# NMP residential use exposures: Exposure-Time Course

**Scenarios 1 & 2 (coffee table, brush)** Below, in the set of figures for each scenario, the upper panel(s) show the exposure time-course: air concentration (user and rest-of-house/non-user) plus periods of dermal exposure (“dermal exposure on”, right y-axis). The lower panel(s) show blood concentration time-courses for a residential user without gloves (both dermal and inhalation exposure), residential user with gloves (inhalation only, in the work zone/shop for defined periods), and non-user (rest-of-house; ROH). Dermal exposures to the liquid NMP product are assumed to be on 490 cm2

## of skin for users without gloves. Dermal exposure to the NMP vapor is assumed to be on 6200 cm 2

## for users with gloves and for users without gloves during periods of application/liquid contact. Otherwise 6700 cm 2

## of skin is assumed to be exposed to the vapors.

1

# Scenarios 3 (chest of drawers, brush) [right panel below show blood levels to 24 hours]

2

# Scenarios 4 & 5 (coffee table, spray-workshop)

3

# Scenario 6 (chest of drawers, spray-on workshop) [right panel below show blood levels to 24 hours]

4

# Scenarios 7 & 8 (bathtub, brush)

**Plot of blood levels from combined inhalation and dermal spray-work exposure for 2 weeks:**

5

## NMP Residential Scenarios
**Assumptions:** Consumers and non-users exposed to NMP-based paint strippers based on the scenarios descriptions in Tab#1 (Table 3-6 of draft NMP risk assessment)

→→ Dermal exposure to the NMP vapor is assumed to be on 5860 cm2 for users with gloves and on 6200 cm2 for users without gloves during periods of application/liquid contact. (When gloves are not warn, front of hands are exposed to liquid and backs of hands are exposed to vapor.) Otherwise, 6700 cm2 of skin is assumed to be exposed to the vapors. Maternal blood AUC or Cmax of parent compound used as a surrogate for fetal dose metric

**Preferred dose metrics:** Average AUC24 (mg-hr/L) is preferred for the fetal bodyweight endpoint assuming that a sustained internal dose of parent compound is needed to induce changes in fetal body weights Cmax (mg/L) is preferred for fetal skeletal anomalies 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 cm2 of skin for users without gloves. All of the exposure scenarios assumed vapor absorption through skin (i.e., arms, face)

Page 1

## NMP Residential Scenarios

avg AUC (mg-hr/L) peak

(Cmax, mg/L) avg AUC (mg-hr/L) peak

(Cmax, mg/L) MOE for avg AUC MOE for

Cmax MOE for

avg AUC MOE for

avg Cmax

1 User Inhalation exposure only/ User applying brush-on product without face mask but with gloves on BMDL internal dose values for 5% reduction in fetal BW--Inhalation developmental study (Saillenfait et al. 2003)--Preferred metric:

AUC 0.25 0 0.74 0.14 0.75 0.14 332.4 219.3 328.0 212.3

1 User Inhalation and dermal exposure/ User applying brush-on product without gloves and face mask BMDL internal dose values for 5% reduction in fetal BW--Inhalation developmental study (Saillenfait et al. 2003)--Preferred metric:

AUC 0.25 1 3.87 2.70 3.88 2.35 63.5 **11.4** 63.4 **13.0**

1 User Inhalation and dermal exposure/ User applying brush-on product without gloves and face mask NOAEL for maternal and fetal toxicity

-- Dermal developmental toxicity study (Becci et al. 1982)--Preferred metric: AUC 0.25 1 3.87 2.70 3.88 2.35 357.5 237.8 357.2 272.3

1 User Inhalation and dermal exposure/ User applying brush-on product without gloves and face mask BMDL internal dose values for 5% increase in fetal skeletal anomalies --Pooled internal doses from inhalation and dermal studies (Saillenfait et al. 2003 and Becci et al., 1982)--

Preferred metric: Cmax 0.25 1 3.87 2.70 3.88 2.35 Not calculated 

## 10.0 Not

calculated 

## 11.5

1 Non-user in the rest

of the house (ROH) Inhalation and dermal exposure / Non-user breathing NMP vapors resulting from brush-on application in adjacent room BMDL internal dose values for 5% reduction in fetal BW--Inhalation developmental study (Saillenfait et al. 2003)--Preferred metric:

AUC 0 0 0.55 0.08 0.56 0.07 448.1 399.5 442.3 410.6

1 Non-user in the rest

of the house (ROH) Inhalation and dermal exposure / Non-user breathing NMP vapors resulting from brush-on application in adjacent room NOAEL for maternal and fetal toxicity

-- Dermal developmental toxicity study (Becci et al. 1982)--Preferred metric: AUC 0 0 0.55 0.08 0.56 0.07 2522.7 8341.9 2490.3 8573.4

1 Non-user in the rest

of the house (ROH) Inhalation and dermal exposure / Non-user breathing NMP vapors resulting from brush-on application in adjacent room BMDL internal dose values for 5% increase in fetal skeletal anomalies --Pooled internal doses from inhalation and dermal studies (Saillenfait et al. 2003 and Becci et al., 1982)--

Preferred metric: Cmax 0 0 0.55 0.08 0.56 0.07 Not calculated 351.4 Not

calculated 361.1 **Benchmark Dose Metric and Endpoints Exposure Scenario**  **Receptor Scenario#**  **based on Table3-6 of**  **RA/Tab#1 Dermal?**  **1="yes" Weight**  **Fraction (WF)**  **Benchmark MOE=30 Note: Preferred metrics are those**  **highlighted in red text** **. Underlined MOEs show risk, MOE** **<benchmark MOE 0 months pregnancy**  **8 months pregnancy 0 months pregnancy**  **8 months pregnancy**

Page 2avg AUC (mg-hr/L) peak

(Cmax, mg/L) avg AUC (mg-hr/L) peak

(Cmax, mg/L) MOE for avg AUC MOE for

Cmax MOE for

avg AUC MOE for

avg Cmax

2 User Inhalation exposure only/ User applying brush-on product without face mask but with gloves on BMDL internal dose values for 5% reduction in fetal BW--Inhalation developmental study (Saillenfait et al. 2003)--Preferred metric:

AUC 0.5 0 2.97 0.68 3.00 0.61 82.8 45.1 82.0 50.3

2 User Inhalation and dermal exposure/ User applying brush-on product without gloves and face mask BMDL internal dose values for 5% reduction in fetal BW--Inhalation developmental study (Saillenfait et al. 2003)--Preferred metric:

AUC 0.5 1 9.30 5.55 9.32 4.86 

## 26.5 **5.5** 

## 26.4 **6.3**

2 User Inhalation and dermal exposure/ User applying brush-on product without gloves and face mask NOAEL for maternal and fetal toxicity

-- Dermal developmental toxicity study (Becci et al. 1982)--Preferred metric: AUC 0.5 1 9.30 5.55 9.32 4.86 149.0 115.4 148.6 131.9

2 User Inhalation and dermal exposure/ User applying brush-on product without gloves and face mask BMDL internal dose values for 5% increase in fetal skeletal anomalies --Pooled internal doses from inhalation and dermal studies (Saillenfait et al. 2003 and Becci et al., 1982)--

Preferred metric: Cmax 0.5 1 9.30 5.55 9.32 4.86 Not calculated 

## 4.9 Not

calculated 

## 5.6

2 Non-user in the ROH Inhalation and dermal exposure / Non-user breathing NMP vapors resulting from brush-on application in adjacent room BMDL internal dose values for 5% reduction in fetal BW--Inhalation developmental study (Saillenfait et al. 2003)--Preferred metric:

AUC 0 0 1.10 0.15 1.11 0.15 224.0 199.7 221.1 205.3

2 Non-user in the ROH Inhalation and dermal exposure / Non-user breathing NMP vapors resulting from brush-on application in adjacent room NOAEL for maternal and fetal toxicity

-- Dermal developmental toxicity study (Becci et al. 1982)--Preferred metric: AUC 0 0 1.10 0.15 1.11 0.15 1260.9 4170.0 1244.7 4285.8

2 Non-user in the ROH Inhalation and dermal exposure / Non-user breathing NMP vapors resulting from brush-on application in adjacent room BMDL internal dose values for 5% increase in fetal skeletal anomalies --Pooled internal doses from inhalation and dermal studies (Saillenfait et al. 2003 and Becci et al., 1982)--

Preferred metric: Cmax 0 0 1.10 0.15 1.11 0.15 Not calculated 175.6 Not

calculated 180.5 **Benchmark MOE=30 Note: Preferred metrics are those**  **highlighted in red text** **. 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" 0 months pregnancy**  **8 months pregnancy 0 months pregnancy**  **8 months pregnancy**

Page 3avg AUC (mg-hr/L) peak

(Cmax, mg/L) avg AUC (mg-hr/L) peak

(Cmax, mg/L) MOE for avg AUC MOE for

Cmax MOE for

avg AUC MOE for

avg Cmax

3 User Inhalation exposure only/ User applying brush-on product without face mask but with gloves on BMDL internal dose values for 5% reduction in fetal BW--Inhalation developmental study (Saillenfait et al. 2003)--Preferred metric:

AUC 0.5 0 8.36 1.38 8.47 1.22 

## 29.4 22.2 

## 29.0 25.2

3 User Inhalation and dermal exposure/ User applying brush-on product without gloves and face mask BMDL internal dose values for 5% reduction in fetal BW--Inhalation developmental study (Saillenfait et al. 2003)--Preferred metric:

AUC 0.5 1 24.49 10.25 24.54 8.67 

## 10.0 **3.0** 

## 10.0 **3.5**

3 User Inhalation and dermal exposure/ User applying brush-on product without gloves and face mask NOAEL for maternal and fetal toxicity

-- Dermal developmental toxicity study (Becci et al. 1982)--Preferred metric: AUC 0.5 1 24.49 10.25 24.54 8.67 56.6 62.5 56.4 73.9

3 User Inhalation and dermal exposure/ User applying brush-on product without gloves and face mask BMDL internal dose values for 5% increase in fetal skeletal anomalies --Pooled internal doses from inhalation and dermal studies (Saillenfait et al. 2003 and Becci et al., 1982)--

Preferred metric: Cmax 0.5 1 24.49 10.25 24.54 8.67 Not calculated 

## 2.6 Not

calculated 

## 3.1

3 Non-user in the ROH Inhalation and dermal exposure / Non-user breathing NMP vapors resulting from brush-on application in adjacent room BMDL internal dose values for 5% reduction in fetal BW--Inhalation developmental study (Saillenfait et al. 2003)--Preferred metric:

AUC 0 0 5.43 0.52 5.50 0.53 45.3 58.5 44.7 58.3

3 Non-user in the ROH Inhalation and dermal exposure / Non-user breathing NMP vapors resulting from brush-on application in adjacent room NOAEL for maternal and fetal toxicity

-- Dermal developmental toxicity study (Becci et al. 1982)--Preferred metric: AUC 0 0 5.43 0.52 5.50 0.53 255.1 1221.9 251.9 1217.3

3 Non-user in the ROH Inhalation and dermal exposure / Non-user breathing NMP vapors resulting from brush-on application in adjacent room BMDL internal dose values for 5% increase in fetal skeletal anomalies --Pooled internal doses from inhalation and dermal studies (Saillenfait et al. 2003 and Becci et al., 1982)--

Preferred metric: Cmax 0 0 5.43 0.52 5.50 0.53 Not calculated 51.5 Not

calculated 51.3 **Benchmark MOE=30 Note: Preferred metrics are those**  **highlighted in red text** **. 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" 0 months pregnancy**  **8 months pregnancy 0 months pregnancy**  **8 months pregnancy**

Page 4avg AUC (mg-hr/L) peak

(Cmax, mg/L) avg AUC (mg-hr/L) peak

(Cmax, mg/L) MOE for avg AUC MOE for

Cmax MOE for

avg AUC MOE for

avg Cmax

4 User Inhalation exposure only/ User applying spray-on product without face mask but with gloves on BMDL internal dose values for 5% reduction in fetal BW--Inhalation developmental study (Saillenfait et al. 2003)--Preferred metric:

AUC 0.44 0 1.88 0.42 1.90 0.36 130.9 73.1 129.5 85.3

4 User Inhalation and dermal exposure/ User applying spray-on product without gloves and face mask BMDL internal dose values for 5% reduction in fetal BW--Inhalation developmental study (Saillenfait et al. 2003)--Preferred metric:

AUC 0.44 1 4.63 2.94 4.65 2.60 53.1 **10.4** 52.9 **11.8**

4 User Inhalation and dermal exposure/ User applying spray-on product without gloves and face mask NOAEL for maternal and fetal toxicity

-- Dermal developmental toxicity study (Becci et al. 1982)--Preferred metric: AUC 0.44 1 4.63 2.94 4.65 2.60 299.0 217.8 297.7 246.5

4 User Inhalation and dermal exposure/ User applying spray-on product without gloves and face mask BMDL internal dose values for 5% increase in fetal skeletal anomalies --Pooled internal doses from inhalation and dermal studies (Saillenfait et al. 2003 and Becci et al., 1982)--

Preferred metric: Cmax 0.44 1 4.63 2.94 4.65 2.60 Not calculated 

## 9.2 Not

calculated 

## 10.4

4 Non-user in the ROH Inhalation and dermal exposure / Non-user breathing NMP vapors resulting from spray-on application in adjacent room BMDL internal dose values for 5% reduction in fetal BW--Inhalation developmental study (Saillenfait et al. 2003)--Preferred metric: 0 0 1.43 0.20 1.45 0.19 172.4 153.5 170.2 157.8

4 Non-user in the ROH Inhalation and dermal exposure / Non-user breathing NMP vapors resulting from spray-on application in adjacent room NOAEL for maternal and fetal toxicity

-- Dermal developmental toxicity study (Becci et al. 1982)--Preferred metric: AUC 0 0 1.43 0.20 1.45 0.19 970.5 3204.8 958.1 3294.5

4 Non-user in the ROH Inhalation and dermal exposure / Non-user breathing NMP vapors resulting from spray-on application in adjacent room BMDL internal dose values for 5% increase in fetal skeletal anomalies --Pooled internal doses from inhalation and dermal studies (Saillenfait et al. 2003 and Becci et al., 1982)--

Preferred metric: Cmax 0 0 1.43 0.20 1.45 0.19 Not calculated 135.0 Not

calculated 138.8 **Benchmark MOE=30 Note: Preferred metrics are those**  **highlighted in red text** **. 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" 0 months pregnancy**  **8 months pregnancy 0 months pregnancy**  **8 months pregnancy**

Page 5avg AUC (mg-hr/L) peak

(Cmax, mg/L) avg AUC (mg-hr/L) peak

(Cmax, mg/L) MOE for avg AUC MOE for

Cmax MOE for

avg AUC MOE for

avg Cmax

5 User Inhalation exposure only/ User applying spray-on product without face mask but with gloves on BMDL internal dose values for 5% reduction in fetal BW--Inhalation developmental study (Saillenfait et al. 2003)--Preferred metric:

AUC 0.53 0 4.63 1.09 4.69 0.97 53.1 28.2 52.5 31.6

5 User Inhalation and dermal exposure/ User applying spray-on product without gloves and face mask BMDL internal dose values for 5% reduction in fetal BW--Inhalation developmental study (Saillenfait et al. 2003)--Preferred metric:

AUC 0.53 1 8.02 3.82 8.07 3.38 30.7 **8.0** 30.5 **9.1**

5 User Inhalation and dermal exposure/ User applying spray-on product without gloves and face mask NOAEL for maternal and fetal toxicity

-- Dermal developmental toxicity study (Becci et al. 1982)--Preferred metric: AUC 0.53 1 8.02 3.82 8.07 3.38 172.7 167.7 171.6 189.7

5 User Inhalation and dermal exposure/ User applying spray-on product without gloves and face mask BMDL internal dose values for 5% increase in fetal skeletal anomalies --Pooled internal doses from inhalation and dermal studies (Saillenfait et al. 2003 and Becci et al., 1982)--

Preferred metric: Cmax 0.53 1 8.02 3.82 8.07 3.38 Not calculated 

## 7.1 Not

calculated 

## 8.0

5 Non-user in the ROH Inhalation and dermal exposure / Non-user breathing NMP vapors resulting from spray-on application in adjacent room BMDL internal dose values for 5% reduction in fetal BW--Inhalation developmental study (Saillenfait et al. 2003)--Preferred metric:

AUC 0 0 1.72 0.24 1.74 0.23 143.1 127.4 141.2 131.0

5 Non-user in the ROH Inhalation and dermal exposure / Non-user breathing NMP vapors resulting from spray-on application in adjacent room NOAEL for maternal and fetal toxicity

-- Dermal developmental toxicity study (Becci et al. 1982)--Preferred metric: AUC 0 0 1.72 0.24 1.74 0.23 805.5 2660.1 795.2 2734.7

5 Non-user in the ROH Inhalation and dermal exposure / Non-user breathing NMP vapors resulting from spray-on application in adjacent room BMDL internal dose values for 5% increase in fetal skeletal anomalies --Pooled internal doses from inhalation and dermal studies (Saillenfait et al. 2003 and Becci et al., 1982)--

Preferred metric: Cmax 0 0 1.72 0.24 1.74 0.23 Not calculated 112.0 Not

calculated 115.2 **Benchmark MOE=30 Note: Preferred metrics are those**  **highlighted in red text** **. 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" 0 months pregnancy**  **8 months pregnancy 0 months pregnancy**  **8 months pregnancy**

Page 6avg AUC (mg-hr/L) peak

(Cmax, mg/L) avg AUC (mg-hr/L) peak

(Cmax, mg/L) MOE for avg AUC MOE for

Cmax MOE for

avg AUC MOE for

avg Cmax

6 User Inhalation exposure only/ User applying spray-on product without face mask but with gloves on BMDL internal dose values for 5% reduction in fetal BW--Inhalation developmental study (Saillenfait et al. 2003)--Preferred metric:

AUC 0.53 0 12.50 2.13 12.67 1.85 

## 19.7 14.4 

## 19.4 16.6

6 User Inhalation and dermal exposure/ User applying spray-on product without gloves and face mask BMDL internal dose values for 5% reduction in fetal BW--Inhalation developmental study (Saillenfait et al. 2003)--Preferred metric:

AUC 0.53 1 21.16 7.60 21.30 6.57 

## 11.6 **4.0** 

## 11.5 **4.7**

6 User Inhalation and dermal exposure/ User applying spray-on product without gloves and face mask NOAEL for maternal and fetal toxicity

-- Dermal developmental toxicity study (Becci et al. 1982)--Preferred metric: AUC 0.53 1 21.16 7.60 21.30 6.57 65.4 84.3 65.0 97.6

6 User Inhalation and dermal exposure/ User applying spray-on product without gloves and face mask BMDL internal dose values for 5% increase in fetal skeletal anomalies --Pooled internal doses from inhalation and dermal studies (Saillenfait et al. 2003 and Becci et al., 1982)--

Preferred metric: Cmax 0.53 1 21.16 7.60 21.30 6.57 Not calculated 

## 3.6 Not

calculated 

## 4.1

6 Non-user in the ROH Inhalation and dermal exposure / Non-user breathing NMP vapors resulting from spray-on application in adjacent room BMDL internal dose values for 5% reduction in fetal BW--Inhalation developmental study (Saillenfait et al. 2003)--Preferred metric:

AUC 0 0 8.40 0.81 8.50 0.82 

## 29.3 37.8 

## 28.9 37.6

6 Non-user in the ROH Inhalation and dermal exposure / Non-user breathing NMP vapors resulting from spray-on application in adjacent room NOAEL for maternal and fetal toxicity

-- Dermal developmental toxicity study (Becci et al. 1982)--Preferred metric: AUC 0 0 8.40 0.81 8.50 0.82 165.0 788.9 162.9 785.9

6 Non-user in the ROH Inhalation and dermal exposure / Non-user breathing NMP vapors resulting from spray-on application in adjacent room BMDL internal dose values for 5% increase in fetal skeletal anomalies --Pooled internal doses from inhalation and dermal studies (Saillenfait et al. 2003 and Becci et al., 1982)--

Preferred metric: Cmax 0 0 8.40 0.81 8.50 0.82 Not calculated 33.2 Not

calculated 33.1 **Benchmark MOE=30 Note: Preferred metrics are those**  **highlighted in red text** **. 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"**  **0 months pregnancy 8 months pregnancy**  **0 months pregnancy 8 months pregnancy** 

Page 7avg AUC (mg-hr/L) peak

(Cmax, mg/L) avg AUC (mg-hr/L) peak

(Cmax, mg/L) MOE for avg AUC MOE for

Cmax MOE for

avg AUC MOE for

avg Cmax

7 User Inhalation exposure only/ User applying brush-on product without face mask but with gloves on BMDL internal dose values for 5% reduction in fetal BW--Inhalation developmental study (Saillenfait et al. 2003)--Preferred metric:

AUC 0.5 0 62.62 13.29 63.38 12.05 

## 3.9 2.3 

## 3.9 2.5

7 User Inhalation and dermal exposure/ User applying brush-on product without gloves and face mask BMDL internal dose values for 5% reduction in fetal BW--Inhalation developmental study (Saillenfait et al. 2003)--Preferred metric:

AUC 0.5 1 88.20 21.50 88.83 18.42 

## 2.8 **1.4** 

## 2.8 **1.7**

7 User Inhalation and dermal exposure/ User applying brush-on product without gloves and face mask NOAEL for maternal and fetal toxicity

-- Dermal developmental toxicity study (Becci et al. 1982)--Preferred metric: AUC 0.5 1 88.20 21.50 88.83 18.42 

## 15.7 29.8 

## 15.6 34.8

7 User Inhalation and dermal exposure/ User applying brush-on product without gloves and face mask BMDL internal dose values for 5% increase in fetal skeletal anomalies --Pooled internal doses from inhalation and dermal studies (Saillenfait et al. 2003 and Becci et al., 1982)--

Preferred metric: Cmax 0.5 1 88.20 21.50 88.83 18.42 Not calculated 

## 1.3 Not

calculated 

## 1.5

7 Non-user in the ROH Inhalation and dermal exposure / Non-user breathing NMP vapors resulting from brush-on application in adjacent room BMDL internal dose values for 5% reduction in fetal BW--Inhalation developmental study (Saillenfait et al. 2003)--Preferred metric:

AUC 0 0 19.20 1.58 19.42 1.60 

## 12.8 19.4 

## 12.7 19.2

7 Non-user in the ROH Inhalation and dermal exposure / Non-user breathing NMP vapors resulting from brush-on application in adjacent room NOAEL for maternal and fetal toxicity

-- Dermal developmental toxicity study (Becci et al. 1982)--Preferred metric: AUC 0 0 19.20 1.58 19.42 1.60 72.1 405.2 71.3 401.2

7 Non-user in the ROH Inhalation and dermal exposure / Non-user breathing NMP vapors resulting from brush-on application in adjacent room BMDL internal dose values for 5% increase in fetal skeletal anomalies --Pooled internal doses from inhalation and dermal studies (Saillenfait et al. 2003 and Becci et al., 1982)--

Preferred metric: Cmax 0 0 19.20 1.58 19.42 1.60 Not calculated 

## 17.1 Not

calculated 

## 16.9 **Benchmark MOE=30 Note: Preferred metrics are those**  **highlighted in red text** **. 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" 0 months pregnancy**  **8 months pregnancy 0 months pregnancy**  **8 months pregnancy**

Page 8avg AUC (mg-hr/L) peak

(Cmax, mg/L) avg AUC (mg-hr/L) peak

(Cmax, mg/L) MOE for avg AUC MOE for

Cmax MOE for

avg AUC MOE for

avg Cmax

8 User Inhalation exposure only/ User applying brush-on product without face mask but with gloves on BMDL internal dose values for 5% reduction in fetal BW--Inhalation developmental study (Saillenfait et al. 2003)--Preferred metric:

AUC 0.5 0 36.81 7.16 37.27 6.64 

## 6.7 4.3 

## 6.6 4.6

8 User Inhalation and dermal exposure/ User applying brush-on product without gloves and face mask BMDL internal dose values for 5% reduction in fetal BW--Inhalation developmental study (Saillenfait et al. 2003)--Preferred metric:

AUC 0.5 1 61.32 17.42 61.67 14.92 

## 4.0 **1.8** 

## 4.0 **2.1**

8 User Inhalation and dermal exposure/ User applying brush-on product without gloves and face mask NOAEL for maternal and fetal toxicity

-- Dermal developmental toxicity study (Becci et al. 1982)--Preferred metric: AUC 0.5 1 61.32 17.42 61.67 14.92 

## 22.6 36.8 

## 22.5 43.0

8 User Inhalation and dermal exposure/ User applying brush-on product without gloves and face mask BMDL internal dose values for 5% increase in fetal skeletal anomalies --Pooled internal doses from inhalation and dermal studies (Saillenfait et al. 2003 and Becci et al., 1982)--

Preferred metric: Cmax 0.5 1 61.32 17.42 61.67 14.92 Not calculated 

## 1.6 Not

calculated 

## 1.8

8 Non-user in the ROH Inhalation and dermal exposure / Non-user breathing NMP vapors resulting from brush-on application in adjacent room BMDL internal dose values for 5% reduction in fetal BW--Inhalation developmental study (Saillenfait et al. 2003)--Preferred metric:

AUC 0 0 11.36 0.94 11.49 0.95 

## 21.7 32.8 

## 21.4 32.5

8 Non-user in the ROH Inhalation and dermal exposure / Non-user breathing NMP vapors resulting from brush-on application in adjacent room NOAEL for maternal and fetal toxicity

-- Dermal developmental toxicity study (Becci et al. 1982)--Preferred metric: AUC 0 0 11.36 0.94 11.49 0.95 122.0 684.4 120.5 677.7

8 Non-user in the ROH Inhalation and dermal exposure / Non-user breathing NMP vapors resulting from brush-on application in adjacent room BMDL internal dose values for 5% increase in fetal skeletal anomalies --Pooled internal doses from inhalation and dermal studies (Saillenfait et al. 2003 and Becci et al., 1982)--

Preferred metric: Cmax 0 0 11.36 0.94 11.49 0.95 Not calculated 

## 28.8 Not

calculated 

## 28.5 **Benchmark MOE=30 Note: Preferred metrics are those**  **highlighted in red text** **. 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" 0 months pregnancy**  **8 months pregnancy 0 months pregnancy**  **8 months pregnancy**

Page 9

## BENCHMARK DOSE METRICS **Rat internal metrics for GD 6-20 inhalation exposures reported in Saillenfait et al. (2003)**

External air

conc Average AUC24 (mghr/L) Cmax (mg/L) Fetal BW (g) ±Std Dev
0 0 0 5.67±0.37 122 94 12 5.62±0.36 243 191 24 5.47±0.25 487 397 50 5.39±0.45* *Significant difference from the control (air), P<0.05
**BMDL values calculated with internal doses (Values used for MOE estimates)**

BMCL05 average AUC24-hr (mghr/L) **246**

BMCL05 Cmax (mg/L) **30.7**



### Rat internal metrics for GD 6-15 dermal exposures, but averaged over GD 6-21 reported in Becci et al. (1982) mg/kg-d Average AUC 24-hr

(mg-hr/L) Cmax (mg/L)
0 0 0 75 359 202 237 **1385 641**  237 mg/kg-day is the NOAEL for maternal and fetal toxicity (increased resorption, fewer 750 6000 2050 live fetuses, reduced body weight, skeletal abnormalities)



### Combined Becci et al. (1982) dermal and Saillenfait et al. (2003) inhalation data for vertebrae/incomplete ossification

BMCL05 Cmax (mg/L) **27**

Page 10