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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

Th is assessment focus ed 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, productio n, 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 provide s a clear and logical summary of EPA’s analysis

. P lease provide specific suggestions for improving the

document.

Question 1

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

and accura tely 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 l imited 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.Page 2 of 4 Question 3

- 2 : Please comment on the assumptions that EPA used to estimate film thickness ( e.g,. Specifically on the size of area exposed a nd 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 non

user ( 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 consume r 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 o r 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 concentrat ions.

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 th e 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 woul d 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.Page 3 of 4 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? P lease provide data or documentation and rationale for including other studies and endpoints for these scenarios.

Pl ease 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 expo s ure. Please specify any other endpoints that could be considered for

the hazard of acute inhalatio n 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 t h e 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? P lease provide data or documentation and rationale for including other studies and endpoints to be considered. Please comment on the strengths and wea knesses of approaches used to estimate inhalation exposure responses used for margins of exposure.

Issue 10 . Poet et al . (2010) modeled the b ody w eight 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) model 1 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 A ppendix

G ). If these uncertainties were resolved, t he 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.htmlPage 4 of 4 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 inte r nal 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

.