Harlan Study Number: 41205015 Report 

Appendix 1 ( continued) Individual Daily Clinical Observations 

Day Numbers Relative to Start Date 

(continued) 

Group Animal 

(Sex) Number Clinical Sign 

1(F) 13 No Abnormalities Detected 

Scheduled kill 

14 No Abnormalities Detected 

Scheduled kill 

15 No Abnormalities Detected 

Scheduled kill 

16 No Abnormalities Detected 

Scheduled kill 

17 No Abnormalities Detected 

Scheduled kill 

18 No Abnormalities Detected 

Scheduled kill 

19 No Abnormalities Detected 

Scheduled kill 

20 No Abnormalities Detected 

Scheduled kill 

21 No Abnormalities Detected 

Scheduled kill 

22 No Abnormalities Detected 

Scheduled kill 

23 No Abnormalities Detected 

Scheduled kill 

24 No Abnormalities Detected 

Littering 

X = Present 

Not Observed Due to Littering Scheduled kill 

52 

1h 

52 

5h 

53 

A.M. 

53 

Pre 

53 

Post 

53 

1h 

Dose Levels: Group 1 - o (Control) Group 2 - 50 mg/kg bw/day Group 3 - 250 mg/kg bw/day 

54 

A.M. 

Group 4 - 750 mg/kg bw/day 

Page 148 
Harlan Study Number: 41205015 Report Page 149 

Appendix 1 ( continued) Individual Daily Clinical Observations 

Day Numbers Relative to Start Date 

Group Animal 1 1 1 1 2 2 2 2 3 3 3 3 4 4 4 

(Sex) Number Clinical Sign Pre Post 1h 5h Pre Post 1h 5h Pre Post 1h 5h Pre Post 1h 

2(F) 37 No Abnormalities Detected x x x x x x x x x x x x x x x 

Scheduled kill 

38 No Abnormalities Detected x x x x x x x x x x x x x x x 

Scheduled kill 

39 No Abnormalities Detected x x x x x x x x x x x x x x x 

Scheduled kill 

40 No Abnormalities Detected x x x x x x x x x x x x x x x 

Scheduled kill 

41 No Abnormalities Detected x x x x x x x x x x x x x x x 

Scheduled kill 

42 No Abnormalities Detected x x x x x x x x x x x x x x x 

Scheduled kill 

43 No Abnormalities Detected x x x x x x x x x x x x x x x 

Scheduled kill 

44 No Abnormalities Detected x x x x x x x x x x x x x x x 

Scheduled kill 

45 No Abnormalities Detected x x x x x x x x x x x x x x x 

Scheduled kill 

46 No Abnormalities Detected x x x x x x x x x x x x x x x 

Scheduled kill 

47 No Abnormalities Detected x x x x x x x x x x x x x x x 

Scheduled kill 

48 No Abnormalities Detected x x x x x x x x x x x x x x x 

Scheduled kill 

X = Present 

Dose Levels: Group 1 - O (Control) Group 2 - 50 mg/kg bw/day Group 3 - 250 mg/kg bw/day Group 4 - 750 mg/kg bw/day 
Harlan Study Number: 41205015 Report Page 150 

Appendix 1 ( continued) Individual Daily Clinical Observations 

Day Numbers Relative to Start Date 

(continued) 

Group Animal 5 5 5 6 6 6 6 7 7 7 7 8 8 8 8 

(Sex) Number Clinical Sign Pre Post 1h Pre Post 1h Sh Pre Post 1h Sh Pre Post 1h Sh 

2(F) 37 No Abnormalities Detected x x x x x x x x x x x x x x x 

Scheduled kill 

38 No Abnormalities Detected x x x x x x x x x x x x x x x 

Scheduled kill 

39 No Abnormalities Detected x x x x x x x x x x x x x x x 

Scheduled kill 

40 No Abnormalities Detected x x x x x x x x x x x x x x x 

Scheduled kill 

41 No Abnormalities Detected x x x x x x x x x x x x x x x 

Scheduled kill 

42 No Abnormalities Detected x x x x x x x x x x x x x x x 

Scheduled kill 

43 No Abnormalities Detected x x x x x x x x x x x x x x x 

Scheduled kill 

44 No Abnormalities Detected x x x x x x x x x x x x x x x 

Scheduled kill 

45 No Abnormalities Detected x x x x x x x x x x x x x x x 

Scheduled kill 

46 No Abnormalities Detected x x x x x x x x x x x x x x x 

Scheduled kill 

47 No Abnormalities Detected x x x x x x x x x x x x x x x 

Scheduled kill 

48 No Abnormalities Detected x x x x x x x x x x x x x x x 

Scheduled kill 

X = Present 

Dose Levels: Group 1 - O (Control) Group 2 - 50 mg/kg bw/day Group 3 - 250 mg/kg bw/day Group 4 - 750 mg/kg bw/day 
Harlan Study Number: 41205015 Report Page 151 

Appendix 1 ( continued) Individual Daily Clinical Observations 

Day Numbers Relative to Start Date 

(continued) 

Group Animal 9 9 9 9 10 10 10 10 11 11 11 12 12 12 13 

(Sex) Number Clinical Sign Pre Post 1 h 5h Pre Post 1h 5h Pre Post 1h Pre Post 1h Pre 

2(F) 37 No Abnormalities Detected x x x x x x x x x x x x x x x 

Scheduled kill 

38 No Abnormalities Detected x x x x x x x x x x x x x x x 

Scheduled kill 

39 No Abnormalities Detected x x x x x x x x x x x x x x x 

Scheduled kill 

40 No Abnormalities Detected x x x x x x x x x x x x x x x 

Scheduled kill 

41 No Abnormalities Detected x x x x x x x x x x x x x x x 

Scheduled kill 

42 No Abnormalities Detected x x x x x x x x x x x x x x x 

Scheduled kill 

43 No Abnormalities Detected x x x x x x x x x x x x x x x 

Scheduled kill 

44 No Abnormalities Detected x x x x x x x x x x x x x x x 

Scheduled kill 

45 No Abnormalities Detected x x x x x x x x x x x x x x x 

Scheduled kill 

46 No Abnormalities Detected x x x x x x x x x x x x x x x 

Scheduled kill 

47 No Abnormalities Detected x x x x x x x x x x x x x x x 

Scheduled kill 

48 No Abnormalities Detected x x x x x x x x x x x x x x x 

Scheduled kill 

X = Present 

Dose Levels: Group 1 - o (Control) Group 2 - 50 mg/kg bw/day Group 3 - 250 mg/kg bw/day Group 4 - 750 mg/kg bw/day 
Harlan Study Number: 41205015 Report Page 152 

Appendix 1 ( continued) Individual Daily Clinical Observations 

Day Numbers Relative to Start Date 

(continued) 

Group Animal 13 13 13 14 14 14 14 15 15 15 15 16 16 16 16 

(Sex) Number Clinical Sign Post 1h 5h Pre Post 1h 5h Pre Post 1h 5h Pre Post 1h 5h 

2(F) 37 No Abnormalities Detected x x x x x x x x x x x x x x x 

Scheduled kill 

38 No Abnormalities Detected x x x x x x x x x x x x x x x 

Scheduled kill 

39 No Abnormalities Detected x x x x x x x x x x x x x x x 

Scheduled kill 

40 No Abnormalities Detected x x x x x x x x x x x x x x x 

Scheduled kill 

41 No Abnormalities Detected x x x x x x x x x x x x x x x 

Scheduled kill 

42 No Abnormalities Detected x x x x x x x x x x x x x x x 

Scheduled kill 

43 No Abnormalities Detected x x x x x x x x x x x x x x x 

Scheduled kill 

44 No Abnormalities Detected x x x x x x x x x x x x x x x 

Scheduled kill 

45 No Abnormalities Detected x x x x x x x x x x x x x x x 

Scheduled kill 

46 No Abnormalities Detected x x x x x x x x x x x x x x x 

Scheduled kill 

47 No Abnormalities Detected x x x x x x x x x x x x x x x 

Scheduled kill 

48 No Abnormalities Detected x x x x x x x x x x x x x x x 

Scheduled kill 

x = Present 

Dose Levels: Group 1 - o (Control) Group 2 - 50 mg/kg bw/day Group 3 - 250 mg/kg bw/day Group 4 - 750 mg/kg bw/day 
Harlan Study Number: 41205015 Report Page 153 

Appendix 1 ( continued) Individual Daily Clinical Observations 

Day Numbers Relative to Start Date 

(continued) 

Group Animal 17 17 17 17 18 18 18 19 19 19 20 20 20 20 21 

(Sex) Number Clinical Sign Pre Post 1h 5h Pre Post 1h Pre Post 1h Pre Post 1h 5h Pre 

2(F) 37 No Abnormalities Detected x x x x x x x x x x x x x x x 

Scheduled kill 

38 No Abnormalities Detected x x x x x x x x x x x x x x x 

Scheduled kill 

39 No Abnormalities Detected x x x x x x x x x x x x x x x 

Scheduled kill 

40 No Abnormalities Detected x x x x x x x x x x x x x x x 

Scheduled kill 

41 No Abnormalities Detected x x x x x x x x x x x x x x x 

Scheduled kill 

42 No Abnormalities Detected x x x x x x x x x x x x x x x 

Scheduled kill 

43 No Abnormalities Detected x x x x x x x x x x x x x x x 

Scheduled kill 

44 No Abnormalities Detected x x x x x x x x x x x x x x x 

Scheduled kill 

45 No Abnormalities Detected x x x x x x x x x x x x x x x 

Scheduled kill 

46 No Abnormalities Detected x x x x x x x x x x x x x x x 

Scheduled kill 

47 No Abnormalities Detected x x x x x x x x x x x x x x x 

Scheduled kill 

48 No Abnormalities Detected x x x x x x x x x x x x x x x 

Scheduled kill 

X = Present 

Dose Levels: Group 1 - O (Control) Group 2 - 50 mg/kg bw/day Group 3 - 250 mg/kg bw/day Group 4 - 750 mg/kg bw/day 
Harlan Study Number: 41205015 Report Page 154 

Appendix 1 ( continued) Individual Daily Clinical Observations 

Day Numbers Relative to Start Date 

(continued) 

Group Animal 21 21 21 22 22 22 22 23 23 23 23 24 24 24 24 

(Sex) Number Clinical Sign Post 1h 5h Pre Post 1h 5h Pre Post 1h 5h Pre Post 1h 5h 

2(F) 37 No Abnormalities Detected x x x x x x x x x x x x x x x 

Scheduled kill 

38 No Abnormalities Detected x x x x x x x x x x x x x x x 

Scheduled kill 

39 No Abnormalities Detected x x x x x x x x x x x x x x x 

Scheduled kill 

40 No Abnormalities Detected x x x x x x x x x x x x x x x 

Scheduled kill 

41 No Abnormalities Detected x x x x x x x x x x x x x x x 

Scheduled kill 

42 No Abnormalities Detected x x x x x x x x x x x x x x x 

Scheduled kill 

43 No Abnormalities Detected x x x x x x x x x x x x x x x 

Scheduled kill 

44 No Abnormalities Detected x x x x x x x x x x x x x x x 

Scheduled kill 

45 No Abnormalities Detected x x x x x x x x x x x x x x x 

Scheduled kill 

46 No Abnormalities Detected x x x x x x x x x x x x x x x 

Scheduled kill 

47 No Abnormalities Detected x x x x x x x x x x x x x x x 

Scheduled kill 

48 No Abnormalities Detected x x x x x x x x x x x x x x x 

Scheduled kill 

X = Present 

Dose Levels: Group 1 - O (Control) Group 2 - 50 mg/kg bw/day Group 3 - 250 mg/kg bw/day Group 4 - 750 mg/kg bw/day 
Harlan Study Number: 41205015 Report Page 155 

Appendix 1 ( continued) Individual Daily Clinical Observations 

Day Numbers Relative to Start Date 

(continued) 

Group Animal 25 25 25 26 26 26 27 27 27 27 28 28 28 28 29 

(Sex) Number Clinical Sign Pre Post 1h Pre Post 1h Pre Post 1h 5h Pre Post 1h 5h Pre 

2(F) 37 No Abnormalities Detected x x x x x x x x x x x x x x x 

Scheduled kill 

38 No Abnormalities Detected x x x x x x x x x x x x x x x 

Scheduled kill 

39 No Abnormalities Detected x x x x x x x x x x x x x x x 

Scheduled kill 

40 No Abnormalities Detected x x x x x x x x x x x x x x x 

Scheduled kill 

41 No Abnormalities Detected x x x x x x x x x x x x x x x 

Scheduled kill 

42 No Abnormalities Detected x x x x x x x x x x x x x x x 

Scheduled kill 

43 No Abnormalities Detected x x x x x x x x x x x x x x x 

Scheduled kill 

44 No Abnormalities Detected x x x x x x x x x x x x x x x 

Scheduled kill 

45 No Abnormalities Detected x x x x x x x x x x x x x x x 

Scheduled kill 

46 No Abnormalities Detected x x x x x x x x x x x x x x x 

Scheduled kill 

47 No Abnormalities Detected x x x x x x x x x x x x x x x 

Scheduled kill 

48 No Abnormalities Detected x x x x x x x x x x x x x x x 

Scheduled kill 

X = Present 

Dose Levels: Group 1 - o (Control) Group 2 - 50 mg/kg bw/day Group 3 - 250 mg/kg bw/day Group 4 - 750 mg/kg bw/day 
Harlan Study Number: 41205015 Report Page 156 

Appendix 1 ( continued) Individual Daily Clinical Observations 

Day Numbers Relative to Start Date 

(continued) 

Group Animal 29 29 29 30 30 30 30 31 31 31 31 32 32 32 33 

(Sex) Number Clinical Sign Post 1h Sh Pre Post 1h Sh Pre Post 1h Sh Pre Post 1h Pre 

2(F) 37 No Abnormalities Detected x x x x x x x x x x x x x x x 

Scheduled kill 

38 No Abnormalities Detected x x x x x x x x x x x x x x x 

Scheduled kill 

39 No Abnormalities Detected x x x x x x x x x x x x x x x 

Scheduled kill 

40 No Abnormalities Detected x x x x x x x x x x x x x x x 

Scheduled kill 

41 No Abnormalities Detected x x x x x x x x x x x x x x x 

Scheduled kill 

42 No Abnormalities Detected x x x x x x x x x x x x x x x 

Scheduled kill 

43 No Abnormalities Detected x x x x x x x x x x x x x x x 

Scheduled kill 

44 No Abnormalities Detected x x x x x x x x x x x x x x x 

Scheduled kill 

45 No Abnormalities Detected x x x x x x x x x x x x x x x 

Scheduled kill 

46 No Abnormalities Detected x x x x x x x x x x x x x x x 

Scheduled kill 

47 No Abnormalities Detected x x x x x x x x x x x x x x x 

Scheduled kill 

48 No Abnormalities Detected x x x x x x x x x x x x x x x 

Scheduled kill 

X = Present 

Dose Levels: Group 1 - o (Control) Group 2 - 50 mg/kg bw/day Group 3 - 250 mg/kg bw/day Group 4 - 750 mg/kg bw/day 
Harlan Study Number: 41205015 Report Page 157 

Appendix 1 ( continued) Individual Daily Clinical Observations 

Day Numbers Relative to Start Date 

(continued) 

Group Animal 33 33 34 34 34 34 35 35 35 35 36 36 36 36 37 

(Sex) Number Clinical Sign Post 1h Pre Post 1h 5h Pre Post 1h 5h Pre Post 1h 5h Pre 

2(F) 37 No Abnormalities Detected x x x x x x x x x x x x x x x 

Scheduled kill 

38 No Abnormalities Detected x x x x x x x x x x x x x x x 

Scheduled kill 

39 No Abnormalities Detected x x x x x x x x x x x x x x x 

Scheduled kill 

40 No Abnormalities Detected x x x x x x x x x x x x x x x 

Scheduled kill 

41 No Abnormalities Detected x x x x x x x x x x x x x x x 

Scheduled kill 

42 No Abnormalities Detected x x x x x x x x x x x x x x x 

Scheduled kill 

43 No Abnormalities Detected x x x x x x x x x x x x x x x 

Scheduled kill 

44 No Abnormalities Detected x x x x x x x x x x x x x x x 

Scheduled kill 

45 No Abnormalities Detected x x x x x x x x x x x x x x x 

Scheduled kill 

46 No Abnormalities Detected x x x x x x x x x x x x x x x 

Scheduled kill 

47 No Abnormalities Detected x x x x x x x x x x x x x x x 

Scheduled kill 

48 No Abnormalities Detected x x x x x x x x x x x x x x x 

Scheduled kill 

X = Present 

Dose Levels: Group 1 - o (Control) Group 2 - 50 mg/kg bw/day Group 3 - 250 mg/kg bw/day Group 4 - 750 mg/kg bw/day 
Harlan Study Number: 41205015 Report Page 158 

Appendix 1 ( continued) Individual Daily Clinical Observations 

Day Numbers Relative to Start Date 

(continued) 

Group Animal 37 37 37 38 38 38 39 39 39 40 40 40 41 41 41 

(Sex) Number Clinical Sign Post 1h 5h Pre Post 1h Pre Post 1h Pre Post 1 h Pre Post 1h 

2(F) 37 No Abnormalities Detected x x x x x x x x x x x x x x x 

Scheduled kill 

38 No Abnormalities Detected x x x x x x x x x x x x x x x 

Scheduled kill 

39 No Abnormalities Detected x x x x x x x x x x x x x x x 

Scheduled kill 

40 No Abnormalities Detected x x x x x x x x x x x x x x x 

Scheduled kill 

41 No Abnormalities Detected x x x x x x x x x x x x x x x 

Scheduled kill 

42 No Abnormalities Detected x x x x x x x x x x x x x x x 

Scheduled kill 

43 No Abnormalities Detected x x x x x x x x x x x x x x x 

Scheduled kill 

44 No Abnormalities Detected x x x x x x x x x x x x x x x 

Scheduled kill 

45 No Abnormalities Detected x x x x x x x x x x x x x x x 

Scheduled kill 

46 No Abnormalities Detected x x x x x x x x x x x x x x x 

Scheduled kill 

47 No Abnormalities Detected x x x x x x x x x x x x x x x 

Scheduled kill 

48 No Abnormalities Detected x x x x x x x x x x x x x x x 

Scheduled kill 

X = Present 

Dose Levels: Group 1 - O (Control) Group 2 - 50 mg/kg bw/day Group 3 - 250 mg/kg bw/day Group 4 - 750 mg/kg bw/day 
Harlan Study Number: 41205015 Report Page 159 

Appendix 1 ( continued) Individual Daily Clinical Observations 

Day Numbers Relative to Start Date 

(continued) 

Group Animal 42 42 42 42 42 43 43 43 43 43 44 44 44 44 44 

(Sex) Number Clinical Sign A.M. Pre Post 1h 5h A.M. Pre Post 1 h 5h A.M. Pre Post 1h 5h 

2(F) 37 No Abnormalities Detected x x x x x x x x x 

Scheduled kill x 

38 No Abnormalities Detected x x x x x x x x x x x x 

Scheduled kill 

39 No Abnormalities Detected x x x x x 

Scheduled kill x 

40 No Abnormalities Detected x x x x x 

Scheduled kill x 

41 No Abnormalities Detected x 

Scheduled kill x 

42 No Abnormalities Detected x 

Scheduled kill x 

43 No Abnormalities Detected x x x x x x x x x x x x 

Scheduled kill 

44 No Abnormalities Detected x x x x x x x x x x x x 

Scheduled kill 

45 No Abnormalities Detected x x x x x 

Scheduled kill x 

46 No Abnormalities Detected x x x x x 

Scheduled kill x 

47 No Abnormalities Detected x x x x x x x x x 

Scheduled kill x 

48 No Abnormalities Detected x x x x x x x x x 

Scheduled kill x 

X = Present 

Dose Levels: Group 1 - o (Control) Group 2 - 50 mg/kg bw/day Group 3 - 250 mg/kg bw/day Group 4 - 750 mg/kg bw/day 
Harlan Study Number: 41205015 Report 

Appendix 1 ( continued) Individual Daily Clinical Observations 

Day Numbers Relative to Start Date 

(continued) 

Group Animal 

(Sex) Number Clinical Sign 

2(F) 37 No Abnormalities Detected 

Scheduled kill 

38 No Abnormalities Detected 

Scheduled kill 

39 No Abnormalities Detected 

Scheduled kill 

40 No Abnormalities Detected 

Scheduled kill 

41 No Abnormalities Detected 

Scheduled kill 

42 No Abnormalities Detected 

Scheduled kill 

43 No Abnormalities Detected 

Scheduled kill 

44 No Abnormalities Detected 

Scheduled kill 

45 No Abnormalities Detected 

Scheduled kill 

46 No Abnormalities Detected 

Scheduled kill 

47 No Abnormalities Detected 

Scheduled kill 

48 No Abnormalities Detected 

Scheduled kill 

X = Present 

Dose Levels: Group 1 - o (Control) 

45 45 45 45 45 46 46 46 46 47 47 47 48 48 48 

A.M. Pre Post 1h 5h A.M. Pre Post 1h Pre Post 1h Pre Post 1h 

x 

x 

x 

x 

x 

x 

Group 2 - 50 mg/kg bw/day Group 3 - 250 mg/kg bw/day Group 4 - 750 mg/kg bw/day 

Page 160 
Harlan Study Number: 41205015 Report 

Appendix 1 ( continued) Individual Daily Clinical Observations 

Day Numbers Relative to Start Date 

(continued) 

Group Animal 

(Sex) Number Clinical Sign 

2(F) 37 No Abnormalities Detected 

Scheduled kill 

38 No Abnormalities Detected 

Scheduled kill 

39 No Abnormalities Detected 

Scheduled kill 

40 No Abnormalities Detected 

Scheduled kill 

41 No Abnormalities Detected 

Scheduled kill 

42 No Abnormalities Detected 

Scheduled kill 

43 No Abnormalities Detected 

Scheduled kill 

44 No Abnormalities Detected 

Scheduled kill 

45 No Abnormalities Detected 

Scheduled kill 

46 No Abnormalities Detected 

Scheduled kill 

47 No Abnormalities Detected 

Scheduled kill 

48 No Abnormalities Detected 

Scheduled kill 

X = Present 

Dose Levels: Group 1 - O (Control) 

48 49 49 49 49 50 50 50 50 51 51 51 51 52 52 

5h Pre Post 1h 5h Pre Post 1h 5h Pre Post 1h 5h Pre Post 

Group 2 - 50 mg/kg bw/day Group 3 - 250 mg/kg bw/day Group 4 - 750 mg/kg bw/day 

Page 161 
Harlan Study Number: 41205015 Report 

Appendix 1 ( continued) Individual Daily Clinical Observations 

Day Numbers Relative to Start Date 

(continued) 

Group Animal 

(Sex) Number Clinical Sign 

2(F) 37 No Abnormalities Detected 

Scheduled kill 

38 No Abnormalities Detected 

Scheduled kill 

39 No Abnormalities Detected 

Scheduled kill 

40 No Abnormalities Detected 

Scheduled kill 

41 No Abnormalities Detected 

Scheduled kill 

42 No Abnormalities Detected 

Scheduled kill 

43 No Abnormalities Detected 

Scheduled kill 

44 No Abnormalities Detected 

Scheduled kill 

45 No Abnormalities Detected 

Scheduled kill 

46 No Abnormalities Detected 

Scheduled kill 

47 No Abnormalities Detected 

Scheduled kill 

48 No Abnormalities Detected 

Scheduled kill 

X = Present 

52 

1h 

52 

5h 

53 

A.M. 

53 

Pre 

53 

Post 

53 

1h 

Dose Levels: Group 1 - o (Control) Group 2 - 50 mg/kg bw/day Group 3 - 250 mg/kg bw/day 

54 

A.M. 

Group 4 - 750 mg/kg bw/day 

Page 162 
Harlan Study Number: 41205015 Report Page 163 

Appendix 1 ( continued) Individual Daily Clinical Observations 

Day Numbers Relative to Start Date 

Group Animal 1 1 1 1 2 2 2 2 3 3 3 3 4 4 4 

(Sex) Number Clinical Sign Pre Post 1h Sh Pre Post 1h Sh Pre Post 1h Sh Pre Post 1h 

3(F) 61 No Abnormalities Detected x x x x x x x x x x x x x x x 

Scheduled kill 

62 No Abnormalities Detected x x x x x x x x x x x x x x x 

Scheduled kill 

63 No Abnormalities Detected x x x x x x x x x x x x x x x 

Scheduled kill 

64 No Abnormalities Detected x x x x x x x x x x x x x x x 

Scheduled kill 

65 No Abnormalities Detected x x x x x x x x x x x x x x x 

Scheduled kill 

66 No Abnormalities Detected x x x x x x x x x x x x x x x 

Scheduled kill 

67 No Abnormalities Detected x x x x x x x x x x x x x x x 

Scheduled kill 

68 No Abnormalities Detected x x x x x x x x x x x x x x x 

Scheduled kill 

69 No Abnormalities Detected x x x x x x x x x x x x x x x 

Scheduled kill 

70 No Abnormalities Detected x x x x x x x x x x x x x x x 

Scheduled kill 

71 No Abnormalities Detected x x x x x x x x x x x x x x x 

Scheduled kill 

72 No Abnormalities Detected x x x x x x x x x x x x x x x 

Scheduled kill 

X = Present 

Dose Levels: Group 1 - o (Control) Group 2 - 50 mg/kg bw/day Group 3 - 250 mg/kg bw/day Group 4 - 750 mg/kg bw/day 
Harlan Study Number: 41205015 Report Page 164 

Appendix 1 ( continued) Individual Daily Clinical Observations 

Day Numbers Relative to Start Date 

(continued) 

Group Animal 5 5 5 6 6 6 6 7 7 7 7 8 8 8 8 

(Sex) Number Clinical Sign Pre Post 1h Pre Post 1h 5h Pre Post 1h 5h Pre Post 1h 5h 

3(F) 61 No Abnormalities Detected x x x x x x x x x x x x x x x 

Scheduled kill 

62 No Abnormalities Detected x x x x x x x x x x x x x x x 

Scheduled kill 

63 No Abnormalities Detected x x x x x x x x x x x x x x x 

Scheduled kill 

64 No Abnormalities Detected x x x x x x x x x x x x x x x 

Scheduled kill 

65 No Abnormalities Detected x x x x x x x x x x x x x x x 

Scheduled kill 

66 No Abnormalities Detected x x x x x x x x x x x x x x x 

Scheduled kill 

67 No Abnormalities Detected x x x x x x x x x x x x x x x 

Scheduled kill 

68 No Abnormalities Detected x x x x x x x x x x x x x x x 

Scheduled kill 

69 No Abnormalities Detected x x x x x x x x x x x x x x x 

Scheduled kill 

70 No Abnormalities Detected x x x x x x x x x x x x x x x 

Scheduled kill 

71 No Abnormalities Detected x x x x x x x x x x x x x x x 

Scheduled kill 

72 No Abnormalities Detected x x x x x x x x x x x x x x x 

Scheduled kill 

X = Present 

Dose Levels: Group 1 - O (Control) Group 2 - 50 mg/kg bw/day Group 3 - 250 mg/kg bw/day Group 4 - 750 mg/kg bw/day 
Harlan Study Number: 41205015 Report Page 165 

Appendix 1 ( continued) Individual Daily Clinical Observations 

Day Numbers Relative to Start Date 

(continued) 

Group Animal 9 9 9 9 10 10 10 10 11 11 11 12 12 12 13 

(Sex) Number Clinical Sign Pre Post 1h 5h Pre Post 1h 5h Pre Post 1h Pre Post 1h Pre 

3(F) 61 No Abnormalities Detected x x x x x x x x x x x x x x x 

Scheduled kill 

62 No Abnormalities Detected x x x x x x x x x x x x x x x 

Scheduled kill 

63 No Abnormalities Detected x x x x x x x x x x x x x x x 

Scheduled kill 

64 No Abnormalities Detected x x x x x x x x x x x x x x x 

Scheduled kill 

65 No Abnormalities Detected x x x x x x x x x x x x x x x 

Scheduled kill 

66 No Abnormalities Detected x x x x x x x x x x x x x x x 

Scheduled kill 

67 No Abnormalities Detected x x x x x x x x x x x x x x x 

Scheduled kill 

68 No Abnormalities Detected x x x x x x x x x x x x x x x 

Scheduled kill 

69 No Abnormalities Detected x x x x x x x x x x x x x x x 

Scheduled kill 

70 No Abnormalities Detected x x x x x x x x x x x x x x x 

Scheduled kill 

71 No Abnormalities Detected x x x x x x x x x x x x x x x 

Scheduled kill 

72 No Abnormalities Detected x x x x x x x x x x x x x x x 

Scheduled kill 

X = Present 

Dose Levels: Group 1 - O (Control) Group 2 - 50 mg/kg bw/day Group 3 - 250 mg/kg bw/day Group 4 - 750 mg/kg bw/day 
Harlan Study Number: 41205015 Report Page 166 

Appendix 1 ( continued) Individual Daily Clinical Observations 

Day Numbers Relative to Start Date 

(continued) 

Group Animal 13 13 13 14 14 14 14 15 15 15 15 16 16 16 16 

(Sex) Number Clinical Sign Post 1h 5h Pre Post 1h 5h Pre Post 1h 5h Pre Post 1h 5h 

3(F) 61 No Abnormalities Detected x x x x x x x x x x x x x x x 

Scheduled kill 

62 No Abnormalities Detected x x x x x x x x x x x x x x x 

Scheduled kill 

63 No Abnormalities Detected x x x x x x x x x x x x x x x 

Scheduled kill 

64 No Abnormalities Detected x x x x x x x x x x x x x x x 

Scheduled kill 

65 No Abnormalities Detected x x x x x x x x x x x x x x x 

Scheduled kill 

66 No Abnormalities Detected x x x x x x x x x x x x x x x 

Scheduled kill 

67 No Abnormalities Detected x x x x x x x x x x x x x x x 

Scheduled kill 

68 No Abnormalities Detected x x x x x x x x x x x x x x x 

Scheduled kill 

69 No Abnormalities Detected x x x x x x x x x x x x x x x 

Scheduled kill 

70 No Abnormalities Detected x x x x x x x x x x x x x x x 

Scheduled kill 

71 No Abnormalities Detected x x x x x x x x x x x x x x x 

Scheduled kill 

72 No Abnormalities Detected x x x x x x x x x x x x x x x 

Scheduled kill 

X = Present 

Dose Levels: Group 1 - o (Control) Group 2 - 50 mg/kg bw/day Group 3 - 250 mg/kg bw/day Group 4 - 750 mg/kg bw/day 
Harlan Study Number: 41205015 Report Page 167 

Appendix 1 ( continued) Individual Daily Clinical Observations 

Day Numbers Relative to Start Date 

(continued) 

Group Animal 17 17 17 17 18 18 18 19 19 19 20 20 20 20 21 

(Sex) Number Clinical Sign Pre Post 1h 5h Pre Post 1h Pre Post 1h Pre Post 1h 5h Pre 

3(F) 61 No Abnormalities Detected x x x x x x x x x x x x x x x 

Scheduled kill 

62 No Abnormalities Detected x x x x x x x x x x x x x x x 

Scheduled kill 

63 No Abnormalities Detected x x x x x x x x x x x x x x x 

Scheduled kill 

64 No Abnormalities Detected x x x x x x x x x x x x x x x 

Scheduled kill 

65 No Abnormalities Detected x x x x x x x x x x x x x x x 

Scheduled kill 

66 No Abnormalities Detected x x x x x x x x x x x x x x x 

Scheduled kill 

67 No Abnormalities Detected x x x x x x x x x x x x x x x 

Scheduled kill 

68 No Abnormalities Detected x x x x x x x x x x x x x x x 

Scheduled kill 

69 No Abnormalities Detected x x x x x x x x x x x x x x x 

Scheduled kill 

70 No Abnormalities Detected x x x x x x x x x x x x x x x 

Scheduled kill 

71 No Abnormalities Detected x x x x x x x x x x x x x x x 

Scheduled kill 

72 No Abnormalities Detected x x x x x x x x x x x x x x x 

Scheduled kill 

X = Present 

Dose Levels: Group 1 - O (Control) Group 2 - 50 mg/kg bw/day Group 3 - 250 mg/kg bw/day Group 4 - 750 mg/kg bw/day 
Harlan Study Number: 41205015 Report Page 168 

Appendix 1 ( continued) Individual Daily Clinical Observations 

Day Numbers Relative to Start Date 

(continued) 

Group Animal 21 21 21 22 22 22 22 23 23 23 23 24 24 24 24 

(Sex) Number Clinical Sign Post 1h 5h Pre Post 1h 5h Pre Post 1h 5h Pre Post 1h 5h 

3(F) 61 No Abnormalities Detected x x x x x x x x x x x x x x x 

Scheduled kill 

62 No Abnormalities Detected x x x x x x x x x x x x x x x 

Scheduled kill 

63 No Abnormalities Detected x x x x x x x x x x x x x x x 

Scheduled kill 

64 No Abnormalities Detected x x x x x x x x x x x x x x x 

Scheduled kill 

65 No Abnormalities Detected x x x x x x x x x x x x x x x 

Scheduled kill 

66 No Abnormalities Detected x x x x x x x x x x x x x x x 

Scheduled kill 

67 No Abnormalities Detected x x x x x x x x x x x x x x x 

Scheduled kill 

68 No Abnormalities Detected x x x x x x x x x x x x x x x 

Scheduled kill 

69 No Abnormalities Detected x x x x x x x x x x x x x x x 

Scheduled kill 

70 No Abnormalities Detected x x x x x x x x x x x x x x x 

Scheduled kill 

71 No Abnormalities Detected x x x x x x x x x x x x x x x 

Scheduled kill 

72 No Abnormalities Detected x x x x x x x x x x x x x x x 

Scheduled kill 

X = Present 

Dose Levels: Group 1 - O (Control) Group 2 - 50 mg/kg bw/day Group 3 - 250 mg/kg bw/day Group 4 - 750 mg/kg bw/day 
Harlan Study Number: 41205015 Report Page 169 

Appendix 1 ( continued) Individual Daily Clinical Observations 

Day Numbers Relative to Start Date 

(continued) 

Group Animal 25 25 25 26 26 26 27 27 27 27 28 28 28 28 29 

(Sex) Number Clinical Sign Pre Post 1h Pre Post 1h Pre Post 1h 5h Pre Post 1h 5h Pre 

3(F) 61 No Abnormalities Detected x x x x x x x x x x x x x x x 

Scheduled kill 

62 No Abnormalities Detected x x x x x x x x x x x x x x x 

Scheduled kill 

63 No Abnormalities Detected x x x x x x x x x x x x x x x 

Scheduled kill 

64 No Abnormalities Detected x x x x x x x x x x x x x x x 

Scheduled kill 

65 No Abnormalities Detected x x x x x x x x x x x x x x x 

Scheduled kill 

66 No Abnormalities Detected x x x x x x x x x x x x x x x 

Scheduled kill 

67 No Abnormalities Detected x x x x x x x x x x x x x x x 

Scheduled kill 

68 No Abnormalities Detected x x x x x x x x x x x x x x x 

Scheduled kill 

69 No Abnormalities Detected x x x x x x x x x x x x x x x 

Scheduled kill 

70 No Abnormalities Detected x x x x x x x x x x x x x x x 

Scheduled kill 

71 No Abnormalities Detected x x x x x x x x x x x x x x x 

Scheduled kill 

72 No Abnormalities Detected x x x x x x x x x x x x x x x 

Scheduled kill 

X = Present 

Dose Levels: Group 1 - o (Control) Group 2 - 50 mg/kg bw/day Group 3 - 250 mg/kg bw/day Group 4 - 750 mg/kg bw/day 
Harlan Study Number: 41205015 Report Page 170 

Appendix 1 ( continued) Individual Daily Clinical Observations 

Day Numbers Relative to Start Date 

(continued) 

Group Animal 29 29 29 30 30 30 30 31 31 31 31 32 32 32 33 

(Sex) Number Clinical Sign Post 1h 5h Pre Post 1h 5h Pre Post 1h 5h Pre Post 1h Pre 

3(F) 61 No Abnormalities Detected x x x x x x x x x x x x x x x 

Scheduled kill 

62 No Abnormalities Detected x x x x x x x x x x x x x x x 

Scheduled kill 

63 No Abnormalities Detected x x x x x x x x x x x x x x x 

Scheduled kill 

64 No Abnormalities Detected x x x x x x x x x x x x x x x 

Scheduled kill 

65 No Abnormalities Detected x x x x x x x x x x x x x x x 

Scheduled kill 

66 No Abnormalities Detected x x x x x x x x x x x x x x x 

Scheduled kill 

67 No Abnormalities Detected x x x x x x x x x x x x x x x 

Scheduled kill 

68 No Abnormalities Detected x x x x x x x x x x x x x x x 

Scheduled kill 

69 No Abnormalities Detected x x x x x x x x x x x x x x x 

Scheduled kill 

70 No Abnormalities Detected x x x x x x x x x x x x x x x 

Scheduled kill 

71 No Abnormalities Detected x x x x x x x x x x x x x x x 

Scheduled kill 

72 No Abnormalities Detected x x x x x x x x x x x x x x x 

Scheduled kill 

X = Present 

Dose Levels: Group 1 - O (Control) Group 2 - 50 mg/kg bw/day Group 3 - 250 mg/kg bw/day Group 4 - 750 mg/kg bw/day 
Harlan Study Number: 41205015 Report Page 171 

Appendix 1 ( continued) Individual Daily Clinical Observations 

Day Numbers Relative to Start Date 

(continued) 

Group Animal 33 33 34 34 34 34 35 35 35 35 36 36 36 36 37 

(Sex) Number Clinical Sign Post 1h Pre Post 1h 5h Pre Post 1h 5h Pre Post 1h 5h Pre 

3(F) 61 No Abnormalities Detected x x x x x x x x x x x x x x x 

Scheduled kill 

62 No Abnormalities Detected x x x x x x x x x x x x x x x 

Scheduled kill 

63 No Abnormalities Detected x x x x x x x x x x x x x x x 

Scheduled kill 

64 No Abnormalities Detected x x x x x x x x x x x x x x x 

Scheduled kill 

65 No Abnormalities Detected x x x x x x x x x x x x x x x 

Scheduled kill 

66 No Abnormalities Detected x x x x x x x x x x x x x x x 

Scheduled kill 

67 No Abnormalities Detected x x x x x x x x x x x x x x x 

Scheduled kill 

68 No Abnormalities Detected x x x x x x x x x x x x x x x 

Scheduled kill 

69 No Abnormalities Detected x x x x x x x x x x x x x x x 

Scheduled kill 

70 No Abnormalities Detected x x x x x x x x x x x x x x x 

Scheduled kill 

71 No Abnormalities Detected x x x x x x x x x x x x x x x 

Scheduled kill 

72 No Abnormalities Detected x x x x x x x x x x x x x x x 

Scheduled kill 

X = Present 

Dose Levels: Group 1 - O (Control) Group 2 - 50 mg/kg bw/day Group 3 - 250 mg/kg bw/day Group 4 - 750 mg/kg bw/day 
Harlan Study Number: 41205015 Report Page 172 

Appendix 1 ( continued) Individual Daily Clinical Observations 

Day Numbers Relative to Start Date 

(continued) 

Group Animal 37 37 37 38 38 38 39 39 39 40 40 40 41 41 41 

(Sex) Number Clinical Sign Post 1h 5h Pre Post 1h Pre Post 1h Pre Post 1h Pre Post 1h 

3(F) 61 No Abnormalities Detected x x x x x x x x x x x x x x x 

Scheduled kill 

62 No Abnormalities Detected x x x x x x x x x x x x x x x 

Scheduled kill 

63 No Abnormalities Detected x x x x x x x x x x x x x x x 

Scheduled kill 

64 No Abnormalities Detected x x x x x x x x x x x x x x x 

Scheduled kill 

65 No Abnormalities Detected x x x x x x x x x x x x x x x 

Scheduled kill 

66 No Abnormalities Detected x x x x x x x x x x x x x x x 

Scheduled kill 

67 No Abnormalities Detected x x x x x x x x x x x x x x x 

Scheduled kill 

68 No Abnormalities Detected x x x x x x x x x x x x x x x 

Scheduled kill 

69 No Abnormalities Detected x x x x x x x x x x x x x x x 

Scheduled kill 

70 No Abnormalities Detected x x x x x x x x x x x x x x x 

Scheduled kill 

71 No Abnormalities Detected x x x x x x x x x x x x x x x 

Scheduled kill 

72 No Abnormalities Detected x x x x x x x x x x x x x x x 

Scheduled kill 

X = Present 

Dose Levels: Group 1 - o (Control) Group 2 - 50 mg/kg bw/day Group 3 - 250 mg/kg bw/day Group 4 - 750 mg/kg bw/day 
Harlan Study Number: 41205015 Report Page 173 

Appendix 1 ( continued) Individual Daily Clinical Observations 

Day Numbers Relative to Start Date 

(continued) 

Group Animal 42 42 42 42 42 43 43 43 43 43 44 44 44 44 44 

(Sex) Number Clinical Sign A.M. Pre Post 1h Sh A.M. Pre Post 1h Sh A.M. Pre Post 1h Sh 

3(F) 61 No Abnormalities Detected x x x x x x x x x 

Scheduled kill x 

62 No Abnormalities Detected x x x x x x x x x x x x 

Scheduled kill 

63 No Abnormalities Detected x x x x x 

Scheduled kill x 

64 No Abnormalities Detected x x x x x x x x x 

Scheduled kill x 

65 No Abnormalities Detected x x x x x x x x x 

Scheduled kill x 

66 No Abnormalities Detected x 

Scheduled kill x 

67 No Abnormalities Detected x x x x x x x x x x x x 

Scheduled kill 

68 No Abnormalities Detected x 

Scheduled kill x 

69 No Abnormalities Detected x x x x x x x x x 

Scheduled kill x 

70 No Abnormalities Detected x x x x x 

Scheduled kill x 

71 No Abnormalities Detected x x x x x x x x x 

Scheduled kill x 

72 No Abnormalities Detected x x x x x x x x x x x x 

Scheduled kill 

X = Present 

Dose Levels: Group 1 - o (Control) Group 2 - 50 mg/kg bw/day Group 3 - 250 mg/kg bw/day Group 4 - 750 mg/kg bw/day 
Harlan Study Number: 41205015 Report Page 174 

Appendix 1 ( continued) Individual Daily Clinical Observations 

Day Numbers Relative to Start Date 

(continued) 

Group Animal 45 45 45 45 45 46 46 46 46 47 47 47 48 48 48 

(Sex) Number Clinical Sign A.M. Pre Post 1h Sh A.M. Pre Post 1h Pre Post 1h Pre Post 1h 

3(F) 61 No Abnormalities Detected 

Scheduled kill 

62 No Abnormalities Detected x x x x x 

Scheduled kill x 

63 No Abnormalities Detected 

Scheduled kill 

64 No Abnormalities Detected 

Scheduled kill 

65 No Abnormalities Detected 

Scheduled kill 

66 No Abnormalities Detected 

Scheduled kill 

67 No Abnormalities Detected x 

Scheduled kill x 

68 No Abnormalities Detected 

Scheduled kill 

69 No Abnormalities Detected 

Scheduled kill 

70 No Abnormalities Detected 

Scheduled kill 

71 No Abnormalities Detected 

Scheduled kill 

72 No Abnormalities Detected x x x x x 

Scheduled kill x 

X = Present 

Dose Levels: Group 1 - O (Control) Group 2 - 50 mg/kg bw/day Group 3 - 250 mg/kg bw/day Group 4 - 750 mg/kg bw/day 
Harlan Study Number: 41205015 Report 

Appendix 1 ( continued) Individual Daily Clinical Observations 

Day Numbers Relative to Start Date 

(continued) 

Group Animal 

(Sex) Number Clinical Sign 

3(F) 61 No Abnormalities Detected 

Scheduled kill 

62 No Abnormalities Detected 

Scheduled kill 

63 No Abnormalities Detected 

Scheduled kill 

64 No Abnormalities Detected 

Scheduled kill 

65 No Abnormalities Detected 

Scheduled kill 

66 No Abnormalities Detected 

Scheduled kill 

67 No Abnormalities Detected 

Scheduled kill 

68 No Abnormalities Detected 

Scheduled kill 

69 No Abnormalities Detected 

Scheduled kill 

70 No Abnormalities Detected 

Scheduled kill 

71 No Abnormalities Detected 

Scheduled kill 

72 No Abnormalities Detected 

Scheduled kill 

X = Present 

48 49 49 49 49 50 50 50 50 51 51 51 51 

5h Pre Post 1h 5h Pre Post 1h 5h Pre Post 1h 5h 

52 52 

Pre Post 

Dose Levels: Group 1 - o (Control) Group 2 - 50 mg/kg bw/day Group 3 - 250 mg/kg bw/day Group 4 - 750 mg/kg bw/day 

Page 175 
Harlan Study Number: 41205015 Report 

Appendix 1 ( continued) Individual Daily Clinical Observations 

Day Numbers Relative to Start Date 

(continued) 

Group Animal 

(Sex) Number Clinical Sign 

3(F) 61 No Abnormalities Detected 

Scheduled kill 

62 No Abnormalities Detected 

Scheduled kill 

63 No Abnormalities Detected 

Scheduled kill 

64 No Abnormalities Detected 

Scheduled kill 

65 No Abnormalities Detected 

Scheduled kill 

66 No Abnormalities Detected 

Scheduled kill 

67 No Abnormalities Detected 

Scheduled kill 

68 No Abnormalities Detected 

Scheduled kill 

69 No Abnormalities Detected 

Scheduled kill 

70 No Abnormalities Detected 

Scheduled kill 

71 No Abnormalities Detected 

Scheduled kill 

72 No Abnormalities Detected 

Scheduled kill 

X = Present 

52 

1h 

52 

5h 

53 

A.M. 

53 

Pre 

53 

Post 

53 

1h 

Dose Levels: Group 1 - o (Control) Group 2 - 50 mg/kg bw/day Group 3 - 250 mg/kg bw/day 

54 

A.M. 

Group 4 - 750 mg/kg bw/day 

Page 176 
Harlan Study Number: 41205015 Report Page 177 

Appendix 1 ( continued) Individual Daily Clinical Observations 

Day Numbers Relative to Start Date 

Group Animal 1 1 1 1 2 2 2 2 3 3 3 3 4 4 4 

(Sex) Number Clinical Sign Pre Post 1h 5h Pre Post 1h 5h Pre Post 1h 5h Pre Post 1h 

4(F) 85 No Abnormalities Detected x x x x x x x x x x x x x x x 

Scheduled kill 

Increased salivation 

86 No Abnormalities Detected x x x x x x x x x x x x x x x 

Scheduled kill 

Increased salivation 

87 No Abnormalities Detected x x x x x x x x x x x x x x x 

Scheduled kill 

88 No Abnormalities Detected x x x x x x x x x x x x x x x 

Scheduled kill 

89 No Abnormalities Detected x x x x x x x x x x x x x x x 

Scheduled kill 

Increased salivation 

90 No Abnormalities Detected x x x x x x x x x x x x x x x 

Scheduled kill 

Increased salivation 

91 No Abnormalities Detected x x x x x x x x x x x x x x x 

Scheduled kill 

Increased salivation 

92 No Abnormalities Detected x x x x x x x x x x x x x x x 

Scheduled kill 

Increased salivation 

93 No Abnormalities Detected x x x x x x x x x x x x x x x 

Scheduled kill 

Increased salivation 

94 No Abnormalities Detected x x x x x x x x x x x x x x x 

Scheduled kill 

Increased salivation 

X = Present 

Dose Levels: Group 1 - o (Control) Group 2 - 50 mg/kg bw/day Group 3 - 250 mg/kg bw/day Group 4 - 750 mg/kg bw/day 
Harlan Study Number: 41205015 Report Page 178 

Appendix 1 ( continued) Individual Daily Clinical Observations 

Day Numbers Relative to Start Date 

(continued) 

Group Animal 5 5 5 6 6 6 6 7 7 7 7 8 8 8 8 

(Sex) Number Clinical Sign Pre Post 1h Pre Post 1h 5h Pre Post 1h 5h Pre Post 1h 5h 

4(F) 85 No Abnormalities Detected x x x x x x x x x x x x x x x 

Scheduled kill 

Increased salivation 

86 No Abnormalities Detected x x x x x x x x x x x x x x x 

Scheduled kill 

Increased salivation 

87 No Abnormalities Detected x x x x x x x x x x x x x x x 

Scheduled kill 

88 No Abnormalities Detected x x x x x x x x x x x x x x x 

Scheduled kill 

89 No Abnormalities Detected x x x x x x x x x x x x x x x 

Scheduled kill 

Increased salivation .. 90 No Abnormalities Detected x x x x x x x x x x x x x x x 

Scheduled kill 

Increased salivation 

91 No Abnormalities Detected x x x x x x x x x x x x x x x 

Scheduled kill 

Increased salivation 

92 No Abnormalities Detected x x x x x x x x x x x x x x x 

Scheduled kill 

Increased salivation 

93 No Abnormalities Detected x x x x x x x x x x x x x x x 

Scheduled kill 

Increased salivation 

94 No Abnormalities Detected x x x x x x x x x x x x x x x 

Scheduled kill 

Increased salivation 

X = Present 

Dose Levels: Group 1 - O (Control) Group 2 - 50 mg/kg bw/day Group 3 - 250 mg/kg bw/day Group 4 - 750 mg/kg bw/day 
Harlan Study Number: 41205015 Report Page 179 

Appendix 1 ( continued) Individual Daily Clinical Observations 

Day Numbers Relative to Start Date 

(continued) 

Group Animal 9 9 9 9 10 10 10 10 11 11 11 12 12 12 13 

(Sex) Number Clinical Sign Pre Post 1h Sh Pre Post 1h Sh Pre Post 1h Pre Post 1h Pre 

4(F) 85 No Abnormalities Detected x x x x x x x x x x x x x x x 

Scheduled kill 

Increased salivation 

86 No Abnormalities Detected x x x x x x x x x x x x x x x 

Scheduled kill 

Increased salivation 

87 No Abnormalities Detected x x x x x x x x x x x x x x x 

Scheduled kill 

88 No Abnormalities Detected x x x x x x x x x x x x x x x 

Scheduled kill 

89 No Abnormalities Detected x x x x x x x x x x x x x x x 

Scheduled kill 

Increased salivation 

90 No Abnormalities Detected x x x x x x x x x x x x x x x 

Scheduled kill 

Increased salivation 

91 No Abnormalities Detected x x x x x x x x x x x x x x x 

Scheduled kill 

Increased salivation 

92 No Abnormalities Detected x x x x x x x x x x x x x x x 

Scheduled kill 

Increased salivation 

93 No Abnormalities Detected x x x x x x x x x x x x x x x 

Scheduled kill 

Increased salivation 

94 No Abnormalities Detected x x x x x x x x x x x x x x x 

Scheduled kill 

Increased salivation 

X = Present 

Dose Levels: Group 1 - o (Control) Group 2 - 50 mg/kg bw/day Group 3 - 250 mg/kg bw/day Group 4 - 750 mg/kg bw/day 
Harlan Study Number: 41205015 Report Page 180 

Appendix 1 ( continued) Individual Daily Clinical Observations 

Day Numbers Relative to Start Date 

(continued) 

Group Animal 13 13 13 14 14 14 14 15 15 15 15 16 16 16 16 

(Sex) Number Clinical Sign Post 1h Sh Pre Post 1h Sh Pre Post 1h Sh Pre Post 1h Sh 

4(F) 85 No Abnormalities Detected x x x x x x x x x x x x x x x 

Scheduled kill 

Increased salivation 

86 No Abnormalities Detected x x x x x x x x x x x x x x x 

Scheduled kill 

Increased salivation 

87 No Abnormalities Detected x x x x x x x x x x x x x x x 

Scheduled kill 

88 No Abnormalities Detected x x x x x x x x x x x x x x x 

Scheduled kill 

89 No Abnormalities Detected x x x x x x x x x x x x x x x 

Scheduled kill 

Increased salivation 

90 No Abnormalities Detected x x x x x x x x x x x x x x x 

Scheduled kill 

Increased salivation 

91 No Abnormalities Detected x x x x x x x x x x x x x x x 

Scheduled kill 

Increased salivation 

92 No Abnormalities Detected x x x x x x x x x x x x x x x 

Scheduled kill 

Increased salivation 

93 No Abnormalities Detected x x x x x x x x x x x x x x x 

Scheduled kill 

Increased salivation 

94 No Abnormalities Detected x x x x x x x x x x x x x x x 

Scheduled kill 

Increased salivation 

X = Present 

Dose Levels: Group 1 - O (Control) Group 2 - 50 mg/kg bw/day Group 3 - 250 mg/kg bw/day Group 4 - 750 mg/kg bw/day 
Harlan Study Number: 41205015 Report Page 181 

Appendix 1 ( continued) Individual Daily Clinical Observations 

Day Numbers Relative to Start Date 

(continued} 

Group Animal 17 17 17 17 18 18 18 19 19 19 20 20 20 20 21 

(Sex} Number Clinical Sign Pre Post 1h 5h Pre Post 1h Pre Post 1h Pre Post 1h 5h Pre 

4(F} 85 No Abnormalities Detected x x x x x x x x x x x x x x x 

Scheduled kill 

Increased salivation 

86 No Abnormalities Detected x x x x x x x x x x x x x x x 

Scheduled kill 

Increased salivation 

87 No Abnormalities Detected x x x x x x x x x x x x x x x 

Scheduled kill 

88 No Abnormalities Detected x x x x x x x x x x x x x x x 

Scheduled kill 

89 No Abnormalities Detected x x x x x x x x x x x x x x x 

Scheduled kill 

Increased salivation 

90 No Abnormalities Detected x x x x x x x x x x x x x x x 

Scheduled kill 

Increased salivation 

91 No Abnormalities Detected x x x x x x x x x x x x x x x 

Scheduled kill 

Increased salivation 

92 No Abnormalities Detected x x x x x x x x x x x x x x x 

Scheduled kill 

Increased salivation 

93 No Abnormalities Detected x x x x x x x x x x x x x x x 

Scheduled kill 

Increased salivation 

94 No Abnormalities Detected x x x x x x x x x x x x x x x 

Scheduled kill 

Increased salivation 

X = Present 

Dose Levels: Group 1 - O (Control} Group 2 - 50 mg/kg bw/day Group 3 - 250 mg/kg bw/day Group 4 - 750 mg/kg bw/day 
Harlan Study Number: 41205015 Report Page 182 

Appendix 1 ( continued) Individual Daily Clinical Observations 

Day Numbers Relative to Start Date 

(continued) 

Group Animal 21 21 21 22 22 22 22 23 23 23 23 24 24 24 24 

(Sex) Number Clinical Sign Post 1h 5h Pre Post 1h 5h Pre Post 1h 5h Pre Post 1h 5h 

4(F) 85 No Abnormalities Detected x x x x x x x x x x x x x x 

Scheduled kill 

Increased salivation x 

86 No Abnormalities Detected x x x x x x x x x x x x x x x 

Scheduled kill 

Increased salivation 

87 No Abnormalities Detected x x x x x x x x x x x x x x x 

Scheduled kill 

88 No Abnormalities Detected x x x x x x x x x x x x x x x 

Scheduled kill 

89 No Abnormalities Detected x x x x x x x x x x x x x x 

Scheduled kill 

Increased salivation x 

90 No Abnormalities Detected x x x x x x x x x x x x x x x 

Scheduled kill 

Increased salivation 

91 No Abnormalities Detected x x x x x x x x x x x x x x x 

Scheduled kill 

Increased salivation 

92 No Abnormalities Detected x x x x x x x x x x x x x 

Scheduled kill 

Increased salivation x x 

93 No Abnormalities Detected x x x x x x x x x x x x x x x 

Scheduled kill 

Increased salivation 

94 No Abnormalities Detected x x x x x x x x x x x x x 

Scheduled kill 

Increased salivation x x 

X = Present 

Dose Levels: Group 1 - o (Control) Group 2 - 50 mg/kg bw/day Group 3 - 250 mg/kg bw/day Group 4 - 750 mg/kg bw/day 
Harlan Study Number: 41205015 Report Page 183 

Appendix 1 ( continued) Individual Daily Clinical Observations 

Day Numbers Relative to Start Date 

(continued) 

Group Animal 25 25 25 26 26 26 27 27 27 27 28 28 28 28 29 

(Sex) Number Clinical Sign Pre Post 1h Pre Post 1h Pre Post 1h Sh Pre Post 1h Sh Pre 

4(F) 85 No Abnormalities Detected x x x x x x x x x x x x x x 

Scheduled kill 

Increased salivation x 

86 No Abnormalities Detected x x x x x x x x x x x x x 

Scheduled kill 

Increased salivation x x 

87 No Abnormalities Detected x x x x x x x x x x x x x x x 

Scheduled kill 

88 No Abnormalities Detected x x x x x x x x x x x x x x x 

Scheduled kill 

89 No Abnormalities Detected x x x x x x x x x x x x x x x 

Scheduled kill 

Increased salivation 

90 No Abnormalities Detected x x x x x x x x x x x x x 

Scheduled kill 

Increased salivation x x 

91 No Abnormalities Detected x x x x x x x x x x x x 

Scheduled kill 

Increased salivation x x x 

92 No Abnormalities Detected x x x x x x x x x x x x x x x 

Scheduled kill 

Increased salivation 

93 No Abnormalities Detected x x x x x x x x x x x x x x 

Scheduled kill 

Increased salivation x 

94 No Abnormalities Detected x x x x x x x x x x i< x x x x 

Scheduled kill 

Increased salivation 

X = Present 

Dose Levels: Group 1 - O (Control) Group 2 - 50 mg/kg bw/day Group 3 - 250 mg/kg bw/day Group 4 - 750 mg/kg bw/day 
Harlan Study Number: 41205015 Report Page 184 

Appendix 1 ( continued) Individual Daily Clinical Observations 

Day Numbers Relative to Start Date 

(continued) 

Group Animal 29 29 29 30 30 30 30 31 31 31 31 32 32 32 33 

(Sex) Number Clinical Sign Post 1h 5h Pre Post 1h 5h Pre Post 1h 5h Pre Post 1h Pre 

4(F) 85 No Abnormalities Detected x x x x x x x x x x x x x x x 

Scheduled kill 

Increased salivation 

86 No Abnormalities Detected x x x x x x x x x x x x x x x 

Scheduled kill 

Increased salivation 

87 No Abnormalities Detected x x x x x x x x x x x x x x x 

Scheduled kill 

88 No Abnormalities Detected x x x x x x x x x x x x x x x 

Scheduled kill 

89 No Abnormalities Detected x x x x x x x x x x x x x x x 

Scheduled kill 

Increased salivation 

90 No Abnormalities Detected x x x x x x x x x x x x x x x 

Scheduled kill 

Increased salivation 

91 No Abnormalities Detected x x x x x x x x x x x x x x x 

Scheduled kill 

Increased salivation 

92 No Abnormalities Detected x x x x x x x x x x x x x x x 

Scheduled kill 

Increased salivation 

93 No Abnormalities Detected x x x x x x x x x x x x x x x 

Scheduled kill 

Increased salivation 

94 No Abnormalities Detected x x x x x x x x x x x x x x x 

Scheduled kill 

Increased salivation 

X = Present 

Dose Levels: Group 1 - O (Control) Group 2 - 50 mg/kg bw/day Group 3 - 250 mg/kg bw/day Group 4 - 750 mg/kg bw/day 
Harlan Study Number: 41205015 Report Page 185 

Appendix 1 ( continued) Individual Daily Clinical Observations 

Day Numbers Relative to Start Date 

(continued) 

Group Animal 33 33 34 34 34 34 35 35 35 35 36 36 36 36 37 

(Sex) Number Clinical Sign Post 1h Pre Post 1h 5h Pre Post 1h 5h Pre Post 1h 5h Pre 

4(F) 85 No Abnormalities Detected x x x x x x x x x x x x x x x 

Scheduled kill 

Increased salivation 

86 No Abnormalities Detected x x x x x x x x x x x x x x x 

Scheduled kill 

Increased salivation 

87 No Abnormalities Detected x x x x x x x x x x x x x x x 

Scheduled kill 

88 No Abnormalities Detected x x x x x x x x x x x x x x x 

Scheduled kill 

89 No Abnormalities Detected x x x x x x x x x x x x x x x 

Scheduled kill 

Increased salivation 

90 No Abnormalities Detected x x x x x x x x x x x x x x x 

Scheduled kill 

Increased salivation 

91 No Abnormalities Detected x x x x x x x x x x x x x x x 

Scheduled kill 

Increased salivation 

92 No Abnormalities Detected x x x x x x x x x x x x x x x 

Scheduled kill 

Increased salivation 

93 No Abnormalities Detected x x x x x x x x x x x x x x x 

Scheduled kill 

Increased salivation 

94 No Abnormalities Detected x x x x x x x x x x x x x x x 

Scheduled kill 

Increased salivation 

X = Present 

Dose Levels: Group 1 - O (Control) Group 2 - 50 mg/kg bw/day Group 3 - 250 mg/kg bw/day Group 4 - 750 mg/kg bw/day 
Harlan Study Number: 41205015 Report Page 186 

Appendix 1 ( continued) Individual Daily Clinical Observations 

Day Numbers Relative to Start Date 

(continued) 

Group Animal 37 37 37 38 38 38 39 39 39 40 40 40 41 41 41 

(Sex) Number Clinical Sign Post 1h 5h Pre Post 1h Pre Post 1h Pre Post 1h Pre Post 1h 

4(F) 85 No Abnormalities Detected x x x x x x x x x x x x x x x 

Scheduled kill 

Increased salivation 

86 No Abnormalities Detected x x x x x x x x x x x x x x x 

Scheduled kill 

Increased salivation 

87 No Abnormalities Detected x x x x x x x x x x x x x x x 

Scheduled kill 

88 No Abnormalities Detected x x x x x x x x x x x x x x x 

Scheduled kill 

89 No Abnormalities Detected x x x x x x x x x x x x x x x 

Scheduled kill 

Increased salivation 

90 No Abnormalities Detected x x x x x x x x x x x x x x x 

Scheduled kill 

Increased salivation 

91 No Abnormalities Detected x x x x x x x x x x x x x x x 

Scheduled kill 

Increased salivation 

92 No Abnormalities Detected x x x x x x x x x x x x x x x 

Scheduled kill 

Increased salivation 

93 No Abnormalities Detected x x x x x x x x x x x x x x x 

Scheduled kill 

Increased salivation 

94 No Abnormalities Detected x x x x x x x x x x x x x x x 

Scheduled kill 

Increased salivation 

X = Present 

Dose Levels: Group 1 - O (Control) Group 2 - 50 mg/kg bw/day Group 3 - 250 mg/kg bw/day Group 4 - 750 mg/kg bw/day 
Harlan Study Number: 41205015 Report Page 187 

Appendix 1 ( continued) Individual Daily Clinical Observations 

Day Numbers Relative to Start Date 

(continued) 

Group Animal 42 42 42 42 42 43 43 43 43 43 44 44 44 44 44 

(Sex) Number Clinical Sign A.M. Pre Post 1h 5h A.M. Pre Post 1h 5h A.M. Pre Post 1h 5h 

4(F) 85 No Abnormalities Detected x 

Scheduled kill x 

Increased salivation 

86 No Abnormalities Detected x x x x x x x x x 

Scheduled kill x 

Increased salivation 

87 No Abnormalities Detected x 

Scheduled kill x 

88 No Abnormalities Detected x 

Scheduled kill x 

89 No Abnormalities Detected x x x x x 

Scheduled kill x 

Increased salivation 

90 No Abnormalities Detected x x x x x x x x x x x x 

Scheduled kill 

Increased salivation 

91 No Abnormalities Detected x x x x x x x x x 

Scheduled kill x 

Increased salivation 

92 No Abnormalities Detected x 

Scheduled kill x 

Increased salivation 

93 No Abnormalities Detected x x x x x x x x x x x x 

Scheduled kill 

Increased salivation 

94 No Abnormalities Detected x 

Scheduled kill x 

Increased salivation 

X = Present 

Dose Levels: Group 1 - O (Control) Group 2 - 50 mg/kg bw/day Group 3 - 250 mg/kg bw/day Group 4 - 750 mg/kg bw/day 
Harlan Study Number: 41205015 Report Page 188 

Appendix 1 ( continued) Individual Daily Clinical Observations 

Day Numbers Relative to Start Date 

(continued) 

Group Animal 45 45 45 45 45 46 46 46 46 47 47 47 48 48 48 

(Sex) Number Clinical Sign A.M. Pre Post 1h 5h A.M. Pre Post 1 h Pre Post 1h Pre Post 1h 

4(F) 85 No Abnormalities Detected 

Scheduled kill 

Increased salivation 

86 No Abnormalities Detected 

Scheduled kill 

Increased salivation 

87 No Abnormalities Detected 

Scheduled kill 

88 No Abnormalities Detected 

Scheduled kill 

89 No Abnormalities Detected 

Scheduled kill 

Increased salivation 

90 No Abnormalities Detected x x x x x x x x x x x x x 

Scheduled kill 

Increased salivation 

91 No Abnormalities Detected 

Scheduled kill 

Increased salivation 

92 No Abnormalities Detected 

Scheduled kill 

Increased salivation 

93 No Abnormalities Detected x x x x x x x x x x x x x 

Scheduled kill 

Increased salivation 

94 No Abnormalities Detected 

Scheduled kill 

Increased salivation 

X = Present 

Dose Levels: Group 1 - o (Control) Group 2 - 50 mg/kg bw/day Group 3 - 250 mg/kg bw/day Group 4 - 750 mg/kg bw/day 
Harlan Study Number: 41205015 Report Page 189 

Appendix 1 ( continued) Individual Daily Clinical Observations 

Day Numbers Relative to Start Date 

(continued) 

Group Animal 48 49 49 49 49 50 50 50 50 51 51 51 51 52 52 

(Sex) Number Clinical Sign 5h Pre Post 1h 5h Pre Post 1h 5h Pre Post 1h 5h Pre Post 

4(F) 85 No Abnormalities Detected 

Scheduled kill 

Increased salivation 

86 No Abnormalities Detected 

Scheduled kill 

Increased salivation 

87 No Abnormalities Detected 

Scheduled kill 

88 No Abnormalities Detected 

Scheduled kill 

89 No Abnormalities Detected 

Scheduled kill 

Increased salivation 

90 No Abnormalities Detected x x x x x x x x x x x x x x x 

Scheduled kill 

Increased salivation 

91 No Abnormalities Detected 

Scheduled kill 

Increased salivation 

92 No Abnormalities Detected 

Scheduled kill 

Increased salivation 

93 No Abnormalities Detected x x x x x x x x x x x x x x x 

Scheduled kill 

Increased salivation 

94 No Abnormalities Detected 

Scheduled kill 

Increased salivation 

X = Present 

Dose Levels: Group 1 - o (Control) Group 2 - 50 mg/kg bw/day Group 3 - 250 mg/kg bw/day Group 4 - 750 mg/kg bw/day 
Harlan Study Number: 41205015 Report Page 190 

Appendix 1 ( continued) Individual Daily Clinical Observations 

Day Numbers Relative to Start Date 

(continued) 

Group Animal 52 52 53 53 53 53 54 

(Sex) Number Clinical Sign 1h 5h A.M. Pre Post 1h A.M. 

4(F) 85 No Abnormalities Detected 

Scheduled kill 

Increased salivation 

86 No Abnormalities Detected 

Scheduled kill 

Increased salivation 

87 No Abnormalities Detected 

Scheduled kill 

88 No Abnormalities Detected 

Scheduled kill 

89 No Abnormalities Detected 

Scheduled kill 

Increased salivation 

90 No Abnormalities Detected x x x x x x 

Scheduled kill x 

Increased salivation 

91 No Abnormalities Detected 

Scheduled kill 

Increased salivation 

92 No Abnormalities Detected 

Scheduled kill 

Increased salivation 

93 No Abnormalities Detected x x x 

Scheduled kill x 

Increased salivation 

94 No Abnormalities Detected 

Scheduled kill 

Increased salivation 

X = Present 

Dose Levels: Group 1 - O (Control) Group 2 - 50 mg/kg bw/day Group 3 - 250 mg/kg bw/day Group 4 - 750 mg/kg bw/day 
Harlan Study Number: 41205015 Report Page 191 

Appendix 1 ( continued) Individual Daily Clinical Observations 

Day Numbers Relative to Start Date 

Group Animal 1 1 1 1 2 2 2 2 3 3 3 3 4 4 4 

(Sex) Number Clinical Sign Pre Post 1h 5h Pre Post 1h 5h Pre Post 1h 5h Pre Post 1h 

4(F) 95 No Abnormalities Detected x x x x x x x x x x x x x x x 

Scheduled kill 

Increased salivation 

96 No Abnormalities Detected x x x x x x x x x x x x x x x 

Scheduled kill 

Increased salivation 

X = Present 

Dose Levels: Group 1 - O (Control) Group 2 - 50 mg/kg bw/day Group 3 - 250 mg/kg bw/day Group 4 - 750 mg/kg bw/day 
Harlan Study Number: 41205015 Report Page 192 

Appendix 1 ( continued) Individual Daily Clinical Observations 

Day Numbers Relative to Start Date 

(continued) 

Group Animal 5 5 5 6 6 6 6 7 7 7 7 8 8 8 8 

(Sex) Number Clinical Sign Pre Post 1h Pre Post 1h Sh Pre Post 1h Sh Pre Post 1h Sh 

4(F) 95 No Abnormalities Detected x x x x x x x x x x x x x x x 

Scheduled kill 

Increased salivation 

96 No Abnormalities Detected x x x x x x x x x x x x x x x 

Scheduled kill 

Increased salivation 

X = Present 

Dose Levels: Group 1 - o (Control) Group 2 - 50 mg/kg bw/day Group 3 - 250 mg/kg bw/day Group 4 - 750 mg/kg bw/day 
Harlan Study Number: 41205015 Report Page 193 

Appendix 1 ( continued) Individual Daily Clinical Observations 

Day Numbers Relative to Start Date 

(continued) 

Group Animal 9 9 9 9 10 10 10 10 11 11 11 12 12 12 13 

(Sex) Number Clinical Sign Pre Post 1h 5h Pre Post 1h 5h Pre Post 1h Pre Post 1h Pre 

4(F) 95 No Abnormalities Detected x x x x x x x x x x x x x x x 

Scheduled kill 

Increased salivation 

96 No Abnormalities Detected x x x x x x x x x x x x x x x 

Scheduled kill 

Increased salivation 

X = Present 

Dose Levels: Group 1 - o (Control) Group 2 - 50 mg/kg bw/day Group 3 - 250 mg/kg bw/day Group 4 - 750 mg/kg bw/day 
Harlan Study Number: 41205015 Report Page 194 

Appendix 1 ( continued) Individual Daily Clinical Observations 

Day Numbers Relative to Start Date 

(continued) 

Group Animal 13 13 13 14 14 14 14 15 15 15 15 16 16 16 16 

(Sex) Number Clinical Sign Post 1h 5h Pre Post 1h 5h Pre Post 1h 5h Pre Post 1h 5h 

4(F) 95 No Abnormalities Detected x x x x x x x x x x x x x x x 

Scheduled kill 

Increased salivation 

96 No Abnormalities Detected x x x x x x x x x x x x x x x 

Scheduled kill 

Increased salivation 

X = Present 

Dose Levels: Group 1 - o (Control) Group 2 - 50 mg/kg bw/day Group 3 - 250 mg/kg bw/day Group 4 - 750 mg/kg bw/day 
Harlan Study Number: 41205015 Report Page 195 

Appendix 1 ( continued) Individual Daily Clinical Observations 

Day Numbers Relative to Start Date 

(continued) 

Group Animal 17 17 17 17 18 18 18 19 19 19 20 20 20 20 21 

(Sex) Number Clinical Sign Pre Post 1h 5h Pre Post 1h Pre Post 1h Pre Post 1h 5h Pre 

4(F) 95 No Abnormalities Detected x x x x x x x x x x x x x x x 

Scheduled kill 

Increased salivation 

96 No Abnormalities Detected x x x x x x x x x x x x x x x 

Scheduled kill 

Increased salivation 

X = Present 

Dose Levels: Group 1 - o (Control) Group 2 - 50 mg/kg bw/day Group 3 - 250 mg/kg bw/day Group 4 - 750 mg/kg bw/day 
Harlan Study Number: 41205015 Report Page 196 

Appendix 1 ( continued) Individual Daily Clinical Observations 

Day Numbers Relative to Start Date 

(continued) 

Group Animal 21 21 21 22 22 22 22 23 23 23 23 24 24 24 24 

(Sex) Number Clinical Sign Post 1h 5h Pre Post 1h 5h Pre Post 1h 5h Pre Post 1h 5h 

4(F) 95 No Abnormalities Detected x x x x x x x x x x x x x x x 

Scheduled kill 

Increased salivation 

96 No Abnormalities Detected x x x x x x x x x x x x x 

Scheduled kill 

Increased salivation x x 

X = Present 

Dose Levels: Group 1 - O (Control) Group 2 - 50 mg/kg bw/day Group 3 - 250 mg/kg bw/day Group 4 - 750 mg/kg bw/day 
Harlan Study Number: 41205015 Report Page 197 

Appendix 1 ( continued) Individual Daily Clinical Observations 

Day Numbers Relative to Start Date 

(continued) 

Group Animal 25 25 25 26 26 26 27 27 27 27 28 28 28 28 29 

(Sex) Number Clinical Sign Pre Post 1h Pre Post 1h Pre Post 1h 5h Pre Post 1h 5h Pre 

4(F) 95 No Abnormalities Detected x x x x x x x x x x x x x 

Scheduled kill 

Increased salivation x x 

96 No Abnormalities Detected x x x x x x x x x x x x x x x 

Scheduled kill 

Increased salivation 

X = Present 

Dose Levels: Group 1 - O (Control) Group 2 - 50 mg/kg bw/day Group 3 - 250 mg/kg bw/day Group 4 - 750 mg/kg bw/day 
Harlan Study Number: 41205015 Report Page 198 

Appendix 1 ( continued) Individual Daily Clinical Observations 

Day Numbers Relative to Start Date 

(continued) 

Group Animal 29 29 29 30 30 30 30 31 31 31 31 32 32 32 33 

(Sex) Number Clinical Sign Post 1h Sh Pre Post 1h Sh Pre Post 1h Sh Pre Post 1h Pre 

4(F) 95 No Abnormalities Detected x x x x x x x x x x x x x x x 

Scheduled kill 

Increased salivation 

96 No Abnormalities Detected x x x x x x x x x x x x x x x 

Scheduled kill 

Increased salivation 

X = Present 

Dose Levels: Group 1 - O (Control) Group 2 - 50 mg/kg bw/day Group 3 - 250 mg/kg bw/day Group 4 - 750 mg/kg bw/day 
Harlan Study Number: 41205015 Report Page 199 

Appendix 1 ( continued) Individual Daily Clinical Observations 

Day Numbers Relative to Start Date 

(continued) 

Group Animal 33 33 34 34 34 34 35 35 35 35 36 36 36 36 37 

(Sex) Number Clinical Sign Post 1h Pre Post 1h 5h Pre Post 1h 5h Pre Post 1 h 5h Pre 

4(F) 95 No Abnormalities Detected x x x x x x x x x x x x x x x 

Scheduled kill 

Increased salivation 

96 No Abnormalities Detected x x x x x x x x x x x x x x x 

Scheduled kill 

Increased salivation 

X = Present 

Dose Levels: Group 1 - o (Control) Group 2 - 50 mg/kg bw/day Group 3 - 250 mg/kg bw/day Group 4 - 750 mg/kg bw/day 
Harlan Study Number: 41205015 Report Page 200 

Appendix 1 ( continued) Individual Daily Clinical Observations 

Day Numbers Relative to Start Date 

(continued) 

Group Animal 37 37 37 38 38 38 39 39 39 40 40 40 41 41 41 

(Sex) Number Clinical Sign Post 1h 5h Pre Post 1h Pre Post 1h Pre Post 1h Pre Post 1h 

4(F) 95 No Abnormalities Detected x x x x x x x x x x x x x x x 

Scheduled kill 

Increased salivation 

96 No Abnormalities Detected x x x x x x x x x x x x x x x 

Scheduled kill 

Increased salivation 

X = Present 

Dose Levels: Group 1 - o (Control) Group 2 - 50 mg/kg bw/day Group 3 - 250 mg/kg bw/day Group 4 - 750 mg/kg bw/day 
Harlan Study Number: 41205015 

Appendix 1 ( continued) 

Report 

Individual Daily Clinical Observations 

Day Numbers Relative to Start Date 

(continued) 

Group Animal 42 42 42 42 42 43 43 43 43 43 44 44 44 44 44 

(Sex) Number Clinical Sign 

4(F) 95 No Abnormalities Detected 

Scheduled kill 

Increased salivation 

96 No Abnormalities Detected 

Scheduled kill 

Increased salivation 

X = Present 

Dose Levels: Group 1 - O (Control) 

A.M. Pre Post 1h 5h A.M. Pre Post 1h 5h A.M. Pre Post 1h 5h 

x x x 

x x x 

Group 2 - 50 mg/kg bw/day 

x 

x x 

x 

x x 

Group 3 - 250 mg/kg bw/day 

x x x x x 

Group 4 - 750 mg/kg bw/day 

x 

Page 201 
Harlan Study Number: 41205015 Report 

Appendix 1 ( continued) Individual Daily Clinical Observations 

Day Numbers Relative to Start Date 

(continued) 

Group Animal 

(Sex) Number Clinical Sign 

4(F) 95 No Abnormalities Detected 

Scheduled kill 

Increased salivation 

96 No Abnormalities Detected 

Scheduled kill 

Increased salivation 

X = Present 

Dose Levels: Group 1 - O (Control) 

45 45 45 45 45 46 46 46 46 47 47 47 48 48 48 

A.M. Pre Post 1h 5h A.M. Pre Post 1h Pre Post 1h Pre Post 1h 

x 

x 

Group 2 - 50 mg/kg bw/day Group 3 - 250 mg/kg bw/day Group 4 - 750 mg/kg bw/day 

Page202 
Harlan Study Number: 41205015 Report 

Appendix 1 ( continued) Individual Daily Clinical Observations 

Day Numbers Relative to Start Date 

(continued) 

Group Animal 

(Sex) Number Clinical Sign 

4(F) 95 No Abnormalities Detected 

Scheduled kill 

Increased salivation 

96 No Abnormalities Detected 

Scheduled kill 

Increased salivation 

X = Present 

48 49 49 49 49 50 50 50 50 51 51 51 51 

5h Pre Post 1h 5h Pre Post 1h 5h Pre Post 1h 5h 

52 52 

Pre Post 

Dose Levels: Group 1 - o (Control) Group 2 - 50 mg/kg bw/day Group 3 - 250 mg/kg bw/day Group 4 - 750 mg/kg bw/day 

Page 203 
Harlan Study Number: 41205015 Report 

Appendix 1 ( continued) Individual Daily Clinical Observations 

Day Numbers Relative to Start Date 

(continued) 

Group Animal 

(Sex) Number Clinical Sign 

4(F) 95 No Abnormalities Detected 

Scheduled kill 

Increased salivation 

96 No Abnormalities Detected 

Scheduled kill 

Increased salivation 

X = Present 

52 

1h 

52 

5h 

53 

A.M. 

53 

Pre 

53 

Post 

53 

1h 

Dose Levels: Group 1 - o (Control) Group 2 - 50 mg/kg bw/day Group 3 - 250 mg/kg bw/day 

54 

A.M. 

Group 4 - 750 mg/kg bw/day 

Page204 
Harlan Study Number: 41205015 Report Page 205 

Appendix2 Individual and Group Mean Body Weights 

Body Weights (g) 

Day Numbers Relative to Start Date 

Group Animal 

(Sex) Number 1 8 15 22 29 36 43 

1 (M) 1 319 336 349 365 375 385 391 

2 310 325 344 347 358 372 387 

3 310 320 336 343 354 378 385 

4 315 334 355 373 393 400 409 

5 318 332 343 365 378 391 406 

6 316 332 344 353 362 369 379 

7 328 347 362 369 384 392 405 

8 306 317 329 339 345 345 346 

9 325 346 363 374 391 405 417 

10 312 323 338 344 353 366 374 

11 331 355 372 363 387 397 410 

12 315 331 342 350 369 381 391 - --- --- --- --- --- --- -- Mean 317 .1 333.2 348.1 357 .1 370.8 381.8 391.7 

S.D. 7.6 11 . 5 12.6 12.5 16.3 17.0 19.7 

N 12 12 12 12 12 12 12 

Dose Levels: Group 1 - O (Control) Group 2 - 50 mg/kg bw/day Group 3 - 250 mg/kg bw/day Group 4 - 750 mg/kg bw/day 
Harlan Study Number: 41205015 Report Page206 

Appendix 2 ( continued) Individual and Group Mean Body Weights 

Body Weights (g) 

Day Numbers Relative to Start Date 

Group Animal 

(Sex) Number 1 8 15 22 29 36 43 

2(M) 25 316 336 346 361 378 381 389 

26 313 334 354 362 374 390 403 

27 308 320 327 334 348 357 374 

28 303 310 316 323 332 343 349 

29 327 352 371 386 387 404 417 

30 316 337 345 355 367 378 393 

31 298 307 317 334 347 348 358 

32 336 353 360 365 379 390 414 

33 326 350 367 381 386 387 390 

34 327 339 352 342 366 385 404 

35 306 330 338 329 357 372 383 

36 317 333 340 339 355 369 371 - -- -- -- -- -- -- -- Mean 316.1 333.4 344.4 350.9 364.7 375.3 387.1 

S.D. 11.3 15 .1 17.9 20.5 17.2 18.3 21.2 

N 12 12 12 12 12 12 12 

Dose Levels: Group 1 - o (Control) Group 2 - 50 mg/kg bw/day Group 3 - 250 mg/kg bw/day Group 4 - 750 mg/kg bw/day 
Harlan Study Number: 41205015 Report Page207 

Appendix 2 ( continued) Individual and Group Mean Body Weights 

Body Weights (g) 

Day Numbers Relative to Start Date 

Group Animal 

(Sex) Number 1 8 15 22 29 36 43 

3(M) 49 320 330 332 343 348 341 348 

50 325 338 355 367 374 375 387 

51 326 345 360 376 381 381 393 

52 350 370 388 399 424 436 440 

53 323 345 361 372 394 406 424 

54 316 336 343 359 369 376 384 

55 316 332 348 357 372 378 386 

56 314 329 343 350 367 378 389 

57 314 325 334 347 362 373 382 

58 305 317 323 330 342 351 357 

59 310 329 339 350 366 368 378 

60 320 334 353 364 386 399 408 --- -- --- --- -- -- -- --- Mean 319.9 335.8 348.3 359.5 373.8 380.2 389.7 

S.D. 11.3 13.3 17.0 18.0 21.5 24.8 25.4 

N 12 12 12 12 12 12 12 

Dose Levels: Group 1 - O (Control) Group 2 - 50 mg/kg bw/day Group 3 - 250 mg/kg bw/day Group 4 - 750 mg/kg bw/day 
Harlan Study Number: 41205015 Report Page 208 

Appendix 2 ( continued) Individual and Group Mean Body Weights 

Body Weights (g) 

Day Numbers Relative to Start Date 

Group Animal 

(Sex) Number 1 8 15 22 29 36 43 

4(M) 73 300 319 312 326 346 358 368 

74 323 335 342 343 351 357 365 

75 323 331 353 352 367 367 383 

76 312 321 332 338 351 357 366 

77 313 317 330 348 369 385 394 

78 327 330 341 354 364 383 401 

79 311 323 333 342 348 358 370 

80 335 356 372 376 382 391 401 

81 316 331 324 335 347 358 370 

82 302 300 309 324 340 337 349 

83 320 335 338 357 359 362 374 

84 319 323 345 360 359 367 386 --- --- --- --- --- --- --- Mean 316.8 326.8 335.9 346.3 356.9 365.0 377.3 

S.D. 10.0 13.4 17.2 14.8 12.0 15.0 15.9 

N 12 12 12 12 12 12 12 

Dose Levels: Group 1 - o (Control) Group 2 - 50 mg/kg bw/day Group 3 - 250 mg/kg bw/day Group 4 - 750 mg/kg bw/day 
Harlan Study Number: 41205015 

Appendix 2 ( continued) 

Report 

Individual and Group Mean Body Weights 

Body Weights (g) 

Day Numbers Relative to Start Date 

Group Animal 

(Sex) Number 1 8 15 

1 (F) 13 210 218 225 

14 202 208 213 

15 199 202 211 

16 218 219 223 

17 208 206 215 

18 218 220 221 

19 219 225 230 

20 215 214 227 

21 211 217 227 

22 204 216 220 

23 209 216 221 

24 207 209 210 --- --- --- --- Mean 210.0 214.2 220.3 

S.D. 6.5 6.6 6.7 

N 12 12 12 

Dose Levels: Group 1 - o (Control) Group 2 - 50 mg/kg bw/day Group 3 - 250 mg/kg bw/day 

Page 209 

Group 4 - 750 mg/kg bw/day 
Harlan Study Number: 41205015 

Appendix 2 ( continued) 

Report 

Individual and Group Mean Body Weights 

Body Weights (g) 

Day Numbers Relative to Start Date 

Group Animal 

(Sex) Number 1 8 15 

2(F) 37 210 213 217 

38 206 209 205 

39 204 213 223 

40 210 215 219 

41 212 211 222 

42 201 198 204 

43 214 217 221 

44 217 226 234 

45 210 219 232 

46 215 224 229 

47 202 209 217 

48 215 220 222 --- --- --- -- Mean 209.7 214.5 220.4 

S.D. 5.3 7.6 9.2 

N 12 12 12 

Dose Levels: Group 1 - o (Control) Group 2 - 50 mg/kg bw/day Group 3 - 250 mg/kg bw/day 

Page 210 

Group 4 - 750 mg/kg bw/day 
Harlan Study Number: 41205015 

Appendix 2 ( continued) 

Report 

Individual and Group Mean Body Weights 

Body Weights (g) 

Day Numbers Relative to Start Date 

Group Animal 

(Sex) Number 1 8 15 

3(F) 61 206 206 211 

62 210 215 218 

63 209 205 216 

64 205 206 210 

65 205 207 211 

66 199 200 208 

67 214 219 223 

68 211 204 212 

69 204 205 209 

70 209 213 220 

71 212 220 226 

72 206 211 213 - --- --- --- Mean 207.5 209.3 214.8 

S.D. 4.1 6.3 5.8 

N 12 12 12 

Dose Levels: Group 1 - o (Control) Group 2 - 50 mg/kg bw/day Group 3 - 250 mg/kg bw/day 

Page 211 

Group 4 - 750 mg/kg bw/day 
Harlan Study Number: 41205015 Report Page 212 

Appendix 2 ( continued) Individual and Group Mean Body Weights 

Body Weights (g) 

Day Numbers Relative to Start Date 

Group Animal 

(Sex) Number 1 8 15 

4(F) 85 222 220 229 

86 211 211 216 

87 206 202 203 

88 198 194 201 

89 201 204 208 

90 215 214 213 

91 213 216 221 

92 220 222 230 

93 212 207 204 

94 212 212 225 

95 206 208 208 

96 217 224 232 --- --- --- --- Mean 211 .1 211.2 215.8 

S.D. 7.3 8.8 11 . 3 

N 12 12 12 

Dose Levels: Group 1 - O (Control) Group 2 - 50 mg/kg bw/day Group 3 - 250 mg/kg bw/day Group 4 - 750 mg/kg bw/day 
Harlan Study Number: 41205015 Report Page 213 

Appendix 2 ( continued) Individual and Group Mean Body Weights 

Body Weights (g) Day 

Group Animal After Mating (Sex) Number Lactation 

0 7 14 20 1 4 

1 (F) 13 225 250 276 334 234 256 

14 212 237 258 316 235 240 

15 NP 210 234 230 244 

16 227 257 286 357 248 266 

17 214 247 275 344 239 251 

18 235 269 290 368 263 281 

19 236 254 277 339 252 275 

20 225 258 284 336 254 266 

21 227 246 268 329 230 252 

22 223 248 272 323 258 272 

23 218 244 267 330 218 245 

24 211 236 258 321 218 245 

Mean 223.0 249.6 273.7 336.1 240.8 259.0 

S.D. 8.5 9.6 10.6 15.6 15.4 13.7 

N 11 11 11 11 11 11 

Dose Levels: Group 1 - O(Control) Group 2 - 50 mg/kg bw/day Group 3 - 250 mg/kg bw/day Group 4 - 750 mg/kg bw/day 
Harlan Study Number: 41205015 Report Page 214 

Appendix 2 ( continued) Individual and Group Mean Body Weights 

Body Weights (g) Day 

Group Animal After Mating Lactation (Sex) Number 

0 7 14 20 1 4 

2(F) 37 219 246 271 347 252 260 

38 219 256 275 341 252 260 

39 NP 223 252 257 249 

40 218 252 281 331 255 259 

41 NP 218 252 246 245 

42 203 234 255 326 229 220 

43 224 248 274 350 237 262 

44 231 277 314 389 292 304 

45 231 265 301 372 294 287 

46 231 262 279 352 243 268 

47 NP 215 240 243 237 

48 222 257 276 338 239 257 

Mean 222.0 255.2 280.7 349.6 254.8 264.1 

S.D. 9.0 12.3 17.2 19.9 23.2 22.9 

N 9 9 9 9 9 9 

Dose Levels: Group 1 - O(Control) Group 2 - 50 mg/kg bw/day Group 3 - 250 mg/kg bw/day Group 4 - 750 mg/kg bw/day 
Harlan Study Number: 41205015 Report Page 215 

Appendix 2 ( continued) Individual and Group Mean Body Weights 

Body Weights (g) Day 

Group Animal After Mating (Sex) Number Lactation 

0 7 14 20 1 4 

3(F) 61 216 244 273 323 252 260 

62 229 258 281 352 247 262 

63 210 246 264 315 241 258 

64 210 246 266 336 245 251 

65 213 234 265 327 244 246 

66 208 233 253 307 287 241 

67 229 263 285 358 262 281 

68 208 238 262 324 235 241 

69 207 238 256 315 236 250 

70 219 244 273 337 234 260 

71 232 263 291 345 278 285 

72 218 241 263 324 245 259 

Mean 216.6 245.7 269.3 330.3 250.5 257.8 

S.D. 9.0 10.4 11 . 6 15.6 16.9 13.9 

N 12 12 12 12 12 12 

Dose Levels: Group 1 - O(Control) Group 2 - 50 mg/kg bw/day Group 3 - 250 mg/kg bw/day Group 4 - 750 mg/kg bw/day 
Harlan Study Number: 41205015 Report Page 216 

Appendix 2 ( continued) Individual and Group Mean Body Weights 

Body Weights (g) Day 

Group Animal 

(Sex) Number After Mating Lactation 

0 7 14 20 1 4 

4(F) 85 225 258 279 341 270 266 

86 212 250 280 339 255 268 

87 NP 202 224 232 228 

88 201 235 270 336 256 253 

89 211 231 255 328 241 250 

90 257 276 315 385 272 293 

91 225 252 283 348 258 259 

92 230 261 290 359 272 265 

93 245 258 279 343 262 265 

94 224 258 284 357 266 274 

95 204 233 256 311 226 239 

96 224 259 285 349 251 250 

Mean 223.5 251.9 279.6 345.1 257.2 262.0 

S.D. 16.8 13.8 16.4 18.8 14 .1 14.4 

N 11 11 11 11 11 11 

Dose Levels: Group 1 - O(Control) Group 2 - 50 mg/kg bw/day Group 3 - 250 mg/kg bw/day Group 4 - 750 mg/kg bw/day 
Harlan Study Number: 41205015 Report Page 217 

Appendix3 Individual and Group Mean Body Weight Gains 

Increase in Body Weight (g) 

Day Numbers Relative to Start Date 

Group Animal From: 1 8 15 22 29 36 

(Sex) Number To: 8 15 22 29 36 43 

1 (M) 1 17 13 16 10 10 6 

2 15 19 3 11 14 15 

3 10 16 7 11 24 7 

4 19 21 18 20 7 9 

5 14 11 22 13 13 15 

6 16 12 9 9 7 10 

7 19 15 7 15 8 13 

8 11 12 10 6 0 1 

9 21 17 11 17 14 12 

10 11 15 6 9 13 8 

11 24 17 -9 24 10 13 

12 16 11 8 19 12 10 -- -- -- -- -- -- Mean 16 .1 14.9 9.0 13.7 11 .o 9.9 

S.D. 4.3 3.2 7.9 5.4 5.7 4 .1 

N 12 12 12 12 12 12 

Dose Levels: Group 1 - o (Control) Group 2 - 50 mg/kg bw/day Group 3 - 250 mg/kg bw/day Group 4 - 750 mg/kg,bw/day 
Harlan Study Number: 41205015 Report Page 218 

Appendix 3 ( continued) Individual and Group Mean Body Weight Gains 

Increase in Body Weight (g) 

Day Numbers Relative to Start Date 

Group Animal From: 1 8 15 22 29 36 

(Sex) Number To: 8 15 22 29 36 43 

2(M) 25 20 10 15 17 3 8 

26 21 20 8 12 16 13 

27 12 7 7 14 9 17 

28 7 6 7 9 11 6 

29 25 19 15 1 17 13 

30 21 8 10 12 11 15 

31 9 10 17 13 1 10 

32 17 7 5 14 11 24 

33 24 17 14 5 1 3 

34 12 13 -10 24 19 19 

35 24 8 -9 28 15 11 

36 16 7 -1 16 14 2 -- -- -- -- -- - Mean 17.3 11.0 6.5 13.8 10.7 11.8 

S.D. 6.2 5.0 9.0 7.3 6.2 6.5 

N 12 12 12 12 12 12 

Dose Levels: Group 1 - o (Control) Group 2 - 50 mg/kg bw/day Group 3 - 250 mg/kg bw/day Group 4 - 750 mg/kg bw/day 
Harlan Study Number: 41205015 Report Page 219 

Appendix 3 ( continued) Individual and Group Mean Body Weight Gains 

Increase in Body Weight (g) 

Day Numbers Relative to Start Date 

Group Animal From: 1 B 15 22 29 36 

(Sex) Number To: 8 15 22 29 36 43 

3(M) 49 10 2 11 5 -7 7 

50 13 17 12 7 1 12 

51 19 15 16 5 0 12 

52 20 18 11 25 12 4 

53 22 16 11 22 12 18 

54 20 7 16 10 7 8 

55 16 16 9 15 6 8 

56 15 14 7 17 11 11 

57 11 9 13 15 11 9 

58 12 6 7 12 9 6 

59 19 10 11 16 2 10 

60 14 19 11 22 13 9 -- -- -- -- -- -- Mean 15.9 12.4 11.3 14.3 6.4 9.5 

S.D. 4.0 5.5 2.9 6.7 6.2 3.6 

N 12 12 12 12 12 12 

Dose Levels: Group 1 - o (Control) Group 2 - 50 mg/kg bw/day Group 3 - 250 mg/kg bw/day Group 4 - 750 mg/kg bw/day 
Harlan Study Number: 41205015 Report Page 220 

Appendix 3 ( continued) Individual and Group Mean Body Weight Gains 

Increase in Body Weight (g) 

Day Numbers Relative to Start Date 

Group Animal From: 1 8 15 22 29 36 

(Sex) Number To: 8 15 22 29 36 43 

4(M) 73 19 -7 14 20 12 10 

74 12 7 1 8 6 8 

75 8 22 -1 15 0 16 

76 9 11 6 13 6 9 

77 4 13 18 21 16 9 

78 3 11 13 10 19 18 

79 12 10 9 6 10 12 

80 21 16 4 6 9 10 

81 15 -7 11 12 11 12 

82 -2 9 15 16 -3 12 

83 15 3 19 2 3 12 

84 4 22 15 -1 8 19 -- -- -- -- -- - Mean 10.0 9.2 10.3 10.7 8.1 12.3 

S.D. 6.9 9.4 6.6 6.8 6.3 3.6 

N 12 12 12 12 12 12 

Dose Levels: Group 1 - O (Control) Group 2 - 50 mg/kg bw/day Group 3 - 250 mg/kg bw/day Group 4 - 750 mg/kg bw/day 
Harlan Study Number: 41205015 Report Page 221 

Appendix 3 ( continued) Individual and Group Mean Body Weight Gains 

Increase in Body Weight (g) 

Day Numbers Relative to Start Date 

Group Animal From: 1 8 

(Sex) Number To: 8 15 

1 ( F) 13 8 7 

14 6 5 

15 3 9 

16 1 4 

17 -2 9 

18 2 1 

19 6 5 

20 -1 13 

21 6 10 

22 12 4 

23 7 5 

24 2 1 -- Mean 4.2 6 .1 

S.D. 4.0 3.6 

N 12 12 

Dose Levels: Group 1 - O (Control) Group 2 - 50 mg/kg bw/day Group 3 - 250 mg/kg bw/day Group 4 - 750 mg/kg bw/day 
Harlan Study Number: 41205015 Report Page 222 

Appendix 3 ( continued) Individual and Group Mean Body Weight Gains 

Increase in Body Weight (g) 

Day Numbers Relative to Start Date 

Group Animal From: 1 8 

(Sex) Number To: 8 15 

2(F) 37 3 4 

38 3 -4 

39 9 10 

40 5 4 

41 -1 11 

42 -3 6 

43 3 4 

44 9 8 

45 9 13 

46 9 5 

47 7 8 

48 5 2 

-- -- Mean 4.8 5.9 

S.D. 4.0 4.5 

N 12 12 

Dose Levels: Group 1 - o (Control) Group 2 - 50 mg/kg bw/day Group 3 - 250 mg/kg bw/day Group 4 - 750 mg/kg bw/day 
Harlan Study Number: 41205015 Report Page 223 

Appendix 3 ( continued) Individual and Group Mean Body Weight Gains 

Increase in Body Weight (g) 

Day Numbers Relative to Start Date 

Group Animal From: 1 8 

(Sex) Number To: 8 15 

3(F) 61 0 5 

62 5 3 

63 -4 11 

64 1 4 

65 2 4 

66 1 8 

67 5 4 

68 -7 8 

69 1 4 

70 4 7 

71 8 6 

72 5 2 - Mean 1.8 5.5 

S.D. 4.2 2.6 

N 12 12 

Dose Levels: Group 1 - o (Control) Group 2 - 50 mg/kg bw/day Group 3 - 250 mg/kg bw/day Group 4 - 750 mg/kg bw/day 
Harlan Study Number: 41205015 Report Page 224 

Appendix 3 ( continued) Individual and Group Mean Body Weight Gains 

Increase in Body Weight (g) 

Day Numbers Relative to Start Date 

Group Animal From: 1 8 

(Sex) Number To: 8 15 

4(F) 85 -2 9 

86 0 5 

87 -4 1 

88 -4 7 

89 3 4 

90 -1 -1 

91 3 5 

92 2 8 

93 -5 -3 

94 0 13 

95 2 0 

96 7 8 -- - Mean 0 .1 4.7 

S.D. 3.5 4.7 

N 12 12 

Dose Levels: Group 1 - o (Control) Group 2 - 50 mg/kg bw/day Group 3 - 250 mg/kg bw/day Group 4 - 750 mg/kg bw/day 
Harlan Study Number: 41205015 Report Page 225 

Appendix 3 ( continued) Individual and Group Mean Body Weight Gains 

Increase in Body Weight (g) Cumulative Body Weight Change (g) 

Days Days 

After Mating Lactation After Mating 

Group Animal From: 0 7 14 1 0 0 

(sex) Number To: 7 14 20 4 14 20 

1 (F) 13 25 26 58 22 51 109 

14 25 21 58 5 46 104 

15 NP 24 -4 14 20 34 

16 30 29 71 18 59 130 

17 33 28 69 12 61 130 

18 34 21 78 18 55 133 

19 18 23 62 23 41 103 

20 33 26 52 12 59 111 

21 19 22 61 22 41 102 

22 25 24 51 14 49 100 

23 26 23 63 27 49 112 

24 25 22 63 27 47 110 ---

Mean 26.6 24 .1 62.4 18.2 50.7 113. 1 

S.D. 5.4 2.8 8.0 6.9 7.0 12.2 

N 11 11 11 11 11 11 

Dose Levels: Group 1 - O(Control) Group 2 - 50 mg/kg bw/day Group 3 - 250 mg/kg bw/day Group 4 - 750 mg/kg bw/day 
Harlan Study Number: 41205015 Report Page 226 

Appendix 3 ( continued) Individual and Group Mean Body Weight Gains 

Increase in Body Weight (g) Cumulative Body Weight Change (g) 

Days Days 

After Mating Lactation After Mating 

Group Animal From: 0 7 14 1 0 0 

(sex) Number To: 7 14 20 4 14 20 

2(F) 37 27 25 76 8 52 128 

38 37 19 66 8 56 122 

39 NP 29 5 -8 34 26 

40 34 29 50 4 63 113 

41 NP 34 -6 - 1 28 27 

42 31 21 71 -9 52 123 

43 24 26 76 25 50 126 

44 46 37 75 12 83 158 

45 34 36 71 -7 70 141 

46 31 17 73 25 48 121 

47 NP 25 3 -6 28 22 

48 35 19 62 18 54 116 ---

Mean 33.2 25.4 68.9 9.3 58.7 127.6 

S.D. 6.3 7.4 8.5 12.3 11. 4 13.9 

N 9 9 9 9 9 9 

Dose Levels: Group 1 - O(Control) Group 2 - 50 mg/kg bw/day Group 3 - 250 mg/kg bw/day Group 4 - 750 mg/kg bw/day 
Harlan Study Number: 41205015 Report Page 227 

Appendix 3 ( continued) Individual and Group Mean Body Weight Gains 

Increase in Body Weight (g) Cumulative Body Weight Change (g) 

Days Days 

After Mating Lactation After Mating 

Group Animal From: 0 7 14 1 0 0 

(sex) Number To: 7 14 20 4 14 20 

3(F) 61 28 29 50 8 57 107 

62 29 23 71 15 52 123 

63 36 18 51 17 54 105 

64 36 20 70 6 56 126 

65 21 31 62 2 52 114 

66 25 20 54 -46 45 99 

67 34 22 73 19 56 129 

68 30 24 62 6 54 116 

69 31 18 59 14 49 108 

70 25 29 64 26 54 118 

71 31 28 54 7 59 113 

72 23 22 61 14 45 106 --

Mean 29 .1 23.7 60.9 7.3 52.8 113. 7 

S.D. 4.9 4.5 7.7 18 .1 4.5 9.2 

N 12 12 12 12 12 12 

Dose Levels: Group 1 - O(Control) Group 2 - 50 mg/kg bw/day Group 3 - 250 mg/kg bw/day Group 4 - 750 mg/kg bw/day 
Harlan Study Number: 41205015 Report Page 228 

Appendix 3 ( continued) Individual and Group Mean Body Weight Gains 

Increase in Body Weight (g) Cumulative Body Weight Change (g) 

Days Days 

After Mating Lactation After Mating 

Group Animal From: 0 7 14 1 0 0 

(sex) Number To: 7 14 20 4 14 20 

4(F) 85 33 21 62 -4 54 116 

86 38 30 59 13 68 127 

87 NP 22 8 -4 30 26 

88 34 35 66 -3 69 135 

89 20 24 73 9 44 117 

90 19 39 70 21 58 128 

91 27 31 65 1 58 123 

92 31 29 69 -7 60 129 

93 13 21 64 3 34 98 

94 34 26 73 8 60 133 

95 29 23 55 13 52 107 

96 35 26 64 -1 61 125 

Mean 28.5 27.7 65.5 4.8 56.2 121 .6 

S.D. 7.9 5.7 5.6 8.7 10 .1 11.3 

N 11 11 11 11 11 11 

Dose Levels: Group 1 - O(Control) Group 2 - 50 mg/kg bw/day Group 3 - 250 mg/kg bw/day Group 4 - 750 mg/kg bw/day 
Harlan Study Number: 41205015 Report Page 229 

Appendix 4 Individual and Group Mean Food Consumption Values for Females Following Mating and During Lactation 

Mean Food Consumption (g/rat/day) 

After Mating Lactation 

Group Animal From: 0 7 14 1 

(Sex) Number To: 7 14 20 4 

1 ( F) 13 18 20 23 25 

14 17 20 22 22 

15 NP 19 18 17 

16 18 22 24 23 

17 18 22 25 20 

18 19 23 24 31 

19 17 19 23 29 

20 19 21 23 21 

21 17 20 22 27 

22 18 20 22 31 

23 16 19 20 26 

24 18 20 22 34 

Mean 18.0 20.6 22.6 26.3 

S.D. 0.8 1 .6 1 .9 4.5 

N 11 11 11 11 

Dose Levels: Group 1 - O(Control) Group 2 - 50 mg/kg bw/day Group 3 - 250 mg/kg bw/day Group 4 - 750 mg/kg bw/day 
Harlan Study Number: 41205015 Report Page 230 

Appendix 4 ( continued) Individual and Group Mean Food Consumption Values for Females Following Mating and During 

Lactation 

Mean Food Consumption (g/rat/day) 

After Mating Lactation 

Group Animal From: 0 7 14 1 

(Sex) Number To: 7 14 20 4 

2(F) 37 19 21 26 24 

38 19 24 25 26 

39. NP 18 22 15 

40 18 23 22 17 

41 NP 20 17 15 

42 17 21 22 11 

43 19 21 25 37 

44 22 28 27 32 

45 22 26 27 21 

46 20 22 25 33 

47 NP 17 19 16 

48 18 21 22 25 

Mean 19.6 22.9 24.5 25.0 

S.D. 1. 7 2.5 2.0 8.3 

N 9 9 9 9 

Dose Levels: Group 1 - O(Control) Group 2 - 50 mg/kg bw/day Group 3 - 250 mg/kg bw/day Group 4 - 750 mg/kg bw/day 
Harlan Study Number: 41205015 Report Page 231 

Appendix 4 ( continued) Individual and Group Mean Food Consumption Values for Females Following Mating and During 

Lactation 

Mean Food Consumption (g/rat/day) 

After Mating Lactation 

Group Animal From: 0 7 14 1 

(Sex) Number To: 7 14 20 4 

3(F) 61 19 24 25 23 

62 20 24 23 28 

63 20 20 21 30 

64 20 22 25 24 

65 15 21 21 20 

66 16 19 21 18 

67 19 21 26 34 

68 16 19 23 19 

69 17 21 22 26 

70 17 21 23 23 

71 20 23 25 27 

72 17 22 25 30 

Mean 18.0 21.3 23.2 25 .1 

S.D. 1.9 1.8 1.8 5.0 

N 12 12 12 12 

Dose Levels: Group 1 - O(Control) Group 2 - 50 mg/kg bw/day Group 3 - 250 mg/kg bw/day Group 4 - 750 mg/kg bw/day 
Harlan Study Number: 41205015 Report Page 232 

Appendix 4 ( continued) Individual and Group Mean Food Consumption Values for Females Following Mating and During 

Lactation 

Mean Food Consumption (g/rat/day) 

After Mating Lactation 

Group Animal From: 0 7 14 1 

(Sex) Number To: 7 14 20 4 

4(F) 85 19 22 23 21 

86 18 21 22 25 

87 NP 15 18 12 

88 18 23 25 19 

89 14 21 23 25 

90 20 25 26 37 

91 19 23 25 26 

92 20 25 24 18 

93 16 21 24 29 

94 21 22 26 30 

95 16 19 20 25 

96 20 21 23 17 

Mean 18.5 21.9 23.7 24.6 

S.D. 2.8 3.6 5.1 6.0 

N 11 11 11 11 

Dose Levels: Group 1 - O(Control) Group 2 - 50 mg/kg bw/day Group 3 - 250 mg/kg bw/day Group 4 - 750 mg/kg bw/day 
Harlan Study Number: 41205015 Report Page 233 

Appendix 5 Individual Mating Performance, Fertility and Gestation Lengths 

Group: 1 Dose Level: o (Control) 

Paired Animal Number Pre-Coital Interval 

(Days) Copulation Plug Count Sperm Reading Score Pregnancy Status Gestation Length (Days) 

13 F 1 M 2 5 PT 3+ p 22:\, 

14 F 2 M 2 5 PT H 3+ p 22:\, 

15 F 3 M 2 4 PT H 1+ NP 

16 F 4 M 3 6 PT H 3+ p 23\ 

17 F 5 M 1 3 PT 3+ p 22:\, 

18 F 6 M 4 4 PT 2+ p 22:\, 

19 F 7 M 3 3 PT H PV 3+ p 23:\, 

20 F 8 M 1 5 PT H 3+ p 22\ 

21 F 9 M 2 4 PT 3+ p 22:\, 

22 F 10 M 2 5 PT H 2+ p 23:\, 

23 F 11 M 2 6 PT H 3+ p 23 

24 F 12 M 3 6 PT H 3+ p 23 
Harlan Study Number: 41205015 Report Page 234 

Appendix 5 ( continued) Individual Mating Performance, Fertility and Gestation Lengths 

Group: 2 Dose Level: 50 mg/kg bw/day 

Paired Animal Number Pre-Coital Interval 

(Days) Copulation Plug Count Sperm Reading Score Pregnancy Status Gestation Length (Days) 

37 F 25 M 3 4 PT H 3+ p 22\ 

38 F 26 M 4 5 PT 1+ NP 22\ 

39 F 27 M 2 1 PT H 3+ p 

40 F 28 M 2 5 PT H 3+ p 22\ 

41 F 29 M 1 3 PT 2+ NP 

42 F 30 M 1 1 PT H 1+ p 22\ 

43 F 31 M 3 4 PT 1+ p 23\ 

44 F 32 M 3 4 PT H 3+ p 23\ 

45 F 33 M 2 7 PT H 3+ p 22\ 

46 F 34 M 2 6 PT 3+ p 22\ 

47 F 35 M 3 6 PT H 3+ NP 

48 F 36 M 3 3 PT H PV 3+ p 22\ 
Harlan Study Number: 41205015 Report Page 235 

Appendix 5 ( continued) Individual Mating Performance, Fertility and Gestation Lengths 

Group: 3 Dose Level: 250 mg/kg bw/day 

Paired Animal Number Pre-Coital Interval Copulation Plug Count (Days) Sperm Reading Score Pregnancy Status Gestation Length (Days) 

61 F 49 M 3 6 PT H 3+ p 221r; 

62 F 50 M 4 7 PT H 3+ p 231r; 

63 F 51 M 1 3 PT 3+ p 23 

64 F 52 M 3 4 PT H 3+ p 221r; 

65 F 53 M 3 5 PT H 3+ p 221r; 

66 F 54 M 1 3 PT 3+ p 221r; 

67 F 55 M 4 7 PT 3+ p 221r; 

68 F 56 M 1 4 PT 3+ p 22 

69 F 57 M 3 5 PT 3+ p 221r; 

70 F 58 M 2 3 PT 3+ p 221r; 

71 F 59 M 3 3 PT 3+ p 221r; 

72 F 60 M 4 8 PT H 2+ p 231r; 
Harlan Study Number: 41205015 Report Page236 

Appendix 5 ( continued) Individual Mating Performance, Fertility and Gestation Lengths 

Group: 4 Dose Level: 750 mg/kg bw/day 

Paired Animal Number Pre-Coital Interval Copulation Plug Count Sperm Reading Score Pregnancy Status Gestation Length (Days) (Days) 

85 F 73 M 1 1 PT H 3+ p 221:; 

86 F 74 M 3 3 PT 3+ p 221:; 

87 F 75 M 1 4 PT H 2+ NP 

88 F 76 M 1 2 PT 2+ p 221:; 

89 F 77 M 2 2 PT 2+ p 221:; 

90 F 78 M 13 3 PT H 2+ p 221:; 

91 F 79 M 3 5 PT H 3+ p 221:; 

92 F 80 M 1 4 PT H 3+ p 231:; 

93 F 81 M 12 6 PT H 3+ p 221:; 

94 F 82 M 1 3 PT H 2+ p 221:; 

95 F 83 M 3 6 PT H 3+ p 231:; 

96 F 84 M 2 5 PT 3+ p 221:; 
Harlan Study Number: 41205015 Report Page237 

Appendix 6 Individual and Group Mean Litter Size and Litter Weights 

Group: 1 Dose Level: O(Control) 

Number of Live Litter Weight Mean Offspring Weight Mean Offspring 

Number Total Body Weight Change Number of Offspring (g) (g) Animal/Litter of Implantation Number of (g) 

Number Corpora Sites Offspring Day 1 Day 4 Days 1-4 

Lutea Born Day 1 Day 4 Day 1 Day 4 

Males Females Males Females Males Females 

13 12 12 12 11 11 62.4 91.6 5.7 5.6 8.4 8.3 2.7 2.6 

14 17 13 11 11 11 58.9 78.8 5.6 5.2 7.4 7.0 1.9 1.8 

15 NP 4 

16 14 14 12 12 12 76.3 100.8 6.4 6.3 8.4 8.4 2.0 2.2 

17 14 13 13 13 12 74.0 95.9 6.0 5.3 8.2 7.6 2.2 2.3 

18 16 16 15 15 15 81.1 114.3 5.5 5.3 7.6 7.6 2.2 2.3 

19 12 12 11 11 10 71.4 92.5 6.7 6.2 9.3 9.2 2.6 3.0 

20 12 11 10 9 9 53.3 79.3 6.6 5.7 9.0 8.8 2.5 3.0 

21 15 15 13 13 13 67.5 95.6 5.3 5 .1 7.5 7.3 2.2 2.2 

22 11 10 9 9 9 58.4 88.7 6.6 6.4 9.8 10.0 3.2 3.6 

23 15 15 13 12 11 59.3 85.6 5.1 4.8 8.0 7.5 2.9 2.7 

24 16 13 13 13 13 - 72.4 101 .4 5.6 5.6 7.8 7.9 2.2 2.3 

Mean 14.0 13 .1 12.0 11. 7 11.5 66.82 93.14 5.90 5.59 8.30 8.14 2.40 2.54 

S.D. 2.0 1.8 1. 7 1.8 1.8 8.89 10.32 0.57 0.52 0.77 0.89 0.42 0.50 

N 11 11 11 11 11 11 11 11 11 11 11 11 11 

I 
Harlan Study Number: 41205015 Report Page 238 

Appendix 6 ( continued) Individual and Group Mean Litter Size and Litter Weights 

Group: 2 Dose Level: 50 mg/kg bw/day 

Number of Live Litter Weight Mean Offspring Weight Mean Offspring 

Number Total Body Weight Change Number of Offspring (g) (g) Animal/Litter of Implantation Number of (g) 

Number Corpora Sites Offspring Day 1 Day 4 Days 1-4 

Lu tea Born Day 1 Day 4 Day 1 Day 4 

Males Females Males Females Males Females 

37 14 12 12 12 12 73.8 103.0 6.4 6.0 9.0 8.3 2.6 2.3 

38 14 13 12 12 12 71.4 91.8 6.0 5.9 7.8 7.5 1 . 8 1 .6 

39 NP 5 

40 11 10 10 10 10 54.2 75.3 5.3 5.5 7.4 7.6 2 .1 2 .1 

41 NP 

42 14 14 14 14 11 70.9 67.2 5.3 4.9 6.4 5.9 1 . 1 1 .0 

43 14 14 14 14 14 82.6 126.7 5.9 5.9 9.0 9 .1 3 .1 3.2 

44 15 15 14 14 14 88.6 132.0 6.5 6.0 9.7 9.0 3.2 2.9 

45 12 12 12 11 11 66.7 89.5 6.2 5.9 8.4 7.7 2.2 1 .9 

46 15 15 15 15 14 74.9 103.6 5.4 4.7 7.8 7.0 2.4 2.4 

47 NP 

48 13 12 12 12 12 69.8 94.2 5.9 5.7 7.8 7.9 1.9 2.2 

Mean 13.6 13.0 12.8 12.7 12.2 72.54 98.14 5.87 5.60 8 .14 7.77 2.27 2 .17 

S.D. 1. 3 1. 7 1. 6 1. 7 1 .5 9.67 21.29 0.46 0.50 1.00 0.97 0.67 0.65 

N 9 9 9 9 9 9 9 9 9 9 9 9 9 
Harlan Study Number: 41205015 Report Page 239 

Appendix 6 ( continued) Individual and Group Mean Litter Size and Litter Weights 

Group: 3 Dose Level: 250 mg/kg bw/day 

Number of Live Litter Weight Mean Offspring Weight Mean Offspring 

Number Total Body Weight Change Number of Offspring (g) (g) Animal/Litter of Implantation Number of (g) 

Number Corpora Sites Offspring Day 1 Day 4 Days 1-4 

Lu tea Born Day 1 Day 4 Day 1 Day 4 

Males Females Males Females Males Females 

61 14 13 8 8 8 50.5 75 .1 6.5 6.3 9.6 9.3 3 .1 3 .1 

62 14 13 13 13 13 87.6 108.5 6.9 6.2 8.5 8.0 1.6 1. 7 

63 15 12 10 10 10 68.9 101 .8 7.2 6.7 10.8 9.8 3.7 3 .1 

64 14 14 12 12 12 67.0 95 .1 5.7 5.4 8.0 7.9 2.3 2.5 

65 16 15 13 13 13 68.8 94.8 5.3 5.3 7.4 7.2 2.0 2.0 

66 12 11 10 10 10 59.6 79.2 6 .1 5.7 8.0 7.8 1 .9 2 .1 

67 15 13 13 13 13 78.6 116 .3 6.2 5.9 9.6 8.6 3.3 2.6 

68 13 13 11 11 11 60.0 82.3 5.6 5.2 7.6 7.3 2.0 2 .1 

69 14 14 11 11 11 62.7 95.2 6.0 5.6 9.3 8.5 3.3 2.9 

70 12 12 12 12 12 63.7 91 .9 5.4 5.1 7.8 7.4 2.4 2.3 

71 15 14 9 9 9 55.3 81.8 6.2 6 .1 9.2 9 .1 3.0 2.9 

72 14 13 11 11 10 74.6 102 .1 7 .1 6.5 10.3 10 .1 3.3 3.6 --- --- Mean 14.0 13. 1 11.1 11.1 11.0 66.44 93.68 6 .18 5.84 8.83 8.40 2.65 2.56 

S.D. 1 .2 1 . 1 1 .6 1.6 1. 7 10.28 12.44 0.62 0.53 1 .12 0.97 0.69 0.56 

N 12 12 12 12 12 12 12 12 12 12 12 12 12 
Harlan Study Number: 41205015 Report Page 240 

Appendix 6 ( continued) Individual and Group Mean Litter Size and Litter Weights 

Group: 4 Dose Level: 750 mg/kg bw/day 

Number of Live Litter Weight Mean Offspring Weight Mean Offspring 

Number Total Body Weight Change Number of Offspring (g) (g) Animal/Litter of Implantation Number of (g) 

Number Corpora Sites Offspring Day 1 Day 4 Days 1-4 

Lute a Born Day 1 Day 4 Day 1 Day 4 

Males Females Males Females Males Females 

85 13 13 10 10 10 57.3 85.8 6.1 5.6 8.8 8.5 2.8 2.9 

86 15 14 13 13 13 72.5 97 .1 5.7 5.5 7.6 7.4 1.9 1.9 

87 NP 

88 13 12 12 12 11 62.3 89.0 5.4 5.0 8.3 7.9 2.9 2.9 

89 13 12 · 12 12 12 66.1 89.4 5.7 5.0 7.6 7.0 1.9 2.0 

90 18 18 18 18 18 92.0 129.6 5.0 5.1 6.4 7.5 1.4 2.3 

91 14 14 14 14 14 73.5 102.6 5.3 5.2 7.4 7.3 2.1 2.1 

92 12 12 12 12 12 68.7 91.8 5.9 5.6 7.8 7.6 1.9 2.0 

93 14 14 13 13 13 75.8 110 .1 6.0 5.7 8.6 8.4 2.6 2.7 

94 13 13 13 13 13 73.3 98.1 5.7 5.5 7.6 7.4 1 .9 1.9 

95 14 12 11 11 11 68.4 97.6 6.4 6.1 9.2 8.6 2.9 2.5 

96 16 14 14 14 13 74.8 72.3 5.5 5.2 5.6 5.5 0.2 0.3 

Mean 14 .1 13.5 12.9 12.9 12.7 71.34 96.67 5.69 5.41 7.73 7.53 2.04 2.12 

S.D. 1. 7 1.8 2.1 2.1 2.1 8.89 14.66 0.39 0.33 1 .04 0.87 0.79 0.72 

N 11 11 11 11 11 11 11 11 11 11 11 11 11 
Harlan Study Number: 41205015 Report Page 241 

Appendix 7 Individual and Group Mean Implantation Losses and Survival Indices 

Pre- Post - Live 

Group Litter Implantation Implantation Birth Viability 

(Sex) Number Loss (%) Loss (%) Index Index (%) 

(%) 

1 ( F) 13 0 0 92 100 

14 24 15 100 100 

15 NP 

16 0 14 100 100 

17 7 0 100 92 

18 0 6 100 100 

19 0 8 100 91 

20 8 9 90 100 

21 0 13 100 100 

22 9 10 100 100 

23 0 13 92 92 

24 19 0 100 100 --

Mean 6 .1 8.2 97.6 97.7 

S.D. 8.4 5.9 4.1 3.9 

N 11 11 11 11 

Dose Levels: Group 1 - O(Control) Group 2 - 50 mg/kg bw/day Group 3 - 250 mg/kg bw/day Group 4 - 750 mg/kg bw/day 
Harlan Study Number: 41205015 Report Page 242 

Appendix 7 ( continued) Individual and Group Mean Implantation Losses and Survival Indices 

Pre- Post - Live 

Group Litter Implantation Implantation Birth Viability 

(Sex) Number Index Index (%) Loss (%) Loss (%) (%) 

2(F) 37 14 0 100 100 

38 7 8 100 100 

39 NP 100 

40 9 0 100 100 

41 NP 

42 0 0 100 79 

43 0 0 100 100 

44 0 7 100 100 

45 0 0 92 100 

46 0 0 100 93 

47 NP 

48 8 0 100 100 --

Mean 4.2 1.6 99.1 96.9 

S.D. 5.4 3.2 2.8 7.2 

N 9 9 9 9 

Dose Levels: Group 1 - O(Control) Group 2 - 50 mg/kg bw/day Group 3 - 250 mg/kg bw/day Group 4 - 750 mg/kg bw/day 
Harlan Study Number: 41205015 Report Page243 

Appendix 7 ( continued) Individual and Group Mean Implantation Losses and Survival Indices 

Pre- Post - Live 

Group Litter Implantation Implantation Birth Viability 

(Sex) Number Loss (%) Loss (%) Index Index (%) 

(%) 

3(F) 61 7 38 100 100 

62 7 0 100 100 

63 20 17 100 100 

64 0 14 100 100 

65 6 13 100 100 

66 8 9 100 100 

67 13 0 100 100 

68 0 15 100 100 

69 0 21 100 100 

70 0 0 100 100 

71 7 36 100 100 

72 7 15 100 91 --

Mean 6.3 15.0 100.0 99.2 

S.D. 6.0 12.6 0.0 2.6 

N 12 12 12 12 

Dose Levels: Group 1 - O(Control) Group 2 - 50 mg/kg bw/day Group 3 - 250 mg/kg bw/day Group 4 - 750 mg/kg bw/day 
Harlan Study Number: 41205015 Report Page 244 

Appendix 7 ( continued) Individual and Group Mean Implantation Losses and Survival Indices 

Pre- Post - Live 

Group Litter Implantation Implantation Birth Viability 

(Sex) Number Loss (%) Loss (%) Index Index (%) 

(%) 

4(F) 85 0 23 100 100 

86 7 7 100 100 

87 NP 

88 8 0 100 92 

89 8 0 100 100 

90 0 0 100 100 

91 0 0 100 100 

92 0 0 100 100 

93 0 7 100 100 

94 0 0 100 100 

95 14 8 100 100 

96 13 0 100 93 --

Mean 4.4 4.2 100.0 98.6 

S.D. 5.5 7.2 0.0 3 .1 

N 11 11 11 11 

Dose Levels: Group 1 - O(Control) Group 2 - 50 mg/kg bw/day Group 3 - 250 mg/kg bw/day Group 4 - 750 mg/kg bw/day 
Harlan Study Number: 41205015 Report Page 245 

Appendix 8 Individual and Group Mean Sex Ratio Values for Offspring 

Group: 1 Dose Level: o (Control) 

Sex Ratio (Post Partum) Day: 

Litter Number At birth 1 4 

Male Female % Male Male Female % Male Male Female % Male 

13 6 6 50 5 6 45 5 6 45 

14 4 7 36 4 7 36 4 7 36 

15 NP 

16 7 5 58 7 5 58 7 5 58 

17 8 5 62 8 5 62 8 4 67 

18 10 5 67 10 5 67 10 5 67 

19 6 5 55 6 5 55 6 4 60 

20 3 7 30 2 7 22 2 7 22 

21 6 7 46 6 7 46 6 7 46 

22 5 4 56 5 4 56 5 4 56 

23 7 6 54 6 6 50 6 5 55 

24 8 5 62 8 5 62 8 5 62 

Mean 52.2 50.8 52 .1 

S.D. 11. 1 12.9 13.6 

N 11 11 11 
Harlan Study Number: 41205015 Report Page 246 

Appendix 8 ( continued) Individual and Group Mean Sex Ratio Values for Offspring 

Group: 2 Dose Level: 50 mg/kg bw/day 

Sex Ratio (Post Partum) Day: 

Litter Number At birth 1 4 

Male Female % Male Male Female % Male Male Female % Male 

37 5 7 42 5 7 42 5 7 42 

38 6 6 50 6 6 50 6 6 50 

39 NP 

40 3 7 30 3 7 30 3 7 30 

41 NP 

42 6 8 43 6 8 43 5 6 45 

43 8 6 57 8 6 57 8 6 57 

44 9 5 64 9 5 64 9 5 64 

45 7 5 58 7 4 64 7 4 64 

46 7 8 47 7 8 47 7 7 50 

47 NP 

48 6 6 50 6 6 50 6 6 50 

Mean 49.0 49.6 50.2 

S.D. 10.3 11 . 0 10.8 

N 9 9 9 
Harlan Study Number: 41205015 Report Page247 

Appendix 8 ( continued) Individual and Group Mean Sex Ratio Values for Offspring 

Group: 3 Dose Level: 250 mg/kg bw/day 

Sex Ratio (Post Partum) Day: 

Litter Number At birth 1 4 

Male Female % Male Male Female % Male Male Female % Male 

61 2 6 25 2 6 25 2 6 25 

62 10 3 77 10 3 77 10 3 77 

63 4 6 40 4 6 40 4 6 40 

64 7 5 58 7 5 58 7 5 58 

65 7 6 54 7 6 54 7 6 54 

66 7 3 70 7 3 70 7 3 70 

67 5 8 38 5 8 38 5 8 38 

68 6 5 55 6 5 55 6 5 55 

69 2 9 18 2 9 18 2 9 18 

70 8 4 67 8 4 67 8 4 67 

71 2 7 22 2 7 22 2 7 22 

72 6 5 55 6 5 55 6 4 60 

Mean 48.2 48.2 48.7 

S.D. 19.4 19.4 19.6 

N 12 12 12 
Harlan Study Number: 41205015 Report Page 248 

Appendix 8 ( continued) Individual and Group Mean Sex Ratio Values for Offspring 

Group: 4 Dose Level: 750 mg/kg bw/day 

Sex Ratio (Post Partum) Day: 

Litter Number At birth 1 4 

Male Female % Male Male Female % Male Male Female % Male 

85 3 7 30 3 7 30 3 7 30 

86 6 7 46 6 7 46 6 7 46 

87 NP 

88 5 7 42 5 7 42 5 6 45 

89 9 3 75 9 3 75 9 3 75 

90 5 13 28 5 13 28 5 13 28 

91 4 10 29 4 10 29 4 10 29 

92 6 6 50 6 6 50 6 6 50 

93 5 8 38 5 8 38 5 8 38 

94 9 4 69 9 4 69 9 4 69 

95 5 6 45 5 6 45 5 6 45 

96 8 6 57 8 6 57 8 5 62 

Mean 46.3 46.3 47 .1 

S.D. 15.8 15.8 16.0 

N 11 11 11 
Harlan Study Number: 41205015 

Appendix 9 Individual Clinical Signs for Offspring 

Group: 1 Dose Level: o (Control) 

Litter Number 

13 

14 

15 NP 

16 

17 

18 

19 

20 

21 

22 

23 

24 

Affected Offspring Sex and Identity 

1M 

Female 13 

Female 7 

1M 

1M 

Female 10 

Report 

Clin.ical Observation 

Found dead 

No Abnormalities Detected 

No Abnormalities Detected 

Cold, weak, no milk in stomach 

Missing 

No Abnormalities Detected 

Missing 

Small 

Found dead 

No Abnormalities Detected 

No Abnormalities Detected 

Found dead 

Missing 

No Abnormalities Detected 

Page 249 

Day Post Partum 

Pre Day 1 

2 

4 

Pre Day 

1 

Pre Day 

2 
Harlan Study Number: 41205015 Report 

Appendix 9 ( continued) Individual Clinical Signs for Offspring 

Group: 2 Dose Level: 50 mg/kg bw/day 

Litter Number 

37 

38 

39 NP 

40 

41 NP 

42 

43 

44 

45 

46 

47 NP 

48 

Affected Offspring Sex and Identity 

Female 13 Female 14 

Male 5 

Female 7 

1F 

Female a 

Female 11 

Clinical Observation 

No Abnormalities Detected 

No Abnormalities Detected 

No Abnormalities Detected 

Small 

Missing 

Missing 

Physical injury to tail 

No Abnormalities Detected 

No Abnormalities Detected 

Found dead 

Bruised snout 

Found dead 

No Abnormalities Detected 

Page 250 

Day Post Partum 

Pre day 1 - 1 

2 

3 

3-5 

Pre Day 

1-2 

3 
Harlan Study Number: 41205015 Report 

Appendix 9 ( continued) Individual Clinical Signs for Offspring 

Group: 3 Dose Level: 250 mg/kg bw/day 

Litter Number 

61 

62 

63 

64 

65 

66 

67 

68 

69 

70 

71 

72 

Affected Offspring Sex and Identity 

Female 12 

Female 9 

Page 251 

Clinical Observation Day Post Partum 

No Abnormalities Detected 

No Abnormalities Detected 

No Abnormalities Detected 

No Abnormalities Detected 

No Abnormalities Detected 

No Abnormalities Detected 

Small 4-5 

No Abnormalities Detected 

No Abnormalities Detected 

No Abnormalities Detected 

No Abnormalities Detected 

Missing 4 
Harlan Study Number: 41205015 Report 

Appendix 9 ( continued) Individual Clinical Signs for Offspring 

Group: 4 Dose Level: 750 mg/kg bw/day 

Litter Number 

85 

86 

87 NP 

88 

89 

90 

91 

92 

93 

94 

95 

96 

Affected Offspring Sex and Identity 

Female 11 

Female 12 

BM 6F (Whole Litter) 

Female 11 

BM SF (Whole Litter) 

Clinical Observation 

No Abnormalities Detected 

No Abnormalities Detected 

Missing 

No Abnormalities Detected 

No Abnormalities Detected 

No Abnormalities Detected 

No Abnormalities Detected 

No Abnormalities Detected 

No Abnormalities Detected 

No Abnormalities Detected 

Cold 

Small 

Missing 

Small 

Page252 

Day Post Partum 

2 

2 

3 

4 

4-5 
Harlan Study Number: 41205015 Report 

Appendix 10 Individual and Group Mean Reflexological Responses for Offspring 

Group: 1 Dose Level: o (Control) 

Litter 

Number 

13 

14 

15 NP 

16 

17 

18 

19 

20 

21 

22 

23 

24 

-

Mean 

S.D. 

N 

Surface righting 

(Day 1 Post Partum) 

Number of offspring % passed examined passed 

11 11 100 

11 11 100 

12 12 100 

13 13 100 

15 15 100 

11 10 91 

9 8 89 

13 13 100 

9 9 100 

12 12 100 

13 13 100 

98.2 

4.1 

11 

Page 253 
Harlan Study Number: 41205015 Report 

Appendix 10 (continued) Individual and Group Mean Reflexological Responses for Offspring 

Group: 2 Dose Level: 50 mg/kg bw/day 

Litter 

Number 

37 

38 

39 NP 

40 

41 NP 

42 

43 

44 

45 

46 

47 NP 

48 

-

Mean 

S.D. 

N 

Surface righting 

(Day 1 Post Partum) 

Number of offspring 

% passed examined passed 

12 12 100 

12 10 83 

10 10 100 

14 13 93 

14 14 100 

14 13 93 

11 11 100 

15 15 100 

12 12 100 

96.6 

5.8 

9 

Page 254 
Harlan Study Number: 41205015 Report Page 255 

Appendix 10 (continued) Individual and Group Mean Reflexological Responses for Offspring 

Group: 3 Dose Level: 250 mg/kg bw/day 

Surface righting 

Litter (Day 1 Post Partum) 

Number Number of offspring 

examined 

% passed passed 

61 8 8 100 

62 13 13 100 

63 10 9 90 

64 12 12 100 

65 13 13 100 

66 10 10 100 

67 13 13 100 

68 11 11 100 

69 11 11 100 

70 12 12 100 

71 9 9 100 

72 11 11 100 

Mean 99.2 

S.D. 2.9 

N 12 
Harlan Study Number: 41205015 Report 

Appendix 10 (continued) Individual and Group Mean Reflexological Responses for Offspring 

Group: 4 Dose Level: 750 mg/kg bw/day 

Litter 

Number 

85 

86 

87 NP 

88 

89 

90 

91 

92 

93 

94 

95 

96 

-

Mean 

S.D. 

N 

Surface righting 

(Day 1 Post Partum) 

Number of offspring % passed examined passed 

10 9 90 

13 13 100 

12 10 83 

12 12 100 

18 16 89 

14 14 100 

12 11 92 

13 13 100 

13 11 85 

11 11 100 

14 14 100 

94.4 

6.8 

11 

Page 256 
Harlan Study Number: 41205015 Report 

Appendix 11 Individual Necropsy Findings for Offspring 

Group: 1 Dose Level: o (Control) 

Interim Deaths 

Litter Number 

Necropsy Day (Post Offspring Sex & Macroscopic Observation 

13 

14 

15 NP 

16 

17 

18 

19 

20 

21 

22 

23 

24 

Partum) 

Pre Day 1 

Pre Day 1 

Number 

1M Autolytic changes detected 

1M Autolytic changes detected 

Page 257 

Terminal kill 

Total Number Macroscopic Observation of Offspring 

5M 6F No abnormalities detected 

4M 7F No abnormalities detected 

7M 5F No abnormalities detected 

SM 4F No abnormalities detected 

10M 5F No abnormalities detected 

6M 4F No abnormalities detected 

2M 7F No abnormalities detected 

6M 7F No abnormalities detected 

5M 4F No abnormalities detected 

6M 5F No abnormalities detected 

SM 5F No abnormalities detected 
Harlan Study Number: 41205015 Report 

Appendix 11 (continued) Individual Necropsy Findings for Offspring 

Group: 2 Dose Level: 50 mg/kg bw/day 

Litter Number 

37 

38 

39 NP 

40 

41 NP 

42 

43 

44 

45 

46 

47 NP 

48 

Interim Deaths 

Necropsy Day (Post Offspring Sex & 

Partum) Number 

Pre Day 

3 

1F 

Female 11 

Macroscopic Observation 

Autolytic changes detected 

Autolytic changes detected 

Page 258 

Terminal kill 

Total Number Macroscopic Observation of Offspring 

5M 7F No abnormalities detected 

6M 6F No abnormalities detected 

3M 7F No abnormalities detected 

Female 7 Physical injury to tail 

5M 5F No abnormalities detected 

SM 6F No abnormalities detected 

9M 5F No abnormalities detected 

7M 4F No abnormalities detected 

7M 7F No abnormalities detected 

6M 6F No abnormalities detected 
Harlan Study Number: 41205015 Report 

Appendix 11 (continued) Individual Necropsy Findings for Offspring 

Group: 3 Dose Level: 250 mg/kg bw/day 

Litter Number 

61 

62 

63 

64 

65 

66 

67 

68 

69 

70 

71 

72 

Interim Deaths 

Necropsy Day (Post Offspring Sex & 

Partum) Number Macroscopic Observation 

Page 259 

Terminal kill 

Macroscopic Observation Total Number 

of Offspring 

2M 6F No abnormalities detected 

9M 4F No abnormalities detected 

4M 6F No abnormalities detected 

7M SF No abnormalities detected 

7M 6F No abnormalities detected 

7M 3F No abnormalities detected 

Female 12 Small 

SM 7F No abnormalities detected 

6M SF No abnormalities detected 

2M 9F No abnormalities detected 

8M 4F No abnormalities detected 

2M 7F No abnormalities detected 

6M 4F No abnormalities detected 
Harlan Study Number: 41205015 Report 

Appendix 11 (continued) Individual Necropsy Findings for Offspring 

Group: 4 Dose Level: 750 mg/kg bw/day 

Litter Number 

85 

86 

87 NP 

88 

89 

90 

91 

92 

93 

94 

95 

96 

Interim Deaths 

Necropsy Day (Post Offspring Sex & 

Partum) Number Macroscopic Observation Total Number 

of Offspring 

3M 7F 

6M 7F 

5M 6F 

9M 3F 

5M 13F 

4M 10F 

6M 6F 

5M BF 

9M 4F 

5M 6F 

BM 5F 

Page260 

Terminal kill 

~- Macroscopic Observation 

No abnormalities detected 

No abnormalities detected 

No abnormalities detected 

No abnormalities detected 

No abnormalities detected 

No abnormalities detected 

No abnormalities detected 

No abnormalities detected 

No abnormalities detected 

No abnormalities detected 

Small 
Harlan Study Number: 41205015 Report Page 261 

Appendix 12 Individual Necropsy Findings 

Group: 1 Dose Level: o (Control) Sex: Male 

Animal Death 

No. Mode Of Death Day (Week) Observation(s) 

SCHEDULED KILL 43 (7) No abnormalities detected 

2 SCHEDULED KILL 43 (7) No abnormalities detected 

3 SCHEDULED KILL 43 (7) Epididymides; Small 

Testes; Small 

Testes; Flaccid 

All remaining tissues had no abnormalities detected 

4 SCHEDULED KILL 43 (7) No abnormalities detected 

5 SCHEDULED KILL 43 (7) Lungs (With Bronchi); Reddened 

All remaining tissues had no abnormalities detected 

6 SCHEDULED KILL 43 (7) No abnormalities detected 

7 SCHEDULED KILL 43 (7) No abnormalities detected 

8 SCHEDULED KILL 43 (7) No abnormalities detected 

9 SCHEDULED KILL 43 (7) No abnormalities detected 

10 SCHEDULED KILL 43 (7) No abnormalities detected 

11 SCHEDULED KILL 43 (7) No abnormalities detected 

12 SCHEDULED KILL 43 (7) No abnormalities detected 
Harlan Study Number: 41205015 Report Page262 

Appendix 12 ( continued) Individual Necropsy Findings 

Group: 1 Dose Level: O (Control) Sex: Female 

Animal Death 

No. Mode Of Death Day (Week) Observation(s) 

13 SCHEDULED KILL 43 (7) No abnormalities detected 

14 SCHEDULED KILL 43 (7) No abnormalities detected 

15 SCHEDULED KILL 43 (7) No abnormalities detected 

16 SCHEDULED KILL 45 (7) No abnormalities detected 

17 SCHEDULED KILL 42 (6) No abnormalities detected 

18 SCHEDULED KILL 45 (7) No abnormalities detected 

19 SCHEDULED KILL 45 (7) No abnormalities detected 

20 SCHEDULED KILL 42 (6) No abnormalities detected 

21 SCHEDULED KILL 43 (7) No abnormalities detected 

22 SCHEDULED KILL 44 (7) No abnormalities detected 

23 SCHEDULED KILL 44 (7) No abnormalities detected 

24 SCHEDULED KILL 45 (7) No abnormalities detected 
Harlan Study Number: 41205015 Report Page 263 

Appendix 12 ( continued) Individual Necropsy Findings 

Group: 2 Dose Level: 50 mg/kg bw/day Sex: Male 

Animal Death 

No. Mode Of Death Day (Week) Observation(s) 

25 SCHEDULED KILL 43 (7) No abnormalities detected 

26 SCHEDULED KILL 43 (7) No abnormalities detected 

27 SCHEDULED KILL 43 (7) Lungs (With Bronchi); median lobe; Mass: Fibrous mass 7mm x 7mm x7mm. 

All remaining tissues had no abnormalities detected 

28 SCHEDULED KILL 43 (7) No abnormalities detected 

29 SCHEDULED KILL 43 (7) Epididymides; Small 

Testes; Small 

Testes; Flaccid 

All remaining tissues had no abnormalities detected 

30 SCHEDULED KILL 43 (7) No abnormalities detected 

31 SCHEDULED KILL 43 (7) No abnormalities detected 

32 SCHEDULED KILL 43 (7) No abnormalities detected 

33 SCHEDULED KILL 43 (7) No abnormalities detected 

34 SCHEDULED KILL 43 (7) No abnormalities detected 

35 SCHEDULED KILL 43 (7) No abnormalities detected 

36 SCHEDULED KILL 43 (7) No abnormalities detected 
Harlan Study Number: 41205015 Report Page264 

Appendix 12 ( continued) Individual Necropsy Findings 

Group: 2 Dose Level: 50 mg/kg bw/day Sex: Female 

Animal Death 

No. Mode Of Death Day (Week) Observation(s) 

37 SCHEDULED KILL 44 (7) Kidneys; Increased Pelvic Space All remaining tissues had no abnormalities detected 

38 SCHEDULED KILL 45 (7) No abnormalities detected 

39 SCHEDULED KILL 43 (7) No abnormalities detected 

40 SCHEDULED KILL 43 (7) No abnormalities detected 

41 SCHEDULED KILL 42 (6) No abnormalities detected 

42 SCHEDULED KILL 42 (6) No abnormalities detected 

43 SCHEDULED KILL 45 (7) No abnormalities detected 

44 SCHEDULED KILL 45 (7) No abnormalities detected 

45 SCHEDULED KILL 43 (7) No abnormalities detected 

46 SCHEDULED KILL 43 (7) No abnormalities detected 

47 SCHEDULED KILL 44 (7) No abnormalities detected 

48 SCHEDULED KILL 44 (7) No abnormalities detected 
Harlan Study Number: 41205015 Report Page 265 

Appendix 12 ( continued) Individual Necropsy Findings 

Group: 3 Dose Level: 250 mg/kg bw/day Sex: Male 

Animal Death 

No. Mode Of Death Day (Week) Observation(s) 

49 SCHEDULED KILL 43 (7) No abnormalities detected 

50 SCHEDULED KILL 43 (7) No abnormalities detected 

51 SCHEDULED KILL 43 (7) No abnormalities detected 

52 SCHEDULED KILL 43 (7) No abnormalities detected 

53 SCHEDULED KILL 43 (7) No abnormalities detected 

54 SCHEDULED KILL 43 (7) No abnormalities detected 

55 SCHEDULED KILL 43 (7) No abnormalities detected 

56 SCHEDULED KILL 43 (7) Kidneys; left; Increased Pelvic Space Kidneys; left; Fluid Filled 

All remaining tissues had no abnormalities detected 

57 SCHEDULED KILL 43 (7) No abnormalities detected 

58 SCHEDULED KILL 43 (7) No abnormalities detected 

59 SCHEDULED KILL 43 (7) No abnormalities detected 

60 SCHEDULED KILL 43 (7) No abnormalities detected 
Harlan Study Number: 41205015 Report Page 266 

Appendix 12 ( continued) Individual Necropsy Findings 

Group: 3 Dose Level: 250 mg/kg bw/day Sex: Female 

Animal Death 

No. Mode Of Death Day (Week) Observation(s) 

61 SCHEDULED KILL 44 (7) No abnormalities detected 

62 SCHEDULED KILL 46 (7) No abnormalities detected 

63 SCHEDULED KILL 43 (7) No abnormalities detected 

64 SCHEDULED KILL 44 (7) No abnormalities detected 

65 SCHEDULED KILL 44 (7) No abnormalities detected 

66 SCHEDULED KILL 42 (6) No abnormalities detected 

67 SCHEDULED KILL 45 (7) No abnormalities detected 

68 SCHEDULED KILL 42 (6) No abnormalities detected 

69 SCHEDULED KILL 44 (7) No abnormalities detected 

70 SCHEDULED KILL 43 (7) No abnormalities detected 

71 SCHEDULED KILL 44 (7) No abnormalities detected 

72 SCHEDULED KILL 46 (7) No abnormalities detected 
Harlan Study Number: 41205015 Report Page267 

Appendix 12 ( continued) Individual Necropsy Findings 

Group: 4 Dose Level: 750 mg/kg bw/day Sex: Male 

Animal Death 

No. Mode Of Death Day (Week) Observation(s) 

73 SCHEDULED KILL 43 (7) No abnormalities detected 

74 SCHEDULED KILL 43 (7) No abnormalities detected 

75 SCHEDULED KILL 43 (7) No abnormalities detected 

76 SCHEDULED KILL 43 (7) No abnormalities detected 

77 SCHEDULED KILL 43 (7) No abnormalities detected 

78 SCHEDULED KILL 43 (7) No abnormalities detected 

79 SCHEDULED KILL 43 (7) No abnormalities detected 

80 SCHEDULED KILL 43 (7) No abnormalities detected 

81 SCHEDULED KILL 43 (7) No abnormalities detected 

82 SCHEDULED KILL 43 (7) No abnormalities detected 

83 SCHEDULED KILL 43 (7) No abnormalities detected 

84 SCHEDULED KILL 43 (7) No abnormalities detected 
Harlan Study Number: 41205015 Report Page 268 

Appendix 12 ( continued) Individual Necropsy Findings 

Group: 4 Dose Level: 750 mg/kg bw/day Sex: Female 

Animal Death 

No. Mode Of Death Day (Week) Observation(s) 

85 SCHEDULED KILL 42 (6) No abnormalities detected 

86 SCHEDULED KILL 44 (7) No abnormalities detected 

87 SCHEDULED KILL 42 (6) Lungs (With Bronchi); Reddened 

All remaining tissues had no abnormalities detected 

88 SCHEDULED KILL 42 (6) No abnormalities detected 

89 SCHEDULED KILL 43 (7) No abnormalities detected 

90 SCHEDULED KILL 54 (8) No abnormalities detected 

91 SCHEDULED KILL 44 (7) No abnormalities detected 

92 SCHEDULED KILL 42 (6) No abnormalities detected 

93 SCHEDULED KILL 53 (8) No abnormalities detected 

94 SCHEDULED KILL 42 (6) No abnormalities detected 

95 SCHEDULED KILL 45 (7) No abnormalities detected 

96 SCHEDULED KILL 43 (7) No abnormalities detected 
Harlan Study Number: 41205015 Report Page 269 

Appendix 13 Individual and Group Mean Organ Weights 

Group Animal Epididy- Seminal 

(Sex) Number Day Adrenals Brain mid es Heart Kidneys Liver Pituitary Prostate vesicles Spleen Testes Thymus Thyroid 

Number g g g g g g g g g g g g g 

1 (M) 1 43 0.0736 2.1443 1 .4940 1 .2439 2.3877 12 .1858 0.0100 0.5812 2.8611 0.6730 3.8686 0.3656 0.0276 --- ---

2 43 0.0680 1.9421 1 .5261 0.9843 2.2134 12.0389 0.0102 0.5557 2.5679 0.6864 3.3255 0.4154 0.0241 - -- ---

3 43 0 .1279 2.0185 1 .2462 1 .1672 2 .1771 12.1619 0.0136 0.4816 1 .9744 0.7279 1 . 4766 0.3658 0.0244 - --

4 43 0.0809 1.9138 1 .1778 1 .1769 2.0426 11 .2170 0.0128 0.4564 1 .9959 0.7478 3.0325 0.3491 0.0173 - --

5 43 0.0754 2.0263 1 .5456 0.8496 2 .0681 12.3641 0.0113 0.5986 2.3326 0.7056 3.6573 0.4467 0.0212 - --

6 43 0.0705 2.0012 1 .5446 0.9900 2.2715 10.3368 0.0110 0.7359 2.4901 0.7093 3.4676 0.3074 0.0239 

7 43 0.0607 2.0341 1 .5998 1 .2737 2.4294 12.8814 0.0139 0.5442 2.3946 0.6227 4 .1127 0.4841 0.0243 - --

8 43 0.0771 2 .1103 1 . 3971 0.9357 1.9344 9.9041 0.0105 0.6238 2.7761 0.5463 3.9675 0.2342 0.0219 - --

9 43 0.0743 2. 1149 1 .6719 1.1991 2.5142 14.2513 0.0106 0.7472 2.2484 0.8426 3.9337 0.4929 0.0164 -

10 43 0.0777 1 .9897 1 .7239 1 .1464 2.2224 10.2537 0.0129 0.8584 2.2013 0.7152 3.7348 0.3806 0.0169 --

11 43 0.0802 2.0377 1 .6414 1 .1506 2.3054 12.3507 0.0118 0.6588 2.8309 0.8130 3.4745 0.4182 0.0315 --

12 43 0.0616 2.1334 1 .5274 0.8582 2.1964 10.3659 0.0116 0.6017 1 .9933 0.6981 3.6252 0.3914 0.0250 

Dose Levels: Group 1 - o (Control) Group 2 - 50 mg/kg bw/day Group 3 - 250 mg/kg bw/day Group 4 - 750 mg/kg bw/day 
Harlan Study Number: 41205015 Report Page 270 

Appendix 13 ( continued) Individual and Group Mean Organ Weights 

Group Animal Epididy- Seminal 

(Sex) Number Day Adrenals Brain mid es Heart Kidneys Liver Pituitary Prostate vesicles Spleen Testes Thymus Thyroid 

Number g g g g g g g g g g g g g 

2(M) 25 43 0.0875 2.0035 1.8649 1.1475 2.3813 12.9192 0.0145 0.7236 2.2860 0.7231 3.6791 0.2826 0.0242 --- -- --- 26 43 0.0757 2.0694 1 .4551 0.9043 2.4173 12.2344 0.0124 0.4008 2.1948 0.7079 3.5921 0.3787 0.0196 - --- 27 43 0.0628 1.8753 1.2123 1 .1013 2.1266 11 .4197 0.0142 0.6806 2.2072 0.7285 3.2621 0.3196 0.0395 

- -- 28 43 0.0615 1. 7988 1.2107 0.9803 1 .9301 10.9231 0.0086 0.4876 1 .9801 0.5820 3.0692 0.2827 0.0275 - --

29 43 0.0674 2.0119 0.8928 0.9939 2.3214 13.1545 0.0150 0.4764 2 .1718 0.9492 1.4548 0.4512 0.0296 - --

30 43 0.0955 2.2611 1 .6604 1 . 3158 2.0938 12.2628 0.0104 0.5563 1 .1491 0.7522 3.8503 0.5966 0.0330 - --

31 43 0.0803 1 .9452 1 .4068 0.9876 2.2339 12.1215 0.0140 0.5618 2.0187 0.6332 3.5725 0.3464 0.0234 - --

32 43 0.0789 2 .1016 1 .5483 1.3879 2.5332 12.4895 0.0137 0.8106 2.5730 0.7481 3.9314 0.4924 0.0341 - --

33 43 0.0798 2.1508 1 .5558 0.9680 2.4574 11.3828 0.0126 0.7192 3.1667 0.7188 3.7988 0.2083 0.0232 - --

34 43 0.0672 2 .1281 1 .6618 1 . 1171 2.2860 12.9702 0.0156 0.6383 2.8861 0.9066 4.2510 0.3923 0.0308 - --

35 43 0.0761 2.2631 1 .4487 1.0494 2.3848 12.1641 0.0123 0.6549 2.6317 0.8614 3.7279 0.2401 0.0338 - --

36 43 0.0945 2.0333 1 .4904 1.1287 2.3065 11.0239 0.0120 0.5692 2.6081 0.6316 3.4233 0.4037 0.0299 

Dose Levels: Group 1 - o (Control) Group 2 - 50 mg/kg bw/day Group 3 - 250 mg/kg bw/day Group 4 - 750 mg/kg bw/day 
Harlan Study Number: 41205015 Report Page 271 

Appendix 13 ( continued) Individual and Group Mean Organ Weights 

Group Animal Epididy- Seminal 

(Sex) Number Day Adrenals Brain mides Heart Kidneys Liver Pituitary Prostate vesicles Spleen Testes Thymus Thyroid 

Number g g g g g g g g g g g g g 

3(M) 49 43 0.0775 2 .1013 1.4179 1.1313 2.2968 11.3304 0.0114 0.7106 2.7581 0.7223 3.7224 0.5021 0.0247 --- --

50 43 0.0824 1.9016 1 .4986 1.0498 2.2243 11.0820 0.0102 0.4866 2.5935 0.7424 3.3671 0.3302 0.0253 - --

51 43 0.0795 2.0461 1 .5288 0.8636 2.4806 12.1867 0.0138 0.5073 2.5646 0.7185 3.4557 0.3434 0.0220 - -- --- 52 43 0.0806 1. 9861 1. 7080 1.3436 2. 5481 12.6608 0.0136 0.6591 2.5520 0.7565 4.0138 0.4224 0.0251 - --

53 43 0.0910 2.0995 1 .8133 1 .1728 2.4602 12.4525 0.0117 0.7811 2.0150 0.7713 4.3082 0.6322 0.0218 - --

54 43 0.0723 2.0355 1 .4961 1 .1566 2.3709 11.8185 0.0118 0.5946 2.3869 0.8240 3.8903 0.3544 0.0278 

- -- 55 43 0.0689 2.0504 1. 7580 1 .1284 2.3975 12.4809 0.0122 0.6569 2.4268 0.6961 4.1806 0.2860 0.0206 

- -- 56 43 0.0656 1 .9370 1 .4497 0.9519 2.4370 9.8506 0.0124 0.5523 2.2490 0.7230 3.6106 0.4463 0.0280 - --

57 43 0.0658 1.9630 1 .3793 0.9529 2 .1449 11.3742 0.0108 0.4605 1.9256 0.6806 3.2586 0.5183 0.0275 

- -- 58 43 0.0700 2.0068 1 .3669 0.9975 2.2084 12.3900 0.0116 0.4742 1 .8138 0.7538 3.2351 0.3914 0.0240 - -- -- 59 43 0.0716 2.0851 1 .4760 1.1567 2.2838 10.3656 0.0097 0.5056 1.9690 0.6905 3.7863 0.4933 0.0214 - --

60 43 0.0925 1.8664 1 .5854 1 .0741 2.2777 11 .1209 0.0122 0.5275 2.4804 0.7126 3.2182 0.3909 0.0188 

Dose Levels: Group 1 - O (Control) Group 2 - 50 mg/kg bw/day Group 3 - 250 mg/kg bw/day Group 4 - 750 mg/kg bw/day 
Harlan Study Number: 41205015 Report Page 272 

Appendix 13 ( continued) Individual and Group Mean Organ Weights 

Group Animal Epididy- Seminal 

(Sex) Number Day Adrenals Brain mid es Heart Kidneys Liver Pituitary Prostate vesicles Spleen Testes Thymus Thyroid 

Number g g g g g g g g g g g g g 

4(M) 73 43 0.0790 2.0810 1 .4803 1 .0887 2 .1537 11.2632 0.0126 0.5446 2 .1671 0.5809 3.7906 0.3159 0.0210 --- -- ---

74 43 0.0713 2.0526 1 .4434 0.9612 2.2329 11 .8855 0.0100 0.5525 1 .7961 0.6862 3.4164 0.2740 0.0183 

75 43 0.0767 2.0701 1 . 5631 1.0837 2.2347 12.0591 0.0130 0.4875 1.8697 0.7670 3.9498 0.5553 0.0399 - - 76 43 0. 1018 2.0086 1.8102 1.2994 2.3852 12 .1008 0.0108 0.6022 1 .5484 0.8051 3.9440 0.3996 0.0196 - -- ---

77 43 0.0591 1 . 9513 1 .5445 1 .0396 2 .1592 12.0304 0.0123 0.5242 1 .9308 0.7378 4.2019 0.4769 0.0285 - --

78 43 0.0875 2.0697 1 .5487 1. 0271 2.4757 13.0204 0.0135 0.6825 2.3596 2.3572 3.7466 0.3713 0.0283 - --

79 43 0.0724 1.8640 1 .3790 0.9453 2.2822 12.1129 0.0108 0.5590 1 .9389 0.5743 3 .1607 0.4654 0.0224 - --

80 43 0.0760 2 .1132 1 .5510 1 . 0891 2.4096 12.4719 0.0136 0.5918 1 .8694 0.7304 3.5134 0.3391 0.0277 - --

81 43 0.0894 2.1994 1 .6582 1.0834 2.4868 12.7299 0.0100 0.7308 2.1337 0.8089 3.7753 0.2840 0.0429 --

82 43 0.0604 2.0721 1 .4407 1 .0953 2.1053 11 .1856 0.0084 0.5520 1 .8294 0.6321 3.8489 0.4420 0.0251 - 83 43 0.0801 2.1304 1.7593 1 . 1107 2. 3421 12 .1240 0.0109 0.5144 2.0534 0.6537 4.3291 0.4838 0.0309 - --

84 43 0.0806 1 .9730 1 .4229 1 . 0541 2. 1621 12 .1255 0.0097 0.5514 2 .1653 0.6628 3.7596 0.3764 0.0366 

Dose Levels: Group 1 - o (Control) Group 2 - 50 mg/kg bw/day Group 3 - 250 mg/kg bw/day Group 4 - 750 mg/kg bw/day 
Harlan Study Number: 41205015 Report Page 273 

Appendix 13 ( continued) Individual and Group Mean Organ Weights 

Group Animal 

(Sex) Number Day Adrenals Brain Heart Kidneys Liver Ovaries Pituitary Spleen Thymus Thyroid 

Number g g g g g g g g g g 

1 ( F) 13 43 0.0809 2.0555 0.7697 1.5335 10.6504 0 .1152 0.0184 0.6798 0.2364 0.0237 --- -- --- 14 43 0.0773 1 .9568 0.8107 1.5453 8.9510 0.1224 0.0159 0.6148 0 .1536 0.0171 - -- --- 15 43 0.0917 1 .8494 0.9580 1 . 5819 7.7741 0.1070 0.0145 0.5441 0.4196 0.0200 - -- 16 45 0.0917 1 .9509 0.8166 1 .3770 10.1651 0 .1204 0.0178 0.6570 0.2858 0.0192 -

17 42 0.1147 1 .9588 0.9421 1.6107 10.6019 0 .1169 0.0185 0.5508 0.2709 0.0219 - -- --

18 45 0.0855 1. 7760 0.7262 1 . 7179 10.5511 0 .1276 0.0182 0.7322 0.1605 0.0254 - -- 19 45 0.0892 1 .9389 0.8107 1 .5598 11.0369 0.0946 0.0101 0.7796 0.3251 0.0234 -

20 42 0.0828 1 .9386 0.8647 1 .6030 10.1411 0.1280 0.0147 0.5497 0.2796 0.0229 - -- --- 21 43 0.0987 1 . 7419 0.6424 1 .4842 9.0193 0.1224 0.0136 0.7061 0 .1652 0.0225 -

22 44 0.0896 1 .7925 0.8887 1 .5797 10 .1758 0 .1140 0.0180 0.6451 0.2663 0.0284 -- 23 44 0 .1005 1 .9213 0.8364 1 .4839 11.4961 0 .1159 0.0152 0.6646 0.2853 0.0270 - -- 24 45 0.0861 1.8841 0.6778 1 .6222 9.6888 0 .1120 0.0137 0.6945 0.1475 0.0243 

Dose Levels: Group 1 - o (Control) Group 2 - 50 mg/kg bw/day Group 3 - 250 mg/kg bw/day Group 4 - 750 mg/kg bw/day 
Harlan Study Number: 41205015 Report Page 274 

Appendix 13 ( continued) Individual and Group Mean Organ Weights 

Group Animal 

(Sex) Number Day Adrenals Brain Heart Kidneys Liver Ovaries Pituitary Spleen Thymus Thyroid 

Number g g g g g g g g g g 

2(F) 37 44 0.0811 1 .8942 0.8321 1. 6274 9.8862 0 .1002 0.0102 0.6684 0. 1671 0.0303 --- -- 38 45 0.0888 1 .8236 0.7249 1.6216 10.8586 0 .1195 0.0203 0. 7601 0.2095 0.0206 - -- --- 39 43 0.0786 1 . 8921 0.8054 1 . 6617 8.0144 0.1032 0.0159 0.6010 0.3652 0.0285 - -- 40 43 0 .1139 2.0114 0.8508 1 .5344 10 .1269 0 .1166 0.0196 0.7315 0.2883 0.0270 - -- -

41 42 0.0846 1 .9680 0.7620 1. 5162 9.5310 0.1567 0.0189 0.6237 0.3819 0.0253 

42 42 0.0708 1 . 8351 0.7871 1 .4458 9.3228 0 .1265 0.0178 0.5334 0 .1402 0.0330 -- 43 45 0.0898 1 .9324 0.8481 1 .6295 11.1036 0.1362 0.0185 0.7430 0.2272 0.0218 -- 44 45 0 .1076 1 .8565 0.8033 1. 8195 12.8538 0.1412 0.0172 0.9088 0.2971 0.0322 -- 45 43 0 .1090 1 .9647 0.9410 1. 7325 11.9074 0.1299 0.0190 0.5890 0.1942 0.0367 -- -- 46 43 0 .1010 1 .9435 0.8176 1 .6368 11.5265 0.1496 0.0220 0.5655 0.2457 0.0234 - -- 47 44 0.0639 1 .8582 1.0478 1.5509 7.6501 0.1307 0.0160 0.5144 0.4547 0.0313 -- 48 44 0. 1016 2.0029 0.9185 1. 5961 10.0023 0. 1101 0.0158 0.6631 0.1935 0.0268 

Dose Levels: Group 1 - o (Control) Group 2 - 50 mg/kg bw/day Group 3 - 250 mg/kg bw/day Group 4 - 750 mg/kg bw/day 
Harlan Study Number: 41205015 Report Page 275 

Appendix 13 ( continued) Individual and Group Mean Organ Weights 

Group Animal 

(Sex) Number Day Adrenals Brain Heart Kidneys Liver Ovaries Pituitary Spleen Thymus Thyroid 

Number g g g g g g g g g g 

3(F) 61 44 0.0724 1 .9707 O.BBB3 1.5420 10. 1 BB6 0.1112 0.0151 0.4744 0.2115 0.0255 --- -- 62 46 0.0954 2.0012 0.8774 1.8198 12.8351 0.1754 0.0182 0.7778 0.2634 0.0244 - 63 43 0.0713 1 .8697 0.7065 1 .4845 10.0909 0.0958 0.0127 0.5410 0.1888 0.0235 - -- 64 44 0.0886 2.0670 1 .0379 1 . 4951 10.9938 0 .1310 0.0175 0.7738 0 .1953 0.0140 - -- 65 44 0.0821 1 . 8721 0.8317 1.5518 10.2238 0.1048 0.0158 0.5543 0.2879 0.0202 - -- 66 42 0.0959 1. 7434 0.8787 1.5797 10.7115 0.1025 0.0168 0.6110 0.1524 0.0201 

--- 67 45 0 .1014 1 .9068 0.8142 1 .6682 12.5421 0 .1331 0.0163 0.6463 0.2934 0.0236 - -- 68 42 0.0702 1 . 7137 0.6481 1 .4049 9.7140 0.0844 0.0155 0.5067 0.1538 0.0199 - -- 69 44 0 .1256 1 .8532 0. 8521 1. 5179 11.5033 0 .1619 0.0150 0.6142 0 .1736 0.0177 -- 70 43 0.0809 1 . 8391 0.8074 1 .6746 9.9322 0 .1219 0.0192 0.4561 0.1890 0.0267 -- 71 44 0.0641 1 . 9166 0.8554 1. 7906 11.5848 0. 1271 0.0174 0.6719 0.3382 0.0177 - 72 46 0.0868 1 .9647 0.8569 1 . 6185 10.7423 0.1230 0.0165 0.6127 0.2083 0.0248 

Dose Levels: Group 1 - o (Control) Group 2 - 50 mg/kg bw/day Group 3 - 250 mg/kg bw/day Group 4 - 750 mg/kg bw/day 
Harlan Study Number: 41205015 Report Page 276 

Appendix 13 ( continued) Individual and Group Mean Organ Weights 

Group Animal 

(Sex) Number Day Adrenals Brain Heart Kidneys Liver Ovaries Pituitary Spleen Thymus Thyroid 

Number g g g g g g g g g g 

4(F) 85 42 0.0947 1. 7772 1 .0737 1. 7782 10.7660 0.1257 0.0153 0.7424 0.2118 0.0333 --- -- --- 86 44 0 .1062 1 . 8831 1 . 0311 1 .6272 12.5462 0.1533 0.0132 0.7066 0.3215 0.0221 - -- 87 42 0.0612 1 . 7941 0.6404 1.6171 8.0528 0.0910 0.0104 0.6126 0.3139 0.0208 - -- 88 42 0.0767 1. 7075 0.7134 1 .4525 10.4177 0.0987 0.0157 0.5508 0 .1843 0.0295 - -- 89 43 0.0981 1 .8277 0.7765 1 .4655 10.9969 0. 1191 0.0143 0.6402 0.2144 0.0288 - --- 90 54 0.0914 1. 7577 0.9646 1.5262 13.6323 0 .1275 0.0141 0.7798 0 .1693 0.0125 - -- 91 44 0.0826 1 .8669 0.9074 1 . 5716 12.7620 0.1307 0.0134 0.6291 0.3767 0.0250 - -- 92 42 0 .1038 1 .9405 0.9895 1 .6807 12.0545 0.1068 0.0169 0.6246 0.2641 0.0278 - -- 93 53 0.0839 1 .6978 0.9477 1 .6562 11 .2473 0.1116 0.0153 0.6922 0.1773 0.0136 -- 94 42 0.1029 1.8902 0.8126 1. 7963 12.3259 0.1366 0.0148 0.6667 0.2545 0.0312 - -- -- 95 45 0.0887 1 .9012 0.7628 1 .4633 10.2295 0.0921 0.0120 0.5413 0.2136 0.0195 - -- 96 43 0.0746 1 .8675 0.6853 1.5423 10.6476 0 .1190 0.0154 0.6650 0.1727 0.0356 

Dose Levels: Group 1 - O (Control) Group 2 - 50 mg/kg bw/day Group 3 - 250 mg/kg bw/day Group 4 - 750 mg/kg bw/day 
Harlan Study Number: 41205015 Report Page 277 

Appendix 14 Individual and Group Mean Relative Organ Weights 

Group Animal Relative Relative Relative Relative Relative Relative Relative 

(Sex) Number Day Bodywt Adrenals Brain Epididys Heart Kidneys Liver Pituitary Number g % % % % % % % 

1 (M) 1 43 391 0.0188 0.5484 0.3821 0.3181 0.6107 3 .1166 0.0026 --- -- 2 43 387 0.0176 0.5018 0.3943 0.2543 0.5719 3 .1108 0.0026 -- 3 43 385 0.0332 0.5243 0.3237 0.3032 0.5655 3 .1589 0.0035 

4 43 409 0.0198 0.4679 0.2880 0.2878 0.4994 2.7425 0.0031 - --- --- 5 43 406 0.0186 0.4991 0.3807 0.2093 0.5094 3.0453 0.0028 - -- --- 6 43 379 0.0186 0.5280 0.4075 0.2612 0.5993 2.7274 0.0029 

7 43 405 0.0150 0.5022 0.3950 0.3145 0.5999 3.1806 0.0034 --- 8 43 346 0.0223 0.6099 0.4038 0.2704 0.5591 2.8625 0.0030 - --- 9 43 417 0.0178 0.5072 0.4009 0.2876 0.6029 3.4176 0.0025 - -- --- 10 43 374 0.0208 0.5320 0.4609 0.3065 0.5942 2.7416 0.0034 - -- --- 11 43 410 0.0196 0.4970 0.4003 0.2806 0.5623 3.0124 0.0029 - --- 12 43 391 0.0158 0.5456 0.3906 0.2195 0.5617 2. 6511 0.0030 

Dose Levels: Group 1 - o (Control) Group 2 - 50 mg/kg bw/day Group 3 - 250 mg/kg bw/day Group 4 - 750 mg/kg bw/day 
Harlan Study Number: 41205015 Report Page 278 

Appendix 14 (continued) Individual and Group Mean Relative Organ Weights 

(continued) 

Group Animal Relative Relative Relative Relative Relative Relative 

(Sex) Number Day Prostate Sem.Ves. Spleen Testes Thymus Thyroid 

Number % % % % % % 

1 (M) 1 43 0.1486 0.7317 0 .1721 0.9894 0.0935 0.0071 --- -- 2 43 0 .1436 0.6635 0 .1774 0.8593 0.1073 0.0062 - -- 3 43 0 .1251 0.5128 0 .1891 0.3835 0.0950 0.0063 -

4 43 0.1116 0.4880 0 .1828 0.7414 0.0854 0.0042 - -- 5 43 0.1474 0.5745 0 .1738 0.9008 0 .1100 0.0052 -- -- 6 43 0 .1942 0.6570 0.1872 0.9149 0.0811 0.0063 - -- 7 43 0 .1344 0.5913 0 .1538 1 . 0155 0 .1195 0.0060 - -- 8 43 0 .1803 0.8023 0 .1579 1 .1467 0.0677 0.0063 - -- 9 43 0 .1792 0.5392 0.2021 0.9433 0.1182 0.0039 - -- 10 43 0.2295 0.5886 0 .1912 0.9986 0 .1018 0.0045 - -- 11 43 0 .1607 0.6905 0 .1983 0.8474 0.1020 0.0077 - -- 12 43 0 .1539 0.5098 0.1785 0.9272 0 .1001 0.0064 

Dose Levels: Group 1 - o (Control) Group 2 - 50 mg/kg bw/day Group 3 - 250 mg/kg bw/day Group 4 - 750 mg/kg bw/day 
Harlan Study Number: 41205015 Report Page 279 

Appendix 14 (continued) Individual and Group Mean Relative Organ Weights 

Group Animal Relative Relative Relative Relative Relative Relative Relative 

(Sex) Number Day Bodywt Adrenals Brain Epididys Heart Kidneys Liver Pituitary 

Number g % % % % % % % 

2(M) 25 43 389 0.0225 0.5150 0.4794 0.2950 0.6122 3.3211 0.0037 --- -- -- --- 26 43 403 0.0188 0.5135 0.3611 0.2244 0.5998 3.0358 0.0031 - -- -- 27 43 374 0.0168 0.5014 0.3241 0.2945 0.5686 3.0534 0.0038 - -- -- 28 43 349 0.0176 0.5154 0.3469 0.2809 0.5530 3.1298 0.0025 - -- -- 29 43 417 0.0162 0.4825 0.2141 0.2383 0.5567 3.1546 0.0036 - -- -- 30 43 393 0.0243 0.5753 0.4225 0.3348 0.5328 3.1203 0.0026 - -- -- 31 43 358 0.0224 0.5434 0.3930 0.2759 0.6240 3.3859 0.0039 - -- -- 32 43 414 0.0191 0.5076 0.3740 0.3352 0.6119 3.0168 0.0033 - -- -- 33 43 390 0.0205 0.5515 0.3989 0.2482 0.6301 2.9187 0.0032 

- -- -- -- 34 43 404 0.0166 0.5268 0.4113 0.2765 0.5658 3.2104 0.0039 - -- -- 35 43 383 0.0199 0.5909 0.3783 0.2740 0.6227 3.1760 0.0032 - -- -- 36 43 371 0.0255 0.5481 0.4017 0.3042 0.6217 2.9714 0.0032 

Dose Levels: Group 1 - o (Control) Group 2 - 50 mg/kg bw/day Group 3 - 250 mg/kg bw/day Group 4 - 750 mg/kg bw/day 
Harlan Study Number: 41205015 Report Page 280 

Appendix 14 (continued) Individual and Group Mean Relative Organ Weights 

(continued) 

Group Animal Relative Relative Relative Relative Relative Relative 

(Sex) Number Day Prostate Sem.Ves. Spleen Testes Thymus Thyroid Number % % % % % % 

2(M) 25 43 0 .1860 0.5877 0 .1859 0.9458 0.0726 0.0062 --- -- 26 43 0.0995 0.5446 0 .1757 0.8913 0.0940 0.0049 - -- 27 43 0 .1820 0.5902 0 .1948 0.8722 0.0855 0.0106 - -- 28 43 0 .1397 0.5674 0 .1668 0.8794 0.0810 0.0079 - -- - 29 43 0 .1142 0.5208 0.2276 0.3489 0.1082 0.0071 - -- --- 30 43 0.1416 0.2924 0 .1914 0.9797 0 .1518 0.0084 -

31 43 0 .1569 0.5639 0 .1769 0.9979 0.0968 0.0065 - -- 32 43 0 .1958 0.6215 0 .1807 0.9496 0 .1189 0.0082 - -- 33 43 0.1844 0.8120 0 .1843 0.9741 0.0534 0.0059 -

34 43 0.1580 0.7144 0.2244 1 .0522 0.0971 0.0076 - -- 35 43 0 .1710 0.6871 0.2249 0.9733 0.0627 0.0088 - -- 36 43 0 .1534 0.7030 0 .1702 0.9227 0.1088 0.0081 

Dose Levels: Group 1 - o (Control) Group 2 - 50 mg/kg bw/day Group 3 - 250 mg/kg bw/day Group 4 - 750 mg/kg bw/day 
Harlan Study Number: 41205015 Report Page 281 

Appendix 14 (continued) Individual and Group Mean Relative Organ Weights 

Group Animal Relative Relative Relative Relative Relative Relative Relative 

(Sex) Number Day Bodywt Adrenals Brain Epididys Heart Kidneys Liver Pituitary 

Number g % % % % % % % 

3(M) 49 43 348 0.0223 0.6038 0.4074 0.3251 0.6600 3.2559 0.0033 --- --- 50 43 387 0.0213 0.4914 0.3872 0.2713 0.5748 2.8636 0.0026 -- --- --- 51 43 393 0.0202 0.5206 0.3890 0.2197 0.6312 3.1009 0.0035 - -- --- 52 43 440 0.0183 0.4514 0.3882 0.3054 0.5791 2.8775 0.0031 - -- --- 53 43 424 0.0215 0.4952 0.4277 0.2766 0.5802 2.9369 0.0028 -- --- --- 54 43 384 0.0188 0 .5301 0.3896 0.3012 0.6174 3.0777 0.0031 - --- 55 43 386 0.0178 0.5312 0.4554 0.2923 0. 6211 3.2334 0.0032 - -- ---

56 43 389 0.0169 0.4979 0.3727 0.2447 0.6265 2.5323 0.0032 - -- --- 57 43 382 0.0172 0.5139 0.3611 0.2495 0.5615 2.9775 0.0028 - -- --- --- 58 43 357 0.0196 0.5621 0.3829 0.2794 0.6186 3.4706 0.0032 - -- --- 59 43 378 0.0189 0.5516 0.3905 0.3060 0.6042 2.7422 0.0026 - -- --- 60 43 408 0.0227 0.4575 0.3886 0.2633 0.5583 2.7257 0.0030 

Dose Levels: Group 1 - o (Control) Group 2 - 50 mg/kg bw/day Group 3 - 250 mg/kg bw/day Group 4 - 750 mg/kg bw/day 
Harlan Study Number: 41205015 Report Page282 

Appendix 14 (continued) Individual and Group Mean Relative Organ Weights 

(continued) 

Group Animal Relative Relative Relative Relative Relative Relative 

(Sex) Number Day Prostate Sem.Ves. Spleen Testes Thymus Thyroid 

Number % % % % % % 

3(M) 49 43 0.2042 0.7926 0.2076 1 .0697 0. 1443 0.0071 -- -- 50 43 0. 1257 0.6702 0. 1918 0 .8701 0.0853 0.0065 

- -- 51 43 0. 1291 0.6526 0. 1828 0.8793 0.0874 0.0056 

- -- 52 43 0. 1498 0.5800 0. 1719 0.9122 0.0960 0.0057 - -- 53 43 0. 1842 0.4752 0. 1819 1 . 0161 0. 1491 0.0051 

- -- 54 43 0. 1548 0.6216 0.2146 1 . 0131 0.0923 0.0072 

- -- 55 43 0. 1702 0.6287 0. 1803 1. 0831 0.0741 0.0053 

- -- 56 43 0. 1420 0.5781 0. 1859 0.9282 0.1147 0.0072 - -- 57 43 0. 1205 0.5041 0. 1782 0.8530 0. 1357 0.0072 - -- --- 58 43 0. 1328 0.5081 0.2111 0.9062 0. 1096 0.0067 

- -- 59 43 0. 1338 0.5209 0. 1827 1 .0017 0. 1305 0.0057 

- -- 60 43 0. 1293 0.6079 0.1747 0.7888 0.0958 0.0046 

Dose Levels: Group 1 - o (Control) Group 2 - 50 mg/kg bw/day Group 3 - 250 mg/kg bw/day Group 4 - 750 mg/kg bw/day 
Harlan Study Number: 41205015 Report Page 283 

Appendix 14 (continued) Individual and Group Mean Relative Organ Weights 

Group Animal Relative Relative Relative Relative Relative Relative Relative 

(Sex) Number Day Bodywt Adrenals Brain Epididys Heart Kidneys Liver Pituitary Number g % % % % % % % 

4(M) 73 43 368 0.0215 0.5655 0.4023 0.2958 0.5852 3.0607 0.0034 --- -- --- --- 74 43 365 0.0195 0.5624 0.3955 0.2633 0.6118 3.2563 0.0027 - --- --- 75 43 383 0.0200 0.5405 0.4081 0.2830 0.5835 3 .1486 0.0034 

- -- --- 76 43 366 0.0278 C>".5488 0.4946 0.3550 0.6517 3.3062 0.0030 - -- --- 77 43 394 0.0150 0.4953 0.3920 0.2639 0.5480 3.0534 0.0031 - -- --- 78 43 401 0.0218 0.5161 0.3862 0.2561 0.6174 3.2470 0.0034 - -- --- 79 43 370 0.0196 0.5038 0.3727 0.2555 0.6168 3.2738 0.0029 - -- --- --- 80 43 401 0.0190 0.5270 0.3868 0.2716 0.6009 3 .1102 0.0034 - -- --- 81 43 370 0.0242 0.5944 0.4482 0.2928 0.6721 3.4405 0.0027 - -- --- --- 82 43 349 0.0173 0.5937 0.4128 0.3138 0.6032 3.2050 0.0024 

- -- --- ---

83 43 374 0.0214 0.5696 0.4704 0.2970 0.6262 3.2417 0.0029 

- -- --- 84 43 386 0.0209 0.5111 0.3686 0.2731 0.5601 3.1413 0.0025 

Dose Levels: Group 1 - o (Control) Group 2 - 50 mg/kg bw/day Group 3 - 250 mg/kg bw/day Group 4 - 750 mg/kg bw/day 
Harlan Study Number: 41205015 Report Page 284 

Appendix 14 (continued) Individual and Group Mean Relative Organ Weights 

(continued) 

Group Animal Relative Relative Relative Relative Relative Relative 

(Sex) Number Day Prostate Sem.Ves. Spleen Testes Thymus Thyroid 

Number % % % % % % 

4(M) 73 43 0 .1480 0.5889 0 .1579 1 . 0301 0.0858 0.0057 -- 74 43 0.1514 0.4921 0 .1880 0.9360 0.0751 0.0050 - -- 75 43 0 .1273 0.4882 0.2003 1 .0313 0.1450 0.0104 -- 76 43 0 .1645 0.4231 0.2200 1 .0776 0 .1092 0.0054 - -- 77 43 0 .1330 0.4901 0 .1873 1 .0665 0 .1210 0.0072 - -- --- 78 43 0 .1702 0.5884 0.5878 0.9343 0.0926 0.0071 - -- 79 43 0.1511 0.5240 0 .1552 0.8542 0.1258 0 .0061 - -- 80 43 0.1476 0.4662 0 .1821 0.8762 0.0846 0.0069 - -- 81 43 0 .1975 0.5767 0.2186 1 .0204 0.0768 0.0116 -

82 43 0 .1582 0.5242 0.1811 1 .1028 0.1266 0.0072 - -- 83 43 0.1375 0.5490 0 .1748 1 .1575 0 .1294 0.0083 - 84 43 0 .1428 0.5610 0 .1717 0.9740 0.0975 0.0095 

Dose Levels: Group 1 - O (Control) Group 2 - 50 mg/kg bw/day Group 3 - 250 mg/kg bw/day Group 4 - 750 mg/kg bw/day 
Harlan Study Number: 41205015 Report Page 285 

Appendix 14 (continued) Individual and Group Mean Relative Organ Weights 

Group Animal Relative Relative Relative Relative Relative Relative Relative Relative Relative Relative 

(Sex) Number Day Bodywt Adrenals Brain Heart Kidneys Liver Ovaries Pituitary Spleen Thymus Thyroid 

Number g % % % % % % % % % % 

1 ( F) 13 43 259 0.0312 0.7936 0.2972 0.5921 4. 1121 0.0445 0.0071 0.2625 0.0913 0.0092 --- -- --- 14 43 247 0.0313 0.7922 0.3282 0.6256 3.6239 0.0496 0.0064 0.2489 0.0622 0.0069 - -- --- 15 43 238 0.0385 0.7771 0.4025 0.6647 3.2664 0.0450 0.0061 0.2286 0.1763 0.0084 - -- --- 16 45 267 0.0343 0.7307 0.3058 0.5157 3.8072 0.0451 0.0067 0.2461 0 .1070 0.0072 - --- 17 42 257 0.0446 0.7622 0.3666 0.6267 4.1253 0.0455 0.0072 0.2143 0 .1054 0.0085 - -- --- 18 45 288 0.0297 0.6167 0.2522 0.5965 3.6636 0.0443 0.0063 0.2542 0.0557 0.0088 -- --- 19 45 272 0.0328 0.7128 0.2981 0.5735 4.0577 0.0348 0.0037 0.2866 0 .1195 0.0086 - --- --- 20 42 271 0.0306 0.7154 0.3191 0.5915 3.7421 0.0472 0.0054 0.2028 0.1032 0.0085 - -- --- 21 43 254 0.0389 0.6858 0.2529 0.5843 3.5509 0.0482 0.0054 0.2780 0.0650 0.0089 - -- --- --- 22 44 270 0.0332 0.6639 0.3291 0.5851 3.7688 0.0422 0.0067 0.2389 0.0986 0.0105 - -- --- 23 44 254 0.0396 0.7564 0.3293 0.5842 4.5260 0.0456 0.0060 0.2617 0 .1123 0.0106 - -- ---

24 45 243 0.0354 0.7753 0.2789 0.6676 3.9872 0.0461 0.0056 0.2858 0.0607 0.0100 

Dose Levels: Group 1 - O (Control) Group 2 - 50 mg/kg bw/day Group 3 - 250 mg/kg bw/day Group 4 - 750 mg/kg bw/day 
Harlan Study Number: 41205015 Report Page 286 

Appendix 14 (continued) Individual and Group Mean Relative Organ Weights 

Group Animal Relative Relative Relative Relative Relative Relative Relative Relative Relative Relative 

(Sex) Number Day Bodywt Adrenals Brain Heart Kidneys Liver Ovaries Pituitary Spleen Thymus Thyroid 

Number g % % % % % % % % % % 

2(F) 37 44 259 0.0313 0.7314 0.3213 0.6283 3.8171 0.0387 0.0039 0.2581 0.0645 0.0117 --- -- --- 38 45 270 0.0329 0.6754 0.2685 0.6006 4.0217 0.0443 0.0075 0.2815 0.0776 0.0076 - -- --- 39 43 246 0.0320 0.7691 0.3274 0.6755 3.2579 0.0420 0.0065 0.2443 0 .1485 0.0116 - -- --- 40 43 261 0.0436 0.7707 0.3260 0.5879 3.8800 0.0447 0.0075 0.2803 0 .1105 0.0103 - -- --- --- 41 42 251 0.0337 0.7841 0.3036 0.6041 3.7972 0.0624 0.0075 0.2485 0 .1522 0.0101 - --

42 42 232 0.0305 0.7910 0.3393 0.6232 4.0184 0.0545 0.0077 0.2299 0.0604 0.0142 - -- --- -- 43 45 269 0.0334 0.7184 0.3153 0.6058 4.1277 0.0506 0.0069 0.2762 0.0845 0.0081 -- --- --- 44 45 310 0.0347 0.5989 0.2591 0.5869 4.1464 0.0455 0.0055 0.2932 0.0958 0.0104 - -- --- 45 43 296 0.0368 0.6637 0.3179 0.5853 4.0228 0.0439 0.0064 0 .1990 0.0656 0.0124 -- --- 46 43 280 0.0361 0.6941 0.2920 0.5846 4 .1166 0.0534 0.0079 0.2020 0.0878 0.0084 - -- ---

47 44 243 0.0263 0.7647 0.4312 0.6382 3 .1482 0.0538 0.0066 0.2117 0 .1871 0.0129 - -- --- 48 44 258 0.0394 0.7763 0.3560 0.6186 3.8769 0.0427 0.0061 0.2570 0.0750 0.0104 

Dose Levels: Group 1 - o (Control) Group 2 - 50 mg/kg bw/day Group 3 - 250 mg/kg bw/day Group 4 - 750 mg/kg bw/day 
Harlan Study Number: 41205015 Report Page 287 

Appendix 14 (continued) Individual and Group Mean Relative Organ Weights 

Group Animal Relative Relative Relative Relative Relative Relative Relative Relative Relative Relative 

(Sex) Number Day Bodywt Adrenals Brain Heart Kidneys Liver Ovaries Pituitary Spleen Thymus Thyroid 

Number g % % % % % % % % % % 

3(F) 61 44 262 0.0276 0.7522 0.3390 0.5885 3.8888 0.0424 0.0058 0. 1811 0.0807 0.0097 --- -- --- -- 62 46 272 0.0351 0.7357 0.3226 0.6690 4.7188 0.0645 0.0067 0.2860 0.0968 0.0090 - -- --- -- 63 43 264 0.0270 0.7082 0.2676 0.5623 3.8223 0.0363 0.0048 0.2049 0.0715 0.0089 - -- ---

64 44 251 0.0353 0.8235 0.4135 0.5957 4.3800 0.0522 0.0070 0.3083 0.0778 0.0056 - -- --- 65 44 247 0.0332 0.7579 0.3367 0.6283 4 .1392 0.0424 0.0064 0.2244 0 .1166 0.0082 - -- --- 66 42 250 0.0384 0.6974 0.3515 0.6319 4.2846 0.0410 0.0067 0.2444 0.0610 0.0080 -- 67 45 285 0.0356 0.6691 0.2857 0.5853 4.4007 0.0467 0.0057 0.2268 0.1029 0.0083 - --- 68 42 250 0.0281 0.6855 0.2592 0.5620 3.8856 0.0338 0.0062 0.2027 0.0615 0.0080 - --- 69 44 250 0.0502 0.7413 0.3408 0.6072 4.6013 0.0648 0.0060 0.2457 0.0694 0.0071 - -- --- 70 43 264 0.0306 0.6966 0.3058 0.6343 3.7622 0.0462 0.0073 0.1728 0.0716 0.0101 - -- --- 71 44 287 0.0223 0.6678 0.2980 0.6239 4.0365 0.0443 0.0061 0.2341 0 .1178 0.0062 - -- --- -

72 46 270 0.0321 0.7277 0.3174 0.5994 3.9786 0.0456 0 .0061 0.2269 0. 0771 0.0092 

Dose Levels: Group 1 - O (Control) Group 2 - 50 mg/kg bw/day Group 3 - 250 mg/kg bw/day Group 4 - 750 mg/kg bw/day 
Harlan Study Number: 41205015 Report Page 288 

Appendix 14 (continued) Individual and Group Mean Relative Organ Weights 

Group Animal Relative Relative Relative Relative Relative Relative Relative Relative Relative Relative 

(Sex) Number Day Bodywt Adrenals Brain Heart Kidneys Liver Ovaries Pituitary Spleen Thymus Thyroid 

Number g % % % % % % % % % % 

4(F) 85 42 271 0.0349 0.6558 0.3962 0.6562 3.9727 0.0464 0.0056 0.2739 0.0782 0.0123 --- -- --- 86 44 279 0.0381 0.6749 0.3696 0.5832 4.4968 0.0549 0.0047 0.2533 0 .1152 0.0079 - --- 87 42 227 0.0270 0.7904 0.2821 0.7124 3.5475 0.0401 0.0046 0.2699 0.1383 0.0092 - -- --- 88 42 253 0.0303 0.6749 0.2820 0.5741 4.1177 0.0390 0.0062 0.2177 0.0728 0.0117 - -- --- 89 43 256 0.0383 0.7139 0.3033 0.5725 4.2957 0.0465 0.0056 0.2501 0.0838 0.0113 - -- --- 90 54 293 0.0312 0.5999 0.3292 0.5209 4.6527 0.0435 0.0048 0. 2661 0.0578 0.0043 -- ---

91 44 267 0.0309 0.6992 0.3399 0.5886 4.7798 0.0490 0.0050 0.2356 0.1411 0.0094 -- 92 42 270 0.0384 0.7187 0.3665 0.6225 4.4646 0.0396 0.0063 0.2313 0.0978 0.0103 - -- --- 93 53 274 0.0306 0.6196 0.3459 0.6045 4.1049 0.0407 0.0056 0.2526 0.0647 0.0050 --

94 42 284 0.0362 0.6656 0.2861 0.6325 4.3401 0.0481 0.0052 0.2348 0.0896 0.0110 - -- --- 95 45 239 0.0371 0.7955 0.3192 0.6123 4.2801 0.0385 0.0050 0.2265 0.0894 0.0082 - -- --- 96 43 261 0.0286 0.7155 0.2626 0.5909 4.0795 0.0456 0.0059 0.2548 0.0662 0.0136 

Dose Levels: Group 1 - O (Control) Group 2 - 50 mg/kg bw/day Group 3 - 250 mg/kg bw/day Group 4 - 750 mg/kg bw/day 
Harlan Study Number: 41205015 Report 

Appendix 15 Histopathology Phase Report 

PATHOLOGY PHASE REPORT 

Test Facility Study No.: 41215015 

Test Site Reference No.: 155-023 

Page 289 

PMDA H\:1>R.OL\:'ZED TO P~IA: ORAL (GAVAGE) COMBINED 

REPR.ODUCTIONJDE\"ELOPMEl\"TAL TOXICITY SCREL"«NG TEST IN THE RAT (OECD 421) 

P.M.Milar 

11115 
Harlan Study Number: 41205015 Report 

Appendix 15 ( continued) Histopathology Phase Report 

PATHOLOGY PHASE REPORT 

Test flllitDHy Study No.: 41205815 

Test She Reference No.: 155-W 

Page 290 

PMDA HYDROLYZED TO PMA: ORAL (GAV AGE) COMBINED 

REPRODUCTION/DEVELOPMENTAL TOXICITY SCREENING TEST IN THE RAT (OECD 4ll) 

GLPCOMPUANCESTATBMENT 

I. the undersigned. declare that this histopalhology repon contribution consdnnes a true record of the actions 

undertaken and die results obtained in the above stUdy. I accept re.spoulbility for die validity of the da!a am 

oontinn that this -,ect of the stud)I was conducted in compliance wilh Good Laboratory Practice (GLP) as 

required by the United Kingdom OLP Regulations 1999 (SI 1999 No. 3 l06) which are ht accordanc:e with the 

o,ganisation of Econmnic Co-operation and Deveklpment (OECD) Principles of Good Laboratory Practice 

(1982 and subsequent revisions). 

P.M.MIU.AR 8.V.M.S.,M.V .M .• M.R.C.V.S •• Dlplom1teA.C.V .P. 

{Principal Investigator - Histopathology) 

21115 
Harlan Study Number: 41205015 Report 

Appendix 15 (continued) Histopathology Phase Report 

PATHOLOGY PHASE REPORT 

Test FaelUty Study No.: 41285015 

THf Site Reftff1m1 No.: 155-023 

Page 291 

PMDA HYDROLYZED TO PMA: ORAL (GAVA~E) COMBINED 

REPRODUCTION/DEVELOPMENTAL TOXICITY SCREENING TEST IN THE RAT (OECD 421) 

QUALITY ASSURANCE STATEMENT 

I cm1nrm chat 1lliis repon gives an accume a«ollfll of 1bc methods used, alkl the rcponed results accurately 

reflect the ,aw data. 

The dates mt which various phases of lhe study wen: inspected and on which reports of these inspcclion.s were 

submitted 10 lhe pathorogist, were as follows: 

Date Inspected Dale Reported Date Reponed 

loPJ to Study Director 

Rel'iew of Study Plan& Amendmenl5 08103120EJ 08l03120l3 23!0812013 

Review of Study Docwnents 23/08l20.3 23J08/2013 U/0812013 

Rev ic,,v of Draft Report 23/08/2013 23/fl8/2013 231tl8f2013 

Review of Final Repon 23/08l2013 23/08/2013 23/08l2013 

Pn.:icess Md facility based inspections arc performed at regular incervaJs (every three monlhs and six monshs. 

n:spcctively) in compliance widl Standard Operating Procedure (SOP 8). The findings of those inspections and 

me responses of the Principal Jnvestigaklr (Test Site Management) are an:hivcd. The msa process-based 

inspection (slid&M':cadins:. slide labeling. receipt of materials, data transfer check) was carried out on I &h 

August 2013. 

The Study Di.ector wu advikd in a timely monnet of any signirlCIW findings f'or 1he wmt conducted at this 

·rest Sile dat misht have affeaed the OLP compliance of the study. 

~~ ...... ~~.t~l1~ 

JANE LAWRENCE B.Sc., Ph.D. (Quality Assurance Inspector) 

J/115 
Harlan Study Number: 41205015 Report 

Appendix 15 ( continued) Histopathology Phase Report 

Test Fadlby Smd.y Ne.41205015 

Test Sile RefRmft No.155-023 

PMDA. llydnlyzed to PMA.: Oral (Ga-ce) R.eprodndioa.lDevelopmeoml Ttnidty Screening Test in the 

Rat (OECD 421) 

CONTENTS 

SUMMARY&: CONCLUSION 

INTRODUcnON 

STUDY DESIGN 

MATERIALS 

METHODS 

RESULTS 

TABLES 

Table I 

Table2 

His1:opatboloay Smy IDcicleoce 

lndiulual Animal Pathology Findings 

5 

5 

6 

7 

8 

8 

10 

20 

41115 

Page292 
Harlan Study Number: 41205015 Report 

Appendix 15 ( continued) Histopathology Phase Report 

Test Fadluy Stwly No. 41205015 

Test Site Referace No. 155-823 

Pl-IDA hydrelyzed to Pt.IA: Oral (Gavage) Reprodudio11.IDevelopmental Toxicity Sn-eeoiag Test in tire 

Rat {OECD 421} 

SUMMARY & CONCLUSION 

The oral (gavage) adminismti.on of Pyromellitic dianb.ydride (PMDA hydmlyzed to PMA) to Han Wistar nts 

fur at least twenty-eight days at dosages of 50, 250 or 750 mg/kg bw/day produced no treatment-related 

!Justcpatboloeical fimtings. 

All of the :lmtlopathologicall fiodiings encountmed were considered to have arisen spontanecmslly or at post 

modem. 

INTRODUCTION 

Three groups of 12 male and 12 femaJe Hao Wistarrats were administered PMDA hydrolyzed to P.MA, by oral 

gavage, at dosages of 50, 250 or 750 mg/kg bw/day. Animals were treated, once daily, for up to eight weeks, 

starting fourteen days prior to pairing and comummg throughout the mating period. gestation and lactation. A 

similarly coostimkd group \V3S gi'Vell vebicl.e alone and served to pro,.>ide control data. At the end of the 

treatment period (Day 43 foe males and Day 5 post-partum for females) all the animals were euth.aniza:l 

hnmanely and subjected to a full necropsy exammatioa with special attention paid to the reproductive organs. 

The tisn.es of five males and .five females were processed and exami:nf.ld mstologically, in accordance with 

procedures laid down in the study pm aml amendments. 

This report contaim die. resu1ts of 1lbe pathologicaJI a.aminatiml of all animals as s,ecified in the study plan and 

amelldmeuts. 

51115 

Page 293 
Harlan Study Number: 41205015 

Appendix 15 ( continued) 

Test Fad&ly Study No. 41205815 

Test Site Reference No. ISS-Ol.l 

Report 

Histopathology Phase Report 

RIDA bydnlyzed to PMA: Oral (Gavage) ReprodudionlDevelopmeotal Tou:ity Saeeoiug Test in the 

Rat (OECD 411) 

STUDY DESIGN 

Experimental Deri,:n 

The dosage le,,els uedl and 1lhe mmmer of amm.als per group were as foDows: 

Group l l 3 4 

Dosa~ 0 50 250 750 

mglka bwlday 

M.ale Animal 1-12 25-36 49..(j() 73-84 Numbers 

Female Animal 13-24 37-48 61-72 85-96 Numbea 

The followme; bSS'lleS were ez.ammed from the first five lDilles of the contco] and highest dosage groups, and 

from the first five females in these gronps tu rear a &Im to Day 5 post-panum: 

All Gron Lesions, Adrentil Gla:11.ds, Bram (Cerebral & Cerebellllffl & Medulla/Pons), Caecum, Colon. 

Dttoda111m, Epiditfymides, Heart, llemn, Jejunum. Kidney'S, Liver • .Lun&s (+ Bronchi). Lymph Notks 

(Mandibular&: Mesmtenc), Manamary Gland, Owuies, Paradrpoid Gland, Prostate Gland, Pituitary Gland. 

Recmm, Sciatic Nerve, Seminal Vesicles (witll Coqulalil'l& Glands), Spinal Cmd (Cervical, Lumbar & 

17aarv.tctej, Spleen, Stomach, Te,stes, Tlaymm, Thyroid Glands, Trachea. Urmary Bladder, Uterus, Uterine 

Cenu. Vqma. 

~real eumination was also eanied oat mi 1lhe following tissues Imm the DITTP1ining mam study animals 

of the COEl'Ol and highr.st dosage groups, imemle males am al females that did not give birth: All Gross 

Lesi-.s, Epididymides, CoaguJamrg Glands. Mammary Gland, Ovaries, Pituitary Gland. Prostate Gland, 

Semmal Venf'les, Te.i:tes, lltena, Uterine Cenitt: and Vagina. 

61115 

Page 294