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OPPT Proposed Draft Charge to External Peer Reviewers for the review of 

the TSCA Workplan Chemical Risk Assessment of NMP

December 2012

This assessment focused on the use-application of NMP in paint stripping products. For this use, 

chronic dermal and inhalation exposures were assessed for workers; acute dermal and inhalation 

exposures were assessed for consumers; and acute inhalation exposures were assessed for 

bystanders. 

General question on the risk assessment

Issue 1. General Question on the Risk Assessment of NMP

The document describes the scope for the NMP human health risk assessment (Chapter 1); 

provides information on chemistry, environmental fate and transport, production, and uses 

(Chapter 2); and characterizes exposure, hazard, and risk (Chapter 3). Supporting information is 

provided in the appendices. The risk assessment is intended to provide a clear and transparent 

summary of EPA’s analysis.

Question 1-1: Please comment on whether the assessment provides a clear and logical

summary of EPA’s analysis. Please provide specific suggestions for improving the 

document. 

Question 1-2: Please comment on whether appropriate background information is provided 

and accurately characterized. Please provide any other significant literature, reports, or data 

that would be useful to complete this assessment. 

Questions for the assessment of occupational exposure of NMP

Issue 2. EPA focused this assessment on occupational exposures in small commercial shop 

settings. EPA found limited published data for NMP air concentrations in small 

commercial shop workplace settings during use of NMP-based paint strippers. These data 

were used to estimate occupational inhalation exposures.

Question 2-1: What other sources of data are available for estimating occupational 

inhalation exposures during use of NMP-based paint strippers? Please specify what other 

sources are available to estimate these occupational inhalation exposures. 

Issue 3. No data were found for occupational dermal exposures for the use of NMP-based 

paint strippers. The occupational exposure assessment used an EPA model to estimate 

dermal exposures to liquid NMP-based paint stripper.

Question 3-1: Please specify other data that could be used to estimate occupational dermal

exposures during use of NMP-based paint strippers. Please specify sources of these data.
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Question 3-2: Please comment on the assumptions that EPA used to estimate film thickness

(e.g,. Specifically on the size of area exposed and the duration of exposures) and number of 

events per day to estimate occupational dermal exposures.

Questions for the assessment of consumer exposure of NMP

Issue 4. EPA conducted a literature review to identify consumer user and residential nonuser (i.e., bystanders not in the immediate area of the activity) exposures from inhalation 

and dermal routes. Insufficient data were found to assess these exposures. Therefore, EPA 

used models to estimate inhalation and dermal exposures. The estimation of consumer uses 

and profiles is based upon limited data.

Question 4-1: Are there other sources of data or information that could be used to assess 

consumer user and residential non-user exposures? Please specify sources of these data.

Question 4-2: Are there additional data or other emission profiles for NMP application that 

could be used to support EPA’s modeling approach? Please specify sources of these data.

Please comment on the strengths and weaknesses of the modeling approach used to estimate 

exposures.

Issue 5. EPA conducted a sensitivity analysis of model parameters to identify critical 

parameters essential to the modeling approach used to estimate inhalation exposures. EPA 

varied the most sensitive input parameters to generate upper end concentrations.

Question 5-1: Is the panel aware of additional data that would support EPA’s modeling 

approach to estimate consumer inhalation exposures? Please comment on the type of 

sensitivity analysis conducted for the assessment. Please provide suggestions and references 

to support any alternate approaches proposed. 

Issue 6. EPA did not find published data for estimating consumer user dermal exposures 

for the use of NMP paint strippers. The consumer exposure assessment used an EPA 

model (E-FAST2/CEM) to estimate dermal exposures to liquid NMP.

Question 6-1: What additional sources of data is the panel aware of that would provide an 

estimate of consumer user dermal exposure? Please specify sources of these data.

Question 6-2: Please comment on the assumptions EPA used for the film thickness and 

number of events per day. Please comment on the strengths and weaknesses of the modeling 

approach used to estimate dermal exposures.

Questions for the assessment of human health and of risks to NMP

Issue 7. Based on its review of published studies, EPA chose a developmental dermal study 

in rats to characterize acute and chronic hazard for the dermal exposure scenario. From 

this developmental study, EPA chose a decrement in fetal body weight and fetal death as 

key outcome to represent the effects of single acute and chronic dermal exposure.
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Question 7-1: Please comment on the approach used and specify what other endpoints could 

be considered for hazard of acute and chronic dermal exposures? Please provide data or 

documentation and rationale for including other studies and endpoints for these scenarios.

Please comment on the strengths and weaknesses of approaches used to estimate dermal 

exposure responses and margins of exposure.

Issue 8. Based on the results of its extensive literature search and evaluation, EPA chose a 

developmental inhalation study in rats for the acute inhalation duration scenario. From 

this developmental study, EPA chose a decrement in fetal body weight as the key outcome 

to represent the effects of single acute inhalation exposure.

Question 8-1: Please comment on EPA’s use of this study and approach in assessing acute 

inhalation exposures, the use of the developmental toxicity endpoint, and the identified 

effects of a single exposure. Please specify any other endpoints that could be considered for 

the hazard of acute inhalation exposures? If so, please provide data or documentation and 

rationale for including other studies and endpoints to be considered. 

Issue 9. For chronic inhalation exposure scenarios, EPA also chose to use developmental 

inhalation studies in rats for the inhalation duration scenario. From this developmental 

study, EPA chose a decrement in fetal body weight and maternal toxicity as well as a 

NOEAL in chronic 2 year rat inhalation study. These multiple studies and endpoints were 

selected to represent the hazards to a range of populations who might experience chronic 

inhalation exposures. 

Question 9-1: Please comment on EPA’s approach for determining chronic inhalation 

exposures, the use of the developmental toxicity endpoint, and the identified effects. Please 

specify any other endpoints that could be considered for hazard of chronic inhalation 

exposures? Please provide data or documentation and rationale for including other studies 

and endpoints to be considered. Please comment on the strengths and weaknesses of 

approaches used to estimate inhalation exposure responses used for margins of exposure.

Issue 10. Poet et al. (2010) modeled the body weight decrease in fetuses from the Saillenfait 

et al. (2003) study using physiologically based pharmacokinetic modeling (PBPK) and 

benchmark dose (BMD) methodologies. EPA evaluated the Poet et al. (2010) model1 and 

determined that it was not suitable for this assessment because of questions about the 

documentation, accuracy of the model, and its use to predict risk (described in Appendix 

G). If these uncertainties were resolved, the output of this model could be used as an 

alternative to the classic approach described in the risk characterization section.

 1 The model titled “NMP PBPK Model.zip” is available at 

http://www.epa.gov/oppt/existingchemicals/pubs/workplans.html
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Question 10-1: Please review the model and EPA evaluation of Poet et al. (2010). Please 

comment on the strengths and weaknesses of the modeling approaches used to estimate internal 

dose metrics for inhalation exposures. Please comment on the strengths and weaknesses of the 

modeling approach for extrapolation of rat to human equivalent concentrations (i.e., species to 

species extrapolations) for risk estimation for developmental effects.