TSCA Workplan Chemical Risk Assessment of NMP

DRAFT DO NOT CITE OR QUOTE
United States
Environmental Protection
Agency
Office of Chemical
Safety and Pollution
Prevention
TSCA Workplan Chemical Risk Assessment

N-Methylpyrrolidone:
Paint Stripping Use
CASRN: 872-50-4
December 2012
NOTICE
This document is an External Review Draft. This information is distributed solely for the
purpose of pre-dissemination peer review under applicable information quality guidelines. It
has not been formally disseminated by EPA. It does not represent and should not be construed
to represent any Agency determination or policy. It is being circulated for review of its
technical accuracy and science policy implications.
Page 1
Table of Contents
AUTHORS / CONTRIBUTORS / ACKNOWLEDGEMENTS / REVIEWERS ...................................... 8
GLOSSARY OF TERMS AND ABBREVIATIONS........................................................................... 9
EXECUTIVE SUMMARY ......................................................................................................... 12
CHAPTER 1: BACKGROUND AND SCOPE............................................................................... 14
INTRODUCTION ............................................................................................................................................................. 14
SCOPE OF THE ASSESSMENT ............................................................................................................................................ 15
CHAPTER 2: SOURCES AND ENVIRONMENTAL FATE ............................................................. 17

INTRODUCTION ............................................................................................................................................................. 17
2.1. CHEMICAL AND PHYSICAL PROPERTIES ....................................................................................................................... 17
2.2. PRODUCTION VOLUME AND USES ............................................................................................................................. 18
2.2.1. Consumer Uses .......................................................................................................................................... 19
2.2.2. Paint Stripping Applications ...................................................................................................................... 19
2.3. CONCLUSIONS ON PRODUCTION VOLUME AND USES ..................................................................................................... 20
2.4. ENVIRONMENTAL FATE ........................................................................................................................................... 20
2.4.1. Fate in Air .................................................................................................................................................. 20
2.4.2. Fate in Water ............................................................................................................................................ 20
2.4.3. Fate in Soil and Sediment .......................................................................................................................... 21
2.4.4. Bioconcentration and Persistence ............................................................................................................. 21
2.5. CONCLUSIONS OF ENVIRONMENTAL FATE ................................................................................................................... 22
CHAPTER 3: HUMAN HEALTH RISK ASSESSMENT ................................................................. 23

INTRODUCTION ............................................................................................................................................................. 23
3.1. HUMAN EXPOSURE ASSESSMENT .............................................................................................................................. 23
3.1.1. Occupational Exposures ............................................................................................................................ 23
3.1.2. Background and Context of Paint-Stripping Industry ................................................................................ 24
3.1.3. Occupational Dermal Exposure Assessment ............................................................................................. 26
3.1.4. Occupational Inhalation Exposure Assessment......................................................................................... 27
3.1.5. Residential Exposure Assessment ............................................................................................................. 28
3.1.6. Residential Dermal Exposure Assessment ................................................................................................. 28
3.1.7. Residential Inhalation Exposure Assessment ............................................................................................ 30
3.2. HUMAN HEALTH ASSESSMENT ................................................................................................................................. 44
3.2.1. TOXICOKINETICS ........................................................................................................................................... 45
3.2.2. Hazard Identification................................................................................................................................. 46
3.2.3. Dose-Response Assessment ...................................................................................................................... 47
3.2.4. Key Studies, PODs, and Levels of Concern for the Dermal Pathway.......................................................... 48
3.2.5. Key Studies, PODs, and Levels of Concern for the Inhalation Pathway ..................................................... 49
3.3. HUMAN HEALTH RISK CHARACTERIZATION ................................................................................................................. 51
3.3.1. Risk Estimation Approach for Acute and Chronic Exposures ..................................................................... 52
3.3.2. Risk Estimates for Non-Cancer Acute Dermal Exposures in a Residential Setting..................................... 54
3.3.3. Risk Estimates for Non-Cancer Acute Inhalation Exposures in a Residential Setting ................................ 54
3.3.4. Risk Estimates for Non-Cancer Chronic Dermal Exposures to Workers..................................................... 57
3.3.5. Risk Estimates for Non-Cancer Chronic Inhalation Exposures to Workers ................................................ 57
3.4. DISCUSSION OF KEY SOURCES OF UNCERTAINTY AND DATA LIMITATIONS ......................................................................... 58
3.4.1. Key Uncertainties and Data Limitations for Occupational Exposure Estimates ........................................ 58
3.4.2. Uncertainties in the Residential Exposure Assessment ............................................................................. 59
3.4.3. Uncertainties in the Hazard- and Dose-Response Assessments ................................................................ 61
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3.5. RISK ASSESSMENT CONCLUSIONS .............................................................................................................................. 64
REFERENCES ........................................................................................................................ 65
APPENDIX A. ENVIRONMENTAL EFFECTS SUMMARY ........................................................... 78
APPENDIX B. BIOMONITORING DATA ................................................................................. 80
APPENDIX C. OCCUPATIONAL EXPOSURE ASSESSMENT SUPPORT INFORMATION ................ 81
DERIVATION OF NMP CONCENTRATION CONVERSION FACTOR FOR OCCUPATIONAL EXPOSURE CALCULATIONS .............................. 81
DESCRIPTIONS OF OCCUPATIONAL PROCESSES AND ACTIVITIES............................................................................................... 82
FACILITY AND POPULATION DATA .................................................................................................................................... 86
OCCUPATIONAL INHALATION EXPOSURE LITERATURE DATA ................................................................................................... 90
DERMAL EXPOSURE MODELING ....................................................................................................................................... 93
APPENDIX D. CONSUMER EXPOSURE ASSESSMENT ............................................................. 95

ESTIMATION OF EMISSION PROFILES FOR PAINT REMOVERS/STRIPPERS ................................................................................... 95
SENSITIVITY ANALYSIS FOR INHALATION SCENARIOS ........................................................................................................... 103
INHALATION EXPOSURE SCENARIO INPUTS ....................................................................................................................... 103
INHALATION MODEL OUTPUTS AND EXPOSURE CALCULATIONS ............................................................................................ 111
MCCEM INHALATION MODELING CASE SUMMARIES ........................................................................................................ 118
DERMAL ASSESSMENT INPUTS ....................................................................................................................................... 142
APPENDIX E. TOXICOLOGY STUDIES .................................................................................. 145

INHALATION TOXICITY STUDIES ...................................................................................................................................... 145
DERMAL TOXICITY STUDIES ........................................................................................................................................... 148
IRRITATION, SENSITIZATION, AND CANCER ....................................................................................................................... 149
APPENDIX F. BMD ANALYSIS OF SAILLENFAIT ET AL. (2003) DATA...................................... 150

APPENDIX G. EPAS EVALUATION OF THE POET ET AL. (2012) PBPK MODEL FOR NMP ....... 154
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List of Tables
Table 2-1. Physical-Chemical Properties of NMP......................................................................... 17
Table 2-2. NMP Production Volume Information. ..................................................................... 18
Table 2-3. Consumer Uses of NMP. ............................................................................................. 19
Table 2-4. Environmental Fate Characteristics of NMPa.............................................................. 22
Table 3-1. 2007 NAICS Codes Identified that Include Paint Stripping Activities. ......................... 24
Table 3-2. Summary of Worker Dermal Model Parameters and Resultsa. ................................... 26
Table 3-3. Summary of Ranges of NMP Inhalation Exposures and Calculated ADCs for Workers.
................................................................................................................................... 28
Table 3-4. Estimated Consumer Dermal Exposure Results. ......................................................... 30
Table 3-5. NMP Exposure Scenarios for the Characterizing Consumer Inhalation Exposure. .... 37
Table 3-6. NMP Consumer Paint Stripping Scenario Descriptions and Parameters..................... 39
Table 3-7. Summary of Modeled NMP Concentrations to Which Consumer Users and Non-Users
are Exposed, by Scenario. .......................................................................................... 42
Table 3-8. Summary of Exposure Pathways, Toxic Endpoints and Risk Approach. ...................... 44
Table 3-9. Time Scaling of Chronic POD Values. ........................................................................... 51
Table 3-10. Dose-Response Values and Risk Approaches for NMPs Human Health Risk
Assessment. ............................................................................................................... 53
Table 3-11. Acute MOEs for Residential Users and Non-Users of NMP-Based Paint Strippers
Dermal Exposures. ..................................................................................................... 54
Table 3-12. Acute MOEs for Residential Users and Non-Users of NMP-Based Paint Strippers
Inhalation Exposures. ................................................................................................ 56
Table 3-13. Chronic MOEs for Worker Dermal Exposures............................................................ 57
Table 3-14. Chronic MOEs for Worker Inhalation Exposures. ...................................................... 58
Table A-1. Summary Table for Aquatic Toxicity Data of NMP ...................................................... 78
Table C-1. 2007 US Economic Census Data for Painting and Wall Covering and Flooring
Contractors. ............................................................................................................... 86
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Table C-2. 2007 US Economic Census Data for Automotive Body, Paint, and Interior Repair and
Maintenance. ............................................................................................................. 87
Table C-3. 2007 US Economic Census Data for Reupholstery and Furniture Repair. ................... 87
Table C-4. 2007 US Economic Census Data for Industry Sectors that May Engage in Art
Restoration and Conservation Activities. .................................................................. 88
Table C-5. 2007 US Economic Census Data for Aircraft Manufacturing. ..................................... 88
Table C-6. 2007 US Economic Census Data for Ship Building and Repairing................................ 89
Table D-1. MRI Studies: Products Emissions Fit to Exponential Profile. ...................................... 95
Table D-2. Fitted Parameters to the US EPA (1994b) Study Results for the Two DCM-Containing
Paint Strippers. .......................................................................................................... 98
Table D-3. Fitted Parameters to the US EPA (1994b) Study Results for Wood Finishers Pride.
................................................................................................................................. 101
Table D-4. Time Schedule for Paint Stripping with Repeat Application. ................................... 105
Table D-5. NMP Mass Released, by Application Target and Method. ....................................... 106
Table D-6. Literature-Reported Vapor Pressure Values for NMP. ............................................. 109
Table D-7. Dermal Modeling Scenarios...................................................................................... 142
Table D-8. Summary of Dermal Input Parameters. ................................................................... 142
Table F-1. Fetal body weight data from pregnant Sprague-Dawley rats exposed to NMP from
GD 6-20.a ................................................................................................................. 150
Table F-2. Summary of dose-response analysis and point of departure estimation for fetal body
weight from pregnant Sprague-Dawley rats exposed to NMP from GD 6-20. ....... 150
Table G-1. Comparison of average daily plasma NMP AUCs from Poet et al. 2012 (Tables 3 and
4) and present (10/16/12) simulations of rat inhalation repro/developmental
bioassays, using study-specific body weights.......................................................... 158
Table G-2. Comparison of rat internal dose BMC values and HECs from Poet et al. (2012) and
present simulations ................................................................................................. 164
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List of Figures
Figure 2-1. Chemical Structure of NMP. ....................................................................................... 17
Figure 3-1. Time-varying Consumer User Personal Concentration and Maximum TWA Values for
Selected Averaging Times. ......................................................................................... 34
Figure 3-2. Time-varying Consumer Non-user Personal Concentration and Maximum TWA
Values for Selected Averaging Times......................................................................... 34
Figure 3-3. Model Sensitivity Results (Percent Change from Base-case Response) for Peak Onehr TWA for Consumer User and Non-user................................................................. 36
Figure 3-4. Model Sensitivity Results (Percent Change from Base-case Response) for 24-hr TWA
for Consumer User and Non-user.............................................................................. 36
Figure C-1. Typical Flow Tray for Applying Stripper to Furniture (IRTA, 2006). ........................... 84
Figure C-2. Typical Water Wash Booth Used to Wash Stripper and Coating Residue from
Furniture (IRTA, 2006). .............................................................................................. 84
Figure C-3. Example Diagram of a Dipping Tank for Furniture Stripping (HSE, 2001). ................. 85
Figure D-1. Model Fit to MRI (US EPA, 1994b) Data for BIX Spray-On (Spray Application). ....... 97
Figure D-2. Model Fit to MRI (US EPA, 1994b) Data for Strypeeze (Brush Application). ............ 98
Figure D-3. Theoretical Cumulative Mass of DCM Released for BIX Spray-On Stripper.............. 99
Figure D-4. Theoretical Cumulative Mass of DCM Released for Strypeeze Stripper................... 99
Figure D-5. Model Fit to MRI (US EPA, 1994b) Data for Wood Finishers Pride (Brush
Application).............................................................................................................. 101
Figure D-6. Theoretical Cumulative Mass of NMP Released from Wood Finishers Pride. ....... 102
Figure D-7. Zone Volumes and Airflow Rates for Workshop Scenarios..................................... 108
Figure D-8. Zone Volumes and Airflow Rates for Bathroom Scenario....................................... 108
Figure D-9. Example of the Personal Concentration Calculation as Defined in Equation C-13. 112
Figure D-10. Modeled NMP Concentrations for Scenarios 1 and 4, Stripper Application in
Workshop using Parameter Values selected for Central Tendency Exposure. ....... 114
Figure D-11. Modeled NMP Concentrations for Scenarios 2 and 5, Stripper Application in
Workshop using Parameter Values selected for Upper-end User Exposure. ......... 115
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Figure D-12. Modeled NMP Concentrations for Scenarios 3 and 6 Stripper Application in
Workshop using Parameter Values selected for Upper-end Non-User Exposure. . 116
Figure D-13. Modeled NMP Concentrations for Scenarios 7 and 8, Brush Application in
Bathroom using Parameter Values selected for Upper-end to Bounding User and
Non-User Exposures. ............................................................................................... 117
Figure F-1. Plot of mean response by dose (mg/m3) for fetal body weight with fitted curve for
Exponential model 2. ............................................................................................... 152
Exponential model 3. ............................................................................................... 153
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Authors / Contributors / Acknowledgements / Reviewers

This report was developed by the Office of Pollution Prevention and Toxics (OPPT), Office of
Chemical Safety and Pollution Prevention (OCSPP). The 2012 workplan risk assessments were
prepared based on existing data and any additional information received up to June 15, 2012.
EPA Assessment Team
Lead: Scott Prothero, OPPT/EETD
Team: Kent Anapolle, OPPT/EETD
Judith Brown, OPPT/EETD
Iris Camacho, OPPT/RAD
Mary Dominiak, OPPT/CCD
Ernest Falke, OPPT/RAD
Conrad Flessner, OPPT/EETD
Amuel Kennedy, OPPT/RAD
Andy Mamantov, OPPT/EETD
Justin Roberts, OPPT/EETD
Contributors
Chester E. Rodriguez, OPP/HED
Paul Schlosser, ORD/NCEA
Kan Shao, ORD/NCEA
Acknowledgements
Portions of this document were developed with support from:
Contractor name
Abt Associates
Eastern Research Group
Versar
SRC, Inc.
(contract number):
(EP-W-08-010)
(EP-W-10-014)
(EP-W-10-005)
(EP-W-09-027)
Production and Uses

Releases
Fate, Modeling, Monitoring
Technical Editing
Internal Peer Reviewers

H. Kay Austin, OPPT/EETD
Stan Barone Jr, OPPT/RAD
Todd Stedeford, OPPT/RAD
External Peer Review - A peer review panel is being arranged for this influential workplan
assessment product based upon need and following Agency peer review guidance. The format
will be a teleconference of an ad hoc panel meeting consisting of independent experts.
Page 8
Glossary of Terms and Abbreviations

C
2HMSI
5HNMP
ACH
ADC
ADR
AIC
AIHA
AUC
BAF
BCF
BMC
BMCL
BMCL 1SD
BMD
BMDS
BMR
BOD
BW
CASRN
CDC
cm
cm2
CO 2
DAF
DCM
DIY
DOC
dw
EC
EFH
EPA
EU
ft
ft2 or sq ft
FTIR
g
g/cm2
g/cm3
Degrees Celsius
2-Hydroxy-N-methylsuccinimide
5-Hydroxy-N-methyl-2-pyrrolidone
Air changes per hour
Average daily concentration
Acute dose rate
Akaikes Information Criterion
American Industrial Hygiene Association
Area under the curve
Bioaccumulation factor
Bioconcentration factor
Benchmark concentration
95 Percent lower confidence limit of the benchmark concentration
95 Percent lower confidence limit of one standard deviation of the benchmark
concentration
Benchmark dose
Benchmark Dose Software
Benchmark response
Biochemical oxygen demand
Body weight
Chemical Abstracts Service Registry Number
Center for Disease Control and Prevention
Centimeter(s)
Square centimeter(s)
Carbon dioxide
Dosimetry adjustment factor
Dichloromethane (or methylene chloride)
Do-it-yourself
Dissolved organic carbon
dry weight
European Commission
Exposures Factors Handbook
Environmental Protection Agency
European Union
Foot/feet
Square foot/feet
Fourier transform infrared
Gram(s)
Gram(s) per square meter
Gram(s) per cubic centimeter
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g/ft2
g/L
g/cm2-hour
g/minute
GD
H2S
HEC
HED
HHE
HPV
hr
IRIS
IURR
kg
L
Lb(s)
LC 50
LD 50
LOAEL
m2
m3
m/hour
m3/hr
MCCEM
mg
mg/cm2
mg/cm2-hour
mg/cm3
mg/g
mg/kg
mg/L
mg/m3
min
MITI
MMAD
mmHg
mmol
mmol/mol
MOE
mol
MRI
MSDS
MSI
NAICS
Gram(s) per square feet

Gram(s) per liter
Gram(s) per square meter per hour
Gram(s) per minute
Gestation day
Hydrogen sulfide
Human equivalent concentration
Human equivalent dose
Health hazard evaluation
High production volume
Hour(s)
Integrated Risk Information System
Inventory Update Reporting Rule
kilogram(s)
Liter(s)
Pound(s)
Lethal concentration 50 percent
Lethal dose 50 percent
Lowest-observed-adverse-effect level
Square meter(s)
Cubic meter(s)
Meter(s) per hour
Cubic meter(s) per hour
Multi-Chamber Concentration and Exposure Model
Milligram(s)
Milligram(s) per square centimeter
Milligram(s) per square centimeter per hour
Milligram(s) per cubic centimeter
Milligram(s) per gram
Milligram(s) per kilogram
Milligram(s) per liter
Milligram(s) per cubic meter
Minute(s)
Ministry of International Trade and Industry
Mass median aerodynamic diameter
millimeter of mercury
Millimole(s)
Millimole(s) per mole
Margin of exposure
Mole(s)
Midwest Research Institute
Material Safety Data Sheet
N-Methylsuccinimide
North American Industry Classification System
Page 10

NHANES
NIH
NIOSH
NMP
NOAEC
NOAEL
NOES
OCSPP
OECD
OPPT
OSHA
PBPK
PMN
POD
PPE
ppm
PVC
ROH
SCBA
SIC
SIDS
STEL
TRI
TSCA
TWA
UF
UF A
UF H
US
VOC
WEEL
WHO
National Health and Nutrition Examination Survey

National Institutes of Health
National Institute for Occupational Safety and Health
N-Methylpyrrolidone
No-observed-adverse-effect concentration
No-observed-adverse-effect level
National Occupational Exposure Survey
Office of Chemical Safety and Pollution Prevention
Organisation for Economic Cooperation and Development
Office of Pollution Prevention and Toxics
Occupational Safety and Health Administration
Physiologically based pharmacokinetic
Premanufacture Notification
Point of departure
Personal protection equipment
Parts per million
Polyvinyl chloride
Rest of the house
Self-contained breathing apparatus
Standard Industry Classification
Screening Information Data Set
Short-term exposure limit
Toxic Release Inventory
Toxic Substances Control Act
Time-weighted average
Uncertainty factor
Interspecies uncertainty factor
Intraspecies uncertainty factor
United States
Volatile organic compound
Workplace Environmental Exposure Level
World Health Organization
Page 11
Executive Summary
N-Methylpyrrolidone (NMP) was assessed as part of the United States (US) Environmental
Protection Agency (EPA) Existing Chemicals Management Program. EPA reviewed readily
available information on NMP including uses, physical and chemistry properties, fate, exposure
potential, and associated hazards to humans and the environment.
NMP was identified for assessment based on high concern for hazard due to its reproductive
toxicity, although the inclusion of more recent studies in this assessment indicates that NMP is
of low concern for this endpoint. This substance also ranked high for potential exposure
because it is widely used in consumer products, is present in drinking water and indoor
environments, and has high reported releases to the environment (US EPA, 2012c). NMP is
expected to have low persistence and low bioaccumulation potential in the environment.
NMP is produced or imported to the US in large quantities (i.e., over a range of 100 to 500
million pounds)/per year). It has a variety of uses including, petrochemical processing,
engineering plastics, coatings (i.e., resins, paints, finishes, inks, and enamels), paint stripping,
agricultural chemicals, electronic cleaning, and industrial/domestic cleaning. Though NMP is
reportedly used in a variety of consumer products, EPA found only a limited number of personal
care products (i.e., mascaras and nail polish) that were reported to contain NMP.
NMP is a colorless liquid that is a mildly volatile organic compound; therefore, inhalation
exposures may occur during its use. The Organization for Economic Cooperation and
Development (OECD) Screening Information Data Set (SIDS) program recently reviewed the
human health hazard profile for NMP. The OECD determined that dermal penetration through
human skin is very rapid and that prolonged exposures to neat (i.e., pure) NMP increased the
permeability of skin. For these reasons, both inhalation and dermal exposures to residential
and occupational use of NMP-containing paint stripping products were assessed by the Agency.
Paint stripping accounts for about nine percent of the total use of NMP. EPA assumed that
direct contact or close proximity to the use (i.e., for a consumer or commercial application with
substantial frequency or duration of exposure) would likely provide the highest exposures to
NMP paint strippers. Many of the other identified uses of NMP involve closed processes that
generally limit exposures and are of low concern.
EPA reviewed and summarized available published studies on aquatic toxicity to better
understand the potential ecological effects of NMP releases to the environment on aquatic
organisms including acute and chronic toxicity to invertebrates, fish, and plants, and toxicity to
birds. The ecological hazard of NMP is considered low, based on aquatic and terrestrial studies;
thus potential risks to ecological organisms based on releases of NMP from paint stripping
activities were not evaluated further in this assessment.
Occupational exposures were focused on workers employed by small commercial shops or
those that employ less than 10 workers. The remaining facilities (with >10 workers) were
Page 12

viewed by EPA as large-scale or unassigned operations and were not included in this
assessment. Large-scale manufacturing exposures are not addressed in this assessment
because EPA understands that such industrial operations are generally better controlled and
monitored than those exposures that may occur in the consumer/small-shop commercial
settings.
Occupational exposures by the dermal and inhalation routes of exposure were evaluated.
Chronic dermal exposure concentrations were estimated, whereas chronic inhalation exposure
concentrations were derived from published studies. Inhalation exposure data were only found
for paint stripping applications in the professional contracting and graffiti removal workplace
settings.
As a result of limited data on consumer exposures, EPA used modeling approaches to estimate
acute dermal and inhalation exposures to residential users of NMP-based paint stripping
products. Dermal exposures were estimated with the thin film modeling approach, and
variations in dermal dose were calculated for NMP paint strippers for brush- and spray-applied
formulations. Inhalation exposures to users and non-users (i.e., bystanders) were estimated
with the EPAs Multi-Chamber Concentration and Exposure Model (MCCEM). EPA evaluated
the sensitivity (i.e., by a sensitivity analysis) of the MCCEM input parameters (e.g., amount of
chemical applied, room air volume, rate of exchange between rooms, etc.).
Margins of exposure were calculated for occupational and consumer uses. Significant
uncertainties exist in EPAs dermal and chronic inhalation exposure estimates. For dermal
exposures, NMP is corrosive and the exposure scenarios assumed prolonged direct contact with
skin representing a worst case assumption, which may not represent real world conditions.
The available inhalation exposure data for workers and consumers are limited. This was
reflected in the wide range of MOEs, which spanned nearly four orders of magnitude. Thus, the
findings below should be viewed as uncertain. The following findings are limited to women of
child-bearing age, because the only observed toxicological endpoint is developmental toxicity.
Workers may have potential risks of concern from dermal exposure when no gloves are
worn.
Consumers may have potential risks of concern from dermal exposure assuming
appropriate gloves are not worn.
Consumers may have potential risks of concern from inhalation exposure (although of
lower concern than from dermal exposure) if exposed for more than 4 hours at lower
ventilation rates.
Page 13
Chapter 1: Background and Scope

INTRODUCTION
The chemical, N-methylpyrrolidone or 1-methyl-2-pyrrolidinone (NMP; Chemical Abstracts
Service Registry Number [CASRN] 872-50-4), was identified for assessment as part of the United
States (US) Environmental Protection Agencys (EPA)s Existing Chemicals Management
Program (http://www.epa.gov/oppt/existingchemicals/pubs/workplans.html).
NMP is a mildly volatile organic compound with moderate atmospheric photooxidation. It was
identified for further assessment by EPA initially based on concerns for reproductive toxicity;
however, more recent studies reviewed during EPAs initial scoping and evaluation indicate that
NMP is of low concern for this endpoint. This substance has high potential exposures because
it is widely used in consumer products, is present in drinking water and indoor environments,
and has high reported releases to the environment. NMP is expected to have low persistence
and low bioaccumulation potential in the environment.
NMP is currently on the candidate list of substances of very high concern for authorization in
the European Union (ECHA, 2011) and has been the subject of regulation by the EPA, including
listing on the Toxics Release Inventory (US EPA, 1994c). According to the 2010 TRI dataset, 370
facilities reported a total of 5.99 million pounds (lbs) of on- and off-site disposal and other
releases of NMP (US EPA, 2011b). The substance is not listed for an Occupational Safety and
Health Administration permissible exposure limit (PEL). NMP is currently approved for use by
EPA as a solvent and co-solvent pesticide inert in both food and non-food uses, and is exempt
from the requirement of a tolerance (40 CFR 180.920).
The human health hazard profile for the toxicity of NMP has been reviewed recently as part of
the Organization for Economic Cooperation and Development (OECD) Screening Information
Data Set (SIDS) program. The OECD showed that dermal penetration through human skin is
very rapid and that prolonged exposures to neat (i.e., pure) NMP increased the permeability of
the skin. NMP may cause skin swelling, blistering, and burns after prolonged direct contact
with skin (CPSC, 1995).
The ecological hazard of NMP is considered low, based on aquatic and terrestrial studies. This
substance has a low estimated bioaccumulation and bioconcentration such that the potential
bioconcentration in aquatic organisms has been determined to be low (OECD, 2007; US EPA,
2012a, 1999). Thus, the potential risks to ecological organisms based on releases of NMP from
paint stripping activities were not evaluated further in this assessment.
NMP is produced or imported into the US in large quantities (i.e., over a range of 100 to 500
million pounds (lbs)/yr). It has a variety of uses including petrochemical processing,
engineering plastics, coatings (resins, paints, finishes, inks, and enamels), paint stripping,
agricultural chemicals, electronic cleaning, and industrial/ domestic cleaning. EPA determined
Page 14

that NMP has a variety of household consumer uses, but is used in only a very few consumer
personal products (not regulated by TSCA) including mascaras and a nail polish remover (EWG,
2012). Though paint stripping accounts for only about nine percent of the total use of NMP,
EPA had specific concerns about this end-use, because paint stripping offers the greatest
potential for exposure. Many of the other identified uses of NMP involve closed processes that
generally limit exposures and are of low concern.
In the following section, the focus and scope of EPAs risk assessment of NMP is described.
SCOPE OF THE ASSESSMENT

This assessment focused on the use of NMP in paint strippers. EPA assumed that direct contact
or close proximity to the use (i.e., for a consumer or commercial application with substantial
frequency or duration of exposure) would likely provide the highest exposures to NMP-based
paint strippers. In either consumer or occupational settings, there may be dermal and/or
inhalation exposures during the use of these products. There also may be oral ingestion of
these products, but EPA determined this exposure route was less likely and of less concern,
thus it was not evaluated further. In addition to product users, there also may be non-users or
bystanders who may not come in direct contact with the product, but may be exposed
indirectly via inhalation while in a nearby area during product application.
NMP is a colorless liquid that is a mildly volatile organic compound; therefore, inhalation
exposures may occur during its use. The Organization for Economic Cooperation and
Development (OECD) Screening Information Data Set (SIDS) program recently reviewed the
human health hazard profile for NMP. The OECD determined that dermal penetration through
human skin is very rapid and that prolonged exposures to neat (i.e., pure) NMP increased the
permeability of skin. For these reasons, both dermal and inhalation exposures to residential
and occupational use of NMP-containing paint stripping products were assessed by the Agency.
While paint stripping accounts for only about nine percent of the total use of NMP, EPA
assumed that direct contact or close proximity to the use (i.e., for a consumer or commercial
application with substantial frequency or duration of exposure) would likely provide the highest
exposures to NMP paint strippers. Many of the other identified uses of NMP involve closed
processes that generally limit exposures and are of low concern.
EPA understands that exposures that result from large-scale industrial operations are generally
monitored and well controlled. Exposures in small commercial or consumer settings may not
adhere to the same types of controls. Thus, large-scale manufacturing occupational exposure
scenarios were not addressed in this assessment. Rather, EPA focused this assessment on
exposures to workers employed by small commercial shops. For the purpose of this
assessment, EPA considered a small shop as one that employs less than 10 workers (i.e., the
remaining facilities were considered large facilities and were not considered in this
assessment). Other uses beyond paint stripping were not evaluated in this assessment.
Page 15

EPA reviewed and summarized available published studies on aquatic toxicity to better
understand the potential ecological effects of NMP releases to the environment on aquatic
organisms including acute and chronic toxicity to invertebrates, fish, and plants, and toxicity to
birds (Appendix A). The ecological hazard of NMP is considered low, based on aquatic and
terrestrial studies (OECD, 2007; US EPA, 2012a, 1999); thus, potential risks to ecological
organisms based on releases of NMP from paint stripping activities were not evaluated further
n this assessment.
Page 16
Chapter 2: Sources and Environmental Fate

INTRODUCTION
To assess the human health risk concerns of N-methylpyrrolidone or 1-methyl-2-pyrrolidinone
(NMP), a firm understanding of the physical and chemical properties, sources related to
production and uses, and fate in the environment is important. These topics are introduced in
Chapter 2 and discussed in relation to the risk characterization in Chapter 3.
2.1. CHEMICAL AND PHYSICAL PROPERTIES
The chemical structure for NMP is shown in Figure 2-1.
Figure 2-1. Chemical Structure of NMP.
NMP is a colorless to slightly yellow liquid with a slight amine odor that is typically used as a
solvent. A summary of the most relevant physical and chemical properties of NMP are
provided in Table 2-1. NMP is in a class of dipolar aprotic solvents that are miscible in water
(water solubility = 1,000 g/L at 25 C; log K ow = -0.727 at 25 C); aprotic solvents do not contain
acidic hydrogen. NMP exhibits mild volatility (i.e., vapor pressure = 0.190 Torr at 25 C), high
boiling point (202 C), low flammability, no explosivity, and relatively low toxicity. However,
variations in humidity can cause a range of saturation concentrations. Also, NMP is not readily
oxidizable (Lide, 2001; EC, 2000; O'Neil et al., 2001).
Table 2-1. Physical-Chemical Properties of NMP.
Molecular formula
C 5 H 9 ON
Molecular weight
99.13
Physical form
Colorless to slightly yellow liquid; slight amine odor
Melting point
-24.4 C
Boiling point
202 C
Vapor pressure
0.190 mmHg at 25 C
Log K ow
-0.727 at 25 C
Water solubility
1,000 g/L at 25 C
Flash point
95 C (open cup); 91 C (closed cup)
Source: EC (2000).
Page 17
2.2. PRODUCTION VOLUME AND USES

NMPs chemical name, CASRN, and 2006 TSCA Inventory Update Reporting Rule (IURR)
production volume are provided in Table 2-2. The 2006 public IURR indicates that 100 million
to 500 million lbs of NMP were produced or imported into the US that year, making NMP a high
production volume (HPV) chemical (US EPA, 2010a). BASF Corporation, International Specialty
Products, Inc., and Lyondell Chemical Company currently manufacture NMP in the US.
Table 2-2. NMP Production Volume Information.
CASRN
872-50-4
CA Index Name
1-Methyl-2-pyrrolidinone
Acronym
NMP
IURR Production Volume

100-500 million lbs
Source: US EPA (2010a).
NMP is an effective solvent used in a variety of industrial, commercial, and consumer use
applications, including: as listed below (Harreus et al., 2011):
Petrochemical processing, acetylene recovery from cracked gas, extraction of

aromatics and butadiene, gas purification (removal of carbon dioxide [CO 2 ] and
hydrogen sulfide [H 2 S]), lube oil extraction
Engineering plastics: reaction medium for the production of high-temperature

polymers such as polyethersulfones, polyamideimides, and polyaramids
Coatings: solvent for acrylic and epoxy resins, polyurethane paints, waterborne
paints or finishes, printing inks, synthesis/diluent of wire enamels, coalescing agent
Agricultural chemicals: solvent and/or cosolvent for liquid formulations
Electronics: cleaning agent for silicon wafers, photoresist stripper, auxiliary in

printed circuit board technology
Industrial and domestic cleaning: component in paint strippers and degreasers (e.g.,
removal of oil, fat, and soot from metal surfaces, and carbon deposits and other
tarry polymeric residues in combustion engines)
Other use applications also have been reported inducting: microelectronics industry plastic
solvent; extraction of acetylene and butadiene; metal finishing; printed circuit board
manufacturing; dehydration of natural gas; spinning agent for polyvinyl chloride (PVC); lube oil
processing; petrochemical processing; pigment dispersant; and adjuvant for slimicides in foodcontact paper (Ash and Ash, 2009).
Though paint stripping accounts for only about nine percent of the total use of NMP, EPA is
specifically concerned about this use, because the potential for exposure is high; many of the
other uses of NMP involve closed processes (TURI, 1996). While the cited paint stripping use
percentage is from reports dated in the 1980s and 1990s, proprietary information (i.e., known
but not cited here) as recent as 2011 confirmed that paint stripping is still a low percentage use
for NMP in terms of market consumption.
Page 18

2.2.1. Consumer Uses
The 2006 IURR data indicate that NMP is used in the following commercial and consumer use
categories: electrical and electronic products and paints and coatings (US EPA, 2010a). The
National Institutes of Health (NIH) Household Products Database currently lists 47 products
containing NMP, in concentrations ranging from one to 100 percent. The product forms include
liquid, aerosol, kit, paste, and pump spray (NIH, 2012). Furthermore, according to the
Environmental Working Groups Skin Deep Cosmetics Database, six cosmetic products contain
NMP: five mascara products and one nail polish remover (EWG, 2012).
Table 2-3 presents the major consumer uses of NMP, which represent <30 percent of the total
domestic NMP market.
Table 2-3. Consumer Uses of NMP.
Consumer Uses
Auto products
Leather cleaner/conditionera
Rubbing compounda
Paint protectanta
Cleaner for fuel injection/carburetora
Arts and crafts products
Stripper/paint removera
Home maintenance products
Adhesive removera
Paint, varnish, wood stain, etc.a
Wood sealanta
Paint strippera
Graffiti removera
Brush cleanera
Floor finisha
Floor cleanera
Pesticides
Fungicidea
Herbicidea
Insecticidea
Cosmetics
Polish removerb
Mascarab
NIH (2012).
EWG (2012).
2.2.2. Paint Stripping Applications

Some states have done extensive research about the paint stripping market which is of interest
to the EPAs assessment of NMP. In the State of California, there are approximately 80 facilities
that have stripping equipment and use relatively large quantities of stripper that they typically
purchase in quantities ranging in size from five- to 55-gallon drums. Other companies provide
on-site services to consumers for stripping kitchen or office cabinets for which they purchase
product from paint supply or hardware stores. There are approximately 500 additional facilities
Page 19

in the state that do some stripping as part of their business, which would include small shop
facilities like antique shops; these facilities purchase small quantities of stripper from hardware
or paint supply stores. Residential/consumers also purchase stripper from paint supply and
hardware stores (Cal EPA, 2006).
2.3. CONCLUSIONS ON PRODUCTION VOLUME AND USES

NMP is a high production volume chemical (US EPA, 2010a). Though paint stripping accounts
for only about nine percent of the total use of NMP, EPA is specifically concerned about this
use, because the potential for exposure is high; many of the other uses of NMP involve closed
processes which typically have little exposure and are of less concern. NMP is used as an
alternative for DCM in paint stripping applications and both paint strippers were identified for
assessment as part of the EPAs Existing Chemicals Management Program
(http://www.epa.gov/oppt/existingchemicals/pubs/workplans.html).
2.4. ENVIRONMENTAL FATE

The environmental fate of a compound is important to understanding its potential impact on
specific environmental media (e.g., water, sediment, soil, and plants) and exposures to target
organisms of concern. Due to its mild volatility, it is possible for NMP to enter the atmosphere
where moderate photooxidation may occur by reaction with photochemically produced
hydroxyl radicals. Releases of NMP to soil may volatilize from soil surfaces or migrate through
soil and contaminate groundwater. NMP has been shown to biodegrade readily. This section
summarizes current knowledge of the transport, persistence, bioaccumulation, and
bioconcentration of NMP in the environment including biological and abiotic reactions and
environmental distribution.
2.4.1. Fate in Air
If released to the atmosphere, NMP is expected to exist solely in the vapor-phase based on its
vapor pressure. Vapor-phase NMP is degraded in air by reaction with photochemically
produced hydroxyl radicals. The half-life of this reaction is approximately 5.8 hours, assuming a
hydroxyl radical concentration of 1.5 106 hydroxyl radicals/cm3 air over a 12-hour day.
2.4.2. Fate in Water
When released to water, NMP is not expected to adsorb to suspended solids or sediment in the
water column based upon its K oc value. The rate of volatilization from water is expected to be
low based on a Henrys Law constant of 3.2 10-9 atm-m3/mole. Biodegradation is expected to
occur rapidly in aerobic waters. NMP, present at 100 mg/L, achieved 73 percent of its
theoretical biochemical oxygen demand (BOD) in four weeks using an activated sludge
inoculum and the Japanese Ministry of International Trade and Industry (MITI) test (OECD
301C). It was not readily biodegradable in a standard closed bottle (OECD 301C) test; however,
Page 20

it achieved 88 percent of its theoretical BOD using a modified procedure in which the mineral
nutrient solution was fortified with the essential vitamin and trace metal solutions and a preacclimation procedure was applied to the inoculum. NMP was degraded 91 percent as
measured by CO 2 evolution and 91 percent as measured by dissolved organic carbon (DOC)
removal using the AFNOR (OECD 301A) test. NMP passed an inherent biodegradation test,
degrading 98 percent after four days using the Zahn-Wellens (OECD 302B) method. These data
suggest that NMP will not be persistent in aerobic surface waters. NMP is not expected to
hydrolyze in water since it does not contain functional groups that are typically susceptible to
hydrolysis under environmental conditions.
2.4.3. Fate in Soil and Sediment
Based on its low soil organic carbon partitioning coefficient (log K oc = 0.9), NMP is likely to
possess high mobility in soils and may leach from soils into groundwater. Volatilization is
expected to be low given the Henrys Law constant of this compound. It is not expected to be
persistent in the environment. It was shown to be both readily biodegradable and inherently
biodegradable in several OECD screening tests. NMP was incubated for up to three months in
soils at an initial concentration of 1.7 mg/kg dw. The half-lives were 4, 8.7, and 11.5 days in
clay, loam, and sandy soil, respectively. After 21 days, the extractable level of NMP had
dropped below 0.1 mg/kg dw for all soils tested.
2.4.4. Bioconcentration and Persistence
Bioconcentration and persistence are qualitatively characterized according to the criteria set
forth in the Premanufacture Notification (PMN) program (US EPA, 1999). Measured
bioconcentration studies for NMP were not located; however, the estimated bioaccumulation
factor (BAF) and bioconcentration factor (BCF) of 0.9 and 3.16, respectively, suggest that
bioaccumulation and bioconcentration in aquatic organisms is low. Biodegradation studies
have consistently shown this substance to be readily biodegradable. Based upon the
experimental evidence and environmental fate data available, NMP is expected to have low
bioaccumulation potential and low persistence.
Table 2-4 provides a summary of the environmental fate information for NMP1.
Page 21
Table 2-4. Environmental Fate Characteristics of NMPa.

Property
Value
CASRN
872-50-4
Photodegradation half-life
5.8 hours (estimated)
Hydrolysis half-life
Stable
Biodegradation
Half-life of 4 days in a clay soil

Half-life of 8.7 days in a loam soil
Half-life of 11.5 days in a sandy soil
73% after 28 days (readily biodegradable, OECD 301C)
91-97% after 28 days (readily biodegradable, OECD 301A)
88% after 30 days (readily biodegradable, OECD 301D)
98% after 4 days (inherently, biodegradable, OECD 302B)
99% after 8 days (inherently biodegradable, OECD 303A)
Bioconcentration
BAF = 0.9 (estimated)b

BCF = 3.16
Log K oc
0.9 (estimated)b
Fugacity
(Level III Model)b
Air (%)
Water (%)
Soil (%)
Sediment (%)
0.1
32.5
67.3
0.1
Persistencec
low
Bioaccumulationc
low
OECD (2008).
US EPA (2012a).
c
US EPA (1999).
b
2.5. CONCLUSIONS OF ENVIRONMENTAL FATE

NMP is expected to possess high mobility in soil. Numerous studies indicate that NMP is both
readily and inherently biodegradable, and is not expected to be persistent in the environment.
The rate of hydrolysis is negligible. Volatilization is considered low given its Henrys Law
constant of 3.2 10-9 atm-m3/mole. The rate of atmospheric photooxidation is moderate. No
measured bioconcentration data were located; however, the low estimated bioaccumulation
and bioconcentration factors, 0.9 and 3.16, respectively, suggest that bioconcentration in
aquatic organisms is low (OECD, 2007; US EPA, 2012a, 1999).
Page 22
Chapter 3: Human Health Risk Assessment

INTRODUCTION
EPA reviewed readily available information on the chemistry, uses, sources, fate, exposure, and
hazard of NMP to humans and the environment. The review of this information helped focus
the scope of this risk assessment. Biomonitoring data were reviewed, but were not used for
the risk analyses. A summary of these data is provided in Appendix E. This chapter has five
major sections: (1) Exposure Assessment; (2) Hazard Summary and Dose Response
Information; (3) Risk Characterization; (4) Discussion of Uncertainties and Data Gaps; and (5)
Conclusions.
3.1. HUMAN EXPOSURE ASSESSMENT

This assessment focused on the use of NMP in paint strippers. EPA assumed that direct contact
or close proximity to the use (i.e., for a consumer or commercial application with substantial
frequency or duration of exposure) would likely provide the highest exposures to NMP-based
paint strippers. In either consumer or occupational settings, there may be dermal and/or
inhalation exposures during the use of these products. There may also be oral ingestion of
these products, but EPA determined this exposure route was less likely and of less concern,
thus it was not assessed. In addition to product users, there also may be non-users or
bystanders who may not come in direct contact with the product, but may be exposed
indirectly while in a nearby area during product application.
EPA focused the exposure assessment on the dermal route. NMP has a low vapor pressure (i.e.,
0.190 mmHg at 25 C) and mild volatility, so that inhalation exposures are of less concern.
Taking this approach is consistent with the recent OECD determination that dermal penetration
through human skin is very rapid and prolonged exposures to neat (i.e., pure) NMP increases
the permeability of the skin. To quantify potential risks of concern, EPA focused on assessing
acute dermal exposures to residential users and acute inhalation exposures to residential
users/non-users. Dermal exposures likely would be negligible for residential non-users located
at a distance from the product use area; therefore, this route of exposure was not assessed for
residential non-users. For workers, chronic dermal and inhalation exposures were assessed.
The exposure assessment has two main sections covering non-occupational/residential and
occupational exposures.
3.1.1. Occupational Exposures
This section addresses dermal and inhalation exposures in workplace settings. According to the
1983 National Occupational Exposure Survey (NOES), over 25,000 US employees were exposed
to NMP at 2,450 facilities. Thirteen percent of these exposures occurred during manufacture,
Page 23

whereas 87 percent of the exposures occurred from NMP-based product use (US EPA, 1990).
To estimate occupational dermal and inhalation exposures to NMP during paint stripping
activities in workplace settings, EPA conducted a literature search to identify published
exposure studies and existing data on exposure concentrations and activity patterns (i.e.,
duration of exposure, etc.). No studies for dermal occupational exposures were found, and
only a limited number of inhalation exposure studies were identified.
Chronic occupational dermal exposures were estimated by modeling dermal exposures to NMP
in liquid products. To estimate chronic inhalation exposures to workers using NMP paint
stripping products, EPA used existing exposure data from a limited number of observational
studies. Appendix C contains a summary of relevant data and a description of the modeling
information and approach.
3.1.2. Background and Context of Paint-Stripping Industry
Background. To better understand the potential extent and impact of occupational exposures
to NMP, this section presents information on industry sectors that employ potentially exposed
worker populations and exposure levels to workers using NMP-based paint stripping products.
Also included is a summary of non-regulatory exposure limits that can affect exposures.
Occupational Exposure Limits. The Occupational Safety and Health Administration (OSHA) has
not established regulatory exposure limits for NMP. The only recommended exposure limit
identified for NMP is a non-regulatory limit established by the American Industrial Hygiene
Association (AIHA) workplace environmental exposure level (WEEL) of 10 ppm for an eight-hr
Time Weighted Average (TWA), with the addition of a cautionary note addressing concerns for
skin contact (AIHA, 2011). EPA believes that some workplaces may consider this WEEL when
instituting respiratory protections.
Industries that Employ Paint Stripping Activities. A number of industries include paint
stripping among their business activities. EPA used the 2007 North American Industry
Classification System (NAICS) codes to identify industries likely to include paint stripping
activities. Table 3-1 provides the NAICS codes for industries with paint stripping activities.
Appendix C provides additional information on: the approach for identifying industries likely to
use NMP-based paint strippers, paint stripping processes and associated worker activities,
facility and worker population data, and respiratory and dermal protection.
Table 3-1. 2007 NAICS Codes Identified that Include Paint Stripping Activities.
2007 NAICS
2007 NAICS Title
Rationale for Inclusion of NAICS with Paint Stripping

Activities
238320
Painting and wall covering

contractors
US Census reports an index entry of Paint and wallpaper

stripping (US Census, 2007b).
238330
Flooring contractors
US Census reports index entries of Floor laying, scraping,

finishing, and refinishing and Resurfacing hardwood
flooring(US Census, 2007b). The National Institute for
Page 24

Occupational Safety and Health (NIOSH) cites the paint
stripping of flooring by a wood flooring and restoration
company (NIOSH, 1993).
811121
Automotive body, paint, and

interior repair and maintenance
NAICS code 811121 is identified for automobile

refinishing per the OECD Coating Application via SprayPainting in the Automotive Refinishing Industry ESD
(OECD, 2010).
811420
Reupholstery and furniture repair US Census reports index entries of Furniture refinishing
shops and Restoration and repair of antique furniture
(US Census, 2007b).
711510
Independent artists, writers, and

performers
US Census reports index entries of Painting restorers,

independent and Conservators (i.e., art, artifact
restorers), independent (US Census, 2007b). Research
has shown art conservation to use paint strippers based
on DCM or, preferably, NMP (Wollbrinck, 1993).
712110
Museums
Research has shown art conservation to use paint

strippers based on DCM or, preferably, NMP (Wollbrinck,
1993).
336411
Aircraft manufacturing
US Census reports an index entry of Aircraft rebuilding

(i.e., restoration to original design specifications) (US
Census, 2007b). Paint removal during the restoration
process may use DCM- or NMP-based paint strippers.
336611
Ship building and repairing
US Census 2007 NAICS definition includes shipyards

involved in the construction of ships as well as their
repair and conversion and alteration (US Census, 2007b).
Any paint removal activities during repair, conversion,
and alteration may use DCM- or NMP-based paint
strippers.
Size of Paint Stripping Facilities. Because EPA expects that small commercial shops may not
strictly adhere to monitoring and control measures to limit worker exposures to NMP in paint
stripping applications, EPA focused this assessment on exposures to workers employed by
small commercial shops (i.e., less than 10 workers). EPA identified published information to
characterize these industries for potential occupational exposures; however, the data and
background information were not sufficient to estimate the total number of employees per
facility in each of the potentially exposed populations. The Agency made some generalizations
about the relative sizes of small commercial facilities or shops that employ paint-stripping
workers. Using the facility and population data from Appendix D, the industries included in this
assessment were categorized using an average number of employees per facility into the size
classifications as follows:
Small shops could generally be expected to include facilities with <10 workers (e.g.,
professional contractors, automotive refinishers, furniture refinishers, and
independent art restorers, etc.):
Page 25
Larger facilities could generally be expected to include facilities with >10 workers
(e.g., aircraft and ship paint stripping, etc.);
The exposures labeled Graffiti Removers or Unspecified Workplace Setting cannot
be classified into either small shop or larger facilities.
These simple size distinctions may not be entirely applicable to the exposure data in the
industry categories identified.
3.1.3. Occupational Dermal Exposure Assessment
Background. Because EPA found no published data to assess dermal exposures to small
commercial shop workers, dermal exposures were estimated using a standard generic thin film
modeling approach (i.e., the EPAs 2-Hand Dermal Contact with Liquid Model). EPA assumed
that small commercial shop workers did not wear protective gloves while working with NMPbased paint stripping products. This approach uses a more conservative or worst case
assumption that confers a more protective approach to assessing the potential risks of concern.
EPA did not assess exposures to workers wearing gloves.
Model Assumptions. EPA utilizes a series of standard models to quantitatively estimate dermal
exposures to liquid and solid chemicals in workplace settings. To estimate occupational dermal
exposure, all of the models assume the following default values: a specific skin surface area
contacted by a material containing the chemical of interest; a specific surface density of the
material on the skin (i.e., quantity of the liquid or solid material containing the chemical that
remains on the skin after contact); and no use of personal protective equipment (e.g., gloves)
to reduce the exposure. These assumptions and default parameters were defined based on the
nature of the exposure (e.g., one hand or two hand, immersion in material, and contact with
surfaces, etc.). Details on EPAs dermal exposure model are outlined in Appendix D.
Table 3-2 shows EPAs assumptions for the modeling parameters (e.g., number events per day,
skin area exposed, and body weight, etc.) used to estimate dermal exposures to workers using
NMP paint strippers. In addition to these assumptions, EPA also assumed 100 weight percent
NMP and maximal absorption through the skin (i.e., 100 percent; (SCCS, 2011)).
Table 3-2. Summary of Worker Dermal Model Parameters and Resultsa.
Result Description
Weight
Fraction
F chem
Surface
Density of
Film
Skin
Surface
Area
Q remain_skin AREA surface

2
Frequency of
Events
Body
Weight
Normalized
Dermal
Exposure
N event
BW worker
EXP dermal_bw
(Unitless)
(mg/cm )
(cm )
(Events/day)
(kg)
(mg/kg-day)
Low end of range
100
0.7
840
80
7.4
High end of range
100
2.1
840
80
22
Appendix C contains the model equations and explanation.
Page 26

Model Results for Occupational Dermal Exposures. The following results were estimated using
the model equations:
Dermal exposure to liquid (EXP dermal ) of 590 to 1,800 mg NMP/day; and,
Dermal exposure normalized by body weight (EXP dermal_bw ) of 7.4 to 22 mg NMP/kgday as potential dose rates.
Absorbed dose rates may be assumed to be equal to potential dose rates.

Limitations of the Occupational Dermal Exposure Analysis. There were no published data
available to develop statistical distributions of exposure for worker populations, so a modeling
approach was used to estimate occupational dermal exposures. There are limitations to the
analysis that include: 1) the resulting dermal potential dose rates show a wide range of
variability; 2) most of the model input parameters were default values which may not reflect
the conditions in workplace settings; and, 3) the representativeness of the model results to the
broader worker populations that are exposed to NMP during its use in various paint stripping
products and applications cannot be determined.
3.1.4. Occupational Inhalation Exposure Assessment
This section provides estimates of inhalation exposure for occupational use of paint-stripper
products containing NMP for users and non-user/bystanders. To estimate inhalation exposures,
EPA conducted a literature search for industries using NMP products. EPA used existing
exposure data from a limited number of observational studies to establish a reasonable range
of exposure concentrations.
Occupational Inhalation Exposure. Table 3-3 summarizes the available published data that EPA
located for ranges of NMP inhalation exposures for two exposed populations (i.e., Professional
Contractors and Graffiti Removal). However, information for other industries utilizing NMP
paint stripping applications was identified, but there was insufficient data to include them in
the assessment (i.e., see Appendix C for more information on these industries). EPA used
available data on ranges of inhalation exposures to workers and Average Daily Concentration
(ADC) values were calculated from available eight-hr TWA exposures (i.e., using Equation 3-1).
ADC Calculations. ADCs is calculated from Equation 3-1 (US EPA, 2009). It is equivalent to EC in
the equation below, with the substitution of the appropriate averaging time (AT) value.
(Eq. 3-1)
where:
EC
=
C
=
ED
=
EF
=
WY
=
AT
=
exposure concentration (mg/m3);

contaminant concentration in air (mg/m3);
exposure duration (hours/day; default: 8);
exposure frequency (days/yr; default: 250);
working years per lifetime (yrs; ADC : 40 yrs); and
averaging time (lifetime in yrs 365 days/yr 24 hours/day; ADC: 40 yrs).
Page 27

Table 3-3. Summary of Ranges of NMP Inhalation Exposures and Calculated ADCs for Workers.
Industry
Range of TaskRange of 8-hr TWA

Number of Time Range Based, Short-Term,
Exposures
ADC (mg/m3)c
Studies
of Studies or Peak Exposures
3 b
(mg/m )
(mg/m3)a
Professional
contractors
19931994
13-39
(3.3-10 ppm)
Graffiti removal
1993-2004
0.01-30
(0.002-7.4 ppm)
2000
0.03-4.5
(0.007-1.1 ppm)
0.007-1.0
These exposures include task-based exposures averaged over a time period of <8 hrs, short-term (i.e., short-term
3
exposure limit [STEL]) exposures, and peak exposures. Exposures are provided in units of mg/m , except values in
parentheses are in units of ppm (by volume).
b
These exposures include 8-hr TWA exposures that were either directly measured or calculated from shorter time
frame exposures by the study authors.
c
ADCs are only calculated from 8-hr TWA exposures.
3
Note: Airborne concentration conversion factor for NMP is 4.06 mg/m per ppm (see Appendix C).
Limitations of the Occupational Inhalation Exposure Analysis. Limitations were identified with
the observational studies that EPA used to estimate worker exposures to NMP paint strippers.
These limitations included the following: 1) there were few studies available that provided
enough useful data or background information to develop statistical distributions of exposure
for the populations; 2) the available exposure concentration data were extremely variable; and
3) the representativeness of the available data to the broader worker populations exposed to
NMP during its use in various paint stripping applications cannot be determined. The variability
in the derived exposure concentrations (Table 3-3) was significant and precluded EPA from
deriving relevant margins of exposure (MOEs) for occupational inhalation exposures.
3.1.5. Residential Exposure Assessment
This section provides estimates of dermal and inhalation exposures for residential/consumer use
of paint-stripper products containing NMP. These exposures were assessed using a modelingbased approach; acute dermal exposures were calculated for product users only, while acute
inhalation exposures were calculated for both users and non-users. A thin-film modeling
approach, similar to that used for the occupational dermal exposure assessment, was used to
predict consumer dermal exposures. EPAs Multi-Chamber Concentration and Exposure Model
(MCCEM) was utilized to predict concentrations in air to estimate consumer inhalation
exposures to an NMP- based paint stripper in various hypothetical consumer-use scenarios.
3.1.6. Residential Dermal Exposure Assessment
To better understand potential risks of concern to consumers from the use of NMP-containing
paint stripping products, EPA conducted a dermal exposure assessment. Estimates were made
Page 28

of central-tendency (i.e., near average or median) exposures and upper-end (i.e., plausible
exposures from the upper half of expected exposure amounts); these exposure estimates are
generally required for risk assessments.
Dermal Exposure Assessment Methodology. Dermal exposures for consumer use of NMP paint
strippers were calculated using a similar approach to that for occupational dermal exposures,
the thin-film modeling approach described in US EPA (1996) and US EPA (2007). However,
unlike with the occupational assessment, default values were not used for all of the input
parameters. The following values were derived : 1) the weight fraction values for consumer
products are well enough understood to derive central tendency (median) and high end (90th
percentile) values for both the brush-on and spray-on products (Cf. the occupational model
assumed a value of 1, i.e., 100 percent NMP); 2) the film thickness value in the consumer
modeling was based on a professional judgment estimate based on information from a chemist
employed by a paint stripper manufacturer (Cf. the occupational model used surrogate values
based on measured film thickness from several non-paint-stripper surrogate liquids); 3) the
surface area for the exposed skin in the consumer modeling assumed that half of each average
adult hand would be exposed (Cf. the occupational model assumed a 70 percent greater
surface area); and, 4) because there were limited data available for the dermal model input
parameters, central and high-end scenarios for each application type (i.e., brush or spray) were
constructed by varying the weight fraction of the applied product. More discussion of these
values can be found in the Discussion of Key Sources of Uncertainty and Data Limitations of this
chapter, and the dermal exposure modeling sections for occupational exposures in Appendix C.
The model equation, expressed in the form of the acute dose rate (ADR), is provided below in
Equation 3-2.
ADR dermal =
(Eq. 3-2)
Where:
ADR dermal (mg/kg-day) = acute dose rate
WF (unitless) = weight fraction (used in place of concentration)
PD (mg/cm3) = product density
FT (cm) = film thickness
SA (cm2) = surface area
ED (days) = exposure duration
FQ (events/day) = frequency of use
BW (kg) = body weight
AT (days) = averaging time
Dermal Exposure Scenarios. Four different dermal exposure scenarios were evaluated as
shown in Table 3-4 (i.e., see Dermal Assessment Inputs in Appendix D for more detail). Dermal
exposures were calculated for the adult user not wearing protective gloves. EPA assumed that
dermal exposure to other residential occupants, i.e., non-users, was unlikely and therefore was
Page 29

not assessed. Dermal exposure scenarios were completed for both brush-on and spray-on
paint stripping applications.
Table 3-4. Estimated Consumer Dermal Exposure Results.
Case Scenario
ID Description
Weight
Fraction
WF
Product
Film
Surface Exposure Frequency Body Averaging
of Use Weight
Density Thickness Area Duration
Time
PD
3
(Unitless) (mg/cm )
FT
SA
(cm)
Acute
Dermal
Exposure
ED
FQ
BW
AT
ADR dermal
(cm )
(Days)
(Events/
day)
(kg)
(Days)
(mg/kgday)
Brush-on,
central
0.25
1,100
0.03
490
80
50
Brush-on,
high-end
0.50
1,100
0.03
490
80
100
Spray-on,
central
0.44
1,100
0.03
490
80
89
Spray-on,
high-end
0.53
1,100
0.03
490
80
110
Dermal Exposure Modeling Results. Results from the dermal exposure calculations are
described in Table 3-4. Estimates of acute dermal exposures for consumer users of NMP paint
stripping products ranged from 50 to 100 mg/kg-day for the brush-on scenarios and from 89 to
110 mg/kg-day for the spray-on scenarios.
Limitations of Dermal Assessment. The exposure estimates for consumer NMP paint stripping
product users are considered hypothetical as a result of uncertainties with the model input
parameters, especially with the assumptions for film thickness and surface area of skin that
would be exposed to the paint stripping product. One important uncertainty in the dermal
model is with the assumption that with each exposure event, only one thin film contacts the
skin. This uncertainty was addressed in US EPA (1996) which stated that the number of times
that a person contacts the paint remover product per exposure event is unknown.
In the consumer dermal exposure scenarios, all parameters have equal sensitivity; thus, a
change in a parameter value will provide direct proportional changes in the acute dermal
exposures.
3.1.7. Residential Inhalation Exposure Assessment
Background. In the absence of representative air monitoring data, MCCEM was used to
estimate consumer inhalation exposure concentrations. The parameters needed to support the
modeling effort, i.e., model input values and the rationale for their use in different exposure
scenarios, are described in this section.
Page 30

Model Input Parameters and Rationale. MCCEM requires inputs of several chemical-specific
parameters including values for: current product characteristics, use patterns, exposure factors,
and air concentrations to develop appropriate exposure scenarios. The majority of the source
documents EPA used for these input values were over a decade old. All sources were
compared to EPA quality criteria (i.e., currency, scope, accuracy/reliability, transparency, clarity,
and completeness of the information provided).
EPA used published values for NMP-containing products currently available for consumer
purchase to determine reasonable percentages of NMP in products and product densities
(Brown, 2012). Other resources that provided information on product characteristics included:
(1) the NIHs Household Products Database; (2) Material Safety Data Sheets; and (3) Product
Labels and Technical Data Sheets (i.e., TDS). The information collected from available product
labels or TDSs included approximately half of the products listed in Brown (2012).
In the absence of actual air monitoring data for consumer use of an NMP paint stripper, EPA
reviewed several air monitoring studies for consumer paint strippers that used DCM-containing
products, including US EPA (1994b), EC (2004), a Consumer Product Safety Commission study
(as cited in US EPA, 1996; and Riley et al., 2000), and a study conducted in the Netherlands by
van Veen et al. (2002). EPA determined, however, that data from these studies could not be
used for this assessment because of differences in the chemical properties between NMP and
DCM. Most importantly, NMP has a much lower volatility and emission rate than DCM.
Additionally, these studies generally did not reflect current use patterns in the US, did not
provide sufficient raw data to support necessary calculations, and/or were conducted using test
chambers that did not provide air concentrations for areas other than the application room.
To estimate air concentrations for consumer inhalation exposures, EPA identified published air
monitoring data from one occupational study. This experimental study was conducted for EPA
(US EPA, 1994b). Despite its age, the study and the data were considered accurate,
transparent, and complete. In that study, chamber experiments were conducted for five paint
stripping products including one product containing 65 to 70 percent NMP (i.e., fairly high
concentration). However, the experimental data could not be used directly to model
residential inhalation exposures because the values for the required exposure factors (e.g.,
room/house volume, airflow rates, and surface area of object) were not entirely representative
of the range of residential values. Additionally, the experiments (US EPA, 1994b) were
conducted in a one-room chamber which did not provide concentrations for areas of the house
other than the treatment room. An advantage of this study was that it used a US product and
provided sufficient descriptions of the study design and results. The study was useful in
determining product application rates (i.e., in g/ft2 and g/minute) and in estimating the fraction
of applied chemical mass released to indoor air (i.e., details described in Appendix D).
Information on exposure-factors was identified from a variety of sources, including the EPAs
Exposure Factors Handbook (EFH) (US EPA, 2011c). The EFH provides information on generic
exposure factors such as body weights, body part surface areas, house volumes, and house
Page 31

ventilation rates. Information on specific uses of paint strippers (i.e., use amounts, frequencies,
and durations) was obtained from WESTAT (1987) and Abt (1992).
EPA utilized some additional information on use patterns of paint strippers as reported by Riley
et al. (2001). This study had some limitations, including: a single-site survey was used in the
study; it was not specific to NMP paint strippers; it was based on a small sample size (n = 20);
and it was based on respondent recall of product-use behavior. Other information, not specific
to paint strippers but used to identify input parameters for the inhalation modeling, such as
interzonal air flows and air exchange rates, was obtained from peer-reviewed publications,
including US EPA (1995) and Matthews et al. (1989). Finally, in the case where no data were
available for fitting model-specific parameters, professional judgment was used and confirmed
with other sources of information where possible. This information has been identified in the
report along with the rationale for the chosen values.
Methodology. EPA estimated consumer inhalation exposures for both users and non-users to
NMP emitted during paint stripper application and associated scraping using MCCEM (US EPA,
2010b). MCCEM is ideally suited to this application, as it provides for modeling of incremental
source emissions, whereby a product is applied at a constant rate and the emission rate of the
chemical in each instantaneously applied segment is assumed to decline exponentially over
time. Depending on the type of applied product, either one or two exponential expressions
may be needed to characterize the declining emission rate. In this case, it was determined that
a double-exponential expression was appropriate (for more details, see Estimation of Emission
Profiles for Paint Removers/Strippers in Appendix D).
To select exposure scenarios for characterizing the consumer inhalation exposures, EPA
conducted a sensitivity analysis for optimizing the parameters used in the model for those that
had the most influence over the results of the assessment. Changing those values (i.e., by
varying combinations of parameters) enabled the generation of a wide range of plausible
exposure scenarios and increased the level of confidence in the model results. The methods
for, and results of, this sensitivity analysis are described immediately below.
Sensitivity Analysis Background. The types of factors that can be varied in the MCCEM model
include the following:
The configuration of the structure (residence in this case) being modeled, including
the number of zones, volume of each zone, airflow rates between each zone and
outdoors, and airflow rates between zones (i.e., interzonal airflow rates).
The quantity of NMP emitted from the applied product and the time-varying
emission rate, which are related to: (1) the type and area of surface being stripped;
(2) the type of application (e.g., brush-on vs. spray-on); and (3) the rate at which
the product is applied to the surface.
Locations during and after stripping of: (1) the user(s)the individual(s) applying
the product and (2) the non-user(s)other individual(s) present in the house who
are not involved in the paint-stripping activity and, by assumption, are located in a
house zone other than the one in which the paint-stripping activity is taking place.
Page 32
The sensitivity analysis was conducted using an approach that has been termed nominal range
sensitivity analysis (Frey and Patil, 2002). With this approach, an initial base case set of
model parameters is first defined, typically consisting of central tendency values (i.e.,
approximating average or median values) for each model parameter (input). Next, the inputs
are variedone at a timeand the model result (estimated average or peak concentrations to
which individuals are exposed) is noted. The index of sensitivity is the magnitude of change in
the model results, typically expressed as a percent change from that for the base case. Details
on this approach are in the Sensitivity Analysis for Inhalation Scenarios in Appendix D.
The time required to apply and scrape the paint stripper, including the wait time between
applying and scraping, is typically on the order of an hour, as determined by Abt (1992). The
model was run for a 24-hr period for the sensitivity analysis and the formal model runs to
capture all or most of the declining indoor-air concentrations following the product use event.
For this assessment, the relevant exposure measures include the maximum or peak TWA
concentrations for certain averaging periods (i.e., one minute, 10 minutes, 30 minutes, one
hour, four hours, and eight hours) in addition to the 24-hr TWA value. Illustrative time-varying
concentrations, to which the user and non-user could be exposed, based on a preliminary
model run, are shown in Figure 3-1 and Figure 3-2 ,along with the maximum TWA values and
the corresponding time periods for selected averaging times. For the sensitivity analysis, only
the maximum one-hr TWA along with the 24-hr TWA were used.
Page 33
Figure 3-1. Time-varying Consumer User Personal Concentration and Maximum TWA Values for
Selected Averaging Times.
Figure 3-2. Time-varying Consumer Non-user Personal Concentration and Maximum TWA Values for
Selected Averaging Times.
Page 34
The base case for the sensitivity analysis was formed using central (i.e., roughly equivalent to
average or mean) values for the various inputs, as follows:
House volume of 492 m3 (corresponds to 36 30 ft2, two-story house with an eightfoot ceiling)Workshop (area of product use) volume of 54 m3 (corresponds to 20
12 ft2 with an eight-foot ceiling) and an indoor-outdoor airflow rate of 68 m3/hr
(expected value for a room with multiple open windows)
Airflow rate of 197 m3/hr for the rest of the house (ROH), assuming windows
closed, corresponding to an air exchange rate of 0.45 air changes per hr (ACH)
Brush-on application with a target surface area of 10 ft2Applied product mass of

1,080 g (108 g/ft2) and emitted (released to indoor air)
NMP mass of 70.2 g, assuming an NMP weight fraction of 0.25 in the product and a
release fraction of 0.26
User located in workshop during application and scraping periods, but in ROH
during wait periods between applying/scraping and after completion of all
applying/scraping.
Sensitivity Analyses Results. The results of the sensitivity analyses for two exposure measures,
peak one- and 24-hr TWAs, are displayed in Figure 3-3 and Figure 3-4, respectively. For both
measures, and for both the user and the non-user, the change in model output for changing
chemical mass was 75 percent. This outcome is indicative of a linear and proportional
response. For the user, the model response was highly sensitive to location during the wait
period between applying and scraping (i.e., consumer stays in workshop versus moving to the
ROH), so that if the consumer stayed in the workshop during the wait period, inhalation
exposures likely would be higher. The model response was somewhat less sensitive to the ROH
air exchange rate with outdoor air (ROH ACH) for the non-user, but not for the user. This
outcome could be explained for the non-user as the rate of air exchange in the ROH is less of a
factor in inhalation exposure because initial exposures to the non-user were likely low. For the
user, initial exposures were higher and if the user moves to the ROH, the rate of air flow in the
ROH could reduce inhalation exposures under some conditions (i.e., high exchange rates).
Page 35
Figure 3-3. Model Sensitivity Results (Percent Change from Base-case Response) for Peak One-hr TWA
for Consumer User and Non-user.
Figure 3-4. Model Sensitivity Results (Percent Change from Base-case Response) for 24-hr TWA for
Consumer User and Non-user.
Results and Implications of Model Sensitivity Analyses. As a result of the model sensitivity
analyses, EPA concluded that the chosen modeling scenarios should include some variations in
each of the three factors (i.e., chemical mass, location, and ROH ACH); with greater model
sensitivity, it is more likely a wide range of plausible exposures can be estimated. The more
plausible the exposure scenarios, the more representative they are to real world conditions,
which aids with reducing the degree of uncertainty.
Description of Exposure Scenarios. Inhalation exposures to residential users and non-users
were determined. EPA developed eight exposure scenarios for the assessment, as summarized
in Table 3-5. The following factors were considered in developing the exposure scenarios:
The type of application (i.e., brush-on or spray-on), weight fraction of applied

product, application rate, surface area of object to be stripped, and emission rate of
Page 36
the chemical concern, which can affect the amount of NMP that ultimately is
released to the indoor environment;
The location where the product is applied, which relates to exposure factors such as
the room volume and its air exchange rate with outdoors;
The house volume and air exchange rate, for reasons similar to those for the
product use location; and
Precautionary behaviors such as opening windows in the application room and the
user leaving the application room during the use period, and related changes to the
air exchange rates and the proximity of the user to the source of NMP emissions.
Table 3-5. NMP Exposure Scenarios for the Characterizing Consumer Inhalation Exposure.
Case Description
Case ID
Type of
Application
Location of Product
Use
Concentration Characterizationa
Brush-on
Workshop
Central tendency
Brush-on
Workshop
User upper-end
Brush-on
Workshop
Non-user upper-end
Spray-on
Workshop
Central tendency
Spray-on
Workshop
User upper-end
Spray-on
Workshop
Non-user upper-end
Brush-on
Bathroom
Upper-end to bounding for user and nonuser, constrained by C sat = 1,300 mg/m3
Brush-on
Bathroom
Upper-end to bounding for user and nonuser, constrained by C sat = 640 mg/m3
Conditions obtained by varying the most sensitive parameters: NMP mass emitted; user location during the effect
or wait period; and the ROH air exchange rate with outdoors.
The primary distinctions among the eight cases, are in terms of type of application (i.e., brush
versus spray), location of product application (i.e., workshop versus bathroom), and values used
for other inputs including the NMP mass emitted, the users location during the use or wait
period, and the ROH air exchange rate with outdoors (i.e., central tendency 1 versus upperend 2). Of the eight scenarios listed in Table 3-5, two were considered central tendency for both
1
As noted in Section 2.3.1 (Individual Risk) of the US EPA (1992a) exposure assessment guidelines, Individual risk
descriptors will generally require the assessor to make estimates of high-end exposure, and sometimes additional
estimates (e.g., estimates of central tendency such as average or median exposure). For this assessment,
scenarios with central parameter values refer to a set of inputs that are expected to result in a central (i.e., near
the median) estimate of individual exposure.
2
As noted in US EPA (1992a), a high end exposure estimate is a plausible estimate of the individual exposure for
those persons at the upper end of an exposure distribution. The intent of this designation is to convey an estimate
of exposures in the upper range of the distribution, but to avoid estimates that are beyond the true distribution.
th
Conceptually, the high end of the distribution means above the 90 percentile of the population distribution, but
Page 37

the user and the non-user; two were developed to estimate upper-end concentrations for the
user; and two were developed to estimate upper-end concentrations primarily for the nonuser. Central-tendency values are exposure values expected to be near the average or median
for the range of exposure values; upper-end values are plausible exposure values from the
upper half of the range of expected exposure amounts. These descriptive exposure estimates
are generally required for risk assessments.
The final two Scenarios, 7 and 8, were developed to estimate NMP concentrations for the user
and non-user from use conditions similar to those reported by the Centers for Disease Control
and Prevention (CDC)/National Institute of Occupational Safety and Health (NIOSH)
occupational exposure case to a DCM paint stripper used on a bathtub (CDC, 2012). The
bathtub scenarios represent high product use in a confined (i.e., closed, poorly ventilated)
space. Selected parameter values for these scenarios (e.g., large surface area, small room size,
minimal ventilation, upper-end weight fraction, and low ROH ventilation) would increase
concentrations and exposures so that the combinations of parameter values would be expected
to result in upper-end to bounding 3 concentrations for the user and non-user and, as a result,
the concentrations could approach or exceed the vapor saturation concentration for NMP. The
only difference between Scenarios 7 and 8 is the assumed saturation concentration.
Further details of the exposure scenario inputs, including the parameter values for the NMP
saturation concentration and the procedures for representing the NMP emission behavior at
the saturation concentration, are discussed in the Inhalation Exposure Scenario Inputs section in
Appendix D.
Summary of Exposure Scenarios and Model Inputs. The exposure scenario inputs are as
follows: the amount of NMP released, stripping method, room of use volume and ventilation
characteristics, house volume and ventilation characteristics, the user location during the wait
period, and the non-user location. The inputs for all eight scenarios are summarized in Table 36, from which the major and subtle differences among the eight scenarios are shown. For
example, Scenarios 2 and 3, and their spray-application counterparts, Scenarios 5 and 6, are
targeted toward estimation of upper-end exposures for the user and non-user, respectively, by
changing the application amount, location of the user, and airflows.
not higher than the individual in the population who has the highest exposure. For this assessment, scenarios
labeled upper-end were modeled by selecting low- and high-end values for sensitive parameters. An upperend exposure estimate is above central tendency and may include the high end of the exposure distribution.
3
As noted in US EPA (1992a), an exposure above the distribution of actual exposures is termed 'bounding.'
Page 38

Table 3-6. NMP Consumer Paint Stripping Scenario Descriptions and Parameters.
Case
ID
NMP Released
Scenario
Weight
Fraction
Room of Use
Surface Area Application Release

a 2
2
Rate, g/ft Fraction
Treated ft
Stripping Method
House
User Location
Non-User
Volume, Ventilation/ Volume, ROH ACH, During Wait Location
b
3
3
-1
Period
m
ACH, 1/hr
m
hr
Brush-on Exposure Scenarios in Workshop

1
2
Central
0.25
10
(central) Coffee table
(central)
Upper-end 0.5
for user
(upperend)
Upper-end
for non-user
Central
108
0.26
25
Chest of
drawers
(upper-end)
1. Coffee table: 5-minute

54
application, 30-minute wait, and
(central)
10-minute scrape per application;
process repeated after completion
of first scraping
2. Scrapings removed from house
after last scraping
Open
492
0.45
windows /
(central) (central)
1.26
(Professional
judgment,
th
90
percentile)
3. Chest: 12.5/ 30/25 minutes per

application; process repeated after
completion of first scraping
4. Scrapings removed after last
scraping
ROH
Workshop
ROH
(entire
time)
0.18
ROH
(low-end)
Spray-on Exposure Scenarios in Workshop
0.44
10
(central) Coffee table
(central)
Upper-end 0.53
for user
(upperend)
Upper-end
for non-user
25
Chest of
drawers
(upper-end)
81
0.52
5. Coffee table: 2.5-minute

54
application, 30-minute wait, and
(central)
10-minute scrape per application;
process repeated after completion
of first scraping
after last scraping
Open
492
0.45
windows /
(central) (central)
1.26
(Professional
judgment,
th
90
percentile)
7. Chest: 6.25/ 30/25 minutes per

application; process repeated after
completion of first scraping
8. Scrapings removed after last
scraping
ROH
Workshop
0.18
ROH
(low-end)
Page 39
ROH
(entire
time)

Table 3-6. NMP Consumer Paint Stripping Scenario Descriptions and Parameters.
Case
ID
NMP Released
Scenario
Weight
Fraction
Room of Use
Surface Area Application Release

a 2
2
Rate, g/ft Fraction
Treated ft
Stripping Method
House
User Location
Non-User
Volume, Ventilation/ Volume, ROH ACH, During Wait Location
b
3
3
-1
Period
m
ACH, 1/hr
m
hr
Brush-on Exposure Scenario in Bathroom

7 and Upper-end 0.5
8
to bounding (upperfor user and end)
non-user
36
Bathtub
(maximum)
108
0.26
9. Bathtub: 18-minute application, 9c

30-minute wait, and 36-minute
(lowscrape per application; process
end)
repeated after completion of first
scraping
after last scraping
Window
492
0.18
ROH
closed, no
(central) (low-end)
exhaust fan/
d
0.18
(low-end)
ROH
(entire
time)
The surface area values were selected so that the calculated amount of product applied (g) corresponds approximately to the Abt (1992) survey results for amount of paint
th
2
th
stripper used (50 percentile value of 32 ounces or 1,000 g for the central surface area of 10 ft and ~80 percentile value of 80 ounces or 2,500 g for the upper-end surface
2
area of 25 ft ).
b
For all scenarios, the user is in the treatment room during the application and scraping times and in the ROH after the last scraping.
c
3
3
1 m for the vicinity of the tub (source cloud) and 8 m for the rest of the bathroom.
d
Because the user is working in close proximity to the target (bathtub) for an extended period, a third zone (source cloud) was created within the bathroom to represent the
NMP concentrations in the vicinity of the tub; this is a virtual zone, with no physical boundaries. The airflow rate between the cloud and the rest of the bathroom was based on
work by Matthews et al. (1989). (For more information, see discussion in Appendix C under Inhalation Exposure Scenario Inputs (Airflow Rates and Volumes.)
Page 40

Model Outputs and Exposure Calculations. To account for an individuals location at specific
times, MCCEM provides a detailed time series of zone-specific (i.e., house, workshop, and
bathroom) and personal concentrations. This model output is in the form of instantaneous
values at the end of consecutive one-minute time intervals for the entire duration of the model
run (i.e., 24 hrs). The model is responsive to changes in location of the user during the 24-hr
model run, Consequently, average concentrations to which the user and non-user were
exposed were calculated for successive one-minute time intervals by taking the average of the
instantaneous values at the beginning and end of each interval. A more detailed, mathematical
description of the calculations is provided in Appendix D in the Inhalation Model Outputs and
Exposure Calculations section).
Appendix D provides a summary of NMP exposure concentrations for the consumer user and
non-user of NMP-containing paint strippers. These concentrations were calculated by first
computing running averages and then taking the maximum of these averages. For example, for
the one-hour averaging period, the one-hour average concentration was calculated for each
one-minute start time during the 24-hr period (e.g., 0-60 minutes, 1-61 minutes, etc.), for which
the maximum of these averages is reported in Table 3-7. As the exposure averaging time
increases, the user to non-user exposure ratio decreases. For the one-minute averaging time,
the ratios of user to non-user highest concentrations are fairly consistent for central parameter
values and upper-end parameter values, ranging from 4:1 to 6:1 and approximately 16:1 for the
bathroom case. For longer averaging times, the maximum concentrations were quite similar
for the user and the non-user, with the single exception of the bathroom scenario.
The MCCEM Inhalation Modeling Case Summaries can be found in Appendix D summarizing
each of the eight scenarios modeled with MCCEM, including both model inputs and results.
Page 41

Table 3-7. Summary of Modeled NMP Concentrations to Which Consumer Users and Non-Users are Exposed, by Scenario.
Scenario
Individual
Maximum Values for Averaging Period, mg/m3 (ppm)

1 Minute
10 Minutes 30 Minutes
1 Hr
4 Hrs
8 Hrs
24 Hrs
1. Brush application in workshop,

central tendency scenario
User
33 (8.1)
30 (7.5)
15 (3.7)
13 (3.3)
6.6 (1.6)
3.8 (0.9)
1.3 (0.3)
Non-user
7.3 (1.8)
7.3 (1.8)
7.2 (1.8)
6.9 (1.7)
4.6 (1.1)
2.7 (0.7)
0.9 (0.2)

upper-end scenario for user
User
94 (23)
92 (23)
82 (20)
65 (16)
29 (7.1)
15 (3.8)
5.2 (1.3)
Non-user
15 (3.6)
14 (3.6)
14 (3.5)
14 (3.4)
9.1 (2.3)
5.5 (1.4)
1.9 (0.5)

upper-end scenario for non-user
User
200 (50)
180 (45)
150 (36)
98 (24)
59 (15)
38 (9.5)
15 (3.6)
Non-user
39 (9.7)
39 (9.7)
39 (9.6)
38 (9.4)
31 (7.7)
23 (5.7)
9.4 (2.3)
4. Spray application in workshop,

central tendency scenario
User
89 (22)
83 (20)
40 (9.9)
34 (8.3)
17 (4.2)
9.6 (2.4)
3.3 (0.8)
Non-user
19 (4.7)
19 (4.7)
19 (4.6)
18 (4.4)
12 (2.9)
7.1 (1.8)
2.4 (0.6)

upper-end scenario for user
User
150 (37)
148 (36)
130 (32)
100 (26)
45 (11)
24 (5.9)
8.1 (2.0)
Non-user
23 (5.7)
23 (5.7)
23 (5.6)
22 (5.3)
14 (3.5)
8.6 (2.1)
2.9 (0.7)

upper-end scenario for non-user
User
320 (78)
300 (74)
240 (60)
150 (38)
90 (22)
57 (14)
22 (5.4)
Non-user
62 (15)
61 (15)
61 (15)
60 (15)
49 (12)
36 (8.8)
14 (3.6)
830 (200)
520 (130)
290 (72)
110 (27)
7. Brush application in bathroom, User

upper-end to bounding for user and
Non-user
non-user; C sat = 1,300 mg/m3
8. Brush application in bathroom, User
upper-end to bounding for user and
Non-user
non-user; C sat = 640 mg/m3
1,300 (320) 1,300 (320) 1,300 (320)

110 (27)
110 (27)
110 (27)
110 (26)
91 (22)
72 (18)
33 (8.2)
640 (160)
640 (160)
640 (160)
580 (140)
310 (76)
170 (43)
64 (16)
65 (16)
65 (16)
64 (16)
63 (16)
54 (13)
43 (11)
20 (4.9)
Page 42

Limitations of the Consumer Inhalation Exposure Analysis. EPA conducted a literature search
to identify published studies and data to assess consumer inhalation exposures to NMP paint
stripping products. There was no relevant air monitoring data from consumer settings for
evaluating inhalation exposures from the use of NMP-containing paint strippers; to estimate air
concentrations for consumers, EPA identified published air monitoring data from one
occupational study conducted for EPA (US EPA, 1994b). Given the lack of measured data to
calculate inhalation exposures, consumer inhalation exposures were determined using a
modeling-based approach. EPAs MCCEM was used to predict concentrations in air to estimate
consumer inhalation exposures in various hypothetical consumer-use scenarios. MCCEM
requires input parameters including values for: product characteristics, use patterns, exposure
factors, and air concentrations to develop appropriate exposure scenarios. Published data was
used to determine product characteristics and use patterns, while other default information
was obtained from EPAs EFH for other model inputs (i.e., body weight, body part surface areas,
house volumes, and house ventilation rates). EPAs consumer inhalation exposure assessment
utilized a complex modeling approach which had a number of limitations: 1) Air concentration
data for NMP was obtained from an occupational study which may or may not closely resemble
residential workshop or consumer use settings and introduces uncertainty in the model results
and the overall risk assessment; 2) Data inputs also were derived from older studies introducing
uncertainty as to their relevance for current consumer settings where NMP paint strippers may
be used; and, 3) The assumptions used for the model exposure scenarios were hypothetical,
which may or may not reflect actual use conditions in consumer settings. Thus, the limited data
and variable results when used to extrapolate to consumer acute inhalation risk
characterization are uncertain.
Page 43
3.2. HUMAN HEALTH ASSESSMENT

This section discusses the hazard, dose-response, and risk analyses for NMP, and includes an
evaluation of the uncertainty and variability in the non-cancer risk estimates. As identified in
the problem formulation and scoping phase, the assessment calculated dermal and/or
inhalation risk estimates for three categories of individuals: (1) occupational users dermal and
inhalation; (2) ) occupational non-users who are being indirectly (inhalation only) exposed, (3)
residential users dermal and inhalation; and (4) residential non-users who are being indirectly
(inhalation only) exposed to NMP. The information is presented in the context of the exposure
pathways and exposure durations that are relevant to this human health risk assessment, which
are summarized in Table 3-8.
Table 3-8. Summary of Exposure Pathways, Toxic Endpoints and Risk Approach.
Exposure Pathwaya
Exposure
Receptors
Acute
Dermal
Acute
Inhalation
Chronic
Dermal
Chronic
Inhalation
Analytical Approach
Workers
Workers are likely to

be exposed repeatedly
to NMP. It was
assumed that a single
exposure is unlikely to
occur in workers.
Thus, acute risks were
not evaluated.
Workers are likely to Toxic endpoint:

be exposed
Developmental
repeatedly to NMP. toxicity
It was assumed that a Risk approach: MOE
single exposure is
unlikely to occur in
workers. Thus, acute
risks were not
evaluated.
Toxic endpoints:
Maternal and
developmental
toxicity
Risk approach:
MOE
Consumer
Users and
Non-Users
Toxic endpoint:
Developmental
toxicityb
Risk approach: MOE
Toxic endpoint:
Developmental
toxicityb
Risk approach:
Margin of Exposure
(MOE)
This exposure
pathway is not
expected to occur in
residents. Chronic
risks were not
evaluated.
This exposure
pathway is not
expected to occur in
residents. Chronic
risks were not
evaluated.
Residential exposures typically occur infrequently and over a period of a day (acute inhalation/dermal exposure),
while worker exposures are exposed daily on the job (chronic inhalation/dermal exposure).
b
Acute dermal and inhalation toxicity studies were not used because they typically measure lethality at high doses
and do not provide the level of analysis to assess non-effect levels from single exposures.
Note that the EPAs Integrated Risk Information System (IRIS) program has not developed a
toxicological review for NMP. In the absence of an IRIS assessment, the toxicological
information primarily was obtained from the OECDs SIDS assessment report for NMP (OECD,
2007).
Page 44

3.2.1. TOXICOKINETICS
NMP is well absorbed following inhalation (40 to 60 percent) and dermal (100 percent
depending on conditions) exposures. In rats, NMP is distributed throughout the organism and
eliminated mainly by hydroxylation to polar compounds, which are excreted via urine. About
80 percent of the administered dose is excreted as NMP and NMP metabolites within 24 hours.
The major metabolite is 5-hydroxy-N-methyl-2-pyrrolidone (5HNMP). Studies in humans show
that NMP is rapidly biotransformed by hydroxylation to 5HNMP, which is further oxidized to
N-methylsuccinimide (MSI); this intermediate is further hydroxylated to 2-hydroxy-N-methylsuccinimide (2HMSI). The excreted amounts of NMP metabolites in the urine after inhalation
or oral intake represented about 100 and 65 percent of the administered doses, respectively
(OECD, 2007).
Dermal absorption has been extensively studied as it typically poses the greatest potential for
human exposure. Due to its irritant properties, neat NMP is unlikely to remain in voluntary
contact with the skin for more than several hours. Dermal penetration through human skin has
been shown to be very rapid and the absorption rate is in the range of one to two mg/cm2-hr.
These values are two- to three-fold lower than those observed in the rat during the same
period. Prolonged exposures to neat NMP was shown to increase the permeability of the skin.
Skin penetration can also be affected by solvents and to a lesser extent by the state of
occlusion. Water inhibits dermal absorption while other organic solvents (e.g., d-limonene) can
increase it. The dermal penetration of 10 percent NMP in water is 100-fold lower than that of
neat NMP, while dilution of NMP with d-limonene can increase the absorption of NMP by as
much as 10-fold. The dermal absorption of neat NMP under different conditions indicated that
dermal absorption one hour post-exposure was greatest under unoccluded conditions
(69 percent), followed by semi-occluded (57 percent) and occluded (50 percent) conditions
(OECD, 2007).
Dermal uptake of airborne NMP has been reported in toxicokinetic studies in humans. Bader et
al. (2008) exposed volunteers for eight hours to 80 mg/m3 of NMP. Exposure was whole body
or dermal-only. Excretion of NMP and metabolites was used to estimate absorption under
different conditions. The authors found that dermal-only exposures resulted in the excretion of
71 mg NMP equivalents whereas whole-body exposures in resting individuals resulted in the
excretion of 169 mg NMP equivalents. Under a moderate workload, the excretion increased to
238 mg NMP equivalents. Thus, the dermal absorption component of exposure from the air
will be in the range of 30 to 42 percent under whole-body exposure conditions to vapor.
It is interesting to note that there is evidence to support that absorption and effect are very
similar by oral and dermal routes. Oral LD 50 values were 4,150, 3,914 and 3,605 mg/kg in rats
(Ansell and Fowler, 1988; Bartsch et al., 1976; BASF AG, 1963; as cited in OECD, 2007,
respectively) and 7,725 and 4,050 mg/kg in mice (Bartsch et al., 1976; Weisbrod and Seyring,
1980; Weisbrod, 1981; as cited in OECD, 2007) to dermal dose levels.
Page 45

3.2.2. Hazard Identification
Oral exposures to NMP-containing products are expected to be negligible and were not
evaluated in this assessment. However, EPA has concerns for exposures to NMP when it is used
as a paint stripper because it is rapidly absorbed through skin and may be inhaled as a vapor in
confined spaces. Below is a summary of the toxicological information that supported the
decision to analyze dermal and inhalation exposures as the most relevant pathways. Detailed
summarizes of the available toxicology studies are provided in Appendix E.
NMP is well absorbed following dermal (< 100 percent) and inhalation (40 to 60 percent)
exposures. The hazards associated with exposure by each of these routes have been evaluated
in a number of different repeated-dose studies. A brief description of the studies relevant to
chronic and acute dermal and inhalation exposure scenarios is provided below.
Dermal. Dermal repeated dose toxicity studies in rats and rabbits have shown that
developmental toxicity is the endpoint of concern; rats are more sensitive than rabbits. In a
developmental toxicity study in rats administered NMP at dose levels of 75, 237, and 750
mg/kg, a NOAEL for maternal and developmental toxicity of 237 mg/kg was identified (Becci et
al., 1981; Becci et al., 1982; FDRL, 1979; E.I. Dupont de Nemours & Co., 1992; as cited in OECD,
2007). At the limit dose, dams (i.e. mothers) experienced a 17 percent decrease in body
weight; developmental toxicity was expressed as fewer live fetuses, increased resorption rate,
reduced fetal body weight, and skeletal abnormalities. In a subchronic dermal toxicity study in
rabbits administered NMP at dose levels of 413, 826, and 1,653 mg/kg, a NOAEL for systemic
toxicity of 826 mg/kg was identified (GAF Corp., 1986; Industrial Biology Research and Testing
Laboratories., 1963; as cited in OECD, 2007). One rabbit died in the limit dose group; no
systemic toxicity to clinical, hematological, or histopathological measures was seen in the
remaining rabbits in this dose group. No dermal subchronic studies in rats were identified.
Inhalation. Whole-body inhalation studies with NMP as a vapor have shown marginal
developmental toxicity in rats and rabbits, as the only endpoint of toxicological concern. As
with dermal exposures, rats were the more sensitive species. In a developmental toxicity study,
the no-observed-adverse-effect level (NOAEL) for decreased maternal and fetal body weight
was 60 ppm (122 mg/m3) and 120 ppm (243 mg/m3), respectively (Saillenfait et al., 2001;
Saillenfait et al., 2003; as cited in OECD, 2007). No chronic toxicity was observed in a two-year
study in rats exposed to vapor concentrations up to 100 ppm (405 mg/m3) (E.I. Dupont de
Nemours & Co., 1990; Lee et al., 1987; WHO, 1986; Kennedy, 2008; as cited in OECD, 2007). No
effects were observed in additional rat studies that evaluated reproductive toxicity,
neurotoxicity, etc., when NMP was administered up to saturation. In contrast, NMP as an
aerosol has been shown to cause overt acute and subchronic toxicity in rats. A four-hour
exposure to aerosolized NMP at concentrations of 4,800 mg/m3 and 8,800 mg/m3, was lethal to
four of six rats and six of six rats, respectfully (E.I. du Pont de Nemours., 1988; as cited in OECD,
2007). In a 28-day study, eight of thirty rats exposed to aerosolized NMP at 740 mg/m3 died
within nine days after the cessation of exposures and five rats were sacrificed in extremis (US
EPA, 1989; E.I. Dupont de Nemours & Co., 1991).
Page 46
The differences between the effects observed with NMP as a vapor versus an aerosol may be
explained from the higher internal dose that animals receive with aerosolized NMP. In the
inhalation chamber, the amount of vapors and aerosols is dependent on the airborne NMP
concentration, temperature, and humidity in the inhalation chamber. When NMP ambient
concentrations become saturated, it is expected that the exposure has an inhalation
component to NMP vapors and a dermal component to NMP aerosols. This notion was
discussed by the OECD (2007), which stated:
The maximum vapor phase at room temperature is 1,286 mg/m3 (315 ppm) in
dry air (0% relative humidity), 525 mg/m3 (128 ppm) at normal animal room
humidity (50% relative humidity) and 0 mg/m3 (0 ppm) in humidity saturated air
(100% relative humidity BASF AG, 1995c, b, a, 1989, 1992). Thus, the vapor
saturation of NMP under normal conditions is considered to be in the range of
480-640 mg/m3 (120-160 ppm) depending on humidity and temperature (BASF
AG, 1995b).
To summarize, the available studies on NMP have shown five primary points about the hazard
of this compound: 1) NMP is well absorbed following dermal and inhalation exposures; 2) rats
are more sensitive to NMP than rabbits; 3) dermal exposures lead to the greatest hazard; 4)
inhalation exposures result in marginal toxicological effects up to saturation (i.e., aerosol
formation); and 5) developmental toxicity is the endpoint of concern for dermal and inhalation
exposures.
3.2.3. Dose-Response Assessment
This section presents the dose-response assessment conducted by EPA for the non-cancer
health effects associated with dermal and inhalation exposures to NMP. Data from the
hazard/toxicological studies summarized in Appendix E were evaluated to determine NMPs
dose-response relationships, which were used to inform the estimation of risks for specific
exposure scenarios.
When NMP is used in paint stripping applications, exposures are expected to occur
predominantly by the dermal route when proper personal protective equipment (e.g., gloves)
are not used. Inhalation exposures to NMP also may occur, primarily to NMP as a vapor, when
used in confined spaces. Therefore, EPA developed dose-response assessments from dermal
toxicity studies and from inhalation toxicity studies where NMP was administered primarily as a
vapor.
In order to select the most appropriate key studies for this analysis, the relative merits of the
animal studies were evaluated with respect to: (1) their adequacy to the exposure pathways
(i.e., dermal and inhalation) and exposure durations (i.e., acute and chronic) under
consideration; (2) the exposure levels at which adverse effects were observed; and (3) the
species susceptibility to NMP exposure. Also, EPA focused on the most sensitive effects (e.g.,
Page 47

developmental effects) reported in the toxicological literature that are relevant to exposure
scenarios for paint stripping.
The selected key studies provided the dose-response information for the selection of points of
departure (PODs). EPA defines a POD as the dose-response point that marks the beginning of a
low-dose extrapolation. This point can be the lower bound on the dose for an estimated
incidence or a change in response level from a dose-response model (e.g., benchmark dose or
BMD), a NOAEL, or a lowest-observed-adverse-effect level (LOAEL) for an observed incidence,
or a change in level of response. PODs were adjusted as appropriate to conform to the
exposure scenarios derived in Chapter 2.
3.2.4. Key Studies, PODs, and Levels of Concern for the Dermal Pathway
Acute Dermal Exposures. The adult acute dermal toxicity studies were not used for the acute
dermal POD because no acute toxic effects or lethality were observed at dose levels up to 5,000
mg/kg (Clark et al., 1984; Weisbrod, 1981; Weisbrod and Seyring, 1980; as cited in OECD, 2007).
This toxicological finding is relevant to women of childbearing age, including pregnant woman,
who may be directly or indirectly exposed to NMP from single-event paint stripping uses.
Subchronic Dermal Exposures. In a four week subchronic repeated dose study, mild irritation
was noted in rabbits in all treatment groups; a NOAEL of 826 mg/kg was reported for systemic
toxicity (GAF Corp., 1986; Industrial Biology Research and Testing Laboratories., 1963; as cited
in OECD, 2007). The rabbit subchronic study reported a NOAEL of 826 mg/kg for systemic
toxicity. This value was several times higher than the reported NOAELs of 237 mg/kg and 300
mg/kg for developmental toxicity in the rat and rabbit, respectively (Becci et al., 1981; Becci et
al., 1982; FDRL, 1979; E.I. Dupont de Nemours & Co., 1992; as cited in OECD, 2007).
Rationale for Study and Endpoint Selection for Acute and Chronic PODs. Developmental
studies involve multiple exposures on the order of 10-15 days; however, they are relevant to
single exposures because developmental effects may result from a single exposure at a
developmentally critical period (Van Raaij et al., 2003; US EPA, 1991b; Davis et al., 2009).
Therefore, the dermal developmental studies represented the most relevant endpoint for
estimating the acute risks for residential scenarios.
This approach is supported by Van Raaij et al. (2003). These authors evaluated several
developmental toxicity studies that reported NOAELs and LOAELs for single day exposures or
repeated exposures over the developmental period. An examination of the fetal body weight
loss parameter (n = 12 studies) showed that the ratio of the single-dose to repeated-dose
NOAELs was less than four-fold for nine of the 12 studies.
The dermal developmental studies of NMP exposure reported NOAELs that were several times
lower than the NOAEL reported in the rabbit subchronic study. Therefore, because these were
more sensitive indicators of effect, the developmental studies were also used for developing
the chronic POD.
Page 48
NOAEL HED approach for Acute Dermal POD. The rat NOAEL of 237 mg/kg was converted to a
human equivalent dose (HED) of 56 mg/kg using the BW correction assuming a rat body
weight of 0.25 kg and a human body weight of 80 kg (i.e., NOAEL HED = 237 mg/kg [0.25 kg-0.25
80 kg-0.25]) (US EPA, 2011d). Note that the correction also was made to the rabbit NOAEL, but
the adjusted rabbit value (i.e., NOAEL HED = 70 mg/kg) was higher than the one obtained for the
rat NOAEL.
NOAEL HED approach for Chronic Dermal POD. Developmental effects may occur in response to
single or repeated exposures to NMP, particularly during specific windows of susceptibility
during pregnancy and affect the developing fetus. Thus, EPA used the acute dermal POD (56
mg/kg) to evaluate the risks of chronic dermal exposures to NMP. The POD for this toxicological
finding is relevant to women of childbearing age, including pregnant woman, who may be
directly or indirectly exposed to NMP from repeated paint stripping uses.
3.2.5. Key Studies, PODs, and Levels of Concern for the Inhalation Pathway
Acute Inhalation Exposures. NMP has a comprehensive set of inhalation toxicity studies that
comprise acute, developmental, reproductive, and subchronic studies as well as a two-year
carcinogenicity study (Appendix E). In this spectrum of tests, the acute four-hour and
developmental inhalation studies were the most relevant to assess single exposure (acute)
PODs.
The acute exposure studies demonstrated lethal toxicity at doses much higher than seen in the
developmental toxicity studies and involved exposures to aerosolized NMP. For example, no
animals died when exposed to NMP for four hrs at 5,100 mg/m3 (head-nose exposure) (BASF
AG, 1988a; as cited in OECD, 2007). Rats exposed to a range of NMP concentrations (3,100 to
4,800 or 5,000 to 8,800 mg/m3; head-nose exposure) only died when exposed to 4,800 or 8,800
mg/m3 (i.e., four of six and six of six animals, respectively) (E.I. du Pont de Nemours., 1988; as
cited in OECD, 2007). The lowest exposure tested in these studies was 3,100 mg/m3 for four
hrs. Because effects were seen in developmental toxicity studies at much lower exposures to
NMP as a vapor, the four-hr acute studies were not used for the acute inhalation POD for
residential users and non-users.
Rational for Study and Endpoint Selection for Acute PODs. Developmental inhalation studies
have been performed with rats and rabbits. Due to the greater susceptibility of rats, the NOAEL
for developmental toxicity reported by Saillenfait et al. (2001); Saillenfait et al. (2003) (as cited
in OECD, 2007) was used in this assessment. Using these data, acute PODs were derived using
two approaches. In the first approach, benchmark dose modeling (BMD) was performed to
derive a benchmark concentration level (BMCL). This value was converted to a human
equivalent concentration (HEC) (i.e., BMCL HEC approach). In the second approach, a NOAEL was
used as the POD (i.e., NOAEL or default approach). A physiologically based pharmacokinetic
(PBPK) approach also was considered, but not carried forward in the assessment because of
model limitations, as discussed below. Currently, the BMD approach is the preferred approach
Page 49

for representing the PODs since its makes estimates based upon the entire doseresponse
curve with its variability and not based on a single nominal dose group in a given study as is the
case in the NOAEL/LOAEL approach. A summary of these approaches is described below.
BMCL HEC approach for Inhalation Acute POD. EPA performed benchmark dose (BMD)
modeling on the fetal body weight data from the Saillenfait et al. (2001) and Saillenfait et al.
(2003) studies (as cited in OECD, 2007). A benchmark concentration level (BMCL) with a
benchmark response of five percent for this endpoint was used to derive a six-hour BMCL 05 of
302 mg/m3 (Appendix F; Table F-2). The six-hr BMCL 05 was adjusted to account for dosimetric
extrapolation from animals to humans according to EPAs guidance (US EPA, 2011a, 2009,
1994a). The adjustments consisted of using blood:air partition coefficients in animals and
humans to estimate a dosimetry adjustment factor (DAF), which was used to calculate a human
equivalent concentration (HEC). A default value of one was used for the DAF because the
blood:air partition coefficients were unknown. Therefore, the six-hr BMCL HEC of 302 mg/m3
was used as the acute POD for informing risk determinations for inhalation scenarios in
residential settings.
NOAEL Approach for Inhalation Acute POD. EPA selected the NOAEL of 243 mg/m3 for
decreased fetal body weight from the (Saillenfait et al., 2001; Saillenfait et al., 2003) studies (as
cited in OECD, 2007) as an acute POD. Other rat developmental studies, while not used for
development of the POD, were supportive (Hass et al., 1994; Solomon et al., 1995). This
approach was presented for comparison with the BMCL HEC approach, but it was not used for
informing risk determinations.
PBPK Model for Extrapolation. Poet et al. (2010) developed a PBPK model to reduce
uncertainty associated with extrapolating findings from animal toxicity studies to humans.
These authors initially developed the model for adult non-pregnant rats and then extrapolated
it to pregnancy. EPA evaluated this model 4 and determined that it contained limitations that
precluded its utility for quantitative use in deriving a POD for this risk assessment (Appendix G).
Chronic Inhalation Exposures. A comprehensive set of inhalation studies were available for
NMP, which included: reproductive toxicity studies, developmental toxicity studies, subchronic
toxicity studies, and a chronic toxicity study. Each of these studies was considered for deriving
the chronic exposure PODs. Chronic PODs were developed for various toxicological endpoints
and the rationale for their selection is discussed below.
Rational for Study and Endpoint Selection for Chronic PODs. Based on the toxicological studies
performed on NMP, developmental toxicity has been shown to be the endpoint of concern.
Because of this, EPA has concerns about chronic exposures of female workers of child bearing
age, including pregnant females, to NMP-containing paint strippers. Therefore, the Saillenfait
et al. studies (Saillenfait et al., 2001; Saillenfait et al., 2003; as cited in OECD, 2007) were used
The model titled NMP PBPK Model.zip is available at http://www.epa.gov/oppt/existingchemicals/pubs/workplans.html
Page 50

for deriving chronic PODs using a BMCL HEC approach for fetal toxicity and a NOAEL approach for
maternal and fetal toxicity.
BMCL HEC Approach for Inhalation Chronic POD. The six-hr BMCL HEC of 302 mg/m3 (BMCL HEC
approach) that was derived from the Saillenfait et al. studies (Saillenfait et al., 2001; Saillenfait
et al., 2003; as cited in OECD, 2007) was used as the chronic POD for informing risk
determinations.
NOAEL Approach for Inhalation Chronic POD. The maternal and fetal chronic PODs were based
on the NOAELs of 122 mg/m3 and 243 mg/m3, respectively, for decreased body weight
(Saillenfait et al., 2001; Saillenfait et al., 2003; as cited in OECD, 2007). These values derived
from the NOAEL/LOAEL approach were used for comparison purposes only and are not the
preferred risk determinations.
3.3. HUMAN HEALTH RISK CHARACTERIZATION

Time Scaling of Chronic PODs. Habers rule (C x t = k) was used to time scale all of the chronic
inhalation PODs (see Table 3-9). Chronic PODs correspond to six- hr/day exposures, but the
human exposure estimates (exposure section) were expressed as ADCs, which are continuous
24-hr/day exposures for a working lifetime (40 yrs).
Table 3-9. Time Scaling of Chronic POD Values.
Toxicological
Effect
POD and
Exposure Duration
Scaled POD values for

24 Hrs/day, 7 Days/Weeka
Fetal toxicity (BMCL HEC )
302 mg/m3
6 hrs/day, 7 days/week
76b mg/m3
Maternal toxicity (NOAEL)
122 mg/m3
31c mg/m3
Fetal toxicity (NOAEL)
243 mg/m3
61c mg/m3
Scaled value = concentration (mg/m3) days (6 hrs/24 hrs)

POD used in risk characterization.
c
PODs shown for comparison with the BMCL HEC approach.
b
This section provides an evaluation of the different occupational and consumer exposure
scenarios and develops margins of exposure (MOEs) using the PODs derived in the previous
section. The resulting MOEs were used for informing risk determinations, as discussed below.
Page 51
3.3.1. Risk Estimation Approach for Acute and Chronic Exposures

To estimate non-cancer acute and chronic risks, EPA calculated MOEs. These values represent
the ratio of the scaled POD to the exposure. This approach allows the reader to better
understand the toxicological basis for the risks and the uncertainties that went into the risk
determinations. MOEs were compared to benchmark MOE levels to determine whether
potential risks of concern were present for the different exposure scenarios. Benchmark MOE s
were established based on the composite value of uncertainty factors (UFs) that addressed
intraspecies uncertainty (UF H ; i.e., human to human) and interspecies uncertainty (UF A ; i.e.,
animal to human). A default value of 10 is typically used for each UF (i.e., UF H = 10; UF A = 10).
The default value of 10 is derived from the composite value of 3.16 for toxicokinetics (TK) and
3.16 for toxicodynamics (TD) according to the equation: 3.16 [TK] 3.16 [TD] = 10. For the
NOAEL HED and BMCL HEC PODs, the TK component of the UF A was reduced to 1, based on Agency
guidance (US EPA, 2011a,d) applying allometric scaling of BW3/4. The resulting UF A of ~3
accounts for TD uncertainty. Therefore, if an MOE was less than a benchmark of 30 (i.e., 10
[UF H ] 3 [UF A ]), a potential risk of concern was identified. As a comparison, a default
benchmark of 100 (i.e., 10 [UF H ] 10 [UF A ]) was presented for PODs based on the NOAEL
approach. Table 3-10 depicts a summary of the dose-response data (e.g., POD, toxicological
effects, levels of concern) and risk approaches EPA used in NMPs risk assessment. MOEs
greater than the benchmark levels were viewed as negligible risks of concern.
Page 52
Table 3-10. Dose-Response Values and Risk Approaches for NMPs Human Health Risk Assessment.
Exposure Scenario
Concentration(s) and Time

Duration(s) Used in Risk
Assessment
Total UFs
Toxicological Endpoint
Non-Cancer Acute Dermal Risks

Increased resorption, fewer live fetuses,
POD of 56c mg/kg (NOAEL HED
UF H =10, UF A =3
Residential usersa
reduced body weight, skeletal
approach)
Total UF=30
abnormalities
Non-Cancer Acute Inhalation Risks POD Scaled to 4 Hours Exposure
Scaled POD of 453c mg/m3 for 4
UF H =10, UF A =3
hours exposure from Saillenfait
Total UF=30
et al. (2003) (BMCL HEC approach)
Residential usersa and
Fetal body weight decrease
Scaled POD of 65d mg/m3 for 4
non-usersb
hours exposure from the
UF H =10, UF A =3
Saillenfait et al. (2003) (NOAEL or
Total UF=30
Default approach)
Non-Cancer Chronic Dermal Risks
Increased resorption, fewer live fetuses,
POD of 56c mg/kg (NOAEL HED
UF H =10, UF A =3
Occupational workers
reduced body weight, skeletal
approach)
Total UF=30
abnormalities
Non-Cancer Chronic Inhalation Risks POD Scaled to 24 Hours/Day, 7 Days/Week to Correspond to ADC
Scaled POD of 76c mg/m3
BMCL of 5% reduction in fetal body
UF H =10, UF A =3
(BMCL HEC approach)
weight
Total UF=30
Occupational workers
d
3
UF H =10, UF A =3
Scaled POD of 31 mg/m
Decrease in maternal body weight gain
Total UF=30
(Default approach)
Risk
Estimation
Approach
MOE
MOE
MOE
MOE
MOE
Residential users are those who would be working directly with the NMP-containing paint stripper in a home workshop or a bathroom.
Residential non-users would be individuals who would be in the ROH at the time of the paint stripper application.
c
POD used for informing risk determinations.
d
PODs shown for comparison with the BMCL HEC approach.
b
Page 53
3.3.2. Risk Estimates for Non-Cancer Acute Dermal Exposures in a Residential Setting
Table 3-11 shows the acute dermal MOEs for consumers using NMP-based paint strippers
without personal protective equipment (i.e., gloves) in the home. The analysis does not
evaluate risks to other residential occupants because the skin of non-users is not expected to
be in contact with the product.
The exposure analysis assumed that a defined surface area of the residential/consumer users
skin was exposed to a thin film of the product. The thin-film modeling approach also assumed
exposure to an adult individual of 80-kg for one time only (i.e., one event in a single day).
Central and high-end exposure scenarios were estimated for brush-on or spray-on applications.
Acute dermal MOEs ranged from 0.5 to 1.0. For all of the modeled scenarios, the MOEs were
below the benchmark of 30, indicating potential risks of concern for consumers using NMPbased paint strippers without personal protective equipment.
Table 3-11. Acute MOEs for Residential Users and Non-Users of NMP-Based Paint Strippers Dermal
Exposures.
Case ID
Scenario Description
Acute Dermal Exposure,

ADR dermal
(mg/kg-day)
Acute Dermal MOEs

POD = 56 mg/kg-day;
Level of Concern MOE <30
Brush-on, central estimate
50
1.1a
Brush-on, high-end estimate
100
0.56
Spray-on, central estimate
89
0.63
Spray-on, high-end estimate
110
0.51
Bolded values are below the MOE and indicate potential risks of concern.
3.3.3. Risk Estimates for Non-Cancer Acute Inhalation Exposures in a Residential

Setting
Table 3-12 shows the acute four-hour inhalation MOEs for various do-it-yourself (DIY) exposure
scenarios. These hypothetical (i.e., what if) scenarios assumed brush or spray applications in
either a workshop or a bathroom. The user location during application was varied in the
exposure scenarios. Scenarios 2 and 5 assumed that the user remained in the workshop after
applying NMP. Scenarios 1, 3, 4, 6, 7, and 8 assumed that the user went to the ROH after
applying NMP.
MOEs for inhalation exposures were estimated for both residential users and non-users. The
MOEs calculated by the BMCL HEC approach ranged from 0.87 to 69 and from five to 98 for users
and non-users, respectively. For scenario 1, the MOEs for users and non-users were above the
benchmark of 30, indicating negligible risks of concern. For scenarios 2, 4, and 5, the MOEs for
users that were below the benchmark of 30, indicating potential risks of concern for users.
Page 54

Scenarios 3, 6, 7, and 8 resulted in MOEs for users and non-users that were below the
benchmark of 30, indicating risks of concern for both users and non-users.
For Scenarios 1 to 6 (workshop), MOEs calculated by the NOAEL approach ranged from 0.1 to
9.8 and from 0.7 to 14 for users and non-users, respectively. MOEs for users and non-users of
the bathroom scenarios (7 and 8) ranged from 0.7 to 1.2 and 0.1 to 0.2, respectively. These
MOEs were below the benchmark of 30, indicating potential risks of concern for both users and
non-users.
Page 55

Table 3-12. Acute MOEs for Residential Users and Non-Users of NMP-Based Paint Strippers Inhalation
Exposures.
Maximum Values
for 4-hr
Averaging Period,
(mg/m3)
MOEs
BMCL HEC
APPROACH
Scaled POD=
453 mg/m3
Level of Concern
MOE <30
MOEs
Default
APPROACH
Scaled POD=
65 mg/m3
Level of Concern
MOE <30
User
6.6
69
9.8a
Non-User
4.6
98
14
2. Brush application in
User
workshop, upper-end scenario Non-User
for user
29
16
2.2
9.1
50
7.1
User
for non-user
59
7.7
1.1
31
15
2.1
4. Spray application in
workshop, central tendency
scenario
User
17
27
3.8
Non-User
12
38
5.4
User
for user
45
10
1.4
14
32
4.6
User
for non-user
90
0.7
49
9.2
1.3
bathroom, upper-end to
bounding for user and nonuser; C sat = 1,300 mg/m3
User
520
0.87
0.1
Non-User
91
0.7
bounding for user and nonuser; C sat = 640 mg/m3
User
310
1.5
0.2
Non-User
54
8.4
1.2
Scenario
workshop, central tendency
scenario
Individual
Page 56
3.3.4. Risk Estimates for Non-Cancer Chronic Dermal Exposures to Workers

Table 3-13 shows the chronic dermal MOEs for workers when applying NMP-based paint
strippers. Note, these values were calculated with the assumption that appropriate gloves
were not worn.
Dermal exposures were estimated using a conservative modeling approach that assumed
exposure to liquid NMP, maximum skin absorption (100 percent), and a stripper content of
100 weight percent of NMP. The potential dose rates ranged from 590 to 1,800 mg and
corresponded to exposure to liquid NMP per day. Body weight-normalized potential dose rates
ranged from 7.4 to 22 mg NMP/kg/day. Chronic dermal MOEs ranged from 2.5 to 7.6 and were
below the benchmark MOE of 30, indicating potential risks of concern to workers when
applying NMP-based paint strippers.
Table 3-13. Chronic MOEs for Worker Dermal Exposures.
Industry
Any workplace setting (no gloves)
a
Chronic Dermal Exposure,

mg/kg-day
MOE
POD = 56 mg/kg-day
Level of Concern MOE <30
7.4-22
7.6-2.5a
3.3.5. Risk Estimates for Non-Cancer Chronic Inhalation Exposures to Workers

The exposure assessment examined the occupational literature and looked for air monitoring
data in small shop operations expected to use NMP-based paint strippers. Air concentrations
reported as eight-hr TWAs were used to estimate ADCs used in the MOE calculations. The
availability of eight-hr TWA exposures was limited and only available for industries using NMPbased paint strippers in graffiti removal.
Table 3-14 presents the calculated MOEs for workers in the graffiti removal industry. The MOEs
were as high as 10,857 if the lower end of the air concentrations were used, and as low as 72
when the high end of the air concentration was used with the BMCL HEC approach. These values
exceed the benchmark MOE of 30, indicating negligible risks of concern for workers. In
comparison, the NOAEL approaches resulted in MOEs below the respective benchmark levels
for high concentrations of NMP, indicating potential risks of concern. It should be noted that
EPA does not consider the MOEs based on the BMCL HEC approach reliable due to the limited
amount of exposure data from which these values were derived.
Page 57

Table 3-14. Chronic MOEs for Worker Inhalation Exposures.
Exposure
Industry
Graffiti
removal
a
ADC
(mg/m3)
0.007-1.0
Ranges of MOEs
Systemic Toxicity Maternal Toxicity
(Default approach) (Default approach)
POD = 30 mg/m3
POD = 72 mg/m3
Level of Concern Level of Concern
MOE <30
MOE <30
10,286-72a
4,286-30
Fetal Toxicity
(BMCL HEC
approach)
POD = 76 mg/m3
Level of Concern
MOE <30
Fetal Toxicity
(Default
approach)
POD = 61
mg/m3 Level
of Concern
MOE <30
10,857-76
8,714-61
3.4. DISCUSSION OF KEY SOURCES OF UNCERTAINTY AND DATA LIMITATIONS

3.4.1. Key Uncertainties and Data Limitations for Occupational Exposure Estimates
Dermal Exposures. The EPA dermal exposure model used in this assessment presents a
hypothetical estimate of dermal exposure to a liquid by assuming that appropriate gloves were
not worn to reduce exposure. It is important to note that the EPA dermal exposure model uses
a default value of one exposure event per worker per day. Chemicals with high skin absorption
can cause variations of surface densities, which can also be impacted by the number of
exposure events per worker per day. However, since NMP is corrosive, the default assumption
of one exposure event per day was considered appropriate because it may address accidental
exposures that may occur in the workplace.
Inhalation Exposures.
Limitations of the inhalation exposure data also introduce uncertainties into the exposure
summary (Table 3-3). The principal limitation of the exposure data is the uncertainty in the
representativeness of the data. EPA identified a limited number of exposure studies that
provided with data on the number of facilities, job sites, or residences where NMP was used.
These studies primarily focused on single sites. This small sampling pool introduces uncertainty
into the observed data because it is unclear how representative the data are to all sites and for
all workers within the particular end-use application across the US. Differences in work
practices and engineering controls across sites can introduce variability and limit the
representativeness of any one site with regard to all sites. The impact of these uncertainties
precluded EPA from describing actual exposure distributions. Central tendency and high-end
exposures may or may not lie within the range of exposures estimated for this assessment.
The age of the identified exposure studies also adds some uncertainty. Most of the exposure
studies were conducted in the 1990s. Some references have suggested a trend to reduce the
use of DCM in paint stripping products; NMP has been suggested as an alternative paint
Page 58

stripping component to DCM. If accurate, this change could have a direct impact on the
frequency of exposure and the number of workers exposed to NMP. In the absence of actual
exposure distributions, the reliability of the calculated MOEs for workers is unclear.
The assumed values for several parameters for use in the equation to estimate ADCs introduce
some additional uncertainties. Exposure frequencies were assumed to be 250 days/yr (i.e.,
every work day), and working years per lifetime was assumed as 40 years, which seems likely to
be a high-end estimate. The impact of these uncertainties is that some exposures in this
assessment will be overestimated for workers who are not exposed each work day or for a full
shift for their full working career.
3.4.2. Uncertainties in the Residential Exposure Assessment
The consumer dermal exposure scenarios developed for this assessment were hypothetical
based on uncertainties in the modeling methods and input parameters. As described in US EPA
(1992a), this approach answered questions about individual exposures, but did not provide
information about how likely the combination of values that were used might be in the actual
population. According to US EPA (1996), hypothetical estimates answer the question, What is
the exposure if the assumptions are valid?
The consumer inhalation exposure assessment is composed of modeled exposure scenarios
whose inputs were based on experimental data, survey information, and a number of
assumptions with varying degrees of uncertainty. The results were characterized as either
plausible estimates of individual exposure (e.g., central tendency) or possibly greater than the
distribution of actual exposures (e.g., bounding).
The biases of the uncertainties identified below are not known, so differences in the parameters
that were discussed could result in either larger or smaller exposure estimates.
Further discussion of uncertainties as they relate specifically to the dermal and inhalation
assessments is provided in the subsections that follow.
Dermal Exposure. One of the major uncertainties in the dermal model is the assumption that
one thin film per exposure event gets on the skin. As stated in US EPA (1996), the number of
times per exposure event that a person contacts the paint remover product is unknown. It also
is assumed that protective gloves are not worn. This assumption was considered relevant
because consumers, unlike workers, may not have the experience with taking the necessary
precautions (i.e., wearing appropriate gloves) to avoid dermal exposures to corrosive
compounds like NMP.
Additionally, there is uncertainty in the film thickness value used, and there are questions
about the uniformity of films associated with product usage. The only film thickness value
available that is specific to paint strippers (0.03 cm) is based on professional judgment from a
Klean Strip chemist (US EPA, 1996). No details are available regarding the derivation of this
Page 59

value. Limited film thickness values are available in the EFH for a variety of liquids (e.g., mineral
oil, cooking oil, bath oil, bath oil/water, water, and water/ethanol), but they were not relevant
to paint stripper products and were based on a limited number of observations. For
comparison purposes only, the film thickness for water (50 percent)/ethanol (50 percent) on
skin was estimated to be 0.0065 cm after full immersion of the hand into the liquid with no
wiping.
Another case of parameter uncertainty is the surface area of the skin that is exposed to the
product. No studies have been conducted on this value; thus, the assumed surface area of
50 percent of both hands (central estimate) is based on professional judgment. The US EPA
(1996) report assumed that the palms and fingers of both hands would be exposed.
As noted above for the inhalation assessment, there is a high degree of confidence in the
weight fractions and product density for the paint stripper products. There also is a high
degree of confidence in the chosen surface area and body weight values, which are
recommended values in the EFH.
An input value of one was used for exposure duration (day), frequency (events/day), and
averaging time (days). Though these estimates were based on professional judgment, they are
typical for the calculation of acute dermal doses.
Inhalation Exposure. There is a high degree of confidence in the weight fractions and product
density for the paint stripper products. These values are based on currently available consumer
products, as identified in Brown (2012). However, the products were not weighted for percent
of market share. Similarly, there is a high degree of confidence in the values chosen to
represent the house volume and air exchange rate, as they are based on scientifically
defensible data cited in the EFH. The confidence level is similarly high for amount of product
applied and application rates, with data ties to surveys cited in the EFH as well as experiments
conducted in US EPA (1994b). For the stripping sequence, the wait time per segment has a high
level of confidence because the time is based on what is shown on current product labels. The
application and scraping times have a slightly lower confidence level because they are based on
the US EPA (1994b) study, which is considered to be of high quality but only included a limited
number of experiments.
High-quality US EPA (1994b) data were available as a quantitative basis for development of the
estimates for the fraction of applied chemical mass that is released to the indoor air (see the
Estimation of Emission Profiles for Paint Removers/Strippers in Appendix D), but the number of
cases on which the estimates were based was very limited.
The MCCEM inputs for the interzonal airflow rates assumed in the model represent another
area of uncertainty. The chosen rates are tied to an empirical algorithm, by authors whose
report was cited in the EFH. This algorithm is expected to provide a rough approximation of the
average case, but there are numerous consumer choices that can significantly affect the
extent of residential air flow, such as whether to operate a central heating and air conditioning
Page 60

system, if available, and whether to close or open doors to certain rooms or areas in the house.
However, the sensitivity analysis indicated that the modeling results are relatively insensitive to
the value assumed for the interzonal airflow rate.
Given such potential variability across paint stripping exposure scenarios not only for airflow
rates, but also for factors such as amount of product used, application rates, and locations in
the house, uncertainties exist in the percentiles of the distribution that are represented by the
modeled scenarios.
A final/last set of uncertainties is associated with the fit of the exponentially declining emission
rates to the US EPA (1994b) chamber tests, and the extrapolation of the fitted exponentials to
the spray application using the DCM results. Though there are no data for the spray application
of NMP-containing stripper and this is an expedient and reasonable means of filling this data
gap, there is uncertainty in this approach. DCM and NMP have significantly different chemical
properties (e.g., vapor pressure, solubility, melting point, boiling point, etc.). These differences
may result in uncertainties in the extrapolation. For both the brush and spray application, there
are potential chemical equilibrium and rate effects associated with the differences in vapor
pressure and diffusivities. The US EPA (1994b) data were for one specific product on a specific
substrate, and differences between products, additives, and substrates also introduce
uncertainty.
Because of the uncertainties discussed above, the general term upper-end, instead of more
definitive descriptors (e.g., high-end), was used to characterize plausible exposure values
greater than central tendency; more definitive descriptors would imply an inappropriate level
of accuracy.
Regarding the bathtub stripping scenario, it is uncertain whether a DIY consumer would use
practices, based on an occupational scenario, that violate label warnings for ventilation; for this
reason, the user characterization is upper-end to bounding. Given the sensitivity of
concentrations in the ROH to room-of-use ACH and interzonal air flow, there is also uncertainty
about the likelihood that a non-user would be exposed to this scenarios ROH concentrations,
and thus the non-user was characterized as upper-end to bounding. However, under
conditions where the user had protective gear (e.g., independent air supply), it appears more
plausible that the high exposure concentrations could occur in the bathroom, and thus in the
ROH.
3.4.3. Uncertainties in the Hazard- and Dose-Response Assessments
Varying degrees of uncertainty are associated with the evaluation of adverse health effects in
potentially exposed populations to NMP-based paint strippers. Some of the identified sources
of uncertainty in the toxicity assessment follow.
Selection of Developmental Toxicity for the Evaluation of Single Exposure. Developmental
toxicity was used as an endpoint to evaluate risks associated acute and chronic inhalation and
Page 61

dermal exposures to NMP. Though the developmental toxicity studies were to multiple
exposures, they were used to evaluate acute exposure because of the possibility that
developmental effects could manifest after a single exposure to NMP. EPA chose to use a
conservative approach to protect susceptible populations (i.e., women of childbearing age and
pregnant women).
Extrapolation of Dermal PODs Based on Developmental Toxicity to Chronic Occupational
Exposures. The chronic dermal POD was based on a developmental toxicity study that exposed
rats for 10 days (GDs 6 to 15). During pregnancy, women may be exposed to NMP on a
repeated basis, but the exposure does not qualify as a chronic exposure, which is defined in
this analysis as an assumed working lifetime of 40 years. Nevertheless, the repeated nature of
the exposure during pregnancy, specifically if it targets developmental windows of
susceptibility, warranted using developmental toxicity as the most sensitive and conservative
endpoint for the dermal chronic exposures to NMP.
EPA also is interested in the impact of NMP on other subpopulations, such as male workers.
This would require using an alternative dermal POD based on systemic toxicity to assess
potential risks of concern to male workers, instead of using the POD based on developmental
toxicity. Additional chronic dermal toxicity studies might assist the Agency in elucidating other
adverse effects that would not be captured in the developmental toxicity studies. EPA
recognizes that there are uncertainties with current approach which might overestimate the
risks to some worker subpopulations.
Dermal Uptake Duration Inhalation Exposures. Acute or chronic inhalation risks were
evaluated with developmental toxicity studies. The Saillenfait et al. studies (Saillenfait et al.,
2001; Saillenfait et al., 2003; as cited in OECD, 2007) used to select the acute and chronic
inhalation PODs, did not detect NMP aerosols in the inhalation chambers.
Extrapolation of Data Due to Intraspecies Variability. Heterogeneity among humans is
another uncertainty associated with extrapolating the derived PODs to a diverse human
population. The intraspecies UF of 10 was used for all of the derived PODs.
In general, EPA did not have the sufficient data/information on susceptible human populations
or on the distribution of susceptibility in the general population to reduce the default
intraspecies UF of 10 to a lower value (e.g., 1 or 3). As such, EPA used an intraspecies UF of 10
for the risk assessment.
Extrapolation of Data from Animals to Humans. EPA used an interspecies extrapolation UF to
account for uncertainties related to interspecies differences for specific NMP-related
toxicological effects. The standard value for the interspecies UF is 10, which can be broken
down into a factor of ~3 for the adjustment of toxicokinetic differences and a factor of ~3 for
the uncertainty of toxicodynamics.
Page 62

Allometric scaling (BW) was used for the dermal PODs to obtain toxicologically-equivalent
doses across species. The BW correction accounts for toxicokinetic differences supporting an
interspecies UF of 3 for toxicodynamics in the dermal PODs.
This type of scaling is most appropriate for toxicity resulting from the internal dose of the
parent compound integrated over time (i.e., area under the curve or AUC) (US EPA, 2011d),
which EPA assumed for this analysis. Another alternative is that effects are from peak blood
levels. The toxicology experiments on NMP do not provide enough information to distinguish
between a mode of action and which internal dose metric would be most appropriate for these
two modes of action. Narcosis effects are probably due to peak blood levels, and other effects
such as body weight change are more likely from AUC considerations or somewhere between
AUC and peak blood concentration mode(s) of action. The standard EPA approach is to assume
AUC when the mode(s) of action is unknown.
The BW scaling approach has a number of potential limitations that are pertinent to this
analysis and have been described by US EPA (2011d).
Differing allometric patterns among various sized individuals of the same
species (Rhomberg and Lewandowski, 2004, 2006) may pose an uncertainty to
intraspecies scaling, while differences across species in patterns of development
(Finlay and Darlington, 1995; Renwick and Lazarus, 1998; Clancy et al., 2001) can
complicate interspecies extrapolation from immature animals to humans. With
regard to variation in toxicokinetic processes, recent analyses suggest that a
BW3/4 relationship is descriptive of some TK differences observed with
pharmaceuticals among ages including early lifestages, down to about 6 months
(Ginsberg et al., 2004; Ginsberg et al., 2002; Hattis et al., 2004).
Time Scaling for Acute and Chronic PODs. A time extrapolation of acute or chronic PODs was
conducted to obtain PODs that could be used with human exposure estimates calculated in the
exposure assessment. Time scaling assumed that the effects are related to concentration
time, independent of the daily (or weekly) exposure regimen (i.e., a daily exposure of six hours
to four mg/m3 is considered equivalent to 24 hours of exposure to one mg/m3). However, the
validity of this assumption is unknown.
Page 63
3.5. RISK ASSESSMENT CONCLUSIONS

NMP is used in the home and commercially as a paint stripper. Exposures may occur by the
dermal and inhalation routes. Consumer acute dermal and inhalation exposures were modeled
to develop TWAs for a number of durations up to 24 hours for a number of scenarios. For
worker exposures, acute and chronic dermal exposures were modeled. Chronic inhalation
exposures were developed from a limited number of published monitoring studies.
Developmental toxicity studies were used to develop the acute and chronic dermal and
inhalation PODs. These values were converted to human equivalent doses or concentrations.
The MOEs were compared to a benchmark level of 30. This value accounted for intra- and
interspecies uncertainty. MOEs below 30 were interpreted as potential risks of concern.
Occupational MOEs for dermal chronic exposures ranged from 2.5 to 7.6. These values were
below the benchmark level of 30 and indicated potential risks of concern. Occupational MOEs
for inhalation chronic exposures ranged from 75 to 10,857 with the BMCL HEC approach. These
values exceeded the benchmark level of 30 and indicated negligible risks of concern. However,
the EPA considers these MOEs unreliable because of the limited amount of inhalation exposure
data. Consumer MOEs ranged from 0.51 to 1.1 for acute dermal exposures. Consumer MOEs
for acute inhalation exposures ranged from 0.87 to 98 using the BMCL HEC approach.
Based on these MOEs and the previously stated uncertainties, EPA has made the following
conclusions, which are limited to women of child-bearing age:
Workers may have potential risks of concern from dermal exposure when no gloves are
worn.
Consumers may have potential risks of concern from dermal exposure assuming
appropriate gloves are not worn.
Consumers may have potential risks of concern from inhalation exposure (although of lower
concern than from dermal exposure) if exposed for more than 4 hours at lower ventilation
rates.
Page 64
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Page 76
Appendices
Page 77
Appendix A. Environmental Effects Summary

EPA evaluated available published studies to better understand the potential environmental
effects of NMP releases to the environment on aquatic organisms including (i.e., acute and
chronic toxicity) invertebrates, fish, and plants, as well as to birds. A summary of these data is
provided in Table A-1.
Table A-1. Summary Table for Aquatic Toxicity Data of NMP
Endpoint
Fish 96-hour LC 50 (mg/L)
Aquatic invertebrate 48-hour EC 50 (mg/L)
Value
>500-4,030
>1,000-4,897
Aquatic plant 72-hour EC 50 (mg/L)
>500
Aquatic invertebrate chronic toxicity 21-day (mg/L)
12.5
Avian toxicity LD 50 (mg/kg body weight)

Avian toxicity LC 50 (ppm)
2,500-5,000
>5,000
Environmental Effects Aquatic Toxicity

The aquatic toxicity of NMP fish, aquatic invertebrates, and aquatic plants is low. The toxicity
of NMP for avians is low (US EPA, 1992b, 2012c). The acute 96-hour LC 50 for fish ranges from
>500 to 4,030 mg/L. The acute 48- and 96-hour EC 50 for aquatic invertebrates ranges from
>1,000 to 4,897 mg/L. The toxicity for aquatic plants is >500 mg/L. The chronic toxicity for
aquatic invertebrates is 12.5 mg/L. A brief summary of the environmental toxicity is described
below.
Acute Toxicity to Fish
Fathead minnows (Pimephales promelas) were exposed to unspecified measured
concentrations of NMP under flow-through conditions for 96 hours. A 96-hour LC 50 of
1,072 mg/L was reported (SRC, 1979; as cited in Verschuren, 2009).
Orfe (Leuciscus idus) were exposed to unspecified concentrations of NMP for 96 hours. No
other details about the study was provided. A 96-hour LC 50 of 4,000 mg/L was reported (BASF
AG, 1986; as cited in Verschuren, 2009).
Guppies (Poecilia reticulata) were exposed to unspecified nominal concentrations of NMP
under static conditions for 96 hours. A 96-hour LC 50 of 2,673 mg/L was reported (Weisbrod and
Seyring, 1980; as cited in OECD, 2007; and Verschuren, 2009).
Bluegill sunfish (Lepomis macrochirus 10/replicate) were exposed to nominal concentrations of
0, 360, 600, 1,00, 1,667, 2,775, and 4,629 mg/L of NMP under unspecified conditions for
96 hours. A 96-hour LC 50 of 832 mg/L was reported (GAF Corp., 1979; as cited in OECD, 2007;
and Verschuren, 2009).
Page 78

Rainbow trout (Oncorhynchus mykiss, formerly known as Salmo gairdneri, 10/replicate) were
exposed to a single concentration of NMP of 500 mg/L under static conditions for 96 hours. A
96-hour LC 50 of >500 mg/L was reported (SRC, 1979; BASF AG, 1983; as cited in OECD, 2007).
Acute Toxicity to Aquatic Invertebrates
Water fleas (Daphnia magna) were exposed to unspecified nominal concentrations of NMP
under static conditions for 48 hours. A 48-hour EC 50 of 4,897 mg/L was reported (GAF Corp.,
1979; as cited in OECD, 2007; and Verschuren, 2009).
Water fleas (D. magna) were exposed to unspecified concentrations of NMP under unspecified
conditions for 48 hours. A 48-hour EC 50 of 1,230 mg/L was reported (Lan et al., 2004).
Grass shrimp (Palaemonetes vulgaris) were exposed to unspecified nominal concentrations of
NMP under static conditions for 48 hours. A 96-hour EC 50 of 1,107 mg/L was reported (GAF
Corp., 1979; as cited in OECD, 2007; and Verschuren, 2009).
Chronic Toxicity to Aquatic Invertebrates
Water fleas (D. magna) were exposed to unspecified concentrations of NMP under unspecified
conditions for 21 days. A two-day NOEC of 12.5 mg/L was reported (BASF AG, 2001; as cited in
OECD, 2007).
Toxicity to Aquatic Plants
Green algae (Scenedesmus subspicatus) were exposed to unspecified nominal concentrations of
NMP under static conditions for 96 hours. A 72-hour EC 50 of >500 mg/L was reported (BASF
AG, 1988b; as cited in Verschuren, 2009).
Toxicity to Avians
Bobwhite quails (Colinus virginianus) (five male and five female) were orally dosed at
concentrations of 0, 312.5, 625, 1,250, 2,500, and 5,000 mg/kg body weight of NMP for 14 days.
The LD 50 values ranged between 2,500 and 5,000 mg/kg body weight (Hazelton Laboratories
America, 1980; as cited in OECD, 2007).
Mallard ducks (Anas platyrhynchus) were exposed (through basal feed) to concentrations of 0,
156.3, 312.5, 625, 1,250, 2,500, and 5,000 ppm of NMP for eight days. No mortalities were
observed and an LC 50 of >5,000 ppm was derived from this study (Hazelton Laboratories
America, 1979; as cited in OECD, 2007).
Page 79
Appendix B. Biomonitoring Data

The following paragraphs were extracted from the OECD document (OECD, 2007).
Exposure to NMP can be evaluated by combining standard toxicokinetic
methodologies with measurements of the level of 5HNMP, the principal
metabolite of NMP, in plasma or urine. There is also a very good correlation
between NMP exposure and the metabolites MSI and 2HMSI (Akesson and
Paulsson, 1997; Jonsson and Akesson, 2003; Akesson and Jonsson, 2000; Jonsson
and Akesson, 2001; Anundi et al., 2000).
Within the frame work of an occupational field study, individual exposures to
NMP were investigated in 7 workers and 3 scientific co-workers, who used a
cleaner containing NMP to remove resin from mixing drums and tools. The
average NMP concentration in the ambient air was about 3 mg/m in the mixing
area with short-term peak concentrations of up to 19 mg/m in the vicinity of the
cleaning activity. The parent compound NMP and metabolite 5HNMP were
found in the post shift urine samples. None of the exposed workers reported
symptoms such as respiratory irritation or headache. Air measurements and
biomonitoring results were comparable to those reported by other working
groups (Akesson and Jonsson, 2000; Anundi et al., 2000). Furthermore, it was
demonstrated that dermal absorption accounts for the majority of the internal
NMP burden (Bader et al., 2003; Wrbitzky and Bader, 2003).
A representative end user exposure to NMP was investigated in 4 male
volunteers during paint stripping of furniture using a commercial product
containing NMP (19 percent), limonene (<1 percent), and dibasic ester (75
percent). The air concentrations of NMP during the 2 to 3 hour exposure period
averaged 0.4 to 3.8 mg/m. As an indication of dermal and inhalation uptake,
the maximum urinary levels of NMP and 5HNMP were 0.11 mg NMP/l and 7.4
mg 5HNMP/l, respectively. Valid values for 2HMSI could not be obtained (Will et
al., 2004).
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Appendix C. Occupational Exposure Assessment Support

Information
This appendix contains the following information:
Derivation of NMP Concentration Conversion Factor for Occupational Exposure

Calculations
Paint Stripping Processes and Associated Worker Activities
Facility and Population Data and Information
Occupational Exposure Literature Data
Dermal Exposure Modeling
DERIVATION OF NMP CONCENTRATION CONVERSION FACTOR FOR OCCUPATIONAL

EXPOSURE CALCULATIONS
A factor to convert between airborne concentrations measured in volume- or mole-based ppm
and airborne concentrations measured in mg/m3 was not identified in the literature search.
Therefore, a conversion factor was derived and the methodology of this derivation is presented
here.
To convert the units of concentration between a volume- or mole-based ppm to mg/m3 at
ambient room conditions, it is assumed that the ideal gas law applies to a mixture of NMP and
air at ambient conditions. The mass-based concentration of NMP in air from the ideal gas law is
solved for as follows:
(C-1)
where:
C
m
V
y
P
M
R
T
=
=
=
=
=
=
=
=
NMP concentration (mg/m3);

total mass of NMP (mg);
total volume of gas (m3);
mole fraction of NMP (mol/mol);
total pressure (atm);
molecular weight of NMP (g/mol);
universal gas constant (m3-atm/kmol-K); and
temperature (K).
Here, the mole fraction of NMP, y, is equal to the NMP concentration in ppm divided by one
million. At ambient conditions (one atm and 298 K), with an NMP molecular weight of 99.13
Page 81

g/mol and a gas constant of 0.082 m3-atm/kmol-K, the unit conversion is 4.06 mg/m3 per ppm
of NMP.
DESCRIPTIONS OF OCCUPATIONAL PROCESSES AND ACTIVITIES

Techniques for paint stripping typically include manual coating, tank dipping, and spray
application (TNO, 1999). Pouring, wiping, and rolling are also possible application techniques,
and application can be manual or automated (ECHA, 2011). An individuals exposure to paint
stripping chemicals greatly depends on control measures taken and work practices adopted
(TNO, 1999). The following sections summarize processes and activities for the industries found
to employ paint stripping.
Paint Stripping By Professional Contractors
Paint strippers can be used by professional contractors to strip paint and varnish from walls,
wood flooring, and kitchen and wood cabinets. Professional contractors are expected to
purchase strippers in commercially available container sizes that commonly range from one
liter up to five gallons, although they may also purchase consumer paint stripper products from
hardware stores. Stripper is typically applied to wall or floor surfaces using a hand-held brush.
Strippers used in these applications often have a high viscosity since they can be applied to
vertical surfaces. After application, the stripper is allowed to set and soften the old coating.
Once the stripper has finished setting, the old coating is removed from the surface by scraping
and brushing. During wood floor stripping, old coating and stripper may also be removed using
an electric floor buffer. After the old coating is removed, the surface is wiped clean before
moving to the next stages of the job. The stripping process is often completed on an
incremental basis with treatment for one section of wall or flooring being completed before
moving to the next section (EU, 2007; IRTA, 2006; NIOSH, 1993; TNO, 1999).
Paint Stripping at Automotive Body Repair and Maintenance Shops
Automotive refinishing shops apply coatings to motor vehicles subsequent to the original
manufacturing process. The overall refinishing process typically involves the following steps:
Structural repair;
Surface preparation (cleaning and sanding);
Primer coat mixing;
Spray application of primer coat;
Curing;
Sanding;
Solvent wipe-down;
Topcoat (basecoat color and clearcoat) mixing;
Spray application of topcoat; and
Curing.
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The surface preparation step of the refinishing process involves removing residual wax, grease,
or other contaminants from the surface to be painted, to ensure adhesion of the new coating.
The new coating may be applied over an existing coating if it is free of chips or cracks after it
has been roughened through sanding. Alternatively, the previous coating may be removed
using a mechanical method (e.g., sanding) or a paint-removing solvent. After the coating is
roughened or removed, the surface is typically wiped down with a solvent- or water-based
surface preparation product (OECD, 2010). More detailed information on the methods used to
apply paint stripper to motor vehicles was not identified.
Wood Furniture Stripping
During furniture stripping, paint stripper may be applied to the furniture by either dipping the
furniture in an open tank containing the stripper, brushing or spraying the stripper onto the
furniture surface, or manually applying the stripper. Larger facilities may pump the stripper
through a brush. The application method depends on the size and structure of the furniture as
well as the capabilities of the facility. The application area typically has a sloped surface to
allow for collection and recycling of unused stripper. Larger facilities use a flow tray to apply
the stripper to parts. The flow tray is a sloped, shallow tank with a drain at the lower end.
After application, the stripper is left to soak on the furniture surface to soften the surface
coating. Once soaking is complete, the unwanted coating is scraped and brushed from the
furniture surface. The furniture is then transferred to a washing area where residuals are
washed from the furniture. Washing can be performed using low-pressure washing operations
or high-pressure water jets or high-pressure wands. Wash water may contain oxalic acid to
brighten the wood surface. Wash water is collected and either recycled or disposed of as
waste. After washing, the furniture is transferred to a drying area where it is allowed to dry
before being transferred to other refinishing processes (e.g., sanding, painting, reupholstery)
(IRTA, 2006; HSE, 2001; NIOSH, 1990, 1992).
Larger facilities likely purchase stripper in drum quantities from suppliers. Smaller facilities that
use hand stripping instead of stripping equipment likely purchase their stripper from hardware
and home improvement stores. Stripper applied using application equipment has low viscosity
so it can be pumped through the pumps in the flow tray. Stripper applied using hand stripping
are typically more viscous so they will remain on the part long enough to strip the coating
(IRTA, 2006).
Figure C-1 shows a typical flow tray used by larger furniture strippers to apply stripper to
furniture parts, obtained from IRTA (2006). Figure C-2 shows a typical water wash booth used
to wash stripper and coating residue from stripped furniture, obtained from IRTA (2006).
Figure C-3 shows an example diagram of a dipping tank for furniture stripping complete with
local exhaust ventilation, obtained from HSE (2001).
Page 83
Figure C-1. Typical Flow Tray for Applying Stripper to Furniture (IRTA, 2006).
Figure C-2. Typical Water Wash Booth Used to Wash Stripper and Coating Residue from Furniture
(IRTA, 2006).
Page 84
Figure C-3. Example Diagram of a Dipping Tank for Furniture Stripping (HSE, 2001).
Art Restoration and Conservation

Art restoration and conservation can include the care and maintenance of paintings to reverse
negative effects of aging and dirt accumulation. It can also include repairing paintings that have
suffered paint loss, weakened canvas, tears, water damage, fire damage, and insect damage
(Smithsonian, 2012a). Art restoration and conservation can include paint cleaning, which can
entail removing dirt and other obscuring material, removing varnish, or removing overpaint
while maintaining the original layer of paint (Smithsonian, 2012b). These activities can involve
the use of paint strippers. Although paint strippers used in this field can contain DCM, the use
of DCM is not always favored as DCM can penetrate through the overpaint layer that is being
removed and into the original paint layer that is being conserved. NMP may serve as a suitable
alternate for DCM in strippers used in this field (Wollbrinck, 1993). More detailed information
on the use of paint strippers in art restoration and conservation was not identified. It is
anticipated that paint strippers are applied manually in this field.
Aircraft Paint Stripping
During aircraft paint stripping, paint stripper is pumped from bulk storage containers and
applied to the body of the aircraft using hoses. Once the paint stripper has been applied, it is
allowed to set for a certain period of time (usually about 30 minutes) to allow the paint to
soften. Once setting is complete, the stripper and loose paint are scraped down into a
collection area. Any remaining stripper and paint residue are then brushed away with water
Page 85

and brushes. Once the surface of the aircraft has dried, a new layer of primer, paint, and top
coat are applied (NIOSH, 1977).
Ship Paint Stripping
Process description information for paint stripping of ships has not been identified. It is
anticipated that paint stripping of ships may involve similar processes as the paint stripping of
aircraft.
FACILITY AND POPULATION DATA

This section summarizes data on the number of establishments, number of paid employees and
workers, and production hours and work day estimates (for manufacturing industries). It may
be noted that population demographics were not examined for this assessment, but may be
worthy of consideration in a more detailed assessment. For example, some segment of the
worker population could include children (e.g., teenagers).
Paint Stripping By Professional Contractors
Table C-1 summarizes the number of establishments and average number of construction
workers for painting and wall covering contractors and flooring contractors according to the
2007 US Economic Census. The Census data do not include hours worked for construction
industry sectors. Note that these Census data do not include bathtub refinishers/reglazers.
Census data that include bathtub refinishers/reglazers were not identified.
Table C-1. 2007 US Economic Census Data for Painting and Wall Covering and Flooring Contractors.
2007 Number of
Establishments
2007 Average Number of

Construction Workers
Painting and Wall

Covering Contractors
35,619
174,276
Flooring Contractors
14,575
49,085
2007 NAICS
2007 NAICS Title
238320
238330
Source: US Census (2007a).
The number of painting and wall covering contractors and flooring contractors who use NMPbased paint strippers, or the number of jobs per yr a contractor uses NMP-based paint
strippers, and the exact number of construction workers within a job site exposed to NMPbased paint strippers are unknown. Therefore, the number of establishments and construction
workers from the US Census are possibly overestimates of the number of establishments and
construction workers potentially exposed to NMP during paint stripping.
Table C-2 summarizes the number of establishments and average number of paid employees
for automotive body, paint, and interior repair and maintenance according to the 2007 US
Economic Census. The Census data do not include hours worked for this industry sector.
Page 86
Table C-2. 2007 US Economic Census Data for Automotive Body, Paint, and Interior Repair and
Maintenance.
2007 NAICS
2007 NAICS Title
811121
Automotive Body, Paint,

and Interior Repair and
Maintenance
2007 Number of
Establishments
2007 Number of Paid

Employees
35,581
223,942
The present day number of automotive body repair and maintenance shops within the US that
use NMP-based paint strippers, and the number of employees within an establishment exposed
to NMP-based paint strippers are unknown. Therefore, the number of establishments and
employees from the US Census are possibly overestimates of the number of establishments and
employees potentially exposed to NMP during paint stripping.
for reupholstery and furniture repair according to the 2007 US Economic Census. The Census
data do not include hours worked for this industry sector.
Table C-3. 2007 US Economic Census Data for Reupholstery and Furniture Repair.
2007 NAICS
2007 NAICS Title
811420
Reupholstery and Furniture

Repair
2007 Number of
Establishments
2007 Number of Paid

Employees
4,693
16,142
The present-day number of reupholstery and furniture repair establishments that use NMPbased paint strippers and the number of employees within an establishment exposed to NMPbased paint strippers are unknown. Therefore, the number of establishments and employees
from the US Census are possibly overestimates of the number of establishments and employees
potentially exposed to NMP during paint stripping.
for independent artists, writers, and performers and museums according to the 2007 US
Economic Census. The Census data do not include hours worked for these industry sectors.
Page 87
Table C-4. 2007 US Economic Census Data for Industry Sectors that May Engage in Art Restoration and
Conservation Activities.
2007 Number of
Establishments
2007 Number of Paid

Employees
Independent Artists,
Writers, and Performers
20,612
48,321
Museums
4,664
83,899
2007 NAICS
2007 NAICS Title
711510
712110
NAICS code 711510 includes a wide variety of professions, including independent art restorers
and independent conservators. The majority of the professions listed within this NAICS code
according to the US Census Bureau are not expected to engage in paint stripping. Furthermore,
the extent that art restorers and conservators engage in paint stripping, particularly using NMPbased paint strippers, is unknown. Similarly, the number of museums within NAICS code
712110 that engage in paint stripping, and use NMP-based paint strippers, is unknown.
Therefore, the number of establishments and employees from the US Census are likely
overestimates of the number of establishments and employees potentially exposed to NMP
during paint stripping.
Table C-5 summarizes the number of establishments, average number of production workers,
and production workers hours for aircraft manufacturing according to the 2007 US Economic
Census. The table also estimates the average worker days per yr and average worker hours per
day. These parameters are estimated from the production workers hours and the average
number of production workers. The average worker days per yr are estimated assuming eight
worker hrs/day, and the average worker hours per day are estimated assuming 250 worker
days/yr. The estimates of worker days per yr and worker hours per day are within 10 percent
of the EPA New Chemicals Program default values of 250 days/yr and eight hrs/day,
respectively.
Table C-5. 2007 US Economic Census Data for Aircraft Manufacturing.
Parameters Calculated from the
Corresponding 2007 Economic
Census Data
2007 Economic Census Data
2007
NAICS
Code
2007 NAICS
Title
336411 Aircraft
Manufacturing
Average
Average
Production Average Worker
Worker Hours
Number of
Workers
Number of
Days per Yr
per Day
Establishments Production Hours (1,000
(Assuming
(Assuming 250
Workers
8 hrs/day)
Hrs)
Days/yr)
254
81,456
157,589
242
7.74
Page 88
The present-day number of aircraft manufacturing establishments that use NMP-based paint
strippers and the number of employees within an establishment exposed to NMP-based paint
strippers are unknown. Therefore, the number of establishments and employees from the US
Census are possibly overestimates of the number of establishments and employees potentially
exposed to NMP during paint stripping.
Table C-6 summarizes the number of establishments, average number of production workers,
and production workers hours for ship building and repairing according to the 2007 US
Economic Census. The table also estimates the average worker days per yr and average worker
hours per day. These parameters are estimated from the production workers hours and the
average number of production workers. The average worker days per year are estimated
assuming eight worker hrs/day, and the average worker hours per day are estimated assuming
250 worker days/yr. The estimates of worker days per yr and worker hours per day are within
10 percent of the EPA New Chemicals Program default values of 250 days/yr and eight hrs/day,
respectively.
Table C-6. 2007 US Economic Census Data for Ship Building and Repairing.
Parameters Calculated from
the Corresponding 2007
Economic Census Data
2007 Economic Census Data
2007
NAICS
Code
2007 NAICS
Title
336611 Ship building

and repairing
Number of
Establishments
656
Average
Average
Average
Production
Worker Days Worker Hours
Number of
Workers
per Yr
per Day
Production Hours (1,000
(Assuming
(Assuming
Workers
Hs)
8 Hours/day) 250 Days/yr)
65,737
136,929
260
8.33
The number of ship building and repair establishments that use NMP-based paint strippers and
the number of employees within an establishment exposed to NMP-based paint strippers are
unknown. Therefore, the number of establishments and employees from the US Census are
possibly overestimates of the number of establishments and employees potentially exposed to
NMP during paint stripping.
Respiratory Protection
The 13 MSDSs for paint strippers obtained through the literature search were reviewed for
recommended respiratory protection information. Of these 13 MSDSs, only three contained
NMP, one of which also contained DCM. One of the NMP-only MSDSs recommends a NIOSHapproved respirator for organic solvent vapors without further specification of the respirator
type (WM Barr, 2011). The second NMP-only MSDS recommends that a NIOSH/MSHA-
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approved air-purifying respirator with an organic vapor cartridge or canister may be permissible
under certain circumstances where airborne concentrations are expected to exceed exposure
limits (WM Barr, 2009a). It further states that protection provided by air-purifying respirators
may be limited, in which case, a positive pressure, air-supplied respirator is recommended
(such as for uncontrolled releases or unknown exposure levels) (WM Barr, 2009a). The MSDS
for the paint stripper that contained both DCM and NMP recommends a NIOSH-approved selfcontained breathing apparatus (SCBA) (WM Barr, 2009b). However, the recommendation for
SCBA is likely heavily influenced by the presence of DCM in addition to NMP.
Dermal Protection
The 13 MSDSs for paint strippers obtained through the literature search were reviewed for
recommended dermal protection information. Of these 13 MSDSs, only three contained NMP,
one of which also contained DCM. All of the three MSDSs recommend either chemical-resistant
or impermeable gloves. One MSDS recommended nitrile gloves and another recommended
nitrile or neoprene gloves. All of the three MSDSs recommend safety glasses, chemical goggles,
or face shields for eye protection or where eye or face contact is likely (WM Barr, 2009b, a,
2011).
OCCUPATIONAL INHALATION EXPOSURE LITERATURE DATA

This assessment uses existing exposure data to estimate occupational exposures to NMP by
inhalation. Several exposure studies were identified through a literature search.
Paint Stripping by Professional Contractors
In 1993, NIOSH was requested to conduct a health hazard evaluation (HHE) during the
renovation of an antique residence in Atlanta, Georgia. NIOSH was requested to conduct the
HHE by the owner of a wood flooring and restoration company for the purpose of assessing
exposures during the use of an experimental solvent to remove paint from the wood floor of
the building. The solvent was highly viscous, had a pH of two to three and a vapor pressure of
five to six mmHg at 20 oC, and its primary component was NMP (at 65 to 79 percent). The
renovation work was conducted entirely by the company owner. NIOSH conducted air
sampling on November 27 and December 14, 1993 and obtained personal breathing zone and
area air samples (NIOSH, 1993).
The worker paint stripped the floor using a passive refinishing method. In this method, the
worker brush-applies the solvent to the floor, allows it to set for 30 to 60 minutes, then uses a
powered electric buffer with bristles to agitate and dislodge the loosened paint. The worker
then uses a rubber squeegee to remove the spent solvent-paint mixture and mixes it with
sawdust for disposal. Sawdust is applied to the floor, scrubbed with a wire brush, and scraped
with a putty knife. The worker applies a water-alcohol mixture and additional sawdust to the
floor, performs additional buffing with an abrasive disc, and repeats the process if needed
(NIOSH, 1993).
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On the November 22nd sampling day, the average concentration of the personal, breathing zone
samples was 3.3 ppm (13.4 mg/m3) (sampling times ranged from 46 to 93 minutes). Area
samples taken at two feet and five feet above the floor had average concentrations of 3.9 ppm
(15.8 mg/m3) and 3.6 ppm (14.6 mg/m3), respectively (sampling times ranged from 40 to
127 minutes). The door to the room was kept closed for the duration of the work, but the
window was both closed and opened during the work day. The lowest concentrations were
observed while the window was open and while solvent was not being applied to the floor
(NIOSH, 1993).
On the December 14th sampling day, the average concentration of the personal, breathing zone
samples was 4.0 ppm (16.2 mg/m3) (sampling times ranged from 43 to 52 minutes). Area
samples taken two feet above the floor had an average concentration of 7.7 ppm (31.2 mg/m3)
(sampling times ranged from 42 to 46 minutes). The door to the room was again kept closed
for the duration of the work, but the window was also kept closed the entire work day due to
inclement weather. The higher concentrations were expected due to the closed window as
compared to the first sampling day (NIOSH, 1993).
NIOSH noted that the worker wore a half-mask air-purifying respirator with organic vapor
cartridges during the paint stripping process. NIOSH further noted that protective gloves were
used intermittently and no mechanical ventilation was used during the renovation (NIOSH,
1993).
An EU report states that there is probablyno fundamental difference between the
application of paint removers by professional painters and consumers and goes on to further
state that, in regard to the cited consumer exposure studies, the test situations and data
describedare assumed valid for occupational exposure during professional use as well (TNO,
1999). However, professional contractors are expected to have a higher frequency of exposure
as compared to consumers. It is also not clear whether overall activity patterns and practices of
contractors match those of consumers or whether the overall distributions of exposures of
contractors and consumers have any semblance to one another. Despite these uncertainties,
some of the literature data for consumers may be considered.
Midwest Research Institute (MRI) prepared a report for EPA in 1994 that resulted from an
experimental investigation of consumer exposures to solvents contained in paint stripping
products with eliminated or reduced DCM content. MRI investigated five paint strippers, two
of which contained DCM (along with other solvents, but the concentrations were not specified).
The paint stripping was conducted in a laboratory-based, environment-controlled, room-sized
test chamber. The paint strippers were used on a plywood panel coated with a primer coat and
two finish coats. The air exchange rate for the experiments ranged from 0.54 to 0.76 ACH, with
an average of 0.58 ACH. The air exchange rate of approximately 0.5 ACH was intended to
replicate the ventilation rate of an enclosed room in a typical residence as a worst-case
scenario. During each experiment, the following samples were taken: a personal breathing
zone sample of the test subject using the paint stripper; two stationary air samples for the
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duration of the paint stripping task; and one stationary air sample beginning at the start of the
paint stripping and lasting for eight hours (US EPA, 1994b).
In the MRI investigation, the only NMP-based paint stripper was brush applied. The breathing
zone concentrations of NMP ranged from 37 to 39 mg/m3 (9.1 to 9.6 ppm). The stationary
length-of-task concentrations ranged from 38 to 45 mg/m3 (9.4 to 11.1 ppm). The eight-hour
TWA concentrations ranged from 46 to 74 mg/m3 (11.3 to 18.2 ppm) (US EPA, 1994b).
NMP exposure data from paint stripping during automotive body repair and maintenance were
not identified.
NMP exposure data from paint stripping of wood furniture were not identified.
NMP exposure data associated with art restoration and conservation were not identified.
NMP exposure data from paint stripping of aircraft were not identified.
NMP exposure data from paint stripping of ships were not identified.
Paint Stripping in Graffiti Removal and other Non-specific Workplace Settings
Some NMP exposure data were identified for which work place settings were not specified and
more specific information on the industries (such as applicable NAICS or Standard Industrial
Classification [SIC] codes, primary industrial functions or products, or number of sites or
workers) were not provided in the identified reference.
A 2001 report by the World Health Organization (WHO) identified NMP exposures from graffiti
removers in the literature. Personal breathing zone concentrations were as high as 10 mg/m3
(2.5 ppm) for both peak exposure and eight-hour TWA exposure (WHO, 2001). A literature
search conducted by the NMP Producers Group identified four studies of graffiti removing
(ranging from 1993 to 2004), which resulted in short-term exposures ranging from 0.01 to
30 mg/m3 (0.002 to 7.4 ppm), and eight-hour TWA exposures ranging from 0.03 to 4.52 mg/m3
(0.007 to 1.1 ppm) (NMP Producer's Group, 2012).
The same WHO report also identified NMP exposures in a non-specified paint stripping industry
in the literature. Personal breathing zone samples had eight-hour TWA exposures as high as
64 mg/m3 (16 ppm) and one-hour peak exposures as high as 280 mg/m3 (69 ppm) (WHO, 2001).
The NMP Producers Group literature search results were in general agreement with the WHO
report. The NMP Producer Group identified four studies of non-specified paint stripping
activities with peak exposure as high as 280 mg/m3 (69 ppm) (the same study cited in the WHO
Page 92

report). Additional exposures from additional studies were identified as low as 0.01 mg/m3
(0.002 ppm), but the sampling time was not specified (NMP Producer's Group, 2012).
DERMAL EXPOSURE MODELING

Dermal exposure modeling was employed to estimate dermal exposures to NMP in liquid
products. A summary of relevant data from the literature search and the modeling information
follows. Direct exposures to children (e.g., teenagers) who may use these products in work,
training, or other situations are not expected to differ significantly from that of adults;
therefore, their exposures would likewise not be expected to differ significantly.
Dermal exposure data of NMP specifically as related to paint stripping were not identified
during the literature search. Some permeability information was found. A 1995 experimental
investigation measured the permeability of various solvents through living human skin. The
permeability rate of NMP was measured to be 171 g/m2-hour (Ursin et al., 1995). Also, a
European report on NMP calculated dermal exposure dose to NMP assuming a maximum
absorption through the skin of 100 percent (SCCS, 2011).
This assessment estimates dermal exposures to liquid products containing NMP using EPA
models. EPA has developed a series of standard models for quantitatively estimating worker
dermal exposures to liquid and solid chemicals during various types of activities; this series of
models cannot be used for dermal exposures to vapors. To estimate dermal exposure, all of
these dermal exposure models assume that a specific surface area of the skin is contacted by a
material containing the chemical of interest, as well as a specific surface density of the material
on the skin (quantity of the liquid or solid material containing the chemical that remains on the
skin after contact, in mg/cm2-event). The models also assume no use of controls or gloves to
reduce the exposure. These assumptions and default parameters are defined based on the
nature of the exposure (e.g., one hand or two hand, immersion in material, contact with
surfaces). The standard EPA dermal model equation is shown in Equation C-2 (US EPA, 1991a,
2000).
(C-2)
where:
EXP dermal
AREA surface =
Q remain_skin =
dermal exposure, as a potential dose rate, to the liquid or solid chemical per
day (mg chemical/worker-day);
surface area of the skin that is in contact with liquid or solid material
containing the chemical (840 cm2; EPA/OPPT 2-Hand Dermal Contact with
Liquid Model);
quantity of the liquid or solid material containing the chemical that remains
on the skin after contact (0.7 to 2.1 mg/cm2-event; EPA/OPPT 2-Hand Dermal
Contact with Liquid Model);
Page 93

F chem
N event
weight fraction of the chemical of interest in the material being handled in

the activity (assume 1; i.e., up to 100 percent NMP); and
frequency of events for the activity (EPA default = one event/worker-day).
Dermal dose rates in this report are estimated in units further normalized by worker body
weight, as indicated in Equation C-3:
(C-3)
where:
EXP dermal_bw =
EXP dermal
BW worker
dermal exposure, as a potential dose rate, to the liquid or solid chemical per
day normalized by worker body weight (mg chemical/kg-day);
dermal exposure to the liquid or solid chemical per day (mg
chemical/worker-day); and
body weight of an average worker (kg; EPA default value = 80 kg (US EPA,
2011c).
It is important to note that this EPA dermal exposure model uses a default value of one
exposure event per worker per day. However, highly volatile or high skin absorption chemicals
can cause variations of surface densities, which can also be impacted by the number of
exposure events per worker per day. If a chemical with high skin absorption, such as NMP,
absorbs into the workers skin during the workers shift, the workers additional exposure
events of NMP during the shift can serve to replenish the surface density. Therefore, the EPA
default value of one exposure event per worker per day may not be appropriate for NMP;
however, a more appropriate value has not been determined.
Dermal exposures to NMP liquid are estimated using the EPA/OPPT 2-Hand Dermal Contact
with Liquid Model and the default values provided above. Assuming a stripper content of
100 weight percent NMP, the following values are estimated: dermal exposure to liquid
(EXP dermal ) of 590 to 1,800 mg NMP/day as potential dose rates, and dermal exposure
normalized by body weight (EXP dermal_bw ) of 7.4 to 22 mg NMP/kg-day as acute potential dose
rates. Also, assuming a maximum absorption through the skin of 100 percent (SCCS, 2011),
absorbed dose rates may be assumed to be equal to potential dose rates.
Page 94
Appendix D. Consumer Exposure Assessment

ESTIMATION OF EMISSION PROFILES FOR PAINT REMOVERS/STRIPPERS
In 1993, MRI conducted a series of chamber studies for EPA on five paint stripping products,
including two containing DCM and one containing NMP, as shown in Table D-1 (US EPA, 1994b).
For each study, continuous air concentrations were measured using a Fourier transform
infrared (FTIR) spectrometer. In addition, three stationary samplers and a personal sampler
were used to collect an integrated sample on activated charcoal. These data were analyzed and
a process was undertaken to fit the data to exponential equations to represent the time-varying
emission profile that led to the air concentrations.
Table D-1. MRI Studies: Products Emissions Fit to Exponential Profile.
Product
Application Type
Chemical
BIX Spray-On Stripper
Spray
DCM
Strypeeze
Brush
DCM
Wood Finishers Pride
Brush
NMP
In evaluating the experimental data, an exponential emission was chosen because of the
general shape of the concentration profile and similarity to other emission behavior (e.g.,
chemicals from paint). The emission equation has the following form:
(D-1)
where:
E 0 = initial emission rate (the emission rate at t = 0), mg/hour
k = first-order rate constant, hour-1
t = time since application, hour
Integrating Equation C-1 to time of infinity gives the mass released represented by the
exponential, as follows:
Mass Released
(D-2)
E 0 = (Mass Released) * k
(D-3)
or:
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Integration of the single compartment, mass-balance equation for the air concentration
equation for a single and double exponential representation of the emissions is given in
Equations D-4 and D-5 (US EPA, 1997), respectively.
(D-4)
where:
V = chamber volume, m3
Q = air flow rate in and out of the chamber, m3/hour
(D-5)
where:
E 01 = initial emission rate for the first exponential, mg/hour
E 02 = initial emission rate for the second exponential, mg/hour
k 1 = first-order rate constant for the first exponential, hour-1
k 2 = first-order rate constant for the second exponential, hour-1
The two DCM products were applied in eight, approximately one-minute applications, with
each one-minute application followed by an approximately 10-minute wait time prior to the
start of the subsequent application, resulting in about 11 minutes between applications. In
each case, the emissions from each application are represented by a single or double
exponential, with each exponential identical to the other seven, but with a different start time
set at the midpoint of the application period. Based on this approach, the start times of the
eight DCM exponentials are 0.5, 11.5, 22.5, 33.5, 44.5, 55.5, 66.5, and 77.5 minutes from the
start of the stripping activity, respectively.
For the two DCM products, a single exponential was found to provide a good fit to the data.
The fitting process involves:
(1) Extracting measured concentration values from the US EPA (1994b) data and co-plotting
the points with Equation D-4. The concentration values were extracted for runs 4, 5,
and 6 for BIX Spray-On and runs 7, 8, and 9 at each 0.5-hour time point as well as peaks
and significant changes in slope. This resulted in eight or nine data points per run.
(2) Calculating the mass of DCM applied during the test and assigning 1/8th of the applied
mass to each of the eight exponentials.
(3) Iterating to obtain the best fit to the experimental data by varying the Fraction
Released and the first-order rate constant (k) using Equation D-4 and the following
relationship:
Page 96
E 0 = (Mass Applied) * (Fraction Released) * k
(C-6)
This analysis was conducted using Excel to solve the equations and plot the results. The best fit
was arrived at by visual comparison of the results of Equation D-4 with the extracted US EPA
(1994b) data, attempting to fit the Equation D-4 curve midway between the maximum and
minimum values of the data. In general, the height of the concentration curve is related
primarily to the DCM mass released, and the length and shape of the decay portion of the curve
is closely related to the first-order rate constant, k. The resulting fit for the BIX Spray-On
Stripper product is shown in Figure D-1 and the fit for the Strypeeze product (brush application)
is shown in Figure D-2. In each figure, the underlying eight exponentials are shown in the lower
part of the figure, with the sum shown as the fitted, dashed line. The parameters for these two
DCM cases are shown in Table D-2.
Figure D-1. Model Fit to MRI (US EPA, 1994b) Data for BIX Spray-On (Spray Application).
Page 97
Figure D-2. Model Fit to MRI (US EPA, 1994b) Data for Strypeeze (Brush Application).
Table D-2. Fitted Parameters to the US EPA (1994b) Study Results for the Two DCM-Containing Paint
Strippers.
Mass of Product
Applied, g
DCM Mass
Applied, g
DCM Fraction
Released
First-Order Rate
Constant, Hour-1
BIX Spray-On Stripper
540
495
0.66
10
Strypeeze
722
121
0.33
10
Product
A numerical integration of the fitted sum of 8 exponentials shown in Figures D-1 and D-2 was
performed by using the average concentration for each one-minute interval and conducting a
mass-balance calculation for the test chamber, accounting for the mass in the chamber and the
mass that has been removed through ventilation. The resulting mass released from the product
as a function of time is shown in Figures D-3 and D-4 for BIX Spray-On and Strypeeze stripper,
respectively.
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111 minutes
Figure D-3. Theoretical Cumulative Mass of DCM Released for BIX Spray-On Stripper.
111 minutes
Figure D-4. Theoretical Cumulative Mass of DCM Released for Strypeeze Stripper.
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The NMP-containing product, Wood Finishers Pride, was fit in a similar manner as the two
DCM-containing products. A double exponential was needed to provide an acceptable fit to the
data, due to the lower volatility of NMP and the resulting longer tail to the emission profile
shown in the US EPA (1994b) study, runs 10, 11, and 12. The first exponential is used to
represent the rapid rise during application and the second exponential is used to capture the
extended slower release of chemicals from the surface after application. The study applied
the product in eight, approximately 30-second applications, followed by an approximately
10.5-minute wait time prior to the start of the subsequent application, resulting in about
11 minutes between applications. The emissions from each application are represented by a
double exponential, with each pair of exponential identical to the other seven pairs, but with a
different start time set at the midpoint of the application period. Based on this approach, the
start times of the eight NMP double exponentials are 0.25, 11.25, 22.25, 33.25, 44.25, 55.25,
66.25, and 77.25 minutes from the start of the stripping activity, respectively.
For Wood Finishers Pride, the fitting process involved:
1.
2.
3.
Extracting measured concentration values from the US EPA (1994b) data and coplotting the points with Equation D-5. The concentration values were extracted for
runs 10, 11, and 12 at each 0.5-hour time point as well as the peak value. This
resulted in 11 data points per run.
Calculating the mass of NMP applied during the test and assigning 1/8th of the
applied mass to each of the eight double exponentials.
Iterating to obtain the best fit to the experimental data by varying the Fraction
Released and the first-order rate constant (k) using Equation D-5 for the first and
the second exponential and the following relationships:
E 01 = (Mass Applied) * (Fraction Released in the 1st Exponential) * k 1
(D-7)
E 02 = (Mass Applied) * (Fraction Released in the 2nd Exponential) * k 1
(D-8)
Excel was used to solve Equation D-5 and plot the results. The best fit was arrived at by visual
comparison of the results of Equation D-5 with the extracted US EPA (1994b) data, attempting
to fit the Equation D-5 curve midway between the maximum and minimum values of the data.
The resulting fit for is shown in Figure D-5, with the underlying eight exponentials shown in the
lower part of the figure, with the sum shown as the fitted, dashed line. The parameters for the
Wood Finishers Pride case are shown in Table D-3.
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Figure D-5. Model Fit to MRI (US EPA, 1994b) Data for Wood Finishers Pride (Brush Application).
Table D-3. Fitted Parameters to the US EPA (1994b) Study Results for Wood Finishers Pride.
Product
Wood
Finishers
Pride
1st Exponential
2nd Exponential
Mass of
NMP Mass
First-Order
First-Order
Product
Applied, g NMP Fraction Rate Constant, NMP Fraction Rate Constant,
Applied, g
Released
Released
Hour-1
Hour-1
866
390
0.02
10
0.24
0.05
In a similar manner to the numerical integration described above, a numerical integration of

the fitted sum of 8 exponentials shown in Figure D-5 yielded the mass released relationship
shown in Figure D-6 for Wood Finishers Pride.
Page 101
Figure D-6. Theoretical Cumulative Mass of NMP Released from Wood Finishers Pride.
Discussion and Conclusions

From the exponential fits to the US EPA (1994b) data, we estimate that 66 percent of the
applied DCM in the spray product (Figure D-1) was released to air, versus 33 percent of the
applied DCM in the brush product (Figure D-2). We estimate that virtually all of the 66 and
33 percent of the DCM mass will be released by two hours after application for the spray and
brush product, respectively, very shortly after the last scraping is finished, due to the higher
volatility. Thus, the concentration-decline part of Figures D-1 and D-2, after the peak, is due
almost exclusively to ventilation rather than to declining emissions, and therefore, these
exposures could be virtually eliminated through ventilation.
On the other hand, for the NMP brush-on product, only about two percent of the applied mass
is accounted for by the first exponential. For the second exponential, the percent accounted
for depends on the duration of the activity and resulting exposure, as the off-gassing after
application is very slow. Three hours after the start of the run, about 4.7 percent of the applied
NMP mass is accounted for by the two exponentials (two percent by the first exponential and
2.7 percent by the second exponential). At 24 hours, about 18 percent of the applied NMP
mass was accounted for (two percent by the first exponential and 16 percent by the second
exponential). Integrating the two exponentials to time of infinity yields a prediction of a total
potential release of 26 percent of the applied NMP. US EPA (1994b) had no NMP spray-on
stripper products, so a release fraction from a spray could not be derived from measured data.
Instead, the ratio of DCM spray to brush-on release fractions, 0.66/0.33, was applied to the
brush-on NMP release fraction of 0.26 to estimate a release fraction of 0.52 for NMP in a sprayon product.
Factors that should be considered in applying these findings to a model-based approach using
MCCEM include the effect of varying the product use behavior and the effect of the quantity of
the chemical applied. It appears that the off-gassing rate is a function of the mass applied and
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the duration of application; based on the limited data available, the emission rate does not
exhibit significant inhibition of volatilization due to increased concentrations in the range of air
concentrations observed in the US EPA (1994b) study. If this holds true, then the results of this
analysis can be applied to a variety of product use behavior by modifying MCCEM to represent
this behavior. MCCEMs capability of representing the application as an incremental
exponential may further improve the representativeness of the predicted concentrations.
SENSITIVITY ANALYSIS FOR INHALATION SCENARIOS

For this analysis, each input that could be measured on a continuum (e.g., emission rate,
airflow rate) was first halved and then doubled while holding all others at their base-case
values. For an input to which the model output is directly and linearly proportional, and for
which the exposure measure for the base case is denoted as X, the result for the halved case
would be X and the result for the doubled case would be 2X. Computing and averaging the
two differences from the base case gives the following result:
([X-1/2X] + [2X-X]) / 2) / X = or 75%
(D-9)
For an input that cannot be varied over a continuum, or that can be dealt with only discretely or
perhaps dichotomously (e.g., in the use zone or not at certain key times), the above procedure
can still be used but the sensitivity measure reduces to:
|Y-X| / X (expressed as a percent)
(D-10)
Where Y is the output associated with the change in location pattern from the base case.
INHALATION EXPOSURE SCENARIO INPUTS

Model Inputs
Method of Application. A review of product labels and technical data sheets indicates that
paint stripping products can be applied using either brush-on or spray-on (i.e., aerosol or
trigger-pump) application methods. Exposures were assessed for both brush-on and spray-on
products due to differences in chemical release characteristics, NMP weight fraction of
products, application rates, and time required for application, as discussed below.
Application Amount (Product Mass). The product application mass (grams of product) was
determined using application rates (g/ft2) calculated from the chamber tests in US EPA (1994b)
and the surface area of objects to be stripped (ft2). Surface areas were selected so that the
resulting product mass corresponded approximately to central (near the median) and upperend (near the 90th percentile) estimates for the amount of paint stripper product used per
event from the large nationwide Abt (1992) survey, as reported in EFH Table 17-20. EFH
reports a median value of 32 fluid ounces or gallon. Conversion to metric units
(3.75 L/gallon) and consideration of the nominal product density (~1.1 g/cm3) (calculated from
Page 103

Brown, 2012) yields a product mass on the order of 1,000 g as a central estimate. An upperend application amount (~80th percentile) from the same survey is 80 ounces or 2,500 g.
Similarly, the small Riley et al. (2001) survey reported 32 ounces as the median amount of paint
stripper product used. Specific product masses used in this assessment for the brush-on scenarios
were 1,080 g for Scenarios 1 and 2, 2,700 g for Scenario 3, and 3,888 g for Scenarios 7 and 8.
Product masses for the spray-on scenarios were 810 g for Scenarios 4 and 5 and 2,025 g for
Scenario 6.
As previously mentioned, the application amounts assumed in this assessment for Scenarios 1
through 6 are a product of application rates calculated from the US EPA (1994b) experiments
and the surface area of objects to be treated. The calculated application rate was ~108 g/ft2 for
the brush-on application (866 g of product applied to eight ft2). There were no US EPA (1994b)
applications involving NMP-containing spray-on strippers. Consequently, the DCM brush/spray
ratio (540 g/722 g) was applied to the NMP brush amount of 108 g/ft2 to estimate the NMP
spray application, resulting in an estimated NMP spray product application rate of 81 g/ft2
(648 g of product applied to eight ft2). These application rates are similar to those
recommended on the Savogran Company website for paint strippers in general, one gallon per
50 to 100 ft2 (~42 to 83 g/ft2 based on a nominal density of 1.1 g/cm3) (Savogran, 2012).
The applied surface areas selected for central and upper-end values were 10 and 25 ft2,
respectively. The upper-end surface area is 2.5 times higher than the central surface area and
provides sufficient distinction from the central case. Application targets with surface areas
close to the two specified surface areas (10 and 25 ft2) were used in the exposure scenarios to
reflect real-world situations. A coffee table with nominal dimensions of 4 feet 2.5 feet for the
top surface was selected for the central case (10 ft2) (Abbas, 2012) and a chest of drawers with
nominal dimensions of 4 feet high by 2.5 feet wide by 1.5 feet deep (American Unfinished
Furniture, 2012 shows an illustrative chest of drawers with nearly the same dimensions) was
selected for the upper-end case (4 2.5 ft2 for front + 2.5 1.5 ft2 for top + 2 4.5 1.5 ft2 for
sides 25 ft2). For the bathroom scenario, a bathtub surface area of 36 ft2 was calculated
assuming nominal dimensions of five feet wide by 2.5 feet deep by 1.5 feet high.
Stripping Sequence. The sequence chosen to characterize product application was intended to
be consistent with labeling instructions. The stripping event consisted of an initial stripping
sequence (apply-wait-scrape) followed by a second stripping sequence. The NMP product
labels advise that the stripper be applied to the object followed by a wait period of at least 30
minutes (up to 24 hours). The labels generally do not indicate that the product needs to be
applied in small sections. The application sequence is also supported by Internet discussion
forums suggesting that an advantage to NMP formulations is that they allow the user more
flexibility because the product will not evaporate (OldHouseOnline, 2012).
The application time was derived from the US EPA (1994b). From the protocol description in
that report, it was deduced that the NMP stripper was brush-applied at a rate of two ft2/minute
and spray applied at a rate of four ft2/minute. It was further assumed that the scrape time was
double the application time, meaning that the surface was scraped at a rate of one ft2/minute.
Page 104

For the bathtub case (Scenarios 7 and 8), because of the larger surface area, the application and
scrape times were scaled up proportionally to 18 and 36 minutes, respectively. The scaled
initial and secondary application times, wait times, and scrape times are summarized in
Table D-4.
Table D-4. Time Schedule for Paint Stripping with Repeat Application.
Scenario
Elapsed Time From Time Zero, Minutes (Product User Location)

Apply 1
Wait 1
Scrape 1
Apply 2
0-5
5-35 (ROH)
35-45
45-50
workshop, central tendency (workshop)
(workshop) (workshop)
scenario
Wait 2
Scrape 2
50-80
(ROH)
80-90
(workshop)
workshop, upper-end
scenario for user
0-5
5-35
35-45
45-50
50-80
80-90
(workshop) (workshop) (workshop) (workshop) (Workshop) (workshop)
workshop, upper-end
scenario for non-user
0-12.5
12.5-42.5 42.5-67.5
67.5-80
(workshop)
(ROH)
0-2.5
workshop, central tendency (workshop)
scenario
2.5-32.5
(ROH)
32.5-42.5
42.5-45
80-110
(ROH)
110-135
(workshop)
45-75
(ROH)
75-85
(workshop)
workshop, upper-end
scenario for user
0-2.5
2.5-32.5
32.5-42.5
42.5-45
45-75
75-85
(workshop) (workshop) (workshop) (workshop) (workshop) (workshop)
workshop, upper-end
scenario for non-user
0-6.25
6.25-36.25 36.25-61.25 61.25-67.5 67.5-97.5 97.5-122.5
(workshop)
(ROH)
(ROH)
(workshop)
0-18
(bathroom)
bounding for user and nonuser; C sat = 1,300 mg/m3
18-48
(ROH)
48-84
84-102
(bathroom) (bathroom)
102-132
(ROH)
132-168
(bathroom)
0-18
(bathroom)
bounding for user and nonuser; C sat = 640 mg/m3
18-48
(ROH)
48-84
84-102
(bathroom) (bathroom)
102-132
(ROH)
132-168
(bathroom)
Amount of Chemical Released. The amount of chemical released during and after the stripping
event is the product of three parameters: amount applied (discussed above), weight fraction of
chemical in the applied product, and fraction of the chemical that is released to indoor air.
From the product list developed by Brown (2012), the median NMP weight fraction was
determined to be 0.25 for the brush-on application (range of 0.03 to 0.53) and 0.44 for the
spray-on application (range of 0.28 to 0.53). The weight fractions were determined from the
Brown (2012) spreadsheet by using only products intended for consumer use (i.e., adhesive
removers, paint brush cleaners, deglossers, and industrial/commercial use products were
Page 105

removed). The application method (brush-on or spray-on) for a product was determined by
examining the product labels/technical data sheets and product names, and through Internet
research. If an application method could not be determined through the above methods, then
the product was assigned to the brush category, as most paint stripping products are applied by
the brush method, and formulations such as semi-paste would be difficult to apply using a
sprayer. If a weight fraction range was provided in the product list, then the average of the
minimum and maximum weight fractions was used in calculations. The weight fractions were
not weighted to reflect the market share of products.
Analysis of the US EPA (1994b) data (see Estimation of Emission Profiles for Paint Removers/
Strippers) indicates NMP release fractions of 0.26 for brush-on and 0.52 for spray-on. The
resultant mass applied for different application targets is summarized in Table D-5.
Table D-5. NMP Mass Released, by Application Target and Method.
Target (Surface Area)
and Method
Application
Rate, g/ft2 a
Weight
Fractionb
Release Fraction
NMP Mass
Released, g
Coffee table (10 ft2)

Brush-on
Spray-on
108
81
0.25 | 0.50
0.44 | 0.53
0.26
0.52
70.2 | 140.4
185.3 | 223.2
Chest of drawers (25 ft2)

Brush-on
Spray-on
108
81
0.50
0.53
0.26
0.52
351.0
558.1
Bathroom tub (36 ft2)

Brush-on
108
0.5
0.26
505.4
Reflects repeat application for each segment.

For the coffee-table case, two weight fractions are given, one for central and one for upper-end.
Airflow Rates and Volumes. The model run requires conceptualization of a residence in terms
of the number of zones and their respective volumes. The airflow rates needed to model the
central and upper-end cases described above are: (1) rates between indoors and outdoors for
each zone; and (2) rates between the zones. Airflow for tub stripping in the bathroom, which is
somewhat more complex to conceptualize, is described below, after the central and upper-end
cases.
For the central and upper-end cases, the house in which the modeled stripper application occurs
is conceptualized as having two zones: (1) the workshop where application occurs; and (2) the
ROH. The house volume chosen for the model runs, 492 m3, was the central value listed in the
EFH. The volume assigned to the in-house workshop area was 54 m3, corresponding to 12 feet
20 feet with an eight-foot ceiling (20 12 8 = 1,920 ft3 or ~54 m3). This room volume is
similar to the value reported in Riley et al. (2001) for the mean volume of the room used for
paint stripping (51 m3). The volume for the ROH, 438 m3, is determined by subtraction (492 to
54 m3). For the bathroom scenario, the bathroom volume was set at nine m3 for consistency
with that reported in a CDC/NIOSH case (CDC, 2012).
Page 106
The indoor-outdoor airflow for any zone of the house is governed by the choice of air exchange
rate, in ACH. The central and low-end values for the air exchange rate, 0.45/hour and
0.18/hour that were used in assigning the indoor-outdoor airflow rate for the ROH are the
mean and 10th percentile values, respectively, from the EFH. (Note that a low-end ACH would
be expected to contribute to upper-end concentration estimates.) For the workshop, it was
assumed that multiple windows were opened. The indoor-outdoor airflow rate assigned to this
zone, 68 m3/hour, was obtained by multiplying the room volume of 54 m3 by the 90th percentile
(1.26/hour) of the air-exchange-rate distribution from the EFH, thought to be a reasonable
representation of the open-window case.
The use of open windows in the room of use is supported by both label instructions and survey
data. Even though NMP is not highly volatile, the majority of the labels indicate that adequate
ventilation must be used and that to prevent build-up of vapors, windows and doors should be
opened to achieve cross ventilation. Additionally, Pollack-Nelson (1995) reported that an
average of 70.7 percent of paint stripper users (all products) kept a window or door open
during use based on data from the WESTAT (1987) survey and that 88.8 percent of paint
stripper users (all products) kept a window or door open during use based on data from the Abt
(1992) survey. The increase was significant between the survey years. The more recent, small
Riley et al. (2001) survey also indicates that the majority of paint stripper users (55 percent)
opened a window. Both Pollack-Nelson (1995) and Riley et al. (2001) also reported that some
users used an exhaust fan during the stripping process, which would affect the air exchange
rate. The percentage of fan users was not reported in Pollack-Nelson (1995). The Riley et al.
(2001) data suggest that only ~27 percent of the users who worked indoors used an open
window and fan. Due to the small percentage of people who used a fan, coupled with the fact
that a couple of labels indicate that the product should be kept away from heat, sparks, flame,
and all other sources of ignition, none of the scenarios were assumed to involve use of a fan in
the room of product use.
The interzonal airflow rate was estimated using the following algorithm, presented in US EPA
(1995):
Q = (0.078 + 0.31*ACH) * house volume
(D-11)
where Q is the interzonal airflow rate, in m3/hour, and ACH is the air exchange rate, in 1/hour.
Substitution of the central air exchange rate of 0.45/hour and the house volume of 492 m3
yields an estimated interzonal airflow rate of 107 m3/hour. The corresponding number for the
upper-end case, with an air exchange rate of 0.18/hour, was 65.8 m3/hour. Figure D-7 depicts the
volumes and airflows that were used for the workshop scenarios.
Page 107

Values for Upper -end
Concentration Scenarios
Central Values
68
m3/hr
Room of
107
Use
3
(54 m3) m /hr
Rest of
House
(438 m3)
197
m3/hr
Room of
65.8
Use
3
(54 m3) m /hr
68
m3/hr
Rest of
House
(438 m3)
78.8
m3/hr
denotes air flow
Figure D-7. Zone Volumes and Airflow Rates for Workshop Scenarios.
As previously noted, the bathroom case (Figure D-8) is more complex. Because the user is
working in close proximity to the target (bathtub) for an extended period, a third zone (source
cloud) was created within the bathroom to represent the NMP concentrations in the vicinity of
the tub; this is a virtual zone, with no physical boundaries. The airflow rate between the cloud
and the rest of the bathroom was based on work by Matthews et al. (1989), who determined
experimentally that such an airflow could be estimated as the product of the room air velocity
(in m/hour) and the entry/exit surface area (in m2). Using their suggested value of 65 m/hour
for air velocity together with an assumed entry/exit surface area of five ft by two ft (10 ft2 or
0.93 m2) yields an estimated airflow rate of 60 m3/hour between the source cloud and the rest
of the bathroom. Based on professional judgment, the interzonal airflow rate between the
bathroom and ROH of the house was assumed to be ~2/3 lower than that for the workshop
central case, given the small bathroom volume. The indoor-outdoor airflows were based on an
assumed air exchange rate of 0.18 ACH.
1.6
m3/hr
Rest of
Bathroom
(8 m3)
35
m3/hr
Rest of
House
(483 m3)
86.9
m3/hr
60
m3/hr
Source Cloud
(1 m3)
denotes air flow
Figure D-8. Zone Volumes and Airflow Rates for Bathroom Scenario.
Locations of Exposed Individuals. Two location patterns were specified, one for a product user
and one for a non-user. The user was assumed to be in the work area for stripper application
and scraping for all scenarios. For the waiting phase of the stripping process, the user was
assumed to be in the ROH as a central-tendency assumption for the user (Scenarios 1 and 4), in
Page 108

the workshop as an upper-end assumption for the user (Scenarios 2 and 5), and in the ROH of
the house for Scenarios 3, 6, 7, and 8, which were developed to model upper-end
concentrations primarily for the non-user. The user was placed in the ROH during the waiting
phase for the central assumption because the user is assumed to be aware of potential
inhalation health concerns from using paint strippers based on label warnings (Vapor
Harmful) on some labels (which are often for products containing multiple active ingredients,
not solely NMP), and because the Riley survey (Riley et al., 2001) reported that 65 percent of
users reported taking breaks outside the work area. Breaks typically involved a specific break
activity and location, such as going to the kitchen and making a sandwich, or going outside to
do yard work. For the upper-end Scenarios 2 and 5, it was assumed that the user would stay in
the workshop, based on the fact that some people do not read/skim labels (~28% in 1990;
Pollack-Nelson, 1995) and that the Riley survey (Riley et al., 2001) indicated that 20 percent of
participants reported taking breaks inside the work area. For all scenarios, the user was
assumed to leave the workroom immediately after the stripping process, based on the WESTAT
(1987) and Abt (1992) surveys with a median value of zero minutes spent in the room after
using the product (US EPA, 2011c).
The non-user was assumed to be in the ROH throughout the model run, as was the user for the
portion of the run after all applying/scraping was completed. For the bathroom scenario, the
user was assumed to be in the ROH during the wait times.
It was further assumed that the scrapings were removed from the house as soon as scraping
was completed for the last segment. The implication for modeling purposes is that any
remaining NMP emissions would be truncated at that time.
Saturation Concentration Constraint. As discussed above, Scenarios 7 and 8 were used to
estimate NMP concentrations for conditions similar to those reported in a CDC/NIOSH
occupational exposure case to a DCM paint stripper (CDC, 2012); as a result, the modeled NMP
concentrations for these scenarios may approach the saturation concentration. For the
purposes of this assessment, the saturation concentration was calculated based on reported
vapor pressures for NMP, using the ideal gas law to convert the reported vapor pressure into
airborne concentrations. The literature-reported vapor pressures for NMP vary widely. A
sampling of the reported vapor pressures is provided in Table D-6, along with the calculated
saturation concentrations. As apparent in the table, there is a fairly broad range of reported
values: from 1,287 to 1,871. A saturation concentration of 1,300 mg/m3 (vapor pressure =
0.24), within the range of reported values, was selected and used in Scenario 7.
Table D-6. Literature-Reported Vapor Pressure Values for NMP.
Vapor Pressure
at 20 C (Torr)
Saturation Concentration at 20 C
(mg/m3)
0.237
1,286.7
BASF Product Information(BASF, 2007)
0.29
1,572.5
Cisco Chemicals MSDS (CISCO, 2011)
0.3
1,626.7
Lyondell MSDS (Lyondell, 2004)
Source
Page 109

0.24
1,301.4
Taminco MSDS (Taminco, 2011)
0.345
1,870.7
EPA NMP Assessment Memo (US EPA, 2006)
0.293
1,586.2
WHO Report (WHO, 2001)
MCCEM prevents the airborne concentrations of NMP from exceeding NMPs saturation
concentration through the input of a saturation constraint value. The model normally will apply
the emission rates specified by the user without regard to the chemicals saturation
concentration in air; in other words, the saturation concentration could be exceeded. If the
user selects the saturation constraint, then the model will check to ensure that the saturation
concentration is not exceeded, adjusting the emission rate as needed to meet this constraint.
In such cases, the same chemical mass ultimately will be released, but at a slower rate than
implied by the user's source model.
The following equation is used to estimate the value for the saturation concentration:
C sat = (VP/760 mm Hg/atm MW 1,000 mg/g 1,000 L/m) / (R T)
(D-12)
where:
C sat = saturation concentration (mg/m)
VP = vapor pressure (mm Hg)
MW = molecular weight (g/mole)
R = gas constant = 0.0821 liter atm/mole K
T = temperature of the air (K)
At each time step, MCCEM checks whether the current value for the emission rate results in an
indoor concentration that exceeds C sat . If so, then the emission rate is reduced to a value that
results in the indoor concentration equaling C sat . In such a case, MCCEM keeps track of the
cumulative mass that has been "subtracted" to meet the C sat constraint; release of this
accumulated "excess" mass is initiated at a later point in time, when the modeled
concentration otherwise would be below the C sat value. This procedure is continued until all
excess mass has been released, unless the end of the time period for the model run is
encountered first.
NMPs saturation concentration is affected by the level of relative humidity. An NMP Initial
Assessment Report (OECD, 2007) by the OECD 5 reported that several studies measured the
relationship between vapor pressure for NMP and relative humidity and reported the following:
It is noteworthy that NMP exists in various proportions of vapor and aerosol
depending on the concentration, temperature and humidity. The maximum vapor
phase at room temperature is 1.286 mg/l (315 ppm) in dry air (0% relative
humidity), 0.525 mg/l (128 ppm) at normal animal room humidity (50% relative
5
OECD, 2, rue Andr Pascal, 75775 PARIS Cedex 16, France. www.oecd.org.
Page 110

humidity) and 0 mg/l (0 ppm) in humidity saturated air (100% relative humidity
BASF AG, 1995c, b, a, 1989, 1992).
Based on the cited findings, the OECD report concludes:
Thus, the vapor saturation of NMP under normal conditions is considered to be in
the range of 0.48 - 0.64 mg/l (120 - 160 ppm) depending on humidity and
temperature.
The studies and associated data cited by OECD were conducted by BASF AG; however, the
studies are unpublished and are not readily available. To examine this potential relative
humidity impact, Scenario 8 imposes a saturation concentration constraint of 640 mg/m3,
representing the upper-end saturation concentrations associated with "normal humidity
conditions." This concentration corresponds to an estimated RH, calculated by interpolation, of
approximately 42 percent.
INHALATION MODEL OUTPUTS AND EXPOSURE CALCULATIONS

Personal Concentrations
Peak TWA concentrations for different averaging periods, described below, were calculated
from the one-minute averages for both the user and non-user based on their respective
personal concentration time series. The calculations took into account the possibility that the
user can change zones within a one-minute interval (e.g., at an elapsed time of 6.25 minutes).
The personal concentration was calculated for each one-minute interval in the modeling period
(24 hours or 1,440 one-minute intervals) as follows:
For each time interval, i to i +1, for i = 0 to 1,440:
(D-13)
Where:
PC i,i+1 = the personal concentration over the time interval i to i +1
C 1,i and C 1,i+1 = the concentrations in the use zone at times i and i+1, respectively
C ROH,i and C ROH,i+1 = the concentrations in the ROH zone at times i and i+1, respectively
F i,i+1 = the fraction of time spent in the use zone during the time interval i to i +1
These calculations, illustrated in Figure D-9, were implemented for each of the eight scenarios.
Page 111

Time Interval
= (D5 + D4) / 2
Fraction of Time
Spent in Use Zone
= H5*J5 + I5*(1-J5)
Figure D-9. Example of the Personal Concentration Calculation as Defined in Equation C-13.
TWA Concentrations
In addition to the maximum one-minute concentration and the 24-hour average concentration
to which the user and non-user were exposed, a peak TWA personal concentration also was
calculated for each of the following averaging periods: 10 minutes, 30 minutes, one hour, four
hours, and eight hours. The peak TWA concentration for any averaging period was defined as
the highest value of the consecutive running averages for that averaging period. For any
averaging period, there are (1,440-length of the averaging period) TWA concentration values
within the 24-hour (1,440-minute) time series. For example, there are 1,430 10-minute
averaging periods (1,440-10), the first of which is for time 0 to 10 minutes, the second of which
is for time one to 11 minutes, and so on, with the last for time 1,430 to 1,440 minutes. The
running averages for each averaging period were computed in an Excel spreadsheet, from
which the maximum value was determined.
Modeling Results
The zone and personal concentrations predicted by MCCEM are presented in Figures D-10
through D-13 at the end of this section. Figure D-10 shows the zone and user personal
concentration results for Scenario 1 (brush application in the workshop with central parameter
values; top two figures) and Scenario 4 (spray application in the workshop using central
parameter values). The non-user personal concentrations are assumed to be those in the ROH.
As indicated in Figure D-10, the peak concentrations are higher for the spray application case
than those for the brush application case, even though the mass of product applied is higher for
the brush application case (1,080 g stripper applied for the brush application case as compared
to 810 g for the spray application). This difference is explained primarily by two factors: (1) the
weight fraction of NMP in the stripper product (0.44 for the spray product vs. 0.25 for the brush
product); and (2) the potential release fraction of the mass emitted (assumed to be the
52 percent for spray and 26 percent for brush applications). This release is termed the
Page 112

"potential release" because NMP emissions take place over an extended period (>24 hours)
and, consequently, much of the release is truncated due to earlier completion of the stripping
activity and removal of the scrapings. As a result, the ratio of NMP mass emitted for
spray/brush application is ~2.4 (1,080 g 0.25 0.26 = 70 g for the brush activity vs. 810 g
0.44 0.52 = 190 g for the spray activity). As described in Section 2.1.2, the release fraction is
based on analysis of chamber data from US EPA (1994b) (see the section on Estimation of
Emission Profiles for Paint Removers/Strippers in Appendix C) for NMP for the brush application
and extrapolation to the spray application using a relationship for DCM derived from US EPA
(1994b), because no chamber data are available for the NMP spray application.
Figure D-11 shows the zone and user personal concentration results for Scenarios 2 and 5
(brush and spray application, respectively) for the workshop with parameter values selected to
estimate upper-end concentrations for the user. For these scenarios, the ratio of peak
concentrations between the spray and brush application cases is 1.6.
Figure D-12 shows the zone and user personal concentration results for Scenarios 3 and 6
(brush and spray application, respectively) for the workshop with parameter values selected to
estimate upper-end concentrations for the non-user; the results also indicate a pronounced
increase in exposure for the user.
Figure D-13 shows the air concentrations for the bathroom case, bathroom bathtub stripping
activity. Scenario 7, which imposes a saturation concentration constraint of 1,300 mg/m3, has
modeled peak concentrations of 1,300 mg/m3 (320 ppm) and 920 mg/m3 (230 ppm) for the
source cloud and bathroom, respectively. Scenario 8, which imposes a saturation
concentration constraint of 640 mg/m3, has modeled peak concentrations of 640 mg/m3
(160 ppm) and 560 mg/m3 (140 ppm) for the source cloud and bathroom, respectively. For
both scenarios, the predicted airborne concentrations reach the saturation concentration in the
source cloud, but remain lower than the saturation concentration in the bathroom.
Page 113
(Non-user assumed to be in ROH)
a) Scenario 1, Brush Applied
b) Scenario 4, Spray Applied

Figure D-10. Modeled NMP Concentrations for Scenarios 1 and 4, Stripper Application in Workshop using Parameter Values selected for
Central Tendency Exposure.
Page 114

Figure D-11. Modeled NMP Concentrations for Scenarios 2 and 5, Stripper Application in Workshop using Parameter Values selected for
Upper-end User Exposure.
Page 115

Figure D-12. Modeled NMP Concentrations for Scenarios 3 and 6 Stripper Application in Workshop using Parameter Values selected for
Upper-end Non-User Exposure.
Page 116
Csat = 1300 mg/m3
Csat = 1300 mg/m3
a) Scenario 7, Saturation Concentration Constraint at 1,300 mg/m3
Csat = 640 mg/m3
Csat = 640 mg/m3
b) Scenario 8, Saturation Concentration Constraint at 640 mg/m3

Figure D-13. Modeled NMP Concentrations for Scenarios 7 and 8, Brush Application in Bathroom using Parameter Values selected for Upperend to Bounding User and Non-User Exposures.
Page 117
MCCEM INHALATION MODELING CASE SUMMARIES

NMP Summaries
Formula:
CASRN:
Molecular Weight:
Density:
Appearance:
Melting Point:
Boiling Point:
Vapor Pressure (at 20 C):
Conversion units: 1 ppm =
Saturation Concentration:
C5H9NO
872-50-4
99.13 g/mol
1.028 g/cm2 (liquid)
clear liquid
-24 C = -11 F = 249 K
203 C = 397 F = 476 K
~32.4 Pa = 0.243 Torr = 0.00032 atm = 0.0047 psi
4.054397 mg/m3
~1,300 mg/m3
NMP Scenario 1. Coffee Table, Brush-On, Workshop, User in ROH during wait time, 0.45 ACH,
0.25 Weight Fraction
MCCEM Input Summary
Application Method:
Brush-on
Volumes:
Workshop volume = 54 m3
ROH volume = 492 54 = 438 m3
Airflows:
Workshop-outdoors
ROH-outdoors
Workshop-ROH
68 m3/h
197.1 m3/h (0.45 ACH)
107 m3/h
NMP Mass Released:

Coffee table = 10 sq ft surface area
Applied product mass = 108 g/sq ft = 1,080 g
Applied NMP = 1,080 g 0.25 (wt fraction) = 270 g
Total NMP mass released (both exponentials) = 1,080 g 0.25 (wt fraction) 0.26 (release
fraction, theoretical) = 70.2 g
For each of the 2 applications:
k 1 = 10/hr
% Mass for Exponential 1 = 2% = 0.02*1,080*0.25 (wt fraction) * 0.5 (half per application)
= 2.7 g or 7.7% of released NMP
E 01 = Mass * k 1 = 2.7*10 = 27 g/hr (NOTE: only k and Mass are needed as MCCEM inputs)
Page 118

k 2 = 0.05/hr
= 32.4 g
E 02 = Mass * k 2 = 32.4*0.05 = 1.624 g/hr (NOTE: only k and Mass are needed as MCCEM inputs)
Application Times and Activity Patterns:
Elapsed Time from Time Zero, Minutes (Product User Location)
Episode
1) Coffee Table, Brush-On,
Workshop, User ROH during wait
time, 0.45 ACH, 0.25 Weight
Fraction
Apply 1
Wait 1
Scrape 1
Apply 2
Wait 2
Scrape 2
0-5 (Use)
5-35
(ROH)
35-45
(Use)
45-50
(Use)
50-80
(ROH)
80-90
(Use)
User in ROH at the end of Scraping 2

User in ROH for the remainder of the run (22 hours, 30 minutes)
Model Run Time:
0-24 hours
User takes out scrapings after 90 minutes, emissions truncated
MCCEM Results Summary
Personal Exposures (maximum values over first 24 hours):
Individual
User
Other
Individual
User
Other
1 min
32.7
7.3
1 min
8.1
1.8
10 min
30.5
7.3
In mg/m3
30 min
1 hour
15.0
13.3
7.2
6.9
4 hour
6.6
4.6
8 hour
3.8
2.7
24 hour
1.3
0.9
10 min
7.5
1.8
In ppm
30 min
1 hour
3.7
3.3
1.8
1.7
4 hour
1.6
1.1
8 hour
0.9
0.7
24 hour
0.3
0.2
Plots:
Page 119
Page 120

NMP Scenario 2. Coffee Table, Brush-On, Workshop, User in Workshop during wait time, 0.45
ACH, 0.5 Weight Fraction
MCCEM Input Summary
Application Method:
Brush-on
Volumes:
ROH volume = 492 54 = 438 m3
Airflows:
Workshop-outdoors
ROH-outdoors
Workshop-ROH
68 m3/h
197.1 m3/h (0.45 ACH)
107 m3/h
NMP Mass Released:

Coffee Table = 10 sq ft surface area
Applied product mass = 1,080 g
Applied NMP = 1,080 g 0.5 (wt fraction) = 540 g
fraction, theoretical) =140.4 g
k 1 = 10/hr
E 01 = Mass * k 1 = 5.41*10 = 54.1 g/hr (NOTE: only k and Mass are needed as MCCEM inputs)
k 2 = 0.05/hr
= 64.8 g
Episode
2) Coffee Table, Brush-On,
Workshop, User in Workshop
during wait time, 0.45 ACH, 0.5
Weight Fraction
Apply 1
Wait 1
0-5 (Use) 5-35 (Use)
Scrape 1
Apply 2
Wait 2
Scrape 2
35-45
(Use)
45-50
(Use)
50-80
(Use)
80-90
(Use)

Page 121
Model Run Time:

0-24 hours
Individual
User
Other
Individual
User
Other
1 min
93.9
14.6
1 min
23.1
3.6
10 min
92.0
14.5
In mg/m3
30 min
1 hour
82.0
64.8
14.3
13.7
4 hour
28.6
9.1
8 hour
15.3
5.5
24 hour
5.2
1.9
10 min
22.7
3.6
In ppm
30 min
1 hour
20.2
16.0
3.5
3.4
4 hour
7.1
2.3
8 hour
3.8
1.4
24 hour
1.3
0.5
Plots:
Page 122
Page 123

NMP Scenario 3. Chest, Brush-On, Workshop, User in ROH during wait time, 0.18 ACH, 0.5
Weight Fraction
MCCEM Input Summary
Application Method:
Brush-on
Volumes:
ROH volume = 492 54 = 438 m3
Airflows:
Workshop-outdoors
ROH-outdoors
Workshop-ROH
68 m3/h
78.8 m3/h (0.18 ACH)
65.8 m3/h
NMP Mass Released:

Chest = 25 sq ft surface area
Applied NMP = 2,700 g 0.5 (wt fraction) = 1,350 g
fraction, theoretical) =351 g
k 1 = 10/hr
E 01 = Mass * k 1 = 13.51*10 =135.1 g/hr (NOTE: only k and Mass are needed as MCCEM inputs)
k 2 = 0.05/hr
= 162 g
E 02 = Mass * k 2 = 162*0.05 = 8.1 g/hr (NOTE: only k and Mass are needed as MCCEM inputs)
Episode
Apply 1
3) Chest, Brush-On, Workshop,

User in ROH during wait time, 0.18
0-12.5
(Use)
Wait 1
Scrape 1
Apply 2
Wait 2
Scrape 2
12.5-42.5 42.5-67.5
(ROH)
(Use)
67.5-80
(Use)
80-110
(ROH)
110-135
(Use)

Page 124

Model Run Time:
0-24 hours
Individual
User
Other
1 min
202.2
39.2
10 min
182.0
39.2
In mg/m3
30 min
1 hour
147.9
98.4
39.0
38.3
Individual
User
Other
1 min
49.9
9.7
10 min
44.9
9.7
30 min
36.5
9.6
4 hour
59.1
31.2
8 hour
38.5
23.0
24 hour
14.7
9.4
In ppm
1 hour
24.3
9.4
4 hour
14.6
7.7
8 hour
9.5
5.7
24 hour
3.6
2.3
Plots:
Page 125
Page 126

NMP Scenario 4. Coffee Table, Spray-On, Workshop, User in ROH during wait time, 0.45 ACH,
0.44 Weight Fraction
MCCEM Input Summary
Application Method:
Spray-on
Volumes:
ROH volume = 492 54 = 438 m3
Airflows:
Workshop-outdoors
ROH-outdoors
Workshop-ROH
68 m3/h
197.1 m3/h (0.45 ACH)
107 m3/h
NMP Mass Released:

Applied product mass = 810 g
Applied NMP = 810 g 0.44 (wt fraction) = 356.4 g
Total NMP mass released (both exponentials) = 810 g 0.44 (wt fraction) 0.52 (release
k 1 = 10/hr
% Mass for Exponential 1 = 4% = 0.04*810 *0.44 (wt fraction) * 0.5 (half per application)
k 2 = 0.05/hr
= 85.54 g
Episode
Apply 1
4) Coffee Table, Spray-On,

Workshop, User in ROH during wait
Fraction
0-2.5
(Use)
Wait 1
Scrape 1
Apply 2
Wait 2
Scrape 2
2.5 -32.5 32.5-42.5

(ROH)
(Use)
42.5-45
(Use)
45-75
(ROH)
75-85
(Use)

Page 127
Model Run Time:

0-24 hours
Individual
User
Other
Individual
User
Other
1 min
88.8
19.1
1 min
21.9
4.7
10 min
82.7
19.1
In mg/m3
30 min
1 hour
40.2
33.5
18.8
18.0
4 hour
16.8
11.9
8 hour
9.6
7.1
24 hour
3.3
2.4
10 min
20.4
4.7
In ppm
30 min
1 hour
9.9
8.3
4.6
4.4
4 hour
4.2
2.9
8 hour
2.4
1.8
24 hour
0.8
0.6
Plots:
Page 128
Page 129

NMP Scenario 5. Coffee Table, Spray-On, Workshop, User in workshop during wait time, 0.45
MCCEM Input Summary
Application Method:
Spray-on
Volumes:
ROH volume = 492 54 = 438 m3
Airflows:
Workshop-outdoors
ROH-outdoors
Workshop-ROH
68 m3/h
197.1 m3/h (0.45 ACH)
107 m3/h
NMP Mass Released:

Applied product mass = 810 g
Applied NMP = 810 g 0.53 (wt fraction) = 429.3 g
Total NMP mass released (both exponentials) = 810 g 0.53 (wt fraction) 0.52 (release
k 1 = 10/hr
k 2 = 0.05/hr
= 103 g
E 02 = Mass * k 2 = 103*0.05 = 5.2 g/hr (NOTE: only k and Mass are needed as MCCEM inputs)
Episode
Workshop, User in workshop
during wait time, 0.45 ACH, 0.53
Weight Fraction
Apply 1
0-2.5
(Use)
Wait 1
Scrape 1
Apply 2
Wait 2
Scrape 2
2.5 -32.5 32.5-42.5

(Use)
(Use)
42.5-45
(Use)
45-75
(Use)
75-85
(Use)

Page 130
Model Run Time:

0-24 hours
Individual
User
Other
Individual
User
Other
1 min
151.2
23.0
1 min
37.3
5.7
10 min
148.2
23.0
In mg/m3
30 min
1 hour
131.8
104.6
22.6
21.7
4 hour
44.6
14.3
8 hour
23.9
8.6
24 hour
8.1
2.9
10 min
36.5
5.7
In ppm
30 min
1 hour
32.5
25.8
5.6
5.3
4 hour
11.0
3.5
8 hour
5.9
2.1
24 hour
2.0
0.7
Plots:
Page 131
Page 132

NMP Scenario 6. Chest, Spray-On, Workshop, User in ROH during wait time, 0.18 ACH, 0.53
Weight Fraction
MCCEM Input Summary
Application Method:
Spray -on
Volumes:
ROH volume = 492 54 = 438 m3
Airflows:
Workshop-outdoors
ROH-outdoors
Workshop-ROH
68 m3/h
78.8 m3/h (0.18 ACH)
65.8 m3/h
NMP Mass Released:

Chest = 25 sq ft surface area
Applied NMP = 2,025 g 0.53 (wt fraction) = 1,073.25 g
k 1 = 10/hr
% Mass for Exponential 1 = 4% = 0.04*2,025 *0.53 (wt fraction) * 0.5 (half per application)
k 2 = 0.05/hr
% Mass for Exponential 2 = 48% = 0.48*2,025 *0.53 (wt fraction) * 0.5 (half per application)
= 257.6 g
Episode
Apply 1
Wait 1
Scrape 1

Workshop, User in ROH during wait
Fraction
0-6.25
(Use)
6.25-36.25
(ROH)
36.2561.25
(Use)
Apply 2
Wait 2
61.25- 67.5-97.5
67.5 (Use) (ROH)
Scrape 2
97.5122.5
(Use)

User in ROH for the remainder of the run (21 hours, 57.5 minutes)
Page 133
Model Run Time:

0-24 hours
User takes out scrapings after 122.5 minutes, emissions truncated
Individual
User
Other
Individual
User
Other
1 min
316.3
61.5
1 min
78.0
15.2
10 min
299.0
61.4
In mg/m3
30 min
1 hour
242.1
151.9
61.1
59.9
4 hour
89.8
48.7
8 hour
57.4
35.7
24 hour
21.9
14.5
10 min
73.7
15.1
In ppm
30 min
1 hour
59.7
37.5
15.1
14.8
4 hour
22.1
12.0
8 hour
14.2
8.8
24 hour
5.4
3.6
Plots:
Page 134
Page 135

NMP Scenario 7. Bathtub, Brush-On, Bathroom + Source Cloud, User in ROH during wait time,
0.18 ACH, 0.5 Weight Fraction
MCCEM Input Summary
Application Method:
Brush-on
Volumes:
Bathroom Volume = 9 m3 (8 m3 after removing source cloud zone)
Source Cloud Volume = 1 m3
ROH volume = 492 9 = 483 m3
Airflows:
Bathroom-outdoors
Source cloud - bathroom
Source cloud - outdoors
ROH-outdoors
Bathroom-ROH
1.6 m3/h
60 m3/h
0
86.9 m3/h (0.18 ACH)
35 m3/h
NMP Mass Released:

Bathtub Chest = 36 sq ft surface area
k 1 = 10/hr
k 2 = 0.05/hr
= 233.3 g
Page 136

Episode
Apply 1
7) Bathtub, Brush-On, Bathroom +

Source Cloud, User in ROH during
0-18 (Use)
wait time, 0.18 ACH, 0.50 Weight
Fraction
Wait 1
Scrape 1
Apply 2
Wait 2
Scrape 2
18-48
(ROH)
48-84
(Use)
84-102
(Use)
102-132
(ROH)
132-168
(Use)

User in ROH for the remainder of the run (21 hours 12 minutes)
Model Run Time:
0-24 hours
Individual
User
Other
Individual
User
Other
1 min
10 min
In mg/m3
30 min
1 hour
4 hour
8 hour
24 hour
1,300
1,300
1,300
830.8
515.1
292.0
107.7
109.7
109.6
108.9
106.9
90.8
72.1
33.4
4 hour
8 hour
1 min
10 min
In ppm
30 min
1 hour
24 hour
320.6
320.6
320.6
204.9
127.0
72.0
26.6
27.1
27.0
26.9
26.4
22.4
17.8
8.2
Page 137

Plots:
Page 138

NMP Scenario 7. Bathtub, Brush-On, Bathroom + Source Cloud, User in ROH during wait time,
0.18 ACH, 0.5 Weight Fraction
MCCEM Input Summary
MCCEM saturation concentration constraint invoked at 640 mg/m3
Application Method:
Brush-on
Volumes:
Bathroom Volume = 9 m3 (8 m3 after removing source cloud zone)
Source Cloud Volume = 1 m3
ROH volume = 492 9 = 483 m3
Airflows:
Bathroom-outdoors
Source cloud - bathroom
Source cloud - outdoors
ROH-outdoors
Bathroom-ROH
1.6 m3/h
60 m3/h
0
86.9 m3/h (0.18 ACH)
35 m3/h
NMP Mass Released:

Bathtub Chest = 36 sq ft surface area
k 1 = 10/hr
k 2 = 0.05/hr
= 233.3 g
Page 139

Episode
Apply 1
7) Bathtub, Brush-On, Bathroom +

Source Cloud, User in ROH during
0-18 (Use)
wait time, 0.18 ACH, 0.50 Weight
Fraction
Wait 1
Scrape 1
Apply 2
Wait 2
Scrape 2
18-48
(ROH)
48-84
(Use)
84-102
(Use)
102-132
(ROH)
132-168
(Use)

User in ROH for the remainder of the run (21 hours 12 minutes)
Model Run Time:
0-24 hours
Individual
User
Other
Individual
User
Other
1 min
640.0
64.8
1 min
157.9
16.0
10 min
640.0
64.8
In mg/m3
30 min
1 hour
640.0
580.3
64.3
63.2
4 hour
307.0
54.1
8 hour
173.7
42.9
24 hour
63.9
19.8
10 min
157.9
16.0
In ppm
30 min
1 hour
157.9
143.1
15.9
15.6
4 hour
75.7
13.3
8 hour
42.8
10.6
24 hour
15.8
4.9
Page 140

Plots:
Page 141
DERMAL ASSESSMENT INPUTS

Because of limited data for the dermal exposure inputs, differences in the dermal exposure
were only estimated by varying the application method and weight fraction, as shown in
Table D-7.
Table D-7. Dermal Modeling Scenarios.
Case ID
Application Method
Weight Fraction
Central
Brush
2
3
High-end
Central
Spray
High-end
Model Inputs
Table D-8 provides a summary of the parameter inputs for the dermal exposure calculations.
Further discussion of each input follows below.
Table D-8. Summary of Dermal Input Parameters.
Parameter Value
Parameter
Scenario 1:
Brush-on,
Central
Units
Scenario 2:
Brush-on,
High-end
0.25
(median)
Product density
(PD)
g/cm3
1.10 (median)
Brown
(2012)
0.03 (professional judgment)
US EPA
(1996)
cm2
Exposure duration days

(ED)
0.53
(90th
percentile)
Source
Surface area
(SA)
0.44
(median)
Scenario 4:
Spray-on,
High-end
Weight fraction
(WF)
Film thickness (FT) cm
0.50
(90th
percentile)
Scenario 3:
Spray-on,
Central
Brown
(2012)
490 (average); based on 50% of both hands (professional US EPA

judgment)
(2011c)
1 (instantaneous)
Professional
judgment
Frequency of use event/ day 1

(FQ)
Professional
judgment
Body weight (BW) kg
80 (average)
US EPA
(2011c)
Averaging time
(AT)
Professional
judgment
days
Page 142

Weight Fraction
The brush-on and spray-on application methods were assessed using both median weight
fractions (central estimate) and 90th percentile weight fractions (high-end estimate) of paint
stripping products currently available to consumers. The weight fractions used were 0.25 and
0.50 for the brush-on scenarios and 0.44 and 0.53 for the spray-on scenarios, as determined
from Brown (2012). The calculation of these values is discussed above in Inhalation Exposure
Scenario Inputs.
There is a high degree of confidence in the weight fractions used for the paint stripper products
because the values are based on currently available consumer products, as identified in Brown
(2012). However, the weight fractions were not weighted for market share of products.
Product Density
As the range of product densities in NMP-containing paint strippers currently available to
consumers is narrow (0.09 to 1.31 g/cm3), a median product density of 1.10 g/cm3 for all
formulation types was used, as calculated from data in the Brown (2012) spreadsheet.
Similar to the weight fraction parameter, there is a high degree of confidence in the weight
fractions used for the paint stripper products because the values are based on currently
available consumer products, as identified in Brown (2012).
Film Thickness
The film thickness is the amount of material that remains on the skin after contact with the
paint stripper. The data on film thickness are limited, and no data are available specifically for
NMP-based paint strippers. The EFH (US EPA, 2011c) provides film thickness values for a
variety of liquids (mineral oil, cooking oil, bath oil, bath oil/water, water, and water/ethanol),
but not for paint stripper products. Therefore, a generic film thickness value for paint strippers
(0.03 cm) was used based on information provided by Mr. Jordon, a chemist at Klean Strip.
There is a high degree of uncertainty in the film thickness value used because it is based on
professional judgment and there are no details available regarding the derivation of the value.
Additionally, there are questions about the uniformity of films associated with product usage.
Surface Area
There are currently no data on the area of skin exposed to paint stripper products during paint
stripping activities, assuming that protective gloves are not worn. Based on professional
judgment, it is assumed that 50 percent of both hands are exposed to the paint stripper. This
assumption is similar to the previous assumption used in the US EPA (1996) document,
Consumer Exposure Assessment for the Paint Removal Use Cluster, in which it was assumed
that that the palms and fingers of both hands would be exposed to paint strippers (professional
judgment).
Page 143

A value of 490 cm2 was calculated, which is 50 percent of the average surface area of adult
male and female hands, based on average surface areas provided in EFH (1,070 cm2 for males
and 890 cm2 for females). Combined male and female values were not provided in EFH.
There is a high degree of uncertainty with respect to the assumption that 50 percent of both
hands are exposed to the paint stripping product, as no studies have been conducted on this
value. There is a low degree of uncertainty, however, with respect to the surface area values
used for this assumption, as they are recommended values from EFH (US EPA, 2011c), based on
EPA analysis of National Health and Nutrition Examination Survey (NHANES) 2005-2006 data.
Body Weight
A mean body weight of 80 kg was used, as recommended in EFH (US EPA, 2011c) for male and
female adults combined. Both mean body weights and surface areas were used, as combining
surface area distributions with unrelated body weight data may lead to biases in estimating
exposures (Phillips et al., 1993).
There is a low degree of uncertainty with respect to the body weight value used, as it a
recommended value from EFH (US EPA, 2011c), based on EPA analysis of NHANES 1999-2006
data.
Exposure Duration
For acute exposures, an exposure duration of one day was assumed (professional judgment).
This value is typical for the calculation of acute dermal doses. The model assumes that
exposure is instantaneous.
Frequency of Use
For acute exposures, a single exposure event was expected to occur per day (professional
judgment). This value is typical for the calculation of acute dermal doses.
Averaging Time
For acute exposures, an averaging time of one day was assumed (professional judgment). This
value is typical for the calculation of acute dermal doses.
Page 144
Appendix E. Toxicology Studies

INHALATION TOXICITY STUDIES
There were no human health effects studies after exposure to NMP. A summary of the
inhalation animal studies that EPA considered in the analysis follows.
Acute Inhalation Studies. Male and female Wistar rats were exposed head-nose for four hours
to 5,100 mg/m3 of NMP (BASF AG, 1988a; as cited in OECD, 2007). The vapor/aerosol mixture
had a mass median aerodynamic diameter (MMAD) of 4.6 m, and 87 percent of the particles
were in the respirable range. No animals died in the 14-day observation period, and all animals
gained weight.
Male Crl:CD BR rats were head-nose exposed for four hours to 3,100 to 4,800 and 5,000 to
8,800 mg/m3 (E.I. du Pont de Nemours., 1988; as cited in OECD, 2007). At 4,800 mg/m3, four of
six rats died and at 8,800 mg/m3, six of six rats died.
Developmental Toxicity Inhalation Studies. Rats were exposed whole-body to 0, 30, 60, and
120 ppm (122, 243, and 486 mg/m3) for six hrs/day during gestation days (GDs) 6 through 20
(Saillenfait et al., 2001; Saillenfait et al., 2003; as cited in OECD, 2007). There was no difference
in the number of particles in the exposure chamber between control and exposure doses, so
the exposures were to vapor. Slight maternal toxicity was evidenced by significantly decreased
body weight gain in the dams on GDs 6 though 13 at 243 and 486 mg/m3 as well as decreased
food consumption at 486 mg/m3 on GDs 13 through 21. There were no effects on embryo/fetal
viability or teratogenic effects at any dose. There was a slight body weight decrease in the
fetus at 486 mg/m3. The no-observed-adverse-effect level (NOAEL) for maternal toxicity was
122 mg/m3 and the observed fetal NOAEL was 243 mg/m3. EPA performed BMD modeling on
the fetal body weight data (Appendix F; Table F-2). A benchmark concentration level (BMCL)
with a benchmark response of five percent for decreased fetal body weight was used to derive
a BMCL 05 of 302 mg/m3 (US EPA, 2012b).
Rats were exposed to 100 and 360 mg/m3 (analytical) of NMP for six hrs/day from GD 6 through
15 (Lee et al., 1987). Exposures were to aerosol, and the particle size distribution was not
analyzed. However, in a 28-day study in the same laboratory, 95 percent of the particles were
<10 m in diameter. In the dams, sporadic lethargy and irregular respiration were observed
during the first three days of exposure in both dose groups. These signs were not seen during
the remainder of the exposure period or during the 10-day recovery period. These minor signs
of neurotoxicity were reversible and were not considered adverse enough to be used in the
derivation of a point of departure (POD). At 100 mg/m3, there was an increased number of
females with less than 10 corpora lutea compared with controls; this was not treatment related
because NMP exposure began on GD 6. The number of resorptions per litter was lower in this
dose group and the fetal body weight was increased, which could be related to the decreased
Page 145

corpora lutea. There were no treatment-related increases in variations or defects in organs or
skeletal anomalies. The maternal and fetal NOAEL for six hours of exposure was 360 mg/m3.
Hass et al. (1994) investigated the effects of NMP on postnatal development and behavior in
rats. Dams were exposed by whole-body inhalation to analytically determined levels of
151 ppm (612 mg/m3) for six hrs/day from GD 7 to 20. Offspring were weighed through day 22
and males were examined with a series of different behavioral tests from day 1 to 7.5 months.
There were no signs of maternal toxicity, but the mean body weight in litters from exposed
dams was significantly lower than control. The difference in weights was no longer statistically
significant after five weeks of age. Some developmental milestones and reflexes (i.e., surface
righting reflex, incisor eruption, etc.) were delayed in exposed animals. In neurobehavioral
measures (i.e., motor and balance function assessed on rotorod), as well as in activity level (i.e.,
open field) and performance in learning tasks that had a low grade of complexity, there were
no differences between control and exposed animals. However, performance was impaired in
more difficult tasks (i.e., reversal procedure in Morris water maze and operant delayed spatial
alternation). It is interesting to note that the offspring with the lowest score in the Morris
water maze test were those with the lowest body weight at weaning.
Himalayan rabbits were exposed to 0, 200, 500, and 1,000 mg/m3 of NMP for six hrs/day from
GD 7 through 19 (BASF AG, 1991, 1993b; as cited in OECD, 2007). In this study, there was no
maternal toxicity observed. However, a range finding study that assessed a wider range of
parameters showed increased liver weights and impaired clinical chemistry at 1,000 and 2,000
mg/m3. Slight fetal toxicity was observed at 1,000 mg/m3 in the form of increased incidence of
supernumerary rib 13. The NOAEL for maternal toxicity was 1,000 mg/m3 and the NOAEL for
developmental toxicity was 500 mg/m3. OECD (2007) stated that the exposure was to vapor
and vapor-aerosol mixture.
Reproductive Effects Inhalation Studies. Solomon et al. (1995) and E.I. du Pont de Nemours and
Company (1990) exposed rats whole body to 10, 51, and 116 ppm (41, 210, and 470 mg/m3
analytical) for six hrs/day, seven days/week in a 14-week, two-generation reproductive effects
study (as cited in OECD, 2007). There were no effects on reproductive performance. Ovaries
and testes were examined macroscopically, and were weighed and fixed, but no histology was
done. No difference between control and exposed animals in ovary or testis weights was seen.
The only effect seen in the parents was a slight reduced responsiveness to sound at 470 mg/m3.
This effect was minor and the technician performing the test knew which group was the high
dose group. This effect was poorly described in the study. It is unclear how long the effect
persisted. While this will be used to set a NOAEL for the parents, no other signs of narcosis
were observed and this effect was relatively minor (this was considered a mild narcotic effect).
No macroscopic effects or weight changes were seen in testes. However, the testes were not
examined microscopically. The NOAEL for the parents was 210 mg/m3. The only stated effect
for offspring was a slight decrement in fetal and postpartum body weights. In the fetal phase of
the study, there were only control and 470 mg/m3 groups exposed, so only a LOAEL can be
established. However, the Saillenfait et al. (2003) study demonstrated reduced fetal weights at
486 mg/m3, but not at 243 mg/m3. It is likely that 210 mg/m3 would be a NOAEL for fetal body
Page 146

weight change in the Solomon et al. (1995) study. The postpartum data from exposed male and
female animals are difficult to interpret. The low and high doses at days 1, 4, 14, and 21 post
partum showed a statistical difference from the control but the mid-dose did not. The
differences were slight and at the p 0.05 level. Given the lack of a dose response and the
NOAEL for body weight change in the Saillenfait et al. (2003) study, the postpartum weight
differences were not considered significant.
Subchronic Inhalation Studies. Lee et al. (1987) (US EPA, 1989; E.I. Dupont de Nemours & Co.,
1991) exposed rats whole body to design concentrations of 100, 500, and 1,000 mg/m3 of NMP
for six hrs/day, five days/week for 28 days. Some animals were examined after a 14-day
recovery period. Exposure was to a respirable aerosol, with 95 percent of the particles <10 m
in diameter. The measured average calculated NMP concentrations in the test chambers over
the test period were 88, 423, and 740 mg/m3. All rats at all doses exhibited signs of lethargy
and irregular respiration about three to four hours into the exposure through the end of
exposure. Rats recovered within 45 minutes post exposure in the 88 and 423 mg/m3
exposures, but few recovered by 18 hours after exposure in the 740 mg/m3 group. At
740 mg/m3, there were effects on the bone marrow, spleen, lymph tissue in thymus and lymph
nodes, and severe testicular atrophy. However, this was also a lethal level, with eight of 30 rats
dying within nine days and five rats sacrificed in extremis. Dead animals exhibited marked
pulmonary edema and congestion as well as severe systemic effects (bone marrowhemorrhage, hypoplasia, necrosis in hemopoietic cells; lymphoid tissue atrophy and necrosis;
thymus necrosis). These effects were reversible in surviving animals. The only systemic effects
seen at 88 and 423 mg/m3 were slight reversible testicular atrophy in one of 10 male animals in
each dose group (E.I. Dupont de Nemours & Co., 1991) (note Lee et al., 1987 did not mention
the testicular effects ). E.I. Dupont de Nemours & Co. (1991) stated that the testicular results
were tentatively compound related and that this diagnosis would be resolved with the two-year
study. The Lee et al. (1987) report on the two-year study did not indicate any testicular toxicity
at 41 or 405 mg/m3. Since the testicular effects were not repeated, the NOAEL for systemic
effects in the subchronic study is 423 mg/m3. It is interesting to note that the exposures were
vapor in the chronic study and aerosol in the 28-day study to aerosol. The question remains
about the reversible signs of lethargy and irregular respiration at all doses. There was no
mention of such signs in the two-year study (Lee et al., 1987) at doses up to 405 mg/m3. In the
Lee et al. (1987) teratogenicity study at levels of 100 and 360 mg/m3, these signs were seen the
first 3 days of exposure but not after. Since the signs of lethargy and irregular respiration are
reversible and their occurrence differs between experiments, they were not considered adverse
when identifying a NOAEL.
BASF AG (1993a) (as cited in OECD, 2007) conducted a head-nose inhalation study with Wistar
rats. The animals were exposed to 10, 30, and 100 mg/m3 NMP for six hrs/day, five days/week
for 28 days. No treatment-related effects were observed.
BASF AG (1994) exposed Wistar rats head-nose to 500 and 1,000 mg/m3 for six hrs/day, five
days/week for 3 months. A satellite group was exposed to 3,000 mg/m3 for 3 months with a
four-week recovery period. The MMAD was 1.6 to 3.5 m. Nasal irritation was observed at
Page 147

1,000 mg/m3 concentrations. Male rats at 1,000 and 3,000 mg/m3 exhibited a decreased body
weight gain. Male rats at 3,000 mg/m3 exhibited cellular depletion in the testis. Changes in
blood parameters were noted as well as clinical chemistry changes that indicated liver damage,
but the concentration was not specified in the reference. After recovery, the males still
exhibited lower body weight gain and cellular depletion in the testes at 3,000 mg/m3. The
NOAEL for systemic toxicity was 500 mg/m3.
BASF conducted a unique set of experiments on NMP toxicity and the character of the
inhalation experience (BASF AG, 1995c, 1989, 1995b, a, 1992; as cited in OECD, 2007). SpragueDawley or Wistar rats were exposed whole body or head-nose to 1,000 mg/m3 for six hrs/day,
five days/week for two or four weeks. Exposure to NMP was to coarse and fine particles of
NMP in a vapor aerosol mixture. Regardless of particle size, the head-nose exposure caused
only slight nasal irritation. However, rats exposed whole body to coarse droplets and high
humidity experienced massive mortality and severe effects on organs and tissues, as well as
other effects. Whole-body exposures to fine droplets under high or low humidity conditions
did not result in mortality, and effects seen were less severe than with the coarse droplets.
Chronic Inhalation Studies. DuPont conducted a two-year cancer bioassay in rats (E.I. Dupont
de Nemours & Co., 1990; Lee et al., 1987; WHO, 1986; Kennedy, 2008; as cited in OECD, 2007).
Rats were exposed whole body to 10 and 100 ppm (41 and 405 mg/m3) for six hrs/day, five
days/week for two years. Exposure was to vapor; only a trace amount of aerosol was detected.
The design concentrations were 10 and 100 ppm, and the means of the high- and lowexposure weekly time-weighted average concentrations were 99.3% and 97.4% of design,
respectively, over the duration of the study (E.I. Dupont de Nemours & Co., 1990). The
duration of the study was 24 months with interim sacrifices at 3, 12, and 18 months. There
were no signs of intoxication. Males at 405 mg/m3 exhibited a six percent body weight loss. At
the 405 mg/m3 exposure, male rats exhibited higher-than-normal hematocrit, alkaline
phosphatase, and urine volumes. Exposed rat urine was darker than control. No treatmentrelated tumors were found, and the hematology, clinical chemistry, urinalysis, gross pathology,
and histopathology did not exhibit treatment-related changes other than noted above. The
effects seen at 405 mg/m3 are minimal and not biologically significant. The NOAEL for this
study was 405 mg/m3.
DERMAL TOXICITY STUDIES

There were no human health effects studies identified for dermal exposure to NMP. A
summary of the available dermal animal studies that EPA considered is provided below.
Acute Dermal Toxicity Studies. Male and female Sprague-Dawley rats (two per sex) were
exposed dermally for 24 hours to 5,000 mg/kg of NMP (Clark et al., 1984; as cited in OECD,
2007). No rats died, and there was no mention of any gross pathology changes.
Page 148

Female Wistar rats (number not specified) were exposed dermally to 5,000 and 10,000 mg/kg
for 24 hours (Weisbrod, 1981; Weisbrod and Seyring, 1980; as cited in OECD, 2007). No rats
died at 5,000 mg/kg, and all rats died at 10,000 mg/kg.
Developmental Toxicity of Dermal Exposures. Rats were exposed dermally for eight hours to 75,
237, and 750 mg/kg from GD 6 through 15. Dams had collars to prevent oral ingestion (Becci et
al., 1981; Becci et al., 1982; FDRL, 1979; E.I. Dupont de Nemours & Co., 1992; as cited in OECD,
2007). Patches of dry skin were noted in a dose-dependent manner at the application site at all
doses in the dams. The dams experienced a 17 percent (incorrectly cited as 28 percent in
OECD, 2007) reduction in body weight gain at 750 mg/kg, but not at the lower doses.
Developmental toxicity expressed as fewer live fetuses, increased resorption rate, reduced fetal
body weight, and several skeletal abnormalities only at the high dose. It was not determined
whether the fetal toxicity was due to maternal toxicity or directly to the compound. The NOAEL
for maternal and developmental toxicity was 237 mg/kg. An important note comes from the
results of a range-finding study conducted by the same authors. In this study, all dams from a
2,500 mg/kg exposure group died before GD 20. In the 1,100 mg/kg exposure group, 65 of
66 fetuses were resorbed. The NOAEL of 237 mg/kg is essentially within a factor of 4+ of a
totally lethal outcome for the fetus.
Rabbits were exposed dermaly for six hrs/day to 100, 300, and 1,000 mg/kg from days seven
through 19 of pregnancy (BASF AG, 1993b). There were no toxic effects expressed in the dams.
The only sign of fetal toxicity was a small increase in supernumerary 13th ribs at the high dose, a
common variation in Himalayan rabbits. The NOAEL for maternal toxicity in this experiment
was 1,000 mg/kg, and the NOAEL for fetal toxicity was 300 mg/kg.
Subchronic Dermal Toxicity Studies. Albino rabbits were exposed to 413, 826, and 1,653 mg/kg
on intact or abraded skin for five days/week over four weeks (GAF Corp., 1986; Industrial
Biology Research and Testing Laboratories., 1963; as cited in OECD, 2007). Mild irritation was
noted at all doses. Other than one death in a 1,653 mg/kg treated rabbit in the abraded skin
group, no systemic toxicity to clinical, hematological, or histopathological measures were seen.
The NOAEL for systemic toxicity was 826 mg/kg.
IRRITATION, SENSITIZATION, AND CANCER

NMP is a mild skin and eye irritant in rabbits. In animal studies, exposure to aerosols leads to
upper respiratory irritation. In humans, NMP is not irritating to the eyes or upper respiratory
tract, but is a skin irritant. Information from secondary literature sources suggests that NMP is
not a skin sensitizer in animals or humans (OECD, 2007). NMP is considered non-carcinogenic,
and most mutagenicity studies have been negative.
Page 149
Appendix F. BMD Analysis of Saillenfait et al. (2003) Data

BMD Analysis
Dose-response modeling was performed using the EPAs Benchmark Dose Software (BMDS,
v.2.1.1.) in accordance with the Benchmark Dose Technical Guidance Document (U.S. EPA,
2012). All standard continuous-variable models were fit to the selected continuous dataset
shown in Table F-1. Since developmental studies with nested study designs often have greater
sensitivity, and the effect being modeled is a developmental effect a BMR of 5% relative
deviation was used (US EPA, 2012b).
Inhalation Data
The mean fetal body weight data shown in Table F-1 were assessed against the maternal NMP
levels.
Table F-1. Fetal body weight data from pregnant Sprague-Dawley rats exposed to NMP from GD 620.a
Dose
mg/m3 (ppm)
Number
(all fetuses)
Fetal body weight (g)

Mean Standard Deviation
0 (0)
24
5.671 0.370
122 (30)
20
5.623 0.358
243 (60)
19
5.469 0.252
487 (120)
25
5.393 0.446
Raw data obtained directly from the study authors; summary data were provided in Table 2 of Saillenfait et al.
(2003)
BMD Modeling Results

BMD modeling resulted in the estimation of the POD for fetal/pup body weight changes
observed in rats without accounting for litter effects. The BMCL 05 is defined as the lower 95
percent confidence limit of the five percent decrement in fetal body weight. A list of the
resulting BMCs and BMCL 05 s are shown in Table F-2. Adequate model fits were achieved for
the dataset with Exponential Model 2 (Figure F-1) and Exponential Model 3 (Figure F-2).
weight from pregnant Sprague-Dawley rats exposed to NMP from GD 6-20.
BMCL
mg/m3 (ppm)
(BMR = 5% Relative
Deviation)
AIC
BMC
mg/m3 (ppm)
(BMR = 5% Relative
Deviation)
Hill
-81.07
612.42 (151.05)
130.19 (32.11)
Linear
-84.49
476.96 (117.64)
307.53 (75.85)
Modela,b
Page 150

weight from pregnant Sprague-Dawley rats exposed to NMP from GD 6-20.
BMCL
mg/m3 (ppm)
(BMR = 5% Relative
Deviation)
AIC
BMC
mg/m3 (ppm)
(BMR = 5% Relative
Deviation)
Polynomial (second order)
-84.49
476.96 (117.64)
307.53 (75.85)
Power
Exponential Model 2
-84.49
-84.51
476.96 (117.64)
475.34 (117.24)
307.53 (75.85)
301.97 (74.48)
Exponential Model 3
-84.51
475.34 (117.24)
301.97 (74.48)
Exponential Model 4
-82.63
460.58 (113.60)
173.41 (42.77)
Modela,b
BMD model runs were performed on the data from Table D-1 using EPAs Benchmark Dose Software (BMDS)
Version 2.1.
b
The models with the lowest AIC values are shown in bold; the plots of these values are shown in Figures F-1
and F-2.
Page 151
Exponential Model 2 with 0.95 Confidence Level

Exponential
5.8
Mean Response
5.7
5.6
5.5
5.4
5.3
5.2
BMDL
0
17:14 09/06 2012
20
40
60
80
dose
BMD
100
120
140
Exponential model 2.
Page 152

Exponential Model 3 with 0.95 Confidence Level
Exponential
5.8
Mean Response
5.7
5.6
5.5
5.4
5.3
5.2
BMDL
0
17:14 09/06 2012
20
40
60
80
dose
BMD
100
120
140
Exponential model 3.
Page 153
Appendix G. EPAs Evaluation of the Poet et al. (2012) PBPK

Model for NMP
Summary
EPA's review of the PBPK model (Poet et al., 2010) found that a number of the results shown in
the published model and its figures are not reproducible using (preferentially) the model
parameters listed in that publication (model parameters not listed in the publication were
taken from model files supplied by the authors). While the model structure, including its
description of physiological changes during pregnancy, appears to be mostly appropriate, there
is significant unresolved uncertainty as to which fitted (chemical-specific) parameters were
actually used to obtain the fits shown by Poet et al. (2010). Therefore, if there is a single,
consistent set of parameters that adequately describes the pharmacokinetic data for rats and
humans, it is not transparent. Resolution of these issues may simply require replacing
parameter values listed in the publication with those found in model code files. Alternately, recalibration of the rat and human models may be necessary.
EPAs Evaluation of the Poet el al. (2010) PBPK Model
This appendix describes the EPAs attempt to reproduce and thereby partially test the PBPK
model of Poet et al. (2012) for NMP disposition in rats and humans. The model was
implemented in acslX v. 3.0.2.1 (The AEgis Technologies Group, Inc., Huntsville, AL). The
containing acslX workspace has two projects, one for the rat PBPK model and one for the
human PBPK model. Both are based upon model files received from the authors, with relatively
minor substantial modification, though a number of comments have been added.
For both rats and humans the pregnancy versions of the model were used, and a switch
was added, where when the parameter PREG is set to zero, the time-dependent changes that
occur during pregnancy are turned off, hence the model represents a non-pregnant adult
female as being identical to the physiological state at the immediate inception of pregnancy.
This was done to simplify the model evaluation process, and with the assumption that the
physiological differences between an adult male and an adult non-pregnant female will have a
negligible effect on model predictions. The non-pregnant versions of the model code received
do not have any gender-specific tissues, such as a uterus or mammary gland. The volume of the
uterus is relatively small in non-pregnant females and mammary tissue would otherwise be
lumped into the slowly perfused or fat compartments of both males and females, and neither
of these are metabolizing tissues. Therefore, pregnancy-day-zero model predictions are
reasonably expected to be essentially identical to male/gender-non-specific model simulations,
provided that the chemical-specific parameters are otherwise identical and appropriate values
for the physiological parameters are used.
Below, results of simulations with the models in this workspace are shown and described.
Page 154

Rat NMP workspace / model results
Besides the specific Runtime (.m) files listed below, the workspace contains rat_params.m,
which sets the parameters (called by other files), two half vmax files used to test the
sensitivity to that parameter, and ghantinhaldata.m which defines the data set for Figure 4.
The first figure below attempts to reproduce Figure 2A of Poet et al. (2012), and is created
using Poet 2012 Fig 2a.m in the workspace. The curves are simulations obtained by EPA with
the model. The points were obtained from the published figure using digitization software.
While most of the published curves were reproduced well, the changes in fetal weight are a bit
off and the total body weight (BW) diverges considerably after day 10. Neither the paper nor
the code files received specified the number of fetuses used, but a value of 11 was found to
provide an exact match for the fetal volume (weight) and the best possible match for the (total)
fetus volume (weight).
The next plot, produced by Poet 2012 Figure 3A.m compares current simulations with
published results in Figure 3A. The large points are the data shown in the figure, while the
small points were digitally extracted from the published figure. The current simulation (solid
line) matches almost exactly the published results.
Page 155
The next two figures, produced by Poet Fig4 2012.m, compare current simulations with
published results in Figure 4. Figure 4A (first plot) only showed the upper set of male-rat data,
and the heavy dark line as a prediction. The current simulations for males and females
were obtained by setting gender-specific body weights to those set correspondingly in the
model code files received, for these specific data sets. Both sets of current simulations fail to
match the published result to a degree that is numerically significant (more than should be
expected from using a newer software platform) and the female data (not shown in the
published figure) are over-predicted almost two-fold.
Page 156
The following table compares results obtained with files Saillenfait 2003 rat.m and Solomon
1995 rat.m to those in Tables 3 and 4, respectively, of Poet et al. (2012).
Page 157
Table G-1. Comparison of average daily plasma NMP AUCs from Poet et al. 2012 (Tables 3 and 4) and
present (10/16/12) simulations of rat inhalation repro/developmental bioassays, using study-specific
body weights.
Saillenfait et al. (2003) / Poet et al. Table 3
External
Concentration
(ppm)
30
60
120
Published
Average
Daily
Plasma
NMP AUC
(mg*hr/L)
94.6
193
403
Solomon et al. (1995) / Poet et al. Table 4
Present
Average
Daily Plasma
NMP AUC
(mg*hr/L)
%
difference
External
Conc.
(ppm)
95.9
195.8
407.5
1.0
1.0
1.0
10.3
50.8
116
Published
Average
Daily
Plasma
NMP AUC
(mg*hr/L)
31.8
162
387
Present
Average
Daily Plasma
NMP AUC
(mg*hr/L)
%
difference
32.2
163
387
1.3
0.6
0.0
Human NMP workspace / model results

Besides the results shown below, the workspace includes Preg vs nonpreg AUCs.m which
shows how the AUC metric changes during pregnancy and Table 7 HECs with half Vmax.m
that allows for a comparison with that change in the Vmax.
Poet 2012 Fig 2B human.m and Poet 2012 Fig 2C human.m show an effectively identical
match between the current simulations and published results (next 3 plots).
Page 158
The next set of plots are attempts to reproduce the panels of Figure 6, produced by Poet 2012
Fig 6 human.m. As the model files received included the data for individual subjects from the
study conducted by Poet et al., those data are shown rather than the single points (assumed to
be averages) shown in the published figure. In the first four plots below (panels A-D) the thin,
dotted lines are digitized from the published figure, and the heavy solid lines are current model
predictions. It is seen that the current simulations differ significantly from those shown in the
publication. While the results for NMP, Figure 6A and 6C, are within the range of variability
shown by the data, the results for the metabolite 5-HNMP significantly under-predict the data
(and published simulations).
Page 159
Page 160
The next plot, Figure 6E, shows current model simulations vs. the data. In this case the model
reproduces the published simulations (not shown) quite well.
Page 161
However, in Figure 6F the simulated results (curves shown) under-predict the published
simulations at short times (results not shown) and over-predicts those results at later times.
The next two figures, produced by Poet 2012 Fig 7 human.m, attempt to reproduce the
panels for subject A and Observers. The simulated results (curves shown) substantially underpredict the data (points) and simulations shown in the published figure (results not shown).
Page 162
The next table compares results from Poet et al. Table 7 to those produced by Poet 2012 Table
7 HECs.m. The current simulations yield HECs that are 11-21% higher than published.
Page 163
Table G-2. Comparison of rat internal dose BMC values and HECs from Poet et al. (2012) and present
simulations
Simulations
Rat Data Set
Poet et al. (2012)

Table 7
Saillenfait et al. 2003

Solomon et al. 2003
Saillenfait et al. 2003
Present
Solomon et al. 2003
Internal Dose
(avg daily NMP AUC,
mg*hr/L)
BMC1SD
BMCL1SD
470
340
540
360
470
340
540
360
HEC in ppm
(8hrs/day, 5 days/week,
9 months)
BMC1SD
BMCL1SD
650
470
750
500
745
569
832
597
PBPK model uncertainty, BMD and PBPK extrapolation for inhalation POD.
The rat PBPK model established the relationship between NMP concentrations in maternal
blood and reductions in fetal/pup BWs following exposure to NMP vapor. This relationship is
based on the assumption that maternal dose is proportional to fetal dose (Poet et al., 2010).
Direct evidence is not available for this assumption, which is a key uncertainty of this modeling
study.
One of the most sensitive toxicological endpoint associated with exposure (oral, dermal, and
inhalation) to NMP is fetal/pup body weight deficits resulting from maternal exposures. In an
effort to reduce uncertainty associated with extrapolating findings from animal toxicity studies
to humans, a PBPK model was developed by Poet et al. (2010) initially for adult non-pregnant
rats and then extrapolated to pregnancy. Although the model represents a good effort towards
reducing uncertainty due to extrapolation, it falls short at this time for quantitative use in
deriving a point of departure for risk assessment.
EPA's initial review of the PBPK model (Poet et al., 2010) has found that a number of the results
shown in the published model figures are not reproducible using (preferentially) the model
parameters listed in that publication (Model parameters not listed in the publication were
taken from model files supplied by the authors). The model structure, including its description
of physiological changes during pregnancy, appears to be mostly appropriate. However, there
is uncertainty as to which fitted (chemical-specific) parameters were actually used to obtain the
fits shown by Poet et al. (2010), and hence if there is a single, consistent set of parameters
which adequately describe the pharmacokinetic (PK) data for rats and humans. Resolution of
these issues may simply require replacing parameter values listed in the publication with those
found in model code files. Alternately, re-calibration of the rat and human models may be
necessary.
Another issue of significant concern is that the rat PBPK model was calibrated using nose-only
inhalation exposure (pharmacokinetic) data, and hence with skin absorption set to a near-zero
value. However the bioassays from which dose-response data are available used whole-body
exposures, for which skin absorption is expected to be significant. Therefore skin absorption
Page 164

should be enabled when simulating bioassay conditions, and this component of the rat model
has not been calibrated or tested against any PK data.
Another uncertainty is that the metabolic parameters obtained by calibration against PK data
from non-pregnant adults are assumed to remain unchanged during pregnancy. There are no
PK data for NMP during pregnancy to test this assumption, but rates of metabolism of some
other substances are known to change substantially during pregnancy. It should be noted,
though, that such an assumption is effectively implicit in default risk-extrapolation methods
which do not make use of PBPK models. Identification of the specific enzymes involved in NMP
metabolism and any data on their changes during pregnancy could address this uncertainty.
An acute POD can be derived from the PBPK modeling of the Saillenfait et al. data (Poet et al.,
2010). The modeled HEC was 1,905 mg/m3 for an 8-hour exposure. Poet et al. (2010) used rat
and human PBPK models in combination with Benchmark Dose (BMD) analysis to predict the
HEC from rat exposure data to better inform dose-response calculations. The model estimated
adult blood concentrations of NMP in the rat and used BMD analysis on the modeled results to
determine a HEC.
The toxicity of NMP is greatest from exposure to the parent compound. NMP had the most
embryotoxic effect in whole-embryo culture (Flick et al., 2009 as cited in Poet et al., 2010) and
in in vivo developmental toxicity studies (Saillenfait et al., 2007 as cited in Poet et al., 2010).
NMPs major metabolite is 5-hydroxy-N-methyl-2-pyrrolidone (5-HNMP) which can be further
metabolized into N-methylsuccinimide (MSI) and 2-hydrooxy-N-methyl succinimide (2-HMSI).
In the PBPK modeling, blood AUC levels of both NMP and 5-HNMP were modeled but the NMP
concentrations were used to estimate the HEC. Maternal blood concentrations of NMP were
well predicted in rats and humans. NMP levels were proportionally higher than 5-HNMP in rats
because humans metabolize NMP at a higher rate. Maternal blood concentrations of NMP
were used as the metric because the lack of fetal validation data made the fetal internal dose
measures too uncertain. This was considered to be a conservative approach because the
modeled human fetal concentrations are relatively lower than the rat (Poet et al., 2010).
Two inhalation studies were modeled: Saillenfait et al. (2003) and Solomon et al. (1995) with
Staples (1990; as cited in Poet et al., 2010). These studies are described in the Hazard
Identification section. The Haskells inhalation rat reproductive and developmental studies
were reported in Solomon et al. (1995) and E.I. du Pont de Nemours and Company (1990) (the
latter also called Staples 1990 in Poet et al., 2010 and in the PBPK descriptions below).
Saillenfait et al. (2003) reported a reduced fetal body weight (BW) NOAEL and LOAEL of 243
mg/m3 (60 ppm) and 486 mg/m3 (120 ppm), respectively. A NOAEL of 210 mg/m3 was
reported for pup body weight decrease in Solomon et al. 1995 and E.I. du Pont de Nemours
and Company, 1990/Staples, 1990.
Mean fetal BWs were assessed against the modeled maternal NMP levels using the US EPA
Benchmark Dose Software (BMDS, version 2.1). BMD modeling resulted in the estimation of
the POD for fetal/pub BW changes observed in rats without accounting for litter effects. A
nested model for continuous datasets was not available to the authors when conducting the
Page 165

PBPK modeling. They also argued that the mild and reversible maternal effects rendered
support to not using the nested model in the analysis (Poet et al., 2010).
The fetal/pub POD and the human PBPK model are used to estimate the HEC corresponding to
the lower 95% confidence limit of the 8-hr benchmark concentration for 1 standard deviation
(or 8-hr BMCL 1SD ). This estimate is considered a NOAEL for the human health risk assessment.
From Saillenfait et al. (2003), the HEC corresponding to the 8-hr BMCL 1SD was 1,905 mg/m3 (470
ppm). For the Solomon et al. (1995)/Staples (1990) data (as cited in Poet et al., 2010), the HEC
corresponding to the BMCL 1SD was 2,027 mg/m3 (500 ppm). Because the HEC BMCL1SD values are
very similar (i.e., 1,905 versus 2,027 mg/m3), this analysis uses the 8-hr HEC BMCL1SD value (1,905
mg/m3) from Saillenfait et al. (2003) to alternatively assess the acute inhalation risks for
residential users and non-users.
Time scaling is required for both acute PODs [i.e., 6-hr HEC of 302 mg/m3 (BMD analysis) and 8hr HEC BMCL1SD of 1,905 mg/m3 (PBPK modeling)]. This is because the acute PODs correspond to
6- or 8-hr exposures, but the human exposure estimates are presented as peak TWAs for 1, 10,
and 30 minutes and 1, 4, 8 and 24 hours. Most users would be applying NMP-containing paint
strippers for about a period of 4-hrs. We chose to time scale the acute PODs to 4 hrs.
Assuming Habers Rule (C x t=k), the scaled acute PODs (4-hr) are the following: (1) 453 mg/m3
(based on the BMD analysis) and (2) 3,810 mg/m3 (based on the PBPK modeling). The PBPK
modeling is increasing the acute POD by approximately 10-fold when compared to the default
approach (i.e., BMD analysis with no modeling).
On the other hand, the alternative acute POD (3,810 mg/m3) was derived with PBPK modeling,
which reduced the pharmacokinetic uncertainties of extrapolating from animals to humans. In
this case, the interspecies component is reduced from 10 to 3. The default intraspecies UF of
10 is retained because of insufficient data to support a reduction. The total uncertainty (or
level of concern) captured in the MOE approach for the PBPK-derived POD is 30.
Page 166

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