TCE Occupational Scenarios

Assumptions: 

Workers exposed to NMP-based paint strippers for 8 h/day, 5/d week, with a 30 min break after the first 4 h of exposure

Skin exposed to vapor: 6700-840=5860 cm^2 (even when inhalation exposure is off, skin absorption can occur), except first six rows

Skin exposed to liquid/spray: 840 cm^2m except when dermal=0, when this area is assumed to be protected/accluded (0.01 cm^2 used to avoid divide-by-zero)

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. 

1
TCE Occupational Scenarios

dermal air conc.

rate 

(mg/h) mg/m^3 avg AUC 

(mg-hr/L)

peak 

(Cmax, 

mg/L))

avg AUC 

(mg-hr/L)

peak 

(C max, 

mg/L)

MOE for 

avg AUC

MOE for 

Cmax

MOE for avg 

AUC

MOE for 

Cmax

Dermal exposure only / Worker with exposed hands handling 

NMP-based paint stripper (liquid or spray product) but wearing 

a face mask /No vapor absorption through skin (minimal skin 

area exposed other than hands) / Lower dermal rate 

NOAEL for maternal and fetal 

toxicity--Dermal 

developmental toxicity study 

(Becci et al. 1982)--Preferred 

metric: AUC

74 0 22.69 3.54 22.66 3.50 61.0 180.9 61.1 183.1

Dermal exposure only / Worker with exposed hands but 

wearing a face mask /No vapor absorption through skin 

(minimal skin area exposed other than hands) / Higher dermal 

rate

NOAEL for maternal and fetal 

toxicity--Dermal 

developmental toxicity study 

(Becci et al. 1982)--Preferred 

metric: AUC

225 0 70.54 11.03 70.43 10.89 19.6 58.1 19.7 58.9

Dermal exposure only / Worker with exposed hands handling 

NMP-based paint stripper (liquid or spray product) but wearing 

a face mask /No vapor absorption through skin (minimal skin 

area exposed other than hands) / Lower dermal rate 

BMDL internal dose values 

for 5% reduction in fetal BW--

Inhalation developmental 

study (Saillenfait et al. 2003)--

Preferred metric: AUC

74 0 22.69 3.54 22.66 3.50 10.8 8.7 10.9 8.8

Dermal exposure only / Worker with exposed hands but 

wearing a face mask /No vapor absorption through skin 

(minimal skin area exposed other than hands) / Higher dermal 

rate

BMDL internal dose values 

for 5% reduction in fetal BW--

Inhalation developmental 

study (Saillenfait et al. 2003)--

Preferred metric: AUC

225 0 70.54 11.03 70.43 10.89 3.5 2.8 3.5 2.8

Dermal exposure only / Worker with exposed hands handling 

NMP-based paint stripper (liquid or spray product) but wearing 

a face mask /No vapor absorption through skin (minimal skin 

area exposed other than hands) / Lower dermal rate 

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

74 0 22.69 3.54 22.66 3.50 Not 

calculated 7.6 Not calculated 7.7

Dermal exposure only / Worker with exposed hands but 

wearing a face mask /No vapor absorption through skin 

(minimal skin area exposed other than hands) / Higher dermal 

rate

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

225 0 70.54 11.03 70.43 10.89 Not 

calculated 2.4 Not calculated 2.5

Benchmark MOE=30 

Note: Preferred metrics are those highlighted in 

red text. Underlined MOEs show risks, MOE< 

benchmark MOE

0 months pregnancy 8 months pregnancy

Exposure Scenario Benchmark Dose Metric and 

Endpoints 

0 months pregnancy 8 months pregnancy

2
dermal air conc.

rate 

(mg/h) mg/m^3 avg AUC (mg-hr/L)

peak 

(Cmax, 

mg/L))

avg AUC 

(mg-hr/L)

peak 

(C max, 

mg/L)

MOE for 

avg AUC

MOE for 

Cmax

MOE for avg 

AUC

MOE for 

Cmax

Dermal exposure only / Worker with exposed hands in contact 

with liquid form but wearing a face mask / Vapor absorption 

through other areas of exposed skin (i.e., arms, face) / Lower 

dermal rate, lower NMP air concentration

NOAEL for maternal and fetal 

toxicity--Dermal 

developmental toxicity study 

(Becci et al. 1982)--Preferred 

metric: AUC

74 13 22.92 3.60 22.89 3.56 60.4 178.2 60.5 180.0

Dermal exposure only / Worker with exposed hands in contact 

with liquid form but wearing a face mask / Vapor absorption 

through other areas of exposed skin (i.e., arms, face) / Higher 

dermal rate, higher NMP air concentration

NOAEL for maternal and fetal 

toxicity--Dermal 

developmental toxicity study 

(Becci et al. 1982)--Preferred 

metric: AUC

225 39 71.21 11.19 71.11 11.07 19.4 57.3 19.5 57.9

Dermal exposure only / Worker with exposed hands in contact 

with liquid form but wearing a face mask / Vapor absorption 

through other areas of exposed skin (i.e., arms, face) / Lower 

dermal rate, lower NMP air concentration

BMDL internal dose values 

for 5% reduction in fetal BW--

Inhalation developmental 

study (Saillenfait et al. 2003)--

Preferred metric: AUC

74 13 22.92 3.60 22.89 3.56 10.7 8.5 10.7 8.6

Dermal exposure only / Worker with exposed hands in contact 

with liquid form but wearing a face mask / Vapor absorption 

through other areas of exposed skin (i.e., arms, face) / Higher 

dermal rate, higher NMP air concentration

BMDL internal dose values 

for 5% reduction in fetal BW--

Inhalation developmental 

study (Saillenfait et al. 2003)--

Preferred metric: AUC

225 39 71.21 11.19 71.11 11.07 3.5 2.7 3.5 2.8

Dermal exposure only / Worker with exposed hands in contact 

with liquid form but wearing a face mask / Vapor absorption 

through other areas of exposed skin (i.e., arms, face) / Lower 

dermal rate, lower NMP air concentration

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

74 13 22.92 3.60 22.89 3.56 Not 

calculated 7.5 Not calculated 7.6

Dermal exposure only / Worker with exposed hands in contact 

with liquid form but wearing a face mask / Vapor absorption 

through other areas of exposed skin (i.e., arms, face) / Higher 

dermal rate, higher NMP air concentration

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

225 39 71.21 11.19 71.11 11.07 Not 

calculated 2.4 Not calculated 2.4

0 months pregnancy 8 months pregnancy

Exposure Scenario 

NOTE: Preferred scenarios are those highlighted in red text.

Benchmark Dose Metric

0 months pregnancy 8 months pregnancy

3
dermal air conc.

rate 

(mg/h) mg/m^3 avg AUC (mg-hr/L)

peak 

(Cmax, 

mg/L))

avg AUC 

(mg-hr/L)

peak 

(C max, 

mg/L)

MOE for 

avg AUC

MOE for 

Cmax

MOE for avg 

AUC

MOE for 

Cmax

Inhalation exposure only / Worker wearing gloves but no face 

mask / Inhalation with skin absorption of NMP vapor through 

other areas of exposed skin (i.e., arms, face) / Lower NMP air 

concentration (NOTE: if skin absorption turned off, values 

reduced ~ 40%)

BMDL internal dose values 

for 5% reduction in fetal BW--

Inhalation developmental 

study (Saillenfait et al. 2003)--

Preferred metric: AUC

0 13 1.72 0.26 1.75 0.26 142.9 117.9 140.8 116.6

Inhalation exposure only / Worker wearing gloves but no face 

mask / Inhalation with skin absorption of vapor through other 

areas of exposed skin (i.e., arms, face) / Higher NMP air 

concentration (NOTE: if skin absorption turned off, values 

reduced ~ 40%)

BMDL internal dose values 

for 5% reduction in fetal BW--

Inhalation developmental 

study (Saillenfait et al. 2003)--

Preferred metric: AUC

0 39 5.18 0.78 5.25 0.79 47.5 39.2 46.8 38.8

Inhalation exposure only / Worker wearing gloves but no face 

mask / Inhalation with skin absorption of NMP vapor through 

other areas of exposed skin (i.e., arms, face) / Lower NMP air 

concentration (NOTE: if skin absorption turned off, values 

reduced ~ 40%)

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 13 1.72 0.26 1.75 0.26 Not 

calculated 103.7 Not calculated 102.5

Inhalation exposure only / Worker wearing gloves but no face 

mask / Inhalation with skin absorption of vapor through other 

areas of exposed skin (i.e., arms, face) / Higher NMP air 

concentration (NOTE: if skin absorption turned off, values 

reduced ~ 40%)

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 39 5.18 0.78 5.25 0.79 Not 

calculated 34.5 Not calculated 34.1

0 months pregnancy 8 months pregnancy

Exposure Scenario 

NOTE: Preferred scenarios are those highlighted in red text.

Benchmark Dose Metric

0 months pregnancy 8 months pregnancy

4
dermal air conc.

rate 

(mg/h) mg/m^3 avg AUC (mg-hr/L)

peak 

(Cmax, 

mg/L))

avg AUC 

(mg-hr/L)

peak 

(C max, 

mg/L)

MOE for 

avg AUC

MOE for 

Cmax

MOE for avg 

AUC

MOE for 

Cmax

Combined dermal, inhalation, and vapor-through-skin 

exposures / Worker with exposed hands and no face mask / 

Lower dermal rate, lower NMP air concentration

NOAEL for maternal and fetal 

toxicity--Dermal 

developmental toxicity study 

(Becci et al. 1982)--Preferred 

metric: AUC

74 13 23.98 3.75 23.98 3.72 57.8 170.7 57.8 172.2

Combined dermal, inhalation, and vapor-through-skin 

exposures / Worker with exposed hands and no face mask / 

Higher dermal rate, higher NMP air concentration

NOAEL for maternal and fetal 

toxicity--Dermal 

developmental toxicity study 

(Becci et al. 1982)--Preferred 

metric: AUC

225 39 74.54 11.69 74.52 11.57 18.6 54.8 18.6 55.4

Combined dermal, inhalation, and vapor-through-skin 

exposures / Worker with exposed hands and no face mask / 

Lower dermal rate, lower NMP air concentration

BMDL internal dose values 

for 5% reduction in fetal BW--

Inhalation developmental 

study (Saillenfait et al. 2003)--

Preferred metric: AUC

74 13 23.98 3.75 23.98 3.72 10.3 8.2 10.3 8.2

Combined dermal, inhalation, and vapor-through-skin 

exposures / Worker with exposed hands and no face mask / 

Higher dermal rate, higher NMP air concentration

BMDL internal dose values 

for 5% reduction in fetal BW--

Inhalation developmental 

study (Saillenfait et al. 2003)--

Preferred metric: AUC

225 39 74.54 11.69 74.52 11.57 3.3 2.6 3.3 2.7

Combined dermal, inhalation, and vapor-through-skin 

exposures / Worker with exposed hands and no face mask / 

Lower dermal rate, lower NMP air concentration

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

74 13 23.98 3.75 23.98 3.72 Not 

calculated 7.2 Not calculated 7.3

Combined dermal, inhalation, and vapor-through-skin 

exposures / Worker with exposed hands and no face mask / 

Higher dermal rate, higher NMP air concentration

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

225 39 74.54 11.69 74.52 11.57

Not 

calculated 2.3 Not calculated 2.3

0 months pregnancy 8 months pregnancy

Exposure Scenario 

NOTE: Preferred scenarios are those highlighted in red text.

Benchmark Dose Metric

0 months pregnancy 8 months pregnancy

5
BENCHMARK DOSE METRICS

Rat internal metrics for GD 6-20 inhalation exposures reported in Saillenfait et al. (2003) 

External air conc (mg/m3)

Average AUC24 (mg-hr/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 AUC 24-hr (mg-hr/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

6