fv-_ ,-r- psy-i. ... . i, ;.sk> gv-ulsson. 1997: NMP
Producers Group. 1995a; Midi . . . ?92; Wells and Dige >). Further description of the
PBPK model are available i n ( ) ( ) and the modifications described
below.
1.1 Rat Model
Se\ ei ill col l ections were made to the model code (.csl file) and supporting scripts (.m) files as received
from l)r Torka Poet (personal communication). The first few of these are general and described here.
Blood Flows
Since the placenta is a separate compartment for the 5-HNMP model, its blood-flow and volume were
subtracted from the sums used lor the 'rest of body' for 5-HNMP. Also, the term for blood flow from
the placenta was added to the mixed-venous blood mass balance for 5-HNMP.
To assure flow mass balance, instead of calculating cardiac output (QC) as an initial amount plus the
change from initial for each compartment, it was just calculated as the sum over all the compartments:
Equation 1-1 Cardiac Output
! QC = QCINIT + (QFAT - QFATI) + (QMAM - QMAMI) + QPLA+ (QUTR - QUTRI)
QC = QFAT+QLIV+QSLW+QRAP+QSKN+QMAM+QPLA+QUTR ! pms, 8-13-13
Page 465 of 487
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1045
1046
1047
1048
1049
1050
1051
1052
1053
1054
1055
1056
1057
1058
1059
1060
1061
1062
1063
1064
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Parameter Consolidation
In the provided files, some physiological and chemical-specific parameter were set in separate scripts;
e.g., skin transport parameters in the dermal exposure scripts. This approach creates the potential for
inconsistent parameters between different exposure simulations. Therefore, most parameters are now set
in the ratparam.m script except those which are experimental control variables (e.g., air concentration,
duration of exposure) and pregnancy-specific parameters set in preg_rat_params.m. The final set of
parameters used and any inconsistencies with previous values in ratparam.m that may have differed are
noted in that script.
Recalibration (performed by T. Poet)
Additional data were used to calibrate and validate the intravenous, oral and dermal routes of exposure
in rats. While plasma and urinary excretion data for major metabolite (5-HTnA 11*) ha\ e also been
reevaluated, primary attention has been paid to NMP, since the dose measure of i nleresl are for the
parent chemical. Model parameters for rats are set in the preg_rat_params.m and ratparam m code
scripts (preg_rat_params first calls ratparam), included in the acslX code package availahle with this
assessment. Specific data and modeling choices for the nil are as follow s
Intravenous Data
All available intravenous data were obtained from studies thai administered radiolabeled NMP. Most of
the available studies only provided peak measured concentration and pharmacokinetic parameters. The
study chosen to calibrate the model was that described by ...... .'j., in which nulliparous rats
were exposed to NMP doses ranging from 0.1 to 50<) mg kg I low e\ er, the authors only reported plasma
NMP data for the lowest dose. This time-course data set was used to optimize metabolic rate parameters
(VmaxC and Km) to describe the clearance of NMP from plasma. Unchanged NMP has only been found
at very low levels in rat urine, so urinary elimination was set at a nominal value using a BW-scaled
constant of KLNC= 0.0001 kg0.25 h KLN = KLNC/(BW0.25) = 0.00014 h-1 for a 0.25-kg rat.
Pavan et estimated the post-distribution metabolic rates of NMP from the disappearance of
NMP from plasma in their studies These estimated rates (Km=200 mg/L and VmaxC=1.5
mg/hr/kgi) 75) were used as the seed \ allies for the optimization carried out using the optimization
routines supplied in acslX (v 3 <).2.1; The AEgis Technologies Group, Inc, Huntsville, AL) in which the
model was created. By starting with these values, it was hoped that the dose-range in that study would
be represented and the optimized model would fit across doses. The final optimized parameters were
Km= 225 mg/1 and VmaxC=9 mg/hr/kg0 75. Wells (1988) administered an intravenous dose of 45 mg/kg
to rats, which is 45<)\ higher than the dose used for optimization and this was used to validate the
metabolic rates o\ er a large range (Figure Apx 1-1).
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45 mg/kg simulation
¦ Wells & Digenis (1988)
0.1 mg/kg simulation
Q Payan et al. (2002)
-O
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0.01
0
2
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12
4
Time (h)
FigureApx 1-1. Model Fits to IV Injection Data in Rats
Oral Data
All available oral exposure data were obtained from studies that administered radiolabeled NMP. The
most valuable data sets are those that specifically measured NMP in blood (dose measure used in the
assessment). NMP is highly metabolized and generally not found in urine as unchanged NMP. The study
chosen to calibrate the oral absorption rate was described by Midglev et al. (1992). In this study, male
and female rats received an oral gavage of 105 mg/kg (22.5 mg in rats weighing 192-239 g) NMP, co-
exposed with 2-pyrrolidinone in a water vehicle. The authors concluded that 94.5% of the administered
radiolabel was absorbed. However, when a constant (FRACOR) was fit to the data using the PBPK
model the optimal value was found to be 93%.
The data indicate a rapid uptake and a slow elimination of NMP from plasma. Using the metabolic rate
constants optimized to fit the intravenous dosing and the oral bioavailability measurements of Midglev
et al. (1992). the model estimates of plasma NMP clearance resulted in a much higher AUC than the
data indicated (Figure_Apx 1-2). There is no suggestion of extra-hepatic (i.e.. intestinal) metabolism, so
another mechanism to describe this absorption pattern was investigated. NMP is readily absorbed across
membranes (see dermal absorption data discussion below) and for some chemicals absorption has been
proposed to occur either in the stomach or quickly in the intestine, then more slowly during later phases
of transport ( rimchalk et al.. 2002; Levitt et al. 1997; Staats et al.. 1991). Therefore the original PBPK
model was altered to include primary (stomach) and secondary (intestine) GI compartments to describe
oral absorption following the description from Staats (1991). The resulting model predictions are vastly
improved (Figure_Apx 1-2). Using dual oral absorption results in -75% of the absorbed dose (after
multiplying by 93% bioavailability) being absorbed via the faster process and the remaining -25% being
more slowly absorbed. Also, an unusually high fraction of the radioactivity was found in the feed
residue for the females in the NMP Producers Group (1995a) study, 4.5%, so the simulated dose for that
group was decreased proportionately.
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— 112 mg/kg simulation
¦ Midgley 112 mg/kg data
50 mg/kg (male) simulation
~ Ghantous 50 mg/kg male data
50 mg/kg (female) simulation
A Ghantous 50 mg/kg female data
0 2 4 6 8 10 12 14
Time (hr)
9
8
7
5
4
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i_
— 112 mg/kg simulation
50 mg/kg (female) simulation
¦ Midgley 112 mg/kg data
7 Ghantous 50 mg/kg female data
2
1
0
0
20
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60
80
100
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Time (hr)
FigureApx 1-2. Model Fits to Rat Oral PK Data
Dermal Model & Data
Corrections to the mass balance equations for the rat skin are as indicated in the commented code copied
below. RASK is the rate of changes in the skin compartment. The equation for the amount in the
compartment, ASK, includes the initial condition, ASK0, for the initial dermal application, but
otherwise the correction to RASK makes it the standard format for PBPK models. As received the code
had multiplied CSK rather than CSKV (skin venous blood concentration) by the blood flow (QSKN) for
the rate of efflux in blood and had not separately calculated CSKV.
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Equation 1-2 Rat Skin Model Equations
RASK = QSKN*(CA - CSKV) + RADL ! NOW MINUS CSKV, NOT CSK; PMS 8-21-13
ASK = INTEG(RASK,ASKO) ! Initial value, ASKO, added for Becet et £ 2)
! exposures; pms 8-14-13
CSK = ASK/VSK !'NMP IN SKIN, MG/L'
CSKV = CSK/PSKB ! NMP IN VENOUS BLOOD, PMS 8-22-13
The corresponding flow term for transfer from the skin to the mixed venous blood compartment was
also corrected (i.e., to use CVSK instead of CSK).
While these changes to the skin compartment equations initially degraded the Ills to the dermal exposure
considerably, it also appeared that the associated partition coefficients were not consistent with the
measured values reported by Poet et al. (2010). Table 5. They were recalculated as follows:
Equation 1-3 Rat Skin Partition Coefficients
Skin:liquid, PSKL = 0.42: % value as measured for skin saline, vs. 45<)
Skin:blood, PSKB = 0.12: % (skin:saline)/(blood:saline)
Skin:air, PSKA = 55:
% (skin:saline)*(blood:air)/(blood:saline) = (skin:blood):;:(Mood air)
Developmental studies for NMP have been conducted by the dermal route ( cci et al... 1982). In the
original PBPK model publication (Poet e ). the dermal route was assessed using a permeability
coefficient (Kp) of 4.7x 10"3 cm/hr that was approximated from /// vitro studies (Pavan et al.. 2.003). For
the current assessment, the in vivo dermal exposure studies described by Payan (2003) were used to
optimize Kp. In this study, rats were exposed to 200 |il of neat NMP. According to Payan et al., by
24 hrs after dosing, 80% of the NMP applied had penetrated the skin. The Kp value optimized to these
data was estimated to be 4,6/ 10"3 cm hr (I'igureApx 1-3), which is consistent with the range of Kp
values estimated from the /// vnro studies (from 2.0 x 10"3 to 7.7 10~3cm/hr: (Payan et al.. 2002)).
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600
500
Model
O Payan et al. (2003) data
-I
Oi 400
Q.
£ 300
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(U
I 200
JO
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0 4 8 12 16 20 24 28 32
Time (hr)
FigureApx 1-3. Model Fits to Dermal PK Data from Payan et al. (2003) in Rats
Inhalation
No parameters were optimized to simulate the inhalation exposures of female rats to 104 ppm NMP for
6 hr ( IP Producers Group. 1995a). 100% inhalation bioavailability was assumed. These data, like the
oral exposure data from the same source, appear to be more variable than from other studies. The model
fits to the data are shown in Figure_Apx 1-4.
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— 100 ppm (female) simulation
— 100 ppm (male) simulation
• Ghantous (1995) female data
~ Ghantous (1995) male data
50
0
3
6
9
12
15
Time (hr)
FigureApx 1-4. Model Simulations vs. Inhalation PK Data from Ghantous (1995a) for NMP
Inhalation in Rats
Exposure Control for Bioassay Simulations
Because both Becci et al. (1982 and Saillenfait et al. (2002) explicitly stated that the animal BWs were
measured every 3rd day of gestation and the dermal/oral doses were adjusted accordingly on those days
(as BW increases during pregnancy), corresponding conditional (if/then) statements were added to the
'GAVD' and 'REAPPLY' discrete blocks, to re-calculate the doses on those days.
The code for the dermal discrete blocks follows. ASK0 is the total absolute amount applied; DSK is the
dose/kg BW. Because Becci et al. (1982) rubbed the material into the skin, it is assumed to be added
directly into the skin compartment (ASK), rather than as a liquid on top. Hence the dose is given as an
addition of ASK0 (mg/day applied) to ASK.
Equation 1-4 Dermal Dosing Equations
DISCRETE SKWASH ! PMS, 8-14-13
ASK = 0.0 ! Assume skin washing in Becci et al. (1982) removes all NMP IN skin
if (DAYS.LT.15.0) SCHEDULE REAPPLY.AT.(T+DOSElNTERVAL-TWASH)
END
DISCRETE REAPPLY ! PMS, 8-14-13
IF (ROUND(DAYS).EQ.9.0) ASKO=DSK*BW
IF (ROUND(DAYS).EQ. 12.0) ASKO=DSK*BW
IF (ROUND(DAYS).EQ. 15.0) ASKO=DSK*BW
ASK = ASK + ASKO
SCHEDULE SKWASH.AT.(T+TWASH)
END
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Also, because Becci et al. (1982.) washed the skin area exposed to dermal application at the end of a set
time interval, a "SKWASH" discrete block was introduced at which time the amount in that patch of
skin was assumed to be momentarily reduced to zero. During periods of dermal application, transport
from the liquid to the skin was turned on using the pulse function, DZONE. After removal of the liquid
it was assumed that NMP in the skin patch could volatilize into the otherwise clean air, with the rate
defined by the same permeability constants, but using the skin:air partition coefficient.
The rate of transfer to/from the skin area is then defined by:
Equation 1-5 NMP Dermal Transport
RADL=(KPL*SA/1000.0)*((CSURF-(CSK/PSKL))*DZONE - ( I 0-DZO\'r.)*(CSK/PSKA))
! 2ND term, (1.0-DZONE)*(CSK/PSKA), allows for evaporative loss when l)/()NE=0
The primary part of this equation for transfer when liquid is in contact with the skin.
(KPL*SA/1000.0)*(CSURF-(CSK/PSKL)), is identical to that used previously by McDougal (1986).
Finally, a constant, CONCMGS, was introduced so that the air concentration could lx- set directly in
mg/m3. This is converted to the concentration in mg/L (COVCMG) in the code and added lo the
inhalation exposure, turned on and off using the switch. CI/OM-. w Inch is turned on and off using
SCHEDULE/DISCRETE statements:
Equation 1-6 NMP Vapor Exposure Control
CI = CCH*PULSE(0., DOSEINTERVAL, i CI l\(i) ('[ZONE:::CO\C\l(i 'MG/L
! Added CIZONE*CONCMG, PMS, 8-13-13
1.2 Human Model
Human exposures to NMP will be primarily via the inhalation route; contribution from the dermal route
(vapors or liquid) may also be significant if not primary for some scenarios. Ingestion of NMP is not
expected to be a significant pathway in human populations. Both controlled and occupational human
exposure data are a\ ailable from the published I item lure. Controlled human biomonitoring studies were
used to calibrate NMP and 5-HNMP metabolic rates and a workplace exposure assessment study was
used lo \alidalethe model and exposure scenarios.
1.2.1 Corrections lo Human Model Structure
NMP Metabolism and Urinary Elimination
Since the human PK data were consistent with a nearly linear model (first-order kinetics, including
metabolism) estimation of a metabolic saturation constant, Km, using the traditional Michaelis-Menten
equation for metabolism of NMP, was difficult. In particular as estimates of Km became larger, model
fits became less sensitive to variation in its value. Therefore, equation was changed from the standard
form, rate = Vmax*C/(Km + C), where C is the concentration of NMP in the liver, to the equivalent
form, rate = VK1*C/(1 + AF1*C), where VK = Vmax/Km and AF1 = 1/Km. These two forms are
mathematically identical given the relationship between parameters just shown. The affinity constant,
AF1, can be easily bounded to be non-negative and possibly converge to zero, corresponding to an
indeterminately large Km. Since VK represents hepatic metabolism, it was assumed to scale with BW
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the same as Vmax; i.e., VK1 = VK1C*BW0.75. The urinary elimination of NMP was assumed to be
first order, rather than saturable, using a rate constant (KUMNE) that was not scaled by BW.
5-HNMP
Since 5-HNMP is not being considered as an internal metric for toxicity and its volume-of-distribution
(VOD) appeared to be over-estimated using the original PBPK model structure and measured tissue
partition coefficients, its description was replaced with a classical one-compartment PK model. Further,
as the metabolism of 5-HNMP also appeared to be linear and the data for estimating a Km value even
weaker, a transformation of its metabolic rate equation like that for NMP described just above was
assumed, but with the affinity assumed to be effectively zero, resulting in a first-order metabolic rate
equation. As with NMP, the urinary elimination of 5-HNMP was also assumed lo be first-order. The
resulting model then becomes:
Equation 1-7 5-HNMP Metabolism and Elimination
d A5H/dt = RAMET1 *STOCH - RAMETM 1 - RATI ll>
(rate of change of amount of 5-HNMP)
CVEN1 = A5H/VOD5H (concentration of 5-HNMP in venous blood)
VOD5H = VOD5HC*BW (volume of distribution assumed to scale with BW)
RAMETM 1 = -CVEN1 *VK2, where VK2 = VK2C*BW0.75
(rate of metabolism of 5-HNMP)
RAUHP = KME*CVEN1 (rate of urinary elimination of 5-HNMP)
RAMET1 = rate ofNMP metabolism to 5-HWIP (mg NMP metabolized h)
STOCH = ratio of 5-HNMP to NMP molecular weights
Exposure and Timing Control
A table function, RESLVL, was added as a place-holder for reading in defined (consumer) inhalation
exposure time-courses; specifically from EPA exposure assessment modeling.
A constant, GDstart, the day of gestation on which the simulation starts and a variable Gtime, the hrs
into gestation, were added to facilitate separating exposure control from gestation timing.
A second set of D1SCRI-TI- SCI II-1)1 I.I- blocks were added to allow for split exposure scenarios
(morning afternoon worker exposure: dual-episode consumer exposures). DZONE, set in the
DISCRETE SCHEDULE blocks, controls the time within a day when discontinuous exposure occurs.
Czone is the product of DZONI- and a pulse function used to control for days/week exposure in
workplace scenarios
Equation 1-8 Vapor Exposure Scheduling
Czone = pulse(0.0,full\\eek,hrsweek)*DZONE ! pms 8-20-13
! for a 5 day/wk exposure, use fullweek=7*24, hrsweek=5*24 (Dayswk=5)
! for a single day, fullweek=lel6, hrsweek=24 (Dayswk=l)
A binary constant, BRUSH, was added to set exposure scenarios when dermal contact with liquid
occurs. For workplace scenarios, exposure to vapor and liquid are assumed to be simultaneous; i.e., the
worker leaves the location with NMP vapor and washes his/her hands when he/she has finished applying
the material.
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Skin Compartment
The original skin compartment which is coded to include uptake from liquid-dermal contact was
renamed by adding "L" to the end, SK -> SKL and a second skin compartment to account for concurrent
vapor-skin uptake, SKV, was added. This was done because when the human model was calibrated for
inhalation exposure, an exposed skin surface area of 6700 cm2 was used. When this surface is reduced to
~ 0, predicted blood levels of NMP are reduced ~ 45%. Thus vapor uptake through the skin is a
significant component of inhalation exposure and there is no reason to assume, a priori, that this uptake
(or desorption) does not occur through a similar area of exposed skin during workplace and consumer
exposures, except for any area that would have liquid contact or otherwise be occluded (e.g., by
protective equipment). So the SKV compartment allows for simultaneous absorption of vapor-through-
skin that does not have liquid contact and from areas of skin with liquid contact. The surface area of
SKV and SKL are SAV and SAL, respectively. SAL can set directly for different exposure scenarios.
To account for variations with individual BW, a parameter for the fraction of skin area exposed to vapor
was introduced: SAVC, with SAV = SAVC*TSA, where TSA is the total body surface area. TSA is
calculated for each individual based on BW and height. For EPA simulations, SAVC was set lo 0.25,
representing the head, neck, arms and hands, minus any area assumed lo have liquid contact or covered
with protective gloves or a face-mask.
The rate for delivery from a liquid film to the "SKIskin com pari men l (also see further below) is then
defined by:
Equation 1-9 NMP Liquid Rate of Delivery lo Skin
RADL = (PVL*SAL/1000.0)*(CSURF-(CSKI. PSkl.nHzoiurURl SI I
! Net rate of del i\cry lo "I." skin from liquid, when liquid is there
The equations for transfer of \ apor (air concentration = CI) to the SKL compartment, which occurs
during periods with no liquid spray contact lor the SKL compartment are similarly:
Equation T-10 NMP Vapor Rate of Delivery lo Skin
RADVL = (PV*SAI. 11)0() 0)*(CI - 0
AH20 = (DENSITY+1 0-CONCL)*VLIQ0 ! ... and add it to H20. pms 9-16-14
A mass-balance equation was then added to attract the remaining amount and volume on the skin
surface, which is then used to calculate the concentration:
ASURF = INTEG(-RADL, DDN) ! Amount in liquid. DDN is the initial amount.
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VLIQ = (AH20 + ASURF)/DENSITY
CSURF = ASURF/VLIQ
This volume balance is important for analysis and calibration of the dermal PK studies where small
volumes (5 or 10 ml) were applied at the beginning of the exposure and not replenished. However in
workplace and consumer user exposures, it is assumed that fresh liquid is constantly replacing any NMP
that is absorbed, keeping the surface concentration essentially constant. Therefore the initial volume,
VLQ0, is set to a large value (106 L) for those scenarios.
The skin partition coefficients were also recalculated as was done lor the rat. with rat parameters for
skin:saline and blood:air, but human blood:saline.
Tissue and Blood-Flow Mass Balances
The model had been previously coded with an alveolar blood compartment (AI .V). Inn this was
commented out in the DYNAMIC section. Therefore this \ olume fraction should not be subtracted when
calculating the slowly-perfused volume. The fraction of blood-flow to slowly perfused tissue was
updated to also account for the SKV compartment; on the other hand a separate skin compartment is not
used for 5-HNMP, so the skin blood flow is NOT subtracted for the metabolite-slowly-perfused
compartment (SLW5). These have all been corrected.
QSKCC (original fractional flow to the skin) had been subtracted twice, both in calculating QSLWC and
then in the calculation of QSLW. The 2nd subtraction created a mass balance error and hence was
removed. On the other hand, placental blood flow is now subtracted, so the total flow to slowly-perfused
continues to total cardiac output minus all other tissue group flows
For tissues for which the \ olume changes with gestation day, the initial values were corrected to match
the calculation in the DYN AMIC section, which apply at the first time-step. In the dynamic section, the
calculation of QC was corrected to include the "increase* in placental flow (QPLA - QPLAI) rather
than the total placental flow (QIM ,.\). since QCIXTT includes QPLAI. QSLW5 and VSLW5 (5-HNMP
slow compartment flow and volume) are now calculated in the DYNAMIC section by subtraction. The
calculation of QC was otherwise left in its original form, in contrast to the ratPBPK model.
Parameter C onsolidation
Like the rat model, the human model physiological and biochemical parameters are now primarily set in
a single script, human params.m. Initial values for the metabolic and vapor-absorption (KPV)
parameters were obtained by fitting Bader et al. (2006) inhalation data with the exception of the high-
concentration data from one individual, but the data otherwise grouped without distinction between
individuals (further details below). An alternate set of fitted parameters was obtained by fitting the data
for each individual separately, focused on the low-concentration data and then calculating the average of
each parameter across the individually-fitted values. This subset of parameters is selected by using
human_avg_params.m. Since further analysis of the dermal absorption of liquid NMP showed that this
uptake differed between neat (100%) NMP and diluted (50%) NMP, separate value of PVL were
obtained for neat vs. diluted NMP (also see below). Hence only constants which define specific
exposure scenarios (include skin areas exposed) and PVL are defined in the specific simulation scripts.
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Inhalation Data
A study conducted by the Hannover Medical School, University of Dortmund, Germany (Badcr and Van
Thriel. 2006) was used to calibrate inhalation parameters of the model. In this study, 8 healthy, non-
smoking, male volunteers were exposed to 10, 40 or 80 mg/m3 NMP in an environmental chamber. Over
the course of several weeks, each volunteer was exposed sequentially to all 3 concentrations. The 8
volunteers were separated into 2 groups of 4 and each group was exposed in a shared chamber. The
exposures were carried out in ascending concentrations, with a 1-week period between each session.
Volunteers wore slacks and T shirts and thus had arms exposed to vapor. Blood was collected from each
volunteer in the middle of the 6-hr exposure period, at the end of exposure (6 hr) and 1, 2, 3, 18 and 42
hrs after the end of exposure. Urine was also collected from each volunteer at times up to 42 hrs after the
end of exposure. Because it is relatively rare to have blood and urine data for multiple exposure levels,
multiple time points, in individuals, efforts were made to ensure the exposure scenarios for these data
were modeled as accurately as possible.
To collect the mid-exposure blood samples, volunteers left the chamber one at a lime and moved to
another room to have blood drawn and to give a urine sample The data are consistent with a sharp drop
in concentration for the mid-exposure blood sampling, when the peak NMP concentration measured at
the end of the exposures are considered. In the report, the time taken to leave the chamber, walk to the
new room, donate blood and urine was suggested to be about I <> mi nines. However, exact times were not
recorded. The notes indicate that the time between blood collection and urine collection was at least 5
minutes. In addition, the recorded times for col I eel ion of blood from first collected sample to last {i.e.,
between the first and fourth volunteers to lea\ e the chamber) was up to 55 minutes. If the times were
equivalent for each subject and the volunteers only left the chamber as the previous volunteer returned,
this would indicate an average of 12 minutes was needed lor sample collection from each volunteer.
Based on a careful review of the data tables in Bader and van Thriel (2006) and personal communication
with Dr. Michael Bader and Dr. Chrisioph van Thriel, it was determined that each subject entered and
left the exposure chamber at different limes as described just above and were likely not sampled at
exactly the same time after the beginning and end of each exposure segment. While the total exposure
time for each subject was monitored and kept lo exactly 6 h on each exposure day, based on the timing
of the blood and urine samples (taken outside the exposure chamber), it is clear that the study design
was not exactly followed. In particular, u liile the morning and afternoon exposures were supposed to be
3 h each, the time between the mid-day and first afternoon blood samples was less than 3 h for some
individuals in some exposures (and the mid-day sample was taken much later after noon for such
samples). In these cases it seemed likely that the individual spent slightly more than 3 h in the chamber
in the morning and slightly less in the afternoon, for that exposure. Based on the recorded data and
communications, the exposure timing used for modeling and simulation was set to 3.1 h for the morning
exposure, a mid-day break of 0.2 h (12 min) and 2.9 h for the afternoon exposure. Since individual
subjects did not enter and exited the chamber at exactly the same time, the time of their entrance to the
chamber for each exposure was estimated based on the recorded times of the blood and urine samples.
The sample times used for modeling were then calculated relative to the estimated entry times.
It was also clear that a number of the measurements, especially those of 5-HNMP for the low-
concentration exposure, were recorded as the limit-of-detection (LOD), when the measured value fell
below this limit. This was confirmed with Dr. Bader (personal communication). Therefore all
measurements at/below the LOD were removed from the data set to avoid the bias they would otherwise
introduce.
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It also appeared that the high-concentration-exposure (80 mg/m3) for one subject deviated substantially
from the other subjects; see FigureApx 1-5 below. Since the blood concentration at 6 h was well below
those of the other subjects and that at 24 h well above (4 subjects had levels below the LOD), this
individual's high concentration set was excluded from analysis of the grouped data. Blood
concentrations at the middle and low exposure for this individual were among the range of the other
subjects, hence included in the group data.
With this one data set removed, the revised model was fit to the group data for exposures at 9.7 and 80
mg/m3, by adjusting the following parameters: PV, VK1C, ATI, KUMNE, VK2C, VOD5HC and KME.
Since the data for the 40 mg/m3 exposure were consistent with the 80 mg/m3, but the data for 9.7 mg/m3
appeared not to be and it was considered especially important to describe low-concentration exposures,
the 40 mg/m3 data were excluded from this exercise. The resulting parameter values are as follows, with
model fits to the group data shown in Figure_Apx 1-6, left side. These fits are compared to ones obtained
by fitting the data for each individual separately, where possible using only the low-concentration
exposure data and then calculating the average across the individual fits for each parameter (right side of
FigureApx 1-6; details below).
0.9
~
n
15 20 25
Time (h)
Figure Apx 1-5. NMP Blood Concentration Data from Bader and van Thriel (2006)
Curves are simulations for 9.7, 40 and 80 mg/m3 exposures. Squares are individual blood concentration
data for the 80 mg/m3 exposure. Solid squares are from the one individual with the highest BW and
height (102 kg, 190 cm), compared to the other subjects (65-80 kg, 168-183 cm).
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2.1
-J
9
1.8
E
1.5
"O
o
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c
a
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0.3
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1.6
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140
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120
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100
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X
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to
20
0
0
Model fit, 80 mg/m3
Model fit, 40 mg/m3
~
~
Modi fit, 9.7 mg/m3
/t)
a Exp obs 80 ppm
/Bp
A Exp obs 40 mg/m3
A
f ^
v Exp obs 9.7 mg/m3
!\
i/]
ii v
'ifk
10 15
Time (hrs)
20
25
10 15
Time (hrs)
s
~ [13
dd dd
a
~
j 1itu °d°jB8 b
"fjg
m v
10
20 30
Time (hrs)
40
50
B
~
0
*Yv-. .
. ^TT"
20 30
Time (hrs)
40
50
Model fit, 80 mg/m3
Model fit, 40 mg/m3
Modi fit, 9.7 mg/m3
Exp obs 80 ppm
Exp obs 40 mg/m3
Exp obs 9.7 mg/m3
10 15
Time (hrs)
10 15
Time (hrs)
n* VflBB 0 oi
JA A a^D^oA %,/&>•
^ « - Vv V
20 30
Time (hrs)
aA a * ^ >,
20 30
Time (hrs)
FigureApx 1-6. Alternate Fits to Collective Data from Bader and van Thriel (2006)
Left panels show fits to the groped data for 9.7 and 80 mg/m3 (data shown). Simulations in right panel
used average of parameters fit to each individual separately, primarily for 9.7 mg/m3 (see text for
details).
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Piinimelers rilled lo "roup d:il;i
lor 9.7 :tnil SO m<>/nr' exposures
A\erii»e of p:ir;iinelers lit to d;il;i lor e;u-h
indix idiiiil sep;ir;ilel\. priniiirilv ().7 in«/iii "
PV =1.6 (cm/h)
VK1C = 0.47 (L/(h*kg0 75))
AF1 = 0.02 (L/mg)
VK2C = 0.035 (L/(h*kg°75))
VOD5HC = 0.26 (L/kg)
KME = 2 .3 (L/h)
KUMNE = 0.092 (L/h)
PV= 16.4 (cm/h)
VK1C = 0.386 (L/(h*kg0 75))
AF1 = 0.02 (L/mg) [fixed at group-fit value]
VK2C = 0.0359 (L/(h*kg°75))
VOD5HC = 0.243 (L/kg)
KME = 2.75 (L/h)
KUMNE = 0.103 (L/h)
In their summary statistics, Bader and van Thriel (2006) reported group-averages of the peak NMP
blood levels as being 0.293 mg/L for the 9.7 mg/m3 and 1.585 mg/m3. The ratio of these two
(1.585/0.293 = 5.4), is considerably less than one would expect assuming linearity with exposure level
(80/9.7 = 8.25) and is the opposite of what one would expect due to metabolic saturation of the
conversion of NMP to 5-HNMP. This is not true for the ratio peak 5-HNMP levels in blood (8.08),
however, which is comparable to the relative exposure level II" the nonlinearity in NMP blood levels
were due to more efficient metabolism at the higher exposure le\ el. then ratio of 5-HNMP blood levels
would have been greater than expected.
Since the mechanism for the nonlinearity in Mood NMP le\ els is unclear and it would be undesirable to
under-estimate NMP blood levels and hence human risks at lower exposure levels, it was decided to
estimate parameters using only the low-exposure data, if possible or with minimal use of the high-
exposure data. (For two of the subjects the blood levels of 5-MN iVIP did not rise above the LOD for the
low exposure, making it impossible to estimate VOD5.HC for them. Hence the 80 mg/m3 blood 5-
HNMP data were also needed to estimate their parameters.) Given the observation that the high-
exposure data for one subject was disparate from the other subjects, it also seemed possible that the
apparent nonlinearity in the average PK data was due to the mixing of data from the 8 subjects in the
study. Therefore fits focused on the low-exposure data were conducted separately for each subject. Since
limiting to the low-exposure data would provide almost no information on metabolic saturation and the
affinity (AF1) obtained from the fits to the group data was quite low (0.02 L/mg), AF1 was held at that
group-fit value for this exercise. The resulting parameter values are listed in Table Apx 1-1 and fits to
the individual data shown in FigureApx 1-7 - FigureApx 1-10. In order to allow one to see the fit to the
low concentration and otherwise compare the fits across individuals, the y-axis scale was held constant
for each analyle across the individuals, though this meant that the simulation curves for the higher
exposure data sometimes went off the top of the plot.
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1492 TableApx 1-1. Estimated PBPK Parameters for Each Subject of the Bader and van Thriel (2006)
1493 Experiments
Subject
YKIC
ki mm:
PV
YK2C
kmi:
VOI)5ll(
1
0.25
0.11
19
0.017
3.2
0.2
4
0.17
0.042
34
0.004
3
0.14
10
0.22
0.069
35
0.027
2.8
0.12
12
0.63
0.046
12
0.044
1.9
0.39
14
0.57
0.2
10
0.08
2.5
0.4
16
0.45
0.06
0
0.08
1 9
0.2
17
0.38
0.2
20
0.02
4 3
0.26
25
0.42
0.1
1.5
0.015
24
0.23
average
0.386
0.103
16.4
0.0359
2.75
0.243
1494
1495 It is interesting to note that for half of the subjects (#12. 14. .. 16 and #25), the Ills and data for NMP in
1496 blood show that the data are quite consistent with the essentially linear PBPK model, u liilc for the other
1497 half the simulations with parameters fitted to the low-concentration data over-predict the liiuh-
1498 concentration NMP data.
1499
1500
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_ 2.1
^ 18
E 1.5
1 1.2
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5 0.9
- 0.6
Q.
£ 0.3
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0
v
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NOT CITE OR QUOTE
2.1
1.8
1.2
5 0.9
- 0.6
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£ 0.3
Model 80 mg/m3
Model 40 mg/m3
Model 9.7 mg/m3
~ Exp obs 80 ppm
A Exp obs 40 mg/m3
V Exp obs 9.7 mg/m3
Model 80 mg/m3
Model 40 mg/m3
Model 9.7 mg/m3
~ Exp obs 80 ppm
A Exp obs 40 mg/m3
V Exp obs 9.7 mg/m3
12 18
Time (h)
24
Time (h)
1.6
1.4
1.2
1
0.8
0.6
0.4
0.2
0
°^A A A
v vw v v
12
24 36
Time (h)
48
Time (h)
Time (h)
n ~ ~ D D
24 36
Time (h)
24 36 48 0 12 24 36
Time (h) Time (h)
Figure Apx 1-7. Model Fits to Subjects 1 and 4 of Bader and van Thriel (2006)
Model fit separately to each subject. See text for details.
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1511
1512
1513
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Model 80 mg/m3
Model 40 mg/m3
Model 9.7 mg/m3
Exp obs 80 ppm
Exp obs 40 mg/m3
Exp obs 9.7 mg/m3
12 18
Time (h)
/
Time (h)
24 36
Time (h)
Model 80 mg/m3
Model 40 mg/m3
Model 9.7 mg/m3
Exp obs 80 ppm
Exp obs 40 mg/m3
Exp obs 9.7 mg/m3
Time (h)
Time (h)
~
~ ~~ ~ ~ nr
A A AJiAA A
—?—9 77
12
24 36
Time (h)
12
24 36
Time (h)
48
~ ~ ~ ~
24 36
Time (h)
Figure Apx 1-8. Model Fits to Subjects 10 and 12 of Bader and van Thriel (2006)
Model fit separately to each subject. See text for details.
48
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1518
1519
1520
1521
1522
0>
_c
L
3
_c
Q.
T
Z
Model 80 mg/m3
Model 40 mg/m3
Model 9.7 mg/m3
Exp obs 80 ppm
Exp obs 40 mg/m3
Exp obs 9.7 mg/m3
12 18
Time (h)
1.6
1.4
1.2
1
0.8
0.6
0.4
0.2
0
12 18
Time (h)
~ ~
AA
VYVV
12
24 36
Time (h)
48
2.1
-1
1.8
u>
E
«w»
1.5
•a
o
1.2
o
CO
0.9
c
0.6
Q.
5"
0.3
Z
0
S
4
3.5
c
E
3
¦o
o
2.5
o
ta
2
c
1.5
a
T
1
Z
0.5
X
m
0
1.6
9
E
1.4
w
1.2
o
C
1
GO
o
_C
0.6
Q.
T
0.4
Z
0.2
0
140
c>
E
120
V
100
C
L.
D
80
C
60
a
5"
40
z
X
20
lO
0
Model 80 mg/m3
Model 40 mg/m3
Model 9.7 mg/m3
~ Exp obs 80 ppm
A Exp obs 40 mg/m3
V Exp obs 9.7 mg/m3
12 18
Time (h)
-PW V v-
12
24 36 48 0 12
Time (h)
Figure Apx 1-9. Model Fits to Subjects 14 and 16 of Bader and
Model fit separately to each subject. See text for details.
24
12 18 24
Time (h)
~ ~ ~ ~
A A A_
24 36 48
Time (h)
u—n—s-
24 36
Time (h)
van Thriel (2006)
48
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Model 80 mg/m3
Model 40 mg/m3
Model 9.7 mg/m3
Exp obs 80 ppm
Exp obs 40 mg/m3
Exp obs 9.7 mg/m3
Model 80 mg/m3
Model 40 mg/m3
Model 9.7 mg/m3
Exp obs 80 ppm
Exp obs 40 mg/m3
Exp obs 9.7 mg/m3
12 18
Time (h)
12
Time (h)
12
Time (h)
Time (h)
cm ~~ ~~
~ AAA
24 36
Time (h)
24 36
Time (h)
WV
24 36 48 0 12 24 36
Time (h) Time (h)
Figure Apx I-10. Model Fits to Subjects 17 and 25 of Bader and van Thriel (2006)
Model fit separately to each subject. See text for details.
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Dermal Data: Vapor and Liquid
Volunteers in the study described by Akesson and Paulsson (1997) wore shorts and t-shirts and thus also
had dermal (vapor) exposures, as well as inhalation exposures, to NMP. The exposure concentrations for
this study were similar to those of Bader et al (2005). With only inhalation exposures, the model under-
predicted plasma NMP by about 25%, a vapor permeability coefficient, which accounts for both the skin
permeability and the vapor/skin surface interaction, (PV) of 1.5 cm/hr was optimized to fit these data
and is equivalent to the previously optimized value (Poet et al.. 2010) (Figure_Apx 1-11).
simulation, with dermal
simulation, with dermal
simulation, with dermal
simulation, no dermal
simulation, no dermal
simulation, no dermal
data
data
data
53 mg/m3
24 mg/m3
10 mg/m3
53 mg/m3
24 mg/m3
10 mg/m3
53 mg/m3
24 mg/m3
10 mg/m3
12 15
Time (hr)
18
21
24
FigureApx 1-11. Model Fits to Human Inhalation Data of Akesson and Paulsson (1997), With and
Without Dermal Absorption of Vapors
Model parameters were as obtained previously using the data of Bader and van Thriel (2006).
Simulations are shown with dermal absorption of vapors included ("with dermal"; 25% of total surface
area assumed exposed) or turned off ("no dermal").
Akesson et al. (2004) exposed 12 volunteers (6 male and 6 female) to 300 mg NMP either neat or
diluted 50:50 in an aqueous solution. Blood and urine 5-HNMP concentrations were monitored for up to
9 days. The plasma 5-HNMP concentration was extracted from the figure using Digitizlt
(Braunschweig, Germany). Urinary 5-HNMP concentrations were extrapolated to total amount
eliminated using the assumption that the average urinary flow for an adult is 18 ml/kg-day ( Teffernari et
al.. 2014). Aqueous dilution resulted in a slower time to reach peak plasma 5-HNMP and a reduction in
peak plasma concentration. Because the urinary elimination constant (KME) for 5-HNMP was seen to
vary among subjects when fitting the Bader and van Thriel (2006) data (see Table HI) and we did not
want a lack-of-fit to the urinary elimination data (which establish the mass balance, hence total amount
absorbed) to adversely impact the fitting of the 5-HNMP blood levels, KME was also fit to each data set
then. Optimized liquid Kp for neat NMP was 2.05 x 10"3 cm/hr (with KME = 4.54L/hr). To fit the data
from the diluted exposures, a lower Kp of 2.87xl0"4 was needed (with KME = 2.10 L/hr) (Figure Apx
1-12). These liquid dermal permeability coefficients were used in estimating human dermal absorption
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for neat and diluted NMP absorption, though with KME kept at the average value from the Bader and
van Thriel (2006) study (2.3 L/hr). (Note that KME does not impact NMP blood levels.)
Workplace Observer Study
In a biomonitoring study Xiaofei (2000) followed 4 workers and 5 observers in a lens manufacturing
facility. The workers washed lenses with NMP, working 11-hr shifts with a 1-hr lunch break (total 12
hrs within the facility). Observers were stated to be in the facility from 8 am to 5 pm for a single day, but
the tabulated exposure metrics indicated only 8 h of exposure, so it was assumed that they also took a 1-
hr break (at noon). The mean exposures for the observers was 0.28 ppm, with a range from 0.24 to 0.32
ppm. The PBPK model underestimated plasma NMP concentrations for the workers (data not shown)
and observer by ~3x when no dermal exposure is assumed (Figure_Apx 1-13). However, droplets of
NMP were noted on the lenses as the workers were moving those lenses to drying racks. Just assuming
that these droplets were due to some aerosolized NMP and that the observers had a small surface area of
skin exposed to such droplets, 0.2 cm2, gave results that better fitted the blood data during the exposure,
but the clearance after exposure appeared to be too rapid. Assuming that the average metabolic rate was
'/2 of that identified from the Bader and van Thriel (2006) data {i.e., VK1C = 0.193 L/h-kg0.75) with an
even smaller exposure to aerosol (0.1 cm2 of exposed skin) resulted in simulations that matched the data
well (Figure_Apx 1-13). The lowest individual VK1C estimated for the Bader and van Thriel (2006) data
was 0.17 L/h-kg0.75, so the value used here is not unreasonable. In summary, the un-adjusted model
gave simulations that were within a factor of three of this data set and the discrepancy can be explained
by a reasonable level of metabolic variability between the two study populations and a small amount of
dermal contact.
Model simulation, men, neat NMP
Model simulation, women, neat NMP
Moodel simulation, men, 50% NMP
Akesson et al 2004 men, neat NMP
Akesson et al 2004 women, neat NMP
Akesson et al 2004 men, 50% NMP
0
5
10 15 20 25 30
Time (h)
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1585
1586
1587
1588
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1590
1591
1592
o>
E
0)
c
'l
D
CL
£
Z
I
I
m
Model simulation, men, neat NMP
Model simulation, women, neat NMP
Moodel simulation, men, 50% NMP
Akesson et al 2004 men, neat NMP
Akesson et al 2004 women, neat NMP
Akesson et al 2004 men, 50% NMP
40
50
60
30
Time (h)
FigureApx 1-12. Model Fits to Human Dermal Exposure Data of Akesson et al. (2004)
0.12
0.1
oi 0-08
E
v—/
CL
£
z
-o
g 0.04
CO
0.02
0.06
0.24 ppm simulation
0.32 ppm simulation
0.28 ppm, modified"
Volunteer A
Volunteer B
Volunteer C
Volunteer D
Volunteer E
18
21
24
0 3 6 9 12 15
Time (hr)
Figure Apx 1-13. Workplace Observer Simulations Representing Subjects of Xioafei et al. (2000)
* Metabolic elimination was reduced to %. that estimated from Bader and van Thriel (2006) data and
0.1 cm2 of skin was assumed exposed to liquid aerosol.
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