This file provides substance-specific information relevant to the UDP
and ATC method test simulations for two of the regressions evaluated in
the BRD:

-   RC Millimole Regression (3T3 NRU used 46 substances; NHK NRU used 47
    substances)

-   RC Rat-Only Weight Regression Excluding Chemicals with Specific
    Mechanisms of Action for (3T3 NRU used 46 substances; NHK NRU used
    47 substances)

Data for dose-mortality response slope = 2 is shown.

**Table 1 Animal Use/Deaths for the UDP^1^ by Substance Using Starting
Doses Based on the 3T3 NRU Test Method with the RC Millimole
Regression^2^**, Dose-Response Slope = 2

  ------------------------------------------------------------------------------------------------------------------------------------------------------------
  **Substance**           **Reference   **IC~50~     **NRU         **NRU          **Predicted    **#Animals   **#Animals              **#Animals   **\#
                          LD~50~        (mM)**       Predicted     Predicted      Starting Dose  Used for     Used for                Dead for     Animals
                          (mg/kg)**                  LD~50~        Starting Dose  -- Default     Predicted    Default                 Predicted    Dead for
                                                     (mg/kg)**     (mg/kg)^3^**   Starting Dose  Starting     Starting                Starting     Default
                                                                                  (mg/kg)^4^**   Dose^5^**    Dose^5^**               Dose^5^**    Starting
                                                                                                                                                   Dose^5^**
  ----------------------- ------------- ------------ ------------- -------------- -------------- ------------ ------------ ---------- ------------ -----------
  ***LD~50~ ≤ 5 mg/kg***                                                                                                                           

  Mercury II chloride     1             0.02         186.37        175            0              11.99        12\. 14                 8.86         9.13

  Triethylene-melamine    1             0.0033       57.62         55             -120           11.04        12.28                   7.78         9.17

  Sodium selenate         2             0.19         362.29        175            0              11.81        11.82                   8.2          8.19

  Cycloheximide           2             0.001        53.2          17.5           -157.5         9.59         11.81                   6.01         7.9

  Busulfan                2             0.54         696.28        550            375            12.2         11.5                    8.44         7.79

  Aminopterin             3             0.000016     14.72         5.5            -169.5         7.52         11.73        4.11                    7.51

  Phenylthiourea          3             0.94         535.95        175            0              11.47        11.01                   7.59         1.17

  **Category Mean**       **1.94**      **0.24**     **272.35**    **164.71**     **-10.29**     **10.80**    **11.69**               **7.28**     **7.27**

  ***5 \< LD~50~ ≤ 50                                                                                                                              
  mg/kg***                                                                                                                                         

  Digoxin                 18            0.71         2713.65       1750           1575           11.91        8.74                    7.77         5.24

  Arsenic III trioxide    20            0.01         116.7         55             -120           8.07         9.76                    4.36         5.63

  Thallium I sulfate      29            0.02         325.22        175            0              9.01         9.08                    5.1          5.14

  Sodium arsenite         41            0.01         59.87         55             -120           7.9          8.91                    3.95         4.86

  Triphenyltin hydroxide  44            0.000068     21.64         17.5           -157.5         8.88         8.84                    4.07         4.78

  Sodium dichromate       50            0.002        84.05         55             -120           7.66         8.5          3.89                    4.56
  dihydrate                                                                                                                                        

  **Category Mean**       **33.63**     **0.13**     **553.52**    **351.25**     **176.25**     **8.91**     **8.97**                **4.86**     **5.04**

  ***50 \< LD~50~ ≤ 300                                                                                                                            
  mg/kg***                                                                                                                                         

  Hexachlorophene         61            0.01         237.67        175            0              8.12         8.17                    4.36         4.38

  Cadmium II chloride     88            0.0031       61.11         55             -120           8.13         7.83                    3.89         4.03

  Sodium oxalate          155           0.32         331.01        175            0              7.12         7.19                    3.6          3.62

  Sodium fluoride         180           1.9          232.55        175            0              7.15         7.1                     3.57         3.54

  Diquat dibromide        243           0.04         320.72        175            0              7.45         7.39                    3.63         3.63

  Cupric sulfate \* 5 H2O 300           0.45         575.49        550            375            7.67         7.62                    3.77         3.7

  **Category Mean**       **171.21**    **0.45**     **293.09**    **217.50**     **42.50**      **7.61**     **7.55**                **3.80**     **3.82**

  ***300 \< LD~50~ ≤ 2000                                                                                                                          
  mg/kg***                                                                                                                                         

  Phenol                  414           0.75         344.55        175            0              7.99         7.94                    3.76         3.73

  Propranolol HCl         470           0.05         334.45        175            0              8.03         8.11                    3.72         3.78

  Meprobamate             794           2.66         1372.57       550            375            7.79         8.89                    3.8          4.01

  Acetylsalicylic acid    1000          4.27         1387.32       550            375            7.81         9.19                    3.75         4.03

  Lithium carbonate       1187          7.68         755.11        550            375            7.95         9.55                    3.73         4.11

  Valproic acid           1471          7.95         1426.22       550            375            8.14         9.99                    3.72         4.08

  **Category Mean**       **889.31**    **3.89**     **936.70**    **425.00**     **250.00**     **7.95**     **8.95**     **3.75**                **3.96**

  ***2000 \< LD~50~ ≤                                                                                                                              
  5000 mg/kg***                                                                                                                                    

  Acetaminophen           2404          0.33         389.83        175            0              10.06        10.14                   3.81         3.83

  Potassium I chloride    2602          49.34        1700.88       550            375            8.48         10.57                   3.58         3.95

  Boric aid               2660          36.96        1188.15       550            375            9.09         10.43                   3.71         3.86

  Dimethylform-amide      2800          71.64        1974.68       1750           1575           7.84         10.81                   3.45         3.93

  Sodium chloride         2998          81.21        166.93        55             -120           9.21         10.77                   3.62         3.84

  Citric Acid             3000          4.54         1526.62       550            375            9.04         10.7                    3.6          3.83

  Chloramphenicol         3393          0.51         951.97        550            375            9.63         10.81                   3.56         3.67

  Lactic acid             3730          34.1         1758.84       1750           1575           9.07         11.02                   3.43         3.63

  Acetonitrile            3798          209.25       1735.66       550            375            9.22         11.01                   3.46         3.63

  Xylene                  4300          6.83         1030.68       550            375            9.94         10.95        3.63                    3.34

  Trichloroacetic acid    4999          5.79         1467.83       550            375            9.94         11.03                   3.08         3.11

  **Category Mean**       **3334.91**   **43.50**    **1411.93**   **750.00**     **575.00**     **9.47**     **10.92**               **3.46**     **3.54**

                                                                                                                                                   

  ***LD~50~ \> 5000                                                                                                                                
  mg/kg***                                                                                                                                         

  2-Propanol              5843          61.67        1514.63       550            375            9.96         10.86                   2.82         2.77

  Gibberellic acid        6305          22.76        5680.82       5000           4825           7.85         10.66                   2.56         2.6

  5-Aminosalicylic acid   7749          11.13        1832.59       1750           1575           8.68         10.12                   2.11         2.03

  Ethylene glycol         8567          405.23       3531.52       1750           1575           8.01         9.9                     1.88         1.82

  Diethylphthalate        8602          0.51         690.8         550            375            9.23         9.71                    1.91         1.76

  Sodium hypochlorite     8910          17.67        1048.24       550            375            9.02         9.77                    1.82         1.75

  1,1,1-Trichloroethane   10298         150.56       4812.26       1750           1575           6.66         9.17                    1.49         1.38

  Dibutylphthalate        11998         0.33         620.23        550            375            8.22         8.81                    1.11         1.16

  Glycerol                12691         331.64       4583.36       1750           1575           5.98         8.63                    1.04         1.06

  Ethanol                 14008         145.42       1680.12       550            375            6.89         8.27                    0.87         0.9

  **Category Mean**       **9497.17**   **114.69**   **2599.46**   **1475.00**    **1300.00**    **8.05**     **9.59**                **1.76**     **1.72**
  ------------------------------------------------------------------------------------------------------------------------------------------------------------

^1^OECD (2001a); EPA (2002a).

^2^RC millimole regression is log LD~50~ (mmol/kg) = 0.435 log IC~50~
(mM) + 0.625.

^3^Starting dose was one default dose lower than the predicted LD~50~
calculated using the geometric mean of the laboratory geometric mean 3T3
NRU IC~50~ values in the RC millimole regression.

^4^Default starting dose = 175 mg/kg.

^5^Numbers are mean numbers of animals for 2000 simulations for each
substance with a limit dose of 5000 mg/kg. Although the simulations used
whole animals, averaging the results produced fractional numbers of
animals. Results are provided for 46 substances in the 3T3 NRU test
method categorized using the initial LD~50~ values from **Table 3-2**.

**Table 2 Animal Use/Deaths for the UDP^1^ by Substance Using Starting
Doses Based on the NHK NRU Test Method with the RC Millimole
Regression^2^**, Dose-Response Slope = 2

  ---------------------------------------------------------------------------------------------------------------------------------------------------------
  **Substance**           **Reference    **IC~50~     **NRU         **NRU          **Predicted    **#Animals   **#Animals          **#Animals   **\#
                          LD~50~         (mM)**       Predicted     Predicted      Starting Dose  Used for     Used for            Dead for     Animals
                          (mg/kg)**                   LD~50~        Starting Dose  -- Default     Predicted    Default             Predicted    Dead for
                                                      (mg/kg)**     (mg/kg)^3^**   Starting Dose  Starting     Starting            Starting     Default
                                                                                   (mg/kg)^4^**   Dose^5^**    Dose^5^**           Dose^5^**    Starting
                                                                                                                                                Dose^5^**
  ----------------------- -------------- ------------ ------------- -------------- -------------- ------------ ------------ ------ ------------ -----------
  ***LD~50~ ≤ 5 mg/kg***                                                                                                                        

  Mercury II chloride     1              0.02         186.37        175            0              11.99        12\. 14             8.86         9.13

  Triethylene-melamine    1              0.0033       57.62         55             -120           11.04        12.28               7.78         9.17

  Sodium selenate         2              0.19         362.29        175            0              11.81        11.82               8.2          8.19

  Cycloheximide           2              0.001        53.2          17.5           -157.5         9.59         11.81               6.01         7.9

  Busulfan                2              0.54         696.28        550            375            12.2         11.5                8.44         7.79

  Aminopterin             3              0.000016     14.72         5.5            -169.5         7.52         11.73        4.11                7.51

  Phenylthiourea          3              0.94         535.95        175            0              11.47        11.01               7.59         1.17

  **Category Mean**       **1.94**       **0.24**     **272.35**    **164.71**     **-10.29**     **10.80**    **11.69**           **7.28**     **7.27**

  ***5 \< LD~50~ ≤ 50                                                                                                                           
  mg/kg***                                                                                                                                      

  Digoxin                 18             0.71         2713.65       1750           1575           11.91        8.74                7.77         5.24

  Arsenic III trioxide    20             0.01         116.7         55             -120           8.07         9.76                4.36         5.63

  Thallium I sulfate      29             0.02         325.22        175            0              9.01         9.08                5.1          5.14

  Sodium arsenite         41             0.01         59.87         55             -120           7.9          8.91                3.95         4.86

  Triphenyltin hydroxide  44             0.000068     21.64         17.5           -157.5         8.88         8.84                4.07         4.78

  Sodium dichromate       50             0.002        84.05         55             -120           7.66         8.5          3.89                4.56
  dihydrate                                                                                                                                     

  **Category Mean**       **33.63**      **0.13**     **553.52**    **351.25**     **176.25**     **8.91**     **8.97**            **4.86**     **5.04**

  ***50 \< LD~50~ ≤ 300                                                                                                                         
  mg/kg***                                                                                                                                      

  Hexachlorophene         61             0.01         237.67        175            0              8.12         8.17                4.36         4.38

  Cadmium II chloride     88             0.0031       61.11         55             -120           8.13         7.83                3.89         4.03

  Sodium oxalate          155            0.32         331.01        175            0              7.12         7.19                3.6          3.62

  Sodium fluoride         180            1.9          232.55        175            0              7.15         7.1                 3.57         3.54

  Diquat dibromide        243            0.04         320.72        175            0              7.45         7.39         3.63                3.63

  Cupric sulfate \* 5 H2O 300            0.45         575.49        550            375            7.67         7.62                3.77         3.7

  **Category Mean**       **171.21**     **0.45**     **293.09**    **217.50**     **42.50**      **7.61**     **7.55**            **3.80**     **3.82**

  ***300 \< LD~50~ ≤ 2000                                                                                                                       
  mg/kg***                                                                                                                                      

  Phenol                  414            0.75         344.55        175            0              7.99         7.94                3.76         3.73

  Propranolol HCl         470            0.05         334.45        175            0              8.03         8.11                3.72         3.78

  Meprobamate             794            2.66         1372.57       550            375            7.79         8.89                3.8          4.01

  Acetylsalicylic acid    1000           4.27         1387.32       550            375            7.81         9.19                3.75         4.03

  Lithium carbonate       1187           7.68         755.11        550            375            7.95         9.55                3.73         4.11

  Valproic acid           1471           7.95         1426.22       550            375            8.14         9.99                3.72         4.08

  **Category Mean**       **889.31**     **3.89**     **936.70**    **425.00**     **250.00**     **7.95**     **8.95**            **3.75**     **3.96**

  ***2000 \< LD~50~ ≤                                                                                                                           
  5000 mg/kg***                                                                                                                                 

  Acetaminophen           2404           0.33         389.83        175            0              10.06        10.14               3.81         3.83

  Potassium I chloride    2602           49.34        1700.88       550            375            8.48         10.57               3.58         3.95

  Boric aid               2660           36.96        1188.15       550            375            9.09         10.43               3.71         3.86

  Dimethylform-amide      2800           71.64        1974.68       1750           1575           7.84         10.81               3.45         3.93

  Sodium chloride         2998           81.21        166.93        55             -120           9.21         10.77               3.62         3.84

  Citric Acid             3000           4.54         1526.62       550            375            9.04         10.7                3.6          3.83

  Chloramphenicol         3393           0.51         951.97        550            375            9.63         10.81               3.56         3.67

  Lactic acid             3730           34.1         1758.84       1750           1575           9.07         11.02               3.43         3.63

  Acetonitrile            3798           209.25       1735.66       550            375            9.22         11.01               3.46         3.63

  Xylene                  4300           6.83         1030.68       550            375            9.94         10.95               3.63         3.34

  Trichloroacetic acid    4999           5.79         1467.83       550            375            9.94         11.03        3.08                3.11

  **Category Mean**       **3334.91**    **43.50**    **1411.93**   **750.00**     **575.00**     **9.47**     **10.92**           **3.46**     **3.54**

  **LD~50~ \> 5000                                                                                                                              
  mg/kg**                                                                                                                                       

  2-Propanol              5843           61.67        1514.63       550            375            9.96         10.86               2.82         2.77

  Gibberellic acid        6305           22.76        5680.82       5000           4825           7.85         10.66               2.56         2.6

  5-Aminosalicylic acid   7749           11.13        1832.59       1750           1575           8.68         10.12               2.11         2.03

  Ethylene glycol         8567           405.23       3531.52       1750           1575           8.01         9.9                 1.88         1.82

  Diethylphthalate        8602           0.51         690.8         550            375            9.23         9.71                1.91         1.76

  Sodium hypochlorite     8910           17.67        1048.24       550            375            9.02         9.77                1.82         1.75

  1,1,1-Trichloroethane   10298          150.56       4812.26       1750           1575           6.66         9.17                1.49         1.38

  Dibutylphthalate        11998          0.33         620.23        550            375            8.22         8.81                1.11         1.16

  Glycerol                12691          331.64       4583.36       1750           1575           5.98         8.63                1.04         1.06

  Methanol                13012          51.02        735.52        550            175            7.58         8.44                1            0.98

  Ethanol                 14008          145.42       1680.12       550            375            6.89         8.27                0.87         0.9

  **Category Mean**       **10214.07**   **113.63**   **2521.55**   **1475.00**    **1280.00**    **7.81**     **9.35**            **1.58**     **1.54**
  ---------------------------------------------------------------------------------------------------------------------------------------------------------

^1^OECD (2001a); EPA (2002a).

^2^RC millimole regression is log LD~50~ (mmol/kg) = 0.435 log IC~50~
(mM) + 0.625.

^3^Starting dose was one default dose lower than the predicted LD~50~
calculated using the geometric mean of the laboratory geometric mean NHK
NRU IC~50~ values in the RC millimole regression.

^4^Default starting dose = 175 mg/kg.

^5^Numbers are mean numbers of animals for 2000 simulations for each
substance with a limit dose of 5000 mg/kg. Although the simulations used
whole animals, averaging the results produced fractional numbers of
animals. Results are provided for 47 substances in the NHK NRU test
method categorized using the initial LD~50~ values from **Table 3-2**.

**Table 3 Animal Use/Deaths for the UDP^1^ by Substance Using Starting
Doses Based on the 3T3 NRU Test Method for the RC Rat-Only Weight
Regression Excluding Substances with Specific Mechanisms of
Toxicity^2^**, Dose-Response Slope = 2

  -----------------------------------------------------------------------------------------------------------------------------------------------------
  **Substance**           **Reference   **IC~50~      **NRU         **NRU          **Predicted    **#Animals   **#Animals      **#Animals   **\#
                          LD~50~        (g/mL)**      Predicted     Predicted      Starting Dose  Used for     Used for        Dead for     Animals
                          (mg/kg)**                   LD~50~        Starting Dose  -- Default     Predicted    Default         Predicted    Dead for
                                                      (mg/kg)**     (mg/kg)^3^**   Starting Dose  Starting     Starting        Starting     Default
                                                                                   (mg/kg)^4^**   Dose^5^**    Dose^5^**       Dose^5^**    Starting
                                                                                                                                            Dose^5^**
  ----------------------- ------------- ------------- ------------- -------------- -------------- ------------ ------------ -- ------------ -----------
  ***LD~50~ ≤ 5 mg/kg***                                                                                                                    

  Cycloheximide           2             0.28          90.67         55             -120           10.24        11.72           6.59         7.85

  Phenylthiourea          3             142.70        796.72        550            375            11.97        10.89           8.05         7.11

  Sodium selenate         3             35.05         528.45        175            0              12.22        11.71           8.58         8.13

  Triethylene-melamine    4             0.66          110.88        55             -120           11.49        12.24           8.34         9.15

  **Category Mean**       **3.00**      **44.67**     **381.68**    **208.75**     **33.75**      **11.48**    **11.64**       **7.89**     **8.06**

  ***5 \< LD~50~ ≤ 50                                                                                                                       
  mg/kg***                                                                                                                                  

  Aminopterin             7             0.01          25.9          17.5           -157.5         8.37         11.57           4.88         7.43

  Busulfan                12            131.99        791.64        550            375            12.34        11.48           8.61         7.78

  Thallium I sulfate      25            8.15          305.77        175            0              8.97         9.08            5.07         5.14

  Arsenic III trioxide    25            2.40          204.51        175            0              9.09         9.54            5.19         5.54

  Digoxin                 28            552.08        1429.42       550            375            11.02        8.99            6.86         5.34

  Mercury II chloride     40            4.29          260.35        175            0              12.19        12.17           9.10         9.15

  Sodium arsenite         44            0.86          1440.2        550            375            7.86         8.78            4.07         4.80

  **Category Mean**       **25.86**     **99.97**     **636.83**    **313.21**     **138.21**     **9.98**     **10.23**       **6.25**     **6.45**

  ***50 \< LD~50~ ≤ 300                                                                                                                     
  mg/kg***                                                                                                                                  

  Sodium dichromate       51            0.60          129.85        55             -120           7.66         8.50            3.89         4.56
  dihydrate                                                                                                                                 

  Hexachlorophene         82            4.49          263.31        175            0              8.12         8.18            4.37         4.39

  Sodium I fluoride       127           4746.03       3200.90       1750           1575           7.85         11.03           3.40         3.96

  Cadmium II chloride     135           0.56          125.02        55             -120           7.65         7.84            3.77         4.03

  Diquat dibromide        160           13.63         350.71        175            0              7.31         7.37            3.59         3.62

  **Category Mean**       **111.00**    **953.06**    **813.96**    **442**        **267**        **7.72**     **8.58**        **3.8**      **4.11**

                                                                                                                                            

                                                                                                                                            

  ***300 \< LD~50~ ≤ 2000                                                                                                                   
  mg/kg***                                                                                                                                  

  Triphenyltin hydroxide  329           0.02          38.37         17.5           -157.5         8.21         8.90            3.93         4.80

  Propranolol HCl         466           14.88         403.88        175            0              8.03         8.12            3.72         3.78

  Cupric sulfate \* 5 H2O 474           111.21        664.10        550            375            7.64         7.64            3.81         3.72

  Phenol                  548           70.61         703.52        550            375            7.62         8.01            3.81         3.84

  Lithium carbonate       590           567.71        1499.89       550            375            7.95         9.55            3.73         4.11

  Sodium oxalate          633           42.41         580.07        550            375            7.94         7.44            4.17         3.77

  Valproic acid           995           1146.26       1843.36       1750           1575           7.82         10.20           3.66         4.19

  Meprobamate             1387          581.19        1478.07       550            375            7.82         8.90            3.82         4.01

  Acetylsalicylic acid    1506          768.77        1629.08       550            375            7.80         9.27            3.79         4.08

  **Category Mean**       **769.78**    **367.01**    **982.26**    **582.5**      **407.5**      **7.87**     **8.67**        **3.83**     **4.03**

  ***2000 \< LD~50~ ≤                                                                                                                       
  5000 mg/kg***                                                                                                                             

  Acetaminophen           2163          50.30         625.18        550            375            9.10         10.30           3.75         3.90

  Potassium I chloride    2799          3677.93       2905.00       1750           1575           7.64         10.79           3.44         4.06

  Boric aid               3426          2285.43       2348.46       1750           1575           8.04         10.66           3.56         3.96

  5-Aminosalicylic acid   3429          1704.52       2213.35       1750           1575           8.43         10.11           2.13         2.03

  Chloramphenicol         3491          165.65        908.65        550            375            9.61         10.80           3.55         3.67

  Acetonitrile            3598          8589.69       3888.93       1750           1575           8.28         11.11           3.40         3.68

  Lactic acid             3639          3071.29       2736.86       1750           1575           8.48         11.06           3.36         3.64

  Sodium chloride         4046          4746.03       3200.90       1750           1575           7.85         11.03           3.40         3.96

  Xylene                  4667          724.77        1636.53       550            375            9.87         10.94           3.35         3.57

  **Category Mean**       **3473.11**   **2779.51**   **2273.76**   **1350**       **1175**       **8.59**     **10.76**       **3.33**     **3.61**

  ***LD~50~ \> 5000                                                                                                                         
  mg/kg***                                                                                                                                  

  2-Propanol              5105          3707.11       2919.27       1750           1575           8.93         10.89           3.27         2.78

  Trichloroacetic acid    5229          946.08        1789.72       1750           1575           9.38         11.04           3.08         3.11

  Dimethylform-amide      5309          5236.65       3315.71       1750           1575           7.84         10.81           3.45         3.93

  Citric Acid             5929          872.08        1711.56       550            375            8.73         10.72           3.55         3.85

  Gibberellic acid        6040          7883.7        3835.72       1750           1575           8.76         10.67           2.62         2.60

  Ethylene glycol         7161          25152.44      5754.18       5000           4825           7.08         9.90            1.83         1.82

  Dibutylphthalate        8892          93.03         678.46        550            375            8.11         8.81            1.12         1.16

  Diethylphthalate        9311          113.88        836.07        550            375            9.16         9.71            1.91         1.76

  Sodium hypochlorite     10328         1315.42       1946.61       1750           1575           8.35         9.77            1.80         1.75

  Ethanol                 11324         6699.71       3593.75       1750           1575           6.12         8.26            0.87         0.90

  1,1,1-Trichloroethane   12078         20086.61      5188.88       5000           4825           6.54         9.18            1.49         1.38

  Glycerol                19770         30540.55      5904.77       5000           4825           5.62         8.63            1.01         1.06

  **Category Mean**       **8873.00**   **8553.94**   **3122.89**   **2262.5**     **2087.5**     **7.89**     **9.87**        **2.17**     **2.18**
  -----------------------------------------------------------------------------------------------------------------------------------------------------

^1^OECD (2001a); EPA (2002a).

^2^RC Rat-only weight regression excluding substances with specific
mechanisms of toxicity is log LD~50~ (mg/kg) = 0.357 log IC~50~ (g/mL) +
2.194

^3^Starting dose was one default dose lower than the predicted LD~50~
calculated using the geometric mean of the laboratory geometric mean 3T3
NRU IC~50~ values in the RC Rat-only weight regression excluding
substances with specific mechanisms of toxicity.

^4^Default starting dose = 175 mg/kg.

^5^Numbers are mean numbers of animals for 2000 simulations for each
substance with a limit dose of 5000 mg/kg. Although the simulations used
whole animals, averaging the results produced fractional numbers of
animals. Results are provided for 46 substances in the 3T3 NRU test
method categorized using the reference LD~50~ values from **Table 4-2**.

**Table 4 Animal Use/Deaths for the UDP^1^ by Substance Using Starting
Doses Based on the NHK NRU Test Method for the RC Rat-Only Weight
Regression Excluding Substances with Specific Mechanisms of
Toxicity^2^**, Dose-Response Slope = 2

  -----------------------------------------------------------------------------------------------------------------------------------------------------
  **Substance**           **Reference   **IC~50~      **NRU         **NRU          **Predicted    **#Animals   **#Animals      **#Animals   **\#
                          LD~50~        (g/mL)**      Predicted     Predicted      Starting Dose  Used for     Used for        Dead for     Animals
                          (mg/kg)**                   LD~50~        Starting Dose  -- Default     Predicted    Default         Predicted    Dead for
                                                      (mg/kg)**     (mg/kg)^3^**   Starting Dose  Starting     Starting        Starting     Default
                                                                                   (mg/kg)^4^**   Dose^5^**    Dose^5^**       Dose^5^**    Starting
                                                                                                                                            Dose^5^**
  ----------------------- ------------- ------------- ------------- -------------- -------------- ------------ ------------ -- ------------ -----------
  ***LD~50~ ≤ 5 mg/kg***                                                                                                                    

  Cycloheximide           2             0.09          62.83         55             -120           10.04        11.70           6.38         7.83

  Phenylthiourea          3             347.23        1251.39       550            375            12.15        10.77           8.24         7.07

  Sodium selenate         3             10.97         361.14        175            0              11.88        11.78           8.27         8.16

  Triethylene-melamine    4             1.97          196.62        175            0              12.09        12.25           9.02         9.14

  **Category Mean**       **3.00**      **90.07**     **468**       **238.75**     **63.75**      **11.54**    **11.63**       **7.98**     **8.05**

  ***5 \< LD~50~ ≤ 50                                                                                                                       
  mg/kg***                                                                                                                                  

  Aminopterin             7             687.45        1596.0        550            375            12.32        10.79           8.42         7.06

  Busulfan                12            280.95        1149.13       550            375            12.57        11.41           8.82         7.73

  Thallium I sulfate      25            0.16          80.63         55             -120           7.89         9.31            4.12         5.21

  Arsenic III trioxide    25            8.95          303.68        175            0              9.33         9.41            5.42         5.48

  Digoxin                 28            0.02          18.98         17.5           -157.5         8.19         10.13           3.86         5.83

  Mercury II chloride     40            5.91          293.91        175            0              12.25        12.18           9.15         9.17

  Sodium arsenite         44            0.53          121.57        55             -120           7.74         8.66            3.98         4.72

  **Category Mean**       **25.86**     **140.57**    **509.13**    **225.36**     **50.36**      **10.04**    **10.27**       **6.25**     **6.46**

  ***50 \< LD~50~ ≤ 300                                                                                                                     
  mg/kg***                                                                                                                                  

  Sodium dichromate       51            0.76          140.27        55             -120           7.68         8.48            3.91         4.57
  dihydrate                                                                                                                                 

  Hexachlorophene         82            0.03          44.58         17.5           -157.5         8.70         8.43            4.08         4.45

  Sodium I fluoride       127           50.36         632.08        550            375            8.33         7.66            4.42         3.88

  Cadmium II chloride     135           2.12          198.67        175            0              7.60         7.70            3.92         4.01

  Diquat dibromide        160           4.90          270.19        175            0              7.26         7.30            3.56         3.59

  **Category Mean**       **111.00**    **11.63**     **257.16**    **194.5**      **19.5**       **7.91**     **7.91**        **3.98**     **4.1**

                                                                                                                                            

                                                                                                                                            

  ***300 \< LD~50~ ≤ 2000                                                                                                                   
  mg/kg***                                                                                                                                  

  Triphenyltin hydroxide  329           0.01          31.52         17.5           -157.5         8.34         8.90            3.97         4.79

  Propranolol HCl         466           36.24         560.03        550            375            7.83         8.05            3.80         3.79

  Cupric sulfate \* 5 H2O 474           197.23        1029.78       550            375            7.74         7.70            3.96         3.77

  Phenol                  548           77.49         730.37        550            375            7.69         7.94            3.85         3.81

  Lithium carbonate       590           481.51        1409.33       550            375            7.92         9.43            3.71         4.06

  Sodium oxalate          633           362.13        1258.35       550            375            8.61         7.65            4.65         3.90

  Valproic acid           995           539.79        1460.19       550            375            8.17         10.03           3.66         4.10

  Meprobamate             1387          705.09        1389.68       550            375            7.88         8.88            3.87         4.00

  Acetylsalicylic acid    1506          615.35        1540.77       550            375            7.78         9.29            3.70         4.08

  **Category Mean**       **769.78**    **334.98**    **1045.56**   **490.83**     **315.83**     **8**        **8.65**        **3.91**     **4.03**

  ***2000 \< LD~50~ ≤                                                                                                                       
  5000 mg/kg***                                                                                                                             

  Acetaminophen           2163          524.17        1455.08       550            375            8.79         10.41           3.67         3.97

  Potassium I chloride    2799          2267.61       2450.4        1750           1575           7.71         10.72           3.46         4.02

  Boric aid               3426          485.85        1367.24       550            375            8.94         10.48           3.67         3.86

  5-Aminosalicylic acid   3429          52.42         625.78        550            375            9.60         10.22           2.11         2.05

  Chloramphenicol         3491          376.83        1276.58       550            375            9.50         10.83           3.58         3.71

  Acetonitrile            3598          10220.29      4153.09       1750           1575           8.05         11.16           3.36         3.61

  Lactic acid             3639          1308.40       2022.67       1750           1575           8.51         10.96           3.42         3.59

  Sodium chloride         4046          3429.18       2491.75       1750           1575           8.35         10.82           3.55         3.86

  Xylene                  4667          496.67        1412.29       550            375            10.09        11.09           3.41         3.38

  **Category Mean**       **3473.11**   **2129.05**   **1917.21**   **1083.33**    **908.33**     **8.84**     **10.74**       **3.36**     **3.56**

  ***LD~50~ \> 5000                                                                                                                         
  mg/kg***                                                                                                                                  

  2-Propanol              5105          5551.05       3358.49       1750           1575           8.88         10.52           2.78         2.81

  Trichloroacetic acid    5229          428.55        1347.75       550            375            10.11        11.06           3.16         3.11

  Dimethylform-amide      5309          7903.49       3831.05       1750           1575           7.75         10.75           3.48         3.93

  Citric Acid             5929          413.81        1331.31       550            375            9.44         10.73           3.72         3.81

  Gibberellic acid        6040          2876.57       2677.55       1750           1575           8.84         10.81           2.62         2.64

  Ethylene glycol         7161          42203.55      6964.53       5000           4825           7.23         9.93            1.87         1.84

  Dibutylphthalate        8892          31.75         523.33        175            0              8.51         8.84            1.17         1.19

  Diethylphthalate        9311          160.59        895.93        550            375            9.09         9.90            1.86         1.85

  Sodium hypochlorite     10328         1597.68       2141.25       1750           1575           7.99         9.78            1.79         1.76

  Ethanol                 11324         10217.12      4194.11       1750           1575           5.39         8.23            0.83         0.89

  1,1,1-Trichloroethane   12078         8130.28       3879.88       1750           1575           7.40         9.18            1.48         1.39

  Glycerol                19770         28156.87      5880.49       5000           4825           5.61         8.55            1.01         1.03

  Methanol                8710          1634.79       2158.26       1750           1575           6.70         8.43            1.03         0.97

  **Category Mean**       **8873.00**   **8408.16**   **3014.15**   **1851.92**    **1676.92**    **7.92**     **9.75**        **2.06**     **2.09**
  -----------------------------------------------------------------------------------------------------------------------------------------------------

^1^OECD (2001a); EPA (2002a).

^2^RC Rat-only weight regression excluding substances with specific
mechanisms of toxicity is log LD~50~ (mg/kg) = 0.357 log IC~50~ (g/mL) +
2.194.

^3^Starting dose was one default dose lower than the predicted LD~50~
calculated using the geometric mean of the laboratory geometric mean NHK
NRU IC~50~ values in the RC Rat-only weight regression excluding
substances with specific mechanisms of toxicity.

^4^Default starting dose = 175 mg/kg.

^5^Numbers are mean numbers of animals for 2000 simulations for each
substance with a limit dose of 5000 mg/kg. Although the simulations used
whole animals, averaging the results produced fractional numbers of
animals. Results are provided for 47 substances in the NHK NRU test
method categorized using the reference LD~50~ values from **Table 4-2**.

**Table 5 Animal Use/Deaths for the ATC Method^1^ by Substance Using
Starting Doses Based on the 3T3 NRU Test Method with the RC Millimole
Regression^2^**, Dose-Response Slope = 2

  ------------------------------------------------------------------------------------------------------------------------------------
  **Substance**           **Reference   **NRU         **NRU          **Predicted    **#Animals   **#Animals   **#Animals   **\#
                          LD~50~        Predicted     Predicted      Starting Dose  Used for     Used for     Dead for     Animals
                          (mg/kg)**     LD~50~        Starting Dose  -- Default     Predicted    Default      Predicted    Dead for
                                        (mg/kg)**     (mg/kg)^3^**   Starting Dose  Starting     Starting     Starting     Default
                                                                     (mg/kg)^4^**   Dose^5^**    Dose^5^**    Dose^5^**    Starting
                                                                                                                           Dose^5^**
  ----------------------- ------------- ------------- -------------- -------------- ------------ ------------ ------------ -----------
  ***LD~50~ ≤ 5 mg/kg***                                                                                                   

  Mercury II chloride     1             186.79        50             -250           6.06         9.04         5.8          8.8

  Triethylenemelamine     1             57.08         50             -250           4.45         9.05         4.22         8.82

  Sodium selenate         2             365.3         300            0              8.32         9.21         7.82         8.69

  Cycloheximide           2             53.46         50             -250           4.86         9.35         4.1          8.63

  Busulfan                2             714.42        300            0              9.19         9.3          8.47         8.62

  Aminopterin             3             14.78         5              -295           4.01         9.77         2.75         8.51

  Phenylthiourea          3             543.89        300            0              9.27         9.72         8.04         8.51

  **Category Mean**       **1.94**      **276.53**    **150.71**     **-149.29**    **6.59**     **9.35**     **5.89**     **8.65**

  ***5 \< LD~50~ ≤ 50                                                                                                      
  mg/kg***                                                                                                                 

  Digoxin                 18            2723.4        2000           1700           14.64        12.11        8.98         6.44

  Arsenic III trioxide    20            116.81        50             -250           9.19         12.11        3.35         6.31

  Thallium I sulfate      29            321.41        300            0              10.93        12.34        4.44         5.84

  Sodium arsenite         41            60.03         50             -250           9.99         12.34        3.02         5.47

  Triphenyltin hydroxide  44            21.99         5              -295           10.84        12.17        3.05         5.38

  Sodium dichromate       50            84.19         50             -250           9.75         11.91        3.08         5.18
  dihydrate                                                                                                                

  **Category Mean**       **33.63**     **554.64**    **409.17**     **109.17**     **10.89**    **12.16**    **4.32**     **5.77**

  ***50 \< LD~50~ ≤ 300                                                                                                    
  mg/kg***                                                                                                                 

  Hexachlorophene         61            236.33        50             -250           9.87         11.63        3.23         4.93

  Cadmium II chloride     88            61.1          50             -250           10.21        10.89        3.31         4.4

  Sodium oxalate          155           331.76        300            0              10           10.01        3.46         3.65

  Sodium fluoride         180           232.67        50             -250           9.99         9.91         3.2          3.45

  Diquat dibromide        243           323.78        300            0              10.25        9.87         3.24         3.3

  Cupric sulfate \* 5 H2O 300           592.61        300            0              10.14        9.81         3.25         3.21

  **Category Mean**       **171.21**    **296.38**    **175.00**     **-125.00**    **10.08**    **10.35**    **3.28**     **3.82**

                                                                                                                           

  ***300 \< LD~5~0 ≤ 2000                                                                                                  
  mg/kg***                                                                                                                 

  Phenol                  414           345.71        300            0              10.35        9.69         3.29         3.26

  Propranolol HCl         470           332.72        300            0              10.54        9.68         3.36         3.31

  Meprobamate             794           1380.41       300            0              9.56         9.57         3.26         3.25

  Acetylsalicylic acid    1000          1379.58       300            0              9.62         9.69         3.16         3.16

  Lithium carbonate       1187          754.01        300            0              9.78         9.83         3.05         3.03

  Valproic acid           1471          1417.67       300            0              10.25        10.26        2.76         2.69

  **Category Mean**       **889.31**    **935.02**    **300.00**     **0.00**       **10.02**    **9.79**     **3.15**     **3.12**

  ***2000 \< LD~50~ ≤                                                                                                      
  5000 mg/kg***                                                                                                            

  Acetaminophen           2404          390.66        300            0              11           10.82        2.29         2.26

  Potassium I chloride    2602          1699.25       300            0              10.79        10.91        2.15         2.2

  Boric aid               2660          1191.64       300            0              10.89        10.93        2.17         2.13

  Dimethylformamide       2800          1973.96       300            0              10.06        11.03        2.02         2.11

  Sodium chloride         2998          1671.23       300            0              11.14        11.13        1.96         1.96

  Citric Acid             3000          1537.83       300            0              10.96        11.09        1.93         1.95

  Chloramphenicol         3393          973.4         300            0              11.19        11.21        1.82         1.81

  Lactic acid             3730          1763.86       300            0              11.28        11.34        1.69         1.67

  Acetonitrile            3798          1739.42       300            0              10.76        11.37        1.61         1.66

  Xylene                  4300          1031.91       300            0              11.53        11.49        1.43         1.47

  Trichloroacetic acid    4999          1461.25       300            0              11.63        11.65        1.26         1.27

  **Category Mean**       **3334.91**   **1417.95**   **300.00**     **0.00**       **11.23**    **11.36**    **1.62**     **1.64**

  ***LD~50~ \> 5000                                                                                                        
  mg/kg***                                                                                                                 

  2-Propanol              5843          1514.94       300            0              11.73        11.73        1.07         1.07

  Gibberellic acid        6305          5681.53       2000           1700           6.53         11.78        0.9          0.97

  5-Aminosalicylic acid   7749          1828.23       300            0              11.06        11.87        0.74         0.73

  Ethylene glycol         8567          3514.03       2000           1700           6.29         11.92        0.61         0.64

  Diethylphthalate        8602          689.38        300            0              11.9         11.91        0.62         0.63

  Sodium hypochlorite     8910          1048.59       300            0              11.89        11.93        0.56         0.59

  1,1,1-Trichloroethane   10298         4801.13       2000           1700           6.15         11.94        0.44         0.47

  Dibutylphthalate        11998         628.15        300            0              12.55        11.97        0.36         0.36

  Glycerol                12691         4627.7        2000           1700           6.1          11.97        0.32         0.35

  Ethanol                 14008         1681.84       300            0              11.58        11.98        0.28         0.27

  **Category Mean**       **9497.17**   **2601.55**   **980.00**     **680.00**     **9.58**     **11.90**    **0.59**     **0.61**
  ------------------------------------------------------------------------------------------------------------------------------------

^1^OECD (2001d).

^2^RC millimole regression is log LD~50~ (mmol/kg) = 0.435 log IC~50~
(mM) + 0.625.

^3^Starting dose was one was one fixed dose lower than the predicted
LD~50~ calculated using the geometric mean of the laboratory geometric
mean 3T3 NRU IC~50~ values in the RC millimole regression.

^4^Default starting dose = 300 mg/kg.

^5^Numbers are mean numbers of animals for 2000 simulations for each
substance with a limit dose of 2000 mg/kg. Although the simulations used
whole animals, averaging the results produced fractional numbers of
animals. Results are provided for 46 substances in the 3T3 NRU test
method categorized using the initial LD~50~ values from **Table 3-2**.

**Table 6 Animal Use/Deaths for the ATC Method^1^ by Substance Using
Starting Doses Based on the NHK NRU Test Method with the RC Millimole
Regression^2^**, Dose-Response Slope = 2

  -----------------------------------------------------------------------------------------------------------------------------------------------------------------
  **Substance**           **Reference       **NRU            **NRU          **Predicted            **#Animals      **#Animals   **#Animals              **\#
                          LD~50~            Predicted        Predicted      Starting Dose          Used for        Used for     Dead for                Animals
                          (mg/kg)**         LD~50~           Starting Dose  -- Default             Predicted       Default      Predicted               Dead for
                                            (mg/kg)**        (mg/kg)^3^**   Starting Dose          Starting        Starting     Starting                Default
                                                                            (mg/kg)^4^**           Dose^5^**       Dose^5^**    Dose^5^**               Starting
                                                                                                                                                        Dose^5^**
  ----------------------- -------------- -- ------------- -- -------------- -------------- ------- ------------ -- ------------ ------------ ------- -- -----------
  ***LD~50~ ≤ 5 mg/kg***                                                                                                                                

  Mercury II chloride     1                 215.22           50             -250                   6.05            9.05         5.8                     8.81

  Triethylenemelamine     1                 113.09           50             -250                   6.06            9.08         5.81                    8.81

  Sodium selenate         2                 226.45           50             -250                   6.35            9.21         5.83                    8.71

  Cycloheximide           2                 33.73            5              -295                   3.52            9.35         2.8                     8.63

  Busulfan                2                 1076.73          300            0                      9.33            9.34         8.62                    8.64

  Aminopterin             3                 2244.41          2000           1700                   12.27           9.75         10.97                   8.49

  Phenylthiourea          3                 910.37           300            0                      9.73            9.82         8.49                    8.52

  **Category Mean**       **1.94**          **688.57**       **393.57**     **93.57**              **7.62**        **9.37**     **6.90**                **8.66**

  ***5 \< LD~50~ ≤ 50                                                                                                                                   
  mg/kg***                                                                                                                                              

  Digoxin                 18                14.67            5              -295                   8.85            12.08        3.24                    6.4

  Arsenic III trioxide    20                188.1            50             -250                   9.49            12.14        3.69                    6.3

  Thallium I sulfate      29                63               50             -250                   9.49            12.29        3.03                    5.8

  Sodium arsenite         41                49.16            5              -250                   10.2            12.24        3.01                    5.44

  Triphenyltin hydroxide  44                17.19            5              -295                   10.81           12.23        3.04                    5.35

  Sodium dichromate       50                91.94            50             -250                   9.76            12.04        3.05                    5.19
  dihydrate                                                                                                                                             

  **Category Mean**       **33.63**         **70.68**        **27.50**      **-265.00**            **9.77**        **12.17**    **3.18**                **5.75**

  ***50 \< LD~50~ ≤                                                                                                                                     
  300*** ***mg/kg***                                                                                                                                    

  Hexachlorophene         61                27.45            5              -295                   12.01           11.66        3.24                    4.93

  Cadmium II chloride     88                107.13           50             -250                   9.66            10.99        3.3                     4.41

  Sodium oxalate          155               852.28           300            0                      10.08           9.99         3.61                    3.57

  Sodium fluoride         180               190.72           50             -250                   9.95            9.92         3.21                    3.41

  Diquat dibromide        243               231.57           50             -250                   10.45           9.91         3.24                    3.28

  Cupric sulfate \* 5 H2O 300               948.71           300            0                      9.81            9.84         3.21                    3.19

  **Category Mean**       **171.21**        **392.98**       **125.83**     **-174.17**            **10.33**       **10.39**    **3.30**                **3.80**

                                                                                                                                                        

  ***300 \< LD~50~ ≤ 2000                                                                                                                               
  mg/kg***                                                                                                                                              

  Phenol                  414               360.99           300            0                      9.96            9.73         3.3                     3.29

  Propranolol HCl         470               497.79           300            0                      9.66            9.69         3.26                    3.27

  Meprobamate             794               1297.2           300            0                      9.63            9.56         3.31                    3.23

  Acetylsalicylic acid    1000              1289.52          300            0                      9.64            9.68         3.12                    3.17

  Lithium carbonate       1187              697.3            300            0                      9.77            9.79         3.02                    3.04

  Valproic acid           1471              1069.47          300            0                      10.23           10.24        2.7                     2.71

  **Category Mean**       **889.31**        **868.71**       **300.00**     **0.00**               **9.82**        **9.78**     **3.12**                **3.12**

  ***2000 \< LD~5~0 ≤                                                                                                                                   
  5000 mg/kg***                                                                                                                                         

  Acetaminophen           2404              1091.611         300            0                      10.85           10.76        2.29                    2.33

  Potassium I chloride    2602              1385.81          300            0                      10.87           10.92        2.17                    2.18

  Boric aid               2660              621.39           300            0                      10.86           10.94        2.14                    2.13

  Dimethylformamide       2800              2354.11          2000           1700                   8.37            10.93        2.03                    2.07

  Sodium chloride         2998              1283.1           300            0                      10.86           11.11        2.01                    1.98

  Citric Acid             3000              1122.63          300            0                      11.1            11.1         2                       2.01

  Chloramphenicol         3393              1433.01          300            0                      11.13           11.29        1.79                    1.78

  Lactic acid             3730              1215.16          300            0                      11.35           11.39        1.69                    1.63

  Acetonitrile            3798              1863.4           300            0                      10.31           11.43        1.59                    1.62

  Xylene                  4300              859.04           300            0                      11.53           11.54        1.47                    1.44

  Trichloroacetic acid    4999              1039.5           300            0                      11.65           11.66        1.25                    1.2

  **Category Mean**       **3334.91**       **1255.46**      **300.00**     **0.00**               **11.18**       **11.40**    **1.63**                **1.61**

  ***LD~50~ \> 5000                                                                                                                                     
  mg/kg***                                                                                                                                              

  2-Propanol              5843              1794.19          300            0                      10.94           11.8         1.04                    1.04

  Gibberellic acid        6305              3659.71          2000           1700                   6.59            11.82        0.94                    0.93

  5-Aminosalicylic acid   7749              392.57           300            0                      12.63           11.88        0.71                    0.74

  Ethylene glycol         8567              4464.95          2000           1700                   6.21            11.9         0.57                    0.65

  Diethylphthalate        8602              748.97           300            0                      12              11.92        0.03                    0.63

  Sodium hypochlorite     8910              1165.71          300            0                      11.91           11.94        0.57                    0.58

  1,1,1-Trichloroethane   10298             3360.96          2000           1700                   6.15            11.96        0.45                    0.45

  Dibutylphthalate        11998             450.15           300            0                      12.19           11.98        0.36                    0.36

  Glycerol                12691             4539.08          2000           1700                   6.08            11.97        0.33                    0.33

  **Category Mean**       **10214.07**      **2154.84**      **1150.00**    **850.00**             **9.45**        **11.93**    **0.46**                **0.53**
  -----------------------------------------------------------------------------------------------------------------------------------------------------------------

^1^OECD (2001d).

^2^RC millimole regression is log LD~50~ (mmol/kg) = 0.435 log IC~50~
(mM) + 0.625.

^3^Starting dose was one was one fixed dose lower than the predicted
LD~50~ calculated using the geometric mean of the laboratory geometric
mean NHK NRU IC~50~ values in the RC millimole regression.

^4^Default starting dose = 300 mg/kg.

^5^Numbers are mean numbers of animals for 2000 simulations for each
substance with a limit dose of 2000 mg/kg. Although the simulations used
whole animals, averaging the results produced fractional numbers of
animals. Results are provided for 47 substances in the NHK NRU test
method categorized using the initial LD~50~ values from **Table 3-2**.

**Table 7 Animal Use/Deaths^1^ for the ATC Method^2^ by Substance^3^
Using Starting Doses Based on the 3T3 NRU Test Method for the RC
Rat-Only Weight Regression Excluding Substances with Specific Mechanisms
of Toxicity^4^**, Dose-Response Slope = 2

  ----------------------------------------------------------------------------------------------------------------------------------------------
  **Substance**           **Reference   **NRU         **NRU          **Predicted    **#Animals   **#Animals             **#Animals   **\#
                          LD~50~        Predicted     Predicted      Starting Dose  Used for     Used for               Dead for     Animals
                          (mg/kg)**     LD~50~        Starting Dose  -- Default     Predicted    Default                Predicted    Dead for
                                        (mg/kg)**     (mg/kg)^3^**   Starting Dose  Starting     Starting               Starting     Default
                                                                     (mg/kg)^4^**   Dose^5^**    Dose^5^**              Dose^5^**    Starting
                                                                                                                                     Dose^5^**
  ----------------------- ------------- ------------- -------------- -------------- ------------ ------------ --------- ------------ -----------
  ***LD~50~ ≤ 5 mg/kg***                                                                                                             

  Cycloheximide           2             90.79         50             -250           6.21         9.35                   5.48         8.63

  Phenylthiourea          3             804.25        300            0              9.79         9.72                   8.53         8.51

  Sodium selenate         3             532.67        300            0              9.20         9.21                   8.65         8.69

  Triethylene-melamine    4             109.1         50             -250           5.87         9.05                   5.63         8.82

  **Category Mean**       **3.00**      **384.2**     **175**        **-125**       **7.77**     **9.33**               **7.07**     **8.66**

  ***5 \< LD~50~ ≤ 50                                                                                                                
  mg/kg***                                                                                                                           

  Aminopterin             7             25.92         5              -295           4.00         9.77                   2.73         8.51

  Busulfan                12            784.63        300            0              9.29         9.30                   8.60         8.62

  Thallium I sulfate      25            304.29        300            0              10.82        12.34                  4.37         5.84

  Arsenic III trioxide    25            204.86        50             -250           9.29         12.11                  3.47         6.31

  Digoxin                 28            1412.18       300            0              12.19        12.11                  6.53         6.44

  Mercury II chloride     40            261.10        50             -250           6.29         9.04                   6.05         8.80

  Sodium arsenite         44            145.07        50             -250           9.56         12.15                  3.94         5.98

  **Category Mean**       **25.86**     **448.9**     **150.71**     **149.29**     **8.78**     **10.97**    **5.1**                **7.21**

  ***50 \< LD~50~ ≤ 300                                                                                                              
  mg/kg***                                                                                                                           

  Sodium dichromate       51            130.18        50             -250           9.71         11.91                  3.07         5.18
  dihydrate                                                                                                                          

  Hexachlorophene         82            263.89        50             -250           10.03        11.63                  3.39         4.93

  Sodium I fluoride       127           743.55        300            0              9.97         9.91                   3.44         3.45

  Cadmium II chloride     135           125.34        50             -250           9.61         10.89                  3.28         4.40

  Diquat dibromide        160           359.03        300            0              10.12        9.87                   3.25         3.30

  **Category Mean**       **111.00**    **324.4**     **150**        **-150**       **9.89**     **10.84**              **3.29**     **4.25**

                                                                                                                                     

                                                                                                                                     

  ***300 \< LD~50~ ≤ 2000                                                                                                            
  mg/kg***                                                                                                                           

  Triphenyltin hydroxide  329           38.57         5              -295           10.58        12.17                  3.00         5.38

  Propranolol HCl         466           402.28        300            0              9.70         9.68                   3.35         3.31

  Cupric sulfate \* 5 H2O 474           680.25        300            0              9.96         9.81                   3.28         3.21

  Phenol                  548           707.62        300            0              9.71         9.69                   3.24         3.26

  Lithium carbonate       590           1499.37       300            0              9.75         9.83                   3.03         3.03

  Sodium oxalate          633           581.40        300            0              10.08        10.01                  3.59         3.65

  Valproic acid           995           1820.48       300            0              10.04        10.26                  2.70         2.69

  Meprobamate             1387          1471.54       300            0              9.53         9.57                   3.29         3.25

  Acetylsalicylic acid    1506          1624.35       300            0              9.66         9.69                   3.19         3.16

  **Category Mean**       **769.78**    **980.65**    **267.22**     **-32.78**     **9.89**     **10.08**              **3.19**     **3.44**

  ***2000 \< LD~50~ ≤                                                                                                                
  5000 mg/kg***                                                                                                                      

  Acetaminophen           2163          625.12        300            0              10.74        10.82                  2.27         2.26

  Potassium I chloride    2799          2900.86       2000           1700           8.45         10.91                  2.09         2.20

  Boric aid               3426          2363.90       2000           1700           9.10         10.93                  2.11         2.13

  5-Aminosalicylic acid   3429          2209.04       2000           1700           6.81         0.73                   11.87        0.73

  Chloramphenicol         3491          914.40        300            0              11.26        11.21                  1.85         1.81

  Acetonitrile            3598          3910.34       2000           1700           7.56         11.37                  1.61         1.66

  Lactic acid             3639          2744.30       2000           1700           7.61         11.34                  1.62         1.67

  Sodium chloride         4046          3198.68       2000           1700           8.18         11.13                  1.91         1.96

  Xylene                  4667          1636.98       300            0              11\. 50      11.49                  1.46         1.47

  **Category Mean**       **3473.11**   **2278.18**   **1433.33**    **1133.33**    **14.52**    **9.99**               **2.98**     **1.77**

  ***LD~50~ \> 5000                                                                                                                  
  mg/kg***                                                                                                                           

  2-Propanol              5105          2919.81       2000           1700           6.67         11.73                  1.01         1.07

  Trichloroacetic acid    5229          1784.60       300            0              11.19        11.65                  1.22         1.27

  Dimethylform-amide      5309          3318.52       2000           1700           8.31         11.03                  2.02         2.11

  Citric Acid             5929          1717.29       300            0              10.62        11.09                  1.99         1.95

  Gibberellic acid        6040          3829.60       2000           1700           6.58         11.78                  0.92         0.97

  Ethylene glycol         7161          5788.53       2000           1700           6.23         11.92                  0.60         0.62

  Dibutylphthalate        8892          682.02        300            0              12.11        11.97                  0.36         0.36

  Diethylphthalate        9311          832.66        300            0              11.93        11.91                  0.62         0.63

  Sodium hypochlorite     10328         1946.41       300            0              9.62         11.93                  0.55         0.59

  Ethanol                 11324         3594.39       2000           1700           6.06         11.98                  0.29         0.27

  1,1,1-Trichloroethane   12078         5179.85       2000           1700           6.15         11.94                  0.44         0.47

  Glycerol                19770         5942.72       2000           1700           6.09         11.97                  0.33         0.35

  **Category Mean**       **8873.00**   **3128.03**   **1291.67**    **991.67**     **8.46**     **11.74**              **0.86**     **0.89**
  ----------------------------------------------------------------------------------------------------------------------------------------------

^1^OECD (2001d).

^2^RC Rat-only weight regression excluding substances with specific
mechanisms of toxicity is log LD~50~ (mg/kg) = 0.357 log IC~50~ (g/mL) +
2.194.

^3^Starting dose was one fixed dose lower than the predicted LD~50~
calculated using the geometric mean of the laboratory geometric mean 3T3
NRU IC~50~ values in RC Rat-only weight regression excluding substances
with specific mechanisms of toxicity.

^4^Default starting dose = 300 mg/kg.

^5^Numbers are mean numbers of animals for 2000 simulations for each
substance with a limit dose of 2000 mg/kg. Although the simulations used
whole animals, averaging the results produced fractional numbers of
animals. Results are provided for 46 substances in the 3T3 NRU test
method categorized using the reference LD~50~ values from **Table 4-2**.

**Table 8 Animal Use/Deaths for the ATC Method^1^ by Substance Using
Starting Doses Based on the NHK NRU Test Method for the RC Rat-Only
Weight Regression Excluding Substances with Specific Mechanisms of
Toxicity^2^**, Dose-Response Slope = 2

  ---------------------------------------------------------------------------------------------------------------------------------------
  **Substance**           **Reference   **NRU         **NRU          **Predicted    **#Animals   **#Animals      **#Animals   **\#
                          LD~50~        Predicted     Predicted      Starting Dose  Used for     Used for        Dead for     Animals
                          (mg/kg)**     LD~50~        Starting Dose  -- Default     Predicted    Default         Predicted    Dead for
                                        (mg/kg)**     (mg/kg)^3^**   Starting Dose  Starting     Starting        Starting     Default
                                                                     (mg/kg)^4^**   Dose^5^**    Dose^5^**       Dose^5^**    Starting
                                                                                                                              Dose^5^**
  ----------------------- ------------- ------------- -------------- -------------- ------------ ------------ -- ------------ -----------
  ***LD~50~ ≤ 5 mg/kg***                                                                                                      

  Cycloheximide           2             62.44         50             -250           5.88         5.19            9.35         8.63

  Phenylthiourea          3             1253.69       300            0              9.77         9.82            8.50         8.52

  Sodium selenate         3             360.69        300            0              8.87         9.21            8.36         8.71

  Triethylene-melamine    4             196.58        50             -250           6.04         5.80            9.08         8.81

  **Category Mean**       **3.00**      **468.35**    **175**        **-125**       **7.64**     **7.51**        **8.82**     **8.67**

  ***5 \< LD~50~ ≤ 50                                                                                                         
  mg/kg***                                                                                                                    

  Aminopterin             7             1597.68       300            0              9.73         9.75            8.51         8.48

  Busulfan                12            1147.41       300            0              9.37         9.34            8.64         8.64

  Thallium I sulfate      25            80.19         50             -250           9.54         12.29           3.06         5.80

  Arsenic III trioxide    25            305.56        300            0              10.50        12.14           4.61         6.30

  Digoxin                 28            18.27         5              -295           8.90         12.08           3.25         6.40

  Mercury II chloride     40            293.29        50             -250           7.08         9.05            6.82         8.81

  Sodium arsenite         44            122.88        50             -250           9.68         12.24           3.03         5.44

  **Category Mean**       **25.86**     **509.33**    **150.71**     **-149.29**    **9.26**     **10.98**       **5.42**     **7.12**

  ***50 \< LD~50~ ≤ 300                                                                                                       
  mg/kg***                                                                                                                    

  Sodium dichromate       51            140.07        50             -250           9.72         12.04           3.07         5.19
  dihydrate                                                                                                                   

  Hexachlorophene         82            44.62         5              -295           11.35        11.66           3.14         4.93

  Sodium I fluoride       127           632.45        300            0              9.91         9.92            3.45         3.41

  Cadmium II chloride     135           196.93        50             -250           9.60         10.99           3.25         4.41

  Diquat dibromide        160           270.49        50             -250           10.43        9.91            3.24         3.28

  **Category Mean**       **111.00**    **256.91**    **91**         **-209**       **10.2**     **10.9**        **3.23**     **4.24**

                                                                                                                              

                                                                                                                              

  ***300 \< LD~50~ ≤ 2000                                                                                                     
  mg/kg***                                                                                                                    

  Triphenyltin hydroxide  329           32.24         5              -295           10.72        3.01            12.23        5.35

  Propranolol HCl         466           558.53        300            0              9.64         9.69            3.33         3.27

  Cupric sulfate \* 5 H2O 474           1030.49       300            0              9.82         9.84            3.22         3.19

  Phenol                  548           735.92        300            0              9.67         9.73            3.27         3.29

  Lithium carbonate       590           1407.83       300            0              9.86         9.79            3.03         3.04

  Sodium oxalate          633           1259.46       300            0              10.15        9.99            3.60         3.57

  Valproic acid           995           1459.05       300            0              10.23        10.24           2.73         2.71

  Meprobamate             1387          1413.3        300            0              9.56         9.67            3.35         3.23

  Acetylsalicylic acid    1506          1540.99       300            0              9.66         9.68            3.16         3.17

  **Category Mean**       **769.78**    **1048.65**   **267.22**     **-32.78**     **9.92**     **9.07**        **4.21**     **3.42**

  ***2000 \< LD~50~ ≤                                                                                                         
  5000 mg/kg***                                                                                                               

  Acetaminophen           2163          1457.99       300            0              10.82        10.76           0.33         0.33

  Potassium I chloride    2799          2448.66       2000           1700           8.46         10.92           2.08         2.18

  Boric aid               3426          1382.48       300            0              10.85        10.94           2.13         2.13

  5-Aminosalicylic acid   3429          624.02        300            0              11.89        11.88           0.72         0.74

  Chloramphenicol         3491          1268.48       300            0              11.29        11.29           1.81         1.78

  Acetonitrile            3598          4134.15       2000           1700           7.56         11.43           1.59         1.62

  Lactic acid             3639          2021.97       2000           1700           8.77         11.39           1.63         1.63

  Sodium chloride         4046          2517.41       2000           1700           9.17         11.11           1.93         1.98

  Xylene                  4667          1407.15       300            0              11.50        11.54           1.48         1.44

  **Category Mean**       **3473.11**   **1918.03**   **1055.56**    **755.56**     **10.03**    **11.25**       **1.52**     **1.54**

  ***LD~50~ \> 5000                                                                                                           
  mg/kg***                                                                                                                    

  2-Propanol              5105          3352.78       2000           1700           6.67         1.01            11.80        1.04

  Trichloroacetic acid    5229          1345.43       300            0              11.63        11.66           1.27         1.20

  Dimethylform-amide      5309          3820.55       2000           1700           8.40         10.93           2.04         2.07

  Citric Acid             5929          1332.25       300            0              11.06        11.10           0.31         0.31

  Gibberellic acid        6040          2673.29       2000           1700           6.57         11.82           0.89         0.93

  Ethylene glycol         7161          6974.95       2000           1700           6.25         0.60            11.90        0.65

  Dibutylphthalate        8892          523.35        300            0              11.97        11.98           0.37         0.36

  Diethylphthalate        9311          902.45        300            0              11.91        11.93           0.60         0.59

  Sodium hypochlorite     10328         2149.56       2000           1700           7.97         11.94           0.57         0.58

  Ethanol                 11324         4199.00       2000           1700           6.05         11.98           0.26         0.29

  1,1,1-Trichloroethane   12078         3880.88       2000           1700           6.15         0.45            11.96        0.45

  Glycerol                19770         5848.85       2000           1700           6.10         11.97           0.33         0.33

  Methanol                8710          2158.19       2000           1700           7.90         11.98           0.31         0.29

  **Category Mean**       **8873.00**   **3012.43**   **1476.92**    **1176.92**    **8.36**     **9.18**        **3.28**     **0.7**
  ---------------------------------------------------------------------------------------------------------------------------------------

^1^OECD (2001d).

^2^RC Rat-only weight regression excluding substances with specific
mechanisms of toxicity is log LD~50~ (mg/kg) = 0.357 log IC~50~ (g/mL) +
2.194

^3^Starting dose was one fixed dose lower than the predicted LD~50~
calculated using the geometric mean of the laboratory geometric mean NHK
NRU IC~50~ values in the RC Rat-only weight regression excluding
substances with specific mechanisms of toxicity.

^4^Default starting dose = 300 mg/kg.

^5^Numbers are mean numbers of animals for 2000 simulations for each
substance with a limit dose of 2000 mg/kg. Although the simulations used
whole animals, averaging the results produced fractional numbers of
animals. Results are provided for 47 substances in the NHK NRU test
method categorized using the reference LD~50~ values from **Table 4-2**.