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TRADE SECRET Study Title H-24516: Subchronic Toxicity 90-Day Gavage Study m Rats with One-Generation Reproduction Evaluations Volume 3 of 5 Laboratory Project ID: DuPont-5386 AR226-3199 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.I. du Pont de Nemours and Company Haskell Laboratory for Toxicology and Industrial Medicine Elkton Road, P.O. Box 50 Newark, Delaware 19714-0050 WORK REQUEST NUMBER:)fjy^ SERVICE CODE NUMBER: |f|9 9 SPONSOR STUDY NUMBER:mHB I Company Sanitized. Does not contain TSCA COT Page 629 of 1500 APPENDIX E INDIVIDUAL CLINICAL AND OPHTHALMOLOGICAL OBSERVATIONS AND MORTALITY DATA S. Does sgSe^i^ r^ ^ 630 H-24516: Subchronic Toxicity 90-Day Gavage Study in Rats with One-Generation Reproduction Evaluations______________DuPont-5386 INDIVIDUAL CLINICAL AND OPHTHALMOLOGICAL OBSERVATIONS AND MORTALITY DATA EXPLANATORY NOTES Critical Dates Day 74 Maig and female rats designated for reproduction evaluations were co-housed and are reported as "removed from study" in this appendix. Clinical Observations recorded during the cohabitation and post-mating periods are reported in the Reproductive Toxicology section. Day 80 Ophthalmology examinations were conducted on rats designated for the 90day exposure period and the one-month recovery period. Day 91 Male rats designated for the 90-day exposure period were sacrificed. Day 93 Female rats designated for the 90-day exposure period were sacrificed. Day 122 Ophthalmology examinations were conducted on rats designated for the onemonth recovery period. Day 125 Male and female rats designated for the one-month recovery period were sacrificed. Day 181 Male and female rats designated for the 3-month recovery period were sacrificed. Any clinical sign observed on consecutive data collection days is assumed to have been present during the interim between observation days, and will be reported as having been observed over the period from the first-last day observed. Ophthalmology Evaluation observations and Clinical Pathology Evaluations are documented as Clinical Observations and interrupt the continuing clinical observations. All ophthalmology observations from test days 80 or 122 are those observed during the examination by the veterinary ophthalmologist. OwBpanirSanlteed.Does nnie^M -re-^ ^ 631 H-24516: Subchronic Toxicity 90-Day Gavage Study in Rats with One-Generation Reproduction Evaluations Sex Group Animal M I 643241 M I 643300 M I 643143 M I 643205 M I 643235 M I 643288 M I 643150 M I 643189 M I 643185 INDIVIDUAL CLINICAL AND OPHTHALMOLOGICAL OBSERVATIONS AND MORTALITY DA Observation Days General observation, No Abnormality Detected Eye Observations, Bled via Orbital for Clin Path, Eye Observations, Bled via Orbital for Clin Path, No Ophthalmological Abnormalities Detected Sacrificed by design Bilateral Right General observation. No Abnormality Detected Eye Observations, Bled via Orbital for Clin Path, No Ophthalmological Abnormalities Detected Sacrificed by design Right General observation. No Abnormality Detected Eye Observations, Bled via Orbital for Clin Path, No Ophthalmological Abnormalities Detected Wound, Superficial, Shoulder, Right Sacrificed by design Right General observation. No Abnormality Detected Eye Observations, Bled via Orbital for Clin Path, No Ophthalmological Abnormalities Detected Sacrificed by design Right General observation, No Abnormality Detected Eye Observations, Bled via Orbital for Clin Path, No Ophthalmological Abnormalities Detected Sacrificed by design Right General observation, Mo Abnormality Detected Eye Observations, Bled via Orbital for Clin Path, No Ophthalmological Abnormalities Detected Sacrificed by design Right General observation. No Abnormality Detected Eye Observations, Bled via Orbital for Clin Path, No Ophthalmological Abnormalities Detected Sacrificed by design Right General observation. No Abnormality Detected Eye Observations, Bled via Orbital for Clin Path, Eye Observations, Bled via Orbital for Clin Path, No Ophthalmological Abnormalities Detected Sacrificed by design Bilateral Right 0-42,49-77,84-91 91 44 80 91 0-42,49-77,84-91 44,91 80 91 0-28 44,91 80 35-42,49-77,84-91 91 0-42,49-77,84-91 44,91 80 91 0-42,49-77,84-91 44,91 80 91 0-42,49-77,84-91 44,91 80 91 0-42,49-77.84-91 44,91 80 91 0-42,49-77,84-91 44 91 80 91 General observation, No Abnormality Detected Eye Observations, Bled via Orbital for Clin Path, Eye Observations, Bled via Orbital for Clin Path, No Ophthalmological Abnormalities Detected Sacrificed by design Bilateral Right 0-42,49-77,84-91 91 44 80 91 632 H-24516: Subchronic Toxicity 90-Day Gavage Study in Rats with One-Generation Reproduction Evaluations Sex Group Animal 643210 643268 643232 643265 INDIVIDUAL CLINICAL AMD OPHTHALMOLOGICAL OBSERVATIONS AND MORTALITY DA Observation Days General observation, No Abnormality Detected Eye Observations, Bled via Orbital for Clin Path, Bilateral Eye Observations, Bled via Orbital for Clin Path, Left Eye Observations, Bled via Orbital for Clin Path, Right Discharge, Eye right. Black Sacrificed by design 0,7,14-28,35-49,84,90,98,1 140-154,161-181 55,101 9,96,108,139,160,181 0-3,21,34,76,89,92,115,12 56-70,77,126-133 181 General observation, No Abnormality Detected Eye Observations, Bled via Orbital for Clin Path, Bilateral Eye Observations, Bled via Orbital for Clin Path, Left Eye Observations, Bled via Orbital for Clin Path, Right Discharge, Eye right. Black Sacrificed by design 0,7,14-28,35-49,63-70,112 161-181 34 9,55,76,89,92-96,101,108,1 0-3,21,115,125 56,77-84,90,98,105,119,12 181 Eye Observations, Bled via Orbital for Clin Path, Bilateral Eye Observations, Bled via Orbital for Clin Path, Left Eye Observations, Bled via Orbital for Clin Path, Right Hair Loss, Forepaw, Bilateral Feces, Present, Brown Sacrificed by design 3,9,21,101 55,96,139,160,181 0,34,76,89,92,108,115,125 0,7,14-28,35-49,56-70,7798,105,112,119,126-133,14 21 181 General observation. No Abnormality Detected Eye Observations, Partially Closed, Left Eye Observations, Enophthalmus, Left Eye Observations, Eye Observations, Eye Observations, no blood Eye Observations, bled by tail vein Eye Observations, Eye Observations, Eye Observations, Exophthalmus, Le ft Bled via Orbital for Clin Path, Bled via Orbital for Clin Path, Bled via Orbital for Clin Path, Bled via Orbital for Clin Path, Corneal Opacity, Bilateral Corneal Opacity, Left Bilateral Bilateral, Bilateral, Right Eye Observations, tail vein Discharge, Hose, Black Discharge, Eye left. Black Hair Loss, Face, Left Sacrificed by design 0,21-28,35-49 119,126-133,140-154,161-1 77-84,90,98,105,112,119,1 140-154,161-181 : 56-70 9,21,55 101 108,115,125 0-3,34,76,89,92-96,139,16 147-154,161-181 70,77-84,90,98,105,112,11 140 160 7,14 56-63 70 181 : 633 H-24516: Subchronic Toxicity 90-Day Gavage Study in Rats with One-Generation Reproduction Evaluations INDIVIDUAL CLINICAL AND OPHTHALMOLOGICAL OBSERVATIONS AND MORTALITY DAT Sex Group Animal Observation M I 643239 General observation, No Abnormality Detected Hair.Loss, Shoulder, Left Wound, Superficial, Shoulder, Left Removed from study M I 643270 General observation, No Abnormality Detected Removed from study M I 643148 General observation, No Abnormality Detected Removed from study M I 643284 General observation, No Abnormality Detected Removed from study M I 643229 General observation, No Abnormality Detected Removed from study M I 643196 General observation, No Abnormality Detected Removed from study M I 643176 General observation, No Abnormality Detected Removed from study a M I 643218 .General observation, No Abnormality Detected Removed from study n M I 643207 General observation, No Abnormality Detected Hair Loss, Forepaw, Bilateral ^ Removed from study tfl) BSl M I 643280 General observation, No Abnormality Detected 3RT. Removed from study & M I 643271 General observation, No Abnormality Detected 0 Removed from study 0 ra M I 643211 General observation, No Abnormality .Detected 68 Removed from study r M I 643163 General observation, No Abnormality Detected 0 Removed from study 3 p S, M I 643197 General observation, No Abnormality Detected 3' Removed from study "f (A 0 M I 643242 General observation, No Abnormality Detected 3&- Removed from study 0 05 Days 0,21-74 14 7 74 0-74 74 0-74 74 0-74 74 0-74 74 0-74 74 0-74 74 0-74 74 0-35 42-74 74 0-74 74 0-74 74 0-74 74 0-74 74 0-74 74 0-74 74 634 1-24516: Subchronic Toxicity 90-Day Gavage Study in Rats with One-Generation Reproduction Evaluations Sex Group Animal M I 643251 M I 643155 M I 643147 M I 643276 M I 643237 M I 643226 M I 643195 M I 643246 M I 643253 M I 643262 M I 643172 M I 643303 M I 643304 INDIVIDUAL CLINICAL AND OPHTHALMOLOGICAL OBSERVATIONS AND MORTALITY DAT Observation Days General observation. No Abnormality Detected Removed from study 0-74 74 General observation. No Abnormality Detected Removed from study 0-74 74 General observation. No Abnormality Detected Removed from study 0-74 74 General observation. No Abnormality Detected Removed from study 0-74 74 General observation. No Abnormality Detected Mo Ophthalmological Abnormalities Detected Sacrificed by design 0-77,84-119,125 80,122 125 General observation. No Abnormality Detected Mo Ophthalmological Abnormalities Detected Sacrificed by design 0-77,84-119,125 80,122 125 General observation. No Abnormality Detected No Ophthalmological Abnormalities Detected Sacrificed by design 0-77,84-119,125 80,122 125 General observation. No Abnormality Detected No Ophthalmological Abnormalities Detected Sacrificed by design 0-77,84-119.125 80,122 125 General observation. No Abnormality Detected No Ophthalmological Abnormalities Detected Sacrificed by design 0-77,84-119,125 80,122 125 General observation, No Abnormality Detected No Ophthalmological Abnormalities Detected Sacrificed by design 0-77,84-119,125 80,122 125 General observation. No Abnormality Detected No Ophthalmological Abnormalities Detected Sacrificed by design 0-77,84-119,125 80,122 125 General observation. No Abnormality Detected Hyperreactive No Ophthalmological Abnormalities Detected Sacrificed by design 0-77,84-112 119,125 80,122 125 General observation. No Abnormality Detected Mo Ophthalmological Abnormalities Detected Sacrificed by design 0-77,84-119,125 80,122 125 635 H-24516: Subchronic Toxicity 90-Day Gavage Study in Rats with One-Generation Reproduction Evaluations INDIVIDUAL CLINICAL AND OPHTHALMOLOGICAL OBSERVATIONS AND MORTALITY DAT Sex Group Animal M I 643162 M I M I 643254 643145 M I 643204 Observation General observation. No Abnormality Detected General Teeth Observations, Clipped Hyperreactive No Ophthalmological Abnormalities Detected Hair Loss, Forepaw, Bilateral Hair Loss, Forepaw, Right Sacrificed by design General observation. No Abnormality Detected Removed from study General observation. No Abnormality Detected Eye Observations, Closed, Left Eye Observations, Partially Closed, Left Eye Observations, Enophthalmus, Left Eye Observations, Eye Observations, Eye Observations, Eye Observations, unable to bleed Eye Observations, Exophchalmus, Left Bled via Orbital for Clin Bled via Orbital for Clin Bled via Orbital for Clin Corneal Opacity, Left Path, Path, Path, Left Right Right, Eye Observations, tail vein Discharge, Nose, Black Discharge, Eye left. Black Discharge, Eye right. Black Sacrificed by design General observation. No Abnormality Detected Eye Observations, Bled via Orbital for Ciin Path, Eye Observations, Bled via Orbital for Clin Path, No Ophthalmological Abnormalities Detected Sacrificed by design Bilateral Right Days 0-35 58-77,84-119,125 112-119,125 80,122 42-77,84-105 125 125 0-74 74 0. 181 84,90,98,105,112,119,126-1 161-175 14-28,35-49,56-70,77-84,90 105,112,119,126-133,140-15 6-7 3,92,125 0,21,34,55,76,89,96,101,10 9 14-28,35-49,56-70,77-84,90 105,112,119,126-133,140-15 160 35 7,56 77-84,90 181 0-42,49-77,84-91 91 44 80 91 636 H-24516: Subchronic Toxicity 90-Day Gavage Study in Rats with One-Generation Reproduction Evaluations Sex Group Animal M III 643173 M III 643290 M III 643272 M III 643292 M III 643228 M III 643308 M III 643264 M III 643240 M III 643180 INDIVIDUAL CLINICAL AND OPHTHALMOLOGICAL OBSERVATIONS AND MORTALITY DA Observation Days General observation. No Abnormality Detected Eye Observations, Bled via Orbital for Clin Path, No Ophthalmological Abnormalities Detected Sacrificed by design Right General observation, No Abnormality Detected Eye Observations, Bled via Orbital for Clin Path, Eye Observations, Bled via Orbital for Clin Path, No Ophthalmological Abnormalities Detected Sacrificed by design Bilateral Right General observation. No Abnormality Detected Eye Observations, Bled via Orbital for Clin Path, Eye Observations, Bled via Orbital for Clin Path, No Ophthalmological Abnormalities Detected Sacrificed by design Bilateral Right 0-42,49-77,84-91 44, 91 80 91 0-42,49-77,84-91 91 44 80 91 0-42,49-77,84-91 91 44 80 91 General observation. No Abnormality Detected Eye Observations, Bled via Orbital for Clin Path, No Ophthalmological Abnormalities Detected Sacrificed by design Right General observation. No Abnormality Detected Eye Observations, Bled via Orbital for Clin Path, "No Ophthalmological Abnormalities Detected Sacrificed by design Right General observation. No Abnormality Detected Eye Observations, Bled via Orbital for Clin Path, No Ophthalmological Abnormalities Detected Hair Loss, Forepaw, Bilateral Sacrificed by design Right 0-42,49-77,84-91 44,91 80 91 0-42,49-77,84-91 44,91 80 91 0-42,49-70 44,91 80 77,84-91 91 General observation. No Abnormality Detected Eye Observations, Bled via Orbital for Clin Path, No Ophthalmological Abnormalities Detected Sacrificed by design Right General observation. No Abnormality Detected Eye Observations, Bled via Orbital for Clin Path, No Ophthalmological Abnormalities Detected Sacrificed by design Right 0-42,49-77,84-91 44,91 80 91 0-42,49-77,84-91 44,91 80 91 General observation. No Abnormality Detected Eye Observations, Bled via Orbital for Clin Path, No Ophthalmological Abnormalities Detected Sacrificed by design Right 0-42,49-77,84-91 44, 91 80 91 637 -24516: Subchronic Toxicity 90-Day Gavage Study in Rats with One-Generation Reproduction Evaluations Sex Group Animal M III 643179 M III 643202 M III 643310 M III 643306 INDIVIDUAL CLINICAL AND OPHTHALMOLOGICAL OBSERVATIONS AND MORTALITY DA Observation General observation. No Abnormality Detected Eye Observations, Bled via Orbital for Clin Path, Mo Ophthalmological Abnormalities Detected Sacrificed by design Right General observation. No Abnormality Detected Eye Observations, Exophthalmus, Left Eye Observations, Bled via Orbital for Clin Path, Eye Observations, Bled via Orbital for Clin Path, Eye Observations, Bled via Orbital for Clin Path, Eye Observations, Corneal Opacity, Left Bilateral Left Right Discharge, Mose, Black Sacrificed by design General observation. No Abnormality Detected Eye Observations, Bled via Orbital for Clin Path, Bilateral Eye Observations, Bled via Orbital for Clin Path, Left Eye Observations, Bled via Orbital for Clin path, Right Discharge, Ear left. Black Discharge, Eye bilateral. Black Discharge, Nose, Black Stain Fur/Skin, Face, Black Sacrificed by design General observation. No Abnormality Detected Eye Observations, Exophthalmus, Left Eye Observations, Bled via Orbital for Eye Observations, Bled via Orbital for Eye Observations, Bled via Orbital for Discharge, Ear left. Black Discharge, Eye left, Black Discharge, Eye right. Black Hair Loss, Forepaw, Left Wound, Superficial, Pace Wound, Superficial, Nose Sacrificed by design Clin Clin Clin Path, Path, Path, Bilateral Left Right Days 0-42,49-77,84-91 44,91 80 91 0,7,14-28,35,70 56,140-154,161 34,55,89,92,115,125 9,21,96,139,160,181 0-3,76,101,108 77-84,90,98,105,112,119,12 140-154,161-181 42-49,56-63 181 0,7,14-28,35-49,56-70,77-8 98,105,147,181 3,55,139 9,21,92-96,115,125,160,181 0,34,76,89,101,108 126 133,140 112,119,126-133,140,154,16 119,126 181 0,7,14,28,35-42,56,70,77-8 112 119,126-133,140-154,161 3,34 9,55,96,115,139,160,181 0,21,76,89,92,101,108,125 126 133,140-147 63 140-154,161-181 21 49 181 638 H-24516: Subchronic Toxicity 90-Day Gavage Study in Rats with One-Generation Reproduction Evaluations Sex Group Animal M III 643305 M III 643293 M III 643287 M III M III M III M III 6431B8 643230 643170 643144 M III M III M III M III 643277 643214 643261 643166 INDIVIDUAL CLINICAL AND OPHTHALMOLOGICAL OBSERVATIONS AND MORTALITY DAT Observation Days General observation. No Abnormality Detected Eye Observations, Bled via Orbital for Eye Observations, Bled via Orbital for Eye Observations, Bled via Orbital for General Teeth Observations, Clipped Breathing Observations, Noise Discharge, Eye left. Black Sacrificed by design Clin Clin Clin Path, Path, Path, Bilateral Left Right 0,7,14-28,35-49,56-70,77-8 98,105,112 160,181 9,21,55,96,101,108,115,125 0-3,34,76,89,92 119,126-133,140-154,161-17 147-154,161-181 126 181 General observation. No Abnormality Detected Eye Observations, Bled via Orbital for Clin Path, Left Eye Observations, Bled via Orbital for Clin Path, Right Discharge, Eye right. Black Hair Loss, Forelimb, Bilateral Hair Loss, Forepaw, Bilateral Hair Loss, Forepaw, Right Sacrificed by design 0,7,14-28,35-49,56-70,77-8 98,105,112,119,133,140-154 9,21,55,96,108,139,160,181 0-3,34,76,89,92,101,115,12 126 181 181 175 181 General observation. No Abnormality Detected Hair Loss, Forepaw, Bilateral Removed from study 0-14,56-74 21-49 74 General observation. No Abnormality Detected Removed from study 0-74 74 General observation. No Abnormality Detected Removed from study 0-74 74 General observation, No Abnormality Detected Removed from study 0-74 74 General observation, No Abnormality Detected Hair Loss, Forepaw, Right Removed from study 0-21 28-74 74 General observation. No Abnormality Detected Removed from study 0-74 74 General observation. No Abnormality Detected Removed from study 0-74 74 General observation. No Abnormality Detected Removed from study 0-74 74 General observation. No Abnormality Detected Removed from study 0-74 74 639 [-24516: Subchronic Toxicity 90-Day Gavage Study in Rats with One-Generation Reproduction Evaluations INDIVIDUAL CLINICAL AND OPHTHALMOLOGICAL OBSERVATIONS AND MORTALITY DA Sex Group Animal Observation Days M III 643153 General observation, No Abnormality Detected Removed from study 0-74 74 M III 643177 General observation. No Abnormality Detected Removed from study 0-74 74 M III 643198 General observation. No Abnormality Hair Loss, Forepaw, Bilateral Hair Loss, Forepaw, Left Wound, Superficial, Tail Removed from study Detected 0-14 21-49 56-74 21-74 74 M III 643291 General observation. No Abnormality Detected Removed from study 6-74 74 M III 643184 General observation, No Abnormality Detected Removed from study 0-74 74 M III 643167 General observation. No Abnormality Detected Removed from study 0-74 74 M III 643223 General observation, No Abnormality Detected Removed from study 0-74 74 M III 643233 .General observation. No Abnormality Detected General Teeth Observations, Absent General Teeth Observations, Clipped Removed from study 0-49,74 56-63 58-70 74 M III 643183 General observation. No Abnormality Detected Removed from study 0-74 74 M III 643219 General observation. No Abnormality Detected Removed from study 0-74 74 M III 643263 General observation. No Abnormality Detected Removed from study 0-74 74 640 H-24516: Subchronic Toxicity 90-Day Gavage Study in Rats with One-Generation Reproduction Evaluations Sex Group Animal M V 643250 M V 643243 M V 643311 M V 643318 M V 643247 M V 643175 INDIVIDUAL CLINICAL AND OPHTHALMOLOGICAL OBSERVATIONS AND MORTALITY DA Observation Days General observation. No Abnormality Detected Eye Observations, Bled via Orbital for Clin Path, No Ophthalmological Abnormalities Detected Sacrificed by design Right 0-42,49-77,84-91 44,91 80 91 General observation. No Abnormality Detected Eye Observations, Bled via Orbital for Clin Path, Eye Observations, Bled via Orbital for Clin Path, No Ophthalmological Abnormalities Detected Sacrificed by design Left Right 0-42,49-77,84-91 44 91 80 91 General observation. No Abnormality Detected Eye Observations, Bled via Orbital for Clin Path, No Ophthalmological Abnormalities Detected Sacrificed by design Right 0-42,49-77,84-91 44,91 80 91 General observation, No Abnormality Detected Eye Observations, Bled via Orbital for Clin Path, Mo Ophthalmological Abnormalities Detected Sacrificed by design Right 0-42,49-77,84-91 44,91 80 91 General observation. No Abnormality Detected Eye Observations, Bled via Orbital for Clin Path, Right Mo Ophthalmological Abnormalities Detected Hair Loss, Thoracic, Ventral Mass Thoracic, Lateral, Mass ftl, Ulcerated, 1.5 cm Mass Thoracic, Lateral, Mass #1, Not Ulcerated, 2.0 CM Mass Thoracic, Lateral, Mass fl. Not Ulcerated, 1.5 CM Sacrificed by design 0-42,49-56 44,91 80 91 84-90 77 58-70 91 General observation. No Abnormality Detected Eye Observations, Bled via Orbital for Clin Path, Breathing Observations, Past Breathing Observations, Labored Discharge, Mouth, Red Discharge, Mose, Black Muscle Tone, Decreased Pale Comments, excessive toe nail bleed Comments, 2ml blood Stain Pur/Skin, Inguen, Brown Stain Fur/Skin, Perineum, Brown Stained Cageboard, Red, alot of red from toe nail Accidentally Killed Right 0-42,49-56 44 77 77 66-76 63-76 73-77 73-77 76 66 77 73-77 73-77 77 641 H-24516: Subchronic Toxicity 90-Day Gavage Study in Rats with One-Generation Reproduction Evaluations Sex Group Animal M V 643314 M V 643275 M V 643257 M V 643224 M V 643169 INDIVIDUAL CLINICAL AND OPHTHALMOLOGICAL OBSERVATIONS AND MORTALITY DAT Observation Days General observation. No Abnormality Detected Eye Observations, Bled via Orbital for Clin Path, General Teeth Observations, Absent No Ophthalmological Abnormalities Detected Sacrificed by design Right 0-42,49-77 44,91 84-91 80 91 General observation, No Abnormality Detected Eye Observations, Bled via Orbital for Clin Path, Eye Observations, Bled via Orbital for Clin Path, No Ophthalmological Abnormalities Detected Sacrificed by design Left Right 0-42,49-77,84-91 44 91 80 91 General observation. No Abnormality Detected Eye Observations, Bled via Orbital for Clin Path, Eye Observations, Bled via Orbital for Clin Path, No Ophthalmological Abnormalities Detected Sacrificed by design Bilateral Right 0-42,49-77,84-91 91 44 80 91 General observation, No Abnormality Detected Eye Observations, Bled via Orbital for Clin Path, No Ophthalmological Abnormalities Detected Sacrificed by design Right 0-42,49-77,84-91 44,91 80 91 General observation, No Abnormality Detected 'Eye Observations, Partially Closed, Left Eye Observations, Partially Closed Eye Observations, Enophthalmus, Left Eye Observations, Eye Observations, Eye Observations, Eye Observations, Eye Observations, by tail vein Eye Observations, Exophthalmus, Le t Bled via Orbital for Bled via Orbital for Bled via Orbital for Bled via Orbital for Clin Clin Clin Clin Path, Path, Path, Path, Corneal Opacity, Left Bilateral Left Right Right, bled Discharge, Eye left. Black Hair Loss, Face, Left Swollen Observations, Face Sacrificed by design 0,7,14-28,35-49 133,140-154,161-181 119,126 77-84,90,98,105,112,119,12 140-154,161-175 56-70 55 9,21,115 0-3,34,76,89,92-96,101,125 108 77-84,90,98,105,112,119,12 140-154,161-175 56-63 70,77-84,90,98,105 56-70,77-84 181 642 1. H-24516: Subchronic Toxicity 90-Day Gavage Study in Rats with One-Generation Reproduction Evaluations Sex Group Animal M V 643159 M V 643286 M V 643181 M V 643206 M V M V 643313 643182 INDIVIDUAL CLINICAL AND OPHTHALMOLOGICAL OBSERVATIONS AND MORTALITY DAT Observation Days General observation, No Abnormality Detected Eye Observations Exophthalmus, Left Eye Observations Bled via Orbital for Clin Path, Eye Observations Bled via Orbital for Clin Path, Eye Observations Corneal Opacity, Bilateral Eye Observations Corneal Opacity, Right Left Right General Teeth Observations, Maloccluded General Teeth Observations, Clipped Hyperreactive Discharge, Eye left, Black Discharge, Eye right. Black Sacrificed by design 0 161-181 9,21,55,96,108,139,160,181 0-3,34,76,89,92,101,115,12 175-181 7,14-28,35-49,56-70,77-84, 98,105,112,119,126-133,140 119,126-133,140-154,161-18 77-84,90,98,105,112,119,12 140-154,161-175 126-133,140-154,161-175 126-133,140-154,161-168,18 35 181 General observation, No Abnormality Detected Eye Observations, Partially Closed, Left Eye Observations, Bled via Orbital for Clin Eye Observations, Bled via Orbital for Clin Discharge, Eye left. Black Sacrificed by design Path, Path, Left Right General observation, No Abnormality Detected Eye Observations, Bled via Orbital for Clin Path, Bilateral Eye Observations, Bled via Orbital for Clin Path, Left Eye Observations, Bled via Orbital Eye Observations, Corneal Opacity, Comments, compound evident on lips Sacrificed by design for Clin Right Path, Right 0,7,14-28,35-49,56-70,77-8 98,105,112,119,133,140-154 126 3,21,55,96,108,115,125,139 0,9,34,76,89,92,101 126 181 0,7,14-28,35-49,56-70,77,8 90 0 9,21,55,76,89,92-96,101,10 181 3,34,125 98,105,112,119,126-133,140 81 181 General observation. No Abnormality Detected Eye Observations, Exophthalmus, Right Eye Observations, Bled via Orbital for Eye Observations, Bled via Orbital for Eye Observations, Bled via Orbital for Discharge, Eye right. Black Sacrificed by design Clin Clin Clin Path, Path, Path, Bilateral Left Right General observation. No Abnormality Detected Removed from study 0,7,14-28,42-49,56-70,77-8 98,105,112,119,126-133,140 35 76,108,115,125,139 3,9,21,55,96,160,181 0,34,89,92,101 35 181 0-74 74 General observation. No Abnormality Detected Removed from study 0-74 74 643 H-24516: Subchronic Toxicity 90-Day Gavage Study in Rats with One-Generation Reproduction Evaluations INDIVIDUAL CLIKiICfLL AND OPH'1'HALMOLOGICAL 0 BSERVATIONS AND MORTALITY DAT Sex Group Animal Observation Days M V 643146 General observation, No Abnormality Detected Hair Loss, Forepaw, Right Removed from study 0-70 74 74 M V 643312 General observation, Mo Abnormality Detected Removed from study 0-74 74 M V 643199 General observation, No Abnormality Detected Removed from study 0-74 74 M V 643267 General observation, No Abnormality Detected Removed from study 0-74 74 M V 643216 General observation, No Abnormality Detected Removed from study 0-74 74 M V 643244 General observation, No Abnormality Detected Hyperreact ive Removed from study 0-14,63-74 21-56 74 M V 643245 General observation, No Abnormality Detected Removed from study 0-74 74 M V 643301 General observation, No Abnormality Detected Hair Loss, Forelimb, Left Removed from study 0-70 : 74 74 a) :M V 643200 General observation, No Abnormality Detected .1 Removed from study w M V 643255 GReemnoevreadl ofrbosmersvtautdioyn, No Abnormality Detected a N" (D M V 643157 General observation, No Abnormality Detected a Hyperreactive 0 Removed from study 0 (D CA M V 643238 General observation, No Abnormality Detected 3 Removed from study ^ .1 M V 643227 General observation, No Abnormality Detected J Removed from study 7 j" M V 643164 General observation, NO Abnormality Detected ^ Removed from study 1 5 0-74 74 0-74 74 0-49 56-74 74 0-74 74 ; 0-74 74 0-74 74 644 1-24516: Subchronic Toxicity 90-Day Gavage Study in Rats with One-Generation Reproduction Evaluations Sex Group Animal M V 643154 M V 643156 M V 643208 M V 643190 INDIVIDUAL CLINICAL AND OPHTHALMOLOGICAL OBSERVATIONS AND MORTALITY DA Observation Days General observation. No Abnormality Detected Removed from study 0-74 74 General observation. No Abnormality Detected Removed from study 0-74 74 General observation, No Abnormality Detected Removed from study 0-74 74 General observation, No Abnormality Detected Removed from study 0-74 74 645 H-24516: Subchronic Toxicity 90-Day Gavage Study in Rats with One-Generation Reproduction Evaluations Sex Group Animal M VII 643194 M VII. 643252 M VII 643260 M, VII 643315 M VII 643215 M, VII 643193 M VII 643298 INDIVIDUAL CLINICAL AND OPHTHALMOLOGICAL OBSERVATIONS AND MORTALITY DA Observation Days General observation. No Abnormality Detected Eye Observations, Bled via Orbital for Clin Path, No Ophthalmological Abnormalities Detected Sacrificed by design Right General observation. No Abnormality Detected Eye Observations, Bled via Orbital for Clin Path, General Teeth Observations, Clipped No Ophthalmological Abnormalities Detected Sacrificed by design Right 0-42,49-77,84-91 44,91 80 91 0-42,49-70 44,91 77,84-91 80 91 General observation. No Abnormality Detected Eye Observations, Bled via Orbital for Clin Path, No Ophthalmological Abnormalities Detected Wound, Superficial, Shoulder, Left Sacrificed by design Right 0,42,49-77,84-91 44,91 80 7-35 91 Eye Observations, Bled via Orbital for Clin General Teeth Observations, Clipped No Ophthalmological Abnormalities Detected Hair Loss, Forepaw, Bilateral Hair Loss, Forepaw, Left Sacrificed by design Path, Right 44,91 84-91 80 42,49-77,84-91 0-35 91 'General observation, NO Abnormality Detected Eye Observations, Bled via Orbital for Clin Path, General Teeth Observations, Clipped Mo Ophthalmological Abnormalities Detected Stain Fur/Skin, Forepaw. Left, Red Stain Fur/Skin, Perineum, Red Stain Pur/Skin, Face, Red Sacrificed by design Right General observation. No Abnormality Detected Eye Observations, Bled via Orbital for Clin Path, General Teeth Observations, Clipped No Ophthalmological Abnormalities Detected Comments, compound present on mouth Sacrificed by design Right 0-42,49-63 44, 91 77,84-91 80 70 70 70 91 0-42,49-56 44,91 57-77,84-91 80 57 91 General observation. No Abnormality Detected Eye Observations, Bled via Orbital for Ciin Path, General Teeth Observations, Clipped No Ophthalmological Abnormalities Detected Swollen Observations, Nose Sacrificed by design Right 0-42,49-77 44,91 84-91 80 84 91 646 T-24516: Subchronic Toxicity 90-Day Gavage Study in Rats with One-Generation Reproduction Evaluations Sex Group Animal M VII 643201 M VII 643259 M VII 643174 M VII 643283 M VII 643149 INDIVIDUAL CLINICAL AND OPHTHALMOLOGICAL OBSERVATIONS AND MORTALITY DAT Observation Days General observation. No Abnormality Detected Eye Observations, Bled via Orbital for Clin Path, General Teeth Observations, Clipped No Ophthalmological Abnormalities Detected Misshapen Observations, Tail Sacrificed by design Right 0 44,91 84-91 80 7-42,49-77,84-91 91 General observation. No Abnormality Detected 0-42,49-56 Eye Observations, Bled via Orbital for Clin Path, Bilateral 91 Eye Observations, Bled via Orbital for Clin Path, Right 44 General Teeth Observations, Clipped 57-77,84-91 : Mo Ophthalmological Abnormalities Detected 80 Sacrificed by design 91 General observation. No Abnormality Detected Eye Observations, Bled via Orbital for Clin Path, Eye Observations, Bled via Orbital for Clin Path, Mo Ophthalmological Abnormalities Detected Sacrificed by design Bilateral Right 0-42,49-77,84-91 44 91 80 91 General observation. No Abnormality Detected Eye Observations, Bled via Orbital for Clin Path, Eye Observations, Bled via Orbital for Clin Path, Eye Observations, Bled via Orbital for Clin Path, General Teeth Observations, Broken "General Teeth Observations, Maloccluded Bilateral Left Right General Teeth Observations, Clipped Discharge, Nose, Black Sacrificed by design 0,7,14-28,35-49,56 76,160 9,21,55,96,108,139,181 0-3,34,89,92,101,115,125 70 58-70,77-84,90,98,105,112, 140-154,161-181 58-70,77-84,90,98,105,112, 140-154,161-175 112,119 181 General observation. No Abnormality Detected Eye Observations, Bled via Orbital for Clin Path, Eye Observations, Bled via Orbital for Clin Path, Eye Observations, Bled via Orbital for Clin Path, General Teeth Observations, Clipped Hyperreactive Discharge, Nose, Black Hair Loss, Forepaw, Bilateral Bilateral Left Right ' Sacrificed by design 0,7,14,181 101 3,21,55,96,108,115,125,139 0,9,34,76,89,92 119,126-133,140-154,161-17 133,140-154,161-175 112,119,126 21-28,35-49,56-70,77-84,90 105 181 647 H-24516: Subchronic Toxicity 90-Day Gavage Study in Rats with One-Generation Reproduction Evaluations Sex Group Animal M VII 643178 M VII 643152 M VII 643295 M VII 643289 M VII 643171 INDIVIDUAL CLINICAL AND OPHTHALMOLOGICAL OBSERVATIONS AND MORTALITY DAT Observation Days General observation. No Abnormality Detected Eye Observations, Partially Closed, Ri9ht Eye Observations, Enophthalmus, Right Eye Observations, Exophthalmus, Right Eye Observations, Bled via Orbital for Clin Path, Left Eye Observations, Bled via Orbital for Clin Path, Right Eye Observations, Bled via Orbital for Clin Path, unable to bleed Eye Observations, Cornea! Opacity, Right General Teeth Observations, Clipped Discharge, Nose, Brown Wound, Superficial, Mouth Sacrificed by design 0,7,14-21 119,126-133,140-154,161-18 77-84,90,98,105,112,119,12 140-154,161-181 28,35-54,56-70 9,55,76,89,92-96,108,115,12 0-3,34,101 21 28,35-54,56- 70,77-84,90,98 119,126-133, 140-154,161-18 54,56-70,77- 84,90,98,105,1 126-133,140- 154,161-175 28 28,35 181 General observation. No Abnormality Detected Eye Observations, Bled via Orbital for Eye Observations, Bled via Orbital for Eye Observations, Bled via Orbital for General Teeth Observations, Clipped Discharge, Eye right. Black Comments, compound evident on mouth Sacrificed by design Clin Clin Clin Path, Path, Path, Bilateral Left Right 0,7,14-28,35-49,63-70,77-8 98,105,181 55,76,89,92 9,21,96,101,108,115,125,13 0-3,34 112,119,126-133,140-154,16 56 10 181 General observation. No Abnormality Detected Eye Observations, Bled via Orbital for Clin Path, Eye Observations, Bled via Orbital for Clin Path, General Teeth Observations, Clipped Left Right Sacrificed by design 0,7,14-28,35-49,56,181 9,21,55,96,108,139,160,181 0-3,34,76,89,92,101,115,12 57-70,77-84,90,98,105,112,1 140-154,161-175 181 General observation. No Abnormality Detected General Teeth Observations, Clipped Removed from study 0-49,74 54-70 74 General observation. No Abnormality Detected General Teeth Observations, Broken General Teeth Observations, Clipped Discharge, Nose, Red Discharge, Eye right. Red Hair Loss, Forepaw, Bilateral Hair Loss, Porepaw, Left Stain Fur/Skin, Perineum, Red Stain Fur/Skin, Periocular, Right, Brown Removed from study 0 70-74 70 70 70 14-74 7 70 74 74 648 H-24516: Subchronic Toxicity 90-Day Gavage Study in Rats with One-Generation Reproduction Evaluations Sex Group Animal M VII 643158 M VII 643249 M VII 643161 M VII 643309 M VII 643248 M VII 643285 M VII 643278 M VII M VII 643299 643274 INDIVIDUAL CLINICAL AND OPHTHALMOLOGICAL OBSERVATIONS AND MORTALITY D Observation Days General observation, No Abnormality Detected Removed from study 0-74 74 General observation, No Abnormality General Teeth Observations, Broken General Teeth Observations, Clipped Discharge, Nose, Black Diarrhea, Brown Stain Fur/Skin, Forepaw, Bilateral, Removed from study Detected Red 0-63 70-74 70 70 70 70 74 General observation. No Abnormality Detected General Teeth Observations, Clipped Removed from study 0-63,74 '70 74 General observation. No Abnormality General Teeth Observations, Clipped Breathing Observations, Breathing Observations, Discharge, Mouth, Red Discharge, Nose, Red Labored Noise Stain Fur/Skin, Forepaw, Bilateral, Stain Fur/Skin, Perineum, Yellow Accidentally Killed Detected Red 0-49 54-70 70 69 69-70 70 70 70 70 General observation. No Abnormality Detected General Teeth Observations, Absent General Teeth Observations, Clipped Removed from study 0-63,74 70 70 74 General observation. No Abnormality Detected Abnormal Gait, Hindlimb, Left Swollen Observations, Hindlimb, Left Removed from study 0-56,74 63-70 63-70 74 General observation. No Abnormality Detected Discharge, Mouth, Clear Removed from study 0-28,56-74 31-49 74 General observation. No Abnormality Detected Removed from study 0-74 74 General observation. No Abnormality Detected Hyperreactive Removed from study 0-14,56-74 21-49 74 649 H-24516: SubchronicToxicity 90-Day Gavage Study in Rats with One-Generation Reproduction Evaluations Sex Group Animal M VII 643192 M VII M VII 643222 643160 M VII M VII 643191 643203 M VII 643282 M VII 643302 M VII M VII 643317 643225 INDIVIDUAL CLINICAL AND OPHTHALMOLOGICAL OBSERVATIONS AND MORTALITY DA Observation Days General observation. No Abnormality Comments, teeth loose General Teeth Observations, Broken General Teeth Observations, Clipped Comments, teeth loose Removed from study Detected 0-63 67 70-74 70 67 74 General observation, No Abnormality Detected Removed from study 0-74 74 General observation. No Abnormality Detected General Teeth Observations, Broken General Teeth Observations, Clipped Removed from study 0-63 .74 70 74 General observation. No Abnormality Detected Removed from study 0-74 74 General observation. No Abnormality General Teeth Observations, Absent General Teeth Observations, Clipped Discharge, Mouth, Clear Removed from study Detected 0-28,56-70 74 74 34-49 74 General observation, No Abnormality Detected General Teeth Observations, Absent General Teeth Observations, Clipped Removed from study 0-63 70-74 70 74 General observation. No Abnormality Detected General Teeth Observations, Clipped Discharge, Eye right, Red Stain Fur/Skin, Periocular, Bilateral, Black Removed from study 0-63 74 70 74 74 General observation. No Abnormality Detected Removed from study 0-74 74 General observation. No Abnormality Detected General Teeth Observations, Clipped No Ophthalmological Abnormalities Detected Sacrificed by design 0-49 54-77,84-119,125 80,122 125 650 H-24516: Subchronic Toxicity 90-Day Gavage Study in Rats with One-Generation Reproduction Evaluations Sex Group Animal M VII 643296 M VII 643258 M VII 643316 M VII 643220 M VII 643236 M VII 643165 M VII 643266 INDIVIDUAL CLINICAL AND OPHTHALMOLOGICAL OBSERVATIONS AND MORTALITY DA Observation Days General observation. No Abnormality Detected General Teeth Observations, Broken General Teeth Observations, Clipped No Ophthalmological Abnormalities Detected Diarrhea, Brown Stain Fur/Skin, Tail, Stain Fur/Skin, Chin, Sacrificed by design Brown Red 0-63 70-77,84-90 98-119,125 80,122 70 119,125 70 125 General observation. No Abnormality Detected No Ophthalmological Abnormalities Detected Comments, animal did not receive whole dose Stain Fur/Skin, Perineum, Red Sacrificed by design General observation. No Abnormality Detected General Teeth Observations, Clipped No Ophthalmological Abnormalities Detected Sacrificed by design 0-35,42-63,84-119,125 80,122 41 70-77 125 0-77,84-105 112-119,125 80,122 125 General observation, No Abnormality Detected Eye Observations, Enophthalmus, Right General Teeth Observations, Absent General Teeth Observations, Broken General Teeth Observations, Clipped No Ophthalmological Abnormalities Detected Sacrificed by design General observation. No Abnormality Detected General Teeth Observations, Absent General Teeth Observations, Broken General Teeth Observations, Clipped Discharge, Mouth, Clear No Ophthalmological Abnormalities Detected Sacrificed by design General observation. No Abnormality Detected General Teeth Observations, Broken General Teeth Observations, Clipped No Ophthalmological Abnormalities Detected Sacrificed by design General observation, No Abnormality Detected General Teeth Observations, Clipped No Ophthalmological Abnormalities Detected Sacrificed by design 0-28 35-77,84-119,125 63 70-77,84-119,125 63-77,84-119,125 80,122 125 0-21,35-56 63-70 70 63-77,84-119,125 28-34 80,122 125 0-70 76-77,84-90 87-119,125 80,122 125 0-70 77,84-119,125 80,122 125 651 H-24516: Subchronic Toxicity 90-Day Gavage Study in Rats with One-Generation Reproduction Evaluations INDIVIDUAL CLINICAL AND OPHTHALMOLOGICAL OBSERVATIONS AND MORTALITY DAT Sex Group Animal M VII 643151 M VII 643234 M VII 643281 Observation General observation. No Abnormality Detected General Teeth Observations, Clipped Mo Ophthaltnological Abnormalities Detected Hair Loss, Forelimb, Left Sacrificed by design . General observation. No Abnormality Detected General Teeth Observations, Broken General Teeth Observations, Clipped Aggressive Behavior Hyperreactive Mo Ophthalmological Abnormalities Detected Hair Loss, Forepaw, Bilateral Sacrificed by design General observation. No Abnormality Detected Removed from study, rat physically removed 2/24/01 Days 0-77,84-90 98-119,125 80,122 125 125 0 80-90 70-119,125 119,125 90-119,125 80,122 7-119,125 125 0-74 80 652 H-24516: Subchronic Toxicity 90-Day Gavage Study in Rats with One-Generation Reproduction Evaluations Sex Group Animal F II 643477 F II 643374 F II 643406 F II 643486 F II 643361 F II 643463 P II 643398 F II 643436 F II 643362 INDIVIDUAL CLINICAL AND OPHTHALMOLOGICAL OBSERVATIONS AND MORTALITY DA Observation Days General observation, No Abnormality Detected Eye Observations, Bled via Orbital for Clin Path, Eye Observations, Bled via Orbital for Clin Path, Ho Ophthalmological Abnormalities Detected Sacrificed by design Bilateral Right 0-42,49-77,84-91,93 45,92 93 80 93 General observation. No Abnormality Detected Eye Observations, Bled via Orbital for Clin Path, No Ophthalmological Abnormalities Detected Sacrificed by design Right 0-42,49-77,84-91,93 45,92-93 80 93 General observation, No Abnormality Detected Eye Observations, Bled via Orbital for Clin Path, No Ophthalmological Abnormalities Detected Sacrificed by design Right 0-42,49-77,84-93 45,93 80 93 General observation. No Abnormality Detected Eye Observations, Bled via Orbital for Clin Path, No Ophthalmological Abnormalities Detected Sacrificed by design Right General observation. No Abnormality Detected Eye Observations, Bled via Orbital for Clin Path, No Ophthalmological Abnormalities Detected Sacrificed by design Right 0-42,49-77,84-93 45,93 80 93 0-42,49-77,84-93 45,93 80 93 General observation. No Abnormality Detected Eye Observations, Bled via Orbital for Clin Path, No Ophthalmological Abnormalities Detected Sacrificed by design Right 0-42,49-77,84-93 45,93 80 93 General observation. No Abnormality Detected Eye Observations, Bled via Orbital for Clin Path, No Ophthalmological Abnormalities Detected Sacrificed by design Right 0-42,49-77,84-93 45,93 80 93 General observation, No Abnormality Detected Eye Observations, Bled via Orbital for Clin Path, No Ophthalmological Abnormalities Detected Sacrificed by design Right General observation. No Abnormality Detected Eye Observations, Bled via Orbital for Clin Path, No Ophthalmological Abnormalities Detected Sacrificed by design Right 0-42,49-77,84-93 45,93 80 93 0-42,49-77,84-93 45,93 80 93 653 H-24516: Subchronic Toxicity 90-Day Gavage Study in Rats with One-Generation Reproduction Evaluations Sex Group Animal F II 643354 F II 643402 F II 643383 F II 643465 INDIVIDUAL CLINICAL AND OPHTHALMOLOGICAL OBSERVATIONS AND MORTALITY DA Observation Days General observation. No Abnormality Detected Eye Observations, Bled via Orbital for Clin Path, No Ophthalmological Abnormalities Detected Sacrificed by design Right 0-42,49-77,84-93 45,93 80 93 General observation. No Abnormality Detected Eye Observations, Closed, Left Eye Observations, Partially Closed, Left Eye Observations, Enophthalmus, Left Eye Observations, Exophthalmus, Left Eye Observations, Bled via Orbital for Clin Path, Left Eye Observations, Bled via Orbital for Clin Path, Right Eye Observations, Corneal Opacity, Left Discharge, Nose, Black Hair Loss, Face, Left Sacrificed by design General observation. No Abnormality Detected Eye Observations, Bled via Orbital for Clin Path, Bilateral Eye Observations, Bled via Orbital for Clin Path, Left Eye Observations, Bled via Orbital for Clin Path, Right Breathing Observations, Noise Discharge Eye bilateral. Black Discharge Eye bilateral. Brown Discharge. .Nose, Black Discharge Eye right, Black Discharge Eye right, Brown Sacrificed by design General observation. No Abnormality Detected Eye Observations, Bled via Orbital for Clin Path, Bilateral Eye Observations, Bled via Orbital for Clin Path, Left Eye Observations, Bled via Orbital for Clin Path, Right Discharge, Eye bilateral, Black Discharge, Eye right. Black Hair Loss, Face, Right Sacrificed by design 0,7,14-28,35-49 175-181 112,119,126-133,140-154,16 77-84,91,98,105,112,119,12 140-154,161-181 56-70 9,21 0-3,34,55,76,89,92-96,101 139,160,181 70,77-84,91,98,105,112,11 140-154,161-181 105 70 181 0,7,14-28,35-49,56-70,77-8 147-154 55 9,21,96,108,160,181 0-3,34,76,89,92,101,115,12 140 98,105,112.119,126-133 161 98,105,112 140 168-181 181 0,7,14-28,35-49,56-70,77-8 98,119,147-154,161-181 0 9,21,96,139,160,181 3, 34, 55, 76, 89, 92 ,101,108,1 133,140 105,126 112 181 654 I H-24516: Subchronic Toxicity 90-Day Gavage Study in Rats with One-Generation Reproduction Evaluations Sex Group Animal P II 643484 F II 643384 P II F II F II F II F II F II F II F II F II 643352 643343 643459 643394 643480 643319 643350 643363 643397 INDIVIDUAL CLINICAL AND OPHTHALMOLOGICAL OBSERVATIONS AND MORTALITY DA Observation Days General observation. No Abnormality Detected Eye Observations Exophthalmus, Right Eye Observations Bled via Orbital for Clin Path, Eye Observations Bled via Orbital for Clin Path, Eye Observations Bled via Orbital for Clin Path, Eye Observations Corneal Opacity, Bilateral Bilateral Left Right Eye Observations, Corneal Opacity, Breathing Observations, Noise Discharge, Eye bilateral. Black Discharge, Eye right. Black Sacrificed by design Left 0,7,14-21 35-49 3,9,21,34,55,76,160 96,139,181 0,89,92,101,108,115,125 35-49,56-70,77-84,91,98,1 119,126-133,140-154,161-1 28 140-154,161-181 77 35-42,56 181 General observation, No Abnormality Detected Eye Observations, Exophthalmus, Left Eye Observations, Bled via Orbital for Eye Observations, Bled via Orbital for Sacrificed by design Clin Clin Path, Path, Left Right 0,7,14-28,35-49,56-70,7798,105,112,147-154,161-18 119,126-133,140 9,21,96,108,115,125,139,1 0-3,34,55,76,89,92,101,16 181 General observation, No Abnormality Detected Removed from study 0-74 74 General observation, No Abnormality Detected Removed from study 0-74 74 General observation. No Abnormality Detected Removed from study 0-74 74 General observation, No Abnormality Detected Removed from study 0-74 74 General observation. No Abnormality Detected Removed from study 0-74 74 General observation. No Abnormality Detected Removed from study 0-74 74 General observation, No Abnormality Detected Removed from study 0-74 74 General observation, No Abnormality Detected Removed from study 0-74 74 General observation, Mo Abnormality Detected Removed from study 0-74 74 655 H-24516: Subchronic Toxicity 90-Day Gavage Study in Rats with One-Generation Reproduction Evaluations Sex Group Animal F II 643421 F II 643420 F II 643419 F II 643414 P II 643401 F II 643455 F II 643378 F II 643393 F II 643447 F II 643478 F II 643386 F II 643405 F II F II 643425 643448 INDIVIDUAL CLINICAL AND OPHTHALMOLOGICAL OBSERVATIONS AND MORTALITY DA Observation Days General observation. No Abnormality Detected Removed from study 0-74 74 General observation. No Abnormality Detected Removed from study 0-74 74 General observation, No Abnormality Detected Removed from study 0-74 74 General observation. No Abnormality Detected Removed from study 0-74 74 General observation. No Abnormality Detected Removed from study 0-74 74 General observation, No Abnormality Detected Removed from study 0-74 74 General observation. No Abnormality Detected Removed from study 0-74 74 General observation. No Abnormality Detected Removed from study 0-74 74 General observation. No Abnormality Detected Removed from study 0-74 74 General observation. No Abnormality Detected Removed from study 0-74 74 General observation. No Abnormality Detected Removed from study 0-74 74 General observation. No Abnormality Detected No Ophthalmological Abnormalities Detected Hair Loss, Forelimb, Bilateral Hair Loss, Forelimb, Left Sacrificed by design General observation. No Abnormality Detected No Ophthalmological Abnormalities Detected Sacrificed by design 0-21 80,122 28-77,84-112 119,125 125 0-77,84-119,125 80,122 125 General observation, No Abnormality Detected Mo Ophthalmological Abnormalities Detected Hair Loss, Forepaw, Bilateral Sacrificed by design 0-56,112-119,125 80,122 63-77,84-105 125 656 H-24516: Subchronic Toxicity 90-Day Gavage Study in Rats with One-Generation Reproduction Evaluations Sex Group Animal F II 643426 F II 643415 F II 643453 F II 643330 F II 643336 F II F II 643387 643377 INDIVIDUAL CLINICAL AND OPHTHALMOLOGICAL OBSERVATIONS AND MORTALITY DA Observation Days General observation. No Abnormality Detected No Ophthalmological Abnormalities Detected Sacrificed by design General observation. No Abnormality Detected No Ophthalmological Abnormalities Detected Sacrificed by design 0-77,84-119,125 80,122 125 0-77,84-119,125 80,122 125 General observation. No Abnormality Detected No Ophthalmological Abnormalities Detected Sacrificed by design 0-77,84-119,125 80,122 125 General observation. No Abnormality Detected No Ophthalmological Abnormalities Detected Sacrificed by design 0-77,84-119,125 80,122 125 General observation. No Abnormality Detected Discharge, Vulva, Red No Ophthalmological Abnormalities Detected Mass Perineum, Mass ftl. Ulcerated, 1.0 cm Sacrificed in extremis General observation. No Abnormality Detected No Ophthalmological Abnormalities Detected Sacrificed by design General observation. No Abnormality Detected No Ophthalmological Abnormalities Detected Sacrificed .by design 0-77,84-98 105 80 105 105 0-77,84-119,125 80,122 125 0-77,84-119,125 80,122 125 657 H-24516: Subchronic Toxicity 90-Day Gavage Study in Rats with One-Generation Reproduction Evaluations Sex Group Animal F IV 643390 F IV 643396 P IV 643380 F IV 643433 F IV 643389 F IV 643410 F IV 643321 F IV 643324 INDIVIDUAL CLINICAL AND OPHTHALMOLOGICAL OBSERVATIONS AND MORTALITY DA Observation Days General observation, No Abnormality Detected Eye Observations, Bled via Orbital for Clin Path, No Ophthalmological Abnormalities Detected Sacrificed by design Right 0-42,49-77,84-91,93 45,92-93 80 93 General observation. No Abnormality Detected Eye Observations, Bled via Orbital for Clin Path, No Ophthalmological Abnormalities Detected Hair Loss, Side, Left Sacrificed by design Right 0-42,49-77 45,92-93 80 84-91,93 93 General observation. No Abnormality Detected Eye Observations, Bled via Orbital or Clin Path, No Ophthalmological Abnormalities Detected Sacrificed by design Right 0-42,49-77,84-93 45, 93 80 93 General observation. No Abnormality Detected Eye Observations, Bled via Orbital for Clin Path, No Ophthalmological Abnormalities Detected Sacrificed by design Right 0-42,49-77,84-93 45, 93 80 93 General observation, No Abnormality Detected Eye Observations, Bled via Orbital for Clin Path, General Teeth Observations, Clipped Discharge, Eye right. Black No Ophthalmological Abnormalities Detected Sacrificed by design Right 0-42,49-56 45,93 58-77,84-93 63-70 80 93 General observation, No Abnormality Detected Eye Observations, Bled via Orbital for Clin Path, No Ophthalmological Abnormalities Detected Sacrificed by design Right 0-42,49-77,84-93 45,93 80 93 General observation, No Abnormality Abnormal Vocalization Convulsions, Clonic, went stiff Breathing Observations, Fast Prostrate Diarrhea, Brown Sacrificed in extremis Detected 0-28 29 29 29 29 29 29 General observation, No Abnormality Detected Eye Observations, Bled via Orbital for Clin Path, Hyperactive No Ophthalmological Abnormalities Detected Sacrificed by design Right 0-42,49 45,93 56-77,84-93 80 93 658 n H-24516: Subchronic Toxicity 90-Day Gavage Study in Rats with One-Generation Reproduction Evaluations INDIVIDUAL CLINICAL AND OPHTHALMOLOGICAL OBSERVATIONS AND MORTALITY DA Sex Group Animal Observation Days F IV F IV F IV 643458 643364 643483 General observation. No Abnormality Detected Eye Observations, Bled via Orbital for Clin Path, No Ophthalmological Abnormalities Detected Sacrificed by design Right General observation. No Abnormality Detected Eye Observations, Bled via Orbital for Clin Path, No Ophthalmological Abnormalities Detected Sacrificed by design Right General observation. No Abnormality Detected Eye Observations, Bled via Orbital Eye Observations, Bled via Orbital Eye Observations, Bled via Orbital Sacrificed by design for Clin for Clin for Clin Path, Path, Path, Bilateral Left Right 0-42,49-77,84-93 45,93 80 93 0-42,49-77,84-93 45,93 80 93 0,7,14-28,35-49,56-70,77.98,105,112,119,126-133,14 0-3 9,21,96,108,139,160,181 34,55,76,89,92,101,115,12 181 F IV F IV 643411 Eye Observations, Bled via Orbital for Clin Path, Right Comments, ak during bleed Accidentally killed 643379 General observation. No Abnormality Detected Eye Observations, Bled via Orbital for Clin Path, Bilateral " Eye Observations, Bled via Orbital for Clin Path, Left Eye Observations, Bled via Orbital for Clin Path, Right Discharge, Eye right. Black Discharge, Eye right. Brown Sacrificed by design 0,7,14-28,35-49,56-70,7798,105,126,147-154,161-18 101,108,115,125 3,9,21,96,139,160,181 0,34,55,76,89,92 112,119 133,140 181 P IV 643391 General observation. No Abnormality Detected Eye Observations, Bled via Orbital for Clin Path, Eye Observations, Bled via Orbital for Clin Path, Hair Loss, Nose Wound, Superficial, Nose Sacrificed by design Left Right 0,7,49,56-70,77-84,91,98,1 126-133,140-154,161-181 3,9,21,96,108,139,160,181 0,34,55,76,89,92,101,115,1 21-28,35-42 14 181 F IV 643437 General observation. No Abnormality Detected Eye Observations, Bled via Orbital for Clin Path, Left Eye Observations, Bled via Orbital for Clin Path, Right Sacrificed by design 0,7,14-28,35-49,56-70,7798,105,112,119,126-133,14 3,9,21,96,108,139,160,181 0,34,55,76,89,92,101,115, 181 F IV 643399 General observation. No Abnormality Detected Removed from study 0-74 74 659 H-24516: Subchronic Toxicity 90-Day Gavage Study in Rats with One-Generation Reproduction Evaluations Sex Group Animal F IV 643334 F IV 643464 P IV 643369 F IV 643490 P IV 643342 F IV F IV 643438 643445 ^ F IV w a F IV 3 S N <&S F IV S F a IV S & F IV S F IV 5> 3 g-4. w F IV v 0CD F IV 643418 643325 643479 643403 643376 643422 643452 643475 INDIVIDUAL CLINICAL AND OPH'rHALMOLOGICAL OBS:ERVATIONS AND MORTALITY D Observation Days General observation, No Abnormality Detected Removed from study 0-74 74 General observation. No Abnormality Detected Removed from study 0-74 74 General observation, No Abnormality Detected Removed from study 0-74 74 General observation. No Abnormality Detected Removed from study 0-74 74 General observation, No Abnormality Detected Hair Loss, Forepaw, Bilateral Hair Loss, Forepaw, Right Removed from study 0-14 21-56 63-74 74 General observation. No Abnormality Detected Removed from study 0-74 74 General observation, No Abnormality Detected Comments, compound evident on mouth Removed from study 0-70,74 73 74 General observation, No Abnormality Detected Removed from study 0-74 74 General observation. No Abnormality Detected Removed from study 0-74 74 General observation, No Abnormality Detected Removed from study 0-74 74 General observation. No Abnormality Detected Removed from study 0-74 74 General observation. No Abnormality Detected Removed from study 0-74 74 General observation, Mo Abnormality Detected Removed from study 0-74 74 General observation. No Abnormality Detected Removed from study 0-74 74 General observation. No Abnormality Detected Removed from study 0-74 74 660 H-24516: Subchronic Toxicity 90-Day Gavage Study in Rats with One-Generation Reproduction Evaluations Sex Group Animal P IV 643372 F IV 643400 F IV 643395 P IV 643457 INDIVIDUAL CLINICAL AND OPHTHALMOLOGICAL OBSERVATIONS AND MORTALITY DA Observation Days General observation, No Abnormality Detected Removed from study 0-74 74 General observation. No Abnormality Detected Removed from study 0-74 74 General observation. No Abnormality Detected Removed from study 0-74 74 General observation. No Abnormality Detected Removed from study 0-74 74 661 H-24516: Subchronic Toxicity 90-Day Gavage Study in Rats with One-Generation Reproduction Evaluations Sex Group Animal F VI 643322 F VI 643489 F VI 643409 F VI 643366 F VI 643367 F VI 643461 F VI 643462 F VI 643392 F VI 643472 INDIVIDUAL CLINICAL AND OPHTHALMOLOGICAL OBSERVATIONS AND MORTALITY DA Observation Days General observation, Mo Abnormality Detected Eye Observations, Bled via Orbital for Clin Path, No Ophthalmological Abnormalities Detected Sacrificed by design Right 0-42,49-77,84-91,93 45,92-93 80 93 General observation. No Abnormality.Detected Eye Observations. Bled via Orbital for Clin Path, No Ophthalmological Abnormalities Detected Sacrificed by design Right General observation. No Abnormality Detected Eye Observations, Bled via Orbital for Clin Path, No Ophthalmological Abnormalities Detected Sacrificed by design Right 0-42,49-77,84-93 45,93 80 93 0-42,49-77,84-93 .45,93 80 93 General observation. No Abnormality Detected Eye Observations, Bled via Orbital for Clin Path, No Ophthalinological Abnormalities Detected Sacrificed by design Right General observation, No Abnormality Detected Eye Observations, Bled via Orbital for Clin Path, No Ophthalmological Abnormalities Detected Sacrificed by design Right 0-42,49-77,84-93 45,93 80 93 0-42,49-77,84-93 45,93 80 93 General observation. No Abnormality Detected Eye Observations, Bled via Orbital for Clin Path, Eye Observations, Bled via Orbital for Clin Path, Retina, Retinal Degeneration Diffuse, Left Sacrificed by design Bilateral Right 0-42,49-77,84-93 93 . 45 80 93 General observation. No Abnormality Detected Eye Observations, Bled via Orbital for Clin Path, No Ophthalmological Abnormalities Detected Sacrificed by design Right 0-42,49-77,84-93 45,93 80 93 General observation, No Abnormality Detected Eye Observations, Bled via Orbital for Clin Path, No Ophthalmological Abnormalities Detected Sacrificed by design Right General observation. No Abnormality Detected Eye Observations, Bled via Orbital for Clin Path, No Ophthalmological Abnormalities Detected Sacrificed by design Right 0-42,49-77,84-93 45,93 80 93 0-42,49-77,84-93 45,93 80 93 662 H-24516: Subchronic Toxicity 90-Day Gavage Study in Rats with One-Generation Reproduction Evaluations Sex Group Animal F VI 643323 F VI 643412 F VI 643382 F VI 643381 P VI 643360 INDIVIDUAL CLINICAL AND OPHTHALMOLOGICAL OBSERVATIONS AND MORTALITY DA Observation General observation. No Abnormality Detected Eye Observations, Bled via Orbital for Clin Path, No Ophthalmological Abnormalities Detected Comments, protective gavage ball fell off predose Sacrificed by design Right Days 0-28,35-42,49-77,84-93 45,93 80 34 93 General observation. No Abnormality Detected Eye Observations, Bled via Orbital for Clin Path, Bilateral Eye Observations, Bled via Orbital for Clin Path, Left Eye Observations, Bled via Orbital for Clin Path, Right Sacrificed by design 0,7,14-28,35-49,56-70,77-8 98,105,112,119,126-133,140 181 3,9,21,96,108,139,160 0,34,55,76,89,92,101,115,1 181 General observation. No Abnormality Detected Eye Observations, Partially Closed, Left Eye Observations, Enophthalmus, Left Eye Observations, Exophthalmus, Left Eye Observations, Bled via Orbital for Clin Path, Left Eye Observations, Bled via Orbital for Clin Path, Right Eye Observations, Corneal Opacity, Left General Teeth Observations, Discharge, Eye left. Black Wound, Superficial, Mouth Sacrificed by design Clipped 0,7,14-21 112,119,126-133,140-154,16 49,56-70,77-84,91,98,105,1 126-133,140-154,161-181 28,35-42 3,9,21,115 0,34,55,76,89,92-96,101,10 181 35-49,56-70,77-84,91,98,10 119,126-133,140-154,161-18 126-133,140-154,161-181 28,35 63 181 General observation. No Abnormality Detected Eye Observations, Bled via Orbital for Clin Path, Left Eye Observations, Bled via Orbital for Clin Path, Right Sacrificed by design General observation. No Abnormality Detected Eye Observations, Exophthalmus, Left Eye Observations, Exophthalmus, Right Eye Observations, Bled via Orbital for Clin Path, Eye Observations, Bled via Orbital for Clin Path, Eye Observations, Bled via Orbital for Clin Path, Eye Observations, Corneal Opacity, Left General Teeth Observations, Clipped Discharge, Nose, Black Discharge, Eye left. Black Sacrificed by design Bilateral Left Right 0,7,14-28,35-49,56-70,77-8 98,105,112,119,126-133,140 3,9,21,96,108,139,160,181 0,34,55,76,89,92,101,115,1 181 0,7,14-28,35-49,56-70,77-8 98,105,112,119,126 91 89,92,108,115 3,9,21,96,139,160,181 0,34,55,76,101,125 98,105,112,119,126-133,14 161-181 119 : 98,105,112 181 663 H-24516: Subchronic Toxicity 90-Day Gavage Study in Rats with One-Generation Reproduction Evaluations INDIVIDUAL CLINICAL AND OPHTHALMOLOGICAL OBSERVATIONS AND MORTALITY DA Sex Group Animal Observation Days F VI 643373 General observation, No Abnormality Detected Eye Observations, Exophthalmua, Bilateral Eye Observations, Exophthalmua, Left Eye Observations, Eye Observations, Eye Observations, Eye Observations, Eye Observations, Exophthalmua, Right Bled via Orbital for Clin Path, Bled via Orbital for Clin Path, Bled via Orbital for Clin Path, Corneal Opacity, Bilateral Bilateral Left Right Eye Observations, Corneal Opacity, Right Discharge, Eye right. Black Sacrificed by design 0,7,14-28 56-70 77-84,91,98,105,112,119,1 140-154,161-181 35-49 0,55,76,89,92,108,115 3,9,21,96,139 34,101,125,160,181 56-70,77-84,91,98,105,112 140-154,161-181 35-49 35 181 F VI 643320 General observation. No Abnormality Detected Removed from study 0-74 74 F VI 643488 General observation, No Abnormality Detected Removed from study 0-74 74 F VI 643428 General observation. No Abnormality Detected Removed from study 0-74 74 F VI 643439 General observation. No Abnormality Detected Removed from study 0-74 74 F VI 643353 General observation. No Abnormality Detected Removed from study 0-74 74 F VI 643385 General observation. No Abnormality Detected Removed from study 0-74 74 F VI 643339 General observation. No Abnormality Detected Removed from study 0-74 74 P VI 643473 General observation. No Abnormality Detected Removed from study 0-74 74 F VI 643337 General observation. No Abnormality Detected Removed from study 0-74 74 F VI 643416 General observation. No Abnormality Detected Removed from study 0-74 74 F VI 643407 General observation, No Abnormality Detected Hair Loss, Forelimb, Right Comments, compound evident on lips Removed from study 0-28,36-42 49-74 35 74 664 H-24516: Subchronic Toxicity 90-Day Gavage Study in Rats with One-Generation Reproduction Evaluations Sex Group Animal F VI 643357 P VI 643331 F VI 643427 F VI 643470 P VI 643434 F VI 643349 P VI F VI F VI 643454 643333 643460 INDIVIDUAL CLINICAL AND OPHTHALMOLOGICAL OBSERVATIONS AND MORTALITY DA Observation Days General observation, Mo Abnormality Detected Removed from study 0-74 74 General observation. No Abnormality Detected Removed from study 0-74 74 General observation. No Abnormality Detected Removed from study 0-74 74 General observation, No Abnormality Detected Removed from study 0-74 74 General observation. No Abnormality Detected Removed from study 0-74 74 General observation. No Abnormality Detected Hair Loss, Forepaw, Bilateral Removed from study 0-21,74 28-70 74 General observation. No Abnormality Detected Removed from study 0-74 74 General observation, No Abnormality Detected Removed from study 0-74 74 General observation, No Abnormality Detected Removed from study 0-74 74 665 H-24516: Subchronic Toxicity 90-Day Gavage Study in Rats with One-Generation Reproduction Evaluations Sex Group Animal P VIII 643341 F VIII 643370 F VIII 643446 F VIII 643435 F VIII 643466 F VIII 643332 F VIII 643404 INDIVIDUAL CLINICAL AND OPHTHALMOLOGICAL OBSERVATIONS AND MORTALITY DA Observation Days General observation. No Abnormality Detected Eye Observations, Bled via Orbital for Clin Path, General Teeth Observations, Clipped No Ophthalmological Abnormalities Detected Sacrificed by design Right 0-42,49-70 45,92-93 76-77,84-91,93 80 93 General observation, No Abnormality Detected Eye Observations, Bled via Orbital for Clin Path, General Teeth Observations, Clipped No Ophthalmological Abnormalities Detected Sacrificed by design Right 0-42,49-63 45,93 65-77,84-93 80 93 General observation. No Abnormality Detected Eye Observations, Bled via Orbital for Clin Path, General Teeth Observations, Clipped No Ophthalmological Abnormalities Detected Sacrificed by design Right 0-42,49-56 45,93 63-77,84-93 80 93 General observation, No Abnormality Detected Eye Observations, Bled via Orbital for Clin Path, General Teeth Observations, Clipped Hyperactive Hyperreactive No Ophthalmological Abnormalities Detected Sacrificed by design Right 0-42,49-63 45,93 84-93 70-77,84-93 70-77,84-93 80 93 General observation. No Abnormality Detected Eye Observations, Bled via Orbital for Clin Path, General Teeth Observations, Clipped No Ophthalmological Abnormalities Detected Sacrificed by design Right 0-42,49-77 45,93 84-93 80 93 General observation. No Abnormality Detected Eye Observations, Bled via Orbital for Clin Path, General Teeth Observations, Clipped No Ophthalmological Abnormalities Detected Sacrificed by design Right 0-42,49-56 45,93 63-77,84-93 80 93 General observation. No Abnormality Detected Eye Observations, Bled via Orbital for Clin Path, General Teeth Observations, Clipped No Ophthalmological Abnormalities Detected Sacrificed by design Right 0-42,49-77 45,93 84-93 80 93 666 H-24516: Subchronic Toxicity 90-Day Gavage Study in Rats with One-Generation Reproduction Evaluations Sex Group Animal F VIII 643408 F VIII 643359 F VIII 643340 F VIII 643487 P VIII 643356 INDIVIDUAL CLINICAL AND OPHTHALMOLOGICAL OBSERVATIONS AND MORTALITY DA Observation Days General observation. No Abnormality Detected Eye Observations, Bled via Orbital for Clin Path, General Teeth Observations, Clipped No Ophthalmological Abnormalities Detected Sacrificed by design Right 0-42,49-63 45,93 70-77,84-93 80 93 General observation. No Abnormality Detected Eye Observations, Bled via Orbital for Clin Path, No Ophthalmological Abnormalities Detected Sacrificed by design Right 0-42,49-77,84-93 45,93 80 93 General observation. No Abnormality Detected Eye Observations, Bled via Orbital for Clin Path, Hair Loss, Forepaw, Bilateral Found dead in cage. Right General observation. No Abnormality Detected Eye Observations, Exophthalmus, Right Eye Observations Bled via Orbital for Clin Path, Eye Observations Bled via Orbital for Clin Path, Eye Observations Bled via Orbital for Clin Path, Eye Observations Corneal Opacity, Right Bilateral Left Right General Teeth Observations, Clipped Sacrificed by design General observation. No Abnormality Detected Eye Observations Partially Closed, Left Eye Observations Enophthalmus, Bilateral Eye Observations Exophthalmus, Left Eye Observations Exophthalmus, Right Eye Observations Bled via Orbital for Clin Path, Eye Observations Bled via Orbital for Clin Path, Eye Observations Bled via Orbital for Clin Path, Bilateral Left Right Eye Observations, Corneal Opacity, Left General Teeth Observations, Clipped Breathing Observations, Noise Discharge, Eye left. Black Discharge, Eye right. Black Hair Loss, Pace, Right Comments, compound evident on mouth Sacrificed by design 0-14 45 21-42,49-69 69 0,7,14-28,35-49,56-70 77-84 76,89,92 3,9,21,96,108,139,160,181 0,34,55,101,115,125 77-84,91,98,105,112,119,1 140-154,161-181 80,119,126-133,140-154,16 181 0,7,14-28 112,119,126-133,140-154,1 181 35-49 161-175 21,34 3,9 0,55,76,89,92-96,101,108, 181 35-49,56-84,91,98,105,112 105,112,119,126-133,140-1 140-154,161-175 35,98,105,112,119 161-175 49 76 181 667 H-24516: Subchronic Toxicity 90-Day Gavage Study in Rats with One-Generation Reproduction Evaluations Sex Group Animal F VIII 643329 P VIII 643388 F VIII 643450 F VIII 643467 F VIII 643443 F VIII 643417 F VIII 643413 F VIII 643338 INDIVIDUAL CLINICAL AND OPHTHALMOLOGICAL OBSERVATIONS AND MORTALITY DA Observation Days General observation. No Abnormality Detected Eye Observations, Bled via Orbital for Clin Path, Eye Observations, Bled via Orbital for Clin Path, Eye Observations, Bled via Orbital for Clin Path, General Teeth Observations, Clipped Hair Loss, Neck, Dorsal Hair Loss, Nose Sacrificed by design Bilateral Left Right 0,7,42-49,56-70,77-84,91, 101 3,9,21,96,108,139,160,181 0,34,55,76,89,92,115,125 105,112,119,126-133,140-1 14-28,35 14,119,126-133 181 General observation. No Abnormality Detected Eye Observations, Bled via Orbital for Clin Path, Eye Observations, Bled via Orbital for Clin Path, General Teeth Observations, Clipped Left Right Sacrificed by design 0,7,14-28,35-49 3,9,21,96,108,139,160,181 0,34,55,76,89,92,101,115. 54,56-70,77-84,91,98,105 126-133,140-154,161-181 181 General observation. No Abnormality Detected Eye Observations Exophthalmus, Left Eye Observations Bled via Orbital for Clin Eye observations Bled via Orbital for Clin Eye Observations Bled via Orbital for Clin Eye Observations Corneal Opacity, Left General Teeth Observations, Clipped Discharge, Eye left. Black Comments, growth on left eye Sacrificed by design Path, Path, Path, Bilateral Left Right ' 0,7,14-28,35-49,56-70,7798,105,112,119,126-133,14 161-181 108,115 3,9,21,96,139,160 0,34,55,76,89,92,101,125, 168-181 161-181 161 181 181 General observation, No Abnormality Detected General Teeth Observations, Clipped Hair Loss, Hindlimb, Left Hair Loss, Side, Right Removed from study 0-63 70 74 74 74 General observation. No Abnormality Detected Removed from study 0-74 74 General observation. No Abnormality Detected General Teeth Observations, Clipped Removed from study 0-63,74 70 74 General observation. No Abnormality Detected Removed from study 0-74 74 General observation. No Abnormality Detected Removed from study 0-74 74 668 -24516: Subchronic Toxicity 90-Day Gavage Study in Rats with One-Generation Reproduction Evaluations Sex Group Animal F VIII 643335 F VIII 643468 P VIII 643440 P VIII 643430 F VIII 643431 F VIII 643368 F VIII 643326 F VIII 643365 F VIII 643375 INDIVIDUAL CLINICAL AND OPHTHALMOLOGICAL OBSERVATIONS AND MORTALITY DA Observation Days General observation. No Abnormality Detected Removed from study 0-74 74 General observation. No Abnormality General Teeth Observations, Clipped Discharge, Nose, Red Diarrhea, Black Stain Fur/Skin, Face, Brown Removed from study Detected 0-63,74 70 70 70 70 74 General observation, Mo Abnormality Detected General Teeth Observations, Clipped Stain Fur/Skin, Inguen, Yellow Stain Fur/Skin, Face, Brown Removed from study 0-56,74 63-70 70 63-70 74 General observation, No Abnormality Comments, teeth loose General Teeth Observations, Absent General Teeth Observations, Broken Removed from study Detected 0-70 71 71-74 71-74 74 General observation, No Abnormality Detected General Teeth Observations, Clipped Removed from study 0-63 70-74 74 General observation, No Abnormality Detected Eye Observations, Enophthalmus, Bilateral Discharge, Mouth, Tan Dehydrated. Stain Fur/Skin, Perineum, Yellow Wet Fur, Perineum Accidentally Killed 0-42 49-53 47-53 47-53 47-53 47-53 53 General observation, No Abnormality General Teeth Observations, Absent General Teeth Observations, Clipped Discharge, Eye bilateral. Black Discharge, Mouth, Clear Removed from study Detected 0-56,74 63-70 63-70 63 63 74 General observation. No Abnormality Detected Removed from study 0-74 74 General observation, Mo Abnormality Detected General Teeth Observations, Clipped Removed from study 0-70 74 74 669 H-24516: Subchronic Toxicity 90-Day Gavage Study in Rats with One-Generation Reproduction Evaluations Sex Group Animal F VIII 643328 P VIII 643348 F VIII 643346 F VIII 643449 F VIII 643429 F VIII 643424 F VIII 643347 P VIII 643456 F VIII 643423 INDIVIDUAL CLINICAL AND OPHTHALMOLOGICAL OBSERVATIONS AND MORTALITY DA Observation Days General observation. No Abnormality Detected Removed from study 0-74 74 General observation. No Abnormality Detected Removed from study 0-74 74 General observation. No Abnormality Detected Removed from study 0-74 74 General observation. No Abnormality Detected General Teeth Observations, Clipped Removed from study 0-56,74 63-70 74 General observation, No Abnormality General Teeth Observations, Clipped Hair Loss, Forelimb, Bilateral Hair Loss, Hindlimb, Bilateral Hair Loss, Hindlimb, Right Hair Loss, Side, Bilateral Hair Loss, Side, Right Removed from study Detected 0-28 70 42-74 42-74 35 56-74 49 74 General observation, No Abnormality Detected General Teeth Observations, Clipped Removed from study 0-70 74 74 General observation. No Abnormality Detected General Teeth Observations, Clipped No Ophthalmological Abnormalities Detected Sacrificed by design 0-77,84-112 119,125 80,122 125 General observation. No Abnormality Detected General Teeth Observations, Maloccluded General Teeth Observations, Clipped Discharge, Eye right. Red No Ophthalmological Abnormalities Detected Sacrificed by design General observation, No Abnormality Detected Eye Observations, Enophthalmus, Right General Teeth Observations, Clipped No Ophthalmological Abnormalities Detected Mass Abdomen, Mass #2, Not Ulcerated, 1.0 cm Mass Side, Left, Mass #1, Not Ulcerated, 1.5 cm Mass Side, Left, Mass #1, Not Ulcerated, 1 cm. Sacrificed by design 0-49 119,125 54-77,84-119,125 119,125 80,122 125 0-14 21-77,84-119,125 84-119,125 80,122 119,125 112-119,125 64-77,84-105 125 670 H-24516: Subchronic Toxicity 90-Day Gavage Study in Rats with One-Generation Reproduction Evaluations Sex Group Animal F VIII 643345 F VIII 643351 F VIII 643358 F VIII 643444 iF VIII 643474 F VIII 643441 P VIII 643481 INDIVIDUAL CLINICAL AND OPHTHALMOLOGICAL OBSERVATIONS AND MORTALITY D Observation Days General observation. No Abnormality Detected General Teeth Observations, Clipped No Ophthalmol09ical Abnormalities Detected Sacrificed by design 0-49 54-77,84-119,125 80,122 125 General observation. No Abnormality Detected General Teeth Observations, Absent General Teeth Observations, Clipped No Ophthalroological Abnormalities Detected Sacrificed by design 0-56 63-65 65-77,84-119,125 80,122 125 General observation, No Abnormality Detected No Ophthalmological Abnormalities Detected Sacrificed by design General observation. No Abnormality Detected General Teeth Observations, Clipped General Teeth Observations, Clipped, teeth caught in cage No Ophthalmological Abnormalities Detected Stain Fur/Skin, Shoulder, Right, Brown Sacrificed by design General observation, No Abnormality Detected -No Ophthalmological Abnormalities Detected Sacrificed by design General observation. No Abnormality Detected General Teeth Observations, Clipped No Ophthalmological Abnormalities Detected Sacrificed by design 0-77,84-119,125 80,122 125 0-14 105-119,125 73 80,122 21-77,84-112 125 0-77,94-119,125 80,122 125 0-56 63-77,84-119,125 80,122 125 General observation. No Abnormality Detected General Teeth Observations, Clipped No Ophthalmological Abnormalities Detected Sacrificed by design 0-77,84-98 105-119,125 80,122 125 671 H-24516: Subchronic Toxicity 90-Day Gavage Study in Rats with One-Generation Reproduction Evaluations _________DuPont-5386 APPENDIX F OPHTHALMOLOGY EXAMINATION REPORTS 672 ^ESp-asy^.^*;^ n-^-tj iu. ijiiiA.uiumu luxiciiy 90-Day Gavage Study in Rats with One-Generation Reproduction Evaluations_________DuPont-5386 OPHTHALMOLOGICAL EXAMINATION REPORT (TEST DAY 80) NANCY M. BROMBERG, VALD., MJS. EYE CLINIC FOR ANIMALS 6119 MASSACHUSETTS AVE BETHESDA, MD 20816 STUDY INFORMATION; Study No Specie: 1 Study Director; GregLadira OPHTHALMOLOGICAL EXAMINATION SUMMARY Examination Date: March 2,2001 METHODS: Indirect Ophthilmoscopy following 1% Tropicamide mydriasis Sex Gronp# Cage# Animal # Observation Female VI 606 643461 Diffuse retinal degeneration OS COMMENTS/DISCUSSION One female was identified with retinal degeneration which may be due to trauma to the orbit and/or globe doriag orbital maus bleeding. AB other animals exammed bad no visible ophthahnogcopic lesions. No compound related abnormalities were identified. ^Wi^^^^/ 673 ^gmpany SanRteed. Ooes not contain TSCA CBI OPHTHALMOLOGICAL EXAMINATION REPORT (TEST DAY 122) NANCY M. BROMBERG, VALD., M.S, DA.C.V.O. EYE CLINIC TOR ANIMALS 6119 MASSACHUSETTS AVE BETHESDA,MD 20816 STUDY INFORMATION; Study No Species: 1 SfaSyDireetonGr^l Ladies OPHTHALMOLOGICAL EXAMINATION SUMMARY EniDination Date: April 13,2001 METHODS: Indirect Ophthalmoscopy following 1% Tropicamide mydriasis COMMENTSYDISCUSSION All aaunab examined had no visible ophthahnoscopic lesions. <3^j2/^i^/ Date 674 Company Sanitized. Does not contain TSCA CBI APPENDIX G INDIVIDUAL FORELIMB GRIP STRENGTH AND HINDLIMB GRIP STRENGTH 675 g5eapanySanitized. Does not contain TSCA CBI H-24516: Subchronic Toxicity 90-Day Gavage Study in Rats with One-Generation Reproductive Evaluations INDIV 1DUALFOBLELIMB GR][P STRENGTH A ND HINDU MB GRIP STRENGTH Baseline Male Rats/Groiup I O nig/kg/.day ]Forelimb Grip Strength ft^ Animal Number 643162 643172 643195 643226 643237 643246 643253 643262 " 643303 643304 Trial 1 0.52 0.51 0.60 0.56 0.36 0.39 0.52 0.52 0.49 0.40 Trial 2 0.51 0.83 0.57 0.65 0.29 0.48 0.48 0.60 0.56 0.44 TrialS 0.59 0.55 0.35 0.60 0.48 0.48 0.58 0.59 0.51 0.38 Mean of Three Trials 0.54 0.63 0.51 0.60 0.38 0.45 0.53 0.57 0.52 0.41 Hindlimb ( jrip Strengthi(kR Trial 1 Trial 2 Trial 3 T 0.45 0.37 0.43 0.31 0.39 0.45 0.40 0.38 0.42 0.36 0.39 0.28 0.58 0.34 0.51 0.32 0.53 0.30 0.34 0.39 0.52 0.51 0.47 0.59 0.37 0.39 0.33 0.23 0.43 0.30 676 Company Sanitized. Does BOc H-24516: Subchronic Toxicity 90-Day Gavage Study in Rats with One-Generation Reproductive Evaluations INDI VIDUAL FOBLELIMB GIUP STRENGTH A ND HINDLIMBGRIPSTRENGTH Baseline Male Rats/Gro up III 25 m^S/kg/day Animal Number 643173 643179 643180 643228 643240 643264 643272 643290 643292' 643308 Trial 1 0.60 0.42 0.45 0.83 0.52 0.59 0.38 0.31 0.50 0.46 Forelimb Grip Streneth( kR) Trial 2 Trial 3 Mean of Three Trials 0.53 0.43 0.52000 0.33 0.64 0.46333 0.48 0.56 0.49667 0.77 0.72 0.77333 0.46 0.67 0.55000 0.66 0.41 0.55333 0.36 0.55 0.43000 0.60 0.45 0.45333 0.63 0.63 0.58667 0.38 0.39 0.41000 Hindlimb (3rip Strength>(kR Trial 1 Trial 2 Trial 3 T 0.48 0.42 0.42 0.43 0.40 0.50 0.37 0.47 0.56 0.27 0.26 0.39 0.27 0.26 0.24 0.32 0.39 0.37 0.37 0.42 0.39 0.40 0.39 0.45 0.31 0.30 0.31 0.59 0.38 0.33 677 Company Sanitized. Does not con ft H-24516: Subchronic Toxicity 90-Day Gavage Study in Rats with One-Generation Reproductive Evaluations IND][VIDUAL FOEIELIMBGIUP STRENGTH A ND HINDL1;MB GRIP SlRENGTH Baseline Male Rats/GroiJpV 100 irig/kg/day Forelimb Grip Strength ( kR) Animal Number 643175 643224 643243 643247 643250 643257 643275 643311 " 643314 643318 Trial 1 0.50 0.57 0.47 0.71 0.64 0.56 0.59 0.74 0.64 0.53 Trial 2 0.65 0.42 0.37 0.50 0.51 0.48 0.70 0.47 0.60 0.41 Trial3 0.41 0.44 0.37 0.80 0.46 0.48 0.54 0.55 0.56 0.38 Mean of Three Trials 0.52 0.48 0.40 0.67 0.54 0.51 0.61 0.59 0.60 0.44 Hindlimb ( jrip Strength(ke) Trial 1 Trial 2 Trial 3 T 0.43 0.30 0.35 0.23 0.47 0.28 0.32 0.39 0.30 0.26 0.29 0.39 0.32 0.26 0.39 0.38 0.32 0.43 0.42 0.32 0.40 0.30 0.37 0.35 0.37 0.43 0.46 0.35 0.45 0.32 678 .Company Sanitized. Does nui cu H-24516: Subchronic Toxicity 90-Day Gavage Study in Rats with One-Generation Reproductive Evaluations INDI VIDUAL FOEIELIMB GfHP STRENGTH A ND HINDLI MB GRIP Sl'RENGTH Baseline Male Rats/Gro up VII 2501mg/kg/day Animal Number 643151 643165 643220 643225 643234 643236 643258 643266 643296" 643316 Trial 1 0.66 0.48 0.70 0.56 0.60 0.54 0.53 0.33 0.66 0.56 Forelimb Gri D Strength ( kR) Trial 2 Trial 3 Mean of Three Trials 0.55 0.76 0.66 0.54 0.46 0.50 0.67 0.53 0.63 0.46 0.56 0.53 0.47 0.54 0.54 0.48 0.51 0.51 0.58 0.46 0.52 0.38 0.44 0.38 0.76 0.61 0.68 0.46 0.46 0.49 Hindlimb (3rip Strength.(k Trial 1 0.49 0.33 0.50 0.29 0.33 0.31 0.49 0.36 0.59 0.26 Trial 2 0.31 0.34 0.40 0.43 0.43 0.38 0.30 0.44 0.41 0.27 Trial 3 0.46 0.30 0.27 0.66 0.34 0.60 0.43 0.44 0.45 0.38 679 Company Sanitized. Does no H-24516: Subchronic Toxicity 90-Day Gavage Study in Rats with One-Generation Reproductive Evaluations INDIVIDUAL FORELIMB GRIP STRENGTH AND HINDLIMB GRIP STRENGTH Baseline Female Rats/Group II 0 mg/kg/day Forelimb Grip Strength (kg) Animal Number 643330 643336 643377 643387 643405 643415 643425 643426 643448 643453 Trial 1 0.28 0.60 0.47 0.51 0.51 0.54 0.47 0.37 0.59 0.62 Trial 2 0.71 0.46 0.77 0.62 0.76 0.68 0.47 0.47 0.80 0.76 Triiaall33 0.57 0.45 0.67 0.88 0.55 0.55 0.61 0.54 0.61 0.63 Mean of Three Trials 0.52 0.50 0.64 0.67 0.61 0.59 0.52 0.46 0.67 0.67 Hindlimb Grip Strength (kg) Trial 1 Trial 2 Trial 3 Th 0.42 0.33 0.32 0.34 0.43 0.53 0.45 0.42 0.37 0.38 0.41 0.37 0.27 0.32 0.23 0.31 0.48 0.30 0.37 0.40 0.38 0.38 0.40 0.35 0.41 0.41 0.31 0.34 0.34 0.41 680 Company Sanitized. Does n H-24516: Subchronic Toxicity 90-Day Gavage Study in Rats with One-Generation Reproductive Evaluations INDI VIDUALFOB.ELIMB GEUP STRENGTH A ND HINDLI MB GRIP SIRENGTH Baseline Female Rats/Gi-oup IV 25 iTig/kg/day Animal Number 643321 643324 643364 643380 643389 643390 643396 643410 " 643433 643458 Trial 1 0.74 0.46 0.37 0.43 0.43 0.74 0.47 0.33 0.42 0.62 Forelimb Grip Strength ( kg) Trial 2 Trial 3 Mean of Three Trials 0.60 0.51 0.62 0.63 0.56 0.55 0.40 0.53 0.43 0.56 0.56 0.52 0.31 0.43 0.39 0.76 0.73 0.74 0.66 0.72 0.62 0.30 0.50 0.38 0.65 0.47 0.51 0.74 0.56 0.64 Hindlimb (3rip Strength>(kR) Trial 1 Trial 2 Trial 3 Th 0.35 0.38 0.26 0.33 0.40 0.38 0.44 0.43 0.50 0.44 0.61 0.43 0.35 0.39 0.30 0.57 0.37 0.37 0.34 0.45 0.36 0.33 0.32 0.27 0.44 0.35 0.40 0.39 0.29 0.35 681 Company Sanitized. Does no H-24516: Subchronic Toxicity 90-Day Gavage Study in Rats with One-Generation Reproductive Evaluations IND]VIDUAL FOl^ELIMB GR][P STRENGTH.AND HINDL1MB GRIP STRENGTH Baseline Female Rats/Gr oupVI 10() mg/kg/day Forelimb Grio Strength (k:R) Animal Number Trial 1 Trial 2 Trial 3 Mean of Three Trials 643322 643323 643366 643367 643392 643409 643461 643462 " 643472 643489 0.59 0.31 0.80 0.30 0.48 0.51 0.61 0.36 0.50 0.56 0.65 0.43 0.70 0.38 0.37 0.61 0.44 0.63 0.42 0.55 0.79 0.52 0.68 0.28 0.62 0.77 0.40 0.71 0.51 0.60 0.68 0.42 0.73 0.32 0.49 0.63 0.48 0.57 0.48 0.57 Hindlimb Cirio Strength ifkR Trial 1 Trial 2 Trial 3 T 0.43 0.29 0.41 . 0.32 0.30 0.30 0.49 0.34 0.41 0.36 0.35 0.32 0.36 0.27 0.32 0.30 0.36 0.30 0.42 0.35 0.27 0.31 0.27 0.41 0.33 0.49 0.37 0.50 0.36 0.37 682 Company Sanitized. Do H-24516: Subchronic Toxicity 90-Day Gavage Study in Rats with One-Generation Reproductive Evaluations INDJ[VIDUAL FOFIELIMB GRJP STRENGTH A ND HINDL1MB GRIP S1'RENGTH Baseline Female Rats/G roupVIII 2 50 mg/kg/day F orelimb Gri p Strength (}kR) Animal Number 643345 643347 643351 643358 643423 643441 643444 643456 643474 643481 Trial 1 0.39 0.76 0.87 0.56 0.33 0.66 0.57 0.59 0.45 0.56 Trial 2 0.56 0.86 0.77 0.41 0.48 0.42 0.67 0.77 0.52 0.86 Trial 3 0.60 0.77 0.76 0.56 0.37 0.43 0.53 0.88 0.46 0.42 Mean of Three Trials 0.52 0.80 0.80 0.51 0.39 0.50 0.59 0.75 0.48 0.61 Hindlimb (3rip Strenetli(kR) Trial 1 Trial 2 Trial 3 T 0.28 0.40 0.35 0.45 0.51 0.27: 0.26 0.36 0.39 0.42 0.34 0.31 0.33 0.36 0.41 0.30 0.37 0.37 0.44 0.32 0.41 0.29 0.25 0.31 0.34 0.41 0.37 0.30 0.35 0.38 683 Company Sanitized. Does not con H-24516: Subchronic Toxicity 90-Day Gavage Study in Rats with One-Generation Reproductive Evaluations INDIVIDUAL F01RELIMB GRIP STRENGTH .AND HINDL1MB GRIP STRENGTH Week 13 Male Rats/Groiip I O me/kg/iday Animal Number 643162 643172 643195 643226 643237 643246 643253 643262 " 643303 643304 Trial 1 1.44 1.39 1.60 2.29 0.87 0.80 1.48 1.43 1.65 0.84 ]Forelimb Grip Strength ft:R) Trial 2 Trial 3 Mean of Three Trials 0.99 0.99 1.14 1.73 1.63 1.58 1.18 1.51 1.43 1.33 1.64 1.75 1.05 0.94 0.95 0.96 0.69 0.82 1.46 2.10 1.68 2.32 1.20 1.65 1.69 1.59 1.64 1.54 1.17 1.18 Hindlimb Cirio Strength fke) Trial 1 Trial 2 Trial 3 Th 0.89 0.71 0.86 1.01 0.65 0.78 0.95 0.80 0.98 0.90 1.01 0.90 0.61 0.85 0.83 0.69 0.59 0.51 0.83 1.14 0.87 1.04 1.20 0.91 1.04 0.96 0.80 0.63 0.61 0.62 684 Company Sanitized. Does not contai H-24516: Subchronic Toxicity 90-Day Gavage Study in Rats with One-Generation Reproductive Evaluations IND1[VIDUAL FORELIMBGR][P STRENGTH A ND HINDL11MB GRIP ST'RENGTH Week 13 Male Rats/GroiLip III 25 m,g/kg/day Forelimb Grit) Streneth Cl:(R) Animal Number 643173 Trial 1 1.98 Trial 2 1.44 Trial 3 1.78 Mean of Three Trials 1.73 643179 643180 643228 643240 643264 643272 643290 643292" 643308 0.64 1.49 1.76 1.60 0.74 1.50 1.35 1.15 1.54 1.01 1.64 1.92 1.35 1.48 1.05 0.92 1.12 2.09 1.09 1.28 1.14 1.03 0.97 1.01 1.24 1.40 1.72 0.91 1.47 1.61 1.33 1.06 1.19 1.17 1.22 1.78 Hindlimb (jrip Strength^kR) Trial 1 Trial 2 Trial 3 Th 0.68 0.78 0.68 1.00 0.95 0.79 0.71 0.71 0.86 0.94 0.67 0.86 0.70 0.75 0.82 0.90 0.75 0.77 0.80 0.61 0.70 0.88 0.69 0.97 0.74 0.97 0.93 0.99 0.69 0.82 685 Company Sanitized. Does not conta H-24516: Subchronic Toxicity 90-Day Gavage Study in Rats with One-Generation Reproductive Evaluations IND1VIDUAL FOBLELIMB GRIP STRENGT'H AND HINDLI1S1B GRIP ST.RENGTH Week 13 Male Rats/Group V 100 m ig/kg/day Animal Number 643175 a 643224 643243 643247 643250 643257 643275 643311 " 643314 643318 Trial 1 Forelimb Grip Strength (1<e) Trial 2 Trial 3 Mean of Three Trials 1.24 0.76 11.43 11.64 11.33 ]1.99 11.64 1.99 1.77 0.70 1.03 1.48 1.54 1.49 0.92 1.95 1.73 1.43 0.57 1.25 1.18 1.98 1.03 1.05 0.82 1.81 1.39 0.84 1.01 1.36 1.72 1.28 1.32 1.47 1.84 . 1.53 Hindlimb Girio Strength ifkR) Trial 1 Trial 2 Trial 3 Th 0.67 0.80 0.76 0.87 0.63 0.77 0.67 0.77 0.74 0.80 0.75 0.97 1.07 1.17 0.76 0.51 0.81 0.74 0.66 0.61 0.87 1.29 0.63 0.95 0.65 0.76 0.89 1 Sacrificed in extremis prior to evaluation. 686 Company Sanitized. Does not conta H-24516: Subchronic Toxicity 90-Day Gavage Study in Rats with One-Generation Reproductive Evaluations INDI VIDUAL FOI^ELIMB GRIP STRENGTH.AND HINDLIMIiGRIPSTRENGTH Week 13 Male Rats/Gro up VII 2501ng/kg/day Animal Number 643151 643165 643220 643225 643234 643236 643258 643266 643296" Trial 1 1.32 0.75 1.15 1.73 1.42 1.54 0.91 0.98 1.49 Forelimb Grip Strength C^l Trial 2 Trial 3 Mean of Three Trials 1.31 1.33 1.32 1.62 1.59 1.32 1.01 0.63 0.93 1.63 1.34 1.22 1.65 1.86 1.25 1.03 1.21 1.74 11.34 11.26 11.26 1.00 . 1.33 1.04 1.85 11.01 11.56 643316 1.58 1.22 1.21 ]1.34 I-lindlimb ( 3riD Strength Ckl Trial 1 0.56 0.56 0.84 0.70 0.61 0.61 0.69 0.71 0.97 0.85 Trial 2 0.74 0.61 0.70 0.70 0.78 0.74 0.92 0.53 0.77 0.99 Trial 3 0.81 0.50 0.76 0.76 0.78 0.65 1.10 0.61 0.73 0.74 687 Company Sanitized. Does not co H-24516: Subchronic Toxicity 90-Day Gavage Study in Rats with One-Generation Reproductive Evaluations INDIV][DUAL FOBUELIMB GIUP STRENGTH A ND HINDL][MB GRIP STRENGTH Week 13 Female Rats/G)roup II 0 nig/I:g/day Animal Number 643330 643336 643377 643387 643405 643415 643425 643426 " 64344"8 643453 Trial 1 0.93 1.12 1.16 1.17 1.05 1.13 1.42 1.10 1.16 1.84 I welimb Grip Strength ( kp) Trial 2 Trial 3 Mean of Three Trials 1.00 0.94 0.96 1.37 1.27 1.25 1.63 1.45 1.41 0.69 0.96 0.94 1.31 1.19 1.18 0.97 0.64 0.91 1.23 1.20 1.28 0.90 1.05 1.02 1.41 0.92 1.16 1.48 1.80 1.71 Hindlimb (3rip Strength'(kg Trial 1 Trial 2 Trial 3 T 0.66 0.91 0.85 0.55 0.66 0.50 0.58 0.91 0.86 0.88 0.74 0.80 0.58 0.53 0.74 0.77 0.65 0.69 0.62 0.62 0.63 0.82 0.92 0.80 0.80 0.83 0.74 0.69 0.79 0.85 688 Company Sanitized. Does not conta H-24516: Subchronic Toxicity 90-Day Gavage Study in Rats with One-Generation Reproductive Evaluations IND1VIDUAL FORELIMB GR1 P STRENGTH .AND HINDL 1MB GRIP STRENGTH Week 13 Female Rats/GroupIV 25 mg/kg/day Animal Number 643321 a Trial 1 Forelimb Grip Streneth (k R) Trial 2 Trial 3 Mean of Three Trials 643324 643364 0.77 0.71 0.95 0.57 11.07 11.39 . 0.93 0.89 643380 643389 643390 643396 643410 " 643433 643458 1.45 1.27 1.64 1.25 1.58 1.12 1.13 1.44 1.13 1.68 1.17 1.48 1.10 1.61 0.90 11.36 11.21 11.05 11.12 11.15 11.53 1.26 1.25 1.51 1.16 1.39 1.12 1.42 Hindlimb ( jrio Streneth (\kg Trial 1 Trial 2 Trial 3 Th 0.59 0.71 0.62 0.73 0.73 0.85 0.71 0.50 0.72 0.45 0.74 0.70 0.82 0.79 1.10 0.90 0.61 0.69 0.53 0.71 0.76 0.67 0.81 0.81 0.81 0.56 0.76 ' Sacrificed in extremis prior to evaluation. 689 Company SanHteed. Doe* no ^^^^^^^^e^h H-24516: Subchronic Toxicity 90-Day Gavage Study in Rats with One-Generation Reproductive Evaluations IND1VIDUAL FORLELIMB GR1IP STRENGTH.WD HINDLBIB GRIP ST]RENGTH Week 13 Female Rats/Or oupVI 10() nig/kg/day Forelimb Gri p Strength fkK) Animal Number 643322 643323 643366 643367 643392 643409 643461 Trial 1 0.74 1.12 1.00 1.19 0.87 1.05 1.02 Trial 2 0.52 0.93 1.62 0.95 11.06 11.31 11.23 Trial 3 0.53 0.64 1.22 0.74 0.75 1.56 1.38 Mean of Three Trials 0.60 0.90 1.28 0.96 0.89 1.31 1.21 643462 643472 " 643489 0.72 1.02 1.05 11.11 11.36 11.18 1.50 0.90 0.80 1.11 1.09 1.01 Hindlimb Gtrip Strength (1kg Trial 1 Trial 2 Trial 3 T 0.42 0.57 0.46 0.56 0.59 0.62 0.75 0.77 0.81 0.69 0.69 0.56 0.45 0.69 0.59 0.50 0.51 0.71 0.62 0.80 0.67 0.75 0.81 0.82 0.55 0.81 0.50 0.70 0.70 0.71 690 Company Sanitized. Does not co H-24516: Subchronic Toxicity 90-Day Gavage Study in Rats with One-Generation Reproductive Evaluations IND1[VIDUAL FOI<ELIMB GR]iP STRENGTH AND HINDLIMf$ GRIP ST RENGTH Week 13 Female Rats/Gioup VIII 2 50 mg/kg/day Animal Number 643345 643347 643351 643358 643423 643441 643444 643456 643474" 643481 Trial 1 0.77 0.84 0.66 0.88 1.08 0.90 1.02 0.77 1.21 1.37 Forelimb Grip Strength fk R) Trial 2 Trial 3 Mean of Three Trials 0.65 0.56 0.66 0.91 0.66 0.80 1.22 0.77 0.88 0.89 0.65 0.81 1.00 1.27 1.12 1.53 0.89 1.11 1.58 1.34 1.31 0.94 0.99 0.90 1.33 1.02 1.19 1.46 1.01 1.28 T-lindlimb GIrip Strength ( kR Trial 1 Trial 2 Trial 3 T 0.75 0.66 0.59 0.64 0.54 0.71 0.69 0.51 0.57 0.67 0.45 0.53 0.58 0.67 0.64 0.66 0.71 0.71 0.84 0.88 0.92 0.34 0.35 0.36 0.54 0.72 0.67 0.98 0.75 0.63 691 ^^.^-- H-24516: Subchronic Toxicity 90-Day Gavage Study in Rats with One-Generation Reproductive Evaluations INDIV IDUAL FOBLELIMBGFHP STRENGTH A ND HINDU MB GRIP ST.'RENGTH Recovery Male Rats/Groiip I O mg/kg/iday 'Forelimb Gri p Strength ( kg) Animal Number 643162 643172 643195 643226 643237 643246 643253 643262 " 643303 643304 Trial 1 1.09 1.26 1.42 1.31 0.69 0.99 1.10 1.83 1.16 1.89 Trial 2 0.78 1.37 1.16 0.82 0.73 0.76 1.22 1.86 1.62 1.04 Trial 3 1.30 1.66 1.67 1.51 0.79 0.81 1.34 1.21 2.08 1.56 Mean of Three Trials 1.06 1.43 1.42 1.21 0.74 0.85 1.22 1.63 1.62 1.50 Hindlimb (jrio Strength>(ks) Trial 1 Trial 2 Trial 3 T 0.74 0.65 0.62 0.65 0.92 0.78 0.61 0.76 0.76 0.64 0.58 0.61 0.64 0.61 0.65 0.66 0.77 0.62 1.47 0.76 1.05 0.72 1.01 0.81 0.70 0.70 0.58 0.67 0.71 0.76 692 Company Sanitized. Does not H-24516: Subchronic Toxicity 90-Day Gavage Study in Rats with One-Generation Reproductive Evaluations IND1[VIDLJAL FO]^ELIMB GRIP STRENGTH .AND HINDL 1MB GRIP ST RENGTH Recovery Male Rats/GroiJpVII 250 nig/kg/day Animal Number 643151 643165 643220 643225 643234 643236 643258 643266 643296 " 643316 Trial 1 1.34 2.05 0.75 0.91 1.58 0.81 0.99 1.21 1.14 0.86 Forelimb GrID Strength (1<R) Trial 2 Trial 3 Mean of Three Trials 0.80 1.30 1.15 1.85 1.45 1.78 0.62 0.73 0.70 0.94 1.22 1.02 0.60 0.55 0.91 0.93 0.75 0.83 1.01 0.86 0.95 0.89 0.77 0.96 1.27 1.55 1.32 0.70 0.55 0.70 Hindlimb G!rip Streneth lfkg) Trial 1 Trial 2 Trial 3 Th 0.71 0.52 0.59 0.66 0.75 0.61 0.90 0.82 0.86 0.89 0.80 0.76 0.65 0.64 0.63 0.85 0.87 0.74 0.63 0.63 0.71 0.84 0.87 0.59 0.97 0.80 0.80 0.77 0.71 0.86 693 Company Sanitized. Does not con H-24516: Subchronic Toxicity 90-Day Gavage Study in Rats with One-Generation Reproductive Evaluations IND1[VIDUAL FOI^ELIMBGRJP STRENGTH.AND HINDLIMIi GRIP S7'RENGTH Recovery Female Rats/Groiipll Om,g/kg/day Forelimb Grip Strength d^R) Animal Number Trial 1 Trial 2 Trial 3 Mean of Three Trials 643330 0.65 0.64 0.55 0.61 643336 a 643377 0.93 0.86 0.98 0.92 643387 1.27 1.43 1.19 1.30 643405 0.98 0.94 1.01 0.98 643415 1.11 1.63 1.61 1.45 643425 1.15 1.51 1.34 1.33 643426 643448 - 0.93 0.83 1.21 0.75 1.16 0.73 1.10 0.77 643453 1.15 0.97 1.35 1.16 1Sindlimb (3rip Strength (,k Trial 1 0.46 0.76 0.80 0.55 0.73 0.73 0.82 0.59 0.93 Trial 2 0.58 ... 0.67 0.72 0.59 0.61 0.65 0.90 0.73 0.59 Trial 3 0.54 0.78 0.76 0.63 0.67 0.70 0.79 0.58 0.69 ' Sacrificed in extremis prior to evaluation. 694 Company Sanitized. Does not cont H-24516: Subchronic Toxicity 90-Day Gavage Study in Rats with One-Generation Reproductive Evaluations INI)I\'IDUAL FOIRELIMB GiRIP STRENGTH.AND HINDU[MB GRIP S1TRENGTH Recovery Female Rats/Oreup VIII 2;50:mg/kg/day Animal Number 643345 643347 643351 643358 643423 643441 643444 643456 643474 . " 643481 Trial 1 0.86 0.65 1.56 0.93 0.73 1.49 1.83 0.86 0.66 1.35 Fbrelimb Grip Strength ( kR) Trial 2 Trial 3 Mean of Three Trials 0.72 0.89 0.82 0.71 0.94 0.77 1.38 0.93 1.29 1.30 1.16 1.13 1.30 0.64 0.89 1.83 1.68 1.67 1.46 1.64 1.64 0.71 1.08 0.88 0.76 1.12 0.85 1.73 1.11 1.40 Trial 1 0.68 0.64 0.57 0.53 0.68 0.66 0.79 0.61 0.48 0.70 Hindlimb (3rip Strength.(kg) Trial 2 Trial 3 Me Thre 0.72 0.72 0.50 0.57 0.62 0.54 0.66 0.68 0.79 0.89 0.75 0.71 0.78 0.81 0.55 0.53 0.56 0.46 0.75 0.87 695 Company Sanitized. Does not co APPENDIX H INDIVIDUAL FUNCTIONAL OBSERVATIONAL BATTERY ASSESSMENT 696 (Company Sanitized. Does not contain TSCA CB1 INDIVIDUAL FUNCTIONAL OBSERVATIONAL BATTERY SCORING SYSTEM APPROACH & TOUCH: AUDITORY STIMULUS: TAIL PINCH: DEFECATION: URINATION: PUPILLARY RESPONSE: MANIPULATIONS IN OPEN FIELD ARENA fFREE ROAMING SPACE) -1 = 0 = 1 = -1 = 0 = 1 = no reaction normal increased reaction (jumps away or attacks) no reaction normal reaction (rat flinches or flicks ear) exaggerated reaction (rat jumps, flips) -1 = 0 = 1 = no response normal (turns toward site) exaggerated response (vocalizations, rapid turning) IN MOTOR ACTIVITY MONITOR 0 = 1 = D = absent present diarrhea 0 = 1 = absent present present absent 697 CompanySanitized. Does not contain TSCA CSt APP AN AU STI TA USPU '"""" RE DE I UR 1 III AP AN 0 sassj gBS 0 ,|CfsSa@0 gte>30 aBsicsig, 0 <sHg SSSSS AIN tessa tesisi'li feBgial* saas "-'"" I'iiBBS' a|l AU o agffl ST TA PU RE g|SiiBpif. DE UR ^ APP AN AU STI TAI PUP RES DEF UR ?o 8 ilill ^ gag ^ ^ ^ i 11 p| ?o ^ pixi w fo ^S^ ^is^ igl SIM ii igg s *l^:i si|N '8^1 jSyN SSa PB $ $|| 1|| l8ia |Bl |I^p|l Sp BB ^sB^8^^JyB8^^B^i ^sH^8^^Ptf8^l8 ^ ilM pa ^ liSi ?o ^ 8|?o ^ ||,?o ^ B| ^ H i -*,. 111 < Ilili ?o ^NBioMi SH tel o isi l|a| |B| ||| Hj d| || |jj K| B! tt t BB IM (! AP 0 ^a.,,0 -a^i0 -a.TM0 -bBiB0 -a190. 0P&B0 --Kag0 -i|s0 -f!Sl0 -gagAi NADU ISS SiBiia ii'llii!! 1^1 Ip .0 Ho| s|3| plal p; || Ss^ M ^! ,,TA o o o o o . Tti^ii;;]^! iljiij^nM;' laWiKi o TtfflippiS BfflNi o o ''--"-"i^HI Btt^ o o ^^1"';^ o o te^."^^ ItN" o o ^vt^yiS iiaSi" o o t3K;;s..Sii i8!iiii o o t?y..uj.! SS|[l| o ^iii!]^!" ^'"tilliS ,,JBi| tSI'sli . SS teAlsa illitii ial a||a| aa l|g 1| IM|iiS siBa MIB HIMipM asiai Ba PU ||t p| o sisi o ipa o SisI o "io;'| o o s<s'|fi o tigia o soa o NiW o Bp^ o |sfa o lisisi o o m|gssg o irtM o Ei;o;i; o o ItsiS o o Ssfa igtsa pKp-td' 0 1- |liiSa 1- " |aS| Jilfa " tel- III 1(1 aa S8ft lH -ffilM<=> ~ ISIB o o igrfS>- - siasi o IIM - ||a|| - fcli iBlffl @|||- ~ |ia n""p ^0 it oIiSi JBSo -fflSJo ^g^ -Btt^ UR INDIVIDUAL FUNCTIONAL OBSERVATIONAL BATTERY ASSESSMENT Female Rats/Group II: 0 mg/kg/day MANIPULATIONS IN MA MONITOR Week 13 Recovery ;SK:!ETMssOTSB^^B8=^a|B^^aiS& Week 13 Recovery i^^-^^^Ei^i^H^'^^^'^^^^^iiS^^?^^^ Week 13 000000 000000 000 :i^a^^^t,!"'ra^S5d!aaKBf^(]^liiaSilMi:i:'!at ' Sacrificed in extremis prior to evaluation. 702 Company Sanitized. Does not contain TSCA CB1  AP Il8Hl AN BSi|AU ST .il;|^i;ljl g l ,,w!!,5a,fi'll TA |BI PU tialM RE DE 1111UR AP AN AU ST TA PU RE DE UR INDIVIDUAL FUNCTIONAL OBSERVATIONAL BATTERY ASSESSMENT Female Rats/Group Vm: 250mg/kg/day MANIPULATIONS IN MA MONITOR Week 13 Recovery Week 13 Recovery a't; Week 13 Recovery Week 13 Recovery 0 000 " Additional observation noted b Additional observation noted - c Additional observation noted - Scratch, right comer of eye. Ptosis. Chromodacryorrhea. 0 1 1 0 0 1 0 1 0 0 0 1 ^^'^si^>;^^sS^]K^S^^f^^^'Ss^ 000 0 _ 1 0 _ 0 1 1 000 705 Company Sanitized. Does not contain APPENDIX I INDIVIDUAL MOTOR ACTIVITY ASSESSMENT: DURATION OF MOVEMENTS 706 Company Sanitized. Does not contain TSCA Cff INDIVTOUALMCH-ORACTIVnFY: DIJRATION <OF MOVEl^IENTS(isec) Baseline Male Rats/Group I: Om;g/kg/day Animal Number Suecessive 10-Minute Intervals 1 2 3 4 5 6 Total 643162 643172 643195 643226 643237 643246 643253 643262 643303 643304 553 485 447 80 19 27 1611 389 209 193 10 6 0 807 397 401 306 291 44 1 1440 492 436 408 360 127 10 1833 500 299 286 319 235 84 1723 401 292 241 306 179 34 1453 443 287 247 212 41 165 1395 365 204 193 66 1 5 834 339 161 234 156 34 10 934 425 359 194 70 17 0 1065 Male Rats/Group ffl: 25 mg/kg/day Animal Number Successive 10-Minute Intervals 1 2 3 4 5 643173 643179 643180 643228 643240 643264 643272 643290 643292 643308 391 252 69 23 0 429 322 331 56 2 391 306 296 5 5 361 282 299 35 5 388 306 171 34 1 486 468 485 259 45 403 245 54 6 1 387 268 172 100 12 487 382 305 160 9 464 454 386 189 26 6 Total 6 741 0 1140 9 1012 0 982 1 901 8 1751 1 710 1 940 20 1363 3 1522 707 Company Sanitized. Does not contain TSCA COS INDIVIDUALMOTO RACTIVTTY: DLJRATION (3F MOVEN1ENTS (isec) Baseline Male Rats/Group V: 100 Dag/kg/day Animal Number Sucoessive 10-Minute Intervals 1 2 3 4 5 6 Total 643175 643224 643243 643247 643250 643257 643275 643311 643314 643318 454 386 370 122 5 3 1340 443 385 344 399 260 258 2089 424 278 257 151 29 4 1143 368 299 153 17 0 2 839 329 241 135 77 1 6 789 366 262 53 5 30 0 716 488 406 76 3 32 183 1188 372 304 277 113 37 53 1156 432 366 113 49 17 11 988 353 292 185 24 6 17 877 Male Rats/Group VH: 250 mg/kg/day Animal Number Successive 10-Minute Intervals 1 2 3 4 5 643151 643165 643220 643225 643234 643236 643258 643266 643296 643316 357 267 213 33 0 454 366 366 239 256 434 271 90 1 0 415 267 232 124 102 405 336 298 195 49 312 309 147 1 38 305 159 129 12 1 375 255 251 107 0 434 361 10 6 26 433 280 41 11 0 6 Total 0 870 120 1801 0 796 24 1164 60 1343 238 1045 6 612 2 990 2 839 5 770 708 Company Sanitized. Does not contain TSCA CBI INDIVIDUAL MOTO:R ACTIVITY: DIJRATIONOF MOVmIENTS(i>ec) Baseline Female Rats/Group n: ocoig/kg/day Animal Number Succ;essive 10-Minute Intervals 1 2 3 4 5 6 Total 643330 643336 643377 643387 643405 643415 643425 643426 643448 643453 389 440 249 27 0 1 1106 384 279 289 221 11 3 1187 316 184 10 181 93 9 793 300 236 133 196 220 20 1105 341 260 254 257 160 42 1314 374 272 47 7 168 27 895 459 419 119 301 189 7 1494 381 257 222 214 208 193 1475 401 388 280 209 25 0 1303 364 305 26 46 230 11 982 Female Rats/Group IV: 25 mg/kg/day Animal Number Successive 10-Minute Intervals 1 2 3 4 5 643321 643324 643364 643380 643389 643390 643396 643410 643433 643458 361 290 261 222 11 371 335 330 298 276 439 287 195 53 0 388 212 189 29 237 384 307 181 268 162 382 160 224 273 164 407 278 282 87 8 415 366 376 111 5 412 289 263 185 215 438 331 193 2 8 6 Total 5 1150 110 1720 8 982 102 1157 32 1334 1 1204 50 1112 0 1273 7 1371 7 979 709 Company Sanitized. Does not contain TSCA CBt INDIVIDUAL MOTORACTIVITY: DLJRATION <3F MOVEM]ENTS (s>ec) Baseline Female Rats/Group VI: 100 mg/kg/day Animal Number Successive 10-Minute Intervals 1 2 3 4 5 6 Total 643322 643323 643366 643367 643392 643409 643461 643462 643472 643489 506 455 454 494 438 420 2767 351 294 74 0 10 37 766 458 369 13 259 91 16 1206 425 368 210 112 42 19 1176 387 294 204 209 125 2 1221 431 391 232 257 72 5 1388 398 261 23 3 12 11 708 422 342 268 35 39 12 1118 348 297 62 18 10 6 741 362 198 153 133 85 262 1193 Female Rats/Group vni: 250 mg/kg/day Animal Number Successive 10-Minute Intervals 1 2 3 4 5 643345 643347 643351 643358 643423 643441 643444 643457 643474 643481 416 324 320 390 348 278 251 185 48 7 339 290 312 363 341 380 361 120 5 68 320 189 245 162 209 356 244 112 10 7 331 77 342 268 40 413 276 276 148 5 382 284 63 5 0 428 318 248 238 18 6 Total 351 2149 1 770 225 1870 1 935 73 1198 3 732 0 1058 75 1193 4 738 2 1252 710 iol contain TSCA CBI INDIVIDUAL MOTOR ACTIVITY: DURATION OF MOVEMENTS (sec) Week 13 Male Rats/Group I: Omg/kg/day Animal Number 643162 643172 643195 643226 643237 643246 643253 643262 643303 643304 Successive 10-Minute Intervals 1 2 3 4 5 6 485 417 231 56 55 19 419 268 252 190 205 153 378 263 260 187 226 209 430 316 297 303 121 220 434 265 231 171 171 277 384 295 231 156 83 9 429 304 294 201 14 127 354 277 185 139 51 2 383 291 131 133 75 2 370 316 214 203 155 1 Total 1263 1487 1523 1687 1549 1158 1369 1008 1015 1259 Male Rats/Group HI: 25 mg/kg/day Animal Number 643173 643179 643180 643228 643240 643264 643272 643290 643292 643308 Successive 10-Minute Intervals 1 2 3 4 5 6 301 260 226 114 4 32 421 316 224 206 176 56 366 301 336 329 133 88 329 173 182 217 155 171 369 253 190 181 128 101 458 363 207 168 184 102 398 287 126 15 11 63 368 260 127 4 7 4 430 361 326 165 10 54 478 397 237 322 183 47 Total 937 1399 1553 1227 1222 1482 900 770 1346 1664 711 INDIVIDUALMOTO RACTIVITY: DLJRATION <OF MOVEN1ENTS (sec) Week 13 Male Rats/Group V: 100Dag/kg/day Animal Number Successive 10-Minute Intervals 1 2 3 4 5 . 6 Total 643175 a 643224 643243 643247 643250 643257 643275 643311 643314 643318 384 303 252 234 147 98 1418 351 218 270 249 183 186 1457 361 229 41 9 0 25 665 340 260 207 212 182 186 1387 341 269 215 154 201 0 1180 405 368 313 321 337 178 1922 306 189 129 115 125 91 955 395 274 317 57 242 187 1472 431 345 353 267 123 265 1784 Male Rats/Group vn: 250 mg/kg/day Animal Number Successive 10-Minute Intervals 1 2 3 4 5 643151 643165 643220 643225 643234 643236 643258 643266 643296 643316 285 147 45 24 4 388 340 340 221 138 440 289 249 228 155 296 223 250 183 213 299 71 6 3 64 395 298 230 135 138 304 300 156 150 92 357 236 177 115 120 438 399 369 305 240 482 345 279 105 288 6 Total 3 508 132 1559 29 1390 66 1231 13 456 28 1224 212 1214 16 1021 160 1911 269 1768 Sacrificed in extremis prior to evaluation. 712 ^wttfteuy Sanfflxod. Does not contain TSCA CB1 INDIVIDUAL MOTO]R. ACTivrrf: DLJRATION <DF MOVEN1ENTS (isec) Week 13 Female Rats/Group n: om g/kg/day Animal Number Succiessive 10-Minute Intervals 1 2 3 4 5 6 Total 643330 643336 643377 643387 643405 643415 643425 643426 643448 643453 433 296 197 189 77 50 1242 402 270 321 167 191 269 1620 315 204 242 127 66 284 1238 321 215 277 217 190 152 1372 402 265 220 205 141 12 1245 399 332 255 283 160 152 1581 453 370 359 148 2 0 1332 278 192 122 21 23 3 639 378 206 63 4 123 0 774 340 280 172 115 103 242 1252 Female Rats/Group IV: 25 mg/kg/day Animal Number Successive 10-Minute Intervals 1 2 3 4 5 643321 a 643324 643364 643380 643389 643390 643396 643410 643433 643458 499 346 306 315 361 427 407 247 252 18 396 231 202 196 102 428 376 306 148 22 382 278 246 87 154 520 429 226 20 64 420 372 304 249 138 336 133 29 199 11 476 335 282 29 37 6 Total 258 2085 114 1465 102 1229 111 1391 154 1301 136 1395 222 1705 8 716 270 1429 " Sacrificed in extremis prior to evaluation. 713 INDIVIDUAL MOTORACTIVTTY: DLIRATION (DF MOVENIENTS (;see) Week 13 Female Rats/Group VI: 1i00mg/kg/<day Animal Number 81nccessive 10-Minute Intervals 1 2 3 4 5 6 Total 643322 643323 643366 643367 643392 643409 643461 643462 643472 643489 521 376 401 380 66 5 1749 312 184 17 1 0 115 629 412 350 309 245 245 256 1817 456 347 241 215 297 42 1598 288 176 106 47 79 32 728 448 300 231 270 18 161 1428 386 265 330 177 17 181 1356 393 328 226 32 245 115 1339 294 157 130 71 158 121 931 350 178 27 1 211 82 849 Female Rats/Group vm: 250 mg/kg/day Animal Number Successive 10-Minute Intervals 1 2 3 4 5 643345 643347 643351 643358 643423 643441 643444 643457 643474 643481 426 227 15 168 232 244 177 118 130 111 392 347 248 83 81 350 263 129 185 81 367 223 133 87 15 308 246 97 114 145 471 407 267 117 45 445 249 298 296 153 387 261 28 4 38 321 277 148 207 212 6 Total 255 1323 26 806 237 1388 9 1017 14 839 2 912 96 1403 63 1504 149 867 54 1219 714 A Does not contain TSCA GtSf INDIVBDUALMOTORACTivrr Y: DIJRATION iOF MOVEMENTS (!sec) Recovery Male Rats/Group I: Omg/1eg/day Animal Number Succcssive 10-Minute Intervals 1 2 3 4 5 6 Total 643162 643172 643195 643226 643237 643246 643253 643262 643303 643304 279 187 123 77 85 82 833 423 233 154 111 170 173 1264 311 174 130 131 92 101 939 296 154 52 138 91 137 868 236 187 109 107 92 64 795 332 278 160 111 154 98 1133 329 157 164 197 147 215 1209 384 249 194 222 126 215 1390 268 158 118 129 58 108 839 382 246 199 222 192 205 1446 Male Rats/Group VH: 250 mg/kg/day Animal Number Successive 10-Minute Intervals 1 2 3 4 5 643151 643165 643220 643225 643234 643236 643258 643266 643296 643316 278 193 174 150 117 321 220 137 210 174 310 201 213 114 135 232 192 202 193 139 197 168 99 53 67 302 177 133 82 207 388 272 137 169 99 289 153 59 130 44 328 142 188 127 109 304 126 132 85 113 6 Total 111 1023 192 1254 168 1141 110 1068 3 587 54 955 193 1258 70 745 137 1031 125 885 715 companySanitized. Does not contain TSCA CBI INDIVIDUAL MOTOR ACTIVITY: DURATION OF MOVEMENTS (sec) Recovery Female Rats/Group n: 0 mg/kg/day Animal Number 643330 643336 a 643377 643387 643405 643415 643425 643426 643448 643453 Successive 10-Minute Intervals 1 2 3 4 5 6 307 160 146 132 74 201 381 246 201 168 169 128 315 185 191 109 79 155 208 137 167 65 110 17 384 316 221 262 79 1 322 262 127 71 117 90 330 228 160 198 76 139 333 204 177 171 72 110 387 267 166 234 174 90 Total 1020 1293 1034 704 1263 989 1131 1067 1318 Female Rats/Group Vffl: 250 mg/kg/day Animal Number 643345 643347 643351 643358 643423 643441 643444 643456 643474 643481 Successive 10-Minute Intervals 1 2 3 4 5 6 269 25 39 0 0 97 294 146 194 95 50 33 328 220 132 55 31 192 267 166 38 120 60 22 379 254 233 254 49 187 254 110 27 69 17 112 345 216 38 76 73 15 185 56 29 0 1 77 325 185 211 61 18 114 327 152 112 127 113 75 Total 430 812 958 673 1356 589 763 348 914 906 ' Sacrificed in extremis prior to evaluation. 716 APPENDIX J INDIVIDUAL MOTOR ACTIVITY ASSESSMENT: NUMBER OF MOVEMENTS 717 INDIVIDUAL MOTOR ACTIVITY: NUMBER OF MOVEMENTS Baseline Male Rats/Group I: Omg/kg/day Animal Number 643162 643172 643195 643226 643237 643246 643253 643262 643303 643304 Successive 10-Minute Intervals 123456 57 68 81 23 3 4 124 130 141 16 13 2 124 113 143 124 42 4 88 93 100 109 79 10 96 103 119 115 133 51 128 135 112 120 111 37 133 130 142 134 51 76 161 136 140 68 4 4 146 121 144 98 32 13 144 117 116 72 21 0 Total 236 426 550 479 617 643 666 513 554 470 Male Rats/Group in: 25 mg/kg/day Animal Number 643173 643179 643180 643228 643240 643264 643272 643290 643292 643308 Successive 10-Minute Intervals 1 2 3 4 5 6 128 143 75 14 0 9 122 134 147 37 3 0 110 128 105 8 5 13 6 0 146 120 137 31 141 127 121 23 3 5 66 62 65 56 10 4 136 135 52 14 2 6 119 147 118 99 18 6 91 102 140 106 8 11 109 114 112 116 32 3 Total 369 443 369 440 420 263 345 507 458 486 718 INDIVIDUAL MOTOR ACTIVITY: NUMBER OF MOVEMENTS Baseline Male Rats/Group V: lOOmg/kg/day Animal Number 643175 643224 643243 643247 643250 643257 643275 643311 643314 643318 Successive 10-Minute Intervals 1 2 3 4 5 6 93 97 142 81 6 11 107 121 134 114 137 116 135 145 146 95 28 5 121 130 115 22 1 2 127 109 118 62 4 13 145 151 57 9 28 1 111 117 58 8 26 78 141 154 140 90 38 26 112 151 89 30 19 14 140 154 112 39 12 19 Total 430 729 554 391 433 391 398 589 415 476 Male Rats/Group VD: 250 mg/kg/day Animal Number 643151 643165 643220 643225 643234 643236 643258 643266 643296 643316 Successive 10-Minute Intervals 1 2 3 4 5 6 156 181 134 54 1 0 130 139 171 167 155 90 124 121 54 4 1 0 141 141 130 65 78 15 152 137 132 110 48 64 144 137 124 7 21 145 142 124 93 23 3 6 143 138 145 95 4 5 122 155 12 9 11 9 125 130 25 7 1 8 Total 526 852 304 570 643 578 391 530 318 296 719 INDIVIDUAL MOTOR ACTIVITY: NUMBER OF MOVEMENTS Baseline Female Rats/Group n: 0 mg/kg/day Animal Number Succiessive 10-Minute Intervals 1 2 3 4 5 6 Total 643330 643336 643377 643387 643405 643415 643425 643426 643448 643453 121 124 130 28 2 4 409 136 147 125 127 5 7 547 121 145 15 143 100 11 535 153 131 108 132 135 28 687 142 125 128 126 139 37 697 145 159 47 14 142 40 547 105 109 79 115 94 10 512 151 151 140 100 136 125 803 125 125 142 125 20 4 541 137 150 24 37 155 15 518 male Rats/Group IV: 25 mg/kg/day Animal Number Successive 10-Minute Intervals 1 2 3 4 5 643321 643324 643364 643380 643389 643390 643396 643410 643433 643458 161 138 159 148 19 141 167 156 174 168 106 124 100 32 2 120 106 130 38 106 129 149 129 158 128 136 114 138 161 99 122 148 149 72 9 146 151 122 88 11 120 149 152 126 92 121 122 117 4 8 6 Total 7 632 104 910 8 372 72 572 28 721 3 651 31 531 2 520 12 651 12 384 720 INDIVIDUAL MOTOR ACTIVITY: NUMBER OF MOVEMENTS Baseline Female Rats/Group VI: lOOmg/kg/day Animal Number Successsive 10-Minute Intervals 1 2 3 4 5 6 Total 643322 643323 643366 643367 643392 643409 643461 643462 643472 643489 72 67 73 75 69 78 434 136 125 71 1 15 23 371 109 155 13 95 55 14 441 80 124 122 82 34 16 458 149 162 127 147 115 3 703 118 137 107 131 50 9 552 132 124 17 7 8 13 301 139 131 113 31 25 18 457 155 127 50 19 15 12 378 142 114 103 75 63 150 647 male Rats/Group vm: 250 mg/kg/day Animal Number Successive 10-Minute Intervals 1 2 3 4 5 643345 643347 643351 643358 643423 643441 643444 643457 643474 643481 136 161 152 146 166 129 134 157 51 9 147 154 172 138 126 155 139 94 6 54 140 143 129 143 146 152 163 107 11 16 125 46 131 149 35 132 105 133 124 11 121 135 58 6 0 118 144 134 129 25 6 Total 164 925 3 483 146 883 4 452 77 778 5 454 1 487 59 564 7 327 4 554 721 >oyS,iH, D...^^,,, ^^ INDIVIDUAL MOTOR ACTIVITY: NUMBER OF MOVEMENTS Week 13 Male Rats/Group I: 0 mg/kg/day Animal Number 643162 643172 643195 643226 643237 643246 643253 643262 643303 643304 SUQsessive 10-Mmute Intervals 1 2 3 4 5 6 Total 58 66 42 14 9 3 192 134 125 139 113 115 95 721 150 127 106 99 125 138 745 121 113 104 131 56 95 620 107 112 102 77 84 119 601 124 119 109 84 53 11 500 122 139 138 107 21 70 597 154 166 135 106 48 7 616 172 154 94 103 77 8 608 142 133 121 114 97 2 609 ale Rats/Group ffl: 25 mg/kg/day Animal Number 643173 643179 643180 643228 643240 643264 643272 643290 643292 643308 Successive lO-Minute Intervals 1 2 3 4 5 127 126 126 60 8 118 81 109 82 101 128 110 99 105 66 160 90 103 95 100 141 127 121 96 65 98 112 89 88 81 143 132 72 6 9 148 126 101 .5 8 129 115 142 98 15 97 126 94 84 64 6 Total 32 479 24 515 51 559 88 636 83 633 48 516 51 413 4 392 32 531 24 489 722 .QMpany ^aymSizeci. Dees not eaniiaira TCGA 6@ii INDIVIDUAL MOTOR ACTIVITY: NUMBER OF MOVEMENTS Week 13 Male Rats/Group V: lOOmg/kg/day Animal Number Sue;cessive 1C(-Minute Iintervals 1 2 3 4 5 6 Total 643175 a 643224 643243 643247 643250 643257 643275 643311 643314 643318 133 144 133 101 113 63 687 161 142 162 164 142 151 922 139 130 34 2 2 16 323 158 121 119 112 109 123 742 204 174 132 87 154 1 752 123 115 108 121 120 85 672 167 127 97 110 111 75 687 137 123 135 33 126 99 653 138 147 153 136 91 140 805 Male Rats/Group VH: 250 mg/kg/day Animal Number Sueicessive 1C-Minute I ntervals 1 2 3 4 5 643151 643165 643220 643225 643234 643236 643258 643266 643296 643316 162 97 47 28 6 120 127 129 95 73 139 139 124 121 102 144 118 138 114 132 132 60 6 5 54 155 144 129 92 93 143 150 103 123 74 131 141 102 65 69 110 111 101 101 106 109 128 96 59 146 6 Total 6 346 78 622 39 664 56 702 14 271 31 644 122 715 9 517 86 615 114 652 ' Sacrificed in extremis prior to evaluation. 723 companySanitized. Does not contain TSCA CBf INDIVIDUAL MOTOR ACTIVITY: NUMBER OF MOVEMENTS Week 13 Female Rats/Group n: 0 mg/kg/day Animal Number Suecessive 1C1-Minute Latervals 1 2 3 4 5 6 Total 643330 643336 643377 643387 643405 643415 643425 643426 643448 643453 139 124 69 84 52 36 504 131 127 137 81 88 135 699 150 113 131 80 87 140 701 161 147 146 142 113 123 832 147 114 128 112 95 11 607 157 158 159 154 135 142 905 117 115 133 97 5 5 472 166 130 117 25 31 6 475 122 141 66 8 73 1 411 141 149 111 93 31 145 670 Female Rats/Group IV: 25 mg/kg/day Animal Number Sue;cessive 1C1-Minute Latervals 1 2 3 4 5 643321 a 643324 643364 643380 643389 643390 643396 643410 643433 643458 125 134 129 146 134 122 130 109 119 14 135 114 98 109 87 152 162 154 107 26 153 127 153 65 121 49 67 31 4 8 123 128 151 137 105 139 92 18 123 12 113 133 115 26 26 6 Total 127 795 57 551 58 601 81 682 120 739 24 183 123 767 8 392 128 541 ' Sacrificed in extremis prior to evaluation. 724 INDIVIDUAL MOTOR ACTIVITY: NUMBER OF MOVEMENTS Week 13 Female Rats/Group VI: 100 mg/kg/day Animal Number Succes>sive 10-Minute Intervals 1 2 3 4 5 6 Total 643322 643323 643366 643367 643392 643409 643461 643462 643472 643489 65 56 51 53 13 1 239 161 110 24 1 2 82 380 132 123 141 137 127 141 801 103 130 129 108 118 34 622 153 129 86 56 83 37 544 112 128 106 105 20 104 575 146 145 128 128 13 118 678 142 144 125 23 123 52 609 163 107 87 56 121 97 631 139 108 33 3 147 65 495 male Rats/Group Vffl: 250 mg/kg/day Animal Number Successive 10-Minute Intervals i 2 3 4 5 643345 643347 643351 643358 643423 643441 643444 643457 643474 643481 116 112 14 101 127 121 123 77 83 76 138 136 135 75 79 152 132 110 122 53 156 127 96 93 19 163 136 100 95 90 101 122 134 54 24 89 101 112 133 83 134 123 25 8 21 143 138 110 152 127 6 Total 101 571 23 503 135 698 18 587 25 516 7 591 58 493 43 561 96 407 48 718 725 Company Sanitized. Does not contain TSCA CBI INDIVIDUAL MOTOR ACTIVITY: NUMBER OF MOVEMENTS Recovery Male Rats/Group I: 0 mg/kg/day Animal Number 643162 643172 643195 643226 643237 643246 643253 643262 643303 643304 Succiessive 10-Mmute Intervals 1 2 3 4 5 6 Total 134 139 105 64 61 65 568 88 70 57 52 67 56 390 122 91 72 79 60 77 501 130 79 21 81 54 86 451 153 132 78 78 71 48 560 146 136 99 71 102 70 624 140 90 96 117 88 115 646 152 128 101 99 89 100 669 142 90 82 77 66 67 524 121 109 89 87 113 115 634 lie Rats/Group VH: 250 mg/kg/day Animal Number Successive lO-Minute Intervals 1 2 3 4 5 643151 643165 643220 643225 643234 643236 643258 643266 643296 643316 144 131 123 100 77 136 109 86 136 102 150 112 105 82 96 131 104 98 126 95 96 66 56 42 44 116 95 92 63 100 122 102 63 76 50 164 87 35 67 33 128 85 81 74 66 124 68 75 36 61 6 Total 87 662 118 687 115 660 88 642 7 311 39 505 90 503 49 435 93 527 72 436 726 Company Sanitized. Does not contain TSCA CBl INDIVIDUALM[OTORACTIV][TY: NUMBED1 OF MOVEMENTS5 Recovery Female Rats/Group n: o mg/kg/day Animal Number 643330 643336 a 643377 643387 643405 643415 643425 643426 643448 643453 Succesisive 10-Minute Intervals i 2 3 4 5 6 Total 134 123 101 100 58 155 671 ... ... 126 132 ... ... ... * 98 114 116 102 688 152 118 132 101 70 126 699 126 106 113 69 102 14 530 135 152 129 155 66 5 642 139 132 108 76 92 84 631 157 130 84 129 62 104 666 145 151 127 126 64 104 717 130 129 105 119 87 55 625 Female Rats/Group vm: 250 mg/kg/day Animal Number Successive 10-Minute Intervals 1 2 3 4 5 643345 643347 643351 643358 643423 643441 643444 643456 643474 643481 153 18 30 0 0 137 103 112 78 47 154 138 99 43 42 142 126 56 101 52 117 118 117 122 42 142 85 38 50 22 149 144 55 62 89 125 45 29 1 3 149 125 126 66 28 136 109 82 93 85 6 Total 69 270 43 520 129 605 32 509 121 637 84 421 34 533 49 252 97 591 87 592 ' Sacrificed in extremis prior to evaluation. 727 CompanySanitized. Does not contain TSCA CSt APPENDIX K INDIVIDUAL CLINICAL PATHOLOGY DATA 728 Company Sanitized. Does not contain TSCA CBl INDIVIDUAL ANIMAL CLINICAL PATHOLOGY DATA EXPLANATORY NOTES ABBREVIATIONS: General: ADEQ CLOT DECR MSR NT NT-HEMOL OK QNS RNV UTD adequate sample clotted decreased no sample received for testing not taken or not performed not taken due to hemolysis greater than or equal to moderate sample condition OK for testing quantity not sufficient result not valid unable to determine greater than less than Individual COND RBC HGB HCT MCV MCH MCHC RDW ARET WBC AMEU ANPR ALYM AMON AEOS ABAS ALUC ABLT AMSC PLT SPEC AL HSN Hematology Values: - sample condition - red blood cell count - hemoglobin - hematocrit - mean corpuscular volume - mean corpuscular hemoglobin - mean corpuscular hemoglobin concentration - red cell distribution width - absolute reticulocyte count - white blood cell count - absolute neutrophil (all forms) - absolute neutrophil precursor - absolute lymphocyte - absolute monocyte - absolute eosinophil - absolute basophil - absolute large unstained cell - absolute blast leukocyte - absolute miscellaneous leukocyte - platelet count - special observations - atypical lymphocyte - hypersegmented neutrophil 729 .Company Sanitized. Does not contain TSCA CSi INDIVIDUAL ANIMAL CLINICAL PATHOLOGY DATA EXPLANATORY NOTES (Continued) ABBREVIATIONS: (Continued) Individual NORM ANIS MIC MAC POLY HYPO ECHI ACAM TARG RX HJB SPEC Red Blood Cell Morphology Values: - normal - anisocytosis - microcytes - macrocytes - polychromasia - hypocbromasia - echinocytes - acanthocytes - target cells - rouleaux - Howell-Jolly body - special observations not observed or not examined; see whole blood sample condition Individual NORM SM DB PC GP BP TOX VC SPEC White Blood Cell /. Platelet Morphology Values: - normal - smudge white blood cells - Dohle bodies if - platelet clumps (graded as 1 - giant platelets - bizarre platelets - toxic neutrophils present at any level) - vacuolated cytoplasm - special observations not observed or not examined; see whole blood sample condition Individual PHEM FLIP PICT PT APTT Coagulation Values: - plasma hemolysis - plasma lipemia - plasma icterus - prothrombin time - activated partial thromboplastin time 730 Campany Sanitized. Does not contain TSCA C6( INDIVIDUAL ANIMAL CLINICAL PATHOLOGY DATA EXPLANATORY NOTES (Continued) ABBREVIATIONS: (Continued) Individual SHEM SLIP SICT AST ALT SDH ALKP BILI BUN CREA CHOL TRIG GLUC TP ALB GLOB CALC IPHS NA K CL PHEM FLIP PICT PFLU SPEC Serum and Plasma Chemistry Values: - serum hemolysis - serum lipemia - serum icterus - aspartate aminotransferase - alanine aminotransferase - sorbitol dehydrogenase - alkaline phosphatase - total bilirubin - urea nitrogen - creatinine - cholesterol - triglycerides - glucose - total protein - albumin - globulin - calcium - inorganic phosphorous - sodium - potassium - chloride - plasma hemolysis from blood sample for fluoride determination - plasma lipemia from blood sample for fluoride determination - plasma icterus from blood sample for fluoride determination - plasma fluoride - special observations Individual Urinalysis Values: QUAL COL - CLAR VOL - quality color clarity volume (modifies color) UOSM SG pH - UGLU - urine osmolality specific gravity the logarithm of the reciprocal of the hydrogen ion concentration urine glucose KET - ketone UBIL - BLD - urine bilirubin blood URO UFLU UMTP SPEC - urobilinogen urine fluoride urine protein special observations Individual EPIT UWBC URBC NCRY MICR SPER SPEC Urine Microscopic Examination - epithelial cells - urine white blood cells - urine red blood ceils - normal crystals - microorganisms - sperm - special observations Values: 731 1. Doe not contain TSCA CSI  INDIVIDUAL ANIMAL CLINICAL PATHOLOGY DATA EXPLANATORY NOTES (Continued) KEY: Red Blood Cell Morphology Values, White Blood Cell / Platelet Morphology Values (with the exception of Platelet Clumps), and Special Observations: 1 - trace 2 - few 3 - moderate 4 - many Urine Microscopic Values: EPIT NCRY/MICR per high power field (40x)_____per high power field (40x)_____per few - 1-10 few - l-25t/field moderate - 11-50 moderate - 26-50%/field many - >50 many - >50^/field SPERM/MUCUS low power field l - 1-5 2 - 6-20 3 - >20 (IQx) NOTES: When individual animal data are not reported, it may be due to one of the following reasons or other reasons, all of which are explained in the study records: the sample was clotted (for hematology or coagulation there was insufficient sample for analysis (QNS) a valid result could not be obtained (RNV) the sample was not suitable for evaluation the animal died prior to sample collection no sample was available for analysis (NSR) data) (CLOT) When an individual observation was recorded as being less than a certain value, calculations were performed on half the recorded value. For example, if bilirubin was reported as <0.1, 0.05 was used for any calculations performed with that bilirubin data. 732 6sanpMg(Sanitb8d. Does not contain TSCA CBt B H-24516: Subchronic Toxicity 90-Day Gavage Study in Rats with One-Generation Reproductive Evaluations Animal Number COND RBC xlO^ /UL 3B g/'dL Male, Group: 643143 643150 643185 643189 643204 643205 643235 643241 643288 643300 1-0 mg;'kg - OK OK OK OK OK OK OK OK OK OK D ay 44 7 .72 7 .77 8 .21 8 .64 8 .18 7 .79 8 .04 8 .37 8 .51 8 .96 Male, Group: III - 25 mg/kg - Day 44 643173 643179 643180 643228 643240 643264 643272 643290 643292 643308 OK 8 .38 OK 8 .48 OK 7 .97 OK 8 .09 OK 8 .38 OK 8 .16 OK 8 .67 OK 8 .62 OK 8 .42 OK 8 .18 14 .4 15 .1 14 .7 15 .2 15 .1 14 .9 14 .9 15 .8 15 .1 16 .0 15 .7 15 .6 14 .6 15 .0 15 .5 15 .2 15 .6 15 .7 14 .8 15 .6 IndiviLdual Hemato logy Value;s HICT MiCV fL MiCH P9 MC:HC g/'dL 44 .3 44 .9 45 .2 46 .4 46 .4 45 .9 43 .7 48 .0 45 .8 49 .6 49 .0 46 .9 44 .2 46 .3 46 .3 44 .2 47 .2 47 .9 46 .1 47 .4 57 .3 57 .7 55 .0 53 .7 56 .7 58 .9 54 .4 57.4 53 .8 55.4 58 .5 55 .4 55 .5 57 .2 55 .2 54 .2 54 .5 55 .6 54 .8 57 .9 18 .7 19.4 18 .0 17 .6 18 .5 19 .1 18 .5 18 .8 17 .7 17 .9 18 .7 18 .4 18 .3 18 .6 18 .5 18 .6 18 .0 18 .2 17 .6 19 .0 32 .6 33 .7 32 .7 32 .8 32 .6 32 .4 34 .0 32 .9 32 .9 32 .3 32 .0 33 .2 33 .0 32 .5 33.4 34 .3 33 .1 32 .8 32 .1 32 .9 R DW ARET 3clO^/uL 12 .4 11 .8 12 .0 12 .2 12 .1 13 .2 11 .9 12 .3 11 .5 12 .3 11 .9 11 .6 12 .4 12 .0 11 .2 12 .6 11 .7 11 .7 12 .7 12 .7 195. 161. 199. 205. 177. 299. 199. 157. 189. 215. 198. 188. 201. 177. 146. 216. 141. 163. 176. 248. 733 Company Sanitized. Does not con ^ ^^ H-24516: Subchronic Toxicity i^^i 90-Day Gavage Study in Rats with One-Generation Reproductive Evaluations Animal Number COND RBC xl0^6/uL HGB g/dL Male, Group: V - 100 mg/kg - Day 44 643175 643224 643243 643247 643250 643257 643275 643311 643314 643318 OK 8.02 15.1 OK 8.24 14.7 OK 8.05 15.2 OK 7.76 14.7 OK 8.09 15.6 OK 7.76 15.0 OK 8.65 16.1 OK 7.33 14.2 OK 7.69 14.4 OK 8.01 15.6 Male, Group: VII - 250 mg/kg - Day 44 643174 643193 643194 643201 643215 643252 643259 6432-60 643298 643315 OK OK OK OK OK OK - OK OK OK OK 8.40 8.13 7.85 8.31 8.30 8.03 7.59 8.27 7.46 8.26 14.9 14.9 14.7 14.9 14.6 14.6 14.7 15.1 13.9 15.3 Indiv idual Hemat ology Valu<3S HCT % MCV fL MCH P9 MCHC g/dL 46.1 45.2 47.1 43.3 47.7 45.7 49.1 42.4 44.4 47.2 45.9 44.6 44.8 46.3 45.4 44.7 43.9 45.7 42.7 48.0 57.5 54.8 58.5 55.8 58.9 59.0 56.8 57.8 57.7 58.9 54 .6 54.9 57.1 55.7 54 .6 55.7 57.8 55.2 57.2 58.1 18.9 17.9 18.9 19.0 19.3 19.3 18.7 19.4 18.8 19.5 17.7 18.3 18.7 18.0 17.6 18.2 19.4 18.2 18.6 18.6 32.8 32.6 32.3 34.0 32.8 32.7 32.9 33.5 32.5 33.1 32.4 33.3 32.8 32.3 32.1 32.7 33.5 33.0 32.5 31.9 RDW AR t xlO*3/ 10.8 18 11.7 15 11.7 20 11.4 14 12.1 16 11.5 18 12.5 20 12.6 1 12.5 18 12.1 1 13.0 2 12.4 1 13.3 1 12.3 1 12.7 12 12.4 20 12.9 18 11.8 1 12.7 16 12.6 1 734 a H-24516: Subchronic Toxicity 90-Day Gavage Study in Rats with One-Generation Reproductive Evaluations Animal Number ANPR xlO^/uL ALYM xlO^/uL AMON xl0''3/UL Ind ividual Hematology Values AEOS xlO^/uL ABAS xlO^/uL ALUC xl0^3/uL ABLT xlO^/uL AMSC XIO^/UL PLT xl0^3/uL Male, Group: 1-0 mg/kg - Day 44 643143 NT 12.33 0.34 0.20 0.10 0.28 NT NT 1070 643150 NT 14.86 0.36 0.11 0.17 0.22 NT NT 1229 643185 NT 15.11 0.21 0.19 0.08 0.29 NT NT 1028 643189 NT 16.05 0.57 0.20 0.08 0.17 NT NT RNV 643204 NT 15.87 0.30 0.14 0.12 0.25 NT NT 1242 643205 NT 15.84 0.23 0.11 0.16 0.33 NT NT 1190 643235 NT 13.44 0.30 0.12 0.10 0.24 NT NT 1179 643241 NT 10.41 0.30 0.19 0.08 0.14 NT NT 947 643288 NT 12.56 0.44 0.11 0.11 0.22 NT NT 1232 643300 NT 15.47 0.31 0.19 0.09 0.29 NT NT 1149 Male, Group: III - 25 mg/kg - Day 44 643173 NT 7.30 0.33 0.22 0.03 0.11 NT NT 940 643179 NT 11.53 0.43 0.19 0.09 0.15 NT NT 1171 643180 NT 7.94 0.45 0.31 0.07 0.16 NT NT 992 643228 NT 14.39 0.62 0.16 0.09 0.75 NT NT 1161 643240 NT 12.52 0.32 0.19 0.08 0.20 NT NT 1133 643264 HT" 20.17 0.37 0.19 0.11 0.26 NT NT 1102 643272 NT 18.39 0.41 0.22 0.17 0.38 NT NT 1119 643290 NT 13.66 0.50 0.23 0.11 0.35 NT NT 1128 643292 NT 10.65 0.30 0.26 0.11 0.18 NT NT 943 643308 NT 13.74 0.31 0.30 0.13 0.18 NT NT RNV 735 Company Sanitized. Does not con H-24516: Subchronic Toxicity 90-Day Gavage Study in Rats with One-Generation Reproductive Evaluations Animal Number ANPR ;KlO^/uL Mi YM xl0*3/ UL A1MON X10''3 /UL Individual Hemat;ology' Valuel3 A:EOS X ;10*3 /UL ABAS >Cl0"3/ uL A;LUC .xl0*3 /UL ABLT x HO^/uL AMSC x]LO"3/uL PLT X].0^3/uL Male, Group: V - 100 mei/kg - Day 44 643175 NT 13. 19 0 .64 0 .18 0. 10 0 .19 NT NT 1384 643224 NT 11. 42 0 .00 0 .14 0. 00 0 .00 NT NT 1012 643243 NT 17. 83 0 .41 0.10 0. 14 0 .21 NT NT RNV 643247 NT 11. 20 0 .46 0 .15 0. 00 0 .00 NT NT RNV 643250 MT 20. 07 0 .28 0 .25 0. 20 0 .25 NT MT 762 643257 NT 11. 57 0 .50 0 .11 0. 12 0 .22 NT NT 977 643275 MT 14. 14 0 .40 0 .13 0. 06 0 .21 NT NT 920 643311 MT 20. 97 0 .53 0 .11 0. 19 0 .27 NT NT 1271 643314 MT 10. 57 0 .29 0 .17 0. 14 0 .18 NT NT 1315 643318 MT 15. 57 0 .42 0 .11 0. 11 0 .23 NT NT 913 Male, Group: VII - 250 ni9/kg - Day 44 643174 NT 15. 84 0 .74 0 .23 0. 10 0 .17 NT NT RNV 643193 MT 16. 61 0 .44 0 .00 0. 00 0 .00 NT NT 963 - 643194 "MT 21. 54 0 .45 0 .13 0. 15 0 .41 NT NT 1032 643201 MT 17. 41 0 .34 0 .21 0. 12 0 .27 NT NT 1163 643215 MT 12. 45 0 .32 0 .18 0. 06 0 .24 NT NT 861 643252 NT 17. 25 0 .42 0 .18 0. 11 0 .26 NT NT RNV 643259 NT 15. 15 0 .61 0 .15 0. 13 0 .52 NT NT 1122 643260 MT 14. 00 0 .39 0 .13 0. 07 0 .23 NT NT 1049 643298 MT 14. 07 0 .34 0 .16 0. 16 0 .17 NT NT 941 643315 MT 14. 31 0 .39 0 .08 0. 08 0 .30 NT NT 936 736 CompanySanitized. Does not cont H-24516: Subchronic Toxicity 90-Day Gavage Study in Rats with One-Generation Reproductive Evaluations Animal Number COND RBC xl0^ 6/uL HGB 9/dL Male, Group: 643143 643150 643185 643189 643204 643205 643235 643241 643288 643300 1-0 mg/kg - OK OK CLOT OK OK OK OK OK OK OK Day 91 8.26 8.55 NT 9.10 8.76 7.86 9.16 9.49 9.30 9.43 Male, Group: 643173 643179 643180 643228 643240 643264 643272 643290 643292 643308 III - 25 ing/kg - Day 91 OK OK OK OK OK OK" CLOT OK OK OK 9.22 8.47 8.59 7.81 8.70 8.29 NT 8.80 8.62 8.64 14.5 15.3 NT 14.9 15.5 14.3 15.5 16.6 15.5 15.8 16.8 14.8 14.9 14.0 15.4 14.7 NT 15.2 14.7 15.8 Indiv idual Hemat ology Value S HCT % MCV L MCH pg MCHC g/dL 46.9 48.4 NT 46.7 50.1 45.4 49.4 54.6 49.8 49.0 53.6 45.6 46.0 43.3 47.7 46.3 NT 47.8 46.7 49.9 56.8 56.6 NT 51.4 57.2 57.9 54.0 57.5 53.5 52.0 58.1 53.8 53.6 55.4 54.8 55.8 NT 54.3 54.2 57.8 17.5 17.9 NT 16.4 17.6 18.3 16.9 17.5 16.7 16.7 18.2 17.4 17.3 17.9 17.6 17.8 NT 17.3 17.1 18.3 30.9 31.6 NT 31.9 30.9 31..6 31.3 30.4 31.2 32.2 31.3 32.4 32.4 32.3 32.2 31.8 NT 31.8 31.5 31.7 RDW ARET t xl0^3/uL 13.5 12.3 NT 13.7 13.2 14.7 13.1 12.8 12.7 12.7 12.5 13.5 13.1 12.8 12.4 13.0 NT 13.0 12.9 12.8 188. 125. NT 186. 213. 274. 187. 183. 102. 168. 163. 162. 173. 175. 175. 227. NT 180. 153. 206. 737 Company Sanitized. Does not contai H-24516: Subchronic Toxicity 90-Day Gavage Study in Rats with One-Generation Reproductive Evaluations Animal Number COND RBC xlO^/uL HGB g/dL Male, Group: V - 100 mg/kg - Day 91 643175 643224 643243 643247 643250 643257 643275 643311 643314 643318 NSR NT NT OK 8.23 14.3 OK 8.33 15.2 OK 7.67 14.2 OK 8.15 15.1 OK 8.27 15.1 OK 9.03 15.9 OK 8.29 15.1 OK 8.29 14.8 OK 8.15 15.0 Male, Group: VII - 250 ing/kg - Day 91 643174 643193 643194 643201 643215 643252 643259 643260 643298 643315 OK 8.64 14.6 OK 7.67 14.0 OK 8.12 14.5 OK 8.04 13.8 OK 8.18 14.5 OK 7.82 14.1 OK 8.20 15.3 OK 8.41 15.2 OK 7.12 12.5 OK 7.70 14.0 IndivjLdual Hemato:Logy Value S HCT t MCV fL MCH P3 MCHC g/dL ' NT 45.1 47.4 44.1 46.1 47.5 51.3 48.8 46.7 47.4 45.6 44.0 46.2 43.7 46.6 45.9 49.1 48.4 40.2 44 .2 NT 54.8 56.9 57.5 56.5 57.4 56.8 58.8 56.3 . 58.2 NT 17.4 18.2 18.5 18.5 18.2 17.6 18.2 17.9 18.4 52.7 57.3 56.9 54.4 57.0 58.7 60.0 57.6 56.4 57.4 16.9 18.2 17.9 17.2 17.8 18.0 18.6 18.0 17.5 18.2 NT 31.7 32.0 32.2 32.8 31.7 31.0 30.9 31.8 31.5 32.1 31.9 31.5 31.6 31.2 30.7 31.1 31.3 31.1 31.8 RDW ARET t xl0^3/uL NT 13.4 13.1 12.8 13.5 13.3 13.0 14.0 14.2 13.8 15.0 15.9 15.0 14.1 15.1 17.8 15.9 12.9 14.2 14.9 NT 153. 220. 238. 159. 185. 147. 237. 203. 222. 237. 185. 229. 177. 187. 280. 296. 156. 194. 240. 738 Company Sanitized. Does not cont H-24516: Subchronic Toxicity 90-Day Gavage Study in Rats with One-Generation Reproductive Evaluations Animal Number A NPR i 10^3 /UL A LYM xl0"3 /UL A1MON X10 ^3 /UL Individual. Hematologir Value S A EOS } cl0^3 /UL A BAS 5cl0^3 /UL A LUC 3cl0^3 /UL A BLT 3010^3 /UL A MSC l 010^3 /UL PLT ?ClO^/uL Male, Group: I - 0 mg;fkg - D ay 91 643143 643150 643185 643189 643204 643205 643235 643241 643288 643300 0 .00 0 .00 NT NT NT 0 .00 NT NT 0 .00 0 .00 13 .10 10.43 NT 14 .20 12 .29 10 .40 12 .36 11 .03 11 .02 8 .99 Male, Group: 643173 643179 643180 643228 643240 643264 643272 643290 643292 643308 III - 25 mg/kg - Day 91 0 .00 NT NT 0 .00 NT 0 .00" NT NT NT 0 .00 7 .22 8 .43 6 .32 11 .17 9 .78 17 .10 NT 9 .19 8 .03 8 .90 0 .49 0 .75 NT 0 .69 0 .30 0 .13 0 .55 0 .37 0 .42 0 .33 0 .20 0 .35 0 .32 0 .77 0 .38 0 .19 NT 0 .30 0 .24 0 .69 0 .16 0 .13 NT 0 .21 0 .14 0 .00 0 .21 0 .18 0 .14 0 .22 0 .29 0 .10 0 .23 0 .46 0 .13 0 .00 NT 0 .09 0 .12 0 .35 0 .00 0 .00 NT 0 .07 0 .07 0 .00 0 .07 0 .09 0 .00 0 .00 0 .00 0 .05 0 .03 0 .00 0 .07 0 .00 NT 0 .05 0 .04 0 .00 0 .00 0 .00 NT 0 .10 0 .11 0 .00 0 .26 0 .12 0 .00 0 .00 0 .00 0 .11 0 .08 0 .00 0 .18 0 .00 NT 0 .15 0 .09 0 .00 0 .00 0 .00 NT NT NT 0 ,.00 NT NT 0 .00 0 .00 0 .00 NT NT 0 .00 NT 0 .00 NT NT NT 0 .00 0 .00 0 .00 NT NT NT 0 .00 NT NT 0 .00 0 .00 0 .00 NT NT 0 .00 NT 0 .00 NT NT NT 0 .00 1251 1145 NT 854 1330 1216 1225 RNV 1227 RNV 925 1160 952 1157 1186 1055 NT 1175 861 1025 739 Company Sanitized. Does no H-24516: Subchronic Toxicity 90-Day Gavage Study in Rats with One-Generation Reproductive Evaluations Animal Number ANPR : iclO^/uL A:LYM xlO^,/UL A]MON Xl 0'3 /UL Individua3. Hematology Value S A EOS ?Cl0^3 /uL A BAS s010^3 /uL AL,UC >clO^/ uL ABLT ? cl0^3/uL AMSC 3C10*3/UL PLT > C10"3/UL Male, Group; V - 100 roc3/kg - Day 91 643175 643224 643243 643247 643250 643257 643275 643311 643314 643318 NT NT NT NT NT 0.00 0.00 NT NT NT NT 9 .10 13 .09 8 .72 12 .20 12 .64 10 .01 18 .83 8 .43 11 .05 NT 0 .14 0 .51 0 .47 0 .18 0 .74 0 .56 0 .21 0.25 0 .27 Male, Group: VII - 250 ing/kg - Day 91 643174 643193 643194 643201 643215 643252 643259 643260 643298 643315 0.00 NT NT NT NT NT 0.00 0.00 0.00 NT 10 1C 11 .60 18 .36 14 .26 9 .36 12 .81 13 .40 8 .69 10 .28 11 .70 0n .4A 4A 0 .28 0 .49 0 .34 0 .34 0 .48 0 .79 0 .24 0 .39 0 .23 NT 0 .05 0 .08 0 .19 0 .32 0 .29 0 .11 0 .21 0 .20 0 .07 r0\ .4H 4 0 .23 0 .24 0 .21 0 .34 0 .15 0 .32 0 .00 0 .13 0 .08 NT 0 .04 0 .12 0 .05 0 .06 0 .00 0 .00 0 .00 0 .05 0 .05 0" .0~0* 0 .06 0 .10 0 .07 0 .08 0 .08 0 .00 0 .00 0 .00 0 .05 NT 0. 08 0. 27 0. 08 0. 53 0. 00 0. 00 0. 00 0. 14 0. 22 0. 00 0. 08 0. 34 0. 15 0. 26 0. 28 0. 00 0. 00 0. 00 0. 18 NT NT NT NT NT 0.00 0.00 0.00 MT NT 0.00 NT NT NT NT NT 0.00 0.00 0.00 NT NT NT NT NT NT 0.00 0.00 0.00 NT NT 0.00 NT NT NT NT NT 0.00 0.00 0.00 NT NT 1037 1272 1172 928 KNV 885 1228 1246 970 RNV 1015 RNV 1245 1047 1177 RNV 1131 1153 1008 740 .Company Sanitized. Does not H-24516: SubchronicToxicity 90-Day Gavage Study in Rats with One-Generation Reproductive Evaluations Animal Number COND RBC X10''6/uL HGB 9/dL Male, Group: 643162 643172 643195 643226 643237 643246 643253 643262 643303 643304 1-0 ing/kg - OK OK OK OK OK OK OK OK OK OK Day 125 9.18 8.85 8.99 8.87 8.57 9.63 8.42 8.57 9.39 8.84 15.4 14.8 15.4 16.0 15.3 16.2 15.3 15.5 16.2 15.9 Male, Group: VII - 250 nag/kg - Day 125 643151 643165 643220 643225 643234 643236 64325B 643266 643296 643316 OK 7.68 14.5 OK 8.01 14.8 OK 8.09 14.0 OK 8.01 14.4 OK 8.00 14.4 .OK- 7.49 13.5 OK 7.94 14.3 OK 7.71 13.1 OK 8.60 16.2 OK 8.17 13.9 Individual Hemat ology Value s HCT % MCV fL MCH pg MCHC 3/dL 47.8 46.3 46.4 49.9 47.5 51.0 47.6 47.0 51.0 48.9 44.2 44.4 43.3 44.4 44.3 41.1 44.4 39.7 50.1 42.7 52.0 52.3 51.7 56.3 55.4 52.9 56.6 54.9 54.3 55.3 57.6 55.4 53.5 55.3 55.4 54.9 56.0 51.5 58.2 52.2 16.8 16.7 17.1 18.0 17.8 16.8 18.2 18.1 17.2 17.9 18.9 18.4 17.3 17.9 18.0 18.1 18.0 17.0 18.8 17.0 32.3 31.9 33.1 32.0 32.2 31.8 32.2 32.9 31.7 32.4 32.8 33.2 32.3 32.4 32.6 33.0 32.1 32.9 32.3 32.6 RDW ARE xlO^/uL 14.5 224 15.2 216 13.3 167 12.6 188 13.4 171 12.9 190 14.0 231 13.4 142 14.1 205 12.8 147 11.5 132 12.4 174 12.9 180 13.4 153 10.8 132 14.9 176 12.3 124 14.3 153 11.7 119 13.1 159 741 Santtteed.Doe.notc Company 6 H-24516: Subchronic Toxicity 90-Day Gavage Study in Rats with One-Generation Reproductive Evaluations Animal Number / WPR xlO^1/uL A:LYM xl0^3 /UL A MON > cl0*3 /uL Indiv idual. Hemat olog>' Values3 A EOS l cl0*3 /uL A]BAS ; 010^3,/uL A:LUC l (10*3 /uL ABLT x 10^3/UL AMSC x3LO*3/uL PLT 1 clO'3/uL Male, Group: I - 0 rng/1eg - D.ay 125 643162 643172 643195 643226 643237 643246 643253 643262 643303 643304 NT 5 .90 NT 11 .52 NT 8 .71 NT 13 .24 NT 9 .50 NT 17 .83 MT 10 .32 NT 8 .47 NT 12 .48 NT 8 .06 0 .30 0 .38 0.20 0 .57 0 .11 0 .74 0 .15 0 .26 0 .41 0 .32 0 .17 0 .13 0 .08 0 .16 0 .06 0 .33 0 .10 0 .10 0 .15 0 .07 0 .13 0 .09 0 .05 0 .05 0 .04 0 .09 0 .09 0 .06 0 .07 0 .05 0 .11 0 .17 0 .09 0 .15 0 .11 0 .49 0 .15 0 .10 0 .23 0 .08 NT NT NT NT NT . .NT NT NT NT NT Male, Group: VII - 250 nig/kg - Day 125 643151 NT 11 .05 0 .18 0 .06 0 .08 0 .16 NT 643165 NT 8 .45 0 .26 0 -09 0 .05 0 .16 NT 643220 NT 9 .41 0 .24 0 .08 0 .09 0 .22 NT 643225 NT 15 .07 0 .27 0 .10 0 .12 0 .20 NT 643234 NT 13 .30 0 .45 0 .19 0 .19 0 .13 NT 643236 WT" 8 .50 0 .25 0 .08 0 .06 0 .19 NT 643258 NT 7 .47 0 .22 0 .06 0 .04 0 .08 NT 643266 NT 7 .22 0 .23 0 .11 0 .03 0 .17 NT 643296 NT 10 .59 0 .20 0 .09 0 .07 0 .15 NT 643316 NT 15 .13 0 .53 0 .48 0 .10 0 .30 NT NT 1185 NT 1154 NT 1075 NT RNV NT 1044 NT 872 NT 1172 NT 910 NT RNV NT RNV NT 1058 NT 1167 NT 1181 NT 1016 NT 1099 NT RNV NT 940 NT 1148 MT 1088 NT 1035 742 Company SanlteeADoe. not cont H-24516: Subchronic Toxicity 90-Day Gavage Study in Rats with One-Generation Reproductive Evaluations Animal Number COND RBC xlO^/uL HGB g/dL Female, Group: 643354 643361 643362 643374 643398 643406 643436 643463 643477 643486 11-0 OK OK OK OK OK OK OK OK OK OK ing/kg - Day 45 8.16 8.39 8.32 8.39 7.85 8.32 8.26 8.12 8.41 8.37 15.4 15.4 16.2 15.3 14.8 16.2 15.4 15.1 15.0 15.4 Female, Group: IV - 25 nig/kg - Day 45 643321 643324 643364 643380 643389 643390 643396 643410 643433 643458 NSR OK OK OK OK OKOK OK OK OK NT 7.34 7.89 7.65 7.81 8.35 8.24 7.70 7.86 7.85 NT 14.8 14.9 14.8 14.6 15.4 14.8 14.4 14.7 14.9 Indiv:idual Hemat ology Value B HCT MCV fL MCH pg MCHC g/dL 46.2 48.3 47.4 46.3 45.0 48.5 46.6 47.5 47.1 46.0 NT 44.6 44.9 44.0 43.9 49.0 46.2 43.7 44.4 43.3 56.6 57.5 57.0 55.2 57.4 58.3 56.4 58.5 56.0 55.0 NT 60.7 57.0 57.6 56.2 58.7 56.1 56.8 56.5 55.1 18.9 18.4 19.4 18.2 18.9 19.5 18.6 18.6 17.8 18.5 NT 20.1 18.8 19.3 18.7 18.5 18.0 18.7 18.7 19.0 33.4 32.0 34.1 33.0 33.0 33.4 33.0 31.9 31.8 33.6 NT 33.2 33.1 33.6 33.2 31.4 32.0 33.0 33.2 34.5 RDW ARET xlO"3/uL 11.7 12.2 11.2 12.0 11.1 12.2 11.3 11.5 12.4 11.6 NT 12.1 11.4 11.8 11.9 12.6 11.4 12.6 11.4 11.8 220. 222. 198. 217. 199. 226. 148. 208. 240. 203. NT 251. 173. 194. 225. 265. 196. 248. 168. 228. 743 Company s.^o...""""" H-24516: Subchronic Toxicity 90-Day Gavage Study in Rats with One-Generation Reproductive Evaluations Animal Number COND RBC xlO^ /uL Hi3B 9/'dL Female, Group: VI - K 10 mg/ki3 - Day 45 643322 643323 643366 643367 643392 643409 643461 643462 643472 643489 OK 7 .93 14 .9 OK 8 .68 15 .5 OK 7 .86 14 .9 OK 8 .38 15 .1 OK 9 .03 15 .9 OK 7 .88 15 .1 OK 7 .65 14 .9 OK 8 .37 15 .3 OK 7 .85 14 .5 OK 7 .76 14 .5 Female, Group: 643332 643340 643341 643359 643370 643404 643408 643435 643446 643466 VIII - OK OK OK OK OK OKOK OK OK OK 250 mg/kg - 7 .38 7 .72 7 .00 7 .58 8 .61 7 .84 7 .97 7 .62 8 .25 7 .56 Day 45 14 .0 15 .3 13 .1 14 .1 15 .0 15 .2 14 .7 14 .3 14 .7 14 .5 [ndivdLdual Hemat ology Value s HC T % MCV fL MiCH P9 MC]HC g/'3L 45. 5 46. 5 45. 2 46. 3 48. 8 46. 0 43. 7 46. 4 42. 9 44. 2 42. 4 45. 1 40. 1 43. 3 46. 9 45. 3 44. 5 43. 6 47. 3 44. 0 57.4 53.6 57.4 55.2 54.1 58.3 57.1 55.4 54.7 56.9 57.5 58.4 57.3 57.1 54.5 57.8 55.8 57.3 57.3 58.2 18 .7 17 .8 18 .9 18 .0 17 .6 19 .2 19 .5 18 .3 18 .4 18 .7 18 .9 19 .8 18 .7 18 .6 17 .4 19 .4 18 .5 18 .8 17 .8 19 .2 32 .6 33 .3 33 .0 32 .6 32 .6 32 .8 34 .1 33 .0 33 .7 32 .8 32 .9 33 .9 32 .6 32 .5 31 .9 33 .6 33 .1 32 .8 31 .0 32 .9 RDW ARET ?cl0^3/uL 11.5 11.7 12.4 11.2 11.9 11.9 10.8 11.3 11.4 13.3 12.0 12.4 12.4 12.6 12.0 11.6 11.6 12.0 12.7 12.2 203. 197. 229. 179. 198. 239. 146. 156. 192. 267. 177. 263. 223. 191. 249. 189. 174. 247. 241. 150. 744 .Company Sanitized. Does not conta H-24516: Subchronic Toxicity 90-Day Gavage Study in Rats with One-Generation Reproductive Evaluations Animal Number AMPR xlO ^3/uL ALYM Xl0^3/uL AMON xlO''3/UL Individual Hematology Values AEOS X10*3/UL ABAS xl0^3/uL ALUC xl0^3/uL ABLT xlO"3/uL AMSC xl0^3/uL PL xlO^/uL Female, Group: 643354 643361 643362 643374 643398 643406 643436 643463 643477 643486 11-0 NT NT NT NT NT NT NT NT NT NT mg/kg - Day 45 9.36 12.77 8.39 8.37 10.25 13.33 9.76 14.71 9.76 14.31 0.21 0.29 0.32 0.29 0.33 0.44 0.20 0.41 0.18 0.32 Female, Group: IV - 25 ing/kg - Day 45 643321 643324 643364 643380 643389 643390 643396 643410 643433 643458 NT NT NT NT NT O.'OO' NT NT NT NT NT 9.55 12.94 7.20 7.56 14.26 11.67 14.03 7.08 10.38 NT 0.16 0.33 0.26 0.22 0.16 0.40 0.28 0.23 0.24 0.33 0.24 0.19 0.11 0.10 0.23 0.24 0.15 0.16 0.16 NT 0.16 0.17 0.12 0.06 0.00 0.07 0.10 0,10 0.15 0.06 0.16 0.06 0.02 0.06 0.19 0.07 0.11 0.07 0.22 NT 0.12 0.11 0.09 0.09 0.00 0.15 0.11 0.04 0.13 0.24 0.29 0.17 0.09 0.11 0.30 0.26 0.22 0.14 0.27 NT 0.67 0.16 0.23 0.12 0.00 0.27 0.25 0.15 0.27 NT NT NT NT NT .NT NT NT NT NT NT NT NT NT NT 0.00 NT NT NT NT NT NT NT NT NT NT MT NT NT NT NT NT NT NT NT 0.00 NT NT NT NT 117 115 1060 1339 1092 RN 1294 RN RN RN N 990 1090 87 1171 953 1514 994 903 1239 745 Company Sanitized. I H-24516: Subchronic Toxicity 90-Day Gavage Study in Rats with One-Generation Reproductive Evaluations Animal Number AMPR xliO^/uL A LYM xl0*3 /UL AM ON xlO^/ UL Indiv idual. Heirlatologi' Values A:EOS 3cl0^3 /uL A BAS >cl0^3 /uL A LUC xl0*3 /UL ABLT x]1.0^3/uL AMSC x]L0^3/UL PL > clO^/u Female, Group: VI - 1()0 mg/k3 - Day 45 643322 643323 643366 643367 643392 643409 643461 643462 643472 643489 NT 8 .05 0. 31 0 .13 0 .05 0 .17 MT MT 13 .25 0. 40 0 .36 0 .14 0 .26 NT NT 10 .39 0. 25 0 .08 0 .18 0 .36 NT NT 9 .77 0. 32 0 .26 0 .13 0 .21 NT NT 10 .59 0. 32 0 .18 0 .14 0 .17 NT NT 7 .99 0. 14 0 .10 0 .05 0 .14 . NT NT 11 .96 0. 40 0 .19 0 .06 0 .13 NT NT 15 .65 0. 40 0 .22 0 .19 0 .38 NT NT 13 .16 0. 25 0 .19 0 .09 0 .19 NT NT 8 .26 0. 30 0 .10 0 .11 0 .20 NT Female, Group: VIII - 250 mg/kg - Day 45 643332 NT 9 .51 0. 17 0 .16 0 .08 0 .13 NT 643340 NT 12 .93 0. 39 0 .13 0 .12 0 .16 NT 643341 NT 10 .89 0. 44 0 .21 0 .08 0 .28 MT 643359 NT 9 .62 0. 41 0 .13 0 .07 0 .21 NT 643370 NT 7 .93 0. 34 0 .16 0 .11 0 .28 NT 643404 NT 12 .10 0. 22 0 .22 0 .08 0 .16 HT 643408 " NT 12 .92 0. 28 0 .21 0 .12 0 .25 NT 643435 NT 10 .81 0. 21 0 .14 0 .15 0 .26 NT 643446 NT 12 .63 0. 17 0 .18 0 .10 0 .29 NT 643466 NT 10 .54 0. 29 0 .23 0 .07 0 .21 NT NT 109 NT 110 NT 104 NT 125 NT 86 NT RN NT RN NT 114 NT 107 NT 108 NT 114 NT 101 NT RN NT 114 NT 115 NT 95 NT 99 NT 109 NT 89 NT 121 746 ^n^.D^no*""'21 Company H-24516: Subchronic Toxicity 90-Day Gavage Study in Rats with One-Generation Reproductive Evaluations Animal Number COND RBC xl0^6/uL HGB g/dL Female, Group: 643354 643361 643362 643374 643398 643406 643436 643463 643477 643486 11-0 OK OK OK OK OK OK OK OK OK OK mg/kg - Day 93 8.56 8.45 7.90 8.00 8.39 8.34 8.53 8.73 8.46 8.71 16.1 15.5 15.1 14.4 15.8 15.8 15.8 15.9 15.1 15.9 Female, Group: IV - 25 mg/kg - Day 93 643321 643324 643364 643380 643389 643390 643396 643410 643433 643458 NSR OK OK OK OK OK" OK OK OK OK NT 7.78 8.31 8.16 7.84 8.66 8.02 7.85 7.96 8.15 NT 15.4 16.4 15.3 14.7 15.6 14.5 14.6 15.2 14.7 Indivildual Hemat ology Value 8 HCT % MCV L MCH pg MCHC g/dL 48.0 47.5 45.2 43.8 49.5 48.8 49.4 48.7 46.6 48.8 NT 46.6 45.2 46.8 44.7 50.2 45.0 43.4 45.5 44.0 56.0 56.2 57.3 54.7 59.1 58.5 57.9 55.7 55.0 56.0 NT 59.9 54.4 57.4 57.0 58.0 56.1 55.3 57.1 54.0 18.8 18.4 19.1 18.1 18.9 19.0 18.5 18.2 17.9 18.2 NT 19.9 19.7 18.8 18.7 18.1 18.1 18.6 19.1 18.0 33.6 32.8 33.4 33.0 31.9 32.5 32.0 32.7 32.5 32.5 NT 33.2 36.3 32.7 32.8 31.2 32.3 33.6 33.4 33.4 RDW ARET xl0^3/uL 11.1 11.8 11.0 11.6 10.7 11.8 11.3 11.2 11.8 10.2 NT 11.1 10.7 11.5 11.2 11.9 10.9 11.2 11.7 11.5 115. 180. 144. 144. 207. 166. 148. 147. 174. 80. NT 188. 121. 127. 116. 173. 117. 173. 201. 193. 747 Company Sanitized. Does not c H-24516: Subchronic Toxicity 90-Day Gavage Study in Rats with One-Generation Reproductive Evaluations Animal Number COND RBC xl0^6/uL HGB g/dL Female, Group: VI - 100 ing/kg - Day 93 643322 643323 643366 643367 643392 643409 643461 643462 643472 643489 OK 7.87 14.7 OK 7.18 14.5 OK 7.94 14.7 OK 8.51 15.2 OK 9.48 16.3 OK 7.81 14.7 OK 7.74 14.9 OK 8.41 15.2 OK 8.56 15.3 OK 8.16 15.0 Female, Group: VIII - 250 nig/kg - Day 93 643332 643340 643341 643359 643370 643404 643408 643435 643446 643466 OK NSR OK OK OK OKOK OK OK OK 7.30 NT 7.78 8.02 8.19 7.66 8.13 8.16 7.61 7.50 13.6 NT 14.1 14.6 14.3 14.4 14.6 14.9 13.4 13.9 Indiv idual Hematology Value S HCT % MCV fL MCH PS MCHC g/dL 45.3' 48.6 44.7 46.6 51.5 43.6 44.0 46.4 46.6 45.1 42.2 NT 44.4 44.7 45.1 43.7 45.4 46.1 41.6 43.0 57.5 67.6 56.3 54.8 54.3 55.9 56.8 55.1 54.5 55.3 57.8 NT 57.2 55.7 55.1 57.0 55.8 56.5 54.7 57.3 18.6 20.2 18.5 17.9 17.2 18.9 19.2 18.0 17.9 18.4 18.7 NT 18.2 18.2 17.5 18.8 17.9 18.3 17.6 18.5 32.4 29.8 32.8 32.6 31.7 33.8 33.8 32.7 32.9 33.2 32.3 NT 31.8 32.6 31.8 32.9 32.1 32.4 32.1 32.4 RDW % ARE XlO"3/uL 11.9 173 19.2 725 11.6 171 11.0 122 11.4 161 11.7 206 11.0 145 11.3 119 11.0 150 12.4 220 12.5 161 NT N 12.5 197 12.6 157 14.8 229 11.5 165 11.4 155 11.5 187 11.9 140 12.1 156 748 Company Sanitized. Does not H-24516: Subchronic Toxicity 90-Day Gavage Study in Rats with One-Generation Reproductive Evaluations Animal Number ANPR xl(^3/uL A:LYM xlO^ /UL A]MON 100^3 /UL Individua]L Hematologi' Values3 A EOS 3cl0*3 /UL A BAS 3cl0*3 /UL A LUC 3(10^3 /uL ABLT x 10^3/uL AMSC x310^3/uL PLT 3cl0^3/uL Female, Group: II - 0 rng/kg - Day S!3 643354 NT 8 .38 0 .19 0 .40 0 .07 0 .12 NT 643361 NT 9 .60 0 .18 0 .26 0 .10 0 .14 NT 643362 NT 5 .97 0 .26 0 .11 0 .04 0 .05 NT 643374 NT 5 .55 0 .19 0 .13 0 .06 0 .05 NT 643398 NT 7 .47 0 .19 0 .09 0 .06 0 .08 NT 643406 NT 9 .69 0 .38 0 .22 0 .09 0 .23 .NT 643436 NT 7 .82 0 .19 0 .14 0 .06 0 .11 NT 643463 NT 9 .06 0 .19 0 .15 0 .12 0 .13 NT 643477 NT 9 .14 0 .19 0 .18 0 .06 0 .09 NT 643486 NT 9 .53 0 .15 0 .14 0 .09 0 .16 NT Female, Group: IV - 25 mg/kg - Day 93 643321 NT NT NT NT NT NT NT 643324 NT 8 .15 0 .13 0 .16 0 .12 0 .15 NT 643364 NT 6 .26 0 .23 0 .23 0 .03 0 .06 NT 643380 NT 5 .91 0 .27 0 .14 0 .07 0 .10 NT 643389 NT 6 .63 0 .19 0 .06 0 .03 0 .09 NT 643390 NT' 9 .85 0.45 0 .14 0 .07 0 .31 NT 643396 NT 7 .34 0 .30 0 .07 0 .12 0 .15 NT 643410 NT 10 .54 0 .17 0 .12 0 .08 0 .09 NT 643433 NT 6 .49 0 .16 0 .16 0 .04 0 .08 NT 643458 NT 9 .26 0 .23 0 .21 0 .11 0 .09 NT NT 1044 NT 1047 NT 1052 NT 1320 NT 967 NT 1054 NT 1129 NT 979 NT 787 NT 867 NT NT NT 958 NT RNV NT 872 NT 1159 NT 861 NT 1077 NT 1034 NT 1054 NT 1018 749 Company Sanitized. Does not contain H-24516: Subchronic Toxicity 90-Day Gavage Study in Rats with One-Generation Reproductive Evaluations Animal Number ANPR xll3*3/uL ALYM xl0^3/uL AMDN xl0*3/ uL Female, Group: VI - 1C)0 nig/kg - Day 93 643322 643323 643366 643367 643392 643409 643461 643462 643472 643489 NT 4.28 NT 9.80 NT 7.96 NT 6.03 NT 4.92 NT 6.58 NT 5.72 NT 9.65 NT 11.24 NT 7.71 0. 15 0. 32 0. 22 0. 22 0. 22 0. 23 0. 20 0. 38 0. 24 0. 40 Female, Group: VIII - 643332 NT 643340 NT 643341 NT 643359 NT 643370 NT 643404 NT- 643408 NT 643435 NT 643446 NT 643466 NT 250 mg/kg - 7.35 NT 7.71 8.24 5.56 10.58 8.31 7.23 10.90 7.86 Day 93 0. 14 NT 0. 35 0. 69 0. 17 0. 25 0. 32 0. 21 0. 16 0. 29 Individual. Hemat olog^' Values A EOS xl 0"3 /uL A BAS ; cl0*3 /uL A LUC ; cl0^3 /UL ABLT x]LO*3/uL 0 .14 0 .05 0 .04 NT 0 .40 0 .06 0 .14 NT 0 .10 0 .10 0 .12 NT 0 .23 0 .07 0 .12 NT 0 .20 0 .04 0 .06 NT 0 .26 0 .10 0 .08 .NT 0 .32 0 .04 0 .07 NT 0 .18 0 .10 0 .25 NT 0 .12 0 .09 0 .11 NT 0 .23 0 .09 0 .20 NT 0 .08 0 .05 0 .06 NT NT NT NT NT 0 .26 0 .04 0 .08 NT 0 .16 0 .05 0 .29 NT 0.25 0 .02 0 .09 NT 0 .16 0 .05 0 .13 NT 0 .20 0 .06 0 .12 NT 0 .15 0 .03 0 .12 NT 0 .16 0 .12 0 .14 NT 0 .24 0 .04 0 .20 NT AMSC x31.0^3/uL NT NT NT NT NT NT NT NT NT NT NT NT NT NT NT NT NT NT NT NT PLT ? cl0^3/uL RNV RNV 1083 1134 RNV 1132 RNV 1060 1305 996 1045 NT 1143 904 RNV RNV 1000 RNV 849 1231 750 Company Sanitized. Does not contain T H-24516: Subchronic Toxicity 90-Day Gavage Study in Rats with One-Generation Reproductive Evaluations Animal Number COMD RBC .Xl0^6/uL HGB g/dL Female, Group: 643330 643336 643377 643387 643405 643415 643425 643426 643448 643453 11-0 OK NSR OK OK OK OK OK OK OK OK mg/kg - Day 125 7.97 MT 7.80 8.33 7.87 7.57 8.00 7.28 8.49 8.25 14.9 NT 14.9 15.7 15.2 14.4 15.3 14.0 15.9 16.0 Female, Group: VIII - 250 mg/kg - Day 12S 643345 643347 643351 643358 643423 643441 643444 643456 643474 643481 OK OK OK OK OK CLOT OK OK OK OK 7.91 7.83 8.10 8.58 7.12 MT 8.58 7.38 8.34 8.13 14 .6 14.1 15.5 14.9 14 .0 NT 15.7 13.5 15.6 15.4 Individual Hemat:ology Value s HCT % MCV fL MCH pg MCHC g/dL 45.3 NT 44.6 47.0 48.2 43.6 46.4 42.0 47.9 46.3 44.0 43.0 46.6 44.6 42.2 NT 47.3 39.9 45.3 46.1 56.8 NT 57.2 56.4 61.2 57.7 58.0 57.6 56.5 56.1 55.6 54.9 57.6 52.0 59.2 NT 55.1 54.1 54.3 56.6 18.7 NT 19.2 18.8 19.4 19.1 19.1 19.3 18.7 19.4 18.4 18.0 19.1 17.3 19.6 NT 18.3 18.3 18.8 19.0 33.0 NT 33.5 33.3 31.6 33.0 33.0 33.5 33.1 34.5 33.1 32.7 33.1 33.4 33.2 NT 33.1 33.7 34.5 33.5 ROW AR % xl0^3/u 13.3 15 NT N 12.6 20 12.6 17 12.5 17 12.8 16 12.3 20 12.8 17 11.3 13 11.2 14 11.5 10 11.8 14 11.8 15 11.9 14 11.7 23 NT 12.0 15 11.8 12 11.9 13 11.0 11 751 Company Sanitized. Does not contain H-24516: Subchronic Tpxicity 90-Day Gavage Study in Rats with One-Generation Reproductive Evaluations Animal Number ANPR xll3^3/uL A:LYM xlO^ /UL A MON xl0^3 /UL Indiv idual. Hematcilogi' Valuesl A:EOS >cl0*3 /UL A BAS ?cl0^3 /UL A LUC x:10'3 /UL ABLT x 10^3/uL AMSC x]LO^/uL PL 3clO^/uL Female, Group: 11-0 mg/kg - Day 125 643330 643336 643377 643387 643405 643415 643425 643426 643448 643453 NT 5 .80 0 .12 0 .09 0 .01 0 .06 NT NT NT NT NT NT NT NT NT 4 .62 0 .20 0 .12 0 .06 0 .13 NT NT 5 .88 0 .14 0 .06 0 .03 0 .08 NT NT 9 .04 0 .30 0 .07 0 .02 0 .14 NT MT 5 .55 0 .27 0 .16 0 .04 0 .06 .NT NT 5 .45 0 .15 0 .10 0 .07 0 .09 NT NT 5 .07 0 .25 0 .05 0 .03 0 .08 NT NT 6 .52 0 .17 0 .06 0 .10 0 .08 NT NT 9 .72 0 .31 0 .16 0 .04 0 .09 NT Female, Group: VIII - 250 mg/kg - Day 125 643345 NT 4 .95 0 .20 0 .10 0 .05 0 .13 MT 643347 NT 7 .08 0 .16 0 .11 0 .06 0 .07 NT 643351 NT 6 .95 0 .14 0 .21 0 .03 0 .08 NT 643358 NT 4 .94 0 .26 0 .14 0 .02 0 .18 NT 643423 NT- 9 .16 0 .43 0 .16 0 .03 0 .12 NT 643441 tIT NT NT NT NT NT NT 643444 NT 4 .58 0 .58 0 .17 0 .02 0 .19 NT 643456 NT 5 .72 0 .30 0 .16 0 .07 0 .09 NT 643474 NT 5 .24 0 .27 0 .15 0 .03 0 .08 NT 643481 NT 4 .88 0 .23 0 .17 0 .01 0 .09 NT NT 958 NT N NT 985 NT 1376 NT 1158 NT 1256 NT 79 NT 1050 NT 1128 NT 68 NT 1212 NT 143 NT RN NT RN NT RN NT N NT 108 NT 103 NT RN NT 109 752 Company Sanitized. Does not co H-24516: Subchronic Toxicity 90-Day Gavage Study in Rats with One-Generation Reproductive Evaluations Animal Number NORM ANIS Individual Red Blood Cell Morphology Values MIC MAC POLY HYPO ECHI Male, Group: I - 0 nig/kg - Day 44 643143 643150 , 643185 643189 643204 643205 643235 643241 643288 643300 Male, Group: III - 25 mg/kg - Day 44 643173 643179 643180 643228 643240 643264 -'- " 643272 643290 643292 643308 ACAN TARG 753 Company Sanitized. Does not contai H-24516: Subchronic Toxicity 90-Day Gavage Study in Rats with One-Generation Reproductive Evaluations Animal Number NORM AMIS Individual Red Blood Cell Morphology Values MIC MAC POLY HYPO ECHI Male, Group: V - 100 m9/kg - Day 44 643175 1 1 643224 1 1 643243 1 2 664433225407 -- 1 1 -- 11 41 643257 643275 1 -- 1 1 643311 1 2 643314 1 1 643318 1 2 Male, Group: VII - 250 m9/kg - Day 44 643174 1 2 643193 1 3 643194 1 1 643201 1 1 643215 1 2 643252 1 2 664433226509 -- 1 1 -- 11 21 643298 1 1 643315 1 3 ACAN 1 1 2 3 ^ 1 1 2 2 1 3 2 ^ 3 2 2 2 1 2 2 TARG -- 754 Company Sanitized. Does not cont  H-24516: Subchronic Toxicity 90-Day Gavage Study in Rats with One-Generation Reproductive Evaluations Animal Number SPEC Male, Group: I - 0 mg/kg - Day 44 643143 643150 643185 643189 643204 643205 643235 643241 643288 643300 Male, Group: III - 25 mg/kg - Day 44 643173 643179 643180 643228 643240 643264 643272 643290 643292 643308 Individual Red Blood Cell Morphology Values 755 Company Sanitized. Does not conta ^ ^ H-24516: Subchronic Toxicity 90-Day Gavage Study in Rats with One-Generation Reproductive Evaluations Animal Number SPEC Male, Group: V - 100 nig/kg - Day 44 643175 643224 643243 643247 643250 643257 643275 643311 643314 643318 1-HEMOGLOBIN CRYSTAL 1-SPHEROCYTE Male, Group: VII - 250 mg/kg - 643174 643193 643194 643201 643215 - 643252 643259 643260 643298 643315 Day 44 Individual Red Blood Cell Morphology Values 756 Company Sanded- Does rol co H-24516: Subchronic Toxicity 90-Day Gavage Study in Rats with One-Generation Reproductive Evaluations Animal Number NORM ANIS . . Individual Red Blood Cell Morphology Values MIC MAC POLY HYPO ECHI Male, Group: I - 0 nig/kg - Day 91 643143 1 3 643150 1 2 -2-1121 643185 664433128094 -664433220355 -- 664433229481 -- 643300 -- 1 1 -- 3 1 Male, Group: III - 25 mg/kg - Day 91 1 -- 3 1 3 .3 1 3 3 1 3 1 3 643173 643179 643180 643228 643240 643264 --- 643272 -- 643290 643292 643308 1 3 1 1 1 3 1 3 1 3 2 3 1 -- 3 1 3 1 2 ACAN 3 1 -3 3 4 3 3 3 2 1 1 2 3 2 3 -3 3 3 TARG 757 H-24516: Subchronic Toxicity 90-Day Gavage Study in Rats with One-Generation Reproductive Evaluations Animal Number NORM ANIS Individual Re<i B1.ood Ce;LI Morpholo;N Va lues MIC MAC POLY HYPO ECHI Male, Group: V - 100 mg/kg - Day 91 643175 ' -- -- -- -- -- 643224 -- -- -- 643243 -- -- -- -- 643247 -- -- -- -- 643250 -- -- -- -- 643257 -- -- -- -- 643275 -- -- -- -- 643311 -- -- -- 643314 -- -- -- -- 643318 -- -- -- -- 1 -- 3 1 -- 3 1 -- 1 1 -- 2 1 -- 3 . 1 -- 1 1 -- 3 1 -- 3 1 -- 3 Male, Group: VII - 250 mg/kg - Day 91 643174 2 1 1 2 -- 3 643193 -- -- -- -- 1 -- 2 643194 -- 2 1 1 2 -- 3 643201 -- 1 1 -- 1 -- 2 643215 -- . -- -- -- 1 -- 2 643252 -. 643259 -- 2 2 2 -- 1 1 2 -- 2 -- 3 2 643260 -- -- -- 1 -- 3 643298 -- 1 1 -- 1 -- 2 643315 -- -- -- -- 2 -- 3 ACAN -3 3 -2 3 1 3 3 3 3 3 3 3 3 3 3 3 3 3 TARG ------ 758 Company Sanitized. Does not contain H-24516: Subchronic Toxicity 90-Day Gavage Study in Rats with One-Generation Reproductive Evaluations Animal Number SPEC Male, Group: I - 0 mg/kg - Day 91 643143 643150 643185 643189 643204 643205 643235 643241 643288 643300 1-POIKILOCYTOSIS 1-HEMOGLOBIN CRYSTAL 1-SPHEROCYTE Male, Group: III - 25 mg/kg - Day 91 643173 643179 643180 643228 643240 643264 643272 643290 643292 643308 1 -POIKILOCYTOSIS Individual Red Blood Cell Morphology Values 759 Company Sanitized. Does not contai H-24516: Subchronic Toxicity 90-Day Gavage Study in Rats with One-Generation Reproductive Evaluations Animal Number SPEC Male, Group: V - 100 mg/kg - Day 91 643175 643224 643243 643247 643250 643257 643275 643311 643314 643318 1-POIKILOCYTOSIS Male, Group: VII - 250 mg/kg - Day 91 643174 643193 643194 643201 643215 643252 643259 643260 643298 643315 1-POIKILOCYTOSIS 1 -POIKILOCYTOSIS 1 -POIKILOCYTOSIS Individual Red Blood Cell Morphology Values 760 Company Sanitized. Does not contain H-24516: Subchronic Toxicity 90-Day Gavage Study in Rats with One-Generation Reproductive Evaluations Animal Number NORM ANIS In.dividual Rfid Blood Ce:11 Morpholoc3y Va lues MIC MAC POLY HYPO ECHI Male, Group: 1-0 nig/kg - Day 125 643162 .. -- 643172 -- 1 1 -- 643195 -- -- -- -- 643226 -- 1 1 -- 643237 -- 1 1 -- 643246 -- 1 1 -- 643253 -- 1 1 -- 643262 -- -- -- -- 643303 -- 1 1 -- 643304 -- -- -- -- Male, Group: VII - 250 nig/kg - Day 125 643151 643165 -- -- -- 643220 1 1 -- 643225 -- 1 1 -- 643234 -- -- -- -- 643236 -- 2 1 1 643258 -- 1 1 -- 643266 -- 1 1 -- 643296 -- 1 -- 1 643316 -- 1 . 1 -- 1 -- 1 -- 1 1 -- 1 1 -- 1 1 -- 1 1 -- 2 1 -- 2 1 -- 1 1 -- 1 1 -- 1 1 1 1 -- 1 1 -- 2 1 -- -- 1 -- 1 1 -- 1 1 -- -- 1 -- 1 1 -- 2 1 -- 2 ACAN 1 2 1 -1 1 3 1 1 -- 1 1 3 1 -3 1 3 1 2 TARG -------------------- 761 Company Sanitized. Does not conta ^ H-24516: Subchrpnic Toxicity 90-Day Gavage Study in Rats with One-Generation Reproductive Evaluations Animal Number SPEC Male, Group: I - 0 nig/kg - Day 125 643162 643172 643195 643226 643237 643246 643253 643262 643303 643304 1-SPHEROCYTE Male, Group: VII - 250 mg/kg - Day 125 643151 643165 643220 643225 643234 643236 643258 643266 643296 643316 1-POI-KILOCYTOSIS Individual Red Blood Cell Morphology Values 762 C.n^an,Si>,ze<.O.e. H-24516: Subchrpnic Toxicity 90-Day Gavage Study in Rats with One-Generation Reproductive Evaluations Animal Number NORM AMIS Individual Red Blood Cell Morphology Values MIC MAC POLY HYPO ECHI Female, Group; II - 0 nig/kg - Day 45 ' 643354 643361 -- 1 1 1 1 643362 643374 643398 643406 643436 643463 --11 1 1 1 4 1 1 1 .3 1 2 1 3 643477 1 2 643486 1 1 Female, Group: IV - 25 mg/kg - Day 45 643321 643324 643364 643380 643389 -.- - 643390 643396 643410 643433 643458 - - - - 1 2 1 2 1 3 1 2 1 1 1 4 1 1 1 2 1 1 ACAN 1 1 -2 -2 ^ 2 2 1 1 2 2 ^ -2 ^ -1 TARG 763. Company Sanitized. Does not cont H-24516: Subchronic Toxicity 90-Day Gavage Study in Rats with One-Generation Reproductive Evaluations Animal Number NORM ANIS Individual Red Blood Cell Morphology Values MIC MAC POLY HYPO ECHI Female, Group: VI - 100 mg/kg - Day 45 643322 643323 643366 643367 643392 643409 643461 643462 643472 643489 -- 1 3 -- 1 2 -- 1 1 -- 1 2 -- 1 2 -- 1 .4 -- 1 3 -- 1 3 -- 1 2 -- 1 3 Female, Group: VIII - 250 ing/kg - Day 45 643332 643340 643341 643359 643370 643404 --- 643408 643435 643446 643466 - 1 1 -- 1 2 -- 1 3 -- 1 2 -- 1 3 -- 1 3 -- 1 3 ' 1 3 -- 1 4 -- 1 3 ACAN 1 1 -2 2 2 2 1 2 1 ] 1 2 1 2 3 1 2 1 TARG 2 764 Company Sanitized. Does not c H-24516: Subchronic Toxicity 90-Day Gavage Study in Rats with One-Generation Reproductive Evaluations Animal Number SPEC Female, Group: 643354 643362 643361 643374 643398 643406 643436 643463 643477 643486 II - 0 ing/kg - Day 45 2-HEMOGLOBIN CRYSTAL Female, Group: IV - 25 mg/kg - Day 45 643321 643324 643364 643380 643389 643390 643396 643410 643433 643458 - 1-HEMOGLOBIN CRYSTAL . Individual Red Blood Cell Morphology Values 765 Company Sanitized. Does not contai H-24516: Subchronic Toxicity 90-Day Gavage Study in Rats with One-Generation Reproductive Evaluations Animal Number SPEC Female, Group; VI - 100 ing/kg - Day 45 643322 643323 643366 643367 643392 643409 643461 643462 643472 643489 2-HEMOGLOBIN CRYSTAL 1-HEMOGLOBIN CRYSTAL 2-HEMOGLOBIN CRYSTAL Female, Group: VIII - 250 mg/kg - Day 45 643332 643340 643341 643359 643370 643404 643408 643435 643446 643466 1-HEMOGLOBIN CRYSTAL Individual Red Blood Cell Morphology Values 766 Company Sanitized. Does not con H-24516: Subchronic Toxicity 90-Day Gavage Study in Rats with One-Generation Reproductive Evaluations Animal Number NORM AMIS Individual Red Blood Cell Morphology Values MIC MAC POLY HYPO ECHI ACAN Female, .Group: II - 0 mg/kg - Day 93 643354 643361 643362 643374 643398 643406 643436 643463 643477 643486 Female, Group: IV - 25 mg/kg - Day 93 643321 643324 643364 643380 643389 643390 643396 643410 643433 643458 --- 1 1 1 -- 1 1 1 1 1 1 1 2 - 1 ^ -- 2 2 1 - 3 2 1 -- 1 -- 2 -- 2 -- - - 1 1 1 1 1 1 1 1 1 1 -- 2 1 1 2 1 1 1 -- 1 -- 1 -- 2 -- -- . -- TARG -- - 767 Company Sanitized. Does not conta ^ H-24516: Subchronic Toxicity 90-Day Gavage Study in Rats with One-Generation Reproductive Evaluations Animal Number NORM AMIS Individual Red Blood Cell Morphology Values MIC MAC POLY HYPO ECHI Female, Group: VI - 100 mg/kg - Day 93 643322 ' 643323 643366 643367 643392 643409 643461 643462 643472 643489 --- -11 Female, Group: VIII - 2SO mg/kg - Day 93 643332 643340 643341 643359 643370 643404 643408 643435 643446 643466 1 -- 1 . 2 -- 2 -- 1 -- 1 -- 1 -- 3 -- 1 -- .3 -- 1 -- 2 -- 1 -- 2 -- 1 -- 1 -- 1 -- 2 -- 1 -- 2 -- 1 1 -- -- -- -- -- 1 -- 2 -- 1 -- 2 -- 1 -- 2 -- 1 -- 3 -- 1 -- 3 -- 1 -- 4 -- 1 -- 2 -- 1 -- 3 ACAN TARQ -^ --^ 1 2 1 --^ 2 - - -3 1 2 1 1 2 -- 1 . 3 768 Company Sanitized. Does not contain ^ _ H-24516: Subchrpnic Toxicity 90-Day Gavage Study in Rats with One-Generation Reproductive Evaluations Animal Number SPEC Female, Group: 643354 643361 643362 643374 643398 643406 643436 643463 643477 643486 II - 0 mg/kg - Day 93 1-POIKILOCYTOSIS Female, Group: IV - 25 mg/kg - Day 93 643321 643324 643364 643380 643389 - 643390 643396 643410 643433 643458 Individual Red Blood Cell Morphology Values 769 Company Sanitized. Does not contain H-24516: Subchronic Toxicity 90-Day Gavage Study in Rats with One-Generation Reproductive Evaluations Animal Number SPEC Female, Group: VI - 643322 643323 643366 643367 643392 643409 643461 643462 643472 643489 100 mg/kg - Day 93 Female, Group: VIII - 250 mg/kg - 643332 643340 643341 643359 643370 643404 643408 643435 643446 643466 ' - 1-SPHEROCYTE Day 93 Individual Red Blood Cell Morphology Values 770 Company Sanitized. Does not conta H-24516: Subchronic Tpxicity 90-Day Gavage Study in Rats with One-Generation Reproductive Evaluations Animal Number NORM ANIS In dividual Rtid Blood Ce:LI Morpholocjy Va lues MIC MAC POLY HYPO ECHI Female, Group: 11-0 mg/kg - Day 125 643330 -- 1 -- 2 643336 -- -- -- -- -- -- -- 643377 -- -- -- -- 1 -- 1 643387 -- -- -- -- 1 -- 1 643405 -- -- -- -- 1 -- 2 643415 -- -- -- -- 1 -- ..2 643425 -- 1 1 -- 1 -- 1 643426 -- -- -- -- 1 -- 1 643448 -- -- -- -- 1 -- -- 643453 -- -- -- -- 1 -- Female, Group: VIII - 250 mg/kg - Day 125 643345 -- 1 -- -- 643347 -- 1 1 -- 1 -- 1 643351 -- -- -- -- 1 -- 2 643358 -- -- -- -- 1 -- 1 643423 643441 -- -"- --- --- --- 1 -- --- 2 -- 643444 -- -- -- -- 643456 -- -- -- -- 1 -- -- 1 -- 1 643474 -- -- -- -- 1 -- 1 643481 -- -- -- -- 1 -- -- ACAM 2 ---- 2 1 1 --- -1 --------- TARG -------------------- 771 Company Sanitized. Does not contain  H-24516: Subchronic Toxicity 90-Day Gavage Study in Rats with One-Generation Reproductive Evaluations Animal Number SPEC Individual Red Blood Cell Morphology Values Female, .Group; II - 0 ing/kg - Day 125 643330 643336 643377 643387 643405 643415 643425 643426 643448 643453 Female, Group: 643345 643347 643351 643358 643423 643441 643444 643456 643474 643481 VIII - 250 mg/kg - - - Day 125 772 Company Sanitized. Does not cont H-24516: Subchronic Toxicity 90-Day Gavage Study in Rats with One-Generation Reproductive Evaluations Animal Number NORM Individual White Blood Cell / Platelet Morphology Values SM DB PC GP BP TOX VC Male, Group: I 0 mg/kg - Day 44 643143 643150 643185 643189 643204 643205 643235 643241 643288 643300 NORMAL NORMAL NORMAL NORMAL NORMAL NORMAL NORMAL NORMAL NORMAL Male, Group: 643173 643179 643180 643228 643240 643264 643272 643290 643292 643308 III - 25 mg/kg - NORMAL NORMAL NORMAL NORMAL NORMAL NORMAL NORMAL NORMAL NORMAL Day 44 SPEC DECR ADEQ 773 ""WT 8----d. Doe. M H-24516: Subchronic Toxicity 90-Day Gavage Study in Rats with One-Generation Reproductive Evaluations Animal Number NORM Individual White Blood Cell / Platelet Morphology Values SM DB PC GP BP TOX VC Male, Group: V - 100 mg/kg - Day 44 643175 643224 643243 643247 643250 643257 643275 643311 643314 643318 NORMAL NORMAL NORMAL NORMAL NORMAL NORMAL NORMAL NORMAL Male, Group: 643174 643193 643194 643201 643215 643252 643259 643260 643298 643315 VII - 250 mg/kg - NORMAL NORMAL NORMAL NORMAL NORMAL NORMAL NORMAL NORMAL Day 44 SPEC UTD DECR DECR UTD 774 Company Sanitized. Does not contain H-24516: Subchronic Toxicity 90-Day Gavage Study in Rats with One-Generation Reproductive Evaluations Animal Number NORM Individual White Blood Cell / Platelet Morphology Values SM DB PC GP BP TOX VC Male, Group: I - 0 ing/kg - Day 91 643143 643150 643185 643189 643204 643205 643235 643241 643288 643300 NORMAL NORMAL NORMAL NORMAL NORMAL NORMAL NORMAL Male, Group: 643173 643179 643180 643228 643240 643264 643272 643290 643292 643308 III - 25 mg/kg - NORMAL NORMAL NORMAL NORMAL NORMAL NORMAL NORMAL NORMAL NORMAL Day 91 SPEC UTD DECR 775 Company Sanitized. Does not conta H-24516: Subchronic Toxicity 90-Day Gavage Study in Rats with One-Generation Reproductive Evaluations Animal Number NORM Individual White Blood Cell / Platelet Morphology Values SM DB PC GP BP TOX VC Male, Group: V - 100 mg/kg - Day 91 643175 643224 643243 643247 643250 643257 643275 643311 643314 643318 NORMAL NORMAL NORMAL NORMAL NORMAL NORMAL NORMAL NORMAL Male, Group: VII - 250 mg/kg - 643174 643193 643194 643201 643215 643252 643259 643260 643298 643315 NORMAL NORMAL NORMAL NORMAL NORMAL NORMAL NORMAL Day 91 SPEC DECR DECR UTD DECR 776 Company Sanitized. Does noi contain H-24516: Subchronic Toxicity 90-Day Gavage Study in Rats with One-Generation Reproductive Evaluations Animal Number NORM Individual White Blood Cell / Platelet Morphology Values SM DB PC GP BP TOX VC Male, Group; I - 0 mg/kg - Day 125 643162 643172 643195 643226 643237 643246 643253 643262 643303 643304 NORMAL NORMAL NORMAL NORMAL NORMAL NORMAL NORMAL Male, Group: VII - 250 mg/kg - Day 125 643151 643165 643220 643225 643234 643236 643258 643266 643296 643316 NORMAL NORMAL NORMAL NORMAL NORMAL f NORMAL NORMAL NORMAL NORMAL SPEC ADEQ P UTD P DECR P ADEQ P 777 Company Sanitized. Does not contain H-24516: Subchronic Toxicity 90-Day Gavage Study in Rats with One-Generation Reproductive Evaluations Animal Number NORM Individual White Blood Cell / Platelet Morphology Values SM DB PC GP BP TOX VC Female, Group: II - 0 ing/kg - 643354 643361 643362 643374 643398 643406 643436 643463 643477 6434B6 NORMAL NORMAL NORMAL NORMAL NORMAL NORMAL Day 45 Female, Group: IV - 25 mg/kg - 643321 643324 643364 643380 643389 643390 643396 643410 643433 643458 NORMAL NORMAL NORMAL NORMAL NORMAL NORMAL NORMAL NORMAL NORMAL Day 45 SPEC ADEQ UTD DECR ADEQ 778. Company Sanitized. Does not contai H-24516: Subchronic Toxicity 90-Day Gavage Study in Rats with One-Generation Reproductive Evaluations Animal Number NORM Individual White Blood Cell / Platelet Morphology Values SM DB PC GP . BP TOX VC Female, Group: VI - 100 mg/kg - Day 45 643322 643323 643366 643367 643392 643409 643461 643462 643472 643489 NORMAL NORMAL NORMAL NORMAL NORMAL NORMAL NORMAL NORMAL Female, Group: VIII 643332 643340 643341 643359 643370 643404 643408 643435 643446 643466 NORMAL NORMAL NORMAL NORMAL NORMAL NORMAL NORMAL NORMAL NORMAL 250 mg/kg - Day 45 SPEC ADEQ ADEQ ADEQ 779 Company Sanitized. Does not conta H-24516: Subchronic Toxicity 90-Day Gavage Study in Rats with One-Generation Reproductive Evaluations Animal Number NORM Individual White Blood Cell / Platelet Morphology Values SM DB PC GP BP TOX . VC Female, Group: II - 0 mg/kg - 643354 643361 643362 643374 643398 643406 643436 643463 643477 643486 NORMAL NORMAL NORMAL NORMAL NORMAL NORMAL NORMAL NORMAL NORMAL NORMAL Day 93 Female, Group; IV - 25 mg/kg - 643321 643324 643364 643380 643389 643390 643396 643410 643433 643458 NORMAL NORMAL NORMAL NORMAL NORMAL NORMAL NORMAL NORMAL Day 93 SPEC UTD 780 CompanySam-feed. Does not con H-24516: Subchronic Toxicity 90-Day Gavage Study in Rats with One-Generation Reproductive Evaluations Animal Number NORM Individual white Blood Cell / Platelet Morphology Values SM DB PC GP BP TOX VC Female, Group: VI - 100 mg/kg - Day 93 643322 643323 643366 643367 643392 643409 643461 643462 643472 643489 NORMAL NORMAL NORMAL NORMAL NORMAL NORMAL Female, Group: VIII 643332 643340 643341 643359 643370 643404 643408 643435 643446 643466 NORMAL NORMAL NORMAL NORMAL NORMAL NORMAL 250 mg/kg - Day 93 SPEC UTD UTD UTD UTD UTD ADEQ UTD 781 CompanySanitized. Does not co H-24516: Subchronic Toxicity 90-Day Gavage Study in Rats with One-Generation Reproductive Evaluations Animal Number NORM Individual White Blood Cell / Platelet Morphology Values SM DB PC GP BP TOX VC Female, Group: II - 0 ing/kg - 643330 643336 643377 643387 643405 643415 643425 643426 643448 643453 NORMAL NORMAL NORMAL NORMAL NORMAL NORMAL NORMAL NORMAL NORMAL Day 125 Female, Group: VIII - 643345 643347 643351 643358 643423 643441 643444 643456 643474 643481 NORMAL NORMAL NORMAL NORMAL NORMAL 250 mg/k9 - Day 125 SPEC DECR DECR UTD UTD 782 Company Sanitized. Does not co H-24516: Subchronic Toxicity 90-Day Gavage Study in Rats with One-Generation Reproductive Evaluations Animal Number PHEM FLIP PICT Male, Group: I - 0 mg/'kg - Day 91 643143 643150 643185 643189 643204 643205 643235 643241 643288 643300 NONE NONE NONE NONE NONE NONE NONE NONE NONE NONE NONE NONE NONE NONE KONE NONE NONE NONE NONE NONE Male, Group: 643173 643179 643180 643228 643240 643264 643272 643290 643292 643308 III - 25 mg/kg - Day 91 NONE NONE NONE NONE NONE NONE NONE NONE NONE NONE NONE NONE NONE NONE NONE NONE NONE NONE NONE NONE NONE NONE NONE NONE NONE NONE NONE NONE NONE NONE NONE NONE NONE NONE NONE NONE NONE NONE NONE NONE Individ.ual 'Coagulation Values PT 8 ec AP'TT s ec 14 .7 15 .6 15 .2 16 .2 15 .7 14 .4 14 .6 15 .1 14 .3 16 .5 14 .8 14 .5 15 .2 14 .3 14 .6 14 .8 14 .5 15 .3 14 .5 14 .1 17 .5 17 .9 16 .8 21 .9 18 .0 15 .0 20 .2 22 .7 16 .5 20 .0 13 .6 13 .1 19 .4 17 .0 18 .4 15 .7 16 .3 18 .7 14 .3 16 .1 783 Company Sanitized. Does n H-24516: Subchronic Toxicity 90-Day Gavage Study in Rats with One-Generation Reproductive Evaluations Animal Number PHEM FLIP PICT Male, Group: V - 100 m g/kg - Day 9]L 643175 643224 643243 643247 643250 643257 643275 643311 643314 643318 NSR NONE NONE NONE NONE NONE NONE NONE NONE NONE NT NONE NONE NONE NONE NONE NONE NONE NONE NONE NT NONE NONE NONE NONE NOME NONE NONE NONE NONE Male, Group: VII - 250 mg/kg - Day 91 643174 643193 643194 643201 643215 643252 643259 643260 643298 643315 NONE NONE NONE NONE NONE . TRACE NONE NONE NONE NONE NONE NONE NONE NONE NONE NONE NONE NONE NONE NONE NONE NONE NONE NONE NONE NONE NONE NONE NONE NONE Indiv:Ldual Coagulation Values PT s ec APIT sec NT 14 .7 14 .3 14 .7 16 .6 15 .2 16 .5 15 .5 15 .0 14 .1 15 .6 15 .2 14 .7 15 .0 16 .7 15 .8 15 .5 16 .4 14 .9 14 .9 K[T 14. 5 13. 5 15. 7 18. 7 13. 2 18. 7 15. 7 17. 5 14. 8 18. 6 17. 3 16. 1 17. 0 16. 4 17. 4 16. 2 16. 2 16. 0 16. 4 784 Company Sanitized. Does not conta H-24516: Subchronic Toxicity 90-Day Gavage Study in Rats with One-Generation Reproductive Evaluations Animal Number PHEM PLIP PICT Female, Group: 11-0 mg/kg - Day 93 643354 643361 643362 643374 643398 643406 643436 643463 643477 643486 NONE SMALL NONE NONE NONE NONE TRACE NONE TRACE TRACE NONE NONE NONE NONE NONE NONE NONE NONE NONE NONE NONE NONE NONE NONE NONE NONE NONE NONE NONE NONE Female, Group: IV - 25 mg/kg - Day 93 643321 643324 643364 6433BO 643389 643390 643396 643410 643433 643458 NSR NONE NONE TRACE NONE NONE NONE NONE NONE NONE NT NONE NONE NONE NONE NONE NOME NONE NONE NONE NT NONE NONE NONE NONE NONE NONE NONE NONE NONE Individijal Coagulation Values PT APTT sec sec 14.7 NT 14.2 13.4 14.8 14.9 13.9 13.7 15.0 16.0 NT 14.2 14.3 14.3 14.7 14.0 14.0 14.4 14.7 14.8 17.9 NT 16.6 15.0 17.8 16.5 15.9 16.3 18.2 19.6 NT 16.6 15.9 12.9 15.9 17.1 17.7 15.3 14.8 16.3 785 Company Sanitized. Does not contai H-24516: Subchronic Toxicity 90-Day Gavage Study in Rats with One-Generation Reproductive Evaluations Animal Number PHEM FLIP PICT Female, Group: VI - 100 mg/kg - Day 93 643322 643323 643366 643367 643392 643409 643461 643462 643472 643489 NONE HONE NOME NONE NONE NONE NONE NONE NONE NONE NONE NONE NONE NONE NONE NONE NONE NONE NONE NONE NONE NONE NONE NONE NONE NONE NONE NONE NONE NONE Female, Group: 643332 643340 643341 643359 643370 643404 643408 643435 643446 643466 VIII - NONE MSR NONE NONE NONE NONE NONE NONE NONE NONE 250 mg/kg - NONE NT NONE NONE NONE NONE NONE NONE NONE NONE Day 93 NONE NT NONE NONE NONE TRACE NONE NONE NONE NONE Indiv idual Coagulation Values PT APTT sec sec 13.8 14.4 14.1 14.7 14.6 15.3 14.4 15.2 13.6 14.5 13.7 NT 13.9 14.1 13.4 14.0 13.6 14.6 15.0 14.6 13.8 17.3 17.3 17.1 14.4 15.9 14.3 14.3 17.1 12.9 14.7 NT 15.3 16.2 14.6 14.1 16.7 13.7 12.8 17.5 786 Company Sanitized. Does not contain T H-24516: Subchronic Toxicity 90-Day Gavage Study in Rats with One-Generation Reproductive Evaluations Animal Number SHEM SLIP SICT Individual Serum and Plasma Chemistry Values AST IU/L ALT IU/L SDK IU/L ALKP IU/L Male, Group: I 0 mg/kg - Day 44 643143 NONE NONE NONE 97 643150 TRACE NONE NONE 84 643185 NONE NONE NONE 82 643189 NONE NONE NONE 79 643204 NONE NONE NONE 69 643205 NOME NONE NONE 70 643235 NONE NONE NONE 66 643241 NONE NONE NONE 71 643288 NONE NONE NONE 74 643300 NONE NONE NONE 90 Male, Group: III - 25 mg/kg - Day 44 643173 TRACE NONE NONE 72 643179 SMALL NONE NONE 81 643180 NONE NONE NONE 71 643228 NONE NONE NONE 104 643240 NONE . NONE NONE 79 643264 SMALL NONE NONE 94 643272 TRACE NONE NONE 90 643290 NONE NONE NONE 74 643292 NONE NONE NONE 70 643308 NONE NONE NONE 100 37 13 .3 128 33 19 .4 184 28 17 .3 113 27 26 .0 144 30 20 .3 87 31 15 .6 123 23 15 .4 153 30 25 .0 157 28 15 .6 91 31 20 .0 158 40 21 .1 144 31 16 .2 165 33 14 .3 109 24 20 .6 104 32 12 .3 125 26 11 .9 100 36 17 .6 176 35 27 .4 204 38 18 .4 175 34 18 .9 139 BILI mg/dL <0. 10 0. 10 <0. 10 <0. 10 0. 12 0. 11 0. 10 0. 12 <0. 10 0. 13 <0 .10 0 .11 <0 .10 0 .15 <0 .10 0 .10 <0 .10 0 .12 <0 .10 0 .15 BUN mg/dL 15 13 14 16 13 12 15 12 17 14 12 16 15 15 15 12 16 14 14 12 787 Company SanRfzed. Does not contain H-24516: Subchronic Toxicity 90-Day Gavage Study in Rats with One-Generation Reproductive Evaluations Animal Number SHEM SLIP SICT Individual Serum and Pla sma Chemi stry Values AST IU/L ALT IU/L SDH IU/L ALKP IU/L BILI mg/dL Male, Group: V - 100 mg/kg - Day 44 643175 643224 643243 643247 643250 643257 643275 643311 643314 643318 MODERATE TRACE MODERATE NONE TRACE NONE SMALL TRACE NONE NONE NONE NONE NONE NONE NONE NONE NONE NONE NONE NONE NONE NONE NONE NONE NONE NONE NONE NONE NONE NONE Male, Group: VII - 250 ing/kg - Day 44 643174 643193 643194 643201 643215 643252 643259 643260 643298 643315 NONE NONE TRACE MODERATE NONE NONE TRACE NONE NONE TRACE NONE NONE NONE NONE NONE NONE NONE NONE NONE NONE NONE NONE NONE NONE NONE NONE NONE NONE NONE NONE NT-HEMOL 80 NT-HEMOL 85 75 80 65 76 67 76 NT-HEMOL 32 NT-HEMOL 16 33 35 29 26 24 31 74 99 78 NT-HEMOL 86 86 104 63 64 88 31 31 46 NT-HEMOL 23 35 46 27 26 32 15.7 14.3 20.9 18.2 22.9 16.9 17.5 17.5 16.9 21.0 NT-HEMOL 141 NT-HEMOL 134 157 141 202 153 162 159 NT-HEMOL <0.10 NT-HEMOL <0.10 <0.10 0.12 <0.10 0.12 0.12 <0.10 28.4 11.6 20.8 6.2 16.1 20.1 20.9 13.9 14.0 22.1 187 185 225 NT-HEMOL 191 157 240 166 165 152 0.10 <0.10 <0.10 NT-HEMOL <0.10 <0.10 <0.10 <0.10 <0.10 <0.10 BUN mg/dL 14 15 16 19 13 17 14 14 14 15 14 17 14 16 13 12 13 13 14 13 788 Company Sanitized. Does not co H-24 516: Subchronic Toxicity 90-Day Gavage Study in Rats with One-Generation Reproductive Evaluations Animal Number TRIG mg/dL ( 3LUC me3/dL TP g/dL Inciividiial Sei:um arid Pla sma C1-lemist ry Vailjes A LB g/ dL GLOB g/ dL CALC mg/idL IPH S mg/d,L Male, Group: 1-0 mg/kg - IDay 44 643143 65 104 6.4 3 .9 2 .5 10 .2 8. 8 643150 78 93 6.0 3 .9 2 .1 10 .4 8. 2 643185 41 111 6.5 4 .1 2 .4 10 .5 8. 2 643189 113 145 6.4 4 .0 2 .4 10 .9 9. 4 643204 177 106 6.6 4 .3 2 .3 11 .0 8. 4 643205 41 97 6.8 4.2 2 .6 10 .8 8.4 643235 89 109 6.5 4 .0 2 .5 10 .8 7. 9 643241 217 99 6.9 4 .4 2 .5 11 .5 9. 1 643288 79 105 6.7 4 .0 2 .7 10 .8 7. 7 643300 65 135 6.7 4 .4 2 .3 11 .0 10. 0 Male, Group: III - 25 mg/kg - Day 44 643173 126 96 6.5 4 .3 2 .2 11 .2 9. 0 643173 81 96 6.4 4 .0 2 .4 10 .5 9. 6 643180 124 120 6.4 3 .9 2 .5 11 .1 9. 2 643228 122 129 6.6 4 .1 2 .5 11 .1 9. 6 643240 56 ' 89 6.1 4 .0 2 .1 10.4 8. 9 643264 56 101 6.8 4 .2 2 .6 10.4 8. 1 643272 46 96 6.7 4 .3 2.4 10 .5 9. 2 643290 101 98 7.1 4 .6 2 .5 11 .2 9. 3 643292 97 107 6.8 4 .5 2 .3 11 .6 9. 1 643308 94 109 6.5 4 .2 2 .3 10 .6 8. 6 i NA mmol /L 143 .3 144 .3 147 .0 145 .9 141 .7 144 .4 142 .1 147 .7 143 .8 144 .5 144 .6 145 .2 141 .7 143 .3 143 .7 143 .7 143 .7 142 .4 144 .1 143 .0 K mmo 1/L 6 .30 6 .55 6 .43 5 .65 5 .95 6 .15 5 .34 6 .16 5 .54 6 .13 5 .82 6 .45 5 .88 6 .29 5 .86 5 .89 6 .31 5 .97 5 .88 6 .15 789 Company Sanded. Does not H-24516: Subchronic Toxicity 90-Day Gavage Study in Rats with One-Generation Reproductive Evaluations Animal Number TRIG ing/dL GLUC mg/dL TP g/dL Individual Serum and Pla sma C1-iemi a try Values ALB g/dL GLOB 9/dL CALC mg/idL IPHS mg/dL Male, Group : V - 100 me3/k9 - Day 44 643175 643224 643243 643247 643250 643257 643275 643311 643314 643318 NT-HEMOL 35 NT-HEMOL 122 28 65 52 86 85 130 104 NT-HEMOL 110 6.1 123 NT-HEMOL 112 6.6 88 6.5 109 7.2 126 6.8 103 6.8 103 6.7 106 7.0 Male, Group : VII - 250 mg/kg - Day 44 643174 643193 643194 643201 643215 643252 643259 643260 643298 643315 152 39 42 NT-HEMOL 57 " 16 35 55 47 37 147 7.8 103 7.6 95 7.5 107 NT-HEMOL 101 6.8 116 6.9 107 7.4 106 7.1 106 7.6 133 6.7 NT-HEMOL 4.1 NT-HEMOL 3.2 4.4 4.6 4.5 4.3 4.4 4.6 5.1 5.2 5.2 NT-HEMOL 4.7 4.8 5.1 4.9 5.2 4.5 NT-HEMOL 2.0 NT-HEMOL 3.4 2.1 2.6 2.3 2.5 2.3 2.4 2.7 2.4 2.3 NT-HEMOL 2.1 2.1 2.3 2.2 2.4 2.2 10 .7 9 .9 11 .2 11 .1 10 .4 11 .5 11 .1 10 .7 10 .9 10 .9 NT-HEMOL 9.0 NT-HEMOL 10.4 8.8 9.5 10.9 9.5 9.0 9.0 11 .6 11 .1 11 .4 11 .1 10 .7 11 .2 11 .0 11 .1 11 .4 11 .4 10.3 9.2 9.5 NT-HEMOL 8.3 10.2 8.4 9.2 8.5 11.0 NA mmol /L 142 .4 145 .0 144 .3 144 .9 144 .5 145 .0 144 .2 145 .6 144 .2 143 .6 144 .5 145 .7 143 .8 144 .9 143 .1 141 .6 143 .8 143 .7 145 .1 143 .2 K mmol/L RMV 6.47 RMV 5.65 5.92 6.19 6.95 6.52 6.14 6.11 6.09 5.43 5.78 RNV 6.06 6.89 6.26 6.08 5.90 5.30 790 Company Sanitized. Does not contain H-24516: Subchronic Toxicity 90-Day Gavage Study in Rats with One-Generation Reproductive Evaluations Animal Number SHEM SLIP SICT Individual Serum and Plasma Chemistry Values AST IU/L ALT IU/L SDH IU/L ALKP IU/L Male, Group: 0 mg/kg - Day 91 643143 NONE NONE NONE 87 643150 NONE NONE NONE 99 643185 NONE NONE NONE 110 643189 NONE NONE NONE 74 643204 NONE NONE NONE 86 643205 NONE NONE NONE 166 643235 NONE NONE NONE 80 643241 NONE NONE NONE 93 643288 NONE NONE NONE 66 643300 NONE NONE NONE 126 Male, Group: III - 25 mg/kg - Day 91 643173 SMALL NONE NONE 121 643179 TRACE NOME NONE 84 643180 NONE NOME NOME 62 643228 NONE NONE NONE 79 643240 NONE NONE NONE 93 " 643264 NONE NONE NONE 74 643272 SMALL NONE NONE 109 643290 NONE NONE NONE 95 643292 NONE NONE NONE 73 643308 NONE NONE NOME 82 33 20 .5 81 37 32 .2 131 55 35 .5 91 28 30 .6 103 34 26 .4 66 44 35 .8 84 30 28 .4 116 35 40 .6 116 31 22.4 71 36 13 .8 111 48 32 .6 90 42 23 .4 95 26 14 .1 76 22 21 .3 67 40 18 .7 93 28 22 .5 81 41 33 .6 109 38 18 .7 138 38 21 .2 104 40 27 .2 98 BILI mg/dL <0 .10 <0 .10 <0 .10 <0 .10 <0 .10 <0 .10 <0 .10 0 .12 <0 .10 0 .14 0 .11 <0 .10 <0 .10 <0 .10 <0 .10 0 .10 <0 .10 <0 .10 <0 .10 <0 .10 BUN mg/dL 16 15 13 14 14 13 19 15 18 17 14 14 14 16 16 12 19 19 14 14 791 .Company Sanitized. Does not contai .--.. H-24516: Subchronic Toxicity 90-Day Gavage Study in Rats with One-Generation Reproductive Evaluations Animal Number SHEM SLIP SICT Individual Serum and Plasma Chemistry Values AST IU/L ALT IU/L SDH IU/L ALKP IU/L Male, Group: V - 100 mg/kg - Day 91 643175 NSR NT NT NT 643224 NOME NONE NONE 64 643243 TRACE NONE NONE 71 643247 SMALL NONE NONE 80 643250 SMALL NONE NONE 104 643257 NONE NONE NONE 103 643275 SMALL NONE NONE 76 643311 SMALL NONE NONE 79 643314 NONE NONE NONE 63 643318 NONE NONE NONE 77 Male, Group: VII - 250 mg/kg - Day 91 643174 NONE NONE NONE 97 643193 NONE NONE NONE 85 643194 NONE NONE NONE 174 643201 NONE NONE NONE 98 643215 SMALL. NONE NONE 81 643252 NONE' NONE NONE 85 643259 NONE NONE NONE 110 643260 NONE NONE NONE 81 643298 NONE NONE NONE 71 643315 NONE NONE NONE 73 NT NT NT 29 16.5 161 37 28.8 174 30 18.8 125 32 13.9 112 44 26.7 129 30 26.6 136 37 29.8 154 26 21.9 135 31 27.2 126 26 16 .3 201 32 24 .1 183 92 28 .1 174 23 13 .7 162 31 25 .0 230 48 39 .2 166 71 41 .9 243 44 28 .3 192 33 19 .7 176 30 21 .6 135 BILI mg/dL NT <eO.10 0.10 0.10 0 .10 0.10 0.10 0.10 0.10 0.10 <:0 .10 <;0 .10 <:0 .10 :0 .10 <:0 .10 :0 .10 :0 .10 :0 .10 :0 .10 :0 .10 BUN mg/dL NT 15 17 15 16 18 13 17 15 14 13 15 17 17 17 15 15 16 14 15 792 Company Sanitized. Does not contain H-24516: Subchronic Toxicity 90-Day Gavage Study in Rats with One-Generation Reproductive Evaluations Animal Number FRIG me3/dL C3LUC me?/dL TP 9/ dL InclividLial Serum arid Pla sma 0 lemist ry Va].ues A LB 3/'dL GLiOB g/ dL CALC mg/ dL IP HS mg/ dL Male, Group: I - 0 mg/kg - I 3ay 91 643143 67 131 6 .5 3 .9 2 .6 10 .5 8 .6 643150 99 80 6 .1 4 .0 2 .1 10 .1 8 .1 643185 84 196 6 .8 4 .2 2 .6 11 .7 12 .0 643189 200 110 6 .8 4 .4 2 .4 10 .7 7 .4 643204 121 179 6 .9 4 .4 2 .5 11 .8 12 .9 643205 52 90 6 .7 4 .0 2 .7 10 .5 7 .8 643235 160 106 7 .4 4 .5 2 .9 11 .2 7 .5 643241 145 151 7 .6 4 .7 2 .9 12 .0 11 .7 643288 191 109 7 .0 4 .3 2 .7 10 .9 6 .9 643300 153 102 6 .8 4 .3 2 .5 10 .2 8 .6 Male, Group: III - 25 mg/kg - Day 91 643173 91 96 7 .3 4 .7 2 .6 10 .7 7 .4 643179 97 87 6 .2 4 .2 2 .0 9 .9 7 .9 643180 107 93 6 .7 4 .0 2 .7 10 .6 8 .6 643228 161 105 6 .6 4 .3 2 .3 10 .5 7 .9 643240 58 " 74 6 .7 4 .4 2 .3 10 .2 8 .0 643264 127 104 6 .8 4 .4 2 .4 10 .8 7 .8 643272 39 123 7 .1 4 .5 2 .6 11 .2 12 .4 643290 76 117 7 .2 4 .6 2 .6 10 .8 10 .0 643292 74 108 6 .7 4 .4 2 .3 10 .7 8 .5 643308 149 109 6 .7 4 .4 2 .3 10 .8 8 .2 NA rnmol /L 145 .2 147 .7 150 .8 146 .1 149 .3 147 .2 147 .1 149 .3 146 .5 143 .0 146 .2 147 .0 144 .1 144 .7 145 .2 147 .3 148 .5 145 .1 144 .9 145 .8 K mmo 1/L 6 .36 6 .89 7 .35 5 .54 6 .52 6 .10 6 .01 6 .88 5 .43 6 .25 6 .25 6 .08 6 .54 5 .85 5 .66 5 .38 6 .64 6 .07 6 .49 5 .69 793 Company Sanitized. Does not contain T H-24 516: Subchronic Toxicity 90-Day Gavage Study in Rats with One-Generation Reproductive Evaluations Animal Number TRIG mg/dL GLUC mg/dL TP g/dL Indlividual Se rum and Pliisma Chemist;ry Values ALB g/dL GLOB g/dL CALC mg/dL IPHS mg/dL Male, Group: V - 100 mg/kg - Day 91 643175 643224 643243 643247 643250 643257 643275 643311 643314 643318 NT NT NT NT NT NT NT 38 103 6.8 4.7 2.1 10.2 7.7 73 102 7.6 4.8 2.8 10.9 8.6 36 87 6.7 4.3 2.4 9.9 8.8 23 80 6.5 4.4 2.1 9.9 8.3 73 132 7.5 4.8 2.7 11.3 9.7 24 113 7.2 4.8 2.4 10.3 9.6 27 164 7.4 4.8 2.6 11.3 10.8 63 96 7.4 5.1 2.3 10.5 8.1 81 133 6.8 4.7 2.1 10.6 8.9 Male, Group: VII - 250 mg/kg - Day 91 643174 643193 643194 643201 643215 643252 643259 643260 643298 643315 98 116 8.1 5.6 2.5 11.1 8.7 37 89 7.8 5.5 2.3 10.7 8.2 20 143 7.4 5.1 2.3 10.4 9.4 75 93 7.7 5.4 2.3 10.9 7.9 3.9 95 7.5 5.3 2.2 10.5 8.0 10 138 7.6 5.3 2.3 11.5 10.6 34 162 8.3 6.0 2.3 11.9 12.2 19 149 7.3 5.1 2.2 11.0 9.8 36 90 7.8 5.3 2.5 11.0 7.9 22 83 7.0 4.9 2.1 10.3 8.0 NA mmol/L NT 147.5 147.4 143.9 144.5 146.4 148.0 145.3 146.8 144.8 144.9 146.2 140.6 145.5 145.0 145.0 148.2 144.1 146.6 145.7 K mmol/L NT 5.79 6.13 6.25 6.24 6.09 6.85 6.89 6.04 5.86 6.16 5.73 6.80 6.66 6.50 7.13 6.19 6.32 5.27 5.75 794 Company Sanitized. Does not contain T H-24516: Subchronic Toxicity 90-Day Gavage Study in Rats with One-Generation Reproductive Evaluations Animal Number FLIP PICT Individual Serum and Plasma Chemistry Values PFLU ug/mL SPEC Male, Group: I 0 mg/kg - Day 91 643143 NONE NONE 0. 643150 NONE NONE 0. 643185 NONE NONE 0. 643189 NONE NONE 0. 643204 NONE NONE 0. 643205 NONE NONE 0. 643235 NONE NONE 0. 643241 NONE NONE 0. 643286 NONE NONE 0. 643300 NONE NONE 0. ,e. Group; III - 25 mg/kg - Day 91 643173 NONE NONE 0. 643179 NONE NONE 0. 643180 NONE NONE 0. 643228 NONE NONE 0. 643240 NONE NONE 0. " 643264 NONE NONE 0. 643272 NONE NONE 0. 643290 NONE NONE 0. 643292 NONE NONE 0. 643308 NONE NONE 0. 795 Sanitized. Does not contain T Company H-24516: Subchronic Toxicity 90-Day Gavage Study in Rats with One-Generation Reproductive Evaluations Animal Number FLIP PICT Individual Serum and Plasma Chemistry Values PFLU ug/mL SPEC Male, Group: V - 100 ing/kg - Day 91 643175 NT NT N 643224 . NONE NONE 0. 643243 NONE NONE 0. 643247 NONE NONE 0. 643250 NONE NONE 0. 643257 NONE NONE 0. 643275 NONE NONE 0. 643311 NONE NONE 0. 643314 NONE NONE 0. 643318 NOME NONE 0. Male, Group: VII - 250 ing/kg - Day 91 643174 NONE NONE 0. 643193 NONE NONE 0. 643194 NONE NONE 0. 643201 NONE NONE 0. 643215 . NONE NONE 0. 643252 " NOME NONE 0. 643259 NONE NONE 0. 643260 NONE NONE 0. 643298 NONE NONE 0. 643315 NONE NONE 0. 796 Company Sanitized. Does not cont J& H-24516: Subchronic Toxicity 90-Day Gavage Study in Rats with One-Generation Reproductive Evaluations Animal Number SHEM SLIP SICT Individual Serum and Plasma Chemistry Values AST IU/L ALT IU/L SDH IU/L ALKP IU/L Male, Group: 0 mg/kg - Day 125 643162 NONE NONE NONE 84 43 11 .4 108 643172 NONE NONE NONE 68 28 16 .8 71 643195 NONE NONE NONE 78 39 21 .5 85 643226 TRACE NONE NONE 93 40 25 .3 48 643237 NONE NONE NONE 71 22 20 .1 73 643246 NONE NONE NONE 77 29 33 .7 68 643253 TRACE NONE NONE 78 30 17 .0 96 643262 TRACE NONE NONE 71 31 17 .1 85 643303 NONE NONE NONE 81 38 25 .1 101 643304 NOME NONE NONE 77 27 27 .3 72 .e. Group: VII - 250 mg/kg - Day 125 643151 NONE NONE NONE 62 27 12.0 92 643165 NONE NONE NONE 91 74 17.7 96 643220 TRACE NONE NONE 77 33 15.5 75 643225 SMALL NONE NONE 93 34 9.9 59 643234 NONE NONE NONE 70 36 10.5 60 643236 NONE " NONE NONE 76 31 13.5 71 643258 NONE NONE NONE 67 33 16.8 95 643266 NONE NONE NONE 34 29 9.3 75 643296 NONE NONE NONE 88 26 15.9 62 643316 NONE NONE NONE 78 41 18.5 81 BILI mg/dL <0 .10 <0 .10 <0 .10 0 .11 <0 .10 0 .10 <0 .10 <0 .10 <0 .10 <0 .10 <0.10 <0.10 <0.10 <0.10 <0.10 <0.10 <0.10 <0.10 <0.10 <0.10 BUN mg/dL 15 15 13 16 15 17 17 14 16 13 19 19 19 20 14 18 19 17 18 16 797 Company Sanitized. Does not co H-24516: Subchronic Toxicity 90-Day Gavage Study in Rats with One-Generation Reproductive Evaluations Animal Number TRIG mg/dL GLUC mg/dL TP g/dL Individual Se rum and Pic>sma Chemist;ry Values ALB g/dL GLOB g/dL CALC mg/dL IPHS mg/dL Male, Group: 1-0 mg/kg - Day 125 643162 41 92 6.9 4.2 2.7 10.4 7.4 643172 122 118 7.4 4.4 3.0 10.4 6.8 643195 124 103 6.6 4.4 2.2 10.2 6.7 643226 56 201 6.7 4.1 2.6 10.8 8.5 643237 64 113 6.5 4.2 2.3 10.7 7.9 643246 167 111 6.9 4.3 2.6 10.6 9.1 643253 91 102 7.3 4.4 2.9 10.7 7.8 643262 102 104 6.8 4.3 2.5 10.4 7.8 643303 . 98 180 7.5 4.6 2.9 11.2 11.6 643304 81 146 7.0 4.8 2.2 10.9 7.0 Male, Group: VII - 250 mg/kg - Day 125 643151 643165 643220 643225 643234 28 88 6.6 4.5 2.1 9.9 7.6 66 99 6.5 4.4 2.1 9.9 7.7 29 97 6.4 4.1 2.3 10.0 7.5 58 102 7.0 4.5 2.5 10.1 7.6 45 " 95 6.6 4.1 2.5 10.3 7.5 643236 57 106 7.2 4.3 2.9 10.4 7.4 643258 32 101 7.0 4.6 2.4 10.3 7.2 643266 43 119 6.4 3.9 2.5 9.9 8.3 643296 39 146 6.7 4.3 2.4 10.8 10.0 643316 154 107 7.0 4.7 2.3 10.2 7.4 NA mmol/L 146.2 146.4 146.5 146.2 146.6 148.1 146.3 145.3 146.9 145.3 146.9 147.3 149.7 145.5 146.5 146.4 146.1 143.7 146.8 146.9 K mmol/L 5.70 6.00 6.22 5.59 7.07 7.07 6.71 7.35 6.60 5.81 5.67 5.75 5.90 6.78 5.71 6.18 5.84 5.98 6.76 5.96 798 Sanitized. Does not coiniain Company H-24516: Subchronic Toxicity 90-Day Gavage Study in Rats with One-Generation Reproductive Evaluations Animal Number PLIP PICT PFLU ug/mL Individual Serum and Plasma Chemistry Values SPEC Male, Group: I 0 mg/kg - Day 125 643162 NONE NONE 0. 1 643172 TRACE NONE 0. 1 643195 NONE NONE 0. 1 643226 NONE NONE 0. 1 643237 NONE NONE 0. 1 643246 NONE NONE 0. 1 643253 NONE NONE 0. 1 643262 NT NT 0. 1 643303 HONE NONE 0. 1 643304 TRACE NONE 0. 1 Male, Group: VII - 250 mg/kg - Day 125 643151 TRACE NONE 0 .2 643165 NONE NONE 0 .2 643220 NONE NONE 0 .1 643225 NONE NONE 0 .1 643234 NONE. NONE QNS 643236 MT NT 0 .2 643258 NONE NONE 0 .1 643266 NONE NONE 0 .1 643296 NONE NONE 0 .1 643316 NONE NONE 0 .1 Accidental spillage of serum 799 Company Sanitized. Does not contain H-24516: Subchronic Toxicity 90-Day Gavage Study in Rats with One-Generation Reproductive Evaluations Animal Number SHEM SLIP Individual Serum and Plasma Chemistry Values SICT AST IU/L ALT IU/L SDH IU/L ALKP IU/L Female, Group: II - 0 mg/kg - Day 45 643354 NONE NONE NONE 95 643361 NONE NONE NONE 69 643362 NONE NONE NONE 99 643374 NONE NONE NONE 92 643398 NONE NONE NONE 84 643406 NONE NONE NONE 76 643436 NONE NONE NONE 73 643463 NONE NONE NONE 73 643477 NONE NONE NONE 101 643486 NONE NONE NONE 107 Female, Group: IV - 25 mg/kg - Day 45 643321 NSR NT NT NT 643324 NONE NONE NONE 60 643364 NONE NONE NONE 73 643380 TRACE NONE NONE 73 643389 NONE NONE NONE 106 643390 NONE" NONE NONE 73 643396 NONE NONE NONE 59 643410 NONE NONE NONE 93 643433 NONE NONE NONE 65 643458 SMALL NONE NONE 82 36 13 .9 98 28 15 .2 45 44 15 .1 80 45 26 .8 67 37 14 .7 64 39 18 .9 .56 33 14 .4 37 33 21 .1 60 46 28 .1 67 33 13 .6 81 NT NT NT 22 12 .8 86 42 13 .5 52 31 19 .3 61 23 20 .9 108 35 27 .4 98 32 20 .5 56 27 19 .6 46 37 17 .3 54 34 13 .7 74 BILI mg/dL 0 .10 0 .14 0 .14 0 .15 0 .12 0 .17 <0 .10 0 .13 0 .13 0 .17 NT 0 .15 <0 .10 0 .11 <0 .10 0 .13 0 .13 <0 .10 0 .15 0 .15 BUN mg/dL 16 14 16 18 15 17 15 15 20 17 NT 13 19 13 16 14 14 16 15 17 800 Company Sanitized. Does not contain T H-24516: Subchronic Toxicity 90-Day Gavage Study in Rats with One-Generation Reproductive Evaluations Animal Number SHEM SLIP Individual Serum and Plasma Chemistry Values SICT AST IU/L ALT IU/L SDH IU/L ALKP IU/L Female, Group: VI - 100 nig/kg - Day 45 643322 TRACE NONE NONE 91 643323 TRACE NONE NONE 66 643366 SMALL NONE NONE 72 643367 NOME NONE NONE 60 643392 NONE NONE NONE 77 643409 TRACE NONE NONE 105 643461 TRACE NONE NONE 66 643462 TRACE NONE NONE 58 643472 NONE NONE NONE 102 643489 NONE NONE NONE 73 iale. Group: VIII - 250 mg/kg - Day 45 643332 NONE NONE NONE 64 643340 TRACE NONE NONE 66 643341 TRACE NONE NONE 69 643359 TRACK NONE NONE 52 643370 TRACE NONE NONE 70 643404 TRA'CE NONE NOME 81 643408 NONE NONE NONE 63 643435 NONE NONE NOME 78 643446 TRACE NONE NONE 75 643466 NONE NONE NONE 72 29 14 .0 81 31 10 .5 93 28 13 .7 67 30 15 .1 58 37 16 .3 95 28 21 .9 114 24 13 .9 61 29 15 .5 80 40 . 20 .4 102 37 21 .6 78 29 14 .0 87 26 13 .0 73 48 19 .9 73 22 9 .4 87 35 19 .1 75 29 16 .4 71 27 14 .7 102 27 15 .1 61 23 25 .1 118 22 11 .2 61 BILI mg/dL 0. 13 0. 15 0. 13 0. 10 <0. 10 0. 12 0. 10 0. 17 <0. 10 <0. 10 <0 .10 0 .10 <0 .10 0 .12 <0 .10 0 .12 <0 .10 0 .14 0 .13 <0 .10 BUN mg/dL 16 15 12 16 19 19 13 17 14 16 15 15 15 16 19 16 17 13 14 17 801 Company Sanitized. Does not conta H-24516: Subchronic Toxicity 90-Day Gavage Study in Rats with One-Generation Reproductive Evaluations Animal Number TRIG mg/dL GLUC mg/dL rp g/'dL InclividLial Sei:um arid Pla sma Ctlemist ry Va]Lues A LB g/'dL GL OB 9/ dL CALC mg/ dL I P HS ing/ dL Female, Group: II - 0 cng/kg - Day 45 643354 41 104 7 .1 4 .5 2 .6 10 .5 6 .8 643361 82 98 7 .1 4 .9 2 .2 11 .1 7 .7 643362 42 101 6 .9 4 .5 2 .4 10 .7 6 .8 643374 43 92 7 .1 5 .0 2 .1 11 .4 7 .4 643398 78 97 6 .6 4 .7 1 .9 10 .7 8 .0 643406 63 84 7 .4 5 .1 2 .3 11 .0 7 .4 643436 95 94 7 .8 5 .5 2 .3 11 .0 7 .4 643463 107 117 8 .3 5 .9 2 .4 11 .8 8 .8 643477 41 98 7 .7 5 .5 2 .2 11 .1 8 .0 643486 35 87 6 .6 4 .5 2 .1 10 .6 6 .6 Female, Group: IV - 25 nig/kg - Day 45 643321 NT NT NT NT NT NT NT 643324 43 119 7 .6 5 .3 2 .3 11 .2 6 .7 643364 34 95 6 .9 4 .7 2 .2 11 .1 7 .5 643380 110 107 7 .6 5 .1 2 .5 11 .0 5 .8 643389 124 133 6 .7 4 .2 2 .5 11 .3 10 .0 643390 50 98 8 .1 5 .2 2 .9 11 .8 8 .1 643396 128 109 7 .7 5 .4 2 .3 12 .0 8 .6 643410 70 113 7 .4 5 .2 2 .2 11 .0 7 .3 643433 114 115 7 .4 5 .3 2 .1 11 .2 7 .4 643458 25 90 7 .0 4 .7 2 .3 10 .5 7 .1 iNA mmol /L 142 .8 143 .0 141 .3 145 .5 142 .2 142 .1 142 .1 146 .1 148 .5 141.4 NT 145 .7 144 .0 142 .8 148 .1 146 .0 142 .1 140 .0 141 .8 140 .8 mmo 1/ 5 .5 5 .7 5 .6 6 .1 5 .5 5 .7 5 .5 5 .5 5 .8 5 .3 N 5 .2 5 .9 5 .2 6 .5 5 .8 5 .9 5 .5 5 .4 5 .8 802 Company Sanitized. Does not contain H-24516: Subchronic Toxicity 90-Day Gavage Study in Rats with One-Generation Reproductive Evaluations Animal Number TRIG mg/dL GLUC mg/dL IP g/'AL Indi vidLial Senurn and Pla sma Ctlemist]ry Va].ues A:LB g/'dL GLOB g/dL CALC mg/idL IP:HS mg/ dL Female, Group.: VI - 1(30 mg/kg - Day 45 643322 643323 643366 643367 643392 643409 643461 643462 643472 643489 23 96 8 .2 5 .8 2.4 11 .4 8 .0 28 99 7 .5 5 .3 2.2 11 .1 7 .5 54 109 7 .4 5 .3 2.1 11 .0 7 .5 84 99 8 .2 5 .5 2.7 11 .9 7 .4 36 96 7 .8 5 .4 2.4 11 .4 8 .3 34 89 7 .1 4 .9 2.2 10 .6 8 .6 53 98 7 .7 5 .5 2.2 11 .3 7 .6 47 94 7 .6 5 .2 2.4 11 .4 7 .9 31 98 7 .7 5 .4 2.3 11 .2 9 .0 53 98 7 .6 5 .4 2.2 11 .1 7 .2 Female, Group: VIII - 250 ing/kg - Day 45 643332 643340 643341 643359 643370 643404 643408 643435 643446 643466 26 101 8 .4 5 .9 2.5 11 .8 7 .9 45 113 8 .1 5 .7 2.4 12 .0 7 .2 52 95 8 .1 5 .6 2.5 11 .8 8 .6 43 100 8 .2 5 .9 2.3 12 .0 8 .7 58. 96 8 .9 6 .0 2.9 12 .2 8 .0 -34 112 8 .3 5 .9 2.4 11 .7 7 .9 35 98 7 .9 5 .4 2.5 11 .4 7 .7 65 100 7 .5 5 .5 2.0 11 .2 7 .5 33 101 8 .6 6 .0 2.6 12 .1 7 .6 30 94 7 .5 5 .3 2.2 11 .1 7 .1 NA mmol /L 143 .5 141 .6 142 .4 142 .9 142 .8 143 .6 139 .8 141 .9 141 .0 145 .6 142 .6 142 .7 143 .4 142 .4 144 .1 142 .8 142 .8 142 .9 146 .7 142 .6 K mmo 1/L 5 .91 5 .40 6 .12 5 .91 6 .26 5 .77 5 .95 6 .17 5 .83 5 .45 5 .94 5 .88 6 .33 6 .05 6 .57 6 .41 6 .32 6 .32 6 .98 6 .42 803 Company Sanitized. Does not contain H-24516: Subchronic Toxicity 90-Day Gavage Study in Rats with One-Generation Reproductive Evaluations Animal Number SHEM SLIP Individual Serum and Plasma Chemistry Values SICT AST IU/L ALT IU/L SDH IU/L ALKP IU/L Female, Group: II - 0 ing/kg - Day 93 643354 NOME MOME NOME 106 643361 NONE SMALL NOME 76 643362 NONE NONE NOME 92 643374 NONE MONE MOME 160 643398 NOME NONE NOME 88 643406 NONE NOME MONE 72 643436 NONE SMALL MOME 67 643463 NONE MOME MOME 76 643477 NOME NONE MOME 77 643486 MOME NONE MOME 89 iale. Group: IV - 25 ing/kg - Day 93 643321 NSR NT NT MT 643324 NONE NONE NONE 67 643364 NONE NOME NONE 116 643380 NONE NOME NONE 71 643389 MQME. MOME NOME 86 643390 NOME NOME MONE 71 643396 NOME NONE MONE 60 643410 NOME NOME NOME 78 643433 MOME MOME MOME 75 643458 MOME MOME NONE 85 37 11.0 60 39 20.5 38 29 9.3 49 52 36.9 32 28 19.8 52 25 18.4 38 26 19.0 29 28 19.0 34 35 20.5 47 28 14.8 36 NT MT MT 26 18.0 52 40 8.3 28 28 17.3 36 46 16.5 65 32 20.7 47 34 17.8 25 29 20.3 27 27 13.4 44 32 15.1 72 BILI n>g/dL <0.10 0.11 0.11 0.22 0.12 0.16 <0.10 0.15 0.20 0.17 NT 0.10 <0.10 0.13 <0.10 <0.10 0.13 0.12 0.17 0.13 BU mg/dL 2 1 1 1 15 18 15 13 1 1 M 13 18 14 20 1 1 1 1 1 804 Company Sanitized. Does not co H-24516: Subchronic Toxicity 90-Day Gavage Study in Rats with One-Generation Reproductive Evaluations Animal Number SHEM SLIP SICT Individual Serum and Plasma Chemistry Values AST IU/L ALT IU/L SDH IU/L ALKP IU/L Female, Group: VI - 100 nig/kg Day 93 643322 MONE NONE NONE 99 643323 . TRACE NONE NONE 93 643366 SMALL NONE NONE 70 643367 NONE NOME NONE 91 643392 NONE NONE NONE 83 643409 NONE NONE NONE 90 643461 SMALL NONE NONE 100 643462 NONE NONE NONE 88 643472 NONE NONE NONE 100 643489 NONE NONE NONE 76 Female, Group: VIII 250 mg/kg - Day 93 643332 NONE NONE NONE 126 643340 NSR NT NT NT 643341 NONE NONE NONE 97 643359 NONE NONE NONE 59 643370 NONE NONE NONE 98 643404 NONE NONE NONE 82 643408 NONE NONE NONE 73 643435 NONE NONE NONE 84 643446 NONE NONE NONE 88 643466 NONE NONE NONE 77 28 10.2 63 34 20.9 62 28 13.3 40 41 17.5 34 30 23.3 72 31 16.0 58 36 23.3 40 34 18.4 44 35 21.3 75 36 18.5 64 57 21.7 76 NT NT NT 71 25.1 50 28 12.6 58 29 9.7 39 39 22.5 37 40 17.5 53 26 15.6 42 28 15.4 84 28 14.6 29 BILI mg/dL 0.14 <0.10 0.20 <0.10 <0.10 0.10 <0.10 0.10 0.11 0.10 <0.10 NT <0.10 0.13 0.14 0.14 <0.10 0.15 0.13 0.12 BU mg/d 1 1 1 1 1 2 1 1 1 1 1 N 1 1 1 1 1 1 1 1 805 Company Sanitized. Does not c H-24516: Subchronic Toxicity 90-Day Gavage Study in Rats with One-Generation Reproductive Evaluations Animal Number TRIG mg/dL GLUC mg/dL TP g/dL Individual SSerum and PI;isma Chemist:ry Values ALB g/dL GLOB g/dL CALC mg/dL IPHS mg/dL Female, Group: II - 0 ing/kg - Day 93 643354 61 84 7.1 4.5 2.6 10.5 6.4 643361 453 101 7.9 5.4 2.5 11.0 5.6 643362 92 92 6.7 4.5 2.2 10.6 6.1 643374 122 87 8.4 6.1 2.3 11.4 4.9 643398 63 99 6.9 4.7 2.2 10.4 6.1 643406 75 76 7.5 5.1 2.4 10.7 5.6 643436 363 96 7.8 5.4 2.4 10.9 6.3 643463 158 100 8.1 5.8 2.3 11.0 4.5 643477 113 89 7.5 5.6 1.9 10.9 5.3 643486 95 91 7.4 5.0 2.4 10.5 4.9 Female, Group: IV - 25 mg/kg - Day 93 643321 NT MT NT NT NT NT NT 643324 74 101 7.8 5.4 2.4 10.7 5.8 643364 52 92 7.6 5.2 2.4 10.9 5.8 643380 166 99 7.9 5.5 2.4 11.0 6.0 643389 .52 91 7.6 4.9 2.7 10.5 6.7 643390 76 96 8.2 5.6 2.6 11.4 5.7 643396 151 96 8.7 6.3 2.4 12.0 6.4 643410 64 105 7.8 5.6 2.2 11.0 5.0 643433 110 101 7.5 5.2 2.3 10.7 6.5 643458 42 95 7.4 5.0 2.4 10.5 5.9 HA mmol/L 142.8 140.9 143.2 143.1 146.1 142.8 143.4 144.4 146.0 144.0 MT 143.6 142.4 141.2 141.2 146.0 143.0 143.8 141.3 143.1 K mmol/L 5.76 4.68 5.33 5.06 5.29 5.59 5.32 4.93 5.84 5.14 NT 5.21 5.75 5.18 5.48 5.63 5.15 5.01 5.22 5.02 806 Company Sanitized. Does not cont H-24516: Subchronic Toxicity 90-Day Gavage Study in Rats with One-Generation Reproductive Evaluations Animal Number TRIG nig/dL GLUC mg/dL TP g/dL Inclividual Se:rum and Picisma Chemist;ry Values ALB g/dL GLOB g/dL CALC mg/dL IPHS mg/dL Female, Group: VI - 100 mg/kg - Day 93 643322 41 84 8.3 6.0' 2.3 11.3 6.4 643323 29 129 8.4 6.0 2.4 12.0 9.5 643366 74 108 8.1 6.0 2.1 11.4 5.4 643367 100 87 8.3 5.8 2.5 11.2 5.2 643392 32 98 8.7 6.1 2.6 11.4 6.8 643409 37 93 7.5 5.4 2.1 10.6 5.8 643461 40 128 8.5 5.9 2.6 11.6 8.4 643462 49 84 8.0 5.9 2.1 11.2 6.8 643472 44 84 9.1 6.5 2.6 11.4 6.7 643489 81 101 8.3 5.9 2.4 11.1 6.1 Female, Group: VIII - 250 mg/kg - Day 93 643332 56 97 8.8 6.2 2.6 11.6 6.8 643340 NT NT NT NT NT NT NT 643341 61 98 8.7 6.0 2.7 11.4 6.2 643359 69 92 8.5 6.0 2.5 12.0 7.2 643370 88. 99 9.1 6.1 3.0 11.9 7.7 643404 27 97 8.9 6.2 2.7 11.7 6.5 643408 57 90 7.9 , 5.4 2.5 10.9 6.4 643435 26 85 8.6 6.3 2.3 11.6 7.3 643446 28 93 8.3 6.0 2.3 11.3 5.6 643466 72 91 8.7 6.2 2.5 11.4 5.6 NA mmol/L 141.4 147.0 143.7 142.0 145.5 142.2 147.6 142.8 145.3 143.3 144 .1 NT 142.0 144.4 141.6 145.0 144.1 143.2 141.9 142.3 K mmol/L 5.35 5.54 5.74 5.16 6.17 5.06 6.22 5.92 5.61 5.41 5.86 NT 5.86 6.22 5.95 5.87 5.91 6.95 5.53 6.27 807 Company Sanitized. Does not contain H-24516; Subchronic Toxicity 90-Day Gavage Study in Rats with One-Generation Reproductive Evaluations Animal Number FLIP PICT PFLU ug/mL Individual Serum and Plasma Chemistry Values SPEC Female, Group: 643354 643361 643362 643374 643398 643406 643436 643463 643477 643486 II - 0 NONE NONE NONE NONE NONE NONE NONE NONE NONE NONE mg/kg - Day 93 NONE NONE NONE NONE NONE NONE NONE NONE NONE NONE Female, Group: IV - 25 mg/kg - Day 93 643321 643324 643364 643380 643389 643390 643396 643410 643433 643458 NT NONE NONE NONE NONE NOME" NONE NONE NONE NONE NT NONE NONE NONE NONE NONE NONE NONE NONE NONE 0 .1 0 .1 0 .1 0 .1 0 .1 0 .3 0 .1 0 .2 0 .1 0 .1 NSR 0.2 0.2 0.2 0.4 0.2 0.2 0.2 0.2 0.2 808 Company Sanitized. Does not cont H-24516: Subchronic Toxicity 90-Day Gavage Study in Rats with One-Generation Reproductive Evaluations Animal Number FLIP PICT PFLU lig/mL Individual Serum and Plasma Chemistry Values SPEC Female, Group: VI - 100 mg/kg - Day 93 643322 NONE NOME 0 .5 643323 NONE NONE 0 .3 643366 NONE NONE 0 .4 643367 NONE NONE 0 .5 643392 NONE NONE 0 .4 643409 NONE NONE 0 .2 643461 NONE NONE 0 .4 643462 NONE NONE 0 .4 643472 NONE NONE 0 .4 643489 NONE NONE 0 .2 lale. Group: VIII - 250 mg/kg - 643332 643340 643341 643359 643370 643404 643408 643435 643446 643466 NONE NT NONE NONE NONE NONE NONE NONE NONE NONE NONE NT NONE NONE NOME TRACE NOME NOME NOME NONE Day 93 1 .1 NSR 1 .0 0 .6 1 .0 0 .6 0 .7 1 .0 0 .6 0 .6 809 Company Sanitized. Does not contain T H-24516: Subchronic Toxicity 90-Day Gavage Study in Rats with One-Generation Reproductive Evaluations Animal Number SHEM SLIP SICT In.dividual Se rum and Picisma Chemist ry Values AST IU/L ALT IU/L SDH IU/L ALKP IU/L Female, Group: 11-0 m9/k9 - Day 125 643330 NONE NONE NONE 90 42 16.9 24 643336 NSR NT NT NT NT NT NT 643377 NONE NONE NONE 132 83 25.8 21 643387 NONE NONE NONE 74 26 14.0 31 643405 NONE NONE NONE 223 129 49.6 46 643415 NONE NONE NONE 224 126 39.0 .18 643425 TRACE NONE NONE 138 72 31.6 58 643426 NONE NONE NONE 80 31 18.7 35 643448 NONE NONE NONE 87 46 19.4 33 643453 NONE NONE NONE 70 34 17.6 34 Female, Group: VIII - 250 mg/kg - Day 125 643345 NONE NONE NONE 75 31 15.1 28 643347 NONE NONE NONE 72 40 16.9 43 643351 NONE NONE NONE 84 25 17.2 41 643358 NONE NONE NONE 95 48 17.4 32 643423 NOME. NONE NONE 131 42 16.9 72 643441 NONE TRACE NONE 81 34 18.1 39 643444 NONE NONE NONE 712 264 103.2 36 643456 NONE NONE NONE 70 29 14.4 24 643474 NONE NONE NONE 119 48 12.0 40 643481 NONE NONE NONE 82 60 18.4 24 BILI mg/dL 0.16 NT 0.14 <0.10 0.12 <0.10 <0.10 0.14 0.12 0.11 <0.10 0.11 <0.l0 0.10 0.12 0.11 0.24 <0.10 <0.10 <0.10 BUN mg/dL 17 NT 12 18 17 13 17 13 21 16 15 17 16 18 17 15 16 12 19 18 810 Company Sanitized. Does not conta H-24516: Subchronic Toxicity 90-Day Gavage Study in Rats with One-Generation Reproductive Evaluations Animal Number TRIG mg/dL GLUC mg/dL TP g/dL Individual Se rum and Pieisma Chemist;ry Values ALB g/dL GLOB g/dL CALC mg/dL IPHS mg/dL Female, Group: II - 0 ing/kg - Day 125 643330 643336 85 116 8.9 6.0 2.9 11.3 6.3 NT NT NT NT NT NT NT 643377 127 92 8.8 6.1 2.7 11.4 4.8 643387 81 103 8.1 5.5 2.6 10.9 5.2 643405 219 155 8.1 5.6 2.5 11.9 7.8 643415 271 92 8.8 5.8 3.0 11.3 5..0 643425 58 108 7.5 5.3 2.2 10.3 4.9 643426 162 99 8.1 5.7 2.4 11.0 5.6 643448 71 97 7.5 5.5 2.0 10.5 5.9 643453 148 99 8.1 5.5 2.6 11.0 5.9 Female, Group: VIII - 250 nig/kg - Day 125 643345 36 99 7.7 5.3 2.4 10.6 6.0 643347 46 94 8.5 5.6 2.9 10.8 5.3 643351 71 117 7.4 5.2 2.2 10.9 7.4 643358 248 100 8.8 6.1 2.7 11.3 7.5 643423 37. 110 8.2 5.2 3.0 10.9 8.1 643441 306 135 7.8 5.4 2.4 10.7 5.7 643444 74 97 8.7 5.6 3.1 11.3 5.8 643456 56 85 8.1 5.3 2.8 10.5 6.2 643474 34 99 8.2 5.6 2.6 10.6 6.1 643481 114 106 8.5 5.8 2.7 11.4 5.6 NA mmol/L 145.1 NT 145.8 144.8 147.5 146.0 146.5 145.7 145.2 142.7 145.3 146.6 144.1 142.4 143.4 145.0 142.6 142.6 140.8 145.8 K mmol/L 5.17 NT 4.90 5.86 5.86 4.98 5.59 4.78 4.91 5.70 5.36 5.51 6.10 5.38 4.76 4.85 5.92 5.28 5.18 6.11 811 Company Sanitized. Does not contai H-24516: Subchronic Toxicity 90-Day Gavage Study in Rats with One-Generation Reproductive Evaluations Animal Number FLIP PICT Individual Serum and Plasma Chemistry Value PFLU ug/mL SPEC Female, Group: II - 0 mg/kg - Day 125 643330 NONE NONE 0 .1 643336 NT NT NT 643377 NONE NONE 0 .1 643387 NONE NONE 0 .1 643405 NONE NONE 0 .1 643415 TRACE NONE 0 .1 643425 NONE NONE 0 .1 643426 NONE NONE 0 .1 643448 NONE NONE 0 .1 643453 TRACE NONE 0 .1 Female, Group: VIII 250 mg/kg - Day 125 643345 NONE NOME 0. 643347 NONE NONE 0. 643351 NONE NOME 0. 643358 TRACE NONE 0. 643423 NONE NONE 0. 643441 NONE NONE 0. 643444 -NONE NONE 0. 643456 NONE NONE 0. 643474 NONE NONE 0. 643481 NONE NONE 0. 812 ^^^'''"-''-"o.c.n  H-24516: Subchronic Toxicity 90-Day Gavage Study in Rats with One-Generation Reproductive Evaluations Animal Number QUAL COL CLAR Male, Group: 643143 643150 643185 643189 643204 643205 643235 643241 643288 643300 1-0 ing/kg LIGHT LIGHT LIGHT LIGHT LIGHT MEDIUM LIGHT LIGHT LIGHT LIGHT - Day 44 YELLOW YELLOW YELLOW YELLOW YELLOW YELLOW YELLOW YELLOW YELLOW YELLOW HAZY CLEAR HAZY HAZY CLOUDY CLOUDY CLOUDY HAZY HAZY HAZY Male, Group: III - 25 mg/kg - Day 44 643173 643179 643180 643228 643240 643264 643272 643290 643292 643308 LIGHT LIGHT LIGHT LIGHT LIGHT. LIGHT LIGHT MEDIUM LIGHT LIGHT YELLOW YELLOW YELLOW YELLOW YELLOW YELLOW YELLOW YELLOW YELLOW YELLOW HAZY CLOUDY HAZY HAZY CLEAR HAZY CLEAR , CLOUDY CLOUDY CLOUDY Ind:Ividual Urineilysis Values; VOL UOSM SG pH mL mOsm/kg UGLU mg/dL KET mg/dL 10.4 3.9 6.9 8.6 10.8 3.6 12.4 21.4 4.4 3.2 16.8 4.6 19.0 7.0 4.6 14.2 5.8 11.0 5.6 11.0 782 1373 1179 1363 1083 1631 967 526 1519 1404 547 1724 684 1003 1625 618 1689 844 659 799 1.024 1.043 1.036 1.042 1.031 1.052 1.029 1.017 1.047 1.044 1.018 1.053 1.021 1.033 1.049 1.020 1.051 1.027 1.021 1.026 7.0 NEGATIVE 15 7.0 NEGATIVE NEGATIVE 6.5 NEGATIVE 5 7.5 NEGATIVE 15 7.5 NEGATIVE 5 6.5 NEGATIVE 5 8.0 NEGATIVE NEGATIVE 8.0 NEGATIVE 5 6.5 NEGATIVE 5 7.5 NEGATIVE 15 7.5 NEGATIVE 5 6.5 NEGATIVE 15 8.5 NEGATIVE 5 6.5 NEGATIVE 5 7.0 NEGATIVE 15 7.0 NEGATIVE 5 6.5 NEGATIVE 5 7.5 NEGATIVE 5 8.5 NEGATIVE 15 7.5 NEGATIVE 5 813 ca^ SWb.d. Doe. ,,,, ^  H-24516: Subchronic Toxicity 90-Day Gavage Study in Rats with One-Qeneration Reproductive Evaluations Animal Number QUAL COL CLAR Male, Group: V - 100 mg/kg - Day 44 643175 643224 643243 643247 643250 643257 643275 643311 643314 643318 LIGHT LIGHT MEDIUM MEDIUM MEDIUM LIGHT LIGHT MEDIUM LIGHT LIGHT YELLOW YELLOW YELLOW YELLOW YELLOW YELLOW YELLOW YELLOW YELLOW YELLOW HAZY HAZY HAZY HAZY HAZY CLEAR CLOUDY HAZY CLOUDY HAZY Male, Group: VII - 250 mg/kg - Day 44 643174 643193 643194 643201 643215 643252 643259 643260 643298 643315 LIGHT MEDIUM LIGHT LIGHT LIGHT LIGHT LIGHT LIGHT LIGHT LIGHT YELLOW YELLOW YELLOW YELLOW YELLOW YELLOW YELLOW YELLOW YELLOW YELLOW CLOUDY HAZY HAZY CLEAR HAZY CLEAR HAZY HAZY CLEAR CLEAR . Individual Urineilysis Valueti VOL UOSM SG PH mL mOsm/kg UGLU mg/dL KET mg/dL 17.8 3.3 3.3 4.0 3.9 4.8 13.4 6.0 16.2 7.4 5.5 3.2 9.6 5.6 23.5 7.8 25.0 11.8 59.0 20.4 611 1924 QMS 2334 1663 1394 820 1352 591 1305 1219 2502 848 1609 419 838 505 743 217 475 1.020 1.058 1.075 1.068 1.051 1.044 1.025 1.043 1.019 1.042 1.039 1.068 1.026 1.050 1.014 1.027 1.016 1.024 1.007 1.016 7.0 NEGATIVE 15 6.5 NEGATIVE 5 6.5 NEGATIVE 5 6.5 NEGATIVE 5 7.0 NEGATIVE 15 6.5 NEGATIVE 5 8.5 NEGATIVE 15 7.0 NEGATIVE 15 7.5 NEGATIVE 5 7.0 NEGATIVE 5 7.5 NEGATIVE 5 7.0 NEGATIVE 5 8.0 NEGATIVE 5 6.5 NEGATIVE 5 8.5 NEGATIVE NEGATIVE 7.0 NEGATIVE 5 8.5 NEGATIVE 5 7.0 NEGATIVE 5 8.0 NEGATIVE NEGATIVE 7.0 NEGATIVE 5 814 CompanySanded. Does notc H-24516: Subchronic Toxicity 90-Day Gavage Study in Rats with One-Generation Reproductive Evaluations Animal Number URO EU/dL UMTP mg/dL SPEC Individual Urinalysis Values Male, Group: 0 ing/kg Day 44 643143 0 .2 45 643150 0 .2 84 643185 0 .2 75 643189 0 .2 149 643204 0 .2 51 643205 0 .2 119 643235 0 .2 78 643241 0 .2 20 643288 0 .2 57 643300 0 .2 93 Male, Group: III 25 mg/kg - Day 44 643173 643179 643180 643228 643240 643264 643272 643290 643292 643308 0.2 19 1.0 175 0.2 24 0.2 50 0.2 . 61 0.3. 21 0.2 104 0.2 50 0.2 58 0.2 63 FECAL CONTAMINATION OBSERVED FECAL CONTAMINATION OBSERVED FECAL CONTAMINATION OBSERVED FECAL FECAL FECAL FECAL CONTAMINATION CONTAMINATION CONTAMINATION CONTAMINATION OBSERVED OBSERVED OBSERVED OBSERVED 815 Company Sanitized. Does not cont H-24516: Subchronic Tpxicity 90-Day Gavage Study in Rats with One-Generation Reproductive Evaluations Animal Number URO EU/dL UMTP m9/dL SPEC Male, Group: V - 100 nig/kg - Day 44 643175 0.2 24 643224 0.2 163 643243 0.2 144 643247 0.2 152 643250 0.2 142 643257 0.2 151 643275 0.2 47 643311 0.2 81 643314 0.2 59 643318 0.2 63 Male, Group: VIZ - 250 nig/kg - Day 44 643174 0.2 81 643193 0.2 198 643194 0.2 51 643201 0.2 133 643215 0.2 16 643252 0.2 45 643259 0.2 22 643260 0.2 73 643298 0.2 10 643315 0.2 26 Individual Urinalysis Values 816 Company Sanitized. Does not contain H-24516: Subchronic Toxicity 90-Day Gavage Study in Rats with One-Generation Reproductive Evaluations Animal Number QUAL COL CLAR Male, Group: 643143 643150 643185 643189 643204 643205 643235 643241 643288 643300 1-0 ing/kg MEDIUM MEDIUM MEDIUM MEDIUM LIGHT MEDIUM MEDIUM LIGHT MEDIUM MEDIUM - Day 91 YELLOW YELLOW YELLOW YELLOW YELLOW YELLOW YELLOW YELLOW YELLOW YELLOW CLOUDY CLEAR CLEAR HAZY HAZY CLEAR HAZY CLOUDY CLEAR CLEAR Male, Group: 643173 643179 643180 643228 643240 643264 643272 643290 643292 643308 III - 25 MEDIUM MEDIUM LIGHT MEDIUM MEDIUM LIGHT" MEDIUM MEDIUM MEDIUM MEDIUM mg/kg - Day YELLOW YELLOW YELLOW BROWN YELLOW YELLOW YELLOW YELLOW YELLOW YELLOW 91 HAZY HAZY CLEAR CLOUDY CLEAR HAZY CLOUDY HAZY HAZY CLOUDY Indi vidual Urihalysis Values3 VOL UOSM SG pH mL mOsm/kg UGLU mg/dL KET mg/dL 3.5 1.4 9.0 10.0 6.4 5.4 12.0 19.0 1.8 2.2 RNV 12.0 8.3 4.2 5.7 26.0 13.0 6.6 10.0 4.5 2200 UTD 1440 1289 1077 1367 1322 614 UTD UTD 1.064 1.076 1.044 1.040 1.035 1.045 1.044 1.022 >1.083 1.065 1134 744 851 1924 1366 560 784 1154 1119 1947 1.035 1.028 1.026 1.059 1.041 1.020 1.024 1.036 1.033 1.058 7.0 NEGATIVE 15 6.5 NEGATIVE NEGATIVE 7.0 NEGATIVE NEGATIVE 7.5 NEGATIVE 15 7.0 NEGATIVE 5 6.5 NEGATIVE NEGATIVE 6.5 NEGATIVE NEGATIVE 6.0 NEGATIVE NEGATIVE 6.5 NEGATIVE 5 6.5 NEGATIVE 5 7.0 NEGATIVE 15 6.0 NEGATIVE 5 7.0 NEGATIVE 15 6.5 NEGATIVE 15 7.0 NEGATIVE 15 6.5 NEGATIVE NEGATIVE 6.5 NEGATIVE NEGATIVE 7.0 NEGATIVE NEGATIVE 8.5 NEGATIVE 15 7.0 NEGATIVE 15 817 Company Sanitized. Does not contain H-24516: Subchronic Toxicity 90-Day Gavage Study in Rats with One-Generation Reproductive Evaluations Animal Number QUAL COL CLAR Male, Group: V - 100 ing/kg - Day 91 643175 643224 643243 643247 643250 643257 643275 643311 643314 643318 NT MEDIUM MEDIUM LIGHT MEDIUM MEDIUM MEDIUM LIGHT LIGHT MEDIUM NT YELLOW YELLOW YELLOW YELLOW YELLOW YELLOW YELLOW YELLOW YELLOW NT HAZY HAZY HAZY CLOUDY CLEAR CLOUDY CLEAR HAZY HAZY Male, Group: VII - 250 nig/kg - Day 91 643174 643193 643194 643201 643215 643252 643259 643260 643298 643315 LIGHT MEDIUM MEDIUM MEDIUM MEDIUM MEDIUM- LIGHT LIGHT LIGHT MEDIUM YELLOW YELLOW YELLOW YELLOW YELLOW YELLOW YELLOW YELLOW YELLOW YELLOW HAZY CLEAR CLOUDY CLEAR CLEAR CLEAR CLOUDY HAZY CLOUDY CLEAR Ind:Lvidual Urineilysis Values! VOL UOSM SG pH mL mOsm/kg UGLU mg/dL KET mg/dL NSR 4.2 5.4 23.0 3.3 6.7 7.7 7.5 28.0 4.0 18.0 8.6 12.0 8.0 14.0 12.0 27.0 18.0 27.0 9.2 NT 1666 1948 642 2020 1414 1167 1088 376 1510 535 1181 892 1221 717 909 540 452 443 1037 NT 1.049 1.058 1.021 1.061 1.043 1.036 1.035 1.014 1.047 1.020 1.037 1.031 1.039 1.024 1.029 1.019 1.015 1.017 1.034 NT NT NT 7.0 NEGATIVE 5 7.0 NEGATIVE 5 6.0 NEGATIVE NEGATIVE 7.0 NEGATIVE 15 7.0 NEGATIVE NEGATIVE 7.5 NEGATIVE 5 7.5 NEGATIVE 5 6.0 NEGATIVE NEGATIVE 8.5 NEGATIVE 15 6.5 NEGATIVE NEGATIVE 7.5 NEGATIVE 5 6.0 NEGATIVE NEGATIVE 7.0 NEGATIVE 5 6.0 NEGATIVE NEGATIVE 6.0 NEGATIVE NEGATIVE 6.5 NEGATIVE NEGATIVE 7.0 NEGATIVE NEGATIVE 6.5 NEGATIVE NEGATIVE 7.0 NEGATIVE 5 818 Company Sanitized. Does not contain T H-24516: Subchronic Toxicity 90-Day Gavage Study in Rats with One-Generation Reproductive Evaluations Animal Number URO EU/dL UFLU "g UMTP mg/dL Male, Group: I - 0 nig/kg - Day 91 643143 0 .2 15 .9 147 643150 0 .2 QNS 149 643185 0 .2 28 .7 74 643189 0 .2 22 .6 102 643204 0 .2 15 .1 76 643205 0 .2 16 .0 86 643235 0 .2 25 .1 74 643241 0 .2 18 .0 25 643288 0 .2 QNS 177 643300 0 .2 QNS 276 Male, Group: III 25 mg/kg - Day 91 643173 0 .2 QMS 51 643179 0 .2 185.6 34 643180 0 .2 263.3 40 643228 1 .0 197.0 184 643240 0 .2 . 173.8 49 643264 0 .2 251.4 15 643272 0 .2 197.9 23 643290 0 .2 192.0 113 643292 0 .2 267.7 81 643308 0 .2 188.2 187 Individual Urinalysis Values SPEC Sample Status: URINALYSIS TO BE RUN MANUALLY - LOW VOLUM Sample status: PARTIAL VOLUME / ACCIDIDENTAL SPILLAGE 819 Company Sanitized. Does not contai H-24516: Subchronic Toxicity 90-Day Gavage Study in Rats with One-Generation Reproductive Evaluations Animal Number URO EU/dL UFLU ug UMTP mg/dL Male, Group: V - 100 mg/kg - Day 91 643175 NT NSR NT 643224 0.2 379.3 95 643243 0.2 761.9 151 643247 0.2 988.9 23 643250 0.2 710.4 168 643257 0.2 839.7 115 643275 0.2 540.2 64 643311 0.2 587.6 63 643314 0.2 676.5 32 643318 0.2 480.0 104 Male, Group: VII - 250 mg/kg - Day 91 643174 0.2 1911.3 24 643193 0.2 1537.7 56 643194 0.2 1378.9 63 643201 0.2 1093.7 71 643215 0.2 1259.4 27 643252 0:2" 1595.8 30 643259 0.2 1947.2 17 643260 0.2 992.5 21 643298 0.2 1592.1 35 643315 0.2 1427.1 56 Individual Urinalysis Values SPEC FECAL CONTAMINATION OBSERVED 820 Company Sanitized. Does not contai H-24516: Subchronic Toxicity 90-Day Gavage Study in Rats with One-Generation Reproductive Evaluations Animal Number QUAL COL CLAR Male, Group: 643162 643172 643195 643226 643237 643246 643253 643262 643303 643304 1-0 nig/kg LIGHT LIGHT LIGHT LIGHT MEDIUM MEDIUM MEDIUM LIGHT LIGHT LIGHT - Day 125 YELLOW YELLOW YELLOW YELLOW YELLOW YELLOW YELLOW YELLOW YELLOW YELLOW CLOUDY CLEAR CLEAR CLEAR HAZY HAZY HAZY CLEAR HAZY CLEAR Male, Group: VII - 250 mg/kg - Day 125 643151 643165 643220 643225 643234 643236 643258 643266 643296 643316 LIGHT MEDIUM MEDIUM MEDIUM MEDIUM LIGHT" MEDIUM LIGHT LIGHT MEDIUM YELLOW YELLOW YELLOW YELLOW YELLOW YELLOW YELLOW YELLOW YELLOW YELLOW CLEAR CLEAR HAZY HAZY HAZY HAZY HAZY HAZY CLEAR HAZY Ind:i-vidual Urineilysia Valuesi VOL UOSM SG pH mL mOsm/kg UGLU mg/dL KET mg/dL 13.4 8.7 17.8 14.2 10.4 5.9 7.9 11.8 6.7 23.2 6.5 3.5 4.2 2.0 4.1 13.4 3.2 21.0 11.2 3.1 803 984 501 744 853 1450 1391 1033 1357 404 1048 1971 1714 3194 2244 723 2743 642 744 2569 1.026 1.031 1.017 1.025 1.027 1.046 1.043 1.034 1.043 1.014 1.034 1.059 1.051 1.082 1.064 1.025 1.074 1.021 1.025 1.073 7.0 NEGATIVE 15 7.0 NEGATIVE 5 6.5 NEGATIVE NEGATIVE 6.0 NEGATIVE 5 7.0 NEGATIVE NEGATIVE 7.5 NEGATIVE 5 7'.0 NEGATIVE 5 6.5 NEGATIVE 15 7.0 NEGATIVE 15 6.0 NEGATIVE NEGATIVE 7.0 NEGATIVE 5 7.0 NEGATIVE 15 7.5 NEGATIVE 5 6.5 NEGATIVE 15 7.0 NEGATIVE 15 6.0 NEGATIVE NEGATIVE 6.5 NEGATIVE 15 6.0 NEGATIVE NEGATIVE 6.0 NEGATIVE 5 6.5 NEGATIVE 15 821 Company Sanitized. Does not contain H-24516: Subchronic Toxicity 90-Day Gavage Study in Rats with One-Generation Reproductive Evaluations Animal Number URO EU/dL UFLU ug UMTP mg/dL Male, Group: I 0 mg/kg - Day 125 643162 0 .2 11.,9 74 643172 0 .2 10.,3 45 643195 0 .2 16..0 41 643226 0 .2 16..9 29 643237 0 .2 12,.6 30 643246 0 .2 10,.0 116 643253 0 .2 15..7 88 643262 0 .2 18..3 52 643303 0 .2 15,.0 176 643304 0 .2 15,.7 13 Male, Group: VII 250 mg/kg - Day 125 643151 0.,2 76. 9 41 643165 0..2 55..0 134 643220 0,.2 96..0 86 643225 0,.2 78,.1 234 643234 0..2. 103..7 121 643236 0" .2 109..1 57 643258 0,.2 85..7 197 643266 0,.2 131..3 73 643296 0..2 71..2 44 643316 0..2 66..6 220 Individual Urinalysis Values SPEC FECAL CONTAMINATION OBSERVED FECAL CONTAMINATION OBSERVED 822 Company Sanitized. Does not H-24516: Subchronic Tpxicity 90-Day Gavage Study in Rats with One-Generation Reproductive Evaluations Animal Number UPLU "9 Male Group: 0 mg/kg - Day 181 643145 643210 643232 643265 643268 9.7 9.8 20.7 9.5 10.7 Male Group: 643202 643293 643305 643306 643310 III 25 mg/kg - 21.4 25.0 26.7 18.6 22.4 Day 1B1 Male Group: V 100 mg/kg - Day 181 643159 643169 643181 643206 643286 52.2 34.7. 41."0 21.9 45.6 Male Group: VII 250 mg/kg - Day 181 643149 643152 643178 643283 643295 64.4 64.2 71.0 79.9 66.0 Individual Urinalysis Values 823 Company Sanitized. Does not con H-24516: Subchronic Toxicity 90-Day Gavage Study in Rats with One-Generation Reproductive Evaluations Animal Number QUAL COL CLAR Female, Group: II - 0 643354 643361 643362 643374 643398 643406 643436 643463 643477 643486 LIGHT LIGHT MEDIUM LIGHT NT LIGHT LIGHT LIGHT LIGHT LIGHT mg/kg - Day YELLOW YELLOW YELLOW YELLOW NT YELLOW YELLOW YELLOW YELLOW YELLOW 45 CLOUDY CLEAR HAZY CLOUDY NT HAZY CLOUDY CLOUDY HAZY CLEAR Female, Group: IV - 25 mg/kg - Day 45 643321 643324 643364 643380 643389 643390 643396 643410 643433 643458 MT LIGHT LIGHT LIGHT LIGHT LIGHT LIGHT LIGHT LIGHT LIGHT MT YELLOW YELLOW YELLOW YELLOW YELLOW YELLOW YELLOW YELLOW YELLOW NT HAZY CLEAR HAZY CLEAR HAZY HAZY CLEAR HAZY CLEAR Indi-vidual Urinalysis Valuesi VOL UOSM SG pH mL mOsm/kg UGLU mg/dL KET mg/dL 9.0 11.2 1.3 5.4 QNS 12.0 6.2 2.8 1.0 2.9 NSR 10.0 3.2 12.0 3.6 5.0 9.8 7.5 1.6 9.2 583 705 3203 779 MT 578 681 2172 QNS 1468 NT 782 847 802 1461 1085 650 915 2888 620 1.018 1.022 1.068 1.023 NT 1.017 1.022 1.062 >1.083 1.044 NT 1.024 1.026 1.024 1.044 1.034 1.020 1.028 1.074 1.019 8.5 NEGATIVE NEGATIVE 7.0 NEGATIVE NEGATIVE 6.0 NEGATIVE NEGATIVE 7.0 NEGATIVE NEGATIVE NT NT NT 7.5 NEGATIVE NEGATIVE 8.0 NEGATIVE NEGATIVE 7.0 NEGATIVE NEGATIVE 6.0 NEGATIVE NEGATIVE 6.5 NEGATIVE NEGATIVE NT NT NT 7.0 NEGATIVE NEGATIVE 7.0 NEGATIVE NEGATIVE 7.0 NEGATIVE NEGATIVE 6.5 NEGATIVE NEGATIVE 7.0 NEGATIVE NEGATIVE 7.5 NEGATIVE NEGATIVE 7.0 NEGATIVE NEGATIVE 6.5 NEGATIVE 5 7.0 NEGATIVE NEGATIVE 824 Company Sanitized. Does not con H-24516: Subchronic Toxicity 90-Day Gavage Study in Rats with One-Generation Reproductive Evaluations Animal Number QUAL COL CLAR Female, Group: VI - 1130 mg/kg - Day 45 643322 643323 643366 643367 643392 643409 643461 643462 643472 643489 LIGHT LIGHT LIGHT LIGHT LIGHT LIGHT LIGHT LIGHT LIGHT LIGHT YELLOW YELLOW YELLOW YELLOW YELLOW YELLOW YELLOW YELLOW YELLOW YELLOW HAZY HAZY HAZY HAZY CLEAR CLEAR CLEAR HAZY CLEAR HAZY Female, Group: 643332 643340 643341 643359 643370 643404 643408 643435 643446 643466 VIII - LIGHT LIGHT LIGHT LIGHT LIGHT LIGHT LIGHT LIGHT LIGHT LIGHT 250 mg/kg - YELLOW YELLOW YELLOW YELLOW YELLOW YELLOW YELLOW YELLOW YELLOW YELLOW Day 45 HAZY HAZY HAZY HAZY HAZY CLEAR CLEAR CLOUDY HAZY CLEAR Individual Urineilysi.s Value;3 V OL UOSM SG P lmL mOsm/kg UGLU mg/dL KET mg/dL 12 .0 12 .4 11 .2 8 .8 4 .0 2 .1 5 .6 7 .8 6 .2 11 .4 16 .0 17 .0 20 .4 11 .2 6 .4 15 .6 12 .2 8 .2 7 .0 12 .2 482 470 633 843 1036 1265 907 840 775 608 414 471 377 680 1011 427 507 683 760 555 1 .015 1 .015 1 .019 1 .025 1 .031 1 .038 1 .027 1 .025 l .024 1 .019 l .013 l .015 1 .012 1 .021 1 .030 1 .014 l .016 1 .021 1 .023 l .017 7. 0 NEGATIVE NEGATIVE 7. 0 NEGATIVE NEGATIVE 7. 5 NEGATIVE NEGATIVE 7. 5 NEGATIVE NEGATIVE 7. 0 NEGATIVE NEGATIVE 6. 5 NEGATIVE NEGATIVE 8. 5 NEGATIVE NEGATIVE 6. 5 NEGATIVE NEGATIVE 7. 0 NEGATIVE NEGATIVE 7. 5 NEGATIVE NEGATIVE 7. 5 NEGATIVE NEGATIVE 7. 5 NEGATIVE NEGATIVE 7. 5 NEGATIVE NEGATIVE 8. 0 NEGATIVE NEGATIVE 7. 5 NEGATIVE NEGATIVE 7. 5 NEGATIVE NEGATIVE 7. 5 NEGATIVE NEGATIVE 8. 5 NEGATIVE NEGATIVE 8. 0 NEGATIVE NEGATIVE 7. 0 NEGATIVE NEGATIVE 825 Company Sanitized. Does not co H-24516: Subchronic Toxicity 90-Day Gavage Study in Rats with One-Generation Reproductive Evaluations Animal Number URO EU/dL UMTP mg/dL SPEC Individual Urinalysis Values Female, Group: 643354 643361 643362 643374 643398 643406 643436 643463 643477 643486 II - 0 0 .2 0 .2 0 .2 0 .2 NT 0 .2 0 .2 0 .2 0 .2 0 .2 mg/kg - Day 45 24 12 72 12 QNS 12 29 88 94 25 Female, Group: IV - 25 mg/kg - Day 45 643321 K NT 643324 0. 14 643364 0. 16 643380 0. 15 643389 0. 30 643390 0: 21 643396 0. 13 643410 0. 16 643433 0. 80 643458 0. 9 FECAL CONTAMINATION OBSERVED Sample Status: URINALYSIS TO BE RUN MANUALLY - LOW VOLUME FECAL CONTAMINATION OBSERVED FECAL CONTAMINATION OBSERVED Sample status: URINALYSIS TO BE RUN MANUALLY - LOW VOLUME FECAL CONTAMINATION OBSERVED 826 Company Sanitized. Does not co H-24516: Subchronic Toxicity 90-Day Gavage Study in Rats with One-Generation Reproductive Evaluations Animal Number URO EU/dL UMTP mg/dL SPEC Individual Urinalysis Values Female, Group: VI - 100 nig/kg - Day 45 643322 0. 643323 0. 643366 0. 643367 0. 643392 0. 643409 0. 643461 0. 643462 0. 643472 0. 643489 0. 13 12 FECAL CONTAMINATION OBSERVED 12 18 20 26 24 22 17 11 lale. Group: VIII 643332 0. 643340 0. 643341 0. 643359 0. 643370 0. 643404 0: 643408 0. 643435 0. 643446 0. 643466 0. 250 nig/kg - Day 45 14 11 9 41 37 11 28 20 FECAL CONTAMINATION OBSERVED 26 17 827 Company Sanitized. Does not H-24516: Subchronic Toxicity 90-Day Gavage Study in Rats with One-Generation Reproductive Evaluations Animal Number QUAL COL CLAR Female, Group: 11-0 643354 643361 643362 643374 643398 643406 643436 643463 643477 643486 LIGHT DARK MEDIUM DARK NT NT MEDIUM DARK DARK NT mg/kg - Day YELLOW YELLOW YELLOW YELLOW NT NT YELLOW YELLOW YELLOW NT 93 CLOUDY CLOUDY CLEAR HAZY NT NT HAZY HAZY HAZY NT Female, Group: IV - 25 1119/kg - Day 93 643321 643324 643364 643380 643389 643390 643396 643410 643433 643458 NT LIGHT MEDIUM MEDIUM MEDIUM " MEDIUM MEDIUM NT MEDIUM DARK NT YELLOW YELLOW YELLOW YELLOW YELLOW YELLOW NT YELLOW YELLOW NT HAZY HAZY HAZY CLEAR CLEAR CLEAR NT HAZY CLEAR IndjLvidual Urinalysis Valuesi VOL UOSM SG PH mL mOsm/kg UGLU mg/dL KET mg/dL 9.4 771 1.023 4.8 1080 1.034 3.0 1684 1.049 0.6 NT QNS QNS MT NT QNS NT NT 1.5 UTD 1.071 0.9 UTD >1.083 1.5 QNS >1.083 QNS NT NT NSR NT NT 6.6 1030 1.029 5.4 1096 1.034 8.6 760 1.023 2.2 1722 1.051 3.0 1610 1.049 4.0 1368 1.043 QNS NT NT 7.5 843 1.026 1.6 UTD 1.081 7.5 NEGATIVE NEGATIVE 8.0 NEGATIVE NEGATIVE 6.0 NEGATIVE NEGATIVE 6.0 NEGATIVE NEGATIVE NT NT NT NT NT NT 6.0 NEGATIVE NEGATIVE 6.5 NEGATIVE TRACE 5.5 NEGATIVE 5 NT NT NT NT NT NT 7.0 NEGATIVE NEGATIVE 6.0 NEGATIVE NEGATIVE 7.5 NEGATIVE NEGATIVE 5.5 NEGATIVE NEGATIVE 6.0 NEGATIVE NEGATIVE 6.0 NEGATIVE NEGATIVE NT NT NT 7.0 NEGATIVE NEGATIVE 6.5 NEGATIVE 5 828 Company Sanitized. Does not H-24516: Subchronic Toxicity 90-Day Gavage Study in Rats with One-Qeneration Reproductive Evaluations Animal Number QUAL COL CLAR Female, Group : VI - 100 mg/k9 - Day 93 643322 643323 643366 643367 643392 643409 643461 643462 643472 643489 DARK MEDIUM LIGHT MEDIUM MEDIUM DARK DARK DARK MEDIUM MEDIUM YELLOW YELLOW YELLOW YELLOW YELLOW YELLOW YELLOW YELLOW YELLOW YELLOW CLEAR CLEAR HAZY CLEAR CLEAR CLOUDY HAZY CLEAR CLEAR CLEAR Female, Group : VIII - 643332 643340 643341 643359 643370 643404 643408 643435 643446 643466 LIGHT NT LIGHT MEDIUM LIGHT LIGHT MEDIUM LIGHT MEDIUM MEDIUM 250 mg/k9 - YELLOW MT YELLOW YELLOW YELLOW YELLOW YELLOW YELLOW YELLOW YELLOW Day 93 HAZY NT CLEAR HAZY CLEAR HAZY CLEAR CLEAR CLEAR CLEAR Indi vidual Urin;llysiLS Value;3 VOL UOSM SG pH mL mOsm/kg UGLU mg/dL KET mg/dL 1.8 8.3 9.4 1.5 2.0 2.5 2.6 3.4 1.7 7.0 12.4 NSR 7.9 24.0 23.4 3.5 6.3 5.3 6.5 7.0 UTD 759 579 2411 1513 2065 1715 1750 2013 1067 539 NT 815 429 403 812 1033 816 1216 812 1 .068 1 .025 1 .019 1 .066 1 .047 1 -059 1 .054 1 .053 1 .057 1 -031 1 .019 NT 1 .024 1 .015 1 .013 1 .026 1 .030 1 .026 1 .039 1 .024 6.0 NEGATIVE NEGATIVE 6.0 NEGATIVE NEGATIVE 6.5 NEGATIVE NEGATIVE 6.0 NEGATIVE NEGATIVE 7.0 NEGATIVE NEGATIVE 6-5 NEGATIVE NEGATIVE 5.5 NEGATIVE 5 6.0 NEGATIVE NEGATIVE 6.0 NEGATIVE NEGATIVE 6.5 NEGATIVE NEGATIVE 6.0 NEGATIVE NEGATIVE NT NT NT 7.0 NEGATIVE NEGATIVE 5.5 NEGATIVE NEGATIVE 5.0 NEGATIVE NEGATIVE 6.0 NEGATIVE NEGATIVE 7.0 NEGATIVE NEGATIVE 5.5 NEGATIVE NEGATIVE 7.0 NEGATIVE NEGATIVE 6.5 NEGATIVE NEGATIVE 829 Company Sanitized. Does not H-24516: Subchronic Toxicity 90-Day Gavage Study in Rats with One-Generation Reproductive Evaluations Animal Number URO EU/dL UFLU TO UMTP mg/dL Female, Group: II - 0 mg/kg - Day 93 643354 0 .2 14.0 19 643361 0 .2 19.4 61 643362 0 .2 QMS 30 643374 0 .2 QNS QNS 643398 NT QNS QNS 643406 NT QNS QNS 643436 0 .2 QNS 152 643463 0 .2 QNS 140 643477 0 .2 QNS 99 643486 QNS QNS iale. Group: IV - 25 mg/kg - Day 93 643321 NT NSR NT 643324 0 .2 100.5 14 643364 0 .2 107.9 26 643380 0 .2 52.2 25 643389 0 .2 QNS 38 643390 " 0,2 84.2 41 643396 0 .2 99.7 145 643410 NT QNS QNS 643433 0.2 150.5 25 643458 0 .2 QNS 75 Individual Urinalyais Values SPEC FECAL CONTAMINATION OBSERVED FECAL CONTAMINATION OBSERVED Sample Status: URINALYSIS TO BE RUN MANUALLY - LOW VOLUM Sample status; URINALYSIS TO BE RUN MANUALLY - LOW VOLUM FECAL CONTAMINATION OBSERVED FECAL CONTAMINATION OBSERVED FECAL CONTAMINATION OBSERVED FECAL CONTAMINATION OBSERVED 830 C'w"*--" <?'--'*-- n.. CompanySanitized. Doe H-24516: Subchronic Toxicity 90-Day Gavage Study in Rats with One-Generation Reproductive Evaluations Animal Number URO EU/dL UFLU P3 UMTP mg/dL Female, Group: VI - 100 mg/k9 - Day 93 643322 0 .2 QNS 92 643323 0 .2 513.2 16 643366 0 .2 349.2 13 643367 0 .2 QNS 80 643392 0 .2 QNS 48 643409 0 .2 QNS 90 643461 0 .2 QNS 79 643462 0 .2 363.9 75 643472 0 .2 QNS 52 643489 0 .2 615.0 20 Female, Group: VIII - 250 mg/kg - Day 93 643332 0 .2 711. 47 643340 NT NS NT 643341 0 .2 500. 21 643359 0 .2 1902. 57 643370 0 .2 2039. 50 643404 0 ..2 - 519. 48 643408 0 .2 679. 114 643435 0 .2 454. 29 643446 0 .2 931. 67 643466 0 .2 493. 54 Individual Urinalysis Values SPEC 831 Company Sanitized. Does not cont H-24516: Subchronic Toxicity 90-Day Gavage Study in Rats with One-Generation Reproductive Evaluations Animal Number QUAL COL CLAR Female, Group : II - 0 643330 643336 643377 643387 643405 643415 643425 643426 643448 643453 LIGHT NT LIGHT MEDIUM LIGHT MEDIUM LIGHT MEDIUM MEDIUM LIGHT mg/kg - Day YELLOW NT YELLOW YELLOW YELLOW YELLOW YELLOW YELLOW YELLOW YELLOW 125 CLEAR NT CLEAR CLEAR CLEAR CLEAR CLEAR CLEAR CLEAR CLEAR Female, Group : VIII - 250 mg/kg - 643345 643347 643351 643358 643423 643441 643444 643456 643474 643481 LIGHT LIGHT LIGHT NT LIGHT MEDIUM " NT LIGHT MEDIUM NT YELLOW YELLOW YELLOW NT YELLOW YELLOW NT YELLOW YELLOW NT Day 125 CLEAR CLEAR CLEAR NT CLEAR HAZY NT HAZY CLEAR NT Indi-vidual Urinalysis Values1 VOL UOSM SG pH mL mOsm/kg UGLU mg/dL KET mg/dL 2.8 NT 3.5 2.6 7.9 3.2 15.4 1.0 1.2 9.0 11.0 4.8 4.9 QNS 7.9 3.3 QNS 9.0 2.8 QNS 1123 NT 1073 1589 894 1094 389 QNS QNS 668 1.036 NT 1.035 1.049 1 .027 1.036 1.014 1.076 1.070 1.021 495 951 1042 QNS 594 1704 QNS 476 1617 QNS 1.018 1.029 1.033 NT 1.019 1.052 NT 1.017 1.048 NT 5.5 NEGATIVE NEGATIVE NT NT NT 5.5 NEGATIVE NEGATIVE 6.0 NEGATIVE NEGATIVE 6.5 NEGATIVE NEGATIVE 5.. 5 NEGATIVE NEGATIVE 5.5 NEGATIVE NEGATIVE 5.0 NEGATIVE NEGATIVE 6.0 NEGATIVE NEGATIVE 6.0 NEGATIVE NEGATIVE 5.0 NEGATIVE NEGATIVE 5.5 NEGATIVE NEGATIVE 6.0 NEGATIVE 5 NT NT NT 5.5 NEGATIVE NEGATIVE 6.5 NEGATIVE 5 NT NT NT 6.0 NEGATIVE NEGATIVE 6.0 NEGATIVE 5 NT NT NT 832 Company Sanitized. Does not cont H-24 516: Subchronic Toxicity 90-Day Gavage Study in Rats with One-Generation Reproductive Evaluations Animal Number URO EU/dL UFLU P9 UMTP nig/dL Female, Group: II - 0 nig/kg - Day 125 643330 0 .2 3 .6 81 643336 t TT ]NT MT 643377 0..2 5 .6 29 643387 0,.2 5 .5 57 643405 0,.2 11 .6 26 643415 0..2 6 .4 428 643425 0,,2 18 .4 7 643426 0,.2 Q]MS 185 643448 0 .2 Q'MS 80 643453 0 .2 8 .9 90 Female, Group: VIII 250 mg/kg - Day 125 643345 0 .2 30.3 12 643347 0 .2 30.0 100 643351 0 .2 49.7 25 643358 NT QNS QNS 643423 0 .2 40.0 23 643441 0.2 - 38.9 49 643444 NT QNS QNS 643456 0 .2 73.6 228 643474 0 .2 44.2 48 643481 NT QNS QNS Individual Urinalysis Values SPEC FECAL CONTAMINATION OBSERVED Sample status: Sample status: URINALYSIS TO BE RUN MANUALLY URINALYSIS TO BE RUN MANUALLY LOW VOLUME LOW VOLUME 833 Company Sanitized. Does not cont H-24516: Subchronic Toxicity 90-Day Gavage Study in Rats with One-Generation Reproductive Evaluations Animal Number UPLU P9 Female, Group: 643383 643384 643402 643465 643484 II - 0 m9/kg - 12.7 8.6 6.1 12.3 4.1 Day 181 Female, Group: IV - 25 mg/kg - Day 181 643379 643391 643411 643437 643483 12.9 11.1 NT 23.8 QNS Female, Group: VI - 100 mg/kg - Day 181 643360 643373 643381 643382 643412 24.6 23.1 18 .-2 23.1 11.0 Female, Group: VI 11 250 mg/kg - Day 181 643329 643356 643388 643450 643487 17.2 28.7 QNS 47.7 23.6 Individual Urinalysis Values 834 Company Sanitized. Does not con H-24516: Subchronic Tpxicity 90-Day Gavage Study in Rats with One-Generation Reproductive Evaluations Animal Number EPIT UWBC URBC Indivi<iual Urine Mic:roscopic Vcilues NCRY MICR SPER SPEC Male, Group: 1-0 mg/k9 - Day 44 643143 NONE 0 0 FEW MANY 3 643150 NONE 0 0 FEW MODERATE 2 643185 NONE 0 0 FEW MODERATE 1 643189 NONE 0 0 FEW MODERATE 2 643204 NONE 1-10 1-10 MODERATE MANY 0 643205 PEW 0 0 FEW MANY 1 643235 NOME 0 1-10 PEW MANY 1 643241 NONE 0 0 FEW MODERATE 0 643288 FEW 0 0 FEW MANY 3 643300 NONE 0 0 MANY MANY 0 Male, Group: III - 25 mg/kg - Day 44 643173 NONE 0 0 MODERATE MODERATE 2 643179 FEW 0 0 FEW MANY 1 643180 FEW 0 0 FEW MANY 2 643228 NONE 0 >50 NONE MODERATE 2 643240 NONE. 0 0 FEW MODERATE 1 643264 NOME 0 0 FEW MODERATE 2 643272 NOME 0 0 FEW FEW 0 643290 NOME 0 0 MODERATE MANY 1 643292 NONE 0 0 NONE MANY 1 643308 NOME 0 0 MODERATE MANY 1 835 Company Sanitized. Does not con H-24516: Subchronic Toxicity 90-Day Gavage Study in Rats with One-Generation Reproductive Evaluations Animal Number EPIT UWBC URBC Indiviciual Urine Miciroscopic Vcilues NCRY MICR SPER SPEC Male, Group: V - 100 mg/k9 - Day 44 643175 643224 643243 643247 643250 643257 643275 643311 643314 643318 MONE NONE FEW NONE NONE NONE PEW NONE NONE NONE 0 0 0 0 1-10 0 0 0 0 0 0 0 0 1-10 0 0 0 0 0 0 Male, Group: VII - 250 mg/kg - Day 44 643174 643193 643194 643201 643215 643252 643259 643260 643298 643315 NONE NONE FEW NONE NONE NONE NONE FEW NONE FEW 0 1-10 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 1-10 NONE FEW FEW FEW NONE FEW FEW FEW FEW MODERATE FEW MODERATE FEW FEW MODERATE NONE FEW NONE FEW FEW MANY MODERATE FEW MODERATE FEW FEW MANY MANY MANY MODERATE MANY FEW MODERATE PEW MODERATE MODERATE MODERATE MANY MODERATE MODERATE 0 1 1 1 1 0 1 0 1 2 2 2 1 FEW COARSELY GRANULAR CAST 2 2 1 2 0 1 2 836 Company3an,feed. Does not c H-24516: Subchronic Toxicity 90-Day Gavage Study in Rats with One-Generation Reproductive Evaluations Animal Number EPIT UWBC URBC Individual Urine Microscopic Values NCRY MICR SPER SPEC Male, Group: I - 0 mg/kg - Day 91 643143 FEW 0 643150 NONE 0 643185 PEW 0 643189 FEW 0 643204 FEW 0 643205 NONE 0 643235 PEW 0 643241 NONE 0 643288 NONE 0 643300 PEW 0 .e, Group: 643173 643179 643180 643228 643240 643264 643272 643290 643292 643308 III - 25 mg/kg - Day 91 NONE NONE NONE PEW. NONE NONE NONE NONE NONE NONE 1-10 0 0 0 0 0 0 0 0 6 0 1-10 1-10 0 0 0 0 0 0 0 1-10 0 >50 0 0 0 0 0 0 FEW MODERATE FEW FEW FEW FEW FEW FEW FEW PEW FEW NONE NONE NONE FEW FEW FEW FEW FEW MODERATE FEW FEW MANY MODERATE FEW FEW FEW FEW FEW FEW NONE MANY FEW FEW PEW MODERATE MODERATE MODERATE MODERATE FEW Sample status: BELOW REC FEW COARSELY GRANULAR CAST Sample status: 1-MUCUS BELOW REC Sample Status: BELOW REC Sample status: Sample status: BELOW REC BELOW REC Sample status: Sample Status: BELOW REC BELOW REC Sample status: BELOW REC 837 Company Sanitized. Does n H-24516: Subchronic Toxicity 90-Day Gavage Study in Rats with One-Generation Reproductive Evaluations Animal Number EPIT UWBC URBC Individual'Urine Microscopic Values NCRY MICR SPER SPEC Male, Group: V - 100 mg/kg - Day 91 643175 NSR NT 643224 FEW 0 643243 NONE 0 643247 FEW 0 643250 FEW 0 643257 FEW 0 643275 MODERATE 0 643311 FEW 0 643314 NOME 0 643318 NONE 0 NT 1-10 0 0 0 1-10 0 0 0 0 Male, Group: VII 250 mg/kg - Day 91 643174 643193 643194 643201 643215 643252 643259 643260 643298 643315 FEW FEW FEW NONE NONE. NONE PEW NONE NONE NONE 0 0 0 0 0 0 0 1-10 0 0 0 0 0 0 0 0 0 0 0 0 NT NONE FEW PEW FEW FEW FEW FEW FEW FEW NONE NONE FEW FEW PEW FEW NONE FEW FEW MODERATE NT MANY MODERATE FEW MODERATE MANY MANY MODERATE MANY FEW MANY MANY FEW MODERATE FEW MODERATE MANY FEW MANY MODERATE NT 2 Sample status: BELOW REC 2 2 1 Sample status: BELOW REC 3 1-MUCUS 1 1 1 1 Sample status: BELOW REC 1-MUCUS 1-MUCUS 838 Company Sanitized. Does not con H-24516: Subchronic Toxicity 90-Day Gavage Study in Rats with One-generation Reproductive Evaluations Animal Number EPIT UWBC URBC Individual Urine Microscopic Values NCRY MICR SPER SPEC Male, Group: I - 0 nig/kg - Day 125 643162 FEW 1--10 0 643172 NONE 0 0 643195 FEW 0 0 643226 NONE 0 0 643237 FEW 0 0 643246 NONE 0 0 643253 FEW 0 0 643262 PEW 0 0 643303 FEW 1--10 0 643304 FEW 0 0 e. Group: 643151 643165 643220 643225 VII - 250 NONE FEW FEW NONE mg/kg - Day 0 1-10 0 0 125 0 0 1-10 0 643234 643236 643258 643266 643296 643316 " NONE FEW NONE NONE NONE NONE 0 1--10 1-10 0 0 0 1-10 1-10 0 0 0 0 NONE NONE NONE NONE NONE FEW FEW NONE. FEW NONE MODERATE FEW MODERATE FEW MODERATE MODERATE MODERATE FEW MODERATE FEW NONE FEW MODERATE FEW MODERATE NONE PEW NONE NONE FEW MODERATE MODERATE MODERATE MODERATE MODERATE FEW MODERATE FEW FEW MANY 3 2 3 3 1-MUCUS 3 1-MUCUS 3 1-MUCUS 2 3 3 1-MUCUS 3 3 3 Sample status BELOW RECO 0 Sample status BELOW RECO 3 Sample status BELOW RECO 2-MUCUS; FEW CCOARSELY GRAN 2 Sample status BELOW RECO 3 1-MUCUS; MODER ; NUMBER O 1 Sample status BELOW RECO 3 1-MUCUS 2 2 Sample status BELOW RECO 839 Company Sanitized. Does not contai H-24516: Subchronic Toxicity 90-Day Gavage Study in Rats with One-Generation Reproductive Evaluations Animal Number EPIT UWBC URBC Individual Urine Microscopic Values NCRY MICR SPER SPEC Female, Group: 643354 643361 643362 643374 643398 643406 643436 643463 643477 643486 II - 0 NONE FEW FEW FEW QNS FEW NONE FEW FEW FEW nig/kg - Day 45 0 0 1-10 0 NT 0 0 1-10 0 1-10 0 MODERATE MANY 0 NONE FEW 0 FEW FEW 0 NONE MODERATE NT NT NT 0 FEW MODERATE 0 MODERATE MANY 0 MODERATE FEW 0 NONE FEW 0 FEW FEW Female, Group: IV - 25 nig/kg - Day 45 643321 643324 643364 643380 643389 643390 643396 643410 643433 643458 NSR MONE NONE FEW FEW FEW FEW NONE PEW NONE NT 0 0 0 0 1-10 0 0 1-10 0 NT NT NT 0 FEW MODERATE 0 MODERATE MODERATE 0 FEW MODERATE 0 FEW FEW 0 NONE FEW 0 MODERATE MODERATE 0 FEW MODERATE 0 FEW FEW 0 MODERATE MANY 0 0 0 Sample status: BELOW RECO 0 NT 0 0 0 0 Sample status: BELOW RECO 0 Sample status: BELOW RECO NT 0 0 0 0 0 0 0 0 Sample status: BELOW RECO 0 840 Company Sanitized. Does not contai H-24516: Subchronic Toxicity 90-Day Gavage Study in Rats with One-Generation Reproductive Evaluations Animal Number EPIT UWBC URBC Individual Urine Microscopic Values NCRY MICR SPER SPEC Female, Group: VI - 100 nig/kg - Day 45 643322 FEW 0 0 643323 FEW 0 0 643366 FEW 0 0 643367 FEW 0 0 643392 NONE 0 0 643409 PEW 1-10 0 643461 NONE 0 0 643462 FEW 0 0 643472 NONE 0 0 643489 NONE 1-10 0 Female, Group: 643332 643340 643341 643359 643370 643404 643408 643435 643446 643466 VIII - 250 mg/kg - NONE NONE PEW FEW NONE NOME " NONE FEW NONE FEW 0 0 0 0 0 0 0 1-10 0 1-10 Day 45 0 0 0 0 0 0 0 0 0 0 FEW NONE FEW MODERATE NONE FEW MODERATE NONE FEW FEW MODERATE MODERATE FEW MODERATE FEW MODERATE FEW FEW MODERATE NONE MODERATE MANY MODERATE MODERATE FEW NONE MODERATE MANY FEW FEW MODERATE MODERATE MODERATE MANY MODERATE MODERATE MANY MODERATE MODERATE FEW Sample status: BELOW RECO 841 Company Sanitized. Does not co -24516: Subchronic Toxicity 90-Day Gavage Study in Rats with One-Generation Reproductive Evaluations Animal Number EPIT UWBC I JRBC Female, Group; 643354 643361 643362 643374 643398 643406 643436 643463 II - 0 FEW FEW FEW FEW QNS QNS NONE FEW r ng/kg - Day 93 0 0 0 0 NT NT 0 0 0 0 :L-10 0 NT NT 0 0 643477 FEW 0 0 643486 QNS NT NT Female, Group: IV - 25 nig/kg - Day 93 643321 NSR NT NT 643324 FEW 0 0 643364 FEW 0 0 643380 FEW 0 0 643389 NONE 0 0 643390 NONE 0 0 643396 FEW 0 0 643410 QNS NT NT 643433 FEW 0 0 643458 FEW 0 0 Indiviciual Urine Mic]roscopic V;ilues NCRY MICR SPER SPEC FEW . FEW NONE NONE NT NT NONE PEW MANY MANY MODERATE MANY NT NT MODERATE FEW NONE NT MODERATE NT NT FEW FEW FEW NONE NONE NONE NT FEW NONE NT FEW MODERATE MANY FEW MODERATE MODERATE NT MODERATE MODERATE 0 0 1-MUCUS 0 1-MUCUS 0 Sample status: BELOW RECO NT NT 0 Sample status: BELOW RECO 0 Sample status: BELOW RECO FEW COARSELY GRANULAR CASTS 0 Sample status: BELOW RECO NT NT 0 0 1-MUCUS 0 2-MUCUS 0 Sample status: BELOW RECO 0 Sample status: BELOW RECO 0 Sample status: BELOW RECO NT 0 1-MUCUS 0 Sample status: BELOW RECO 842 Company Sanitized. Does not con H-24516: Subchronic Toxicity 90-Day Gavage Study in Rats with One-Generation Reproductive Evaluations Animal Number EPIT UWBC URBC Female, Group: VI - 100 nig/kg - Day 93 643322 643323 643366 643367 643392 643409 643461 643462 643472 643489 FEW PEW FEW PEW FEW FEW FEW FEW PEW NONE 0 0 0 0 0 0 0 0 0 1-10 0 0 0 0 0 0 0 0 0 1-10 Female, Group: 643332 643340 643341 643359 643370 643404 643408 643435 643446 643466 VIII FEW NSR NONE PEW FEW FEW PEW FEW NONE FEW 'kg - Day 93 0 0 NT NT 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 Individual Urine Microscopic Values NCRY MICR SPER SPEC NONE NONE NONE NONE NONE NONE NONE FEW NONE NONE FEW MODERATE MODERATE MODERATE FEW MANY MODERATE MODERATE FEW MODERATE NONE NT NONE NONE NONE NONE NONE NONE NONE NONE FEW NT MODERATE MODERATE FEW FEW FEW MANY MODERATE MODERATE 0 Sample sCatus BELOW RECO 0 2 -MUCUS 0 1-MUCUS 0 Sample status BELOW RECO 0 Sample status BELOW RECO 0 Sample status BELOW RECO 0 Sample status BELOW RECO 0 Sample status BELOW RECO 0 Sample status BELOW RECO 0 1-MUCUS 0 1-MUCUS NT 0 2-MUCUS 0 1-MUCUS 0 1-MUCUS 0 1-MUCUS 0 0 1-MUCUS 0 0 1-MUCUS 843 Company Sanitized. Does not H-24516: Subchronic Toxicity 90-Day Gavage Study in Rats with One-Generation Reproductive Evaluations Animal Number EPIT UWBC URBC Female, Group: 11-0 mg/kg - Day 125 643330 FEW 1-10 0 643336 NSR NT NT 643377 FEW 1-10 0 643387 FEW 0 0 643405 FEW 1-10 0 643415 NONE 0 0 643425 NONE 0 0 643426 FEW 1-10 0 643448 FEW 1-10 0 643453 NONE 1-10 0 Female, Group: 643345 643347 643351 643358 643423 643441 643444 643456 643474 643481 VIII - FEW FEW PEW QNS FEW FEW QNS NONE FEW QNS 250 mg/kg - 0 1-10 1-10 NT 1-10 1-10 NT 0 1-10 NT Day 125 0 0 0 NT 0 0 NT 0 0 NT Individua 1 Urine Micsroscopic Vsalues NCRY MICR SPER SPEC FEW NT FEW FEW FEW FEW FEW FEW FEW FEW FEW FEW FEW NT FEW FEW NT FEW FEW NT FEW NT FEW FEW FEW FEW FEW FEW FEW FEW PEW FEW FEW NT FEW FEW NT FEW FEW NT 0 Sample status BELOW RECO NT 0 Sample status BELOW RECO 0 Sample status BELOW RECO 0 0 Sample status BELOW RECO 0 0 Sample status BELOW RECO 0 Sample status BELOW RECO 0 0 0 0 NT 0 0 Sample status: BELOW RECO NT 0 0 Sample status: BELOW RECO NT 844 Company Sanitized. Does not APPENDIX L INDIVIDUAL HEPATIC BETA-OXIDATION ACTIVITY 845 Company Sanitized. Does not contain TSCA CBI H-24516: Subchronic Toxicity 90-Day Gavage Study in Rats with One-Generation Reproduction Evaluations DuPont-5386 Individual Hepatic Beta-Oxidation Activity In Male Rats At The 10-Day Time Point Group I ffl V VH Animal Number 645904 645905 645906 645907 .645908 645909 645910 645911 645912 645913 645914 645915 645916 645917 645918 645919 645920 645921 645922 645923 Beta-Oxidation Rate (nmol/min/mg protein) 6.8 4.6 3.3 6.1 2.8 7.1 8.2 7.5 11.1 10.6 9.1 12.3 8.7 8.2 14.3 17.7 17.1 9.3 17.4 20.5 846 Company Sanitized. Does not contain TSCA CB1 H-24516: Subchronic Toxicity 90-Day Gavage Study in Rats with One-Generation Reproduction Evaluations DuPont-5386 Individual Hepatic Beta-Oxidation Activity In Male Rats At The 90-Day Time Point Group I ffl V VH Animal Number 643241 643300 643143 643205 643235 643173 643290 643272 643292 643228 643250 643243 643311 643318 643247 643194 643252 643260 643315 643215 Beta-Oxidation Rate (nmol/mm/mg protein) 6.0 5.8 2.9 6.4 4.6 15.7 9.1 6.7 16.2 17.2 20.8 20.9 18.4 20.9 22.5 32.2 35.7 54.5 51.6 48.5 847 Company Sanitized. Does not contain TSCA CBI H-24516: Subchronic Toxicity 90-Day Gavage Study in Rats with One-Generation Reproduction Evaluations DuPont-5386 Individual Hepatic Beta-Oxidation Activity In Male Rats At The 36-Day Recovery Time Point Animal Group____Number 643237 643226 643195 643246 643253 vn 643225 643296 643258 643316 643220 Beta-Oxidation Rate (nmol/mio/mg protein) 12.4 9.1 6.0 9.7 5.5 27.8 26.8 34.5 34.4 26.4 848 Company Sanitized. Does not contain TSCA CBl H-24516: Subchronic Toxicity 90-Day Gavage Study in Rats with One-Generation Reproduction Evaluations___________DuPont-5386 Individual Hepatic Beta-Oxidation Activity In Male Rats At The 92-Day Recovery Time Point Animal Group____Number I 643145 643210 643232 643265 643268 vn 643149 643152 643178 643283 643295 Beta-Oxidation Rate (nmol/min/mg protein) 8.7 10.0 7.9 8.6 6.4 32.5 15.8 25.7 25.0 26.7 849 Company Sanitized. Does not contain TSCA CBt H-24516: Subchronic Toxicity 90-Day Gavage Study in Rats with One-Generation Reproduction Evaluations DuPont-5386 Individual Hepatic Beta-Oxidation Activity In Female Rats At The 10-Day Time Point Group n IV VI Vffl Animal Number 645926 645927 645928 645929 645930 645931 645932 645933 645934 645935 645936 645937 645938 645939 645940 645941 645942 645943 645944 645945 Beta-Oxidation Rate (nmol/min/mg protein) 6.6 7.2 7.7 7.0 12.0 9.9 8.6 4.7 6.0 9.4 13.6 13.4 11.9 17.8 12.3 18.7 21.8 20.9 18.7 25.4 850 Company Sanitized. Does not contain TSCA CBl H-24516: Subchronic Toxicity 90-Day Gavage Study in Rats with One-Generation Reproduction Evaluations DuPont-5386 Individual Hepatic Beta-Oxidation Activity In Female Rats At The 90-Day Time Point Group n IV VI Vffl Animal Number 643477 643374 643406 643486 643361 Beta-Oxidation Rate (nmol/min/mg protein) 5.1 7.1 9.4 7.7 9.9 643390 643396 643380 643433 643389 7.4 12.3 9.0 17.2 15.5 643322 . 643489 643409 643366 643367 29.3 25.2 32.2 24.4 23.3 643341 643370 643446 643435 ' 643466 39.3 24.5 30.4 32.9 21.4 851 Company Sanitized. Does not contain TSCA CBI H-24516: Subchronic Toxicity 90-Day Gavage Study in Rats with One-Generation Reproduction Evaluations_______________DuPont-5386 Individual Hepatic Beta-Oxidation Activity In Female Rats At The 36-Day Recovery Time Point Animal Group____Number n 643405 643425 643448 643426 643415 Vffl 643347 643456 643423 643345 645551 Beta-Oxidation Rate (nmol/min/mg protein) 10.5 11.5 9.5 8.4 8.3 18.9 14.8 20.2 21.1 24.6 852 Company Sanitized. Does not contain TSCA CBI H-24516: Subchronic Toxicity 90-Day Gavage Study in Rats with One-Generation Reproduction Evaluations_______________DuPont-5386 Individual Hepatic Beta-Oxidation Activity In Female Rats At The 92-Day Recovery Time Point Animal Group____Number n 643383 643384 643402 643465 643484 vm 643329 643365 643388 643450 643487 Beta-Oxidation Rate (nmol/min/mg protein) 19.2 15.2 19.0 19.3 19.4 35.9 34.3 27.9 31.2 29.1 853 Company Sanitized. Does not contain TSCA CBl APPENDIX M INDIVIDUAL ANIMAL FINAL BODY AND ORGAN WEIGHTS 854 Company Sanitized. Does not contain TSCA CBI H-24516: Subchronic Toxicity 90-Day Gavage Study in Rats with One-Generation Reproduction Evaluations INDIVIDUAL ANIMAL FINAL BODY AND ORGAN WEIGHTS FOR MALE RATS DESIGNATED FOR 90-DAY EXPOSURE EVALUATION Group ; I ANIMAL - 0 ing/kg/day Sex : MALES FBW (Gms) BRAIN (Gms) %FBW ADRENAL GLANDS (Gms) %FBW %BRAIN 643143 643150 643185 643189 643204 643205 643235 643241 643288 643300 Mean S.D. 512.40 470.00 586.60 601.50 570.80 563.80 622.00 612.90 584.20 575.00 569.92 46.423 2.079 2.080 2.155 2.165 2.089 2.142 2.223 2.145 2.121 1.982 0.4057 0.4426 0.3674 0.3599 0.3660 0.3799 0.3574 0.3500 0.3631 0.3447 2.118 0.3737 0.065 0.0296 0.053 0.049 0.048 0.061 0.068 0.072 0.047 0.045 0.050 0.061 0.0103 0.0104 0.0082 0.0101 0.0119 0.0128 0.0076 0.0073 0.0086 0.0106 2.5493 2.3558 2.2274 2.8176 3.2551 3.3613 2.1143 2.0979 2.3574 3.0777 0.055 0.0098 2.6214 0.009 0.0018 0.4747 Group : III - 25 ANIMAL FBM (Gms) mg/kg/day Sex BRAIN (Gms) %FBW :MALES ADRENAL GLANDS (Gms) %FBW %BRAIN 6431-73 643179 643180 643228 643240 643264 643272 643290 643292 643308 Mean S.D. 504.40 516.40 543.80 677.90 485.90 628.90 518.20 548.90 526.70 611.20 556.23 62.229 2.042 2.086 2.110 2.319 2.147 2.312 2.123 1.986 2.278 2.210 0.4048 0.4040 0.3880 0.3421 0.4419 0.3676 0.4097 0.3618 0.4325 0.3616 2.161 0.3914 0.115 0.0328 0.064 0.059 0.058 0.065 0.056 0.064 0.072 0.049 0.044 0.070 0.0127 0.0114 0.0107 0.0096 0.0115 0.0102 0.0139 0.0089 0.0084 0.0115 3.1342 2.8284 2.7488 2.8029 2.6083 2.7682 3.3914 2.4673 1.9315 3.1674 0.060 0.0109 2.7848 0.009 0.0017 0.4083 EPIDIDYMIDES (Gms) %FBW %BRAIN 1.368 1.442 1.793 1.487 1.687 1.698 1.756 1.804 1.545 1.477 0.2670 0.3068 0.3057 0.2472 0.2956 0.3012 0.2823 0.2943 0.2645 0.2569 65.801 69.327 83.202 68.684 80.756 79.272 78.992 84.103 72.843 74.521 1.606 0.2821 75.750 0.160 0.0217 6.4413 EPIDIDYMIDES (Gma) %FBW %BRAIN 1.460 1.461 1.332 1.527 1.697 1.771 1.434 1.400 1.499 1.496 0.2895 0.2829 0.2449 0.2253 0.3492 0.2816 0.2767 0.2551 0.2846 0.2448 71.499 70.038 63.128 65.847 79.041 76.600 67.546 70.493 65.803 67.692 1.508 0.2735 69.769 0.133 0.0343 4.9518 (Gms) HEART %FBW %BRAIN 1.491 1.455 1.804 1.797 1.967 1.764 1.830 1.663 1.701 1.668 0.2910 0.3096 0.3075 0.2988 0.3446 0.3129 0.2942 0.2713 0.2912 0.2901 71.717 69.952 83.712 83.002 94.160 82.353 82.321 77.529 80.198 84.157 1.714 0.3011 80.910 0.155 0.0195 6.8226 (Gms) HEART %FBW %BRAIM 1.536 1.951 1.515 1.955 1.692 1.779 1.545 1.845 1.628 1.665 0.3045 0.3778 0.2786 0.2884 0.3482 0.2829 0.2981 0.3361 0.3091 0.2724 75.220 93.528 71.801 84.304 78.808 76.946 72.774 92.900 71.466 75.339 1.711 0.3096 79.309 0.165 0.0342 8.2378 (Gms) 3.529 3.684 4.020 4.200 3.443 4.429 4.172 3.804 3.667 3.765 3.871 0.321 (Gins) 3.920 3.892 4.435 4.830 3.761 4.623 3.627 3.968 4.474 4.077 4.161 0.402 PBW - Final Body Weight 855 Company Sanitized. Does not conta f. H-24516: Subchronic Toxicity 90-Day Gavage Study in Rats with One-Generation Reproduction Evaluations INDIVIDUAL ANIMAL FINAL BODY AND ORGAN WEIGHTS FOR MALE RATS DESIGNATED FOR 90-DAY EXPOSURE EVALUATION Group : V - 100 m9/k9/day Sex :MALES ANIMAL FBW (Gms) BRAIM (Gms) %FBW ADRENAL GLANDS (Gms) tFBW %BRAIN EPIDIDYMIDES (Gms) %FBW %BRAIH (Gms) HEART FBW %BRAIN 643224 643243 643247 643250 643257 643275 643311 643314 643318 Mean S.D. 478.10 533.20 544.30 470.60 499.60 532.90 506.70 498.60 567.00 514.56 31.860 2.080 2.065 2.054 1.991 2.076 1.948 1.999 2.191 2.239 0.4351 0.3873 0.3774 0.4231 0.4155 0.3655 0.3945 0.4394 0.3949 2.071 0.4036 0.093 0.0259 0.049 0.051 0.066 0.041 0.043 0.058 0.045 0.055 0.057 0.0102 0.0096 0.0121 0.0087 0.0086 0.0109 0.0089 0.0110 0.0101 2.3558 2.4697 3.2132 2.0593 2.0713 2.9774 2.2511 2.5103 2.5458 0.052 0.0100 2.4949 0.008 0.0012 0.3873 1.517 1.346 1.499 1.382 1.424 1.293 1.523 1.557 1.338 0.3173 0.2524 0.2754 0.2937 0.2850 0.2426 0.3006 0.3123 0.2360 72.933 65.182 72.980 69.412 68.593 66.376 76.188 71.063 59.759 1.431 0.2795 69.165 0.096 0.0300 4.9268 1.552 1.473 1.746 1.341 1.423 1.659 1.576 1.413 1.654 0.3246 0.2763 0.3208 0.2850 0.2848 0.3113 0.3110 0.2834 0.2917 74.615 71.332 85.005 67.353 68.545 85.164 78.839 64.491 73.872 1.537 0.2988 74.358 0.135 0.0182 7.4153 (Gms) 3.840 4.361 4.304 4.137 3.672 4.430 4.279 ' 4.203 4.463 4.188 0.268 Group : VII - 250 ANIMAL FBW (Gms) mg/kg/day Sex BRAIN (Gms) %FBW :MALES ADRENAL GLANDS (Gma) %FBW %BRAIN 643174 643193 643194 643201 643215 643252 643259 643260 643298 643315 Mean S.D. 566.60 527.80 510.80 546.00 510.50 498.60 490.10 441.10 516.10 474.80 508.24 35.490 2.046 2-178 2.069 2.170 2.000 2.193 2.080 1.930 2.175 2.139 0.3611 0.4127 0.4051 0.3974 0.3918 0.4398 0.4244 0.4375 0.4214 0.4505 2.098 0.4142 0.088 0.0266 0.059 0.055 0.051 0.050 0.057 0.052 0.049 0.040 0.065 0.067 0.0104 2.8837 0.0104 2.5253 0.0100 2.4650 0.0092-2.3041 0.0112 2.8500 0.0104 2.3712 0.0100 2.3558 0.0091 2.0725 0.0126 2.9885 0.0141 3.1323 0.055 0.0107 2.5948 0.008 0.0016 0.3462 EPIDIDYMIDES (Gms) %FBW %BRAIN 1.468 1.422 1.448 1.542 1.686 1.431 1.484 1.271 1.540 1.383 0.2591 0.2694 0.2835 0.2824 0.3303 0.2870 0.3028 0.2881 0.2984 0.2913 71.750 65.289 69.985 71.060 84.300 65.253 71.346 65.855 70.805 64.656 1.468 0.2892 70.030 0.110 0.0193 5.7887 (Gms) HEART %FBW %BRAIN 1.716 1.440 1.468 1.710 1.421 1.578 1.515 1.352 1.430 1.478 0.3029 0.2728 0.2874 0.3132 0.2784 0.3165 0.3091 0.3065 0.2771 0.3113 83.871 66.116 70.952 78.802 71.050 71.956 72.837 70.052 65.747 69.098 1.511 0.2975 72.048 0.122 0.0168 5.5358 (Gms) 5.024 4.847 4.156 4.806 5.102 4.572 4.824 3.841 5.006 4.082 4.626 0.445 FBW - Final Body Weight 856 Compaq sa^ed. Does not cont H-24516: Subchronic Toxicity 90-Day Gavage Study in Rats with One-Generation Reproduction Evaluations INDIVIDUAL ANIMAL FINAL BODY AND ORGAN WEIGHTS FOR MALE RATS DESIGNATED FOR 90-DAY EXPOSURE EVALUATION Group : I - 0 mg/kg/day Sex :MALES ANIMAL (Gms) LIVER tFBW BRAIN (Gms) SPLEEN %FBW 4BRAIN (Gms) TESTES %FBW tBRAIN (Gms) THYMUS %FBW %BRAIM 643143 643150 643185 643189 643204 643205 643235 643241 643288 643300 Mean S.D. 12.027 12.058 15.885 17.971 14.869 16.314 19.863 16.844 14.978 15.334 2.3472 2.5655 2.7080 2.9877 2.6049 2.8936 3.1934 2.7482 2.5638 2.6668 578.50 579.71 737.12 830.07 711.78 761.62 893.52 785.27 706.18 773.66 15.614 2.7279 735.74 2.409 0.2426 99.373 0.763 0.771 0.788 0.857 0.938 1.002 0.969 0.720 0.745 0.703 0.1489 0.1640 0.1343 0.1425 0.1643 0.1777 0.1558 0.1175 0.1275 0.1223 36.700 37.067 36.566 39.584 44.902 46.779 43.590 33.566 35.125 35.469 0.826 0.1455 38.935 0.109 0.0201 4.5784 3.281 3.861 3.654 3.693 3.704 3.624 4.302 3.675 3.307 3.187 0.6403 0.8215 0.6229 0.6140 0.6489 0.6428 0.6916 0.5996 0.5661 0.5543 157.82 185.63 169.56 170.58 177.31 169.19 193.52 171.33 155.92 160.80 3.629 0.6402 171.16 0.323 0.0754 11.887 0.505 0.390 0.508 0.597 0.352 0.277 0.594 0.512 0.539 0.206 0.0986 0.0830 0.0866 0.0993 0.0617 0.0491 0.0955 0.0835 0.0923 0.0358 24.291 18.750 23.573 27.575 16.850 12.932 26.721 23.869 25.413 10.394 0.448 0.0785 21.037 0.135 0.0221 5.9719 Group : III - 25 ANIMAL (Gms) ing/kg/day Sex LIVER " FBW BRAIM ;MALES (Gms) SPLEEN %FBW tBRAIN 643173 643179 643180 643228 643240 643264 643272 643290 643292 643308 Mean S.D. 14.493 15.519 16.875 20.448 13.780 19.596 15.966 17.459 15.715 18.920 2.8733 3.0052 3.1032 3.0164 2.8360 3.1159 3.0810 3.1807 2.9837 3.0955 709.75 743.96 799.76 881.76 641.83 847.58 752.05 879.10 689.86 856.11 16.877 3.0291 780.18 2.210 0.1093 85.088 0.510 0.685 0.569 0.779 0.712 1.071 0.769 0.820 0.525 0.900 0.1011 0.1326 0.1046 0.1149 0.1465 0.1703 0.1484 0.1494 0.0997 0.1473 24.976 32.838 26.967 33.592 33.163 46.324 36.222 41.289 23.047 40.724 0.734 0.1315 33.914 0.175 0.0248 7.5143 (Gms) TESTES %FBW %BRAIN 3.142 3.714 3.168 3.651 3.591 3.761 2.928 2.860 3.989 3.165 0.6229 0.7192 0.5826 0.5386 0.7390 0.5980 0.5650 0.5210 0.7574 0.5178 153.87 178.04 150.14 157.44 167.26 162.67 137.92 144.01 175.11 143.21 3.397 0.6162 156.97 0.389 0.0910 13.696 (Gms) THYMUS %FBW tBRAIN 0.233 0.443 0.307 0.514 0.448 0.281 0.391 0.453 0.251 0.408 0.0462 0.0858 0.0565 0.0758 0.0922 0.0447 0.0755 0.0825 0.0477 0.0668 11.410 21.237 14.550 22.165 20.866 12.154 18.417 22.810 11.018 18.462 0.373 0.0674 17.309 0.098 0.0176 4.6311 FBW - Final Body Weight 857 C'-P'nyS.n,,,,..,. oo.. no,^,^ H-24516: Subchronic Toxicity 90-Day Gavage Study in Rats with One-Generation Reproduction Evaluations INDIVIDUAL ANIMAL FINAL BODY AMD ORGAN WEIGHTS FOR MALE RATS DESIGNATED FOR 90-DAY EXPOSURE EVALUATION Group : V - 100 mg/kg/day Sex :MALES ANIMAL (Gins) LIVER tFBM tBRAIN (Gms) SPLEEN tFBW tBRAIN (Gms) TESTES %FBM %BRAIN (Gms) THYMUS tFBW tBRAIN 643224 643243 643247 643250 643257 643275 643311 643314 643318 18.368 23.501 23.174 17.434 19.589 22.561 22.345 20.904 21.877 3.8419 4.4075 4.2576 3.7046 3.9209 4.2336 4.4099 4.1925 3.8584 883.08 1138.1 1128.2 875.64 943.59 1158.2 1117.8 954.08 977.09 0.687 0.843 0.919 0.677 0.754 0.743 0.887 0.857 0.818 0.1437 0.1581 0.1688 0.1439 0.1509 0.1394 0.1751 0.1719 0.1443 33.029 40.823 44.742 34.003 36.320 38.142 44.372 39.115 36.534 3.605 3.331 3.793 3.386 3.497 3.526 3.499 3.653 3.693 0.7540 0.6247 0.6969 0.7195 0.7000 0.6617 0.6905 0.7327 0.6513 173.32 161.31 184.66 170.07 168.45 181.01 175.04 166.73 164.94 0.242 0.500 0.429 0.367 0.383 0.309 0.443. 0.217 0.459 0.0506 0.0938 0.0788 0.0780 0.0767 0.0580 0.0874 0.0435 0.0810 11.635 24.213 20.886 18.433 18.449 15.862 22.161 9.9042 20.500 Mean S.D. 21.084 4.0919 1019.5 2.167 0.2633 115.06 0.798 0.1551 38.564 0.087 0.0138 4.1546 3.554 0.6924 171.72 0.147 0.0410 7.5837 0.372 0.0720 18.005 0.098 0.0172 4.7634 Group : VII - 250 mg/kg/day Sex ANIMAL (Gms) LIVER FBW %BRAIN :MALES (Gms) SPLEEN tFBW tBRAIN 643174 643193 643194 643201 643215 643252 643259 643260 643298 643315 Mean S.D. 28.144 24.347 24.229 26.508 27.373 27.181 25.986 23.001 26.542 22.063 4.9672 4.6129 4.7433 4.8549 5.3620 5.4515 5.3022 5.2145 5.1428 4.6468 1375.6 1117.9 1171.0 1221.6 1368.7 1239.4 1249.3 1191.8 1220.3 1031.5 25.537 5.0298 1218.7 2.018 0.3066 103.65 0.737 0.627 0.698 0.884 0.691 0.705 0.616 0.683 0.790 0.703 0.1301 0.1188 0.1366 0.1619 0.1354 0.1414 0.1257 0.1548 0.1531 0.1481 36.022 28.788 33.736 40.737 34.550 32.148 29.615 35.389 36.322 32.866 0.713 0.1406 34.017 0.078 0.0138 3.4685 (Gms) TESTES tFBW tBRAIN 3.576 3.692 3.386 3.975 3.517 3.522 3.709 3.021 3.925 3.168 0.6311 0.6995 0.6629 0.7280 0.6889 0.7064 0.7568 0.6849 0.7605 0.6672 174.78 169.51 163.65 183.18 175.85 160.60 178.32 156.53 180.46 148.11 3.549 0.6986 169.10 0.302 0.0411 11.503 (Gms) THYMUS tFBW tBRAIN NW 0.392 0.463 0.455 0.331 0.270 0.445 0.310 0.295 0.276 0.0743 0.0906 0.0833 0.0648 0.0542 0.0908 0.0703 0.0572 0.0581 17.998 22.378 20.968 16.550 12.312 21.394 16.062 13.563 12.903 0.360 0.0715 17.125 0.080 0.0142 3.8158 FBW Final Body Weight 858 Company Sanitized. Does not con H-24516: Subchronic Tpxicity 90-Day Gavage Study in Rats with One-Generation Reproduction Evaluations INDIVIDUAL ANIMAL FINAL BODY AND ORGAN WEIGHTS FOR MALE RATS DESIGNATED FOR ONE-MONTH RECOVERY EVALUATION Group : I ANIMAL - 0 mg/kg/day Sex :MALES F8W (Gins) BRAIN (Gms) %FBW ADRENAL GLANDS (Gms) %FBW %BRAIN EPIDIDYMIDES (Gins) %FBW %BRAIN (Gms) HEART %FBW %BRAIN 643162 643172 643195 643226 643237 643246 643253 643262 643303 643304 Mean S.D. 419.20 648.90 597.40 590.10 516.00 677.20 635.30 650.30 656.10 516.00 590.65 82.533 2.104 2.210 2.204 2.082 1.996 2.216 2.066 2.369 2.158 2.105 0.5019 0.3406 0.3689 0.3528 0.3868 0.3272 0.3252 0.3643 0.3289 0.4079 2.151 0.3705 0.105 0.0536 0.053 0.062 0.056 0.046 0.039 0.065 0.053 0.068 0.046 0.062 0.0126 0.0096 0.0094 0.0078 0.0076 0.0096 0.0083 0.0105 0.0070 0.0120 2.5190 2.8054 2.5408 2.2094 1.9539 2.9332 2.5653 2.8704 2.1316 2.9454 0.055 0.0094 2.5475 0.009 0.0019 0.3526 1.332 1.617 1.551 1.204 1.539 1.843 1.171 1.506 1.683 1.659 0.3177 0.2492 0.2596 0.2040 0.2983 0.2722 0.1843 0.2316 0.2565 0.3215 63.308 73.167 70.372 57.829 77.104 83.168 56.680 63.571 77.989 78.812 1.511 0.2595 70.200 0.215 0.0454 9.3499 1.463 1.749 1.986 1.592 2.236 1.803 1.787 1.950 1.756 1.547 0.3490 0.2695 0.3324 0.2698 0.4333 0.2662 0.2813 0.2999 0.2676 0.2998 69.534 79.140 90.109 76.465 112.02 81.363 86.496 82.313 81.372 73.492 1.787 0.3069 83.231 0.229 0.0528 11.737 Group : VII - 250 ing/kg/day Sex :MALES ANIMAL FBW (Gms) BRAIN (Gins) %FBW ADRENAL GLANDS (Gms) %PBW %BRAIN 643151 643165 643220 643225 643234 643236 643258 643266 643296 643316 Mean S.D. 472.60 533.80 490.80 558.10 541.30 542.00 515.70 562.60 602.20 560.70 537.98 37.554 2.188 2.081 2.048 2.154 2.208 2.101 2.230 2.202 2.175 2.096 0.4630 0.3898 0.4173 0.3860 0.4079 0.3876 0.4324 0.3914 0.3612 0.3738 2.148 0.4010 0.062 0.0300 0.051 0.054 0.054 0.035 0.060 0.061 0.053 0.052 0.062 0.057 0.0108 0.0101 0.0110 0.0063 0.0111 0.0113 0.0103 0.0092 0.0103 0.0102 2.3309 2.5949 2.6367 1.6249 2.7174 2.9034 2.3767 2.3615 2.8506 2.7195 0.054 0.0101 2.5116 0.008 0.0015 0.3706 EPIDIDYMIDES (Gms) %FBW %BRAIN 1.592 1.555 0.998 5.417 1.551 1.563 1.296 1..812 1.519 1.683 0.3369 0.2913 0.2033 0.9706 0.2865 0.2884 0.2513 0.3221 0.2522 0.3002 72.761 74.724 48.730 251.49 70.245 74.393 58.117 82.289 69.839 80.296 1.899 0.3503 88.288 1.256 0.2213 58.207 (Gms) HEART %FBW %BRAIN 1.507 1.830 1.671 1.751 1.734 1.696 1.622 1.690 1.713 1.817 0.3189 0.3428 0.3405 0.3137 0.3203 0.3129 0.3145 0.3004 0.2845 0.3241 68.876 87.938 81.592 81.291 78.533 80.723 72.735 76.748 78.759 86.689 1.703 0.3173 79.388 0.094 0.0172 5.7690 (Gms) 3.616 4.075 3.509 3.752 3.582 4.190 4.268 4.300 4.642 3.284 3.922 0.434 (Gms) 4.220 4.466 3.747 5.110 4.870 4.634 3.869 4.715 4.923 4.706 4.526 0.451 FBW - Final Body Weight 859 Company Sanitized. Does not conta  H-24516: Subchronic Toxicity 90-Day Gavage Study in Rats with One-Generation Reproduction Evaluations INDIVIDUAL ANIMAL FINAL BODY AND ORGAN WEIGHTS FOR MALE RATS DESIGNATED FOR ONE-MONTH RECOVERY EVALUATION 3roup : I - 0 mg/kg/day Sex ;MALES ANIMAL (Gms) LIVER %FBW %BRAIN (Gms) SPLEEN %FBW %BRAIN (Gms) TESTES %FBW %BRAIN (Gms) THYMUS %FBW %BRAIN 643162 643172 643195 643226 643237 643246 643253 643262 643303 643304 Mean S.D. 10.852 16.681 15.905 14.428 15.272 17.881 16.290 16.405 16.410 12.941 2.5887 2.5707 2.6624 2.4450 2.9597 2.6404 2.5641 2.5227 2.5011 2.5079 515.78 754.80 721.64 692.99 765.13 806.90 788.48 692.49 760.43 614.77 15.307 2.5963 711.34 2.068 0.1435 88.595 0.462 0.800 0.728 0.841 0.819 1.063 0.897 0.770 0.738 0.788 0.1102 0.1233 0.1219 0.1425 0.1587 0.1570 0.1412 0.1184 0.1125 0.1527 21.958 36.199 33.031 40.394 41.032 47.969 43.417 32.503 34.198 37.435 0.791 0.1338 36.814 0.151 0.0187 7.1480 3.272 3.515 3.395 2.870 3.690 4.391 3.141 3.762 2.994 3.009 0.7805 0.5417 0.5683 0.4864 0.7151 0.6484 0.4944 0.5785 0.4563 0.5831 155.51 159.05 154.04 137.85 184.87 198.15 152.03 158.80 138.74 142.95 3.404 0.5853 158.20 0.459 0.1032 19.427 0.277 0.0661 0.502 0.0774 0.367 0.0614 0.247 0.0419 0.204 0.0395 0.283 0.0418 0.253 0.0398 0.371 0.0571 Q.373'0.0569 0.160 0.0310 13.165 22.715 16.652 11.864 10.220 12.771 12.246 15.661 17-285 7.6009 0.304 0.0513 14.018 0.100 0.0146 4.2375 Group : VII - 250 ANIMAL (Gms) mg/kg/day Sex LIVER tPBW tBRAIN :MALES (Gms) SPLEEN %FBW %BRAIN 643151 643165 643220 643225 643234 643236 643258 643266 643296 643316 15.674 18.089 15.720 20.721 20.334 19.595 16.997 18.904 20.729 23.195 3.316"5 3.3887 3.2029 3.7128 3.7565 3.6153 3.2959 3.3601 3.4422 4.1368 716.36 869.25 767.58 961.98 920.92 932.65. 762.20 858.49 953.06 1106.6 0.893 0.763 0.820 1.063 0.873 0.722 0.706 0.664 0.815 0.956 0.1890 0.1429 0.1671 0.1905 0.1613 0.1332 0.1369 0.1180 0.1353 0.1705 40.814 36.665 40.039 49.350 39.538 34.365 31.659 30.154 37.471 45.611 Mean S.D. 18.996 3.5228 884.91 2.412 0.2835 116.19 0.828 0.1545 38.567 0.123 0.0248 5.9162 (Gms) TESTES %PBW %BRAIN 3.897 3.749 1.983 3.798 3.434 3.553 3.002 3.636 3.027 .3.457 0.8246 0.7023 0.4040 0.6805 0.6344 0.6555 0.5821 0.6463 0.5027 0.6166 178.11 180.15 96.826 176.32 155.53 169.11 134.62 165.12 139.17 164.93 3.354 0.6249 155.99 0.567 0.1136 25.953 (Gins) THYMUS %FBW %BRAIN 0.226 0.219 0.346 0.318 0.344 0.139 0.372 0.271 0.317 0.398 0.0478 0.0410 0.0705 0.0570 0.0636 0.0256 0.0721 0.0482 0.0526 0.0710 10.329 10.524 16.895 14.763 15.580 6.6159 16.682 12.307 14.575 18.989 0.295 0.0549 13.726 0.080 0.0150 3.7426 FBW - Final Body Weight 860 Company Sanitized. Does not contain  H-24516: Subchronic Toxicity 90-Day Gavage Study in Rats with One-Generation Reproduction Evaluations INDIVIDUAL ANIMAL FINAL BODY AMD ORGAN WEIGHTS FOR MALE RATS DESIGNATED FOR THREE-MONTH RECOVERY EVALUATION Group : I - 0 nig/kg/day ANIMAL FBW (Gins) (Gms) Sex :MALES KIDNEYS tFBW (Gma) LIVER %FBW (Gms) TESTES %FBW THYROID GLAND (Gms) tFBW 643145 643210 643232 643265 643268 Mean S.D. 557.80 606.20 617.50 576.90 687.80 609.24 49.853 3.665 4.696 4.159 4.148 4.453 0.6570 0.7747 0.6735 0.7190 0.6474 4.224 0.6943 0.387 0.0526 15.836 16.402 16.538 16.530 19.012 2.8390 2.7057 2.6782 2.8653 2.7642 16.864 2.7705 1.235 0.0813 3.207 4.177 3.512 3.643 4.148 0.5749 0.6890 0.5687 0.6315 0.6031 3.737 0.6135 0.419 0.0491 0.023 0.022 0.026 0.029 0.023 0.0041 0.0036 0.0042 0.0050 0.0033 0.025 0.0041 0.003 0.0006 Group : III - 25 I ANIMAL FBW (Gins) mg/kg/dsy Sex :MALES (Gms) KIDNEYS tFBW 643202 643293 643305 643306 643310 Mean S.D. 523.60 620.20 644.70 514.80 618.70 584.40 60.488 4.108 4.571 4.531 3.090 4..329 0.7846 0.7370 0.7028 0.6002 0.6997 4.126 0.7049 0.608 0.0678 (Gms) LIVER tFBW 14.756 15.455 16.640 13.123 14.482 2.8182 2.4919 2.5810 2.5491 2.3407 14.891 2.5562 1.293' 0.1731 (Gms) TESTES tFBW 4.385 3.564 3.967 3.244 3.412 0.8375 0.5747 0.6153 0.6301 0.5515 3.714 0.6418 0.461 0.1138 THYROID GLAND (Gms) tFBW 0.018 0.026 0.023 0.015 0.024 0.0034 0.0042 0.0036 0.0029 0.0039 0.021 0.0036 0.005 0.0005 FBW - Final Body Weight 861 Company Sanitized. Does not conta H-24516: Subchronic Toxicity 90-Day Gavage Study in Rats with One-Generation Reproduction Evaluations INDIVIDUAL ANIMAL FINAL BODY AND ORGAN WEIGHTS FOR MALE RATS DESIGNATED FOR THREE-MONTH RECOVERY EVALUATION Group : V - 100 m9/kg/day Sex :MALES ANIMAL FBW (Gms) (Gms) KIDNEYS FBW 643159 643169 643181 643206 643286 Mean S.D. 608.80 555.30 729.90 534.30 558.50 597.36 78.983 4.267 4.278 4.386 4.186 3.895 0.7009 0.7704 0.6009 0.7835 0.6974 4.202 0.7106 0.186 0.0728 ANIMAL 643149 643152 643178 643283 643295 Mean S.D. 250 mg/kg/day Sex :MALES FBW (Gms) (Gms) KIDNEYS %FBW 619.10 770.50 457.70 575.20 522.50 4.260 5.835 4.031 4:092 4.236 0.6881 0.7573 0.8807 0.7114 0.8107 589.00 118.00 4.491 0.7696 0.758 0.0778 (Gms) LIVER %FBW 18.278 15.727 19.257 17.415 15.356 3.0023 2.8322 2.6383 3.2594 2.7495 17.207 2.8963 1.659 0.2425 (Gms) LIVER %FBW 20.372 23.913 14.293 18.797 15.313 3.2906 3.1036 3.1228 3.2679 2.9307 18.538 3.1431 3.897 0.1453 {Gms) TESTES %FBW 4.082 3.187 4.697 3.756 3.081 0.6705 0.5739 0.6435 0.7030 0.5517 3.761 0.6285 0.665 0.0641 (Gms) TESTES %PBW 3.958 4.128 3.183 3.459 3.805 0.6393 0.5358 0.6954 0.6014 0.7282 3.707 0.6400 0.383 0.0762 THYROID GLAND (Gms) tPBW 0.022 0.026 0.019 0.028 0.029 0.0036 0.0047 0.0026 0.0052 0.0052 0.025 0.0043 0.004 0.0011 THYROID GLAND (Gms) %FBW 0.021 0.026 0.020 0.023 0.028 0.0034 0.0034 0.0044 0.0040 0.0054 0.024 0.0041 0.003 0.0008 FBW - Final Body Weight 862 ^te^^^ H-24516: Subchronic Toxicity 90-Day Gavage Study in Rats with One-Generation Reproduction Evaluations INDIVIDUAL ANIMAL FINAL BODY AND ORGAN WEIGHTS FOR FEMALE RATS DESIGNATED FOR 90-DAY EXPOSURE EVALUATION Group : II ANIMAL - 0 nig/kg/day Sex PBW (Gms) BRAIM (Gms) tFBW : FEMALES ADRENAL GLANDS (Gms) %FBW BRAIN (Gms) HEART %FBW tBRAIN (Gms) KIDNEYS tPBW %BRAIN 643354 643361 643362 643374 643398 643406 643436 643463 643477 6434B6 Mean S.D. 280.00 373.00 303.50 301.20 290.20 260.40 304.20 331.30 285.40 245.30 297.45 35.815 1.777 1.911 1.906 1.799 2.032 1.871 1.811 1.946 1.871 1.915 0.6346 0.5123 0.6280 0.5973 0.7002 0.7185 0.5953 0.5874 0.6556 0.7807 1.884 0.6410 0.076 0.0766 0.061 0.080 0.056 0.055 0.079 0.055 0.065 0.079 0.062 0.057 0.0218 0.0214 0.0185 0.0183 0.0272 0.0211 0.0214 0.0238 0.0217 0.0232 3.4328 4.1863 2.9381 3.0573 3.8878 2.9396 3.5892 4.0596 3.3137 2.9765 0.065 0.0218 3.4381 0.010 0.0026 0.4765 0.865 1.137 1.085 1.036 1.103 0.887 1.033 1.098 0.960 0.831 0.3089 0.3048 0.3575 0.3440 0.3801 0.3406 0.3396 0.3314 0.3364 0.3388 48.678 59.498 56.925 57.588 54.281 47.408 57.040 56.423 51.309 43.394 1.004 0.3382 53.255 0.110 0.0216 5.2999 2.005 2.400 1.979 2.068 2.107 1.778 2.098 2.342 2.171 1.740 0.7161 0.6434 0.6521 0.6866 0.7261 0.6828 0.6897 0.7069 0.7607 0.7093 112.83 125.59 103.83 114.95 103.69 95.029 115.85 120.35 116.03 90.862 2.069 0.6974 109.90 0.211 0.0346 11.163 Sroup : IV - 25 mg/kg/day Sex :FEMALES ANIMAL FBW (Gins) BRAIN (Gms). PBW ADRENAL GLANDS (Gms) tFBW %BRAIN 643324 643364 643380 643389 643390 643396 643410 643433 643458 290.60 288.70 321.10 280.50 274.30 340.40 312.50 337.10 287.80 2.136 1.848 2.078 2.061 1.934 1.989 2.039 1.829 1.953 0.7350 0.6401 0.6472 0.7348 0.7051 0.5843 0.6525 0.5426 0.6786 0.057 0.070 0.061 0.073 0.060 0.085 0.065 0.057 0.063 0.0196 0.0242 0.0190 0.0260 0.0219 0.0250 0.0208 0.0169 0.0219 2.6685 3.7879 2.9355 3.5420 3.1024 4.2735 3.1878 3.1165 3.2258 Mean S.D. 303.67 24.735 1.985 0.6578 0.104 0.0649 0.066 0.0217 3.3155 0.009 0.0030 0.4828 (Gma) HEART tFBW %BRAIN 1.047 0.883 1.058 1.062 1.088 1.276 1.069 1.716 1.048 0.3603 0.3059 0.3295 0.3786 0.3966 0.3749 0.3421 0.5090 0.3641 49.017 47.781 50.914 51.528 56.256 64.153 52.428 93.822 53.661 1.139 0.3734 57.729 0.238 0.0578 14.364 (Gms) KIDNEYS %FBW %BRAIN 2.267 1.828 2.513 2.315 2.276 2.758 2.639 2.058 2.439 0.7801 0.6332 0.7826 0.8253 0.8297 0.8102 0.8445 0.6105 0.8475 106.13 98.918 120.93 112.32 117.68 138.66 129.43 112.52 124.88 2.344 0.7737 117.94 0.286 0.0895 12.149 (Gms) 7.697 9.431 8.409 9.159 8.431 7.670 9.145 9.612 7.794 6.941 8.429 0.893 (Gms) 8.814 8.713 9.167 9.652 8.436 12.620 8.619 8.877 8.711 9.290 1.298 FBW - Final Body Weight 863 Company Sanitized. Does not contai H-24516: Subchronic Toxicity 90-Day Gavage Study in Rats with One-Generation Reproduction Evaluations INDIVIDUAL ANIMAL FINAL BODY AND ORGAN WEIGHTS FOR FEMALE RATS DESIGNATED FOR 90-DAY EXPOSURE EVALUATION Group : V? - 100 mg/kg/day Sex : FEMALES ANIMAL FBW (Gms) BRAIN (Gms) PBW ADRENAL GLANDS (Gms) tFBW tBRAIN (Gms) HEART FBW %BRAIN (Gms) KIDNEYS %FBW tBRAIN 643322 643323 643366 643367 643392 643409 643461 643462 643472 643489 Mean S.D. 282.00 270.40 303.80 289.50 259.00 272.30 313.20 311.80 254.60 307.50 286.41 22.003 1.887 1.936 1.977 1.919 1.895 1.877 1.982 1.918 1.716 2.035 0.6691 0.7160 0.6508 0.6629 0.7317 0.6893 0.6328 0.6151 0.6740 0.6618 1.914 0.6703 0.085 0.0353 0.053 0.080 0.063 0.074 0.070 0.049 0.072 0.065 0.069 0.060 0.0188 0.0296 0.0207 0.0256 0.0270 0.0180 0.0230 0.0208 0.0271 0.0195 2.8087 4.1322 3.1866 3.8562 3.6939 2.6105 3.6327 3.3889 4.0210 2.9484 0.066 0.0230 3.4279 0.010 0.0041 0.5255 1.035 1.015 0.995 1.046 0.894 1.031 1.094 1.058 0.919 1.031 0.3670 0.3754 0.3275 0.3613 0.3452 0.3786 0.3493 0.3393 0.3610 0.3353 54.849 52.428 50.329 54.508 47.177 54.928 55.197 55.162 53.555 50.663 1.012 0.3540 52.879 0.062 0.0173 2.7060 2.257 0.8004 2.321 0.8584 2.226 0.7327 2.348 0.8111 2.008 0.7753 2.250 0.8263 2.782 0.8883 2.603.0.8348 2.136 0.8390 2.359 0.7672 119.61 119.89 112.59 122.36 105.96 119.87 140.36 135.71 124.48 115.92 2.329 0.8133 121.68 0.222 0.0462 10.153 3roup : VIII - 250 mg/kg/day Sex ANIMAL FBW (Gms) BRAIN (Gms) %FBW : FEMALES ADRENAL GLANDS (Qms) %FBW %BRAIN 643332 643341 643359 643370 643404 643408 643435 643446 643466 Mean S.D. 263.50 287.20 335.10 317.30 249.30 290.10 233.90 295.80 279.20 283.49 31.745 1.904 1.888 1.978 1.930 2.026 1.859 1.797 2.001 2.111 0.7226 0.6574 0.5903 0.6083 0.8127. 0.6408 0.7683 0.6765 0.7561 1.944 0.6925 0.095 0.0765 0.064 0.061 0.071 0.071 0.078 0.051 0.064 0.060 0.073 0.0243 0.0212 0.0212 0.0224 0.0313 0.0176 0.0274 0.0203 0.0261 3.3613 3.2309 3.5895 3.6788 3.8500 2.7434 3.5615 2.9985 3.4581 0.066 0.0235 3.3858 0.008 0.0042 0.3475 (GUIS) HEART %FBW %BRAIN 1.000 0.885 1.193 1.089 1.017 1.016 0.877 1.059 1.130 0.3795 0.3081 0.3560 0.3432 0.4079 0.3502 0.3749 0.3580 0.4047 52.521 46.875 60.313 56.425 50.197 54.653 48.804 52.924 53.529 1.030 0.3647 52.916 0.104 0.0312 4.0525 (Gms) KIDNEYS %FBW %BRAIN 2.313 2.474 2.878 2.689 3.075 2.404 2.329 2.736 2.550 0.8778 0.8614 0.8588 0.8475 1.2335 0.8287 0.9957 0.9249 0.9133 121.48 131.04 145.50 139.33 151.78 129.32 129.60 136.73 120.80 2.605 0.9269 133.95 0.260 0.1256 10.399 (Gms) 10.226 3 9.397 3 10.124 3 10.624 3 8.750 3 10.217 3 11.802 3 11.178 3 9.439 3 11.184 3 10.294 3 0.938 0 (Gms) 12.742 4 12.486 4 14.952 4 14.597 4 12.396 4 11.243 3 10.064 4 12.746 4 12.022 4 12.583 4 1.509 0 FBW - Final Body Weight 864 Company Sanitized. Does not contai H-24516: Subchronic Toxicity 90-Day Gavage Study in Rats with One-Generation Reproduction Evaluations INDIVIDUAL ANIMAL FINAL BODY AND ORGAN WEIGHTS FOR FEMALE RATS DESIGNATED FOR 90-DAY EXPOSURE EVALUATION Group : II - 0 ing/kg/day Sex : FEMALES ANIMAL (Gms) OVARIES %FBW tBRAIN (Gins) SPLEEN tFBW tBRAIN (Gm8) THYMUS %PBW tBRAIN (Gms) UTERUS tFBW tBRAIN 643354 643361 643362 643374 643398 643406 643436 643463 643477 643486 0.133 0.127 0.117 0.071 0.157 0.118 0.141 0.132 0.076 0.083 0.0475 0.0340 0.0386 0.0236 0.0541 0.0453 0.0464 0.0398 0.0266 0.0338 7.4845 6.6457 6.1385 3.9466 7.7264 6.3068 7.7858 6.7831 4.0620 4.3342 0.534 0.640 0.515 0.557 0.605 0.457 0.384 0.611 0.421 0.336 0.1907 0.1716 0.1697 0.1849 0.2085 0.1755 0.1262 0.1844 0.1475 0.1370 30.051 33.490 27.020 30.962 29.774 24.425 21.204 31.398 22.501 17.546 0.188 0.511 0.398 0.333 0.329 0.243 0.256 0.256 0.320 0.144 0.0671 0.1370 0.1311 0.1106 0.1134 0.0933 0.0842 0.0773 0.1121 0.0587 10.580 26.740 20.881 18.510 16.191 12.988 14.136 13.155 17.103 7.5196 0.484 0.634 0.514 0.675 0.516 0.570 0.588 0.557 0.551 0.693 0.1729 0.1700 0.1694 0.2241 0.1778 0.2189 0.1933 0.1681 0.1931 0.2825 27.237 33.176 26.967 37.521 25.394 30.465 32.468 28.623 29.449 36.188 Mean S.D. 0.116 0.0390 6.1214 0.029 0.0096 1.4950 0.506 0.1696 26.837 0.103 0.0256 5.2041 0.298 0.0985 15.780 0.106 0.0266 5.4588 0.578 0.1970 30.749 0.070 0.0363 4.0262 Group : IV - 25 ing/kg/day Sex : FEMALES ANIMAL (Gms) OVARIES %FBW tBRAIN (Gms) SPLEEN %PBW BRAIN 643324 643364 643380 643389 643390 643396 643410 643433 643458 0.118 0.105 0.146 0.135 0.109 0.098 0.151 0.117 0.120 0.0406 0.0364 0.0455 0.0481 0.0397 0.0288 0.0483 0.0347 0.0417 5.5243 5.6818 7.0260 6.5502 5.6360 4.9271 7.4056 6.3969 6.1444 0.537 0.496 0.473 0.493 0.445 0.615 0.565 0.486 0.445 0.1848 0.1718 0.1473 0.1758 0.1622 0.1807 0.1808 0.1442 0.1546 25.140 26.840 22.762 23.920 23.009 30.920 27.710 26.572 22.785 Mean S.D. 0.122 0.0404 6.1436 0.018 0.0065 0.7854 0.506 0.1669 25.518 0.056 0.0153 2.7589 (Gins) THYMUS %FBW tBRAIN 0.269 0.171 0.347 0.306 0.309 0.231 0.388 0.441 0.348 0.0926 0.0592 0.1081 0.1091 0.1127 0.0679 0.1242 0.1308 0.1209 12.594 9.2532 16.699 14.847 15.977 11.614 19.029 24.112 17.819 0.312 0.1028 15.771 0.082 0.0249 4.4157 (Gms) UTERUS tFBW tBRAIN 0.959 0.503 0.549 0.413 0.929 0.653 0.978 0.454 0.513 0.3300 0.1742 0.1710 0.1472 0.3387 0.1918 0.3130 0.1347 0.1782 44.897 27.219 26.420 20.039 48.035 32.831 47.965 24.822 26.267 0.661 0.2199 33.166 0.230 0.0825 10.887 FBW - Final Body weight 865 Company Sanitized. Does not contain H-24516: Subchronic Toxicity 90-Day Gavage Study in Rats with One-Generation Reproduction Evaluations INDIVIDUAL ANIMAL FINAL BODY AND ORGAN WEIGHTS FOR FEMALE RATS DESIGNATED FOR 90-DAY EXPOSURE EVALUATION Group : VI - 100 mg/kg/day Sex :FEMALES ANIMAL (Gms) OVARIES FBW tBRAIN (Gms) SPLEEN tFBW tBRAIM (Gms) THYMUS %FBW %BRAIN (Gms) UTERUS FBW tBRAIN 643322 . 0.113 0.0401 5.9883 643323 0.149 0.0551 7.6963 643366 0.157 0.0517 7.9413 643367 0.103 0.0356 5.3674 643392 0.128 0.0494 6.7546 643409 643461 0.133 0.0488 7.0858 0.150 0.0479 7.5681 643462 643472 0.120 0.0385 6.2565 0.121 0.0475 7.0513 643489 0.113 0.0367 5.5528 0.436 0.662 0.507 0.427 0.398 0.423 0.642 0.652 0.445 0.479 0.1546 0.2448 0.1669 0.147S 0.1537 0.1553 0.2050 0.2031 0.1748 0.1558 23.105 34.194 25.645 22.251 21.003 22.536 32.392 33.994 25.932 23.538 0.344 0.1220 18.230 . 0.288 0.1065 14.876 0.249 0.0820 12.595 0.395 0.1364 20.584 0.201 0.0776 10.607 0.329 0.1208 17.528 0.304 0.0971 15.338 0.314 0.1007 16.371 0.211 0.0829 12.296 0.215 0.0699 10.565 0.539 0.743 0.604 0.647 0.498 0.386 0.639 0.657 0.603 0.491 0.1911 0.2748 0.1988 0.2235 0.1923 0.1418 0.2040 0.2107 0.2368 0.1597 28.564 38.378 30.551 33.715 26.280 20.565 32.240 34.254 35.140 24.128 Mean S.D. 0.129 0.0451 6.7262 0.018 0.0068 0.9037 0.507 0.1767 26.459 0.104 0.0322 5.1141 0.285 0.0996 14.899 0.065 0.0219 3.3660 0.581 0.2034 30.382 0.103 0.0375 5.4954 Group : VIII - 2SO mg/kg/day Sex ANIMAL (Gins) OVARIES tPBW tBRAIN ;FEMALES (Gms) SPLEEN %FBW %BRAIN 643332 643341 643359 643370 643404 643408 64343S 643446 643466 Mean S.D. 0.102 0.0387 5.3571 0,424 0.1609 22.269 0.103 0.0359 5.4555 0.424 Q.1476'22.458 0.140 0.0418 7.0779 0.645 0.1925 32.609 0.093 0.0293 4.8187 0.540 0.1702 27.979 0.139 0.0558 6.8608. 0.528 0.2118 26.061 0.117 0.0403 6.2937 0.555 0.1913 29.855 0.103 0.0440 5.7318 0.470 0.2009 26.155 0.104 0.0352 5.1974 0.617 0.2086 30.835 0.100 0.0358 4.7371 0.528 0.1891 25.012 0.111 0.0396 5.7256 0.017 0.0074 0.8461 0.526 0.1859 27.026 0.077 0.0219 3.6026 (Gms) THYMUS %PBW %BRAIN 0.209 0.258 0.505 0.284 0.221 0.302 0.298 0.202 0.281 0.0793 0.0898 0.1507 0.0895 0.0886 0.1041 0.1274 0.0683 0.1006 10.977 13.665 25.531 14.715 10.908 16.245 16.583 10.095 13.311 0.284 0.0998 14.670 0.091 0.0253 4.6861 (Gms) UTERUS %FBW %BRAIN 0.917 0.850 0.702 0.429 0.367 0.486 0.828 0.656 0.745 0.3480 0.2960 0.2095 0.1352 0.1472 0.1675 0.3540 0.2218 0.2668 48.162 45.021 35.490 22.228 18.115 26.143 46.077 32.784 35.291 0.664 0.2384 34.368 0.196 0.0826 10.751 FBW - Final Body Weight 866 C.nWSanlze-.ooo>~ni H-24516: Subchronic Toxicity 90-Day Gavage Study in Rats with One-Generation Reproduction Evaluations INDIVIDUAL ANIMAL FINAL BODY AND ORGAN WEIGHTS FOR FEMALE RATS DESIGNATED FOR ONE-MONTH RECOVERY EVALUATION Sroup : II ANIMAL - 0 mg/kg/day Sex FBW (Gms) BRAIN (Gms) %FBW :FEMALES ADRENAL GLANDS (Gms) %FBW BRAIN (GTOS) HEART %FBW %BRAIN (Gms) KIDNEYS %FBW %BRAIN 643330 643377 643387 643405 643415 643425 643426 643448 643453 Mean S.D. 278.80 356.00 334.20 375.20 414.90 365.00 376.00 329.20 348.70 353.11 37.832 1.784 1.893 2.004 1.915 1.940 1.982 1.870 2.009 1.955 0.6399 0.5317 0.5996 0.5104 0.4676 0.5430 0.4973 0.6103 0.5607 1.928 0.5512 0.072 0.0568 0.053 0.066 0.077 0.085 0.087 0.055 0.055 0.062 0.059 0.0190 0.0185 0.0230 0.0227 0.0210 0.0151 0.0146 0.0188 0.0169 2.9709 3.4865 3.8423 4.4386 4.4845 2.7750 2.9412 3.0861 3.0179 0.067 0.0189 3.4492 0.013 0.0030 0.6582 1.207 1.151 1.125 1.117 1.331 1.202 1.331 1.026 1.079 0.4329 0.3233 0.3366 0.2977 0.3208 0.3293 0.3540 0.3117 0.3094 67.657 60.803 56.138 58.329 68.608 60.646 71.176 51.070 55.192 1.174 0.3351 61.069 0.105 0.0402 6.7915 2.209 2.706 2.396 2.264 2.843 2.429 2.243 2.187 2.654 0.7923 0.7601 0.7169 0.6034 0.6852 0.6655 0.5965 0.6643 .0.7611 123.82 142.95 119.56 118.22 146.55 122.55 119.95 108.86 135.75 2.437 0.6939 126.47 0.242 0.0694 12.508 (Gms) 8.689 3 11.099 3 8.682 2 10.447 2 13.441 3 9.244 2 10.833 2 7.944 2 10.507 3 10.098 2 1.672 0 Sroup : VIII - 250 mg/kg/day Sex ANIMAL FBM (Gms) BRAIN (Gms) %FBW : FEMALES ADRENAL GLANDS (Gms) %FBW %BRAIN 643345 643347 643351 643358 643423 643441 643444 643456 643474 643481 Mean S.D. 313.00 263.40 286.30 352.20 294.70 365.40 312.70 326.60 272.00 299.50 308.S8 32.733 1.892 1.839 1.853 1.782 1.932 1.891 2.024 2.114 1.879 1.912 0.6045 0.6982 0.6472 0.5060 0.6556 0.5175 0.6473 0.6473 0.6908 0.6384 1.912 0.6253 0.095 0.0653 0.091 0.0291 4.8097 0.074 0.0281 4.0239 0.075 0.0262 4.0475 0.065 0.0185 3.6476 0.094 0.0319 4.8654 0.061 0.0167 3.2258 . 0.072 0.0230 3.5573 0.075 0.0230 3.5478 0.069 0.0254 3.6722 0.068 0.0227 3.5565 0.074 0.0244 3.8954 0.011 0.0047 0.5504 (Gms) HEART %FBW %BRAIN 1.145 0.948 1.028 1.111 1.165 1.058 1.209 1.122 1.090 0.951 0.3658 0.3599 0.3591 0.3154 0.3953 0.2895 0.3866 0.3435 0.4007 0.3175 60.518 51.550 55.478 62.346 60.300 55.949 59.733 53.075 58.010 49.738 1.083 0.3534 56.670 0.087 0.0369 4.2230 (Gms) KIDNEYS tFBW %BRAIN 2.393 2.320 2.282 2.222 2.311 2.699 3.458 2.888 2.092 2.408 0.7645 0.8808 0.7971 0.6309 0.7842 0.7386 1.1059 0.8843 0.7691 0.8040 126.48 126.16 123.15 124.69 119.62 142.73 170.85 136.61 111.34 125.94 2.507 0.8159 130.76 0.406 0.1245 16.478 (Gms) 9.195 2 8.942 3 8.176 2 10.438 2 11.520 3 10.501 2 11.910 3 11.658 3 8.467 3 9.126 3 9.993 3 1.389 0 FBW - Final Body Weight 867 Company Sanitized. Does not contain TSC H-24516: Subchronic Toxicity 90-Day Gavage Study in Rats with One-Generation Reproduction Evaluations INDIVIDUAL ANIMAL FINAL BODY AMD ORGAN WEIGHTS FOR FEMALE RATS DESIGNATED FOR ONE-MONTH RECOVERY EVALUATION Group : II - 0 mg/kg/day Sex ANIMAL |(Gms) OVARIES tFBW tBRAIN :FEMALES (Gms) SPLEEN tFBW tBRAIN (Gms) THYMUS tFBW tBRAIN (Gms) UTERUS tPBW tBRAIN 643330 643377 643387 643405 643415 643425 643426 643448 643453 0.067 0.078 0.127 0.134 0.108 0.127 0.100 0.148 0.150 0.0240 0.0219 0.0380 0.0357 0.0260 0.0348 0.0266 0.0450 0.0430 3.7556 4.1204 6.3373 6.9974 5.5670 6.4077 5.3476 7.3668 7.6726 0.575 0.581 0.474 0.744 0.608 0.460 0.545 0.524 0.595 0.2062 0.1632 0.1418 0.1983 0.1465 0.1260 0.1449 0.1592 0.1706 32.231 30.692 23.653 38.851 31.340 23.209 29.144 26.083 30.435 0.232 0.280 0.164 0.404 0.382 0.244 0.263 0.207 0.239 0.0832 0.0787 0.0491 0.1077 0.0921 0.0668 0.0699 0.0629 0.0685 13.004 14.791 8.1836 21.097 19.691 12.311 14.064 10.304 12.225 0.612 0.689 1.025 0.505 0.805 0.669 0.736 0.625 0.569 0.2195 0.1935 0.3067 0.1346 0.1940 0.1833 0,1957 .0.1899 0.1632 34.305 36.397 51.148 26.371 41.495 33.754 39.358 31.110 29.105 Mean S.D. 0.115 0.0328 5.9525 0.029 0.0085 1.3740 0.567 0.1619 29.515 0.084 0.0264 4.8238 0.268 0.0754 13.963 0.078 0.0173 4.1511 0.693 0.1978 35.894 0.153 0.0472 7.4421 Group : VIII 250 mg/kg/day Sex ;FEMALES I ANIMAL (Gms) OVARIES tFBW tBRAIN | |(Gms) SPLEEN tFBW tBRAIN 643345 643347 643351 643358 643423 643441 643444 643456 643474 643481 Mean S.D. 0.135 0.114 0.095 0.109 0.078 0.132 0.116 0.135 0.134 0.129 0.043-1 0.0433 0.0332 0.0309 0.0265 0.0361 0.0371 0.0413 0.0493 0.0431 7.1353 6.1990 5.1268 6.1167 4.0373 6.9804 5.7312 6.3860 7.1315 6.7469 0.118 0.0384 6.1591 0.019 0.0069 0.9846 0.505 0.449 0.394 0.451 0.882 0.611 0.516 0.593 0.503 0.470 0.1613 0.1705 0.1376 0.1281 0.2993 0.1672 0.1650 0.1816 0.1849 0.1569 26.691 24.415 21.263 25.309 45.652 32.311 25.494 28.051 26.770 24.582 0.537 0.1752 28.054 0.138 0.0470 6.8055 (Gms) THYMUS tFBW tBRAIN 0.283 0.143 0.176 0.187 0.298 0.227 0.238 0.259 0.260 0.208 0.0904 0.0543 0.0615 0.0531 0.1011 0.0621 0.0761 0.0793 0.0956 0.0694 14.958 7.7760 9.4981 10.494 15.424 12.004 11.759 12.252 13.837 10.879 0.228 0.0743 11.888 0.049 0.0171 2.3915 (Gms) UTERUS tFBW tBRAIN 0.592 0.710 0.643 0.639 0.719 1.224 0.700 0.615 0.586 0.463 0.1891 0.2696 0.2246 0.1814 0.2440 0.3350 0.2239 0.1883 0.2154 0.1546 31.290 38.608 34.700 35.859 37.215 64.728 34.585 29.092 31.187 24.215 0.689 0.2226 36.148 0.202 0.0516 10.899 FBW - Final Body Weight 868 Company Sanitized. Does not contain H-24516: Subchronic Toxicity 90-Day Gavage Study in Rats with One-Generation Reproduction Evaluations INDIVIDUAL ANIMAL FINAL BODY AND ORGAN WEIGHTS FOR FEMALE RATS DESIGNATED FOR THREE-MONTH RECOVERY EVALUATION Group : II ] ANIMAL - 0 mg/kg/day Sex :FEMALES FEW (Gms) (Gms) KIDNEYS %FBW (Gms) LIVER %FBW THYROID GLAND (Gms) %FBW 643383 643384 643402 643465 643484 312.70 315.00 294.90 345.90 294.60 2.305 2.085 2.222 2.541 2.451 0.7371 0.6619 0.7535 0.7346 0.8320 10.212 8.456 7.891 10.237 8.697 3.2657 2.6844 2.6758 2.9595 2.9521 0.018 0.016 0.017 0.017 0.015 0.0058 0.0051 0.0058 0.0049 0.0051 Mean S.D. 312.62 20.928 2.321 0.7438 0.181 0.0606 9.099 2.9075 1.069 0.2431 0.017 0.0053 0.001 0.0004 Group : IV - 25 nig/kg/day Sex : FEMALES ANIMAL FBW (Gms) (Gms) KIDNEYS %PBW 643379 643391 643437 643483 368.10 326.80 343.10 299.70 2.367 0.6430 2.262 0.6922 2.505 0.7301 2.614 0.8722 Mean S.D. 334.43 28.713 2.437 0.7344 0..154 0.0986 (Gms) LIVER %FBW 10.036 2.7264 9.563 2.9263 9.046 2.6365 8.265 2.7578 9.228 2.7617 0.758 0.1211 THYROID GLAND (Gms) %FBW 0.014 0.0038 0.017 0.0052 0.018 0.0052 0.024 0.0080 0.018 0.0056 0.004 0.0018 FBW - Final Body Weight 869 Company Sanitized. Does not contain H-24516: Subchronic Toxicity 90-Day Gavage Study in Rats with One-Generation Reproduction Evaluations AMIMAL 643360 643373 643381 643382 643412 Mean S.D. INDIVIDUAL ANIMAL FINAL BODY AND ORGAN WEIGHTS FOR FEMALE RATS DESIGNATED FOR THREE-MONTH RECOVERY EVALUATION 100 mg/kg/day Sex :FEMALES FEW (Gms) (Gms) KIDNEYS %FBW (Gms) LIVER %FBW THYROID GLAND (Gms) %FBW 277.70 356.80 328.10. 286.10 327.20 315.18 32.764 2.342 2.963 2.302 2.511 2.221 0.8434 0.8304 0.7016 0.8777 0.6788 2.468 0.7864 0.296 0.0898 8.488 11.626 9.562 9.100 9.309 3.0565 3.2584 2.9144 3.1807 2.8450 9.617 3.0510 1.191 0.1739 0.019 0.019 0.016 0.025 0.017 0.0068 0.0053 0.0049 0.0087 0.0052 0.019 0.0062 0.003 0.0016 Group : VIII - 250 mg/kg/day Sex ANIMAL PBW (Gms) (Gms) KIDNEYS tFBW :FEMALES (Gms) LIVER %FBW 643329 643356 643388 643450 643487 Mean S.D. 368.90 341.10 286.10 429.70 312.00 347.56 55.421 3.198 2.497 2.248 3,379 2.200 0.8669 0.7320 0.7857 0.7864 0.7051 2.704 0.7752 0.549 0.0621 11.876 11.657 9.323 12.632 9.954 3.2193 3.4175 3.2587 2.9397 3.1904 11.088 3.2051 1.390 0.1723 THYROID GLAND (Gms) %FBW 0.017 0.015 0.021 0.020 0.024 0.0046 0.0044 0.0073 0.0047 0.0077 0.019 0.0057 0.004 0.0016 FBW - Final Body Weight 870 Company Sanitized. Does not conta APPENDIX N INDIVIDUAL ANIMAL GROSS AND MICROSCOPIC OBSERVATIONS 871 Company Sanitized. Don not contain TSCA CBl  H-24516: Subchronic Toxicity 90-Day Gavage Study in Rats with One-Generation Reproduction Evaluations INDIVIDUAL ANIMAL GROSS AND MICROSCOPIC OBSERVATIONS Dose Group : I - 0 mg/kg/day Sex: Males Animal Ref Microscopic & Macroscopic Findings 643143 Terminal Sacrifice Killed on Day : 91 Exposure Group : 90-DAY EXPOSURE Animal is signed off from necropsy Gross Pathology : No Macroscopic Abnormality Observed : LIVER, KIDNEYS, LUNGS, HEART, SKELETAL MUSCLE, SPLEEN, AORTA, BRAIN, SPINAL CORD, STOMACH, DUODENUM, JEJUNUM, ILEUM, PANCREAS, CECUM, COLON, RECTUM, MESENTERIC LYMPH NODE, SALIVARY GLANDS, MANDIBULAR LYMPH NODE, THYMUS, ADRENAL GLANDS, SCIATIC NERVE, PITUITARY GLAND, THYROID GLAND, PARATHYROID GLANDS, TRACHEA, ESOPHAGUS, PHARYNX/LARYNX, EYE(S) WITH OPTIC NERVE, SKIN, PROSTATE, " -SEMINAL VESICLES, URINARY BLADDER, TESTES, EPIDIDYMIDES, FEMUR/KNEE JOINT, STERNUM, NOSE, MANDIBLE Histopathology : LIVER : INFLAMMATION, SUBACUTE/CHRONIC, THYROID GLAND : ALTERATION, COLLOID, minimal. minimal. No Microscopic Abnormality Observed : KIDNEYS, LUNGS, HEART, SKELETAL MUSCLE, SPLEEN, AORTA, BRAIN, SPINAL CORD, STOMACH, DUODENUM, JEJUNUM, ILEUM, PANCREAS, CECUM, COLON, RECTUM, MESENTERIC LYMPH NODE, SALIVARY GLANDS, MANDIBULAR LYMPH NODE, THYMUS, ADRENAL GLANDS, SCIATIC NERVE, PITUITARY GLAND, PARATHYROID GLANDS, 643143 Continued on the next page .... 872 Company Sanitized. Does not contain T  H-24516: Subchronic Toxicity 90-Day Gavage Study in Rats with One-Generation Reproduction Evaluations INDIVIDUAL ANIMAL GROSS AND MICROSCOPIC OBSERVATIONS Dose Group : I - 0 mg/kg/day Sex: Males Animal Ref Microscopic & Macroscopic Findings 643143 Continued from previous page Histopathology : No Microscopic Abnormality Observed : TRACHEA, ESOPHAGUS, PHARYNX/LARYNX, EYE(S) WITH OPTIC NERVE, SKIN, PROSTATE, SEMINAL VESICLES, URINARY BLADDER, TESTES, EPIDIDYMIDES, FEMUR/KNEE JOINT, STERNUM, BONE MARROW, NOSE, MANDIBLE 643145 Terminal Sacrifice Killed on Day : 181 Exposure Group : THREE-MONTH RECOVERY Animal is signed off from necropsy Gross Pathology : No Macroscopic Abnormality Observed : LIVER, .KIDNEYS, LUNGS, HEART, SKELETAL MUSCLE, SPLEEN, AORTA, BRAIN, SPINAL CORD, STOMACH, DUODENUM, JEJUNUM, ILEUM, PANCREAS, CECUM, COLON, RECTUM, MESENTERIC LYMPH NODE, SALIVARY GLANDS, MANDIBULAR LYMPH NODE, THYMUS, ADRENAL GLANDS, SCIATIC NERVE, PITUITARY GLAND, THYROID GLAND, PARATHYROID GLANDS, TRACHEA, ESOPHAGUS, PHARYNX/LARYNX, EYE(S) WITH OPTIC NERVE, SKIN, PROSTATE, SEMINAL VESICLES, URINARY BLADDER, TESTES, EPIDIDYMIDES, FEMUR/KNEE JOINT, STERNUM, NOSE, MANDIBLE Histopathology : 643145 LIVER : INFLAMMATION, SUBACUTE/CHRONIC, Continued on the next page .... minimal. 873 Company Sanitized. Does not conta 0 .H-24516: Subchronic Toxicity H> 90-Day Gavage Study in Rats with One-Generation Reproduction Evaluations INDIVIDUAL ANIMAL GROSS AND MICROSCOPIC OBSERVATIONS Dose Group : I - 0 ing/kg/day Sex: Males Animal Ref Microscopic & Macroscopic Findings 643145 Continued from previous page Histopathology : KIDNEYS : NEPHROPATHY, CHRONIC PROGRESSIVE, minimal. THYROID GLAND : ALTERATION, COLLOID, minimal. NOSE : INFLAMMATION, SUBACUTE/CHRONIC, minimal. HYPERPLASIA/SQUAMOUS METAPLASIA, RESPIRATORY, mild. EPITHELIUM, 643150 Terminal Sacrifice - "Killed on Day : 91 Exposure Group : 90-DAY EXPOSURE Animal is signed off from necropsy Gross Pathology ; No Macroscopic Abnormality Observed : LIVER, KIDNEYS, LUNGS, HEART, SKELETAL MUSCLE, SPLEEN, AORTA, BRAIN, SPINAL CORD, STOMACH, DUODENUM, JEJUNUM, ILEUM, PANCREAS, CECUM, COLON, RECTUM, MESENTERIC LYMPH NODE, SALIVARY GLANDS, MAMDIBULAR LYMPH NODE, THYMUS, ADRENAL GLANDS, SCIATIC NERVE, PITUITARY GLAND, THYROID GLAND, PARATHYROID GLANDS, TRACHEA, ESOPHAGUS, PHARYNX/LARYNX, EYE(S) WITH OPTIC NERVE, SKIN, PROSTATE, SEMINAL VESICLES, URINARY BLADDER, TESTES, EPIDIDYMIDES, FEMUR/KNEE JOINT, STERNUM, NOSE, MANDIBLE 643150 Continued on the next page .... 874 Company Sanitized. Does not contain H-24516: Subchronic Toxicity 90-Day Gavage Study in Rats with One-Generation Reproduction Evaluations INDIVIDUAL ANIMAL GROSS AND MICROSCOPIC OBSERVATIONS Dose Group : I - 0 mg/kg/day Sex: Males Animal Ref 643150 . Microscopic & Macroscopic Findings Continued from previous page Histopathology : LIVER : INFLAMMATION, SUBACUTE/CHRONIC, minimal. KIDNEYS : NEPHROPATHY, CHRONIC PROGRESSIVE, minimal. No Microscopic Abnormality Observed : LUNGS, HEART, SKELETAL MUSCLE, SPLEEN, AORTA, BRAIN, SPINAL CORD, STOMACH. DUODENUM, JEJUNUM, ILEUM, PANCREAS, CECUM, COLON, RECTUM, MESENTERIC LYMPH NODE, SALIVARY GLANDS, MANDIBULAR LYMPH NODE, THYMUS, ADRENAL GLANDS, SCIATIC NERVE, PITUITARY GLAND, THYROID GLAND, PARATHYROID GLANDS, TRACHEA, ESOPHAGUS, PHARYNX/LARYNX, EYE(S) WITH OPTIC NERVE, SKIN, PROSTATE, SEMINAL VESICLES, URINARY BLADDER, TESTES, EPIDIDYMIDES, FEMUR/KNEE JOINT, STERNUM,BONE MARROW, NOSE, MANDIBLE 643162 Terminal Sacrifice Killed on Day : 125 Exposure Group : ONE-MONTH RECOVERY Animal is signed off from necropsy Gross Pathology : 643162 No Macroscopic Abnormality Observed : LIVER, KIDNEYS, LUNGS, HEART, SKELETAL MUSCLE, SPLEEN, AORTA, BRAIN, SPINAL CORD, STOMACH, DUODENUM, JEJUNUM, ILEUM, PANCREAS, CECUM, COLON, RECTUM, MESENTERIC LYMPH NODE, SALIVARY GLANDS, MANDIBULAR LYMPH NODE, THYMUS. ADRENAL GLANDS, SCIATIC NERVE, PITUITARY GLAND, Continued on the next page .... 875 Company Sanitized. Does not contain TS H-24516: Subchronic Toxicity 90-Day Gavage Study in Rats with One-Generation Reproduction Evaluations INDIVIDUAL ANIMAL GROSS AND MICROSCOPIC OBSERVATIONS Dose Group : I - 0 nig/kg/day Sex: Males Animal Ref Microscopic & Macroscopic Findings 643162 . Continued from previous page Gross Pathology : No Macroscopic Abnormality Observed : THYROID GLAND, PARATHYROID GLANDS, TRACHEA, ESOPHAGUS, PHARYNX/LARYNX, EYE(S) WITH OPTIC NERVE, SKIN, PROSTATE, SEMINAL VESICLES, URINARY BLADDER, TESTES, EPIDIDYMIDES, FEMUR/KNEE JOINT, STERNUM, NOSE, MANDIBLE Histopathology : LIVER : INFLAMMATION, SUBACUTE/CHRONIC, THYROID GLAND : ALTERATION, COLLOID, minimal. NOSE : ODONTODYSPLASIA, moderate. minimal. No Microscopic Abnormality Observed : KIDNEYS, MANDIBLE 643172 Terminal Sacrifice Killed on Day : 125 Exposure Group : ONE-MONTH RECOVERY Animal is signed off from necropsy Gross Pathology : 643172 No Macroscopic Abnormality Observed : LIVER, KIDNEYS, LUNGS, HEART, SKELETAL MUSCLE, SPLEEN, AORTA, BRAIN, SPINAL CORD, STOMACH, DUODENUM, JEJUNUM, ILEUM, PANCREAS, CECUM, COLON, RECTUM, MESENTERIC LYMPH NODE, SALIVARY GLANDS, MANDIBULAR LYMPH NODE, THYMUS, ADRENAL GLANDS, SCIATIC NERVE, PITUITARY GLAND, Continued on the next page .... 876 Company Sanitized. Does not contain H-24516: Subchronic Toxicity 90-Day Gavage Study in Rats with One-Generation Reproduction Evaluations INDIVIDUAL ANIMAL GROSS AND MICROSCOPIC OBSERVATIONS Dose Group : I - 0 mg/kg/day Sex: Males Animal Ref 643172 Microscopic & Macroscopic Findings Continued from previous page Gross Pathology : No Macroscopic Abnormality Observed : THYROID GLAND, PARATHYROID GLANDS, TRACHEA, ESOPHAGUS, PHARYNX/LARYNX, EYE(S) WITH OPTIC NERVE, SKIN, PROSTATE, SEMINAL VESICLES, URINARY BLADDER, TESTES, EPIDIDYMIDES, FEMUR/KNEE JOINT, STERNUM, NOSE, MANDIBLE Histopathology ; LIVER : INFLAMMATION, SUBACUTE/CHRONIC, THYROID GLAND : ALTERATION, COLLOID, mild. . minimal. No Microscopic Abnormality Observed : KIDNEYS, NOSE, MANDIBLE 643185 Terminal Sacrifice Killed on Day : 91 Exposure Group : 90-DAY EXPOSURE Animal is signed off from necropsy Gross Pathology : 643185 No Macroscopic Abnormality Observed : LIVER, KIDNEYS, LUNGS, HEART, SKELETAL MUSCLE, SPLEEN, AORTA, BRAIN, SPINAL CORD, STOMACH, DUODENUM, JEJUNUM, ILEUM, PANCREAS, CECUM, COLON, RECTUM, MESENTERIC LYMPH NODE, SALIVARY GLANDS, MANDIBULAR LYMPH NODE, THYMUS, ADRENAL GLANDS, SCIATIC NERVE, PITUITARY GLAND, Continued on the next page .... 877 Company Sanitized. Does not contain T  -H-24516: Subchronic Toxicity : 90-Day Gavage Study in Rats with One-Generation Reproduction Evaluations INDIVIDUAL ANIMAL GROSS AND MICROSCOPIC OBSERVATIONS Dose Group : I - 0 mg/kg/day Sex: Males Animal Ref 643185 Microscopic & Macroscopic Findings Continued from previous page Gross Pathology : No Macroscopic Abnormality Observed : THYROID GLAND, PARATHYROID GLANDS, TRACHEA, ESOPHAGUS, PHARYNX/LARYNX, EYE(S) WITH OPTIC NERVE, SKIN, PROSTATE, SEMINAL VESICLES, URINARY BLADDER, TESTES, EPIDIDYMIDES, FEMUR/KNEE JOINT, STERNUM, NOSE, MANDIBLE Histopathology : LIVER : INFLAMMATION, SUBACUTE/CHRONIC, THYROID GLAND : ALTERATION, COLLOID, minimal. minimal. No Microscopic Abnormality Observed : KIDNEYS, LUNGS, HEART, SKELETAL MUSCLE, SPLEEN, AORTA, BRAIN, SPINAL CORD, STOMACH, DUODENUM, JEJUNUM. ILEUM, PANCREAS, CECUM, COLON, RECTUM, MESENTERIC LYMPH NODE, SALIVARY GLANDS, MANDIBULAR LYMPH NODE, THYMUS, ADRENAL GLANDS, SCIATIC NERVE. PITUITARY GLAND, PARATHYROID GLANDS. TRACHEA, ESOPHAGUS, PHARYNX/LARYNX, EYE(S) WITH OPTIC NERVE, SKIN, PROSTATE, SEMINAL VESICLES, URINARY BLADDER, TESTES, EPIDIDYMIDES, FEMUR/KNEE JOINT, STERNUM, BONE MARROW, NOSE, MANDIBLE 878. Company Sanitized. Does not contain ^ ^ H-24516: Subchronic Toxicity 90-Day Gavage Study in Rats with One-Generation Reproduction Evaluations INDIVIDUAL ANIMAL GROSS AND MICROSCOPIC OBSERVATIONS Dose Group : I - 0 mg/kg/day Sex: Males Animal Ref Microscopic & Macroscopic Findings 643189 Terminal Sacrifice Killed on Day : 91 Exposure Group : 90-DAY EXPOSURE Animal is signed off from necropsy Gross Pathology : No Macroscopic Abnormality Observed : LIVER, KIDNEYS, LUNGS, HEART, SKELETAL MUSCLE, SPLEEN, AORTA, BRAIN, SPINAL CORD, STOMACH, DUODENUM, JEJUNUM, ILEUM, PANCREAS, CECUM, COLON, RECTUM, MESENTERIC LYMPH NODE, SALIVARY GLANDS, MANDIBULAR LYMPH NODE, THYMUS, ADRENAL GLANDS, SCIATIC NERVE, PITUITARY GLAND, THYROID GLAND, PARATHYROID GLANDS, TRACHEA, ESOPHAGUS, - "PHARYNX/LARYNX, EYE(S) WITH OPTIC NERVE, SKIN, PROSTATE, SEMINAL VESICLES, URINARY BLADDER, TESTES, EPIDIDYMIDES, FEMUR/KNEE JOINT, STERNUM, NOSE, MANDIBLE Histopathology : . LIVER : INFLAMMATION, FATTY CHANGE, FATTY CHANGE, HEART : SUBACUTE/CHRONIC, minimal. CEMTRILOBULAR, minimal. MEDIAN CLEFT, minimal. CARDIOMYOPATHY, minimal. THYROID GLAND : ALTERATION, COLLOID, minimal. PARATHYROID GLANDS : NOT PRESENT. 643189 Continued on the next page .... 879 Company Sanitized. Does not contain T ,f.^;; H-24516: Subchronic Toxicity 90-Day Gavage Study in Rats with One-Generation Reproduction Evaluations INDIVIDUAL ANIMAL GROSS AND MICROSCOPIC OBSERVATIONS Dose Group : I - 0 mg/kg/day Sex: Males Animal Ref Microscopic & Macroscopic Findings 643189 Continued from previous page Histopathology No Microscopic Abnormality Observed : KIDNEYS, LUNGS, SKELETAL MUSCLE, SPLEEN, AORTA, BRAIN, SPINAL CORD, STOMACH, DUODENUM, JEJUNUM, ILEUM, PANCREAS, CECUM, COLON, RECTUM, MESENTERIC LYMPH NODE, SALIVARY GLANDS, MANDIBULAR LYMPH NODE, THYMUS, ADRENAL GLANDS, SCIATIC NERVE, PITUITARY GLAND, TRACHEA, ESOPHAGUS, PHARYNX/LARYNX. EYE(S) WITH OPTIC NERVE, SKIN, PROSTATE, SEMINAL VESICLES, URINARY BLADDER, TESTES, EPIDIDYMIDES, FEMUR/KNEE JOINT, STERNUM, BONE MARROW, NOSE, MANDIBLE 643195 ' Terminal Sacrifice Killed on Day : 125 Exposure Group : ONE-MONTH RECOVERY Animal is signed off from necropsy Gross Pathology No Macroscopic Abnormality Observed : LIVER, KIDNEYS, LUNGS, HEART, SKELETAL MUSCLE, SPLEEN, AORTA, BRAIN, SPINAL CORD, STOMACH, DUODENUM, JEJUNUM, ILEUM, PANCREAS, CECUM, COLON, RECTUM, MESENTERIC LYMPH NODE, SALIVARY GLANDS, MANDIBULAR LYMPH NODE, THYMUS, ADRENAL GLAMDS, SCIATIC NERVE, PITUITARY GLAND, THYROID GLAND, PARATHYROID GLANDS, TRACHEA, ESOPHAGUS, PHARYNX/LARYNX, EYE(S) WITH OPTIC NERVE, SKIN, PROSTATE, SEMINAL VESICLES, URINARY BLADDER, TESTES, EPIDIDYMIDES, FEMUR/KNEE JOINT, STERNUM, NOSE, MANDIBLE 643195 Continued on the next page 880 Company Sanitized. Does not contain TSC H-24516: Subchronic Toxicity 90-Day Gavage Study in Rats with One-Generation Reproduction Evaluations INDIVIDUAL ANIMAL GROSS AND MICROSCOPIC OBSERVATIONS Dose Group : I - 0 mg/kg/day .Sex: Males Animal Ref Microscopic & Macroscopic Findings 643195 Continued from previous page Histopathology : LIVER : INFLAMMATION, SUBACUTE/CHRONIC, minimal. KIDNEYS : NEPHROPATHY, CHRONIC PROGRESSIVE, minimal. THYROID GLAND : ALTERATION, COLLOID, minimal. No Microscopic Abnormality Observed : NOSE, MANDIBLE 643204 . Terminal Sacrifice Killed on Day : 91 . Exposure Group : 90-DAY EXPOSURE Animal is signed off from necropsy Gross Pathology : No Macroscopic Abnormality Observed : LIVER, KIDNEYS, LUNGS, HEART, SKELETAL MUSCLE, SPLEEN, AORTA, BRAIN, SPINAL CORD, STOMACH, DUODENUM, JEJUNUM, ILEUM, PANCREAS, CECUM, COLON, RECTUM, MESENTERIC LYMPH NODE, SALIVARY GLANDS, MANDIBULAR LYMPH MODE, THYMUS, ADRENAL GLANDS, SCIATIC NERVE, PITUITARY GLAND, THYROID GLAND, PARATHYROID GLANDS, TRACHEA, ESOPHAGUS, PHARYNX/LARYNX, EYE(S) WITH OPTIC NERVE, SKIN, PROSTATE, SEMINAL VESICLES, URINARY BLADDER, TESTES, EPIDIDYMIDES, FEMUR/KNEE JOINT, STERNUM, NOSE, MANDIBLE 643204 Continued on the next page .... 881 Company Sanitized. Does not contain ^. H-24516: Subchronic Toxicity 90-Day Gavage Study in Rats with One-Generation Reproduction Evaluations INDIVIDUAL ANIMAL GROSS AND MICROSCOPIC OBSERVATIONS Dose Group : I - 0 mg/kg/day Sex: Males Animal Ref Microscopic & Macroscopic Findings 643204 . Continued from previous page Histopathology : LIVER : INFLAMMATION, SUBACUTE/CHRONIC, minimal. KIDNEYS : NEPHROPATHY, CHRONIC PROGRESSIVE, minimal. LUNGS : INFLAMMATION, SUBACUTE/CHRONIC, minimal. HEART : CARDIOMYOPATHY, minimal. THYROID GLAND : ALTERATION, COLLOID, minimal. No Microscopic Abnormality Observed : SKELETAL MUSCLE, SPLEEN. AORTA, BRAIN, SPINAL CORD, STOMACH, DUODENUM, JEJUNUM, ILEUM, PANCREAS, CECUM, COLON, RECTUM, MESENTERIC LYMPH NODE, SALIVARY GLANDS, MANDIBULAR LYMPH NODE, THYMUS, ADRENAL GLANDS, SCIATIC NERVE, PITUITARY GLAND, PARATHYROID GLANDS. TRACHEA, ESOPHAGUS, PHARYNX/LARYNX, EYE(S) WITH OPTIC NERVE, SKIN, PROSTATE, SEMINAL VESICLES, URINARY BLADDER, TESTES, EPIDIDYMIDES, FEMUR/KNEE JOINT, STERNUM, BONE MARROW, NOSE, MANDIBLE 882 Company Sanitized. Does not contain H-24516: Subchronic Toxicity 90-Day Gavage Study in Rats with One-Generation Reproduction Evaluations INDIVIDUAL ANIMAL GROSS AND MICROSCOPIC OBSERVATIONS Dose Group : I - 0 mg/kg/day Sex: Males Animal Ref Microscopic & Macroscopic Findings 643205 Terminal Sacrifice Killed on Day : 91 Exposure Group : 90-DAY EXPOSURE Animal is signed off from necropsy Gross Pathology : No Macroscopic Abnormality Observed : LIVER, KIDNEYS, LUNGS, HEART, SKELETAL MUSCLE, SPLEEN, AORTA, BRAIN, SPIMAL CORD, STOMACH, DUODENUM, JEJUNUM, ILEUM, PANCREAS, CECUM, COLON, RECTUM, MESENTERIC LYMPH NODE, SALIVARY GLANDS, MANDIBULAR LYMPH NODE, THYMUS, ADRENAL GLANDS, SCIATIC NERVE, PITUITARY GLAND, THYROID GLAND, PARATHYROID GLANDS, TRACHEA, ESOPHAGUS, - PHARYNX/LARYNX, EYE(S) WITH OPTIC NERVE, SKIN, PROSTATE, SEMINAL VESICLES, URINARY BLADDER, TESTES, EPIDIDYMIDES, FEMUR/KNEE JOINT, STERNUM, NOSE, MANDIBLE Histopathology : LIVER : INFLAMMATION, SUBACUTE/CHRONIC, LUNGS : INFLAMMATION, SUBACUTE/CHRONIC, HEART : CARDIOMYOPATHY, minimal. THYROID GLAND : ALTERATION, COLLOID, minimal. EYE(S) WITH OPTIC NERVE : FOLD/ROSETTE. RETINAL, minimal. minimal. minimal. 643205 Continued on the next page .... 883 Company Sanitized. Does not contain H-24516: Subchronic Toxicity 90-Day Gavage Study in Rats with One-Generation Reproduction Evaluations INDIVIDUAL ANIMAL GROSS AND MICROSCOPIC OBSERVATIONS Dose Group : I - 0 mg/kg/day Sex: Males Animal Ref Microscopic & Macroscopic Findings 643205 Continued from previous page Histopathology : No Microscopic Abnormality Observed : KIDNEYS, SKELETAL MUSCLE, SPLEEN, AORTA, BRAIN, SPINAL CORD, STOMACH, DUODENUM, JEJUNUM, ILEUM, PANCREAS, CECUM, COLON, RECTUM, MESENTERIC LYMPH NODE, SALIVARY GLANDS, MANDIBULAR LYMPH NODE, THYMUS, ADRENAL GLANDS, SCIATIC NERVE, PITUITARY GLAND, PARATHYROID GLANDS, TRACHEA, ESOPHAGUS, PHARYNX/LARYNX, SKIN, PROSTATE, SEMINAL VESICLES, URINARY BLADDER, TESTES. EPIDIDYMIDES, FEMUR/KNEE JOINT, STERNUM, BONE MARROW, NOSE, MANDIBLE 643210 - Terminal Sacrifice Killed on Day : 181 Exposure Group : THREE-MONTH RECOVERY Animal is signed off from necropsy Gross Pathology : No Macroscopic Abnormality Observed : LIVER, KIDNEYS, LUNGS. HEART, SKELETAL MUSCLE, SPLEEN, AORTA, BRAIN, SPINAL CORD, STOMACH, DUODENUM, JEJUNUM, ILEUM, PANCREAS, CECUM, COLON, RECTUM, MESENTERIC LYMPH NODE, SALIVARY GLANDS, MANDIBULAR LYMPH NODE, THYMUS, ADRENAL GLANDS, SCIATIC NERVE, PITUITARY GLAND, THYROID GLAND, PARATHYROID GLANDS, TRACHEA, ESOPHAGUS, PHARYNX/LARYNX, EYE(S) WITH OPTIC NERVE, SKIN, PROSTATE, SEMINAL VESICLES, URINARY BLADDER, TESTES, EPIDIDYMIDES, FEMUR/KNEE JOINT, STERNUM, NOSE, MANDIBLE 643210 Continued on the next page .... 884 Company Sanitized. Does not contain  H-24516: Subchronic Toxicity 90-Day Gavage Study in Rats with One-Generation Reproduction Evaluations INDIVIDUAL ANIMAL GROSS AMD MICROSCOPIC OBSERVATIONS Dose Group : I - 0 ing/kg/day Sex: Males Animal Ref 643210 . Microscopic & Macroscopic Findings Continued from previous page Histopathology : LIVER : INFLAMMATION, SUBACUTE/CHRONIC, NECROSIS, FOCAL, minimal. KIDNEYS : minimal. NEPHROPATHY, CHRONIC PROGRESSIVE, minimal. THYROID GLAND : ALTERATION, COLLOID, mild. No Microscopic Abnormality Observed : NOSE 643226 Terminal Sacrifice Killed on Day : 125 Exposure Group : ONE-MONTH RECOVERY Animal, is signed off from necropsy Gross Pathology : TESTES : DEFORMITY, RIGHT. EPIDIDYMIDES : SMALL, RIGHT. 643226 No Macroscopic Abnormality Observed : LIVER, KIDNEYS, LUNGS, HEART, SKELETAL MUSCLE, SPLEEN, AORTA, BRAIN, SPINAL CORD, STOMACH, DUODENUM, JEJUNUM, ILEUM, PANCREAS. CECUM, COLON, RECTUM, MESENTERIC LYMPH NODE, SALIVARY GLANDS, MANDIBULAR LYMPH NODE, THYMUS, ADRENAL GLANDS, SCIATIC NERVE, PITUITARY GLAND, Continued on the next page .... 885 Company Sanitized. Does not contain ' H H-24516: Subchronic Toxicity 90-Day Gavage Study in Rats with One-Generation Reproduction Evaluations INDIVIDUAL ANIMAL GROSS AND MICROSCOPIC OBSERVATIONS Dose Group : I - 0 mg/kg/day Sex: Males Animal Ref Microscopic & Macroscopic Findings 643226 Continued from previous page Gross Pathology : No Macroscopic Abnormality Observed : THYROID GLAND, PARATHYROID GLANDS, TRACHEA, ESOPHAGUS, PHARYNX/LARYNX, EYE(S) WITH OPTIC NERVE, SKIN, PROSTATE, SEMINAL VESICLES, URINARY BLADDER, FEMUR/KNEE JOINT, STERNUM, NOSE, MANDIBLE Histopathology : LIVER : INFLAMMATION, SUBACUTE/CHRONIC, minimal. KIDNEYS : NEPHROPATHY, CHRONIC PROGRESSIVE, minimal. THYROID GLAND : ALTERATION, COLLOID, mild. TESTES : DEGENERATION/ATROPHY, SEMINIFEROUS TUBULES, mild. UNILATERAL, No Microscopic Abnormality Observed : EPIDIDYMIDES, NOSE, MANDIBLE 886 Company Sanitized. Does not co H-24516: Subchronic Toxicity 90-Day Gavage Study in Rats with One-Generation Reproduction Evaluations INDIVIDUAL ANIMAL GROSS AND MICROSCOPIC OBSERVATIONS Dose Group : I - 0 mg/kg/day Sex: Males Animal Ref Microscopic & Macroscopic Findings 643232 Terminal Sacrifice Killed on Day : 181 Exposure Group : THREE-MONTH RECOVERY Animal is signed off from necropsy Gross Pathology : No Macroscopic Abnormality Observed : LIVER, KIDNEYS, LUNGS, HEART, SKELETAL MUSCLE, SPLEEN, AORTA, BRAIN, SPINAL CORD, STOMACH, DUODENUM, JEJUNUM, ILEUM, PANCREAS, CECUM, COLON, RECTUM, MESENTERIC LYMPH NODE, SALIVARY GLANDS, MANDIBULAR LYMPH NODE, THYMUS, ADRENAL GLANDS, SCIATIC NERVE, PITUITARY GLAND, THYROID GLAND, PARATHYROID GLANDS, TRACHEA, ESOPHAGUS, PHARYNX/LARYNX, EYE(S) WITH OPTIC NERVE, SKIN, PROSTATE, SEMINAL VESICLES, URINARY BLADDER, TESTES, EPIDIDYMIDES. FEMUR/KNEE JOINT, STERNUM, NOSE, MANDIBLE Histopathology : LIVER : INFLAMMATION, SUBACUTE/CHRONIC, minimal. FATTY CHANGE, CENTRILOBULAR, mild. THYROID GLAND : ALTERATION, COLLOID, minimal. No Microscopic Abnormality Observed : KIDNEYS, NOSE 887 Company Sanitized. Does not contain T H-24516: Subchronic Toxicity 90-Day Gavage Study in Rats with One-Generation Reproduction Evaluations INDIVIDUAL ANIMAL GROSS AND MICROSCOPIC OBSERVATIONS Dose Group : I - 0 mg/kg/day Sex: Males Animal Ref 643235 Microscopic & Macroscopic Findings Terminal Sacrifice Killed on Day : 91 Exposure Group : 90-DAY EXPOSURE Animal is signed off from necropsy Gross Pathology : No Macroscopic Abnormality Observed : LIVER, KIDNEYS, LUNGS, HEART, SKELETAL MUSCLE, SPLEEN, AORTA, BRAIN, SPINAL CORD, STOMACH, DUODENUM, JEJUNUM, ILEUM, PANCREAS, CECUM, COLON, RECTUM, MESENTERIC LYMPH NODE, SALIVARY GLANDS, MANDIBULAR LYMPH NODE, THYMUS, ADRENAL GLANDS, SCIATIC NERVE, PITUITARY GLAND, THYROID GLAND, PARATHYROID GLANDS, TRACHEA, ESOPHAGUS, - PHARYNX/LARYNX, EYE(S) WITH OPTIC NERVE, SKIN, PROSTATE, SEMINAL VESICLES, URINARY BLADDER, TESTES, EPIDIDYMIDES, FEMUR/KNEE JOINT, STERNUM, NOSE, MANDIBLE Histopathology : LIVER : INFLAMMATION, SUBACUTE/CHRONIC, HEART : CARDIOMYOPATHY, minimal. THYROID GLAND : INFLAMMATION, SUBACUTE/CHRONIC, ALTERATION, COLLOID, minimal. minimal. minimal. 643235 Continued on the next page .... 888 Company Sanitized. Does not contain TSC H-24516: Subchronic Toxicity 90-Day Gavage Study in Rats with One-Generation Reproduction Evaluations INDIVIDUAL ANIMAL GROSS AND MICROSCOPIC OBSERVATIONS Dose Group : I - 0 mg/kg/day Sex: Males Animal Ref Microscopic & Macroscopic Findings 643235 Continued from previous page Histopathology : No Microscopic Abnormality Observed : KIDNEYS, LUNGS, SKELETAL MUSCLE, SPLEEN, AORTA, BRAIN, SPINAL CORD, STOMACH, DUODENUM, JEJUNUM, ILEUM, PANCREAS, CECUM, COLON, RECTUM, MESENTERIC LYMPH NODE, SALIVARY GLANDS, MANDIBULAR LYMPH NODE, THYMUS, ADRENAL GLANDS, SCIATIC NERVE, PITUITARY GLAND, PARATHYROID GLANDS, TRACHEA, ESOPHAGUS, PHARYNX/LARYNX, EYE(S) WITH OPTIC NERVE, SKIN, PROSTATE, SEMINAL VESICLES, URINARY BLADDER, TESTES, EPIDIDYMIDES, FEMUR/KNEE JOINT, STERNUM, BONE MARROW, NOSE, MANDIBLE 643237 Terminal Sacrifice Killed on Day : 125 Exposure Group : ONE-MONTH RECOVERY Animal i's signed off from necropsy Gross Pathology : 643237 No Macroscopic Abnormality Observed : LIVER, KIDNEYS, LUNGS, HEART, SKELETAL MUSCLE, SPLEEN, AORTA, BRAIN, SPINAL CORD, STOMACH, DUODENUM, JEJUNUM, ILEUM, PANCREAS, CECUM, COLON, RECTUM, MESENTERIC LYMPH NODE, SALIVARY GLANDS, MANDIBULAR LYMPH NODE, THYMUS, ADRENAL GLANDS, SCIATIC NERVE, PITUITARY GLAND, THYROID GLAND, PARATHYROID GLANDS, TRACHEA, ESOPHAGUS, PHARYNX/LARYNX, EYE(S) WITH OPTIC NERVE, SKIN, PROSTATE, SEMINAL VESICLES, URINARY BLADDER, TESTES, EPIDIDYMIDES, FEMUR/KNEE JOINT, STERNUM, NOSE, MANDIBLE Continued on the next page .... 889 Company Sanitized. Does not contain TS ^ H-24516: Subchronic Toxicity 90-Day Gavage Study in Rats with One-Generation Reproduction Evaluations INDIVIDUAL ANIMAL GROSS AMD MICROSCOPIC OBSERVATIONS Dose Group : I - 0 mg/kg/day Sex: Males Animal Ref 643237 Microscopic & Macroscopic Findings Continued from previous page Histopathology : LIVER : INFLAMMATION, SUBACUTE/CHRONIC, minimal. KIDNEYS : NEPHROPATHY, CHRONIC PROGRESSIVE, minimal. THYROID GLAND : ALTERATION, COLLOID, minimal. No Microscopic Abnormality Observed : NOSE, MANDIBLE 643241 "Terminal Sacrifice Killed on Day : .91 Exposure Group : 90-DAY EXPOSURE Animal is signed off from necropsy Gross Pathology : No Macroscopic Abnormality Observed : LIVER, KIDNEYS, LUNGS, HEART, SKELETAL MUSCLE, SPLEEN, AORTA, BRAIN, SPINAL CORD, STOMACH, DUODENUM, JEJUNUM, ILEUM, PANCREAS, CECUM, COLON, RECTUM, MESENTERIC LYMPH NODE, SALIVARY GLANDS, MANDIBULAR LYMPH NODE, THYMUS, ADRENAL GLANDS, SCIATIC NERVE, PITUITARY GLAND, THYROID GLAND, PARATHYROID GLANDS, TRACHEA, ESOPHAGUS, PHARYNX/LARYNX, EYE(S) WITH OPTIC NERVE, SKIN, PROSTATE, SEMINAL VESICLES, URINARY BLADDER, TESTES, EPIDIDYMIDES, FEMUR/KNEE JOINT, STERNUM, NOSE, MANDIBLE 643241 Continued on the next page .... 890 Company Sanitized. Does not contain  H-24516: Subchronic Toxicity 90-Day Gavage Study in Rats with One-Generation Reproduction Evaluations INDIVIDUAL AMIMAL GROSS AND MICROSCOPIC OBSERVATIONS Dose Group : I - 0 mg/kg/day Sex: Males Animal Ref Microscopic & Macroscopic Findings 643241 . Continued from previous page Histopathology : LIVER : INFLAMMATION, SUBACUTE/CHRONIC, minimal. KIDNEYS : NEPHROPATHY, CHRONIC PROGRESSIVE, minimal. PANCREAS : INFLAMMATION, SUBACUTE/CHRONIC, ATROPHY, minimal. THYROID GLAND : minimal. ALTERATION, COLLOID, minimal. No Microscopic Abnormality Observed : LUNGS, HEART, SKELETAL MUSCLE, SPLEEN, AORTA, BRAIN, SPINAL CORD, STOMACH, DUODENUM, JEJUNUM, ILEUM, CECUM, COLON, RECTUM, MESENTERIC LYMPH NODE, SALIVARY GLANDS, MANDIBULAR LYMPH NODE, THYMUS, ADRENAL GLANDS, SCIATIC NERVE, PITUITARY GLAND, PARATHYROID GLANDS, TRACHEA, ESOPHAGUS, PHARYNX/LARYNX, EYE(S) WITH OPTIC NERVE, SKIN, PROSTATE, SEMINAL VESICLES, URINARY BLADDER, TESTES, EPIDIDYMIDES, FEMUR/KNEE JOINT, STERNUM, BONE MARROW, NOSE, MANDIBLE 891 Company Sanitized. Does not contain TSC H-24516: Subchronic Toxicity 90-Day Gavage Study in Rats with One-Generation Reproduction Evaluations INDIVIDUAL ANIMAL GROSS AND MICROSCOPIC OBSERVATIONS Dose Group : I - 0 mg/kg/day Sex: Males Animal Ref Microscopic & Macroscopic Findings 643246 Terminal Sacrifice Killed on Day : 125 Exposure Group : ONE-MONTH RECOVERY Animal is signed off from necropsy Gross Pathology : No Macroscopic Abnormality Observed : LIVER, KIDNEYS, LUNGS, HEART, SKELETAL MUSCLE, SPLEEN, AORTA, BRAIN, SPINAL CORD, STOMACH, DUODENUM, JEJUNUM, ILEUM, PANCREAS, CECUM, COLON, RECTUM, MESENTERIC LYMPH NODE, SALIVARY GLANDS, MANDIBULAR LYMPH NODE, THYMUS, ADRENAL GLANDS, SCIATIC NERVE, PITUITARY GLAND, THYROID GLAND, PARATHYROID GLANDS, TRACHEA, ESOPHAGUS, PHARYNX/LARYNX, EYE(S) WITH OPTIC NERVE, SKIN, PROSTATE, SEMINAL VESICLES, URINARY BLADDER, TESTES, EPIDIDYMIDES, FEMUR/KNEE JOINT, STERNUM. NOSE, MANDIBLE Histopathology : LIVER : INFLAMMATION, SUBACUTE/CHRONIC, minimal. FATTY CHANGE, CENTRILOBULAR, minimal. KIDNEYS : NEPHROPATHY, CHRONIC PROGRESSIVE, minimal. THYROID GLAND : ALTERATION, COLLOID, minimal. No Microscopic Abnormality Observed : NOSE, MANDIBLE 892 Company Sanitized. Does not contain T ^ n H-24516: Subchronic Toxicity 90-Day Gavage Study in Rats with One-Generation Reproduction Evaluations INDIVIDUAL ANIMAL GROSS AND MICROSCOPIC OBSERVATIONS Dose Group : I - 0 ing/kg/day Sex: Males Animal Ref Microscopic & Macroscopic Findings 643253 Terminal Sacrifice Killed on Day : 125 Exposure Group : ONE-MONTH RECOVERY Animal is signed off from necropsy Gross Pathology : TESTES : SMALL, LEFT. EPIDIDYMIDES : SMALL, LEFT. No Macroscopic Abnormality Observed : -LIVER, KIDNEYS, LUNGS, HEART, SKELETAL MUSCLE, SPLEEN, - AORTA, BRAIN, SPINAL CORD, STOMACH, DUODENUM, JEJUNUM, ILEUM, PANCREAS, CECUM, COLON, RECTUM, MESENTERIC LYMPH NODE, SALIVARY GLANDS, MANDIBULAR LYMPH NODE, THYMUS, ADRENAL.GLANDS, SCIATIC NERVE, PITUITARY GLAND, THYROID GLAND, PARATHYROID GLANDS, TRACHEA, ESOPHAGUS, PHARYNX/LARYNX, EYE(S) WITH OPTIC NERVE, SKIN, PROSTATE, SEMINAL VESICLES, URINARY BLADDER, FEMUR/KNEE JOINT, STERNUM, NOSE, MANDIBLE Histopathology : , 643253 LIVER : INFLAMMATION, SUBACUTE/CHRONIC, minimal. FATTY CHANGE, MEDIAN CLEFT, minimal. KIDNEYS : NEPHROPATHY, CHRONIC PROGRESSIVE, minimal. THYROID GLAND : ALTERATION, COLLOID, minimal. Continued on the next page .... 893 Company Sanitized. Does not con H-24516: Subchronic Toxicity 90-Day Gavage Study in Rats with One-Generation Reproduction Evaluations INDIVIDUAL ANIMAL GROSS AND MICROSCOPIC OBSERVATIONS Dose Group : I - 0 mg/kg/day Sex: Males Animal Ref Microscopic & Macroscopic Findings 643253 Continued from previous page Histopathology : TESTES : DEGENERATION/ATROPHY, SEMINIFEROUS TUBULES, UNILATERAL, severe. EPIDIDYMIDES : OLIGOSPERMIA/GERM CELL DEBRIS, UNILATERAL, severe. No Microscopic Abnormality Observed : NOSE, MANDIBLE 643262 Terminal Sacrifice "Killed on Day : 125 Exposure Group : ONE-MONTH RECOVERY Animal is signed off from necropsy Gross Pathology : No Macroscopic Abnormality Observed : LIVER, KIDNEYS, LUNGS, HEART, SKELETAL MUSCLE, SPLEEN, AORTA, BRAIN, SPINAL CORD, STOMACH, DUODENUM, JEJUNUM, ILEUM, PANCREAS, CECUM, COLON, RECTUM, MESENTERIC LYMPH NODE, SALIVARY GLANDS, MANDIBULAR LYMPH NODE, THYMUS, ADRENAL GLANDS, SCIATIC NERVE, PITUITARY GLAND, THYROID GLAND, PARATHYROID GLANDS, TRACHEA, ESOPHAGUS, PHARYNX/LARYNX, EYE(S) WITH OPTIC NERVE, SKIN, PROSTATE, SEMINAL VESICLES, URINARY BLADDER, TESTES, EPIDIDYMIDES, FEMUR/KNEE JOINT, STERNUM, NOSE, MANDIBLE 643262 Continued on the next page .... 894 Company Sanitized. Does not cont  H-24516: Subchronic Toxicity 90-Day Gavage Study in Rats with One-Generation Reproduction Evaluations INDIVIDUAL ANIMAL GROSS AND MICROSCOPIC OBSERVATIONS Dose Group : I-- 0 mg/kg/day Sex: Males Animal Ref Microscopic & Macroscopic Findings 643262 Continued from previous page Histopathology : LIVER : INFLAMMATION, SUBACUTE/CHRONIC, THYROID GLAND : ALTERATION, COLLOID, minimal. minimal. No Microscopic Abnormality Observed : KIDNEYS, NOSE, MANDIBLE 643265 Terminal Sacrifice Killed on Day : 181 " Exposure Group : THREE-MONTH RECOVERY Animal is signed off.from necropsy Gross Pathology : No Macroscopic Abnormality Observed : LIVER, KIDNEYS, LUNGS, HEART, SKELETAL MUSCLE, SPLEEN, AORTA, BRAIN, SPINAL CORD, STOMACH, DUODENUM, JEJUNUM, ILEUM, PANCREAS, CECUM, COLON, RECTUM, MESENTERIC LYMPH NODE, SALIVARY GLANDS, MANDIBULAR LYMPH NODE, THYMUS, ADRENAL GLANDS, SCIATIC NERVE, PITUITARY GLAND, THYROID GLAND, PARATHYROID GLANDS, TRACHEA, ESOPHAGUS, PHARYNX/LARYNX, EYE(S) WITH OPTIC NERVE, SKIN, PROSTATE, SEMINAL VESICLES, URINARY BLADDER, TESTES, EPIDIDYMIDES, FEMUR/KNEE JOINT, STERNUM, NOSE, MANDIBLE 643265 Continued on the next page .... 895 Company Sanitized. Does not contain TS  H-24516: Subchronic Toxicity II 90-Day Gavage Study in Rats with One-Generation Reproduction Evaluations INDIVIDUAL ANIMAL GROSS AND MICROSCOPIC OBSERVATIONS Dose Group : I - 0 ing/kg/day Sex: Males Animal Ref Microscopic & Macroscopic Findings ; 643265 Continued from previous page Histopathology : LIVER ; INFLAMMATION, SUBACUTE/CHRONIC, THYROID GLAND : ALTERATION, COLLOID, moderate. minimal. No Microscopic Abnormality Observed : KIDNEYS, NOSE 643268 Terminal Sacrifice Killed on Day : 181 Exposure Group : THREE-MONTH RECOVERY Animal is signed off from necropsy Gross Pathology : No Macroscopic Abnormality Observed : LIVER, KIDNEYS, LUNGS, HEART, SKELETAL MUSCLE, SPLEEN, AORTA, BRAIN, SPINAL CORD, STOMACH, DUODENUM, JEJUNUM, ILEUM, PANCREAS, CECUM, COLON, RECTUM, MESENTERIC LYMPH NODE, SALIVARY GLANDS, MANDIBULAR LYMPH NODE, THYMUS, ADRENAL GLANDS, SCIATIC NERVE, PITUITARY GLAND, THYROID GLAND, PARATHYROID GLANDS, TRACHEA, ESOPHAGUS, PHARYNX/LARYNX, EYE(S) WITH OPTIC NERVE, SKIN, PROSTATE, SEMINAL VESICLES, URINARY BLADDER, TESTES, EPIDIDYMIDES. FEMUR/KNEE JOINT, STERNUM, NOSE, MANDIBLE 643268 Continued on the next page .... 896 Company Sanitized. Does not contain ^, ^ H-24516: Subchronic Toxicity 90-Day Gavage Study in Rats with One-Generation Reproduction Evaluations INDIVIDUAL ANIMAL GROSS AND MICROSCOPIC OBSERVATIONS Dose Group : I - 0 mg/kg/day Sex: Males Animal Ref Microscopic & Macroscopic Findings 643268 Continued from previous page Histopathology : 643288 LIVER : INFLAMMATION, KIDNEYS : SUBACUTE/CHRONIC, minimal. NEPHROPATHY, CHRONIC PROGRESSIVE, minimal. THYROID GLAND : ALTERATION, COLLOID, minimal. NOSE : INFLAMMATION, SUBACUTE/CHRONIC, mild. HYPERPLASIA/SQUAMOUS METAPLASIA, RESPIRATORY, mild. EPITHELIUM, Terminal Sacrifice Killed on Day : 91 Exposure Group : 90-DAY EXPOSURE Animal is signed off from necropsy Gross Pathology : : 643288 No Macroscopic Abnormality Observed : LIVER, KIDNEYS, LUNGS, HEART, SKELETAL MUSCLE, SPLEEN, AORTA, BRAIN, SPINAL CORD, STOMACH, DUODENUM, JEJUNUM, ILEUM, PANCREAS, CECUM, COLON, RECTUM, MESENTERIC LYMPH NODE, SALIVARY GLANDS, MANDIBULAR LYMPH NODE, THYMUS, ADRENAL GLANDS, SCIATIC NERVE, PITUITARY GLAND, THYROID GLAND, PARATHYROID GLANDS, TRACHEA, ESOPHAGUS, PHARYNX/LARYNX, EYE(S) WITH OPTIC NERVE, SKIN, PROSTATE; SEMINAL VESICLES, URINARY BLADDER, TESTES, EPIDIDYMIDES, FEMUR/KNEE JOINT, STERNUM, NOSE, MANDIBLE Continued on the next page .... 897 Company Sanitized. Does not contain  H-24516: Subchronic Toxicity 90-Day Gavage Study in Rats with One-Generation Reproduction Evaluations INDIVIDUAL ANIMAL GROSS AND MICROSCOPIC OBSERVATIONS Dose Group : I - 0 mg/kg/day Sex: Males Animal Ref Microscopic & Macroscopic Findings 643288 Continued from previous page Histopathology : LIVER : INFLAMMATION, SUBACUTE/CHRONIC, PANCREAS : INFLAMMATION, SUBACUTE/CHRONIC, THYROID GLAND : ALTERATION, COLLOID, minimal. PARATHYROID GLANDS : NOT PRESENT. PROSTATE : INFLAMMATION, SUBACUTE/CHRONIC, minimal. minimal. minimal. No Microscopic Abnormality Observed : KIDNEYS, LUNGS, HEART. SKELETAL MUSCLE, SPLEEN, AORTA, BRAIN, SPINAL CORD, STOMACH, DUODENUM, JEJUNUM, ILEUM, CECUM,,COLON, RECTUM, MESENTERIC LYMPH NODE, SALIVARY GLANDS, MANDIBULAR LYMPH NODE, THYMUS, ADRENAL GLANDS, SCIATIC NERVE, PITUITARY GLAND, TRACHEA, ESOPHAGUS, PHARYNX/LARYNX, EYE(S) WITH OPTIC NERVE, SKIN, SEMINAL VESICLES, URINARY BLADDER, TESTES, EPIDIDYMIDES, FEMUR/KNEE JOINT, STERNUM, BONE MARROW, NOSE, MANDIBLE 898 Company Sanitized. Does not contain T H-24516: Subchronic Toxicity 90-Day Gavage Study in Rats with One-Generation Reproduction Evaluations INDIVIDUAL ANIMAL GROSS AND MICROSCOPIC OBSERVATIONS Dose Group : I - 0 mg/kg/day Sex: Males Animal Ref Microscopic & Macroscopic Findings 643300 . Terminal Sacrifice Killed on Day : 91 Exposure Group : 90-DAY EXPOSURE Animal is signed off from necropsy Gross Pathology : No Macroscopic Abnormality Observed : LIVER, KIDNEYS, LUNGS, HEART, SKELETAL MUSCLE. SPLEEN, AORTA, BRAIN, SPINAL CORD, STOMACH, DUODENUM, JEJUNUM, ILEUM, PANCREAS, CECUM, COLON, RECTUM, MESENTERIC LYMPH NODE, SALIVARY GLANDS, MANDIBULAR LYMPH NODE, THYMUS, ADRENAL GLANDS, SCIATIC NERVE, PITUITARY GLAND, THYROID GLAND, PARATHYROID GLANDS, TRACHEA, ESOPHAGUS, . PHARYNX/LARYNX, EYE(S) WITH OPTIC NERVE, SKIN, PROSTATE, SEMINAL VESICLES, URINARY BLADDER, TESTES, EPIDIDYMIDES, FEMUR/KNEE JOINT, STERNUM, NOSE, MANDIBLE Histopathology : LIVER : INFLAMMATION, SUBACUTE/CHRONIC, minimal. FATTY CHANGE, MEDIAN CLEFT, minimal. KIDNEYS : NEPHROPATHY, CHRONIC PROGRESSIVE, minimal. HEART : CARDIOMYOPATHY, minimal. PANCREAS : ATROPHY, minimal. THYROID GLAND : ALTERATION, COLLOID, minimal. 643300 Continued on the next page .... 899 Company Sanitized. Does not contain T H-24516: Subchronic Toxicity 90-Day Gavage Study in Rats with One-Generation Reproduction Evaluations INDIVIDUAL ANIMAL GROSS AND MICROSCOPIC OBSERVATIONS Dose Group : I - 0 mg/kg/day Sex: Males Animal Ref 643300 Microscopic & Macroscopic Findings Continued from previous page Histopathology : No Microscopic Abnormality Observed : LUNGS, SKELETAL MUSCLE, SPLEEN, AORTA, BRAIN. SPINAL CORD, STOMACH, DUODENUM, JEJUNUM, ILEUM, CECUM, COLON, RECTUM, MESENTERIC LYMPH NODE, SALIVARY GLANDS, MANDIBULAR LYMPH NODE, THYMUS, ADRENAL GLANDS, SCIATIC NERVE, PITUITARY GLAND, PARATHYROID GLANDS, TRACHEA, ESOPHAGUS, PHARYNX/LARYNX, EYE(S) WITH OPTIC NERVE, SKIN, PROSTATE, SEMINAL VESICLES, URINARY BLADDER, TESTES, EPIDIDYMIDES, FEMUR/KNEE JOINT, STERNUM, BONE MARROW, NOSE, MANDIBLE 643303 - Terminal Sacrifice Killed on Day : 125 Exposure Group : ONE-MONTH RECOVERY Animal is signed off from necropsy Gross Pathology : No Macroscopic Abnormality Observed : LIVER, KIDNEYS, LUNGS, HEART, SKELETAL MUSCLE, SPLEEN, AORTA, BRAIN, SPINAL CORD, STOMACH, DUODENUM, JEJUNUM, ILEUM, PANCREAS, CECUM, COLON, RECTUM, MESENTERIC LYMPH NODE, SALIVARY GLANDS, MANDIBULAR LYMPH NODE, THYMUS, ADRENAL GLANDS, SCIATIC NERVE, PITUITARY GLAND, THYROID GLAND, PARATHYROID GLANDS, TRACHEA, ESOPHAGUS, PHARYNX/LARYNX, EYE(S) WITH OPTIC NERVE, SKIN, PROSTATE, SEMINAL VESICLES, URINARY BLADDER, TESTES, EPIDIDYMIDES, FEMUR/KNEE JOINT, STERNUM, NOSE, MANDIBLE 643303 Continued on the next page .... 900 Company Sanitized. Does not conta /f" H-24516: Subchronic Toxicity 90-Day Gavage Study in Rats with One-Generation Reproduction Evaluations INDIVIDUAL ANIMAL GROSS AND MICROSCOPIC OBSERVATIONS Dose Group : I - 0 ing/kg/day Sex: Males Animal Ref Microscopic & Macroscopic Findings 643303 Continued from previous page Histopathology : LIVER : INFLAMMATION, SUBACUTE/CHRONIC, THYROID GLAND : ALTERATION, COLLOID, minimal. minimal, No Microscopic Abnormality Observed : KIDNEYS, NOSE, MANDIBLE 643304 Terminal Sacrifice Killed on Day : 125 . "Exposure Group : ONE-MONTH RECOVERY Animal is signed off from necropsy Gross Pathology : SPLEEN : DEFORMITY. MAMDIBULAR LYMPH NODE : DISCOLORATION, RED. THYMUS : SMALL. 643304 Continued on the next page .... 901 Company Sanitized. Does not contain ^ 1 H-24516: Subchronic Toxicity 90-Day Gavage Study in Rats with One-Generation Reproduction Evaluations INDIVIDUAL ANIMAL GROSS AMD MICROSCOPIC OBSERVATIONS Dose Group : I - 0 ing/kg/day Sex: Males Animal Ref Microscopic & Macroscopic Findings 643304 . Continued from previous page Gross Pathology : No Macroscopic Abnormality Observed : LIVER, KIDNEYS, LUNGS, HEART, SKELETAL MUSCLE, AORTA, BRAIN, SPINAL CORD, STOMACH, DUODENUM, JEJUNUM, ILEUM, PANCREAS, CECUM, COLON, RECTUM, MESENTERIC LYMPH NODE, SALIVARY GLANDS, ADRENAL GLANDS, SCIATIC NERVE, PITUITARY GLAND, THYROID GLAND, PARATHYROID GLANDS, TRACHEA, ESOPHAGUS, PHARYNX/LARYNX, EYE(S) WITH OPTIC NERVE, SKIN, PROSTATE, SEMINAL VESICLES, URINARY BLADDER, TESTES, EPIDIDYMIDES, FEMUR/KNEE JOINT, STERNUM, NOSE, MANDIBLE Histopathology : LIVER : INFLAMMATION, SUBACUTE/CHRONIC, minimal. MANDIBULAR LYMPH NODE : ERYTHROCYTOSIS/ERYTHROPHAGOCYTOSIS, SINUS, THYROID GLAMD : ALTERATION, COLLOID, minimal. mild. No Microscopic Abnormality Observed : KIDNEYS, SPLEEN, THYMUS, NOSE, MANDIBLE 902 Company Sanitized. Does not contain  H-24516: Subchronic Toxicity 90-Day Gavage Study in Rats with One-Generation Reproduction Evaluations INDIVIDUAL ANIMAL GROSS AND MICROSCOPIC OBSERVATIONS Dose Group : Animal Ref III - 25 mg/kg/day Sex: Males Microscopic & Macroscopic Findings 643173 . Terminal Sacrifice Killed on Day : 91 Exposure Group : 90-DAY EXPOSURE Animal is signed off from necropsy Gross Pathology : No Macroscopic Abnormality Observed : LIVER, KIDNEYS, LUNGS, HEART, SKELETAL MUSCLE, SPLEEN, AORTA, BRAIN, SPINAL CORD, STOMACH, DUODENUM, JEJUNUM, ILEUM, PANCREAS, CECUM, COLON, RECTUM. MESENTERIC LYMPH NODE, SALIVARY GLANDS, MANDIBULAR LYMPH NODE, THYMUS, ADRENAL GLANDS, SCIATIC NERVE, PITUITARY GLAND, THYROID GLAND, PARATHYROID GLANDS, TRACHEA, ESOPHAGUS, " "PHARYNX/LARYNX, EYE(S) WITH OPTIC NERVE, SKIN, PROSTATE, SEMINAL VESICLES, URINARY BLADDER, TESTES, EPIDIDYMIDES, FEMUR/KNEE JOINT, STERNUM, NOSE, MANDIBLE Histopathology : LIVER : INFLAMMATION, SUBACUTE/CHRONIC, THYROID GLAND : ALTERATION, COLLOID, minimal. minimal. No Microscopic Abnormality Observed : KIDNEYS, NOSE, MANDIBLE 903 Company Sanitized. Does not co  H-24516: Subchronic Toxicity 90-Day Gavage Study in Rats with One-Generation Reproduction Evaluations INDIVIDUAL ANIMAL GROSS AND MICROSCOPIC OBSERVATIONS Dose Group : III - 25 nig/kg/day Sex: Males Animal Ref Microscopic & Macroscopic Findings 643179 Terminal Sacrifice Killed on Day : 91 Exposure Group : 90-DAY EXPOSURE Animal is signed off from necropsy Gross Pathology : No Macroscopic Abnormality Observed : LIVER, KIDNEYS, LUNGS, HEART, SKELETAL MUSCLE, SPLEEN, AORTA, BRAIM, SPINAL CORD, STOMACH, DUODENUM, JEJUNUM, ILEUM, PANCREAS, CECUM, COLON, RECTUM, MESENTERIC LYMPH NODE, SALIVARY GLANDS, MAMDIBULAR LYMPH NODE, THYMUS, ADRENAL GLANDS, SCIATIC NERVE, PITUITARY GLAND, THYROID GLAND, PARATHYROID GLANDS, TRACHEA, ESOPHAGUS, -PHARYNX/LARYNX, EYE(S) WITH OPTIC NERVE, SKIN, PROSTATE, SEMINAL VESICLES, URINARY BLADDER, TESTES, EPIDIDYMIDES, FEMUR/KNEE JOINT, STERNUM, NOSE, MANDIBLE Histopathology : LIVER : INFLAMMATION, SUBACUTE/CHRONIC, minimal. No Microscopic Abnormality Observed : KIDNEYS, THYROID GLAND. NOSE, MANDIBLE ^""^^^^^ e H-24516: Subchronic Toxicity 90-Day Gavage Study in Rats with One-Generation Reproduction Evaluations INDIVIDUAL ANIMAL GROSS AND MICROSCOPIC OBSERVATIONS Dose Group : III - 25 nig/kg/day Sex: Males Animal Ref Microscopic & Macroscopic Findings 643180 . Terminal Sacrifice Killed on Day : 91 Exposure Group : 90-DAY EXPOSURE Animal is signed off from necropsy Gross Pathology : No Macroscopic Abnormality Observed : LIVER, KIDNEYS, LUNGS, HEART, SKELETAL MUSCLE, SPLEEN, AORTA, BRAIN, SPINAL CORD, STOMACH, DUODENUM, JEJUNUM, ILEUM, PANCREAS, CECUM, COLON, RECTUM, MESENTERIC LYMPH NODE, SALIVARY GLANDS, MANDIBULAR LYMPH NODE, THYMUS, ADRENAL GLANDS, SCIATIC NERVE, PITUITARY GLAND, THYROID GLAND, PARATHYROID GLANDS, TRACHEA, ESOPHAGUS, - "PHARYNX/LARYNX, EYE(S) WITH OPTIC NERVE, SKIN, PROSTATE, SEMINAL VESICLES, U.RINARY BLADDER, TESTES, EPIDIDYMIDES, FEMUR/KNEE JOINT, STERNUM, NOSE, MANDIBLE Histopathology : LIVER : INFLAMMATION, FATTY CHANGE, FATTY CHANGE, KIDNEYS : SUBACUTE/CHRONIC, minimal. CENTRILOBULAR, minimal. MEDIAN CLEFT, minimal. NEPHROPATHY, CHRONIC PROGRESSIVE, minimal. THYROID GLAND : ALTERATION, COLLOID, minimal. No Microscopic Abnormality Observed : NOSE, MANDIBLE 905 CTOPn)rsan"lled  H-24516: Subchronic Toxicity 90-Day Gavage Study in Rats with One-Generation Reproduction Evaluations INDIVIDUAL ANIMAL GROSS AND MICROSCOPIC OBSERVATIONS Dose Group : III - 25 mg/kg/day Sex: Males Animal Ref Microscopic & Macroscopic Findings 643202 Terminal Sacrifice Killed on Day : 181 Exposure Group : THREE-MONTH RECOVERY Animal is signed off from necropsy Gross Pathology : TESTES : SMALL, SOFT, RIGHT. No Macroscopic Abnormality Observed : LIVER, KIDNEYS, LUNGS, HEART, SKELETAL MUSCLE, SPLEEN, AORTA, BRAIN, SPINAL CORD, STOMACH, DUODENUM, JEJUNUM, ILEUM, PANCREAS, CECUM, COLON, RECTUM, MESENTERIC LYMPH "NODE, SALIVARY GLANDS, MANDIBULAR LYMPH NODE, THYMUS, ADRENAL GLANDS, SCIATIC NERVE, PITUITARY GLAND, THYROID GLAND, PARATHYROID GLANDS. TRACHEA, ESOPHAGUS, PHARYNX/LARYNX, EYE(S) WITH OPTIC NERVE, SKIN, PROSTATE, SEMINAL VESICLES, URINARY BLADDER, EPIDIDYMIDES, FEMUR/KNEE JOINT, STERNUM, NOSE, MANDIBLE Histopathology : THYROID GLAND : ALTERATION, COLLOID, minimal. NOSE : INFLAMMATION, SUBACUTE/CHRONIC, minimal. HYPERPLASIA/HYPERTROPHY, TRANSITIONAL CELL, EPITHELIUM, minimal. HYPERPLASIA/SQUAMOUS METAPLASIA, RESPIRATORY, EPITHELIUM, [B]=BENIGN, minimal. SCHWANNOMA [B]. [M]=MALIGNANT 906 t c  e H-24516: Subchronic Toxicity 90-Day Gavage Study in Rats with One-Generation Reproduction Evaluations INDIVIDUAL ANIMAL GROSS AND MICROSCOPIC OBSERVATIONS Dose Group : III - 25 mg/kg/day Sex: Males Animal Ref Microscopic & Macroscopic Findings 643228 Terminal Sacrifice Killed on Day : 91 Exposure Group : 90-DAY EXPOSURE Animal is signed off from necropsy Gross Pathology : No Macroscopic Abnormality Observed : LIVER, KIDNEYS, LUNGS, HEART, SKELETAL MUSCLE, SPLEEN, AORTA, BRAIN, SPINAL CORD, STOMACH, DUODENUM, JEJUNUM, ILEUM, PANCREAS, CECUM, COLON, RECTUM, MESENTERIC LYMPH NODE, SALIVARY GLANDS, MANDIBULAR LYMPH NODE, THYMUS, ADRENAL GLANDS, SCIATIC NERVE, PITUITARY GLAMD, THYROID GLAND, PARATHYROID GLANDS, TRACHEA, ESOPHAGUS. " PHARYNX/LARYNX, EYE(S) WITH OPTIC NERVE, SKIN, PROSTATE, SEMINAL VESICLES, URINARY BLADDER, TESTES, EPIDIDYMIDES, FEMUR/KMEE JOINT, STERNUM, NOSE, MANDIBLE Histopathology : LIVER : INFLAMMATION, SUBACUTE/CHRONIC, minimal. KIDNEYS : NEPHROPATHY, CHRONIC PROGRESSIVE, minimal. THYROID GLAND : ALTERATION, COLLOID, mild. No Microscopic Abnormality Observed : NOSE, MANDIBLE 907 Company Sanitized. Does not co : n H-24516: Subchronic Toxicity 90-Day Gavage Study in Rats with One-Generation Reproduction Evaluations__ INDIVIDUAL ANIMAL GROSS AND MICROSCOPIC OBSERVATIONS Dose Group : Animal Ref III - 25 mg/kg/day Sex: Males Microscopic & Macroscopic Findings 643240 Terminal Sacrifice Killed on Day : 91 Exposure Group : 90-DAY EXPOSURE Animal is signed off from necropsy Gross Pathology : No Macroscopic Abnormality Observed : LIVER, KIDNEYS, LUNGS, HEART, SKELETAL MUSCLE, SPLEEN, AORTA, BRAIN, SPINAL CORD, STOMACH, DUODENUM, JEJUNUM, ILEUM, PANCREAS, CECUM, COLON, RECTUM, MESENTERIC LYMPH NODE, SALIVARY GLANDS, MANDIBULAR LYMPH NODE, THYMUS, ADRENAL GLANDS, SCIATIC NERVE, PITUITARY GLAND, THYROID GLAND, PARATHYROID GLANDS, TRACHEA, ESOPHAGUS, PHARYNX/LARYNX, EYE(S) WITH OPTIC NERVE, SKIN, PROSTATE, SEMINAL VESICLES, URINARY BLADDER, TESTES, EPIDIDYMIDES, FEMUR/KNEE JOINT, STERNUM, NOSE, MANDIBLE Histopathology : LIVER : INFLAMMATION, SUBACUTE/CHRONIC, THYROID GLAND : ALTERATION, COLLOID, minimal. minimal. No Microscopic Abnormality Observed : KIDNEYS, NOSE, MANDIBLE 908 Company Sanitized. Does not ^ H-24516: Subchronic Toxicity 90-Day Gavage Study in Rats with One-Generation Reproduction Evaluations INDIVIDUAL ANIMAL GROSS AND MICROSCOPIC OBSERVATIONS Dose Group : III - 25 mg/kg/day Sex: Males Animal Ref Microscopic & Macroscopic Findings 643264 Terminal Sacrifice Killed on Day : 91 Exposure Group : 90-DAY EXPOSURE Animal is signed off from necropsy Gross Pathology : No Macroscopic Abnormality Observed : LIVER, KIDNEYS, LUNGS, HEART, SKELETAL MUSCLE, SPLEEN, AORTA, BRAIN, SPINAL CORD, STOMACH, DUODENUM, JEJUNUM, ILEUM, PANCREAS, CECUM, COLON, RECTUM, MESENTERIC LYMPH NODE, SALIVARY GLANDS, MANDIBULAR LYMPH NODE, THYMUS, ADRENAL GLANDS, SCIATIC NERVE, PITUITARY GLAMD, THYROID GLAND, PARATHYROID GLANDS, TRACHEA, ESOPHAGUS, "PHARYNX/LARYNX, EYE(S) WITH OPTIC NERVE, SKIN, PROSTATE, SEMINAL VESICLES, URINARY BLADDER, TESTES, EPIDIDYMIDES, FEMUR/KNEE JOINT, STERNUM, NOSE, MANDIBLE Histopathology : LIVER : INFLAMMATION, SUBACUTE/CHRONIC, minimal. FATTY CHANGE, MEDIAN CLEFT, minimal. THYROID GLAND : ALTERATION, COLLOID, severe. No Microscopic Abnormality Observed : KIDNEYS, NOSE, MANDIBLE 909 Company Sanitized. Does no ^ . . n H-24516: Subchronic Toxicity 90-Day Gavage Study in Rats with One-Generation Reproduction Evaluations INDIVIDUAL ANIMAL GROSS AND MICROSCOPIC OBSERVATIONS Dose Group : III - 25. mg/kg/day Sex: Males Animal Ref Microscopic & Macroscopic Findings 643272 Terminal Sacrifice Killed on Day : 91 Exposure Group : 90-DAY EXPOSURE Animal is signed off from necropsy Gross Pathology : No Macroscopic Abnormality Observed : LIVER, KIDNEYS, LUNGS, HEART, SKELETAL MUSCLE, SPLEEN, AORTA, BRAIN, SPINAL CORD, STOMACH, DUODENUM. JEJUNUM, ILEUM, PANCREAS, CECUM, COLON, RECTUM, MESENTERIC LYMPH NODE, SALIVARY GLANDS, MANDIBULAR LYMPH NODE, THYMUS, ADRENAL GLANDS, SCIATIC NERVE, PITUITARY GLAND, THYROID GLAND, PARATHYROID GLANDS, TRACHEA, ESOPHAGUS, . "PHARYNX/LARYNX, EYE(S) WITH OPTIC NERVE, SKIN, PROSTATE, SEMINAL VESICLES, URINARY BLADDER, TESTES, EPIDIDYMIDES, PEMUR/KNEE JOINT, STERNUM, NOSE, MANDIBLE Histopathology : THYROID GLAND : ALTERATION, COLLOID, mild. No Microscopic Abnormality Observed : LIVER, KIDNEYS, NOSE, MANDIBLE 910 Company Sanitized. Does not H-24516: Subchronic Toxicity 90-Day Gavage Study in Rats with One-Generation Reproduction Evaluations INDIVIDUAL ANIMAL GROSS AND MICROSCOPIC OBSERVATIONS Dose Group : III - 25 mg/kg/day Sex: Males Animal Ref Microscopic & Macroscopic Findings 643290 . Terminal Sacrifice Killed on Day ; 91 Exposure Group : 90-DAY EXPOSURE Animal is signed off from necropsy Gross Pathology : No Macroscopic Abnormality Observed : LIVER, KIDNEYS, LUNGS, HEART, SKELETAL MUSCLE, SPLEEN, AORTA, BRAIN, SPINAL CORD, STOMACH, DUODENUM, JEJUNUM, ILEUM, PANCREAS, CECUM, COLON, RECTUM, MESENTERIC LYMPH NODE, SALIVARY GLANDS, MANDIBULAR LYMPH NODE, THYMUS, ADRENAL GLANDS, SCIATIC NERVE, PITUITARY GLAND, THYROID GLAND, PARATHYROID GLANDS, TRACHEA, ESOPHAGUS, ""PHARYNX/LARYNX, EYE(S) WITH OPTIC NERVE, SKIN, PROSTATE, SEMINAL VESICLES, URINARY BLADDER, TESTES, EPIDIDYMIDES, FEMUR/KNEE JOINT, STERNUM, NOSE, MANDIBLE Histopathology : LIVER : INFLAMMATION, SUBACUTE/CHRONIC, minimal. FATTY CHANGE, CENTRILOBULAR, minimal. THYROID GLAND : . ALTERATION, COLLOID, minimal. No Microscopic Abnormality Observed : KIDNEYS, NOSE, MANDIBLE 911 Company Sanitized. Does no! contain H-24516: Subchronic Toxicity 90-Day Gavage Study in Rats with One-Generation Reproduction Evaluations INDIVIDUAL ANIMAL GROSS AND MICROSCOPIC OBSERVATIONS Dose Group : III - 25 mg/kg/day Sex: Males Animal Ref Microscopic & Macroscopic Findings 643292 . Terminal Sacrifice Killed on Day : 91 Exposure Group : 90-DAY EXPOSURE Animal is signed off from necropsy Gross Pathology : No Macroscopic Abnormality Observed : LIVER, KIDNEYS, LUNGS, HEART, SKELETAL MUSCLE, SPLEEN, AORTA, BRAIN, SPINAL CORD, STOMACH, DUODENUM, JEJUNUM, ILEUM, PANCREAS, CECUM, COLON. RECTUM, MESENTERIC LYMPH NODE, SALIVARY GLANDS, MANDIBULAR LYMPH NODE, THYMUS, ADRENAL GLANDS, SCIATIC NERVE, PITUITARY GLAND, THYROID GLAND, PARATHYROID GLANDS, TRACHEA, ESOPHAGUS, . "PHARYNX/LARYNX, EYE(S) WITH OPTIC NERVE, SKIN, PROSTATE, SEMINAL VESICLES, URINARY BLADDER, TESTES, EPIDIDYMIDES, FEMUR/KNEE JOINT, STERNUM, NOSE, MANDIBLE Histopathology : LIVER : INFLAMMATION, SUBACUTE/CHRONIC, minimal. KIDNEYS : NEPHROPATHY, CHRONIC PROGRESSIVE, minimal. THYROID GLAND : ALTERATION, COLLOID, minimal. No Microscopic Abnormality Observed : NOSE, MANDIBLE 912 Company Sanitized. Does no H-24516: Subchronic Toxicity 90-Day Gavage Study in Rats with One-Generation Reproduction Evaluations INDIVIDUAL ANIMAL GROSS AMD MICROSCOPIC OBSERVATIONS Dose Group : III - 25 mg/kg/day Sex: Males Animal Ref Microscopic & Macroscopic Findings 643293 . Terminal Sacrifice Killed on Day : 181 Exposure Group : THREE-MONTH RECOVERY Animal is signed off from necropsy Gross Pathology : No Macroscopic Abnormality Observed : LIVER, KIDNEYS, LUNGS, HEART, SKELETAL MUSCLE, SPLEEN, AORTA, BRAIN, SPINAL CORD, STOMACH, DUODENUM, JEJUNUM, ILEUM, PANCREAS, CECUM, COLON, RECTUM, MESENTERIC LYMPH NODE, SALIVARY GLANDS, MANDIBULAR LYMPH NODE, THYMUS, ADRENAL GLANDS, SCIATIC NERVE, PITUITARY GLAND, THYROID GLAND, PARATHYROID GLANDS, TRACHEA, ESOPHAGUS, . 'PHARYNX/LARYNX, EYE(S) WITH OPTIC NERVE, SKIN, PROSTATE, SEMINAL VESICLES, URINARY BLADDER, TESTES, EPIDIDYMIDES, FEMUR/KNEE JOINT, STERNUM, NOSE, MANDIBLE Histopathology : THYROID GLAND : ALTERATION, COLLOID, mild. NOSE : INFLAMMATION, SUBACUTE/CHRONIC, minimal. HYPERPLASIA/HYPERTROPHY,TRANSITIONAL CELL, minimal. EPITHELIUM, 913 Company Sanitized. Does not H-24516: Subchronic Toxicity 90-Day Gavage Study in Rats with One-Generation Reproduction Evaluations INDIVIDUAL ANIMAL GROSS AND MICROSCOPIC OBSERVATIONS Dose Group : III - 25.mg/kg/day Sex: Males Animal Ref Microscopic & Macroscopic Findings 643305 Terminal Sacrifice Killed on Day : 181 Exposure Group : THREE-MONTH RECOVERY Animal is signed off from necropsy Gross Pathology : No Macroscopic Abnormality Observed : LIVER, KIDNEYS, LUNGS, HEART, SKELETAL MUSCLE, SPLEEN, AORTA, BRAIN, SPINAL CORD, STOMACH, DUODENUM. JEJUNUM. ILEUM, PANCREAS, CECUM, COLON, RECTUM, MESENTERIC LYMPH NODE, SALIVARY GLANDS, MANDIBULAR LYMPH NODE, THYMUS, . ADRENAL GLANDS, SCIATIC NERVE, PITUITARY GLAND, THYROID GLAND, PARATHYROID GLANDS, TRACHEA, ESOPHAGUS, -PHARYNX/LARYNX, EYE(S) WITH OPTIC NERVE, SKIN, PROSTATE, SEMINAL VESICLES, URINARY BLADDER, TESTES, EPIDIDYMIDES, FEMUR/KNEE JOINT, STERNUM, NOSE, MANDIBLE Histopathology : THYROID GLAND : ALTERATION, COLLOID, severe. NOSE : INFLAMMATION, SUBACUTE/CHRONIC, NASOLACRIMAL DUCT, mild. 914 tompany Sanitized. Does not H-24516: Subchronic Toxicity 90-Day Gavage Study in Rats with One-Generation Reproduction Evaluations INDIVIDUAL ANIMAL GROSS AND MICROSCOPIC OBSERVATIONS Dose Group : III - 25 mg/kg/day Sex: Males Animal Ref Microscopic & Macroscopic Findings 643306 Terminal Sacrifice Killed on Day : 181 Exposure Group : THREE-MONTH RECOVERY Animal is signed off from necropsy Gross Pathology : No Macroscopic Abnormality Observed : LIVER, KIDNEYS, LUNGS, HEART, SKELETAL MUSCLE, SPLEEN, AORTA, BRAIN, SPINAL CORD, STOMACH, DUODENUM, JEJUNUM, ILEUM, PANCREAS. CECUM, COLON, RECTUM, MESENTERIC LYMPH NODE, SALIVARY GLANDS, MANDIBULAR LYMPH NODE, THYMUS, ADRENAL GLANDS, SCIATIC NERVE, PITUITARY GLAND, THYROID GLAND, PARATHYROID GLANDS, TRACHEA, ESOPHAGUS, - -PHARYNX/LARYNX, EYE(S) WITH OPTIC NERVE, SKIN, PROSTATE, SEMINAL VESICLES, URINARY BLADDER, TESTES, EPIDIDYMIDES, FEMUR/KNEE JOINT, STERNUM, NOSE, MANDIBLE Histopathology : .. THYROID GLAND : ALTERATION, COLLOID, mild. No Microscopic Abnormality Observed : NOSE 915 Company SanMzed. Does H-24516: Subchronic Toxicity 90-Day Gavage Study in Rats with One-Generation Reproduction Evaluations INDIVIDUAL ANIMAL GROSS AND MICROSCOPIC OBSERVATIONS Dose Group : Animal Ref III - 25 mg/kg/day Sex: Males Microscopic & Macroscopic Findings 643308 . Terminal Sacrifice Killed on Day : 91 Exposure Group : 90-DAY EXPOSURE Animal is signed off from necropsy Gross Pathology : No Macroscopic Abnormality Observed : LIVER, KIDNEYS, LUNGS, HEART, SKELETAL MUSCLE, SPLEEN, AORTA, BRAIN, SPINAL CORD, STOMACH, DUODENUM, JEJUNUM, ILEUM, PANCREAS, CECUM, COLON, RECTUM, MESENTERIC LYMPH NODE, SALIVARY GLANDS, MANDIBULAR LYMPH NODE, THYMUS, ADRENAL GLANDS, SCIATIC NERVE, PITUITARY GLAND, THYROID GLAND, PARATHYROID GLANDS, TRACHEA, ESOPHAGUS. .'PHARYNX/LARYNX, EYE(S) WITH OPTIC NERVE, SKIN, PROSTATE, SEMINAL VESICLES, URINARY BLADDER, TESTES, EPIDIDYMIDES, FEMUR/KNEE JOINT, STERNUM, NOSE, MANDIBLE Histopathology : LIVER : INFLAMMATION, SUBACUTE/CHRONIC, THYROID GLAND : ALTERATION, COLLOID, minimal. minimal. No Microscopic Abnormality Observed : KIDNEYS, NOSE, MANDIBLE 916 Company SanBlzed. Doe. not co  H-24516: Subchronic Toxicity 90-Day Gavage Study in Rats with One-Generation Reproduction Evaluations INDIVIDUAL ANIMAL GROSS AND MICROSCOPIC OBSERVATIONS Dose Group : III - 25 mg/kg/day Sex: Males Animal Ref Microscopic & Macroscopic Findings 643310 . Terminal Sacrifice Killed on Day : 181 Exposure Group : THREE-MONTH RECOVERY Animal is signed off from necropsy Gross Pathology : No Macroscopic Abnormality Observed : LIVER, KIDNEYS, LUNGS, HEART, SKELETAL MUSCLE, SPLEEN, AORTA, BRAIN, SPINAL CORD, STOMACH, DUODENUM, JEJUNUM. ILEUM, PANCREAS, CECUM, COLON, RECTUM, MESENTERIC LYMPH NODE, SALIVARY GLANDS, MANDIBULAR LYMPH NODE, THYMUS, ADRENAL GLANDS, SCIATIC NERVE, PITUITARY GLAND, THYROID GLAMD, PARATHYROID GLANDS, TRACHEA, ESOPHAGUS, 'PHARYNX/LARYNX, EYE(S) WITH OPTIC NERVE, SKIN, PROSTATE, SEMINAL VESICLES, URINARY BLADDER, TESTES, EPIDIDYMIDES, FEMUR/KNEE JOINT, STERNUM, NOSE, MANDIBLE Histopathology : THYROID GLAND : ALTERATION, COLLOID, severe. NOSE : INFLAMMATION, SUBACUTE/CHRONIC, mild. HYPERPLASIA/HYPERTROPHY, TRANSITIONAL mild. CELL, EPITHELIUM, 917 Company Sanitized. Does not c dS&, H-24516: Subchronic Toxicity 90-Day Gavage Study in Rats with One-Generation Reproduction Evaluations INDIVIDUAL ANIMAL GROSS AND MICROSCOPIC OBSERVATIONS Dose Group : V - 100 nig/kg/day Sex; Males Animal Ref Microscopic & Macroscopic Findings 643159 Terminal Sacrifice Killed on Day : 181 Exposure Group : THREE-MONTH RECOVERY Animal is signed off from necropsy Gross Pathology : No Macroscopic Abnormality Observed : LIVER, KIDNEYS, LUNGS, HEART, SKELETAL MUSCLE, SPLEEN, AORTA, BRAIN, SPINAL CORD, STOMACH, DUODENUM, JEJUNUM, ILEUM, PANCREAS, CECUM, COLON, RECTUM, MESENTERIC LYMPH NODE, SALIVARY GLANDS, MANDIBULAR LYMPH NODE, THYMUS, ADRENAL GLANDS, SCIATIC NERVE, PITUITARY GLAND, THYROID GLAND, PARATHYROID GLANDS, TRACHEA, ESOPHAGUS, "PHARYNX/LARYNX, EYE(S) WITH OPTIC NERVE, SKIN, PROSTATE, SEMINAL VESICLES, URINARY BLADDER, TESTES, EPIDIDYMIDES, FEMUR/KNEE JOINT, STERNUM, NOSE, MANDIBLE Histopathology : LIVER : INFLAMMATION, SUBACUTE/CHRONIC, minimal. THYROID GLAMD : ALTERATION, COLLOID, severe. NOSE : INFLAMMATION, SUBACUTE/CHRONIC, mild. DEGENERATION, AMELOBLASTS, minimal. HYPERPLASIA/SQUAMOUS METAPLASIA, RESPIRATORY, minimal. FRACTURE/CALLUS, TOOTH. EPITHELIUM, 918 Company Sanitized. Does ^ H-24516: Subchronic Toxicity 90-Day Gavage Study in Rats with One-Generation Reproduction Evaluations INDIVIDUAL ANIMAL GROSS AND MICROSCOPIC OBSERVATIONS Dose Group : V - 100 mg/kg/day Sex: Males Animal Ref 643169 . Microscopic & Macroscopic Findings Terminal Sacrifice Killed on Day : 181 Exposure Group : THREE-MONTH RECOVERY Animal is signed off from necropsy Gross Pathology : No Macroscopic Abnormality Observed : LIVER, KIDNEYS, LUNGS, HEART, SKELETAL MUSCLE, SPLEEN, AORTA, BRAIN, SPINAL CORD, STOMACH, DUODENUM, JEJUNUM, ILEUM, PANCREAS. CECUM, COLON, RECTUM, MESENTERIC LYMPH NODE, SALIVARY GLANDS, MAMDIBULAR LYMPH NODE, THYMUS, ADRENAL GLANDS, SCIATIC NERVE, PITUITARY GLAND, THYROID GLAND, PARATHYROID GLANDS, TRACHEA, ESOPHAGUS, "PHARYNX/LARYNX, EYE(S) WITH OPTIC NERVE, SKIN, PROSTATE, SEMINAL VESICLES, .URINARY BLADDER, TESTES, EPIDIDYMIDES, FEMUR/KNEE JOINT, STERNUM, NOSE, MANDIBLE Histopathology : LIVER : INFLAMMATION, SUBACUTE/CHRONIC, NECROSIS, FOCAL, minimal. THYROID GLAND : ALTERATION, COLLOID, severe. minimal. No Microscopic Abnormality Observed : NOSE 919 Company Sanitized. Does not 6 . H-24516: Subchronic Toxicity 90-Day Gavage Study in Rats with One-Generation Reproduction Evaluations INDIVIDUAL ANIMAL GROSS AND MICROSCOPIC OBSERVATIONS Dose Group : V - 100 mg/kg/day Sex: Males Animal Ref Microscopic & Macroscopic Findings 643175 . Accidentally Killed Duration of dosing-days: 77 Exposure Group : 90-DAY EXPOSURE Animal is signed off from necropsy Gross Pathology : LIVER : DISCOLORATION, TAN, LEFT. No Macroscopic Abnormality Observed : KIDNEYS, LUNGS, HEART, SKELETAL MUSCLE, SPLEEN, AORTA, BRAIN, SPINAL CORD, STOMACH, DUODENUM, JEJUNUM, ILEUM, PANCREAS, CECUM, COLON, RECTUM, MESENTERIC LYMPH NODE, "SALIVARY GLANDS, MANDIBULAR LYMPH NODE, THYMUS, ADRENAL GLANDS, SCIATIC NERVE, PITUITARY GLAND, THYROID GLAND, PARATHYROID GLANDS, TRACHEA, ESOPHAGUS, PHARYNX/LARYNX, EYE(S) WITH OPTIC NERVE, SKIN, PROSTATE, SEMINAL VESICLES, URINARY BLADDER, TESTES, EPIDIDYMIDES, FEMUR/KNEE JOINT, STERNUM, NOSE Histopathology : 643175 LIVER : HYPERTROPHY, KIDNEYS : HEPATOCYTE, CENTRILOBULAR, minimal. NEPHROPATHY, CHRONIC PROGRESSIVE, minimal. LUNGS : INFLAMMATION, GRANULOMATOUS, severe. HEART : INFLAMMATION, SUBACUTE/CHRONIC, moderate. THYMUS : NOT PRESENT. Continued on the next page .... 920 Company Sanitized. Does not conta ^ ^ H-24516: Subchronic Toxicity 90-Day Gavage Study in Rats with One-Generation Reproduction Evaluations INDIVIDUAL ANIMAL GROSS AND MICROSCOPIC OBSERVATIONS Dose Group : V - 100 mg/kg/day Sex: Males Animal Ref Microscopic & Macroscopic Findings 643175 . Continued from previous page Histopathology : PARATHYROID GLANDS : NOT PRESENT. ESOPHAGUS : INFLAMMATION, SUBACUTE/CHRONIC, moderate. PROSTATE : INFLAMMATION, SUBACUTE/CHRONIC, minimal. TESTES : SPERMATID RETENTION, SEMINIFEROUS TUBULES, BONE MARROW : minimal. HYPERPLASIA, GRANULOCYTIC, moderate. NOSE" : DEGENERATION/NECROSIS, RESPIRATORY, EPITHELIUM, INFLAMMATION, SUBACUTE/CHRONIC, mild. NON-PROTOCOL TISSUE : Moderate, ABSCESS, SUBCUTIS. minimal. No Microscopic Abnormality Observed : SKELETAL MUSCLE, SPLEEN, AORTA, BRAIN, SPINAL CORD, STOMACH, DUODENUM, JEJUNUM, ILEUM, PANCREAS, CECUM, COLON, RECTUM, MESENTERIC LYMPH NODE, SALIVARY GLANDS, MANDIBULAR LYMPH NODE, ADRENAL GLANDS, PITUITARY GLAND, THYROID GLAND, TRACHEA, PHARYNX/LARYNX, EYE(S) WITH OPTIC NERVE, SKIN, SEMINAL VESICLES, URINARY BLADDER, EPIDIDYMIDES, FEMUR/KNEE JOINT, STERNUM 921 Cowwnv Sant'ted. Does not co H-24516: Subchronic Toxicity 90-Day Gavage Study in Rats with One-Generation Reproduction Evaluations INDIVIDUAL ANIMAL GROSS AND MICROSCOPIC OBSERVATIONS Dose Group : v - 100 mg/kg/day Sex: Males Animal Ref Microscopic & Macroscopic Findings 643181 Terminal Sacrifice Killed on Day : 181 Exposure Group : THREE-MONTH RECOVERY Animal is signed off from necropsy Gross Pathology : No Macroscopic Abnormality Observed : LIVER, KIDNEYS, LUNGS, HEART, SKELETAL MUSCLE, SPLEEN, AORTA, BRAIN, SPINAL CORD, STOMACH, DUODENUM, JEJUNUM, ILEUM, PANCREAS, CECUM, COLON, RECTUM, MESENTERIC LYMPH NODE, SALIVARY GLANDS, MANDIBULAR LYMPH NODE, THYMUS, ADRENAL GLANDS, SCIATIC NERVE, PITUITARY GLAND, THYROID GLAND, PARATHYROID GLANDS, TRACHEA, ESOPHAGUS, ""PHARYNX/LARYNX, EYE(S) WITH OPTIC NERVE, SKIN, PROSTATE, SEMINAL VESICLES, URINARY BLADDER, TESTES, EPIDIDYMIDES, FEMUR/KMEE JOINT, STERNUM, NOSE, MANDIBLE Histopathology : LIVER : S INFLAMMATION, SUBACUTE/CHRONIC, minimal. THYROID GLAND : ALTERATION, COLLOID, severe. NOSE : INFLAMMATION, SUBACUTE/CHRONIC, mild. HYPERPLASIA/SQUAMOUS METAPLASIA, RESPIRATORY, EPITHELIUM, mild. INFLAMMATION, SUBACUTE/CHRONIC, NASOLACRIMAL DUCT, mild. 922 Company Sanitized. Does n H-24516: Subchronic Toxicity 90-Day Gavage Study in Rats with One-Generation Reproduction Evaluations INDIVIDUAL ANIMAL GROSS AND MICROSCOPIC OBSERVATIONS Dose Group : V - 100 mg/kg/day Sex: Males Animal Ref Microscopic & Macroscopic Findings 643206 Terminal Sacrifice Killed on Day : 181 Exposure Group : THREE-MONTH RECOVERY Animal is signed off from necropsy Gross Pathology : No Macroscopic Abnormality Observed : LIVER, KIDNEYS, LUNGS, 'HEART, SKELETAL MUSCLE, SPLEEN, AORTA, BRAIN, SPINAL CORD, STOMACH, DUODENUM, JEJUNUM, ILEUM, PANCREAS, CECUM, COLON, RECTUM, MESENTERIC LYMPH NODE, SALIVARY GLANDS, MANDIBULAR LYMPH NODE, THYMUS, ADRENAL GLANDS, SCIATIC NERVE, PITUITARY GLAND, THYROID GLAND, PARATHYROID GLANDS, TRACHEA, ESOPHAGUS, " "PHARYNX/LARYNX, EYE(S) WITH OPTIC NERVE, SKIN, PROSTATE, SEMINAL VESICLES, URINARY BLADDER, TESTES, EPIDIDYMIDES, FEMUR/KNEE JOINT, STERNUM, NOSE, MANDIBLE Histopathology : LIVER : INFLAMMATION, SUBACUTE/CHRONIC, NECROSIS, FOCAL, minimal. THYROID GLAND : ALTERATION, COLLOID, severe. minimal. No Microscopic Abnormality Observed : NOSE 923 ^ ^ H-24516: Subchronic Toxicity 90-Day Gavage Study in Rats with One-Generation Reproduction Evaluations INDIVIDUAL ANIMAL GROSS AND MICROSCOPIC OBSERVATIONS Dose Group : V - 100 mg/kg/day Sex: Males Animal Ref Microscopic & Macroscopic Findings 643224 Terminal Sacrifice Killed on Day : 91 Exposure Group : 90-DAY EXPOSURE Animal is signed off from necropsy Gross Pathology : No Macroscopic Abnormality Observed : LIVER, KIDNEYS, LUNGS, HEART, SKELETAL MUSCLE, SPLEEN, AORTA, BRAIN, SPINAL CORD, STOMACH, DUODENUM, JEJUNUM, ILEUM, PANCREAS, CECUM, COLON, RECTUM, MESENTERIC LYMPH NODE, SALIVARY GLANDS, MANDIBULAR LYMPH NODE, THYMUS, ADRENAL GLANDS, SCIATIC NERVE, PITUITARY GLAND. THYROID GLAND, PARATHYROID GLANDS, TRACHEA, ESOPHAGUS, .'PHARYNX/LARYNX, EYE(S) WITH OPTIC NERVE, SKIN, PROSTATE, SEMINAL VESICLES, URINARY BLADDER, TESTES, EPIDIDYMIDES, FEMUR/KNEE JOINT, STERNUM, NOSE, MANDIBLE Histopathology : LIVER : INFLAMMATION, SUBACUTE/CHRONIC, minimal. HYPERTROPHY, HEPATOCYTE, CENTRILOBULAR. minimal. FATTY CHANGE, CENTRILOBULAR, minimal. THYROID GLAND : ALTERATION, COLLOID, severe. HYPERTROPHY, FOLLICULAR, minimal. No Microscopic Abnormality Observed : KIDNEYS, NOSE, MANDIBLE 924 -< "^^^'^^^r H-24516: Subchronic Toxicity 90-Day Gavage Study in Rats with One-Generation Reproduction Evaluations INDIVIDUAL ANIMAL GROSS AND MICROSCOPIC OBSERVATIONS Dose Group : V - 100 mg/kg/day Sex: Males Animal Ref Microscopic & Macroscopic Findings 643243 Terminal Sacrifice Killed on Day : 91 Exposure Group : 90-DAY EXPOSURE Animal is signed off from necropsy Gross Pathology : No Macroscopic Abnormality Observed : LIVER, KIDNEYS, LUNGS, HEART, SKELETAL MUSCLE, SPLEEN, AORTA, BRAIN, SPINAL CORD, STOMACH, DUODENUM, JEJUNUM, ILEUM, PANCREAS, CECUM, COLON, RECTUM, MESENTERIC LYMPH NODE, SALIVARY GLANDS, MANDIBULAR LYMPH MODE, THYMUS, ADRENAL GLANDS, SCIATIC NERVE, PITUITARY GLAND, THYROID GLAND, PARATHYROID GLANDS, TRACHEA, ESOPHAGUS, "'PHARYNX/LARYNX, EYE(S) WITH OPTIC NERVE, SKIN, PROSTATE, SEMINAL VESICLES, URINARY BLADDER, TESTES, EPIDIDYMIDES, FEMUR/KNEE JOINT, STERNUM, NOSE, MANDIBLE Histopathology : LIVER : INFLAMMATION, SUBACUTE/CHRONIC, minimal. HYPERTROPHY, HEPATOCYTE, CENTRILOBULAR, minimal. FATTY CHANGE, CENTRILOBULAR, minimal. THYROID GLAND : ALTERATION, COLLOID, minimal. No Microscopic Abnormality Observed : KIDNEYS, NOSE, MANDIBLE 925 CompanySanitized. Does not c H-24516: Subchronic Toxicity 90-Day Gavage Study in Rats with One-Generation Reproduction Evaluations INDIVIDUAL ANIMAL GROSS AND MICROSCOPIC OBSERVATIONS Dose Group : V - 100 ing/kg/day Sex: Males Animal Ref Microscopic & Macroscopic Findings 643247 . Terminal Sacrifice Killed on Day : 91 Exposure Group : 90-DAY EXPOSURE Animal is signed off from necropsy Gross Pathology : No Macroscopic Abnormality Observed : LIVER, KIDNEYS, LUNGS, HEART, SKELETAL MUSCLE, SPLEEN, AORTA, BRAIN, SPINAL CORD, STOMACH, DUODENUM, JEJUNUM, ILEUM, PANCREAS, CECUM, COLON, RECTUM, MESENTERIC LYMPH NODE, SALIVARY GLANDS, MANDIBULAR LYMPH NODE, THYMUS, ADRENAL GLANDS, SCIATIC NERVE, PITUITARY GLAND,- THYROID GLAND, PARATHYROID GLANDS, TRACHEA, ESOPHAGUS, ""PHARYNX/LARYNX, EYE(S) WITH OPTIC NERVE, SKIN, PROSTATE, SEMINAL VESICLES, URINARY BLADDER, TESTES, EPIDIDYMIDES, FEMUR/KNEE JOINT, STERNUM, NOSE, MANDIBLE Histopathology : LIVER : INFLAMMATION, SUBACUTE/CHRONIC, minimal. HYPERTROPHY, HEPATOCYTE, CENTRILOBULAR, minimal. . KIDNEYS : NEPHROPATHY, CHRONIC PROGRESSIVE, minimal. THYROID GLAND : ALTERATION, COLLOID, severe. NOSE : DEGENERATION, AMELOBLASTS, minimal. No Microscopic Abnormality Observed : MANDIBLE 926 Company Sanitized. Does not cont ^ ^ H-24516: Subchronic Toxicity 90-Day Gavage Study in Rats with One-Generation Reproduction Evaluations INDIVIDUAL ANIMAL GROSS AND MICROSCOPIC OBSERVATIONS Dose Group : V - 100 mg/kg/day Sex: Males Animal Ref 643250 . Microscopic & Macroscopic Findings Terminal Sacrifice Killed on Day : 91 Exposure Group : 90-DAY EXPOSURE Animal is signed off from necropsy Gross Pathology : No Macroscopic Abnormality Observed : LIVER, KIDNEYS, LUNGS, HEART, SKELETAL MUSCLE, SPLEEN, AORTA, BRAIN, SPINAL CORD, STOMACH, DUODENUM, JEJUNUM, ILEUM, PANCREAS, CECUM, COLON, RECTUM, MESENTERIC LYMPH NODE, SALIVARY GLANDS, MANDIBULAR LYMPH NODE, THYMUS, ADRENAL GLANDS, SCIATIC NERVE, PITUITARY GLAND, THYROID GLAND, PARATHYROID GLANDS, TRACHEA, ESOPHAGUS, "PHARYNX/LARYNX, EYE(S) WITH OPTIC NERVE, SKIN, PROSTATE, SEMINAL VESICLES, URINARY BLADDER, TESTES, EPIDIDYMIDES, FEMUR/KNEE JOINT, STERNUM, NOSE, MANDIBLE Histopathology : LIVER : INFLAMMATION, SUBACUTE/CHRONIC, minimal. FATTY CHANGE, MEDIAN CLEFT, mild. THYROID GLAND : ALTERATION, COLLOID, severe. No Microscopic Abnormality Observed : KIDNEYS, NOSE, MANDIBLE 927 Company Sanitized. Does not cont ^ H-24516: Subchronic Toxicity 90-Day Gavage Study in Rats with One-Generation Reproduction Evaluations INDIVIDUAL ANIMAL GROSS AND MICROSCOPIC OBSERVATIONS Dose Group ; V - 100 mg/kg/day Sex: Males Animal Ref Microscopic & Macroscopic Findings 643257 . Terminal Sacrifice Killed on Day : 91 Exposure Group : 90-DAY EXPOSURE Animal is signed off from necropsy Gross Pathology : No Macroscopic Abnormality Observed : LIVER, KIDNEYS, LUNGS, HEART, SKELETAL MUSCLE, SPLEEN, AORTA, BRAIN, SPINAL CORD, STOMACH, DUODENUM, JEJUNUM, ILEUM, PANCREAS, CECUM, COLON, RECTUM, MESENTERIC LYMPH NODE, SALIVARY GLANDS, MANDIBULAR LYMPH NODE, THYMUS, ADRENAL GLANDS, SCIATIC NERVE, PITUITARY GLAND, THYROID GLAND, PARATHYROID GLANDS, TRACHEA, ESOPHAGUS, -"PHARYNX/LARYNX, EYE(S) WITH OPTIC NERVE, SKIN, PROSTATE, SEMINAL VESICLES, URINARY BLADDER, TESTES, EPIDIDYMIDES, FEMUR/KNEE JOINT, STERNUM, NOSE, MANDIBLE Histopathology : LIVER : INFLAMMATION, SUBACUTE/CHRONIC, minimal. HYPERTROPHY, HEPATOCYTE, CENTRILOBULAR, FATTY CHANGE, FATTY CHANGE, THYROID GLAND : CENTRILOBULAR, minimal. MEDIAN CLEFT, minimal. ALTERATION, COLLOID, minimal. NOSE : DEGENERATION, AMELOBLASTS, minimal. minimal. No Microscopic Abnormality Observed : KIDNEYS, MANDIBLE 928 Company Sanitized. Does not conta  _ H-24516: Subchronic Toxicity 90-Day Gavage Study in Rats with One-Generation Reproduction Evaluations INDIVIDUAL ANIMAL GROSS AND MICROSCOPIC OBSERVATIONS Dose Group : V - 100 mg/kg/day Sex: Males Animal Ref Microscopic & Macroscopic Findings 643275 Terminal Sacrifice Killed on Day : 91 Exposure Group : 90-DAY EXPOSURE Animal is signed off from necropsy Gross Pathology : No Macroscopic Abnormality Observed : LIVER, KIDNEYS, LUNGS, HEART, SKELETAL MUSCLE, SPLEEN, AORTA, BRAIN, SPINAL CORD, STOMACH, DUODENUM, JEJUNUM, ILEUM, PANCREAS, CECUM, COLON, RECTUM, MESENTERIC LYMPH NODE, SALIVARY GLANDS, MANDIBULAR LYMPH NODE, THYMUS, ADRENAL GLANDS, SCIATIC NERVE, PITUITARY GLAND, THYROID GLAND, PARATHYROID GLANDS, TRACHEA, ESOPHAGUS, - "PHARYNX/LARYNX, EYE(S) WITH OPTIC NERVE, SKIN, PROSTATE, SEMINAL VESICLES, URINARY BLADDER, TESTES, EPIDIDYMIDES, FEMUR/KNEE JOINT. STERNUM, NOSE, MANDIBLE Histopathology : LIVER : INFLAMMATION, SUBACUTE/CHRONIC, minimal. HYPERTROPHY, HEPATOCYTE, CENTRILOBULAR, FATTY CHANGE, CENTRILOBULAR, minimal. KIDNEYS : HYPERTROPHY, TUBULAR, minimal. THYROID GLAND : ALTERATION, COLLOID, severe. NOSE : DEGENERATION, AMELOBLASTS, minimal. MANDIBLE : DEGENERATION, AMELOBLASTS, minimal. minimal. 929 Company Sanitized. Does not con ' ^; .. ^; H-24516: Subchronic Toxicity 90-Day Gavage Study in Rats with One-Generation Reproduction Evaluations INDIVIDUAL ANIMAL GROSS AND MICROSCOPIC OBSERVATIONS Dose Group : V - 100 mg/kg/day Sex: Males Animal Ref Microscopic & Macroscopic Findings 643286 . Terminal Sacrifice Killed on Day : 181 Exposure Group : THREE-MONTH RECOVERY Animal is signed off from necropsy Gross Pathology : No Macroscopic Abnormality Observed : LIVER, KIDNEYS, LUNGS, HEART, SKELETAL MUSCLE, SPLEEN, AORTA, BRAIN, SPINAL CORD, STOMACH, DUODENUM, JEJUNUM, ILEUM, PANCREAS, CECUM, COLON, RECTUM, MESENTERIC LYMPH NODE, SALIVARY GLANDS, MANDIBULAR LYMPH NODE, THYMUS, ADRENAL GLANDS, SCIATIC NERVE, PITUITARY GLAND, THYROID GLAND, PARATHYROID GLANDS, TRACHEA, ESOPHAGUS, .'PHARYNX/LARYNX, EYE(S) WITH OPTIC NERVE, SKIN, PROSTATE, SEMINAL VESICLES, URINARY BLADDER, TESTES, EPIDIDYMIDES, FEMUR/KNEE JOINT, STERNUM, NOSE, MANDIBLE Histopathology : LIVER : INFLAMMATION, SUBACUTE/CHRONIC, THYROID GLAND : ALTERATION, COLLOID, severe. minimal. No Microscopic Abnormality Observed : NOSE 930 Company Sanitized. Does not conta -24516: Subchronic Toxicity 90-Day Gavage Study in Rats with One-Generation Reproduction Evaluations INDIVIDUAL ANIMAL GROSS AND MICROSCOPIC OBSERVATIONS Dose Group : V - 100 ing/kg/day Sex: Males Animal Ref Microscopic & Macroscopic Findings 643311 Terminal Sacrifice Killed on Day : 91 Exposure Group : 90-DAY EXPOSURE Animal is signed off from necropsy Gross Pathology : No Macroscopic Abnormality Observed : LIVER, KIDNEYS, LUNGS, HEART, SKELETAL MUSCLE, SPLEEN, AORTA, BRAIN, SPINAL CORD, STOMACH, DUODENUM, JEJUNUM, ILEUM, PANCREAS, CECUM, COLON, RECTUM, MESENTERIC LYMPH NODE, SALIVARY GLANDS, MANDIBULAR LYMPH NODE, THYMUS, ADRENAL GLANDS, SCIATIC NERVE. PITUITARY GLAND, THYROID GLAND, PARATHYROID GLANDS, TRACHEA, ESOPHAGUS, - "PHARYNX/LARYNX, EYE(S) WITH OPTIC NERVE, SKIN, PROSTATE, SEMINAL VESICLES, URINARY BLADDER, TESTES, EPIDIDYMIDES, FEMUR/KNEE JOINT, STERNUM, NOSE, MANDIBLE Histopathology ; LIVER : INFLAMMATION, SUBACUTE/CHRONIC, minimal. HYPERTROPHY, HEPATOCYTE, CENTRILOBULAR, minimal. FATTY CHANGE, CENTRILOBULAR, minimal. NECROSIS, FOCAL, minimal. KIDNEYS : NEPHROPATHY, CHRONIC PROGRESSIVE, minimal. THYROID GLAND : ALTERATION, COLLOID, mild. NOSE ; DEGENERATION, AMELOBLASTS, minimal. 643311 Continued on the next page .... 931 Company Sanitized. Does not cont H-24516: Subchronic Toxicity 90-Day Gavage Study in Rats with One-Generation Reproduction Evaluations INDIVIDUAL ANIMAL GROSS AND MICROSCOPIC OBSERVATIONS Dose Group : V - 100 mg/kg/day Sex: Males Animal Ref 643311 Microscopic & Macroscopic Findings Continued from previous page Histopathology : No Microscopic Abnormality Observed : MANDIBLE 643314 Terminal Sacrifice Killed on Day : 91 Exposure Group : 90-DAY EXPOSURE Animal is signed off from necropsy Gross Pathology : No- Macroscopic Abnormality Observed : LIVER, KIDNEYS, LUNGS, HEART, SKELETAL MUSCLE, SPLEEN, AORTA, BRAIN, SPINAL CORD, STOMACH, DUODENUM, JEJUNUM, ILEUM, PANCREAS, CECUM, COLON, RECTUM, MESENTERIC LYMPH NODE, SALIVARY GLANDS, MANDIBULAR LYMPH NODE, THYMUS, ADRENAL GLANDS, SCIATIC NERVE, PITUITARY GLAND, THYROID GLAND, PARATHYROID GLANDS, TRACHEA, ESOPHAGUS, PHARYNX/LARYNX, EYE(S) WITH OPTIC NERVE, SKIN, PROSTATE, SEMINAL VESICLES, URINARY BLADDER. TESTES, EPIDIDYMIDES, FEMUR/KNEE JOINT, STERNUM, NOSE, MANDIBLE Histopathology : 643314 LIVER : INFLAMMATION, SUBACUTE/CHRONIC, minimal. HYPERTROPHY, HEPATOCYTE, CENTRILOBULAR, minimal. KIDNEYS : NEPHROPATHY, CHRONIC PROGRESSIVE, minimal. Continued on the next page .... 932 Company Sanitized. Does no H-24516: Subchronic Toxicity 90-Day Gavage Study in Rats with One-Generation Reproduction Evaluations INDIVIDUAL ANIMAL GROSS AND MICROSCOPIC OBSERVATIONS Dose Group : V - 100 mg/kg/day Sex: Males Animal Ref Microscopic & Macroscopic Findings 643314 Continued from previous page Histopathology : THYROID GLAND : ALTERATION, COLLOID, mild. No Microscopic Abnormality Observed : NOSE, MANDIBLE 643318 Terminal Sacrifice Killed on Day : 91 Exposure Group : 90-DAY EXPOSURE Animal is signed off from necropsy Gross Pathology : No Macroscopic Abnormality Observed : LIVER,.KIDNEYS, LUNGS, HEART, SKELETAL MUSCLE, SPLEEN, AORTA, BRAIN, SPINAL CORD, STOMACH, DUODENUM, JEJUNUM, ILEUM, PANCREAS, CECUM, COLON, RECTUM, MESENTERIC LYMPH NODE, SALIVARY GLANDS, MANDIBULAR LYMPH NODE, THYMUS, ADRENAL GLANDS, SCIATIC NERVE, PITUITARY GLAND, THYROID GLAND, PARATHYROID GLANDS, TRACHEA, ESOPHAGUS, PHARYNX/LARYNX, EYE(S) WITH OPTIC NERVE, SKIN, PROSTATE, SEMINAL VESICLES, URINARY BLADDER, TESTES, EPIDIDYMIDES, FEMUR/KNEE JOINT, STERNUM, NOSE, MANDIBLE Histopathology : 643318 LIVER : INFLAMMATION, SUBACUTE/CHRONIC, minimal. HYPERTROPHY, HEPATOCYTE, CENTRILOBULAR, minimal. Continued on the next page .... 933 Company Sanitized. Does not co 0 H-24516: Subchronic Toxicity 90-Day Gavage Study in Rats with One-Generation Reproduction Evaluations INDIVIDUAL ANIMAL GROSS AND MICROSCOPIC OBSERVATIONS Dose Group : V - 100 mg/kg/day Sex: Males Animal Ref Microscopic & Macroscopic Findings 643318 Continued from previous page Histopathology : LIVER : FATTY CHANGE, CENTRILOBULAR,.minimal. THYROID GLAND : ALTERATION, COLLOID, minimal. HYPERTROPHY, FOLLICULAR, minimal. NOSE : DEGENERATION, AMELOBLASTS, minimal. No Microscopic Abnormality Observed : KIDNEYS, MANDIBLE 934 Company Sanitized. Does not A \^ H H-24516: Subchronic Toxicity 90-Day Gavage Study in Rats with One-Generation Reproduction Evaluations INDIVIDUAL AMIMAL GROSS AND MICROSCOPIC OBSERVATIONS Dose Group Animal Ref : VII - 250 mg/kg/day Sex: Males Microscopic & Macroscopic Findings 643149 Terminal Sacrifice Killed on Day : 181 Exposure Group : THREE-MONTH RECOVERY Animal is signed off from necropsy Gross Pathology : No Macroscopic Abnormality Observed : LIVER, KIDNEYS, LUNGS, HEART, SKELETAL MUSCLE, SPLEEN, AORTA, BRAIN, SPINAL CORD, STOMACH, DUODENUM, JEJUNUM, ILEUM, PANCREAS, CECUM, COLON, RECTUM, MESENTERIC LYMPH NODE, SALIVARY GLANDS, MANDIBULAR LYMPH NODE, THYMUS, ADRENAL GLANDS, SCIATIC NERVE, PITUITARY GLAND, THYROID GLAND, PARATHYROID GLANDS, TRACHEA, ESOPHAGUS, "-PHARYNX/LARYNX, EYE(S) WITH OPTIC NERVE, SKIN, PROSTATE, SEMINAL VESICLES, URINARY BLADDER, TESTES, EPIDIDYMIDES, FEMUR/KNEE JOINT, STERNUM, NOSE, MANDIBLE Histopathology : LIVER : INFLAMMATION, SUBACUTE/CHRONIC, minimal. FATTY CHANGE, MEDIAN CLEFT, mild. . KIDNEYS : CALCULUS\CALCULI, minimal. HYPERPLASIA, TRANSITIONAL CELL, INFLAMMATION, SUBACUTE/CHRONIC, THYROID GLAND : minimal. minimal. ALTERATION, COLLOID, severe. NOSE : INFLAMMATION, SUBACUTE/CHRONIC, minimal. HYPERPLASIA/SQUAMOUS METAPLASIA, RESPIRATORY, EPITHELIUM, minimal. 935 Company Sanitized. Does n  1 H-24516: Subchronic Toxicity 90-Day Gavage Study in Rats with One-Generation Reproduction Evaluations INDIVIDUAL ANIMAL GROSS AND MICROSCOPIC OBSERVATIONS Dose Group : VII - 250 mg/kg/day Sex: Males Animal Ref Microscopic & Macroscopic Findings 643151 Terminal Sacrifice Killed on Day : 125 Exposure Group : ONE-MONTH RECOVERY Animal is signed off from necropsy Gross Pathology : No Macroscopic Abnormality Observed : LIVER, KIDNEYS, LUNGS, HEART, SKELETAL MUSCLE, SPLEEN, AORTA, BRAIN, SPINAL CORD, STOMACH, DUODENUM, JEJUNUM, ILEUM, PANCREAS, CECUM, COLON, RECTUM, MESENTERIC LYMPH NODE, SALIVARY GLANDS, MANDIBULAR LYMPH MODE, THYMUS, ADRENAL GLANDS, SCIATIC NERVE, PITUITARY GLAND, THYROID GLAND, PARATHYROID GLANDS, TRACHEA, ESOPHAGUS, ""PHARYNX/LARYNX, EYE(S) WITH OPTIC NERVE, SKIN, PROSTATE, SEMINAL VESICLES, URINARY BLADDER, TESTES, EPIDIDYMIDES, FEMUR/KNEE JOINT, STERNUM, NOSE, MANDIBLE Histopathology : LIVER : INFLAMMATION, SUBACUTE/CHRONIC, minimal. HYPERTROPHY, HEPATOCYTE, CENTRILOBULAR, mild. FOCUS OP CELLULAR ALTERATION, BASOPHILIC, minimal. KIDNEYS : HYPERTROPHY, TUBULAR, minimal. THYROID GLAND : ALTERATION, COLLOID, mild. NOSE : DEGENERATION, AMELOBLASTS, minimal. No Microscopic Abnormality Observed : MANDIBLE 936 Company Sanitized. Does not conta H-24516: Subchronic Toxicity 90-Day Gavage Study in Rats with One-Generation Reproduction Evaluations INDIVIDUAL ANIMAL GROSS AND MICROSCOPIC OBSERVATIONS Dose Group : VII - 250 mg/kg/day Sex: Males Animal Ref Microscopic & Macroscopic Findings 643152 Terminal Sacrifice Killed on Day : 181 Exposure Group : THREE-MONTH RECOVERY Animal is signed off from necropsy Gross Pathology : No Macroscopic Abnormality Observed : LIVER, KIDNEYS, LUNGS, HEART, SKELETAL MUSCLE, SPLEEN, AORTA, BRAIN, SPINAL CORD, STOMACH, DUODENUM, JEJUNUM, ILEUM, PANCREAS. CECUM, COLON, RECTUM, MESENTERIC LYMPH NODE, SALIVARY GLANDS, MANDIBULAR LYMPH NODE, THYMUS, ADRENAL GLANDS, SCIATIC NERVE, PITUITARY GLAND, THYROID GLAND, PARATHYROID GLANDS, TRACHEA, ESOPHAGUS, ""PHARYNX/LARYNX, EYE(S) WITH OPTIC NERVE, SKIN, PROSTATE, SEMINAL VESICLES, URINARY BLADDER, TESTES, EPIDIDYMIDES, FEMUR/KNEE JOINT, STERNUM, NOSE, MANDIBLE Histopathology : LIVER : ' INFLAMMATION, SUBACUTE/CHRONIC, minimal. HYPERTROPHY, HEPATOCYTE, CENTRILOBULAR, minimal. KIDNEYS : NEPHROPATHY, CHRONIC PROGRESSIVE, moderate. THYROID GLAND : ALTERATION, COLLOID, moderate. NOSE : DEGENERATION, AMELOBLASTS, mild. 937 Company Sanitized. Does not c  H-24516: Subchronic Toxicity 90-Day Gavage Study in Rats with One-Generation Reproduction Evaluations INDIVIDUAL ANIMAL GROSS AND MICROSCOPIC OBSERVATIONS Dose Group : VII - 250. mg/kg/day Sex: Males Animal Ref Microscopic & Macroscopic Findings 643165 . . Terminal Sacrifice Killed on Day : 125 Exposure Group : ONE-MONTH RECOVERY Animal is signed off from necropsy Gross Pathology : No Macroscopic Abnormality Observed : LIVER, KIDNEYS, LUNGS, HEART, SKELETAL MUSCLE, SPLEEN, AORTA, BRAIN, SPINAL CORD, STOMACH, DUODENUM, JEJUNUM, ILEUM, PANCREAS, CECUM, COLON, RECTUM, MESENTERIC LYMPH NODE, SALIVARY GLANDS, MANDIBULAR LYMPH NODE, THYMUS, ADRENAL GLANDS, SCIATIC NERVE, PITUITARY GLAND, THYROID GLAND, PARATHYROID GLANDS, TRACHEA, ESOPHAGUS, -PHARYNX/LARYNX, EYE(S) WITH OPTIC NERVE, SKIN, PROSTATE, SEMINAL VESICLES, URINARY BLADDER, TESTES, EPIDIDYMIDES, FEMUR/KMEE JOINT, STERNUM, NOSE, MANDIBLE Histopathology : LIVER : INFLAMMATION, SUBACUTE/CHRONIC, minimal. HYPERTROPHY, HEPATOCYTE, CENTRILOBULAR, minimal. THYROID GLAND : ALTERATION, COLLOID, mild. NOSE : DEGENERATION, AMELOBLASTS, minimal. No Microscopic Abnormality Observed : KIDNEYS, MANDIBLE 938 a^ny sa^ed. Doe, nolconto 1; . H-24516: Subchronic Toxicity 90-Day Gavage Study in Rats with One-Generation Reproduction Evaluations INDIVIDUAL ANIMAL GROSS AND MICROSCOPIC OBSERVATIONS Dose Group : VII - 250. mg/kg/day Sex: Males Animal Ref Microscopic & Macroscopic Findings 643174 Terminal Sacrifice Killed on Day : 91 Exposure Group : 90-DAY EXPOSURE Animal is signed off from necropsy Gross Pathology : No Macroscopic Abnormality Observed : LIVER, KIDNEYS, LUNGS, HEART, SKELETAL MUSCLE, SPLEEN, AORTA, BRAIN, SPINAL CORD, STOMACH, DUODENUM, JEJUNUM, ILEUM, PANCREAS, CECUM, COLON, RECTUM, MESENTERIC LYMPH NODE, SALIVARY GLANDS, MANDIBULAR LYMPH NODE, THYMUS, ADRENAL GLANDS, SCIATIC NERVE, PITUITARY GLAND, THYROID GLAND, PARATHYROID GLANDS, TRACHEA, ESOPHAGUS, " "PHARYNX/LARYNX, EYE(S) WITH OPTIC NERVE, SKIN, PROSTATE, SEMINAL VESICLES, URINARY BLADDER, TESTES, EPIDIDYMIDES, FEMUR/KNEE JOINT, STERNUM, NOSE, MANDIBLE Histopathology : 643174 LIVER : HYPERTROPHY, HEPATOCYTE, CENTRILOBULAR, FATTY CHANGE, INFLAMMATION, KIDNEYS : CENTRILOBULAR, minimal. SUBACUTE/CHRONIC, minimal. HYDRONEPHROSIS, BILATERAL, minimal. HYPERTROPHY, TUBULAR, mild. THYROID GLAND : ALTERATION, COLLOID, moderate. HYPERTROPHY, FOLLICULAR, mild. NOSE : DEGENERATION, AMELOBLASTS, mild. Continued on the next page .... mild. 939 Company Sanded. Does not con H-24516: Subchronic Toxicity 90-Day Gavage Study in Rats with One-Generation Reproduction Evaluations INDIVIDUAL ANIMAL GROSS AMD MICROSCOPIC OBSERVATIONS Dose Group Animal Ref : VII - 250 mg/kg/day Sex: Males Microscopic & Macroscopic Findings 643174 Continued from previous page Histopathology : MANDIBLE : DEGENERATION, AMELOBLASTS, mild. No Microscopic Abnormality Observed : LUNGS, HEART, SKELETAL MUSCLE, SPLEEN, AORTA, BRAIN, SPINAL CORD, STOMACH, DUODENUM, JEJUNUM, ILEUM, PANCREAS, CECUM, COLON, RECTUM, MESENTERIC LYMPH NODE, SALIVARY GLANDS, MANDIBULAR LYMPH NODE, THYMUS, ADRENAL GLANDS, SCIATIC NERVE, PITUITARY GLAND, PARATHYROID GLANDS, TRACHEA, ESOPHAGUS, PHARYNX/LARYNX, EYE(S) WITH OPTIC NERVE, SKIN, ""PROSTATE, SEMINAL VESICLES, URINARY BLADDER, TESTES, EPIDIDYMIDES, FEMUR/KNEE JOINT, STERNUM, BONE MARROW 643178 Terminal Sacrifice Killed on Day : 181 Exposure Group : THREE-MONTH RECOVERY Animal is signed off from necropsy Gross Pathology : No Macroscopic Abnormality Observed : LIVER, KIDNEYS, LUNGS, HEART, SKELETAL MUSCLE, SPLEEN, AORTA, BRAIN, SPINAL CORD, STOMACH, DUODENUM, JEJUNUM, ILEUM, PANCREAS, CECUM, COLON, RECTUM, MESENTERIC LYMPH NODE, SALIVARY GLANDS, MANDIBULAR LYMPH NODE, THYMUS, ADRENAL GLANDS, SCIATIC NERVE, PITUITARY GLAND, 643178 Continued on the next page .... 940 Company Sanitized. Does not con H-24516: Subchronic Toxicity 90-Day Gavage Study in Rats with One-Generation Reproduction Evaluations INDIVIDUAL ANIMAL GROSS AND MICROSCOPIC OBSERVATIONS Dose Group : VII - 250 mg/kg/day Sex: Males Animal Ref Microscopic & Macroscopic Findings 643178 Continued from previous page Gross Pathology : No Macroscopic Abnormality Observed : THYROID GLAND, PARATHYROID GLANDS, TRACHEA, ESOPHAGUS, PHARYNX/LARYNX, EYE(S) WITH OPTIC NERVE, SKIN, PROSTATE, SEMINAL VESICLES, URINARY BLADDER, TESTES, EPIDIDYMIDES, FEMUR/KNEE JOINT, STERNUM, NOSE, MANDIBLE Histopathology : LIVER : INFLAMMATION. SUBACUTE/CHRONIC, minimal. KIDNEYS : - NEPHROPATHY, CHRONIC PROGRESSIVE, minimal. THYROID GLAND : ALTERATION, COLLOID, severe. NOSE : INFLAMMATION, SUBACUTE/CHRONIC, minimal. HYPERPLASIA/HYPERTROPHY, TRANSITIONAL CELL, minimal. EPITHELIUM, 643193 Terminal Sacrifice Killed on Day : 91 Exposure Group : 90-DAY EXPOSURE Animal is signed off from necropsy Gross Pathology : 643193 No Macroscopic Abnormality Observed : LIVER, KIDNEYS, LUNGS, HEART, SKELETAL MUSCLE, SPLEEN, AORTA, BRAIN, SPINAL CORD, STOMACH, DUODENUM, JEJUNUM, ILEUM, PANCREAS, CECUM, COLON, RECTUM, MESENTERIC LYMPH NODE, SALIVARY GLANDS. MANDIBULAR LYMPH NODE, THYMUS, ADRENAL GLANDS, SCIATIC NERVE, PITUITARY GLAND, Continued on the next page .... 941 Company SanHIzed. Does not  H-24516: Subchronic Toxicity 90-Day Gavage Study in Rats with One-Generation Reproduction Evaluations INDIVIDUAL ANIMAL GROSS AND MICROSCOPIC OBSERVATIONS Dose Group : VII - 250 mg/kg/day Sex: Males Animal Ref Microscopic & Macroscopic Findings 643193 Continued from previous page Gross Pathology : No Macroscopic Abnormality Observed : THYROID GLAND, PARATHYROID GLANDS, TRACHEA, ESOPHAGUS, PHARYNX/LARYNX, EYE(S) WITH OPTIC NERVE, SKIN, PROSTATE, SEMINAL VESICLES, URINARY BLADDER, TESTES, EPIDIDYMIDES, FEMUR/KNEE JOINT, STERNUM, NOSE, MANDIBLE Histopathology : LIVER : ..INFLAMMATION, SUBACUTE/CHRONIC, minimal. HYPERTROPHY, HEPATOCYTE, CENTRILOBULAR, mild. KIDNEYS : NEPHROPATHY, HYPERTROPHY, LUNGS : CHRONIC PROGRESSIVE, TUBULAR, minimal. minimal. INFLAMMATION, GRANULOMATOUS, minimal. THYROID GLAND : ALTERATION, COLLOID, moderate. HYPERTROPHY, FOLLICULAR, mild. EYE(S) WITH OPTIC NERVE : FOLD/ROSETTE, RETINAL, minimal. NOSE : DEGENERATION, AMELOBLASTS, mild. MANDIBLE : DEGENERATION, AMELOBLASTS, mild. 643193 Continued on the next page .... "9426ompany Sanitized. Poes no '&. ^ H-24516: Subchronic Toxicity 90-Day Gavage Study in Rats with One-Generation Reproduction Evaluations INDIVIDUAL ANIMAL GROSS AND MICROSCOPIC OBSERVATIONS Dose Group : VII - Animal Ref 643193 250 mg/kg/day Sex: Males Microscopic & Macroscopic Findings Continued from previous page Histopathology : No Microscopic Abnormality Observed : HEART, SKELETAL MUSCLE, SPLEEM, AORTA, BRAIN, SPINAL CORD, STOMACH, DUODENUM, JEJUNUM, ILEUM, PANCREAS, CECUM, COLON, RECTUM, MESENTERIC LYMPH NODE, SALIVARY GLANDS, MANDIBULAR LYMPH NODE, THYMUS, ADRENAL GLANDS, SCIATIC NERVE, PITUITARY GLAND, PARATHYROID GLANDS, TRACHEA, ESOPHAGUS, PHARYNX/LARYNX, SKIN, PROSTATE, SEMINAL VESICLES, URINARY BLADDER, TESTES, EPIDIDYMIDES, FEMUR/KNEE JOINT, STERNUM, BONE MARROW 643194 - Terminal Sacrifice Killed on Day : 91 Exposure Group : 90-DAY EXPOSURE Animal is signed off from necropsy Gross Pathology : No Macroscopic Abnormality observed : LIVER, KIDNEYS, LUNGS, HEART, SKELETAL MUSCLE, SPLEEN, AORTA, BRAIN, SPINAL CORD, STOMACH, DUODENUM, JEJUNUM, ILEUM, PANCREAS, CECUM, COLON, RECTUM, MESENTERIC LYMPH NODE, SALIVARY GLANDS, MANDIBULAR LYMPH NODE, THYMUS, ADRENAL GLANDS, SCIATIC NERVE, PITUITARY GLAND, THYROID GLAND, PARATHYROID GLANDS, TRACHEA, ESOPHAGUS, PHARYNX/LARYMX, EYE(S) WITH OPTIC NERVE, SKIN, PROSTATE, SEMINAL VESICLES, URINARY BLADDER, TESTES, EPIDIDYMIDES, FEMUR/KNEE JOINT, STERNUM, NOSE, MANDIBLE 643194 Continued on the next page .... 943 tc  H-24516: Subchronic Toxicity 90-Day Gavage Study in Rats with One-Generation Reproduction Evaluations INDIVIDUAL ANIMAL GROSS AND MICROSCOPIC OBSERVATIONS Dose Group : VII - Animal Ref 250 mg/kg/day Sex: Males Microscopic & Macroscopic Findings 643194 Continued from previous page Histopathology : LIVER : INFLAMMATION, SUBACUTE/CHRONIC, minimal. HYPERTROPHY, HEPATOCYTE, CENTRILOBULAR, mild. KIDNEYS : NEPHROPATHY, HYPERTROPHY, HEART : CHRONIC PROGRESSIVE, TUBULAR, mild. minimal. CARDIOMYOPATHY, minimal. THYROID GLAND : .ALTERATION, COLLOID, severe. - HYPERTROPHY, FOLLICULAR, mild. NOSE : DEGENERATION, AMELOBLASTS, mild. MANDIBLE : DEGENERATION, AMELOBLASTS, minimal. No Microscopic Abnormality Observed : LUNGS, SKELETAL MUSCLE, SPLEEN, AORTA, BRAIN, SPINAL CORD, STOMACH, DUODENUM, JEJUNUM, ILEUM, PANCREAS, CECUM, COLON, RECTUM, MESENTERIC LYMPH NODE, SALIVARY GLANDS, MANDIBULAR LYMPH NODE, THYMUS, ADRENAL GLANDS, SCIATIC NERVE, PITUITARY GLAND, PARATHYROID GLANDS, TRACHEA, ESOPHAGUS, PHARYNX/LARYNX, EYE(S) WITH OPTIC NERVE, SKIN, PROSTATE, SEMINAL VESICLES, URINARY BLADDER, TESTES, EPIDIDYMIDES, FEMUR/KNEE JOINT, STERNUM, BONE MARROW 944 Company Sanitized. Does not c H-24516: Subchronic Toxicity 90-Day Gavage Study in Rats with One-Generation Reproduction Evaluations INDIVIDUAL ANIMAL GROSS AND MICROSCOPIC OBSERVATIONS Dose Group : VII - 250 nig/kg/day Sex: Males Animal Ref Microscopic & Macroscopic Findings 643201 Terminal Sacrifice Killed on Day : 91 Exposure Group : 90-DAY EXPOSURE Animal is signed off from necropsy Gross Pathology : No Macroscopic Abnormality Observed : LIVER, KIDNEYS, LUNGS, HEART. SKELETAL MUSCLE, SPLEEN, AORTA, BRAIN, SPINAL CORD, STOMACH, DUODENUM, JEJUNUM, ILEUM, PANCREAS, CECUM, COLON, RECTUM, MESENTERIC LYMPH NODE, SALIVARY GLANDS, MANDIBULAR LYMPH NODE, THYMUS, ADRENAL GLANDS, SCIATIC NERVE, PITUITARY GLAND, THYROID GLAND, PARATHYROID GLANDS, TRACHEA, ESOPHAGUS, "PHARYNX/LARYNX, EYE(S) WITH OPTIC NERVE, SKIN, PROSTATE, SEMINAL VESICLES, URINARY BLADDER, TESTES, EPIDIDYMIDES, FEMUR/KNEE JOINT, STERNUM, NOSE, MANDIBLE Histopathology : 643201 LIVER : INFLAMMATION, SUBACUTE/CHRONIC, minimal. HYPERTROPHY, HEPATOCYTE, CENTRILOBULAR, moderate. KIDNEYS : HYPERTROPHY, TUBULAR, mild. THYROID GLAND : ALTERATION, COLLOID, moderate. HYPERTROPHY, FOLLICULAR, minimal. NOSE : INFLAMMATION, SUBACUTE/CHRONIC, minimal. DEGENERATION, AMELOBLASTS, mild. MANDIBLE : .... DEGENERATION, AMELOBLASTS, mild. Continued on the next page 945 ^n^ S-W-- "^ wrf cnnw" H-24516: Subchronic Toxicity 90-Day Gavage Study in Rats with One-Generation Reproduction Evaluations INDIVIDUAL ANIMAL GROSS AND MICROSCOPIC OBSERVATIONS Dose Group : VII - Animal Ref 250 mg/kg/day Sex: Males Microscopic & Macroscopic Findings 643201 Continued from previous page Histopathology : No Microscopic Abnormality Observed : LUNGS, HEART, SKELETAL MUSCLE, SPLEEN, AORTA, BRAIN, SPINAL CORD, STOMACH, DUODENUM, JEJUNUM, ILEUM, PANCREAS, CECUM, COLON, RECTUM, MESENTERIC LYMPH NODE, SALIVARY GLANDS, MANDIBULAR LYMPH NODE, THYMUS, ADRENAL GLANDS, SCIATIC NERVE, PITUITARY GLAND, PARATHYROID GLANDS, TRACHEA, ESOPHAGUS, PHARYNX/LARYNX, EYE(S) WITH OPTIC NERVE, SKIN, PROSTATE, SEMINAL VESICLES, URINARY BLADDER. TESTES, EPIDIDYMIDES, FEMUR/KNEE JOINT, STERNUM, BONE MARROW 643215 " Terminal Sacrifice Killed on Day : 91 Exposure Group : 90-DAY EXPOSURE Animal is signed off from necropsy Gross Pathology : No Macroscopic Abnormality Observed : LIVER, KIDNEYS, LUNGS, HEART. SKELETAL MUSCLE, SPLEEN, AORTA, BRAIN, SPINAL CORD, STOMACH, DUODENUM, JEJUNUM, ILEUM, PANCREAS, CECUM, COLON, RECTUM, MESENTERIC LYMPH NODE, SALIVARY GLANDS, MANDIBULAR LYMPH NODE, THYMUS, ADRENAL GLANDS, SCIATIC NERVE, PITUITARY GLAND, THYROID GLAND, PARATHYROID GLANDS, TRACHEA, ESOPHAGUS, PHARYNX/LARYNX, EYE(S) WITH OPTIC NERVE, SKIN, PROSTATE, SEMINAL VESICLES, URINARY BLADDER, TESTES, EPIDIDYMIDES, FEMUR/KNEE JOINT, STERNUM, NOSE, MANDIBLE 643215 Continued on the next page .... 946 Company Sanitized. Doe not co A H H-24516: Subchronic Toxicity 90-Day Gavage Study in Rats with One-Generation Reproduction Evaluations INDIVIDUAL ANIMAL GROSS AND MICROSCOPIC OBSERVATIONS Dose Group Animal Ref : VII - 250 mg/kg/day Sex: Males Microscopic & Macroscopic Findings 643215 Continued from previous page Histopathology : LIVER : INFLAMMATION, SUBACUTE/CHRONIC, minimal. HYPERTROPHY, HEPATOCYTE, CENTRILOBULAR, mild. KIDNEYS : NEPHROPATHY, HYPERTROPHY, THYROID GLAND : CHRONIC PROGRESSIVE, TUBULAR, mild. mild. ALTERATION, COLLOID, mild. NOSE : DEGENERATION, AMELOBLASTS, mild. MANDIBLE : DEGENERATION, AMELOBLASTS, mild. No Microscopic Abnormality Observed : LUNGS, HEART, SKELETAL MUSCLE, SPLEEN, AORTA, BRAIN, SPINAL CORD, STOMACH, DUODENUM, JEJUNUM, ILEUM, PANCREAS, CECUM, COLON, RECTUM, MESENTERIC LYMPH NODE, SALIVARY GLANDS, MANDIBULAR LYMPH NODE, THYMUS, ADRENAL GLANDS, SCIATIC NERVE, PITUITARY GLAND, PARATHYROID GLANDS, TRACHEA, ESOPHAGUS, PHARYNX/LARYNX, EYE(S) WITH OPTIC NERVE, SKIN, PROSTATE, SEMINAL VESICLES, URINARY BLADDER, TESTES, EPIDIDYMIDES, PEMUR/KMEE JOINT, STERNUM, BONE MARROW 947 Company Sanitized. Does not con H-24516: Subchronic Toxicity 90-Day Gavage Study in Rats with One-Generation Reproduction Evaluations INDIVIDUAL ANIMAL GROSS AND MICROSCOPIC OBSERVATIONS Dose Group : VII - 250 mg/kg/day Sex: Males Animal Ref Microscopic & Macroscopic Findings 643220 Terminal Sacrifice Killed on Day : 125 Exposure Group : ONE-MONTH RECOVERY Animal is signed off from necropsy Gross Pathology : SEMINAL VESICLES : SMALL, LEFT. TESTES : SOFT, BILATERAL. EPIDIDYMIDES : DEFORMITY, LEFT. No"Macroscopic Abnormality Observed : LIVER, KIDNEYS,. LUNGS, HEART, SKELETAL MUSCLE, SPLEEN, AORTA, BRAIN, SPINAL CORD, STOMACH, DUODENUM, JEJUNUM, ILEUM, PANCREAS, CECUM, COLON, RECTUM, MESENTERIC LYMPH NODE, SALIVARY GLANDS, MANDIBULAR LYMPH NODE, THYMUS, ADRENAL GLANDS, SCIATIC NERVE, PITUITARY GLAND, THYROID GLAND, PARATHYROID GLANDS, TRACHEA, ESOPHAGUS, PHARYNX/LARYNX, EYE(S) WITH OPTIC NERVE, SKIN, PROSTATE, URINARY BLADDER, FEMUR/KNEE JOINT, STERNUM, NOSE, MANDIBLE Histopathology : LIVER : INFLAMMATION, SUBACUTE/CHRONIC, minimal. HYPERTROPHY, HEPATOCYTE, CENTRILOBULAR, minimal. THYROID GLAND : ALTERATION, COLLOID, mild. 643220 Continued on the next page..... 948 Company Sanitized. Does not con H-24516: Subchronic Toxicity 90-Day Gavage Study in Rats with One-Generation Reproduction Evaluations INDIVIDUAL ANIMAL GROSS AND MICROSCOPIC OBSERVATIONS Dose Group : VII - Animal Ref 250. nig/kg/day Sex: Males Microscopic & Macroscopic Findings 643220 Continued from previous page Histopathology : TESTES : DEGENERATION/ATROPHY, SEMINIFEROUS TUBULES, BILATERAL, moderate. EPIDIDYMIDES : OLIGOSPERMIA/GERM CELL DEBRIS, UNILATERAL, moderate. NOSE : DEGENERATION, AMELOBLASTS, minimal. No Microscopic Abnormality Observed : KIDNEYS, SEMINAL VESICLES, MANDIBLE 643225 Terminal Sacrifice Killed on Day : 125 Exposure Group : ONE-MONTH RECOVERY Animalis signed off from necropsy Gross Pathology : 643225 No Macroscopic Abnormality Observed : LIVER, KIDNEYS, LUNGS, HEART, SKELETAL MUSCLE, SPLEEN, AORTA, BRAIN, SPINAL CORD, STOMACH, DUODENUM, JEJUNUM, ILEUM, PANCREAS, CECUM, COLON, RECTUM, MESENTERIC LYMPH NODE, SALIVARY GLANDS, MANDIBULAR LYMPH NODE, THYMUS, ADRENAL GLANDS, SCIATIC NERVE, PITUITARY GLAND, THYROID GLAMD, PARATHYROID GLANDS, TRACHEA, ESOPHAGUS, PHARYNX/LARYNX, EYE(S) WITH OPTIC NERVE, SKIN, PROSTATE, SEMINAL VESICLES, URINARY BLADDER, TESTES, EPIDIDYMIDES, FEMUR/KNEE JOINT, STERNUM, NOSE, MANDIBLE Continued on the next page .... 949 Company Sanitized. Does not con  H-24516: Subchronic Toxicity 90-Day Gavage Study in Rats with One-Generation Reproduction Evaluations INDIVIDUAL ANIMAL GROSS AND MICROSCOPIC OBSERVATIONS Dose Group Animal Ref : VII - 250 mg/kg/day Sex: Males Microscopic & Macroscopic Findings 643225 Continued from previous page Histopathology : LIVER : INFLAMMATION, SUBACUTE/CHRONIC, minimal. HYPERTROPHY, HEPATOCYTE, CENTRILOBULAR, mild. THYROID GLAND : ALTERATION, COLLOID, moderate. NOSE : DEGENERATION, AMELOBLASTS, mild. No Microscopic Abnormality Observed : KIDNEYS, MANDIBLE 643234 Terminal Sacrifice Killed on Day : 125 Exposure Group : ONE-MONTH RECOVERY Animal .i-s signed off from necropsy Gross Pathology : 643234 No Macroscopic Abnormality Observed : LIVER, KIDNEYS, LUNGS, HEART, SKELETAL MUSCLE, SPLEEN, AORTA, BRAIN, SPINAL CORD, STOMACH, DUODENUM, JEJUNUM, ILEUM, PANCREAS, CECUM, COLON, RECTUM, MESENTERIC LYMPH NODE, SALIVARY GLANDS, MANDIBULAR LYMPH NODE, THYMUS, ADRENAL GLANDS, SCIATIC NERVE, PITUITARY GLAND, THYROID GLAND, PARATHYROID GLANDS, TRACHEA, ESOPHAGUS, PHARYNX/LARYNX, EYE(S) WITH OPTIC NERVE, SKIN, PROSTATE, SEMINAL VESICLES, URINARY BLADDER, TESTES, EPIDIDYMIDES, FEMUR/KNEE JOINT, STERNUM, NOSE, MANDIBLE Continued on the next page .... 950 Company Sanitized. Does not contai H-24516: Subchronic Toxicity 90-Day Gavage Study in Rats with One-Generation Reproduction Evaluations INDIVIDUAL ANIMAL GROSS AND MICROSCOPIC OBSERVATIONS Dose Group : VII - 250 ing/kg/day Sex: Males Animal Ref Microscopic & Macroscopic Findings 643234 Continued from previous page Histopathology : LIVER : INFLAMMATION, SUBACUTE/CHRONIC, minimal. HYPERTROPHY, HEPATOCYTE, CENTRILOBULAR, mild. KIDNEYS : HYDRONEPHROSIS, UNILATERAL, minimal. NEPHROPATHY, CHRONIC PROGRESSIVE, minimal. THYROID GLAND : ALTERATION, COLLOID, severe. NOSE : DEGENERATION, AMELOBLASTS, minimal. No Microscopic Abnormality Observed : MANDIBLE 643236 Terminal Sacrifice Killed on Day : 125 Exposure Group : ONE-MONTH RECOVERY Animal is signed off from necropsy Gross Pathology : THYMUS : SMALL. 643236 Continued on the next page .... Company Sanitised. Doe not c H-24516: Subchronic Toxicity 90-Day Gavage Study in Rats with One-Generation Reproduction Evaluations INDIVIDUAL ANIMAL GROSS AND MICROSCOPIC OBSERVATIONS Dose Group : VII - 250. mg/kg/day Sex: Males Animal Ref Microscopic & Macroscopic Findings 643236 Continued from previous page Gross Pathology : No Macroscopic Abnormality Observed : LIVER, KIDNEYS, LUNGS, HEART, SKELETAL MUSCLE, SPLEEN, AORTA, BRAIN, SPINAL CORD, STOMACH, DUODENUM, JEJUNUM, ILEUM, PANCREAS, CECUM, COLON, RECTUM, MESENTERIC LYMPH NODE, SALIVARY GLANDS, MANDIBULAR LYMPH NODE, ADRENAL GLANDS, SCIATIC NERVE, PITUITARY GLAND, THYROID GLAND, PARATHYROID GLANDS, TRACHEA, ESOPHAGUS, PHARYNX/LARYNX, EYE(S) WITH OPTIC NERVE, SKIN, PROSTATE, SEMINAL VESICLES, URINARY BLADDER, TESTES, EPIDIDYMIDES, FEMUR/KNEE JOINT, STERNUM, NOSE, MANDIBLE Histopathology : LIVER : INFLAMMATION, SUBACUTE/CHRONIC, minimal. HYPERTROPHY, HEPATOCYTE, CENTRILOBULAR, minimal. KIDNEYS : NEPHROPATHY, CHRONIC PROGRESSIVE, minimal. THYROID GLAND : ALTERATION, COLLOID, moderate. NOSE : DEGENERATION, AMELOBLASTS, mild. No Microscopic Abnormality Observed : THYMUS, MANDIBLE 952 H-24516: Subchronic Toxicity 90-Day Gavage Study in Rats with One-Generation Reproduction Evaluations INDIVIDUAL ANIMAL GROSS AND MICROSCOPIC OBSERVATIONS Dose Group : VII - Animal Ref 643252 . 250 mg/kg/day Sex: Males Microscopic & Macroscopic Findings Terminal Sacrifice Killed on Day : 91 Exposure Group : 90-DAY EXPOSURE Animal is signed off from necropsy Gross Pathology : No Macroscopic Abnormality Observed : LIVER, KIDNEYS, LUNGS, HEART, SKELETAL MUSCLE, SPLEEN, AORTA, BRAIN, SPINAL CORD, STOMACH. DUODENUM, JEJUNUM, ILEUM. PANCREAS, CECUM, COLON. RECTUM, MESENTERIC LYMPH NODE, SALIVARY GLANDS, MANDIBULAR LYMPH NODE, THYMUS, ADRENAL GLANDS, SCIATIC NERVE, PITUITARY GLAND, THYROID GLAND, PARATHYROID GLANDS, TRACHEA, ESOPHAGUS. "PHARYNX/LARYNX, EYE(S) WITH OPTIC NERVE, SKIM, PROSTATE, SEMINAL VESICLES, URINARY BLADDER, TESTES, EPIDIDYMIDES, FEMUR/KNEE JOINT, STERNUM, NOSE, MANDIBLE Histopathology : 643252 LIVER : INFLAMMATION, SUBACUTE/CHRONIC, minimal. HYPERTROPHY, HEPATOCYTE, CENTRILOBULAR, mild. KIDNEYS : NEPHROPATHY, HYPERTROPHY, PANCREAS : CHRONIC PROGRESSIVE, TUBULAR, mild. minimal. INFLAMMATION, SUBACUTE/CHRONIC, minimal. THYROID GLAND : ALTERATION, COLLOID, moderate. HYPERTROPHY, FOLLICULAR, mild. EYE(S) WITH OPTIC NERVE : OPTIC NERVE NOT PRESENT. Continued on the next page .... 953 Company SanBlzeA Does not contain T  H-24516: Subchronic Toxicity 90-Day Gavage Study in Rats with One-Generation Reproduction Evaluations INDIVIDUAL ANIMAL GROSS AND MICROSCOPIC OBSERVATIONS Dose Group : VII - Animal Ref 250 ing/kg/day Sex: Males Microscopic & Macroscopic Findings 643252 . Continued from previous page Histopathology : NOSE : DEGENERATION, MANDIBLE : DEGENERATION, AMELOBLASTS, AMELOBLASTS, mild. mild. No Microscopic Abnormality Observed : LUNGS, HEART, SKELETAL MUSCLE, SPLEEN, AORTA, BRAIN, SPINAL CORD, STOMACH, DUODENUM, JEJUNUM, ILEUM, CECUM, COLON, RECTUM, MESENTERIC LYMPH NODE, SALIVARY GLANDS, MANDIBULAR LYMPH NODE, THYMUS, ADRENAL GLANDS, SCIATIC NERVE, ""PITUITARY GLAND, PARATHYROID GLANDS, TRACHEA, ESOPHAGUS, PHARYNX/LARYNX, EYE(S) WITH OPTIC NERVE, SKIN, PROSTATE, SEMINAL VESICLES, URINARY BLADDER, TESTES, EPIDIDYMIDES, FEMUR/KNEE JOINT, STERNUM, BONE MARROW 643258 Terminal Sacrifice Killed on Day : 125 Exposure Group : ONE-MONTH RECOVERY Animal is signed off from necropsy Gross Pathology : 643258 No Macroscopic Abnormality Observed : LIVER, KIDNEYS, LUNGS, HEART, SKELETAL MUSCLE, SPLEEN, AORTA, BRAIN, SPINAL CORD, STOMACH, DUODENUM, JEJUNUM, ILEUM, PANCREAS, CECUM, COLON, RECTUM, MESENTERIC LYMPH NODE, SALIVARY GLANDS, MANDIBULAR LYMPH NODE, THYMUS, ADRENAL GLANDS, SCIATIC NERVE, PITUITARY GLAND, Continued on the next page .... 954 Company Sanitized. Does not contain T A . ^ H-24516: Subchronic Toxicity 90-Day Gavage Study in Rats with One-Generation Reproduction Evaluations INDIVIDUAL ANIMAL GROSS AND MICROSCOPIC OBSERVATIONS Dose Group : VII - 250 mg/kg/day Sex: Males Animal Ref Microscopic & Macroscopic Findings 643258 Continued from previous page Gross Pathology : No Macroscopic Abnormality Observed : THYROID GLAND, PARATHYROID GLANDS, TRACHEA, ESOPHAGUS, PHARYNX/LARYNX, EYE(S) WITH OPTIC NERVE, SKIN, PROSTATE, SEMINAL VESICLES. URINARY BLADDER, TESTES, EPIDIDYMIDES, FEMUR/KNEE JOINT, STERNUM, NOSE. MANDIBLE Histopathology : LIVER : INFLAMMATION, SUBACUTE/CHRONIC, minimal. HYPERTROPHY, HEPATOCYTE, CENTRILOBULAR, mild. THYROID GLAND : ALTERATION, COLLOID, moderate. NOSE : DEGENERATION, AMELOBLASTS, mild. No Microscopic Abnormality Observed : KIDNEYS, MANDIBLE 643259 Terminal Sacrifice Killed on Day : 91 Exposure Group : 90-DAY EXPOSURE Animal is signed off from necropsy Gross Pathology : 643259 No Macroscopic Abnormality Observed : LIVER, KIDNEYS, LUNGS, HEART, SKELETAL MUSCLE, SPLEEN, AORTA, BRAIN, SPINAL CORD, STOMACH, DUODENUM, JEJUNUM, ILEUM, PANCREAS, CECUM, COLON, RECTUM, MESENTERIC LYMPH NODE, SALIVARY GLANDS, MANDIBULAR LYMPH NODE, THYMUS, ADRENAL GLANDS, SCIATIC NERVE, PITUITARY GLAND, Continued on the next page .... 955 c^.^^o--"'""-1"TM ^ 1 H-24516: Subchronic Toxicity 90-Day Gavage Study in Rats with One-Generation Reproduction Evaluations INDIVIDUAL ANIMAL GROSS AND MICROSCOPIC OBSERVATIONS Dose Group : VII - 250 mg/kg/day Sex: Males Animal Ref Microscopic & Macroscopic Findings Animal Ref . Microscopic & Macroscopic Findings 643259 Continued from previous page Gross Pathology : No Macroscopic Abnormality Observed : THYROID GLAND, PARATHYROID GLANDS, TRACHEA, ESOPHAGUS, PHARYNX/LARYNX, EYE(S) WITH OPTIC NERVE, SKIN, PROSTATE, SEMINAL VESICLES. URINARY BLADDER, TESTES, EPIDIDYMIDES, FEMUR/KNEE JOINT, STERNUM, NOSE, MANDIBLE Histopathology : 643259 LIVflR : INFLAMMATION, SUBACUTE/CHRONIC, minimal. HYPERTROPHY, HEPATOCYTE, CENTRILOBULAR, mild. FATTY CHANGE, CENTRILOBULAR, minimal. NECROSIS', FOCAL, minimal. KIDNEYS : HYDRONEPHROSIS, UNILATERAL, minimal. HYPERTROPHY, TUBULAR, minimal. HEART : CARDIOMYOPATHY, minimal. PANCREAS : ATROPHY, minimal. THYROID GLAND : ALTERATION, COLLOID, mild. HYPERTROPHY, FOLLICULAR, minimal. ESOPHAGUS : INFLAMMATION, SUBACUTE/CHRONIC, minimal. NOSE : DEGENERATION, AMELOBLASTS, mild. MANDIBLE : DEGENERATION, AMELOBLASTS, mild. Continued on the next page .... 956 Company Sanitized. Does not contai H-24516: Subchronic Toxicity 90-Day Gavage Study in Rats with One-Generation Reproduction Evaluations INDIVIDUAL ANIMAL GROSS AND MICROSCOPIC OBSERVATIONS Dose Group : VII - 250 nig/kg/day Sex: Males Animal Ref Microscopic & Macroscopic Findings 643259 . Continued from previous page Histopathology : No Microscopic Abnormality Observed : LUNGS, SKELETAL MUSCLE, SPLEEN, AORTA, BRAIN, SPINAL CORD, STOMACH, DUODENUM, JEJUNUM, ILEUM, CECUM, COLON, RECTUM, MESENTERIC LYMPH NODE, SALIVARY GLANDS, MANDIBULAR LYMPH NODE, THYMUS, ADRENAL GLANDS, SCIATIC NERVE, PITUITARY GLAND, PARATHYROID GLANDS, TRACHEA, PHARYNX/LARYNX, EYE(S) WITH OPTIC NERVE, SKIN, PROSTATE, SEMINAL VESICLES, URINARY BLADDER, TESTES, EPIDIDYMIDES, FEMUR/KNEE JOINT, STERNUM, BONE MARROW 643260 . "Terminal Sacrifice Killed on Day : 91 Exposure Group : 90-DAY EXPOSURE Animal is signed off from necropsy Gross Pathology : No Macroscopic Abnormality Observed : LIVER, KIDNEYS, LUNGS, HEART, SKELETAL MUSCLE, SPLEEN, AORTA, BRAIN, SPINAL CORD, STOMACH, DUODENUM, JEJUNUM, ILEUM, PANCREAS, CECUM, COLON, RECTUM, MESENTERIC LYMPH NODE, SALIVARY GLANDS, MANDIBULAR LYMPH NODE, THYMUS, ADRENAL GLANDS, SCIATIC NERVE, PITUITARY GLAND, THYROID GLAND, PARATHYROID GLANDS, TRACHEA, ESOPHAGUS, PHARYNX/LARYNX, EYE(S) WITH OPTIC NERVE, SKIN, PROSTATE, SEMINAL VESICLES, URINARY BLADDER, TESTES, EPIDIDYMIDES, FEMUR/KNEE JOINT, STERNUM, NOSE, MANDIBLE 643260 Continued on the next page .... 957 Company Sanitized. Doe. not contain H-24516: Subchronic Toxicity 90-Day Gavage Study in Rats with One-Generation Reproduction Evaluations INDIVIDUAL ANIMAL GROSS AND MICROSCOPIC OBSERVATIONS Dose Group : VII - Animal Ref 250 mg/kg/day Sex: Males Microscopic & Macroscopic Findings 643260 Continued from previous page Histopathology : LIVER : INFLAMMATION, SUBACUTE/CHRONIC, minimal. HYPERTROPHY, HEPATOCYTE, CENTRILOBULAR, mild. NECROSIS, FOCAL, minimal. KIDNEYS : HYPERTROPHY, TUBULAR, minimal. LUNGS : INFLAMMATION, SUBACUTE/CHRONIC, minimal. THYROID GLAND : ALTERATION, COLLOID, severe. - "HYPERTROPHY, FOLLICULAR, mild. NOSE : DEGENERATION, AMELOBLASTS, mild. MANDIBLE : DEGENERATION, AMELOBLASTS, mild. No Microscopic Abnormality Observed : HEART, SKELETAL MUSCLE, SPLEEN, AORTA, BRAIN, SPINAL CORD, STOMACH, DUODENUM, JEJUNUM, ILEUM, PANCREAS, CECUM, COLON, RECTUM, MESENTERIC LYMPH NODE, SALIVARY GLANDS, MANDIBULAR LYMPH NODE, THYMUS, ADRENAL GLANDS, SCIATIC NERVE, PITUITARY GLAND, PARATHYROID GLANDS, TRACHEA, ESOPHAGUS, PHARYNX/LARYNX, EYE(S) WITH OPTIC NERVE, SKIN, PROSTATE, SEMINAL VESICLES, URINARY BLADDER, TESTES, EPIDIDYMIDES, FEMUR/KNEE JOINT, STERNUM, BONE MARROW 958. Company Sanitized. Does ^ H-24516: Subchronic Toxicity 90-Day Gavage Study in Rats with One-Generation Reproduction Evaluations INDIVIDUAL ANIMAL GROSS AND MICROSCOPIC OBSERVATIONS Dose Group : VII - 250 mg/kg/day Sex: Males Animal Ref Microscopic & Macroscopic Findings 643266 Terminal Sacrifice Killed on Day : 125 Exposure Group : ONE-MONTH RECOVERY Animal is signed off from necropsy Gross Pathology : No Macroscopic Abnormality Observed : LIVER, KIDNEYS, LUNGS, HEART, SKELETAL MUSCLE, SPLEEN, AORTA, BRAIN, SPINAL CORD, STOMACH, DUODENUM, JEJUNUM. ILEUM, PANCREAS, CECUM, COLON, RECTUM, MESENTERIC LYMPH NODE, SALIVARY GLANDS, MANDIBULAR LYMPH NODE, THYMUS, ADRENAL GLANDS, SCIATIC NERVE, PITUITARY GLAND, -THYROID GLAND, PARATHYROID GLANDS, TRACHEA, ESOPHAGUS, PHARYNX/LARYNX, EYE(S) WITH OPTIC NERVE, SKIN, PROSTATE, SEMINAL VESICLES, URINARY BLADDER, TESTES, EPIDIDYMIDES, FEMUR/KNEE JOINT, STERNUM, NOSE, MANDIBLE Histopathology : LIVER : HYPERTROPHY, KIDNEYS : NEPHROPATHY, HYPERTROPHY, THYROID GLAND : ALTERATION, HEPATOCYTE, CENTRILOBULAR, minimal. CHRONIC PROGRESSIVE, minimal. TUBULAR, minimal. COLLOID, minimal. No Microscopic Abnormality Observed : NOSE, MANDIBLE 959 ^ n H-24516: Subchronic Toxicity 90-Day Gavage Study in Rats with One-Generation Reproduction Evaluations INDIVIDUAL ANIMAL GROSS AND MICROSCOPIC OBSERVATIONS Dose Group : VII - 250 mg/kg/day Sex: Males Animal Ref Microscopic & Macroscopic Findings 643283 Terminal Sacrifice Killed on Day : 181 Exposure Group : THREE-MONTH RECOVERY Animal is signed off from necropsy Gross Pathology : No Macroscopic Abnormality Observed : LIVER, KIDNEYS, LUNGS, HEART, SKELETAL MUSCLE, SPLEEN, AORTA, BRAIN, SPINAL CORD, STOMACH, DUODENUM, JEJUNUM, ILEUM, PANCREAS, CECUM, COLON, RECTUM, MESENTERIC LYMPH NODE, SALIVARY GLANDS, MANDIBULAR LYMPH NODE, THYMUS, ADRENAL GLAMDS, SCIATIC NERVE, PITUITARY GLAND, THYROID GLAMD, PARATHYROID GLANDS, TRACHEA, ESOPHAGUS, - "PHARYNX/LARYNX, EYE(S) WITH OPTIC NERVE, SKIN, PROSTATE, SEMINAL VESICLES, URINARY BLADDER, TESTES, EPIDIDYMIDES, FEMUR/KNEE JOINT, STERNUM, NOSE, MANDIBLE Histopathology : LIVER : INFLAMMATION, SUBACUTE/CHRONIC, NECROSIS, FOCAL, mild. KIDNEYS : minimal. NEPHROPATHY, CHRONIC PROGRESSIVE, minimal. THYROID GLAND : ALTERATION, COLLOID, minimal. NOSE : INFLAMMATION, SUBACUTE/CHRONIC, minimal. HYPERPLASIA/HYPERTROPHY, TRANSITIONAL CELL, minimal. EPITHELIUM, 960 c^ww".""-.'""  H-24516: Subchronic Toxicity 90-Day Gavage Study in Rats with One-Generation Reproduction Evaluations INDIVIDUAL ANIMAL GROSS AND MICROSCOPIC OBSERVATIONS Dose Group : VII - Animal Ref 250 mg/kg/day Sex: Males Microscopic & Macroscopic Findings 643295 . Terminal Sacrifice Killed on Day : 181 Exposure Group : THREE-MONTH RECOVERY Animal is signed off from necropsy Gross Pathology : No Macroscopic Abnormality Observed : LIVER, KIDNEYS, LUNGS, HEART, SKELETAL MUSCLE, SPLEEN, AORTA, BRAIN, SPINAL CORD, STOMACH, DUODENUM, JEJUNUM, ILEUM, PANCREAS, CECUM, COLON, RECTUM, MESENTERIC LYMPH NODE, SALIVARY GLANDS, MANDIBULAR LYMPH NODE, THYMUS, ADRENAL GLANDS, SCIATIC NERVE, PITUITARY GLAND, THYROID GLAND, PARATHYROID GLANDS, TRACHEA, ESOPHAGUS, " "PHARYNX/LARYNX, EYE(S) WITH OPTIC NERVE, SKIN, PROSTATE, SEMINAL VESICLES, URINARY BLADDER, TESTES, EPIDIDYMIDES, FEMUR/KNEE JOINT, STERNUM, NOSE, MANDIBLE Histopathology : LIVER : INFLAMMATION, SUBACUTE/CHRONIC, minimal. KIDNEYS : NEPHROPATHY, CHRONIC PROGRESSIVE, minimal. THYROID GLAND : ALTERATION, COLLOID, severe. NOSE : INFLAMMATION, SUBACUTE/CHRONIC, mild. DEGENERATION/NECROSIS, RESPIRATORY, EPITHELIUM, DEGENERATION, AMELOBLASTS, minimal. mild. 961 Company Sanitized. Doe* not c i H-24516: Subchronic Toxicity 90-Day Gavage Study in Rats with One-Generation Reproduction Evaluations INDIVIDUAL ANIMAL GROSS AND MICROSCOPIC OBSERVATIONS Dose Group : VII - Animal Ref 643296 250 mg/kg/day Sex: Males Microscopic & Macroscopic Findings Terminal Sacrifice Killed on Day : 125 Exposure Group : ONE-MONTH RECOVERY Animal is signed off from necropsy Gross Pathology : No Macroscopic Abnormality Observed : LIVER, KIDNEYS, LUNGS, HEART, SKELETAL MUSCLE, SPLEEN, AORTA, BRAIN, SPINAL CORD, STOMACH, DUODENUM, JEJUNUM, ILEUM, PANCREAS, CECUM, COLON, RECTUM, MESENTERIC LYMPH NODE, SALIVARY GLANDS, MANDIBULAR LYMPH NODE, THYMUS, ADRENAL GLANDS. SCIATIC NERVE, PITUITARY GLAND, THYROID GLAND, PARATHYROID GLANDS, TRACHEA, ESOPHAGUS, 'PHARYNX/LARYNX, EYE(S) WITH OPTIC NERVE, SKIN, PROSTATE, SEMINAL VESICLES, URINARY BLADDER, TESTES, EPIDIDYMIDES, FEMUR/KNEE JOINT, STERNUM, NOSE, MANDIBLE Histopathology : LIVER : INFLAMMATION, SUBACUTE/CHRONIC, minimal. HYPERTROPHY, HEPATOCYTE, CENTRILOBULAR, mild. THYROID GLAND : ALTERATION, COLLOID, moderate. NOSE : DEGENERATION, AMELOBLASTS, minimal. No Microscopic Abnormality Observed : KIDNEYS, MANDIBLE 962 Company Sanitized. Does n H-24516; Subchronic Toxicity 90-Day Gavage Study in Rats with One-Generation Reproduction Evaluations INDIVIDUAL ANIMAL GROSS AND MICROSCOPIC OBSERVATIONS Dose Group : VII - 250 mg/kg/day Sex: Males Animal Ref Microscopic & Macroscopic Findings 643298 Terminal Sacrifice Killed on Day : 91 Exposure Group : 90-DAY EXPOSURE Animal is signed off from necropsy . Gross Pathology : No Macroscopic Abnormality Observed : LIVER, KIDNEYS, LUNGS, HEART, SKELETAL MUSCLE, SPLEEN, AORTA, BRAIN, SPINAL CORD, STOMACH, DUODENUM, JEJUNUM, ILEUM, PANCREAS, CECUM, COLON, RECTUM, MESENTERIC LYMPH NODE, SALIVARY GLANDS, MANDIBULAR LYMPH NODE, THYMUS, ADRENAL GLANDS, SCIATIC NERVE, PITUITARY GLAND, THYROID GLAND, PARATHYROID GLANDS, TRACHEA, ESOPHAGUS. - "PHARYNX/LARYNX, EYE(S) WITH OPTIC NERVE, SKIN, PROSTATE, SEMINAL VESICLES, URINARY BLADDER, TESTES, EPIDIDYMIDES, FEMUR/KNEE JOINT, STERNUM, NOSE, MANDIBLE Histopathology : 643298 LIVER : INFLAMMATION, SUBACUTE/CHRONIC, minimal. HYPERTROPHY, HEPATOCYTE, CENTRILOBULAR, mild. KIDNEYS : NEPHROPATHY, HYPERTROPHY, THYROID GLAND : CHRONIC PROGRESSIVE; TUBULAR, mild. minimal. ALTERATION, COLLOID, mild. HYPERTROPHY, FOLLICULAR, mild. NOSE : DEGENERATION, AMELOBLASTS, mild. MANDIBLE : DEGENERATION, AMELOBLASTS, mild. Continued on the next page .... 963  H-24516: Subchronic Toxicity 90-Day Gavage Study in Rats with One-Generation Reproduction Evaluations INDIVIDUAL ANIMAL GROSS AND MICROSCOPIC OBSERVATIONS Dose Group : VII - 250 mg/kg/day Sex: Males Animal Ref Microscopic & Macroscopic Findings 643298 Continued from previous page Histopathology : No Microscopic Abnormality Observed : LUNGS, HEART, SKELETAL MUSCLE, SPLEEN, AORTA, BRAIN, SPINAL CORD, STOMACH, DUODENUM, JEJUNUM, ILEUM, PANCREAS, CECUM, COLON, RECTUM, MESENTERIC LYMPH NODE, SALIVARY GLANDS, MANDIBULAR LYMPH NODE, THYMUS, ADRENAL GLANDS, SCIATIC NERVE, PITUITARY GLAND, PARATHYROID GLANDS, TRACHEA, ESOPHAGUS, PHARYNX/LARYNX, EYE(S) WITH OPTIC NERVE, SKIN, PROSTATE, SEMINAL VESICLES, URINARY BLADDER, TESTES, EPIDIDYMIDES, FEMUR/KNEE JOINT, STERNUM, BONE MARROW 643309 'Accidentally Killed Duration of dosing-days: 70 Exposure Group : REPRODUCTION Animal is signed off from necropsy Gross Pathology : LIVER : DISCOLORATION, SMALL INTESTINE : DISTENDED WITH SALIVARY GLANDS : MOTTLED, TAN. GAS, moderate. EDEMA. SKIN : STAIN, RED. FACE. PLEURAL CAVITY : FLUID, CLEAR, severe. 643309 Continued on the next page .... 964 Company SanBlzed. Does not cont Ah, H-24516: Subchronic Toxicity 90-Day Gavage Study in Rats with One-Generation Reproduction Evaluations INDIVIDUAL ANIMAL GROSS AND MICROSCOPIC OBSERVATIONS Dose Group : VII - 250 mg/kg/day Sex: Males Animal Ref Microscopic & Macroscopic Findings 643309 Continued from previous page Gross Pathology : No Macroscopic Abnormality Observed : KIDNEYS, LUNGS, HEART, SKELETAL MUSCLE, SPLEEN, AORTA, BRAIN, SPINAL CORD, STOMACH, DUODENUM, JEJUNUM, ILEUM, PANCREAS, CECUM, COLON, RECTUM, MESENTERIC LYMPH NODE, MANDIBULAR LYMPH NODE, THYMUS, ADRENAL GLANDS, SCIATIC NERVE, PITUITARY GLAND, THYROID GLAND, PARATHYROID GLANDS, TRACHEA, ESOPHAGUS, PHARYNX/LARYNX, EYE(S) WITH OPTIC NERVE, PROSTATE, SEMINAL VESICLES, URINARY BLADDER, TESTES, EPIDIDYMIDES, FEMUR/KNEE JOINT, STERNUM, NOSE Histopathology : 643309 LIVER : HYPERTROPHY, HEPATOCYTE, CENTRILOBULAR, FATTY CHANGE, CENTRILOBULAR, minimal. NECROSIS, FOCAL, mild. KIDNEYS : minimal. NEPHROPATHY, HYPERTROPHY, LUNGS : CHRONIC PROGRESSIVE, TUBULAR, mild. minimal. INFLAMMATION, SUBACUTE/CHRONIC, minimal. THYMUS : ATROPHY, mild. THYROID GLAND : ALTERATION, COLLOID, moderate. HYPERTROPHY, FOLLICULAR, minimal. PARATHYROID GLANDS : NOT PRESENT. Continued on the next page .... 965 ^^.^ H-24516: Subchronic Toxicity 90-Day Gavage Study in Rats with One-Generation Reproduction Evaluations INDIVIDUAL ANIMAL GROSS AND MICROSCOPIC OBSERVATIONS Dose Group Animal Ref 643309 : VII - . 250 mg/kg/day Sex: Males Microscopic & Macroscopic Findings Continued from previous page Histopathology : ESOPHAGUS : INFLAMMATION, EDEMA, mild. PHARYMX/LARYNX : SUBACUTE/CHRONIC, mild. HEMORRHAGE, mild. EYE(S) WITH OPTIC NERVE : OPTIC NERVE NOT PRESENT. BONE MARROW : HYPERPLASIA, GRANULOCYTIC, mild. NOSE : " "DEGENERATION, AMELOBLASTS, mild. INFLAMMATION, SUBACUTE/CHRONIC, mild. HYPERPLASIA/HYPERTROPHY, TRANSITIONAL mild. MANDIBLE : NOT PRESENT. CELL, EPITHELIUM, No Microscopic Abnormality Observed : HEART, SKELETAL MUSCLE, SPLEEN, AORTA, BRAIN, SPINAL CORD, STOMACH, DUODENUM, JEJUNUM, ILEUM, PANCREAS. CECUM, COLON, RECTUM, MESENTERIC LYMPH NODE, SALIVARY GLANDS, MANDIBULAR LYMPH NODE, ADRENAL GLANDS, SCIATIC NERVE, PITUITARY GLAND, TRACHEA, SKIN, PROSTATE, SEMINAL VESICLES, URINARY BLADDER, TESTES, EPIDIDYMIDES, FEMUR/KNEE JOINT, STERNUM 966 Company SanHIzed. DW no! cont ^, n ^ _ H-24516: Subchronic Toxicity 90-Day Gavage Study in Rats with One-Generation Reproduction Evaluations ^^ INDIVIDUAL ANIMAL GROSS AND MICROSCOPIC OBSERVATIONS Dose Group : VII - 250 .nig/kg/day Sex: Males Animal Ref Microscopic & Macroscopic Findings 643315 Terminal Sacrifice Killed on Day : 91 Exposure Group : 90-DAY EXPOSURE Animal is signed off from necropsy Gross Pathology ; No Macroscopic Abnormality Observed : LIVER, KIDNEYS, LUNGS. HEART, SKELETAL MUSCLE, SPLEEN, AORTA, BRAIN, SPINAL CORD, STOMACH, DUODENUM, JEJUNUM, ILEUM, PANCREAS, CECUM, COLON, RECTUM, MESENTERIC LYMPH NODE, SALIVARY GLANDS, MAMDIBULAR LYMPH NODE, THYMUS, ADRENAL GLAMDS. SCIATIC NERVE, PITUITARY GLAND, THYROID GLAND, PARATHYROID GLANDS, TRACHEA, ESOPHAGUS, " PHARYNX/LARYNX, EYE(S) WITH OPTIC NERVE, SKIN, PROSTATE, SEMINAL VESICLES, URINARY BLADDER, TESTES, EPIDIDYMIDES, FEMUR/KNEE JOINT, STERNUM, NOSE, MANDIBLE Histopathology : 643315 LIVER : INFLAMMATION, SUBACUTE/CHRONIC, minimal. HYPERTROPHY, HEPATOCYTE, CENTRILOBULAR, minimal. KIDNEYS : HYPERTROPHY, TUBULAR, mild. HEART : CARDIOMYOPATHY, minimal. THYROID GLAND : ALTERATION, COLLOID, mild. HYPERTROPHY, FOLLICULAR, mild. PROSTATE : INFLAMMATION, SUBACUTE/CHRONIC, moderate. Continued on the next page .... 967 I con  H-24516: Subchronic Toxicity 90-Day Gavage Study in Rats with One-Generation Reproduction Evaluations___ INDIVIDUAL ANIMAL GROSS AND MICROSCOPIC OBSERVATIONS Dose Group : VII - 250 .nig/kg/day Sex: Males Animal Ref Microscopic & Macroscopic Findings 643315 . Continued from previous page Histopathology : NOSE : DEGENERATION, AMELOBLASTS, mild. HYPERPLASIA/HYPERTROPHY, TRANSITIONAL minimal. MANDIBLE : DEGENERATION, AMELOBLASTS, minimal. CELL, EPITHELIUM, No Microscopic Abnormality Observed : LUNGS, SKELETAL MUSCLE, SPLEEN, AORTA, BRAIN, SPINAL CORD, STOMACH, DUODENUM, JEJUNUM, ILEUM, PANCREAS, CECUM, COLON, -RECTUM, MESENTERIC LYMPH NODE, SALIVARY GLANDS, MANDIBULAR LYMPH NODE, THYMUS, ADRENAL GLANDS, SCIATIC NERVE, PITUITARY GLAND, PARATHYROID GLANDS, TRACHEA, ESOPHAGUS, PHARYNX/LARYNX, EYE(S) WITH OPTIC NERVE, SKIN, SEMINAL VESICLES, URINARY BLADDER, TESTES, EPIDIDYMIDES, FEMUR/KNEE JOINT, STERNUM, BONE MARROW 643316 Terminal Sacrifice Killed on Day : 125 Exposure Group : ONE-MONTH RECOVERY Animal is signed off from necropsy Gross Pathology : 643316 No Macroscopic Abnormality Observed : LIVER, KIDNEYS, LUNGS, HEART, SKELETAL MUSCLE, SPLEEN, AORTA, BRAIN, SPINAL CORD, STOMACH, DUODENUM, JEJUNUM, ILEUM, PANCREAS, CECUM, COLON, RECTUM, MESENTERIC LYMPH NODE, SALIVARY GLANDS, MANDIBULAR LYMPH NODE, THYMUS, ADRENAL GLANDS, SCIATIC NERVE, PITUITARY GLAND, Continued on the next page .... 968 Company Sanitized. Does H-24516: Subchronic Toxicity 90-Day Gavage Study in Rats with One-Generation Reproduction Evaluations INDIVIDUAL. ANIMAL GROSS AND MICROSCOPIC OBSERVATIONS Dose Group : VII - 250 .mg/kg/day Sex: Males Animal Ref Microscopic & Macroscopic Findings 643316 Continued from previous page Gross Pathology : No Macroscopic Abnormality Observed : THYROID GLAND, PARATHYROID GLANDS, TRACHEA, ESOPHAGUS, PHARYNX/LARYNX, EYE(S) WITH OPTIC NERVE, SKIN, PROSTATE, SEMINAL VESICLES, URINARY BLADDER, TESTES, EPIDIDYMIDES, FEMUR/KNEE JOINT, STERNUM, NOSE, MANDIBLE Histopathology : LIVER : INFLAMMATION, SUBACUTE/CHRONIC, minimal. .HYPERTROPHY, HEPATOCYTE. CENTRILOBULAR, mild. FATTY CHANGE, MEDIAN CLEFT, minimal. NECROSIS, FOCAL, minimal. KIDNEYS : NEPHROPATHY, CHRONIC PROGRESSIVE, minimal. THYROID GLAND : ALTERATION, COLLOID, severe. NOSE : DEGENERATION, AMELOBLASTS, mild. No Microscopic Abnormality Observed : MANDIBLE 969 Company Sanitized. Do