20.51e
                                     4.39
                                    17.74e
                                     1.51
CO2 Trap 2
Subtotal
                                     0.98
                                     0.79
                                     0.10
                                     0.05
                                     1.61
                                     0.78
                                     0.55
                                     0.49
Exhaled VOC Trap 1
SUBTOTAL
                                     41.65
                                     2.65
                                     40.84
                                     1.70
                                     58.4e
                                     6.05
                                   69.27a,e
                                     2.45
Exhaled VOC Trap 2
Subtotal
                                     0.23
                                     0.21
                                     0.05
                                     0.02
                                     5.22d
                                      1.3
                                     1.26b
                                     0.99
Cage Rinse
24 h
                                     0.59
                                     0.34
                                     0.51
                                     0.11
                                     0.54
                                     0.08
                                     0.36
                                     0.11
NO Tube Contents
24 h
                                     0.92
                                     0.88
                                     0.81
                                     0.36
                                     1.39
                                     0.55
                                      0.6
                                     0.39
Adipose subcutaneous
24 h
                                     0.01
                                     0.01
                                     0.01
                                     0.00
                                     0.00
                                     0.00
                                     0.01
                                     0.00
Adip (Abdominal)
24 h
                                     0.01
                                     0.01
                                     0.02
                                     0.02
                                     0.01
                                     0.00
                                     0.01
                                     0.00
Muscle Gastrocnemius
24 h
                                     0.01
                                     0.00
                                     0.01
                                     0.00
                                     0.01d
                                     0.00
                                     0.01c
                                     0.00
Skin (neck)
24 h
                                     0.02
                                     0.01
                                     0.01
                                     0.01
                                     0.01
                                     0.00
                                     0.01
                                     0.00
Blood
24 h
                                     0.08
                                     0.01
                                     0.11
                                     0.04
                                     0.05d
                                     0.00
                                     0.05
                                     0.01
Spleen
24 h
                                     0.04
                                     0.00
                                     0.05b
                                     0.00
                                     0.03e
                                     0.00
                                     0.03e
                                     0.01
Liver
24 h
                                     1.27
                                     0.11
                                     1.31
                                     0.18
                                     1.04
                                     0.28
                                     0.98c
                                     0.16
Kidney
24 h
                                     0.19
                                     0.02
                                     0.18
                                     0.01
                                     0.12d
                                     0.02
                                     0.09e
                                     0.02
Heart
24 h
                                     0.03
                                     0.00
                                     0.04a
                                     0.00
                                     0.02e
                                     0.00
                                     0.02d
                                     0.01
Lung
24 h
                                     0.10
                                     0.01
                                     0.14b
                                     0.01
                                     0.07d
                                     0.01
                                     0.08e
                                     0.02
Brain
24 h
                                     0.05
                                     0.01
                                     0.07a
                                     0.01
                                     0.03d
                                     0.00
                                     0.02e
                                     0.00
Femur
24 h
                                     0.02
                                     0.00
                                     0.03a
                                     0.00
                                     0.01c
                                     0.00
                                    0.01a,e
                                     0.00
Testes/Ovaries &Uterus
24 h
                                     0.10
                                     0.01
                                     0.04
                                     0.00
                                     0.05e
                                     0.00
                                     0.03
                                     0.01
Stomach
24 h
                                     0.08
                                     0.01
                                     0.09
                                     0.01
                                     0.05d
                                     0.01
                                     0.05e
                                     0.01
Small Intestine
24 h
                                     0.54
                                     0.09
                                     0.57
                                     0.09
                                     0.38c
                                     0.08
                                     0.31d
                                     0.02
Cecum+Lg Int+Rect
24 h
                                     0.20
                                     0.03
                                     0.22
                                     0.02
                                     0.13c
                                     0.03
                                     0.11d
                                     0.00
Stomach Contents
24 h
                                     0.00
                                     0.00
                                     0.01
                                     0.00
                                     0.00
                                     0.00
                                     0.01
                                     0.00
Small Intestine Cont
24 h
                                     0.23
                                     0.06
                                     0.34a
                                     0.05
                                     0.21
                                     0.04
                                     0.18d
                                     0.05
Lg Int + Cecum Cont
24 h
                                     0.32
                                     0.03
                                     0.35
                                     0.08
                                      0.3
                                     0.06
                                     0.25
                                     0.02
Carcass Digest
24 h
                                     7.89
                                     0.75
                                     8.15
                                     0.59
                                     5.15d
                                     0.69
                                     4.13e
                                     0.79

Subtotal
                                     12.71
                                     2.06
                                     13.07
                                     0.94
                                     8.21
                                     1.16
                                     6.74
                                     1.08

Total
                                    100.00
                                     0.00
                                      100
                                     0.00
                                      100
                                     0.00
                                      100
                                     0.00

a Significantly different from Male at the equivalent concentration P<0.05
b Significantly different from Male at the equivalent concentration P<0.01
c Significantly different from 600 ppm for the same gender P<0.05
d Significantly different from 600 ppm for the same gender P<0.01
e Significantly different from 600 ppm for the same gender P<0.001

Table 37.  Recovery of DIPE in Excreta and Tissues Following Inhalation Exposure of Male and Female F344 Rats to a Single or Repeated Exposure to 3600 ppm DIPE

                                   3600 ppm
                                   Group 3
                                   Male Rats
                                   3600 ppm
                                   Group 4
                                  Female Rats
                           3600 ppm Repeat Group 5
                                   Male Rats
                                3600 ppm Repeat
                                   Group 6
                                  Female Rats
                                    Sample
                                  Time point
                                     Mean
                                      SD
                                     Mean
                                      SD
                                     Mean
                                      SD
                                     Mean
                                      SD
Urine
                                                                       Subtotal
                                     4.21
                                     0.76
                                     3.55
                                     0.26
                                     8.54c
                                     0.98
                                                                        6.84c,d
                                                                           0.51
Feces
                                                                       Subtotal
                                     0.44
                                     0.08
                                     0.28
                                     0.12
                                     0.93b
                                     0.14
                                                                          0.82a
                                                                           0.31
CO2 Trap 1
                                                                       Subtotal
                                     20.51
                                     4.39
                                     17.74
                                     1.51
                                     24.0
                                     11.1
                                                                          25.1c
                                                                           1.24
CO2 Trap 2
                                                                       Subtotal
                                     1.61
                                     0.78
                                     0.55
                                     0.49
                                     9.78
                                     10.4
                                                                           1.27
                                                                           1.33
Exhaled VOC Trap 1
                                                                       Subtotal
                                     58.4
                                     6.05
                                    69.27d
                                     2.45
                                     41.9b
                                     2.08
                                                                        49.0c,d
                                                                           4.13
Exhaled VOC Trap 2
                                                                       Subtotal
                                     5.22
                                      1.3
                                     1.26e
                                     0.99
                                     3.15a
                                     0.83
                                                                           3.82
                                                                           2.26
Cage Rinse
                                     24 h
                                     0.54
                                     0.08
                                     0.36
                                     0.11
                                     0.66
                                     0.25
                                                                           0.50
                                                                           0.16
NO Tube Contents
                                      0 m
                                     1.39
                                     0.55
                                      0.6
                                     0.39
                                     0.30a
                                     0.31
                                                                           0.61
                                                                           0.13
Adipose subcutaneous
                                     24 h
                                     0.00
                                     0.00
                                     0.01
                                     0.00
                                     0.04a
                                     0.02
                                                                          0.04c
                                                                           0.01
Adip (Abdominal)
                                     24 h
                                     0.01
                                     0.00
                                     0.01
                                     0.00
                                     0.04c
                                     0.01
                                                                           0.07
                                                                           0.04
Muscle Gastrocnemius
                                     24 h
                                     0.01
                                     0.00
                                     0.01
                                     0.00
                                     0.01
                                     0.01
                                                                           0.01
                                                                           0.00
Skin (neck)
                                     24 h
                                     0.01
                                     0.00
                                     0.01
                                     0.00
                                     0.01
                                     0.01
                                                                           0.02
                                                                           0.01
Blood
                                     24 h
                                     0.05
                                     0.00
                                     0.05
                                     0.01
                                     0.07a
                                     0.01
                                                                          0.10b
                                                                           0.02
Spleen
                                     24 h
                                     0.03
                                     0.00
                                     0.03
                                     0.01
                                     0.03a
                                     0.01
                                                                          0.05a
                                                                           0.01
Liver
                                     24 h
                                     1.04
                                     0.28
                                     0.98
                                     0.16
                                     1.88b
                                     0.24
                                                                          1.58b
                                                                           0.25
Kidney
                                     24 h
                                     0.12
                                     0.02
                                     0.09
                                     0.02
                                     0.16a
                                     0.02
                                                                          0.17a
                                                                           0.04
Heart
                                     24 h
                                     0.02
                                     0.00
                                     0.02
                                     0.01
                                     0.03
                                     0.01
                                                                           0.04
                                                                           0.01
Lung
                                     24 h
                                     0.07
                                     0.01
                                     0.08
                                     0.02
                                     0.10c
                                     0.01
                                                                          0.12a
                                                                           0.02
Brain
                                     24 h
                                     0.03
                                     0.00
                                     0.02
                                     0.00
                                     0.03
                                     0.01
                                                                           0.03
                                                                           0.01
Femur
                                     24 h
                                     0.01
                                     0.00
                                     0.01d
                                     0.00
                                     0.02a
                                     0.01
                                                                          0.02a
                                                                           0.01
Testes/Ovaries &Uterus
                                     24 h
                                     0.05
                                     0.00
                                     0.03
                                     0.01
                                     0.06a
                                     0.00
                                                                           0.03
                                                                           0.02
Stomach
                                     24 h
                                     0.05
                                     0.01
                                     0.05
                                     0.01
                                     0.07b
                                     0.01
                                                                          0.08b
                                                                           0.01
Small Intestine
                                     24 h
                                     0.38
                                     0.08
                                     0.31
                                     0.02
                                     0.47
                                     0.04
                                                                          0.51a
                                                                           0.11
Cecum+Lg Int+Rect
                                     24 h
                                     0.13
                                     0.03
                                     0.11
                                     0.00
                                     0.18a
                                     0.01
                                                                          0.18a
                                                                           0.03
Stomach Contents
                                     24 h
                                     0.00
                                     0.00
                                     0.01
                                     0.00
                                     0.01
                                     0.01
                                                                          0.01c
                                                                           0.00
Small Intestine Cont
                                     24 h
                                     0.21
                                     0.04
                                     0.18
                                     0.05
                                     0.24
                                     0.06
                                                                          0.27a
                                                                           0.02
Lg Int + Cecum Cont
                                     24 h
                                      0.3
                                     0.06
                                     0.25
                                     0.02
                                     0.30
                                     0.05
                                                                           0.37
                                                                           0.11
Carcass Digest
                                     24 h
                                     5.15
                                     0.69
                                     4.13
                                     0.79
                                     7.10b
                                     0.64
                                                                          8.18b
                                                                           1.26

                                   Subtotal
                                     8.21
                                     1.16
                                     6.74
                                     1.08
                                     11.5
                                     0.89
                                                                           12.3
                                                                           1.73

                                     Total
                                      100
                                     0.00
                                      100
                                     0.00
                                     100.
                                     0.05
                                                                            100
                                                                           0.06

a Significantly different from  a single exposure P<0.05
b Significantly different from a single exposure P<0.01
c Significantly different from a single exposure P<0.001
d Significantly different from male P<0.05
e Significantly different from male P<0.01
f Significantly different from male P<0.001

Table 38.  Concentration of DIPE equivalents (ug/g) in Tissues Following Inhalation Exposure of Male and Female F344 Rats to 600 ppm or 3600 ppm

                                   600 ppm
                                   Group 1
                                   Male Rats
                                   600 ppm
                                   Group 2
                                  Female Rats
                                   3600 ppm
                                   Group 3
                                   Male Rats
                                   3600 ppm
                                   Group 4
                                  Female Rats
Sample
                                     Mean
                                      SD
                                     Mean
                                      SD
                                     Mean
                                      SD
                                     MEAN
                                      SD
Adipose subcutaneous
                                     8.21
                                     5.77
                                     7.59
                                     1.97
                                     14.4
                                     4.59
                                     13.2
                                     4.33
Adip (Abdominal)
                                     13.5
                                     3.93
                                     12.6
                                      9.7
                                     25.3
                                     15.3
                                     24.6
                                     14.4
Muscle Gastrocnemius
                                     5.13
                                     0.393
                                     5.27
                                     0.557
                                     9.93c
                                     1.14
                                    7.22A,D
                                     1.14
Skin (neck)
                                     13.9
                                     4.57
                                     8.80
                                     2.26
                                     34.0b
                                      9.2
                                    18.8A,D
                                     6.84
Blood
                                     5.83
                                     0.313
                                     6.13
                                     0.484
                                     14.8c
                                     0.943
                                    11.4C,E
                                     1.15
Spleen
                                      16
                                     1.06
                                     17.0
                                     1.22
                                     40.8c
                                     3.04
                                    34.0C,E
                                     1.73
Liver
                                     25.5
                                     1.51
                                     28.0
                                     3.51
                                     79.2b
                                     15.1
                                     71.6C
                                      12
Kidney
                                     20.2
                                     2.41
                                     17.0
                                     1.25
                                     49.2c
                                     4.74
                                    35.4C,E
                                     3.06
Heart
                                     7.25
                                     0.672
                                     7.92
                                     0.88
                                     17.5c
                                     1.75
                                     15.3C
                                     2.17
Lung
                                     17.5
                                      2.5
                                     17.9
                                     2.13
                                     48.8c
                                     6.05
                                     43.0C
                                     4.79
Brain
                                      4.6
                                     0.589
                                     4.01
                                     0.47
                                     9.16c
                                     0.831
                                    5.62B,F
                                     0.573
Femur
                                     11.3
                                     0.983
                                     11.6
                                     0.918
                                     21.8a
                                     4.49
                                     17.4B
                                     2.52
Testes/Ovaries &Uterus
                                     6.33
                                     0.519
                                     13.4
                                      2.2
                                     13.4c
                                      1.3
                                     26.1B
                                     4.66
Stomach
                                     11.9
                                     0.403
                                     12.2
                                     1.16
                                     32.6c
                                     3.23
                                    27.1C,D
                                     1.47
Small Intestine
                                      25
                                     2.55
                                     24.3
                                     2.18
                                     70.3b
                                     8.83
                                    53.8C,D
                                     3.41
Cecum+Lg Int+Rect
                                      18
                                     1.38
                                     16.7
                                     0.866
                                     46.9c
                                     3.76
                                    32.7C,F
                                     2.51
Stomach Contents
                                     1.58
                                     1.58
                                     2.02
                                     1.93
                                     3.43
                                     4.15
                                     2.78D
                                     0.776
Small Intestine Cont
                                     15.2
                                     3.68
                                     17.1
                                     3.53
                                     59.5a
                                     24.3
                                     34.6C
                                     3.82
Lg Int + Cecum Cont
                                      9.4
                                     0.49
                                     9.32
                                     1.76
                                     33.7c
                                     3.09
                                    20.7C,F
                                     2.24
Carcass Digest
                                     8.42
                                     0.857
                                     8.57
                                     0.489
                                     20.4c
                                     2.48
                                    15.4B,D
                                     2.28

a Significantly different from  a 600 ppm exposure P<0.05
b Significantly different from a 600 ppm exposure P<0.01
c Significantly different from a 600 ppm exposure P<0.001
d Significantly different from male P<0.05
e Significantly different from male P<0.01
f Significantly different from male P<0.001

Table 39.  Concentration of DIPE equivalents (ug/g) in Tissues Following Inhalation Exposure of Male and Female F344 Rats to single or repeat exposures to 3600 ppm DIPE

                                   3600 ppm
                                   Group 3
                                   Male Rats
                                   3600 ppm
                                   Group 4
                                  Female Rats
                                   3600 ppm
                                   Group 5
                                   Male Rats
                                   3600 ppm
                                   Group 6
                                  Female Rats
Sample
                                     Mean
                                      SD
                                     Mean
                                      SD
                                     Mean
                                      SD
                                     Mean
                                      SD
Adipose subcutaneous
                                     14.4
                                     4.59
                                     13.2
                                     4.33
                                                                           172b
                                                                           33.9
                                                                         145.0c
                                                                           47.8
Adip (Abdominal)
                                     25.3
                                     15.3
                                     24.6
                                     14.4
                                                                           301c
                                                                           73.3
                                                                            330
                                                                            210
Muscle Gastrocnemius
                                     9.93
                                     1.14
                                     7.22
                                     1.14
                                                                          19.2c
                                                                            0.5
                                                                        12.5c,d
                                                                            2.5
Skin (neck)
                                     34.0
                                      9.2
                                     18.8
                                     6.84
                                                                           61.1
                                                                           26.6
                                                                           52.3
                                                                           31.2
Blood
                                     14.8
                                     0.943
                                     11.4
                                     1.15
                                                                          32.6c
                                                                            3.4
                                                                        25.2c,d
                                                                            2.3
Spleen
                                     40.8
                                     3.04
                                     34.0
                                     1.73
                                                                          91.9c
                                                                            5.4
                                                                        72.1c,d
                                                                           11.7
Liver
                                     79.2
                                     15.1
                                     71.6
                                      12
                                                                           209c
                                                                           25.7
                                                                           160c
                                                                           49.7
Kidney
                                     49.2
                                     4.74
                                     35.4
                                     3.06
                                                                           107c
                                                                           16.3
                                                                          87.4c
                                                                           28.1
Heart
                                     17.5
                                     1.75
                                     15.3
                                     2.17
                                                                          35.7c
                                                                            4.2
                                                                          37.7c
                                                                           13.5
Lung
                                     48.8
                                     6.05
                                     43.0
                                     4.79
                                                                           111c
                                                                            4.8
                                                                          92.8c
                                                                           28.7
Brain
                                     9.16
                                     0.831
                                     5.62
                                     0.573
                                                                          15.6c
                                                                            1.6
                                                                        10.0c,e
                                                                            2.3
Femur
                                     21.8
                                     4.49
                                     17.4
                                     2.52
                                                                          52.9c
                                                                            6.4
                                                                          32.6d
                                                                           11.1
Testes/Ovaries &Uterus
                                     13.4
                                      1.3
                                     26.1
                                     4.66
                                                                          24.2c
                                                                            2.2
                                                                          59.7a
                                                                           19.9
Stomach
                                     32.6
                                     3.23
                                     27.1
                                     1.47
                                                                          69.0c
                                                                            8.9
                                                                           48.6
                                                                           21.9
Small Intestine
                                     70.3
                                     8.83
                                     53.8
                                     3.41
                                                                           150c
                                                                           10.5
                                                                           124a
                                                                           36.1
Cecum+Lg Int+Rect
                                     46.9
                                     3.76
                                     32.7
                                     2.51
                                                                          97.3c
                                                                            7.6
                                                                          80.5a
                                                                           23.8
Stomach Contents
                                     3.43
                                     4.15
                                     2.78
                                     0.776
                                                                           10.6
                                                                            5.3
                                                                            4.3
                                                                            1.6
Small Intestine Cont
                                     59.5
                                     24.3
                                     34.6
                                     3.82
                                                                           71.1
                                                                           14.7
                                                                          56.8a
                                                                           14.4
Lg Int + Cecum Cont
                                     33.7
                                     3.09
                                     20.7
                                     2.24
                                                                          43.0a
                                                                            4.0
                                                                            139
                                                                            133
Carcass Digest
                                     20.4
                                     2.48
                                     15.4
                                     2.28
                                                                          52.7c
                                                                            4.2
                                                                          44.3a
                                                                           12.1

a Significantly different from  a single exposure P<0.05
b Significantly different from a single exposure P<0.01
c Significantly different from a single exposure P<0.001
d Significantly different from male P<0.05
e Significantly different from male P<0.01
f Significantly different from male P<0.001

Table 40.  Recovery of DIPE Following Gavage Administration to Male and Female F344 Rats of 50 or 200 mg/kg DIPE

                                   50 mg/kg
                                   Group 7
                                   Male Rats
                         50 mg/kg  Group 8 Female Rats
                              200 mg/kg Group 9
                                   Male Rats
                        200 mg/kg Group 10 Female Rats
Sample
                                  Time point
                                     Mean
                                      SD
                                     Mean
                                      SD
                                     Mean
                                      SD
                                     Mean
                                      SD
Urine
                                   Subtotal
                                     2.47
                                     0.24
                                     2.22
                                     0.22
                                     1.57d
                                     0.54
                                     1.55e
                                     0.09
Feces
                                   Subtotal
                                     0.20
                                     0.05
                                     0.11a
                                     0.05
                                     0.16
                                     0.05
                                     0.10
                                     0.04
CO2 Trap 1
                                   Subtotal
                                     16.8
                                     1.30
                                     18.1
                                     0.93
                                     9.00f
                                     0.53
                                     8.81f
                                     2.27
CO2 Trap 2
                                   Subtotal
                                     0.74
                                     0.14
                                     0.14
                                     0.12
                                     0.46
                                     0.22
                                     0.02a
                                     0.04
Exhaled VOC Trap 1
                                   Subtotal
                                     52.3
                                     3.60
                                     55.9
                                     1.35
                                     56.4
                                     7.50
                                     61.4e
                                     1.55
Exhaled VOC Trap 2
                                   Subtotal
                                     0.11
                                     0.09
                                     0.02
                                     0.01
                                     0.57
                                     0.47
                                     0.03
                                     0.01
Cage Rinse
                                     24 h
                                     0.19
                                     0.02
                                     0.37
                                     0.13
                                     0.32
                                     0.32
                                     0.17
                                     0.03
Adipose subcutaneous
                                     24 h
                                     0.01
                                     0.01
                                     0.01
                                     0.00
                                     0.00d
                                     0.00
                                     0.00
                                     0.00
Adip (Abdominal)
                                     24 h
                                     0.01
                                     0.00
                                     0.01
                                     0.00
                                     0.00
                                     0.00
                                     0.00
                                     0.00
Muscle Gastrocnemius
                                     24 h
                                     0.00
                                     0.00
                                     0.00
                                     0.00
                                     0.00f
                                     0.00
                                     0.00f
                                     0.00
Skin (neck)
                                     24 h
                                     0.02
                                     0.01
                                     0.02
                                     0.00
                                     0.01e
                                     0.00
                                     0.01d
                                     0.01
Blood
                                     24 h
                                     0.04
                                     0.00
                                     0.05a
                                     0.00
                                     0.02c
                                     0.00
                                    0.03a,f
                                     0.00
Spleen
                                     24 h
                                     0.02
                                     0.00
                                     0.03
                                     0.00
                                     0.01e
                                     0.00
                                    0.02b,e
                                     0.00
Liver
                                     24 h
                                     0.62
                                     0.11
                                     0.57
                                     0.05
                                     0.32e
                                     0.03
                                     0.35f
                                     0.02
Kidney
                                     24 h
                                     0.09
                                     0.01
                                     0.08a
                                     0.01
                                     0.05e
                                     0.00
                                    0.05a,f
                                     0.00
Heart
                                     24 h
                                     0.01
                                     0.00
                                     0.02
                                     0.00
                                     0.01f
                                     0.00
                                     0.01d
                                     0.00
Lung
                                     24 h
                                     0.05
                                     0.01
                                     0.06
                                     0.01
                                     0.03e
                                     0.00
                                    0.04c,d
                                     0.00
Brain
                                     24 h
                                     0.02
                                     0.00
                                     0.02
                                     0.00
                                     0.01f
                                     0.00
                                     0.01f
                                     0.00
Femur
                                     24 h
                                     0.01
                                     0.00
                                     0.01
                                     0.00
                                     0.01e
                                     0.00
                                     0.01c
                                     0.00
Testes/Ovaries &Uterus
                                     24 h
                                     0.04
                                     0.00
                                     0.03
                                     0.01
                                     0.02f
                                     0.00
                                     0.03
                                     0.01
Stomach
                                     24 h
                                     0.04
                                     0.01
                                     0.04
                                     0.00
                                     0.02e
                                     0.00
                                     0.02e
                                     0.01
Small Intestine
                                     24 h
                                     0.28
                                     0.06
                                     0.25
                                     0.02
                                     0.13e
                                     0.02
                                     0.15f
                                     0.01
Cecum+Lg Int+Rect
                                     24 h
                                     0.13
                                     0.01
                                     0.18
                                     0.01
                                     0.08f
                                     0.00
                                     0.11f
                                     0.00
Stomach Contents
                                     24 h
                                     0.01
                                     0.00
                                     0.01
                                     0.00
                                     0.00
                                     0.00
                                     0.01
                                     0.01
Small Intestine Cont
                                     24 h
                                     0.14
                                     0.01a
                                     0.18
                                     0.02
                                     0.11
                                     0.02
                                     0.12e
                                     0.01
Lg Int + Cecum Cont
                                     24 h
                                     0.10
                                     0.02b
                                     0.09
                                     0.01
                                     0.05e
                                     0.01
                                    0.05c,f
                                     0.00
                                Carcass Digest
                                     24 h
                                     4.12
                                     0.43
                                     3.30a
                                     0.29
                                     2.03e
                                     0.07
                                    1.81b,e
                                     0.07

                                   Subtotal
                                     5.96
                                     0.60
                                     5.33
                                     0.47
                                     3.24
                                     0.27
                                     2.99
                                     0.08

                                     Total
                                     78.6
                                     3.05
                                     81.8
                                      1.3
                                     71.4
                                     8.12
                                     74.9
                                     2.99

a Significantly different from Male at the same dose P<0.05
b Significantly different from Male at the same dose P<0.01
c Significantly different from Male at the same dose P<0.01
d Significantly different from 50 mg/kg for the same gender P<0.05
e Significantly different from 50 mg/kg for the same gender P<0.01
f Significantly different from 50 mg/kg for the same gender P<0.001

Table 41.  Concentration of DIPE equivalents (ug/g) in Tissues Following Gavage Administration to Male and Female F344 Rats of 50 or 200 mg/kg DIPE

                                   50 mg/kg
                                    Group 7
                                   Male Rats
                                   50 mg/kg
                                   Group 8
                                  Female Rats
                                  200 mg/kg
                                   Group 9
                                   Male Rats
                                  200 mg/kg
                                   Group 10
                                  Female Rats
Sample
                                     Mean
                                      SD
                                     MEAN
                                      SD
                                     Mean
                                      SD
                                     Mean
                                      SD
Adipose subcutaneous
                                     2.33
                                     1.21
                                     2.40
                                     0.83
                                     3.45
                                     0.90
                                     3.95
                                     1.24
Adip (Abdominal)
                                     3.24
                                     2.24
                                     2.85
                                     1.60
                                     5.88
                                     1.68
                                     4.25
                                     1.88
Muscle Gastrocnemius
                                     1.58
                                     0.25
                                     1.05b
                                     0.09
                                     2.78e
                                     0.32
                                     2.05f
                                     0.22
Skin (neck)
                                     5.88
                                     0.61
                                     5.32
                                     0.66
                                     11.0f
                                     0.73
                                     9.77
                                     3.32
Blood
                                     1.84
                                     0.14
                                     1.64
                                     0.14
                                     3.81f
                                     0.13
                                     3.68f
                                     0.13
Spleen
                                     4.86
                                     0.41
                                     5.10
                                     0.61
                                     10.6f
                                     0.74
                                     11.6f
                                     0.53
Liver
                                     6.94
                                     0.88
                                     7.52
                                     0.52
                                     15.4f
                                     1.42
                                     18.5f
                                     1.24
Kidney
                                     5.98
                                     0.49
                                     5.36
                                     0.34
                                     13.1f
                                     1.34
                                     11.9f
                                     0.35
Heart
                                     2.11
                                     0.15
                                     2.33
                                     0.37
                                     4.37e
                                     0.70
                                     5.28f
                                     0.57
Lung
                                     5.38
                                     0.60
                                     5.62
                                     0.42
                                     11.6f
                                     1.28
                                     12.7f
                                     0.95
Brain
                                     1.00
                                     0.08
                                     0.87
                                     0.09
                                     2.07f
                                     0.18
                                     1.83f
                                     0.16
Femur
                                     3.22
                                     0.58
                                     2.52
                                     0.54
                                     6.26e
                                     0.85
                                     6.00f
                                     0.46
Testes/Ovaries &Uterus
                                     1.53
                                     0.12
                                     4.08
                                     1.22
                                     3.16f
                                     0.25
                                    10.30e
                                     2.39
Stomach
                                     4.11
                                     0.66
                                     4.14
                                     0.28
                                     8.98f
                                     0.77
                                     7.76f
                                     4.08
Small Intestine
                                     8.30
                                     1.13
                                     8.74
                                     0.32
                                     17.8e
                                     3.12
                                     20.3f
                                     0.50
Cecum+Lg Int+Rect
                                     5.36
                                     0.91
                                     5.02
                                     0.46
                                     11.9f
                                     0.85
                                     11.2f
                                     1.16
Stomach Contents
                                     0.31
                                     0.08
                                     0.58
                                     0.30
                                     1.42
                                     0.76
                                     4.21
                                     4.09
Small Intestine Cont
                                     4.04
                                     0.46
                                     5.42a
                                     0.68
                                     13.2d
                                     3.74
                                     14.7f
                                     0.90
Lg Int + Cecum Cont
                                     1.91
                                     0.16
                                     2.04
                                     0.28
                                     5.04e
                                     0.87
                                     5.29f
                                     0.17
Carcass Digest
                                     2.54
                                     0.27
                                     2.08a
                                     0.22
                                     5.15f
                                     0.22
                                     4.51f
                                     0.18

a Significantly different from Male at the same dose P<0.05
b Significantly different from Male at the same dose P<0.01
c Significantly different from Male at the same dose P<0.01
d Significantly different from 50 mg/kg for the same gender P<0.05
e Significantly different from 50 mg/kg for the same gender P<0.01
f Significantly different from 50 mg/kg for the same gender P<0.001

Figure 1.  Cumulative Excretion of Radioactivity in Urine and Feces, CO2 and Exhaled VOC Traps for Male (Group 1) and Female (Group 2) Rats Exposed to 600 ppm [2-[14]C]DIPE

Figure 2.  Cumulative Excretion of Radioactivity in Urine and Feces, CO2 and Exhaled VOC Traps for Male (Group 3) and Female (Group 4) Rats Exposed to 3600 ppm [2-14C]DIPE

Figure 3.  Cumulative Excretion of Radioactivity in Urine and Feces, CO2 and Exhaled VOC Traps for Male (Group 5) and Female (Group 6) Rats Exposed to 3600 ppm DIPE for 4 Days Followed by Exposure to 3600 ppm [2-14C]DIPE on Day 5

Figure 4.  Cumulative Excretion of Radioactivity in Urine and Feces, CO2 and Exhaled VOC Traps for Male (Group 7) and Female (Group 8) Rats Administered 50 mg/kg [2-14C]DIPE by Gavage

Figure 5.  Cumulative Excretion of Radioactivity in Urine and Feces, CO2 and Exhaled VOC Traps for Male (Group 9) and Female (Group 10) Rats Administered 200 mg/kg [2-14C]DIPE by Gavage

Figure 6.  Blood Concentrations (Mean +- SD) of DIPE in Male and Female Rats Exposed to 600 ppm DIPE for 6 hr.

Figure 7.  Blood Concentrations (Mean +- SD) of Isopropanol in Male and Female Rats Exposed to 600 ppm DIPE for 6 hr.

Figure 8.  Blood Concentrations of Acetone (Mean +- SD) in Male and Female Rats Exposed to 600 ppm DIPE for 6 hr.

Figure 9.  Blood Concentrations of DIPE (Mean +- SD) in Male and Female Rats Exposed to 3600 ppm DIPE for 6 hr.

Figure 10.  Blood Concentrations of Isopropanol (Mean +- SD) in Male and Female Rats Exposed to 3600 ppm DIPE for 6 hr.

Figure 11.  Blood Concentrations of Acetone (Mean +- SD) in Male and Female Rats Exposed to 3600 ppm DIPE for 6 hr.

Appendix A
Approved Study Protocol, Amendments, and Deviations

        RTI Protocol No. RTI-1117 (RTI Project No. 0221608.002 and .003)

--------------------------------------------------------------------------------

                     Deviations from the Approved Protocol
--------------------------------------------------------------------------------

The deviations listed below did not affect the results of the study.

Deviation  Shortened quarantine period for animals in Groups 5/6.
Reason for the Deviation  Due to shipping schedules and study execution schedules, the quarantine/isolation period was shortened to 3 days (from the 7 in the protocol).  The Sponsor was informed of the planned change and agreed with it, but there was insufficient time prior to animal arrival to ensure full signature of the protocol amendment in advance, so a deviation was written.

Deviation  Molecular weight for DIPE is 102.17, but protocol said 102.18.
Reason for the Deviation  The protocol stated MW 102.18, but the test article documentation and other sources (MSDS, Wikipedia) give the MW as 102.17.  The molecular weight of 102.17 was used in the study.

Deviation  Blood aliquots for LSS analysis were about 200 uL rather than `approximately 50 uL' as described in the protocol
Reason for the Deviation.  This change was made on verbal instruction from the SD.  The larger sample size allowed for better measurement of radioactivity in blood.

Deviation
Reason for the Deviation

Deviation

Reason for the Deviation

Deviation
Reason for the Deviation

.
Appendix B
Test Chemical Analysis Report

Appendix C

           Test Chemical Analysis Report:  2-[14]C Diisopropyl ether

Appendix D
Method Validation for Analysis of DIPE, Isopropanol and Acetone

Appendix E
 Inhalation Report

Appendix F
Pharmacokinetic Analysis

DIPE

Input File: Data - [A:\DIPEDEF3.XLS]
Sex=Female
EXP=600

Start Time: 21:08:50 05-03-2014
End Time:   21:08:51 05-03-2014

          WINNONLIN NONCOMPARTMENTAL ANALYSIS PROGRAM (V01.5A)
                          Core Version 29Oct97

 Listing of input commands

TITLE 1
RTI-1117 DIPE, Isopropanol and Acetone, 600 or 3600 pm exposure to DIPE for 6 ho
MODEL 200
DATE
TIME
NVARIABLES 6
NPOINTS 100
XNUMBER 1
YNUMBER 4
DTIME 0
NCONSTANTS 1
CONSTANTS 600
METHOD 2  'Linear trapezoidal
NCATRANS
MISSING 'Missing'
NOBSERVATIONS 14
DATA 'WINNLIN.DAT'
BEGIN
                                                         Date:   05/03/2014
                                                         Time:     21:08:50
RTI-1117 DIPE, Isopropanol and Acetone, 600 or 3600 pm exposure to DIPE for 6 ho

 WINNONLIN NONCOMPARTMENTAL ANALYSIS PROGRAM

         Noncompartmental Analysis for Extravascular Administration

             Linear Trapezoidal Rule Used to Compute AUC, AUMC

  X             Y          Pred.      Res.       AUC        AUMC      WEIGHT
 ----------------------------------------------------------------------------
  .0000         .0000                            .0000      .0000
  .8333E-01     3.083                            .1285      .1071E-01
  .1667         4.300                            .4361      .5127E-01
  .2500         6.671                            .8932      .1506
  .5000         7.625                            2.680      .8357
  1.000         8.769                            6.779      3.981
  2.000         11.92                            17.13      20.29
  4.000         13.11                            42.16      96.56
  6.000         14.95                            70.21      238.7
  6.250         5.310                            72.74      254.0
  6.500         3.402                            73.83      261.0
  7.000         1.872                            75.15      269.8
  7.330     *   1.186      1.149      .3679E-01  75.66      273.4      1.000
  8.000     *   .6759      .7049     -.2903E-01  76.28      278.1      1.000
  10.00     *   .1655      .1638      .1738E-02  77.12      285.1      1.000
 ----------------------------------------------------------------------------

 *) Starred values were included in estimation of Lambda_z.

 @) Note - the concentration at time zero (DTIME) was added for extrapolation purposes

 Dosing_time                        .0000
 Rsq                                .9986
 Rsq(adjusted)                      .9972
 Corr(x:y)                         -.9993
 Tlag                               .0000
 Tmax                              6.0000
 Cmax                             14.9502
 No._points_Lambda_z                3
 Tlast                            10.0000
 Clast                              .1655
 AUClast                          77.1214
 Lambda_z                           .7298
 Lambda_z_lower                    7.3300
 Lambda_z_upper                   10.0000
 t1/2_Lambda_z                      .9498
 AUCall                           77.1214
 AUCINF(observed)                 77.3483
 AUCINF(observed)/D                 .1289
 AUC_%Extrap(obs.)                  .2932
 Vz(observed)/F                   10.6295
 Cl(observed)/F                    7.7571
 AUCINF(predicted)                77.3459
 AUCINF(predicted)/D                .1289
 AUC_%Extrap(pred.)                 .2902
 Vz(predicted)/F                  10.6298
 Cl(predicted)/F                   7.7574
 AUMClast                        285.1465
 AUMCINF(observed)               287.7255
 AUMC_%Extrap(obs.)                 .8963
 AUMCINF(predicted)              287.6984
 AUMC_%Extrap(pred.)                .8870
 MRTlast                           3.6974
 MRTINF(observed)                  3.7199
 MRTINF(predicted)                 3.7196

 NORMAL ENDING

Input File: Data - [A:\DIPEDEF3.XLS]
Sex=Female
EXP=3600

Start Time: 21:08:51 05-03-2014
End Time:   21:08:53 05-03-2014

          WINNONLIN NONCOMPARTMENTAL ANALYSIS PROGRAM (V01.5A)
                          Core Version 29Oct97

 Listing of input commands

TITLE 1
RTI-1117 DIPE, Isopropanol and Acetone, 600 or 3600 pm exposure to DIPE for 6 ho
MODEL 200
DATE
TIME
NVARIABLES 6
NPOINTS 100
XNUMBER 1
YNUMBER 4
DTIME 0
NCONSTANTS 1
CONSTANTS 3600
METHOD 2  'Linear trapezoidal
NCATRANS
MISSING 'Missing'
NOBSERVATIONS 14
DATA 'WINNLIN.DAT'
BEGIN
                                                         Date:   05/03/2014
                                                         Time:     21:08:51
RTI-1117 DIPE, Isopropanol and Acetone, 600 or 3600 pm exposure to DIPE for 6 ho

 WINNONLIN NONCOMPARTMENTAL ANALYSIS PROGRAM

         Noncompartmental Analysis for Extravascular Administration

             Linear Trapezoidal Rule Used to Compute AUC, AUMC

  X             Y          Pred.      Res.       AUC        AUMC      WEIGHT
 ----------------------------------------------------------------------------
  .0000         .0000                            .0000      .0000
  .8333E-01     28.54                            1.189      .9911E-01
  .1667         31.39                            3.687      .4162
  .2500         50.57                            7.102      1.161
  .5000         43.39                            18.85      5.453
  1.000         54.52                            43.33      24.51
  2.000         52.70                            96.94      104.5
  4.000         63.34                            213.0      463.2
  6.000         77.25                            353.6      1180.
  6.250         29.51                            366.9      1261.
  6.500         18.99                            373.0      1300.
  7.000         9.682                            380.1      1347.
  7.330     *   6.025      5.967      .5862E-01  382.7      1366.      1.000
  8.000     *   3.898      3.950     -.5122E-01  386.1      1391.      1.000
  10.00     *   1.156      1.153      .3781E-02  391.1      1434.      1.000
 ----------------------------------------------------------------------------

 *) Starred values were included in estimation of Lambda_z.

 @) Note - the concentration at time zero (DTIME) was added for extrapolation purposes

 Dosing_time                        .0000
 Rsq                                .9998
 Rsq(adjusted)                      .9996
 Corr(x:y)                         -.9999
 Tlag                               .0000
 Tmax                              6.0000
 Cmax                             77.2485
 No._points_Lambda_z                3
 Tlast                            10.0000
 Clast                             1.1563
 AUClast                         391.1128
 Lambda_z                           .6158
 Lambda_z_lower                    7.3300
 Lambda_z_upper                   10.0000
 t1/2_Lambda_z                     1.1255
 AUCall                          391.1128
 AUCINF(observed)                392.9904
 AUCINF(observed)/D                 .1092
 AUC_%Extrap(obs.)                  .4778
 Vz(observed)/F                   14.8750
 Cl(observed)/F                    9.1605
 AUCINF(predicted)               392.9843
 AUCINF(predicted)/D                .1092
 AUC_%Extrap(pred.)                 .4762
 Vz(predicted)/F                  14.8752
 Cl(predicted)/F                   9.1607
 AUMClast                       1433.8177
 AUMCINF(observed)              1455.6426
 AUMC_%Extrap(obs.)                1.4993
 AUMCINF(predicted)             1455.5712
 AUMC_%Extrap(pred.)               1.4945
 MRTlast                           3.6660
 MRTINF(observed)                  3.7040
 MRTINF(predicted)                 3.7039

 NORMAL ENDING

Input File: Data - [A:\DIPEDEF3.XLS]
Sex=Male
EXP=600

Start Time: 21:08:53 05-03-2014
End Time:   21:08:54 05-03-2014

          WINNONLIN NONCOMPARTMENTAL ANALYSIS PROGRAM (V01.5A)
                          Core Version 29Oct97

 Listing of input commands

TITLE 1
RTI-1117 DIPE, Isopropanol and Acetone, 600 or 3600 pm exposure to DIPE for 6 ho
MODEL 200
DATE
TIME
NVARIABLES 6
NPOINTS 100
XNUMBER 1
YNUMBER 4
DTIME 0
NCONSTANTS 1
CONSTANTS 600
METHOD 2  'Linear trapezoidal
NCATRANS
MISSING 'Missing'
NOBSERVATIONS 14
DATA 'WINNLIN.DAT'
BEGIN

                                                         Date:   05/03/2014
                                                         Time:     21:08:53
RTI-1117 DIPE, Isopropanol and Acetone, 600 or 3600 pm exposure to DIPE for 6 ho

 WINNONLIN NONCOMPARTMENTAL ANALYSIS PROGRAM

         Noncompartmental Analysis for Extravascular Administration

             Linear Trapezoidal Rule Used to Compute AUC, AUMC

  X             Y          Pred.      Res.       AUC        AUMC      WEIGHT
 ----------------------------------------------------------------------------
  .0000         .0000                            .0000      .0000
  .8333E-01     5.674                            .2364      .1970E-01
  .1667         7.543                            .7871      .9178E-01
  .2500         8.859                            1.471      .2364
  .5000         9.666                            3.786      1.117
  1.000         11.69                            9.124      5.248
  2.000         13.23                            21.58      24.32
  4.000         12.79                            47.61      102.0
  6.000         12.95                            73.35      230.8
  6.250         3.721                            75.44      243.5
  6.500         2.365                            76.20      248.3
  7.000         1.116                            77.07      254.1
  7.330     *   .7812      .7383      .4293E-01  77.38      256.3      1.000
  8.000     *   .4564      .4922     -.3577E-01  77.80      259.5      1.000
  10.00     *   .1495      .1467      .2804E-02  78.40      264.6      1.000
 ----------------------------------------------------------------------------

 *) Starred values were included in estimation of Lambda_z.

 @) Note - the concentration at time zero (DTIME) was added for extrapolation purposes

 Dosing_time                        .0000
 Rsq                                .9935
 Rsq(adjusted)                      .9870
 Corr(x:y)                         -.9967
 Tlag                               .0000
 Tmax                              2.0000
 Cmax                             13.2301
 No._points_Lambda_z                3
 Tlast                            10.0000
 Clast                              .1495
 AUClast                          78.4021
 Lambda_z                           .6052
 Lambda_z_lower                    7.3300
 Lambda_z_upper                   10.0000
 t1/2_Lambda_z                     1.1453
 AUCall                           78.4021
 AUCINF(observed)                 78.6491
 AUCINF(observed)/D                 .1311
 AUC_%Extrap(obs.)                  .3141
 Vz(observed)/F                   12.6050
 Cl(observed)/F                    7.6288
 AUCINF(predicted)                78.6445
 AUCINF(predicted)/D                .1311
 AUC_%Extrap(pred.)                 .3082
 Vz(predicted)/F                  12.6058
 Cl(predicted)/F                   7.6293
 AUMClast                        264.6146
 AUMCINF(observed)               267.4930
 AUMC_%Extrap(obs.)                1.0760
 AUMCINF(predicted)              267.4390
 AUMC_%Extrap(pred.)               1.0561
 MRTlast                           3.3751
 MRTINF(observed)                  3.4011
 MRTINF(predicted)                 3.4006

 NORMAL ENDING

Input File: Data - [A:\DIPEDEF3.XLS]
Sex=Male
EXP=3600

Start Time: 21:08:54 05-03-2014
End Time:   21:08:55 05-03-2014

          WINNONLIN NONCOMPARTMENTAL ANALYSIS PROGRAM (V01.5A)
                          Core Version 29Oct97

 Listing of input commands

TITLE 1
RTI-1117 DIPE, Isopropanol and Acetone, 600 or 3600 pm exposure to DIPE for 6 ho
MODEL 200
DATE
TIME
NVARIABLES 6
NPOINTS 100
XNUMBER 1
YNUMBER 4
DTIME 0
NCONSTANTS 1
CONSTANTS 3600
METHOD 2  'Linear trapezoidal
NCATRANS
MISSING 'Missing'
NOBSERVATIONS 14
DATA 'WINNLIN.DAT'
BEGIN

                                                         Date:   05/03/2014
                                                         Time:     21:08:54
RTI-1117 DIPE, Isopropanol and Acetone, 600 or 3600 pm exposure to DIPE for 6 ho

 WINNONLIN NONCOMPARTMENTAL ANALYSIS PROGRAM

         Noncompartmental Analysis for Extravascular Administration

             Linear Trapezoidal Rule Used to Compute AUC, AUMC

  X             Y          Pred.      Res.       AUC        AUMC      WEIGHT
 ----------------------------------------------------------------------------
  .0000         .0000                            .0000      .0000
  .8333E-01     28.23                            1.176      .9801E-01
  .1667         39.85                            4.013      .4728
  .2500         35.52                            7.153      1.119
  .5000         60.95                            19.21      6.039
  1.000         66.12                            50.98      30.19
  2.000         66.79                            117.4      130.0
  4.000         65.22                            249.4      524.5
  6.000         70.20                            384.9      1207.
  6.250         22.56                            396.4      1277.
  6.500         13.82                            401.0      1306.
  7.000         7.227                            406.3      1341.
  7.330     *   4.077      4.390     -.3128      408.1      1354.      1.000
  8.000     *   3.080      2.791      .2894      410.5      1372.      1.000
  10.00     *   .7042      .7219     -.1766E-01  414.3      1404.      1.000
 ----------------------------------------------------------------------------

 *) Starred values were included in estimation of Lambda_z.

 @) Note - the concentration at time zero (DTIME) was added for extrapolation purposes

 Dosing_time                        .0000
 Rsq                                .9911
 Rsq(adjusted)                      .9822
 Corr(x:y)                         -.9955
 Tlag                               .0000
 Tmax                              6.0000
 Cmax                             70.1978
 No._points_Lambda_z                3
 Tlast                            10.0000
 Clast                              .7042
 AUClast                         414.3040
 Lambda_z                           .6761
 Lambda_z_lower                    7.3300
 Lambda_z_upper                   10.0000
 t1/2_Lambda_z                     1.0252
 AUCall                          414.3040
 AUCINF(observed)                415.3456
 AUCINF(observed)/D                 .1154
 AUC_%Extrap(obs.)                  .2508
 Vz(observed)/F                   12.8195
 Cl(observed)/F                    8.6675
 AUCINF(predicted)               415.3717
 AUCINF(predicted)/D                .1154
 AUC_%Extrap(pred.)                 .2570
 Vz(predicted)/F                  12.8187
 Cl(predicted)/F                   8.6669
 AUMClast                       1403.9874
 AUMCINF(observed)              1415.9433
 AUMC_%Extrap(obs.)                 .8444
 AUMCINF(predicted)             1416.2430
 AUMC_%Extrap(pred.)                .8654
 MRTlast                           3.3888
 MRTINF(observed)                  3.4091
 MRTINF(predicted)                 3.4096

 NORMAL ENDING

ACETONE

Input File: Data - [A:\DIPEDEF3.XLS]
Sex=Female
EXP=600

Start Time: 21:00:50 05-03-2014
End Time:   21:00:52 05-03-2014

          WINNONLIN NONCOMPARTMENTAL ANALYSIS PROGRAM (V01.5A)
                          Core Version 29Oct97

 Listing of input commands

TITLE 1
RTI-1117 DIPE, Isopropanol and Acetone, 600 or 3600 pm exposure to DIPE for 6 ho
MODEL 200
DATE
TIME
NVARIABLES 6
NPOINTS 100
XNUMBER 1
YNUMBER 5
DTIME 0
NCONSTANTS 1
CONSTANTS 600
METHOD 2  'Linear trapezoidal
NCATRANS
MISSING 'Missing'
NOBSERVATIONS 16
DATA 'WINNLIN.DAT'
BEGIN
                                                         Date:   05/03/2014
                                                         Time:     21:00:50
RTI-1117 DIPE, Isopropanol and Acetone, 600 or 3600 pm exposure to DIPE for 6 ho

 WINNONLIN NONCOMPARTMENTAL ANALYSIS PROGRAM

         Noncompartmental Analysis for Extravascular Administration

             Linear Trapezoidal Rule Used to Compute AUC, AUMC

  X             Y          Pred.      Res.       AUC        AUMC      WEIGHT
 ----------------------------------------------------------------------------
  .0000         .0000                            .0000      .0000
  .8333E-01     4.965                            .2069      .1724E-01
  .1667         5.608                            .6475      .7343E-01
  .2500         6.533                            1.153      .1804
  .5000         12.07                            3.478      1.139
  1.000         20.51                            11.62      7.775
  2.000         30.07                            36.91      48.10
  4.000         65.11                            132.1      368.7
  6.000     *   95.77      104.3     -8.512      293.0      1204.      1.000
  6.250     *   100.5      98.46      2.016      317.5      1354.      1.000
  6.500     *   99.52      92.96      6.569      342.5      1513.      1.000
  7.000     *   96.71      82.86      13.85      391.6      1844.      1.000
  7.330     *   99.37      76.80      22.57      423.9      2076.      1.000
  8.000     *   79.63      65.83      13.80      483.9      2534.      1.000
  10.00     *   44.68      41.56      3.126      608.2      3618.      1.000
  16.00     *   2.642      10.45     -7.813      750.2      5085.      1.000
  24.00     *   3.334      1.660      1.674      774.1      5574.      1.000
 ----------------------------------------------------------------------------

 *) Starred values were included in estimation of Lambda_z.

 @) Note - the concentration at time zero (DTIME) was added for extrapolation purposes

 Dosing_time                        .0000
 Rsq                                .8606
 Rsq(adjusted)                      .8407
 Corr(x:y)                         -.9277
 Tlag                               .0000
 Tmax                              6.2500
 Cmax                            100.4741
 No._points_Lambda_z                9
 Tlast                            24.0000
 Clast                             3.3340
 AUClast                         774.0820
 Lambda_z                           .2300
 Lambda_z_lower                    6.0000
 Lambda_z_upper                   24.0000
 t1/2_Lambda_z                     3.0136
 AUCall                          774.0820
 AUCINF(observed)                788.5772
 AUCINF(observed)/D                1.3143
 AUC_%Extrap(obs.)                 1.8382
 Vz(observed)/F                    3.3080
 Cl(observed)/F                     .7609
 AUCINF(predicted)               781.3007
 AUCINF(predicted)/D               1.3022
 AUC_%Extrap(pred.)                 .9239
 Vz(predicted)/F                   3.3388
 Cl(predicted)/F                    .7680
 AUMClast                       5574.0910
 AUMCINF(observed)              5984.9976
 AUMC_%Extrap(obs.)                6.8656
 AUMCINF(predicted)             5778.7236
 AUMC_%Extrap(pred.)               3.5411
 MRTlast                           7.2009
 MRTINF(observed)                  7.5896
 MRTINF(predicted)                 7.3963

 NORMAL ENDING

Input File: Data - [A:\DIPEDEF3.XLS]
Sex=Female
EXP=3600

Start Time: 21:00:52 05-03-2014
End Time:   21:00:53 05-03-2014

          WINNONLIN NONCOMPARTMENTAL ANALYSIS PROGRAM (V01.5A)
                          Core Version 29Oct97

 Listing of input commands

TITLE 1
RTI-1117 DIPE, Isopropanol and Acetone, 600 or 3600 pm exposure to DIPE for 6 ho
MODEL 200
DATE
TIME
NVARIABLES 6
NPOINTS 100
XNUMBER 1
YNUMBER 5
DTIME 0
NCONSTANTS 1
CONSTANTS 3600
METHOD 2  'Linear trapezoidal
NCATRANS
MISSING 'Missing'
NOBSERVATIONS 16
DATA 'WINNLIN.DAT'
BEGIN
                                                         Date:   05/03/2014
                                                         Time:     21:00:52
RTI-1117 DIPE, Isopropanol and Acetone, 600 or 3600 pm exposure to DIPE for 6 ho

 WINNONLIN NONCOMPARTMENTAL ANALYSIS PROGRAM

         Noncompartmental Analysis for Extravascular Administration

             Linear Trapezoidal Rule Used to Compute AUC, AUMC

  X             Y          Pred.      Res.       AUC        AUMC      WEIGHT
 ----------------------------------------------------------------------------
  .0000         .0000                            .0000      .0000
  .8333E-01     4.209                            .1754      .1462E-01
  .1667         5.357                            .5740      .6643E-01
  .2500         8.750                            1.162      .1948
  .5000         11.93                            3.747      1.214
  1.000         23.05                            12.49      8.469
  2.000         44.40                            46.22      64.39
  4.000         87.33                            177.9      502.5
  6.000         128.7                            394.0      1624.
  6.250     *   142.1      168.1     -26.00      427.9      1832.      1.000
  6.500     *   149.6      158.7     -9.170      464.3      2064.      1.000
  7.000     *   154.1      141.5      12.62      540.2      2577.      1.000
  7.330     *   134.8      131.2      3.658      587.9      2918.      1.000
  8.000     *   132.5      112.4      20.03      677.5      3604.      1.000
  10.00     *   93.72      71.02      22.70      903.7      5601.      1.000
  16.00     *   10.33      17.89     -7.560      1216.      8909.      1.000
  24.00     *   3.555      2.846      .7091      1271.      9911.      1.000
 ----------------------------------------------------------------------------

 *) Starred values were included in estimation of Lambda_z.

 @) Note - the concentration at time zero (DTIME) was added for extrapolation purposes

 Dosing_time                        .0000
 Rsq                                .9671
 Rsq(adjusted)                      .9616
 Corr(x:y)                         -.9834
 Tlag                               .0000
 Tmax                              7.0000
 Cmax                            154.1144
 No._points_Lambda_z                8
 Tlast                            24.0000
 Clast                             3.5553
 AUClast                        1271.3392
 Lambda_z                           .2298
 Lambda_z_lower                    6.2500
 Lambda_z_upper                   24.0000
 t1/2_Lambda_z                     3.0165
 AUCall                         1271.3392
 AUCINF(observed)               1286.8117
 AUCINF(observed)/D                 .3574
 AUC_%Extrap(obs.)                 1.2024
 Vz(observed)/F                   12.1751
 Cl(observed)/F                    2.7976
 AUCINF(predicted)              1283.7255
 AUCINF(predicted)/D                .3566
 AUC_%Extrap(pred.)                 .9649
 Vz(predicted)/F                  12.2043
 Cl(predicted)/F                   2.8043
 AUMClast                       9911.0192
 AUMCINF(observed)             10349.6939
 AUMC_%Extrap(obs.)                4.2385
 AUMCINF(predicted)            10262.1950
 AUMC_%Extrap(pred.)               3.4220
 MRTlast                           7.7957
 MRTINF(observed)                  8.0429
 MRTINF(predicted)                 7.9941

 NORMAL ENDING

Input File: Data - [A:\DIPEDEF3.XLS]
Sex=Male
EXP=600

Start Time: 21:00:53 05-03-2014
End Time:   21:00:54 05-03-2014

          WINNONLIN NONCOMPARTMENTAL ANALYSIS PROGRAM (V01.5A)
                          Core Version 29Oct97

 Listing of input commands

TITLE 1
RTI-1117 DIPE, Isopropanol and Acetone, 600 or 3600 pm exposure to DIPE for 6 ho
MODEL 200
DATE
TIME
NVARIABLES 6
NPOINTS 100
XNUMBER 1
YNUMBER 5
DTIME 0
NCONSTANTS 1
CONSTANTS 600
METHOD 2  'Linear trapezoidal
NCATRANS
MISSING 'Missing'
NOBSERVATIONS 16
DATA 'WINNLIN.DAT'
BEGIN
                                                         Date:   05/03/2014
                                                         Time:     21:00:53
RTI-1117 DIPE, Isopropanol and Acetone, 600 or 3600 pm exposure to DIPE for 6 ho

 WINNONLIN NONCOMPARTMENTAL ANALYSIS PROGRAM

         Noncompartmental Analysis for Extravascular Administration

             Linear Trapezoidal Rule Used to Compute AUC, AUMC

  X             Y          Pred.      Res.       AUC        AUMC      WEIGHT
 ----------------------------------------------------------------------------
  .0000         .0000                            .0000      .0000
  .8333E-01     4.420                            .1842      .1535E-01
  .1667         6.568                            .6420      .7630E-01
  .2500         8.459                            1.268      .2100
  .5000         13.83                            4.055      1.339
  1.000         27.11                            14.29      9.845
  2.000         53.16                            54.42      76.56
  4.000         102.0                            209.6      591.0
  6.000     *   156.6      169.2     -12.65      468.2      1939.      1.000
  6.250     *   147.2      158.2     -11.00      506.2      2171.      1.000
  6.500     *   153.9      147.9      6.011      543.8      2411.      1.000
  7.000     *   157.8      129.3      28.49      621.8      2937.      1.000
  7.330     *   140.3      118.3      22.04      671.0      3289.      1.000
  8.000     *   128.2      98.77      29.42      760.9      3977.      1.000
  10.00     *   77.60      57.64      19.95      966.7      5779.      1.000
  16.00     *   2.376      11.46     -9.082      1207.      8221.      1.000
  24.00     *   2.829      1.329      1.500      1227.      8644.      1.000
 ----------------------------------------------------------------------------

 *) Starred values were included in estimation of Lambda_z.

 @) Note - the concentration at time zero (DTIME) was added for extrapolation purposes

 Dosing_time                        .0000
 Rsq                                .8666
 Rsq(adjusted)                      .8476
 Corr(x:y)                         -.9309
 Tlag                               .0000
 Tmax                              7.0000
 Cmax                            157.7714
 No._points_Lambda_z                9
 Tlast                            24.0000
 Clast                             2.8289
 AUClast                        1227.4261
 Lambda_z                           .2693
 Lambda_z_lower                    6.0000
 Lambda_z_upper                   24.0000
 t1/2_Lambda_z                     2.5743
 AUCall                         1227.4261
 AUCINF(observed)               1237.9324
 AUCINF(observed)/D                2.0632
 AUC_%Extrap(obs.)                  .8487
 Vz(observed)/F                    1.8001
 Cl(observed)/F                     .4847
 AUCINF(predicted)              1232.3632
 AUCINF(predicted)/D               2.0539
 AUC_%Extrap(pred.)                 .4006
 Vz(predicted)/F                   1.8082
 Cl(predicted)/F                    .4869
 AUMClast                       8644.4839
 AUMCINF(observed)              8935.6541
 AUMC_%Extrap(obs.)                3.2585
 AUMCINF(predicted)             8781.3100
 AUMC_%Extrap(pred.)               1.5582
 MRTlast                           7.0428
 MRTINF(observed)                  7.2182
 MRTINF(predicted)                 7.1256

 NORMAL ENDING

Input File: Data - [A:\DIPEDEF3.XLS]
Sex=Male
EXP=3600

Start Time: 21:00:55 05-03-2014
End Time:   21:00:56 05-03-2014

          WINNONLIN NONCOMPARTMENTAL ANALYSIS PROGRAM (V01.5A)
                          Core Version 29Oct97

 Listing of input commands

TITLE 1
RTI-1117 DIPE, Isopropanol and Acetone, 600 or 3600 pm exposure to DIPE for 6 ho
MODEL 200
DATE
TIME
NVARIABLES 6
NPOINTS 100
XNUMBER 1
YNUMBER 5
DTIME 0
NCONSTANTS 1
CONSTANTS 3600
METHOD 2  'Linear trapezoidal
NCATRANS
MISSING 'Missing'
NOBSERVATIONS 16
DATA 'WINNLIN.DAT'
BEGIN
                                                         Date:   05/03/2014
                                                         Time:     21:00:54
RTI-1117 DIPE, Isopropanol and Acetone, 600 or 3600 pm exposure to DIPE for 6 ho

 WINNONLIN NONCOMPARTMENTAL ANALYSIS PROGRAM

         Noncompartmental Analysis for Extravascular Administration

             Linear Trapezoidal Rule Used to Compute AUC, AUMC

  X             Y          Pred.      Res.       AUC        AUMC      WEIGHT
 ----------------------------------------------------------------------------
  .0000         .0000                            .0000      .0000
  .8333E-01     5.326                            .2219      .1849E-01
  .1667         7.560                            .7588      .8948E-01
  .2500         7.227                            1.375      .2173
  .5000         17.16                            4.424      1.516
  1.000         34.14                            17.25      12.20
  2.000         65.59                            67.11      94.85
  4.000         137.4                            270.1      775.5
  6.000         219.9                            627.3      2645.
  6.250         236.4                            684.4      2994.
  6.500         221.4                            741.6      3359.
  7.000         222.1                            852.5      4107.
  7.330         214.6                            924.5      4623.
  8.000     *   230.1      252.7     -22.62      1073.      5767.      1.000
  10.00     *   167.2      142.8      24.45      1471.      9279.      1.000
  16.00     *   23.55      25.74     -2.194      2043.      .1543E+05  1.000
  24.00     *   2.688      2.622      .6579E-01  2148.      .1719E+05  1.000
 ----------------------------------------------------------------------------

 *) Starred values were included in estimation of Lambda_z.

 @) Note - the concentration at time zero (DTIME) was added for extrapolation purposes

 Dosing_time                        .0000
 Rsq                                .9967
 Rsq(adjusted)                      .9950
 Corr(x:y)                         -.9983
 Tlag                               .0000
 Tmax                              6.2500
 Cmax                            236.3895
 No._points_Lambda_z                4
 Tlast                            24.0000
 Clast                             2.6883
 AUClast                        2148.0061
 Lambda_z                           .2855
 Lambda_z_lower                    8.0000
 Lambda_z_upper                   24.0000
 t1/2_Lambda_z                     2.4278
 AUCall                         2148.0061
 AUCINF(observed)               2157.4219
 AUCINF(observed)/D                 .5993
 AUC_%Extrap(obs.)                  .4364
 Vz(observed)/F                    5.8446
 Cl(observed)/F                    1.6687
 AUCINF(predicted)              2157.1915
 AUCINF(predicted)/D                .5992
 AUC_%Extrap(pred.)                 .4258
 Vz(predicted)/F                   5.8452
 Cl(predicted)/F                   1.6688
 AUMClast                      17191.2659
 AUMCINF(observed)             17450.2245
 AUMC_%Extrap(obs.)                1.4840
 AUMCINF(predicted)            17443.8867
 AUMC_%Extrap(pred.)               1.4482
 MRTlast                           8.0034
 MRTINF(observed)                  8.0885
 MRTINF(predicted)                 8.0864

 NORMAL ENDING

ISOPROPANOL

Input File: Data - [A:\DIPEDEF3.XLS]
Sex=Female
EXP=600

Start Time: 20:49:35 05-03-2014
End Time:   20:49:37 05-03-2014

          WINNONLIN NONCOMPARTMENTAL ANALYSIS PROGRAM (V01.5A)
                          Core Version 29Oct97

 Listing of input commands

TITLE 1
RTI-1117 DIPE, Isopropanol and Acetone, 600 or 3600 pm exposure to DIPE for 6 ho
MODEL 200
DATE
TIME
NVARIABLES 6
NPOINTS 100
XNUMBER 1
YNUMBER 6
DTIME 0
NCONSTANTS 1
CONSTANTS 600
METHOD 2  'Linear trapezoidal
NCATRANS
MISSING 'Missing'
NOBSERVATIONS 14
DATA 'WINNLIN.DAT'
BEGIN
                                                         Date:   05/03/2014
                                                         Time:     20:49:35
RTI-1117 DIPE, Isopropanol and Acetone, 600 or 3600 pm exposure to DIPE for 6 ho

 WINNONLIN NONCOMPARTMENTAL ANALYSIS PROGRAM

         Noncompartmental Analysis for Extravascular Administration

             Linear Trapezoidal Rule Used to Compute AUC, AUMC

  X             Y          Pred.      Res.       AUC        AUMC      WEIGHT
 ----------------------------------------------------------------------------
  .0000         .0000                            .0000      .0000
  .8333E-01     .3712                            .1547E-01  .1289E-02
  .1667         .5166                            .5246E-01  .6165E-02
  .2500         .6912                            .1028      .1695E-01
  .5000         1.020                            .3166      .1023
  1.000         1.552                            .9594      .6176
  2.000         2.758                            3.114      4.151
  4.000         5.748                            11.62      32.66
  6.000         9.560                            26.93      113.0
  6.250         9.234                            29.28      127.4
  6.500         7.252                            31.34      140.5
  7.000         4.836                            34.36      160.7
  7.330     *   3.638      3.579      .5885E-01  35.76      170.7      1.000
  8.000     *   2.216      2.264     -.4877E-01  37.72      185.6      1.000
  10.00     *   .5806      .5774      .3163E-02  40.51      209.1      1.000
 ----------------------------------------------------------------------------

 *) Starred values were included in estimation of Lambda_z.

 @) Note - the concentration at time zero (DTIME) was added for extrapolation purposes

 Dosing_time                        .0000
 Rsq                                .9996
 Rsq(adjusted)                      .9991
 Corr(x:y)                         -.9998
 Tlag                               .0000
 Tmax                              6.0000
 Cmax                              9.5595
 No._points_Lambda_z                3
 Tlast                            10.0000
 Clast                              .5806
 AUClast                          40.5142
 Lambda_z                           .6833
 Lambda_z_lower                    7.3300
 Lambda_z_upper                   10.0000
 t1/2_Lambda_z                     1.0145
 AUCall                           40.5142
 AUCINF(observed)                 41.3638
 AUCINF(observed)/D                 .0689
 AUC_%Extrap(obs.)                 2.0542
 Vz(observed)/F                   21.2299
 Cl(observed)/F                   14.5054
 AUCINF(predicted)                41.3592
 AUCINF(predicted)/D                .0689
 AUC_%Extrap(pred.)                2.0432
 Vz(predicted)/F                  21.2323
 Cl(predicted)/F                  14.5070
 AUMClast                        209.1285
 AUMCINF(observed)               218.8690
 AUMC_%Extrap(obs.)                4.4504
 AUMCINF(predicted)              218.8159
 AUMC_%Extrap(pred.)               4.4272
 MRTlast                           5.1619
 MRTINF(observed)                  5.2913
 MRTINF(predicted)                 5.2906

 NORMAL ENDING

Input File: Data - [A:\DIPEDEF3.XLS]
Sex=Female
EXP=3600

Start Time: 20:49:37 05-03-2014
End Time:   20:49:38 05-03-2014

          WINNONLIN NONCOMPARTMENTAL ANALYSIS PROGRAM (V01.5A)
                          Core Version 29Oct97

 Listing of input commands

TITLE 1
RTI-1117 DIPE, Isopropanol and Acetone, 600 or 3600 pm exposure to DIPE for 6 ho
MODEL 200
DATE
TIME
NVARIABLES 6
NPOINTS 100
XNUMBER 1
YNUMBER 6
DTIME 0
NCONSTANTS 1
CONSTANTS 3600
METHOD 2  'Linear trapezoidal
NCATRANS
MISSING 'Missing'
NOBSERVATIONS 14
DATA 'WINNLIN.DAT'
BEGIN
                                                         Date:   05/03/2014
                                                         Time:     20:49:37
RTI-1117 DIPE, Isopropanol and Acetone, 600 or 3600 pm exposure to DIPE for 6 ho

 WINNONLIN NONCOMPARTMENTAL ANALYSIS PROGRAM

         Noncompartmental Analysis for Extravascular Administration

             Linear Trapezoidal Rule Used to Compute AUC, AUMC

  X             Y          Pred.      Res.       AUC        AUMC      WEIGHT
 ----------------------------------------------------------------------------
  .0000         .0000                            .0000      .0000
  .8333E-01     .6750                            .2812E-01  .2344E-02
  .1667         .8836                            .9307E-01  .1082E-01
  .2500         2.096                            .2172      .3880E-01
  .5000         1.950                            .7230      .2262
  1.000         3.532                            2.093      1.353
  2.000         6.261                            6.990      9.380
  4.000         12.32                            25.57      71.19
  6.000         20.38                            58.28      242.8
  6.250         24.45                            63.88      277.2
  6.500         23.75                            69.91      315.6
  7.000         19.34                            80.68      388.0
  7.330     *   15.30      15.27      .3205E-01  86.39      428.8      1.000
  8.000     *   10.29      10.32     -.2883E-01  94.97      494.0      1.000
  10.00     *   3.200      3.197      .2246E-02  108.5      608.3      1.000
 ----------------------------------------------------------------------------

 *) Starred values were included in estimation of Lambda_z.

 @) Note - the concentration at time zero (DTIME) was added for extrapolation purposes

 Dosing_time                        .0000
 Rsq                               1.0000
 Rsq(adjusted)                     1.0000
 Corr(x:y)                        -1.0000
 Tlag                               .0000
 Tmax                              6.2500
 Cmax                             24.4512
 No._points_Lambda_z                3
 Tlast                            10.0000
 Clast                             3.1995
 AUClast                         108.4514
 Lambda_z                           .5857
 Lambda_z_lower                    7.3300
 Lambda_z_upper                   10.0000
 t1/2_Lambda_z                     1.1835
 AUCall                          108.4514
 AUCINF(observed)                113.9144
 AUCINF(observed)/D                 .0316
 AUC_%Extrap(obs.)                 4.7956
 Vz(observed)/F                   53.9591
 Cl(observed)/F                   31.6027
 AUCINF(predicted)               113.9105
 AUCINF(predicted)/D                .0316
 AUC_%Extrap(pred.)                4.7924
 Vz(predicted)/F                  53.9609
 Cl(predicted)/F                  31.6038
 AUMClast                        608.2650
 AUMCINF(observed)               672.2216
 AUMC_%Extrap(obs.)                9.5142
 AUMCINF(predicted)              672.1767
 AUMC_%Extrap(pred.)               9.5082
 MRTlast                           5.6086
 MRTINF(observed)                  5.9011
 MRTINF(predicted)                 5.9009

 NORMAL ENDING

Input File: Data - [A:\DIPEDEF3.XLS]
Sex=Male
EXP=600

Start Time: 20:49:38 05-03-2014
End Time:   20:49:39 05-03-2014

          WINNONLIN NONCOMPARTMENTAL ANALYSIS PROGRAM (V01.5A)
                          Core Version 29Oct97

 Listing of input commands

TITLE 1
RTI-1117 DIPE, Isopropanol and Acetone, 600 or 3600 pm exposure to DIPE for 6 ho
MODEL 200
DATE
TIME
NVARIABLES 6
NPOINTS 100
XNUMBER 1
YNUMBER 6
DTIME 0
NCONSTANTS 1
CONSTANTS 600
METHOD 2  'Linear trapezoidal
NCATRANS
MISSING 'Missing'
NOBSERVATIONS 15
DATA 'WINNLIN.DAT'
BEGIN
                                                         Date:   05/03/2014
                                                         Time:     20:49:38
RTI-1117 DIPE, Isopropanol and Acetone, 600 or 3600 pm exposure to DIPE for 6 ho

 WINNONLIN NONCOMPARTMENTAL ANALYSIS PROGRAM

         Noncompartmental Analysis for Extravascular Administration

             Linear Trapezoidal Rule Used to Compute AUC, AUMC

  X             Y          Pred.      Res.       AUC        AUMC      WEIGHT
 ----------------------------------------------------------------------------
  .0000         .0000                            .0000      .0000
  .8333E-01     .6465                            .2694E-01  .2245E-02
  .1667         .8969                            .9124E-01  .1072E-01
  .2500         1.283                            .1821      .3031E-01
  .5000         2.133                            .6090      .2037
  1.000         3.615                            2.046      1.374
  2.000         6.673                            7.190      9.854
  4.000         13.31                            27.17      76.42
  6.000         23.39                            63.86      270.0
  6.250         18.59                            69.11      302.1
  6.500         15.81                            73.41      329.4
  7.000         10.98                            80.11      374.3
  7.330         8.302                            83.29      397.0
  8.000     *   5.095      4.845      .2497      87.78      431.1      1.000
  10.00     *   1.625      1.737     -.1126      94.50      488.1      1.000
  16.00     *   .8148E-01  .8013E-01  .1354E-02  99.62      540.7      1.000
 ----------------------------------------------------------------------------

 *) Starred values were included in estimation of Lambda_z.

 @) Note - the concentration at time zero (DTIME) was added for extrapolation purposes

 Dosing_time                        .0000
 Rsq                                .9992
 Rsq(adjusted)                      .9984
 Corr(x:y)                         -.9996
 Tlag                               .0000
 Tmax                              6.0000
 Cmax                             23.3910
 No._points_Lambda_z                3
 Tlast                            16.0000
 Clast                              .0815
 AUClast                          99.6158
 Lambda_z                           .5128
 Lambda_z_lower                    8.0000
 Lambda_z_upper                   16.0000
 t1/2_Lambda_z                     1.3518
 AUCall                           99.6158
 AUCINF(observed)                 99.7747
 AUCINF(observed)/D                 .1663
 AUC_%Extrap(obs.)                  .1593
 Vz(observed)/F                   11.7278
 Cl(observed)/F                    6.0135
 AUCINF(predicted)                99.7721
 AUCINF(predicted)/D                .1663
 AUC_%Extrap(pred.)                 .1566
 Vz(predicted)/F                  11.7281
 Cl(predicted)/F                   6.0137
 AUMClast                        540.7456
 AUMCINF(observed)               543.5981
 AUMC_%Extrap(obs.)                 .5247
 AUMCINF(predicted)              543.5507
 AUMC_%Extrap(pred.)                .5161
 MRTlast                           5.4283
 MRTINF(observed)                  5.4483
 MRTINF(predicted)                 5.4479

 NORMAL ENDING

Input File: Data - [A:\DIPEDEF3.XLS]
Sex=Male
EXP=3600

Start Time: 20:49:40 05-03-2014
End Time:   20:49:41 05-03-2014

          WINNONLIN NONCOMPARTMENTAL ANALYSIS PROGRAM (V01.5A)
                          Core Version 29Oct97

 Listing of input commands

TITLE 1
RTI-1117 DIPE, Isopropanol and Acetone, 600 or 3600 pm exposure to DIPE for 6 ho
MODEL 200
DATE
TIME
NVARIABLES 6
NPOINTS 100
XNUMBER 1
YNUMBER 6
DTIME 0
NCONSTANTS 1
CONSTANTS 3600
METHOD 2  'Linear trapezoidal
NCATRANS
MISSING 'Missing'
NOBSERVATIONS 15
DATA 'WINNLIN.DAT'
BEGIN
                                                         Date:   05/03/2014
                                                         Time:     20:49:39
RTI-1117 DIPE, Isopropanol and Acetone, 600 or 3600 pm exposure to DIPE for 6 ho

 WINNONLIN NONCOMPARTMENTAL ANALYSIS PROGRAM

         Noncompartmental Analysis for Extravascular Administration

             Linear Trapezoidal Rule Used to Compute AUC, AUMC

  X             Y          Pred.      Res.       AUC        AUMC      WEIGHT
 ----------------------------------------------------------------------------
  .0000         .0000                            .0000      .0000
  .8333E-01     .9760                            .4067E-01  .3389E-02
  .1667         1.538                            .1454      .1746E-01
  .2500         1.152                            .2575      .4014E-01
  .5000         3.953                            .8957      .3232
  1.000         7.919                            3.864      2.797
  2.000         14.78                            15.21      21.54
  4.000         30.19                            60.19      171.9
  6.000         51.23                            141.6      600.0
  6.250         55.53                            155.0      681.8
  6.500     *   51.28      55.39     -4.114      168.3      766.9      1.000
  7.000     *   43.17      42.41      .7646      191.9      925.8      1.000
  7.330     *   38.68      35.55      3.130      205.4      1022.      1.000
  8.000     *   27.18      24.85      2.326      227.5      1190.      1.000
  10.00     *   7.378      8.536     -1.158      262.0      1481.      1.000
  16.00     *   .3569      .3459      .1099E-01  285.2      1720.      1.000
 ----------------------------------------------------------------------------

 *) Starred values were included in estimation of Lambda_z.

 @) Note - the concentration at time zero (DTIME) was added for extrapolation purposes

 Dosing_time                        .0000
 Rsq                                .9976
 Rsq(adjusted)                      .9970
 Corr(x:y)                         -.9988
 Tlag                               .0000
 Tmax                              6.2500
 Cmax                             55.5293
 No._points_Lambda_z                6
 Tlast                            16.0000
 Clast                              .3569
 AUClast                         285.2493
 Lambda_z                           .5343
 Lambda_z_lower                    6.5000
 Lambda_z_upper                   16.0000
 t1/2_Lambda_z                     1.2972
 AUCall                          285.2493
 AUCINF(observed)                285.9172
 AUCINF(observed)/D                 .0794
 AUC_%Extrap(obs.)                  .2336
 Vz(observed)/F                   23.5640
 Cl(observed)/F                   12.5911
 AUCINF(predicted)               285.8966
 AUCINF(predicted)/D                .0794
 AUC_%Extrap(pred.)                 .2264
 Vz(predicted)/F                  23.5657
 Cl(predicted)/F                  12.5920
 AUMClast                       1719.8935
 AUMCINF(observed)              1731.8289
 AUMC_%Extrap(obs.)                 .6892
 AUMCINF(predicted)             1731.4612
 AUMC_%Extrap(pred.)                .6681
 MRTlast                           6.0294
 MRTINF(observed)                  6.0571
 MRTINF(predicted)                 6.0562

 NORMAL ENDING

Appendix G
Example CalculationsFormulae for Calculations
Formulae used in the Debra system for calculations are shown below:
Aliquot dpm/g is calculated by:
dpm/g = aliquot corrected count (dpm) / aliquot weight (g)
The mean of these aliquot figures for the sample is calculated by:
Mean dpm/g = Sum of all aliquot dpm/g / number of aliquots
The weight of the sample used for calculations is calculated from the pot weight (before sample collection) and sample weight (weight of pot + sample):
Weight of the sample = sample weight  -  pot weight
Depending on the nature of the sample processing, Effective weight may be one of a number of values:
If processing type does not use homogenate (e.g. for urine, exhaled VOC trap, CO2 trap, Cage Wash) then:
Effective weight = weight of the sample
If processing type uses homogenate (e.g. for feces and carcass) then:
Effective weight = Homogenate weight
To calculate the total dpm in the sample, Debra uses the previously calculated figures;
Total Dpm = Mean dpm/g * Effective weight
For inhalation exposure, where the dpm administered is not precisely known, the Dose Dpm is calculated as the sum of all dpm recovered for each animal.
Recovery is calculated by:
Recovery = 100* (Total Dpm/ Dose Dpm)
Concentration is calculated by:
Concentration = (Total dpm/ effective weight) / (Specific activity)
Results are expressed in terms of the arithmetic mean  standard deviation. Mean values were calculated using:

Standard deviation was calculated using:
Example Calculations
Examples of the calculations for urine, feces, exhaled VOC trap, CO2 trap, and cage rinse made in the Debra(TM) system are shown below:
Subject		= 1-01
Sample		= Urine
Time point	= 24 h
Aliquot 1 dpm/g	= 3890.6675/0.0603
		= 64521.849088 dpm/g
Aliquot 2 dpm/g	= 3263.1575/0.0508
		= 64235.383858 dpm/g
Sum of dpm/g	=<PHONE_NUMBER> dpm/g
Number of aliquots	= 2

Mean dpm/g	= Sum of dpm/g / Number of aliquots
		=<PHONE_NUMBER> / 2
		= dpm/g

Recovery Effective Wt
		= Sample weight
		= 8.5440g

Concentration Effective Weight
		= Sample weight
		= 8.5440g

Total dpm		= Dpm/g x Recovery effective weight
		= 64378.61647 x 8.5440
		=<PHONE_NUMBER> dpm

Dose dpm (using Exposure Dose)
		= sum of all dpm recovered
		= 11918767.56 dpm

Recovery		= 100 x (Total dpm / Dose dpm)
		= 100 x<PHONE_NUMBER> / 11918767.56)
		= 100 x (0.046149981)
		= 4.614998%

Concentration	= (Total dpm/Concentration effective weight) / (Specific activity)
		=<PHONE_NUMBER> / 8.5440) / (0.3756 uCi/mg * 2.22E6 DPM/uCi)
		=<PHONE_NUMBER> dpm/g) / (833832 dpm/mg)
		= 0.077208138 mg/g

Subject		= 1-01
Sample		= Feces
Time point	= 24 h
Aliquot 1 dpm/g	= 339.405/0.0734
		= 4624.046322 dpm/g
Aliquot 2 dpm/g	= 406.235/0.0873
		= 4653.321879 dpm/g
Sum of dpm/g	= 9277.368201 dpm/g
Number of aliquots	= 2

Mean dpm/g	= Sum of dpm/g / Number of aliquots
		= 9277.368201 / 2
		= 4638.6841 dpm/g

Recovery Effective Weight
		= Homogenate weight
		= 18.8659g

Concentration Effective Weight
		= Sample weight
		= 8.0941g

Total dpm		= Dpm/g x Recovery effective weight
		= 4638.684100 x 18.8659
		= 87512.9504 dpm

Dose dpm (using Exposure Dose)
		= sum of all dpm recovered
		= 11918767.56 dpm

Recovery		= 100 x (Total dpm / Dose dpm)
		= 100 x (87512.9504/ 11918767.56)
		= 100 x (0.00734245)
		= 0.734245 %

Concentration	= (Total dpm/Concentration effective weight) / (Specific activity)
		= (87512.9504/ 8.0941) / (0.3756 uCi/mg)
		= (10811.94332 dpm/g) / (833832 dpm/mg)
		= 0.012966573 mg/g

Subject		= 1-01
Sample		= Carcass Digest
Time point	= 24 h
Aliquot 1 dpm/g	= 1501.160 / 0.9480
		= 1583.50211 dpm/g
Aliquot 2 dpm/g	= 1401.790 / 0.8920
		= 1569.929443 dpm/g
Sum of dpm/g	= 3153.431553 dpm/g
Number of aliquots	= 2

Mean dpm/g	= Sum of dpm/g / Number of aliquots
		= 3153.431553 / 2
		= 1576.715777 dpm/g

Recovery Effective Weight
		= Homogenate weight
		= 553.80 g

Concentration Effective Weight
		= Sample weight
		= 130.32 g

Total dpm		= Dpm/g x Recovery effective weight
		= 1576.715777 x 553.80
		= 873185.197 dpm

Dose dpm (using Exposure Dose)
		= sum of all dpm recovered
		= 11918767.56 dpm

Recovery		= 100 x (Total dpm / Dose dpm)
		= 100 x (873185.197 / 11918767.56)
		= 100 x (0.073261366)
		= 7.326137 %

Concentration	= (Total dpm/Concentration effective weight) / (Specific activity)
		= (873185.197 / 130.32) / (0.3756 uCi/mg)
		= (6700.316122 dpm/g) / (833832 dpm/mg)
		= 0.008035571 mg/g

Subject		= 1-01
Sample		= CO2 Trap 1
Time point	= 24 h
Aliquot 1 dpm/g	= 2462.926/1.0409
		= 2366.15045 dpm/g
Aliquot 2 dpm/g	= 2462.026/1.0411
		= 2364.83143dpm/g
Sum of dpm/g	= 4730.98188 dpm/g
Number of aliquots	= 2

Mean dpm/g	= Sum of dpm/g / Number of aliquots
		= 4730.98188 / 2
		= 2365.490938 dpm/g

Recovery Effective Wt
		= Sample weight
		= 523.60 g

Concentration Effective Weight
		= Sample weight
		= 523.60 g

Total dpm		= Dpm/g x Recovery effective weight
		= 2365.490938 x 523.60
		= 1238571.0549 dpm

Dose dpm (using Exposure Dose)
		= sum of all dpm recovered
		= 11918767.56 dpm

Recovery		= 100 x (Total dpm / Dose dpm)
		= 100 x (1238571.0549 / 11918767.56)
		= 100 x (0.103917712)
		= 10.39177%

Concentration	= (Total dpm/Concentration effective weight) / (Specific activity)
		= (1238571.0549 / 523.6) / (0.3756 uCi/mg)
		= (2365.490938 dpm/g) / (833832 dpm/mg)
		= 0.002836892 mg/g

Subject		= 1-01
Sample		= Exhaled VOC Trap 1
Time point	= 24 h
Aliquot 1 dpm/g	= 396.568 / 0.0490
		= 8093.22449 dpm/g
Aliquot 2 dpm/g	= 391.698 / 0.0494
		= 7929.10931 dpm/g
Sum of dpm/g	= 16022.3338 dpm/g
Number of aliquots	= 2

Mean dpm/g	= Sum of dpm/g / Number of aliquots
		= 16022.3338 / 2
		= 8011.166901 dpm/g

Recovery Effective Wt
		= Sample weight
		= 7.4559 g

Concentration Effective Weight
		= Sample weight
		= 7.4559 g

Total dpm		= Dpm/g x Recovery effective weight
		= 8011.166901 x 7.4559
		= 59730.45929 dpm

Dose dpm (using Exposure Dose)
		= sum of all dpm recovered
		= 11918767.56 dpm

Recovery		= 100 x (Total dpm / Dose dpm)
		= 100 x (59730.45929 / 11918767.56)
		= 100 x (0.005011463)
		= 0.5011463 %

Concentration	= (Total dpm/Concentration effective weight) / (Specific activity)
		= (59730.45929 / 7.4559) / (0.3756 uCi/mg)
		= (8011.1669 dpm/g) / (833832 dpm/mg)
		= 0.009607651 mg/g

Subject		= 1-01
Sample		= Cage Rinse
Time point	= 24 h
Aliquot 1 dpm/g	= 127.7175/0.6374
		= 200.372607dpm/g
Aliquot 2 dpm/g	= 116.2475 / 0.5603
		= 207.473675 dpm/g
Sum of dpm/g	= 407.846282 dpm/g
Number of aliquots	= 2

Mean dpm/g	= Sum of dpm/g / Number of aliquots
		= 407.846282 / 2
		= 203.923141 dpm/g

Recovery Effective Wt
		= Sample weight
		= 264.98 g

Concentration Effective Weight
		= Sample weight
		= 264.98 g

Total dpm		= Dpm/g x Recovery effective weight
		= 203.923141 x 264.98
		= 54035.5539 dpm

Dose dpm (using Exposure Dose)
		= sum of all dpm recovered
		= 11918767.56 dpm

Recovery		= 100 x (Total dpm / Dose dpm)
		= 100 x (54035.5539 / 11918767.56)
		= 100 x (0.004533653)
		= 0. 4533653 %

Concentration	= (Total dpm/Concentration effective weight) / (Specific activity)
		= (54035.5539 / 264.98) / (0.3756 uCi/mg)
		= (203.923141 dpm/g) / (833832 dpm/mg)
		= 0.000244561 mg/g

Appendix H
Raw Data Tables

Sample Naming and Abbreviations
In the tables of raw data values in this appendix, the table headings are derived from the conventions of sample naming used in the Debra system.  These are explained below.  Example calculations and formulae are provided in Appendix G.

                                Column Heading
                                    Source
                                  Explanation
Subject

Animal number
Sample

The type of sample, e.g. urine, feces
Time

The time of sample collection
Pot wt.
Balance
The weight of the empty sample container
Samp wt.
Balance
Sample weight,  the weight of sample + empty sample container
Corr Samp
Calculated
The corrected sample weight, calculated from Samp wt.  -  Pot wt.
Homog wt.
Balance
For samples requiring homogenization, the weight of pot + sample + medium for homogenization.
Corr Homog
Calculated
Corrected Homogenate Weight,
calculated from Homog Wt  -  Samp Wt.
Alq wt.
Balance
Aliquot weight, weight of aliquot removed for scintillation counting
Orig DPM
Scintillation Counter
Original DPM, the DPM measured in each aliquot.
Bkg DPM
Scintillation Counter
The background DPM determined for the batch of samples
Corr DPM
Calculated
The calculated DPM for the aliquot, = Orig DPM  -  Calc DPM
LOD
Calculated
Limit of Detection.  If Orig DPM value is less than Bkg DPM then the sample is flagged with an **
LOQ
Calculated
Limit of Quantitation.  If Orig DPM value is less than 3 x Bkg DPM, then the sample is flagged with an *
DPM/g
Calculated
Calculated value of DPM/g sample.
Sample DPM
Calculated
Total DPM in the sample.
Reco (%)
Calculated