ROHACH,hr‐110Openwindows/1.260.45Coffeetable(Professionaljudgment,90thpercentile)(central)(central)0.5(upper‐end)Upper‐endfor250.18non‐userChestofdrawers(low‐end)(upper‐end)0.5 369cWindowclosed,noexhaustfan/0.18d0.18(upper‐end) Bathtub (low‐end)(low‐end) (low‐end)(maximum)Brush‐onExposureScenariosinWorkshopBrush‐onExposureScenarioinBathroomROH(entiretime)WorkshopChest:12.5/30/25min.perapplication;processrepeatedaftercompletionoffirstscraping.Scrapingsremovedfromhouseafterlastscraping.ROH4and5Upper‐endtoboundingforuserandnon‐user108 0.8695Bathtub:18‐min.application,30‐min.waitand36‐min.scrapeperapplication;processrepeatedaftercompletionoffirstscraping.Scrapingsremovedfromhouseafterlastscraping.492(central) ROH31 Central0.25(central)108 0.8695Coffeetable:5‐min.application,30‐min.waitand10‐min.scrapeperapplication;processrepeatedaftercompletionoffirstscraping.Scrapingsremovedfromhouseafterlastscraping.54(central) 492(central)ROHROH(entiretime)2Upper‐endforuserUserLocationDuringWaitPeriodbNon‐UserLocationWeightFractionSurfaceAreaTreated,aft2ApplicationRate,g/ft2ReleaseFractionVolume,m3Ventilation/ACH,1/hrVolume,m3HouseCaseID ScenarioNMPReleasedStrippingMethodRoomofUseROHACH,hr‐1UserLocationDuringWaitPeriodbNon‐UserLocationWeightFractionSurfaceAreaTreated,aft2ApplicationRate,g/ft2ReleaseFractionVolume,m3Ventilation/ACH,1/hrVolume,m3HouseCaseID ScenarioNMPReleasedStrippingMethodRoomofUseUpper‐endforuser0.53 10Openwindows/1.260.45(Lowersprayvolatility)e(upper‐end) Coffeetable(Professionaljudgment,90thpercentile)(central)Upper‐endforuser(central)(Uppersprayvolatility)eUpper‐endfor0.53 250.18non‐user (upper‐end)Chestofdrawers(low‐end)(Lowersprayvolatility)e(upper‐end)Upper‐endfornon‐user(Uppersprayvolatility)edBecausetheuserisworkingincloseproximitytothetarget(bathtub)foranextendedperiod,athirdzone(“sourcecloud”)wascreatedwithinthebathroomtorepresenttheNMPconcentrationsinthevicinityofthetub;thisisavirtualzone,withnophysicalboundaries.TheairflowratebetweenthecloudandtherestofthebathroomwasbasedonworkbyMatthewsetal.(1989).(Formoreinformation,seediscussioninAppendixEunderInhalationExposureScenarioInputs(AirflowRatesandVolumes.)eForthefirstexponential,theUpperspraycaseassigns10timesthemassoftheLowerspraycase.Thetheoreticaltotalmassreleasedisthesameforthetwocases.SeeEstimationProceduresforSprayApplicationinSectionE‐1ofAppendixEforadetaileddescription.Spray‐onExposureScenariosinWorkshopaThesurfaceareavalueswereselectedsothatthecalculatedamountofproductapplied(g)correspondsapproximatelytotheAbt(1992)surveyresultsforamountofpaintstripperused(50thpercentilebForallscenarios,theuserisinthetreatmentroomduringtheapplicationandscrapingtimesandintheROHafterthelastscraping.c1m3forthevicinityofthetub(sourcecloud)and8m3fortherestofthebathroom.dBecausetheuserisworkingincloseproximitytothetarget(bathtub)foranextendedperiod,athirdzone(“sourcecloud”)wascreatedwithinthebathroomtorepresenttheNMPconcentrationsintheWorkshopROH(entiretime)6b7aChest:6.25/30/25min.perapplication;processrepeatedaftercompletionoffirstscraping.Scrapingsremovedfromhouseafterlastscraping.ROH7b6a81 0.8695Coffeetable:2.5‐min.application,30‐min.waitand10‐min.scrapeperapplication;processrepeatedaftercompletionoffirstscraping.Scrapingsremovedfromhouseafterlastscraping.54(central) 492(central)

# Page 1



# NMP Residential Scenarios

Assumptions:

Consumers and residential non-users exposed to NMP-based paint strippers based on the scenarios descriptions in Tab#1 (Table 2-5 of NMP risk assessment)

→→ Dermal exposure to the NMP vapor is assumed to be on 4989 cm2 of skin (25% of the total surface area of an average woman) when the user is not applying or in contact with the product.

During spray application 1 cm2 is assumed to be wetted by liquid and the same areas are exposed to vapor as during brush application

Maternal blood AUC or Cmax of parent compound used as a surrogate for fetal dose metric

Preferred dose metrics:

Acute risks were assumed to occur in consumer users and bystanders, but not chronic risks and thus only acute risks were evaluated

The endpoints of fetal skeletal malformations, resorptions and fetal mortality are biologically relevant to actue exposures

Cmax (mg/L) is preferred for acute effects assuming that a single dose effect is need to induce these effects

Preferred benchmark MOE:

Margin of Exposures (MOEs) were compared to a benchmark MOE of 30 to determine whether risks were present for the different exposure scenarios.

The benchmark MOE of 30 consists of

3X was used for interspecies variability. The PBPK model was used for interspecies extrapolation.

10X was used to account for human variability. The PBPK model did not account for human toxicokinetic variability. The data used in the human PBPK model was based on healthy humans.

In addition, CYP2E1 is partly involved in the metabolism of NMP in humans. There are large variations in CYP2E1 activity in humans (Ligocka et al., 2003) which supported the retention of the 10X.

See Ligocka et al., 2003 at http://www.ncbi.nlm.nih.gov/pubmed/12734639. Dermal exposures to the liquid NMP product are assumed to be on 490 cm 2 of skin for users without gloves.

All of the exposure scenarios assumed vapor absorption through skin (i.e., arms, face)

During brush application and contact with the product if gloves are warn the hand are protected from vapor (area exposed to vapor is reduced by 890 cm2 to 4099 cm2) and it is assumed that 10% of the palm side of

both hands (49 cm2) is exposed to liquid. When no gloves are used the palm side of both hands (490 cm2) is exposed to liquid and only the back side of both hands are exposed to vapor (area exposed to vapor is

reduced by 490 cm2 to 4499 cm2).

# Page 2



# NMP Residential Scenarios

0 months pregnancy 8 months pregnancy



# peak

(Cmax,

mg/L) peak (Cmax,

mg/L) MOE for Cmax MOE for Cmax

1 User User applying brush-on product to a coffee table without

face mask but with gloves on BMDL internal 1% increase in resorptions --

Inhalation and oral developmental studies

(Saillenfait et al. 2002 & 2003)--Preferred

metric: Cmax 0.25 1 0.10 0.08 2244 2613

1 User User applying brush-on product to a coffee table without

gloves or face mask BMDL internal 1% increase in resorptions --

Inhalation and oral developmental studies

(Saillenfait et al. 2002 & 2003)--Preferred

metric: Cmax 0.25 0 0.65 0.56 333 388

1 Non-user in the rest of

the house (ROH) Non-user exposed to NMP vapors resulting from brushon application to a coffee table in adjacent room BMDL internal 1% increase in resorptions --

Inhalation and oral developmental studies

(Saillenfait et al. 2002 & 2003)--Preferred

metric: Cmax NA NA 0.03 0.03 7725 7855 Benchmark MOE=30

Note: Underlined MOEs show risk,

MOE <benchmark MOE

onths pregna months pregnan



# Benchmark Dose Metric and Endpoints Exposure Scenario Receptor Scenario#

based on

Table3-6 of

RA/Tab#1 Dermal?

1="yes" Weight

Fraction

(WF)

# Page 3 0 months pregnancy 8 months pregnancy



# peak

(Cmax,

mg/L) peak (Cmax,

mg/L) MOE for Cmax MOE for Cmax

2 User User applying brush-on product to a coffee table without

face mask but with gloves on BMDL internal 1% increase in resorptions --

Inhalation and oral developmental studies

(Saillenfait et al. 2002 & 2003)--Preferred

metric: Cmax 0.5 1 0.26 0.24 836 912

2 User User applying brush-on product to a coffee table without

gloves or face mask BMDL internal 1% increase in resorptions --

Inhalation and oral developmental studies

(Saillenfait et al. 2002 & 2003)--Preferred

metric: Cmax 0.5 0 1.36 1.17 159 184

2 Non-user in the ROH Non-user exposed to NMP vapors resulting from brushon application to a coffee table in adjacent room BMDL internal 1% increase in resorptions --

Inhalation and oral developmental studies

(Saillenfait et al. 2002 & 2003)--Preferred

metric: Cmax NA NA 0.06 0.06 3862 3927 months pregnan



# Exposure Scenario Benchmark Dose Metric and Endpoints Weight

Fraction

(WF) Dermal?

1="yes" onths pregna Benchmark MOE=30

Note: Underlined MOEs show risk,

MOE<benchmark MOE



# Scenario#

based on

Table3-6 of

RA/Tab#1 Receptor

# Page 4 0 months pregnancy 8 months pregnancy



# peak

(Cmax,

mg/L) peak (Cmax,

mg/L) MOE for Cmax MOE for Cmax

3 User User applying brush-on product to a chest of drawers

without face mask but with gloves on BMDL internal 1% increase in resorptions --

Inhalation and oral developmental studies

(Saillenfait et al. 2002 & 2003)--Preferred

metric: Cmax 0.5 1 0.56 0.48 385 447

3 User User applying brush-on product to a chest of drawers

without gloves or face mask BMDL internal 1% increase in resorptions --

Inhalation and oral developmental studies

(Saillenfait et al. 2002 & 2003)--Preferred

metric: Cmax 0.5 0 2.55 2.15 85 101

3 Non-user in the ROH Non-user exposed to NMP vapors resulting from brushon application to a chest of drawers in adjacent room BMDL internal 1% increase in resorptions --

Inhalation and oral developmental studies

(Saillenfait et al. 2002 & 2003)--Preferred

metric: Cmax NA NA 0.19 0.19 1134 1141 Benchmark MOE=30

Note: Underlined MOEs show risk,

MOE<benchmark MOE

Scenario#

based on

Table3-6 of

RA/Tab#1 Receptor Exposure Scenario Benchmark Dose Metric and Endpoints Weight

Fraction

(WF) Dermal?

1="yes" onths pregna months pregnan

# Page 5 0 months pregnancy 8 months pregnancy



# peak

(Cmax,

mg/L) peak (Cmax,

mg/L) MOE for Cmax MOE for Cmax

4 User User applying brush-on product to a bathtub without

face mask but with gloves on BMDL internal 1% increase in resorptions --

Inhalation and oral developmental studies

(Saillenfait et al. 2002 & 2003)--Preferred

metric: Cmax 0.5 1 4.76 4.12 45.4 52.4

4 User User applying brush-on product to a bathtub without

gloves or face mask BMDL internal 1% increase in resorptions --

Inhalation and oral developmental studies

(Saillenfait et al. 2002 & 2003)--Preferred

metric: Cmax 0.5 0 7.32 6.28 29.5 34.4

4 Non-user in the ROH Non-user exposed to NMP vapors resulting from brushon application to a bathtub in adjacent room BMDL internal 1% increase in resorptions --

Inhalation and oral developmental studies

(Saillenfait et al. 2002 & 2003)--Preferred

metric: Cmax NA NA 0.62 0.61 350 352 Benchmark MOE=30

Note: Underlined MOEs show risk,

MOE<benchmark MOE

Scenario#

based on

Table3-6 of

RA/Tab#1 Receptor Exposure Scenario Benchmark Dose Metric and Endpoints Weight

Fraction

(WF) Dermal?

1="yes" onths pregna months pregnan

# Page 6 0 months pregnancy 8 months pregnancy



# peak

(Cmax,

mg/L) peak (Cmax,

mg/L) MOE for Cmax MOE for Cmax

5 User User applying brush-on product to a bathtub without

face mask but with gloves on BMDL internal 1% increase in resorptions --

Inhalation and oral developmental studies

(Saillenfait et al. 2002 & 2003)--Preferred

metric: Cmax 0.5 1 4.42 3.84 48.9 56.3

5 User User applying brush-on product to a bathtub without

gloves or face mask BMDL internal 1% increase in resorptions --

Inhalation and oral developmental studies

(Saillenfait et al. 2002 & 2003)--Preferred

metric: Cmax 0.5 0 6.98 5.99 30.9 36.1

5 Non-user in the ROH Non-user exposed to NMP vapors resulting from brushon application to a bathtub in adjacent room BMDL internal 1% increase in resorptions --

Inhalation and oral developmental studies

(Saillenfait et al. 2002 & 2003)--Preferred

metric: Cmax NA NA 0.62 0.61 350 352 Benchmark MOE=30

Note: Underlined MOEs show risk,

MOE<benchmark MOE

Scenario#

based on

Table3-6 of

RA/Tab#1 Receptor Exposure Scenario Benchmark Dose Metric and Endpoints Weight

Fraction

(WF) Dermal?

1="yes" onths pregna months pregnan

# Page 7 0 months pregnancy 8 months pregnancy



# peak

(Cmax,

mg/L) peak (Cmax,

mg/L) MOE for Cmax MOE for Cmax

6a User User applying spray-on product to a coffee table without

face mask but with gloves on and remaining in workshop

during wait time BMDL internal 1% increase in resorptions --

Inhalation and oral developmental studies

(Saillenfait et al. 2002 & 2003)--Preferred

metric: Cmax 0.53 1 0.17 0.16 1268.4 1354.8

6a User User applying spray-on product to a coffee table without

gloves or face mask and remaining in workshop during

wait time without gloves or face mask BMDL internal 1% increase in resorptions --

Inhalation and oral developmental studies

(Saillenfait et al. 2002 & 2003)--Preferred

metric: Cmax 0.53 0 0.18 0.17 1203.8 1295.1

6a Non-user in the ROH Non-user exposed to NMP vapors resulting from sprayon product to a coffee table in adjacent room BMDL internal 1% increase in resorptions --

Inhalation and oral developmental studies

(Saillenfait et al. 2002 & 2003)--Preferred

metric: Cmax NA NA 0.04 0.04 4882 4965

0 months pregnancy 8 months pregnancy



# peak

(Cmax,

mg/L) peak (Cmax,

mg/L) MOE for Cmax MOE for Cmax

6b User User applying spray-on product to a coffee table without

face mask but with gloves on and remaining in workshop

during wait time BMDL internal 1% increase in resorptions --

Inhalation and oral developmental studies

(Saillenfait et al. 2002 & 2003)--Preferred

metric: Cmax 0.5 1 1.47 1.30 147.1 166.0

6b User User applying spray-on product to a coffee table without

gloves or face mask and remaining in workshop during

wait time without gloves or face mask BMDL internal 1% increase in resorptions --

Inhalation and oral developmental studies

(Saillenfait et al. 2002 & 2003)--Preferred

metric: Cmax 0.5 0 1.55 1.36 139.8 158.5

6a Non-user in the ROH Non-user exposed to NMP vapors resulting from sprayon product to a coffee table in adjacent room BMDL internal 1% increase in resorptions --

Inhalation and oral developmental studies

(Saillenfait et al. 2002 & 2003)--Preferred

metric: Cmax NA NA 0.35 0.34 619 630

0 months pregnancy 8 months pregnancy



# peak

(Cmax,

mg/L) peak (Cmax,

mg/L) MOE for Cmax MOE for Cmax

7a User User applying spray-on product to a chest of drawers

without face mask but with gloves on and remaining in

workshop during wait time BMDL internal 1% increase in resorptions --

Inhalation and oral developmental studies

(Saillenfait et al. 2002 & 2003)--Preferred

metric: Cmax 0.5 1 0.23 0.21 944.6 1029.0

7a User User applying spray-on product to a chest of drawers

without gloves or face mask and remaining in workshop

during wait time without gloves or face mask BMDL internal 1% increase in resorptions --

Inhalation and oral developmental studies

(Saillenfait et al. 2002 & 2003)--Preferred

metric: Cmax 0.5 0 0.24 0.22 897.6 980.8

7a Non-user in the ROH Non-user exposed to NMP vapors resulting from sprayon product to a chest of drawers in adjacent room BMDL internal 1% increase in resorptions --

Inhalation and oral developmental studies

(Saillenfait et al. 2002 & 2003)--Preferred

metric: Cmax NA NA 0.12 0.12 1802 1832 Weight

Fraction

(WF)

Weight

Fraction

(WF) Dermal?

1="yes" onths pregna months pregnan



# Scenario#

based on

Table3-6 of

RA/Tab#1 Receptor Exposure Scenario Benchmark Dose Metric and Endpoints Weight

Fraction

(WF) Dermal?

1="yes" onths pregna months pregnan 

# Scenario#

based on

Table3-6 of

RA/Tab#1 Receptor Exposure Scenario Benchmark Dose Metric and Endpoints

Dermal?

1="yes" onths pregna months pregnan 

# Scenario#

based on

Table3-6 of

RA/Tab#1 Receptor Exposure Scenario Benchmark Dose Metric and Endpoints

# Page 8 0 months pregnancy 8 months pregnancy



# peak

(Cmax,

mg/L) peak (Cmax,

mg/L) MOE for Cmax MOE for Cmax

7b User User applying spray-on product to a chest of drawers

without face mask but with gloves on and remaining in

workshop during wait time BMDL internal 1% increase in resorptions --

Inhalation and oral developmental studies

(Saillenfait et al. 2002 & 2003)--Preferred

metric: Cmax 0.5 1 1.38 1.30 156.4 166.5

7b User User applying spray-on product to a chest of drawers

without gloves or face mask and remaining in workshop

during wait time without gloves or face mask BMDL internal 1% increase in resorptions --

Inhalation and oral developmental studies

(Saillenfait et al. 2002 & 2003)--Preferred

metric: Cmax 0.5 0 1.45 1.36 149.2 159.4

7b Non-user in the ROH Non-user exposed to NMP vapors resulting from sprayon product to a chest of drawers in adjacent room BMDL internal 1% increase in resorptions --

Inhalation and oral developmental studies

(Saillenfait et al. 2002 & 2003)--Preferred

metric: Cmax NA NA 0.88 0.86 246 251



# Rat internal metrics for resorptions after combined inhalation or oral exposures reported in Saillenfait et al. (2002 & 2003)

BMDL values calculated with internal doses (Values used for MOE estimates)

BMCL01

Cmax (mg/L) 216 

# BENCHMARK DOSE METRICS Scenario#

based on

Table3-6 of

RA/Tab#1 Receptor Exposure Scenario Benchmark Dose Metric and Endpoints Weight

Fraction

(WF) Dermal?

1="yes" onths pregna months pregnan