Document o962d4x9E4BK47N53jYDLK7n7

AR226-3198 TRADE SECRET Study Title H-24516: Subchronic Toxicity 90-Day Gavage Study in Rats with One-Generation Reproduction Evaluations Volume 2 of 5 Laboratory Project ID: DuPont-5386 TEST GUIDELINES: U.S. EPA Health Effects Test Guidelines OPPTS 870.3100 (1998) AUTHOR: Gregory S. Ladies, Ph.D., D.A.B.T. STUDY COMPLETED ON: December 3, 2001 PERFORMING LABORATORY: E.L du Font de Nemours and Company Haskell Laboratory for Toxicology and Industrial Medicine Elkton Road, P.O. Box 50 Newark, Delaware 19714-0050 WORK REQUEST NUMBER: yflHHIJ SERVICE CODE f NUMBER:! ffl\ SPONSOR STUDY NUMBER:lflHHHB \ Page 317 of 1500 ampany Sanitized. Does not eontahl TSCA CBI H-24516: Subchronic Toxicity 90-Day Gavage Study in Rats with One-Generation Reproduction Evaluations TABLE 44 MICROSCOPIC OBSERVATIONS IN MALE RATS LISTING INDIVIDUAL ANIMALS AFF NEOPLASTIC AND NON-NEOPLASTIC (90-DAY EXPOSURE EVALUATION INCLUDING EARLY DEATHS FROM THE REPRODUCTION LESIONS DIGESTIVE SYSTEM LIVER NO ABNORMALITY DETECTED NECROSIS, FOCAL. INFLAMMATION, SUBACUTE/CHRONIC. HYPERTROPHY, HEPATOCYTE, CENTRILOBULAR. TREATMENT (mg/kg/day) LESION INCID 0 25 I III (10) (10) 64327 643143 643150 643185 643189 643204 643205 643235 643241 643288 643300 64317 64317 64318 64322 64324 64326 64329 64329 64330 Figure in parentheses is number of animals microscopically examined for this tissue The absence of a number indicates the lesion specified was not identified 318 Company SsrmWssed. Does nS H-24516: Subchronic Toxicity 90-Day Gavage Study in Rats with One-Generation Reproduction Evaluations TABLE 44 (CONTINUED) MICROSCOPIC OBSERVATIONS IN MALE RATS LISTING INDIVIDUAL ANIMALS AFF NEOPLASTIC AND NON-NEOPLASTIC (90-DAY EXPOSURE EVALUATION INCLUDING EARLY DEATHS FROM THE REPRODUCTION EV LESIONS DIGESTIVE SYSTEM TREATMENT (mg/kg/day) LESION INCID 0 25 I III LIVER HYPERTROPHY, HEPATOCYTE, CENTRILOBULAR. FATTY CHANGE, MEDIAN CLEFT. FATTY CHANGE, CENTRILOBULAR. (10) (10) 643189 643300 643189 64318 64326 64318 64329 Figure in parentheses is number of animals microscopically examined for this tissue The absence of a number indicates the lesion specified was not identified 319 Qompany Sanitized. Doe H-24516: Subchronic Toxicity 90-Day Gavage Study in Rats with One-Generation Reproduction Evaluations TABLE 44 (CONTINUED) MICROSCOPIC OBSERVATIONS IN MALE RATS LISTING INDIVIDUAL ANIMALS AFFE NEOPLASTIC AND NON-NEOPLASTIC (90-DAY EXPOSURE EVALUATION INCLUDING EARLY DEATHS FROM THE REPRODUCTION EVA LESIONS DIGESTIVE SYSTEM TREATMENT (nig/kg/day) LESION INCIDE 0 25 I III PANCREAS NO ABNORMALITY DETECTED (10) 643143 643150 643185 643189 643204 643205 643235 INFLAMMATION, SUBACUTE/CHRONIC. ATROPHY. 643241 643288 643241 643300 Figure in parentheses is number of animals microscopically examined for this tissue The absence of a number indicates the lesion specified was not identified 320 osipany Sanitized. Does n H-24516: Subchronic Toxicity 90-Day Gavage Study in Rats with One-Generation Reproduction Evaluations TABLE 44 (CONTINUED) MICROSCOPIC OBSERVATIONS IN MALE RATS LISTING INDIVIDUAL ANIMALS AFF NEOPLASTIC AND NON-NEOPLASTIC (90-DAY EXPOSURE EVALUATION INCLUDING EARLY DEATHS FROM THE REPRODUCTION EV LESIONS DIGESTIVE SYSTEM TREATMENT (mg/kg/day) LESION INCID 0 25 I III ESOPHAGUS NO ABNORMALITY DETECTED INFLAMMATION, SUBACUTE/CHROMIC. EDEMA. (10) 643143 643150 643185 643189 643204 643205 643235 643241 643288 643300 Figure in parentheses is number of animals microscopically examined for this tissue The absence of a number indicates the lesion specified was not identified 321 eompa^garitfeed. Does not H-24516: Subchronic Toxicity 90-Day Gavage Study in Rats with One-Generation Reproduction Evaluations TABLE 44 (CONTINUED) MICROSCOPIC OBSERVATIONS IN MALE RATS LISTING INDIVIDUAL ANIMALS AFF NEOPLASTIC AND NON-NEOPLASTIC (90-DAY EXPOSURE EVALUATION INCLUDING EARLY DEATHS FROM THE REPRODUCTION EV LESIONS DIGESTIVE SYSTEM TREATMENT (mg/kg/day) LESION INCID 0 25 I III STOMACH NO ABNORMALITY DETECTED (10) 643143 643150 643185 643189 643204 643205 643235 643241 643288 643300 Figure in parentheses is number of animals microscopically examined for this tissue The absence of a number indicates the lesion specified was not identified 322 ^m|NmySa^tmJ. Does ne H-24516: Subchronic Toxicity 90-Day Gavage Study in Rats with One-Generation Reproduction Evaluations TABLE 44 (CONTINUED) MICROSCOPIC OBSERVATIONS IN MALE RATS LISTING INDIVIDUAL ANIMALS AFF NEOPLASTIC AND NON-NEOPLASTIC (90-DAY EXPOSURE EVALUATION INCLUDING EARLY DEATHS FROM THE REPRODUCTION EV LESIONS DIGESTIVE SYSTEM TREATMENT (mg/kg/day) LESION INCID 0 25 I III DUODENUM NO ABNORMALITY DETECTED (10) 643143 643150 643185 643189 643204 643205 643235 643241 643288 643300 Figure in parentheses is number of animals microscopically examined for this tissue The absence of a number indicates the lesion specified was not identified 323 ompasy anRteed. Does no H-24516: Subchronic Toxicity 90-Day Gavage Study in Rats with One-Generation Reproduction Evaluations TABLE 44 (CONTINUED) MICROSCOPIC OBSERVATIONS IN MALE RATS LISTING INDIVIDUAL ANIMALS AFF NEOPLASTIC AND NON-NEOPLASTIC (90-DAY EXPOSURE EVALUATION INCLUDING EARLY DEATHS FROM THE REPRODUCTION EV LESIONS DIGESTIVE SYSTEM | LESION INCID TREATMENT 0 25 (ing/kg/day) I III JEJUNUM NO ABNORMALITY DETECTED (10) 643143 643150 643185 643189 643204 643205 643235 643241 643288 643300 Figure in parentheses is number of animals microscopically examined for this tissue The absence of a number indicates the lesion specified was not identified 324 Conmanyganteed. Does not H-24516: Subchronic Toxicity 90-Day Gavage Study in Rats with One-Generation Reproduction Evaluations TABLE 44 (CONTINUED) MICROSCOPIC OBSERVATIONS IN MALE RATS LISTING INDIVIDUAL ANIMALS AFFE NEOPLASTIC AND NON-NEOPLASTIC (90-DAY EXPOSURE EVALUATION INCLUDING EARLY DEATHS FROM THE REPRODUCTION EV LESIONS DIGESTIVE SYSTEM TREATMENT (nig/kg/day) LESION INCID 0 25 I III ILEUM NO ABNORMALITY DETECTED (10)' 643143 643150 643185 643189 643204 643205 643235 643241 643288 643300 Figure in parentheses is number of animals microscopically examined for this tissue The absence of a number indicates the lesion specified was not identified 325 eoremany Sanitized. Does not H-24516: Subchronic Toxicity 90-Day Gavage Study in Rats with One-Generation Reproduction Evaluations TABLE 44 (CONTINUED) MICROSCOPIC OBSERVATIONS IN MALE RATS LISTING INDIVIDUAL ANIMALS AFF NEOPLASTIC AND NON-NEOPLASTIC (90-DAY EXPOSURE EVALUATION INCLUDING EARLY DEATHS FROM THE REPRODUCTION EV LESIONS DIGESTIVE SYSTEM TREATMENT (mg/kg/day) LESION INCID 0 25 I III CECUM NO ABNORMALITY DETECTED (10) 643143 643150 643185 643189 643204 643205 643235 643241 643288 643300 Figure in parentheses is number of animals microscopically examined for this tissue The absence of a number indicates the lesion specified was not identified 326 'Conwany Sanitized. Does not cont H-24516: Subchronic Toxicity 90-Day Gavage Study in Rats with One-Generation Reproduction Evaluations TABLE 44 (CONTINUED) MICROSCOPIC OBSERVATIONS IN MALE RATS LISTING INDIVIDUAL ANIMALS AFFE NEOPLASTIC AND NON-NEOPLASTIC (90-DAY EXPOSURE EVALUATION INCLUDING EARLY DEATHS FROM THE REPRODUCTION EVA LESIONS DIGESTIVE SYSTEM TREATMENT (mg/kg/day) LESION INCIDE 0 25 I III COLON NO ABNORMALITY DETECTED (10) 643143 643150 643185 643189 643204 643205 643235 643241 643288 643300 Figure in parentheses is number of animals microscopically examined for this tissue The absence of a number indicates the lesion specified was not identified 327 Company SanWzed. Does not con H-24516: Subchronic Toxicity 90-Day Gavage Study in Rats with One-Generation Reproduction Evaluations TABLE 44 (CONTINUED) MICROSCOPIC OBSERVATIONS IN MALE RATS LISTING INDIVIDUAL ANIMALS AFF NEOPLASTIC AND NON-NEOPLASTIC (90-DAY EXPOSURE EVALUATION INCLUDING EARLY DEATHS FROM THE REPRODUCTION EV LESIONS DIGESTIVE SYSTEM TREATMENT (nig/kg/day) LESION INCID 0 25 I III RECTUM NO ABNORMALITY DETECTED (10) 643143 643150 643185 643189 643204 643205 643235 643241 643288 643300 Figure in parentheses is number of animals microscopically examined for this tissue The absence of a number indicates the lesion specified was not identified 328 Company Sanieiwl. Does naiaw H-24516: Subchronic Toxicity 90-Day Gavage Study in Rats with One-Generation Reproduction Evaluations TABLE 44 (CONTINUED) MICROSCOPIC OBSERVATIONS IN MALE RATS LISTING INDIVIDUAL ANIMALS AFFE NEOPLASTIC AND NON-NEOPLASTIC (90-DAY EXPOSURE EVALUATION INCLUDING EARLY DEATHS FROM THE REPRODUCTION EV LESIONS DIGESTIVE SYSTEM TREATMENT (nig/kg/day) LESION INCID 0 25 I III SALIVARY GLANDS NO ABNORMALITY DETECTED ' (10) 643143 643150 643185 643189 643204 643205 643235 643241 643288 643300 Figure in parentheses is number of animals microscopically examined for this tissue The absence of a number indicates the lesion specified was not identified 329 Company SanitSzed. Does not c H-24516: Subchronic Toxicity 90-Day Gavage Study in Rats with One-Generation Reproduction Evaluations TABLE 44 (CONTINUED) MICROSCOPIC OBSERVATIONS IN MALE RATS LISTING INDIVIDUAL ANIMALS AFF NEOPLASTIC AND NON-NEOPLASTIC (90-DAY EXPOSURE EVALUATION INCLUDING EARLY DEATHS FROM THE REPRODUCTION EV LESIONS URINARY SYSTEM KIDNEYS NO ABNORMALITY DETECTED NEPHROPATHY, CHRONIC PROGRESSIVE. [ LESION INCID TREATMENT 25 (mg/kg/day) III (10) 643143 643185 643189 643205 643235 643288 643150 643204 643241 643300 (10) 643173 643179 643240 643264 643272 643290 643308 643180 643228 643292 HYPERTROPHY, TUBULAR. Figure in parentheses is number of animals microscopically examined for this tissue The absence of a number indicates the lesion specified was not identified 330 Company Sanitized. Does not H-24516: Subchronic Toxicity 90-Day Gavage Study in Rats with One-Generation Reproduction Evaluations TABLE 44 (CONTINUED) MICROSCOPIC OBSERVATIONS IN MALE RATS LISTING INDIVIDUAL ANIMALS AFF NEOPLASTIC AND NON-NEOPLASTIC (90-DAY EXPOSURE EVALUATION INCLUDING EARLY DEATHS FROM THE REPRODUCTION EV LESIONS URINARY SYSTEM TREATMENT (mg/kg/day) LESION INCID 0 25 I III KIDNEYS HYPERTROPHY, TUBULAR. HYDRONEPHROSIS, UNILATERAL. HYDRONEPHROSIS, BILATERAL. (10) (10) Figure in parentheses is number of animals microscopically examined for this tissue The absence of a number indicates the lesion specified was not identified 331 Company SanISteed. Does n H-24516: Subchronic Toxicity 90-Day Gavage Study in Rats with One-Generation Reproduction Evaluations TABLE 44 (CONTINUED) MICROSCOPIC OBSERVATIONS IN MALE RATS LISTING INDIVIDUAL ANIMALS AFF NEOPLASTIC AND NON-NEOPLASTIC (90-DAY EXPOSURE EVALUATION INCLUDING EARLY DEATHS FROM THE REPRODUCTION EV LESIONS URINARY SYSTEM TREATMENT (mg/kg/day) LESION INCID 0 25 -- III URINARY BLADDER NO ABNORMALITY DETECTED (10) 643143 643150 643185 643189 643204 643205 643235 643241 643288 643300 Figure in parentheses is number of animals microscopically examined for this tissue The absence of a number indicates the lesion specified was not identified 332 "eiWM"w '<*<--<1 Bia "ot H-24516: Subchronic Toxicity 90-Day Gavage Study in Rats with One-Generation Reproduction Evaluations TABLE 44 (CONTINUED) MICROSCOPIC OBSERVATIONS IN MALE RATS LISTING INDIVIDUAL ANIMALS AFF NEOPLASTIC AND NON-NEOPLASTIC (90-DAY EXPOSURE EVALUATION INCLUDING EARLY DEATHS FROM THE REPRODUCTION EV LESIONS RESPIRATORY SYSTEM TREATMENT (nig/kg/day) LESION INCID 0 25 I III LUNGS NO ABNORMALITY DETECTED INFLAMMATION, SUBACUTE/CHRONIC. INFLAMMATION, GRAMULOMATOUS. (10) 643143 643150 643185 643189 643235 643241 643288 643300 643204 643205 Figure in parentheses is number of animals microscopically examined for this tissue The absence of a number indicates the lesion specified was not identified 333 Company Sanitized. Does not H-24516: Subchronic Toxicity 90-Day Gavage Study in Rats with One-Generation Reproduction Evaluations TABLE 44 (CONTINUED) MICROSCOPIC OBSERVATIONS IN MALE RATS LISTING INDIVIDUAL ANIMALS AFFE NEOPLASTIC AND NON-NEOPLASTIC (90-DAY EXPOSURE EVALUATION INCLUDING EARLY DEATHS FROM THE REPRODUCTION EV LESIONS RESPIRATORY SYSTEM TREATMENT (ing/kg/day) LESION INCID 0 25 I III TRACHEA NO ABNORMALITY DETECTED (10) 643143 643150 643185 643189 643204 643205 643235 643241 643288 643300 Figure in parentheses is number of animals microscopically examined for this tissue The absence of a number indicates the lesion specified was not identified 334 Company Sanitized. Does no H-24516: Subchronic Toxicity 90-Day Gavage Study in Rats with One-Generation Reproduction Evaluations TABLE 44 (CONTINUED) MICROSCOPIC OBSERVATIONS IN MALE RATS LISTING INDIVIDUAL ANIMALS AFF NEOPLASTIC AND NON-NEOPLASTIC (90-DAY EXPOSURE EVALUATION INCLUDING EARLY DEATHS FROM THE REPRODUCTION EV LESIONS RESPIRATORY SYSTEM TREATMENT (ing/kg/day) LESION INCID 0 25 I III PHARYNX/LARYNX NO ABNORMALITY DETECTED HEMORRHAGE. (10) 643143 643150 643185 643189 643204 643205 643235 643241 643288 643300 Figure in parentheses is number of animals microscopically examined for this tissue The absence of a number indicates the lesion specified was not identified 335 Company Sanitized. Does not H-24516: Subchronic Toxicity 90-Day Gavage Study in Rats with One-Generation Reproduction Evaluations TABLE 44 (CONTINUED) MICROSCOPIC OBSERVATIONS IN MALE RATS LISTING INDIVIDUAL ANIMALS AFF NEOPLASTIC AND NON-NEOPLASTIC (90-DAY EXPOSURE EVALUATION INCLUDING EARLY DEATHS FROM THE REPRODUCTION EV LESIONS RESPIRATORY SYSTEM NOSE NO ABNORMALITY DETECTED TREATMENT (mg/.kg/day) INFLAMMATION, SUBACUTE/CHRONIC. HYPERPLASIA/HYPERTROPHY, TRANSITIONAL CELL, EPITHELIUM. DEGENERATION/NECROSIS, RESPIRATORY, EPITHELIUM. DEGENERATION, AMELOBLASTS. LESION INCID 0 25 I III (10) 643143 643150 643185 643189 643204 643205 643235 643241 643288 643300 (10) 64317 64317 64318 64322 64324 64326 64327 64329 64329 64330 Figure in parentheses is number of animals microscopically examined for this tissue The absence of a number indicates the lesion specified was not identified 336 Company Sanitized. Does n H-245I6: Subchronic Toxicity 90-Day Gavage Study in Rats with One-Generation Reproduction Evaluations TABLE 44 (CONTINUED) MICROSCOPIC OBSERVATIONS IN MALE RATS LISTING INDIVIDUAL ANIMALS AFFE NEOPLASTIC AND NON-NEOPLASTIC (90-DAY EXPOSURE EVALUATION INCLUDING EARLY DEATHS FROM THE REPRODUCTION EV LESIONS RESPIRATORY SYSTEM TREATMENT (ing/kg/day) LESION INCID 0 25 I III NOSE DEGENERATION, AMELOBLASTS. (10) (10) Figure in parentheses is number of animals microscopically examined for this tissue The absence of a number indicates the lesion specified was not identified 337 eompamsf Sanitized. Does no H-24516: Subchronic Toxicity 90-Day Gavage Study in Rats with One-Generation Reproduction Evaluations TABLE 44 (CONTINUED) MICROSCOPIC OBSERVATIONS IN MALE RATS LISTING INDIVIDUAL ANIMALS APFE NEOPLASTIC AND NON-NEOPLASTIC (90-DAY EXPOSURE EVALUATION INCLUDING EARLY DEATHS FROM THE REPRODUCTION EV LESIONS CARDIOVASCULAR SYSTEM TREATMENT (nig/kg/day) LESION INCIDE 0 25 III HEART NO ABNORMALITY DETECTED (10) 643143 643150 643185 643241 643288 CARDIOMYOPATHY. INFLAMMATION, SUBACUTE/CHRONIC. 643189 643204 643205 643235 643300 Figure in parentheses is number of animals microscopically examined for this tissue The absence of a number indicates the lesion specified was not identified 338 CompanySanRteed. Does not H-24516: Subchronic Toxicity 90-Day Gavage Study in Rats with One-Generation Reproduction Evaluations TABLE 44 (CONTINUED) MICROSCOPIC OBSERVATIONS IN MALE RATS LISTING INDIVIDUAL ANIMALS AFFE NEOPLASTIC AND NON-NEOPLASTIC (90-DAY EXPOSURE EVALUATION INCLUDING EARLY DEATHS FROM THE REPRODUCTION EVA LESIONS CARDIOVASCULAR SYSTEM TREATMENT (nig/kg/day) LESION INCIDE 0 25 I III AORTA MO ABNORMALITY DETECTED (10) 643143 643150 643185 643189 643204 643205 643235 643241 643288 643300 Figure in parentheses is number of animals microscopically examined for this tissue The absence of a number indicates the lesion specified was not identified 339 Company Sanitized. Doe H-24516: Subchronic Toxicity 90-Day Gavage Study in Rats with One-Generation Reproduction Evaluations TABLE 44 (CONTINUED) MICROSCOPIC OBSERVATIONS IN MALE RATS LISTING INDIVIDUAL ANIMALS AFF NEOPLASTIC AND NON-NEOPLASTIC (90-DAY EXPOSURE EVALUATION INCLUDING EARLY DEATHS FROM THE REPRODUCTION EV LESIONS LYMPHATIC AND HEMATOPOIETIC SYSTEM TREATMENT (mg/kg/day) LESION INCID 0 25 I III SPLEEN NO ABNORMALITY DETECTED (10) 643143 643150 643185 643189 643204 643205 643235 643241 643288 643300 Figure in parentheses is number of animals microscopically examined for this tissue The absence of a number indicates the lesion specified was not identified 340 Company Sanitized. Do H-24516: Subchronic Toxicity 90-Day Gavage Study in Rats with One-Generation Reproduction Evaluations TABLE 44 (CONTINUED) MICROSCOPIC OBSERVATIONS IN MALE RATS LISTING INDIVIDUAL ANIMALS AFF NEOPLASTIC AND NON-NEOPLASTIC (90-DAY EXPOSURE EVALUATION INCLUDING EARLY DEATHS FROM THE REPRODUCTION EV LESIONS LYMPHATIC AND HEMATOPOIETIC SYSTEM TREATMENT (mg/kg/day) LESION INCID 0 25 I III THYMUS NO ABNORMALITY DETECTED ATROPHY. (10) 643143 643150 643185 643189 643204 643205 643235 643241 643288 643300 Figure in parentheses is number of animals microscopically examined for this tissue The absence of a number indicates the lesion specified was not identified 341 Company Sanitized. D H-24516: Subchronic Toxicity 90-Day Gavage Study in Rats with One-Generation Reproduction Evaluations TABLE 44 (CONTINUED) MICROSCOPIC OBSERVATIONS IN MALE RATS LISTING INDIVIDUAL ANIMALS AFFE NEOPLASTIC AND NON-NEOPLASTIC (90-DAY EXPOSURE EVALUATION INCLUDING EARLY DEATHS FROM THE REPRODUCTION EV LESIONS LYMPHATIC AND HEMATOPOIETIC SYSTEM TREATMENT (ing/kg/day) LESION INCID 0 25 I III MANDIBXJIAR LYMPH NODE NO ABNORMALITY DETECTED (10) 643143 643150 643185 643189 643204 643205 643235 643241 643288 643300 Figure in parentheses is number of animals microscopically examined for this tissue The absence of a number indicates the lesion specified was not identified 342 Company Sanitized. Does no H-24516: Subchronic Toxicity 90-Day Gavage Study in Rats with One-Generation Reproduction Evaluations TABLE 44 (CONTINUED) MICROSCOPIC OBSERVATIONS IN MALE RATS LISTING INDIVIDUAL ANIMALS AFF NEOPLASTIC AND NON-NEOPLASTIC (90-DAY EXPOSURE EVALUATION INCLUDING EARLY DEATHS FROM THE REPRODUCTION EV LESIONS LYMPHATIC AND HEMATOPOIETIC SYSTEM TREATMENT (mg/kg/day) LESION INCID 0 25 I III MESENTERIC LYMPH NODE NO ABNORMALITY DETECTED (10) 643143 643150 643185 643189 643204 643205 643235 643241 643288 643300 Figure in parentheses is number of animals microscopically examined for this tissue The absence of a number indicates the lesion specified was not identified 343 Company Sanitized. Does n H-24516: Subchronic Toxicity 90-Day Gavage Study in Rats with One-Generation Reproduction Evaluations TABLE 44 (CONTINUED) MICROSCOPIC OBSERVATIONS IN MALE RATS LISTING INDIVIDUAL ANIMALS AFF NEOPLASTIC AND NON-NEOPLASTIC (90-DAY EXPOSURE EVALUATION INCLUDING EARLY DEATHS FROM THE REPRODUCTION EV LESIONS LYMPHATIC AND HEMATOPOIETIC SYSTEM TREATMENT (mg/kg/day) LESION INCID 0 25 I III BONE MARROW NO ABNORMALITY DETECTED HYPERPLASIA, GRANULOCYTIC. (10) 643143 643150 643185 643189 643204 643205 643235 643241 643288 643300 Figure in parentheses is number of animals microscopically examined for this tissue The absence of a number indicates the lesion specified was not identified 344 Company SanRteed. Does n H-24516: Subchronic Toxicity 90-Day Gavage Study in Rats with One-Generation Reproduction Evaluations TABLE 44 (CONTINUED) MICROSCOPIC OBSERVATIONS IN MALE RATS LISTING INDIVIDUAL ANIMALS AFFE NEOPLASTIC AND NON-NEOPLASTIC (90-DAY EXPOSURE EVALUATION INCLUDING EARLY DEATHS FROM THE REPRODUCTION EV LESIONS ENDOCRINE SYSTEM TREATMENT (nig/kg/day) LESION INCID 0 25 I III PITUITARY GLAND (10) NO ABNORMALITY DETECTED 643143 . 643150 643185 643189 643204 643205 643235 643241 643288 643300 Figure in parentheses is number of animals microscopically examined for this tissue The absence of a number indicates the lesion specified was not identified 345 Company Sanitized. Does not con H-24516: Subchronic Toxicity 90-Day Gavage Study in Rats with One-Generation Reproduction Evaluations TABLE 44 (CONTINUED) MICROSCOPIC OBSERVATIONS IN MALE RATS LISTING INDIVIDUAL ANIMALS AFF NEOPLASTIC AND NON-NEOPLASTIC (90-DAY EXPOSURE EVALUATION INCLUDING EARLY DEATHS FROM THE REPRODUCTION EV LESIONS ENDOCRINE SYSTEM THYROID GLAND NO ABNORMALITY DETECTED INFLAMMATION, SUBACUTE/CHRONIC. HYPERTROPHY, FOLLICULAR. | LESION INCID TREATMENT 0 25 (mg/kg/day) I III (10) (10) 643150 643179 643235 ALTERATION, COLLOID. 643143 643185 643189 643204 643205 643235 643241 643288 643300 643173 643180 643228 643240 643264 643272 643290 643292 643308 Figure in parentheses is number of animals microscopically examined for this tissue The absence of a number indicates the lesion specified was not identified 346 Company SanfSfeed. Does no H-24516: Subchronic Toxicity 90-Day Gavage Study in Rats with One-Generation Reproduction Evaluations TABLE 44 (CONTINUED) MICROSCOPIC OBSERVATIONS IN MALE RATS LISTING INDIVIDUAL ANIMALS AFF NEOPLASTIC AND NON-NEOPLASTIC (90-DAY EXPOSURE EVALUATION INCLUDING EARLY DEATHS FROM THE REPRODUCTION EV LESIONS ENDOCRINE SYSTEM TREATMENT (mg/kg/day) LESION INCID 0 25 I III PARATHYROID GLANDS NO ABNORMALITY DETECTED (8) 643143 643150 643185 643204 643205 643235 643241 643300 Figure in parentheses is number of animals microscopically examined for this tissue The absence of a number indicates the lesion specified was not identified 347 eompany Sanitized. Does not c H-24516: Subchronic Toxicity 90-Day Gavage Stady in Rats with One-Generation Reproduction Evaluations TABLE 44 (CONTINUED) MICROSCOPIC OBSERVATIONS IN MALE RATS LISTING INDIVIDUAL ANIMALS AFF NEOPLASTIC AND NON-NEOPLASTIC (90-DAY EXPOSURE EVALUATION INCLUDING EARLY DEATHS FROM THE REPRODUCTION EV LESIONS ENDOCRINE SYSTEM TREATMENT (mg/kg/day) LESION INCID 0 25 1 III ADRENAL GLANDS NO ABNORMALITY DETECTED (10) 643143 643150 643185 643189 643204 643205 643235 643241 643288 643300 Figure in parentheses is number of animals microscopically examined for this tissue The absence of a number indicates the lesion specified was not identified 348 Company Sanitized. Does not H-24516: Subchronic Toxicity 90-Day Gavage Study in Rats with One-Generation Reproduction Evaluations TABLE 44 (CONTINUED) MICROSCOPIC OBSERVATIONS IN MALE RATS LISTING INDIVIDUAL ANIMALS AFF NEOPLASTIC AND NON-NEOPLASTIC (90-DAY EXPOSURE EVALUATION INCLUDING EARLY DEATHS FROM THE REPRODUCTION EV LESIONS NERVOUS SYSTEM TREATMENT (mg/kg/day) LESION INCID 0 25 I III BRAIN NO ABNORMALITY DETECTED (10) 643143 643150 643185 643189 643204 643205 643235 643241 643288 643300 Figure in parentheses is number of animals microscopically examined for this tissue The absence of a number indicates the lesion specified was not identified 349 CompanySanitized. Doe ng H-24516: Subchronic Toxicity 90-Day Gavage Study in Rats with One-Generation Reproduction Evaluations TABLE 44 (CONTINUED) MICROSCOPIC OBSERVATIONS IN MALE RATS LISTING INDIVIDUAL ANIMALS AFFE NEOPLASTIC AND NON-NEOPLASTIC (90-DAY EXPOSURE EVALUATION INCLUDING EARLY DEATHS FROM THE REPRODUCTION EV LESIONS NERVOUS SYSTEM | LESION INCID TREATMENT 0 25 (mg/kg/day) I III SPINAL CORD NO ABNORMALITY DETECTED (10) 643143 643150 643185 643189 643204 643205 643235 643241 643288 643300 Figure in parentheses is number of animals microscopically examined for this tissue The absence of a number indicates the lesion specified was not identified 350 cowpany8OTW^- ^ H-24516: Subchronic Toxicity 90-Day Gavage Study in Rats with One-Generation Reproduction Evaluations TABLE 44 (CONTINUED) MICROSCOPIC OBSERVATIONS IN MALE RATS LISTING INDIVIDUAL ANIMALS AFF NEOPLASTIC AND NON-NEOPLASTIC (90-DAY EXPOSURE EVALUATION INCLUDING EARLY DEATHS FROM THE REPRODUCTION EV LESIONS NERVOUS SYSTEM TREATMENT (mg/kg/day) LESION INCID 0 25 I III SCIATIC NERVE NO ABNORMALITY DETECTED (10) 643143 643150 643185 643189 643204 643205 643235 643241 643288 643300 Figure in parentheses is number of animals microscopically examined for this tissue The absence of a number indicates the lesion specified was not identified 351 Company Sanitized. Does H-24516: Subchronic Toxicity 90-Day Gavage Study in Rats with One-Generation Reproduction Evaluations TABLE 44 (CONTINUED) MICROSCOPIC OBSERVATIONS IN MALE RATS LISTING INDIVIDUAL ANIMALS AFF NEOPLASTIC AND NON-NEOPLASTIC (90-DAY EXPOSURE EVALUATION INCLUDING EARLY DEATHS FROM THE REPRODUCTION EV LESIONS MUSCULAR AND SKELETAL SYSTEM TREATMENT (mg/kg/day) LESION INCID 0 25 I III SKELETAL MUSCLE NO ABNORMALITY DETECTED - (10) 643143 643150 643185 643189 643204 643205 643235 643241 643288 643300 Figure in parentheses is number of animals microscopically examined for this tissue The absence of a number indicates the lesion specified was not identified 352 Company Sanitized. Doe H-24516: Subchronic Toxicity 90-Day Gavage Study in Rats with One-Generation Reproduction Evaluations TABLE 44 (CONTINUED) MICROSCOPIC OBSERVATIONS IN MALE RATS LISTING INDIVIDUAL ANIMALS AFF NEOPLASTIC AND NON-NEOPLASTIC (90-DAY EXPOSURE EVALUATION INCLUDING EARLY DEATHS FROM THE REPRODUCTION EV LESIONS MUSCULAR AND SKELETAL SYSTEM TREATMENT (nig/kg/day) LESIOM INCID 0 25 I III FEMUR/KNEE JOINT NO ABNORMALITY DETECTED . (10) 643143 643150 643185 643189 643204 643205 643235 643241 643288 643300 Figure in parentheses is number of animals microscopically examined for this tissue The absence of a number indicates the lesion specified was not identified 353 Company SanSBzed. D H-24516: Subchronic Toxicity 90-Day Gavage Study in Rats with One-Generation Reproduction Evaluations TABLE 44 (CONTINUED) MICROSCOPIC OBSERVATIONS IN MALE RATS LISTING INDIVIDUAL ANIMALS AFF NEOPLASTIC AND NON-NEOPLASTIC (90-DAY EXPOSURE EVALUATION INCLUDING EARLY DEATHS FROM THE REPRODUCTION EV LESIONS MUSCULAR AND SKELETAL SYSTEM | LESION INCID TREATMENT 0 25 (ing/kg/day) I III STERNUM NO ABNORMALITY DETECTED ^ (10) 643143 643150 643185 643189 643204 643205 643235 643241 643288 643300 Figure in parentheses is number of animals microscopically examined for this tissue The absence of a number indicates the lesion specified was not identified 354 Company SanfSIzed. Doe H-24516: Subchronic Toxicity 90-Day Gavage Study in Rats with One-Generation Reproduction Evaluations TABLE 44 (CONTINUED) MICROSCOPIC OBSERVATIONS IN MALE RATS LISTING INDIVIDUAL ANIMALS AFF NEOPLASTIC AND NON-NEOPLASTIC (90-DAY EXPOSURE EVALUATION INCLUDING EARLY DEATHS FROM THE REPRODUCTION EV LESIONS MUSCULAR AND SKELETAL SYSTEM TREATMENT (mg/kg/day) LESION INCID 25 III MANDIBLE NO ABNORMALITY DETECTED DEGENERATION, AMELOBLASTS. (10) 643143 643150 643185 643189 643204 643205 643235 643241 643288 643300 (10) 64317 64317 64318 64322 64324 64326 64327 64329 64329 64330 Figure in parentheses is number of animals microscopically examined for this tissue The absence of a number indicates the lesion specified was not identified 355 Company San?S'zed. Does n H-24516: Subchronic Toxicity 90-Day Gavage Study in Rats with One-Generation Reproduction Evaluations TABLE 44 (CONTINUED) MICROSCOPIC OBSERVATIONS IN MALE RATS LISTING INDIVIDUAL ANIMALS AFF NEOPLASTIC AND NON-NEOPLASTIC (90-DAY EXPOSURE EVALUATION INCLUDING EARLY DEATHS FROM THE REPRODUCTION E LESIONS REPRODUCTIVE SYSTEM TREATMENT (mg/kg/day) LESIOM INCI 0 25 I III TESTES NO ABNORMALITY DETECTED SPERMATID RETENTION, SEMINIFEROUS TUBULES. (10) 643143 643150 643185 643189 643204 643205 643235 643241 643288 643300 Figure in parentheses is number of animals microscopically examined for this tissue The absence of a number indicates the lesion specified was not identified 356 iw rfli~w4.B MO. Company Sanitized. Pe H-24516: Subchronic Toxicity 90-Day Gavage Study in Rats with One-Generation Reproduction Evaluations TABLE 44 (CONTINUED) MICROSCOPIC OBSERVATIONS IN MALE RATS LISTING INDIVIDUAL ANIMALS AF NEOPLASTIC AND NON-NEOPLASTIC (90-DAY EXPOSURE EVALUATION INCLUDING EARLY DEATHS FROM THE REPRODUCTION E LESIONS REPRODUCTIVE SYSTEM TREATMENT (mg/kg/day) LESION INC 0 25 I III EPIDIDYMIDES NO ABNORMALITY DETECTED (10) 643143 643150 643185 643189 643204 643205 643235 643241 643288 643300 Figure in parentheses is number of animals microscopically examined for this tissue The absence of a number indicates the lesion specified was not identified 357 Company Sanitized. Does H-24516: Subchronic Toxicity 90-Day Gavage Study in Rats with One-Generation Reproduction Evaluations TABLE 44 (CONTINUED) MICROSCOPIC OBSERVATIONS IN MALE RATS LISTING INDIVIDUAL ANIMALS AF NEOPLASTIC AND NON-NEOPLASTIC (90-DAY EXPOSURE EVALUATION INCLUDING EARLY DEATHS FROM THE REPRODUCTION E LESIONS REPRODUCTIVE SYSTEM TREATMENT (mg/kg/day) LESION INCI 0 25 I III PROSTATE NO ABNORMALITY DETECTED INFLAMMATION, SUBACUTE/CHRONIC. (10) 643143 643150 643185 643189 643204 643205 643235 643241 643300 643288 Figure in parentheses is number of animals microscopically examined for this tissue The absence of a number indicates the lesion specified was not identified 358 ISompany SanHIzed. Does H-24516: Subchronic Toxicity 90-Day Gavage Study in Rats with One-Generation Reproduction Evaluations TABLE 44 (CONTINUED) MICROSCOPIC OBSERVATIONS IN MALE RATS LISTING INDIVIDUAL ANIMALS AFF NEOPLASTIC AND NON-NEOPLASTIC (90-DAY EXPOSURE EVALUATION INCLUDING EARLY DEATHS FROM THE REPRODUCTION E LESIONS REPRODUCTIVE SYSTEM TREATMENT (ing/kg/day) LESION INCI 0 25 I III SEMINAL VESICLES NO ABNORMALITY DETECTED - (10) 643143 643150 643185 643189 643204 643205 643235 643241 643288 643300 Figure in parentheses is number of animals microscopically examined for this tissue The absence of a number indicates the lesion specified was not identified 359 Company Sanded. Does m H-24516: Subchronic Toxicity 90-Day Gavage Study in Rats with One-Generation Reproduction Evaluations TABLE 44 (CONTINUED) MICROSCOPIC OBSERVATIONS IN MALE RATS LISTING INDIVIDUAL ANIMALS AFF NEOPLASTIC AND NON-NEOPLASTIC (90-DAY EXPOSURE EVALUATION INCLUDING EARLY DEATHS FROM THE REPRODUCTION EV LESIONS CUTANEOUS SYSTEM TREATMENT (mg/kg/day) LESION INCID 0 25 I III SKIN NO ABNORMALITY DETECTED (10) 643143 643150 643185 643189 643204 643205 643235 643241 643288 643300 Figure in parentheses is number of animals microscopically examined for this tissue The absence of a number indicates the lesion specified was not identified 360 "Comoany'SanWzed. Does no H-24516: Subchronic Toxicity 90-Day Gavage Study in Rats with One-Generation Reproduction Evaluations TABLE 44 (CONTINUED) MICROSCOPIC OBSERVATIONS IN MALE RATS LISTING INDIVIDUAL ANIMALS AFF NEOPLASTIC AND NON-NEOPLASTIC (90-DAY EXPOSURE EVALUATION INCLUDING EARLY DEATHS FROM THE REPRODUCTION E LESIONS SPECIAL SENSES SYSTEM TREATMENT (ing/kg/day) LESION INCI 0 25 I III EYE(S) WITH OPTIC NERVE NO ABNORMALITY DETECTED OPTIC NERVE NOT PRESENT. FOLD/ROSETTE, RETINAL. (10) 643143 643150 643185 643189 643204 643235 643241 643288 643300 643205 Figure in parentheses is number of animals microscopically examined for this tissue The absence of a number indicates the lesion specified was not identified 361 Company Sanitized. Doea n H-24516: Subchronic Toxicity 90-Day Gavage Study in Rats with One-Generation Reproduction Evaluations TABLE 44 (CONTINUED) MICROSCOPIC OBSERVATIONS IN MALE RATS LISTING INDIVIDUAL ANIMALS AFFEC NEOPLASTIC AND NON-NEOPLASTIC (ONE-MONTH RECOVERY EVALUATION) LESION INCI LESIONS DIGESTIVE SYSTEM LIVER NECROSIS, FOCAL. INFLAMMATION, SUBACUTE/CHRONIC. TREATMENT (mg/kg/day) HYPERTROPHY, HEPATOCYTE, CENTRILOBULAR. Figure in parentheses is number of animals microscopically examined for this tissue The absence of a number indicates the lesion specified was not identified 362 Company Sanitized. Does no H-24516: Subchronic Toxicity 90-Day Gavage Study in Rats with One-Generation Reproduction Evaluations TABLE 44 (CONTINUED) MICROSCOPIC OBSERVATIONS IN MALE RATS LISTING INDIVIDUAL ANIMALS AFF NEOPLASTIC AND NON-NEOPLASTIC (ONE-MONTH RECOVERY EVALUATION) LESION INCI LESIONS TREATMENT (mg/kg/day) DIGESTIVE SYSTEM LXVER FOCUS FATTY FATTY OF CELLULAR ALTERATION, CHANGE, MEDIAN CLEFT. CHANGE, CENTRILOBULAR. BASOPHILIC. Figure in parentheses is number of animals microscopically examined for this tissue The absence of a number indicates the lesion specified was not identified 363 company Sanitized. Doe H-24516: Subchronic Toxicity 90-Day Gavage Study in Rats with One-Generation Reproduction Evaluations TABLE 44 (CONTINUED) MICROSCOPIC OBSERVATIONS IN MALE RATS LISTING INDIVIDUAL ANIMALS AFFE NEOPLASTIC AND NON-NEOPLASTIC (ONE-MONTH RECOVERY EVALUATION) LESION INCID LESIONS URINARY SYSTEM KIDNEYS NO ABNORMALITY DETECTED TREATMENT (ing/kg/day) NEPHROPATHY, CHRONIC PROGRESSIVE. HYPERTROPHY, TUBULAR. HYDRONEPHROSIS, UNILATERAL. Figure in parentheses is number of animals microscopically examined for this tissue The absence of a number indicates the lesion specified was not identified 364 Company SanWzecS. Doe H-24516: Subchronic Toxicity 90-Day Gavage Study in Rats with One-Generation Reproduction Evaluations TABLE 44 (CONTINUED) MICROSCOPIC OBSERVATIONS IN MALE RATS LISTING INDIVIDUAL ANIMALS AFF NEOPLASTIC AND NON-NEOPLASTIC (ONE-MONTH RECOVERY EVALUATION) LESION INCID LESIONS RESPIRATORY SYSTEM NOSE NO ABNORMALITY DETECTED TREATMENT (mg/kg/day) ODONTODYSPLASIA. DEGENERATION, AMELOBLASTS, Figure in parentheses is number of animals microscopically examined for this tissue The absence of a number indicates the lesion specified was not identified 365 Company Sanitized. Does no H-24516: Subchronic Toxicity 90-Day Gavage Study in Rats with One-Generation Reproduction Evaluations TABLE 44 (CONTINUED) MICROSCOPIC OBSERVATIONS IN MALE RATS LISTING INDIVIDUAL ANIMALS AFF NEOPLASTIC AND NON-NEOPLASTIC (ONE-MONTH RECOVERY EVALUATION) LESION INCID LESIONS TREATMENT (mg/kg/day) LYMPHATIC AND HEMATOPOIETIC SYSTEM SPLEEN NO ABNORMALITY DETECTED THYMUS . NO ABNORMALITY DETECTED MANDIBULAR LYMPH NODE ERYTHROCYTOSIS/ERYTHROPHAGOCYTOSIS, SINUS. Figure in parentheses is number of animals microscopically examined for this tissue The absence of a number indicates the lesion specified was not identified 366 Company Sanitized. Does not conta H-24516: Subchronic Toxicity 90-Day Gavage Study in Rats with One-Generation Reproduction Evaluations TABLE 44 (CONTINUED) MICROSCOPIC OBSERVATIONS IN MALE RATS LISTING INDIVIDUAL ANIMALS AFF NEOPLASTIC AND NON-NEOPLASTIC (ONE-MONTH RECOVERY EVALUATION) LESION INCID LESIONS ENDOCRINE SYSTEM THYROID GLAND ALTERATION, COLLOID. TREATMENT (ing/kg/day) Figure in parentheses is number of animals microscopically examined for this tissue The absence of a number indicates the lesion specified was not identified 367 ^MW Sanded. Does ro H-24516: Subchronic Toxicity 90-Day Gavage Study in Rats with One-Generation Reproduction Evaluations TABLE 44 (CONTINUED) MICROSCOPIC OBSERVATIONS IN MALE RATS LISTING INDIVIDUAL ANIMALS AFF NEOPLASTIC AND NON-NEOPLASTIC (ONE-MONTH RECOVERY EVALUATION) LESION INCI LESIONS MUSCULAR AND SKELETAL SYSTEM MANDIBLE NO ABNORMALITY DETECTED TREATMENT (nig/kg/day) Figure in parentheses is number of animals microscopically examined for this tissue The absence of a number indicates the lesion specified was not identified 368 oroawgw>wi(i Does na? H-24516: Subchronic Toxicity 90-Day Gavage Study in Rats with One-Generation Reproduction Evaluations TABLE 44 (CONTINUED) MICROSCOPIC OBSERVATIONS IN MALE RATS LISTING INDIVIDUAL ANIMALS AFF NEOPLASTIC AND NON-NEOPLASTIC (ONE-MONTH RECOVERY EVALUATION) LESION INCID LESIONS TREATMENT (mg/kg/day) REPRODUCTIVE SYSTEM TESTES DEGENERATION/ATROPHY, SEMINIFEROUS TUBULES, UNILATERAL. DEGENERATION/ATROPHY, SEMINIFEROUS TUBULES, BILATERAL. EPIDIDYMIDES NO ABNORMALITY DETECTED OLIGOSPERMIA/GERM CELL DEBRIS, UNILATERAL. SEMINAL VESICLES NO ABNORMALITY DETECTED Figure in parentheses is number of animals microscopically examined for this tissue The absence of a number indicates the lesion specified was not identified 369 Company Sanitized. Does noS contain H-24516: Subchronic Toxicity 90-Day Gavage Study in Rats with One-Generation Reproduction Evaluations TABLE 44 (CONTINUED) MICROSCOPIC OBSERVATIONS IN MALE RATS LISTING INDIVIDUAL ANIMALS AFF NEOPLASTIC AND NON-NEOPLASTIC (THREE-MONTH RECOVERY EVALUATION) LESIONS DIGESTIVE SYSTEM LIVER NECROSIS, FOCAL. INFLAMMATION, SUBACUTE/CHRONIC. HYPERTROPHY, HEPATOCYTE, CENTRILOBULAR. PATTY CHANGE, MEDIAN CLEFT. FATTY CHANGE, CENTRILOBULAR. TREATMENT (ing/kg/day) LESION INCID 0 25 I III (5) 643210 643145 643210 643232 643265 643268 643232 Figure in parentheses is number of animals microscopically examined for this tissue The absence of a number indicates the lesion specified was not identified 370 ^"PanySaniteed. Does not conta H-24516: Subchronic Toxicity 90-Day Gavage Study in Rats with One-Generation Reproduction Evaluations TABLE 44 (CONTINUED) MICROSCOPIC OBSERVATIONS IN MALE RATS LISTING INDIVIDUAL ANIMALS AFF NEOPLASTIC AND NON-NEOPLASTIC (THREE-MONTH RECOVERY EVALUATION) LESIONS URINARY SYSTEM KIDNEYS NO ABNORMALITY DETECTED CALCULUS\CALCULI. NEPHROPATHY, CHRONIC PROGRESSIVE. INFLAMMATION, SUBACUTE/CHRONIC. HYPERPLASIA, TRANSITIONAL CELL. TREATMENT (mg/kg/day) LESION INCID 0 25 I III (5) 643232 643265 643145 643210 643268 Figure in parentheses is number of animals microscopically examined for this tissue The absence of a number indicates the lesion specified was not identified 371 Company Sanitiml. Does not co H-24516: Subchronic Toxicity 90-Day Gavage Study in Rats with One-Generation Reproduction Evaluations TABLE 44 (CONTINUED) MICROSCOPIC OBSERVATIONS IN MALE RATS LISTING INDIVIDUAL ANIMALS AFF NEOPLASTIC AND NON-NEOPLASTIC (THREE-MONTH RECOVERY EVALUATION) LESION INCID LESIONS RESPIRATORY SYSTEM TREATMENT 0 25 (mg/kg/day) I III NOSE NO ABNORMALITY DETECTED INFLAMMATION, SUBACUTE/CHRONIC, NASOLACRIMAL DUCT. INFLAMMATION, SUBACUTE/CHRONIC. (5) 643210 643232 643265 643145 643268 (5) 64330 64330 64320 64329 64331 HYPERPLASIA/SQUAMOUS METAPLASIA, RESPIRATORY, EPITHELIUM. HYPERPLASIA/HYPERTROPHY, TRANSITIONAL CELL, EPITHELIUM. FRACTURE/CALLUS, TOOTH. DEGENERATION/NECROSIS, RESPIRATORY, DEGENERATION, AMELOBLASTS. EPITHELIUM. 643145 643268 64320 64320 64329 64331 SCHWANNOMA [B]. 64320 [B] Benign tumour Figure in parentheses is number of animals microscopically examined for this tissue The absence of a number indicates the lesion specified was not identified 372 ompanySanitized. Does not ^^1^^ ^ 'fe.^ H-24516: Subchronic Toxicity 90-Day Gavage Study in Rats with One-Generation Reproduction Evaluations TABLE 44 (CONTINUED) MICROSCOPIC OBSERVATIONS IN MALE RATS LISTING INDIVIDUAL ANIMALS APF NEOPLASTIC AND NON-NEOPLASTIC (THREE-MONTH RECOVERY EVALUATION) LESIONS ENDOCRINE SYSTEM TREATMENT (mg/kg/day) LESION INCID 0 25 I III THYROID GLAND ALTERATION, COLLOID. (5) 643145 643210 643232 643265 643268 (5) 643202 643293 643305 643306 643310 Figure in parentheses is number of animals microscopically examined for this tissue The absence of a number indicates the lesion specified was not identified 373 ">PanySalted. Does nog ^w H-24516: Subchronic Toxicity 90-Day Gavage Study in Rats with One-Generation Reproduction Evaluations TABLE 45 MICROSCOPIC OBSERVATIONS IN FEMALE RATS LISTING INDIVIDUAL ANIMALS AF NEOPLASTIC AND NON-NEOPLASTIC (90-DAY EXPOSURE EVALUATION INCLUDING EARLY DEATHS FROM THE REPRODUCTION EV LESIONS DIGESTIVE SYSTEM LIVER NO ABNORMALITY DETECTED NECROSIS, FOCAL. INFLAMMATION, SUBACUTE/CHRONIC. HYPERTROPHY, HEPATOCYTE, CENTRILOBULAR. TREATMENT (mg/kg/day) LESION INCID 0 25 II IV (10) (10) 643354 64332 643362 643361 643362 643374 643398 643406 643436 643463 643477 643486 64332 64336 64338 64338 64339 64339 64341 64343 64345 PATTY CHANGE, MEDIAN CLEFT. 643374 64345 N=11 in Group VIII reflects one reproduction designated animal that died on test day 53. Figure in parentheses is number of animals microscopically examined for this tissue The absence of a number indicates the lesion specified was not identified 374 Does no H-24516: Subchronic Toxicity 90-Day Gavage Study in Rats with One-Generation Reproduction Evaluations TABLE 45 (CONTINUED) MICROSCOPIC OBSERVATIONS IN FEMALE RATS LISTING INDIVIDUAL ANIMALS AF NEOPLASTIC AND NON-NEOPLASTIC (90-DAY EXPOSURE EVALUATION INCLUDING EARLY DEATHS FROM THE REPRODUCTION EV LESIONS DIGESTIVE SYSTEM TREATMENT (mg/kg/day) LESION INCID 0 25 II IV LIVER FATTY CHANGE, MEDIAN CLEFT. PANCREAS NO ABNORMALITY DETECTED ATROPHY. (10) (10) 643398 (10) 643354 643361 643362 643374 643398 643406 643436 643463 643477 643486 (1) 643321 Figure in parentheses is number of animals microscopically examined for this tissue The absence of a number indicates the lesion specified was not identified 375 Sompany Sanitized. Does not con H-24516: Subchronic Toxicity 90-Day Gavage Study in Rats with One-Generation Reproduction Evaluations TABLE 45 (CONTINUED) MICROSCOPIC OBSERVATIONS IN F,EMALE RATS LISTING INDIVIDUAL ANIMALS AFF NEOPLASTIC AND NON-NEOPLASTIC (90-DAY EXPOSURE EVALUATION INCLUDING EARLY DEATHS FROM THE REPRODUCTION EV LESIONS DIGESTIVE SYSTEM ESOPHAGUS NO ABNORMALITY DETECTED INFLAMMATION, SUBACUTE/CHRONIC. TREATMENT (mg/.kg/day) LESION INCID 0 25 II IV (10) 643354 643361 643362 643374 643398 643406 643436 643463 643477 643486 (1) 643321 Figure in parentheses is number of animals microscopically examined for this tissue The absence of a number indicates the lesion specified was not identified 376 "ompany SanWzed. Does not e H-24516: Subchronic Toxicity 90-Day Gavage Study in Rats with One-Generation Reproduction Evaluations TABLE 45 (CONTINUED) MICROSCOPIC OBSERVATIONS IN FEMALE RATS LISTING INDIVIDUAL ANIMALS AF NEOPLASTIC AND NON-NEOPLASTIC (90-DAY EXPOSURE EVALUATION INCLUDING EARLY DEATHS FROM THE REPRODUCTION EV LESIONS DIGESTIVE SYSTEM STOMACH NO ABNORMALITY DETECTED | LESIOM IMCID TREATMENT 0 25 (mg/kg/day) II IV (10) 643354 643361 643362 643374 643398 643406 643436 643463 643477 643486 (1) 64332 Figure in parentheses is number of animals microscopically examined for this tissue The absence of a number indicates the lesion specified was not identified 377 H-24516: Subchronic Toxicity 90-Day Gavage Study in Rats with One-Generation Reproduction Evaluations TABLE 45 (CONTINUED) MICROSCOPIC OBSERVATIONS IN FEMALE RATS LISTING INDIVIDUAL ANIMALS AF NEOPLASTIC AND NON-NEOPLASTIC (90-DAY EXPOSURE EVALUATION INCLUDING EARLY DEATHS FROM THE REPRODUCTION EV LESIONS DIGESTIVE SYSTEM DUODENUM NO ABNORMALITY DETECTED TREATMENT (mg/kg/day) LESION INCID 0 25 II IV (10) 643354 643361 643362 643374 643398 643406 643436 643463 643477 643486 (1) 64332 Figure in parentheses is number of animals microscopically examined for this tissue The absence of a number indicates the lesion specified was not identified 378 t Does no H-24516: Subchronic Toxicity 90-Day Gavage Study in Rats with One-Generation Reproduction Evaluations TABLE 45 (CONTINUED) MICROSCOPIC OBSERVATIONS IN FEMALE RATS LISTING INDIVIDUAL ANIMALS AF NEOPLASTIC AND NON-NEOPLASTIC (90-DAY EXPOSURE EVALUATION INCLUDING EARLY DEATHS FROM THE REPRODUCTION EV LESIONS DIGESTIVE SYSTEM JEJUNUM NO ABNORMALITY DETECTED AUTOLYSIS: NECROPSY AND HISTOLOGY PERFORMED. TREATMENT (mg/kg/day) LESION INCID 0 25 II IV (10) 643354 643361 643362 643374 643398 643406 643436 643463 643477 643486 (1) 64332 Figure in parentheses is number of animals microscopically examined for this tissue The absence of a number indicates the lesion specified was not identified 379 H-24516: Subchronic Toxicity 90-Day Gavage Study in Rats with One-Generation Reproduction Evaluations TABLE 45 (CONTINUED) MICROSCOPIC OBSERVATIONS IN FEMALE RATS LISTING INDIVIDUAL ANIMALS AF NEOPLASTIC AND NON-NEOPLASTIC (90-DAY EXPOSURE EVALUATION INCLUDING EARLY DEATHS FROM THE REPRODUCTION EV LESIONS DIGESTIVE SYSTEM ILEUM NO ABNORMALITY DBTECTED TREATMENT (nig/kg/day) LESION INCID 0 25 II IV (10) 643354 643361 643362 643374 643398 643406 643436 643463 643477 643486 (1) 64332 Figure in parentheses is number of animals microscopically examined for this tissue The absence of a number indicates the lesion specified was not identified 380 SSB"^ SanRteed. Do H-24516: Subchronic Toxicity 90-Day Gavage Study in Rats with One-Generation Reproduction Evaluations TABLE 45 (CONTINUED) MICROSCOPIC OBSERVATIONS IN FEMALE RATS LISTING INDIVIDUAL ANIMALS AF NEOPLASTIC AND NON-NEOPLASTIC (90-DAY EXPOSURE EVALUATION INCLUDING EARLY DEATHS FROM THE REPRODUCTION EV LESIONS DIGESTIVE SYSTEM CECUM NO ABNORMALITY DETECTED TREATMENT (mg/kg/day) LESION INCID 0 25 II IV (10) 643354 643361 643362 643374 643398 643406 643436 643463 643477 643486 (1) 643321 Figure in parentheses is number of animals microscopically examined for this tissue The absence of a number indicates the lesion specified was not identified 381 Conw SanltteHS. Does no H-24516: Subchronic Toxicity 90-Day Gavage Study in Rats with One-Generation Reproduction Evaluations TABLE 45 (CONTINUED) MICROSCOPIC OBSERVATIONS IN FEMALE RATS LISTING INDIVIDUAL ANIMALS AF NEOPLASTIC AND NON-NEOPLASTIC (90-DAY EXPOSURE EVALUATION INCLUDING EARLY DEATHS FROM THE REPRODUCTION EV LESIONS DIGESTIVE SYSTEM COLON NO ABNORMALITY DETECTED TREATMENT (mg/kg/day) LESION INCID 0 25 II IV (10) 643354 643361 643362 643374 643398 643406 643436 643463 643477 643486 (1) 64332 Figure, in parentheses is number of animals microscopically examined for this tissue The absence of a number indicates the lesion specified was not identified 382 company SanSIzed. Does H-24516: Subchronic Toxicity 90-Day Gavage Study in Rats with One-Generation Reproduction Evaluations TABLE 45 (CONTINUED) MICROSCOPIC OBSERVATIONS IN FEMALE RATS LISTING INDIVIDUAL ANIMALS AF NEOPLASTIC AND NON-NEOPLASTIC (90-DAY EXPOSURE EVALUATION INCLUDING EARLY DEATHS FROM THE REPRODUCTION EV LESIONS DIGESTIVE SYSTEM RECTUM NO ABNORMALITY DETECTED TREATMENT (mg/kg/day) LESION INCID 0 25 II IV (10) 643354 643361 643362 643374 643398 643406 643436 643463 643477 643486 (1) 643321 Figure in parentheses is number of animals microscopically examined for this tissue The absence of a number indicates the lesion specified was not identified 383 ^nn^ft-w,^ ffciest H-24516: Subchronic Toxicity 90-Day Gavage Study in Rats with One-Generation Reproduction Evaluations TABLE 45 (CONTINUED) MICROSCOPIC OBSERVATIONS IN FEMALE RATS LISTING INDIVIDUAL ANIMALS AF NEOPLASTIC AND NON-NEOPLASTIC (90-DAY EXPOSURE EVALUATION INCLUDING EARLY DEATHS FROM THE REPRODUCTION EV LESIONS DIGESTIVE'SYSTEM SALIVARY GLANDS NO ABNORMALITY DETECTED TREATMENT (nig/kg/day) LESXON INCID 0 25 II IV (10) (1) 643354 643321 643361 , 643362 643374 643398 643406 643436 643463 643477 643486 Figure in parentheses is number of animals microscopically examined for this tissue The absence of a number indicates the lesion specified was not identified 384 Company Sanitized. Does not c H-24516: Subchronic Toxicity 90-Day Gavage Study in Rats with One-Generation Reproduction Evaluations TABLE 45 (CONTINUED) MICROSCOPIC OBSERVATIONS IN FEMALE RATS LISTING INDIVIDUAL ANIMALS AP NEOPLASTIC AND NON-NEOPLASTIC (90-DAY EXPOSURE EVALUATION INCLUDING EARLY DEATHS FROM THE REPRODUCTION EV LESIONS URINARY SYSTEM KIDNEYS NO ABNORMALITY DETECTED NEPHROPATHY, CHRONIC PROGRESSIVE. NECROSIS, TUBULAR. INFLAMMATION, ACUTE. INFARCT. HYPERPLASIA, TRANSITIONAL CELL. HYDRONEPHROSIS, BILATERAL. CYST. AUTOLYSIS: NECROPSY AND HISTOLOGY PERFORMED. | LESION INCID TREATMENT 0 25 (mg/kg/day) II IV (10) 643354 643361 643374 643406 643463 643486 643362 643398 643477 (10) 64332 64338 64338 64339 64341 64343 64345 64336 64339 64332 64332 64332 64332 643436 Figure in parentheses is number of animals microscopically examined for this tissue The absence of a number indicates the lesion specified was not identified 385 ompany Saniffzed. Does not H-24516: Subchronic Toxicity 90-Day Gavage Study in Rats with One-Generation Reproduction Evaluations TABLE 45 (CONTINUED) MICROSCOPIC OBSERVATIONS IN FEMALE RATS LISTING INDIVIDUAL ANIMALS AF NEOPLASTIC AND NON-NEOPLASTIC (90-DAY EXPOSURE EVALUATION INCLUDING EARLY DEATHS FROM THE REPRODUCTION EV LESIONS URINARY SYSTEM URINARY BLADDER NO ABNORMALITY DETECTED HYPERPLASIA, SIMPLE, TRANSITIONAL CELL. | LESION INCID TREATMENT 0 25 (mg/kg/day) II IV (10) 643354 643361 643362 643374 643398 643406 643436 643463 643477 643486 (1) 643321 Figure in parentheses is number of animals microscopically examined for this tissue The absence of a number indicates the lesion specified was not identified 386 'eernwwM 8)B*waA oes not c H-24516: Subchronic Toxicity 90-Day Gavage Study in Rats with One-Generation Reproduction Evaluations TABLE 45 (CONTINUED) MICROSCOPIC OBSERVATIONS IN FEMALE RATS LISTING INDIVIDUAL ANIMALS AF NEOPLASTIC AND NON-NEOPLASTIC (90-DAY EXPOSURE EVALUATION INCLUDING EARLY DEATHS FROM THE REPRODUCTION EV LESIONS RESPIRATORY SYSTEM LUNGS NO ABNORMALITY DETECTED | LESION INCID TREATMENT 0 25 (mg/kg/day) II IV (10) 643354 643361 643362 643374 643398 643406 643436 643477 643486 (1) 64332 THROMBUS. 643463 Figure in parentheses is number of animals microscopically examined for this tissue The absence of a number indicates the lesion specified was not identified 387 Company SanMzed. Does not c H-24516: Subchronic Toxicity 90-Day Gavage Study in Rats with One-G.eneration Reproduction Evaluations TABLE 45 (CONTINUED) MICROSCOPIC OBSERVATIONS IN FEMALE RATS LISTING INDIVIDUAL ANIMALS AFF NEOPLASTIC AND NON-NEOPLASTIC (90-DAY EXPOSURE EVALUATION INCLUDING EARLY DEATHS FROM THE REPRODUCTION EV LESIONS RESPIRATORY SYSTEM TRACHEA NO ABNORMALITY DETECTED TREATMENT (ing/kg/day) LESION INCID 0 25 II IV (10) 643354 643361 643362 643374 643398 643406 643436 643463 643477 643486 (1) 643321 Figure in parentheses is number of animals microscopically examined for this tissue The absence of a number indicates the lesion specified was not identified 388 H-24516: Subchronic Toxicity 90-Day Gavage Study in Rats with One-Generation Reproduction Evaluations TABLE 45 (CONTINUED) MICROSCOPIC OBSERVATIONS IN FEMALE RATS LISTING INDIVIDUAL ANIMALS AFF NEOPLASTIC AND NON-NEOPLASTIC (90-DAY EXPOSURE EVALUATION INCLUDING EARLY DEATHS FROM THE REPRODUCTION EV LESIONS RESPIRATORY SYSTEM PHARYNX/LARYNX NO ABNORMALITY DETECTED | LESION INCID TREATMENT 0 25 (ing/kg/day) II IV (10) 643354 643361 643362 643374 643398 643406 643436 643463 643477 643486 (1) 643321 Figure in parentheses is number of animals microscopically examined for this tissue The absence of a number indicates the lesion specified was not identified 389 i. Does not con H-24516: Subchronic Toxicity 90-Day Gavage Study in Rats with One-Generation Reproduction Evaluations TABLE 45 (CONTINUED) MICROSCOPIC OBSERVATIONS IN FEMALE RATS LISTING INDIVIDUAL ANIMALS AFF NEOPLASTIC AND NON-NEOPLASTIC (90-DAY EXPOSURE EVALUATION INCLUDING EARLY DEATHS FROM THE REPRODUCTION EV LESIONS RESPIRATORY SYSTEM NOSE NO ABNORMALITY DETECTED INFLAMMATION, SUBACUTE/CHRONIC. FRACTURE/CALLUS, TOOTH. DEGENERATION, AMELOBLASTS. TREATMENT (mg/kg/day) LESION INCID 0 25 II IV (10) 643354 643361 643362 643374 643398 643406 643436 643463 643477 643486 (10) 643321 643324 643364 643380 643390 643396 643410 643433 643458 643389 643389 ? Figure in parentheses is number of animals microscopically examined for this tissue The absence of a number indicates the lesion specified was not identified 390 Company Sanitized. Does noS c H-24516: Subchronic Toxicity 90-Day Gavage Study in Rats with One-Generation Reproduction Evaluations TABLE 45 (CONTINUED) MICROSCOPIC OBSERVATIONS IN FEMALE RATS LISTING INDIVIDUAL ANIMALS AF NEOPLASTIC AND NON-NEOPLASTIC (90-DAY EXPOSURE EVALUATION INCLUDING EARLY DEATHS FROM THE REPRODUCTION EV LESIONS RESPIRATORY SYSTEM TREATMENT (mg/kg/day) LESION INCID 0 25 II IV NOSE DEGENERATION, AMELOBLASTS. (10) (10) Figure in parentheses is number of animals microscopically examined for this tissue The absence of a number indicates the lesion specified was not identified 391 mwSanW2@d. Does H-24516: Subchronic Toxicity 90-Day Gavage Study in Rats with One-Generation Reproduction Evaluations TABLE 45 (CONTINUED) MICROSCOPIC OBSERVATIONS IN FEMALE RATS LISTING INDIVIDUAL ANIMALS AF NEOPLASTIC AND NON-NEOPLASTIC (90-DAY EXPOSURE EVALUATION INCLUDING EARLY DEATHS FROM THE REPRODUCTION EV LESIONS CARDIOVASCULAR SYSTEM HEART NO ABNORMALITY DETECTED TREATMENT (mg/kg/day) LESION INCID 0 25 II IV (10) (1) 643354 643361 643374 643406 643463 643477 643486 CARDIOMYOPATHY, 643362 64332 643398 643436 Figure in parentheses is number of animals microscopically examined for this tissue The absence of a number indicates the lesion specified was not identified 392 'Sompany SanWteed. Does H-24516: Subchronic Toxicity 90-Day Gavage Study in Rats with One-Generation Reproduction Evaluations TABLE 45 (CONTINUED) MICROSCOPIC OBSERVATIONS IN FEMALE RATS LISTING INDIVIDUAL ANIMALS AF NEOPLASTIC AND NON-NEOPLASTIC (90-DAY EXPOSURE EVALUATION INCLUDING EARLY DEATHS FROM THE REPRODUCTION EV LESIONS CARDIOVASCULAR SYSTEM AORTA NO ABNORMALITY DETECTED TREATMENT (mg/kg/day) LESION INCID 0 25 II IV (10) 643354 643361 643362 643374 643398 643406 643436 643463 643477 643486 (1) 643321 Figure in parentheses is number of animals microscopically examined for this tissue The absence of a number indicates the lesion specified was not identified 393 Company Sanitized. Does not co H-24516: Subchronic Toxicity 90-Day Gavage Study in Rats with One-Generation Reproduction Evaluations TABLE 45 (CONTINUED) MICROSCOPIC OBSERVATIONS IN FEMALE RATS LISTING INDIVIDUAL ANIMALS AF NEOPLASTIC AND NON-NEOPLASTIC (90-DAY EXPOSURE EVALUATION INCLUDING EARLY DEATHS FROM THE REPRODUCTION EV LESIONS LYMPHATIC AND HEMATOPOIETIC SYSTEM SPLEEN NO ABNORMALITY DETECTED DEPLETION, LYMPHOID. | LESION INCID TREATMENT 0 25 (ing/kg/day) II IV (10) 643354 643361 643362 643374 643398 643406 643436 643463 643477 643486 (1) 64332 Figure in parentheses is number of animals microscopically examined for this tissue The absence of a number indicates the lesion specified was not identified 394 Company Sanitized. Does n H-24516: Subchronic Toxicity 90-Day Gavage Study in Rats with One-Generation Reproduction Evaluations TABLE 45 (CONTINUED) MICROSCOPIC OBSERVATIONS IN FEMALE RATS LISTING INDIVIDUAL ANIMALS AFF NEOPLASTIC AND NON-NEOPLASTIC (90-DAY EXPOSURE EVALUATION INCLUDING EARLY DEATHS FROM THE REPRODUCTION EV LESIONS LYMPHATIC AND HEMATOPOIETIC SYSTEM THYMUS NO ABNORMALITY DETECTED ATROPHY. | LESION INCID TREATMENT 0 25 (nig/kg/day) II IV (10) 643354 643361 643362 643374 643398 643406 643436 643463 643477 643486 (1) 643321 Figure in parentheses is number of animals microscopically examined for this tissue The absence of a number indicates the lesion specified was not identified 395 "Company Sanfflzed. Do H-24516: Subchronic Toxicity 90-Day Gavage Study in Rats with One-Generation Reproduction Evaluations TABLE 45 (CONTINUED) MICROSCOPIC OBSERVATIONS IN FEMALE RATS LISTING INDIVIDUAL ANIMALS AF NEOPLASTIC AND NON-NEOPLASTIC (90-DAY EXPOSURE EVALUATION INCLUDING EARLY DEATHS FROM THE REPRODUCTION EV LESIONS LYMPHATIC AND HEMATOPOIETIC SYSTEM MANDIBULAR LYMPH NODE NO ABNORMALITY DETECTED TREATMENT (mg/kg/day) LESION INCID 0 25 II IV (10) 643354 643361 643362 643374 643398 643406 643436 643463 643477 643486 (1) 64332 Figure in parentheses is number of animals microscopically examined for this tissue The absence of a number indicates the lesion specified was not identified 396 e^anySanRteed. Does not co H-24516: Subchronic Toxicity 90-Day Gavage Study in Rats with One-Generation Reproduction Evaluations TABLE 45 (CONTINUED) MICROSCOPIC OBSERVATIONS IN FEMALE RATS LISTING INDIVIDUAL ANIMALS AF NEOPLASTIC AND NON-NEOPLASTIC (90-DAY EXPOSURE EVALUATION INCLUDING EARLY DEATHS FROM THE REPRODUCTION EV LESIONS LYMPHATIC AND HEMATOPOIETIC SYSTEM MESENTERIC LYMPH NODE NO ABNORMALITY DETECTED | LESION INCID TREATMENT 0 25 (mg/kg/day) II IV (9) 643354 643361 643362 643374 643398 643406 643436 643463 643477 (1) 64332 Figure in parentheses is number of animals microscopically examined for this tissue The absence of a number indicates the lesion specified was not identified 397 company Sanffized. Dees nol con n-z.tjiu. ouucuromu loxicity 90-Day Gavage Study in Rats with One-Generation Reproduction Evaluations TABLE 45 (CONTINUED) MICROSCOPIC OBSERVATIONS IN FEMALE RATS LISTING INDIVIDUAL ANIMALS AFFEC NEOPLASTIC AND NON-NEOPLASTIC (90-DAY EXPOSURE EVALUATION INCLUDING EARLY DEATHS FROM THE REPRODUCTION EVAL LESIONS LYMPHATIC AND HEMATOPOIETIC SYSTEM BONE MARROW NO ABNORMALITY DETECTED . HYPERPLASIA, GRANULOCYTIC. ATROPHY. TREATMENT (mg/kg/day) LESION INCIDEN 0 25 II IV (10) (1) 643354 643361 643362 643374 643398 643406 643436 643463 643477 643486 643321 Figure in parentheses is number of animals microscopically examined for this tissue The absence of a number indicates the lesion specified was not identified 398 ^,^^.^'"-w"w H-24516: Subchronic Toxicity 90-Day Gavage Study in Rats with One-Generation Reproduction Evaluations TABLE 45 (CONTINUED) MICROSCOPIC OBSERVATIONS IN FEMALE RATS LISTING INDIVIDUAL ANIMALS AFF NEOPLASTIC AND NON-NEOPLASTIC (90-DAY EXPOSURE EVALUATION INCLUDING EARLY DEATHS FROM THE REPRODUCTION EV LESIONS ENDOCRINE SYSTEM PITUITARY GLAND NO ABNORMALITY DETECTED TREATMENT (mg/kg/day) LESION INCID 0 25 II IV (10) 643354 643361 643362 643374 643398 643406 643436 643463 643477 643486 (1) 643321 Figure in parentheses is number of animals microscopically examined for this tissue The absence of a number indicates the lesion specified was not identified 399 Company SanRIzed. Does not eontain H-24516: Subchronic Toxicity 90-Day Gavage Study in Rats with One-Generation Reproduction Evaluations TABLE 45 (CONTINUED) MICROSCOPIC OBSERVATIONS IN FEMALE RATS LISTING INDIVIDUAL ANIMALS AFF NEOPLASTIC AND NON-NEOPLASTIC (90-DAY EXPOSURE EVALUATION INCLUDING EARLY DEATHS FROM THE REPRODUCTION EVA LESION INCIDE LESIONS ENDOCRINE SYSTEM TREATMENT 0 25 (nig/kg/day) II IV THYROID GLAND NO ABNORMALITY DETECTED HYPERTROPHY, FOLLICULAR. (10) 643354 643361 643362 643374 643398 643406 643436 643463 643477 643486 (10) 643321 643364 643390 643396 ALTERATI ON, COLLOID. Figure in parentheses is number of animals microscopically examined for this tissue The absence of a number indicates the lesion specified was not identified 643324 643380 643389 643410 643433 643458 400 Company Sanitized. Does not contain H-24516: Subchronic Toxicity 90-Day Gavage Study in Rats with One-Generation Reproduction Evaluations TABLE 45 (CONTINUED) MICROSCOPIC OBSERVATIONS IN FEMALE RATS LISTING INDIVIDUAL ANIMALS AFF NEOPLASTIC AND NON-NEOPLASTIC (90-DAY EXPOSURE EVALUATION INCLUDING EARLY DEATHS FROM THE REPRODUCTION EVA LESIONS ENDOCRINE SYSTEM THYROID GLAND ALTERATION, COLLOID. PARATHYROID GLANDS NO ABNORMALITY DETECTED TREATMENT (mg/kg/day) LESION INCIDE 0 25 II IV (10) (10) (6) 643354 643362 643374 643406 643436 643463 (1) 643321 Figure in parentheses is number of animals microscopically examined for this tissue The absence of a number indicates the lesion specified was not identified 401 Company Sanitized. Does not con H-24516: Subchronic Toxicity 90-Day Gavage Study in Rats with One-Generation Reproduction Evaluations TABLE 45 (CONTINUED) MICROSCOPIC OBSERVATIONS IN FEMALE RATS LISTING INDIVIDUAL ANIMALS AFF NEOPLASTIC AND NON-NEOPLASTIC (90-DAY EXPOSURE EVALUATION INCLUDING EARLY DEATHS FROM THE REPRODUCTION EV LESIONS ENDOCRINE SYSTEM ADRENAL GLANDS NO ABNORMALITY DETECTED | LESION INCID TREATMENT 0 25 (mg/kg/day) II IV (10) 643354 643361 643362 643374 643398 643406 643436 643463 643477 643486 (1) 643321 Figure in parentheses is number of animals microscopically examined for this tissue The absence of a number indicates the lesion specified was not identified 402 Company SanHlzed. Does not h ^Ir H-24516; Subchronic Toxicity 90-Day Gavage Study in Rats with One-Generation Reproduction Evaluations TABLE 45 (CONTINUED) MICROSCOPIC OBSERVATIONS IN FEMALE RATS LISTING INDIVIDUAL ANIMALS AFF NEOPLASTIC AND NON-NEOPLASTIC (90-DAY EXPOSURE EVALUATION INCLUDING EARLY DEATHS FROM THE REPRODUCTION EVA LESIONS NERVOUS SYSTEM BRAIN NO ABNORMALITY DETECTED TREATMENT (nig/kg/day) LESION INCIDE 0 25 II IV (10) 643354 643361 643362 643374 643398 643406 643436 643463 643477 643486 (1) 643321 Figure in parentheses is number of animals microscopically examined for this tissue The absence of a number indicates the lesion specified was not identified 403 H-24516: Subchronic Toxicity 90-Day Gavage Study in Rats with One-Generation Reproduction Evaluations TABLE 45 (CONTINUED) MICROSCOPIC OBSERVATIONS IN FEMALE RATS LISTING INDIVIDUAL ANIMALS AFF NEOPLASTIC AND NON-NEOPLASTIC (90-DAY EXPOSURE EVALUATION INCLUDING EARLY DEATHS FROM THE REPRODUCTION EV LESIONS NERVOUS SYSTEM SPINAL CORD NO ABNORMALITY DETECTED TREATMENT (mg/kg/day) LESION INCIDE 0 25 II IV (10) 643354 643361 643362 643374 643398 643406 643436 643463 643477 643486 (1) 643321 Figure in parentheses is number of animals microscopically examined for this tissue The absence of a number indicates the lesion specified was not identified 404 ^tW Sanded. Do H-24516: Subchronic Toxicity 90-Day Gavage Study in Rats with One-Generation Reproduction Evaluations TABLE 45 (CONTINUED) MICROSCOPIC OBSERVATIONS IN FEMALE RATS LISTING INDIVIDUAL ANIMALS AF NEOPLASTIC AND NON-NEOPLASTIC (90-DAY EXPOSURE EVALUATION INCLUDING EARLY DEATHS FROM THE REPRODUCTION EV LESIONS NERVOUS SYSTEM SCIATIC NERVE NO ABNORMALITY DETECTED * TREATMENT (mg/kg/day) LESION INCID 0 25 II IV (10) 643354 643361 643362 643374 643398 643406 643436 643463 643477 643486 (1) 643321 Figure in parentheses is number of animals microscopically examined for this tissue The absence of a number indicates the lesion specified was not identified 405 Company SanRIzed. Does nol cont H-24516: Subchronic Toxicity 90-Day Gavage Study in Rats with One-Generation Reproduction Evaluations TABLE 45 (CONTINUED) MICROSCOPIC OBSERVATIONS IN FEMALE RATS LISTING INDIVIDUAL ANIMALS AF NEOPLASTIC AND NON-NEOPLASTIC (90-DAY EXPOSURE EVALUATION INCLUDING EARLY DEATHS FROM THE REPRODUCTION EV LESIONS MUSCULAR AND SKELETAL SYSTEM SKELETAL MUSCLE NO ABNORMALITY DETECTED TREATMENT (ing/kg/day) LESION IMCID 0 25 II IV (10) 643354 643361 643362 643374 643398 643406 643436 643463 643477 643486 (1) 64332 Figure in parentheses is number of animals microscopically examined for this tissue The absence of a number indicates the lesion specified was not identified 406 Company Sanitized. Does not co H-24516; Subchronic Toxicity 90-Day Gavage Study in Rats with One-Generation Reproduction Evaluations TABLE 45 (CONTINUED) MICROSCOPIC OBSERVATIONS IN FEMALE RATS LISTING INDIVIDUAL ANIMALS AFF NEOPLASTIC AND NON-NEOPLASTIC (90-DAY EXPOSURE EVALUATION INCLUDING EARLY DEATHS FROM THE REPRODUCTION EV LESIONS MUSCULAR AND SKELETAL SYSTEM FEMUR/KNEE JOINT NO ABNORMALITY DETECTED TREATMENT (mg/kg/day) LESION INCID 0 25 II IV (10) 643354 643361 643362 643374 643398 643406 643436 643463 643477 643486 (1) 643321 Figure in parentheses is number of animals microscopically examined for this tissue The absence of a number indicates the lesion specified was not identified 407 Company Sanitized. Does not con H-24516: Subchronic Toxicity 90-Day Gavage Study in Rats with One-Generation Reproduction Evaluations TABLE 45 (CONTINUED) MICROSCOPIC OBSERVATIONS IN FEMALE RATS LISTING INDIVIDUAL ANIMALS AFF NEOPLASTIC AND NON-NEOPLASTIC (90-DAY EXPOSURE EVALUATION INCLUDING EARLY DEATHS FROM THE REPRODUCTION EVA LESIONS MUSCULAR AND SKELETAL SYSTEM STERNUM NO ABNORMALITY DETECTED TREATMENT (mg/kg/day) LESION INCIDE 0 25 II IV (10) 643354 643361 643362 643374 643398 643406 643436 643463 643477 643486 (1) 643321 Figure in parentheses is number of animals microscopically examined for this tissue The absence of a number indicates the lesion specified was not identified 408 Company Sanitized. Does not c H-24516: Subchronic Toxicity 90-Day Gavage Study in Rats with One-Generation Reproduction Evaluations TABLE 45 (CONTINUED) MICROSCOPIC OBSERVATIONS IN FEMALE RATS LISTING INDIVIDUAL ANIMALS AFF NEOPLASTIC AND NON-NEOPLASTIC (90-DAY EXPOSURE EVALUATION INCLUDING EARLY DEATHS FROM THE REPRODUCTION EVA LESIONS MUSCULAR AND SKELETAL SYSTEM MANDIBLE NO ABNORMALITY DETECTED DEGENERATI ON, AMELOBLASTS. TREATMENT (mg/kg/day) LESION INCIDE 0 25 II IV (10) 643354 643361 643362 643374 643398 643406 643436 643463 643477 643486 (9) 643324 643364 643380 643389 643390 643396 643410 643433 643458 Figure in parentheses is number of animals microscopically examined for this tissue The absence of a number indicates the lesion specified was not identified 409 Company Sanitized. Does not c H-24516: Subchronic Toxicity 90-Day Gavage Study in Rats with One-Generation Reproduction Evaluations TABLE 45 (CONTINUED) MICROSCOPIC OBSERVATIONS IN FEMALE RATS LISTING INDIVIDUAL ANIMALS AFF NEOPLASTIC AND NON-NEOPLASTIC (90-DAY EXPOSURE EVALUATION INCLUDING EARLY DEATHS FROM THE REPRODUCTION EV LESIONS REPRODUCTIVE SYSTEM OVARIES NO ABNORMALITY DETECTED TREATMENT (mg/kg/day) LESION INCIDE 0 25 II IV (10) 643354 643361 643362 643374 643398 643406 643436 643463 643477 643486 (1) 643321 Figure in parentheses is number of animals microscopically examined for this tissue The absence of a number indicates the lesion specified was not identified 410 Santtlxed-D Company H-24516: Subchronic Toxicity 90-Day Gavage Study in Rats with One-Generation Reproduction Evaluations TABLE 45 (CONTINUED) MICROSCOPIC OBSERVATIONS IN FEMALE RATS LISTING INDIVIDUAL ANIMALS AFF NEOPLASTIC AND NON-NEOPLASTIC (90-DAY EXPOSURE EVALUATION INCLUDING EARLY DEATHS FROM THE REPRODUCTION EVA LESIONS REPRODUCTIVE SYSTEM UTERUS NO ABNORMALITY DETECTED DILATATION, LUMEN. TREATMENT (ing/kg/day) LESION INCIDE 0 25 II IV (10) 643354 643361 643362 643374 643398 643406 643436 643463 643477 643486 (1) 643321 Figure in parentheses is number of animals microscopically examined or this tissue The absence of a number indicates the lesion specified was not identified 411 Company Sanitized. Does not cont -' . '-e-/' H-24516: Subchronic Toxicity 90-Day Gavage Study in Rats with One-Generation Reproduction Evaluations TABLE 45 (CONTINUED) MICROSCOPIC OBSERVATIONS IN FEMALE RATS LISTING INDIVIDUAL ANIMALS AFF NEOPLASTIC AND NON-NEOPLASTIC (90-DAY EXPOSURE EVALUATION INCLUDING EARLY DEATHS FROM THE REPRODUCTION EVA LESIONS REPRODUCTIVE SYSTEM MAMMARY GLAND (FEMALE) NO ABNORMALITY DETECTED TREATMENT (nig/kg/day) LESION INCIDE 0 25 II IV (10) 643354 643361 643362 643374 643398 643406 643436 643463 643477 643486 (1) 643321 Figure in parentheses is number of animals microscopically examined for this tissue The absence of a number indicates the lesion specified was not identified 412 Company Sanitized. Does not conta H-24516: Subchronic Toxicity 90-Day Gavage Study in Rats with One-Generation Reproduction Evaluations TABLE 45 (CONTINUED) MICROSCOPIC OBSERVATIONS IN FEMALE RATS LISTING INDIVIDUAL ANIMALS AFF NEOPLASTIC AND NON-NEOPLASTIC (90-DAY EXPOSURE EVALUATION INCLUDING EARLY DEATHS FROM THE REPRODUCTION EV LESIONS CUTANEOUS SYSTEM SKIN NO ABNORMALITY DETECTED TREATMENT (ing/kg/day) LESION INCIDE 0 25 II IV (10) 643354 643361 643362 643374 643398 643406 643436 643463 643477 643486 (1) 643321 Figure in parentheses is number of animals microscopically examined for this tissue The absence of a number indicates the lesion specified was not identified 413 Company Sanitized. Does not conta H-24516: Subchronic Toxicity 90-Day Gavage Study in Rats with One-Generation Reproduction Evaluations TABLE 45 (CONTINUED) MICROSCOPIC OBSERVATIONS IN FEMALE RATS LISTING INDIVIDUAL ANIMALS AFF NEOPLASTIC AND NON-NEOPLASTIC (90-DAY EXPOSURE EVALUATION INCLUDING EARLY DEATHS FROM THE REPRODUCTION EVA LESIONS SPECIAL SENSES SYSTEM TREATMENT (mg/kg/day) LESION INCIDE 0 25 II IV EYE(S) WITH OPTIC NERVE NO ABNORMALITY DETECTED OPTIC NERVE NOT PRESENT. AUTOLYSIS: NECROPSY AND HISTOLOGY PERFORMED. (10) 643354 643361 643362 643374 643398 643406 643436 643463 643477 643486 (1) 643321 643463 643477 Figure in parentheses is number of animals microscopically examined for this tissue The absence of a number indicates the lesion specified was not identified 414 Company Sanitized. Does not co H-24516: Subchronic Toxicity 90-Day Gavage Study in Rats with One-Generation Reproduction Evaluations TABLE 45 (CONTINUED) MICROSCOPIC OBSERVATIONS IN FEMALE RATS LISTING INDIVIDUAL ANIMALS AFF NEOPLASTIC AND NON-NEOPLASTIC (90-DAY EXPOSURE EVALUATION INCLUDING EARLY DEATHS FROM THE REPRODUCTION EVA LESIONS DIGESTIVE SYSTEM | LESION INCIDE TREATMENT 0 50 (mg/kg/day) II IV PANCREAS NO ABNORMALITY DETECTED (10) 641240 641245 641249 641283 641293 641384 ATROPHY. 641257 641290 641335 641344 Figure in parentheses is number of animals microscopically examined for this tissue The absence of a number indicates the lesion specified was not identified 415 Company Sanitized. Does not co H-24516: Subchronic Toxicity 90-Day Gavage Study in Rats with One-Generation Reproduction Evaluations TABLE 45 (CONTINUED) MICROSCOPIC OBSERVATIONS IN FEMALE RATS LISTING INDIVIDUAL ANIMALS AFF NEOPLASTIC AND NON-NEOPLASTIC (ONE-MONTH RECOVERY EVALUATION) LESION INCIDE LESIONS DIGESTIVE SYSTEM LIVER NO ABNORMALITY DETECTED NECROSIS, FOCAL. INFLAMMATI ON, SUBACUTE/CHRONIC. TREATMENT (nig/kg/day) FATTY CHANGE, MEDIAN CLEFT. Figure in parentheses is number of animals microscopically examined for this tissue The absence of a number indicates the lesion specified was not identified 416 Company Sanitized. Does no H-24516: Subchronic Toxicity 90-Day Gavage Study in Rats with One-Generation Reproduction Evaluations TABLE 45 (CONTINUED) MICROSCOPIC OBSERVATIONS IN FEMALE RATS LISTING INDIVIDUAL ANIMALS AFF NEOPLASTIC AND NON-NEOPLASTIC (ONE-MONTH RECOVERY EVALUATION) LESION INCIDE LESIONS TREATMENT (mg/kg/day) DIGESTIVE SYSTEM PANCREAS NO ABNORMALITY DETECTED ESOPHAGUS NO ABNORMALITY DETECTED STOMACH NO ABNORMALITY DETECTED DUODENUM NO ABNORMALITY DETECTED JEJUNUM NO ABNORMALITY DETECTED Figure in parentheses is number of animals microscopically examined for this tissue The absence of a number indicates the lesion specified was not identified 417 Company Sanitized. Does not co %y H-24516: Subchronic Toxicity 90-Day Gavage Study in Rats with One-Generation Reproduction Evaluations TABLE 45 (CONTINUED) MICROSCOPIC OBSERVATIONS IN FEMALE RATS LISTING INDIVIDUAL ANIMALS AFFE NEOPLASTIC AND NON-NEOPLASTIC (ONE-MONTH RECOVERY EVALUATION) LESION INCIDE LESIONS TREATMENT (nig/kg/day) DIGESTIVE SYSTEM ILEUM NO ABNORMALITY DETECTED CECUM NO ABNORMALITY DETECTED COLON NO ABNORMALITY DETECTED RECTUM NO ABNORMALITY DETECTED SALIVARY GLANDS NO ABNORMALITY DETECTED Figure in parentheses is number of animals microscopically examined for this tissue The absence of a number indicates the lesion specified was not identified 418 ""-XT s D. ,, ^ w H-24516: Subchronic Toxicity 90-Day Gavage Study in Rats with One-Generation Reproduction Evaluations TABLE 45 (CONTINUED) MICROSCOPIC OBSERVATIONS IN FEMALE RATS LISTING INDIVIDUAL ANIMALS AFFE NEOPLASTIC AND NON-NEOPLASTIC (ONE-MONTH RECOVERY EVALUATION) LESION INCIDE; LESIONS URINARY SYSTEM KIDNEYS NO ABNORMALITY DETECTED TREATMENT (mg/kg/day) NEPHROPATHY, CHRONIC PROGRESSIVE. NECROSIS, TUBULAR. MINERALIZATION. INFLAMMATION, ACUTE. HYPERPLASIA, TRANSITIONAL CELL. HYDRONEPHROSIS, BILATERAL. CYST. Figure in parentheses is number of animals microscopically examined for this tissue The absence of a number indicates the lesion specified was not identified 419 Company Sanitized. Does not co H-24516: Subchronic Toxicity 90-Day Gavage Study in Rats with One-Generation Reproduction Evaluations TABLE 45 (CONTINUED) MICROSCOPIC OBSERVATIONS IN FEMALE RATS LISTING INDIVIDUAL ANIMALS AFF NEOPLASTIC AND NON-NEOPLASTIC (ONE-MONTH RECOVERY EVALUATION) LESION INCIDi LESIONS TREATMENT (mg/kg/day) URINARY SYSTEM URINARY BLADDER INFLAMMATION, SUBACUTE/CHRONIC. HYPERPLASIA, SIMPLE, TRANSITIONAL HEMORRHAGE. CELL. Figure in parentheses is number of animals microscopically examined for this tissue The absence of a number indicates the lesion specified was not identified 420 Comiwny Sanfflzed. Does not w H-24516: Subchronic Toxicity 90-Day Gavage Study in Rats with One-Generation Reproduction Evaluations TABLE 45 (CONTINUED) MICROSCOPIC OBSERVATIONS IN FEMALE RATS LISTING INDIVIDUAL ANIMALS AFF NEOPLASTIC AND NON-NEOPLASTIC (ONE-MONTH RECOVERY EVALUATION) LESION IMCIDE LESIONS TREATMENT (mg/kg/day) RESPIRATORY SYSTEM LUNGS NO ABNORMALITY DETECTED TRACHEA - NO ABNORMALITY DETECTED PHARYNX/LARYNX NO ABNORMALITY DETECTED Figure in parentheses is number of animals microscopically examined for this tissue The absence of a number indicates the lesion specified was not identified 421 Company Sanitized. Does not con H-24516: Subchronic Toxicity 90-Day Gavage Study in Rats with One-Generation Reproduction Evaluations TABLE 45 (CONTINUED) MICROSCOPIC OBSERVATIONS IN FEMALE RATS LISTING INDIVIDUAL ANIMALS AFFE NEOPLASTIC AND NON-NEOPLASTIC (ONE-MONTH RECOVERY EVALUATION) LESION INCIDEN LESIONS RESPIRATORY SYSTEM NOSE NO ABNORMALITY DETECTED TREATMENT (mg/kg/day) SQUAMOUS HYPERPLASIA, NASOLACRIMAL DUCT. INFLAMMATION, SUBACUTE/CHRONIC, NASOLACRIMAL DUCT. DEGENERATION, AMELOBLASTS. Figure in parentheses is number of animals microscopically examined for this tissue The absence of a number indicates the lesion specified was not identified 422 CompanySanRfced. Does not c H-24516: Subchronic Toxicity 90-Day Gavage Study in Rats with One-Generation Reproduction Evaluations TABLE 45 (CONTINUED) MICROSCOPIC OBSERVATIONS IN FEMALE RATS LISTING INDIVIDUAL ANIMALS AFFE NEOPLASTIC AND NON-NEOPLASTIC (ONE-MONTH RECOVERY EVALUATION) LESION INCIDE^ LESIONS TREATMENT (mg/kg/day) CARDIOVASCULAR SYSTEM HEART NO ABNORMALITY DETECTED AORTA NO ABNORMALITY DETECTED Figure in parentheses is number of animals microscopically examined for this tissue The absence of a number indicates the lesion specified was not identified 423 Company SanMzed. Does n H-24516: Subchronic Toxicity 90-Day Gavage Study in Rats with One-Generation Reproduction Evaluations TABLE 45 (CONTINUED) MICROSCOPIC OBSERVATIONS IN FEMALE RATS LISTING INDIVIDUAL ANIMALS AFFE NEOPLASTIC AND NON-NEOPLASTIC (ONE-MONTH RECOVERY EVALUATION) LESION INCIDEN LESIONS TREATMENT (mg/kg/day) LYMPHATIC AND HEMATOPOIETIC SYSTEM SPLEEN NO ABNORMALITY DETECTED THYMUS ATROPHY. MANDIBULAR LYMPH NODE NO ABNORMALITY DETECTED MESENTERIC LYMPH NODE NO ABNORMALITY DETECTED BONE MARROW HYPERPLASIA, GRANULOCYTIC. Figure in parentheses is number of animals microscopically examined for this tissue The absence of a number indicates the lesion specified was not identified 424 Company Sanitized. Does not cont H-24516: Subchronic Toxicity 90-Day Gavage Study in Rats with One-Generation Reproduction Evaluations TABLE 45 (CONTINUED) MICROSCOPIC OBSERVATIONS IN FEMALE RATS LISTING INDIVIDUAL ANIMALS AFF NEOPLASTIC AND NON-NEOPLASTIC (ONE-MONTH RECOVERY EVALUATION) LESION INCIDH LESIONS ENDOCRINE SYSTEM PITUITARY GLAND NO ABNORMALITY DETECTED HYPERPLASIA, DIFFUSE. THYROID GLAND NO ABNORMALITY DETECTED TREATMENT (mg/k9/day) ALTERATI ON, COLLOID. Figure in parentheses is number of animals microscopically examined for this tissue The absence of a number indicates the lesion specified was not identified 425 CompanySanitized. Does not conta H-24516: Subchronic Toxicity 90-Day Gavage Study in Rats with One-Generation Reproduction Evaluations TABLE 45 (CONTINUED) MICROSCOPIC OBSERVATIONS IN FEMALE RATS LISTING INDIVIDUAL ANIMALS AFFE NEOPLASTIC AND NON-NEOPLASTIC (ONE-MONTH RECOVERY EVALUATION) LESION INCIDEN LESIONS TREATMENT (mg/kg/day) ENDOCRINE SYSTEM PARATHYROID GLANDS NO ABNORMALITY DETECTED ADRENAL GLANDS NO ABNORMALITY DETECTED Figure in parentheses is number of animals microscopically examined for this tissue The absence of a number indicates the lesion specified was not identified 426 Company SanHlzed. Does not cont H-24516: Subchronic Toxicity 90-Day Gavage Study in Rats with One-Generation Reproduction Evaluations TABLE 45 (CONTINUED) MICROSCOPIC OBSERVATIONS IN FEMALE RATS LISTING INDIVIDUAL ANIMALS AFF NEOPLASTIC AND NON-NEOPLASTIC (ONE-MONTH RECOVERY EVALUATION) LESION INCIDE LESIONS TREATMENT (ing/kg/day) NERVOUS SYSTEM BRAIN NO ABNORMALITY DETECTED SPINAL CORD . NO ABNORMALITY DETECTED SCIATIC NERVE NO ABNORMALITY DETECTED Figure in parentheses is number of animals microscopically examined for this tissue The absence of a number indicates the lesion specified was not identified 427 Conwny Sanitized. Does no! contain T H-24516: Subchronic Toxicity 90-Day Gavage Study in Rats with One-Generation Reproduction Evaluations TABLE 45 (CONTINUED) MICROSCOPIC OBSERVATIONS IN FEMALE RATS LISTING INDIVIDUAL ANIMALS AFFE NEOPLASTIC AND NON-NEOPLASTIC (ONE-MONTH RECOVERY EVALUATION) LESION INCIDE LESIONS MUSCULAR AND SKELETAL SYSTEM SKELETAL MUSCLE NO ABNORMALITY DETECTED FEMUR/KNEE JOINT NO ABNORMALITY DETECTED STERNUM NO ABNORMALITY DETECTED MANDIBLE NO ABNORMALITY DETECTED TREATMENT (nig/kg/day) Figure in parentheses is number of animals microscopically examined for this tissue The absence of a number indicates the lesion specified was not identified 428 Company Sanitized. Does not contain H-24516: Subchronic Toxicity 90-Day Gavage Study in Rats with One-Generation Reproduction Evaluations TABLE 45 (CONTINUED) MICROSCOPIC OBSERVATIONS IN FEMALE RATS LISTING INDIVIDUAL ANIMALS AFFE NEOPLASTIC AND NON-NEOPLASTIC (ONE-MONTH RECOVERY EVALUATION) LESION INCIDE LESIONS TREATMENT (mg/kg/day) REPRODUCTIVE SYSTEM OVARIES NO ABNORMALITY DETECTED UTERUS - NO ABNORMALITY DETECTED MAMMARY GLAND (FEMALE) NO ABNORMALITY DETECTED Figure in parentheses is number of animals microscopically examined for this tissue The absence of a number indicates the lesion specified was not identified 429 Company Sanitized. Does not con Ah 'sSI" . H-24516: Subchronic Toxicity 90-Day Gavage Study in Rats with One-Generation Reproduction Evaluations TABLE 45 (CONTINUED) MICROSCOPIC OBSERVATIONS IN FEMALE RATS LISTING INDIVIDUAL ANIMALS AFFE NEOPLASTIC AND NON-NEOPLASTIC (ONE-MONTH RECOVERY EVALUATION) LESION INCIDE^N LESIONS TREATMENT (mg/kg/day) CUTANEOUS SYSTEM SKIN NO ABNORMALITY DETECTED Figure in parentheses is number of animals microscopically examined for this tissue The absence of a number indicates the lesion specified was not identified 430 Company Sanitized. Does not contain H-24516: Subchronic Toxicity 90-Day Gavage Study in Rats with One-Generation Reproduction Evaluations TABLE 45 (CONTINUED) MICROSCOPIC OBSERVATIONS IN FEMALE RATS LISTING INDIVIDUAL ANIMALS AFFE NEOPLASTIC AND NON-NEOPLASTIC (ONE-MONTH RECOVERY EVALUATION) LESION INCIDEN LESIONS TREATMENT (nig/kg/day) SPECIAL SENSES SYSTEM EYE(S) WITH OPTIC NERVE NO ABNORMALITY DETECTED Figure in parentheses is number of animals microscopically examined for this tissue The absence of a number indicates the lesion specified was not identified 431 Company Sanitized. Does not contain TS H-24516: Subchronic Toxicity 90-Day Gavage Study in Rats with One-Generation Reproduction Evaluations TABLE 45 (CONTINUED) MICROSCOPIC OBSERVATIONS IN FEMALE RATS LISTING INDIVIDUAL ANIMALS AFFE NEOPLASTIC AND NON-NEOPLASTIC (THREE-MONTH RECOVERY EVALUATION) LESIONS RESPIRATORY SYSTEM NOSE NO ABNORMALITY DETECTED INFLAMMATION, SUBACUTE/CHRONIC. HYPERPLASIA/SQUAMOUS METAPLASIA, TRANSITIONAL CELL. DEGENERATION, AMELOBLASTS. | LESION INCIDE TREATMENT 0 25 (mg/kg/day) II IV (5) 643384 643402 643383 643465 643484 643383 643465 643484 Figure in parentheses is number of animals microscopically examined for this tissue The absence of a number indicates the lesion specified was not identified 432 CompanySanitized. Does not contain H-24516: Subchronic Toxicity 90-Day Gavage Study in Rats with One-Generation Reproduction Evaluations TABLE 45 (CONTINUED) MICROSCOPIC OBSERVATIONS IN FEMALE RATS LISTING INDIVIDUAL ANIMALS AFF NEOPLASTIC AND NON-NEOPLASTIC (THREE-MONTH RECOVERY EVALUATION) LESIONS ENDOCRINE SYSTEM THYROID GLAND NO ABNORMALITY DETECTED ALTERATION, COLLOID. TREATMENT (nig/kg/day) LESION INCIDE 0 25 II IV (5) (4) 643383 643384 643402 643465 643484 643379 643391 643437 643483 Figure in parentheses is number of animals microscopically examined for this tissue The absence of a number indicates the lesion specified was not identified 433 Company Sanitized. Does not contain H-24516: Subchronic Toxicity 90-Day Gavage Study in Rats with One-Generation Reproduction Evaluations DuPont-5368 TABLE 46 MEAN BODY WEIGHTS AND MEAN BODY WEIGHT GAINS OF Pi MALE RATS GROUP DOSE (nig/kg/day) N TEST DAY 78 85 92 99 106 II I--0 1-0i V-0 VI I-C1 ( ) 25 100 2 50 2 0 i0 20 L9 MEAN BC>DY WEIGHT (gran>s) 555 .6 (62 .6)3 569 .5 (63 .3) 583 .4 (64 .4) 595 .7 (63 .2) 607 .6 (64 .7) 543 .9 (52 .9) 555 .3 (54 .7) 568 .8 (56 .5) 582 .2 (58 .0) 590 .5 (62 .5) 547 .5(36 .3) 559 .3(39 .0) 569 .5(40 .7) 579 .1(45 .6) 574 .2(52 .3) 495 .0 (48 .1)* 516 .1 (47 .0) * 531 .1 (51 .7)* 539 .0 (59 .8)* 547 .2 (65 .3)* GR.OUP I -C1 III-C) V-0 VII-C) D(3SE 0 25 100 250 (mg/k;g/day) N 20 20 20 19 T]3ST DJ\YS MEAN BODY WEIGIIT GA:IN (grams) 78 -85 85 -92 92 -99 99 -106 13 .9 (6 .Da 13 .9 (6 .7) 12 .3 (5 .5) 12 .0 (5 .0) 11 .4(8. 5) 13 .5(5. 8) 13 .4(6. 4) 8 .4(7. 5) 11 .7(7. 3) 10 .2(8. 0) 9 .7(10 .3) -5 .0 (21 .7)* 21 .2(11 .3) 14 .9(8. 4) 7 .9(15 .2) 8 .3(8. 9)* 78 -106 52 .0 (7 .1) 46 .7(16 .5) 26 .6(30 .1) a Standard deviation is reported in parentheses. 52 .2(32 .7) * Statistically significant difference from control by Jonckheere-Terpstra test (p < 0.05). 434 Company Sanitized. Does not contain TSCA CBI H-24516: Subchronic Toxicity 90-Day Gavage Study in Rats with One-Generation Reproduction Evaluations DuPont-5368 TABLE 47 MEAN BODY WEIGHTS AND MEAN BODY WEIGHT GAINS OF Pi FEMALE RATS DURING GESTATION GROUP DOSE (mg/kg/day) N GESTATION DAY 0 7 14 21 I 1-0 0 13 IV-0 25 16 VI-0 100 15 V III-'0 250 14 305. 7 (31 .8)3 333. 9 (33 .3) 367. 0 (35 .1) 453. 2 (39 .0)C MEAN BOCY WE:IGHT (granIS) 315 .2(23 .3) 344 .4(28 .1) 370 .0(22 .4) 454 .9(55 .4)d 302 .1(18 .5) 333 .4 (17 .1) 366 .0(19 .2) 432 .7(40 .0)d 300. 3 (22 .0) 329. 2(28 .6) 367. 2 (22 .0)^ 444. 5(35 5)d GROUP DOSE (mg/kg/day) N I 1-0 0 13 r V-0 25 16 V 1-0 3LOO 15 VIII- 0 250 14 GESTATION DAYS MEAN BIODY WEIGH[T GA:IN (g rams) 0-7 7-14 14-21 28 .2 (6. 0)a 33 .1 (5. 4) 86 .5 (16 .l)c 29 .2 (8. 8) 25 .5 (14 .2) 82 .4 (44 5)d 31 .3 (6. 9) 32 .5 (5. 0) 71 .9 (28 -3)d 28.9(23 .0) 32.9 (6. 1)^ 82.0 (33 .5}b 0-21 146 .1 (19 .3)'= 135 .8 (45 .7)d 135 .1 (29 .7)d a Standard deviation is reported in parentheses. Jb N = 13. c N = 10. d N = 11. 146.2(34 6)d There were no statistically significant differences from control by Jonckheere-Terpstra test (p < 0.05). 435 ^Pany sanded. Does not cointahl TSCA CBI H-24516: Subchronic Toxicity 90-Day Gavage Study in Rats with One-Generation Reproduction Evaluations DuPont-5368 TABLE 48 MEAN BODY WEIGHTS AND MEAN BODY WEIGHT GAINS OF Pi FEMALE RATS DURING LACTATION GROUP DOSE (mg/kg/day) N LACTATION DAY 0 7 14 21 II-O 0 13 IV-0 25 17 VI-0 100 14 345.5(36 .2)3 346.9(31 .0) 360.6(33 .4) 351.2 (30 .6) MEAN BODY WEIGHT (grams) 351.6(29.8) 351.3(30.7) 380.9(18.9) 365.9(18.4) 337.2(32.9) 350.0(21.0) 371.4(18.1) 360.4(14.8) VIII- 0 250 13 341.7(21 .2) 349.3(25 .3) 362 .7(28 .9) 341.1(41 .2) GR.OUP D(3SE (mg/kg/day) N II-O 0 13 IV-0 25 17 V:1-0 1 00 14 VI:11- 0 2 50 L3 LACTATION Dl^YS MEAN BODY WEIGHT GAIN (9:rams) 0 -7 7 -14 14-21 1. 4 (22 I)3 13. 7(20 .7) -9. 4 (10 .9) -0. 3 (22 .6) 29. 6(19 .7) 15. 0 (14 .2) 12.8 (27 .7) 21.4 (11 .2) 11.1 (13 .1) 7.6 (17 .0) 13.3 (29 .9) -21.5 (43 .5) 0-21 5. 7 (20 .8) 14. 2 (21 .3) 23.1 (28 .5) a Stanclard deviation is reported in parentheses. -0.6 (38 .4) * Statistically significant differences from control by Jonckheere-Terpstra test (p < 0.05) . 436 Company Sanitized. Does not contain TSCA CBt H-24516: Subchronic Toxicity 90-Day Gavage Study in Rats with One-Generation Reproduction Evaluations DuPont-5368 TABLE 49 MEAN DAILY FOOD CONSUMPTION AND MEAN FOOD EFFICIENCY OF Pi FEMALE RATS DURING GESTATION GF3UP DIOSE (mg/h-g/da;7) N I 1-01 0 13 I V- 0 25 16 VI- 0 10() 15 VIII -0 25C) 14 GES1'ATI 01'I D;Mrs MK\N DAI:L Y FOOD C'ONSUMPTION (graims) 0 -7 7 -14 14 -21 24 .8 (3. 9)3 29 .5 (3. 7) 26 .1 (5. 7) 25. 2 (2 .9) 26. 6 (3 .2) 27. 2 (3 .4) 25 .8(2 .1) 28 .4(1 .9) 27 .0(3 .1) 26.8(4 .5) 29.2(3 .1) 26.5(4 5)b 0-21 26 .8 (3. 6) 26. 4 (2 .7) 27 .1(1 .8) a Stan.dard deviation is reported in parenthisses. h N = 13. 27.6(2 .5)b There were no statistically significant differences from control by Jonckheere-Terpstra test (p < 0.05). GROUP DOSE (mg/kg/day) N II-O 0 13 IV-0 25 16 VI-0 100 15 VIII-0 250 14 GESTATION DAYS MEAN FOOD EFFICIENCY (grams weight gain/grams food consumed) 0-7 7-14 14-21 0 .167 (.046)a 0 .162 (.028) 0 .553 (.312) 0 .163 (.039) 0 .141 (.072) 0 .365 (.238) 0 .172 (.031) 0 .163 (.022) 0 .395 (.178) 0 .134( .172) 0 .165( .032) 0 .440 ( .206)^ 0-21 0.268 (.053) 0.224(.088) 0.241(.057) a Standard deviation is reported in parentheses. b N = 13. 0.254(.056)^ There were no statistically significant differences from control by One-Way Analysis of Variance (p < 0.05). 437 H-24516: Subchronic Toxicity 90-Day Gavage Study in Rats with One-Generation Reproduction Evaluations____________DuPont-5368 TABLE 50 SUMMARY OF CLINICAL OBSERVATIONS IN Pi RATS PI MALE RATS DOSE GROUP (mg/kg/day) N Number of Rats with Observation 1-0 III-O V-0 VII-0 0 25 100 250 20 20 20 19 OBSERVATIONS Alopecia Colored Discharge Colored Discharge Teeth Clipped 10 0020 21 Teeth Crooked Eye(s) Nose 0 0 0 5* 1 Total No. of Rats with Masses_____________0______0______0______0_ 0 0 0 1 Statistically significant trend by Cochran-Armitage test; p < 0.05. 438 Does not contain TSCACBf H-24516: Subchronic Toxicity 90-Day Gavage Study in Rats with One-Generation Reproduction Evaluations____________DuPont-5368 TABLE 50 (CONTINUED) SUMMARY OF CLINICAL OBSERVATIONS IN PI RATS PI FEMALE RATS DURING GESTATION DOSE GROUP (mg/kg/day) N Number of Rats with Observation II-O IV-0 VI-0 VIII-0 0 25 100 250 18 19 19 17 OBSERVATIONS Alopecia Diarrhea Sore Stained Abdomen Stained Face Stained Perineum Teeth Clipped Weak Wet Perineum Wet Underbody Total No. of Rats Note: This table 010001 01000 021010 12011 with Masses_____________0______0______0______0 0 0 0 1 includes clinical observations from pregnant animals only. PI FEMALE RATS DURING LACTATION DOSE GROUP (mg/kg/day) N Number of Rats with Observation II-O IV-0 VI-0 VIII-0 0 25 100 250 13 17 14 14 OBSERVATIONS Abnormal Gait or Mobility Alopecia Colored Discharge Nose Discharge Vaginal Opening 10013004110 Hunched Over Teeth Clipped 0 0 1 0 Total No. of Rats with Masses______________0_______0_______0_______0 0 1 There were no statistically significant trends by Cochran-Armitage test; p < 0.05. 439 Company SanWzed. Does not contain TBCA CW H-24516: Subchronic Toxicity 90-Day Gavage Study in Rats with One-Generation Reproduction Evaluations DuPont-5368 TABLE 51 MEAN ESTROUS CYCLE PARAMETERS AND PRECOITAL INTERVAL IN Pi FEMALE RATS Percent Percent Percent of Days of Days of Days Mearl Cycl.e Dose GroiIP (mg/kg/day) N in in in Estrus Diestrus Proestrus Length (clays) II- 0 0 20 29 60 11 IV-0 25 19 22 65 13 VI- 0 100 20 25 63 12 VIII -0 a Standard jb N=19 c N=18 d N=17 250 18 deviation is 20 presented 69 12 in parentheses. 4.7(1 .54)3 ,b 4.5(0 .81) 4.6(0 .73)^ 4.7(1 .35) There were no significant trends (Jonckheere's test); p < 0.05. Mean Precoital Interval (days) 3 .8(2.46)C 3 .3(2.86) 2 .5(1.31)^ 3 .6 (2 .2.1}^ 440 CompanySanitized. Doe* not contain TSCA CBf H-24516: Subchronic Toxicity 90-Day Gavage Study in Rats with One-Generation Reproduction Evaluations____________DuPont-5368 TABLE 52 SUMMARY OF SPERM PARAMETERS IN Pi MALE RATS Group 1-0 III-O V-0 VII-0 Dose (mg/kg/day)_____0__________25___________100___________250 MOTILITY Percent Motile S.D. 93.3 3.6(10)a 92.2 5.8(10) 93.3 4.0(10) 90.3 6.1(10) MORPHOLOGY Percent Normal S.D. 98.8 0.8(10) 99.0 1.1(10) 99.2 0.7(10) 98.9 1.1(10) EPIDIDYMAL SPERM (Millions) Per Cauda 298.7 S.D. 32.3(10) 279.8 39.8(10) 278.0 44.9(10) 299.2 66.9(10) Per gram Cauda S.D. 1030.9 171.6(10) 998.3 144.3(10) 949.8 178.4(10) 945.7 150.5(10) TESTICULAR SPERMATIDS Per Testis S.D. (Millions) 130.1 17.1(10) 121.8 13.6(10) 159.9* 10.3(10) 146.5* 17.3(10) Per gram Testis S.D. 84.5 12.3(10) 84.5 12.0(10) 101.1* 9.1(10) 93.2* 9.5(10) a Number in group is in parentheses. * Statistically significant trend by Jonckheere-Terpstra test; p <_0.05. 441 Company Sanitized. Does not contain TSCA CBI H-24516: Subchronic Toxicity 90-Day Gavage Study in Rats with One-Generation Reproduction Evaluations DuPont-5368 TABLE 53 SUMMARY OF REPRODUCTIVE INDICES: Pi GENERATION MAl'ERNAL GROUP DOSE (mg/kg/day) II-O 0 MATING INDEX (%) (tt copulated/cohoused) 90.0 (18/20) FERTILITY INDEX (%) (# delivered/copulated) 72.2 (13/18) GESTATION LENGTH (days) 22.3 Number of Implantation Sites per pregnant female 14.0 (4.53)a Implantation Efficiency (^ 96.6 (3.33) IV-0 25 100.0 (20/20) 85.0 (17/20) 22.2 13.4 (4.58) 90.5 (13.47) VI-0 100 95.0 (19/20) 73.7 (14/19) 22.4 13.9 (2.95) 83.4* (16.16) VIII-0 250 94.7 (18/19) 77.8 (14/18) 22.4 14.1 (2.93) 84.5* (19.10) a Standard deviation is reported in parentheses. b Number of pups born/number of implantation sites X 100. There were no statistically significant trends in mating or fertility indices by Cochran-Armitage test; p < 0.05. There was no statistically significant difference from control in gestation length by One-Way Analysis of Variance; p < 0.05. * Statistically significant trend by Jonckheere's test; p < 0.05. 442 Company Sanitized. Does not contain TSCA CBI H-24516: Subchronic Toxicity 90-Day Gavage Study in Rats with One-Generation Reproduction Evaluations DuPont-5368 TABLE 54 MEAN PUP NUMBERS AND SURVIVAL: Fi GENERATION MATERNAL GROUP DOSE (mg/kg/day) N 11-0 0 13 IV-0 25 17 VI-0 100 14 VIII-0 250 13 Born Born Alive Day 4 Preculling Day 4 Postculling Day 7 Day 14 Day 21 MEAN NUMBER OF PUPS/LITTER 14.7 14.6 14.6 8.0 8.0 8.0 8.0 13.4 13.2 12.9 7.6 7.6 7.6 7.6 12.4 11.3 10.0* 6.3 6.3 6.3 6.3 12.5* 12.1* 11.8* 7.5 7.4 7.4 7.4 Born Born Alive Day 4 Preculling Day 4 Postculling Day 7 Day 14 Day 21 MEAN NUMBER OF MALE PUPS/LITTER 8.7 7.2 5.9 7.1 8.6 7.1 5.4 6.7 8.6 7.1 4.7 6.5 4.2 3.6 3.3 3.6 4.2 3.6 3.3 3.9 4.2 3.6 3.3 3.6 4.2 3.6 3.3 3.6 Born Born Alive Day 4 Preculling Day 4 Postculling Day 7 Day 14 Day 21 MEAN NUMBER OF FEMALE PUPS/LITTER 6.0 6.1 6.5 5.5 6.0 6.1 5.9 5.4 6.0 5.8 5.3 5.3 3.8 4.0 3.0 3.8 3.8 4.0 3.0 3.8 3.8 4.0 3.0 3.8 3.8 4.0 3 .0 3.8 SURVIVAL (t) Sex Ratio (males) 0.59 Gestation IndexS Mean % Born Alive 0-4 Day Viability 100.0 99.5 100.0 Lactation Index-b 100.0 Litter Survival0 100.0 a Percent litters delivered having at least one live pup. b Mean percent survival from day 4 postculling to day 21. c Percent litters born with at least one pup alive on day 0.50 100.0 99.2 97.6 100.0 100.0 21. 0.50 92.9 88.4 90.6 100.0 92.3 0.56 100.0 92.4 97.3 92.3 92.3 * Statistically significant trend by Jonckheere-Terpstra test; p < 0.05. Statistics were performed on combined pups per litter only. Male and female data are presented for information only. 443 Company SanHIzed. Does not contain TSCA CBI H-24516: Subchronic Toxicity 90-Day Gavage Study in Rats with One-Generation Reproduction Evaluations DuPont-5368 TAE(LE55 M;BAN PUP WEICjHTS: FiGENERATION MATERNAL iGROUP DOSE (mg/kg /day) N Day 0 Day 4 Preculling Day 4 Postculling Day 7 Day 14 Day 21 II-i0 0 13 IV-0 25 17 VI-0 100 13 M]3AN PUP WE:[GHTS (grams) 6.9 11.3 11.4 18.3 37.9 60.9 (0 .7)3 (1 .5) (1 .6) (1 .9) (3 .4) (6 .9) 6.7 11.4 11.4 18.0 37.0 60.3 (0.6) (1.6) (1.7) (2.2) (3.0) (5.5) 6 .8 11 .9 11 .9 18 .3 36 .1 58 .3 (0.7)^ (1.8) (1.9) (2.4) (3.2) (4.3) VIII- 0 250 13 6.4 10.1 10.1 15.5 29.5 45.4 (0 .6) (1 .7)* (1 .7)* (2 .1)* (3 .4)* (7 .7)* MEAN MALE PUP WEIGHTS (grams) Day 0 Day 4 Preculling Day 4 Postculling Day 7 Day 14 Day 21 7.0 11.6 11.7 18.8 38.7 62.5 (0 .7) (1 .5) (1 .5) (2 .0) (3 .6) (7 .4) 6.9 11.5 11.5 18.2 37.7 61.7 (0.7) f (1.7) (1.7) (2.3) (3.2) (6.2) 6 .9 12 .3 12 .3 18 .9 37 .1 60 .2 (0.8)^ (1.9) (2.0) (2.3) (3.1) (4.3) 6.7 10.7 10.8 15.7 29.6 45.7 (0 .5) (0 .8) (0 .7) (2 .3) (3 .8) (7 .7) MEAN FEMALE PUP WEIGHTS (grams) Day 0 Day 4 Preculling Day 4 Postculling Day 7 Day 14 Day 21 6.6 10.9 11.0 17.6 37.0 59.1 (0 .7) (1 .5) (1 .6) (1 .9) (3 .2) (6 .3) 6.5 (0.6) c 11.1 (1.8) 11.2 (1.8) 17.6 (2.2) 36.5 (3.0) 59.0 (5.5) a Standard deviation is reported in parentheses. b N = 12. c N = 14. 6 .5 11 .5 11 .4 17 .5 35 .0 56 .0 (O^)2' (1.7) (1.9) (2.7) (3.6) (4.7) 6.2 9.8 9.9 15.3 29.3 45.0 (0 .6) (1 .7) (1 .8) (2 .0) (3 .1) (8 .0) * Statistically significant trends by linea'r contrast of least square means; p < 0.05. Note: Statistical analyses were conducted on the combined pup weights. female data are presented for information only. Male and 444 Company Sanitized. Does not contain TSCA CBI H-24516: Subchronic Toxicity 90-Day Gavage Study in Rats with One-Generation Reproduction Evaluations____________DuPont-5368 TABLE 56 SUMMARY OF PUP CLINICAL OBSERVATIONS: Fi GENERATION MATERNAL GROUP DOSE (mg/kg/day) II-O 0 IV-0 25 VI-0 100 VIII-0 250 OBSERVATIONS Discharge Nose Weak 2(1)l)a 0 0 0 3 ( 0 0 0 0 0 0 51 TOTAL NUMBER OP OBSERVATIONS NUMBER OF LITTERS AFFECTED TOTAL NUMBER OF LITTERS____________________13______17______13______13 a Numbers outside the parentheses are the number of pups affected; the numbers in parentheses are the number of litters affected. There were no statistically significant trends by Cochran-Armitage test; p < 0.05. 445 Company Sanitized. Does not conta'n TSCA CBI H-24516; Subchronic Toxicity 90-Day Gavage Study in Rats with One-Generation Reproduction Evaluations DuPont-5368 TABLE 57 MEAN BODY WEIGHTS AND MEAN BODY WEIGHT GAINS OF F, MALE RATS GROUP DOSE (mg/kg/day) N DAYS ON TEST3 1 8 15 22 29 36 1-1 0 13 63.3(7.5)^ 108.7(12.8) 172.2 (18.0) 236.3(21.9) 294.7 (31.0) 333.4(33.5) III-1 V-1 25 100 16 12 MEAN BODY WEIGHT (grams) 62.5(7.0) 103.9(10.3) 163.9(15.3) 224.0(16.9) 278.7(23.6) 331.8(31.3)C 58.6(5.6) 100.5(8.9) 161.3 (13.0) 223.0(11.5) 279.2 (20.4) 310.5(35.5) VII-1 250 12 47.0(5.3)* 88.0(6.8)* 144.5(11.6)* 206.0(11.4)* 264.0(28.4)* 310.2(40.2)* III-] GROUP 1-1 V-1 D()SE 0 25 100 (mg/k g/day) N 13 16 12 DAY S ON TE sra MEAN BODY WEIGK[T GA:IN (g:rams) 1 -8 8 -15 15-22 22-29 29-36 45 .3(6. 4)& 63 .5(6. 8) 64 .1(7. 0) 58 .4 (13 .8) 38 .7(31 .8) 41 .5(5. 0) 60 .0(6. 0) 60 .1(5. 5) 54 .7 (16 .5) 54 .6(20 I)0 41 .9(4. 4) 60 .8(5. 2) 61 .7(5. 0) 56 .3(15 .6) 31 .2(19 .3) 1-36 270 .1 (30 .2) 269 .7(28 .9)0 251 .9(33 .3) a Day of Weaning = Test Day 1. Jb Standard deviation is reported in parentheses. c N = 15. VII-3 250 12 41 .0(7. 4) 56 .5(6. 7)* 61 .5(5. 7) 58 .0(22 .5) 46 .1 (25 .5) 263 .2(42 .3) Statistically significant trend by Jonckheere-Terpstra test p < 0.05. 446 Company Sanitized. Does not contain TSCA CBI H-24516: Subchronic Toxicity 90-Day Gavage Study in Rats with One-Generation Reproduction Evaluations DuPont-5368 TABLE 58 MEAN BODY WEIGHTS AND MEAN BODY WEIGHT GAINS OF Fi FEMALE RATS GROUP DOSE (mg/kg/day) N DAYS ON TEST3 1 8 15 22 29 36 II- 1 0 13 57. 3(6.3)^> 94. 0(7.8) 135. 8(9.6) 167. 5(13.4) 190. 0(17.5) 206. 4(16.3) IV-1 25 17 VI-1 100 12 MEAN BODY WEIGHT (grams) 58.6(6.3) 94.8(8.3) 139.6(13.9) 173.7(21.6) 195.6(24.2) 218.8(30.7) c 56 .7(4.9) 90 .4(7.0) 133 .6(8.3) 167 .5(10.8) 191 .4(15.8) 212 .6((17.7) VIII- 1 250 12 44.7 (8. 1)* 80.0(9. 6)* 124.8(9. 1)* 161.7(9. 8) 187.7 (13 .4) 206.3(13 .9) GR OUP DC3SE (mg/k g/day) N I:r-i 0 13 IV-1 25 17 VI-1 100 12 DAY S ON TE ST3 MEAN BODY WEIGE[T GA:IN (g rams) 1 -8 8-15 15-22 22-29 29-36 36 .8 (4. 2)t> 41 .8 (6. 4) 31 .7 (8. 4) 22 .5 (6. 1) 16 .4 (7. 0) 36 .2(3. 8) 44 .7(7. 1) 34 .2(9. 1) 21 .9(7. 7) 22 .6(9. l}c 33 .7(5. 4) 43 .2(5. 7) 33 .9(5. 4) 23 .9(6. 9) 21 .1(4. 2) 1 -36 149 .1 (17 .7) 160 .3 (26 .7)0 155 .9(16 .3) a Day of Weaning = Test Day 1. b Standard deviation is reported in parentheses. c N = 16. 1^111-1 250 12 35 .2(6.4) 44 .8(4.1) 36 .9(5.6) 26 .0(8.3) 18 .6(13.1) 161 .5(18.7) Statistically significant trend by Jonckheere-Terpstra test; p < 0.05, 447 Conmany S<n'ed. noes "oil cinta'i TSCA CBI H-24516: Subchronic Toxicity 90-Day Gavage Study in Rats with One-Generation Reproduction Evaluations DuPont-5368 TABLE 59 SUMMARY OF CLINICAL OBSERVATIONS IN Fi RATS Pi MALE RATS DOSE GROUP (mg/kg/day) N Number of Rats with Given Observation 1-1 0 III-l 25 V-l 100 VII-1 250 13 16 12 12 OBSERVATIONS There were no abnormal Total No. of Rats with Fi FEMALE RATS clinical Masses observations observed in the Pi Male Rats. 0000 Number of Rats with Given Observation DOSE GROUP (mg/kg/day) N II-l 0 13 IV-1 25 17 VI-1 100 12 VIII- 1 250 12 OBSERVATIONS Alopecia 0 1 0 0 Total No. of Rats with Masses 0 0 0 0 There were no statistically significant trends by Cochran-Armitage test; p < 0.05. 448 Company Sanitized. Does not contain TSCA CBI H-24516: Subchronic Toxicity 90-Day Gavage Study in Rats with One-Generation Reproduction Evaluations____________DuPont-5368 TABLE 60 SUMMARY OF DEVELOPMENTAL LANDMARKS IN Fi RATS PREPUTIAL SEPARATION - Fi MALE RATS III-l GROUP 1-1 V-l DOSE (mg/kg/day) 0 25 100 N 13 16 12 VII-1 250 12 AGE (Days)a 39.9 ______________________(2.22) 41.5 (2.90) 43.2 (3.16) 42.7 (2.10) VAGINAL OPENING - Fi FEMALE RATS DOSE GROUP (mg/kg/day) N II-l 0 13 IV-1 25 17 VI-1 100 12 VIII-1 250 12 AGE (Days)a 32.1 (2.43) 32.2 (2.28) 32.1 (1.93) 32.5 (2.58) Data summarized as: Mean Standard Deviation a Age was calculated as follows using data presented in Appendix LL: Test day + 20 days = Age (days). There were no statistically significant trends by linear contrast of least square means (covariate:body weight). 449 Company Sanitized. Does not contain TSCA CBI Cfl pC--IHMiiW nAA*----wJ*t_VfMB nnf H-24516: Subchronic Toxicity 90-Day Gavage Study in Rats with One-Generation Reproduction Evaluations TABLE 61 MEAN FINAL BODY AND ORGAN WEIGHTS FROM MALE RATS - Pi ADULTS GROUP 1-0 DOSE (MG/KG/DAY) 0 III-O V-0 25 100 VII-0 250 THYROID 0.021 0.003(12 ) 0.020 0.004(17 ) FINAL BODY 604.692 62.781(12 ) 594.429 57.077(17 ) THYROID/FINAL BODY * 100 0.004 0.000(12 ) 0.003 0.001(17 ) Data summarized as: Mean Standard Deviation (n) Statistical Methods: Trend test (Jonckheere-Terpstra). # Statistically significant difference at p < 0.05. 0.022 0.005(14 ) 557.193 61.905(14 ) 0.004 0.001(14 ) 0.025 0.007(14 ) 541.471ft 65.972(14 ) 0.005# 0.001(14 ) 450 Company Sanitized. Does not eon H-24516: Subchronic Toxicity 90-Day Gavage Study in Rats with One-Generation Reproduction Evaluations TABLE 62 MEAN FINAL BODY AND ORGAN WEIGHTS FROM FEMALE RATS - Pi ADULTS GROUP DOSE (MG/KG/DAY) II -0 0 IV-0 25 THYROID 0. 019 0. 004(11 ) 0.021 0.004(17 ) FINAL BODY 351. 700 33 . 050(11 ) 365.888 18.416(17 ) THYROID/FINAL BODY * 100 0. 006 0. 001(11 ) 0.006 0.001(17 ) Data summarized as: Mean Standard Deviation (n) Statistical Methods: Trend test (Jonckheere-Terpstra) No statistically significant difference at p < 0.05. VI -0 100 0. 020 0. 004(12 ) 359. 208 15. 076(12 ) 0. 006 0. 001(12 ) VIII- 0 250 0.022 0.005 (12 ) 338.008 41.391 (12 ) 0.006 0 .002 (12 ) 451 Company Sanitized. Does not contain H-24516: Subchronic Toxicity 90-Day Gavage Study in Rats with One-Generation Reproduction Evaluations TABL,E63 MEAN FIN AL BODY ANDC>RGANW EIGHTSi FR01VIM[ALER.'VTS- Fi ADU]LTS MEAN FINAL BODY AND ABSOLUTE ORGAN WE:[GHTS ( grams3) GROUP DOSE (MG/KG/DAY) 1-1 in-:L 0 25 V -1 1 00 i/ll-i 250 BRAIN EPIDIDYMIDES TESTES SEMINAL VESICLES PROSTATE THYROID KIDNEYS LIVER FINAL BODY 1.996 0.093 (13 ) 0.760 0.067 (13 ) 3 .300 0.228(13 ) 1.200 0.205 (13 ) 0.460 0.126 (13 ) 0.019 0.004 (13 ) 3 .283 0.291 (13 ) 17.488 1.869 (13 ) 384.823 31.437 (13 ) 1 .949 0 .069 (16 ) 0 .738 0 .092 (16 ) 3 .154 0 .177 (16 ) 1 .074 0 .202 (16 ) 0 .409 0 .083 (16 ) 0 .017 0 .003 (16 ) 3 .154 0 .264 (16 ) 16 .938 1 .829 (16 ) 372 .338 25 .695 (16 ) 1. 966 0. 106 (12 ) 0. 739 0. 048 (12 ) 3 . 220 0. 254 (12 ) 1. 085 0. 257 (12 ) 0 . 368 0. 087 (12 ) 0. 015 0. 004 (12 ) 3 . 199 0. 293 (12 ) 17. 100 2. 729 (12 ) 376.133 26.968 (12 ) i .978 0 .072(12 ) 0 .686# 0 .065(12 ) 3 039ft 0 .439(12 ) 1 .084 0 .187(12 ) 0 .406 0 .116(12 ) 0 .018 0 .004(12 ) 3 .253 0 .270(12 ) 16 .037# 1 .240(12 ) 360 375# 36 .754(12 ) 452 Company Sanitized. Does not con H-24516: Subchronic Toxicity 90-Day Gavage Study in Rats with One-Generation Reproduction Evaluations TABLE 63 (Continued) MEAN FINAL BODY AND ORGAN WEIGHTS FROM MALE RATS - Fi ADULTS MEAN RELATIVE ORGAN WEIGHTS (% of body weight) GROUP DOSE (MG/KG/DAY) 1-1 0 III-l 25 V-l 100 VII-1 250 BRAIN/FINAL BODY * 100 0.521 0.034(13 ) EPIDIDYMIDES/PINAL BODY * 100 0.198 0.014(13 ) TESTES/FINAL BODY * 100 0.860 0.044(13 ) SEMINAL VESICLES/FINAL BODY * 100 0.311 0.037(13 ) PROSTATE/FINAL BODY * 100 0.119 0.029(13 ) THYROID/FINAL BODY * 100 0.005 0.001(13 ) KIDNEYS/FINAL BODY * 100 0.854 0.051(13 ) 0.525 0.028(16 ) 0.198 0.019(16 ) 0.848 0.034(16 ) 0.288 0.045(16 ) 0.110 0.020(16 ) 0.005 0.001(16 ) 0.848 0.061(16 ) 0.525 0.049(12 ) 0.197 0.014(12 ) 0.860 0.091(12 ) 0.287 0.055(12 ) 0.098 0.022(12 ) 0.004 0.001(12 ) 0.851 0.059(12 ) 0.553 0.048(12 ) 0.191 0.015(12 ) 0.843 0.077(12 ) 0.303 0.057(12 ) 0.112 0.024(12 ) 0.005 0.001(12 ) 0.906 0.068(12 ) 453 Company Sanitized. Does not co h m^ H-24516: Subchronic Toxicity 90-Day Gavage Study in Rats with One-Generation Reproduction Evaluations TABLE 63 (Continued) MEAN FINAL BODY AND ORGAN WEIGHTS FROM MALE RATS - Fi ADULTS MEAM RELATIVE ORGAN WEIGHTS (% of body weight) GROUP DOSE (MG/KG/DAY) 1-1 0 III-l 25 V-l 100 VII-1 250 LIVER/FINAL BODY * 100 4.543 0.290(13 ) 4.546 0.327(16 ) 4.525 0.479(12 ) 4.468 0.329(12 ) MEAN RELATIVE ORGAN WEIGHTS (organ to brain wei9ht ratio) GROUP DOSE (MG/KG/DAY) 1-1 0 I25II-l LIVER/BRAIN*100 KIDMEYS/BRAIN*100 875.891 82.315(13 ) 164.486 12.752(13 ) 868.962 90.420(16 ) 161.723 11.469(16 ) PROSTATE/BRAIM*100 23.017 5.990(13 ) 20.936 4.034(16 ) SEMINAL VESICLES/BRAIN*100 59.952 8.655(13 ) 55.060 10.071(16 ) TESTES/BRAIN*100 165.435 9.973(13 ) 161.842 8.064(16 ) V-l 100 873.051 149.566(12 ) 163.152 17.372(12 ) 18.712 4.085(12 ) 55.069 12.064(12 ) 164.109 14.137(12 ) VII-1 250 811.923 70.037(12 ) 164.691 14.841(12 ) 20.513 5.677(12 ) 54.769 9.181(12 ) 153.809 22.378(12 ) 454 Company Sanitized. Does no H-24516: Subchronic Toxicity 90-Day Gavage Study in Rats with One-Generation Reproduction Evaluations TABLE 63 (Continued) MEAN FINAL BODY AND ORGAN WEIGHTS FROM MALE RATS - Fi ADULTS EPIDIDYMIDES/BRAIN*100 38.113 3.175(13 ) 37.831 4.196(16 ) THYROID/BRAIN*100 0.953 0.215(13 ) 0.861 0.163(16 ) Data summarized as: Mean Standard Deviation (n) Statistical Methods: Trend test (Jonckheere-Terpstra). ft Statistically significant difference at p < 0.05. 37.650 2.899(12 ) 0.775 0.192(12 ) 34.712# 3.437(12 ) 0.933 0.221(12 ) 455 Company Sanitized. Does not c H-24516: Subchronic Toxicity 90-Day Gavage Study in Rats with One-Generation Reproduction Evaluations TABLE 64 MEAN FINAL BODY AND ORGAN WEIGHTS FROM FEMALE RATS - Fi ADULTS MEAN FINAL BODY AND ABSOLUTE ORGAN WEIGHTS (grams) GROUP DOSE (MG/KG/DAY) 11-1 0 IV-1 25 VI-1 100 VIII -1 250 BRAIN UTERUS THYROID KIDNEYS LIVER FINAL BODY 1 .829 0 .061 (13 ) 0 .429 0 .087 (13 ) 0 .016 0 .003 (13 ) 1 .886 0 .154 (13 ) 9 .063 1 .385 (13 ) 218 .431 19 .969 (13 ) 1 .849 0 .082 (17 ) 0 .470 0 . 140 (17 ) 0 .015 0 .003 (17 ) 2 .038 0 .249 (17 ) 9 .589 1 .727 (17 ) 226 .071 29 .359 (17 ) 1 .799 0 .091 (12 ) 0 .450 0 .115 (12 ) 0 .016 0 .003 (12 ) 2 .051 0 .247 (12 ) 9 .593 1 .329 (12 ) 223 .750 19 .600 (12 ) 1 .810 0 .057 (12 ) 0 .583 0 .604 (12 ) 0 .013 0 .002 (12 ) 2 .039 0 .211 (12 ) 9 .986 0 .958 (12 ) 222 .475 15 .014 (12 ) 456 Company Sanitized. Does not c H-24516: Subchronic Toxicity 90-Day Gavage Study in Rats with One-Generation Reproduction Evaluations TABLE 64 (Continued) MEAN FINAL BODY AND ORGAN WEIGHTS FROM FEMALE RATS - Fi ADULTS MEAN RELATIVE ORGAN WEIGHTS (% of body weight) GROUP DOSE (MG/KG/DAY) I 1-1 0 IV-1 25 BRAIN/FINAL BODY * 100 0. 844 0. 083(13 ) UTERUS/FINAL BODY * 100 0. 198 0. 040(13 ) THYROID/FINAL BODY * 100 0. 007 0. 001(13 ) KIDNEYS/FINAL BODY * 100 0. 867 0 . 079(13 ) LIVER/FINAL BODY * 100 4. 136 0 . 403(13 ) 0 .829 0.096(17 ) 0.210 0.065(17 ) 0.007 0.002(17 ) 0.904 0.052(17 ) 4.227 0.406(17 ) i tf-1-l 100 0 .810 0 .085(12 ) 0 .203 0 .057(12 ) 0 .007 0 .002(12 ) 0 .921 0 .119(12 ) 4 .281 0 .361(12 ) VIII-1 250 0.817 0.061(12 ) 0.258 0.251(12 ) 0 .006 0.001(12 ) 0.917 0.079(12 ) 4.492# 0.372(12 ) MEAN RELATIVE ORGAN WEIGHTS (organ to brain weight ratio) GROUP DOSE (MG/KG/DAY) 11-1 0 IV-1 25 LIVER/BRAIN*100 496 . 052 77. 065(13 ) 517.938 86.356(17 ) VI-1 100 534 .812 80 .407(12 ) VIII-1 250 552.297ft 55.783(12 ) 457 Company Sanitized. Does not conta H-24516: Subchronic Toxicity 90-Day Gavage Study in Rats with One-Generation Reproduction Evaluations TABLE 64 (Continued) MEAN FINAL BODY AND ORGAN WEIGHTS FROM FEMALE RATS - Fi ADULTS MEAN RELATIVE ORGAN WEIGHTS (organ to brain weight ratio) GROUP DOSE (MG/KG/DAY) II-l IV-1 0 25 VI-1 100 VIII-1 250 KIDNEYS/BRAIN*100 103.192 8.825(13 ) 110.086 11.594(17 ) THYROID/BRAIN*100 0 .867 0 .164 (13 ) 0 .804 0 .187 (17 ) UTERUS/BRAIM*100 23 .473 4 .657 (13 ) 25 .407 7 .477 (17 ) Data summarized as: Mean Standard Deviation (n) Statistical Methods: Trend test (Jonckheere-Terpstra). ft Statistically significant difference at p < 0.05. 114.319ft 15.371(12 ) 0 .898 0 .189 (12 ) 24 .873 5 .632 (12 ) 112.713ft 12.284(12 ) 0 .718 0 .128 (12 ) 32 .194 33 .171 (12 ) 458 Company Sanitized. Does no H-24516: Subchronic Toxicity 90-Day Gavage Study in Rats with One-Generation Reproduction Evaluations SITE/LESION: TABLE 65 INCIDENCES OF GROSS OBSERVATIONS IN MALE RATS - Pi ADULTS GROUP DESIGNATION: 1-0 DOSE (MG/KG/DAY): 0 NUMBER IN GROUP: 20 III-O V-0 25 100 20 20 EPIDIDYMIDES LARGE Oa 0 0 a INCIDENCES REFLECT THE NUMBER OF ANIMALS WITH A GIVEN LESION. 459 Company Sanitized. Does no H-24516: Subchronic Toxicity 90-Day Gavage Study in Rats with One-Generation Reproduction Evaluations SITE/LESION: TABLE 66 INCIDENCES OF GROSS OBSERVATIONS IN FEMALE RATS - Pi ADULTS GROUP DESIGNATION: DOSE (MG/KG/DAY): NUMBER IN GROUP: II-O 0 20 IV-0 25 20 VI-0 100 20 LIVER DISCOLORATION STOMACH DISTENDED WITH GAS ia 0 0 0 0 0 SMALL INTESTINE DISTENDED WITH GAS 0 0 0 KIDNEYS DILATATION 0 0 0 UTERUS HEMORRHAGE OBSTRUCTION 0 0 0 0 0 0 SKIN STAIN ALOPECIA 0 0 1 1 0 0 a INCIDENCES REFLECT THE NUMBER OF ANIMALS WITH A GIVEN LESION. 460 Company Sanitized. Does not co H-24516: Subchronic Toxicity 90-Day Gavage Study in Rats with One-Generation Reproduction Evaluations SITE/LESION: TABLE 67 INCIDENCES OF GROSS OBSERVATIONS IN MALE RATS - Fi PUPS DAM GROUP DESIGNATION: DOSE (MG/KG/DAY): NUMBER PUPS/LITTERS: II-O 0 1/1 IV-0 25 2/2 VI-0 100 7/3 STOMACH NO MILK SPOT PERITONEAL CAVITY CANNIBALIZED LUNGS NOT EXPANDED 0(0) 2(2) 4(1) 0(0) 0(0) 0(0) 0(0) 2(2) 4(1) TOTAL LITTERS AFFECTED TOTAL PUPS AFFECTED For each group: The count of pups only includes those which underwent pathological examin The count of litters only includes those in which pups underwent patholog For each site/lesion: Numbers outside the parentheses are the number of pups affected. Numbers in parentheses are the number of litters affected. 461 Company Sanitized. Does not c H-24516: Subchronic Toxicity 90-Day Gavage Study in Rats with One-Generation Reproduction Evaluations SITE/LESION: TABLE 68 INCIDENCES OF GROSS OBSERVATIONS IN FEMALE RATS - Fi PUPS DAM GROUP DESIGNATION: DOSE (MG/KG/DAY): NUMBER PUPS/LITTERS: II-O 0 0/0 IV-0 25 0/0 VI-0 100 8/3 STOMACH NO MILK SPOT 0(0) 0(0) 5(1) LUNGS NOT EXPANDED 0(0) 0(0) 5(1) TOTAL LITTERS AFFECTED TOTAL PUPS AFFECTED For each 9roup: The count of pups only includes those which underwent pathological examin The count of litters only includes those in which pups underwent patholog 0 0 15 1 For each site/lesion: Numbers outside the parentheses are the number of pups affected. Numbers in parentheses are the number of litters affected. 462 CBInpanysanm2ed- ^"ot H-24 516: Subchronic Toxicity 90-Day Gavage Study in Rats with One-Generation Reproduction Evaluations SITE/LESION: TABLE 69 INCIDENCES OF GROSS OBSERVATIONS IN RATS - Fi UNSEXABLE PUPS DAM GROUP DESIGNATION: DOSE (MG/KG/DAY): NUMBER PUPS/LITTERS: II-O 0 0/0 IV-0 25 0/0 VI-0 100 0/0 WHOLE BODY AUTOLYSIS 0(0) 0(0) 0(0) TOTAL LITTERS AFFECTED TOTAL PUPS AFFECTED 0 0 0 For each group: The count of pups only includes those which underwent pathological examin The count of litters only includes those in which pups underwent patholog 0 0 0 1 For each site/lesion: Numbers outside the parentheses are the number of pups affected. Numbers in parentheses are the number of litters affected. 463 Comoany SwHIzed. Does no H-24516: Subchronic Toxicity 90-Day Gavage Study in Rats with One-Generation Reproduction Evaluations SITE/LESION: TABLE 70 INCIDENCES OF GROSS OBSERVATIONS IN MALE RATS - Fi WEANLINGS GROUP DESIGNATION: 1-1 DOSE (MG/KG/DAY): 0 NUMBER IN GROUP: 42 2I5II-l V-l 100 45 34 KIDNEYS LARGE SMALL 0s 1 0 0 1 0 a INCIDENCES REFLECT THE NUMBER OP ANIMALS WITH A GIVEN LESION. 464 ^^.D^ H-24516: Subchronic Toxicity 90-Day Gavage Study in Rats with One-Generation Reproduction Evaluations SITE/LESION: TABLE 71 INCIDENCES OF GROSS OBSERVATIONS IN FEMALE RATS - Fi WEANLINGS GROUP DESIGNATION: DOSE (MG/KG/DAY): NUMBER IN GROUP: II-l 0 36 IV-1 25 51 VI-1 100 30 THERE WERE NO GROSS OBSERVATIONS 465 Company Sanitized. Does no! con w . ^ H-24516: Subchronic Toxicity 90-Day Gavage Study in Rats with One-Generation Reproduction Evaluations SITE/LESION: TABLE 72 INCIDENCES OF GROSS OBSERVATIONS IN MALE RATS - Fi ADULTS GROUP DESIGNATION: 1-1 DOSE (MG/KG/DAY): 0 NUMBER IN GROUP: 13 III-l V-l 25 100 16 12 KIDNEYS DILATATION _________________^-a__________3__________6_______ a INCIDENCES REFLECT THE NUMBER OF ANIMALS WITH A GIVEN LESION. 466 Company Sanitized. Does not c H-24516: Subchromc Toxicity 90-Day Gavage Study in Rats with One-Generation Reproduction Evaluations SITE/LESION: TABLE 73 INCIDENCES OF GROSS OBSERVATIONS IN FEMALE RATS - Fi ADULTS GROUP DESIGNATION: DOSE (MG/KG/DAY): NUMBER IN GROUP: II-l 0 13 IV-1 25 17 VI-1 100 12 0 0 2 0 KIDNEYS DILATATION a INCIDENCES REFLECT THE NUMBER OF ANIMALS WITH A GIVEN LESION. 467 Company Sanitized. Does not c H-24516: Subchronic Toxicity 90-Day Gavage Study in Rats with One-Generation Reproduction Evaluations TABLE 74 INCIDENCES AND LESION GRADES OF MICROSCOPIC OBSERVATIONS IN MALE REPRODUCTION RATS - Pi ADULTS GROUP DESIGNATION: 1-0 LESION GRADES DOSE (MG/KG/DAY): 0 TISSUE/LESION (P,l, 2,3,4) NUMBER IN GROUP: 20 '= III-0 V-0 25 100 20 20 TESTIS'3 TESTES 4 ! 3^ J3 2 3 EPIDIDYMIS'2 EPIDIDYMIDES PROSTATE INFLAMMATION, SUBACUTE/CHRONIC SEMINAL VESICLES COAGULATING GLAND OTHER 4 ] 3^ 2 7 3 1 (-, 1,-,-,-) 7 3^ 1 3 0 0 3^ 3 6 1 (-,1, -,-, ^ 6 0 0 THE NUMBER OF ORGANS EXAMINED FOR EACH GROUP IS UNDERLINED. 0 LESION GRADES: P = PRESENT; 1 = MINIMAL; 2 = MILD; 3 = MODERATE; 4 = SEVERE. o LESION GRADES CORRESPOND BY POSITION WITH THE NUMBERS IN PARENTHESES, WHICH INDICATE HOW OFTEN (-,1,2,-,-) WAS OBSERVED. FOR EXAMPLE: MEANS NO LESIONS WERE GRADED "PRESENT" (NON-GRADED LE 1 LESION WAS GRADED "MINIMAL", 2 LESIONS WERE GRADED "MILD", NO LESIONS WERE GRADED "MODERATE" WERE GRADED "SEVERE". a One of the pair available for microscopic examination. Sperm parameter evaluation was p second of the pair. 468 Company Sanitized. Does not H-24516: Subchronic Toxicity 90-Day Gavage Study in Rats with One-Generation Reproduction Evaluations TABLE 75 INCIDENCES AND LESION GRADES OF MICROSCOPIC OBSERVATIONS IN FEMALE REPRODUCTION RATS - P, ADULTS TISSUE/LESION LESION GRADES (P,1,2,3,4) GROUP DESIGNATION: DOSE (MG/KG/DAY): NUMBER IN GROUP: II-O 0 20 IV-0 25 20 VI-0 100 20 OVARIES UTERUS DILATATION, GLAND/LUMEN VAGINA 1 (-,!,-, 3 3 (-,1,2,- 8 OTHER LIVER: NECROSIS, FOCAL SKIN: NO ABNORMALITIES DETECTED (-,!,-,-,-) (1,-,-,-,-) THE NUMBER OF ORGANS EXAMINED FOR EACH GROUP IS UNDERLINED. LESION GRADES: P = PRESENT; 1 = MINIMAL; 2 = MILD; 3 = MODERATE; 4 = SEVERE. LESION GRADES CORRESPOND BY POSITION WITH THE NUMBERS IN PARENTHESES, WHICH INDICATE HOW OFTE (-,1,2,-,-) WAS OBSERVED. FOR EXAMPLE: MEANS NO LESIONS WERE GRADED "PRESENT" (NON-GRADED L 1 LESION WAS GRADED "MINIMAL", 2 LESIONS WERE GRADED "MILD", NO LESIONS WERE GRADED "MODERATE WERE GRADED "SEVERE". 469 6omoany Sanitized. Does not H-24516: Subchronic Toxicity 90-Day Gavage Study in Rats with One-Generation Reproduction Evaluations DuPont-5368 FIGURES 470 Company Sanitized. Does not contain TSCA CBf H-24516: Subchronic Toxicity 90-Day Gavage Study in Rats with One-Generation Reproduction Evaluations DuPont-5368 FIGURES EXPLANATORY NOTES Critical Dates Day 74 Male and female rats designated for reproduction evaluations were co-housed. Body weights collected during the cohabitation and post-mating periods are reported in the Reproductive Toxicology section. Day 90 Recovery period begins for rats designated for one-month and 3-month recovery periods. Day 91 Male rats designated for the 90-day exposure period were sacrificed. Day 92 Last day of test substance administration for female rats designated for the 90-day exposure period. Day 93 Female rats designated for 90-day exposure period were sacrificed. Day 119 Last day of non-fasted body weight data collection for rats designated for the one-month recovery period. Day 125 Male and female rats designated for the one-month recovery period were sacrificed Day 175 Last day of non-fasted body weight data collection for rats designated for the 3-month recovery period. Day 181 Male and female rats designated for 3-month recovery period were sacrificed. 471 ^mpMy sm6^ ^ M ow TOO ^p ^ ^Ste H-24516: Subchronic Toxicity 90-Day Gavage Study in Rats with One-Generation Reproduction Evaluations FIGURE 1 MEAN BODY WEIGHTS OF MALE RATS * On test day 74, male and female rats designated for reproduction evaluations were co-housed. On test day 77, all rats in the 250 nig/kg/day dose group were placed on ground chow. 472 H-24516: Subchronic Toxicity 90-Day Gavage Study in Rats with One-Generation Reproduction Evaluations FIGURE 2 MEAN BODY WEIGHTS OF FEMALE RATS * On test day 74, male and female rats designated for reproduction evaluations were co-housed. On test day 77, all rats in the 250 nig/kg/day dose group were placed on ground chow. 473 Oow not con H-24516: Subchronic Toxicity 90-Day Gavage Study in Rats with One-Generation Reproduction Evaluations FIGURE 3 MEAN FORELIMB GRIP STRENGTH FOR MALE RATS D 0m il25m ^lOO 250 Baseline Week 13 Assessment Period 474 Recovery Company Sanitized. Does not c w H-24516: Subchronic Toxicity 90-Day Gavage Study in Rats with One-Generation Reproduction Evaluations FIGURE 4 MEAN FORELIMB GRIP STRENGTH FOR FEMALE RATS D 0 mg/kg/d B125 mg/kg/ ^lOOmgkgd 1250 mg/kg Baseline Week 13 Assessment Period 475 Recovery companysanwled- ^"otconte H-24516: Subchronic Toxicity 90-Day Gavage Study in Rats with One-Generation Reproduction Evaluations FIGURE 5 MEAN HINDLIMB GRIP STRENGTH FOR MALE RATS 1.20 -1 1.00 4 ^ 0.80 -I ^ 0.60 -) &. f|i 0.40 -I .B5 0.20 -\ 0.00 Baseline Week 13 Assessment Period Recovery 476 colnanyj D 0 II125 ^lO 25 (con H-24516: Subchronic Toxicity 90-Day Gavage Study in Rats with One-Generation Reproduction Evaluations FIGURE 6 MEAN HINDLIMB GRIP STRENGTH FOR FEMALE RATS 0.90 -1 D 0 mg H 25 mg H100 m 1250 m Baseline Week 13 Assessment Period 477 Recovery Company Sanitized. Does not c w H-24516: Subchronic Toxicity 90-Day Gavage Study in Rats with One-Generation Reproduction Evaluations FIGURE 7 MOTOR ACTIVITY ASSESSMENT; MEAN DURATION OF MOVEMENTS FOR MALE RA D 0m El 25 EilOO 250 Baseline Week 13 Assessment Period Recovery 478 vaMm's^-'^^^ H-24516: Subchronic Toxicity 90-Day Gavage Study in Rats with One-Generation Reproduction Evaluations FIGURE 8 MOTOR ACTIVITY ASSESSMENT: MEAN DURATION OF MOVEMENTS FOR FEMALE R DOmg/kg/d 9 25 mg/kg ^lOOmgkg 250 mg/k Baseline Week 13 Assessment Period 479 Recovery I contai H-24516: Subchronic Toxicity 90-Day Gavage Study in Rats with One-Generation Reproduction Evaluations FIGURE 9 MOTOR ACTIVITY ASSESSMENT: MEAN NUMBER OF MOVEMENTS FOR MALE RA D 0 mg/kg/ 1125 mg/kg 100 mgk 250 mg/k Baseline Week 13 Assessment Period 480 Recovery Company Sanitized. Does H-24516: Subchronic Toxicity 90-Day Gavage Study in Rats with One-Generation Reproduction Evaluations FIGURE 10 MOTOR ACTIVITY ASSESSMENT: MEAN NUMBER OF MOVEMENTS FOR FEMALE R D 0m il25m ^100 25 Baseline Week 13 Assessment Period 481 Recovery Company Sanitized. Does not con H-24516: Subchronic Toxicity 90-Day Gavage Study in Rats with One-Generation Reproduction Evaluations DuPont-5386 APPENDICES 482 Company SanKlzed. Does not contain TSCA CBI H-24516: Subchronic Toxicity 90-Day Gavage Study in Rats with One-Generation Reproduction Evaluations______________DuPont-5386 APPENDIX A ANALYTICAL DATA 483 Company SanHIzed. Does not corttotn TSCA C8I H-24516: Subchronic Toxicity 90-Day Gavage Study in Rats with One-Generation Reproduction Evaluations DuPont-5386 Table I. Initial Homogeneity and Stability of H-24516 in Dosing Suspensions Sample ' mg/mL H-24516 Type Test Day 0 Nominal Measured Homoeeneitv CONTROL 0.00 ND(^ TOP MIDDLE BOTTOM 2.5 2.30 2.5 2.47 2.5 2.40 MeanW: 2.390.08 C.V.3% TOP MIDDLE BOTTOM(C) 10 8.97 10 10.2 10 1^ II-W MeanW: C.V.24% Percent Nominal 92.0 98.8 96.0 (95.6%) 89.7 102.0 140.0 (^^ TOP MIDDLE BOTTOM Stability^ 25 26.8 25 24.8 25 23.5 MeanW: 25.0L6 C.V. 7% 2.5 2.06 10 8.89 25 24.1 107.2 99.2 94.0 (190.0%) 82.4 88.9 96.4 Test Day 6 Homoeeneitv CONTROL 0.00 ND(A) TOP MIDDLE BOTTOM 10 9.26 10 9.58 10 9.23 MeanW: 9.36O.I9 C.V. 2% 92.6 95.8 92.3 (93.6%) Stability^ 10 9.03 90.3 (A) Denotes not detected. (B) The average measured concentration, average percent of nominal (in parentheses), standard deviation, and coefficient of variation of top, middle, and bottom are based on measured concentration for each level. (C) Duplicate re-analysis of original sample supports the original analysis and will not be reported. (D) Stability samples held 5 hours a room temperature. 484 Company Sanded. Does not contain TSCA CBI H-24516: Subchronic Toxicity 90-Day Gavage Study in Rats with One-Generation Reproduction Evaluations DuPont-5386 Table II. Mixing and Stability Study of H-24516 in Dosing Suspensions Sample Type mg/mL H-24516 Dose Volume Nominal Measured Homoeeneitv 7.5 mL/Ke CONTROL 0.00 Nn(A) Percent Nominal TOP MIDDLE BOTTOM 5.0mL/Kg CONTROL 3.33 2.88 3.33 2.54 3.33 2.67 MeanW: 2.700.2 C.V.6% 0.00 ND(^ 86.5 76.3 80.2 (81.1%) TOP MIDDLE BOTTOM TOP MIDDLE BOTTOM TOP MIDDLE BOTTOM 5.0 4.53 5.0 4.25 5.0 4.39 MeanW:^99.14 C.V.3% 20.0 19.9 20.0 17.7 20.0 18.6 ^-W MeanW: C.V.6% 50.0 53.4 50.0 52.6 50.0 54.0 MeanW: 53.4f0.7 C.V.l% 90.6 85.0 87.8 (87.8%) 99.5 88.5 93.0 f93-50^ 106.8 105.2 108.0 (106.8%) Stability 7.5 mL/Kg O-DAY ROOM TEMPERATURE 3.33 2.70 81.1 5-HoUR ROOM TEMPERATURE 3.33 2.66 79.9 4-DAY REFRIGERATED 3.33 2.94 88.3 3.33 2.88 86.5 MeanW.9I0.04 (87.4%) C.V.l% 4-DAY REFRIGERATED/5 HOUR RT 3.33 2.74 82.3 (A) Denotes not detected. (B) The average measured concentration, average percent of nominal (in parentheses), standard deviation, and coefficient of variation of top, middle, and bottom are based on measured concentration for each level. (C) The average measured concentration, average percent of nominal (in parentheses), standard deviation, and coefficient of variation of duplicate samples are based on measured concentration for each level. 485 CoihpanySanHbed. Does not contain TSCACBI H-24516: Subchronic Toxicity 90-Day Gavage Study in Rats with One-Generation Reproduction Evaluations DuPont-5386 Table II. Mixing and Stability Study of H-24516 in Dosing Suspensions (continued) Sample Type mg/mL H-24516 Dose Volume Stability Nominal Measured 5.0mL/Kg O-DAY ROOM TEMPERATURE 5.0 4.39 5-HOUR ROOM TEMPERATURE 5.0 4.60 2-DAY REFRIGERATED 5.0 4.77 5.0 4.76 3-DAY REFRIGERATED 4-DAY REFRIGERATED 4-DAY REFRIGERATED/5 HOUR RT MeanW.77.0.01 C.V. 0.2% 5.0 4.74 5.0 4.48 Mean(C): 4.610.2 C.V. 4% 5.0 4.81 5.0 4.85 Percent Nominal 87.8 92.0 95.4 95.2 (95.4%) 94.8 89.6 (92.2%) 96.1 97.1 0-DAY ROOM TEMPERATURE 5-HOUR ROOM TEMPERATURE 2-DAY REFRIGERATED 3-DAY REFRIGERATED 4-DAY REFRIGERATED 4-DAY REFRIGERATED/5 HOUR RT 20.0 20.0 20.0 20.0 20.0 20.0 20.0 20.0 18.7 17.2 18.7 18.0 Mean(C): 1S.310.5 C.V. 3% 39.3 19A MeanW: 29.414 C.V. 47% 19.6 17.6 93.5 86.0 93.5 90.0 (91.5%) 196.4 97.8 (147.0%) 97.8 88.2 0-DAY ROOM TEMPERATURE 50.0 53.4 106.8 5-HOUR ROOM TEMPERATURE 50.0 48.3 96.6 2-DAY REFRIGERATED 3-DAY REFRIGERATED 50.0 50.0 50.0 50.0 47.3 48.4 Mean(C): 47.90.8 C.V. 2% 46.5 46.9 Mean(C): 46.70.3 94.7 96.8 (95.8%) 93.0 93.8 (93.4%) 4-DAY REFRIGERATED 50.0 C.V.1% 48.9 97.8 4-DAY REFRIGERATED/5 HOUR RT 50.0 47.9 95.7 (A) Denotes not detected. (B) The average measured concentration, average percent of nominal (in parentheses), standard deviation, and coefficient of variation of top, middle, and bottom are based on measured concentration for each level. (C) The average measured concentration, average percent of nominal (in parentheses), standard deviation, and coefficient of variation of duplicate samples are based on measured concentration for each level. (D) Result is the mean of the duplicate re-analysis of the original sample. Original analysis indicated aliquot error and will not be reported. 486 CompanySanKKed. Doe, not ^nf,,n rsCA C9f H-24516: Subchronic Toxicity 90-Day Gavage Study in Rats with One-Generation Reproduction Evaluations DuPont-5386 Table III. Final Homogeneity/Concentration Verification of H-24516 in Dosing Suspensions Sample mg/mL H-24516 Percent Type Nominal Measured Nominal Test Day 49 Homoeeneitv CONTROL 0.00 ND(^ ---- TOP MIDDLE BOTTOM TOP MIDDLE BOTTOM TOP MIDDLE ' BOTTOM 3.33 3.33 3.33 13.33 13.33 13.33 33.33 33.33 33.33 MeanW: MeanW: MeanW: 2.71 2.99 3A2 3.04f0.4 C.V.12% 10.8 12.7 12^ 1W.1 C.V.9% 31.0 32.4 33A 32.3L2 C.V.4% 81.4 89.8 102.8 (91.3%) 81.0 95.3 96.3 (90.8%) 92.9 97.1 100.3 (96.8%) Test Day 91 CONTROL Homoeeneitv TOP MIDDLE BOTTOM 0.00 ND(A) 3.33 3.05 3.33 3.00 3.33 3.01 MeanW: 3.020.03 C.V.1% 91.6 90.1 90.4 (90.7%) Concentration Verification 13.33 13.33 Mean^): 12.8 12.2 12.5f0.4 C.V.3% 96.0 91.5 (93.8%) 33.33 32.7 98.1 33.33 323 96.6 Mean^: 32.51.0.3 C.V.1% (97.5%) (A) Denotes not detected. (B) The average measured concentration, average percent of nominal (in parentheses), standard deviation, and coefficient of variation of top, middle, and bottom are based on measured concentration for each level. (C) The average measured concentration, average percent of nominal (in parentheses), standard deviation, and coefficient of variation of duplicate samples are based on measured concentration for each level. ^^ompany 8an.tized.Does not contain TSCACBI H-24516: Subchronic Toxicity 90-Day Gavage Study in Rats with One-Generation Reproduction Evaluations Figure 1 Representative Analytical Calibration Curve DuPont-5386 0.02 0.04 0.06 O.OB 0.10 0.12 0.14 0.16 Concentration mg/mL (a) 0.02 0.04 0.06 0.08 0.10 0.12 0.14 0.16 Concentration mg/mL (b) Figure 1: 0.10 0.12 Concentration rng/mL (C) Calibration curve showing linear fit (line) to replicate peak height ratio measurements (squares) for calibration solutions of H-24516 diluted over a concentration range of 0.0302 to 0.1511 mg/mL. [(a) Retention time =3.5 minutes, (b) Retention =4.17 minutes, (c) Retention time = 4.77 minutes.] 488 CompanySanitised. Does not contain TSCA CBI H-24516: Subchronic Toxicity 90-Day Gavage Study in Rats with One-Generation Reproduction Evaluations DuPont-5386 Figure 2 Representative High Performance Liquid Chromatographv Chromatograms FID1 B, (001212SfB002F0201.D) PA Figure 2a: Representative GC chromatogram ofO mg/mL (control sample with internal H-24516isapproximately 3.5,4.1,4.7 minutes^etenHon time for mtemal standard is approximately 3.9 minutes. RD1 B. (001212SRWI8 hOB101.D) " CA 60 - 50- 40 - S 1 i ji Ins S11 30- ~ " '' , s < '; a i ". ^ . \^ i n 20 - ----- 10 - 0 3 4 6 B """ Figure 2b: Representative GC chromatogram of 2.5 mg/mL H-24516 dosing solution diluted to a nominal concentration of 0.06 mg/mL. The measured concentration of the representative solution is 2.51 mg/mL 489 Company Sanitized. Does not contain TSCA CBf H-24516: Subchronic Toxicity 90-Day Gavage Study ia Rats with One-Generation Reproduction Evaluations DuPont-5386 Figure 2 (continued) Representative High Performance Liauid ChromatoeraDhv Chromatoerams FID1 B, (001212SRWMKM401.D> ' PA 60 - 50- 40 30 20 - H a S \ n 3S) S " <D '? t: e a 10- Figure 2c: Representative GC chromatogram of 0.0756 mg/mL H-24516 analytical reference solution. 490 CompanySanlthed. Does not contain TSCA i H-24516: Subchronic Toxicity 90-Day Gavage Study in Rats with One-Generation Reproduction Evaluations______________DuPont-5386 APPENDIX B INDIVIDUAL DOSE VOLUMES (ML) 491 Company SanMzed. Does not contain TSCA CW H-24516: Subchronic Toxicity 90-Day Gavage Study in Rats with One-Generation Reproduction Evaluations INDIVIDUAL DOSE VOLUMES (ML) EXPLANATORY NOTES DuPont-5386 Critical Dates Day 74 Male and female rats designated for reproduction evaluations were cohoused. Dose volumes administered during the cohabitation and post-mating periods are documented in the study records. Day 89 Day 90 Day 92 Last day of test substance administration for male and female rats designated for one-month and 3-month recovery periods. Last day of test substance administration for male rats designated for the 90- day exposure period. Last day of test substance administration for female rats designated for the 90-day exposure period. Footnotes a. Due to error, data are missing. b. Animal may not have received total dose. c. Due to error, rat was dosed with vehicle only. d. On test day 18, all male rats and the first 11 female rats in the 25 mg/kg/day group received 37-39 mg/kg/day. Abbreviations AK Accidentally Killed FD Found Dead SE Sacrificed in extremis 492 Company Sanm^. Does not contain T8CA CW H-24516: Subchronic Toxicity 90-Day Gavage Study in Rats with One-Generation Reproduction Evaluations Day 0 Day 1 Male, I - 0 mg/kg/day 643241 2 .8 2.8 643300 2 .4 2.4 643143 2 .4 2.4 643205 2 .6 2.6 643235 2 .8 2.8 643288 2 .5 2.5 643150 2 .4 2.4 643189 2 .5 2.5 643185 2 .5 2.5 643210 2 .5 2.5 643268 2 .6 2.6 643232 2 .6 2.6 643265 2 .4 2.4 643239 2 .7 2.7 643270 2 .4 2.4 643148 2 .5 2.5 643284 2 .8 2.8 643229 2.4 2.4 643196 2 .1 2.1 643176 2 .5 2.5 643218 2 .7 2.7 643207 2 .4 -2.4 643280 2 .3 2.3 643271 2 .6 2.6 643211 2 .5 2.5 643163 2 .7 2.7 643197 2 .5 2.5 643242 2.4 2.4 643251 2 .4 2.4 643155 2 .4 2.4 643147 2 .5 2.5 643276 2 .8 2.8 643237 2 .4 2.4 643226 2 .5 2.5 643195 2.4 2.4 643246 3 .0 3.0 643253 2 .4 2.4 643262 2 .5 2.5 643172 2 .6 2.6 643303 2 .3 2.3 643304 2 .1 2.1 643162 2 .3 2.3 643254 2 .2 a 643145 2 .5 a 643204 2 .7 a Day 2 2 .8 2.4 2 .4 2 .6 2 .8 2 .5 2 .4 2 .5 2 .5 2 .5 2 .6 2 .6 2 .4 2 .7 2 .4 2 .5 2 .8 2 .4 2 .1 2 .5 2 .7 2 .4 2 .3 2 .6 2 .5 2 .7 2 .5 2 .4 2 .4 2 .4 2 .5 2 .8 2 .4 2 .5 2 .4 3 .0 2 .4 2 .5 2 .6 2 .3 2 .1 2 .3 2 .2 2 .5 2 .7 Day 3 2 .8 2 .4 2 .4 2 .6 2 .8 2 .5 2 .4 2 .5 2 .5 2 .5 2 .6 2 .6 2 .4 2 .7 2 .4 2 .5 2 .8 2 .4 2 .1 2 .5 2 .7 2.4 2 .3 2 .6 2 .5 2 .7 2 .5 2.4 2 .4 2.4 2 .5 2 .8 2 .4 2 .5 2 .4 3 .0 2.4 2 .5 2 .6 2 .3 2 .1 2 .3 2 .2 2 .5 2 .7 INDIVIDUAL DOSE VOLUMES (mL) Day 4 Day 5 Day 6 Day 7 2.8 2.4 2.4 2.6 2.8 2.5 2.4 2.5 2.5 2.5 2.6 2.6 2.4 2.7 2.4 2.5 2.8 2.4 2.1 2.5 2.7 2.4 2.3 2.6 2.5 2.7 2.5 2.4 2.4 2.4 2.5 2.8 2.4 2.5 2.4 3.0 2.4 2.5 2.6 2.3 2.1 2.3 2.2 2.5 2.7 2 .8 2.4 2 .4 2 .6 2 .8 2 .5 2 .4 2 .5 2 .5 2 .5 2 .6 2 .6 2.4 2 .7 2 .4 2 .5 2 .8 2 .4 2 .1 2 .5 2 .7 2 .4 2 .3 2 .6 2 .5 2 .7 2 .5 2 .4 2 .4 2 .4 2 .5 2 .8 2 .4 2 .5 2 .4 3 .0 2 .4 2 .5 2 .6 2 .3 2 .1 2 .3 2 .2 2 .5 2 .7 2 .8 2 .4 2 .4 2 .6 2 .8 2 .5 2 .4 2 .5 2 .5 2 .5 2 .6 2 .6 2 .4 2 .7 2 .4 2 .5 2 .8 2 .4 2 .1 2 .5 2 .7 2.4 2 .3 2 .6 2 .5 2 .7 2 .5 2.4 2.4 2 .4 2 .5 2 .8 2 .4 2 .5 2 .4 3 .0 2 .4 2 .5 2 .6 2 .3 2 .1 2 .3 2 .2 2 .5 2 .7 3 .5 3 .0 2 .9 3 .1 3 .5 3 .1 2 .9 3 .2 3 .2 3 .0 3 .2 3 .1 2 .9 3 .4 2 .9 3 .0 3 .4 2 .8 2 .6 3 .0 3 .1 2 .9 2 .8 3 .2 3 .1 3 .4 3 .2 3 .1 3 .0 2 .9 3 .1 3 .5 2 .8 2 .9 3 .0 3 .6 3 .0 3 .1 3 .2 2 .9 2 .6 2 .8 2 .7 2 .9 3 .2 Day 8 3 .5 3 .0 2 .9 3 .1 3 .5 3 .1 2 .9 3 .2 3 .2 3 .0 3 .2 3 .1 2 .9 3 .4 2 .9 3 .0 3 .4 2 .8 2 .6 3 .0 3 .1 2 .9 2 .8 3 .2 3 .1 3 .4 3 .2 3 .1 3 .0 2 .9 3 .1 3 .5 2 .8 2 .9 3 .0 3 .6 3 .0 3 .1 3.2 2 .9 2 .6 2.8 2 .7 2 .9 3 .2 Day 9 3.5 3.0 2.9 3.1 3.5 3.1 2.9 3.2 3.2 3.0 3.2 3.1 2.9 3.4 2.9 3.0 3.4 2.8 2.6 3.0 3.1 2.9 2.8 3.2 3.1 3.4 3.2 3.1 3.0 2.9 3.1 3.5 2.8 2.9 3.0 3.6 3.0 3.1 3.2 2.9 2.6 2.8 2.7 2.9 3.2 Day 1 3 3 2 3 3 3 2 3 3 3 3 3 2 3 2 3 3 2 2 3 3 2 2 3 3 3 3 3 3 2 3 3 2 2 3 3 3 3 3 2 2 2 2 2 3 493 8an1tte<>-Dees nrtco Company H-24516: Subchronic Toxicity 90-Day Gavage Study in Rats with One-Generation Reproduction Evaluations Day 12 Day 13 Male, I - 0 mg/kg/day 643241 3.5 3.5 643300 3.0 3.0 643143 2.9 2.9 643205 3.1 3.1 643235 3.5 3.5 643288 3.1 3.1 643150 2.9 2.9 643189 3.2 3.2 643185 3.2 3.2 643210 3.0 3.0 643268 3.2 3.2 643232 3.1 3.1 643265 2.9 2.9 643239 3 .4 3-4 643270 2.9 2.9 643148 3.0 3.0 643284 3.4 3.4 643229 2.8 2.8 643196 2.6 2.6 643176 3.0 3.0 643218 3.1 3.1 643207 2.9 2.9 643280 2.8 2.8 643271 3.2 3.2 643211 3.1 3.1 643163 3.4 3.4 643197 3.2 3.2 643242 3.1 3.1 643251 3.0 3.0 643155 2.9 2.9 643147 3.1 3.1 643276 3.5 3.5 643237 2.8 2.8 643226 2.9 2.9 643195 3.0 3.0 643246 3.6 3.6 643253 3.0 3.0 643262 3.1 3.1 643172 3.2 3.2 643303 2.9 2.9 643304 2.6 2.6 643162 2.8 2.8 643254 2.7 2.7 643145 2.9 2.9 643204 3.2 3.2 Day 14 4.1 3.5 3.4 3.6 4.1 3.6 3.4 3.8 3.8 3.5 3.8 3 .4 3.4 3.8 3.4 3.5 3.9 3.2 3.0 3.5 3,6 3.3 3.4 3.8 3.5 3 .9 3.6 3.6 3.5 3.5 3.6 4 .2 3.2 3.4 3.5 4.3 3.5 3.7 3.7 3.4 3.0 3.3 3.1 3.3 3.7 Day 15 4.1 3.5 3.4 3.6 4.1 3.6 3.4 3.8 3.8 3.5 3.8 3.4 3.4 3.8 3.4 3.5 3.9 3.2 3.0 3.5 3.6 3.3 3.4 3.8 3.5 3.9 3.6 3.6 3.5 3.5 3.6 4.2 3.2 3.4 3.5 4.3 3.5 3.7 3.7 3.4 3.0 3.3 3.1 3.3 3.7 INDIVI:[)UAL DOS;!i VOLUME;i (mL) Day 16 Day 17 Day 18 Day 19 4.1 4.1 4.1 4.1 3.5 3.5 3.5 3.5 3.4 3.4 3.4 3.4 3.6 3.6 3.6 3.6 4.1 4.1 4.1 4.1 3.6 3.6 3.6 3.6 3.4 3.4 3.4 3.4 3.8 3.8 3.8 3.8 3.8 3.8 3.8 3.8 3.5 3.5 3.5 3.5 3.8 3.8 3.8 3.8 3.4 3.4 3.4 3.4 3.4 3.4 3.4 3.4 3.8 3.8 3.8 3.8 3.4 3.4 3.4 3.4 3.5 3.5 3.5 3.5 3.9 3.9 3.9 3.9 3.2 3.2 3.2 3.2 3.0 3.0 3.0 3.0 3.5 3.5 3.5 3.5 3.6 3.6 3.6 3.6 3.3 3.3 3.3 3.3 3.4 3.4 3.4 3.4 3.8 3.8 3.8 3.8 3.5 3.5 3.5 3.5 3.9 3.9 3.9 3.9 3.6 3.6 3.6 3.6 3.6 3.6 3.6 3.6 3.5 3.5 3.5 3.5 3.5 3.5 3.5 3.5 3.6 3.6 3.6 3.6 4.2 4.2 4.2 4.2 3.2 3.2 3.2 3.2 3.4 3.4 3.4 3.4 3.5 3.5 3.5 3.5 4.3 4.3 4.3 4.3 3.5 3.5 3.5 3.5 3.7 3.7 3.7 3.7 3.7 3.7 3.7 3.7 3.4 3.4 3.4 3.4 3.0 3.0 3.0 3.0 3.3 3.3 3.3 3.3 3.1 3.1 3.1 3.1 3.3 3.3 3.3 3.3 3.7 3.7 3.7 3.7 Day 20 4.1 3.5 3.4 3.6 4.1 3.6 3.4 3.8 3.8 3.5 3.8 3.4 3.4 3.8 3.4 3.5 3.9 3.2 3.0 3.5 3.6 3.3 3.4 3.8 3.5 3.9 3.6 3.6 3.5 3.5 3.6 4.2 3.2 3.4 3.5 4.3 3.5 3.7 3.7 3.4 3.0 3.3 3.1 3.3 3.7 Day 21 4.5 3.9 3.8 4.1 4.6 4.1 3.6 4.3 4.2 3.9 4.3 3.8 4.0 4.3 3.8 3.8 4.3 3.5 3.3 3.9 4.0 3.6 3.8 4.3 3.9 4.4 4.2 4.0 3.9 3.9 4.0 4.7 3.6 3.7 3.8 4.7 4.0 4.2 4.3 3.9 3.4 3.7 3.3 3.7 4.1 Day 22 4.5 3.9 3.8 4.1 4.6 4.1 3.6 4.3 4.2 3.9 4.3 3.8 4.0 4.3 3.8 3.8 4.3 3.5 3.3 3.9 4.0 3.6 3.8 4.3 3.9 4.4 4.2 4.0 3.9 3.9 4.0 4.7 3.6 3.7 3.8 4. 4. 4.2 4.3 3. 3. 3. 3. 3. 4. 494 Company Sanitized. Does not con H-24516: Subchronic Toxicity 90-Day Gavage Study in Rats with One-Generation Reproduction Evaluations Day 24 Day 25 Male, I - o riKj/kg/day 643241 4.5 4.5 643300 3.9 3.9 643143 3.8 3.8 643205 4.1 4.1 643235 4.6 4.6 643288 4.1 4.1 643150 3.6 3.6 643189 4.3 4.3 643185 4.2 4.2 643210 3.9 3.9 643268 4.3 4.3 643232 3.8 3.8 643265 4.0 4.0 643239 4.3 4.3 643270 3.8 3.8 643148 3.8 3.8 643284 4.3 4 .3 643229 3 .5 3.5 643196 3.3 3.3 643176 3.9 3.9 643218 4.0 4.0 643207 3.6 -3.6 643280 3.8 3.8 643271 4.3 4.3 643211 3.9 3.9 643163 4.4 4.4 643197 4.2 4.2 643242 4.0 4.0 643251 3.9 3.9 643155 3.9 3.9 643147 4.0 4.0 643276 4 .7 4.7 643237 3.6 3.6 643226 3.7 3.7 643195 3.8 3.8 643246 4.7 4.7 643253 4.0 4.0 643262 4.2 4.2 643172 4.3 4.3 643303 3.9 3.9 643304 3.4 3.4 643162 3.7 3.7 643254 3.3 3.3 643145 3.7 3.7 643204 4,1 4.1 Day 26 4.5 3.9 3.8 4.1 4.6 4.1 3.6 4.3 4.2 3.9 4.3 3.8 4.0 4.3 3.8 3.8 4.3 3.5 3.3 3.9 4.0 3.6 3.8 4.3 3.9 4.4 4.2 4.0 3.9 3.9 4.0 4.7 3.6 3.7 3.8 4.7 4.0 4.2 4.3 3.9 3.4 3.7 3.3 3.7 4 .1 Day 27 4.5 3.9 3.8 4.1 4.6 4.1 3.6 4.3 4.2 3.9 4.3 3.8 4.0 4.3 3.8 3.8 4.3 3.5 3.3 3.9 4.0 3.6 3.8 4.3 3.9 4.4 4.2 4.0 3.9 3.9 4.0 4.7 3.6 3.7 3.8 4.7 4.0 4.2 4.3 3.9 3.4 3.7 3.3 3.7 4.1 INDIVI DUAL DOE;E! VOLUMIii (mL) Day 28 Day 29 Day 30 Day 31 5.0 5.0 5.0 5.0 4.2 4.2 4.2 4.2 4.2 4.2 4.2 4.2 4.5 4.5 4.5 4.5 5.1 5.1 5.1 5.1 4.6 4.6 4.6 4.6 3.8 3.8 3.8 3.8 4 .7 4.7 4.7 4.7 4.6 4.6 4.6 4.6 4.3 4.3 4.3 4.3 4.7 4.7 4.7 4.7 4.0 4.0 4.0 4.0 4.2 4.2 4.2 4.2 4.6 4.6 4.6 4 .6 4.1 4.1 4.1 4.1 4.1 4.1 4.1 4.1 4.7 4.7 4.7 4.7 3.7 3.7 3.7 3.7 3.5 3.5 3.5 3.5 4.3 4.3 4.3 4.3 4.3 4.3 4.3 4.3 3.9 3.9 3.9 3.9 4.1 4.1 4.1 4.1 4.7 4.7 4.7 4.7 4 .2 4.2 4.2 4.2 4.8 4.8 4.8 4.8 4.5 4.5 4.5 4.5 4.3 4.3 4.3 4.3 4.2 4.2 4.2 4.2 4.2 4.2 4.2 4.2 4.3 4.3 4.3 4.3 5.0 5.0 5.0 5.0 3.9 3.9 3.9 3.9 4.0 4.0 4.0 4.0 4.1 4.1 4.1 4.1 5.0 5.0 5.0 5.0 4.3 4.3 4.3 4.3 4.5 4.5 4.5 4.5 4.6 4.6 4.6 4.6 4.3 4.3 4.3 4.3 3.7 3.7 3.7 3.7 3.9 3.9 3.9 3.9 3.7 3.7 3.7 3.7 4.0 4.0 4.0 4.0 4.5 4.5 4.5 4.5 Day 32 5.0 4.2 4.2 4.5 5.1 4.6 3.8 4.7 4.6 4.3 4.7 4.0 4.2 4.6 4.1 4.1 4.7 3.7 3.5 4.3 4.3 3.9 4.1 4.7 4.2 4.8 4.5 4.3 4.2 4.2 4.3 5.0 3.9 4.0 4.1 5.0 4.3 4.5 4.6 4.3 3.7 3.9 3.7 4.0 4.5 Day 33 5.0 4.2 4.2 4.5 5.1 4.6 3.8 4.7 4.6 4.3 4.7 4.0 4.2 4.6 4.1 4.1 4.7 3.7 3.5 4.3 4.3 3.9 4.1 4.7 4.2 4.8 4.5 4.3 4.2 4.2 4.3 5.0 3.9 4.0 4.1 5.0 4.3 4.5 4.6 4.3 3.7 3.9 3.7 4.0 4.5 Day 34 5 4 4 4 5 4 3 4 4 4 4 4 4 4 4 4 4 3 3 4 4 3 4 4 4 4 4 4 4 4 4 5 3 4 4 5 4 4 4 4 3 3 3 4 4 495 Company SanWzed. Does not conta H-24516: Subchronic Toxicity 90-Day Gavage Study in Rats with One-Generation Reproduction Evaluations Day 36 Day 37 Male, I - 0 mg/kg/day 643241 643300 643143 643205 643235 643288 643150 643189 643185 643210 643268 643232 643265 643239 643270 643148 643284 643229 643196 643176 643218 643207 643280 643271 643211 643163 643197 643242 643251 643155 643147 643276 643237 643226 643195 643246 643253 643262 643172 643303 643304 643162 643254 643145 643204 5 .2 4 .6 4 .4 4 .7 5 .4 4 .9 4 .1 4 .9 4 .8 4.4 5 .0 4 .1 4 .4 4 .9 4 .4 4 .5 5 .0 3 .9 3 .7 4 .5 4 .6 4 .2 4 .4 5 .0 4 .5 5 .2 4 .7 4 .6 4 .4 4 .3 4 .6 5 .4 4 .1 4 .1 4 .3 5 .3 4 .6 4 .9 4 .9 4 .7 3 .9 4 .2 4 .0 4 .3 4 .7 5. 2 4. 6 4. 4 4. 7 5. 4 4. 9 4. 1 4. 9 4. 8 4. 4 5. 0 4. 1 4. 4 4. 9 4. 4 4. 5 5. 0 3 . 9 3. 7 4 .5 4. 6 -4. 2 4. 4 5. 0 4. 5 5. 2 4. 7 4. 6 4. 4 4 .3 4. 6 5. 4 4. 1 4. 1 4. 3 5. 3 4. 6 4 . 9 4.,9 4..7 3..9 4..2 4..0 4..3 4 .7 Day 38 3.9 3.4 3.3 3.5 4.0 3.7 3.1 3.7 3.6 3.3 3.8 3.1 3.3 3.7 3.3 3.3 3.8 2.9 2.B 3.4 3.4 3.2 3.3 3.7 3.3 3.9 3.5 3.5 3.3 3.2 3.5 4.1 3.0 3.1 3.2 4.0 3.4 3.7 3.7 3.5 2.9 3.1 3.0 3.3 3.5 INDIVIDUAL DOSE VOLUMES (mL) Day 39 Day 40 Day 41 Day 42 3.9 3.9 3.9 4.1 3.4 3.4 3.4 3.6 3.3 3.3 3.3 3.5 3.5 3.5 3.5 3.8 4.0 4.0 4.0 4.3 3.7 3.7 3.7 3.9 3.1 3.1 3.1 3.2 3.7 3.7 3.7 3.9 3.6 3.6 3.6 3.8 3.3 3.3 3.3 3.5 3.8 3.8 3.8 3.9 3.1 3.1 3.1 3.2 3.3 3.3 3.3 3.6 3.7 3.7 3.7 3.9 3.3 3.3 3.3 3.5 3.3 3.3 3.3 3.4 3.8 3.8 3.8 4.0 2.9 2.9 2.9 3.1 2.8 2.8 2.8 3.0 3 .4 3.4 3.4 3.6 3.4 3.4 3.4 3.6 3.2 3.2 3.2 3.3 3.3 3.3 3.3 3.5 3.7 3.7 3.7 4.0 3.3 3.3 3.3 3.5 3-9 3.9 3.9 4.1 3.5 3.5 3.5 3.7 3.5 3.5 3.5 3.7 3.3 3.3 3.3 3 .4 3.2 3.2 3.2 3.4 3.5 3.5 3.5 3.7 4.1 4.1 4.1 4.2 3.0 3.0 3.0 3.2 3.1 3.1 3.1 3.3 3.2 3.2 3.2 3.5 4.0 4.0 4.0 4 .2 3.4 3.4 3.4 3.7 3.7 3.7 3.7 3.9 3.7 3.7 3.7 3.9 3.5 3-5 3.5 3.8 2.9 2.9 2.9 3.1 3.1 3.1 3.1 3.2 3.0 3.0 3.0 3.2 3.3 3.3 3.3 3.4 3.5 3.5 3.5 3.7 Day 43 4.1 3.6 3.5 3.8 4.3 3.9 3.2 3.9 3.8 3.5 3.9 3.2 3.6 3.9 3.5 3.4 4.0 3.1 3.0 3.6 3.6 3.3 3.5 4.0 3.5 4.1 3.7 3.7 3.4 3.4 3.7 4.2 3.2 3.3 3.5 4.2 3.7 3.9 3.9 3.8 3.1 3.2 3.2 3.4 3.7 496 Company SanWzed. Does not contai H-24516: Subchronic Toxicity 90-Day Gavage Study in Rats with One-Generation Reproduction Evaluations Day 45 Male, I - 0 ing/kg/day 643241 4.1 643300 3.6 643143 3.5 643205 3.8 643235 4.3 643288 3.9 643150 3.2 643189 3.9 643185 3.8 643210 3.5 643268 3.9 643232 3.2 643265 3.6 643239 3.9 643270 3.5 643148 3.4 643284 4.0 643229 3.1 643196 3.0 643176 3.6 643218 3.6 643207 3.3 643280 3.5 643271 4.0 643211 3.5 643163 4.1 643197 3.7 643242 3.7 643251 3.4 643155 3.4 643147 3.7 643276 4.2 643237 3.2 643226 3.3 643195 3.5 643246 4.2 643253 3.7 643262 3.9 643172 3.9 643303 3.8 643304 3.1 643162 3.2 643254 3.2 643145 3.4 643204 3.7 Day 46 4.1 3.6 3.5 3.8 4.3 3.9 3.2 3.9 3.8 3.5 3.9 3.2 3.6 3.9 3.5 3.4 4.0 3.1 3.0 3.6 3.6 3.3 3.5 4.0 3.5 4.1 3.7 3 .7 3.4 3.4 3.7 4.2 3.2 3.3 3.5 4.2 3.7 3.9 3.9 3.8 3.1 3.2 3.2 3.4 3.7 Day 47 INDIV:EDUAL, DC)SE VOLUME,3 Day 48 Day 49 (mL) Day 50 4.1 4.1 4.3 4.3 3.6 3.6 3.8 3.8 3.5 3.5 3.6 3.6 3.8 3.8 3.9 3.9 4.3 4.3 4.4 4.4 3.9 3.9 3.9 3.9 3.2 3.2 3.2 3.2 3.9 3.9 3.9 3.9 3.8 3.8 3.9 3.9 3.5 3.5 3.7 3.7 3.9 3.9 4.1 4.1 3.2 3.2 3.4 3.4 3.6 3.6 3.7 3.7 3.9 3.9 4.1 4.1 3.5 3.5 3.6 3.6 3.4 3.4 3.6 3.6 4.0 4.0 4.2 4.2 3.1 3.1 3.2 3.2 3.0 3.0 3.1 3.1 3.6 3.6 3.7 3.7 3.6 3.6 3.8 3.8 3.3 3.3 3.4 3.4 3.5 3.5 3.7 3.7 4.0 4.0 4.2 4.2 3.5 3.5 3.7 3.7 4.1 4.1 4.3 4.3 3.7 3.7 3.9 3.9 3.7 3.7 3.9 3.9 3.4 3.4 3.6 3.6 3.4 3.4 3.7 3.7 3.7 3.7 3.8 3.8 4.2 4.2 4.5 4.5 3.2 3.2 3.3 3.3 3.3 3.3 3.6 3.6 3.5 3.5 3.6 3.6 4.2 4.2 4.3 4.3 3.7 3.7 3.8 3.8 3.9 3.9 4.1 4.1 3.9 3.9 4.0 4.0 3.8 3.8 4.0 4.0 3.1 3.1 3.3 3.3 3.2 3.2 3.3 3.3 3.2 3.2 3.3 3.3 3.4 3.4 3.6 3.6 3.7 3.7 3.8 3.8 Day 51 4.3 3.8 3.6 3.9 4.4 3.9 3.2 3.9 3.9 3.7 4.1 3.4 3.7 4.1 3.6 3.6 4.2 3.2 3.1 3.7 3.8 3.4 3.7 4.2 3.7 4.3 3.9 3.9 3.6 3.7 3.8 4.5 3.3 3.6 3.6 4.3 3.8 4.1 4.0 4.0 3.3 3-3 3.3 3.6 3.8 Day 52 4. 3. 3. 3. 4. 3. 3. 3. 3. 3. 4. 3. 3. 4. 3. 3. 4. 3. 3. 3. 3. 3. 3. 4. 3. 4. 3. 3. 3. 3. 3. 4. 3. 3. 3. 4. 3 4. 4. 4. 3 3 3 3 3 497 Conmny Swi'red. Does not conta H-24516: Subchronic Toxicity 90-Day Gavage Study in Rats with One-Generation Reproduction Evaluations Day 54 Male, I - 0 ing/kg/day 643241 4.3 643300 3.8 643143 3.6 643205 3.9 643235 4.4 643288 3.9 643150 3.2 643189 3.9 643185 3.9 643210 3.7 643268 4.1 643232 3.4 643265 3.7 643239 4.1 643270 3.6 643148 3.6 643284 4.2 643229 3 .2 643196 3.1 643176 3.7 643218 3.8 643207 3.4 643280 3.7 643271 4.2 643211 3.7 643163 4.3 643197 3.9 643242 3.9 643251 3.6 643155 3-7 643147 3.8 643276 4.5 643237 3.3 643226 3.6 643195 3.6 643246 4.3 643253 3.8 643262 4.1 643172 4.0 643303 4.0 643304 3.3 643162 3.3 643254 3.3 64314S 3.6 643204 3.8 Day 55 4 .3 3.8 3.6 3.9 4.4 3.9 3.2 3.9 3.9 3.7 4.1 3 .4 3.7 4.1 3.6 3.6 4.2 3.2 3.1 3.7 3.8 3.4 3.7 4.2 3.7 4.3 3.9 3.9 3.6 3.7 3.8 4.5 3.3 3.6 3.6 4.3 3.8 4.1 4.0 4.0 3.3 3.3 3 .3 3.6 3.8 Day 56 INDIVIDUAL DOSE VOLUME,S Day 57 Day 58 (mL) Day 59 4.4 4.4 4.4 4.4 4.0 4.0 4.0 4.0 3.7 3.7 3.7 3.7 4 . 0 4.0 4.0 4.0 4.5 4.5 4.5 4.5 4.1 4.1 4.1 4.1 3.3 3.3 3.3 3.3 4.1 4.1 4.1 4.1 4.0 4.0 4.0 4.0 3.7 3.7 3.7 3.7 4.2 4.2 4.2 4.2 3.4 3.4 3.4 3.4 3.7 3.7 3.7 3.7 4.2 4.2 4.2 4.2 3 .7 3.7 3.7 3.7 3.7 3.7 3.7 3.7 4.3 4.3 4.3 4.3 3.3 3.3 3.3 3.3 3.2 3.2 3.2 3.2 3.8 3.8 3.8 3.8 4.0 4.0 4.0 4.0 3.5 3.5 3.5 3.5 3.9 3.9 3.9 3.9 4.4 4.4 4.4 4.4 3.8 3.8 3.8 3.8 4.5 4.5 4.5 4.5 4.0 4.0 4.0 4.0 4.1 4,1 4.1 4.1 3.7 3.7 3.7 3.7 4.0 4.0 4.0 4.0 4.0 4.0 4.0 4.0 4.7 4.7 4.7 4.7 3.5 3.5 3.5 3.5 3.7 3.7 3.7 3.7 3.8 3.8 3,8 3.8 4.4 4 .4 4.4 4.4 4.0 4.0 4.0 4.0 4.2 4.2 4.2 4.2 4.3 4.3 4.3 4.3 4.1 4.1 4.1 4.1 3.4 3.4 3.4 3.4 3.1 3.1 3.1 3.1 3.4 3.4 3.4 3.4 3.6 3.6 3.6 3.6 3.9 3.9 3.9 3.9 Day 60 4.4 4.0 3.7 4.0 4.5 4.1 3.3 4.1 4.0 3.7 4.2 3.4 3.7 4.2 3.7 3.7 4.3 3.3 3.2 3.8 4.0 3.5 3.9 4.4 3.8 4.5 4.0 4.1 3.7 4.0 4.0 4.7 3.5 3.7 3.8 4.4 4.0 4.2 4.3 4.1 3.4 3.1 3.4 3 .6 3.9 Day 6 4 4 3 4 4 4 3 4 4 3 4 3 3 4 3 3 4 3 3 3 4 3 3 4 3 4 4 4 3 4 4 4 3 3 3 4 4 4 4 4 3 3 3 498 Company Sanitized. Does nd contai H-24516: Subchronic Toxicity 90-Day Gavage Study in Rats with One-Generation Reproduction Evaluations IIHDIVIDUAL DC3SE VO LUMES (mL) Day 6 3 Male, I - 0 mg/k g/day 643241 643300 643143 643205 643235 643288 643150 643189 643185 643210 643268 643232 643265 643239 643270 643148 643284 643229 643196 643176 643218 643207 643280 643271 643211 643163 643197 643242 643251 643155 643147 643276 643237 643226 643195 643246 643253 643262 643172 643303 643304 643162 643254 643145 643204 4 .6 4 .2 3 .7 4 .1 4 .7 4 .2 3 .5 4 .3 4 .2 3 .8 4 .2 3 .6 3 .7 4.4 3 .8 3 .8 4 .5 3 .4 3 .3 3 .9 4 .1 3 .6 4 .0 4 .6 3 .9 4 .6 4 .2 4 .3 3 .9 4 .1 4 .0 4 .9 3 .6 3 .9 3 .9 4 .6 4 .1 4 .3 4 .4 4 .3 3 .5 3 .0 3 .5 3 .7 4 .1 D ay 6 4 4 .6 4 .2 3 .7 4 .1 4 .7 4 .2 3 .5 4 .3 4 .2 3 .8 4 .2 3 .6 3 .7 4 .4 3 .8 3 .8 4 .5 3 .4 3 .3 3 .9 4 .1 3 .6 4 .0 4 .6 3 .9 4 .6 4 .2 4 .3 3 .9 4 .1 4 .0 4 .9 3 .6 3 .9 3 .9 4 .6 4 .1 4 .3 4 .4 4 .3 3 .5 3 .0 3 .5 3 .7 4 .1 Day 6 5 4 .6 4 .2 3 .7 4 .1 4 .7 4 .2 3 .5 4 .3 4 .2 3 .8 4 .2 3 .6 3 .7 4 .4 3 .8 3 .8 4 .5 3 .4 3 .3 3 .9 4 .1 3 .6 4 .0 4 .6 3 .9 4 .6 4 .2 4 .3 3 .9 4 .1 4 .0 4 .9 3 .6 3 .9 3 .9 4 .6 4 .1 4 .3 4 .4 4 .3 3 .5 3 .0 3 .5 3 .7 4 .1 Day 66 4. 6 4. 2 3. 7 4. 1 4. 7 4. 2 3. 5 4. 3 4. 2 3. 8 4. 2 3. 6 3. 7 4. 4 3. 8 3. 8 4. 5 3. 4 3. 3 3 .9 4. 1 3. 6 4. 0 4. 6 3. 9 4. 6 4 .2 4. 3 3. 9 4. 1 4 0 4 9 3 6 3 9 3 9 4 6 4 1 4 3 4.4 4 3 3 5 3 0 3 5 3 7 4 1 Day 6 7 4 .6 4 .2 3 .7 4 .1 4 .7 4 .2 3 .6 4 .3 4 .2 3 .8 4 .2 3 .6 3 .7 4 .4 3 .8 3 .8 4 .5 3 .4 3 .3 3 .9 4 .1 3 .6 4 .0 4 .6 3 .9 4 .6 4 .2 4 .3 3 .9 4 .1 4 .0 4 .9 3 .6 3 .9 3 .9 4 .6 4 .1 4 .3 4 .4 4 .3 3 .5 3 .0 3 .5 3 .7 4 .1 Day 6 8 4.6 4.2 3.7 4.1 4 .7 4 .2 3.5 4.3 4 .2 3.8 4.2 3.6 3.7 4.4 3.8 3.8 4.5 3.4 3.3 3.9 4.1 3.6 4.0 4.6 3.9 4.6 .2 .3 .9 .1 .0 .9 3.6 3.9 3.9 4.6 4.1 4.3 4.4 4.3 3.5 3.0 3.5 3.7 4.1 Day 6 9 4 .6 4 .2 3 .7 4 .1 4 .7 4 .2 3 .5 4 .3 4 .2 3 .8 4 .2 3 .6 3 .7 4 .4 3 .8 3 .8 4 .5 3 .4 3 .3 3 .9 4 .1 3 .6 4 .0 4 .6 3 .9 4 .6 4 .2 4 .3 3 .9 4 .1 4 .0 4 .9 3 .6 3 .9 3 .9 4 .6 4 .1 4 .3 4 .4 4 .3 3 .5 3 .0 3 .5 3 .7 4 .1 Day 7 0 4 4 3 4 4 4 3 4 4 4. 4 3 3 4 3 3 4 3 3 4 4 3 4 4 4 4 4 4 3 4 4 5 3 4 4 4 4 4 4 4 3 3 3 3 4 499 ^^^^^.Doe.ndlcortaln H-24516: Subchronic Toxicity 90-Day Gavage Study in Rats with One-Generation Reproduction Evaluations Day 72 Male, I - 0 mg/k9/day 643241 643300 643143 643205 643235 643288 643150 643189 643185 643210 643268 643232 643265 643239 643270 643148 6432B4 643229 643196 643176 643218 643207 643280 643271 643211 643163 643197 643242 643251 643155 643147 643276 643237 643226 643195 643246 643253 643262 643172 643303 643304 643162 643254 643145 643204 4 .7 4 .3 3 .8 4 .2 4 .7 4.4 3 .6 4 .4 4 .2 4 .0 4 .4 3 .7 3 .8 4 .5 3 .8 3 .8 4 .7 3 .5 3 .4 4 .0 4 .2 3 .8 4 .2 4 .7 4 .0 4 .8 4 .3 4 .4 3 .9 4 .3 4 .2 5 .1 3 .7 4 .0 4 .1 4 .8 4 .3 4 .4 4 .6 4 .3 31.6 3 .1 31.6 31.8 4i.2 Day 73 4.7 4.3 3.8 4.2 4.7 4.4 3.6 4.4 4.2 4.0 4.4 3.7 3.8 4.5 3.8 3.8 4.7 3.5 3.4 4.0 4.2 3.8 4.2 4.7 4.0 4.8 4.3 4.4 3.9 4.3 4.2 5.1 3.7 4.0 4.1 4.8 4.3 4.4 4.6 4.3 3.6 3.1 3.6 3.8 4.2 Day 74 INDIVIDUAL DOSE VOLUMES Day 75 Day 76 (mL) Day 77 4.7 4.7 4.7 4.7 4.3 4.3 4.3 4.4 3.8 3.8 3.8 3.9 4.2 4.2 4.2 4.3 4.7 4.7 4.7 4.8 4.4 4.4 4.4 4.5 3.6 3.6 3.6 3.6 4.4 4.4 4.4 4.5 4.2 4.2 4.2 4.4 4.0 4.0 4.0 4.0 4.4 4.4 4.4 4.3 3.7 3.7 3.7 3.8 3.8 3.8 3.8 3.8 4.5 3.8 3.8 4.7 3.5 3.4 4.0 4.2 3.8 4.2 4.7 4.0 4.8 4.3 4.4 3.9 4.3 4.2 5.1 3.7 3.7 3.7 3.8 4.0 4.0 4.0 4.1 4.1 4.1 4.1 4.1 4.8 4.8 4.8 4.8 4.3 4.3 4.3 4.3 4.4 4 .4 4.4 4.5 4.6 4.6 4.6 4.7 4.3 4.3 4.3 4.5 3.6 3.6 3.6 3.7 3.1 3.1 3.1 2.8 3.6 3.8 3.8 3.8 3.7 4.2 4.2 4.2 4.2 Day 78 4.7 4.4 3.9 4.3 4.8 4.5 3.6 4.5 4.4 4.0 4.3 3.8 3.8 3.8 4.1 4.1 4.8 4.3 4.5 4.7 4.5 3.7 2.8 3.7 4.2 Day 7 4 3 4 4 4 4 4 4 500 Company SanRhed. Doe) IcoAWn H-24516: Subchronic Toxicity 90-Day Gavage Study in Rats with One-Generation Reproduction Evaluations INDIVIDUAL DOSE VOLUME S (mL) Day 81 Day 82 Day 83 Day 84 Day 85 Day 86 Day 87 Day Male, I - 0 mg/kg/day 643241 4. 7 4.7 4.7 4.9 4.8 4. 8 4.8 643300 4. 4 4.4 4.4 4.5 4.5 4. 5 4.5 643143 3. 9 3.9 3.9 3.9 3.9 3. 9 3.9 643205 4. 3 4.3 4.3 4.4 4.4 4. 4 4.4 643235 4. 8 4.8 4.8 4.9 4.9 4. 9 4.9 643288 4 . 5 4.5 4.5 4.6 4.6 4. 6 4.6 643150 3. 6 3.6 3.6 3.6 3.6 3. 6 3.6 643189 4. 5 4.5 4.5 4.6 4.6 4. 6 4.6 643185 4. 4 4.4 4.4 4.5 4.5 4. 5 4.5 643210 4 .0 4.0 4.0 4.1 4.1 4. 1 4.1 643268 4. 3 4.3 4.3 4.4 4.4 4. 4 4.4 643232 3. 8 3.8 3.8 3.9 3.9 3. 9 3.9 643265 3. 8 3.8 3.8 3.8 3.8 3. 8 3.8 643239 643270 643148 643284 643229 643196 643176 643218 643207 643280 643271 643211 643163 643197 643242 643251 643155 643147 643276 643237 3. 8 3.8 3.8 3.8 3.8 3. 8 3.8 643226 4. 1 4.1 4.1 4.1 4.1 4. 1 4.1 643195 4 .1 4.1 4.1 4.2 4.2 4. 2 4.2 643246 4. 8 4.8 4.8 4.8 4.8 4. 8 4.8 643253 4. 3 4.3 4.3 4.5 4.5 4. 5 4.5 643262 4 .5 4.5 4.5 4.5 4.5 4. 5 4.5 643172 4. 7 4.7 4.7 4.7 4.7 4. 7 4.7 643303 4. 5 4.5 4.5 4.6 4.6 4..6 4.6 643304 3. 7 3.7 3.7 3.8 3.8 3. 8 3.8 643162 2. 8 2.8 2.8 3.0 3.0 3..0 3.0 643254 643145 3. 7 3.7 3.7 3.9 3.9 3.,9 3.9 643204 4. 2 4.2 4.2 4.4 4.4 4.,4 4.4 501 Company Sanitized. Does n H-24516: Subchronic Toxicity 90-Day Gavage Study in Rats with One-Generation Reproduction Evaluations Male, I 643241 643300 643143 643205 643235 643288 643150 643189 643185 643210 643268 643232 643265 643239 643270 643148 643284 643229 643196 643176 643218 643207 643280 643271 643211 643163 643197 643242 643251 643155 643147 643276 643237 643226 643195 643246 643253 643262 643172 643303 643304 643162 643254 643145 643204 Day 90 0 mg/k9/day 4.8 4.5 3.9 4.4 5.0 4.5 3.7 4.7 4.6 4.5 INDIVIDUAL DOSE VOLUMES (mL) 502 Company SanRlzed. Does no H-24516: Subchronic Toxicity 90-Day Gavage Study in Rats with One-Generation Reproduction Evaluations INDIV]:)UAL D0ili VOLUMISi (mL) Day 0 Day 1 Day 2 Day 3 Day 4 Day 5 Day 6 Day 7 Day B Day 9 Day Male, III - 25 mg/kg/day 643173 2.4 2.4 2.4 2.4 2.4 2.4 2.4 3.0 3.0 3.0 643290 2.1 2.1 2.1 2.1 2.1 2.1 2.1 2.7 2.7 2.7 643272 2.3 2.3 2.3 2.3 2.3 2.3 2.3 2.8 2.8 2.8 643232 2.5 2.5 2.5 2.5 2.5 2.5 2.5 3.0 3.0 3.0 643228 2.8 2.8 2.8 2.8 2.8 2.8 2.8 3.5 3.5 3.5 643308 2.6 2.6 2.6 2.6 2.6 2.6 2.6 3.3 3.3 3.3 643264 2.7 2.7 2.7 2.7 2.7 2.7 2.7 3.3 3.3 3.3 643240 2.5 2.5 2.5 2.5 2.5 2.5 2.5 3.0 3.0 3.0 643180 2.4 2.4 2.4 2.4 2.4 2.4 2.4 3.0 3.0 3.0 643179 2.6 2.6 2.6 2.6 2.6 2.6 2.6 3.1 3.1 3.1 643202 2.3 2,3 2.3 C 2.3 2.3 2.3 2.3 2.8 2.8 2.8 643310 2.6 2.6 2.6 C 2.6 2.6 2.6 2.6 3.2 3.2 3.2 643306 2.2 2.2 2.2 C 2.2 2.2 2.2 2.2 2.6 2.6 2.6 643305 2.7 2.7 2.7 C 2.7 2.7 2.7 2.7 3.2 3.2 3.2 643293 2.5 2.5 2.5 C 2.5 2.5 2.5 2.5 3.0 3.0 3.0 643287 2.1 2.1 2.1 2.1 2.1 2.1 2.1 2.6 2.6 2.6 643188 2.6 2.6 2.6 2.6 2.6 2.6 2.6 3.3 3.3 3.3 643230 2.6 2.6 2.6 2.6 2.6 2.6 2.6 3.1 3.1 3.1 643170 2.6 2.6 2.6 2.6 2.6 2.6 2.6 3.2 3.2 3.2 643144 1.9 1.9 1.9 1.9 1.9 1.9 1.9 2.4 2.4 2.4 643277 2.5 2.5 2.5 2.5 2.5 2.5 2.5 3.1 3.1 3.1 643214 2.6 2.6 2.6 2.6 2.6 2.6 2.6 3.3 3.3 3.3 643261 2.6 2.6 2.6 2.6 2.6 2.6 2.6 3.2 3.2 3.2 643166 2.3 2.3 2.3 2.3 2.3 2.3 2.3 2.8 2.8 2.8 643153 2.4 2.4 2.4 2.4 2.4 2.4 2.4 2.9 2.9 2.9 643177 2.4 2.4 2.4 2.4 2.4 2.4 2.4 3.1 3.1 3.1 643198 2.7 2.7 2.7 2.7 2.7 2.7 2.7 3.4 3.4 3.4 643291 2.6 2.6 2.6 2.6 2.6 2.6 2.6 3.2 3.2 3.2 643184 2.4 2.4 2.4 2.4 2.4 2.4 2.4 3.0 3.0 3.0 643167 2.5 2.5 2.5 2.5 2.5 2.5 2.5 3.2 3.2 3.2 643223 2.6 2.6 2.6 2.6 2.6 2.6 2.6 3.1 3.1 3.1 643233 2.4 2.4 2.4 2.4 2.4 2.4 2.4 2.9 2.9 2.9 643183 2.6 2.6 2.6 2.6 2.6 2.6 2.6 3.2 3.2 3.2 643219 2.7 2.7 2.7 2.7 2.7 2.7 2.7 3.3 3.3 3.3 643263 2.3 2.3 2.3 2.3 2.3 2.3 2.3 2.6 2.8 2.8 503 Company Sanitized. Does n H-24516: Subchronic Toxicity 90-Day Gavage Study in Rats with One-Generation Reproduction Evaluations INDIVIDUAL DOSE VOLUMES (mL) Day 12 Day 13 Day 14 Day 15 Day IS Day 17 Day 1B'1 Day 19 Day 20 Day 21 Da Male, III - 25 mg/kg/day 643173 643290 643272 643292 643228 643308 643264 643240 643180 643179 643202 643310 643306 643305 643293 643287 643188 643230 643170 643144 643277 643214 643261 643166 643153 643177 643198 643291 643184 643167 643223 643233 643183 643219 643263 3 .0 2 .7 2 .8 3 .0 3 .5 3 .3 3 .3 3 .0 3 .0 3 .1 2 .8 3 .2 2 .6 3 .2 3 .0 2 .6 3 .3 3 .1 3 .2 2 .4 3 .1 3 .3 3 .2 2 .8 2 .9 3 .1 3 .4 3 .2 3 .0 3 .2 3 .1 2 .9 3 .2 3 .3 2 .8 3. 0 2. 7 2. 8 3. 0 3. 5 3. 3 3. 3 3. 0 3. 0 3. i 2. 8 3. 2 2. 6 3. 2 3 . 0 2. 6 3. 3 3. 1 3. 2 2. 4 3. 1 " 3. 3 3 . 2 2. 8 2. 9 3. 1 3. 4 3 .2 3. 0 3. 2 3. 1 2. 9 3. 2 3. 3 2. 8 3 .5 3 .2 3 .3 3 .5 4 .1 3 .9 3 .9 3 .6 3 .6 3 .7 3 .3 3 .6 3 .0 3 .7 3 .5 3 .0 4 .0 3 .5 3 .7 2 .9 3 .7 3 .7 3 .8 3 .4 3 .5 3 .6 4 .0 3 .8 3 .4 3 .8 3 .6 3 .3 3 .7 3 .8 3 .2 3 .5 3 .2 3 .3 3 .5 4 .1 3 .9 3 .9 3 .6 3 .6 3 .7 3 .3 3 .6 3 .0 3 .7 3 .5 3 .0 4 .0 3 .5 3 .7 2 .9 3 .7 3 .7 3 .8 3 .4 3 .5 3 .6 4 .0 3 .8 3 .4 3 .8 3 .6 3 .3 3 .7 3 .8 3 .2 3 .5 3 .2 3 .3 3 .5 4 .1 3 .9 3 .9 3 .6 3 .6 3 .7 3 .3 3 .6 3 .0 3 .7 3 .5 3 .0 4 .0 3 .5 3 .7 2 .9 3 .7 3 .7 3 .8 . 3 .4 3 .5 3 .6 4 .0 3 .8 3 .4 3 .8 3 .6 3 .3 3 .7 3 .8 3.2 3 .5 3 .2 3 .3 3 .5 4 .1 3 .9 3 .9 3 .6 3 .6 3 .7 3 .3 3 .6 3 .0 3 .7 3 .5 3 .0 4 .0 3 .5 3 .7 2 .9 3 .7 3 .7 3 .8 3 .4 3 .5 3 .6 4 .013 3 .8 3 .4 3 .8 3 .6 3 .3 3 .7 3 .8 3 .2 3 .5 3 .2 3 .3 3 .5 4 .1 3 .9 3 .9 3 .6 3 .6 3 .7 3 .3 3 .6 3 .0 3 .7 3 .5 3 .0 4 .0 3 .5 3 .7 2 .9 3 .7 3 .7 3 .8 3 .4 3 .5 3 .6 4 .0 3 .8 3 .4 3 .8 3 .6 3 .3 3 .7 3 .8 3 .2 3 .5 3 .2 3 .3 3 .5 4 .1 3 .9 3 .9 3 .6 3 .6 3 .7 3 .3 3 .6 3 .0 3 .7 3 .5 3 .0 4 .0 3 .5 3 .7 2 .9 3 .7 3 .7 3 .8 3 .4 3 .5 3 .6 4 .0 3 .8 3 .4 3 .8 3 .6 3 .3 3 .7 3 .8 3 .2 3 .5 3 .2 3 .3 3 .5 4 .1 3 .9 3 .9 3 .6 3 .6 3 .7 3 .3 3 .6 3 .0 3 .7 3 .5 3 .0 4 .0 3 .5 3 .7 2 .9 3 .7 3 .7 3 .8 3 .4 3 .5 3 .6 4 .0 3 .8 3 .4 3 .8 3 .6 3 .3 3 .7 3 .8 3 .2 3 .8 3 .6 3 .5 3 .9 4 .5 4 .2 4 .3 3 .8 4 .0 4 .1 3 .6 4 .1 3 .3 4 .0 3 .9 3 .4 4 .4 3 .8 4 .1 3 .3 4 .2 4 .2 4 .2 3 .7 3 .8 4 .0 4 .5 4 .2 3 .7 4.2 3 .9 3 .6 4 .0 4 .2 3 .6 504 H-24516: Subchronic Toxicity 90-Day Gavage Study in Rats with One-Geperation Reproduction Evaluations INDIVIDUAL DOSE VOLUMES (mL) Day 24 Day 25 Day 26 Day 27 Day 28 Day 29 Day 30 Day 31 Day 32 Day 33 Day Male, III - 25 mg/k9/day 643173 3.8 3.8 3.8 3.8 4.2 4.2 4.2 4.2 4.2 4.2 643290 3.6 3.6 3 .6 3.6 4.0 4.0 4.0 4.0 4.0 4.0 643272 3.5 3.5 3.5 3.5 3.9 3.9 3.9 3.9 3.9 3.9 643292 3.9 3.9 3.9 3.9 4.2 4.2 4.2 4.2 4.2 4.2 643228 4.5 4.5 4.5 4.5 4.9 4.9 4.9 4.9 4.9 4.9 643308 4.2 4.2 4.2 4.2 4.6 4.6 4.6 4.6 4.6 4.6 643264 4.3 4.3 4-3 4.3 4.7 4.7 4.7 4.7 4.7 4.7 643240 3.8 3.8 3.8 3.8 4.1 4.1 4.1 4.1 4.1 4.1 643180 4.0 4.0 4.0 4.0 4.4 4.4 4.4 4.4 4.4 4.4 643179 4.1 4.1 4.1 4.1 4.4 4.4 4.4 4.4 4.4 4.4 643202 3.6 3.6 3.6 3.6 3.8 3.8 3.8 3.8 3.8 3.8 643310 4.1 4.1 4.1 4.1 4.5 4.5 4.5 4.5 4.5 4.5 643306 3.3 3.3 3.3 3.3 3.7 3.7 3.7 3.7 3.7 3.7 643305 4.0 4.0 4.0 4.0 4.2 4.2 4.2 4.2 4.2 .2 643293 3.9 3.9 3.9 3.9 4.2 4.2 4.2 4.2 4.2 .2 6432B7 3.4 3.4 3.4 3.4 3.7 3.7 3,7 3.7 3.7 .7 643188 4.4 4.4 4.4 4.4 4.8 4.8 4.8 4.8 4.8 .8 643230 3.8 3.8 3.8 3.8 4.1 4.1 4.1 4.1 4.1 .1 643170 4.1 4.1 4.1 4.1 4.5 4.5 4.5 4.5 4.5 .5 643144 3.3 3.3 3.3 3.3 3.7 3.7 3.7 3.7 3.7 .7 643277 4.2 4.2 4.2 4.2 4.6 4.6 4.6 4.6 4.6 .6 643214 4.2 - 4.2 4.2 4.2 4.6 4.6 4.6 4.6 4.6 4.6 643261 4.2 4.2 4.2 4.2 4.5 4.5 4.5 4.5 4.5 4.5 643166 3.7 3 .7 3.7 3.7 4.1 4.1 4.1 4.1 4.1 4.1 643153 3.8 3.8 3.8 3.8 4.2 4.2 4.2 4.2 4.2 4.2 643177 4.0 4.0 4.0 4.0 4.4 4.4 4.4 4.4 4.4 4.4 643198 4.5 4.5 4.5 4.5 4.9 4.9 4.9 4.9 4.9 4.9 643291 4.2 4.2 4.2 4.2 4.6 4.6 4.6 4.6 4.6 4.6 643184 3.7 3.7 3.7 3.7 3.8 3.8 3.8 3.8 3.8 3.8 643167 4.2 4.2 4.2 4.2 4.5 4.5 4.5 4.5 4.5 4.5 643223 3.9 3.9 3.9 3.9 4.2 4.2 4.2 4.2 4.2 4.2 643233 3.6 3.6 3.6 3.6 3.8 3.8 3.8 3.8 3.8 3.8 643183 4.0 4.0 4.0 4.0 4.4 4.4 4.4 4.4 4.4 4.4 643219 4.2 4.2 4.2 4.2 4.6 4.6 4.6 4.6 4.6 4.6 643263 3.6 3.6 3.6 3.6 3.9 3.9 3.9 3.9 3.9 3.9 505 ewvswaaiDO' H-24516: Subchronic Toxicity 90-Day Gavage Study in Rats with One-Generation Reproduction Evaluations Day 36 Day 37 Male, III - 25 mg/kg/day 643173 643290 643272 643292 643228 643308 643264 643240 643180 643179 643202 643310 643306 643305 643293 643287 643188 643230 643170 643144 643277 643214 643261 643166 643153 643177 643198 643291 643184 643167 643223 643233 643183 643219 643263 4.7 4 .7 4.3 4 .3 4.1 4 .1 4.6 4 .6 5.4 5 .4 5.0 5 .0 5.0 5 .0 4.3 4 .3 4.8 4 .8 4.6 4 .6 4 .1 4 .1 4.8 4 .8 3.9 3 .9 4.6 4 .6 4 .6 4 .6 4.0 4 .0 5.1 5 .1 4.3 4 .3 4.8 4 .8 3.9 3 .9 4.9 4 .9 4.9 - 4 .9 4.9 4 .9 4.4 4 .4 4.5 4 .5 4.7 4 .7 5.2 5 .2 4.9 4 .9 4.0 4 .0 4.9 4 .9 4.4 4 .4 4.1 4 .1 4.8 4 .8 4.9 4 .9 4.2 4 .2 Day 38 3 .5 3 .2 3 .1 3 .4 4 .1 3 .7 3 .8 3 .3 3 .6 3 .5 3 .1 3 .6 2 .9 3 .4 3 .5 3 .0 3 .8 3 .3 3 .6 2 .9 3 .7 3 .7 3 .7 3 .3 3 .4 3 .6 3 .9 3 .7 3 .0 3 .7 3 .3 3 .1 3 .6 3 .7 3 .1 INDIVIDUAL DOSE VOLUMES (mL) Day 39 Day 40 Day 41 Day 42 3.5 3.5 3.5 3.6 3.2 3.2 3.2 3.5 3.1 3.1 3.1 3.3 3.4 3.4 3.4 3.6 4.1 4.1 4.1 4.2 3.7 3.7 3.7 3.9 3.8 3.8 3.8 4.0 3.3 3.3 3.3 3.3 3.6 3.6 3.6 3.8 3.5 3.5 3.5 3.6 3 .1 3.1 3.1 3.2 3.6 3.6 3.6 3.7 2.9 2.9 2.9 3.1 3.4 3.4 3.4 3.5 3.5 3.5 3 .5 3.6 3.0 3.0 3.0 3.1 3.8 3.8 3.8 3.9 3 .3 3.3 3.3 3.3 3.6 3.6 3.6 3.7 2.9 2.9 2 .9 3.1 3.7 3.7 3.7 3.9 3.7 3.7 3.7 3.8 3.7 3.7 3.7 3.8 3.3 3.3 3.3 3.4 3.4 3.4 3.4 3.5 3.6 3.6 3.6 3.7 3.9 3.9 3.9 4.0 3.7 3.7 3.7 3.9 3.0 3.0 3.0 3.1 3.7 3.7 3.7 3.8 3.3 3.3 3.3 3.5 3.1 3.1 3.1 3.2 3.6 3.6 3.6 3.8 3.7 3.7 3.7 3.8 3.1 3.1 3.1 3.2 Day 43 3.6 3.5 3.3 3.6 4.2 3.9 4.0 3.3 3.8 3.6 3.2 3.7 3.1 3.5 3.6 3.1 3.9 3.3 3.7 3.1 3.9 3.8 3.8 3.4 3.5 3.7 4.0 3.9 3.1 3.8 3.5 3.2 3.8 3.8 3.2 506 Company Sanitized. Doe H-24516: Subchronic Toxicity 90-Day Gavage Study in Rats with One-Generation Reproduction Evaluations Day 45 Day 46 Male, III - 25 mg/kg/day 643173 3.6 3.6 643290 3.5 3.5 643272 3.3 3.3 643292 3.6 3.6 643228 4.2 4.2 643308 3.9 3.9 643264 4.0 4.0 643240 3.3 3.3 643180 3.8 3.8 643179 3.6 3.6 643202 3.2 3.2 643310 3.7 3.7 643306 3.1 3.1 643305 3.5 3.5 643293 3.6 3.6 643287 3.1 3.1 643188 3.9 3.9 643230 3.3 3.3 643170 3.7 3.7 643144 3.1 3.1 643277 3.9 3.9 643214 3.8 3.8 643261 3.8 3.8 643166 3.4 3.4 643153 3.5 3.5 643177 3.7 3.7 643198 4.0 4.0 643291 3.9 3.9 643184 3.1 3.1 643167 3.8 3.8 643223 3.5 3.5 643233 3.2 3.2 643183 3.8 3.8 643219 3.8 3.8 643263 3.2 3.2 Day 47 INDIV IDUA]L. D OSE VOLUME S Day 48 Day 49 (mL) Day 50 3.6 3.6 3.7 3.7 3.5 3.5 3.5 3.5 3.3 3.3 3.3 3.3 3.6 3.6 3.7 3.7 4.2 4.2 4.3 4.3 3.9 3.9 4.0 4.0 4.0 4.0 4.0 4.0 3.3 3.3 3.3 3.3 3.8 3.8 3.9 3.9 3.6 3.6 3.6 3.6 3.2 3.2 3.4 3.4 3.7 3.7 3.8 3.8 3.1 3.1 3.1 3.1 3.5 3.5 3.7 3.7 3 .6 3.6 3.7 3.7 3.1 3.1 3.2 3.2 3.9 3.9 4.1 4.1 3.3 3 .3 3.5 3.5 3 .7 3.7 3.8 3.8 3.1 3.1 3.2 3.2 3.9 3.9 4.0 4.0 3.8 3.8 3.8 3.8 3.8 3.8 3.9 3.9 3.4 3.4 3.6 3.6 3.5 3.5 3.5 3.5 3.7 3.7 3.9 3.9 4.0 4.0 4.2 4.2 3.9 3.9 4.0 4.0 3.1 3.1 3.2 3.2 3.8 3.8 3.8 3.8 3.5 3.5 3.6 3.6 3.2 3.2 3.2 3.2 3.8 3.8 4.0 4.0 3.8 3.8 4.0 4.0 3.2 3.2 3.4 3.4 Day 51 3.7 3.5 3.3 3.7 4.3 4.0 4.0 3.3 3.9 3.6 3.4 3.8 3.1 3.7 3.7 3.2 4.1 3.5 3.8 3.2 4.0 3.8 3.9 3.6 3.5 3.9 4.2 4.0 3.2 3.8 3.6 3.2 4.0 4.0 3.4 Day 5 3 3 3 3 4 4 4 3 3 3 3 3 3 3 3 3 4 3 3 3 4 3 3 3 3 3 4 4 3 3 3 3 4 4 3 507 CBHI'>" 8n'CTed. Does no H-24516: Subchronic Toxicity 90-Day Gavage Study in Rats with One-Generation Reproduction Evaluations INDIVIDUAL DOSE VOLUMES (mL) Day 54 Day 55 Day 56 Day 57 Day 58 Day 59 Day 60 Day Male, III - 25 mg/kg/day 643173 3 .7 3.7 3.8 3.8 3.8 3.8 3.8 643290 3 .5 3.5 3.8 3.8 3.8 3.8 3.8 643272 3 .3 3.3 3.4 3.4 3.4 3.4 3.4 643292 3 .7 3.7 3.8 3.8 3.8 3.8 3.8 643228 4 .3 4.3 4.5 4.5 4.5 4.5 4.5 643308 4 .0 4.0 4.1 4.1 4.1 4.1 4.1 643264 4 .0 4.0 4.2 4.2 4.2 4.2 4.2 643240 3 .3 3.3 3.4 3-4 3.4 3.4 3.4 643180 3 .9 3.9 4.0 4.0 4.0 4.0 4.0 643179 3 .6 3.6 3.7 3.7 3.7 3.7 3.7 643202 3 .4 3.4 3.3 3.3 3.3 3.3 3.3 643310 3 .8 3.8 3.9 3.9 3.9 3.9 3.9 643306 3 .1 3.1 3.2 3.2 3.2 3.2 3-2 643305 3 .7 3.7 3.7 3.7 3.7 3.7 3.7 643293 3 .7 3.7 3.9 3.9 3.9 3.9 3.9 643287 3 .2 3.2 3.3 3.3 3.3 3.3 3.3 643188 4 .1 4.1 4.4 4.4 4.4 4.4 4.4 643230 3 .5 3.5 3.6 3.6 3.6 3.6 3.6 643170 3 .8 3 .8 3.9 3.9 3-9 3.9 3.9 643144 3 .2 3.2 3.3 3.3 3.3 3.3 3.3 643277 4 .0 4.0 4.1 4.1 4.1 4.1 4.1 643214 3 .8 3.8 4.0 4.0 4.0 4.0 4.0 643261 3 .9 3.9 4.1 4.1 4.1 4.1 4.1 643166 3 .6 3.6 3.8 3.8 3.8 3.8 3.8 643153 3 .5 3.5 3.7 3-7 3.7 3.7 3.7 643177 3 .9 3.9 4.0 4.0 4.0 4.0 4.0 643198 4 .2 4.2 4.4 4.4 4.4 4.4 4.4 643291 4 .0 4.0 4.1 4.1 4.1 4.1 4.1 643184 3 .2 3.2 3.3 3.3 3.3 3.3 3.3 643167 3 .8 3.8 3.9 3.9 3.9 3.9 3.9 643223 3 .6 3.6 3.7 3.7 3.7 3.7 3.7 643233 3 .2 3.2 2.9 2.9 2.9 2.9 2.9 643183 4 .0 4.0 4.1 4.1 4.1 4.1 4.1 643219 4 .0 4.0 4.1 4.1 4.1 4.1 4.1 643263 3 .4 3.4 3.5 3.5 3.5 3.5 3.5 508 Company SanRtzed. Does n H-24516: Subchronic Toxicity 90-Day Gavage Study in Rats with One-Generation Reproduction Evaluations Day 63 Day 64 Male, III - 25 mg/kg/day 643173 3 .9 3.9 643290 3 .9 3.9 643272 3 .7 3.7 643292 3 .9 3.9 643228 4 .7 4.7 643308 4 .2 4.2 643264 4.4 4.4 643240 3 .5 3.5 643180 4 .2 4.2 643179 3 .7 3.7 643202 3 .4 3.4 643310 4 .0 4.0 643306 3 .2 3.2 643305 3 .8 3.8 643293 4 .1 4.1 643287 3 .4 3.4 643188 4 .5 4.5 643230 3 .7 3.7 643170 4 .1 4.1 643144 3 .4 3 .4 643277 4.4 4.4 643214 4 .1 4.1 643261 4 .3 4.3 643166 3 .9 3.9 643153 3 .8 3.8 643177 4 .1 4.1 643198 4 .4 4.4 643291 4 .3 4.3 643184 3 .2 3.2 643167 4 .0 4.0 643223 3 .8 3.8 643233 3 .3 3.3 643183 4 .2 4.2 643219 4 .3 4.3 643263 3 .6 3.6 Day 65 INDIVIDUAL DOSE VOLUMES Day 66 Day 67 (mL) Day 68 3.9 3.9 3.9 3.9 3.9 3.9 3.9 3.9 3.7 3.7 3.7 3.7 3.9 3.9 3.9 3.9 4.7 4.7 4.7 4.7 4.2 4.2 4.2 4.2 4.4 4.4 4.4 4.4 3.5 3.5 3.5 3.5 4.2 4.2 4.2 4.2 3.7 3.7 3.7 3.7 3.4 3.4 3.4 3.4 4.0 4.0 4.0 4.0 3.2 3.2 3.2 3.2 3.8 3.8 3.8 3.8 4.1 4.1 4.1 4.1 3.4 3.4 3.4 3.4 4.5 4.5 4.5 4.5 3.7 3 .7 3 .7 3.7 4 .1 4.1 4.1 4.1 3.4 3.4 3.4 3.4 4.4 4.4 4.4 4.4 4.1 4.1 4.1 4.1 4.3 4.3 4.3 4.3 3.9 3.9 3.9 3.9 3.8 3.8 3.8 3.8 4.1 4.1 4.1 4.1 4.4 4.4 4.4 4.4 4.3 4.3 4.3 4.3 3.2 3.2 3.2 3.2 4.0 4.0 4.0 4.0 3.8 3.8 3.8 3.8 3.3 3.3 3.3 3.3 4.2 4.2 4.2 4.2 4.3 4.3 4.3 4.3 3.6 3.6 3.6 3.6 Day 69 3.9 3.9 3.7 3.9 4.7 4.2 4.4 3.5 4.2 3.7 3.4 4.0 3.2 3.8 4.1 3.4 4.5 3.7 4.1 3.4 4.4 4.1 4.3 3.9 3.8 4.1 4.4 4.3 3.2 4.0 3.8 3.3 4.2 4.3 3.6 Day 4 4 4 4 4 509 Company Sanfflzed. Does not con H-24516: Subchronic Toxicity 90-Day Gavage Study in Rats with One-Generation Reproduction Evaluations INDIVIDUAL DOSE VOLUMES (mL) Day 72 Day 73 Day 74 Day 75 Day 76 Day 77 Day 78 Day Male, III - 25 mg/kg/day 643173 4 .0 4.0 4.0 4.0 4.0 4.1 4.1 643290 4 .0 4.0 4.0 4.0 4.0 4.1 4.1 643272 3 .8 3.8 3.8 3.8 3.8 3.9 3.9 643292 4 .0 4.0 4.0 4.0 4.0 4.0 4.0 643228 4 .8 4.8 4.8 4.8 4.8 5.0 5.0 643308 4 .4 4.4 4.4 4.4 4.4 4.5 4.5 643264 4 .5 4.5 4.5 4.5 4.5 4.7 4.7 643240 3 .6 3.6 3.6 3.6 3.6 3.7 3.7 643180 4 .1 4.1 4.1 4.1 4.1 4.2 4.2 643179 3 .9 3.9 3.9 3.9 3.9 3.9 3.9 643202 3 .4 3.4 3.4 3.4 3.4 3.5 3.5 643310 4 .2 4.2 4.2 4.2 4.2 4.1 4.1 643306 3 .3 3.3 3.3 3.3 3.3 3.3 3.3 643305 4 .0 4.0 4.0 4.0 4 .0 4.0 4.0 643293 4 .2 4.2 4.2 4.2 4.2 4.1 4.1 643287 3 .5 3.5 3.5 643188 4 .6 4.6 4.6 643230 3 .7 3.7 3.7 643170 4 .2 4.2 4.2 643144 3 .6 3.6 3.6 643277 4 .5 4.5 4.5 643214 4 .2 4.2 4.2 643261 4.4 4.4 4.4 643166 4 .1 4.1 4.1 643153 3 ,9 3.9 3.9 643177 4 .2 4.2 4.2 643198 4 .5 4.5 4.5 643291 4 .4 4.4 4.4 643184 3 .3 3.3 3.3 643167 4 .2 4.2 4.2 643223 3 .9 3.9 3.9 643233 3 .5 3.5 3.5 643183 4 .3 4.3 4.3 643219 4 .4 4.4 4.4 643263 3 .7 3.7 3.7 510 Company Sanffized. Does n ^ir H-24516: Subchronic Toxicity 90-Day Gavage Study in Rats with One-Generation Reproduction Evaluations INDIVIDUAL DOSE VOLUMES (mL) Day 81 Day 82 Day 83 Day 84 Day 85 Day 86 Day 87 Day Male, III - 25 mg/kg/day 643173 4.1 4.1 4.1 4.1 4.1 4.1 4.1 643290 4.1 4-1 4.1 4.2 4.2 4.2 4.2 643272 3.9 3.9 3.9 4.0 4.0 4.0 4.0 643292 4.0 4.0 4.0 4.0 4.0 4.0 4.0 643228 5.0 5.0 5.0 5.1 5.1 5.1 5.1 64330B 4.5 4.5 4.5 4.7 4.7 4.7 4.7 643264 4.7 4.7 4.7 4.8 4.8 4.8 4.8 643240 3.7 3.7 3.7 3.7 3.7 3.7 3.7 643180 4.2 4.2 4.2 4.3 4.3 4.3 4.3 643179 3.9 3.9 3.9 4.1 4.1 4.1 4,1 643202 3.5 3.5 3.5 3.5 3.5 3.5 3.5 643310 4.1 4.1 4.1 4 .2 4.2 4.2 4.2 643306 3.3 3.3 3.3 3.5 3.5 3.5 3.5 643305 4.0 4.0 4.0 4.1 4.1 4.1 4.1 643293 4.1 4.1 4.1 4.2 4.2 4.2 4.2 643287 643188 643230 643170 643144 643277 643214 643261 643166 643153 643177 643198 643291 643184 643167 643223 643233 643183 643219 643263 511 Company Sanitized. Doe* w H-24516: Subchronic Toxicity 90-Day Gavage Study in Rats with One-Generation Reproduction Evaluations Day 90 Male, III - 643173 643290 643272 643292 643228 643308 643264 643240 643180 643179 643202 643310 643306 643305 643293 643287 643188 643230 643170 643144 643277 643214 643261 643166 643153 643177 643198 643291 643184 643167 643223 643233 643183 643219 643263 25 ing/kg/day 3.9 4.3 4.1 4.1 5.2 4.7 4.9 3.8 4.3 4.1 INDIVIDUAL DOSE VOLUMES (mL) 512 Comoanv S"''ed. Does nol H-24516: Subchronic Toxicity 90-Day Gavage Study in Rats with One-Generation Reproduction Evaluations INDIVI:r)UAL DOSili VOLUME!i (mL) Day 0 Day 1 Day 2 Day 3 Day 4 Day 5 Day 6 Day 7 Day 8 Day 9 Day Male, V - 100 mg/kg/day 643250 2.3 2.3 2.3 2.3 2.3 2.3 2.3 2.8 2.8 2.8 643243 2.3 2.3 2.3 2.3 2.3 2.3 2.3 2.9 2.9 2.9 643311 2.4 2.4 2.4 2.4 2.4 2.4 2.4 3.0 3.0 3.0 64331B 2.6 2.6 2.6 2.6 2-6 2.6 2.6 3.2 3.2 3.2 643247 2.8 2.8 2.8 2.8 2.8 2.8 2.8 3.5 3.5 3.5 643175 2.6 2.6 2.6 2.6 2.6 2.6 2.6 3.2 3.2 3.2 643314 2.6 2.6 2.6 2.6 2.6 2.6 2.6 3.3 3.3 3.3 643275 2.7 2.7 2.7 2.7 2.7 2.7 2.7 3.2 3.2 3.2 643257 2.4 2.4 2.4 2.4 2.4 2.4 2.4 3.0 3.0 3.0 643224 2.5 2.5 2.5 2.5 2.5 2.5 2.5 3.0 3.0 3.0 643169 2.3 2.3 2.3 2.3 2.3 2.3 2.3 2.8 2.8 2.8 643159 2.7 2.7 2.7 2.7 2.7 2.7 2.7 3.1 3.1 3.1 643286 2.1 2.1 2.1 2.1 2.1 2.1 2.1 2.5 2.5 2.5 643181 2.8 2.8 2.8 2.8 2.8 2.8 2.8 3.3 3.3 3.3 643206 2.4 2.4 2.4 2.4 2.4 2.4 2.4 2.9 2.9 2.9 643313 2.1 2.1 2.1 2.1 2.1 2.1 2.1 2.7 2.7 2.7 643182 2.5 2.5 2.5 2.5 2.5 2.5 2.5 3.1 3.1 3.1 643146 2.8 2 .8 2.8 2.8 2.8 2.8 2.8 3.3 3.3 3.3 643312 2.4 2.4 2.4 2.4 2.4 2.4 2.4 3.0 3.0 3.0 643199 2.4 2.4 2.4 2.4 2.4 2.4 2.4 3.1 3.1 3.1 643267 2.5 2.5 2.5 2.5 2.5 2.5 2.5 3.1 3.1 3.1 643216 2.7 2.7 2.7 2.7 2.7 2.7 2.7 3.4 3.4 3.4 643244 2.5 2.5 2.5 2.5 2.5 2.5 2.5 3.0 3.0 3.0 643245 2.3 2.3 2.3 2.3 2.3 2.3 2.3 2.8 2.8 2.8 643301 2.6 2.6 2.6 2.6 2.6 2.6 2.6 3.1 3.1 3.1 643200 2.4 2.4 2.4 2.4 2.4 2.4 2.4 3.1 3.1 3.1 643255 2.6 2.6 2.6 2.6 2.6 2.6 2.6 3.1 3.1 3.1 643157 2.4 2.4 2.4 2.4 2.4 2.4 2.4 3.0 3.0 3.0 643238 2.6 2.6 2.6 2.6 2.6 2.6 2.6 3.1 3.1 3.1 643227 2.6 2.6 2.6 2.6 2.6 2.6 2.6 3.3 3.3 3.3 643164 2.5 2.5 2.5 2.5 2.5 2.5 2.5 3.3 3.3 3.3 643154 2.4 2.4 2.4 2.4 2.4 2.4 2.4 3.0 3.0 3.0 643156 2.7 2.7 2.7 2.7 2.7 2.7 2.7 3.3 3.3 3.3 643208 2.5 2.5 2.5 2.5 2.5 2.5 2.5 3.0 3.0 3.0 643190 2.7 2.7 2.7 2.7 2.7 2.7 2.7 3.3 3.3 3.3 513 Company Smithed. Do ~\jsy H-24516: Subchronic Toxicity 90-Day Gavage Study in Rats with One-Generation Reproduction Evaluations INDIVI:r)UAL DOEiti VOLUMEiS (mL) Day 12 Day 13 Day 14 Day 15 Day 16 Day 17 Day 18 Day 19 Day 20 Day 21 Day Male, V - 100 ing/kg/day 643250 2.8 2.8 3.1 3.1 3.1 3.1 3.1 3.1 3.1 3.5 643243 2.9 2.9 3.5 3.5 3.5 3.5 3.5 3.5 3.5 3.9 643311 3.0 3.0 3.6 3.6 3-6 3.6 3.6 3.6 3-6 3.9 643318 3.2 3.2 3.7 3.7 3.7 3.7 3.7 3.7 3.7 4.3 643247 3.5 3.5 4.1 4.1 4.1 4.1 4.1 4.1 4.1 4.5 643175 3.2 3 .2 3.7 3.7 3.7 3.7 3.7 3.7 3.7 4.2 643314 3.3 3.3 3.7 3.7 3.7 3.7 3.7 3.7 3.7 4.1 643275 3.2 3.2 3.7 3.7 3.7 3.7 3.7 3.7 3.7 4.1 643257 3.0 3-0 3.5 3.5 3.5 3.5 3.5 3.5 3.5 3.9 643224 3.0 3.0 3.4 3.4 3.4 3.4 3.4 3.4 3.4 3.7 643169 2.8 2.8 3.3 3.3 3.3 3.3 3.3 3.3 3.3 3.7 643159 3.1 3.1 3.6 3.6 3.6 3.6 3.6 3.6 3.6 3.9 643286 2.5 2.5 2.9 2.9 2.9 2.9 2.9 2.9 2.9 3.3 643181 3.3 3.3 3.8 3.8 3.8 3.8 3.8 3.8 3.8 4.1 643206 2.9 2.9 3.2 3.2 3.2 3.2 3.2 3.2 3.2 3.7 643313 2.7 2.7 3.2 3.2 3.2 3.2 3.2 3.2 3.2 3.6 643182 3.1 3.1 3.7 3.7 3.7 3.7 3.7 3.7 3.7 4.2 643146 3.3 3.3 3.7 3.7 3.7 3.7 3.7 3.7 3.7 4.2 643312 3.0 3.0 3.5 3.5 3.5 3.5 3.5 3.5 3-5 3.8 643199 3.1 3.1 3.7 3.7 3.7 3.7 3.7 3.7 3.7 4.2 643267 3.1 3.1 3.7 3.7 3.7 3.7 3.7 3.7 3.7 4.2 643216 3.4 3.4 4.0 4.0 4.0 4.0 4.0 4.0 4.0 4.5 643244 3.0 3.0 3.6 3.6 3.6 3.6 3.6 3.6 3.6 3.9 643245 2.8 2.8 3.1 3.1 3.1 3.1 3.1 3.1 3.1 3.5 643301 3.1 3.1 3.6 3.6 3.6 3.6 3.6 3.6 3.6 4.0 643200 3.1 3.1 3.6 3.6 3.6 3.6 3.6 3.6 3.6 4.0 643255 3.1 3.1 3.7 3.7 3.7 3.7 3.7 3.7 3.7 4.2 643157 3.0 3.0 3.5 3.5 3.5 3.5 3.5 3.5 3.5 3.9 643238 3.1 3.1 3.5 3.5 3.5 3.5 3.5 3.5 3.5 4.0 643227 3.3 3.3 3.8 3.8 3.8 3.8 3.8 3.8 3.8 4.1 643164 3.3 3.3 3.8 3.8 3.8 3.8 3.8 3.8 3.8 4.3 643154 3.0 3.0 3.4 3.4 3.4 3.4 3.4 3.4 3.4 3.9 643156 3.3 3.3 3.8 3.8 3.8 3.8 3.8 3.8 3.8 4.3 643208 3.0 3.0 3.5 3.5 3.5 3.5 3.5 3.5 3.5 3.9 643190 3.3 3.3 3.8 3.8 3.B 3.8 3.8 3.8 3.8 4.2 514 eampHf Sanitized. Doe* H-24516; Subchronic Toxicity 90-Day Gavage Study in Rats with One-Generation Reproduction Evaluations INDIV][1)UAL DOS31S VOLUMI3S (mL) Day 24 Day 25 Day 26 Day 27 Day 28 Day 29 Day 30 Day 31 Day 32 Day 33 Day Male, V - 100 mg/kg/day 643250 3.5 3.5 3.5 3.5 3.9 3.9 3.9 3.9 3.9 3.9 643243 3.9 3.9 3.9 3.9 4.2 4.2 4.2 4.2 4.2 4.2 643311 3.9 3.9 3.9 3.9 4.2 4.2 4.2 4.2 4.2 4.2 643318 4.3 4.3 4.3 4.3 4.6 4.6 4.6 4.6 4.6 4.6 643247 4.5 4.5 4.5 4.5 4.8 4.8 4.8 4.8 4.8 4.8 643175 4.2 4.2 4.2 4.2 4.5 4.5 4.5 4.5 4.5 4.5 643314 4.1 4.1 4.1 4.1 4.3 4.3 4.3 4.3 4.3 4.3 643275 4.1 4.1 4.1 4.1 4.5 4.5 4.5 4.5 4.5 4.5 643257 3.9 3.9 3.9 3.9 4.1 4.1 4.1 4.1 4.1 4.1 643224 3.7 3.7 3.7 3.7 4.0 4.0 4.0 4.0 4.0 4.0 643169 3.7 3.7 3 .7 3.7 4.0 4.0 4.0 4.0 4.0 4.0 643159 3.9 3.9 3.9 3.9 4.3 4.3 4.3 4.3 4.3 4.3 643286 3.3 3.3 3.3 3.3 3.6 3.6 3.6 3.6 3.6 3.6 643181 4.1 4.1 4.1 4.1 4.4 4.4 4.4 4.4 4.4 4.4 643206 3.7 3.7 3.7 3.7 3.8 3.8 3.8 3.8 3.8 3.8 643313 3.6 3.6 3.6 3.6 3.9 3.9 3.9 3.9 3.9 3.9 643182 4.2 4.2 4.2 4.2 4.6 4.6 4.6 4.6 4.6 4.6 643146 4.2 4.2 4.2 4.2 4.5 4.5 4.5 4.5 4 .5 4.5 643312 3.8 3.8 3.8 3.8 4.0 4.0 4.0 4.0 4.0 4.0 643199 4.2 4.2 4.2 4.2 4.7 4.7 4.7 4.7 4.7 4.7 643267 4.2 4.2 4.2 4.2 4.5 4.5 4.5 4.5 4.5 4.5 643216 4.5 4.5 4.5 4.5 4.9 4.9 4.9 4.9 4.9 4.9 643244 3.9 3.9 3.9 3.9 4.3 4 .3 4.3 4.3 4.3 4.3 643245 3.5 3.5 3.5 3.5 3.8 3.8 3.8 3.8 3.8 3.8 643301 4.0 4.0 4.0 4.0 4.4 4.4 4.4 4.4 4.4 4.4 643200 4.0 4.0 4.0 4.0 4.4 4.4 4.4 4 .4 4.4 4.4 643255 4.2 4.2 4.2 4.2 4.6 4.6 4.6 4.6 4.6 4.6 643157 3.9 3.9 3.9 3-9 4.2 4.2 4.2 4.2 4.2 4.2 643238 4.0 4.0 4.0 4.0 4.1 4.1 4.1 4.1 4.1 4.1 643227 4.1 4.1 4.1 4.1 4.5 4-5 4.5 4.5 4.5 4.5 643164 4.3 4.3 4.3 4.3 4.7 4.7 4.7 4.7 4.7 4.7 643154 3.9 3.9 3.9 3.9 4.2 4.2 4.2 4.2 4.2 4.2 643156 4.3 4.3 4.3 4.3 4.7 4 .7 4.7 4.7 4.7 4.7 643208 3.9 3.9 3.9 3.9 4.1 4.1 4.1 4.1 4.1 4.1 643190 4.2 4.2 4.2 4.2 4.5 4.5 4.5 4.5 4.5 4.5 515 Company SanfBzad.Dow no /- , '^_/ H-24516: Subchronic Toxicity 90-Day Gavagc Study in Rats with One-Generation Reproduction Evaluations Day 36 Day 37 Male, V - 100 ing/kg/day 643250 643243 643311 643318 643247 643175 643314 643275 643257 643224 643169 643159 643286 643181 643206 643313 643182 643146 643312 643199 643267 643216 643244 643245 643301 643200 643255 643157 643238 643227 643164 643154 643156 643208 643190 4 .0 4 .5 4 .4 4 .9 5 .0 4 .8 4 .5 4 .7 4.4 4 .2 4 .2 4 .7 3 .9 4 .6 4 .0 4 .2 5 .0 4 .8 4 .2 4 .8 4 .8 5 .2 4 .5 3 .9 4 .7 4 .7 4 .8 4 .5 4 .3 4 .7 5 .0 4 .4 4 .9 4 .3 4 .8 5 .9 4 .5 4 .4 4 .9 5 .0 4 .8 4 .5 4 .7 4.4 4 .2 4 .2 4 .7 3 .9 4 .6 4 .0 4 .2 5 .0 4 .8 4 .2 4 .8 4 .8 5 .2 4 .5 3 .9 4 .7 4 .7 4 .8 4 .5 4 .3 4 .7 5 .0 4 .4 4 .9 4 .3 4 .8 Day 38 3.0 3.4 3.3 3.7 3.7 3.6 3.4 3.5 3.3 3.2 3.2 3.5 2.9 3.5 3.0 3.2 3.7 3.6 3.1 3.6 3.6 3.9 3.4 2.9 3.5 3.5 3.6 3.4 3.3 3.5 3.7 3.3 3.7 3.3 3.6 INDIVIDUAL DOSE VOLUMES (mL) Day 39 Day 40 Day 41 Day 42 3.0 3.0 3.0 3.1 3.4 3.4 3.4 3.5 3 .3 3.3 3.3 3.5 3.7 3.7 3.7 3.8 3.7 3.7 3.7 3.9 3.6 3.6 3.6 3.8 3.4 3.4 3.4 3.6 3.5 3.5 3.5 3.7 3.3 3.3 3.3 3.4 3.2 3.2 3.2 3.3 3.2 3.2 3.2 3.3 3.5 3.5 3.5 3.6 2.9 2.9 2.9 3.1 3.5 3.5 3.5 3.7 3.0 3.0 3.0 3.1 3.2 3.2 3.2 3.3 3.7 3.7 3.7 3.9 3.6 3.6 3.6 3.7 3.1 3.1 3.1 3.2 3.6 3.6 3.6 3.7 3.6 3.6 3.6 3.8 3.9 3.9 3.9 4.1 3.4 3.4 3.4 3.5 2.9 2.9 2.9 3.0 3.5 3.5 3.5 3.6 3.5 3.5 3.5 3.7 3.6 3.6 3.6 3.8 3.4 3.4 3.4 3.6 3.3 3.3 3.3 3.5 3.5 3.5 3.5 3.8 3.7 3.7 3.7 3.9 3.3 3.3 3.3 3.4 3.7 3.7 3.7 3.9 3.3 3.3 3.3 3.4 3.6 3.6 3.6 3.8 Day 43 3.1 3.5 3.5 3.8 3.9 3.8 3.6 3.7 3.4 3.3 3.3 3.6 3.1 3.7 3.1 3.3 3.9 3.7 3.2 3.7 3.8 4.1 3.5 3.0 3.6 3.7 3.8 3.6 3.5 3.8 3.9 3.4 3.9 3.4 3.8 516 Doe* H-24516: Subchronic Toxicity 90-Day Gavage Study in Rats with One-Generation Reproduction Evaluations Male, V - 643250 643243 643311 643318 643247 643175 643314 643275 643257 643224 643169 643159 643286 643181 643206 643313 643182 643146 643312 643199 643267 643216 643244 643245 643301 643200 643255 643157 643238 643227 643164 643154 643156 643208 643190 Day 45 100 nig/kg/day 3 .1 3 .5 3 .5 3 .8 3 .9 3 .8 3 .6 3 .7 3 .4 3 .3 3 .3 3 .6 3 .1 3 .7 3 .1 3 .3 3 .9 3 .7 3 .2 3 .7 3 .8 4 .1 3 .5 3 .0 3 .6 3 .7 3 .8 3 .6 3 .5 3 .8 3 .9 3 .4 3 .9 3 .4 3 .8 Day 46 3.1 3.5 3.5 3.8 3.9 3.8 3.6 3.7 3.4 3.3 3.3 3.6 3.1 3.7 3.1 3.3 3.9 3.7 3.2 3.7 3.8 4.1 3.5 3.0 3.6 3.7 3.B 3.6 3.5 3.8 3.9 3.4 3.9 3.4 3.8 Day 47 INDIVIDUAL DOSE VOLUMES (mL) Day 48 Day 49 Day 50 3.1 3.1 3.2 3.2 3.5 3.5 3.6 3.6 3.5 3.5 3.6 3.6 3.8 3.8 3.9 3.9 3.9 3.9 3.6 3.6 3.8 3.8 3.8 3.8 3.6 3.6 3.7 3.7 3.7 3.7 3.8 3.8 3.4 3.4 3.4 3.4 3.3 3.3 3.3 3.3 3.3 3.3 3.4 3.4 3.6 3.6 3.7 3.7 3.1 3.1 3.3 3.3 3.7 3.7 3.9 3.9 3.1 3.1 3.3 3.3 3 .3 3.3 3.5 3.5 3.9 3.9 4.0 4.0 3.7 3 .7 3.8 3.8 3.2 3.2 3.3 3.3 3.7 3.7 3.8 3.8 3.8 3.8 4.0 4.0 4.1 4.1 4.2 4.2 3.5 3.5 3.7 3.7 3.0 3.0 3.1 3.1 3.6 3.6 3.8 3.8 3.7 3.7 3.8 3.8 3.8 3.8 4.0 4.0 3.6 3.6 3.8 3.8 3.5 3.5 3.7 3.7 3.8 3.8 4.0 4.0 3.9 3.9 4.1 4.1 3.4 3.4 3.6 3.6 3.9 3.9 4.1 4.1 3.4 3.4 3.6 3.6 3.8 3.8 3.9 3.9 Day 51 3.2 3.6 3.6 3.9 3.6 3.8 3.7 3.8 3.4 3.3 3.4 3.7 3.3 3.9 3.3 3.5 4.0 3.8 3.3 3.8 4.0 4.2 3.7 3.1 3.8 3.8 4.0 3.8 3.7 4.0 4.1 3.6 4.1 3.6 3.9 Day 5 3 3 3 3 3 3 3 "517 Company Santtlzed. Does not co H-24516: Subchronic Toxicity 90-Day Gavage Study in Rats with One-Generation Reproduction Evaluations INDIVIDUAL DOSE VOLUMES (mL) Day 54 Day 55 Day 56 Day 57 Day 58 Day 59 Day 60 Day Male, V - 100 mg/k9/day 643250 3 .2 3.2 3.3 3.3 3.3 3.3 3.3 643243 3 .6 3.6 3.7 3.7 3.7 3.7 3.7 643311 3 .6 3.6 3.6 3.6 3.6 3.6 3.6 643318 3 .9 3.9 4.0 4.0 4.0 4.0 4.0 643247 3 .6 3.6 3.8 3.8 3.8 3.8 3.8 643175 3 .8 3.8 4.0 4.0 4.0 4.0 4.0 643314 3 .7 3.7 3.8 3.B 3.8 3.8 3.8 643275 3 .8 3.8 3.9 3.9 3.9 3.9 3.9 643257 3 .4 3.4 3.6 3.6 3.6 3.6 3.6 643224 3 .3 3.3 3.4 3.4 3.4 3-4 3.4 643169 3 .4 3.4 3.4 3.4 3.4 3.4 3.4 643159 3 .7 3.7 3.9 3.9 3.9 3.9 3.9 643286 3 .3 3.3 3.4 3.4 3.4 3.4 3.4 643181 3 .9 3.3 4.0 4.0 4.0 4.0 4.0 643206 3 .3 3.3 3.3 3.3 3.3 3.3 3.3 643313 3 .5 3.5 3.6 3.6 3.6 3.6 3.6 643182 4 .0 4.0 4.1 4.1 4.1 4.1 4.1 643146 3 .8 3.8 4 .0 4.0 4.0 4.0 4.0 643312 3 .3 3.3 3.5 3.5 3.5 3.5 3.5 643199 3 .8 3.8 3.9 3.9 3.9 3.9 3.9 643267 4 .0 4.0 4.0 4.0 4.0 4.0 4.0 643216 4 .2 4.2 4.3 4.3 4-3 4.3 4.3 643244 3 .7 3.7 3.7 3.7 3.7 3.7 3.7 643245 3 .1 3.1 3.3 3.3 3.3 3.3 3.3 643301 3 .8 3.8 3.9 3.9 3.9 3.9 3.9 643200 3 .8 3.8 4.0 4.0 4.0 4.0 4.0 643255 4 .0 4.0 4.2 4.2 4.2 4.2 4.2 643157 3 .8 3.8 3.9 3.9 3.9 3.9 3.9 643238 3 .7 3.7 3.8 3.8 3.8 3.8 3.8 643227 4 .0 4.0 4.1 4.1 4.1 4.1 4.1 643164 4 .1 4.1 4.2 4.2 4.2 4.2 4.2 643154 3 .6 3.6 3.7 3.7 3.7 3.7 3.7 643156 4 .1 4.1 4.3 4.3 4.3 4.3 4.3 643208 3 .6 3.6 3.8 3.8 3.8 3.8 3.8 643190 3 .9 3.9 4.0 4.0 4.0 4.0 4.0 518 Company Sanffixed. Does no H-24516: Subchronic Toxicity 90-Day Gavage Study in Rats with One-Generation Reproduction Evaluations Male, V - 643250 643243 643311 643318 643247 643175 643314 643275 643257 643224 643169 643159 643286 643181 643206 643313 643182 643146 643312 643199 643267 643216 643244 643245 643301 643200 643255 643157 643238 643227 643164 643154 643156 643208 643190 Day 63 100 mg/kg/day 3.4 3.9 3.7 4.1 4.0 3.9 3.9 4.1 3.6 3.5 3.4 4.0 3.5 4.1 3.5 3.8 4.3 4 .1 3.7 4.0 4.1 4.5 3.9 3.4 4.1 4.1 4.4 4.2 4.0 4.2 4.4 3.8 4.5 3.9 4.3 Day 64 3.4 3.9 3.7 4.1 4.0 3.9 3.9 4.1 3.6 3 .5 3.4 4.0 3.5 4.1 3.5 3.8 4.3 4.1 3.7 4.0 4.1 4.5 3.9 3.4 4.1 4.1 4.4 4.2 4.0 4.2 4.4 3.8 4.5 3.9 4.3 Day 65 INDIVIDUAL DOSE VOLUMES (mL) Day 66 Day 67 Day 68 3.4 3.4 3.4 3.4 3.9 3.9 3.9 3.9 3.7 3.7 3.7 3.7 4.1 4.1 4.1 4.1 4.0 4.0 4.0 4.0 3.9 3.9 3.9 3.9 3.9 3.9 3.9 3.9 4.1 4.1 4.1 4.1 3.6 3.6 3.6 3.6 3.5 3.5 3.5 3.5 3.4 3.4 3.4 3.4 4.0 4.0 4.0 4.0 3.5 3.5 3.5 3.5 4.1 4.1 4.1 4.1 3.5 3.5 3.5 3.5 3.8 3.8 3.8 3.8 4.3 4 .3 4.3 4.3 4.1 4.1 4.1 4.1 3.7 3.7 3.7 3.7 4.0 4.0 4.0 4.0 4.1 4.1 4.1 4.1 4.5 4.5 4.5 4.5 3.9 3.9 3.9 3.9 3.4 3.4 3.4 3.4 4.1 4.1 4.1 4.1 4.1 4.1 4.1 4.1 4.4 4.4 4.4 4.4 4.2 4.2 4.2 4.2 4.0 4.0 4.0 4.0 4.2 4.2 4.2 4.2 4-4 4.4 4.4 4.4 3.8 3.8 3.8 3.8 4.5 4.5 4.5 4.5 3.9 3.9 3.9 3.9 4.3 4.3 4.3 4.3 Day 69 3.4 3.9 3.7 4.1 4.0 3.9 3.9 4.1 3.6 3.5 3.4 4.0 3.5 4.1 3.5 3.8 4.3 4.1 3.7 4.0 4.1 4.5 3.9 3.4 4.1 4.1 4.4 4.2 4.0 4.2 4.4 3.8 4.5 3.9 4.3 Day 7 3 4 3 4 4 3 4 4 3 3 3 4 3 4 3 3 4 4 3 4 4 4 3 3 4 4 4 4 4 4 4 4 519 Company Sanitized. Doea n H-24516: Subchronic Toxicity 90-Day Gavage Study in Rats with One-Generation Reproduction Evaluations INDIVIDUAL DOSE VOLUMES (mL) Day 72 Day 73 Day 74 Day 75 Day 76 Day 77 Day 78 Day Male, V - 100 ing/kg/day 643250 3 .5 3.5 3.5 3.5 3.5 3.5 3.5 643243 4 .0 4.0 4.0 4.0 4.0 4.1 4.1 643311 3 .8 3.8 3.8 3.8 3.8 3.8 3.8 643318 4 .2 4.2 4.2 4.2 4.2 4.3 4.3 643247 4 .1 4.1 4.1 4.1 4.1 4.2 4.2 643175 3 .4 3.4 3.4 3.4 3.4 AK TEST DAY 77 643314 4 .0 4.0 4.0 4.0 4.0 4.0 4.0 643275 4 .2 4.2 4.2 4.2 4.2 4.2 4.2 643257 3 .7 3.7 3.7 3.7 3.7 3.6 3.8 643224 3 .5 3.5 3.5 3.5 3.5 3.6 3.6 643169 3 .5 3.5 3.5 3.5 3.5 3.6 3.6 643159 4 .0 4.0 4.0 4.0 4.0 4.1 4.1 643286 3 .6 3.6 3.6 3.6 3.6 3.7 3.7 643181 4 .3 4.3 4.3 4.3 4.3 4.4 4.4 643206 3 .6 3.6 3.6 3.6 3.6 3.5 3.5 643313 3 .8 3.8 3.8 643182 4 .4 4.4 4.4 643146 4 .3 4.3 4.3 643312 3 .8 3.8 3.8 643199 4 .1 4.1 4.1 643267 4 .3 4.3 4.3 643216 4 .6 4.6 4.6 643244 3 .9 3.9 3.9 643245 3 .5 3.5 3.5 643301 4 .2 4.2 4.2 643200 4 .2 4.2 4.2 643255 4 .5 4.5 4.5 643157 4 .3 4.3 4.3 64323B 4 .1 4.1 4.1 643227 4 .3 4.3 4.3 643164 4 .5 4.5 4.5 643154 3 .9 3.9 3.9 643156 4 .6 4.6 4.6 643208 4 .0 4.0 4.0 643190 4 .2 4.2 4.2 520 Company SanBbed. Doe* not H-24516: Subchronic Toxicity 90-Day Gavage Study in Rats with One-Generation Reproduction Evaluations INDIVIDUAL DOSE VOLUMES (mL) Day 81 Day 82 Day 83 Day 84 Day 85 Day 86 Day 87 Day Male, V - 100 nig/kg/day 643250 3 .5 3.5 3.5 3.6 3.6 3.6 3.6 643243 4 .1 4.1 4.1 4.1 4.1 4.1 4.1 643311 3 .8 3.8 3.8 3.9 3.9 3.9 3.9 643318 4 .3 4.3 4.3 4.3 4.3 4.3 4.3 643247 4 .2 4.2 4.2 4.2 4.2 4.2 4 .2 643175 643314 4 .0 4.0 4.0 3.6 3.6 3.6 3.6 643275 4 .2 4.2 4.2 4.1 4.1 4.1 4.1 643257 3 .8 3.8 3.8 3.8 3.8 3.8 3.8 643224 3 .6 3.6 3.6 3.7 3.7 3.7 3.7 643169 3 .6 3.6 3.6 3.6 3.6 3.6 3.6 643159 4 .1 4.1 4.1 4.0 4.0 4.0 4.0 643286 3 .7 3.7 3.7 3.8 3.8 3.8 3.8 643181 4.4' 4.4 4.4 4.5 4.5 4.5 4.5 643206 3 .5 3.5 3.5 3.7 3.7 3.7 3.7 643313 643182 643146 643312 643199 643267 643216 643244 643245 643301 643200 643255 643157 643238 643227 643164 643154 643156 643208 643190 521 Company SanRfaed. Does not H-24516: Subchronic Toxicity 90-Day Gavage Study in Rats with One-Generation Reproduction Evaluations Male, V 643250 643243 643311 64331B 643247 643175 643314 643275 643257 643224 643169 643159 643286 643181 643206 643313 643182 643146 643312 643199 643267 643216 643244 643245 643301 643200 643255 643157 643238 643227 643164 643154 643156 643208 643190 Day 90 100 mg/kg/day 3.7 4.2 3.9 4.4 4.3 4.0 4.1 3.9 3.7 INDIVIDUAL DOSE VOLUMES (mL) 522 Company Sanitized. Does H-24516: Subchronic Toxicity 90-Day Gavage Study in Rats with One-Generation Reproduction Evaluations Day 0 Day 1 Male, VII - 643194 643252 643260 643315 643215 643193 643298 643201 643253 643174 643283 643149 643178 643152 643295 643289 643171 643158 643249 643161 643309 64324B 643285 643278 643299 643274 643192 643222 643160 643191 643203 643282 643302 643317 643225 643296 643258 643316 643220 643236 643165 643266 643151 643234 643281 250 nig/kg/day 2.4 2.4 2.2 2.2 2.3 2.3 2.4 2.4 2.7 2.7 2.7 2.7 2.5 2.5 2.7 2.7 2.4 2,4 2.8 2.8 2.4 2.4 2.6 2.6 2.3 2.3 2.9 2.9 2.5 2.5 2.1 2.1 2.6 2.6 2.6 2.6 2.5 2.5 2.6 2.6 2.9 2.9 2.6 - 2.6 2.5 2.5 2.4 2.4 2.4 2.4 2.4 2.4 2.6 2.6 2.6 2.6 2.4 2.4 2.7 2.7 2.5 2.5 2.8 2.8 2.5 2.5 2.5 2.5 2.6 2.6 2.7 2.7 2.3 2.3 2.4 2.4 2.5 2.5 2.5 2.5 2.4 2.4 2.5 2.5 2.3 2.3 2.8 2.8 2.4 2.4 Day 2 2.4 2.2 2.3 2.4 2.7 2.7 2.5 2.7 2.4 2.8 2.4 2.6 2.3 2.9 2.5 2.1 2.6 2.6 2.5 2.6 2.9 2.6 2.5 2.4 2.4 2.4 2.6 2.6 2.4 2.7 2.5 2.8 2.5 2.5 2.6 2.7 2.3 2.4 2.5 2.5 2.4 2.5 2.3 2.8 2.4 Day 3 2.4 2.2 2.3 2.4 2.7 2.7 2.5 2.7 2.4 2.8 2.4 2.6 2.3 2.9 2.5 2.1 2.6 2.6 2.5 2.6 2.9 2.6 2.5 2.4 2.4 2.4 2.6 2.6 2.4 2.7 2.5 2.8 2.5 2.5 2.6 2.7 2.3 2.4 2.5 2.5 2.4 2.5 2.3 2.8 2.4 INDIVI:E)UAL DOEili VOLUMEii (mL) Day 4 Day 5 Day 6 Day 7 2.4 2.4 2.4 3.0 2.2 2.2 2.2 2.9 2.3 2.3 2.3 2.8 2.4 2.4 2.4 2.9 2.7 2.7 2.7 3.3 2.7 2.7 2.7 3.4 2.5 2.5 2.5 3.3 2.7 2.7 2.7 3.3 2.4 2.4 2.4 2.9 2.8 2.8 2.8 3.5 2.4 2.4 2.4 2.9 2.6 2.6 2.6 3.1 2.3 2.3 2.3 2.7 2.9 2.9 2.9 3 .5 2.5 2.5 2-5 3.0 2.1 2.1 2.1 2.7 2.6 2.6 2.6 3.3 2.6 2.6 2.6 3.4 2.5 2.5 2.5 3.1 2.6 2.6 2.6 3.2 2.9 2.9 2.9 3.7 2.6 2.6 2.6 3.1 2.5 2.5 2.5 3.1 2.4 2.4 2.4 2.9 2.4 2.4 2.4 3.0 2.4 2.4 2.4 3.0 2.6 2.6 2.6 3.2 2.6 2.6 2.6 3.2 2.4 2.4 2.4 3.0 2.7 2.7 2.7 3.4 2.5 2.5 2.5 3.2 2.8 2.8 2.8 3.5 2.5 2.5 2.5 3.0 2.5 2.5 2.5 3-0 2.6 2.6 2.6 3.3 2.7 2.7 2.7 3.4 2.3 2.3 2.3 3.0 2.4 2.4 2.4 3.0 2.5 2.5 2.5 3.1 2.5 2.5 2.5 3.1 2.4 2.4 2.4 3.0 2.5 2.5 2.5 3.1 2.3 2.3 2.3 2.8 2.8 2.8 2.8 3.4 2.4 2.4 2.4 3.0 Day 8 3.0 2.9 2.8 2.9 3.3 3.4 3.3 3.3 2.9 3.5 2.9 3.1 2.7 3.5 3.0 2.7 3.3 3.4 3.1 3.2 3.7 3.1 3.1 2.9 3.0 3.0 3.2 3.2 3.0 3.4 3.2 3.5 3.0 3.0 3.3 3.4 3.0 3.0 3.1 3.1 3.0 3.1 2.8 3.4 3.0 Day 9 3.0 2.9 2.8 2.9 3.3 3.4 3.3 3.3 2.9 3.5 2.9 3.1 2.7 3.5 3.0 2.7 3.3 3.4 3.1 3.2 3.7 3.1 3.1 2.9 3.0 3.0 3.2 3.2 3.0 3.4 3.2 3.5 3.0 3.0 3.3 3.4 3.0 3.0 3.1 3.1 3.0 3.1 2.8 3.4 3.0 Day 2 2 2 2 2 3 523 Company SanMzed. Do-- not c H-24516: Subchronic Toxicity 90-Day Gavage Study in Rats with One-Generation Reproduction Evaluations Day 12 Day 13 Male, VII - 643194 643252 643260 643315 643215 643193 643298 643201 643259 643174 643283 643149 643178 643152 643295 643289 643171 643158 643249 643161 643309 643248 643285 643278 643299 643274 643192 643222 643160 643191 643203 643282 643302 643317 643225 643296 643258 643316 643220 643236 643165 643266 643151 643234 643281 250 mg/kg/day 3.0 2.9 2.8 2.9 3.3 3.4 3.3 3.3 2.9 3.5 2.9 3.1 2.7 3.5 3.0 2.7 3.3 3 .4 3.1 3.2 3.7 3.1 3.1 2.9 3.0 3.0 3.2 3.2 3.0 3.4 3.2 3 .5 3.0 3.0 3.3 3.4 3.0 3.0 3.1 3.1 3.0 3.1 2.8 3.4 3.0 3. 0 2. 9 2. 8 2. 9 3 .3 3. 4 3. 3 3. 3 2. 9 3. 5 2. 9 3. 1 2. 7 3. 5 3.,0 2,,7 3,.3 3,.4 3..1 3..2 3 .7 -3..1 3..1 2 .9 3 .0 3 .0 3 .2 3 .2 3 .0 3 .4 3 .2 3 .5 3 .0 3 .0 3 .3 3 .4 3 .0 3 .0 3 .1 3 .1 3 .0 3 .1 2 .8 3 .4 3 .0 Day 14 3.4 3.3 3.2 3.3 3.7 3.8 3.8 3.8 3.4 3.9 3.4 3.6 3.1 4.1 3.4 3.1 3.9 3.9 3.6 3.6 4.2 3.5 3.5 3.4 3.5 3.5 3.7 3.7 3.3 3.8 3.7 4.1 3.5 3.5 3.7 3.9 3.5 3.5 3.6 3.6 3.5 3.7 3.3 3.8 3.4 Day 15 3.4 3.3 3.2 3.3 3.7 3.8 3.8 3.8 3.4 3.9 3.4 3.6 3.1 4.1 3.4 3.1 3.9 3.9 3.6 3.6 4.2 3.5 3.5 3.4 3.5 3.5 3.7 3.7 3.3 3.8 3.7 4.1 3.5 3.5 3.7 3.9 3.5 3.5 3.6 3.6 3.5 3.7 3.3 3.8 3.4 INDIVIDUAL DOSE VOLUMES (mL) Day 16 Day 17 Day 18 Day 19 3.4 3.4 3. 4 3.4 3.3 3.3 3. 3 3.3 3.2 3.2 3. 2 3.2 3.3 3.3 3. 3 3.3 3.7 3.7 3. 7 3.7 3.8 3.8 3. 8 3.8 3.8 3.8 3. 8 3.8 3.8 3.8 3. 8 3.8 3.4 3.4 3. 4 3.4 3.9 3.9 3. 9 3.9 3.4 3.4 3. 4 3.4 3.6 3.6 3. 6 3.6 3.1 3.1 3. 1 3.1 4.1 4.1 4. 1 4.1 3.4 3.4 3..4 3.4 3.1 3.1 3..1 3.1 3.9 3.9 3..9 3.9 3.9 3.9 3 ..9 3.9 3.6 3.6 3,.6 3.6 3.6 3.6 3,.6 3.6 4.2 4.2 4 .2 4.2 3.5 3.5 3,.5 3.5 3.5 3.5 3 .5 3.5 3.4 3.4 3 .4 3.4 3.5 3.5 3 .5 3.5 3.5 3.5 3 .5 3.5 3.7 3.7 3 .7 3.7 3.7 3.7 3 .7 3.7 3.3 3.3 3 .3 3.3 3.8 3.8 3 .8 3.8 3.7 3.7 3 .7 3.7 4.1 4.1 4 .1 4.1 3.5 3.5 3 .5 3.5 3.5 3.5 3 .5 3.5 3.7 3.7 3 .7 3.7 3.9 3.9 3 .9 3.9 3.5 3.5 3 .5 3.5 3.5 3.5 3 .5 3.5 3.6 3.6 3 .6 3.6 3.6 3.6 3 .6 3.6 3.5 3.5 3 .5 3.5 3.7 3.7 3 .7 3.7 3.3 3.3 3 .3 3.3 3.8 3.8 3 .8 3.8 3.4 3.4 3 .4 3.4 Day 20 3.4 3.3 3.2 3.3 3.7 3.8 3.8 3.8 3.4 3.9 3.4 3.6 3.1 4.1 3.4 3.1 3.9 3.9 3.6 3.6 4.2 3.5 3.5 3.4 3.5 3.5 3.7 3.7 3.3 3.8 3.7 4.1 3.5 3.5 3.7 3.9 3.5 3.5 3.6 3.6 3.5 3.7 3.3 3.8 3.4 Day 21 3.8 3.7 3.5 3.7 4.2 4.3 4.2 4.3 3.9 4.5 3.7 4.0 3.4 4.6 3.8 3.5 4.5 4 .4 3.9 4.2 4.7 3.9 3.9 3.8 3.9 3.9 4.2 4.1 3.8 4.2 4.2 4.7 3.9 3.9 4.1 4.4 4.0 4.0 4.0 4.1 4.0 4.1 3.6 4.3 3.9 Day 2 3 3 3 3 4 4 4 4 3 4 3 4 3 4 3 3 4 4 3 4 4 3 3 3 3 3 4 4 3 4 4 4 3 3 4 4 4 4 4 4 4 4 3 4 3 524 Company Sanitized. Does not c \_y H-24516: Subchronic Toxicity 90-Day Gavage Study in Rats with One-Generation Reproduction Evaluations Day 24 Day 25 Male, VII - 250 mg/kg/day 643194 643252 643260 643315 643215 643133 643298 643201 643259 643174 643283 643149 643178 643152 643295 643289 643171 643158 643249 643161 643309 643248 643285 643278 643299 643274 643192 643222 643160 643191 643203 643282 643302 643317 643225 643296 643258 643316 643220 643236 643165 643266 643151 643234 643281 3.8 3.8 3.7 3.7 3.5 3.5 3.7 3.7 4.2 4.2 4.3 4.3 4.2 4.2 4.3 4.3 3.9 3.9 4.5 4.5 3.7 3.7 4.0 4.0 3.4 3.4 4.6 4.6 3.8 3.8 3.5 3.5 4.5 4.5 4.4 4.4 3.9 3.9 4.2 4.2 4.7 4.7 3.9 .3.9 3.9 3.9 3.8 3.8 3.9 3.9 3.9 3.9 4.2 4.2 4.1 4.1 3.8 3.8 4.2 4.2 4.2 4 .2 4.7 4.7 3.9 3.9 3.9 3.9 4.1 4.1 4.4 4.4 4.0 4.0 4.0 4.0 4.0 4.0 4.1 4.1 4.0 4.0 4.1 4.1 3.6 3.6 4.3 4.3 3.9 3.9 Day 26 3.8 3.7 3.5 3.7 4.2 4.3 4.2 4.3 3.9 4.5 3.7 4.0 3.4 4.6 3.8 3.5 4.5 4.4 3.9 4.2 4.7 3.9 3.9 3.8 3.9 3.9 4.2 4.1 3.8 4.2 4.2 4.7 3.9 3.9 4.1 4.4 4.0 4.0 4.0 4.1 4.0 4.1 3.6 4.3 3.9 Day 27 3.8 3.7 3.5 3.7 4.2 4.3 4.2 4.3 3.9 4.5 3.7 4.0 3.4 4.6 3.8 3.5 4.5 4 .4 3.9 4 .2 4.7 3.9 3.9 3.8 3.9 3.9 4.2 4.1 3.8 4.2 4 .2 4.7 3.9 3.9 4.1 4.4 4.0 4.0 4.0 4.1 4.0 4.1 3.6 4.3 3.9 INDIVI:r)UAL D0!Ei VOLUME;i (mL) Day 28 Day 29 Day 30 Day 31 4.1 4.1 4.1 4.1 4.0 4.0 4.0 4.0 3.8 3.8 3.8 3.8 4.0 4.0 4.0 4.0 4.5 4.5 4.5 4.5 4.6 4.6 4.6 4.6 4.5 4.5 4.5 4.5 4.6 4.6 4.6 4.6 4.3 4.3 4.3 4.3 4.9 4.9 4.9 4.9 4.0 4.0 4.0 4.0 4.4 4.4 4.4 4.4 2.9 2.9 2.9 2.9 5.0 3.0 5.0 5.0 4.1 4.1 4.1 4.1 3.8 3.8 3.8 3.8 4.8 4.8 4.8 4.8 4.6 4.6 4.6 4.6 4.2 4.2 4.2 4.2 4.5 4.5 4.5 4.5 5.0 5.0 5.0 5.0 4.2 4.2 4.2 4.2 4.2 4.2 4.2 4.2 4.1 4.1 4.1 4.1 4.2 4.2 4.2 4.2 4.2 4.2 4.2 4.2 4.6 4.6 4.6 4.6 4.4 4.4 4.4 4.4 4.0 4.0 4.0 4.0 4.4 4.4 4.4 4.4 4.5 4.5 4.5 4.5 5.1 5.1 5.1 5.1 4.2 4.2 4.2 4.2 4.2 4.2 4.2 4.2 4.3 4.3 4.3 4.3 4.7 4.7 4.7 4.7 4.3 4.3 4.3 4.3 4.3 4.3 4.3 4.3 4 .3 4.3 4.3 4.3 4.5 4.5 4.5 4.5 4.3 4.3 4.3 4.3 4.S 4.5 4.5 4.5 4.0 4.0 4.0 4.0 4.6 4.6 4.6 4.6 4.2 4.2 4.2 4.2 Day 32 4.1 4.0 3.8 4.0 4.5 4.6 4.5 4.6 4.3 4.9 4.0 4.4 2.9 5.0 4.1 3.8 4.8 4.6 4.2 4.5 5.0 4.2 4.2 4.1 4.2 4.2 4.6 4.4 4.0 4.4 4.5 5.1 4.2 4.2 4.3 4.7 4.3 4.3 4.3 4.5 4.3 4.5 4.0 4.6 4.2 Day 33 4.1 4.0 3.8 4.0 4.5 4.6 4.5 4.6 4.3 4 .9 4.0 4.4 2.9 5.0 4.1 3.8 4.8 4.6 4.2 4.5 5.0 4.2 4.2 4.1 4.2 4.2 4.6 4.4 4.0 4.4 4.5 5.1 4.2 4.2 4.3 4.7 4.3 4.3 4.3 4.5 4.3 4.5 4.0 4.6 4.2 Day 3 4 4 3 4 4 4 4 4 4 4 4 4 2 5 4 3 4 4 4 4 5 4 4 4 4 4 4 4 4 4 4 5 4 4 4 4 4 4 4 4 4 4 4 4 4 525 Company SanWzed. Does not con H-24516: Subchronic Toxicity 90-Day Gavage Study in Rats with One-Generation Reproduction Evaluations Day 36 Day 37 Male, VII - 250 nig/kg/day 643194 643252 643260 643315 643215 643193 643298 643201 643259 643174 643283 643149 643178 643152 643295 643289 643171 643158 643249 643161 643309 643248 643285 643278 643299 643274 643192 643222 643160 643191 643203 643282 643302 643317 643225 643296 643258 643316 643220 643236 643165 643266 643151 643234 643281 4 .3 4 .3 4 .0 4 .3 4 .7 4 .8 4 .8 4 .9 4 .5 5 .2 4 .2 4 .7 3 .2 5 .3 4 .3 4 .0 5 .1 4 .9 4 .6 4 .9 5 .3 4.4 4 .4 4 .3 4 .4 4 .5 4 .9 4 .7 4 .2 4 .6 4 .8 5 .4 4 .5 4 .5 4 .5 5 .0 4 .6 4 .6 4 .5 4 .5 4 .6 4 .8 4 .2 4.9 4 .5 4 .3 4 .3 4 .0 4 .3 4 .7 4 .8 4 .8 4 .9 4 .5 5 .2 4 .2 4 .7 3 .2 5 .3 4 .3 4 .0 5 .1 4 .9 4 .6 4 .9 5 .3 .4 .4 4 .4 4 .3 4 .4 4 .5 4 .9 4 .7 4 .2 4 .6 4 .8 5 .4 4 .5 4 .5 4 .5 5 .0 4 .6 4 .6 4 .5 4 .5 4 .6 4 .8 4 .2 4 .9 4 .5 Day 38 3 .2 3 .3 3 .0 3 .2 3 .5 3 .6 3 .6 3 .7 3 .4 3 .9 3 .1 3 .5 2 .4 4 .0 3 .2 3 .0 3 .8 3 .7 3 .5 3 .6 4 .0 3 .3 3 .3 3 .2 3 .3 3 .4 3 .7 3 .5 3 .2 3 .5 3 .6 4 .0 3 .3 3 .3 3 .4 3 .7 3 .4 3 .4 3 .4 3 .4 3 .5 3 .6 3 .1 3 .7 3 .4 INDIVIDUAL DOSE VOLUMES (mL) Day 39 Day 40 Day 41 Day 42 3.2 3.2 3.2 3.4 3.3 3.3 3.3 3.4 3.0 3.0 3.0 3.1 3.2 3.2 3.2 3.4 3.5 3.5 3.5 3.6 3.6 3.6 3.6 3.8 3.6 3.6 3.6 3.7 3.7 3.7 3.7 3.9 3.4 3.4 3.4 3.6 3.9 3.9 3.9 4.0 3.1 3.1 3.1 3.2 3.5 3.5 3.5 3.7 2.4 2.4 2.4 2.7 4.0 4.0 4.0 4.1 3.2 3.2 3.2 3.4 3.0 3.0 3.0 3.2 3.8 3.8 3.8 4.0 3.7 3.7 3.7 3.8 3.5 3.5 3.5 3 .7 3.6 3.6 3.6 3.7 4.0 4.0 4.0 4.1 3.3 3.3 3.3 3.5 3.3 3.3 3.3 3.4 3.2 3.2 3.2 3.4 3.3 3.3 3.3 3.5 3.4 3.4 3.4 3.5 3.7 3.7 3.7 3.9 3.5 3.5 3.5 3.7 3.2 3.2 3.2 3.3 3.5 3.5 3.5 3.6 3.6 3.6 3.6 3.7 4.0 4.0 4.0 4.2 3.3 3.3 3.3 3.5 3.3 3.3 3.3 3.5 3.4 3.4 3.4 3.6 3.7 3.7 3.7 3.8 3.4 3.4 3.4 2.9 3.4 3.4 3.4 3.5 3.4 3.4 3.4 3.5 3.4 3.4 3.4 3.5 3.5 3.5 3.5 3.6 3.6 3.6 3.6 3.8 3.1 3.1 3.1 3.2 3.7 3.7 3.7 3.8 3.4 3.4 3.4 3.4 Day 43 3.4 3.4 3.1 3.4 3.6 3.8 3.7 3.9 3.6 4.0 3.2 3.7 2.7 4.1 3.4 3.2 4.0 3.8 3.7 3.7 4.1 3.5 3.4 3.4 3.5 3.5 3.9 3.7 3.3 3.6 3.7 4.2 3.5 3.5 3.6 3.8 2.9 3.5 3.5 3.5 3.6 3.8 3.2 3.8 3.4 526 Company Sanitized. Does n H-24516: Subchronic Toxicity 90-Day Gavage Study in Rats with One-Generation Reproduction Evaluations Day 45 Day 46 Male, VII - 250 mg/kg/day 643194 3.4 3.4 643252 3.4 3.4 643260 3.1 3.1 643315 3.4 3.4 643215 3.6 3.6 643193 3.8 3.8 643298 3.7 3.7 643201 3.9 3.9 643259 3.6 3.6 643174 4.0 4.0 6432B3 3.2 3.2 643149 3.7 3.7 643178 2.7 2.7 643152 4.1 4.1 643295 3.4 3.4 643289 3.2 3.2 643171 4.0 4.0 643158 3.8 3.8 643249 3.7 3.7 643161 3.7 3.7 643309 4.1 4.1 643248 3.5 3.5 643285 3.4 3.4 643278 3.4 3.4 643299 3.5 3.5 643274 3.5 3.5 643192 3.9 3.9 643222 3.7 3.7 643160 3.3 3.3 643191 3.6 3.6 643203 3.7 3.7 6432B2 4.2 4.2 643302 3.5 3.5 643317 3.5 3.5 643225 3.6 3.6 643296 3.8 3.8 643258 2.9 2.9 643316 3.5 3.5 643220 3.5 3.5 643236 3.5 3-5 643165 3.6 3.6 643266 3.8 3.8 643151 3.2 3.2 643234 3.8 3.8 643281 3.4 3.4 Day 47 INDIVIDUAL DOSE VOLUMES (mL) Day 48 Day 49 Day 50 3.4 3.4 3.5 3.5 3.4 3.4 3.3 3.3 3.1 3.1 3.1 3.1 3-4 3.4 3.4 3.4 3.6 3.6 3.6 3.6 3.8 3.8 3.8 3.8 3.7 3.7 3.7 3.7 3.9 3.9 3.8 3.8 3.6 3.6 3.5 3.5 4.0 4.0 4.0 4.0 3.2 3.2 3.2 3.2 3.7 3.7 3.8 3.8 2.7 2.7 2.7 2.7 4.1 4.1 4.3 4.3 3.4 3.4 3.4 3.4 3.2 3.2 3.2 3.2 4.0 4.0 4.1 4.1 3 .8 3.8 4.0 4.0 3.7 3.7 3.7 3.7 3.7 3.7 3.8 3.8 4.1 4.1 4.2 4.2 3.5 3.5 3.4 3.4 3.4 3.4 3.5 3.5 3.4 3.4 3.4 3.4 3.5 3.5 3.6 3.6 3.5 3 .5 3.6 3.6 3.9 3.9 3.9 3.9 3.7 3.7 3.7 3.7 3.3 3.3 3.4 3.4 3.6 3.6 3.7 3.7 3.7 3.7 3.8 3.8 4.2 4.2 4.4 4.4 3.5 3.5 3.6 3.6 3.5 3.5 3.5 3.5 3.6 3.6 3.6 3.6 3.8 3.8 3.9 3.9 2.9 2.9 3.3 3.3 3.5 3.5 3.6 3.6 3.5 3.5 3.5 3.5 3.5 3.5 3.6 3.6 3.6 3.6 3.4 3.4 3.8 3.8 3.9 3.9 3.2 3.2 3.3 3.3 3.8 3.8 3.9 3.9 3.4 3.4 3.6 3.6 Day 51 3.5 3.3 3.1 3.4 3.6 3.8 3.7 3.8 3.5 4.0 3 .2 3.8 2.7 4.3 3.4 3.2 4.1 4 .0 3.7 3.8 4.2 3.4 3.5 3.4 3.6 3.6 3.9 3.7 3.4 3.7 3.8 4.4 3.6 3.5 3.6 3.9 3.3 3.6 3.5 3.6 3.4 3.9 3.3 3.9 3.6 Day 5 3 3 3 3 3 3 3 3 3 4 3 3 2 4 3 3 4 4 3 3 4 3 3 3 3 3 3 3 3 3 3 4 3 3 3 3 3 3 3 3 3 3 527 Company SanRbed. Does not con H-24516: Subchronic Toxicity 90-Day Gavage Study in Rats with One-Generation Reproduction Evaluations INDIVIDUAL DOSE VOLUMES (mL) Day 54 Day SS Day 56 Day 57 Day 58 Day 59 Day 60 Day Male, VII - 250 ing/kg/day 643194 3.5 3.5 3.6 3.6 3.6 3.6 3.6 643252 3.3 3.3 3.4 3.4 3.4 3.4 3.4 643260 3.1 3.1 3.2 3.2 3.2 3.2 3.2 643315 3.4 3.4 3.4 3.4 3.4 3.4 3.4 643215 3.6 3.6 3.7 3.7 b 3.7 3.7 3.7 643193 3.8 3.8 3.1 3.1 3.1 3.1 3.1 643298 3.7 3.7 3.9 3.9 3.9 3.9 3.9 643201 3.8 3.8 3.8 3.8 3.8 3.8 3.8 643259 3.5 3.5 3.5 3.5 3.5 3.5 3.5 643174 4.0 4.0 4.1 4 .1 4.1 4.1 4.1 643283 3.2 3.2 3.2 3.2 3.2 3.2 3.2 643149 3.8 3.8 3.9 3.9 3.9 3.9 3.9 643178 2.7 2.7 2.8 2.8 2.8 2.8 2 .8 643152 4.3 4.3 4.3 4.3 4.3 4.3 4.3 643295 3.4 3.4 2.9 2.9 2.9 2.9 2.9 643289 3.2 3.2 2.9 2.9 2.9 2.9 2.9 643171 4.1 4.1 4.1 4.1 4.1 4.1 4.1 643158 4.0 4.0 4.1 4.1 4 .1 4.1 4.1 643249 3.7 3.7 3.8 3.8 3.8 3.8 3.8 643161 3.8 3.8 3.9 3.9 3.9 3.9 3.9 643309 4.2 4.2 3.7 3.7 3.7 3.7 3.7 643248 3.4 3.4 3.5 3.5 3.5 3.5 3.5 643285 3.5 3.5 3.5 3.5 3.5 3.5 3.5 643278 3.4 3.4 3.6 3.6 3.6 3.6 3.6 643299 3.6 3.6 3.7 3.7 3.7 3.7 3-7 643274 3.6 3.6 3.7 3.7 3.7 3.7 3.7 643192 3.9 3.9 4.0 4.0 4.0 4.0 4.0 643222 3.7 3.7 3.8 3.8 3.8 3.8 3.8 643160 3.4 3.4 3.5 3.5 3.5 3.5 3.5 643191 3.7 3.7 3.7 3.7 3.7 3.7 3.7 643203 3.8 3.8 3.8 3.8 3.8 3.8 3.8 643282 4.4 4.4 4.4 4.4 4.4 4.4 4.4 643302 3.6 3.6 3.6 3.6 3.6 3.6 3.6 643317 3.5 3.5 3.6 3.6 3.6 3.6 3.6 643225 3.6 3.6 3.6 3.6 3.6 3.6 3.6 643296 3.9 3.9 4.0 4.0 4.0 4.0 4.0 643258 3.3 3.3 3.4 3.4 3.4 3.4 3.4 643316 3.6 3.6 3.7 3.7 3.7 3.7 3.7 643220 3.5 3.5 3.5 3.5 3.5 3.5 3.5 643236 3.6 3.6 3.8 3.8 3.8 3.8 3.8 643165 3.4 3.4 3.4 3.4 3.4 3.4 3.4 643266 3.9 3.9 3.9 3.9 3.9 3.9 3.9 643151 3.3 3.3 3.4 3.4 3.4 3.4 3.4 643234 3.9 3.9 3.9 3.9 3.9 3.9 3.9 643281 3.6 3.6 3.7 3.7 3.7 3.7 528 Company Sanffized. Does no H-24516: Subchronic Toxicity 90-Day Gavage Study in Rats with One-Generation Reproduction Evaluations Day 63 Day 64 Male, VII - 250 mg/kg/day 643194 3.7 3.7 643252 3.6 3.6 643260 3.3 3.3 643315 3.6 3.6 643215 3.7 3.7 643193 3.5 3.5 643298 4.0 4.0 643201 4.0 4.0 643259 3.5 3.5 643174 4.3 4.3 643283 3.2 3.2 643149 3.9 3.9 643178 2.8 2.8 643152 4.4 4.4 643295 2.9 2.9 643289 3.0 3.0 643171 4.1 4.1 643158 4.2 4.2 643249 3.9 3.9 643161 3.6 3.6 643309 4.0 4.0 643248 3.2 3.2 643285 3.4 3.4 643278 3.3 3.3 643299 3.7 3.7 643274 3.8 3.8 643192 3.8 3.8 643222 3.7 3.7 643160 3.6 3.6 643191 3.8 3.8 643203 3.9 3 .9 643282 4.3 4.3 643302 3 .4 3.4 643317 3.6 3.6 643225 3.7 3.7 643296 4.0 4.0 643258 3.6 3.6 643316 3.8 3.8 643220 3.3 3.3 643236 3.6 3.6 643165 3.3 3.3 643266 4.0 4.0 643151 3.2 3.2 643234 3.7 3.7 643281 3.8 3.8 Day 65 INDIVIDUAL DOSE VOLUMES Day 66 Day 67 (mL) Day 68 3.7 3.7 3.7 3.7 3.6 3.6 3.6 3.6 3.3 3.3 3.3 3.3 3.6 3.6 3.6 3.6 3.7 3.7 3.7 3.7 3.5 3.5 3.5 3.5 4.0 4.0 4.0 4.0 4.0 4.0 4.0 4.0 3.5 3.5 3.5 3.5 4.3 4.3 4.3 4.3 3.2 3.2 3.2 3.2 3.9 3.9 3.9 3.9 2.8 2.B 2.8 2.8 4.4 4.4 4.4 4.4 2.9 2.9 2.9 2.9 3.0 3.0 3.0 3.0 4.1 4.1 4.1 4.1 4.2 4.2 4.2 4.2 3.9 3.9 3.9 3.9 3.6 3.6 3.6 3.6 4.0 4.0 4.0 4.0 3.2 3.2 3.2 3.2 3.4 3.4 3.4 3.4 3.3 3.3 3.3 3.3 3.7 3.7 3.7 3.7 3.8 3.8 3.8 3.8 3.8 3.8 3.8 3.8 3.7 3.7 3.7 3.7 3.6 3.6 3.6 3.6 3.8 3.8 3.8 3.8 3.9 3.9 3.9 3.9 4.3 4.3 4.3 4.3 3.4 3.4 3.4 3.4 3.6 3.6 3.6 3.6 3.7 3.7 3.7 3.7 4.0 4.0 4.0 4.0 3.6 3.6 3.6 3.6 3.8 3.8 3.8 3.8 3.3 3.3 3.3 3.3 3.6 3.6 3.6 3.6 3.3 3.3 3.3 3.3 4.0 4.0 4.0 4.0 3.2 3.2 3.2 3.2 3.7 3.7 3.7 3.7 3.8 3.8 3.8 3.8 Day 69 3.7 3.6 3.3 3.6 3.7 3.5 4.0 4.0 3.5 4.3 3.2 3.9 2.8 4.4 2.9 3.0 4.1 4.2 3.9 3.6 4.0 3.2 3.4 3.3 3.7 3.8 3.8 3.7 3.6 3.8 3.9 4.3 3.4 3.6 3.7 4.0 3.6 3.8 3.3 3.6 3.3 4.0 3.2 3.7 3.8 Day 7 3 2 3 3 3 3 4 4 3 4 3 3 2 4 2 3 3 4 3 3 3 3 3 529 CompanySanMzad. Dm H-24516: Subchronic Toxicity 90-Day Gavage Study in Rats with One-Generation Reproduction Evaluations INDIVIDUAL DOSE VOLUMES (mL) Day 72 Day 73 Day 74 Day 75 Day 76 Day 77 Day 78 Day Male, VII - 250 ing/kg/day 643194 3 .8 3.8 3.8 3.8 3.8 3.8 3.8 643252 2 .8 2.8 2.8 2.8 2.8 3.4 3.4 643260 3 .3 3.3 3-3 3.3 3.3 3.4 3.4 643315 3 .7 3.7 3.7 3.7 3.7 3.5 3.5 643215 3 .2 3.2 3.2 3.2 3.2 3.7 3.7 643193 3 .6 3.6 3.6 3.6 3.6 3.8 3.8 643298 4 .0 4.0 4.0 4.0 4.0 3.7 3.7 643201 4 .0 4-0 4.0 4.0 4.0 4.1 4.1 643259 3 .7 3.7 3.7 3.7 3.7 3.4 3.4 643174 4 .3 4.3 4.3 4.3 4.3 4.4 4.4 643283 3 .0 3.0 3.0 3.0 3.0 3.3 3.3 643149 3 .9 3.9 3.9 3.9 3.9 4.0 4.0 643178 2 .8 2.8 2.8 2.8 2.8 2.6 2.6 643152 4 .5 4.5 4-5 4 .5 4.5 4.5 4.5 643295 2 .5 2.5 2.5 2.5 2.5 3.2 3.2 643289 3 .2 3.2 3.2 643171 3 .4 3.4 3.4 643158 4 .3 4.3 4.3 643249 3 .4 3.4 3.4 643161 3 .6 3.6 3.6 643309 643248 3 .0 3.0 3.0 643285 3 .3 3.3 3.3 643278 3 .6 3.6 3.6 643299 3 .6 3.6 3.6 643274 3 .8 3.8 3.8 643192 3 .9 3.9 3.9 643222 3 .9 3.9 3.9 643160 3 .6 3.6 3.6 643191 3 .8 3.8 3.8 643203 4 .0 4.0 4.0 643282 3 .7 3.7 3.7 643302 2 .8 2.8 2.8 643317 2 .9 2.9 2.9 643225 3 .8 3.8 3.8 3.8 3.8 3.8 3.8 643296 3 .2 3.2 3.2 3.2 3.2 3.9 3.9 643258 3 .6 3.6 3.6 3.6 3.6 3.1 3.1 643316 3 .8 3.8 3.8 3.8 3.8 3.8 3.8 643220 3 .3 3.3 3.3 3.3 3.3 3.4 3.4 643236 3 .8 3.8 3.8 3.8 3.8 3.6 3.6 643165 3 .5 3.5 3.5 3 .5 3.5 2.9 2.9 643266 4 .0 4.0 4.0 4.0 4.0 3.9 3.9 643151 3 .2 3.2 3.2 3.2 3.2 3.0 3.0 643234 3 .3 3.3 3.3 3.3 3.3 3.8 3.8 643281 3 .8 3.8 3.8 530 Company Sanitized. Doe n H-24516: Subchronic Toxicity 90-Day Gavage Study in Rats with One-Generation Reproduction Evaluations Day 81 Day 82 Male, VII - 250 mg/kg/day 643194 3.8 3.8 643252 3.4 3.4 643260 3.4 3.4 643315 3.5 3.5 643215 3.7 3.7 643193 3.8 3.8 643298 3.7 3.7 643201 4.1 4.1 643259 3.4 3.4 643174 4.4 4.4 643283 3.3 3.3 643149 4.0 4.0 643178 2.6 2.6 643152 4.5 4.5 643295 3.2 3.2 643289 643171 643158 643249 643161 643309 643248 643285 643278 643299 643274 643192 643222 643160 643191 643203 643282 643302 643317 643225 3.8 3.8 643296 3.9 3.9 643258 3.1 3.1 643316 3.8 3.8 643220 3.4 3.4 643236 3.6 3.6 643165 2.9 2.9 643266 3.9 3.9 643151 3.0 3.0 643234 3.8 3.8 643281 Day 83 INDIVIDUAI^ D(3SE VOLUME,S Day 84 Day 85 (mL) Day 86 3.8 3.9 3.9 3.9 3.4 3.8 3.8 3.8 3.4 3.4 3.4 3.4 3.5 3.7 3.7 3.7 3.7 3.9 3.9 3.9 3.8 4.0 4.0 4.0 3.7 4.0 4.0 4.0 4.1 4.2 4.2 4.2 3.4 3.7 3.7 3.7 4.4 4.4 4.4 4.4 3.3 3.3 3.3 3.3 4.0 4.1 4.1 4.1 2.6 2.9 2.9 2.9 4 .5 4.7 4.7 4.7 3.2 3.2 3.2 3.2 3.8 4.0 4.0 4.0 3.9 4.2 4.2 4.2 3.1 3.6 3.6 3.6 3.8 3.9 3.9 3.9 3.4 3.5 3.5 3.5 3.6 3.9 3.9 3.9 2.9 3.6 3.6 3.6 3.9 4.1 4.1 4.1 3.0 3.4 3.4 3.4 3.8 3.8 3.8 3.8 Day 87 3.9 3.8 3.4 3.7 3.9 4.0 4.0 4.2 3.7 4.4 3.3 4.1 2.9 4.7 3.2 4.0 4.2 3.6 3.9 3.5 3.9 3.6 4.1 3.4 3.8 Day 88 3. 3. 3. 3. 3. 4. 4. 4. 3. 4. 3. 4. 2. 4. 3. 4 4 3 3 3 3 3 4 3 3 531 QM9any SmHzod. DOM not c H-24516: Subchronic Toxicity 90-Day Gavage Study in Rats with One-Generation Reproduction Evaluations Day 90 Male, VII - 250 mg/kg/day 643194 4.0 643252 4.0 643260 3.5 643315 3.8 643215 4.0 643193 4.2 643298 4.1 643201 4.3 643259 3.8 643174 4.5 643283 643149 643178 643152 643295 643289 643171 643158 643249 643161 643309 643248 643285 643278 643299 643274 643192 643222 643160 643191 643203 643282 643302 643317 643225 643296 643258 643316 643220 643236 643165 643266 643151 643234 643281 INDIVIDUAL DOSE VOLUMES (mL) 532 Company Sanitized. Does no H-24516: Subchronic Toxicity 90-Day Gavage Study in Rats with One-Generation Reproduction Evaluations Day 0 Day 1 Female, 643477 643374 643406 643486 643361 643463 643398 643436 643362 643354 643402 6433B3 643465 643484 643384 643352 643343 643459 643394 643480 643319 643350 643363 643397 643421 643420 643419 643414 643401 643455 643378 643393 643447 643478 643386 643405 643425 643448 643426 643415 643453 643330 643336 643387 643377 II-O ing/kg/day 1.7 1.7 1.8 1.8 1.6 1.6 1.8 1.8 1.9 1.9 2.2 2.2 1.7 1.7 1.8 1.8 1.8 1.8 1.6 1.6 1.8 1.8 1.7 1.7 2.1 2.1 1.8 1.8 1.9 1.9 1.9 1.9 1.7 1.7 2.1 2.1 1.9 1.9 2.0 2.0 2.0 2.0 1.9 1.9 2.0 "2.0 1.9 1.9 1.8 1.8 2.1 2.1 2.1 2.1 2.1 2.1 1.8 1.8 1.9 1.9 2.2 2.2 1.9 1.9 1.9 1.9 1.8 1.8 1.8 1.8 2.1 2.1 2.0 2.0 2.1 2.1 1.8 1.8 2.1 2.1 2.0 2.0 1.7 1.7 2.0 2.0 1.9 1.9 2.0 2.0 Day 2 1.7 1.8 1.6 1.8 1.9 2.2 1.7 1.8 1.8 1.6 1.8 1.7 2.1 1.8 1.9 1.9 1.7 2.1 1.9 2.0 2.0 1.9 2.0 1.9 1.8 2.1 2.1 2.1 1.8 1.9 2.2 1.9 1.9 1.8 1.8 2.1 2.0 2.1 1.8 2.1 2.0 1.7 2.0 1.9 2.0 Day 3 1.7 1.8 1.6 1.8 1.9 2.2 1.7 1.8 1.8 1.6 1.8 1.7 2.1 1.8 1.9 1.9 1.7 2.1 1.9 2.0 2.0 1.9 2.0 1.9 1.8 2.1 2.1 2.1 1.8 1.9 2.2 1.9 1.9 1.8 1.8 2.1 2.0 2.1 1.8 2.1 2.0 1.7 2.0 1.9 2.0 INDIV]:r)UAL D0il3 VOLUMIii (mL) Day 4 Day 5 Day 6 Day 7 1.7 1.7 1.7 2.0 1.8 1.8 1.8 2.1 1.6 1.6 1.6 1.9 1.8 1.8 1.8 1.9 1.9 1.9 1.9 2.1 2.2 2.2 2.2 2.4 1.7 1.7 1.7 1.9 1.8 1.8 1.8 2.0 1.8 1.8 1.8 2.1 1.6 1.6 1.6 1.7 1.8 1.8 1.8 1.9 1.7 1.7 1.7 1.9 2.1 2.1 2.1 2.2 1.8 1.8 1.8 1.9 1.9 1.9 1.9 2.2 1.9 1.9 1.9 2.1 1.7 1.7 1.7 1.9 2.1 2.1 2.1 2.3 1.9 1.9 1.9 2.3 2.0 2.0 2.0 2.3 2.0 2.0 2.0 2.3 1.9 1.9 1.9 2.1 2.0 2.0 2.0 2.3 1.9 1.9 1.9 2.3 1.8 1.8 1.8 2.0 2.1 2.1 2.1 2.3 2.1 2.1 2.1 2.4 2.1 2.1 2.1 2.5 1.8 1.8 1.8 1.8 1.9 1.9 1.9 2.1 2.2 2.2 2.2 2.4 1.9 1.9 1.9 2.3 1.9 1.9 1.9 2.2 1.8 1.8 1.8 2.0 1.8 1.8 1.8 2.2 2.1 2.1 2.1 2.4 2.0 2.0 2.0 2.3 2.1 2.1 2.1 2.3 1.8 1.8 1.8 2.1 2.1 2.1 2.1 2.4 2.0 2.0 2.0 2.2 1.7 1.7 1.7 1.9 2.0 2.0 2.0 2.2 1.9 1.9 1.9 2.1 2.0 2.0 2.0 2.2 Day 8 2.0 2.1 1.9 1.9 2.1 2.4 1.9 2.0 2.1 1.7 1.9 1.9 2.2 1.9 2.2 2.1 1.9 2.3 2.3 2.3 2.3 2.1 2.3 2.3 2.0 2.3 2.4 2.5 1.8 2.1 2.4 2.3 2.2 2.0 2.2 2.4 2.3 2.3 2.1 2.4 2.2 1.9 2.2 2.1 2.2 Day 9 2.0 2.1 1.9 1.9 2.1 2.4 1.9 2.0 2.1 1.7 1.9 1.9 2.2 1.9 2.2 2.1 1.9 2.3 2.3 2.3 2.3 2.1 2.3 2.3 2.0 2.3 2.4 2.5 1.8 2.1 2.4 2.3 2.2 2.0 2.2 2.4 2.3 2.3 2.1 2.4 2.2 1.9 2.2 2.1 2.2 Day 1 2 2 1 1 2 2 1 2 2 1 1 1 2 1 2 2 1 2 2 2 2 2 2 2 2 2 2 2 1 2 2 2 2 2 2 2 2 2 2 2 2 1 2 2 2 533 Company SanMzed. Does not H-24516: Subchronic Toxicity 90-Day Gavage Study in Rats with One-Generation Reproduction Evaluations Day 12 Day 13 Female, II - 0 mg/kg/day 643477 643374 643406 643486 643361 643463 643398 643436 643362 643354 643402 643383 643465 643484 643384 643352 643343 643459 643394 643480 643319 643350 643363 643397 643421 643420 643419 643414 643401 643455 643378 643393 643447 643478 643386 643405 643425 643448 643426 643415 643453 643330 643336 643387 643377 2. 0 2. 1 1. 9 1. 9 2. 1 2.4 1. 9 2. 0 2. 1 1. 7 1. 9 1. 9 2. 2 1. 9 2. 2 2. 1 1. 9 2. 3 2. 3 2. 3 2. 3 2. 1 2. 3 2. 3 2. 0 2. 3 2. 4 2. 5 1. 8 2. 1 2. 4 2. 3 2. 2 2. 0 2. 2 2. 4 2. 3 2. 3 2. 1 2.4 2. 2 1.,9 2.,2 2..1 2. 2 2 .0 2 .1 1 .9 1 .9 2 .1 2.4 1 .9 2 .0 2 .1 1 .7 1 .9 1 .9 2 .2 1 .9 2 .2 2 .1 1 .9 2 .3 2 .3 2 .3 2 .3 .2.1 2.3 2 .3 2 .0 2 .3 2 .4 2 .5 1 .8 2 .1 2 .4 2 .3 2 .2 2 .0 2 .2 2 .4 2 .3 2 .3 2 .1 2 .4 2.2 1 .9 2 .2 2 .1 2 .2 Day 14 2.1 2.3 2.1 1.9 2.2 2.7 2.1 2.3 2.4 1.9 2.2 2.0 2.4 2.1 2.4 2.3 2.1 2.5 2.4 2.4 2.4 2.2 2.6 2.5 2.2 2.5 2.6 2 .6 2.0 2.2 2.7 2.4 2.4 2.1 2.2 2.7 2.4 2.3 2.3 2.6 2.5 2.1 2.5 2.4 2.4 Day 15 2.1 2.3 2.1 1.9 2.2 2.7 2.1 2.3 2.4 1.9 2.2 2.0 2.4 2.1 2.4 2.3 2.1 2.5 2.4 2.4 2.4 2.2 2.6 2.5 2.2 2.5 2.6 2.6 2.0 2.2 2.7 2.4 2.4 2.1 2.2 2.7 2.4 2.3 2.3 2.6 2.5 2.1 2.5 2.4 2.4 INDIVIDUAL DOSE VOLUMES (mL) Day 16 Day 17 Day 18 Day 19 2.1 2.1 2 .1 2.1 2.3 2.3 2 .3 2.3 2.1 2.1 2 .1 2.1 1.9 1.9 1 .9 1.9 2.2 2.2 2 .2 2.2 2.7 2.7 2 .7 2.7 2.1 2.1 2 .1 2.1 2.3 2.3 2 .3 2.3 2.4 2.4 2 .4 2.4 1.9 1.9 1 .9 1.9 2.2 2.2. 2 .2 2.2 2.0 2.0 2 .0 2.0 2.4 2.4 2 .4 2.4 2.1 2.1 2 .1 2.1 2.4 2.4 2 .4 2.4 2.3 2.3 2 .3 2.3 2.1 2.1 2 .1 2.1 2.5 2.5 2 .5 2.5 2.4 2.4 2 .4 2.4 2.4 2.4 2 .4 2.4 2.4 2.4 2.4 2.4 2.2 2.2 2.2 2.2 2.6 2.6 2 .6 2.6 2.5 2.5 2 .5 2.5 2.2 2.2 2 .2 2.2 2.5 2.5 2 .5 2.5 2.6 2.6 2 .6 2.6 2.6 2.6 2 .6 2.6 2.0 2.0 2 .0 2.0 2.2 2.2 2 .2 2.2 2.7 2.7 2 .7 2.7 2.4 2.4 2 .4 2.4 2.4 2.4 2 .4 2.4 2.1 2.1 2 .1 2.1 2.2 2.2 2 .2 2.2 2.7 2.7 2 .7 2.7 2.4 2.4 2 .4 2.4 2.3 2.3 2 .3 2.3 2.3 2.3 2 .3 2.3 2.6 ' 2.6 2 .6 2.6 2.5 2.5 2 .5 2.5 2.1 2.1 2 .1 2.1 2.5 2.5 2 .5 2.5 2.4 2.4 2 .4 2.4 2.4 2.4 2 .4 2.4 Day 20 2.1 2.3 2.1 1.9 2.2 2.7 2.1 2.3 2.4 1.9 2.2 2.0 2.4 2.1 2.4 2.3 2.1 2.5 2.4 2.4 2.4 2.2 2.6 2.5 2.2 2.5 2.6 2.6 2.0 2.2 2.7 2.4 2.4 2.1 2.2 2.7 2.4 2.3 2.3 2.6 2.5 2.1 2.5 2.4 2.4 Day 21 2 .4 2 .4 2 .2 2 .1 2 .6 2 .7 2 .3 2 .4 2 .5 2 .1 2 .3 2 .2 2 .7 2.2 2 .5 2 .5 2 .3 2 .6 2 .5 2 .5 2 .7 2 .3 2 .6 2 .6 2 .3 2 .8 2 .9 2 .8 2 .1 2 .4 2 .9 2 .6 2 .6 2 .3 2.4 2 .8 2 .7 2 .5 2 .6 2.7 2 .7 2.2 2 .7 2 .5 2 .6 Day 22 2. 2. 2. 2. 2 2 2. 2. 2. 2. 2. 2. 2 2 2 2 2 2 2 2 2 2 2 2 2 2 2 2 2 2 2 2 2 2 2 2 2 2 2 2 2 2 2 2 2 534 Company Sanitized. Does not contai H-24516: Subchronic Toxicity 90-Day Gavage Study in Rats with One-Generation Reproduction Evaluations Day 24 Day 25 Female, 643477 643374 643406 643486 643361 643463 643398 643436 643362 643354 643402 643383 643465 643484 643384 643352 643343 643459 643394 643480 643319 643350 643363 643397 643421 643420 643419 643414 643401 643455 643378 643393 643447 643478 643386 643405 643425 643448 643426 643415 643453 643330 643336 643387 643377 II-O ing/kg/day 2.4 2.4 2-4 2.4 2.2 2.2 2.1 2.1 2.6 2.6 2.7 2.7 2.3 2.3 2.4 2.4 2.5 2.5 2.1 2.1 2.3 2.3 2.2 2 .2 2.7 2.7 2.2 2.2 2.5 2.5 2.5 2.5 2.3 2.3 2.6 2.6 2.5 2.5 2.5 2.5 2.7 2.7 2.3 .2.3 2.6 2.6 2.6 2.6 2.3 2.3 2.8 2.8 2.9 2.9 2.8 2.8 2.1 2.1 2.4 2.4 2.9 2.9 2.6 2.6 2.6 2.6 2.3 2.3 2.4 2.4 2.8 2.8 2.7 2.7 2.5 2.5 2.6 2.6 2.7 2.7 2.7 2.7 2.2 2.2 2.7 2.7 2.5 2.5 2.6 2.6 Day 26 2.4 2.4 2.2 2.1 2.6 2.7 2.3 2.4 2.5 2.1 2.3 2.2 2-7 2.2 2.5 2.5 2.3 2.6 2.5 2.5 2.7 2.3 2.6 2.6 2.3 2.8 2.9 2.8 2.1 2.4 2.9 2.6 2.6 2.3 2.4 2.8 2 .7 2.5 2.6 2.7 2.7 2.2 2.7 2.5 2.6 Day 27 2.4 2.4 2.2 2.1 2.6 2.7 2.3 2.4 2.5 2.1 2.3 2.2 2.7 2.2 2.5 2.5 2.3 2.6 2.5 2.5 2.7 2.3 2.6 2.6 2.3 2.8 2.9 2.8 2.1 2.4 2.9 2.6 2 .6 2.3 2.4 2.8 2.7 2.5 2.6 2.7 2.7 2.2 2.7 2.5 2.6 INDIVI:DUAL DOE1E! VOLUMB!i (mL) Day 28 Day 29 Day 30 Day 31 2.4 2.4 2.4 2.4 2.5 2.5 2.5 2.5 2.3 2.3 2.3 2.3 2.1 2.1 2.1 2.1 2.7 2.7 2.7 2.7 2.9 2.9 2.9 2.9 2.4 2.4 2.4 2.4 2.6 2.6 2.6 2.6 2.6 2.6 2.6 2.6 2.2 2.2 2.2 2.2 2.4 2.4 2.4 2.4 2.2 2.2 2.2 2.2 2.8 2.8 2.8 2.8 2.3 2.3 2.3 2.3 2.6 2.6 2.6 2.6 2.6 2.6 2.6 2.6 2.4 2.4 2.4 2.4 2.7 2.7 2.7 2.7 2.7 2.7 2.7 2.7 2.7 2.7 2.7 2.7 2.7 2.7 2.7 2.7 2.4 2.4 2.4 2.4 2.9 2.9 2.9 2.9 2.7 2.7 2.7 2.7 2.4 2.4 2.4 2.4 2.9 2.9 2.9 2.9 3.1 3.1 3.1 3.1 2.9 2.9 2.9 2.9 2.3 2.3 2.3 2.3 2.6 2.6 2.6 2.6 3.0 ' 3.0 3.0 3.0 2.9 2.9 2.9 2.9 2.7 2.7 2-7 2.7 2.4 2.4 2.4 2.4 2.5 2.5 2.5 2.5 3.0 3.0 3.0 3.0 2.8 2.8 2.8 2.8 2.7 2.7 2.7 2.7 2.7 2.7 2.7 2.7 3.0 3.0 3.0 3.0 2.8 2.8 2.8 2.8 2.4 2.4 2.4 2.4 2.9 2.9 2.9 2.9 2.7 2.7 2.7 2.7 2.7 2.7 2.7 2.7 Day 32 2.4 2.5 2.3 2.1 2.7 2.9 2.4 2.6 2.6 2.2 2.4 2.2 2.8 2.3 2.6 2.6 2.4 2.7 2.7 2.7 2.7 2.4 2.9 2.7 2.4 2.9 3.1 2.9 2.3 2.6 3.0 2.9 2.7 2.4 2.5 3.0 2.8 2.7 2.7 3.0 2.8 2.4 2.9 2.7 2.7 Day 33 2.4 2.5 2.3 2.1 2.7 2.9 2.4 2.6 2.6 2.2 2.4 2.2 2.8 2.3 2.6 2.6 2.4 2.7 2.7 2.7 2.7 2.4 2.9 2.7 2.4 2.9 3.1 2.9 2.3 2.6 3.0 2.9 2.7 2.4 2.5 3.0 2.8 2.7 2.7 3.0 2.8 2.4 2.9 2.7 2.7 Day 3 2 2 2 2 2 2 2 2 2 2 2 2 2 2 2 2 2 2 2 2 2 2 2 2 2 2 3 2 2 2 3 2 2 2 2 3 2 2 2 3 2 2 2 2 2 535 CompanySanWzed. Does not c H-24516: Subchronic Toxicity . 90-Day Gavage Study in Rats with One-Generation Reproduction Evaluations Day 36 Day 37 Female, II - 0 ing/kg/day 643477 643374 643406 643486 643361 643463 643398 643436 643362 643354 643402 643383 643465 643484 643384 643352 643343 643459 643394 643480 643319 643350 643363 643397 643421 643420 643419 643414 643401 643455 643378 643393 643447 643478 643386 643405 643425 643448 643426 643415 643453 643330 643336 643387 643377 2 .6 2 .6 2 .4 2 .2 2 .8 3 .1 2 .6 2 .7 2 . s 2 .3 2 .5 2 .4 2 .7 2.4 2 .8 2 .8 2 .6 2 .9 2 .8 2 .9 2 .9 2 .5 3 .0 2 .8 2 .5 3 .2 3 .2 3 .1 2 .3 2 .6 3 .2 3 .0 2 .9 2 .4 2 .5 3 .2 2 .9 2 .8 2 .9 3 .0 2 .9 2 .5 3 .0 2 .9 2.9 2 .6 2 .6 2 .4 2 .2 2 .8 3 .1 2 .6 2 .7 2 .8 2 .3 2 .5 2 .4 2 .7 2.4 2 .8 2 .8 2 .6 2 .9 2 .8 2 .9 2 .9 -2 .5 3 .0 2 .8 2 .5 3 .2 3 .2 3 .1 2 .3 2 .6 3 .2 3 .0 2 .9 2 .4 2 .5 3 .2 2 .9 2 .8 2 .9 3 .0 2 .9 2 .5 3 .0 2 .9 2 .9 Day 38 2. 0 1. 9 1. 8 1. 7 2. 1 2. 3 2. 0 2. 0 2. 1 1. 7 1. 9 1. 8 2. 1 1. 8 2. 1 2. 1 2. 0 2. 1 2. 1 2. 2 2. 2 1. 9 2. 3 2. 1 1. 9 2. 4 2.4 2. 3 1. 8 1. 9 2. 4 2. 3 2. 2 1. 8 1. 9 2. 4 2. 2 2. 1 2. 2 2. 2 2. 2 1. 9 2. 2 2. 2 2. 1 Day 39 INDIVIDUAL DOSE VOLUMES (mL) Day 40 Day 41 Day 42 2.0 2 .0 2 .0 2.0 1.9 1 .9 1 .9 2.0 1.8 1 .8 1 .8 1.8 1.7 1 .7 1 .7 1.7 2.1 2 .1 2 .1 b 2.2 2.3 2 .3 2 .3 2.3 2.0 2 .0 2 .0 2.0 2.0 2 .0 2 .0 2.1 2.1 2 .1 2 .1 2.1 1.7 1 .7 1 .7 1.8 1.9 1 .9 1 .9 1.9 1.8 1 .8 1 .8 1.8 2.1 2 .1 2 .1 2.2 1.8 1 .8 1 .8 1.8 2.1 2 .1 2 .1 2.0 2.1 2 .1 2 .1 2.1 2.0 2 .0 2 .0 2.0 2.1 2 .1 2 .1 2.3 2.1 2 .1 2 .1 2.1 2.2 2 .2 2 .2 2.1 2.2 2 .2 2 .2 2.3 1.9 1 .9 1 .9 2.0 2.3 2 .3 2 .3 2.2 2.1 2 .1 2 .1 2.2 1-9 1 .9 1 .9 2.0 2.4 2 .4 2 .4 2.5 2.4 2 .4 2.4 2.5 2.3 2 .3 2 .3 2.4 1.8 1 .8 1 .8 1.8 1.9 1 .9 1 .9 2.0 2.4 2.4 2 .4 2.4 2.3 2 .3 2 .3 2.3 2.2 2 .2 2.2 2.2 1.8 1 .8 1 .8 1.9 1.9 1 .9 1 .9 2.0 2.4 2 .4 2 .4 2.6 2.2 2 .2 2 .2 2.2 2.1 2 .1 2 .1 2.1 2.2 2 .2 2 .2 2.2 2.2 2 .2 2 .2 2.3 2.2 2 .2 2 .2 2.3 1.9 1 .9 1 -9 2.0 2.2 2 .2 2.2 2.3 2.2 2 .2 2 .2 2.2 2.1 2 .1 2 .1 2.2 Day 43 2 .0 2 .0 1 .8 1 .7 2 .2 2 .3 2 .0 2 .1 2 .1 1 .8 1 .9 1 .8 2 .2 1 .8 2 .0 2 .1 2 .0 2 .3 2 .1 2 .1 2 .3 2 .0 2 .2 2 .2 2 .0 2 .5 2 .5 2 .4 1 .8 2 .0 2 .4 2 .3 2.2 1 .9 2 .0 2 .6 2 .2 2 .1 2 .2 2 .3 2 .3 2 .0 2 .3 2 .2 2.2 Day 44 2 .0 2 .0 1 .8 1 .7 2.2 2 .3 2 .0 2 .1 2 .1 1 .8 1 .9 1 .8 2 .2 1 .8 2 .0 2 .1 2 .0 2 .3 2 .1 2 .1 2 .3 2 .0 2 .2 2 .2 2 .0 2 .5 2 .5 2 .4 1 .8 2 .0 2 .4 2 .3 2 .2 1 .9 2 .0 2 .6 2 .2 2 .1 2 .2 2 .3 2 .3 2 .0 2 .3 2 .2 2 .2 536 Gonpwqr Smfflzed. Doe* not con H-24516: Subchronic Toxicity 90-Day Gavage Study in Rats with One-Generation Reproduction Evaluations Day 46 Day 47 Female, II - 0 mg/kg/day 643477 2 .0 2.0 643374 2 .0 2.0 643406 1 .8 1.8 6434B6 1 .7 1.7 643361 2 .2 2.2 643463 2 .3 2.3 643398 2 .0 2.0 643436 2 .1 2.1 643362 2 .1 2.1 643354 1 .8 1.8 643402 1 .9 1.9 643383 1 -8 1.8 643465 2 .2 2.2 643484 1 .8 1.8 643384 2 .0 2.0 643352 2 .1 2.1 643343 2 .0 2.0 643459 2 .3 2.3 643394 2 .1 2.1 643480 2 .1 2.1 643319 2 .3 2.3 643350 2 .0 2.0 643363 2 .2 2.2 643397 2 .2 2.2 643421 2 .0 2.0 643420 2 .5 2.5 643419 2 .5 2.5 643414 2 .4 2.4 643401 1 .8 1.8 643455 2 .0 2.0 643378 2 .4 2.4 643393 2 .3 2.3 643447 2 .2 2.2 643478 1 .9 1.9 643386 2 .0 2.0 643405 2 .6 2.6 643425 2.2 2.2 643448 2 .1 2.1 643426 2 .2 2.2 643415 2 .3 2.3 643453 2 .3 2.3 643330 2 .0 2.0 643336 2 .3 2.3 643387 2 .2 2.2 643377 2 .2 2.2 Day 48 2.0 2.0 1.8 1.7 2.2 2.3 2.0 2.1 2.1 1.8 1.9 1.8 2.2 1.8 2.0 2.1 2.0 2.3 2.1 2.1 2.3 2.0 2.2 2.2 2.0 2.5 2.5 2.4 1.8 2.0 2.4 2.3 2.2 1.9 2.0 2.6 2.2 2.1 2.2 2.3 2.3 2.0 2.3 2.2 2.2 INDIVIDUAL DOSE VOLUMES (mL) Day 49 Day 50 Day 51 Day 52 2.0 2.0 2.0 2.0 2.1 2.1 2.1 2.1 1.9 1.9 1.9 1.9 1.8 1.8 1.8 1.8 2.4 2.4 2.4 2.4 2.3 2.3 2.3 2.3 2.0 2.0 2.0 2.0 2.1 2.1 2.1 2.1 2.1 2.1 2.1 2.1 1.9 1.9 1.9 1.9 2.0 2.0 2.0 2.0 1.9 1.9 1.9 1.9 2.2 2.2 2.2 2.2 1.9 1.9 1.9 1.9 2.1 2.1 2.1 2.1 2.2 2.2 2.2 2.2 2.1 2.1 2.1 2.1 2.4 2.4 2.4 2.4 2.2 2.2 2.2 2.2 2.2 2.2 2.2 2.2 2.3 2.3 2.3 2.3 2.1 2.1 2.1 2.1 2.4 2.4 2.4 2.4 2.3 2.3 2.3 2.3 2.0 2.0 2.0 2.0 2.6 2.6 2.6 2.6 2.6 2.6 2.6 2 .6 2.5 2.5 2.5 2.5 1.8 1.8 1.8 1.8 2.0 2.0 2.0 2.0 2.6 2.6 2.6 2.6 2.4 2.4 2.4 2.4 2.3 2.3 2.3 2.3 2.0 2.0 2.0 2.0 2.0 2.0 2.0 2.0 2.7 2.7 2.7 2.7 2.3 2.3 2.3 2.3 2.1 2 .1 2.1 2.1 2.3 2.3 2.3 2.3 2.4 2.4 2.4 2.4 2.4 2.4 2.4 2.4 2.0 2.0 2.0 2.0 2.4 2.4 2.4 2.4 2.3 2.3 2.3 2.3 2.3 2.3 2.3 2.3 Day 53 2.0 2.1 1.9 1.8 2.4 2.3 2.0 2.1 2.1 1.9 2.0 1.9 2.2 1.9 2.1 2.2 2.1 2.4 2.2 2.2 2.3 2.1 2.4 2.3 2.0 2.6 2.6 2.5 1.8 2.0 2.6 2.4 2.3 2.0 2.0 2.7 2.3 2.1 2.3 2.4 2.4 2.0 2.4 2.3 2.3 Day 54 2 .0 2 .1 1 .9 1 .8 2 .4 2 .3 2 .0 2 .1 2 .1 1 .9 2 .0 1 .9 2 .2 1 .9 2 .1 2 .2 2 .1 2 .4 2 .2 2 .2 2 .3 2 .1 2.4 2 .3 2 .0 2 .6 2 .6 2 .5 1 .8 2 .0 2 .6 2 .4 2 .3 2 .0 2 .0 2 .7 2 .3 2 .1 2 .3 2 .4 2 .4 2 .0 2 .4 2 .3 2 .3 537 >co H-24516: Subchronic Toxicity 90-Day Gavage Study in Rats with One-Generation Reproduction Evaluations Day 56 Day 57 Female, II - 0 mg/kg/day 643477 2.0 2 .0 643374 2.1 2 .1 643406 1.9 1 .9 643486 1.9 1 .9 643361 2.5 2 .5 643463 2.5 2 .5 643398 2.2 2 .2 643436 2.2 2 .2 643362 2.2 2 .2 643354 2.0 2 .0 643402 2.0 2 .0 643383 2.1 2 .1 643465 2.3 2 .3 643484 1.9 1 .9 643384 2.1 2 .1 643352 2.3 2 .3 643343 2.1 2 .1 643459 2.4 2 .4 643394 2.1 2 .1 643480 2.3 2 .3 643319 2.4 2 .4 643350 2.1 2 .1 643363 2.5 2 .5 643397 2.2 2 .2 643421 2.1 2 .1 643420 2.6 2 .6 643419 2.7 2 .7 643414 2.6 2 .6 643401 2.0 2 .0 643455 2.1 2 .1 643378 2.5 2 .5 643393 2.5 2 .5 643447 2.3 2 .3 643478 2.0 2 .0 643386 2.1 2 .1 643405 2.7 2 .7 643425 2.4 2 .4 643448 2.3 2 .3 643426 2.4 2 .4 643415 2.4 2 .4 643453 2.4 2.4 643330 2.0 2 .0 643336 2.4 2.4 643387 2.4 2 .4 643377 2.4 2 .4 Day 58 2.0 2.1 1.9 1.9 2.5 2.5 2.2 2.2 2.2 2.0 2.0 2.1 2.3 1.9 2.1 2.3 2.1 2 .4 2.1 2.3 2.4 2.1 2.5 2.2 2.1 2.6 2.7 2.6 2.0 2.1 2.5 2.5 2.3 2.0 2.1 2.7 2.4 2.3 2.4 2.4 2.4 2.0 2.4 2.4 2.4 INDIVIDUAL DOSE VOLUMES Day 59 Day 60 Day 61 (mL) Day 62 2.0 2.0 2.0 2.0 2.1 2.1 2.1 2.1 1.9 1.9 1.9 1.9 1.9 1.9 1.9 1.9 2.5 2.5 2.5 2.5 2.5 2.5 2.5 2.5 2.2 2.2 2.2 2.2 2.2 2.2 2.2 2.2 2.2 2.2 2.2 2.2 2.0 2.0 2.0 2.0 2.0 2.0 2.0 2.0 2.1 2.1 2.1 2.1 2.3 2.3 2.3 2.3 1.9 1.9 1.9 1.9 2.1 2.1 2.1 2.1 2.3 2.3 2.3 2.3 2.1 2.1 2.1 2.1 2.4 2.4 2.4 2 .4 2.1 2.1 2.1 2.1 2.3 2.3 2.3 2.3 2.4 2.4 2.4 2.4 2.1 2.1 2.1 2.1 2.5 2.5 2.5 2.5 2.2 2.2 2.2 2.2 2.1 2.1 2.1 2.1 2.6 2.6 2.6 2.6 2.7 2.7 2.7 2.7 2.6 2.6 2.6 2.6 2.0 2.0 2.0 2.0 2.1 2.1 2.1 2.1 2.5 2.5 2.5 2.5 2.5 2.5 2.5 2.5 2.3 2.3 2.3 2.3 2.0 2.0 2.0 2.0 2.1 2.1 2.1 2.1 2.7 2.7 2.7 2.7 2.4 2.4 2.4 2.4 2.3 2.3 2.3 2.3 2.4 2.4 2.4 2.4 2.4 2.4 2.4 2.4 2.4 2.4 2.4 2.4 2.0 2.0 2.0 2.0 2.4 2.4 2.4 2.4 2.4 2.4 2.4 2.4 2.4 2.4 2.4 2.4 Day 63 2.1 2.2 2.0 2.0 2.6 2.5 2.2 2.2 2.3 2.0 2.0 2.1 2.3 1.9 2.2 2.2 2.0 2.3 2.2 2.2 2.4 2.2 2.5 2.2 2.1 2.7 2.7 2.6 1.9 2.1 2.6 2.5 2.4 2.0 2.1 2.7 2.4 2.3 2.4 2.6 2.4 2.1 2.5 2.4 2.5 Day 64 2. 1 2. 2 2. 0 2. 0 2. 6 2. 5 2. 2 2. 2 2. 3 2. 0 2. 0 2. 1 2. 3 1. 9 2. 2 2. 2 2. 0 2. 3 2.2 2. 2 2. 4 2. 2 2. 5 2. 2 2. 1 2. 7 2. 7 2. 6 1. 9 2. 1 2. 6 2. 5 2.4 2. 0 2. 1 2. 7 2. 4 2. 3 2..4 2. 6 2..4 2.,1 2..5 2.,4 2,.5 538 Company Sanitized. Does no H-24516: Subchronic Toxicity 90-Day Gavage Study in Rats with One-Generation Reproduction Evaluations Day 66 Day 67 Female, II - 0 mg/kg/day 643477 2.1 2.1 643374 2.2 2.2 643406 2.0 2.0 643486 2.0 2.0 643361 2.6 2.6 643463 2.5 2.5 643398 2.2 2.2 643436 2.2 2.2 643362 2.3 2.3 643354 2.0 2.0 643402 2.0 2.0 643383 2.1 2.1 643465 2.3 2.3 643484 1.9 1.9 643384 2.2 2.2 643352 2.2 2.2 643343 2.0 2.0 643459 2.3 2.3 643394 2.2 2.2 643480 2.2 2.2 643319 2.4 2.4 643350 2.2 2.2 643363 2.5 2.5 643397 2.2 2.2 643421 2.1 2.1 643420 2.7 2.7 643419 2.7 2.7 643414 2.6 2.6 643401 1.9 1.9 643455 2.1 2.1 643378 2.6 2.6 643393 2.5 2.5 643447 2.4 2.4 643478 2.0 2.0 643386 2.1 2.1 643405 2.7 2.7 643425 2.4 2.4 643448 2.3 2.3 643426 2.4 2.4 643415 2.6 2.6 643453 2.4 2.4 643330 2.1 2.1 643336 2.5 2.5 643387 2.4 2.4 643377 2.5 2.5 Day 68 2.1 2.2 2.0 2.0 2.6 2.5 2.2 2.2 2.3 2.0 2.0 2.1 2.3 1.9 2.2 2.2 2.0 2.3 2.2 2.2 2.4 2.2 2.5 2.2 2.1 2.7 2.7 2.6 1.9 2.1 2.6 2.5 2.4 2.0 2.1 2.7 2.4 2.3 2.4 2.6 2.4 2.1 2.5 2.4 2.5 INDIVIDUAL DOSE VOLUMES (mL) Day 69 Day 70 Day 71 Day 72 2.1 2.1 2.1 2.1 2.2 2.3 2.3 2.3 2.0 2.1 2.1 2.1 2.0 2.0 2.0 2.0 2.6 2.6 2.6 2.6 2.5 2.5 2.5 2.5 2.2 2.2 2.2 2.2 2.2 2.2 2.2 2.2 2,3 2.3 2.3 2.3 2.0 2.1 2.1 2.1 2.0 2.1 2.1 2.1 2.1 2.2 2.2 2.2 2.3 2.4 2.4 2.4 1.9 1.9 1.9 1.9 2.2 2.2 2.2 2.2 2.2 2.3 2.3 2.3 2.0 2.2 2.2 2.2 2.3 2.4 2.4 2.4 2.2 2.2 2.2 2.2 2.2 2.2 2.2 2.2 2.4 2.4 2.4 2.4 2.2 2.2 2.2 2.2 2.5 2.5 2.5 2.5 2.2 2.3 2.3 2.3 2.1 2.1 2.1 2.1 2.7 2.7 2.7 2.7 2.7 2.7 2.7 2.7 2.6 2.7 2.7 2.7 1.9 2.0 2.0 2 .0 2.1 2.1 2.1 2.1 2.6 2.6 2.6 2.6 2.5 2.5 2.5 2.5 2.4 2.4 2.4 2.4 2.0 2.0 2.0 2.0 2.1 2.1 2.1 2.1 2.7 2.8 2.8 2.8 2.4 2.4 2.4 2.4 2.3 2.3 2.3 2.3 2.4 2.5 2.5 2.5 2.6 2.8 2.8 2.8 2.4 2.5 2.5 2.5 2.1 2.1 2.1 2.1 2.5 2.5 2.5 2.5 2.4 2.5 2.5 2.5 2.5 2.5 2.5 2.5 Day 73 2.1 2.3 2.1 2.0 2.6 2.5 2.2 2.2 2.3 2.1 2.1 2.2 2.4 1.9 2.2 2.3 2.2 2.4 2.2 2.2 2.4 2.2 2.5 2.3 2.1 2.7 2.7 2.7 2.0 2.1 2.6 2.5 2.4 2.0 2.1 2.8 2.4 2.3 2.5 2.8 2.5 2.1 2.5 2.5 2.5 Day 74 2. 1 2. 3 2. 1 2. 0 2. 6 2. 5 2. 2 2. 2 2. 3 2. 1 2. 1 2. 2 2. 4 1. 9 2. 2 2. 3 2. 2 2. 4 2. 2 2. 2 2. 4 2. 2 2. 5 2. 3 2. 1 2. 7 2. 7 2. 7 2. 0 2. 1 2. 6 2. 5 2. 4 2. 0 2. 1 2..8 2..4 2..3 2.,5 2,.8 2 .5 2..1 2 .5 2 .5 2 .5 539 COBn<nySanitized. "o-- not cont H-24516: Subchronic Toxicity 90-Day Gavage Study in Rats with One-Generation Reproduction Evaluations Female, 643477 643374 643406 643486 643361 643463 643398 643436 643362 643354 643402 643383 643465 643484 643384 643352 643343 643459 643394 643480 643319 643350 643363 643397 643421 643420 643419 643414 643401 643455 643378 643393 643447 643478 643386 643405 643425 643448 643426 643415 643453 643330 643336 643387 643377 Day 76 Day 77 II - 0 mg/kg/day 2 .1 2.1 2 .3 2.3 2 .1 2.0 2 .0 2.0 2 .6 2.7 2 .5 2.5 2 .2 2.2 2 .2 2.3 2 .3 2.3 2 .1 2.1 2 .1 2.0 2 .2 2.2 2.4 2.4 1 .9 2.0 2 .2 2.3 2 .8 2.7 2 .4 2.4 2 .3 2.3 2 .5 2.6 2 .8 2.9 2 .5 2.5 2 .1 2.1 2 .5 2.5 2 .5 2.5 2 .5 2.6 Day 78 2.1 2.3 2.0 2.0 2.7 2.5 2.2 2.3 2.3 2.1 2.0 2.2 2.4 2.0 2.3 2.7 2.4 2.3 2.6 2.9 2.5 2.1 2.5 2.5 2.6 INDIVIDUAL DOSE VOLUMES Day 79 Day 80 Day 81 (mL) Day 82 2.1 2.1 2.1 2.1 2.3 2.3 2.3 2.3 2.0 2.0 2.0 2.0 2.0 2.0 2.0 2.0 2.7 2.7 2.7 2.7 2.5 2.5 2.5 2.5 2.2 2.2 2.2 2.2 2.3 2.3 2.3 2.3 2.3 2.3 2.3 2.3 2.1 2.1 2.1 2.1 2.0 2.0 2.0 2.0 2.2 2.2 2.2 2.2 2.4 2.4 2.4 2.4 2.0 2.0 2.0 2.0 2.3 2.3 2.3 2.3 2.7 2.7 2.7 2.7 2.4 2 .4 2.4 2.4 2.3 2.3 2.3 2.3 2.6 2.6 2.6 2.6 2.9 2.9 2.9 2.9 2.5 2.5 2.5 2.5 2.1 2.1 2.1 2.1 2.5 2.5 2.5 2.5 2.5 2.5 2.5 2.5 2.6 2.6 2.6 2.6 Day 83 2.1 2.3 2.0 2.0 2.7 2.5 2.2 2.3 2.3 2.1 2.0 2.2 2.4 2.0 2.3 2.7 2.4 2.3 2.6 2.9 2.5 2.1 2.5 2.5 2.6 Day 84 2.2 2.4 2.0 1.9 2.8 2.6 2.3 2.3 2.4 2.1 2.1 2.2 2.4 2.0 2.3 2.7 2.4 2.3 2.6 3.0 2.5 2.2 2.5 2.5 2.5 540 Company SanfHzed. Does not contain H-24516: Subchronic Toxicity 90-Day Gavage Study in Rats with One-Ggneration Reproduction Evaluations Day 86 Day 87 Female, II - 643477 643374 643406 643486 643361 643463 643398 643436 643362 643354 643402 643383 643465 643484 643384 643352 643343 643459 643394 643480 643319 643350 643363 643397 643421 643420 643419 643414 643401 643455 643378 643393 643447 643478 643386 643405 643425 643448 643426 643415 643453 643330 643336 643387 643377 0 nig/kg/day 2.2 2.4 2.0 1.9 2.8 2.6 2.3 2.3 2.4 2.1 2.1 2.2 2.4 2.0 2.3 2.7 2.4 2.3 2.6 3.0 2.5 2.2 2.5 2.5 2.5 2. 2 2.4 2. 0 1. 9 2. 8 2. 6 2. 3 2. 3 2. 4 2. 1 2. 1 2. 2 2.4 2. 0 2.,3 2 .7 2 .4 2 .3 2 .6 3 .0 2 .5 2 .2 2 .5 2 .5 2 .5 Day 88 2.2 2.4 2.0 1.9 2.8 2.6 2.3 2.3 2.4 2.1 2.1 2.2 2.4 2.0 2.3 2.7 2.4 2.3 2.6 3.0 2.5 2.2 2.5 2.5 2.5 .INDIVIDUAL DOSE VOLUMES Day 89 Day 90 Day 91 (mL) Day 92 2.2 2.2 2.2 2.2 2.4 2.4 2.5 2.5 2.0 2.0 2.1 2.1 1.9 1.9 1.9 1.9 2.8 2.8 3.0 3.0 2.6 2.6 2.6 2.6 2.3 2.3 2.3 2.3 2.3 2.3 2.4 2.4 2.4 2.4 2.3 2.3 2.1 2.1 2.2 2.2 2.1 2.2 2.4 2.0 2.3 2.7 2.4 2.3 2.6 3.0 2.5 2.2 2.5 2.5 2.5 541 Company Sanl^ed. Does not con H-24516: Subchronic Toxicity 90-Day Gavage Study in Rats with One-Generation Reproduction Evaluations Day 0 Day 1 Day 2 Female, IV - 25 ing/kg/day 643390 643396 643380 643433 643389 643410 643321 643324 64345B 643364 643483 643411 643379 643391 643437 643399 643334 643464 643369 643490 643342 643438 643445 643418 643325 643479 643403 643376 643422 643452 643475 643372 643400 643395 643457 1.8 1.8 1.8 2.0 2.0 2.0 1.7 1.7 1.7 1.9 1.9 1.9 1.8 1.8 1.8 1.9 1.9 1.9 1.9 1.9 1.9 1.8 1.8 1.8 1.8 1.8 1.8 1.8 1.8 1.8 1.8 1.8 1.8 1.7 AK TEST DAY 0 2.1 2.1 2.1 1.7 1.7 1.7 1.9 1.9 1.9 1.8 1.8 1.8 1.7 1.7 1.7 2.1 2.1 2.1 2.0 2.0 2.0 2.1 2.1 2.1 2.0 2.0 2.0 2.0 2.0 2.0 2.3 "2.3 2.3 1.9 1.9 1.9 2.2 2.2 2.2 1.9 1.9 1.9 1.9 1.9 1.9 1.9 1.9 1.9 2.0 2.0 2.0 2.1 2.1 2.1 2.2 2.2 2.2 2.0 2.0 2.0 1.7 1.7 1.7 1.9 1.9 1.9 2.0 2.0 2.0 Day 3 1.8 2.0 1.7 1.9 1.8 1.9 1.9 1.8 1.8 1.8 1.8 2.1 1.7 1.9 1.8 1.7 2.1 2.0 2.1 2.0 2.0 2.3 1.9 2.2 1.9 1.9 1.9 2.0 2.1 2.2 2.0 1.7 1.9 2.0 INDIV3:E)UAL DOESE! VOLUMIii (mL) Day 4 Day 5 Day 6 Day 7 1.8 1.8 1.8 1.9 2.0 2.0 2.0 2.3 1.7 1.7 1.7 1.9 1.9 1.9 1.9 2.2 1.8 1.8 1.8 2.1 1.9 1.9 1.9 2.3 1.9 1.9 1.9 2.1 1.8 1.8 1.8 2.0 1.8 1.8 1.8 1.9 1.8 1.8 1.8 1.9 1.8 1.8 1.8 2.0 2.1 2.1 2.1 2.2 1.7 1.7 1.7 1.9 1.9 1.9 1.9 2.0 1.8 1.8 1.8 2.0 1.7 1.7 1.7 1.9 2.1 2.1 2.1 2.4 2.0 2.0 2.0 2.2 2.1 2.1 2.1 2.3 2.0 2.0 2.0 2.3 2.0 2.0 2.0 2.2 2.3 2.3 2.3 2.6 1.9 1.9 1.9 2.1 2.2 2.2 2.2 2.5 1.9 1.9 1.9 2.2 1.9 1.9 1.9 2.3 1.9 1.9 1.9 2.2 2.0 2.0 2.0 2.3 2.1 2.1 2.1 2.2 2.2 2.2 2.2 2.5 2.0 2.0 2.0 2.2 1.7 1.7 1.7 1.9 1.9 1.9 1.9 2.1 2.0 2.0 2.0 2.3 Day 8 1.9 2.3 1.9 2.2 2.1 2.3 2.1 2.0 1.9 1.9 2.0 2.2 1.9 2.0 2.0 1.9 2.4 2.2 2.3 2.3 2,2 2.6 2.1 2.5 2.2 2.3 2.2 2.3 2.2 2.5 2.2 1.9 2.1 2.3 Day 9 1.9 2.3 1.9 2.2 2.1 2.3 2.1 2.0 1.9 1.9 2.0 2.2 1.9 2.0 2.0 1.9 2.4 2.2 2.3 2.3 2.2 2.6 2.1 2.5 2.2 2.3 2.2 2.3 2.2 2.5 2.2 1.9 2.1 2.3 Day 1 1 2 1 2 2 2 2 2 1 1 2 2 1 2 2 1 2 2 2 2 2 2 2 2 2 2 2 2 2 2 2 2 2 542 Company Sanitized. Does not H-24516: Subchronic Toxicity 90-Day Gavage Study in Rats with One-Generation Reproduction Evaluations Day 12 Day 13 Female, 643390 643396 643380 643433 643389 643410 643321 643324 643458 643364 643483 643411 643379 643391 643437 643399 643334 643464 643369 643490 643342 643438 643445 643418 643325 643479 643403 643376 643422 643452 643475 643372 643400 643395 643457 IV - 25 m9/k9/day 1 .9 2 .3 1 .9 2 .2 2 .1 2 .3 2 .1 2 .0 1 .9 1 .9 2 .0 2 .2 1 .9 2 .0 2 .0 1 .9 2 .4 2 .2 2 .3 2 .3 2 .2 2 .6 2 .1 2 .5 2 .2 2 .3 2 .2 2 .3 2 .2 2 .5 2 .2 1 .9 2 .1 2 .3 1. 9 2. 3 1. 9 2. 2 2. 1 2. 3 2. 1 2. 0 1. 9 1. 9 2. 0 2.2 1. 9 2. 0 2. 0 1. 9 2. 4 2. 2 2 .3 2. 3 -2. 2 2. 6 2. 1 2. 5 2. 2 2 .3 2. 2 2. 3 2.2 2. 5 2. 2 1. 9 2. 1 2.,3 Day 14 2.0 2.5 2.3 2.4 2.2 2.4 2.1 2.2 2.2 2.1 2.1 2.4 2.1 2.2 2.3 2.1 2.6 2.4 2.5 2.5 2.4 2.7 2.3 2.7 2.3 2.5 2.4 2.6 2.4 2.5 2.4 2.0 2.3 2.5 Day 15 2 .0 2 .5 2 .3 2 .4 2 .2 2 .4 2 .1 2 .2 2 .2 2 .1 2 .1 2 .4 2 .1 2 .2 2 .3 2 .1 2 .6 2 .4 2 .5 2 .5 2 .4 2 .7 2 .3 2 .7 2 .3 2 .5 2.4 2 .6 2 .4 2 .5 2 .4 2 .0 2 .3 2 .5 INDIVIDUAL DOSE VOLUMES (mL) Day 16 Day 17 Day IS'1 Day 19 2.0 2 .0 2 .0 2.0 2.5 2 .5 2 .5 2.5 2.3 2 .3 2 .3 2.3 2.4 2 .4 2.4 2.4 2.2 2 .2 2 .2 2.2 2.4 2 .4 2 .4 2.4 2.1 2 .1 2 .1 2.1 2.2 2 .2 2 .2 2.2 2.2 2 .2 2 .2 2.2 2.1 2 .1 2 .1 2.1 2.1 2 .1 2 .1 2.1 2.4 2 .4 2 .4 2.4 2.1 2 .1 2 .1 2.1 2.2 2 .2 2 .2 2.2 2.3 2 .3 2 .3 2.3 2.1 2 .1 2 .1 2.1 2.6 2.6 2 .6 2.6 2.4 2.4 2 .4 2.4 2.5 2 .5 2 .5 2.5 2.5 2 .5 2 .5 2.5 2.4 2 .4 2 .4 2.4 2.7 2 .7 2 .7 2.7 2.3 2 .3 2 .3 2.3 2.7 2 .7 2 .7 2.7 2.3 2 .3 2 .3 2.3 2 .5 2 .5 2 .5 2.5 2.4 2 .4 2.4 2.4 2.6 2 .6 2 .6 2.6 2.4 2 .4 2 .4 2.4 2.5 2 .5 2 .5 2.5 2.4 2.4 2.4 2.4 2.0 2 .0 2 .0 2.0 2.3 2 .3 2 .3 2.3 2.5 2 .5 2 .5 2.5 Day 20 2 .0 2 .5 2 .3 2 .4 2 .2 2 .4 2 .1 2 .2 2.2 2 .1 2 .1 2 .4 2 .1 2 .2 2 .3 2 .1 2 .6 2.4 2 .5 2 .5 2 .4 2 .7 2 .3 2 .7 2 .3 2 .5 2.4 2 .6 2 .4 2 .5 2.4 2 .0 2 .3 2 .5 Day 21 2 .2 2 .8 2 .5 2 .7 2 .4 2 .6 2 .3 2 .4 2 .3 2 .3 2 .3 2 .7 2 .2 2 .5 2 .4 2 .4 2 .8 2 .6 2 .7 2 .7 2 .5 3 .0 2.4 3 .0 2 .6 2 .7 2 .6 2 .8 2 .7 2 .8 2.6 2 .1 2 .5 2.6 Day 2 2 2 2 2 2 2 2 2 2 2 2 2 2 2 2 2 2 2 2 2 3 2 3 2 2 2 2 2 2 2 2 2 2 543 "ompany SanWrad. Doe* noleon H-24516: Subchronic Toxicity 90-Day Gavage Study in Rats with One-Generation Reproduction Evaluations Day 24 Day 25 Female, IV - 25 ing/kg/day 643390 643396 643380 643433 643389 643410 643321 643324 64345B 643364 643483 643411 643379 643391 643437 643399 643334 643464 643369 643490 643342 643438 643445 643418 643325 643479 643403 643376 643422 643452 643475 643372 643400 643395 643457 2. 2 2.2 2. 8 2.8 2. 5 2.5 2. 7 2.7 2. 4 2.4 2. 6 2.6 2. 3 2.3 2. 4 2.4 2. 3 2.3 2. 3 2.3 2. 3 2.3 2. 7 2.7 2. 2 2.2 2. 5 2.5 2. 4 2.4 2. 4 2.4 2. 8 2.8 2. 6 2.6 2. 7 2.7 2. 7 2.7 2. 5 " 2.5 3. 0 3.0 2. 4 2.4 3. 0 3.0 2. 6 2.6 2. 7 2.7 2. 6 2.6 2. 8 2.8 2. 7 2.7 2. 8 2.8 2. 6 2.6 2. 1 2.1 2. 5 2.5 2. 6 2.6 Day 26 2.2 2.8 2.5 2.7 2.4 2.6 2.3 2.4 2.3 2.3 2.3 2.7 2.2 2.5 2.4 2.4 2.8 2.6 2.7 2.7 2.5 3.0 2.4 3.0 2.6 2.7 2.6 2.8 2.7 2.8 2.6 2.1 2.5 2.6 Day 27 2.2 2.8 2.5 2.7 2.4 2.6 2.3 2.4 2.3 2.3 2.3 2.7 2.2 2.5 2.4 2.4 2.8 2.6 2.7 2.7 2.5 3.0 2.4 3.0 2.6 2.7 2.6 2.8 2.7 2.8 2.6 2.1 2.5 2.6 INDIV]:r)UAL DOS E VOLUMI3S; (mL) Day 28 Day 29 Day 30 Day 31 2.4 2.4 2.4 2.4 2.8 2.8 2.8 2.8 2.7 2.7 2.7 2.7 2.9 2.9 2.9 2.9 2.4 2.4 2.4 2.4 2.7 2.7 2.7 2.7 2.4 2.4 SB TEST DAY 29 2.6 2.6 2.6 2.6 2.4 2.4 2.4 2.4 2.4 2.4 2.4 2.4 2.3 2.3 2.3 2.3 2.7 2.7 2.7 2.7 2.3 2.3 2.3 2.3 2.5 2.5 2.5 2.5 2.6 2.6 2.6 2.6 2.5 2.5 2.5 2.5 2.9 2.9 2.9 2.9 2.9 2.9 2.9 2.9 2.8 2.8 2.8 2.8 2.9 2.9 2.9 2.9 2.8 2.8 2.8 2.8 3.1 3.1 3.1 3.1 2.6 2.6 2.6 2.6 3.1 3.1 3.1 3.1 2.6 2.6 2.6 2.6 2.8 2.8 2.8 2.8 2.7 2.7 2.7 2.7 3.0 3.0 3.0 3.0 3.0 3.0 3.0 3.0 2.9 2.9 2.9 2.9 2.8 2.8 2.8 2.8 2.3 2.3 2.3 2.3 2.6 2.6 2.6 2.6 2.7 2.7 2.7 2.7 Day 32 2.4 2.8 2.7 2.9 2.4 2.7 2.6 2.4 2.4 2.3 2.7 2.3 2.5 2.6 2.5 2.9 2.9 2.8 2.9 2.8 3.1 2.6 3.1 2.6 2.8 2.7 3.0 3.0 2.9 2.8 2.3 2.6 2.7 Day 33 2.4 2.8 2.7 2.9 2.4 2.7 2.6 2.4 2.4 2.3 2.7 2.3 2.5 2.6 2.5 2.9 2.9 2.8 2.9 2.8 3.1 2.6 3.1 2.6 2.8 2.7 3.0 3.0 2.9 2.8 2.3 2.6 2.7 Day 3 2 2 2 2 2 2 2 2 2 2 2 2 2 2 2 2 2 2 2 2 3 2 3 2 2 2 3 3 2 2 2 2 2 544 Company SanWzed. Does not contain T H-24516: Subchronic Toxicity 90-Day Gavage Study in Rats with One-Generation Reproduction Evaluations Day 36 Day 37 Female, IV - 25 nig/kg/day 643390 643396 643380 643433 643389 643410 643321 643324 643458 643364 643483 643411 643379 643391 643437 643399 643334 643464 643369 643490 643342 643438 643445 643418 643325 643479 643403 643376 643422 643452 643475 643372 643400 643395 643457 2 .5 3 .0 2 .8 2 .9 2 .6 2 .9 2 .7 2 .6 2 .5 2 .5 2 .8 2.4 2 .6 2 .7 2 .6 3 .0 2 .9 2 .8 3 .0 2 .9 3 .5 2 .7 3 .2 2 .8 3 .0 2 .7 3 .1 3 .1 3 .0 2 .9 2.4 2 .7 2 .8 2 .5 3 .0 2 .8 2 .9 2 .6 2 .9 2 .7 2 .6 2 .5 2 .5 2 .8 2 .4 2 .6 2 .7 2 .6 3 .0 2 .9 2 .8 3 .0 ' 2 .9 3 .5 2 .7 3 .2 2 .8 3 .0 2 .7 3 .1 3 .1 3 .0 2 .9 2 .4 2 .7 2 .8 Day 38 1 .9 2 .3 2 .1 2 .2 2 .0 2 .2 2 .0 1 .9 1 .9 1 .9 2 .1 1 .8 2 .0 2 .0 2 .0 2 .3 2 .2 2 .1 2 .2 2 .1 2 .6 2 .0 2 .4 2 .1 2 .2 2 .1 2 .3 2 .3 2 .3 2 .1 1 .8 2 .0 2 .1 Day 39 INDIVIDUAL DOSE VOLUMES (mL) Day 40 Day 41 Day 42 1 .9 2 .3 2 .1 2 .2 2 .0 2.2 2 .0 1 .9 1 .9 1 .9 2 .1 1 .8 2 .0 2 .0 2 .0 2 .3 2.2 2 .1 2 .2 2 .1 2 .6 2 .0 2 .4 2 .1 2 .2 2 .1 2 .3 2 .3 2 .3 2 .1 1 .8 2 .0 2 .1 1 .9 2 .3 2 .1 2 .2 2 .0 2 .2 2 .0 1 .9 1 .9 1 .9 2 .1 1 .8 2 .0 2 .0 2 .0 2 .3 2 .2 2 .1 2.2 2 .1 2 .6 2 .0 2.4 2 .1 2 .2 2 .1 2 .3 2 .3 2 .3 ' 2 .1 , 1 .8 2 .0 2 .1 1 .9 2 .3 2 .1 2 .2 2 .0 2.2 2 .0 1 .9 1 .9 1 .9 2 .1 1 .8 2 .0 2 .0 2 .0 2 .3 2.2 2 .1 2 .2 2 .1 2 .6 2 .0 2 .4 2 .1 2 .2 2 .1 2 .3 2 .3 2 .3 2 .1 1 .8 2 .0 2 .1 1. 9 2. 3 2. 1 2. 3 2. 1 2. 3 2. 0 2. 0 1. 9 1. 9 2. 1 1. 9 2. 1 2. 1 2. 0 2. 4 2. 1 2. 2 2. 4 2.2 2. 8 2. 2 2. 5 2. 1 2. 3 2. 2 2. 4 2. 4 2. 5 2. 2 1. 9 2. 0 2. 2 Day 43 1 .9 2 .3 2 .1 2 .3 2 .1 2 .3 2 .0 2 .0 1 .9 1 .9 2 .1 1 .9 2 .1 2 .1 2 .0 2.4 2 .1 2 .2 2 .4 2.2 2 .8 2 .2 2 .5 2 .1 2 .3 2.2 2 .4 2 .4 2 .5 2 .2 1 .9 2 .0 2 .2 Day 44 1.9 2.3 2.1 2.3 2.1 2.3 2.0 2.0 1.9 1.9 2.1 1.9 2.1 2.1 2.0 2.4 2.1 2.2 2.4 2.2 2.8 2.2 2.5 2.1 2.3 2.2 2.4 2.4 2.5 2.2 1.9 2.0 2.2 545 Company Sanitized. Does not cont ^l? H-24516: Subchronic Toxicity 90-Day Gavage Study in Rats with One-Generation Reproduction Evaluations Day 46 Day 47 Female, IV - 25 nig/kg/day 643390 1 .9 643396 2 .3 643380 2 .1 643433 2 .3 643389 2 .1 643410 2 .3 643321 643324 2 .0 643458 2 .0 643364 1 .9 643483 1 .9 643411 643379 2 .1 643391 1 .9 643437 2 .1 643399 2 .1 643334 2 .0 643464 2.4 643369 2 .1 643490 2 .2 643342 2 .4 643438 2 .2 643445 2 .8 643418 2 .2 643325 2 .5 643479 2 .1 643403 2 .3 643376 2 .2 643422 2.4 643452 2 .4 643475 2 .5 643372 2 .2 643400 1 .9 643395 2 .0 643457 2 .2 1 .9 2 .3 2 .1 2 .3 2 .1 2 .3 2 .0 2 .0 1 .9 1 .9 2 .1 1 .9 2 .1 2 .1 2 .0 2 .4 2 .1 2 .2 2 .4 2 .2 2 .8 2 .2 2 .5 2 .1 2 .3 2 .2 2.4 2.4 2 .5 2 .2 1 .9 2.0 2 .2 Day 48 1 .9 2 .3 2 .1 2 .3 2 .1 2 .3 2 .0 2 .0 1 .9 1 .9 2 .1 1 .9 2 .1 2 .1 2 .0 2 .4 2 .1 2.2 2 .4 2 .2 2 .8 2 .2 2 .5 2 .1 2 .3 2 .2 2 .4 2.4 2 .5 2.2 1 .9 2 .0 2.2 INDIVIDUAL DOSE VOLUMES Day 49 Day 50 Day 51 (mL) Day 52 2 .0 2 .3 2 .2 2 .3 2 .1 2 .3 2 .1 2 .0 2 .0 2 .0 2 .3 1 .9 2 .1 2 .2 2 .1 2.4 2 .3 2 .2 2.4 2 .2 2 .9 2 .2 2 .5 2 .2 2.4 2 .2 2 .5 2 .4 2 .5 2 .0 1 .9 2 .1 2 .2 2 .0 2 .3 2 .2 2 .3 2 .1 2 .3 2 .1 2 .0 2 .0 2 .0 2 .3 1 .9 2 .1 2 .2 2 .1 2 .4 2 .3 2.2 2 .4 2.2 2 .9 2 .2 2 .5 2 .2 2 .4 2.2 2 .5 2 .4 2 .5 2 .0 1 .9 2 .1 2.2 2. 0 2 .3 2. 2 2. 3 2. 1 2. 3 2. 1 2. 0 2. 0 2. 0 2. 3 1. 9 2. 1 2. 2 2. 1 2.4 2. 3 2. 2 2. 4 2. 2 2. 9 2-2 2. 5 2. 2 2.4 2. 2 2. 5 2. 4 2.5 2. 0 1. 9 2. 1 2.2 2 .0 2 .3 2.2 2 .3 2 .1 2 .3 2 .1 2 .0 2 .0 2 .0 2 .3 1 .9 2 .1 2 .2 2 .1 2 .4 2 .3 2 .2 2.4 2 .2 2 .9 2 .2 2 .5 2 .2 2 .4 2 .2 2 .5 2.4 2 .5 2 .0 1 .9 2 .1 2.2 Day 53 2 .0 2 .3 2 .2 2 .3 2 .1 2 .3 2 .1 2 .0 2 .0 2 .0 2 .3 1 .9 2 .1 2 .2 2 .1 2 .4 2 .3 2 .2 2 .4 2 .2 2 .9 2 .2 2 .5 2 .2 2 .4 2 .2 2 .5 2.4 2 .5 2 .0 1 .9 2 .1 2.2 Day 54 2.0 2.3 2.2 2.3 2.1 2.3 2.1 2.0 2.0 2.0 2.3 1.9 2.1 2.2 2.1 2.4 2.3 2.2 2.4 2.2 2.9 2.2 2.5 2.2 2.4 2.2 2.5 2.4 2.5 2.0 1.9 2.1 2.2 546 CompanySanRIzed. Does not con H-24516: Subchronic Toxicity 90-Day Gavage Study in Rats with One-Generation Reproduction Evaluations Day 56 Day 57 Female, IV - 25 ing/kg/day 643390 2.1 2.1 643396 2.4 2.4 643380 2.4 2.4 643433 2.4 2.4 643389 1.8 1.8 643410 2.4 2.4 643321 643324 2.2 2.2 643458 2.1 2.1 643364 2.0 2.0 643483 1.9 1.9 643411 643379 2.2 2.2 643391 2.0 2.0 643437 2.1 2.1 643399 2.2 2.2 643334 2.1 2.1 643464 2.4 2.4 643369 2.3 2.3 643490 2.3 2.3 643342 2.5 2.5 643438 2.2 2.2 643445 2.9 2.9 643418 2.2 2.2 643325 2.7 2.7 643479 2.2 2.2 643403 2.4 2.4 643376 2.3 2.3 643422 2.6 2.6 643452 2.5 2.5 643475 2.4 2.4 643372 2.2 2.2 643400 2.0 2.0 643395 2.1 2.1 643457 2.2 2.2 Day 58 2. 1 2. 4 2. 4 2. 4 1. 8 2. 4 2. 2 2. 1 2. 0 1. 9 2. 2 2. 0 2. 1 2.2 2. 1 2. 4 2. 3 2. 3 2. 5 2. 2 2. 9 2. 2 2. 7 2. 2 2. 4 2. 3 2. 6 2..5 2..4 2,,2 2..0 2.,1 2,.2 INDIVIDUAL DOSE VOLUMES (mL) Day 59 Day 60 Day 61 Day 62 2.1 2.1 2.1 2.1 2.4 2.4 2.4 2.4 2.4 2.4 2.4 2.4 2.4 2.4 2.4 2.4 1.8 1.8 1.8 1.8 2.4 2.4 2.4 2.4 2.2 2.2 2.2 2.2 2.1 2.1 2.1 2.1 2.0 2.0 2.0 2.0 1.9 1.9 1.9 1.9 2.2 2.2 2.2 2.2 2.0 2.0 2.0 2.0 2.1 2.1 2.1 2.1 2.2 2.2 2.2 2.2 2.1 2.1 2.1 2.1 2.4 2.4 2.4 2.4 2.3 2.3 2.3 2.3 2.3 2.3 2.3 2.3 2.5 2.5 2.5 2.5 2.2 2.2 2.2 2.2 2.9 2.9 2.9 2.9 2.2 2.2 2.2 2.2 2.7 2.7 2.7 2.7 2.2 2.2 2.2 2.2 2.4 2.4 2.4 2.4 2.3 2.3 2.3 2.3 2.6 2.6 2.6 2.6 2.5 2.5 2.5 2.5 2.4 2.4 2.4 2.4 2.2 2.2 2.2 2.2 2.0 2.0 2.0 2.0 2.1 2.1 2.1 2.1 2.2 2.2 2.2 2.2 Day 63 2.1 2.5 2.3 2.5 2.2 2.3 2.2 2.1 2.1 2.0 2.3 2.1 2.2 2.2 2.2 2.5 2.3 2.2 2.5 2.3 2.9 2.2 2.7 2.3 2.4 2.3 2.7 2.6 2.5 2.2 2.0 2.2 2.3 Day 64 2.1 2.5 2.3 2.5 2.2 2.3 2.2 2.1 2.1 2.0 2.3 2.1 2.2 2.2 2.2 2.5 2.3 2.2 2.5 2.3 2.9 2.2 2.7 2.3 2.4 2.3 2.7 2.6 2.5 2.2 2.0 2.2 2.3 547 ConqMHiy Sanitized. Does not con H-24516: Subchronic Toxicity 90-Day Gavage Study in Rats with One-Generation Reproduction Evaluations Day 66 Day 67 Female, IV - 25 ing/kg/day 643390 2 .1 2 .1 643396 2 .5 2 .5 643380 2 .3 2 .3 643433 2 .5 2 .5 643389 2 .2 2 .2 643410 2 .3 2 .3 643321 643324 2 .2 2 .2 643458 2 .1 2 .1 643364 2 .1 2 .1 643483 2 .0 2 .0 643411 643379 2 .3 2 .3 643391 2 .1 2 .1 643437 2 .2 2 .2 643399 2 .2 2 .2 643334 2 .2 2 .2 643464 2 .5 2 .5 643369 2 .3 2 .3 643490 2 .2 2 .2 643342 2 .5 2 .5 643438 2 .3 2 .3 643445 2 .9 2 .9 643418 2 .2 2 .2 643325 2 .7 2 .7 643479 2 .3 2 .3 643403 2 .4 2 .4 643376 2 .3 2 .3 643422 2 .7 2 .7 643452 2 .6 2 .6 643475 2 .5 2 .5 643372 2.2 2 .2 643400 2 .0 2 .0 643395 2 .2 2.2 643457 2 .3 2 .3 Day 68 2 .1 2 .5 2 .3 2 .5 2 .2 2 .3 2 .2 2 .1 2 .1 2 .0 2 .3 2 .1 2 .2 2.2 2.2 2 .5 2 .3 2 .2 2 .5 2 .3 2 .9 2 .2 2 .7 2 .3 2.4 2 .3 2 .7 2 .6 2 .5 2 .2 2 .0 2 .2 2 .3 INDIVIDUAL DOSE VOLUMES (mL) Day 69 Day 70 Day 71 Day 72 2 .1 2 .5 2 .3 2 .5 2 .2 2 .3 2.2 2 .1 2 .1 2 .0 2 .3 2 .1 2 .2 2 .2 2 .2 2 .5 2.3 2 .2 2 .5 2 .3 2 .9 2.2 2 .7 2 .3 2 .4 2 .3 2 .7 2 .6 2 .5 2 .2 2 .0 2 .2 2 .3 2 .1 2 .6 2 .4 2 .6 2 .3 2.4 2 .2 2 .2 2 .1 2 .0 2 .3 2 .1 2 .3 2 .3 2 .2 2 .5 2 .4 2 .3 2 .5 2 .4 3 .0 2 .3 2 .7 2.2 2 .4 2 .3 2 .7 2 .6 2 .5 2 .3 2 .0 2 .2 2 .3 2 .1 2 .6 2 .4 2 .6 2 .3 2 .4 2 .2 2 .2 2 .1 2 .0 2 .3 2 .1 2 .3 2 .3 2 .2 2 .5 2 .4 2 .3 2 .5 2 .4 3 .0 2 .3 2 .7 2 .2 2 .4 2 .3 2 .7 2 .6 2 .5 2 .3 2 .0 2 .2 2 .3 2 .1 2 .6 2 .4 2 .6 2 .3 2.4 2 .2 2 .2 2 .1 2 .0 2 .3 2 .1 2 .3 2 .3 2.2 2.5 2.4 2 .3 2 .5 2 .4 3 .0 2 .3 2 .7 2 .2 2 .4 2 .3 2 .7 2 .6 2 .5 2 .3 2 .0 2 .2 2 .3 Day 73 2 .1 2 .6 2 .4 2 .6 2.3 2.4 2.2 2 .2 2 .1 2 .0 2 .3 2 .1 2 .3 2 .3 2 .2 2 .5 2 .4 2 .3 2 .5 2.4 3 .0 2 .3 2 .7 2 .2 2 .4 2 .3 2 .7 2 .6 2 .5 2 .3 2 .0 2 .2 2 .3 Day 74 2.1 2.6 2.4 2.6 2.3 2.4 2.2 2.2 2.1 2.0 2.3 2.1 2.3 2.3 2.2 2.5 2.4 2.3 2.5 2.4 3.0 2.3 2.7 2.2 2.4 2.3 2.7 2.6 2.5 2.3 2.0 2.2 2.3 548 Company Sanitized. Does not conta H-24516: Subchronic Toxicity 90-Day Gavage Study in Rats with One-Generation Reproduction Evaluations Day 76 Day 77 Female, IV - 25 mg/kg/day 643390 2.1 2.2 643396 2.6 2.7 643380 2.4 2.4 643433 2.6 2.6 643389 2.3 2.2 643410 2.4 2.4 643321 643324 2.2 2.2 643458 2.2 2.3 643364 2.1 2.2 643483 2.0 2.0 643411 643379 2.3 2.3 643391 2.1 2.1 643437 2.3 2.2 643399 643334 643464 643369 643490 643342 643438 643445 643418 643325 643479 643403 643376 643422 643452 643475 643372 643400 643395 643457 Day 78 2.2 2.7 2.4 2.6 2.2 2.4 2.2 2.3 2.2 2.0 2.3 2.1 2.2 INDIVIDUAL DOSE VOLUMES (mL) Day 79 Day 80 Day 81 Day 82 2.2 2.2 2.2 2.2 2.7 2.7 2.7 2.7 2.4 2.4 2.4 2.4 2.6 2.6 2.6 2.6 2.2 2.2 2.2 2.2 2.4 2.4 2.4 2.4 2.2 2.2 2.2 2.2 2.3 2.3 2.3 2.3 2.2 2.2 2.2 2.2 2.0 2.0 2.0 2.0 2.3 2.3 2.3 2.3 2.1 2.1 2.1 2.1 2.2 2.2 2.2 2.2 Day 83 2.2 2.7 2.4 2.6 2.2 2.4 2.2 2.3 2.2 2.0 2.3 2.1 2.2 Day 84 2.2 2.7 2.5 2.6 2.2 2.4 2.3 2.2 2.2 2.0 2.3 2.1 2.3 549 Company Sanitized. Does not conta H-24516: Subchronic Toxicity 90-Day Gavage Study in Rats with One-Generation Reproduction Evaluations Day 86 Day 87 Female, IV - 25 mg/kg/day 643390 2.2 2.2 643396 2.7 2.7 643380 2.5 2.5 643433 2.6 2.6 643389 2.2 2.2 643410 2.4 2.4 643321 643324 2.3 2.3 643458 2.2 2.2 643364 2.2 2.2 643483 2.0 2.0 643411 643379 2.3 2.3 643391 2.1 2.1 643437 2.3 2.3 643399 643334 643464 643369 643490 643342 643438 643445 643418 643325 643479 643403 643376 643422 643452 643475 643372 643400 643395 643457 Day 88 2.2 2.7 2.5 2.6 2.2 2.4 2.3 2.2 2.2 2.0 2.3 2.1 0.3 INDIVIDUAL DOSE VOLUMES (mL) Day 89 Day 90 Day 91 Day 92 2.2 2.2 2.2 2.2 2.7 2.7 2.7 2.7 2.5 2.5 2.5 2.5 2.6 2.6 2.7 2.7 2.2 2.2 2.2 2.2 2.4 2.4 2.4 2.4 2.3 2.3 2.3 2.3 2.2 2.2 2.3 2.3 2.2 2.2 2.2 2.2 2.0 2.3 2.1 2.3 550 Company Sanitized. Does not conta H-24516: Subchronic Toxicity 90-Day Gavage Study in Rats with One-Generation Reproduction Evaluations INDIV311)UAL DOE;ii VOLUME!i (mL) Day 0 Day 1 Day 2 Day 3 Day 4 Day 5 Day 6 Day 7 Day 8 Day 9 Day Female, VI - 100 mg/kg/day 643322 1.9 1.9 1.9 1.9 1.9 1.9 1.9 2.1 2.1 2.1 643489 1.8 1.8 1.8 1.8 1.8 1.8 1.8 2.0 2.0 2.0 643409 1.7 1.7 1.7 1.7 1.7 1.7 1.7 2.0 2.0 2.0 643366 1.7 1.7 1.7 1.7 1.7 1.7 1.7 2.0 2.0 2.0 643367 1.9 1.9 1.9 1.9 1.9 1.9 1.9 2.2 2.2 2.2 643461 2.1 2.1 2.1 2.1 2.1 2.1 2.1 2.6 2.6 2.6 643462 2.0 2.0 2.0 2.0 2.0 2.0 2.0 2.3 2.3 2.3 643392 1.6 1.6 1.6 1.6 1.6 1.6 1.6 1.8 1.8 1.8 643472 1.7 1.7 1.7 1.7 1.7 1.7 1.7 2.0 2.0 2.0 643323 1.7 1.7 1.7 1.7 1.7 1.7 1.7 1.9 1.9 1.9 643412 1.8 1.8 1.8 1.8 1.8 1.8 1.8 2.1 2.1 2.1 643382 1.8 1.8 1.8 1.8 1.8 1.8 1.8 2.0 2.0 2.0 643381 1.8 1.8 1.8 1.8 1.8 1.8 1.8 2.1 2.1 2.1 643360 1.6 1.6 1.6 1.6 1.6 1.6 1.6 1.8 1.8 1.8 643373 1.9 1.9 1.9 1.9 1.9 1.9 1.9 2.3 2.3 2.3 643320 1.8 1.8 1.8 1.8 1.8 1.8 1.8 2.1 2.1 2.1 643488 1.8 1.8 1.8 1.8 1.8 1.8 1.8 2.1 2.1 2.1 643428 2.2 2.2 2.2 2.2 2.2 2.2 2.2 2.4 2.4 2.4 643439 1.9 1.9 1.9 1.9 1.9 1.9 1.9 2.2 2.2 2.2 643353 1.9 1.9 1.9 1.9 1.9 1.9 1.9 2.2 2.2 2.2 643385 2.0 2.0 2.0 2.0 2.0 2.0 2.0 2.2 2.2 2.2 643339 1.8 1.8 1.8 1.8 1.8 1.8 1.8 2.1 2.1 2.1 643473 1.8 1.8 1.8 1.8 1.8 1.8 1.8 2.0 2.0 2.0 643337 2.1 2.1 2.1 2.1 2.1 2.1 2.1 2.4 2.4 2.4 643416 1.8 1.8 1.8 1.8 1.8 1.8 1.8 2.1 2.1 2.1 643407 2.1 2.1 2.1 2.1 2.1 2.1 2.1 2.2 2.2 2.2 643357 1.7 1.7 1.7 1.7 1.7 1.7 1.7 2.0 2.0 2.0 643331 1.9 1.9 1.9 1.9 1.9 1.9 1.9 2.1 2.1 2.1 643427 1.9 1.9 1.9 1.9 1.9 1.9 1.9 2.1 2.1 2.1 643470 1.9 1.9 1.9 1.9 1.9 1.9 1.9 2.0 2.0 2.0 643434 2.0 2.0 2.0 2.0 2.0 2.0 2.0 2.2 2.2 2.2 643349 2.0 2.0 2.0 2.0 2.0 2.0 2.0 2.2 2.2 2.2 643454 2.0 2.0 2.0 2.0 2.0 2.0 2.0 2.2 2.2 2.2 643333 1.8 1.8 1.8 1.8 1.8 1.8 1.8 2.1 2.1 2.1 643460 1.9 1.9 1.9 1.9 1.9 1.9 1.9 2.2 2.2 2.2 551 Company Sanitized. Does not H-24516: Subchronic Toxicity 90-Day Gavage Study in Rats with One-Generation Reproduction Evaluations INDIVI:E)UAL DOS1E! VOLUME;; (mL) Day 12 Day 13 Day 14 Day 15 Day 16 Day 17 Day 18 Day 19 Day 20 Day 21 Day Female, VI - 100 nig/kg/day 643322 2.1 2.1 2.3 2.3 2.3 2.3 2.3 2.3 2.3 2.5 643489 2.0 2.0 2.2 2.2 2.2 2.2 2.2 2.2 2.2 2.4 643409 2.0 2.0 2.2 2.2 2.2 2.2 2.2 2.2 2.2 2.3 643366 2.0 2.0 2.1 2.1 2.1 2.1 2.1 2.1 2.1 2.3 643367 2.2 2.2 2.3 2.3 2.3 2.3 2.3 2.3 2.3 2.6 643461 2.6 2.6 2.8 2.8 2.8 2.8 2.8 2.8 2.8 2.9 643462 2.3 2.3 2.5 2.5 2.5 2.5 2.5 2.5 2.5 2.7 643392 1.8 1.8 2.0 2.0 2.0 2.0 2.0 2.0 2.0 2.1 643472 2.0 2.0 2.1 2.1 2.1 2.1 2.1 2.1 2.1 2.2 643323 1.9 1.9 2.1 2.1 2.1 2.1 2.1 2.1 2.1 2.3 643412 2.1 2.1 2.3 2.3 2.3 2.3 2.3 2.3 2.3 2.5 643382 2.0 2.0 2.1 2.1 2.1 2.1 2.1 2.1 2.1 2.3 643381 2.1 2.1 2.2 2.2 2.2 2.2 2.2 2.2 2.2 2.4 643360 1.8 1.8 2.0 2.0 2.0 2.0 2.0 2.0 2.0 2.2 643373 2.3 2.3 2.4 2.4 2.4 2.4 2.4 2.4 2.4 2.7 643320 2.1 2.1 2.3 2.3 2.3 2.3 2.3 2.3 2.3 2.5 643488 2.1 2.1 2.2 2.2 2.2 2.2 2.2 2.2 2.2 2.4 643428 2.4 2.4 2.8 2.8 2.8 2.8 2.8 2.8 2.8 2.8 643439 2.2 2.2 2.4 2.4 2.4 2.4 2.4 2.4 2.4 2.5 643353 2.2 2.2 2.3 2.3 2.3 2.3 2.3 2.3 2.3 2.4 643385 2.2 2.2 2.5 2.5 2.5 2.5 2.5 2.5 2.5 2.7 643339 2.1 - 2.1 2.3 2.3 2.3 2.3 2.3 2,3 2.3 2.3 643473 2.0 2.0 2.2 2.2 2.2 2.2 2.2 2.2 2.2 2.3 643337 2.4 2.4 2.6 2.6 2.6 2.6 2.6 2.6 2.6 2.9 643416 2.1 2.1 2.3 2.3 2.3 2.3 2.3 2.3 2.3 2.4 643407 2.2 2.2 2.5 2.5 2.5 2.5 2.5 2.5 2.5 2.7 643357 2.0 2.0 2.1 2.1 2.1 2.1 2.1 2.1 2.1 2.2 643331 2.1 2.1 2.3 2.3 2.3 2.3 2.3 2.3 2.3 2.4 643427 2.1 2.1 2.3 2.3 2.3 2.3 2.3 2.3 2.3 2.5 643470 2.0 2.0 2.3 2.3 2.3 2.3 2.3 2.3 2.3 2.4 643434 2.2 2.2 2.3 2.3 2.3 2.3 2.3 2.3 2.3 2.5 643349 2.2 2.2 2.5 2.5 2.5 2.5 2.5 2.5 2.5 2.6 643454 2.2 2.2 2.4 2.4 2.4 2.4 2.4 2.4 2.4 2.5 643333 2.1 2.1 2.3 2.3 2.3 2.3 2.3 2.3 2.3 2.4 643460 2.2 2.2 2.5 2.5 2.5 2.5 2.5 2.5 2.5 2.6 552 Company Sanitized. Does not 'eg- H-24516: Subchronic Toxicity 90-Day Gavage Study in Rats with One-Generation Reproduction Evaluations INDIVIDUAL DOSE VOLUMES (mL) Day 24 Day 25 Day 26 Day 27 Day 28 Day 29 Day 30 Day 31 Day 32 Day 33 Day Female, VI - 100 mg/kg/day 643322 2 .5 2.5 2. 5 2 .5 2 .6 2.6 2 .6 2.6 2.6 2.6 643489 2.4 2.4 2.4 2.4 2 .4 2.4 2 .4 2.4 2.4 2.4 643409 2 .3 2.3 2. 3 2 .3 2 .5 2.5 2 .5 2.5 2.5 2.5 643366 2 .3 2.3 2. 3 2 .3 2 .5 2.5 2 .5 2.5 2.5 2.5 643367 2 .6 2.6 2. 6 2 .6 2 .7 2.7 2 .7 2.7 2.7 2.7 643461 2 .9 2.9 2. 9 2 .9 3 .0 3.0 3 .0 3.0 3.0 3.0 643462 2 .7 2.7 2. 7 2 .7 2 .8 2.8 2 .8 2.8 2.8 2.8 643392 2 .1 2.1 2. 1 2 .1 2 .2 2.2 2 .2 2.2 2.2 2.2 643472 2 .2 2.2 2. 2 2 .2 2 .3 2.3 2 .3 2.3 2.3 2.3 643323 2 .3 2.3 2. 3 2 .3 2 .4 2.4 2 .4 2.4 2.4 2.4 643412 2 .5 2.5 2. 5 2 .5 2 .5 2.5 2 .5 2.5 2.5 2.5 643382 2 .3 2.3 2. 3 2 .3 2 .0 2.0 2 .0 2.0 2.0 2.0 643381 2.4 2.4 2. 4 2 .4 2 .4 2.4 2 .4 2.4 2.4 2.4 643360 2 .2 2.2 2. 2 2 .2 2 .3 2.3 2 .3 2.3 2.3 2.3 643373 2 .7 2.7 2. 7 2 .7 2 .8 2.8 2 .8 2.8 2.8 2.8 643320 2 .5 2.5 2. 5 2 .5 2 .6 2.6 2 .6 2.6 2.6 2.6 643488 2.4 2.4 2. 4 2.4 2 .6 2.6 2 .6 2.6 2.6 2.6 643428 2 .8 2.8 2. 8 2 .8 3 .0 3.0 3 .0 3.0 3.0 3.0 643439 2 .5 2.5 2. 5 2 .5 2 .6 2.6 2 .6 2.6 2.6 2.6 643353 2 .4 2.4 2. 4 2 .4 2 .6 2.6 2 .6 2.6 2.6 2.6 643385 2 .7 2.7 2. 7 2 .7 2 .8 2.8 2 .8 2.8 2.8 2.8 643339 2 .3 2.3 2. 3 2 .3 2 .6 2.6 2 .6 2.6 2.6 2.6 643473 2 .3 2.3 2. 3 2 .3 2 .4 2.4 2 .4 2.4 2.4 2.4 643337 2 .9 2.9 2. 9 2 .9 3 .1 3.1 3 .1 3.1 3.1 3.1 643416 2 .4 2.4 2.4 2 .4 2 .6 2.6 2 .6 2.6 2.6 2.6 643407 2 .7 2.7 2. 7 2 .7 2 .9 2.9 2 .9 2.9 2.9 2.9 643357 2 .2 2.2 2. 2 2 .2 2 .5 2.5 2 .5 2.5 2.5 2.5 643331 2 .4 2.4 2. 4 2.4 2 .6 2.6 2 .6 2.6 2.6 2.6 643427 2 .5 2.5 2, 5 2 .5 2 .5 2.5 2 .5 2.5 2.5 2.5 643470 2.4 2.4 2.4 2 .4 2 .6 2.6 2 .6 2.6 2.6 2.6 643434 2 .5 2.5 2. 5 2 .5 2 .6 2.6 2 .6 2.6 2.6 2.6 643349 2 .6 2.6 2. 6 2 .6 2 .8 2.8 2 .8 2.8 2.8 2.8 643454 2 .5 2.5 2. 5 2 .5 2 .6 2.6 2 .6 2.6 2.6 2.6 643333 2 .4 2.4 2. 4 2 .4 2 .4 2.4 2.4 2.4 2.4 2.4 643460 2 .6 2.6 2.6 2 .6 2 .8 2.8 2 .8 2.8 2.8 2.8 553 Company Sanitized. Does no H-24516: Subchronic Toxicity 90-Day Gavage Study in Rats with One-Generation Reproduction Evaluations Day 36 Day 37 Female, VI - 100 ing/kg/day 643322 643489 643409 643366 643367 643461 643462 643392 643472 643323 643412 643382 643381 643360 643373 643320 643488 643428 643439 643353 643385 643339 643473 643337 643416 643407 643357 643331 643427 643470 643434 643349 643454 643333 643460 2 .7 2 .6 2 .6 2 .6 2 .8 3 .2 2 .9 2 .4 2 .4 2 .5 2 .6 2 .0 2 .5 2 .2 2 .8 2 .8 2 .6 3 .1 2 .8 2 .7 2 .9 2 .7 2 .5 2 .8 2.6 3 .0 2 .5 2 .7 2 .7 2 .7 2.7 2 .9 2 .8 2 .6 2 .9 2 .7 2 .6 2 .6 2 .6 2 .8 3 .2 2 .9 2 .4 2 .4 2 .5 2 .6 2 .0 2 .5 2 .2 2 .8 2 .8 2 .6 3 .1 2 .8 2 .7 2 .9 - 2 .7 2 .5 2 .8 2 .6 3 .0 2.5 2 .7 2 .7 2 .7 2 .7 2 .9 2 .8 2 .6 2.9 Day 38 2 .0 2 .0 2 .0 2 .0 2 .1 2.4 2 .2 1 .8 1 .8 1 .9 1 .9 1 .5 1 .9 1 .7 2 .1 2 .1 2 .0 2 .3 2 .1 2 .1 2 .2 2 .0 1 .9 2 .1 2 .0 2 .2 1 .9 2 .0 2 .0 2 .0 2 .1 2 .2 2 .1 2 .0 2.2 Day 39 INDIVIDUAL DOSE VOLUMES (mL) Day 40 Day 41 Day 42 2 .0 2 .0 2 .0 2 .0 2 .1 2.4 2 .2 1 .8 1 .8 1 .9 1 .9 1 .5 1 .9 1 .7 2 .1 2 .1 2 .0 2 .3 2 .1 2 .1 2 .2 2 .0 1 .9 2 .1 2 .0 2.2 1 .9 2 .0 2 .0 2 .0 2 .1 2.2 2 .1 2 .0 2 .2 2 .0 2 .0 2 .0 2 .0 2 .1 2 .4 2 .2 1 .8 1 .8 1 .9 1 .9 1 .5 1 .9 1 .7 2 .1 2 .1 2 .0 2 .3 2 .1 2 .1 2 .2 2.0 1 .9 2 .1 2 .0 2 .2 1 .9 2 .0 2 .0 2 .0 2 .1 2 .2 2 .1 2 .0 2 .2 2 .0 2 .0 2 .0 2 .0 2 .1 2 .4 2 .2 1 .8 1 .8 1 .9 1 .9 1 .5 1 .9 1 .7 2 .1 2 .1 2 .0 2 .3 2 .1 2 .1 2 .2 2 .0 1 .9 2 .1 2 .0 2 .2 1 .9 2 .0 2 .0 2 .0 2 .1 2 .2 2 .1 2 .0 2.2 2 .1 2 .0 2 .0 2 .1 2 .1 2 .5 2 .2 1 .9 1 .9 2 .0 2 .0 1 .4 2 .0 1 .9 2 .3 2.2 2 .1 2 .4 2 .1 2 .1 2 .2 2 .1 2 .0 2 .1 2 .0 2 .3 2 .0 2 .1 2 .1 2 .1 2 .1 2 .3 2 .2 2 .0 2 .3 Day 43 2 .1 2 .0 2 .0 2 .1 2 .1 2 .5 2 .2 1 .9 1 .9 2 .0 2 .0 1 .4 2 .0 1 .9 2 .3 2 .2 2 .1 2 .4 2 .1 2 .1 2 .2 2 .1 2 .0 2 .1 2 .0 2 .3 2 .0 2 .1 2 .1 2 .1 2 .1 2 .3 2 .2 2 .0 2.3 Day 44 2 .1 2 .0 2 .0 2 .1 2 .1 2 .5 2.2 1 .9 1 .9 2 .0 2 .0 1 .4 2 .0 1 .9 2 .3 2 .2 2 .1 2 .4 2.1 2 .1 2.2 2 .1 2 .0 2 .1 2 .0 2 .3 2 .0 2 .1 2 .1 2 .1 2 .1 2 .3 2 .2 2 .0 2.3 554 Pwnpany Sanitized. Does not co H-24516: Subchronic Toxicity 90-Day Gavage Study in Rats with One-Generation Reproduction Evaluations Day 46 Day 47 Female, VI - 100 ing/kg/day 643322 2 .1 2 .1 643489 2 .0 2 .0 643409 2 .0 2 .0 643366 2 .1 2 .1 643367 2 .1 2 .1 643461 2 .5 2 .5 643462 2 .2 2 .2 643392 1 .9 1 .9 643472 1 .9 1 .9 643323 2 .0 2 .0 643412 2 .0 2 .0 643382 1 .4 1 .4 643381 2 .0 2 .0 643360 1 .9 1 .9 643373 2 .3 2 .3 643320 2 .2 2 .2 643488 2 .1 2 .1 643428 2 .4 2 .4 643439 2 .1 2 .1 643353 2 .1 2 .1 643385 2.2 2 .2 643339 2 .1 2 .1 643473 2 .0 2 .0 643337 2 .1 2 .1 643416 2 .0 2 .0 643407 2 .3 2 .3 643357 2 .0 2 .0 643331 2 .1 2 .1 643427 2 .1 2 .1 643470 2 .1 2 .1 643434 2 .1 2 .1 643349 2 .3 2 .3 643454 2 .2 2 .2 643333 2 .0 2 .0 643460 2 .3 2 .3 Day 48 2 .1 2 .0 2 .0 2 .1 2 .1 2 .5 2 .2 1 .9 1 .9 2 .0 2 .0 1 .4 2 .0 1 .9 2 .3 2 .2 2 .1 2.4 2 .1 2 .1 2 .2 2 .1 2 .0 2 .1 2 .0 2 .3 2 .0 2 .1 2 .1 2 .1 2 .1 2 .3 2.2 2.0 2 .3 INDIVIDUAL DOSE VOLUMES (mL) Day 49 Day 50 Day 51 Day 52 2 .1 2.1 2 .1 2 .1 2 .1 2.1 2 .1 2 .1 2 .0 2.0 2 .0 2 .0 2 .1 2.1 2 .1 2 .1 2 .2 2.2 2 .2 2 .2 2 .4 2.4 2 .4 2 .4 2.2 2.2 2 .2 2 .2 1 .9 1.9 1 .9 1 .9 1 .9 1.9 1 .9 1 .9 1 .9 1.9 1 .9 1 .9 2 .0 2.0 2 .0 2 .0 1 .7 1.7 1 .7 1 .7 2 .0 2.0 2 .0 2 .0 1 .9 1.9 1 .9 1 .9 2 .3 2.3 2 .3 2 .3 2 .2 2.2 2.2 2 .2 2 .1 2.1 2 .1 2 .1 2 .4 2.4 2.4 2 .4 2 .2 2.2 2 .2 2.2 2 .3 2.3 2 .3 2 .3 2 .3 2.3 2 .3 2 .3 2 .2 2.2 2 .2 2 .2 2 .0 2.0 2 .0 2 .0 2 .3 2.3 2 .3 2 .3 2 .1 2.1 2 .1 2 .1 2 .4 2.4 2 .4 2.4 2 .1 2.1 2 .1 2 .1 2 .2 2.2 2 .2 2 .2 2 .1 2.1 2 .1 2 .1 2 .2 2.2 2 .2 2 .2 2 .2 2.2 2 .2 2 .2 2 .3 2.3 2 .3 2 .3 2 .3 2.3 2 .3 2 .3 2 .1 2.1 2 .1 2 .1 2 .3 2.3 2 .3 2;.3 Day 53 2 .1 2 .1 2 .0 2 .1 2 .2 2 .4 2.2 1 .9 1 .9 1 .9 2.0 1 .7 2 .0 1 .9 2 .3 2 .2 2 .1 2 .4 2 .2 2 .3 2 .3 2 ,2 2 .0 2 .3 2 .1 2 .4 2 .1 2.2 2 .1 2 .2 2 .2 2 .3 2 .3 2 .1 2 !.3 Day 54 2 . 2 . 2 . 2 . 2. 2 . 2 . 1 . 1 . 1 . 2 . 1 . 2 . 1 . 2 . 2 . 2 . 2. 2 . 2 . 2 . 2. 2 . 2 . 2 . 2. 2 . 2 . 2 . 2 2 . 2 2 2 2 555 Company Sanitized. Does not con H-24516: Subchronic Toxicity 90-Day Gavage Study in Rats with One-Generation Reproduction Evaluations Day 56 Day 57 Female, VI - 100 mg/kg/day 643322 2. 1 2.1 643489 2. 2 2.2 643409 2. 0 2.0 643366 2. 1 2.1 643367 2. 2 2.2 643461 2. 4 2.4 643462 2. 3 2.3 643392 1. 9 1.9 643472 1. 9 1.9 643323 2. 0 2.0 643412 2. 1 2.1 643382 1. 7 1.7 643381 2. 0 2.0 643360 1. 9 1.9 643373 2. 2 2.2 643320 2. 3 2.3 643488 2. 1 2.1 643428 2. 3 2.3 643439 2. 2 2.2 643353 2. 3 2.3 643385 2. 3 2.3 643339 2. 2 2.2 643473 2. 1 2.1 643337 2. 3 2.3 643416 2. 1 2.1 643407 2. 4 2.4 643357 2. 1 2.1 643331 2. 3 2.3 643427 2. 2 2.2 643470 2. 2 2.2 643434 2. 2 2.2 643349 2. 4 2.4 643454 2, 3 2.3 643333 2. 0 2.0 643460 2. 3 2.3 Day 58 2.1 2.2 2.0 2.1 2.2 2.4 2.3 1.9 1.9 2.0 2.1 1.7 2.0 1.9 2.2 2.3 2.1 2.3 2.2 2.3 2.3 2.2 2.1 2.3 2.1 2.4 2.1 2.3 2.2 2.2 2.2 2.4 2.3 2.0 2.3 INDI\riDUAL DOS;E VOL,UMES Day 59 Day 60 Day 61 (mL) Day 62 2.1 2.1 2.1 2.1 2.2 2.2 2.2 2.2 2.0 2.0 2.0 2.0 2.1 2.1 2.1 2.1 2.2 2.2 2.2 2.2 2.4 2.4 2.4 2.4 2.3 2.3 2.3 2.3 1.9 1.9 1.9 1.9 1.9 1.9 1.9 1.9 2.0 2.0 2.0 2.0 2.1 2.1 2.1 2.1 1.7 1.7 1.7 1.7 2.0 2.0 2.0 2.0 1.9 1.9 1.9 1.9 2.2 2.2 2.2 2.2 2.3 2.3 2.3 2.3 2.1 2.1 2.1 2.1 2.3 2.3 2.3 2.3 2.2 2.2 2.2 2.2 2.3 2.3 2.3 2.3 2.3 2.3 2.3 2.3 2.2 2.2 2.2 2.2 2.1 2.1 2.1 2.1 2.3 2.3 2.3 2.3 2.1 2.1 2.1 2.1 2.4 2.4 2.4 2.4 2.1 2.1 2.1 2.1 2.3 2.3 2.3 2.3 2.2 2.2 2.2 2.2 2.2 2.2 2.2 2.2 2.2 2.2 2.2 2.2 2.4 2.4 2.4 2.4 2.3 2.3 2.3 2.3 2.0 2.0 2.0 2.0 2.3 2.3 2.3 2.3 Day 63 2.2 2.2 2.0 2.2 2.2 2.5 2.3 2.0 2.0 2.1 2.1 1.8 2.1 1.9 2.3 2.3 2.2 2.4 2.2 2.3 2.3 2.2 2.0 2.4 2.1 2.5 2.1 2.3 2.1 2.3 2.1 2.4 2.3 2.1 2.4 Day 64 2.2 2.2 2.0 2.2 2.2 2.5 2.3 2.0 2.0 2.1 2.1 1.8 2.1 1.9 2.3 2.3 2.2 2.4 2.2 2.3 2.3 2.2 2.0 2.4 2. 2. 2. 2. 2. 2. 2. 2. 2. 2. 2. 556 Company Sanitized. Does not con H-24516: Subchronic Toxicity 90-Day Gavage Study in Rats with One-Generation Reproduction Evaluations Day 66 Day 67 Female, VI - 100 nig/kg/day 643322 2. 2 643489 2. 2 643409 2. 0 643366 2. 2 643367 2. 2 643461 2. 5 643462 2. 3 643392 2. 0 643472 2. 0 643323 2. 1 643412 2. 1 643382 1. 8 643381 2. 1 643360 1. 9 643373 2.3 643320 2. 3 643488 2. 2 643428 2. 4 643439 2. 2 643353 2. 3 643385 2. 3 643339 2. 2 643473 2. 0 643337 2. 4 643416 2. 1 643407 2. 5 643357 2. 1 643331 2. 3 643427 2. 1 643470 2. 3 643434 2. 1 643349 2. 4 643454 2. 3 643333 2. 1 643460 2..4 2 .2 2 .2 2 .0 2 .2 2 .2 2 .5 2 .3 2 .0 2 .0 2 .1 2 .1 1 .8 2 .1 1 -9 2 .3 2 .3 2 .2 2 .4 2 .2 2 .3 2 .3 2 .2 2 .0 2 .4 2 .1 2 .5 2 .1 2 .3 2 .1 2 .3 2 .1 2 .4 2 .3 2 .1 2 .4 Day 68 2.2 2.2 2.0 2.2 2.2 2.5 2.3 2.0 2.0 2.1 2.1 1.8 2.1 1.9 2.3 2.3 2.2 2.4 2.2 2.3 2.3 2.2 2.0 2.4 2.1 2.5 2.1 2.3 2.1 2.3 2.1 2.4 2.3 2.1 2.4 INDIVIDUAL DOSE VOLUMES Day 69 Day 70 Day 71 (mL) Day 72 2. 2 2.2 2 .2 2.2 2. 2 2.3 2 .3 2.3 2. 0 2.0 2 .0 2.0 2. 2 2.3 2 .3 2.3 2.2 2.3 2 .3 2.3 2. 5 2.4 2 .4 2.4 2. 3 2.4 2 .4 2.4 2. 0 2.1 2 .1 2.1 2.0 2,0 2 .0 2.0 2. 1 2.2 2 .2 2.2 2. 1 2.2 2 .2 2.2 1. 8 1.9 1 .9 1.9 2. 1 2.1 2 .1 2.1 1. 9 2.0 2 .0 2.0 2. 3 2.3 2 .3 2.3 2. 3 2.4 2.4 2.4 2. 2 2.2 2 .2 2.2 2.4 2.4 2 .4 2.4 2. 2 2.2 2 .2 2.2 2. 3 2.4 2.4 2.4 2. 3 2.4 2 .4 2.4 2. 2 2.3 2 .3 2.3 2. 0 2.1 2 .1 2.1 2. 4 2.5 2 .S 2.5 2. 1 2.1 2 .1 2.1 2. 5 2.4 2 .4 2.4 2. 1 2.2 2.2 2.2 2. 3 2.4 2 .4 2.4 2. 1 2.2 2 .2 2.2 2. 3 2.3 2 .3 2.3 2. 1 2.1 2 .1 2.1 2. 4 2.4 2 .4 2.4 2. 3 2.4 2 .4 2.4 2. 1 2.1 2 .1 2.1 2..4 2.4 2 .4 2.4 Day 73 2.2 2.3 2.0 2.3 2.3 2.4 2.4 2.1 2.0 2.2 2.2 1.9 2.1 2.0 2.3 2.4 2.2 2.4 2.2 2.4 2.4 2.3 2.1 2.5 2.1 2.4 2.2 2.4 2.2 2.3 2.1 2.4 2.4 2.1 2.4 Day 74 2.2 2.3 2.0 2.3 2.3 2.4 2.4 2.1 2.0 2.2 2.2 1.9 2.1 2.0 2.3 2.4 2.2 2.4 2.2 2.4 2.4 2.3 2.1 2.5 2.1 2.4 2.2 2.4 2.2 2.3 2.1 2.4 2.4 2.1 2.4 557 Company Sanitized. Does not con H-24516: Subchronic Toxicity 90-Day Gavage Study in Rats with One-Generation Reproduction Evaluations Day 76 Day 77 Female, VI 100 ing/kg/day 643322 2.2 2.2 643489 2.3 2.4 643409 2.0 2.1 643366 2.3 2.3 643367 2.3 2.3 643461 2.4 2.4 643462 2.4 2.4 643392 2.1 2.1 643472 2.0 2.0 643323 2.2 2.2 643412 2.2 2.2 6433B2 1.9 1.9 643381 2.1 2.1 643360 2.0 2.0 643373 2.3 2.4 643320 643488 643428 643439 643353 643385 643339 643473 643337 643416 643407 643357 643331 643427 643470 643434 643349 643454 643333 643460 Day 78 2.2 2.4 2.1 2.3 2.3 2.4 2.4 2.1 2.0 2.2 2.2 1.9 2.1 2.0 2.4 INDIVIDUAL DOSE VOLUMES (mL) Day 79 Day 80 Day 81 Day 82 2.2 2.2 2.2 2 .2 2.4 2.4 2.4 2 .4 2.1 2.1 2.1 2 .1 2.3 2.3 2.3 2 -3 2.3 2.3 2.3 2 .3 2.4 2.4 2.4 2 .4 2.4 2.4 2.4 2 .4 2.1 2.1 2.1 2 .1 2.0 2.0 2.0 2 .0 2.2 2.2 2.2 2.2 2.0 2.2 2.2 2 .2 1.9 1.9 1.9 1 .9 2.1 2.1 2.1 2 .1 2.0 2.0 2.0 2 .0 2.4 2.4 2.4 2.4 Day 83 2 .2 2 .4 2 .1 2 .3 2 .3 2 .4 2 .4 2 .1 2 .0 2.2 2 .2 1 .9 2 .1 2 .0 2.4 Day 84 2 2. 2 2 2 2 2 2 2 2 2 1 2 2 2 558 Company Sanitized. Does not con H-24516: Subchronic Toxicity 90-Day Gavage Study in Rats with One-Generation Reproduction Evaluations Day 86 Day 87 Female, VI 100 ing/kg/day 643322 2.2 2.2 643489 2.4 2.4 643409 2.1 2.1 643366 2.3 2.3 643367 2.3 2.3 643461 2.4 2.4 643462 2.4 2.4 643392 2.0 2.0 643472 2.0 2.0 643323 2.2 2.2 643412 2.3 2.3 643382 1.9 1.9 643381 2.2 2.2 643360 2.0 2.0 643373 2.3 2.3 643320 643488 643428 643439 643353 643385 643339 643473 643337 643416 643407 643357 643331 643427 643470 643434 643349 643454 643333 643460 Day 88 2.2 2.4 2.1 2.3 2.3 2.4 2.4 2.0 2.0 2.2 2.3 1.9 2.2 2.0 2.3 INDIVIDUAL DOSE VOLUMES (mL) Day 89 Day 90 Day 91 Day 92 2.2 2.2 2.2 2.2 2.4 2.4 2.4 2.4 2.1 2.1 2.1 2.1 2.3 2.3 2.3 2.3 2.3 2.3 2.4 2.4 2.4 2.4 2.5 2.5 2.4 2.4 2.4 2.4 2.0 2.0 2.1 2.1 2.0 2.0 2.0 2.0 2.2 2.2 2.1 2.1 2.3 1.9 2.2 2.0 2.3 559 Company Sanitized. Does not co H-24516: Subchronic Toxicity 90-Day Gavage Study in Rats with One-Generation Reproduction Evaluations INDIVI:r)UAL DOS!Ei VOLUME;i (mL) Day 0 Day 1 Day 2 Day 3 Day 4 Day 5 Day 6 Day 7 Day 8 Day 9 Day Female, VIII - 250 nig/kg/day 643341 1.9 1.9 1.9 1.9 1.9 1.9 1.9 2.1 2.1 2.1 643370 2.0 2.0 2.0 2.0 2.0 2-0 2.0 2.4 2.4 2.4 643446 2.0 2.0 2.0 2.0 2.0 2.0 2.0 2.2 2.2 2.2 643435 1.8 1.8 1.8 1.8 1.8 1.8 1.8 2.0 2.0 2.0 643466 1.7 1.7 1.7 1.7 1.7 1.7 1.7 1.9 1.9 1.9 643332 1.7 1.7 1.7 1.7 1.7 1.7 1.7 1.9 1.9 1.9 643404 1.7 1.7 1.7 1.7 1.7 1.7 1.7 1.9 1.9 1.9 643408 1.9 1.9 1.9 1.9 1.9 1.9 1.9 2.1 2.1 2.1 643359 1.8 1.8 1.8 1.8 1.8 1.8 1.8 2.1 2.1 2.1 643340 2.0 2.0 2.0 2.0 2.0 2.0 2.0 2.1 2.1 2.1 643487 1.7 1.7 1.7 1.7 1.7 1.7 1.7 1.9 1.9 1.9 643356 2.0 2.0 2.0 2.0 2.0 2.0 2.0 2.2 2.2 2.2 643329 1.8 1.8 1.8 1.8 1.8 1.8 1.8 2.1 2.1 2.1 643388 1.6 1.6 1.6 1.6 1.6 1.6 1.6 1.9 1.9 1.9 643450 2.2 2.2 2.2 2.2 2.2 2.2 2.2 2.5 2.5 2.5 643467 2.0 2.0 2.0 2.0 2.0 2.0 2.0 2.3 2.3 2.3 643443 1.8 1.8 1.8 1.8 1.8 1.8 1.8 2.0 2.0 2.0 643417 2.2 2.2 2.2 2.2 2.2 2.2 2.2 2.5 2.5 2.5 643413 1.8 1.8 1.8 1.8 1.8 1.8 1.8 2.1 2.1 2.1 643338 2.0 2.0 2.0 2.0 2.0 2.0 2.0 2.2 2.2 2.2 643335 2.1 2.1 2.1 2.1 2.1 2.1 2.1 2.3 2.3 2.3 643468 1.8 - 1.8 1.8 1.8 1.8 1.8 1.8 2.0 2.0 2.0 643440 2.1 2.1 2.1 2.1 2.1 2.1 2.1 2.3 2.3 2.3 643430 1.8 1.8 1.8 1.8 1.8 1.8 1.8 2.0 2.0 2.0 643431 1.9 1.9 1.9 1.9 1.9 1.9 1.9 2.2 2.2 2.2 64336B 1.9 1.9 1.9 1.9 1.9 1.9 1.9 2.2 2.2 2.2 643326 2.0 2.0 2.0 2.0 2.0 2.0 2.0 2.3 2.3 2.3 643365 2.1 2.1 2.1 2.1 2.1 2.1 2.1 2.5 2.5 2.5 643375 2.1 2.1 2.1 2.1 2.1 2.1 2.1 2.5 2.5 2.5 643328 2.0 2.0 2.0 2.0 2.0 2.0 2.0 2.3 2.3 2.3 643348 1.7 1.7 1.7 1.7 1.7 1.7 1.7 2.0 2.0 2.0 643346 1.9 1.9 1.9 1.9 1.9 1.9 1.9 2.2 2.2 2.2 643449 2.2 2.2 2.2 2.2 2.2 2.2 2.2 2.4 2.4 2.4 643429 2.0 2.0 2.0 2.0 2.0 2.0 2.0 2.3 2.3 2.3 643424 1.9 1.9 1.9 1.9 1.9 1.9 1.9 2.1 2.1 2.1 643347 1.8 1.8 1.8 1.8 1.8 1.8 1.8 2.0 2.0 2.0 643456 2.1 2.1 2.1 2.1 2.1 2.1 2.1 2.5 2.5 2.5 643423 1.9 1.9 1.9 1.9 1.9 1.9 1.9 2.1 2.1 2.1 643345 1.8 1.8 1.8 1.8 1.8 1.8 1.8 2.0 2.0 2.0 643351 1.9 1.9 1.9 1.9 1.9 1.9 1.9 2.1 2.1 2.1 643358 1.9 1.9 1.9 1.9 1.9 1.9 1.9 2.2 2.2 2.2 643444 2.0 2.0 2.0 2.0 2.0 2.0 2.0 2.3 2.3 2.3 643474 1.7 1.7 1.7 1.7 1.7 1.7 1.7 1.9 1.9 1.9 643441 1.9 1.9 1.9 1.9 1.9 1.9 1.9 2.2 2.2 2.2 643481 1.7 1.7 1.7 1.7 1.7 1.7 1.7 1.9 1.9 1.9 560 Company Sanitized. Does not co H-24516: Subchronic Toxicity 90-Day Gavage Study in Rats with One-Generation Reproduction Evaluations INDIVIDUAL DOSE VOLUMES (mL) Day 12 Day 13 Day 14 Day 15 Day 16 Day 17 Day 18 Day 19 Day 20 Day 21 Day Female, VIII - 250 mg/kg/day 643341 2. 1 2.1 2.3 2.3 2.3 2.3 2.3 2.3 2.3 2.4 643370 2. 4 2.4 2.6 2.6 2.6 2.6 2.6 2.6 2.6 2.9 643446 2. 2 2.2 2.5 2.5 2.5 2.5 2.5 2.5 2.5 2.6 643435 2. 0 2.0 2.2 2.2 2.2 2.2 2.2 2.2 2.2 2.2 643466 1. 9 1.9 2.2 2.2 2.2 2.2 2.2 2.2 2.2 2.3 643332 1. 9 1.9 2.0 2.0 2.0 2.0 2.0 2.0 2.0 2.3 643404 1. 9 1.9 2.1 2.1 2.1 2.1 2.1 2.1 2.1 2.3 643408 2. 1 2.1 2.4 2.4 2.4 2.4 2.4 2.4 2.4 2.6 643359 2. 1 2.1 2.4 2.4 2.4 2.4 2.4 2.4 2.4 2.5 643340 2. 1 2.1 2.4 2.4 2.4 2.4 2.4 2.4 2.4 2.5 643487 1. 9 1.9 2.1 2.1 2.1 2.1 2.1 2.1 2.1 2.3 643356 2. 2 2.2 2.4 2.4 2.4 2.4 2.4 2.4 2.4 2.5 643329 2. 1 2.1 2.2 2.2 2.2 2.2 2.2 2.2 2.2 2.3 643388 1. 9 1.9 2.0 2.0 2.0 2.0 2.0 2.0 2.0 2.2 643450 2. 5 2.5 2.7 2.7 2.7 2.7 2.7 2.7 2.7 2.9 643467 2. 3 2.3 2.4 2.4 2.4 2.4 2.4 2.4 2.4 2.5 643443 2. 0 2.0 2.1 2.1 2.1 2.1 2.1 2.1 2.1 2.3 643417 2. 5 2.5 2.8 2.8 2.8 2.8 2.8 2.8 2.8 3.0 643413 2. 1 2.1 2.2 2.2 2.2 2.2 2.2 2.2 2.2 2.4 643338 2. 2 2.2 2.3 2.3 2.3 2.3 2.3 2.3 2.3 2.5 643335 2. 3 2.3 2.4 2.4 2.4 2.4 2.4 2.4 2.4 2.6 643468 2. 0 - 2.0 2.2 2.2 2.2 2.2 2.2 2.2 2.2 2.4 643440 2. 3 2.3 2.6 2.6 2.6 2.6 2.6 2.6 2.6 2.8 643430 2. 0 2.0 2.2 2.2 2.2 2.2 2.2 2.2 2.2 2.4 643431 2.,2 2.2 2.4 2.4 2.4 2.4 2.4 2.4 2.4 2.6 643368 2.,2 2.2 2.3 2.3 2.3 2.3 2.3 2.3 2.3 2.4 643326 2..3 2.3 2.5 2.5 2.5 2.5 2.5 2.5 2.5 2.6 643365 2,.5 2.5 2.7 2.7 2.7 2.7 2.7 2.7 2.7 2.9 643375 2 .5 2.5 2.8 2.8 2.8 2.8 2.8 2.8 2.8 2.9 643328 2 .3 2.3 2.6 2.6 2.6 2.6 2.6 2.6 2.6 2.7 643348 2 .0 2.0 2.2 2.2 2.2 2.2 2.2 2.2 2.2 2.4 643346 2 .2 2.2 2.3 2.3 2.3 2.3 2.3 2.3 2.3 2.5 643449 2 .4 2.4 2.8 2.8 2.8 2.8 2.8 2.8 2.8 2.9 643429 2 .3 2.3 2.6 2.6 2.6 2.6 2.6 2.6 2.6 2.7 643424 2 .1 2.1 2.3 2.3 2.3 2.3 2.3 2.3 2.3 2.5 643347 2 .0 2.0 2.2 2.2 2.2 2.2 2.2 2.2 2.2 2.2 643456 2 .5 2.5 2.7 2.7 2.7 2.7 2.7 2.7 2.7 2.9 643423 2 .1 2.1 2.3 2.3 2.3 2.3 2.3 2.3 2.3 2.3 643345 2 .0 2.0 2.3 2.3 2.3 2.3 2.3 2.3 2.3 2.4 643351 2 .1 2.1 2.3 2.3 2.3 2.3 2.3 2.3 2.3 2.4 643358 2 .2 2.2 2.4 2.4 2.4 2.4 2.4 2.4 2.4 2.5 643444 2 .3 2.3 2.4 2.4 2.4 2.4 2.4 2.4 2.4 2.6 643474 1 .9 1.9 2.2 2.2 2.2 2.2 2.2 2.2 2.2 2.2 643441 2 .2 2.2 2.4 2.4 2.4 2.4 2.4 2.4 2.4 2.6 643481 1 .9 1.9 2.2 2.2 2.2 2.2 2.2 2.2 2.2 2.3 561 Company Sanitized. Does not co H-24516: Subchronic Toxicity 90-Day Gavage Study in Rats with One-Generation Reproduction Evaluations INDIVI r 5UAIi DOE1Ei VOLUME;S (mL) Day 24 Day 25 Day 26 Day 27 Day 28 Day 29 Day 30 Day 31 Day 32 Day 33 Day Female, VIII - 250 mg/k.'3/day 643341 2.4 2.4 2.4 2.4 2.5 2.5 2.5 2.5 2 .5 2.5 643370 2.9 2.9 2.9 2.9 2.9 2.9 2.9 2.9 2.9 2.9 643446 2.6 2.6 2.6 2.6 2.7 2.7 2.7 2.7 2.7 2.7 643435 2.2 2.2 2.2 2.2 2.3 2.3 2.3 2.3 2.3 2.3 643466 2.3 2.3 2.3 2.3 2.5 2.5 2.5 2.5 2.5 2.5 643332 2.3 2.3 2.3 2.3 2.3 2.3 2.3 2.3 2.3 2.3 643404 2.3 2.3 2.3 2.3 2.4 2.4 2.4 2.4 2.4 2.4 643408 2.6 2.6 2.6 2.6 2.7 2.7 2.7 2.7 2.7 2.7 643359 2.5 2.5 2.5 2.5 2.8 2.8 2.8 2.8 2.8 2.8 643340 2.5 2.5 2.5 2.5 2.7 2.7 2.7 ' 2.-7 2.7 2.7 643487 2.3 2.3 2.3 2.3 2.4 2.4 2.4 2.4 2.4 2.4 643356 2.5 2.5 2.5 2.5 2.6 2.6 2.6 2.6 2.6 2.6 643329 2.3 2.3 2.3 2.3 2.4 2.4 2.4 2.4 2.4 2.4 643388 2.2 2.2 2.2 2.2 2.4 2.4 2.4 2.4 2.4 2.4 643450 2.9 2.9 2.9 2.9 3.0 3.0 3.0 3.0 3.0 3.0 643467 2.5 2.5 2.5 2.5 2.7 2.7 2.7 2.7 2.7 2.7 643443 2.3 2.3 2.3 2.3 2.5 2.5 2.5 2.5 2.5 2.5 643417 3.0 3.0 3.0 3.0 3.1 3.1 3.1 3.1 3.1 3.1 643413 2.4 2.4 2.4 2.4 2.5 2.5 2.5 2.5 2.5 2.5 643338 2.5 2.5 2.5 2.5 2.7 2.7 2.7 2.7 2.7 2.7 643335 2.6 2.6 2.6 2.6 2.8 2.8 2.8 2.8 2.8 2.8 643468 2.4 - 2.4 2.4 2.4 2.5 2.5 2.5 2.5 2.5 2.5 643440 2.8 2.8 2.8 2.8 2.9 2.9 2.9 2.9 2.9 2.9 643430 2.4 2.4 2.4 2.4 2.5 2.5 2.5 2.5 2.5 2.5 643431 2.6 2.6 2.6 2.6 2.7 2.7 2.7 2.7 2.7 2.7 643368 2.4 2.4 2.4 2.4 2.6 2.6 2.6 2.6 2.6 2.6 643326 2.6 2.6 2.6 2.6 2.8 2.8 2.8 2.8 2.8 2.8 643365 2.9 2.9 2.9 2.9 3.1 3.1 3.1 3.1 3.1 3.1 643375 2.9 2.9 2.9 2.9 3.1 3.1 3.1 3.1 3.1 3.1 643328 2.7 2.7 2.7 2.7 2.8 2.8 2.8 2.8 2.8 2.8 643348 2.4 2.4 2.4 2.4 2.5 2.5 2.5 2.5 2.5 2.5 643346 2.5 2.5 2.5 2.5 2.5 2.5 2.5 2.5 2.5 2.5 643449 2.9 2.9 2.9 2.9 3.0 3.0 3.0 3.0 3.0 3.0 643429 2.7 2.7 2.7 2.7 2.9 2.9 2.9 2.9 2.9 2.9 643424 2.5 2.5 2.5 2.5 2.5 2.5 2.5 2.5 2.5 2.5 643347 2.2 2.2 2.2 2.2 2.3 2.3 2.3 2.3 2.3 2.3 643456 2.9 2.9 2.9 2.9 2.9 2.9 2.9 2.9 2.9 2.9 643423 2.3 2.3 2.3 2.3 2.5 2.5 2.5 2.5 2.5 2.5 643345 2.4 2.4 2.4 2.4 2.5 2.5 2.5 2.5 2.5 2.5 643351 2.4 2.4 2.4 2.4 2.4 2.4 2.4 2.4 2.4 2.4 64335B 2.5 2.5 2.5 2.5 2.6 2.6 2.6 2.6 2.6 2.6 643444 2.6 2.6 2.6 2.6 2.8 2.8 2.8 2.8 2.8 2.8 643474 2.2 2.2 2.2 2.2 2.3 2.3 2.3 2.3 2.3 2.3 643441 2.6 2.6 2.6 2.6 2.7 2.7 2.7 2.7 2.7 2.7 643481 2.3 2.3 2.3 2.3 2.5 2.5 2.5 2.5 2.5 2.5 562 Company Sanitized. Do H-24516: Subchronic Toxicity 90-Day Gavage Study in Rats with One-Generation Reproduction Evaluations Day 36 Day 37 Female, 643341 643370 643446 643435 643466 643332 643404 643408 643359 643340 643487 643356 643329 643388 643450 643467 643443 643417 643413 643338 643335 64346B 643440 643430 643431 643368 643326 643365 643375 643328 643348 643346 643449 643429 643424 643347 643456 643423 643345 643351 643358 643444 643474 643441 643481 VIII - 250 ing/kg/day 2 .7 3 .2 2 .8 2 .4 2 .6 2 .5 2 .6 2 .7 2 .9 2 .8 2 .5 2 .6 2 .6 2 .4 3 .1 2 .8 2 .5 3 .1 2 .6 2 .8 3 .0 2 .6 3 .0 2 .6 2 .9 2 .7 2 .9 3 .2 3 .3 3 .0 2 .6 2 .8 3 .1 3 .0 2 .6 2.4 3 .1 2 .6 2 .5 2 .5 2 .7 2 .8 2 .4 2 .8 2 .5 2 .7 3 .2 2 .8 2.4 2 .6 2.5 2 .6 2 .7 2 .9 2 .8 2 .5 2 .6 2 .6 2 .4 3 .1 2 .8 2 .5 3 .1 2 .6 2 .8 3 .0 . 2 .6 3 .0 2 .6 2 .9 2 .7 2 .9 3 .2 3 .3 3 .0 2 .6 2 .8 3 .1 3 .0 2 .6 2 .4 3 .1 2 .6 2 .5 2 .5 2 .7 2 .8 2 .4 2 .8 2 .5 Day 38 2.0 2.4 2.1 1.8 1.9 1.9 1.9 2.0 2.2 2.1 1.9 2.0 1.9 1.8 2.3 2.1 1.9 2.4 1.9 2.1 2.2 2.0 2.2 1.9 2.2 2.0 2.2 2.4 2.4 2.3 1.9 2.1 2.3 2.2 2.0 1.8 2.3 1.9 1.9 1.9 2.0 2.1 1.8 2.1 1.9 Day 39 INDIVIDUAL DOSE VOLUMES (mL) Day 40 Day 41 Day 42 2 .0 2.0 2.0 2.1 2 .4 2.4 2.4 2.5 2 .1 2.1 2.1 2.2 1 .8 1.8 1.8 1.9 1 .9 1.9 1.9 2.1 1 .9 1.9 1.9 2.0 1 .9 1.9 1.9 2.0 2 .0 2.0 2.0 2.1 2 .2 2.2 2.2 2.2 2 .1 2.1 2.1 2.1 1 .9 1.9 1.9 1.9 2 .0 2.0 2.0 2.0 1 .9 1.9 1.9 2.1 1 .8 1.8 1.8 1.9 2 .3 2.3 2.3 2.4 2 .1 2.1 2.1 2.2 1 .9 1.9 1.9 2.0 2 .4 2.4 2.4 2.4 1 .9 1.9 1.9 2.0 2 .1 2.1 2.1 2.1 2 .2 2.2 2.2 2.3 2 .0 2.0 2.0 2.0 2 .2 2.2 2.2 2.3 1 .9 1.9 1.9 1.9 2 .2 2.2 2.2 2.3 2 .0 2.0 2.0 2.1 2 .2 2.2 2.2 2.2 2 .4 2.4 2.4 2.4 2 .4 2.4 2.4 2.5 2 .3 2.3 2.3 2.3 1 .9 1.9 1.9 2.0 2 .1 2.1 2.1 2.1 2 .3 2.3 2.3 2.4 2 .2 2.2 2.2 2.3 2 .0 2.0 2.0 2.0 1 .8 1.8 1.8 1.9 2.3 2.3 2.3 2.4 1 .9 1.9 1.9 2.0 1 .9 1.9 1.9 2.0 1 .9 1.9 1.9 1.9 2 .0 2.0 2.0 2.1 2 .1 2.1 2.1 2.3 1 .8 1.8 1.8 1.9 2 ..1 2.1 2.1 2.2 1.9 1.9 1.9 2.0 Day 43 2.1 2.5 2.2 1.9 2.1 2.0 2.0 2.1 2.2 2.1 1.9 2.0 2.1 1.9 2.4 2.2 2.0 2.4 2.0 2.1 2.3 2.0 2.3 1.9 2.3 2.1 2.2 2.4 2.5 2.3 2.0 2.1 2.4 2.3 2.0 1.9 2.4 2.0 2.0 1.9 2.1 2.3 1.9 2.2 2.0 Day 44 2.1 2.5 2.2 1.9 2.1 2.0 2.0 2.1 2.2 2.1 1.9 2.0 2.1 1.9 2.4 2.2 2.0 2.4 2.0 2.1 2.3 2.0 2.3 1.9 2.3 2.1 2.2 2.4 2.5 2.3 2.0 2.1 2.4 2.3 2.0 1.9 2.4 2.0 2.0 1.9 2.1 2.3 1.9 2.2 2.0 563 Company Sanitized. Does n H-24516: Subchronic Toxicity 90-Day Gavage Study in Rats with One-Generation Reproduction Evaluations Day 46 Day 47 Female, 643341 643370 643446 643435 643466 643332 643404 643408 643359 643340 643487 643356 643329 643388 643450 643467 643443 643417 643413 643338 643335 643468 643440 643430 643431 643368 643326 643365 643375 643328 643348 643346 643449 643429 643424 643347 643456 643423 643345 643351 643358 643444 643474 643441 643481 VIII - 250 2.1 2.5 2.2 1.9 2.1 2.0 2.0 2.1 2.2 2.1 1.9 2.0 2.1 1.9 2.4 2.2 2.0 2.4 2.0 2.1 2.3 2.0 2.3 1.9 2.3 2.1 2.2 2.4 2.5 2.3 2.0 2.1 2.4 2.3 2.0 1.9 2.4 2.0 2.0 1.9 2.1 2.3 1.9 2.2 2.0 ing/kg/day 2.1 2.5 2.2 1.9 2.1 2.0 2.0 2.1 2.2 2.1 1.9 2.0 2.1 1.9 2.4 2.2 2.0 2.4 2.0 2.1 2.3 2.0 2.3 1.9 2.3 2.1 2.2 2.4 2.5 2.3 2.0 2.1 2.4 2.3 2.0 1.9 2.4 2.0 2.0 1.9 2.1 2.3 1.9 2.2 2.0 Day 48 2. 1 2. 5 2. 2 1. 9 2. 1 2. 0 2. 0 2. 1 2. 2 2. 1 1. 9 2. 0 2. 1 1. 9 2. 4 2. 2 2. 0 2. 4 2. 0 2. 1 2. 3 2. 0 2. 3 1. 9 2. 3 2. 1 2. 2 2. 4 2. 5 2. 3 2. 0 2. 1 2.4 2. 3 2. 0 1. 9 2. 4 2. 0 2.0 1. 9 2.,1 2..3 1..9 2,.2 2,.0 INDIVIDUAL DOSE VOLUMES Day 49 Day 50 Day 51 (mL) Day 52 2.1 2.1 2.1 2.1 2.5 2.5 2.5 2.5 2.2 2.2 2.2 2.2 1.9 1.9 1.9 1.9 2.0 2.0 2.0 2.0 2.0 2.0 2.0 2.0 2.0 2.0 2.0 2.0 2.1 2.1 2.1 2.1 2.3 2.3 2.3 2.3 2.2 2.2 2.2 2.2 2.0 2.0 2.0 2.0 2.1 2.1 2.1 2.1 2.2 2.2 2.2 2.2 1.8 1.8 1.8 1.8 2.4 2.4 2.4 2.4 2.1 2.1 2.1 2.1 2.0 2.0 2.0 2.0 2.5 2.5 2.5 2.5 2.0 2.0 2.0 2.0 2.2 2.2 2.2 2.2 2.4 2.4 2.4 2.4 2.1 2.1 2.1 2.1 2.4 2.4 2.4 2.4 2.1 2.1 2.1 2.1 2.4 2.4 2.4 2.4 1.7 1.7 1.7 1.7 2.2 2.2 2.2 2.2 2.5 2.5 2.5 2.5 2.5 2.5 2.5 2.5 2.3 2.3 2.3 2.3 2.0 2.0 2.0 2.0 2.2 2.2 2.2 2.2 2.4 2.4 2.4 2.4 2.4 2.4 2.4 2.4 2.1 2.1 2.1 2.1 1.9 1.9 1.9 1.9 2.2 2.2 2.2 2.2 1.6 1.6 1.6 1.6 2.0 2.0 2.0 2.0 1.9 1.9 1.9 1.9 2.2 2.2 2.2 2.2 2.3 2.3 2.3 2.3 1.9 1.9 1.9 1.9 2.3 2.3 2.3 2.3 2.0 2.0 2.0 2.0 Day 53 Day 54 2 .1 2.1 2 .5 2. 2 .2 2. 1 .9 1. 2 .0 2.0 2 .0 2. 2 .0 2. 2 .1 2.1 2 .3 2. 2 .2 2. 2 .0 2.0 2 .1 2. 2 .2 2. 1 .8 1. 2 .4 2. 2 .1 2. 2 .0 2. 2 .5 2. 2 .0 2. 2 .2 2. 2 .4 2. 2 .1 2. 2 .4 2. 2 .1 2. 2 .4 2. AK TEST DAY 53 2 .2 2. 2 .5 2. 2 .5 2. 2 .3 2. 2 .0 2. 2 .2 2. 2 .4 2. 2 .4 2. 2 .1 2. 1 .9 1. 2 .2 2. 1 .6 1. 2 .0 2. 1 .9 1. 2 .2 2. 2 .3 2. 1 .9 1. 2 .3 2. 2 .0 2. 564 Company Sanitized. Does not H-24516: Subchronic Toxicity 90-Day Gavage Study in Rats with One-Generation Reproduction Evaluations Day 56 Day 57 Female, 643341 643370 643446 643435 643466 643332 643404 643408 643359 643340 643487 643356 643329 643388 643450 643467 643443 643417 643413 64333B 643335 643468 643440 643430 643431 643368 643326 643365 643375 643328 643348 643346 643449 643429 643424 643347 643456 643423 643345 643351 643358 643444 643474 643441 643481 VIII - 250 2.1 2.5 2.3 1.9 2.2 1.9 2.0 2.1 2.3 2.3 2.0 2.1 2.1 1.3 2.5 2.1 2.0 2.5 2.0 2.2 2.4 2.0 2.2 2.0 2.4 2.2 2.5 2.5 2.2 2.0 2.2 2.4 2.3 2.1 1.9 1.8 1.7 1.8 1.9 2.1 2.3 1.9 2.2 2.0 ing/kg/day 2.1 2.5 2.3 1.9 2.2 1.9 2.0 2.1 2.3 2.3 2.0 2.1 2.1 1.3 2.5 2.1 2.0 2.5 2.0 2.2 2.4 2.0 2.2 2.0 2.4 2.2 2.5 2.5 2.2 2.0 2.2 2.4 2.3 2.1 1.9 1.8 1.7 1.8 1.9 2.1 2.3 1.9 2.2 2.0 Day 58 2.1 2.5 2.3 1.9 2.2 1.9 2.0 2.1 2.3 2.3 2.0 2.1 2.1 1.3 2.5 2.1 2.0 2.5 2.0 2.2 2.4 2.0 2.2 2.0 2.4 2.2 2.5 2.5 2.2 2.0 2.2 2.4 2.3 2.1 1.9 1.8 1.7 1.8 1.9 2.1 2.3 1.9 2.2 2.0 INDIVIDUAL DOSE VOLUMES Day 59 Day 60 Day 61 (mL) Day 62 2.1 2.1 2.1 2.1 2.5 2.5 2.5 2.5 2.3 2.3 2.3 2.3 1.9 1.9 1.9 1.9 2.2 2.2 2.2 2.2 1.9 1.9 1.9 1.9 2.0 2.0 2.0 2.0 2.1 2.1 2.1 2.1 2.3 2.3 2.3 2.3 2.3 2.3 2.3 2.3 2.0 2.0 2.0 2.0 2.1 2.1 2.1 2.1 2.1 2.1 2.1 2.1 1.3 1.3 1.3 1.3 2.5 2.5 2.5 2.5 2.1 2.1 2.1 2.1 2.0 2.0 2.0 2.0 2.5 2.5 2.5 2.5 2.0 2.0 2.0 2.0 2.2 2.2 2.2 2.2 2.4 2.4 2.4 2.4 2.0 2.0 2.0 2.0 2.2 2.2 2.2 2.2 2.0 2.0 2.0 2.0 2.4 2.4 2.4 2.4 2.2 2.2 2.2 2.2 2.5 2.5 2.5 2.5 2.5 2.5 2.5 2.5 2.2 2.2 2.2 2.2 2.0 2.0 2.0 2.0 2.2 2.2 2.2 2.2 2.4 2.4 2.4 2.4 2.3 2.3 2.3 2.3 2.1 2.1 2.1 2.1 1.9 1.9 1.9 1.9 1.8 1.8 1.8 1.8 1.7 1.7 1.7 1.7 1.8 1.8 1.8 1.8 1.9 1.9 1.9 1.9 2.1 2.1 2.1 2.1 2.3 2.3 2.3 2.3 1.9 1.9 1.9 1.9 2.2 2.2 2.2 2.2 2.0 2.0 2.0 2.0 Day 63 2.1 2.3 2.3 1.9 2.1 1.9 2.0 2.0 2.4 2.1 2.0 2.2 2.2 1.8 2.5 2.1 2.0 2.4 2.1 2.2 2.3 2.0 1.8 2.0 2.5 1.9 2.5 2.5 2.1 1.9 2.3 2.4 2.3 2.1 2.0 2.3 1.9 2.0 1.6 2.2 2.0 1.9 2.0 2.0 Day 64 2.1 2.3 2.3 1.9 2.1 1.9 2.0 2.0 2.4 2.1 2.0 2.2 2.2 1.8 2.5 2.1 2.0 2.4 2.1 2.2 2.3 2.0 1.8 2.0 2.5 1.9 2.5 2.5 2.1 1.9 2.3 2.4 2.3 2.1 2.0 2.3 1. 2. 1. 2. 2. 1. 2. 2. 565 Company Sanitized. Does not H-24516: Subchronic Toxicity 90-Day Gavage Study in Rats with One-Generation Reproduction Evaluations Day 66 Day 67 Female, 643341 643370 643446 643435 643466 643332 643404 643408 643359 643340 643487 643356 643329 643388 643450 643467 643443 643417 643413 643338 643335 643468 643440 643430 643431 643368 643326 643365 643375 643328 643348 643346 643449 643429 643424 643347 643456 643423 643345 643351 643358 643444 643474 643441 643481 VIII - 250 2.1 2.3 2.3 1.9 2.1 1.9 2.0 2.0 2.4 2.1 2.0 2.2 2.2 1.8 2.5 2.1 2.0 2.4 2.1 2.2 2.3 2.0 1.8 2.0 2.5 1.9 2.5 2.5 2.1 1.9 2.3 2.4 2.3 2.1 2.0 2.3 1.9 2.0 1.6 2.2 2.0 1.9 2.0 2.0 mg/kg/day 2.1 2.3 2.3 1.9 2.1 1.9 2.0 2.0 2.4 2.1 2.0 2.2 2.2 1.8 2.5 2.1 2.0 2.4 2.1 2.2 2.3 2.0 1.8 2.0 2.5 1.9 2.5 2.5 2.1 1.9 2.3 2.4 2.3 2.1 2.0 2.3 1.9 2.0 1.6 2.2 2.0 1.9 2.0 2.0 Day 68 2.1 2.3 2.3 1.9 2.1 1.9 2.0 2.0 2.4 2.1 2.0 2.2 2.2 1.8 2.5 2.1 2.0 2.4 2.1 2.2 2.3 2.0 1.8 2.0 2.5 1.9 2.5 2.5 2.1 1.9 2.3 2.4 2.3 2.1 2.0 2.3 1.9 2.0 1.6 2.2 2.0 1.9 2.0 2.0 INDIVIDUAL DOSE VOLUMES (mL) Day 69 Day 70 Day 71 Day 72 2.1 2.1 2.1 2.1 2.3 2.2 2.2 2.2 2.3 2.3 2.3 2.3 1.9 1.9 1.9 1.9 2.1 2.2 2.2 2.2 1.9 2.0 2.0 2.0 2.0 2.1 2.1 2.1 2.0 2.1 2.1 2.1 2.4 2.4 2.4 2.4 FD TEST DAY 69 2.0 1.9 1.9 1.9 2.2 2.2 2.2 2.2 2.2 2.2 2.2 2.2 1.8 1.9 1.9 1.9 2.5 2.6 2.6 2.6 2.1 1.7 1.7 1.7 2.0 1.9 1.9 1.9 2.4 2.4 2.4 2.4 2.1 2.1 2.1 2.1 2.2 2.2 2.2 2.2 2.3 2.2 2.2 2.2 2.0 1.5 1.5 1.5 1.8 1.5 1.5 1.5 2.0 1.7 1.7 1.7 2.5 2.1 2.1 2.1 1.9 2.2 2.2 2.2 2.5 2.4 2.4 2.4 2.5 2.4 2.4 2.4 2.1 2.2 2.2 2.2 1.9 2.0 2.0 2.0 2.3 2.4 2.4 2.4 2.4 2.5 2.5 2.5 2.3 2.1 2.1 2.1 2.1 2.0 2.0 2.0 2.0 2.0 2.0 2.0 2.3 2.4 2.4 2.4 1.9 1.9 1.9 1.9 2.0 2.0 2.0 2.0 1.6 2.0 2.0 2.0 2.2 2.2 2.2 2.2 2.0 2.0 2.0 2.0 1.9 2.0 2.0 2.0 2.0 2.2 2.2 2.2 2.0 2.1 2.1 2.1 INDIVIDUAL DOSE VOLUMES (mL) Day 73 2.1 2.2 2.3 1.9 2.2 2.0 2.1 2.1 2.4 1.9 2.2 2.2 1.9 2.6 1.7 1.9 2.4 2.1 2.2 2.2 1.5 1.5 1.7 2.1 2.2 2.4 2.4 2.2 2.0 2.4 2.5 2.1 2.0 2.0 2.4 1.9 2.0 2.0 2.2 2.0 2.0 2.2 2.1 Day 74 2.1 2.2 2.3 1.9 2.2 2.0 2.1 2.1 2.4 1.9 2.2 2.2 1.9 2.6 1.7 1.9 2.4 2.1 2.2 2.2 1.5 1.5 1.7 2.1 2.2 2.4 2.4 2.2 2.0 2.4 2.5 2.1 2.0 2.0 2.4 1.9 2.0 2.0 2.2 2.0 2.0 2.2 2.1 566 Company Sanitized. Does not co H-24516: Subchronic Toxicity 90-Day Gavage Study in Rats with One-Generation Reproduction Evaluations Day 76 Day 77 Day 78 Day 79 Day 80 Female, VIII - 250 nig/kg/day 643341 2.1 2.0 2.0 2.0 2.0 643370 2.2 2.2 2.2 2.2 2.2 643446 2.3 2.3 2.3 2.3 2.3 643435 1.9 1.9 1.9 1.9 1.9 643466 2.2 2.1 2.1 2.1 2.1 643332 2.0 2.0 2.0 2.0 2.0 643404 2.1 2.0 2.0 2.0 2.0 643408 2.1 2.1 2.1 2.1 2.1 643359 2.4 2.5 2.5 2.5 2.5 643340 643487 1.9 1.7 1.7 1.7 1.7 643356 2.2b 2.2 2.2 2.2 2.2 643329 2.2 1.9 1.9 1.9 1.9 643388 1.9 1.8 1.8 1.8 1.8 643450 2.6 2.1 2.1 2.1 2.1 643467 643443 643417 643413 643338 643335 643468 643440 643430 643431 643368 643326 643365 643375 643328 643348 643346 643449 643429 643424 643347 2.0 2.0 2.0 2.0 2.0 643456 2.4 2.4 2.4 2.4 2.4 643423 1.9 1.9 1.9 1.9 1.9 643345 2.0 2.0 2.0 2.0 2.0 643351 2.0 2.1 2.1 2.1 2.1 643358 2.2 2.2 2.2 2.2 2.2 643444 2.0 2.1 2.1 2.1 2.1 643474 2.0 1.8 1.8 1.8 1.8 643441 2.2 2.3 2.3 2.3 2.3 643481 2-1 1.9 1.9 1.9 1.9 Day 81 2.0 2.2 2.3 1.9 2.1 2.0 2.0 2.1 2.5 1.7 2.2 1.9 1.8 2.1 2.0 2.4 1.9 2.0 2.1 2.2 2.1 1.8 2.3 1.9 Day 82 2.0 2.2 2.3 1.9 2.1 2.0 2.0 2.1 2.5 1.7 2.2 1.9 1.8 2.1 2.0 2.4 1.9 2.0 2.1 2.2 2.1 1.8 2.3 1.9 Day 83 2.0 2.2 2.3 1.9 2.1 2.0 2.0 2.1 2.5 1.7 2.2 1.9 1.8 2.1 2.0 2.4 1.9 2.0 2.1 2.2 2.1 1.8 2.3 1.9 Day 84 2.2 2.5 2.4 1.9 2.2 2.1 2.1 2.3 2.5 2.0 2.3 2.3 2.0 2.5 2.0 2. 2. 2. 2. 2. 2. 2. 2. 2. 567 Company SanKized. Does not c H-24516: Subchronic Toxicity 90-Day Gavage Study in Rats with One-Generation Reproduction Evaluations Day 86 Day 87 Female, 643341 643370 643446 643435 643466 643332 643404 643408 643359 643340 643487 643356 643329 643388 643450 643467 643443 643417 643413 643338 643335 643468 643440 643430 643431 643368 643326 643365 643375 643328 643348 643346 643449 643429 643424 643347 643456 643423 643345 643351 643358 643444 643474 643441 643481 VIII - 250 ing/kg/day 2 .2 2.2 2 .5 2.5 2.4 2.4 1 .9 1.9 2 .2 2.2 2 .1 2.1 2 .1 2.1 2 .3 2.3 2 .5 2.5 2 .0 2.0 2 .3 2.3 2 .3 2.3 2 .0 2.0 2 .5 2.5 2 .0 2.0 2 .6 2.6 2 .1 2.1 2.2 2.2 2 .1 2.1 2 .3 2.3 2 .3 2.3 2 .0 2.0 2 .5 2.5 2 .1 2.1 Day 88 2.2 2.5 2.4 1.9 2.2 2.1 2.1 2.3 2.5 2.0 2.3 2.3 2.0 2.5 2.0 2.6 2.1 2.2 2.1 2.3 2.3 2.0 2.5 2.1 INDIVIDUAL DOSE VOLUMES (mL) Day 89 Day 90 Day 91 Day 92 2.2 2.2 2.2 2.2 2.5 2.5 2.6 2.6 2.4 2.4 2.2 2.2 1.9 1.9 1.9 1.9 2.2 2.2 2.2 2.2 2.1 2.1 2.1 2.1 2.1 2.1 2.0 2.0 2.3 2.3 2.3 2.3 2.5 2.5 2.6 2.6 2.0 2.3 2.3 2.0 2.5 2.0 2.6 2.1 2.2 2.1 2.3 2.3 2.0 2.5 2.1 568 Company Sanitized. Does not co H-24516: Subchronic Toxicity 90-Day Gavage Study in Rats with One-Generation Reproduction Evaluations DuPont-5386 APPENDIX C INDIVIDUAL BODY WEIGHTS 569 Company Sanitized. Does not contain TSCA CBl H-24516: Subchronic Toxicity 90-Day Gavage Study in Rats with One-Generation Reproduction Evaluations INDIVIDUAL BODY WEIGHTS EXPLANATORY NOTES DuPont-5386 Critical Dates a^ Male and female rats designated for reproduction evaluations were co-housed. Body weights collected during the cohabitation and post-mating periods are reported in the Reproductive Toxicology section. Day 91 Male rats designated for the 90-day exposure period were sacrificed. Day 93 Female rats designated for 90-day exposure period were sacrificed. Day 119 Last day of non-fasted body weight data collection for rats designated for the one-month recovery period. Day 125 Male and female rats designated for the one-month recovery period were sacrificed Day 175 Last day of non-fasted body weight data collection for rats designated for the 3-month recovery period. Day 181 Male and female rats designated for 3-month recovery period were sacrificed. Abbreviations AK Accidentally Killed FD Found Dead SE Sacrificed in extremis 570 Company Sanitized. Does not contain TSCA CBI H-24516: Subchronic Toxicity 90-Day Gavage Study in Rats with One-Generation Reproduction Evaluations Day 0 Male, I - 0 ing/k9/day 643241 643300 643143 643205 643235 643288 643150 643189 643185 643210 643268 643232 643265 643239 643270 643148 643284 643229 643196 643176 643218 643207 643280 643271 643211 643163 643197 643242 643251 643155 643147 643276 643237 643226 643195 643246 643253 643262 643172 643303 643304 643162 643254 643145 643204 278. 0 237. 5 237. 1 262. 8 282. 1 246. 7 235. 8 253. 6 254. 9 254. 0 264. 6 263. 0 244. 5 274. 2 236. 7 246.4 277. 8 237. 8 207. 6 249. 3 265. 9 243.4 231. 5 257.2 253. 4 268. 6 252. 9 244. 2 244. 9 240.4 251. 3 281. 7 236. 4 245. 1 242. 2 298. 8 243. 1 254. 1 256. 0 227. 0 211. 2 227. 3 220. 3 248. 7 265. 6 Day 7 347 .0 296 .9 291 .5 313 .3 345 .3 311 .5 290 .4 323 .7 320 .6 304 .8 321 .1 309 .7 292 .8 336 .3 291.4 296.4 341 .8 282 .6 255 .6 300 .5 311 .9 285 .4 279 .3 317 .0 306.4 335.4 315 .7 307 .5 295 .6 294 .8 313 .7 352 .7 277 .9 290 .7 300 .1 357 .6 297 .0 311 .4 315 .6 286 .3 261 .4 284 .3 268 .7 291 .4 322 .1 Day 14 409.3 347.2 340.0 356.7 409.6 361.6 340.4 383.9 377.6 350.2 377.0 338.8 342.8 383.7 343.2 345.3 391.5 316.6 298.9 347.8 359.0 326.2 336.3 382.3 351.0 393.3 364.9 356.2 350.4 348.8 358.7 422.7 321.0 336.3 346.6 426.4 352.7 372.2 370.4 343.9 303.5 331.6 305.7 334.6 370.7 INDIVIDUAL BODY WEIGHTS (g) Day 21 Day 28 Day 35 451.2 392.9 381.3 409.0 459.2 413.8 362.3 431.3 422.4 392.1 433.9 381.3 396.9 429.6 384.1 382.5 432.3 352.1 330.0 392.6 402.9 359.2 375.5 425.2 392.3 443.0 415.5 401.4 389.9 389.5 396.8 466.9 360.2 367.4 380.9 467.6 404.2 421.4 426.6 389.2 338.4 365.0 334.2 369.7 407.6 497.6 423.9 419.4 447.6 511.4 459.6 383.1 468.9 . 459.8 427.6 468.7 396.6 416.7 464.4 414.4 412.6 473.6 371.3 351.7 427.3 434.6 389.8 407.6 470.9 423.7 482.2 445.2 434.9 417.9 415.4 434.0 502.7 390.9 396.2 407.6 501.7 431.4 452.5 463.9 433.7 370.3 391.1 366.5 397.1 447.8 522 .6 455 .5 442 .7 473.2 535 .6 488 .3 409 .2 492 .0 483 .3 444 .7 504 .2 410 .7 440 .4 489 .6 438 .3 445 .1 501 .1 388 .2 373 .4 451 .9 456 .5 420.4 442 .7 499 .1 445.2 524 .1 473 .0 464 .8 435 .3 432 .1 464 .8 542 .2 406 .0 413 .9 426 .8 533 .1 456 .5 493 .0 490 .3 471 .4 391 .1 415 .9 396 .8 433 .7 468 .8 Day 42 549 .7 483 .5 463 .6 504 .0 571 .7 514 .2 426 .9 520 .1 512 .9 471 .0 524 .6 428 .1 475 .7 522.0 461.4 459 .8 535 .2 410 .2 403 .1 480 .0 478 .7 434 .9 472 .2 531 .5 464 .3 548 .7 493 .2 497 .1 455 .0 454.4 486 .7 565 .8 429.5 440 .8 460 .0 562 .4 490 .6 517 .7 516 .2 502 .6 418 .0 426 .5 420 .8 459 .3 494 .1 Day 49 571.4 501.2 474.5 517.2 584.1 521.8 430.0 515.9 515.0 492.5 545.3 450.8 489.4 542.2 474.4 481.2 555.9 422.3 412.5 493.7 506.2 455.5 489.0 558.3 488.8 574.8 514.0 525.7 478.1 490.8 502.6 600.1 446.6 474.4 479.3 577.3 510.1 543.6 534.6 531.3 436.4 436.8 437.4 481.9 500.7 571 Compaq Sanitized. Does H-24516: Subchronic Toxicity 90-Day Gavage Study in Rats with One-Generation Reproduction Evaluations INDIVIDUAL BODY WEIGHTS (g) Day 63 Day 70 Male, I - 0 mg/kg/day 643241 643300 643143 643205 643235 643288 643150 643189 643185 643210 643268 643232 643265 643239 643270 643148 643284 643229 643196 643176 643218 643207 643280 643271 643211 643163 643197 643242 643251 643155 643147 643276 643237 643226 643195 643246 643253 643262 643172 643303 643304 643162 643254 643145 643204 607 .0 554 .5 496 .9 546 .8 622 .4 565 .9 461 .8 568 .6 5S6 .6 512 .5 558 .0 476 .2 489 .4 582 .8 502 .5 508 .0 597 .3 452 .8 442 .9 525 .7 548 .2 480 .5 536 .5 606 .7 518 .8 619 .7 553 .9 571 .0 514 .1 551 .5 539.4 646.7 479 .4 515 .0 523 .1 609 .6 545.9 573 .9 586 .1 568 .3 466 .6 401 .9 471 .1 495 .0 542 .5 621 .5 570 .0 508 .2 563 .6 632 .0 584 .2 474 .4 583.2 566 .5 528 .8 583 .0 490 .3 501 .0 600.6 508 .3 509 .9 620 .1 463 .8 451 .8 . 533 .9 558 .2 506 .4 557 .2 628 .5 533 .2 643 .8 568 .9 589 .1 524 .1 568 .0 564 .1 676 .8 490.4 530.2 540 .0 634 .0 570 .3 592 .2 607 .0 579 .8 480 .7 416 .8 481 .9 504 .0 557 .6 Day 74 603.0 510.3 512.4 629.2 469.0 458.8 534.3 568.8 504.9 563.1 624.9 531.3 644.0 573.1 586.3 531.5 593.7 562.4 682.3 478.3 Day 77 625.0 582.2 516.7 575.1 640.7 596.8 475.8 600.7 582.7 532.8 575.4 505.9 511.4 Day 84 637.6 594.8 522.5 584.9 657.5 607.1 485.5 613.5 600.6 551.0 589.5 524.7 511.0 505 .6 544 .4 545 .0 641 .7 579 .1 600 .4 620 .8 , 594 .0 496.4 378 .9 495 .6 564 .4 507.0 550.0 559.9 643.8 599.8 598.8 629.3 607.2 504.3 402.4 515.2 590.1 Day 90 640.6 601.4 524.1 593.0 665.2 602.7 492.0 628.9 610.2 546.8 573.8 530.6 "522 .9 510 .5 557.8 572 .6 661 .1 605 .5 608 .8 634 .6 616 .0 508 .2 413 .3 522 .0 595.4 Day 98 560.0 609.2 547.9 523.9 525.6 577.0 577.3 685.8 637.0 632.1 649.7 640.5 522.5 448.1 536.6 Day 105 576.6 631.3 533.8 528.2 526.7 594.0 591.4 696.6 645.3 654.2 663.2 657.4 532.4 417.3 544.3 572 Company Sanitized. Does no H-24516: Subchronic Toxicity 90-Day Gavage Study in Rats with One-Generation Reproduction Evaluations INDIVIDUAL BODY WEIGHTS (g) Male, I 643241 643300 643143 643205 643235 643288 643150 643189 643185 643210 643268 643232 643265 643239 643270 643148 643284 643229 643196 643176 643218 643207 643280 643271 643211 643163 643197 643242 643251 643155 643147 643276 643237 643226 643195 643246 643253 643262 643172 643303 643304 643162 643254 643145 643204 Day 119 - 0 ing/kg/day 596. 0 601.4 547. 3 533. 8 536.4 609. 3 '621. 1 702. 0 661. 4 678. 7 673. 0 671. 7 539. 2 434.2 555. 3 Day 126 578 .7 622 .5 548 .2 538 .2 549 .0 Day 133 600 .9 636 .3 556 .5 548 .9 569 .0 Day 140 600 .0 657 .5 578 .8 553 .5 573 .0 Day 147 610 .7 672 .6 593 .0 569 .2 546 .0 Day 154 616 .7 678 .3 601 .7 579 .6 558.4 Day 161 620 .1 693 .2 606 .0 579.4 573 .3 Day 168 618.8 697.8 621.4 574.1 583.2 573 Company SaniefceO. Does no H-24516: Subchronic Toxicity 90-Day Gavage Study in Rats with One-Generation Reproduction Evaluations INDIVIDUAL. BODY WEIGHTS (9) Male, I 643241 643300 643143 643205 643235 643288 643150 643189 643185 643210 643268 643232 643265 643239 643270 643148 643284 &43229 643196 643176 643218 643207 643280 643271 643211 643163 643197 643242 643251 643155 643147 643276 643237 643226 643195 643246 643253 643262 643172 643303 643304 643162 643254 643145 643204 Day 181 0 mg/k9/day 606.2 687.8 617.5 576.9 557.8 574 H-24516: Subchronic Toxicity 90-Day Gavage Study in Rats with One-Generation Reproduction Evaluations IND]:VIDlTAL BODY WE IGHTS (9) Day 10 Day 7 Male, III - 25 1ng/k9/day 643173 643290 643272 643292 643228 643308 643264 643240 643180 643179 643202 643310 643306 643305 643293 643287 643188 643230 643170 643144 643277 643214 643261 643166 643153 643177 643198 643291 643184 643167 643223 643233 643183 643219 643263 239 .1 214 .9 227 .0 246 .5 276 .0 259 .3 273 .4 254 .7 240 .6 261 .6 229 .4 259 .8 216 .0 272 .6 245 .5 205 .8 263 .6 261 .9 258 .0 192 .6 251 .8 261 .5 261 .6 231 .5 242 .3 242 .7 273.5 256 .8 241 .7 252 .6 255 .0 241.1 262 .6 269 .4 228 .7 302. 6 272. 0 277. 8 300. 7 346.4 326. 3 332. 3 302.4 302. 8 313. 9 281. 6 316. 0 259. 7 319.4 299. 3 255. 4 331. 6 310. 9 322. 2 243. 1 309. 3 325. 0 320. 0 278. 3 292. 7 305. 5 340. 7 318. 7 297. 3 315. 8 312. 5 287. 6 322. 4 327. 0 282. 5 Day 14 350. 3 323. 6 325.4 345. 8 407. 7 386. 4 390. 6 359. 8 362. 0 370. 9 327. 0 364. 2 301. 6 368. 2 352. 5 302. 0 396. 0 350. 4 374. 9 294. 6 365. 3 374. 6 384.2 337. 7 347.4 357. 8 402. 4 379. 9 340. 9 377.2 355. 7 329. 5 368. 7 383. 1 323. 1 Day 21 384. 9 357. 9 354. 9 386. 2 450. 9 424. 1 429. 0 377. 9 395. 4 410. 4 356. 7 413. 5 331. 0 401. 3 391. 4 337. 8 438.5 380. 0 412. 6 329. 2 415.2 415. 9 421. 9 372. 1 375. 3 402. 5 447. 9 418.5 369. 5 420. 1 391. 5 358. 1 404. 3 416. 9 356. 1 Day 28 423. 0 397. 1 394. 8 424. 0 493. 7 464. 8 465. 1 411. 6 437. 0 443. 9 384. 8 449. 6 365. 6 421. 8 422. 9 369. 6 479. 3 410. 3 449. 1 366. 6 455. 3 460. 9 449. 8 411.4 416. 0 439. 7 489. 6 459. 9 384. 5 451. 4 418.2 381. 9 444. 8 456. 9 388. 9 Day 3:5 470 .2 433.2 412 .3 457 .9 540.2 498 .7 504.4 433 .6 478 .1 462 .1 411 .0 475 .5 388 .1 456 .8 461 .6 397 .0 505 .2 433 .9 478 .6 385 .9 487 .5 487 .4 487 .0 443 .3 453.5 474 .8 522 .3 490 .4 396 .2 487 .2 440 .8 409 .5 480 .5 489 .3 416 .2 Day 42 477.0 462.5 434.7 483.0 560.1 520.4 527.8 446.3 509.5 479.6 428.5 494.6 407.9 468.8 479.7 412.1 522.5 444.8 498.5 409.2 516.2 505.8 503.9 457.3 460.1 492.0 536.6 513.4 413.5 500.3 462.4 422.4 505.7 511.2 430.1 Day 49 490. 5 472. 6 444. 7 489. 0 570. 3 529. 1 536. 6 445. 4 518. 4 480. 8 446. 9 502. 0 407.3 487. 3 499. 0 422. 8 547. 8 461. 7 513. 0 424. 6 535. 8 510. 3 524. 0 486. 6 470. 1 513. 4 563. 7 531. 7 420. 6 508.6 475. 0 428. 4 530. 2 532. 8 456. 4 575 Company Sanitized. Doe H-24516: Subchronic Toxicity 90-Day Gavage Study in Rats with One-Generation Reproduction Evaluations INDIVIDUAL BODY WEIGHTS (g) Day 63 Day 70 Male, III - 25 mg/kg/day 643173 643290 643272 643292 643228 643308 643264 643240 643180 643179 643202 643310 643306 643305 643293 643287 643188 643230 643170 643144 643277 643214 643261 643166 643153 643177 643198 643291 643184 643167 643223 643233 643183 643219 643263 524.4 513.5 487.6 520.8 625.8 564.5 589.3 468.4 554.5 495.5 448.4 535.0 426.4 512.2 540.9 448.0 602.5 489.3 546.0 456.7 582.8 548.6 569.2 526.3 511.4 549.2 589.5 568.2 433.2 537.4 502.2 440.6 565.1 572.6 479.7 528 .6 529 .0 504 .8 534 .8 646 .0 588 .3 603 .8 482 .3 553 .3 514 .6 459.8 554 .8 438 .1 530 .6 553.4 466 .8 614 .3 495 .6 564 .5 474 .3 600 .0 557 .6 591 .6 552 .5 525.4 562 .8 605 .3 591 .3 441.2 553 .7 516 .6 460 .8 576 .7 586 .0 493 .3 Day 74 464.4 627.9 498.8 562.9 469.4 604.5 574.2 594.0 559.7 536.0 566.0 624.1 593.3 461.8 555.7 523.6 480.3 585.6 587.9 495.4 Day 77 544.9 544.5 520.7 537.5 663.3 600.9 622.6 488.9 557.5 525.3 466.6 553.1 444.8 537.2 547.1 Day 84 540.5 561.0 538.4 536.4 685.3 625.9 635.0 499.6 576.5 541.1 471.6 565.6 461.3 543.1 553.5 Day 90 514.0 573.3 549.4 541.3 699.3 630.5 651.5 507.7 573.7 543.5 483.2 567.1 464.0 549.6 562.8 Day 98 489.9 581.8 482.5 564.1 579.5 Day 105 500.1 597.1 485.5 578.7 587.6 576 Company Sanitized. Qoes H-24516: Subchronic Toxicity 90-Day Gavage Study in Rats with One-Generation Reproduction Evaluations INDIVIDUAL BODY WBIGHTS (g) Day 119 Day 126 Male, III - 643173 643290 643272 643292 643228 643308 643264 643240 643180 643179 643202 643310 643306 643305 643293 643287 643188 643230 643170 643144 643277 643214 643261 643166 643153 643177 643198 643291 643184 643167 643223 643233 643183 643219 643263 25 mg/kg/day 509 .3 565 .5 471 .9 609 .8 606 .0 509 .9 572 .8 479 .5 590 .0 574 .3 Day 133 521 .6 595 .9 503 .7 581 .0 603 .1 Day 140 518.4 605.8 503.3 604.0 617.6 Day 147 525 .8 623 .0 514 .4 617 .7 628 .8 Day 154 532 .0 620.3 511 .9 630 .9 637 .5 Day 161 534 .7 626 .3 517 .1 638 .6 644 .0 Day 168 541 .9 635 .2 529 .6 653 .5 650 .3 577 Company Sanitized. Dees n H-24516: Subchronic Toxicity 90-Day Gavage Study in Rats with One-Generation Reproduction Evaluations INDIVIDUAL BODY WEIGHTS (g) Day 181 Male, III - 643173 643290 643272 643292 643228 643308 643264 643240 643180 643179 643202 643310 643306 643305 643293 643287 643188 643230 643170 643144 643277 643214 643261 643166 643153 643177 643198 643291 643184 643167 643223 643233 643183 643219 643263 25 mg/kg/day 523.6 618.7 514.8 644.7 620.2 578 H-24516: Subchronic Toxicity 90-Day Gavage Study in Rats with One-Generation Reproduction Evaluations INDIVIDUAL BODY WEIGHTS (g) Day 0 Day 7 Male, V - 100 nig/kg/day 643250 643243 643311 643318 643247 643175 643314 643275 643257 643224 643169 643159 643286 643181 643206 643313 6431B2 643146 643312 643193 643267 643216 643244 643245 643301 643200 643255 643157 643238 643227 643164 643154 643156 643208 643190 229 .7 230 .7 236 .3 260 .0 280 .3 260 .0 263 .1 271 .8 236 .3 253 .3 231 .9 267 .5 210 .0 280 .8 239 .5 206 .6 248 .0 275 .5 244 .2 241 .3 248 .4 271 .2 249 .9 231 .1 255 .1 244 .3 256 .6 241.6 257 .0 262 .7 250 .5 243 .9 266.4 245 .0 273 .7 275 .3 288 .5 297 .5 321 .5 353 .1 321 .8 328 .2 323 .6 302 .8 302 .9 277 .3 306 .7 252 .5 333 .0 286 .7 266 .7 310 .5 327 .6 303 .7 311 .3 310 .4 - 337.7 303.2 276 .2 311 .6 307 .8 314.2 295 .0 307 .2 330 .3 325 .4 297 .9 330 .2 302 .6 333 .5 Day 14 311 .4 347 .9 355 .8 373 .2 413 .5 370 .2 371 .5 365 .2 347 .1 341 .1 326 .1 356 .6 286 .5 377 .1 324 .4 315 .4 372 .2 373 .7 347 .0 373 .9 370 .9 398 .3 356 .6 313 .6 361 .5 361 .8 372 .5 347 .0 349 .9 380 .1 382 .1 340.4 381.4 347 .3 384 .1 Day 21. Day 28 352 .4 386 .2 385 .5 428 .9 449 .9 423 .3 410 .1 407 .2 387 .3 374 .5 367 .6 394 .2 327 .5 409 .5 366 .0 356 .1 421 .5 420 .0 383 .5 422 .1 418 .1 450 .8 392 .8 . 348.4 403 .0 402 .1 420 .5 387 .2 396 .5 411 .4 426 .5 , 387 .0 428 .0 390 .3 422.4 385 .1 420 .0 418 .7 462 .6 477 .0 453 .1 431 .8 447 .9 408 .9 404 .5 400 .8 431 .5 361 .4 437 .5 384 .6 394 .4 463 .8 , 452 .0 403 .6 466 .4 451.2 488 .1 426 .7 378 .3 439 .3 442 .9 460 .7 421 .9 411 .0 448 .5 471 .1 415 .0 467 .0 411 .9 450.4 Day 35 395.5 447.4 444.2 494.4 496.7 480.4 452.1 469.6 436.2 420.0 420.2 466.1 389.5 462.1 397.7 420.1 496.5 479.7 418.1 482.0 483.7 522.6 447.3 391.4 466.3 466.1 480.4 453.2 434.9 469.4 499.8 437.8 492.5 433.8 481.2 Day 42 408.9 469.2 466.3 512.8 526.4 503.8 477.8 488.0 451.8 436.4 439.8 480.7 411.9 490.6 418.0' 442.7 513.6 495.2 433.0 488.3 501.5 545.1 469.6 403.4 484.5 496.6 513.1 478.9 460.5 500.7 519.7 459.2 518.3 458.8 502.1 Day 49 422 .1 481 .1 475 .2 523 .8 480 .4 509 .0 492 .6 500 .2 459 .5 446 .2 449 .4 498 .9 435 .9 518 .5 443 .3 466 .4 528 .5 512 .3 439 .0 507 .9 533 .6 565.4 490 .9 418 .6 504 .1 511 .8 539 .6 503 .9 488 .2 531 .6 546 .4 480 .6 549 .9 481 .7 521.2 579 Corapanif Sanitized. Dse not co H-24516: Subchronic Toxicity 90-Day Gavage Study in Rats with One-Generation Reproduction Evaluations INDIVIDUAL BODY WEIGHTS (g) Day 63 Day 70 Male, V - 100 mg/kg/day 643250 643243 643311 643318 643247 643175 643314 643275 643257 643224 643169 643159 643286 643181 643206 643313 643182 643146 643312 643199 643267 643216 643244 643245 643301 643200 643255 643157 643238 643227 643164 643154 643156 643208 643190 458 .6 520 .0 494 .5 549 .9 527 .4 526 .3 516 .8 541 .3 485 .0 467 .1 448 .5 532 .6 471 .8 541 .8 460 .9 502.2 567.2 544 .7 486 .8 529 .0 545 .3 597 .9 520 .1 459 .4 540 .3 546 .4 583 .6 555 .1 528 .7 561 .0 581 .6 509 .0 598 .7 519 .4 567 .0 472 .1 532 .4 508 .7 563 .5 545 .3 454 .6 531 .0 560.5 496 .1 471 .5 469 .4 536 .5 484 .2 570 .7 473 .7 511 .2 582 .9 573 .3 502 .0 544 .7 568 .2 607 .6 514 .6 469 .9 559 .1 564.3 601 .7 575 .1 547.4 577 .4 602.5 516 .2 615 .1 529 .6 562 .5 Day 74 514.2 588.1 573.8 513.4 551.5 570.1 605.8 508.5 468.8 561.0 570.6 612.3 576.5 547.3 589.1 602.9 514.9 610.9 529.4 561.8 Day 77 Day 84 Day 90 470.0 543.5 511.3 570.8 555.9 397.4 538.2 562.2 501.5 480.8 475.8 544.8 490.8 590.3 472.9 485.1 548.3 519.3 575.6 562.6 AK TEST DAY 77 476.3 542.8 513.3 491.0 486.1 534.0 501.8 599.8 489.0 492.6 554.5 526.4 593.3 572.4 529.3 541.2 520.6 490.7 488.4 532.7 498.4 599.1 496.3 Day 98 506.9 545.3 496.8 588.8 501.8 Day 105 514.8 427.7 509.2 613.1 502.8 580 Company Sanitized. Dees not c H-24516: Subchronic Toxicity 90-Day Gavage Study in Rats with One-Generation Reproduction Evaluations INDIVIDUAL BODY WEIGHTS (g) Day 119 Day 126 Male, V - 100 mg/kg/day 643250 643243 643311 643318 643247 643175 643314 643275 643257 643224 643169 643159 643286 643181 643206 643313 643182 643146 643312 643199 643267 643216 643244 643245 643301 643200 643255 543157 643238 643227 643164 643154 643156 643208 643190 497 .5 515 .1 503 .2 636 .4 506 .4 517 .7 539 .7 461 .5 631 .3 505.3 Day 133 510. 3 555. 0 504.4 635. 1 520. 8 Day 140 523.2 574.0 527.3 657.0 521.1 Day 147 535 .0 587.4 544 .4 676 .0 532 .0 Day 154 548.3 609.0 556.8 688.4 533.0 Day 161 555 .9 611 .1 557.1 706 .6 542.4 Day 168 569 .3 620 .0 563 .7 738.4 548 .5 581 Company Sanitized Does no H-24516: Subchronic Toxicity 90-Day Gavage Study in Rats with One-Generation Reproduction Evaluations INDIVIDUAL BODY WEIGHTS (g) Day 181 Male, V - 100 nig/kg/day 643250 643243 643311 643318 643247 643175 643314 643275 643257 643224 643169 643159 643286 643181 643206 643313 643182 643146 643312 643199 643267 643216 643244 643245 643301 643200 643255 643157 643238 643227 643164 643154 643156 643208 643190 555.3 608.8 558.5 729.9 534.3 582 Company Sanitized. Does not co H-24516: Subchronic Toxicity 90-Day Gavage Study in Rats with One-Generation Reproduction Evaluations INDIVIDUAL BODY WEIGHTS (g) Day 0 Day 7 Male, VII - 250 ing/kg/day 643194 643252 643260 643315 643215 643193 643298 643201 643259 643174 643283 643149 643178 643152 643295 643289 643171 643158 643249 643161 643309 643248 643285 643278 643299 643274 643192 643222 643160 643191 643203 643282 643302 643317 643225 643296 643258 643316 643220 643236 643165 643266 643151 643234 643281 238.2 224.4 230.1 236.0 267.2 265.5 251.8 266.4 242.1 275.9 238.2 261.9 226.2 286.4 250.2 211.8 263.8 264.8 249.1 255.7 285.9 256.2 249.3 235.1 239.6 237.1 261.3 260.1 244.4 273.4 252.4 277.8 246.7 250.3 263.9 274.6 234.0 236.7 249.0 246.7 239.2 248.3 234.2 281.8 239.4 296.9 287.0 281.8 289.8 326.9 335.0 325.1 334.3 294.4 348.3 294.3 313.8 274.0 353.0 303.9 268.2 334.8 337.4 307.1 319.2 367.2 310.3 307.8 293.7 300.4 298.9 322.5 321.7 297.8 335.9 315.5 349.2 303.2 302.3 326.3 340.6 301.5 296.6 311.4 312.8 299.5 312.4 284.8 343.2 299.2 Day 14 336 .6 332 .4 320 .5 330 .8 372 .9 383.2 379.6 379 .8 344.4 394 .7 342 .9 356 .5 306 .3 412 .6 340 .2 307 .3 394 .0 388 .3 355 .1 362 .8 419 .8 350 .0 350 .4 337 .6 350 .8 348 .7 374 .0 366 .1 331 .5 381 .9 366 .7 410 .4 353.5 350 .8 371 .9 391 .8 352 .8 350 .5 360 .1 362 .7 354 .3 367 .0 326 .3 384 .9 342 .7 Day 21 382. 6 372. 1 352.4 372. 3 417. 5 433. 3 424. 0 429. 6 392. 9 449.4 371. 5 400. 3 338. 0 464. 9 381. 6 350. 7 452. 4 435. 2 390. 6 418. 9 472. 0 392. 0 386. 0 378. 3 391. 3 390. 7 419. 7 413. 4 375. 7 423. 0 417. 0 472. 5 393. 9 393. 4 407. 9 438. 5 401. 4 398.2 401. 7 410. 4 399. 1 412. 8 364. 6 427. 2 387. 8 Day 28 410 .4 404 .1 379 .5 402 .8 448 .1 461 .1 452 .9 462 .1 427 .9 485 .4 398.4 438 .8 293 .0 504 .9 406.6 380 .3 481 .7 463 .2 421 .9 453 .0 504 .2 419 .9 418 .6 408 .7 418 .1 422 .9 459 .2 444 .6 403. .0 443 .7 . 453 .8 510 .6 423 .4 423 .0 433 .1 469 .3 431.7 429 .9 432 .6 445 .4 432 .0 451 .1 396 .0 458 .1 422 .6 Day 35 432.4 433.9 395.6 428.6 468.1 479.9 478.7 494.2 451.3 519.7 419.7 466.9 318.3 531.9 432.8 404.3 509.5 494.3 462.4 486.5 529.5 442.6 440.5 427.5 441.2 453.2 491.9 471.4 422.8 460.0 481.1 536.8 445.5 446.3 454.4 495.8 456.2 455.8 447.4 453.8 460.5 482.7 415.6 494.4 451.1 Day 42 448.2 454.7 412.4 447.8 478.6 501.6 492.4 515.9 473.5 531.7 429.6 497.5 357.7 551.7 452.6 420.2 538.4 512.5 491.5 499.0 546.7 460.5 453.6 455.7 465.2 472.4 514.7 490.6 435.8 476.8 497.0 557.7 463.3 464.2 475.2 507.4 391.0 471.5 460.5 466.9 475.4 504.1 426.2 505.0 459.7 Day 49 463.5 440.2 410.4 447.5 473.4 503.5 496.8 502.7 471.6 534.4 420.4 509.1 354.8 570.6 456.0 426.6 543.2 533.8 498.0 511.7 558.3 457.8 460.7 449.7 477.0 484.5 523.2 495.6 450.4 488.8 505.9 586.7 474.5 473.1 477.6 518.9 439.6 485.6 471.7 481.2 458.4 519.9 437.9 525.8 483.8 583 Company SaniSteed. Does H-24516: Subchronic Toxicity 90-Day Gavage Study in Rats with One-Generation Reproduction Evaluations INDIVIDUAL BODY WEIGHTS (g) Day 63 Day 70 Male, VII - 250 mg/kg/day 643194 643252 643260 643315 643215 643193 643298 643201 643259 643174 643283 643149 643178 643152 643295 643289 643171 643158 643249 643161 643309 643248 643285 643278 643299 643274 643192 643222 643160 643191 643203 643282 643302 643317 643225 643296 643258 643316 643220 643236 643165 643266 643151 643234 643281 487.4 477.1 445.3 473.8 497.7 470.9 532.0 532.0 469.7 568.0 423.1 514.8 368.7 587.5 389.3 398.5 548.8 558.9 514.5 482.2 531.7 426.0 457.2 444.8 489.0 501.4 507.5 494.7 473.8 508.7 519.4 579.0. 458.2 477.3 497.9 539.4 479.0 505.6 437.7 481.6 434.2 534.5 431.8 489.4 508.1 501.3 369.1 446.4 489.8 426.3 485.5 537.0 532.0 495.7 578.6 394.7 523.6 369.4 595.6 337.8 423.4 453.0 573.0 457.9 478.4 487.8 396.8 439.9 474.1 480.2 502.0 518.2 520.8 480.4 511.1 530.9 499.3 375.0 393.0 511.2 427.7 480.1 504.8 444.3 500.0 460.8 537.4 427.7 437.7 510.8 Day 74 Day 77 373. 5 513. 8 561. 0 491. 4 462. 4 AK TEST' DAY 70 430. 7 434. 7 488. 8 438. 6 454. 9 529. 3 515. 9 472. 5 512. 5 487. 3 559. 5 414. 4 459.2 511. 7 502.9 451.7 453.5 463.5 487.2 506.9 492.7 549.4 453.6 580.3 440.3 527.4 351.7 595.9 420.7 509.0 515.4 416.0 502.3 455.7 485.3 393.2 525.3 396.1 504.5 Day 84 518.8 502.2 458.6 497.2 515.2 537.3 530.1 564.4 498.0 590.3 443.4 547.2 386.9 624.5 432.9 528.1 563.5 473.8 521.7 470.0 518.5 481.1 549.2 454.6 512.2 Day 90 532.9 530.3 463.6 501.1 533.1 562.2 544.4 576.8 509.9 596.3 471.1 543.9 394.5 628.3 456.8 545.3 581.2 498.5 528.7 476.1 543.5 508.2 564.1 458.5 503.6 Day 98 482 .4 549 .7 408 .2 643 .9 454 .9 555 .1 593 .9 512 .8 538 .2 483 .6 545 .0 536 .6 576 .8 476 .0 536 .2 Day 105 497.2 543.2 407.9 661.0 457.9 568.1 610.2 532.9 557.9 485.4 553.3 532.6 580.3 477.6 548.4 584 Company Sanitized. Does not H-24516: Subchronic Toxicity 90-Day Gavage Study in Rats with One-Generation Reproduction Evaluations INDIVIDUAL BODY WEIGHTS (g) Day 119 Day 126 Male, VII - 250 ing/kg/day 643194 643252 643260 643315 643215 643193 643298 643201 643259 643174 643283 643149 643178 643152 643295 643289 643171 643158 643249 643161 643309 643248 643285 643278 643299 643274 643192 643222 643160 643191 643203 643282 643302 643317 643225 643296 643258 643316 643220 643236 643165 643266 643151 643234 643281 483 .5 554 .9 411 .6 694 .2 466 .1 576.3 627.0 539.7 575.0 515.5 570.9 560.3 591.6 495.6 566.1 493 .1 550 .8 421 .1 708 .0 477 .0 Day 133 511 .7 574 .8 429 .9 726 .3 487 .8 Day 140 526 .6 582 .0 446 .5 728 .7 499.4 Day 147 547.4 609.1 454.5 743.7 513.4 Day 154 560.7 610.6 460.9 750.7 528.9 Day 161 567 .8 622 .9 470 .7 756 .5 551.5 Day 168 585.2 637.2 479.4 782.9 554.0 585 Company Sanitized. Does not co H-24516: Subchronic Toxicity 90-Day Gavage Study in Rats with One-Generation Reproduction Evaluations INDIVIDUAL BODY WEIGHTS (g) Day 181 Male, VII - 250 nig/kg/day 643194 643252 643260 643315 643215 643193 643298 643201 643259 643174 643283 643149 643178 643152 643295 643289 643171 643158 643249 643161 643309 643248 643285 643278 643299 643274 643192 643222 643160 643191 643203 643282 643302 643317 643225 643296 643258 643316 643220 643236 643165 643266 643151 643234 643281 S75.2 619.1 457.7 770.5 522.5 586 Gempanjf Sanitized. Boss not H-24516: Subchronic Toxicity 90-Day Gavage Study in Rats with One-Generation Reproduction Evaluations INEIIVXDXJAL B01DY WE IGHTS (g) Day 0 Day 7 Female, I I - 0 1ng/ki3/day 643477 643374 643406 643486 643361 643463 643398 643436 643362 643354 643402 643383 643465 643484 643384 643352 643343 643459 643394 643480 643319 643350 643363 643397 643421 643420 643419 643414 643401 643455 643378 643393 643447 643478 643386 643405 643425 643448 643426 643415 643453 643330 643336 643387 643377 173 .9 184 .0 161 .9 181 .9 189 .3 224 .2 174 .1 182 .1 184 .2 162 .0 178 .9 167.2 213 .8 177 .2 190 .9 185 .0 170 .9 212 .5 188 .6 197 .8 197 .9 186 .0 202 .8 185 .6 184 .2 207 .1 209 .9 209 .5 176 .5 191 .1 221 .0 194 .8' 191 .3 177 .5 183 .8 214 .9 202 .5 209 .3 183 .1 205.4 203 .0 172 .6 201 .4 191 .5 197 .9 202 .3 212 .6 185 .0 185 .2 214 .0 243 .9 188 .9 201.4 208.4 173.4 193 .2 189 .9 219 .3 194 .5 215 .3 214 .3 185 .4 228 .4 226 .2 226 .6 228 .3 206 .9 234 .0 225 .3 203 .9 234 .3 243 .5 246 .8 183 .6 213 .2 241 .8 228 .2 224 .8 201 .2 216 .5 240 .1 231 .0 229 .9 207 .8 243 .7 223 .1 188 .2 216 .4 211 .0 217 .5 Day 1'4 213 .3 230 .6 207 .7 190 .6 222 .4 265 .8 209 .5 225 .0 236 .4 191 .7 221 .3 204 .0 243 .7 210 .7 236 .1 229 .7 210.4 248 .5 238 .0 239 .1 241 .9 219 .7 256 .4 249.2 215 .5 250 .7 263 .2 261 .6 204 .5 223 .4 272 .9 244 .9 240 .8 209 .6 224 .3 265 .7 243.4 229 .8 231 .4 256 .1 252 .2 206 .3 247 .9 236 .9 237 .7 Day 2 1 236 .3 240 .1 216 .1 208 .4 258 .1 268 .1 229 .0 243 .1 253 .7 210 .1 233 .9 220 .5 266 .7 216 .6 249 .1 253.6 228 .8 257 .1 251 .0 253 .8 268 .5 229 .4 261 .7 262 .7 234.4 279 .8 286 .5 279 .7 205 .7 240 .7 286 .9 257 .4 257 .0 227 .7 239 .7 283 .8 266 .5 245 .3 259 .8 273 .9 269 .6 220 .9 265 .0 254 .7 264.4 Day 2 8 239 .5 246 .9 226 .2 208 .0 272 .6 292 .2 243 .0 258 .1 258 .8 217 .9 239 .9 219 .5 278 .2 233 .0 261 .6 262 .2 241 .5 273 .3 266.2 270 .1 273.2 243 .2 288 .6 270 .7 238 .9 285, .6 305 .0 291.4 227 .2 255 .4 300 .7 286 .9 269 .9 236 .6 251 .7 304 .6 278 .5 270 .4 273 .1 301 .4 279 .1 239 .0 290 .6 274 .2 273 .5 Day 35 264.5 256.5 243.6 221.8 284.2 305.4 262.2 271.7 276.8 226.2 248.3 238.0 274.2 236.7 279.6 280.2 262.6 285.3 277.0 286.8 293.7 253.5 302.6 277.2 253.9 319.5 324.2 307.3 234.0 257.2 321.8 300.3 289.4 243.3 254.8 318.5 292.7 281.9 291.4 296.6 290.8 254.1 298.5 294.2 285.9 Day 42 271.1 268.4 245.8 226.2 293.1 309.4 260.7 274.1 282.4 243.8 251.4 244.3 287.1 239.9 271.6 284.2 263.2 303.4 277.3 284.5 303.7 262.0 297.6 287.7 266.3 331.2 336.5 319.6 239.8 264.7 322.6 309.3 299.1 248.7 265.8 340.3 298.9 282.5 297.1 307.6 307.7 261.8 311.8 293.1 299.4 Day 49 272.7 279.9 255.2 237.6 318.8 308.3 272.0 276.8 285.2 259.4 267.0 259.7 297.7 249.6 284.3 295.4 274.4 316.6 291.1 289.9 309.9 274.8 315.1 301.9 270.9 347.8 349.3 330.3 244.3 272.6 344.7 319.4 307.8 261.0 269.7 354.6 307.3 280.5 301.9 315.4 315.2 266.3 318.1 307.0 309.7 587 Company Sanitized, Does not c H-24516: Subchronic Toxicity 90-Day Gavage Study in Rats with One-Generation Reproduction Evaluations Day 63 Day 70 Female, II - 0 nig/kg/day 643477 643374 643406 643486 643361 643463 643398 643436 643362 643354 643402 643383 643465 643484 643384 643352 643343 643459 643394 643480 643319 643350 643363 643397 643421 643420 643419 643414 643401 643455 643378 643393 643447 643478 643386 643405 643425 643448 643426 643415 643453 643330 643336 643387 643377 281 .2 292 .0 269 .3 260 .1 342 .4 333 .9 296 .2 288 .4 303 .9 272 .8 270 .0 278 .4 301 .6 251 .9 295 .6 298 .5 270 .5 313 .1 287 .6 298 .5 316 .1 288 .8 328 .8 296 .3 279 .2 358 .5 360 .0 344 .4 249 .6 276 .1 343 .3 333 .1 320 .0 271 .9 282 .2 354 .1 316 .2 310 .2 321 .8 347 .8 320 .1 276 .1 329 .7 323 .0 338 .8 285.9 304.5 276.6 264.3 353.0 336.2 297.9 298.9 305.2 280.0 274.9 290.1 314.4 255.6 299.1 306.6 288.4 323.6 293.9 294.6 318.4 292.4 327.9 304.9 286.5 358.2 358.2 355.4 263.0 278.1 342.8 335.7 325.9 268.0 282.2 367.3 326.1 310.7 333.9 373.1 333.4 281.3 329.7 333.3 338.4 Day 74 307.9 277.6 320.8 287.6 302.6 321.2 294.2 323.5 306.4 284.3 354.9 361.2 351.7 265.9 276.5 345.5 332.8 325.0 267.4 277.0 INDIVIDUAL BODY WEIGHTS (g) Day 77 Day 84 Day 91 284.0 313.1 273.0 263.3 359.9 336.7 295.6 301.7 309.7 283.8 271.2 297.3 314.8 260.0 303.2 286.8 313.7 272.5 257.9 378.1 341.3 303.8 307.2 315.8 284.8 286.0 296.9 324.1 268.0 311.0 297.9 327.7 280.6 249.7 395.0 351.3 309.2 323.9 312.4 286.8 280.1 301.1 324.8 267.4 299.3 358. 9 324.2 310. 6 341. 8 381.4 330. 6 279. 8 328. 3 330. 3 342. 4 360. 0 325.4 312. 6 349. 9 395. 9 334. 7 288. 5 332. 9 339. 9 339. 6 365.3 333.7 315.4 351.7 400.2 332.0 234.3 328.2 339.4 346.1 Day 98 280.8 282.9 329.8 266.7 319.0 377 .7 333 .3 346 .0 359 .8 418 .5 352 .3 269 .3 346 .5 349 .8 349 .0 Day 105 290.0 263.4 330.2 274.8 316.7 385.9 347.2 350.7 373.3 426.3 355.3 287.3 326.1 SE 367.2 361.7 588 H-24516: Subchronic Toxicity 90-Day Gavage Study in Rats with One-Generation Reproduction Evaluations Day 119 Day 126 Female, 643477 643374 643406 643486 643361 643463 643398 643436 643362 643354 643402 643383 643465 643484 643384 643352 643343 643459 643394 643480 643319 643350 643363 643397 643421 643420 643419 643414 643401 643455 643378 643393 643447 643478 643386 643405 643425 643448 643426 643415 643453 643330 643336 643387 643377 II - 0 mg/kg/day 287 .9 280 .1 318 .3 287 .1 319 .1 278 .4 281 .8 319 .5 281 .6 301 .8 389.5 384.6 350.9 395.3 450.3 368.2 301.9 SE TEST DAY 105 365.1 378.5 Day 133 293.4 296.8 331.6 296.9 323.4 INDIVIDUAL BODY WEIGHTS (g) Day 140 Day 147 Day 154 293 .8 303 .9 329.2 290 .9 321 .1 298 .5 313 .5 334 .5 302 .0 328 .0 295 .0 322 .1 349 .1 295 .1 320.2 Day 161 299 .2 322.7 352 .3 314 .9 325 .3 Day 168 305 .0 340 .6 356 .5 311 .9 334 .0 589 Company Sanitized. H-24516: Subchronic Toxicity 90-Day Gavage Study in Rats with One-Generation Reproduction Evaluations Day 181 Female, II - 0 nig/kg/day 643477 643374 643406 643486 643361 643463 643398 643436 643362 643354 643402 643383 643465 643484 643384 643352 643343 643459 643394 643480 643319 643350 643363 643397 643421 643420 643419 643414 643401 643455 643378 643393 643447 643478 643386 643405 643425 643448 643426 643415 643453 643330 643336 643387 643377 294.9 312.7 345.9 294.6 315.0 INDIVIDUAL BODY WEIGHTS (9) 590 Company Sanitized. Doe H-24516: Subchronic Toxicity 90-Day Gavage Study in Rats with One-Generation Reproduction Evaluations Day 0 Day 7 Female, IV - 25 mg/kg/day 643390 643396 643380 643433 643389 643410 643321 643324 643458 643364 643483 643411 643379 643391 643437 643399 643334 643464 643369 643490 643342 643438 643445 643418 643325 643479 643403 643376 643422 643452 643475 643372 643400 643395 643457 175 .0 201 .1 174 .8 193 .5 184.4 194 .5 193 .2 175 .9 179 .6 175 .9 184 .6 173 .3 208 .1 168 .6 192 .5 183 .9 169 .8 208 .9 200 .3 205 .8 202 .8 196 .6 225 .8 185 .1 224 .1 194 .4 194.4 190 .4 195 .7 205 .7 217 .1 204 .9 165 .8189 .6 198 .5 189 .2 231 .6 194 .6 218 .3 207 .5 228 .9 208 .1 202 .3 194 .8 186 .6 202 .4 AK TEST DAY 0 224 .3 187 .7 204 .3 196 .2 185 .7 237 .1 218 .2 225 .2 230 .0 215 .2 262 .3 206 .4 251 .8 219 .9 228 .8 219 .8 230 .4 218 .5 251 .8 223 .3 189 .0 209 .2 225 .8 Day 14 201.5 254.6 233.7 240.2 215.6 238.2 209.3 219.8 216.2 209.7 214.9 239.8 205.8 223.1 227.6 214.4 255.4 237.1 247.8 254.8 237.3 273.5 226.6 270.8 228.9 251.3 237.0 256.1 244.2 249.4 242.0 199.8 230.4 245.3 INDIVIDUAL BODY WEIGHTS (g) Day 21 Day 28 Day 35 Day 42 223 .6 284 .1 247.0 268 .4 236 .2 264 .3 233 .8 242 .6 230 .8 227 .7 225 .2 269 .2 218 .0 246 .3 242 .2 239 .4 275 .7 258 .7 266 .7 274 .1 249 .4 302 .3 242 .2 298 .1 256 .2 273 .9 256 .7 276 .5 274 .0 276 .7 263 .6 212 .9 253 .0 255 .0 240 .3 283 .8 265 .5 285 .2 240 .3 274 .9 236 .7 256 .0 244 .4 239 .4 228 .9 270 .0 231 .8 253 .8 256 .1 247 .4 291 .9 291 .2 278 .7 287 .5 279 .3 314 .5 261 .8 305 .3 264 .5 282 .1 268 .8 300 .1 300.. 6 288.2 276 .4 .228.2 256 .8 267 .1 249. 5 303. 4 275. 9 294. 2 262. 0 288. 1 SE TEST DAY 29 270. 0 258. 1 248. 0 247. 9 279. 4 239. 2 260. 0 268. 5 260. 8 304. 4 294. 0 284. 8 299. 1 286. 0 351. 5 270. 4 319. 3 278. 4 296. 8 274. 4 313. 3 305. 0 303. 7 285.2 241. 3 268. 9 275. 1 257 .3 307 .5 282 .5 305 .4 275 .2 301 .2 266 .3 264 .3 258 .9 254 .2 283 .5 253 .1 275 .6 280 .0 273 .3 314 .2 285 .1 295 .3 317 .5 298 .1 366 .9 289 .1 334 .5 285.4 306.4 293.5 325.4 315 .9 329 .3 290 .5 247 .3 271 .0 289 .3 Day 49 270 .2 312 .3 293 .3 308 .7 280.6 312 .6 278 .5 266.4 267 .1 260 .4 303 .0 254.4 281 .5 287 .8 277 .8 324 .0 311 .8 299 .6 324 .0 297 .6 380.6 299 .1 336 .9 289 .3 322 .7 296 .5 335 .0 323 .2 336 .5 267 .3 251 .2 282 .9 291 .5 591 Company Sanitized. Does not certai H-24516: Subchronic Toxicity 90-Day Gavage Study in Rats with One-Generation Reproduction Evaluations Day 63 Day 70 Female, IV - 25 mg/kg/day 643390 643396 643380 643433 643389 643410 643321 643324 643458 643364 643483 643411 643379 643391 643437 643399 643334 643464 643369 643490 643342 643438 643445 643418 643325 643479 643403 643376 643422 643452 643475 643372 643400 643395 643457 283 .6 334 .4 304 .9 330 .6 292 .7 312 .4 290 .8 279 .5 274 .3 268 .7 308 .4 275 .7 289 .3 289 .7 287 .8 327 .6 309 .2 298 .6 330 .8 302 .6 392-2 296 .2 355 .4 301 .4 317 .5 305 .7 355 .1 344 .7 339 .2 298 .9 272 .4. 287 .6 300.2 281 .6 349 .3 319 .6 341 .4 306 .2 316 .7 289 .9 295 .4 285 .8 271 .5 312 .3 282 .5 303 .5 302 .5 294 .6 328 .9 314.2 309 .9 335 .1 313 .8 - 398.6 305 .9 365 .2 295 .7 318 .8 307 .8 . 356 .1 343 .7 331 .6 305 .3 266 .8 293 .4 310 .1 Day 74 301 .2 292 .5 328 .3 312 .9 306 .0 337 .8 305 .3 395 .9 302 .5 368 .6 307 .5 274 .5 311 .1 360 .7 341 .2 341 .2 310 .8 269 .0 294 .6 303 .2 INDIVIDUAL BODY WEIGHTS (g) Day 77 Day 84 Day 91 288.3 355.7 322.6 349.5 298.3 319.8 294.8 300.6 295.2 267.6 304.9 278.7 298.3 291.1 361.8 331.7 348.7 295.8 325.7 304.5 299.7 299.8 273.0 304.7 284.7 300.4 286.8 359.1 328.6 353.5 290.1 323.4 303.1 303.1 296.5 280.9 312.6 294.6 302.8 Day 98 288.4 330.0 294.7 309.3 Day 105 283.7 329.7 297.8 319.4 592 Company Sanilteed. Does not co H-24516: Subchronic Toxicity 90-Day Gavage Study in Rats with One-Generation Reproduction Evaluations Day 119 Day 12S Female, IV - 25 mg/kg/day 643390 643396 643380 643433 643389 643410 643321 643324 643458 643364 643483 643411 643379 643391 643437 643399 643334 643464 643369 643490 643342 643438 643445 643418 643325 643479 643403 643376 643422 643452 643475 643372 643400 643395 643457 293.3 346.9 317.0 325.5 289.2 345.8 315.7 320.1 Day 133 298.2 358.8 321.9 330.6 INDIVIDUAL BODY WEIGHTS (g) Day 140 Day 147 Day 154 294.8 365.1 329.7 344.4 307.3 376.2 326.5 344.8 314.6 371.9 340.6 349.9 Day 161 309.8 380.4 334.1 353.0 Day 168 313.3 387.9 337.7 355.6 593 Company Sanitized. Does not H-24516: Subchronic Toxicity 90-Day Gavage Study in Rats with One-Generation Reproduction Evaluations Day 181 Female, IV - 25 mg/kg/day 643390 643396 643380 643433 643389 643410 643321 643324 643458 643364 643483 643411 643379 643391 643437 643399 643334 643464 643369 643490 643342 643438 643445 643418 643325 643479 643403 643376 643422 643452 643475 643372 643400 643395 643457 299.7 368.1 326.8 343.1 INDIVIDUAL BODY WEIGHTS (g) 594 Company Sanitized. Does noS c H-24516: Subchronic Toxicity 90-Day Gavage Study in Rats with One-Generation Reproduction Evaluations Day 0 Day 7 Female, VI - 100 ing/kg/day 643322 643489 643409 643366 643367 643461 643462 643392 643472 643323 643412 643382 643381 643360 643373 643320 643488 643428 643439 643353 643385 643339 643473 643337 643416 643407 643357 643331 643427 643470 643434 643349 643454 643333 643460 186 .5 184 .6 171 .5 173 .6 194 .9 214 .8 203 .2 164 .8 174 .8 166 .7 184 .6 180 .3 184 .9 161 .6 192 .7 179 .7 178 .2 218 .7 193.5 186 .8 202 .1 177 .0 175 .8 208 .5 183 .3 210 .7 166 .3 192 .8 187 .4 185 .5 199 .9 201 .3 200 .7 . 184 .6 194 .0 212 .9 203 .1 198 .5 202 .4 220 .2 255 .4 228 .9 180 .3 197 .1 191 .8 213 .6 202.4 206 .0 184 .6 226 .1 212 .1 206 .3 237 .1 216 .6 215 .2 222 .8 205 .0 200 .8 240 .9 206 .6 220 .8 196 .0 211 .6 . 210 .6 198 .9 220 .0 221 .1 219 .1 206 .3 224 .8 Day 14 230 .5 221 .6 221 .2 213 .3 234.2 276 .3 250 .1 197 .1 207 .6 212 .9 232 .9 207 .8 218 .5 201 .6 236 .1 233 .1 223 .6 275 .6 236 .5 231 .0 253 .3 229.4 218 .6 259 .5 228 .8 253 .6 213 .2 227.4 232 .6 226 .9 228 .4 249 .5 244 .1 229 .1 248 .5 INDIVIDUAL BODY WEIGHTS (g) Day 21 Day 28 Day 35 247 .8 243 .7 230 .7 233 .0 258 .0 294 .8 272 .3 214 .9 219 .9 234 .8 250 .0 234 .6 236 .7 222 .1 266 .0 252 .5 239 .9 278 .4 252 .6 241 .2 267 .7 234 .1 226 .0 285 .9 244 .2 273 .9 219 .7 240 .7 248 .6 240 .9 250 .6 261 .8 253 .5 239 .7 261 .3 261 .8 240 .7 246 .6 248 .9 268.4 300 .1 282.4 223 .3 232 .9 243 .8 253 .0 198 .4 244 .1 233 .0 279 .9 263 .7 260 .9 300 .3 263 .9 261 .5 280 .8 262.1 243 .6 311 .0 257 .9 293 .9 245 .7 256 .8 251 .8 261 .5 262 .9 281 .6 263 .6 243 .9 275 .1 271.3 262.6 262.5 264.0 279.4 324.3 287.8 236.7 242.0 248.0 259.9 196.4 249.2 222.3 279.0 278.5 263.9 307.3 275.1 273.7 293.4 267.5 251.3 284.4 264.2 297.9 254.1 270.6 270.3 269.2 273.5 294.9 279.9 260.7 289.0 Day 42 280 .8 262 .8 261 .6 283 .5 279 .6 331 .7 294 .8 255 .7 259 .0 266.2 270 .9 188 .6 263 .6 248 .7 300 .4 296 .5 275.4 319 .7 283 .2 277 .8 292.4 283 .5 267 .8 275 .3 269 .3 310 .8 273 .1 284 .7 282 .3 285 .2 277 .2 300 .6 296.4 263 .3 302 .4 Day 49 278 .3 284 .1 269 .5 285 .5 287 .3 314 .7 299 .7 251 .1 250 .8 255 .7 273 .0 224 .8 268 .6 256 .5 307 .0 296 .9 283 .0 322 .4 289 .5 303.2 310 .7 290 .7 267 .3 308 .9 275 .6 317 .0 274 .9 299.4 282 .3 289 .4 293 .2 306 .8 305 .5 275 .0 310 .4 595 Company SanfcA Does no H-24516: Subchronic Toxicity 90-Day Gavage Study in Rats with One-Generation Reproduction Evaluations Day 63 Day 70 Female, VI - 100 mg/kg/day 643322 643489 643409 643366 643367 643461 643462 643392 643472 643323 643412 643382 643381 643360 643373 643320 643488 643428 643439 643353 643385 643339 643473 643337 643416 643407 643357 643331 643427 643470 643434 643349 643454 643333 643460 289 .7 290 .2 272 .4 297 .5 292 .2 327 .7 305 .1 264 .3 262 .5 274 .2 285 .9 238 .9 274 .3 251 .7 307 .2 305 .6 290 .1 318 .3 293 .9 309 .2 308 .6 299 .4 269 .8 319 .2 284 .1 330 .6 285 .5 307 .5 284 .5 305 .4 284 .7 316 .7 304 .0 275 .8 317 .1 2.90 .8 312 .1 272 .6 305 .7 304 .5 320 .5 315 .7 274 .5 264 .9 290 .8 296 .4 252 .4 282 .7 264 .8 300 .3 316 .3 293 .2 315 .6 292 .5 313 .7 315 .1 306 .1 278 .1 338 .6 280 .4 325 .5 288 .0 317 .3 290 .3 308 .8 281 .6 313 .4 313 .6 284 .2 316 .9 Day 74 316 .2 296 .9 314 .7 290.6 310 .0 323 .7 311 .0 274 .0 298.5 274 .5 327 .7 291 .0 317 .5 286 .8 310 .7 291 .6 315 .1 309 .9 280 .5 315 .3 INDIVIDUAL BODY WEIGHTS (9) Day 77 Day 84 Day 91 295.4 315.7 278.2 307.6 302.7 324.3 314.9 275.9 263.4 290.4 293.6 257.3 284.2 260.8 317.6 294.0 315.0 276.7 311.5 305.7 316.9 320.3 271.2 270.1 293.3 302.8 . 254.5 298.9 261.2 311.3 295.7 319.2 281.9 313.0 315.0 328.1 318.3 277.0 270.6 286.1 300.7 258.5 296.6 261.3 314.5 Day 98 306.2 270.7 298.2 256.5 301.6 Day 105 306.5 276.0 301.9 267.9 305.8 596 Company Sanitized. Does no H-24516: Subchronic Toxicity 90-Day Oavage Study in Rats with One-Generation Reproduction Evaluations Day 119 Day 126 Female, VI 100 mg/kg/day 643322 643489 643409 643366 643367 643461 643462 643392 643472 643323 643412 643382 643381 643360 643373 643320 643488 643428 643439 643353 643385 643339 643473 643337 643416 643407 643357 643331 643427 643470 643434 643349 643454 643333 643460 321 .8 220 .5 312 .3 242 .5 313 .6 317 .8 263 .9 311 .3 248 .1 325 .1 Day 133 317 .5 277 .8 329 .7 265 .7 316 .3 INDIVIDUAL BODY WEIGHTS (g) Day 140 Day 147 Day 154 323 .5 278 .1 321 .6 265 .2 327 .2 333 .9 281 .1 327 .2 269 .6 342 .7 334 .4 281 .5 342 .6 283 .6 338 .3 Day 161 339 .7 291 .7 338 .9 280 .0 348 .5 Day 168 341.4 293.1 342.1 281.5 351.7 597 Company Does no H-24516: Subchronic Toxicity 90-Day Gavage Study in Rats with One-Generation Reproduction Evaluations Day 181 Female, VI - 100 nig/kg/day 643322 643489 643409 643366 643367 643461 643462 643392 643472 643323 643412 643382 643381 643360 643373 643320 643488 643428 643439 643353 643385 643339 643473 643337 643416 643407 643357 643331 643427 643470 643434 643349 643454 643333 643460 327.2 286.1 328.1 277.7 356.8 INDIVIDUAL BODY WEIGHTS (g) 598 Company Saniteed. Does not contain TS H-24516: Subchronic Toxicity 90-Day Gavage Study in Rats with One-Generation Reproduction Evaluations Day 0 Day 7 Female, VIII - 250 mg/kg/day 643341 643370 643446 643435 643466 643332 643404 643408 643359 643340 643487 643356 643329 643388 643450 643467 643443 643417 643413 643338 643335 643468 643440 643430 643431 643368 643326 643365 643375 643328 643348 643346 643449 643429 643424 643347 643456 643423 643345 643351 643358 643444 643474 643441 643481 186.4 202.6 195.9 181.0 168.9 173.1 166.9 191.2 184.7 196.2 169.0 196.1 180.8 164.2 224.7 197.0 181.1 217.9 181.7 197.2 205.9 175.6 211.6 181.8 190.6 188.2 196.4 209.8 206.8 201.9 172.8 193.0 216.0. 204.2 189.5 175.6 205.8 188.1 178.2 186.6 189.9 203.8 168.8 192.9 171.0 212 .8 239 .1 221 .5 198 .5 192 .0 187 .3 190 .0 211 .5 212 .0 213 .7 194 .4 215 .4 210 .2 185 .1 246 .4 226 .2 201 .7 250 .1 208 .0 220 .0 230.4 196 .4 234 .6 198 .0 220 .0 215 .3 227 .8 245 .4 . 253 .5 *,233 .3 196 .1 215 .4 237 .4 227 .7 213 .7 197 .7 251 .0 210 .9 203 .9 207 .0 215 .8 229 .6 189 .3 221 .5 190 .9 Day 14 233.2 261.6 246.1 216.8 217.0 202.0 211.3 240.5 239.1 244.9 210.4 236.2 220.6 204.0 266.1 240.3 213.8 278.8 221.6 234.7 244.6 223.4 261.2 223.5 243.6 234.9 249.3 271.6 275.5 256.6 217.5 232.4 275.6 258.2 232.5 224.4 274.7 230.8 227.9 226.9 235.4 244.6 217.8 244.5 220.3 INDIVIDUAL BODY WEIGHTS (g) Day 21 Day 28 Day 35 244.7 294.3 256.2 224.9 234.4 227.1 227.2 257.6 249.3 252.2 231.3 250.6 227.3 222.6 291.6 252.2 230.6 298.3 242.8 251.0 264.1 237.1 284.3 235.3 261.0 237.1 261.7 293.6 292.2 268.0 236.5 250.4 288.9 272.6 245.3 222.7 288.9 230.3 242.4 235.8 254.4 255.8 221.8 256.7 230.8 252 .1 289 .3 268 .3 234 .3 251 .6 232 .4 244 .1 268 .5 278.2 269 .5 240 .8 259 .1 236 .8 238 .4 300 .9 270 .5 245 .8 314 .8 251 .7 265 .5 281 .5 250 .6 290 .3 246 .3 274 .8 259.4 281 .8 310 .1 313 .9 276 .1 253 .8 253 .1 299 .7 289 .3 249.2 232 .8 289 .7 252 .4 246 .9 235 .6 262 .5 275 .1 230 .0 270 .1 245 .1 266.7 318.3 282.7 241.2 257.1 251.3 257.4 270.6 289.4 282.0 252.7 262.6 255.5 240.6 310.2 278.2 251.6 314.6 257.9 278.4 296.5 261.7 298.1 257.8 288.5 267.9 290.7 321.3 326.1 301.4 259.6 275.3 310.2 297.3 263.1 241.7 312.7 259.2 251.5 247.7 269.1 284.2 235.1 280.7 254.0 Day 42 276.0 334.2 289.1 248.6 279.8 268.7 260.3 285.3 294.2 280.0 259.7 267.0 275.6 253.4 320.1 287.0 261.6 322.6 262.1 283.2 306.4 270.6 308.5 256.3 304.4 280.4 287.5 325.2 330.2 306.8 263.7 284.8 316.6 309.1 266.1 251.5 318.8 264.2 269.6 250.9 276.5 300.4 250.6 287.8 266.9 Day 49 274.7 338.0 292.7 252.3 272.8 261.3 266.3 285.7 307.0 297.1 264.4 274.7 294.6 239.3 326.5 286.1 262.2 339.8 270.1 288.6 320.1 274.9 314.8 273.7 315.4 232.2 AK 294.8 336.7 333.2 311.8 269.2 297.3 317.1 315.5 283.6 259.9 287.3 219.7 272.0 258.3 289.9 313.1 257.1 305.0 269.6 599 Company Sanitized. Does not contain T H-24516: Subchronic Toxicity 90-Day Gavage Study in Rats with One-Generation Reproduction Evaluations Day 63 Day 70 Day 74 Female, VIII - 250 ing/kg/day 643341 643370 643446 643435 643466 643332 643404 643408 643359 643340 643487 643356 643329 643388 643450 643467 643443 643417 643413 643338 643335 643468 643440 643430 643431 643368 643326 643365 643375 643328 643348 643346 643449 643429 643424 643347 643456 643423 643345 643351 643358 643444 643474 643441 643481 283 .2 308 .7 307 .5 251 .8 280 .2 246 .8 26B .6 272 .0 317 .7 274 .4 265 .1 287 .2 290 .1 235 .9 334 .5 275 .8 260 .3 323 .0 276 .1 295 .1 313 .1 267 .2 240 .7 269 .8 328 .3 251 .4 332 .5 332 .0 279 .3 249 .8 310 .3 324.1 305 .6 279 .2 265 .8 306 .1 249 .6 268 .3 210 .5 288 .1 270 .3 254 .3 263 .5 271 .8 285 .9 297 .0 307 .5 250 .0 291 .0 268 .7 274 .4 284 .0 325 .5 FD TEST DAY 69 252 .3 292 .4 291 .1 247 .5 342 .4 231 .5 255.4 320 .5 279 .0 292 .5 298 .3 204 .8 195 .7 229 .9 281 .5 297 .8 324 .5 325 .9 288 .7 261 .0 315 .7 332 .2 279 .8 263 .7 263 .7 324.2 248 .7 268 .2 262 .0 287 .1 262 .8 261 .6 299 .5 274 .2 214 .9 229 .0 326 .6 283 .5 289 .5 283 .0 261 .7 269 .0 278 .6 325 .4 310 .2 331 .4 297 .6 267 .5 232 .5 316 .9 326 .0 297 .9 221 .0 INDIVIDUAL BODY WEIGHTS (g) Day 77 Day 84 Day 91 269. 9 289.4 301. 9 257. 0 275. 9 264. 2 262. 7 285. 1 328. 9 230. 7 287. 0 256. 0 244. 0 285. 8 299 .5 331 .1 313 .6 257 .8 288 .9 279.4 278 .1 302 .7 339 .7 272 .7 308 .7 300 .2 264 .3 330 .1 299 .0 348 .6 296 .9 254 .5 297 .6 277.4 268 .3 302 .8 349 .8 274 .0 312 .3 308 .7 261 .5 347 .9 265. 2 319.4 250. 2 262.2 276. 3 290. 8 283. 4 238. 9 307. 7 255. 5 268 .1 345 .7 279 .1 290 .0 275 .6 309 .7 311.7 267 .9 328 .2 274 .3 276 .7 337 .1 283 .5 280 .5 280 .0 323 .1 313 .9 269.3 336 .0 285 .9 Day 98 276.1 298.7 317.6 272.7 369.5 275.1 329.2 288.9 296.9 283.3 333.1 303.2 280.2 350.7 296.3 Day 105 280.6 298.7 324.0 271.5 384.6 275 .2 335 .1 297.0 307 .9 292 .1 350 .1 307 .9 275 .1 354.2 301 .9 600 Company Sanitized. Does not cont H-24516: Subchronic Toxicity 90-Day Gavage Study in Rats with One-Generation Reproduction Evaluations Day 119 Day 126 Female, 643341 643370 643446 643435 643466 643332 643404 643408 643359 643340 643487 643356 643329 643388 643450 643467 643443 643417 643413 643338 643335 643468 643440 643430 643431 643368 643326 643365 643375 643328 643348 643346 643449 643429 643424 643347 643456 643423 643345 643351 643358 643444 643474 643441 643481 VIII 250 286 .2 308 .6 325 .5 283 .6 404 .8 277.7 340.7 309.7 328.5 301.5 372.2 323.0 280.1 382.3 313.6 nig/kg/day 280 .8 310.4 331 .7 290 .9 411 .1 Day 133 288 .9 331 .5 343 .4 289 .1 416 .6 INDIVIDUAL BODY WEIGHTS (g) Day 140 Day 147 Day 154 292 .1 348 .6 335 .9 291 .3 422 .0 305 .5 365 .2 348 .0 296 .9 431 .4 318 .0 373 .2 357 .9 297 .0 437 .3 Day 161 316 .4 384 .4 364 .6 302 .4 442 .6 Day 168 316 .7 363 .1 373 .9 297 .6 444 .5 601 Company Sanitized. Does not conta H-24516: Subchronic Toxicity 90-Day Gavage Study in Rats with One-Generation Reproduction Evaluations Day 181 Female, 643341 643370 643446 643435 643466 643332 643404 643408 643359 643340 643487 643356 643329 643388 643450 643467 643443 643417 643413 643338 643335 643468 643440 643430 643431 643368 643326 643365 643375 643328 643348 643346 643449 643429 643424 643347 643456 643423 643345 643351 643358 643444 643474 643441 643481 VIII - 250 mg/kg/day 312.0 341.1 368.9 286.1 429.7 INDIVIDUAL BODY WEIGHTS (g) 602 Company 'Sanitised. Doss iwt cont H-24516: Subchronic Toxicity 90-Day Gavage Study in Rats with One-Generation Reproduction Evaluations______ DuPont-5386 __ APPENDIX D INDIVIDUAL FOOD CONSUMPTION 603 Company Sanitized. Daes rol certain TSCA CBI INDIVIDUAL FOOD CONSUMPTION EXPLANATORY NOTES Critical Dates Day 74 Male and female rats designated for reproduction evaluations were co-housed. Last day of food consumption data collection for rats designated for reproduction evaluation. Day 83-89 Rats designated for the 3-month recovery period were temporarily housed in metabolism cages for urine and feces collection. Food consumption data was not collected for these animals during this period. Day 91 Male rats designated for the 90-day exposure period were sacrificed. Day 93 Female rats designated for 90-day exposure period were sacrificed. Day 119 Last day of food consumption data collection for animals designated for the one-month recovery period. Day 125 Male and female rats designated for the one-month recovery period were sacrificed Day 175 Last day of food consumption data collection for animals designated for the 3-month recovery period. Day 181 Male and female rats designated for 3-month recovery period were sacrificed. Abbreviations AK Accidentally Killed FD Found Dead SB Sacrificed in extremis 604 Company Sanitized. Does not eontain TSCA CBS H-24516: Subchronic Toxicity 90-Day Gavage Study in Rats with One-Generation Reproduction Evaluations INDIVIDUAL FOOD CONSUMPTION (g/day) Day 7 Day 14 Male, I - 0 mg/kg/day 643241 643300 643143 643205 643235 643288 643150 643189 643185 643210 643268 643232 643265 643239 643270 643148 643284 643229 643196 643176 643218 643207 643280 643271 643211 643163 643197 643242 643251 643155 643147 643276 643237 643226 643195 643246 643253 643262 643172 643303 643304 643162 643254 643145 643204 28.6 25.0 25.4 25.8 29.3 26.5 25.0 29.4 27.7 23.8 25.3 24.0 24.1 28.4 24.3 23.3 26.8 22.9 22.4 23.6 26.0 22.7 24.7 28.6 26.3 29.7 26.5 26.S 25.2 24.4 28.4 29.7 21.5 23.8 25.2 30.0 26.6 24.3 27.3 26.5 23.0 25.3 24.4 23.2 27.7 31 .1 26.4 27 .7 25 .9 30 .4 28 .6 27 .4 33 .6 29 .4 25 .4 27 .2 22 .1 27.2 29 .1 27 .0 25 .8 27 .7 22 .6 23 .8 25 .7 25 .3 24 .1 27.2 31 .8 27 .9 32 .6 27 .7 26 .1 26 .6 25 .8 31 .8 33 .2 23 .0 23 .5 27 .0 32 .9 29 .1 27 .7 30.4 28 .3 25 .5 27 .0 23 .5 24 .6 28 .2 28.7 27.4 27.0 29.1 32.5 30.5 25.2 32.2 31.7 25.3 29.9 25.7 30.5 31.5 28.8 26.2 29.0 24.7 23.9 27.4 27.0 25.0 27.8 30.6 28.8 33.2 29.0 29.4 27.7 28.9 31.4 32.0 24.9 22.7 25.7 31.8 30.4 28.5 31.7 29.6 25.7 28.2 24.6 26.3 27.4 31.4 27.0 28.8 29.6 33.0 31.2 24.6 31.7 31.2 26.9 30.0 22.2 29.0 30.6 27.6 26.5 30.9 24.1 23.2 28.0 26.9 24.8 28.4 31.7 30.5 32.1 28.7 28.3 26.4 27.0 32.0 32.4 25.3 24.0 25.1 31.0 29.4 27.1 29.4 29.9 24.9 27.4 24.2 25.5 30.3 31.3 29.2 28.4 29.0 33.6 32.1 25.5 30.9 30.5 25.8 32.3 26.4 29.3 29.5 27.7 26.4 30.3 23-. 9 23.8 28.2 27.3 25.1 29.2 30.4 29.9 32.8 27.3 28.1 25.2 25.3 30.8 31.9 23.9 23.8 25.2 31.6 28.7 29.2 29.6 32.7 27.2 28.1 27.3 29.2 29.8 31 .5 30 .1 27 .4 30 .3 34 .6 31 .2 24 .9 31 .7 31 .6 26 .5 29 .8 27 .1 29 .9 31 .1 29 .2 27 .5 30 .0 24 .2 25 .8 29 .3 27 .0 24 .8 30 .1 33 .1 27 .5 31 .6 27.4 28 .6 24 .8 27 .3 31 .3 32 .4 24 .9 25 .2 27.2 31 .4 29 .6 27 .7 29 .0 33 .2 28 .0 24.4 25 .3 27 .2 29 .9 29.2 26.5 26.8 28.4 30.1 27.1 25.4 28.8 30.0 28.3 30.4 28.7 30.7 32.8 29.0 29.1 32.0 23.8 24.5 27.7 28.2 25.5 31.2 34.8 31.1 34.3 29.2 31.6 27.6 30.4 31.2 35.9 25.9 27.3 27.7 31.9 30.1 30.1 29.6 32.2 27.2 26.9 26.8 29.4 27.8 31 .2 32 .0 28 .6 30 .8 34.6 31 .6 26 .8 33.2 34 .2 25 .1 30 .9 27 .6 30 .0 30 .2 27 .3 27 .6 29 .6 23 .0 25 .1 26 .3 28 .3 24 .0 29 .3 33 .5 30 .0 34 .3 29 .3 30 .6 26 .5 31 .2 31 .2 35.2 25 .5 26.5 29 .5 30 .3 29 .9. 28 .7 31 .2 30 .7 27 .0 24 .0 26 .2 27 .6 28 .8 33.3 33.1 29.4 28.5 37.4 31.3 27.5 34.3 33.8 24.7 23.0 26.6 24.0 31.3 26.5 26.6 29.8 22.8 25.6 28.6 28.5 24.2 29. 35.0 29.2 34.3 28.8 30. 26. 31.0 30. 35. 26. 27. 28. 33. 30. 29. 30. 30. 28. 12. 26. 26. 29. Company Sanitized. Doss not con H-24516: Subchronic Toxicity 90-Day Gavage Study in Rats with One-Generation Reproduction Evaluations Day 74 Day 77 Male, I - 0 mg/kg/day 643241 643300 643143 643205 643235 643288 643150 643189 64318S 643210 643268 643232 643265 643239 643270 643148 643284 643229 643196 643176 643218 643207 643280 643271 643211 643163 643197 643242 643251 643155 643147 643276 643237 643226 643195 643246 643253 643262 643172 643303 643304 643162 643254 643145 643204 34.0 28.7 30.9 32.2 26.0 26.1 27.7 30.6 27.0 31.2 33.4 28.5 35.6 30.6 32.5 30.1 38.5 33.1 40.3 24.7 30.2 28.6 27.3 30.7 32.5 29.7 25.9 34.2 32.8 27.3 25.2 30.3 26.4 26 .4 28 .0 28 .0 30 .4 32 .8 23 .5 30 .1 28 .4 26 .3 17 .3 25 .0 27 .7 Day 84 29.0 29.0 27.0 30.7 33.6 29.7 26.3 32.5 32.2 26.7 27.9 30.4 25.9 24.2 26.6 27.8 30.1 32.0 24.9 28.1 28.4 26.9 15.9 24.9 30.4 INDIVIDUAL FOOD CONSUMPTION (g/day) Day 90 Day 98 Day 105 Day 112 28.5 27.5 25.2 28.3 33.1 25.1 25.5 32.7 31.5 22.9 21.2 27.8 24.6 26.9 31.1 27.9 26.4 27.4 31.0 29.0 27.3 23.6 31.0 27.6 26.0 23 .8 27 .2 28 .2 29.4 29 .2 25 .6 28.5 27 .6 24 .6 24 .2 25 .0 28 .8 24 .9 27.4 26 .3 33 .5 33 .1 28 .7 29 .1 30 .8 26 .8 25 .4 27 .0 24 .0 28 .2 28 .6 32 .6 31.6 31 .6 29.6 32 .6 28 .0 12 .4 26 .3 23 .5 27 .8 29 .9 31 .4 32 .5 31 .3 29 .0 32 .3 27.2 28 .2 28 .7 Day 119 28.6 17.1 25.8 24.6 23. 1 27. 4 29. 7 29. 5 32. 8 30. 8 27.3 30. 6 25. 4 14. 4 26. 1 Day 126 27. 28. 27. 26. 27. 606 Company Sanitized. Does not conta H-24516: Subchronic Toxicity 90-Day Gavage Study in Rats with One-Generation Reproduction Evaluations Day 140 Day 147 Male, I - 0 mg/kg/day 643241 643300 643143 643205 643235 643288 643150 643189 643185 643210 643268 643232 643265 643239 643270 643148 643284 643229 643196 643176 643218 643207 643280 643271 643211 643163 643197 643242 643251 643155 643147 643276 643237 643226 643195 643246 643253 643262 643172 643303 643304 643162 643254 643145 643204 28.3 33.1 29.3 21.3 27.7 29.2 30.7 30.2 26.0 13.9 Day 154 29.9 31.7 31.4 26.8 32.4 INDIVIDUAL FOOD CONSUMPTION (g/day) Day 161 Day 168 Day 175 Day 181 33.0 33.9 32.2 28.5 29.7 30.2 31.8 27.5 29.2 34.5 33.1 27.4 24.7 28.8 27.5 24.3 29.8 607 Company Sanitized. Does not co H-24516: Subchronic Toxicity 90-Day Gavage Study in Rats with One-Generation Reproduction Evaluations Day 7 Day 14 Male, III - 643173 643290 643272 643292 643228 643308 643264 643240 643180 643179 643202 643310 643306 643305 643293 643287 643188 643230 643170 643144 643277 643214 643261 643166 643153 643177 643198 643291 643184 643167 643223 643233 643183 643219 643263 25 mg/kg/day 29 .4 23 .2 23 .6 25 .6 23 .8 26 .7 27 .2 25 .0 25 .4 26 .4 24 .4 23 .2 23 .6 23 .5 24 .8 19 .1 29.3 24 .6 29 .8 22 .1 26 .5 28 .0 28 .9 24.4 23 .6 26 .3 30 .2 28 .2 27 .7 27 .0 26 .5 23 .0 27 .3 28 .7 26 .0 29 .9 24 .9 26.6 25 .6 30 .9 30 .9 29 .1 24 .9 28 .6 28 .1 25 .4 27 .9 24 .2 25 .6 26.4 21 .2 32 .4 25 .4 29 .6 24 .1 27 .8 29 .2 33 .7 27 .7 26 .7 28 .3 33 .2 31 .4 27 .7 29 .6 25 .6 23 .5 28 .7 28 .6 27 .0 Day 21 29 .3 26 .3 25 .6 27 .7 32 .3 31 .7 29 .3 23 .3 29 .2 29 .3 25 .4 31 .1 24 .1 25 .9 27 .2 21 .5 32 .8 25 .7 30.4 24 .2 29 .2 31 .1 33 .4 25 .8 26 .0 31 .8 34 .5 30 .3 26 .4 29 .8 25 .2 22 .9 28 .5 28 .0 27.4 INDIVIDUAL FOOD CONSUMPTION Day 28 Day 35 Day 42 (g/day) Day 49 29 .9 26 .6 26 .3 28 .6 32 .7 31 .2 29.1 23 .6 29 .4 28 .7 25 .0 30 .9 24 .9 25 .4 26.4 21 .6 32 .1 26 .7 30 .3 25 .5 30 .2 31 .9 31 .6 27 .6 27 .7 30 .1 35.4 32 .5 23 .7 29 .8 24 .6 22 .6 29 .2 28 .5 28 .0 32 .8 28 .4 26 .0 29 .8 35 .4 34 .0 31 .2 26 .0 32 .1 28 .7 26 .6 33 .3 27 .4 27 .1 30 .4 23 .9 31 .1 27 .0 32 .0 24 .3 30 .6 30 .8 32.2 27.4 28 .9 32 .7 34 .0 32 .0 19 .7 29 .8 26 .5 24.2 29 .5 29 .4 28 .6 29.0 29.0 37.2 29.2 33.6 34.9 31.7 24.4 32.4 28.1 25.5 33.4 28.1 25.4 28.4 22.9 31.6 25.3 31.1 25.2 30.8 29.0 32.3 25.5 26.0 30.3 32.5 30.8 27.7 29.3 27.0 23.2 31.2 29.3 28.3 27.4 25.3 24.8 26.1 30.0 29.5 28.6 23.4 27.8 25.6 27.7 30.1 22.0 26.7 29.5 22.9 32.7 25.7 30.4 25.3 31.2 13.2 33.2 28.4 25.2 31.0 35.2 31.9 25.0 29.1 27.8 23.832.1 29.5 28.9 Day 56 30.7 29.7 26.3 29.2 35.5 34.4 33.1 25.1 31.4 28.6 25.1 33.0 25.8 26.3 30.4 23.2 34.0 25.1 29.5 26.0 30.5 28.8 33.1 28.7 29.1 31.4 35.4 32.0 24.9 29.2 27.6 14.2 31.1 29.6 29.2 Day 63 29 . 28. 27 . 29 . 35 . 32 . 34 . 24 . 30 . 24 . 23 . 30 . 25 . 26 . 29 . 23 . 32 . 26 . 31. 25 . 31 . 29. 32 . 27 . 29 . 31 . 33 . 30 . 21 . 30 . 27 . 23 . 30 . 30 . 29 . 608 Company Sanitized. Does not con H-24516: Subchronic Toxicity 90-Day Gavage Study in Rats with One-Generation Reproduction Evaluations Day 74 Day 77 Male, III - 643173 643290 643272 643292 643228 643308 643264 643240 643180 643179 643202 643310 643306 643305 643293 643287 643188 643230 643170 643144 643277 643214 643261 643166 643153 643177 643198 643291 643184 643167 643223 643233 643183 643219 643263 25 ing/kg/day 22.3 33.9 25.8 29.7 25.0 31.1 33.3 32.1 30.3 29.7 29.9 36.2 32.8 33.6 32.0 28.8 27.0 31.1 30.9 27.8 29.3 28.9 27.4 24.6 33.0 33.4 30.8 22.1 25.6 26.3 24.2 29.8 22.9 25.3 27.0 Day 84 INDIVIDUAL FOOD CONSUMPTION (g/day) Day 90 Day 98 Day 105 Day 112 25.0 29.7 29.8 26.6 33.8 32.8 30.9 23.2 28.8 28.6 24.4 28.2 24.7 26.1 26.0 20.5 27.9 29.8 24.1 30.6 32.6 30.4 23.4 27.7 26.0 23.2 24.6 22.5 24.8 26.7 24.0 29.3 25.3 26.0 29.3 26 .2 31 .3 24 .4 28 .7 28 .0 26 .3 27 .0 25 .3 30 .3 29.7 Day 119 26 .2 27 .0 18.4 29 .0 28 .9 Day 126 25 . 27 . 25 . 26 . 26 . 609 Company Sanitized. Does no H-24516: Subchronic Toxicity 90-Day Gavage Study in Rats with One-Generation Reproduction Evaluations Day 140 Day 147 Male, III - 25 mg/kg/day 643173 643290 643272 643292 643228 643308 643264 643240 643180 643179 643202 643310 643306 643305 643293 643287 643188 643230 643170 643144 643277 643214 643261 643166 643153 643177 643198 643291 643184 643167 643223 643233 643183 643219 643263 25.0 30.6 26.9 31.4 29.6 26.7 31.7 27.7 31.4 30.2 Day 154 28.6 30.9 29.1 31.9 32.7 INDIVIDUAL FOOD CONSUMPTION (9/day) Day 161 Day 168 Day 175 Day 181 27.1 29.7 26.9 29.2 31.2 26.9 30.6 27.5 29.7 31.3 27.5 30.2 26.3 30.0 30.9 23.1 27.4 23.0 25.8 25.2 610 Company Sanitized. Does not con H-24516: Subchronic Toxicity 90-Day Gavage Study in Rats with One-Generation Reproduction Evaluations Day 7 Day 14 Male, V - 100 mg/kg/day 643250 643243 643311 643318 643247 643175 643314 643275 643257 643224 643169 643159 643286 643181 643206 643313 643182 643146 643312 643199 643267 643216 643244 643245 643301 643200 643255 643157 643238 643227 643164 643154 643156 643208 643190 23. 8 25. 9 26. 8 26. 5 29. 5 25. 9 28. 9 28. 0 26. 1 24. 1 22.4 23.4 20. 8 24. 6 21. 6 23. 4 26. 3 27. 6 27. 6 29. 3 26.4 28. 4 24. 9 22. 5 28. 1 27. 8 26. 7 25. 8 28. 3 26. 9 27. 3 25. 5 28. 4 26. 3 28. 0 23 .1 30 .2 29.5 27 .7 32 .3 28 .0 30 .8 27 .8 26 .9 24 .5 25 .5 27 .1 21 .6 27 .9 22 .8 25 .1 30 .7 29 .2 28.2 31 .8 29 .1 32 .7 27 .5 24.4 29 .4 30.2 30 .0 28 .9 26 .4 30 .1 30 .3 27 .3 30 .0 27 .4 30 .0 Day 21 INDIVIDUAL Day 28 FOOD CONSUMPTION Day 35 Day 42 (g/day) Day 49 25.3 28.7 27.2 30.4 28.7 28.5 29.6 27.2 26.3 24.9 26.2 27.4 22.9 28.1 24.5 24.9 31.7 29.2 27.8 31.9 29.7 33.5 26.1 24.6 29.8 30.2 30.2 29.4 27.8 28.4 29.4 27.9 29.9 26.1 28.9 25. 8 28. 0 28. 1 29. 6 29. 7 29. 7 28. 8 28. 7 25. 4 26. 0 26. 8 28. 3 26. 1 28. 9 24. 0 26. 1 32. 8 30. 6 27. 8 35. 4 30. 3 33. 4 27. 8 24. 2 31. 2 30. 9 30. 9 32. 3 28. 5 30. 1 31. 5 28. 3 31. 6 25. 9 29. 3 24 .4 31 .3 29 .5 29 .6 58 .6 29 .8 29 .0 28.6 27 .3 24 .8 27 .0 30.6 27 .3 29.4 24 .1 26 .5 32 .8 30 .8 28 .1 33 .0 31.3 33 .6 28 .2 24 .8 31 .5 29 .1 30 .0 30 .6 28 .6 28 .5 31 .1 27 .9 32 .8 27 .7 30 .9 22 .9 30 .0 30 .1 29 .1 31 .8 30.2 31 .0 28 .4 27 .6 25 .1 26 .4 29 .1 26 .6 31 .6 23 .8 27 .4 31 .7 30 .0 27 .8 32 .1 30 .4 33 .5 29 .4 23 .8 30 .0 30 .3 31 .1 30 .5 28 .0 29 .5 32 .6 27 .1 31.4 28 .5 30 .2 22.9 28.6 26.4 25.8 15.1 27.4 28.8 26.7 24.5 23.4 26.9 29.7 27.9 31.1 28.4 29.8 31.9 29.5 26.7 32.1 30.9 32.9 29.0 25.4 30.7 30.3 32.4 31.1 31.2 31.2 31.6 27.1 33.3 28.9 30.2 Day 56 24.5 30.8 27.6 28.8 27.1 31.8 30.8 30.8 26.6 26.1 26.9 29.9 26.8 31.4 25.3 27.0 32.2 30.4 28.5 31.0 30.7 33.9 27.1 25.3 31.4 31.6 31.3 31.0 30.5 30.2 30.6 26.0 34.5 29.8 31.6 Day 6 26 .2 30 .8 28 .8 29 .0 30 .7 27 .7 30 .8 31.3 25.6 26 .1 21 .4 28 .3 27 .6 27 .1 25 .4 29 .2 32 .5 30 .7 30 .3 29 .6 29 .5 31 .3 27 .2 27 .6 31 .9 31 .5 33 .7 32 .1 29 .2 35 .5 30 .6 26 .3 34 .1 28 .7 33 .1 611 Company Sanitized. Ooes no8 H-24516: Subchronic Toxicity 90-Day Gavage Study in Rats with One-Generation Reproduction Evaluations Day 74 Day 77 Male, v - 100 ing/kg/day 643250 643243 643311 643318 643247 643175 643314 643275 643257 643224 643169 643159 643286 643181 643206 643313 643182 643146 643312 643199 643267 643216 643244 643245 643301 643200 643255 643157 643238 643227 643164 643154 643156 643208 643190 25.7 32.1 28.2 28.5 28.8 30.6 29.8 23.5 22.8 30.4 35.5 32.3 29.5 29.6 34.6 20.8 28.5 29.1 30.6 26.4 23 .3 30 .2 26 .7 26 .5 28 .6 6 .8 32 .0 30 .1 24 .6 24 .0 26 .6 26 .9 25 .1 29 .7 24 .7 Day 84 INDIVIDUAL Day 90 FOOD CONSUMPTION Day 98 Day 105 (g/day) Day 112 23.4 27.3 27.0 25.0 27.9 AK TEST DAY 77 16.9 24.6 24.5 24.9 27.1 20.0 25.1 31.4 24.8 23 .6 27 .8 25 .8 25 .7 29 .7 26 .8 19 .5 23 .7 22 .5 28 .1 20 .5 23 .7 24 .9 23.4 31.1 26.5 21.8 23.0 24.6 29.9 1.4 24.6 31.2 24.7 27.7 18.5 23.7 32.9 22.2 Day 119 22.5 28.9 20.5 31.0 24.7 Day 12 29.1 30.1 15.3 29.4 23.6 612 Company Sanitized. Does not conta H-24516: Subchronic Toxicity 90-Day Gavage Study in Rats with One-Generation Reproduction Evaluations Day 140 Day 147 Male, V - 100 mg/kg/day 643250 643243 643311 643318 643247 643175 643314 643275 643257 643224 643169 643159 643286 643181 643206 643313 643182 643146 643312 643199 643267 643216 643244 643245 643301 643200 643255 643157 643238 643227 643164 643154 643156 643208 643190 27.7 13.7 32.5 33.5 26.7 30 .6 32 .3 31.4 36 .3 28 .1 Day 154 30 .3 33 .8 30 .0 35 .0 26 .9 INDIVIDUAL FOOD CONSUMPTION (g/day) Day 161 Day 168 Day 175 Day 181 29 .6 32 .5 28 .0 36.4 27 .8 30 .3 32 .2 27.6 40 .3 27 .8 28 .0 30 .3 30 .0 37 .8 27.2 24 .2 27 .5 26 .4 32 .1 24 .7 613 Company Sanitized. Does not contain TS H-24516: Subchronic Toxicity 90-Day Gavage Study in Rats with One-Generation Reproduction Evaluations 643194 643252 643260 643315 643215 643193 643298 643201 643259 643174 643283 643149 643178 643152 643295 643289 643171 643158 643249 643161 643309 643248 643285 643278 643299 643274 643192 643222 643160 643191 643203 643282 643302 643317 643225 643296 643258 643316 643220 643236 643165 643266 643151 643234 643281 Day 7 Day 14 250 m9/k9/day 26.4 25.9 25.4 23.6 26.6 26.6 26.7 28.3 25.1 30.8 23.8 24.9 23.1 29.0 24.2 23.4 30.7 29.5 25.8 25.6 32.5 27.7 25.0 25.2 26.4 24.7 28.4 28.3 28.0 26.4 26.1 29.2 24.7 25.9 27.5 29.8 24.7 24.7 25.6 26.6 25.4 28.1 20.9 35.7 20.5 25 .1 27 .5 26 .0 24 .0 27 .5 28 .8 29 .2 29 .8 27 .7 33 .0 26 .3 28 .1 25 .2 31 .1 26 .7 25 .8 33 .5 31 .9 27 .6 27 .7 34 .6 27 .1 27 .3 26 .5 28 .6 26 .9 29 .7 27 .4 27 .7 28 .6 29 .1 32 .8 27.4 29 .6 29 .3 31 .3 28 .6 29 .2 29 .7 28 .4 29.6 31 .6 22 .6 29 .9 27 .7 Day 21 INDIVIDUAL FOOD CONSUMPTION Day 28 Day 35 Day 42 (g/day) Day 49 25 .6 26 .6 25 .4 24 .9 26 .9 29 .4 27 .3 28 .7 28 .3 32 .3 24 .8 26 .9 24 .0 31 .7 27 .7 25 .7 33 .1 30 .5 24 .9 30 .5 33 .4 28 .8 26 .4 25 .7 27 .6 26 .9 30 .2 28 .4 29 .2 28 .0 29 .8 34 .7 27 .7 29 .8 28 .0 31 .5 28 .3 27 .8 27 .5 29 .1 27 .9 30 .0 21 .8 29 .9 26 .2 25.6 29.1 27.2 27.5 28.5 28.9 27.3 29.5 29.2 32.4 25.6 30.0 9.1 32.6 27.8 26.8 33.6 30.3 27.4 30.6 32.0 30.3 29.3 26.3 27.6 27.0 29.7 28.8 30.0 26.3 30.6 34.2 27.3 30.7 29.0 32.4 27.6 28.9 26.6 29.8 28.7 31.5 24.4 30.6 28.1 25.1 30.4 26.0 26.0 27.7 27.6 27.5 29.7 30.2 34.1 25.3 31.6 20.7 33.2 29.5 27.8 35.5 31.0 31.5 31.7 33.2 31.4 29.5 28.4 28.4 29.7 30.2 29.2 30.6 27.2 30.3 33.5 26.3 28.8 29.2 31.0 27.2 28.6 26.0 27.8 28.6 32.1 23.6 31.3 28.1 25 .0 29 .0 26 .8 26 .0 27 .5 29 .6 27 .1 30 .3 30 .1 35 .1 24 .0 32 .5 25 .5 32 .9 29 .7 27 .6 34 .9 31 .9 30 .7 28 .8 31 .3 30 .7 28 .5 26 .8 28 .3 28 .0 31 .7 29 .5 30 .2 26 .8 29 .1 33 .2 26 .5 29 .0 27 .3 29.5 12 .7 27 .6 25 .9 27 .6 27 .6 28 .7 22 .4 28 .8 28 .1 24 .8 19 .3 22 .6 21 .1 23 .2 24 .7 24 .2 22 .8 23 .4 26 .5 21 .6 28 .9 20 .8 32 .5 26 .9 25 .6 29 .1 32 .4 28.2 29 .0 29 .6 27 .0 27 .2 22 .6 25 .9 26 .0 28 .0 28 .0 30.7 27.2 27 .1 31 .8 25 .8 26 .1 24 .7 30 .4 24 .5 27 .5 24 .5 26 .4 19 .8 30 .0 23 .0 28 .8 26 .8 27 .5 23 .9 24 .5 22 .8 26.4 9 .9 28 .0 26 .5 23 .1 31 .0 24 .3 29 .2 24 .5 31 .3 12 .5 13 .6 32 .5 32 .4 29 .5 27 .4 18 .4 27 .6 26 .8 29.5 28 .2 24 .7 27 .0 29.2 30 .1 25 .2 27 .3 29 .1 25 .1 26 .1 26.2 30 .9 28 .0 28 .0 21 .8 30 .0 23 .9 28 .7 23 .7 26 .0 28 .7 27.0 30.2 25.2 26.4 25.3 23.2 27.9 29.3 22.6 33.4 19.9 23.2 23.4 27.4 14.5 23.5 31.6 29.2 25.3 17.4 28.9 15.8 24.9 21.0 22.9 24.3 19.8 22.5 28.3 25.8 27.5 26.2 19.1 20.6 29.8 28.3 27.1 27.3 18.2 22.2 21.3 27.9 20.7 16.8 28.0 614 Company Sanitized. Does not contai H-24516: Subchronic Toxicity 90-Day Gavage Study in Rats with One-Generation Reproduction Evaluations Day 74 Day 77 Male, VII - 250 mg/kg/day 643194 643252 643260 643315 643215 643193 643298 643201 643259 643174 643283 643149 643178 643152 643295 643289 643171 643158 643249 643161 643309 643248 643285 643278 643299 643274 643192 643222 643160 643191 643203 643282 643302 643317 643225 643296 643258 643316 643220 643236 643165 643266 643151 643234 643281 28.8 25.4 25.9 22.8 31.8 21.0 20.0 30.8 18.9 28.8 29.1 28.5 18.6 27.9 28.8 10.1 34.3 27.4 26.7 18.7 AK TEST DAY 70 27.8 25.3 31.6 15.5 13.5 27.6 27.7 23.2 26.7 16.9 36.4 25.3 37.4 27.3 26 .2 30 .2 11 .6 25 .6 26 .9 22 .3 10.4 23 .8 13 .9 28 .0 Day 84 INDIVIDUAL FOOD CONSUMPTION Day 90 Day 98 Day 105 (g/day) Day 112 26.9 29.5 24.7 26.9 29.1 28.5 27.0 29.0 26.7 27.4 23.0 25.8 20.8 31.4 22.0 27.4 29.9 24.1 21.0 28.8 27.8 23.9 26.7 26.1 27.8 24.5 20.5 18.8 26.4 24.3 24 .2 25 .5 20 .7 30 .3 23 .4 25 .4 23 .3 19 .4 31 .5 25 .0 18 .9 24 .0 19 .6 31 .7 23 .9 26 .6 32 .4 27 .2 26 .1 22 .9 31 .0 31 .7 26 .5 18 .1 29.6 26 .0 31 .3 26 .9 24 .0 22 .6 29 .5 30 .0 27 .4 20 .1 17 .5 26 .3 30 .3 25 .1 26 .5 22 .5 23 .5 27 .2 27 .5 21 .1 26 .7 27 .4 31 .3 26 .6 29 .9 21 .0 25 .5 25 .3 25 .1 21 .9 25 .8 26 .7 30 .5 23 .5 27 .8 21 .6 27 .7 24 .8 25 .7 20 .4 23 .1 Day 119 20 .5 24 .7 19 .5 32.4 22 .9 26. 8 29. 5 23. 7 27. 3 24. 6 24. 6 26. 7 27. 8 23. 6 25. 8 Day 126 23 .1 26 .2 20 .7 31.5 24 .2 615 Company Sanitized. Does not conta H-24516: Subchronic Toxicity 90-Day Gavage Study in Rats with One-Generation Reproduction Evaluations Day 140 Day 147 Male, VII - 643194 643252 643260 643315 643215 643193 643298 643201 643259 643174 643283 643149 643178 643152 643295 643289 643171 643158 643249 643161 643309 643248 643285 643278 643299 643274 643192 643222 643160 643191 643203 643282 643302 643317 643225 643296 643258 643316 643220 643236 643165 643266 643151 643234 643281 250 mg/kg/day 27 .0 28 .8 24 .6 29 .9 24 .3 28. 9 31. 0 24. 1 31. 0 28. 8 Day 154 30 .5 30 .5 24 .6 32 .4 29 .4 INDIVIDUAL POOD CONSUMPTION (g/day) Day 161 Day 168 Day 175 Day 181 30 .6 30 .5 25 .4 35 .9 31 .0 31.6 31.5 25.7 34.9 30.7 29 .2 29.9 23 .7 33 .1 28 .5 25 .9 25 .8 20 .8 31 .1 22 .8 616 Company Sanitized. Does not co H-24516: Subchronic Toxicity 90-Day Gavage Study in Rats with One-Generation Reproduction Evaluations Day 21 INDIVIDUAL FOOD CONSUMPTION Day 28 Day 35 Day 42 (g/day) Day 49 643477 643374 643406 6434B6 643361 643463 643398 643436 643362 643354 643402 643383 643465 643484 643384 643352 643343 643459 643394 643480 643319 643350 643363 643397 643421 643420 643419 643414 643401 643455 643378 643393 643447 643478 643386 643405 643425 643448 643426 643415 643453 643330 643336 643387 643377 18 .9 19 .8 17 .0 14 .8 18 .3 18 .9 16 .4 18 .7 18 .9 15 .9 15 .4 17.5 17.2 16 .8 16 .6 18 .7 17 .3 17 .7 20 .2 18 .6 18 .5 17 .3 20 .0 17 .5 18 .1 19 .8 22 .2 19 .8 14 .6 17 .7 21 .2 20 .7 18 .9- 18 .4 18 .5 22 .0 20 .1 22 .6 19 .1 21 .8 19 .3 21 .4 18 .8 19.2 18 .8 18 .5 19 .6 17 .7 13.4 18 .9 20 .7 18 .2 18 .9 19 .8 16 .5 20 .5 17 .1 20 .7 16 .9 19 .0 20 .7 19 .8 20 .2 20 .6 21 .4 19 .5 18 .0 22 .0 22 .0 19.4 22 .1 23.4 22 .7 17 .8 18 .8 23 .5 22 .8 20 .9 19 .7 19 .1 24 .7 22 .0 20 .9 19 .9 24 .0 22 .2 18 .7 21 .6 19 .9 18 .9 19 .8 18 .3 17 .2 15 .8 22 .3 21 .0 18 .0 18 .6 20 .5 18 .4 19 .0 18 .9 20 .2 17 .9 17 .8 21 .0 19.5 18 .8 19 .4 20 .8 20 .9 12 .8 20 .6 20 .7 18 .8 24 .7 24 .2 21 .8 16 .7 18 .9 22.2 22 .5 19 .5 18 .9 17 .7 22 .9 21 .1 19 .6 20 .9 22.4 21.4 19 .5 22 .1 21 .2 19 .8 18 .8 18 .0 19 .0 14 .4 20 .1 20 .8 18 .1 22 .3 19.2 16 .7 20 .3 16 .6 19 .2 15 .3 17 .7 20 .7 19 .1 19 .4 18 .7 20 .0 21 .0 17 .5 22 .6 19 .3 17 .4 22 .2 22 .3 19 .7 18 .0 18.2 20 .6 24 .6 20 .3 16 .5 17 .1 23 .9 21 .1 19 .5 20 .2 24 .2 21 .0 18 .8 22 .2 22.4 19 .8 21.9 18.5 19.1 15.9 21.5 21.7 20.9 21.3 20.9 17.8 22.2 19.8 20.3 17.9 21.4 22.2 22.3 21.5 21.0 21.7 22.9 18.6 22.7 19.4 18.8 27.6 25.7 22.5 17.9 17.7 22.3 23.4 22.0 17.4 17.4 24.7 19.5 20.7 22.1 22.1 21.8 21.3 21.8 23.4 21.2 20.4 21.9 18.4 17.0 19.8 19.9 18.2 18.4 22.0 19.4 23.0 20.4 19.9 15.6 17.1 20.3 19.8 22.8 18.7 19.7 21.0 18.9 21.4 20.0 20.5 25.9 24.8 22.5 16.9 18.9 21.3 22.6 21.8 17.6 17.5 24.7 21.5 20.8 20.0 21.4 21.1 19.3 21.1 23.1 20.3 18.5 18.2 18.0 16.7 26.1 19.4 18.8 17.6 19.1 20.4 25.2 22.6 21.7 18.1 19.3 21.1 21.1 22.1 21.1 20.7 20.9 18.8 21.9 21.3 18.8 27.2 24.9 23.3 19.3 18.2 22.6 22.7 21.2 18.4 18.5 24.1 20.2 19.7 20.2 20.7 20.8 19.2 21.2 24.0 20.3 18 .8 20 .1 19 .8 20 .5 24 .4 23 .8 22 .1 21.4 21 .5 21 .2 23 .1 24 .4 22 .0 16 .9 18 .8 20 .0 20 .5 19 .6 17 .0 20 .7 21 .9 20 .5 24 .7 19 .1 20 .3 24 .2 23 .9 22 .7 19 .9 18 .0 20 .2 24 .0 21 .1 17.6 18 .5 24 .0 20 .6 22 .5 20 .6 21 .6 20 .5 19.6 20 .0 23 .5 21 .7 20.6 22.4 20.6 19.2 24.9 22.7 21.3 18.8 21.9 20.9 20.8 21.9 20.9 17.2 19.8 20.3 16.8 20.1 19.8 20.0 20.6 20.4 22.8 19.0 19.0 24.9 23.3 23.5 18.2 19.2 21.9 22.0 22.7 18.3 19.0 22.0 21.3 23.8 21.3 26.3 21.0 19.9 21.2 22.8 22.8 617 Company Sanitized. Does not contain T H-24516: Subchronic Toxicity 90-Day Gavage Study in Rats with One-Generation Reproduction Evaluations Day 74 Day 77 Female, II - 0 nig/kg/day 643477 643374 643406 643486 643361 643463 643398 643436 643362 643354 643402 643383 643465 643484 643384 643352 643343 643459 643394 643480 643319 643350 643363 643397 643421 643420 643419 643414 643401 643455 643378 643393 643447 643478 643386 643405 643425 643448 643426 643415 643453 643330 643336 643387 643377 23.4 19.2 21.4 19.0 23.3 22.5 19.8 22.1 23.2 20.5 24.4 24.5 23.9 21.1 19.4 24.5 23.3 23.5' .19.8 19.2 17.7 24.2 18.6 16.6 25.0 23.1 23.2 21.0 21.0 20.2 20.5 25.5 20.9 19.0 19.5 20 .8 20 .8 20 .7 21 .5 27 .8 18 .7 19 .2 18 .7 22 .3 21 .7 Day 84 INDIVIDUAL FOOD CONSUMPTION Day 91 Day 98 Day 105 (g/day) Day 112 Day 119 19.2 20.2 33.5 16.2 24.9 21.3 22.7 21.8 20.7 19.9 21.7 21.1 21.2 16.0 18.6 20.0 22.2 18.5 13.3 24.4 19.7 20.4 21.9 19.3 19.9 20.3 20.3 18.5 16.4 16.6 21 .0 17 .7 21 .1 16 .2 18 .7 20 .4 10.7 20 .5 18 .1 17 .5 21 .0 18 .9 17 .5 17 .3 18 .4 20.8 19.9 16.5 17.2 15.9 21 .0 19 .8 22 .3 22 .5 29 .5 19 .9 19 .3 21 .6 20 .3 19 .3 21 .9 18 .6 17 .3 18 .5 25 .4 18 .5 7 .9 19.2 20.2 19 .7 21.4 19.4 25.2 19.6 27.1 21.1 14.2 20.3 22.7 20.1 21 .9 23 .9 24 .3 22 .3 27 .0 20 .8 22 .9 15 .8 26 .8 23 .2 21. 5 25. 1 22. 7 23. 1 27. 8 21. 3 22. 5 22 .5 24 .9 21 .2 24 .1 27 .0 22 .3 21.2 SE TEST DAY 105 22. 5 22. 6 20 .9 25 .0 Day 126 21 .0 21 .3 19 .7 19.0 15 .9 618 Company Sanitized. Does not H-24516: Subchronic Toxicity 90-Day Gavage Study in Rats with One-Generation Reproduction Evaluations Day 140 Day 147 Female, II - 0 mg/kg/day 643477 643374 643406 643486 643361 643463 643398 643436 643362 643354 643402 643383 643465 643484 643384 643352 643343 643459 643394 643480 643319 643350 643363 643397 643421 643420 643419 643414 643401 643455 643378 643393 643447 643478 643386 643405 643425 643448 643426 643415 643453 643330 643336 643387 643377 21 .9 23 .1 18 .9 17 .9 18 .9 23 .2 23.7 21 .9 20 .7 19 .8 Day 154 24 .1 26 .9 24 .8 19 .7 20 .7 INDIVIDUAL POOD CONSUMPTION Day 161 Day 168 Day 175 (g/day) Day 181 25. 3 27. 1 23. 6 23. 0 21. 9 23 .2 27 .8 22 .8 19 .8 19 .0 22 .0 22 .2 21 .9 18 .7 19 .6 21 .3 19 .3 20 .6 15 .7 18 .7 619 Company Sanitized. Does not cont H-24516: Subchronic Toxicity 90-Day Gavage Study in Rats with One-Generation Reproduction Evaluations Day 7 Day 14 Female, IV - 25 ing/kg/day 643390 643396 643380 643433 643389 643410 643321 643324 643458 643364 643483 643411 643379 643391 643437 643399 643334 643464 643369 643490 643342 643438 643445 643418 643325 643479 643403 643376 643422 643452 643475 643372 643400 643395 643457 15 .8 20 .6 18 .6 19.3 19 .1 19 .1 15 .4 17.2 15 .9 16 .2 17 .6 AK TEST DAY O 19 .0 17 .1 16 .0 16 .8 15 .5 18 .7 17 .2 18 .4 20 .0 18 .0 21 .9 16 .9 22 .2 18 .6 18 .1 17 .6 21 .2 18 .8 22 .9 17 .7 17 .3 17 .7 39 .0 16 .4 22 .0 23 .1 20 .0 18 .4 18 .1 14 .7 17 .8 16 .3 17 .9 17 .1 20 .1 18 .3 17.4 20 .2 17 .4 19 .0 18 .7 20 .3 21 .7 18 .9 22 .0 17 .5 18 .7 20 .1 19 .6 18 .3 23 .2 21 .4 19 .9 20 .1 17 .3 19 .0 39 .6 Day 21 INDIVIDUAL Day 28 FOOD CONSUMPTION Day 35 Day 42 (g/day) Day 49 18 .0 23 .6 21.2 23 .8 18 .9 21 .5 18 .4 19 .4 17 .6 18 .7 17 .9 21 .7 18 .8 18 .7 19 .9 18 .8 19 .6 18 .7 20 .9 20.2 20 .7 23 .6 17 .5 22 .5 22 .0 21 .7 19 .0 24 .0 23 .5 19 .5 21 .3 18 .9 19 .9 40 .0 17 .5 20 .6 22 .3 23 .2 17 .9 21 .0 17 .0 19 .3 16 .8 18 .9 17 .2 20.2 18 .5 17 .9 19 .9 18 .0 20 .6 21 .1 21 .3 21 .4 22 .5 24 .6 19 .4 22.2 21 .8 18 .2 17 .9 24 .1 23.2 20 .0 19 .7 18 .5 17 .9 39 .9 18.6 20 .4 23.8 21 .5 23.1 22 .0 22.2 22 .7 20.0 21 .7 21.5 22 .8 SE TEST DAY 29 21.0 19.3 20.8 20.1 19 .9 18 .7 20 .6 19 .0 20.3 18.3 18.8 21.7 19.2 21.4 20.1 21.7 20.9 20.9 28.4 20.1 21.7 20.7 19.2 18.3 22.2 22.7 21.0 20.2 19.2 18.0 37.4 20 .5 21 .2 18 .9 20 .2 18 .4 22 .2 17 .8 22 .0 22 .1 23 .3 27 .8 19 .8 22 .8 21 .1 20 .9 18 .3 22 .9 21 .5 22 .7 20 .9 19 .1 18 .4 36 .7 19.5 20.4 23.0 19.7 19.3 21.7 21.7 18.0 18.0 19.6 22.0 19.6 18.1 20.5 17.6 20.2 21.9 21.4 20.9 19.3 26.1 20.7 24.7 22.0 22.5 18.5 24.2 21.8 23.1 8.3 20.1 18.2 38.6 Day 56 20.0 23.3 25.7 22.5 12.6 21.6 20.7 23.6 19.8 19.1 20.7 19.7 26.0 19.9 18.4 19.8 18.5 20.0 21.5 18.1 23.3 17.7 23.9 22.1 20.0 18.6 24.3 21.1 19.2 22.9 19.9 18.6 38.3 Day 6 21 .0 23 .7 23 .4 21 .7 17 .7 21 .7 21 .1 20.7 21 3 20 .5 22 .0 20 .4 19.6 18 .8 18 .7 20 .3 19 .0 20 .3 21 .8 18 .1 22 .6 19 .5 24 .7 23 .7 18 .9 18 .0 23 .0 22 .4 21 .9 21 .1 20 .9 19 .7 20 .3 620 Company Sanitized. Does not con H-24516: Subchronic Toxicity 90-Day Gavage Study in Rats with One-Generation Reproduction Evaluations Day 74 Day 77 Female, IV - 25 ing/kg/day 643390 643396 643380 643433 643389 643410 643321 643324 643458 643364 643411 643483 643379 643391 643437 643399 643334 643464 643369 643490 643342 643438 643445 643418 643325 643479 643403 643376 643422 643452 643475 643372 643400 643395 643457 21.1 19.8 19.6 21.0 21.0 23.0 18.4 21.9 20.3 24.9 25.5 8.8 19.8 25.9 22.6 26.8 22.5 21.9 21.5 20.0 20 .5 28 .5 22 .6 21 .2 18 .6 21 .1 22 .1 21 .5 20 .3 17 .9 19 .1 19 .7 18 .1 Day 84 20.0 29.1 24.4 21.6 16.4 20.4 21.6 19.6 20.3 19.5 18.9 30.0 18.5 INDIVIDUAL FOOD CONSUMPTION (g/day) Day 91 Day 98 Day 105 Day 112 17 .0 23 .8 21 .5 20 .0 16 .0 18 .8 19 .8 21 .6 18 .3 18 .2 17 .7 18 .6 15 .6 18.7 21.4 18.5 17.5 18.6 21.2 20.6 19.7 19.0 22.5 21.5 19.9 Day 119 19.8 22.0 20.9 18.8 Day 126 19.8 22.5 21.7 18.5 621 Company Sanitized. Does not c H-24516: Subchronic Toxicity 90-Day Gavage Study in Rats with One-Generation Reproduction Evaluations INDIVIDUAL FOOD CONSUMPTION (g/day) Day 140 Day 147 Female, IV - 25 mg/kg/day 643390 643396 643380 643433 643389 643410 643321 643324 643458 643364 643411 643483 643379 643391 643437 643399 643334 643464 643369 643490 643342 643438 643445 643418 643325 643479 643403 643376 643422 643452 643475 643372 643400 643395 643457 20.0 23.4 22.5 22.1 22.5 24.0 21.2 21.2 Day 154 22.2 24.4 23.6 22.1 Day 161 20.9 23.7 20.6 20.0 Day 168 20.8 23.6 22.0 20.5 Day 175 21.2 23.9 21.6 17.7 Day 181 16.7 20.3 18.4 17.4 622 Company SaiaiSSzeA Does H-24516: Subchronic Toxicity 90-Day Gavage Study in Rats with One-Generation Reproduction Evaluations Day 7 Day 14 Female, VI - 100 mg/kg/day 643322 643469 643409 643366 643367 643461 643462 643392 643472 643323 643412 643382 643381 643360 643373 643320 643488 643428 643439 643353 643385 643339 643473 643337 643416 643407 643357 643331 643427 643470 643434 643349 643454 643333 643460 18 .6 17 .5 16 .1 18 .9 18 .5 21 .7 17 .7 13 .5 16 .4 16 .9 17 .1 16 .0 17 .4 15 .1 17 .7 18 .3 18.6 20.4 17 .8 17 .8 17 .0 17 .9 18 .1 21.5 17 .9 17 .7 17 .8 17 .1 18 .5 18 .0 17 .9 18 .0 20 .3 18 .6 19 .7 18 .9 16 .7 17 .4 19 .1 19 .5 21 .7 18 .9 15 .5 16 .1 18 .1 18 .6 16 .5 17.4 16 .1 17 .2 19 .1 20 .0 21.5 19 .4 18.5 18 .9 19 .5 17 .3 20 .9 19 .9 19 .9 16 .7 17 .0 18 .3 20 .0 17 .7 18.5 19 .6 18 .1 19 .7 Day 21 19 .1 18 .9 17 .8 20 .0 20 .9 22 .2 19 .3 16 .0 16 .7 19 .8 20 .5 19 .8 19 .5 17 .7 20 .5 21 .2 22 .7 20 .2 19 .9 19 .3 19 .7 19 .0 19 .3 22 .9 21 .3 23 .7 17 .9 18 .4 20 .2 20 .4 19 .6 19 .4 20 .6 19 .8 20 .7 INDIVIDUAL FOOD CONSUMPTION (g/day) Day 28 Day 35 Day 42 Day 49 19.7 17.5 17.1 21.6 21.9 22.3 19.5 17.4 18.1 21.3 19.3 6.6 19.1 16.8 21.5 23.0 21.2 22.3 19.3 19.7 18.3 21.6 19.4 24.3 22.2 22.2 20.1 18.7 19.9 21.0 19.1 21.4 20.4 18.2 20.9 19.6 19.0 18.9 21.8 19.4 23.1 17.9 17.2 16.6 19.1 18.0 9.7 18.8 15.8 20.2 22.2 19.9 22.8 18.2 21.3 19.2 21.2 18.6 18.2 19.8 21.7 18.1 19.5 20.3 20.7 19.4 19.8 20.6 18.9 21.2 17. 9 17. 4 16. 7 21. 8 18. 8 20.2 18. 1 17.4 17. 6 20. 1 17. 0 10. 5 18. 5 17. 6 19. 1 21. 7 20. 1 20. 3 19. 3 20. 0 18. 5 20. 3 19. 3 7. 0 19.2 19. 1 19. 1 18. 6 18. 7 19. 9 18. 3 19. 0 21.4 17. 2 19. 8 16 .3 21.4 18 .1 19 .8 18 .6 16 .5 17 .0 14 .6 16 .5 17 .9 18 .9 17 .1 18 .9 19 .9 21 .8 22 .2 19 .8 21 .6 19.5 22 .9 19 .8 21 .7 19 .2 25 .2 21 .0 23 .4 20 .6 20 .2 19 .5 21 .9 22 .0 21 .6 24 .1 19 .0 22 .7 Day 56 19 .3 22 .7 17 .4 21 .9 22 .5 21 .9 18 .9 16 .9 19 .0 21 .0 21 .1 22 .7 19 .1 18 .7 19 .3 23 .3 20 .7 20 .0 18 .8 21 .1 19 .3 21 .6 19 .1 19 .9 21 .2 24 .2 20 .2 20 .9 19 .7 20 .3 19 .8 20 .2 23 .4 19 .3 21 .1 Day 63 20 .3 20 .6 19 .4 21 .8 19 .8 20 .4 19 .6 17 .0 18 .2 20 .8 20 .5 12 .1 17 .2 16.2 21 .3 20 .5 18 .7 20 .2 18 .0 21 .1 18 .0 23.4 18 .0 22.4 18 .9 20 .8 18 .1 20 .2 18 .0 22.4 17 .6 19 .8 21 .2 20 .0 20 .7 623 Company SaniSfeetl. Does not co H-24516: Subchronic Toxicity 90-Day Gavage Study in Rats with One-Generation Reproduction Evaluations Day 74 Day 77 Female, VI - 100 mg/kg/day 643322 643489 643409 643366 643367 643461 643462 643392 643472 643323 643412 643382 643381 643360 643373 643320 643488 643428 643439 643353 643385 643339 643473 643337 643416 643407 643357 643331 643427 643470 643434 643349 643454 643333 643460 21.0 20.9 18.9 17.6 21.2 21.1 23.8 19.2 9.8 19.1 22.3 20.5 21.2 19.2 24.2 21.4 20.3 22.2 20.2 20.9 18 .5 20 .5 18 .6 22 .7 19 .6 18 .4 17 .2 17 .8 17.4 20 .1 20 .8 16 .5 19 .5 16 .9 23 .9 Day 84 18 .2 19 .1 17 .3 20 .5 21 .5 15 .5 18 .9 17 .4 17 .3 19 .8 22.2 17 .9 19 .9 17 .7 20.4 INDIVIDUAL FOOD CONSUMPTION (g/day) Day 91 Day 98 Day 105 Day 112 16 .6 20 .9 16 .7 19 .3 21 .0 18 .8 17 .9 14 .5 15 .3 15 .4 17 .1 15 .7 17 .6 15 .0 18 .1 17 .7 18.2 17 .0 14 .2 18 .1 19 .3 15 .3 19 .5 17 .8 19 .3 20 .9 16.4 20 .2 10 .1 21 .8 Day 119 20 .9 7.4 20 .6 15 .5 20 .3 Day 126 20 .1 23.4 19 .5 16 .8 23.2 624 Company Sanitized. Does no8 contain T H-24516: Subchronic Toxicity 90-Day Gavage Study in Rats with One-Generation Reproduction Evaluations Day 140 Day 147 Female, VI - 100 ing/kg/day 643322 643489 643409 643366 643367 643461 643462 643392 643472 643323 643412 643382 643381 643360 643373 643320 643488 643428 643439 643353 643385 643339 643473 643337 643416 643407 643357 643331 643427 643470 643434 643349 643454 643333 643460 22 .6 30 .7 20 .0 18 .5 22 .2 22 .4 29 .3 23 .0 21 .0 26 .6 Day 154 21.0 18.4 23.6 20.4 23.2 INDIVIDUAL FOOD CONSUMPTION (g/day) Day 161 Day 168 Day 175 Day 181 22 .9 25 .6 21 .3 18.4 24 .9 22 .8 20 .5 21 .1 18 .0 24 .2 21 .7 18 .0 20 .7 18 .8 25 .8 18 .4 32 .5 19 .0 19 .2 23 .7 625 Company Sanitized. Does sol conta H-24516: Subchronic Toxicity 90-Day Gavage Study in Rats with One-Generation Reproduction Evaluations Day 7 Day 14 Female, 643341 643370 643446 643435 643466 643332 643404 643408 643359 643340 643487 643356 643329 643388 643450 643467 643443 643417 643413 643338 643335 643468 643440 643430 643431 643368 643326 643365 643375 643328 643348 643346 643449 643429 643424 643347 643456 643423 643345 643351 643358 643444 643474 643441 643481 VIII - 250 17.5 21.3 17.7 16.7 15.8 15.8 15.6 18.1 16.7 16.7 16.3 16.8 17.6 15.4 19.7 20.0 15.1 19.9 17.3 18.2 18.9 17.2 19.6 16.5 18.5 18.0 19.0 22.3 21.4 20.8 17.2 18.4 19.3 17.9 17.6 16.0 20.9 17.1 19.2 14.9 18.6 17.9 16.7 20.1 17.9 mg/kg/day 18. 2 22. 6 19. 1 20. 0 16. 9 18. 3 17. 9 20.4 19. 0 19. 7 17. 0 18. 2 18. 5 20. 9 18. 2 23. 3 21. 2 21. 1 18. 9 18. 6 20. 0 19. 0 21. 3 19. 0 19.2 18.4 19. 4 23. 3 22. 5 19. 8 18. 2 18. 8 22. 0 19. 7 18. 9 17. 7 20. 9 17. 6 18. 8 18. 3 18. 5 18. 5 17. 4 19. 2 18. 0 Day 21 19.0 25.9 20.3 19.1 19.1 18.1 18.3 20.3 19.0 19.3 17.8 19.0 18.1 19.6 23.2 20.6 17.0 20.4 19.5 19.6 22.5 22.3 25.4 22.0 21.6 19.7 22.4 26.2 23.9 22.4 22.1 22.0 24.4 21.9 21.4 16.2 23.3 17.8 21.6 19.4 22.1 21.5 17.8 20.9 21.5 INDIVIDUAL FOOD CONSUMPTION Day 28 Day 35 Day 42 (g/day) Day 49 17 .6 23 .3 19 .5 17 .7 20 .4 17 .9 20 .0 20 .4 21 .4 20 .3 17 .9 18 .5 20 .1 19 .9 21 .5 21 .5 17 .8 20 .6 19 .7 19 .2 21 .8 19 .0 21 .2 19 .4 19 .4 20 .2 20 .8 26 .8 25 .7 21 .9 20.4 18 .7 23 .0 20 .5 17 .9 17 .3 20 .5 18 .4 18 .5 18 .5 19 .4 20 .6 16 .4 18 .6 18 .7 18.9 24.3 19.2 17.2 19.2 20.3 20.5 19.9 20.9 21.6 17.7 17.8 22.3 19.6 23.3 22.9 18.6 19.7 19.6 19.5 23.2 19.3 22.1 20.6 21.5 19.0 21.6 26.6 25.1 24.2 20.5 20.3 22.9 21.8 21.1 17.9 22.9 17.7 20.2 18.2 18.4 21.2 17.8 19.7 19.3 18.0 23.8 17.4 18.2 20.1 18.8 17.9 20.7 18.7 19.8 17.4 14.9 22.4 19.7 21.6 22.7 16.6 20.4 18.7 19.3 21.6 17.9 20.2 18.8 22.1 19.1 19.2 24.2 24.6 20.1 19.5 18.4 20.1 20.4 18.7 16.7 21.0 16.5 20.7 16.2 17.7 22.5 17.5 20.2 19.9 17.6 23.1 17.7 16.6 17.4 15.3 16.8 20.3 20.0 21.3 16.1 17.2 23.6 14.5 21.3 21.0 18.3 21.6 20.3 20.3 22.5 19.2 19.8 20.8 22.0 10.2 19.1 25.8 22.7 21.6 18.4 20.2 21.4 20.5 22.2 18.4 15.6 6.8 16.9 18.1 18.9 22.9 17.3 19.8 19.0 Day 56 Day 63 18.5 19. 20.6 21.0 15. 19.0 17.5 18. 21.3 19.8 17.3 15.2 21.6 19.7 19.3 15. 21.5 22.3 24.5 18.7 19.5 12.4 15.8 32.8 20.2 22.4 2.5 23.8 19.4 21.6 21.3 15.4 18.2 16.2 22.7 17.7 20.1 19. 21.1 19. 23.2 19.0 17.3 14.6 16.1 21.5 6. 18.4 22.8 19. AK TEST DAY 53 19.8 26.8 24.6 17.0 12.8 25. 21. 13. 19.3 12. 22.2 21. 22.0 18. 19.2 18. 21.0 19. 18.9 18. 7.3 21. 12.3 20. 11.4 19. 17.5 10. 18.8 21. 24.7 11. 18.9 17. 16.1 10. 19.4 18. 626 Company SasigizA Does not H-24516: Subchronic Toxicity 90-Day Gavage Study in Rats with One-Generation Reproduction Evaluations Day 74 Day 77 Female, VXII - 250 mg/kg/day 643341 643370 643446 643435 643466 643332 643404 643408 643359 643340 643487 643356 643329 643388 643450 643467 643443 643417 643413 643338 643335 643468 643440 643430 643431 643368 643326 643365 643375 643328 643348 643346 643449 643429 643424 643347 643456 643423 643345 643351 643358 643444 643474 643441 643481 6.8 9.5 18.2 20.6 20.0 16.3 25.5 28.3 22.6 40.1 52.1 26.2 14.4 13.1 8.4 21.0 18.2 .20.6 4.0 15 .8 15.4 17 .8 17 .4 16 .3 16 .2 14 .8 18 .9 23 .6 12 .9 15 .5 10 .6 16 .8 5 .1 19 .1 20 .3 12 .2 17 .7 20 .9 19 .1 17 .4 13 .4 26 .3 14 .8 Day 84 21 .6 29 .2 20 .1 16 .9 19 .8 24 .6 25 .3 22 .9 23 .4 19 .7 22 .1 23 .1 20 .9 24 .3 21 .4 24 .2 23 .3 23 .3 17 .3 22 .1 29 .2 21 .3 25 .3 21 .3 INDIVIDUAL FOOD CONSUMPTION (g/day) Day 91 Day 98 Day 105 Day 112 18 .4 25 .7 14 .0 14 .1 16 .9 18 .5 15 .5 18 .9 24 .4 16 .6 17 .7 20 .4 17 .1 24 .3 16.9 15.6 19.9 17.6 26.9 17.0 14.8 21.1 17.1 27.2 16.8 14.8 17.4 20.1 25.8 18 .1 18 .1 18 .0 18 .0 16 .1 20 .7 20 .2 16 .8 23 .4 18 .1 24 .7 19 .1 18 .3 20 .7 16.4 21 .0 16 .7 16 .8 24 .3 20 .4 24 .2 18 .7 18 .5 21 .4 18 .8 23.1 20 .0 16.4 26 .2 20 .4 20.4 17.6 18.3 20.9 17.8 20.1 18.3 16.9 22.1 19.2 Day 119 16.9 16.4 18.6 18.5 24.0 12 .1 19 .1 19 .0 22 .9 17 .3 23 .0 21 .0 17 .3 22 .3 20 .2 Day 126 16. 17. 18. 18. 22. 627 Company Sanitized. Does n H-24516: Subchronic Toxicity 90-Day Gavage Study in Rats with One-Generation Reproduction Evaluations Day 140 Day 147 Female, VIZI - 250 mg/kg/day 643341 643370 643446 643435 643466 643332 643404 643408 643359 643340 643487 643356 643329 643388 643450 643467 643443 643417 643413 643338 643335 643468 643440 643430 643431 643368 643326 643365 643375 643328 643348 643346 643449 643429 643424 643347 643456 643423 643345 643351 643358 643444 643474 643441 643481 17 .4 24 .5 17 .1 21 .6 21 .3 19 .7 25.2 19 .9 22 .8 23 .7 Day 154 21 .3 25 .7 21 .5 20 .1 26 .0 INDIVIDUAL POOD CONSUMPTION (g/day) Day 161 Day 168 Day 175 Day 181 20 .1 26 .5 21 .1 21.3 23 .8 20 .4 22 .4 22 .6 20 .9 24 .9 19 .5 18 .4 22 .7 19 .3 23 .3 19 .0 19.4 18 .5 18 .3 22 .0 628 Company Sanitized. Does not co