v>EPA
United States EPA Document #740-Rl-8013
Environmental Protection Agency August 2020
Office of Chemical Safety and
Pollution Prevention
Risk Evaluation for
1-Bromopropane
(w-Propyl Bromide)
CASRN: 106-94-5
r h
w n
August 2020
-------
TABLE OF CONTENTS
TABLE OF CONTENTS 2
LIST OF TABLES 10
LIST OF APPENDIX TABLES 17
LIST OF FIGURES 17
LIST OF APPENDIX FIGURES 19
LIST OF EQUATIONS 19
LIST OF APPENDIX EQUATIONS 20
ACKNOWLEDGEMENTS 21
ABBREVIATIONS 22
EXECUTIVE SUMMARY 30
1 INTRODUCTION 43
1.1 Physical and Chemical Properties 44
1.2 Uses and Production Volume 46
1.3 Regulatory and Assessment History 47
1.4 Scope of the Evaluation 48
1.4.1 Conditions of Use Included in the Risk Evaluation 48
1.4.2 Exposure Pathways and Risks Addressed by other EPA Administered Statutes 54
1.4.3 Conceptual Models 60
1.5 Systematic Review 67
1.5.1 Data and Information Collection 67
1.5.2 Data Evaluation 73
1.5.3 Data Integration 74
2 EXPOSURES 75
2.1 Fate and Transport 75
2.1.1 Fate and Transport Approach and Methodology 75
2.1.2 Summary of Fate and Transport 76
2.1.3 Assumptions and Key Sources of Uncertainty for Fate and Transport 77
2.2 Environmental Exposures 77
2,2,1 Environmental Exposures Approach and Methodology 77
Page 2 of 486
-------
2.3 Human Exposure Assessment 78
2.3.1 Occupational Exposures 78
2.3.1.1 Number of Sites and Workers Approach and Methodology 80
2.3.1.2 Inhalation Exposures Approach and Methodology 82
2.3.1.3 Consideration of Engineering Control and Personal Protective Equipment 84
2.3.1.4 Dermal Exposures Approach and Methodology 85
2.3.1.5 Manufacture 85
2.3.1.6 Import 87
2.3.1.7 Processing as a Reactant 88
2.3.1.8 Processing - Incorporation into Formulation, Mixture, or Reaction Product 89
2.3.1.9 Processing - Incorporation into Articles 90
2.3.1.10 Repackaging 91
2.3.1.11 Batch Vapor Degreaser (Open-Top) 92
2.3.1.12 Batch Vapor Degreaser (Closed-Loop) 98
2.3.1.13 In-line Vapor Degreaser (Conveyorized) 100
2.3.1.14 Cold Cleaner 101
2.3.1.15 Aerosol Spray Degreaser/Cleaner 105
2.3.1.16 Dry Cleaning 108
2.3.1.17 Spot Cleaner, Stain Remover 115
2.3.1.18 Adhesive Chemicals (Spray Adhesives) 118
2.3.1.19 THERMAX™ Installation 121
2.3.1.20 Other Uses 122
2.3.1.21 Disposal, Recycling 123
2.3.1.22 Summary oflnhalation Exposure Assessment 124
2.3.1.23 Dermal Exposure Assessment 128
2.3.2 Consumer Exposures 132
2.3.2.1 Consumer Exposures Approach and Methodology 132
2.3.2.2 Consumer Exposure Model (CEM) - Overview, Approach, Inputs, and Results 135
2.3.2.2.1 Aerosol Spray Degreaser/Cleaner-General 142
2.3.2.2.2 Aerosol Spray Degreaser/Cleaner-Electronics 143
2.3.2.2.3 Spot Cleaner and Stain Remover 144
2.3.2.2.4 Spray Cleaner-General 145
2.3.2.2.5 Adhesive Accelerant 147
2.3.2.2.6 Mold Cleaning and Release Product 148
Page 3 of 486
-------
2.3.2.3 Multi-Chamber Concentration and Exposure Model (MCCEM) 149
2.3.2.3.1 Coin and Scissors Cleaner 155
2.3.2.3.2 Automobile AC Flush 156
2.3.2.4 Indoor Environmental Concentrations in Buildings with Conditioned and Unconditioned Zones Model (IECCU)
157
2.3.2.4.1 Insulation (Off-Gassing): Acute Inhalation Exposure 162
2.3.2.4.2 Insulation (Off-Gassing): Chronic Inhalation Exposure 163
2.3.2.5 Summary of Consumer Exposure Assessment 164
2.3.2.6 Key Assumptions, Uncertainties, and Confidence 168
2.4 Potentially Exposed or Susceptible Subpopulations 174
3 HAZARDS (EFFECTS) 177
3.1 Environmental Hazards 177
3.1.1 Approach and Methodology 177
3.1.2 Hazard Identification-Toxicity to Aquatic Organisms 178
3.1.3 Hazard Identification- Toxicity to Terrestrial Organisms 179
J, 1.4 Weight of the Scientific Evidence 180
3.1.5 Concentrations of Concern (COCs) 181
3.1.5.1 Acute COC: 181
3.1.5.2 Chronic COC: 182
3.1.6 Hazard Summary 182
3.2 Human Health Hazard 184
3.2.1 Background on the Process of Systematic Review 184
3.2.2 Approach and Methodology 185
3.2.3 Toxicokinetics 188
3.2.3.1 Biomarkers of Exposure 191
3.2.3.2 PBPK Models 193
3.2.4 Hazard Identification 193
3.2.4.1 Non-Cancer Hazard Identification 194
3.2.4.2 Genotoxicity and Cancer Hazards: Weight of the Scientific Evidence Integration and Mode of Action 198
3.2.5 Evidence Integration and Evaluation of Human Health Hazards 201
3.2.5.1 Weight of the Scientific Evidence for Liver Toxicity 201
3.2.5.2 Weight of the Scientific Evidence for Kidney Toxicity 202
3.2.5.3 Weight of the Scientific Evidence for Immunotoxicity 202
Page 4 of 486
-------
3.2.5.4 Weight of the Scientific Evidence for Reproductive and Developmental Toxicity 202
3.2.5.5 Weight of the Scientific Evidence for Neurotoxicity 203
3.2.5.6 Weight of the Scientific Evidence for Cancer 205
3.2.6 Possible Mode of Action for 1-BP Toxicity 205
3.2.7 Summary of Hazard Studies Used to Evaluate Acute and Chronic Exposures 209
3.2.8 Dose-Response Assessment 209
3.2.8.1 Selection of Studies for Non-Cancer Dose-Response Assessment 209
3.2.8.1.1 PODs for Acute Exposure 211
3.2.8.1.2 PODs for Chronic Exposure 213
3.2.8.1.3 Uncertainty Factor Determinations 214
3.2.8.2 Selection of Studies for Carcinogenic Dose-Response Assessment 222
3.2.8.2.1 Cancer Dose-Response Modeling 222
3.2.8.3 Potentially Exposed or Susceptible Subpopulations 227
3.2.8.4 Points of Departure for Human Health Hazard Endpoints 229
3.2.8.5 Strength, Limitation, and Uncertainty of the Hazard Identification and Selection of PODs for Dose-Response
Assessment 233
4 RISK CHARACTERIZATION 235
4.1 Environmental Risk 235
4.1.1 Aquatic Pathways 235
4.2 Human Health Risk 238
4.2.1 Risk Characterization Approach 238
4.2.2 Occupational Inhalation Exposure Summary and PPE Use Determination by OES 244
4.2.3 Risk Characterization For Acute, Non-Cancer Inhalation Exposures 245
4.2.3.1 Acute Occupational Exposures 246
4.2.3.2 Acute Consumer Exposures 254
4.2.4 Risk Characterization for Chronic Exposure Scenarios 256
4.2.4.1 Non-Cancer MOEs for Chronic, Non-Cancer Occupational Inhalation Exposures and Consumer Insulation (Off-
Gassing) Condition of Use 256
4.2.4.2 Cancer Evaluation for Occupational Scenarios 273
4.2.4.3 Cancer Evaluation for Consumer Scenario (Insulation Off-Gassing) 277
4.2.5 Risk Characterization For Acute and Chronic, Non-Cancer and Cancer Dermal Exposures 278
4.3 Assumptions and Key Sources of Uncertainty 287
4.3.1 Uncertainties of the Occupational Exposure Assessment 287
4.3.1.1 Number of Workers 288
Page 5 of 486
-------
4.3.1.2 Analysis of Occupational Exposure Monitoring Data 288
4.3.1.3 Near-Field / Far-Field Model Framework 289
4.3.1.4 Vapor Degreasing and Cold Cleaning Model 290
4.3.1.5 Aerosol Degreasing Model 291
4.3.1.6 Dry Cleaning Model 292
4.3.1.7 Spot Cleaning Model 293
4.3.1.8 Tank Truck and Railcar Loading and Unloading Release and Inhalation Exposure Model 293
4.3.1.9 Modeling Dermal Exposures 293
4.3.2 Uncertainties of the Consumer Exposure Assessment 294
4.3.2.1 Consumer Use Information 294
4.3.2.2 Model Assumptions and Input Parameters 295
4.3.3 Uncertainties in the Hazard and Dose-Response Assessments 295
4.3.4 Uncertainties in the Risk Assessment 298
4.3.4.1 Environmental Risk Characterization 298
4.3.4.2 Human Health Characterization 301
4.4 Other Risk Related Considerations 302
4.4.1 Potentially Exposed or Susceptible Subpopulations 302
4.4.2 Aggregate and Sentinel Exposures 305
4.5 Risk Conclusions 305
4.5.1 Environmental Risk Conclusions 305
4.5.2 Human Health Risk Conclusions 306
4.5.2.1 Summary of Risk Estimates for Workers and ONUs 306
4.5.2.2 Summary of Risk Estimates for Consumer Users and Bystanders 315
4.5.2.3 Summary of Risk for General Population 318
5 UNREASONABLE RISK DETERMINATION 319
5.1 Overview 319
5.1.1 Human Health 319
5.1.1.1 Non-Cancer Risk Estimates 320
5.1.1.2 Cancer Risk Estimates 320
5.1.1.3 Determining Unreasonable Risk of Injury to Health 321
5.1.2 Environment. 323
5.1.2.1 Determining Unreasonable Risk of Injury to the Environment 323
Page 6 of 486
-------
5.2 Detailed Unreasonable Risk Determinations by Condition of Use 323
5,2.1 Human Health 327
5.2.1.1 Manufacture - Domestic Manufacture (Domestic manufacture) 327
5.2.1.2 Manufacture - Import (Import) 328
5.2.1.3 Processing - Processing as a reactant - Intermediate in all other basic inorganic chemical manufacturing, all
other basic organic chemical manufacturing, and pesticide, fertilizer, and other agricultural chemical manufacturing
(Processing as reactant) 329
5.2.1.4 Processing - Incorporation into formulation, mixture, or reaction products - Solvents for cleaning or degreasing
in manufacturing of: all other chemical product and preparation; computer and electronic product; electrical equipment,
appliance and component; soap, cleaning compound and toilet preparation; and services (Processing into a formulation,
mixture, or reaction product) 330
5.2.1.5 Processing - Incorporation into articles - Solvents (becomes part of product formulation or mixture) in
construction (Processing into articles) 331
5.2.1.6 Processing - Repackaging - Solvents (cleaning or degreasing in all other basic organic chemical manufacturing)
(Processing in repackaging as solvent) 331
5.2.1.7 Processing - Recycling - Recycling (Processing as recycling) 332
5.2.1.8 Distribution in Commerce 333
5.2.1.9 Industrial/Commercial Use - Solvent (for cleaning or degreasing) - Batch vapor degreaser (open-top) and in-line
vapor degreaser (conveyorized, web cleaner) 333
5.2.1.10 Industrial/Commercial Use - Solvent (for cleaning or degreasing) - Batch vapor degreaser (closed-loop)... 3 34
5.2.1.11 Industrial/Commercial Use - Solvent (for cleaning or degreasing) - Cold cleaners 335
5.2.1.12 Industrial/Commercial Use - Solvent (for cleaning or degreasing) - Aerosol spray degreaser/cleaner 336
5.2.1.13 Industrial/Commercial Use - Adhesives and sealants - Adhesive chemicals (spray adhesive for foam cushion
manufacturing and other uses) 337
5.2.1.14 Industrial/Commercial Use - Cleaning and furniture care products - Dry cleaning solvent, spot cleaner and stain
remover 338
5.2.1.15 Industrial/Commercial Use - Cleaning and furniture care products - Liquid cleaner (e.g., coin and scissor
cleaner); liquid spray/aerosol cleaner 339
5.2.1.16 Other Industrial/Commercial Use - Arts, crafts, and hobby materials (adhesive accelerant); automotive care
products (engine degreaser, brake cleaner); anti-adhesive agents (mold cleaning and release product); electronic and
electronic products and metal products; functional fluids - closed systems (refrigerant) and open-systems (cutting oils);
asphalt extraction; laboratory chemicals; and temperature indicator (coatings) 340
5.2.1.17 Consumer Use - Solvent (cleaning or degreasing) - Aerosol spray degreasers/cleaners 341
5.2.1.18 Consumer Use - Cleaning and furniture care products - Spot cleaner and stain remover (Spot cleaners and stain
removers) 342
5.2.1.19 Consumer Use - Cleaning and furniture care products - Liquid cleaner (e.g., coin and scissor cleaner) 343
5.2.1.20 Consumer Use - Cleaning and furniture care products - Liquid spray/aerosol cleaner 343
5.2.1.21 Consumer Use - Other uses - Arts, crafts and hobby materials (adhesive accelerant) 344
5.2.1.22 Consumer Use - Other uses - Automotive care products (refrigerant flush) 345
Page 7 of 486
-------
5.2.1.23 Consumer Use - Other uses - Anti-adhesive agents (mold cleaning and release product) 346
5.2.1.24 Commercial and Consumer Use - Insulation (building/construction materials not covered elsewhere) 347
5.2.1.25 Disposal - Disposal - municipal waste incinerator, off-site waste transfer (Disposal) 347
5.2.1.26 General Population 348
5.2,2 Environment. 348
5.3 Changes to the Unreasonable Risk Determination from Draft Risk Evaluation to Final Risk
Evaluation 349
5.4 Unreasonable Risk Determination Conclusion 351
5.4.1 No Unreasonable Risk Determinations 351
5.4.2 Unreasonable Risk Determinations 352
6 REFERENCES 353
Appendix A REGULATORY HISTORY 376
A, 1 Federal Laws and Regulations 376
A,2 State Laws and Regulations 378
A.3 International Laws and Regulations 379
Appendix B LIST OF SUPPLEMENTAL DOCUMENTS 380
Appendix C FATE AND TRANSPORT 382
C.l Fate in Air 382
C.2 Fate in Water 382
C,3 Fate in Sediment and Soil 383
Appendix D CHEMICAL DATA REPORTING RULE DATA FOR 1-BP 384
Appendix E EXPERIMENTAL MEASUREMENT OF FRACTION ABSORBED FOR
DERMAL EXPOSURE MODELING 385
E. 1 Fabs 385
E.2 Experimental Wind Speed Measurements 386
E,3 Adjustingx andfabs for Wind Speed 387
Appendix F CONSUMER EXPOSURE ASSESSMENT 389
F. 1 Consumer Exposure 389
F.2 Consumer Inhalation Exposure 389
F.3 Consumer Dermal Exposure 390
F.3.1 Comparison of Three Dermal Model Methodologies to Calculate Acute Dose Rate (ADR) 390
F. 3.2 Comparison of Estimated ADRs Across Three Dermal Models 393
F.3.3 Sensitivity Analysis of Three Dermal Models 395
F.3.3.1 Duration of Use 395
F.3.3.2 Fraction Absorbed 395
Page 8 of 486
-------
F.3.3.3 MassTenns 396
F.3.3.4 Weight Fraction 397
F.3.3.5 Permeability Coefficients 398
F.3.3.6 Other Parameters 398
F.3.3.7 Selection of Dermal Models 399
Appendix G ECOSAR Modeling Outputs 400
Appendix H ESTIMATES OF SURFACE WATER CONCENTRATION 402
Appendix I TOXICOKINETICS 405
1.1 Absorption 405
1.2 Distribution 406
13 Metabolism 406
1,4 Elimination 411
Appendix J ANIMAL AND HUMAN TOXICITY STUDIES CONSIDERED FOR USE IN
RISK ASSESSMENT 413
J, 1 Reproductive Toxicity 413
J.2 Neurotoxicity 415
.1.5 Human Case Reports 419
J.4 Human Epidemiology Studies 421
J.5 Carcinogenicity and Mutagenicity 463
J.5.1 Skin Tumors 463
J. 5.2 Large Intestine Tumors 463
J. 5.3 Lung Tumors 464
J. 5.4 Pancreatic Tumors 464
J. 5.5 Malignant Mesothelioma 464
J. 5.6 Genotoxicity 465
J.5.7 Comparison of Bacterial Reverse Mutation Studies 469
J.5.8 Metabolism, Structure-Activity Relationships and Mechanism/Mode of Action 480
Appendix K 1-BP: Mutagenic Mode of Action Analysis 485
Page 9 of 486
-------
LIST OF TABLES
Table 1-1. Physical-Chemical Properties of 1-BP 45
Table 1-2. Production Volume of 1-BP in CDR Reporting Period (2012 to 2015)a 46
Table 1-3. Assessment History of 1-BP 48
Table 1-4. Categories and Subcategories of Conditions of Use Included in the Scope of the Risk
Evaluation 49
Table 2-1. Summary of Environmental Fate and Transport Properties 76
Table 2-2. Crosswalk of Subcategories of Use Listed in the Problem Formulation Document to
Occupational Conditions of Use Assessed in the Final Risk Evaluation 78
Table 2-3. Data Evaluation of Sources Containing General Facility Estimates 81
Table 2-4. Estimated Number of Sites and Workers in the Assessed Occupational Exposure
Scenarios for 1-BP 81
Table 2-5. Data Evaluation of Sources Containing Occupational Exposure Data 83
Table 2-6. Assigned Protection Factors for Respirators in OSHA Standard 29 CFR 1910.134 84
Table 2-7. Summary of 8-hr 1-BP TWA Exposures (AC, ADC and LADC) for Manufacture Based
on Monitoring Data 86
Table 2-8. Summary of 1-BP 8-hr TWA Exposures (AC, ADC and LADC) for Import Based on
Modeling 88
Table 2-9. Summary of 1-BP 8-hr TWA Exposures (AC, ADC and LADC) for Processing as a
Reactant Based on Modeling 89
Table 2-10. Summary of 1-BP 8-hr TWA Exposures (AC, ADC and LADC) for
Processing/Formulation Based on Monitoring Data 90
Table 2-11. Summary of 1-BP 8-hr TWA Exposures (AC, ADC and LADC) for Processing -
Incorporation into Articles Based on Modeling 91
Table 2-12. Summary of 1-BP 8-hr TWA Exposures (AC, ADC and LADC) for Repackaging
Based on Modeling 92
Table 2-13. Summary of 1-BP 8-hr TWA Exposures (AC, ADC and LADC) for Vapor Degreaser
Based on Monitoring Data 94
Table 2-14. Summary of 1-BP 8-hr TWA Exposures (AC, ADC and LADC) for Batch Vapor
Degreaser (Open-Top) Based on Modeling 98
Table 2-15. Summary of 1-BP 8-hr TWA Exposures (AC, ADC and LADC) for Batch Closed-
Loop Vapor Degreasing Based on Modeling 100
Page 10 of 486
-------
Table 2-16. Summary of 1-BP Inhalation Exposure Monitoring Data for Cold Cleaner 103
Table 2-17. Summary of 1-BP 8-hr TWA Inhalation Exposures (AC, ADC and LADC) for Cold
Cleaner Based on Modeling 104
Table 2-18. Summary of 1-BP 8-hr TWA Exposures (AC, ADC and LADC) for Aerosol Spray
Degreaser/Cleaner Based on Monitoring Data 106
Table 2-19. Summary of 1-BP 8-hr TWA Exposures (AC, ADC and LADC) for Aerosol Spray
Degreaser/Cleaner Based on Modeling 108
Table 2-20. Summary of 1-BP 8-hr TWA Exposures (AC, ADC and LADC) for Dry Cleaning
Based on Monitoring Data 110
Table 2-21. Summary of 1-BP Dry Cleaning Exposures for Workers and Occupational Non-users
Based on Modeling 114
Table 2-22. Summary of 1-BP Dry Cleaning Exposures for Children Based on Modeling 114
Table 2-23. Summary of 1-BP 8-hr TWA Exposures (AC, ADC and LADC) for Spot Cleaner
Based on Monitoring Data 116
Table 2-24. Summary of 1-BP 8-hr TWA Exposures (AC, ADC and LADC) for Use of Spot
Cleaner Based on Modeling 117
Table 2-25. Summary of 1-BP 8-hr TWA Exposures (AC, ADC and LADC) for Spray Adhesive
on Monitoring Data 121
Table 2-26. Summary of 1-BP 8-hr TWA Exposures (AC, ADC and LADC) for Disposal Based on
Modeling 124
Table 2-27. Summary of Occupational Inhalation Exposure Results 126
Table 2-28. Glove Protection Factors for Different Dermal Protection Strategies 129
Table 2-29. Estimated Dermal Retained Dose for Workers in All Conditions of Use 131
Table 2-30. Consumer Conditions of Use Assessed in This Risk Evaluation 132
Table 2-31. Consumer Conditions of Use (COUs) and Routes of Exposure Assessed 133
Table 2-32. Crosswalk Between 1-BP Conditions of Use and Westat Product Category 139
Table 2-33. Scenario Specific Varied Input Parameters for the CEM Inhalation Modeling 140
Table 2-34. Aerosol Spray Degreaser/Cleaner-General (Inhalation Exposure Concentrations).... 142
Table 2-35. Aerosol Spray Degreaser/Cleaner-General (Dermal Exposure Doses) 142
Table 2-36. Aerosol Spray Degreaser/Cleaner-Electronics (Inhalation Exposure Concentrations)
143
Page 11 of 486
-------
Table 2-37. Aerosol Spray Degreaser/Cleaner-Electronics (Dermal Exposure Doses) 144
Table 2-38. Spot Cleaner and Stain Remover (Inhalation Exposure Concentrations) 145
Table 2-39. Spot Cleaner and Stain Remover (Dermal Exposure Doses) 145
Table 2-40. Spray Cleaner-General (Inhalation Exposure Concentrations) 146
Table 2-41. Spray Cleaner-General (Dermal Exposure Doses) 146
Table 2-42. Adhesive Accelerant (Inhalation Exposure Concentration) 147
Table 2-43. Adhesive Accelerant (Dermal Exposure Doses) 147
Table 2-44. Mold Cleaning and Release Product (Inhalation Exposure Concentration) 148
Table 2-45. Mold Cleaning and Release Product (Dermal Exposure Doses) 149
Table 2-46. Coin and Scissors Cleaner (Inhalation Exposure Concentration) 155
Table 2-47. Coin and Scissors Cleaner (Dermal Exposure Doses) 155
Table 2-48. Automobile AC Flush (Inhalation Exposure Concentration) 156
Table 2-49. Automobile AC Flush (Dermal Exposure Doses) 156
Table 2-50. Zone Names, Volumes, and Baseline Ventilation Rates 160
Table 2-51. Parameters for the 1-BP Sources 160
Table 2-52. Average 24-Hour TWA Concentration of 1-BP by Zone in Two Building
Configurations 163
Table 2-53. Predicted 1-Year TWA Concentrations by Zone for the Attic/Living Space/Crawl space
Building Configuration 164
Table 2-54. Predicted 1-Year TWA Concentrations by Zone for the Attic/Living Space/Basement
Building Configuration 164
Table 2-55. Inhalation Results Summary 165
Table 2-56. Dermal Results Summary 165
Table 2-57. Inhalation Results Summary-Insulation (Off-Gassing) 168
Table 2-58. Percentage of Employed Persons by Age, Sex, and Industry Sector 175
Table 2-59. Percentage of Employed Persons Age 16-19 Years by Detailed Industry Sector 175
Table 3-1. Ecological Hazard Characterization of 1-BP 184
Table 3-2. Endpoints Selected for the Inhalation Non-Cancer Dose-Response Analysis of 1-BP.216
Page 12 of 486
-------
Table 3-3. Multistage Model, Model-Average (BMDS Version 2.6), and Model-Average (BMDS
Version 3.0) BMC and BMCL Estimates of 1-BP Inhalation Exposure Associated with a 0.1%
Added Risk and 10% Extra Risk of Tumors in Rodents 223
Table 3-4. BMChec and BMCLhec Estimates of 1-BP Inhalation Exposures in Humans Exposed 40
hours/week (8 hours/day, 5 days/week) (ppm) or 24 hrs/day 7 days/week (ppm) 225
Table 3-5. BMDhed and BMDLhed Estimates of 1-BP Dermal Exposures Extrapolated from BMC
and BMCL (mg/kg-day) 225
Table 3-6. Inhalation Unit Risk (IUR) for Humans Exposed via Inhalation Based on Combined
Alveolar/Bronchiolar Adenomas or Carcinomas Observed in Female Mice 226
Table 3-7. Cancer Slope Factor for Humans Exposed via Dermal Contact Extrapolated from
Combined Alveolar/Bronchiolar Adenomas or Carcinomas Observed in Female Mice 227
Table 3-8. HECs/Dermal HEDs Selected for Non-Cancer Effects for 1-BP 230
Table 4-1. Concentrations of Concern (COCs) for Environmental Toxicity as Described in Section
3.1.5 236
Table 4-2. Calculated Risk Quotients (RQs) for 1-BP 237
Table 4-3. Use Scenarios, Populations of Interest and Toxicological Endpoints for Assessing
Occupational Risks Following Acute Exposures to 1-BP 238
Table 4-4. Use Scenarios, Populations of Interest and Toxicological Endpoints for Assessing
Consumer Risks Following Acute/Chronic Exposures to 1-BP 239
Table 4-5. Use Scenarios, Populations of Interest and Toxicological Endpoints for Assessing
Occupational Risks Following Chronic Exposures to 1-BP 241
Table 4-6. Inhalation Exposure Data Summary and Respirator Use Determination 244
Table 4-7. Non-Cancer Risk Estimates for Acute Inhalation Exposures Following Occupational
Use of 1-BP in Manufacture Based on Monitoring Data (U.S.) 247
Table 4-8. Non-Cancer Risk Estimates for Acute Inhalation Exposures Following Occupational
Use of 1-BP in Import, Repackaging, Processing as a Reactant, and Processing - Incorporation into
Articles Based on Modeling 247
Table 4-9. Non-Cancer Risk Estimates for Acute Inhalation Exposures Following Occupational
Use of 1-BP in Processing - Incorporation into Formulation Based on Monitoring Data 247
Table 4-10. Non-Cancer Risk Estimates for Acute Inhalation Exposures Following Occupational
Use of 1-BP in Batch Vapor Degreaser (Open-Top) Based on Monitoring Data 248
Table 4-11. Non-Cancer Risk Estimates for Acute Inhalation Exposures Following Occupational
Use of 1-BP in Batch Vapor Degreaser (Open-Top) Based on Modeling (Pre-ECa) 248
Page 13 of 486
-------
Table 4-12. Non-Cancer Risk Estimates for Acute Inhalation Exposures Following Occupational
Use of 1-BP in Batch Vapor Degreaser (Open-Top) Based on Modeling (Post-ECa) 248
Table 4-13. Non-Cancer Risk Estimates for Acute Inhalation Exposures Following Occupational
Use of 1-BP in Batch Vapor Degreaser (Closed-Loop) Based on Modeling 249
Table 4-14. Non-Cancer Risk Estimates for Acute Inhalation Exposures Following Occupational
Use of 1-BP in Cold Cleaner Based on Monitoring Data 249
Table 4-15. Non-Cancer Risk Estimates for Acute Inhalation Exposures Following Occupational
Use of 1-BP in Cold Cleaner Based on Modeling 249
Table 4-16. Non-Cancer Risk Estimates for Acute Inhalation Exposures Following Occupational
Use of 1-BP in Aerosol Spray Degreaser Based on Monitoring Data (Pre-ECa) 250
Table 4-17. Non-Cancer Risk Estimates for Acute Inhalation Exposures Following Occupational
Use of 1-BP in Aerosol Spray Degreaser Based on Monitoring Data (Post-ECa) 250
Table 4-18. Non-Cancer Risk Estimates for Acute Inhalation Exposures Following Occupational
Use of 1-BP in Aerosol Spray Degreaser Based on Modeling 250
Table 4-19. Non-Cancer Risk Estimates for Acute Inhalation Exposures Following Occupational
Use of 1-BP in Dry Cleaning Based on Monitoring Data 251
Table 4-20. Non-Cancer Risk Estimates for Acute Inhalation Exposures Following Occupational
Use of 1-BP in Dry Cleaning Based on Modeling (3rd Generation Machine) 252
Table 4-21. Non-Cancer Risk Estimates for Acute Inhalation Exposures Following Occupational
Use of 1-BP in Dry Cleaning Based on Modeling (4th Generation Machine) 252
Table 4-22. Non-Cancer Risk Estimates for Acute Inhalation Exposures Following Occupational
Use of 1-BP in Spot Cleaner Based on Monitoring Data 252
Table 4-23. Non-Cancer Risk Estimates for Acute Inhalation Exposures Following Occupational
Use of 1-BP in Spot Cleaner Based on Modeling 253
Table 4-24. Non-Cancer Risk Estimates for Acute Inhalation Exposures Following Occupational
Use of 1-BP in Adhesive Chemicals (Spray Adhesivea) Based on Monitoring Data (Pre-EC) 253
Table 4-25. Non-Cancer Risk Estimates for Acute Inhalation Exposures Following Occupational
Use of 1-BP in Adhesive Chemicals (Spray Adhesive) Based on Monitoring Data (Post-ECa)....254
Table 4-26. Non-Cancer Risk Estimates for Acute Inhalation Exposures Following Occupational
Use of 1-BP in Disposal Based on Modeling 254
Table 4-27. Non-Cancer Risk Estimates for Acute 24-hr Inhalation Exposure Following Consumer
Uses of 1-BP (Benchmark MOE = 100) Based on Modeling 255
Table 4-28. Non-Cancer Risk Estimates for Chronic Inhalation Exposures Following Occupational
Use of 1-BP in Manufacture (U.S.) Based on Monitoring Data 257
Page 14 of 486
-------
Table 4-29. Non-Cancer Risk Estimates for Chronic Inhalation Exposures Following Occupational
Use of 1-BP in Import, Processing as a Reactant, and Processing - Incorporation into Articles
Based on Modeling 258
Table 4-30. Non-Cancer Risk Estimates for Chronic Inhalation Exposures Following Occupational
Use of 1-BP in Processing - Incorporation into Formulation Based on Monitoring Data 258
Table 4-31. Non-Cancer Risk Estimates for Chronic Inhalation Exposures Following Occupational
Use of 1-BP in Batch Vapor Degreaser (Open-Top) Based on Monitoring Data 259
Table 4-32. Non-Cancer Risk Estimates for Chronic Inhalation Exposures Following Occupational
Use of 1-BP in Batch Vapor Degreaser (Open-Top) (Pre-EC) Based on Modeling 260
Table 4-33. Non-Cancer Risk Estimates for Chronic Inhalation Exposures Following Occupational
Use of 1-BP in Batch Vapor Degreaser (Open-Top) (Post-EC) Based on Modeling 261
Table 4-34. Non-Cancer Risk Estimates for Chronic Inhalation Exposures Following Occupational
Use of 1-BP in Batch Vapor Degreaser (Closed-Loop) Based on Modeling 261
Table 4-35. Non-Cancer Risk Estimates for Chronic Inhalation Exposures Following Occupational
Use of 1-BP in Cold Cleaner Based on Monitoring Data 262
Table 4-36. Non-Cancer Risk Estimates for Chronic Inhalation Exposures Following Occupational
Use of 1-BP in Cold Cleaner Based on Modeling 263
Table 4-37. Non-Cancer Risk Estimates for Chronic Inhalation Exposures Following Occupational
Use of 1-BP in Aerosol Spray Degreaser/Cleaner (Pre-ECa) Based on Monitoring Data 263
Table 4-38. Non-Cancer Risk Estimates for Chronic Inhalation Exposures Following Occupational
Use of 1-BP in Aerosol Spray Degreaser/Cleaner (Post-ECa) Based on Monitoring Data 265
Table 4-39. Non-Cancer Risk Estimates for Chronic Inhalation Exposures Following Occupational
Use of 1-BP in Aerosol Spray Degreaser/Cleaner Based on Modeling 266
Table 4-40. Non-Cancer Risk Estimates for Chronic Inhalation Exposures Following Occupational
Use of 1-BP in Adhesive Chemicals (Spray Adhesives) (Pre-ECa) Based on Monitoring Data....267
Table 4-41. Non-Cancer Risk Estimates for Chronic Inhalation Exposures Following Occupational
Use of 1-BP in Adhesive Chemicals (Spray Adhesives) (Post-ECa) Based on Monitoring Data ..267
Table 4-42. Non-Cancer Risk Estimates for Chronic Inhalation Exposures Following Occupational
Use of 1-BP in Dry Cleaning Based on Monitoring Data 268
Table 4-43. Non-Cancer Risk Estimates for Chronic Inhalation Exposures Following Occupational
Use of 1-BP in Dry Cleaning Based on Modeling (3rd Generation)
Table 4-44. Non-Cancer Risk Estimates for Chronic Inhalation Exposures Following Occupational
Use of 1-BP in Dry Cleaning Based on Modeling (4th Generation)
.269
.269
Page 15 of 486
-------
Table 4-45. Non-Cancer Risk Estimates for Chronic Inhalation Exposures Following Occupational
Use of 1-BP in Spot Cleaner Based on Monitoring Data 270
Table 4-46. Non-Cancer Risk Estimates for Chronic Inhalation Exposures Following Occupational
Use of 1-BP in Spot Cleaner Based on Modeling 271
Table 4-47. Non-Cancer Risk Estimates for Chronic Inhalation Exposures Following Occupational
Use of 1-BP in Disposal Based on Modeling 272
Table 4-48. Non-Cancer Risk Estimates for Chronic Inhalation Exposures Following Installation of
THERMAX™ Rigid Insulation Board Within a Residence Based on Modeling 272
Table 4-49. Inhalation Cancer Risk Estimates for Occupational Use of 1-BP (Benchmark = lxlO"4)
274
Table 4-50. Inhalation Cancer Risk Estimates Under the Insulation (Off-Gassing) Condition of Use
for the Consumer Bystander 278
Table 4-51. Non-Cancer Risk Estimates for Acute and Chronic Dermal Exposures Following
Occupational Use of 1-BP in Manufacture, Import, Processing, and Disposal (Bin 1, Benchmark =
100) 279
Table 4-52. Non-Cancer Risk Estimates for Acute and Chronic Dermal Exposures Following
Occupational Use of 1-BP in Vapor Degreaser and Cold Cleaner (Bin 2, Benchmark = 100) 280
Table 4-53. Non-Cancer Risk Estimates for Acute and Chronic Dermal Exposures Following
Occupational Use of 1-BP in Spray Adhesive (Bin 3, Benchmark = 100) 281
Table 4-54. Non-Cancer Risk Estimates for Acute and Chronic Dermal Exposures Following
Occupational Use of 1-BP in Dry Cleaning and Spot Cleaner (Bin 4, Benchmark = 100) 282
Table 4-55. Non-Cancer Risk Estimates for Acute and Chronic Dermal Exposures Following
Occupational Use of 1-BP in Aerosol Spray Degreaser/Cleaner, Other Aerosol and Non-aerosol
Uses (Bin 5, Benchmark = 100) 283
Table 4-56. Cancer Risk Estimates for Dermal Exposure Following Occupational Use of 1-BP..284
Table 4-57. Non-Cancer Risk Estimates for Acute 24-hr Dermal Exposure Following Consumer
Uses of 1-BP 285
Table 4-58. Occupational Risk Summary Table 308
Table 4-59. Consumer Risk Summary Table 316
Table 5-1. Categories and Subcategories of Conditions of Use Included in the Scope of the Risk
Evaluation 323
Page 16 of 486
-------
LIST OF APPENDIX TABLES
Table_Apx A-l. Federal Laws and Regulations 376
Table_Apx A-2. State Laws and Regulations 378
Table_Apx A-3. Regulatory Actions by other Governments and Tribes 379
TableApx D-l. National Chemical Information for 1-BP from 2012 CDR 384
TableApx D-2. Summary of Industrial 1-BP Uses from 2012 CDR 384
Table Apx D-3. Commercial/Consumer Use Category Summary of 1-BP 384
Table Apx F-l. Example Structure of CEM Cases Modeled for Each consumer Product/Article
Use Scenario 389
Table Apx F-2. Comparison of Adult Acute Dermal Exposure Estimates from Three Dermal
Models 393
Table Apx H-l. Estimated Surface Concentrations from Water Releases Reported to TRI 403
Table_Apx J-l. Case Reports on 1-BP 419
Table Apx J-2. Summary of the Toxicological Database for 1-BP 425
Table Apx J-3. Tumors induced by 1-BP in Rats and Mice 465
Table_Apx J-4. Key Genotoxicity Studies on 1-BP 468
Table Apx J-5. Comparison of Mean Numbers of Revertants/Plate for Controls in Reverse
Mutation Assays 472
Table_Apx J-6. Comparison of Mutagenicity Studies of 1-BP 475
Table Apx K-l. Decisions and Justification Relating to Mutagenic Mode of Action Analysis for 1-
BP (see Figure 1 from (U.S. EPA, 2005b) 486
LIST OF FIGURES
Figure 1-1. Chemical Structure of 1-Bromopropane 45
Figure 1-2. 1-BP Life Cycle Diagram 53
Figure 1-3. 1-BP Conceptual Model for Industrial and Commercial Activities and Uses: Potential
Exposures and Hazards 62
Figure 1-4. 1-BP Conceptual Model for Consumer Activities and Uses: Potential Exposures and
Hazards 63
Page 17 of 486
-------
Figure 1-5. 1-BP Conceptual Model for Environmental Releases and Wastes: Potential Exposures
and Hazards 65
Figure 1-6. Literature Flow Diagram for Environmental Fate and Transport Data Sources 69
Figure 1-7. Literature Flow Diagram for Environmental Release and Occupational Exposure Data
Sources 70
Figure 1-8. Literature Flow Diagram for Consumer and Environmental Exposure Data Sources...71
Figure 1-9. Literature Flow Diagram for Environmental Hazard Data Sources 72
Figure 2-1. Open-Top Vapor Degreaser with Enclosure 93
Figure 2-2. Schematic of the Near-Field/Far-Field Model for Vapor Degreasing 95
Figure 2-3. Closed-loop/Vacuum vapor Degreaser 99
Figure 2-4. Typical Batch-Loaded, Maintenance Cold Cleaner (U.S. EPA, 1981) 102
Figure 2-5. The Near-Field/Far-field Model for Cold Cleaning Scenario 104
Figure 2-6. Overview of Aerosol degreasing 105
Figure 2-7. Schematic of the Near-Field/Far-Field Model for Aerosol degreasing 107
Figure 2-8. Overview of Dry Cleaning 109
Figure 2-9. Illustration of the Multi-Zone Model 112
Figure 2-10. Overview of Use of Spot Cleaning at Dry Cleaners 115
Figure 2-11. Schematic of the Near-Field/Far-Field Model for Spot Cleaning 117
Figure 2-12. Overview of Use of Spray Adhesive in the Furniture Industry 118
Figure 2-13. The Three-Zone Configuration for a Residential Setting and Baseline Ventilation and
Interzonal Air Flows for the Attic/Living Space/Crawl space Building Configuration 159
Figure 2-14. The Three-Zone Configuration for a Residential Setting and Baseline Ventilation and
Interzonal Air Flows for the Attic/Living Space/Full Basement Building Configuration 160
Figure 2-15. 24-Hour TWA Concentrations for Attic/Living Space/Crawl space Building
Configuration Across Four Different Installation Dates 161
Figure 2-16. 24-Hour TWA Concentrations for Attic/Living Space/Full Basement Building
Configuration Across Four Different Installation Dates 162
Figure 2-17 Predicted Gas-Phase 1-BP Concentration (Mg/M3) in Three Locations Within the
Attic/Living Space/Crawl space Building Configuration 167
Figure 2-18. Predicted Gas-Phase 1-BP Concentrations (Mg/M3) in Three Locations Within the
Attic/Living Space/Crawl space Building Configuration 167
Page 18 of 486
-------
Figure 3-1. EPA Approach to Hazard Identification, Data Integration, and Dose-Response Analysis
for 1 -BP 186
Figure 3-2. Metabolism of 1-Bromopropane in Male F-344 Rats and B6C3F1 Mice Following
Inhalation Exposure or Tail Vein Injection* 190
Figure 3-3. Proposed Intermediary Metabolism for 1-BP 208
Figure 4-1. Central Tendency Inhalation Cancer Risk Estimates for Occupational Use of 1-BP ..276
Figure 4-2. High-End Inhalation Cancer Risk Estimates for Occupational Use of 1-BP 277
LIST OF APPENDIX FIGURES
FigureApx E-l. Distribution of Mean Indoor Wind Speed as Measured by Baldwin and Maynard
(1998) 387
Figure Apx 1-1. Formation of N-Acetyl-S-Propylcysteine from 1-Bromopropane Via Conjugation
with Reduced Glutathione (GSH) 407
Figure Apx 1-2. Mercapturic Acid Metabolites with a Sulfoxide Group or a Hydroxyl or Carbonyl
Group on the Propyl Residue Identified in Urine Samples of 1-Bromopropane-Exposed Workers
408
Figure Apx K-l. 1-BP Mutagenic MOA Weight of the Scientific Evidence Determination
Following the Supplemental Guidance 1 for Assessing Susceptibility from Early-Life Exposure to
Carcinogens 485
LIST OF EQUATIONS
Equation 2-1. Equation for Calculating Vapor Degreasing Vapor Generation Rate 96
Equation 2-2. Equation for Calculating Occupational Dermal Exposure 128
Equation 4-1. Equation to Calculate Non-Cancer Risks Following Acute or Chronic Exposures
Using Margin of Exposures 242
Equation 4-2. Equation to Calculate Extra Cancer Risks 243
Page 19 of 486
-------
LIST OF APPENDIX EQUATIONS
EquationApx E-l. Ratio of Evaporative Flux to Absorption Flux (x) 385
EquationApx E-2. Liquid-Phase Evaporation Mass Transfer Coefficient 385
Equation_Apx E-3. Gas-Phase Mass Transfer Coefficient 386
Equation_Apx E-4. Adjusted Dermal Evaporative Flux 387
Equation_Apx E-5. Adjusted Vapor Pressure 387
Equation_Apx F-l. CEM Permeability Model, Acute Dose Rate 390
Equation Apx F-2. CEM Permeability Model, Permeability Coefficient Kp 391
Equation Apx F-3. CEM Absorption Fraction Model, Acute Dose Rate 391
Equation Apx F-4. CEM Absorption Fraction Model, Amount Retained on Skin 391
Equation Apx F-5. CEM Absorption Fraction Model, Fraction Absorbed 391
Equation_Apx F-6. CEM Absorption Fraction Model, % 392
Equation_Apx F-7. Frasch, Acute Dose Rate 392
Equation_Apx F-8. Frasch. Total Mass Absorbed mi 392
Equation Apx F-9. Frasch, Mass Absorbed at End of Exposure Time mabs(texP) 393
EquationApx F-10. Frasch, Mass at the End of Exposure Time mo 393
Equation_Apx F-l 1. Frasch, Fraction Absorbed Fabs 393
Page 20 of 486
-------
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).
Authors
Stan Barone (Deputy Division Director), Nhan Nguyen (Management Lead), Katherine Anitole
(Staff Lead), Ariel Hou (Staff Lead), Kevin Vuilleumier (Staff Lead), Chris Brinkerhoff, Ana
Corado, Susan Euling, Zaida Figueroa, Garrett Jewett, David Lynch, Greg Macek, Paul Matthai,
Bethany Masten, Albert Monroe, Alie Muneer, Sharon Oxendine, Andrea Pfahles-Hutchens,
Shannon Rebersak, Mitchell Sumner, Amy Shuman, Eva Wong, Yintak Woo (formerly with EPA)
Contributors
Johanna Congleton (EPA/ORD), Catherine Gibbons (EPA/ORD), Jeff Gift (EPA/ORD), Roman
Mezencey (EPA/ORD), Ravi Subramaniam (EPA/ORD), Lily Wang (EPA/ORD), Scott Masten
(NM), Diane Spencer (NIH), Shannon Berg (CDC/NIOSH), Robert Daniels (CDC/NIOSH),
Senthilkumar Perumal Kuppusamy (CDC/NIOSH), Thomas Lentz (CDC/NIOSH), Richard
Niemeier (CDC/NIOSH), Christine Whittaker (CDC/NIOSH)
Acknowledgements
The OPPT Assessment Team gratefully acknowledges participation 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 GDIT (Contract No. CIO-SP3,
HHSN316201200013W), ERG (Contract No. EP-W-12-006), Versar (Contract No. EP-W-17-006),
ICF (Contract No. EPC14001), SRC (Contract No. EP-W-12-003), and Abt Associates (Contract
No. EPW-16-009).
Docket
Supporting information can be found in public docket KPA-f IQ-OPPT-2019-0235.
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.
Page 21 of 486
-------
ABBREVIATIONS
AC
Acute concentration
ACGM
American Conference of Governmental Industrial Hygienists
ACH
Air changes per hour
ADAF
Age-dependent adjustment factor
ADC
Average daily concentration
ADR
Acute dose rate
ADRpot
Potential acute dose rate
AEGL
Acute exposure guideline level
AER
Air exchange rate
APF
Assigned protection factor
Apx
Appendix
AT
Averaging time
Atm
Atmosphere
AT SDR
Agency for Toxic Substances and Disease Registry
BAF
Bioaccumulation factor
BCF
Bioconcentration factor
BL
Baseline
BMCL
Benchmark concentration, lower confidence limit(s)
BMD
Benchmark dose
BMDL
Benchmark dose, lower confidence limit(s)
BMR
Benchmark response level
BLS
Bureau of Labor Statistics
BOD
Biochemical oxygen demand
BOP
3 -Bromo-1 -hy droxypropanone
BW
Body weight
C
Contaminant concentration
Cair
Air concentration
Page 22 of 486
-------
°c
Degree Celsius
CAA
Clean Air Act
Cff
Average far field concentration
Cfftwa
Time weighted average far field concentration
CNF
Average near field concentration
CNFtwa
Time weighted average near field concentration
Cp pot
Modeled peak concentration
CASRN
Chemical Abstracts Service Registry Number
CBI
Confidential business information
CCD
Chemical Control Division
CCRIS
Chemical Carcinogenesis Research Information System
CDR
Chemical Data Reporting
CEM
Consumer exposure module
CESSD
Chemistry, Economics, and Sustainable Strategies Division
CI
Confidence interval
cm
Centimeter(s)
cm3
Cubic meter(s)
CNS
Central nervous system
C02
Carbon dioxide
coc
Concentration of Concern
CSAC
Chemical Safety Advisory Committee
CYP
Cytochrome P450
DEv
Duration of an event
DIY
Do-it-yourself
DNA
Deoxyribonucleic acid
EC
Engineering controls
ECA
Enforceable consent agreement
ED
Exposure duration
Page 23 of 486
-------
EF
Exposure frequency
E-FAST2
Exposure and Fate Assessment Screening Tool Version 2
EFH
Exposure Factors Handbook
EMIC
Environmental Mutagens Information Center
EPA
Environmental Protection Agency
ERG
Eastern Research Group, Inc.
EU
European Union
EvapTime
Evaporation time
FF
Far field
FQ
Frequency of product use
FSA
Free surface area
ft
Foot/feet
ft2
Square foot/feet
ft3
Cubic foot/feet
g
Gram(s)
g/cm3
Grams per cubic centimeters
g/L
Grams per liter
G
Average generation rate
GM
Geometric mean
GSD
Geometric standard deviation
GD
Gestational day
GENE-TOX
Genetic Toxicology Data Bank
GSH
Glutathione (reduced)
Hnf
Near field height
HAPs
Hazardous air pollutants
HCV
Human cancer value
HEC
Human equivalent concentration
HED
Human equivalent dose
Page 24 of 486
-------
HHE
Health Hazard Evaluation
hr
Hour(s)
HSDB
Hazardous Substances Data Bank
HSIA
Halogenated Solvents Industry Alliance
IA
Indoor air
I ARC
International Agency for Research on Cancer
IMIS
Integrated Management Information System
InhR
Inhalation rate
IRIS
Integrated Risk Information System
IUR
Inhalation unit risk
k
Emission rate
Kow
Octanol: water partition coefficient
kg
Kilogram(s)
Koc
Soil organic carbon-water partitioning coefficient
L
Liter(s)
lb
Pound(s)
Lnf
Near field length
LA DC
Lifetime average daily concentration
LADD
Lifetime average daily dose
LEV
Local exhaust ventilation
LT
Lifetime
LOAEL
Lowest-ob served-adverse-effect level
MA
Model-averaging
m
Meter(s)
m2
Square meter(s)
m3
Cubic meter(s)
MCCEM
Multi-Chamber Concentration and Exposure Model
[j,g/m3
Microgram(s) per cubic meter
Page 25 of 486
-------
mg
Milligram(s)
mg/kg-bw
Milligram(s) per kilogram body weight
mg/L
Milligram(s) per liter
mg/m3
Milligram(s) per cubic meter
mg/mL
Milligram(s) per milliliter
min
Minute(s)
MITI
Ministry of International Trade and Industry
Mlbs
Million of pounds
mm Hg
Millimeters of mercury
MMOA
Mutagenic Mode of Action
MOA
Mode of Action
MOE
Margin of exposure
MOEacute
Margin of exposure for acute exposures
MOEchronic
Margin of exposure for chronic exposures
MOU
Memorandum of understanding
MW
Molecular weight
NAICS
North American Industry Classification System
NAPL
Nonaqueous phase liquid
NAS
National Academies of Science
NCI
National Cancer Institute
NCTR
National Center for Toxicological Research
NLogistic
Nested Logistic
NEI
National Emissions Inventory
NESHAP
National Emissions Standards for Hazardous Air Pollutants
NF
Near field
NF/FF
Near field/far field
NHANES
National Health and Nutrition Examination Survey
NICNAS
National Industrial Chemicals Notification and Assessment Scheme
Page 26 of 486
-------
NIH
National Institutes of Health
NIOSH
National Institute for Occupational Safety and Health
NIST
National Institute of Standards and Technology
nm
Nanometer(s)
NOAEL
No-observed-adverse-effect level
NOES
National Occupational Exposure Survey
NOHSC
National Occupational Health and Safety Commission
NJDEP
New Jersey Department of Environmental Protection
NPS
Nonpoint source
NTP
National Toxicology Program
OAR
Office of Air and Radiation
OCSPP
Office of Chemical Safety and Pollution Prevention
OECD
Organization for Economic Co-operation and Development
ONU
Occupational non-user
OPPT
Office of Pollution Prevention and Toxics
OR
Odds ratio
OSHA
Occupational Safety and Health Administration
OSWER
Office of Solid Waste and Emergency Response
OW
Office of Water
oz
Ounce(s)
PA
Personal air
PBZ
Personal breathing zone
PEL
Permissible exposure limit
PESS
Potentially exposed or susceptible subpopulations
PERC
Perchloroethylene
PID
Photoionization detector
PND
Postnatal day
POD
Point of departure
Page 27 of 486
-------
POTW
ppb
ppm
PS
PVC
Qff
Qnf
QA
QC
RCRA
REACH
RfC
RfD
RR
RTECS
s
SAB
SARA
SCG
SD
SDS
SDWA
SNAP
SVHC
t
TCA
TCE
TOXLINE
Publicly Owned Treatment Works
Parts per billion
Parts per million
Point Source
Polyvinyl chloride
Far field ventilation rate
Near field ventilation rate
Quality assurance
Quality control
Resource Conservation and Recovery Act
Registration Evaluation Authorization and Restriction of Chemicals
Reference concentration
Reference dose
Rate ratio
Registry of Toxic Effects of Chemical Substances
Second(s)
Science Advisory Board
Superfund Amendments and Reauthorization Act
Scientific Consulting Group, Inc.
Standard deviation
Safety data sheet(s)
Safe Drinking Water Act
Significant New Alternative Policy for ozone depleting substances
Substance of Very High Concern
Time
Trichloroacetic acid
T ri chl oroethy 1 ene
Toxicology Literature Online
Page 28 of 486
-------
TRI
Toxics Release Inventory
TSCA
Toxic Substances Control Act
TWA
Time-weighted average
UF
Uncertainty factor
UFs
Subchronic to chronic uncertainty factor
UFa
Interspecies uncertainty factor
UFh
Intraspecies uncertainty factor
UFl
LOAEL to NOAEL uncertainty factor
UFd
Database uncertainty factor
US EPA
United States Environmental Protection Agency
Vff
Far field volume
VNF
Indoor wind speed
Vnf
Near field volume
voc
Volatile organic compound
VP
Vapor pressure
WWTP
Waste water treatment plant
WNF
Near field width
WY
Working years
Yr (s)
Year(s)
Page 29 of 486
-------
EXECUTIVE SUMMARY
This risk evaluation for 1-bromopropane (or 1-BP) was performed in accordance with the Frank R.
Lautenberg Chemical Safety for the 21st Century Act and is being issued following 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. Under the amended statute, EPA is required, under TSCA § 6(b), to conduct risk
evaluations to determine whether a chemical substance presents unreasonable risk of injury to
health or the environment, under the conditions of use, without consideration of costs or other non-
risk factors, including an unreasonable risk to potentially exposed or susceptible subpopulations,
identified as relevant to the risk evaluation. Also, as required by TSCA § (6)(b), EPA established,
by rule, a process to conduct these risk evaluations, Procedures for Chemical Risk Evaluation
Under the Amended Toxic Substances Control Act ( 26) (Risk Evaluation Rule). This risk
evaluation is in conformance with TSCA § 6(b), and the Risk Evaluation Rule, and is to be used to
inform risk management decisions. In accordance with TSCA Section 6(b), if EPA finds
unreasonable risk from a chemical substance under its conditions of use in any final risk
evaluation, the Agency will propose actions to address those risks within the timeframe required by
TSCA. However, any proposed or final determination that a chemical substance presents
unreasonable risk under TSCA Section 6(b) is not the same as a finding that a chemical substance
is "imminently hazardous" under TSCA Section 7. The conclusions, findings, and determinations
in this final 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 TSCA Section 7.
TSCA § 26(h) and (i) require EPA, when conducting risk evaluations, 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 (U.S. EPA. 2018a). The
data collection, evaluation, and integration stages of the systematic review process are used to
develop the exposure, fate, and hazard assessments for risk evaluations. To satisfy requirements in
TSCA Section 26(j)(4) and 40 CFR 702.51(e), EPA has provided a list of studies considered in
carrying out the risk evaluation, and the results of those studies are included in the Systematic
Review Data Quality Evaluation Documents (see Appendix B, items 1 through 10).
1-BP has a wide-range of uses, including as a solvent for cleaning and degreasing (including vapor
degreasing, cold cleaning, and aerosol degreasing). A variety of consumer and commercial
products use 1-BP as adhesives and sealants, in furniture care products, in dry cleaning, spot
cleaning and other liquid, spray, and aerosol cleaners, and in automotive care products. 1-BP is
subject to federal and state regulations and reporting requirements. 1-BP has been a reportable
Toxics Release Inventory (TRI) chemical under Section 313 of the Emergency Planning and
Community Right-to-Know Act (EPCRA) since 2016. It is listed under the Clean Air Act (CAA),
under the National Volatile Organic Compound Emission Standards for Aerosol Coatings (40 CFR
Page 30 of 486
-------
Part 59 Subpart E). and is under Section 612 of the CAA, under the Significant New Alternatives
Policy (SNAP) program.
EPA evaluated the following categories of conditions of use: manufacturing; processing;
distribution in commerce; industrial, commercial and consumer uses; and disposal.1 Total
production volume (domestic manufacture plus import) of 1-BP has increased from 2012 to 2015
(U.S. EPA. 2016a). 1-BP's volume has increased because it has been an alternative to ozone-
depleting substances and chlorinated solvents. Import volumes for 1-BP reported to the 2016 CDR
are between 10 million and 25 million pounds per year (U.S. EPA. 2016a).
Approach
EPA used reasonably available information (defined in 40 CFR 702.33 as "information that EPA
possesses, or can reasonably 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 published
since the publication of previous analyses. 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 (U.S. EPA. 2018a).
In the Scope Document (U.S. EPA. 2017d) and Problem Formulation (U.S. EPA. 2018c). EPA
identified the conditions of use and presented three conceptual models and an analysis plan for this
risk evaluation. These have been carried into this final risk evaluation where EPA has
quantitatively and qualitatively evaluated the risk to the environment and human health, using both
monitoring data (when reasonably available) and modeling approaches, for the conditions of use
within the scope of the risk evaluation (identified in Section 1.4.1 of this final risk evaluation).2
EPA carried out a quantitative and qualitative assessment of the following:
• Risks to terrestrial and sediment-dwelling aquatic species from exposure to water and soil
by considering physical-chemical and fate properties of 1-BP. Risks to aquatic species in
the water column from releases to surface water by comparing estimated environmental
exposures to available environmental hazard data.
1 Although EPA has identified both industrial and commercial uses here for purposes of distinguishing scenarios in this
analysis, the Agency interprets the authority to cover "any manner or method of commercial use" under TSCA Section
6(a)(5) to reach both.
2 EPA did not identify any "legacy uses" or "associated disposals" of 1-BP, as those terms are described in EPA's Risk
Evaluation Rule, 82 FR 33726 (July 20, 2017). Therefore, no such uses or disposals were added to the scope of the risk
evaluation for 1-BP following the issuance of the opinion in Safer Chemicals, Healthy Families v. EPA, 943 F.3d 397
(9th Cir. 2019).
Page 31 of 486
-------
• Risk to workers from inhalation and dermal exposures and to occupational non-users
(ONUs)3 from inhalation exposures, by comparing the estimated acute and chronic
exposures to human health hazards.
• Risks to consumers from inhalation and dermal exposures and to bystanders from
inhalation exposures, by comparing the estimated acute exposures to human health
hazards.
• Risk to bystanders from inhalation exposures from insulation (off-gassing), as described in
Section 2.3.2.4, by comparing the estimated chronic exposures to (non-cancer and cancer)
health hazards.
• Risks to general population from exposure to water, sediment, and soil by considering
physical-chemical properties, environmental fate properties, and environmental release
estimates.
In the Problem Formulation, EPA conducted a preliminary analysis of risks to terrestrial and
aquatic species based on the potential exposure pathways through air, water, and soil identified in
the conceptual model for environmental releases and wastes (Figure 1-5). This preliminary
environmental risk assessment qualitatively considered the physical-chemical and environmental
fate properties (high volatility, high water solubility and low Log Kow) to determine that risks were
not likely for terrestrial and sediment-dwelling aquatic species due to the low potential for
exposure. These approaches were initially presented in the Problem Formulation and are brought
forward to this document to make a final risk determination because the initial evaluation was
sufficient to make a risk determination. EPA preliminarily characterized potential risks to water
column dwelling aquatic species quantitatively by conducting a screening-level assessment that
calculated risk quotients (RQ) by comparing estimated environmental concentrations to
environmental hazard data for aquatic species to identify potential risks to aquatic organisms. TRI
data were used to estimate exposures to water-column-dwelling aquatic organisms from releases to
surface water. In the Problem Formulation as well as the draft Risk Evaluation, hazard thresholds,
known as Concentrations of Concern (COCs) were calculated for aquatic species using reasonably
available environmental hazard data, which included a single acute fish toxicity study identified in
the Ecological Hazard Literature Search Results for 1-BP, as well as summaries of environmental
hazard data identified for 1-BP in the ECHA Database. As explained in Sections 3.1 and 4.1, the
preliminary risk assessment for water column-dwelling aquatic species was updated in this final
risk evaluation due to uncertainties about the data presented in summary format in the ECHA
database.
EPA attempted to obtain the full study reports for the environmental hazard data summaries
described in ECHA, which were used the draft risk evaluation. After conducting outreach efforts,
EPA was unable to identify a US-based data owner of the full study reports and review these
studies for data quality. Because EPA could not obtain these full study reports, the discussion of
the data in the ECHA study summaries was removed from the final risk assessment. In contrast,
3 ONUs are workers who do not directly handle 1-BP but perform work in an area where 1-BP is present.
Page 32 of 486
-------
EPA reviewed a single acute fish toxicity study in the environmental hazard data using the data
quality review evaluation metrics and the rating criteria described in the Application of Systematic
Review in TSCA Risk Evaluations (U.S. EPA. 2018a). where it was rated high quality. To reduce
uncertainties about relying on a single acute fish study to characterize environmental hazard to all
aquatic species across acute and chronic exposure, EPA incorporated ECOSAR (v2.0) (EPA. 2017)
modeling4 results into the discussion of environmental hazard and risk, a commonly utilized
practice for the environmental hazard assessment of new chemical substances. These predicted
hazard endpoints were in agreement with the single fish study in that they both indicated the 1-BP
presents a moderate hazard. The result of the analysis conducted using the acute fish study and
ECOSAR modeling (v.2.0) (EPA. 2017) did not identify risks to aquatic species under the
conditions of use within the scope of the risk evaluation.
EPA evaluated exposures to 1-BP in occupational and consumer settings for the conditions of use
included in the scope of the risk evaluation, listed in Section 1.4. In occupational settings, EPA
evaluated acute and chronic inhalation exposures to workers and ONUs, and acute and chronic
dermal exposures to workers. EPA used inhalation monitoring data from literature sources, where
reasonably available and that met data evaluation criteria, as well as modeling approaches, where
reasonably available, to estimate potential inhalation exposures. Dermal doses for workers were
modeled in these scenarios since dermal monitoring data were not reasonably available. In
consumer settings, EPA evaluated acute inhalation exposures to both consumers and bystanders,
and acute dermal exposures to consumers. EPA also evaluated chronic inhalation exposure to
bystanders resulting from off-gassing of 1-BP from rigid board insulation installed within a
residence. Inhalation exposures and dermal doses in these scenarios were modeled since inhalation
and dermal monitoring data were not reasonably available. These analyses are described in Section
2.3 of this risk evaluation.
EPA evaluated reasonably available information for human health hazards and identified hazard
endpoints for non-cancer effects and cancer effects following acute and chronic exposures. EPA
used the Framework for Human Health Risk Assessment to Inform Decision Making (U. S. EPA.
2014c) to evaluate, extract, and integrate 1-BP's human health hazard and dose-response
information. EPA reviewed key and supporting information from previous hazard assessments as
well as reasonably available information on 1-BP's human health hazards. These data sources5
included published and non-published data sources, including key and supporting studies identified
in and evaluated in the t Risk Assessment (U.S. EPA. 2016c). EPA relied heavily on the
2l aft Risk Assessment (U.S. EPA. 2016c) to inform hazard characterization. EPA also
screened and evaluated new studies that were published between January 1, 2009 and March 1,
2017).
4 More information about the ECOSAR program can be found at: https://www. epa. gov/tsca-screening-tools/ecological-
structure-activitv-relationships-ecosar-predictive-model
5 1-BP does not have an existing EPA IRIS Assessment.
Page 33 of 486
-------
EPA developed a hazard and dose-response analysis using endpoints observed in inhalation hazard
studies, evaluated the weight of the scientific evidence considering the EPA and National Research
Council (NRC) risk assessment guidance, and selected the points of departure (POD) for non-
cancer endpoints following acute and chronic exposures, and inhalation unit risk and cancer slope
factors for cancer risk estimates. Potential health effects of 1-BP exposure described in the
literature include: liver toxicity, kidney toxicity, reproductive toxicity, developmental toxicity,
neurotoxicity, and cancer. EPA identified non-cancer PODs for acute inhalation and dermal
exposures based on developmental effects {i.e., decreased live litter size, and increases in post-
implantation loss), the most sensitive HECs/dermal HEDs derived for an acute exposure duration
(WIL Research. 2001). The non-cancer PODs for chronic inhalation exposures are based on liver
toxicity, kidney toxicity, reproductive toxicity, developmental toxicity and neurotoxicity. EPA
used the HEC/dermal HED specific to each health effect domain: liver (increased hepatocellular
vacuolization; (WIL Research. 2001)). kidney (increased pelvic mineralization; (WIL Research.
2001)). reproductive system (decreased seminal vesicle weight; (Ichihara et al.. 2000b).
developmental effects (F1 decreased live litter size, F0 post-implantation loss - NLogistic model;
(WIL Research. 2001)). nervous system (decreased traction time; (Honma et al.. 2003). EPA
searched for but did not identify toxicity studies by the dermal route that were adequate for dose-
response assessment. Therefore, dermal candidate values were derived by route-to-route
extrapolation from the inhalation PODs mentioned above. No physiologically based
pharmacokinetic/ pharmacodynamic (PBPK/PD) models that would facilitate route-to-route
extrapolation have been identified. By the criteria presented in EPA's Guidelines for Carcinogen
Risk Assessment (U.S. EPA. 2005a). 1-BP may be considered "Likely to be Carcinogenic in
Humans" based on the positive findings for carcinogenicity in more than one test species, together
with positive findings for the direct reactivity of 1 -BP with DNA and suggestive but inconclusive
evidence for genetic toxicity. In a two-year cancer bioassay with 1-BP exposures viva the
inhalation route (NTP. 2011a). increases in the incidence of skin tumors
(keratoacanthoma/squamous cell carcinomas) in male F344 rats, rare large intestine adenomas in
female F344 rats, and alveolar/bronchiolar adenomas or carcinomas (combined) in female B6C3F1
mice were observed. EPA calculated cancer risk estimates using a linear model and cancer slope
factors based on these endpoints.
Risk Characterization
Environmental Risk: EPA qualitatively considered physical-chemical and environmental fate
properties of 1-BP and determined that exposures of 1-BP to terrestrial species and sediment-
dwelling aquatic species are expected to be low and risks are not expected. EPA calculated a risk
quotient (RQ) by comparing the estimated concentration of 1-BP in surface water resulting from
aquatic releases to the hazard thresholds for aquatic species in order to characterize the risks to
water column-dwelling aquatic organisms. EPA did not identify any exceedances, as all RQ values
for acute and chronic exposure leading to risks are <1. An RQ that does not exceed 1 indicates that
the exposure concentrations of 1-BP are less than the concentrations that would cause an effect to
organisms in the aquatic pathways and risk concerns for these organisms were not identified. The
Page 34 of 486
-------
results of the risk characterization are in Section 4.1, including a table that summarizes the RQs for
risks associated with acute and chronic exposures.
Human Health Risks: For workers and ONUs, EPA estimated potential non-cancer risks resulting
from acute or chronic inhalation exposure using a Margin of Exposure (MOE) approach. EPA also
estimated potential cancer risk from chronic inhalation exposures to 1-BP using inhalation unit risk
slope factors values multiplied by the chronic exposure for each COU. Similarly for dermal
exposure to workers, EPA used the MOE approach and dermal cancer slope factors to estimate
non-cancer and cancer risks, respectively.
For workers, risks for non-cancer effects following acute and chronic inhalation exposures were
indicated under high-end exposure levels for most conditions of use if personal protective
equipment (PPE) was not used. Cancer risks were also identified following both inhalation and
dermal exposure for most conditions of use if PPE was not used. With the use of respiratory
protection, worker exposures were reduced, but some conditions of use continued to present non-
cancer and cancer risks following inhalation exposure under high-end exposure levels even with
PPE (APF = 50). With the use of protective gloves (PF = 5), dermal risks were mitigated for all
conditions of use. EPA's risk estimates for workers are presented in Section 4.2.3 and Section
4.2.5.
For ONUs, risks for non-cancer and cancer effects following acute and chronic exposures were
also indicated for central tendency and high-end inhalation exposure levels for most conditions of
use. Because ONUs do not directly handle 1-BP in the workplace, they are not assumed to use
respiratory protection. ONUs are not assumed to be dermally exposed to 1-BP and dermal risks to
ONUs were not evaluated. EPA's risk estimates for ONUs are presented in Section 4.2.3.
EPA estimated non-cancer risks resulting from acute inhalation exposures for the consumer users
and bystanders. EPA estimated non-cancer risks resulting from acute dermal exposures for the
consumer users. EPA estimated non-cancer risks resulting from chronic inhalation exposures and
cancer risks for bystanders from insulation (off-gassing) of 1-BP following installation of
THERMAX™ rigid board insulation within a residence as described in Section 2.3.2.4. These
exposures were modeled with a range of user intensities, described in detail in Section 2.3.2.1.
EPA assumed that consumer users or bystanders would not use PPE and that all exposures, except
those associated with insulation condition of use, would be acute, rather than chronic in nature.
Risks for developmental effects following acute inhalation exposures were indicated for most
consumer conditions of use for both the consumer users and bystanders under low, medium and
high intensity use conditions. Risks for developmental effects following acute dermal exposures
were indicated for four of eight conditions of use evaluated for dermal exposure for the consumer
users. The insulation (off-gassing) condition of use did not indicate risks for bystanders. EPA's
estimates for consumer user and bystander risks for each consumer condition of use evaluated are
presented in Section 4.2.3 and Section 4.2.4.
For the general population, EPA considered reasonably available physical-chemical properties,
environmental release, and environmental fate information to characterize risk from water,
Page 35 of 486
-------
sediment, and soil. As described further in Section 4.5.2.3, EPA does not expect general population
exposure from contaminated drinking water or groundwater, and therefore did not identify risk for
these pathways.
Uncertainties: Key assumptions and uncertainties in the environmental risk estimation are related
to the quality of the environmental hazard data for 1-BP. Only one environmental hazard study was
identified by EPA and evaluated for data quality. Five studies were available only as European
Chemical Agency (ECHA) summaries in the chemical registration database for 1-BP, but EPA was
not able to obtain the full study reports, so these studies were not utilized in the assessment. In
addition, data on the environmental hazards of 1-BP following chronic exposure were not
identified, so estimates of chronic hazard to environmental receptors were based on extrapolations
from acute toxicity data.
For the human health risk estimation, key assumptions and uncertainties are related to data on
exposure monitoring, exposure model input parameters, and their representativeness for that COU.
One key model assumption is that workers and occupational non-users remain in their respective
work zones, which may result in an overestimate of exposure for workers, and an underestimate for
ONUs. An additional source of uncertainty is the inhalation to dermal route-to-route
extrapolations, which is a source of uncertainty in the risk assessment for dermal cancer and non-
cancer risk estimates. For assessing cancer risks, EPA chose to model the lung tumor results from a
cancer bioassay in mice (selected as the POD considered protective for the other tumor types);
however, there is uncertainty regarding the modeling of these tumor types for humans.
Assumptions and key sources of uncertainty are detailed in Section 4.3.
EPA's assessments, risk estimations, and risk determinations account for uncertainties throughout
the risk evaluation. EPA used reasonably available information, 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. For instance, systematic review was conducted to identify reasonably available
information related to 1-BP hazards and exposures. If no applicable monitoring data were
identified, exposure 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-specific inputs available in literature databases. The
consideration of uncertainties support the Agency's risk determinations, each of which is supported
by substantial evidence, as set forth in detail in later sections of this final risk evaluation.
Potentially Exposed or Susceptible Subpopulations (PESS): 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 Administration, 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
Page 36 of 486
-------
health effects from exposure to a chemical substance or mixture, such as infants, children, pregnant
women, workers, or the elderly."
In developing the risk evaluation, EPA analyzed 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 potentially exposed
groups, EPA considered 1-BP exposures to be higher among workers using 1-BP and ONUs in the
vicinity of 1-BP use than the exposures experienced by the general population, and among
consumers and bystanders associated with the use of consumer products. While it is anticipated
that there may be differential 1-BP metabolism based on lifestage, currently there are no data
available, therefore the impact of this cannot be quantified. Similarly, while it is known that there
may be genetic differences that influence CYP2E1 metabolic capacity, there may also be other
metabolizing enzymes that are functional and impact vulnerability. There is insufficient data to
quantify these differences for risk assessment purposes. See additional discussions in Section 4.4.1.
EPA's unreasonable risk determinations are based on high-end exposure estimates for workers and
high intensity use scenarios for consumers and bystanders in order to capture individuals who are
PESS.
Heterogeneity among humans is an uncertainty associated with extrapolating the derived PODs to
a diverse human population. One component of human variability is toxicokinetic, such as
variations in CYP2E1 and glutathione transferase activity in humans (Arakawa et al.. 2012;
Trafalis et al.. 2010) which are involved in 1-BP metabolism in humans and discussed in Section
3.2.3. EPA did not have chemical-specific information on susceptible subpopulations, or the
distribution of susceptibility in the general population that could be used to adjust the default
intraspecies UFh. As such, EPA used an intraspecies UFh of 10 for the risk assessment based on
default factors for toxicokinetic and toxicodynamic variability.
Aggregate and Sentinel Exposures: Section 2605(b)(4)(F)(ii) of TSCA requires 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. 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)." Exposures to 1-BP were evaluated by inhalation and
dermal routes separately. Inhalation and dermal exposures are assumed to occur simultaneously for
workers and consumers. EPA chose not to employ simple additivity of exposure pathways at this
time within a condition of use due to the lack of a physiologically based pharmacokinetic (PBPK)
model for 1-BP. See additional discussions in Section 4.4.2.
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
as the high-end exposure given the details of the conditions of use and the evaluated exposure
scenarios. In cases where sentinel exposures result in MOEs greater than the benchmark or cancer
risk lower than the benchmark, EPA did no further analysis because sentinel exposures represent
Page 37 of 486
-------
the worst-case scenario. EPA's decision for unreasonable risk are based on high-end exposure
estimates to capture individuals with sentinel exposure.
Unreasonable 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.
The determination does not consider costs or other non-risk factors. In making this determination,
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 environmental exposure under the conditions of use; the population exposed (including any
potentially exposed or susceptible subpopulations, as determined by EPA); 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
unreasonable risk determination is discussed in Section 5.2. The Agency's risk determinations are
supported by substantial evidence, as set forth in detail in later sections of this final risk evaluation.
Unreasonable Risk of Injury to the Environment: The physical-chemical and environmental fate
properties (high volatility, high water solubility and low Log Kow) of 1-BP indicate low potential
for exposure to terrestrial and sediment-dwelling aquatic species. In addition, for all conditions of
use, EPA did not identify any exceedances of benchmarks to aquatic organisms from exposures to
1-BP in surface waters. EPA characterized the environmental risk based on one high quality study,
supplemented with predicted toxicity values for acute and chronic exposure based on the
Ecological Structure Activity Relationships (ECOSAR) Class modeling program. Based on the
risk estimates, the environmental effects of 1-BP, the exposures, physical-chemical properties of
1-BP and consideration of uncertainties, EPA determined that there is no unreasonable risk of
injury to the environment from all conditions of use of 1-BP.
Unreasonable Risks of Injury to Health: EPA's determination of unreasonable risk for specific
conditions of use of 1-BP listed below are based on health risks to workers, ONUs, consumers, or
bystanders from consumer use. For acute exposures, EPA evaluated unreasonable risk of
developmental toxicity based on animal studies {i.e., decreased live litter size and post-
implantation loss) and used the most sensitive endpoint to make the unreasonable risk
determination {i.e., post-implantation loss). For chronic exposures, EPA also based the
unreasonable risk determination also on developmental toxicity; however, EPA evaluated other
non-cancer effects {e.g., additional developmental toxicity, reproductive toxicity, liver toxicity,
kidney toxicity, neurotoxicity). For chronic exposures, EPA also evaluated unreasonable risk of
cancer from skin, intestinal and lung tumors. EPA considered the uncertainties associated with the
reasonably available information to justify the linear cancer dose-response model when compared
to other available models.
Page 38 of 486
-------
Unreasonable Risk of Injury to Health of the General Population: As part of the Problem
Formulation for BP (U.S. EPA. 2018c). EPA found that 1-BP exposures to the general population
may occur from the conditions of use due to releases to air, water or land. Based on the qualitative
assessment described in the Problem Formulation for 1-BP, EPA determined that there is no
unreasonable risk to general population from all conditions of use from drinking water, surface
water, or sediment pathways via the oral and dermal routes. The exposures to general population
via ambient air and disposal pathways falls under the jurisdiction of other environmental statutes
administered by EPA, i.e., CAA and RCRA. As explained in more detail in Section 1.4.2, EPA
believes it is both reasonable and prudent to tailor TSCA risk evaluations when other EPA offices
have expertise and experience to address specific environmental media, rather than attempt to
evaluate and regulate potential exposures and risks from those media under TSCA. EPA believes
that coordinated action on exposure pathways and risks addressed by other EPA-administered
statutes and regulatory programs is consistent with statutory text and legislative history,
particularly as they pertain to TSCA's function as a "gap-filling" statute, and also furthers EPA
aims to efficiently use Agency resources, avoid duplicating efforts taken pursuant to other Agency
programs, and meet the statutory deadline for completing risk evaluations. EPA has therefore
tailored the scope of the risk evaluation for 1-BP using authorities in TSCA section 6(b) and
9(b)(1). EPA did not evaluate risk to the general population from ambient air and disposal
pathways for any conditions of use, and the no unreasonable risk determinations do not account
for exposures to the general population from ambient air and disposal pathways.
Unreasonable Risk of Injury to Health of Workers: EPA evaluated non-cancer effects from acute
and chronic inhalation and dermal occupational exposures and cancer from chronic inhalation and
dermal occupation exposures to determine if there was unreasonable risk of injury to workers'
health. The drivers for EPA's determination of unreasonable risk for non-cancer effects for
workers are developmental effects resulting from acute and chronic inhalation exposure, and
cancer from chronic inhalation exposure. EPA determined an unreasonable risk of injury to
workers of cancer from chronic dermal exposure from one condition of use: the industrial and
commercial use of 1-BP in dry cleaning solvents, spot cleaners and stain removers.
EPA generally assumes compliance with OSHA requirements for protection of workers, including
the implementation of the hierarchy of controls. In support of this assumption, EPA used
reasonably available information indicating that some employers, particularly in the industrial
setting, are providing appropriate engineering, administrative controls, or PPE to their employees
consistent with OSHA requirements. While OSHA has not issued a specific PEL for 1-BP, EPA
assumes some use of PPE due to the hazard alert6 for occupational exposure to 1-BP jointly issued
by OSHA and NIOSH and the Threshold Limit Value™ (TLV™) adopted by the American
Conference of Governmental Industrial Hygienists (ACGIH™). EPA does not have reasonably
available information to support this assumption for each condition of use; however, EPA does not
believe that the Agency must presume, in the absence of such information, a lack of compliance
with existing regulatory programs and practices. Rather, EPA assumes there is compliance with
6 https://www.cdc.gov/niosh/docs/2013-150/pdfs/2013-150.pdf?id= 10.26616/NIOSHPUB2Q13150
Page 39 of 486
-------
worker protection standards unless case-specific facts indicate otherwise, and therefore existing
OSHA regulations for worker protection and hazard communication will result in use of
appropriate PPE in a manner that achieves the stated APF or PF. EPA's decisions for unreasonable
risk to workers are based on high-end exposure estimates, in order to account for the uncertainties
related to whether or not workers are using PPE. EPA believes this is a reasonable and appropriate
approach that accounts for reasonably available information and professional judgement related to
worker protection practices, and addresses uncertainties regarding availability and use of PPE.
For each condition of use of 1-BP, EPA assumes the use of a respirator with an APF of 10 to 50.
Similarly, EPA assumes the use of gloves with PF of 5. However, EPA assumes that for some
conditions of use, the use of respirators is not a standard industry practice, based on best
professional judgement given the burden associated with the use of respirators, including the
expense of the equipment and the necessity of fit-testing and training for proper use. Similarly,
EPA does not assume that as a standard industry practice that workers in dry cleaning facilities use
gloves.
The unreasonable risk determinations reflect the severity of the effects associated with the
occupational exposures to 1-BP and incorporate EPA assumptions of PPE use (respirators with
APF from 10 to 50 and gloves with PF of 5). A full description of EPA's unreasonable risk
determination for each condition of use, including the PPE assumptions, is in Section 5.2.
Unreasonable Risk of Injury to Health of Occupational Non-Users (ONUs): ONUs are workers
who do not directly handle 1-BP but perform work in an area where 1-BP is present. EPA
evaluated non-cancer effects to ONUs from acute and chronic inhalation occupational exposures
and cancer from chronic inhalation occupational exposures to determine if there was unreasonable
risk of injury to ONUs' health. The unreasonable risk determinations reflect the severity of the
effects associated with the occupational exposures to 1-BP and the assumed absence of PPE for
ONUs, since ONUs do not directly handle the chemical and are instead doing other tasks in the
vicinity of 1-BP use. Non-cancer effects and cancer from dermal occupational exposures to ONUs
were not evaluated because ONUs are not dermally exposed to 1-BP. For inhalation exposures,
EPA, where possible, estimated ONUs' exposures and described the risks separately from workers
directly exposed. When the difference between ONUs' exposures and workers' exposures cannot
be quantified, EPA assumed that ONUs' inhalation exposures are lower than inhalation exposures
for workers directly handling the chemical substance. A full description of EPA's unreasonable
risk determination for each condition of use is in Section 5.2.
Unreasonable Risk of Injury to Health of Consumers: EPA evaluated non-cancer effects to
consumers from acute inhalation and dermal exposures to determine if there was unreasonable risk
of injury to consumers' health. A full description of EPA's unreasonable risk determination for
each condition of use is in Section 5.2.
Unreasonable Risk of Injury to Health of Bystanders (from Consumer Uses): EPA evaluated non-
cancer effects to bystanders from acute inhalation exposures to determine if there was
unreasonable risk of injury to bystanders' health. For one consumer condition of use (use of 1-BP
in insulation), EPA also evaluated non-cancer effects and cancer from chronic inhalation
Page 40 of 486
-------
exposures. EPA did not evaluate non-cancer effects from dermal exposures to bystanders because
bystanders are not dermally exposed to 1-BP. A full description of EPA's unreasonable risk
determination for each condition of use is in Section 5.2.
Summary of Unreasonable Risk Determinations:
In conducting risk evaluations, "EPA will determine whether the chemical substance presents an
unreasonable risk of injury to health or the environment under each condition of use within the
scope of the risk evaluation..." 40 CFR 702.47. Under EPA's implementing regulations, "[a]
determination by EPA that the chemical substance, under one or more of the conditions of use
within the scope of the risk evaluation, does not present an unreasonable risk of injury to health or
the environment will be issued by order and considered to be a final Agency action, effective on
the date of issuance of the order." 40 CFR 702.49(d).
EPA has determined that the following conditions of use of 1-BP do not present an unreasonable
risk of injury to health or the environment. These determinations are considered final agency action
and are being issued by order pursuant to TSCA section 6(i)(l). The details of these determinations
are presented in Section 5.2, and the TSCA section 6(i)(l) order is contained in Section 5.4.1 of
this final risk evaluation.
Conditions of Use that Do Not Present an Unreasonable Risk
• Manufacturing (domestic manufacturing)
• Manufacturing (import)
• Processing: as a reactant
• Processing: incorporation into articles
• Processing: repackaging
• Processing: recycling
• Distribution in commerce
• Commercial and consumer uses of building/construction materials (insulation)
• Disposal
EPA has determined that the following conditions of use of 1-BP present an unreasonable risk of
injury. EPA will initiate TSCA section 6(a) risk management actions on these conditions of use as
required under TSCA section 6(c)(1). Pursuant to TSCA section 6(i)(2), the unreasonable risk
determinations for these conditions of use are not considered final agency action. The details of
these determinations are in Section 5.2.
Processing that Present an Unreasonable Risk
• Incorporation into a formulation, mixture or reaction product
Industrial and Commercial Uses that Present an Unreasonable Risk
• Industrial and commercial use as solvent for cleaning and degreasing in vapor degreaser (batch
vapor degreaser - open-top, inline vapor degreaser)
Page 41 of 486
-------
Industrial and Commercial Uses that Present an Unreasonable Risk
• Industrial and commercial use as solvent for cleaning and degreasing in vapor degreaser (batch
vapor degreaser - closed-loop)
• Industrial and commercial use as solvent for cleaning and degreasing in cold cleaners
• Industrial and commercial use as solvent in aerosol spray degreaser/cleaner
• Industrial and commercial use in adhesives and sealants
• Industrial and commercial use in dry cleaning solvents, spot cleaners and stain removers
• Industrial and commercial use in liquid cleaners (e.g., coin and scissor cleaner) and liquid
spray/aerosol cleaners
• Other industrial and commercial uses: arts, crafts, hobby materials (adhesive accelerant);
automotive care products (engine degreaser, brake cleaner, refrigerant flush); anti-adhesive
agents (mold cleaning and release product); electronic and electronic products and metal
products; functional fluids (close/open-systems) - refrigerant/cutting oils; asphalt extraction;
laboratory chemicals; and temperature indicator - coatings
Consumer Uses that Present an Unreasonable Risk
• Consumer use as solvent in aerosol spray degreasers/cleaners
• Consumer use in spot cleaners and stain removers
• Consumer use in liquid cleaners (e.g., coin and scissor cleaners)
• Consumer use in liquid spray/aerosol cleaners
• Consumer use in arts, crafts, hobby materials (adhesive accelerant)
• Consumer use in automotive care products (refrigerant flush)
• Consumer use in anti-adhesive agents (mold cleaning and release product)
Page 42 of 486
-------
1 INTRODUCTION
This document is the final risk evaluation for 1-bromopropane (1-BP) 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 (TSCA), the Nation's primary
chemicals management law, on June 22, 2016.
The Agency published the Scope of the Risk Evaluation for 1-BP (U.S. EPA. 2017d) in June 2017,
and the Problem Formulation in June 2018 (U.S. EPA. 2018c). which represented the analytical
phase of risk evaluation in which "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 (U.S. EPA. 2018c) for 1-BP and has considered
the comments specific to 1-BP, as well as more general comments regarding EPA's chemical risk
evaluation approach for developing the risk evaluations for the first 10 chemicals EPA is
evaluating. The Problem Formulation identified conditions of use within the scope of the risk
evaluation and presented three conceptual models and an analysis plan. Based on EPA's analysis
of the conditions of use, physical-chemical and fate properties, environmental releases, and
exposure pathways, the preliminary conclusions of the Problem Formulation were that further
analysis of exposure pathways, to workers and consumers was necessary in this risk evaluation;
and that further analysis for environmental release pathways leading to surface water, sediment, or
land-applied biosolid exposures to ecological receptors was not necessary in this risk evaluation.
EPA subsequently published a draft risk evaluation for 1-BP in August 2019 and has taken public
and peer review comments. The conclusions, findings, and determinations in this final 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 TSCA Section 7.
As per EPA's final Risk Evaluation Rule, Procedures for Chemical Risk Evaluation Under the
Amended Toxic Substances Control Act (82 FR 33726). the risk evaluation was subject to both
public comment and peer review, which are distinct but related processes. EPA provided 60 days
for public comment on all aspects of the draft risk evaluation, including the submission of any
additional information that might be relevant to the science underlying the risk evaluation. This
satisfies TSCA section 6(b)(4)(H), which requires EPA to provide public notice and an opportunity
for comment on a draft risk evaluation prior to publishing a final risk evaluation.
Peer review was conducted in accordance with EPA's regulatory procedures for chemical risk
evaluations, including using the EPA Peer Review Handbook and other methods consistent with
section 26 of TSCA (See 40 CFR 702.45). As explained in the Risk Evaluation Rule (82 FR 33726
(July 20, 2017)), the purpose of peer review is for the independent review of the science underlying
the risk assessment. 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.
Page 43 of 486
-------
As EPA explained in the Risk Evaluation Rule (82 FR 33726 (July 20, 2017)), it is important for
peer reviewers to consider how the underlying risk evaluation analyses fit together to produce an
integrated risk characterization, which forms the basis of an unreasonable risk determination. EPA
believes peer reviewers will be most effective in this role if they received the benefit of public
comments on draft risk evaluations prior to peer review. For this reason, and consistent with
standard Agency practice, the public comment period preceded peer review on the draft risk
evaluation. EPA responded to public and peer review comments received on the Draft Risk
Evaluation and explained changes made to the draft risk evaluation for 1-BP in response to those
comments in this final risk evaluation and the associated response to comments document.
EPA also solicited input on the first 10 chemicals as it developed use dossiers, Scope Documents,
and Problem Formulations. At each step, EPA has 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 received 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 (U.S. EPA. 2018c) of 1-BP.
In this final risk evaluation, Section 1 presents the basic physical-chemical properties of 1-BP, as
well as a background on uses, regulatory history, conditions of use and conceptual models, with
particular emphasis on any changes since the publication of the Draft Risk Evaluation. Section 1
also includes a discussion of the systematic review process utilized in this risk evaluation. Section
2 provides the analysis and discussion of the exposures, both human and environmental, that can
be expected based on the conditions of use for 1-BP. Section 3 discusses environmental and human
health hazards of 1-BP. Risk characterization is presented in Section 4, which integrates and
assesses the best available science and "reasonably available information"7 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 any uncertainties and how they impact the risk evaluation. In
Section 4.5.2.3, the agency presents the risk determination of whether risks posed by the chemical
substance under the conditions of use are "unreasonable" as required under TSCA (15 U.S.C.
2605(b)(4)).
1.1 Physical and Chemical Properties
1-BP is a colorless liquid with a sweet odor. It is a brominated hydrocarbon that is slightly soluble
in water. 1-BP is a volatile organic compound (VOC) that exhibits high volatility, a low boiling
7 "Reasonably available information means information that EPA possesses or can reasonably generate, obtain, and
synthesize for use in risk evaluations, considering the deadlines specified in TSCA section 6(b)(4)(G) for completing
such evaluation. Information that meets the terms of the preceding sentence is reasonably available information
whether or not the information is confidential business information, that is protected from public disclosure under
TSCA Section 14."
Page 44 of 486
-------
point, low flammability and no explosivity. Figure 1-1 presents the chemical structure and Table
1-1 summarizes the physical-chemical properties of 1-BP.
Br
CH
Figure 1-1. Chemical Structure of 1-Bromopropane
Table 1-1. Physical-Chemical Properties of 1-BP
Propi'i'M
\ illllO •'
Reference
Molecular formula
C3H7Br
O'Neil (2013)
Molecular weight
122.99
(Weil (2013)
Physical form
Colorless liquid; sweet hydrocarbon
odor
O'Neil (2013)
Melting point
-110°C
O'Neil (2013)
Boiling point
71°C at 760 mmHg
O'Neil (2013)
Density
1.353 g/cm3 at 20°C
O'Neil (2013)
Vapor pressure
110.8 mmHg (14.77 kPa) at 20°C
Boublik et al. (1984)
Vapor density
4.25 (relative to air)
Pattv et al. (1963)
Water solubility
2.450 g/L at 20°C
Yalkowskv et al. (2010)
Octanol/water partition coefficient
(Log Kow)
2.10
Hansch (1995)
Henry's Law constant
7.3xl0 3 atm-m3/mole (calculated)
U.S. EPA (2012c)
Flash point
22°C
O'Neil (2013)
Autoflammability
490°C
NFPA (2010)
Viscosity
0.489 mPa s at 25°C
Havnes and Lide (2010)
Refractive index
1.4341
O'Neil (2013)
Dielectric constant
8.09 at 20°C
Havnes and Lide (2010)
a Measured unless otherwise noted.
Page 45 of 486
-------
1.2 Uses and Production Volume
The information on the conditions of use is grouped according to Chemical Data Reporting (CDR)
processing codes and use categories (including functional use codes for industrial uses and product
categories for industrial, commercial and consumer uses), in combination with other data sources
(e.g., published literature and consultation with stakeholders), to provide an overview of conditions
of use. EPA notes that some subcategories of use may be grouped under multiple CDR categories.
Use categories include the following: "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 (U.S. EPA. 2016a).
CDR, information from commenters, and types of available products show that the primary use of
1-BP is degreasing. The exact use volumes associated with degreasing is CBI8 in the 2016 CDR
(U.S. EPA. 2016a). EPA evaluated activities resulting in exposures associated with distribution in
commerce (e.g., loading, unloading) throughout the various lifecycle stages and conditions of use
(e.g., manufacturing, processing, industrial use, consumer use, disposal) rather than as a single
distribution scenario. EPA expects that some commercial products containing 1-BP are also
available for purchase by consumers, such that many products are used in both commercial and
consumer applications/scenarios.
The 2016 CDR reporting data on the production volume for 1-BP are provided in Table 1-2 and
come from EPA's CDR database (U.S. EPA. 2016a). This information has not changed from that
provided in the Scope Document (EPA-HQ-OPPT-2016-0741-0049).
Table 1-2. Production Volume of 1-BP in CDR Reporting Period (2012 to 2015)a
Reporting Yesir
2012
2013
2014
2015
Total Aggregate
Production Volume (lbs)
18,800,000
24,000,000
18,500,000
25,900,000
a The CDR data for the 2016 reporting period is available via ChemView (https://chemview.epa.gov/chemview)
(U.S. EPA. 2016a'). Because of the CBI substantiation process required by amended TSCA, the CDR data available
in the Scope Document (EPA-HO-OPPT-2016-0741 -00491 is more specific than currently in ChemView.
According to data collected in EPA's 2016 Chemical Data Reporting (CDR) Rule, 25.9 million
pounds of 1-BP were manufactured in or imported into the United States in 2015 (U.S. EPA.
8 EPA does have access to and does review all CBI information in this process. EPA has also reviewed all CBI claims
referred to in this risk evaluation, and these claims have been substantiated and approved by EPA.
Page 46 of 486
-------
2016a). Data publicly reported indicate that there are two domestic manufacturers and eight
importers of 1-BP in the United States.
Total production volume (domestic manufacture plus import) of 1-BP has increased from 2012 to
2015, as can be seen in Table 1-2 (U.S. EPA. 2016a). 1-BP's volume has increased because it has
been an alternative to ozone-depleting substances and chlorinated solvents. Import volumes for
1-BP reported to the 2016 CDR are between 10 million and 25 million pounds per year (U.S. EPA.
2016a).
1.3 Regulatory and Assessment History
EPA conducted a search of existing domestic and international laws, regulations and assessments
pertaining to 1-BP. EPA compiled a regulatory summary from federal, state, international and
other government sources, as cited in Appendix A.
Federal Laws and Regulations
1-BP is subject to federal statutes or regulations, in addition to TSCA, that are implemented by
other offices within EPA and/or other federal agencies/departments. A summary of federal laws,
regulations and implementing authorities is provided in Appendix A.l.
State Laws and Regulations
1-BP is subject to state statutes or regulations implemented by state agencies or departments. A
summary of state laws, regulations and implementing authorities is provided in Appendix A.2.
Laws and Regulations in Other Countries and International Treaties or Agreements
1-BP 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.
Assessment History
EPA has identified assessments conducted by other EPA Programs and other organizations (see
Table 1-3). Depending on the source, these assessments may include information on conditions of
use, hazards, exposures, and potentially exposed or susceptible subpopulations. EPA found no
additional assessments beyond those listed in the Scope Document (Scope Document; EPA-HQ-
OPPT-2016-0741 -0049) and the Problem Formulation document (U.S. EPA. 2018c).
In addition to using this information, EPA conducted a full review of the relevant data and
information collected in the initial comprehensive search (see 1-Bromopropane (CASRN106-94-5)
Bibliography: Supplemental File for the TSCA Scope Document. EPA-HQ-QPPT-2016-0741-
0048) using the literature search and screening strategies documented in the Strategy for
Conducting Literature Searches for 1-Bromopropane (1-BP): Supplemental Document to the TSCA
Scope Document (U.S. EPA. 2017e). Thus, EPA considered data and information that has been
made available since these assessments were conducted.
Page 47 of 486
-------
Table 1-3. Assessment History of 1-BP
Authoring Organi/alion
Assessment
EPA Assessments
Office of Chemical Safety and Pollution Prevention
(OCSPP)/Office of Pollution Prevention and Toxics
(OPPT)
TSCA work plan chemical risk assessment: Peer review
draft 1-bromopropane: (n-Propyl bromide) spray adhesives,
drv cleanine. and desreasins uses CASRN: 106-94-5 12016
Draft Risk Assessment (U.S. EPA. 2016c)l
Office of Air Quality Planning and Standards (OAQPS)
Draft notice to grant the petition to add 1-BP to the list of
HAPs dittos: //w \v\\. re a u 1 a 0 o n s. eov/document?D=EPA-
HO-OAR-2014-0471-0062)
Other U.S.-Based Organizations
National Institute for Occupational Safety and Health
(NIOSH)
Criteria for a Recommended Standard: Occupational
Exposure to l-Bromoorooane (2016)
Agency for Toxic Substances and Disease Registry
(ATSDR)
Toxicoloeical Profile for l-Bromoorooane (2017)
1.4 Scope of the Evaluation
1.4.1 Conditions of Use Included in the Risk Evaluation
TSCA § 3(4) defines the conditions of use as "the circumstances, as determined by the
Administrator, under which a chemical substance is intended, known, or reasonably foreseen to be
manufactured, processed, distributed in commerce, used, or disposed of." Conditions of use have
not changed since the issuance of the 1-BP Problem Formulation (U.S. EPA. 2018c) on June 11,
2018; thus, the conditions of use described in the 1-BP Problem Formulation, and reproduced
below in Table 1-4, remain the same. No additional information was received by EPA following
the publication of the problem formulation that would require updating the conditions of use (Table
2-2) or the life cycle diagram as presented in the June 2018 Problem Formulation (U.S. EPA.
2018c).
The life cycle diagram in Figure 1-2 depicts the conditions of use that are within the scope of the
risk evaluation during various life cycle stages including manufacturing, processing, use
(industrial, commercial, consumer), distribution and disposal. The production volumes shown are
for reporting year 2015 from the 2016 CDR reporting period (U.S. EPA. 2016a). EPA will evaluate
activities resulting in exposures associated with distribution in commerce (e.g., loading, unloading)
throughout the various lifecycle stages and conditions of use (e.g., manufacturing, processing,
industrial use, consumer use, disposal) rather than as a separate distribution scenario.
EPA has not exercised its authority in TSCA section 6(b)(4)(D) to exclude any 1-BP conditions of
use from the scope of the 1-BP risk evaluation.
Page 48 of 486
-------
Table 1-4. Categories and Subcategories of Conditions of Use Included in the Scope of the Risk
Evaluation
Life Cycle Stage
Category a
Subcategory b
References
Manufacture
Domestic manufacture
Domestic manufacture
U.S. EPA (2016a)
Import
Import
U.S. EPA (2016a)
Processing
Processing as a reactant
Intermediate in all other basic
inorganic chemical
manufacturing, all other basic
organic chemical
manufacturing, and pesticide,
fertilizer and other agricultural
chemical manufacturing
U.S. EPA (2016a)
Processing - incorporating
into formulation, mixture
or reaction product
Solvents for cleaning or
degreasing in manufacturing of:
- all other chemical product
and preparation
- computer and electronic
product
- electrical equipment,
appliance and component
- soap, cleaning compound
and toilet preparation
- services
U.S. EPA (2016a)
Processing - incorporating
into articles
Solvents (which become part of
product formulation or mixture)
in construction
U.S. EPA (2016a): Public Comment.
EPA-HO-OPPT-2016-0741 -0017
Processing
Repackaging
Solvent for cleaning or
degreasing in all other basic
organic chemical
manufacturing
U.S. EPA (2016a)
Recycling
Recycling
U.S. EPA (2016a): Use Document. EPA-
HO-OPPT-2016-0741 -0003
Distribution in
commerce
Distribution
Distribution
U.S. EPA (2016a): Use Document. EPA-
HO-OPPT-2016-0741 -0003
Page 49 of 486
-------
Table 1-4. Categories and Subcategories of Conditions of Use Included in the Scope of the Risk
Evaluation
Life Cycle Stage
Category a
Subcategory b
References
Industrial/
commercial use
Solvent (for cleaning or
degreasing)
Batch vapor degreaser (e.g.,
open-top, closed-loop)
U.S. EPA (2016c): Public Comment.
EPA-HO-OPPT-2016-0741-0014;
Public Comment. EPA-HO-OPPT-2016-
0741-0015; Public Comment. EPA-HO-
OPPT-2016-0741-0016
In-line vapor degreaser (e.g.,
conveyorized, web cleaner)
Kanessbers and Kanessbers (2011);
Public Comment. EPA-HO-OPPT-2016-
0741-0014; Public Comment. EPA-HO-
OPPT-2016-0741-0016
Cold cleaner
U.S. EPA (2016c); Public Comment.
EPA-HO-OPPT-2016-0741-0016
Aerosol spray degreaser/cleaner
U.S. EPA (2016c); Public Comment.
EPA-HO-OPPT-2016-0741-0016;
Public Comment. EPA-HO-OPPT-2016-
0741-0018; Public Comment. EPA-HO-
OPPT-2016-0741-0020
Adhesives and sealants
Adhesive chemicals - spray
adhesive for foam cushion
manufacturing and other uses
U.S. EPA (2016c); Public Comment.
EPA-HO-OPPT-2016-0741-0016
Industrial/
commercial/use
Cleaning and furniture care
products
Dry cleaning solvent
U.S. EPA (2016c); Public Comment.
EPA-HO-OPPT-2016-0741 -0005;
Public Comment. EPA-HO-OPPT-2016-
0741-0016
Spot cleaner, stain remover
U.S. EPA (2016c); Public Comment.
EPA-HO-OPPT-2016-0741-0016;
Public Comment. EPA-HO-OPPT-2016-
0741-0022
Liquid cleaner (e.g., coin and
scissor cleaner)
Use Document. EPA-HO-OPPT-2016-
0741-0003
Liquid spray/aerosol cleaner
Use Document. EPA-HO-OPPT-2016-
0741-0003
Page 50 of 486
-------
Table 1-4. Categories and Subcategories of Conditions of Use Included in the Scope of the Risk
Evaluation
Life Cycle Stage
Category a
Subcategory b
References
Industrial/
commercial/use
Other uses
Arts, crafts and hobby materials
- adhesive accelerant
U.S. EPA (2016c)
(continued)
Automotive care products -
engine degreaser, brake cleaner
Use Document. EPA-HO-OPPT-2016-
0741-0003
Anti-adhesive agents - mold
cleaning and release product
U.S. EPA (2016c): Public Comment.
EPA-HO-OPPT-2016-0741-0014;
Public Comment. EPA-HO-OPPT-2016-
0741-0015; Public Comment. EPA-HO-
OPPT-2016-0741-0016; Public
Comment. EPA-HO-OPPT-2016-0741 -
0018
Building/construction materials
not covered elsewhere -
insulation
Use Document. EPA-HO-OPPT-2016-
0741-0003; Public Comment. EPA-HO-
OPPT-2016-0741-0027
Electronic and electronic
products and metal products
U.S. EPA (2016a); Public Comment.
EPA-HO-OPPT-2016-0741-0016;
Public Comment. EPA-HO-OPPT-2016-
0741-0024
Functional fluids (closed
systems) - refrigerant
Use Document. EPA-HO-OPPT-2016-
0741-0003
Functional fluids (open system)
- cutting oils
Use Document. EPA-HO-OPPT-2016-
0741-0003; Public Comment. EPA-HO-
OPPT-2016-0741-0014
Other - asphalt extraction
Use Document. EPA-HO-OPPT-2016-
0741-0003; Public Comment. EPA-HO-
OPPT-2016-0741-0016
Other - laboratory chemicals0
Use Document. EPA-HO-OPPT-2016-
0741-0003; Public Comment. EPA-HO-
2016-0741-0059
Temperature indicator-
coatings
Use Document. EPA-HO-OPPT-2016-
0741-0003; Public Comment. EPA-HO-
OPPT-2016-0741-0014; Public
Comment. EPA-HO-OPPT-2016-0741 -
0016
Consumer uses
Solvent (for cleaning or
degreasing)
Aerosol spray degreaser/cleaner
U.S. EPA (2016c);
Page 51 of 486
-------
Table 1-4. Categories and Subcategories of Conditions of Use Included in the Scope of the Risk
Evaluation
Life Cycle Stage
Category a
Subcategory b
References
Cleaning and furniture care
products
Spot cleaner, stain remover
U.S. EPA (2016c): Public Comment.
EPA-HO-OPPT-2016-0741 -0022
Liquid cleaner (e.g., coin and
scissor cleaner)
Use Document. EPA-HO-OPPT-2016-
0741-0003
Liquid spray/aerosol cleaner
Use Document. EPA-HO-OPPT-2016-
0741-0003
Consumer uses
(continued)
Other uses
Arts, crafts and hobby materials
- adhesive accelerant
U.S. EPA (2016c)
Automotive care products -
refrigerant flush
U.S. EPA (2016c)
Anti-adhesive agents - mold
cleaning and release product
U.S. EPA (2016c)
Building/construction materials
not covered elsewhere -
insulation
Use Document. EPA-HO-OPPT-2016-
0741-0003; Public Comment. EPA-HO-
OPPT-2016-0741-0027
Disposal
(Manufacturing,
Processing, Use)
Disposal
Municipal waste incinerator
2016 TRI Data (updated October 2017)
U.S. EPA (2017f)
Off-site waste transfer
aThese categories of conditions of use appear in the Life Cycle Diagram, reflect CDR codes, and broadly represent
conditions of use of 1-BP in industrial and/or commercial settings.
bThese subcategories reflect more specific uses of 1-BP.
0 "Other - laboratory chemicals" was changed from "Temperature indicator - laboratory chemicals" since the problem
formulation because other uses of 1-BP as a laboratory chemical were identified.
Page 52 of 486
-------
MFG/IMPORT
PROCESSING
INDUSTRIAL, COMMERCIAL, CONSUMER USES3
RELEASES and WASTE DISPOSAL
Manufacture
(Includes Import)
(25.8 million lbs)
Processing as Reactant
(Volume CBI)
Incorporated into
Formulation, Mixture,
or Reaction Product
(>1.31 million lbs)
Incorporated into
Article
(Volume CBI)
Repackaging
(>88,100 lbs)
Recycling
Solventsfor Cleaning and
Degreasing
(Volume CBI)
e.g., vapor degreaser, cold cleaner,
aerosol degreaser
Adhesivesand Sealants
(Volume CBI)
e.g., spray adhesive, aerosol spray
adhesive
Cleaning and Furniture Care
Products
(714,000 lbs)
e.g., dry cleaning,spotcleaning,
aerosol cleanerand degreaser, aerosol
spot remover, non-aerosol cleaner
Other Uses
e.g., lubricant,insulation,paintable
mold releaseproduct, refrigerant flush
Disposal
See Figure 1-5 for Environmental
Releases and Wastes
~ Manufacturing (includes import)
~ Processing
~
Figure 1-2. 1-BP Life Cycle Diagram
1 See Table 1-4 for additional uses not mentioned specifically in this diagram.
Page 53 of 486
-------
1.4.2 Exposure Pathways and Risks Addressed by other EPA Administered Statutes
In its TSCA section 6(b) risk evaluations, EPA is coordinating action on certain exposure pathways
and risks falling under the jurisdiction of other EPA-administered statutes or regulatory programs.
More specifically, EPA is exercising its TSCA authorities to tailor the scope of its risk evaluations,
rather than focusing on environmental exposure pathways addressed under other EPA-administered
statutes or regulatory programs or risks that could be eliminated or reduced to a sufficient extent by
actions taken under other EPA-administered laws. EPA considers this approach to be a reasonable
exercise of the Agency's TSCA authorities, which include:
• TSCA section 6(b)(4)(D): "The Administrator shall, not later than 6 months after the
initiation of a risk evaluation, publish the scope of the risk evaluation to be conducted,
including the hazards, exposures, conditions of use, and the potentially exposed or
susceptible subpopulations the Administrator expects to consider... "
• TSCA section 9(b)(1): "The Administrator shall coordinate actions taken under this chapter
with actions taken under other Federal laws administered in whole or in part by the
Administrator. If the Administrator determines that a risk to health or the environment
associated with a chemical substance or mixture could be eliminated or reduced to a
sufficient extent by actions taken under the authorities contained in such other Federal laws,
the Administrator shall use such authorities to protect against such risk unless the
Administrator determines, in the Administrator's discretion, that it is in the public interest
to protect against such risk by actions taken under this chapter."
• TSCA section 9(e): "...[I]f the Administrator obtains information related to exposures or
releases of a chemical substance or mixture that may be prevented or reduced under another
Federal law, including a law not administered by the Administrator, the Administrator shall
make such information available to the relevant Federal agency or office of the
Environmental Protection Agency."
• TSCA section 2(c): "It is the intent of Congress that the Administrator shall carry out this
chapter in a reasonable and prudent manner, and that the Administrator shall consider the
environmental, economic, and social impact of any action the Administrator takes or
proposes as provided under this chapter."
• TSCA section 18(d)(1): "Nothing in this chapter, nor any amendment made by the Frank R.
Lautenberg Chemical Safety for the 21st Century Act, nor any rule, standard of
performance, risk evaluation, or scientific assessment implemented pursuant to this chapter,
shall affect the right of a State or a political subdivision of a State to adopt or enforce any
rule, standard of performance, risk evaluation, scientific assessment, or any other protection
for public health or the environment that— (i) is adopted or authorized under the authority
of any other Federal law or adopted to satisfy or obtain authorization or approval under any
other Federal law..."
Page 54 of 486
-------
TSCA authorities supporting tailored risk evaluations and intra-agencv referrals
TSCA section 6(b)(4)(D)
TSCA section 6(b)(4)(D) requires EPA, in developing the scope of a risk evaluation, to identify the
hazards, exposures, conditions of use, and potentially exposed or susceptible subpopulations the
Agency "expects to consider" in a risk evaluation. This language suggests that EPA is not required
to consider all conditions of use, hazards, or exposure pathways in risk evaluations. As EPA
explained in the "Procedures for Chemical Risk Evaluation Under the Amended Toxic Substances
Control Act" ("Risk Evaluation Rule"), "EPA may, on a case-by-case basis, exclude certain
activities that EPA has determined to be conditions of use in order to focus its analytical efforts on
those exposures that are likely to present the greatest concern, and consequently merit an
unreasonable risk determination." 82 FR 33726, 33729 (July 20, 2017).
In the Problem Formulation documents for many of the first 10 chemicals undergoing risk
evaluation, EPA applied the same authority and rationale to certain exposure pathways, explaining
that "EPA is planning to exercise its discretion under TSCA 6(b)(4)(D) to focus its analytical
efforts on exposures that are likely to present the greatest concern and consequently merit a risk
evaluation under TSCA, by excluding, on a case-by-case basis, certain exposure pathways that fall
under the jurisdiction of other EPA-administered statutes." The approach discussed in the Risk
Evaluation Rule and applied in the Problem Formulation documents is informed by the legislative
history of the amended TSCA, which supports the Agency's exercise of discretion to focus the risk
evaluation on areas that raise the greatest potential for risk. See June 7, 2016 Cong. Rec., S3519-
S3520. Consistent with the approach articulated in the Problem Formulation documents, and as
described in more detail below, EPA is exercising its authority under TSCA to tailor the scope of
exposures evaluated in TSCA risk evaluations, rather than focusing on environmental exposure
pathways addressed under other EPA-administered, media-specific statutes and regulatory
programs.
TSCA section 9(b)(1)
In addition to TSCA section 6(b)(4)(D), the Agency also has discretionary authority under the first
sentence of TSCA section 9(b)(1) to "coordinate actions taken under [TSCA] with actions taken
under other Federal laws administered in whole or in part by the Administrator." This broad,
freestanding authority provides for intra-agency coordination and cooperation on a range of
"actions." In EPA's view, the phrase "actions taken under [TSCA]" in the first sentence of section
9(b)(1) is reasonably read to encompass more than just risk management actions, and to include
actions taken during risk evaluation as well. More specifically, the authority to coordinate intra-
agency actions exists regardless of whether the Administrator has first made a definitive finding of
risk, formally determined that such risk could be eliminated or reduced to a sufficient extent by
actions taken under authorities in other EPA-administered Federal laws, and/or made any
associated finding as to whether it is in the public interest to protect against such risk by actions
taken under TSCA. TSCA section 9(b)(1) therefore provides EPA authority to coordinate actions
with other EPA offices without ever making a risk finding or following an identification of risk.
This includes coordination on tailoring the scope of TSCA risk evaluations to focus on areas of
Page 55 of 486
-------
greatest concern rather than exposure pathways addressed by other EPA-administered statutes and
regulatory programs, which does not involve a risk determination or public interest finding under
TSCA section 9(b)(2).
In a narrower application of the broad authority provided by the first sentence of TSCA section
9(b)(1), the remaining provisions of section 9(b)(1) provide EPA authority to identify risks and
refer certain of those risks for action by other EPA offices. Under the second sentence of section
9(b)(1), "[i]f the Administrator determines that a risk to health or the environment associated with
a chemical substance or mixture could be eliminated or reduced to a sufficient extent by actions
taken under the authorities contained in such other Federal laws, the Administrator shall use such
authorities to protect against such risk unless the Administrator determines, in the Administrator's
discretion, that it is in the public interest to protect against such risk by actions taken under
[TSCA]." Coordination of intra-agency action on risks under TSCA section 9(b)(1) therefore
entails both an identification of risk, and a referral of any risk that could be eliminated or reduced
to a sufficient extent under other EPA-administered laws to the EPA office(s) responsible for
implementing those laws (absent a finding that it is in the public interest to protect against the risk
by actions taken under TSCA).
Risk may be identified by OPPT or another EPA office, and the form of the identification may
vary. For instance, OPPT may find that one or more conditions of use for a chemical substance
present(s) a risk to human or ecological receptors through specific exposure routes and/or
pathways. This could involve a quantitative or qualitative assessment of risk based on reasonably
available information (which might include, e.g., findings or statements by other EPA offices or
other federal agencies). Alternatively, risk could be identified by another EPA office. For example,
another EPA office administering non-TSCA authorities may have sufficient monitoring or
modeling data to indicate that a particular condition of use presents risk to certain human or
ecological receptors, based on expected hazards and exposures. This risk finding could be
informed by information made available to the relevant office under TSCA section 9(e), which
supports cooperative actions through coordinated information-sharing.
Following an identification of risk, EPA would determine if that risk could be eliminated or
reduced to a sufficient extent by actions taken under authorities in other EPA-administered laws. If
so, TSCA requires EPA to "use such authorities to protect against such risk," unless EPA
determines that it is in the public interest to protect against that risk by actions taken under TSCA.
In some instances, EPA may find that a risk could be sufficiently reduced or eliminated by future
action taken under non-TSCA authority. This might include, e.g., action taken under the authority
of the Safe Drinking Water Act to address risk to the general population from a chemical substance
in drinking water, particularly if the Office of Water has taken preliminary steps such as listing the
subject chemical substance on the Contaminant Candidate List. This sort of risk finding and
referral could occur during the risk evaluation process, thereby enabling EPA to use a more
relevant and appropriate authority administered by another EPA office to protect against hazards or
exposures to affected receptors.
Page 56 of 486
-------
Legislative history on TSCA section 9(b)(1) supports both broad coordination on current intra-
agency actions, and narrower coordination when risk is identified and referred to another EPA
office for action. A Conference Report from the time of TSCA's passage explained that section 9 is
intended "to assure that overlapping or duplicative regulation is avoided while attempting to
provide for the greatest possible measure of protection to health and the environment." S. Rep. No.
94-1302 at 84. See also H. Rep. No. 114-176 at 28 (stating that the 2016 TSCA amendments
"reinforce TSCA's original purpose of filling gaps in Federal law," and citing new language in
section 9(b)(2) intended "to focus the Administrator's exercise of discretion regarding which
statute to apply and to encourage decisions that avoid confusion, complication, and duplication").
Exercising TSCA section 9(b)(1) authority to coordinate on tailoring TSCA risk evaluations is
consistent with this expression of Congressional intent.
Legislative history also supports a reading of section 9(b)(1) under which EPA coordinates intra-
agency action, including information-sharing under TSCA section 9(e), and the appropriately-
positioned EPA office is responsible for the identification of risk and actions to protect against
such risks. See, e.g., Senate Report 114-67, 2016 Cong. Rec. S3522 (under TSCA section 9, "if the
Administrator finds that disposal of a chemical substance may pose risks that could be prevented or
reduced under the Solid Waste Disposal Act, the Administrator should ensure that the relevant
office of the EPA receives that information"); H. Rep. No. 114-176 at 28, 2016 Cong. Rec. S3522
(under section 9, "if the Administrator determines that a risk to health or the environment
associated with disposal of a chemical substance could be eliminated or reduced to a sufficient
extent under the Solid Waste Disposal Act, the Administrator should use those authorities to
protect against the risk"). Legislative history on section 9(b)(1) therefore supports coordination
with and referral of action to other EPA offices, especially when statutes and associated regulatory
programs administered by those offices could address exposure pathways or risks associated with
conditions of use, hazards, and/or exposure pathways that may otherwise be within the scope of
TSCA risk evaluations.
TSCA sections 2(c) & 18(d)(1)
Finally, TSCA sections 2(c) and 18(d) support coordinated action on exposure pathways and risks
addressed by other EPA-administered statutes and regulatory programs. Section 2(c) directs EPA
to carry out TSCA in a "reasonable and prudent manner" and to consider "the environmental,
economic, and social impact" of its actions under TSCA. Legislative history from around the time
of TSCA's passage indicates that Congress intended EPA to consider the context and take into
account the impacts of each action under TSCA. S. Rep. No. 94-698 at 14 ("the intent of Congress
as stated in this subsection should guide each action the Administrator takes under other sections of
the bill").
Section 18(d)(1) specifies that state actions adopted or authorized under any Federal law are not
preempted by an order of no unreasonable risk issued pursuant to TSCA section 6(i)(l) or a rule to
address unreasonable risk issued under TSCA section 6(a). Thus, even if a risk evaluation were to
address exposures or risks that are otherwise addressed by other federal laws and, for example,
implemented by states, the state laws implementing those federal requirements would not be
Page 57 of 486
-------
preempted. In such a case, both the other federal and state laws, as well as any TSCA section
6(i)(l) order or TSCA section 6(a) rule, would apply to the same issue area. See also TSCA section
18(d)(l)(A)(iii). In legislative history on amended TSCA pertaining to section 18(d), Congress
opined that "[t]his approach is appropriate for the considerable body of law regulating chemical
releases to the environment, such as air and water quality, where the states have traditionally had a
significant regulatory role and often have a uniquely local concern." Sen. Rep. 114-67 at 26.
EPA's careful consideration of whether other EPA-administered authorities are available and more
appropriate for addressing certain exposures and risks is consistent with Congress's intent to
maintain existing federal requirements and the state actions adopted to locally and more
specifically implement those federal requirements, and to carry out TSCA in a reasonable and
prudent manner. EPA believes it is both reasonable and prudent to tailor TSCA risk evaluations in
a manner reflective of expertise and experience exercised by other EPA and State offices to
address specific environmental media, rather than attempt to evaluate and regulate potential
exposures and risks from those media under TSCA. This approach furthers Congressional direction
and EPA aims to efficiently use Agency resources, avoid duplicating efforts taken pursuant to
other Agency and State programs, and meet the statutory deadline for completing risk evaluations.
EPA-administered statutes and regulatory programs that address specific exposure pathways and/or
risks
As referenced in the 1-BP Problem Formulation (U.S. EPA, 2018c). EPA, through its Office of Air
and Radiation (OAR), issued a draft notice of the Agency's rationale for granting the petition to
add 1-BP to the list of HAPs contained in section 112(b)(1) of the Clean Air Act (CAA), 42 U.S.C.
7412. 82 FR 2354 (Jan. 9, 2017). Since publication of the 1-BP Problem Formulation and the
release of the draft 1-BP Risk Evaluation, EPA, through its OAR, issued a final notice to grant the
petition to add 1-BP to the list of HAPs contained in section 112(b)(1) of the CAA, 42 U.S.C.
7412. 85 FR 36851 (June 18, 2020). This will trigger a regulatory process for reducing air
emissions of 1-BP under the C A A, as outlined in the final notice - See 85 FR at 36854. The docket
number for the draft and final OAR notices granting the petition is Docket ID No. EPA-HQ-OAR-
2014-0471.
As a result of the preliminary findings presented by petitioners showing increased cancer risks to
the general population as a result of exposure to 1-BP via ambient air, which is relied upon, in part,
by the OAR in its draft9 and final10 notices to grant the petitions to list 1-BP as a hazardous air
pollutant (HAP), along with other information submitted to the docket11, EPA has identified risk
for purposes of TSCA section 9(b). This finding is not intended to constitute a finding under the
CAA section 1 12. EPA has elected to utilize its TSCA authorities under Section 9(b)(1) to
9 82 Fed. Reg. 2.354 (Januaiy 9, 2017).
10 85 Fed. Reg. 36.851 (June 18, 2020).
11 Docket ID: EPA-HQ-OAR-2014-0471 available at: https://www.regulations.gov/docket?D=EPA-HO-OAR-2Q 14-
0471
Page 58 of 486
-------
coordinate with the OAR and refer action regarding risk from ambient air emissions of 1-BP to the
CAA. EPA has determined that risk from emissions to the ambient air of 1 -BP could be eliminated
or reduced to a sufficient extent by actions taken under the CAA. The CAA contains a list of HAPs
and provides EPA with the authority to add to that list upon a showing by a petitioner that
"emissions, ambient concentrations, bioaccumulation, or deposition" of a substance that is an "air
pollutant" are "known to cause or may reasonably be anticipated to cause adverse effects to human
health or adverse environmental effects" as specified in the under CA A section 112(b)(3). For
stationary source categories emitting HAP, the CAA requires EPA to issue technology-based
standards that require maximum achievable control technology (MACT). Eight years after
promulgation of a standard, the CAA requires a residual risk review to ensure promulgated
standards adequately protect public health and the environment. If residual risk is identified, the
CA A directs EPA to revise standards to address the residual risk and ensure the standards
adequately protect public health and the environment. The CA A thereby provides EPA with
comprehensive authority to regulate emissions to ambient air of any hazardous air pollutant. OAR
will use the authorities in the CAA to protect against risk from emissions to the ambient air of 1 -
BP and potential impacts to the public health and the environment. As a result, EPA did not
evaluate hazards or exposures to the general population or terrestrial species from emissions to the
ambient air of 1-BP.
EPA did not include the following disposal pathways in this risk evaluation due to risks being
addressed by RCRA and SDWA:
• Releases from hazardous waste incinerators,
• On-site releases to land going to underground injection systems,
• On-site releases to RCRA Subtitle C hazardous waste landfills,
• On-site releases to land from RCRA Subtitle D municipal solid waste landfills,
• Exposures to the general population (including susceptible populations) or terrestrial
species from such releases, and
• On-site release to land from industrial non-hazardous and construction/demolition waste
landfills.
1-BP is regulated as a hazardous waste, waste code D001 (ignitable liquids, 40 CFR 261.21). The
general RCRA standard in section 3004(a) for the technical (regulatory) criteria that govern the
management (treatment, storage, and disposal) of hazardous waste {i.e., Subtitle C) are those
"necessary to protect human health and the environment," RCRA 3004(a). The regulatory criteria
for identifying "characteristic" hazardous wastes and for "listing" a waste as hazardous also relate
solely to the potential risks to human health or the environment. 40 C.F.R. §§ 261.11, 261.21-
261.24. RCRA statutory criteria for identifying hazardous wastes require EPA to "tak[e] into
account toxicity, persistence, and degradability in nature, potential for accumulation in tissue, and
other related factors such as flammability, corrosiveness, and other hazardous characteristics."
Subtitle C controls cover not only hazardous wastes that are landfilled, but also hazardous wastes
that are incinerated (subject to control under RCRA Subtitle C) or injected into UIC Class I
Page 59 of 486
-------
hazardous waste wells (subject to joint control under Subtitle C and the Safe Drinking Water Act
(SDWA)). While permitted and managed by the individual states, municipal solid waste landfills
are required by federal regulations to implement some of the same requirements as Subtitle C
landfills. Industrial non-hazardous and construction/demolition waste landfills are primarily
regulated under state regulatory programs. States must also implement limited federal regulatory
requirements for siting, groundwater monitoring, and corrective action, and a prohibition on open
dumping and disposal of bulk liquids. States may also establish additional requirement such as for
liners, post-closure and financial assurance, but are not required to do so.
1.4,3 Conceptual Models
The conceptual models for this final risk evaluation are shown in Figure 1-3, Figure 1-4, and
Figure 1-5. EPA considered the potential for hazards to human health and the environment
resulting from exposure pathways outlined in the preliminary conceptual models of the 1-BP Scope
Document (U.S. EPA. 2017d). These conceptual models indicate where potential exposures to 1-
BP may result from industrial and commercial activities, consumer activities and uses, and
environmental releases and wastes. The problem formulation documents refined the initial
conceptual models and analysis plans that were provided in the Scope Documents (U.S. EPA.
2018c).
The pathways that are included in the final risk evaluation but received no additional analysis
beyond the results of a screening level analysis or consideration of chemical-specific properties
that were presented in the Problem Formulation (U.S. EPA. 2018c) are: water (drinking water;
wastewater releases to surface water and resulting exposures to aquatic species); and exposure to
terrestrial and aquatic species via land application of biosolids to soil and through volatilization
and runoff. The analysis of these pathways is included in this final risk evaluation so that EPA can
carry the findings forward to a risk determination.
EPA did not conduct further evaluation of potential risks resulting from exposure via drinking
water pathways beyond what was presented in the Problem Formulation (U.S. EPA. 2018c). As
described in the problem formulation, there is no data of 1-BP found in U.S. drinking water. TRI
reporting from 2016 indicates zero pounds released to POTWs and five pounds released directly to
water. TRI reporting from 2017 and 2018 indicate only one pound released to water per year. In
addition, 1-BP is slightly soluble in water and volatilizes rapidly from water. As such, it is not
expected to be present in drinking water supplied from public water systems.
Releases to wastewater or surface water are included in the scope of the risk evaluation, but have
not been further analyzed since the Problem Formulation (U.S. EPA. 2018c). As discussed in the
problem formulation, 1-BP is volatile and has a relatively high Henry's law constant. 1-BP is
somewhat biodegradable and is not expected to sorb to solids in wastewater. Additionally, EPA's
STP WTP model predicts 73% removal of 1-BP by volatilization in activated sludge treatment and
1% partitioning to biosolids. 1-BP discharged in wastewater treatment plant effluent to the aquatic
environment would be subject to volatilization and biodegradation thereby reducing aquatic
exposure. Although 1-BP is not a priority pollutant, 2016 TRI reporting indicates zero pounds
released to POTWs and five pounds released directly to water, suggesting existing restrictions for
Page 60 of 486
-------
discharge to POTWs limits discharge of 1-BP to POTWs and ultimately to surface water. Based on
the characteristics of environmental fate and industrial release information, exposure to the general
population via surface water, drinking water and sediment is expected to be low. A screening-level
comparison of estimated environmental exposure concentrations with environmental hazard
thresholds was conducted in the problem formulation and indicated that risks were unlikely to
result to aquatic species (both water-column and sediment dwelling) as a result of releases to
surface water. This screening-level analysis has been carried over to the final risk evaluation from
the Problem Formulation and is presented in Section 4.1. Consistent with the analysis plan of the
Problem Formulation, no further analysis was conducted on these pathways.
Similarly, EPA included releases to terrestrial species (including soil-dwelling species) via land
application of biosolids to soils within the scope of the risk evaluation, but no further analysis was
conducted in this risk evaluation beyond what was presented in the Problem Formulation (U.S.
EPA. 2018c). As mentioned above, exposure to terrestrial species via releases to air wasre not
included in the scope of the assessment. Based on the log Koc of 1.6, 1-BP is not expected to
adsorb strongly to sediment or soil. If present in biosolids, 1-BP is expected to associate with the
aqueous component and volatilize to air as the biosolids are applied to soil and allowed to dry. The
high vapor pressure and other fate properties of 1-BP indicates soil is likely not a viable pathway
of exposure for terrestrial, sediment or ecological species as 1-BP is expected to volatilize rapidly
from soil. This is explained further in Section 3.1.3.
As explained in Section 1.4.2 of this final risk evaluation, EPA has utilized its TSCA authorities to
coordinate with the Office of Air and Radiation regarding risk from ambient air emissions of 1-BP.
EPA has determined that risk from ambient air emissions of 1-BP could be eliminated or reduced
to a sufficient extent by actions taken under the CAA. As a result, EPA did not evaluate hazards or
exposures to the general population or terrestrial species from ambient air emissions of 1-BP in this
risk evaluation.
Page 61 of 486
-------
INDUSTRIAL AND COMMERCIAL
ACTIVITIES / USES
EXPOSURE PATHWAY
EXPOSURE ROUTE
RECEPTORS0
HAZARDS
Manufacturing
Processing:
> As reactant
> Incorporated into
formulation, mixture,
or reaction product
> Incorporated into
article
• Repackaging
Recycling
Solvents for Cleaning
and Degreasing
Adhesives
and Sealants
Cleaning and Furniture
Care Products
Other Uses
Waste Handling,
Treatment and Disposal
Liquid Contact
Vapor/ Mist
Liquid Contact, Vapor
Wastewater, Liquid Wastes and Solid Wastes
(See Figure 1-5}
Occupational
Non-Users
Workers,
~( Occupational
Non-Users
Inhalation
Hazards Potentially Associated with
Acute and/or Chronic Exposures
Workers
Derma
Occupations
Non-Users
Workers,
Occupational
Non-Users
Inhalation
KEY:
GrayText: Uses or Receptors thatwere not
further analyzed
~ Pathways that were further analyzed
*" Pathways that were not further analyzed
Figure 1-3.1-BP Conceptual Model for Industrial and Commercial Activities and Uses: Potential Exposures and Hazards
The conceptual model presents the exposure pathways, exposure routes and hazards to human receptors from industrial and commercial activities and uses of 1 -BP that
EPA analyzed in this risk evaluation.
aSome products are used in both commercial and consumer applications. Additional uses of 1-BP are included in Table 1-4.
Page 62 of 486
-------
b Exposure may occur through mists that deposit in the upper respiratory tract, however based on physical-chemical properties, mists of 1 -BP will likely be rapidly
absorbed in the respiratory tract or evaporate and were considered in the inhalation exposure assessment.
°Receptors include potentially exposed or susceptible subpopulations.
dEPA also considered the effect that engineering controls and/or personal protective equipment have on occupational exposure levels.
CONSUMER ACTIVITIES/USES EXPOSURE PATHWAY EXPOSURE ROUTE RECEPTORS0 HAZARDS
Consumers
Bystanders
Dermal*3, Oralb,
Inhalation
Vapor, Liquid Contact
Wastewater, Liquid Wastes and Solid Wastes
s Figure 1-5}
Vapor/Mist
Liquid Contact
Dermal
Inhalation
Consumer Handling and
Disposal of Waste
Other Uses
e.g., insulation
Hazards Potentially Associated with
Acute Exposures
KEY:
Gray Text: Use, Route, or Receptor that were not
further analyzed
—~ Pathways that were further analyzed
~ Pathways that were not further analyzed
Other Uses
e.g., adhesive accelerant,
refrigerant flush, mold cleaning anc
release product
Cleaning and Furniture Care
Products
e.g., engine degreasing.
Spot cleaner, stain remover, liquid
cleaner, liquid spray/aerosol
cleaner
Solvents (for cleaning or
degreasing)
e.g., aerosol spray
degreaser/deaner
Figure 1-4.1-BP Conceptual Model for Consumer Activities and Uses: Potential Exposures and Hazards
Page 63 of 486
-------
The conceptual model presents the exposure pathways, exposure routes and hazards to human receptors from consumer activities and uses of 1-BP that EPA analyzed
in this risk evaluation.
aSome products are used in both commercial and consumer applications. Additional uses of 1-BP are included in Table 1-4.
b Dermal exposure may occur through skin contact with liquids; ingestion is anticipated to be low since 1-BP is expected to be absorbed in the lung quickly and not
have appreciable ability to travel up the mucosal elevator and be swallowed.
°Receptors include potentially exposed or susceptible subpopulations.
Page 64 of 486
-------
RELEASES AN D WASTES FROM
INDUSTRIAL / COMMERCIAL / CONSUMER USES
EXPOSURE PATHWAY
EXPOSURE ROUTE
RECEPTORS c
HAZARDS
industrial Pre-
Treatrnerrtor
Industrial WW I
Wastewater or
liquid Wastes3
Ir'M
discharge .
-
3 I
i;
l!
Biosollds
. jt\..
Aquatic
Species
.4;
Oral, Dermal
/ Terrestrial
Species
Low Hazard Associated with Acute and/or
Chronic Exposures
KEY:
GrayTexl: Use, Route, or Receptor thatwere not
further analyzed
— H*" Pathways that were not further analyzed
Figure 1-5.1-BP Conceptual Model for Environmental Releases and Wastes: Potential Exposures and Hazards
The conceptual model presents the exposure pathways, exposure routes and hazards to environmental receptors from environmental releases and wastes of 1-BP that
EPA analyzed in this risk evaluation.
Page 65 of 486
-------
industrial wastewater may be treated on-site and then released to surface water (direct discharge), or pre-treated and released to publicly owned treatment works
(POTW) (indirect discharge).
bPresence of mist is not expected. Dermal and oral exposures are expected to be low.
°Receptors include potentially exposed or susceptible subpopulations.
Page 66 of 486
-------
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 when making decision under
Section 6 and to 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 CFR 702.33).
To meet the TSCA science standards, EPA was guided by the systematic review process described in the
Application of Systematic Review in TSCA Risk Evaluations document (U.S. EPA. 2018a). 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 available information. EPA defines "reasonably available information" to mean
information that EPA possesses, or can reasonably obtain and synthesize for use in risk evaluations,
considering the deadlines for completing the evaluation (40 CFR 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, EPA 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 Information Collection
EPA planned and conducted a comprehensive literature search based on key words related to the
different discipline-specific evidence supporting the risk evaluation (e.g., environmental fate and
transport; environmental release and occupational exposure; exposure to general population, consumers
and environmental exposure; and environmental and human health hazard). 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 1-BP is described in the Strategy for Conducting Literature Searches for 1-Bromopropane (1-
BP): Supplemental Document to the TSCA Scope Document (U.S. EPA. 2017e). and the results of the
title and abstract screening process were published in the Strategy for Conducting Literature Searches
for 1-BP (CASRN106-94-5) Bibliography: Supplemental File for the TSCA Scope Document, EPA-HQ-
QPPT-2016-0741-0047Y
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 considered relevant to the risk evaluation.
Screening decisions were made based on eligibility criteria documented in the form of the "populations,
Page 67 of 486
-------
exposures, comparators, and outcomes (PECO) framework or a modified framework"12. Data sources
that met the criteria were carried forward to the data evaluation stage. The inclusion and exclusion
criteria for full text screening for 1-BP are available in Appendix F of the June 2018 Problem
Formulation (U.S. EPA. 2018c).
Although EPA conducted a comprehensive search and screening process as described above, EPA made
the decision to leverage the literature published in previous assessments13 when identifying relevant key
and supporting data14 and information for developing the 1-BP risk evaluation. This is discussed in the
Strategy for Conducting Literature Searches for 1-Bromopropane (1-BP): Supplemental Document to
the TSCA Scope Document (U.S. EPA. 2017e). In general, many of the key and supporting data sources
were identified in the comprehensive Strategy for Conducting Literature Searches for 1-BP (CASRN
106-94-5) Bibliography: Supplemental File for the TSCA Scope Document, EP A-HQ-QPPT-2016-0741 -
0047). However, there were instances when EPA missed relevant references 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 Evaluations
document (U.S. EPA. 2018a). Other relevant key and supporting references were identified through
targeted supplemental searches to support the analytical approaches and methods in the 1-BP risk
evaluation (e.g., to locate specific information for exposure modeling) or to identify new data and
information published after the date limits of the initial search.
EPA used previous chemical assessments to quickly identify relevant key and supporting information as
a pragmatic approach to expedite the quality evaluation of the data sources, but many of those data
sources were already captured in the comprehensive literature as explained above. EPA also considered
newer information not taken into account by previous chemical assessments as described in the Strategy
for Conducting Literature Searches for 1-Bromopropane (1-BP): Supplemental Document to the TSCA
Scope Document (U.S. EPA. 2017e). EPA then evaluated the confidence of the key and supporting data
sources as well as newer information instead of evaluating the confidence of all the underlying evidence
ever published on 1-BP fate and transport, environmental releases, environmental and human exposure
and hazard potential. Such a comprehensive evaluation of all of the data and information published for
1-BP would be extremely labor intensive and could not be achieved under the TSCA statutory deadlines
for most chemical substances especially those that have a data rich database. EPA also considered how
12 A PESO statement was used during the Ml 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.
13 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-BP: Supplemental File for the TSCA Scope Document
(U.S. EPA. 2017e)
14 Key and supporting data and information are those that support key analyses, arguments, and/or conclusions in the risk
evaluation.
Page 68 of 486
-------
this evaluation of the key and supporting data and newer information would change the previous
conclusions presented in the previous assessments.
Using this pragmatic approach, EPA evaluated the confidence of the key and supporting data sources as
well as newer information instead of evaluating the confidence of all the underlying evidence published
on 1-BP's fate and transport, environmental releases, environmental and human exposure and hazards.
This allowed EPA to maximize the scientific and analytical efforts of other regulatory and non-
regulatory agencies by accepting for the most part the relevant scientific knowledge gathered and
analyzed by others except for influential information sources that may have an impact on the weight of
the scientific evidence and ultimately the risk findings. The influential information (i.e., key/supporting)
came from a smaller pool of sources subject to the rigor of the TSCA systematic review process to
ensure that the risk evaluation uses the best available science and the weight of the scientific evidence.
Figure 1-6 to Figure 1-9 depict the literature flow diagrams illustrating the results of this process for
each scientific discipline-specific evidence supporting the risk evaluation. Each diagram provides the
total number of references at the start of each systematic review stage (i.e., data search, data screening,
data evaluation, data extraction/data integration) and those excluded based on criteria guiding the
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
risk evaluation as described above. These data sources are depicted as "key/supporting data sources" in
the literature flow diagrams. 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 stages
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
(Figure 1-7).
Key/Supporting
Data Sources (n=0)
Excluded References
(n=l,265)
Data Extraction/Data Integration
(n=6)
Data Search Results (n=l,283)
Data Screening (1,283)
Data Evaluation (n=18)
Excluded:
References that are
unacceptable based
on the evaluation
criteria (n=12)
Figure 1-6. Literature Flow Diagram for Environmental Fate and Transport Data Sources
Page 69 of 486
-------
Note: Literature search results for the environmental fate and transport of 1-BP yielded 1,283 studies. Only the environmental
fate and transport pathway for air was identified in the conceptual model. Other fate studies moving forward were used to
inform general discussion of the enviromnental fate of 1-BP but were not used directly in the risk evaluation. 1,265 studies
were determined to be off topic. The remaining 18 studies entered full text screening for the determination of relevance to the
risk evaluation. All remaining studies were determined to be relevant and entered data evaluation. Twelve studies were
deemed unacceptable based on the evaluation criteria for fate and transport studies and the remaining six studies were carried
forward to data extraction.
* These are key and supporting studies from existing assessments (e.g., EPA IRIS assessments, ATSDR assessments, ECHA
dossiers) that were considered highly relevant for the TSCA risk evaluation. These studies bypassed the data screening step
and moved directly to the data evaluation step.
n= 45
Key/supporting
data sources
(n= 52)
Excluded References (n= 1,249)
Data Sources that were not
integrated (n=37)
Data Search Results (n= 1,294)
Data Integration (n= 60)
Data Extraction/Data Evaluation (n= 97)
Data Screening (n= 1,294)
Figure 1-7. Literature Flow Diagram for Environmental Release and Occupational Exposure Data
Sources
Note: Literature search results for enviromnental release and occupational exposure yielded 1,294 data sources. Of these data
sources, 45 were determined to be relevant for the risk evaluation through the data screening process. In addition, EPA
identified several data gaps and performed a supplemental, targeted search to fill these gaps (e.g., to locate information
needed for exposure modeling). The supplemental search yielded 52 relevant data sources that bypassed the data screening
step and were evaluated and extracted.
*The quality of data in these sources (n=37) were acceptable for risk assessment purposes, but they were ultimately excluded
from further consideration based on EPA's integration approach for enviromnental release and occupational exposure
data/information. EPA's approach uses a hierarchy of preferences that guide decisions about what types of data/information
are included for further analysis, synthesis and integration into the enviromnental release and occupational exposure
assessments. EPA prefers using data with the highest rated quality among those in the higher level of the hierarchy of
preferences (i.e., data > modeling > occupational exposure limits or release limits). If warranted, EPA may use
data/information of lower rated quality as supportive evidence in the enviromnental release and occupational exposure
assessments. Sources that contain only enviromnental release data for the air pathway were evaluated but not integrated,
because this pathway was determined to be out of scope during development of the risk evaluation. The data integration
strategy for environmental release and occupational exposure data is discussed in Appendix K of the document titled "Final
Risk Evaluation for 1-BP, Supplemental File: Information on Occupational Exposure Assessment (EPA. 2019f)."
Page 70 of 486
-------
Excluded References (n = 91)
Data Evaluation (n = 21)
Data Extraction/Data Integration (n = 11)
Data Screening (n = 112)
Data Search Results (n = 112)
"Excluded: References that are unacceptable
based on data evaluation criteria, not primary
sources, or not extractable (n = 10)
Figure 1-8. Literature Flow Diagram for Consumer and Environmental Exposure Data Sources
EPA conducted a literature search to determine relevant data sources for assessing exposures for 1 -BP within the scope of the
risk evaluation. This search identified 112 data sources. Of these, 91 were excluded during the screening of the title, abstract,
and/or full text and 21 data sources were recommended for data evaluation. Following the evaluation process, 11 references
were forwarded for further extraction and data integration.
Page 71 of 486
-------
Excluded References due to
ECOTOX Criteria
(r = 30)
Data Extraction I Data Integration
-------
Key/supporting data
sources (n = 14)
Excluded References (n = 784)
Excluded: Refs that are
unacceptable based on
evaluation criteria (n = 5)
Data Search Results (n = 813)
Data Screening (n = 799)
Data Extraction/Data Integration (n = 24)
Data Evaluation(n = 29)
Figure 1-10. Literature Flow Diagram for Human Health Hazard Data Sources
Note: The literature search results for human health hazard of 1-BP yielded 813 studies. This included 14 key and supporting
studies identified from previous EPA assessments. Of the 799 new studies screened for relevance, 784 were excluded as off
topic. The remaining 15 new studies together with the 14 key and supporting studies entered data evaluation. Five studies
were deemed unacceptable based on the evaluation criteria for human health hazard data sources and the remaining 24
studies were carried forward to data extraction/data integration. Additional details can be found in the Strategy for
Conducting Literature Searches for 1 -Bromopropane (1-BP): Supplemental Document to the TSCA Scope Document (U.S.
EPA 2017e).
1.5.2 Data Evaluation
During the data evaluation stage, EPA assesses the quality of the data sources using the evaluation
strategies and criteria described in Application of Systematic Review in TSCA Risk Evaluations (U.S.
EPA. 2018a). For the data sources that passed full-text screening, EPA evaluated their quality and each
data source received an overall confidence of high, medium, low or unacceptable.
The results of these data quality evaluations are provided in Sections 2.1 (Fate and Transport), 2.2
(Environmental Exposures), 2.3 (Human Exposures), 3.1 (Environmental Hazards) and 3.2 (Human
Health Hazards). Additional information is provided in the appendices of the main document.
Page 73 of 486
-------
Supplemental files15 also provide details of the data evaluations including individual metric scores and
the overall study score for 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, relevancy, coherence and biological
plausibility to make final conclusions regarding the weight of the scientific evidence. As stated in
Application of Systematic Review in TSCA Risk Evaluations (U.S. EPA. 2018a). data integration
involves transparently discussing the significant issues, strengths, and limitations as well as the
uncertainties of the reasonably available information and the major points of interpretation (U.S. EPA.
2018d).
EPA used previous assessments to identify key and supporting information and then analyzed and
synthesized available lines of evidence regarding 1-BP's chemical properties, environmental fate and
transport properties, 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
available information on potentially exposed or susceptible subpopulations.
The exposures and hazards sections describe EPA's analysis of the influential information {i.e., key and
supporting data) that were found acceptable based on the data quality reviews as well as discussion of
other scientific knowledge using the approach described in Section 1.5.1. The exposure section also
describes whether aggregate or sentinel exposures to a chemical substance were considered under the
conditions of use within the scope of the risk evaluation, and the basis for that consideration.
15 The supplemental files accompanying the risk evaluation are listed in Appendix B.
• Final Risk Evaluation for 1-Bromopropane (1-BP), Systematic Review Supplemental File: Updates to the Data Quality Criteria
for Epidemiological Studies. (EPA. 201901
• Final Risk Evaluation for 1-Bromopropane (1-BP), Systematic Review Supplemental File: Data Quality Evaluation of
Environmental Fate and Transport Studies. fEPA. 201911
• Final Risk Evaluation for 1-Bromopropane (1-BP), Systematic Review Supplemental File: Data Quality Evaluation for Consumer
Exposure fEPA. 2019il
• Final Risk Evaluation for 1-Bromopropane (1-BP), Systematic Review Supplemental File: Data Quality Evaluation of
Environmental Release and Occupational Exposure Data. fEPA. 2019ml
• Final Risk Evaluation for 1-Bromopropane (1-BP), Systematic Review Supplemental File: Data Quality Evaluation of
Environmental Release and Occupational Exposure Data for Common Sources. fEPA. 2019nl
• Final Risk Evaluation for 1-Bromopropane (1-BP), Systematic Review Supplemental File: Data Quality Evaluation of Ecological
Hazard Studies. CEPA. 2019k).
• Final Risk Evaluation for 1-Bromopropane (1-BP), Systematic Review Supplemental File: Data Quality Evaluation of Fluman
Flealth Flazard Studies - Epidemiologic Studies. fEPA. 201901
• Final Risk Evaluation for 1-Bromopropane (1-BP), Systematic Review Supplemental File: Data Quality Evaluation of Fluman
Health Hazard Studies. EPA-HQ-OPPT-2019-0235 fEPA. 2019ol
• Final Risk Evaluation for 1-Bromopropane (1-BP), Systematic Review Supplemental File: Data Extraction Tables for
Environmental Fate and Transport Studies. fEPA. 2019il
• Final Risk Evaluation for 1-Bromopropane (1-BP), Systematic Review Supplemental File: Data Extraction for Consumer
Exposure fEPA. 2019hl
Page 74 of 486
-------
2 EXPOSURES
This section describes EPA's approach to assessing environmental and human exposures. First, the fate,
transport, and releases of 1-BP into the environment are assessed; this information is integrated into an
assessment of occupational, consumer, and environmental exposures for 1-BP. 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.
Exposure equations and selected values used in the exposure assessment are presented in the following
sections. More specific information is provided in Supplementary Files (see Appendix B).
Following the inclusion of 1-BP on EPA's workplan list in 2012, EPA published a 2016 Draft Risk
Assessment (U.S. EPA. 2016c) prior to passage of the Lautenberg Act amendments to TSCA. Since that
time, EPA has published a Scope of the Risk Evaluation for 1-BP in 2017 (Scope Document; EPA-HQ-
OPPT-2016-0741 -0049). and Problem Formulation in 2018 (U.S. EPA. 2018c). EPA has incorporated
the following refinements based on public comments and review of data since work began on 1-BP:
• Refined parameters for occupational exposure models;
• Expanded consumer uses evaluated for inhalation exposure; and
• Included evaluation for dermal exposure from industrial, commercial, and consumer use
scenarios.
2.1 Fate and Transport
The environmental fate studies considered for this assessment are summarized in Table 2-1 and were
supplemented by an updated literature search following Problem Formulation (U.S. EPA. 2018c).
2,1,1 Fate and Transport Approach and Methodology
EPA identified fate data for 1-BP through an extensive literature search, as described in EPA's Strategy
for Conducting Literature Searches for 1-Bromopropane (1-BP): Supplemental Document to the TSCA
Scope Document (U.S. EPA. 2017e). Published and non-published data sources, including key and
supporting studies identified in previous assessments, were evaluated during this process. EPA also
relied heavily on the 2016 Draft Risk Assessment (U.S. EPA. 2016c) to inform the fate assessment for
the final risk evaluation. EPA assessed the quality of a study based on the data quality criteria described
in the Application of Systematic Review in TSCA Risk Evaluations (U.S. EPA. 2018a). Other fate
estimates were based on modeling results from EPI Suite™ (U.S. EPA. 2012b). a predictive tool for
physical-chemical and environmental fate properties. The data evaluation tables describing their review
can be found in the supplemental document, Systematic Review Supplemental File: Data Quality
Evaluation of Environmental Fate and Transport Studies (EPA. 20191).
The 1-BP environmental fate characteristics and physical-chemical properties used in fate assessment
are presented in Table 2-1 and Table 1-1, respectively. EPA used EPI Suite™ estimations and
reasonably available fate data to characterize the environmental fate and transport of 1-BP. As part of
Problem Formulation (U.S. EPA. 2018c). EPA also analyzed the air, water, sediment, land application
and biosolids pathways and determined no further analysis would be conducted on these pathways. The
Page 75 of 486
-------
results of the analyses are described in the Problem Formulation in June 2018 (U.S. EPA. 2018c) and
presented again in Appendix C. Both this section and Appendix C may also cite other data sources as
part of the reasonably available evidence on the fate and transport properties of 1- BP. EPA subjected
these other data sources to the later phases of the systematic review process (i.e., data evaluation and
integration).
2.1.2 Summary of Fate and Transport
1-BP is a volatile liquid with high vapor pressure, high water solubility, and high mobility in soil. It is
expected to exhibit low adsorption to soils and thus can migrate rapidly through soil to groundwater. 1-
BP is slowly degraded by hydroxy radical oxidation when released to the atmosphere (half-life 9-12
days). Based on this estimated half-life in air, long range transport via the atmosphere is possible (see
Appendix C). Volatilization and microbial degradation influence the fate of 1-BP when released to
water, sediment, or soil. The vapor pressure of 1-BP is 110 mm Hg at 20°C, its water solubility is 2.45
g/L and its Henry's law constant is calculated as 7.3 X 10 "3 atm-m3/mol. These physical-chemical
properties input to the Volatilization from Water (WVol) model in EPISuite™ indicate that 1-BP will
volatilize from a model river with a half-life on the order of an hour and from a model lake on the order
four days. The Level III Fugacity model in EPA's EPISuite ™ was used to estimate the steady state
partitioning of 1-BP between air, water, soil and sediment. The model estimated that when 1-BP is
continuously released to water, 80% of the mass would remain in water and 19% in air due in part to its
water solubility. Biotic and abiotic degradation rates ranging from days to months have been reported
(U.S. EPA. 2012c; Sakuratani et al.. 2005; Mabev and Mill. 1978). Intermittent releases of 1-BP are not
expected to result in long-term presence in the aquatic compartment due to volatilization and
biodegradation.
1-BP does not meet criteria to be classified as persistent or bioaccumulative (Federal Register. 1999).
Biotic and abiotic degradation studies have not shown this substance to be persistent (overall
environmental half-life of less than two months). No measured bioconcentration studies for 1-BP are
available. An estimated bioaccumulation factor of 12 (U.S. EPA. 2012b) suggests that bioconcentration
and bioaccumulation in aquatic organisms are low (i.e., bioconcentration/bioaccumulation factors of less
than 1000).
Table 2-1. Summary of Environmental Fate and Transport Properties
Property or Endpoint
Valuea
References
Study Quality
Direct photodegradation
Not expected to undergo direct
photolysis
HSDB (2017)
High
Indirect photodegradation
9-12 days (estimated for
atmospheric degradation)
EPI Suite Version 4.10
(U.S. EPA. 2012b)
High
Hydrolysis half-life
26 days
U.S. EPA (2016c)
(Mabev and Mill. 1978)
Low
Biodegradation
70% in 28 days (OECD 301C)
(Sakuratani et al.. 2005)
Medium
Bioconcentration factor (BCF)
11 (estimated)
EPISuite Version 4.10
(U.S. EPA. 2012b)
High
Page 76 of 486
-------
Property or Endpoint
Valuea
References
Study Quality
Bioaccumulation factor (B AF)
12 (estimated)
EPISuite Version 4.10
(U.S. EPA. 2012b)
High
Organic carbon:water partition
coefficient (Log Koc)
1.6 (estimated)
EPISuite Version 4.10
(U.S. EPA. 2012b)
High
a Measured unless otherwise noted
2.1.3 Assumptions and Key Sources of Uncertainty for Fate and Transport
The EPI Suite™ model (Version 4.1) (U.S. EPA. 2012b) was used to estimate several environmental
fate properties for 1-BP in the absence of data (see Table 2-1). A full discussion of the performance of
the individual property estimation methods used in EPISuite is available in the EPI Suite™ help files.
No data on the bioconcentration or bioaccumulation potential of 1-BP was found and in the absence of
measured values, bioconcentration and bioaccumulation factors were estimated. These properties were
used to inform decisions on whether 1-BP has the potential to build up in aquatic and terrestrial species
via exposure to water and diet and whether fish ingestion pathways of exposure should be included in
the final risk evaluation. EPA compared measured BCF values for a series of halogenated ethanes and
propanes and EPI Suite™ estimated BCF values. The largest observed error for BCF estimation was
0.56 log units and none of the chemicals had measured Log BCF values greater than 1.6. Thus, even if
the estimate for 1-BP was subject to the maximum observed error, its log BCF would be expected to fall
in the range of 0.5 to 1.5, indicating low bioconcentration potential (BCF <1000).
2.2 Environmental Exposures
2.2.1 Environmental Exposures Approach and Methodology
The manufacturing, processing, use and disposal of 1-BP can result in releases to the environment.
Environmental exposures via air, water, sediment, biosolids and soil are all discussed in the
environmental risk characterization section (Section 4.1). The predominance of these exposures is via
the air pathway as reported releases to water was limited to 5 pounds in 2016 (See Appendix H). EPA
did not conduct additional analysis of exposures to aquatic or terrestrial exposures beyond what was
presented in the 2018 Problem Formulation (U.S. EPA. 2018c).
As described in the Problem Formulation (U.S. EPA. 2018c). an aquatic exposure assessment was
conducted using 2016 TRI release information (U.S. EPA. 2017f) to model predicted surface water
concentrations near discharging facilities. To examine whether near-facility surface water concentrations
could approach aquatic concentrations of concern (COC) for 1-BP, EPA employed a conservative
approach, using available modeling tools and data to estimate near-facility surface water concentrations
resulting from reported releases of 1-BP to surface water. High-end surface water concentrations (i.e.,
those obtained assuming low receiving water body stream flows) from all E-FAST 2014 runs ranged
from 0.19 |ig/L to 77.9 |ig/L. The E-FAST results were compared to the acute concentrations of concern
of 13,460 |ig/L (96-hour fish LCso (Geiger et al.. 1988)) and 3,640 |ig/L (algae EC50 based on
ECOSAR modeling) and the chronic concentrations of concern of 673 |ig/L (fish chronic value
Page 77 of 486
-------
estimated from Geiger (1988)) and 470 |ig/L (daphnia ChV based on ECOSAR modeling) (see Table
4-1). This aquatic exposure analysis and additional details about the approach and results are presented
in Appendix H. The analysis and determination of risk are presented in the risk characterization and risk
determination sections, respectively.
2.3 Human Exposure Assessment
2.3.1 Occupational Exposures
EPA assessed occupational exposures following the analysis plan published in the June 2018 Problem
Formulation (U.S. EPA. 2018c). Specific assessment methodology is described in further detail below
for each type of assessment. Additional details of EPA's occupational exposure assessment can be found
in the 1-BP Supplemental File: Supplemental Information on Occupational Exposure Assessment (EPA.
2019f). Table 2-2 presents a crosswalk of the industrial and commercial conditions of use (see Table
1-4) and the section of the risk evaluation in which occupational exposure for that use is assessed.
For the purpose of this assessment, EPA assumes workers and occupational non-users (ONU) are men
and women of reproductive age (16 or older), including adolescents (16 to <21 years old). EPA
guidance16 defines children as 0 to <21 years old and workers can be as young as 16 years old.
Therefore, EPA defines adolescent workers as 16 to <21 years old. EPA also considers exposure to
children who may be present at the workplace, such as small family-owned dry cleaners, an
occupational exposure scenario recommended for assessment from the peer review of the 2016 Draft
Risk Assessment of 1-BP (U.S. EPA. 2016c).
Table 2-2. Crosswalk of Subcategories of Use Listed in the Problem Formulation Document to
Occupational Conditions of Use Assessed in the Final Risk Evaluation
Life Cycle Stage
Category a
Subcategory b
Assessed Condition of Use
Manufacture
Domestic manufacture
Domestic manufacture
Section 2.3.1.5 -
Manufacture
Import
Import
Section 2.3.1.6 - Import
Processing
Processing as a reactant
Intermediate in all other basic
inorganic chemical manufacturing,
all other basic organic chemical
manufacturing, and pesticide,
fertilizer and other agricultural
chemical manufacturing
Section 2.3.1.7 - Processing
as a Reactant
16 U.S. EPA. Guidance on Selecting Age Groups for Monitoring and Assessing Childhood Exposures to Environmental
Contaminants (Final). EPA/630/P-03/003F. Available online at:
https://www.epa.gov/risk/guidance-selecting-age-groups-monitoring-and-assessing-childhood-exposures-environmental
Page 78 of 486
-------
Life Cycle Stage
Category a
Subcategory b
Assessed Condition of Use
Processing
Processing - incorporating
into formulation, mixture or
reaction product
Solvents for cleaning or degreasing
in manufacturing of:
- all other chemical product and
preparation
- computer and electronic product
- electrical equipment, appliance
and component
- soap, cleaning compound and
toilet preparation
- services
Section 2.3.1.8 - Processing
- Incorporation into
Formulation, Mixture, or
Reaction Product
Processing - incorporating
into articles
Solvents (which become part of
product formulation or mixture) in
construction
Section 2.3.1.9 - Processing
- Incorporation into Articles
Repackaging
Solvent for cleaning or degreasing in
all other basic organic chemical
manufacturing
Section 2.3.1.10 -
Repackaging
Recycling
Recycling
Section 2.3.1.21 - Disposal,
Recycling
Distribution in
commerce
Distribution
Distribution
Not assessed as a separate
operation; exposures/releases
from distribution are
considered within each
condition of use.
Batch vapor degreaser (e.g., open-
top, closed-loop)
Section 2.3.1.11 - Batch
Vapor Degreaser (Open-Top)
Section 2.3.1.12- Batch
Vapor Degreaser (Closed-
Loop)
Solvent (for cleaning or
degreasing)
In-line vapor degreaser (e.g.,
conveyorized, web cleaner)
Section 2.3.1.13- In-line
Vapor Degreaser
Industrial/ commercial
use
Cold cleaner
Section 2.4.1.13 - Cold
Cleaner
Aerosol spray degreaser/cleaner
Section 2.3.1.15 - Aerosol
Spray Degreaser/Cleaner
Adhesives and sealants
Adhesive chemicals - spray adhesive
for foam cushion manufacturing and
other uses
Section 2.3.1.18 - Adhesive
Chemicals (Spray Adhesives)
Cleaning and furniture care
products
Dry cleaning solvent
Section 2.3.1.16-Dry
Cleaning
Page 79 of 486
-------
Life Cycle Stage
Category a
Subcategory b
Assessed Condition of Use
Spot cleaner, stain remover
Section 2.3.1.17 - Spot
Cleaner, Stain Remover
Liquid cleaner (e.g., coin and scissor
cleaner)
Section 2.3.1.20 - Other Uses
Liquid spray/aerosol cleaner
Section 2.3.1.20 - Other Uses
Arts, crafts and hobby materials -
adhesive accelerant
Section 2.3.1.20 - Other Uses
Automotive care products - engine
degreaser, brake cleaner
Section 2.3.1.15 - Aerosol
Spray Degreaser/Cleaner
Anti-adhesive agents - mold cleaning
and release product
Section 2.3.1.20 - Other Uses
Building/construction materials not
covered elsewhere - insulation
Section 2.3.1.19 -
THERMAX™ Installation
Industrial/ commercial
use
Other uses
Electronic and electronic products
and metal products
Functional fluids (closed systems) -
refrigerant
Functional fluids (open system) -
cutting oils
Section 2.3.1.20 - Other Uses
Other - asphalt extraction
Other - laboratory chemicals
Temperature indicator-
coatings
Disposal
(Manufacturing,
Processing, Use)
Disposal
Municipal waste incinerator
Off-site transfer
Section 2.3.1.21 - Disposal,
Municipal waste incinerator
Recycling
Off-site waste transfer
a These categories of conditions of use appear in the Life Cycle Diagram, reflect CDR codes, and broadly represent
conditions of use of 1-BP in industrial and/or commercial settings.
b These subcategories reflect more specific uses of 1-BP.
2.3.1.1 Number of Sites and Workers Approach and Methodology
Where available, EPA determined the number of sites and workers using data reported under the
Chemical Data Reporting (CDR) Rule. The CDR Rule, issued under the TSCA, requires manufacturers
and importers to report certain information on the chemicals they produce domestically or import into
the United States. For the 2016 CDR cycle, manufacturers and importers of chemicals listed on the
TSCA inventory were required to report if their production volume exceeded 25,000 pounds at a single
site during any of the calendar years 2012, 2013, 2014 or 2015.
Page 80 of 486
-------
For conditions of use where CDR data are insufficient, EPA determined the number of sites that
manufacture, process, and use 1-BP using reasonably available market data and data from Section 3 of
the Toxics Release Inventory (TRI), "Activities and Uses of the Toxic Chemical at the Facility." In
addition, EPA determined the number of workers by analyzing Bureau of Labor Statistics (BLS) and
U.S. Census data using the methodology described in the Supplemental Information on Occupational
Exposure Assessment (EPA. 2019f).
Table 2-3 presents the confidence rating of data that EPA used to estimate number of sites and workers.
Table 2-4 presents the estimated number of sites and workers in the occupational exposure scenarios
assessed for 1-BP. Details of the estimates are available in the Supplemental Information on
Occupational Exposure Assessment (EPA. 2019f).
Table 2-3. Data Evaluation of Sources Containing General Facility Estimates
Source Reference
Data Type
Confidence Rating
Condition of Use
(U.S. EPA. 2017a)
Number of Sites and
Workers
High
Manufacture, Import, Processing as a Reactant,
Processing - Incorporation into Formulation
(U.S. BLS. 2016)
Number of Workers
High
Processing - Incorporation into Articles, all
conditions of use involving industrial and
commercial uses of 1-BP, Disposal
(Bureau. 2015)
Number of Workers
High
(IRTA. 2016)
Number of Sites
Medium
Batch Vapor Degreaser (Closed-Loop), In-line
Vapor Degreaser
(U.S. EPA. 2013c)
Number of Sites
Medium
Aerosol Spray Degreaser/Cleaner
(Enviro Tech
International. 2017)
Number of Sites
High
Dry Cleaning
(CDC. 2016)
Number of Sites
Medium
Batch Vapor Degreaser (Open-Top), Adhesive
Chemicals (Spray Adhesive)
(U.S. EPA. 2017b.
2016b)
Number of Sites
Medium
Disposal
Table 2-4. Estimated Number of Sites and Workers in the Assessed Occupational Exposure
Scenarios for 1-BP
Occupational Exposure Scenario
Number of Sites
Number of Workers
Number of ONUs
Manufacture
2
35-73
*
Import
8
31 - 103
*
Processing as a Reactant
3-27
30-72
*
Processing - Incorporation into Formulation,
Mixture, or Reaction Product
33 -99
220 - 1,046
*
Processing - Incorporation into Articles
1
15
4
Repackaging
<10
10 - <25
*
Page 81 of 486
-------
Batch Vapor Degreaser (Open-Top)
500 - 2,500
3,200 - 16,000 A
1,500 - 7,300 A
Batch Vapor Degreaser (Closed-Loop)
100
650 A
290 A
In-line Vapor Degreaser (Conveyorized)
800
5,200 A
2,300 A
Cold Cleaner
Not available +
Aerosol Spray Degreaser / Cleaner
1,000 - 5,000
2,200- 11,000 A
240 - 1,200 A
Dry Cleaning;
Spot Cleaner, Stain Remover
8
24
8
Adhesive Chemicals (Spray Adhesives)
100-280
550- 1,500 A
950 - 2,700 A
THERMAX™ Installation
Not available +
Other Uses
Not available +
Disposal, Recycling
>4
>49
>18
* - Data did not distinguish ONUs from workers.
A - Values rounded to 2 significant digits.
+ - EPA does not have reasonably information to determine the number of sites, workers, and ONUs for this scenario.
2.3.1.2 Inhalation Exposures Approach and Methodology
To assess inhalation exposure, EPA reviewed reasonably available exposure monitoring data and
mapped them to specific conditions of use. Monitoring data used in the occupational exposure
assessment include data collected by government agencies such as OSHA and NIOSH, and data found in
published literature. For each exposure scenario and worker job category ("worker" or "occupational
non-user"), where available, EPA provided results representative of central tendency and high-end
exposure levels. For datasets with six or more data points, central tendency and high-end exposures were
estimated using the 50th and 95th percentile value from the observed dataset, respectively. For datasets
with three to five data points, the central tendency and high-end exposures were estimated using the
median and maximum values.17 For datasets with two data points, the midpoint and the maximum value
were presented. Finally, datasets with only one data point were presented as-is. A dataset comprises the
combined exposure monitoring data from all studies applicable to that condition of use.
EPA assumes workers are those who directly handle 1-BP at the facility. Occupational non-users are
those who do not directly handle 1-BP but perform work in an area where the chemical is present.
For exposure assessment, where reasonably available, personal breathing zone (PBZ) monitoring data
were used to determine the time-weighted average (TWA) exposure concentration. EPA evaluated
monitoring data using the evaluation strategies laid out in the Application of Systematic Review in TSCA
Risk Evaluations (U.S. EPA. 2018a). The data are then integrated based upon the strength of the
evidence in accordance with the Data Integration Strategy for occupational exposure assessment
described in Appendix K of the Supplemental Information on Occupational Exposure Assessment (EPA.
17 If the median value is not available, EPA may use the mean (arithmetic or geometric), mode, or midpoint values of a
distribution to represent the central tendency scenario.
Page 82 of 486
-------
2019f). All occupational inhalation exposure monitoring data integrated into this risk evaluation have
either a "high" or "medium" confidence rating, as shown in Table 2-5.
For several conditions of use, EPA modeled exposure in occupational settings. The models were used to
either supplement existing exposure monitoring data or to provide exposure estimates where measured
data are unavailable. The inhalation exposure models used to assess vapor degreasing, cold cleaning,
aerosol degreasing, dry cleaning, and spot cleaning conditions of use were previously developed for, and
peer reviewed as part of the 2016 Draft Risk Assessment (U.S. EPA 2016c). and have been
subsequently refined to address peer review comments.
Measured or modeled TWA exposure concentrations are then used to calculate the Acute Concentration
(AC), Average Daily Concentrations (ADC) and Lifetime Average Daily Concentration (LADC) using
the approach and equations described in the Supplemental Information on Occupational Exposure
Assessment (EPA 2019f). In general, AC and ADC were based on a full work-week basis, 8 hr/day and
260 days/year. Therefore, for most OES they are identical. For risk estimation of developmental toxicity
endpoints however, Points of Departure (PODs) are identical for acute and chronic exposure scenarios
(Section 3.2.8) based on a single workday basis (8hr/day) and ADC is adjusted to account for the
number of working days per year out of 365.
Table 2-5. Data Evaluation of Sources Containing Occupational Exposure Data
Source Reference
Data Type
Confidence Rating
Condition of Use
(OSHA. 2013a)
PBZ Monitoring
High
Manufacture
(Enviro Tech
International. 2020)
PBZ Monitoring
High
Processing ~ Incorporation into Formulation
(Reh and Nemhauser.
2001)
PBZ Monitoring
High
Batch Vapor Degreaser
(Miller. 2019)
PBZ Monitoring
High
Batch Vapor Degreaser
(OSHA. 2013b)
PBZ Monitoring
High
Batch Vapor Degreaser, Spot Cleaner,
Adhesive Chemicals (Spray Adhesive), Cold
Cleaner
(OSHA. 2019)
PBZ Monitoring
High
Batch Vapor Degreaser, Spot Cleaner
(U.S. EPA. 2006b)
PBZ Monitoring
Medium
Batch Vapor Degreaser, Aerosol Spray
Degreaser/Cleaner
(Eisenbere and Ramsev.
2010)
PBZ Monitoring
High
Dry Cleaning
(Blando et al.. 2010)
PBZ Monitoring
High
Dry Cleaning
(NIOSH. 2002b)
PBZ Monitoring
High
Adhesive Chemicals (Spray Adhesive)
(Reh et al.. 2002)
PBZ Monitoring
High
Adhesive Chemicals (Spray Adhesive)
(NIOSH. 2003b)
PBZ Monitoring
High
Adhesive Chemicals (Spray Adhesive)
Page 83 of 486
-------
2.3.1.3 Consideration of Engineering Control and Personal Protective Equipment
OSHA requires and NIOSH recommends that employers utilize the hierarchy of controls to address
hazardous exposures in the workplace. The hierarchy of controls strategy outlines, in descending order
of priority, the use of elimination, substitution, engineering controls, administrative controls, and lastly
personal protective equipment (PPE). The hierarchy of controls prioritizes the most effective measures
first which is to eliminate or substitute the harmful chemical (e.g., use a different process, substitute with
a less hazardous material), thereby preventing or reducing exposure potential. Following elimination and
substitution, the hierarchy recommends engineering controls to isolate employees from the hazard,
followed by administrative controls, or changes in work practices to reduce exposure potential (e.g.,
source enclosure, local exhaust ventilation (LEV) systems). Administrative controls are policies and
procedures instituted and overseen by the employer to protect worker exposures. As the last means of
control, the use of PPE (e.g., respirators, gloves) is recommended, when the other control measures
cannot reduce workplace exposure to an acceptable level. The impact of respirator use on worker
exposure is addressed in Section 4.2, Human Health Risk.
OSHA's Respiratory Protection Standard (29 CFR 1910.134) provides a summary of respirator types by
their assigned protection factor (APF). OSHA defines APF to mean: the workplace level of respiratory
protection that a respirator or class of respirators is expected to provide to employees when the employer
implements a continuing, effective respiratory protection program according to the requirements of
OSHA's Respiratory Protection Standard. If respirators are necessary in atmospheres that are not
immediately dangerous to life or health, workers must use NIOSH-certified air-purifying respirators or
NIOSH-approved supplied-air respirators with the appropriate APF. Respirators that meet these criteria
include air-purifying respirators with organic vapor cartridges. Respirators must meet or exceed the
required level of protection listed in Table 2-6. Based on the APF, inhalation exposures may be reduced
by a factor of 5 to 10,000 if respirators are properly worn and fitted.
Table 2-6. Assigned Protection Factors for Respirators in OSHA Standard 29 CFR 1910.134
Type of Respirator
Quarter
Mask
Half
Mask
Full
Facepiece
Helmet/
Hood
Loose-
fitting
Facepiece
1. Air-Purifying Respirator
5
10
50
-
-
2. Power Air-Purifying Respirator
(PAPR)
-
50
1,000
25/1,000
25
3. Supplied-Air Respirator (SAR) or
Airline Respirator
-
-
-
-
-
• Demand mode
-
10
50
-
-
• Continuous flow mode
-
50
1,000
25/1,000
25
• Pressure-demand or other
positive-pressure mode
-
50
1,000
-
-
Page 84 of 486
-------
Type of Respirator
Quarter
Mask
Half
Mask
Full
Facepiece
Helmet/
Hood
Loose-
fitting
Facepiece
4. Self-Contained Breathing
Apparatus (SCBA)
-
-
-
-
-
• Demand mode
-
10
50
50
-
• Pressure-demand or other
positive-pressure mode (e.g.,
open/closed circuit)
-
-
10,000
10,000
-
Source: 29 CFR 1910.134(d)(3)(i)(A)
NIOSH and the U.S. Department of Labor's Bureau of Labor Statistics (BLS) conducted a voluntary
survey of U.S. employers regarding the use of respiratory protective devices between August 2001 and
January 2002 (NIOSH. 2001). For additional information, please refer to [Memorandum NIOSH BLS
Respirator Usage in Private Sector Firms. Docket: EPA-HQ-OPPT-2019-0500],
2.3.1.4 Dermal Exposures Approach and Methodology
Although the inhalation pathway is expected to be the primary exposure for 1-BP, dermal exposure may
be important in contributing to the overall exposure. EPA assessed dermal exposure to workers using the
Dermal Exposure to Volatile Liquids Model (modified version of the peer reviewed EPA OPPT 2-Hand
Dermal Exposure to Liquids Model) (U.S. EPA. 2013a). The model estimates 0.29 percent dermal
absorption for non-occluded exposures based on measurements from a 2011 in vitro dermal penetration
study of 1-BP conducted by Frasch et al. (2011). The report presents several occupational dermal
exposure scenarios, accounting for the potential for evaporation and glove use. The dermal exposure
assessment is described in more detail in Section 2.3.1.23.
The occupational dermal exposure model shares a common underlying methodology as the consumer
dermal exposure model in Section 2.3.2 but uses different parametric approaches due to different data
availability and assessment needs. For example, the occupational approach accounts for glove use using
protection factors, while the consumer approach does not consider glove use since consumers are not
expected to always use gloves, or use gloves constructed with appropriate materials. The consumer
approach factors in time because the duration of product use activities in consumer scenarios have been
better characterized, while duration of dermal exposure times for different occupational activities across
various workplaces are often not known.
2.3.1.5 Manufacture
Process Descriptions
1-BP is produced by reacting n-propyl alcohol with hydrogen bromide and then removing the excess
water that forms in the process (NTP. 2013b). The reaction product may then be distilled, neutralized
with sodium hydrogen carbonate, stored, and packaged (Ichihara et al.. 2004a). The purity of the final
product may range from 96 percent (Li et al.. 2010) to over 99.9 percent (OSHA. 2013a).
Page 85 of 486
-------
The manufacturing process may be either batch or continuous. Based on a site visit in 2013 conducted
by PEC, Icarus Environmental, and OSHA representatives, one major U.S. manufacturer of 1-BP
operates a continuous, closed production process for 24 hours per day and 7 days per week (OSHA.
2013a).
Assessment of Inhalation Exposure Based on Monitoring Data
1-BP exposure monitoring data were identified for one manufacturing facility in the U.S. At this facility,
workers were observed to spend most of their time in a control room monitoring the production process
via a computerized system. QC samples are taken and analyzed inside a laboratory fume hood, and in
some cases, in a nitrogen purge dry box. Product loading is controlled using a computerized system;
smart-hoses and a vent line are used to minimize leaks and to capture vapors generated during loading.
At this facility, employees wear safety glasses, nitrile gloves18, and steel toe shoes when performing
product sampling and laboratory analysis. In addition, operators wear a full chemical suit19 during truck
loading, including a full-face respirator equipped with organic vapor cartridges (OSHA 2013a).
Table 2-7 presents the exposure levels from an OSHA site visit to this facility. The purpose of the site
visit was to collect information on 1-BP production processes, engineering controls, and potential
exposures. OSHA performed personal sampling on one operator during the day shift, one operator
during the night shift, and one laboratory technician; the company also collected simultaneous samples
for result comparison and verification. EPA used the TWA results to assess worker exposures; EPA
assumed the TWA exposures approximate 8-hr TWA because actual sampling time ranged from 429 to
449 minutes (7.2 to 7.5 hour). In the table, the high-end exposure value represents the maximum TWA
exposure among the three workers sampled, and the central tendency value represents the median
exposure. Exposure was highest during truck loading, which occurs once every 24 hours. The operator
wore a full-face respirator during this activity (OSHA 2013a).
Additional monitoring data from a Chinese manufacturing facility were identified during systematic
review and available in Ichihara et al. (Ichihara et al.. 2004a). None of the workers surveyed at this
facility wore PPE, and work practices at this facility may not be representative of U.S. operations.
Therefore, data from this study were not integrated into the assessment.
Table 2-7. Summary of 8-hr 1-BP TWA Exposures (AC, ADC and LADC) for Manufacture Based
on Monitoring Data
Category
Acute and Chron
Exposures (8-Hou
ACi bp, 8-hr twa and
Central tendency
(Median)
ic, Non-Cancer
r TWAs in ppm)
ADCl-BP, 8-hr TWA
High-end (Max)
Chronic, Cane
(PP
LADCi-bi
Central tendency
(Median)
er Exposures
m)
P, 8-hr TWA
High-end (Max)
Data
Points
Confidence
Rating of Air
Concentration
Data
Workera
0.09
0.27
0.04
0.14
3
High
18 Nitrile is not a recommended glove material for protection against 1-BP according to the OSHA/NIOSH Hazard Alert
(OSHA. 2013c).
19 Chemical resistant pants and jacket with hood, steel-toed rubber boots, chemical resistant gloves, and full-face respirator
equipped with organic vapor cartridges.
Page 86 of 486
-------
Source: rOSHA. 2013a)
AC = Acute Concentration; ADC = Average Daily Concentration and LADC = Lifetime Average Daily Concentration,
a - Because OSHA and the company took simultaneous samples, two sets of exposure monitoring data are available for each
worker. For the same worker, EPA used the higher of the two TWA exposure results. For the lab technician and the day shift
operator, EPA used company results (OSHA experienced a pump malfunction while performing sampling on the lab
technician, and OSHA results for the day shift operator were below the reporting limit of 0.007 ppm of OSHA's sampling
and analytical method PV2061). For the night shift operator, EPA used OSHA results. The workers worked 12-hour shifts
but were not exposed to 1-BP for the entire shift; exposure data are available as 8-hr TWA exposures.
Strength, Limitation, and Uncertainty of the Inhalation Exposure Assessment
Exposure is assessed using 1-BP personal breathing zone monitoring data collected at workplaces
directly applicable to this condition of use. The data were obtained from one of only two domestic
manufacturing facilities and were determined to have a "high" confidence rating through EPA's
systematic review process. Specifically, the data were determined to be highly reliable, representative in
geographic scope, and reflective of current operations. The source also provides complete metadata
including sample type, sample duration, and exposure frequency.
The three data points come from a detailed site visit report and consider all sources of exposure at that
manufacturing facility. EPA has a high level of confidence in the assessed exposures based on the
strength of the monitoring data.
2.3.1.6 Import
Process Descriptions
Commodity chemicals such as 1-BP may be imported into the United States in bulk via water, air, land,
and intermodal shipments (Kane. 2015). These shipments take the form of oceangoing chemical tankers,
railcars, tank trucks, and intermodal tank containers. Chemicals shipped in bulk containers may be
repackaged into smaller containers for resale, such as drums or bottles. The type and size of container
will vary depending on customer requirement. In some cases, QC samples may be taken at import sites
for analyses. Some import facilities may only serve as storage and distribution locations, and
repackaging/sampling may not occur at all import facilities.
1-BP may be imported neat or as a component in a formulation. In the 2016 CDR, most companies
reported importing 1-BP at concentrations greater than 90 percent; one company reported importing a
formulation containing 1 to 30 percent 1-BP.
Assessment of Inhalation Exposure Based on Modeling
EPA has not identified exposure monitoring data for import. Therefore, EPA assessed exposure using
the Tank Truck and Railcar Loading and Unloading Release and Inhalation Exposure Model. Based on
data reported in the 2016 CDR, the model assumes 1-BP is present at 30 and 100 percent concentration
in the import formulation for the central tendency and high-end exposure scenario, respectively. The
model provides inhalation exposure estimates to volatile liquid chemicals during outdoor loading and
unloading activities at an industrial facility. The model accounts for the emissions of saturated air
containing the chemical of interest that remains in the loading arm, transfer hose, and related equipment,
and emissions from equipment leaks from processing units such as pumps, seals, and valves. The model
assumes industrial facilities use a vapor recovery system to minimize air emissions, such that vapor
Page 87 of 486
-------
losses from displacement of saturated air inside the container is mitigated by the use of such systems.
See the Supplemental Information on Occupational Exposure Assessment (EPA. 2019f) on model
documentation, including detailed description of the model equations and parameters.
For the central tendency scenario, the model assumes the use of a 12-foot transfer hose with two-inch
diameter, with an average outdoor wind speed of 9 miles per hour (mph). For the high-end scenario, the
model assumes the use of an engineered loading system, such as a loading arm, and that the operation
occurs outdoor with a wind speed of 5 mph. For the purpose of this assessment, loading/unloading event
is assumed to occur once per work shift. Combining published EPA emission factors and engineering
calculations with EPA Mass Balance Inhalation Model (peer reviewed), this model estimates central
tendency and high-end exposure concentrations for chemical unloading scenarios at industrial facilities.
As shown in Table 2-8, the central tendency and high-end exposures are 0.004 ppm and 0.06 ppm as 8-
hr TWA, respectively. The model does not estimate exposure levels for ONUs.
Table 2-8. Summary of 1-BP 8-hr TWA Exposures (AC, ADC and LADC) for Import Based on
Modeling
Category
Acute and Chrc
Exposures (8-Ho
AC 1-BP, 8-hr TWA aU
Central tendency
>nic, Non-Cancer
ur TWAs in ppm)
id ADCl-BP, 8-hr TWA
High-end
Chronic, Cancer
LADCib
Central tendency
Exposures (ppm)
P, 8-hr TWA
High-end
Confidence
Rating of Air
Concentration
Data
Worker
3.83E-3
5.67E-2
1.52E-3
2.91E-2
N/A - Modeled
Data
Strength, Limitation, and Uncertainty of the Inhalation Exposure Assessment
The Tank Truck andRailcar Loading and Unloading Release and Inhalation Exposure Model is used to
estimate exposure. The model uses a combination of published EPA emission factors and engineering
judgement to estimate central tendency and high-end exposures. EPA believes the model exposures are
likely to be representative of exposure associated with bulk container loading. However, the model does
not account for other potential sources of exposure at industrial facilities, such as sampling, equipment
cleaning, and other process activities. The model also assumes only one container is loaded per day,
although larger facilities may have higher product loading frequencies. These model uncertainties could
result in an underestimate of the worker exposure. Based on reasonably available information above,
EPA has a medium level of confidence in the assessed exposure.
2.3.1.7 Processing as a Reactant
Process Descriptions
Processing as a reactant or intermediate is the use of 1-BP as a raw material in the production of another
chemical, in which 1-BP is reacted and consumed. According to the 2016 CDR, 1-BP is used as an
intermediate20 in the production of other organic chemicals, inorganic chemicals, pesticides, fertilizers,
211 Pharmaceuticals was erroneously included in the description for this condition of use within the draft risk evaluation.
Therefore, it has been removed from the final risk evaluation.
Page 88 of 486
-------
and other agricultural chemicals. The volume of these uses from CDR are CBI (Enviro Tech
International. 2017; HSIA. 2010).
Assessment of Inhalation Exposure Based on Modeling
See Section 2.3.1.6 for the assessment of worker exposure from chemical unloading activities. At
industrial facilities, workers are potentially exposed when unloading 1-BP from transport containers into
intermediate storage tanks and process vessels. Workers may be exposed via inhalation of vapor or via
dermal contact with liquids while connecting and disconnecting hoses and transfer lines. EPA assumes
the exposure sources, routes, and exposure levels are similar to those at an import facility. The exposure
results are presented in Table 2-9.
Table 2-9. Summary of 1-BP 8-hr TWA Exposures (AC, ADC and LADC) for Processing as a
Reactant Based on Modeling
Category
Acute and Chrc
Exposures (8-Ho
AC 1-BP, 8-hr TWA aU
Central tendency
>nic, Non-Cancer
ur TWAs in ppm)
id ADCl-BP, 8-hr TWA
High-end
Chronic, Cancer
LADCib
Central tendency
Exposures (ppm)
\ 8-hr TWA
High-end
Confidence
Rating of Air
Concentration
Data
Worker
3.83E-3
5.67E-2
1.52E-3
2.91E-2
N/A - Modeled
Data
Strength, Limitation, and Uncertainty of the Inhalation Exposure Assessment
The Tank Truck andRailcar Loading and Unloading Release and Inhalation Exposure Model is used to
estimate exposure. The model uses a combination of published EPA emission factors and engineering
judgement to estimate central tendency and high-end exposures. EPA believes the model exposures are
likely to be representative of exposure associated with bulk container loading. However, this activity
may be only a small part of the worker's day. The model does not account for other potential sources of
exposure at industrial facilities, such as sampling, equipment cleaning, and other process activities that
can contribute to a worker's overall 8-hr daily exposure. The model also assumes only one container is
loaded per day, although larger facilities may have higher product loading frequencies. These model
uncertainties could result in an underestimate of the worker 8-hr exposure. Based on reasonably
available information above, EPA has a medium level of confidence in the assessed exposure.
2.3.1.8 Processing - Incorporation into Formulation, Mixture, or Reaction Product
Process Descriptions
After manufacture, 1-BP may be supplied directly to end-users, or may be incorporated into various
products and formulations at varying concentrations for further distribution. Incorporation into a
formulation, mixture, or reaction product refers to the process of mixing or blending several raw
materials to obtain a single product or preparation. For example, formulators may add stabilizing
packages to 1-BP for specialized vapor degreasing uses (Enviro Tech International 2017). or mix 1-BP
with other additives to formulate adhesives, sealants, and other products. The specific worker activity to
unload 1-BP into the system, the type of formulation equipment used, the exact production schedule, and
presence of engineering control will likely differ among various formulation facilities.
Page 89 of 486
-------
Assessment of Inhalation Exposure Based on Monitoring Data
For formulation of 1-BP into products, EPA assessed exposure using personal air monitoring data from a
formulation facility submitted by Enviro Tech. The facility is dedicated to the production of 1-BP based
products; a batch of product containing 80 to 96 percent 1-BP is produced during a single eight-hour
shift per year, and production takes place twice per weeks for 50 weeks per year in a closed system with
mechanized filling operations. Table 2-10 presents the central tendency and high-end exposure levels for
employees at this facility. The worker exposure level represents employee exposure when working as
the mixing room operator; the mixing room is where all mixing, decanting, and filling operations occur.
Employees at this facility work once during the work week as the mixing room operator, and performs
other work for the remainder of the week. Exposure levels for occupational non-user represent employee
exposure when performing other job duties, primarily in the warehouse, storage, office, areas of the
facility where they do not directly handle 1-BP (Enviro Tech International 2020).
In a separate study, Hanley et al. (Hanlev et al.. 2010) measured exposure at an adhesive manufacturing
facility. The study did not provide detailed data to allow determination of 50th and 95th percentile
exposures, but stated that the geometric mean full-shift (8 to 10 hour) TWA measurement was 3.79 ppm
for those who handled 1-BP products (workers), and 0.33 ppm for those who did not use 1-BP (i.e.,
ONUs). The maximum exposure value was 18.9 ppm TWA for those who directly used 1-BP, and 1.59
ppm TWA for those who did not use 1-BP. This facility does not have local exhaust ventilation, but uses
high volume general dilution ventilation to provide directional air flow in the production area (Hanlev et
al.. 2010).
Table 2-10. Summary of 1-BP 8-hr TWA Exposures (AC, ADC and LADC) for
Processing/Formulation Based on Monitoring Data
Category
Acute and Chronic, Non-Cancer
Exposures (8-Hour TWAs in ppm)
ACl-BP, 8-hr TWA and ADCl-BP, 8-hr TWA
Central tendency | High-end
Chronic, Cancer Exposures
(ppm)
LADCl-BP, 8-hr TWA
Central tendency | High-end
Data
Points
Confidence
Rating of Air
Concentration
Data
Worker
7.20
2.86
1
High
ONU
0.16
0.28
0.06
0.14
10
Source: (Enviro Tech International. 2020)
Strength, Limitation, and Uncertainty of the Inhalation Exposure Assessment
Exposure is assessed using 1-BP personal breathing zone monitoring data collected at one formulation
facility. Although the data have a high confidence rating and are directly applicable to this condition of
use, the data may not be representative of exposures across the range of facilities that formulate products
containing 1-BP. Based on reasonably available information above, EPA has a medium level of
confidence in the assessed exposure.
2.3.1.9 Processing - Incorporation into Articles
Process Descriptions
According to EPA's Use Dossier, 1-BP is present at less than 5 percent concentration in the
THERMAX™ brand insulation manufactured by Dow Chemical (U.S. EPA. 2017c). THERMAX™ is a
Page 90 of 486
-------
polyisocyanurate rigid board insulation for interior and exterior applications, and can be used on walls,
ceilings, roofs, and crawl spaces in commercial and residential buildings. The product is marketed to
have superior durability and fire performance over generic polyisocyanurate insulations.21 EPA does not
have information on the exact process for producing THERMAX™ and the function of 1-BP in the
insulation material (DOW. 2018).
Assessment of Inhalation Exposure Based on Modeling
EPA did not find monitoring data for this condition of use. As such, EPA modeled exposure using the
Tank Truck and Railcar Loading and Unloading Release and Inhalation Exposure Model. The model
provides estimates of high-end and central tendency exposure concentration for a chemical unloading
scenario. See Section 2.3.1.6 for the assessment of worker exposure from chemical unloading activities.
The exposure results are presented in Table 2-11.
Table 2-11. Summary of 1-BP 8-hr TWA Exposures (AC, ADC and LADC) for Processing -
Incorporation into Articles Based on Modeling
Category
Acute and Chrc
Exposures (8-Ho
AC 1-BP, 8-hr TWA aU
Central tendency
>nic, Non-Cancer
ur TWAs in ppm)
1(1 ADCl-BP, 8-hr TWA
High-end
Chronic, Cancer
LADCib
Central tendency
Exposures (ppm)
P, 8-hr TWA
High-end
Confidence
Rating of Air
Concentration
Data
Worker
3.83E-3
5.67E-2
1.52E-3
2.91E-2
N/A - Modeled
Data
Strength, Limitation, and Uncertainty of the Inhalation Exposure Assessment
The Tank Truck and Railcar Loading and Unloading Release and Inhalation Exposure Model is used to
estimate exposure. The model uses a combination of published EPA emission factors and engineering
judgment to estimate central tendency and high-end exposures. EPA believes the model exposures are
likely to be representative of exposure associated with bulk container loading. However, the model does
not account for other potential sources of exposure at industrial facilities, such as sampling, equipment
cleaning, and other process activities. The model also assumes only one container is loaded per day,
although larger facilities may have higher product loading frequencies. These model uncertainties could
result in an underestimate of the worker exposure. Based on reasonably available information above,
EPA has a medium level of confidence in the assessed exposure.
2.3.1.10 Repackaging
Process Descriptions
Chemicals shipped in bulk containers may be repackaged into smaller containers for resale, such as
drums or bottles. The type and size of container will vary depending on customer requirement. In some
cases, QC samples may be taken at repackaging sites for analyses. Repackaging could occur for both
21 https://www.dow.com/en-us/products/thermaxbrandinsulation#sort=%40gtitle%20ascending
Page 91 of 486
-------
domestic and imported shipments of 1-BP; repackaging activities that occur at import facilities are
addressed in Section 2.3.1.6.
Assessment of Inhalation Exposure Based on Modeling
EPA has not identified exposure monitoring data for repackaging. Therefore, EPA assessed exposure
using the Tank Truck and Railcar Loading and Unloading Release and Inhalation Exposure Model. As
shown in Table 2-12, the central tendency and high-end exposures are 0.004 ppm and 0.06 ppm as 8-hr
TWA, respectively. The model does not estimate exposure levels for ONUs.
Table 2-12. Summary of 1-BP 8-hr TWA Exposures (AC, ADC and LADC) for Repackaging
Based on Modeling
Category
Acute and Chrc
Exposures (8-Ho
AC 1-BP, 8-hr TWA aU
Central tendency
>nic, Non-Cancer
ur TWAs in ppm)
id ADCl-BP, 8-hr TWA
High-end
Chronic, Cancer
LADCib
Central tendency
Exposures (ppm)
P, 8-hr TWA
High-end
Confidence
Rating of Air
Concentration
Data
Worker
3.83E-3
5.67E-2
1.52E-3
2.91E-2
N/A - Modeled
Data
Strength, Limitation, and Uncertainty of the Inhalation Exposure Assessment
The Tank Truck and Railcar Loading and Unloading Release and Inhalation Exposure Model is used to
estimate exposure. The model uses a combination of published EPA emission factors and engineering
judgement to estimate central tendency and high-end exposures. EPA believes the model exposures are
likely to be representative of exposure associated with bulk container loading. However, the model does
not account for other potential sources of exposure at industrial facilities, such as sampling, equipment
cleaning, and other process activities. The model also assumes only one container is loaded per day,
although larger facilities may have higher product loading frequencies. These model uncertainties could
result in an underestimate of the worker exposure. Based on reasonably available information above,
EPA has a medium level of confidence in the assessed exposure.
2.3.1.11 Batch Vapor Degreaser (Open-Top)
Process Descriptions
Vapor degreasing is a process used to remove dirt, grease, and surface contaminants in a variety of
industries. 1-BP is often used to replace chlorinated solvents, especially in applications where
flammability is a concern (CRC Industries Inc.. 2017). 1-BP is also desirable because of its low
corrosivity, compatibility with many metals, and suitability for use in most modern vapor degreasing
equipment. Vapor degreasing may take place in batches or as part of an in-line (i.e., continuous) system.
In batch machines, each load (parts or baskets of parts) is loaded into the machine after the previous load
is completed. With in-line systems, parts are continuously loaded into and through the vapor degreasing
equipment as well as the subsequent drying steps. Vapor degreasing equipment can generally be
categorized into one of the three categories: (1) batch vapor degreasers, (2) conveyorized vapor
degreasers and (3) web vapor degreasers.
Page 92 of 486
-------
In batch open-top vapor degreasers (OTVDs), a vapor cleaning zone is created by heating and
volatilizing the liquid solvent in the OTVD. Workers manually load or unload fabricated parts directly
into or out of the vapor cleaning zone. The tank usually has chillers along the side of the tank to prevent
losses of the solvent to the air. However, these chillers are not able to eliminate emissions, and
throughout the degreasing process emissions of the solvent to air can occur. Additionally, the cost of
replacing solvent lost to emissions can be expensive (NEWMOA. 2001). The use of 1-BP in OTVD has
been previously described in EPA's 2016 Draft Risk Assessment (U.S. EPA 2016c).
OTVDs with enclosures operate the same as standard OTVDs except that the OTVD is enclosed on all
sides during degreasing. The enclosure is opened and closed to add or remove parts to/from the machine,
and solvent is exposed to the air when the cover is open. Enclosed OTVDs may be vented directly to the
atmosphere or first vented to an external carbon filter and then to the atmosphere (U.S. EPA; ICF
Consulting. 2004). Figure 2-1 illustrates an OTVD with an enclosure. The dotted lines in Figure 2-1
represent the optional carbon filter that may or may not be used with an enclosed OTVD.
J
Loading/
unloading
lock
Boiling su
Heat Sou
np-
ce-
[
Carbon Filter
Vapor Zone
Z
•vent
¦s
]
]/W,
Condensing Coils
Wate Jacket
er Separator
Figure 2-1. Open-Top Vapor Degreaser with Enclosure
Assessment of Inhalation Exposure Based on Monitoring Data
Table 2-13 summarizes the 1-BP exposure data for vapor degreasing operations. EPA obtained exposure
monitoring data from several sources, including journal articles, public comments, NIOSH Health
Hazard Evaluations (HHEs), the OSHA Chemical Exposure Health Data (CEHD) database, and data
submitted to EPA SNAP program. NIOSH HHEs are conducted at the request of employees, employers,
or union officials, and provide information on existing and potential hazards present in the workplaces
evaluated. OSHA CEHD are workplace monitoring data from OSHA inspections; EPA SNAP program
data are collected as part of EPA's effort to identify substitutes for ozone-depleting substances. Some of
these data, such as monitoring data conducted during OSHA inspections, are not intended to be
representative of typical exposure levels.
Page 93 of 486
-------
Data from these sources cover exposure at a variety of industries that conduct vapor degreasing,
including telecommunication device manufacturing, aerospace parts manufacturing, electronics parts
manufacturing, helicopter transmission manufacturing, hydraulic power control component
manufacturing, metal product fabrication, optical prism and assembly, and printed circuit board
manufacturing. It should be noted that sources that only contain a statistical summary of worker
exposure monitoring, but exclude the detailed monitoring results, are not included in EPA's analysis
below.
Most of the gathered data were for batch open-top vapor degreasers, except for data from OSHA
(OSHA. 2019. 2013b) and EPA SNAP program, where the type of degreaser is typically not specified.
EPA included these data in the analysis despite uncertainty in the degreaser type.
Monitoring data show exposure levels can vary widely depending on several factors, including facility
ventilation, degreaser design (e.g., freeboard ratio), or the presence of an enclosure. The 2016 Draft Risk
Assessment (U.S. EPA 2016c) previously categorized data as either pre- or post-Engineering Control.
After further evaluation, EPA removed these categories because EPA determined there is insufficient
information on engineering controls at all facilities to accurately characterize the dataset.
EPA defined a vapor degreasing "worker" as an employee who operates or performs maintenance tasks
on the degreaser, such as draining, cleaning, and charging the degreaser bath tank. EPA defined
"occupational non-user" as an employee who does not directly handle 1-BP but performs work in the
surrounding area. Some data sources do not describe their work activities in detail, and the exact
proximity of these occupational non-users to the degreaser is unknown. As shown in the table, the 50th
and 95th percentile exposure levels for workers are 6.70 ppm and 49.3 ppm as 8-hr TWA, respectively.
For occupational non-users, the 50th and 95th percentile exposure levels are below 1 ppm as 8-hr TWA.
Table 2-13. Summary of 1-BP 8-hr TWA Exposures (AC, ADC and LADC) for Vapor Degreaser
Based on Monitoring Data
Category
Acute and Chron
Exposures (8-Hou
ACi bp, 8-hr twa and
50th Percentile
ic, Non-Cancer
r TWAs in ppm)
ADCl-BP, 8-hr TWA
95th Percentile
Chronic, Cane
(PP
LADCi-bi
50th Percentile
er Exposures
m)
P, 8-hr TWA
95th Percentile
Data
Points
Confidence
Rating of Air
Concentration
Data
Worker
6.70
49.3
2.66
25.3
155
Medium -
High
ONU
0.10
0.46
0.04
0.24
75
Source: (OSHA. 2019. 2013b: U.S. EPA. 2006b: Reh and Nemhauser. 2001) (Miller. 2019)
Assessment of Inhalation Exposure Based on Modeling
Figure 2-2 illustrates the near-field / far-field model that can be applied to vapor degreasing (AIHA.
2009). As the figure shows, volatile 1-BP vapors evaporate into the near-field, resulting in worker
exposures at a concentration Cnf. The concentration is directly proportional to the evaporation rate of 1-
BP, G, into the near-field, whose volume is denoted by Vnf. The ventilation rate for the near-field zone
(Qnf) determines how quickly 1-BP dissipates into the far-field, resulting in occupational non-user
exposures to 1-BP at a concentration Cff. Vff denotes the volume of the far-field space into which the 1-
BP dissipates out of the near-field. EPA assumes the far-field volume (Vff) ranges from 300 m3 (10,594
ft3) to 2,000 m3 (70,629 ft3) for degreasing facilities (Von Grote et al.. 2003). The ventilation rate for the
Page 94 of 486
-------
surroundings, denoted by Qff, determines how quickly 1-BP dissipates out of the surrounding space and
into the outside air. See Supplemental Information on Occupational Exposure Assessment (EPA. 2019f)
for the model equations, model parameters, parameter distributions, and associated assumptions.
Far-Field
Figure 2-2. Schematic of the Near-Field/Far-Field Model for Vapor Degreasing
To estimate the 1-BP vapor generation rate, the model references an emission factor developed by the
California Air Resources Board (CARB) for the California Solvent Cleaning Emissions Inventories
(CARB. 2011). CARB surveyed facilities that conduct solvent cleaning operations and gathered site-
specific information for 213 facilities. CARB estimated a 1-BP emission factor averaging 10.43
lb/employee-yr, with a standard deviation of 17.24 lb/employee-yr, where the basis is the total number
of employees at a facility. The majority of 1-BP emissions were attributed to the vapor degreasing
category.
The "vapor degreasing" category in CARB's study includes the batch-loaded vapor degreaser, aerosol
surface preparation process, and aerosol cleaning process. It is not known what percentage, if any, of the
1-BP emission factor is derived from aerosol applications. This modeling approach assumes the 1-BP
emission factor is entirely attributed to vapor degreasing applications. The emission factor is expected to
represent emissions from batch-loaded degreasers used in California at the time of study. It is not known
whether these are specifically open-top batch degreasers, although open-top is expected to be the most
common design. The CARB survey data did not include emissions for conveyorized vapor degreasers.
Page 95 of 486
-------
The CARB emission factor is then combined with U.S. employment data for vapor degreasing industry
sectors from the Economic Census.22 The 2016 1-BP draft Risk Assessment (U.S. EPA. 2016c)
identified 78 NAICS industry codes that are applicable to vapor degreasing. For these industry codes,
the Census data set indicates a minimum industry average of 8 employees per site, with a 50th percentile
and 90th percentile of 25 and 61 employees per site, respectively. A lognormal distribution is applied to
the Census data set to model the distribution of the industry-average number of employees per site for
the NAICS codes applicable to vapor degreasing.
These nationwide Census employment data are comparable to the 2008 California employment data
cited in CARB's study. According to the CARB study, approximately 90 percent of solvent cleaning
facilities in California had less than 50 employees (whereas the national Census data estimate 90 percent
of facilities have less than or equal to 61 employees). Census data report an average number of
employees per site for each NAICS code. The number of employees for each individual site within each
NAICS code is not reported. Therefore, the distribution EPA calculated represents a population of
average facility size for each NAICS code, and not the population of individual facility sizes over all
NAICS codes.
The vapor generation rate, G (kg/unit-hr), is calculated in-situ within the model, as follows:
Equation 2-1. Equation for Calculating Vapor Degreasing Vapor Generation Rate
G = EF x EMP / (2.20462 x OH x OD x U)
Where
EF = emission factor (lb/employee-yr)
EMP = Number of employees (employee/site)
OH = Operating hours per day (hr/day)
OD = Operating days per year (day/yr)
U = Number of degreasing units (unit/site)
2.20462 = Unit conversion from lb to kg (lb/kg)
Batch degreasers are assumed to operate between two and 24 hours per day, based on NEI data on the
reported operating hours for OTVD using TCE. EPA performed a Monte Carlo simulation with 100,000
iterations and the Latin Hypercube sampling method in @Risk23 to calculate 8-hour TWA near-field and
far-field exposure concentrations. Near-field exposure represents exposure concentrations for workers
who directly operate the vapor degreasing equipment, whereas far-field exposure represents exposure
22 For the purpose of modeling, EPA used data from the 2007 Economic Census for the vapor degreasing NAICS codes as
identified in the TCE RA (U.S. EPA. 2014c). The 2012 Economic Census did not have employment data (average number of
employees per establishment) for all vapor degreasing NAICS codes of interest.
23 A risk analysis software tool (Microsoft Excel add-in) using Monte Carlo simulation
Page 96 of 486
-------
concentrations for occupational non-users {i.e., workers in the surrounding area who do not handle the
degreasing equipment). Table 2-14 presents a statistical summary of the exposure modeling results.
These exposure estimates represent modeled exposures for the workers and occupational non-users. For
workers, the baseline (pre-engineering control) 50th percentile exposure is 1.89 ppm 8-hr TWA, with a
95th percentile of 23.9 ppm 8-hr TWA. Compared to literature studies:
• Hanley et al. (2010) reported a geometric mean of 2.63 ppm 8-hr TWA exposure with a range of
0.078 to 21.4 ppm 8-hr TWA among 44 samples;
• NIOSH (Reh and Nemhauser. 2001) reported a range of 0.01 to 0.63 ppm 8-hr TWA among 20
samples;
• A 2003 EPA analysis suggested that 87 percent of the samples were less than 25 ppm 8-hr TWA
among 500 samples at vapor degreasing facilities (U.S. EPA. 2003).
The modeled mean near-field exposure is found to be generally comparable to the exposures reported in
literature. For occupational non-users, the modeled far-field exposure has a 50th percentile value of
0.99 ppm and a 95th percentile of 13.5 ppm 8-hr TWA. These modeled far-field results are somewhat
higher than reported literature values. (Hanley et al.. 2010) reported workers away from the degreasers
are exposed at concentrations of 0.077 to 1.69 ppm 8-hr TWA, with a geometric mean of 0.308 ppm 8-
hr TWA. The modeled exposures represent the potential exposure associated with batch-loaded
degreasers, which could include both OTVD and batch-loaded, closed-loop vapor degreasers.
The model also presents a "post-Engineering Control" (post-EC) scenario by applying a 90 percent
emission reduction factor to the baseline, pre-EC scenario. The estimate is based on a Wadden et al.
(1989) study, which indicates a LEV system for an open-top vapor degreaser (lateral exhaust hoods
installed on two sides of the tank) can be 90 percent effective (Wadden et al.. 1989). The study covered
only reductions in degreaser machine emissions due to LEV and did not address other sources of
emissions such as dragout, fresh and waste solvent storage and handling. Furthermore, a caveat in the
study is that most LEV likely do not achieve ACGIH design exhaust flow rates, indicating that the
emission reductions in many units may not be optimized. Therefore, using this factor likely
overestimates control technology efficiency, and underestimates exposures. Actual exposure reductions
from added engineering controls can be highly variable.
Page 97 of 486
-------
Table 2-14. Summary of 1-BP 8-hr TWA Exposures (AC, ADC and LADC) for Batch Vapor
Degreaser (Open-Top) Based on Modeling
Category
Acute and Chronic, Non-Cancer
Exposures (8-Hour TWAs in ppm)
AC1-BP, 8-hr TWA and ADCl-BP, 8-hr TWA
50th Percentile 95th Percentile
Chronic, Cancer Exposures (ppm)
LADCl-BP, 8-hr TWA
50th Percentile 95th Percentile
Confidence
Rating of Air
Concentration
Data
Workers (Near-Field)
Pre EC
1.89
23.9
0.70
9.19
N/A-
Modeled Data
Post EC 90%
0.19
2.39
0.07
0.92
Occupational non-users (Far-Field)
Pre EC
0.99
13.5
0.37
5.23
N/A-
Modeled Data
Post EC 90%
0.10
1.35
0.04
0.52
Pre-EC: refers to modeling where no reduction due to engineering controls was assumed
Post-EC: refers to modeling where engineering controls with 90% efficiency were implemented. The percent effectiveness is
applied to the pre-EC exposure concentration to calculate post-EC exposure.
Strength, Limitation, and Uncertainty of the Inhalation Exposure Assessment
Exposure is assessed using 1-BP personal breathing zone monitoring data from several different sources,
with confidence rating of the data ranging from medium to high, as determined through EPA's
systematic review process. Some of the data sources do not clearly specify whether the vapor degreaser
is a batch, open-top system or another system. Because OTVDs typically have the highest emissions
among all vapor degreasers, the inclusion of data for other degreaser types may underestimate exposure
for this condition of use.
The exposure data are supplemented with near-fteld/far-fteld exposure modeling using a Monte Carlo
analysis, which incorporates variability in the model input parameters. This model was peer reviewed as
part of the 2016 1-BP draft Risk Assessment (U.S. EPA 2016c). Although there is some uncertainty on
the CARB emission factor used in the model and whether the factor represents emissions exclusively for
batch open-top systems, the model results are in general agreement with monitoring data. Based on
reasonably available information, EPA has a high level of confidence in the assessed exposure for this
condition of use.
2.3.1.12 Batch Vapor Degreaser (Closed-Loop)
Process Descriptions
In closed-loop degreasers, parts are placed into a basket, which is then placed into an airtight work
chamber. The door is closed, and solvent vapors are sprayed onto the parts. Solvent can also be
introduced to the parts as a liquid spray or liquid immersion. When cleaning is complete, vapors are
exhausted from the chamber and circulated over a cooling coil where the vapors are condensed and
recovered. The parts are dried by forced hot air. Air is circulated through the chamber and residual
solvent vapors are captured by carbon adsorption. The door is opened when the residual solvent vapor
concentration has reached a specified level (Kanegsberg and Kanegsberg. 2011). Figure 2-3 illustrates a
standard closed-loop vapor degreasing system.
Page 98 of 486
-------
Vent
Solvent Tank(s)
Distillation
Solvent Abatement Loop
Working Chamber
Workload
Solvent Sump
Refrigeration
Electric Heat
Figure 2-3. Closed-loop/Vacuum vapor Degreaser
Airless degreasing systems are also sealed, closed-loop systems, but remove air at some point of the
degreasing process. Removing air typically takes the form of drawing vacuum but could also include
purging air with nitrogen at some point of the process (in contrast to drawing vacuum, a nitrogen purge
operates at a slightly positive pressure). In airless degreasing systems with vacuum drying only, the
cleaning stage works similarly as with the airtight closed-loop degreaser. However, a vacuum is
generated during the drying stage, typically below 5 torr (5 mmHg). The vacuum dries the parts and a
vapor recovery system captures the vapors (Kanegsberg and Kanegsberg. 2011; ERG. 2001;
NEWMOA. 2001).
Airless vacuum-to-vacuum degreasers are true "airless" systems because the entire cycle is operated
under vacuum. Typically, parts are placed into the chamber, the chamber sealed, and then vacuum
drawn within the chamber. The typical solvent cleaning process is a hot solvent vapor spray. The
introduction of vapors in the vacuum chamber raises the pressure in the chamber. The parts are dried by
again drawing vacuum in the chamber. Solvent vapors are recovered through compression and cooling.
An air purge then purges residual vapors over an optional carbon adsorber and through a vent. Air is
then introduced in the chamber to return the chamber to atmospheric pressure before the chamber is
opened (Durkee. 2014; NEWMOA 2001). The general design of vacuum vapor degreasers and airless
vacuum degreasers is similar as illustrated in Figure 2-3 for closed-loop systems except that the work
chamber is under vacuum during various stages of the cleaning process.
Assessment of Inhalation Exposure Based on Modeling
There are no 1-BP monitoring data specific to closed-loop degreasers. A NEWMOA study states air
emissions can be reduced by 98 percent or more when a closed-loop degreaser is used instead of an
open-top vapor degreaser (NEWMOA. 2001). This reduction factor is applied to the vapor degreasing
model results presented in Section 2.3.1.11 to estimate exposure to batch closed-loop vapor degreasers.
Page 99 of 486
-------
The approach assumes the CARB emission factor primarily represents emissions from OTVDs, rather
than other types of batch-loaded degreasers.
Table 2-15 presents the exposure model results for batch closed-loop vapor degreasers. For workers, the
50th and 95th percentile exposure levels are 0.04 ppm and 0.48 ppm as 8-hr TWA. For occupational non-
users, the 50th and 95th percentile exposure levels are 0.02 ppm and 0.27 ppm as 8-hr TWA, respectively.
Table 2-15. Summary of 1-BP 8-hr TWA Exposures (AC, ADC and LADC) for Batch Closed-
Loop Vapor Degreasing Based on Modeling
Category
Acute and Chr
Exposures (8-H<
ACl-BP, 8-hr TWA a
50th Percentile
onic, Non-Cancer
)ur TWAs in ppm)
nd ADCl-BP, 8-hr TWA
95th Percentile
Chronic, Cancer
LADCi-
50th Percentile
Exposures (ppm)
BP, 8-hr TWA
95th Percentile
Confidence
Rating of Air
Concentration
Data
Worker
0.04
0.48
0.01
0.18
N/A-
Modeled Data
ONU
0.02
0.27
0.01
0.10
Strength, Limitation, and Uncertainty of the Inhalation Exposure Assessment
For this condition of use, EPA did not identify any exposure monitoring data. Exposure is assessed using
the OTVD model and by assuming 98 percent exposure reduction when switching from open-top to
closed-loop batch vapor degreasers. The model incorporates variability in the input parameters through a
Monte Carlo approach, and the model was peer reviewed in 2016. However, the representativeness of
the exposure reduction factor used in the model is not known, as actual exposure will likely differ
depending on the specific equipment design and work practices. In addition, this model uses the CARB
emission factor for batch-loaded degreasers to estimate average baseline emissions from open-top vapor
degreasers, which could result in an underestimate. Based on reasonably available information, EPA has
a medium level of confidence in the assessed exposure for this condition of use.
2.3.1.13 In-line Vapor Degreaser (Conveyorized)
Process Descriptions
In conveyorized systems, an automated parts handling system, typically a conveyor, continuously loads
parts into and through the vapor degreasing equipment and the subsequent drying steps. Conveyorized
degreasing systems are usually fully enclosed except for the conveyor inlet and outlet portals.
Conveyorized degreasers are likely used in shops where large number of parts need to be cleaned. There
are seven major types of conveyorized degreasers: monorail degreasers; cross-rod degreasers; vibra
degreasers; ferris wheel degreasers; belt degreasers; strip degreasers; and circuit board degreasers (U.S.
EPA. 1977). See Supplemental Information on Occupational Exposure Assessment (EPA. 2019f) for
detailed description of each type of conveyorized degreaser.
Continuous web cleaning machines are a subset of conveyorized degreasers but differ in that they are
specifically designed for cleaning parts that are coiled or on spools such as films, wires, and metal strips
(Kanegsberg and Kanegsberg. 2011; U.S. EPA. 2006a). In continuous web degreasers, parts are
uncoiled and loaded onto rollers that transport the parts through the cleaning and drying zones at speeds
Page 100 of 486
-------
greater than 11 feet per minute (U.S. EPA. 2006a). The parts are then recoiled or cut after exiting the
cleaning machine (Kanegsberg and Kanegsberg. 2011; U.S. EPA. 2006a).
Assessment of Inhalation Exposure
There are no monitoring data specific to conveyorized degreasers that use 1-BP. Additionally, there is
not sufficient data to model exposure to 1-BP from these degreasers.
The 2014 NEI contains emission data for dichloromethane (DCM), perchloroethylene (PERC), and
trichloroethylene (TCE). Based on comparison of NEI data for OTVD and conveyorized vapor
degreasers, emissions from conveyorized vapor degreasers are generally similar to that from OTVDs. As
such, EPA assumed the associated 1-BP worker exposure for conveyorized degreasers may be similar to
the exposure levels presented in Section 2.3.1.11 Batch Vapor Degreaser (Open-Top).
2.3.1.14 Cold Cleaner
Process Descriptions
Cold cleaners are non-boiling solvent degreasing units. Cold cleaning operations include spraying,
brushing, flushing, and immersion. Figure 2-4 shows the design of a typical batch-loaded, maintenance
cold cleaner, where dirty parts are cleaned manually by spraying and then soaking in the tank. After
cleaning, the parts are either suspended over the tank to drain or are placed on an external rack that
routes the drained solvent back into the cleaner. Batch manufacturing cold cleaners could vary widely,
but have two basic equipment designs: the simple spray sink and the dip tank. The dip tank design
typically provides better cleaning through immersion, and often involves an immersion tank equipped
with agitation (U.S. EPA. 1981). Emissions from batch cold cleaning machines typically result from (1)
evaporation of the solvent from the solvent-to-air interface, (2) "carry out" of excess solvent on cleaned
parts, and (3) evaporative losses of the solvent during filling and draining of the machine (U.S. EPA.
2006a). Emissions from cold in-line (conveyorized) cleaning machines result from the same
mechanisms, but with emission points only at the parts entry and exit ports (U.S. EPA. 2006a).
Page 101 of 486
-------
Spray
Pump
Figure 2-4. Typical Batch-Loaded, Maintenance Cold Cleaner (U.S. EPA, 1981)
Assessment of Inhalation Exposure Based on Monitoring Data
The general worker activities for cold cleaning include placing the parts that require cleaning into a
vessel. The vessel is usually something that will hold the parts but not the liquid solvent (i.e., a wire
basket). The vessel is then lowered into the machine, where the parts could be sprayed, and then
completely immersed in the solvent. After a short time, the vessel is removed from the solvent and
allowed to drip or air dry. Depending on the industry and/or company, these operations may be
performed manually (i.e., by hand) or mechanically. Sometimes parts require more extensive cleaning;
in these cases, additional cleaning is performed including directly spraying, agitation, wiping or
brushing (Reh and Nemhauser. 2001; U.S. EPA. 1997).
Table 2-16 presents OSHA CEHD for two facilities. The first facility uses 1-BP to clean parts in an
immersion process in an area with general ventilation. The second facility uses 1-BP in a degreasing
tank equipped with a spray nozzle. The degreasing operation is conducted in an area with local exhaust
ventilation. Based on the available process description, EPA assumes these facilities operate a cold
cleaner, even though the equipment is not described in detail in the OSHA CEHD. For workers, only
five data points are available - the median and maximum exposures are 4.30 ppm and 7.40 ppm 8-hr
TWA, respectively, from the available dataset. For occupational non-users, the exposure value is based
on a single data point for a Chemical Safety and Health Officer (CSHO), who is an official from OSHA
or a state plan occupational safety and health program. The exposure for this individual measured 2.60
ppm 8-hr TWA. EPA presents this data point as the potential exposure level for an occupational non-
user; however, the exposure level may not be representative because the CSHO is not regularly present
in the production area. It should be further noted that CEHD are obtained from OSHA inspections, and
not intended to be representative of typical worker exposure.
Page 102 of 486
-------
Table 2-16. Summary of 1-BP Inhalation Exposure Monitoring Data for Cold Cleaner
Category
Acute and Chron
Exposures (8-Hou
ACi bp, 8-hr twa and
Central tendency
ic, Non-Cancer
r TWAs in ppm)
ADCl-BP, 8-hr TWA
High-end (Max)
Chronic, Cane
(PP
LADCi-bi
Central tendency
er Exposures
m)
P, 8-hr TWA
High-end (Max)
Data
Points
Confidence
Rating of Air
Concentration
Data
Worker
4.30
7.40
1.71
3.79
5
High
ONU
2.60
1.03
1.33
1
Source: (OSHA. 2013b. d).
Assessment of Inhalation Exposure Based on Modeling
Detailed description of the Cold Cleaning modeling approach is provided in the Supplemental
Information on Occupational Exposure Assessment (EPA. 2019f). The EPA AP-42. Compilation of Air
Emissions Factors contains emission factors and process information developed and compiled from
source test data, material balance studies, and engineering estimates (U.S. EPA. 1981). AP-42 Chapter
4.6 provides generic, non-methane VOC emission factors for several solvent cleaning operations,
including cold cleaning and vapor degreasing. These emission factors suggest that cold cleaning
emissions range from 3.2 to 57.1 percent of the emissions from a traditional open-top vapor degreaser
(U.S. EPA. 1981). It is not known whether the emission factors derived using VOC data would be
representative of 1-BP emissions, or whether the emission reduction when switching from vapor
degreasing to cold cleaning would be similar across different chemicals. To model exposures during 1-
BP cold cleaning, an exposure reduction factor, RF, with uniform distribution from 0.032 to 0.571 is
applied to the vapor generation rate in the vapor degreasing model.
Figure 2-5 presents the model approach for cold cleaning. Except for the exposure reduction factor, the
model approach and input parameters for cold cleaning are identical to those previously presented for
batch vapor degreasing. EPA performed a Monte Carlo simulation with 100,000 iterations and the Latin
Hypercube sampling method in @Risk to estimate 8-hr TWA near-field and far-field exposures, acute
exposures, ADCs, and LADCs. The cold cleaning model approach and the underlying data used (i.e.,
EPA AP-42) do not differentiate between a spray versus immersion cold cleaner.
Page 103 of 486
-------
NF
Far-Field
Near-Field
NF
Volatile Source
* Qi
NF
Figure 2-5. The Near-Field/Far-field Model for Cold Cleaning Scenario
Table 2-17 presents a statistical summary of the inhalation exposure modeling results. For workers, the
50th and 95th percentile exposures are 0.55 ppm and 11.91 ppm 8-hr TWA. For occupational non-users,
the 50th and 95th percentile exposures are 0.29 ppm and 6.83 ppm 8-hr TWA. The model exposure levels
are in good agreement with monitoring data.
Table 2-17. Summary of 1-BP 8-hr TWA Inhalation Exposures (AC, ADC and LADC) for Cold
Cleaner Based on Modeling
Category
Acute and Chr
Exposures (8-H<
AC 1-BP, 8-hr TWA a
50th Percentile
onic, Non-Cancer
)ur TWAs in ppm)
nd ADCl-BP, 8-hr TWA
95th Percentile
Chronic, Cancer
LADCi-
50th Percentile
Exposures (ppm)
BP, 8-hr TWA
95th Percentile
Confidence
Rating of Air
Concentration
Data
Worker
0.55
11.91
0.21
4.59
N/A-
Modeled Data
ONU
0.29
6.83
0.11
2.63
Strength, Limitation, and Uncertainty of the Inhalation Exposure Assessment
Exposure is assessed using 1-BP personal breathing zone monitoring data from OSHA CEHD, and the
data were determined to have a high confidence rating through EPA's systematic review process.
However, CEHD data are obtained from OSHA inspections and are not intended to represent typical
exposure levels at the workplace. In addition, monitoring data for a CSHO may not be representative of
the exposure level for the typical occupational non-users.
The exposure monitoring data is supplemented with near-field/far-field exposure modeling using a
Monte Carlo approach. The exposure model was peer reviewed as part of the 2016 Draft Risk
Assessment (U.S. EPA. 2016c). The model references EPA AP-42 emission factors for generic, non-
Page 104 of 486
-------
methane VOC. These emission factors may not be representative of emissions for 1-BP, and could result
in either an over- or underestimate. Despite these uncertainties, the model results are in good agreement
with the exposure monitoring data. Based on reasonably available information above, EPA has a high
level of confidence in the assessed exposure.
2.3.1.15 Aerosol Spray Degreaser/Cleaner
Process Descriptions
Aerosol degreasing is a process that uses an aerosolized solvent spray, typically applied from a
pressurized can, to remove residual contaminants from fabricated parts. Based on identified safety data
sheets (SDS), 1-BP-based formulations typically use carbon dioxide, liquified petroleum gas (LPG) {i.e.,
propane and butane), 1,1,1,2-tetrafluoroethane, 1,1-difluoroethane, and pentafluorobutane as the carrier
gas (U.S. EPA 2017c). The aerosol droplets bead up on the fabricated part and then drip off, carrying
away any contaminants and leaving behind a clean surface.
Figure 2-6 illustrates the typical process of using aerosol degreasing to clean components in commercial
settings. One example of a commercial setting with aerosol degreasing operations is repair shops, where
service items are cleaned to remove any contaminants that would otherwise compromise the service
item's operation. Internal components may be cleaned in place or removed from the service item,
cleaned, and then re-installed once dry (U.S. EPA 2014a). Example uses of aerosol products containing
1-BP include general purpose degreasing, engine degreasing, brake cleaning, and metal product cleaning
applications.
Figure 2-6. Overview of Aerosol degreasing
Assessment of Inhalation Exposure Based on Monitoring Data
Table 2-18 summarizes 8-hr TWA PBZ monitoring data for aerosol degreasing obtained from (Stewart.
1998) and (Tech Spray. 2003). The Stewart (1998) study measured 1-BP worker PBZ during an aerosol
spray can application on a test substrate consisting of a small electric motor; the scenario was intended
to simulate workers performing typical repair and maintenance work. The Tech Spray (2003) study
measured worker exposure in a test scenario that simulated cleaning of printed circuit boards for the
repair of computers and electrical systems. Among the two test studies, the 50th and 95th percentile
worker exposures were 16.1 ppm and 31.6 ppm, respectively.
The Tech Spray study tested an exposure scenario where the 1-BP aerosol degreasing occurred inside a
non-vented booth. Subsequently, the company tested the same scenario in a vented booth. With a non-
Page 105 of 486
-------
vented booth, worker exposure ranged from 13 to 32 ppm 8-hr TWA. With the vented booth, worker
exposure was reduced to 5.50 ppm 8-hr TWA based on a single data point. The representativeness of
this single data point as a post-EC scenario is unknown. The vented booth scenario has a constant draw
of 0.9 cubic meters per second during the 8-hour test. The data suggest the significance of ventilation
and its impact on worker exposure.
Table 2-18. Summary of 1-BP 8-hr TWA Exposures (AC, ADC and LADC) for Aerosol Spray
Degreaser/Cleaner Based on Monitoring Data
Categorya
Acute and Chron
Exposures (8-Hou
ACi bp, 8-hr twa and
50th Percentile
ic, Non-Cancer
r TWAs in ppm)
ADCl-BP, 8-hr TWA
95th Percentile
Chronic, Cane
(PP
LADCi-bi
50th Percentile
er Exposures
m)
P, 8-hr TWA
95th Percentile
Data
Points
Confidence
Rating of Air
Concentration
Data
Worker,
Pre EC
16.1
31.6
6.38
16.2
6
Medium
Worker,
Post EC b
5.50
2.19
2.82
1
Source: Stewart (1998): Tech Spray (2003). as cited in (U.S. EPA. 2006b). The vented booth scenario from Tech Spray is
used as the post-EC scenario, and the remaining data points are used as the pre-EC scenario.
a Worker includes operators, technicians, mechanics, and maintenance supervisor. Data are not available for occupational
non-users.
b The 8-hr TWA exposure estimate is combined with 50th and 95th percentile value on the number of working years to
calculate LADC. See Appendix B.
In addition to the data summarized above, the Tech Spray study included a test scenario that measured
short-term worker exposure that simulated an automotive repair shop. In this test, 1-BP was sprayed
continuously over a 15-minute period. In reality, workers are only expected to spray 1-BP for a few
minutes at a time; as such, the test was intended to simulate a heavy-usage scenario at this facility. The
15-min short term exposure for operators ranged from 190 to 1,100 ppm. Further, the 15-minute short
term exposure for a worker in an adjacent room measured 11 ppm ((Tech Spray, 2003). as cited in (U.S.
EPA, 2006b)). The presence of 1-BP in the adjacent room suggests the infiltration of contaminated air
into other work areas.
Assessment of Inhalation Exposure Based on Modeling
Aerosol degreasing formulations containing 1-BP can be used at a variety of workplaces. For the
purpose of modeling, EPA modeled worker exposure to 1-BP during brake servicing as a representative
exposure scenario. EPA chose to model this scenario because the process of brake servicing is well
understood and there is sufficient data to construct such a model. EPA believes brake servicing and
engine degreasing at automotive maintenance and repair shops is a common application for products
containing 1-BP, and the process is a representative aerosol degreasing scenario.
Figure 2-7 illustrates the Brake Servicing Near-Field Far-Field Inhalation Exposure Model. The general
model framework was previously included in the 2016 Draft Risk Assessment (U.S. EPA, 2016c);
however, specific model parameters have been updated with data from a recent CARB study. As the
figure shows, 1-BP in aerosolized droplets immediately volatilizes into the near-field, resulting in
worker exposures at a concentration Cnf. The concentration is directly proportional to the amount of
aerosol degreaser applied by the worker, who is standing in the near-field-zone (i.e., the working zone).
Page 106 of 486
-------
The volume of this zone is denoted by Vnf. The ventilation rate for the near-field zone (Qnf) determines
how quickly 1-BP dissipates into the far-field {i.e., the facility space surrounding the near-field),
resulting in occupational non-user exposures to 1-BP at a concentration Cff. Vff denotes the volume of
the far-field space into which the 1-BP dissipates out of the near-field. The ventilation rate for the
surroundings, denoted by Qff, determines how quickly 1-BP dissipates out of the surrounding space and
into the outside air.
In this scenario, 1-BP vapors enter the near-field in non-steady "bursts," where each burst results in a
sudden rise in the near-field concentration, followed by a more gradual rise in the far-field
concentration. The near-field and far-field concentrations then decay with time until the next burst
causes a new rise in near-field concentration. The product application rate is based on a 2000 CARB
report for brake servicing, which estimates that each facility performs on average 936 brake jobs per
year, and that each brake job requires approximately 14.4 ounces of product. For each model iteration,
EPA determined the concentration of 1-BP by assuming the formulation could be one of 25 possible
aerosol degreasing products identified in the Preliminary Information on Manufacturing, Processing,
Distribution, Use, and Disposal: 1-Bromopropane (U.S. EPA. 2017c). Detailed model parameters and
assumptions are presented in the Supplemental Information on Occupational Exposure Assessment
(EPA. 2019f). EPA did not model a "post-EC" scenario because there is not sufficient information to
determine the type and effectiveness of engineering control at automotive and other commercial
degreasing facilities.
NF C
v£
Volatile Source \%
Figure 2-7. Schematic of the Near-Field/Far-Field Model for Aerosol degreasing
EPA performed a Monte Carlo simulation with 100,000 iterations and the Latin hypercube sampling
method to model near-field and far-field exposure concentrations in the aerosol degreasing scenario.
Table 2-19 presents a statistical summary of the exposure modeling results. The 50th and 95th percentile
exposures are 6.37 ppm and 22.53 ppm 8-hr TWA for workers, and 0.11 ppm and 0.93 ppm 8-hr TWA
for occupational non-users.
Page 107 of 486
-------
Table 2-19. Summary of 1-BP 8-hr TWA Exposures (AC, ADC and LADC) for Aerosol Spray
Degreaser/Cleaner Based on Modeling
Category
Acute and Chr
Exposures (8-H<
AC 1-BP, 8-hr TWA a
50th Percentile
onic, Non-Cancer
)ur TWAs in ppm)
nd ADCl-BP, 8-hr TWA
95th Percentile
Chronic, Cancer
LADCi-
50th Percentile
Exposures (ppm)
BP, 8-hr TWA
95th Percentile
Confidence
Rating of Air
Concentration
Data
Worker
6.37
22.53
2.38
9.05
N/A-
Modeled Data
ONU
0.11
0.93
0.04
0.36
Strength, Limitation, and Uncertainty of the Inhalation Exposure Assessment
Exposure is assessed using 1-BP personal breathing zone monitoring data specific to aerosol degreasing.
The data come from two studies with "medium" confidence rating.
The exposure monitoring data are supplemented with the Brake Servicing Near-Field/Far-Field
Inhalation Exposure Model, which provides exposure estimates for a brake cleaning scenario. The
model uses a Monte Carlo approach to incorporate variability. Although the model scenario is specific
to brake cleaning and may not encompass the full range of aerosol degreasing scenarios, the model
results are in good agreement with monitoring data. Based on reasonably available information above,
EPA has a high level of confidence in the assessed exposure.
2.3.1.16 Dry Cleaning
Process Descriptions
1-BP is a solvent used in dry cleaning machines. There are two known 1-BP based dry cleaning
formulations, DrySolv® and Fabrisolv™ XL, which were introduced beginning in 2006. These
formulations are often marketed as "drop-in" replacements for perchloroethylene (PERC), which
indicates they can be used in third generation or higher Perc equipment (TURI. 2012). Third generation
equipment, introduced in the late 1970s and early 1980s, are non-vented, dry-to-dry machines with
refrigerated condensers. These machines are essentially closed systems and are only open to the
atmosphere when the machine door is opened. In third generation machines, heated drying air is
recirculated back to the drying drum through a vapor recovery system (CDC. 1997).
Fourth generation dry cleaning equipment are essentially third-generation machines with added
secondary vapor control. These machines "rely on both a refrigerated condenser and carbon adsorbent to
reduce the Perc concentration at the cylinder outlet below 300 ppm at the end of the dry cycle," and are
more effective at recovering solvent vapors (CDC. 1997). Fifth generation equipment have the same
features as fourth generation machines, but also have a monitor inside the machine drum and an
interlocking system to ensure that the concentration is below approximately 300 ppm before the loading
door can be opened (CDC. 1997).
Dry cleaners who opt to use 1-BP can either convert existing Perc machines or purchase a new dry
cleaning machine specifically designed for 1-BP. To convert existing Perc machines to use 1-BP,
machine settings and components must be changed to prevent machine overheating and solvent leaks
(Blando et al.. 2010). 1-BP is known to damage rubber gaskets and seals. It can also degrade cast
Page 108 of 486
-------
aluminum, which is sometimes used on equipment doors and other dry cleaning machine components. In
addition, 1-BP is not compatible with polyurethane and silicone (TURI, 2012). Enviro Tech
International, Inc. (Enviro Tech), a major 1-BP supplier, recently ceased selling DrySolv® to users of
converted Perc machines (Enviro Tech International. 2017).
Figure 2-8 provides an overview of the dry cleaning process. Worker exposure monitoring studies for 1-
BP at dry cleaning facilities suggest workers are exposed when 1) adding make-up solvent, typically by
manually dumping it through the front hatch, 2) opening the machine door during the wash cycle, and 3)
removing loads from the machines (Blando et al., 2010).
Engineering controls such as local exhaust ventilation (LEV) located at or near the machine door can
reduce worker exposure during machine loading, machine unloading, and maintenance activities
(NCDOL. 2013V
Receiving Garments
Pre-Spotting
Dry Cleaning
n
Finishing
Post-Spotting
Figure 2-8. Overview of Dry Cleaning
Assessment of Inhalation Exposure Based on Monitoring Data
Table 2-20 presents an analysis of the 8-hr TWA Personal Breathing Zone (PBZ) monitoring data from
literature. The data were obtained from two literature studies covering the same four dry cleaning shops
in New Jersey. The studies noted that work load and work practices varied greatly among the shops,
resulting in variability in 1-BP exposure across these shops. In addition, there was variability in 1-BP
exposure across different job titles, and in some cases on different days when the exposure monitoring
was conducted. One study (Eisenberg and Ramsey. 2010) contains additional partial-shift exposure data
that are not summarized here. For those data, an 8-hr TWA value was not obtained because owners of
the shop requested that NIOSH remove the sampling equipment once they had finished running the dry
cleaning machines (Eisenberg and Ramsey. 2010).
Page 109 of 486
-------
All four shops included in the studies used converted 3rd generation machines (Blando et al.. 2010). The
shops dry cleaned one to 14 loads of garments per day. Some shops that converted the machines
themselves "cooked" the solvent, a practice that had been performed widely for Perc but is no longer
recommended by the manufacturers for 1-BP operation (Eisenberg and Ramsey. 2010). Only one shop
added make-up solvent on Sample Day 1 and Sample Day 2 by manually dumping a 5-gallon can of
solvent product through the front hatch of the machine (Blando et al.. 2010). The facilities had general
building ventilation, ceiling-mounted or wall-mounted fans, but lacked controls specifically designed to
reduce exposure to the dry cleaning solvent.
EPA defined workers as employees who operate dry cleaning machine or who perform dry cleaning
activities such as spotting, pressing and finishing. For workers, the 50th and 95th percentile exposures are
29.4 ppm and 50.2 ppm 8-hr TWA, respectively. The exposure level is impacted by the number of loads
cleaned, the number of solvent "cooking" (heating the solvent for recovery) cycles used, and whether
any make-up solvent was added in that particular shop and on that particular day when the monitoring
was conducted (Blando et al.. 2010). The highest 1-BP concentration in air was found when a facility
with a converted Perc machine cooked the solvent (Eisenberg and Ramsey. 2010).
EPA defined occupational non-users as employees who work in the dry cleaning shops but do not
perform dry cleaning activities. For occupational non-users, the 50th and 95th percentile exposures are
12.1 ppm and 20.6 ppm 8-hr TWA, respectively. The data suggest that cashiers, clerks, and other
employees at the shop are also exposed to 1-BP. In addition to occupational non-users, children may
also be present at some small, family-owned dry cleaning shops, and thereby be exposed to 1-BP. The
monitoring studies do not contain information on exposure to children.
Table 2-20. Summary of 1-BP 8-hr TWA Exposures (AC, ADC and LADC) for Dry Cleaning
Based on Monitoring Data
Category
Acute and Chro
Exposures (8-Ho
AC 1-BP, 8-hr TWA ail
50th Percentile
nic, Non-Cancer
ur TWAs in ppm)
(1 ADC 1-BP, 8-hr TWA
95th Percentile
Chronic, Can
(IT
LADCi-b
50th Percentile
cer Exposures
m)
P, 8-hr TWA
95th Percentile
Data
Points
Confidence
Rating of Air
Concentration
Data
Workera
29.4
50.2
11.7
25.7
8
High
ONUb
12.1
20.6
4.80
10.6
6
Source: (Blando et al.. 2010: Eisenberg and Ramsey. 2010: NIOSH. 2010)
a Worker refers to dry cleaning machine operators.
b Occupational non-user refers to cashiers and clerks.
Assessment of Inhalation Exposure Based on Modeling
Because there are multiple activities with potential 1-BP exposure at a dry cleaner, a multi-zone
modeling approach is used to account for 1-BP vapor generation from multiple sources. Figure 2-9
illustrates this multi-zone approach, which considers the following three worker activities:
• Spot cleaning of stains on both dirty and clean garments: On receiving a garment, dry cleaners
inspect for stains or spots they can remove as much of as possible before cleaning the garment in a
dry cleaning machine. Spot cleaning may also occur after dry cleaning if the stains or spots were not
adequately removed. Spot cleaning occurs on a spotting board and can involve the use of a spotting
Page 110 of 486
-------
agent containing various solvents, such as 1-BP. Workers are exposed to 1-BP when applying it via
squeeze bottles, hand-held spray bottles, or even from spray guns connected to pressurized tanks.
Once applied, the worker may come into further contact with the 1-BP if using a brush, spatula,
pressurized air or steam, or their fingers to scrape or flush away the stain (Young. 2012; NIOSH.
1997). For modeling, EPA assumed the near-field is a rectangular volume covering the body of a
worker.
• Unloading garments from dry cleaning machines: At the end of each dry cleaning cycle, workers
manually open the machine door to retrieve cleaned garments. During this activity, workers are
exposed to 1-BP vapors remaining in the dry cleaning machine cylinder. For modeling, EPA
assumed that the near-field consists of a hemispherical area surrounding the machine door, and that
the entire cylinder volume of air containing 1-BP exchanges with the workplace air, resulting in a
"spike" in 1-BP concentration in the near-field, Cd, during each unloading event. This concentration
is directly proportional to the amount of residual 1-BP in the cylinder when the door is opened. The
near-field concentration then decays with time until the next unloading event occurs.
• Finishing and pressing: The cleaned garments taken out of the cylinder after each dry clean cycle
contain residual solvents and are not completely dried (Von Grote et al.. 2003). The residual solvents
are continuously emitted into the workplace during pressing and finishing, where workers manually
place the cleaned garments on the pressing machine to be steamed and ironed. EPA assumed any
residual solvent is entirely evaporated during pressing, resulting in an increase in the near-field 1-BP
concentration during this activity. Workers are exposed to 1-BP vapors while standing in vicinity of
the press machine. For modeling, EPA assumed the near-field is a rectangular volume covering the
body of a worker.
Page 111 of486
-------
Dry Cleaning
Machine
Far-field (background)
Figure 2-9. Illustration of the Multi-Zone Model
As the figure shows, 1-BP vapor is generated in each of the three near-fields, resulting in worker
exposures at concentrations Cs, Cd, and Cf. The volume of each zone is denoted by Vs, Vd, and Vf. The
ventilation rate for the near-field zone (Qs, Qd, Qf) determines how quickly 1-BP dissipates into the far-
field {i.e., the facility space surrounding the near-fields), resulting in occupational non-user exposures to
1-BP at a concentration Cff. Vff denotes the volume of the far-field space into which the 1-BP
dissipates out of the near-field. The ventilation rate for the surroundings, denoted by Qff, determines
how quickly 1-BP dissipates out of the surrounding space and into the outside air. The Supplemental
Information on Occupational Exposure Assessment (EPA. 2019f) summarizes the parameters and
equations for the multi-zone model. The far-field volume, air exchange rate, and near-field indoor wind
speed are identical to those used in the 1-BP Spot Cleaning Model (see Section 2.3.1.17). These values
were selected using engineering judgment and literature data that EPA believed to be representative of a
typical dry cleaner.
Based on recent communication with Enviro Tech, only eight dry cleaning establishments were using 1-
BP in 2019 (Enviro Tech International 2019). EPA assumed these eight dry cleaning shops are small
shops that operate up to 12 hours a day and up to 6 days a week. In addition, EPA assumed each shop
only has a single machine. The assumption is supported by an industry study conducted in King County,
Washington, where 96 percent of 151 respondents reported having only one machine at their facility.
Four reported having two machines, and two reported having three machines (Whittaker and Johanson.
2011).
EPA modeled the baseline scenario assuming the facility operates a converted third generation machine,
the machine type observed at all three New Jersey dry cleaners in the Blando et al. (2010) study. For the
Page 112 of 486
-------
engineering control scenario, EPA modeled a facility with a fourth generation machine. EPA believes
facilities using 1-BP are unlikely to own fifth generation machines (ERG. 2005).
EPA assessed three types of workers within the modeled dry cleaning facility: 1) a worker who performs
spot cleaning; 2) a worker who unloads the dry cleaning machine and finishes and presses the garments;
and 3) an occupational non-user. Each worker type is described in further detail below. EPA assumed
each worker activity is performed over the full 12-hour operating day.
• EPA assumed spot cleaning occurs for a duration varying from two to five hours in the middle of the
twelve-hour day. The worker is exposed at the spot cleaning near-field concentration during this
time, and at the far-field concentration for the remainder of the day. Spot cleaning can be performed
for both dry cleaned loads and for laundered loads.
• EPA assumed a separate worker unloads the dry cleaning machine, and finishes and presses the
garments. After each load, EPA assumed this worker spends five minutes unloading the machine,
during which he or she is exposed at the machine near-field concentration. After unloading, the
worker spends five minutes in the finishing near-field to prepare the garments. Then, the worker
spends another 20 minutes finishing and pressing the cleaned garments. During this 20-minute
period of finishing and pressing, the residual 1-BP solvent is off-gassed into the finishing near-field.
The amount of residual 1-BP solvent is estimated using measured data presented in (VonGroteet
al.. 2003). These unloading and finishing activities are assumed to occur at regular intervals
throughout the twelve-hour day. The frequency of unloading and finishing depends on the number of
loads dry cleaned each day, which varies from one to 14, where 14 was the maximum number of
loads observed in the studies (Blando et al.. 2010; Eisenberg and Ramsey. 2010). When this worker
is not unloading the dry cleaning machine or finishing and pressing garments, the worker is exposed
at the far-field concentration.
• EPA assumed one occupational non-user is exposed at the far-field concentration for twelve hours a
day. The occupational non-user could be the cashier, tailor, or launderer, who works at the facility
but does not perform dry cleaning activities.
Table 2-21 presents the Monte Carlo results with the Latin hypercube sampling method and 10,000
iterations. Statistics of the 12-hr TWA exposures24 (95th and 50th percentiles) are calculated at the end of
the simulation after all iterations have completed. The AC, ADC, and LADC calculations are integrated
into the Monte Carlo simulation, such that the exposure frequency matches the model input values for
each iteration. As shown in the table, the worker who performs unloading and finishing activities have
the highest exposure; this exposure can be reduced if the facility switches from a third generation to a
fourth generation machine. However, the machine type does not significantly impact exposure level for
other persons present at the facility, including the spot cleaner and the occupational non-user. The model
values cover a wider distribution of exposure levels when compared to the monitoring data. This is
likely due to the wide range of model input parameter values covering a higher number of possible
exposure scenarios. However, the modeled occupational non-user exposures are lower than actual
24 The 12-hr TWA values are the model exposure concentration averaged over a 12-hr period. These values do not follow the
OSHA extended shift policy.
Page 113 of 486
-------
monitoring results. The model assumes the occupational non-user spends their time entirely in the far-
field. In reality, these employees may occasionally perform activities in the near-field, thereby having a
higher level of exposure.
Table 2-22 presents the exposure concentration for children who may be present at the dry cleaning
facility. Because many dry cleaners are family owned and operated, it is possible that children may be
present for a four-hour period (3 - 7pm) after school, during which they may be exposed at similar
levels as occupational non-users. The table provides the 4-hr TWA exposure concentration and the 24-hr
TWA AC. EPA could not calculate exposure for chronic scenarios (ADC and LADC) due to uncertainty
in the exposure frequency and number of years with exposure for children. EPA believes these
exposures are unlikely to be chronic in nature.25 In addition, it is unclear whether children are present at
any of the remaining eight dry cleaners.
Table 2-21. Summary of 1-BP Dry Cleaning Exposures for Workers and Occupational Non-users
Based on Modeling
Machine Type
12-hr TWA
(PP
Ci-bp, i:
50th
Percentile
Exposures
m)
.-hr TWA
95th
Percentile
Acute, No
Exposur
AC l-BP,
50th
Percentile
n-Cancer
es (ppm)
24-hr TWA
95th
Percentile
Chronic, P
Exposui
ADCibi
50th
Percentile
Jon-Cancer
•es (ppm)
>, 24-hr TWA
95th
Percentile
Chronic
Exposur
LADCib
50th
Percentile
, Cancer
es (ppm)
P, 24-hr TWA
95th
Percentile
Workers: Machine Unloading and Finishing (Near-Field)
3 rd Gen.
14.1
60.5
7.06
30.3
4.98
21.70
1.89
8.57
4th Gen.
2.38
6.36
1.19
3.18
0.84
2.30
0.31
0.94
Workers: Spot Cleaning (Near-Field)
3rd Gen.
2.93
7.93
1.47
3.97
1.03
2.83
0.39
1.14
4th Gen.
2.40
5.65
1.20
2.83
0.85
2.02
0.32
0.82
Occupational non-users (Far-Field)
3rd Gen.
1.82
6.65
0.91
3.33
0.64
2.37
0.24
0.95
4th Gen.
1.31
4.21
0.65
2.11
0.46
1.49
0.17
0.60
Confidence rating of air concentration data: N/A - modeled data.
Table 2-22. Summary of 1-BP Dry Cleaning Exposures for Children Based on Modeling
Machine Type
4-hr TWA
(PP
C 1-BP, 4
50th
Percentile
Exposures
m)
-hr TWA
95th
Percentile
Acute, No
Exposur
ACi-bp,
50th
Percentile
n-Cancer
es (ppm)
24-hr TWA
95th
Percentile
Chronic, Is
Exposur
ADCibi
50th
Percentile
Jon-Cancer
es (ppm)
>, 24-hr TWA
95th
Percentile
Chronic
Exposur
LADCib
50th
Percentile
, Cancer
es (ppm)
P, 24-hr TWA
95th
Percentile
Children (Far-Field)
3 rd Gen.
0.54
4.03
0.09
0.67
N/A
N/A
N/A
N/A
4th Gen.
0.09
1.02
0.01
0.17
N/A
N/A
N/A
N/A
25 EPA did not calculate risk for children associated with acute exposure at dry cleaners because the acute health domains
(developmental effects) are not applicable to children. Further, EPA did not calculate risks for chronic and cancer scenarios
for children at dry cleaners because EPA believes exposure to children at workplaces are unlikely to be chronic in nature.
Page 114 of 486
-------
N/A - Not applicable
Confidence rating of air concentration data: N/A - modeled data.
Strength, Limitation, and Uncertainty of the Inhalation Exposure Assessment
For this condition of use, exposure is assessed using 1-BP personal breathing zone monitoring data from
three different studies, all of which have a high confidence rating as determined through EPA's
systematic review process. The monitoring data, which were collected from facilities using converted
third generation machines, are in good agreement with model results for the same machine type.
The multi-zone Dry Cleaning model (peer reviewed in 2016) uses a Monte Carlo approach to
incorporate variability in the environmental conditions, worker activity patterns, use rate, and other
model input parameters. The model assumes each dry cleaner operates a single machine, and does not
represent exposures for larger facilities that may have multiple machines. Based on reasonably available
information above, EPA has a high level of confidence in the assessed exposure for these machine types.
2.3.1.17 Spot Cleaner, Stain Remover
Process Descriptions
EPA assessed a separate spot cleaning scenario at dry cleaners. This scenario represents dry cleaners or
other shops that use 1-BP-based spot cleaning formulations but do not otherwise use 1-BP in a dry
cleaning machine. The extent of such uses is likely limited, as Enviro Tech claimed that while DrySolv
spotting products were advertised to the dry cleaning industry, most were never commercialized (Enviro
Tech International. 2017).
On receiving a garment, dry cleaners inspect for stains or spots and remove as much of them as possible
before cleaning the garment in a machine. As Figure 2-10 shows, spot cleaning occurs on a spotting
board and can involve the use of a spotting agent containing various solvents, such as 1-BP. The
spotting agent can be applied from squeeze bottles, hand-held spray bottles, or even from spray guns
connected to pressurized tanks. Once applied, the dry cleaner may come into further contact with the 1-
BP if using a brush, spatula, pressurized air or steam, or their fingers to scrape or flush away the stain
(Young. 2012; NIOSH. 1997).
Figure 2-10. Overview of Use of Spot Cleaning at Dry Cleaners
Assessment of Inhalation Exposure Based on Monitoring Data
Table 2-23 presents 8-hr TWA PBZ monitoring data from OSHA CEHD for three facilities where spot
cleaning is performed. At one facility, workers spray-applied solvent formulation to stained portions of
dresses and did not wear any personal protective equipment. It is unclear if there were any engineering
controls at the facility to mitigate worker exposure.
Page 115 of 486
-------
The 50th and 95th percentile exposure level for workers were 0.90 ppm and 4.73 ppm 8-hr TWA,
respectively. No exposure monitoring data are available for occupational non-users.
Table 2-23. Summary of 1-BP 8-hr TWA Exposures (AC, ADC and LADC) for Spot Cleaner
Based on Monitoring Data
Category
Acute and Chron
Exposures (8-Hou
ACi bp, 8-hr twa and
50th Percentile
ic, Non-Cancer
r TWAs in ppm)
ADCl-BP, 8-hr TWA
95th Percentile
Chronic, Cane
(PP
LADCi-bi
50th Percentile
er Exposures
m)
P, 8-hr TWA
95th Percentile
Data
Points
Confidence
Rating of Air
Concentration
Data
Worker
0.90
4.73
0.36
2.42
6
High
Source: (OSHA. 2019. 2013b)
Assessment of Inhalation Exposure Based on Modeling
Figure 2-11 illustrates the near-field/far-field modeling approach that EPA applied to spot cleaning
facilities. The model, including all input parameters, are described in more detail in the Supplemental
Information on Occupational Exposure Assessment (EPA. 2019f).
As the figure shows, chemical vapors evaporate into the near-field (at evaporation rate G), resulting in
near-field exposures to workers at a concentration Cnf. The concentration is directly proportional to the
amount of spot cleaner applied by the worker, who is standing in the near-field-zone (i.e., the working
zone). The volume of this zone is denoted by Vnf. The ventilation rate for the near-field zone (Qnf)
determines how quickly the chemical of interest dissipates into the far-field (i.e., the facility space
surrounding the near-field), resulting in occupational non-user exposures at a concentration Cff. Vff
denotes the volume of the far-field space into which the chemical of interest dissipates out of the near-
field. The ventilation rate for the surroundings, denoted by Qff, determines how quickly the chemical
dissipates out of the surrounding space and into the outdoor air.
Far-Field
Volatile Source
Page 116 of 486
-------
Figure 2-11. Schematic of the Near-Field/Far-Field Model for Spot Cleaning
To determine the 1-BP use rate, EPA references a comparative analysis from the Massachusetts
Department of Environmental Protection (MassDEP), which contains case studies of Perc alternatives
that can be potentially used at dry cleaners. One case study estimates a dry cleaner spends $60 per
month on spotting agents containing 1-BP. This particular facility dry cleans 100 pieces of garments per
day. MassDEP noted that the facility size can vary greatly among individual dry cleaners (MassDEP.
2013). Blando et al. (2009) estimated that 1-BP solvent products cost $45 per gallon. Based on this
information, EPA calculated a spot cleaner use rate of 1.33 gallons per month, or 16 gallons per year.
The Safety Data Sheet for DrySolv, a common 1-BP formulation, indicates the product contains greater
than 87 percent 1-BP by weight (Enviro Tech International. 2013).
EPA performed Monte Carlo simulations, applying 100,000 iterations and the Latin hypercube sampling
method. Table 2-24 presents a statistical summary of the exposure modeling results. The 50th and 95th
percentile exposure for workers (near-field) are 3.24 ppm and 7.03 ppm 8-hr TWA, respectively. These
results are generally comparable to the monitoring data. For occupational non-users (far-field), the 50th
and 95th percentile exposure levels are 1.63 ppm and 4.68 ppm 8-hr TWA, respectively. The table also
presents the AC, ADC, and LADC values, which are integrated into the Monte Carlo. EPA assumes no
engineering controls (e.g., exhaust hoods) are present at spot cleaning facilities, because controls may
not be financially feasible for small shops.
Table 2-24. Summary of 1-BP 8-hr TWA Exposures (AC, ADC and LADC) for Use of Spot
Cleaner Based on Modeling
Category
Acute, ]>
Exposures I
in
ACi-b
50th
Percentile
on-Cancer
8-Hour TWAs
ppm)
P, 8-hr TWA
95th
Percentile
Chronic, N
Exposures (8-
inpi
ADC l-BP
50th
Percentile
on-Cancer
Hour TWAs
)m)
8-hr TWA
95th
Percentile
Chronic
Exposur
LADCi-b
50th
Percentile
Cancer
es (ppm)
P, 8-hr TWA
95th
Percentile
Confidence
Rating of Air
Concentration
Data
Worker
3.24
7.03
0.76
1.66
0.29
0.68
N/A-
Modeled Data
ONU
1.63
4.68
0.38
1.10
0.15
0.45
Strength, Limitation, and Uncertainty of the Inhalation Exposure Assessment
For this condition of use, the 1-BP personal breathing zone monitoring data have a high confidence
rating as determined through EPA's systematic review process. The data, however, come from OSHA
CEHD, which is not intended to represent typical workplace exposure levels.
The monitoring data are supplemented with the near-field/far-field Spot Cleaning exposure model. The
model incorporates a Monte Carlo simulation to address variability, and the model has been previously
peer reviewed in 2016. Although there is uncertainty in the representativeness of the spot cleaner use
rate from the MassDEP case study used in modeling, the model results are in good agreement with the
monitoring data. Based on reasonably available information above, EPA has a high level of confidence
in the assessed exposure.
Page 117 of 486
-------
2.3.1.18 Adhesive Chemicals (Spray Adhesives)
Process Descriptions
1-BP is used in spray adhesives for foam cushion manufacturing and fabrication (e.g., the furniture
industry). Figure 2-12 illustrates a typical process of using spray adhesives. During foam cushion
manufacturing and fabrication, foam is cut into pieces and then bonded together to achieve the
appropriate shape. Spray guns are used to spray-apply an adhesive onto flexible foam surfaces for
bonding. Adhesive spraying typically occurs either on an open top workbench with side panels that may
have some local ventilation, or in an open workspace with general room ventilation. After the adhesive
is applied, workers assemble the cushions by hand-pressing together pieces of cut flexible foam
(NIOSH. 2003b. 2002b).
Spray adhesive
Align and compress foam
Finished furniture products
Fabricate furniture
Figure 2-12. Overview of Use of Spray Adhesive in the Furniture Industry
Assessment of Inhalation Exposure Based on Monitoring Data
1-BP exposure monitoring data were identified in several sources, including journal articles, NIOSH
HHEs, and OSHA CEHD database. NIOSH HHEs are conducted at the request of employees,
employers, or union officials and help inform on potential hazards present at the workplace. HHEs can
also be conducted in response to a technical assistance request from other government agencies. OSHA
CEHD are workplace monitoring data from OSHA inspections. These inspections can be random or
targeted, or can be the result of a worker complaint.
Page 118 of 486
-------
Among these sources, three NIOSH studies provide the most comprehensive information on worker
exposure to 1-BP from spray adhesives in foam cushion manufacturing. Two of the three HHEs also
compare exposure pre- and post-engineering controls (EC). A summary of these HHEs follows:
• From March 1998 to April 2001, NIOSH investigated a facility in Mooresville, North Carolina to
assess 1-BP exposures during manufacturing of foam seat cushions (Reh et al.. 2002). The company
had four departments: Saw, Assembly, Sew, and Covers. Workers in Assembly and Covers
departments worked directly with the adhesive; however, workers in all four departments were
exposed. The spray adhesive used at this facility contained between 60 and 80 percent 1-BP. NIOSH
conducted an initial exposure assessment in 1998 and observed that the ventilation exhaust filters
were clogged with adhesive. In 2001, NIOSH conducted a follow-up exposure assessment after the
facility made improvements to its ventilation system.
• From November 2000 to August 2001, NIOSH investigated workplace exposures to 1-BP during
manufacturing of foam seat cushions at another cushion company in North Carolina (NIOSH.
2002b). This facility used a spray adhesive containing 55 percent 1-BP. NIOSH conducted an initial
exposure assessment in 2000, and recommended that the facility reduce worker exposure by
enclosing the spray stations to create "spray booths." Subsequently, in 2001, NIOSH conducted a
follow-up assessment after spray station enclosures were installed.
• From April 1999 to May 2001, NIOSH investigated another cushion company in North Carolina
(NIOSH. 2003b). In this study, NIOSH conducted two separate exposure assessments. In the initial
assessment, NIOSH measured 1-BP inhalation exposures to workers in and near the adhesive spray
operation areas. In the second assessment, NIOSH measured additional 1-BP inhalation exposures at
the facility. There were no changes to the facility's local exhaust ventilation system between the first
and second assessment.
Table 2-25 summarizes available 1-BP exposure data from the NIOSH and OSHA sources. The data set
includes exposures in pre-EC and post-EC scenarios for each worker job category. EPA defined three
job categories for 1-BP spray adhesive use:
• Sprayers: Workers who perform manual spraying of 1-BP adhesive as a regular part of his or her
job;
• Non-spravers: Workers who are not "sprayers," but either handle the 1-BP adhesive or spend the
majority of their shift working in an area where spraying occurs. For example, the NIOSH (2002)
study indicated spraying occurs in the Assembly and Covers departments. EPA assumes workers in
these departments who do not perform spraying still work in the vicinity of spraying operations and
may be regularly exposed to 1-BP; and
• Occupational non-users: Workers who do not regularly perform work in an area of the facility where
spraying occurs. For example, EPA assumes workers in the Saw and Sew departments of the 2002
NIOSH study (2002) are "occupational non-users."
Page 119 of 486
-------
For each worker job category (sprayer, non-sprayer or occupational non-user) and exposure scenario
(pre-EC or post-EC), EPA calculated the 50111 and 95th percentile exposure levels from the observed data
set. Pre-EC exposure scenarios suggest that all workers at foam cushion manufacturing facilities that use
1-BP spray adhesives have substantial exposure to 1-BP. Sprayers have the highest levels of exposure
because they work directly with the 1-BP adhesive. However, non-sprayers and occupational non-users
may also be exposed.
In general, exposure levels for job categories vary widely depending on the worker's specific work
activity pattern, individual facility configuration, and proximity to the 1-BP adhesive. For example,
workers in the Saw and Sew departments in the NIOSH (2002) study classified as "occupational non-
users" are exposed at levels above 100 ppm 8-hr TWA. The high exposure levels are caused by their
proximity to spraying operations in other departments, even though no adhesive is used in the Saw and
Sew departments (Reh et al.. 2002). Additionally, some workers may not have a single assigned role; as
such, their exposure level will vary depending on the specific tasks performed.
Post-EC exposure scenarios suggest that engineering controls such as ventilation and spray booth
enclosure, if well designed, maintained, and operated, can reduce worker exposures by an order of
magnitude. However, engineering controls alone do not reduce exposures for sprayers and non-sprayers
to levels below 0.1 ppm, the time-weighted average threshold limit value (TLV) recommended by the
American Conference of Governmental Industrial Hygienists (ACGIH).
Additional 1-BP worker exposure monitoring data have been identified in other literature studies such as
Hanley et al. (2009; 2006b). Ichihara et al. (2002). and Majersik et al. (2007). However, these studies are
not used in EPA's analysis because they either do not provide individual data points or lack specific
information on worker job descriptions to adequately categorize the exposure results.
Page 120 of 486
-------
Table 2-25. Summary of 1-BP 8-hr TWA Exposures (AC, ADC and LADC) for Spray Adhesive on
Monitoring Data
('alcuniA
Aculc iind (
C;inccr l.xpos
T\\ As i
A('i ni\s in iw \
in-1
Mil
1 Vive ill ile
ironic. \on-
u its (S-11 on r
n ppm)
ind AIM i lii.s
»\
lJ5lli
IVivciililc
Chronic. Ciin
l
I.AIM i i
55lh
IVivenlile
Dala
l\l|llls
( niilideiice
kaliim of \ir
( oiiceiiiralioii
Dala
Sprayer, Pre EC
132.8
253.6
52.8
130.04
83
High
Sprayer, Post EC
17.8
41.9
7.08
21.5
49
Non-Sprayer b, Pre EC
127.2
210.9
50.6
108.1
31
Non-Sprayer b, Post EC
18.0
28.8
7.15
14.8
9
ONU°, Pre EC
3.0
128.7
1.19
66.0
39
ONU°, Post EC
2.0
5.48
0.79
2.81
17
Sources: (OSHA. 2013b: NIOSH. 2003b. 2002b: Reh et al.. 20021
aEC = Engineering Controls. Pre-EC = Initial NIOSH visit; Post EC = Follow-up NIOSH visit engineering controls
implemented: Enclosing spray tables to create "spray booths" and/or improve ventilation.
b Non-Sprayer refers to those employees who are not sprayers, but either handle the adhesive or spend the majority of their
shift working in an area where spraying occurs.
0 Occupational non-user refers to those employees who do not regularly work in a department/area where spraying occurs
(e.g., employees in saw and sew departments).
Strength, Limitation, and Uncertainty of the Inhalation Exposure Assessment
This condition of use assesses exposure using 1-BP personal breathing zone monitoring data from
several studies. All data have a high confidence rating as determined through EPA's systematic review
process. The individual data points in these studies are further characterized into either pre- or post-EC
scenarios, based on reasonably available information on engineering control. EPA has a high level of
confidence in the assessed exposure based on the confidence rating of the underlying monitoring data.
2.3.1.19 THERMAX™ Installation
Process Descriptions
1-BP is used in the production of a polyisocyanurate rigid board insulation produced by Dow Chemical
Company that goes by the trade name THERMAX™. THERMAX™ can be used for interior and
exterior applications including walls, ceilings, roofs, foundations, basements, and crawl spaces in
commercial and residential buildings. After THERMAX™ is installed, seams are typically covered with
aluminum foil tape. Additional wallboard, baseboard, or molding may then be installed over the
insulation26.
26 https://www.dupont.com/content/dam/dupont/amer/us/en/performance-building-solutions/public/documents/179-04453.pdf
Page 121 of 486
-------
Assessment of Inhalation Exposure Based on Modeling
EPA has not identified exposure monitoring data associated with this condition of use. THERMAX™
products comprise a polyisocyanurate foam core with aluminum facers on each side. Because the
aluminum facers inhibit the off-gassing of 1-BP, workers are only potentially exposed to 1-BP off-
gassed from edges of the insulation.
EPA conducted a screening-level analysis using EPA's Indoor Environment Concentrations in Buildings
with Conditioned and Unconditioned Zones (IECCU) model to estimate the potential 1-BP
concentration from off-gassing of THERMAX™ insulation. The IECCU model is a simulation program
that can be used to model indoor chemical air concentrations in buildings with multiple zones and
multiple sources and sinks. The IECCU model uses a general mass balance equation for a chemical of
interest to calculate the time series of indoor concentrations. The equation combines all processes
governing source emissions, convective transfer by bulk air, sorption, and re-emission by indoor sinks,
interactions with airborne particles and settled dust and gas-phase chemical reactions. Results of the
analysis show that worker and ONU exposure to 1-BP during installation would be below 0.01 ppm 8-hr
TWA inside a residential home for the initial work day, and less on subsequent days after install.
Additional details of this screening-level analysis can be found in Appendix L of 1-BP Supplemental
File: Supplemental Information on Occupational Exposure Assessment (EPA. 2019f).
2.3.1.20 Other Uses
Process Descriptions
Based on products identified in EPA's data gathering and information received in public comments, a
variety of other aerosol and non-aerosol uses may exist for 1-BP [see Preliminary Information on
Manufacturing, Processing, Distribution, Use, and Disposal: 1-Bromopropane, EPA-HQ-QPPT-2016-
0741-0003 (U.S. EPA. 2017cYl. Examples of these uses include, but are not limited to (AIA. 2017; CRC
Industries Inc.. 2017; Enviro Tech International. 2017; OSHA; NIOSH. 2013):
• Aerosol mold cleaning and release: 1-BP is a carrier solvent in aerosol mold cleaning and release
products. These products are used to coat the molds for injection molding, compression molding,
blow molding and extrusion applications. The product use rate varies depending on mold size and
frequency of re-application. This use is likely limited because 1-BP is not compatible with some
mold release applications.
• Asphalt extraction: 1-BP is used for asphalt extraction in centrifuge extractors, vacuum extractors,
and reflux extractors. In this process, 1-BP is used to separate asphalt from the aggregate and filler
material to allow for determination of asphalt content. This condition of use is expected to make up
one percent of the total domestic 1-BP use volume.
• Coin and scissor cleaner: 1-BP is used in product formulations designed to clean collectible coins
and scissors.
• General purpose degreaser: General purpose degreasing products containing 1-BP (both aerosol and
non-aerosol) are used in industrial settings, with usage varying widely by facility. Refineries and
utilities are known to be the largest volume users, with usage being cyclical as 1-BP is used to clean
Page 122 of 486
-------
and maintain equipment primarily during plant shutdowns. 1-BP is also used for heavy duty
transportation maintenance, e.g., maintaining buses, trains, trucks, etc.
• High voltage cable cleaner: 1-BP is contained in both aerosol and non-aerosol cleaning products,
which are used to clean the semi-conductive cores of high voltage cables when splicing and
terminating cables. A few ounces of product are used to clean each splice.
• Refrigerant flush: 1-BP is used to flush oxygen lines in hospitals and in the aerospace industry. 1-BP
is also used to clean refrigeration lines in various industries. This condition of use is expected to
make up one percent of the total domestic 1-BP use volume.
• Temperature indicator: 1-BP is used in temperature indicating fluids and coatings. These coatings
can be applied to fabrics, rubber, plastics, glass, and/or polished metal. When the substrate is heated,
the coating will melt at the designated temperature, leaving a mark on the surface. This condition of
use is expected to make up less than 0.5 percent of the total domestic 1-BP use volume.
• Other uses: 1-BP has a number of other uses, such as adhesive accelerant, as coating component for
pipes and fixtures, and as laboratory chemical for research and development.
Assessment of Inhalation Exposure Based on Monitoring Data
EPA has not identified exposure data associated with these conditions of use. The worker activity, use
pattern, and associated exposure will vary for each condition of use. For conditions of use where 1-BP is
used in an aerosol application, the exposure levels may be as high as those presented in Section 2.3.1.15.
Actual exposure levels for each condition of use will likely vary depending on the use volume,
engineering control, and PPE.
2.3.1.21 Disposal, Recycling
Process Descriptions
Each of the conditions of use of 1-BP may generate waste streams that are collected and transported to
third-party sites for disposal, treatment, or recycling. Industrial sites that treat or dispose onsite wastes
that they themselves generate are assessed in each condition of use assessment in Sections 2.3.1.5
through 2.3.1.20. Wastes containing 1-BP that are generated during a condition of use and sent to a
third-party site for treatment, disposal, or recycling may include wastewater, solid wastes, and other
wastes.
Solid wastes are defined under RCRA as any material that is discarded by being: abandoned; inherently
waste-like; a discarded military munition; or recycled in certain ways (certain instances of the generation
and legitimate reclamation of secondary materials are exempted as solid wastes under RCRA). Solid
wastes may subsequently meet RCRA's definition of hazardous waste by either being listed as a waste at
40 CFR §§ 261.30 to 261.35 or by meeting waste-like characteristics as defined at 40 CFR §§ 261.20 to
261.24. Solid wastes that are hazardous wastes are regulated under the more stringent requirements of
Subtitle C of RCRA, whereas non-hazardous solid wastes are regulated under the less stringent
requirements of Subtitle D of RCRA. Solid wastes containing 1-BP may be regulated as a hazardous
waste under RCRA waste code D001 for ignitable liquids (40 CFR 261.21). 1-BP may also be co-
mingled with solvent mixtures that are RCRA regulated substances. These wastes would be either
Page 123 of 486
-------
incinerated in a hazardous waste incinerator or disposed to a hazardous waste landfill. Some amount of
1-BP may be improperly disposed as municipal wastes, although they are likely to be a small fraction of
the overall waste stream. As stated in the Problem Formulation, releases to RCRA Subtitle C and
Subtitle D landfills are not included in this risk evaluation.
Assessment of Inhalation Exposure Based on Modeling
EPA did not identify exposure monitoring data related to waste treatment and disposal sites. To assess
worker exposure, EPA assumed wastes containing 1-BP are transported and handled as bulk liquid
shipments and modeled exposure using the Tank Truck andRailcar Loading and Unloading Release and
Inhalation Exposure Model (previously described in Section 2.3.1.6).
Table 2-26 summarizes the model exposures from waste handling activities. The model assumes liquid
wastes may contain a range of concentrations for 1-BP. The central tendency scenario assumes a mixture
containing 30 percent 1-BP, while the high-end scenario assumes the waste contains 100 percent 1-BP.
EPA does not know the typical 1-BP concentration in the waste stream and the model may not be
representative of the full distribution of possible exposure levels at waste disposal facilities.
Table 2-26. Summary of 1-BP 8-hr TWA Exposures (AC, ADC and LADC) for Disposal Based on
Modeling
Category
Acute and Chrc
Exposures (8-Ho
AC 1-BP, 8-hr TWA aU
Central tendency
>nic, Non-Cancer
ur TWAs in ppm)
id ADCl-BP, 8-hr TWA
High-end
Chronic, Cancer
LADCib
Central tendency
Exposures (ppm)
P, 8-hr TWA
High-end
Confidence
Rating of Air
Concentration
Data
Worker
3.83E-3
5.67E-2
1.52E-3
2.91E-2
N/A - Modeled
Data
Strength, Limitation, and Uncertainty of the Inhalation Exposure Assessment
The Tank Truck and Railcar Loading and Unloading Release and Inhalation Exposure Model is used to
estimate exposure. The model uses a combination of published EPA emission factors and engineering
judgement to estimate central tendency and high-end exposures. EPA believes the model exposures are
likely to be representative of exposure associated with bulk container loading. However, the model does
not account for other potential sources of exposure at industrial facilities, such as sampling, equipment
cleaning, and other process activities. The model also assumes only one container is loaded per day,
although larger facilities may have higher product loading frequencies. These model uncertainties could
result in an underestimate of the worker exposure.
Based on reasonably available information above, EPA has a medium level of confidence in the assessed
exposure.
2.3.1.22 Summary of Inhalation Exposure Assessment
Table 2-27 summarizes the inhalation exposure estimates for all occupational exposure scenarios. Where
statistics can be calculated, the central tendency estimate represents the 50th percentile exposure level of
the available data set, and the high-end estimate represents the 95th percentile exposure level. For most
conditions of use, the central tendency and high-end TWA exposures for both workers and ONUs are
Page 124 of 486
-------
above the ACGIH TLV of 0.1 ppm. The TWA exposures are 8-hr TWA, except for the dry cleaning
condition of use, where exposures are modeled as 12-hr TWA.
For conditions of use where both monitoring and model data are available, the results were found to be
in good agreement with each other (with difference less than one order of magnitude).
Page 125 of 486
-------
Table 2-27. Summary of Occupational Inhalation Exposure Results
Condition of Use
Exposure
Scenario
Category
TWA Exposures
Chronic, Cancer Exposures
Statistical Value for
Central Tendency
and High-end
Data Type
Cl-BP, 8-hr or 12-hr TWA (|)|)IT|)
LAD Cl-BP, 8-hr or 24-hr TWA
(ppm)
Central
Tendency
High-end
Central
Tendency
High-end
Manufacture
-
Worker
9.00E-02
2.70E-01
3.58E-02
1.38E-01
Median, Maximum
Monitoring Data
Import, Processing as a
Reactant, Processing -
Incorporation into
Articles, Repackaging
-
Worker
3.83E-3
5.67E-2
1.52E-3
2.91E-2
N/A - CT and HE b
Model
(Deterministic)
Processing -
Incorporation into
Formulation
-
Worker
7.20E+00
2.86E+00
N/A (1 data point)
Monitoring Data
-
ONU
1.55E-01
2.76E-01
6.16E-02
1.41E-01
50th and 95th Percentile
Batch Vapor
Degreaser (Open-Top)
-
Worker
6.70E+00
4.94E+01
2.66E+00
2.53E+01
50th and 95th Percentile
Monitoring Data
-
ONU
2.00E-02
2.15E+00
7.95E-03
1.10E+00
Pre-EC
Worker
1.89E+00
2.39E+01
7.04E-01
9.19E+00
50th and 95th Percentile
Model
(Probabilistic)
Post-EC
Worker
1.89E-01
2.39E+00
7.04E-02
9.19E-01
Pre-EC
ONU
9.93E-01
1.35E+01
3.71E-01
5.23E+00
Post-EC
ONU
9.93E-02
1.35E+00
3.71E-02
5.23E-01
Batch Vapor
Degreaser (Closed-
loop)
-
Worker
3.78E-02
4.78E-01
1.41E-02
1.84E-01
50th and 95th Percentile
Model
(Probabilistic)
-
ONU
1.99E-02
2.70E-01
7.43E-03
1.05E-01
Cold Cleaner
-
Worker
4.30E+00
7.40E+00
1.71E+00
3.79E+00
Median, Maximum
Monitoring Data
-
ONU
2.60E+00
1.03E+00
1.33E+00
N/A (1 data point)
-
Worker
5.49E-01
1.19E+01
2.06E-01
4.59E+00
50th and 95th Percentile
Model
(Probabilistic)
-
ONU
2.89E-01
6.83E+00
1.08E-01
2.63E+00
Aerosol Spray
Degreaser/Cleaner
Pre-EC
Worker
1.61E+01
3.16E+01
6.38E+00
1.62E+01
50th and 95th Percentile
Monitoring Data
Post-EC
Worker
5.50E+00
2.19E+00
2.82E+00
N/A (1 data point)
-
Worker
6.37E+00
2.25E+01
2.38E+00
9.05E+00
50th and 95th Percentile
Model
(Probabilistic)
-
ONU
1.10E-01
9.30E-01
4.00E-02
3.60E-01
Adhesive Chemicals
(Spray Adhesive)
Pre-EC
Sprayer
1.33E+02
2.54E+02
5.28E+01
1.30E+02
50th and 95th Percentile
Monitoring Data
Post-EC
Sprayer
1.78E+01
4.19E+01
7.08E+00
2.15E+01
Page 126 of 486
-------
TWA Exposures
Chronic, Cancer Exposures
Statistical Value for
Central Tendency
and High-end
Condition of Use
Exposure
Scenario
Category
Cl-BP, 8-hr or 12-hr TWA (|)|)IT|)
LAD Cl-BP, 8-hr or 24-hr TWA
(ppm)
Data Type
Central
Tendency
High-end
Central
Tendency
High-end
Pre-EC
Non-Sprayer
1.27E+02
2.11E+02
5.06E+01
1.08E+02
Post-EC
Non-Sprayer
1.80E+01
2.88E+01
7.15E+00
1.48E+01
Pre-EC
ONU
3.00E+00
1.29E+02
1.19E+00
6.60E+01
Post-EC
ONU
2.00E+00
5.48E+00
7.95E-01
2.81E+00
-
Worker
2.94E+01
5.02E+01
1.17E+01
2.57E+01
50th and 95th Percentile
Monitoring Data
-
ONU
1.21E+01
2.06E+01
4.80E+00
1.06E+01
3rd Gen
Spot Cleaner
2.93E+00
7.93E+00
3.94E-01
1.14E+00
3rd Gen
Machine &
Finish
1.41E+01
6.05E+01
1.89E+00
8.57E+00
Dry Cleaning
3rd Gen
ONU
1.82E+00
6.65E+00
2.43E-01
9.49E-01
3rd Gen
Child
5.41E-01
4.03E+00
N/A
N/A
50th and 95th Percentile
Modela
4th Gen
Spot Cleaner
2.40E+00
5.65E+00
3.20E-01
8.22E-01
(Probabilistic)
4th Gen
Machine &
Finish
2.38E+00
6.36E+00
3.15E-01
9.35E-01
4th Gen
ONU
1.31E+00
4.21E+00
1.73E-01
5.96E-01
4th Gen
Child
8.96E-02
1.02E+00
N/A
N/A
Spot Cleaner, Stain
Remover
-
Worker
9.00E-01
4.73E+00
3.58E-01
2.42E+00
Monitoring Data
-
Worker
3.24E+00
7.03E+00
2.89E-01
6.82E-01
50th and 95th Percentile
Model
-
ONU
1.63E+00
4.68E+00
1.45E-01
4.45E-01
(Probabilistic)
Disposal, Recycling
-
Worker
3.83E-3
5.67E-2
1.52E-3
2.91E-2
N/A - CT and HE b
Model
(Deterministic)
a - For this condition of use, the acute concentration (AC) and chronic, non-cancer exposure (ADC) differ from the TWA exposure. See previous subsections for AC and
ADC values.
b - Based on distinct model scenarios that are likely representative of central tendency (CT) and high-end (HE) exposures.
Page 127 of 486
-------
2.3.1.23 Dermal Exposure Assessment
Dermal absorption of 1-BP depends on the type and duration of exposure. Where exposure is non-
occluded, only a fraction of 1-BP that comes into contact with the skin will be absorbed as the chemical
readily evaporates from the skin (see Section 1.1). However, dermal exposure may be increased in cases
of occluded exposure, repeated contacts, or dermal immersion. For example, work activities with a high
degree of splash potential may result in 1-BP liquids trapped inside the gloves, inhibiting the
evaporation of 1-BP and increasing the exposure duration.
To assess exposure, EPA used the Dermal Exposure to Volatile Liquids Model (see following equation)
to calculate the dermal retained dose. The equation modifies EPAOPPT 2-HandDermal Exposure to
Liquids Model (peer reviewed) by incorporating a "fraction absorbed (fabs)" parameter to account for the
evaporation of volatile chemicals and a "protection factor (PF)" to account for glove use:
Equation 2-2. Equation for Calculating Occupational Dermal Exposure
rj S x( Qu x/abs)x Ydermx FT
exp ~ pF
Where:
Dexp is the dermal retained dose (mg/kg-day)
S is the surface area of contact (Default: 535 cm2 for central tendency and 1,070 cm2 for high-end
scenario, equivalent to the total surface area of one and two hands, respectively)
Qu is the quantity remaining on the skin after an exposure event (Default: 1.4 mg/cm2-event for central
tendency and 2.1 mg/cm2-event for high-end scenario27)
Yderm is the weight fraction of the chemical of interest in the liquid (0 < Yderm < 1)
FT is the frequency of events (integer number per day)
fabs is the fraction of applied mass that is absorbed (Default for 1-BP: 0.0029)
PF is the glove protection factor (Default: see Table 2-28)
In a 2011 in vitro dermal penetration study, Frasch et al. (2011) measured a 1-BP fractional absorption
(fabs) of 0.16 percent in a non-occluded, finite dose scenario. The author noted a large standard deviation
in the experimental measurement, which is indicative of the difficulty in spreading a small, rapidly
evaporating dose of 1-BP evenly over the skin surface. The measurement was performed in an open
fume hood with an average air speed of 0.3 m/s (30 cm/s), a wind speed higher than those typically
experienced in an indoor workplace. At a more typical indoor wind speed of 12.2 cm/s, the 1-BP
fractional absorption can be adjusted to 0.29 percent. Detailed calculations of this adjusted value are
provided in Appendix D.
27 Value for Qu is derived from experimental studies of liquid with varying viscosities. The 50th and 90th percentile value of
this distribution correspond to 1.4 and 2.1 mg/cm2, respectively, and are the default values for the Dermal Exposure to
Volatile Liquids Model.
Page 128 of 486
-------
Default glove PF values, which vary depending on the type of glove used and the presence of employee
training program, are shown in Table 2-28. 1-BP easily travels through most glove materials.
Recommended glove materials for protection against 1-BP are supported polyvinyl alcohol or multiple-
layer laminates (OSHA. 2013c).
Table 2-28. Glove Protection Factors for Different Dermal Protection Strategies
Dermal Protection Characteristics
Setting
Protection Factor, PF
a. No gloves used, or any glove / gauntlet without permeation data and
without employee training
Industrial and
Commercial Uses
1
b. Gloves with available permeation data indicating that the material of
construction offers good protection for the substance
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 Uses Only
20
Source: (Marquart et al.. 2017)
Table 2-29 presents the estimated dermal retained dose for workers in various exposure scenarios,
including what-if scenarios for glove use. The exposure estimates assume one exposure event (applied
dose) per work day and that 0.29 percent of the applied dose is absorbed through the skin. The exposure
estimates are provided for each condition of use, where the conditions of uses are "binned" based on the
maximum possible exposure concentration (Yderm) and the likely level of exposure. The exposure
concentration is determined based EPA's review of currently available products and formulations
containing 1-BP. For example, EPA found that 1-BP concentration in degreasing formulations such as
Solvon PB can be as high as 97 percent:
• Bin 1: Bin 1 covers industrial uses that generally occur in closed systems. For these uses, dermal
exposure is likely limited to chemical loading/unloading activities (e.g., connecting hoses) and
taking quality control samples.
• Bin 2: Bin 2 covers industrial degreasing uses, which are not closed systems. For these uses, there is
greater opportunity for dermal exposure during activities such as charging and draining degreasing
equipment, drumming waste solvent, and removing waste sludge.
• Bin 3: Bin 3 covers the use of 1-BP in spray adhesives in foam cushion product manufacturing,
which is a unique condition of use. Workers (sprayers) can be dermally exposed when mixing
adhesive, charging adhesive to spray equipment, and cleaning adhesive spray equipment. Other
workers (non-sprayers) may also have incidental contact with the applied adhesive during
subsequent fabrication steps.
• Bin 4: Bin 4 covers commercial activities of similar maximum concentration. Most of these uses are
uses at dry cleaners, and/or uses expected to have direct dermal contact with bulk liquids. At dry
cleaning shops, workers may be exposed to bulk liquids while charging and draining solvent to/from
machines, removing and disposing sludge, and maintaining equipment. Workers can also be exposed
to 1-BP used in spot cleaning products at the same shop.
Page 129 of 486
-------
• Bin 5: Bin 5 covers aerosol uses, where workers are likely to have direct dermal contact with film
applied to substrate and incidental deposition of aerosol to skin. This bin also covers miscellaneous
non-aerosol applications that are typically niche uses of 1-BP.
As shown in the table, the calculated retained dose is low for all non-occluded scenarios as 1-BP
evaporates quickly after exposure. Dermal exposure to liquid is not expected for occupational non-users,
as they do not directly handle 1-BP.
EPA also considered potential dermal exposure in cases where exposure is occluded. See further
discussion on occlusion in the Supplemental Information on Occupational Exposure Assessment (EPA.
2019a
Strength, Limitation, and Uncertainty of the Dermal Exposure Assessment
Dermal exposures are assessed using the Dermal Exposure to Volatile Liquids Model, which relies on
the Frasch et al. (2011) study to determine fractional absorption in accounting for chemical
volatilization. Although the study presents 1-BP specific measurement, the study also noted a large
standard deviation in the measured value. In addition, the underlying EPA dermal model assumes one
exposure event per day, which likely underestimates exposure as workers often come into repeat contact
with the chemical throughout their work day. Based on the uncertainties described above, EPA has a
medium level of confidence in the assessed baseline exposure.
Glove protection factors are presented as what-if scenarios to show the potential effect of glove use on
exposure levels. The actual frequency, type, and effectiveness of glove use in specific workplaces with
1-BP conditions of use are uncertain.
Page 130 of 486
-------
Table 2-29. Estimated Dermal Retained Dose for Workers in All Conditions of Use
Condition of Use
Bin
Max
Yderm
Dermal Exposure (mg/day)
No Gloves
(PF = 1)
Protective Gloves
(PF = 5)
Protective Gloves
(PF = 10)
Protective Gloves
(Industrial uses,
PF = 20)
Manufacture
Import, Repackaging
Processing - Incorporating into
formulation
Processing as a reactant
Processing - Incorporating into articles
Recycling
Disposal
Bin 1
1.0
2.2 (CT)
6.5 (High-end)
0.4 (CT)
1.3 (High-end)
0.2 (CT)
0.7 (High-end)
0.1 (CT)
0.3 (High-end)
Use - Batch Vapor Degreaser
Use - In-line Vapor Degreaser
Use - Cold Cleaner
Bin 2
0.97
2.1 (CT)
6.3 (High-end)
0.4 (CT)
1.3 (High-end)
0.2 (CT)
0.6 (High-end)
0.1 (CT)
0.3 (High-end)
Use - Adhesive Chemicals (Spray
Adhesives)
Bin 3
0.8
1.7 (CT)
5.2 (High-end)
0.3 (CT)
1.0 (High-end)
0.2 (CT)
0.5 (High-end)
N/A
Use - Dry Cleaning
Use - Spot Cleaner, Stain Remover
Bin 4
0.94
2.0 (CT)
6.1 (High-end)
0.4 (CT)
1.2 (High-end)
0.2 (CT)
0.6 (High-end)
N/A
Use - Other non-aerosol uses
Use - Aerosol Spray
Degreaser/Cleaner, Other aerosol uses
Bin 5
1.0
2.2 (CT)
6.5 (High-end)
0.4 (CT)
1.3 (High-end)
0.2 (CT)
0.7 (High-end)
N/A
Page 131 of 486
-------
2,3.2 Consumer Exposures
EPA evaluated 1-BP exposure resulting from the use of consumer products within a residence.
EPA utilized a modeling approach to evaluate exposure because chemical specific personal
monitoring data was not identified for consumers during data gathering and literature searches
performed as part of systematic review.
Table 2-30 summarizes the consumer conditions of use from Table 1-4 and the associated
consumer conditions of use assessed in this evaluation.
Table 2-30. Consumer Conditions of Use Assessed in This Risk Evaluation
Life-Cycle Stage
Category
Subcategory
Assessed Condition of Use
Consumer Uses
Solvent (for
cleaning or
degreasing)
Aerosol spray degreaser/cleaner
Section 2.3.2.2.1- Aerosol spray
degreaser/cleaner - general
Section 2.3.2.2.2- Aerosol spray
degreaser/cleaner - electronics
Cleaning and
furniture care
products
Spot cleaner, stain remover
Section 2.3.2.2.3 - Spot cleaner/stain
remover
Liquid cleaner (e.g., coin and
scissors cleaner)
Section 2.3.2.3.1- Coin and scissors
cleaner
Liquid spray/aerosol cleaner
Section 2.3.2.2.4 - Spray cleaner -
general
Other uses
Arts, crafts and hobby materials -
adhesive accelerant
Section 2.3.2.2.5 - Adhesive
accelerant
Automotive care products -
refrigerant flush
Section 2.3.2.3.2 - Automobile AC
flush
Anti-adhesive agents - mold
cleaning and release product
Section 2.3.2.2.6 Mold cleaning and
release product
Building/construction materials not
covered elsewhere - insulation
Section 2.3.2.4.1 and Section
2.3.2.4.2 - Insulation (off-gassing)
2.3.2.1 Consumer Exposures Approach and Methodology
Consumer products containing 1-BP are readily available at retail stores and via the internet for
purchase and use. Use of these products can result in consumer exposure to 1-BP during and after
product use. This assessment quantitatively evaluates consumer exposure to 1-BP for the consumer
user and bystander within a residence. For purposes of this assessment, consumer user is the
receptor using a product containing 1-BP within a residence in a specified room of use. The
consumer bystander is the receptor within the residence where a product containing 1-BP is used
but outside the specified room of use during product use. This assessment qualitatively evaluates
consumer exposure for potentially exposed susceptible subpopulations (PESS).
Product Identification
Consumer products containing 1-BP were identified through review and searches of a variety of
sources, including the National Institutes of Health (NIH) Household Products Database, various
government and trade association sources for products containing 1-BP, company websites for
Page 132 of 486
-------
Safety Data Sheets (SDS), Kirk-Othmer Encyclopedia of Chemical Technology, and the internet in
general. These consumer products are summarized in thq Preliminary Information on
Manufacturing, Processing, Distribution, Use, and Disposal: 1-Bromopropane document (U.S.
EPA. 2017c! put together by EPA and included in the docket for this final evaluation (Docket
Number EPA-HQ-OPPT-2016-0741 -0003V This Preliminary Information on Manufacturing,
Processing, Distribution, Use, and Disposal: 1-Bromopropane document (U.S. EPA. 2017c) may
not be a complete list of all consumer products available at the time of the searches because not all
SDS display a complete list of chemical ingredients, therefore some products may contain 1-BP
but cannot be confirmed by EPA. This Preliminary Information on Manufacturing, Processing,
Distribution, Use, and Disposal: 1-Bromopropane document (U.S. EPA. 2017c) is representative
of information found at the time of the searches and is considered reasonably available
information; but does not take into consideration company-initiated formulation changes, product
discontinuation, or other business or market based factors that occurred after the document was
compiled.
Models Used and Routes of Exposure Assessed
Three models were used to evaluate consumer inhalation exposure to 1-BP for this assessment,
EPA's Consumer Exposure Model (CEM), EPA's Multi-Chamber Concentration and Exposure
Model (MCCEM), and EPA's Indoor Environment Concentrations in Buildings with Conditioned
and Unconditioned Zones (IECCU) model. These models can be found through the following link
https://www.epa.gov/tsca-screening-tools/approaches-estimate-consumer-exposure-under-tsca.
Two models were used to evaluate consumer dermal exposure to 1-BP for this assessment, EPA's
CEM (Permeability) method and CEM (Fraction Absorbed). Table 2-31 summarizes the assessed
consumer conditions of use (COUs), the routes of exposure assessed, and the models used for the
assessment of each condition of use.
Table 2-31. Consumer Conditions of Use (COUs) and Routes of Exposure Assessed
Assessed COUs
Routes of Exposure
Inhalation
Dermal
Aerosol Spray Degreaser/Cleaner-General
CEM
CEM (Permeability)
Aerosol Spray Degreaser/Cleaner-Electronics
CEM
CEM (Fraction Absorbed)
Spot Cleaner and Stain Remover
CEM
CEM (Permeability)
Coin and Scissors Cleaner
MCCEM
CEM (Permeability)
Spray Cleaner-General
CEM
CEM (Permeability)
Adhesive Accelerant
CEM
CEM (Fraction Absorbed)
Automobile AC Flush
MCCEM
CEM (Fraction Absorbed)
Mold Cleaning and Release Product
CEM
CEM (Fraction Absorbed)
Insulation (Off-gassing)
IECCU
N/A
Inhalation
Reasonably available information on the toxicity profile and physicochemical properties of 1-BP
support inhalation as an expected route of exposure for human health associated with consumer
product uses. Consumer user and bystander inhalation exposure to 1-BP can occur through direct
Page 133 of 486
-------
inhalation of vapors, mists, and aerosols (e.g., aerosols from spray applications) during product use
as well as indirect inhalation of 1-BP following application and evaporation (e.g., as products dry
and evaporate from surfaces to which it is applied or a pool of product during use). The magnitude
of inhalation exposure depends on a variety of factors including the concentration of 1-BP in
products used, use patterns (including frequency, duration, amount of product used, room of use,
and local ventilation), and application methods.
While inhalation exposure can be acute or chronic in nature, EPA does not expect consumer
exposure to be chronic in nature because product use patterns tend to be infrequent with relatively
short durations of use. The one exception, among the nine consumer COUs identified in Table
2-31, is the insulation (off-gassing) scenario which involves both an acute exposure (short
duration, high concentration exposure following initial installation) and a chronic exposure (long
duration, low concentration exposure for years following initial installation). Therefore, this
assessment evaluates acute inhalation exposure for all nine consumer COUs identified in Table
2-31 and chronic inhalation exposure for the insulation (off-gassing) scenario.
Dermal
Dermal exposure is a reasonably foreseeable exposure route associated with consumer product use.
Consumer dermal exposure to 1-BP resulting from product use occurs via liquid, vapor or mist
deposition onto the skin or direct contact with material during product use or after application (e.g.,
immersion of a body part into a pool of product or placing an unprotected body part on a surface
prior to the surface fully drying following product application to that surface). The magnitude of
dermal exposure depends on several factors including skin surface area, product volume,
concentration of 1-BP in products used, and dermal exposure duration. The potential for dermal
exposure to 1-BP is limited by several factors including physical-chemical properties of 1-BP, high
vapor pressure, and expected quick volatilization of product containing 1-BP from surfaces.
There is limited toxicological data available for the dermal route of exposure, and no toxicokinetic
information is available to develop physiologically-based pharmacokinetic models. While dermal
exposure can be acute or chronic in nature, EPA does not expect consumer dermal exposure to be
chronic in nature because product use patterns tend to be infrequent with relatively short durations
of use. Although 1-BP is volatile, EPA evaluated dermal exposure for all consumer COUs
identified in Table 2-31 except the Insulation (off-gassing) COU since dermal exposure is not
expected to occur from rigid insulation board off-gassing. EPA used the CEM (Permeability)
model to evaluate dermal exposure for those COUs where there is the possibility of a continuous
supply of chemical against the skin with inhibited or prohibited evaporation potential due to a
barrier or direct immersion of body parts into a product during use. EPA used the CEM (Fraction
Absorbed) model for the remaining COUs where evaporation is expected to be uninhibited and no
direct immersion of body parts into a product occurs during use.
Populations Evaluated
This assessment quantitatively evaluates inhalation and dermal exposures to 1-BP for the consumer
user and inhalation exposures to 1-BP for the bystander within a residence. Consumer users, for
Page 134 of 486
-------
this evaluation, are assumed to be male and female youth (between 11 and 21 years of age) and
male and female adults (21 years of age and greater). Consumer users include men and women of
reproductive age. The consumer user is the individual using a product containing 1-BP within a
residence in a specified room of use. The consumer user remains within the specified room of use
during product use. Following product use, a consumer user may remain in the room of use for a
certain period of time, leave the room of use, or go in and out of the room of use for the remainder
of the day depending on their activity pattern.
Bystanders, for this evaluation, can be male or female individuals in any age group ranging from
infants (less than one year of age) to adults. Bystanders include men and women of reproductive
age as well as infants, toddlers, children at various developmental stages in life, and elderly. The
consumer bystander is the receptor within the residence where a product containing 1-BP is used
but remains outside the specified room of use during product use. Following product use, a
bystander may remain outside the room of use for a certain period of time or go in and out of the
room of use for the remainder of the day depending on their activity pattern.
2.3.2.2 Consumer Exposure Model (CEM) - Overview, Approach, Inputs, and
Results
Overview
The CEM predicts indoor air concentrations from consumer product use through a deterministic,
mass-balance calculation derived from emission calculation profiles within the model. It is a peer
reviewed EPA model which relies on user provided input parameters, various assumptions, and
several default inputs to generate exposure estimates. The defaults within CEM are a combination
of high-end and mean/central tendency values from published literature, other studies, and values
taken from U.S. EPA's Exposure Factors Handbook (U.S. EPA. 2011). The CEM has built in
flexibility which allows the modeler to modify certain default values when chemical specific
information is available. The CEM also allows the modeler to select, if desired, an option for CEM
to provide a time series air concentration profile (intermediate concentration values produced prior
to applying pre-defined activity patterns) for each run. The CEM does not require chemical -
specific emissions data, which may be required to run more complex consumer models, but does
provide the modeler the opportunity to input certain chemical-specific emissions data (like
background concentrations) when desired. Readers can learn more about the CEM, equations
within the models, detailed input and output parameters, pre-defined scenarios, default values used,
and supporting documentation by reviewing the CEM user guide (U.S. EPA. 2019a) and CEM user
guide appendices (U.S. EPA. 2019b).
Approach and Inputs
There are six emission calculation profiles (E1-E6), three inhalation models (P INHl, P INH2,
and A INHl), and seven dermal models (PDERl, P_DER2a, P_DER2b, P DER3, A DERl,
ADER2, and ADE3) within CEM. There are also seventy-three specific product and article
categories and several generic product categories with pre-defined default values within CEM. All
consumer COUs for which exposure was assessed with the CEM utilized the Generic Product E3
Page 135 of 486
-------
(+ Vapor to Skin) product category except the coin and scissors cleaner COU which used the
Generic Product E5 (+ Vapor to Skin) product category. All six of the consumer COUs for which
inhalation exposure was assessed with the CEM utilized the PINH2 inhalation model. All
consumer COUs identified in Table 2-31 for which dermal exposure was assessed with the CEM
(Permeability) model utilized the P_DER2b dermal model. The consumer COUs identified in
Table 2-31 for which dermal exposure was assessed with the CEM (Fraction Absorbed) model
utilized the P_DER2a model.
E3 (Emission from Product Sprayed): This profile assumes a small percentage of a product is
aerosolized (e.g., overspray) and therefore immediately available for uptake by inhalation. The
remainder of product is assumed to contact the target surface and later volatilize at a rate that
depends on the chemical's molecular weight and vapor pressure. The aerosolized portion of
product is treated using a constant emission rate model. The remaining portion of the product (non-
aerosolized) is treated in the same manner as products applied to a surface (combining a constant
application rate with an exponentially declining rate for each instantaneously applied segment).
E5 (Emission from Product Placed in Environment) : This model assumes emission at a constant
rate over a duration that depends on the chemical's molecular weight and vapor pressure. If this
duration exceeds the user specified duration of use, then the chemical emissions are truncated at
the end of the product use period, because the product is assumed to be removed from the house
after the use period.
P INH2 (Inhalation of Product Used in Environment; Near Field/Far Field): This model predicts
indoor air concentrations from product use utilizing the associated emission profile (E1-E5) and a
two-zone representation of the building of use (Zone 1 and Zone 2). Zone 1 represents the room
where the consumer product is used while Zone 2 represents the remainder of the building of use.
This model further divides Zone 1 into Zone 1 near-field and Zone 1 far-field to accommodate
situations where a higher concentration of product is expected very near the product user during
product use. The Zone 1 near-field can be represented as a bubble around the product user which
moves throughout the room of use with the product user. The Zone 1 far-field represents the
remainder of the room of use (Zone 1). Product users inhale airborne concentrations estimated
within the Zone 1 near-field during product use and Zone 1 far-field following product use while
the product user remains in the room of use.
P DER2a (Dermal Dose from Product Applied to Skin, Fraction Absorbed Model): This model
uses an absorption coefficient to estimate dermal exposure based on the absorbed dose of a
chemical from a thin film applied onto the skin. This methodology assumes the application of the
chemical of concern (or product containing the chemical of concern) occurs once to a specific film
thickness. Utilizing an assumption that the entire mass of the chemical in the thin film enters the
skin, this model then estimates the absorbed dose by applying the absorption coefficient to the
entire mass of chemical within the skin. This model essentially measures two competing processes,
evaporation of the chemical from the skin and penetration of the chemical deeper into the skin, and
therefore is more applicable to conditions of use where evaporation is uninhibited and full
immersion of body parts does not occur during use.
Page 136 of 486
-------
P DER2b (Dermal Dose from Product Applied to Skin, Permeability Model): This model uses a
skin permeability coefficient to estimate dermal exposure based on potential or absorbed doses for
products that come in direct contact with the skin. The permeability coefficient can be a user
defined value (if available for the chemical of concern) or estimated using the built in permeability
estimator within CEM. This model is based on the ability of a chemical to penetrate the skin layer
once contact occurs. This model assumes a constant supply of chemical, directly in contact with
the skin, throughout the exposure duration. This model does not consider evaporative losses in its
estimates of dermal exposure and therefore is more representative of a dermal exposure condition
where evaporation is limited or prohibited due to direct immersion of skin into a product or use of
a product soaked rag or other barrier that is in direct contact with unprotected skin during product
use.
EPA utilized the time-series indoor air concentration option within the CEM. This provided
concentrations in 30-second increments across the entire time period simulated in each run (72
hours). EPA also utilized the near-field/far-field option within the CEM. Use of these two options
together provided EPA with zone specific concentrations (Zone 1 near-field, Zone 1 far-field, and
Zone 2) to which a stay-at-home activity pattern was applied for the user and bystander during
post-processing within Microsoft Excel. A rolling 24-hour time-weighted average (TWA)
concentration was calculated for each personal exposure time series (user and bystander). The
maximum 24-hour time-weighted average (TWA) was then identified and extracted as the
exposure concentration.
Numerous input parameters are required to generate exposure estimates within the CEM. These
parameters include physical-chemical properties of the chemical of concern, product information
(e.g., density, water solubility, vapor pressure), model selection and scenario inputs (e.g.,
pathways, emission model(s), emission rate, activity pattern), product or article property inputs
(e.g., frequency of use, fraction of product aerosolized), environmental inputs (e.g., building
volume, room of use, air exchange rates), and receptor exposure factor inputs (e.g., body weight,
exposure duration, inhalation rate).
To characterize a potential range of consumer user and bystander exposures, modeling efforts
involved varying select parameters across a range of values found in the literature. EPA identified
parameters to vary based on the sensitivity of the CEM to the parameters, the parameters
representativeness of consumer behavior patterns for product use, and availability of a range of
values within published literature.
A sensitivity analysis was conducted on the CEM and is provided in the CEM User Guide
Appendices (U.S. EPA. 2019b). EPA reviewed the sensitivity analysis to identify key parameters
to which the CEM is both sensitive to and representative of consumer behavior patterns for product
use. EPA then cross referenced these key parameters with those found in literature and other
sources (captured and evaluated as part of the systematic review process) to identify the
availability of a range of values for those parameters. Based on this effort, EPA identified the
following three key parameters to vary for modeling purposes:
1) Duration of use per event (minutes/use),
Page 137 of 486
-------
2) Mass of product used per event (gram(s)/use), and
3) Amount of chemical in the product (weight fraction).
Each of these three parameters were modeled at three points across the range of values found in the
literature. More specifically, duration of use per event and mass of product used per event were
modeled at the 10th, 50th, and 95th percentile values extracted from an EPA directed survey of
consumer behavior patterns in the United States titled Household Solvent Products: A National
Usage Survey (EPA. 1987) (Westat Survey). This survey is a nationwide survey which provides
information on product usage habits for thirty-two different product categories. The information
for this survey was collected via questionnaire or telephone from 4,920 respondents across the
United States. The Westat Survey was rated as a high quality study during data evaluation within
the systematic review process.
The amount of chemical in the product(s) was modeled at the minimum, mid, and maximum values
extracted from product specific Safety Data Sheets (SDS). Modeling three key parameters across
three range values results in a maximum of twenty-seven different iterations for each condition of
use assessed with the CEM in this evaluation [See Appendix F for a table summarizing the 27
iterations].
Additional input parameters for the consumer COUs evaluated with the CEM are discussed below.
Detailed tables of all input parameters for each use evaluated with the CEM are provided in the 1-
BP Supplemental File: Information on Consumer Exposure Assessment Model Input Parameters
(EPA. 2019a).
Non- Varied Input Parameters
Physical-chemical properties of 1-BP were kept constant across all conditions of use modeled and
all iterations. The vapor pressure of 1-BP applied for modeling was 110.8 Torr. The saturation
concentration of 1-BP in air was estimated by the CEM as 9.66E+05 milligrams per cubic meter
(mg/m3).
A neat-based, chemical-specific, skin permeability coefficient was calculated from literature and
experimental data identified and evaluated as part of EPA's systematic review process (Frasch et
al.. 2011) and the 1992 EPA Dermal Exposure Assessment: Principles and Applications (U.S.
EPA. 1992). The calculated skin permeability coefficient of 4.62E-04 centimeters per hour (cm/hr)
was utilized for all COUs evaluated using the CEM (Permeability) model for dermal exposure.
A measured experimental fraction absorbed term was identified within the literature (Frasch et al..
2011) and evaluated as part of EPA's systematic review process. The measured fraction absorbed
term was adjusted for air speed due to experimental conditions under which it was obtained. The
adjusted value of 0.0029 was utilized for all COUs evaluated using the CEM (Fraction Absorbed)
model for dermal exposure.
The activity pattern selected for modeling consumer user and bystander exposures in this
evaluation was stay-at-home with a start time for product use of 9:00 AM. Frequency of use for
acute exposure calculations was held constant at one event per day. The building volume used for
Page 138 of 486
-------
all conditions of use modeled for all iterations was the CEM default value of 492 m3 from the 2011
U.S. EPA Exposure Factors Handbook (U.S. EPA. 2011). The near-field volume selected for all
conditions of use modeled for all iterations was one cubic meter to represent the immediate
breathing zone of the consumer user. The aerosol fraction (overspray fraction) immediately
available for uptake via inhalation was set at six percent based on a review of the literature. The
background concentration of 1-BP was assumed to be negligible and therefore set at zero.
Conditions of Use Specific Input Parameters
Certain input parameters were varied across different conditions of use modeled, but kept constant
for all iterations run for that particular condition of use. These condition of use specific input
parameters include, product densities, room of use, and volume of room of use. Product densities
were extracted from product-specific SDS and varied by product type. The room of use was
extracted from the Westat Survey (EPA 1987) based on a cross-walk EPA developed between
each 1-BP condition of use modeled and comparable Westat Survey product categories. This
crosswalk is summarized in Table 2-32.
Table 2-32. Crosswalk Between 1-BP Conditions of Use and Westat Product Category
1-BP Condition of Use
Representative Westat Product Category
1. Aerosol Spray Degreaser/Cleaner-General
Engine Degreasers
2. Aerosol Spray Degreaser/Cleaner-Electronics
Specialized Electronics Cleaners (TV, VCR Razor, etc.)
3. Spot Cleaner and Stain Remover
Spot Removers
4. Coin and Scissors Cleaner
Not Applicable
5. Spray Cleaner-General
Solvent Type cleaning Fluids or Degreasers
6. Adhesive Accelerant
Contact Cement, Super Glues, and Spray Adhesives
7. Automobile AC Flush
Not Applicable
8. Mold Cleaning and Release product
Solvent Type Cleaning Fluids or Degreasers
9. Insulation (Off-gassing)
Not Applicable
The room of use selected for each condition of use modeled for this evaluation is based on the
room in which the Westat Survey results reported the highest percentage of respondents last used a
product within the room. When the Westat Survey identified the room of use where the highest
percentage of respondent last used the product as "other inside room," the utility room was selected
within the CEM for modeling purposes. The volume of the selected room of use varied based on
the room of use selected and ranged from 20 to 90 m3. The volume of the selected room is based
on default volumes within the CEM.
Scenario Specific Input Parameters
Three key input parameters were varied across both conditions of use modeled and all iterations
run for that particular condition of use. The duration of use per event and mass of product used per
event were extracted from the Westat Survey based on the associated condition of use to which it is
cross-walked. The extracted data represents the tenth, fiftieth (median), and ninety-fifth percentile
data, as presented in the Westat Survey (EPA 1987). The amount of chemical in the product
(weight fraction) was extracted from product-specific SDS. This parameter was varied across the
Page 139 of 486
-------
given range of products within the same condition of use modeled. The values represent the
minimum, mid/mean, and maximum weight fractions across the set of products identified for each
condition of use. Under this approach, if three products were identified for a single condition of use
with the following 1-BP weight fraction(s) or ranges [50%, 50-80%, 90%], then the "minimum"
weight fraction would be represented by 50%, the "mid/mean" weight fraction would be
represented by (50+90)/2 or 70%, and the "maximum" weight fraction would be represented by
90%. Where SDS were only available for a single product with a single weight fraction or very
small range, or multiple products which only provided a single weight fraction or very small range,
a single weight fraction was used for modeling purposes. Table 2-33 summarizes the scenario
specific varied input parameters for the six conditions of use for which the CEM was used to
model inhalation exposure to 1-BP.
Table 2-33. Scenario Specific Varied Input Parameters for the CEM Inhalation Modeling
Consumer Use
Duration of Use
Mass of Product Used
Amount of Chemical In
Product
(minutes/use)
(gram(s)/use)
(weight fraction)
10th
50th
95th
10th
50th
95th
Low
Mean
High
Aerosol Spray
Degreaser/Cleaner-
General
5
15
120
111.86
445.92
1845.17
0.109
0.505
0.9505
Aerosol Spray
Degreaser/Cleaner-
Electronics
0.5
2
30
1.56
19.52
292.74
0.496
0.72
0.972
Spot Cleaner and
Stain Remover
0.5
5
30
9.76
51.91
434.43
0.276
0.58
0.922
Spray Cleaner-
General
2
15
120
21.86
126.86
1249.04
0.94
(Single)
Adhesive
Accelerant
0.5
4.25
60
1.20
9.98
172.45
0.99
(Single)
Mold Cleaning and
Release Product
0.5
2
30
3.84
21.14
192.21
0.32
0.6
0.915
Results
Modeling results for inhalation and dermal exposures evaluated with the CEM are summarized and
discussed below. Results are presented by condition of use. All results for all iterations modeled
are provided in the 1-BP Supplemental File: Information on Consumer Exposure Assessment
Model Outputs (EPA 2019b).
Results are presented in this section for three of the 27 possible iterations run for each condition of
use. Inhalation concentrations are presented in parts per million (ppm) while dermal doses are
presented as average daily doses (ADD) in milligrams of 1-BP per kilogram body weight per day
(mg/kg-day). The three iterations selected provide a range of exposure concentrations across each
condition of use modeled. Three descriptors are used in the results tables to represent the three
iterations presented. These descriptors are based on the three key input parameters varied during
Page 140 of 486
-------
modeling (duration of use per event, mass of product used per event, and amount of chemical in
product (weight fraction)) as follows:
High Intensity Use: Refers to the model iteration which utilizes the 95th percentile duration of use
per event and mass of product used per event (as presented in the Westat Survey (EPA. 1987)) and
the maximum amount of chemical in product (weight fraction) extracted from product specific
SDS.
Moderate Intensity Use: Refers to the model iteration which utilizes the median (50th percentile)
duration of use per event and mass of product used per event (as presented in the Westat Survey
(EPA. 1987)) and the mid/mean amount of chemical in product (weight fraction) extracted from
product specific SDS.
Low Intensity Use : Refers to the model iteration which utilizes the 10th percentile duration of use
per event and mass of product used per event (as presented in the Westat Survey (EPA. 1987)) and
the minimum amount of chemical in product (weight fraction) extracted from product specific
SDS.
Inhalation exposure is presented for two receptors (consumer user and bystander) utilizing a 24
hour time-weighted average. Dermal exposure is only presented for the consumer user as a
bystander is not expected to receive a dermal dose. Dermal exposure is presented for three age
groups Adult, Youth A, and Youth B utilizing an average daily dose.
• Adult: Male and female individuals 21 years of age and older.
• Youth A: Male and female individuals from 16 years of age through 20 years of age.
• Youth B: Male and female individuals from 11 years of age through 15 years of age.
These three age groups were evaluated because the CEM separates the Youth category into two
age brackets due to variability of exposure factors (like respiration rates, body weight, skin surface
area, and other factors) which can vary or change considerably during this developmental age
range. Although the Youth B age group includes individuals between 11 and 15 years of age, the
lower end of this age group (11-13) is a possible, but not necessarily reasonably foreseeable user of
these high solvent products, with the exception of the coin cleaner. However, the upper end of this
age group (14-15) is a possible and reasonably foreseeable user of all products whether it is using
cleaning products to complete chores within the residence, or learning basic automotive care or
other shop-type work like cleaning/degreasing items. Additionally, while certain products within a
general arts and crafts condition of use may include products like school glue, the only 1-BP
containing product identified within the arts and crafts condition of use for this evaluation is a
specialized, solvent-based adhesive accelerant. This product is not associated with a common
school glue and expected to be utilized by older, dedicated hobbyists for select projects where a
quicker curing of a separate adhesive is required or desired. Therefore, EPA does not include an
evaluation of dermal exposure to infants, toddlers, or children below the age of 11 for the arts and
crafts condition of use within this evaluation as they are not expected or intended users of such a
product.
Page 141 of 486
-------
2.3.2.2.1 Aerosol Spray Degreaser/Cleaner-General
This condition of use represents consumer uses of product as a solvent for cleaning or degreasing
in the form of an aerosol spray degreaser or cleaner. The products are used to dissolve oils, greases,
and similar materials from textiles, glassware, metal surfaces, and other articles. These products
are available to consumers with 1-BP concentrations ranging from 10 percent to 95 percent by
weight based on a review of product specific SDS. The room of use is the garage, based on the
results from the Westat Survey (EPA. 1987) product category cross-walked with this condition of
use. The duration of product use per event for these products ranges from 5 minutes to 120 minutes
based on the Westat Survey.
Table 2-34. Aerosol Spray Degreaser/Cleaner-General (Inhalation Exposure Concentrations)
Source Description
Parameters Varied
Exposed Receptor
24-hour TWA
Duration
Mass Used
Weight Fraction
(ppm)
(min)
(grams)
(percent)
High Intensity Use
95th
95th
Maximum
User
141
(120)
(1845.17)
(95.05)
Bystander
41
Moderate Intensity Use
50th
50th
Mean
User
19
(15)
(445.92)
(50.5)
Bystander
5
Low Intensity Use
10th
10th
Minimum
User
1.0
(5)
(111.86)
(10.9)
Bystander
0.25
Table 2-34 shows the inhalation exposure concentrations found for the low, moderate, and high
intensity use categories for this condition of use. The 24-hour TWA air concentrations of 1-BP for
the user varies from 1 ppm to 141 ppm. The 24-hour TWA air concentrations of 1-BP for the
bystander varies from 0.25 ppm to 41 ppm.
Dermal exposure was evaluated for this condition of use utilizing the CEM (Permeability) model
due to the possibility of a continuous supply of product on the skin and expected inhibited or
prohibited evaporation resulting from wiping with a product soaked rag during use. EPA used
inside of one hand as the area and body part exposed.
Table 2-35. Aerosol Spray Degreaser/Cleaner-General (Dermal Exposure Doses)
Source Description
Parameter Varied
Exposed Receptor
ADD
Duration
Mass Used
Weight
(mg/kg-day)
(min)
(grams)
Fraction
(Percent)
High Intensity Use
95th
95th
Maximum
Adult
3.5
(120)
(1845.17)
(95.05)
Youth A
3.3
Youth B
3.6
Moderate Intensity Use
50th
50th
Mean
Adult
0.23
(15)
(445.92)
(50.5)
Youth A
0.22
Youth B
0.24
Low Intensity Use
10th
10th
Minimum
Adult
1.7E-02
(5)
(111.86)
(10.9)
Youth A
1.6E-02
Youth B
1.7E-02
Page 142 of 486
-------
Table 2-35 shows the dermal exposure dose found for the low, moderate, and high intensity use
categories for this condition of use. The ADD of 1-BP for adults varies from 1.7E-02 mg/kg-day to
3.5 mg/kg-day. The ADD of 1-BP for Youth A varies from 1.6E-02 mg/kg-day to 3.3 mg/kg-day.
The ADD of 1-BP for Youth B varies from 1.7E-02 mg/kg-day to 3.6 mg/kg-day.
2.3.2.2.2 Aerosol Spray Degreaser/Cleaner-Electronics
This condition of use represents consumer uses of product as a solvent for cleaning or degreasing
in the form of an aerosol spray degreaser or cleaner for a more specialized category of electronic
degreasers. The products are used to dissolve oils, greases, and similar materials from textiles,
glassware, metal surfaces, and other articles. These products are available to consumers with 1-BP
concentrations ranging from 49 percent to 97 percent by weight based on a review of product
specific SDS. The room of use is the living room, based on the results from the Westat Survey
product category cross-walked with this condition of use. The duration of product use per event for
these products ranges from 0.2 minutes to 30 minutes based on the Westat Survey (EPA 1987).
However, due to a limitation on the minimum value available for duration of use within the CEM,
the low end value used for modeling this condition of use is 0.5 minutes.
At the time the Westat Survey (EPA 1987) was conducted, this type of product would typically be
used to clean consumer items like VCRs, cassette tape players, or early generation CD players.
There is an expectation that use of these types of degreasers/cleaners continues today, although the
consumer items cleaned may be more represented by DVD players or game
consoles/cassettes/cartridges contact areas. Items could also include computers and computer
motherboards, although some of these materials may be sensitive to such high solvent consumer
cleaning products. While water-based products are likely available, the high solvent consumer
cleaning products are still available for purchase and use.
Table 2-36. Aerosol Spray Degreaser/Cleaner-Electronics (Inhalation Exposure
Concentrations)
Source Description
Parameters Varied
Exposed Receptor
24-hour TWA
Duration
Mass Used
Weight Fraction
(ppm)
(min)
(grams)
(percent)
High Intensity Use
95th
95th
Maximum
User
30
(30)
(292.74)
(97.2)
Bystander
8.7
Moderate Intensity Use
50th
50th
Mean
User
1.4
(2)
(19.52)
(72)
Bystander
0.35
Low Intensity Use
10th
10th
Minimum
User
6.7E-02
(0.5)
(1.56)
(49.6)
Bystander
1.9E-02
Table 2-36 shows the inhalation exposure concentrations found for the low, moderate, and high
intensity use categories for this condition of use. The 24-hour TWA air concentrations of 1-BP for
the user varies from 6.6E-02 ppm to 30 ppm. The 24-hour TWA air concentrations of 1-BP for the
bystander varies from 1.9E-02 ppm to 8.7 ppm.
Page 143 of 486
-------
Dermal exposure was evaluated for this condition of use utilizing the CEM (Fraction Absorbed)
model due to the expectation of uninhibited evaporation and no full immersion of body parts into
the product during use. EPA used 10% of one hand as the area and body part exposed.
Table 2-37. Aerosol Spray Degreaser/Cleaner-Electronics (Dermal Exposure Doses)
Source Description
Parameter Varied
Exposed Receptor
ADD
Duration
Mass Used
Weight
(mg/kg-day)
(min)
(grams)
Fraction
(Percent)
High Intensity Use
95th
95th
Maximum
Adult
4.6E-02
(30)
(292.74)
(97.2)
Youth A
4.3E-02
Youth B
4.7E-02
Moderate Intensity Use
50th
50th
Mean
Adult
3.4E-02
(2)
(19.52)
(72)
Youth A
3.2E-02
Youth B
3.5E-02
Low Intensity Use
10th
10th
Minimum
Adult
2.4E-02
(0.5)
(1.56)
(49.6)
Youth A
2.2E-02
Youth B
2.4E-02
Table 2-37 shows the dermal exposure dose found for the low, moderate, and high intensity use
categories for this condition of use. The ADD of 1-BP for adults varies from 2.4E-02 mg/kg-day to
4.6E-02 mg/kg-day. The ADD of 1-BP for Youth A varies from 2.2E-02 mg/kg-day to 4.3E-02
mg/kg-day. The ADD of 1-BP for Youth B varies from 2.4E-02 mg/kg-day to 4.7E-02 mg/kg-day.
2.3.2.2.3 Spot Cleaner and Stain Remover
This condition of use represents consumer uses of a solvent product for cleaning and furniture care
in the form of spot cleaners or stain removers. The products are used to remove dirt, grease, stains,
and foreign matter from furniture and furnishings, or to cleanse, sanitize, or improve the
appearance of surfaces. These products are available to consumers with 1-BP concentrations
ranging from 27.6 percent to 92.2 percent by weight based on a review of product specific SDS.
The room of use is the utility room, based on the results from the Westat Survey product category
cross-walked with this condition of use. The duration of product use per event for these products
ranges from 0.3 minutes to 30 minutes based on the Westat Survey (EPA 1987). However, due to
a limitation on the minimum value available for duration of use within the CEM, the low-end value
used for modeling this condition of use is 0.5 minutes.
Page 144 of 486
-------
Table 2-38. Spot Cleaner and Stain Remover (Inhalation Exposure Concentrations)
Source Description
Parameters Varied
Exposed Receptor
24-hour TWA
Duration
Mass Used
Weight Fraction
(ppm)
(min)
(grams)
(percent)
High Intensity Use
95th
95th
Maximum
User
47
(30)
(434.43)
(92.2)
Bystander
7.2
Moderate Intensity Use
50th
50th
Mean
User
3.4
(5)
(51.91)
(58)
Bystander
0.54
Low Intensity Use
10th
10th
Minimum
User
0.26
(0.5)
(9.76)
(27.6)
Bystander
4.8E-02
Table 2-38 shows the inhalation exposure concentrations found for the low, moderate, and high
intensity use categories for this condition of use. The 24-hour TWA air concentrations of 1-BP for
the user varies from 0.26 ppm to 47 ppm. The 24-hour TWA air concentrations of 1-BP for the
bystander varies from 4.8E-02 ppm to 7.2 ppm.
Dermal exposure was evaluated for this condition of use utilizing the CEM (Permeability) model
due to the possibility of a continuous supply of product on the skin and expected inhibited or
prohibited evaporation resulting from wiping with a product soaked rag during use. EPA used
inside of one hand as the area and body part exposed.
Table 2-39. Spot Cleaner and Stain Remover (Dermal Exposure Doses)
Source Description
Parameter Varied
Exposed Receptor
ADD
Duration
(min)
Mass Used
(grams)
Weight
Fraction
(Percent)
(mg/kg-day)
High Intensity Use
95th
95th
Maximum
Adult
0.87
(30)
(434.43)
(92.2)
Youth A
0.81
Youth B
0.89
Moderate Intensity Use
50th
50th
Mean
Adult
9.1E-02
(5)
(51.91)
(58)
Youth A
8.5E-02
Youth B
9.3E-02
Low Intensity Use
10th
10th
Minimum
Adult
4.3E-03
(0.5)
(9.76)
(27.6)
Youth A
4.1E-03
Youth B
4.4E-03
Table 2-39 shows the dermal exposure dose found for the low, moderate, and high intensity use
categories for this condition of use. The ADD of 1-BP for adults varies from 4.3E-03 mg/kg-day to
0.87 mg/kg-day. The ADD of 1-BP for Youth A varies from 4.1E-03 mg/kg-day to 0.81 mg/kg-
day. The ADD of 1-BP for Youth B varies from 4.4E-03 mg/kg-day to 0.89 mg/kg-day.
2.3.2.2.4 Spray Cleaner-General
This condition of use represents consumer uses of solvent product for cleaning and furniture care
in the form of liquid spray and aerosol cleaners. The products are available to consumers as a
general purpose spray cleaner. These products are used to remove dirt, grease, and stains, or to
cleanse,, scour, polish, protect, or improve the appearance of surfaces. These products are
Page 145 of 486
-------
available to consumers, to be used as is, with 1-BP concentration of 94 percent by weight based on
a review of product specific SDS. The room of use is the utility room, based on the results from the
Westat Survey product category cross-walked with this condition of use. The duration of product
use per event for these products ranges from 2 minutes to 120 minutes based on the Westat Survey.
Table 2-40. Spray Cleaner-General (Inhalation Exposure Concentrations)
Source Description
Parameters Varied
Exposed Receptor
24-hour TWA
Duration
Mass Used
Weight Fraction
(ppm)
(min)
(grams)
(percent)
High Intensity Use
95th
95th
Single
User
133
(120)
(1249.04)
(94)
Bystander
33
Moderate Intensity Use
50th
50th
Single
User
14
(15)
(126.86)
(94)
Bystander
2.7
Low Intensity Use
10th
10th
Single
User
2.3
(2)
(21.86)
(94)
Bystander
0.44
Table 2-40 shows the inhalation exposure concentrations found for the low, moderate, and high
intensity use categories for this condition of use. The 24-hour TWA air concentrations of 1-BP for
the user varies from 2.3 ppm to 133 ppm. The 24-hour TWA air concentrations of 1-BP for the
bystander varies from 0.44 ppm to 33 ppm.
Dermal exposure was evaluated for this condition of use utilizing the CEM (Permeability) model
due to the possibility of a continuous supply of product on the skin and expected inhibited or
prohibited evaporation resulting from wiping with a product soaked rag during use. EPA used
inside of one hand as the area and body part exposed.
Table 2-41. Spray Cleaner-General (Dermal Exposure Doses)
Source Description
Parameter Varied
Exposed Receptor
ADD
Duration
Mass Used
Weight
(mg/kg-day)
(min)
(grams)
Fraction
(Percent)
High Intensity Use
95th
95th
Single
Adult
3.6
(120)
(1249.04)
(94)
Youth A
3.3
Youth B
3.6
Moderate Intensity Use
50th
50th
Single
Adult
0.44
(15)
(126.86)
(94)
Youth A
0.42
Youth B
0.45
Low Intensity Use
10th
10th
Single
Adult
5.9E-02
(2)
(21.86)
(94)
Youth A
5.5E-02
Youth B
6.1E-02
Table 2-41 shows the dermal exposure dose found for the low, moderate, and high intensity use
categories for this condition of use. The ADD of 1-BP for adults varies from 5.9E-02 mg/kg-day to
3.6 mg/kg-day. The ADD of 1-BP for Youth A varies from 5.5E-02 mg/kg-day to 3.3 mg/kg-day.
The ADD of 1-BP for Youth B varies from 6.1E-02 mg/kg-day to 3.6 mg/kg-day.
Page 146 of 486
-------
2.3.2.2.5 Adhesive Accelerant
This condition of use represents consumer uses of product as a solvent for adhesive accelerant for
arts, crafts, and hobby activities. The products are aerosol sprays used to accelerate the time it
takes for adhesives to dry. These products are available to consumers with 1-BP concentrations of
99 percent by weight based on a review of product specific SDS. The room of use is the utility
room, based on the results from the Westat Survey (EPA. 1987) product category cross-walked
with this condition of use. The duration of product use per event for these products ranges from 0.3
minute to 60 minutes based on the Westat Survey (EPA. 1987). However, due to a limitation on the
minimum value available for duration of use within the CEM, the low-end value used for modeling
this condition of use is 0.5 minutes.
Table 2-42. Adhesive Accelerant (Inhalation Exposure Concentration)
Source Description
Parameters Varied
Exposed Receptor
24-hour TWA
Duration
Mass Used
Weight Fraction
(ppm)
(min)
(grams)
(percent)
High Intensity Use
95th
95th
Single
User
18
(60)
(172.45)
(99)
Bystander
4.5
Moderate Intensity Use
50th
50th
Single
User
1.1
(4.25)
(9.98)
(99)
Bystander
0.2
Low Intensity Use
10th
10th
Single
User
0.12
(0.5)
(1.2)
(99)
Bystander
2.5E-02
Table 2-42 shows the inhalation exposure concentrations found for the low, moderate, and high
intensity use categories for this condition of use. The 24-hour TWA air concentrations of 1-BP for
the user varies from 0.12 ppm to 18 ppm. The 24-hour TWA air concentrations of 1-BP for the
bystander varies from 2.5E-02 ppm to 4.5 ppm.
Dermal exposure was evaluated for this condition of use utilizing the CEM (Fraction Absorbed)
model due to the expectation of uninhibited evaporation and no full immersion of body parts into
the product during use. EPA used 10% of one hand as the area and body part exposed.
Table 2-43. Adhesive Accelerant (Dermal Exposure Doses)
Source Description
Parameter Varied
Exposed Receptor
ADD
Duration
Mass Used
Weight
(mg/kg-day)
(min)
(grams)
Fraction
(Percent)
High Intensity Use
95th
95th
Single
Adult
4.8E-02
(60)
(172.45)
(99)
Youth A
4.5E-02
Youth B
4.9E-02
Moderate Intensity Use
50th
50th
Single
Adult
4.8E-02
(4.25)
(9.98)
(99)
Youth A
4.5E-02
Youth B
4.9E-02
Low Intensity Use
10th
10th
Single
Adult
4.8E-02
(0.5)
(1.2)
(99)
Youth A
4.5E-02
Youth B
4.9E-02
Page 147 of 486
-------
Table 2-43 shows the dermal exposure dose found for the low, moderate, and high intensity use
categories for this condition of use. The ADD of 1-BP for adults across all intensities of use (high,
moderate, low) is 4.8E-02 mg/kg-day. The ADD of 1-BP for Youth A across all intensities of use
is 4.5E-02 mg/kg-day. The ADD of 1-BP for Youth B across all intensities of use is 4.9E-02
mg/kg-day. The ADD for each age group across all use conditions is 0.05 mg/kg-day. The identical
ADD is due to the availability of only a single weight fraction for products in this condition of use
and the use of a published experimental absorption fraction value (independent of duration) rather
than an estimated value (reliant on duration).
2.3.2.2.6 Mold Cleaning and Release Product
This condition of use represents consumer uses of product as solvents for mold cleaning and
release. The products are used as anti-adhesive agents intended to prevent bonding between other
substances by discouraging surface attachments. The products are available to consumers with 1-
BP concentrations ranging from 32 percent to 91.5 percent by weight based on a review of product
specific SDS. The room of use is the utility room, based on the results from the Westat Survey
(EPA. 1987) product category cross-walked with this condition of use. The duration of product use
per event for these products ranges from 0.1 minute to 30 minutes based on the Westat Survey
(EPA. 1987). However, due to a limitation on the minimum value available for duration of use
within the CEM, the low-end value used for modeling this condition of use is 0.5 minutes.
Table 2-44. Mold Cleaning and Release Product (Inhalation Exposure Concentration)
Parameters Varied
24-hour TWA
(ppm)
Source Description
Duration
(min)
Mass Used
(grams)
Weight Fraction
(percent)
Exposed Receptor
High Intensity Use
95th
95th
Maximum
User
21
(60)
(192.21)
(91.5)
Bystander
4.2
Moderate Intensity Use
50th
50th
Mean
User
1.4
(2)
(21.14)
(60)
Bystander
0.27
Low Intensity Use
10th
10th
Minimum
User
0.12
(0.5)
(3.84)
(32)
Bystander
2.6E-02
Table 2-44 shows the inhalation exposure concentrations found for the low, moderate, and high
intensity use categories for this condition of use. The 24-hour TWA air concentrations of 1-BP for
the user varies from 0.12 ppm to 21 ppm. The 24-hour TWA air concentrations of 1-BP for the
bystander varies from 2.6E-02 ppm to 4.2 ppm.
Dermal exposure was evaluated for this condition of use utilizing the CEM (Fraction Absorbed)
model due to the expectation of uninhibited evaporation and no full immersion of body parts into
the product during use. EPA used 10% of one hand as the area and body part exposed.
Page 148 of 486
-------
Table 2-45. Mold Cleaning and Release Product (Dermal Exposure Doses)
Source Description
Parameter Varied
Exposed Receptor
ADD
Duration
Mass Used
Weight
(mg/kg-day)
(min)
(grams)
Fraction
(Percent)
High Intensity Use
95th
95th
Maximum
Adult
4.3E-02
(60)
(192.21)
(91.5)
Youth A
4.0E-02
Youth B
4.4E-02
Moderate Intensity Use
50th
50th
Mean
Adult
2.8E-02
(2)
(21.14)
(60)
Youth A
2.6E-02
Youth B
2.9E-02
Low Intensity Use
10th
10th
Minimum
Adult
1.5E-02
(0.5)
(3.84)
(32)
Youth A
1.4E-02
Youth B
1.5E-02
Table 2-45 shows the dermal exposure dose found for the low, moderate, and high intensity use
categories for this condition of use. The ADD of 1-BP for adults ranges from 1.5E-02 mg/kg-day
to 4.3E-02 mg/kg-day. The ADD of 1-BP for Youth A ranges from 1.4E-02 mg/kg-day to 4.0E-02
mg/kg-day. The ADD of 1-BP for Youth B across all intensities of use is 1.5E-02 mg/kg-day to
4.4E-02 mg/kg-day.
2.3.2.3 Multi-Chamber Concentration and Exposure Model (MCCEM)
Overview
The MCCEM predicts indoor air concentrations of, and inhalation exposure to, chemicals released
from products used or materials installed in a residence through a deterministic, mass-balance
approach. It is a peer reviewed EPA model which relies on user provided input parameters, various
assumptions, and several default inputs to generate exposure estimates. The defaults within
MCCEM are a combination of high-end and mean/central tendency values from published
literature, other studies, and values taken from U.S. EPA's Exposure Factors Handbook (U.S. EPA.
2011). The MCCEM has built in flexibility which allows the modeler to modify certain default
values when chemical specific information is available. The MCCEM provides a time series air
concentration profile (intermediate concentration values produced prior to applying pre-defined
activity patterns) for each run. Readers can learn more about the model by reviewing the MCCEM
user guide (U.S. EPA. 2019d).
Approach and Inputs
There are four types of source models for inhalation exposure available within the MCCEM,
including: constant source, single-exponential source, incremental source, and a special cases or
expressions source not otherwise addressed by the first three source models (referred to in the
MCCEM as data entry form). Both conditions of use identified in Table 2-31 (coin and scissors
cleaner and automobile AC flush) for which inhalation exposure was assessed with the MCCEM
utilized the constant source model. Since the MCCEM does not have a dermal component, dermal
exposure from these two conditions of use was evaluated with CEM as shown in Table 2-31 [Coin
Page 149 of 486
-------
and Scissors Cleaner CEM (Permeability) model (P_DER2b) and Automobile AC Flush CEM
(Fraction Absorbed) model (P_DER2a).
Constant Source Model (MCCEM): This model assumes the emission source emits at a constant
rate for the entire period during which it is active. This model requires the user to specify the
constant emission rate for the emission source as one of the inputs.
P DER2a (Dermal Dose from Product Applied to Skin, Fraction Absorbed Model): This model
uses an absorption coefficient to estimate dermal exposure based on the absorbed dose of a
chemical from a thin film applied onto the skin. This methodology assumes the application of the
chemical of concern (or product containing the chemical of concern) once to a specific film
thickness. Utilizing an assumption that the entire mass of the chemical in the thin film enters the
skin, this model then estimates the absorbed dose by applying the absorption coefficient to the
entire mass of chemical within the skin. This model essentially measures two competing processes,
evaporation of the chemical from the skin and penetration of the chemical deeper into the skin, and
therefore is more applicable to conditions of use where evaporation is uninhibited and full
immersion of body parts does not occur during use.
P DER2b (Dermal Dose from Product Applied to Skin, Permeability Model) (CEM): This model
uses a skin permeability coefficient to estimate dermal exposure based on potential or absorbed
doses for products that come in direct contact with the skin. The permeability coefficient can be a
user defined value (if available for the chemical of concern) or estimated using the built in
permeability estimator within CEM. This model is based on the ability of a chemical to penetrate
the skin layer once contact occurs. This model assumes a constant supply of chemical, directly in
contact with the skin, throughout the exposure duration. This model does not consider evaporative
losses in its estimates of dermal exposure and therefore is more representative of a dermal
exposure condition where evaporation is limited or prohibited due to direct immersion of skin into
a product or use of a product soaked rag or other barrier that is in direct contact with unprotected
skin during product use.
EPA obtained time-varying indoor concentrations across the entire time period simulated in each
model run (72 hours for both MCCEM and CEM). EPA also utilized the near-field/far-field option
within MCCEM. Use of these two options together provided EPA with zone specific
concentrations (Zone 1 near-field, Zone 1 far-field, and Zone 2) to which a stay-at-home activity
pattern was applied for the users and bystanders during post-processing within Microsoft Excel.
Post-processing involved calculating a rolling 24-hour time weighted average (TWA)
concentration for each personal exposure time series (user and bystander). The maximum 24-hour
TWA was then identified and extracted as the exposure concentration.
Identification of the inhalation exposure scenario to be evaluated for the coin and scissors cleaner
and automobile AC flush conditions of use began with a general internet search and investigation
into these uses. The search and investigation found the coin cleaning process typically involved
placing the coin cleaner product into a small, open top dish or bowl. Coins to be cleaned are then
placed within the pool of product, soaked, scrubbed/wiped, and then removed for drying. The
automobile AC flush process involved directly spraying the flush product into the opened
Page 150 of 486
-------
automobile AC system. The product is transferred through the system by pressure to the opposite
end and expelled into an open top bucket where it is collected. Both of these processes involve an
open top container, of certain dimensions, which contains a pool of the product being evaluated.
Inhalation exposure then occurs as a result of 1-BP evaporation from a pool of liquid product in
each container.
Dermal exposure for the coin and scissors cleaner condition of use is possible as a result of
immersion of the users hand into the product being evaluated. Dermal exposure for the automobile
AC flush condition of use is possible during connection of the product container to the automobile
AC system (at head and shoulder level), spraying from an incorrect connection, splashing from the
material expelling from the automobile AC system, and splashing during transport/clean-up of the
product from the open top container.
Numerous input parameters are required to generate exposure estimates within the MCCEM. These
parameters help define various aspects of the model run, exposure scenario, activity patterns, and
receptor specific information. Inputs include run time, house/residence information (e.g., number
of zones, building volumes, air flows), emissions information (emission rate, zone of emissions
source location, start/end time, and source model), activity pattern information, dose information,
and receptor information (e.g., inhalation rate, body weight).
The inputs needed for the MCCEM include: (1) the emission rate; (2) product amount and duration
of use; (3) house and zone volumes; and (4) airflows to and from each zone. Each of these input
categories are discussed below. Detailed tables of all input parameters for each use evaluated with
the MCCEM are provided in the 1-BP Supplemental File: Information on Consumer Exposure
Assessment Model Input Parameters (EPA. 2019a).
Emission Rate
The emission rate of 1-BP from the pool of liquid product for the two conditions of use evaluated
using the MCCEM was estimated outside of the MCCEM. A study by Guo (Quo, 2002), compiled
and briefly discussed fifty-two indoor emission source models. Two of the models compiled (M32
and M33) can be applied to estimate an emission rate from a pool of liquid.
The M32 model (Javiock. 1994). applies to an evaporating solvent pool with a fixed surface area.
At a given temperature, the emission rate calculated using the M32 model is determined by (1) the
gas-phase mass transfer coefficient, (2) the vapor pressure, and (3) the back pressure effect. The
M33 model (Chang and Krebs. 1992). was developed for sublimation of p-dichlorobenzene from
moth cakes. However, sublimation and evaporation of pure compounds share similar mechanisms
and therefore the M33 model can also be applied to emissions from solvent pools (Guo. 2002).
The M33 model (Chang and Krebs. 1992) was utilized to estimate the emission rate for both the
coin and scissors cleaner and automobile AC flush conditions of use. This model is represented as
follows:
E = kg (Cv - C)
Where:
Page 151 of 486
-------
E= the emission rate (mg/m2/hr)
Kg= the gas-phase mass transfer coefficient (m/hr)
Cv= the saturation concentration for a pure compound (mg/m3)
C= the prevailing indoor air concentration (mg/m3)
EPA assumed zero for the prevailing indoor air concentration when determining the emission rate
for these two scenarios. This assumption therefore makes the emission rate in the M33 model
product of three quantities: (1) mass-transfer coefficient; (2) saturation concentration; and (3)
exposed surface area. The exposed surface area of the two reservoirs is needed to both estimate the
characteristic length of the reservoir (needed to determine the gas phase mass transfer coefficient)
as well as converting the emission rate from the M33 model (mg/m2/hr) into the correct units
needed for the MCCEM (mg/hr).
To estimate the mass-transfer coefficient, EPA used the program PARAMS
(https://www.epa.gov/air-research/parameters-params-program-version-ll-indoor-emission-
source-modeling). which involves the following components:
• Air Density, calculated at 23 C and 50% RH;
• Viscosity of Air, calculated at 23 C;
• Velocity, the midpoint of the recommended range of 5-10 cm/s;
• Diffusivity in air, calculated using the Wilke Lee (WL) method (see input screen below); and
• Characteristic length - PARAMS describes this parameter as follows:
"Characteristic length is often approximated by the square root of the source area."
The saturation concentration for 1-BP is 731,535 mg/m3 (732 g/m3). For the coin cleaner
reservoir, EPA chose a small bowl with a 4-inch diameter, giving a source area of 81 cm2, a
characteristic length of 9 cm, and an estimated mass-transfer coefficient of 6.01 m/hr. For the
automobile AC flush reservoir, EPA chose a bucket with a 12-inch diameter, giving a source area
of 730 cm2, a characteristic length of 27.0 cm, and an estimated mass-transfer coefficient of 3.47
m/h.
The emission rate for the coin cleaner utilized as the input for the MCCEM was obtained by
multiplying the estimated mass transfer coefficient (6.01 m/hr) by the saturation concentration for
1-BP (731,535 mg/m3), and the source area (0.0081 m2). This gives an estimated emission rate for
1-BP from the coin cleaner reservoir of 35,612 mg/hr (36 g/hr). Similarly, the emission rate for the
automobile AC flush utilized as the input for the MCCEM was obtained by multiplying the
estimated mass transfer coefficient (3.47 m/hr) by the saturation concentration of 1-BP (731,535
mg/m3), and the source area (0.073 m2). This gives an estimated emission rate for 1-BP from the
automobile AC flush reservoir of 185,305 mg/hr (185 g/hr).
Page 152 of 486
-------
Product Amount and Duration of Use
To characterize a potential range of consumer user and bystander exposures, modeling efforts
involved identifying appropriate parameters to vary across a range of values representative of the
expected conditions of use evaluated. Unlike the scenarios modeled with the CEM, involving an
immediate uptake of the overspray fraction and exponential decay rate for the material contacting
the surface, the two scenarios modeled with the MCCEM assumed only a constant rate of material
evaporating from the surface of the liquid pool which is in effect until all available 1-BP mass is
evaporated. This approach results in the emission rate being governed by the surface area of the
liquid pool and not dependent on chemical mass, provided the duration of use is less than the time
it takes for all 1-BP mass to evaporate. For both the coin and scissors cleaner and automobile AC
flush conditions of use, the time it takes for all 1-BP mass to evaporate from the products is longer
than the durations of use by the consumer evaluated for this analysis. Since emission rate is not
dependent on chemical mass for the two MCCEM scenarios, the only parameter varied for the coin
and scissors cleaner and automobile AC flush conditions of use was duration of use. This results in
three exposure scenarios per condition of use.
EPA chose three durations of use for inhalation exposure (15, 30, and 60 minutes) for the coin and
scissors cleaner condition of use. Coin cleaning is expected to be a somewhat passive activity
where coins may remain undisturbed within the pool for an extended period of time. As a result,
EPA expects dermal exposure will occur for a shorter period of time consisting of when coins are
placed into the product, potentially scrubbed/wiped within the product, and taken out for drying.
Outside of these activities, dermal exposure is not expected to occur although the user will remain
within the room inhaling the vapors expelled from the pool. For dermal exposure EPA chose three
durations (2, 4, and 6 minutes) which represent the total duration of dermal exposure during use.
EPA chose three durations of use for inhalation exposure (5, 15, and 30 minutes) for the
automobile AC flush condition of use. Unlike coin cleaning, automobile AC flushing is an active
process where material is constantly sprayed into the system, flushed through, and exits the system.
Inhalation exposure occurs for the entire period of time and since it is an active process, dermal
exposure can also occur for the entire period of time. As a result, for dermal exposure EPA also
presents the exposure values representing 5, 15, and 30 minutes of ongoing dermal exposure.
House and Zone Volumes and Airflows
The zone volumes and airflow rates for the coin and scissors cleaner and automobile AC flush
condition of use are discussed below and summarized in two tables in Appendix D. For the coin
and scissors cleaner condition of use, EPA is assuming the room of use to be the utility room, with
a volume of 20 m3 that is further split into near-field and far-field zones for which the respective
volumes (1 m3 and 19-m3) are consistent with CEM defaults. The assumed house volume is 446
m3, resulting in a volume of 426 m3 for the third zone, termed the "rest of house" or ROH.
The air exchange rate for the house (0.45) is the same as the CEM default. EPA used an interzonal
airflow rate of 100 m3/h between the near field and far-field. EPA assumed that there was no air
Page 153 of 486
-------
flow between the near field and outdoors (Zone 0). For the interzonal airflow rate between the
utility room and ROH, the CEM default rate of 107.1 m3/h was used.
For the auto AC flush scenario, EPA assumed the room of use to be the garage with a volume of
118 m3. This volume is the average for 15 single-family homes with attached garages as reported
by Batterman et al. (Batterman et al.. 2007). The garage was further split into a 4-m3 near field and
a 114-m3 far field. Zone 3 was defined as the entire house volume of 446 m3, which did not include
the garage.
The air exchange rate for the house (0.45) is the same as the CEM default. Relatively few
measurements have been taken of garage air exchange rates. Emmerich et al. (Emmerich et al..
2003) used a blower door to measure the airtightness of garages under induced-pressurization
conditions for a limited sample of homes but with a range of house ages, styles, and sizes. The
average airtightness measured was 48 air changes per hour at 50 Pa (ACH50), which corresponds
to an air exchange rate of- 2.5 air exchanges/h (giving an airflow rate of 295 m3/h ) under naturally
occurring conditions. EPA also assumed an airflow rate of 107.1 m3/h between the garage and
house as well as an airflow rate of zero between the near field and outdoors.
Results
Modeling results for inhalation exposures evaluated with the MCCEM are summarized and
discussed below. Modeling results for dermal exposures for the coin and scissors cleaner and
automobile AC flush conditions of use with the CEM are also summarized and discussed below.
Results are presented by condition of use. All results for all iterations modeled are provided in the
1-BP Supplemental File: Information on Consumer Exposure Assessment Model Outputs (EPA.
2019b).
Results are presented in this section for all three iterations run with the MCCEM for the coin and
scissors cleaner and automobile AC flush condition of use. Inhalation concentrations are presented
in parts per million (ppm) while dermal doses are presented as average daily doses (ADD) in
milligrams of 1-BP per kilogram body weight per day (mg/kg-day). The three iterations presented
provide a range of exposure concentrations across each condition of use modeled. The three
descriptors utilized for the MCCEM iterations are the same as those used for the CEM results.
However, since only one parameter was varied for the two conditions of use evaluated with the
MCCEM, the descriptors are only based on the duration of use per event.
Hish Intensity Use: Refers to the model iteration which utilizes the highest duration of use per
event.
Moderate Intensity Use: Refers to the model iteration which utilizes the median duration of use per
event.
Low Intensity Use: Refers to the model iteration which utilizes the lowest duration of use per event.
Page 154 of 486
-------
2.3.2.3.1 Coin and Scissors Cleaner
This condition of use represents consumer uses of product as a solvent for cleaning in the form of
liquid cleaner. The products are used to dissolve oils, greases, stains, or to cleanse, sanitize, scour,
polish, protect or improve the appearance of surfaces. These products are available to consumers
with a 1-BP concentration of 50 to 100 percent by weight based on a review of product specific
SDS. The room of use is assumed to be the utility room. The duration of use per event evaluated
for these products ranged from 15 minutes to 60 minutes.
Inhalation Exposure
Table 2-46. Coin and Scissors Cleaner (Inhalation Exposure Concentration)
Source Description
Parameters Varied
Exposed Receptor
24-hour TWA
Duration
Mass Used
Weight Fraction
(ppm)
(min)
(grams)
(percent)
High Intensity Use
High
Maximum
Maximum
User
2.0
(60)
(624.5)
(100)
Bystander
1.0
Moderate Intensity Use
Median
Mean
Mean
User
1.5
(30)
(312.3)
(75)
Bystander
0.47
Low Intensity Use
Low
Minimum
Minimum
User
1.2
(15)
(126.9)
(50)
Bystander
0.22
Table 2-46 shows the inhalation exposure concentrations found for the low, moderate, and high
intensity use categories for this condition of use. The 24-hour TWA air concentrations of 1-BP for
the user varies from 1.2 ppm to 2.0 ppm. The 24-hour TWA air concentrations of 1-BP for the
bystander varies from 0.22 ppm to 1.0 ppm.
Dermal Exposure
Dermal exposure was evaluated for this condition of use utilizing the CEM (Permeability) model
due to the possibility of a continuous supply of product on the skin and expected inhibited or
prohibited evaporation resulting from wiping with a product soaked rag during use. EPA used 10%
of one hand as the area and body part exposed.
Table 2-47. Coin and Scissors Cleaner (Dermal Exposure Doses)
Source Description
Parameter Varied
Exposed Receptor
ADD
(mg/kg-day)
Duration
(min)
Mass Used
(grams)
Weight
Fraction
(Percent)
High Intensity Use
High
(6)
Maximum
(624.5)
Maximum
(100)
Adult
7.6E-02
Youth A
7.1E-02
Youth B
7.7E-02
Moderate Intensity Use
Median
(4)
Median
(312.3)
Median
(75)
Adult
3.8E-02
Youth A
3.5E-02
Youth B
3.9E-02
Low Intensity Use
Low
(2)
Minimum
(126.9)
Minimum
(50)
Adult
1.3E-02
Youth A
1.2E-02
Youth B
1.3E-02
Page 155 of 486
-------
Table 2-47 shows the dermal exposure dose found for the low, moderate, and high intensity use
categories for this condition of use. The ADD of 1-BP for adults varies from 1.3E-02 mg/kg-day to
7.6E-02 mg/kg-day. The ADD of 1-BP for Youth A varies from 1.2E-02 mg/kg-day to 7.7E-02
mg/kg-day. The ADD of 1-BP for Youth B varies from 1.3E-02 mg/kg-day to 7.7E-02 mg/kg-day.
2.3.2.3.2 Automobile AC Flush
This condition of use represents consumer uses of product as an automotive care product in the
form of a liquid cleaner. The product is used to dissolve and flush out foreign materials from the
coils of an automobile AC coil. These products are available to consumers with 1-BP
concentrations greater than 90 percent by weight based on a review of product specific SDS. The
room of use is assumed to be the garage. The duration of product use per event evaluated for this
product ranges from 5 minutes to 30 minutes.
Inhalation Exposure
Table 2-48. Automobile AC Flush (Inhalation Exposure Concentration)
Source Description
Parameters Varied
Exposed Receptor
24-hour TWA
Duration
Mass Used
Weight Fraction
(ppm)
(min)
(grams)
(percent)
High Intensity Use
High
Maximum
Single
User
0.80
(30)
(573)
(90)
Bystander
0.51
Moderate Intensity Use
Median
Mean
Single
User
0.53
(15)
(286)
(90)
Bystander
0.24
Low Intensity Use
Low
Minimum
Single
User
0.37
(5)
(143)
(90)
Bystander
7.5E-02
Table 2-48 shows the inhalation exposure concentrations found for the low, moderate, and high
intensity use categories for this condition of use. The 24-hour TWA air concentrations of 1-BP for
the user varies from 0.37 ppm to 0.80 ppm. The 24-hour TWA air concentrations of 1-BP for the
bystander varies from 7.5E-02 ppm to 0.51 ppm.
Dermal Exposure
Dermal exposure was evaluated for this condition of use utilizing the CEM (Fraction Absorbed)
model due to the expectation of uninhibited evaporation and no full immersion of body parts into
the product during use. EPA used the full area of face, hands, and arms as the area and body parts
exposed.
Table 2-49. Automobile AC Flush (Dermal Exposure Doses)
Source Description
Parameter Varied
Exposed Receptor
ADD
(mg/kg-day)
Duration
(min)
Mass Used
(grams)
Weight
Fraction
(Percent)
High Intensity Use
High
(30)
Maximum
(573)
Single
(90)
Adult
0.50
Youth A
0.47
Youth B
0.52
Page 156 of 486
-------
Moderate Intensity Use
Median
Median
Single
Adult
0.50
(15)
(286)
(90)
Youth A
0.47
Youth B
0.52
Low Intensity Use
Low
Minimum
Single
Adult
0.50
(5)
(143)
(90)
Youth A
0.47
Youth B
0.52
Table 2-49 shows the dermal exposure dose found for the low, moderate, and high intensity use
categories for this condition of use. The ADD of 1-BP for adults across all intensities of use (high,
moderate, low) is 0.50 mg/kg-day. The ADD of 1-BP for Youth A across all intensities of use is
0.47 mg/kg-day. The ADD of 1-BP for Youth B across all intensities of use is 0.52 mg/kg-day. The
identical ADD is due to the availability of only a single weight fraction for products in this
condition of use and the use of a published experimental absorption fraction value (independent of
duration) rather than an estimated value (reliant on duration).
2.3.2.4 Indoor Environmental Concentrations in Buildings with Conditioned
and Unconditioned Zones Model (IECCU)
Overview
The IECCU predicts indoor air concentrations of chemicals released from products used or
materials installed in a building through a deterministic, mass-balance approach. It is a peer
reviewed EPA model which relies on user provided input parameters and various assumptions to
generate exposure estimates. The IECCU can be used as (1) a general-purpose indoor exposure
model in buildings with multiple zones, multiple chemicals, and multiple sources and sinks or (2) a
special purpose concentration model for simulating the effects of sources in unconditioned zones
on the indoor environmental concentrations in conditioned zones. Readers can learn more about the
IECCU by reviewing the IECCU user guide (U.S. EPA. 2019c).
Approach and Inputs
The IECCU was utilized in this evaluation as a general purpose indoor exposure model to estimate
time-series indoor air concentrations within a residence where THERMAX™ insulation boards are
installed. THERMAX™ insulation board is a non-structural, rigid board insulation consisting of a
glass-fiber-infused polyisocyanurate foam core laminated between 1.0 mm smooth, reflective
aluminum facers on both sides. While rigid insulation would typically be installed in walls and
encapsulated under drywall or other material, a general internet search identified the availability of
certain pre-finished products which can be installed without the need to "finish" it with drywall
provided applicable building or other codes allow. Based on a review of available products and
public comments included in the Docket for this evaluation, THERMAX™ insulation boards are
the only U.S. made rigid insulation board which includes 1-BP within its formulation.
The evaluation of the insulation (off-gassing) condition of use was expanded in this risk evaluation
to include two building configurations as well as chronic exposure. The first building configuration
consisted of an attic/living space/crawl space configuration where the insulation board was installed
in the attic (roof and floor) and crawlspace (ceiling). The second building configuration consisted
of an attic/living space/full basement configuration where the insulation board was installed in the
attic (roof and floor) and basement (walls). Once the rigid insulation board is installed, there is an
Page 157 of 486
-------
initial spike in 1-BP concentration due to off-gassing. Following the initial spike, 1-BP
concentrations due to off-gassing quickly fall to lower, more stable but decreasing levels which
may be maintained for months or even years, potentially resulting in a longer term exposure to
lower concentrations. This long-term, lower concentration exposures lend itself to the possibility of
a longer-term chronic exposure. While spray foam insulation is a consumer product, EPA did not
identify any consumer spray foam products which identified 1-BP as a component of its
formulation. As a result, this risk evaluation only considered 1-BP exposure from the
THERMAX™ rigid insulation board product.
Other changes to the approach for the insulation (off-gassing) condition of use incorporated into
this evaluation include a smaller surface area from which 1-BP may off-gas. This change was made
because it is expected the aluminum facing applied to the front and back surfaces of the full
insulation board is impermeable to 1-BP, therefore the area from which 1-BP may off-gas was
limited for this evaluation to all four edges of each insulation board installed. Additionally, since
the amount of a chemical of concern off-gassing is sensitive to temperature (especially in
unconditioned zones like the attic and crawlspace, and possibly to some degree a full basement),
this evaluation modeled short-term concentrations based on four installation times (February 1st,
May 1st, August 1st, and November 1st). These values address initial spikes in concentration
immediately following installation and seasonal variation of concentrations resulting from the
effects of temperature. A representative concentration for exposure estimation purposes was then
calculated by averaging the results from all four installation dates for each zone.
The general mass balance equation used by the IECCU to determine the change in the
concentration of a chemical of concern in air within a given zone is determined by six factors: (1)
the emissions from the sources in the zone, (2) the rate of chemical removal from the zone by the
ventilation and interzonal air flows, (3) the rate of chemical carried into the zone by the infiltration
and interzonal air flows, (4) the rate of chemical sorption by interior surfaces, (5) the rate of
chemical sorption by airborne particles, and (6) the rate of chemical sorption by settled dust. Since
1-BP is highly volatile, once it is in the vapor phase, 1-BP is expected to remain in the vapor phase.
As a result, EPA only considered the first three factors listed above when evaluating inhalation
exposure to 1-BP for the insulation off-gassing condition of use. Dermal exposure is not expected
from off-gassing and therefore was not evaluated.
Input parameters for running the IECCU were obtained from published literature, including U.S.
EPA's Exposure Factors Handbook (U.S. EPA. 2011). or estimated with either empirical or QSAR
models. A discussion of some specific inputs are included below and summarized in Table 2-50
and Table 2-51. Detailed tables of all input parameters for the IECCU are provided in the 1-BP
Supplemental File: Information on Consumer Exposure Assessment Model Input Parameters
(EPA. 2019a).
A three-zone configuration described by Bevington et al. in (Sebroski. 2017) was used to represent
a generic residential building for both building configurations. The assumed location of installed
insulation for the attic/living space/crawl space building configuration was the floor and rafters
within the attic and the ceiling of the crawlspace area which spans the entire blue print of the
Page 158 of 486
-------
building floor area. The assumed location of installed insulation for the attic/living space/full
basement building configuration was the floor and rafters within the attic and all four walls in the
basement. The baseline ventilation and interzonal air flows for the two building configurations are
shown in Figure 2-13 and Figure 2-14.
Zone 2 (Attic)
\\ = 150 m3
Ql0=15O in*1/for
Zone 1 (Living Space)
V, = 300 mJ
Zone 3 (Crawlspace)
V, = 150 m3
Return Air
HVAC
Figure 2-13. The Three-Zone Configuration for a Residential Setting and Baseline
Ventilation and Interzonal Air Flows for the Attic/Living Space/Crawlspace Building
Configuration.
Page 159 of 486
-------
HVAC
Zone 3 (Basement)
V3 = 180 m3
Rel
Zone 1 (Living Space)
Vj = 300 mJ
Figure 2-14. The Three-Zone Configuration for a Residential Setting and Baseline
Ventilation and Interzonal Air Flows for the Attic/Living Space/Full Basement Building
Configuration.
Table 2-50 summarizes general inputs utilized in the IECCU modeling runs for the two building
configurations. Insulated area is based on the available surface area where insulation was installed.
This includes an assumption that a Vi inch gap exist between adjacent panels and the ceiling and
floor. Number of panels is based on the area needing insulation and a product size of four feet wide
by eight feet long by two inches thick. Source area is calculated by multiplying the number of
panels needed for each area by the total area of all four edges of the insulation board shown in
Table 2-51. Since EPA assumes insulation is only installed in the attic and crawlspace/attic and
basement, there is no insulated area in the living space.
Table 2-50. Zone Names, Volumes, and Baseline Ventilation Rates
Zone name
Zone volume
(m3)
Insulated Area
(m2)
Number of Panels
needed
Source Area
Ventilation
Rate (h1)
Living space
300
N/A
N/A
N/A
0.5
Attic
150
180
60
22.3
2.0
Crawlspace
150
120
40
14.9
1.0
Basement
180
75
30
11.2
0.45
Table 2-51. Parameters for the 1-BP Sources
Property
Value
Total Area four board edges (m2)
0.372
Page 160 of 486
-------
Board thickness (cm)
5.1
1-BP content
0.5%
Density (g/cm3)
0.03
Partition coef. (K) at 21 °C
3.3
a = 0.9
K as a function of temp.
1//, S. 14 10;
Diffusion coef. (D) at 20 °C
1.88E-11
Results
Sensitivity Analysis'. A sensitivity analysis was conducted to see the impact of installation date and
temperature on the off-gassing of 1-BP from rigid insulation board. These results are presented in
Figure 2-15 and Figure 2-16 for the attic/living space/crawl space and attic/living space/basement
building configurations, respectively.
25.0
20.0
15.0
10.0
5.0
0.0
~ Living space
~ Attic
~ Crawlspace
10.1
11.3
5.16
2.38
0.59
1.68
JZL
21.2
3.05
17.5
8.1
5.54
1.07
February 1st May 1st August 1st November 1st
Installation Date
Figure 2-15. 24-Hour TWA Concentrations for Attic/Living Space/Crawlspace Building
Configuration Across Four Different Installation Dates
Page 161 of 486
-------
25.0
20.0
M 15.0
10.0
5.0
0.0
~ Living space
~ Attic
~ Basement
10.50
10.2
10.8
4.01
2.54
4.54
21.4
5.32
11.2
February 1st May 1st August 1st
Installation Date
10.6
5.70
4.23
November 1st
Figure 2-16. 24-Hour TWA Concentrations for Attic/Living Space/Full Basement Building
Configuration Across Four Different Installation Dates
Figure 2-15 and Figure 2-16 show the variation in concentrations based on the date when initial
installation of the rigid insulation board occurs. These figures demonstrate that off-gassing is
sensitive to temperature and the highest estimated concentrations occur in August. The seasonal
fluctuation is particularly sensitive in unconditioned zones like the attic or crawlspace.
Concentrations in the basement are also impacted.
Inhalation Exposure: Modeling results for acute and chronic inhalation exposures evaluated with
the IECCU are summarized and discussed below. Results are presented for both building
configurations.
2.3.2.4.1 Insulation (Off-Gassing): Acute Inhalation Exposure
This condition of use represents consumer use of insulation material as building and construction
materials in the form of rigid board insulation for interior applications. The product evaluated is
assumed to contain 0.5 percent by weight of 1-BP. The rooms of use where the product is installed
are assumed to include the attic and either the crawlspace or the basement of a residential home.
The acute inhalation exposure evaluation considers short-term exposure to 1-BP resulting from an
initial spike in the air concentration of 1-BP from newly installed rigid insulation board. It
incorporates a higher initial air concentration for a short duration.
To obtain representative short-term inhalation exposure concentrations, EPA calculated the
average 24-hour TWA concentration across all four installation dates utilized for the sensitivity
analysis for each zone in both building configurations. Table 2-52 summarizes the calculated
average 24-hour TWA concentrations for each zone. The IECCU provides concentrations in
micrograms per cubic meter ([j,g/m3). These were converted to ppm with the following equation:
Cppm = ((Cm /ms/lOOO) X 24.45)/MW
Page 162 of 486
-------
Where:
Cppm is concentration of 1-BP in units of ppm
Qtg/m3 is concentration of 1-BP in units of micrograms per cubic meter
24.45 is a conversion factor representing molar volume (L)
MW is the molecular weight of 1-BP (122.99 g/mol)
Table 2-52. Average 24-Hour TWA Concentration of 1-BP by Zone in Two Building
Configurations
Avg. 24-Hour TWA (jig/m3)
Avg. 24-Hour TWA (ppm)
Attic
Living
Space
Crawlspace/
Basement
Attic
Living
Space
Crawlspace/
Basement
Attic/Living
Space/Crawlspace
9.8
1.6
11
2.0E-03
3.2E-04
2.1E-03
Attic/Living
Space/Basement
10
4.5
11
2.0E-03
9.0E-04
2.1E-03
Table 2-52 shows the inhalation exposure concentrations found for the attic/living
space/crawlspace and the attic/living space/basement building configuration. The 24-hour TWA air
concentration of 1-BP in the attic of both building configurations is 2.0E-03 ppm. The 24-hour
TWA air concentration of 1-BP in the crawlspace and basement is 2.1E-03 ppm. The 24-hour
TWA air concentrations of 1-BP in the living space of each building configuration varies by a
factor of approximately 3 (3.2E-04 ppm for the attic/living space/crawlspace and 9.0E-04 ppm for
the attic/living space/basement building configuration).
2.3.2.4.2 Insulation (Off-Gassing): Chronic Inhalation Exposure
The chronic inhalation exposure evaluation considers longer-term exposure to 1-BP. This
evaluation modeled chronic inhalation exposure concentrations over a seven year period. The
seven year simulation assumed the insulation boards are installed on May 1st. The seven year
period captures the initial spike in the air concentration of 1-BP from newly installed rigid
insulation board, the rapid decrease in the air concentration of 1-BP following initial installation,
and relatively stable but lower air concentrations of 1-BP over an extended period of time.
Table 2-53 and Table 2-54 summarize the calculated annual TWA concentrations for each zone for
each year for the attic/living space/crawlspace and attic/living space/basement building
configurations, respectively. To obtain a representative long-term concentration, EPA calculated a
seven year average for each zone by adding each individual annual concentration together and
dividing by seven.
Page 163 of 486
-------
Table 2-53. Predicted 1-Year TWA Concentrations by Zone for the Attic/Living
Space/Crawlspace Building Configuration
Annual TWA (|ig/m3)
Annual TWA (ppm)
Attic
Living Space
Crawlspace
Attic
Living Space
Crawlspace
Year 1
6.3E-01
1.0E-01
6.0E-01
1.2E-04
2.0E-05
1.2E-04
Year 2
2.7E-01
4.4E-02
2.6E-01
5.3E-05
8.7E-06
5.2E-05
Year 3
2.1E-01
3.4E-02
2.0E-01
4.1e-05
6.7E-06
3.9E-05
Year 4
1.7E-01
2.8E-02
1.7E-01
3.5E-05
5.7E-06
3.3E-05
Year 5
1.5E-01
2.5E-02
1.5E-01
3.0E-05
5.0E-06
2.9E-05
Year 6
1.4E-01
2.3E-02
1.3E-01
2.7E-05
4.5E-06
2.6E-05
Year 7
1.3E-01
2.1E-02
1.2E-01
2.5E-05
4.1E-06
2.5E-05
7-Year Avg.
2.4E-01
4.0E-02
2.3E-01
4.8E-05
7.9E-06
4.6E-05
Table 2-54. Predicted 1-Year TWA Concentrations by Zone for the Attic/Living
Space/Basement Building Configuration
Annual TWA (jig/m3)
Annual TWA (ppm)
Attic
Living Space
Crawlspace
Attic
Living Space
Crawlspace
Year 1
6.4E-01
2.5E-01
5.7E-01
1.3E-04
5.0E-05
1.1E-04
Year 2
2.7E-01
1.1E-02
2.5E-01
5.4E-05
2.2E-05
4.9E-05
Year 3
2.1E-01
8.4E-02
1.9E-01
4.2e-05
1.7E-05
3.8E-05
Year 4
1.8E-01
7.1E-02
1.6E-01
3.5E-05
1.4E-05
3.2E-05
Year 5
1.6E-01
6.2E-02
1.4E-01
3.1E-05
1.2E-05
2.8E-05
Year 6
1.4E-01
5.6E-02
1.3E-01
2.8E-05
1.1E-05
2.5E-05
Year 7
1.3E-01
5.2E-02
1.2E-01
2.6E-05
1.0E-05
2.4E-05
7-Year Avg.
2.5E-01
9.8E-02
2.2E-01
4.9E-05
2.0E-05
4.4E-05
The 7-year average TWA air concentrations of 1-BP in the attic for both building configurations is
approximately the same (4.8E-05 and 4.9E-05 ppm). The 7-year average TWA air concentrations
of 1-BP in the crawlspace and basement for both building configurations is also approximately the
same (4.6E-05 and 4.4E-05 ppm). The 7-year average TWA air concentrations of 1-BP in the
living space of each building configuration varies by a factor of approximately 2.5 (7.9E-06 ppm
for the attic/living space/crawl space and 2.0E-05 ppm for the attic/living space/basement building
configuration).
2.3.2.5 Summary of Consumer Exposure Assessment
Consumer exposure was evaluated for nine consumer conditions of use summarized in Table 2-31
(aerosol spray degreaser/cleaner-general, aerosol spray degreaser/cleaner-electronics, spot cleaner
and stain remover, coin and scissors cleaner, spray cleaner-general, adhesive accelerant,
automobile AC flush, mold cleaning and release product, insulation (off-gassing)). All nine
consumer uses were evaluated for inhalation and dermal exposure, excluding the insulation (off-
gassing) COU which was only evaluated for inhalation exposure.
Page 164 of 486
-------
The results for all conditions of use and exposure routes presented in Sections 2.3.2.2 and 2.3.2.3
are summarized in Table 2-55 (Inhalation) and Table 2-56 (Dermal). The results for the insulation
(off-gassing) condition of use are shown in Table 2-57.
Table 2-55. Inhalation Results Summary
Condition of Use
Scenario Description
24-hour TWA (ppm)
User
Bystander
Model Used
Aerosol Spray
Degreaser/Cleaner-General
High Intensity Use
141
41
CEM
Moderate Intensity Use
19
5.0
Low Intensity Use
1.0
0.25
Aerosol Spray
Degreaser/Cleaner-Electronics
High Intensity Use
30
8.7
CEM
Moderate Intensity Use
1.4
0.35
Low Intensity Use
6.7E-02
1.9E-02
Spot Cleaner and Stain
Remover
High Intensity Use
47
7.2
CEM
Moderate Intensity Use
3.4
0.54
Low Intensity Use
0.26
4.8E-02
Coin and Scissors Cleaner
High Intensity Use
2.0
1.0
MCCEM
Moderate Intensity Use
1.5
0.47
Low Intensity Use
1.2
0.22
Spray Cleaner-General
High Intensity Use
133
33
CEM
Moderate Intensity Use
14
2.7
Low Intensity Use
2.3
0.44
Adhesive Accelerant
High Intensity Use
18
4.5
CEM
Moderate Intensity Use
1.1
0.20
Low Intensity Use
0.12
2.5E-02
Automobile AC Flush
High Intensity Use
0.8
0.51
MCCEM
Moderate Intensity Use
0.53
0.24
Low Intensity Use
0.37
7.5E-02
Mold Cleaning and Release
Product
High Intensity Use
21
4.2
CEM
Moderate Intensity Use
1.4
0.27
Low Intensity Use
0.12
2.6E-02
Table 2-56. Dermal Results Summary
Condition of Use
Scenario Description
Average Daily Dose
(mg/kg-day)
Model Used
Adult
Youth A
Youth B
Aerosol Spray
Degreaser/Cleaner-General
High Intensity Use
3.5
3.3
3.6
CEM
(Permeability)
Moderate Intensity Use
0.23
0.22
0.24
Low Intensity Use
1.7E-02
1.6E-02
1.7E-02
Aerosol Spray
Degreaser/Cleaner-
Electronics
High Intensity Use
4.6E-02
4.3E-02
4.7E-02
CEM (Fraction
Absorbed)
Moderate Intensity Use
3.4E-02
3.2E-02
3.5E-02
Low Intensity Use
2.40E-02
2.20E-02
2.40E-02
High Intensity Use
0.87
0.81
0.89
Page 165 of 486
-------
Spot Cleaner and Stain
Remover
Moderate Intensity Use
9.1E-02
8.5E-02
9.3E-02
CEM
(Permeability)
Low Intensity Use
4.3E-03
4.1E-03
4.4E-03
Coin and Scissors Cleaner
High Intensity Use
7.6E-02
7.1E-02
7.7E-02
CEM
(Permeability)
Moderate Intensity Use
3.8E-02
3.5E-02
3.9E-02
Low Intensity Use
1.3E-02
1.2E-02
1.3E-02
Spray Cleaner-General
High Intensity Use
3.6
3.3
3.6
CEM
(Permeability)
Moderate Intensity Use
0.44
0.42
0.45
Low Intensity Use
5.9E-02
5.5E-02
6.1E-02
Adhesive Accelerant
High Intensity Use
4.8E-02
4.5E-02
4.9E-02
CEM (Fraction
Absorbed)
Moderate Intensity Use
4.8E-02
4.5E-02
4.9E-02
Low Intensity Use
4.8E-02
4.5E-02
4.9E-02
Automobile AC Flush
High Intensity Use
0.50
0.47
0.52
CEM (Fraction
Absorbed)
Moderate Intensity Use
0.50
0.47
0.52
Low Intensity Use
0.50
0.47
0.52
Mold Cleaning and Release
Product
High Intensity Use
4.3E-02
4.0E-02
4.4E-02
CEM (Fraction
Absorbed)
Moderate Intensity Use
2.8E-02
2.6E-02
2.9E-02
Low Intensity Use
1.5E-02
1.4E-02
1.5E-02
The maximum inhalation concentration modeled for the consumer user and bystander occurred
under the high intensity use scenario for an aerosol spray degreaser/cleaner-general condition of
use. The minimum inhalation concentration modeled for the consumer user and bystander both
occurred under the low intensity use scenario for the aerosol spray cleaner/degreaser-electronics
condition of use.
Across all consumer uses modeled for dermal exposure, the maximum ADD for the Adult user
occurred under the high intensity use scenario for the spray cleaner-general condition of use. The
maximum ADD for the Youth A and Youth B users occurred under the high intensity use scenario
of both the spray cleaner-general condition of use and the aerosol spray degreaser/cleaner-general
condition of use. The minimum ADD for all three users (Adult, Youth A, and Youth B), occurred
under the low intensity use scenario for the spot cleaner/stain remover condition of use.
Insulation Results
EPA evaluated the insulation (off-gassing) condition of use for both acute and chronic exposures.
Unlike the other conditions of use summarized above, which cause a short-term, higher-level
exposure, installation of the rigid installation board causes both a short-term, higher-level exposure
(initial spike in concentrations from off-gassing for the first few days) and a long-term, lower-level
exposure (rapid decrease in concentration from off-gassing reaching a relatively consistent
concentration after the first few months). This can be seen in Figure 2-17 and Figure 2-18.
Page 166 of 486
-------
ttic
4 4
<
-------
Table 2-57. Inhalation Results Summary-Insulation (Off-Gassing)
Condition of Use
Scenario
Description
Bystander Exposure Concentration (ppm)
Model Used
24-hour TWA
7-Year Average TWA
Insulation (Off-gassing)
Attic/Living Space/Crawlspace
Attic
2.0E-03
4.9E-05
IECCU
Living Space
9.0E-04
2.0E-05
Crawlspace
2.1E-03
4.4E-05
Insulation (Off-gassing)
Attic/Living Space/Basement
Attic
2.0E-03
4.8E-05
IECCU
Living Space
3.2E-04
7.9E-06
Basement
2.1E-03
4.6E-05
Considering the likely locations where an individual may spend most of their time within a
residence, the concentrations within the living space of both building configurations and the
basement of the attic/living space/basement building configuration are of particular interest for
both short-term and long-term inhalation exposures. Concentrations within the attic can be a factor
to consider for short-term and long-term inhalation exposures if the attic was converted to a living
space, play area, or bedroom, as was sometimes done in older residences or some modern
renovations to garner more usable space. Outside of conversion of the attic to a usable space, the 7-
year average values for the attic and crawlspace would be more representative of a short-term
exposure to individuals entering the area for a short period of time to remove items stored, do some
other applicable repair work, or clean out the area beginning several months after initial installation
of the rigid insulation board.
2.3.2.6 Key Assumptions, Uncertainties, and Confidence
Modeling was used to evaluate consumer exposure concentrations under the conditions of use
summarized in Table 2-31. This modeling required a variety of inputs when data were available. In
the absence of available data, this modeling relied on certain default data values and certain
assumptions. As with any risk evaluation, there are uncertainties associated with the data used,
assumptions made, and approaches used. An overall review of these three factors can help develop
a qualitative description of the confidence associated with these factors and results obtained.
Key Assumptions and Uncertainties
Consumer exposure for this risk evaluation is based on the assumption that the product used under
the conditions of use (Table 2-31) was only used once per day. This assumption considers a single
use event occurring over a certain period of time and represents an expected consumer use pattern.
This assumption applies to all conditions of use evaluated (except for the insulation (off-gassing)
condition of use). There is a low uncertainty associated with this assumption because most
consumer products are used for a single use over a short-period of time. Additional uses which
may occur within a given year are expected to occur well after the first use and typically would
occur after the concentration from the original use decreases to background levels.
Page 168 of 486
-------
Exposure for the insulation (off-gassing) condition of use assumes the rigid board insulation is
installed in each location (attic and crawlspace/basement) within a single day and remains installed
for an extended period of time. This assumption considers short-term initial exposure from off-
gassing due to the initial spike in 1-BP concentrations immediately following installation as well as
long-term exposure from off-gassing following the initial spike in 1-BP concentrations. There is a
low uncertainty associated with this assumption because the rigid board insulation's intended use is
a permanent installation over an extended period of time. Unlike the other conditions of use
evaluated, however, off-gassing of 1-BP is continuous for years after initial installation.
Consumer exposure for this evaluation is also based on the assumption that a single product is used
for a single day under a specific condition of use. There is a medium-low uncertainty associated
with this assumption because certain consumer activities (like cleaning) may entail the use of more
than one cleaning product within a particular condition of use. However, there remains some
uncertainty because even if more than one cleaning product is used, to impact the estimated
exposure in this evaluation, each product used would have to contain 1-BP and therefore result in a
higher overall exposure.
This evaluation assumes consumer exposure under each condition of use (excluding insulation
(off-gassing)) is not chronic in nature due to the infrequent use and short duration of use for a
given product. There is a medium uncertainty associated with this assumption because, although
information found during EPA's systematic review process supports infrequent use and short
durations of use, there is a growing consumer practice to do-it-yourself projects or activities which
could lead to increased frequencies of use and the possibility of more than one product containing a
chemical of concern within a given day.
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. There is a low uncertainty associated with this assumption.
Selection of Models Used
Inhalation Models: Three peer reviewed EPA models were used to estimate inhalation exposure to
the consumer user or bystander (CEM, MCCEM, and IECCU) in this evaluation. These models
were selected as fit-for-purpose models which had pre-defined exposure scenarios comparable to
the expected consumer use exposure scenarios. Each model has certain limitations and
uncertainties within the model or associated with inputs or default values utilized by the models.
Limitations of the models were considered as part of the selection process for each condition of
use. For example, neither CEM nor IECCU have a scenario designed for a pool of liquid (coin and
scissors cleaner or automobile AC flush), but MCCEM had two applicable models. Similarly,
IECCU is an indoor air pollution transport model which can consider seasonal variation while
CEM and MCCEM do not have that capability.
The selection and use of these models, even considering limitations, inherently have some
uncertainty. Applying fit-for-purpose concepts and considering limitations of each model helps to
Page 169 of 486
-------
reduce uncertainties and increase confidence in the overall model selected. EPA has an overall low
uncertainty in the models utilized for estimating inhalation exposure.
Dermal Models: Three models were considered for estimating dermal exposure to the consumer
user (CEM (Fraction Absorbed), CEM (Permeability), and a full transient exposure model based
on a published paper from Frasch (Frasch and Bunge. 2015)) in this evaluation. EPA evaluated
each model, the inputs and outputs associated with each model, the applicability of each model to
the expected consumer dermal exposure scenarios for each condition of use, and applied a fit-for-
purpose approach to selecting the final models used to estimate consumer dermal exposures. A
comparison and sensitivity analysis of all three models (including results) is provided in Appendix
F.
Utilizing the process described above, EPA selected two models for estimating dermal exposure to
the consumer user (CEM (Fraction Absorbed) and CEM (Permeability)) for this evaluation. The
CEM (Fraction Absorbed) model was selected for those COUs where evaporation is uninhibited
and where full immersion of body parts is not expected during use. The basis for this selection is
that CEM (Fraction Absorbed) is a mass limited model which considers evaporation from the skin
and only the fraction absorbed portion of the total exposure occurring during product use. To
minimize uncertainty, this model was run utilizing the assumption that the entire mass of chemical
in the thin film enters the stratum corneum. With this assumption, the CEM (Fraction Absorbed)
model correctly applies the fraction absorbed component to the chemical retained within the skin
rather than on the skin. Additionally, while the estimated absorption coefficient (Kp) within the
CEM (Fraction Absorbed) model is based on an aqueous vehicle, a neat Kp was obtained from
literature and incorporated into the model. The use of the neat Kp is more representative of the
products identified within the various COUs for which this model was utilized as most products
were not aqueous (in water) but rather in other carbon based solvent media and had a chemical
specific weight fraction of 50 to 100 percent.
The CEM (Permeability) model was selected for those COUs where evaporation is
inhibited/prohibited or where full immersion of body parts is expected during use. The basis for
this selection is that CEM (Permeability) does not consider evaporation from the skin and assumes
a constant supply of product against the skin during the entire duration of use. Similar to CEM
(Fraction absorbed), the CEM (Permeability) model estimates the permeability coefficient based on
an aqueous vehicle. To minimalize uncertainty, the CEM (Permeability) model was run utilizing a
neat (Kp) value obtained from published literature and evaluated in accordance with EPA's
systematic review process. The use of the neat Kp is more representative of the products identified
within the various COUs for which this model was utilized as most products were not aqueous (in
water) but rather in other carbon based solvent media and had a chemical specific weight fraction
of 50 to 100 percent.
While the model presented in (Frasch and Bunge. 2015) is mathematically more complete than
CEM (Fraction Absorbed), it is not applicable to splash or similar dermal exposure scenarios
expected for the COUs where CEM (Fraction Absorbed) is utilized. Additionally, the published
model in (Frasch and Bunge. 2015) has certain variables which are based on aqueous vehicles of
Page 170 of 486
-------
delivery. To utilize this model for solvent-based vehicles of delivery would require modifications
to the published method which are not necessary when utilizing the CEM (Fraction Absorbed) of
CEM (Permeability) model.
The selection and use of the two CEM models, even considering limitations, inherently have some
uncertainty. Applying fit-for-purpose concepts and considering limitations of each model helps to
reduce uncertainties and increase confidence in the overall model selected. EPA has an overall low
confidence in the models utilized for estimating dermal exposure based primarily on the
uncertainties associated with aqueous/solvent-based vehicles, revisions to model approaches with
neat Kp values vs. aqueous Kp values as well as other factors identified in Appendix F.
Inputs and Uncertainties
Inputs for modeling in this evaluation were a combination of physical-chemical properties of 1-BP,
default values within the models used, values from U.S. EPA's Exposure Factors Handbook (U.S.
EPA. 2011). Westat Survey (EPA. 1987). and other data found in the literature as part of the
systematic review process. Physical-chemical properties of 1-BP are pre-defined and well-
established in the literature. These properties do not change under standard conditions and
therefore have very low uncertainty 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 U.S. EPA's Exposure
Factors Handbook (U.S. EPA. 2011). The models used have a variety of default values as well as
some estimation methodologies which were relied upon as part of this evaluation. There is a
medium-low uncertainty associated with these values due to the number of parameters where
defaults are available.
Values from U.S. EPA's Exposure Factors Handbook (U.S. EPA. 2011) 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 low uncertainty associated with the values in U.S. EPA's Exposure Factors
Handbook (U.S. EPA. 2011).
Multiple aspects of the Westat Survey (EPA. 1987) were utilized in this evaluation including cross-
walking conditions of use evaluated with one of the thirty-two product categories within the
survey; frequency of use, duration of use, and room of use for cross-walked product categories;
and other information utilized to inform approaches taken. Most of the consumer uses summarized
in Table 2-31 aligned well with one of the thirty-two product categories within the Westat Survey.
There is a medium-low uncertainty associated with the cross-walking of consumer uses with the
Westat product categories.
The representativeness of the information extracted for modeling from the cross-walked product
categories within the Westat Survey (EPA. 1987) aligns well with expected modern day consumer
patterns. However, there is uncertainty associated with the age of the Westat Survey in that it may
not be fully representative of modern day consumer activities and products like do-it-yourself
hobbyists, modified uses, more concentrated formulations, ease of access to products, or similar
Page 171 of 486
-------
changes which have occurred. There is a medium uncertainty associated with the
representativeness of the consumer use patterns described within the Westat Survey and modern
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 2.3.2.1, EPA's Preliminary Information on Manufacturing, Processing,
Distribution, Use, and Disposal: 1-Bromopropane document (U.S. EPA. 2017c) included in the
docket for this risk evaluation (Docket Number EPA-HQ-OPPT-2016-0741 -0003). is based on
information available at that time. It does not take into consideration company-initiated
formulation changes, product discontinuation, or other business or market based factors that
occurred after the document was compiled. There is a medium uncertainty associated with the
information included in the document.
There are multiple model specific factors to which a level of uncertainty may apply including user
groups (age groups) evaluated, building characteristics, and default model parameters. There is a
medium level of uncertainty associated with the appropriateness of considering all three age groups
(Adult, Youth A and Youth B) as users for dermal exposure in this evaluation. As discussed in
Section 2.3.2.2, the lower end of the Youth B age group (11-13 years of age) are possible users but
not necessarily reasonably foreseeable users of high solvent products identified in the conditions of
use evaluated, with the exception of perhaps the coin and scissors cleaner condition of use.
However, the upper end of the age group (14-15 years of age) are possible and reasonably
foreseeable users of the same products in the context of cleaning chores or learning general
automobile care from parents, friends, shop classes, or hobbyist activities like dirt bikes or go carts.
There are multiple building characteristics considered when modeling consumer exposure
including, but not limited to, room size, ventilation rate, and building size. For this evaluation,
EPA relied on default values within the models for these parameters. These default values were
primarily obtained from U.S. EPA's Exposure Factors Handbook (U.S. EPA. 2011). There is a low
uncertainty associated with these parameters.
Room size varied for this evaluation based on room of use obtained from the Westat Survey (EPA.
1987) data. Room size relates to the volume of the 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 relatively 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 and 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 low uncertainty associated with room sizes used for this
evaluation.
Page 172 of 486
-------
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 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 low uncertainty 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 low uncertainty associated with building
size.
EPA assumes consumers will not wear personal protective equipment (PPE) and will not use
complex engineering controls like hoods, baghouses, or incineration devices during product use.
Even if basic PPE like gloves or eye protection is used, EPA cannot assume the appropriate PPE
will be selected or that consumers will use the PPE correctly. There is low uncertainty associated
with these assumptions as 1-BP requires highly specialized gloves to adequately protect against
exposure, and neither gloves nor eye protection protects against inhalation exposure.
Confidence
Inhalation Models and Results: There is an overall high confidence in the three models used to
evaluate inhalation exposure and the inhalation results found for the conditions of use identified in
Table 2-31. This confidence derives from a review of the factors discussed above as well as
previous discussions about the strength of the models and data used, sensitivity of the models, and
approaches taken for this evaluation.
All three models used for this evaluation are peer reviewed models. The models themselves were
used for this evaluation as they were developed and designed to be used. The equations within the
models 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
models (and retained for this evaluation) are a combination of central tendency and high-end
estimates from both peer reviewed literature and U.S. EPA's Exposure Factors Handbook (U.S.
EPA. 2011). The approaches taken for this evaluation cover a spectrum of modeling results
representative of expected consumer use patterns. Even though some default values have high-end
values (like building size or ventilation rates), it should be recognized that the sensitivity of these
parameters are actually negative and the "higher" building sizes or higher ventilation rates would
Page 173 of 486
-------
result in more mixing and dissipation leading to lower exposure concentrations and therefore a less
conservative exposure estimate.
The data used in lieu of default values within the model are a combination of low, central
tendency, and high-end values from the Westat Survey (EPA. 1987) which was rated as a high
quality study as part of the systematic review process. The nine conditions of use evaluated align
well with specific scenarios within the Westat Survey (EPA. 1987). pre-defined model scenarios,
and other approaches taken. The deterministic approach taken for consumer inhalation exposure in
this evaluation varies three parameters which are highly sensitive, representative of consumer use
patterns, or both. The three parameters varied also provide 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.
Dermal Models and Results: There is an overall low confidence in the two models used to evaluate
dermal exposure and the dermal results found for the conditions of use identified in Table 2-31.
This confidence derives from the limitations and uncertainties inherent within the two dermal
models, including aqueous delivery vehicles and the use of solubility rather than density in several
sub-equations within the models. These limitations were minimized by using a neat-based Kp and
experimental absorption coefficient where allowed. The assumptions necessary to correctly apply
the two models used for dermal modeling tend to result in an overestimation of exposure for a
typical consumer user (single product, infrequent use, shorter duration of use), although absent
monitored data, a more conservative estimate is preferred to ensure potential risks are captured.
2.4 Potentially Exposed or Susceptible Subpopulations
TSCA § 6(b)(4)(A) 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 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 infants, children, pregnant women, workers, or the elderly."
For occupational exposures, EPA assessed exposures to workers and ONUs from all 1-BP
conditions of use. Table 2-58 presents the percentage of employed workers and ONUs who may be
susceptible subpopulations within select industry sectors relevant to 1-BP conditions of use. The
percentages were calculated using Current Population Survey (CPS) data for 2017. CPS is a
monthly survey of households conducted by the Bureau of Census for the Bureau of Labor
Statistics (BLS) and provides a comprehensive body of data on the labor force characteristics.
Statistics for the following subpopulations of workers and ONUs are provided: individuals age 16
Page 174 of 486
-------
to 19, men and women of reproductive age,28 and the elderly. For the purpose of this risk
evaluation, EPA considers "reproductive age" as age 16 to 54. As shown in Table 2-58, men make
up the majority of the workforce in manufacturing sectors. In other sectors, women (including
those of reproductive age and elderly women) make up nearly half of the workforce.
Adolescents (16 to <21 years old) appear to be generally a small part of the total workforce based
on CPS data for employed individuals between 16 and 19 years of age. Table 2-59 presents further
breakdown on this subset of adolescents employed by industry subsectors. As shown in the table,
they comprise less than two percent of the workforce, with the exception of repair and maintenance
subsector where 1-BP may be used in aerosol degreasing, and the dry cleaning subsector where 1-
BP may be used for dry cleaning and spot cleaning. These data do not cover all adolescents in the
1-BP workforce because of the different age range used by the BLS.
Table 2-58. Percentage of Employed Persons by Age, Sex, and Industry Sector
Age group
Sex
Manufacturing
Wholesale and
retail trade
Professional and
business
services
Other services
16-19 years
Male
0.8%
3.0%
0.7%
1.4%
Female
0.4%
3.2%
0.5%
1.7%
Reproductive age
(16-54 years)
Male
52.9%
42.8%
44.4%
35.2%
Female
22.2%
35.4%
32.8%
38.4%
Elderly (55+)
Male
17.5%
12.3%
13.4%
13.1%
Female
7.3%
9.6%
9.4%
13.3%
Source: (U.S. BLS. 2017). Percentage calculated using CPS table 14, "Employed persons in nonagricultural industries
by age, sex, race, and Hispanic or Latino ethnicity."
Table 2-59. Percentage of Employed Persons Age 16-19 Years by Detailed Industry Sector
Sector
Subsector
Age: 16-19 years
Manufacturing
All
1.2%
Wholesale and retail trade
Wholesale trade
1.4%
Professional and business services
Waste management and remediation services
0.9%
Other services
Repair and maintenance
3.1%
Drycleaning and laundry services
3.7%
Source: (U.S. BLS. 2017). Percentage calculated using CPS table 18b, "Employed persons by detailed industry and
age."
28 While statistics on pregnant women are not available, CPS provides data on the number of employed female workers
by age group, which allows for determination of the number of employed women of reproductive age.
Page 175 of 486
-------
The CPS uses 2012 Census industry classification, which was derived from the 2012 NAICS. The
Census classification uses the same basic structure as NAICS but is generally less detailed. 1-BP
conditions of use fall under the following Census industry sectors:
• Manufacturing - The Manufacturing sector comprises establishments engaged in the
mechanical, physical, or chemical transformation of materials, substances, or components into
new products. Establishments in the sector are often described as plants, factories, or mills. For
1-BP, this sector covers most conditions of use that occur in an industrial setting, including:
Manufacturing, Processing as a reactant, Processing - Incorporation into formulation, mixture,
or reaction product, Incorporation into Articles, Spray adhesives, and the vast majority of
facilities likely engaged in Vapor Degreasing (all degreaser types) and Cold Cleaning. This
sector also covers cement manufacturing facilities that may burn waste containing 1-BP for
energy recovery.
• Wholesale and retail trade - The wholesale trade sector comprises establishments engaged in
wholesaling merchandise, generally without transformation, and rendering services incidental
to the sale of merchandise. Wholesalers normally operate from a warehouse or office. This
sector likely covers facilities that are engaged in the importation of 1-BP or products and
formulations containing 1-BP. The retail trade sector comprises establishments engaged in
retailing merchandise and rendering services incidental to the sale of merchandise.
• Professional and business services - This sector comprises establishments that specialize in a
wide range of services. This sector covers waste management and remediation services, which
includes establishments that may handle, dispose, treat, and recycle wastes containing 1-BP.
• Other services - This sector comprises establishments engaged in providing services not
specifically provided for elsewhere in the classification system. For 1-BP, this sector covers the
vast majority of commercial repair and maintenance facilities that are likely to use 1-BP for
aerosol degreasing. The sector also covers the use of 1-BP in dry cleaning and spot cleaning.
For consumer exposures, EPA assessed exposures to users and bystanders. EPA assumes, for this
evaluation, consumer users are male or female individuals (between 11 and 21 years of age and
greater than 21 years of age). Bystanders could be any age group ranging from infants to adults
(Section 2.3.2.1).
This assessment qualitatively evaluates consumer exposure for potentially exposed susceptible
subpopulations (PESS). PESS can include reproductive age females who may be or become
pregnant; lactating women; reproductive age males; infants, toddlers, children at various
developmental stages in life, and elderly; individuals of any age with health issues or concerns
including suppressed immune systems, asthma, chemical sensitivity, heart disease, or other health
issues or concerns. PESS can be a consumer user or bystander depending on the individuals age
and location during product use.
Additional PESS groups include people with implantable prosthetics because 1-BP is an available
cleaner for implantable prosthetic devices (https://www.albemarle.com/businesses/bromine-
specialties/bromine-&-derivatives/specialtv-chemicals).
Page 176 of 486
-------
3 HAZARDS (Effects)
3.1 Environmental Hazards
3,1,1 Approach and Methodology
In the Problem Formulation (U.S. EPA. 2018c). EPA performed quantitative and qualitative
screening-level analysis to determine which pathways to include in the scope of the risk evaluation.
The qualitative aspect of the assessment considered the physical-chemical properties of 1-BP as
well as the conditions of use within the scope of the risk evaluation to determine whether potential
exposures to terrestrial species from air releases, water releases or land application of biosolids
could present a risk concern. This qualitative assessment indicated that exposures and risks to
terrestrial receptors are not expected and no further analysis is necessary (U.S. EPA. 2018c).
Similarly, potential concerns for aquatic sediment-dwelling species were assessed by considering
the potential for exposure given the physical chemical properties of 1-BP in water, which indicated
that risks are not expected. Consistent with the analysis plan of the Problem Formulation (U.S.
EPA. 2018c). no further analysis of hazards to sediment-dwelling aquatic or terrestrial species was
carried out as part of this evaluation and the results presented below are brought forward from the
problem formulation to make a risk determination for these species because the initial evaluation
was sufficient to make a risk determination for these organisms.
The quantitative aspect of this risk evaluation compared hazard threshold concentrations for water
column-dwelling aquatic species (calculated using an acute fish study identified during the
literature search for 1-BP as well as environmental hazard endpoints estimated using the
Ecological Structure Activity Relationships (ECOSAR, v.2.029) modeling program) with estimated
environmental exposure concentrations in the water column resulting from discharges of 1-BP to
surface water. This aspect of the analysis has been updated in this final risk evaluation due to
uncertainties about the data presented in the Problem Formulation and draft risk evaluation which
utilized hazard data summaries presented in the European Chemical Health Agency (ECHA)
REACH registration page for 1-BP. The results presented in these ECHA summaries are not
utilized in this final risk evaluation, as EPA was unable to identify a US-based data owner and
could not obtain the full study reports for these summaries. The results of this updated quantitative
analysis for aquatic species indicated that risks to aquatic species are unlikely and no further
analysis is necessary.
EPA identified environmental hazard data through a literature search for 1-BP as outlined in 1-
Bromopropane (CASRN106-94-5) Bibliography: Supplemental File for the TSCA Scope
Document, EPA-HQ-OPPT-2016-0741 -0047. As described below, a total of one on-topic
environmental hazard study (acute fish study; (Geiger et al.. 1988) was identified and reviewed
according to the systematic review criteria described in Application of Systematic Review in TSCA
29 More information about the ECOSAR program can be found at: https://www.epa.gov/tsca-screening-
tools/ecological-structure-activitv-relationships-ecosar-predictive-model
Page 177 of 486
-------
Risk Evaluations (U.S. EPA. 2018a) and Strategy for Assessing Data Quality in TSCA Risk
Evaluations (U.S. EPA. 2017e). This study was determined to be high quality following data
quality evaluation; the full study quality evaluation is presented in the systematic review data
evaluation document for ecological hazard studies (EPA. 2019k).
Five robust data summaries were identified in the European Chemicals Agency (ECHA) database
to characterize the environmental hazards of 1-BP to aquatic receptors (ECHA. 2017). These data
summaries were not utilized in the final risk evaluation because the full study reports could not be
obtained by the EPA and reviewed for data quality. To reduce uncertainties about relying on a
single acute toxicity study with fish to draw conclusions about the environmental risks across all
species, EPA utilized the Ecological Structure Activity Relationships (ECOSAR, v.2.030) program
to estimate the acute (short-term) toxicity and chronic (long-term or delayed) toxicity to aquatic
organisms from exposure to 1-BP. This utilizes quantitative structure activity relationships
(QSARs) to predict the aquatic toxicity based on a similarity of the structure to chemicals for
which the aquatic toxicity has been previously measured. ECOSAR relies on a linear mathematical
relationship between the predicted log Kow values and the corresponding log of the measured
toxicity values within the training set of chemicals for each class of interest (in the case of 1-BP,
this class is neutral organics). The results of this modeling is presented in Table 3-1 and the
modeling output is presented in Appendix G.
3.1.2 Hazard Identification- Toxicity to Aquatic Organisms
Two notable updates to the analysis of environmental hazard were made to the environmental
hazard conclusions of this document. First, EPA evaluated reasonably available environmental
hazard data for 1-BP for data quality (EPA. 2019k). Second, EPA was unable to obtain the full
study reports for the data summaries identified in the ECHA Database and presented in the draft
risk evaluation so these data could not evaluated according to the systematic review criteria and
were not included in the final risk evaluation. To assess aquatic toxicity from acute exposures,
acute exposure toxicity data for fish were identified. The results of these studies are discussed
below and summarized in Table 3-1. The acute fish toxicity study by (Geiger et al.. 1988). was
conducted with fathead minnows (Pimephalespromelas) over a 96 hour exposure period. This
study was conducted as part of a multi-investigator effort, led by the U.S. EPA Environmental
Research Laboratory in Duluth, MN and the University of Wisconsin-Superior in Superior, WI.
The goal of this effort was to generate a systematic database of acute toxicity data for a variety of
organic chemicals for use by regulatory and academic communities to support advances in the
development of quantitative structure-activity relationship (QSAR) models. This effort resulted in
a multi-volume report. In addition to toxicity data for 1-BP, the cited volume contained acute fish
toxicity data for several dozen organic chemicals across 24 chemical classes, all of which were
conducted according to procedures which are outlined in the introduction of the publication. The
experimental procedures used in this effort represent the best practices for conducting acute
30 More information about the ECOSAR program can be found at: https://www.epa.gov/tsca-screening-
tools/ecological-structure-activitv-relationships-ecosar-predictive-model
Page 178 of 486
-------
toxicity testing with fathead minnows and are consistent with the test guidelines currently
recommended by EPA and international regulatory partner organizations for conducting ecological
risk assessment purposes for fish. Because this effort was funded and led by EPA, it was conducted
according to the editing, quality assurance and peer review procedures set forth by EPA as a
requirement for the publication of empirical test data to be used in regulatory science. An LC50
value of 67.3 mg/L (based on measured test concentrations) was reported based on mortality
observed in the test organisms (Geiger et al.. 1988). The study authors reported sublethal effects
that included a loss of schooling behavior, hypoactivity, underreactivity to external stimuli,
increased respiration, dark coloration and loss of equilibrium prior to death. This study was
evaluated by EPA under EPA's TSCA Systematic Review Process for data quality and determined
to be high quality (EPA. 2019k). In addition, ECOSAR (v2.0) predicted toxicity value for fish is
72.9 mg/L. The acute toxicity estimate for aquatic invertebrates predicted by ECOSAR (v.2.0) is
42.0 mg/L, while the algae EC50 value predicted by ECOSAR is 33.2 mg/L. The ECOSAR-
predicted toxicity values for acute and chronic exposure to fish, aquatic invertebrates and algae
also available in Table 3-1, which supports EPA's weight of scientific evidence conclusions.
The vapor pressure of 1-BP is 110 mm Hg at 20°C and the Henry's law constant is calculated to be
over 700 Pa.M3/mol. These physical-chemical properties input to the WVol model in EPISuite
indicate that 1-BP will volatilize from a model river with a half-life on the order of an hour and
from a model lake on the order four days. Although volatilization is expected to be rapid, a Level
III Fugacity model predicts that when 1-BP is continuously released to water, 80% of the mass will
be in water 19% in air due in part to its water solubility. Intermittent releases of 1-BP are not
expected to result in long-term presence in the aquatic compartment. Chronic exposure is only a
likely scenario for environments near continuous direct release sites. As no data were available to
characterize the hazards of chronic exposure to aquatic species, EPA estimated hazards from
chronic exposure using an acute-to-chronic ratio (ACR). The most sensitive species following
acute exposure, freshwater fish reported a 96-hr LC50 of 67.3 mg/L the value (Geiger et al.. 1988)
was divided by an ACR of 10 to estimate the toxicity to fish following chronic exposure. This
results in a fish chronic value (ChV) of 67.3 mg/L/ 10= 6.73. The chronic toxicity value for fish
predicted by ECOSAR is 7.24 mg/L, while the chronic toxicity value for aquatic invertebrates is
4.26 mg/L. The ECOSAR predictions for 1-BP are summarized below in Table 3-1.
3,1.3 Hazard Identification- Toxicity to Terrestrial Organisms
1-BP is expected to be present at limited concentrations in terrestrial ecosystems. As a result of
high volatility (Vapor Pressure= 110 mm Hg at 20°C; Henry's Law constant of 7.3xl0"3 atm-
m3/mole; see Table 1-1) and conditions of use of the chemical, it is expected that 1-BP will only be
present in terrestrial environmental compartments as a transient vapor. No specific conditions of
use {i.e., systematic application to land) were identified that resulted in systematic, significant
airborne exposures that overlap with terrestrial habitats, so this is not a relevant route of exposure
for 1-BP under the conditions of use of this risk evaluation. Additionally, 1-BP is not expected to
bioaccumulate (BAF=12; BCF=11, see Table 2-1) which means that exposures to terrestrial
species through oral routes is limited. This preliminary conclusion, which was presented in the
Problem Formulation, is confirmed in this final risk evaluation; no further analysis of hazards to
Page 179 of 486
-------
terrestrial receptors was carried out as part of this evaluation, as exposure to terrestrial species is
not expected.
3.1,4 Weight of the Scientific Evidence
During the data integration stage of EPA's systematic review, EPA analyzed, synthesized, and
integrated reasonably available data/information. This involved weighing scientific evidence for
quality and relevance, using a Weight of the Scientific Evidence (WoE) approach (U.S. EPA.
2018a). The ecological risk assessor decided if data/information were relevant based on whether it
has biological, physical-chemical, and environmental relevance (U.S. EPA. 1998a):
• Biological relevance: correspondence among the taxa, life stages, and processes measured
or observed and the assessment endpoint.
• Physical-chemical relevance: correspondence between the chemical or physical agent tested
and the chemical or physical agent constituting the stressor of concern.
• Environmental relevance: correspondence between test conditions and conditions in the
region of concern. (U.S. EPA. 1998a)
A single acute fish toxicity study was used to conduct a screening-level characterization of the
environmental hazards of 1-BP. EPA was unable to obtain the full environmental hazard studies
that were summarized in the ECHA database and these studies could not be evaluated for data
quality, so EPA chose not to include these study summaries in the final risk assessment (The
studies were in French and Japanese with no U.S.A. sponsor). As a result, only a single acute fish
toxicity study identified during the literature search process (Geiger et al.. 1988) has been
evaluated according to the systematic review criteria in The Application of Systematic Review in
TSCA Risk Evaluations and was determined to be of high quality (Geiger et al.. 1988) (U.S. EPA.
2018a). While this peer reviewed study was determined to be of high quality, the lack of data for
other aquatic species led to some uncertainty about whether this single study was appropriate to
estimate environmental hazards across species. To reduce uncertainty about the lack of
environmental hazard data, QSAR modeling outputs provided by ECOSAR (v2.0) (EPA. 2017)
were used in the assessment. The acute toxicity study and ECOSAR modeling outputs both
indicate that 1-BP presents a moderate hazard to aquatic environmental receptors31. While
empirical data are not available to characterize the hazards of 1-BP to aquatic invertebrates and
algae, ECOSAR modeling is appropriate for 1-BP. ECOSAR-predictions for 1-BP are based on the
neutral organics chemical class. Of the 120 chemical classes within ECOSAR, this class is the
largest and most robust. The dataset used to generate the regression equation to predict hazards of
acute exposure to chemicals within the neutral organics chemical class contains 296 data points for
fish, 147 for aquatic invertebrates, and 66 for algae. The dataset used to generate the regression
31 Hazard concern levels for acute exposure: Low >100mg/L; Moderate >1.0 mg/L and <100 mg/L; High <1.0. Hazard
concern levels for chronic exposure: Low >10 mg/L; Moderate >0.1 mg/L and <10 mg/L; High <0.1 (U.S. EPA.
2012e).
Page 180 of 486
-------
equation used to predict hazards from chronic exposure contains 46 data points for fish, 26 for
daphnia and 34 for algae. In addition, the majority of the data that comprise the QSAR training set
in the neutral organics chemical class were generated as part of the same research effort as the high
confidence acute fish toxicity test for 1-BP (Geiger et al.. 1988). While the acute toxicity data for
1-BP are not specifically included in the QSAR training set for neutral organic chemicals in
ECOSAR, there are several organic chemicals with a similar log Kow and molecular weight that
are in the training set such as analogous chemicals N,N-Dimethylaniline (MW 121, Log KOW=
2.31) and 6-Methyl-5-hepten-2-one (MW=126, LogKOW=2.1) with similar measured toxicity
values for fish that indicate 1-BP is well-characterized by the neutral organics chemical class. The
acute toxicity study and ECOSAR modeling outputs both indicate that 1-BP presents a moderate
hazard to aquatic environmental receptors.
3,1,5 Concentrations of Concern (COCs)
The acute and chronic concentrations of concern (COCs) for aquatic species were calculated based
on the results of the high quality study (Geiger et al.. 1988). An uncertainty factor (UF; also
referred to as an assessment factor (AF)) is applied according to EPA methods (Suter. 2016) (U.S.
EPA. 2012e) (U.S. EPA. 2013b). The application of AFs provides a lower bound effect level that
would likely encompass more sensitive species not specifically represented by the available
experimental data. AFs also account for differences in inter- and intra-species variability, as well as
laboratory-to-field variability. These assessment factors are dependent upon the availability of
datasets that can be used to characterize relative sensitivities across multiple species within a given
taxa or species group. The assessment factors are often standardized in risk assessments conducted
under TSCA, since the data available for most industrial chemicals are limited. For fish and aquatic
invertebrates (e.g., daphnia), the acute COC values are divided by an AF of 5. For chronic COCs ,
and to calculate a COC for algae, where multiple generations can be present over the course of a
standard toxicity test, an AF of 10 is used.
3.1.5.1 Acute COC:
As described above, the 96-hour LCso value for 1-BP that was reported in the high quality study is
67.3 mg/L (Geiger et al.. 1988). This high quality value was then divided by the AF of 5 for fish
and then multiplied by 1,000 to convert from mg/L to (ig/L, or ppb. To reduce uncertainty related to
the lack of data available to characterize the hazard of 1-BP to aquatic species, a COC was also
calculated using the ECOSAR-predicted endpoints for acute exposure, as presented in Table 3-1.
• The acute COC for 1-BP, based on 96-hour fish toxicity LCso is: (67.3 mg/L) / AF of 5 x 1,000
= 13,460 |ig/L or ppb.
• To provide additional characterization of potential risks from acute exposure to 1-BP, a COC
based on the most sensitive species for acute exposure as predicted by ECOSAR, which is
algae: (33.2 mg/L) / AF of 10 x 1,000 = 3,320 |ig/L or ppb.
Page 181 of 486
-------
3.1.5.2
Chronic COC:
Since there are no long-term chronic studies for 1-BP, the fish 96-hr LC50 of 67.3 mg/L (the value
in the dataset derived from the high quality toxicity study; is divided by an acute-to-chronic ratio
(ACR) of 10 to obtain a chronic value (ChV) for fish (Geiger et al.. 1988). The fish ChV is then
divided by an AF (10), and then multiplied by 1,000 to convert from mg/L to |ig/L, or ppb to obtain a
chronic COC. The ECOSAR modeling results indicate that the relationship between predicted
acute and chronic hazard is close to 10 for 1-BP (ECOSAR-estimated Fish 96 hr LCso=72.9 mg/L,
Fish ChV=7.24 mg/L; Daphnid 48 hr LCso=42.0 mg/L, Daphnid ChV=4.26 mg/L). This supports
the use of an ACR of 10 to estimate hazards from chronic exposure to 1-BP.
• The Chronic COC for 1-BP, based on an estimate of the chronic hazard to fish is (67.3 mg/L) /
10 (ACR) / AF of 10 x 1000 = 0.673 mg/L or 673 |ig/L or ppb.
• To provide additional characterization of potential risks from chronic exposure to 1-BP, a COC
based on the most sensitive species for chronic exposure as predicted by ECOSAR, which are
aquatic invertebrates: (4.26 mg/L) / AF of 10 x 1,000 = 426 |ig/L or ppb.
3.1.6 Hazard Summary
1-BP presents a moderate hazard (according to the concern levels outlined in U.S. EPA (2012e)32)
to aquatic species based on data characterizing the effects of acute exposure to fish and ECOSAR
predictions for acute and chronic exposure to fish, aquatic invertebrates and algae. Sublethal
effects reported following acute exposure to fish included darkened pigmentation, and loss of
orientation were observed in test organisms at lower concentrations, but specific concentrations
where these were observed were not reported (Geiger et al.. 1988). Acute to chronic extrapolation
indicates that effects in fish following chronic exposure to 1-BP are estimated to occur at 6.73
mg/L.
This conclusion of moderate environmental hazard is supported by QSAR modeling outputs
provided by ECOSAR (v2.0) (EPA. 2017) where moderate hazard was reported for all aquatic taxa
following acute and chronic exposure. This is similar to the predicted hazard from chronic
exposure based on the application of an acute to chronic ratio to acute toxicity endpoint for fish.
ECOSAR modeling is commonly utilized for the environmental risk assessment of new chemical
substances.
After evaluating all available 1-BP test data for data quality, EPA has high confidence in the
results of the acute fish toxicity test as explained in Section 3.1.2, but as data were not available for
other aquatic taxa such as aquatic invertebrates and algae, EPA bolstered the overall dataset using
Structure-Activity Relationship (SAR) predictions for 1-BP provided by ECOSAR (v.2.0) (EPA.
2017). While empirical data are not available to characterize the hazards of 1-BP to aquatic
32 Hazard concern levels for acute exposure: Low >100mg/L; Moderate >1.0 mg/L and <100 mg/L; High <1.0. Hazard
concern levels for chronic exposure: Low >10 mg/L; Moderate >0.1 mg/L and <10 mg/L; High <0.1 (U.S. EPA.
2012e).
Page 182 of 486
-------
invertebrates and algae, ECOSAR modeling is appropriate for 1-BP. ECOSAR-predictions for 1-
BP are based on the neutral organics chemical class. Of the 120 chemical classes within ECOSAR,
this class is the largest and most robust. The dataset used to generate the regression equation to
predict hazards of acute exposure to chemicals within the neutral organics chemical class contains
296 data points for fish, 147 for aquatic invertebrates, and 66 for algae. The dataset used to
generate the regression equation used to predict hazards from chronic exposure contains 46 data
points for fish, 26 for daphnia and 34 for algae. In addition, the majority of the data that comprise
the QSAR training set in the neutral organics chemical class were generated as part of the same
research effort as the high quality acute fish toxicity test for 1-BP (Geiger et al.. 1988). While the
acute toxicity data for 1-BP are not specifically included in the QSAR training set for neutral
organic chemicals in ECOSAR, there are several organic chemicals with a similar log Kow and
molecular weight that are in the training set such as N,N-Dimethylaniline (MW 121, Log KOW=
2.31) and 6-Methyl-5-hepten-2-one (MW=126, LogKOW=2.1) with similar measured toxicity
values for fish that indicate 1-BP is well-characterized by the neutral organics chemical class. As a
result, EPA has medium confidence that the data incorporates the most conservative (highest
toxicity)/environmentally-protective acute and chronic concentrations of concern.
As discussed above, COCs were calculated to provide a conservative estimate for a screening level
comparison with estimated surface water concentrations to identify potential concerns to aquatic
species. The analysis of the environmental COCs are based on EPA methods (U.S. EPA. 2012e).
To calculate acute COCs, the acute 96-hour fish toxicity values were divided by an assessment
factor of 5, while chronic COCs were calculated using an AF of 10. Therefore, based on available
fish data the acute COCs for 1-BP are 13,640 ppb; LCso (67.3 mg/L) / AF of 5 = 13,460 |ig/L or
ppb. To reduce uncertainty resulting from a lack of data, an acute COC of 3,640 ppb was also
calculated based on the most sensitive endpoint predicted by ECOSAR modeling for acute
exposure. Based on estimated chronic hazard endpoint for fish, best available data indicate a
chronic COC of 673 ppb (fish 96-hr LCso (67.3 mg/L) / 10 (ACR) / AF of 10 = 673 |ig/L or ppb.
Similarly to the approach for acute exposure, a chronic COC of 430 ppb was calculated by using
the most sensitive endpoint for chronic exposure as predicted by ECOSAR. These endpoints and
the resulting COC values are presented in Table 3-1. 1-BP is expected to be present at low
concentrations in the terrestrial ecosystems and the sediment compartment of aquatic ecosystems
therefore, no further analysis of hazards to these environmental receptors is necessary.
Page 183 of 486
-------
Table 3-1. Ecological Hazard Characterization of 1-BP
Duration
Test organism
Endpoint
Measured Hazard
value (mg/L)1
Effect
Endpoint
ECOSAR-
predicted
hazard value
(mg/L)2
Acute
Fish
LCso
67.3
Mortality
72.9
Aquatic
invertebrates
ECso
N/A
N/A
42.0
Algae
ECso
N/A
N/A
33.23
Acute COC
13.46
3.32
Chronic
Fish
ChV
6.73
N/A, calculated
with an ACR of
10
7.24
Aquatic
invertebrates
ChV
N/A
N/A
4.263
Algae
ChV
N/A
N/A
8.98
Chronic COC
0.673
0.426
1 Values in the tables are presented as reported bv the studv authors in Geiger et a
.. 1988.
2 Predictions were made with ECOSAR v2.0 (EPA. 2017). More information on the use of this tool
is available at: https://www.epa.gov/tsca-screening-tools/ecological-structure-activity-relationsliips-ecosar-
predictive-model. Model outputs are available in Appendix G.
3 Bolded values indicate the most sensitive species for acute or chronic exposure as indicated by
ECOSAR modeling. These values are used to calculate a COC.
3.2 Human Health Hazard
3.2.1 Background on the Process of Systematic Review
EPA gathered and evaluated information on the human health hazards associated with 1-BP
exposure according to the process described in the Application of Systematic Review in TSCA Risk
Evaluations (U.S. EPA. 2018a). EPA identified hazard data for 1-BP through an extensive
literature search, as described in EPA's Strategy for Conducting Literature Searches for 1-
Bromopropane (1-BP): Supplemental Document to the TSCA Scope Document (U.S. EPA. 2017e).
Published and non-published data sources, including key and supporting studies identified in
previous assessments, were evaluated during this process. EPA also relied heavily on the 2016
Draft Risk Assessment (U.S. EPA. 2016c) to inform hazard characterization. EPA has high
confidence in the toxicological studies used to support risk estimation.
Although EPA conducted a comprehensive search and screening process as described in section
1.5, EPA generally used previous chemical assessments, such as the 2016 Draft Risk Assessment
(U.S. EPA. 2016c). to identify key and supporting information that would be influential in the risk
evaluation, including information supporting key analyses, arguments, and/or conclusions in the
risk evaluation. Where applicable, EPA also considered newer information not considered in the
Page 184 of 486
-------
previous chemical assessments. Using this pragmatic approach, EPA evaluated the quality of the
key and supporting data sources from these authoritative sources (including studies considered for
dose-response analysis and genotoxicity studies considered for contribution to the mode of action
(MOA) analysis) instead of evaluating all the underlying evidence published on the human health
hazards of 1-BP exposure. This allowed EPA to maximize the scientific and analytical efforts of
other regulatory and non-regulatory agencies by accepting for the most part, the scientific
knowledge gathered and analyzed by others. The influential information sources used to support
quantitative analyses represents a smaller pool of studies that were ultimately subjected to the
TSCA systematic review process to ensure that the risk evaluation uses the best available science
in the overall weight of the scientific evidence. Whether data sources were obtained from prior
assessments or more recently published literature, all studies were considered of equal importance
and were evaluated together independent of any previous EPA review.
EPA assessed the quality of the key and supporting studies identified in the 2016 Draft Risk
Assessment (U.S. EPA. 2016c) based on the data quality criteria described in the Application of
Systematic Review in TSCA Risk Evaluations (U.S. EPA. 2018a); these key and supporting studies
were determined to be of high quality {i.e., high confidence). The comprehensive results of the
study evaluations can be found in the Risk Evaluation for 1-Bromopropane (1-BP), Systematic
Review Supplemental File: Data Quality Evaluation of Human Health Hazard Studies. EPA-HQ-
OPPT-2019-0235 (EPA. 2019o). Section 3.2 and Appendix J may also cite other data sources as
part of the reasonably available information on the human health hazards of 1-BP. EPA did not
subject these other data sources to the later phases of the systematic review process {i.e., data
evaluation and integration). Only the key and supporting studies in the 2016 Draft Risk
Assessment for 1-BP (U.S. EPA. 2016c) {e.g., dose-response studies and genotoxicity assays) were
carried forward for dose-response analysis; because these studies were considered to be useful and
relevant for hazard identification, EPA skipped the screening step and entered them directly into
the data evaluation step. Any new studies published since that time, were subjected to the full
TSCA systematic review process.
3,2,2 Approach and Methodology
Development of the 1-BP hazard and dose-response assessment considered principles set forth in
various risk assessment guidance and guidelines issued by the National Research Council and
EPA. Figure 3-1 depicts the process EPA used to evaluate, extract and integrate 1-BP's human
health hazard and dose-response information.
Page 185 of 486
-------
Human Health Hazard Assessment
Risk Characterization
Systematic
Review
Stage
Da [a Evaluation
After fiill-lext screening,
apply pte-detetmined data
quality evaluation criteria
to assess the confidence of
key and supporting studies
ideistified from previous
assessments as well as
new studies not
considered in the previous
assessments
Data
Extraction
Extract data from
key. iiippotliiK:
and new studies
Data Integration
Integrate hazard information by considering quality (i.e.-
strengths* limitations). consistency* relevancy, coherence and
biological plausibility
Humrri ID
Confirm potential
hazards identified
during
scoping'problem
formulation and
identify new hazards
from new literature (if
applicable)
Dose-Response
Analysis
Benchmark dose
modeling: for
endpoints with
adequate data;
Selection of PQDs
tudy Quality
Summary
Table (Hicli.
Medium and
Low)
(Supplemental
File - Appendix
B)
Data
Summaries for
Adverse
Endpoints
(Supplemental
F3e - Appendix.
B)
Summary
Results
WOE
Narrative by
Adverse
Endpoint
(Section 3.2.8)
~¦tpiir of
Systematic
(Sections
i-: i u v.
Risk Cfcaratterizatfou
Analysis
Determine the qualitative
and'or quantitative human
health risks and include, as
appropriate, a discussion of:
» Uncertainty and variability
* Data quality
* PESS
* Alternative interpretations
Risk Estimates
(Sections
4.3.4)
Figure 3-1. EPA Approach to Hazard Identification, Data Integration, and Dose-Response
Analysis for 1-BP
1-BP does not have an existing EPA Integrated Risk Information System (IRIS) Toxicological
Review; however, 1-BP has been the subject of numerous health hazard reviews including the
Agency for Toxic Substances and Disease Registry's (ATSDR's) Toxicological Profile (2017). and
the National Institute for Occupational Safety and Health (NIOSH) Draft Criteria Document
(20161 in addition to the peer-reviewed 2016 Draft Risk Assessment (U.S. EPA. 2016c). During
the analysis phase of the risk evaluation, EPA conducted a systematic review of the available
literature, using these existing assessments as a starting point. Only the references identified as "on
topic" and any new literature published since these existing assessments were considered relevant
data/information sources in this risk evaluation, as described in EPA's Strategy for Conducting
Literature Searches for 1-BP (CASRN106-94-5) Bibliography: Supplemental File for the TSCA
Scope Document, EPA-HQ-OPPT-2016-0741 -0047). These studies were screened against
inclusion criteria in the PECO statement and the studies deemed suitable for dose-response
analysis were further evaluated using the data quality criteria in the Application of Systematic
Review in TSCA Risk Evaluations (U.S. EPA. 2018a).
EPA evaluated the quality of the key and supporting information that would be influential in the
risk evaluation using the data evaluation criteria for human, animal, and in vitro studies described
in the Application of Systematic Review in TSCA Risk Evaluations (U.S. EPA. 2018a). A
summary of the relevant endpoints carried forward for dose-response assessment can be found in
Table 3-2, including the no-observed- or lowest-observed-adverse-effect levels (NOAEL and
LOAEL) for health endpoints by target organ/system, the corresponding benchmark
concentration/dose lower confidence limits (BMCLs/BMDLs), when available, and the
Page 186 of 486
-------
corresponding human equivalent concentrations/doses (HECs/HEDs), and uncertainty factors
(UFs). EPA has not developed data quality criteria for all types of hazard information such as
toxicokinetics and many types of mechanistic data. Despite the lack of formal criteria, for 1-BP,
EPA did review these data informally for quality and used the data to qualitatively support the risk
evaluation. For example, many supplemental studies were considered while investigating the 1-BP
mode of action (MOA). These findings were considered in synthesizing the evidence and
integrated as appropriate, into the relevant health effect sections in Section 3.2.4.
EPA's literature search results for 1-BP human health hazards yielded 813 studies (Section 1.5.1).
This included 14 key and supporting studies that were identified from previous EPA assessments.
Of the 799 new studies screened for relevance, 784 were excluded based on PECO (off topic). The
remaining 15 new studies and 14 key and supporting studies were put through data evaluation; 24
studies were carried forward to data extraction/data integration. Toxicological information was
extracted from studies deemed relevant and suitable for dose response analysis.
For this risk evaluation, all of the known human health hazards of 1-BP were described and
reviewed. Section 3.2.4 (Hazard Identification) discusses the body of studies for relevant health
domains. EPA considered studies of low, medium or high data quality for hazard identification.
Based on this review, EPA narrowed the focus of the 1-BP hazard characterization to liver toxicity,
kidney toxicity, reproductive/developmental toxicity, neurotoxicity, and cancer (brief summaries
are presented for each hazard endpoint in Section 3.2.4; detailed summaries are presented in
Appendix J). The weight of the scientific evidence analysis (Section 3.2.5) included integrating
information from toxicokinetic and toxicodynamic studies for each health domain described in
Section 3.2.4. In particular, data integration considered consistency among the data, data quality,
biological plausibility and relevance (although this was also considered during data screening). For
each health domain, EPA determined whether the body of scientific evidence was adequate to
consider the domain for dose-response modeling. EPA identified or calculated points of departure
(PODs) within each of these health domains.
The POD is used as a starting point for subsequent dose-response (or concentration-response)
extrapolations and analyses. 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 (e.g., benchmark
dose or BMD), a NOAEL value, or a lowest observed adverse effect level (LOAEL) for an
observed incidence, or a change in the level (i.e., severity) of a given response (U.S. EPA. 2002).
PODs were adjusted as appropriate to conform to the specific exposure scenarios evaluated (e.g., to
account for differences in the duration of inhalation exposure between humans and laboratory
animals). Section 3.2.8 provides the dose-response assessment including the selection of PODs for
cancer and non-cancer endpoints and the benchmark dose analysis used in the risk evaluation.
Only the inhalation and dermal routes of exposure were evaluated in this assessment. Insufficient
toxicological data is available via the oral route. In accordance with EPA guidance, the exposure
concentrations used in animal studies were adjusted according to the ratio of the blood:air partition
coefficients, where a default ratio of 1 is applied when the partition coefficient for rats is greater
Page 187 of 486
-------
than that of humans (U.S. EPA. 2002. 1994). For HEC/dermal HED derivations, these exposure
concentrations were further adjusted from the exposure durations used in animal studies to
durations deemed relevant for human exposure scenarios (e.g., 8-hours/day and 5 days/week for
occupational exposures). The majority of exposures occur via inhalation, which is considered the
primary route of exposure; however, the CSAC (Chemical Safety Advisory Committee) Peer
Review of the 2016 Draft Risk Assessment (U.S. EPA. 2016c) recommended that dermal
exposures might be an important contributor to overall exposure and recommended that an
estimate for dermal exposure also be included in the evaluation, with gaps/limitations clearly stated
to address another potential workplace exposure pathway. Since there is limited toxicological data
available by the oral and dermal routes, physiologically based pharmacokinetic/pharmacodynamic
(PBPK/PD) models that would facilitate route-to-route extrapolation have not been identified, and
there are no relevant kinetic or metabolic information for 1-BP that would facilitate development
of dosimetric comparisons, EPA chose to derive dermal HEDs by extrapolating from the inhalation
PODs. The strengths and limitations of this approach are discussed Section 3.2.8.5 and Section 4.3.
EPA followed the recommendations in EPA's Guidelines for Developmental Toxicity Risk
Assessment when making the decision to use developmental toxicity studies to evaluate risks that
may be associated with acute exposure to 1-BP during occupational or consumer use of spray
adhesive, dry cleaning or degreasing products that contain 1-BP. This decision is based on EPA's
assumption that a single exposure during a critical window of fetal development may be sufficient
to produce adverse developmental effects (Guidelines for Developmental Toxicity Risk
Assessment).
3.2.3 Toxicokinetics
This section describes the available information on absorption, distribution, metabolism and
excretion (ADME). For additional details, see Appendix I.
As discussed above in Section 3.2.2, EPA has not published systematic review criteria applicable
to toxicokinetic studies, however all relevant toxicokinetic information was either obtained from
previous regulatory and non-regulatory chemical assessments and/or was informally evaluated for
overall data quality and relevance. Studies in humans and laboratory animals show that 1-BP may
be absorbed following oral, inhalation or dermal exposure; however, dermal and inhalation
pathways are expected to be more relevant for occupational and consumer exposures (Frasch et al..
2011; Hanlev et al.. 2009; NIOSH. 2007; Garner et al.. 2006; Jones and Walsh. 1979). The extent
of absorption via the inhalation route depends on the rate of transfer from pulmonary capillaries to
blood (i.e., blood/air partition coefficient), and the rate of metabolism in various tissue
compartments.
The blood:air partition coefficients calculated for 1-BP in rats (11.7) and humans (7.08) indicate
that it is readily absorbed (Meulenberg and Viiverberg. 2000). Upon uptake, 1-BP distribution via
the systemic circulation follows the individual tissue/blood partition coefficients for respective
tissue compartments. The fat:blood partition coefficient (calculated as the ratio of fat:air and
blood:air partition coefficients) for 1-BP in rats (20) and humans (18) suggests that it may partition
Page 188 of 486
-------
to fat (Meulenberg and Viiverberg. 2000). Higher partitioning to muscle, liver and fat has been
predicted for 1-BP in female versus male rats (ECHA. 2012).
Metabolism studies in rats and mice have shown that 1-BP can directly conjugate with glutathione
forming N-acetyl-S-propyl cysteine, or be oxidized via cytochrome P450 enzymes (primarily
CYP2E1) to reactive metabolites that can be further oxidized and/or conjugated with glutathione
(Jones and Walsh. 1979; Barnslev et al.. 1966) (Figure 3-2). Glutathione conjugates formed via the
glutathione-S-transferase catalyzed pathway are eventually excreted as mercapturic acid
derivatives in urine. Although both pathways remain operative, the CYP2E1 pathway generally
predominates at lower exposure concentrations (Garner et al.. 2006).
1-BP may also be converted to either of two epoxide metabolites, glycidol and propylene oxide
(see Appendix H and Figure 4.1 of IARC (2018)
Further evidence for the specific contribution of CYP2E1 to 1-BP metabolism is provided by
studies with Cyp2e 1" " knockout mice (Garner et al.. 2007) which show the elimination half-life in
these animals to be more than twice that seen in wild type mice (3.2 vs. 1.3 hours, respectively)
following 1-BP inhalation exposure. The ratio of glutathione conjugation to 2-hydroxylation
reactions increased 5-fold in Cyp2el " versus wild-type mice. Earlier work from this laboratory has
shown that administration of 1-aminobenzotriazole (a general suicide inhibitor of P450) caused
nearly complete elimination of 1-BP oxidative metabolism, and a compensatory shift toward GSH
conjugation in rats (Garner et al.. 2006).
In humans and laboratory animals, 1-BP is rapidly eliminated from the body primarily via
exhalation, with lesser amounts excreted in urine and feces (Garner and Yu. 2014; Garner et al..
2006; Ishidao et al.. 2002). In gas uptake studies with male and female rats, the elimination half-
times calculated for 1-BP decreased with increasing air concentrations (Garner and Yu. 2014).
Terminal elimination half-times in male and female mice following 1-BP inhalation exposure at <
800 ppm ranged from 0.5 to 2 hrs (Garner and Yu. 2014; Garner et al.. 2006). (Garner et al.. 2006)
investigated the metabolism of 1-BP in male F344 rats and B6C3F1 mice following inhalation or
tail vein injection and determined that the proportion of 1-BP metabolized via CYP2E1 oxidation
versus glutathione conjugation was inversely proportional to dose in rats, but independent of dose
in mice.
Occupational exposure studies have consistently identified significant correlations between 1-BP
concentrations in ambient air and the levels of 1-BP or its metabolites in urine (Ichihara et al..
2004b; Kawai et al.. 2001). N-acetyl-S-(n-propyl)-L-cysteine (AcPrCys), produced via direct
glutathione conjugation of 1-BP, was the primary urinary metabolite detected in exposed workers
(Hanlev et al.. 2010. 2009; NIOSH. 2007; Valentine et al.. 2007; Hanlev et al.. 2006b).
Page 189 of 486
-------
1-Bromopropane
.Br
h3c^
CYP
alpha-Bromohydrin
H,C
.Glue
Br
1-Bromo-2-hydroxypropane-0-glucuronide
GSH
COOH O
H3C^^^S N ^CH.
H
A/-Acetyl-S-propylcysteine
H3C
1 -Bromo-2-propanol
GSH
COOH O
,Br
Bromoacetone"
GSH
O COOH O
h3c^^S\^n/^ch3
H
A/-Acetyl-S-(2-oxopropyl)cysteine
• CO,
COOH O
if
N CH3
H
A/-Acetyl-3-(propylsulfinyl)alanine
[A/-acetyl-S-propylcysteine-S-oxide]
A/-Acetyl-S-(2-hydroxypropyl)cysteine
CYP
or
FMO
H,C
CYP
or
FMO
COOH O
A,
A/-Acetyl-3-[(2-oxopropyl)sulfinyl]alanine
OH O
,y
COOH O
A
i CH,
OH O COOH O
.JkA
N CH3
H
A/-Acetyl-3-[(2-propenol)sulfinyl]alanine
A/-Acetyl-3-[(2-hydroxypropyl)sulfinyl]alanine
[A/-acetyl-S-(2-hydroxypropyl)cysteine-S-oxide]
Figure 3-2. Metabolism of 1-Bromopropane in Male F-344 Rats and B6C3F1 Mice Following
Inhalation Exposure or Tail Vein Injection*
'Structures in brackets are proposed intermediates and were not isolated in urine.
Page 190 of 486
-------
CYP = cytochrome P450 monooxygenase; FMO = flavin-containing monooxygenase;
GSH = glutathione
Sources: Adapted from (NTP. 2013a; Garner et al.. 2007; Garner et al.. 2006)
3.2.3.1 Biomarkers of Exposure
Several human and laboratory animal studies have investigated the utility of urinary biomarkers of
1-BP exposure (Mathias et al.. 2012; Hanlev et al.. 2009; Valentine et al.. 2007; Hanlev et al..
2006b; B Hymer and Cheever. 2005; Ichihara et al.. 2004a; Kawai et al.. 2001). Bromide ion and
N-acetyl-S-(n-Propyl)-L-Cysteine (AcPrCys) have shown the most promise as biomarkers of
exposure to occupationally-relevant concentrations.
1-BP is metabolized rapidly, via glutathione conjugation and cytochrome P-450 mediated
oxidation, producing many metabolites which are subsequently excreted in urine. Glutathione
conjugation leads to bromide ion release and formation of mercapturic acid derivatives. Bromide
ion levels have been used as an internal biomarker of 1-BP exposure. They are slowly excreted
from the body; the elimination half-life of bromide ions in blood generally ranges from 10.5 to
14 days (Mathias et al.. 2012; Hanlev et al.. 2006b). N-acetyl-S-(n-propyl)-L-cysteine (AcPrCys) is
the primary urinary metabolite found in 1-BP exposed workers (see below); it also is considered to
be a valid biomarker for 1-BP exposure (Mathias et al.. 2012; Valentine et al.. 2007).
Both Kawai (2001) and Ichihara (2004a) have shown a correlation between urinary 1-BP levels
and 1-BP occupational exposure; however, the degree of correlation varied between studies. Kawai
et al. (2001) reported a correlation coefficient of 0.9 for 1-BP concentrations in air and urine; the
highest 1-BP concentration in air was 27.8 ppm (geometric mean = 1.42 ppm). Ichihara et al.
(2004a) also reported a statistically significant correlation between 1-BP air concentrations and
urinary levels measured on the same day (r2 = 0.39; p < 0.05). NIOSH has suggested that urinary
1-BP levels may be a more suitable biomarker than urinary bromide concentrations; however, to
ensure accuracy, samples must be tested immediately after collection using gas chromatography -
mass spectrometry, which may be unfeasible or cost prohibitive (NIOSH. 2003a).
Both urine and serum bromide ion levels have been used as biomarkers of 1-BP exposure in
workers. Toraason et al. (2006) found a high correlation (p < 0.0001) between 1-BP exposure and
bromide ion concentrations in serum (r2= 0.7 to 0.8), and urine (r2= 0.6 to 0.9) when evaluating
personal breathing zone samples from approximately 50 workers. Workplace exposures ranged
from 0.2 to 270 ppm (TWA), and the correlation coefficient for 1-BP air levels and urinary
bromide levels was 0.5. Using gas chromatography with electron capture detection to evaluate
samples taken from Japanese workers (n=33) following 1-BP exposure during an 8-hour shift of
cleaning and painting, (Kawai et al.. 2001) reported a good correlation (r2= 0.5) between bromide
levels in urine and 1-BP levels in air; however, control subjects exhibited high background levels
of urinary bromide, which were subsequently linked to dietary exposure (Zhang et al.. 2001).
Hanley et al. (2006b) reported 30 workers who were exposed to 1-BP spray adhesives to make
polyurethane foam seat cushions. Personal breathing zone samples indicated a geometric mean
exposure of 92 ppm (range = 45-200 ppm) for sprayers and 11 ppm for workers in other parts of
Page 191 of 486
-------
the plant. The composite (48-hour) urinary bromide concentrations for sprayers (n=12) ranged
from 119 to 250 mg/g creatinine and for non-sprayers (n=17) ranged from 5.5 to 149 mg/g
creatinine. The composite bromide concentration in unexposed control subjects (n=7) ranged from
2.6 to 5.9 mg/g creatinine. Daily bromide excretion was approximately four times greater for
sprayers than non-sprayers. Based on these results, urinary bromide concentration appears to be a
useful index of 1-BP exposure.
Given the confounding factors identified (Kawai et al.. 2001). a search for biomarkers of 1-BP
exposure that are not influenced by dietary (or other non-occupational exposures) was initiated.
Valentine et al. (2007). Mathias et al. (2012) and Hanley et al. (2009) demonstrated that the
mercapturic acid derivative, AcPrCys, could be used as a urinary biomarker of 1-BP exposure.
Both the availability of sensitive methods with an acceptable limit of detection (LOD) for this
metabolite, and its demonstrated persistence in urine suggest that it may serve as a reliable
biomarker of exposure. In addition, 1-BP volatility and rapid elimination in exhaled breath
suggests that the measurement of mercapturic acid derivatives in urine may be preferable to 1-BP
measurements. Valentine et al. (2007) sampled blood and urine from women in a 1-BP production
facility in China (Ichihara et al.. 2004b). A significant increase in AcPrCys adducts on human
globin was demonstrated using LC/MS/MS to evaluate samples taken from 26 1-BP exposed
workers and 32 non-exposed controls. Worker exposures ranged from 0.34 ppm to 49.2 ppm, and
urinary AcPrCys levels analyzed using GC/MS, increased with increasing 1-BP exposure (n=47)
(Toraason et al.. 2006). Hanley et al. (2009) used aliquots from the urine specimens from those
same workers who were exposed to 1-BP spray adhesives (Hanley et al.. 2006a) who applied spray
adhesives to foam cushions as described above, to determine the utility of AcPrCys as a biomarker
for 1-BP exposure. Higher levels of urinary AcPrCys were observed in sprayers than non-sprayers
(geometric mean was approximately four times higher in sprayers). AcPrCys and bromide levels
were highly correlated (p < 0.0001) in the same urine samples, and both showed statistically
significant Spearman's correlation coefficients based on 1-BP TWA exposure concentrations.
Mathias et al. (2012) evaluated the same cohort of workers, reporting the results of Hanley et al.
(2009) and 3-bromopropionic acid (3-BPA), which was evaluated for its potential to induce
mutagenic effects and tumor formation in toxicological studies. When urine samples were analyzed
for 3-BPA, it was not detected in 50 samples (LOD = 0.01 |ig/mL). In a study of workers exposed
to 1-BP based vapor degreasing solvent, Hanley et al. (2010) found AcPrCys in urine analyses
were sensitive enough to measure exposure from these workers with much lower air exposures and
AcPrCys was statistically associated with 1-BP TWAs.
At the time of the CSAC Peer Review for the 2016 Draft Risk Assessment (U.S. EPA. 2016c).
NHANES data was released on selected urinary metabolites of VOCs, primarily associated with
tobacco smoking. Although it is not associated with smoking, AcPrCys (or BPMA) was included
in the list of 28 VOC metabolites based on its similarity in chemistry to the other tobacco
metabolites. NHANES data indicated that BPMA was detected in urine samples of children and
adults from NHANES 2005-2006, 2011-2012, and 2013-2014 at approximately 3-4 ug/L
(geometric mean) (CDC. 2019). Several papers describing the summary statistics of the exposures
were published at this time, with one reporting a 99% detection of BPMA in 488 pregnant women
in the National Childrens Study (2.6 ng/mL, 50th percentile) ((Boyle et al.. 2016; Jain. 2015; Alwis
Page 192 of 486
-------
et al.. 2012)). These data were discussed during the CSAC Peer Review and the reviewers stated
that. .the measurement of BPMA levels by Boyle et al. (2016) suggests the possibility of low
level, but very widespread, non-occupational exposures to 1-BP; however, the Committee
recognizes that there are some questions regarding the specificity of the biomarker used." The
literature does not contain any additional information on the specificity of this biomarker since the
last peer review. In addition, CDC has no further information on this biomarker. Therefore, it can
still be assumed that the specificity of N-acetyl-S-(n-propyl)-L-cysteine as a biomarker for the U.S.
population is questionable (ATSDR. 2017) and not informative for use in dose-response analysis.
3.2.3.2 PBPK Models
A PBPK model for 1-BP in rats was developed by (Garner et al.. 2015). The model simulates 1-BP
exposures via inhalation wherein distribution of 1-BP to tissues is assumed to be flow-limited.
Metabolism of 1-BP was simulated with Michaelis-Menten kinetics for oxidative metabolism by
cytochrome P450 and first order kinetics for GSH conjugation; parameters were fit to the time
course data of chamber concentrations for 1-BP used in rat inhalation studies. Additional metabolic
parameters were fit to time course data of chamber concentrations of 1-BP for rat inhalation studies
when female rats were pretreated with either the cytochrome P450 inhibitor 1-aminobenzotriazole
(ABT) or the GSH synthesis inhibitor D,L-buthionine (S,R)-sulfoximine (BSO). These results
show the relative contributions of oxidative metabolism via cytochrome P450 and conjugation with
GSH in female rats. Confidence in the PBPK model predictions for 1-BP concentrations in blood
and tissues are limited by the lack of comparison of model predictions with measured data. The
PBPK model was further extended to simulate human exposures by scaling the physiological
parameters to humans, assuming the partition coefficients are the same in rats and humans and
scaling metabolic parameters by BW3/4. Cross species and route to route extrapolations with the
Garner et al. (2015) model are precluded by the lack of data to inform a model of a species other
than rat and a route other than inhalation.
3.2.4 Hazard Identification
This section summarizes the available cancer and non-cancer hazard information for 1-BP. A
comprehensive summary table (Table Apx J-2) which includes all endpoints considered for this
assessment, as well as detailed summaries for each health effect domain, are presented in Appendix
J. The 1-BP database includes epidemiological studies, experimental animal studies, and in vitro
studies. Human studies (case-control studies, industrial surveys, and case reports) corroborate that
the nervous system is a sensitive target of 1-BP exposure in humans. Certain characteristics of the
evaluation of 1-BP human studies are discussed throughout this section. Experimental animal
studies of 1-BP consist of studies that evaluated liver toxicity, kidney toxicity, immunotoxicity,
reproductive toxicity, developmental toxicity, neurotoxicity, genetic toxicity, and carcinogenicity.
The following sections also describe several in vitro and some animal studies that evaluated
biochemical and other endpoints used to consider the evidence related to modes of action.
Page 193 of 486
-------
EPA considered many of the studies as informative and useful for characterizing the health hazards
associated with exposure to 1-BP. EPA extracted the results of key and supporting studies from the
Mitt Risk Assessment (U.S. EPA. 2016c) and studies identified in the updated literature
search.
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 (U.S. EPA. 2018a). The results of the data quality evaluation for the non-cancer
studies (key and supporting studies and new studies) are described in Section 3.2.4.1 and included
in the data extraction summary tables in the supplementary files accompanying this document. As
a result, EPA narrowed the focus of this assessment to six adverse health effect domains: (1) liver
toxicity, (2) kidney toxicity, (3) reproductive toxicity, (4) developmental toxicity, (5) neurotoxicity,
and (6) carcinogenicity. For non-cancer endpoints, emphasis was placed on acute/shortterm
inhalation, and repeated-dose inhalation studies identified as most appropriate for hazard
characterization and dose-response analysis.
The weight of the scientific evidence Section 3.2.5 identifies any study evaluation concerns that
may have meaningfully influenced the reliability or interpretation of the results. Studies with high
confidence for hazard identification and considered for dose-response assessment are discussed in
Section 3.2.8 and included in Table 3-2.
3.2.4.1 Non-Cancer Hazard Identification
Toxicity Following Acute Exposure
Studies in animals following acute exposures are limited to acute lethality studies only. In animals,
deaths from acute inhalation exposure to 1-BP occurred only at high exposure concentrations. LCso
values in rats ranged from 7,000 to 14,374 ppm for 4-hour inhalation exposure (Kim et al.. 1999a;
Elf Atochem. 1997). Deaths were associated with an acute inflammatory response and alveolar
edema (Elf Atochem. 1997). Similarly, for oral exposure, the LD50 was >2,000 mg/kg (Elf
Atochem. 1993a). No information on 1-BP toxicity following acute exposure in humans was
located.
Liver Toxicity
Data from animal studies suggest the liver is a target for 1-BP. Reported effects include liver
histopathology (e.g., hepatocellular vacuolation, swelling, degeneration and necrosis), increased
liver weight, and clinical chemistry changes indicative of hepatotoxicity (Wang et al.. 2012; NTP.
2011a; Liu et al.. 2009; Lee et al.. 2007; Yamada et al.. 2003; WIL Research. 2001; Kim et al..
1999a; Kimetal.. 1999b; ClinTrials. 1997a. b).
Hepatotoxicity was not directly evaluated in any of the human studies identified in the literature;
however, one study evaluated liver function indirectly in a cohort of 86 Chinese workers exposed
to 1-BP (median exposure levels up to 22.6 ppm) for an average of approximately 40 months (Li et
al.. 2010) and no statistically significant clinical chemistry changes indicative of liver damage were
observed.
Page 194 of 486
-------
Kidney Toxicity
Laboratory animal studies have provided evidence of renal toxicity following 1-BP exposure.
Reported kidney effects include increased organ weight, histopathology (pelvic mineralization,
tubular casts) and associated clinical chemistry changes (e.g., increased blood urea nitrogen) (NTP.
2011a; Yamada et al.. 2003; WIL Research. 2001; Kim et al.. 1999a; ClinTrials. 1997a. b).
No studies that directly evaluated 1-BP induced renal effects in humans were identified in the
published literature; however, no significant clinical chemistry changes indicative of kidney
damage were observed in a cohort of 86 Chinese workers exposed to 1-BP (median exposure levels
up to 22.58 ppm) for an average of approximately 40 months (Li et al.. 2010) or in 45 workers
exposed to a geometric mean concentration of 81.2 ppm for an average of 29 months (NIOSH.
2003a).
Immunotoxicity
There is limited evidence for immune effects of 1-BP in animal studies. Two independent studies
of immune function showed that 1-BP can suppress immune responses in rodents (Anderson et al..
2013; Lee et al.. 2007). Anderson et al. (2010) reported a decreased IgM plaque-forming response
to immunization with sheep red blood cells (sRBC ) in splenocytes harvested from female rats and
mice following subchronic inhalation exposure to 1-BP (NOAEL = 500 ppm in rats; LOAEL [no
NOAEL identified] = 125 ppm in mice). Associated effects in both species included decreases in T
cells and increases in natural killer cells in the spleen; other effects reported in mice include
reduced splenic cellularity and decreased absolute spleen weight. (Lee et al.. 2007) also reported a
decreased antibody response to sRBC and reduced splenic cellularity in female mice after a single
oral dose of 1-BP (LOAEL [no NOAEL identified] = 200 mg/kg). Investigation of immune
endpoints in other studies (limited to organ weights and histopathology of spleen, thymus, and
other lymphoreticular tissues) showed no effects at concentrations as high as 1000 ppm in rats and
500 ppm in mice following subchronic inhalation exposure, and 500 ppm in rats and 250 ppm in
mice following chronic inhalation exposure (NTP. 2011a; Yamada et al.. 2003; WIL Research.
2001; Ichihara et al.. 2000a; Kim et al.. 1999b; ClinTrials. 1997a. b). No information regarding 1-
BP immunotoxicity in humans was located.
Reproductive Toxicity
Animal studies suggest that the reproductive system is a target of concern for 1-BP exposure. A
two-generation reproduction inhalation (via whole-body exposure) study in rats reported adverse
effects on male and female reproductive parameters (WIL Research. 2001). The majority of these
effects exhibited a dose-response beginning at 250 ppm, with statistical significance observed at
500 ppm. Significant increases in the number of 'former' or 'unaccounted' implantation sites (i.e.,
the difference between the total number of implantation sites counted and the number of pups
born) were reported by (WIL Research. 2001). EPA considers this finding to be indicative of post-
implantation loss (pre-implantation loss could not be determined because of a lack of data on the
number of primordial follicles at 100, 250 and 500 ppm). Fo females experienced a 48% reduction
in fertility at 500 ppm and complete infertility at 750 ppm. Other effects reported in this study
include dose-related decreases in mating indices, increased estrous cycle length, and a significant
Page 195 of 486
-------
trend of increasing numbers of Fo females with evidence of mating without delivery (a Cochran
Armitage trend test conducted by EPA calculated a p-value <0.0001).
Statistically significant changes in reproductive endpoints in Fo males include decreased absolute
prostate and epididymal weights at exposures > 250 and 500 ppm respectively, as well as
decreased sperm motility, and decreased mating (500 ppm) and fertility indices (750 ppm) (WIL
Research. 2001). The findings described above are supported by similar reports of reproductive
toxicity from independent laboratory studies with rats and mice, including spermatogenic effects
(decreased sperm count, altered sperm morphology and decreased sperm motility) and organ
weight changes in males (decreased epididymis, prostate and seminal vesicle weights) as well as
estrous cycle alterations and decreased numbers of antral follicles in females (NTP. 2011a; Qin et
al.. 2010; Liu et al.. 2009; Yu et al.. 2008; Banu et al.. 2007; Yamada et al.. 2003; WIL Research.
2001; Ichihara et al.. 2000b).
No data were located on the reproductive effects of 1-BP exposure in humans.
Developmental Toxicity
The developmental effects of 1-BP exposure have been evaluated on the basis of standard prenatal
developmental toxicity studies, and a two-generation reproductive toxicity study in rats exposed
via whole-body inhalation. No standard developmental neurotoxicity studies are available.
Evidence supporting fetal development as a sensitive target of 1-BP exposure is provided by a
number of laboratory animal studies. The current database consists of developmental toxicity
testing that shows severe effects resulting from prenatal exposure during gestation and postnatal
exposure studies showing adverse developmental effects that manifest at various stages of
development, and span multiple generations (WIL Research. 2001). Reported adverse
developmental effects following 1-BP exposure include dose-related decreases in live litter size
(WIL Research. 2001). postnatal survival (Furuhashi et al.. 2006). and pup body weight, brain
weight and skeletal development (Huntingdon Life Sciences. 1999). (Huntingdon Life Sciences.
2001); (WIL Research. 2001). (WIL Research. 2001) also reported decreases in the number of
implantation sites, and increases in 'unaccounted' implants for corresponding ovulatory events,
reported as the difference between the total number of implantation sites counted and the number
of pups born. Additional qualitative evidence of impaired development is provided by results from
dominant lethal assays with 1-BP which show increased implantation loss (at week 8) in rats
subjected to five days of oral 1-BP exposure at 400 mg/kg (Saito-Suzuki et al.. 1982) and in mice
(at week 5) following 1-BP exposure via gavage administration at 600 mg/kg for ten days prior to
mating (Yu et al.. 2008).
No data were located on the developmental effects of 1-BP exposure in humans.
Neurotoxicity
Data from studies in humans and animals demonstrate that the nervous system is a sensitive target
of 1-BP exposure. Both the central and peripheral nervous systems are affected. In animal
inhalation studies, the degree or severity of neurotoxicity produced by 1-BP depends on the
Page 196 of 486
-------
concentration as well as duration of exposure, with lower concentrations being effective at longer
exposures. Most inhalation studies using concentrations of >1000 ppm reported ataxia progressing
to severely altered gait, hindlimb weakness to loss of hindlimb control, convulsions, and death
(e.g., (Banu et al.. 2007; Ishidao et al.. 2002; Yu et al.. 2001; Fueta et al.. 2000; Ichihara et al..
2000a; Ohnishi et al.. 1999; ClinTrials. 1997a. b). Concentrations of 400-1000 ppm produced
neuropathological changes including peripheral nerve degeneration, myelin sheath abnormalities,
and spinal cord axonal swelling (Wang et al.. 2002; Yu et al.. 2001; Ichihara et al.. 2000a). Brain
pathology has also been reported in several studies, including white and gray matter vacuolization,
degeneration of Purkinje cells in the cerebellum and decreased noradrenergic but not serotonergic
axonal density in frontal cortex and amygdala at exposures >400 ppm (Mohideen et al.. 2013;
Mohideen et al.. 2011; Ohnishi et al.. 1999; ClinTrials. 1997a. b). Decreased brain weight has been
reported in adult and developmental studies (Subramanian et al.. 2012; Wang et al.. 2003; WIL
Research. 2001; Ichihara et al.. 2000a; Kim et al.. 1999a; ClinTrials. 1997b). In a two-generation
study (WIL Research. 2001). the NOAEL for decreased brain weight in F1-generation males was
100 ppm (BMD modeling did not produce an acceptable fit); this value is brought forward for risk
assessment representing neuropathological changes.
Physiological, behavioral, and biochemical measures have been used to characterize and develop
dose-response data for neurological effects. Motor nerve conduction velocity and latency measured
in the rat tail nerve were altered at concentrations > 800 ppm with progressive changes from 4 to
12 weeks of exposure (Yu et al.. 2001; Ichihara et al.. 2000a). In the brain, electrophysiological
changes in hippocampal slices were seen at concentrations of 400 ppm and above (Fueta et al..
2002a; Fueta et al.. 2002b; Fueta et al.. 2000); Fueta et al.. 2004; Fueta et al.. 2007; Ueno et al..
2007). Behavioral tests such as hindlimb grip strength, landing foot splay, traction (hang) time, gait
assessment, motor activity, and water maze performance provide dose-response data and tend to be
more sensitive than neuropathology or physiological changes, with effects at concentrations as low
as 50-200 ppm (Banu et al.. 2007; Honma et al.. 2003; Ichihara et al.. 2000a). Exposures to
concentrations > 50 ppm produce changes in neurotransmitters, biomarkers, and proteome
expressions suggesting alterations in the function and maintenance of neural and astrocytic cell
populations (Huang et al.. 2015; Mohideen et al.. 2013; Zhang et al.. 2013; Huang et al.. 2012;
Subramanian et al.. 2012; Huang et al.. 2011; Mohideen et al.. 2009; Suda et al.. 2008; Yoshida et
al.. 2007; Wang et al.. 2003; Wang et al.. 2002). Although less extensively tested, oral or
subcutaneous dosing of 1-BP resulted in similar findings as for inhalation exposure, with effects at
>200 mg/kg-day (Guo et al.. 2015; Zhong et al.. 2013; Wang et al.. 2012; Zhao et al.. 1999).
Neurological endpoints selected for dose-response analysis were datasets for decreased time
hanging from a suspended bar (traction time) in rats in a 3 -week inhalation study (Honma et al..
2003) and decreased hind limb grip strength in rats in a 12 -week inhalation study (Ichihara et al..
2000a). These functional measures are relevant to peripheral neurotoxicity reported in human
studies.
Human studies (case-control studies, industrial surveys, and case reports) corroborate that the
nervous system is a sensitive target of 1-BP exposure in humans. Clinical signs of neurotoxicity
(including headache, dizziness, weakness, numbness in lower extremities, ataxia, paresthesia, and
changes in mood) and motor and sensory impairments were noted in the case reports of workers
Page 197 of 486
-------
occupationally exposed to 1-BP for 2 weeks to 3 years at estimated concentrations exceeding
averages of 100 ppm (Samukawa et al.. 2012; Maiersik et al.. 2007; Raymond and Ford. 2007;
Ichihara et al.. 2002; Sclar. 1999). and in industrial surveys with average exposures greater than 81
ppm (ranging from 2 weeks to 9 years) (NIOSH. 2003a. 2002a. c). Cross-sectional studies of
Chinese workers reported increased distal latency and decreased sural nerve conduction velocity in
female workers. Statistically significant decreased vibration sense in toes was observed across all
exposure groups (0.07-106.4 ppm) compared to controls (EPA. 2019e; Li et al.. 2010; Ichihara et
al.. 2004b). There were several methodological limitations in these studies, discussed in depth in
Appendix J.4; however, these studies provide evidence of neurotoxicity in workers exposed to 1-
BP.
3.2.4.2 Genotoxicity and Cancer Hazards: Weight of the Scientific Evidence
Integration and Mode of Action
Genetic Toxicity
Barber (1981) and BioReliance (2015) both performed bacterial reverse mutation studies of 1-BP
using test systems characterized as 'closed', but yielded different results for mutagenicity. In the
study by Barber (1981). a positive mutagenicity result was observed for 1-BP in Salmonella
typhimurium strains TA 1535 and TA 100 (but not TA 1537, TA 1538, or TA 98) in the presence
and absence of metabolic activation. In contrast, the study by BioReliance (2015) found no
evidence of mutagenicity in S. typhimurium strains TA 98, TA 100, TA 1535, and TA 1537 or
Escherichia coli strain WP2 uvrA (a DNA repair-deficient strain) in the presence or absence of
metabolic activation. The major differences in experimental design between the two studies are the
method of test substance application (vapor exposure of plated bacteria versus aqueous
preincubation exposure) and the methods used to achieve a 'closed' system to account for the
inherent volatility of 1-BP (fully enclosed test chamber versus preparation of solutions in screw-
capped tubes). It is therefore likely the varied mutagenicity results from the two studies {i.e.,
positive results in the Barber (1981) study and negative results in the BioReliance (2015) study)
are due to differences in the methods used for exposure and to compensate for the volatility of 1-
BP in the bacterial reverse mutation assay. This assumption is supported by the fact that in the
BioReliance (2015) study, analytical concentrations of 1-BP in preincubation tubes during the
confirmatory assays were far below target, with 4-37% of target concentrations at the beginning of
the preincubation period and 2-5% of target concentrations by the end of the preincubation period
(see Appendix J.5.6 for more details). Other tests for mutagenicity in bacteria were negative (NTP.
2011a; Kim et al.. 1998). While these tests may not have been conducted in closed systems, the
occurrence of cytotoxicity at high concentrations in the (NTP. 2011a; Kim et al.. 1998) study
suggests that sufficient quantities of 1-BP were present to induce that effect, and therefore, that the
lack of observed mutagenicity in the study did not result from lack of 1-BP in the test medium, but
rather from lack of mutagenic activity of 1-BP.
In mammalian cells tested in vitro, increased mutation frequency was observed in mouse
lymphoma cells exposed to 1-BP with or without activation (Elf Atochem. 1996a). Using the
comet assay, (Toraason et al.. 2006) found evidence of DNA damage in human leukocytes exposed
Page 198 of 486
-------
to 1-BP in vitro, but only equivocal evidence of damage in leukocytes from workers exposed to 1-
BP on the job. Tests conducted in vivo were mostly negative, including assays for dominant lethal
mutations and micronuclei induction in rats and mice (NTP. 2011a; Yu et al.. 2008; Kim et al..
1998; Elf Atochem. 1995; Saito-Suzuki et al.. 1982). Negative results were found for mutagenicity
in inhalation studies in the Big Blue® mouse model (Stellies et al.. 2019); (Young. 2016); while
these results do not support a mutagenic mode of action (MMOA), they also do not provide
sufficient evidence against mutagenicity of 1-BP based on several conceptual, methodological, and
study comprehensiveness uncertainties (see Appendix J.5.6).
DNA binding studies have shown that 1-BP can produce N7-propyl guanine adducts in calf thymus
DNA in vitro and in multiple tissues in rats treated in vivo, that the degree of adduct formation
increases with dose of 1-BP, and that metabolic activation is not needed for adduct formation in
vitro (Thapa et al.. 2016) (Nepal et al.. 2019). However, these specific DNA adducts are not known
to lead to mutations.
Positive results have been observed in several genotoxicity tests using known or postulated
metabolites of 1-BP (including glycidol, propylene oxide, a-bromohydrin, 3-bromo-l-propanol,
and l-bromo-2-propanol) (NTP. 2014; IARC. 2000. 1994). Epoxide intermediates such as
propylene oxide and glycidol are expected to have more mutagenic activity than 1-BP (IARC.
2018. 2000. 1994).
Carcinogenicity
Evidence from chronic cancer bioassays in rats and mice suggests that 1-BP may pose a
carcinogenic hazard to humans. Significant increases in the incidence of skin tumors
(keratoacanthoma/squamous cell carcinomas) in male F344 rats, rare large intestine adenomas in
female F344 rats, and alveolar/bronchiolar adenomas or carcinomas (combined) in female B6C3F1
mice were observed following exposure to 1-BP via inhalation for two years (NTP. 2011a). NTP
concluded that these data show some evidence for carcinogenicity in male rats, clear evidence for
carcinogenicity in female rats, no evidence for carcinogenicity in male mice, and clear evidence for
carcinogenicity in female mice. No other laboratory animal or human data were located on the
carcinogenicity of 1-BP. IARC (2018) concluded that 1-BP "ispossibly carcinogenic to humans
(Group 2Bf based on inadequate evidence in humans and sufficient evidence in experimental
animals for the carcinogenicity of 1-BP, noting there is: (a) strong evidence that 1-BP is
electrophilic or can be metabolically activated to reactive intermediates; (b) strong evidence that 1-
BP induces oxidative stress, induces chronic inflammation, and is immunosuppressive; and (c)
moderate evidence that 1-BP modulates receptor-mediated effects and is genotoxic. By the criteria
presented in EPA's Guidelines for Carcinogen Risk Assessment (U.S. EPA. 2005a). 1-BP may be
considered "Likely to be Carcinogenic in Humans" based on the positive findings for
carcinogenicity in more than one test species together with positive findings for the direct
reactivity of 1-BP with DNA and suggestive but inconclusive evidence for genetic toxicity.
As noted above, 1-BP has been shown to be a multi-site carcinogen in rats and mice. The mode of
action for 1-BP carcinogenesis has not been established; however, there is data supporting a
mutagenic mode of action (MMOA):
Page 199 of 486
-------
a. Ames test: 1-BP was mutagenic with and without metabolic activation in the Ames
Salmonella assay in one (Barber,(1981) of two studies when testing was conducted in
closed systems designed for testing volatile chemicals.
b. Mammalian cells and tissues: 1-BP caused mutations in cultured mammalian cells with or
without metabolic activation in one study (Elf Atochem. 1996a) and DNA damage in
human leukocytes exposed in vitro without metabolic activation in another study (Toraason
et al.. 2006).
c. Evidence was equivocal, however, for DNA damage in leukocytes collected from workers
exposed to 1-BP on the job (Toraason et al.. 2006).
d. Metabolic activation to mutagenic intermediates: Rodent metabolic studies have indicated
that 1-BP can be activated by CYP2E1 to at least five different mutagenic intermediates
(NTP. 2014: I ARC. 2000. 1994). including two clearly mutagenic and carcinogenic
chemicals (glycidol and propylene oxide) IARC (2018). which are listed in the NTP Report
on Carcinogens as "reasonably anticipated to be human carcinogens" (2013a). Glycidol has
been shown to induce tumors in the intestines (NTP. 1990). one of the carcinogenic targets
of 1-BP. Propylene oxide inhalation has been shown to induce tumors at multiple sites
including the thyroid, adrenal gland, and mammary gland (IARC. 1994). The available
evidence suggests similar metabolic pathways for 1-BP in humans and rodents. The role of
epoxides as proximate carcinogens should be explored with regard to the mode of 1-BP
carcinogenicity.
e. Structure-Activity Relationship (SAR) consideration: SAR may be used as a criterion for
consideration in EPA's Guidelines for Carcinogen Risk Assessment (U.S. EPA. 2005a).
From the SAR point of view, 1-BP is a low molecular weight alkyl bromide that is
electrophilic (IARC. 2018: NTP. 2013a) and generally known to possess alkylating
potential (1-BP has been shown to bind to DNA in vitro and in vivo, although the specific
adducts that have been found, N7-propyl guanine adducts, are not known to lead to
mutations). Bromoethane and 1-bromobutane, two analogs of 1-BP, both produced positive
results in the Ames assay when tested in closed systems. Bromoethane is a known
carcinogen via the inhalation route of exposure (NTP. 1989a). whereas 1-bromobutane has
not been tested for carcinogenic activity.
In contrast, other lines of evidence do not provide clear support for a MMOA for 1-BP
carcinogenicity including:
a. With the exception of the one closed study noted above, results are negative for 1-BP in the
Ames assay (NTP. 2011a: Kim et al.. 1998). including in the other closed study
(BioReliance. 2015).
b. While the high volatility of 1-BP is a complication for tests conducted using open systems,
at least one of the negative open studies (NTP. 2011) observed cytotoxicity at high 1-BP
concentrations, indicating the presence of 1-BP in the test medium and consequently
suggesting that this was a valid test of 1-BP mutagenicity.
c. In vivo micronucleus assays in bone marrow and circulating erythrocytes of mice and rats
were negative, as were dominant lethal assays in mice and rats (NTP. 2011a: Yu et al..
2008: Kim et al.. 1998: Elf Atochem. 1995: Saito-Suzuki etal.. 1982).
Page 200 of 486
-------
d. As with other types of genotoxicity data, it is uncertain how predictive the results of in vivo
micronucleus assays are for carcinogenicity; Benigni (2012) found a low correlation
between in vivo micronucleus assay results and carcinogenicity.
e. 1-BP did not induce mutations at the ell gene of female B6C3F1 transgenic Big Blue®
mice following whole-body inhalation exposure to 1-BP vapor concentrations of 62.5, 125,
or 250 ppm for 5 days/week (Stellies et al.. 2019; Weinberg. 2016) or 7 days/week over a
28-day period (Young. 2016). These studies do not provide definitive evidence against a
MMOA, however, due to limitations in test design, as discussed in Appendix J.5.8.
f. Other possible MO As: NTP (2013 a) suggested that in addition to mutagenicity, at least
three other mechanisms, including oxidative stress, immunosuppression, and cell
proliferation can contribute to the multi-stage process of carcinogenesis for 1-BP.
Following EPA's Guidelines for Carcinogen Risk Assessment (U.S. EPA. 2005a). the evidence for
a MMOA for 1-BP induced carcinogenicity is suggestive but inconclusive. Given the lack of a
clearly defined MOA or information on the shape of the dose-response curve in the low dose
region, linear extrapolation from the point of departure is recommended per EPA's Guidelines for
Carcinogen Risk Assessment (U.S. EPA. 2005a).
3.2.5 Evidence Integration and Evaluation of Human Health Hazards
This section integrates and evaluates both the non-cancer and cancer human health hazard
endpoints from the health hazard domains discussed in Section 3.2.4. This evidence integration and
evaluation uses a weight of the scientific evidence approach wherein the strengths, limitations and
relevance of the hazard data were analyzed and summarized across studies, taking into
consideration consistency and coherence among animal studies, quality of the studies (such as
whether studies exhibited design flaws that made them unacceptable) and biological plausibility.
Relevance of data was considered primarily during the screening process but may also have been
considered when weighing the scientific evidence.
The best available human health hazard information was selected for benchmark dose modeling
based on an integration of the data quality evaluation results, MOA information and overall weight
of scientific evidence. Based on this approach, liver toxicity, kidney toxicity, reproductive toxicity,
developmental toxicity, and neurotoxicity are the primary (non-cancer) health effects associated
with 1-BP exposure. Emphasis on acute/shortterm inhalation, and repeated-dose inhalation studies
were considered most appropriate for hazard characterization and dose-response analysis.
3.2.5.1 Weight of the Scientific Evidence for Liver Toxicity
Hepatic effects, including increases in liver weight, liver histopathology and associated clinical
chemistry changes, were widely reported in animal studies of 1-BP (Wang et al.. 2012; NTP.
2011a; Liu et al.. 2009; Lee et al.. 2007; Yamada et al.. 2003; WIL Research. 2001; Kim et al..
1999a; Kim et al.. 1999b; ClinTrials. 1997a. b). Human data were available from a single study (Li
et al.. 2010) that found no clinical chemistry changes indicative of liver toxicity. Overall, based on
limited human evidence and evidence in multiple animal species from highly rated studies, there is
Page 201 of 486
-------
evidence to support non-cancer liver effects following 1-BP exposure. Therefore, this hazard
endpoint was carried forward for dose-response analysis.
3.2.5.2 Weight of the Scientific Evidence for Kidney Toxicity
Several animal studies of 1-BP reported effects on the kidneys, including increases in kidney
weight, renal histopathology and associated clinical chemistry changes (NTP. 2011a; Yamada et
al.. 2003; WIL Research. 2001; Kim et al.. 1999a; ClinTrials. 1997a. b). Human data were limited
to two studies of workers that showed no clinical chemistry changes indicative of renal toxicity (Li
et al.. 2010; NIOSH. 2003a). Overall, the evidence from high-quality animal studies supports
kidney toxicity as a consequence of 1-BP exposure, and this hazard endpoint was carried forward
for dose-response analysis.
3.2.5.3 Weight of the Scientific Evidence for Immunotoxicity
Two studies were located that found functional evidence of immunosuppressive effects of 1-BP in
animals, with corresponding decreases in splenic cellularity and spleen weight (Anderson et al..
2013; Lee et al.. 2007). Other animal studies did not evaluate immune function but found no
effects on spleen weight or histopathology (NTP. 2011a; Yamada et al.. 2003; WIL Research.
2001; Ichihara et al.. 2000a; Kim et al.. 1999b; ClinTrials. 1997a. b). No human data were located.
Overall, the sparse data provide suggestive but inconclusive evidence of an association between 1-
BP exposure and immune-related outcomes. Therefore, immune effects were not considered for
dose-response analysis.
3.2.5.4 Weight of the Scientific Evidence for Reproductive and Developmental
Toxicity
Reproductive and developmental toxicity were identified as critical targets for 1-BP exposure
based on a constellation of effects reported across studies, including a two-generation reproduction
study (WIL Research. 2001). which showed adverse effects on male and female reproductive
parameters, and the developing conceptus. Additional details can be found in Appendix J.l.
Quantitative and qualitative evidence of 1-BP reproductive toxicity in F0 males include decreases
in sperm motility, changes in normal sperm morphology, decreases in mating and fertility indices
(WIL Research. 2001). and decreases in epididymal, prostate, and seminal vesicle weights
following 1-BP (whole-body) inhalation exposure (NTP. 2011a; WIL Research. 2001; Ichihara et
al.. 2000b). Evidence of reproductive toxicity in F0 females include decreased numbers of corpora
lutea, antral follicles, and implantation sites (NTP. 2011a; Yamada et al.. 2003; WIL Research.
2001). Other reported reproductive effects in females include a significant upward trend in
increased estrous cycle length, and evidence of mating without delivery (WIL Research. 2001).
Reported impairments in male and female reproductive function resulted in a 48% reduction in
fertility at 500 ppm and complete infertility at 750 ppm in F0 mating pairs (WIL Research. 2001).
Although the adverse reproductive effects of 1-BP exposure have not been directly evaluated in
humans, the results from laboratory animal studies suggest that it may impair reproductive
function.
Page 202 of 486
-------
Evidence supporting fetal development as a sensitive target of 1-BP exposure is provided by a
number of laboratory animal studies. The current database consists of developmental toxicity
testing that shows severe effects resulting from prenatal exposure during gestation and postnatal
exposure studies showing adverse developmental effects that manifest at various stages of
development, and span across multiple generations (WIL Research. 2001). Overall, the general
consistency of findings indicative of impaired development across species, as reported in multiple
studies from independent laboratories is taken as evidence of a causative association between 1-BP
exposure and developmental toxicity. Reported adverse developmental effects following 1-BP
exposure include dose-related decreases in live litter size (WIL Research. 2001). postnatal survival
(Furuhashi et al.. 2006). and pup body weight, brain weight and skeletal development (Huntingdon
Life Sciences. 1999). (Huntingdon Life Sciences. 2001); (WIL Research. 2001). (WIL Research.
2001) also reported decreases in the number of implantation sites, and increases in 'unaccounted'
implants for corresponding ovulatory events, reported as the difference between the total number
of implantation sites counted and the number of pups born. EPA interpreted this finding as an
indication of post-implantation loss (pre-implantation loss could not be determined due to
insufficient data on the number of primordial follicles). Additional qualitative evidence of impaired
development is provided by results from dominant lethal assays with 1-BP which show increased
implantation loss (at week 8) in rats subjected to five days of oral 1-BP exposure at 400 mg/kg
(Saito-Suzuki et al.. 1982) and in mice (at week 5) following 1-BP exposure via gavage
administration at 600 mg/kg for ten days prior to mating (Yu et al.. 2008). These findings are
supported by consistent reports of 1-BP induced adverse developmental effects from independent
laboratory studies with rats and mice. No corresponding epidemiological studies have been
identified; however, the concordance of reported results across species and test laboratories is
taken as evidence of a causative association between 1-BP exposure and developmental toxicity.
Overall, there is evidence in high-quality animal studies to support adverse reproductive and
developmental effects following 1-BP exposure. Therefore, these endpoints were carried forward
for dose-response analysis.
3.2.5.5 Weight of the Scientific Evidence for Neurotoxicity
Neurotoxicity has been identified as a critical effect for 1-BP based on over 15 years of behavioral,
neuropathological, neurochemical, and neurophysiological studies in rodents as well as cross-
sectional studies and case reports in humans (Appendices J.l, J.3, and J.4). Overall, there is
considerable support for the finding of peripheral neurotoxicity, and consistency in reports of
impaired peripheral nerve function (sensory and motor) and adverse neuromuscular impacts. The
effects are progressive in terms of exposure duration and concentration, and range from subtle
changes in nervous system function and neurochemistry progressing to physiological
manifestations of neuron damage to structural evidence of neuronal pathology.
This spectrum of adverse manifestations of peripheral neurotoxicity is reproducible across almost
all of the experimental studies, with a few notable exceptions. In addition, symptoms in humans,
such as peripheral weakness, numbness, ataxia, and paraparesis, are concordant with the signs seen
in many rodent studies. At high concentrations (>1000 ppm), toxicological reports in rodents
Page 203 of 486
-------
include observations such as hindlimb weakness, ataxia, altered gait, and other signs typical of
peripheral neuropathy (Mohideen et al.. 2013; Zhang et al.. 2013; Banu et al.. 2007; Honma et al..
2003; Fueta et al.. 2002a; Fueta et al.. 2002b; Ishidao et al.. 2002; Yu et al.. 2001; Fueta et al..
2000; Ichihara et al.. 2000a; Kim et al.. 1999a; Ohnishi et al.. 1999; ClinTrials. 1997a. b).
However, in a chronic bioassay (NTP. 2011a) these signs were reported at 2000 ppm but not 1000
ppm; differences in timing and specificity of observations as well as training and blinding of
personnel to dose assignment could account for the relative insensitivity of those specific
outcomes. A number of papers that did not report any information about the general appearance
and health of the animals were mostly mechanistic studies focused only on ex vivo endpoints
(Huang et al.. 2015; Huang et al.. 2012; Subramanian et al.. 2012; Huang et al.. 2011; Mohideen et
al.. 2011; Mohideen et al.. 2009; Suda et al.. 2008; Fueta et al.. 2007; Ueno et al.. 2007; Yoshida et
al.. 2007; Fueta et al.. 2004; Wang et al.. 2003; Wang et al.. 2002). In human reports, severe
neurological effects in workers occurred at relatively high exposures (>100 ppm) over a period of
time of exposure ranging from weeks to months (Samukawa et al.. 2012; CDC. 2008; Maiersik et
al.. 2007; Raymond and Ford. 2007; Ichihara et al.. 2002; Sclar. 1999).
There is general agreement between the 1-BP neurotoxic effects observed across studies using
measures of peripheral nerve integrity evaluated by electrophysiological and behavioral tests.
Nerve conduction velocity and distal latency in motor neurons are decreased in animals via
subcutaneous exposure (Yu et al.. 2001; Ichihara et al.. 2000a; Zhao et al.. 1999). These
experimental findings corroborate the studies of factory workers that describe decreased nerve
conduction and/or peripheral sensory impairment (Li et al.. 2010; Ichihara et al.. 2004a). The
epidemiological studies are, however, somewhat limited by poorly defined exposures as well as
concerns about the sensitivity and implementation of the vibration sense test methods used to
assess motor and sensory deficits. Using an objective measure of grip strength in rats, decreased
function that worsens with continued oral exposure has been reported in several laboratories
(Wang et al.. 2012; Banu et al.. 2007; Ichihara et al.. 2000a). except one (ClinTrials. 1997a).
A number of animal studies report histopathology of the nervous system (brain, spinal cord, and/or
peripheral nerves) at concentrations as low as 400 ppm (Mohideen et al.. 2013; Subramanian et al..
2012; Mohideen et al.. 2011; Wang et al.. 2002; Yu et al.. 2001; Ichihara et al.. 2000a; Ohnishi et
al.. 1999; ClinTrials. 1997b). but not in other studies that used even at higher concentrations (NTP.
2011a; Fueta et al.. 2004; Sohn et al.. 2002; WIL Research. 2001; Kim et al.. 1999a). There are a
few conflicting reports from the same laboratory in 4 week vs 13 week studies (ClinTrials. 1997a.
b), (Sohn et al.. 2002; Kim et al.. 1999a). Such differences may be attributable to a number of
experimental factors, including tissue preparation, fixation, staining, and sampling, measurement
methodology, and training and blinding of personnel to dose group assignment.
Additional experimental animal studies report changes in brain weight, which is considered
indicative of neurotoxicity even in cases where other histopathological changes are not evident
(U.S. EPA. 1998b); however, several studies do describe corresponding neuropathology (Wang et
al.. 2002; WIL Research. 2001; Kim et al.. 1999a). Decreased brain weight was reported with
subacute to subchronic exposures in adult rats (Subramanian et al.. 2012; Wang et al.. 2003;
Ichihara et al.. 2000a; Kim et al.. 1999a; ClinTrials. 1997b). and in offspring from a multi-
Page 204 of 486
-------
generational reproductive toxicity study with lifetime exposures (WIL Research. 2001). Only two
studies have measured brain weight and reported no effects: 1) (Wang et al.. 2002). in which the
duration of exposure (7 days) may not have been sufficient, and 2) the 13-wk study of (ClinTrials.
1997a). even though the same laboratory reported decreased brain weight at the same concentration
with only 4 weeks of exposure (ClinTrials did not provide explanations for this contradictory
finding).
Several studies report alterations in central nervous system neuronal communication,
neurotransmitter levels, proteins, and oxidative stress markers, all of which are markers of
neurotoxicity (U.S. EPA. 1998b). It is notable that database consistency is partially a function of
multiple studies from a few laboratories (Huang et al.. 2015; Mohideen et al.. 2013; Zhang et al..
2013; Huang et al.. 2012; Subramanian et al.. 2012; Huang et al.. 2011; Mohideen et al.. 2011;
Mohideen et al.. 2009; Suda et al.. 2008; Fueta et al.. 2007; Ueno et al.. 2007; Fueta et al.. 2004;
Wang et al.. 2003; Fueta et al.. 2002a; Fueta et al.. 2002b; Fueta et al.. 2000). Other studies have
reported cognitive deficits following 1-BP inhalation exposure (Guo et al.. 2015; Zhong et al..
2013; Honma et al.. 2003).
Overall, the experimental studies, supported by the epidemiological studies, reporting clinical and
neurophysiological signs provide strong evidence for peripheral neuropathology. Where
quantifiable endpoints that are sensitive to relatively low exposures have been measured, there is
generally good consistency in outcomes across laboratories, with only a few notable exceptions.
There is also agreement in findings of central nervous system dysfunction in laboratory rodents,
but there are no corresponding studies available for comparison in humans. There is evidence in
high-quality animal studies to support functional measures of neurotoxicity following 1-BP
exposure. Therefore, these endpoints were carried forward for dose-response analysis.
3.2.5.6 Weight of the Scientific Evidence for Cancer
Evidence from chronic cancer bioassays in rats and mice suggests that 1-BP may pose a
carcinogenic hazard to humans (IARC. 2018). Significant increases in the incidence of skin tumors
(keratoacanthoma/squamous cell carcinomas) in male F344 rats, rare large intestine adenomas in
female F344 rats, and alveolar/bronchiolar adenomas or carcinomas (combined) in female B6C3F1
mice were observed following exposure to 1-BP via whole-body inhalation for two years (NTP.
2011a). The exact mechanism/mode of action of 1-BP carcinogenesis is not established. Evidence
for a MMOA is suggestive but inconclusive. Other potential mechanisms that may contribute to the
multi-stage process of carcinogenesis by 1-BP include oxidative stress, immunosuppression, and
cell proliferation. Overall, there is evidence in high-quality animal studies to support
carcinogenicity following 1-BP exposure. Therefore, these endpoints were carried forward for
dose-response analysis.
3.2.6 Possible Mode of Action for 1-BP Toxicity
A definitive mode of action (MOA) has not been clearly established for 1-BP toxicity. Based on
the Hard and Soft Acid Base theory classification scheme (Pearson. 1990) however, 1-BP is
expected to induce adduct formation in vivo.
Page 205 of 486
-------
The primary metabolic pathways identified for 1-BP involve cytochrome P450 mediated oxidation
(CYP2E1) and glutathione conjugation reactions which can produce numerous reactive
intermediates (see Figure 3-3). Over 20 metabolites have been identified in rodent studies,
including the four metabolites detected in urine samples taken from workers exposed to 1-BP
(Hanlev et al.. 2009). These metabolites can react with critical cysteine, histidine and lysine
residues, and thereby impact the structural and functional integrity of the cell (Lopachin et al..
2009V
Various reactive metabolites (e.g., glycidol, a-bromohydrin, bromoacetone) and potential targets
for cellular binding interactions (e.g., DNA, mitochondria) have been identified for 1-BP (NTP.
2013a). Some 1-BP metabolites may exhibit alkylating activity. For example, further metabolism
of bromoacetone in a manner analogous to acetone (Casazza et al.. 1984). would result in
formation of 1-hydroxy-1-bromoacetone, which yields pyruvate and CO2, or 3-bromo-l-
hydroxypropanone (BOP). BOP has been shown to inhibit sperm energetics and motility via its
conversion to bromolactaldehyde and bromopyruvaldehyde, ultimately yielding 3-bromopyruvate
(Garner et al.. 2007; Porter and Jones. 1995).
3-Bromopyruvate (3-BP) has been shown to produce many untoward effects, including lowered
cell viability via production of reactive oxygen species (Pin et al.. 2010) mitochondrial
depolarization (Macchioni et al.. 2011) and activation of mitochondrial apoptosis (Ko et al.. 2004).
It is a strong alkylating agent, and a known inhibitor of numerous enzymes, including glutamate
decarboxylase (Fonda. 1976). glutamate dehydrogenase (Baker and Rabin. 1969). the
mitochondrial pyruvate transporter (Thomas and Halestrap. 1981) and the pyruvate dehydrogenase
complex (Apfel et al.. 1984; Lowe and Perham. 1984). 3-BP induced alkylation and inhibition of
glyceraldehyde-3-phosphate dehydrogenase can impair energy production via glycolysis (Da Silva
et al.. 2009; Ganapathy-Kanniappan et al.. 2009) and induce apoptosis or necrosis as a result of
ATP depletion due to impaired mitochondrial function (Kim et al.. 2008).
The precise mechanism of action, specific molecular targets, and precursor events (e.g., oxidative
stress response) that precede 1-BP toxicity is not clearly understood, but likely relates to structural
or functional modification of key signaling proteins as a result of cellular binding interactions
induced by 1-BP or its metabolites. Since 1-BP can induce adverse effects in multiple organs
acting directly as an alkylating agent, or indirectly via formation of reactive metabolites, different
mechanisms may be operative in different organ systems. At least four possible mechanisms (e.g.,
genotoxicity, oxidative stress, immunosuppression, and cell proliferation) have been proposed
(NTP. 2013a).
Several pathological conditions (e.g., alcoholism, diabetes), as well as chronic drug administration
can induce CYP2E1 activity, and numerous cellular targets exist for 1-BP metabolites generated
via CYP2E1 mediated oxidative metabolism. Interindividual variability in the expression and
function of CYP2E1 has been observed (Neafsev et al.. 2009) and genetic polymorphisms in
CYP2E1 expression have been linked to altered disease susceptibility (Trafalis et al.. 2010).
Though inconsistencies exist in the available data, it is suggested that chronic exposure to CYP2E1
inducers such as solvents (e.g., ethanol) and pharmaceuticals (e.g., isoniazid), may increase the
Page 206 of 486
-------
probability of developing malignancy, especially for carriers of certain CYP2E1 alleles (Trafalis et
al.. 20101
Page 207 of 486
-------
Glue
CO-
H3C
1-Bromo-2-hydroxypropane-0-glucuronide
OH
P450
Pyruvate
ch3
1-Bromopropane
HO
P450
Pyruvaldehyde
1 -bromo-2-hydroxypropane
3-Bromo-1 -hydroxypropanone
Bromoacetone
HO
HO
Br
Bromopyruvaldehyde
HO-"^
a-Bromohydrin
HO
Br
Bromolactaldehyde
Bromopyruvate
HO
OH
OH
**(GSH Conjugates not listed)
Bromolactate
Figure 3-3. Proposed Intermediary Metabolism for 1-BP
Source:(Gamer et al.. 2007: Garner et al.. 2006)
Page 208 of 486
-------
3.2.7 Summary of Hazard Studies Used to Evaluate Acute and Chronic Exposures
EPA considered adverse effects for 1-BP across organ systems and a comprehensive summary
table is in Appendix J (Table Apx J-2). The full list of effects was screened to those that are
relevant, sensitive and found in multiple studies which include the following types of effects: liver
toxicity, kidney toxicity, developmental/reproductive toxicity, neurotoxicity, and cancer as
described above. Immune effects were not considered further, as the weight of the scientific
evidence was not conclusive. In general, adverse effects were observed in all of these systems in
rats exposed to 1-BP by inhalation in the range of 100 - 1000 ppm (LOAELs). Using principles of
systematic review, EPA selected endpoints from the highest quality studies with the least
limitations for both non-cancer and cancer that were amenable to quantitative analysis for dose-
response assessment as discussed in more detail below in Section 3.2.8. In the following sections,
EPA identifies the appropriate toxicological studies to be used for acute and chronic exposure
scenarios.
3.2.8 Dose-Response Assessment
EPA evaluated data from studies described above (Section 3.2.4) to characterize the dose-response
relationships of 1-BP and selected studies and endpoints to quantify risks for specific exposure
scenarios. One of the additional considerations was that the selected key studies had adequate
information to perform dose-response analysis for the selected 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., BMD), a NOAEL or a LOAEL for an observed incidence or change in the
level of response.
3.2.8.1 Selection of Studies for Non-Cancer Dose-Response Assessment
The non-cancer dose-response analysis in this assessment commenced with the review and
selection of high quality toxicity studies that went through systematic review that reported both
adverse non-cancer health effects and quantitative dose-response data (Table 3-2). The inhalation
PODs selected (identified in earlier steps) were considered the most adverse, sensitive and
biologically relevant endpoints from among these high quality key and supporting studies. As a
result, the non-cancer dose-response assessment was organized into five health effect domains:
(1) liver; (2) kidney; (3) reproductive; (4) developmental and (5) nervous system. HEC values were
calculated for the inhalation and PODs identified within each health effect domain; dermal HED
values were extrapolated from inhalation PODs. Endpoint and study-specific UFs were selected
based on EPA guidance (U.S. EPA. 2002) and used as the benchmark MOEs for risk calculations.
These UFs were applied to the PODs to account for (1) variation in susceptibility among the human
population {i.e., inter-individual or intraspecies variability); (2) uncertainty in extrapolating animal
data to humans {i.e., interspecies uncertainty); (3) uncertainty in extrapolating from data obtained in
a study with less-than-lifetime exposure {i.e., extrapolating from subchronic to chronic exposure);
and (4) uncertainty in extrapolating from a LOAEL rather than from a NOAEL, with default values
of 10 applied for each (U.S. EPA. 2002) with two exceptions, explained further in Section 3.2.8.1.3.
Page 209 of 486
-------
Table 3-2 summarizes the hazard studies and health endpoints by target organ/system that EPA
considered suitable for carrying forward for dose-response analysis for the risk evaluation of the
exposure scenarios identified in this work plan risk assessment. These equally high quality key and
supporting studies in Table 3-2 are briefly described in the Section 3.2.4. Table 3-8 lists the most
sensitive and biologically relevant PODs (and corresponding HECs/dermal HEDs) from among
these studies by study type and duration {i.e., acute vs. chronic) that were selected to be carried
forward for risk estimations.
Benchmark dose (BMD) modeling was applied to these endpoints in a manner consistent with EPA
Benchmark Dose Technical Guidance. When the models were adequate, the model results were
used as PODs. For studies in which BMD modeling did not achieve an adequate fit to the data, the
NOAEL or LOAEL value was used for the POD. Details regarding BMD modeling can be found
in the Supplemental File: Information on Human Health Benchmark Dose Modeling (EPA. 2019d).
The PODs applied a duration adjustment to convert the air concentrations in laboratory animals for
the study duration to exposure durations for workers {i.e., 8 hours/day, 5 days/week) and exposures
of 24 hours per day for consumer exposure scenarios. Following EPA's Methods for Derivation of
Inhalation Reference Concentrations and Application of Inhalation Dosimetry (U.S. EPA. 1994).
EPA converted the adjusted POD to a human equivalent concentration (HEC) by calculating a
dosimetric adjustment factor (DAF) based on the ratio between the animal and human blood:air
partition coefficients, as shown below. For 1-BP, the blood:air partition coefficient for rats is
greater than that for humans, so a default ratio of 1 was applied (U.S. EPA. 1994). HECs/dermal
HEDs were rounded to two significant figures.
BMRs were selected for each endpoint. In cases where biologically relevant BMRs were not
available the BMR was 10% for dichotomous endpoints and 1 standard deviation for continuous
endpoints consistent with EPA Benchmark Dose Technical Guidance. The liver and kidney
endpoints were dichotomous {i.e., incidence) and a BMR of 10% was used in absence of a
biologically relevant BMR. The reproductive effects that were able to be BMD modeled (see Table
3-2) were continuous and a BMR of 1 standard deviation was used in absence of a biologically
relevant BMR. For pup body weight changes, a BMR of 5% relative deviation from control mean
was applied under the assumption that it represents a minimal biologically significant response. In
adults, a 10% decrease in body weight in animals is generally recognized as a biologically
significant response associated with identifying a maximum tolerated dose; during development,
however, identification of a smaller (5%) decrease in body weight is consistent with the
assumptions that development represents a susceptible lifestage and that the developing animal is
more adversely affected by a decrease in body weight than the adult. In humans, reduced birth
weight is associated with numerous adverse health outcomes, including increased risk of infant
mortality as well as heart disease and type II diabetes in adults (Barker. 2007; Reyes and Manalich.
2005). For these reasons, a BMR of 5% relative deviation was selected for decreased pup weight.
For post-implantation loss, a dichotomous endpoint, a BMR of 1% relative deviation was used
based on the relative severity of this endpoint considering it is similar to fetal mortality. For
decreased live litter size, a BMR of 5% relative deviation was used considering this is possibly a
combination of reproductive effects (BMR of 10% relative deviation) and developmental effects
including post-implantation loss similar to mortality (BMR of 1% relative deviation) for an overall
Page 210 of 486
-------
BMR of 5% relative deviation. A 1% BMR could potentially be justified for this endpoint as well,
however EPA believes that the 5% BMR is the most appropriate selection based on being a mix of
a reproductive and developmental effect. For decreased brain weight in F1 and F2 offspring, a
BMR of 1% relative deviation was used considering the severity of this effect and the
developmental context (e.g., could result in irreversible damage). For developmental endpoints,
BMCLs for alternative BMRs are also shown in parentheses for comparison. Alternative BMRs
were 1 standard deviation for continuous endpoints and a 10% relative deviation for dichotomous
endpoints (except for post-implantation loss the alternative BMR was a 5 % relative deviation
because of the severity of this endpoint). For functional nervous system effects, the endpoints were
continuous and a BMR of 5% ER or 1 standard deviation was used. When BMD modeling was
successful, the PODs were the BMCLs determined for each endpoint. The PODs for endpoints
selected following dose-response analysis were calculated either by benchmark dose (BMD)
modeling (when the model fit was adequate) or a NOAEL/LOAEL approach based on the endpoint
evaluated (see Section 3.2.8.1 and Table 3-2 for all of the PODs).
Given the different exposure scenarios considered (both acute and chronic for spray adhesives, dry
cleaning, and degreasing activities for occupational exposure scenarios; and only acute for spot
cleaners for consumer exposure scenarios), different endpoints were used based on the expected
exposure durations. For non-cancer effects, and based on a weight of the scientific evidence
analysis of toxicity studies from rats and humans, risks for developmental effects that may result
from a single exposure were evaluated for acute (short-term) exposures, whereas risks for other
adverse effects (e.g., toxicity to liver, kidney, reproduction, development and nervous system) were
evaluated for repeated (chronic) exposures to 1-BP. The rationale for using the range of toxic
effects for chronic scenarios is based on the fact that relatively low dose and short term/sub-
chronic exposures can result in long-term adverse consequences.
3.2.8.1.1 PODs for Acute Exposure
Acute exposure was defined for occupational settings as exposure over the course of a single work
shift 8 hours and for consumers as a single day. Developmental toxicity (i.e., post-implantation
loss; fWIL Research. 2001)) was the endpoint selected as most relevant for calculating risks
associated with acute occupational or consumer exposure. Table 3-2 summarizes the hazard studies
and health endpoints by target organ/system that EPA considered suitable for the risk evaluation of
acute exposure scenarios.
The WIL Research (2001) study scored a High in systematic review data quality criteria ranking.
The POD (post-implantation loss) was considered the most sensitive and biologically relevant
developmental toxicity endpoint and is considered to be representative of a robust dataset,
representing a continuum of adverse developmental outcomes. EPA considers the general
consistency of the effects reported across studies to be supportive of the robustness of the
developmental endpoint which exists along a continuum of adverse treatment effects, including
mortality.
Page 211 of 486
-------
The acute scenario covers exposures incurred during a single day, with varying time intervals
assumed for worker (an 8 hour work shift), and consumer (a 24 hour day) exposure scenarios.
Usually, the daily dose is not adjusted for duration of exposure because appropriate toxicokinetic
data are not available to support a more granular adjustment. In cases where such data are
available, adjustments may be made to provide an estimate of equal average concentration at the
site of action for the human exposure scenario of concern. The short half-life for 1-BP suggests
there will not be increasing body burden over multiple exposure days, therefore, effects following
single-day acute exposure can be reasonably expected to occur at the same dose as repeated
exposures and no duration adjustment is needed. Further support for using the post-implantation
loss endpoint for acute (short-term) exposures is the fact that the male and female reproductive
effects (in the Fo males and females) collectively contributed to related decreases in live litter size,
and these all occurred within a short window of exposure between ovulation and implantation. In
addition, decreased live litter size occurred at relatively low exposures, suggesting that this was a
sensitive and relevant endpoint, suitable for use in the risk assessment. A BMR of 5% was used to
address the severity of this endpoint (U.S. EPA. 2012a). This BMR choice reflects the intermediate
between reproductive effects (where a BMR of 10% would be used) and, developmental effects of
post implantation loss, (which is considered a severe effect like mortality where a BMR of 1%
would be used) inherent to the endpoint. As previously discussed, EPA acknowledges that the
severity of the endpoint, since indicating earlier prenatal mortality, could also potentially warrant a
1% BMR. The POD for the decreased live litter size was a BMCL of 31 ppm.
Additional modeling was performed using the nested dichotomous models (NCTR and NLogistic)
within BMDS version 2.7.0.4. Use of nested models is preferred for analysis of developmental
toxicity data when suitable data are available. In developmental toxicity studies, exposures are to
the dams but observations are made in the fetuses or pups, a situation in which the data are said to
be "nested." For both genetic and environmental reasons, pups in the same litter tend to be more
similar to each other than to pups in different litters (litter effect). Models for nested data
incorporate two parameters to address litter effect: a litter-specific covariate (e.g., litter size, dam
weight, etc) that takes into account the condition of the dam prior to exposure and intra-litter
correlation that statistically describes the similarity of responses to exposure among pups of the
same litter. The Nested models can only be applied to increases in effects, and therefore, increased
post-implantation loss was the endpoint selected as most relevant for calculating risks associated
with developmental toxicity following acute exposures (WIL Research. 2001) using nested
modeling.
Significant increases in the number of 'former' or 'unaccounted' implantation sites (i.e., the
difference between the total number of implantation sites counted and the number of pups born)
were reported by (WIL Research. 2001). EPA considers this finding to be indicative of post-
implantation loss (pre-implantation loss could not be determined because of a lack of data on the
number of primordial follicles at 100, 250 and 500 ppm). Fo females experienced complete
infertility at 750 ppm and therefore these exposures were not included in the post-implantation loss
modeling. Fo females experienced a 48% reduction in fertility at 500 ppm and the post-implantation
loss modeling was conducted both with and without this exposure group. After comparing the
model fits the results without the 500 ppm exposure group were selected (see the Supplemental
Page 212 of 486
-------
File: Information on Human Health Benchmark Dose Modeling (EPA. 2019d)). A BMR of 1% was
used to address the severity of this endpoint which is considered a severe effect like mortality (U.S.
EPA. 2012a). Results from the NCTR and Mogistic models demonstrated similar model fit. The
NLogistic model result was therefore selected for resulting in the lowest BMCL, however the
results were identical when rounding (22.7 ppm vs 23 ppm). The resulting POD for the increased
post-implantation loss was a BMCL of 23 ppm.
Among the two related reproductive/developmental endpoints of decreased live litter size and post-
implantation loss, the POD for post-implantation loss based on Nlogistic nested BMD modeling
will be used for risk estimation. In addition to the uncertainty over the appropriate BMR for the
decreased live litter size endpoint, the post-implantation loss endpoint allowed for nested BMD
modeling, which can capture intra-litter variability. PODs for both endpoints are shown for
comparison in Table 3-8.
3.2.8.1.2 PODs for Chronic Exposure
Chronic exposure was defined for occupational settings as exposure reflecting a 40-hour work
week. Non-cancer endpoints selected as most relevant for calculating risks associated with chronic
(repeated) occupational exposures to 1-BP included toxicity to the liver, kidney, reproductive
system, developmental effects, and the nervous system.
Table 3-2 summarizes the hazard studies and health endpoints by target organ/system that EPA
considered suitable for the risk evaluation of chronic exposure scenarios. The high quality key and
supporting studies in Table 3-2 are briefly described in the Section 3.2.4, along with other toxicity
and epidemiological studies. BMD modeling was performed for these endpoints in a manner
consistent with EPA Benchmark Dose Technical Guidance. BMRs were selected for each endpoint.
Hepatic endpoints selected for dose-response analysis include datasets for histopathology (e.g.,
hepatocellular vacuolation) from subchronic inhalation studies in rats (ClinTrials. 1997a. b) and
(WTL Research. 2001). Benchmark dose modeling determined BMCL values of 143, 226 and
322 ppm for the three datasets modeled from these studies.
Renal endpoints selected for dose-response analysis include an increased incidence of pelvic
mineralization in male and female rats from a subchronic inhalation study (WTL Research. 2001).
Benchmark dose modeling determined BMCL values for increase of pelvic mineralization of 386
ppm in male rats, and 174 ppm in female rats.
Decreased epididymal weight, decreased prostate weight, decreased seminal vesicle weight, altered
sperm morphology and decreased sperm motility were the male reproductive endpoints selected for
dose-response analysis (WTL Research. 2001; Ichihara et al.. 2000b). Increased estrous cycle
length and decreased antral follicle count were the female reproductive endpoints selected for
dose-response analysis (Yamada et al.. 2003; WIL Research. 2001). The PODs for endpoints
selected following dose-response analysis were calculated either by benchmark dose (BMD)
modeling (when the model fit was adequate) or when BMD modeling did not find an adequate
model fit a NOAEL/LOAEL approach was used and this occurred for the reproductive endpoint
evaluated (see Section 3.2.8.1 and Table 3-2 for all of the PODs). The PODs were 38, 327, 250,
Page 213 of 486
-------
313 and 338 ppm for decreased relative seminal vesicle weight (use of absolute seminal vesicle
weight produced the same BMCL), decreased percent normal sperm, decreased percent motile
sperm, and absolute left and right cauda epididymal weights respectively, in males. The PODs
were 200 and 250 ppm for decreased antral follicle count and increased estrous cycle length
respectively, in females.
Decreased live litter size {i.e., reduced number of live pups per litter) was the endpoint selected as
most relevant for calculating risks associated with developmental toxicity following chronic,
exposures (WIL Research. 2001). In addition, decreased live litter size occurred at relatively low
exposures, suggesting that this was a sensitive and relevant endpoint, suitable for use in the risk
assessment. A BMR of 5% was used to address the severity of this endpoint (U.S. EPA. 2012a). The
POD for the decreased live litter size was a BMCL of 43 ppm. EPA acknowledges that the severity
of the endpoint, since indicating prenatal mortality, could also potentially warrant a 1% BMR.
As discussed above for acute exposure, EPA used the BMDS nested dichotomous model
(NLogistic) to model data for increased post-implantation loss while accounting for litter effects.
Again, a BMR of 1% was used to address the severity of this endpoint (U.S. EPA. 2012a). The
POD for the increased post-implantation loss was a BMCL of 23 ppm.
Neurological endpoints selected for dose-response analysis for chronic, repeated exposures were
datasets for decreased time hanging from a suspended bar (traction time) in rats in a 3-week
inhalation study (Honma et al.. 2003). decreased hind limb grip strength in rats in a 12-week
inhalation study (Ichihara et al.. 2000a) and decreased brain weight in adult (F0) rats (WIL
Research. 2001). The functional measures (decreased time hanging and decreased hind limb
strength) are relevant to peripheral neurotoxicity reported in human studies. Benchmark dose
modeling for these continuous endpoints used a BMR of 1 standard deviation and determined
BMCL values of 18 and 147 ppm, respectively, for these datasets. A BMR of 5% was used to
address the severity of the decreased brain weight in adult (F0) rats endpoint (U.S. EPA. 2012a).
3.2.8.1.3 Uncertainty Factor Determinations
The benchmark MOE used to evaluate risks for each use scenario represents the product of all UFs
used for each non-cancer POD. These UFs accounted for various uncertainties including:
1. Animal-to-human extrapolation (UFa): The UFa accounts for the uncertainties in
extrapolating from rodents to humans. In the absence of data, the default UFA of 10 is
adopted which breaks down to a factor of 3 for toxicokinetic variability and a factor of 3 for
toxicodynamic variability. There is no PBPK model for 1-BP to account for the interspecies
extrapolation using rodent toxicokinetic data in order to estimate internal doses for a
particular dose metric. In this assessment, a portion of the toxicokinetic uncertainty may be
accounted for by the calculation of an HEC accounting for the relative blood/air partition
coefficients across species and application of a dosimetric adjustment factor as outlined in the
RfC methodology (U.S. EPA. 1994); however, an UFa of 10 is retained to account for
additional toxicokinetic differences that remain unaccounted for. 1-BP is irritating to the
respiratory tract and rodents exhibit physiological responses (such as reflex bradypnea) that
Page 214 of 486
-------
differ from humans and may alter uptake due to hyper- or hypoventilation, resulting in
decreased internal dose in rodents relative to the applied concentration. Therefore, an UFa of
10 is retained to account for toxicokinetic differences (OECD 39).
2. Inter-individual variation (UFh): The UFH accounts for the variation in sensitivity within
the human population. In the absence of data, the default UFH of 10 is adopted which breaks
down to a factor of 3 for toxicokinetic variability and a factor of 3 for toxicodynamic
variability. Since there is no PBPK model for 1-BP to reduce the human
toxicokinetic/toxicodynamic variability, the total UFH of 10 was retained.
3. Extrapolation from subchronic to chronic (UFs): The UFS accounts for the uncertainty in
extrapolating from a subchronic to a chronic POD. Typically, a UFS of 10 is used to
extrapolate a POD from a less-than-chronic study to a chronic exposure, except for
reproductive/developmental endpoints where a study may cover the full duration of relevant
developmental or reproductive processes. However, with few exceptions, the vast majority of
the five health effect domains (liver, kidney, reproductive, developmental and nervous
system), were observed in the multi-generational reproductive toxicity study with lifetime
exposures (WTL Research. 2001); other studies, ClinTrials. 1997a. b (for liver effects), and
Ichihara et al.. 2000b and Yamada et al.. 2003 (for reproductive effects) were longer-term
studies. The only exception was for nervous system effects observed in the 3-week study by
Honma et al.. 2003. However, the totality of information in animal studies support nervous
system effects at similar concentrations following chronic exposures to 1-BP. In addition,
longer term (2 weeks up to 9 years) exposures in humans (case-control studies, industrial
surveys, and case reports) also corroborate the nervous system as a sensitive target of 1-BP
exposure (Samukawa et al.. 2012; Maiersik et al.. 2007; Raymond and Ford. 2007; Ichihara et
al.. 2002; Sclar. 1999); (NIOSH. 2003a. 2002a. c). Since exposures in the longer-term animal
studies are not reasonably expected to cause equivalent nervous system effects at a lower
concentration than the 3-week study by Honma et al.. 2003. a UFS of 1 was used for all of the
HECs discussed in EPA's risk evaluation.
4. LOAEL-to-NOAEL extrapolation (UFL): The UFL accounts for the uncertainty in
extrapolating from a LOAEL to a NOAEL. A value of 10 is the standard default UFL value
(when a LOAEL was used as the POD), although lower values (e.g., 3) can be used if the
effect is considered minimally adverse at the LOAEL or is an early marker for an adverse
effect (U.S. EPA. 2002). Typically, UFL ranging from 3 to 30 (i.e., 3, 10, or 30) are used in the
HECs. A LOAEL was used as the POD in only two instances; one reproductive POD (Yamada
et al.. 2003) and one developmental POD (WTL Research. 2001). For these PODs, the default
UFl value of 10 was used, resulting in a total UF of 1000. For all other PODs, a UFl of 1 was
used and the total UF was 100.
All endpoints evaluated for dose-response modeling and their associated UFs are provided in Table
3-2.
Page 215 of 486
-------
Table 3-2. Endpoints Selected for the Inhalation Non-Cancer Dose-Response Analysis of 1-BP
Target Organ/
System
Species, sex
(#animals/
dose)
Range of
Cone.1
(ppm)
Duration2
POD
Type
(ppm)3
Effect
HEC
(ppm)4
Uncertainty
Factors (UFs) for
Benchmark
MOE5
Reference
Data
Quality
Ranking7
Liver
Rat (male)
(n=25/group)
100 to
750
6 hours/day during
pre-mating (> 70
days), throughout
mating, and until
sacrifice for F0
BMCLi,:,=
143
Increased
incidence of
vacuolization
of
centrilobular
hepatocytes
(Fo)
150
UFs=1;UFa=10;
UFh=10;UFl=1;
Total UF=100
(WIL
Research.
2001)
High
(1.2)
Liver
Rat (male)
(n=15/group)
100 to
600
6 hours/day, 5
days/week for 13
weeks
BMCLi,:,=
226
Increased
incidence of
cytoplasmic
vacuolization
170
UFs=1;UFa=10;
UFh=10;UFl=1;
Total UF=100
(ClinTrials.
1997a)
High
(1.5)
Liver
Rat (female)
(n=25/group)
100 to
750
6 hours/day during
pre-mating (> 70
days), throughout
mating, and until GD
20; from PND 5 until
weaning of offspring
(~PND 21) for F0
BMCLi,:,=
322
Increased
incidence of
vacuolization
of
centrilobular
hepatocytes
(Fo)
340
UFs=1;UFa=10;
UFh=10;UFl=1;
Total UF=100
(WIL
Research.
2001)
High
(1.2)
Kidney
Rat (female)
(n=25/group)
100 to
750
6 hours/day during
pre-mating (> 70
days), throughout
mating, and until GD
20; from PND 5 until
weaning of offspring
(~PND 21) for F0
BMCLi,:,=
174
Increased
incidence of
pelvic
minerali-
zation (Fo)
180
UFs=1;UFa=10;
UFh=10;UFl=1;
Total UF=100
(WIL
Research.
2001)
High
(1.2)
Kidney
Rat (male)
(n=25/group)
100 to
750
6 hours/day during
pre-mating (> 70
days), throughout
mating, and until
sacrifice for F0
BMCLi,:,=
386
Increased
incidence of
pelvic
minerali-
zation (Fo)
405
UFs=1;UFa=10;
UFh=10;UFl=1;
Total UF=100
(WIL
Research.
2001)
High
(1.2)
Page 216 of 486
-------
Target Organ/
System
Species, sex
(#animals/
dose)
Range of
Cone.1
(ppm)
Duration2
POD
Type
(ppm)3
Effect
HEC
(ppm)4
Uncertainty
Factors (UFs) for
Benchmark
MOE5
Reference
Data
Quality
Ranking7
Reproductive
System
Rat (male)
(n=8-9/group)
200 to
800
8 hours/day, 7
days/week for 12
weeks
BMCLisd
= 38
Decreased
absolute/
relative
seminal
vesicle
weight
53
UFs=l; UFa=10;
UFh=10; UFl=1;
Total UF=100
(Icliihara et
al.. 2000b)
High
(1.7)
Reproductive
System
Rat (female)
(n=22-
25/group)
100 to
500
6 hours/day during
pre-mating (> 70
days), throughout
mating, and until
sacrifice for F0
BMCLisd
= 188
Decreased
number of
implantation
sites
200
UFs=l; UFa=10;
UFh=10; UFl=1;
Total UF=100
(WIL
Research.
2001)
High
(1.2)
Reproductive
System
Rat (male)
(n=15-
25/group)
100 to
750
6 hours/day during
pre-mating (> 70
days), throughout
mating, and until
sacrifice for F0
NOAF.T/=
250
Decreased
percent
motile sperm
(Fo)
260
UFs=l; UFa=10;
UFh=10; UFl=1;
Total UF=100
(WIL
Research.
2001)
High
(1.2)
Reproductive
System
Rat (female)
(n=22-
25/group)
100 to
750
6 hours/day during
pre-mating (> 70
days), throughout
mating, and until GD
20; from PND 5 until
weaning of offspring
(~PND 21) for F0
NOAEL*=
250
Increase in
estrous cycle
length (Fo)
260
UFs=l; UFa=10;
UFh=10; UFl=1;
Total UF=100
(WIL
Research.
2001)
High
(1.2)
Reproductive
System
Rat (female)
(n=10/
group)
200 to
800
8 hours/day, 7
days/week for 7 or 12
weeks
LOAEL*=
200
Decreased
number of
antral
follicles (Fo)
280
UFs=l; UFa=10;
UFh=10; UFl=10;
Total UF=1000
(Yamada et
al.. 2003)
High
(1.6)
Page 217 of 486
-------
Target Organ/
System
Species, sex
(#animals/
dose)
Range of
Cone.1
(ppm)
Duration2
POD
Type
(ppm)3
Effect
HEC
(ppm)4
Uncertainty
Factors (UFs) for
Benchmark
MOE5
Reference
Data
Quality
Ranking7
Reproductive
System
Rat (male)
(n=25/group)
100 to
750
6 hours/day during
pre-mating (> 70
days), throughout
mating, and until
sacrifice for F0
BMCLisd
= 313
Decreased
left cauda
epididymis
absolute
weight (Fo)
330
UFS=1; UFa=10;
UFh=10; UFl=1;
Total UF=100
(WIL
Research.
2001)
High
(1.2)
Reproductive
System
Rat (male)
(n=24-
25/group)
100 to
750
6 hours/day during
pre-mating (> 70
days), throughout
mating, and until
sacrifice for F0
BMCLisd
= 223
Decreased
percent
normal sperm
morphology
(Fo)
234
UFS=1; UFa=10;
UFh=10; UFl=1;
Total UF=100
(WIL
Research.
2001)
High
(1.2)
Reproductive
System
Rat (male)
(n=25/group)
100 to
750
6 hours/day during
pre-mating (> 70
days), throughout
mating, and until
sacrifice for F0
BMCLisd
= 338
Decreased
right cauda
epididymis
absolute
weight (Fo)
350
UFS=1; UFa=10;
UFh=10; UFl=1;
Total UF=100
(WIL
Research.
2001)
High
(1.2)
Reproductive
System
Rat
(n=25/group)
100 to
750
6 hours/day during
pre-mating (> 70
days), throughout
mating, and until
sacrifice for F0
BMCLi,:,=
356
Decreased
Male and
Female
Fertility
Index (Fo)
370
UFS=1; UFa=10;
UFh=10; UFl=1;
Total UF=100
(WIL
Research.
2001)
High
(1.2)
Developmental
Effects
(BMDS nested
dichotomous
model,
NLogistic)
Rat
(n=25/
group)
100 to
500
6 hours/day during
pre-mating (> 70
days), throughout
mating, and until GD
20 for the Fi litters
BMCLi=
23
(BMCL5
=89)
Post-
implantation
loss in Fo
females
Acute6:
17
Chronic6:
17
UFS=1; UFa=10;
UFh=10; UFl=1;
Total UF=100
(WIL
Research.
2001)
High
(1.2)
Developmental
Effects
(BMD
modeling)
Rat
(n=25/group)
100 to
500
6 hours/day during
pre-mating (> 70
days), throughout
mating, and until GD
20 for the Fi litters
bmcl5=
41
(BMCLisd
=158)
Decreased
live litter size
(Fi)atPNDO
Acute6:
31
Chronic6:
31
UFS=1; UFa=10;
UFh=10; UFl=1;
Total UF=100
(WIL
Research.
2001)
High
(1.2)
Page 218 of 486
-------
Target Organ/
System
Species, sex
(#animals/
dose)
Range of
Cone.1
(ppm)
Duration2
POD
Type
(ppm)3
Effect
HEC
(ppm)4
Uncertainty
Factors (UFs) for
Benchmark
MOE5
Reference
Data
Quality
Ranking7
Developmental
Effects
Rat
(female)
(n=15-
22/group)
100 to
500
6 hours/day during
pre-mating (> 70
days), throughout
mating, and until GD
20; from PND 5 until
weaning of offspring
(-PND21)
BMCLi=
50
(BMCLisd
=260)
Decreased
brain weight
in F2 females
at PND 21
53
UFs=1;UFa=10;
UFh=10;UFl=1;
Total UF=100
(WIL
Research.
2001)
High
(1.2)
Developmental
Effects
Rat
(female)
(n=25/group)
100 to
500
6 hours/day during
gestation plus >21
weeks after PND21
BMCLi=
82
(BMCLisd
=327)
Decreased
brain weight
in adult Fi
females
86
UFs=1;UFa=10;
UFh=10;UFl=1;
Total UF=100
(WIL
Research.
2001)
High
(1.2)
Developmental
Effects
Rat
(male)
(n=15-
22/group)
100 to
500
6 hours/day during
pre-mating (> 70
days), throughout
mating, and until GD
20; from PND 5 until
weaning of offspring
(-PND21)
BMCLi=
98
(BMCLisd
=395)
Decreased
brain weight
in F2 males at
PND 21
100
UFs=1;UFa=10;
UFh=10;UFl=1;
Total UF=100
(WIL
Research.
2001)
High
(1.2)
Developmental
Effects
Rat
(male)
(n=24-
25/group)
100 to
500
6 hours/day during
gestation plus >21
weeks after PND21
LOAEL* =
100
Decreased
brain weight
in adult Fi
males
110
UFs=1;UFa=10;
UFh=10; UFl=10;
Total UF=1000
(WIL
Research.
2001)
High
(1.3)
Developmental
Effects
Rat
(male)
(n=15-
22/group)
100 to
500
6 hours/day during
gestation until GD 20
and from PND 5 until
weaning (~PND 21)
for F2
bmcl5=
116
(BMCLisd
=249)
Decreased
pup body
weights
on PND 21
(F2 males)
120
UFs=1;UFa=10;
UFh=10;UFl=1;
Total UF=100
(WIL
Research.
2001)
High
(1.3)
Page 219 of 486
-------
Target Organ/
System
Species, sex
(#animals/
dose)
Range of
Cone.1
(ppm)
Duration2
POD
Type
(ppm)3
Effect
HEC
(ppm)4
Uncertainty
Factors (UFs) for
Benchmark
MOE5
Reference
Data
Quality
Ranking7
Developmental
Effects
Rat
(male)
(n=10-
24/group)
100 to
500
6 hours/day during
gestation until GD 20
and from PND 5 until
weaning (~PND 21)
for Fi
bmcl5=
123
(BMCLisd
=229)
Decreased
pup body
weights
on PND 28
(Fi males)
130
UFS=1; UFa=10;
UFh=10; UFl=1;
Total UF=100
(WIL
Research.
2001)
High
(1.3)
Developmental
Effects
Rat
(female)
(n=15-
22/group)
100 to
500
6 hours/day during
gestation until GD 20
and from PND 5 until
weaning (~PND 21)
for F2
NO art:
= 250
Decreased
pup body
weights
on PND 14
(F2 females)
260
UFS=1; UFa=10;
UFh=10; UFl=1;
Total UF=100
(WIL
Research.
2001)
High
(1.3)
Developmental
Effects
Rat
(male)
(n=15-
22/group)
100 to
500
6 hours/day during
gestation until GD 20
and from PND 5 until
weaning (~PND 21)
for F2
bmcl5=
136
(BMCLisd
=290)
Decreased
pup body
weights
on PND 14
(F2 males)
300
UFS=1; UFa=10;
UFh=10; UFl=1;
Total UF=100
(WIL
Research.
2001)
High
(1.3)
Developmental
Effects
Rat
(female)
(n=15-
22/group)
100 to
500
6 hours/day during
gestation until GD 20
and from PND 5 until
weaning (~PND 21)
for F2
bmcl5=
148
(BMCLisd
=300)
Decreased
pup body
weights
on PND 21
(F2 females)
320
UFS=1; UFa=10;
UFh=10; UFl=1;
Total UF=100
(WIL
Research.
2001)
High
(1.3)
Nervous System
Rat
(male)
(n=5/group)
10 to
1000
8 hours/day, 7
days/week for 3 weeks
BMCLisd
= 18
Decreased
time hanging
from a
suspended
bar (traction
time)
25
UFS=1; UFa=10;
UFh=10; UFl=1;
Total UF=100
(Homna et
al.. 2003)
High
(1.6)
Nervous System
Rat
(male)
(n=25/group)
100 to
750
6 hours/day during
pre-mating,
throughout mating,
and until GD 20 (> 16
weeks)
NOAEL*
= 100
Decreased
brain weight
in Fo males
110
UFS=1; UFa=10;
UFh=10; UFl=1;
Total UF=100
(WIL
Research.
2001)
High
(1.3)
Page 220 of 486
-------
Target Organ/
System
Species, sex
(#animals/
dose)
Range of
Cone.1
(ppm)
Duration2
POD
Type
(ppm)3
Effect
HEC
(ppm)4
Uncertainty
Factors (UFs) for
Benchmark
MOE5
Reference
Data
Quality
Ranking7
Nervous System
Rat
(male)
(n=8-9/group)
200 to
800
8 hours/day, 7
days/week for 12
weeks
BMCLisd
= 147
Decreased
hind limb
grip strength
206
UFs=1;UFa=10;
UFh=10; UFl=1;
Total UF=100
(Ichihara et
al.. 2000a)
High
(1.3)
Nervous System
Rat
(female)
(n=25/group)
100 to
750
6 hours/day during
pre-mating,
throughout mating,
and until GD 20 (> 16
weeks)
BMCLs =
584
(BMCLisd
= 509)
Decreased
brain weight
in Fo females
610
UFs=1;UFa=10;
UFh=10;UFl=1;
Total UF=100
(WIL
Research.
2001)
High
(1.3)
Control concentrations are not included in the table.
2 Acute exposures defined as those occurring within a single day. Chronic exposures defined as 10% or more of a lifetime (U.S. EPA. 2011).
3POD type can be NOAEL, LOAEL, or BMCL. For BMCLs, the subscript indicates the associated BMR. The BMRs are a percentage relative deviation (e.g., 10%
relative deviation BMCLio) or 1 standard deviation change (BMCLisd) from the mean for continuous data. Post-implantation loss was modeled with nested modeling to
account for intra-litter correlations and litter-specific covariates. The dam weight litter specific covariate and without intra-litter correlations for the NLogistic model
was the selected model based on lowest AICs and lowest BMCL.
4HECs are calculated by duration adjustment and a human equivalent DAF. The adjusted POD is the POD x duration adjustment. The HECexresp = adjusted POD x
DAF where the DAF is the ratio of blood:gas partition coefficients (animal:human). For 1 -BP, the blood:air partition coefficient for rats is greater than that for humans,
so a default ratio of 1 is applied (U.S. EPA. 1994). The baseline used for the duration adjustment was an 8 hours/day exposure for occupational exposure scenarios and
24 hours/day exposure for consumer exposure scenarios. For acute exposure the duration adjustment was (hours per day exposed ^ 8) and for chronic exposure
(occupational scenarios) was (hours per day exposed 8) x (days per week exposed 5) to reflect a 40-hour work week. All of the endpoints used the chronic exposure
duration adjustment except for the decreased live litter size (Fi) at PND 0 and post implantation loss as described above in Section 3.2.8.1. HECs are rounded to two
significant digits.
5UFS = subchronic to chronic UF (default value = 10); UFA = interspecies UF (default value of 10); UFH = intraspecies UF (default value = 10); UFL = LOAEL to
NOAEL UF (default value = 10) (U.S. EPA. 2002). Rationale for selection of specific UF values used to calculate the benchmark MOE for the key studies used in risk
is presented in Section 4.2.1. Narratives explaining overall UF determinations are provided in Section 3.2.8.1.
6The HEC for decreased live litter size and post-implantation loss were adjusted for acute and chronic occupational exposures as described in footnote 4.
* BMD modeling did not adequately fit the variance in the data so the NOAEL or LOAEL is presented.
7 Data Quality Criteria Ranking: High > = 1 and < 1.7; Medium >= 1.7 and < 2.3; Low >=2.3 and <=3; The numbers in parentheses reflect the score associated with the
ranking. Lower scores reflect higher quality studies. Higher scores, reflect lower quality studies.
Page 221 of 486
-------
3.2.8.2 Selection of Studies for Carcinogenic Dose-Response Assessment
No data were located on the carcinogenicity of 1-BP in humans. In animals, the carcinogenicity of
1-BP was evaluated in well-designed studies conducted in rodents (NTP. 2011a). Male and female
rats and mice were exposed to 1-BP via whole-body inhalation 6 hours/day, 5 days/week for 2
years. Cancer findings included significant increases in the incidences of: 1) skin tumors
(keratoacanthoma/squamous cell carcinomas) in male F344 rats, 2) rare large intestine adenomas in
female F344 rats, and 3) alveolar/bronchiolar adenomas and carcinomas (combined) in female
B6C3F1 mice.
3.2.8.2.1 Cancer Dose-Response Modeling
Benchmark dose-response modeling of the (NTP. 2011a) cancer data was performed for all three
statistically significantly increased tumor types from the NTP study {i.e., skin tumors in male rats,
intestinal tumors in female rats, and lung tumors in female mice). A brief summary of the
methodology is presented here and more details are available in the Supplemental File:
Information on Human Health Benchmark Dose Modeling (EPA. 2019d). Three approaches were
applied; multistage modeling, frequentist model-averaging and Bayesian model averaging. The
three approaches include the approach under EPA's 2005 cancer guidelines {i.e., multistage
modeling) and two model averaging methods. The model averaging methods allow for an
assessment of model uncertainty as described further below. Two options for BMR (0.1% and
10%) added or extra risk were both modeled for comparison with EPA's 2005 cancer guidelines
and comparison with the 2 aft Risk Assessment (U.S. EPA. 2016c) and the 2016 NIOSH
draft criteria document.
In agreement with EPA's long-standing approach, all three tumor types from the NTP study (NTP.
201 la) were modeled with the cancer model in EPA's BMDS (U.S. EPA. 2012a). EPA prefers to
use the multistage model with constrained model coefficients >0 for dose-response modeling of
cancer bioassay data. The multistage model is a family of different stage polynomial models. The
multistage model is preferred because it is sufficiently flexible for most cancer bioassay data, and
its use provides consistency across cancer dose-response analyses. There is precedent and some
biological support for use of multistage models for cancer. Under U.S. EPA's 2005 cancer
guidelines (U.S. EPA. 2005a). quantitative risk estimates from cancer bioassay data were
calculated by modeling the data in the observed range to estimate a BMCL for a BMR of 10%
extra risk, which is generally near the low end of the observable range for standard cancer bioassay
data. The BMCs and BMCLs are shown in Table 3-3 in the Multistage columns for each of the
three cancer datasets. Also, the results for a BMR of 0.1% added risk are presented for comparison.
In addition to the multistage modeling, model averaging methods were applied, frequentist
(Wheeler and Bailer. 2007) and Bayesian (USEPA 2018 BMDS software) to assess the impact of
model uncertainty. In the 2 aft Risk Assessment (U.S. EPA. 2016c). all dichotomous models
in the BMD software (gamma, logistic, log-logistic, multistage, probit, log-probit, quantal-linear,
and Weibull in BMDS Version 2.6) were fit to the incidence data for each of the three tumor types.
The benchmark response level (BMR) used was 0.1% added risk (corresponding to a l-in-1,000
working lifetime added risk of cancer) consistent with the 2016 NIOSH draft criteria document. A
Page 222 of 486
-------
model-averaging (MA) technique (Wheeler and Bailer. 2007) was applied using 3 models that
performed better in bias and coverage than other combinations of models (the multistage, log-
probit and Weibull models) and applied statistics (bootstrapping technique) to weigh, based on fit,
the models providing acceptable fit to the experimental dataset (Wheeler and Bailer. 2007). Model-
averaging software was restricted to avoid supralinear models, which exhibit properties at the low
dose that are not considered biologically plausible. The resulting model-average benchmark
concentrations (MA BMCs) associated with 0.1% added risk and their 95% lower confidence
limits (MA BMCLs) are shown in Table 3-3 in the Frequentist Model-Average (BMDS 2.6)
column for each of the three cancer datasets.
Since the 2016 Draft Risk Assessment (U.S. EPA. 2016c). EPA has conducted an additional third
type of modeling, using the BMDS (Version 3.0) and more details are available in the
Supplemental File: Information on Human Health Benchmark Dose Modeling (EPA. 2019d). In
this third modeling approach all dichotomous frequentist and Bayesian33 models in the BMD
software (BMDS Version 3.0), were fit to the incidence data for each of the three tumor types and
the Bayesian model averaging approach was applied (see the for more description BMDS 3 .0 User
Guide). To compare with the modeling in the 2016 Draft Risk Assessment (U.S. EPA. 2016c)
which used 0.1% added risk (AR), in this modeling used BMR levels of 0.1% and 10% added and
extra risk (ER). The BMR of 10% ER which is generally near the low end of the observable range
for standard cancer bioassay data is the approach under EPA's 2005 cancer guidelines. The
resulting model-average benchmark concentrations (MA BMCs) associated with 0.1% added risk
(AR) and 10% extra risk (ER) and their 95% lower confidence limits (BMCLs), are shown in
Table 3-3 in the Bayesian Model-Average (BMDS 3.0) column for each of the three cancer
datasets.
Table 3-3. Multistage Model, Model-Average (BMDS Version 2.6), and Model-Average
(BMDS Version 3.0) BMC and BMCL Estimates of 1-BP Inhalation Exposure Associated
with a 0.1% Added Risk and 10% Extra Risk of Tumors in Rodents
Multistage Model
Frequentist Model-
Average
(BMDS 2.6)
Bayesian Model-
Average
(BMDS 3.0)
Species; Tumor Type
BMR
BMC
(ppm)1
BMCL
(ppm)1
BMC
(ppm)
BMCL
(ppm)
BMC
(ppm)
BMCL
(ppm)
Male F344 rats;
keratoacanthoma/squamous cell
carcinoma (combined)
0.1% AR
2.96
1.78
3.73
2.25
9.81
1.47
10% ER
303.8
185.2
--
--
433.5
220.6
Female F344 rats; large intestine
adenoma
0.1% AR
5.27
3.10
13.5
4.85
23.8
7.98
10% ER
555.3
326.7
--
--
601.5
392.4
0.1% AR
0.77
0.52
0.85
0.64
1.51
0.085
33 The Bayesian dichotomous models used in BMDS 3.0 are identical to the frequentist parametric models but
incorporate prior information (e.g., parameter distributions) that is used in the model fit (cite BMDS 3.0 User Guide
for details; https://www.epa.gov/bmds/benclimark-dose-software-bmds-version-30-user-guide-readme).
Page 223 of 486
-------
Female B6C3F1 mice;
alveolar/bronchiolar adenoma or
10% ER
78.6
54.1
--
--
104.6
39.4
carcinoma (combined)
1 First degree Multistage model was selected for all tumor datasets.
Extrapolation to Humans
The human equivalent values shown in Table 3-4 and Table 3-5 are extrapolated from the BMC
and BMCL results to generate the target response in rodents exposed 6 hours/day for 5 days/week.
The BMC and BMCL values are extrapolated to BMChec and BMCLhec and shown in Table 3-4
based on occupational inhalation exposure to 1-BP during a 40-hour work week (8 hours/day, 5
days/week) or continuous 24 hours/day and 7 days/week. The dermal BMDhed and BMDLhed
from the BMC and BMCL values are shown in Table 3-5.
These data were extrapolated to humans based on occupational exposure to 1-BP during a 40-hour
work week (8 hours/day, 5 days/week) using the following methodology:
1. Conversion of BMC/BMCLs (ppm) to benchmark dose values (BMD/BMDL in mg/kg-
day) by adjusting for the animal breathing rate and experimental exposure duration 6
hours/day34;
2. Conversion of BMD/BMDLs in rodents to human equivalent BMD/BMDLs on the basis of
the mg/kg-day dose scaled by body weight to the 0.75 power35 and assuming dermal
absorption is equivalent to inhalation absorption the BMD is the dermal HED; and
3. Adjustment of the human equivalent BMD/BMDLs (mg/kg-day) to BMC/BMCLs (ppm)
that reflect exposure for either an 8-hour work day or 24-hour continuous exposure36.
The human equivalent BMC and BMCL (BMChec and BMCLhec) estimates using all three
modeling approaches are shown in Table 3-4. Three combinations of modeling inputs are shown -
the multistage BMR 10% extra risk (ER) i.e., the approach under EPA's 2005 cancer guidelines,
frequentist model averaging BMR 0.1% added risk for comparison with the 2 aft Risk
Assessment (U.S. EPA. 2016c) and the 2016 NIOSH draft criteria document and Bayesian Model
34BMD/BMDL (mg/kg-day) = BMC/BMCL (ppm) x (6 hours/24 hours) x (5.031 mg/m3 per ppm) x default inhalation
rate (m3/day) default body weight (kg); where the default inhalation rate and body weight values are 0.36 m3/day and
0.380 kg for male F344 rats, 0.24 m3/day and 0.229 kg for female F344 rats, and 0.06 m3/day and 0.0353 kg for female
B6C3F1 mice in chronic studies (U.S. EPA. 1988).
35Human equivalent BMD/BMDL (mg/kg-day) = BMC/BMCL (mg/kg-day) x default body weight in rats or mice [kg]
x (default body weight in humans [kg] default body weight in rats or mice [kg]) 0 75 default body weight in humans
[kg]; where default body weight values are 0.380 kg for male F344 rats, 0.229 kg for female F344 rats, 0.0353 kg for
female B6C3F1 mice, and 70 kg for humans (U.S. EPA. 1988: ICRP. 1975).
36BMC/BMCL (ppm) = (1 ppm per 5.031 mg/m3) x (default body weight in humans [kg]/default minute volume for
human occupational exposure based on an 8-hour shift [m3/day] or a continuous exposure for 24-hours); where default
body weight and minute volume values are 70 kg and 9.6 m3/8-hr day or 15 m3/24-hr day (U.S. EPA. 1994).
Page 224 of 486
-------
averaging BMR 10% ER as the latest modeling approach in BMDS. Since these BMCLs are for
different BMRs they are not directly comparable.
Table 3-4. BMChec and BMCLhec Estimates of 1-BP Inhalation Exposures in Humans
Exposed 40 hours/week (8 hours/day, 5 days/week) (ppm) or 24 hrs/day 7 days/week (ppm)
Multistage Model
BMR 10% ER
Frequentist Model-
Average
(BMDS 2.6)
BMR 0.1% AR
Bayesian Model-
Average
(BMDS 3.0)
BMR 10% ER
Species; Tumor Type
Exposure
duration
BMChec
(ppm)
BMCLhec
(ppm)
BMChec
(ppm)
BMCLhec
(ppm)
BMChec
(ppm)
BMCLhec
(ppm)
Male F344 rats;
keratoacanthoma/squamous
cell carcinoma (combined)
40 lirs/wk
141
86
1.73
1.04
200
102
24 hrs/day
90
55
1.01
0.67
128
65
Female F344 rats; large
intestine adenoma
40 lirs/wk
254
149
6.17
2.22
275
179
24 hrs/day
162
96
3.95
1.42
176
115
Female B6C3F1 mice;
alveolar/bronchiolar adenoma
or carcinoma (combined)
40 lirs/wk
36
25
0.39
0.30
49
18
24 hrs/day
23
16
0.25
0.19
31
12
Table 3-5. BMDhed and BMDLhed Estimates of 1-BP Dermal Exposures Extrapolated from
BMC and BMCL (mg/kg-day)
Multistage Model
BMR 10% ER
Frequentist Model-
Average
(BMDS 2.6)
BMR 0.1% AR
Bayesian Model-
Average
(BMDS 3.0)
BMR 10% ER
Species; Tumor Type
BMDhed
(mg/kg/d)
BMDLhec
(mg/kg/d)
BMDhed
(mg/kg/d)
BMDLhec
(mg/kg/d)
BMDhed
(mg/kg/d)
BMDLhec
(mg/kg/d)
Male F344 rats;
keratoacanthoma/squamous cell
carcinoma (combined)
97
59
1.19
0.72
138
70
Female F344 rats; large intestine
adenoma
175
103
4.26
1.53
190
124
Female B6C3F1 mice;
alveolar/bronchiolar adenoma or
carcinoma (combined)
25
17
0.27
0.21
34
13
Derivation of Inhalation Unit Risk Applying Age-Dependent Adjustment Factors (ADAFs)
Using the mode of action framework, age-dependent adjustment factors (ADAFs) are applied when
developing cancer risk estimates when early-life susceptibility is assumed (ages 0-15) and when
there is evidence of a MMOA in animal studies (EPA's Guidelines for Carcinogen Risk
Assessment (U.S. EPA 2005a); Supplemental Guidance for Assessing Susceptibility from Early
Life Exposure to Carcinogens (U.S. EPA 2005b). For 1-BP, the weight of the scientific evidence
is suggestive but inconclusive that 1-BP is carcinogenic by a MMOA (see Appendix K); and early-
Page 225 of 486
-------
life chronic exposure scenarios are assumed only for the inhalation route, and only for occupational
scenarios for worker populations. ADAFs were not applied for any occupational scenarios in this
risk evaluation because there is insufficient evidence to definitively conclude that 1-BP is
carcinogenic by a MMOA and because worker populations are considered to be 16 years of age
and older, ages not covered by the ADAF application guidance (U.S. EPA. 2005b). ADAFs also
were not applied for younger-aged children spending time in the workplace (e.g., family owned
businesses) because a MMOA has not been established and because it is unlikely their exposures
are chronic in nature.
Derivation of Inhalation Unit Risk and Dermal Slope Factor
The data for lung tumors based on the combined incidence of alveolar/bronchiolar adenoma or
carcinoma in female mice (as shown in Section 3.2.8.2) was selected for derivation of the
inhalation unit risk (IUR) and for the dermal slope factor. This POD is considered protective for
the other tumor types. The BMCLhec values for both a 40 hours/week (8 hours/day, 5 days/week;
and 24 hours/day) using all three modeling approaches (Multistage modeling and both Model
Averaging approaches Frequentist Version 2.6 and Bayesian Version 3.0) are depicted in Table
3-6. These BMCLhec values represent the 95% lower confidence limit estimate of the occupational
exposure concentration expected to produce a l-in-10 (i.e., 10% BMR) or l-in-1,000 (i.e., 0.1%
BMR) lifetime extra (ER) or added risk (AR) of lung cancer, due to the different BMR values they
are not directly comparable. The BMCL values were selected as the POD for the inhalation unit
risk (IUR) value and the dermal slope factor because they reflect the statistical variability of the
data and in consistent with EPA BMD Guidance (U.S. EPA. 2012a). Although data suggest a
MMOA, the exact mode of action of 1-BP-induced tumorigenesis is not known. In the absence of
more definitive knowledge regarding the MOA of 1-BP, the inhalation unit risk and dermal slope
factor were calculated using the default linear approach i.e., IUR = BMR BMCL and rounded to
1 significant figure. The IURs are shown in Table 3-6 and the dermal cancer slope factors are
shown in Table 3-7. While the BMCLs are not directly comparable because of different BMRs the
IUR incorporate the BMR and can be compared.
Table 3-6. Inhalation Unit Risk (IUR) for Humans Exposed via Inhalation Based on
Combined Alveolar/Bronchiolar Adenomas or Carcinomas Observed in Female Mice
Modeling Approach
BMR
BMCLhec
(ppm)
IUR
(per ppm)
IUR
(per jig/m3)
Human Exposures 40 hours/week (8 hours/day, 5 days/week)
Multistage Model, ER
10%
25
4 x 10"3
8 x 10"7
Frequentist Model-Averaging, Version 2.6, AR
0.1%
0.3
3 x 10"3
7 x 10"7
Bayesian Model-Averaging, Version 3.0, ER
10%
18
6 x 10"3
1 x 10"6
Human Exposures 24 hours/day
Multistage Model, ER
10%
16
6 x 10"3
1 x 10"6
Frequentist Model-Averaging, Version 2.6, AR
0.1%
0.19
5 x 10"3
1 x 10"6
Bayesian Model-Averaging, Version 3.0, ER
10%
12
9 x 10"3
2 x 10"6
Page 226 of 486
-------
Table 3-7. Cancer Slope Factor for Humans Exposed via Dermal Contact Extrapolated from
Combined Alveolar/Bronchiolar Adenomas or Carcinomas Observed in Female Mice
Modeling Approach
BMR
BMDLhed
(mg/kg-day)
Slope Factor
(per mg/kg-day)
Multistage Model, ER
10%
17
6 x 10"3
Frequentist Model-Averaging, Version 2.6, AR
0.1%
0.21
5 x 10"3
Bayesian Model-Averaging, Version 3.0, ER
10%
13
8 x 10"3
Overall, the IURs and dermal slope factors calculated by all three modeling approaches (Multistage
modeling and both Model Averaging approaches Frequenstist Version 2.6 and Bayesian Version
3.0) are nearly the same. The model averaging approaches can be used to assess the impact of
model uncertainty and the similar results suggest model uncertainty is not significantly impacting
the IUR or the slope factor. Therefore the IURs and cancer slope factor using the multistage
modeling are used in cancer risk estimate calculations below consistent with EPA guidance EPA's
Guidelines for Carcinogen Risk Assessment (U.S. EPA 2005a)).
The IUR and dermal slope factor were used in EPA's risk evaluation to estimate extra cancer risks
for the inhalation and dermal occupational exposure scenarios. There is high confidence in the IUR
and the dermal slope factor because they were based on high quality animal data. EPA did not use
the IUR or dermal slope factor to calculate the theoretical cancer risk associated with a single
(acute) inhalation/or dermal exposure to 1-BP. Published methodology for extrapolating cancer
risks from chronic to short-term exposures includes the caveat that extrapolation of lifetime
theoretical extra cancer risks to single exposures has great uncertainties (NRC. 2001).
As NRC (2001) explains, "There are no adopted state or federal regulatory methodologies for
deriving short-term exposure standards for workplace or ambient air based on carcinogenic risk,
because nearly all carcinogenicity studies in animals and retrospective epidemiologic studies have
entailed high-dose, long-term exposures. As a result, there is uncertainty regarding the
extrapolation from continuous lifetime studies in animals to the case of once-in-a-lifetime human
exposures. This is particularly problematical, because the specific biologic mechanisms at the
molecular, cellular, and tissue levels leading to cancer are often exceedingly diverse, complex, or
not known. It is also possible that the mechanisms of injury of brief, high-dose exposures will
often differ from those following long-term exposures. To date, U.S. federal regulatory agencies
have not established regulatory standards based on, or applicable to, less than lifetime exposures to
carcinogenic substances."
Thus, EPA risk evaluation for 1-BP does not estimate extra cancer risks for acute exposures
because the relationship between a single short-term exposure to 1-BP and the induction of cancer
in humans has not been established in the current scientific literature.
3.2.8.3 Potentially Exposed or Susceptible Subpopulations
Factors affecting susceptibility examined in the available studies on 1-BP include lifestage, gender,
genetic polymorphisms, race/ethnicity, preexisting health status, lifestyle factors, and nutrition
Page 227 of 486
-------
status. The PECO statement in the problem formulation in June, 2018 (U.S. EPA. 2018c) includes
"potentially exposed or susceptible subpopulations such as infants, children, pregnant women,
lactating women, women of child bearing age" as "subpopulations" for the 1-BP Risk Evaluation.
These susceptible subpopulations were considered against the available 1-BP specific data. Women
of reproductive age, pregnant women and their offspring (fetal and postnatal) were identified as
susceptible subpopulations based on the non-cancer effects associated with 1-BP exposure in
rodent studies (WIL Research. 2001). A prenatal developmental toxicity study and a two-
generation reproductive toxicity study in rats exposed to 1-BP via the inhalation route reported
decreased live litter size (WIL Research. 2001). postnatal survival (Furuhashi et al.. 2006). pup
body weight, brain weight and skeletal development (Huntingdon Life Sciences. 1999).
(Huntingdon Life Sciences. 2001); (WTL Research. 2001). No epidemiological studies on the
developmental effects of 1-BP exposure were identified in the literature. Since effects were
observed in animals after gestational and postnatal exposure, pregnant women, and their offspring
were identified as susceptible subpopulations; however, there is some uncertainty about the critical
window for increased susceptibility to 1-BP exposure.
Other data on the noncancer effects of 1-BP exposure were reviewed to identify potential
susceptible subpopulations. A two-generation reproduction study in rats reported adverse effects on
male and female reproductive parameters (WIL Research. 2001) such as, significant increases in
post-implantation loss (pre-implantation loss could not be determined because of a lack of data on
the number of primordial follicles), reduced fertility in F0 females, and decreased mating indices,
and increased estrous cycle length and pregnancy loss. In F0 males, statistically significant changes
in reproductive endpoints included decreased absolute prostate and epididymal weights, decreased
sperm motility, and decreased mating and fertility indices (WIL Research. 2001). These findings
are supported by other studies (NTP. 2011b; Oin et al.. 2010; Liu et al.. 2009; Yu et al.. 2008;
Banu et al.. 2007; Yamada et al.. 2003; WIL Research. 2001; Ichihara et al.. 2000a). suggesting
that males of reproductive age represent another susceptible subpopulation for 1-BP exposure.
The primary metabolic pathways identified for 1-BP involve cytochrome P450 mediated oxidation
(CYP2E1) and glutathione conjugation reactions. Genetic polymorphisms and interindividual
variability in the expression and function of CYP2E1 have been linked to altered disease
susceptibility (Neafsev et al.. 2009) (Trafalis et al.. 2010). Although there are uncertainties in the
available data, chronic exposure to CYP2E1 inducers (e.g., ethanol, isoniazid), may increase the
probability of developing malignancy, especially for carriers of certain CYP2E1 alleles (Trafalis et
al.. 2010). Pre-existing health conditions, including alcoholism and diabetes also induce CYP2E1
activity, thereby enhancing susceptibility to the adverse effects of 1-BP exposure.
Additional susceptibility factors not explicitly quantified in the hazard assessment are expected to
be accounted for through the use of a 1 Ox UF to account for human variability, although EPA
acknowledges that certain subpopulations with particular disease states or genetic predispositions
may fall outside of the range covered by this UF. EPA can also not rule out that certain
subpopulations, whether due to very elevated exposure or biological susceptibility, may be at risk
for hazards that were not fully supported by the weight of the scientific evidence or could not be
quantified (e.g., immune and blood effects). However, in these circumstances, EPA assumes that
Page 228 of 486
-------
these effects are unlikely to occur at a lower dose than those more robust and sensitive endpoints
that underwent dose response analysis.
3.2.8.4 Points of Departure for Human Health Hazard Endpoints
Table 3-2 summarizes the hazard studies, health endpoints (PODs) by target organ/system, HECs
and UFs that are relevant for the risk evaluation of acute and chronic exposure scenarios. Table 3-8
lists the selected HECs/dermal HEDs by study type and duration category (acute vs. chronic)
carried forward for risk estimation. 0 contains a comprehensive summary table of adverse effects.
Inhalation HECs were converted to dermal HEDs using the following equation:
Dermal HED (mg/kg-day) = inhalation POD (ppm) x 5.031 mg/m3 / ppm x duration adjustment x
ventilation rate (m3) ^ body weight (kg)
where the inhalation HEC used was for a 40 hr work week (8 hrs / day, 5 days / week), the duration
adjustment was (6 hours / 8 hours x 7 days / 5 days) to account for differences between animal
exposure durations and expected human exposure durations, ventilation rate was 10 m3 (i.e.,
1.25 m3 per hour for 8 hours) and the body weight was 80 kg. The dermal exposure estimates
account for the fraction of 1-BP that is absorbed (see Section 2.3.1.23), therefore, an absorption
adjustment is not applied in the route-to-route extrapolation.
Page 229 of 486
-------
Table 3-8. HECs/Dermal HEDs Selected for Non-Cancer Effects for 1-BP
Exposure
Duration
for Risk
Analysis
Target
Organ/
System
Species
Route
of
Exposure
Range of
Doses or
Cone.1
(PPm)
Duration2
POD Type
(ppm)3
Effect
HEC4
Occu-
pational
(ppm)
HEC5
Consumers
(ppm)
Dermal
HED
(mg/kg-
day)"
Uncertainty
Factors (UFs)
for
Benchmark
MOE7
Reference
Data
Quality
Ranking8
CHRONIC
OCCUPATIONAL & CONSUMER
Liver
Rat
(male)
(n=25/
group)
Inhalation
100 to 750
6 hours/day during
pre-mating (> 70
days), throughout
mating, and until
sacrifice
BMCLio =
143.5
Increased
incidence of
vacuolization
of
centrilobular
hepatocytes
(Fo)'
150
36
95
UFS=1;
UFa=10;
UFh=10;
UFl=1;
Total UF=100
(WIL
Research.
200 n
High
(1.2)
Kidney
Rat
(female)
(n=25/
group)
Inhalation
100 to 750
6 hours/day during
pre-mating (> 70
days), throughout
mating, and until
GD 20; from PND 5
until weaning of
offspring (~PND
21)
BMCLio =
174
Increased
incidence of
pelvic
mineralizatio
11 (Fo)
180
44
115
UFS=1;
UFa=10;
UFh=10;
UFl=1;
Total UF=100
(WIL
Research.
200 n
High
(1.2)
Reproductive
System
Rat
(male)
(n=8-9)/
group
Inhalation
200 to 800
8 hours/day, 7
days/week for 12
weeks
BMCL1SD=
38
Decreased
absolute/
relative
seminal
vesicle
weight
53
13
33
UFS=1;
UFa=10;
UFh=10;
UFl=1;
Total UF=100
(Ichihara et
al.. 2000b 1
High
(1.7)
Develop-
mental Effects
(BMDS
nested
dichotomous
model,
NLogistic)
Rat
(n=25/
group)
Inhalation
100 to 500
6 hours/day during
pre-mating (> 70
days), throughout
mating, and until
GD 20 for the Fi
litters
BMCLi=
23
Post-
implantation
loss in F0
females
17
6
15
UFS=1;
UFa=10;
UFh=10;
UFl=1;
Total UF=100
(WIL
Research.
200 n
High
(1.2)
Develop-
mental Effects
(BMD
modeling)
Rat
(n=25/
group)
Inhalation
100 to 500
6 hours/day during
pre-mating (> 70
days), throughout
mating, and until
GD 20 for the Fi
litters
BMCL,=
41
Decreased
live litter
size (Fi) at
PND 0
31
10
27
UFS=1;
UFa=10;
UFh=10;
UFl=1;
Total UF=100
(WIL
Research.
200 n
High
(1.2)
Page 230 of 486
-------
Nervous
System
Rat
(male)
(n=5/
group)
Inhalation
10 to 1000
8 hours/day, 7
days/week for 3
weeks
BMCL1SD =
18.2
Decreased
time hanging
from a
suspended
bar (traction
time)
25
6
16
UFS=1;
UFa=10;
UFh=10;
UFl=1;
Total UF=100
(Honma et
al.. 20031
High
(1.6)
Exposure
Duration
for Risk
Analysis
Target
Organ/
System
Species
Route
of
Exposure
Range of
Doses or
Cone.1
(PPm)
Duration2
POD Type
(ppm)3
Effect
HEC4
Occu-
pational
(ppm)
HEC5
Consumer
(ppm)
Dermal
HED
(mg/kg-
day)"
Uncertainty
Factors (UFs)
for
Benchmark
MOE7
Reference
Data
Quality
Ranking8
ACUTE
OCCUPATIONAL & CONSUMER
Developmental
Effects
(BMDS
nested
dichotomous
model,
NLogistic)
Rat
(male)
(n=24-
25/
group)
Inhalation
100 to 500
6 hours/day during
pre-mating (> 70
days), throughout
mating, and until
sacrifice in males;
or until GD 20 and
from PND 5 until
27weaning of
offspring (~PND
21) in females
BMCLi=
23
Post-
implantation
loss in F0
females
17
6
11
UFS=1;
UFa=10;
UFh=10;
UFl=1;
Total UF=100
(WIL
Research.
200 n
High
(1.2)
Developmental
Effects
(BMD
modeling)
Rat
(male)
(n=24-
25/
group)
Inhalation
100 to 500
6 hours/day during
pre-mating (> 70
days), throughout
mating, and until
sacrifice in males;
or until GD 20 and
from PND 5 until
weaning of
offspring (~PND
21) in females
BMCL,=
41
Decreased
live litter
size (Fi)
31
10
19
UFS=1;
UFa=10;
UFh=10;
UFl=1;
Total UF=100
(WIL
Research.
200 n
High
(1.2)
Control concentrations are not included in the table.
2 Acute exposures defined as those occurring within a single day. Chronic exposures defined as 10% or more of a lifetime (U.S. EPA. 2011).
3POD type can be NOAEL, LOAEL, or BMCL. For BMCLs, the subscript indicates the associated BMR. The BMRs are a percentage relative deviation (e.g., 10%
relative deviation BMCLio) or 1 standard deviation change (BMCLisd) from the mean for continuous data. Post-implantation loss was modeled using the NLogistic
model.
4 HECs/dennal HEDs are adjusted from the study conditions by the equation HECexresp = POD x duration adjustment x DAF. The DAF is the ratio of blood:gas
partition coefficients (animal:human). For 1-BP, the blood:air partition coefficient for rats is greater than that for humans, so a default ratio of 1 is applied (U.S. EPA.
1994). For chronic exposure the duration adjustment was (hours per day exposed ^ 8) x (days per week exposed ^ 5) to reflect a 40-hour work week and for acute
exposure the duration adjustment was (hours per day exposed 8). All endpoints used the chronic exposure duration adjustment except for the acute developmental
endpoints of decreased live litter size (Fi) at PND 0 and post-implantation loss as described above in Section 3.2.8.1. The differences in the HECs between the
Page 231 of 486
-------
occupational and consumer exposures are due to the baseline used for the duration adjustment of acute occupational and consumer exposures; occupational exposures
was 8 hours/day, and consumer exposures was 24 hours/day (see next footnote). HECs/dermal HEDs are rounded to two significant digits.
5HEC for chronic consumer exposures is adjusted to 24 hours per day, 7 days per week and HEC for acute consumer exposures is adjusted to 24 hours per day.
6The dermal HEDs for dermal exposures were extrapolated from the inhalation PODs in mg/kg-day using a duration adjustment, human ventilation rate and human
body weight.
7UFS = subchronic to chronic UF (default value = 10); UFA = interspecies UF (default value of 10); UFH = intraspecies UF (default value = 10); UFL = LOAEL to
NOAEL UF (default value = 10) (U.S. EPA. 2002). Rationale for selection of specific UF values used to calculate the benchmark MOE for the key studies used in risk
is presented in Section 4.2.1. Narratives explaining overall UF determinations are provided in Section 3.2.8.1.
* BMD modeling did not adequately fit the variance in the data so the LOAEL is presented
8Data Quality Criteria Ranking: High > = 1 and < 1.7; Medium >= 1.7 and < 2.3; Low >=2.3 and <=3; The numbers in parentheses reflect the score associated with the
ranking. Lower scores reflect higher quality studies. Higher scores, reflect lower quality studies.
Page 232 of 486
-------
3.2.8.5 Strength, Limitation, and Uncertainty of the Hazard Identification and
Selection of PODs for Dose-Response Assessment
Limited toxicological data is available by the oral route, and no repeated-dose toxicity studies by
the dermal route were identified on 1-BP. Although the oral repeated-dose toxicity studies are
insufficient for a quantitative dose-response assessment, data from these studies were used as
qualitative support in the weight of the scientific evidence for nervous system effects (see Section
3.2.5.5 and Appendix J), suggesting that, at least for the nervous system endpoints, the delivery of
1-BP via the inhalation- {i.e., pulmonary/systemic circulation) and oral- {i.e., portal circulation)
routes of exposure results in comparable toxic endpoints. EPA chose to derive dermal HEDs for
dermal exposures by extrapolating from the inhalation route for systemic endpoints {i.e., not point
of contact effects). None of the key endpoints for 1-BP (liver, kidney, reproductive, developmental
and nervous system effects) were considered point of contact therefore, all were used for route-to-
route extrapolation. The route-to-route extrapolations enabled EPA to estimate applied dermal
PODs. Since physiologically based pharmacokinetic/ pharmacodynamic (PBPK/PD) models that
would facilitate route-to-route extrapolation have not been identified, there is no relevant kinetic or
metabolic information for 1-BP that would facilitate development of dosimetric comparisons, and
the studies by the oral route were insufficient for quantitative dose-response assessment, EPA
chose to derive dermal HEDs for dermal exposures by extrapolating from the inhalation PODs.
However, the inhalation studies were performed by whole body exposure, rather than nose only
exposure, which may have led to additional dosing by the oral and dermal routes of exposure, due
to deposition on fur and the grooming behavior of rodents, resulting in uncertainty of actual dose
received. It should be noted that EPA was unable to conclude with certainty that comparable toxic
endpoints would be associated with the dermal route of exposure, considering the expected
quantitative ADME differences and the absence of an adequate PBPK model. Notwithstanding
these uncertainties, EPA considered this approach appropriate considering the comparable toxic
endpoints identified in the available repeated-dose oral/inhalation toxicity studies and the
uncertainty with the putative toxicant {i.e., 1-BP or a metabolite(s)).
Overall there is high confidence in all endpoints selected as PODs for both acute and chronic exposure.
Endpoints selected for PODs for both acute and chronic exposure scenarios were derived from three studies,
(WIL Research. 2001). (Ichihara et al.. 2000b'). and (Honma et al.. 2003). These studies were selected
because they all scored High in data evaluation, followed OECD guidance and Good Laboratory Practice,
and were of longer duration with effects observed more consistently than other high-quality studies that
were evaluated. In addition, these endpoints were identified as the most robust and sensitive endpoints
relevant to acute and chronic exposures and were incidentally, also the lowest available PODs. The NOAEC
or LOAECs from these studies were refined with BMD modeling in order to obtain more precise POD
values that were used to derive corresponding HECs/dermal HEDs and uncertainty factors. BMD modeling
results always contain some level of uncertainty, and various factors such as model fit and BMR selection
may have a large effect on the final POD value. The PODs from all three studies could be fit into BMD
modeling, thereby reducing the uncertainty factors {i.e., UFl = 1) used in deriving the benchmark MOE.
EPA believes that the selected PODs best represent the hazards associated with 1-BP for quantitative risk
estimation.
Page 233 of 486
-------
EPA considers some developmental toxicity endpoints observed in a repeat dose developmental
toxicity study applicable to acute exposures. While there is some uncertainty surrounding this
consideration because the precise critical exposure window is unknown, multiple publications
suggest that some developmental effects (e.g., decreased live litter size and increased post-
implantation loss) may result from a single exposure during a critical window of development. In
this risk evaluation, effects following acute exposures to 1-BP included decreased live litter size
and increased post implantation loss (WIL Research. 2001). These specific developmental effects
were considered the most sensitive HECs/dermal HEDs derived for an acute exposure duration,
and are considered to be biologically relevant to the potentially exposed or susceptible
subpopulation (i.e., adults of reproductive age and their offspring). Further support for using this
endpoint for acute (short-term) exposures is the fact that the male and female reproductive effects
(in the Fo males and females) collectively contributing to the decreases in live litter size, all
occurred within a short window of exposure between ovulation and implantation. While exposures
during other lifestages (such as in childhood) may cause similar or related effects, without specific
information on the mechanism of action or developmental windows of sensitivity for these specific
developmental effects, there are uncertainties in extrapolating these effects for other lifestages in
order to refine dose estimates for these additional lifestages.
Page 234 of 486
-------
4 RISK CHARACTERIZATION
4.1 Environmental Risk
EPA integrated relevant pathways of environmental exposure with available environmental hazard
data to estimate risk to environmental receptors. EPA used estimated exposure values calculated
from E-FAST and monitored data from TRI, as well as aquatic hazard values based on reasonably
available hazard data to perform a quantitative screening-level determination of risks to aquatic
species from acute and chronic exposures to 1-BP using the RQ method. EPA's approach is
expected to represent a high-end estimate of aquatic exposure.
High volatility (Vapor Pressure= 110 mm Hg and Henry's Law constant of 7.3 x 10"3 atm-
m3/mole), and a consideration of the conditions of use of the chemical, indicates that 1-BP will
only be present in terrestrial environmental compartments as a transient vapor. No specific
conditions of use were identified that resulted in systematic, significant airborne exposures that
overlap with terrestrial habitats, so this is not a relevant route of exposure for 1-BP under the
conditions of use of this risk evaluation. Additionally, 1-BP is not expected to bioaccumulate
(BAF=12; BCF=11, see Table 2-1); therefore, exposure to terrestrial species through ingestion of
prey is negligible. No further analysis of risks to terrestrial receptors was carried out as part of this
final risk evaluation as risks from these exposure pathways are not expected.
4,1,1 Aquatic Pathways
The purpose of the environmental risk characterization is to discuss whether there are exceedances
of the concentrations of concern for the aquatic environment from levels of 1-BP found in surface
water taking into consideration fate properties, relatively high potential for release, and the
availability of environmental monitoring data and hazard data. Based on a qualitative assessment
of the physical-chemical properties and fate of 1-BP in the environment, EPA did not identify risk
concerns for sediment-dwelling aquatic organisms. Using a quantitative comparison of hazards and
exposures for aquatic organisms, EPA calculated risks to water-column dwelling aquatic species.
The results of both of these analyses are presented below. The environmental risk of 1-
bromopropane is characterized by calculating risk quotients or RQs (U.S. EPA. 1998a)
(Barnthouse et al.. 2008); the RQ is defined as:
RQ = Environmental Concentration/Effect Level
To determine the risk of 1-BP to aquatic species using risk quotients (RQs) method., the
"environmental concentration" represents the modeled exposure value calculated by E-FAST as
described below, while the "effect level" represents the aquatic COCs presented in Table 4-1. 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. If the RQ is below 1, the
exposure is less than the effect concentration.
As described in greater detail in Section 3.1, the acute and chronic concentrations of concern
(COCs) for aquatic species (shown in Table 4-1) were calculated based on the results of the high
Page 235 of 486
-------
quality study (Geiger et al.. 1988). After selecting the lowest toxicity values, an assessment factor
(AF) is applied according to EPA methods (Suter. 2016) (U.S. EPA 2012e) (U.S. EPA 2013b)37.
Table 4-1. Concentrations of Concern (COCs) for Environmental Toxicity as Described in
Section 3.1.5
Environmental
Toxicity
Endpoint
Data Source
Concentration of
Concern (COC)
Acute Toxicity,
aquatic organisms
96-hour Fish LCso
(Geiseret al.. 1988)
13,460 ng/L
Algae ECso
ECOSAR (v.2.0)
3,320 ng/L
Clironic Toxicity,
aquatic organisms
Fish Clironic Value*
(Geiseret al.. 1988)
673 ng/L
Daphnia ChV
ECOSAR (v.2.0)
426 ng/L
* = The fish chronic toxicity value is calculated by dividing the 96-hour fish LC50 by an acute to chronic ratio (ACR)
of 10; due to lack of clironic-duration test data for fish.
As described in Appendix H, EPA used the reported releases to water from EPA's Toxics Release
Inventory (TRI) to predict surface water concentrations near reported facilities for this Risk
Evaluation. To examine whether near-facility surface water concentrations could approach 1-BP's
aquatic concentrations of concern, EPA employed a first-tier screening-level approach, using
reasonably-available modeling tools and data, as well as conservative assumptions. EPA's
Exposure and Fate Assessment Screening Tool (U.S. EPA 2007) was used to estimate site-specific
surface water concentrations based on estimated loadings of 1-BP into receiving water bodies as
reported to TRI. E-FAST 2014 incorporates stream dilution using stream flow information
contained within the model. E-FAST also incorporates wastewater treatment removal efficiencies.
Wastewater treatment removal was assumed to be 0% for this exercise, as reported
loadings/releases are assumed to account for any treatment. As days of release and operation are
not reported, EPA assumed a range of possible release days (i.e., 1, 20, and 100 days/year). Refer
to the E-FAST 2014 Documentation Manual for equations used in the model to estimate surface
water concentrations (U.S. EPA. 2007). These estimated exposure concentrations were compared
with the reasonably available information for aquatic organisms to identify potential risks.
Table 4-2 summarizes the risk quotients (RQs) associated with acute and chronic exposures of 1-
BP, using the best available environmental hazard and release information, as well as using the
lowest available endpoint as predicted by ECOSAR modeling. As previously stated, an RQ below
1, indicates that the exposure concentrations of 1-BP is less than the concentrations that would
cause an effect to organisms in the aquatic pathways. The RQ values for risks from acute and
chronic exposure are <0.01 and 0.12, respectively based on the best available information, while
the RQs for acute and chronic exposure predicted with the lowest toxicity values predicted by
37 For fish and aquatic invertebrates (e.g., daphnia), the acute COC values are calculated by dividing the selected
environmental hazard endpoint by an AF of 5. For clironic COCs, and to calculate COCs for algae, an AF of 10 is
used.
Page 236 of 486
-------
ECOSAR are 0.02 and 0.18, respectively. These values indicate that risks are not identified for
aquatic receptors based on the conditions of use in this final risk evaluation.
Table 4-2. Calculated Risk Quotients (RQs) for 1-BP
Data Source
Concentrations of
Concern (CoC)
Maximum
Concentration
RQ
Acute
Scenario
(Geiseret al.. 1988)
13,460 ng/L
78 ng/L
<0.01
ECOSAR (v2.0)
3,320 ng/L
0.02
Chronic
Scenario
(Geiseret al.. 1988)
673 ng/L
0.12
ECOSAR (v2.0)
426 ng/L
0.18
For environmental release pathways, EPA quantitatively evaluated surface water exposure to
aquatic species. As explained in Section 2.1, 1-BP is not expected to sorb strongly to sediment or
soil. If present in biosolids, 1-BP would be expected to associate with the aqueous component
and/or volatilize to air as biosolids are applied to soil and allowed to dry. 1-BP is expected to
volatilize readily from dry soil and surfaces due to its vapor pressure (high volatility (vapor
pressure= 110 mm Hg at 20°C; Henry's law constant of 7.3X10"3 atm-m3/mole, see Table 1-1). 1-
BP has demonstrated moderate toxicity to aquatic organisms, and overall the exposures to surface
water from biosolids are estimated to be below concentrations of concern for these taxa. Therefore,
no quantitative analysis for risks to aquatic organisms from biosolids is necessary as exposures
from this pathway are expected to be negligible.
No sediment monitoring data for 1-BP are reasonably available, but physical-chemical
characteristics such as a high vapor pressure =110 mm Hg at 20°C and Henry's law constant of
7.3X10"3 atm-m3/mole (see Table 1-1) suggest that 1-BP is expected to quickly volatilize from
water and resultingly be present in very limited amounts in aquatic environments. Physical-
chemical properties input to EPISuite indicate that 1-BP will volatilize from a model river with a
half-life on the order of an hour and from a model lake on the order four days. Although
volatilization is expected to be rapid, a Level III Fugacity model predicts that when 1-BP is
continuously released to water, 80% of the mass will be in water 19% in air due in part to its water
solubility, while only <1% is predicted to transition to aquatic sediment. Intermittent releases of 1-
BP are not expected to result in long-term presence in the aquatic compartment. Chronic exposure
is only a likely scenario for environments near continuous direct release sites. 1-BP in sediment is
expected to be in the pore water rather than sorbed to the sediment solids based on a high water
solubility (2.4 g/L) and low log Koc (1.6). Overall, because 1-BP is expected to be present in
higher concentrations in pore water than sediments, sediment-dwelling organisms are not expected
to be exposed to a greater concentration of 1-BP than aquatic organisms. Furthermore, sediment is
not expected to be a source of 1-BP to overlying surface water, so additional risk concerns to these
sediment-dwelling organisms are not expected.
Page 237 of 486
-------
4.2 Human Health Risk
l-BP exposure is associated with a variety of cancer and non-cancer effects deemed relevant to
humans for risk estimations for the acute and chronic scenarios and populations addressed in this
risk evaluation. Based on a weight of the scientific evidence analysis of the reasonably available
toxicity studies from rats and humans, these effects include liver toxicity, kidney toxicity,
reproductive toxicity, developmental toxicity and neurotoxicity. The rationale for using the range of
toxic effects for chronic exposures is based on the fact that relatively low dose, short term/sub-
chronic exposures can result in long-term adverse consequences. The adverse developmental
effects are also deemed important for risk estimation for the acute exposure scenarios and
populations addressed in this risk evaluation. The rationale for using l-BP associated
developmental effects for evaluating risks associated with acute exposures is based on the
understanding that a single exposure during a critical window of vulnerability can adversely impact
the conceptus. l-BP is carcinogenic in animals. EPA derived an IUR and dermal slope factor based
on lung tumors in female mice to evaluate cancer risk.
4.2.1 Risk Characterization Approach
Table 4-3, Table 4-4, and Table 4-5 show the use scenarios, populations of interest and
toxicological endpoints used for acute and chronic exposures, respectively.
Table 4-3. Use Scenarios, Populations of Interest and Toxicological Endpoints for Assessing
Occupational Risks Following Acute Exposures to l-BP
Populations And
Toxicological Approach
Occupational Use Scenarios of l-BP
Population of Interest and
Exposure Scenario
Workers:
Adult male and female1 (>16 years old) who directly handle l-BP as part of their job
function (typically 8-hr work day).
Occupational Non-user:
Adult male and female1 (>16 years old) who do not directly handle l-BP, but who are
potentially exposed by being present in the surrounding work area of building (typically
8-hr work day).
Health Effects of Concern
Concentration and Time
Duration
Non-Cancer Health Effects: Decreased live litter size (Fi) usins BMD modeline; Post-
iniDlantation loss in Fnfemales usins NLoeistic modeline (WIL Research 2001)2
1. Non-cancer hazard values or Point of Departures (PODs; BMD): 8-hr HEC:
31 ppm; 24-hr dermal HED: 19 mg/kg-day
2. Non-cancer hazard values or Point of Departures (PODs; NLogistic): 8-hr HEC: 17
ppm; 24-hr dermal HED: 11 mg/kg-day
Cancer Health Effects: Cancer risks following acute exposures were not estimated.
Relationship is not known between a single short-term exposure to l-BP and the
induction of cancer in humans.
Page 238 of 486
-------
Uncertainty Factors (UF) used
in Non-Cancer Margin of
Exposure (MOE) calculations
(UFS=1) x (UFA=10) x (UFH=10) x (UFL=1)3 = 100
Total UF=Benchmark MOE=100
Notes:
includes pregnant women and adults of reproductive age.
2Thc risk assessment for acute exposures focused on the most sensitive life stage in humans, which is women and adults
of reproductive age and fetus (i.e., pregnant user) due to concerns for developmental effects. Developmental toxicity
effects were considered as the most sensitive health effect when compared to other potential acute effects (i.e.,
neurotoxicity).
3UFS=subchronic to chronic UF; UFA=interspecies UF; UFH=intraspecies UF; UFL=LOAEL to NOAEL UF
Table 4-4. Use Scenarios, Populations of Interest and Toxicological Endpoints for Assessing
Consumer Risks Following Acute/Chronic Exposures to 1-BP
Population and Toxicological
Approach
Consumer Use Scenarios of 1-BP (9 Scenarios)
Population of Interest
Women and adults of reproductive age1 Users (Youth 11-15, Youth 16-20, Adult 21
years and greater)
Bystander (Any age group (infant to elderly))
Exposure Scenario2:
Users, High-intensity use
95th percentile duration of use
95th percentile mass of product used
High weight fraction (amount of chemical in product)
Exposure Scenario2:
Users, moderate intensity use
50th percentile duration of use
50th percentile mass of product used
Mean/median weight fraction (amount of chemical in product)
Exposure Scenario2:
Users, low intensity use
10th percentile duration of use
10th percentile mass of product used
Low weight fraction (amount of chemical in product)
Population of Interest and Exposure
Scenario: Bystander
Women and adults of reproductive age non-users4 and individuals of multiple age
groups that are exposed to indirect 1-BP exposures by being in the rest of the
house.
Acute Health Effects of Concern,
Concentration and Time Duration
Non-Cancer Health Effects: Decreased live litter size (Fi) usins BMD modeline;
Post-iniDlantation loss in Fo females usins NLoeistic modeline (WIL Research.
2001)5
1. Non-cancer hazard values or Point of Departures (PODs; BMD): 24-hr HEC:
10 ppm; 24-hr HED: 19 mg/kg-day
2. Non-cancer hazard values or Point of Departures (PODs; NLogistic): 24-hr
HEC: 6 ppm; 24-hr HED: 11 mg/kg-day
Cancer Health Effects: Cancer risks following acute exposures were not estimated.
Relationship is not known between a single short-term exposure to 1-BP and the
induction of cancer in humans.
Page 239 of 486
-------
Population and Toxicological
Approach
Consumer Use Scenarios of 1-BP (9 Scenarios)
Chronic Non-Cancer Health Effects of
Concern,
Concentration and Time Duration
Non-Cancer Health Effects:
1. Non-cancer health effects for inhalation and dermal exposures: A range of
possible chronic non-cancer adverse effects in liver, kidney, nervous system,
reproductive system and developmental effects (including 2 modeling approaches
for developmental effects)
2. Non-cancer hazard values or Point of Departures (PODs): The most robust and
sensitive POD (i.e., 24-hr HEC expressed in ppm; 24-hr dermal HED expressed as
mg/kg-day) within each health endpoint domain. See Table 3-2.
Cancer Health Effects of Concern,
Concentration and Time Duration
Cancer Health Effects:
1. Cancer health effects for inhalation exposures: Data for luns tumors (NTP.
201 la) in female mice was selected as the POD considered protective for the other
tumor types.
2. Cancer Inhalation Unit Risk (IUR): See Table 3-6 for IUR values using model
averaging and multistage modeling approaches; the IUR (24 hrs/day) using the
multistage modeling are used in the cancer risk estimate calculations.
Uncertainty Factors (UF) used in Non-
Cancer Margin of Exposure (MOE)
calculations
(UFS=1) x (UFA= 10) x (UFH=10) x (UFL=1)6 = 100
Total UF=Benchmark MOE=100
Notes:
'The risk assessment for acute exposures focused on the most sensitive life stage in humans, which is women and adults of
reproductive age and fetus (i.e., pregnant user) due to concerns for developmental effects.
2E-FAST/CEM provided the 24-hr acute exposure estimate and the HECs were adjusted to 24-lirs.
3It is assumed no substantial buildup of 1-BP in the body between exposure events due to 1-BP's short biological half-life
(<2 hours).
4EPA believes that the users of these products are generally adults or youth (11 -20 yrs of age), but any age group may be a
bystander living in the house where product was used.
5The risk assessment for acute exposures focused on developmental toxicity effects as the most sensitive health effect when
compared to other potential acute effects (i.e., neurotoxicity).
6UFS=subchronic to chronic UF; UFA=interspecies UF; UFH=intraspecies UF; UFL=LOAEL to NOAEL UF
Page 240 of 486
-------
Table 4-5. Use Scenarios, Populations of Interest and Toxicological Endpoints for Assessing
Occupational Risks Following Chronic Exposures to 1-BP
Populations and Toxicological
Approach
Occupational Use Scenarios of 1-BP
Population of Interest and Exposure
Scenario
Workers:
Adult male and female1'2 (>16 years old) who directly handle 1-BP as part of their job
function (typically 260 days per year over 31 working years, see the 1-BP
Supplemental File: Supplemental Information on Occupational Exposure Assessment
(EPA. 2019f)).
Occupational Non-user:
Adult male and female1'2 (>16 years old) who do not directly handle 1-BP, but who are
potentially exposed by being present in the surrounding work area of building
(typically 260 days per year over lifetime working years, see the 1-BP Supplemental
File: Supplemental Information on Occupational Exposure Assessment (EPA. 2019f)).
Non-Cancer Health Effects:
1. Non-cancer health effects for inhalation and dermal exposures: A range of
possible chronic non-cancer adverse effects in liver, kidney, nervous system,
reproductive system and developmental effects (including 2 modeling approaches
for developmental effects)
2. Non-cancer hazard values or Point of Departures (PODs): The most robust and
sensitive POD (i.e., 8-hr and 24-hr HEC expressed in ppm; 24-hr dermal HED
expressed as mg/kg-day) within each health endpoint domain. See Table 3-2.
Health Effects of Concern,
Concentration and Time Duration
Cancer Health Effects:
1. Cancer health effects for inhalation and dermal exposures: Data for lung tumors
(NTP. 2011a) in female mice was selected as the POD considered orotective for
the other tumor types.
2. Cancer Inhalation Unit Risk (IUR): See Table 3-6 and Table 3-7 for IUR values
and dermal slope factors using model averaging and multistage modeling
approaches; the IUR (40 lirs/wk and 24 hrs/day) and dermal cancer slope factor
using the multistage modeling are used in the cancer risk estimate calculations.
Uncertainty Factors (UF) Used in
Non-Cancer Margin of Exposure
(MOE) calculations
Study- and endpoint-specific UFs. See Table 3-2.
Notes:
includes pregnant women and adults of reproductive age.
2Thc risk assessment for chronic exposures for developmental effects focused on the most sensitive life stage in humans,
which are women and adults of reproductive age and fetus (i.e., pregnant worker). For other health effects (e.g., liver,
kidney, etc.), healthy female or male workers were assumed to be the population of interest.
EPA applied a composite UF of 100 for the acute and chronic inhalation benchmark MOE, based
on the following considerations (see Section 3.2.8.1.3 for full details):
Page 241 of 486
-------
• An interspecies uncertainty/variability factor of 10 (UFa) was applied for animal-to-human
extrapolation. 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, a portion of the toxicokinetic uncertainty may be accounted for by the
calculation of an HEC and application of a dosimetric adjustment factor as outlined in the RfC
methodology (U.S. EPA. 1994); however, an UFa of 10 is retained to account for additional
toxicokinetic differences that remain unaccounted; 1-BP is irritating to the respiratory tract and
rodents exhibit physiological responses (such as reflex bradypnea) that differ from humans and
may alter uptake due to hyper- or hypoventilation, resulting in decreased internal dose relative
to the applied concentration. Therefore, an UFa of 10 is retained to account for toxicokinetic
differences (OECD 39);
• A default intraspecies uncertainty/variability factor (UFh) of 10 was applied to account for
variation in sensitivity within human populations due to limited information regarding the
degree to which human variability {i.e., gender, age, health status, or genetic makeup) may
impact the disposition of or response to, 1-BP;
• Interindividual variability in the expression and functional capacity of CYP2E1 has been
observed (Neafsev et al.. 2009) and genetic polymorphisms in CYP2E1 expression have been
linked to altered disease susceptibility (Trafalis et al.. 2010); and,
• A LOAEL-to-NOAEL uncertainty factor (UFl) of 1 was applied because BMD modeling was
used to derive the HEC.
• A subchronic-to-chronic uncertainty factor (UFs) of 1 was applied because the studies used for
risk estimation either were of chronic duration or the database did not suggest increased
toxicity at longer durations (neurotoxicity).
Acute and chronic MOEs (MOEaCute or MOEchronic) were used in this evaluation to estimate non-
cancer risks using Equation 4-1.
Equation 4-1. Equation to Calculate Non-Cancer Risks Following Acute or Chronic
Exposures Using Margin of Exposures
Non — cancer Hazard value {POD)
MOEacute or chronic 7r ^
Human Exposure
Where:
MOE = Margin of exposure (unitless)
Hazard value (POD) = HEC (ppm)
Human Exposure = Exposure estimate (in ppm) from occupational or consumer exposure
assessment. ADCs were used for non-cancer chronic scenarios and acute concentrations were used
for acute scenarios (see Section 2.3).
Page 242 of 486
-------
EPA used margin of exposures (MOEs)38to estimate risks associated with acute or chronic non-
cancer scenarios based on the following:
• The highest quality HECs/dermal HEDs within each health effects domain reported in the
literature;
• The endpoint/study-specific UFs applied to the HECs/dermal HEDs per EPA Guidance (U.S.
EPA.2002); and
• The exposure estimates calculated for 1-BP uses examined in this risk evaluation.
MOE estimates allow for the presentation of a range of risk estimates. The occupational exposure
scenarios considered both acute and chronic inhalation and dermal exposures. All consumer uses
considered only acute inhalation and dermal exposure scenarios. Different adverse endpoints were
used based on the expected exposure durations. For non-cancer effects, risks for developmental
effects were evaluated for acute (short-term) exposures, whereas risks for other adverse effects
(toxicity to the liver, kidney, nervous system, developmental effects, and the reproductive system)
were evaluated for repeated (chronic) exposures to 1-BP.
For occupational exposure calculations, the 8 hr TWA was used to calculate MOE estimates for
acute and chronic exposures.
The total UF for each non-cancer POD was the benchmark MOE used to interpret the MOE risk
estimates for each use scenario. The MOE estimate was interpreted as a potential human health
concern if the MOE estimate was less than the benchmark MOE {i.e., the total UF). On the other
hand, the MOE estimate indicated negligible concerns for adverse human health effects if the MOE
estimate exceeded the benchmark MOE. Typically, the larger the MOE, the more unlikely it is that
a non-cancer adverse effect would occur.
MOE estimates were calculated for all of the studies per health effects domain that EPA considered
suitable for the risk evaluation of acute and chronic exposure scenarios in the work plan risk
assessment for 1-BP.
Extra cancer risks for repeated exposures to 1-BP were estimated using Equation 4-2. Estimates of
extra cancer risks should be interpreted as the incremental probability of an individual developing
cancer over a lifetime as a result of exposure to the potential carcinogen {i.e., incremental or extra
individual lifetime cancer risk).
Equation 4-2. Equation to Calculate Extra Cancer Risks
Risk = Human Exposure x IUR
38 Margin of Exposure (MOE) = (Non-cancer hazard value, POD) (Human Exposure). Equation 4-1 The benchmark
MOE is used to interpret the MOEs and consists of the total UF shown in Table 3-2. See 3.2.8.1 for an explanation of
the benchmark MOE.
Page 243 of 486
-------
Where:
Risk = Extra cancer risk (unitless)
Human exposure = Exposure estimate (LADC in ppm) from occupational exposure assessment
IUR = Inhalation unit risk (3 x 10"3 per ppm)
4.2,2 Occupational Inhalation Exposure Summary and PPE Use Determination by
OES
EPA considered the reasonably available data for estimating exposures for each OES. EPA also
determined whether air-supplied respirator use up to APF = 50 was plausible for those OES based
on expert judgement and reasonably available information. Table 4-6 presents this information
below, which is considered in the risk characterization for each OES in the following sections.
EPA did not evaluate respirator use for the following occupational scenarios:
• Dry Cleaning; Spot Cleaner, Stain Remover. Many dry cleaning shops are small, family -
owned businesses and are unlikely to have a respiratory protection program.
• Aerosol Spray Degreaser/Cleaner: EPA believes many aerosol degreasing activities occur in
commercial settings. For example, the aerosol degreasing model estimates worker exposure at
automotive brake servicing shops. Based on reasonably available information, EPA believes
workers at brake servicing shops are unlikely to wear respirators.
Table 4-6. Inhalation Exposure Data Summary and Respirator Use Determination
()ci'ii|>iilion;il
l'l\|)OMIIV
Scenario
Inhiihilioii
l'A|)OMIIV
\ppro;ich
Number
of Diilii
Points
Model I sod
Approach
lor OM s
Kcspiriilor
I so
liulusli'iiil or
ComiiKTciiil
OI.S
Manufacture
Monitoring
data
3 (8-hr
TWA)
N/A - monitoring
data only
N/A
(expected to
be negligible)
Assumed
respirator use
Industrial
Import
Modeling
N/A-
model
only
Tank Truck and
Railcar Loading
and Unloading
Release and
Inhalation
Exposure Model
N/A
(expected to
be negligible)
Assumed
respirator use
Industrial
Processing as a
Reactant
Modeling
N/A-
model
only
Assumed
respirator use
Industrial
Processing -
Incorporation
into
Formulation,
Mixture, or
Reaction
Product
Monitoring
data
11 (8-hr
TWA)
N/A - monitoring
data only
Monitoring
data
Assumed
respirator use
Industrial
Processing -
Incorporation
into articles
Modeling
N/A-
model
only
Tank Truck and
Railcar Loading
and Unloading
N/A
(expected to
be negligible)
Assumed
respirator use
Industrial
Page 244 of 486
-------
()ci'ii|>iilion;il
l'l\|)OMIIV
Scniiirio
Inhiihilioii
l'A|)OMIIV
Approach
Number
of Diilii
Points
Model I sod
Approiich
lor OM s
Kcspiriilor
l so
liulusli'iiil or
ComiiKTciiil
OI.S
Repackaging
Modeling
N/A-
model
only
Release and
Inhalation
Exposure Model
Assumed
respirator use
Industrial
Disposal,
Recycling
Modeling
N/A-
model
only
Assumed
respirator use
Industrial
Batch Vapor
Degreaser
(Open-Top)
Monitoring
data and
modeling
230 (8-hr
TWA)
Open-Top Vapor
Degreasing Near-
Field/Far-Field
Inhalation
Exposure Model
Monitoring
data and far-
field model
results
Assumed
respirator use
Industrial
Batch Vapor
Degreaser
(Closed-Loop)
Modeling
N/A-
model
only
Far-field
model results
Assumed
respirator use
Industrial
In-line Vapor
Degreaser
See Batch Vapor Degreaser (Open-Top)
Assumed
respirator use
Industrial
Cold Cleaner
Monitoring
data and
modeling
6 (8-hr
TWA)
Cold Cleaning
Near-Field/Far-
Field Inhalation
Exposure Model
Monitoring
data and far-
field model
results
Assumed
respirator use
Industrial
Aerosol Spray
Degreaser /
Cleaner
Monitoring
data and
modeling
7 (8-hr
TWA)
Brake Servicing
Near-Field/Far-
Field Inhalation
Exposure Model
Far-field
model results
Not expected
Commercial
Adhesive
Chemicals
(Spray
Adhesives)
Monitoring
data
228 (8-hr
TWA)
N/A - monitoring
data only
Monitoring
data
Assumed
respirator use
Commercial
Dry Cleaning
Monitoring
data and
modeling
14 (8-hr
TWA)
Dry Cleaning
Multi-Zone
Inhalation
Exposure Model
Monitoring
data and far-
field model
results
Not expected
Commercial
Spot Cleaner,
Stain Remover
Monitoring
data and
modeling
6 (8-hr
TWA)
Spot Cleaning
Near-Field/Far-
Field Inhalation
Exposure Model
Far-field
model results
Not expected
Commercial
THERMAX™
Installation
Modeling
N/A-
model
only
IECCU
Screening-
level model
analysis
Assumed
respirator use
Commercial
Other Uses
Not quantified
Industrial /
Commercial
4,2.3 Risk Characterization For Acute, Non-Cancer Inhalation Exposures
Non-cancer MOE estimates for acute inhalation and dermal exposures to 1-BP were derived for
both occupational scenarios and consumer scenarios. Cancer risk estimates for acute inhalation
exposures to 1-BP were not derived for occupational or consumer scenarios because the published
Page 245 of 486
-------
methodology for extrapolating cancer risks from chronic to short-term exposures includes the
caveat that extrapolation of lifetime theoretical extra cancer risks to single exposures has great
uncertainty CNRC. 2001).
The risk assessment for acute inhalation and dermal exposures used developmental toxicity data to
evaluate the risks following acute exposures with the TSCA condition of use scenarios identified
for 1-BP under the scope of this risk evaluation. EPA based its risk evaluation for the acute
exposure scenario on developmental toxicity {i.e., decreased live litter size, and increases in post-
implantation loss), the most robust and sensitive HEC/dermal HED identified for an acute exposure
duration (WIL Research. 2001). which is representative of potentially exposed or susceptible
subpopulation {i.e., adults of reproductive age and their offspring). For acute occupational
exposure scenarios, EPA did not assess risks to children who may be present in the workplace
{e.g., dry cleaners). Risk estimates were based on the most robust and sensitive endpoint, which is
applicable to pregnant women. EPA expected that risk estimates based on this endpoint are
protective of any other acute hazard that could be applicable to children lifestages. See Section
3.2.8.5 and 4.2.1 for additional discussion.
The risk assessment for acute exposures used the hazard value from the (WIL Research. 2001)
two-generation reproductive toxicity study to evaluate risks for each occupational and consumer
exposure scenario.
4.2.3.1 Acute Occupational Exposures
Non-cancer MOE estimates for acute occupational exposure scenarios are presented in Table 4-7
through Table 4-26. MOE estimates (HEC in ppm/exposure estimate in ppm; dermal HED
exposure estimate in mg/kg-day) that are below the Benchmark MOE (Total UF) are highlighted in
red. Where the sample size of the underlying exposure data is sufficiently large to calculate
statistics, the central tendency estimate is based on the 50111 percentile exposure level of the dataset,
while the high-end estimate is based on the 95th percentile exposure. See Section 2.3.1.2 for
detailed descriptions of central tendency and high-end estimates.
MOE estimates for worker respirator scenarios presented below are based on the level of APF
required to mitigate risk for all health domains (APF of 10, 25, or 50). For some occupational
conditions of use, respirators with an APF of 50 do not reduce worker exposure to levels where the
calculated MOE is greater than the benchmark MOE. The MOE estimates for these respirator
scenarios assume workers are properly trained and fitted on respirator use, and that they wear
respirators for the entire duration of the work activity where there is potential exposure to 1-BP. As
explained in Section 4.2.2, APFs were not applied to the dry cleaning, spot cleaning, and aerosol
degreasing scenarios because EPA assumes respirator use is unlikely for these conditions of use. In
addition, EPA does not evaluate respirator use for occupational non-users because they do not
directly handle 1-BP and are unlikely to wear respirators.
Page 246 of 486
-------
Table 4-7. Non-Cancer Risk Estimates for Acute Inhalation Exposures Following
Occupational Use of 1-BP in Manufacture Based on Monitoring Data (U.S.)
Health Effect, Endpoint and
Study
Acute
HEC
(ppm)
Exposure Level
Acute MOE
APF=10
Benchmark
MOE
Worker
ONU
Worker
Developmental Effects
Decreased live litter size (Fi)
(WIL Research. 2001)
31
Central tendency
344
N/A
3,444
100
High-end
115
N/A
1,148
Developmental Effects
Post-Implantation Loss (F0)
(WIL Research. 2001):
NLogistic Model
17
Central tendency
189
N/A
1,889
100
High-end
63
N/A
630
Note: Exposure monitoring was not performed for ONUs at this manufacturing facility. Based on the process and work
activity description, exposure to ONU is expected to be negligible.
Table 4-8. Non-Cancer Risk Estimates for Acute Inhalation Exposures Following
Occupational Use of 1-BP in Import, Repackaging, Processing as a Reactant, and Processing
- Incorporation into Articles Based on Modeling
Health Effect, Endpoint and Study
Acute
HEC
(ppm)
Exposure Level
Acute MOE
Benchmark
MOE
Worker
ONU
Developmental Effects
Decreased live litter size (Fi)
(WIL Research. 2001)
31
Central tendency
8,099
N/A
100
High-end
546
N/A
Developmental Effects
Post-Implantation Loss (F0)
(WIL Research. 2001); NLoeistic
Model
17
Central tendency
4,441
N/A
100
High-end
300
N/A
N/A - Not applicable. Because the model assumes tank truck and railcar loading/unloading occurs outdoors, EPA
expects ONU exposure to be negligible due to airborne concentration dilution in ambient air.
Table 4-9. Non-Cancer Risk Estimates for Acute Inhalation Exposures Following
Occupational Use of 1-BP in Processing - Incorporation into Formulation Based on
Monitoring Data
Health Effect, Endpoint and
Study
Acute
HEC
(ppm)
Exposure Level
Acute MOE
APF=50
Benchmark
MOE
Worker
ONU
Worker
Developmental Effects
Decreased live litter size (Fi)
(WIL Research. 2001)
31
Central tendency
4
200
215
100
High-end
113
Developmental Effects
Post-Implantation Loss (F0)
(WIL Research. 2001):
NLogistic Model
17
Central tendency
2
110
118
100
High-end
62
Page 247 of 486
-------
Table 4-10. Non-Cancer Risk Estimates for Acute Inhalation Exposures Following
Occupational Use of 1-BP in Batch Vapor Degreaser (Open-Top) Based on Monitoring Data
Health Effect, Endpoint and
Study
Acute
HEC
(ppm)
Exposure Level
Acute MOE
APF=50
Benchmark
MOE
Worker
ONU
Worker
Developmental Effects
Decreased live litter size (Fi)
(WIL Research. 2001)
31
Central tendency
5
310
231
100
High-end
1
67
31
Developmental Effects
Post-Implantation Loss (F0)
(WIL Research. 2001):
NLogistic Model
17
Central tendency
3
170
127
100
High-end
0.34
37
17
Table 4-11. Non-Cancer Risk Estimates for Acute Inhalation Exposures Following
Occupational Use of 1-BP in Batch Vapor Degreaser (Open-Top) Based on Modeling (Pre-
EC3)
Health Effect, Endpoint and
Study
Acute
HEC
(ppm)
Exposure Level
Acute MOE
APF=50
Benchmark
MOE
Worker
ONU
Worker
Developmental Effects
Decreased live litter size (Fi)
(WIL Research. 2001)
31
Central tendency
16
31
820
100
High-end
1
2
65
Developmental Effects
Post-Implantation Loss (F0)
(WIL Research. 2001):
NLogistic Model
17
Central tendency
9
17
450
100
High-end
1
1
36
aEC = Engineering Controls. Pre-EC = Modeling where no reduction due to engineering controls was assumed
Post-EC = Engineering controls such as LEV with 90% efficiency.
Table 4-12. Non-Cancer Risk Estimates for Acute Inhalation Exposures Following
Occupational Use of 1-BP in Batch Vapor Degreaser (Open-Top) Based on Modeling (Post-
EC3)
Health Effect, Endpoint and
Study
Acute
HEC
(ppm)
Exposure Level
Acute MOE
APF=25
Benchmark
MOE
Worker
ONU
Worker
Developmental Effects
Decreased live litter size (Fi)
(WIL Research. 2001)
31
Central tendency
164
312
4,099
100
High-end
13
23
324
Developmental Effects
Post-Implantation Loss (F0)
(WIL Research. 2001):
NLogistic Model
17
Central tendency
90
171
2,248
100
High-end
7
13
178
Page 248 of 486
-------
aEC = Engineering Controls. Pre-EC = Modeling where no reduction due to engineering controls was assumed
Post-EC = Engineering controls such as LEV with 90% efficiency.
Table 4-13. Non-Cancer Risk Estimates for Acute Inhalation Exposures Following
Occupational Use of 1-BP in Batch Vapor Degreaser (Closed-Loop) Based on Modeling
Health Effect, Endpoint and
Study
Acute
HEC
(ppm)
Exposure Level
Acute MOE
APF=10
Benchmark
MOE
Worker
ONU
Worker
Developmental Effects
Decreased live litter size (Fi)
(WIL Research. 2001)
31
Central tendency
820
1,561
8,199
100
High-end
65
115
648
Developmental Effects
Post-Implantation Loss (F0)
(WIL Research. 2001):
NLogistic Model
17
Central tendency
450
856
4,496
100
High-end
36
63
355
Table 4-14. Non-Cancer Risk Estimates for Acute Inhalation Exposures Following
Occupational Use of 1-BP in Cold Cleaner Based on Monitoring Data
Health Effect, Endpoint and
Study
Acute
HEC
(ppm)
Exposure Level
Acute MOE
APF=50
Benchmark
MOE
Worker
ONU
Worker
Developmental Effects
Decreased live litter size (Fi)
(WIL Research. 2001)
31
Central tendency
7
12
360
100
High-end
4
12
209
Developmental Effects
Post-Implantation Loss (F0)
(WIL Research. 2001):
NLogistic Model
17
Central tendency
4
7
198
100
High-end
2
7
115
Table 4-15. Non-Cancer Risk Estimates for Acute Inhalation Exposures Following
Occupational Use of 1-BP in Cold Cleaner Based on Modeling
Health Effect, Endpoint and
Study
Acute
HEC
(ppm)
Exposure Level
Acute MOE
APF=50
Benchmark
MOE
Worker
ONU
Worker
Developmental Effects
Decreased live litter size (Fi)
(WIL Research. 2001)
31
Central tendency
56
107
2,822
100
High-end
3
5
130
Developmental Effects
Post-Implantation Loss (F0)
(WIL Research. 2001):
NLogistic Model
17
Central tendency
31
59
1,548
100
High-end
1
2
71
Page 249 of 486
-------
Table 4-16. Non-Cancer Risk Estimates for Acute Inhalation Exposures Following
Occupational Use of 1-BP in Aerosol Spray Degreaser Based on Monitoring Data (Pre-ECa)
Health Effect, Endpoint and
Study
Acute
HEC
(ppm)
Exposure Level
Acute MOE
Benchmark
MOE
Worker
ONU
Developmental Effects
Decreased live litter size (Fi)
(WIL Research. 2001)
31
Central tendency
2
No data
100
High-end
1
No data
Developmental Effects
Post-Implantation Loss (F0)
(WIL Research. 2001):
NLogistic Model
17
Central tendency
1
No data
100
High-end
1
No data
Note: EPA did not identify exposure monitoring data for ONUs. EPA estimated exposure level for ONU through
modeling.
a EC = Engineering Controls.
Table 4-17. Non-Cancer Risk Estimates for Acute Inhalation Exposures Following
Occupational Use of 1-BP in Aerosol Spray Degreaser Based on Monitoring Data (Post-ECa)
Health Effect, Endpoint and
Study
Acute
HEC
(ppm)
Exposure Level
Acute MOE
Benchmark
MOE
Worker
ONU
Developmental Effects
Decreased live litter size (Fi)
(WIL Research. 2001)
31
N/A
(Single data point)
6
No data
100
Developmental Effects
Post-Implantation Loss (F0)
(WIL Research. 2001):
NLogistic Model
17
3
No data
100
Note: EPA did not identify exposure monitoring data for ONUs. EPA estimated exposure level for ONU through
modeling.
aEC = Engineering Controls. Post-EC = The vented booth scenario from Tech Spray study.
Table 4-18. Non-Cancer Risk Estimates for Acute Inhalation Exposures Following
Occupational Use of 1-BP in Aerosol Spray Degreaser Based on Modeling
Health Effect, Endpoint and
Study
Acute
HEC
(ppm)
Exposure Level
Acute MOE
Benchmark
MOE
Worker
ONU
Developmental Effects
Decreased live litter size (Fi)
(WIL Research. 2001)
31
Central tendency
5
282
100
High-end
1
33
Developmental Effects
Post-Implantation Loss (F0)
(WIL Research. 2001):
NLogistic Model
17
Central tendency
3
155
100
High-end
1
18
Page 250 of 486
-------
Table 4-19. Non-Cancer Risk Estimates for Acute Inhalation Exposures Following
Occupational Use of 1-BP in Dry Cleaning Based on Monitoring Data
Health Effect, Endpoint and
Study
Acute
HEC
(ppm)
Exposure Level
Acute MOE
Benchmark
MOE
Worker
ONU
Developmental Effects
Decreased live litter size (Fi)
(WIL Research. 2001)
31
Central tendency
1
3
100
High-end
1
2
Developmental Effects
Post-Implantation Loss (F0)
(WIL Research. 2001); NLoeistic
Model
17
Central tendency
1
1
100
High-end
0.34
0.82
For the dry cleaning condition of use, the MOE estimates for ONUs are expected to be protective
of children potentially present at dry cleaners because the modeled exposure concentrations for
children (as shown in Table 2-22) are lower than those for adult ONUs. In addition, the use of the
developmental toxicity endpoint for risk estimation is protective of any other acute hazards these
children may experience.
Page 251 of 486
-------
Table 4-20. Non-Cancer Risk Estimates for Acute Inhalation Exposures Following
Occupational Use of 1-BP in Dry Cleaning Based on Modeling (3rd Generation Machine)
Health Effect, Endpoint and
Study
Exposure
Acute MOE
Benchmark
MOE
Level
Spot
Cleaner
Machine & Finish
ONU
Developmental Effects
Decreased live litter size (Fi)
(WIL Research. 2001)
Central
tendency
7
1
11
100
High-end
3
0.33
3
Developmental Effects
Post-Implantation Loss (F0)
Central
tendency
4
1
6
100
(WIL Research. 2001); NLoeistic
Model
High-end
1
0.19
2
Studv: (WIL Research. 2001). Note: Based on acute HEC of 10 ddiii and 5.7 ddiii.
Table 4-21. Non-Cancer Risk Estimates for Acute Inhalation Exposures Following
Occupational Use of 1-BP in Dry Cleaning Based on Modeling (4th Generation Machine)
Health Effect, Endpoint and
Study
Exposure
Level
Acute MOE
Benchmark
MOE
Spot
Cleaner
Machine & Finish
ONU
Developmental Effects
Decreased live litter size (Fi)
(WIL Research. 2001)
Central
tendency
8
8
15
100
High-end
4
3
5
Developmental Effects
Post-Implantation Loss (F0)
(WIL Research. 2001); NLoeistic
Model
Central
tendency
5
5
9
100
High-end
2
2
3
Study: (WIL Research. 2001). Note: Based on acute HEC of 10 ppm and 5.7 ppm.
Table 4-22. Non-Cancer Risk Estimates for Acute Inhalation Exposures Following
Occupational Use of 1-BP in Spot Cleaner Based on Monitoring Data
Health Effect, Endpoint and
Study
Acute
HEC
(ppm)
Exposure Level
Acute MOE
Benchmark
MOE
Worker
ONU
Developmental Effects
Decreased live litter size (Fi)
(WIL Research. 2001)
31
Central tendency
34
No data
100
High-end
7
No data
Developmental Effects
Post-Implantation Loss (F0)
(WIL Research. 2001); NLoeistic
Model
17
Central tendency
19
No data
100
High-end
4
No data
Page 252 of 486
-------
Note: EPA did not identify exposure monitoring data for ONUs. EPA estimated exposure level for ONU through
modeling.
Table 4-23. Non-Cancer Risk Estimates for Acute Inhalation Exposures Following
Occupational Use of 1-BP in Spot Cleaner Based on Modeling
Health Effect, Endpoint and
Study
Acute
HEC
(ppm)
Exposure Level
Acute MOE
Benchmark
MOE
Worker
ONU
Developmental Effects
Decreased live litter size (Fi)
(WIL Research. 2001)
31
Central tendency
10
19
100
High-end
4
7
Developmental Effects
Post-Implantation Loss (F0)
(WIL Research. 2001); NLoeistic
Model
17
Central tendency
5
10
100
High-end
2
4
Table 4-24. Non-Cancer Risk Estimates for Acute Inhalation Exposures Following
Occupational Use of 1-BP in Adhesive Chemicals (Spray Adhesive3) Based on Monitoring
Data (Pre-EC)
Health Effect, Endpoint
and Study
Exposure
Level
Acute MOE
APF=50
Benchmark
MOE
Sprayer
Non-
Sprayer
ONU
Sprayer
Non-
Sprayer
Developmental Effects
Decreased live litter size (Fi)
(WIL Research. 2001)
Central
tendency
0.23
0.24
10
12
12
100
High-end
0.12
0.15
0.24
6
7
Developmental Effects
Post-Implantation Loss (F0)
(WIL Research. 2001):
NLogistic Model
Central
tendency
0.13
0.13
6
6
7
100
High-end
0.07
0.08
0.13
3
4
Note: Based on acute HEC of 31 ppm and 17 ppm.
a EC = Engineering Controls. Pre-EC = Initial NIOSH visit; Post EC = Follow-up NIOSH visit engineering controls
implemented: Enclosing spray tables to create "spray booths" and/or improve ventilation.
Page 253 of 486
-------
Table 4-25. Non-Cancer Risk Estimates for Acute Inhalation Exposures Following
Occupational Use of 1-BP in Adhesive Chemicals (Spray Adhesive) Based on Monitoring
Data (Post-ECa)
Health Effect, Endpoint
and Study
Exposure
Level
Acute MOE
APF=50
Benchmark
MOE
Sprayer
Non-
Sprayer
ONU
Sprayer
Non-
Sprayer
Developmental Effects
Decreased live litter size (Fi)
(WIL Research. 2001)
Central
tendency
2
2
16
87
86
100
High-end
1
1
6
37
54
Developmental Effects
Post-Implantation Loss (F0)
(WIL Research. 2001):
NLogistic Model
Central
tendency
1
1
9
48
47
100
High-end
0.41
1
3
20
29
Note: Based on acute HEC of 31 ppm and 17 ppm.
aEC = Engineering Controls. Pre-EC = Initial NIOSH visit; Post EC = Follow-up NIOSH visit engineering controls
implemented: Enclosing spray tables to create "spray booths" and/or improve ventilation.
Table 4-26. Non-Cancer Risk Estimates for Acute Inhalation Exposures Following
Occupational Use of 1-BP in Disposal Based on Modeling
Health Effect, Endpoint and
Study
Acute
HEC
(ppm)
Exposure Level
Acute MOE
Benchmark
MOE
Worker
ONU
Developmental Effects
Decreased live litter size (Fi)
(WIL Research. 2001)
31
Central tendency
8,099
N/A
100
High-end
546
N/A
Developmental Effects
Post-Implantation Loss (F0)
(WIL Research. 2001):
NLogistic Model
17
Central tendency
4,441
N/A
100
High-end
300
N/A
N/A - not applicable. Because the model assumes tank truck and railcar loading/unloading occurs outdoors, EPA
expects ONU exposure to be negligible due to airborne concentration dilution in ambient air.
4.2.3.2 Acute Consumer Exposures
MOE estimates for acute non-cancer consumer inhalation exposure were determined for nine
consumer conditions of use based on modeling (high, moderate, and low intensity use scenarios)
and are included in the l-BP_Supplemental FileConsumer Exposure Risk Calculations (EPA.
2019c). These MOE estimates are presented in Table 4-27. MOE estimates that are lower than the
Benchmark MOE (Total UF) are highlighted in red.
Page 254 of 486
-------
Table 4-27. Non-Cancer Risk Estimates for Acute 24-hr Inhalation Exposure Following
Consumer Uses of 1-BP (Benchmark MOE = 100) Based on Modeling
Acute Non-Cancer MOE (24-Hour TWA)
Developmental Effects
Developmental Effects
Condition of Use
Scenario Description
Decreased live litter size (Fi)
(WIL Research. 2001)
Post-Implantation Loss (F0)
(WIL Research. 2001)
User
Bystander
User
Bystander
Aerosol spray
High Intensity Use
7.1E-02
0.24
4.3E-02
0.15
degreaser/cleaner-
Moderate Intensity Use
0.53
2.0
0.316
1.2
general
Low Intensity Use
10
40
6.0
24
Aerosol spray
High Intensity Use
0.33
1.2
0.20
0.69
degreaser/cleaner-
Moderate Intensity Use
7.1
29
4.3
17
electronics
Low Intensity Use
149
526
90
316
Spot cleaner and
stain remover
High Intensity Use
0.21
1.4
0.13
0.83
Moderate Intensity Use
2.9
19
1.8
11
Low Intensity Use
38
208
23
125
Coin and scissors
cleaner
High Intensity Use
5.0
10
3.0
6.0
Moderate Intensity Use
6.7
21
4.0
13
Low Intensity Use
8.3
45
5.0
27
Spray cleaner-
general
High Intensity Use
7.5E-02
0.30
4.5E-02
0.18
Moderate Intensity Use
0.71
3.7
0.43
2.2
Low Intensity Use
4.3
23
2.6
14
Adhesive
accelerant
High Intensity Use
0.56
2.2
0.33
1.3
Moderate Intensity Use
9.1
50
5.5
30
Low Intensity Use
83
400
50
240
Automobile AC
flush
High Intensity Use
13
20
7.5
12
Moderate Intensity Use
19
42
11
25
Low Intensity Use
27
133
16
80
Mold cleaning and
release product
High Intensity Use
0.48
2.4
0.29
1.4
Moderate Intensity Use
7.1
37
4.3
22
Low Intensity Use
83
385
50
231
Insulation (off-
Attic
N/A
5,050
N/A
3,030
gassing)
Living Space
N/A
11,104
N/A
6,663
[A/LS/C]*
Crawlspace
N/A
4,666
N/A
2,800
Insulation (off-
Attic
N/A
5,128
N/A
3,077
gassing)
Living Space
N/A
31,439
N/A
18,863
[A/LS/B]*
Full Basement
N/A
4,782
N/A
2,869
Note: Acute HEC = 6 ppm (decreased live litter size) and 10 ppm (post-implantation loss).
N/A - Not applicable because EPA assumes consumer exposure from off-gassing will occur after installation.
Page 255 of 486
-------
* Insulation (off-gassing) was evaluated for two building configurations. Attic/Living Space/Crawlspace [A/LS/C] and
Attic/Living Space/Basement [A/LS/B]
MOE estimates were generally below the benchmark MOE of 100 by 1-2 orders of magnitude for
both the user and bystander for all consumer conditions of use evaluated except for the insulation
(off-gassing) condition of use and some low intensity use scenarios for the bystander.
4,2,4 Risk Characterization for Chronic Exposure Scenarios
4.2.4.1 Non-Cancer MOEs for Chronic, Non-Cancer Occupational Inhalation
Exposures and Consumer Insulation (Off-Gassing) Condition of Use
EPA estimated the non-cancer MOEs associated with chronic exposures following 1-BP conditions
of use in the workplace as well as the insulation (off-gassing) condition of use for the consumer
bystander. Since 1-BP exposure may be associated with a variety of non-cancer health effects, this
assessment estimated MOEs for liver toxicity, kidney toxicity, reproductive toxicity,
developmental toxicity and neurotoxicity following chronic inhalation exposures. EPA used the
HEC specific to each health effect domain for calculating MOE estimates. MOE estimates that are
lower than the Benchmark MOE are highlighted in red.
Table 4-28 through Table 4-47 present the non-cancer risks for chronic occupational scenarios.
MOE estimates for a range of health effects were calculated (See the Supplemental File:
Occupational Risk Calculator (EPA1_2019g)). Where the sample size of the underlying exposure
data is sufficiently large to calculate statistics, the central tendency estimate is based on the 50th
percentile exposure level of the dataset, while the high-end estimate is based on the 95th percentile
exposure. See Section 2.3.1.2 for detailed descriptions of central tendency and high-end estimates.
These tables also evaluate the impact of potential respirator use and present the respirator that would
be needed (based on respirator APF of 10, 25, and 50) to mitigate risk for all health domain. The
MOE estimates for these respirator scenarios assume workers wear respirators for the entire
duration of the work activity throughout their career (e.g., typically 260 days per year and over 31
years per lifetime for many occupational scenarios). Because respirators are uncomfortable,
interfere with communication, limit vision, and make it hard to breathe, and the onus is on the
worker to don and doff them correctly, the use of respirators on a continuous, long-term basis may
not be practical. As explained in Section 4.2.2, APFs were not applied to the dry cleaning, spot
cleaning, and aerosol degreasing scenarios because EPA assumes respirator use is unlikely for
these conditions of use. In addition, EPA does not evaluate respirator use for occupational non-
users because they do not directly handle 1-BP and are unlikely to wear respirators. For chronic
occupational exposure scenarios, EPA did not assess risks to children who may be present in the
workplace (e.g., dry cleaners) because their presence in the workplace is likely intermittent and
overall exposure is not expected to be chronic in nature.
Page 256 of 486
-------
Table 4-28. Non-Cancer Risk Estimates for Chronic Inhalation Exposures Following
Occupational Use of 1-BP in Manufacture (U.S.) Based on Monitoring Data
Health Effect, Endpoint
and Study
Chronic
HEC
(ppm)
Exposure
Level
Chronic MOE
APF=10
Benchmark
MOE
Worker
ONU
Worker
Liver
Increased hepatocellular
vacuolization
(WIL Research. 2001)
150
Central
tendency
1,667
N/A
16,667
100
High-end
556
N/A
5,556
Kidney
Increased pelvic
mineralization
(WIL Research. 2001)
180
Central
tendency
2,000
N/A
20,000
100
High-end
667
N/A
6,667
Reproductive System
Decreased seminal vesicle
weight
(Ichihara et al.. 2000b)
53
Central
tendency
589
N/A
5,889
100
High-end
196
N/A
1,963
Developmental Effects
Decreased live litter size (Fi)
(WIL Research. 2001)
31
Central
tendency
484
N/A
4,835
100
High-end
161
N/A
1,612
Developmental Effects
Post-Implantation Loss (F0)
(WIL Research. 2001):
NLogistic Model
17
Central
tendency
265
N/A
2,652
100
High-end
88
N/A
884
Nervous System
Decreased traction time
(Honma et al.. 2003)
25
Central
tendency
278
N/A
2,778
100
High-end
93
N/A
926
Notes: 1 MOEs (HEC in ppm/exposure estimate in ppm) lower than the Benchmark MOE (Total UF) indicate potential
health risks and are denoted in bold. Exposure monitoring was not performed for ONUs at this manufacturing facility.
Based on the process and work activity description, exposure to ONU is expected to be negligible.
Page 257 of 486
-------
Table 4-29. Non-Cancer Risk Estimates for Chronic Inhalation Exposures Following
Occupational Use of 1-BP in Import, Processing as a Reactant, and Processing -
Incorporation into Articles Based on Modeling
Health Effect, Endpoint and
Study
Chronic
HEC
(ppm)
Exposure
Level
Chronic MOE
Benchmark
MOE
Worker
ONU
Liver
Increased hepatocellular
vacuolization
(WIL Research. 2001)
150
Central
tendency
39,188
N/A
100
High-end
2,644
N/A
Kidney
Increased pelvic mineralization
(WIL Research. 2001)
180
Central
tendency
47,026
N/A
100
High-end
3,173
N/A
Reproductive System
Decreased seminal vesicle
weight
(Ichihara et al.. 2000b)
53
Central
tendency
13,846
N/A
100
High-end
934
N/A
Developmental Effects
Decreased live litter size (Fi)
(WIL Research. 2001)
31
Central
tendency
11,370
N/A
100
High-end
767
N/A
Developmental Effects
Post-Implantation Loss (F0)
(WIL Research. 2001):
NLogistic Model
17
Central
tendency
6,235
N/A
100
High-end
421
N/A
Nervous System
Decreased traction time
(Honma et al.. 2003)
25
Central
tendency
6,531
N/A
100
High-end
441
N/A
N/A - Not applicable. Because the model assumes tank track and railcar loading/unloading occurs outdoors, EPA
expects ONU exposure to be negligible due to airborne concentration dilution in ambient air.
Table 4-30. Non-Cancer Risk Estimates for Chronic Inhalation Exposures Following
Occupational Use of 1-BP in Processing - Incorporation into Formulation Based on
Monitoring Data
Health Effect, Endpoint and
Study
Chronic
HEC
(ppm)
Exposure
Level
Chronic MOE
APF=50
Benchmark
MOE
Worker
ONU
Worker
Liver
Increased hepatocellular
vacuolization
(WIL Research. 2001)
150
Central
tendency
21
968
1,042
100
High-end
544
Page 258 of 486
-------
Health Effect, Endpoint and
Study
Chronic
HEC
(ppm)
Exposure
Level
Chronic MOE
APF=50
Benchmark
MOE
Worker
ONU
Worker
Kidney
Increased pelvic mineralization
(WIL Research. 2001)
180
Central
tendency
25
1,161
1,250
100
High-end
653
Reproductive System
Decreased seminal vesicle
weight
(Ichihara et al.. 2000b)
53
Central
tendency
7
342
368
100
High-end
192
Developmental Effects
Decreased live litter size (Fi)
(WIL Research. 2001)
31
Central
tendency
6
281
302
100
High-end
158
Developmental Effects
Post-Implantation Loss (F0)
(WIL Research. 2001):
NLogistic Model
17
Central
tendency
3
154
166
100
High-end
87
Nervous System
Decreased traction time
(Honma et al.. 2003)
25
Central
tendency
3
161
174
100
High-end
91
Table 4-31. Non-Cancer Risk Estimates for Chronic Inhalation Exposures Following
Occupational Use of 1-BP in Batch Vapor Degreaser (Open-Top) Based on Monitoring Data
Health Effect, Endpoint
and Study
Chronic
HEC
(ppm)
Exposure
Level
Chronic MOE
APF=50
Benchmark
MOE
Worker
ONU
Worker
Liver
Increased hepatocellular
vacuolization
(WIL Research. 2001)
150
Central
tendency
22
1,500
1,119
100
High-end
3
326
152
Kidney
Increased pelvic
mineralization
(WIL Research. 2001)
180
Central
tendency
27
1,800
1,343
100
High-end
4
391
183
Reproductive System
Decreased seminal vesicle
weight
(Ichihara et al.. 2000b)
53
Central
tendency
8
530
396
100
High-end
1
115
54
Developmental Effects
Decreased live litter size (Fi)
(WIL Research. 2001)
31
Central
tendency
6
435
325
100
High-end
1
95
44
Page 259 of 486
-------
Health Effect, Endpoint
and Study
Chronic
Exposure
Level
Chronic MOE
APF=50
Benchmark
MOE
HEC
(ppm)
Worker
ONU
Worker
Developmental Effects
Post-Implantation Loss (F0)
17
Central
tendency
4
239
178
100
(WIL Research. 2001):
NLogistic Model
High-end
0.48
52
24
Nervous System
Decreased traction time
(Honma et al.. 2003)
25
Central
tendency
4
250
187
100
High-end
0.51
54
25
Table 4-32. Non-Cancer Risk Estimates for Chronic Inhalation Exposures Following
Occupational Use of 1-BP in Batch Vapor Degreaser (Open-Top) (Pre-EC) Based on
Modeling
Health Effect, Endpoint
and Study
Chronic
Exposure
Level
Chronic MOE
APF=50
Benchmark
MOE
HEC
(ppm)
Worker
ONU
Worker
Liver
Increased hepatocellular
150
Central
tendency
79
151
3,967
100
vacuolization
(WIL Research. 2001)
High-end
6
11
314
Kidney
Increased pelvic
180
Central
tendency
95
181
4,760
100
mineralization
(WIL Research. 2001)
High-end
8
13
376
Reproductive System
Decreased seminal vesicle
53
Central
tendency
28
53
1,402
100
weight
(Ichihara et al.. 2000b)
High-end
2
4
111
Developmental Effects
Decreased live litter size (Fi)
(WIL Research. 2001)
31
Central
tendency
23
44
1,151
100
High-end
2
3
91
Developmental Effects
Post-Implantation Loss (F0)
17
Central
tendency
13
24
631
100
(WIL Research. 2001):
NLogistic Model
High-end
1
2
50
Nervous System
Decreased traction time
(Honma et al.. 2003)
25
Central
tendency
13
25
661
100
High-end
1
2
52
Page 260 of 486
-------
Table 4-33. Non-Cancer Risk Estimates for Chronic Inhalation Exposures Following
Occupational Use of 1-BP in Batch Vapor Degreaser (Open-Top) (Post-EC) Based on
Modeling
Health Effect, Endpoint and
Study
Chronic
HEC
(ppm)
Exposure
Level
Chronic MOE
APF=25
Benchmark
MOE
Worker
ONU
Worker
Liver
Increased hepatocellular
vacuolization
(WIL Research. 2001)
150
Central
tendency
793
1,510
19,835
100
High-end
63
111
1,568
Kidney
Increased pelvic
mineralization
(WIL Research. 2001)
180
Central
tendency
952
1,812
23,802
100
High-end
75
133
1,881
Reproductive System
Decreased seminal vesicle
weight
(Ichihara et al.. 2000b)
53
Central
tendency
280
534
7,009
100
High-end
22
39
554
Developmental Effects
Decreased live litter size (Fi)
(WIL Research. 2001)
31
Central
tendency
230
438
5,755
100
High-end
18
32
455
Developmental Effects
Post-Implantation Loss (F0)
(WIL Research. 2001):
NLogistic Model
17
Central
tendency
126
240
3,156
100
High-end
10
18
249
Nervous System
Decreased traction time
(Honma et al.. 2003)
25
Central
tendency
132
252
3,306
100
High-end
10
19
261
Table 4-34. Non-Cancer Risk Estimates for Chronic Inhalation Exposures Following
Occupational Use of 1-BP in Batch Vapor Degreaser (Closed-Loop) Based on Modeling
Health Effect, Endpoint
and Study
Chronic
HEC
(ppm)
Chronic MOE
APF=10
Benchmark
MOE
Level
Worker
ONU
Worker
Liver
Increased hepatocellular
vacuolization
(WIL Research. 2001)
1 SO
Central
tendency
3,967
7,551
39,671
100
I jU
High-end
314
555
3,135
Kidney
Increased pelvic
180
Central
tendency
4,760
9,062
47,605
100
Page 261 of 486
-------
mineralization
(WIL Research. 2001)
High-end
376
666
3,763
Reproductive System
Decreased seminal vesicle
weight
(Ichihara et al.. 2000b)
53
Central
tendency
1,402
2,668
14,017
100
High-end
111
196
1,108
Developmental Effects
Decreased live litter size (Fi)
(WIL Research. 2001)
31
Central
tendency
1,151
2,191
11,510
100
High-end
91
161
910
Developmental Effects
Post-Implantation Loss (F0)
(WIL Research. 2001):
NLogistic Model
17
Central
tendency
631
1,201
6,312
100
High-end
50
88
499
Nervous System
Decreased traction time
(Honma et al.. 2003)
25
Central
tendency
661
1,259
6,612
100
High-end
52
93
523
Table 4-35. Non-Cancer Risk Estimates for Chronic Inhalation Exposures Following
Occupational Use of 1-BP in Cold Cleaner Based on Monitoring Data
Health Effect, Endpoint
and Study
Chronic
HEC
(ppm)
Exposure
Level
Chronic MOE
APF=50
Benchmark
MOE
Worker
ONU
Worker
Liver
Increased hepatocellular
vacuolization
(WIL Research. 2001)
150
Central
tendency
35
58
1,744
100
High-end
20
58
1,014
Kidney
Increased pelvic
mineralization
(WIL Research. 2001)
180
Central
tendency
42
69
2,093
100
High-end
24
69
1,216
Reproductive System
Decreased seminal vesicle
weight
(Ichihara et al.. 2000b)
53
Central
tendency
12
20
616
100
High-end
7
20
358
Developmental Effects
Decreased live litter size (Fi)
(WIL Research. 2001)
31
Central
tendency
10
17
506
100
High-end
6
17
294
Developmental Effects
Post-Implantation Loss (F0)
(WIL Research. 2001):
NLogistic Model
17
Central
tendency
6
9
278
100
High-end
3
9
161
Page 262 of 486
-------
Nervous System
Decreased traction time
(Honma et al.. 2003)
25
Central
tendency
6
10
291
100
High-end
3
10
169
Table 4-36. Non-Cancer Risk Estimates for Chronic Inhalation Exposures Following
Occupational Use of 1-BP in Cold Cleaner Based on Modeling
Health Effect, Endpoint
and Study
Chronic
HEC
(ppm)
Exposure
Level
Chronic MOE
APF=50
Benchmark
MOE
Worker
ONU
Worker
Liver
Increased hepatocellular
vacuolization
(WIL Research. 2001)
150
Central
tendency
273
519
13,657
100
High-end
13
22
630
Kidney
Increased pelvic
mineralization
(WIL Research. 2001)
180
Central
tendency
328
623
16,388
100
High-end
15
26
756
Reproductive System
Decreased seminal vesicle
weight
(Ichihara et al.. 2000b)
53
Central
tendency
97
183
4,825
100
High-end
4
8
223
Developmental Effects
Decreased live litter size (Fi)
(WIL Research. 2001)
31
Central
tendency
79
151
3,962
100
High-end
4
6
183
Developmental Effects
Post-Implantation Loss (F0)
(WIL Research. 2001):
NLogistic Model
17
Central
tendency
43
83
2,173
100
High-end
2
3
100
Nervous System
Decreased traction time
(Honma et al.. 2003)
25
Central
tendency
46
86
2,276
100
High-end
2
4
105
Table 4-37. Non-Cancer Risk Estimates for Chronic Inhalation Exposures Following
Occupational Use of 1-BP in Aerosol Spray Degreaser/Cleaner (Pre-ECa) Based on
Monitoring Data
Health Effect, Endpoint
and Study
Chronic
HEC
(ppm)
Exposure
Level
Chronic MOE
Benchmark
MOE
Worker
ONU
Liver
Increased hepatocellular
150
Central
tendency
9
No data
100
Page 263 of 486
-------
Health Effect, Endpoint
and Study
Chronic
HEC
(ppm)
Exposure
Level
Chronic MOE
Benchmark
MOE
Worker
ONU
vacuolization
(WIL Research. 2001)
High-end
5
No data
Kidney
Increased pelvic
mineralization
(WIL Research. 2001)
180
Central
tendency
11
No data
100
High-end
6
No data
Reproductive System
Decreased seminal vesicle
weight
(Ichihara et al.. 2000b)
53
Central
tendency
3
No data
100
High-end
2
No data
Developmental Effects
Decreased live litter size (Fi)
(WIL Research. 2001)
31
Central
tendency
3
No data
100
High-end
1
No data
Developmental Effects
Post-Implantation Loss (F0)
(WIL Research. 2001):
NLogistic Model
17
Central
tendency
1
No data
100
High-end
1
No data
Nervous System
Decreased traction time
(Honma et al.. 2003)
25
Central
tendency
2
No data
100
High-end
1
No data
Note: EPA did not identify exposure monitoring data for ONUs. EPA estimated exposure level for ONU through
modeling.a EC = Engineering Controls.
Page 264 of 486
-------
Table 4-38. Non-Cancer Risk Estimates for Chronic Inhalation Exposures Following
Occupational Use of 1-BP in Aerosol Spray Degreaser/Cleaner (Post-ECa) Based on
Monitoring Data
Health Effect, Endpoint
and Study
Chronic
HEC
(ppm)
Exposure
Level
Chronic MOE
Benchmark
MOE
Worker
ONU
Liver
Increased hepatocellular
vacuolization
(WIL Research. 2001)
150
N/A
(single
data
point)
27
No data
100
No data
Kidney
Increased pelvic
mineralization
(WIL Research. 2001)
180
33
No data
100
No data
Reproductive System
Decreased seminal vesicle
weight
(Ichihara et al.. 2000b)
53
10
No data
100
No data
Developmental Effects
Decreased live litter size (Fi)
(WIL Research. 2001)
31
8
No data
100
No data
Developmental Effects
Post-Implantation Loss (F0)
(WIL Research. 2001):
NLogistic Model
17
4
No data
100
No data
Nervous System
Decreased traction time
(Honma et al.. 2003)
25
5
No data
100
No data
Note: EPA did not identify exposure monitoring data for ONUs. EPA estimated exposure level for ONU through
modeling.
aEC = Engineering Controls. Post-EC = The vented booth scenario from Tech Spray study.
Page 265 of 486
-------
Table 4-39. Non-Cancer Risk Estimates for Chronic Inhalation Exposures Following
Occupational Use of 1-BP in Aerosol Spray Degreaser/Cleaner Based on Modeling
Health Effect, Endpoint and
Study
Chronic
HEC
(ppm)
Exposure
Level
Chronic MOE
Benchmark
MOE
Worker
ONU
Liver
Increased hepatocellular
vacuolization
(WIL Research. 2001)
150
Central
tendency
24
1,364
100
High-end
7
161
Kidney
Increased pelvic
mineralization
(WIL Research. 2001)
180
Central
tendency
28
1,636
100
High-end
8
194
Reproductive System
Decreased seminal vesicle
weight
(Ichihara et al.. 2000b)
53
Central
tendency
8
482
100
High-end
2
57
Developmental Effects
Decreased live litter size (Fi)
(WIL Research. 2001)
31
Central
tendency
7
396
100
High-end
2
47
Developmental Effects
Post-Implantation Loss (F0)
(WIL Research. 2001):
NLogistic Model
17
Central
tendency
4
217
100
High-end
1
26
Nervous System
Decreased traction time
(Honma et al.. 2003)
25
Central
tendency
4
227
100
High-end
1
27
Page 266 of 486
-------
Table 4-40. Non-Cancer Risk Estimates for Chronic Inhalation Exposures Following
Occupational Use of 1-BP in Adhesive Chemicals (Spray Adhesives) (Pre-ECa) Based on
Monitoring Data
Health Effect, Endpoint
and Study
Exposure
Level
Chronic MOE
APF=50
Benchmark
MOE
Sprayer
Non-
Sprayer
ONU
Sprayer
Non-
Sprayer
Liver
Increased hepatocellular
vacuolization
(WIL Research. 2001)
Central
tendency
1
1
50
56
59
100
High-end
0.59
0.71
1.2
30
36
Kidney
Increased pelvic
mineralization
(WIL Research. 2001)
Central
tendency
1
1
60
68
71
100
High-end
0.71
0.85
1
35
43
Reproductive System
Decreased seminal vesicle
weight
(Ichihara et al.. 2000b)
Central
tendency
0.40
0.42
18
20
21
100
High-end
0.21
0.25
0.41
10
13
Developmental Effects
Decreased live litter size (Fi)
(WIL Research. 2001)
Central
tendency
0.3
0.34
14.5
16
17
100
High-end
0.2
0.21
0.34
9
10
Developmental Effects
Post-Implantation Loss
(WIL Research. 2001):
NLogistic Model
Central
tendency
0.3
0.26
11.2
13
13
100
High-end
0.13
0.16
0.26
7
8
Nervous System
Decreased traction time
(Honma et al.. 2003)
Central
tendency
0.19
0.20
8
9
10
100
High-end
0.099
0.12
0.19
5
6
Note: Based on HEC values of 150 ppm, 140 ppm, 53 ppm, 43 ppm, 24 ppm, and 25 ppm.
aEC = Engineering Controls. Pre-EC = Initial NIOSH visit; Post EC = Follow-up NIOSH visit engineering controls
implemented: Enclosing spray tables to create "spray booths" and/or improve ventilation.
Table 4-41. Non-Cancer Risk Estimates for Chronic Inhalation Exposures Following
Occupational Use of 1-BP in Adhesive Chemicals (Spray Adhesives) (Post-ECa) Based on
Monitoring Data
Health Effect, Endpoint
and Study
Exposure
Level
Chronic MOE
APF=50
Benchmark
MOE
Sprayer
Non-
Sprayer
ONU
Sprayer
Non-
Sprayer
Liver
Increased hepatocellular
vacuolization
(WIL Research. 2001)
Central
tendency
8
8
75
421
417
100
High-end
4
5
27
179
260
Kidney
Increased pelvic
mineralization
(WIL Research. 2001)
Central
tendency
10
10
90
505
500
100
High-end
4
6
33
215
312
Page 267 of 486
-------
Health Effect, Endpoint
and Study
Exposure
Level
Chronic MOE
APF=50
Benchmark
MOE
Sprayer
Non-
Sprayer
ONU
Sprayer
Non-
Sprayer
Reproductive System
Decreased seminal vesicle
weight
(Ichihara et al.. 2000b)
Central
tendency
3
3
27
149
147
100
High-end
1
2
10
63
92
Developmental Effects
Decreased live litter size
(Fi)
(WIL Research. 2001)
Central
tendency
2
2
22
122
121
100
High-end
1
2
8
52
75
Developmental Effects
Post-Implantation Loss
(WIL Research. 2001):
NLogistic Model
Central
tendency
2
2
17
95
94
100
High-end
1
1
6
40
58
Nervous System
Decreased traction time
(Honma et al.. 2003)
Central
tendency
1
1
13
70
69
100
High-end
1
1
5
30
43
Note: Based on HEC values of 150 ppm, 140 ppm, 53 ppm, 43 ppm, 24 ppm, and 25 ppm.
aEC = Engineering Controls. Pre-EC = Initial NIOSH visit; Post EC = Follow-up NIOSH visit engineering controls
implemented: Enclosing spray tables to create "spray booths" and/or improve ventilation.
Table 4-42. Non-Cancer Risk Estimates for Chronic Inhalation Exposures Following
Occupational Use of 1-BP in Dry Cleaning Based on Monitoring Data
Health Effect, Endpoint and
Study
Chronic
HEC (ppm)
Exposure
Level
Chronic MOE
Benchmark
MOE
Worker
ONU
Liver
Increased hepatocellular
vacuolization
(WIL Research. 2001)
150
Central
tendency
5
12
100
High-end
3
7
Kidney
Increased pelvic
mineralization
(WIL Research. 2001)
180
Central
tendency
6
15
100
High-end
4
9
Reproductive System
Decreased seminal vesicle
weight
(Ichihara et al.. 2000b)
53
Central
tendency
2
4
100
High-end
1
3
Developmental Effects
Decreased live litter size (Fi)
(WIL Research. 2001)
31
Central
tendency
1
4
100
High-end
1
2
Developmental Effects
Post-Implantation Loss (F0)
17
Central
tendency
1
2
100
Page 268 of 486
-------
Health Effect, Endpoint and
Study
Chronic
HEC (ppm)
Exposure
Level
Chronic MOE
Benchmark
MOE
Worker
ONU
(WIL Research. 2001):
NLogistic Model
High-end
0.42
1
Nervous System
Decreased traction time
(Honma et al.. 2003)
25
Central
tendency
0.85
2
100
High-end
0.50
1
Table 4-43. Non-Cancer Risk Estimates for Chronic Inhalation Exposures Following
Occupational Use of 1-BP in Dry Cleaning Based on Modeling (3rd Generation)
Health Effect, Endpoint and
Study
Exposure
Level
Chronic MOE
Benchmark
MOE
Spot
Cleaner
Machine
& Finish
ONU
Liver
Increased hepatocellular
vacuolization
(WIL Research. 2001)
Central
tendency
35
7
56
100
High-end
13
2
15
Kidney
Increased pelvic mineralization
(WIL Research. 2001)
Central
tendency
43
9
69
100
High-end
16
2
19
Reproductive System
Decreased seminal vesicle weight
(Ichihara et al.. 2000b)
Central
tendency
13
3
20
100
High-end
5
1
5
Developmental Effects
Decreased live litter size (Fi)
(WIL Research. 2001)
Central
tendency
10
2
16
100
High-end
4
0.46
4
Developmental Effects
Post-Implantation Loss
(WIL Research. 2001); NLoeistic
Model
Central
tendency
5
1
9
100
High-end
2
0.26
2
Nervous System
Decreased traction time
(Honma et al.. 2003)
Central
tendency
6
1
10
100
High-end
2
0.28
3
Table 4-44. Non-Cancer Risk Estimates for Chronic Inhalation Exposures Following
Occupational Use of 1-BP in Dry Cleaning Based on Modeling (4th Generation)
Health Effect, Endpoint and
Study
Exposure
Level
Chronic MOE
Benchmark
MOE
Spot
Cleaner
Machine
& Finish
ONU
Liver
Increased hepatocellular
Central
tendency
42
43
78
100
High-end
18
16
24
Page 269 of 486
-------
vacuolization
(WIL Research. 2001)
Kidney
Increased pelvic mineralization
(WIL Research. 2001)
Central
tendency
52
53
96
100
High-end
22
19
30
Reproductive System
Decreased seminal vesicle weight
(Ichihara et al.. 2000b)
Central
tendency
15
16
28
100
High-end
6
6
9
Developmental Effects
Decreased live litter size (Fi)
(WIL Research. 2001)
Central
tendency
12
12
22
100
High-end
5
4.4
7
Developmental Effects
Post-Implantation Loss
(WIL Research. 2001); NLoeistic
Model
Central
tendency
7
7
12
100
High-end
3
3
4
Nervous System
Decreased traction time
(Honma et al.. 2003)
Central
tendency
7
7
13
100
High-end
3
3
4
Table 4-45. Non-Cancer Risk Estimates for Chronic Inhalation Exposures Following
Occupational Use of 1-BP in Spot Cleaner Based on Monitoring Data
Health Effect, Endpoint and
Study
Chronic
HEC
(ppm)
Exposure
Level
Chronic MOE
Benchmark
MOE
Worker
ONU
Liver
Increased hepatocellular
vacuolization
(WIL Research. 2001)
150
Central
tendency
167
No data
100
High-end
32
No data
Kidney
Increased pelvic mineralization
(WIL Research. 2001)
180
Central
tendency
200
No data
100
High-end
38
No data
Reproductive System
Decreased seminal vesicle weight
(Ichihara et al.. 2000b)
53
Central
tendency
59
No data
100
High-end
11
No data
Developmental Effects
Decreased live litter size (Fi)
(WIL Research. 2001)
31
Central
tendency
48
No data
100
High-end
9
No data
Developmental Effects
Post-Implantation Loss (F0)
(WIL Research. 2001); NLoeistic
Model
17
Central
tendency
27
No data
100
High-end
5
No data
25
Central
tendency
28
No data
100
Page 270 of 486
-------
Health Effect, Endpoint and
Study
Chronic
HEC
(ppm)
Exposure
Level
Chronic MOE
Benchmark
MOE
Worker
ONU
Nervous System
Decreased traction time
(Honma et al.. 2003)
High-end
5
No data
Note: EPA did not identify exposure monitoring data for ONUs. EPA estimated exposure level for ONU through
modeling.
Table 4-46. Non-Cancer Risk Estimates for Chronic Inhalation Exposures Following
Occupational Use of 1-BP in Spot Cleaner Based on Modeling
Health Effect, Endpoint and
Study
Chronic
HEC
(ppm)
Exposure
Level
Chronic MOE
Benchmark
MOE
Worker
ONU
Liver
Increased hepatocellular
vacuolization
(WIL Research. 2001)
150
Central
tendency
197
390
100
High-end
90
136
Kidney
Increased pelvic mineralization
(WIL Research. 2001)
180
Central
tendency
236
468
100
High-end
108
163
Reproductive System
Decreased seminal vesicle weight
(Ichihara et al.. 2000b)
53
Central
tendency
70
138
100
High-end
32
48
Developmental Effects
Decreased live litter size (Fi)
(WIL Research. 2001)
31
Central
tendency
57
113
100
High-end
26
39
Developmental Effects
Post-Implantation Loss (F0)
(WIL Research. 2001); NLoeistic
Model
17
Central
tendency
31
62
100
High-end
14
22
Nervous System
Decreased traction time
(Homna et al.. 2003)
25
Central
tendency
33
65
100
High-end
15
23
Page 271 of 486
-------
Table 4-47. Non-Cancer Risk Estimates for Chronic Inhalation Exposures Following
Occupational Use of 1-BP in Disposal Based on Modeling
Health Effect, Endpoint and
Study
Chronic
HEC
(ppm)
Exposure
Level
Chronic MOE
Benchmark
MOE
Worker
ONU
Liver
Increased hepatocellular
vacuolization
(WIL Research. 2001)
150
Central
tendency
39,188
N/A
100
High-end
2,644
N/A
Kidney
Increased pelvic mineralization
(WIL Research. 2001)
180
Central
tendency
47,026
N/A
100
High-end
3,173
N/A
Reproductive System
Decreased seminal vesicle weight
(Ichihara et al.. 2000b)
53
Central
tendency
13,846
N/A
100
High-end
934
N/A
Developmental Effects
Decreased live litter size (Fi)
(WIL Research. 2001)
31
Central
tendency
11,370
N/A
100
High-end
767
N/A
Developmental Effects
Post-Implantation Loss (F0)
(WIL Research. 2001); NLoeistic
Model
17
Central
tendency
6,235
N/A
100
High-end
421
N/A
Nervous System
Decreased traction time
(Honma et al.. 2003)
25
Central
tendency
6,531
N/A
100
High-end
441
N/A
N/A - Not applicable. Because the model assumes tank track and railcar loading/unloading occurs outdoors, EPA
expects ONU exposure to be negligible due to airborne concentration dilution in ambient air.
Consumer MOE Estimates for Non-Cancer Chronic Exposure
MOE estimates for chronic consumer exposures were only derived for the insulation (off-gassing)
condition of use. The remaining conditions of use were not evaluated for chronic consumer
exposures because they were not considered chronic in nature. Table 4-48 provides a summary of
the MOE estimates for non-cancer chronic inhalation exposures under the insulation (off-gassing)
condition of use. The supporting calculations are included in the l-BP_Supplemental
FileConsumer Exposure Risk Calculations (EPA. 2019c)
Table 4-48. Non-Cancer Risk Estimates for Chronic Inhalation Exposures Following
Installation of THERMAX™ Rigid Insulation Board Within a Residence Based on Modeling
Condition of
Use
Scenario
Description
Chronic Non-Cancer MOE (7-Year Average TWA)
Liver
Kidney
Reproductive
Developmental 1
Developmental 2
Insulation
(off-gassing)
[A/LS/C]
Attic
Living Space
Crawlspace
7.4E+05 9.0E+05 2.7E+05 2.0E+05 1.2E+05
1.8E+06 2.3E+06 6.7E+05 5.1E+05 3.1E+05
8.1E+05 9.9E+05 2.9E+05 2.3E+05 1.4E+05
Page 272 of 486
-------
Insulation
Attic
7.5E+05
9.1E+05
2.7E+05
2.1E+05
1.2E+05
(off-gassing)
Living Space
4.6E+06
5.6E+06
1.7E+06
1.3E+06
7.6E+05
[A/LS/B]
Basement
7.8E+05
9.5E+05
2.8E+05
2.2E+05
1.3E+05
MOE estimates were all at least three orders of magnitude above the benchmark MOE of 100 for
non-cancer chronic inhalation exposures.
4.2.4.2 Cancer Evaluation for Occupational Scenarios
EPA estimated the excess cancers associated with chronic inhalation and dermal exposures
following 1-BP conditions of use in the workplace, based on monitoring data and modeling
(probabilistic vs deterministic). The excess cancer estimation for 1-BP consisted of multiplying the
occupational scenario-specific estimates (i.e., LADC) for both workers and occupational non-users
by EPA's inhalation unit risk (IUR) to estimate the excess cancers. Excess cancer risks were
expressed as number of cancer cases per million. For chronic occupational exposure scenarios,
EPA did not assess risks to children who may be present in the workplace (e.g., dry cleaners)
because their presence in the workplace is likely intermittent and overall exposure is not expected
to be chronic in nature.
Table 4-49 presents the inhalation cancer risk estimates for all occupational 1-BP conditions of
use. The table also presents the impact of potential respirator use based on respirator APF of 10,
25, and 50. Figure 4-1 and Figure 4-2 present the incremental individual lifetime cancer risks for
the 50th and 95th percentile for exposures to 1-BP during these same occupational conditions of use.
The exposure frequency (i.e., the amount of days per year for workers or occupational non-users
exposed to 1-BP) was assumed to be 260 days per year for all conditions of use except for dry
cleaning, where employees at small, family-owned businesses were assumed to work up to six days
per week over 52 weeks per year. The number of working years was assumed to be 31 years as
central tendency, and 40 years as high-end over a 78-year lifespan.
EPA, consistent with OSHA (878 F.2d 389 (D.C. Cir. 1989)) and 2016 NIOSH guidance, used
lxlO"4 as the benchmark for determining cancer risk to individuals in industrial and commercial
work environments subject to OSHA requirements. EPA has consistently applied a cancer risk
benchmark of lxlO"4 for assessment of occupational scenarios under TSCA. This is in contrast
with cancer risk assessments for consumers or the general population, for which lxlO"6 is applied
as a benchmark (Section 4.2.4.3). The lxlO"4 value is not a bright line and EPA has discretion to find
unreasonable risk based on other benchmarks as appropriate. Cancer risk estimates that exceed the
benchmark are highlighted in red below.
Page 273 of 486
-------
Table 4-49. Inhalation Cancer Risk Estimates for Occupational Use of 1-BP (Benchmark = lxlO"4)
Condition of Use
Category
IUR
(ppnr1)
Cancer Risk
Respirator
APF
Cancer Risk with
Respirator
Exposure Data
Type
Central
tendency
High-end
Central
tendency
High-end
Manufacturing (US)
-
Worker
0.004
1.4E-04
5.5E-04
10
1.4E-05
5.5E-05
Monitoring Data
Import, Repackaging, Processing ~
Incorporation into Article
-
Worker
0.004
6.1E-06
1.2E-04
10
6.1E-07
1.2E-05
Model
(Deterministic)
Processing - Incorporation into
Formulation
-
Worker
0.004
1.1E-02
50
2.3E-04
Monitoring Data
-
ONU
0.004
2.5E-04
5.7E-04
N/A
N/A
N/A
Vapor Degreasing, Open-Top
-
Worker
0.004
1.1E-02
1.0E-01
50
2.1E-04
2.0E-03
Monitoring Data
-
ONU
0.004
1.6E-04
9.4E-04
N/A
N/A
N/A
Pre-EC
Worker
0.004
2.8E-03
3.7E-02
50
5.6E-05
7.4E-04
Model
(Probabilistic)
Post-EC
Worker
0.004
2.8E-04
3.7E-03
50
5.6E-06
7.4E-05
Pre-EC
ONU
0.004
1.5E-03
2.1E-02
N/A
N/A
N/A
Post-EC
ONU
0.004
1.5E-04
2.1E-03
Vapor Degreasing, closed-loop
-
Worker
0.004
5.6E-05
7.4E-04
10
5.6E-06
7.4E-05
Model
(Probabilistic)
-
ONU
0.004
3.0E-05
4.2E-04
N/A
N/A
N/A
Cold Cleaning
-
Worker
0.004
6.8E-03
1.5E-02
50
1.4E-04
3.0E-04
Monitoring Data
-
ONU
0.004
4.1E-03
5.3E-03
N/A
N/A
N/A
-
Worker
0.004
8.2E-04
1.8E-02
50
1.6E-05
3.7E-04
Model
(Probabilistic)
-
ONU
0.004
4.3E-04
1.1E-02
N/A
N/A
N/A
Aerosol Degreasing
Pre-EC
Worker
0.004
2.6E-02
6.5E-02
N/A
N/A
N/A
Monitoring Data
Post-EC
Worker
0.004
8.7E-03
1.1E-02
N/A
N/A
N/A
-
Worker
0.004
9.5E-03
3.6E-02
N/A
N/A
N/A
Model
(Probabilistic)
-
ONU
0.004
1.6E-04
1.4E-03
N/A
N/A
N/A
Page 274 of 486
-------
Condition of Use
Category
IUR
(ppnr1)
Cancer Risk
Respirator
APF
Cancer Risk with
Respirator
Exposure Data
Type
Central
tendency
High-end
Central
tendency
High-end
Spray Adhesive
Pre-EC
Sprayer
0.004
2.1E-01
5.2E-01
50
4.2E-03
1.0E-02
Monitoring Data
Post-EC
Sprayer
0.004
2.8E-02
8.6E-02
50
5.7E-04
1.7E-03
Pre-EC
Non-
Sprayer
0.004
2.0E-01
4.3E-01
50
4.0E-03
8.7E-03
Post-EC
Non-
Sprayer
0.004
2.9E-02
5.9E-02
50
5.7E-04
1.2E-03
Pre-EC
ONU
0.004
4.8E-03
2.6E-01
N/A
N/A
N/A
Post-EC
ONU
0.004
3.2E-03
1.1E-02
N/A
N/A
N/A
Dry Cleaning
-
Worker
0.004
4.7E-02
1.0E-01
N/A
N/A
N/A
Monitoring Data
-
ONU
0.004
1.9E-02
4.2E-02
3rd Gen
Spot
Cleaner
0.004
1.6E-03
4.6E-03
Model
(Probabilistic)
3rd Gen
Machine
& Finish
0.004
7.5E-03
3.4E-02
3rd Gen
ONU
0.004
9.7E-04
3.8E-03
4th Gen
Spot
Cleaner
0.004
1.3E-03
3.3E-03
4th Gen
Machine
& Finish
0.004
1.3E-03
3.7E-03
4th Gen
ONU
0.004
6.9E-04
2.4E-03
Spot Cleaning
-
Worker
0.004
1.4E-03
9.7E-03
N/A
N/A
N/A
Monitoring Data
-
Worker
0.004
1.2E-03
2.7E-03
Model
(Probabilistic)
-
ONU
0.004
5.8E-04
1.8E-03
Disposal, Recycling
-
Worker
0.004
6.1E-06
1.2E-04
10
6.1E-07
1.2E-05
Model
(Deterministic)
N/A - Not applicable. EPA believes respirator use is unlikely for workers at small commercial facilities (dry cleaners, spot cleaners) and for occupational non-users.
Page 275 of 486
-------
The range of extra cancer risks calculated for workers in each use category are described in Table
4-49, Figure 4-1 and Figure 4-2. Risk estimates are based on occupational exposure values derived
from monitoring and modeling data (with and without engineering controls). The benchmark
cancer risk estimate of lxlO"4 was exceeded for all of the uses in workers and occupational non-
users for both central tendency and high-end exposure estimates for both monitoring and modeling
data with or without the use an APF in most cases, with few exceptions. These exceptions included
cancer risk estimates when respirators were assumed to be used for: manufacturing, import,
repacking, processing - incorporation into article for the worker; vapor degreasing open-top for the
occupational workers; vapor degreasing closed-loop for workplace exposures; cold cleaning for
workers, and disposal, recycling for the worker. In most cases, benchmark cancer risk estimates
were similar between monitoring and modeling within each use.
Figure 4-1. Central Tendency Inhalation Cancer Risk Estimates for Occupational Use of 1-
BP
Mfg, Worker (Monitoring)
Import, Worker (Model)
Processing - Inc. into Form., Worker (Monitoring)
Processing - Inc. into Form., ONU (Monitoring)
Vapor Degreasing, Open-Top, Worker (Monitoring)
Vapor Degreasing, Open-Top, ONU (Monitoring)
Vapor Degreasing, Open-Top, Worker (Model Pre-EC)
Vapor Degreasing, Open-Top, Worker (Model Post-EC)
Vapor Degreasing, Open-Top, ONU (Model Pre-EC)
Vapor Degreasing, Open-Top, ONU (Model Post-EC)
Vapor Degreasing, Closed-Loop, Worker (Model)
Vapor Degreasing, Closed-Loop, ONU (Model)
Cold Cleaning, Worker (Monitoring)
Cold Cleaning, ONU (Monitoring)
Cold Cleaning, Worker (Model)
Cold Cleaning, ONU (Model)
Aerosol Degreasing, Worker (Monitoring, Pre-EC)
Aerosol Degreasing, Worker (Monitoring, Post-EC)
Aerosol Degreasing, Worker (Model)
Aerosol Degreasing ONU (Model)
Spray Adhesive, Sprayer (Monitoring, Pre-EC)
Spray Adhesive, Sprayer (Monitoring, Post-EC)
Spray Adhesive, Non-Sprayer (Monitoring, Pre-EC)
Spray Adhesive, Non-Sprayer (Monitoring, Post-EC)
Spray Adhesive, ONU (Monitoring, Pre-EC)
Spray Adhesive, ONU (Monitoring, Post-EC)
Dry Cleaning, Worker (Monitoring)
Dry Cleaning, ONU (Monitoring)
Dry Cleaning, Spotter (Model, 3rd Gen)
Dry Cleaning, Machine (Model, 3rd Gen)
Dry Cleaning, ONU (Model, 3rd Gen)
Dry Cleaning, Spotter (Model, 4th Gen)
Dry Cleaning, Spotter (Model, 4th Gen)
Dry Cleaning, Machine (Model, 4th Gen)
Spot Cleaning, Worker (Monitoring)
Spot Cleaning, Worker (Model)
Spot Cleaning, ONU (Model)
Disposal, Worker (Model)
Page 276 of 486
-------
Figure 4-2. High-End Inhalation Cancer Risk Estimates for Occupational Use of 1-BP
l.E-7 l.E-6 l.E-5 l.E-4 l.E-3 l.E-2 l.E-1 1.E+0
4.2.4.3 Cancer Evaluation for Consumer Scenario (Insulation Off-Gassing)
EPA also estimated the excess cancers associated with chronic inhalation exposures under the
insulation (off-gassing) condition of use for the consumer bystander. The excess cancer estimation
for the insulation (off-gassing) condition of use was determined by multiplying the 7-year average
TWA concentration by EPA's inhalation unit risk (IUR) identified in Table 3-6 for human
exposure: 24 hours/day (5.00 E-03, 6.00 E-03, and 9.00 E-03). The supporting calculations are
included in the l-BP_Supplemental FileConsumer Exposure Risk Calculations (EPA 2019c).
ADAFs were not used for younger lifestages due to an inconclusive MMOA (Appendix K).
Page 277 of 486
-------
For consumer bystander exposure, EPA used the following benchmark for determining the
acceptability of the cancer risk:
lxlO"6: the probability of 1 chance in 1 million of an individual developing cancer
Table 4-50 provides a summary of the excess cancer estimates for the Insulation (off-gassing)
condition of use for the consumer bystander. Estimates are provided for all three locations within
each building configuration evaluated for each of the three IURs.
Table 4-50. Inhalation Cancer Risk Estimates Under the Insulation (Off-Gassing) Condition
of Use for the Consumer Bystander
Condition of Use
Scenario Description
Cancer MOE (7-Year Average TWA)
IUR (5.00E-03) IUR (6.00E-03) IUR (9 00E-°3)
Insulation (off-gassing)
A/LS/C
Attic
4.4E-07
2.4E-07 2.9E-07
1.8E-07
9.8E-08 1.2E-07
4.0E-07
2.2E-07 2.7E-07
Living Space
Crawlspace
Insulation (off-gassing)
A/LS/B
Attic
4.3E-07
2.4E-07 2.9E-07
7.1E-08
3.9E-08 4.7E-08
4.2E-07
2.3E-07 2.8E-07
Living Space
Basement
MOE estimates were one to two orders of magnitude smaller than the benchmark MOEs for each
location within each building configuration.
4.2.5 Risk Characterization For Acute and Chronic, Non-Cancer and Cancer
Dermal Exposures
For dermal exposure, conditions of use with similar exposure concentration, exposure level, and
potential for occlusion are "binned" as described in Section 2.3.1.23 for occupational exposures.
MOE estimates for occupational conditions of use (Bins 1-5) following acute and chronic dermal
exposures based on modeling and what-if glove protection factors are presented in Table 4-51,
Table 4-52, Table 4-53, Table 4-54 and Table 4-55. Cancer risk estimates for these same
conditions of use following chronic dermal exposures are presented in Table 4-56.
Page 278 of 486
-------
Use: Manufacture, Import, Processing, and Disposal (Bin 1)
MOE estimates for manufacture, import, processing, and disposal activities for both acute and chronic dermal exposure scenarios are
presented in Table 4-51.
Table 4-51. Non-Cancer Risk Estimates for Acute and Chronic Dermal Exposures Following Occupational Use of 1-BP in
Manufacture, Import, Processing, and Disposal (Bin 1, Benchmark = 100)
Exposure
Duration for
Risk Analysis
Target Organ/
System
HED
(mg/kg-day)
Exposure Level
No Gloves
(PF = 1)
Protective
Gloves
(PF = 5)
Protective
Gloves
(PF = 10)
Protective
Gloves
(PF = 20)
Develop, (litter size)
19
Central tendency
700
3,499
6,998
13,996
Acute, Non-
High-end
233
1,166
2,333
4,665
Cancer
Develop, (post-impl.
11
Central tendency
405
2,026
4,051
8,103
loss)
High-end
135
675
1,350
2,701
Liver
95
Central tendency
3,499
17,495
34,989
69,978
High-end
1,166
5,832
11,663
23,326
Kidney
115
Central tendency
4,236
21,178
42,355
84,711
High-end
1,412
7,059
14,118
28,237
Reproductive
33
Central tendency
1,215
6,077
12,154
24,308
Chronic, Non-
System
High-end
405
2,026
4,051
8,103
Cancer
Develop, (litter size)
19
Central tendency
982
4,912
9,824
19,648
High-end
327
1,637
3,275
6,549
Develop, (post-impl.
11
Central tendency
569
2,844
5,688
11,375
loss)
High-end
190
948
1,896
3,792
Nervous System
16
Central tendency
589
2,946
5,893
11,786
High-end
196
982
1,964
3,929
Page 279 of 486
-------
MOE estimates for Manufacture, Import, Processing, and Disposal (Bin 1) were above the benchmark MOE by 1-2 orders of magnitude in
all acute and chronic exposure scenarios for all health effect endpoints when no gloves were used (PF=1). As the PF increased, MOE
estimates continued to increase above the benchmark MOE in both acute and chronic exposure scenarios for all health effect endpoints.
Use: Vapor Degreaser and Cold Cleaner (Bin 2)
MOE estimates for vapor degreaser and cold cleaner conditions of use for both acute and chronic exposure scenarios are presented in Table
4-52.
Table 4-52. Non-Cancer Risk Estimates for Acute and Chronic Dermal Exposures Following Occupational Use of 1-BP in Vapor
Degreaser and Cold Cleaner (Bin 2, Benchmark = 100)
Exposure
Duration for
Risk Analysis
Target Organ/
System
HEP
(mg/kg-day)
Exposure Level
No Gloves
(PF = 1)
Protective
Gloves
(PF = 5)
Protective
Gloves
(PF = 10)
Protective
Gloves
(PF = 20)
Develop, (litter size)
19
Central tendency
721
3,607
7,214
14,429
Acute, Non-
High-end
240
1,202
2,405
4,810
Cancer
Develop, (post-impl.
11
Central tendency
418
2,088
4,177
8353
loss)
High-end
139
696
1,392
2,784
Liver
95
Central tendency
3,607
18,036
36,071
72,143
High-end
1,202
6,012
12,024
24,048
Kidney
115
Central tendency
4,367
21,833
43,665
87,331
High-end
1,456
7,278
14,555
29,110
Reproductive
33
Central tendency
1,253
6,265
12,530
25,060
Chronic, Non-
System
High-end
418
2,088
4,177
8,353
Cancer
Develop, (litter size)
19
Central tendency
1,013
5,064
10,128
20,255
High-end
338
1,688
3,376
6,752
Develop, (post-impl.
11
Central tendency
586
2,932
5,863
11,727
loss)
High-end
195
977
1,954
3,909
Nervous System
16
Central tendency
608
3,038
6,075
12,150
High-end
203
1,013
2,025
4,050
Page 280 of 486
-------
MOE estimates for vapor degreaser and cold cleaner conditions of use were above the benchmark MOE by 1-2 orders of magnitude in all
acute and chronic exposure scenarios for all health effect endpoints when no gloves were used (PF=1). As the PF increased, MOE estimates
continued to increase above the benchmark MOE in both acute and chronic exposure scenarios for all health effect endpoints.
Use: Spray Adhesive (Bin 3)
MOE estimates for spray adhesive conditions of use for both acute and chronic exposure scenarios are presented in Table 4-53.
Table 4-53. Non-Cancer Risk Estimates for Acute and Chronic Dermal Exposures Following Occupational Use of 1-BP in Spray
Adhesive (Bin 3, Benchmark = 100)
Exposure
Duration for
Risk Analysis
Target Organ/
System
HEP
(mg/kg-day)
Exposure Level
No Gloves
(PF = 1)
Protective
Gloves
(PF = 5)
Protective
Gloves
(PF = 10)
Protective
Gloves
(PF = 20)
Develop, (litter size)
19
Central tendency
875
4,374
8,747
Acute, Non-
High-end
292
1,458
2,916
Cancer
Develop, (post-impl.
11
Central tendency
506
2,532
5,064
loss)
High-end
169
844
1,688
Liver
95
Central tendency
4,374
21,868
43,736
High-end
1,458
7,289
14,579
Kidney
115
Central tendency
5,294
26,472
52,944
High-end
1,765
8,824
17,648
Reproductive
33
Central tendency
1,519
7,596
15,193
N/A
Chronic, Non-
System
High-end
506
2,532
5,064
Cancer
Develop, (litter size)
19
Central tendency
1,228
6,140
12,280
High-end
409
2,047
4,093
Develop, (post-impl.
11
Central tendency
711
3,555
7,109
loss)
High-end
237
1,185
2,370
Nervous System
16
Central tendency
737
3,683
7,366
High-end
246
1,228
2,455
Page 281 of 486
-------
MOE estimates for spray adhesive conditions of use were above the benchmark MOE by 1-2 orders of magnitude in all acute and chronic
exposure scenarios for all health effect endpoints when no gloves were used (PF=1). As the PF increased, MOE estimates continued to
increase above the benchmark MOE in both acute and chronic exposure scenarios for all health effect endpoints.
Use: Dry Cleaning and Spot Cleaner (Bin 4)
MOE estimates for dry cleaning and spot cleaner conditions of use for both acute and chronic exposure scenarios are presented in Table
4-54.
Table 4-54. Non-Cancer Risk Estimates for Acute and Chronic Dermal Exposures Following Occupational Use of 1-BP in Dry
Cleaning and Spot Cleaner (Bin 4, Benchmark = 100)
Exposure
Duration for
Risk Analysis
Target Organ/
System
HEP
(mg/kg-day)
Exposure Level
No Gloves
(PF = 1)
Protective
Gloves
(PF = 5)
Protective
Gloves
(PF = 10)
Protective
Gloves
(PF = 20)
Develop, (litter size)
19
Central tendency
744
3,722
7,445
Acute, Non-
High-end
248
1,241
2,482
Cancer
Develop, (post-impl.
11
Central tendency
431
2,155
4,310
loss)
High-end
144
718
1,437
Liver
95
Central tendency
3,722
18,611
37,223
High-end
1,241
6,204
12,408
Kidney
115
Central tendency
4,236
21,178
42,355
High-end
1,412
7,059
14,118
N/A
Reproductive
33
Central tendency
1,293
6,465
12,930
Chronic, Non-
System
High-end
431
2,155
4,310
Cancer
Develop, (litter size)
19
Central tendency
1,045
5,225
10,451
High-end
348
1,742
3,484
Develop, (post-impl.
11
Central tendency
605
3,025
6,051
loss)
High-end
202
1,008
2,017
Nervous System
16
Central tendency
627
3,135
6,269
High-end
209
1,045
2,090
Page 282 of 486
-------
MOE estimates for dry cleaning and spot cleaner conditions of use were above the benchmark MOE by 1-2 orders of magnitude in all acute
and chronic exposure scenarios for all health effect endpoints when no gloves were used (PF=1). As the PF increased, MOE estimates
continued to increase above the benchmark MOE in both acute and chronic exposure scenarios for all health effect endpoints.
Use: Aerosol Spray Degreaser/Cleaner, Other Aerosol and Non-aerosol Uses (Bin 5)
MOE estimates for aerosol spray degreaser/cleaner, and other aerosol and non-aerosol conditions of use for both acute and chronic exposure
scenarios are presented in Table 4-55.
Table 4-55. Non-Cancer Risk Estimates for Acute and Chronic Dermal Exposures Following Occupational Use of 1-BP in Aerosol
Spray Degreaser/Cleaner, Other Aerosol and Non-aerosol Uses (Bin 5, Benchmark = 100)
Exposure
Duration for
Risk Analysis
Target Organ/
System
HED
(mg/kg-day)
Exposure Level
No Gloves
(PF = 1)
Protective
Gloves
(PF = 5)
Protective
Gloves
(PF = 10)
Protective
Gloves(PF = 20)
Develop, (litter size)
19
Central tendency
700
3,499
6,998
Acute, Non-
High-end
233
1,166
2,333
Cancer
Develop, (post-impl.
11
Central tendency
405
2,026
4,051
loss)
High-end
135
675
1,350
Liver
95
Central tendency
3,499
17,495
34,989
High-end
1,166
5,832
11,663
Kidney
115
Central tendency
4,236
21,178
42,355
High-end
1,412
7,059
14,118
Reproductive
33
Central tendency
1,215
6,077
12,154
N/A
Chronic, Non-
System
High-end
405
2,026
4,051
Cancer
Develop, (litter size)
19
Central tendency
982
4,912
9,824
High-end
327
1,637
3,275
Develop, (post-impl.
11
Central tendency
569
2,844
5,688
loss)
High-end
190
948
1,896
Nervous System
16
Central tendency
589
2,946
5,893
High-end
196
982
1,964
Page 283 of 486
-------
MOE estimates aerosol spray degreaser/cleaner, and other aerosol and non-aerosol conditions of use were above the benchmark MOE by 1-
2 orders of magnitude in all acute and chronic exposure scenarios for all health effect endpoints when no gloves were used (PF=1). As the
PF increased, MOE estimates continued to increase above the benchmark MOE in both acute and chronic exposure scenarios for all health
effect endpoints.
Use: Bins 1-5
Cancer risk estimates for occupational conditions of use (category Bins 1-5) are presented in Table 4-56.
Table 4-56. Cancer Risk Estimates for Dermal Exposure Following Occupational Use of 1-BP
Category
Dermal Slope
Factor
(mg/kg-day)1
Exposure Level
No Gloves
(PF = 1)
Protective
Gloves
(PF = 5)
Protective
Gloves
(PF = 10)
Protective
Gloves
(PF = 20)
Benchmark
Bin 1: Manufacture,
Import, Proc
0.006
Central tendency
6.47E-05
1.29E-05
6.47E-06
3.24E-06
1E-04
High-end
2.51E-04
5.01E-05
2.51E-05
1.25E-05
Bin 2: Degreasing
and cold cleaning
Central tendency
6.28E-05
1.26E-05
6.28E-06
3.14E-06
1E-04
High-end
2.43E-04
4.86E-05
2.43E-05
1.22E-05
Bin 3: Spray
adhesives
Central tendency
5.18E-05
1.04E-05
5.18E-06
N/A
1E-04
High-end
2.01E-04
4.01E-05
2.01E-05
N/A
Bin 4: Dry cleaning,
spot cleaning
Central tendency
6.09E-05
1.22E-05
6.09E-06
N/A
1E-04
High-end
2.36E-04
4.71E-05
2.36E-05
N/A
Bin 5: Aerosol spray
degreaser. Other
aerosol and non-
aerosol uses
Central tendency
6.47E-05
1.29E-05
6.47E-06
N/A
1E-04
High-end
2.51E-04
5.01E-05
2.51E-05
N/A
The benchmark cancer risk estimate (lxlO"4) was exceeded for all conditions of use in the high-end scenario (Bins 1-5) when no gloves
were used (PF=1); however, as the PF increased between 5 and 20, the benchmark cancer risk estimate (lxlO"4) was not exceeded.
Consumer MOE Estimates for Acute, Non-Cancer Dermal Exposure
MOE estimates for acute, non-cancer consumer dermal exposures were derived for all conditions of use except the insulation (off-gassing)
condition of use. Table 4-57 provides a summary of acute, non-cancer consumer dermal exposure for the eight conditions of use evaluated
Page 284 of 486
-------
for dermal exposure. The supporting calculations are included in the 1-BPSupplemental FileConsumer Exposure Risk Calculations (EPA.
2019c)
Table 4-57. Non-Cancer Risk Estimates for Acute 24-hr Dermal Exposure Following Consumer Uses of 1-BP
Developmental Effects
Developmental Effects
Decreased live litter size (Fi)
Post-Implantation Loss (F0)
Condition of Use
Scenario Description
(WIL Research. 2001)
(WIL Research. 2001)
HED =19 mg/kg-day
HED =11 mg/kg-day
Adult
Youth A
Youth B
Adult
Youth A
Youth B
Aerosol spray degreaser/cleaner-general
High Intensity Use
5.4
5.8
5.3
3.1
3.3
3.1
Moderate Intensity Use
83
86
79
48
50
46
Low Intensity Use
1118
1188
1118
647
688
647
Aerosol spray degreaser/cleaner-electronic
High Intensity Use
413
442
404
239
256
234
Moderate Intensity Use
559
594
543
324
344
314
Low Intensity Use
792
864
792
458
500
458
Spot cleaner and stain remover
High Intensity Use
22
23
21
13
14
12
Moderate Intensity Use
209
224
204
121
129
118
Low Intensity Use
4419
4634
4318
2558
2683
2500
Coin and scissors cleaner
High Intensity Use
250
268
247
145
155
143
Moderate Intensity Use
500
543
487
289
314
282
Low Intensity Use
1462
1583
1462
846
917
846
Spray cleaner-general
High Intensity Use
5.3
5.8
5.3
3.1
3.3
3.1
Moderate Intensity Use
43
45
42
25
26
24
Low Intensity Use
322
345
311
186
200
180
Adhesive accelerant
High Intensity Use
396
422
388
229
244
224
Moderate Intensity Use
396
422
388
229
244
224
Low Intensity Use
396
422
388
229
244
224
Automobile AC flush
High Intensity Use
38
40
37
22
23
21
Moderate Intensity Use
38
40
37
22
23
21
Low Intensity Use
38
40
37
22
23
21
Mold cleaning and release products
High Intensity Use
442
475
432
256
275
250
Moderate Intensity Use
679
731
655
393
423
379
Low Intensity Use
1267
1357
1267
733
786
733
Page 285 of 486
-------
MOE estimates were below the benchmark MOE of 100 for four of the eight conditions of use evaluated. Generally, MOE estimates were
one to two orders of magnitude lower than the benchmark MOE.
Page 286 of 486
-------
4.3 Assumptions and Key Sources of Uncertainty
The characterization of variability and uncertainty is fundamental to any risk evaluation.
Variability refers to "the true heterogeneity or diversity in characteristics among members of a
population {i.e., inter-individual variability) or for one individual over time (intra-individual
variability)" (U.S. EPA. 2001). The risk evaluation was designed to reflect critical sources of
variability to the extent allowed by available methods and data and given the resources and time
available.
On the other hand, uncertainty is "the lack of knowledge about specific variables, parameters,
models, or other factors" (U.S. EPA. 2001) and can be described qualitatively or quantitatively.
Uncertainties in the risk evaluation can raise or lower the confidence of the risk estimates. In this
assessment, the uncertainty analysis also included a discussion of data gaps/limitations. The next
sections describe the uncertainties and data gaps in the exposure, hazard/dose-response and risk
characterization.
One key uncertainty is whether the human populations that are at the greatest risk, based on the
integration of information regarding highly exposed groups (or "potentially exposed") and
biologically susceptible subpopulations, have been adequately defined and characterized. Workers
and ONUs who are also biologically susceptible individuals (e.g., reproductive age men and
women, pregnant women and their fetus, and adolescent workers) would represent the most
susceptible population. Consumers (product users) and bystanders who are biologically susceptible
individuals would also represent the most susceptible populations Analyses have been performed
to understand the risk for the identified potentially susceptible populations.
4.3.1 Uncertainties of the Occupational Exposure Assessment
EPA addressed variability in the exposure models by identifying key model parameters to apply a
statistical distribution that mathematically defines the parameter's variability. EPA defined
statistical distributions for parameters using documented statistical variations where available.
Where the statistical variation is not known, assumptions are made to estimate the parameter
distribution using available literature data. See the Supplemental Information on Occupational
Exposure Assessment (EPA. 2019f) for statistical distribution for each model input parameter. The
following sections discuss uncertainties in the occupational exposure assessment.
One overarching uncertainty is that exposures to 1-BP from outside the workplaces are not
included in the occupational assessment, which may lead to an underestimate of occupational
exposure. Another overarching uncertainty is that inhalation and dermal exposures were assessed
separately, which may also lead to an underestimation of occupational exposure.
Page 287 of 486
-------
4.3.1.1 Number of Workers
There are a number of uncertainties surrounding the estimated number of workers potentially
exposed to 1-BP, as outlined below. Most are unlikely to result in a systematic underestimate or
overestimate, but could result in an inaccurate estimate.
CDR data are used to estimate the number of workers associated with the following conditions of
use: Manufacturing, Import, Processing as a Reactant, and Incorporation into Formulation,
Mixture, or Reaction Product. There are inherent limitations to the use of CDR data. First,
manufacturers and importers are only required to report if they manufactured or imported 1-BP in
excess of 25,000 pounds at a single site during any calendar from 2012 to 2015; as such, CDR may
not capture all sites and workers associated with any given chemical. Second, the estimate is based
on information that is known or reasonably ascertainable to the submitter. CDR submitters
(chemical manufacturers and importers) do not always have accurate information on the number of
potentially exposed workers at downstream processing sites.
There are also uncertainties associated with BLS data, which are used to estimate the number of
workers for the remaining conditions of use. First, BLS' OES employment data for each
industry/occupation combination are only available at the 3-, 4-, or 5-digit NAICS level, rather
than the full 6-digit NAICS level. This lack of granularity could result in an overestimate of the
number of exposed workers if some 6-digit NAICS are included in the less granular BLS estimates
but are not, in reality, likely to use 1-BP for the assessed condition of use. EPA addressed this issue
by refining the OES estimates using total employment data from the U.S. Census' SUSB.
However, this approach assumes that the distribution of occupation types (SOC codes) in each 6-
digit NAICS is equal to the distribution of occupation types at the parent 5-digit NAICS level. If
the distribution of workers in occupations with 1-BP exposure differs from the overall distribution
of workers in each NAICS, then this approach will result in inaccuracy.
Second, EPA's judgments about which industries (represented by NAICS codes) and occupations
(represented by SOC codes) are associated with the uses assessed in this report are based on EPA's
understanding of how 1-BP is used in each industry. Designations of which industries and
occupations have potential exposures is nevertheless subjective, and some industries/occupations
with few exposures might erroneously be included, or some industries/occupations with exposures
might erroneously be excluded. This would result in inaccuracy but would be unlikely to
systematically either overestimate or underestimate the count of exposed workers.
4.3.1.2 Analysis of Occupational Exposure Monitoring Data
To analyze exposure monitoring data, EPA categorized individual PBZ data point as either
"worker" or "occupational non-user." Exposures for occupational non-users can vary substantially.
Most data sources do not sufficiently describe the proximity of these employees to the 1-BP
exposure source. As such, exposure levels for the "occupational non-user" category will have high
variability depending on the specific work activity performed. It is possible that some employees
Page 288 of 486
-------
categorized as "occupational non-user" have exposures similar to those in the "worker" category
depending on their specific work activity pattern.
Some data sources may provide exposure estimates that are higher than typical across the
distribution of facilities for that condition of use. For example, NIOSH HHEs for the spray
adhesive use were conducted to address concerns regarding adverse human health effects reported
following 1-BP exposure with spray adhesive use in furniture manufacturing. Two HHEs were
requested by the North Carolina Department of Labor; one was conducted in response to a
confidential request submitted by the facility's employees.
There are limited exposure monitoring data in literature for certain conditions of use or job
categories. For example, very few data points are available for cold cleaning and for spot-cleaning.
Where few data are available, the assessed exposure levels are unlikely to be representative of
worker exposure across the entire job category or industry. In addition, exposure data for
compliance safety and health officers may not be representative of typical exposure levels for
occupational non-users.
For vapor degreasing and cold cleaning, several sources do not contain detailed information
describing the type of degreaser or cleaner present at the facility. The lack of such information
results in uncertainty in the assessed exposure levels associated with specific subcategories of such
equipment. For example, the data presented for batch open-top vapor degreasers may actually
include data associated with other types of degreaser.
Where the sample data set contains six or more data points, the 50111 and 95th percentile exposure
concentrations were calculated from the sample to represent central tendency and high-end
exposure levels. The underlying distribution of the data, and the representativeness of the available
data, are not known.
4.3.1.3 Near-Field / Far-Field Model Framework
The near-field / far-field approach is used as a framework to model inhalation exposure for many
conditions of use. The following describe uncertainties and simplifying assumptions generally
associated with this modeling approach:
• There is 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 but may not
accurately reflect actual distribution of the input parameters.
• The model assumes the near-field and far-field are each well mixed, such that each of these
zones can be approximated by a single, average concentration.
Page 289 of 486
-------
• All of the emissions from the facility are assumed to enter the near-field zone. This
assumption will overestimate exposures and risks in facilities where some of the emissions
do not enter the airspaces relevant to the worker exposure modeling.
• The exposure models estimate airborne concentrations. Exposures 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). Since vapor
degreasing and cold cleaning involve automated processes, a worker may actually walk
away from the near-field during part of the process and return when it is time to unload the
degreaser. As such, assuming the worker is exposed at the near-field concentration for the
entire activity duration may overestimate exposure. Conversely, assuming the occupational
non-user is exposed at the far-field concentration for the entire work day may
underestimate exposure as they may not remain exclusively in the far-field.
• For certain 1-BP applications {e.g., vapor degreasing and cold cleaning), 1-BP vapor is
assumed to emit continuously while the equipment operates {i.e., constant vapor generation
rate). Actual vapor generation rate may vary with time. However, small time variability in
vapor generation is unlikely to have a large impact in the exposure estimates as exposures
are calculated as a time-weighted average.
• The exposure models represent model workplace settings for each 1-BP condition of use.
The models have not been regressed or fitted with monitoring data.
• The models represent a baseline scenario that do not have LEV. EPA does not have
adequate data to construct LEV systems into the exposure models. Additionally, there is no
data on the fraction of U.S. facilities that use LEV. Where available, "what-if' values on
engineering control effectiveness are applied to the model baseline to provide post-EC
scenarios. These values were obtained by reviewing statements made in published literature
regarding potential emission or exposure reductions after implementation of engineering
control or equipment substitution.
Each subsequent section below discuss uncertainties associated with the individual models.
4.3.1.4 Vapor Degreasing and Cold Cleaning Model
The vapor degreasing and cold cleaning assessments use a near-field / far-field approach to model
worker exposure. In addition to the uncertainties described above, the vapor degreasing and cold
cleaning models have the following uncertainties:
• To estimate vapor generation rate for vapor degreasing, EPA references a 1-BP emission
factor developed by CARB for the California Solvent Cleaning Emissions Inventories
(CARB. 2011). The emission factor is an average emission for the "vapor degreasing"
category for the California facilities surveyed by CARB. The category includes batch-
loaded vapor degreaser, aerosol surface preparation process, and aerosol cleaning process.
For the purpose of modeling, EPA assumes the 1-BP emission factor is entirely attributed
to vapor degreasing applications. The representativeness of the emission factor for vapor
degreasing emissions in other geographic locations within the U.S. is uncertain.
Page 290 of 486
-------
• The CARB emission factor covers batch degreasing units. However, CARB does not
further specify whether these are open-top vapor degreasers, enclosed, or other types of
batch degreasers. EPA assumes the emission factor is representative of open-top vapor
degreaser, as it is the most common design for batch units using 1-BP. In addition, EPA
assumes that the surveyed facilities likely switched to using 1-BP, an alternative, non-HAP
solvent, as a way of complying with Federal and State regulations for HAP halogenated
solvents {i.e., chemical substitution, rather than equipment changes).
• The CARB emission factor, in the unit of pound per employee-year, was developed for the
purpose of estimating annual emissions. These types of emission factor typically reflect the
amount of solvent lost / emitted, some of which may not be relevant to worker exposure.
For example, 1-BP emitted and captured through a stack may not result in worker exposure.
Therefore, assuming all of the 1-BP is emitted into the workplace air may result in
overestimating of exposure. In addition, the use of an annual emission factor does not
capture time variability of emissions. The approach assumes a constant emission rate over a
set number of operating hours, while actual emissions and worker exposures will vary as a
function of time and worker activity.
• EPA combines the CARB emission factor with nationwide Economic Census employment
data across 78 NAICS industry sector codes. It should be noted that vapor degreasing is not
an industry-specific operation. Only a subset of facilities within the 78 selected industry
sectors are expected to operate vapor degreasers. Therefore, the industry-average
employment data may not be representative of the actual number of employees at vapor
degreasing facilities.
• To estimate worker exposure during cold cleaning, EPA applied an emission reduction
factor to the vapor degreasing model by comparing the AP-42 emission factors for the two
applications. The AP-42 emission factors are dated. Furthermore, the cold cleaning model
results have not been validated with actual monitoring data.
• EPA assumes workers and occupational non-users remove themselves from the
contaminated near- and far-field zones at the conclusion of the task, such that they are no
longer exposed to any residual 1-BP in air.
• The model assumes an exposure reduction of 90 percent with engineering controls. In
reality, engineering controls and their effectiveness are site-specific. Additionally, the 90
percent reduction is a value based on TCE, and may not be applicable to a more volatile
chemical such as 1-BP.
4.3.1.5 Aerosol Degreasing Model
The aerosol degreasing assessment also uses a near-field/far-field approach to model worker
exposure. Specific uncertainties associated with the aerosol degreasing scenario are presented
below:
• The model references a CARB (2000) study 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 1-BP.
Page 291 of 486
-------
• The Use Dossier (U.S. EPA. 2017c) identifies 25 different aerosol degreasing formulations
containing 1-BP. For each Monte Carlo iteration, the model determines the 1-BP
concentration in product by selecting one of 25 possible formulations, assuming equal
probability of each formulation being used. In reality, some formulations are likely more
prevalent than others.
4.3.1.6 Dry Cleaning Model
The multi-zone dry cleaning model also uses a near-field/far-field approach. Specific uncertainties
associated with the dry cleaning scenario are presented below:
• The model assumes each facility only has one dry cleaning machine, cleaning one to
fourteen loads of garments per day. While the dry cleaning facilities in Blando et al. (2010)
and NIOSH (2010) appear to only have one machine, the representativeness of these two
studies is not known. Larger facilities are likely to have more machines, which could result
in additional 1-BP exposures.
• The model conservatively uses a hemispherical volume based on the dry cleaning machine
door diameter as the near-field for machine unloading. The small near-field volume results
in a large spike in concentration when the machine door is opened, where any residual 1-BP
solvent is assumed to be instantaneously released into the near-field. In reality, the residual
solvent will likely be released continuously over a period of time. In addition, the worker
may move around while unloading the garments, such that the worker's breathing zone will
not always be next to the machine door throughout the duration of this activity. Therefore,
these assumptions may result in an overestimate of worker exposure during machine
unloading.
• Many of the model input parameters were obtained from (Von Grote et al.. 2003). which is
a German study. Aspects of the U.S. dry cleaning facilities may differ from German
facilities. However, it is not known whether the use of German data will under- or over-
estimate exposure.
• The model does not cover all potential worker activities at dry cleaners. For example,
workers could be exposed to 1-BP emitted due to equipment leaks, when re-filling 1-BP
solvent into dry cleaning machines, when interrupting a dry cleaning cycle, or when
performing maintenance activities (e.g., cleaning lint and button traps, raking out the still,
changing solvent filter, and handling solvent waste) (OSHA. 2005). However, there is a
lack of information on these activities in the literature, and the frequency of these activities
is not well understood. The likelihood of equipment leaks is dependent on whether the
machines are properly converted and maintained. The frequency of solvent re-filling
depends on a specific dry cleaner's workload and solvent consumption rate, which is also
affected by the presence of leaks. Based on observations reported by (NIOSH. 2010) and
(Blando et al.. 2010). solvent charging is not performed every day. EPA was unable to
develop a modeling approach for these exposure activities due to the lack of available
information.
Page 292 of 486
-------
4.3.1.7 Spot Cleaning Model
The spot cleaning assessment also uses a near-field/far-field approach to model worker exposure.
The model estimates a use rate of 16 gallons per year spot cleaner. This value was derived using a
MassDEP case study for one specific dry cleaner in Massachusetts, handling 100 pieces of
garments per day. MassDEP noted that the size of each dry cleaner can vary substantially. As such,
the spot cleaner use rate will also vary by the individual facility work load. The representativeness
of the spot cleaner use rate from this case study is not known.
4.3.1.8 Tank Truck and Railcar Loading and Unloading Release and
Inhalation Exposure Model
For Import/repackaging, Processing as a reactant, and Processing - Incorporation into articles, the
Tank Truck and Railcar Loading and Unloading Release and Inhalation Exposure Model is 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 1-BP 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 published in the OPW Engineered
Systems catalog and engineering judgment. These dimensions may not be
representativeness of the whole range of loading equipment used at industrial facilities
handling 1-BP.
• The model estimates fugitive emissions from equipment leaks using total organic
compound emission factors from EPA's Protocol for Equipment Leak Emission Estimates
(1995), and engineering judgement on the likely equipment type used for transfer (e.g.,
number of valves, seals, lines, and connections). The applicability of these emission factors
to 1-BP, and the accuracy of EPA's assumption on equipment type are not known.
• The model assumes the use a vapor balance system to minimize fugitive emissions.
Although most industrial facilities are likely to use a vapor balance system when
loading/unloading volatile chemicals, EPA does not know whether these systems are used
by all facilities that potentially handle 1-BP.
4.3.1.9 Modeling Dermal Exposures
The Dermal Exposure to Volatile Liquids Model is used to estimate dermal exposure to 1-BP in
occupational settings. The model assumes a fixed fractional absorption of the applied dose;
however, fractional absorption may be dependent on skin loading conditions. The model also
assumes a single exposure event per day based on existing framework of the EPA/OPPT 2-Hand
Dermal Exposure to Liquids Model and does not address variability in exposure duration and
frequency.
The model accounts for potential glove use by presenting the dermal dose estimates using several
what-if values for glove protection factor (PF). These PF values depend on whether the glove is
chemically resistant, and whether the employee has received training on glove use. It should be
Page 293 of 486
-------
noted that PF values are not chemical-specific, and using PF values to adjust the dermal dose may
either under- or over-estimate actual exposure. For example, assumption of certain glove PF value
may underestimate exposure as 1-BP easily penetrates most common glove materials. In addition,
incorrect glove use may lead to glove contamination or occluded exposure, resulting in higher
exposure than when gloves are not used. In this case, actual PF value may be less than one.
4,3,2 Uncertainties of the Consumer Exposure Assessment
Modeling was used to evaluate consumer exposure concentrations resulting from the use of the
following consumer products containing 1-BP: aerosol spray degreaser/cleaner-general; aerosol
spray degreaser/cleaner-electronics, spot cleaner and stain remover, coin and scissors cleaner,
spray cleaner-general, adhesive accelerant, automobile AC flush, mold cleaning and release
product, and insulation (off-gassing). Inputs for this modeling approach relied on default values
(based on experimental data) within the models used, survey information, and various assumptions.
As with any approach to risk evaluations, there are uncertainties associated with the assumptions,
data used, and approaches used. These are discussed in detail within Section 2.3.2.
4.3.2.1 Consumer Use Information
The consumer use dossier and market profile documents (U.S. EPA. 2017c) were developed in
2016 and 2017 based on information reasonably available at that time. These do not take into
consideration company-initiated formulation changes, product discontinuation, or other business or
market based factors occurring after the documents were compiled. While there may be some
uncertainty associated with products identified in 2016 and 2017 remaining readily available, EPA
believes the information utilized to identify the consumer uses is the best available information.
EPA found national survey information related to use of household products containing solvents
(EPA. 1987) that was compiled in 1987. While this survey is an older survey, many of the product
categories within the survey align well with the consumer conditions of use identified for this
evaluation. Additionally, the consumer use profiles and patterns evaluated by the survey remain
strong when compared to modern day consumer use patterns even though some aspects of the use
may have changed. Regardless of these similarities and strengths, EPA realizes there is still some
level of uncertainty associated with the survey data and its application to modern day consumer use
patterns, amount used, or duration of use. While some level of uncertainty remains, the approach
taken for this evaluation to vary key inputs across the spectrum of use patterns captured by the
survey should reduce the uncertainties.
The frequency of use values extracted from the Westat Survey (EPA. 1987) and utilized for
consumer modeling were assumed to be infrequent, non-consecutive time periods and therefore not
expected to create risk concerns for chronic exposure scenarios (with the exception of insulation in
residential homes). However, it is unknown whether frequency of use patterns are expected to be
clustered or intermittent and how this type of exposure would compare to continuous-exposure
toxicity studies. Therefore, while EPA cannot fully rule out the possibility that consumers at the
high-end frequencies of use could be at risk for chronic hazard effects, it is expected to be unlikely.
Page 294 of 486
-------
4.3.2.2 Model Assumptions and Input Parameters
Inhalation Models and Results
There is a high confidence in the three models used to evaluate inhalation exposure and the
inhalation results found for the conditions of use identified in Table 2-31. This confidence derives
from a review of the strengths of the models used, sensitivity of the models, data and inputs
utilized for modeling, and approaches taken for this evaluation to capture a range of consumer use
patterns.
Dermal Models and Results
There is a low confidence in the two models used to evaluate dermal exposure and the dermal
results found for the conditions of use identified in Table 2-31. This confidence derives from the
limitations and uncertainties inherent within the two dermal models selected and associated
assumptions necessary to correctly apply the two models to the conditions of use evaluated and the
consumer use patterns considered for consumer exposure. The switch from an aqueous based Kp
value to a neat Kp value, along with use of a neat permeability coefficient and experimental
absorption coefficient increases the confidence in the dermal results presented. Additional
discussion on limitations and uncertainties along with a sensitivity analysis comparing the two
methods selected and a third method published by Frasch (Frasch and Bunge. 2015) is provided in
Appendix F.
There is a high degree of confidence in the consumer product weight fractions identified for the
consumer products evaluated in this assessment. Product weight fractions were obtained from
product specific SDS and when a range of weight fractions exists across several products within a
single condition of use evaluated, modeling was conducted across the range of weight fractions
capturing a low, moderate, and high weight fraction value.
There is a high degree of confidence in inputs to the various models used , including vapor
pressure, molecular weight, room volumes, whole house volume, and air exchange rate. The
physical-chemical properties of 1-BP are well documented and therefore have a high degree of
confidence. The room and house volumes as well as air exchange rates are based on values from
U.S. EPA's Exposure Factors Handbook (U.S. EPA. 2011) and therefore also have a high degree
of confidence.
4.3.3 Uncertainties in the Hazard and Dose-Response Assessments
EPA's risk assessment relied on the hazard values {i.e., HECs/HEDs/ADAFs) derived in this
evaluation. These hazard values were used to estimate risks to various health effects following 1-BP
exposure related to specific 1-BP uses.
There are several uncertainties inherent to the data and the assumptions used to support the
derivation of the acute and chronic non-cancer PODs for different health effects domains. Below is
a summary of the major uncertainties affecting the non-cancer hazard/dose response approach used
for this assessment.
Page 295 of 486
-------
The uncertainties in hazard and dose response assessment are predicated on the health protective
assumptions of relevancy of cancer and non-cancer findings in rodents being relevant to humans.
Decreased live litter size was selected as an endpoint to evaluate risks associated with acute
exposures to 1-BP. Although the developmental toxicity studies included repeated exposures, EPA
considered evidence that a single exposure to a toxic substance can result in adverse developmental
effects, described by (Van Raaii et al.. 2003). as relevant to 1-BP. The selection of an endpoint
from a short-term developmental exposure study is a health protective assumption stated in the
EPA Guidelines for Developmental Toxicity Risk Assessment
(https://www.epa.gov/risk/guidelines-developmental-toxicitv-risk-assessment).
Although there is evidence of biological effects in both the fetus and neonate, there are
uncertainties in extrapolating doses for these lifestages. It is not known if 1-BP or its metabolites
are transferred to the pups via lactation. It is possible that the doses reaching the fetus and the
neonate are similar and that these lifestages are equally sensitive; however, it is also possible that
one lifestage is more sensitive than the other or that internal doses are different. Additional data
would be needed to refine dose estimates for the fetus and pups in order to identify the specific
windows of sensitivity. EPA assumes that a single exposure at any point during pregnancy can
have a detrimental impact (leading to fetal mortality). This health protective approach will
overestimate risks to the workers and consumers following acute exposures, especially for those
lifestages below reproductive age.
Neurotoxicity produced by 1-BP are based on rodent and human literature, with considerable
similarities in both qualitative and quantitative outcomes (Appendix J.2 and J.3). In the human and
rodent literature, the most consistent responses are symptoms of frank neurotoxicity occurring at
high exposures, with effects that are progressive at repeated exposures to low concentrations. In
humans, the reports of effects in factory workers with lower exposures are limited by questions
regarding exposure characterization, measurement techniques, and sensitivity. For these reasons,
the data are not sufficiently robust for quantitative dose-response analysis. On the other hand, the
findings of decreased peripheral nerve function are supported by parallel measures in several
rodent studies.
Uncertainties in the acute and chronic hazard values stem from the following sources:
Non-cancer hazard values (e.g., NOAELs, LOAELs, BMD): PODs were identified from the
animal studies that were suitable for dose-response analysis. The process of identifying PODs for
various health effects domains involved the evaluation of the strengths and limitations of the data
and the weight of the scientific evidence for a particular health effects domain before supporting an
association between 1-BP exposure and various human health effects. The selected PODs values
(e.g., NOAEL, LOAEL or BMD) depend on the current available data and could change as
additional studies are published.
Also, when selecting a BMD as a POD, the selection of the benchmark dose response (BMR) (e.g.,
1%, 5% or 10% level) directly affects the calculation of the BMD. There are uncertainties related to
Page 296 of 486
-------
the BMRs since their selection depends on scientific judgments on the statistical and biological
characteristics of the dataset and how the BMDs will be finally used.
In addition, there are uncertainties about the appropriate dose-response model used to generate the
BMDs. However, these uncertainties should be minimal if the chosen model fits well the
observable range of the data, as discussed in EPA Benchmark Dose Technical Guidance.
• Duration adjustment to continuous exposure: Most of the PODs used to derive HECs
came from studies that did not expose animals or humans to 1-BP on a continuous basis.
These PODs were then mathematically adjusted to reflect equivalent continuous exposures
(daily doses) over the study exposure period under the assumption that the effects are related
to concentration x time (C x t), independent of the daily (or weekly) exposure regimen (U.S.
EPA. 201 1).However, the validity of this assumption is generally unknown, and, if there are
dose-rate effects, the assumption of C x t equivalence would tend to bias the POD
downwards (U.S. EPA. 2011). A single exposure to 1-BP at a critical window of fetal
development was assumed to produce adverse developmental effects. This is a health
protective approach and no duration adjustment was performed for adverse developmental
outcomes.
• Extrapolation of repeated dose developmental effects to acute scenarios: EPA considers
developmental toxicity endpoints to be applicable to acute exposures. While there is some
uncertainty surrounding this consideration because the precise critical exposure window is
unknown, multiple publications suggest that developmental effects (e.g., decreased live litter
size and increased post-implantation loss) may result from a single exposure during a critical
window of development. There are uncertainties related to whether developmental effects
observed in developmental toxicity studies may result from a single exposure to 1-BP. In this
evaluation, the risk assessment associated with acute exposure used the hazard value for
decreases in litter size and increases in post-implantation loss from the (WTL Research. 2001)
two-generation reproductive toxicity study. This is considered a health protective approach.
For cancer hazard assessment, the major uncertainty is whether the mechanism/mode of action of
1-BP carcinogenesis should be considered mutagenic. The uncertainty arises because the results of
genotoxicity testing have been mixed, as described in detail in Section 3.2.5.6 above. While a
MMOA may be operative at least in part for the carcinogenicity of 1-BP, the default linear
extrapolation method for dose-response is used. For the cancer dose-response assessment,
uncertainties exist arising from the animal to human extrapolation in the derivation of the IUR. A
source of uncertainty is the cancer model used to estimate the POD for the IUR derivation. The
POD was based on a model averaging approach to fit the bioassay data for lung tumors. Although
the model average fit the data, alternate model selections can also fit the data. A sensitivity analysis
comparing reasonable alternate model choices found similar PODs therefore, the impact of
selecting between alternative models results in similar IURs.
Page 297 of 486
-------
Data gaps include conclusive information on the mutagenic properties of 1-BP and its metabolites
in vitro and in vivo, data on the nature and frequencies of mutations in workers exposed to 1-BP
over time, information on variations in susceptibility of the human population to cancer (e.g.,
related to CYP2E1 polymorphisms or other differences), and associations between developmental
life stage exposure and cancer in childhood and adulthood. The available data are not sufficient to
establish the molecular initiating and/or key events in the adverse outcome pathway from 1-BP
exposure to development of cancer.
4,3,4 Uncertainties in the Risk Assessment
4.3.4.1 Environmental Risk Characterization
While EPA has determined that sufficient data are available to characterize the overall
environmental hazards of 1-BP under the conditions of use of this evaluation, there are
uncertainties regarding the available environmental hazard data for 1-BP. As discussed in Section
3.1.2, the single acute study identified for 1-BP was part of a larger EPA-funded effort to generate
an acute toxicity database for a variety of organic chemicals (Geiger et al.. 1988). As such, this
study was subject to the editing, quality assurance, and peer review procedures set forth by the
EPA for grant-funded projects. This study was reviewed by EPA for data quality, where it was
found to be of high quality. The systematic review of this study is available in the Systematic
Review Supplemental File: Data Quality Evaluation of Ecological Hazard Studies. (EPA. 2019k).
Many of the data quality evaluation metrics used in this evaluation are similar to the peer review
procedures used to understand the quality of published scientific articles. The confidence in the
available data to characterize the environmental hazards of 1-BP is bolstered by the use of the
QSAR modeling program ECOSAR (v2.0) (EPA. 2017) lending greater confidence to the risk
estimates. The strength of the evidence for the multiple lines of evidence is medium based on high
quality empirical data for fish and modeling data from analogues that provide support for multiple
taxa including fish.
The ECOSAR modeling program used the most robust and data rich chemical class, neutral
organics, to predict the environmental hazards to fish, aquatic invertebrates, and algae from acute
and chronic exposure to 1-BP. This substantially broadens the available data that can be used to
validate the use of the single acute fish toxicity study to characterize the environmental hazards
and risks of 1 -BP. As explained in Section 3.1.4, the extensive dataset used to populate the neutral
organics chemical class includes several chemicals that are similar to 1-BP in terms of molecular
weight and logKow. In addition, much of the data used to populate the ECOSAR training set was
comprised of data generated as part of the same research effort as the single acute fish toxicity
study (Geiger et al.. 1988). The acute fish toxicity data and the predicted toxicity values from
ECOSAR are consistent in that both indicate that 1-BP presents a moderate environmental hazard
(see section 3.1.6 for a comparison of the available ecotoxicity data with ECOSAR modeling
outputs).
No chronic toxicity studies were identified that directly assess the chronic duration effects of 1-BP
to the environment. As a result, hazard to aquatic species resulting from chronic exposure was
Page 298 of 486
-------
estimated by applying an acute-to-chronic ratio to acute hazard data as well as ECOSAR modeling.
As these values are estimates of chronic hazard, there are uncertainties regarding the use of these
values to estimate the environmental risks from chronic exposure to 1-BP. Both the use of an acute
to chronic ratio and ECOSAR modeling are commonly utilized techniques to estimate potential
hazards to environmental receptors from chronic exposures and represent the best available data
for 1-BP. Frequency and duration of exposure also affects potential for adverse effects in aquatic
organisms, especially for chronic exposures. In the case of 1-BP, the number of days that a COC
was exceeded was not calculated using E-FAST, but instead the maximum expected surface water
concentration from an acute exposure, representing a high-end estimate of exposure interval or
pulse exposure, was compared to the estimated chronic concentrations of concern. This
conservative screening-level approach is expected to be protective of longer-term chronic
exposures which are generally lower than acute-duration exposures. As described in Section 4.1,
this assessment presents a screening-level assessment of relevant routes of exposure, which in the
case of 1-BP are the aquatic exposure pathways, evaluate ecological exposures in the US that may
be associated with releases of 1-BP to surface waters. This assessment was intended as a first-tier,
or screening-level, evaluation. Discharging or releasing facilities were chosen from EPA's TRI.
EPA did not quantitatively assess potential risks to terrestrial receptors and sediment-dwelling
organisms. Instead, a considerations of the physical-chemical and environmental fate
characteristics of the chemical led EPA to determine that the potential exposures to organisms in
these compartments are expected to be low and risks are not expected. As discussed above in
Section 3.1, as well as in the Problem Formulation (U.S. EPA. 2018c). this assumption was based
on the high volatility (Henry's Law constant of 7.3X10"3 atm-m3/mole), high water solubility (2.4
g/L), and low log Koc (1.6) which suggests that 1-BP will only be present at low concentrations in
the sediment and terrestrial environmental compartments. Although the conclusion of of a low
potential for exposure to sediment-dwelling organisms is not verified with monitoring data or
hazard data specifically conducted with sediment-dwelling organisms, the available physical
chemical property data for 1-BP provide sufficient evidence to determine that these exposures are
not significant enough to be biologically relevant.
The foundation of the ecological risk assessment process is the relationship between the amount of a
substance a receptor is exposed to and the potential for adverse effects resulting from the exposure.
This established dose-response relationship provides the ability to quantitatively evaluate the potential
environmental impacts that may result from a given exposure scenario. Because of uncertainties
inherent in deriving RQs, values are protective so that the risk estimate can state with a high degree of
confidence that RQ values < 1 are not an ecological risk and can be screened out from further analysis.
The environmental risk evaluation used reasonably available environmental hazard, exposure, fate,
and chemistry data, but was still a screening-level evaluation due to the limited amount of hazard
and exposure information.
The environmental risk assessment for 1-BP applied two assessment factors to the reasonably
available environmental hazard data for aquatic species in order to perform a screening-level
analysis of potential environmental risks under the conditions of use within the scope of this risk
Page 299 of 486
-------
evaluation. Assessment factors (AFs) were used to calculate the acute and chronic COCs for 1-BP.
As described in Section 3.1.1, 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 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.
The first AF, an acute-to-chronic ratio (ACR) extrapolation, is utilized to estimate the hazards of
chronic exposure to 1-BP in the absence of empirical data. As data characterizing the
environmental hazards of chronic exposure to 1-BP are not available, an ACR value of 10 is used
to extrapolate these hazard values from acute toxicity endpoints for aquatic species. Utilizing a
single value of 10 to extrapolate from acute to chronic hazard for species in the aquatic
compartment is consistent with existing EPA methodology for the screening and analysis of
industrial chemicals (U.S. EPA. 2012e). While this value is routinely utilized by EPA to assess the
hazard of new industrial chemicals, there is uncertainty with regard to using a single ACR value to
estimate chronic hazards across species and chemicals. Available information in the literature that
indicates the use of an ACR value between 10 may not be protective across all chemicals, species,
trophic levels, and modes of action. For example, Kenaga (1982) indicates that acute to chronic
ratios can vary by as much as 1-18,000. Using an ACR of 10 is representative of the median ACR
for chemicals that exhibit non-polar narcosis39 (Ahlers et al.. 2006; Chapman et al.. 1998; Kenaga.
1982; Giesv and Granev. 1989). For example, Ahlers et.al., (2006) analyzed available ecotoxicity
data for 240 chemicals and determined that the median (50th percentile) ACR is 10.5 for fish, 7.0
for Daphnia magna, and 5.4 for green algae. While the authors concluded that an ACR of 10 is not
protective across all chemicals and trophic levels, these findings add a line of evidence in support
of utilizing an ACR of 10 to estimate chronic hazard from exposure of 1-BP (Ahlers et al.. 2006).
Elsewhere, a median ACR of 12 was determined for fish and 8.8 for Daphnia magna, resulting in a
median ACR for both species of 9.9 (May et al.. 2016). Additionally, variation in ACR is reported
based on the mode of action of the chemical. A comparison of 240 chemicals found that >50% of
non-polar narcotic chemicals exhibit an ACR below 10 for aquatic species (Kienzler et al.. 2017).
Additionally, May et al., (2016) reported a median ACR of 7.6 for non-polar narcotic chemicals,
with a 90th percentile ACR value of 24.1. While there is uncertainty about the degree of protection
afforded by the use of an ACR of 10 for fish and Daphnia, the above evidence as well as the
ECOSAR-predicted toxicity values for acute and chronic exposure to 1-BP, as shown in Table 3-1,
provide lines of evidence to indicate that an ACR of 10 is protective for 1-BP. Furthermore, given
the limited potential for chronic-duration aquatic exposures as a result of the high volatility and
low persistence of 1-BP in the environment, chronic exposure of 1-BP to aquatic species is
expected to be limited. Finally, to account for any additional sources of variability not accounted
for in the ACR extrapolation, a second assessment factor of 10 is applied to the estimate hazard
value for chronic exposure as discussed below.
39 OECD QSAR Toolbox version 4.3.(Accessed November, 2019; https://qsartoolbox.org/)
Page 300 of 486
-------
A second AF is applied to the acute and chronic hazard endpoints for aquatic species to calculate a
Concentration of Concern (COC) for use in the screening-level analysis of environmental hazards
to account for differences in inter- and intra-species variability, as well as laboratory-to-field
variability. For fish and aquatic invertebrates (e.g., Daphnia), the acute COC values are calculated
by dividing the most sensitive endpoint by an AF of 5. For chronic COCs, and to calculate a COC
for algae, where multiple generations can be present over the course of a standard toxicity test, an
AF of 10 is used. Similarly to the use of an acute to chronic ratio, the use of this assessment factor
is consistent with EPA methodology for the screening and assessment of industrial chemicals
(Suter. 2016s) (U.S. EPA. 2012e) (U.S. EPA, 2013b).
4.3.4.2 Human Health Characterization
The non-cancer acute or chronic evaluations were expressed in terms of MOEs. MOEs are obtained
by comparing the hazard values (i.e., HEC) for various 1-BP-related health effects with the
exposure concentrations for the specific use scenarios. Given that the MOE is the ratio of the
hazard value divided by the exposure, the confidence in the MOEs is directly dependent on the
uncertainties in the hazard/dose-response and exposure assessments that supported the hazard and
exposure estimates used in the MOE calculations.
Overall uncertainties in the exposure estimates used in the MOE calculations include uncertainties
in the exposure monitoring and modeling. In the occupational exposure monitoring data for
workers, the sites used to collect 1-BP were not selected randomly; therefore, the reported data
may not be representative of all occupational exposure scenarios. The exposure modeling
approaches used for both occupational and consumer scenarios employed knowledge-based
assumptions that may not apply to all occupational- and consumer-use scenarios.
The human populations quantitatively evaluated in this risk evaluation include individuals of both
sexes (>16 and older, including pregnant females) for occupational and consumer settings.
Although exposures to younger non-users may be possible, the margins of exposure calculated for
women and men of reproductive age are expected to be protective of this sensitive subpopulation.
Currently there are insufficient data regarding specific genetic and/or lifestage differences that
could impact 1-BP metabolism and toxicity for further refinement of the risk assessment.
The chronic exposures leading to risk for the occupational scenarios assumed that the non-cancer
human health effects are constant for a working lifetime based on the exposure assumptions used in
the occupational exposure assessment. However, the risks could be under- or over-estimated
depending on the variations to the exposure profile of the workers and occupational non-users using
1-BP-containing adhesives, dry cleaning and spot cleaners, vapor degreasing, cold cleaning, and
aerosol degreasers.
Confidence in the PBPK model predictions for 1-BP concentrations in blood and tissues are limited
by the lack of comparison of model predictions with measured data. The PBPK model was further
extended to simulate human exposures by scaling the physiological parameters to humans,
Page 301 of 486
-------
assuming the partition coefficients are the same in rats and humans and scaling metabolic
parameters by BW3/4. Cross species and route to route extrapolations with the Garner et al. (2015)
model are precluded by the lack of data to inform a model of a species other than rat and a route
other than inhalation.
Limited toxicological data is available by the oral route, and no repeated-dose toxicity studies by
the dermal route were identified on 1-BP. However, although the toxicological data via the oral
route is insufficient for quantitative dose-response assessment, data from these studies were used
for qualitative support in the weight of the scientific evidence for nervous system effects (see
Section 3.2.5.5 and Appendix J), suggesting that, at least for the nervous system endpoint, the
delivery of 1-BP via the inhalation- {i.e., pulmonary/systemic circulation) and oral- (i.e., portal
circulation) routes of exposure results in comparable toxic endpoints.
EPA chose to derive dermal HEDs for dermal exposures by extrapolating from other routes for
systemic endpoints {i.e., not point of contact effects) and none of the key endpoints for 1-BP (liver,
kidney, reproductive, developmental and nervous system effects) were considered point of contact
therefore all were used for route-to-route extrapolation. The route-to-route extrapolations enabled
EPA to estimate applied dermal PODs. Since physiologically based pharmacokinetic/
pharmacodynamic (PBPK/PD) models that would facilitate route-to-route extrapolation have not
been identified, there is no relevant kinetic or metabolic information for 1-BP that would facilitate
development of dosimetric comparisons. The studies by the oral route were insufficient for
quantitative dose-response assessment; therefore, EPA chose to derive dermal HEDs for dermal
exposures by extrapolating from the inhalation PODs. However, the inhalation studies were
performed by whole body exposure, rather than nose only exposure, which may have led to
additional dosing by the oral and dermal routes of exposure, due to deposition on fur and the
grooming behavior of rodents, resulting in uncertainty of actual dose received. EPA was unable to
conclude with certainty that comparable toxic endpoints would be associated with the dermal route
of exposure, considering the expected quantitative ADME differences and the absence of an
adequate PBPK model. Notwithstanding these uncertainties, EPA considered this approach
appropriate considering the comparable toxic endpoints identified in the available repeated-dose
oral/inhalation toxicity studies and the uncertainty with the putative toxicant {i.e., 1-BP or a
metabolite(s)).
As discussed previously, the estimates for extra cancer risk were based on the assumption of
linearity in the relationship between 1-BP exposure and probability of cancer at low doses, in the
absence of sufficient information on mode of action.
4.4 Other Risk Related Considerations
4.4.1 Potentially Exposed or Susceptible Subpopulations
TSCA 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
Page 302 of 486
-------
subpopulation (PESS) 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 infants, children, pregnant women, workers, or the elderly."
In developing the exposure assessment for 1-BP, EPA analyzed reasonably available information
to ascertain whether some human receptor groups may have greater exposure or susceptibility than
the general population to the hazard posed by 1-BP. Exposures of 1-BP would be expected to be
higher amongst groups with 1-BP containing products in their homes, and workers who use 1-BP
as part of typical processes.
EPA identified potentially exposed or susceptible subpopulations for further analysis during the
development and refinement of the life cycle, conceptual models, exposure scenarios, and analysis
plan. In Section 2.3.1, EPA addressed the potentially exposed or susceptible subpopulations
identified as relevant based on greater exposure in occupational settings. In Section 2.3.2, EPA
addressed the potentially exposed or susceptible subpopulations for consumer users between the
ages of 11-21 as well as adults. EPA also addressed potentially exposed or susceptible
subpopulations for bystanders within residences where a consumer product containing 1-BP may
be used. Bystanders, for purposes of this risk evaluation, can be any age group (infant to elderly).
Of the human receptors identified in the previous sections, EPA identifies the following as
potentially exposed or susceptible subpopulations due to their greater exposure and considered
them in the risk evaluation:
• Workers and occupational non-users. EPA assessed exposure to these subpopulations using a
combination of personal exposure monitoring data (measured data) and modeling approaches.
The exposure estimates were applicable to both male and female workers of reproductive age,
including adolescents. Section 2.4 provides more details on these subpopulations across various
industry sectors that are likely to use 1-BP.
• Consumer users and bystanders associated with consumer use. 1-BP has been identified as
being present in products available to consumers for purchase and use; however, only some
individuals within the general population are expected to use these products. Therefore, those
who do use these products are a potentially exposed or susceptible subpopulation due to greater
exposure. Consumer bystanders, although they do not use a product containing 1-BP, are also a
potentially exposed or susceptible subpopulation due to the possibility that bystanders can be
any age group (including infants, toddlers, children, and elderly) with greater exposure when in
a residence where products containing 1-BP are used. A description of the exposure assessment
for consumers is available in Section 2.3.2.
Page 303 of 486
-------
There are some exposure scenarios where greater exposure from multiple sources may occur and
individuals who may have greater potential for exposure to 1-BP. For example, some workers and
occupational non-users may also use consumer products containing 1-BP, and have additional
exposure outside of the workplace. EPA also investigated the effects of 1-BP on susceptible
lifestages and subpopulations. Consideration of other lifestages, such as male and non-pregnant
female workers in the occupational environment, children in the home environment would require
using an alternative POD based on systemic toxicity, instead of using the POD based on
developmental toxicity. Other endpoints associated with systemic toxicity generally had higher
human equivalent concentrations than those associated with developmental toxicity. Therefore
EPA assumed that margins of exposure for pregnant women would also be protective of other
lifestages.
While it is anticipated that there may be differential 1-BP metabolism based on lifestage; currently
there are no data available, therefore the impact of this cannot be quantified. Similarly, while it is
known that there may be genetic differences that influence CYP2E1 metabolic capacity, there may
also be other metabolizing enzymes that are functional and impact vulnerability. There is
insufficient data to quantify these differences for risk assessment purposes.
Heterogeneity among humans is an uncertainty associated with extrapolating the derived PODs to
a diverse human population. One component of human variability is toxicokinetic, such as
variations in CYP2E1 and glutathione transferase activity in humans (Arakawa et al.. 2012;
Trafalis et al.. 2010) which are involved in 1-BP metabolism in humans. EPA did not have
chemical-specific information on susceptible subpopulations, or the distribution of susceptibility in
the general population that could be used to decrease or increase the default intraspecies UFh for
toxicodynamic variability of 3. As such, EPA used an intraspecies UFh of 10 for the risk
assessment.
EPA was unable to directly account for all possible PESS considerations and subpopulations in the
risk estimates. It is unknown whether the lOx UF to account for human variability will cover the
full breadth of human responses, and subpopulations with particular disease states or genetic
predispositions may fall outside of the range covered by this UF. As previously discussed, EPA
also only considered acute effects for all consumer COUs evaluated except for the insulation (off-
gassing) COU as described in Section 2.3.2.1. While typical use patterns are unlikely to result in
any chronic effects for the vast majority of consumers, EPA cannot rule out that consumers at very
high frequencies of use may be at risk for chronic hazards, especially if those consumers also
exhibit biological susceptibilities. EPA can also not rule out that certain subpopulations, whether
due to very elevated exposure or biological susceptibility, may be at risk for hazards that were not
fully supported by the weight of the scientific evidence or could not be quantified (e.g., immune
and blood effects). However, in these circumstances EPA assumes that these effects are likely to
occur at a higher dose than more sensitive endpoints that were accounted for by risk estimates.
Page 304 of 486
-------
4.4,2 Aggregate and Sentinel Exposures
Section 2605(b)(4)(F)(ii) of TSCA requires 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. 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 this risk evaluation, EPA determined that aggregating dermal and inhalation
exposure for risk characterization was not appropriate due to uncertainties in quantifying the
relative contribution of dermal vs inhalation exposure, since dermally applied dose could evaporate
and then be inhaled. Aggregating exposures from multiple routes could therefore inappropriately
overestimate total exposure, as simply adding exposures from different routes without an available
PBPK model for those routes would compound uncertainties. Without a PBPK model to account
for toxicokinetic processes, the true internal dose for any given exposure cannot be determined.
Conversely, not aggregating exposures may underestimate total exposure for a given individual.
EPA also did not consider aggregate exposure among individuals who may be exposed both in an
occupational and consumer context because there is insufficient information reasonably available
as to the likelihood of this scenario or the relative distribution of exposures from each pathway.
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." In terms of this risk evaluation, EPA considered sentinel exposures by
considering exposures to populations who may have upper bound exposures - for example,
workers who perform activities with higher exposure potential, or consumers who have higher
exposure potential (e.g., those involved with do-it-yourself projects) or certain physical factors like
body weight or skin surface area exposed. EPA characterized high-end exposures in evaluating
exposure using both monitoring data and modeling approaches. Where statistical data are available,
EPA typically uses the 95th percentile value of the available dataset to characterize high-end
exposure for a given condition of use. For consumer and bystander exposures, EPA characterized
sentinel exposure through a "high-intensity use" category based on both product and user-specific
factors.
4.5 Risk Conclusions
4.5.1 Environmental Risk Conclusions
Based on a consideration of the physical chemical properties and uses of 1-BP, exposure to aquatic
species is the only route of exposure to the environment that was quantitatively assessed in this risk
evaluation. Risks to terrestrial and sediment-dwelling aquatic species were qualitatively evaluated
by considering physical-chemical and environmental fate properties, which indicate that there is a
low potential for exposure to terrestrial and sediment-dwelling aquatic species. The conclusions for
these pathways were not updated since the preliminary assessment presented in the Problem
Formulation and Draft Risk Evaluation. The quantitative assessment of water column-dwelling
aquatic species was updated in this final risk evaluation to incorporate ECOSAR modeling results
for environmental hazards to reduce uncertainty about the limited environmental hazard data
Page 305 of 486
-------
available for 1-BP. EPA conducted a screening-level assessment of the available environmental
hazards and release information to calculate RQs to quantify potential risks to the environment
from 1-BP. As previously stated, an RQ below 1 indicates that the exposure concentrations of 1-BP
is less than the concentrations that would cause an effect to organisms in the aquatic pathways. The
RQ values for risks from acute and chronic exposure to 1-BP are <1, based on a comparison of all
available data characterizing exposure and hazard to aquatic species. These values indicate that
risks to the environment are not identified based on the conditions of use within the scope of this
risk evaluation.
4.5.2 Human Health Risk Conclusions
4.5.2.1 Summary of Risk Estimates for Workers and ONUs
Table 4-58 summarizes the risk estimates for inhalation and dermal exposures for all occupational
exposure scenarios. Risk estimates that exceed the benchmark {i.e., MOE less than the benchmark
MOE or cancer risks greater than the benchmark cancer risk) are highlighted by shading the cell.
When both monitoring and modeling inhalation exposures are available, EPA presented the more
conservative estimate in the table. The occupational exposure assessment and risk characterization
are described in more detail in Sections 2.3.1 and 4.2.3, respectively.
The risk summary below is based on the POD selected from among the most sensitive acute and
chronic non-cancer endpoints, as well as cancer. EPA selected developmental effects based on
NLogistic modeling as the most sensitive acute and chronic non-cancer endpoints. Risk estimates
are also presented considering PPE up to respirator APF 50 and glove PF 10 or 20. For each
exposure scenario, the lowest protection factor that results in no indication of risks is shown {i.e., if
estimated risks do not exceed the benchmark for APF 10 and above, the risk estimate for APF 10
only is shown).
Inhalation Exposure
For acute and chronic exposures via inhalation without PPE {i.e., no respirators), there are non-
cancer and cancer risks for workers relative to the benchmark for most conditions of use at the
high-end exposure level. For batch vapor degreasing (open-top), cold cleaning, and spray adhesive
conditions of use, risks were present at the high-end exposure level even when respirators (up to
APF 50) are worn.
While ONUs are assumed to have lower exposure levels than workers, there are also non-cancer
and cancer risks following acute and chronic exposures at the high-end exposure level for many
conditions of use. ONUs are assumed to not wear respirators.
Dermal Exposure
For acute and chronic exposures via dermal contact without PPE {i.e., no gloves), risks are not
indicated for workers for non-cancer effects at both central tendency and high-end exposure levels
across all conditions of use (ONUs are assumed to not have direct dermal contact with 1-BP).
Page 306 of 486
-------
Risks are indicated for cancer effects at the high-end exposure level across all conditions of use,
except when gloves with a protection factor of at least 5 are worn.
Page 307 of 486
-------
Table 4-58. Occupational Risk Summary Table
Life Cycle
Stage /
Category
Subcategory
Occupational
Exposure
Scenario
Population
Exposure
Route
and
Duration
Exposure
Est.
Method
Exposure
Level
Risk Estimates for No PPE
Risk Estimates with PPE
Acute Non-
cancer
(benchmark
MOE =100)
Chronic
Non-
cancer
(benchmark
MOE =100)
Cancer
(benchmark
= 10"4)
Acute Non-
cancer
(benchmark
MOE =100)
Chronic
Non-
cancer
(benchmark
MOE =100)
Cancer
(benchmark
= 10"4)
Manufacture
- Domestic
manufacture
Domestic
manufacture
Manufacture
(see Section
2.3.1.5)1
Worker
Inhalation
Monitoring
data
Central
Tendency
189
265
1.4E-04
1,889
(APF 10)
2,652
(APF 10)
1.4E-05
(APF 10)
High-end
63
88
5.5E-04
630
(APF 10)
884
(APF 10)
5.5E-05
(APF 10)
Dermal
Model
Central
Tendency
405
569
6.5E-05
-
-
-
High-end
135
190
2.5E-04
-
-
5.0E-05
(PF5)
Manufacture
- Import
Import
Import (see
Section2.3.1.6)
2
Worker
Inhalation
Model
Central
Tendency
4,441
6,235
6.1E-06
-
-
-
High-end
300
421
1.2E-04
-
-
1.2E-05
(APF 10)
Dermal
Model
Central
Tendency
405
569
6.5E-05
-
-
-
High-end
135
190
2.5E-04
-
-
5.0E-05
(PF5)
Processing -
Processing
as a reactant
Intermediate in
various chem
and pdt mfg,
Processing as a
Reactant (see
Section2.3.1.7)
2
Worker
Inhalation
Model
Central
Tendency
4,441
6,235
6.1E-06
-
-
-
High-end
300
421
1.2E-04
-
-
1.2E-05
(APF 10)
Dermal
Model
Central
Tendency
405
569
6.5E-05
-
-
-
High-end
135
190
2.5E-04
-
-
5.0E-05
(PF5)
Page 308 of 486
-------
Life Cycle
Stage /
Category
Subcategory
Occupational
Exposure
Scenario
Population
Exposure
Route
and
Duration
Exposure
Est.
Method
Exposure
Level
Risk Estimates for No PPE
Risk Estimates with PPE
Acute Non-
cancer
(benchmark
MOE =100)
Chronic
Non-
cancer
(benchmark
MOE =100)
Cancer
(benchmark
= 10"4)
Acute Non-
cancer
(benchmark
MOE =100)
Chronic
Non-
cancer
(benchmark
MOE =100)
Cancer
(benchmark
= 10"4)
Processing -
Incorp. into
formulation,
mixture or
reaction
product
Solvents for
cleaning or
degreasing
Processing -
Incorporating
into formulation,
mixture or
reaction product
(see Section
2.3.1.8)
Worker
Inhalation
Monitoring
Data
Central
Tendency
2
3
1.1E-02
118
(APF 50)
166
(APF 50)
2.3E-04
(APF 50)
High-end
Dermal
Model
Central
Tendency
405
569
6.5E-05
-
-
-
High-end
135
190
2.5E-04
-
-
5.0E-05
(PF5)
ONU
Inhalation
Monitoring
Data
Central
Tendency
110
154
2.5E-04
N/A
N/A
N/A
High-end
62
87
5.7E-04
N/A
N/A
N/A
Processing -
Incorp. into
articles
Solvents (which
become part of
product
formulation or
mixture) in
construction
Processing -
Incorporation
into Articles
(see Section
2.3.1.9)2
Worker
Inhalation
Model
Central
Tendency
4,441
6,235
6.1E-06
-
-
-
High-end
300
421
1.2E-04
-
-
1.2E-05
(APF 10)
Dermal
Model
Central
Tendency
405
569
6.5E-05
-
-
-
High-end
135
190
2.5E-04
-
-
5.0E-05
(PF5)
Processing -
Repackaging
Solvent for
cleaning or
degreasing in all
other basic
organic chemical
manufacturing
Repackaging
(see Section
2.3.1.10)2
Worker
Inhalation
Model
Central
Tendency
4,441
6,235
6.1E-06
-
-
-
High-end
300
421
1.2E-04
-
-
1.2E-05
(APF 10)
Dermal
Model
Central
Tendency
405
569
6.5E-05
-
-
-
High-end
135
190
2.5E-04
-
-
5.0E-05
(PF5)
Page 309 of 486
-------
Risk Estimates for No PPE
Risk Estimates with PPE
Life Cycle
Stage /
Category
Occupational
Exposure
Scenario
Exposure
Exposure
Est.
Method
Subcategory
Population
Route
and
Duration
Exposure
Level
Acute Non-
cancer
(benchmark
MOE =100)
Chronic
Non-
cancer
(benchmark
MOE =100)
Cancer
(benchmark
= 10"4)
Acute Non-
cancer
(benchmark
MOE =100)
Chronic
Non-
cancer
(benchmark
MOE =100)
Cancer
(benchmark
= 10"4)
Inhalation
Model
Central
Tendency
4,441
6,235
6.1E-06
-
-
-
Processing -
Recycling
Disposal,
Recycling (see
Worker
High-end
300
421
1.2E-04
-
-
1.2E-05
(APF 10)
Recycling
Section
2.3.1.21 )2
Dermal
Model
Central
Tendency
405
569
6.5E-05
-
-
High-end
135
190
2.5E-04
-
-
5.0E-05
(PF5)
Distribution
in commerce
Distribution
Not assessed as a separate operation; exposures/releases from distribution are considered within each condition of use.
Inhalation
Monitoring
Central
Tendency
3
4
1.1E-02
127
(APF 50)
178
(APF 50)
2.1E-04
(APF 50)
Batch Vapor
Worker
Data
High-end
0.34
0.48
1.0E-01
17
(APF 50)
24
(APF 50)
2.0E-03
(APF 50)
Degreaser
(Open-Top)
Dermal
Model
Central
Tendency
418
586
6.3E-05
-
-
-
(see Section
2.3.1.11)
High-end
139
195
2.4E-04
-
-
4.9E-05
(PF5)
Industrial /
commercial
Batch vapor
ONU
Inhalation
Monitoring
Data
Central
Tendency
170
239
1.6E-04
N/A
N/A
N/A
use - Solvent
(for cleaning
or
degreasing)
degreaser (e.g.,
open-top,
closed-loop)
High-end
37
52
9.4E-04
N/A
N/A
N/A
Inhalation
Model
Central
Tendency
450
631
5.6E-05
4,496
(APF 10)
6,312
(APF 10)
5.6E-06
(APF 10)
Batch Vapor
Degreaser
(Closed-Loop)
(see Section
2.3.1.12)
Worker
High-end
36
50
7.4E-04
355
(APF 10)
499
(APF 10)
7.4E-05
(APF 10)
Dermal
Model
Central
Tendency
418
586
6.3E-05
-
-
-
High-end
139
195
2.4E-04
-
-
4.9E-05
(PF5)
ONU
Inhalation
Model
Central
Tendency
856
1,201
3.0E-05
N/A
N/A
N/A
Page 310 of 486
-------
Risk Estimates for No PPE
Risk Estimates with PPE
Life Cycle
Stage /
Category
Occupational
Exposure
Scenario
Exposure
Exposure
Est.
Method
Subcategory
Population
Route
and
Duration
Exposure
Level
Acute Non-
cancer
(benchmark
MOE =100)
Chronic
Non-
cancer
(benchmark
MOE =100)
Cancer
(benchmark
= 10"4)
Acute Non-
cancer
(benchmark
MOE =100)
Chronic
Non-
cancer
(benchmark
MOE =100)
Cancer
(benchmark
= 10"4)
High-end
63
88
4.2E-04
N/A
N/A
N/A
In-line vapor
degreaser (e.g.,
conveyorized,
web cleaner)
In-line Vapor
Degreaser
(see Section
2.3.1.13)
See exposure estimates for Batch Vapor Degreaser (Open-Top)
Inhalation
Monitoring
Central
Tendency
4
6
6.8E-03
198
(APF 50)
278
(APF 50)
1.4E-04
(APF 50)
Worker
Data
High-end
2
3
1.5E-02
115
(APF 50)
161
(APF 50)
3.0E-04
(APF 50)
Cold Cleaner
Cold Cleaner
(see Section
Dermal
Model
Central
Tendency
418
586
6.3E-05
-
-
-
2.3.1.14)
High-end
139
195
2.4E-04
-
-
4.9E-05
(PF5)
ONU
Inhalation
Monitoring
Data
Central
Tendency
7
9
4.1E-03
N/A
N/A
N/A
High-end
N/A
N/A
N/A
Inhalation
Model
Central
Tendency
3
4
9.5E-03
N/A
N/A
N/A
Aerosol Spray
Degreaser/
Cleaner (see
Section
2.3.1.15)
High-end
1
1
3.6E-02
N/A
N/A
N/A
Aerosol spray
degreaser/
cleaner
Worker
Dermal
Model
Central
Tendency
405
569
6.5E-05
-
-
-
High-end
135
190
2.5E-04
-
-
5.0E-05
(PF5)
ONU
Inhalation
Model
Central
Tendency
155
217
1.6E-04
N/A
N/A
N/A
High-end
18
26
1.4E-03
N/A
N/A
N/A
Page 311 of 486
-------
Life Cycle
Stage /
Category
Subcategory
Occupational
Exposure
Scenario
Population
Exposure
Route
and
Duration
Exposure
Est.
Method
Exposure
Level
Risk Estimates for No PPE
Risk Estimates with PPE
Acute Non-
cancer
(benchmark
MOE =100)
Chronic
Non-
cancer
(benchmark
MOE =100)
Cancer
(benchmark
= 10"4)
Acute Non-
cancer
(benchmark
MOE =100)
Chronic
Non-
cancer
(benchmark
MOE =100)
Cancer
(benchmark
= 10"4)
Industrial /
commercial
use -
Adhesives
and sealants
Adhesive
chemicals -
spray adhesive
for foam cushion
manufacturing
and other uses
Adhesive
Chemicals
(Spray
Adhesives)
(see Section
2.3.1.18)
Sprayer
Inhalation
Monitoring
Data (Post-
EC)
Central
Tendency
1
1
2.8E-02
48
(APF 50)
67
(APF 50)
5.7E-04
(APF 50)
High-end
0.41
1
8.6E-02
20
(APF 50)
28
(APF 50)
1.7E-03
(APF 50)
Dermal
Model
Central
Tendency
506
711
5.2E-05
-
-
-
High-end
169
237
2.0E-04
-
-
4.0E-05
(PF5)
Non-
Sprayer
Inhalation
Monitoring
Data (Post-
EC)
Central
Tendency
0.94
1
2.9E-02
47
(APF 50)
66
(APF 50)
5.7E-04
(APF 50)
High-end
0.59
1
5.9E-02
29
(APF 50)
41
(APF 50)
1.2E-03
(APF 50)
ONU
Inhalation
Monitoring
Data (Post-
EC)
Central
Tendency
9
12
3.2E-03
N/A
N/A
N/A
High-end
3
4
1.1E-02
N/A
N/A
N/A
Industrial /
commercial
use -
Cleaning and
furniture
care
products
Dry cleaning
solvent
Dry Cleaning
(see Section
2.3.1.16)
Worker
Inhalation
Monitoring
Data
Central
Tendency
0.58
0.82
4.7E-02
N/A
N/A
N/A
High-end
0.34
0.42
1.0E-01
N/A
N/A
N/A
Dermal
Model
Central
Tendency
431
605
6.1E-05
N/A
N/A
N/A
High-end
144
202
2.4E-04
N/A
N/A
N/A
ONU
Inhalation
Monitoring
Data
Central
Tendency
1
2
1.9E-02
N/A
N/A
N/A
High-end
1
1
4.2E-02
N/A
N/A
N/A
Spot cleaner,
stain remover
Spot Cleaner,
Stain Remover
(see Section
2.3.1.17)
Worker
Inhalation
Model
Central
Tendency
5
31
1.2E-03
N/A
N/A
N/A
High-end
2
14
2.7E-03
N/A
N/A
N/A
Dermal
Model
Central
Tendency
431
605
6.1E-05
N/A
N/A
N/A
High-end
144
202
2.4E-04
N/A
N/A
N/A
Page 312 of 486
-------
Life Cycle
Stage /
Category
Subcategory
Occupational
Exposure
Scenario
Population
Exposure
Route
and
Duration
Exposure
Est.
Method
Exposure
Level
Risk Estimates for No PPE
Risk Estimates with PPE
Acute Non-
cancer
(benchmark
MOE =100)
Chronic
Non-
cancer
(benchmark
MOE =100)
Cancer
(benchmark
= 10"4)
Acute Non-
cancer
(benchmark
MOE =100)
Chronic
Non-
cancer
(benchmark
MOE =100)
Cancer
(benchmark
= 10"4)
ONU
Inhalation
Model
Central
Tendency
10
62
5.8E-04
N/A
N/A
N/A
High-end
4
22
1.8E-03
N/A
N/A
N/A
Liquid cleaner
(e.g., coin and
scissor cleaner)
Other Uses (see
Section
2.3.1.20)
See Section 2.3.1.20
Liquid spray/
aerosol cleaner
Industrial /
commercial
use - Other
uses
Automotive care
products -
engine
degreaser, brake
cleaner
Aerosol Spray
Degreaser/
Cleaner
See Aerosol Spray Degreaser/Cleaner
Building/
construction
materials not
covered
elsewhere -
insulation
THERMAX™
Installation (see
Section
2.3.1.19)
See Section 2.3.1.19
Other uses (e.g.,
Arts, crafts and
hobby materials,
anti-adhesive
agents,
functional fluids,
etc.)
Other uses (see
Section
2.3.1.20)
See Section 2.3.1.20
Disposal
Municipal waste
incinerator
Off-site waste
transfer
Disposal,
Recycling (see
Section
2.3.1.21 )2
Worker
Inhalation
Model
Central
Tendency
4,441
6,235
6.1E-06
-
-
-
High-end
300
421
1.2E-04
-
-
1.2E-05
(APF 10)
Dermal
Model
Central
Tendency
405
569
6.5E-05
-
-
-
Page 313 of 486
-------
Life Cycle
Stage /
Category
Subcategory
Occupational
Exposure
Scenario
Population
Exposure
Route
and
Duration
Exposure
Est.
Method
Exposure
Level
Risk Estimates for No PPE
Risk Estimates with PPE
Acute Non-
cancer
(benchmark
MOE =100)
Chronic
Non-
cancer
(benchmark
MOE =100)
Cancer
(benchmark
= 10"4)
Acute Non-
cancer
(benchmark
MOE =100)
Chronic
Non-
cancer
(benchmark
MOE =100)
Cancer
(benchmark
= 10"4)
High-end
135
190
2.5E-04
-
-
5.0E-05
(PF5)
1 Based on the process and work activity description exposure to ONUs at the manufacturing facility is expected to be negligible.
2 Because the model assumes tank truck and railcar loading/unloading occurs outdoors, EPA expects ONU exposure to be negligible due to airborne concentration
dilution in ambient air.
Page 314 of 486
-------
4.5.2.2 Summary of Risk Estimates for Consumer Users and Bystanders
Table 4-59 summarizes the risk estimates for consumer inhalation and dermal exposure scenarios
evaluated for 1-BP. Risk estimates showing increased risk or excess cancer risks are presented in
shaded cells. The consumer exposure assessment and risk characterization are described in more
detail in Sections 2.3.2, 4.2.3, and 4.2.5.
The risk summary below is based on the POD selected from among the most sensitive acute and
chronic non-cancer endpoints, and three cancer endpoints. EPA selected developmental effects
(Post Implantation Loss) based on NLogistic modeling as the most sensitive acute and chronic non-
cancer endpoints as well as cancer endpoint (IUR of 6.00E-03). EPA presents only the comparison
to the 1.00E-06 cancer benchmark in Table 4-59.
Inhalation Exposure
Non-cancer effects following acute inhalation exposure were evaluated for all nine consumer
conditions of use identified in Table 2-31. Non-cancer and cancer effects following chronic
inhalation exposures were only evaluated for the insulation (off-gassing) condition of use.
Inhalation exposures are based on multi-zone modeling approaches for air concentrations (rather
than dose) and therefore independent of any age-specific exposure factors. As a result, the risk
estimates associated with inhalation exposure are applicable to all age groups (infant to elderly)
and PESS.
Risks for non-cancer effects following acute inhalation exposure were identified for all conditions
of use evaluated for the consumer user. Risks for non-cancer effects following acute inhalation
exposure were identified for most conditions of use evaluated for the bystander except several low
intensity use scenarios (aerosol spray degreaser/cleaner-electronics, spot cleaner and stain remover,
adhesive accelerant, and mold cleaning and release products) and all locations evaluated for the
insulation (off-gassing) condition of use for both building configurations evaluated. Risks for non-
cancer or cancer effects following chronic inhalation exposure were not identified for any of the
locations evaluated for the insulation (off-gassing) condition of use in either building configuration
evaluated.
Dermal Exposure
Risks for non-cancer effects following acute dermal exposure were identified for four of the eight
conditions of use evaluated for dermal exposure (aerosol spray degreaser/cleaner-general, spot
cleaner and stain remover, spray cleaner-general, and automobile AC flush). Dermal exposure was
evaluated for three consumer user age groups Bystanders were not evaluated for dermal exposure
as they are not expected to receive a dermal exposure.
Page 315 of 486
-------
Table 4-59. Consumer Risk Summary Table
Life Cycle
Stage
Category/
(Subcategory)
Assessed Condition
of Use
Scenario
Description
Intensity of
Use/
Location
Risk Estimates (Inhalation)
Risk Estimates (Dermal)
Acute Non-Cancer
Benchmark= 100
Chronic
Non-Cancer
Benchmark
=100
Chronic
Cancer
Benchmark
=lE-06
Acute Non-Cancer
Benchmark=100
User
Bystander
Bystander
Bystander
Adult
Youth A
Youth B
Consumer
Use
Solvent (for cleaning or
degreasing)/
(Aerosol spray
degreaser/cleaner)
Aerosol Spray
Degreaser/Cleaner-
General
High
4.3E-02
0.15
N/A
N/A
3.1
3.3
3.1
Moderate
0.32
1.2
N/A
N/A
48
50
46
Low
6.0
24
N/A
N/A
647
688
647
Aerosol Spray
Degreaser/Cleaner-
Electronics
High
0.20
0.69
N/A
N/A
239
256
234
Moderate
4.3
17
N/A
N/A
324
344
314
Low
90
316
N/A
N/A
458
500
458
Cleaning and Furniture Care
Products/ (Spot cleaner and
stain remover)
Spot Cleaner and
Stain Remover
High
0.13
0.83
N/A
N/A
13
14
12
Moderate
1.8
11
N/A
N/A
121
129
118
Low
23
125
N/A
N/A
2558
2683
2500
Cleaning and Furniture Care
Products/
(Liquid cleaner-e.g., coin and
scissors cleaner)
Coin and Scissors
Cleaner
High
3.0
6.0
N/A
N/A
145
155
143
Moderate
4.0
13
N/A
N/A
289
314
282
Low
5.0
27
N/A
N/A
846
917
846
Cleaning and Furniture Care
Products/
(Liquid spray/aerosol
cleaner)
Spray Cleaner-
General
High
4.5E-02
0.18
N/A
N/A
3.1
3.3
3.1
Moderate
0.43
2.2
N/A
N/A
25
26
24
Low
2.6
14
N/A
N/A
186
200
180
Other Uses/
(Arts, crafts, and hobby
materials-adhesive
accelerant)
Adhesive Accelerant
High
0.33
1.3
N/A
N/A
229
244
224
Moderate
5.5
30
N/A
N/A
229
244
224
Low
50
240
N/A
N/A
229
244
224
Other Uses/
(Automotive care products-
refrigerant flush)
Automobile AC
Flush
High
7.5
12
N/A
N/A
22
23
21
Moderate
11
25
N/A
N/A
22
23
21
Low
16
80
N/A
N/A
22
23
21
Other Uses/
Mold Cleaning and
Release Product
High
0.29
1.4
N/A
N/A
256
275
250
Moderate
4.3
22
N/A
N/A
393
423
379
Page 316 of 486
-------
Life Cycle
Stage
Category/
(Subcategory)
Assessed Condition
of Use
Scenario
Description
Intensity of
Use/
Location
Risk Estimates (Inhalation)
Risk Estimates (Dermal)
Acute Non-Cancer
Benchmark= 100
Chronic
Non-Cancer
Benchmark
=100
Chronic
Cancer
Benchmark
=lE-06
Acute Non-Cancer
Benchmark=100
User
Bystander
Bystander
Bystander
Adult
Youth A
Youth B
(Anti-adhesive agent-mold
cleaning and release product)
Low
50
231
N/A
N/A
733
786
733
Other Uses/
(Building construction
materials not covered
elsewhere-insulation)
Insulation (off-
gassing)
Attic/Living
Space/Crawlspace
Attic
N/A
3,030
1.2E+05
2.9E-07
N/A
N/A
N/A
Living
Space
N/A
6,663
3.1E+05
1.2E-07
N/A
N/A
N/A
Crawlspace
N/A
2,800
1.4E+05
2.7E-07
N/A
N/A
N/A
Insulation (off-
gassing)
Attic/Living
Space/Basement
Attic
N/A
3,077
1.2E+05
2.9E-07
N/A
N/A
N/A
Living
Space
N/A
18,863
7.6E+05
4.7E-08
N/A
N/A
N/A
Basement
N/A
2,869
1.3E+05
2.8E-07
N/A
N/A
N/A
Page 317 of 486
-------
4.5.2.3 Summary of Risk for General Population
EPA considered reasonably available information to characterize general population exposure and
risk. As described in the Problem Formulation and in Section 1.4.2, there are no data of 1-BP
found in U.S. drinking water. TRI reporting from 2016 indicates zero pounds released to POTWs
and five pounds released directly to water from one facility. TRI reporting from 2017 and 2018
indicate only one pound per year released to water. 1-BP is slightly soluble in water, is somewhat
biodegradable, volatilizes rapidly from water, and has a relatively high Henry's law constant. As
such, 1-BP is not expected to be present in drinking water supplied from public water systems or
sorb to solids in wastewater.
Additionally, 1-BP is not expected to adsorb strongly to sediment or soil based on its log Koc of
1.6. If present in biosolids, 1-BP would be expected to associate with the aqueous component and
volatilize to air as the biosolids are applied to soil and allowed to dry. Due to its water solubility
and low sorption, some 1-BP associated with land applied sludge could migrate with water towards
groundwater; however, volatilization and biodegradation may attenuate migration.
Based on this information and environmental fate properties, EPA does not expect general
population exposure from contaminated drinking water, surface water, or sediment via the oral and
dermal routes. Therefore, EPA did not identify risk for the general population for these pathways.
Page 318 of 486
-------
5 UNREASONABLE RISK DETERMINATION
5.1 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 environment 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 Chemical Risk Evaluation Under the Amended Toxic
Substances Control Act (82 5).40
This section describes the final unreasonable risk determinations for the conditions of use in the scope of
the risk evaluation. The final unreasonable risk determinations are based on the risk estimates in the final
risk evaluation, which may differ from the risk estimates in the draft risk evaluation due to peer review
and public comments. Therefore, the final unreasonable risk determinations of some conditions of use may
differ from those in the draft risk evaluation.
5.1.1 Human Health
EPA's risk evaluation identified non-cancer adverse effects from acute and chronic inhalation and dermal
exposures to 1-BP, and cancer from chronic inhalation and dermal exposures to 1-BP. The health risk
estimates for all conditions of use in Section 4.5 (Table 4-58 and Table 4-59).
For the 1-BP risk evaluation, EPA identified as Potentially Exposed or Susceptible Subpopulations:
workers and ONUs, including men, women of reproductive age, and adolescents; and consumer uses and
bystanders (of any age group, including infants, toddlers, children, and elderly).
EPA evaluated exposures to workers, ONUs, consumer users, and bystanders using reasonably available
monitoring and modeling data for inhalation and dermal exposures, as applicable. For example, EPA
assumed that ONUs and bystanders do not have direct contact with 1-BP; therefore, non-cancer effects and
cancer from dermal exposures to 1-BP were not evaluated. The description of the data used for human
health exposure is in Section 2.3. Uncertainties in the analysis are discussed in Section 4.3 and considered
40 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.
Page 319 of 486
-------
in the unreasonable risk determination for each condition of use presented below, including the fact that
the dermal model used does not address variability in exposure duration and frequency.
EPA considered reasonably available information and environmental fate properties to characterize
general population exposure from contaminated drinking water, surface water, or sediment via the
oral and dermal routes. EPA does not expect general population exposure from contaminated
drinking water, surface water, or sediment via the oral and dermal routes. EPA has made no
unreasonable risk determinations to the general population from all conditions of use from drinking
water, surface water, and sediment pathways (Section 5.2.1.26). EPA did not evaluate risk to the
general population from ambient air and disposal pathways for any conditions of use, and the no
unreasonable risk determinations do not account for any risk to the general population from
ambient air and disposal pathways. Additional details regarding the general population are in
Sections 1.4.2. and 4.5.2.3.
5.1.1.1 Non-Cancer Risk Estimates
The risk estimates of non-cancer effects (MOEs) refer to 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 (NOAEL) or benchmark dose level (BMDL))
for a specific health endpoint divided by the exposure concentration for the specific scenario of concern.
Section 3.2.8 presents the PODs for non-cancer effects for 1-BP and Section 4.2 presents the MOEs for
non-cancer effects.
The MOEs are compared to a benchmark MOE. The benchmark MOE accounts for the total uncertainty 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 subchronic to chronic
exposure); and (4) the uncertainty in extrapolating from a lowest observed adverse effect level (LOAEL)
rather than from a NOAEL. 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 for specific endpoints and scenarios.
However, these are often not the only uncertainties in a risk evaluation. The benchmark MOE for acute
and chronic non-cancer risks for 1-BP is 100 (accounting for interspecies and intraspecies variability).
Additional information regarding the benchmark MOE is in Section 4.2.1.
5.1.1.2 Cancer Risk Estimates
Cancer risk estimates represent the incremental increase in probability of an individual in an exposed
population developing cancer over a lifetime (excess lifetime cancer risk (ELCR)) following exposure to
the chemical. Standard cancer benchmarks used by EPA and other regulatory agencies are an increased
cancer risk above benchmarks ranging from 1 in 1,000,000 to 1 in 10,000 (i.e., lxlO"6 to lxlO"4)
Page 320 of 486
-------
depending on the subpopulation exposed.41 For this risk evaluation, EPA used lxlO"6 as the benchmark for
the cancer risk to consumers and bystanders from consumer use of insulation.
EPA, consistent with 2017 NIOSH guidance,42 used lxlO"4 as the benchmark for the purposes of this
unreasonable risk determination for individuals in industrial and commercial work environments. The
lxlO"4 value is not a bright line and EPA has discretion to make unreasonable risk determinations based on
other benchmarks as appropriate.
5.1.1.3 Determining Unreasonable Risk of Injury to Health
Calculated risk estimates (MOEs or cancer risk estimates) can provide a risk profile by presenting a range
of estimates for different health effects for different conditions of use. A calculated MOE that is less than
the benchmark MOE supports a determination of unreasonable risk of injury to health, based on non-
cancer effects. Similarly, a calculated cancer risk estimate that is greater than the cancer benchmark
supports a determination of unreasonable risk of injury to health from cancer. Whether EPA makes a
determination of unreasonable risk depends upon other risk-related factors, such as the endpoint under
consideration, the reversibility of effect, exposure-related considerations (e.g., duration, magnitude, or
frequency of exposure, or population exposed), and the confidence in the information used to inform the
hazard and exposure values. A calculated MOE greater than the benchmark MOE or a calculated cancer
risk estimate less than the cancer benchmark, alone do not support a determination of unreasonable risk,
since EPA may consider other risk-based factors when making an unreasonable risk determination.
When making an unreasonable risk determination based on injury to health of workers (who are
one example of PESS), EPA also makes assumptions regarding workplace practices and the
implementation of the required hierarchy of controls from OSHA. EPA assumes that feasible
exposure controls, including engineering controls, administrative controls, or use of personal
protective equipment (PPE) are implemented in the workplace. While OSHA has not issued a
specific PEL for 1-BP, some level of PPE is assumed to be used due to the hazard alert for
occupational exposure to 1-BP jointly issued by OSHA and NIOSH in 2013, and the Threshold
Limit Value™ (TLV™) adopted in 2014 by the American Conference of Governmental Industrial
Hygienists (ACGIH™). EPA's decisions for unreasonable risk to workers are based on high-end
exposure estimates, in order to capture not only exposures for PESS but also to account for the
41 As an example, when EPA's Office of Water in 2017 updated the Human Health Benchmarks for Pesticides, the
benchmark for a "theoretical upper-bound excess lifetime cancer risk" from pesticides in drinking water was identified
as 1 in 1,000,000 to 1 in 10,000 over a lifetime of exposure (EPA. Human Health Benchmarks for Pesticides: Updated
2017 Technical Document (pp.5). (EPA 822-R -17 -001). Washington, DC: U.S. Environmental Protection Agency,
Office of Water. January 2017. https://www.epa.gov/sites/production/files/2015-10/documents/hh-benchmarks-
techdoc.pdf). Similarly, EPA's approach under the Clean Air Act to evaluate residual risk and to develop standards is a
two-step approach that "includes a presumptive limit on maximum individual lifetime [cancer] risk (MIR) of
approximately 1 in 10 thousand" and consideration of whether emissions standards provide an ample margin of safety
to protect public health "in consideration of all health information, including the number of persons at risk levels
higher than approximately 1 in 1 million, as well as other relevant factors" (54 FR 38044, 38045, September 14, 1989).
42 NIOSH Current intelligence bulletin 68: NIOSH chemical carcinogen policy (Whittaker et al.. 2016).
Page 321 of 486
-------
uncertainties related to whether or not workers are using PPE. However, EPA does not assume that
ONUs use PPE. For each condition of use, depending on the reasonably available information and
professional judgement, EPA assumes the use of respirators with APFs ranging from 10 to 50, and
gloves with a PF of 5. However, EPA assumes that for some conditions of use, the use of
respirators is not a standard industry practice, based on professional judgement given the burden
associated with the use of respirators, including the expense of the equipment and the necessity of
fit-testing and training for proper use. Similarly, EPA does not assume that as a standard industry
practice that workers in dry cleaning facilities use gloves. Once EPA has applied the appropriate
PPE assumption for a particular condition of use in each unreasonable risk determination, in those
instances when EPA assumes PPE is used, EPA also assumes that the PPE is used in a manner that
achieves the stated APF or PF.
In the 1-BP risk characterization, developmental toxicity (i.e., post-implantation loss) was
identified as the most sensitive endpoint for non-cancer adverse effect from acute and chronic
inhalation and dermal exposures for all conditions of use. However, additional risks associated
with other adverse effects (e.g., additional developmental toxicity, reproductive toxicity, liver
toxicity, kidney toxicity, neurotoxicity) were identified for acute and chronic inhalation and dermal
exposures. Determining unreasonable risk by using developmental toxicity will also include the
unreasonable risk from other endpoints resulting from acute or chronic inhalation or dermal
exposures.
The 1-BP risk determination considers the uncertainties associated with the reasonably available
information to justify the linear cancer dose-response model when compared to other available models.
The cancer analysis is described in Section 3.2.2. EPA considered cancer risks estimates from chronic
dermal or inhalation exposures in the unreasonable risk determination.
When making a determination of unreasonable risk, the Agency has a higher degree of confidence where
uncertainty is low. Similarly, EPA has high confidence in the hazard and exposure characterizations when,
for example, the basis for characterizations is measured or monitoring data or a robust model and the
hazards identified for risk estimation are relevant for conditions of use. Where EPA has made assumptions
in the scientific evaluation, whether or not those assumptions are protective is also a consideration.
Additionally, EPA considers the central tendency and high-end exposure levels when determining the
unreasonable risk. High-end risk estimates (e.g., 95th percentile) are generally intended to cover
individuals or sub-populations with greater exposure (PESS) as well as to capture individuals with sentinel
exposure, and central tendency risk estimates are generally estimates of average or typical exposure.
EPA may make a determination of no unreasonable risk for conditions of use where the substance's hazard
and exposure potential, or where the risk-related factors described previously, lead the Agency to
determine that the risks are not unreasonable.
Page 322 of 486
-------
5.1.2 Environment
EPA calculated a risk quotient (RQ) to compare environmental concentrations against an effect level. The
environmental concentration is determined based on the levels of the chemical released to the environment
(e.g., surface water, sediment, soil, biota) under the conditions of use, based on the fate properties, release
potential, and reasonably available environmental monitoring data. The effect level is calculated using
concentrations of concern that represent hazard data for aquatic, sediment-dwelling, and terrestrial
organisms. Section 4.1 provides more detail regarding the risk quotient for 1-BP.
5.1.2.1 Determining Unreasonable Risk of Injury to the Environment
An RQ equal to 1 indicates that the exposures are the same as the concentration that causes effects. An RQ
less than 1, when the exposure is less than the effect concentration, supports a determination that there is
no unreasonable risk of injury to the environment. An RQ greater than 1, when the exposure is greater than
the effect concentration, supports a determination that there is unreasonable risk of injury to the
environment. Consistent with EPA's human health evaluations, other risk-based factors may be considered
(e.g., confidence in the hazard and exposure characterization, duration, magnitude, uncertainty) for
purposes of making an unreasonable risk determination.
EPA considered the effects on the aquatic, sediment dwelling and terrestrial organisms. EPA provides
estimates for environmental risk in Section 4.1 and Table 4-2.
5.2 Detailed Unreasonable Risk Determinations by Condition of Use
Table 5-1. Categories and Subcategories of Conditions of Use Included in the Scope of the Risk
Evaluation
Life Cycle
Stage
Category a
Subcategory b
Unreasonable
Risk
Detailed Risk
Determination
Manufacture
Domestic manufacture
Domestic manufacture
No
Sections 5.2.1.1,
5.2.1.26, and 5.2.2
Import
Import
No
Sections 5.2.1.2,
5.2.1.26, and 5.2.2
Page 323 of 486
-------
Table 5-1. Categories and Subcategories of Conditions of Use Included in the Scope of the Risk
Evaluation
Life Cycle
Stage
Category a
Subcategory b
Unreasonable
Risk
Detailed Risk
Determination
Processing
Processing as a reactant
Intermediate in all other basic
inorganic chemical
manufacturing, all other basic
organic chemical
manufacturing, and pesticide,
fertilizer and other
agricultural chemical
manufacturing
No
Sections 5.2.1.3,
5.2.1.26, and 5.2.2.
Processing
Processing -
incorporation into
formulation, mixture or
reaction products
Solvents for cleaning or
degreasing in manufacturing
of:
- all other chemical product
and preparation
- computer and electronic
product
- electrical equipment,
appliance and component
- soap, cleaning compound
and toilet preparation
- services
Yes
Sections 5.2.1.4,
5.2.1.26, and 5.2.2
Processing
Processing -
incorporation into articles
Solvents (becomes part of
product formulation or
mixture) in construction
No
Sections 5.2.1.5,
5.2.1.26, and 5.2.2
Processing
Repackaging
Solvents (cleaning or
degreasing in all other basic
organic chemical
manufacturing)
No
Sections 5.2.1.6,
5.2.1.26, and 5.2.2
Processing
Recycling
Recycling
No
Sections 5.2.1.7,
5.2.1.26, and 5.2.2
Distribution in
commerce
Distribution
Distribution
No
Sections 5.2.1.8,
5.2.1.26, and 5.2.2
Page 324 of 486
-------
Table 5-1. Categories and Subcategories of Conditions of Use Included in the Scope of the Risk
Evaluation
Life Cycle
Stage
Category a
Subcategory b
Unreasonable
Risk
Detailed Risk
Determination
Industrial/
commercial use
Solvent (for cleaning or
degreasing)
Batch vapor degreaser (e.g.,
open-top, closed-loop)
Yes
Batch vapor degreaser
(open-top) - Sections
5.2.1.9, 5.2.1.26, and
5.2.2.
Batch vapor degreaser
(closed-loop) -
Sections 5.2.1.10,
5.2.1.26, and 5.2.2
In-line vapor degreaser (e.g.,
conveyorized, web cleaner)
Yes
Sections 5.2.1.9,
5.2.1.26, and 5.2.2.
Cold cleaner
Yes
Sections 5.2.1.11,
5.2.1.26, and 5.2.2
Aerosol spray
degreaser/cleaner
Yes
Sections 5.2.1.12,
5.2.1.26, and 5.2.2
Adhesives and sealants
Adhesive chemicals - spray
adhesive for foam cushion
manufacturing and other uses
Yes
Sections 5.2.1.13,
5.2.1.26, and 5.2.2
Cleaning and furniture
care products
Dry cleaning solvent
Yes
Sections 5.2.1.14,
5.2.1.26, and 5.2.2.
Spot cleaner, stain remover
Yes
Sections 5.2.1.14,
5.2.1.26, and 5.2.2
Liquid cleaner (e.g., coin and
scissor cleaner)
Yes
Sections 5.2.1.15,
5.2.1.26, and 5.2.2
Liquid spray/aerosol cleaner
Yes
Sections 5.2.1.15,
5.2.1.26, and 5.2.2
Other uses
Arts, crafts and hobby
materials - adhesive
accelerant
Yes
Sections 5.2.1.16,
5.2.1.26, and 5.2.2
Automotive care products -
engine degreaser, brake
cleaner
Yes
Sections 5.2.1.16,
5.2.1.26, and 5.2.2
Anti-adhesive agents - mold
cleaning and release product
Yes
Sections 5.2.1.16,
5.2.1.26, and 5.2.2
Page 325 of 486
-------
Table 5-1. Categories and Subcategories of Conditions of Use Included in the Scope of the Risk
Evaluation
Life Cycle
Stage
Category a
Subcategory b
Unreasonable
Risk
Detailed Risk
Determination
Building/construction
materials not covered
elsewhere - insulation
No
Sections 5.2.1.24,
5.2.1.26, and 5.2.2
Electronic and electronic
products and metal products
Yes
Sections 5.2.1.16,
5.2.1.26, and 5.2.2
Functional fluids (closed
systems) - refrigerant
Yes
Sections 5.2.1.16,
5.2.1.26, and 5.2.2
Functional fluids (open
system) - cutting oils
Yes
Sections 5.2.1.16,
5.2.1.26, and 5.2.2
Other - asphalt extraction
Yes
Sections 5.2.1.16,
5.2.1.26, and 5.2.2
Other - Laboratory chemicals0
Yes
Sections 5.2.1.16,
5.2.1.26, and 5.2.2
Temperature Indicator -
Coatings
Yes
Sections 5.2.1.16,
5.2.1.26, and 5.2.2
Consumer uses
Solvent (cleaning or
degreasing)
Aerosol spray
degreaser/cleaner
Yes
Sections 5.2.1.17,
5.2.1.26, and 5.2.2
Cleaning and furniture
care products
Spot cleaner, stain remover
Yes
Sections 5.2.1.18,
5.2.1.26, and 5.2.2
Liquid cleaner (e.g., coin and
scissor cleaner)
Yes
Sections 5.2.1.19,
5.2.1.26, and 5.2.2
Liquid spray/aerosol cleaner
Yes
Sections 5.2.1.20,
5.2.1.26, and 5.2.2
Other uses
Arts, crafts and hobby
materials - adhesive
accelerant
Yes
Sections 5.2.1.21,
5.2.1.26, and 5.2.2
Automotive care products -
refrigerant flush
Yes
Sections 5.2.1.22,
5.2.1.26, and 5.2.2
Anti-adhesive agents - mold
cleaning and release product
Yes
Section 5.2.1.23,
5.2.1.26, and 5.2.2
Page 326 of 486
-------
Table 5-1. Categories and Subcategories of Conditions of Use Included in the Scope of the Risk
Evaluation
Life Cycle
Stage
Category a
Subcategory b
Unreasonable
Risk
Detailed Risk
Determination
Building/construction
materials not covered
elsewhere - insulation
No
Sections 5.2.1.24,
5.2.1.26, and 5.2.2
Disposal
(Manufacturing,
Processing, Use)
Disposal
Municipal waste incinerator
No
Sections 5.2.1.25,
5.2.1.26, and 5.2.2
Off-site waste transfer
a These categories of conditions of use appear in the Life Cycle Diagram, reflect CDR codes, and broadly represent additional
information regarding all conditions of use of 1-BP.
b These subcategories reflect more specific information regarding the conditions of use of 1-BP.
0 "Other - Laboratory Chemicals" was changed from "Temperature Indicator - Laboratory Chemicals" since the problem form
because other uses of 1-BP as a laboratory chemical were identified.
Although EPA has identified both industrial and commercial uses here for purposes of distinguishing scenarios in this document, the Agency
interprets the authority over "any manner or method of commercial use" under TSCA section 6(a)(5) to reach both.
5.2.1 Human Health
5.2.1.1 Manufacture - Domestic Manufacture (Domestic manufacture)
Section 6(b)(4)(A) unreasonable risk determination for domestic manufacture of 1-BP: Does not present
an unreasonable risk of injury to health (workers and ONUs).
For workers, EPA found that there was no unreasonable risk of non-cancer effects (developmental) from
acute and chronic inhalation and dermal exposures at the central tendency and high-end, when assuming
use of PPE. In addition, for workers, EPA found that there was no unreasonable risk of cancer from
chronic inhalation or dermal exposures at the central tendency and high-end, when assuming use of PPE.
For ONUs, EPA found that there was no unreasonable risk of non-cancer effects (developmental) from
acute and chronic inhalation exposures or of cancer from chronic inhalation exposures.
EPA's determination that the domestic manufacturing of 1-BP does not present an unreasonable risk is
based on the comparison of the risk estimates for non-cancer effects and cancer to the benchmarks (Table
4-58) and other considerations. As explained in Section 5.1., EPA considered the health effects of 1-BP,
the exposures from the condition of use, and the uncertainties in the analysis (Section 4.3), including
uncertainties related to the exposures for ONUs:
• For workers, when assuming the use of respirators with APF of 10 and gloves with PF of 5, the
risk estimates of non-cancer effects from acute and chronic inhalation exposures at the high-end,
Page 327 of 486
-------
risk estimates of cancer from inhalation exposures at the high-end, and risk estimates of cancer
from dermal exposures at the high-end do not support an unreasonable risk determination.
Respirators with APF of 10 and gloves with PF of 5 are the assumed personal protective equipment
for workers at manufacturing facilities, based on process and work activity descriptions at a
manufacturing facility.
• Inhalation exposures were assessed using personal breathing zone monitoring data reflective of
current operations at one manufacturing facility and may not represent activities at other
manufacturing facilities.
• Though inhalation exposures monitoring was not performed for occupational non-users at the
manufacturing facility, based on the process and work activity description, inhalation exposures to
ONUs are assumed to be negligible.
• Dermal exposures were assessed using modeled data.
In summary, the risk estimates, the health effects of 1-BP, the exposures, and consideration of
uncertainties support EPA's determination that there is no unreasonable risk of injury to health (workers
and ONUs) from domestic manufacturing of 1-BP.
5.2.1.2 Manufacture - Import (Import)
Section 6(b)(4)(A) unreasonable risk determination for import of 1-BP: Does not present an unreasonable
risk of injury to health (workers and ONUs).
For workers, EPA found that there was no unreasonable risk of non-cancer effects (developmental) from
acute and chronic inhalation and dermal exposures at the central tendency and high-end, even when PPE is
not used. In addition, for workers, EPA found that there was no unreasonable risk of cancer from chronic
inhalation and dermal exposures at the central tendency and high-end, when assuming use of PPE. For
ONUs, EPA found that there was no unreasonable risk of non-cancer effects (developmental) from acute
and chronic inhalation exposures and of cancer from chronic inhalation exposures.
EPA's determination that the import of 1-BP does not present an unreasonable risk is based on the
comparison of the risk estimates for non-cancer effects (developmental) and cancer to the benchmarks
(Table 4-58) and other considerations. As explained in Section 5.1., EPA considered the health effects of
1-BP, the exposures from the condition of use, and the uncertainties in the analysis (Section 4.3), including
uncertainties related to the exposures for ONUs:
• For workers, when assuming the use of respirators with APF of 10 and gloves with PF of 5, the
risk estimates of cancer from chronic inhalation and dermal exposures at the high-end do not
support an unreasonable risk determination. Respirators with APF of 10 and gloves with PF of 5
are the assumed personal protective equipment for workers at importing facilities, based on
professional judgement regarding practices at an importing facility.
• Inhalation exposures were assessed using modeled data. The model is representative of exposures
associated with bulk container loading; however, the model does not account for other potential
sources of exposure at industrial facilities, such as sampling or equipment cleaning.
Page 328 of 486
-------
• The uncertainties include the inhalation exposures for ONUs, which are assumed to be negligible
due to the dilution of 1-BP into the ambient air in the model used.
• Dermal exposures were assessed using modeled data.
In summary, the risk estimates, the health effects of 1-BP, the exposures, and consideration of
uncertainties support EPA's determination that there is no unreasonable risk of injury to health (workers
and ONUs) from import of 1-BP.
5.2.1.3 Processing - Processing as a reactant - Intermediate in all other basic
inorganic chemical manufacturing, all other basic organic chemical
manufacturing, and pesticide, fertilizer, and other agricultural chemical
manufacturing (Processing as reactant)
Section 6(b)(4)(A) unreasonable risk determination for the processing of 1-BP as a reactant: Does not
present an unreasonable risk of injury to health (workers and ONUs).
For workers, EPA found that there was no unreasonable risk of non-cancer effects (developmental) from
acute and chronic inhalation or dermal exposures at the central tendency and high-end, even when PPE is
not used. In addition, for workers, EPA found that there was no unreasonable risk of cancer from chronic
inhalation or dermal exposures at the central tendency and high-end, when assuming use of PPE. For
ONUs, EPA found that there was no unreasonable risk of non-cancer effects (developmental) from acute
and chronic inhalation exposures and of cancer from chronic inhalation exposures.
EPA's determination that processing of 1-BP as a reactant does not present an unreasonable risk is based
on the comparison of the risk estimates for non-cancer effects and cancer to the benchmarks (Table 4-58)
and other considerations. As explained in Section 5.1., EPA considered the health effects of 1-BP, the
exposures from the condition of use, and the uncertainties in the analysis (Section 4.3), including
uncertainties related to the exposures for ONUs:
• For workers, when assuming the use of respirators with APF of 10 and gloves with PF of 5, the
risk estimates of cancer from chronic inhalation and dermal exposures at the high-end do not
support an unreasonable risk determination. Respirators with APF of 10 and gloves with PF of 5
are the assumed personal protective equipment for workers at processing facilities, based on
professional judgement regarding practices at processing facilities.
• Inhalation exposures were assessed using modeled data. The model is representative of exposures
associated with bulk container loading; however, the model does not account for other potential
sources of exposure at processing facilities, such as sampling or equipment cleaning.
• Inhalation exposures for ONUs are assumed to be negligible due to the dilution of 1-BP into the
ambient air in the model used.
• Dermal exposures were also assessed using modeled data.
In summary, the risk estimates, the health effects of 1-BP, the exposures, and consideration of
uncertainties support EPA's determination that there is no unreasonable risk of injury to health (workers
and ONUs) from processing of 1-BP as a reactant.
Page 329 of 486
-------
5.2.1.4 Processing - Incorporation into formulation, mixture, or reaction
products - Solvents for cleaning or degreasing in manufacturing of: all other
chemical product and preparation; computer and electronic product; electrical
equipment, appliance and component; soap, cleaning compound and toilet
preparation; and services (Processing into a formulation, mixture, or reaction
product)
Section 6(b)(4)(A) unreasonable risk determination for processing of 1-BP into a formulation, mixture, or
reaction product: Presents an unreasonable risk of injury to health (workers and ONUs).
For workers, EPA found that there was unreasonable risk of cancer from chronic inhalation
exposures, even when assuming use of PPE. For ONUs, EPA found that there was unreasonable risk
of non-cancer effects (developmental) from acute and chronic inhalation exposures at the high-end
and of cancer from chronic inhalation exposures at the central tendency and high-end.
EPA's determination that the processing of 1-BP into a formulation, mixture, or reaction product presents
an unreasonable risk is based on the comparison of the risk estimates for non-cancer effects and cancer to
the benchmarks (Table 4-58) and other considerations. As explained in Section 5.1., EPA considered the
health effects of 1-BP, the exposures for the condition of use, and the uncertainties in the analysis (Section
4.3):
• For workers, when assuming the use of respirators with APF of 50, the risk estimates of cancer
from chronic inhalation exposures support an unreasonable risk determination.
• For workers, when assuming the use of respirators with APF of 50, the risk estimates of
non-cancer effects from acute and chronic inhalation exposures do not support an
unreasonable risk determination. Similarly, when assuming the use of gloves with PF of 5,
the risk estimates of cancer from dermal exposures at the high-end do not support an
unreasonable risk determination. Respirators with APF of 50 and gloves with PF of 5 are
the maximum assumed personal protective equipment for workers at processing facilities,
based on professional judgement regarding practices at processing facilities.
• For workers, the risk estimates of non-cancer effects from dermal exposures do not support an
unreasonable risk determination.
• Inhalation exposures for workers and ONUs were assessed using personal breathing zone
monitoring data collected at one formulation facility. The data have a high confidence rating and
are directly applicable to this condition of use; however, the data may not be representative of
exposures across the range of facilities that formulate products containing 1-BP. Based on EPA's
analysis of the data for workers' inhalation exposures, central tendency or high-end exposures
could not be distinguished.
• Dermal exposures were assessed using modeled data.
In summary, the risk estimates, the health effects of 1-BP, the exposures, and consideration of
uncertainties support EPA's determination that there is unreasonable risk of injury to health (workers and
ONUs) from processing of 1-BP into a formulation, mixture, or reaction product.
Page 330 of 486
-------
5.2.1.5 Processing - Incorporation into articles - Solvents (becomes part of
product formulation or mixture) in construction (Processing into articles)
Section 6(b)(4)(A) unreasonable risk determination for the processing of 1-BP into articles: Does not
present an unreasonable risk of injury to health (workers and ONUs).
For workers, EPA found that there was no unreasonable risk of non-cancer effects (developmental) from
acute and chronic inhalation or dermal exposures at the central tendency and high-end, even when PPE is
not used. In addition, for workers, EPA found that there was no unreasonable risk of cancer from chronic
inhalation or dermal exposures at the central tendency and high-end, when assuming use of PPE. For
ONUs, EPA found that there was no unreasonable risk of non-cancer effects (developmental) from acute
and chronic inhalation exposures and of cancer from chronic inhalation exposures.
EPA's determination that the processing of 1-BP into articles does not present an unreasonable risk is
based on the comparison of the risk estimates for non-cancer effects and cancer to the benchmarks (Table
4-58) and other considerations. As explained in Section 5.1., EPA considered the health effects of 1-BP,
the exposures for the condition of use, and the uncertainties in the analysis (Section 4.3), including
uncertainties related to the exposures for ONUs:
• For workers, when assuming the use of respirators with APF of 10 and gloves with PF of 5, the
risk estimates of cancer from chronic inhalation and dermal exposures at the high-end do not
support an unreasonable risk determination. Respirators with APF of 10 and gloves with PF of 5
are the assumed personal protective equipment for workers at processing facilities, based on
professional judgement regarding practices at processing facilities.
• Inhalation exposures were assessed using modeled data. The model is representative of exposures
associated with bulk container loading; however, the model does not account for other potential
sources of exposure at processing facilities, such as sampling or equipment cleaning.
• Inhalation exposures for ONUs are assumed to be negligible due to the dilution of 1-BP into the
ambient air in the model used.
• Dermal exposures were also assessed using modeled data.
In summary, the risk estimates, the health effects of 1-BP, the exposures, and consideration of
uncertainties support EPA's determination that there is no unreasonable risk of injury to health (workers
and ONUs) from the incorporation of 1-BP into articles.
5.2.1.6 Processing - Repackaging - Solvents (cleaning or degreasing in all other
basic organic chemical manufacturing) (Processing in repackaging as solvent)
Section 6(b)(4)(A) unreasonable risk determination for processing in repackaging of 1-BP as solvent:
Does not present an unreasonable risk of injury to health (workers and ONUs).
For workers, EPA found that there was no unreasonable risk of non-cancer effects (developmental) from
acute and chronic inhalation or dermal exposures at the central tendency and high-end, even when PPE is
not used. In addition, for workers, EPA found that there was no unreasonable risk of cancer from chronic
inhalation or dermal exposures at the central tendency and high-end, when assuming use of PPE. For
Page 331 of 486
-------
ONUs, EPA found that there was no unreasonable risk of non-cancer effects (developmental) from acute
and chronic inhalation exposures and of cancer from chronic inhalation exposures.
EPA's determination that the processing of 1-BP in repackaging does not present an unreasonable risk is
based on the comparison of the risk estimates for non-cancer effects and cancer to the benchmarks (Table
4-58) and other considerations. As explained in Section 5.1., EPA considered the health effects of 1-BP,
the exposures for the condition of use, and the uncertainties in the analysis (Section 4.3), including
uncertainties related to the exposures for ONUs:
• For workers, when assuming the use of respirators with APF of 10 and gloves with PF of 5, the
risk estimates of cancer from chronic inhalation and dermal exposures at the high-end do not
support an unreasonable risk determination. Respirators with APF of 10 and gloves with PF of 5
are the assumed personal protective equipment for workers at processing facilities, based on
professional judgement regarding practices at processing facilities.
• Inhalation exposures were assessed using modeled data. The model is representative of exposures
associated with bulk container loading; however, the model does not account for other potential
sources of exposure at repackaging facilities, such as sampling or equipment cleaning.
• Inhalation exposures for ONUs are assumed to be negligible due to the dilution of 1-BP into the
ambient air in the model used.
• Dermal exposures were also assessed using modeled data.
In summary, the risk estimates, the health effects of 1-BP, the exposures, and consideration of
uncertainties support EPA's determination that there is no unreasonable risk of injury to health (workers
and ONUs) from the repackaging of 1-BP.
5.2.1.7 Processing - Recycling - Recycling (Processing as recycling)
Section 6(b)(4)(A) unreasonable risk determination for recycling of 1-BP: Does not present an
unreasonable risk of injury to health (workers and ONUs).
For workers, EPA found that there was no unreasonable risk of non-cancer effects (developmental) from
acute and chronic inhalation or dermal exposures at the central tendency and high-end, even when PPE is
not used. In addition, for workers, EPA found that there was no unreasonable risk of cancer from chronic
inhalation or dermal exposures at the central tendency and high-end, when assuming use of PPE. For
ONUs, EPA found that there was no unreasonable risk of non-cancer effects (developmental) from acute
and chronic inhalation exposures and of cancer from chronic inhalation exposures.
EPA's determination that the processing of 1-BP in recycling does not present an unreasonable risk is
based on the comparison of the risk estimates for non-cancer effects and cancer to the benchmarks (Table
4-58) and other considerations. As explained in Section 5.1., EPA considered the health effects of 1-BP,
the exposures for the condition of use, and the uncertainties in the analysis (Section 4.3), including
uncertainties related to the exposures for ONUs:
• For workers, when assuming the use of respirators with APF of 10 and gloves with PF of 5, the
risk estimates of cancer from chronic inhalation and dermal exposures at the high-end do not
Page 332 of 486
-------
support an unreasonable risk determination. Respirators with APF of 10 and gloves with PF of 5
are the assumed personal protective equipment for workers at processing facilities, based on
professional judgement regarding practices at recycling facilities.
• Inhalation exposures were assessed using modeled data. The model is representative of exposures
associated with bulk container loading; however, the model does not account for other potential
sources of exposure at recycling facilities, such as sampling or equipment cleaning.
• Inhalation exposures for ONUs are assumed to be negligible due to the dilution of 1-BP into the
ambient air in the model used.
• Dermal exposures were also assessed using modeled data.
In summary, the risk estimates, the health effects of 1-BP, the exposures, and consideration of
uncertainties support EPA's determination that there is no unreasonable risk of injury to health (workers
and ONUs) from the recycling of 1-BP.
5.2.1.8 Distribution in Commerce
Section 6(b)(4)(A) unreasonable risk determination for distribution in commerce of 1-BP: Does not
present an unreasonable risk of injury to health (workers and ONUs).
For the purposes of the unreasonable risk determination, distribution in commerce of 1-BP is the
transportation associated with the moving of 1-BP in commerce. The loading and unloading activities are
associated with other conditions of use. EPA assumes transportation of 1-BP is in compliance with
existing regulations for the transportation of hazardous materials, and emissions are therefore minimal
(with the exception of spills and leaks, which are outside the scope of the risk evaluation). Based on the
limited emissions from the transportation of chemicals, EPA determines there is no unreasonable risk of
injury to health (workers and ONUs) from the distribution in commerce of 1-BP.
5.2.1.9 Industrial/Commercial Use - Solvent (for cleaning or degreasing) -
Batch vapor degreaser (open-top) and in-line vapor degreaser (conveyorized, web
cleaner)
Section 6(b)(4)(A) unreasonable risk determination for the industrial and commercial use of 1-BP as
solvent in batch vapor degreaser (open-top) and in-line vapor degreaser (conveyorized. web cleaner):
Presents an unreasonable risk of injury to health (workers and ONUs).
For workers, EPA found there was unreasonable risk of non-cancer effects (developmental) from
acute and chronic inhalation exposures at the high-end, and of cancer from chronic inhalation
exposures at the central tendency and high-end, even when assuming use of PPE. For ONUs, EPA
found there was unreasonable risk of non-cancer effects (developmental) from acute and chronic
inhalation exposures at the central tendency and high-end, and of cancer from chronic inhalation
exposures at the central tendency and high-end.
EPA's determination that the industrial and commercial use of 1-BP as solvent for cleaning or degreasing
in open-top batch vapor degreasers and in-line vapor degreasers presents an unreasonable risk is based on
Page 333 of 486
-------
the comparison of the risk estimates for non-cancer effects and cancer to the benchmarks (Table 4-58) and
other considerations. As explained in Section 5.1., EPA considered the health effects of 1-BP, the
exposures for the condition of use, and the uncertainties in the analysis (Section 4.3):
• For workers, when assuming the use of respirators with APF of 50, the risk estimates of non-cancer
and cancer from inhalation exposures at the high-end support an unreasonable risk determination.
• For workers, when assuming the use of gloves with PF of 5, the risk estimates of cancer from
dermal exposures at the high-end do not support an unreasonable risk determination. Gloves with
PF of 5 are the assumed worker protection at facilities with open-top batch vapor degreasers and
in-line vapor degreasers, based on professional judgement regarding practices at such facilities.
• Inhalation exposures for workers and ONUs from open-top batch vapor degreasers were assessed
using personal breathing zone monitoring data collected from several different sources; however,
some of the data do not clearly specify the type of vapor degreaser. Since open-top vapor
degreasers typically have the highest emissions, based on EPA's analysis the data may
underestimate exposures from batch vapor degreasers. The exposures data from open-top vapor
degreasers was supplemented with a peer reviewed model using emission factors developed by the
California Air Resources Board. The model results are in general agreement with monitoring data.
• There are no monitoring data specific to in-line vapor degreasers using 1-BP or data specific
enough to develop a model; however, based on National Emission Inventory data, emissions form
in-line vapor degreasers are generally similar to emissions from batch vapor degreasers.
• Dermal exposures were assessed using modeled data.
In summary, the risk estimates, the health effects of 1-BP, the exposures, and consideration of
uncertainties support EPA's determination that there is unreasonable risk of injury to health (workers and
ONUs) from the industrial and commercial use of 1-BP as solvent for cleaning or degreasing in open-top
batch vapor degreasers and in-line vapor degreasers.
5.2.1.10 Industrial/Commercial Use - Solvent (for cleaning or degreasing) -
Batch vapor degreaser (closed-loop)
Section 6(b)(4)(A) unreasonable risk determination for the industrial and commercial use of 1-BP as
solvent for batch vapor degreaser (closed-loop): Presents an unreasonable risk of injury to health
(ONUs); does not present an unreasonable risk of injury to health (workers).
For ONUs, EPA found there was unreasonable risk of non-cancer effects (developmental) from
acute and chronic inhalation exposures at the high-end and of cancer from chronic inhalation
exposures at the high-end. For workers, EPA found that there was no unreasonable risk of non-cancer
effects (developmental) from acute and chronic inhalation at central tendency and at high-end and of
cancer from chronic inhalation at central tendency and high-end, when assuming use of PPE. In addition,
for workers, EPA found that there was no unreasonable risk of non-cancer effects (developmental) from
dermal exposure, and of cancer from dermal exposure, when assuming use of PPE.
EPA's determination that the industrial and commercial use of 1-BP as solvent for cleaning or degreasing
in closed-loop batch vapor degreasers presents an unreasonable risk is based on the comparison of the risk
Page 334 of 486
-------
estimates for non-cancer effects and cancer to the benchmarks (Table 4-58) and other considerations. As
explained in Section 5.1., EPA considered the health effects of 1-BP, the exposures for the condition of
use, and the uncertainties in the analysis (Section 4.3):
• For workers, when assuming the use of respirators with APF of 10, the risk estimates of non-cancer
effects from acute and chronic inhalation exposures at the high-end, and the risk estimates of
cancer from chronic inhalation exposures at the high-end do not support an unreasonable risk
determination. Similarly, when assuming the use of gloves with PF of 5, the risk estimates of
cancer from dermal exposures at the high-end do not support an unreasonable risk determination.
Respirators with APF of 10 and gloves with PF of 5 are the assumed worker protection at facilities
using 1-BP in closed-loop vapor degreasers, based on professional judgement regarding practices
at such facilities.
• Inhalation exposures for workers and ONUs were assessed using a model with information from
the open-top vapor degreaser and assuming 98 percent exposure reduction when switching from
open-top to closed-loop.
• Dermal exposures were assessed using modeled data.
In summary, the risk estimates, the health effects of 1-BP, the exposures, and consideration of
uncertainties support EPA's determination that there is unreasonable risk of injury to health (ONUs) from
industrial and commercial use of 1-BP as solvent for cleaning or degreasing in closed-loop batch vapor
degreasers.
5.2.1.11 Industrial/Commercial Use - Solvent (for cleaning or degreasing) -
Cold cleaners
Section 6(b)(4)(A) unreasonable risk determination for the industrial and commercial use of 1-BP as
solvent in cold cleaners: Presents an unreasonable risk of injury to health (workers and ONUs).
For workers, EPA found there was unreasonable risk of cancer from chronic inhalation exposures
at the central tendency and high-end, even when assuming use of PPE. For ONUs, EPA found there
was unreasonable risk of non-cancer effects (developmental) from acute and chronic inhalation
exposures, and of cancer from chronic inhalation exposures.
EPA's determination that the industrial and commercial use of 1-BP as solvent in cold cleaners presents an
unreasonable risk is based on the comparison of the risk estimates for non-cancer effects and cancer to the
benchmarks (Table 4-58) and other considerations. As explained in Section 5.1., EPA considered the
health effects of 1-BP, the exposures for the condition of use, and the uncertainties in the analysis (Section
4.3):
• For workers, when assuming the use of respirators with APF of 50, the risk estimates of cancer
from inhalation exposures support an unreasonable risk determination.
• For workers, when assuming the use of respirators with APF of 50, the risk estimates of non-cancer
effects from inhalation exposures do not support an unreasonable risk determination. Similarly,
when assuming the use of gloves with PF of 5, the risk estimates of cancer from dermal exposures
at the high-end do not support an unreasonable risk determination. Respirators with APF of 50 and
Page 335 of 486
-------
gloves with PF of 5 are the assumed maximum worker protection at facilities with cold cleaners,
based on professional judgement regarding practices at a such facilities.
• Inhalation exposures for workers and ONUs from cold cleaners were assessed using personal
breathing zone monitoring data from OSHA inspections, which are not intended to represent
typical exposure levels at the workplace. In addition, the monitoring data may not be representative
of the exposure level for the typical ONU (resulting in similar risk estimates for inhalation
exposures at central tendency and high-end). The exposures monitoring data for cold cleaners was
supplemented with modeling using emission factors for generic non-methane VOC. Exposures
results are in good agreement with the exposure monitoring data for cold cleaners.
• Dermal exposures were assessed using modeled data.
In summary, the risk estimates, the health effects of 1-BP, the exposures, and consideration of
uncertainties support EPA's determination that there is unreasonable risk of injury to health (workers and
ONUs) from the industrial and commercial use of 1-BP as solvent in cold cleaners.
5.2.1.12 Industrial/Commercial Use - Solvent (for cleaning or degreasing) -
Aerosol spray degreaser/cleaner
Section 6(b)(4)(A) unreasonable risk determination for the industrial and commercial use of 1-BP as
solvent in aerosol spray degreasers/cleaners: Presents an unreasonable risk of injury to health
(workers and ONUs).
For workers, EPA found there was unreasonable risk of non-cancer effects (developmental) from
acute and chronic inhalation exposures at the central tendency and high-end, and of cancer from
chronic inhalation exposures at the central tendency and high-end, without assuming use of
respirators. For ONUs, EPA found there was unreasonable risk of non-cancer effects
(developmental) from acute and chronic inhalation exposures at the central tendency and high-end,
and of cancer from chronic inhalation exposures at the central tendency and high-end.
EPA's determination that the industrial and commercial use of 1-BP as solvent for cleaning or degreasing
in aerosol spray degreasers/cleaners presents an unreasonable risk is based on the comparison of the risk
estimates for non-cancer effects and cancer to the benchmarks (Table 4-58) and other considerations. As
explained in Section 5.1, EPA considered the health effects of 1-BP, the exposures for the condition of
use, and the uncertainties in the analysis (Section 4.3):
• EPA does not assume workers to use any type of respirator during industrial and commercial use of
1-BP as solvent for cleaning or degreasing in aerosol spray degreasers/cleaners.
• For workers, the risk estimates of non-cancer effects from dermal exposures do not support an
unreasonable risk determination. When assuming the use of gloves with PF of 5, the risk estimates
of cancer from dermal exposures at the high-end do not support an unreasonable risk
determination. Gloves with PF of 5 are the assumed worker protection at facilities using 1-BP in
aerosol degreasing based on professional judgement regarding practices at such facilities.
Page 336 of 486
-------
• Inhalation exposures for workers and ONUs from aerosol degreasing were assessed using a model
which provides exposure estimates for a brake cleaning scenario. Although the model scenario is
specific to brake cleaning and may not encompass the full range of aerosol degreasing uses, the
model results are in good agreement with monitoring data. EPA also considered monitoring data
from personal breathing zone collected from two studies, which indicated similar risks.
• Dermal exposures were also assessed using modeled data.
In summary, the risk estimates, the health effects of 1-BP, the exposures, and consideration of
uncertainties support EPA's determination that there is unreasonable risk of injury to health (workers and
ONUs) from industrial and commercial use of 1-BP as solvent for cleaning or degreasing in in aerosol
spray degreasers/cleaners.
5.2.1.13 Industrial/Commercial Use - Adhesives and sealants - Adhesive
chemicals (spray adhesive for foam cushion manufacturing and other uses)
Section 6(b)(4)(A) unreasonable risk determination for the industrial and commercial use of 1-BP in
adhesives and sealants: Presents an unreasonable risk of injury to health (workers and ONUs).
For workers, EPA found there was unreasonable risk of non-cancer effects (developmental) from
acute and chronic inhalation exposures at the central tendency and high-end and of cancer from
chronic inhalation exposures at the central tendency and high-end, even when assuming use of PPE.
For ONUs, EPA found there was unreasonable risk of non-cancer effects (developmental) from
acute and chronic inhalation exposures at the central tendency and high-end, and of cancer from
chronic inhalation exposures at the central tendency and high-end.
EPA's determination that the industrial and commercial use of 1-BP in adhesives and sealants presents an
unreasonable risk is based on the comparison of the risk estimates for non-cancer effects and cancer to the
benchmarks (Table 4-58) and other considerations. As explained in Section 5.1, EPA considered the health
effects of 1-BP, the exposures for the condition of use, and the uncertainties in the analysis (Section 4.3):
• The workers considered included the "sprayers" of the 1-BP adhesive and "non-sprayers" that
handle the 1-BP adhesive or spend the majority of their shift working in an area where spraying
occurs.
• For workers (sprayers and non-sprayers), when assuming the use of respirators with APF of 50, the
risk estimates of non-cancer effects from acute and chronic inhalation exposures, and the risk
estimates of cancer from chronic inhalation exposures support an unreasonable risk determination.
• For workers (sprayers and non-sprayers), the risk estimates of non-cancer effects from dermal
exposures do not support an unreasonable risk determination. When assuming the use of gloves
with PF of 5, the risk estimates of cancer from dermal exposures at the high-end do not support an
unreasonable risk determination. Gloves with PF of 5 are the assumed worker protection at
facilities using 1-BP in adhesives and sealants, based on professional judgement regarding
practices at such facilities.
Page 337 of 486
-------
• Inhalation exposures for workers (sprayers and non-sprayers) and ONUs were assessed using
personal breathing zone monitoring data collected from several studies, and EPA also considered
model data which indicated similar risks.
• Dermal exposures were assessed using modeled data.
In summary, the risk estimates, the health effects of 1-BP, the exposures, and consideration of
uncertainties support EPA's determination that there is unreasonable risk of injury to health (workers and
ONUs) from industrial and commercial use of 1-BP in adhesives and sealants.
5.2.1.14 Industrial/Commercial Use - Cleaning and furniture care products -
Dry cleaning solvent, spot cleaner and stain remover
Section 6(b)(4)(A) unreasonable risk determination for the industrial and commercial use of 1-BP in
cleaning and furniture care products in dry cleaning solvents, spot cleaners and stain removers: Presents
an unreasonable risk of injury to health (workers and ONUs).
For workers, EPA found there was unreasonable risk of non-cancer effects (developmental) from
acute and chronic inhalation exposures at the central tendency and high-end and of cancer from
chronic inhalation exposures at the central tendency and high-end, without assuming use of
respirators. In addition, for workers, EPA found there was unreasonable risk of cancer from
chronic dermal exposures at the high-end, without assuming use of gloves. For ONUs, EPA found
there was unreasonable risk of non-cancer effects (developmental) from acute and chronic
inhalation exposures at the central tendency and high-end and cancer from chronic inhalation
exposures at the central tendency and high-end.
EPA's determination that the industrial and commercial use of 1-BP in dry cleaning solvents, spot cleaners
and stain removers presents an unreasonable risk is based on the comparison of the risk estimates for non-
cancer effects and cancer to the benchmarks (Table 4-58) and other considerations. As explained in
Section 5.1, EPA considered the health effects of 1-BP, the exposures for the condition of use, and the
uncertainties in the analysis (Section 4.3):
• EPA does not assume workers to use any type of respirator or gloves during industrial and
commercial use of 1-BP at dry cleaning facilities.
• The workers considered included those operating the dry-cleaning machines (adding make-up
solvent, opening the machine door during the wash cycle, and removing loads from the machines)
and workers doing spot cleaning of garments.
• For workers, the risk estimates of non-cancer effects from dermal exposures do not support an
unreasonable risk determination.
• Inhalation exposures from dry cleaning solvent were assessed using personal breathing zone
monitoring data from three different studies of facilities using converted third generation machines.
A model was also used to represent exposures for larger facilities that may have multiple machines
and machine types, that indicated similar risks.
• Inhalation exposures for workers and ONUs for spot cleaners and stain removers were assessed
using personal breathing zone monitoring from OSHA inspections, which are not intended to
Page 338 of 486
-------
represent typical exposure levels at the workplace. The monitoring data was supplemented with a
model, and while there is uncertainty in the representativeness of the spot cleaner use rate, the
model results are in good agreement with the monitoring data.
• The modeled exposure concentrations for children (as shown in Table 2-22) are lower than those
for adult ONUs. Chronic scenarios were not calculated due to uncertainty in the exposure
frequency and number of years of exposure for children. In addition, it is unclear whether children
are present at any of the remaining eight dry cleaners.
• Dermal exposures were assessed using modeled data.
In summary, the risk estimates, the health effects of 1-BP, the exposures, and consideration of
uncertainties support EPA's determination that there is unreasonable risk of injury to health (workers and
ONUs) from industrial and commercial use of 1-BP in dry cleaning solvents, spot cleaners and stain
removers.
5.2.1.15 Industrial/Commercial Use - Cleaning and furniture care products -
Liquid cleaner (e.gcoin and scissor cleaner); liquid spray/aerosol cleaner
Section 6(b)(4)(A) unreasonable risk determination for industrial and commercial use of 1-BP in cleaning
and furniture care products in liquid cleaners (e.g., coin and scissor cleaner) and liquid spray/aerosol
cleaners: Presents an unreasonable risk of injury to health (workers and ONUs).
For workers, EPA found there was unreasonable risk of non-cancer effects (developmental) from
acute and chronic inhalation exposures at the central tendency and high-end, and of cancer from
chronic inhalation exposures at the central tendency and high-end, without assuming use of
respirators. For ONUs, EPA found there was unreasonable risk of non-cancer effects
(developmental) from acute and chronic inhalation exposures at the central tendency and high-end,
and of cancer from chronic inhalation exposures at the central tendency and high-end.
EPA's determination that the industrial and commercial use of 1-BP in liquid cleaners (e.g., coin and
scissor cleaner) and liquid spray/aerosol cleaners presents an unreasonable risk is based on comparison of
the risk estimates for non-cancer effects and cancer to the benchmarks (Table 4-58) and other
considerations. As explained in Section 5.1, EPA considered the health effects of 1-BP, the exposures for
the condition of use, and the uncertainties in the analysis (Section 4.3):
• EPA does not assume workers to use any type of respirator during industrial and commercial use of
1-BP in liquid cleaners (e.g., coin and scissor cleaner) and liquid spray/aerosol cleaners.
• For workers, the risk estimates of non-cancer effects from dermal exposures do not support an
unreasonable risk determination. When assuming the use of gloves with PF of 5, the risk estimates
of cancer from dermal exposures at the high-end do not support an unreasonable risk
determination. Gloves with PF of 5 are the assumed worker protection at facilities using 1-BP in
liquid cleaners and liquid spray/aerosol cleaners, based on professional judgement regarding
practices at such facilities.
• Inhalation and dermal exposures from industrial and commercial use of 1-BP in liquid cleaners
(e.g., coin and scissor cleaner) and liquid spray/aerosol cleaners were considered similar to the
Page 339 of 486
-------
exposures from the use of 1-BP in aerosol degreasing and the same risk estimates were considered
for this risk determination.
In summary, the risk estimates, the health effects of 1-BP, the exposures, and consideration of
uncertainties support EPA's determination that there is unreasonable risk of injury to health (workers and
ONUs) from other industrial and commercial use of 1-BP in liquid cleaners (e.g., coin and scissor cleaner)
and liquid spray/aerosol cleaners.
5.2.1.16 Other Industrial/Commercial Use - Arts, crafts, and hobby materials
(adhesive accelerant); automotive care products (engine degreaser, brake cleaner);
anti-adhesive agents (mold cleaning and release product); electronic and electronic
products and metal products; functional fluids - closed systems (refrigerant) and
open-systems (cutting oils); asphalt extraction; laboratory chemicals; and
temperature indicator (coatings)
Section 6(b)(4)(A) unreasonable risk determination for other industrial and commercial use of 1-BP in
arts, crafts, hobby materials (adhesive accelerant); automotive care products (engine degreaser. brake
cleaner); anti-adhesive agents (mold cleaning and release product); electronic and electronic products and
metal products; functional fluids - closed systems (refrigerant) and open-systems (cutting oils); asphalt
extraction; laboratory chemicals; and temperature indicator (coatings): Presents an unreasonable risk of
injury to health (workers and ONUs).
For workers, EPA found there was unreasonable risk of non-cancer effects (developmental) from
acute and chronic inhalation exposures at the central tendency and high-end, and of cancer from
chronic inhalation exposures at the central tendency and high-end, without assuming use of
respirators. For ONUs, EPA found there was unreasonable risk of non-cancer effects
(developmental) from acute and chronic inhalation exposures at the central tendency and high-end,
and of cancer from chronic inhalation exposures at the central tendency and high-end.
EPA's determination that the industrial and commercial use of 1-BP in other industrial and commercial
uses presents an unreasonable risk is based on the comparison of the risk estimates for non-cancer effects
and cancer to the benchmarks (Table 4-58) and other considerations. As explained in Section 5.1, EPA
considered the health effects of 1-BP, the exposures for the condition of use, and the uncertainties in the
analysis (Section 4.3):
• EPA does not assume workers to use any type of respirator during other industrial and commercial
uses of 1-BP.
• For workers, the risk estimates of non-cancer effects from dermal exposures do not support an
unreasonable risk determination. When assuming the use of gloves with PF of 5, the risk estimates
of cancer from dermal exposures at the high-end do not support an unreasonable risk
determination. Gloves with PF of 5 are the assumed worker protection at facilities using 1-BP in
other industrial and commercial uses, based on professional judgement regarding practices at such
facilities.
Page 340 of 486
-------
• Inhalation and dermal exposures from other industrial and commercial uses for 1-BP were
considered similar to the exposures from the use of 1-BP in aerosol degreasing and the same risk
estimates were considered for this risk determination.
In summary, the risk estimates, the health effects of 1-BP, the exposures, and consideration of
uncertainties support EPA's determination that there is unreasonable risk of injury to health (workers and
ONUs) from other industrial and commercial use of 1-BP in arts, crafts, hobby materials (adhesive
accelerant); automotive care products (engine degreaser, brake cleaner); anti-adhesive agents (mold
cleaning and release product); electronic and electronic products and metal products; functional fluids -
closed systems (refrigerant) and open-systems (cutting oils); asphalt extraction; laboratory chemicals; and
temperature indicator (coatings).
5.2.1.17 Consumer Use - Solvent (cleaning or degreasing) - Aerosol spray
degreasers/cleaners
Section 6(b)(4)(A) unreasonable risk determination for the consumer use of 1-BP as solvent in aerosol
spray degreasers/cleaners: Presents an unreasonable risk of injury to health (consumers and
bystanders).
For consumers, EPA found there was unreasonable risk of non-cancer effects (developmental) from
acute inhalation exposures at the low, moderate, and high intensity use. In addition, for consumers,
EPA found there was unreasonable risk of non-cancer effects (developmental) from acute dermal
exposures at the moderate and high intensity use. For bystanders, EPA found there was
unreasonable risk of non-cancer effects (developmental) from acute inhalation exposures at the low,
moderate and high intensity use.
EPA's determination that the consumer use of 1-BP as solvent in aerosol spray degreasers/cleaners
presents an unreasonable risk is based on the comparison of the risk estimates for non-cancer effects to the
benchmarks (Table 4-59) and other considerations. As explained in Section 5.1, EPA considered the health
effects of 1-BP, the exposures for the condition of use, and the uncertainties in the analysis (Section 4.3):
• Risk estimates for the consumer use of 1-BP as solvent in aerosol spray degreasers/cleaners was
based on modeled risk estimates of two products: aerosol spray degreaser/cleaner-general, aerosol
spray degreaser/cleaner-electronics.
• Inhalation exposures to consumers and bystanders were evaluated with the Consumer Exposure
Model (CEM). The magnitude of inhalation exposures to consumers and bystanders depends on
several factors, including the concentration of 1-BP in products used, use patterns (including
frequency, duration, amount of product used, room of use, and local ventilation), and application
methods.
• Dermal exposures to consumers were evaluated for one product with the CEM (Permeability) and
for the other product with the CEM (Fraction Absorbed). Dermal exposures to consumers result
from direct contact with the product or from vapor or mist deposition onto the skin while using the
product (dermal permeation). The magnitude of dermal exposures depends on several factors,
including skin surface area, product volume, concentration of 1-BP in product used, and dermal
Page 341 of 486
-------
exposure duration. The potential for dermal exposures to 1-BP is limited by several factors
including physical-chemical properties of 1-BP, high vapor pressure, and quick volatilization of
product containing 1-BP from surfaces.
In summary, the risk estimates, the health effects of 1-BP, the exposures, and consideration of
uncertainties support EPA's determination that there is unreasonable risk of injury to health (consumers
and bystanders) from the consumer use of 1-BP as solvent in aerosol spray degreasers/cleaners.
5.2.1.18 Consumer Use - Cleaning and furniture care products - Spot cleaner
and stain remover (Spot cleaners and stain removers)
Section 6(b)(4)(A) unreasonable risk determination for the consumer use of 1-BP in spot cleaners and
stain removers: Presents an unreasonable risk of injury to health (consumers and bystanders).
For consumers, EPA found there was unreasonable risk of non-cancer effects (developmental) from
acute inhalation exposures at the low, moderate, and high intensity use. In addition, for consumers,
EPA found there was unreasonable risk of non-cancer effects (developmental) from acute dermal
exposures at the high intensity use. For bystanders, EPA found there was unreasonable risk of non-
cancer effects (developmental) from acute inhalation exposures at the moderate and high intensity
use.
EPA's determination that the consumer uses of 1-BP in spot cleaners and stain removers presents an
unreasonable risk is based on the comparison of the risk estimates for non-cancer effects to the
benchmarks (Table 4-59) and other considerations. As explained in Section 5.1, EPA considered the health
effects of 1-BP, the exposures for the condition of use, and the uncertainties in the analysis (Section 4.3):
• Inhalation exposures to consumers and bystanders were evaluated with the Consumer Exposure
Model (CEM). The magnitude of inhalation exposures to consumers and bystanders depends on
several factors, including the concentration of 1-BP in products used, use patterns (including
frequency, duration, amount of product used, room of use, and local ventilation), and application
methods.
• Dermal exposures to consumers were evaluated with the CEM (Permeability). Dermal exposures to
consumers result from direct contact with the product or from vapor or mist deposition onto the
skin while using the product (dermal permeation). The magnitude of dermal exposures depends on
several factors, including skin surface area, product volume, concentration of 1-BP in product
used, and dermal exposure duration. The potential for dermal exposures to 1-BP is limited by
several factors including physical-chemical properties of 1-BP, high vapor pressure, and quick
volatilization of product containing 1-BP from surfaces.
In summary, the risk estimates, the health effects of 1-BP, the exposures, and consideration of
uncertainties support EPA's determination that there is unreasonable risk of injury to health (consumers
and bystanders) from the consumer use of 1-BP in spot cleaners and stain removers.
Page 342 of 486
-------
5.2.1.19 Consumer Use - Cleaning and furniture care products - Liquid cleaner
(e.gcoin and scissor cleaner)
Section 6(b)(4)(A) unreasonable risk determination for the consumer use of 1-BP in liquid cleaner (e.g.,
coin and scissor cleaner): Presents an unreasonable risk of injury to health (consumers and
bystanders).
For consumers and bystanders, EPA found there was unreasonable risk of non-cancer effects
(developmental) from acute inhalation exposures at the low, moderate and high intensity use.
EPA's determination that the consumer uses of 1-BP in liquid cleaner (e.g., coin and scissor cleaner)
presents an unreasonable risk is based on the comparison of the risk estimates for non-cancer effects to the
benchmarks (Table 4-59) and other considerations. As explained in Section 5.1, EPA considered the health
effects of 1-BP, the exposures for the condition of use, and the uncertainties in the analysis (Section 4.3):
• For consumers, the risk estimates of non-cancer effects from acute dermal exposures do not
support an unreasonable risk determination.
• Inhalation exposures to consumers and bystanders were evaluated with the Multi-Chamber
Concentration and Exposure Model (MCCEM). The magnitude of inhalation exposures to
consumers and bystanders depends on several factors, including the concentration of 1-BP in
products used, use patterns (including frequency, duration, amount of product used, room of use,
and local ventilation), and application methods.
• Dermal exposures to consumers were evaluated with the CEM (Permeability). Dermal exposures to
consumers result from direct contact with the product or from vapor or mist deposition onto the
skin while using the product (dermal permeation). The magnitude of dermal exposures depends on
several factors, including skin surface area, product volume, concentration of 1-BP in product
used, and dermal exposure duration. The potential for dermal exposures to 1-BP is limited by
several factors including physical-chemical properties of 1-BP, high vapor pressure, and quick
volatilization of product containing 1-BP from surfaces.
In summary, the risk estimates, the health effects of 1-BP, the exposures, and consideration of
uncertainties support EPA's determination that there is unreasonable risk of injury to health (consumers
and bystanders) from the consumer use of 1-BP in liquid cleaner (e.g., coin and scissor cleaner).
5.2.1.20 Consumer Use - Cleaning and furniture care products - Liquid
spray/aerosol cleaner
Section 6(b)(4)(A) unreasonable risk determination for the consumer use of 1-BP in liquid spray/aerosol
cleaners: Presents an unreasonable risk of injury to health (consumers and bystanders).
For consumers, EPA found there was unreasonable risk of non-cancer effects (developmental) from
acute inhalation exposures at the low, moderate, and high intensity use. In addition, for consumers,
EPA found there was unreasonable risk of non-cancer effects (developmental) from acute dermal
exposures at the moderate and high intensity use. For bystanders, EPA found there was
Page 343 of 486
-------
unreasonable risk of non-cancer effects (developmental) from acute inhalation exposures at the low,
moderate and high intensity use.
EPA's determination that the consumer uses of 1-BP in liquid spray/aerosol cleaners presents an
unreasonable risk is based on the comparison of the risk estimates for non-cancer effects to the
benchmarks (Table 4-59) and other considerations. As explained in Section 5.1, EPA considered the health
effects of 1-BP, the exposures for the condition of use, and the uncertainties in the analysis (Section 4.3):
• Risk estimates for the consumer use of 1-BP in liquid spray/aerosol cleaners were based on
modeled risk estimates of one product: spray cleaner-general.
• Inhalation exposures to consumers and bystanders were evaluated with the Consumer Exposure
Model (CEM). The magnitude of inhalation exposures to consumers and bystanders depends on
several factors, including the concentration of 1-BP in products used, use patterns (including
frequency, duration, amount of product used, room of use, and local ventilation), and application
methods.
• Dermal exposures to consumers were evaluated with the CEM (Permeability). Dermal exposures to
consumers result from direct contact with the product or from vapor or mist deposition onto the
skin while using the product (dermal permeation). The magnitude of dermal exposures depends on
several factors, including skin surface area, product volume, concentration of 1-BP in product
used, and dermal exposure duration. The potential for dermal exposures to 1-BP is limited by
several factors including physical-chemical properties of 1-BP, high vapor pressure, and quick
volatilization of product containing 1-BP from surfaces.
In summary, the risk estimates, the health effects of 1-BP, the exposures, and consideration of
uncertainties support EPA's determination that there is unreasonable risk of injury to health (consumers
and bystanders) from the consumer use of 1-BP in liquid spray/aerosol cleaners.
5.2.1.21 Consumer Use - Other uses - Arts, crafts and hobby materials
(adhesive accelerant)
Section 6(b)(4)(A) unreasonable risk determination for the consumer use of 1-BP in arts, crafts, hobby
materials (adhesive accelerant): Presents an unreasonable risk of injury to health (consumers and
bystanders).
For consumers, EPA found there was unreasonable risk of non-cancer effects (developmental) from
acute inhalation exposures at the low, moderate, and high intensity use. For bystanders, EPA found
there was unreasonable risk of non-cancer effects (developmental) from acute inhalation exposures
at the moderate and high intensity use.
EPA's determination that the consumer uses of 1-BP in arts, crafts, hobby materials (adhesive accelerant)
presents an unreasonable risk is based on the comparison of the risk estimates for non-cancer effects to the
benchmarks (Table 4-59) and other considerations. As explained in Section 5.1, EPA considered the health
effects of 1-BP, the exposures for the condition of use, and the uncertainties in the analysis (Section 4.3):
Page 344 of 486
-------
• Inhalation exposures to consumers and bystanders were evaluated with the Consumer Exposure
Model (CEM). The magnitude of inhalation exposures to consumers and bystanders depends on
several factors, including the concentration of 1-BP in products used, use patterns (including
frequency, duration, amount of product used, room of use, and local ventilation), and application
methods.
• Dermal exposures to consumers were evaluated with the CEM (Fraction Absorbed). Dermal
exposures to consumers result from direct contact with the product or from vapor or mist
deposition onto the skin while using the product (dermal permeation). The magnitude of dermal
exposures depends on several factors, including skin surface area, product volume, concentration
of 1-BP in product used, and dermal exposure duration. The potential for dermal exposures to 1-BP
is limited by several factors including physical-chemical properties of 1-BP, high vapor pressure,
and quick volatilization of product containing 1-BP from surfaces.
In summary, the risk estimates, the health effects of 1-BP, the exposures, and consideration of
uncertainties support EPA's determination that there is unreasonable risk of injury to health (consumers
and bystanders) from the consumer use of 1-BP in arts, crafts, hobby materials (adhesive accelerant).
5.2.1.22 Consumer Use - Other uses - Automotive care products (refrigerant
flush)
Section 6(b)(4)(A) unreasonable risk determination for the consumer use of 1-BP in automotive care
products (refrigerant flush): Presents an unreasonable risk of injury to health (consumers and
bystanders).
For consumers, EPA found there was unreasonable risk of non-cancer effects (developmental) from
acute inhalation and dermal exposures at the low, moderate, and high intensity use. For bystanders,
EPA found there was unreasonable risk of non-cancer effects (developmental) from acute inhalation
exposures at the low, moderate and high intensity use.
EPA's determination that the consumer uses of 1-BP in automotive care products (refrigerant flush)
presents an unreasonable risk is based on the comparison of the risk estimates for non-cancer effects to the
benchmarks (Table 4-59) and other considerations. As explained in Section 5.1, EPA considered the health
effects of 1-BP, the exposures for the condition of use, and the uncertainties in the analysis (Section 4.3):
• Inhalation exposures to consumers and bystanders were evaluated with the Multi-Chamber
Concentration and Exposure Model (MCCEM). The magnitude of inhalation exposures to
consumers and bystanders depends on several factors, including the concentration of 1-BP in
products used, use patterns (including frequency, duration, amount of product used, room of use,
and local ventilation), and application methods.
• Dermal exposures to consumers were evaluated with the CEM (Fraction Absorbed). Dermal
exposures to consumers result from direct contact with the product or from vapor or mist
deposition onto the skin while using the product (dermal permeation). The magnitude of dermal
exposures depends on several factors, including skin surface area, product volume, concentration
of 1-BP in product used, and dermal exposure duration. The potential for dermal exposures to 1-BP
Page 345 of 486
-------
is limited by several factors including physical-chemical properties of 1-BP, high vapor pressure,
and quick volatilization of product containing 1-BP from surfaces.
In summary, the risk estimates, the health effects of 1-BP, the exposures, and consideration of
uncertainties support EPA's determination that there is unreasonable risk of injury to health (consumers
and bystanders) from the consumer use of 1-BP in automotive care products (refrigerant flush).
5.2.1.23 Consumer Use - Other uses - Anti-adhesive agents (mold cleaning and
release product)
Section 6(b)(4)(A) unreasonable risk determination for the consumer use of 1-BP in anti-adhesive agents
(mold cleaning and release product): Presents an unreasonable risk of injury to health (consumers and
bystanders).
For consumers, EPA found there was unreasonable risk of non-cancer effects (developmental) from
acute inhalation exposures at the low, moderate and high intensity use. For bystanders, EPA found
there was unreasonable risk of non-cancer effects (developmental) from acute inhalation exposures
at the moderate and high intensity use.
EPA's determination that the consumer uses of 1-BP in anti-adhesive agents (mold cleaning and release
product) presents an unreasonable risk is based on the comparison of the risk estimates for non-cancer
effects to the benchmarks (Table 4-59) and other considerations. As explained in Section 5.1, EPA
considered the health effects of 1-BP, the exposures for the condition of use, and the uncertainties in the
analysis (Section 4.3):
• Inhalation exposures to consumers and bystanders were evaluated with the Consumer Exposure
Model (CEM). The magnitude of inhalation exposures to consumers and bystanders depends on
several factors, including the concentration of 1-BP in products used, use patterns (including
frequency, duration, amount of product used, room of use, and local ventilation), and application
methods.
• Dermal exposures to consumers were evaluated with the CEM (Fraction Absorbed). Dermal
exposures to consumers result from direct contact with the product or from vapor or mist
deposition onto the skin while using the product (dermal permeation). The magnitude of dermal
exposures depends on several factors, including skin surface area, product volume, concentration
of 1-BP in product used, and dermal exposure duration. The potential for dermal exposures to 1-BP
is limited by several factors including physical-chemical properties of 1-BP, high vapor pressure,
and quick volatilization of product containing 1-BP from surfaces.
In summary, the risk estimates, the health effects of 1-BP, the exposures, and consideration of
uncertainties support EPA's determination that there is unreasonable risk of injury to health (consumers
and bystanders) from the consumer use of 1-BP in anti-adhesive agents (mold cleaning and release
product).
Page 346 of 486
-------
5.2.1.24 Commercial and Consumer Use - Insulation (building/construction
materials not covered elsewhere)
Section 6(b)(4)(A) unreasonable risk determination for the use of 1-BP in insulation: Does not present an
unreasonable risk of injury to health (workers, ONUs, consumers, and bystanders).
For workers, EPA found that there was no unreasonable risk of non-cancer effects (developmental) from
acute and chronic inhalation and dermal exposures at the central tendency and high-end, and of cancer
from chronic inhalation and dermal exposures at the central tendency and high-end, without assuming use
of PPE. For ONUs, EPA found that there was no unreasonable risk of non-cancer effects (developmental)
from acute and chronic inhalation exposures at the central tendency or high-end, and of cancer from
chronic inhalation exposures at the central tendency or high-end. For consumers, EPA found that there
was no unreasonable risk of non-cancer effects (developmental) from acute inhalation and dermal
exposures at the low, moderate or high intensity use. For bystanders EPA found that there was no
unreasonable risk of non-cancer effects (developmental) from acute inhalation exposures at the low,
moderate or high intensity use. For consumers and bystanders, EPA found that there was no an
unreasonable risk of non-cancer effects (developmental) and cancer from chronic inhalation exposures.
EPA's determination that the use of 1-BP in insulation does not present an unreasonable risk is based on
the comparison of the risk estimates for non-cancer effects and cancer to the benchmarks (Table 4-58 and
Table 4-59) and other considerations. As explained in Section 5.1, EPA considered the health effects of 1-
BP, the exposures from the condition of use, and the uncertainties in the analysis (Section 4.3):
• EPA conducted a screening-level analysis using EPA's Indoor Environment Concentrations in
Buildings with Conditioned and Unconditioned Zones (IECCU) model to estimate the potential 1-
BP concentration from off-gassing of insulation.
• For workers and ONUs, exposures to 1-BP during installation is negligible since 1-BP
concentrations are below 0.01 ppm 8-hr TWA inside a residential home for the initial work day,
and less on subsequent days after installation.
• For consumers and bystanders, two building configurations were evaluated encompassing attic,
living space, crawlspace and basement. Also, the evaluation encompassed both acute and chronic
exposures to account for the off-gassing of the installed board that may be ongoing for months.
In summary, the risk estimates, the health effects of 1-BP, the exposures, and consideration of
uncertainties support EPA's determination that there is no unreasonable risk of injury to health (workers,
ONUs, consumers and bystanders) from the use of 1-BP in insulation.
5.2.1.25 Disposal - Disposal - municipal waste incinerator, off-site waste
transfer (Disposal)
Section 6(b)(4)(A) unreasonable risk determination for the disposal of 1-BP: Does not present an
unreasonable risk of injury to health (workers and ONUs).
For workers, EPA found that there was no unreasonable risk of non-cancer effects (developmental) from
acute and chronic inhalation or dermal exposures at the central tendency and high-end, even when PPE is
Page 347 of 486
-------
not used. In addition, for workers, EPA found that there was no unreasonable risk of cancer from chronic
inhalation or dermal exposures at the central tendency or high-end, when assuming use of PPE. For ONUs,
EPA found that there was no unreasonable risk of non-cancer effects (developmental) from acute and
chronic inhalation exposures or of cancer from chronic inhalation exposures.
EPA's determination that the disposal of 1-BP does not present an unreasonable risk is based on the
comparison of the risk estimates for non-cancer effects and cancer to the benchmarks (Table 4-58) and
other considerations. As explained in Section 5.1, EPA considered the health effects of 1-BP, the
exposures for the condition of use, and the uncertainties in the analysis (Section 4.3), including
uncertainties related to the exposures for ONUs:
• For workers, when assuming the use of respirators with APF of 10 and gloves with PF of 5, the
risk estimates of cancer from chronic inhalation and dermal exposures at the high-end do not
support an unreasonable risk determination. Respirators with APF of 10 and gloves with PF of 5
are the assumed personal protective equipment for workers at disposal facilities, based on
professional judgement regarding likely practices at a processing facility.
• Inhalation exposures were assessed using modeled data. The model is representative of exposure
associated with bulk container loading; however, the model does not account for other potential
sources of exposure at disposal facilities, such as equipment cleaning.
• The uncertainties also include the inhalation exposures for ONUs, which are assumed to be
negligible due to the dilution of 1-BP into the ambient air in the model used.
• Dermal exposures were also assessed using modeled data.
In summary, the risk estimates, the health effects of 1-BP, the exposures, and consideration of
uncertainties support EPA's determination that there is no unreasonable risk of injury to health (workers
and ONUs) from the disposal of 1-BP.
5.2.1.26 General Population
Section 6(b)(4)(A) unreasonable risk determination for all conditions of use of 1-BP: Does not present an
unreasonable risk of injury to health (general population). For all conditions of use, EPA found that there
were no exposures from drinking water, surface water and sediment. EPA considered reasonably available
information and environmental fate properties to characterize general population exposure. EPA does not
expect general population exposure from the ingestion of contaminated drinking water. EPA did not
evaluate risks to the general population from ambient air and disposal pathways for any conditions of use,
and the unreasonable risk determinations do not account for exposures to the general population from
ambient air and disposal pathways.
5.2.2 Environment
Section 6(b)(4)(A) unreasonable risk determination for all conditions of use of 1-BP: Does not present an
unreasonable risk of injury to the environment (aquatic, sediment dwelling and terrestrial organisms).
Page 348 of 486
-------
For all conditions of use, EPA found that there were no exceedances of benchmarks to aquatic organisms
from exposures to 1-BP. The RQ values associated with acute and chronic exposures are <0.01 and 0.12,
respectively, based on the best available science (Table 4-2). While one single study was used to
characterize the environmental hazards, it was of high quality, based on EPA's systematic review, and the
analysis was complemented with modeling. The experimental procedures used in this effort represent the
best practices for conducting acute toxicity testing with fathead minnows and are consistent with the test
guidelines currently recommended by EPA and international regulatory partner organizations for
conducting ecological risk assessment purposes for fish. The confidence in the available data to
characterize the environmental hazards of 1-BP is bolstered by the use of the QSAR modeling program
ECOSAR (v2.0) (EPA. 2017) lending greater confidence to the risk estimates.
The high volatility, high water solubility and low Log Koc of 1-BP suggest that 1-BP will only be present
at low concentrations in the sediment and terrestrial environmental compartments.
In summary, the risk estimates, the environmental effects of 1-BP, the exposures, physical-chemical
properties of 1-BP and consideration of uncertainties support EPA's determination that there is no
unreasonable risk to the environment from all conditions of use of 1-BP.
5.3 Changes to the Unreasonable Risk Determination from Draft Risk
Evaluation to Final Risk Evaluation
EPA uses representative Occupational Exposure Scenarios and Consumer Exposure Scenarios to generate
risk estimates. Sometimes the same Exposure Scenario is used for several conditions of use, and
sometimes unreasonable risk determinations are based on multiple exposure scenarios. EPA makes an
unreasonable risk determination for each condition of use within the scope of the risk evaluation. In the
draft risk evaluation, EPA evaluated the commercial uses of 1-BP in insulation as part of the other
industrial and commercial uses of 1-BP; however, the Occupational Exposure Scenario used for the other
industrial and commercial uses of 1-BP was not adequate to evaluate the installation of insulation
containing 1-BP. EPA has developed an occupational scenario for the commercial use of 1-BP in
insulation and therefore such use has a different unreasonable risk determination in this final risk
evaluation. In addition, for further clarity, EPA is now issuing a single unreasonable risk determination for
dry cleaning solvent and spot cleaner, stain remover. EPA is also issuing an unreasonable risk
determination for the liquid cleaner and liquid spray/aerosol cleaner that is separate from the unreasonable
risk determination for other industrial and commercial uses.
Page 349 of 486
-------
Table 5-2. Updates in Presentation of Unreasonable Risk Determinations Between Draft and
Final Risk Evaluations
I iiiviisoiiiihlo Risk IkMi'i'iiiiiiiilions in
l-'iiiiil Risk l-'\iilii;ili«ui
I mviisoiiiihk' Risk Doloriniiiiilions in Dml'i Risk l-'.\iiln;ilion
icmpkiMs nddcd)
• Industrial and commercial use
in cleaning and furniture care
products in liquid cleaners
(e.g., coin and scissor cleaner)
and liquid spray/aerosol
cleaners
• Industrial and commercial use as a cleaning and
furniture care product in the form of liquid cleaner
(e.gcoin and scissor cleaner) and liquid spray or
aerosol cleaner as well as other industrial and
commercial uses: arts, crafts, hobby materials (adhesive
accelerant); automotive care products (engine
degreaser, brake cleaner, refrigerant flush); anti-
adhesive agents (mold cleaning and release product);
building/construction materials not covered
elsewhere (insulation); electronic and electronic
products and metal products; functional fluids
(close/open-systems) - refrigerant/cutting oils; asphalt
extraction; laboratory chemicals; and temperature
indicator - coatings
• Commercial and consumer
uses of building/construction
materials (insulation)
• Other industrial and
commercial use in arts, crafts,
hobby materials (adhesive
accelerant); automotive care
products (engine degreaser,
brake cleaner); anti-adhesive
agents (mold cleaning and
release product); electronic and
electronic products and metal
products; functional fluids -
closed systems (refrigerant)
and open-systems (cutting
oils); asphalt extraction;
laboratory chemicals; and
temperature indicator
(coatings)
• Industrial and commercial use
as cleaning and furniture care
products in dry cleaning
solvents, spot cleaners and
stain removers
• Industrial and commercial use as cleaning and furniture
care products in dry cleaning solvents
• Industrial and commercial use as cleaning and furniture
care products in the form of spot cleaner and stain
remover
Page 350 of 486
-------
5.4 Unreasonable Risk Determination Conclusion
5.4,1 No Unreasonable Risk Determinations
TSCA section 6(b)(4) requires EPA to conduct risk evaluations to determine whether chemical
substances present unreasonable risk under their conditions of use. In conducting risk evaluations,
"EPA will determine whether the chemical substance presents an unreasonable risk of injury to
health or the environment under each condition of use within the scope of the risk evaluation..." 40
CFR 702.47. Pursuant to TSCA section 6(i)(l), a determination of "no unreasonable risk" shall be
issued by order and considered to be final agency action. Under EPA's implementing regulations,
"[a] determination made by EPA that the chemical substance, under one or more of the conditions
of use within the scope of the risk evaluations, does not present an unreasonable risk of injury to
health or the environment will be issued by order and considered to be a final Agency action,
effective on the date of issuance of the order." 40 CFR 702.49(d).
EPA has determined that the following conditions of use of 1-BP do not present an unreasonable risk of
injury to health or the environment:
• Manufacturing: domestic manufacturing (Section 5.2.1.1, Section 5.2.1.26, Section 5.2.2,
Section 4, Section 3, and Section 2.3.1.5)
• Manufacturing: import (Section 5.2.1.2, Section 5.2.1.26, Section 5.2.2, Section 4, Section
3, and Section 2.3.1.6)
• Processing: as a reactant (Section 5.2.1.3, Section 5.2.1.26, Section 5.2.2, Section 4,
Section 3, and Section 2.3.1.7)
• Processing: incorporation into articles (Section 5.2.1.5, Section 5.2.1.26, Section 5.2.2,
Section 4, Section 3, and Section 2.3.1.9)
• Processing: repackaging (Section 5.2.1.6, Section 5.2.1.26, Section 5.2.2, Section 4, Section
3, and Section 2.3.1.10)
• Processing: recycling (Section 5.2.1.7, Section 5.2.1.26, Section 5.2.2, Section 4, Section 3,
and Section 2.3.1.21)
• Distribution in commerce (Section 5.2.1.8, Section 5.2.1.26, Section 5.2.2, Section 4, and
Section 3)
• Commercial and consumer uses of building/construction materials (insulation) (Section
5.2.1.24, Section 5.2.1.26, Section 5.2.2, Section 4, Section 3, and Section 2.3.1.19)
• Disposal (Section 5.2.1.25, Section 5.2.1.26, Section 5.2.2, Section 4, Section 3, and
Section 2.3.1.21)
This subsection of the final risk evaluation therefore constitutes the order required under TSCA
section 6(i)(l), and the "no unreasonable risk" determinations in this subsection are considered to
be final agency action effective on the date of issuance of this order. All assumptions that went into
reaching the determinations of no unreasonable risk for these conditions of use, including any
considerations excluded for these conditions of use, are incorporated into this order.
Page 351 of 486
-------
The support for each determination of "no unreasonable risk" is set forth in Section 5.2 of the final
risk evaluation, "Detailed Unreasonable Risk Determinations by Condition of Use." This
subsection also constitutes the statement of basis and purpose required by TSCA section 26(f).
5.4,2 Unreasonable Risk Determinations
EPA has determined that the following conditions of use of 1-BP present an unreasonable risk of injury:
• Processing: incorporation into formulation, mixture, or reaction products
• Industrial and commercial use as solvent for cleaning and degreasing in vapor degreaser
(batch vapor degreaser - open-top, inline vapor degreaser)
• Industrial and commercial use as solvent for cleaning and degreasing in vapor degreaser
(batch vapor degreaser - closed-loop)
• Industrial and commercial use as solvent for cleaning and degreasing in cold cleaners
• Industrial and commercial use as solvent in aerosol spray degreaser/cleaner
• Industrial and commercial use in adhesives and sealants
• Industrial and commercial use in dry cleaning solvents, spot cleaners and stain removers
• Industrial and commercial use in liquid cleaners (e.g., coin and scissor cleaner) and liquid
spray/aerosol cleaners
• Other industrial and commercial uses: arts, crafts, hobby materials (adhesive accelerant);
automotive care products (engine degreaser, brake cleaner, refrigerant flush); anti-adhesive
agents (mold cleaning and release product); electronic and electronic products and metal
products; functional fluids (close/open-systems) - refrigerant/cutting oils; asphalt
extraction; laboratory chemicals; and temperature indicator - coatings
• Consumer use as solvent in aerosol spray degreasers/cleaners
• Consumer use in spot cleaners and stain removers
• Consumer use in liquid cleaner (e.g., coin and scissor cleaner)
• Consumer use in liquid spray/aerosol cleaners
• Consumer use in arts, crafts, hobby materials (adhesive accelerant)
• Consumer use in automotive care products (refrigerant flush)
• Consumer use in anti-adhesive agents (mold cleaning and release product)
EPA will initiate TSCA section 6(a) risk management actions on these conditions of use as
required under TSCA section 6(c)(1). Pursuant to TSCA section 6(i)(2), the "unreasonable risk"
determinations for these conditions of use are not considered final agency actions.
Page 352 of 486
-------
6 REFERENCES
Ahlers. J; Riedhammer. C; Vogliano. M; Ebert. RU; Kuhne. R; Schuunnann. G. (2006). Acute to
chronic ratios in aquatic toxicity—variation across trophic levels and relationship with
chemical structure. Environ Toxicol Chem 25: 2937-2945.
Ahlers. J; Riedhammer. C; Vogliano. M; Ebert. RU; Kuhne. R; Schuunnann. G. (2006). Acute to
chronic ratios in aquatic toxicity—variation across trophic levels and relationship with
chemical structure. Environ Toxicol Chem 25: 2937-2945.
AIA. (2017). Re: Posting EPA-HQ-OPPT-2016-0723 1-Bromopropane (n-Propyl bromide)
(CASRN 106-94-5). (EPA-HQ-OPPT-2016-0741-0014).
AIHA. (2009). Mathematical models for estimating occupational exposure to chemicals. In CB
Keil; CE Simmons; TR Anthony (Eds.), (2nd ed.). Fairfax, VA: AIHA Press.
Alwis. KU: Blount. BC: Britt. AS: Patel. D; Ashley. PL. (2012). Simultaneous analysis of 28
urinary VOC metabolites using ultra high performance liquid chromatography coupled with
electrospray ionization tandem mass spectrometry (UPLC-ESI/MSMS). Anal Chim Acta
750: 152-160. http://dx.doi.Org/10.1016/i.aca.2012.04.009
Ames. BN: McCann. J: Yamasaki. E. (1975). Methods for detecting carcinogens and mutagens
with the Salmonella/mammalian-microsome mutagenicity test. Mutat Res 31: 347-363.
Anderson. SE; Franko. J: Anderson. KL; Munson. AE; Lukomska. E; Meade. BJ. (2013).
Immunotoxicity and allergic potential induced by topical application of dimethyl carbonate
(DMC) in a murine model. J Immunotoxicol 10: 59-66.
http://dx.doi.org/10.3109/1547691X.2012.691124
Anderson. SE: Munson. AE: Butterworth. LF; Germolec. D; Morgan. PL: Roy croft. JA; Dill. J:
Meade. BJ. (2010). Whole-body inhalation exposure to 1-bromopropane suppresses the
IgM response to sheep red blood cells in female B6C3F1 mice and Fisher 344/N rats. Inhal
Toxicol 22: 125-132. http://dx.doi.org/10.3109/0895837090295391Q
Apfel. MA: Ikeda. BH; Speckhard. DC: Frev. PA. (1984). Escherichia coli Pyruvate
Dehydrogenase Complex. Thiamin Pyrophosphate-dependent Inactivation of 3-
bromopyruvate. J Biol Chem 259: 2905-2909.
Arakawa. S: Fuiimoto. K; Kato. A: Endo. S: Fukahori. A: Shinagawa. A: Fischer. T; Mueller. J:
Takasaki. W. (2012). Evaluation of hepatic glutathione transferase Mu 1 and Theta 1
activities in humans and mice using genotype information. Drug Metab Dispos 40: 497-
503. http://dx.doi.Org/10.l 124/dmd.l 11.042911
AT SDR. (2017). Toxicological profile forl-bromopropane. Atlanta, GA: Division of Toxicology
and Human Health Sciences, Environmental Toxicology Branch.
https://www.atsdr.cdc.gov/ToxProfiles/tp209.pdf
B Hymer. C: Cheever. KL. (2005). Development of a headspace gas chromatographic test for the
quantification of 1- and 2-bromopropane in human urine. J Chromatogr B Analyt Technol
Biomed Life Sci 814: 185-189. http://dx.doi.Org/10.1016/i.ichromb.2004.10.045
Baker. JP; Rabin. BR. (1969). Effects of Bromopyruvate on the control and catalytic properties of
Glutamate Dehydrogenase. 11:154-159. http://dx.doi.org/10.Ill 1/i. 1432-
1033.1969.tb00753.x
Page 353 of 486
-------
Baldwin. PE; Mavnard. AD. (1998). A Survey of Wind Speed in Indoor Workplaces. Ann Occup
Hyg 42: 303-313.
Banu. S; Ichihara. S; Huang. F; Ito. H; Inaguma. Y; Furuhashi. K; Fukunaga. Y; Wang. Q; Kitoh.
J; Ando. H; Kikkawa. F; Ichihara. G. (2007). Reversibility of the adverse effects of 1-
bromopropane exposure in rats. Toxicol Sci 100: 504-512.
http://dx.doi.org/10.1093/toxsci/kfm245
Barber. ED: Donish. WH: Mueller. KR. (1981). A procedure for the quantitative measurement of
the mutagenicity of volatile liquids in the Ames salmonella/microsome assay. Mutat Res
Genet Toxicol 90: 31-48. http://dx.doi.org/10.1016/0165-1218(8n90048-3
Barker. DJP. (2007). The origins of the developmental origins theory. J Intern Med 261: 412-417.
http://dx.doi.org/10.1111/i. 1365-2796.2007.01809.X
Barnslev. EA; Grenbv. TH; Young. L. (1966). Biological Studies of Toxic Agents. The
metabolism of 1- and 2-bromopropane. Biochem J 100: 282.
Barnthouse. LW: Munns. RM. Jr.: Sorensen. MT. (2008). Population-level ecological risk
assessment. Pensacola, FL: Taylor & Francis.
http://www.crcpress.com/product/isbn/9781420Q53326
Batterman. S: Jia. C: Hatzivasilis. G. (2007). Migration of volatile organic compounds from
attached garages to residences: A major exposure source. Environ Res 104: 224-240.
http://dx.doi.Org/10.1016/i.envres.2007.01.008
Belkin. S. (1992). BIODEGRADATION OF HALOALKANES. In International Workshop On
The Use Of Microorganisms To Combat Pollution, Israel, May (pp. 10-18). (ISSN 0923-
9820; EISSN 1572-9729; BIOSIS/93/26758). National Board of Labour Protection
(Finland). http://dx.doi.org/10.1007/BF0012909Q
Benigni. R; Bossa. C: Tcheremenskaia. O: Battistelli. CL; Crettaz. P. (2012). The new ISSMIC
database on in vivo micronucleus and its role in assessing genotoxicity testing strategies
[Review], Mutagenesis 27: 87-92. http://dx.doi.org/10.1093/mutage/ger064
BioReliance. (2015). Appendix III. Closed-System Ames Test on 1-Bromopropane Conducted at
BioReliance and Sponsored by Albemarle Corporation FINAL REPORT.
(AD58PU.503001.BTL).
Blando. J: Schill. D; De La Cruz. P; Zhang. L; Zhang. J. (2009). PERC ban among dry cleaners
leads to 1-bromopropane exposures with alternative "green" solvent. Presentation presented
at Fall Regulatory Update: New Jersey Department of Environmental Protection, October
16, 2009, Trenton, NJ.
Blando. JD; Schill. DP: De La Cruz. MP: Zhang. L; Zhang. J. (2010). Preliminary study of propyl
bromide exposure among New Jersey dry cleaners as a result of a pending ban on
perchloroethylene. J Air Waste Manag Assoc 60: 1049-1056.
http://dx.doi.Org/10.3155/1047-3289.60.9.1049
Boublik. T; Fried. V: Hala. E. (1984). The vapour pressures of pure substances: Selected values of
the temperature dependence of the vapour pressures of some pure substances in the normal
and low pressure region (2nd Revised ed.). Amsterdam, The Netherlands: Elsevier Science
Publishers.
Boyle. EB; Viet. SM; Wright. DJ: Merrill. LS: Alwis. KU; Blount. BC: Mortensen. ME: Move. J:
Dellarco. M. (2016). Assessment of Exposure to VOCs among Pregnant Women in the
Page 354 of 486
-------
National Children's Study. Int J Environ Res Public Health 13: 376.
http://dx.doi.org/10.3390/iierphl304Q376
Boysen. G: Pachkowski. BF; Nakamura. J: Swenberg. JA. (2009). The formation and biological
significance ofN7-guanine adducts [Review], MutatRes 678: 76-94.
http://dx.doi.Org/10.1016/i.mrgentox.2009.05.006
Bureau. USC. (2015). Statistics of U.S. Businesses (SUSB).
https://www.census.gov/data/tables/2015/econ/susb/2015-susb-annual.html
Burkholder. JB; Gilles. MK: Gierczak. T; Ravishankara. AR. (2002). The atmospheric degradation
of 1-bromopropane (CH3CH2CH2Br): The photochemistry of bromoacetone. Geophys Res
Lett 29: 1822. http://dx.doi.org/10.1029/2002GL014712
CARB. (2000). Initial statement of reasons for the proposed airborne toxic control measure for
emissions of chlorinated toxic air contaminants from automotive maintenance and repair
activities.
CARB. (2011). Development of updated ARB solvent cleaning emissions inventories. Final
Report: Agreement No. 06-322. In University of California, Riverside Bourns College of
Engineering, Center for Environmental Research and Technology. Sacramento, CA.
http://www.arb.ca.gov/research/apr/past/06-322.pdf
Casazza. JP; Felver. ME: Veech. RL. (1984). The metabolism of acetone in rat. J Biol Chem 259:
231-236.
(1997). Control of exposure to perchloroethylene in commercial dry cleaning (Mashine
Design). (DHHS(NIOSH) Publication No. 97-154). Atlanta, GA: Centers forDesease
Control and Prevention, http://www.cdc.gov/niosh/docs/hazardcontrol/hcl6.html
(2008). Neurologic illness associated with occupational exposure to the solvent 1-
bromopropane—New Jersey and Pennsylvania, 2007-2008. MMWR Morb Mortal Wkly
Rep 57: 1300-1302.
(2016). Criteria for a recommended standard: Occupational exposure to 1-bromopropane.
(CDC-2016-0003). Cincinnati, OH: National Institute for Occupational Safety and Health.
https://www.cdc.gov/niosh/docket/review/docket057a/pdfs/ctd-l-bpcriteriadocument final-
012616.pdf
(2019). Fourth National Report on Human Exposure to Environmental Chemicals, Updated
Tables, January 2019, Volume 2. Atlanta, GA: U.S. Department of Health and Human
Services, https://www.cdc.gov/exposurereport/
Chang. JCS: Krebs. KA. (1992). Evaluation of para-dichlorobenzene emissions from solid moth
repellant as a source of indoor air pollution. J Air Waste Manag Assoc 42: 1214-1217.
http://dx.doi.org/10.1080/10473289.1992.10467Q71
Chapman. PM; A.. F; P.. B. (1998). A critical evaluation of safety (uncertainty) factors for
ecological risk assessment. Environ Toxicol Chem 17: 99-108.
Cheever. KL; Marlow. KL; B'Hymer. C: Hanlev. KW: Lynch. DW. (2009). Development of an
HPLC-MS procedure for the quantification of N-acetyl-S-(n-propyl)-l-cysteine, the major
urinary metabolite of 1-bromopropane in human urine. J Chromatogr B Analyt Technol
Biomed Life Sci 877: 827-832. http://dx.doi.Org/10.1016/i.ichromb.2009.02.010
ClinTrials. (1997a). A 13-week inhalation toxicity study of a vapor formulation of ALBTA1 in the
Albino Rat. (Report No. 91190). Canada.
Page 355 of 486
CDC.
CDC.
CDC.
CDC.
-------
ClinTrials. (1997b). A 28-day inhalation toxicity study of a vapor formulation of ALBTA1 in
albino rat. (Document No. 91198). Senneville, Quebec: Sponsored by Albemarle
Corporation, Baton Rouge, LA.
CRC Industries Inc. (2017). Docket ID # EPA-HQ-OPPT-2016-0741 [EPA Report], (EPA-HQ-
OPPT-2016-0741-0018.).
Da Silva. APP; El-Bacha. T; Kyaw. N; Santos. RSd; Pa-Silva. WS; Almeida. FCL; Poian. ATP;
Galina. A. (2009). Inhibition of energy-producing pathways of HepG2 cells. Biochem J
417. http://dx.doi.org/10.1042/BJ200808Q5
De Serres. FJ: Shelby. MP. (1979). RECOMMENDATIONS ON DATA PRODUCTION AND
ANALYSIS USING THE SALMONELLA/MICROSOME MUTAGENICITY ASSAY
(pp. 159-165). (EMICBACK/31606). Pe Serres, FJ; Shelby, MP.
POW. (2018). THERMAXTM Brand Insulation, https://www.dow.com/en-
us/products/thermaxbrandinsulation#sort=%40gtitle%20ascending
Purkee. J. (2014). Cleaning with solvents: Methods and machinery. In Cleaning with solvents:
Methods and machinery. Oxford, UK: Elsevier Inc.
https://www.sciencedirect.com/book/9780323225205/cleaning-with-solvents-methods-and-
machinery
ECHA. (2012). Substance Name: 1-bromopropane [n-propyl bromide], CAS No: 106-94-5.
Member State Committee Support Pocument for Identification of 1-bromopropane [n-
propyl bromide] as a Substance of Very High Concern because of its CMR Properties.
Helsinki, Finland: European Chemical Agency.
http://echa.europa.eu/documents/10162/54958f68-9718-473a-9d64-998c6e8bld5c
ECHA. (2017). Registration dossier: 1-Bromopropane. Available online at
https://echa.europa.eu/de/registration-dossier/-/registered-dossier/15004 (accessed August
29, 2017).
Eisenberg. J: Ramsey. J. (2010). Evaluation of 1-Bromopropane Use in Four New Jersey
Commercial Pry Cleaning Facilities. In New Jersey Pepartment of Health and Senior
Services, July 2010 (pp. pp.). (NTIS/12290078). National Board of Labour Protection
(Finland), http://www.cdc.gov/niosh/hhe/reports/pdfs/2008-0175-3111.pdf
Elf Atochem. SA. (1993a). Acute oral toxicity in rats, n-propyl bromide. Study No. 10611 Tar.
Study director, Jack Clouzeau. Study performed by Centre International de Toxicologie,
Miserey, France. November 3, 1993.
Elf Atochem. SA. (1993b). Ames test—Reverse Mutation Assay on Salmonella typhimurium. n-
Propyl Bromide. HIS1005/1005A. Study performed by Sanofi Recherche. Service de
Toxicologie.
Elf Atochem. SA. (1995). Micronucleus test by intraperitoneal route in mice, n-propyl bromide.
Study No. 12122 MAS. Miserey, France: Elf Atochem Societe Anonyme, Centre
International de Toxicologie.
Elf Atochem. SA. (1996a). In vitro mammalian cell gene mutation test in L5178y TK+/- mouse
lymphoma cell of n-propyl bromide. Study no. 13293. Miserey, France.
http://vosemite.epa.gov/oppts/epatscat8.nsf/bv+Service/B9769616121757CC85256F94005
86E90/$File/8897000023 5 .pdf
Page 356 of 486
-------
Elf Atochem. SA. (1996b). In vitro mammalian cell gene mutation test in L5178Y TK+/- mouse
lymphoma cells of n-propyl bromide. (88970000235).
Elf Atochem. SA. (1997). Study of acute toxicity of n-propyl bromide administered to rats by
vapour inhalation. Determination of the 50% lethal concentration (LC50/4 hours). INERIS-
L.E.T.E. Study No. 95122. Study performed by Laboratoire d'Etudes de Toxicologie
Experimentale.
Emmerich. SJ; Gorfain. JE; Howard-Reed. C. (2003). Air and pollutant transport from attached
garages to residential living spaces - literature review and field tests. Int J Vent 2: 265-276.
Emoto. C; Murase. S; Sawada. Y; Jones. BC; Iwasaki. K. (2003). In vitro inhibitory effect of 1-
aminobenzotriazole on drug oxidations catalyzed by human cytochrome P450 enzymes: A
comparison with SKF-525A and ketoconazole. Drug Metab Pharmacokinet 18: 287-295.
http://dx.doi.org/10.2133/dmpk.18.287
Enviro Tech International. (2013). Drysolv spray testing & spotter. Material safety data sheet [Fact
Sheet], Melrose Park, IL.
http://nebula.wsimg.com/b5b721780e4046dae73c7753945cd994?AccessKevId=F58D237F
0A46DAC5AF87&disposition=0
Enviro Tech International. (2017). RE: 1-Bromopropane, Docket ID number EPA-HQ-OPPT
2016-0741. The Use of 1-bromopropane (nPB) in the Dry Cleaning Industry. (EPA-HQ-
OPPT 2016-0741-0016).
Enviro Tech International. (2019). Personal communication between R. Morford (Enviro Tech
International, Inc.) and D. Parsons (U.S. EPA) [Personal Communication],
Enviro Tech International. (2020). Comment submitted by Richard G. Morford, General Counsel
on behalf of Enviro Tech International Inc. RE: Formulation Facility Exposure Testing
Report November 2019, Docket EPA-HQ-OPPT-2016-0741 [Personal Communication],
https://www.regulations.gov/document?D=EPA-HQ-OPPT-2016-0741-0098
EPA. US. (1987). Household solvent products: A national usage survey. (EPA-OTS 560/5-87-
005). Washington, DC: Office of Toxic Substances, Office of Pesticides and Toxic
Substances.
http s: // ntrl. nti s. gov/NTRL/dashb oard/ searchResul ts. xhtml ? searchQuery=PB 88132881
EPA. US. (2019a). Draft Risk Evaluation for 1-Bromopropane - 1-BP Supplemental File:
Information on Consumer Exposure Assessment Model Input Parameters.
EPA. US. (2019b). Draft Risk Evaluation for 1-Bromopropane - 1-BP Supplemental File:
Information on Consumer Exposure Assessment Model Outputs.
EPA. US. (2019c). Draft Risk Evaluation for 1-Bromopropane (1-BP), Supplemental File:
Consumer Exposure Risk Calculations.
EPA. US. (2019d). Draft Risk Evaluation for 1-Bromopropane (1-BP), Supplemental File: Human
Health Benchmark Dose Modeling.
EPA. US. (2019e). Draft Risk Evaluation for 1-Bromopropane (1-BP), Supplemental File:
Information on Consumer Exposure Assessment Public.
EPA. US. (2019f). Draft Risk Evaluation for 1-Bromopropane (1-BP), Supplemental File:
Information on Occupational Exposure Assessment. (Docket EPA-HQ-OPPT-2019-0236).
EPA. US. (2019g). Draft Risk Evaluation for 1-Bromopropane (1-BP), Supplemental File:
Occupational Risk Calculator.
Page 357 of 486
-------
EPA. US. (2019h). Draft Risk Evaluation for 1-Bromopropane (1-BP), Systematic Review
Supplemental File: Data Extraction for Consumer Exposure.
EPA. US. (2019i). Draft Risk Evaluation for 1-Bromopropane (1-BP), Systematic Review
Supplemental File: Data Extraction Tables for Environmental Fate and Transport Studies.
EPA. US. (2019j). Draft Risk Evaluation for 1-Bromopropane (1-BP), Systematic Review
Supplemental File: Data Quality Evaluation for Consumer Exposure.
EPA. US. (2019k). Draft Risk Evaluation for 1-Bromopropane (1-BP), Systematic Review
Supplemental File: Data Quality Evaluation of Ecological Hazard Studies.
EPA. US. (20191). Draft Risk Evaluation for 1-Bromopropane (1-BP), Systematic Review
Supplemental File: Data Quality Evaluation of Environmental Fate and Transport Studies.
EPA. US. (2019m). Draft Risk Evaluation for 1-Bromopropane (1-BP), Systematic Review
Supplemental File: Data Quality Evaluation of Environmental Release and Occupational
Exposure Data.
EPA. US. (2019n). Draft Risk Evaluation for 1-Bromopropane (1-BP), Systematic Review
Supplemental File: Data Quality Evaluation of Environmental Release and Occupational
Exposure Data for Common Sources.
EPA. US. (2019o). Draft Risk Evaluation for 1-Bromopropane (1-BP), Systematic Review
Supplemental File: Data Quality Evaluation of Human Health Hazard Studies.
EPA. US. (2019p). Draft Risk Evaluation for 1-Bromopropane (1-BP), Systematic Review
Supplemental File: Data Quality Evaluation of Human Health Hazard Studies -
Epidemiologic Studies.
EPA. US. (2019q). Draft Risk Evaluation for 1-Bromopropane (1-BP), Systematic Review
Supplemental File: Updates to the Data Quality Criteria for Epidemiological Studies.
ERG. (2001). Draft generic scenario. Use of vapor degreasers. Chantilly, VA: Eastern Research
Group.
ERG. (2005). [Letter from Eric Goehl and Jennifer O'Neil, Eastern Research group, Inc, to Dry
Cleaning Docket, Subject: Background information document]. Available online at
http://www3.epa.gov/airtoxics/drvperc/ll-14-05background.pdf
Federal Register. (1999). 64 FR 60194: Category for Persistent, Bioaccumulative, and Toxic New
Chemical Substances (pp. 60194-60204). Register, F.
Fonda. M. (1976). Bromopyruvate Inactivation of Glutamate Apodecarboxylase. J Biol Chem 251:
229-235.
Frasch. HF; Bunge. AL. (2015). The transient dermal exposure II: post-exposure absorption and
evaporation of volatile compounds. J Pharm Sci 104: 1499-1507.
http://dx.doi.org/10.1002/ips.24334
Frasch. HF: Dotson. GS: Barbero. AM. (2011). In vitro human epidermal penetration of 1-
bromopropane. J Toxicol Environ Health A 74: 1249-1260.
http://dx.doi.org/10.1080/15287394.2011.595666
Fueta. Y; Fukuda. T; Ishidao. T; Hori. H. (2004). Electrophysiology and immunohistochemistry in
the hippocampal cal and the dentate gyrus of rats chronically exposed to 1-bromopropane,
a substitute for specific chlorofluorocarbons. Neuroscience 124: 593-603.
http://dx.doi.Org/10.1016/i.neuroscience.2003.12.025
Page 358 of 486
-------
Fueta. Y; Fukunaga. K; Ishidao. T; Hori. H. (2002a). Hyperexcitability and changes in activities of
Ca2+/calmodulin-dependent kinase II and mitogen-activated protein kinase in the
hippocampus of rats exposed to 1-bromopropane. Life Sci 72: 521-529.
http://dx.doi.org/10.1016/S0024-3205('02X)2247-6
Fueta. Y; Ishidao. T; Arashidani. K; Endo. Y; Hori. H. (2002b). Hyperexcitability of the
hippocampal CA1 and the dentate gyrus in rats subchronically exposed to a substitute for
chlorofluorocarbons, 1-bromopropane vapor. J Occup Health 44: 156-165.
http://dx.doi.org/10.1539/ioh.44.156
Fueta. Y; Ishidao. T; Kasai. T; Hori. H; Arashidani. K. (2000). Decreased paired-pulse inhibition
in the dentate gyrus of the brain in rats exposed to 1-bromopropane vapor [Letter], J Occup
Health 42: 149-151. http://dx.doi.org/10.1539/ioh.42.149
Fueta. Y; Ishidao. T; Ueno. S: Yoshida. Y; Kunugita. N: Hori. H. (2007). New approach to risk
assessment of central neurotoxicity induced by 1-bromopropane using animal models.
Neurotoxicology 28: 270-273. http://dx.doi.Org/10.1016/i.neuro.2006.05.003
Fueta. Y; Ueno. S: Ishidao. T; Kanemitsu. M; Hori. H. (2013). Prenatal exposure to 1-
Bromopropane changes basic excitability of hippocampus and inhibits the behaviors iduced
by kainic acid and pentylenetetrazole in the rat offspring during lactation period.
Toxicologist 132: Abstract No. 1389.
Furuhashi. K; Kitoh. J: Tsukamura. H; Maeda. K; Wang. H; Li. W: Ichihara. S: Nakaiima. T;
Ichihara. G. (2006). Effects of exposure of rat dams to 1-bromopropane during pregnancy
and lactation on growth and sexual maturation of their offspring. Toxicology 224: 219-228.
http://dx.doi.Org/10.1016/i.tox.2006.04.044
Ganapathy-Kanniappan. S: Geschwind. JFH; Kunjithapatham. R; Buiis. M; Yossen. J:
Tchernyshyov. I; Cole. RH; Sved. LH; Rao. PP; Ota. S: Vali. M. (2009). Glyceraldehyde-3-
phosphate Dehydrogenase (GAPDH). Anticancer Res 29: 4909-4918.
Garner. CE; Liang. S: Yin. L; Yu. X. (2015). Physiologically based pharmacokinetic modeling for
1-bromopropane in F344 rats using gas uptake inhalation experiments. Toxicol Sci 145: 23-
36. http://dx.doi.org/10.1093/toxsci/kfv018
Garner. CE: Sloan. C: Sumner. SC: Burgess. J: Davis. J: Etheridge. A: Parham. A: Ghanavem. BI.
(2007). CYP2E1-catalyzed oxidation contributes to the sperm toxicity of 1-bromopropane
in mice. Biol Reprod 76: 496-505. http://dx.doi.org/10.1095/biolreprod.106.055004
Garner. CE: Sumner. SC: Davis. JG: Burgess. JP; Yueh. Y; Demeter. J: Zhan. O: Valentine. J:
Jeffcoat. AR; Burka. LT; Mathews. JM. (2006). Metabolism and disposition of 1-
bromopropane in rats and mice following inhalation or intravenous administration. Toxicol
Appl Pharmacol 215: 23-36. http://dx.doi.Org/10.1016/i.taap.2006.01.010
Garner. CE: Yu. X. (2014). Species and sex-dependent toxicokinetics of 1-bromopropane: the role
of hepatic cytochrome P450 oxidation and glutathione (GSH). Xenobiotica 44: 644-656.
http://dx.doi.org/10.3109/00498254.2Q13.879624
Geiger. PL: Call. DJ: Brooke. LT. (1988). Acute toxicities of organic chemicals to fathead
minnows (Pimephales promelas): Volume IV. Superior, WI: University of Wisconsin-
Superior, Center for Lake Superior Environmental Studies.
Giesv. JP: Granev. RL. (1989). Recent Developments in and Intercomparisons of Acute and
Chronic Bioassays and Bioindicators. 188/189: 21-60.
Page 359 of 486
-------
Guo. Y; Yuan. H; Jiang. L; Yang. J; Zeng. T; Xie. K; Zhang. C; Zhao. X. (2015). Involvement of
decreased neuroglobin protein level in cognitive dysfunction induced by 1-bromopropane
in rats. Brain Res 1600: 1-16. http://dx.doi.Org/10.1016/i.brainres.2014.12.046
Guo. Z. (2002). Review of indoor emission source models Part 1 Overview [Review], Environ
Pollut 120: 533-549.
Hanlev. KW: Petersen. M; Curwin. BP: Sanderson. WT. (2006a). Urinary bromide and breathing
zone concentrations of 1-bromopropane from workers exposed to flexible foam spray
adhesives.
Hanlev. KW: Petersen. M; Curwin. BP: Sanderson. WT. (2006b). Urinary bromide and breathing
zone concentrations of 1-bromopropane from workers exposed to flexible foam spray
adhesives. Ann Occup Hyg 50: 599-607. http://dx.doi.org/10.1093/annhyg/mel020
Hanlev. KW: Petersen. MR: Cheever. KL; Luo. L. (2009). N-acetyl-S-(n-propyl)-l-cysteine in
urine from workers exposed to 1-bromopropane in foam cushion spray adhesives. Ann
Occup Hyg 53: 759-769. http://dx.doi.org/10.1093/annhyg/mep051
Hanlev. KW: Petersen. MR: Cheever. KL: Luo. L. (2010). Bromide and N-acetyl-S-(n-propyl)-L-
cysteine in urine from workers exposed to 1-bromopropane solvents from vapor degreasing
or adhesive manufacturing. Int Arch Occup Environ Health 83: 571-584.
http://dx.doi. org/10.1007/s00420-010-0524-4
Hansch. C. (1995). Fundamentals and applications in chemistry and biology - hydrophobic,
electronic and steric constants. In Exploring QSAR. Washington PC: American Chemical
Society Professional Reference Book/Oxford University Press.
Hasspieler. B: Haffner. P: Stellies. M: Adeli. K. (2006). Toxicological assessment of industrial
solvents using human cell bioassays: assessment of short-term cytotoxicity and long-term
genotoxicity potential. Toxicol Ind Health 22: 301-315.
http://dx.doi.org/10.1177/074823370607Q312
Havnes. WM: Lide. PR. (2010). Editor
CRC handbook of chemistry and physics: A ready-reference book of chemical and physical data
(91st ed.). Boca Raton, FL: CRC Press.
Honma. T; Suda. M: Miyagawa. M. (2003). Inhalation of 1-bromopropane causes excitation in the
central nervous system of male F344 rats. Neurotoxicology 24: 563-575.
http://dx.doi. org/10.1016/SO161 -813X(03V)0049-4
HSPB. (2017). Hazardous substances data bank: 1-Bromopropane [Patabase], Rockville, MP:
U.S. National Library of Medicine. Retrieved from
https://toxnet.nlm. nih.gov/newtoxnet/hsdb. htm
HSIA. (2010). Petition to add n-propyl bromide to list of hazardous air pollutants regulate under
section 112 of the Clean Air Act [with cover letter date 10/28/2010], Arlington, VA.
http://www.hsia.org/news/nPBPetitionsigned.pdf
Huang. Z: Ichihara. S: Oikawa. S: Chang. J: Zhang. L: Hu. S: Huang. H: Ichihara. G. (2015).
Hippocampal phosphoproteomics ofF344 rats exposed to 1-Bromopropane. Toxicol Appl
Pharmacol 282: 151-160. http://dx.doi.Org/10.1016/i.taap.2014.10.016
Huang. Z: Ichihara. S: Oikawa. S: Chang. J: Zhang. L: Subramanian. K: Mohideen. SS: Ichihara.
G. (2012). Proteomic identification of carbonylated proteins in F344 rat hippocampus after
Page 360 of 486
-------
1-bromopropane exposure. Toxicol Appl Pharmacol 263: 44-52.
http://dx.doi.Org/10.1016/i.taap.2012.05.021
Huang. Z; Ichihara. S: Oikawa. S: Chang. J: Zhang. L; Takahashi. M: Subramanian. K: Mohideen.
SS: Wang. Y; Ichihara. G. (2011). Proteomic analysis of hippocampal proteins of F344 rats
exposed to 1-bromopropane. Toxicol Appl Pharmacol 257: 93-101.
http://dx.doi.Org/10.1016/i.taap.2011.08.023
Hughes. TJ: Simmons. DM: Monteith. LG: Claxton. LP. (1987). Vaporization technique to
measure mutagenic activity of volatile organic chemicals in the Ames/Salmonella assay.
Environ Mutagen 9: 421-441. http://dx.doi.org/10.1002/em.28600904Q8
Huntingdon Life Sciences. (1999). A range-finding development/reproductive toxicity study of 1-
Bromopropane in rats via whole body inhalation exposure. Final report. (Study No. 98-
4140. 8EHQ-0799-14346).
http://vosemite. epa.gov/oppts/epatscat8. nsf/bv+Service/D275E580BB932A308525695A00
48B A00/$File/89990000271 .pdf
Huntingdon Life Sciences. (2001). A developmental toxicity study in rat via whole body inhalation
exposure (with cover letter dated 9/18/2001). (Study No. 98-4141; docket number A-2001-
07). East Millstone, NJ: Study sponsored by Brominated Solvents Committee (BSOC).
I ARC. (1994). IARC Monographs on the Evaluation of Carcinogenic Risks to Humans. Propylene
oxide, vol. 60, pp. 181-213. Lyon, France.
http://monographs.iarc.fr/ENG/Monographs/vol60/mono60-9.pdf
IARC. (1999a). l,2-dibromo-3-chloropropane [IARC Monograph], In IARC Working Group on
the Evaluation of Carcinogenic Risks to Humans (pp. 479-500). Lyon, France: World
Health Organization. http://monographs.iarc.fr/ENG/Monographs/vol71/mono71-20.pdf
IARC. (1999b). 1,2-dichloroethane [IARC Monograph], In IARC Working Group on the
Evaluation of Carcinogenic Risks to Humans (pp. 501-529). Lyon, France: World Health
Organization, http://monographs.iarc.fr/ENG/Monographs/vol7l/mono71-21 .pdf
IARC. (1999c). l,2,3-tris(chloromethoxy)propane [IARC Monograph], In IARC Working Group
on the Evaluation of Carcinogenic Risks to Humans (pp. 1549-1550). Lyon, France: World
Health Organization. http://monographs.iarc.fr/ENG/Monographs/vol71/mono71-115.pdf
IARC. (1999d). Dichloromethane [IARC Monograph], In IARC Monographs on the Evaluation of
the Carcinogenic Risk of Chemicals to Humans (pp. 251-315). Lyon, France: World Health
Organization, http://monographs.iarc.fr/ENG/Monographs/vol7l/mono71 -10.pdf
IARC. (1999e). Ethylene dibromide (1,2-dibromoethane) [IARC Monograph], In IARC Working
Group on the Evaluation of Carcinogenic Risks to Humans (pp. 641-669). Lyon, France:
World Health Organization. http://monographs.iarc.fr/ENG/Monographs/vol71/mono71-
28.pdf
IARC. (2000). Glycidol in some industrial chemicals in IARC monographs on the evaluation of
carcinogenic risks to humans (pp. 469-489). Lyon, France.
http://monographs.iarc.fr/ENG/Monographs/vol77/mono77-19.pdf
IARC. (2018). IARC Monographs on the Evaluation of Carcinogenic Risks to Humans
Some Industrial Chemicals. Lyon, France: World Health Organization.
https://monographs.iarc.fr/wp-content/uploads/2018/06/monol 15 .pdf
Page 361 of 486
-------
Ichihara. G; Kitoh. J; Yu. X; Asaeda. N; Iwai. H; Kumazawa. T; Shibata. E; Yamada. T; Wang. H;
Xie. Z; Takeuchi. Y. (2000a). 1-Bromopropane, an alternative to ozone layer depleting
solvents, is dose-dependently neurotoxic to rats in long-term inhalation exposure. Toxicol
Sci 55: 116-123. http://dx.doi.Org/10.1093/toxsci/55.l.l 16
Ichihara. G: Li. W: Ding. X: Peng. S: Yu. X: Shibata. E; Yamada. T; Wang. H; Itohara. S: Kanno.
S: Sakai. K; Ito. H; Kanefusa. K; Takeuchi. Y. (2004a). A survey on exposure level, health
status, and biomarkers in workers exposed to 1-bromopropane. Am J Ind Med 45: 63-75.
http://dx.doi.org/10.1002/aiim.1032Q
Ichihara. G: Li. W: Shibata. E; Ding. X: Wang. H; Liang. Y; Peng. S: Itohara. S: Kamijima. M;
Fan. Q: Zhang. Y; Zhong. E; Wu. X: Valentine. WM; Takeuchi. Y. (2004b). Neurologic
abnormalities in workers of a 1-bromopropane factory. Environ Health Perspect 112: 1319-
1325. http://dx.doi.org/10.1289/ehp.6995
Ichihara. G: Miller. JK; Ziolkokwska. A: Itohara. S: Takeuchi. Y. (2002). Neurological disorders in
three workers exposed to 1-bromopropane. J Occup Health 44: 1-7.
http://dx.doi.Org/10.1539/ioh.44.l
Ichihara. G: Wang. H; Zhang. L; Wakai. K; Li. W: Ding. X: Shibata. E; Zhou. Z; Wang. O; Li. J:
Ichihara. S: Takeuchi. Y. (2011). Dose-dependent neurologic abnormalities in workers
exposed to 1-bromopropane: authors' response [Letter], J Occup Environ Med 53: 1095-
1098. http://dx.doi.org/10.1097/JQM.ObO 13e3182300a4f
Ichihara. G: Yu. X: Kitoh. J: Asaeda. N: Kumazawa. T; Iwai. H; Shibata. E; Yamada. T; Wang. H;
Xie. Z; Maeda. K; Tsukamura. H; Takeuchi. Y. (2000b). Reproductive toxicity of 1-
bromopropane, a newly introduced alternative to ozone layer depleting solvents, in male
rats. Toxicol Sci 54: 416-423. http://dx.doi.Org/10.1093/toxsci/54.2.416
ICRP. (1975). Report of the task group on reference man. In ICRP Publication 23. Oxford, UK:
Pergamon Press.
http://ani.sagepub.com/site/includefiles/icrp publications collection.xhtml
IRTA. (2016). Alternative Compliance Strategies for Enclosed and Conveyorized Vapor
Degreasers under a Prohibition of Trichloroethylene. Draft.
Ishidao. T; Kunugita. N: Fueta. Y; Arashidani. K; Hori. H. (2002). Effects of inhaled 1-
bromopropane vapor on rat metabolism. Toxicol Lett 134: 237-243.
http://dx.doi. org/10.1016/S03 78-4274(02V)0171-6
Jain. RB. (2015). Distributions of selected urinary metabolites of volatile organic compounds by
age, gender, race/ethnicity, and smoking status in a representative sample of U.S. adults.
Environ Toxicol Pharmacol 40: 471-479. http://dx.doi.Org/10.1016/i.etap.2015.07.018
Janssen. DB; Jager. D; Witholt. B. (1987). Degradation of n-haloalkanes and alpha, omega-
dihaloalkanes by wild-type and mutants of Acinetobacter sp. strain GJ70. Appl Environ
Microbiol 53: 561-566.
Javiock. MA. (1994). Back pressure modeling of indoor air concentrations from volatilizing
sources. Am Ind Hyg Assoc J 55: 230-235. http://dx.doi.org/10.1080/15428119491019078
Jones. AR; Walsh. DA. (1979). The oxidative metabolism of 1-bromopropane in the rat.
Xenobiotica 9: 763-772. http://dx.doi.org/10.3109/00498257909Q42344
Page 362 of 486
-------
Kane. Ta. (2015). The Great Port Mismatch. U.S. Goods Trade and International Transportation.
Tomer and Kane, https://www.brookings.edu/wp-
content/uploads/2015/06/brgkssrvygcifrei ghtnetworks.pdf
Kanegsberg. B; Kanegsberg. E. (2011). Handbook of critical cleaning, applications, processes, and
controls. In Handbook for critical cleaning, cleaning agents and systems. Boca Raton: CRC
Press. http://dx.doi.org/10.1201/blQ858
Kaneko. T; Kim. HY; Wang. PY; Sato. A. (1997). Partition coefficients and hepatic metabolism in
vitro of 1- and 2-bromopropanes. J Occup Health 39: 341-342.
http://dx.doi.org/10.1539/ioh.39.341
Kawai. T; Takeuchi. A: Miyama. Y; Sakamto. K; Zhang. ZW: Higashikawa. K; Ikeda. M. (2001).
Biological monitoring of occupational exposure to 1-bromopropane by means of urinalysis
for 1-bromopropane and bromide ion. Biomarkers 6: 303-312.
http://dx.doi.org/10.1080/13547500110Q34817
Kenaga. EE. (1982). Predictability of chronic toxicity from acute toxicity of chemicals in fish and
aquatic invertebrates. Environ Toxicol Chem 1: 347-358.
http://dx.doi.org/10.1002/etc.562001041Q
Khan. S: O'Brien. PJ. (1991). 1-Bromoalkanes as new potent nontoxic glutathione depletors in
isolated rat hepatocytes. Biochem Biophys Res Commun 179: 436-441.
http://dx.doi.org/10.1016/0006-291X(9n91389-T
Kienzler. A: Haider. M; A.. W. (2017). Waiving chronic fish tests: possible use of acute-to-chronic
relationships and interspecies correlations. Toxicol Environ Chem 99: 1129-1151.
Kim. H; Chung. J: Chung. Y; Kim. K; Maeng. S: Hang. C: Lim. C: Lee. J: Kim. K; Lee. K; et al.
(1998). Toxicological studies on inhalation of 1-bromopropane using rats. Report submitted
to the Industrial Health Research Institute. Yongsan Gu, Republic of Korea: Korea
Industrial Safety Corporation.
Kim. HY: Chung. YH; Jeong. JH; Lee. YM; Sur. GS: Kang. JK. (1999a). Acute and repeated
inhalation toxicity of 1-bromopropane in SD rats. J Occup Health 41: 121-128.
http://dx.doi.org/10.1539/Joh.41.121
Kim. JS: Ahn. KJ: Kim. JA: Kim. HM: Lee. JD: Lee. JM: Kim. SJ: Park. JH. (2008). Role of
reactive oxygen species-mediated mitochondrial dysregulation in 3-bromopyruvate induced
cell death in hepatoma cells : ROS-mediated cell death by 3-BrPA. J Bioenerg Biomembr
40: 607-618. http://dx.doi.org/10.1007/slQ863-008-9188-0
Kim. KW: Kim. HY: Park. SS: Jeong. HS: Park. SH: Lee. JY: Jeong. JH: Moon. YH. (1999b).
Gender differences in activity and induction of hepatic microsomal cytochrome P-450 by 1-
bromopropane in Sprague-Dawley rats. J Biochem Mol Biol 32: 232-238.
Kissel. JC: Bunge. AL: Frasch. HF; Kasting. GB. (2018). Dermal Exposure and Absorption of
Chemicals. In CA McQueen (Ed.), (3rd ed., pp. 112-127). Oxford, UK: Elsevier Ltd.
http://dx.doi.org/10.1016/B978-0-08-046884-6.001Q5-6
Ko. YH: Smith. B; Wang. Y; Pomper. M; Rini. DA: Torbenson. MS: Hullihen. J: Pedersen. PL.
(2004). Advanced cancers: eradication in all cases using 3-bromopyruvate therapy to
deplete ATP. Biochem Biophys Res Commun 324: 269-275.
http://dx.doi.Org/10.1016/i.bbrc.2004.09.047
Page 363 of 486
-------
Krause. RJ; Glocke. SC; Elfarra. AA. (2002). Sulfoxides as urinary metabolites of S-ALLYL-L-
CYSTEINE in rats: Evidence for the involvement of flavin-containing monooxygenases.
Drug Metab Dispos 30: 1137-1142. http://dx.doi.Org/10.l 124/dmd.30.10.1137
Lee. SK; Jeon. TW: Kim. YB; Lee. ES: Jeong. HG: Jeong. TC. (2007). Role of glutathione
conjugation in the hepatotoxicity and immunotoxicity induced by 1-bromopropane in
female BALB/c mice. J Appl Toxicol 27: 358-367. http://dx.doi.org/10.1002/iat.1214
Li. W: Shibata. E; Zhou. Z; Ichihara. S: Wang. H; Wang. O; Li. J: Zhang. L; Wakai. K; Takeuchi.
Y; Ding. X: Ichihara. G. (2010). Dose-dependent neurologic abnormalities in workers
exposed to 1-bromopropane. J Occup Environ Med 52: 769-777.
http://dx.doi. org /10.1097/JQM. ObO 13 e3181 eaded7
Liu. F; Ichihara. S: Mohideen. SS: Sai. U: Kitoh. J: Ichihara. G. (2009). Comparative study on
susceptibility to 1-bromopropane in three mice strains. Toxicol Sci 112: 100-110.
http://dx.doi.org/10.1093/toxsci/kfpl73
Liu. F; Ichihara. S: Valentine. WM; Itoh. K; Yamamoto. M; Sheik Mohideen. S: Kitoh. J: Ichihara.
G. (2010). Increased susceptibility of Nrf2-null mice to 1-bromopropane-induced
hepatotoxicity. Toxicol Sci 115: 596-606. http://dx.doi.org/10.1093/toxsci/kfq075
Lopachin. RM; Gavin. T; Petersen. PR: Barber. DS. (2009). Molecular mechanisms of 4-hydroxy-
2-nonenal and acrolein toxicity: Nucleophilic targets and adduct formation [Review], Chem
Res Toxicol 22: 1499-1508. http://dx.doi.org/10.1021/tx900147g
Lowe. PN: Perham. RN. (1984). Bromopyruvate as an active-site-directed inhibitor of the pyruvate
dehydrogenase multienzyme complex from Escherichia coli. Biochemistry 23: 91-97.
http://dx.doi. org/10.1021/Bi00296a015
Mabev. W: Mill. T. (1978). Critical review of hydrolysis of organic compounds in water under
environmental conditions [Review], J Phys Chem Ref Data 7: 383-415.
Macchioni. L; Davidescu. M; Sciaccaluga. M; Marchetti. C: Migliorati. G: Coaccioli. S: Roberti.
R; Corazzi. L; Castigli. E. (2011). Mitochondrial dysfunction and effect of antiglycolytic
bromopyruvic acid in GL15 glioblastoma cells. J Bioenerg Biomembr 43: 507-518.
http://dx.doi.org/10.1007/slQ863-011-9375-2
Maiersik. JJ; Caravati. EM: Steffens. JD. (2007). Severe neurotoxicity associated with exposure to
the solvent 1-bromopropane (n-propyl bromide). Clin Toxicol 45: 270-276.
http://dx.doi.org/10.1080/155636507Q1226218
Marquart. H; Franken. R; Goede. H; Fransman. W: Schinkel. J. (2017). Validation of the dermal
exposure model in ECETOC TRA. Annals of Work Exposures and Health 61: 854-871.
http ://dx. doi. org /10.1093/annweh/wxx05 9
MassDEP. (2013). Alternative dry cleaning technologies comparative analysis worksheet. Boston,
MA. http://www.mass.gov/eea/docs/dep/service/online/dc-companal.pdf
Mathias. PI: Cheever. KL; Hanlev. KW: Marlow. KL; Johnson. BC: B'Hymer. C. (2012).
Comparison and evaluation of urinary biomarkers for occupational exposure to spray
adhesives containing 1-bromopropane. Toxicol Mech Meth 22: 526-532.
http://dx.doi.org/10.3109/15376516.2012.686536
May. M; W.. D; S.. G: T.. J: S.. H. (2016). Evaluation of acute-to-chronic ratios of fish and
Daphnia to predict acceptable no-effect levels. Environ Sci Eur 28: 16.
Page 364 of 486
-------
Meulenberg. CJ; Viiverberg. HP. (2000). Empirical relations predicting human and rat tissue: Air
partition coefficients of volatile organic compounds. Toxicol Appl Pharmacol 165: 206-
216. http://dx.doi.org/10.1006/taap.200Q.8929
Miller. B. (2019). Comment submitted by Bob Miller, Jr., Senior Director, Global Product
Stewardship, Albemarle Corporation regarding 1-Bromopropane. Docket ID: EPA-HQ-
OPPT-2019-0235-0029. (Docket ID: EPA-HQ-OPPT-2019-0235-0029). Miller, B.
https://www.regulations.gov/document?D=EPA-HO-QPPT-2019-0235-0029
Mitchell. AE; Zheng. J: Hammock. BP: Lo Bello. M; Jones. AD. (1998). Structural and functional
consequences of haloenol lactone inactivation of murine and human glutathione S-
transferase. Biochemistry 37: 6752-6759. http://dx.doi.org/10.1021/bi971846r
Mohideen. SS: Ichihara. G: Ichihara. S: Nakamura. S. (2011). Exposure to 1-bromopropane causes
degeneration of noradrenergic axons in the rat brain. Toxicology 285: 67-71.
http://dx.doi.Org/10.1016/i.tox.2011.04.005
Mohideen. SS: Ichihara. S: Banu. S: Liu. F; Kitoh. J: Ichihara. G. (2009). Changes in
neurotransmitter receptor expression levels in rat brain after 4-week exposure to 1-
bromopropane. Neurotoxicology 30: 1078-1083.
http://dx.doi.Org/10.1016/i.neuro.2009.06.007
Mohideen. SS: Ichihara. S: Subramanian. K; Huang. Z; Naito. H; Kitoh. J: Ichihara. G. (2013).
Effects of exposure to 1-bromopropane on astrocytes and oligodendrocytes in rat brain. J
Occup Health 55: 29-38. http://dx.doi.org/10.1539/ioh.12-0118-0A
Morgan. PL: Nvska. A: Harbo. SJ: Grumbein. SL; Dill. JA; Rovcroft. JH; Kissling. GE; Cesta.
MF. (2011). Multisite carcinogenicity and respiratory toxicity of inhaled 1-bromopropane
in rats and mice. Toxicol Pathol 39: 938-948. http://dx.doi.Org/10.l 177/0192623311416374
NCPOL. (2013). A Health and Safety Guide for 1-bromopropane (n-propyl bromide). In
Occupational Safety and Health Pivision. Raleigh, NC: North Carolina Pepartment of
Labor, http://digital.ncdcr.gov/cdm/ref/collection/pl6062coll9/id/148494
Neafsev. P; Ginsberg. G: Hattis. P; Johns. PO: Guvton. KZ; Sonawane. B. (2009). Genetic
polymorphism in CYP2E1: Population distribution of CYP2E1 activity [Review], J Toxicol
Environ Health B Crit Rev 12: 362-388. http://dx.doi.org/10.1080/109374009Q3158359
Nepal. MR: Noh. K; Shah. S: Bist. G: Lee. ES: Jeong. TC. (2019). Identification of PNA and
glutathione adducts in male Sprague-Pawley rats exposed to 1-Bromopropane. J Toxicol
Environ Health A 82: 502-513.
NEWMOA. (2001). Pollution prevention technology profile - Closed loop vapor degreasing.
Boston, MA. http://www.newmoa.org/prevention/p2tech/ProfileVaporPegreasing.pdf
NFPA. (2010). Fire protection guide to hazardous materials (14th ed.). Quincy, MA.
NIOSH. (1997). Control of health and safety hazards in commercial drycleaners: chemical
exposures, fire hazards, and ergonomic risk factors. In Education and Information Pivision.
(PHHS (NIOSH) Publication Number 97-150). Atlanta, GA.
http://www.cdc.gov/niosh/docs/97-150/
NIOSH. (2002a). Health Hazard Evaluation Report No. 98-0153-2883. Custom Products Inc.
Mooreville. NC. (98-0153-2883). National Instutute for Occupational Safety and Health.
http://www.cdc.gov/niosh/hhe/reports/pdfs/1998-0153-2883.pdf
Page 365 of 486
-------
NIOSH. (2002b). Health hazard evaluation report: HETA 2000-0410-2891, STN Cushion
Company, Thomasville, North Carolina. (HETA 2000-410-2891.). Cincinnati, OH.
http://www.cdc. gov/niosh/hhe/reports/pdfs/2000-0410-2891 .pdf
NIOSH. (2002c). Health Hazard Evaluation Report: HETA # 2000-0410-2891 STN Cushion
Company, Thomasville, North Carolina. (HETA 2000-410-2891.). Cincinnati, OH.
http://www.cdc. gov/niosh/hhe/reports/pdfs/2000-0410-2891 .pdf
NIOSH. (2003a). Hazard Evaluation Report: HETA 99-260-2906. Marx Industries Inc., Sawmills,
NC. (HETA 99-260-2906). NIOSH Publication Office, Cincinnati, OH: National Institute
for Occupational Health and Safety, http://www.cdc.gov/niosh/hhe/reports/pdfs/1999-0260-
2906.pdf
NIOSH. (2003b). NIOSH Health Hazard Evaluation Report: HETA No. 99-0260-2906, Marx
Industries, Inc., Sawmills, North Carolina. In Hazard Evaluation and Technical Assisstance
Branch. (HETA 99-260-2906). Cincinnati, OH: National Institute for Occupational Health
and Safety, http://www.cdc.gov/niosh/hhe/reports/pdfs/1999-0260-2906.pdf
NIOSH. (2007). Workers' exposures to n-propyl bromide at an adhesives and coating
manufacturer. Cincinnati, OH: NIOSH Division of Surveillance, Hazard Evaluation and
Field Studies, http://www.cdc.gov/niosh/nioshtic-2/20031869.html
NIOSH. (2010). Evaluation of 1-bromopropane use in four New jersey Commercial Dry Cleaning
Facilities. (HETA 2008-0175-3111). http://www.cdc.gov/niosh/hhe/reports/pdfs/2008-
0175-3111.pdf
NRC. (2001). Standing Operating Procedures for Developing Acute Exposure Guideline Levels for
Hazardous Chemicals, http://www.nap.edu/catalog.php7record id=10122
NTP. (1989a). NTP Toxicology and Carcinogenesis Studies of Tribromomethane (Bromoform)
(CAS No. 75-25-2) in F344/N Rats and B6C3F1 Mice (Gavage Studies). 350: 1-194.
NTP. (1989b). Toxicology and carcinogenesis studies of bromoethane in F344/N rats and B6C3F1
mice (inhalation studies). (Report No. 363). RTP, NC: National Toxicology Program
Technical Report Series, http://ntp.niehs.nih.gov/ntp/htdocs/lt rptsZtr363.pdf
NTP. (1990). Toxicology and carcinogenesis studies of glycidol (CAS no. 556-52-5) in F344/N
rats and B6C3Fi mice (gavage studies) [NTP], (NIH Pub No. 90-2829; NTP TR 374).
Research Triangle Park, NC: National Institute of Environmental Health Sciences.
https://ntp.niehs.nih.gov/ntp/htdocs/lt rptsZtr374.pdf
NTP. (201 la). NTP technical report on the toxicology and carcinogenesis studies of 1-
bromopropane (CAS No. 106-94-5) in F344/N rats and B6C3F1 mice (inhalation studies).
(NTP TR 564; NIH Publication No. 11-5906). Research Triangle Park, NC.
http://ntp.niehs.nih.gov/ntp/htdocs/lt rptsZtr564.pdf
NTP. (201 lb). Toxicology and carcinogenesis studies of 1-bromopropane (CAS No. 106-94-5) in
F344/N rats andB6C3Fl mice (inhalation studies) [NTP] (pp. 1-190). (ISSN 0888-8051
NTP TR 564; NIH Publication No. 11-5906). Research Triangle Park, NC.
http://ntp.niehs.nih.gov/ntp/htdocs/LT rptsZTR564.pdf
NTP. (2013a). Draft report on carcinogens, monograph for 1-bromopropane. Research Triangle
Park, NC.
Page 366 of 486
-------
http://ntp.niehs.nih.gov/ntp/about ntp/monopeerrvw/2013/march/draftroclbpmonograph 5
08.pdf
NTP. (2013b). Report on carcinogens. Monograph for 1-bromopropane (Final) (pp. 1-168). (NIH
Publication No. 13-5982). Research Triangle Park, NC.
http://ntp.niehs.nih.gov/ntp/roc/thirteenth/monographs final/lbromopropane 508.pdf
NTP. (2014). Report on Carcinogenes. 13th Edition.
http://ntp.niehs.nih.gov/pubhealth/roc/rocl3/index.html
O'Neil. MJ. (2013). The Merck index: An encyclopedia of chemicals, drugs, and biologicals. In MJ
O'Neil (Ed.), (15th ed.). Cambridge, UK: Royal Society of Chemistry.
OECD. (1997). OECD guidelines for the testing of chemicals
Section 4: Test No. 471: Bacterial Reverse Mutation Test. Paris, France.
OECD. (2013). OECD guidelines for the testing of chemicals
Section 4: Test no. 488: Transgenic Rodent Somatic and Germ Cell Gene Mutation Assays. Paris,
France.
Ohnishi. A: Ishidao. T; Kasai. T; Arashidani. K; Hori. H. (1999). [Neurotoxicity of 1-
bromopropane in rats], J UOEH 21: 23-28.
OSHA. (2005). Reducing worker exposure to perchloroethylene (PERC) in dry cleaning. (OSHA
3253-05N). Washington, DC: U.S. Department of Labor, Occupational Safety & Health
Administration, https://www.osha.gov/dsg/guidance/perc.html
OSHA. (2013a). 1-Bromopropane Manufacturing Site Visit Report - Company A. Draft - Final.
Prepared by Project Enhancement Corporation.
OSHA. (2013b). 1-Bromopropane, Inspection/Case File Summary.
OSHA. (2013c). OSHA/NIOSH Hazard Alert: 1-Bromopropane. 7.
OSFLA (2013d). OSHA/NIOSH hazard alert: 1-Bromopropane. (OSHA - HA-3676-2013).
Washington, DC: Occupational Safety & Health Administration, National Institute for
Occupational Safety and Health.
https://www.osha.gov/dts/hazardalerts/lbromopropane hazard alert.html
OSHA: NIOSH. (2013). Hazard alert: 1-Bromopropane. Washington, DC: Occupational Safety and
Health Administration & National Institute for Occupational Safety and Health.
http://www.cdc.gov/niosh/nioshtic-2/20031537.html
Patty. FA: Fas sett. DW: Irish. DP. (1963). Industrial hygiene and toxicology: Vol. II: Toxicology.
In FA Patty; DW Fassett; DD Irish (Eds.), Industrial hygiene and toxicology: Vol II:
Toxicology (2nd revised ed.). New York, NY: Interscience Publishers.
Pearson. RG. (1990). Hard and soft acids and bases - the evolution of a chemical concept. Coord
Chem Rev 100: 403-425. http://dx.doi.org/10.1016/0010-8545(90)85016-L
Porter. LM; Jones. AR. (1995). Inhibition of glyceraldehyde 3- phosphate dehydrogenase in boar
spermatozoa by bromohydroxypropanone. Reprod Fertil Dev 7: 107-111.
http://dx.doi.org/10.1071/RD9950107
Oin. JZ; Xin. H; Nickoloffi BJ. (2010). 3-Bromopyruvate indices necrotic cell death in sensitive
melanoma cell lines. Biochem Biophys Res Commun 396: 495-500.
http://dx.doi.Org/10.1016/i.bbrc.2010.04.126
Page 367 of 486
-------
Raymond. LW; Ford. MP. (2007). Severe illness in furniture makers using a new glue: 1-
bromopropane toxicity confounded by arsenic. J Occup Environ Med 49: 1009-1019.
http://dx.doi.org/10.1097/JQM.0b013e318145b616
Reh. CM: Mortimer. YD: Nemhauser. JB; Trout. D. (2002). NIOSH Health Hazard Evaluation
Report: HETANo. 98-0153-2883, Custom Products, Inc. Mooresville, NC (pp. pp.).
(NTIS/02928129). Cincinnati, OH: National Board of Labour Protection (Finland).
http://www.cdc.gov/niosh/hhe/reports/pdfs/1998-0153-2883.pdf
Reh. CM: Nemhauser. JB. (2001). Health Hazard Evaluation Report: HETA 2000-0233-2845,
Trilithic, Inc. Indianapolis, Indiana. (NTIS/02937573_a). Organisation for Economic
Cooperation and Development (OECD).
Reyes. L; Manalich. R. (2005). Long-term consequences of low birth weight [Review], Kidney Int
Suppl 68: S107-S111. http://dx.doi.org/10.111 l/i.l523-1755.2005.09718.x
Saito-Suzuki. R; Teramoto. S: Shirasu. Y. (1982). Dominant lethal studies in rats with 1,2-
dibromo-3-chloropropane and its structurally related compounds. Mutat Res Genet Toxicol
101: 321-327. http://dx.doi.org/10.1016/0165-1218(82N)90125-2
Sakuratani. Y; Yamada. J: Kasai. K; Noguchi. Y; Nishihara. T. (2005). External validation of the
biodegradability prediction model CATABOL using data sets of existing and new
chemicals under the Japanese Chemical Substances Control Law. 16: 403-431.
http://dx.doi.org/10.1080/1065936050032Q289
Samukawa. M; Ichihara. G: Oka. N: Kusunoki. S. (2012). A case of severe neurotoxicity
associated with exposure to 1-bromopropane, an alternative to ozone-depleting or global-
warming solvents. Arch Intern Med 172: 1257-1260.
http: //dx. doi.org/10.10 01 /archi nternmed.2012.3987
Sclar. G. (1999). Encephalomyeloradiculoneuropathy following exposure to an industrial solvent.
Clin Neurol Neurosurg 101: 199-202. httD://dx.doi.org/10.1016/S0303-8467(99V)0034-7
Sebroski. JMM. (2017). Developing consensus standards for measuring chemical emissions from
spray polyurethane foam (SPF) insulation. Washington, DC: ASTM International.
http://dx.doi.org/10.1520/STP1589-EB
Sekiguchi. S: Suda. M; Zhai. YL; Honma. T. (2002). Effects of 1-bromopropane, 2-bromopropane,
and 1,2-dichloropropane on the estrous cycle and ovulation in F344 rats. Toxicol Lett 126:
41-49. http://dx.doi.org/10.1016/S0378-4274(01 ^>00429-5
Shochat. E; Hermoni. I: Cohen. Z; Abeliovich. A: Belkin. S. (1993). Bromoalkane-degrading
Pseudomonas strains. Appl Environ Microbiol 59: 1403-1409.
Simmon. VF; Kauhanen. K; Tardiff. RG. (1977). Mutagenic activity of chemicals identified in
drinking water. In D Scott; B Bridges; F Sobel (Eds.), Developments in Toxicology and
Environmental Science, 2 (pp. 249-258). New York, NY: Elsevier/North Holland Press.
Sohn. YK; Suh. JS: Kim. JW: Seo. HH: Kim. JY: Kim. HY: Lee. JY: Lee. SB: Han. JH: Lee. YM:
Lee. JY. (2002). A histopathologic study of the nervous system after inhalation exposure of
1-bromopropane in rat. Toxicol Lett 131: 195-201. http://dx.doi.org/10.1016/SQ378-
4274(02^00051-6
Stellies. M; Young. R; Weinberg. J. (2019). A 28-day somatic gene mutation study of 1-
bromopropane in female Big Blue® B6C3F1 mice via whole-body inhalation: Support for a
carcinogenic threshold. Regul Toxicol Pharmacol 104: 1-7.
Page 368 of 486
-------
Stewart. (1998). Airborne exposure assessment of 1-bromopropane (Sanitized). Stewart.
S ub ram an i an. K; Mohideen. SS; Suzumura. A; Asai. N; Murakumo. Y; Takahashi. M; Jin. S;
Zhang. L; Huang. Z; Ichihara. S; Kitoh. J; Ichihara. G. (2012). Exposure to 1-
bromopropane induces microglial changes and oxidative stress in the rat cerebellum.
Toxicology 302: 18-24. http://dx.doi.Org/10.1016/i.tox.2012.07.006
Suda. M; Honma. T; Miyagawa. M; Wang. RS. (2008). Alteration of brain levels of
neurotransmitters and amino acids in male F344 rats induced by three-week repeated
inhalation exposure to 1-bromopropane. Ind Health 46: 348-359.
http: //dx. doi. or g/10.2486/indhealth.46.348
Suter. G. (2016). Weight of evidence in ecological assessment. (EPA100R16001). Washington,
DC: U.S. Environmental Protection Agency.
https://cfpub.epa.gov/si/si public record report.cfm?dirEntryId=335523
Tachizawa. H; MacDonald. TL; Neal. RA. (1982). Rat liver microsomal metabolism of propyl
halides. Mol Pharmacol 22: 745-751.
Tech Spray. (2003). nPB and aerosol exposure. Tech Spray, L.P. Management.
http://www.regulations.gov/#!documentDetail;D=EPA-HO-OAR-2002-0064-0044
Thapa. P: Kim. EK: Nepal. MR: Jeong. KS: Kang. MJ: Noh. K: Lee. S: Jeong. HG: Lee. JH:
Jeong. TC: Lee. ES. (2016). Identification of a N7-guanine adduct of 1-bromopropane in
calf thymus DNA by mass spectrometry. Mol Cell Toxicol 12: 7-14.
http://dx.doi. org/10.1007/s 13273 -016-0002-5
Thomas. AP; Halestrap. AP. (1981). Identification of the protein responsible for pyruvate transport
into rat liver and heart mitochondria by specific labelling with [3H]N-phenylmaleimide.
Biochem J 196: 471-479.
Toraason. M; Lynch. DW: Debord. DG: Singh. N: Krieg. E; Butler. MA: Toennis. CA;
Nemhauser. JB. (2006). DNA damage in leukocytes of workers occupationally exposed to
1-bromopropane. Mutat Res Genet Toxicol Environ Mutagen 603: 1-14.
http://dx.doi.Org/10.1016/i.mrgentox.2005.08.015
Trafalis. DT; Panteli. ES: Grivas. A: Tsigris. C: Karamanakos. P. (2010). CYP2E1 and risk of
chemically mediated cancers [Review], Expert Opin Drug Metab Toxicol 6: 307-319.
http://dx.doi.org/10.1517/17425250903540238
TURI. (2012). Assessment of alternatives to the perchloroethylene for dry cleaning industry.
Available online at
http://www.turi.org/TURI Publications/TURI Methods Policy Reports/Assessment of A
lternatives to Perchloroethylene for the Dry Cleaning Industry. 2012
U.S. BLS. (2016). May 2016 Occupational Employment and Wage Estimates: National Industry-
Specific Estimates [Website], http://www.bls.gov/oes/tables.htm
U.S. BLS. (2017). Labor Force Statistics from the Current Population Survey. Current Population
Survey (CPS) Tables. Annual averages. Characteristics of the Employed. Table 14 and 18b.
Retrieved from https://www.bls.gov/cps/tables.htm
U.S. EPA. (1977). Control of volatile organic emissions from solvent metal cleaning [EPA
Report], (EPA-450/2-77-022). Research Triangle Park, NC: U.S. Environmental Protection
Agency, Office of Air and Waste Management, Office of Air Quality Planning and
Standards.
Page 369 of 486
-------
U.S. EPA. (1981). AP-42. Compilation of air pollutant emission factors. Chapter 4. 6: Solvent
degreasing. Washington, DC. http://www3.epa.gov/ttn/chief/ap42/ch04/final/c4s06.pdf
U.S. EPA. (1988). Recommendations for and documentation of biological values for use in risk
assessment (pp. 1-395). (EPA/600/6-87/008). Cincinnati, OH: U.S. Environmental
Protection Agency, Office of Research and Development, Office of Health and
Environmental Assessment, http://cfpub.epa.gov/ncea/cfm/recordisplav.cfm?deid=34855
U.S. EPA. (1992). Dermal exposure assessment: Principles and applications (interim report) [EPA
Report], (EPA/600/8-91/01 IB). Washington, DC: Office of Health and Environmental
Assessment. http://cfpub.epa.gov/ncea/cfm/recordisplav.cfm?deid=12188
U.S. EPA. (1994). Methods for derivation of inhalation reference concentrations and application of
inhalation dosimetry [EPA Report], (EPA/600/8-90/066F). Research Triangle Park, NC:
U.S. Environmental Protection Agency, Office of Research and Development, Office of
Health and Environmental Assessment, Environmental Criteria and Assessment Office.
https://cfpub.epa.gov/ncea/risk/recordisplav.cfm?deid=71993&CFID=51174829&CFTOK
EN=25006317
U.S. EPA. (1997). Solvent Cleaning. Volume III, Chapter 6. pp. 6.2.1. Washington, DC.
http://www3.epa.gov/ttnchiel/eiip/techreport/volume03/iii06fin.pdf
U.S. EPA. (1998a). Guidelines for ecological risk assessment [EPA Report], (EPA/630/R-
95/002F). Washington, DC: U.S. Environmental Protection Agency, Risk Assessment
Forum, https://www.epa.gov/risk/guidelines-ecological-risk-assessment
U.S. EPA. (1998b). Guidelines for neurotoxicity risk assessment [EPA Report] (pp. 1-89).
(EPA/630/R-95/001F). Washington, DC: U.S. Environmental Protection Agency, Risk
Assessment Forum, http://www.epa.gov/risk/guidelines-neurotoxicitv-risk-assessment
U.S. EPA. (2001). Risk assessment guidance for superfund: Volume III - Part A, Process for
conducting probabilistic risk assessment [EPA Report], (EPA/540-R-02-002). Washington,
DC: U.S. Environmental Protection Agency, Office of Emergency and Remedial Response.
http://www2.epa.gov/sites/production/files/2015-09/documents/rags3adt complete.pdf
U.S. EPA. (2002). A review of the reference dose and reference concentration processes (pp. 1-
192). (EPA/630/P-02/002F). Washington, DC: U.S. Environmental Protection Agency,
Risk Assessment Forum, http://www.epa.gov/osa/review-reference-dose-and-reference-
concentration-processes
U.S. EPA. (2003). Protection of the stratospheric ozone: Listing of substances for ozone depleting
substances - n-propyl bromide. Fed Reg 68: 33284-33316.
U.S. EPA. (2005a). Guidelines for carcinogen risk assessment [EPA Report] (pp. 1-166).
(EPA/630/P-03/001F). Washington, DC: U.S. Environmental Protection Agency, Risk
Assessment Forum, http://www2.epa.gov/osa/guidelines-carcinogen-risk-assessment
U.S. EPA. (2005b). Supplemental guidance for assessing susceptibility from early-life exposure to
carcinogens [EPA Report], (EPA/630/R-03/003F). Washington, DC: U.S. Environmental
Protection Agency, Risk Assessment Forum.
https://www3.epa.gov/airtoxics/childrens supplement final.pdf
U.S. EPA. (2006a). Risk assessment for the halogenated solvent cleaning source category [EPA
Report], (EPA Contract No. 68-D-01-052). Research Triangle Park, NC: U.S.
Page 370 of 486
-------
Environmental Protection Agency, Office of Air Quality Planning and Standards.
http://www3.epa.gov/airtoxics/degrea/residrisk20Q8.pdf
U.S. EPA. (2006b). Significant new alternatives policy (SNAP) - Risk screen on substitutes for
ozone depleting substances for adhesive, aerosol solvent, and solvent cleaning applications.
Proposed substitute: n-Propyl bromide. In Office of Air and Radiation, Stratospheric
Protection Division. Washington DC.
http://hero.epa.gov/index.cfm?action=search.view&reference id=2991013U.S. EPA.
(2011). Exposure factors handbook: 2011 edition (final) [EPA Report], (EPA/600/R-
090/052F). Washington, DC: U.S. Environmental Protection Agency, Office of Research
and Development, National Center for Environmental Assessment.
http://cfpub. epa.gov/ncea/cfm/recordisplav. cfm?deid=236252
U.S. EPA. (2012a). Benchmark dose technical guidance. (EPA/100/R-12/001). Washington, DC:
U.S. Environmental Protection Agency, Risk Assessment Forum.
https://www.epa.gov/risk/benchmark-dose-technical-guidance
U.S. EPA. (2012b). Estimation Programs Interface Suite for Microsoft Windows, v. 4.11.
https://www.epa.gov/tsca-screening-tools/download-epi-suitetm-estimation-program-
interface-v411
U.S. EPA. (2012c). Estimation Programs Interface Suite™ for Microsoft® Windows, v 4.11
[Computer Program], Washington, DC. Retrieved from https://www.epa.gov/tsca-
screening-tools/epi-suitetm-estimation-program-interface
U.S. EPA. (2012d). Non-Confidential 2012 Chemical Data Reporting.
http://www.epa.gov/oppt/cdr/pubs/guidance/lst CDR basics factsheet 5 23 2014.pdf
U.S. EPA. (2012e). Sustainable futures P2 framework manual [EPA Report], (EPA-748-B12-001).
Washington DC. http://www.epa.gov/sustainable-futures/sustainable-futures-p2-
framework-manual
U.S. EPA. (2013a). ChemSTEERuser guide - Chemical screening tool for exposures and
environmental releases. Washington, D.C. https://www.epa.gov/sites/production/files/2015-
05/documents/user guide.pdf
U.S. EPA. (2013b). Interpretive assistance document for assessment of discrete organic chemicals.
Sustainable futures summary assessment [EPA Report], Washington, DC.
http://www.epa.gov/sites/production/files/2015-05/documents/05-
iad discretes iune2013.pdf
U.S. EPA. (2013c). Use and market profile for 1-bromopropane in vapor degreasers, spray
adhesives, and aerosol solvents [EPA Report], Washington, DC.
U.S. EPA. (2014a). Degreasing with TCE in commercial facilities: Protecting workers [EPA
Report], Washington, DC: U.S. Environmental Protection Agency, Office of Pollution
Prevention and Toxics.
http://hero.epa.gov/index.cfm?action=search.view&reference id=4565445U.S. EPA.
(2014c). TSCA work plan chemical risk assessment. Trichloroethylene: Degreasing, spot
cleaning and arts & crafts uses. (740-R1-4002). Washington, DC: Environmental Protection
Agency, Office of Chemical Safety and Pollution Prevention.
http://www2.epa.gov/sites/production/files/2015-
09/documents/tce opptworkplanchemra final 062414.pdf
Page 371 of 486
-------
U.S. EPA. (2016a). Public database 2016 chemical data reporting (May 2017 release). Washington,
DC: US Environmental Protection Agency, Office of Pollution Prevention and Toxics.
Retrieved from https://www.epa.gov/chemical-data-reporting
U.S. EPA. (2016b). TRI Basic Plus Data Files: 2016 Reporting Year (Version 15). Retrieved from
https://www.epa.gov/toxics-release-inventorv-tri-program/tri-basic-plus-data-files-
calendar-years-1987-2017
U.S. EPA. (2016c). TSCA work plan chemical risk assessment: Peer review draft 1-bromopropane:
(n-Propyl bromide) spray adhesives, dry cleaning, and degreasing uses CASRN: 106-94-5
[EPA Report], (EPA 740-R1-5001). Washington, DC.
https://www.epa.gov/sites/production/files/2016-03/documents/l-
bp report and appendices final.pdf
U.S. EPA. (2017a). Chemical data reporting: 1-bromo-propane [Database], Retrieved from
http://i ava.epa. gov/chemview
U.S. EPA. (2017b). Preliminary Data for 2017 Reporting Year.
U.S. EPA. (2017c). Preliminary Information on Manufacturing, Processing, Distribution, Use, and
Disposal: 1-Bromopropane. Support document for Docket EPA-HQ-OPPT-2016-0741
[Comment], (EPA-HQ-OPPT-2016-0741-0003). Washington, DC: Office of Chemical
Safety and Pollution Prevention, https://www.epa.gov/sites/production/files/2017-
02/documents/1 -bromopropane.pdf
U.S. EPA. (2017d). Scope of the risk evaluation for 1-Bromopropane [EPA Report], (EPA- 740-
Rl-7009). https://www.epa.gov/sites/production/files/2017-06/documents/bp scope 06-22-
17.pdf
U.S. EPA. (2017e). Strategy for conducting literature searches for 1-Bromopropane (1-bp):
supplemental document to the TSCA scope document [EPA Report],
https://www.epa.gov/sites/production/files/2017-06/documents/l-
bp lit search strategy 053017 O.pdf
U.S. EPA. (2017f). Toxics Release Inventory (TRI), reporting year 2015. Retrieved from
https://www.epa.gov/toxics-release-inventorv-tri-program/tri-data-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/production/files/2018-
06/documents/final application of sr in tsca 05-31-18.pdf
U.S. EPA. (2018c). Problem formulation of the risk evaluation for 1-bromopropane. (EPA-740-R1-
7019). Washington, DC: Office of Chemical Safety and Pollution Prevention, United States
Environmental Protection Agency, https://www.epa.gov/sites/production/files/2018-
06/documents/lbp problem formulation 05-31-18.pdf
U.S. EPA. (2018d). Strategy for assessing data quality in TSCA risk evaluations. Washington DC:
U.S. Environmental Protection Agency, Office of Pollution Prevention and Toxics.
U.S. EPA. (2019a). Consumer Exposure Model (CEM) 2.1 User Guide. (EPA Contract # EP-W-
12-010). Washington, DC.
U.S. EPA. (2019b). Consumer Exposure Model (CEM) 2.1 User Guide - Appendices. (EPA
Contract # EP-W-12-010). Washington, DC: U.S. EPA.
Page 372 of 486
-------
U.S. EPA. (2019c). IECCU 1.1 User's Guide. In Simulation Program for Estimating Chemical
Emissions from Sources and Related Changes to Indoor Environmental Concentrations in
Buildings with Conditioned and Unconditioned Zones (IECCU). (EPA Contract # EP-W-
12-010). Washington, DC: U.S. Environmental Protection Agency, Office of Pollution
Prevention and Toxics.
U.S. EPA. (2019d). Multi-Chamber Concentration and Exposure Model (MCCEM) User Guide.
U.S. EPA.
U.S. EPA; ICF Consulting. (2004). The U.S. solvent cleaning industry and the transition to non
ozone depleting substances. http://www.hsia.org/applications/ODS%20report.pdf
Ueno. S: Yoshida. Y; Fueta. Y; Ishidao. T; Liu. J: Kunugita. N: Yanagihara. N: Hori. H. (2007).
Changes in the function of the inhibitory neurotransmitter system in the rat brain following
subchronic inhalation exposure to 1-bromopropane. Neurotoxicology 28: 415-420.
http://dx.doi.Org/10.1016/i.neuro.2006.03.006
Valentine. H; Amarnath. K; Amarnath. V; Li. WH; Ding. XC: Valentine. WM; Ichihara. G. (2007).
Globin S-Propyl Cysteine and urinary N-acetyl-S-propylcysteine as internal biomarkers of
1-bromopropane exposure. Toxicol Sci 98: 427-435.
http://dx.doi.org/10.1093/toxsci/kfml26
Van Raaii. MTM; Janssen. PAH: Piersma. AH. (2003). The relevance of developmental toxicity
endpoints for acute limits settings (pp. 1-88). (RIVM Report 601900004). Nederlands:
Nederlands National Institute for Public Health and the Environment.
http://www2.epa.gov/sites/production/files/2014-04/documents/mtg35b.pdf
Von Grote. J: Hurlimann. JC: Scheringer. M; Hungerbuhler. K. (2003). Reduction of Occupational
Exposure to Perchloroethylene and Trichloroethylene in Metal Degreasing over the Last 30
years: Influence of Technology Innovation and Legislation. J Expo Anal Environ
Epidemiol 13: 325-340. http://dx.doi.org/10.1038/si.iea.7500288
Wadden. RA; Scheff. PA: Franke. JE. (1989). Emission Factors for Trichloroethylene Vapor
Degreasers. Am Ind Hyg Assoc J 50: 495-500.
Wang. H; Ichihara. G: Ito. H; Kato. K; Kitoh. J: Yamada. T; Yu. X: Tsuboi. S: Moriyama. Y;
Sakatani. R; Shibata. E; Kamijima. M; Itohara. S: Takeuchi. Y. (2002). Biochemical
changes in the central nervous system of rats exposed to 1-bromopropane for seven days.
Toxicol Sci 67: 114-120. http://dx.doi.Org/10.1093/toxsci/67.l.l 14
Wang. H; Ichihara. G: Ito. H; Kato. K; Kitoh. J: Yamada. T; Yu. X: Tsuboi. S: Moriyama. Y;
Takeuchi. Y. (2003). Dose-dependent biochemical changes in rat central nervous system
after 12-week exposure to 1-bromopropane. Neurotoxicology 24: 199-206.
http://dx.doi.org/10.1016/S0161-813X(02X)0195-X
Wang. OH: Zhong. ZX; Chen. JJ; Xie. KQ; Zhao. XL. (2012). [Development of peripheral
neuropathy rat model induced by 1-bromopropane], Zhonghua Laodong Weisheng
Zhiyebing Zazhi 30: 751-755.
Weinberg. JT. (2016). A 28-day somatic gene mutation study of 1-bromopropane in female Big
Blue® B6C3F1 mice via whole-body inhalation. (Laboratory Project ID WIL-266501).
Melrose Park, IL, US: Enviro Tech International.
Page 373 of 486
-------
Wheeler. MW; Bailer. AJ. (2007). Properties of model-averaged BMDLs: A study of model
averaging in dichotomous response risk estimation. Risk Anal 27: 659-670.
http://dx.doi.org/10.1111/i. 1539-6924.2007.00920.X
Whittaker. C: Rice. F; McKernan. L; Dankovic. D; Lentz. T; Macmahon. K; Kuempel. E;
Zumwalde. R; Schulte. P. (2016). Current Intelligence Bulletin 68: NIOSH Chemical
Carcinogen Policy. US Department of Health and Human Services.
https://ntrl.ntis. gov/NTRL/dashboard/ searchResults/titleDetail/PB2017101413 .xhtml
Whittaker. SG: Johanson. CA. (2011). A profile of the dry cleaning industry in King County,
Washington: Final report. (LHWMP 0048). Seattle, WA: Local Hazardous Waste
Management Program in King County.
http://www.hazwastehelp.org/publications/publications detail.aspx?DocID=Oh73%2fOilg9
0%3d
WIL Research. (2001). An inhalation two-generation reproductive toxicity study of 1-
bromopropane in rats. (Study No. WIL-3 80001). Ashland, OH.
Woo. YT; Lai. DY. (2003). Mechanism of action of chemical carcinogenes and their role in
Structure-Activity Relationship (SAR) analysis and risk assessment. In R Benigni (Ed.),
(pp. 41-80). Boca Raton, FL: CRC Press.
Xin. OO: Huang. Y: Li. J: Zhang. WJ: Yu. T: Wang. H: Zhang. C: Ye. DO: Huang. F. (2010).
Apoptosis contributes to testicular toxicity induced by two isomers of bromopropanes.
Toxicol Ind Health 26: 513-524. http://dx.doi.org/10.1177/0748233710373083
Yahagi. T; Nagao. M; Seino. Y; Matsushima. T; Sugimura. T. (1977). Mutagenicities of N-
nitrosamines on Salmonella. MutatRes 48: 121-129.
Yalkowsky. SH; He. Y; Jain. P. (2010). Handbook of aqueous solubility data (2nd ed.). Boca
Raton, FL: CRC Press. http://dx.doi.org/10.1201/EBK1439802458
Yamada. T; Ichihara. G: Wang. H; Yu. X: Maeda. K; Tsukamura. H; Kamijima. M; Nakaiima. T;
Takeuchi. Y. (2003). Exposure to 1-bromopropane causes ovarian dysfunction in rats.
Toxicol Sci 71: 96-103. http://dx.doi.Org/10.1093/toxsci/71.l.96
Yoshida. Y; Liu. JO: Nakano. Y; Ueno. S: Ohmori. S: Fueta. Y; Ishidao. T; Kunugita. N:
Yamashita. U: Hori. H. (2007). 1-BP inhibits NF-kappaB activity and Bcl-xL expression in
astrocytes in vitro and reduces Bcl-xL expression in the brains of rats in vivo.
Neurotoxicology 28: 381-386. http://dx.doi.Org/10.1016/i.neuro.2006.05.015
Young. ML. (2012). Pre-spotting step toward better cleaning. Available online at
https://americandrvcleaner.com/articles/pre-spotting-step-toward-better-cleaning
Young. RR. (2016). In vivo mutation assay of n-propyl bromide at the ell locus in Big Blue®
transgenic B6C3F1 mice exposed via whole-body inhalation. Provided by Julie Ownbey,
ICL Industrial Products. Beer-Sheva, Israel: ICL-IP.
Yu. WJ: Kim. JC: Chung. MK. (2008). Lack of dominant lethality in mice following 1-
bromopropane treatment. Mutat Res Genet Toxicol Environ Mutagen 652: 81-87.
http://dx.doi.Org/10.1016/i.mrgentox.2008.01.001
Yu. X: Ichihara. G: Kitoh. J: Xie. Z; Shibata. E; Kamijima. M; Takeuchi. Y. (2001). Neurotoxicity
of 2-bromopropane and 1-bromopropane, alternative solvents for chlorofluorocarbons.
Environ Res 85: 48-52. http://dx.doi.org/10.1006/enrs.200Q.4226
Page 374 of 486
-------
Zhang. L; Nagai. T; Yamada. K; Ibi. D; Ichihara. S; Subramanian. K; Huang. Z; Mohideen. SS;
Naito. H; Ichihara. G. (2013). Effects of sub-acute and sub-chronic inhalation of 1-
bromopropane on neurogenesis in adult rats. Toxicology 304: 76-82.
http://dx.doi.Org/10.1016/i.tox.2012.12.009
Zhang. ZW: Kawai. T; Takeuchi. A: Miyama. Y; Sakamoto. K; Watanabe. T; Matsuda-Inoguchi.
N: Shimbo. S: Higashikawa. K; Ikeda. M. (2001). Urinary bromide levels probably
dependent to intake of foods such as sea algae. Arch Environ Contam Toxicol 40: 579-584.
http://dx.doi. org/10.1007/s002440010213
Zhao. WY; Aoki. K; Xie. TX; Misumi. J. (1999). Electrophysiological changes induced by
different doses of 1-bromopropane and 2-bromopropane. J Occup Health 41: 1-7.
http://dx.doi.Org/10.1539/ioh.41.l
Zhong. Z; Zeng. T; Xie. K; Zhang. C: Chen. J: Bi. Y; Zhao. X. (2013). Elevation of 4-
hydroxynonenal and malondialdehyde modified protein levels in cerebral cortex with
cognitive dysfunction in rats exposed to 1-bromopropane. Toxicology 306: 16-23.
http://dx.doi.Org/10.1016/i.tox.2013.01.022
Zong. C: Garner. CE; Huang. C: Zhang. X: Zhang. L; Chang. J: Tovokuni. S: Ito. H; Kato. M;
Sakurai. T; Ichihara. S: Ichihara. G. (2016). Preliminary characterization of a murine model
for 1-bromopropane neurotoxicity: Role of cytochrome P450. Toxicol Lett 258: 249-258.
http://dx.doi.Org/10.1016/i.toxlet.2016.07.006
Page 375 of 486
-------
Appendix A REGULATORY HISTORY
A.l Federal Laws and Regulations
TableApx A-l. Federal Laws and Regulations
Statutes/Regulations
Description of Authority/Regulation
Description of Regulation
US EPA Regulations
Toxic Substances Control
Act (TSCA) - Section
6(b)
EPA is directed to identify and begin risk
evaluations on 10 chemical substances drawn
from the 2014 update of the TSCA Work Plan
for Chemical Assessments.
1-BP is on the initial list of chemicals to be
evaluated for unreasonable risk under TSCA
(81 FR 91927, December 19, 2016)
Toxic Substances Control
Act (TSCA) - Section
8(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 domestically and
imported into the US.
1-BP manufacturing, importing, processing,
and use information is reported under the
Chemical Data Reporting (CDR) rule (76 FR
50816, August 16, 2011).
Toxic Substances Control
Act (TSCA) - Section
8(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.
1-BP 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 enviromnent.
Eleven notifications of substantial risk
(Section 8(e)) received before 2001 (US EPA,
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.
One submission from a test rule (Section 4)
received in 1981 (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 10 or more
full time equivalent employees and that
manufacture, process, or otherwise use a Toxics
Release Inventory (TRI)-listed chemical in
quantities above threshold levels.
1-BP is a listed substance subject to reporting
requirements under 40 CFR 372.65 effective
as of January 1, 2016, with reporting due July
1, 2017 (80 FR 72906, November 23, 2015).'
Clean Air Act (CAA) -
Section 112(b)
The Clean Air Act (CAA) contains a list of
hazardous air pollutants (HAP) and provides
EPA with the authority to add to that list
pollutants that present, or may present, a threat of
adverse human health effects or adverse
environmental effects. For all major source
categories emitting HAP, the CAA requires
issuance of teclinology-based standards and, 8
years later, if necessary, additions or revisions to
address developments in practices, processes,
and control technologies, and to ensure the
standards adequately protect public health and
the enviromnent. The CAA thereby provides
EPA received petitions from the Halogenated
Solvent Industry Alliance and the New York
State Department of Environmental
Conservation to list 1-BP as a hazardous air
pollutant (HAP) under section 112(b)(1) of
the Clean Air Act (80 FR 6676, February 6,
2015). On January 9, 2017, EPA published a
draft notice on the rationale for granting the
petitions to add 1-BP to the list ofHAP The
public comment period closed on June 8,
2017 (82 FR 2354, January 9, 2017). On June
18, 2020, EPA granted the petition to add 1-
BP to the list ofHAP (85 FR 36851) and will
Page 376 of 486
-------
Statutes/Regulations
Description of Authority/Regulation
Description of Regulation
EPA with comprehensive authority to regulate
emissions to ambient air of any hazardous air
pollutant.
take a separate regulatory action to add 1-BP
to the list of HAP under CAA section
112(b)(1). Since 1-BP is not a HAP,
currently, there are no National Emissions
Standards for Hazardous Air Pollutants
(NESHAPs).
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 (NAAQS) 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
substantially as effective as regulations.
1-BP is listed under the National Volatile
Organic Compound Emission Standards for
Aerosol Coatings (40 CFR part 59, subpart
E). 1-BP has a reactivity factor of 0.35 g 03/g
VOC.
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 EPA's SNAP program, EPA evaluated
1-BP as an acceptable substitute for ozone-
depleting substances. In 2007, EPA listed 1-
BP as an acceptable substitute for
chlorofluorocarbon (CFC)-113 and methyl
chloroform in the solvent and cleaning sector
for metals cleaning, electronics cleaning, and
precision cleaning. EPA recommended the
use of personal protective equipment,
including chemical goggles, flexible laminate
protective gloves and chemical-resistant
clothing (72 FR 30142, May 30, 2007). In
2007, the Agency also proposed to list 1-BP
as an unacceptable substitute for CFC-113,
hydrochlorofluorocarbon (HCFC)- 114b and
methyl chloroform when used in adhesives or
in aerosol solvents; and in the coatings end
use (subject to use conditions) (72 FR 30168,
May 30, 2007). The proposed rule has not
been finalized by the Agency. The rule
identifies 1-BP as acceptable and
unacceptable substitute for ozone-depleting
substances in several sectors.
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.
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.
OSHA has not issued a PEL for 1-BP.
OSHA and the National Institute for
Occupational Safety and Health (NIOSH)
issued a Hazard Alert re sardine 1-BP
(OSHA-NIOSH, 2013) providing information
regarding health effects, how workers are
exposed, how to control the exposures and
how OSHA and NIOSH can help. The Hazard
Alert states that: "ACGIH currently
recommends a 10 ppm time-weighted average
threshold limit value but has proposed
lowering the value to 0.1 ppm [ACGIH
Page 377 of 486
-------
Statutes/Regulations
Description of Authority/Regulation
Description of Regulation
20131." OSHA also released an Enforcement
Policy for Respiratory Hazards Not Covered
bv OSHA Permissible Exposure Limits that
explain OSHA requirements and the
applicability of this policy pertaining to 1-BP
exposure limits under certain conditions.
Department of Energy
(DOE)
The Atomic Energy Act authorizes DOE to
regulate the health and safety of its contractor
employees.
10 CFR 851.23, Worker Safety and Health
Program, requires the use of the 2005 ACGIH
TLVs if they are more protective than the
OSHA PEL. The 2005 TLV for 1-BP is 10
ppm (8hr Time Weighted Average).
A.2 State Laws and Regulations
TableApx A-2. State Laws and Regulations
State Actions
Description of Action
State Air Regulations
Allowable Ambient Levels
Rhode Island (Air Pollution Regulation No. 22)
New Hampshire (Env-A 1400: Regulated Toxic Air Pollutants)
New York has a de facto ban on the use of 1-BP in dry cleaning. New York will not issue
an Air Facility Registration to any facility proposing to use that chemical as an alternative
dry cleaning solvent as it is not an approved alternative solvent.
Chemicals of High
Concern
Massachusetts designated 1-BP as a higher hazard substance requiring reporting starting
in 2016 (301 CMR 41.00).
Minnesota listed 1-BP as chemical of high concern to children (Minnesota Statutes
116.9401 to 116.9407).
State Permissible Exposure
Limits
California PEL: 5 ppm as an 8-hr-time-weighted average (TWA) (California Code of
Regulations, title 8, section 5155).
State Right-to-Know Acts
New Jersey (42 N.J.R. 1709(a)), Pennsylvania (Chapter 323. Hazardous Substance List).
Other
In California, 1-BP was added to proposition 65 list in December 2004 due to
developmental, female and male, toxicity; and in 2016 due to cancer. (Cal. Code Regs,
title 27, section 27001).
1-BP is listed as a Candidate Chemical under California's Safer Consumer Products
Program (Health and Safety Code sections 25252 and 25253).
California also selected 1-BP as the first chemical for early warning and prevention
activities under SB 193 Early Warning Authority and issued a Health Hazard Alert for 1 -
BP (Hazard Evaluation System and Information Service, 2016).
Oregon has adopted, and is considering, several state-specific statutes and regulations to
manage the impacts of toxic and hazardous pollutants, including air toxics permits and
benchmarks for industrial facilities, and the Toxics Use and Hazardous Waste Reduction
planning requirements, which apply to large and small quantity generators of hazardous
waste and Toxic Release Inventory reporters.
The District of Columbia's Hazardous Waste Management Act includes provisions for
toxic chemical source reporting and reduction. Businesses identified by the Standard
Industrial Classification (SIC) as the largest generators or within the top 25% of all
hazardous waste generators within the District, or that release a toxic chemical subject to
Page 378 of 486
-------
State Actions
Description of Action
regulation are required to file an annual Toxic Release Inventory (TRI) Form R for each
TRI-listed chemical it manufactures, processes or otherwise uses in quantities above the
threshold reporting quantity. In addition reporting facilities must prepare and submit a
toxic chemical source reduction plan which must be updated every four years.
A.3 International Laws and Regulations
TableApx A-3. Regulatory Actions by other Governments and Tribes
Country /Organization
Requirements and Restrictions
European Union
In 2012, 1-BP 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 due to its reproductive toxicity (category
IB).
In June 2017, 1-BP was added to Annex XIV of REACH (Authorisation List) with a
sunset date of July 4, 2020 (European Chemicals Agency (ECHA) database. Accessed
December 6, 2017).
Australia
1-BP was assessed under Enviromnent Tier II of the Inventory Multi-tiered Assessment
and Prioritisation (IMAP) (National Industrial Chemicals Notification and Assessment
Scheme (NICNAS), 2017, Human Health Tier II Assessment for Propane, 1-bromo-.
Accessed April, 18 2017).
Japan
1-BP is regulated in Japan under the following legislation:
Act on the Evaluation of Chemical Substances and Regulation of Their Manufacture, etc.
(Chemical Substances Control Law; CSCL)
Act on Confirmation, etc. of Release Amounts of Specific Chemical Substances in the
Enviromnent and Promotion of Improvements to the Management Thereof
Industrial Safety and Health Act (ISHA)
Air Pollution Control Law
(National Institute of Technology and Evaluation (NITE) Chemical Risk Information
Platform (CHIRP). Accessed April 13, 2017).
Belgium, Canada, Finland,
Japan, Poland, South
Korea and Spain
Occupational exposure limits for 1-BP. (GESTIS International limit values for chemical
agents (Occupational exposure limits, OELs) database. Accessed April 18, 2017).
Basel Convention
Halogenated organic solvents (Y41) are listed as a category of waste under the Basel
Convention - Annex I. Although the United States is not currently a party to the Basel
Convention, this treaty still affects U.S. importers and exporters.
OECD Control of
Transboundary Movements
of Wastes Destined for
Recovery Operations
Halogenated organic solvents (A3150) are listed as a category of waste subject to The
Amber Control Procedure under Council Decision C (2001) 107/Final.
Page 379 of 486
-------
Appendix B LIST OF SUPPLEMENTAL DOCUMENTS
List of supplemental documents:
Associated Systematic Review Data Quality Evaluation Documents - Provides additional detail
and information on individual study evaluations including criteria and scoring results.
1. Final Risk Evaluation for 1-Bromopropane (1-BP), Systematic Review Supplemental File:
Updates to Data Quality Criteria for Epidemiological Studies. (EPA. 2019ci).
2. Final Risk Evaluation for 1-Bromopropane (1-BP), Systematic Review Supplemental File:
Data Quality Evaluation of Environmental Fate and Transport Studies. (EPA. 20191).
3. Final Risk Evaluation for 1-Bromopropane (1-BP), Systematic Review Supplemental File:
Data Quality Evaluation for Consumer Exposure. (EPA. 2019i). .
4. Final Risk Evaluation for 1-Bromopropane (1-BP), Systematic Review Supplemental File:
Data Quality Evaluation for Release and Occupational Exposure. (EPA. 2019m).
5. Final Risk Evaluation for 1-Bromopropane (1-BP), Systematic Review Supplemental File:
Data Quality Evaluation for Release and Occupational Exposure - Common Sources. (EPA.
2019n).
6. Final Risk Evaluation for 1-Bromopropane (1-BP), Systematic Review Supplemental File:
Data Quality Evaluation of Ecological Hazard Study. (EPA. 2019k).
7. Final Risk Evaluation for 1-Bromopropane (1-BP), Systematic Review Supplemental File:
Data Quality Evaluation of Human Health Hazard Studies - Epidemiologic Studies. (EPA.
2019p).
8. Final Risk Evaluation for 1-Bromopropane (1-BP), Systematic Review Supplemental File:
Data Quality Evaluation of Human Health Hazard Studies - Animal and In Vitro Studies.
EPA-HQ-OPPT-2019-023 5 (EPA. 2019o).
9. Final Risk Evaluation for 1-Bromopropane (1-BP), Systematic Review Supplemental File:
Data Extraction Tables for Environmental Fate and Transport Studies. (EPA. 2019i).
10. Final Risk Evaluation for 1-Bromopropane (1-BP), Systematic Review Supplemental File:
Data Extraction for Consumer Exposure. (EPA. 2019h).
11. Final Risk Evaluation for 1-Bromopropane (1-BP), Systematic Review Supplemental File:
Data Quality Evaluation of Physical-Chemical Property Studies. (U.S. EPA. 2019)
Associated Supplemental Information Documents - Provides additional details and information on
engineering and exposure assessments.
1. Final Risk Evaluation for 1-Bromopropane (1-BP), Supplemental File: Information on
Consumer Exposure Assessment Model Input Parameters. (EPA. 2019a).
2. Final Risk Evaluation for 1-Bromopropane (1-BP), Supplemental File: Information on
Consumer Exposure Assessment Model Outputs. (EPA. 2019b).
3. Final Risk Evaluation for 1-Bromopropane (1-BP), Supplemental File: Consumer Exposure
Risk Calculations. (EPA. 2019c).
Page 380 of 486
-------
4. Final Risk Evaluation for 1-Bromopropane (1-BP), Supplemental File: Information on
Occupational Exposure Assessment (EPA. 2019f). This document provides additional
details and information on the occupational exposure assessment, including estimates of
number of sites and workers, summary of monitoring data, and exposure modeling
equations, inputs and outputs.
5. Final Risk Evaluation for 1-Bromopropane (1-BP), Supplemental File: Occupational Risk
Calculator. (EPA. 2019g).
6. Final Risk Evaluation for 1-Bromopropane (1-BP), Supplemental File: Human Health
Benchmark Dose Modeling. (EPA. 2019d).
Page 381 of 486
-------
Appendix C FATE AND TRANSPORT
C.l Fate in Air
If released to the atmosphere, 1-BP is expected to exist solely in the vapor-phase based on its vapor
pressure. In the vapor phase, it is degraded by reaction with photochemically produced hydroxyl
radicals. The half-life of this reaction is approximately 9-12 days assuming a hydroxyl radical
concentration over a 12 hour day of 1.5><106 hydroxyl radicals per cubic centimeter of air (Version
4.10 EPISuite). Its atmospheric degradation and its photooxidation products were investigated for
their ozone depletion potential (Burkholder et al.. 2002). It was shown that the hydroxyl radical
initiated degradation does not lead to long-lived bromine containing species that can migrate to the
stratosphere. The major photodegradation products were bromoacetone, propanal and 3-
bromopropanal. Bromoacetone was rapidly photolyzed releasing bromine which was removed
from the atmosphere by wet deposition. 1-BP does not absorb light greater than 290 nm; therefore,
degradation of this substance by direct photolysis is not expected to be an important fate process.
The bromoacetone and propanal constitute about 90% of 1-BP that is degraded in the atmosphere,
and they, as well as 3-bromopropanal, are expected to be rapidly degraded. Apparently, the major
atmospheric degradative fate of 1-BP is the rapid and irreversible release of Br atoms. Based on the
1-BP estimated half-life of 9-12 days in air, it is possible that it can undergo long range transport
via the atmosphere.
€.2 Fate in Water
When released to water, 1-BP is not expected to sorb to suspended solids and sediment in the water
column based upon its estimated Koc value of about 40 (U.S. EPA. 2013b). The rate of
volatilization is expected to be rapid based on a Henry's Law constant of 7.3 x 10"3 atm-m3/mole.
1-BP was reported to achieve 70% of its theoretical biochemical oxygen demand (BOD) in the
MITI (OECD 301C) test (Sakuratani et al.. 2005) which is considered readily biodegradable.
Bacterial strains isolated from organobromide-rich industrial wastewater were shown to degrade 1-
BP (Shochat et al.. 1993). Arthrobacter HA1 debrominated 1-BP under aerobic conditions yielding
1-propanol as a degradation product (Belkin. 1992) and Acinetobacter strain GJ70, isolated from
activated sludge was able to utilize it as a carbon source (Janssen et al.. 1987). These results
suggest that 1-BP will undergo biodegradation in the environment under aerobic conditions.
Hydrolysis of 1-BP is expected based on studies of (Mabev and Mill. 1978). A hydrolysis half-life
of about 26 days was calculated at pH 7 and 25 degrees Celsius from its first-order neutral rate
constant of 3.01><10"7 sec"1. The expected hydrolysis product is propanol and the
hydrodebromination product propene is also possible. Photooxidation in water has not been
reported to be an important environmental fate process. 1-BP is not expected to be persistent in
water.
Page 382 of 486
-------
€.3 Fate in Sediment and Soil
l-BP is expected to have high mobility in soil based on an estimated log Koc of 1.6. Volatilization
is expected to be an important fate process given its relatively high Henry's law constant of 7.3x10
3 atm m3/mole. Its biodegradation is considered to be moderate in sediment and soil. l-BP is not
persistent in sediment or soil.
Page 383 of 486
-------
Appendix D CHEMICAL DATA REPORTING RULE DATA
FOR 1-BP
EPA's 2012 Chemical Data Reporting (CDR.) reported a 1-BP production volume of 15.4 million
pounds. Albemarle Corporation and a CBI company reported domestic manufacturing of 1-BP
(U.S. EPA 2012d). Dow Chemical Company, Special Materials Company, and ICL reported
imports of 1-BP (U.S. EPA 2012d). Data in TableApx D-l through TableApx D-3 were
extracted from the 2012 CDR records (U.S. EPA 2012d).
Table Apx D-l. National Chemical Information for 1-BP from 2012 CDR
Production Volume (aggregate)
15.4 million pounds
Maximum Concentration (at manufacture or import site)
>90%
Physical fonn(s)
Liquid
Number of reasonably likely to be exposed industrial manufacturing, processing,
and use workers (aggregated)
>1,000
Was industrial processing or use information reported?
Yes
Was commercial or consumer use information reported?
Yes
Table Apx D-2. Summary of Industrial 1-BP Uses from 2012 CDR
Industrial Sector
(Based on NAICS)
Industrial Function
Type of Processing
Soap, Cleaning Compound, and
Toilet Preparation
Manufacturing
Solvents (for cleaning or
degreasing)
Processing-repackaging
Soap, Cleaning Compound, and
Toilet Preparation
Manufacturing
Solvents (for cleaning or
degreasing)
Processing-incorporation
Abbreviations: NAICS=North American Industry Classification System
Table Apx D-3. Commercial/Consumer Use Category Summary of 1-BP
Commercial/Consumer Product
Category
Intended for Commercial and/or
Consumer Uses or Both
Intended for Use in Children's
Products in Related Product
Category
Cleaning and Furnishing Care
Products
Commercial
No
Electrical and Electronic
Products
Commercial
No
Page 384 of 486
-------
Appendix E EXPERIMENTAL MEASUREMENT OF
FRACTION ABSORBED FOR DERMAL
EXPOSURE MODELING
Section 2.3.1.23 presents EPA's modeling approach to estimate dermal exposure in occupational
scenarios. The Dermal Exposure to Volatile Liquids Model (Equation 2-2) calculates the dermal
retained dose by incorporating a "fraction absorbed (fabs)" parameter to account for the evaporation
of volatile chemicals. This parameter can either be estimated (using steady-state approximation) or
measured. This appendix discusses measured experimental value of fabs used in the 1-BP Risk
Evaluation.
In a 2011 study, Frasch et al. tested dermal absorption characteristics of 1-BP. For the finite dose
scenario, Frasch et al. (2011) determined that unoccluded exposure resulted in a fractional
absorption of 0.16 percent of applied 1-BP. The measurement was performed in an open fume
hood with an average air speed of 0.3 m/s (30 cm/s) - a value likely higher than typical air velocity
that workers would experience indoors. Because higher air velocity increases the rate of chemical
evaporation, the experimental value likely underestimates fractional absorption. As such, this
measured value should be adjusted to account for typical environmental conditions relevant to
worker exposures.
Fraction absorbed (0
-------
EquationApx E-3. Gas-Phase Mass Transfer Coefficient
6320 ¦ u0-78
kg ~ MW1/3
Where:
kg is the gas-phase mass transfer coefficient
Pvap is the vapor pressure at the temperature of the liquid
R is the gas constant
T is temperature
u is wind speed
MW is molecular weight
Equation Apx E-l through Equation Apx E-3 demonstrate that the evaporative flux Wp is a
function of wind speed (u) to the 0.78 power.
E.2 Experimental Wind Speed Measurements
Baldwin and Maynard (1998) measured indoor air speeds across 55 workplaces in the United
Kingdom. These workplaces cover both industrial and commercial facilities. The authors suggest
indoor wind speed data could be approximated by a lognormal distribution. Figure Apx E-l fits
the wind speed measurements to a lognormal distribution. The fitted distribution has a mean of
17.6 cm/s and a standard deviation of 18.4 cm/s. The lower bound of the distribution is set to zero.
The 50th percentile wind speed within this distribution is 12.2 cm/s. Approximately 85 percent of
the distribution are below 30 cm/s (0.3 m/s), the wind speed noted by Frasch et al. (2011) during
the 1-BP evaporative flux measurement.
Page 386 of 486
-------
0.06
0.05
0.04
0.03
0.02
0.01
0.00 1
Measured
Indoor Wind
Speed
O
O
o
r\j
o
o
o
oo
o
o
r\j
Mean Indoor Wind Speed (cm/s)
FigureApx E-l. Distribution of Mean Indoor Wind Speed as Measured by Baldwin and
Maynard (1998)
E.3 Adjusting x and fabs for Wind Speed
In the 1-BP in vitro dermal penetration study, Frasch et al. (2011) measured an evaporative flux
(Jevap) of 470 mg/cm2-h. The experimentally measured steady-state absorption flux (Jmax.ss) ranges
from 625 to 960 [j,g/cm2-h (infinite-dose, neat 1-BP). The evaporative flux was measured at 23°C,
whereas the absorption flux was measured near the typical skin surface temperature of 32°C.
From the relationship given in EquationApx E-l through EquationApx E-3, the adjusted
evaporative flux (J'eVap) can be calculated as:
Equation Apx E-4. Adjusted Dermal Evaporative Flux
/'
evap
~ Jevap I _.
, . 0-7S /n
U \ (P,
u
vap 1
, Pvap T';
1-BP has a vapor pressure of 110.8 mmHg at 20°C (293K). At the skin surface temperature of 32°C
(T' = 305K), the adjusted vapor pressure can be calculated using the Clausius-Clapeyron equation:
Equation Apx E-5. Adjusted Vapor Pressure
In I
[ vap
[ vap ,
AH,
vap
R
\T T'J
Page 387 of 486
-------
/ Pvap' \ 32,130 J/mol / 1 1 \
71VI 10.8 mmHgy ~ 8.314 J/mol-K V20 + 273 T + 273/
If T' = 23°C (296K), PVaP' = 126.6 mmHg
If T' = 32°C (305K), PVaP' = 186.2 mmHg
At the 50th percentile wind speed measured by Baldwin and Maynard (1998) (u' = 12.2 cm/s), the
adjusted evaporative flux is:
, mg /12.2 cm/s\0,78 /186.2 mmHg 296K\ mg
J evap 470 ^2 ^ V 30 cm/s / V126.6 mmHg 305K/ ^^^cm2-h
From Equation Apx E-l and the steady-state approximation for fraction absorbed (fabs):
1
/ ' 1
J evap _ 332
Imax.SS
0.96
= 346
fabs~ ~0-0029 (°-29%)
As such, the adjusted fraction absorbed is 0.29%, approximately an 80 percent increase from the
measured 0.16% value.
Page 388 of 486
-------
Appendix F CONSUMER EXPOSURE ASSESSMENT
F.l Consumer Exposure
Consumer exposure was evaluated utilizing a modeling approach because emissions and chemical
specific personal monitoring data associated with consumer use of products containing 1-BP were
not identified during data gathering and literature searches performed as part of EPA's Systematic
Review process. A detailed discussion of the approaches taken to evaluate consumer inhalation
exposure is provided in Section 2.3.2.
F.2 Consumer Inhalation Exposure
Three models were used to evaluate consumer inhalation exposures, EPA's Consumer Exposure
Model (CEM), EPA's Multi-Chamber Concentration and Exposure Model (MCCEM), and EPA's
Indoor Environment Concentrations in Buildings with Conditioned and Unconditioned Zones
(IECCU) model. EPA varied three key parameters when modeling consumer inhalation exposure
to capture a range of potential exposure scenarios. The key parameters varied were duration of use
per event (minutes/use), amount of chemical in the product (weight fraction), and mass of product
used per event (gram(s)/use). These key parameters were varied because CEM is sensitive to all
three parameters and they are representative of expected consumer behavior patterns for product
use (based on survey data). Modeling was conducted for all possible combinations of the three
varied parameters. This results in a maximum of 27 different iterations for each consumer use as
summarized in TableApx F-l.
TableApx F-l. Example Structure of CEM Cases Modeled for Each consumer
Product/Article Use Scenario.
CEM Set
Scenario Characterization
(Duration-Weight Fraction-
Product Mass)
Duration of
Product Use
Per Event
(min/use)
[not scalable]
Weight Fraction of
Chemical in
Product (unitless)
[scalable]
Mass of Product Used
(g/use)
[scalable]
Set 1
(Low
Intensity
Use)
Case 1: Low-Low-Low
Low
Low
Low
Case 2: Low-Low-Mid
Mid
Case 3: Low-Low-High
High
Case 4: Low-Mid-Low
Mid
Low
Case 5: Low-Mid-Mid
Mid
Case 6: Low-Mid-High
High
Case 7: Low-High-Low
High
Low
Case 8: Low-High-Mid
Mid
Case 9: Low-High-High
High
Set 2
(Moderate
Intensity
Use)
Case 10: Mid-Low-Low
Mid
Low
Low
Case 11: Mid-Low-Mid
Mid
Case 12: Mid-Low-High
High
Case 13: Mid-Mid-Low
Mid
Low
Page 389 of 486
-------
Case 14: Mid-Mid-Mid
Mid
Case 15: Mid-Mid-High
High
Case 16: Mid-High-Low
High
Low
Case 17: Mid-High-Mid
Mid
Case 18: Mid-High-High
High
Set 3
(High
Intensity
Use)
Case 19: High-Low-Low
High
Low
Low
Case 20: High-Low-Mid
Mid
Case 21: High-Low-High
High
Case 22: High-Mid-Low
Mid
Low
Case 23: High-Mid-Mid
Mid
Case 24: High-Mid-High
High
Case 25: High-High-Low
High
Low
Case 26: High-High-Mid
Mid
Case 27: High-High-High
High
F.3 Consumer Dermal Exposure
Two models were used to evaluate consumer dermal exposures, the CEM (Fraction Absorbed)
model and the CEM (Permeability) model. A third dermal model from a paper published by Frasch
(Frasch and Bunge. 2015) was considered but not selected for use in this evaluation. A brief
comparison of these three dermal models through the calculation of acute dose rate (ADR) is
provided below. This is followed by comparison of results from all three models for all eight
conditions of use evaluated for dermal exposure for the adult age group. Finally, a brief discussion
on a sensitivity analysis of the three models is provided along with explanations related to why the
two CEM models were selected and utilized to evaluate dermal exposure for this risk evaluation.
F.3.1 Comparison of Three Dermal Model Methodologies to Calculate Acute Dose
Rate (ADR)
CEM (Permeability) Model: The CEM (Permeability) model estimates acute dose rates based
primarily on the permeability coefficient of the chemical of concern and duration of use. The CEM
(Permeability) model assumes a constant supply of product on the skin throughout the exposure
duration and does not consider evaporation from the skin. The CEM (Permeability) model
estimates the acute dose rate (ADR) using the following equation:
Equation Apx F-l. CEM Permeability Model, Acute Dose Rate
SA
Kp x Dac x Dil x p x ™ x FQac x WF x EDac x CF1
ADR = Tzr ^
ATac x CF2
The key inputs driving this calculation are the permeability coefficient (Kp), duration of use,
product density (p), and weight fraction (WF). The Kp is particularly important in this calculation
because its values can vary widely for a single chemical depending on the literature or estimation
Page 390 of 486
-------
source. The CEM (Permeability) model the permeability coefficient is estimated as a function of
the permeation coefficients of the lipid medium, protein fraction of the stratum corneum, and the
water epidermal layer utilizing the following equation:
EquationApx F-2. CEM Permeability Model, Permeability Coefficient KP
(f«p+fp j+(«y
CEM (Fraction Absorbed) Model. The CEM (Fraction Absorbed) model estimates dermal
exposure for products that are applied on the skin in a thin film and partially absorbed. This partial
absorption is modeled by an absorption fraction which accounts for the amount of substance that
penetrates across the absorption barriers of an organism. The CEM (Fraction Absorbed) model
requires an assumption that the entire mass of the chemical of concern within the thin film enters
the skin surface (stratum corneum) to correctly apply the absorption fraction. Utilizing this
assumption, the CEM (Fraction Absorbed) model estimates the (ADR) using the following
equation:
Equation Apx F-3. CEM Absorption Fraction Model, Acute Dose Rate
SA
AR X RW X FQ"c X FR"bs x Dil X WF X EDac X CFl
ADR = —
ATac
All terms listed in the above equation are singular inputs except AR, the amount retained on skin,
and FRabs, the absorption fraction (or fraction absorbed). The amount retained on skin (AR)
represents the amount of product remaining on the skin after use, and is in the units of grams of
product per square centimeter of skin area. Equation Apx F-4 shows the AR variable can be
calculated as a product of the film thickness of the liquid on the skin's surface and the density of
the product, subtracting any removal that may occur through washing or other removal methods.
Equation Apx F-4. CEM Absorption Fraction Model, Amount Retained on Skin
AR = FT x p x (1 - FracRemove)
The absorption fraction (FRabs) represents how much of the available material can be absorbed into
the skin and can be estimated through an exponential function defined primarily by D, the duration
of use, and/, the ratio of the evaporation rate from the stratum corneum surface to the dermal
absorption rate through the stratum corneum. The equation for FRabs, Equation Apx F-5, is a
simplification of the equation used by Frasch (Frasch and Bunge. 2015).
Equation Apx F-5. CEM Absorption Fraction Model, Fraction Absorbed
„ _ 3 + J [l - exp
abs 3(1+at)
Page 391 of 486
-------
The equation for/, EquationApx F-6, relies on chemical properties like molecular weight and
vapor pressure, making / values chemical-specific.
Equation Apx F-6. CEM Absorption Fraction Model, /
h X PVap X MW x CF1
X ~ Kpx Swx R XT
After simplifying the acute dose rate equation and substituting in for constants, the CEM
Absorption Fraction acute dose rate becomes a function of the product density, film thickness,
fraction absorbed, and weight fraction. Though the duration of use does impact the FRabs term, its
influence only extends to the limit of the FRabs equation. As the duration of use and % value
approach infinity the FRabs will plateau at 3.33E-01.
The relationship between duration and FRabs will be explained in greater detail in the sensitivity
analysis section and will highlight the relationship between CEM FRabs values and Frasch Fabs
values.
Frasch Model (Frasch andBunge. 2015) : The absorption fraction methodology presented by
Frasch (Frasch and Bunge. 2015) provides a dose calculation for a fully transient exposure. A fully
transient exposure is one in which dermal exposure occurs from an unlimited supply of chemical
against the skin for a finite duration. The chemical is then fully removed from the skin surface at
the end of the exposure with the assumption that no residue remains on the exposed section of skin,
although a portion of chemical remains within the skin surface (stratum corneum). This fully
transient exposure framework then considers a fraction of the chemical within the skin, not residue
at the surface, at the end of the exposure period (or duration of product use), can still enter the
systemic circulation. If the chemical has some volatility, a portion of the chemical within the skin
will evaporate before it has a chance to be absorbed by the body. The Frasch equation for
calculating the ADR is as follows:
Equation Apx F-7. Frasch, Acute Dose Rate
mT x CF x FQ x ED
ADR= wTTt
Similar to the CEM (Fraction Absorbed) model, all terms listed in the above equation are singular
inputs except mi, the total mass absorbed, which represents the mass of the chemical that has been
absorbed into the body at the end of the exposure time or duration of product use and the fraction
absorbed following the exposure time. The total mass absorbed is therefore calculated by the
following equation:
Equation Apx F-8. Frasch. Total Mass Absorbed hit
mr = mabs(t
exp ) Fabs™-0
The first term in the total mass calculation represents the mass absorbed at the end of the exposure
time or duration of product use. This mass term, mabs(texP), includes absorption throughout the use
of the product. The second mass term, mo, in the total mass calculation represents the mass of the
Page 392 of 486
-------
product left at the end of the exposure duration. This ending mass is then multiplied by the
absorption fraction, Fabs, to find the mass absorbed after the exposure duration or the duration of
product use has ended (the Frasch methodology uses Fabsto denote the fraction absorbed, as
opposed to FRabs used in the CEM (Fraction Absorbed) model). Each of the mass terms is given
per unit area within the stratum corneum and considers the permeability coefficient, exposure
duration, lag time, and the differential solution of the concentration distribution. A more in-depth
explanation of each mass term will be provided in the sensitivity analysis section.
EquationApx F-9. Frasch, Mass Absorbed at End of Exposure Time mabs(texP)
n2n2 t.
^absi^exp) kpCyt
lag
texp 12 Y> (-l)n j
1 7 > exp -
*lag 71 71 V
^exp
6 t,
lag,
Equation Apx F-10. Frasch, Mass at the End of Exposure Time mo
Wig kpCv^iag
00
8 V"1 1
n2 2-i (2n + 1):
71 = 0
¦exp
(2n + 1)27t2 t,
exp
6
llag,
The fraction absorbed, Fabs, is calculated based on the concentration distributions as well, using the
following equation:
Equation Apx F-ll. Frasch, Fraction Absorbed Fabs
3 +/
Fabs ~
mabsi™)
12 (zirexD
i+7l2Ln=i n2 exp
/—n27r2 texp\
V ^ tlag)
-I ^ V>00
1 jj-2 £->n=0
(2n + 1):
¦exp
—(2n + 1)27t2 t,
6
^exp \
^lag ).
m0
3(1+/)
This fraction absorbed equation can be simplified into the one used in the CEM (Fraction
Absorbed) model, described in the previous section.
F.3.2 Comparison of Estimated ADRs Across Three Dermal Models
The three dermal models described in Section F.3.1 were each run for all eight conditions of use
for which consumer dermal exposure was evaluated. The purpose was to allow a comparison
between the three results while recognizing each model is unique in its approach to estimating
dermal exposure and may not be directly comparable. Keeping these limitations in mind,
Table Apx F-2 shows the results from all three dermal models for each condition of use evaluated
for dermal exposure.
Table Apx F-2. Comparison of Adult Acute Dermal Exposure Estimates from Three Dermal
Models
Assessed Condition of Use
Scenario Description
Adult Acute Dermal Exposure (by method)
Page 393 of 486
-------
Average Daily Dose/Rate (mg/kg/day)
Permeability
Fraction Absorbed
Frasch
High intensity use
Aerosol spray degreaser/cleaner-general Moderate intensity use
Low intensity use
3.54E+00
2.35E-01
1.69E-02
1.11E-01
5.90E-02
1.27E-02
2.98E-01
3.73E-02
1.24E-02
High intensity use
Aerosol spray degreaser/cleaner-
, • Moderate intensity use
electronics
Low intensity use
3.68E-01
1.81E-02
3.13E-03
4.61E-02
3.42E-02
2.35E-02
2.98E-02
1.99E-03
5.00E-04
High intensity use
Spot cleaner and stain remover Moderate intensity use
Low intensity use
8.71E-01
9.13E-02
4.34E-03
1.09E-01
6.88E-02
3.27E-02
7.45E-02
1.24E-02
1.25E-03
High intensity use
Coin and scissors cleaner Moderate intensity use
Low intensity use
7.56E-02
3.78E-02
1.26E-02
9.49E-02
7.12E-02
4.75E-02
5.97E-03
3.99E-03
2.00E-03
High intensity use
Spray cleaner-general Moderate intensity use
Low intensity use
3.55E+00
4.44E-01
5.92E-02
1.11E-01
1.11E-01
1.11E-01
2.98E-01
3.73E-02
4.98E-03
High intensity use
Adhesive accelerant Moderate intensity use
Low intensity use
7.65E-01
5.42E-02
6.37E-03
4.80E-02
4.80E-02
4.80E-02
5.96E-02
4.23E-03
4.99E-04
High intensity use
Automobile AC flush Moderate intensity use
Low intensity use
3.96E+00
1.98E+00
6.60E-01
4.97E-01
4.97E-01
4.97E-01
3.79E-01
1.89E-01
6.32E-02
High intensity use
Mold cleaning and release products Moderate intensity use
Low intensity use
2.23E-01
1.49E-02
1.98E-03
4.27E-02
2.80E-02
1.49E-02
2.98E-02
1.99E-03
4.99E-04
Generally, the estimated exposure concentrations for 1-BP are highest utilizing the CEM
(Permeability) model for high intensity use scenarios under all but one condition of use (coin and
scissors cleaner). Additionally, estimates from the CEM (Permeability) model for those high
intensity use scenarios is approximately one order of magnitude higher than CEM (Fraction
absorbed) model estimates and Frasch model estimates.
Estimated exposure concentrations for 1-BP at moderate intensity uses are highest utilizing CEM
(Permeability) model for five of the eight conditions of use evaluated. The remaining three
conditions of use have higher estimated exposure concentrations utilizing the CEM (Fraction
Absorbed) model.
Estimated exposure concentrations for 1-BP at low intensity uses are higher utilizing the CEM
(Fraction Absorbed) model for all but one condition of use (aerosol spray degreaser/cleaner-
general). The majority of the estimates tend to be within an order of magnitude compared to the
CEM (Permeability) method.
Page 394 of 486
-------
The Frasch model estimates are consistently lower than the CEM (Permeability) model estimates.
They are also lower than the CEM (Fraction Absorbed) model estimates in all but three high
intensity use scenarios within the Aerosol spray degreaser/cleaner-general, spray cleaner-general,
and adhesive accelerant conditions of use. For these three specific scenarios the Frasch model is
higher than the CEM (Fraction Absorbed) model but still lower than the CEM (Permeability)
model.
It is possible that the Frasch model tends to be lower due to its consideration of lag time in both
mass components as well as the use of a Cv term, identified in equations Apx F-9 and Apx F-10,
which is based on solubility rather than density. Since density can be orders of magnitude higher
than solubility, adjusting the Cv for density could result in considerable increases within the mass
term utilized in the ADR equation. This may drive the Frasch model estimates closer to the CEM
(Permeability) model estimates but would require a change to the published Frasch model.
F.3.3 Sensitivity Analysis of Three Dermal Models
Selection of the models used to evaluate dermal exposure considered the sensitivity of the three
models as well as the representativeness of the model estimates to the expected consumer exposure
scenarios for each condition of use. The sensitivity and impacts of several parameters within the
three dermal models considered are discussed below followed by a broad consolidation of
considerations which led to EPA's selection of the CEM (Permeability) model and the CEM
(Fraction Absorbed) model to estimate dermal exposures for this evaluation.
F.3.3.1 Duration of Use
The duration of use for this evaluation was assumed equal to the exposure time for all three
models. The basic relationship between the duration of use or exposure time to the acute dose rate
is quite distinct for each of the three models. The CEM (Permeability) model and the Frasch model
maintain a strong positive correlation between duration of use and ADR, with ADR increasing by
the same factor of the duration of use. The exact slopes of these lines are influenced differently by
other factors, such as weight fraction, which will be discussed later. The CEM (Fraction Absorbed)
model maintains a logarithmic relationship between duration of use and ADR, hitting a horizontal
asymptote limit of 3.33E-01 after a certain duration (that duration varies by chemical). This limit
will be discussed in the next section as it relates to the fraction absorbed term.
F.3.3.2 Fraction Absorbed
The fraction absorbed is essentially the factor that determines what mass of chemical is absorbed
into the body. It is intended to be the mass absorbed from the stratum corneum as presented by
Frasch (Frasch and Bunge. 2015). but the CEM (Fraction Absorbed) model and Frasch model
calculate and utilize this factor differently. In terms of the equations within the two models
utilizing fraction absorbed, the CEM (Fraction Absorbed) model identifies this factor as FRabs
while Frasch identifies this factor as Fabs.
For both the CEM (Fraction Absorbed) model and the Frasch model, the fraction absorbed factor
relies on % (the ratio of evaporation rate to steady-state dermal permeation rate), the exposure time,
and certain physical-chemical properties (e.g., molecular weight, vapor pressure). As the % value
Page 395 of 486
-------
increases, at least 2h of the chemical in the skin will evaporate at the end of the exposure.
Therefore, for highly volatile chemicals with large % values (e.g., 1-BP) the fraction absorbed
factor will quickly reach a maximum (V3) with increasing duration (represented by taking the limit
at infinity of the absorption fraction equations). After a certain duration, the fraction that will
evaporate, and the fraction that will be absorbed remains constant.
The lag time (calculated based on the chemical molecular weight) used in the two fraction
absorbed equations influences how quickly the fraction absorbed limit of 3.33E-01 is reached.
Chemicals with shorter lag times will reach the limit of FRabs at shorter durations of use. For 1-BP,
the calculated lag time is about 0.77 with an estimated % value of about 4218. This results in the
FRabs for 1-BP reaching the limit of 3.33E-01 at an exposure time of about 90 minutes (based on an
estimated Kp of 0.0196). Linking this to the calculation of the ADR in the CEM (Fraction
Absorbed) model, while duration of use influences the fraction absorbed term, and the fraction
absorbed term influences the ADR, the influence of the fraction absorbed on the ADR calculation
peaks as the fraction absorbed approaches the 3.33E-01 limit. Therefore, for 1-BP, while the
fraction absorbed term increases quickly as exposure time increases, after about 90 minutes, the
exposure time has little influence on the fraction absorbed or the ADR.
Unlike the CEM (Fraction Absorbed) model, the Frasch model is not limited by the fraction
absorbed term in the same way. This is the case because the Frasch method considers both the
mass absorbed into the skin after the exposure time ends and the absorption during the use of the
product or chemical.
However, the weight fraction and amount retained on skin terms used in CEM ultimately control
the ADR value and will be discussed in the next sections.
F.3.3.3 Mass Terms
Ultimately, the ADRs for the three models are driven by how much product is available and
absorbed into the skin. However, all three models calculate those mass terms quite differently. To
help distinguish the three models apart, the mass terms were investigated primarily as they relate to
the exposure time (assumed to be the duration of product use obtained from survey data in this
evaluation).
The CEM (Permeability) model calculates the mass absorbed term within the ADR equation
(equation Apx_F-l) based on the permeability coefficient, dilution factor, duration of exposure,
density, surface area of skin, and weight fraction. The dilution factor is assumed to be 1 in all
modeling scenarios (no dilution). The product of these terms gives the mass of the chemical of
concern absorbed by the body from exposure to the modeled product(s). The CEM (Permeability)
model assumes an unlimited supply of the product is present against the skin for the entire duration
period and does not consider losses due to evaporation or rinsing.
The CEM (Fraction Absorbed) model calculates the mass available for absorption within the ADR
equation (equation Apx_F-3) utilizing the following terms: amount retained on skin (the
mathematical product of film thickness and product density), the surface area of skin, and weight
fraction. The product of these terms multiplied by the absorption fraction gives the total absorbed
mass. This assumes that the product or chemical is applied once to the skin's surface in a thin film
Page 396 of 486
-------
and then absorbed based on the absorption fraction. What this model doesn't consider is the mass
of the product or chemical that may enter the skin continuously during the use of the product or
chemical.
The Frasch (Frasch and Bunge. 2015) model calculates the total mass of the chemical of concern
taken into the body, for the ADR equation (Equation Apx F-7), in two parts: (1) mass taken in
during the duration of exposure and (2) mass absorbed into the body from the product that remains
within the skin (in the stratum corneum) after the duration of exposure. These mass values are
found through the solutions to differential functions based on permeation and diffusion
characteristics. The mass taken in during the period of use is calculated based on the assumptions
that the skin does not initially contain any of the chemical before the specified exposure duration,
the skin is exposed to a constant concentration for that specified exposure duration, and that the
chemical does not bind to the skin while the skin acts as a perfect sink at the bottom of the tissue.
This mass term creates the potential for overestimation of exposure based on the assumption that
the exposure is constant throughout the use of the product. The other mass term considers the
absorption of the chemical after the exposure duration ends. This absorption occurs from any
chemical remaining within the skin (in the stratum corneum) that does not evaporate.
Because neither the CEM (Permeability) model nor the CEM (Fraction Absorbed) model considers
the mass of chemical in the ADR equations, both models have the potential to overestimate the
dermal absorption by modeling a mass which is larger than the mass used in a scenario. Therefore,
when utilizing either of the CEM models for dermal exposure estimations, a mass check is
necessary outside of the CEM model to make sure the mass absorbed does not exceed the mass
used in a given scenario. Unlike the two CEM models, the Frasch model has built in mass checks
such that the mass calculated by the model is not larger than the mass being applied in a scenario.
F.3.3.4 Weight Fraction
Both the CEM (Permeability) model and the CEM (Fraction Absorbed) model calculate mass
values considering a weight fraction multiplier. This gives the weight fraction a potential to have
considerable influence over the final ADR. The Frasch model does not consider a weight fraction
in its calculations, although it is referenced in the mass checks mentioned above. As a result,
weight fraction does not change the calculated ADR in the Frasch model, although it can impact
the scale at which the Frasch estimates compare to the CEM ADR values.
The weight fraction term in both the CEM (Permeability) model and the CEM (Fraction Absorbed)
model influences the mass over time component of the models. A higher weight fraction results in
a higher mass term within the models. In contrast, the mass components of the Frasch model are
not affected by weight fraction and therefore do not increase with increased weight fractions.
The influence of weight fraction on the relationship between duration of use and acute dose rate
(ADR) is similar to that between duration of use and the modeled mass terms for the two CEM
models. As noted in Section F.3.3.1, the weight fraction influences the slope of the curves
associated with the duration of use and ADR. Although not the only factor, since both CEM
models are affected by weight fraction and the Frasch model is not, the relative ADR estimates
from the three models can vary considerably under scenarios with different weight fractions. At
Page 397 of 486
-------
lower weight fractions, the Frasch estimates are more likely to be greater than estimates from either
of the CEM model estimates. However, at higher weight fractions, the CEM (Permeability) model
estimates will begin to be greatest, in particular over increasingly high durations of use.
F.3.3.5 Permeability Coefficients
The permeability coefficient (Kp) is a term used in all three of the dermal models considered for
this evaluation. This value represents the rate of transfer of a compound across a membrane
(cm/hr). The Kp value is used directly in the ADR calculation within the CEM (Permeability)
model and therefore has a direct influence on the ADR estimates. The Kp value indirectly
influences the ADR estimates within the CEM (Fraction Absorbed) model through the fraction
absorbed term (via x)- The Kp value also indirectly influences the ADR calculation within the
Frasch model through the fraction absorbed term (via x), but also in its use within both mass term
calculations (therefore influencing total mass absorbed).
Experimental Kp values may be found in the literature or can be estimated utilizing various
methods. Experimental Kp values can be directly entered into both CEM dermal models or can be
estimated within CEM as described in the CEM Users Guide (U.S. EPA. 2019a) and associated
User Guide Appendices (U.S. EPA. 2019b). The Frasch model also provides a method to estimate
Kp in (Frasch and Bunge. 2015).
The sensitivity of the three models to changing Kp values on the ADR estimates shows the CEM
(Permeability) model has a very strong response to changing Kp values in relation to the slope of
the curve. Larger Kp values increase the slope of the curve showing the ADR estimates resulting in
a much more rapid increase in ADR estimates over a shorter duration of use. A similar influence of
changing Kp values can be seen with the Frasch model, although to a lesser degree than seen with
the CEM (Permeability) model. The CEM (Fraction Absorbed) model is only very slightly
influenced by changing Kp values.
F.3.3.6 Other Parameters
While the parameters discussed in previous sections have the potential to significantly impact ADR
estimates from the three models, other parameters can still influence the model outputs or provide
insight into differences between model outputs.
Product Density. Product density is a factor in both the CEM (Permeability) model and the CEM
(Fraction Absorbed) models but not within the Frasch model. Product density is directly utilized
within the CEM (Permeability) model ADR calculation and indirectly utilized within the CEM
(Fraction Absorbed) model ADR calculation (through amount retained on skin). While not directly
used within the Frasch model, it is utilized in the mass checks described previously.
Both of the CEM model ADR estimates change proportionately to changes in the product density,
while the Frasch ADR does not respond. While the general behavior and curve shapes for the ADR
do not appear to change much for either of the CEM models in response to product density, the
ADR estimates decrease with lower densities. Though the influence of product density does not
explain or describe much difference between the CEM (Permeability) model and the CEM
Page 398 of 486
-------
(Fraction Absorbed) model ADR estimates the absence of product density from the Frasch model
is a consideration when comparing the CEM model outputs to Frasch model outputs.
Film Thickness on Skin: Film thickness is only an input to the CEM (Fraction Absorbed) model
ADR calculations (as an input to the amount retained on skin term). Similar to the product density
influence, the ADR estimates from the CEM (Fraction Absorbed) model change proportionately to
changes in the film thickness. A larger film thickness results in a larger ADR estimate with the
CEM (Fraction Absorbed) model.
F.3.3.7 Selection of Dermal Models
Three dermal models were evaluated, outputs compared, and a sensitivity analysis conducted on all
three models to help identify fit-for-purpose models which would be representative of expected
consumer exposure scenarios for eight conditions of use involving 1-BP containing products. Two
general exposure scenarios were applied to select conditions of use.
1) Evaporation is inhibited/prohibited or full immersion of a body part occurs during product use.
2) Evaporation is uninhibited and full immersion of a body part does not occur during product use.
When applying the general constructs outlined above, both the CEM (Permeability) model and
Frasch model have a component which is applicable to conditions of use where evaporation is
inhibited/prohibited or full immersion of a body part occurs during use. However, only the CEM
(Permeability) model directly considers product density (rather than solubility) within components
of the ADR equation. Since most of the products utilized for these conditions of use are solvent
based (rather than aqueous), utilization of the CEM (Permeability) model along with a neat
permeability coefficient (Kp) is expected to provide a more representative ADR estimate for this
evaluation.
When applying the general constructs outlined above, both the CEM (Fraction Absorbed) model
and the Frasch model have a component which is applicable to conditions of use where
evaporation is uninhibited and full immersion of a body part does not occur during use. Similar to
the discussion above, the products utilized for these conditions of use are solvent based (rather than
aqueous) based. Since the CEM (Fraction Absorbed) model considers product density (indirectly
through the amount retained on skin), utilization of the CEM (Fraction Absorbed) model is
expected to provide a more representative ADR estimate for this evaluation. Further, while the
Frasch model has a fraction absorbed component, it also has the transient exposure with an
unlimited supply of product against the skin during the exposure period which may not be directly
applicable to the conditions of use where evaporation is assumed to be uninhibited for the entire
duration of product use.
Page 399 of 486
-------
Appendix G ECOSAR Modeling Outputs
The Ecological Structure Activity Relationships (ECOSAR) Class Program (v2.0) (EPA 2017) is a
computerized predictive system that estimates aquatic toxicity. The program estimates a chemical's
acute (short-term) toxicity and chronic (long-term or delayed) toxicity to aquatic organisms, such
as fish, aquatic invertebrates, and aquatic plants, by using computerized Structure Activity
Relationships (SARs). More information on the program can be found at:
https://www.epa.gov/tsca-screening-tools/ecological-structure-activitv-relationships-ecosar-
predictive-model
Created on Aug 29, 2019 3:31:41 PM
Organic Module Report
Results of Organic Module Evaluation
Name
CAS
SMILES
106945 Propane, 1-bromo-
BrCCC
Structure
CH3
Br
Details
Mol Wt
122.99
Selected LogKow
2.16
Selected Water Solubility (mg/L)
2450
Selected Melting Point (°C)
-110
Estimated LogKow
2.16
Estimated Water Solubility (mg/L)
2402.61
Measured LogKow
2.1
Measured Water Solubility (mg/L)
2450
Page 400 of 486
-------
Measured Melting Point (°C) -110
Neutral Organics
Organism
Duration
End Point
Concentration
(mg/L)
Max Log
Kow
Flags
Fish
96h
LC50
72.85
5
Daphnid
48h
LC50
41.97
5
Green Algae
96h
EC50
33.21
6.4
Fish
ChV
7.24
8
Daphnid
ChV
4.26
8
Green Algae
ChV
8.98
8
Fish (SW)
96h
LC50
91.79
5
Mysid
96h
LC50
61.29
5
Organism
Duration
End Point
Concentration
(mg/L)
Max Log Kow
Flags
Fish (SW)
ChV
10.97
8
Mysid (SW)
ChV
5.05
8
Earth womi
14d
LC50
205.91
6
Page 401 of 486
-------
Appendix H ESTIMATES OF SURFACE WATER
CONCENTRATION
SCENARIO 1. REPORTED RELEASES TO TRI
Estimating Surface Water Concentrations
Surface water concentrations were estimated for multiple scenarios using E-FAST which can be
used to estimate site-specific surface water concentrations based on estimated loadings of 1-
bromopropane into receiving water bodies. For TRI, the reported releases are based on monitoring,
emission factors, mass balance and/or other engineering calculations. These reported annual
loading amounts (lbs/year) were first converted to release inputs required by E-FAST (kg/day) by
converting from lbs to kgs and dividing by the number of release days for a given scenario.
E-FAST incorporates stream dilution at the point of release using stream flow distribution data
contained within the model. The stream flow data have not been updated recently and may differ
from current values obtained from NHD or USGS gages. Site-specific stream flow data 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 {i.e., Industrial POTW).
E-FAST 2014 can incorporate wastewater treatment removal efficiencies. Wastewater treatment
removal is assumed to be 0% for this exercise, as reported direct loadings/releases are assumed to
account for any pre-release treatment. Because the days of release and/or operation are not reported
in these sources, E-FAST is run assuming hypothetical release-day scenarios. Refer to the E-FAST
2014 Documentation Manual for equations used in the model to estimate surface water
concentrations (U.S. EPA. 2014b).
The modeled surface water concentrations presented below in Table Apx H-l are associated with
a low flow - 7Q10, which is an annual minimum seven-day average stream flow over a ten-year
recurrence interval. The 10th percentile 7Q10 stream flow is used to derive the presented surface
water concentrations. 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.
Modeled Surface Water Concentrations
It is assumed that these modeled surface water concentrations are higher than those that would be
present from non-point sources based on the conservative nature of the estimation approaches
including the following: surface water concentrations would be expected to decrease downstream
and this modeling analysis does not account for downstream transport and fate processes; non-zero
wastewater removal rates would be applied for any indirect releases that pass through a treatment
facility before release; and assuming a low-end number of release days (i.e., 1 day per year)
assumes the total annual loading estimate occurs over 1 day.
Page 402 of 486
-------
For 1-BP, there is one facility reporting non-zero water releases from the 2016 TRI reporting
period, the Flint Hills Resources facility. This facility, located in Corpus Christi, TX, has reported
1 lb of 1-BP released to the Neuces River with 100% from stormwater on an annual basis. They
also reported 4 lbs of 1-BP released to an unnamed water body with 83% from stormwater on an
annual basis. These are direct releases to water and thus are presumed to be untreated at a POTW.
A quick calculation of site-specific surface water concentration was performed using E-FAST
assuming that the total release occurs over 1 day, 20 days or 100 days. Two receiving waters were
used:
a. Neuces River - the NPDES permit for Corpus Christ City POTW TX0047082 was used as
a surrogate for this direct release. 0% removal was assumed since this is listed as a direct
release.
b. Unnamed Waterbody - the NPDES permit for the reporting facility was available in
EFAST with the receiving water body listed as the Corpus Christi Bay. Acute dilution
factors were used to estimate the surface water concentration, again with 0% removal.
The resulting estimated surface water concentrations presented below in TableApx H-l are based
on the reported releases and locations and are well below the acute and chronic concentrations of
concern even if the annual release amount occurs over 1 day. The maximum estimated surface
water concentration is 78 |ig/L for this scenario. The acute concentrations of concern are 13,460
|ig/L (96-hour fish LC50) and 3640 |ig/L (algae EC50) and the chronic concentrations of concern
are 673 |ig/L (fish chronic value) and 470 |ig/L (daphnia ChV).
Table Apx H-l. Estimated Surface Concentrations from Water Releases Reported to TRI
SCENARIO 1: REPORTED RELEASES TO TRI
Acute COC = 13460 |ig/L (96-hour fish LCso) and 3640 |ig/L (algae ECso)
Chronic COC = 673 |ig/L (fish chronic value) and 470 |ig/L (daphnia ChV)
From TRI reporting: 1 reporting facility: Flint Hills Resources Corpus Christi LLC - West Plant
1 lb to Neuces River (100% from stormwater);
4 lbs to 'unnamed waterbody' (83% from stormwater)
Wastewater Treatment Removal= 0%; direct release
(Note: NPDES for Corpus Christi City POTW used as surrogate for Neuces River. Flint Hills Resources facility modeled
directly)
Neuces River (Corpus Christi City -
TX0047082)
Flint Hills Resources - Corpus Christi Bay,
(TX0006289)
7Q10 SWC (ig/L
SWC* (ig/L
Annual Release
Amount lb (kg)
1 day/yr
20 days/yr
100 days/yr
1 day/yr
20 days/yr
100 days/yr
1 (0.45)
7.86
0.39
0.08
19.4
0.97
0.19
4 (1.81)
31.60
1.58
0.31
77.90
3.90
0.77
* Acute dilution factor for bay
Page 403 of 486
-------
Page 404 of 486
-------
Appendix I TOXICOKINETICS
The studies summarized in this section were identified for consideration in the human health
hazard assessment, as described in Section 3.2.3.
Empirical evidence from rodent toxicity studies and from occupational exposure studies indicate
that 1-BP is absorbed by both inhalation and dermal routes. Additional evidence of the systemic
uptake of 1-BP via the oral route has been reported (Lee et al.. 2007). Absorption is rapid by all
routes, and a significant portion of the absorbed dose (39% to 48% in mice and 40% to 70% in
rats) is eliminated in exhaled breath as unspecified volatile organic compounds (Garner et al..
2006; Jones and Walsh. 1979). Garner and Yu (2014) provided supplemental evidence on the
toxicokinetics of BP in rodents. Rodents exposed to 1-BP via intravenous injection or inhalation
exhibited rapid systemic clearance and elimination that decreased as the dose increased. Previous
studies showed that the remaining absorbed dose is eliminated, unchanged, in urine (humans) or as
metabolites in the urine and exhaled breath of all species studied (Garner et al.. 2006; Kawai et al..
2001). Available toxicokinetic data indicate that glutathione (GSH) conjugation and oxidation via
cytochrome P450 (CYP450) significantly contribute to the metabolism of 1-BP (Garner and Yu.
2014; Garner et al.. 2006).
1,1 Absorption
The detection of carbon-containing metabolites and elevated bromide ion concentrations in urine
samples of workers exposed to 1-BP by inhalation and dermal contact provides qualitative
evidence that 1-BP is absorbed by the respiratory tract and the skin in humans (Hanlev et al.. 2010.
2009; Valentine et al.. 2007; Hanlev et al.. 2006b). In addition, reports of neurological and other
effects in occupationally exposed subjects provide indirect evidence of absorption of 1-BP
(Samukawa et al.. 2012; CDC. 2008; Maiersik et al.. 2007; Raymond and Ford. 2007; NIOSH.
2003a; Ichihara et al.. 2002; Sclar. 1999).
Dermal absorption characteristics estimated in human epidermal membranes mounted on static
diffusion cells included steady-state fluxes averaging 625-960 |ig cm"2 hour"1 with pure 1-BP and
441-722 |ig cm"2 hour"1 with a commercial dry cleaning solvent, an average dermal penetration of
about 2% from an applied dose of 13.5 mg/cm2 under non-occluded conditions, and a dermal
permeability coefficient for 1-BP in water of 0.257 cm/hour (Frasch et al.. 2011).
Animal studies provide qualitative evidence of absorption by the gastrointestinal and respiratory
tracts (Garner et al.. 2006; Jones and Walsh. 1979). 13C-labeled metabolites were detected in urine
collected from rats and mice exposed by inhalation to 800 ppm [1,2,3-13C]-1-BP for 6 hours
(Garner et al.. 2006). A number of mercapturic acid derivative metabolites were detected in pooled
urine samples collected from rats given oral doses of 200 mg 1-BP/kg/day in arachis oil for five
days (Jones and Walsh. 1979).
No other human or animal studies were located that determined the rate or extent of 1-BP
absorption following inhalation, oral, or dermal exposure.
Page 405 of 486
-------
1,2 Distribution
Metabolic disposition studies in rats and mice given single intravenous injections of [1,2,3-13C]-1-
BP indicate that 1-BP is not expected to accumulate in tissues (Garner et al.. 2006). Following
intravenous injection of [1-14C]-1-BP at nominal doses of 5, 20, or 100 mg/kg, radioactivity
remaining in the carcass 48 hours after dose administration accounted for about 6, 6, and 2% of the
administered dose in rats, and 4, 2, and 4% in mice (Garner et al.. 2006). In these studies, most of
the administered radioactivity was exhaled (as the parent material or CO2) or excreted as
metabolites in urine.
1,3 Metabolism
The metabolism of 1-BP in mammals involves: (1) conjugation, principally with glutathione,
leading to the release of bromide ions and formation of mercapturic acid derivatives and
(2) cytochrome P-450 mediated oxidation leading to formation of metabolites with hydroxyl,
carbonyl, and sulfoxide groups, as well as CO2. These concepts are based on studies of urinary
metabolites in workers exposed to 1-BP (Hanlev et al.. 2010. 2009; Valentine et al.. 2007; Hanlev
et al.. 2006b). in vivo metabolic disposition studies in rats and mice (Garner et al.. 2007; Garner et
al.. 2006; Ishidao et al.. 2002; Jones and Walsh. 1979; Barnslev et al.. 1966). and in vitro
metabolism studies with rat liver preparations (Kaneko et al.. 1997; Tachizawa et al.. 1982; Jones
and Walsh. 1979).
N-Acetyl-S-propylcysteine has been identified in urine samples from workers in a 1-BP
manufacturing plant (Valentine et al.. 2007). in foam fabricating plants using spray adhesives
containing 1-BP (Hanlev et al.. 2010. 2009; Hanlev et al.. 2006b). and in degreasing operations in
plants using 1-BP as a cleaning solvent in the manufacture of aerospace components, hydraulic
equipment, optical glass, and printed electronic circuit assemblies (Hanlev et al.. 2009). Other
urinary metabolites identified in 1-BP workers are the bromide ion (Hanlev et al.. 2010) and three
oxygenated metabolites present at lower urinary concentrations than N-acetyl-S-propylcysteine: N-
acetyl-S-propylcysteine-S-oxide (also known as N-acetyl-3-(propylsulfinyl) alanine), N-acetyl-
S-(2-carboxyethyl) cysteine, and N-acetyl-S-(3-hydroxy-propyl) cysteine (Cheever et al.. 2009;
Hanlev et al.. 2009). The correlations between time weighted average workplace air concentrations
of 1-BP and urinary levels of bromide and N-acetyl-S-propylcysteine (Hanlev et al.. 2010. 2009;
Valentine et al.. 2007; Hanlev et al.. 2006b) support the hypothesis that conjugation with
glutathione is an important pathway in humans (see Figure 3-3). The detection of oxygenated
metabolites in urine samples indicates that oxidation pathways also exist in humans (see Figure 3-3
for structures of identified oxygenated metabolites).
Results from metabolic disposition studies in rats and mice illustrate that the metabolism of 1-BP
in mammals is complex, involving initial competing conjugation or oxidation steps, followed by
subsequent conjugation, oxidation, or rearrangement steps. Figure 3-3 presents proposed metabolic
pathways based on results from studies of F-344 rats and B6C3F1 mice exposed to [1-14C]-1-BP
by intravenous injection or [1,2,3-13C]-1-BP by inhalation or intravenous injection (Garner et al..
2006).
Page 406 of 486
-------
The metabolic scheme shows an oxidation path to CO2 formation which involves cytochrome P450
(CYP) oxidation steps to l-bromo-2-propanol and bromoacetone. This path is proposed based on
several findings:
1. Following intravenous injection of 14C-1-BP at nominal doses of 5, 20, or 100 mg/kg,
radioactivity in CO2 exhaled within 48 hours accounted for approximately 28, 31, and 10%
of the administered dose in rats, and 22, 26, and 19% in mice (Garner et al.. 2006). (These
data also indicate that oxidative metabolism of 1-BP in rats is more dependent on dose than
oxidative metabolism in mice; the decrease in percentage dose exhaled as CO2 at the
highest dose is greater in rats than mice.)
2. Pretreatment of rats with 1-aminobenzotriazole (ABT) before administration of a single
intravenous dose of -20 mg/kg 14C-1-BP or inhalation exposure to 800 ppm 13C-1-BP for
6 hours caused decreased exhalation of radioactivity as CO2 and decreased formation of
oxidative urinary metabolites (Garner et al.. 2006). ABT is an inhibitor of a number of CYP
enzymes (Emoto et al.. 2003).
3. Urinary metabolites derived from l-bromo-2-propanol accounted for over half of all
carbon-containing urinary metabolites identified in rats and mice exposed by inhalation or
intravenous injection of 13C-1-BP, and no l-bromo-2-propanol-derived metabolites were
found in urine of ABT-pretreated rats exposed to 13C-1-BP (Garner et al.. 2006). 1-Bromo-
2-propanol and bromoacetone themselves were not detected in urine of 1-BP-exposed
rodents.
Glutathione
^HN-Acetyl
HC COOH
\
XH,
1-Bromopropane
Br
H2C>
CH,
CH,
N-Acetyl-S-propylcysteine
FigureApx 1-1. Formation of N-Acetyl-S-Propylcysteine from 1-Bromopropane Via
Conjugation with Reduced Glutathione (GSH)
Page 407 of 486
-------
HN-Acetyl
HN-Acetyl
HC COOH
\
-CH0
o:
\
CH0
HC COOH
\
^CH0
CH0
H2C
\
ch3
N-Acetyl-S-propylcysteine-S-oxide
[also known as
N-acetyl-3-(propylsulfinyl)alanine]
h2cs
C OH
h2
N-Acetyl-S-(3-hydroxypropyl)cysteine
^HN-Acetyl
HC COOH
\
-CH0
\
CH0
h2cx
COOH
N-Acetyl-S-(2-carboxyethyl)cysteine
FigureApx 1-2. Mercapturic Acid Metabolites with a Sulfoxide Group or a Hydroxyl or
Carbonyl Group on the Propyl Residue Identified in Urine Samples of
1-Bromopropane-Exposed Workers
Sources: (Cheever et al.. 2009: Hanlev et al.. 2009)
Results from metabolic disposition studies indicate that 1-BP is eliminated from the body by
exhalation of the parent material and metabolically derived CO2 and by urinary excretion of
metabolites (Garner et al.. 2006; Jones and Walsh. 1979). Following intraperitoneal injection of
200 mg/kg of [1-14C]-1-BP in rats, about 60 and 1.4% of the administered dose was recovered as
the parent material and CO2 respectively, in air expired within 6 hours; about 15% of the
administered dose was recovered in urine collected over a 48- hour period (Jones and Walsh.
1979). Following intravenous injection of [1-14C]-1-BP at nominal doses of 5, 20, or 100 mg/kg,
the radioactivity in CO2 exhaled within 48 hours accounted for approximately 28, 31, and 10% of
the administered dose in rats, and 22, 26, and 19% in mice (Garner et al.. 2006). Radioactivity in
the exhaled parent material accounted for about 25, 32, and 71% of the administered dose in rats,
and 45, 39, and 48% in mice (Garner et al.. 2006). Radioactivity in urine collected for 48 hours
accounted for about 17, 19, and 13% of the administered dose in rats, and 23, 19, and 14% in mice
(Garner et al.. 2006). Radioactivity in feces accounted for <4% of administered doses, regardless of
dose level, in both species (Garner et al.. 2006).
Page 408 of 486
-------
Animal studies also show rapid elimination of 1-BP from the body (Garner and Yu. 2014; Garner
et al.. 2006; Ishidao et al.. 2002). Following intravenous injection of [1-14C]-1-BP at nominal doses
of 5, 20, or 100 mg/kg, radioactivity remaining in the carcass 48 hours after dose administration
accounted for about 6, 6, and 2% of the administered dose in rats, and 4, 2, and 4% in mice (Garner
et al.. 2006). (Garner et al.. 2006) proposed that radioactivity remaining in the carcass could
represent covalently bound residues from interactions with reactive metabolites or incorporation of
14C into cellular macromolecules. Following intravenous injection of 5 or 20 mg 1-BP/kg doses
into rats, the mean half-life for 1-BP elimination from blood was 0.39 or 0.85 hours, respectively
(Garner and Yu. 2014). In gas uptake studies with male and female rats, 1-BP elimination was
rapid, with a decrease in the elimination half-life observed with increasing air concentrations of 1-
BP (Garner and Yu. 2014). Pretreatment of female rats with ABT, an inhibitor of CYP metabolism
(intraperitoneal injection of 50 mg 1-BP/kg 4 hours prior to gas uptake measurements) or
buthionine sulfoxime, an inhibitor of glutathione synthesis (1,000 mg 1-BP/kg/day orally for
3 days before gas uptake), resulted in longer elimination half-times: 9.6 hours with ABT and 4.1
hours with D,L-buthionine(S,R)-sulfoximine (BSO), as compared with 2.0 hours in females not
pretreated with ABT or BSO prior to 1-BP exposure at 800 ppm in the gas uptake chamber (Garner
and Yu. 2014). These results suggest that oxidative metabolism and glutathione conjugation play
an important role in the elimination of 1-BP. Blood levels decreased rapidly (to detection limits) <
1 hour after the cessation of exposure in Wistar rats exposed to 700 or 1,500 ppm 1-BP 6 hours/day
for > 3 weeks (Ishidao et al.. 2002). Clearance of bromide ions from blood and urine showed
slower elimination kinetics; the elimination half-life for bromide was 4.7-15 days in blood and 5.0-
7.5 days in urine (Ishidao et al.. 2002).
Based on urinary metabolites identified with nuclear magnetic resonance spectroscopy, liquid
chromatography-tandem mass spectrometry, and high-performance liquid chromatography (Garner
et al.. 2006). the scheme in Figure 3-3 also shows an initial conjugation of 1-BP with glutathione
leading to N-acetyl-S-propylcysteine, an oxidation step from l-bromo-2-propanol to alpha-
bromohydrin, a glucuronic acid conjugation step from l-bromo-2-propanol to 1-bromo-
2-hydroxypropane-O-glucuronide, and glutathione conjugation of l-bromo-2-propanol and
bromoacetone followed by oxidation steps leading to metabolites with sulfoxide groups (e.g., N-
acetyl-3-[(2-hydroxypropyl)sulfinyl] alanine). The steps involving oxidation of sulfur in the
glutathione conjugate derivatives were proposed to be catalyzed by CYP oxygenases or flavin-
containing monooxygenases (FMO) as suggested by Krause et al. (2002).
Catalysis of the oxidation steps by a number of CYP enzymes is supported by results from
metabolic disposition studies in wild-type and Cyp2el-/- knock-out mice (F1 hybrids of 129/Sv
and C57BL/6N strains) exposed by inhalation to 800 ppm 13C-1-BP for 6 hours (Garner et al..
2007). Three major metabolites were identified in urine collected from wild-type mice during
exposure: N-acetyl-S-(2-hydroxypropyl) cysteine (34 |imoles in collected urine), 1-bromo-
hydroxypropane-(9-glucuronide (5 |imoles), and N-acetyl-S-propylcysteine (8 |imoles). In Cyp2el-
/- mice, the amounts of these metabolites in collected urine were changed to 21, 2, and 24 |imoles,
respectively. The ratio of 2-hydroxylated metabolites to N-acetyl-S-propylcysteine was
approximately 5:1 in wild-type and 1:1 Cyp2el-/~ mice. The results indicate that the elimination of
CYP2E1 increased the relative importance of the glutathione conjugation pathway, but did not
Page 409 of 486
-------
eliminate the formation of oxygenated metabolites, suggesting the involvement of other CYP
enzymes, in addition to CYP2E1, in oxidation steps illustrated in Figure 3-5.
Evidence for the initial conjugation of 1-BP with glutathione leading to the formation of N-acetyl-
S-propylcysteine comes from a number of studies in rats and mice (Garner et al.. 2007; Garner et
al.. 2006; Khan and O'Brien. 1991; Jones and Walsh. 1979).
1. N-Acetyl-S-propylcysteine was detected in the urine of wild-type and Cyp2el-/~ mice
exposed to 800 ppm 1-BP for 6 hours, at molar ratios to hydroxylated metabolites of 5:1
and 1:1 (Garner et al.. 2007).
2. N-Acetyl-S-propylcysteine and N-acetyl-3-(propylsulfinyl) alanine (i.e., N-acetyl-
S-propylcysteine-S-oxide) accounted for approximately 39 and 5% of excreted urinary
metabolites, respectively, in urine collected for 24 hours after inhalation exposure of rats to
800 ppm 1-BP for 6 hours (Garner et al.. 2006).
3. N-Acetyl-S-propylcysteine was a relatively minor urinary metabolite in rats given single 5-
mg 1-BP/kg intravenous doses, but accounted for >80% of urinary metabolites following
administration of 100 mg 1-BP/kg (Garner et al.. 2006).
4. N-Acetyl-S-propylcysteine and N-acetyl-S-propylcysteine-S-oxide were among the six
mercapturic acid derivatives identified in urine from rats given 200 mg 1-BP/kg by gavage
(in arachis oil) for 5 days (Jones and Walsh. 1979). The structures of the other four
mercapturic acid derivatives identified were consistent with glutathione conjugation of
oxygenated metabolites of 1-BP, rather than 1-BP itself. These included N-acetyl-S-(2-
hydroxypropyl) cysteine, N-acetyl-S-(3-hydroxypropyl) cysteine, and N-acetyl-S-(2-
carboxyethyl) cysteine (Jones and Walsh. 1979). The techniques used in this study did not
determine the relative amounts of the urinary mercapturic acid derivatives.
5. Isolated hepatocytes incubated for 60 minutes with 1-BP showed a decrease in glutathione
content (from 58.4 to 40.8 nmol/106 cells), consistent with the importance of glutathione
conjugation in metabolic disposition of 1-BP in mammals (Khan and O'Brien. 1991).
Other studies have identified other metabolites, not included in Figure 3-3, in urine from rats and
mice exposed to 1-BP (Ishidao et al.. 2002; Jones and Walsh. 1979) and in in vitro systems
(Kaneko et al.. 1997; Tachizawa et al.. 1982; Jones and Walsh. 1979). (Jones and Walsh. 1979)
reported detecting metabolites in urine from rats orally exposed to 1-BP that are consistent with the
initial oxidation of the 3-C of 1-BP: N-acetyl-S-(3-hydroxypropyl) cysteine, 3-bromopropionic
acid, and N-acetyl-S-(2-carboxyethyl) cysteine. (Garner et al.. 2006) were not able to detect these
Page 410 of 486
-------
metabolites in urine following administration of single intravenous doses up to 100 mg 1-BP/kg in
rats or exposure to 800 ppm for 6 hours in rats or mice. (Garner et al.. 2006) proposed that the
apparent discrepancy may have been due to an amplification of minor metabolites from the
pooling, concentration, and acid hydrolysis processes used in the earlier study. Glycidol (1,2-
epoxy-3-propanol) was detected in urine of Wistar rats exposed by inhalation 6 hours/day to 700
ppm for 3 or 4 weeks or 1,500 ppm for 4 or 12 weeks; but no determination of the amount of this
compound was made, and the report did not mention the detection of any other carbon-containing
metabolites (Ishidao et al.. 2002). (Kaneko et al.. 1997) monitored the formation of n-propanol
during incubation of rat liver microsomes with 1-BP. 3-Bromopropanol and 3-bromopropionic acid
were detected when 1-BP was incubated in an in vitro oxidizing system, but 1-BP metabolism with
rat liver homogenates was not examined due to the water solubility of 1-BP (Jones and Walsh.
1979). Propene, 1,2-epoxypropane, 1,2-propanediol, and propionic acid were detected when liver
microsomes from phenobarbital-treated rats were incubated with 1-BP, and the addition of
glutathione to the reaction mixture led to formation of S-(l' propyl)glutathione and S-(2' hydroxyl-
1' propyl) glutathione (Tachizawa et al.. 1982). (Garner et al.. 2006) reported that propene,
propylene oxide, propanediol, and propionic acid were not detected in liver homogenate
incubations with 1-BP; they suggested that the use of phenobarbital as a CYP inducer may have
resulted (in the (Tachizawa et al.. 1982) studies) in the formation of metabolites not generated by
constitutive CYP enzymes.
1-BP may be converted to either of two epoxide metabolites (see section 0-5-7), glycidol (which
was found in the urine of 1-BP-exposed rats, see above) and propylene oxide. Metabolic pathways
by which propylene oxide may be generated from 1-BP are shown in Jones and Walsh (Jones and
Walsh. 1979). NTP (2013b). and IARC (2018) and a pathway by which glycidol may be generated
from 1-BP is shown in IARC (2018).
1,4 Elimination
Results from animal metabolic disposition studies indicate that 1-BP is eliminated from the body
by exhalation of the parent material and metabolically derived CO2 and by urinary excretion of
metabolites (Garner et al.. 2006; Jones and Walsh. 1979). Following single intraperitoneal
injections of 200 mg/kg doses of [1 14C]-1-BP in rats, about 60 and 1.4% of the administered dose
was in parent material and CO2 in air expired within 6 hours, respectively, and about 15% of the
administered dose was in urine collected for 48 hours (Jones and Walsh. 1979). Following
intravenous injection of [1 14C] 1 bromopropane at nominal doses of 5, 20, or 100 mg/kg,
radioactivity in CO2 exhaled in 48 hours accounted for about 28, 31, and 10% of the administered
dose in rats, and 22, 26, and 19% in mice (Garner et al.. 2006). Radioactivity in exhaled parent
material accounted for about 25, 32, and 71% of the administered dose in rats, and 45, 39, and 48%
in mice (Garner et al.. 2006). Radioactivity in urine collected for 48 hours accounted for about 17,
19, and 13% of the administered dose in rats, and 23, 19, and 14% in mice (Garner et al.. 2006).
Radioactivity in feces accounted for <4% of administered doses, regardless of dose level, in both
species (Garner et al.. 2006).
Page 411 of 486
-------
Animal studies also show that the elimination of 1-BP from the body is rapid and accumulation in
the body is not expected (Garner and Yu. 2014; Garner et al.. 2006; Ishidao et al.. 2002).
Following intravenous injection of [1-14C]-1-BP at nominal doses of 5, 20, or 100 mg/kg,
radioactivity remaining in the carcass 48 hours after dose administration accounted for about 6, 6,
and 2% of the administered dose in rats, and 4, 2, and 4% in mice (Garner et al.. 2006). (Garner et
al.. 2006) proposed that radioactivity remaining in the carcass could represent covalently bound
residues from reactive metabolites or incorporation of 14C into cellular macromolecules from
intermediate metabolic pathways. Following intravenous injection of 5 or 20 mg 1-BP/kg doses
into rats, the mean half-times of elimination of 1-BP from the blood were 0.39 and 0.85 hours,
respectively (Garner and Yu. 2014). In gas uptake studies with male and female rats, calculated
half-times of elimination for 1-BP were rapid and decreased with increasing air concentrations of
1-BP (Garner and Yu. 2014). Terminal elimination half-times were 0.5, 0.6, 1.1, and 2.4 hours for
males, and 1.0, 1.0, 2.0, and 6.1 hours for females, exposed to initial air concentrations of 70, 240,
800, and 2,700 ppm, respectively. Pretreatment of female rats with ABT to inhibit CYP
metabolism (intraperitoneal injection of 50 mg 1-BP/kg 4 hours prior to gas uptake measurements)
or buthionine sulfoxime, an inhibitor of glutathione synthesis (1,000 mg 1-BP/kg/day orally for 3
days before gas uptake), resulted in longer elimination half-times: 9.6 hours with ABT and 4.1
hours with D,L-butionine(S,R)-sulfoximine (BSO), compared with 2.0 hours in untreated females
at 800 ppm 1 bromopropane in the gas uptake chamber (Garner and Yu. 2014). The results with the
inhibitors show that both CYP mediated oxidative metabolism and glutathione conjugation play
important roles in the elimination of 1-BP. Levels of 1-BP in blood decreased rapidly to detection
limits within 0.7 hours after exposure stopped in Wistar rats exposed to 700 or 1,500 ppm 1-BP 6
hours/day for >3 weeks (Ishidao et al.. 2002). Clearance of the bromide ion from blood and urine,
however, showed slower elimination kinetics: elimination half-times for bromide were 4.7-
15.0 days in blood and 5.0-7.5 days in urine (Ishidao et al.. 2002).
Page 412 of 486
-------
Appendix J ANIMAL AND HUMAN TOXICITY STUDIES
CONSIDERED FOR USE IN RISK ASSESSMENT
The 1-BP hazard information subjected to data quality evaluation consisted primarily of studies
designed to examine the effects of repeated inhalation exposure (e.g., liver and kidney toxicity) and
specialized repeated-dose studies of reproductive and developmental toxicity, neurotoxicity and
carcinogenesis. Most of the available laboratory animal studies were considered useful for
characterizing the potential human health hazards of 1-BP exposure; however, limitations were
noted in some studies. This hazard information is summarized in the evidence tables shown in
Table Apx J-2. Additional information regarding the data evaluation results for individual studies
can be found in the Draft Risk Evaluation for 1-Bromopropane (1-BP), Systematic Review
Supplemental File: Data Quality Evaluation of Human Health Hazard Studies. EPA-HQ-OPPT-
2019-0235 (EPA. 2019o). Any study evaluation concerns thought to have influenced the reliability
or interpretation of a specific hazard endpoint are discussed in the synthesis of evidence for a given
hazard (See section 3.2.5). All endpoints considered for dose-response analysis were obtained from
toxicity studies that scored high during data evaluation.
J,1 Reproductive Toxicity
A two-generation reproduction study in rats reported adverse effects on male and female
reproductive parameters (WTL Research. 2001). The majority of these effects exhibited a dose-
response beginning at 250 ppm, with statistical significance observed at 500 ppm. The Fo
generation showed significant dose-related decreases in male and female fertility indices at
500 ppm (fertility was 52% and 0% at 500 and 750 ppm, respectively). A significant increase in
the number of females that displayed evidence of mating without delivery was also observed at 500
(10 of 25, 40%) and 750 ppm (17 of 25, 68%) in the Fo generation. In the Fi generation, the
number of females that displayed evidence of mating without delivery was greater than controls,
but not statistically significant at 500 ppm (8 of 25, 32% versus 3/25, 12% in treated and control
dams, respectively). The number of males in the Fo generation that did not sire a litter numbered 2,
0, 3, 12 and 25 (8, 0, 12, 48 and 100%) in the control, 100, 250, 500 and 750 ppm groups
respectively. In addition, two females treated at 500 ppm showed evidence of mating, and were
gravid, but did not deliver litters. The number of implantation sites, the actual number of litters
produced, and live litter size were significantly reduced at 500 ppm in the Fo and Fi generations.
Significant changes in female reproductive parameters included a decrease in absolute and relative
ovary weights at 750 ppm in the Fo generation and an increase in estrous cycle length in Fo and Fi
females (500 ppm). Estrous cycling was not observed in two Fo females in the 500 ppm group,
three Fo females in the 750 ppm group, three Fi females in the 250 ppm group, and four Fi females
in the 500 ppm group. This finding is supported by an inhalation study which showed significant
treatment-related effects on estrous cycling in female rats and mice following three months of 1-BP
inhalation exposure at > 250 ppm (NTP. 2011a).
The toxicological significance of these findings is underscored by related findings at comparable
doses in Fo and Fi generations:
Page 413 of 486
-------
• Decreased fertility (significant in 500 and 750 ppm groups). Because both males and
females were treated, the observed decreases in fertility could be due in part, to dose-related
impairment of male reproductive function.
• An increase in the number of primordial follicles at the highest dose evaluated (750 ppm in
Fo and 500 ppm in Fi) and a decrease in the number of corpora lutea in Fo females at
> 500 ppm (significant at 750 ppm; endpoint was not measured at 100 or 250 ppm).
• No difference in the numbers of corpora lutea was observed in Fi females treated at
500 ppm as compared to control (no other doses were evaluated for this endpoint).
• A significantly decreased number of implantation sites in Fo and Fi females at > 500 ppm
(no implantations observed at 750 ppm).
• Decreased live litter size (significant at 500 ppm in Fo and Fi treatment groups).
Statistically significant changes in male reproductive and spermatogenic endpoints included:
• Decreased sperm motility and morphologically normal sperm in the Fo (> 500 ppm) and Fi
generations (500 ppm)
• Reduced absolute weight of the left and right cauda epididymides at > 500 ppm in Fo/Fi
• Decreased absolute prostate weight in Fo (> 250 ppm) and Fi males (500 ppm)
• Decreased seminal vesicle weight in Fo (750 ppm) and Fi males (250 ppm)
• Decreased mean epididymal sperm numbers in Fo males at 750 ppm
These findings positively correlate with the negative effects on fertility observed at 500 ppm, and
the complete lack of fertility observed in Fo mating pairs treated at 750 ppm.
(Zona et al.. 2016) investigated the potential effects of 1-aminobenzotriazole (1-ABT), a general
inhibitor of cytochrome P450s, on the induction of toxicity to the reproductive system of male
mice that were exposed by inhalation to vapors of 1-bromopropane (1-BP). Groups of six 10-week-
old male C57BL/6J mice were exposed whole-body to 1-BP for 8 hours/day, 7 days/week for 4
weeks at vapor concentrations of 0, 50, or 250 ppm with twice-daily s.c. injections of saline and at
0, 50, 250, or 1200 ppm with twice-daily s.c. injections of 50 mg 1-ABT/kg in saline. Timing of 1-
ABT/saline injections was not indicated. The only treatment-related effect on body weight at the
end of exposure was significantly lower mean body weight in mice exposed to 1200 ppm 1-BP/l-
ABT, compared with the 1-ABT-treated control. Weights of prostate plus seminal vesicle were
significantly decreased at 250 ppm 1-BP without 1-ABT treatment and at 250 ppm and 1200 ppm
1-BP with 1-ABT treatment. No other organ weights were affected in mice that were exposed to 1-
BP in the absence of 1-ABT treatment. However, in mice treated with 1-ABT, spleen weights were
significantly decreased at 50, 250, and 1200 ppm 1-BP and testes and epididymide weights were
significantly decreased at 1200 ppm 1-BP. Epididymal sperm count and percent mobile sperm
were significantly decreased at 250 ppm 1-BP in the absence of 1-ABT treatment but were not
decreased at 250 ppm 1-BP in the 1-ABT-treated mice. In mice exposed to 1200 ppm 1-BP and
treated with 1-ABT, epididymal sperm count, percent mobile sperm, and the number of round
spermatids per seminiferous tubule were significantly decreased, and percent morphologically
Page 414 of 486
-------
abnormal epididymal sperm was significantly increased. The number of retained elongated
spermatids per seminiferous tubule was significantly increased at 50 and 250 ppm 1-BP without 1-
ABT treatment, but only at 1200 ppm 1-BP with 1-ABT treatment. The number of periodic acid-
Schiff (PAS)-positive round structures per seminiferous tubule was significantly increased at 250
ppm 1-BP in the absence of 1-ABT treatment and at 250 and 1200 ppm 1-BP in mice treated with
1-ABT. In 1-ABT treated mice, the numbers of retained elongated spermatids per tubule at 50 and
250 ppm 1-BP and PAS-positive round structures per tubule at 250 ppm were significantly lower
than in the mice not treated with 1-ABT. The study authors concluded that treatment of male mice
with 1-ABT, a general inhibitor of cytochrome P450s, inhibited the decreased epididymal sperm
count, decreased epididymal sperm motility, increased retained elongated spermatids per
seminiferous tubule, and increased PAS-positive round structures per seminiferous tubule that were
found in mice exposed to 50 and 250 ppm 1-BP in the absence of 1-ABT treatment.
J.2 Neurotoxicity
A number of laboratory animal studies report that both acute and repeated inhalational exposure to
high concentrations of 1-BP produce peripheral neurotoxicity indicated by changes in both
function and structure of the peripheral nervous system. The degree or severity of peripheral
neurotoxicity produced by 1-BP depends on the concentration as well as duration of exposure.
Most studies using concentrations of >1000 ppm report ataxia progressing to severely altered gait,
hindlimb weakness or loss of hindlimb control, convulsions, and death (e.g., (Banu et al.. 2007; Yu
et al.. 2001; Fueta et al.. 2000; Ichihara et al.. 2000a; Ohnishi et al.. 1999; ClinTrials. 1997a. b).
Concentrations of 400-1000 ppm produce neuropathological changes including peripheral nerve
degeneration, myelin sheath abnormalities, and spinal cord axonal swelling (Wang et al.. 2002; Yu
et al.. 2001; Ichihara et al.. 2000a).
Physiological and behavioral measures have been used to characterize and develop dose-response
data for this peripheral neurotoxicity. Motor nerve conduction velocity and latency measured in the
rat tail nerve were altered at >800 ppm with progressive changes observed from 4 to 12 weeks of
exposure (Yu et al.. 2001; Ichihara et al.. 2000a). These findings in rats agree with neurological
symptoms reported in exposed humans, including peripheral weakness, tingling in extremities, and
gait disturbances. The nerve conduction velocity endpoint that was altered in rats (Yu et al.. 2001;
Ichihara et al.. 2000a) is directly comparable to the increased latencies and lower conduction
velocity measured in a population of female factory workers exposed to 1-BP (Li et al.. 2010;
Ichihara et al.. 2004b).
Behavioral tests such as grip strength, landing foot splay, traction (hang) time, and gait score
provide dose-response data and appear somewhat more sensitive than neuropathology or
physiological changes. Ichihara et al. (2000a) reported progressively worsening effects over
12 weeks of exposure at 400 and 800 ppm including decreased hindlimb and forelimb grip
strength, and inability to walk on a slightly-sloped plane; exposure at 200 ppm significantly
decreased hindlimb grip only at 4 weeks and otherwise was without effect. Hindlimb grip was
preferentially decreased compared to forelimb as is often observed with peripheral neuropathy.
Similarly decreased hindlimb strength was reported by Banu et al. (2007) after 6 weeks of 1-BP
Page 415 of 486
-------
exposure at 1000 ppm (but not 400 ppm); these changes had not recovered at 14 weeks post
exposure. Honma et al. (2003) measured the time for a rat to hang onto a suspended bar, which
they called a traction test. The average time to hang appeared to be decreased following 21 days of
exposure to 50 ppm, and was significantly so with 200 and 1000 ppm; these changes were still
evident when animals were tested 7 days later. The ability to stay on a rotarod was not altered in
these rats, suggesting that the weakness is peripherally mediated.
Results reported following oral dosing with 1-BP are similar to those reported following inhalation
exposure. Over 16 weeks of dosing (200-800 mg/kg/d), Wang et al. (2012). reported progressively
decreased hindlimb grip strength, wider landing foot splay, and increased gait abnormalities. The
high-dose group was too debilitated to test after 14 weeks, but at that time their grip strength was
decreased by 42%, somewhat comparable to the 56% decrease reported with 13 weeks of 800 ppm
inhalational exposure (Ichihara et al.. 2000a). Rats exposed to the lowest concentration of 200
mg/kg/d showed less, but still statistically significant changes in gait and decreased (9%) hindlimb
grip strength. Subcutaneous administration of 455 or 1353 mg/kg/d (said to be equal to inhalation
of 300 or 1000 ppm) over a 4 week period also produced changes in tail motor nerve function
(Zhao et al.. 1999) similar to the effects reported by others following inhalation exposure.
Some behavioral assays conducted in rats exposed to 1-BP reflect involvement of central as well as
peripheral nervous systems. Increased motor activity levels were measured following inhalation of
50 or 200 ppm for three weeks (Honma et al.. 2003). Spatial learning and memory measured in a
Morris water maze was severely impaired while rats were receiving oral doses of 200 mg/kg/d and
greater (Guo et al.. 2015; Zhong et al.. 2013). Guo et al. (2015) also reported that these cognitive
deficits correlated with lowered levels of neuroglobin and glutathione depletion indicative of
oxidative stress in the same rats. During inhalational exposure, water maze performance was
impaired at concentrations of 200 ppm and above (Honma et al.. 2003). However, these
concentrations also produced neuromotor difficulties, which would interfere with performance of
the task. There were no changes in water maze performance when training was initiated after
exposure ended. Furthermore, there were no differences in memory of a passive avoidance task
when the initial learning took place before exposures began (Honma et al.. 2003).
A number of features reflecting CNS neurotoxicity have been reported for 1-BP. Brain pathology
has been reported in several, but not all, studies, which may be due to experimental differences
such as tissue sampling, staining, and measurement. Histological examination of the brain showed
widespread pathology at 1000 and 1600 ppm, and mild myelin vacuolization at 400 ppm, following
28 days of exposure (ClinTrials. 1997b); however, the same testing laboratory reported no
neuropathology with exposures up to 600 ppm for 13 weeks (ClinTrials. 1997a). In the cerebellum,
exposure at 400 ppm and higher produced degeneration of Purkinje cells (Mohideen et al.. 2013;
Ohnishi et al.. 1999) without morphological changes in the hippocampus (Mohideen et al.. 2013).
Similar exposure levels decreased noradrenergic but not serotonergic axonal density in frontal
cortex and amygdala (Guo et al.. 2015; Mohideen et al.. 2011). In contrast to these reports, no
degeneration was observed across several brain sections up to 800 ppm despite marked peripheral
and spinal cord changes in the same rats (Wang et al.. 2002; Ichihara et al.. 2000a). In two other
studies conducted in the same laboratory, one reported no histological or morphological changes in
Page 416 of 486
-------
brain following exposures up to 1250 ppm for 13 weeks (Sohn et al.. 2002) and another reported
no neuropathology after daily exposures of 1800 ppm for up to eight weeks (Kim et al.. 1999a).
even though in the latter study other indicators of neurotoxicity were observed.
Decreased absolute brain weight has been reported in several studies, both in the context of adult
exposures and long-term exposures during a 2-generation reproductive study. Studies involving
exposures from 4 to 12 weeks reported decreased brain weight at 800 and 1000 ppm (Subramanian
et al.. 2012; Wang et al.. 2003; Ichihara et al.. 2000a). Kim et al. (1999a) also reported decreased
brain weight at 300 ppm for 8 weeks, but only provided relative brain:body weight data. In the
parental generation of a 2-generation study, exposure for at least 16 weeks also produced brain
weight changes, with males being more sensitive (NOAEL=100 ppm, LOAEL=250 ppm) than
females (NOAEL=250 ppm) (WIL Research. 2001). The Fi generation, which was exposed during
gestation and at least 16 weeks after weaning, had lower brain weight at 100 ppm in males, and
again females were less sensitive (NOAEL=250 ppm). Histopathological evaluations in the WIL
study revealed no correlative macroscopic or microscopic alterations in unperfused brain tissue.
Two studies have measured brain weight and reported no effects: 1) (Wang et al.. 2002). in which
exposure was only 7 days and may not have been a sufficient exposure duration, and 2) the 13-wk
study of (ClinTrials. 1997a). even though the same laboratory reported decreased brain weight at
the same concentration with only 4 weeks of exposure.
Fueta and colleagues (Fueta et al.. 2007; Ueno et al.. 2007; Fueta et al.. 2004; Fueta et al.. 2002a;
Fueta et al.. 2002b; Fueta et al.. 2000). reported a series of studies using electrophysiological
measures of hippocampal slices (dentate gyrus and CA1 regions) from rats exposed to 1-BP for
four to 12 weeks. Concentrations of 400 ppm and higher showed disinhibition in paired-pulse
population spikes, and the effect was dependent on exposure concentration and duration. This
hyperexcitability appeared to be due to a reduction in feedback inhibition rather than a change in
excitatory synaptic drive. There was a moderate correlation with the level of bromide ion in the
brain. Pharmacological probes, proteins and receptor mRNA levels suggest that these effects are
related to actions on the GABA and NMDA neural systems, and/or intracellular signaling cascades
(Ueno et al.. 2007; Fueta et al.. 2004; Fueta et al.. 2002a; Fueta et al.. 2002b). A recent Society of
Toxicology presentation (abstract only available) reported similar effects in hippocampal slices
from 14-day old rat pups whose mothers were exposed to 400 or 700 ppm during gestation (Fueta
et al.. 2013).
A number of investigators have probed potential molecular mechanisms for some of these CNS
effects. Exposures of 200 ppm and greater produce changes in biomarkers and proteome
expressions suggesting alterations in the function and maintenance of neural and astrocytic cell
populations. Some of these include indicators of oxidative stress (reactive oxygen species,
glutathione depletion), ATP loss, protein damage, altered apoptotic signaling, neurotransmitter
dysregulation, decreased hippocampal neurogenesis, and others (Huang et al.. 2015; Mohideen et
al.. 2013; Zhang et al.. 2013; Zhong et al.. 2013; Huang et al.. 2012; Subramanian et al.. 2012;
Huang et al.. 2011; Yoshida et al.. 2007; Wang et al.. 2003; Wang et al.. 2002). Concentrations as
low as 50 ppm for three weeks were reported to decrease levels of the serotonin metabolite 5-
HIAA in frontal cortex and taurine in midbrain, while concentrations of 200 ppm and greater
Page 417 of 486
-------
impacted additional markers (protein levels, mRNA) of monoaminergic and amino acid
neurotransmitter systems (Zhang et al.. 2013; Mohideen et al.. 2009; Suda et al.. 2008; Ueno et al..
2007). Overall these data suggest several and perhaps overlapping cellular and molecular
mechanisms that could contribute to the functional and structural alterations reported for 1-BP.
(Zona et al.. 2016). citing studies from the literature, noted that the potential of 1-bromopropane
(1-BP) to induce neurotoxicity in mice had not been studied because 1-BP induced lethal
hepatotoxicity in mice before the appearance of potential overt evidence of neurotoxicity. To
develop a murine model of neurotoxicity, (Zona et al.. 2016) proposed treatment of mice with 1-
aminobenzotriazole (1-ABT), a general inhibitor of cytochrome P450s, to reduce severe
hepatotoxicity and allow studies on the effects of 1-BP on the mouse brain. A preliminary
experiment showed that subcutaneous (s.c) or intraperitoneal injections of male C57BL/6J mice
with 50 mg/kg 1-ABT twice daily for three days inhibited CYP2E1 activity by 62-64% in the brain
and by 92-96% in the liver, compared with values in saline-injected control mice. Since the route
of injection had no significant effect on the extent of CYP2E1 activity inhibition, the s.c. route of
1-ABT administration was chosen for model development to minimize potential for damage of
internal organs. For the main study, groups of six 8-week-old male C57BL/6J mice were exposed
whole-body to 1-BP for 8 hours/day for 4 weeks at vapor concentrations of 0, 50, or 250 ppm with
s.c. injections of saline before and after each inhalation exposure and at 0, 50, 250, or 1200 ppm
with s.c. injections of 50 mg 1-ABT/kg in saline before and after each inhalation exposure (100 mg
1-ABT/kg-day). The only treatment-related effect on body weight was significant loss of body
weight on day 28 in mice exposed to 1200 ppm 1-BP/l-ABT. In mice not treated with 1-ABT,
mild histological changes in hepatocytes included centrilobular degeneration and nuclear and
cytoplasmic changes at 50 ppm 1-BP. Exposure to 250 ppm without 1-ABT produced severe
pathological changes in the liver including macroscopic and microscopic liver necrosis,
hemorrhage, and foci of hepatocyte degeneration. In contrast, no serious histopathological changes
were found in the livers of 1-ABT-treated mice that were exposed to 50, 250, or 1200 ppm 1-BP.
Absolute mean liver weights were significantly decreased at 50 ppm 1-BP in the absence of 1-ABT
treatment and at 250 and 1200 ppm 1-BP in animals treated with 1-ABT. Absolute mean brain
weight was significantly lower than control in the group treated with 1-ABT and exposed to 1200
ppm 1-BP, but brain weights were unaffected in other exposure groups. Cerebral cortex and
hippocampal expression of Ran, GRP78, y-enolase, and c-Fos proteins was determined by western
blotting analysis in all treated mouse groups. Studies from the literature showed that expression of
these four proteins was altered in brain tissues of rats exposed to 1-BP in the absence of treatment
with 1-ABT. In the male C57BL/6J mice treated with 1-ABT, hippocampal Ran expression and
cortex GRP78 expression were significantly increased at 1200 ppm 1-BP and hippocampal Ran
expression was significantly increased at 250 ppm 1-BP. No changes in Ran or GRP78 expression
occurred in other mouse groups, including those treated with 50 or 250 ppm 1-BP in the absence of
1-ABT treatment. No treatment-related changes were found in the expression of y-enolase or c-Fos
in the hippocampus or cerebral cortex. The treatment of mice in this study with 1-ABT, a general
inhibitor of cytochrome P450s, reduced the severe hepatotoxicity/lethality of 1-BP to mice, thus
allowing mouse survival at 1-BP exposure concentrations as high as 1200 ppm for 8 hours/day for
28 days and the study of the effects of 1-BP on the mouse brain.
Page 418 of 486
-------
J.3 Human Case Reports
Several case studies have reported various neurological effects in workers exposed to 1-BP
(Samukawa et al.. 2012; CDC. 2008; Maiersik et al.. 2007; Raymond and Ford. 2007; Ichihara et
al.. 2002; Sclar. 1999). Some of the neurological effects experienced by workers included
peripheral neuropathy, muscle weakness, pain, headaches, numbness, gait disturbance, confusion,
ocular symptoms, slowed mental activity, and dizziness. In some instances, the effects were still
observed many months after exposure had ceased or had been reduced.
Workers described in the case reports were exposed to 1-BP in the following activities: metal
cleaning, circuit board cleaning, and gluing foam cushions or furniture. In almost all of the cases
reported in the table below, personal protective equipment was not used and air concentrations of
1-BP, when available, were greater than 100 ppm. Bromide levels, both serum and in a few cases,
urinary, were provided in some of the studies and are included in the table below. Bromide
concentrations have been used as a biomarker of exposure to 1-BP. A description of the use of
bromide levels and the investigation into using other biomarkers of exposure are included in
Section 2.2.
(Raymond and Ford. 2007) reported high levels of urinary arsenic, as well as serum bromide, in the
workers described in their case report of four employees who required hospitalization, suggesting
arsenic and bromide synergism. All four of the workers had total (organic and inorganic) urinary
arsenic levels greater than 200 |ig/L, but the source of the arsenic could not be identified. NIOSH
reported on these 4 employees in a HHE on a plant where workers applied spray adhesive to
cushions, and concluded that the exposure was likely not occupational and could not have been the
sole cause of ataxia and paresthesia that the four hospitalized workers experienced
Table Apx J-l. Case Reports on 1-BP
Reference1
# Cases
Primary Symptoms
Activity
Air levels
Serum
Bromide
levels
(mg/dL)2
(Maiersik et
al.. 2007)
6
Headache, nausea,
dizziness, lower
extremity numbness,
pain, paresthesia,
difficulty
walking/balance
Foam cushion
gluing at
furniture plant
(glue contained
70% 1-BP)
130 ppm (range,
91-176);
TWA 108 ppm
(range, 92-127)
Peak range:
44-170
(Sclar. 1999)
1
Peripheral neuropathy,
weakness of lower
extremities and hand,
numbness, dysphagia
Metal stripping
(degreasing and
cleaning)
Not available
Not available
(CDC. 2008)
2
Confusion, dysarthria,
dizziness, paresthesias,
ataxia;
Headache, nausea,
dizziness, malaise
Cleaning circuit
boards (spray)
Solvent in dry
cleaning
178 ppm
48 mg/dL and
not available
for case #2
Page 419 of 486
-------
Table Apx J-l. Case Reports on 1-BP
Serum
Reference1
# Cases
Primary Symptoms
Activity
Air levels
Bromide
levels
(mg/dL)2
75-250x
background
levels
(Samukawa et
1
Muscle weakness, pain.
Metal cleaning
553 ppm, mean
58 ng/mL
al.. 2012)
numbness in lower
extremities, gait
disturbance
TWA (range,
353-663)
(peak)
(Raymond and
4
Dizziness, anorexia.
Gluing in
Mean 107 ppm
3.0 -12.5
Ford. 2007)
dysesthesias, nausea.
furniture
(range, 58-254
mEq/L (100
(4 cases from
numbness, ocular
making
ppm) collected
mg/dL)
NIOSH
symptoms, unsteady
9 months after
(2003a)
gait, weakness, weight
workers became
Arsenic levels
HHE report on
loss
ill
> 200 ng/L for
Marx
all 4
Industries)
employees3
(NIOSH.
16
Headache, anxiety.
Spray
1999 (16
Serum GM:
2003a)
(incl. 4
feeling "drunk,"
application of
personal
4.8 mg/dL
from
numbness and "pins and
glue to
breathing zone
(2.7-43.5;
Raymond
needles" sensation in
polyurethane
samples): GM
n=39);
(2007)
legs and feet
foam to make
cushions
81.2 ppm
(range,
18-254 ppm);
2001 (13 PBZ
samples):
GM 45.7 ppm
(range, 7-281
ppm)
Urinary: 46.5
mg/dL (15.4-
595.4, n=40)
Includes both
exposed and
unexposed
workers
(Ichihara et al..
3
Staggering gait.
Spray
Mean 133 ppm.
Not available
2002)
paresthesia in lower
extremities, numbness in
legs, headache, urinary
incontinence, deer in
vibration sense in legs
application of
glue to
polyurethane
foam to make
cushions
(range, 60-261
ppm daily
TWA); avg over
11 days 133 ±
67 ppm~after
ventilation
improved
Biomarker Studies also Containing Case Report Data
(Hanlev et al..
13
(focused on exposure
Spray
Mean
Urinary: 190
2006b)
and urinary Br)
application of
glue to
polyurethane
foam to make
cushions
92 ppm (range,
45-200 ppm)
(43-672;
composite of 2
days)
(Ichihara et al..
24 female
Nose, throat, eye
1-BP production
3.3-90.2 ppm
Urinary
2004b;
13 male
irritation; malaise.
No severe
bromide
Ichihara et al..
China
headache, dizziness
neurological
measured but
2004a)
effects
not reported
Page 420 of 486
-------
Table Apx J-l. Case Reports on 1-BP
Reference1
# Cases
Primary Symptoms
Activity
Air levels
Serum
Bromide
levels
(mg/dL)2
<170 ppm
1 EPA has not published systematic review criteria for reports/case studies, therefore data quality evaluation for these
reports are not available
2Serum bromide unless otherwise indicated; Reference ranges vary by report
3Arsenic Reference range: <0.06
J.4 Human Epidemiology Studies
The 1-BP database includes three epidemiological studies of workers occupationally exposed to 1-
BP (Li et al.. 2010; Toraason et al.. 2006; Ichihara et al.. 2004b); two of the studies report
neurologic effects and the third analyzed for DNA damage in workers' leukocytes. The evaluation
of 1-BP epidemiology studies by each of the five aspects of study design - study population
characteristics and representativeness, exposure measures, outcome measures, confounding, and
analysis - is discussed below; additional information regarding the data evaluation results for
individual studies can be found in the Draft Risk Evaluation for 1-Bromopropane (1-BP),
Systematic Review Supplemental File: Data Quality Evaluation of Human Health Hazard Studies.
EPA-HQ-OPPT-2019-0235 (EPA, 2019o). Twenty-three female workers involved in 1-BP
production in China were surveyed in 2001 and compared with age-matched controls from a beer
factory located in the same city (Ichihara et al.. 2004b). The study authors did not report the
method of recruitment. Neurological tests (vibration sensation, electrophysiologic studies), blood
tests, neurobehavioral tests and postural sway tests were administered. Passive sampling indicated
individual exposure levels ranging from 0.34 - 49.2 ppm in an 8-hour shift (median 1.61 ppm;
geometric mean 2.92 ppm). Some of the employees in this plant were also exposed to 2-BP and
were analyzed separately. Although some of the neurologic measures indicated reduced function in
exposed workers compared to controls, because of the past exposures to 2-BP and the small
number of cases who entered the study after 2-BP was no longer used (n= 12 pairs), it was difficult
to interpret the results of this study. In workers who were employed at the plant after 2-BP was no
longer used, Benton visual memory test scores, POMS depression, and POMS fatigue were
significantly different. It is not clear whether this indicates a lack of power to detect differences in
the larger group or whether the exposure to 2-BP affected the results.
As a follow-up to the Ichihara study (Ichihara et al.. 2004b) described above, (Li et al.. 2010)
combined data from three 1-BP production facilities in China to analyze a larger sample of
workers. Sixty female and 26 male workers and controls from other types of factories matched by
age, sex and geographic region were analyzed from four time periods (2001, 2003, 2004, 2005).
Data were collected over 3 days between 2001 and 2005. The authors did not describe the
recruitment process, and it is not clear whether the same workers included in the Ichihara 2004
study were recruited for this study. The authors reported that none of the workers had a history of
diabetes.
Page 421 of 486
-------
Exposures were measured for each plant using passive samplers. Exposure was measured either
once or twice over 8 or 12 hour work shifts. TWA exposure concentrations to 1-BP ranged from
0.07-106.4 ppm for female workers and 0.06-114.8 ppm for male workers. It was reported that
none of the workers wore gloves or masks in the plant. However, the authors later clarified that
some workers wore gloves (Ichihara et al.. 2011). Employees were placed into low-, medium-, and
high-exposure groups (for females) to include equal numbers. Median exposures for the three
groups (n=20 per group) were 1.28, 6.60 and 22.58 ppm for females and 1.05 (low) and 12.5 (high)
ppm for males (n=13 per group). Ambient exposure levels varied by job and by plant and were
collected in different years for each plant. For example, the ambient concentrations of "raw product
collection" were more than 3 times higher at the Yancheng plant (analyzed in 2003) than at the
Yixing plant (Li et al.. 2010).
Clinical chemistries were obtained, and electrophysiological studies and neurological and
neurobehavioral tests were conducted for each employee. A single neurologist performed most of
the neurological assessments except for those collected in 2004 from one plant, which included 5
female workers. Electrophysiological tests conducted included: motor nerve conduction velocity,
distal latency (DL), F-wave conduction velocity in the tibial nerve, sensory nerve conduction
velocity in the sural nerve (SNCV), and amplitude of the electromyogram induced by motor nerve
stimulation, F-wave, and potential of sensory nerve. Vibration sense, reflex, and muscle strength
were measured using a tuning fork on the big toe. Neurobehavioral tests and blood tests were also
performed.
In regression analyses, the authors reported a statistically significant increase (p<0.05) in mean
tibial motor distal latency and a decrease in mean sural nerve conduction velocity in women in the
middle exposure group only (compared to controls). Statistically significant decreased vibration
sense in toes (vibration loss) was reported in all exposure groups compared to controls. In addition,
thyroid stimulating hormone (TSH) was significantly different in the middle and high exposure
groups compared to controls and FSH in low and medium exposure groups in females. Red blood
cell count was significantly decreased in all exposure groups compared to controls in females. In
males, the only statistically significant difference between the high exposure group and controls
was for blood urea nitrogen.
Analyses of cumulative exposure measures (exposure level x duration) indicated statistically
significant (/K0.05) increases in vibration sense in toes in females across all exposure levels when
compared to controls (5.6 ± 4.3, 6.4 ± 3.8, and 6.5 ±3.4 sees, mean ± SD for low, medium and
high cumulative exposure groups, respectively). In females, only the high cumulative exposure
group for tibial motor DL was statistically higher than in controls and only the low cumulative
exposure group for sural NCV. Analyses to adjust for other factors that could influence vibration
loss (examining neurologist, age, height, body weight, alcohol consumption) were conducted using
analysis of covariance in female workers. The effect of 1-BP exposure on vibration loss was
significant (p = 0.0001 or p = 0.0002) based on cumulative exposures as well as exposures not
considering duration of exposure, respectively, but the effect of examining neurologist was also
significant (p < 0.0001).
Page 422 of 486
-------
Both of the neurological studies described above (Li et al.. 2010; Ichihara et al.. 2004b) showed
neurological effects related to 1-BP exposure. The co-exposures to 2-BP and the small sample size
of workers exposed only to 1-BP was a limitation in the Ichihara et al. 2004 study. Li et al. (2010)
selected workers exposed to 1-BP from 3 plants to include more study participants; however, the
exposure data reported by plant were limited, the job activities were somewhat different between
plants (but for those jobs with similar activities between plants, some exposures were more than 3
times higher at one plant than another), and ambient exposure levels of 1-BP and 2-BP reported by
job and by plant were collected in different years for each plant. Several of these issues could lead
to exposure misclassification of the workers. TWAs (8- and 12- hour) were used to assign exposure
groups, based on either 1 or 2 samples. Using the TWA does not account for the fluctuations or
potential peaks that may have occurred during the shift. In addition, the median exposure level of
the high exposure group for females was 22.58 ppm but the range was 15.28-106.4 ppm, indicating
that some of the workers were exposed to levels much higher than the lowest exposed workers in
that group. In addition, the cumulative exposure measures were based on only 1-3- day
measurements of individual exposure levels.
Skin temperature is important when conducting electrophysiological studies; however, the only
control for temperature in this study was to acclimate study participants to 24° C in a room for 30
minutes. Individual skin temperatures should have been taken at the site of the test (on the foot)
because the results are affected by temperature. Vibration sense can be influenced by BMI, but it
was not reported or controlled in the study. As acknowledged in the report by the study authors,
vibration sense is inherently imprecise (based on the sensitivity of the subject relative to the
examiner). Evidence of a high degree of variability was shown in the large standard deviations
reported for vibration sense in females (2.9 ± 3.9, mean ± SD for controls; 5.6 ± 4.4, low exposure
group). Other than RBC, only vibration sense in females using the cumulative exposure measure
was concentration-dependent. RBC in females could have been influenced by other factors (e.g.,
menstruation, dehydration) that were not examined in the study.
Toraason et al. (2006) analyzed DNA damage in peripheral leukocytes of workers exposed to 1-BP
during spray application of adhesives in the manufacture of foam cushions for upholstered
furniture. Sixty-four workers (18 males, 46 females) at two plants were included in the analysis.
There were no unexposed groups. Fifty of 64 workers wore personal air monitors for 1-3 days.
Workers employed as sprayers had the highest exposures; 1-BP 8-hr TWA concentrations were
substantially higher (4 times) for sprayers at one of the plants than the other. TWA exposures
ranged from 0.2 to 271 ppm across both plants. DNA damage was assessed using comet assay.
DNA damage was measured by tail moment in leukocytes of workers. At both the start and end of
the work week, DNA leukocyte damage was higher for sprayers than non-sprayers but the
increases were not statistically significant. In addition, the facility with lower exposures had higher
measures of DNA damage than the higher exposure facility at the beginning of the week but not
the end. Tail moment dispersion coefficients did not indicate an exposure-response relationship.
Three different biomarkers of exposure, 1-BP TWA concentrations and serum and urinary bromide
levels, were evaluated in multivariate analyses. After controlling for various potential confounders,
starting and ending work week comet tail moments in leukocytes were significantly associated
Page 423 of 486
-------
with serum bromide quartiles and ending work week values of 1-BP TWA concentrations. None of
the models that examined associations between DNA damage and dispersion coefficients was
statistically significant. There was a slight risk for DNA damage in workers' leukocytes in vitro in
workers exposed to 1-BP but the results of the in vivo data were not consistent.
Page 424 of 486
-------
TableApx J-2. Summary of the Toxicological Database for 1-BP
Target
Organ/
System
Study Type
Species/
Strain/Sex
(Number/
group)1
Exposure
Route
Doses/
Concentrations2
Duration3
Effect Dose/
Concentration
(ppm or
mg/kg-day)4
(Sex)
Effect5
Reference6
Data Quality
Evaluation78
Mortality
Acute
Rat, Wistar,
MZF
(n=10/group)
Inhalation
0, 6040, 7000,
7400 or 8500
ppm
4 hours
LCso = 7000
Mortality
(acute
inflammatory
response and
alveolar
edema)
(Elf
Atochem.
1997)
N/A
Mortality
Acute
Rat, Sprague-
Dawley, M/F
(n=10/group)
Inhalation,
whole body,
vapor
0, 511,000,
13,000, 15,000
or 17,000 ppm
4 hours
LCso = 14,374
Mortality
(Kim et al..
1999a)
N/A
Mortality
Chronic
Rat, F344/N,
M/F
(n=100/group)
Inhalation,
whole body,
vapor
0, 125, 250 or
500 ppm
6.2 hours/day,
5 days/week
for 105 weeks
NOAEL= 250
(M)
Decreased
survival
(NTP,
2011a)
High
Mortality
Short-term
Mouse,
B6C3F1, M/F
(n=10/group)
Inhalation,
whole body,
vapor
0, 125, 250, 500,
1000 or 2000
ppm
6.2 hours/day,
5 days/week
for 17 days
NOAEL= 250
Decreased
survival
(NTP,
2011a)
High
Mortality
Short-term
Mouse,
C57BL/6J,
DBA/2J and
BALB/cA,
M
(n=6/strain/gro
up)
Inhalation,
whole body,
vapor
0, 50, 110 or 250
ppm
8 hours/day,
7 days/week
for 4 weeks
NOAEL= 110
Mortality (two
of three strains
affected)
(Liu et al..
2009)
High
Mortality
Short-term/
Subchronic
Mouse,
B6C3F1, F
(n=5-8/group)
Inhalation,
whole body,
vapor
0, 125, 250 or
500 ppm
6.2 hours/day,
5 days/week
for 4 or 10
weeks
NOAEL= 250
(F)
Mortality
(first week on
study)
(Anderson et
al.. 2010)
Medium
Mortality
Chronic
Mouse,
B6C3F1, M/F
(n=20/group)
Inhalation,
whole body,
vapor
0, 62.5, 125, 250
or 500 ppm
6.2 hours/day,
5 days/week
for 14 weeks
NOAEL= 250
Decreased
survival rate
(NTP,
2011a)
High
Page 425 of 486
-------
Target
Organ/
System
Study Type
Species/
Strain/Sex
(Number/
group)1
Exposure
Route
Doses/
Concentrations2
Duration3
Effect Dose/
Concentration
(ppm or
mg/kg-day)4
(Sex)
Effect5
Reference6
Data Quality
Evaluation7'8
Mortality
Acute
Rat, Sprague-
Dawley, F
(n=10/group)
Oral
0 or 2000 mg/kg
Single
exposure
LD50 ^ 2000
mg/kg (F)
Mortality
(Elf
Atochem.
1993a)
N/A
Body weight
Acute
Rat, M
(n=10/group)
Inhalation
0, 6040, 7000,
7400 or 8500
ppm
4 hours
NOAEL= 8500
(M)
No effects on
body weight
(Elf
Atochem.
1997)
N/A
Body weight
Short-term
Rat, Wistar, M
(n=8/group)
Inhalation,
whole body,
vapor
0, 200, 400 or
800 ppm
8 hours/day
for 7 days
NOAEL= 400
(M)
Decreased
body weight
(Wans et al..
2002)
N/A
Body weight
Short-term
Rat, Wistar, M
(n=6/group)
Inhalation,
whole body,
vapor
0, 400, 800 ot
1000 ppm
8 hours/day
for 7 days
NOAEL= 400
(M)
Decreased
body weight
(Zhang et
al.. 2013)
High
Body weight
Short-term
Rat, F344/N,
MZF
(n=10/group)
Inhalation,
whole body,
vapor
0, 125, 250, 500,
1000 or 2000
ppm
6.2 hours/day,
5 days/week
for 16 days
NOAEL= 1000
Decreased
body weight
(NTP,
2011a)
High
Body weight
Short-term
Rat, F344, M
(n=5/group)
Inhalation,
whole body,
vapor
0, 10, 50, 200 or
1000 ppm
8 hours/day,
7 days/week
for 3 weeks
NOAEL= 50
(M)
Increased
body weight
(Honma et
al.. 2003)
Low
Body weight
Short-term
Rat, F344, F
(n=7-8/group)
Inhalation,
whole body,
vapor
0, 50, 200 or
1000 ppm
8 hours/day,
7 days/week
for 3 weeks
NOAEL= 1000
(F)
No effects on
body weight
(Sekiguchi
et al.. 2002)
N/A
Body weight
Short-term
Rat
(n=20/group)
Inhalation
0, 398, 994 or
1590 ppm
6 hours/day,
5 days/week
for 4 weeks
NOAEL= 398
Decreased
weight gain
f CI inT rials.
1997b)
N/A
Body weight
Short-term
Rat, Wistar-ST,
M
(n=12/group)
Inhalation,
whole body,
vapor
0, 400, 800 or
1000 ppm
8 hours/day,
7 days/week
for 4 weeks
NOAEL= 800
(M)
Decreased
body weight
(Subramania
n et al..
2012)
N/A
Body weight
Subchronic
Rat, Wistar, M
(n=9/group)
Inhalation,
whole body,
vapor
0 or 1000 ppm
8 hours/day,
7 days/week
for 5 or
7 weeks
LOAEL= 1000
(M)
Decreased
body weight
(Yu et al..
2001)
Medium
Page 426 of 486
-------
Target
Organ/
System
Study Type
Species/
Strain/Sex
(Number/
group)1
Exposure
Route
Doses/
Concentrations2
Duration3
Effect Dose/
Concentration
(ppm or
mg/kg-day)4
(Sex)
Effect5
Reference6
Data Quality
Evaluation7'8
Body weight
Subchronic
Rat, Wistar, M
Inhalation,
0, 400, 800 or
8 hours/day.
NOAEL= 400
Decreased
(Banu et al..
N/A
(n=24/group)
whole body,
vapor
1000 ppm
7 days/week
for 6 weeks
(M)
body weight
2007)
Body weight
Subchronic
Rat, Sprague-
Inhalation,
0, 50, 300 or
6 hours/day.
NOAEL= 300
Decreased
(Kim et al..
N/A
Dawley, M/F
whole body.
1800 ppm
5 days/week
body weight
1999b)
(n=20/group)
vapor
for 8 weeks
Body weight
Subchronic
Rat, Wistar, M
Inhalation,
0, 200, 400 or
8 hours/day.
NOAEL= 200
Decreased
(Ichihara et
High
(n=8-9/group)
whole body,
vapor
800 ppm
7 days/week
for 12 weeks
(M)
body weight
al.. 2000a)
Body weight
Subchronic
Rat, Wistar, M
Inhalation,
0, 200, 400 or
8 hours/day.
NOAEL= 1200
Decreased
(Wans et al..
N/A
(n=9/group)
whole body,
vapor
800 ppm
7 days/week
for 12 weeks
(M)
body weight
2003)
Body weight
Subchronic
Rat, Wistar, F
Inhalation,
0, 200, 400 or
8 hours/day.
NOAEL= 400
Decreased
(Yamada et
High
(n=10/group)
whole body,
vapor
800 ppm
7 days/
week for up to
12 weeks
(F)
body weight
al.. 2003)
Body weight
Chronic
Rat, Albino,
Inhalation,
0, 100, 200, 400
6 hours/day.
NOAEL= 600
No effects on
(ClinTrials.
High
M/F
whole body.
or 600 ppm
5 days/
body weight
1997a)
(n=30/group)
vapor
week for 13
weeks
Body weight
Chronic
Rat, Sprague-
Inhalation,
0, 200, 500 or
6 hours/day.
NOAEL= 1250
No effects on
(Solinet al..
N/A
Dawley, M/F
whole body.
1250 ppm
5 days/week
body weight
2002)
(n=20/group)
vapor
for 13 weeks
Body weight
Chronic
Rat, F344/N,
Inhalation,
0, 62.5, 125, 250
6.2 hours/day.
NOAEL= 500
Decreased
(NTP.
High
M/F
whole body.
or 1000 ppm
5 days/week
(M)
body weight
2011a)
(n=20/group)
vapor
for 14 weeks
Body weight
Chronic
Rat, F344/N,
Inhalation,
0, 125, 250 or
6.2 hours/day.
NOAEL= 500
No effects on
(NTP.
High
M/F
whole body.
500 ppm
5 days/week
body weight
2011a)
(n=100/group)
vapor
for 105 weeks
Body weight
Developme
Rat, Albino
Inhalation,
0, 100, 199, 598
6 hours/day on
NOAEL= 100
Decreased
(Huntingdon
N/A
ntal
Crl:CD(SD)IG
S BR, F
(n=10/group)
whole body,
vapor
or 996 ppm
GDs 6-19
and lactation
days 4-20
(F)
body weight
gain during
gestation
Life
Sciences.
1999)
Page 427 of 486
-------
Target
Organ/
System
Study Type
Species/
Strain/Sex
(Number/
group)1
Exposure
Route
Doses/
Concentrations2
Duration3
Effect Dose/
Concentration
(ppm or
mg/kg-day)4
(Sex)
Effect5
Reference6
Data Quality
Evaluation7'8
Body weight
Developme
Rat, F
Inhalation
0, 103, 503 or
6 hours/day on
NOAEL= 103
Decreased
(Huntingdon
N/A
ntal
(n=25/group)
1005 ppm
GDs 6-19
(F)
body weight
gain during
gestation
Life
Sciences.
2001)
Body weight
Developme
Rat, Wistar-
Inhalation,
0, 100, 400 or
8 hours/day
NOAEL= 400
Decreased
(Furuhashi
N/A
ntal
Imamichi, F
(n=10/group)
whole body,
vapor
800 ppm
during
gestation (GDs
0-20)
and lactation
(PNDs 1-20)
(F)
body weight at
PND 21
et al.. 2006)
Body weight
Repro-
Rat,
Inhalation,
0, 100, 250, 500
6 hours/day
NOAEL= 250
Decreased
(WIL
High
ductive/
Crl:CD(SD)IG
whole body.
or 750 ppm
during pre-
(F)
body weight
Research.
Develop-
SBRM/F
vapor
mating
(Fo and Fi
2001)
mental
(n=50
FO/group, 49-
50 F1
adults/group/ge
neration; 30-47
F1
weanlings/grou
p; 30-44 F2
weanlings/grou
P)
(>70 days),
through
mating, and
until sacrifice
in males; or
until GD 20
and from PND
5 until
weaning of
offspring
(~PND 21) in
females
adults)
Body weight
Short-term
Mouse,
Inhalation,
0, 125, 250, 500,
6.2 hours/day.
NOAEL= 500
Decreased
(NTP.
High
B6C3F1, M/F
whole body.
1000 or 2000
5 days/week
(M)
body weight
2011a)
(n=10/group)
vapor
ppm
for 17 days
gain
Page 428 of 486
-------
Target
Organ/
System
Study Type
Species/
Strain/Sex
(Number/
group)1
Exposure
Route
Doses/
Concentrations2
Duration3
Effect Dose/
Concentration
(ppm or
mg/kg-day)4
(Sex)
Effect5
Reference6
Data Quality
Evaluation7'8
Body weight
Short-term
Mouse,
C57BL/6J,
DBA/2J and
BALB/cA,
M
(n=6/strain/gro
up)
Inlialation,
whole body,
vapor
0, 50, 110 or 250
ppm
8 hours/day,
7 days/ week
for 4 weeks
NOAEL= 250
(M)
No effects on
body weight
(Liu et al..
2009)
High
Body weight
Short-term/
Subchronic
Mouse,
B6C3F1, F
(n=5-8/group)
Inlialation,
whole body,
vapor
0, 125, 250 or
500 ppm
6.2 hours/day,
5 days/week
for 4 or
10 weeks
LOAEL= 125
(F)
Decreased
body weight
(Anderson et
al.. 2010)
Medium
Body weight
Chronic
Mouse,
B6C3F1, M/F
(n=20/group)
Inlialation,
whole body,
vapor
0, 62.5, 125, 250
or 500 ppm
6.2 hours/day,
5 days/week
for 14 weeks
NOAEL= 500
No effects on
body weight
(NTP,
2011a)
High
Body weight
Chronic
Mouse,
B6C3F1, M/F
(n=100/group)
Inlialation,
whole body,
vapor
0, 62.5, 125 or
250 ppm
6.2 hours/day,
5 days/week
for 105 weeks
NOAEL= 250
No effects on
body weight
(NTP,
2011a)
High
Body weight
Acute
Rat
(n=10/group)
Oral
0 or 2000 mg/kg
Single
exposure
NOAEL= 2000
mg/kg
No effects on
body weight
(Elf
Atochem.
1993a)
Body weight
Short-term
Rat, Wistar, M
(n=10/group)
Oral,
gavage
(corn oil
vehicle)
0, 200, 400 or
800 mg/kg-day
12 days
NOAEL= 400
mg/kg-day (M)
Decreased
final body
weight; used
for weight of
evidence; no
route-to-route
extrapolation
(Zhone et
al.. 2013)
Low
Body weight
Short-term
Rat, Sprague-
Dawley, M
(n=7/group)
Intra-
peritoneal
0 or 1000
mg/kg-day
14 days
LOAEL= 1000
mg/kg-day (M)
Decreased
body weight
(Xin et al..
2010)
N/A
Body weight
Chronic
Rat, M
(n=10/group)
Oral
0, 200, 400 or
800 mg/kg-day
16 weeks
NOAEL= 400
mg/kg-day (M)
Decreased
body weight
(Wans et al..
2012)
N/A
Page 429 of 486
-------
Target
Organ/
System
Study Type
Species/
Strain/Sex
(Number/
group)1
Exposure
Route
Doses/
Concentrations2
Duration3
Effect Dose/
Concentration
(ppm or
mg/kg-day)4
(Sex)
Effect5
Reference6
Data Quality
Evaluation7'8
Body weight
Short-term
Rat, Wistar, M
Oral,
0, 100, 200,
12 days
NOAEL= 400
Decreased
(Guo et al..
High
(n=14/group)
gavage
400 or
800 mg/kg-day
mg/kg-day (M)
body weight
2015)
Body weight
Acute
Mouse,
Oral,
0, 200, 500 or
Single
NOAEL= 1000
No effects on
(Lee et al..
N/A
BALB/c, F
gavage
1000 mg/kg
exposure;
mg/kg (F)
body weight
2007)
(n=5/group)
(corn oil
vehicle)
necropsy after
6, 12, 24 or
48 hours
Cardio-
Subchronic
Rat, Wistar, M
Inhalation,
0, 200, 400 or
8 hours/day.
NOAEL= 800
No effects on
(Ichihara et
High
vascular
(n=8-9/group)
whole body,
vapor
800 ppm
7 days/ week
for 12 weeks
(M)
heart weight
or liisto-
pathology
al.. 2000b)
Cardio-
Subchronic
Rat, Sprague-
Inhalation,
0, 50, 300 or
6 hours/day.
NOAEL= 1800
No effects on
(Kim et al..
N/A
vascular
Dawley, M/F
(n=20/group)
whole body,
vapor
1800 ppm
5 days/ week
for 8 weeks
heart weight
or liisto-
pathology
1999a)
Cardio-
Chronic
Rat, Albino,
Inhalation,
0, 100, 200, 400
6 hours/day.
NOAEL= 600
No effects on
(ClinTrials.
High
vascular
M/F
(n=30/group)
whole body,
vapor
or 600 ppm
5 days/ week
for 13 weeks
heart weight
or liisto-
pathology
1997a)
Cardio-
Chronic
Rat, F344/N,
Inhalation,
0, 62.5, 125,
6.2 hours/day.
NOAEL= 1000
No effects on
(NTP.
High
vascular
M/F
(n=20/group)
whole body,
vapor
250, 500 or 1000
ppm
5 days/week
for 14 weeks
heart weight
2011a)
Cardio-
Chronic
Rat, F344/N,
Inhalation,
0, 125, 250 or
6.2 hours/day.
NOAEL= 500
No effects on
(NTP.
High
vascular
M/F
(n=100/group)
whole body,
vapor
500 ppm
5 days/week
for 105 weeks
histopathology
2011a)
Cardio-
Short-term
Mouse,
Inhalation,
0, 125, 250, 500,
6.2 hours/day.
NOAEL= 2000
Decreased
(NTP.
High
vascular
B6C3F1, M/F
(n=10/group)
whole body,
vapor
1000 or 2000
ppm
5 days/week
for 17 days
(M)
absolute and
relative heart
weight
2011a)
Page 430 of 486
-------
Target
Organ/
System
Study Type
Species/
Strain/Sex
(Number/
group)1
Exposure
Route
Doses/
Concentrations2
Duration3
Effect Dose/
Concentration
(ppm or
mg/kg-day)4
(Sex)
Effect5
Reference6
Data Quality
Evaluation7'8
Cardio-
Chronic
Mouse,
Inhalation,
0, 62.5, 125, 250
6.2 hours/day.
NOAEL= 500
No effects on
(NTP.
High
vascular
B6C3F1, M/F
(n=20/group)
whole body,
vapor
or 500 ppm
5 days/week
for 14 weeks
heart weight
or liisto-
pathology
2011a)
Cardio-
Chronic
Mouse,
Inhalation,
0, 62.5, 125 or
6.2 hours/day.
NOAEL= 250
No effects on
(NTP.
High
vascular
B6C3F1, M/F
(n=100/group)
whole body,
vapor
250 ppm
5 days/week
for 105 weeks
histopathology
2011a)
Skin
Chronic
Rat, Albino,
Inhalation,
0, 100, 200, 400
6 hours/day.
NOAEL= 600
No effects on
(ClinTrials.
High
M/F
whole body.
or 600 ppm
5 days/ week
histopathology
1997a)
(n=30/group)
vapor
for 13 weeks
Skin
Chronic
Rat, F344/N,
Inhalation,
0, 62.5, 125,
6.2 hours/day.
NOAEL= 1000
No effects on
(NTP.
High
M/F
whole body.
250, 500 or 1000
5 days/week
histopathology
2011a)
(n=20/group)
vapor
ppm
for 14 weeks
Skin
Chronic
Rat, F344/N,
Inhalation,
0, 125, 250 or
6.2 hours/day.
NOAEL= 500
No effects on
(NTP.
High
M/F
whole body.
500 ppm
5 days/week
histopathology
2011a)
(n=100/group)
vapor
for 105 weeks
Skin
Chronic
Mouse,
Inhalation,
0, 62.5, 125, 250
6.2 hours/day.
NOAEL= 500
No effects on
(NTP.
High
B6C3F1, M/F
whole body.
or 500 ppm
5 days/week
histopathology
2011a)
(n=20/group)
vapor
for 14 weeks
Skin
Chronic
Mouse,
Inhalation,
0, 62.5, 125 or
6.2 hours/day.
NOAEL= 250
No effects on
(NTP.
High
B6C3F1, M/F
whole body.
250 ppm
5 days/week
histopathology
2011a)
(n=100/group)
vapor
for 105 weeks
Endocrine
Short-term
Rat, Wistar, M
Inhalation,
0, 400, 800 or
8 hours/day for
NOAEL= 1000
No effects on
(Zhane et
High
(n=6/group)
whole body,
vapor
1000 ppm
7 days
(M)
adrenal gland
weight or
plasma
corticosterone
al.. 2013)
Endocrine
Subchronic
Rat, Sprague-
Inhalation,
0, 50, 300 or
6 hours/day.
NOAEL= 1800
No effects on
(Kim et al..
N/A
Dawley, M/F
whole body.
1800 ppm
5 days/ week
organ weights
1999a)
(n=20/group)
vapor
for 8 weeks
or histo-
pathology
Page 431 of 486
-------
Target
Organ/
System
Study Type
Species/
Strain/Sex
(Number/
group)1
Exposure
Route
Doses/
Concentrations2
Duration3
Effect Dose/
Concentration
(ppm or
mg/kg-day)4
(Sex)
Effect5
Reference6
Data Quality
Evaluation7'8
Endocrine
Subchronic
Rat, Wistar, M
Inlialation,
0, 200, 400 or
8 hours/day.
NOAEL= 800
No effects on
(Icliihara et
High
(n=8-9/group)
whole body,
vapor
800 ppm
7 days/ week
for 12 weeks
(M)
organ weights
or liisto-
pathology
al.. 2000a:
Icliihara et
al.. 2000b)
Endocrine
Subchronic
Rat, Wistar, F
Inlialation,
0, 200, 400 or
8 hours/day.
NOAEL= 800
No effects on
(Yamada et
High
(n=10/group)
whole body,
vapor
800 ppm
7 days/ week
for up to
12 weeks
(F)
organ weights
or liisto-
pathology
al.. 2003)
Endocrine
Chronic
Rat, Albino,
Inlialation,
0, 100, 200, 400
6 hours/day.
NOAEL= 600
No effects on
(ClinTrials.
High
MZF
whole body.
or 600 ppm
5 days/ week
organ weights
1997a)
(n=30/group)
vapor
for 13 weeks
or liisto-
pathology
Endocrine
Chronic
Rat, F344/N,
Inlialation,
0, 62.5, 125,
6.2 hours/day.
NOAEL= 1000
No effects on
(NTP.
High
M/F
whole body.
250, 500 or 1000
5 days/week
organ weights
2011a)
(n=20/group)
vapor
ppm
for 14 weeks
Endocrine
Chronic
Rat, F344/N,
Inlialation,
0, 125, 250 or
6.2 hours/day.
NOAEL= 500
No effects on
(NTP.
High
M/F
whole body.
500 ppm
5 days/week
liistopathology
2011a)
(n=100/group)
vapor
for 105 weeks
Endocrine
Repro-
Rat,
Inlialation,
0, 100, 250, 500
6 hours/day
NOAEL= 500
Decreased
(WIL
High
ductive/
Crl:CD(SD)IG
whole body.
or 750 ppm
during pre-
(M)
absolute
Research.
Develop-
S BR, M/F
vapor
mating
weights of
2001)
mental
(n=50
FO/group; 49-
50 F1
adults/group)
(>70 days),
throughout
mating, and
until sacrifice
in males; or
until GD 20
and from PND
5 until
weaning of
offspring
(~PND 21) in
females
adrenals and
pituitary (Fi)
Page 432 of 486
-------
Target
Organ/
System
Study Type
Species/
Strain/Sex
(Number/
group)1
Exposure
Route
Doses/
Concentrations2
Duration3
Effect Dose/
Concentration
(ppm or
mg/kg-day)4
(Sex)
Effect5
Reference6
Data Quality
Evaluation7'8
Endocrine
Chronic
Mouse,
Inlialation,
0, 62.5, 125 or
6.2 hours/day.
NOAEL= 250
Necrosis of
(NTP.
High
B6C3F1, M/F
whole body.
500 ppm
5 days/week
(F)
adrenal cortex
2011a)
(n=20/group)
vapor
for 14 weeks
(moderate to
marked)
Endocrine
Chronic
Mouse,
Inlialation,
0, 62.5, 125 or
6.2 hours/day.
NOAEL= 250
No effects on
(NTP.
High
B6C3F1, M/F
whole body.
500 ppm
5 days/week
liistopathology
2011a)
(n=100/group)
vapor
for 105 weeks
Gastro-
Chronic
Rat, Albino,
Inlialation,
0, 100, 200, 400
6 hours/day.
NOAEL= 600
No effects on
(ClinTrials.
High
intestinal
M/F
(n=30/group)
whole body,
vapor
or 600 ppm
5 days/ week
for 13 weeks
liistopathology
1997a)
Gastro-
Chronic
Rat, F344/N,
Inlialation,
0, 62.5, 125,
6.2 hours/day.
NOAEL= 1000
No effects on
(NTP.
High
intestinal
M/F
(n=20/group)
whole body,
vapor
250, 500 or 1000
ppm
5 days/week
for 14 weeks
liistopathology
2011a)
Gastro-
Chronic
Rat, F344/N,
Inlialation,
0, 125, 250 or
6.2 hours/day.
NOAEL= 500
No effects on
(NTP.
High
intestinal
M/F
(n=100/group)
whole body,
vapor
500 ppm
5 days/week
for 105 weeks
liistopathology
2011a)
Gastro-
Chronic
Mouse,
Inlialation,
0, 62.5, 125, 250
6.2 hours/day.
NOAEL= 500
No effects on
(NTP.
High
intestinal
B6C3F1, M/F
(n=20/group)
whole body,
vapor
or 500 ppm
5 days/week
for 14 weeks
liistopathology
2011a)
Gastro-
Chronic
Mouse,
Inlialation,
0, 62.5, 125 or
6.2 hours/day.
NOAEL= 250
No effects on
(NTP.
High
intestinal
B6C3F1, M/F
(n=100/group)
whole body,
vapor
250 ppm
5 days/week
for 105 weeks
liistopathology
2011a)
Hemato-
Acute
Rat, M
Inlialation
0, 6040, 7000,
4 hours
NOAEL= 8500
No effects on
(Elf
N/A
logical
(n=10/group)
7400 or 8500
ppm
(M)
hematology
parameters
Atochem.
1997)
Hemato-
Short-term
Rat
Inlialation
0, 398, 984 or
6 hours/day.
NOAEL= 398
Decreased
(ClinTrials.
N/A
logical
(n=20/group)
1590 ppm
5 days/ week
for 4 weeks
erythrocyte
parameters
1997b)
Hemato-
Subchronic
Rat, Wistar, M
Inlialation,
0 or 1000 ppm
8 hours/day.
LOAEL= 1000
Decreased
(Yu et al..
Medium
logical
(n=9/group)
whole body,
vapor
7 days/ week
for 5 or
7 weeks
(M)
mean
corpuscular
volume
2001)
Page 433 of 486
-------
Target
Organ/
System
Study Type
Species/
Strain/Sex
(Number/
group)1
Exposure
Route
Doses/
Concentrations2
Duration3
Effect Dose/
Concentration
(ppm or
mg/kg-day)4
(Sex)
Effect5
Reference6
Data Quality
Evaluation7'8
Hemato-
Subchronic
Rat, Sprague-
Inlialation,
0, 50, 300 or
6 hours/day.
NOAEL= 300
Decreased
(Kim et al..
N/A
logical
Dawley, M/F
(n=20/group)
whole body,
vapor
1800 ppm
5 days/ week
for 8 weeks
WBCs, RBCs,
hematocrit
and MCV;
increased Hgb
and MCH
1999a)
Hemato-
Subchronic
Rat, Wistar, M
Inlialation,
0, 200, 400 or
8 hours/day.
NOAEL= 400
Decreased
(Ichihara et
High
logical
(n=8-9/group)
whole body,
vapor
800 ppm
7 days/ week
for 12 weeks
(M)
MCHC;
increased
MCV
al.. 2000b)
Hemato-
Chronic
Rat, Albino,
Inlialation,
0, 100, 200, 400
6 hours/day.
NOAEL= 400
Decreased
(ClinTrials.
High
logical
M/F
(n=30/group)
whole body,
vapor
or 600 ppm
5 days/ week
for 13 weeks
(F)
WBCand
absolute
lymphocytes
(at 6 weeks)
1997a)
Hemato-
Chronic
Rat, F344/N,
Inlialation,
0, 62.5, 125,
6.2 hours/day.
NOAEL= 1000
No effects on
(NTP.
High
logical
M/F
(n=20/group)
whole body,
vapor
250, 500 or 1000
ppm
5 days/week
for 14 weeks
hematology
parameters
2011a)
Hemato-
Chronic
Mouse,
Inlialation,
0, 62.5, 125, 250
6.2 hours/day.
NOAEL= 500
No effects on
(NTP.
High
logical
B6C3F1, M/F
(n=20/group)
whole body,
vapor
or 500 ppm
5 days/week
for 14 weeks
hematology
parameters
2011a)
Immune
Short-term/
Rat, F344/N, F
Inlialation,
0, 250, 500 or
6.2 hours/day.
NOAEL= 500
Decreased
(Anderson et
Medium
Subchronic
(n=8/group)
whole body,
vapor
1000 ppm
5 days/week
for 4 or
10 weeks
(F)
spleen IgM
response to
SRBC;
decreased T
cells
al.. 2010)
Immune
Subchronic
Rat, Sprague-
Inlialation,
0, 50, 300 or
6 hours/day.
NOAEL= 1800
No effects on
(Kim et al..
N/A
Dawley, M/F
whole body.
1800 ppm
5 days/ week
liistopathology
1999a)
(n=20/group)
vapor
for 8 weeks
(thymus and
spleen)
Page 434 of 486
-------
Target
Organ/
System
Study Type
Species/
Strain/Sex
(Number/
group)1
Exposure
Route
Doses/
Concentrations2
Duration3
Effect Dose/
Concentration
(ppm or
mg/kg-day)4
(Sex)
Effect5
Reference6
Data Quality
Evaluation7'8
Immune
Subchronic
Rat, Wistar, M
Inlialation,
0, 200, 400 or
8 hours/day.
NOAEL= 800
No effects on
(Ichihara et
High
(n=8-9/group)
whole body,
vapor
800 ppm
7 days/ week
for 12 weeks
(M)
organ weights
or liisto-
pathology
(spleen and
thymus)
al.. 2000b)
Immune
Subchronic
Rat, Wistar, F
Inlialation,
0, 200, 400 or
8 hours/day.
NOAEL= 800
No effects or
(Yamada et
High
(n=10/group)
whole body,
vapor
800 ppm
7 days/ week
for up to
12 weeks
(F)
organ weights
or liisto-
pathology
(spleen and
thymus)
al.. 2003)
Immune
Chronic
Rat, Albino,
Inlialation,
0, 100, 200, 400
6 hours/day.
NOAEL= 600
No immune
(ClinTrials.
High
MZF
whole body.
or 600 ppm
5 days/ week
effects
1997a)
(n=30/group)
vapor
for 13 weeks
Immune
Chronic
Rat, F344/N,
Inlialation,
0, 62.5, 125,
6.2 hours/day.
NOAEL= 1000
No effects on
(NTP.
High
M/F
whole body.
250, 500 or 1000
5 days/week
liistopathology
2011a)
(n=20/group)
vapor
ppm
for 14 weeks
(lympho-
reticular
tissues)
Immune
Chronic
Rat, F344/N,
Inlialation,
0, 125, 250 or
6.2 hours/day.
NOAEL= 500
No effects on
(NTP.
High
M/F
whole body.
500 ppm
5 days/week
liistopathology
2011a)
(n=100/group)
vapor
for 105 weeks
(lympho-
reticular
tissues)
Page 435 of 486
-------
Target
Organ/
System
Study Type
Species/
Strain/Sex
(Number/
group)1
Exposure
Route
Doses/
Concentrations2
Duration3
Effect Dose/
Concentration
(ppm or
mg/kg-day)4
(Sex)
Effect5
Reference6
Data Quality
Evaluation7'8
Immune
Repro-
Rat,
Inlialation,
0, 100, 250, 500
6 hours/day
NOAEL= 750
Increased
(WIL
High
ductive/
Crl:CD(SD)IG
whole body.
or 750 ppm
during pre-
brown
Research.
Develop-
SBRM/F
vapor
mating
pigment in the
2001)
mental
(n=50 FO
/group; 49-50
F1
adults/group;
41-47 F1
weanlings/grou
p; 30-44 F2
weanlings/grou
P))
(>70 days),
throughout
mating, and
until sacrifice
in males; or
until GD 20
and from PND
5 until
weaning of
offspring
(~PND 21) in
females
spleen
Immune
Short-term/
Mouse,
Inlialation,
0, 125, 250 or
6.2 hours/day.
LOAEL= 125
Decreased
(Anderson et
Medium
Subchronic
B6C3F1, F
(n=5-8/group)
whole body,
vapor
500 ppm
5 days/week
for 4 or
10 weeks
(F)
spleen IgM
response to
SRBC
al.. 2010)
Immune
Chronic
Mouse,
Inlialation,
0, 62.5, 125, 250
6.2 hours/day.
NOAEL= 500
No effects on
(NTP.
High
B6C3F1, M/F
whole body.
or 500 ppm
5 days/week
liistopathology
2011a)
(n=20/group)
vapor
for 14 weeks
(lympho-
reticular
tissues)
Immune
Chronic
Mouse,
Inlialation,
0, 62.5, 125 or
6.2 hours/day.
NOAEL= 250
No effects on
(NTP.
High
B6C3F1, M/F
whole body.
250 ppm
5 days/week
liistopathology
2011a)
(n=100/group)
vapor
for 105 weeks
(lympho-
reticular
tissues)
Page 436 of 486
-------
Target
Organ/
System
Study Type
Species/
Strain/Sex
(Number/
group)1
Exposure
Route
Doses/
Concentrations2
Duration3
Effect Dose/
Concentration
(ppm or
mg/kg-day)4
(Sex)
Effect5
Reference6
Data Quality
Evaluation7'8
Immune
Acute
Mouse,
Oral,
0, 200, 500 or
Single
LOAEL= 200
Reduced
(Lee et al..
N/A
BALB/c, F
gavage
1000 mg/kg
exposure;
mg/kg (F)
antibody
2007)
(n=5/group)
(corn oil
vehicle)
necropsy after
6, 12, 24 or
48 hours
response to T-
antigen; used
for weight of
evidence; no
route-to-route
extrapolation
Hepatic
Short-term
Rat, F344/N,
Inhalation,
0, 125, 250, 500,
6.2 hours/day.
NOAEL= 125
Increased
(NTP.
High
MZF
whole body.
1000 or 2000
5 days/week
(M)
absolute and
2011a)
(n=10/group)
vapor
ppm
for 16 days
relative liver
weights
Hepatic
Subchronic
Rat, Wistar, M
Inhalation,
0 or 1000 ppm
8 hours/day.
LOAEL= 1000
No effects on
(Yu et al..
Medium
(n=9/group)
whole body,
vapor
7 days/week
for 5 or
7 weeks
(M)
histopathology
2001)
Hepatic
Subchronic
Rat, Sprague-
Inhalation,
0, 50, 300 or
6 hours/day.
NOAEL= 50
Increased
(Kim et al..
N/A
Dawley, M/F
whole body.
1800 ppm
5 days/week
(M)
relative liver
1999b)
(n=20/group)
vapor
for 8 weeks
weight
Hepatic
Subchronic
Rat, Wistar, M
Inhalation,
0, 700 or 1500
6 hours/day.
LOAEL= 700
Decreased
(Fueta et al..
N/A
(n=10/group)
whole body,
vapor
ppm
5 days/ week
for 4 and
12 weeks
(M)
plasma ALT
activity
2002b)
Hepatic
Subchronic
Rat, Wistar, M
Inhalation,
0, 200, 400 or
8 hours/day.
NOAEL= 400
Increased
(Ichihara et
High
(n=8-9/group)
whole body,
vapor
800 ppm
7 days/ week
for 12 weeks
(M)
absolute and
relative liver
weight
al.. 2000b)
Hepatic
Subchronic
Rat, Wistar, F
Inhalation,
0, 200, 400 or
8 hours/day.
LOAEL= 1016
Increased
(Yamada et
High
(n=10/group)
whole body,
vapor
800 ppm
7 days/ week
for up to
12 weeks
mg/m3 (F)
absolute and
relative liver
weight
al.. 2003)
Page 437 of 486
-------
Target
Organ/
System
Study Type
Species/
Strain/Sex
(Number/
group)1
Exposure
Route
Doses/
Concentrations2
Duration3
Effect Dose/
Concentration
(ppm or
mg/kg-day)4
(Sex)
Effect5
Reference6
Data Quality
Evaluation7'8
Hepatic
Chronic
Rat, Albino,
MZF
(n=30/group)
Inlialation,
whole body,
vapor
0, 100, 200, 400
or 600 ppm
6 hours/day,
5 days/ week
for 13 weeks
LOAEL= 100
(M)
Increased
incidence of
cytoplasmic
vacuolization
(ClinTrials.
1997a)
High
Hepatic
Chronic
Rat, F344/N,
MZF
(n=20/group)
Inlialation,
whole body,
vapor
0, 62.5, 125,
250, 500 or 1000
ppm
6.2 hours/day,
5 days/week
for 14 weeks
NOAEL= 125
(F)
Increased liver
weight;
increased
incidence of
cytoplasmic
vacuolization
(NTP,
2011a)
High
Hepatic
Chronic
Rat, F344/N,
MZF
(n=100/group)
Inlialation,
whole body,
vapor
0, 125, 250 or
500 ppm
6.2 hours/day,
5 days/week
for 105 weeks
NOAEL= 500
No effects on
liistopathology
(NTP,
2011a)
High
Hepatic
Repro-
ductive/
Develop-
mental
Rat,
Crl:CD(SD)IG
SBRM/F
(n=50
FO/group; 49-
50 F1
adults/group)
Inlialation,
whole body,
vapor
0, 100, 250, 500
or 750 ppm
6 hours/day
during pre-
mating
(>70 days),
throughout
mating, and
until sacrifice
NOAEL= 100
(M)
Increased
incidence of
vacuolization
of
centrilobular
hepatocytes
(Fo)
(WIL
Research.
2001)
High
Hepatic
Repro-
ductive/
Develop-
mental
Rat,
Crl:CD(SD)IG
SBRM/F
(n=50
FO/group; 49-
50 F1
adults/group)
Inlialation,
whole body,
vapor
0, 100, 250, 500
or 750 ppm
6 hours/day
during pre-
mating
(>70 days),
throughout
mating, and
until GD 20;
from PND 5
until weaning
of offspring
(-PND21)
NOAEL= 250
(F)
Increased
incidence of
vacuolization
of
centrilobular
hepatocytes
(Fo)
(WIL
Research.
2001)
High
Page 438 of 486
-------
Target
Organ/
System
Study Type
Species/
Strain/Sex
(Number/
group)1
Exposure
Route
Doses/
Concentrations2
Duration3
Effect Dose/
Concentration
(ppm or
mg/kg-day)4
(Sex)
Effect5
Reference6
Data Quality
Evaluation7'8
Hepatic
Short-term
Mouse,
B6C3F1, M/F
(n=10/group)
Inhalation,
whole body,
vapor
0, 125, 250, 500,
1000 or 2000
ppm
6.2 hours/day,
5 days/week
for 17 days
NOAEL= 250
(M)
Centrilobular
necrosis (mild
to moderate)
(NTP,
2011a)
High
Hepatic
Short-term
Mouse,
C57BL/6J,
DBA/2J and
BALB/cA,
M
(n=6/strain/gro
up)
Inhalation,
whole body,
vapor
0, 50, 110 or 250
ppm
8 hours/day,
7 days/ week
for 4 weeks
LOAEL= 50
(M)
Hepatocellular
degeneration
and focal
necrosis
(Liu et al..
2009)
High
Hepatic
Short-term
Mouse,
C57BL/6J
( Yr/2-null and
wild-type), M
(n=8/genotype/
group)
Inhalation,
whole body,
vapor
0, 100 or 300
ppm
8 hours/day,
7 days/ week
for 4 weeks
LOAEL= 100
(M)
Necrosis and
hepatocyte
degeneration
(Liu et al..
2010)
N/A
Hepatic
Chronic
Mouse,
B6C3F1, M/F
(n=20/group)
Inhalation,
whole body,
vapor
0, 62.5, 125, 250
or 500 ppm
6.2 hours/day,
5 days/week
for 14 weeks
NOAEL= 250
Necrosis and
hepatocyte
degeneration
(NTP,
2011a)
High
Hepatic
Chronic
Mouse,
B6C3F1, M/F
(n=100/group)
Inhalation,
whole body,
vapor
0, 62.5, 125 or
250 ppm
6.2 hours/day,
5 days/week
for 105 weeks
NOAEL= 250
No effects on
histopathology
(NTP,
2011a)
High
Hepatic
Chronic
Rat, M
(n=10/group)
Oral
0, 200, 400 or
800 mg/kg-day
16 weeks
LOAEL= 200
mg/kg-day (M)
Increased
relative liver
weight; used
for weight of
evidence; no
route-to-route
extrapolation
(Wans et al..
2012)
N/A
Page 439 of 486
-------
Target
Organ/
System
Study Type
Species/
Strain/Sex
(Number/
group)1
Exposure
Route
Doses/
Concentrations2
Duration3
Effect Dose/
Concentration
(ppm or
mg/kg-day)4
(Sex)
Effect5
Reference6
Data Quality
Evaluation7'8
Hepatic
Acute
Mouse,
BALB/c, F
(n=5/group)
Oral,
gavage
(corn oil
vehicle)
0, 200, 500 or
1000 mg/kg
Single
exposure;
necropsy after
6, 12, 24 or
48 hours
NOAEL= 200
mg/kg (F)
Centrilobular
hepatocyte
swelling
(Lee et al..
2007)
N/A
Metabolic
Chronic
Rat, Albino,
MZF
(n=30/group)
Inhalation,
whole body,
vapor
0, 100, 200, 400
or 600 ppm
6 hours/day,
5 days/ week
for 13 weeks
NOAEL= 600
No effects on
electrolyte or
glucose levels
(ClinTrials.
1997a)
High
Musculo-
skeletal
Subchronic
Rat, Wistar, M
(n=2/group)
Inhalation,
whole body,
vapor
0, 200, 400 or
800 ppm
8 hours/day,
7 days/ week
for 12 weeks
NOAEL= 400
(M)
Alteration in
soleus muscle
myofilaments
(Ichihara et
al.. 2000a)
High
Musculo-
skeletal
Chronic
Rat, Albino,
MZF
(n=30/group)
Inhalation,
whole body,
vapor
0, 100, 200, 400
or 600 ppm
6 hours/day,
5 days/ week
for 13 weeks
NOAEL= 600
No effects on
histopathology
(ClinTrials.
1997a)
High
Musculo-
skeletal
Chronic
Rat, F344/N,
MZF
(n=20/group)
Inhalation,
whole body,
vapor
0, 62.5, 125,
250, 500 or 1000
ppm
6.2 hours/day,
5 days/week
for 14 weeks
NOAEL= 1000
No effects on
histopathology
(NTP,
2011a)
High
Musculo-
skeletal
Chronic
Rat, F344/N,
MZF
(n=100/group)
Inhalation,
whole body,
vapor
0, 125, 250 or
500 ppm
6.2 hours/day,
5 days/week
for 105 weeks
NOAEL= 500
No effects on
histopathology
(NTP,
2011a)
High
Musculo-
skeletal
Chronic
Mouse,
B6C3F1, M/F
(n=20/group)
Inhalation,
whole body,
vapor
0, 62.5, 125, 250
or 500 ppm
6.2 hours/day,
5 days/week
for 14 weeks
NOAEL= 500
No effects on
histopathology
(NTP,
2011a)
High
Musculo-
skeletal
Chronic
Mouse,
B6C3F1, M/F
(n=100/group)
Inhalation,
whole body,
vapor
0, 62.5, 125 or
250 ppm
6.2 hours/day,
5 days/week
for 105 weeks
NOAEL= 250
No effects on
histopathology
(NTP,
2011a)
High
Neurological
Subchronic
Rat, Sprague-
Dawley, M/F
(n=20/group)
Inhalation,
whole body,
vapor
0, 50, 300 or
1800 ppm
6 hours/day,
5 days/ week
for 8 weeks
NOAEL= 50
(M)
Decreased
relative brain
weight
(Kim et al..
1999a)
N/A
Page 440 of 486
-------
Target
Organ/
System
Study Type
Species/
Strain/Sex
(Number/
group)1
Exposure
Route
Doses/
Concentrations2
Duration3
Effect Dose/
Concentration
(ppm or
mg/kg-day)4
(Sex)
Effect5
Reference6
Data Quality
Evaluation7'8
Neurological
Acute
Rat, Sprague-
Inhalation,
0, 11,000,
4 hours
LOAEL=
Ataxia,
(Kim et al..
N/A
Dawley, M/F
whole body.
13,000, 15,000
11,000
lacrimation.
1999a)
(n=10/group)
vapor
or 17,000 ppm
decreased
activity
Neurological
Short-term
Rat, Wistar, M
Inhalation,
0, 200, 400 or
8 hours/day for
LOAEL= 200
Altered
(Wans et al..
N/A
(n=9/group)
whole body,
vapor
800 ppm
7 days
(M)
neuron-
specific
proteins and
ROS
2002)
Neurological
Short-term
Rat, Wistar, M
Inhalation,
0, 200, 400, 800
8 hours/day for
LOAEL= 200
Decreased
(Zhane et
High
(n=12/group)
whole body,
vapor
or 1000 ppm
7 or 28 days
(M)
hippocampal
glucocorticoid
receptor
expression
al.. 2013)
Neurological
Short-term
Rat, Wistar, M
Inhalation,
0 or 1500 ppm
6 hours/day.
LOAEL= 1500
Paired pulse
(Fueta et al..
N/A
(n=6-13/
whole body.
5 days/ week
(M)
disinhibition
2002a; Fueta
exposure
vapor
for 1, 3 or
(DG and CA1
et al.. 2002b)
group; n=6-
4 weeks
pyramidal
10/control
neuron);
group)
neuronal
dysfunction in
dentate gyrus;
convulsive
behaviors
Neurological
Short-term
Rat, F344, M
Inhalation,
0, 400 or 1000
8 hours/day.
LOAEL= 400
Altered
(Huans et
N/A
(n=9/group)
whole body,
vapor
ppm
7 days/ week
for 1 or
4 weeks
(M)
regulation and
expression of
hippocampal
proteins
al.. 2011)
Neurological
Short-term
Rat, F344, M
Inhalation,
0, 400 or 1000
8 hours/day.
LOAEL= 400
Increased
(Huans et
N/A
(n=9/group)
whole body,
vapor
ppm
7 days/ week
for 1 or
4 weeks
(M)
hippocampal
ROS levels
al.. 2012)
Page 441 of 486
-------
Target
Organ/
System
Study Type
Species/
Strain/Sex
(Number/
group)1
Exposure
Route
Doses/
Concentrations2
Duration3
Effect Dose/
Concentration
(ppm or
mg/kg-day)4
(Sex)
Effect5
Reference6
Data Quality
Evaluation7'8
Neurological
Short-term
Rat F344, M
Inhalation,
0, 400 or 1000
8 hours/day.
LOAEL= 400
Altered
(Hnana et
N/A
(n=9/group)
whole body,
vapor
ppm
7 days/ week
for 1 or
4 weeks
(M)
regulation and
expression of
liippocampal
proteins
al.. 2015)
Neurological
Short-term
Rat F344, M
Inlialation,
0, 10, 50 or 200
8 hours/day.
NOAEL= 10
Increased
(Honma et
High
(n=2/group)
whole body,
vapor
ppm
7 days/week
for 3 weeks
(M)
spontaneous
locomotor
activity
al.. 2003)
Neurological
Short-term
Rat F344, M
Inlialation,
0, 10, 50, 200 or
8 hours/day.
NOAEL= 50
Decreased
(Honma et
High
(n=5/group)
whole body,
vapor
1000 ppm
7 days/ week
for 3 weeks
(M)
time hanging
from a
suspended bar
al.. 2003)
Neurological
Short-term
Rat F344, M
Inlialation,
0, 50, 200 or
8 hours/day.
LOAEL= 50
Altered neuro-
(Suda et al..
N/A
(n=4-5/group)
whole body,
vapor
1000 ppm
7 days/ week
for 3 weeks
(M)
transmitter
and
metabolites
2008)
Neurological
Short-term
Rat
(n=20/group)
Inlialation
0, 398, 994 or
1590 ppm
6 hours/day,
5 days/ week
for 4 weeks
LOAEL= 398
Histo-
pathological
abnormalities
in the CNS
(ClinTrials.
1997b)
N/A
Neurological
Short-term
Rat F344, M
Inlialation,
0, 400 or 1000
8 hours/day.
NOAEL= 400
Changes in the
(Mohideen
N/A
(n=9/group)
whole body,
vapor
ppm
7 days/ week
for 4 weeks
(M)
mRNA
expression of
serotonin,
dopamine, and
GABA
receptors
et al.. 2009)
Page 442 of 486
-------
Target
Organ/
System
Study Type
Species/
Strain/Sex
(Number/
group)1
Exposure
Route
Doses/
Concentrations2
Duration3
Effect Dose/
Concentration
(ppm or
mg/kg-day)4
(Sex)
Effect5
Reference6
Data Quality
Evaluation7'8
Neurological
Short-term
Rat F344, M
Inlialation,
0, 400 or 1000
8 hours/day.
NOAEL= 400
Decreased
(Moliideen
N/A
(n=6/group)
whole body,
vapor
ppm
7 days/ week
for 4 weeks
(M)
density of
noradrenergic
axons in
frontal cortex
and amygdala
etal.,2011)
Neurological
Short-term
Rat F344, M
Inlialation,
0, 400 or 1000
8 hours/day.
LOAEL= 400
Increased
(Moliideen
High
(n=12/group)
whole body,
vapor
ppm
7 days/week
for 4 weeks
(M)
astrogliosis
etal.,2013)
Neurological
Short-term
Rat, Wistar-ST,
Inlialation,
0, 400, 800 or
8 hours/day.
LOAEL= 400
Morphological
(Subramania
N/A
M
whole body.
1000 ppm
7 days/ week
(M)
changes in
n et al..
(n=12/group)
vapor
for 4 weeks
cerebellar
microglia and
increased
ROS
2012)
Neurological
Short-term
Rat, M
Inlialation,
0 or 1500 ppm
6 hours/day.
LOAEL= 1500
Decreased
(Ohnishi et
N/A
(n=8/group)
whole body
5 days/ week
for 4 weeks
(M)
activity,
behavioral
abnormalities,
movement
disorders,
liisto-
pathological
changes in
Purkinje cells
al.. 1999)
Neurological
Short-term/
Rat, Wistar, M
Inlialation,
0 or 700pm
6 hours/day.
LOAEL= 700
Paired pulse
(Fueta et al..
N/A
Subchronic
(n=7-14/group)
whole body,
vapor
5 days/week
for 4, 8 or
12 weeks
(M)
disinliibition
in ex vivo
liippocampal
slices (DG and
CA1
pyramidal
neuron)
2004)
Page 443 of 486
-------
Target
Organ/
System
Study Type
Species/
Strain/Sex
(Number/
group)1
Exposure
Route
Doses/
Concentrations2
Duration3
Effect Dose/
Concentration
(ppm or
mg/kg-day)4
(Sex)
Effect5
Reference6
Data Quality
Evaluation7'8
Neurological
Subchronic
Rat, Wistar, M
(n=9/group)
Inhalation,
whole body,
vapor
0 or 1000 ppm
8 hours/day,
7 days/ week
for 5 or
7 weeks
LOAEL= 1000
(M)
Movement
disorder,
altered motor
nerve
conduction
velocity and
distal nerve
latency in tail
nerve); liisto-
pathological
changes to
CNS and PNS
(Yu et al..
2001)
Medium
Neurological
Subchronic
Rat, Wistar, M
(n=24/group)
Inhalation,
whole body,
vapor
0, 400, 800 or
1000 ppm
8 hours/day,
7 days/ week
for 6 weeks
NOAEL= 400
(M)
Movement
disorder,
decreased
hind limb grip
strength
(Banu et al..
2007)
N/A
Neurological
Subchronic
Rat, Wistar M
(n=12/group)
Inhalation,
whole body,
vapor
0 or 700 ppm
6 hours/day,
5 days/ week
for 8 weeks
LOAEL= 700
(M)
Paired pulse
disinhibition
in ex vivo
hippocampal
slices (DG and
CA1
pyramidal
neuron);
increased
protein kinase
activities
(Fucta et al..
2002a)
N/A
Page 444 of 486
-------
Target
Organ/
System
Study Type
Species/
Strain/Sex
(Number/
group)1
Exposure
Route
Doses/
Concentrations2
Duration3
Effect Dose/
Concentration
(ppm or
mg/kg-day)4
(Sex)
Effect5
Reference6
Data Quality
Evaluation7'8
Neurological
Subchronic
Rat, Wistar, M
Inhalation,
0, 200 or 400
6 hours/day.
NOAEL= 200
Paired pulse
(Fueta et al..
Medium
(n=6/group)
whole body,
vapor
ppm
5 days/ week
for 8 or
12 weeks
(M)
disinhibition
in ex vivo
hippocampal
slices (DG and
CA1
pyramidal
neuron)
2007)
Neurological
Subchronic
Rat, Sprague-
Inhalation,
0, 50, 300 or
6 hours/day.
NOAEL= 1800
No effects on
(Kim et al..
N/A
Dawley, M/F
whole body.
1800 ppm
5 days/ week
brain liisto-
1999a)
(n=20/group)
vapor
for 8 weeks
pathology
Neurological
Subchronic
Rat, Wistar, M
Inhalation,
0, 200, 400 or
8 hours/day.
LOAEL= 200
Decreased
(Ichihara et
High
(n=8-9/group)
whole body,
vapor
800 ppm
7 days/ week
for 12 weeks
(M)
hind limb grip
strength
al.. 2000a)
Neurological
Subchronic
Rat, Wistar, M
Inhalation,
0, 200, 400 or
8 hours/day.
LOAEL= 200
Altered
(Wans et al..
N/A
(n=9/group)
whole body,
vapor
800 ppm
7 days/ week
for 12 weeks
(M)
neuron-
specific
proteins and
increased
ROS
2003)
Neurological
Subchronic
Rat, Wistar, M
Inhalation,
0 or 400 ppm
6 hours/day.
LOAEL= 400
Changes in
(Yoshida et
N/A
(n=6/group)
whole body,
vapor
5 days/ week
for 12 weeks
(M)
gene
expression of
anti-apoptotic
proteins in
astrocytes
al.. 2007)
Neurological
Subchronic
Rat, Wistar, M
Inhalation,
0 or 400 ppm
6 hours/day.
LOAEL= 400
Decreased
(Ueno et al..
N/A
(n=8/group)
whole body,
vapor
5 days/ week
for 12 weeks
(M)
paired pulse
inhibition in
ex vivo
hippocampal
slices (dentate
gyrus)
2007)
Page 445 of 486
-------
Target
Organ/
System
Study Type
Species/
Strain/Sex
(Number/
group)1
Exposure
Route
Doses/
Concentrations2
Duration3
Effect Dose/
Concentration
(ppm or
mg/kg-day)4
(Sex)
Effect5
Reference6
Data Quality
Evaluation7'8
Neurological
Chronic
Rat, Albino,
MZF
(n=30/group)
Inlialation,
whole body,
vapor
0, 100, 200, 400
or 600 ppm
6 hours/day,
5 days/ week
for 13 weeks
NOAEL= 600
No changes
based on
functional
observational
battery, motor
activity, organ
weight, or
liistopathology
(ClinTrials.
1997a)
High
Neurological
Chronic
Rat, Sprague-
Dawley, M/F
(n=20/group)
Inlialation,
whole body,
vapor
0, 200, 500 or
1250 ppm
6 hours/day,
5 days/week
for 13 weeks
NOAEL= 1250
No effects
liistopathology
of central or
peripheral
nervous
tissues
(Sohnet al..
2002)
N/A
Neurological
Short-term
Rat, F344/N,
M/F
(n=10/group)
Inlialation,
whole body,
vapor
0, 125, 250, 500,
1000 or 2000
ppm
6.2 hours/day,
5 days/week
for 16 days
NOAEL= 1000
Hindlimb
splay
(NTP,
2011a)
High
Neurological
Chronic
Rat, F344/N,
M/F
(n=20/group)
Inlialation,
whole body,
vapor
0, 62.5, 125,
250, 500 or 1000
ppm
6.2 hours/day,
5 days/week
for 14 weeks
NOAEL= 1000
No effects
(NTP,
2011a)
High
Neurological
Chronic
Rat, F344/N,
M/F
(n=100/group)
Inlialation,
whole body,
vapor
0, 125, 250 or
500 ppm
6.2 hours/day,
5 days/week
for 105 weeks
NOAEL= 500
No effects
(NTP,
2011a)
High
Page 446 of 486
-------
Species/
Strain/Sex
(Number/
group)1
Effect Dose/
Target
Organ/
System
Study Type
Exposure
Route
Doses/
Concentrations2
Duration3
Concentration
(ppm or
mg/kg-day)4
(Sex)
Effect5
Reference6
Data Quality
Evaluation7'8
Neurological
Repro-
Rat,
Inhalation,
0, 100, 250, 500
6 hours/day
NOAEL= 100
Decreased
(WIL
High
ductive/
Crl:CD(SD)IG
whole body.
or 750 ppm
during pre-
brain weight
Research.
Develop-
SBRM/F
vapor
mating
(Fo)
2001)
mental
(n=50 FO
/group; 49-50
F1
adults/group;
41-47 F1
weanlings/grou
p; 30-44 F2
weanlings/grou
P)
(>70 days),
throughout
mating, and
until sacrifice
in males; or
until GD 20
and from PND
5 until
weaning of
offspring
(~PND 21) in
females
Neurological
Repro-
Rat,
Inhalation,
0, 100, 250, 500
6 hours/day
LOAEL= 100
Decreased
(WIL
High
ductive/
Crl:CD(SD)IG
whole body.
or 750 ppm
during pre-
(M)
brain weight
Research.
Develop-
SBRM/F
vapor
mating
(weanling and
2001)
mental
(n=50/group/
generation)
(>70 days),
throughout
mating, and
until sacrifice
in males; or
until GD 20
and from PND
5 until
weaning of
offspring
(~PND 21) in
females
adult Fi)
Page 447 of 486
-------
Target
Organ/
System
Study Type
Species/
Strain/Sex
(Number/
group)1
Exposure
Route
Doses/
Concentrations2
Duration3
Effect Dose/
Concentration
(ppm or
mg/kg-day)4
(Sex)
Effect5
Reference6
Data Quality
Evaluation7'8
Neurological
Repro-
Rat,
Inlialation,
0, 100, 250, 500
6 hours/day
NOAEL= 250
Decreased
(WIL
High
ductive/
Crl:CD(SD)IG
whole body.
or 750 ppm
during pre-
brain weight
Research.
Develop-
SBRM/F
vapor
mating
(weanling F2)
2001)
mental
(n=50 FO
/group; 49-50
F1
adults/group;
41-47 F1
weanlings/grou
p; 30-44 F2
weanlings/grou
P)
(>70 days),
throughout
mating, and
until sacrifice
in males; or
until GD 20
and from PND
5 until
weaning of
offspring
(~PND 21) in
females
Neurological
Short-term
Mouse,
B6C3F1, M/F
(n=10/group)
Inlialation,
whole body,
vapor
0, 125, 250, 500,
1000 or 2000
ppm
6.1 hours/day,
5 days/week
for 17 days
NOAEL= 2000
No effects
(NTP,
2011a)
High
Neurological
Chronic
Mouse,
B6C3F1, M/F
(n=20/group)
Inlialation,
whole body,
vapor
0, 62.5, 250,
500, 1000 or
2000 ppm
6.2 hours/day,
5 days/week
for 14 weeks
NOAEL= 500
No effects
(NTP,
2011a)
High
Neurological
Chronic
Mouse,
B6C3F1, M/F
(n=100/group)
Inlialation,
whole body,
vapor
0, 62.5, 125 or
250 ppm
6.2 hours/day,
5 days/week
for 105 weeks
NOAEL= 250
No effects
(NTP,
2011a)
High
Page 448 of 486
-------
Target
Organ/
System
Study Type
Species/
Strain/Sex
(Number/
group)1
Exposure
Route
Doses/
Concentrations2
Duration3
Effect Dose/
Concentration
(ppm or
mg/kg-day)4
(Sex)
Effect5
Reference6
Data Quality
Evaluation7'8
Neurological
Short-term
Rat, Wistar, M
(n=14/group)
Oral,
gavage
0, 100, 200,
400 or
800 mg/kg-day
12 days
1 .OAF.I ,= 100
mg/kg-day (M)
Impaired
spatial
learning and
memory;
neuron loss in
prelimbic
cortex;
increased
ROS in
cerebral
cortex
(Guo et al..
2015)
High
Neurological
Short-term
Rat, Wistar, M
(n=10/group)
Oral,
gavage
(corn oil
vehicle)
0, 200, 400 or
800 mg/kg-day
12 days
LOAEL= 200
mg/kg-day (M)
Impaired
spatial
learning and
memory. Used
for weight of
evidence
(Zhone et
al.. 2013)
Low
Neurological
Chronic
Rat, M
(n=10/group)
Oral
0, 200, 400 or
800 mg/kg-day
16 weeks
LOAEL= 200
mg/kg-day (M)
Decreased
hindlimb grip
strength;
increased gait
score; used for
weight of
evidence; no
route-to-route
extrapolation
(Wans et al..
2012)
N/A
Neurological
Short-term
Rat, Wistar, M
(n=7-9/group)
Sub-
cutaneous
0, 3.7 or
11 mmol/kg-day
4 weeks
1 .OAF.I .= 3.7
mmol/kg-day
(M)
Increased tail
motor nerve
latency
(Zhao et al..
1999)
N/A
Ocular
Chronic
Rat, Albino,
MZF
(n=30/group)
Inhalation,
whole body,
vapor
0, 100, 200, 400
or 600 ppm
6 hours/day,
5 days/ week
for 13 weeks
NOAEL= 600
No effects on
histopathology
(ClinTrials.
1997a)
High
Page 449 of 486
-------
Target
Organ/
System
Study Type
Species/
Strain/Sex
(Number/
group)1
Exposure
Route
Doses/
Concentrations2
Duration3
Effect Dose/
Concentration
(ppm or
mg/kg-day)4
(Sex)
Effect5
Reference6
Data Quality
Evaluation7'8
Ocular
Chronic
Rat, F344/N,
Inhalation,
0, 62.5, 125,
6.2 hours/day.
NOAEL= 1000
No effects on
(NTP.
High
MZF
whole body.
250, 500 or 1000
5 days/week
histopathology
2011a)
(n=20/group)
vapor
ppm
for 14 weeks
Ocular
Chronic
Rat, F344/N,
Inhalation,
0, 125, 250 or
6.2 hours/day.
NOAEL= 500
No effects on
(NTP.
High
M/F
whole body.
500 ppm
5 days/week
histopathology
2011a)
(n=100/group)
vapor
for 105 weeks
Ocular
Chronic
Mouse,
Inhalation,
0, 62.5, 125, 250
6.2 hours/day.
NOAEL= 500
No effects on
(NTP.
High
B6C3F1, M/F
whole body.
or 500 ppm
5 days/week
histopathology
2011a)
(n=20/group)
vapor
for 14 weeks
Ocular
Chronic
Mouse,
Inhalation,
0, 62.5, 125 or
6.2 hours/day.
NOAEL= 250
No effects on
(NTP.
High
B6C3F1, M/F
whole body.
250 ppm
5 days/week
histopathology
2011a)
(n=100/group)
vapor
for 105 weeks
Renal
Short-term
Rat, F344/N,
Inhalation,
0, 125, 250, 500,
6.2 hours/day.
LOAEL= 125
Increased
(NTP.
High
M/F
whole body.
1000 or 2000
5 days/week
(F)
relative
2011a)
(n=10/group)
vapor
ppm
for 16 days
kidney weight
Renal
Short-term
Rat
(n=20/group)
Inhalation
0, 398, 994 or
1590 ppm
6 hours/day,
5 days/ week
for 4 weeks
NOAEL= 398
Changes in
BUN, total
bilirubin, and
total protein
levels
(ClinTrials.
1997b)
N/A
Renal
Subchronic
Rat, Wistar, M
Inhalation,
0 or 1000 ppm
8 hours/day.
NOAEL= 1000
No effects on
(Yu et al..
Medium
(n=9/group)
whole body,
vapor
7 days/week
for 5 or
7 weeks
(M)
histopathology
2001)
Renal
Subchronic
Rat, Sprague-
Inhalation,
0, 50 to 1800
6 hours/day.
NOAEL= 300
Decreased
(Kim et al..
N/A
Dawley, M/F
whole body.
ppm
5 days/ week
urobilinogen
1999a)
(n=20/group)
vapor
for 8 weeks
(males);
increased
bilirubin
(females)
Page 450 of 486
-------
Target
Organ/
System
Study Type
Species/
Strain/Sex
(Number/
group)1
Exposure
Route
Doses/
Concentrations2
Duration3
Effect Dose/
Concentration
(ppm or
mg/kg-day)4
(Sex)
Effect5
Reference6
Data Quality
Evaluation7'8
Renal
Repro-
Rat, Wistar, M
Inlialation,
0, 200, 400 or
8 hours/day.
NOAEL= 800
No effects on
(Ichihara et
High
ductive
(n=8-9/group)
whole body,
vapor
800 ppm
7 days/ week
for 12 weeks
(M)
kidney weight
or liisto-
pathology
al.. 2000b)
Renal
Repro-
Rat, Wistar, F
Inlialation,
0, 200, 400 or
8 hours/day.
LOAEL= 200
Increased
(Yamada et
High
ductive
(n=10/group)
whole body,
vapor
800 ppm
7 days/ week
for up to
12 weeks
(F)
absolute and
relative
kidney weight
al.. 2003)
Renal
Chronic
Rat, Albino,
Inlialation,
0, 100, 200, 400
6 hours/day.
NOAEL= 600
No effects on
(ClinTrials.
High
MZF
whole body.
or 600 ppm
5 days/ week
(M)
urinalysis
1997a)
(n=30/group)
vapor
for 13 weeks
parameters, or
organ weights
Renal
Chronic
Rat, F344/N,
Inlialation,
0, 62.5, 125,
6.2 hours/day.
NOAEL= 500
Increased
(NTP.
High
MZF
whole body.
250, 500 or 1000
5 days/week
(F)
absolute and
2011a)
(n=20/group)
vapor
ppm
for 14 weeks
relative
kidney
weights
Renal
Chronic
Rat, F344/N,
Inlialation,
0, 125, 250 or
6.2 hours/day.
NOAEL= 500
No effects on
(NTP.
High
MZF
whole body.
500 ppm
5 days/week
liistopathology
2011a)
(n=100/group)
vapor
for 105 weeks
Renal
Repro-
Rat,
Inlialation,
0, 100 to 750
6 hours/day
NOAEL = 100
Increased
(WIL
High
ductive/
Crl:CD(SD)IG
whole body.
ppm
during pre-
(M)
incidence of
Research.
Develop-
SBRM/F
vapor
mating
pelvic
2001)
mental
(n=50 FO
/group; 49-50
F1
adults/group)
(>70 days),
throughout
mating, and
until sacrifice
mineralization
(Fo)
Page 451 of 486
-------
Target
Organ/
System
Study Type
Species/
Strain/Sex
(Number/
group)1
Exposure
Route
Doses/
Concentrations2
Duration3
Effect Dose/
Concentration
(ppm or
mg/kg-day)4
(Sex)
Effect5
Reference6
Data Quality
Evaluation7'8
Renal
Repro-
Rat,
Inhalation,
0, 100, 250, 500
6 hours/day
NOAEL = 100
Increased
(WIL
High
ductive/
Crl:CD(SD)IG
whole body.
or 750 ppm
during pre-
(F)
incidence of
Research.
Develop-
SBRM/F
vapor
mating
pelvic
2001)
mental
(n=50 FO
/group; 49-50
F1
adults/group)
(>70 days),
throughout
mating, and
until GD 20;
from PND 5
until weaning
of offspring
(-PND21)
mineralization
(Fo)
Renal
Short-term
Rat, F344/N,
Inhalation,
0, 125, 250, 500,
6.2 hours/day.
NOAEL= 500
Increased
(NTP.
High
M/F
whole body.
1000 or 2000
5 days/week
(F)
absolute and
2011a)
(n=10/group)
vapor
ppm
for 17 days
relative
kidney
weights
Renal
Chronic
Rat, F344/N,
Inhalation,
0, 62.5, 125, 250
6.2 hours/day.
NOAEL= 250
Increased
(NTP.
High
M/F
whole body.
or 500 ppm
5 days/week
(F)
absolute and
2011a)
(n=20/group)
vapor
for 14 weeks
relative
kidney
weights
Renal
Chronic
Mouse,
Inhalation,
0, 62.5, 125
6.2 hours/day.
NOAEL= 350
No effects on
(NTP.
High
B6C3F1, M/F
whole body.
or 250 ppm
5 days/week
histopathology
2011a)
(n=100/group)
vapor
for 105 weeks
Reproductive
Acute
Rat, M
(n=5/group)
Inhalation
0, 6040, 7000,
7400 or 8500
ppm
4 hours
NOAEL= 8500
(M)
No effects on
histopathology
of the testes
(Elf
Atochem.
1997)
N/A
Page 452 of 486
-------
Target
Organ/
System
Study Type
Species/
Strain/Sex
(Number/
group)1
Exposure
Route
Doses/
Concentrations2
Duration3
Effect Dose/
Concentration
(ppm or
mg/kg-day)4
(Sex)
Effect5
Reference6
Data Quality
Evaluation7'8
Reproductive
Acute
Rats, M
Oral
0, 400
lx daily /for 5
LOAEL= 400
Increased
Saito-Suzuki
N/A
Dominant
(n=15/group)
mg/kg/day
days; followed
(M)
implantation
et al.. 1982
Lethal
by mating for
loss at week 8;
Assay
8 consecutive
weeks
no increase in
dominant
mutation
index
Reproductive
Short-term
Rat F344, F
Inlialation,
50, 200 or
8 hours/day.
NOAEL= 1000
No effects on
(Sekieuchi
N/A
(n=7-8/group)
whole body,
vapor
1000 ppm
7 days/ week
for 3 weeks
(F)
number of
days per
estrous cycle
or ovary and
uterus weights
et al.. 2002)
Reproductive
Short-term
Rat, M
Inlialation
0, 398, 994 or
6 hours/day.
NOAEL= 1000
Microscopic
f CI inT rials.
N/A
(n=10/group)
1590 ppm
5 days/ week
for 4 weeks
(M)
lesions in
male
reproductive
system
1997b)
Reproductive
Subchronic
Rat, Wistar, M
Inlialation,
400, 800 or
8 hours/day.
LOAEL= 400
Decreased
(Banu et al..
N/A
(n=24/group)
whole body,
vapor
1000 ppm
7 days/ week
for 6 weeks
(M)
epididymal
sperm count
2007)
Reproductive
Subchronic
Rat, Wistar, M
Inlialation,
0 or 1000 ppm
8 hours/day.
NOAEL= 1000
No effects on
(Yu et al..
Medium
(n=9/group)
whole body,
vapor
7 days/ week
for 5 or
7 weeks
(M)
testis liisto-
pathology
2001)
Reproductive
Repro-
Rat, Wistar, F
Inlialation,
0, 200, 400
8 hours/day.
LOAEL= 200
Decreased
(Yamada et
High
ductive
(n=10/group)
whole body,
vapor
or 800 ppm
7 days/ week
for up to
12 weeks
(F)
number of
antral follicles
al.. 2003)
Reproductive
Subchronic
Rat, Sprague-
Dawley, M/F
(n=20/group)
Inlialation,
whole body,
vapor
50-1800 ppm
6 hours/day,
5 days/ week
for 8 weeks
NOAEL= 300
Increased
relative ovary
weight
(Kim et al..
1999a)
N/A
Page 453 of 486
-------
Target
Organ/
System
Study Type
Species/
Strain/Sex
(Number/
group)1
Exposure
Route
Doses/
Concentrations2
Duration3
Effect Dose/
Concentration
(ppm or
mg/kg-day)4
(Sex)
Effect5
Reference6
Data Quality
Evaluation7'8
Reproductive
Repro-
ductive
Rat, Wistar, M
(n=8-9/group)
Inlialation,
whole body,
vapor
0, 200, 400 or
800 ppm
8 hours/day,
7 days/ week
for 12 weeks
LOAEL = 200
(M)
Decreased
relative
seminal
vesicle weight
(Ichihara et
al.. 2000b)
High
Reproductive
Chronic
Rat, Albino,
MZF
(n=30/group)
Inlialation,
whole body,
vapor
0, 100, 200, 400
or 600 ppm
6 hours/day,
5 days/ week
for 13 weeks
NOAEL= 600
No effects on
organ weights
(ClinTrials.
1997a)
High
Reproductive
Chronic
Rat, F344/N,
MZF
(n=20/group)
Inlialation,
whole body,
vapor
0, 62.5, 125,
250, 500 or 1000
ppm
6.2 hours/day,
5 days/week
for 14 weeks
LOAEL= 250
(M)
Decreased
sperm motility
(NTP,
2011a)
High
Reproductive
Chronic
Rat, F344/N,
MZF
(n=20/group)
Inlialation,
whole body,
vapor
0, 62.5, 125,
250, 500 or 1000
ppm
6.2 hours/day,
5 days/week
for 14 weeks
LOAEL= 250
(F)
Alterations in
estrous cycles
(NTP,
2011a)
High
Reproductive
Chronic
Rat, F344/N,
MZF
(n=100/group)
Inlialation,
whole body,
vapor
0, 125, 250 or
500 ppm
6.2 hours/day,
5 days/week
for 105 weeks
NOAEL= 500
No effects on
liistopathology
of
reproductive
organs
(NTP,
2011a)
High
Reproductive
Repro-
ductive/
Develop-
mental
Rat,
Crl:CD(SD)IG
SBRM/F
(n=50 FO
/group; 49-50
F1
adults/group)
Inlialation,
whole body,
vapor
0, 100, 250, 500
or 750 ppm
6 hours/day
during pre-
mating
(>70 days),
throughout
mating, and
until sacrifice
NOAEL= 250
(M)
Decreased
percent motile
sperm (F0)
(WIL
Research.
2001)
High
Page 454 of 486
-------
Target
Organ/
System
Study Type
Species/
Strain/Sex
(Number/
group)1
Exposure
Route
Doses/
Concentrations2
Duration3
Effect Dose/
Concentration
(ppm or
mg/kg-day)4
(Sex)
Effect5
Reference6
Data Quality
Evaluation7'8
Reproductive
Repro-
ductive/
Develop-
mental
Rat,
Crl:CD(SD)IG
SBRM/F
(n=50 FO
/group; 49-50
F1
adults/group)
Inlialation,
whole body,
vapor
0, 100, 250, 500
or 750 ppm
6 hours/day
during pre-
mating
(>70 days),
throughout
mating, and
until sacrifice
NOAEL= 250
(M)
Decreased
percent
normal sperm
morphology
(Fo)
(WIL
Research.
2001)
High
Reproductive
Repro-
ductive/
Develop-
mental
Rat,
Crl:CD(SD)IG
SBRM/F
(n=50 FO
/group; 49-50
F1
adults/group)
Inlialation,
whole body,
vapor
0, 100, 250, 500
or 750 ppm
6 hours/day
during pre-
mating
(>70 days),
throughout
mating, and
until sacrifice
NOAEL= 100
(M)
Decreased
absolute
prostate
weight (Fo)
(WIL
Research.
2001)
High
Reproductive
Repro-
ductive/
Develop-
mental
Rat,
Crl:CD(SD)IG
SBRM/F
(n=50 FO
/group; 49-50
F1
adults/group)
Inlialation,
whole body,
vapor
0, 100, 250, 500
or 750 ppm
6 hours/day
during pre-
mating
(>70 days),
throughout
mating, and
until GD 20;
from PND 5
until weaning
of offspring
(-PND21)
NOAEL= 250
(F)
Increase in
estrous cycle
length (Fo)
(WIL
Research.
2001)
High
Page 455 of 486
-------
Target
Organ/
System
Study Type
Species/
Strain/Sex
(Number/
group)1
Exposure
Route
Doses/
Concentrations2
Duration3
Effect Dose/
Concentration
(ppm or
mg/kg-day)4
(Sex)
Effect5
Reference6
Data Quality
Evaluation7'8
Reproductive
Short-term
Mouse,
C57BL/6J,
DBA/2J and
BALB/cA,
M
(n=6/strain/gro
up)
Inlialation,
whole body,
vapor
0, 50, 110 or 250
ppm
8 hours/day,
7 days/ week
for 4 weeks
LOAEL= 50
(M)
Decreased
sperm count
and motility
and/or
increased
abnormal
sperm
(Liu et al..
2009)
High
Reproductive
Chronic
Mouse,
B6C3F1, M/F
(n=20/group)
Inlialation,
whole body,
vapor
0, 62.5, 125, 250
or 500 ppm
6.2 hours/day,
5 days/ week
for 14 weeks
NOAEL= 125
(M)
Decreased
epididymis
weight and
sperm motility
(NTP,
2011a)
High
Reproductive
Chronic
Mouse,
B6C3F1, M/F
(n=20/group)
Inlialation,
whole body,
vapor
0, 62.5, 125, 250
or 500 ppm
6.2 hours/day,
5 days/week
for 14 weeks
LOAEL= 125
(F)
Alterations in
estrous cycles
(NTP,
2011a)
High
Reproductive
Chronic
Mouse,
B6C3F1, M/F
(n=100/group)
Inlialation,
whole body,
vapor
0, 62.5, 125 or
250 ppm
6.2 hours/day,
5 days/week
for 105 weeks
NOAEL= 250
No effects on
liistopathology
of
reproductive
organs
(NTP,
2011a)
High
Reproductive
Short-term
Rat, Sprague-
Dawley, M
(n=7/group)
Intra-
peritoneal
0 or 1000
mg/kg-day
14 days
LOAEL= 1000
(M)
Decreased
epididymal
sperm count;
decreased
epididymis
and prostate +
seminal
vesicle
weights
(Xin et al..
2010)
N/A
Page 456 of 486
-------
Target
Organ/
System
Study Type
Species/
Strain/Sex
(Number/
group)1
Exposure
Route
Doses/
Concentrations2
Duration3
Effect Dose/
Concentration
(ppm or
mg/kg-day)4
(Sex)
Effect5
Reference6
Data Quality
Evaluation7'8
Respiratory
Acute
Rat
(n=10/group)
Inhalation
0, 6040, 7000,
7400 or 8500
ppm
4 hours
NOAEL= 6040
Pulmonary
edema and
emphysema
(Elf
Atochem.
1997)
N/A
Respiratory
Short-term
Rat, F344/N,
MZF
(n=10/group)
Inhalation,
whole body,
vapor
0, 125, 250, 500,
100 or 2000 ppm
6.2 hours/day,
5 days/week
for 16 days
NOAEL= 250
(M)
Nasal lesions
(including
suppurative
inflammation
and
respiratory
epithelial
necrosis)
(NTP,
2011a)
High
Respiratory
Short-term
Rat
(n=20/group)
Inhalation
0, 398, 994 or
1590 ppm
6 hours/day,
5 days/ week
for 4 weeks
NOAEL= 994
Histo-
pathological
changes in
nasal cavities
(ClinTrials.
1997b)
N/A
Respiratory
Subchronic
Rat, Wistar, M
(n=8-9/group)
Inhalation,
whole body,
vapor
0, 200, 400 or
800 ppm
8 hours/day,
7 days/ week
for 12 weeks
NOAEL= 800
(M)
No effects on
lung weight or
histopathology
(Ichihara et
al.. 2000b)
High
Respiratory
Subchronic
Rat, Sprague-
Dawley, M/F
(n=20/group)
Inhalation,
whole body,
vapor
0, 50, 300 or
1800 ppm
6 hours/day,
5 days/ week
for 8 weeks
NOAEL= 1800
No effects on
lung weight or
histopathology
(Kim et al..
1999a)
N/A
Respiratory
Chronic
Rat, Albino,
M/F
(n=30/group)
Inhalation,
whole body,
vapor
0, 100, 200, 400
or 600 ppm
6 hours/day,
5 days/ week
for 13 weeks
NOAEL= 600
No effects on
lung weight or
histopathology
(ClinTrials.
1997a)
High
Respiratory
Chronic
Rat, F344/N,
M/F
(n=20/group)
Inhalation,
whole body,
vapor
0, 62.5, 125,
250, 500 or 1000
ppm
6.2 hours/day,
5 days/week
for 14 weeks
NOAEL= 1000
No effects on
lung weight or
histopathology
(NTP,
2011a)
High
Page 457 of 486
-------
Target
Organ/
System
Study Type
Species/
Strain/Sex
(Number/
group)1
Exposure
Route
Doses/
Concentrations2
Duration3
Effect Dose/
Concentration
(ppm or
mg/kg-day)4
(Sex)
Effect5
Reference6
Data Quality
Evaluation7'8
Respiratory
Chronic
Rat, F344/N,
MZF
(n=100/group)
Inhalation,
whole body,
vapor
0, 125, 250 or
500 ppm
6.2 hours/day,
5 days/week
for 105 weeks
LOAEL= 635
mg/m3
Chronic active
nasal
inflammation
and squamous
metaplasia in
the larynx
(NTP,
2011a)
High
Respiratory
Repro-
ductive/
Develop-
mental
Rat,
Crl:CD(SD)IG
SBRM/F
(n=50 FO
/group; 49-50
F1
adults/group)
Inhalation,
whole body,
vapor
0, 100, 250, 500
or 750 ppm
6 hours/day
during pre-
mating
(>70 days),
throughout
mating, and
until sacrifice
in Fo males; or
until GD 20
and from PND
5 until
weaning of
offspring
(~PND 21) in
Fo females
NOAEL= 750
No effects on
lung weight or
histopathology
(WIL
Research.
2001)
High
Respiratory
Short-term
Mouse,
B6C3F1, M/F
(n=10/group)
Inhalation,
whole body,
vapor
0, 125, 250, 500,
1000 or 2000
ppm
6.2 hours/day,
5 days/week
for 17 days
NOAEL= 250
Lesions in the
lung and nose
(NTP,
2011a)
High
Respiratory
Chronic
Mouse,
B6C3F1, M/F
(n=20/group)
Inhalation,
whole body,
vapor
0, 62.5, 125, 250
or 500 ppm
6.2 hours/day,
5 days/week
for 14 weeks
NOAEL= 250
Cytoplasmic
vacuolization
in the nose,
larynx,
trachea, and
lung
(NTP,
2011a)
High
Page 458 of 486
-------
Target
Organ/
System
Study Type
Species/
Strain/Sex
(Number/
group)1
Exposure
Route
Doses/
Concentrations2
Duration3
Effect Dose/
Concentration
(ppm or
mg/kg-day)4
(Sex)
Effect5
Reference6
Data Quality
Evaluation7'8
Respiratory
Chronic
Mouse,
Inlialation,
0, 62.5, 125 or
6.2 hours/day.
LOAEL= 62.5
Histo-
(NTP.
High
B6C3F1, M/F
whole body.
250 ppm
5 days/week
pathological
2011a)
(n=100/group)
vapor
for 105 weeks
lesions in the
nasal
respiratory
epithelium,
larynx,
trachea, and
bronchioles
Develop-
Develop-
Rat, Wistar-
Inlialation,
0, 100 , 400 or
8 hours/day
NOAEL= 100
Decreased
(Furuhashi
N/A
mental
mental
Imamichi, F
whole body.
800 ppm
during
survival
et al.. 2006)
Effects
(n=10/group)
vapor
gestation
(GDs 0-21)
and lactation
(PNDs 1-21)
during
lactation
Develop-
Develop-
Rat, Albino
Inlialation,
0, 100, 199, 598
6 hours/day on
NOAEL= 199
Decreased
(Huntingdon
N/A
mental
mental
Crl:CD(SD)IG
whole body.
or 996 ppm
GDs 6-19;
body weight
Life
Effects
S BR, F
(n=10/group)
vapor
PNDs 4-20
gain in pups
Sciences.
1999)
Develop-
Develop-
Rat
Inlialation
0, 103, 503 or
6 hours/day on
LOAEL = 103
Decreased
(Huntingdon
N/A
mental
mental
(n=25/group)
1005 ppm
GDs 6-19;
fetal weight
Life
Effects
PNDs 4-20
Sciences.
2001)
Page 459 of 486
-------
Species/
Strain/Sex
(Number/
group)1
Effect Dose/
Target
Organ/
System
Study Type
Exposure
Route
Doses/
Concentrations2
Duration3
Concentration
(ppm or
mg/kg-day)4
(Sex)
Effect5
Reference6
Data Quality
Evaluation7'8
Develop-
Repro-
Rat,
Inlialation,
0, 100, 250 or
6 hours/day
NOAEL= 250
Decreased live
(WIL
High
mental
ductive/
Crl:CD(SD)IG
whole body.
500 ppm
during pre-
litter size (Fi
Research.
Effects
Develop-
mental
SBRM/F
(n=50 F0
/group; 49-50
F1
adults/group)
vapor
mating
(>70 days),
throughout
mating, and
until sacrifice
in males; or
until GD 20
and from PND
5 until
weaning of
offspring
(~PND 21) in
females
females)
2001)
Develop-
Repro-
Rat,
Inlialation,
0, 100, 250 or
6 hours/day
NOAEL = 100
Decreased pup
(WIL
High
mental
ductive/
Crl:CD(SD)IG
whole body.
500 ppm
during pre-
body weights
Research.
Effects
Develop-
mental
SBRM/F
(n=50 F0
/group; 49-50
F1
adults/group)
vapor
mating
(>70 days),
throughout
mating, and
until sacrifice
in males; or
until GD 20
and from PND
5 until
weaning of
offspring
(~PND 21) in
females
(Fi PND 28
males)
2001)
Page 460 of 486
-------
Target
Organ/
System
Study Type
Species/
Strain/Sex
(Number/
group)1
Exposure
Route
Doses/
Concentrations2
Duration3
Effect Dose/
Concentration
(ppm or
mg/kg-day)4
(Sex)
Effect5
Reference6
Data Quality
Evaluation7'8
Develop-
Repro-
Rat,
Inlialation,
0, 100, 250 or
6 hours/day
NOAEL = 250
Decreased pup
(WIL
High
mental
ductive/
Crl:CD(SD)IG
whole body.
500 ppm
during pre-
body weights
Research.
Effects
Develop-
SBR.M/F
vapor
mating
(F2PNDs 14
2001)
mental
(n=50 F0
(>70 days).
and 21 males)
/group; 49-50
throughout
F1
mating, and
adults/group)
until sacrifice
in males; or
until GD 20
and from
PND 5 until
weaning of
offspring
(~PND 21) in
females
Develop-
mental
Effects
Repro-
ductive/
Develop-
mental
Rat,
Crl:CD(SD)IG
S BR, M/F
(n=50 F0
/group; 49-50
F1
adults/group)
Inlialation,
whole body,
vapor
0, 100, 250 or
500 ppm
6 hours/day
during pre-
mating
(>70 days),
throughout
mating, and
until sacrifice
in males; or
until GD 20
and from
PND 5 until
weaning of
offspring
(~PND 21) in
females
NOAEL = 250
Decreased pup
body weights
(F2PNDs 14
and 21
females)
(WIL
Research.
2001)
High
Species/strain, sex of animals included in the study.
2Doses and concentrations - values were reported in 2016 Draft Risk Assessment (U.S. EPA. 2016c) for 1-BP.
Page 461 of 486
-------
3Acute exposures defined as those occurring within a single day (<24 hr). Short-term exposures are defined as 1-30 days. Subchronic exposures are defined as 30-90
days. Chronic exposures are defined as >90 days, or 10% or more of a lifetime.
4 Units are mg/m3 for inhalation exposure and mg/kg-day for oral exposure; sex is identified if one sex has a lower POD; this includes only the PODs identified by the
study authors.
5The effect(s) listed were the most sensitive effects observed for that target organ/system in that study (i.e., the effect(s) upon which the POD was based).
6This column lists the primary reference for the reported data.
'Information included in this column is the result of the data quality evaluation for all acceptable studies (those with an overall rating of high, medium or low).
Unacceptable studies are not included in this table.
8N/A: Only key and supporting studies carried forward for dose-response analysis in the 20.1.6 Draft Risk Assessment (U.S. EPA. 2016c) for 1-BP, in addition to any
new studies since that time, went through systematic review.
Page 462 of 486
-------
J.5 Carcinogenicity and Mutagenicity
There are no epidemiological studies on the effects of 1-BP exposure on human cancer.
The carcinogenicity of 1-BP has been studied in rats and mice in a two-year bioassay by the
National Toxicology Program CNTP. 2011a). Groups of 50 male and 50 female rats and mice were
exposed to 1-BP vapor at concentrations of 62.5, 125, or 250 ppm (mice) and 125, 250, or 500 ppm
(rats), 6 hours per day, 5 days per week for up to 105 weeks. Similar groups of 50 animals were
exposed to clean air in the same inhalation chambers as the control groups. All animals were
observed twice daily. Clinical findings were recorded for all animals every 4 weeks through week
93, every 2 weeks thereafter, and at the end of the studies. Rats and mice were weighed initially,
weekly for the first 13 weeks, then every 4 weeks through week 93, every 2 weeks thereafter, and
at the end of the studies. Complete necropsies and microscopic examinations were performed on
all rats and mice.
At the end of the two-year bioassay, there were treatment-related skin tumors in male rats and large
intestine tumors in female rats. Significantly increased incidence of lung tumors was found in
female mice. Based on increased incidences of tumors in rats and mice, at multiple sites and the
occurrence of rare tumors, it has been concluded that there is sufficient evidence of carcinogenicity
in experimental animals for 1-BP. Each of these tumor types is described below.
J.5.1 Skin Tumors
In male rats, there were exposure concentration treatment-related increased incidences of
keratoacanthoma, keratoacanthoma or squamous cell carcinoma (combined); and keratoacanthoma,
basal cell adenoma, basal cell carcinoma, or squamous cell carcinoma (combined). The incidences
of keratoacanthoma and of keratoacanthoma or squamous cell carcinoma (combined) in 250 ppm
(12%) and 500 ppm (12%) males were significantly increased as compared to the controls (0% and
2%), and exceeded the historical control ranges (0-8%) for inhalation studies. The incidences of
keratoacanthoma, basal cell adenoma, basal cell carcinoma, or squamous cell carcinoma
(combined) were significantly increased in all exposed groups of males (125 ppm: 14%; 250 ppm:
18%; and 500 ppm: 20%) as compared to the controls (2%) and exceeded the historical control
range (0-10%) for inhalation studies. In female rats, there were increased incidences of squamous
cell papilloma, keratoacanthoma, basal cell adenoma, or basal cell carcinoma (combined) in the
500 ppm group (8%) as compared to the control (2%). Although the increased incidences were not
significant, they exceeded the respective historical control ranges for inhalation studies.
J.5.2 Large Intestine Tumors
Large intestine tumors are rare tumors in the rat. The incidence of adenoma of the large intestine
(colon or rectum) in 500 ppm females (5/50, 10%) was significantly greater than that in the
controls (0%). The incidences in the 250 ppm (2%) and 500 ppm (4%) groups of females exceeded
the historical controls in inhalation studies (0.1%). In 250 (4%) and 500 (2%) ppm males, the
incidences of adenoma of the large intestine were slightly increased compared to that in the
Page 463 of 486
-------
controls (0%); although the increases were not statistically significant, the incidence in the 250
ppm group (4%) exceeded the historical control ranges (0-2%) for inhalation studies.
J.5.3 Lung Tumors
In the female mice, there were treatment-related increased incidences of alveolar/bronchiolar
adenoma, alveolar/bronchiolar carcinoma, and alveolar/bronchiolar adenoma or carcinoma
(combined). The incidence of alveolar/bronchiolar adenoma in 250 ppm females (20%) and the
incidences of alveolar/bronchiolar carcinoma in 62.5 ppm (14%) and 125 ppm (10%) females were
significantly increased as compared to the controls (0-2%). The incidences of alveolar/bronchiolar
adenoma or carcinoma (combined) were significantly increased in all exposed groups (18%, 16%
and 28%) in low-, mid- and high-dosed groups) as compared to the controls (2%).
J.5.4 Pancreatic Tumors
The evidence that 1-BP exposure was associated with an increased incidence of pancreatic islet
adenoma in male rats was equivocal. Although the incidences of pancreatic islet adenoma were
significantly increased in all exposed groups compared to the chamber controls (0%, 10%, 8%,
10%>), the incidences were within the historical control ranges for inhalation studies (0% to 12%).
The incidences of pancreatic islet carcinoma in exposed male rats were not significantly different
from that in the chamber controls and were not considered treatment related. The incidences of
pancreatic islet adenoma or carcinoma (combined) were significantly increased only in the low-
dose (20%) and mid-dose groups (18%) as compared with the chamber controls (6%); only the
incidence in the low-dose group (20%) exceeded the historical control ranges for inhalation studies
(6% to 18%).
J.5.5 Malignant Mesothelioma
There were increased incidences of malignant mesothelioma in male rats exposed to 1-BP as
compared to the chamber controls: control, 0%; low-dose, 4%; mid-dose, 4%; and high-dose, 8%.
The incidence of malignant mesothelioma in high-dose group (8%) was significantly greater than
that of the chamber controls (0%) and exceeded that of the historical controls (0-6%) in inhalation
studies. The overall strength of this evidence was considered equivocal because the increased
incidence in the high-dose (500 ppm) group was s barely outside the historical control range (0% to
6%).
Under the conditions of these 2-year inhalation studies, there was clear evidence of carcinogenic
activity of 1-BP in female F344/N rats based on increased incidences of adenoma of the large
intestine. Increased incidences of skin neoplasms may also have been related to 1-BP exposure.
There was some evidence of carcinogenic activity of 1-BP in male F344/N rats based on the
increased incidences of epithelial neoplasms of the skin (keratoacanthoma, squamous cell
carcinoma, and basal cell neoplasms). Increased incidences of malignant mesothelioma and
pancreatic islet adenoma and carcinoma (combined) may also have been related to 1-BP exposure.
There was clear evidence of carcinogenic activity of 1-BP in female B6C3F1 mice based on
increased incidences of alveolar/bronchiolar neoplasms. There was no evidence of carcinogenic
activity of 1-BP in male B6C3F1 mice exposed to concentrations of 62.5, 125, or 250 ppm 1-BP.
Page 464 of 486
-------
Based on increased incidences of tumors in rats and mice, at multiple sites and the occurrence of
rare tumors, it has been concluded that there is sufficient evidence of carcinogenicity in
experimental animals for 1-BP. The compound has been considered to be "reasonably to be
anticipated as a human carcinogen" and will be listed in the next issue of Report on Carcinogens of
the National Toxicology Program (NTP. 2013a).
The tumor data on the skin, large intestine and lung in male and female rats and female mice
(TableApx J-3) may be used for quantitative assessment of the potential risk of humans exposed
to 1-BP.
Table Apx J-3. Tumors induced by 1-BP in Rats and Mice
Animal
Tumor
Concentration
(ppm)
Incidence
F344/N rats, male
Skin (keratoacanthoma,
squamous-cell carcinoma, basal-cell
adenoma or carcinoma combined)
0
1/50 (2%)
125
7/50* (14%)
250
9/50** (18%)
500
10/50** (20%)
Trend
£>=0.003
F344/N rats, female
Large intestine (colon or rectum adenoma)
0
0/50 (0%)
125
1/50 (2%)
250
2/50 (4%)
500
5/50* (10%)
Trend
p=0.004
B6C3F1 mice, female
Lung (alveolar /bronchiolar adenoma or
carcinoma combined)
0
1/50 (2%)
62.5
9/50** (18%)
125
8/50* (16%)
250
14/50*** (28%)
Trend
p<0.001
*p<0.05; **/?<0.01; ***/?<0.001
J.5.6 Genotoxicity
1-BP has been shown to bind covalently to DNA to form N7-propyl guanine adducts in an in vitro
system using 2'deoxyguanosine and calf thymus DNA, with adduct formation increasing in
relation to 1-BP concentration (Thapa et al.. 2016). In another study with calf thymus DNA (Lee et
al.. 2007). adduct formation was rapid (peaked within 2 hr) and was not affected by addition of
liver homogenates, suggesting that the adducts were formed directly by 1-BP. In vivo, 1-BP
produced N7-propyl guanine adducts in liver > spleen > kidney > lung > testis of treated rats
(Nepal et al.. 2019). Adduct levels in all of these tissues increased with dose and number of days of
treatment. No adducts were found in the heart with any dosing regimen tested. These studies show
that 1-BP can interact with DNA to form N7-propyl guanine adducts, but there is no established
relationship between N7-propyl guanine adducts and mutagenic effects (e.g., see Boy sen (2009)).
Page 465 of 486
-------
Mixed results have been reported in genotoxicity tests using bacteria. 1-BP was mutagenic in a
dose-dependent manner in Salmonella typhimurium (S. typhimurium) strains TA100 and TA1535
when the assay was conducted using closed chambers/desiccators specifically designed for testing
volatile substances (Barber et al.. 1981). The data suggest that 1-BP may be a direct-acting
mutagen since similar responses were observed both with and without metabolic activation. An
NTP peer review committee considered Barber (1981) to be a well conducted study (NTP. 2013a).
A second study using a closed test system found no evidence of mutagenicity (BioReliance. 2015).
but the specific method used to achieve the closed system in this study may have been less
efficient. See Appendix J.5.7 below for a detailed comparison of these two studies.
A number of other studies reported negative responses in S. typhimurium and Escherichia coli (E.
coif) (NTP. 2011a; Kim et al.. 1998; Elf Atochem. 1993b). While these tests may not have been
conducted in closed systems, the occurrence of cytotoxicity at high concentrations in the (NTP.
2011a; Kim et al.. 1998) study suggests that sufficient quantities of 1-BP were present to induce
that effect, and therefore, that the lack of observed mutagenicity in the study did not result from
lack of 1-BP in the test medium, but rather from lack of mutagenic activity of 1-BP.
1-BP was shown to induce base-pair mutations in the L5178Y mouse lymphoma cell assay, with
and without S9 metabolic activation (Elf Atochem. 1996b). Using the comet assay, (Toraason et
al.. 2006) demonstrated DNA damage in human leukocytes exposed to 1 mM 1-BP in vitro; there
was also equivocal evidence of DNA damage in leukocytes from workers exposed to 1-BP on the
job. In contrast to the positive in vitro studies, negative results were reported with in vivo
micronucleus assays in mice exposed to 1-BP via intraperitoneal (ip) injection (Kim et al.. 1998).
and in rodents exposed via inhalation (NTP. 201 la; Elf Atochem. 1995). A compilation of in vivo
micronucleus data by (Benigni et al.. 2012) showed a low correlation between in vivo micronucleus
data and carcinogenicity, however, suggesting a potential for "false negative" predictions. 1-BP
also produced negative results in dominant lethal mutation assays conducted in ICR mice (Yu et
al.. 2008) and Sprague-Dawley rats (Saito-Suzuki et al.. 1982).
Mutation frequencies at the ell gene in the liver, lung, and colon were determined in groups of
female B6C3F1 heterozygous transgenic Big Blue® mice (mutations were evaluated in 6
mice/group) that were exposed by whole-body inhalation to target 1-BP vapor concentrations of 0
(concurrent control), 62.5, 125, or 250 ppm (mean measured concentrations of 0, 62.8, 125, and
258 ppm, respectively) for 6 hours/day, either 5 or 7 days/week for 4 weeks (Stellies et al.. 2019;
Young. 2016). Liver, lung, and colon tissues were collected for DNA isolation and determination
of mutation frequencies on the third day after the final exposure. Compared with controls, groups
exposed to 1-BP showed no statistically significant elevations in mutation frequencies at the ell
gene in liver, lung, or colon and showed no treatment-related effects on clinical observations, body
weights, food consumption, or organ weights. Mutation frequencies in the liver, lung, and colon
from concurrent negative control mice were comparable to values found in historical negative
controls. In a positive control group that received 40 mg/kg of the direct-acting mutagen ethyl
nitrosourea by gavage on study days 1, 2, and 3, mutation frequencies on study day 31 were
statistically significantly elevated in liver, lung, and colon, thus demonstrating the ability of this
test system to detect mutations. Of note, despite the negative results it is unclear whether the
Page 466 of 486
-------
protocol was fully adequate to address the intended outcome. The maximum tolerated dose was not
evaluated, and the sensitivity of the test system is dependent on the duration of the post-exposure
observation period which may be insufficient for slower-dividing tissues.
Mixed results have been reported in genotoxicity tests using bacteria. 1-BP was mutagenic in a
dose-dependent manner in Salmonella typhimurium (S. typhimurium) strains TA100 and TA1535
when the assay was conducted using closed chambers/desiccators specifically designed for testing
volatile substances (Barber et al.. 1981). The data suggest that 1-BP may be a direct-acting
mutagen since similar responses were observed both with and without metabolic activation. A
number of other studies reported negative responses in S. typhimurium and Escherichia coli (E.
colt) but some of these studies were not conducted using the appropriate methodology {i.e.,
treatment and incubation in a closed chamber) for testing a volatile substance (NTP. 2011a; Kim et
al.. 1998; Elf Atochem. 1993b). An NTP peer review committee considered Barber (1981) to be a
well conducted study (NTP. 2013a).
1-BP was shown to induce base-pair mutations in the L5178Y mouse lymphoma cell assay, with
and without S9 metabolic activation (Elf Atochem. 1996b). Using the comet assay, (Toraason et
al.. 2006) demonstrated DNA damage in human leukocytes exposed to 1 mM 1-BP in vitro; there
was also limited evidence that leukocytes from workers exposed to 1-BP may present risk for
increased DNA damage. In contrast to the positive in vitro studies, negative results were reported
with in vivo micronucleus assays in mice exposed to 1-BP via intraperitoneal (ip) injection (Kim et
al.. 1998). and in rats exposed via inhalation (NTP. 2011a; Elf Atochem. 1995). It should be noted,
however, that a recent compilation of in vivo micronucleus data by (Benigni et al.. 2012) showed a
low correlation between in vivo micronucleus data and carcinogenicity, suggesting a potential for
"false negative" predictions. 1-BP was also produced negative results in dominant lethal mutation
assays conducted in ICR mice (Yu et al.. 2008) and Sprague-Dawley rats (Saito-Suzuki et al..
1982).
Several known or proposed metabolites of 1-BP have been shown to be mutagenic (NTP. 2014;
IARC. 2000. 1994). For example, both glycidol and propylene oxide are mutagenic in bacteria,
yeast, Drosophila, and mammalian cells. These compounds have also been shown to induce DNA
and chromosomal damage in rodent and human cells, and can form DNA adducts in vitro.
a-Bromohydrin and 3-bromo-l-propanol were mutagenic in the S. typhimurium reversion assay,
and 3-bromo-l-propanol and l-bromo-2-propanol induced DNA damage in E. coli. The available
in vivo test results for glycidol indicate that it induces micronucleus formation, but not
chromosomal aberrations in mice. Studies of propylene oxide indicated chromosomal damage
evidenced by positive responses for micronucleus induction in mouse bone marrow and
chromosomal aberration tests; DNA damage was evident in the sister chromatid exchange (SCE)
assay.
Page 467 of 486
-------
Table Apx J-4. Key Genotoxicity Studies on 1-BP
Species (test system) and
administration route/
exposure duration
(for in vivo)
Endpoint
Results
Reference
Data Quality
With
activation
Without
activation
Cell-free in vitro
Calf thymus DNA
DNA binding and
adduct formation
+
N/A
(Thaoa et al.. 2016)
High
Prokaryotic organisms:
S. tvphimurium TA98, TA100,
TA1535, TA1537, TA1538
Reverse mutation
(open test
system)
(open test
system)
(Barber et al.. 1981)
High
S. tvphimurium TA100, TA1535
Reverse mutation
+
(closed test
system)
+
(closed test
system)
(Barber et al.. 1981)
High
S. tvphimurium TA97, TA98,
TA100, TA 1535
Reverse mutation
-
-
(NTP. 2011a)
High
Eschericliia coli Wp2
uvrA/pKMlOl
Reverse mutation
-
-
(NTP. 2011a)
High
S. tvphimurium TA98, TA100,
TA 1535, and TA 1537
Reverse mutation
-
-
(BioReliance. 2015)
Medium
Eschericliia coli Wp2
uvrA/pKMlOl
Reverse mutation
-
-
(BioReliance. 2015)
Medium
Mammalian cells in vitro:
Human hepatoma cell-line
(HepG2)
DNA damage and
repair, single strand
breaks
-
N/A
(Hassoiclcr et al.. 2006)
High
Human hepatoma cell-line
(HepG2)
DNA damage and
repair, repair activity
-
N/A
(Hassoiclcr et al.. 2006)
High
Mouse lymphoma cell-line
(L51785Y)
Base-pair mutations
+
+
(Elf Atochem. 1996b)
High
Human leukocyte cells
DNA damage and
repair
+
N/A
(Toraason et al.. 2006)
High
Mammalian in vivo:
3-month inhalation study in
B6C3F1 mice
Micronucleus assay
-
N/A
(NTP. 2011a)
High
4-week inhalation study in Big
Blue® B6C3F1 transgenic mice
Mutation frequencies
at ell gene
-
N/A
(Stellies et al.. 2019)
(Youne. 2016)
Medium
3-day intraperitoneal injection
in SD rats
DNA binding and
adduct formation
+
N/A
(Nenal et al.. 2019)
High
Epidemiological
Page 468 of 486
-------
Human leukocyte cells
DNA damage and
repair
+/-
N/A
(Toraason et al.. 2006)
Medium
+ = positive results; - = negative results; +/- = equivocal
J.5.7 Comparison of Bacterial Reverse Mutation Studies
Two bacterial reverse mutation studies of 1-BP both used test systems characterized as 'closed' but
yielded different results for mutagenicity. In a study by Barber et al. (1981). a positive
mutagenicity result was observed for 1-BP in Salmonella typhimurium strains TA 1535 and TA
100 (but not TA 1537, TA 1538, or TA 98) in the presence and absence of metabolic activation. In
contrast, a study by BioReliance (2015) found no evidence of mutagenicity in S. typhimurium
strains TA 98, TA 100, TA 1535, and TA 1537 or Escherichia coli strain WP2 uvrA (a DNA
repair-deficient strain) in the presence or absence of metabolic activation.
In many respects, both studies adhered to OECD TG 471 (Bacterial Reverse Mutation Test
(2019o)), although only the BioReliance (2015) study indicated that it conformed to the test
guidelines. However, the procedures outlined in the guideline pertain primarily to standard plate
incorporation or preincubation methods; OECD TG 471 (2019o) notes that certain classes of
mutagens (including volatile chemicals, such as 1-BP) are not detected using these methods. In
these 'special cases', the guideline recommends the use of alternative approaches. The studies by
Barberet al. (1981) and BioReliance (2015) used different methods in an effort to circumvent
issues with respect to the volatility of the test substance.
The primary differences between the two studies were the method of exposure, the duration of
exposure of test organisms to 1-BP, methods used to control for the volatility of the test substance,
and differences between the studies in maintenance of effective concentrations of 1-BP during test
organism exposure. Barber et al. (1981) indicated that the study followed the standard methods
originally described by Ames et al. (1975); only the method of chemical application was modified.
Rather than using a standard plate-incorporation test, Barber designed a chemically inert, closed
incubation system to test the mutagenicity of volatile chemicals, applied as a vapor. The test
system consisted of several Pyrex containers, each designed to accommodate a metal rack housing
up to 12 glass plates. The glass plates were considered chemically inert with respect to adsorption
of halogenated hydrocarbons, in contrast to plastic plates. The Pyrex containers were fitted with
Teflon tops with valve and septum assemblies. A blank plate, containing only sterile distilled
water, was inserted into each test system and was used for measurement of the aqueous 1-BP
concentration at the end of exposure. Test plates were prepared by mixing an inoculum of an
overnight growth culture (growth phase not reported) with top agar (with or without S9 mix) and
pouring the mixture onto a plate containing Vogel-Bonner Medium E and agar. The plates were
allowed to solidify at room temperature and then placed onto a stainless-steel rack. The racks filled
with plates were placed into the Pyrex containers and the containers were sealed. Under a partial
vacuum, the liquid test substance was added through the septum using a syringe and was observed
to vaporize, after which time air was reintroduced into each incubation system. The test systems
were then incubated at 37°C for 48 hours, with continuous stirring to mix the internal atmosphere.
Page 469 of 486
-------
Samples of the vapor, as well as aqueous samples, were taken from the test systems at the end of
the 48-hour incubation period and analyzed by gas-liquid chromatography (GLC). The GLC results
for the aqueous samples were used to calculate the amount of chemical dissolved per plate {i.e.,
1.1,2.3,4.9, 9.0, or 20.3 |imoles/plate, or about 0, 140, 280, 600, 1100, and 2500 |ig/plate, based
on a molecular weight for 1-BP of 122.9 g/mol). Numbers of revertant colonies were tabulated
using a colony counter at the end of the 48-hour incubation period. The study authors indicated that
advantages of using this system included: 1) an enhanced ability to detect mutagenicity of volatile
chemicals in the closed system compared to the standard plate-incorporation test; 2) decreased
exposure of laboratory personnel to volatile chemicals that are potentially mutagenic; 3) better
simulation of actual exposure (frequently as a vapor); and 4) the purity of the test substance is
obtained as part of the analytical result, minimizing the chance of false positives due to mutagenic
impurities.
The BioReliance (2015) study tested the mutagenicity of 1-BP using a preincubation method, as
described by Yahagi et al. (1977). After an initial toxicity-mutation assay, two confirmatory
mutagenicity assays were conducted. Target concentrations of 1-BP tested were 1.5-5000 |ig/plate
for the initial toxi city-mutation assay and 50-5000 |ig/plate for the confirmatory mutagenicity
assays. To prepare the dosing formulations, the test substance was diluted in ethanol; the test
substance was determined to be stable in this solvent at room temperature for at least 3.25 hours.
Dosing formulations were prepared immediately before use. For the repeat test of the confirmatory
assay, dilutions of 1-BP were prepared in screw-capped tubes with minimal headspace; it was
unclear whether these measures to reduce volatilization were taken during the first confirmatory
assay due to a lack of documentation. To prepare the preincubation solutions, the diluted test
substance or vehicle (ethanol), S9, or sham mix (containing phosphate buffer), and the tester strain
(late log growth phase) were added to glass culture tubes preheated to 37±2°C. Tubes receiving the
test substance were capped using screw caps (amount of headspace not reported) during the
preincubation period, which lasted for 90±2 minutes at 37±2°C. Samples for analysis of test
substance concentrations by gas chromatography (GC) were taken from the dosing formulations, as
well as from the solutions in preincubation tubes (without metabolic activation) at the beginning
and end of the preincubation period, from the vehicle control and lowest and highest exposure
concentrations (positive controls not evaluated). Measured concentrations of 1-BP in dosing
formulations met acceptability criteria (85% to 115% of target concentrations, with < 5% relative
standard deviation [RSD]), except for the low concentration of the second confirmatory assay
(>5%) RSD). A small peak of test substance was detected in the vehicle control dosing formulation
used in the second confirmatory assay. Measured concentrations of 1-BP in preincubation tubes
were much lower than target (nominal) concentrations. For the first confirmatory assay, the
measured concentrations of 1-BP at the beginning of the preincubation period were 37% and 9% of
the target concentrations at the lowest and highest exposure concentrations, respectively; by the
end of the preincubation period, the measured concentrations had declined to 3% and 2%,
respectively, of the target concentrations. For the second confirmatory assay, the measured
concentrations at the beginning of the preincubation period were 7% and 4% of the target
concentrations at the lowest and highest exposure concentrations, respectively; the measured
concentrations at the end of the preincubation period were 5% and 3%, respectively, of the target
concentrations. Following preincubation, top agar was added to the tube and the mixture was
Page 470 of 486
-------
overlaid onto minimal bottom agar (Vogel-Bonner minimal medium E). Once solidified, plates
containing the test substance were inverted and placed in desiccators by dose level for 48 to 72
hours at 37±2°C prior to scoring. Additional plates were prepared using only test substance,
vehicle, S9, or sham mix to confirm the sterility of these solutions. Revertant colonies were
counted either entirely by automatic colony counter or entirely by hand unless the plate exhibited
toxicity (except for positive controls). Plates not scored immediately following the incubation
period were stored at 2-8°C until counting occurred. Although it was noted in the study report that
the use of screw caps, intended to prevent evaporation of the test substance, was not documented in
the initial confirmatory assay (and the assay was repeated), the conclusion of both confirmatory
assays was the same; no mutagenicity was detected in any strain in the presence or absence of
metabolic activation.
In some regards, there were similarities between the two studies. Both studies tested at least 5
concentrations of the test substance, with negative and standard, non-volatile positive controls used
(see below for additional information). However, neither study used volatile positive control
substances for explicitly demonstrating that their specific test protocols were optimized for
detection of volatile chemical mutagens. The purity of the test substance was > 99% in both
studies. Although both studies used at least 5 strains of bacteria, only the BioReliance study (2015)
included a DNA repair-deficient strain of E. coli. In both studies, the metabolic activation system
used S9 from Aroclor-induced rat livers and plates were incubated for 48 to 72 hours prior to the
scoring of revertant colonies. The BioReliance study (2015) used target exposure concentrations up
to 5000 |ig/plate, as recommended by test guidelines; the highest concentration of 5000 |ig/plate
was determined to be cytotoxic to all strains in the second confirmatory mutagenicity test. In
contrast, Barber et al. (1981) tested concentrations up to 20.3 |imoles/plate (approximately 2500
|ig/plate based on a molecular weight for 1-BP of 122.9 g/mol) and detected mutagenicity even in
the absence of cytotoxicity. The criteria for a positive or negative result were somewhat different
for the two studies. Barber et al. (1981) indicated that a result was determined to be positive based
on observed increases in the numbers of revertant colonies per plate in comparison to negative
controls (not further specified). Statistical analyses {i.e., Student's t-test tables) were used to
determine the minimum significant number of revertants per plate for each strain (data not shown),
which was used to calculate the minimum vapor concentration with a positive result {i.e.,
"minimum detectable vapor concentration," equivalent to 31.2 ppm for TA 1535 and 106.5 ppm
for TA 100). The BioReliance study (2015) stated that a result was deemed positive if there was a
dose-related increase in the mean number of revertants per plate in at least one strain at two
increasing concentrations of the test substance; a three-fold increase in the mean number of
revertants was required for S. typhimurium strains TA 1535 and TA 1537, while a two-fold change
was considered positive for all other strains tested. If the criteria for the BioReliance study (2015)
were applied to the data provided by Barber et al. (1981). 1-BP would be deemed mutagenic in
strains TA 1535 and TA 100 in the presence and absence of metabolic activation (mean data were
shown only for S. typhimurium strains TA 1535, TA 98, and TA 100); this is the same conclusion
reached by Barber et al. (1981).
The guideline pertaining to this type of assay (OECD 471; (2019o)) indicates that a result can be
considered positive for mutagenicity based on observed concentration-related increases in
Page 471 of 486
-------
revertants over the range of concentrations tested, and/or a reproducible increase in the number of
revertants/plate at one or more concentrations in at least one strain with or without metabolic
activation (OECD. 1997). The OECD 471 (2019o) test guideline recommends that biological
relevance be considered first; statistical analyses may also be used, but should not be the sole
determinant for identifying a positive response. Therefore, although the two studies differed with
respect to the classification of a positive versus a negative response, these differences do not
suggest that one study followed guideline recommendations while the other did not. The Barber et
al. (1981) study used statistics to determine vapor concentrations corresponding to a significantly
increased number of revertants. Although the BioReliance (2015) study did not use statistical
methods to evaluate mutagenicity, specific criteria for identifying a positive result were provided in
the study report. These criteria closely adhere to those set forth in the guidelines, as described
above.
In both studies, standard (non-volatile) chemicals were used as positive controls. Barber et al.
(1981) used 2-aminoanthracene as a positive control for all strains when metabolic activation was
used. In the absence of activation, positive controls were ICR-191 for S. typhimurium TA 98,
methyl-N-nitro-N'-nitrosoguanidine for strains TA 100 and TA 1535, 9-aminoacridine for TA
1537, and picrolonic acid for TA 1538. Positive and negative control data were provided by Barber
et al. (1981); however, no criteria for establishing the validity of the positive control data were
reported. For the BioReliance study (2015). 2-aminoanthracene was also identified as the positive
control substance for all strains tested in the presence of metabolic activation. The positive controls
used in the absence of metabolic activation included 2-nitrofluorene for S. typhimurium TA 98,
sodium azide for strains TA 100 and TA 1535, 9-aminoacridine for TA 1537, and methyl
methanesulfonate for E. coli WP2 uvrA. The study report specified that positive controls were
subjected to the preincubation process and plated concurrently with each assay (in duplicate in the
initial toxicity-mutagenicity assay and in triplicate for subsequent confirmatory assay). The
BioReliance study (2015) indicated that the mean number of revertants/plate for each positive
control needed to be at least three times higher than the mean value for the respective vehicle
control group for the mutagenicity test to be considered valid. Based on this criteria, positive
controls responded appropriately in both the study by Barber et al. (1981) and in all three assays in
the BioReliance study (2015). The mean numbers of revertants per plate that were observed for
negative and positive controls are provided in TableApx J-5.
TableApx J-5. Comparison of Mean Numbers of Revertants/Plate for Controls in Reverse
Mutation Assays
Mean numbers of revertants/plate for controls in reverse mutation assays
Species and Strain
Barber et al. (1981)
BioReliance (2015)"
Negative control
Positive control
Negative control
Positive control
- S9
+ S9
- S9
+ S9
- S9
+ S9
- S9
+ S9
S. typliimurium TA 98
38
38
170
415
22
32
768
490
S. typliimurium TA 100
85
96
285
678
106
100
1057
554
S. typliimurium TA 1535
20
19
148
267
15
31
463
105
S. typliimurium TA 1537
6
9
265
402
6
5
115
87
Page 472 of 486
-------
S. typhimurium TA 1538
8
21
72
495
NT
NT
NT
NT
E. coli WP2 uvrA
NT
NT
NT
NT
32
41
614
402
"Values are provided for the repeat (second) confirmatory assay of BioReliance (BioReliance. 20151. which
was the only assay that documented the use of screw-capped tubes for preparation of dosing formulations.
NT = This strain was not tested for mutagenicity.
In summary, the studies by Barber et al. (1981) and BioReliance (2015) conformed to most of the
recommendations provided in OECD TG 471 (2019o). The major differences in experimental
design between the two studies are the method of test substance application (vapor exposure of
plated bacteria for 48 hours in the Barber et al. study (1981) versus aqueous preincubation
exposure for 90 minutes in the BioReliance study (2015) study and the methods used to achieve a
'closed' system to account for the inherent volatility of 1-BP (fully enclosed test chamber versus
preparation of solutions in screw-capped tubes). Although the guideline indicates that volatile
chemicals should be considered special cases, the alternative methods that should be used to test
these types of test substances are not outlined in OECD TG 471 (2019o). It is likely that the varied
mutagenicity results from the two studies {i.e., positive results in the Barber et al. study (1981)
study and negative results in the BioReliance study (2015) are due to differences in the methods
used for exposure and to compensate for the volatility of 1-BP in the bacterial reverse mutation
assay.
Based on the following primary differences in methodology, the preincubation exposure test by
BioReliance study (2015) had inadequate sensitivity to assess the mutagenic potential of volatile
chemicals such as 1-BP, in contrast to the closed system plate vapor exposure test by Barber et al.
(1981):
1. The BioReliance study report (2015) stated that "The test system was exposed to the test
article via the preincubation methodology described by Yahagi et al. (1977)" but this
method was not designed to retain a volatile test substance such as 1-BP within the test
system during preincubation (prior to plating) with the bacterial test strains. In contrast, the
Barber et al. (1981) study was explicitly designed to retain vapors of the volatile 1-BP test
substance in contact with the bacterial test strains throughout plate incubation.
2. The BioReliance study (2015) study attempted to circumvent the volatility of 1-BP by
using screw-capped tubes for test substance dilutions (documented in the second
confirmatory assay only) and during the 90-minute preincubation period in contact with test
strains (prior to plating). While the use of minimal headspace was documented for
preparation of dosing formulations, it was unclear whether preincubation tubes contained
minimal headspace; in the absence of this precaution, 1-BP would be expected to volatilize
into the headspace. In contrast, the closed system used in the Barber et al. (1981) study
generated conditions that permitted the test strains to be exposed to 1-BP as a vapor for the
entirety of the 48-hour exposure period {i.e., without loss due to volatility); analyses of 1-
BP in aqueous samples from blank incubation plates by GLC were used to calculate the 1-
BP concentrations in plates.
3. The results of analytical measurements of 1-BP suggest that bacteria were exposed to much
higher concentrations of 1-BP in the study that found evidence of mutagenicity in two of
five bacterial strains (Barber et al.. 1981) than in the study that found no evidence of
Page 473 of 486
-------
mutagenicity in five bacterial strains (BioReliance. 2015). Barber et al. (1981) tested
measured concentrations up to 20.3 |imoles/plate (approximately 2500 |ig/plate based on a
molecular weight for 1-BP of 122.9 g/mol) and detected mutagenicity in two of five
bacterial strains in the absence of cytotoxicity. In the BioReliance study (2015) study,
analytical measurements by GC confirmed that concentrations of 1-BP in dosing
formulations were within 85-115% of target concentrations. However, despite the use of
screw-capped tubes to reduce 1-BP loss via volatilization during preincubation with the
bacterial test strains, analytical concentrations of 1-BP in preincubation tubes during the
BioReliance study (2015) confirmatory assays were far below target, with 4-37% of target
concentrations at the beginning of the preincubation period and 2-5% of target
concentrations by the end of the preincubation period. At the highest target exposure
concentration of 5000 |ig/plate, the measured concentrations during preincubation
correspond to approximately 100-450 |ig/plate (2-9% of the target concentration) in the
BioReliance study (2015) and no evidence of mutagenicity was seen at this or lower
concentrations.
4. The duration of exposure of bacteria to 1-BP was much longer in the study that showed
mutagenicity from 1-BP exposure Barber et al. study (1981) than in the study that found no
evidence of mutagenicity from 1-BP exposure (BioReliance. 2015). The closed system used
in the positive Barber et al. (1981) study generated conditions that permitted the tester
strains to be exposed to 1-BP as a vapor for the entirety of the 48-hour exposure period
{i.e., without loss due to volatility). In contrast, bacteria were exposed to 1-BP in solution
for 90 minutes in the negative BioReliance study (2015).
5. Neither Barber et al. (1981) nor BioReliance (2015) included volatile positive control
chemicals in their assays. This does not appear to be an issue for the Barber et al. study
(1981). which demonstrated mutagenicity for the volatile 1-BP test substance and for six
other volatile halogenated alkane solvents in the presence and absence of metabolic
activation. However, given that the Barber et al. study (1981) method was sufficient to
detect the mutagenicity of 1-BP and related volatile chemicals, but the BioReliance study
(2015) method found no evidence of 1-BP mutagenicity and did not show that their method
could detect mutagenicity of volatile positive controls, there is uncertainty that the
BioReliance study (2015) protocols and specific methodology were capable of adequately
assessing the mutagenic potential of 1-BP. Thus, in the absence of data for volatile positive
control chemicals43 in the BioReliance study (2015) study, it is possible that the lack of
demonstrated 1-BP mutagenicity in this study was a false negative.
The differences in results, including both cytotoxicity and mutagenicity, between these two studies
(described above and summarized in Table Apx J-6 ) suggest that the design of the experimental
43 For examples of volatile positive control mutagens see Hughes et al.(1987). which was cited by OECD TG 471
(2019O1 as an appropriate method for testing of gaseous or volatile substances.
Page 474 of 486
-------
system used for exposure and retention of the volatile test substance within the test system
significantly influenced the response of the test organisms.
TableApx J-6. Comparison of Mutagenicity Studies of 1-BP
Metric
Barber et al. (1981)
BioReliance (2015)
OECD (1997)
Doses
Measured 1-BP
concentrations were 0, 1.1,
2.3,4.9, 9.0, and 20.3
|imolcs/platc (equivalent to
approximately 0, 140, 280,
600, 1100, and 2500
Hg/plate).
There was no indication of
cytotoxicity at the highest
tested concentration.
Target 1-BP concentrations were 0, 1.5,
5.0, 15, 50, 150, 500, 1500, and 5000
Hg/plate (initial toxicity-mutagenicity
assay); 0, 50, 150, 500, 1500, 2000,
3000, and 5000 |ig/plate (confirmatory
mutagenicity assays). 1-BP
concentrations measured in confirmation
mutagenicity assay preincubation tubes
at the beginning and end of the 90-
minute exposure were much lower than
target (see row "Compound dose
confirmation and purity") and much
lower than the highest test concentration
used in the studv bv Barber et al. (1981).
In the initial assay, cytotoxicity was
observed at 5000 ng/plate (all strains);
cytotoxicity was also observed at 3000
and 5000 |ig/plate in the repeat of the
confirmatory assay.
At least 5 test concentrations of
the test substance should be
used. The recommended highest
test concentration for non-
cytotoxic substances is 5000
Hg/plate; or, for non-cytotoxic
substances that are insoluble at
that concentration a
concentration(s) that is insoluble
in final treatment mixture.
Cytotoxic substances should be
tested up to a cytotoxic
concentration.
Negative
controls
Plates in a closed system
with no added test or
positive control chemical
With the exception of not
adding chemical to the
system, untreated controls
were treated the same as
treatment groups. Negative
controls were used for each
strain, with and without
metabolic activation.
Average spontaneous
reversion rates from
negative control plates were
reported.
Exposure to vehicle only (ethanol) in
preincubation tubes
Negative controls were included for each
strain, with and without activation, and
were treated the same as treatment
groups. Raw data (number of revertant
colonies per plate) were provided for
negative controls.
In the repeat of the confirmatory assay, a
small peak of the test substance was
detected in the vehicle control sample
(-0.03 mg/mL). This was noted as a
study deviation.
Concurrent strain-specific
negative controls, with and
without metabolic activation
should be included in each
assay. Negative controls,
consisting of solvent or vehicle
alone, without test substance,
should be included and should
otherwise be treated the same as
treatment groups.
Positive
controls
With activation: 2-
Aminoanthracene (all
strains). No mutagen
requiring activation by
microsomal enzymes was
tested.
Without activation: ICR-191
for Salmonella tvphimurium
With activation: 2-Aminoanthracene (all
strains). No mutagen requiring activation
by microsomal enzymes was tested;
however, each bulk preparation of S9
was assayed for its ability to metabolize
benzo(a)pyrene to forms mutagenic to S.
tvphimurium TA 100.
Concurrent strain-specific
positive controls, with and
without metabolic activation
should be included in each
assay. Examples of chemicals
that can be used as positive
controls in the presence and
absence of metabolic activation
are recommended by guideline
Page 475 of 486
-------
Metric
Barber et al. (1981)
BioReliance (2015)
OECD (1997)
TA 98, methyl-N-nitro-N'-
nitrosoguanidine for strains
TA 100 and TA 1535, 9-
aminoacridine for TA 1537,
and picrolonic acid for TA
1538. 9-Aminoacridine and
ICR-191 are listed as strain-
specific positive controls for
TA 1537 and TA 97 (but not
TA 98) according to OECD
TG 471. The other
chemicals are not listed in
OECD TG 471.
The solvent(s) used for
positive control substances
were not specified. No
criteria were provided for a
valid response of positive
controls.
Without activation: 2-Nitrofluorene for
S. tvphimurium TA 98, sodium azide for
strains TA 100 and TA 1535, 9-
aminoacridine for TA 1537, and methyl
methanesulfonate for Escherichia coli
WP2 uvrA. All except methyl
methanesulfonate for E. coli WP2 uvrA
were listed as strain-specific positive
controls according to OECD TG 471.
Positive controls were diluted in DMSO
except sodium azide, which was diluted
in sterile water. The study indicated that
for the test to be valid, positive controls
had to show a 3-fold increase in the
number of revertants compared to the
respective vehicle control; however,
there were no vehicle controls for
DMSO or water.
(other appropriate reference
substances may be used). It is
noted that 2-aminoanthracene
should not be used as the sole
indicator of the efficacy of the
S9 mix; each batch should also
be characterized using a
mutagen that requires metabolic
activation by microsomal
enzymes (i.e., benzo(a)pyrene,
dimethylbenzanthracene).
Compound
dose
confirmation
& purity
Purity of 1-BP (as per GLC)
= 99.85%
Dose confirmation: Plates
containing only sterile
distilled water were
included in the closed
system containers for GLC
analysis of aqueous 1-BP
concentrations at the end of
the 48-hour incubation
period. Samples of the vapor
were also taken from the
closed system containers at
the end of the 4 8-hour
incubation period and
analyzed by GLC. The GLC
results from the aqueous
samples were used to
calculate the amount of
chemical dissolved per
plate.
Purity of 1-BP (determined by sponsor)
> 99%
Dose confirmation: Samples of dosins
formulations and preincubation solutions
(at 0 and 90 minutes) were analyzed by
GC (vehicle control, low- and high-dose
groups only). 1-BP concentrations in
dosing formulations were similar to
target concentrations, but 1-BP
concentrations measured in
preincubation solutions were shown to
be far below target concentrations. At 0
minutes in the confirmatory
mutagenicity assays, 1-BP
concentrations in preincubation tubes at
the highest target level (5000 ng/plate)
were 4% to 9% of target, which
corresponds to 1-BP concentrations of
200-450 ng/plate; by the end of the 90-
minute preincubation exposure period,
measured 1-BP concentrations at the
highest target level (5000 |ig/plate) were
2% to 3% of target, which corresponds
to 1-BP concentrations of approximately
100-150 ng/plate. No analysis of 1-BP
concentrations was conducted at the end
of the plate incubation period (after 48-
72 hours), but negligible 1-BP
concentrations would be expected since
OECD TG 471 indicates that the
test report must include specific
types of information, including
purity of the test substance.
Given the volatility of 1-BP, it
may be especially important to
verily concentrations of the test
substance as a 'special case'.
Page 476 of 486
-------
Metric
Barber et al. (1981)
BioReliance (2015)
OECD (1997)
no volatility control was used during the
plate incubation period.
Methods
reporting
details
provided
Not orovidcd: Bacterial
titers (cells/mL); raw data
(i.e., individual plate
counts); revertants/plate data
for the two strains in which
no mutagenicity was
observed (i.e., S.
typhimurium strains TA
1537 and TA 1538);
standard deviations for
mean numbers of
revertants/plate (except
positive and negative
controls); historical control
data.
Negative control results
were noted to have been in
good agreement with those
found in an interlaboratory
survey (De Serres and
Shelbv. 1979) and those
presented by Ames et al.
(1975).
Not orovidcd: None (items
recommended by OECD TG 471 were
reported)
The guideline indicates a
number of items that must be
included in the test report (with
respect to the test substance,
solvent/vehicle, strains, test
conditions, and results).
Closed-
system
protocol
details
Svstem used: Modified
plate-incorporation test.
Pyrex containers with
circular Teflon tops (drilled
and threaded to
accommodate valve and
septum assemblies and
containing a sampling port);
containers accommodated a
metal rack holding up to 12
glass plates. An O-ring was
used to ensure a good seal
between the container and
the top; clamps were used to
hold tops in place.
Addition of 1-BP: Under a
hood, prepared plates (with
or without activation) were
introduced to the Pyrex
containers. A plate
containing sterile, distilled
water (30 mL) was added to
each container for GLC
analysis of 1-BP
System: Preincubation method. Screw-
capped tubes during preincubation;
minimal head space documented for the
second confirmatory mutagenicity assay
only.
Addition of 1-BP: Dosins formulations
of 1-BP were prepared in screw-capped
tubes with minimal headspace; use of
minimal headspace was documented
only for the second of two confirmatory
assays. To prepare preincubation
solutions, 1-BP dosing formulations or
vehicle (ethanol), S9 or sham mix, and
the tester bacterial strain were added to
glass culture tubes preheated to
37±2LC. Tubes containing 1-BP were
capped using screw caps (amount of
headspace not reported) during the
preincubation period (90 minutes at
37°C). Following preincubation, top
agar was added, and the mixture was
overlaid onto minimal bottom agar.
Once solidified, plates were inverted and
OECD TG 471 indicates that
certain classes of mutagens
(including gases and volatile
chemicals) are not always
detected using standard
procedures such as the plate
incorporation or preincubation
methods; therefore, these are
considered 'special cases' and
alternative procedures
(scientifically justified) should
be used for their detection.
Gases or volatile substances
should be tested by appropriate
methods, such as in sealed
vessels.
Page 477 of 486
-------
Metric
Barber et al. (1981)
BioReliance (2015)
OECD (1997)
concentrations at the end of
the exposure period. After
sealing the containers and
drawing a partial vacuum, 1-
BP was added through the
septum using a syringe.
Once the liquid vaporized
(ascertained visually), air
was added via the valve
until the pressure inside the
containers was equal to
ambient pressure.
Containers were removed
from the hood and incubated
for 48 hours at 37°C (with
continuous stirring of the
atmosphere in each
container).
placed in desiccators by dose level for
48 to 72 hours at 37°C.
Activation
system
Aroclor-induced rat liver S9
The concentration of S9 in
S9 mix was not reported.
For plates with metabolic
activation, top agar
contained 0.2 mL overnight
culture, 2.0 mL agar, and
0.5 mL S9 mix.
Aroclor 1254-induced rat liver S9 (male
Sprague-Dawley rats)
The S9 mix contained a final S9
concentration of 10% v/v. Preincubation
tubes contained 0.5 mL S9 or sham mix,
100 |iL tester strain, and 25 |iL vehicle
or test substance dilution, to which 2.0
mL agar was added after the 90-minute
preincubation period.
Bacteria should be exposed to
the test substance in the presence
and absence of an appropriate
metabolic activation system. The
most commonly used system is a
cofactor-supplemented post-
mitochondrial fraction (S9)
prepared from the livers of
rodents treated with enzyme-
inducing agents such as Aroclor
1254 or a combination of
phenobarbitone and (3-
naphthoflavone. The post-
mitochondrial fraction is usually
used at concentrations in the
range from 5 to 30% v/v in the
S9 mix. Usually, 0.05 or 0.1 mL
of test substance/solution, 0.1
mL bacteria, and 0.5 mL S9 mix
or sterile buffer are mixed with
2.0 mL of top agar.
Bacterial
strains
S. typhimurium strains TA
98, TA 100, TA 1535, TA
1537, and TA 1538
This combination of strains
conforms to the guideline
except that TA 1538 was
used in lieu of E coli WP2
uvrA or E. coli WP2 uvrA
(pKMlOl) orS.
typhimurium TA 102. The
test plates were prepared
S. typhimurium strains TA 98, TA 100,
TA 1535, and TA 1537; E. coli strain
WP2 uvrA
This combination of strains conforms to
the guideline. To assure that cultures
were harvested in the late log phase, the
length of incubation was controlled and
monitored. Each culture was monitored
spectrophotometrically for turbidity and
harvested at a percent transmittance
yielding a titer > 0.3 x 109 cells/mL.
Fresh cultures grown up to the
late exponential or early
stationary phases of growth
should be used (approximately
109 cells/mL; not late
stationary). At least 5 strains of
bacteria should be used. These
should include 4 strains of S.
typhimurium (TA 1535, TA
1537 or TA 97a or TA 97, TA
98, and TA 100). These strains
have GC base pairs at the
Page 478 of 486
-------
Metric
Barber et al. (1981)
BioReliance (2015)
OECD (1997)
from overnight growth
cultures (phase of growth
not reported); the number of
cells/mL was not specified.
Actual titers were determined by viable
counts assays (actual counts were 1.3 to
5.7 x 109 cells/mL).
primary reversion site and may
not detect certain oxidizing
mutagens, cross-linking agents,
and hydrazines. Such substances
may be detected using E. coli
WP2 strains or S. tvphimurium
TA 102, which have an AT base
pair at the primary reversion site.
To detect cross-linking
mutagens, it may be preferable
to include TA 102 or a DNA
repair-deficient strain of E. coli,
such as WP2 or WP2 (pKMlOl).
The guideline specifies a
recommended combination of
strains (S. tvphimurium TA
1535; S. tvphimurium TA 1537
or TA 97a or TA 97; S.
tvphimurium TA 98; S.
tvphimurium TA 100; and E. coli
WP2 uvrA or E. coli WP2 uvrA
(pKMlOl) or S. tvphimurium TA
102).
Duration
of
exposure
48 hours at 37LC
90±2 minutes at 37±2°C (preincubation
period with test article or controls); 48-
72 hours at 371C (plate incubation
period)
For the preincubation method,
cultures should be incubated for
20 minutes or more at 30-37°C
prior to mixing with top agar.
All plates should be incubated at
37°C for 48 to 72 hours.
Time
of
assessment
Number of revertant
colonies/plate was counted
after 48 hours incubation
Number of revertant colonies counted
after 48-72 hours incubation (plates that
were not counted immediately were
stored at 2-81C)
All plates should be incubated at
37°C for 48 to 72 hours. After
the incubation period, the
number of revertant colonies per
plate is counted.
Type
of
assessment
Revertant colonies counted
using a colony counter.
Criteria for a Dositive result:
Increased revertants/plate
compared to controls;
statistical analysis
(Student's t-test tables) was
used to determine the
minimum vapor
concentration that
significantly increased the
number of revertant
colonies.
Revertant colonies counted either
entirely by automated colony counter or
entirely by hand (except positive
controls).
Criteria for a positive result: Dose-
related increases in the numbers of
revertants/plate in at least one strain over
a minimum of two increasing
concentrations of 1-BP; at least 3-fold
increase in revertants for S. tvphimurium
strains TA 1535 and 1537 and at least 2-
fold increases for all other strains.
After the incubation period, the
number of revertant colonies per
plate is counted (method of
counting not specified). Criteria
for determining a positive result
include a concentration-related
increase over the range tested
and/or a reproducible increase at
one or more concentrations in at
least one strain with or without
activation. Biological relevance
should be considered first;
statistical methods may be used
but should not be the only
determining factor. Any result
that does not meet these criteria
is considered negative. Data
Page 479 of 486
-------
Metric
Barber et al. (1981)
BioReliance (2015)
OECD (1997)
should be presented as the mean
number of revertant colonies per
plate and standard deviation.
There is no requirement for
verification of a clear positive
result. Equivocal results should
be clarified by modifying
experimental conditions,
whenever possible. Negative
results need to be confirmed on a
case-by-case basis; if not
confirmed, justification should
be provided.
GLC = gas-liquid chromatography; GC = gas chromatography
J.5.8 Metabolism, Structure-Activity Relationships and Mechanism/Mode of
Action
Studies in experimental animals and humans indicate that 1-BP can be absorbed following
inhalation, oral, or dermal exposure (Cheever et al.. 2009; NIOSH. 2007). Metabolism studies
show that oxidation by P450 enzymes (e.g., CYP2E1) and glutathione conjugation are the primary
metabolic pathways (Garner et al.. 2006; Ishidao et al.. 2002). Over 20 metabolites have been
identified in rodent studies, including the four metabolites that can be detected in urine samples of
workers exposed to 1-BP (Hanlev et al.. 2009). Besides being a direct-acting alkylating agent, 1-
BP may be converted to either of two epoxide metabolites, glycidol and propylene oxide, by
oxidation followed by cyclization of the resulting alpha-bromohydrin intermediates. Both the 2-
and 3- positions on 1-bromopropane are susceptible to oxidation by cytochrome P450 (NTP.
2013b). Oxidation at the 3-position results in the formation of 3-bromo-l-propanol. Further
oxidation of this intermediate at the 2-position yields 3-bromo-l,2-propanediol, which can cyclize
to form glycidol. Propylene oxide may be formed by a similar, though shorter pathway. Oxidation
of 1-bromopropane at the 2-position yields l-bromo-2-propanol. This bromohydrin intermediate
may then be cyclized to form propylene oxide. Glycidol was detected in urine of rats exposed 6
hours/day to 1-BP by inhalation for 3 to 12 weeks (Ishidao et al.. 2002). Metabolic pathways by
which propylene oxide may be generated from 1-BP are shown in Jones and Walsh (1979). NTP
(2013b). and IARC (2018) and a pathway by which glycidol may be generated from 1-BP is shown
in IARC (2018). Epoxide intermediates such as propylene oxide and glycidol are expected to have
more mutagenic activity than 1-BP (IARC. 2018. 2000. 1994).
Mice appear to have a greater capacity to oxidize 1-BP than rats (Garner et al.. 2006). This species
difference in metabolic capacity may explain why mice were found to be more sensitive to 1-BP
toxicity than rats. The identified or putative reactive intermediates for 1-BP include the epoxides
noted above (glycidol, and propylene oxide), a-bromohydrin and 2-oxo-l-BP (NTP. 2014; Ishidao
et al.. 2002; Mitchell et al.. 1998). Detoxification of 1-BP metabolites occurs primarily via
glutathione-S-transferase (GST) -mediated conjugation with glutathione (NTP. 2014; Liu et al..
2009; Garner et al.. 2006).
Page 480 of 486
-------
1-BP is expected to be a good alkylating agent because bromine is a good leaving group. Two of
its closest homologs, bromoethane and 1-bromobutane, were both shown to be mutagenic in the
Ames Salmonella test; in both cases, use of desiccators was needed to show positive results (NTP.
1989b; Simmon et al.. 1977). Bromoethane is a known carcinogen via the inhalation route of
exposure (NTP. 1989b). whereas 1-bromobutane has not been tested for carcinogenic activity. 1-
BP is a relatively soft electrophile which is expected to preferentially react with sulfhydryl (-SH)
residues on glutathione and proteins before binding to DNA. Besides being a direct-acting
alkylating agent, 1-BP may be metabolically activated to genotoxic intermediates (see above). A
number of other structurally-related halogenated alkanes such as 1,2-dibromoethane (ethylene
dibromide) (IARC. 1999e). dichloromethane (IARC. 1999d). 1,2-dichloroethane (IARC. 1999b).
l,2-dibromo-3-chloropropane (IARC. 1999a) and 1,2,3-trichloropropane (IARC. 1999c) have been
classified as "probably carcinogenic to humans (group 2A)" or "possibly carcinogenic to human
carcinogens" (group 2B) by the International Agency for Research on Cancer; however, some of
these chemicals may have different mechanisms.
The mechanism/mode of action for 1-BP carcinogenesis is not clearly understood. More research is
needed to identify key molecular events. Since 1-BP can induce tumors in multiple organs and can
act directly as an alkylating agent, as well as indirectly via metabolically-activated reactive
intermediates such as glycidol and propylene oxide, it may have different mechanisms in different
target organs. Whereas the reasonably available data/information and the weight of the scientific
evidence provide some support for a MMOA for 1-BP carcinogenesis, at least three additional
mechanisms, oxidative stress, immunosuppression, and cell proliferation may contribute to the
multi-stage process of carcinogenesis (NTP. 2013b).
As discussed in the previous section on genotoxicity, 1-BP and its genotoxic reactive intermediates
can induce DNA mutations and/or chromosome aberrations. Although the results are not as clear
cut for 1-BP itself, some of the discrepancies may be explained by testing limitations. Available
structure-activity relationship analyses support the genotoxic potential of 1-BP. The induction of
tumors in multiple targets by 1-BP is also a common characteristic of genotoxic carcinogens. DNA
binding studies show formation of N7-propyl guanine adducts by 1-BP, although these specific
adducts are not known to result in mutations. Overall, the weight of scientific evidence for a
MMOA for 1-BP carcinogenesis is suggestive but inconclusive.
Oxidative stress due to cellular glutathione depletion could contribute to the carcinogenicity of 1-
BP (Morgan et al.. 2011). Oxidative stress is an important epigenetic mechanism that can
contribute to all three stages of carcinogenesis - oxidation can induce initiation (as a result of DNA
damage), promotion (as a result of compensatory cell proliferation in response to cell necrosis),
and progression (via oxidative changes in signal transduction and gene expression; rev. (Woo and
Lai. 2003). Exposure to 1-BP has also been shown to deplete glutathione in various tissues (e.g.,
(Liu et al.. 2009; Lee et al.. 2007; Wang et al.. 2003). which can lead to a loss of protection against
electrophiles.
As summarized in the previous section on genotoxicity, 1-BP did not induce mutations at the ell
gene of female B6C3F1 transgenic Big Blue® mice following whole-body inhalation exposures to
Page 481 of 486
-------
1-BP vapor concentrations of 62.5, 125, or 250 ppm 5 days/week for 28 days (Stellies et al.. 2019;
Weinberg. 2016); or 7 days/week for 28 days (Young. 2016). The guideline for transgenic rodent
somatic and germ cell gene mutation assays (OECD. 2013) indicates that daily exposures to test
substance are needed in a repeated-dose protocol of at least 28 days based on "observations that
mutations accumulate with each treatment." Thus, the 5 days/week exposure protocol (Stellies et
al.. 2019); Weinberg, (2016) was deficient, but the 7 days/week exposure protocol of Young
(2016) conformed to the (OECD. 2013) guidance to use daily exposures to test substance.
Due to the following issues, the negative Big Blue® rodent mutation assays in female B6C3F1
mice (Stellies et al.. 2019); Weinberg. 2016; Young, (2016) do not provide definitive evidence
against a MMOA of 1-BP carcinogenicity:
(a) The study protocol was not optimal for detection of mutations because the highest test
concentration of 250 ppm was not a Maximum Tolerated Dose (MTD). The MTD is
defined as the dose producing signs of toxicity such that higher dose levels, based on the
same dosing regimen, would be expected to produce lethality (OECD. 2013). Given that
there were no treatment-related effects on survival, clinical observations, body weights,
food consumption, or organ weights, the highest 1-BP test concentration was not an MTD
and the study needs to be repeated to include a top concentration at the MTD.
(b) The studies assessed only females, but it is possible that males may also be sensitive to
mutagenicity/carcinogenicity from exposure to 1-BP. Indeed, the NTP (2011b) 2-year
inhalation study found statistically-significant increases in tumor incidence not only in
female B6C3F1 mice but also in both male and female F344/N rats.
(c) The studies assessed only mice, at a maximum 1-BP exposure concentration of 250 ppm,
but the 3-month toxicity studies that preceded the NTP 2-year bioassay showed that F344/N
rats tolerated a higher repeated-dose inhalation concentration (500 ppm) than B6C3F1 mice
(250 ppm). Thus, to provide higher sensitivity for detection of potential mutagenicity in
rodents, an additional in vivo mutation assay using Big Blue® F344/N rats could be
conducted using a higher maximum inhalation concentration than that used in the mouse
study, i.e., 500 ppm should be part of the range tested in Big Blue® F344/N rats. According
to (OECD. 2013). "the use of transgenic rat models should be considered," for example,
"when investigating the mechanism of carcinogenesis for a tumor seen only in rats." The
NTP (2011b) 2-year bioassay of 1-BP reported that neoplasms of skin (in both sexes), large
intestines (in females), and pancreas (in males) as well as increased incidences of malignant
mesotheliomas (in males) occurred only in F344/N rats, which provides additional
justification for 1-BP mutagenicity testing in Big Blue® F344/N rats of both sexes.
(d) The Big Blue® assay typically evaluates fast and slow mutation fixation/repairing tissue
types. The 1-BP studies assessed mutagenicity only in lung, liver and colon but, because of
differences in metabolic enzymes/cytochrome p450s among mammalian organs and tissues
and different species, several tissues of rats and mice should be sampled for mutations in
the Big Blue® rodent mutagenicity assay of 1-BP to minimize the possibility of false
negative mutagenicity results. The NTP (2011b) 2-year study for 1-BP included neoplasm
findings for skin, large intestines, lung, and pancreas. Before concluding that a MMOA of
1-BP is not operable for all target sites, additional target sites, including skin, pancreas, and
Page 482 of 486
-------
intestines at a minimum, would need to be assessed for 1-BP in Big Blue® models for both
B6C3F1 mice and F344/N rats.
(e) Test chemical exposures of longer than 28 days may be needed for "detecting mutations in
slowly proliferating organs" (OECD. 2013). Further research may be needed to determine if
1-BP exposure periods of more than 28 days are needed for detection of potential mutations
in the Big Blue® assay.
(f) The Big Blue® rodent assay may fail to detect mutagens if the post-exposure fixation time
is too short to allow fixing of DNA damage into stable mutations. Likewise, the assay can
fail to detect mutagens if a rapid cell turnover in a particular tissue, together with longer
post-exposure time, decrease the frequency of cells that carry mutations in reporter genes.
As indicated in (OECD. 2013) administration of the test agent "is usually followed by a
period of time, prior to sacrifice, during which the agent is not administered and during
which unrepaired DNA lesions are fixed into stable mutations. In the literature, this period
has been variously referred to as the manifestation time, fixation time, or expression time."
In the Big Blue® mouse studies of 1-BP, the post-exposure fixation time was 3 days, which
may provide adequate sensitivity for detection of mutagenicity in some tissues but not
others. (OECD. 2013) recognizes the issue of potential underestimation of mutagenic
potential, noting that the fixation period is tissue-specific and that "maximum mutant
frequency may not manifest itself in slowly proliferating tissues" when a 3-day fixation
period is used. To address the possibility of underreporting mutagenic potential for slowly
proliferating tissues, (OECD. 2013) indicates that "a later sampling time of 28 days
following the 28 day administration period may be more appropriate." Further research is
needed on the lengths of fixation periods needed to manifest mutagenicity in each tissue
sampled in future Big Blue® rodent assays of 1-BP.
(g) The Big Blue® assay lacks a body of data on mutagenic and carcinogenic chemicals with
structural similarity to 1-BP. One of the closest homologs of 1-BP, bromoethane, is positive
in closed-system testing in the Ames Salmonella mutagenicity assay (NTP. 1989b; Simmon
et al.. 1977) and is carcinogenic by the inhalation route (NTP. 1989b). To enhance
confidence that the methods used for 1-BP testing in the Big Blue® assays are sufficient to
prevent false negative mutagenicity findings, mutagenicity data from Big Blue® assays of
rats and mice are needed from independent testing of bromoethane (and other known
mutagenic carcinogens with structural similarity to 1-BP) or these 1-BP analogs could be
included as potentially-positive controls in additional Big Blue® studies of 1-BP. If
mutagenic and carcinogenic structural analogs of 1-BP are not mutagenic in Big Blue®
rodent assays, it can be concluded that these assays are not suitable for assessing the
mutagenicity of 1-BP.
Besides genotoxicity and oxidative stress, 1-BP has been shown to cause immunosuppression in
rodents (Anderson et al.. 2010; Lee et al.. 2007). Immunosuppression can facilitate tumor
progression by lowering the immunosurveillance process against tumor growth. There is also some
evidence that 1-BP can cause y-aminobutyric acid (GABA) dysfunction and thereby impact cell
proliferation, differentiation and migration of neuronal cells (NTP. 2013a).
Page 483 of 486
-------
Several known or proposed metabolites of 1-BP have been shown to be mutagenic CNTP. 2014;
I ARC. 2000. 1994). For example, both glycidol and propylene oxide are mutagenic in bacteria,
yeast, Drosophila, and mammalian cells. These compounds have also been shown to induce DNA
and chromosomal damage in rodent and human cells, and can form DNA adducts in vitro.
a-Bromohydrin and 3-bromo-l-propanol were mutagenic in the S. typhimurium reversion assay,
and 3-bromo-l-propanol and l-bromo-2-propanol induced DNA damage in E. coli. The available
in vivo test results for glycidol indicate that it induces micronucleus formation, but not
chromosomal aberrations in mice. Studies of propylene oxide indicated chromosomal damage
evidenced by positive responses for micronucleus induction in mouse bone marrow and
chromosomal aberration tests; DNA damage was evident in the sister chromatid exchange (SCE)
assay.
Page 484 of 486
-------
Appendix K 1-BP: Mutagenic Mode of Action Analysis
According to the Cancer Guidelines and the Supplemental Guidance for Assessing Susceptibility
from Early Life Exposure to Carcinogens (U.S. EPA. 2005a. b), individuals exposed during early
life stages {i.e., development) to carcinogens with a MMQA are assumed to have an increased risk
for cancer. The framework for the weight of the scientific evidence for mutagenicity is used to
consider the available data (U.S. EPA. 2005a). Age-Dependent Adjustment Factors (ADAFs) are
then applied for carcinogens with a MMOA and/or for carcinogens with available data indicating
increased susceptibility after developmental life stage exposure (U.S. EPA. 2005b) if relevant to
potentially exposed populations.
According to the Supplemental Guidance for Assessing Susceptibility from Early Life Exposure to
Carcinogens ((U.S. EPA. 2005b); see Figure_Apx K-l below), chemicals are considered for
whether there is a MMOA in animal studies. This figure illustrates the considerations and decision
logic for whether ADAFs are applied. For 1-BP, the data are suggestive of a MMOA, but not
conclusive. Therefore, linear extrapolation was performed as default and ADAFs were not applied.
MOA sufficiently
supported in animals?
MOA cannot be determined
I
YES
MOA relevant to
humans?
NO
I
YES
Flag Hfestage or population that
could be susceptible based on
information about the specific MOA
for dose response analysis.
I
Determine extrapolation
based on information about
specific MOA.
Linear, but not mutagenic
I
Linearity due to mutagenic MOA
Were chemical-specific data available in MOA
analysis to evaluate differences between adults and
juveniles (more, less, or the same susceptibility)'7
YES
I
Eariy-life susceptibility assumed. Apply age
dependent adjustment factors (ADAFs) as
appropriate to develop risk estimates.
Use linear extrapolation
as default
No further analysis of
Model using MOA or use
RfD/RfC method as default.
Adjustments for susceptible
lifestages or populations are
part o f the process.
Use the same linear
extrapolation for all lifestages,
unless have chemical specific
information on lifestages or
populations
Develop chemical-specific risk
estimates incorporating
lifestage susceptibility
Figure Apx K-l. 1-BP Mutagenic MOA Weight of the Scientific Evidence Determination
Following the Supplemental Guidancel for Assessing Susceptibility from Early-Life
Exposure to Carcinogens
Page 485 of 486
-------
1 EPA's Guidelines for Carcinogen Risk Assessment (U.S. EPA. 2005a) includes a framework to establish MOA(s) for
a chemical. Purple boxes indicate the decisions made for 1-BP based on the available animal and human cancer studies
and mechanistic studies. Blue boxes indicate options in the supplemental guidance that were not supported by the
available 1-BP data. The WOE for 1-BP for a mutagenic MOA is suggestive but inconclusive. This figure was adapted
from Figure 1-1. Flow chart for early-life risk assessment using mode of action framework in the Supplemental
guidance (U.S. EPA. 2005b).
TableApx K-l. Decisions and Justification Relating to Mutagenic Mode of Action Analysis
for 1-BP (see Figure 1 from (U.S. EPA, 2005b)
Decision
Justification
Document; p. #
MOA not sufficiently
supported in animals
WOE for MMOA is suggestive but inconclusive.
Section 3.2.4.2
There are uncertainties in the 1-BP database associated with a hypothesized MMOA for
carcinogenesis. Data gaps include conclusive information on the mutagenic properties of 1-BP and
its metabolites in vitro and in vivo, data on the nature and frequencies of mutations in workers
exposed to 1-BP over time, information on variations in susceptibility of the human population to
cancer (e.g., related to cyp2El polymorphisms or other differences), and associations between
developmental life stage exposure and cancer in childhood and adulthood. The available data are
not sufficient to establish the molecular initiating and/or key events in the adverse outcome
pathway from 1-BP exposure to development of cancer.
Page 486 of 486
------- |