Document B550L8JZVX3ZkoML51gRYeLbo

AR226-2824 ^^c>"^/^^ International Research and Development Corporation SPONSOR: E.I. duPont de Nemours and Company SUBJECT: Ninety-Day Feeding Study in the Rat.- Francix X. Wazeter, Director of Research International Researcri^and Development Corporation Collaborators; R. H. Buller, Ph.D., Director of Pharmacology R. G. Geil, D.V.M., Director of Pathology Date: November 30. 1965 poffipany Sanitized. Does not contain TSCA CBB International Research and Development Corporation Page 1 I. SYNOPSIS In a 90-day feeding study, male and female albino rats were fed diets containing flIIHBat levels of 100, 500 or 2500 ppm. After 35 days of continuous'feeding, the 500 and 2500 ppm. dietary levels were increased to 1000 and 5000 ppm., respectively for the remainder of the study. After the prescribed 90-day period of com pound administration, representative animals were placed on a with drawal study. All rats appeared essentially normal with respect to behavior and appearance throughout the study. No adverse effect on body weight gain was found at any dietary level employed in this study, both in the active compound administra tion phase and in the withdrawal period. Average total weekly food consumption measured in grams/rat/week in those groups fed 100 and 500 - 1000 ppm. ofj|^^^^^^in the diet compared favorably with the control rats throughout the study. At the 2500 - 5000 ppm. dietary level, food consumption of the male ra(:s ranged from 1.1 to 8.7 per cent less than control male rats, and food consumption of the female rats ranged from 5.2 to 16.4 per cent less than the female control rats. These differences were first noted in the 8th week for males and in the 4th week for females and continued throughout the treatment period. No meaningful differences in food consumption were reflected by the treated groups of rats in comparison to the control group on the basis pf grams of food consumed per day per kilogram of body weight. No compound-related hematologic or biochemical changes were found ,) Company Sanitized. Does not contain TSCA CB? International Research and Development Corporation Page 2 at the 100 and 500 - 1000 ppm. dietary levels of |B^H9 However, slightly decreased values for erythrocyte counts, hematocrits and hemoglobin concentrations were found for males and females at the 2500 - 5000 ppm. level, particularly at the terminal (90-day) clinicopathology examination. Urinalyses were normal at all times. Compound-related changes observed at the 90-day necropsy examina tion consisted of increased liver and kidney weight at the 1000 and 5000 ppm. dosage levels and pale yellowish livers in some male rats from the 500 - 1000 and 2500 - 5000 ppm. dosage levels. In histologic section, only livers from the 2500 - 5000 ppm. dosage level showed any change and this consisted of a slight hypertrophy of centrolobular hepatocytes. The increase in l^ver and kidney weights and centro lobular hepatocyte hypertrophy persisted with diminished magnitude through 21 days of compound withdrawal. Similar organ weight and histologic changes were observed at the 30 and 60-day interim sacri fices. Company Sanitized. Does not contain TSCA CBt International Research and Development Corporation Page 3 II. COMPOUND The test compound was received from E. I. duPont de Nemours and Company, Wilmington, Delaware, on June 19, 1965. It was a brown amorphous solid in containers bearing the labe] Haskell No. 4212." company Sanitized. Does no? sontain TSCA CB' Inter'national Research and Development Corporation r""~-------------------------------------------------------------- Page 4 III. CLINICAL STUDIES: A. METHODS: 1. General Procedure: Eighty male (weighing from 45 (weighing from 47 to 53 grams) albino were used for this study. to 64 grams) and eighty female rats of the Charles River strain The rats were housed individually in cages suspended above the droppings in an air-conditioned room throughout the study and were fed a diet of Purina Laboratory Chow for rats ad libitum. Water also was available at all times. The animals were divided into one control group and three treated groups of 20 male and 20 female rats each. The rats in each sex group were selected so that the average body weight of each group was similar to that of the other groups of the same sex. 2. Compound Administration: ^^^^U^as incorporated into the standard powdered laboratory diet of Purina Laboratory Chow and offered to the treated groups of rats ad libitum. The test diet was freshly prepared each week and the compound-in-diet levels mixed so that the rats receivedfff^^f at dietary levels of 100, 500, or 2500 ppm. In the sixth week of com pound administration those groups receiving 500 or 2500 ppm. were increased in concentration to dietary levels of 1000 or 5000 ppm., respectively. Those animals receiving 100 ppm. cf^^Hl^^in the diet continued to receive this level throughout the 13-week study period. The control groups of rats received the powdered diet of Purina Laboratory Chow, but without J^^HIy i",orripany Sanitized. Does not contain TSCA CBg buer national Research arid Development Corporation Page 5 Following 13 weeks of compound administration rats in all groups were sacrificed and subjected to necropsy examination with the exception'of certain selected animals from the control'group and from the treated groups at the 1000 and 5000 ppm. dietary levels which were continued on study in a compound withdrawal phase. The withdrawal phase of this study will'be .reported in its entirety in a subsequent and separate report. 3. Observations: The control and test animals were observed daily for mortality, alteration in general appearance and behavior, and signs of pharmacodynamic and/or toxic effects. Body weights, food consumption, and food efficiency values were recorded for each rat weekly throughout the study. 4. Laboratory Tests: a. Hematology: 2 3 Hematologic examination consisted of erythrocyte counts, 1 total and differential leucocyte counts, hematocrits , and hemoglobin concentrations. These studies were performed individually on 6 male and 6 female rats randomly selected in the control and each test group during the control period and again at 30, 60, and 90 days. same b. Urjnalysis: Urine samples were obtained time intervals used to obtain blood from the same animals at the for hematology. Urinalysis Coulter Particle Size Counter, Model A., Coulter Electronics, 590 W. 20th Street, Hialeah, Florida. 2 Miller, S., Microcapillary Method, Textbook of Clinical Pathology, 1960, Williams and Wilkins Company, Philadelphia, Pa., p. 43. 3 Miller, S., Cyanmethemoglobin Method, Textbook of Clinical Pathology, 1960, Williams and Wilkins Company, Philadelphia, Pa., p. 35. C; --';any Sanitized!. DoesnoS contain TSCA C^f International Research and Development Corporation Page 6 consisted of qualitative tests for glucose, * ' blood, ' * and albumin, ' * ' measurements specific gravity, and microscopic examination of bilirubin , occult of volume, pH and the urinary sediments c. Biochemistry; Biochemical examinations were conducted at the same inter vals as for hematology. Serum trahsaininase (SGOT and SGPT) ; .and". plasma alkaline phosphatase determinations were performed on 6 male "Combistix" 5 "Ciinistix" 6 "Clinitest" (Ames Reagent Strips). (Ames Reagent Strips). (Ames Reagent Tablets). "Ictotest" 0 "Hemastix" Q "Hematest" (Ames Reagent Tablets).. (Ames Reagent Strips). (Ames Reagent Tablets). "Occultest" (Ames Reagent Tablets). "Albustix" (Ames Reagent Strips). 17 ~ "Bumintest" (Ames Reagent Tablets). 13 Heller's Ring Test, Practical Physiologic Chemistry, Hawk, Oser and Summerson, 13th Ed., p. 830. Beckman Expanded Scale pH Meter, Model No. 76. Reitman, S., and Frankel, S., Colorimetric Method for the Determina tion of Serum Transaminase Activity, Am. J. of Clin. Path., 28: 56, 1957. 16 Marsh, W., Modified King-Armstrong Method, Clin. Chem. ^: 119, 1959. (i25"oi'n ^pany Sanitized. Dees not contain TSCA CBI International Research and Development Corporation Page 7 and 6 female rats randomly selected from the control and treated groups. The animals chosen for hematology values were not used for these bio chemical determinations. B. RESULTS: 1. General Behavior and Appearance; No adverse changes in behavior or appearance were encountered that could be related to the administration ffffffl Animals in the control and all treated groups appeared essen tially normal each day with the exception of an occasional rat in each group that exhibited slight nasal and/or ocular porphyrin discharge. Other incidental findings, unrelated to compound administration, included one treated female animal (Rat #14374) at the 5000 ppm. dietary level which exhibited a swollen nose in the 13th week of study, one treated male (Rat #14298) at this dietary level which exhibited a mass on the flank from the 16th week (withdrawal period) until terminal necropsy examination, and one treated male (Rat #14324) at this same dietary level which exhibited destruction of the right eye, from the 15th week to the terminal (in the withdrawal period) necropsy examina tion. 2. Body Weights (Tables 1-8 and Figures 1 and 2): a. Control; The control animals maintained body weight curves which were consistent with those curves exhibited by control animals of the same age and strain maintained in these laboratories from time-to-time. b. 100 and 500 ppm.*: Male and female rats at these dietary levels maintained body weights which paralleled closely those of their respective control groups. * 500 ppm. dietary level increased to 1000 ppm. in the 6th week of study. ;:pany Sanitized. Goes no?: contain TSCA CB'I International Research and Development Corporation Page 8 c. 2500 ppm.**: No marked body weight changes occurred among male and female rats at this dietary level during the course of compound administration. Male animals in the 9th week exhibited a body weight gain 8.8 per'cent less than control males. This difference in body weight gain persisted for the duration of the study period. During the withdrawal phase of this study the greatest decrease in body weight gain occurred. Even then, however, this difference was only about.10 per cent less than that of the male control animals. Female treated animals in this group in the 7th week of study exhibited a weight gai-n which was 11.5 per cent less than that of the control female animals. This difference in body weight gain per sisted for the duration of the treatment period. The greatest differ ence in body weight gain of the female group was noted in the 12th week of study at which time a difference of only 11.7 per cent occurred. 3. Food Consumption (Tables 10 and 11); a. Grams/Rat/Week: Average total weekly food consumption for male and female rats in those groups receiving 100 ppm. and 500 ppm.* compared favorably with similar measurements obtained from the control group. Treated rats receiving 2500 ppm.** showed food consumption values less than those of control animals beginning in the 4th week for treated females and in the 8th week for treated males. This decrease in food consumption continued throughout the study period and ranged from 1.1 to 8.7 per cent for the males and 5.2 to 16.4 per cent for the females in this group. The decreased food consumption in this * 500 ppm. dietary level increased to 1000 ppm. in the 6th week of study. ** 2500 ppm. dietary level increased to 5000 ppm. in the 6th week of study. Company Sanitized. Does not contain TSCA CBg rV-\ International Research and Development Corporation Page 9 group continued in both sexes for the duration of the treatment period. b. Grams/Kg./Day: No biologically meaningful differences were observed on food consumption in the treated groups of rats when compared with the control group on a basis of grams/kg./day food consumed. 4. Survival (Table 9): Other than for those animals subjected to interim necropsy examination at 30 and 60 days, all control and treated animals survived the course of study with #14160) succumbed in the male (Rat #14212) at the two exceptions. One control female (Rat terminal (13th) week of study and one treated 100 ppm. level of ]^^H^^ succumbed in the llth week of study. 5. Laboratory Tests: a. Hematology: No compound-related hematologic changes were found at the 100 and 500 ppm. dietary levels 4HilH^ At the 2500 ppm. level, group values for both sexes, with respect to erythrocyte count, hema- tocrit and hemoglobin concentration, generally were slightly lower than those for the control animals and rats at the 100 and 500 ppm. dietary levels of ffl^^fff Although some changes in these parameters were seen at the 60-day interval of examination, they were overall more pronounced after 90 days of compound administration. It is of interest that inspection of these values for individual rats in the high dietary level groups failed to reveal marked changes for any given animal, that is, whereby that animal's value would tend to markedly lower the group average, but rather that lower values, with a relatively small spread from individual to individual, were found for most of these rats. Company Sanitized. Does not contain TSCA 3^ International Research and Development Corporation Page 10 Group average values are summarized for male rats in Table 12 and for female rats in Table 13. Individual values for all male and female rats appear in Tables 14 through 17. b. Plasma Biochemistry; No compound-related changes were found at any period of examination with respect to serum alkaline phosphatase activity or serum glutamic pyruvic transaminase (SGPT) or serum glutamic oxalacetic transaminase (SGOT) activities. Values obtained in these studies appear in Tables 18 through 21. c. Urinalysis: Urinalysis examinations failed to reveal changes which were considered to be related to treatment with the test compound. Results of these measurements appear in Tables 22 through 25. Company Sanitized. Does noi contain TSCA C&f I Imemaiional Research and Development Corporation Page 11 IV. PATHOLOGICAL STUDIES A. METHODS: 1. Gross Examination: After 30 and 60 days of compound administration, 3 male and 3 female rats from the control and each treated group were sacri ficed by exsanguination and subjected to necropsy examination. After 90 days of compound administration, 10 male and 10 female rats from the control, 1000, and 5000 ppm. dietary level groups and all surviving rats from the 100 ppm. group were sacrificed by exsanguina tion and subjected to necropsy examination. Three male and 3 female rats from the control, 1000 and 5000 ppm. groups were sacrificed and subjected to necropsy examination after a 21-day compound withdrawal period. (Other rats that remained on withdrawal beyond 21 days will be reported on in a separate report.) At necropsy major organs were weighed and representative tissues from each rat were collected into 10 per cent neutral buffered formalin for subsequent histologic processing. At the 90-day sacrifice, specimens of brain, liver,.kidneys, muscle, fat, spleen, testes and blood were pooled by sex and dietary group, frozen and forwarded to the sponsor. Specimens of liver from the interim and withdrawal sacrifice were also pooled by sex and dietary group, frozen and shipped to the sponsor. Rats which died on study were also subjected to necropsy examination unless this was precluded by advanced autolysis. 2. Microscopic Examination: The following tissues from each of 3 male and 3 female rats from the control and high dosage groups from the 30 and 60-day interim and 21-day withdrawal sacrifices and from each of 10 male and 10 -^ ....-.. -,.- .^,.^--^ Soss cot contain TSiHI.GES International Research and Development Corporation Page 12 female control and high dietary group rats from the 90-day terminal sacrifice were paraffin-embedded, sectioned, stained with hematoxylin and" eosin and examined microscopically: brain spinal cord peripheral nerve eye pituitary thyroid parathyroid adrenal lung heart spleen lymph node thymus bone marrow salivary gland stomach small intestine large intestine pancreas liver kidneys urinary bladder testes or ovaries prostate or uterus skeletal muscle skin bone Sections of liver from 10 male and 10 female rats from the 1000 ppm. level - 90-day sacrifice rats were also processed as above and examined. B. RESULTS: 1. Gross Pathology (Table 26,) and Organ Weights (Tables 27 and _:29): Compound related gross changes observed at necropsy were limited to male rats from the 1000 and 5000 ppm. dietary level groups and consisted of pale, yellowish livers in some but not all male rats from the 5000 ppm. dietary level group and in a few rats from the 1000 ppm. dietary level group. None of the rats dying on study died of compound related causes. Rat #14160 (Control) died of pneumonia. Autolysis precluded diagnostic necropsy of Rat #14212 (100 ppm.). Compound related variations in organ weights were limited to the livers and kidneys of treated rats. At the 90-day sacrifice there was a moderate increase in actual and relative liver weights of the 1000 and 5000 ppm. dietary level rats. This increase was also seen in the 5000 ppm. dietary level rats at the 60-day interim Company Sar.^zed. Does not contest.' TSCA CBii International Research and Development Corporation Page 13 sacrifice and in the 2500 ppm. dietary level rats at the 30-day interim sacrifice. After 21 days of compound withdrawal, a slight increase in*liver weight persisted at the 5000 ppm. dietary level. - hff^^ Mean actual and relative kidney weights were slightly/^in the 1000 and 5000 ppm. dietary level rats at the 90-day sacrifice. Kidney weights were also slightly increased in the 1000 and 5000 ppm. level rats at the 60-day interim sacrifice and 21-day withdrawal sacrifice and in the 500 and 2500 ppm. level at the 30-day interim sacrifice. Although the values from the interim and withdrawal sacrifices represent only 3 rats per sex group, these variations in kidney weights always had a dietary-level relationship. 2. Histopathology (Tables 29 and 30): Compound related histopathologic changes were found only in the livers of rats from the highest (2500-5000 ppm.) dietary level and consisted of slight hypertrophy of centrolobular hepatocytes. Affected liver cells had cytoplasm which was less coarsely granular and more homogeneous than the unaffected cells at the periphery of the liver lobules and in the livers of rats in the control and lower dietary levels. This change, to a slight degree was seen after 30 days at the 2500 ppm. level. After this group was raised to 5000 ppm., the change was more marked at the 60 and 90-day sacrifices. A very slight change persisted in the 5000 ppm. level male rats sacrificed after a 21-day compound withdrawal period. This liver change was always more marked in male rats and was seen only at the highest (2500-5000 ppm.) dietary level. No lesions in other organs were considered to have been of compound related origin. No histologic basis was found for the slight increase in kidney weights in treated rats. T;3n'>? SanSSized. Does not contain TSCACBfi 1 TABLE 1. Rat Number Ninet y-Day Feedirig Study in the Rat. Indiv idual Weeklyi Body Weigl-its, GramS. Contr ol Period 1 2 1 2 3 Control - 14142 14143 14144 14145 14146 14147 14148 14149 14150 14151 14152 14153 14154 14155 14156 14157 14158 14159 14160 14161 Female: 55 54 56 56 56 55 57 60 55 58 56 50 57 57 51 58 57 58 50 54 93 68 99 83 94 91 88 101: 72 83 67 52 63 71 67 64 73 54 76 48 129 95 134 107 136 123 124 135 103 116 114 93 82 116 115 105 106 99 124 91 149 123 163 130 161 141 149 162 126 137 133 122 117 142 139 121 132 146 147 128 175 136 187 142 184 160 170 177 149 158 154 138 141 160 161 134 153 156 162 148 Mean 55 75 112 138 157 Compounc1 Administ ration Weelks 4 5 6 7 185 144 207 159 196 179 178 199 164 181 171 143 156 170 161 154 149 181 157 144 169 195 155 249 166 217 184 197 215 191 189 189 166 172 192 196 153 172 199 189 178 188 Sacrificed 169 191 260 285 Sacrificed Sacrificed 191 231 214 249 230 261 213 243 202 237 203 235 183 231 195 237 203 239 210 243 166 165 190 232 219 240 206 221 192 231 203 234 SaniUzed.DcesnotconU.iTnSCACB8 Company TABLE I. Rat Number Ninety~Day Feeding Study in the Rat. Continued. Individual Weekly Body Weights, Grams. Compound Administration Weeks 11 12 13 14* 15 16 17 18 Control Female: 14144 14147 14148 14150 14151 14153 14154 14155 14156 14157 14158 14159 14160 14161 14313 320 326 332 244 252 332 271 285 267 285 288 233 241 251 242 260 248 244 256 263 241 265 271 238 275 283 259 200 200 191 245 253 231 250 264 266 Sacrificed 277 281 282 289 299 310 Sacrificed 265 271 Died 241 251 257 261 268 276 Sacrificed 242 249 251 256 255 Mean 260 266 258 261 270 276 256 255 * Initiation of withdrawal period (14th week). 19 254 254 "^y5anit1^ ^S/t,'^on, a^ 75c A CB/  TABLE 2. Rat Number Ninety'-Day Feeding Study in t:he Rat. Indivi.dual Weekly B ody Weight:s. Granus. Centre)1 Period 1 2 L 2 3 Control - Male: 14162 64 14163 62 14164 60 14165 59 14166 55 14167 50 14168 61 14169 45 14170 58 14171 51 14172 60 14173 52 14174 51 14175 54 14176 57 14177 54 14178 62 14179 52 14180 53 14181 55 Mean 55 99 97 100 94 92 67 98 74 95 83 83 55 64 76 76 71 64 66 67 67 79 143 151 89 157 133 103 147 113 136 119 152 105 113 137 136 123 117 130 120 128 128 185 207 169 214 175 145 189 143 185 158 205 153 155 185 180 167 153 181 172 177 175 230 256 229 251 211 187 243 224 231 191 263 199 204 234 222 209 200 231 224 234 224 '-------- Compourid Adminis tration We eks 4 5 6 7 244 , 294 288 309 248 231 276 274 265 260 307 242 238 251 264 241 '234 238 272 241 261 263 309 324 346 274 260, 308 307 285 257 300 263 273 293 294 271 250 261 300 300 287 Sacrific ed 338 354 366 388 Sacrificed 300 321 290 311 Sacrificed 337 365 317 348 287 310 336 371 291 306 318 341 3,17 370 328 354 300 318 283 311 322 347 334 360 344 373 318 344 K^any SanW.ed. Does no. contain TSCA C-M TABLE 2. Rat Number Ninety-Day Feeding Study in the Rat. Continued. Individual Weekly Body Weights, Grams. Compound Administration Weeks 11 12 13 14* 15 16 17 18 Control Male; 14163 14164 14166 14169 14171 14172 14173 14174 14175 14176 14177 14179 14180 14181 14314 14315 406 391 375 505 505 495 398 409 383 446 453 431 412 423 385 488 483 478 389 405 376 427 440 401 498 496 506 442 452 425 365 374 357 396 402 414 Sacrificed 435 455 461 479 489 500 Sacrificed 415 463 461 489 472 514 Sacrificed 451 463 472 47.6 466 497 506 515 538 518 556 574 571 512 503 523 539 544 Mean 434 444 429 482 475 501 540 543 * Initiation of withdrawal period (14th week). 19 522 585 559 555 company sanlt'^ Does not contain TSCA CP- h, m TABLE 3. Rat Number Ninet y-Day Feeding Study in the Rat-- Indiv idual Weekl y Body Weighit. Granas. Contr ol Period 1 2 1 2 3 Compounid Administ]ration We eks 4 5 6 7 100 ppm. - Female: 14182 56 14183 51 14184 59 14185 55 14186 57 14187 55 14188 55 14189 55 14190 55 14191 53 14192 54 14193 53 14194 61 1419.5 59 14196 57 14197 50 14198 62 14199 51 14200 53 14201 59 Mean 56 86 77 82 87 101 76 80 63 88 84 60 67 73 69 65 58 76 60 70 65. 74 112 131 151 167 175 Sacrificed 123 153 171 203 210 231 250 2 113 126 145 165 182 194 211 2 110 135 154 174 186 Sacrificed 144 176 210 252 251 275 290 3 109 134 155 175 194,. 206 230 2 111 124 139 149 162 Sacrificed 91 119 150 168 177 198 216 2 116 137 154 176 180 200 211 2 122 153 177 187 208 223 241 2 106 127 141 172 174 185 193 2 113 141 158 181 199 210 222 2 90 124 148 160 179 203 221 2 . 107. 133 157 175 190 211 231 2 105 147 159 179 183 199 213 2 98 121 146 157 179 197 207 2 . 123 141 167 195 202 220 237 2 102 125 141 144 180 197 215 2 123 147 165 184 197 212 224 2 115 152 179 183 208 235 245 112 137 158 177. 191 212 22.7 company Sanitized. Does not contain TSCA CBt mHf9 TABLE 3. Ninety-Day Feeding Study in the Rat. Continued. Individ ual Weekly Body Weights, Grams. Rat Number .,-.- - Compound Administration Weeks 11 12 13 " 14- 15 16 17 100 "ppm..: - 14183 14186 L4187 14189 14190 14191 14192 14195 . 14196 14197 14198 14199 14200 14201 Female: 290 3'45 271 272 248 287 236 280 277 251 283 261 273 298 306 353 285 274 255 303 248 286 276 262 296 269 278 301 283 333 258 252 227 283 221 261 247 244 278 273 285 308 Mean 277 285 268 18 , 19 @mp8iiySanitized. Does not contain TSCA CBI r TABLE 4. Rat Number Niriet;y-Day Feed:Lng Study i n the Rat. Indiv:Ldual Week ly Body Wei.ght. Grams. Contnol Period 1 2 1 2 3 1.00 ppm. - Male: 14202 58 14203 51 14204 62 14205 55 14206 63 14207 54 14208 5.5 14209 55 14210 60 1421.1 54 14212 50 14213 53 14214 61 14215 63 14216 53 14217 49 14218 58 14219 55 14220 61 14221 60 79 76 87 86 103 85 81 88 86 87 60 81 83 83 70 58 64 73 68 74 119 116 149 139 160 124 120 128 142 134 108 116 149 136 126 97 100 121 110 135 168 157 203 189 215 165 159 166 197 173 122 161 205 171 164 135 142 155 136 176 214 201 256 242 255 209 199 209 252 217 130 195 267 210 217 168 199 207 196 227 Mean 57 79 127 168 214 Compo'und AdminJLstration Weieks 4 5 6 7 8 246 : 270' Sacrificed 224 261 , 296 328 35 310 343, 371 407 44 275 286 Sacrificed 298 320 346 373 40 248 282. 306 338 3 211 228 Sacrificed 244 254 269 301 3 303 330 354 388 3 251 284 312 339 3 168 211 250 256 2 238 243 271 290 3 284 326 352 377 3 250 259 267 289 3 271 308 247 377 4 186 219 260 286 3 247 286 330 369 3 216 275 310 333 3 213 264 287 307 3 255 281 308 331 3 252 277 308 335 3 ^ RfggRteA g@@8no( contain TSCA CBI --^ Ninety-Day Feeding Study in the Rat. Continued. Individual Weekly Body Weight, Grams. Compound Administration Weeks 11 12 13 14 15 16 17 18 19 Male: 411 521 450 423 385 462 432 Died 353 446 385 482 473 406 433 440 527 468 436 398 477 456 368 456 405 501 496 421 450 427 515 432 410 363 481 432 348 448 383 500 507 430 437 Qomp, ^ysa^.^ ^^rscAcB,  TABLE. 5. Rat Number Ninety- Day Feedirig Study in the Rat. Individlual Weekly' Body Weig ht. Grams>. Control. Period 1 2 1 2 3 500 ppm. - Female:*' 1.4222 1.4223 14224 14225 1.4226 14227 14228 1-4229 14230 14231 14232 14233 14234 14235 14236 14237 14238 14239 14240 14241 55 88 60 83 58 92 48 59 57 73 57 92 5.5 86 55 78 55 90 52 76 50 57 52 64 59 73 58 68 56 76 52 52 50 77 57 74 55 75 55 72 126 116 111 "91 115 130 130 113 119 114 100 105 110 119 117 86 119 129 117 100 153 134 127 115 140 157 154 140 134 153 134 125 129 148 150 123 150 146 138 128 177 154 141 136 161 178 166 160 147 184 147 130 140 175 171 145 171 163 154 144 Mean 55 75 113 139 157 Compo und Admin istration 1Weeks 4 5 6 7 8 190 172 163 141 182 201 178 174 158 195 174 148 140 201 193 146 195 183 157 143 172 204 181 185 154 188 210, 197 184 175 219 186 160 164 214 213 168 199 198 188 180 188 Sacrificed 195 202 213 200 21.2 238 Sacrificed 204 215 223 230 244 256 Sacrificed 202 215 237 190 202 215 237 254 272 204 216 23 170 181 19 176 187 19 255 249 26 216 236 24 188 200 21 211 222 22 206 221 23 197 214 22 188 200 20 204 216 22 Dosage level increased in the 5th week of study to 1000 ppm. Company Sanitized. Does not contain TSCA CB6 TABLE 5. Rat Number Ninety-Day Feeding Study in the Rat. Continued. Individual Weekly Body Weights, Grams. Compound1 Ad-minis t ration Weel<..S 11 12 13 14* 15 16 17 18 500 PPTO. - Female: 14224 14226 14227 14229 14231 14232 14233 14235 14236 14237 14238 14239 14240 14241 14306 14308 14320 267 279 263 246 257 239 244 282 269 265 277 270 310 314 268 255 269 251 212 216 207 304 312 299 262 272 254 232 244 234 253 256 242 263 276 278 Sacrificed 259 266 261 262 272 279 Sacrificed 256 263 259 274 278 280 Sacrificed 235 245 246 254 269 267 269 282 254 266 270 272 284 249 258 266 265 273 234 236 241 246 250 Mean 257 268 254 256 265 269 263 272 * Initiation of withdrawal period (14th week). 19 ' 276 284 283 253 274 Company Sanitized. Does not contain TSCA CBI NTn efcy-Day Feieding Study in t;he Rat. TAB7JS. 6. Rat Number Ind ividual W(iekly Body Weight:, Grams. Con.trol Peri(3d 1 2 1 2 3 500 ppm. - Male/ 14242 14243 14244 14245 14246 14247 14248 14249 14250 14251 14252 14253 14254 1.4255 14256 14257 14258 14259 14260 14261 58 85 57 92 56 78 63 96 56 63 58 72 55 83 62 90 58 85 52 75 63 89 62 78 55 75 57 70 55 67 53 81 56 98 52 63 58 69 59 79 124 136 134 136 91 120 114 134 130 124 147 144 134 123 102 117 151 105 124 151 155 178 196 172 133 162 149 176 192 1.65 195 189 187 162 140 154 189 145 169 203 185 226 249 213 172 209 183 224 236 207 249 230 235 188 182 192 235 191 220 271 Mean 57 79 127 170 215 Compoumd Admin:istration W eeks 4 5 6 7 8 201 269 295 251 210 266 208 270 276 239 293 238 258 221 221 219 285 225 229 285 248 228 297 314 265 234 305 234 291 300 272 321 299 297 250 258 268 328 249 289 324 281 Sacrificed 325 351 37 371 412 44 Sacrificed 268 292 32 342 365 38 Sacrificed 325 356 38 321 334 35 297 328 35 355 326 39 327 355 37 317 348 38 281 306 32 280 300 32 306 339 36 359 385 41 274 303 3 324 352 3 377 408 4 321 345 3 * Dosage level increased in the 5th week of study to 1000 ppm. .^.o.--------------"' Conwany Si \ ^ y -. :.::.?:::.:!.!1!.:.; TABLE 6. Rat Number Ninety-Day Feeding Study in the Rat. Continued. Individual Weekly Body Weights, Grams. Compound Administration Weeks 11 12 13 14* 15 16 17 18 500 ppm. - Male: 14243 14244 14247 14249 14250 14252 14254 14255 14256 14257 14258 14259 14260 14261 14321 14322 14325 445 435 422 509 525 499 449 471 447 434 451 441 412 431 411 453 463 434 452 437 428 382 396 380 369 377 348 408 415 390 478 499 477 517 496 545 Sacrificed 384 404 419 435 446 465 Sacrificed 400 417 434 452 458 476 Sacrificed 500 520 548 568 542 563 582 612 507 487 532 538 559 516 497 531 545 550 549 525 562 569 586 Mean 434 446 434 506 493 525 559 577 Initiation of withdrawal period (14th week). 19 632 544 549 577 576 'Company Sanitized. Does not contain TSCA CBI Ninety-1ay Feedi ng Study iri the Rat. TABLE 7. Rat lumber Individi.i.al Weekl y Body Wei^;hts, Gram S. Control Period 1 2 1 2 3 * 2500 ppm. - Female 14262 14263 14264 14265 14266 14267 14268 14269 14270 14271 14272 14273 14274 14275 14276 14277 14278 14279 14280 14281 52 87 53 79 53 71 55 72 50 63 55 76 63 85 56 86 56 85 60 95 58 74 51 66 47 61 57 75 52 63 52 66 47 55 61 76 56 75 53 66 120 119 107 104 78 113 114 115 116 134 117 116 99 122 107 106 85 123 126 108 138 145 124 127 109 134 132 130 136 161 134 140 133 144 135 134 115 144 154 132 164 166 140 143 133, 147 137 148 151 180 148 161 151 168 148 152 141 160 178 146 Mean 55 75 113 136 154 C'ompound Administ;ration. We.eks 4 5 6 7 174 182 149 154 153 163 135 163 161 187 158 169 171 174 162 151 149 155 173 142 161 181* 200 160 165 171 175 158 173 171 212 173 185 182 198 179 168 174 185 204 171 179 Sacrificed 230 246 169 180 Sacrificed 181 195 188 202 Sacrificed 182 192 174 184 225 240 186 193 197 202 195 206 207 222 191 209 188 196 189 198 206 211 221 233 180 189 196 207 Dosage level increased in the 5th week of study to 5000 ppm. Company Sanitized. Does not containT5CA_CB|  Ninety-Day Feeiding Stuciy in the ]^at. TABLE 7. Rat Number Continuec1. Ind:Lvidual W(iekly Body Weights, Cirams. Compound t^dministrat:ion Week s 11 12 13 14* 15 16 17 18 2500 pom. - Female: 14264 14266 14267 14269 14271 14272 14273 14274 14276 14277 14278 14279 14280 14281 14311 14326 14329 205 216 201 226 228 213 234 244 213 214 217 208 261 264 244 207 210 204 226 233 223 226 218 212 262 260 263 228 232 212 229 241 231 249 259 270 Sacrificed 236 239 237 257 254 269 Sacrificed 274 276 276 278 284 285 Sacrificed 214 216 218 222 239 245 252 258 233 246 253 260 278 233 236 239 246 258 198 202 209 207 220 Mean 232 235 225 239 246 253 241 254 * Initiation of withdrawal period. (14th week) SHS^^^M ^^^K^^IB^Br Company Sanitized. Does not contain TSCACBI 19 ^ 257 278 261 218 254 '^y Ninety -Day Feedi ng Study iri the Rat TABLE 8. Rat Number Indivi dual Weekl y Body Wei^;hts, Graims. Contro 1 Period 1 2 1 2 3 * 2500 ppm. - Male 14282 14283 14284 14285 14286 14287 14288 14289 14290 14291 14292 14293 14294 14295 14296 14297 14298 14299 14300 14301 60 80 53 84 55 76 55 84 52 65 55 84 46 71 60 98 56 84 57 60 52 69 57 82 58 82 64 92 61 84 58 75 52 82 63 89 55 78 52 76 117 124 129 133 92 133 193 151 125 107 72 143 133 149 144 133 107 143 114 132 141 151 182 178 125 181 171 194 154 163 104 184 165 189 189 196 140 190 135 169 184 193 219 226 147 227 227 249 193 206 138 228 207 228 . 231. 247 178 241 197 205 Mean 56 80 129 165 209 Compound Adminisftration Wee ks 4 5 6 7 225 237 277 260 173 262 265 298 234 228 181 261 231 265 . 272 281 214 290 215 240 245 246 268 310 283 203 289 274 322 275 271 203 285 266 294 295 323 236 325 272 271 276 Sacrificed 299 321 351 382 Sacrific ed 222 245 308 332 Sacrificed 373 404 314 335 306 332 239 273 312 339 291 315 341 378 321 345 363 396 258 284 351 378 303 325 292 312 308 335 * Dosage level increased in the 5th week of study to 5000 ppm. Company Sanitized. Does not contain TSCA C8S ^ Ninety-Day Feeding Study in the Rat. TABLE 8. Rat Number Continued. 11 Individual Weekly Body Weights, Grams. (compound Administr;ition WeetCS 12 13 14* 15 16 17 18 2500 ppm. - Male: 14283 14284 14286 14287 14290 14291 14292 14294 14296 14297 14298 14299 14300 14301 14327 14328 14324 394 410 393 478 507 497 318 328 316 400 414 401 415 425 413 401 410 385 344 373 357 367 388 364 405 418 412 468 480 456 349 465 327 341 339 342 Sacrificed 453 463 476 472 473 512 Sacrificed 381 395 407 416 429 442 Sacrificed 382 398 414 431 447 448 466 486 362 377 390 497 427 492 500 517 537 550 461 478 489 500 516 Mean 397 420 401 425 435 449 500 495 * Initiation of withdrawal period. (14th week) 19 508 433 556 531 507 Company Sanitized. Does not contai'n TSCACB3 500i-- FIGURE 1. Group Mean Body Weights. Female Rats <o Control 450 400 350 - 0 100 ppm. A 500 ppm. - 1000 ppm. 0 2500 ppm. - 5000 ppm. 300 250 200 150 100 50 ^ ^ 0 t> A 6 6 0 0 1 ' 12 3 8 9 10 11 12 13 14 COMPOUND ADMINISTRATION WEEKS .Company Sanitized. Does not contain TSCA CBS K^ FIGURE 2. Group Mean Body Weights. Male Rats, 1-- 0 - > A 0 Control . ioo ,,,,. 500 ppm. - 1000 ppm. 2500 ppm. - 5000 ppm. A. b . 6 ' ^ V ^ A ^ 0 fr 0 A t> Q 0 @ -^ .01-11 UU9 i 2 i 3 i 4 \ 5 f 6 i 7 i 8 COMPOUND i i i 9 10 11 ADMINISTRATION i 12 WEEKS i 13 i 14 ompany Sanitized. Does not contain TSCA CB1 1 Ninety'"Day Feedirig Study iri the Rat. .BLE 9... Mean I iody Weightsi, Grams; \ height Raiiges, Gramss; and Surv ival: F]EMA.LE RATS. imp 01-md Control LOO ppm. 500 ppm.* Imin:i-s- Mean Mean Mean M ati(3n Body \ ^sight Body \ height Body Weight Bo feek;3 Wt. I langes Si-irvival Wt. I ranges Survival Wt. Ranges Survival W 0 55 50-60 20/20 56 51-62 20/20 55 48-60 20/20 0 75 48-101 20/20 74 58-101 20/20 75 52-92 20/20 1 112 82-136 20/20 112 .91-144 20/20 113 86-130 20/20 1 2 138 117-163 20/20 137 119-176 20/20 139 115-157 20/20 1 3 157 L34-187 20/20 158 139-210 20/20 157 130-184 20/20 1 4 169 L43-207 20/20 177 144-252 20/20 172 140-201 20/20 1 5 188 153-249 17/20 191 174-251 17/20 188 154-219 17/20 1 6 203 166-260 17/20 212 185-275 17/20 204 170-237 17/20 1 7 234 165-285 17/20 227 193-290 17/20 216 181-254 17/20 2 8 229 174-296 17/20 242 207-303 17/20 229 191-272 17/20 2 9 236 178-306 14/20 251 215-307 14/20 243 201-287 14/20 2 10 251 135-314 14/20 269 234-331 14/20 255 204-303 14/20 2 11 260 230-320 14/20 277 236-345 14/20 257 212-310 14/20 2 12 266 230-326 14/20 285 248-353 14/20 268 216-314 14/20 2 13 258 191-332 13/20 268 221-333 14/20 254 207-299 14/20 2 14 267 250-289 3/20 15 277 254-299 3/20 16 284 256-310 3/20 0/20 259 249-274 270 258-278 273 266-280 6/22 2 6/22 6/22 17 0/20 269 265-272 3/22 18 280 273-284 3/22 19 281 276-284 3/22 TE - Withdrawal period was initiated following 13-weeks of compourid admini.stration. Selected anim the period of withdrawal which continues at the wr iting of .riiis repolt. *-DOS age lev el in this group increased to 1000 ppm, in the 5th week of a^Compaliy Sanitized. Does Dosage lev el in this group increased to 5000 ppm; in the 5th week of studyi ft ^lir\ nety-Day Feediing Study ini the Rat. LBLE .'. Cont inued. Mean. Biody Weights(, Gra,ms; Weight Reinges , Gram.'s; and Survival: MALE RATS. impound Control 100 ppm. 500 ppm.* Iminis- Mean Mean Mean M ation Body Weight Body Weight Body Weight B (eeks Wt. Ranges Survival Wt. Ranges Survival Wt. Ranges Survival W 0 55 45-64 20/20 57 49-63 20/20 58 52-63 20/20 0 79 55-100 20/20 79 58-103 20/20 80 63-98 20/20 1 128 89-157 20/20 127 97-160 20/20 127 91-151 20/20 1 2 175 143-214 20/20 168 122-215 20/20 169 125-203 20/20 1 3 224 187-263 20/20 214 130-267 20/20 215 172-271 20/20 2 4 261 231-309 20/20 252 168-310 20/20 248 201-293 20/20 2 5 287 250-346 17/20 277 211-343 17/20 281 234-324 17/20 2 6 318 283-366 17/20 308 250-371 17/20 321 268-377 17/20 3 7 344 306-388 17/20 335 256-407 17/20 345 292-412 17/20 3 8 376 308-446 17/20 362 296-448 17/20 373 320-443 17/20 9 397 341-461 14/20 376 317-467 14/20 390 334-465 14/20 10 420 358-480 14/20 409 300-495 14/20 415 351-485 14/20 11 434 365-505 14/20 429 353-521 13/20 434 369-509 14/20 12 444 374.-505 14/20 446 368-527 13/20 446 377-525 14/20 13 429 357-506 14/20 437 363-515 13/20 434 348-548 14/20 14 447 242-538 7/23 0/20 472. 234-568 8/24 15 443 249-518 7/23 461 236-542 1/24 .. 16 465 251-556 7/23 17 469 256-574 4/23 18 471 255-571 4/23 19 480 254-585 4/23 489 241-563 496 246-582 511 250-612 511 253-632 8/24 5/24 5/24 5/24 TE " Withdrawal period was initiated following 13-weeks of compound administration. Selected anim period of withdrawal which continues at the writi):ig of this report. k Dosage level in this group increased to 1000 ppm. in the 5th week of study. ** Dosage level in this group incr eased to 5000 ppm. in the 5th week of study Company Sanitized1. Ooe w N inety-'Day Feeding Stiudy in the: Rat. TABLE 1 0. FEMALE RATS: :. Mea.n Food iConsumpticn, Gra'ms/Rat/'Week and Grams/Ki logram,/Day; Mil.igrams/'Kilograms/'Day an d Food Efficiency. CiDmpound C Compoun d Adminis tration week CO NTROL F OOD g/r/wk g/kg/d Eff. 1'00 ppm. FOOD g/r/wk g/kg/d Eff. CPD. mg/kg/d 500ppm. * FOOD g/r/wk g/kg/d Eff. CPD. mg/kg/d 2 g/r/wk 0 ----.. . 1 96.1 122.3 99.6 126.8 '12.7 .98.9 124.8 62.4 91.4 2 110.5 114.5 0.24 110.7 115.3 0.23 11.5 111.9 115.1 0.23 57.6 107.0 3 110.8 100.6 0.17 116.6 105.7 0.18 10.6 117.9 107.0 0.15 53.5 108.9 4 104.4 88.1 0.11 113.7 91.5 0.17 9.2 108.1 89.5 0.14 44.8 95.4 5 113.8 86.7 0.17 113.1 84.8 0.12 8.5 110.2 83.5 0.15 41.8 107.6 6 105.7 74.4 0.14 110.8 74.5 0.13 7.5 105.5 74.0 0.15 74.0 100.2 7 111.5 67.9 0.28 115.4 72.7 0.13 7.3 110.5 73.1 0.11 73.1 102.7 8 113.2 70.7 -.04 117.7 69.4 0.13 6.9 111.7 69.9 0.12 69.9 103.5 9 108.1 65.3 0.07 112.8 64.1 0.08 6.4 112.2 65.8 0.12 65.8 93.6 10 102.4 58.2 0.15 121.4 64.3 0.15 6.4 123.9 69.4 0.10 55.9 107.8 11 112.6 61.6 0.09 129.4 66.8 0.06 6.7 116.7 65.0 0.02 65.0 98.0 12 116.2 62.4 0.05 124.0 62.1 0.06 6.2 116.8 62.3 0.09 62.3 97.2 13 123.9 68.6 -.05 128.1 68.3 -.13 6.8 128.8 72.4 -.11 72.4 112.0 14 ***58 . 0 54.3 +.09 ***59.7 57.5 +.05 ***66.8 15 110.7 57.0 +.09 113.7 60.0 +.10 118.0 16 114.0 57.4 +.06 17 18 111.0 109.3 111.0 58.2 58.0 56.8 +.03 -.04 +.01 115.2 121.0 119.5 19 110.7 56.2 +.01 111.5 NOTE * ** *** Withdrawal period was initiated following:13-weeks of compound administr;ition. into t he period of withdrawal which continues at the writing''of this report. Dosage level increased to 1000 ppm. in the 5th week of study. Dosage level increased to 5000 ppm. in the 5th week of study. Grams/ rat/4'days. Selected Compaly San^zed. Does nol contain T  TABLE 3LI. llinety-D,ay Feedling Stuidy in thia Rat. MALE ]RATS: IAean Fc>od Cons umption, Grams</Rat/Weel< and Grains/Kilog rams/Dciy; Compc)und Con and Fbc>d Effic iency. Compoul'ld Admini,'3- tratiola week C01^TROL . - FOOD g/r/wk g/kg/d Eff. 1 OO^-ppm. FOOD g/r/wk g/kg/d Eff. CPD. mg/kg/d 5'00 ppm.* F OOD g/r/wk g/kg/d Eff. CPD. mg/kg/d g/r/wk 0 i 108.8 121.1 99.6 118.3 11.8 100.4 112.6 56.3 112.2 2 135.5 110.9 126.3 107.1 0.33 10.7 128.8 108.9 0.33 54.5 121.6 3 150.3 96.0 141.9 94.9 0.32 9.5 144.9 96.3 0.31 48.2 140.5 4 151.7 83.1 151.1 85.7 0.25 8.6 145.3 83.9 0.23 42.0 145.0 5 151.0 75.3 0.11 152.8 78.7 0.20 7.9 154.9 78.6 0.21 39.3 151.9 6 146.6 65.7 0.21 148.0 68.5 0.21 6.9 150.0 66.7 0.26 66.7 149.9 7 155.1 64.5 0.17 157.1 66.9 0.18 6.7 151.6 62.9 0.16 62.9 152.3 8 165.2 62.8 0.19 158.2 62.4 0.17 6.2 161.8 61.9 0.17 61.9 154.1 9 154.1 55.4 0.14 154.1 58.5 0.09 5.9 148.6 54.4 0.11 54.4 140.7 10 159.9 54.3 0.14 166.6 58.2 0.20 5.8 162.5 55.9 0.15 55.9 146.8 11 158.1 52.1 0.09 175.2 58.3 0.11 5.8 164.4 54.1 0.12 54.1 156.4 12 162.8 52.5 0.06 170.9 54.7 0.10 5.5 159.6 51.1 0.08 51.1 150.6 13 184.8 61.5 -.08 186.2 60.9 -.07 6.1 181.3 59.7 -.07 59.7 178.5 14 ickicQQ: 4 45.0 +.13 ***89.3 47.2 +.24 ***79.6 15 145.1 46.7 -.03 150.3 46.6 -.07 138.8 16 159.0 48.8 +.14 169.0 49.3 +.17 138.4 17 162.0 49.3 +.02 167.4 48.2 +.04 138.3 18 149.3 45.2 +.01 145.0 40.5 +.10 143.5 19 149.5 44.6 +.06 161.8 45.2 0 145.5 NOTE - Withdrawal period was initiated following 13-weeks of compound administration. into the period of withdrawal which continues at the writing of this report. * Dosage level increased to 1000 ppm. in the 5th week of study. ** Dosage level increased to 5000 ppm. in the 5th week of study. *** Grams/rat/4 days. Selected company Sanitized. Does not contain TSCA G8? ^^^^^B TABLE 12. Hematology Ninety-Day Feeding Study in the Rat. Summary of Hematologic Values for Male Rats. Compound Adminis tration Month Control 100 ppm. Page 34 500 ppm.* 2500 ppm.*^ Hematocrifc, % - 0 47 45 45 44 1 48 46 47 43 2 48 45 45 38 3 48 47 45 38 Hemoglobin gms./lOO ml. Erythrocytes, xlO /cnm. Leucocytes, xlO^/cmm. Neutrophils, 7o Seg., 7o Non-Seg., 7o Lymphocytes, 7o Monocytes, 7 Eosinophils, 7o Basophils, 7o 0 12.7 12.7 12.3 12.4 1 14.6 14.1 14.5 13.3 2 15.9 15.2 15.3 13.2 3 15.7 15.0 14.7 12.0 0 6.38 6.04 6.21 6.04 1 6.60 6.74 6.43 6.31 2 "7.21 7.55 7.35 6.29 3 7.16 7.05 7.06 5.90 0 10 75 9.90 12.48 11.30 1 11.79 11.21 8.83 8.62 2 11.22 9.40 11.24 11.93 3 15.25 10.28 11.15 11.55 0 15 . 15 15 12 1 7 17 14 11 2 14 - 13 14 11 3 17 20 16 8 0 1 1 0 1 1 0 0 0 0 2 0 0 0 0 3 0 0 0 0 5 0 83 82 83 85 0 < 1 90 82 85 87 0 2 83 84 84 87 w 3 80 78 82 89 C "<5 E 0 1 1 1 1 0 0 1 2 0 1 1 "5 2 3 2 1 1 Cm 3 2 0 1 1 0) 0 Q 0 0 1 1 1 T3 1 1 1 0 1 0) N 2 0 1 1 1 'C 3 1 2 1 2 (0 CO > 0 0 0 0 0 K- 1 0 0 0 0 C 2 0 0 0 0 C C 3 0 0 0 0 Dosage level in this group increased to 1000 ppm. in the 5th week of study. Dosage level in this group increased to 5000 ppm. in the 5th week of study. vl^^^H^ TABLE 13. Hematology Ninety-Day Feeding Study in the Rat. Summary of Hematologic Values for Female Rats. Compound Admini S- tration Month Control 100 ppm. Page 35 500 ppm.* 2500 ppm. ** Hematocrit, 7o Hemoglobin gms./lOO ml. Erythrocytes, xlO^ciiim. Leucocytes, xlO /cmm. Neutrophils, % Seg., 7o Non-Seg., % Lymphocytes, 7o Monocytes, 7o Eosinophils, 7o Basophils, 7o 0 - 49 45 46 46 1 49 46 45 43 2 46 44 41 33 3 45 47 40 33 0 13.3 12.3 12.4 12.9 1 15.1 14.4 14.4 13.5 2 -15.8 14.8 14.3 11.7 3 15.6 14.9 13.6 10.6 0 6.63 6.38 6.23 6.51 1 7.13 6.82 6.51 6.30 2 6.74 6.81 6.57 5.44 3 6.64 6.82 6.21 5.54 0 12.64 13.72 11.73 11.72 1 9.41 .7.40 9.08 11.53 2 11.76 9.27 8.76 8.67 3 10.96 9.04 10il4 11.38 0 14 11 14 11 1 15 17 14 15 2 15 13 17 12 3 11 20 11 8 0 0 0 0 0 1 0 0 0 0 2 0 0 0 0 5 3 1 0 0 5 0 0 83 87 84 88 f2 1 81 81 84 84 .j 2 '82 83 79 87 3 85 77 88 90 '5 0 1 2 1 i 1 2 1 1 i 2 2 2 2 i Q 3 2 2 0 i ? 1.y 0 1 0 1 0 1 2 1 1 0 <g 2 1 2 2 0 & 3 1 1 1 1 ' t(a 0 0 0 0 0 S 1 0 0 0 0 2 0 0 0 0 3 0 0 0 0 * Dosage level in this group increased to 1000 ppm. in the 5th week of study. ** Dosage level in this group increased to 5000 ppm. in the 5th week of study. TABLE 14. Ninet:7-Day Feeding ?Study in the Rat. Indiv idual Rat Hemal:ologic Value s during Con)trol Perio d. Rat No. & Sex Hematocrit % Hemoglobin 1Erythrocytes gms./lOO ml. (xloS/cmrn.) Total Leucocytes (xlO^cinin.) Neutroiphils Seg.7o Ncin-Seg.7o DifJferential Lymphocyfce;s Monocyte 7o 7, Control: 14163M 46 12.6 6.09 7.29 7 1 92 0 14167M 50 14.0 6.90 14.00 13 0 84 3 14173M 45 12.3 6.42 12.82 31 0 69 0 14175M 46 12.7 6.01 10.32 9 2 85 4 14178M 48 12.6 6.94 11.52 21 1 78 0 14181M 45 12.0 5.91 8.57 9 0 91 0 Mean 47 12.7 6.38 10.75 15 1 83 1 14143F 48 13.2 6.14 16.18 9 0 90 1 14146F 48 12.5 6.14 12.34 19 0 80 1 14150F 48 13.2 6.89 14.18 20 0 75 3 14154F 50 13.9 6.98 13.03 8 0 91 1 14157F 49 13.1 6.40 9.74 7 0 92 0 14160F 49 13.6 7.22 10.38 21 0 78 0 Mean 49 13.3 6.63 12.64 14 0 84 1 100 ppm. : 14204M 49 13.4 6.50 9.65 16 0 78 4 14208M 43 13.4 5.40 8.63 15 0 84 1 14210M 44 12.1 6.20 12.96 16 2 81 0 14205M 43 12.2 5.81 7.36 19 1 78 1 14216M 45 12.0 6.10 6.44 13 0 87 0 14220M 46 12.9 6.23 14.36 8 0 90 1 Mean 45 12.7 6.04 9.90 15 1 82 1 14184F 46 12.1 6.02 25.67 15 0 81 4 14189F 41 11.1 5.55 14.31 14 0 84 1 14191F 45 12.0 6.07 10.55 6 0 92 2 14194F 46 12.6 6.25 10.63 5 0 95 0 14198F 45 11.7 6.02 9.78 11 0 85 3 1420 IF 49 14.1 8.36 11.40 14 0 84 2 Mean 45 12.3 6.38 13.72 11 0 87 2 --------b ' ;ct^ormrttpnaon^yiir S<iaenmiittii7zae^dl. rD\ro>easc nrwoit fcnonnttsain TCSrC'AA 1C(-BHa Company SanA./^d. i-o..^ .. -.i c: ;a ;; T ^ Ninety -Day Feieding tStudy in the Rat TABLE 1.4. Continued. Ind ividua 1 Rat Hematologi c Values during Cont:rol Perilod. Rat No. & Sex Henlatocrit % HeTOogI obin :Erythrocytes gms./lO 0 ml. (xlO^cinni,) Total Le ucocytes Neutror>hils (x 10^/cmm.) Seg.% Nori-Seg.% Dif:Eerential ]Lymp'bocyties Monocytes % % 500 ppm.: 14244M 45 11. 5 6.33 10.25 22 0 77 0 14247M 44 12. 3 6.66 13.42 21 0 78 1 14249M 45 12. 3 6.02 12.58 5 0 94 0 14251M 47 13. 0 6.22 10.76 15 0 82 3 142 5 5M 43 12. 1 6.04 10.19 16 0 81 2 14257M 46 12. 6 5.99 17.68 10 0 88 1 Mean 45 12. 3 6.21 12.48 15 0 83 1 14225F 48 13. 3 6.74 23.52 24 0 75 1 14227F 47 11.3 5.83 9.47 10 0 88 1 142 3 IF 44 12.8 6.51 10.19 10 0 89 1 14233F 45 12.5 6.15. 10.35 8 0 90 2 14236F 45 12.4 6.13 8.58 19 0 79 0 14241F 45 12.0 6.01 8.26 15 0 82 2 Mean 46 12.4 6.23 11.73 14 0 84 1 2500 ppm. 14284M 44 12 .5 6.03 15.14 18 1 79 2 14288M 46 12 .9 6.48 10.32 12 0 88 0 14290M 44 12 .4 6.01 13.88 10 1 87 1 14295M 43 12 .3 5.72 8.92 11 0 86 2 142 98M 42 12 .0 6.22 10.30 13 1 85 0 14301M 44 12 .0 5.77 9.21 8 0 90 2 Mean 44 12 .4 6.04 11.30 12 1 85 1 14264F 46 13 .0 6.25 11.62 13 1 85 1 14267F 46 12 .9 6.58 11.10 7 0 91 2 14269P 45 12 .2 6.13 8.96 11 0 87 1 14276F 51 13 .7 6.76 11.35 9 1 89 0 14278F 43 12 .2 7.16 17.47 8 0 90 2 14281F 45 13 .4 6.20 9.84 18 0 81 1 Mean 46 12 .9 6.51 11,72 11 0 88 1 company Sanitized . Does not contain TSCA CBI TABLE Rat No. & Sex Ninetyi^-Day Feeding Study :in the Rat 15. Indiv:i-dual Rat Hem.atologLc Values a .t One Mpnti1. Hem atocrit % Hemoglobin Erythr ocytes gins. /100 ml. (x!06 /cmm.) Total Lemcocytes Neutro phils (aLlOS/cinm.) !Seg.% No n-Seg.7o . Diff erential L ympHocyteis Monocyte 7, % Control: 14162M 50 U165M 46 14168M 47 14171M 47 14174M 48 14177M 47 Mean 48 14142F 48 14144F 48 14146F 50 14148F 51 1415QF 47 14153F 49 Mean 49 15.4 7. 18 14.40 8 0 86 5 13.9 6. 66 14.75 6 0 91 3 14.8 6. 80 9.27 6 0 90 3 14.5 6. 22 14.34 5 0 94 1 14.4 6. 44 10.88 7 0 92 1 14.5 6. 30 7.08 10 0 88 1 14.6 6. 60 11.79 7 0 90 2 14.7 6. 87 7.82 14 0 82 1 15.2 7. 04 8.80 19 0 77 1 15.5 8. 12 11.60 18 0 77 3 15.2 7.27 10.53 17 0 80 - 1 14.3 6.61 7,00 14 0 80 3 15.4 6.89 10,72 9 0 89 1 15.1 7.13 9.41 15 0 81 2 100 ppm.: 14202M 44 14205M 48 14208M 47 14211M 45 14214M 49 14217M 45 Mean 46 13.6 6 .32 19.70 . 7 0 90 1 14.8 6 .73 7.10 25 0 74 0 14.6 7 .08 8.22 30 0 69 0 13.7 6 .54 6.78 9 0 88 1 13.8 7 .03 11.69 23 0 76 0 14.1 6 .72 13.77 7 0 92 1 14.1 6 .74 11.21 17 0 82 0 14182F 47 14185F 44 14188F 46 14191F 48 14194F 45 14197F 46 Mean 46 14.2 6 .69 9.15 6 0 91 1 13.6 6 .68 3.97 46 3 49 1 14.3 6 .91 8.64 11 0 87 0 14.8 7 .10 6.98 18 0 81 1 13.9 7 .28 6.53 11 0 86 2 14.4 6 .30 9.15 8 0 91 1 14.4 6 .82 7.40 17 0 81 1 te^^^^ ^J^I^^^^^^^^^^^^B San.tized.Do^not^3'"^^81 Soinpany TABLE V,ii ^ NinetyDay Feeding Study in the Rat, Con tin ued. Individiial Rat: HE'matologic Valiues at One M(anfch. Rat. No, & Sex I leuiafcocr:Lt % Hemoglobin Erytl-irocytes gins./LOO ml, <xlC>6/cTOm.) T ota:1 Leuc ocyifces (xlO 3/cinm. ) Neutirophols Seg.7, I ^onSeg.% 500 ppm, 14242M 51 1.42 45M 45 15.9 7 .07 7 .48 17 0 14248M 47 13.6 6 .03 7 .84 14 1 14.6 6 .77 9 .75 9 0 1144225541.MM 4476 13.9 6 .17 11 .62 12 0 142 5 7M 48 14.7 5 .99 8 .16 10 0 Mean 47 14.5 6 ,55 8 .13 ( 20 0 14.5 6 .43 8 .83 14 0 14222F 45 14.4 6 .55 11 .49 8 0 1422.5F 46 14228F 45 14.3 6 .83 9 .65 10 0 14.4 6 .20 7 .68 11 0 14231F 45 14234F 46 14.2 6 .42 9 .95 21 1 14.4 6 .69 5 .79 20 0 14237F 45 Mean 45 14.5 6 .35 9 .90 14 0 14.4 6 .51 9 .08 14 0 2500 ppTO 14282M 42 14285M 44 13.2 6 .02 9 .79 8 0 13.9 6 .57 11,,49 11 0 14288M 42 14291M 45 12.6 5 .93 8 ,82 9 0 142 94M 41 13.7 6 .68 6,,71 18 0 12.5 6 .14 6,,54 11 0 M14e2a9n7M 4435 13.9 6 .50 8,,34 10 0 13.3 6 .31 8.,62 11 0 14262F 44 14265F 42 13.6 6 .12 19,,29 9 0 14268F 46 13.3 6 .07 9.,08 16 0 14.6 7 .19 6. 28 14 0 14271F 41 14274F 40 13.0 5,,96 13. 43 18 0 14277F 44 12.9 5,,95 8. 84 16 0 13.8 6,,53 12. 23 16 1 Mean 43 13.5 6.,30 11. 53 15 0 Dif:ere ntial Lymptiocyti58 'Monocytes % % 82 0 84 1 90 1 87 1 90 0 79 0 85 1 90 2 89 1 87 0 77 1. 79 1 83 1 84 1 91 0 88 1 90 1 82 0 85 3 89 0 87 1 88 3 83 1 - 85 0 80 1 83 1 81 2 84 1 gprw""IV 5gr>{trf. DOBS not contain T8CAC01 TABLE 16. Ninet)^Day Fe eding Study in the Rat IndiviLdual Ra t Hen.atologi c Values a t Two Mon ths, Rat No. & Sex Hem atocrifc 7, Hemogi obin Erythr ocytes gms./10'0 ml. (xl06 /cmm.) Total Le ucocytes Neutro phils (x lO^cum.) Seg.'% No nSeg.% 1 Differen tial Lympt'%iocytes Mo;no%cyte Control: 14164M 47 14167M 49 14170M 52 14174M 47 14178M 47 14181M 48 Mean, 48 '14143F 47 1.4147F 48 14149P 49 14152F 41 14154F 50 14158F 42 Mean 46 15. 4 7, 02 11.44 7 0 90 2 16. 5 7. 43 13.95 12 0 83 5 16. 6 7. 47 11.11 5 0 93 1 15. 6 7. 07 9.73 31 0 64 5 16. 0 7. 00 11.22 19 0 81 0 15. 4 7. 24 9.88 8 0 90 2 15. 9 7. 21 11.22 14 0 83 3 15.4 6. 67 11.86 32 0 67 1 16. 2 6. 78 15.15 9 0 87 3 16.4 7. 26 10.64 9 0 88 1 15. ,2 6. 36 10.92 22 0 78 0 15.8 7. 03 12.83 7 0 90 3 16.0 6. 31 9.16 8 0 90 2 15.8 6. 74 11.76 15 0 82 2 100 ppm.: 14204M 50 14210M 44 14213M 41 14217M 42 14220M 50 14221M 40 Mean 45 16 .0 7.84 10.75 19 0 75 3 14 .9 7.55 9.29 8 0 90 1 14 .8 7.87 12.15 14 0 84 1 14 .9 6.84 7.30 8 0 91 1 15 .8 8.02 9.37 15 0 82 2 14 .5 7.20 7.56 12 0 85 3 15 .2 7 .55 9.40 13 0 84 2 14184F 45 14190F 45 14193F 41 14194F 44 14196F 43 14200F 43 Mean 44 15 .2 6 .85 10.00 7 0 90 1 15 .0 6 .74 6.42 22 2 69 4 13 .6 6 .12 7,11 10 0 87 2 15 .1 6 .71 6.23 12 0 83 3 15 .1 6 .98 13.75 14 0 85 0 14 .5 7 .47 12.12 10 0 90 0 14 .8 6 .81 9.27 13 0 83 2 J----|^^^ ^^^^^^^^^^^^^f ^^^mH^u^^r , Qomoany Sanitized. Does not eonlsun TSGA GBt TABLE Rat No. 6; Sex Ninet;y-'Day 'Feeding Sfc udy in the R at. 3-6. Continuied. Individual Rat Hematolo gic Values at Two Mont hs . Hem.2ttocrit % Hemoglobin Er ythrocytes gais./lOO ml. ( xlO^/cmm.) Total Leucocytes Neutrop hits (xlO^/cmm, ) Seg.7. Non -Seg.% Difi^erential Lymphocyteis Monocyte % % 1000 ppm. : 14243M 42 .14246M 46 14251M 47 142 5 3M 46 14257M 46 142 61M 42 Mean 45 142 2 3F 42 14226F 43 14230F 41 14234F 37 14237F 43 14240F 38 Mean 41 15.4 7.71 9.97 23 0 75 1 15.2 7.11 12.04 13 0 84 1 15.4 7.42 12.47 11 0 87 1 14.8 6.94 8.86 15 1 82 1 15.9 8.03 10.67. 6 0 93 0 15.1 6.89 13.43 13 1 82 2 15.3 7.35 11.24 14 0 84 1 15.5 7.28 8.34 16 1 81 0 14.2 6.63 6.64 18 0 72 5 14.3 6.28 10.28 8 0 92 0 13.6 6.63 6.17 24 0 74 1 15.8 6.85 13.43 28 0 62 8 12.4 5.77 7.68 6 0 94 0 14.3 6.57 8.76 17 0 79 2 5000 ppm.: 14283M 42 14289M 34 14293M 35 14295M 36 14297M 38 14300M 44 Mean 38 13.3 6.33 11.96 7 0 92 0 12.0 6.12 17.50 23 0 76 1 12.3 6.09 11.20 17 0 81 1 12.7 6.13 6.97 8 0 91 0 13.6 6.08 14.49 4 0 94 1 15.0 6.96 9.46 9 1 87 3 13.2 6.29 11.93 11 0 87 1 14263F 37 14270F 29 14273F 35 14275F 33 14279F 30 14281F 33 Mean 33 13.0 5.60 11.57 10 1 87 2 11.2 5.31 5.16 14 0 84 2 12.1 5.64 9.55 8 0 91 1 11.8 5.47 8.90 8 0 92 0 10.4 4.93 6.78 17 0 81 1 11.7 5.68 10.07 17 0 82 0 11.7 5.44 8.67 12 0 87 1 i ^ ^ ^^^^^^^^^^^^^^^^^^^^^^^B i^ompariy Sanitized. Does noit contain TSCA C01 TABLE Rat No. & Sex N:Lnety-Day Feedin g Study in the Rat. 17. I-ndividual Rat Hematologi c Value-s at Three M onths, Hematoc rit % Hemoglobini Erythr ocytes gms./100 ml.. (xlo6 /cmm.) 1 Total Leucocytes (xlO^/cinm.) Neutroph ils Seg.% Non-;Seg.% Diff erential Lymphocyte!S Monocyte % % Control: 14164M 53 14169M 46 14172M 47 14176M 48 14179M 47 14181M 50 Mean 48 14147F 46 14151F 43 14154F 45 14156F 41 14158F 47 14161F 45 Mean 45 100 ppm.: 14203M 45 14206M 50 14210M 47 14215M 46 14218M 46 14219M 50 Mean 47 14183F 49 14186F 50 14190F 38 14195F 49 14197F 50 14200F 46 Mean 47 16.1 7. 52 17.93 15 0 82 3 16.0 6. 68 21.59 6 0 94 0 15.6 7. 14 14.62 23 0 70 5 15.6 6. 79 13.86 15 0 84 1 15.2 7. 53 10.06 17 0 80 1 15.6 7. 10 13.45 24 0 74 2 15.7 7.16 15.25 17 0 80 2 16.9 6..64 13.71 7 1 89 2 15.1 6..52 7.16 18 2 80 0 15.2 6.,66 12.03 15 1 79 1 15.1 6,,33 7.12 9 1 88 1 16.0 7.02 11.53 5 0 91 2 15.2 6.69 14.18 13 0 84 2 15.6 6.64 10.96 11 1 85 1 14.5 6 .60 13.85 40 1 58 1 15.2 7 .47 10.73 . 24 0 73 0 14.8 6 .91 9.58 7 0 91 0 15.1 6 .80 7.47 20 1 78 0 14.6 6 .90 12.35 16 0 82 0 15.6 7 .60 7.71 12 0 87 0 15.0 7 .05 10.28 20 0 78 0 15.6 6 .89 12.16 13 0 85 2 li 15.3 7 .26 10.83 29 0 69 1 12.0 6 .09 6.65 28 3 63 3 15.9 6 .89 5.57 0 87 1 16.0 6 .77 11.79 15 0 85 0 14.8 7 .03 7.25 26 0 73 1 14.9 6 .82 9.04 20 0 77 2 Company Sanitized. Does not contain TSCA CBS Ninety -Day Feieding Study in the Rat TABLE 1--7 Continue,d. Ind ividusil Rat Hematologi c Values <a t Three M onths. Rat No. & Sex Henistocrit % Hemogi obin Erythrocytes gms./lO 0 ml. (xlO^cmni.) Total Le ucocytes Neutro phils (x 103/cmm.) Seg.% No n-Seg.% Difife'rential LympHiocyttis Monocytes '7, 7o 500 ppm.: 14244M 48 14247M 45 14252M 47 14255M 44 14257M 46 14260M 43 Mean 45 15. 6 7.59 8.18 7 0 92 0 14. 4 6.91 10.44 23 0 74 0 15. 1 7.28 8.53 9 0 90 0 13. 9 6.48 11.35 12 0 86 0 15. 0 7.27 12.50 31 0 68 1 14. 0 6.82 15.89 13 0 84 2 14. 7 7.06 11.15 16 0 82 1 14224F 43 14227F 36 14232F 41 14236F 45 14238F 39 14240F 38 Mean 40 14. 2 6.14 9.40 6 0 93 0 12. 7 6.07 12.13 18 0 82 0 14.6 6.52 12.63 16 0 84 0 14.6 6.39 7.02 13 0 87 0 12..8 6.22 9.94 6 0 94 0 12.6 5.90 9.70 8 0 89 1 13.6 6.21 10.14 11 0 88 0 i 2500 ppm. 14283M 38 14287M 35 142 91M 37 14294M 35 14297M 41 14300M 41 Mean 38 12 .1 6.20 13.87 6 0 93 1 11 .8 5.29 8.41 8 0 91 0 11 .9 5.82 10.18 7 0 92 1 11 .0 5.15 12.18 11 1 84 0 11 .8 6.19 13.55 4 0 94 1 13 .4 6.73 11.12 13 1 79 4 12 .0 5.90 11.55 8 0 89 1 14266F 31 14269F 34 14272F 36 14276F 34 14278F 30 14281F 36 Mean 33 9 .7 5.25 13.37 8 0 91 0 10 .5 5.04 13.63 8 1 89 2 11 .6 6.38 8.95 10 0 88 2 10 .5 5.54 9.45 8 1 89 1 9 .5 5.42 14.55 2 0 95 2 12 .0 5.63 8.35 10 0 88 1 10 .6 5.54 11.38 8 0 90 1 " S.nl.lz^oe-no.con.alnTSCACB. comply Page 44 Ninety-Day Feeding Study in the Rat. TABLE 18. Group Individual and Mean Results of Biochemical Studies During Control Period Rat No. Alkalime Phosphatase SGOT1 SGPT2 Control, Female 14142 78 14145 78 .14149 75 14153 105 14156 93 14154 45 14144 14147 14152 14155 14158 14160 Mean 79 . 34 24 27 24 29 23 28 23 28 23 30 25 29 24 Control, Male 14162 99 14164 93 14166 57 14172 93 14177 93 14179 99 14170 29 23 14168 30 22 14174 31 24 14176 27 22 14180 32 23 14171 29 26 Mean 89 30 23 100 ppm., Female 14183 36 14188 48 14192 39 14199 48 14182 90 14196 45 14185 14190 14193 14200 14197 14195 Mean 51 ^ Serum Glutamic Oxalacetic Transaminase 26 22 29 23 29 22 29 25 29 24 29 24 29 23 Serum Glutaaic Pyruvic Transaminase Does not contain TSCAC81 Company eS.annuil.izzpeda. >-'" Page 45 ^^^^H Ninety-Day Feeding Study in the Rat. TABLE 18. Group Continued. Individu al and Mean Results of Bioch(imical Studies During Control Period. Rat No Alkaline Phosphatase SGOT1 SGPT2 100 ppm.. Male Mean 14202 14209 14211 14219 14214 14221 14203 14206 14212 14215 14218 14217 57 87 - 63 93 96 36 72 29 23 27 23 30 23 29 23 26 24 30 26 29 23 . 500 ppm.. Female 14230 90 14224 87 14222 84 14240 96 14235 99 14232 90 14229 29 24 14228 25 22 14223 29 22 14239 30 22 14237 28 25 14234 27 22 Mean 91 28 23 500 ppm.. Male 14242 51 14245 57 14248 54 14252 93 14254 39 14258 87 14243 27 22 14246 29 22 14250 26 24 14253 29 22 14256 27 22 14259 25 23 Mean 64 27 22 Serum Glutamic Oxalacetic Transaminase Serum Glutamic Pvruvic Transaminase ^nTpsriy Sannizea. Doss noico. ,,.,.,;; i-BCA Page 46 Ninety-Day Feeding Study in the Rat. TABLE 18. Continued. Individual and Mean Results of Biochemical Studies During Control Period Group Rat No. Alkaline Phosphatase SGOT1 SGPT2 2500 ppm. , Mean Female 14271 14266 14262 14273 14274 14277 14268 14265 14263 14272 14275 14280 39 75 57 * 99 78 69 27 22 32 24 28 21 31 24 28 23 29 23 70 29 23 2500 ppm. , Male 14282 90 14286 90 14296 51 14283 51 14289 93 14297 48 14287 32 27 14291 27 25 14300 26 24 14285 29 22 14292 29 23 14299 27 21 Mean 71 Serum Glutamic Oxalacetic Transaminase n Serum Glutamic Pyruvic Transaminase Company Sanitized. Does not contain TSCA C91 Page 47 Ninety-Day Feeding Study in the Rat. TABLE 19. Group Individual and Mean Results of Biochemical Studies at One Month. Rat No. Alkaline Phosphatase SGOT1 SGPT2 Control, Female 14143 60 26 24 14145 84 28 25 14147 90 25 23 14149 78 26 25 14151 96 24 23 14154 72 28 25 Mean 80 26 24 Control, Male 14163 72 14166 53 14169 129 14172 63 14175 114 14178 129 Mean 93 25 24 24 21 25 24 28 23 27 24 24 24 26 23 100 ppm., Female 14183 45 14186 75 14189 117 14192 54 14195 108 14198 114 Mean 86 26 23 26 24 25 24 25 22 25 23 25 24 25 23 100 ppm.. Male 14203 84 14206 129 14209 132 14212 105 14215 105 14218 126 Mean 114 25 24 27 25 27 24 26 23 26 24 25 23 26 24 500 ppm., Female 14223 52 14226 99 14229 84 14232 117 14235 123 14238 102 Mean 96 28 25 28 25 26 23 27 23 28 26 26 25 27 25 Serum Glutamic Oxalacetic Transaminase ^ ^ Serum Glufcamic Pyruvic Transaminase Company Sanitized. Doss rw cont, ai. n ,,T.S-C,,,A. C-,BBEI Page 48 ^^^^^1 Ninety-Day Feeding Study in the Rat. TABLE 19. Continued. Individual and Mean Results of Bioche:mical Studies at One Month. Group Rat No Alkaline Phosphatase SGOT1 SGPT2 500 ppm., Male 14243 72 14246 132 14249 132 14252 96 14255 87 14258 132 Mean 109 27 23 27 25 26 24 26 24 25 23 25 25 26 24 2500 ppm.. Female 14263 84 28 24 14266 51 27 24 14269 60 26 23 14272 72 28 24 14275 84 28 24 14278 45 28 25 Mean 66 28 24 2500 ppm.. Male 14283 72 14286 117 14289 117 14292 69 14295 105 14298 81 Mean 94 28 23 27 24 24 23 25 23 26 23 25 24 26 24 Serum Glutamic Oxalacetic Transaminase Serum Glutamic Pyruvic Transaminase Company Sanitized. Doss not contain TSCA CB8 Page 49 Ninety-Day Feeding Study in the Rat. TABLE 20. Group Individual and Mean Results of Biochemical Studies at Two Months. Rat No Alkaline Phosphatase SGOT1 SGPT2 Control, Female 14144 60 27 21 14148 73 26 24 .14150 59 25 22 14151 56 19 22 14153 67 25 22 14155 67 26 22 Mean 64 25 22 Control, Male 14163 54 28 20 14166 38 28 23 14169 79 26 23 14171 98 27 24 14172 78 24 24 14173 78 25 22 Mean 71 26 23 100 ppm.. Female 14183 31 24 21 14186 47 23 23 14187 58 25 22 14192 39 24 21 14195 36 30 22 14198 37 29 22 Mean 41 26 22 100 ppm., Male 14203 56 14206 36 14209 111 14211 64 14216 33 14219 46 Mean 58 25 24 28 21 27 22 27 22 29 24 29 23 28 23 1000 ppm.. Female 14224 62 26 21 14227 58 27 22 14229 64 29 24 14232 63 26 22 14235 46 31 22 14236 27 25 21 Mean 53 27 22 Serum Glutamic Oxalacetic Transaminase Serum Glutamic Pyruvic Transaminase Company Sanded. Does notconiain TSCA cm Page 50 ^^H Ninety-Day Feeding Study in the Rat. TABLE 20. Continued. Individual and Mean Results of Biochemical Studies at Two Months. Group Rat No. Alkaline Phosphatase SGOT1 SGPT2 1000 ppm.. Male 14242 39 14247 45 26 23 27 22 14249 53 29 21 14254 41 26 23 14256 38 29 21 14259 70 28 22 Mean 48 28 22 5000 ppm,. Female 14264 64 27 20 14267 32 27 21 14269 32 26 21 14271 36 27 21 14274 28 29 21 14277 37 28 22 Mean 40 27 21 5000 ppm.. Male 14284 47 26 23 14289 49 27 21 14292 82 27 21 14294 27 27 20 14296 50 29 24 14298 88 28 23 Mean 57 27 22 Serum Glutamic Oxalacetic Transaminase Serum Glutamic Pyruvic Transaminase Company Sanitized. Does not contain TSCACBi Page 51 TABLE 21. Group Ninety-Day Feeding Study in the Rat. Individual and Mean Results of Biochemical Studies at Three Months. Rat No. Alkaline Phosphatase SGOT1 SGPT2 Control, Female Mean 14144 14248 14155 14157 14159 14160 26 30 23 59 - 23 24 21 26 22 20 28 22 31 27 23 28 28 26 31 27 23 Control, Male 14174 24 14171 30 14173 32 14175 79 14177 77 14180 107 Mean 58 26 21 26 23 27 22 25 25 27 24 28 27 27 24 100 ppm., Female 14187 22 25 22 14189 29 26 23 14192 18 25 21 14196 14 22 21 14198 68 23 22 14199 32 24 21 Mean 31 24 22 100 ppm.. Male 14204 16 24 22 14207 25 23 21 14209 47 26 20 14211 25 25 21 14213 35 24 21 14216 41 22 22 Mean 32 24 21 1000 ppm.. Female 14226 39 23 24 14229 53 26 24 14233 73 25 23 14235 55 25 25 14237 50 25 22 14239 22 23 20 Mean 49 25 23 Serum Glutamic Oxalacetic Transaminase Serum Glutamic Pyruvic Transaminase Company Sanitized. Does not contain TSCA CK Page 52 ^^^^^^f Ninety-Day Feeding Study in the Rat. TAB LE 21. Group Cone inued. Individual and Mean Results of Biochemical Studies at Three Months. Rat No. Alkaline Phosphatase SGOT1 SGPT2 1000 ppm.. Male 14243 41 29 27 14250 43 25 22 14254 15 26 19 14256 26 23 20 14259 87 23 23 14261 34 22 22 Mean 41 25 22 5000 ppm., Female 14264 26 25 22 14277 19 25 21 14271 18 25 20 14274 18 26 22 14280 26 28 22 14279 16 25 19 Mean 21 26 21 5000 ppm.. Male 14284 49 27 24 14286 66 25 24 14290 37 24 21 14292 75 24 22 14296 45 24 22 14298 33 24 . 21 Mean 51 25 22 Serum Glutamic Oxalacetic Transaminase Serum Glutamic Pyruvic Transaminase Company Sanitized. Does not contain TSCA CB( 3LE 22. Ninety- Day Feeiding St:udy in t he Rat. Urinal;rsis Va]Lues foir Male anid Fema]Le Rats during C ontirol Period. Microsco it i. ;Sex itro 1: L43 F 1.46 F -50 F -54 F -57 F -60 F .63 M .67 M .73 M .75 M .78 M .81 M ^Volume (ml.) 5 12 3 5 6 6 21 1 1 4 2 12 f ippearance Si?ecific pH Gi:avity S;C 7.0 LS;cl 6.9 S;cl 6.3 S;C 6.8 S;C 7.0 S;C 7.2 LS;C 6.5 Am;C 6.4 LAm;C 6.2 S;cl 6.8 S;cl 6.4 LS;C 9.0 1.028 1.030 1.032 1.032 1.032 1.030 1.030 1.063 1.065 1.040 1.045 1.030 Albu min N N N N N N N 3+ N N N N Bili- rub in N N N N N N N N N N N N Gl u- -0 cc. co se- Bl odd' WBC RBC N N occ N N N N N N N N N N N N N oce N N N N occ N N N N Ep i. Cells F occ 1-3 Amor. Urates F F Amm. Urates F F F i ppm. : 84 F 89 F 91 F 94 F 98 F 01 F 04 M 08 M 10 M 05 M 16 M 20 M : S - LS - Am - LAm - 6 LS;cl 7 LS;cl 4 S;C 3 S;cl 13 LS;C 3 LAm;C 6 LS;cl 3 S;C 2 S;C 4 S;cl 4 LS;C 9 LS;cl Straw Light Amber Light Straw Amber 6.8 8.8 6.5 8.8 9.0 6.8 8.5 6.2 6.5 6.8 7.0 9.0 C - cl - 1.030 1.030 1.030 1.040 1.030 1.045 1.030 1.055 1.042 1.030 1.032 1.030 Clear Cloudy N N N N N N N N N N N N N N N N N N N N N N N N N N N N N N N N N N N N N N N N N N N N N N N N N - Negative 1+ - Trace-to- Slight 2+ - Slight-to -Moderate 3+ - Moderate 4+ - Marked occ F F occ F occ M occ F occ F M occ F F F M - occ - Few Many Occasional ------.swHiz.-.r LE ;>2. Ninety-Day Feeiding St udy in ttie Rat. cIontinue<3. Urir;lalysis Values f(ar Malei and Femalie Rat S du ring Ccintrol Period. ! Microsco .t \ ^lume ;Appear SF>ecific i.Mbu- Bill- Gl.u- 0 cc. Epi. Amor. Annn. L.iex (ml.) ance pH Gi-avity min rybin ccise Bl ood WBC EtBC Cells Urates Urates PP-n1^.: 25 F 1 S;C 6.3 1.045 N N N N occ 27 F 3 S;cl 8.8 1.042 N N N N 31 P 3 S;C 6.3 1.045 N N N N 33 F 3 S;cl 8.0 1.040 N N N N 36 F 7 LS;cl 6.5 1.030 N N N N 41 F 3 LAm;C 6.0 1.045 N N N N 44* M 4 S;C 6.2 1.040 N N N N 47 M 4 S.;cl 9.0 1.035 N N N N 49 M 5 S;cl 8.3 1.032 N N N N 51 M 4 S;cl 6.7 1.045 N N N N 55 M 6 LS;cl 6.7 1.030 N N N N 57 M 4 S;cl 6.5 1.042 N N N N 1-2 occ F F F F F occ , P F F M M F occ M 3 p pm. : 34 F 1 37 F 6 39 F 21 76 F 4 ''8 F 4 n F 2 54 M 2 !8 M 2 >0 M 5 >5 M 10 8 M 12 H M 1 Am;C S;cl LS;C S;cl S;C DS;C S;C S;cl S;cl LS;cl S;cl Am;C : S - LS DS Am - ^^1LAm - Straw Light Straw Dark Straw Amber Light Amber 6.5 6.9 7.0 7.3 7.4 9.0 7.0 9.0 9.0 9.0 6.9 6.2 G - cl - 1.065 1.030 1.030 1.030 1.033 1.042 1.048 1.053 1.037 1.030 1.030 1.055 Clear Cloudy N N N N N N N N N N N N N N N N N N N N N N N N N N N N N N N N N N N N' N N N N N N N N N N N N . N - Negative 1+ - Trace-to-Slight 2+ - Slight-tc5-Mpder ate 3+ - Moderate 4+ - Marked F bcc F occ occ F M F occ M M F occ occ F M L - occ - F M occ M M occ 2-3 F , M F Few * Occasiona Many Loaded O^5^^1panysanlliz.eod-. LE 23. Ninety-Day Feeiding S;tudy in tlhe Rat. Urinal ysis Va'lues f<ar Male anid Ferna:le Rats att One M[onth. Mi<;roscop k 'V^lume ;appear Ipecific .Albu Bill- Gl u- Oicc, Epi. Amor. Aiim. T ciiex (ml.) ance pH Giravity min rub in coise BLobd 1ffBG RBC Cells Urates Ur,ates t.'co ]: 62 M 12 LS;cl 8.5 1.013 N N 65 M 12 LS;cl 7.9 1.016 N .N 68 M 17 LS;cl 8.9 1.014 N N 71 M 4 LS';cl 7.2 1.048 N N 74 M 15 LS;cl 7.0 1.013 N N 77 M 9 LS;cl 6.9 1.020 N N 42 F 10 LS;cl 6.5 1.017 N N 45 F 7 S;cl 9.0 1.041 N N 46 F 15 LS;cl 7.1 1.012 N N .48 F 6 DAm;C 8.9 1.031 N N 50 F 12 LS;cl 6.2 1.011 N N 53 F 7 S;cl 6.9 1.035 N N N N N N N N N N N N N N N N N N N M N N N N N N 1-2 occ F 1-2 F occ 1-2 F F P F 1-2 F occ F > pFiin : 02 M 7 '.05 M 26 108 M 10 '11 M 16 14 M 14 -17 M 10 -82 F 4 .85 F 13 -88 F 14 .91 F 12 -94 F 7 .97 F 9 S;cl LS;cl S;cl LS;cl S;cl S;cl S;cl LS;cl LS;C LS;cl S;cl S;cl Le: S - Straw LS - Light Straw DAm - Dark Amber 7.0 1.044 7.3 1.008 6.9 1.021 9.0 1.009 6.5 1.013 6.3 1.021 7.0 1.042 7.1. 1.011 9.0 1.007 6.8 1.016 9.0 1.019 6.5 1.017 C Clear cl Cloudy N N N N N N N N , N N N N N N N N N N N N N N N N N N N N N N N - 1+ 2+ 3+ 4+ - N N N N N N N N N N N N N N N N N, N Negative Trace-to-Slight Slight-to-Moderate Moderate Marked F F F F M L - occ - occ 1-2 occ F F occ F F F occ F occ F Few Many Loaded Occasional Company Sanitized. Does not TABLE Ninety-Day Feeding Study in the Rat. ~~r----- 23. Ciantinu ed. Uriilalysi;3 Values f or Ma:Ie and Female Ralta at One Month. M[icrosc Rat No. iSex 500 ppin. ; 14242 M 14245 M 14248 M 14251 M 14254 M 14257 M 14222 F 14225 F 14228 F 14231 F 14234 F 14237 F V<alume (ml.) 12 10 12 13 16 17 8 4 6 14 3 16 Appear iSpecific ance pH (Sravity LS;cl 7.1 LS;cl 9.0 LS;cl 9.0 LS;cl 6.1 LS;cl 6.8 LS;cl 8.9 S;cl 6.5 S;cl 6.5 S;cl 6.6 S;cl 7.2 DS;cl 6.1 LS;cl 8.8 1.012 1.023 1.011 1.015 1.011 1.012 1.024 1.048 1.034 1.012 1.050 1.010 Albu min N N N. N N N N N N N N N Bili- rubin N N N N N N N N N N N N Glucose N N N N N N N N N N N N (?cc. B:Lood N N N N N N N N N N N N WBC RBC 1-2 occ Epi. Cells 1-2 1-2 occ occ Amor. Urates F F Amm. I traces F F F F F F 2500 ppm.: 14282 M 14285 M 14288 M 14291 M 14294 M 14297 M 14262 F 14265 F 14268 F 14271 F 14274 F 14277 F Code: S - LS DS - f 1 14 LS;C 7 LS;cl 17 LS;cl 14 LS;cl 4 DS;cl 17 S;cl 4 S;cl 4 S;cl 6 S;cl 15 LS;cl 14 S,cl 8 S;cl Straw Light Straw Dark Straw 7.1 7.3 8.8 9.0 8.9 6.9 7.0 6.1 6.5 7.0 6.7 7.1 C - cl - 1.023 1.035 1.015 1.012 1.042 1.014 1.044 1.040 1.025 1.011 1.013 1.017 Clear Cloudy N N N N N N N N N N N N N N N N N N N N N N N N N N N N N N N N N N N N N N N N N N N N N N N N N - Negative 1+ - Trace- to-Slight 2+ - Slight -to-Moderate 3+ - Moderate ' 4+ - Marked F 1-2 F F occ F occ F 2-3 F F occ occ F F M L - occ - Few Many Loaded Occasional Company Sanitized. D r TABLE 2 4. Ninetyr-Day Fe<iding IStudy in t;he Ratr Urina]Lysis Va:Lues fior Male aiid Fern;lie Rats sit. Two 1ton the. Microscio Rat V<olume Appear iSpecific No. iSex (ml.) ance pH (Sravity Confcro;L: 14164 M 28 LS;cl 7.0 1.015 14167 M 16 LS;cl 7.1 1.022 14170 M 12 LS;cl 7.0 1.028 14174 M 25 LS;cl 9.0 1.014 14178 M 24 LS;cl 7.5 1.012 14181 M 30 LS;cl 8.0 1.009 14143 F 6 LS;cl 7.5 1.030 14147 F 13 L3;C 7.7 1.022 14149 F 6 S;cl 9.0 1.030 14152 F 11 LS;cl 9.0 1.024 14154 F 3 S;C 6.2 1.065 14158 F 4 S;C 6.0 1.047 100 ppm. : 14204 M 14210 M 14213 M 14217 M 14220 M 14221 M 14184 F 14190 F 14193 F 14194 F 14196 F 14200 F Code: S - LS - 30 LS;C, 18 LS;cl 21 LS;cl 17 S;cl 30 LS;cl 23 LS;.cl .4 S;cl 20 LS;cl 24 LS;cl 6 S;cl 5 S;cl 8 S;cl Straw Light Straw 7.8 8.8 9.0 9.0 8.0 9.0 7.5 8.4 6.4 9.0 6.8 6.2 - C - cl - 1.016 1.022 1.016 1.015 1.008 1.011 1.044 1.008 1.006 1.028 1.028 1.030 Clear Cloudy v Albu min Bill- rub in (Slu<;ose (3cc. 'B'.Lood N N N N N N N N N N N N N N N N N N N N N N N N N N N N N N N N N N N N N N N N N N K N N N N N N N N N N N N N N N N N N N N N N N N N N N N N N N N N N N N N N N N N N N N N N N N N N N N N N - Negative 1+ - Trace-to-Slight 2+ - Slight-to-Moderate 3+ - Moderate 4+ - Marked Epi. Amor. Ainm. WBC KBG Cells Urates Uratea occ F occ F : F M M M F M F F F F occ F M occ F F F M F occ F F occ M F M M F F F F M L - occ - Few Many Loaded Occasional 'Company Sanitized. Does ^n^ ' IIT - t TABLE 2:4. Ninetyr-Day Fe eding Study in the R at. Co ntinue<i. Uriniaysis Values f(ar Mal.e and Fernale Rats at Two Months. Microsc; Rat V olume Appear Specific Albui- Bili- Glu- 0 cc. Epi- Amor. Amm. No. !Sex (ml.) ance PH Gravity mini rub in cose Bl pod[ WBC RBC CellB Urates Urates 1000- pipm. : . mi 14243 M 24 LS;cl 9.0 1.013 N N. N N F F 14246 M 16 LS;cl 6.8 1.017 N N N N F 14251 M 12 LS;cl 6.0 1.026 N N M N occ F F 14253 M 30 LS;C 7.8 1.010 N N N 1+ F M M 23 LLSS?.cclI 7:22 l:0l5 N N N N N M N N F F 14223 F 11 S;cl 7.2 1.013 N N N N F M 14226 F 10 S;cl 9.0 1.030 N N N N F 14230 F 12 LS;cl 8.8 1.016 M N N N F F 14234 F 7 S;cl 6.4 1.023 N N K N F F 14237 F 14 LS;C 7.5 1.010 N N N N F 14240 F 15 LS;el 7.8 1.009 N N N N F 5000 ppm.: 14283 M 14 LS;cl 9.0 1.021 N N N N 14289 M 27 LS;cl 9.0 1.013 N N N N 14293 M 10 S;cl 9.0 1.034 N N N N 14295 M 40 LS;cl 9.0 1.006 N N N N 14297 M 27 LS;cl 9.0 1.012 N N N N 14300 M 23 LS;cl 6.7 1.010 N N N N 14263 F 12 S;cl 7.0 1.020 N N N N 14270 F 10 S;cl 7.2 1.017 N N N N 14273 F 14 LS;cl 9.0 1.013 N N N N 14275 F 5 Am;cl 8.5 1.024 fi N N N 14279 F 8 S;C 6.0 1.026 N N N N 14281 F 4 S;C 8.2 , 1.028 N N N N M F occ F F F F F occ F F F M F F Code: S - LS Am - Straw Light Straw Amber C - d - Clear Cloudy ^ N - Negative 1+ - Trace-to-Slight 2+ - Slight-to-Moderate 3+ - Moderate 4+ - Marked F M L - occ - Few Many Loaded Occasional Company Sanitized. Does not contain ^jw} ^ w , > e ^ - Minet y-Day Fee'ding !Study in t he Ralh TABLE 25. Urineilysis Va lues f or Male arid Fern,ale Rats a t Threei Months. Microsc o Rat V olume Appear Specific Albu Bill- G:lu- C>ec. Epi. Amor. Amm. No. !3 ex (ml.) ance pH iGravity min rub in c<3se Bl,ood WBC RBC Cells Urates Urates Control1: 14164 M 14169 M 14172 M 14176 M 14179 M 14181 M 14147 F 14151 F 14154 F 14156 F 14158 F 14161 F 100 ppm.: 14203 M 14206 M 14210 M 14215 M 14218 M 14219 M 14183 F 14186 F 14190 F 14195 F 14197 F 14200 F Code: S - LS DS - r -1 8 LS;cl 1 S;cl 11 LS;cl 5 S;cl 4 S;cl 7 S;el 1 S;C 2 S;C 2 S;cl 2 S;cl 1 S;C 2 S;C 7 S;cl 7 LS;cl 6 S;cl 3 DS;cl 9 S;cl 6 LS;cl 1 S;C 6 LS;cl 6 S;cl 6 LS;cl 1 S;C 2 S;cl Straw Light Straw Dark Straw 6.8 7.3 9.0 6.5 7.8 6.9 6.1 6.3 7.4 6.1 6.0 6.7 6.7 7.0 9.0 6.0 9.0 6.3 6.0 8.0 7.0 6.2 7.7 6.0 C - cl - 1.053 1.055 1.035 1.066 1.058 1.052 1.080 1.069 1.065 1.065 1.080 1.065 1.058 1.048 1.055 1.080 1.045 1.049 1.080 1.045 1.035 1.035 1.072 1.065 Clear Cloudy N N N N N N N N N N N N N N N N N N N N N N N M N N N N N N N N N N N N N N N N N N N N N N N N N N N N N N N N N N N N N N N N N N N N N N N N N N N N N N N N N N N N N N N N N N N N N N N N N - Negative 1+ - Trace-to-Slight 2+ - Slight-to-Moderate 3+ - Moderate 4+ - Marked F F F F 1-2 F F F F F F occ F F F 1-2 F occ occ F occ F F F 2-3 F F occ F F 1-2 F F F M F F M L - occ - Few Many Loaded Occasional Company Sanitized. Does not co Ninety-Day Feeding Study in the Rat. ^ 7 TABLE 2 5. Coiitinue d. Uriniilysis Values:'f(?r Mali2; arid' Fema Ie Rat;s at Three Months. Microsc Rat V(3lume Appear Specific Albu Bill- G lu- (3cc. Epi. Amor. Amm. No. i3ex i(ml.) ance pH Gravity min rub in c ose B]Lood WBC RBG Cells Urates Urates 1000 p]:nn; : 14244 M 10 LS;cl 7.0 1.035 N N N :3+* 14247 M 6 S;cl 6.8 1.057 N N N N. . 14252 M 5 S;cl 6.6 1.065 N N N N 14255 M 4 S;C 6.0 1.065 N N N N 14257 M 10 LS;cl 9.0 1.037 N . N N 14260 M 3 S;cl 6.7 1.073 N N N M occ F 2-3 F occ F F 2-3 F 1-2 F 14224 F 14227 F 14232 F 14236 F 14238 F 14240 F 5 S;cl 9.0 1.045 N 2 S;C 6.7 1.068 N 3 S;cl 5.9 1.057 N 2 S;C 6.0 1.075 N 2 S;cl 6.5 1.065 N 1 S;C 6.2 1.078 N N N N N N N N N N occ N N N 1-2 N. N N N N N F F F F F F F 5000 ppm.: 14283 M 2 Am;Cl 6.2 1.075 N N N N occ 14287 M 4 S;cl 6.8 1.073 N N N N 14291 M 6 S;cl 8.8 1.045 2+ N N N 14294 M 2 DS;cl 7.7 1.080 N N N N 14297 M 4 DS;C 6.1 1.075 M N N N 14300 M 4 S;cl 6.8 1.065 N N N N 14266 F 14269 F 14272 F 14276 F 14278 F 14281 F 1 S;C 7.0 1.080 N 2 S;cl 6.2 1.068 N 1 DS;C 5.8 1.065 N 1 DS;C 6.6 1.065 N 2 S;C 6.3 1.065 N 1 DS;G 6.0 1.080 N N N N N N N oce N N N N N N N N N 1-2 N N N 1-2 F F F F F occ F F F F F occ F F 1-2 F F F Code: S - LS - DS - Am r IL------^ Straw Light Straw Dark Straw Amber C - Clear cl - Cloudy N - Negative 1+ - Trace-to-Slight 2+ - Slight-to-Moderate 3+ - Moderate 4+ - Marked F - Few M - Many L - Loaded occ - Occasional * Repeat 3+ Company Sanitized. Doe w TABLE 26. Animal Number Ninety-Day Feeding Study in the Rat. Necropsy Observations. Thirty-Day Interim Sacrifice, Sex Organ Comment Rats were normal except as noted below; Control: 14165 14146 100 ppm.: 14202 M 14208 M 14185 F thymus uterus lung lung uterus Pew petechial hemorrhages, Mild hydrouterus. Moderate pneumonia. Mild pneumonia. Mild hydrouterus. 2500 ppm. : 14288 M 14262 spleen spleen Slightly enlarged. Slightly enlarged. Company Sanitized. Does not contain TSCA CBI Page 62 Ninety-Day Feeding Study in the Rat. TABLE.26-. Continued. Necropsy Observations. Sixty-Day Interim Sacrifice. Animal Number Sex Organ Comment Rats were normal except as noted below: Control: 14149 100 pprn^; 14221 M 5000 ppm.: 14289 M D 14293 M 14295 M lung liver lung liver testes liver liver Few scattered gray areas. Pale. Gray pinpoint areas scattered throughout. Slightly pale. Left testis approximately twice the size of right. Pale. Pale yellow in color. Company Sanitized. Does not contain TSCA CBt Page 63 (\ Ninety-Day Feeding Study in the Rat. ^------------^------------------------------------------------------------------------------------------------------------ TABLE 2$. Continued. Necropsy Observations. Ninety-Day Terminal Sacrifice. Animal Number Sex Organ Comment Rat were normal except as noted below: Control: 14175 M 14153 F 100 DDm.: 14214 M lung lung lung Mild pneumonia. Mild pneumonia. Mild pneumonia. 1000 DDm. 14252 I 14254 14227 14233 M liver M lung F- abdominal cavity F lung 14237 F lung 5000 DDTO. 14284 M 14286 M 14291 M 14294 M 14297 M 14266 F 14274 F liver lung liver liver liver lung kidney Slightly yellowish. Mild pneumonia. 6 mm. firm hemorrhagic area in abdominal fat. Mild pneumonia. Mild pneumonia. Slight yellowish cast. Mild pneumonia. Slight yellowish cast. Slight yellowish cast. Slight yellowish cast. . Moderate pneumonia and bronchiectasis. Hydronephorsis, right kidney. Company Sanitized. Does not contain TSCA CB1 Ninety-Day Feeding Study in the Rat. -7 TABLE .26. Continued. Necropsy Observations. 21-Day Compound Withdrawal. Animal Number Sex Organ Comment Rats were normal except as noted below; 5000 ppm.; 14299 M 14300 M liver liver Slightly pale. Slightly pale. D Company Sanitized. Does not contafn TSCA CB1 age 65 ^ M N inety-:Day FeediLug Stud y in th e Rat. TABLE 27. Me an Actiual (Granis) and ]Etelativ'e (7o Boiiy ffeiglit) Org,an Wei)ghts. ? Dietai Leve. T ermina',1 Sex2'ody fft, Gm. ,, SFileen L:iver Adr<snals Ki(ineys Gm. 7, Gm. 7. Gin. 7. GDI. 7. Tes;tes/ Ova,ries Gm. 7. 30-Dair 0 0 100 100 500 500 2500 2500 Interim M F M F M F M F SacrijEice: 315 0.97 202 0.70 268 0.70 212 0.69 243 0.62 188 0.47 277 1.12 173 0.59 60-Day 0 0 100 100 |^000 PIOOO 5000 5000 Interim M F M F M F M F Sacrifice: 355 0.76 233 0.52 338 0.79 230 0.52 355 0.74 210 0.54 412 0.90 232 0.62 90-Day 0 0 100 100 1000 1000 5000 5000 Terminal M F M F M F M F Sacrifice: 495 1.08 270 0.71 469 1.14 284 0.81 452 0.97 284 0.77 425 0.98 237 0.81 21-Day 0 0 1000 1000 5000 5000 Compound M F M F M F Withdrawal: 490 0.70 297 0.56 507 0.91 287 0.61 440 0.61 277 0.57 0.308 0.347 0.261 0.326 0.255 0.250 0.404 0.341 14.11 8.74 11.65 7.28 10.06 8.26 15.68 8.65 4.479 4.327 4.347 3.434 4.136 4.394 5.661 5.000 0.039 0.069 0.044 0.054 0.037 0.054 0.044 0.068 0.010 0.034 0.020 0.025 0.015 0.029 0.016 0.039 2.66 1.73 2.22 1.56 2.30 1.86 2.80 1.85 0.844 0.856 0.828 0.736 0.946 0.990 1.011 1.069 2.99 0.089 2.69 0.092 2.74 0.097 2.74 0.123 0.949 0.040 1.003 0.040 1.127 0.050 0.989 0.070 0.214 0.22 0.234 0.226 0.208 0.257 0.218 0.267 13.02 8.25 10.91 8.00 12.94 7.89 21.71 12.04 3.668 3.541 3.228 3.478 3.645 3.757 5.269 5.190 0.062 0.070 0.048 0.065 0.046 0.075 0.071 .0.067 0.017 0.030 0.014 0.028 0.013 0.036 0.017 0.029 2.62 1.72 2.53 1.70 2.70 1.92 3.46 2.36 0.738 0.738 0.749 0.739 0.761 0.914 0.840 1.017 3.07 0.133 3.30 0.132 3.08 0.162 3.82 0.145 0.865 0.060 0.976 0.060 0.868 0.080 0.927 0.060 0.218 0.263 0.243 0.285 0.215 0.271 0.231 0.342 14.12 8.17 14.19 8.27 15.02 10.59 20.38 10.95 2.853 3.026 3.026 2.912 3.323 3.729 4.795 4.620 0.066 0.075 0.057 0.071 0.060 0.087 0.057 0.072 0.013 0.028 0.012 0.025 0.013 0.031 0.013 0.030 2.87 1.73 2.95 1.87 3.05 2.30 3.33 2.25 0.580 0.641 0.629 0.658 0.675 0.810 0.783 0.949 i 3.32 0.154 3.39 0.171 3.39 0.155 3.37 0.142 0.670 0.057 0.723 0.060 0.750 0.055 0.793 0.060 0.143 0.189 0.179 0.213 0.139 0.206 14.82 9.17 17.41 9.35 16.55 10.75 - 3.024 3.087 3.434 3.258 3.761 3.881 0.056 0.073 0.065 0.077 0.058 0.083 0.014 0.025 0.013 0.027 0.013 0.030 2.97 2.09 3.36 2.25 3.18 2.45 0.606 0.704 0.663 0.784 0.723 0.884 3.36 0.224 3.59 0.177 3.32 0.162 0.686 0.080 0.709 0.060 0.755 0.060 Company Sanitized. Does not contain TSCA CBI Page 66 T hymus Heart Lune Th'yroid B:rain Pit<jitary Gm. 7. Gm. 7, Gm. . 7. Gm. % Gm.. 7. Gm. 7. : 0.90 0.286 1.15 0.365 1.63 0.517 0.023 0.007 1.86 0.591 0.009 0.003 0.68 0.337 0.78 0.386 1.32 0.653 0.021 0.010 1.79 0.886 0.007 0.003 0.73 0,272 0.98 0.366 1.56 0.582 0.027 0.010 1.74 0.649 0.009 0.003 : 0.47 0.222 0.69 0.325 1.25 0.590 0.018 0.008 1.74 0.820 0.009 0.004 0.67 0.276 0.94 0.386 1.58 0.650 0.024 0.010 1.84 0.757 0.008 0.003 0.71 0.378 0.77 0.410 1.28 0.681 0.024 0.013 1.74 0.926 0.008 0.004 0.74 0.267 1.06 0.383 1.65 0.596 0.018 0.006 1.96 0.708 0,006 0.002 0.59 0.341 0.68 0.393 1.34 0.774 0.018 0.010 1.80 1.040 0.004 0.002 ^ V 0.64 0.57 0.79 0.50 0.66 0.56 0.90 0.56 0.180 0.244 0.234 0.217 0.186 0.267 0.218 0.241 1.41 0.86 1.17 0.76 1.09 0.81 1.36 0.85 0.397 0.369 0.346 0.330 0.307 0.386 0.330 0.366 1.91 1.16 1.70 1.44 1.92 1.41 2.06 1.34 0.538 0.498 0.503 0.626 0.501 0.671 0.500 0.578 0.026 0.024 0.027 0.036 0.022 0.033 0.030 0.025 0.007 0.010 0.008 0.016 0.007 0.016 0.007 0.011 1.61 1.79 1.88 1.75 2.00 1.87 1.98 1.86 0.454 0.768 0.556 0.761 0.563 0.890 0.481 0.802 0.014 0.011 0.010 0.012 0.010 0.010 0.012 0.013 0.004 0.005 0.003 0.005 0.003 0.005 0.003 0.006 0.66 0.51 0.64 0.52 0.59 0.50 0.66 0.50 0.130 0.189 0.136 0.183 0.131 0.176 0.155 0.211 1.37 0.84 1.42 0.87 1.32 0.98 1.29 0.85 0.277 0.311 0.303 0.306 0.292 0.345 0.304 0.359 2.02 1.37 2.11 1.40 2.08 1.48 1.91 1.54 0.408 0.507 0.450 0.493 0.460 0.521 0.449 0.650 0.028 0.025 0.027 0.024 0.028 0.031 0.025 0.022 0.006 0.009 0.006 0.008 0.006 0.011 0.006 0.009 1.92 1.82 1.99 1.87 1.96 1.89 2.00 1.85 0.388 0.674 0.424 0.658 0.434 0.665 0.471 0.781 0.014 0.013 0.011 0.013 0.013 0.013 0.010 0.010 0.003 0.005 0.002 0.005 0.003 0.005 0.002 0.004 0.79 0.52 0.84 0.58 0.67 0.62 0.161 0.175 0.166 0.202 0.152 0.224 1.32 0.89 1.51 0.84 1.28 0.93 0.269 0.300 0.298 0.293 0.291 0.336 2.47 1.53 2.29 1.63 1.82 1.60 0.504 0.515 0.452 0.568 0.414 0.578 0.035 0.026 0.036 0.029 0.030 0.030 0.007 0.009 0.007 0.010 0.007 0.010 2.07 1.87 2.12 1.95 2.01 1.90 0.422 0.630 0.418 0.680 0.457 0.686 0.010 0.012 0.014 0.014 0.012 0.012 0.002 0.004 0.003 0.005 0.003 0.005 W ,^ 0 Company Sanitized. Does not contain TSCA CBI ^u ^ "TABLE 28/ '(inety-Da>y Feedin g Study in the Ra t. )rgan Wei.ghts, Gr ams Animal ^Cerminal Testes/ No. & Weight Spleen Liver Adrenals Kidneys Ovaries Thymus Heart Lung 'Thyroid B Group S ex Grams 30-DAY INTERI14 SACRIF]^CE: Control: 14162 M 14165 M 14168 M 14142 F 14145 F 14146 F 100 ppm.: 14202 M 14205 M 14208 M 14182 F 14185 F 14188 F 500 ppm.: 14242 M 14245 M 14248 M 14222 F 14225 F 14228 F 2500 ppm , ; 14282 M 14285 M 14288 M 14262 F 14265 F 14268 F 270 360 315 205 175 225 275 300 230 280 190 165 225 270 235 205 160 200 255 290 285 195 170 155 1.09 0.92 0.89 0.52 0.99 0.60 12.02 17.02 13.30 8.63 8.11 9.49 0.024 0.051 0.043 0.079 0.056 0.071 0.94 0.67 0.50 0.57 1.10 0.40 12.51 13.42 9.02 7.75 7.81 6.28 0.044 0.050 0.038 0.060 0.053 0.048 0.49 0.79 0.59 0.50 0.40 0.50 9.49 11.02 9.66 9.20 7.08 8.51 0.028 0.046 0.036 0.052 0.051 0.060 0.71 0.90 1.76 0.99 0.47 0.32 14.75 15.29 16.99 10.35 7.78 7.82 0.061 0.051 0.019 0.079 0.056 0.068 2.35 3.11 2.52 1.79 1.50 1.91 2.39 2.41 1.86 1.61 1.67 1.42 2.16 2.52 2.21 1.96 1.59 2.04 2.49 2.90 3.00 2.12 1.70 1.74 3.06 2.81 3.10 0.084 0.063 0.120 2.76 3.11 2.19 0.110 0.092 0.075 2.83 2.82 2.56 0.084 0.083 0.123 2.29 2.83 3.10 0.100 0.117 0.153 0.75 0.90 1.44 0.020 1 0.93 1.43 1.68 0.024 1 1.01 1.12 1.76 0.025 1 0.79 0.79 1.30 0.022 8 0.53 0.71 1.22 0.020 1 0.71 0.85 1.45 0.021 1 0.81 0.93 1.84 0.025 1 0.69 1.07 1.47 0.027 1 0.70 0.93 1.37 0.029 1 0.60 0.72 1.30 0.030 1 0.41 0.65 1.36 0.012 1 0.39 0.70 1.08 0.012 1 0.50 0.99 1.76 0.033 1 0.93 1.03 1.60 0.023 2 0.58 0.79 1.38 0.016 1 0.80 0.81 1.31 0.028 1 0.45 0.70 1.14 0.026 1 0.87 0.80 1.38 0.018 1 0.65 0.96 1.46 0.026 1 0.88 1.02 1.40 0.019 2 0.70 1.20 2.08 0.010 1 0.67 0.76 1.41 0.021 0.61 0.65 1.14 0.013 0.50 0.63 1.47 0.020 Company Sanitized. Does not contain TSCA C TABLE ^ Ninety-Dciy 2.8. Coiatinued. Fee din g Study in the Rat Organ 1Weights, Grams. Animal Terminal No. & Weight Spleen Group t5ex Grams 21-DAY CC)MR.O UND WITHDI^AWAL: Control: 14177 M 14179 M 14180 M 14158 F 14159 F 14161 F 1000 ppm 14258 M 14259 M 14260 M 14238 F 14239 F 14240 F 5000 ppm 14298 M 14299 M 14300 M 14278 F 14279 F 142SO F 420 520 530 280 320 290 560 470 490 280 290 290 340 535 445 280 260 290 / 0.60 0.65 0.85 0.42 0.53 0.73 1.05 0.63 1.05 0.68 0.57 0.59 0.55 0.78 0.50 0.57 0.53 0.62 Liver .Adrenals 11.80 14.98 17.68 8.48 9.34 9.70 0.050 0.064 0.055 0.071 0.072 0.075 18.65 17'.40 16.17 8.90 9.63 9.52 0.064 0.068 0.062 0.081 0.069 0.081 11.10 22.95 15.61 11.10 10.13 11.01 0.051 0.074 0.048 0.087 0.085 0.077 Kidneys 2.67 3.02 3.22 1.98 2.15 2.15 3.65 3.20 3.23 2.26 2.40 2.09 2.80 3.75 2.98 2.30 2.52 2.52 r Cestes/ (Dvaries 3.30 3.29 3.50 0.185 0.248 0.239 3.80 3.55 3.41 0.180 0.192 0.160 3.32 3.40 3.25 0.124 0.160 0.203 Thvmus 0.58 0.88 0.90 0.41 0.64 0.51 0.90 0.83 0.80 0.52 0.61 0.60 0.58 0.75 0.68 0.61 0.60 0.65 Heart 1.18 1.41 1.38 0.93 0.90 0.85 1.70 1.41 1.41 0.80 0.91 0.82 1.05 1.60 1.20 0.88 0.92 1.00 Lung 'Thyroid 2.43 2.23 2.75 1.57 1.50 1.52 0.030 0.034 0.042 0.041 0.018 0.020 2.23 2.30 2.34 2.11 1.42 1.35 0.035 0.034 0.038 0.027 0.023 0.037 1.64 2.09 1.72 1.70 1.32 1.78 0.018 0.044 0.028 0.029 0.034 0.028 Bra 2.2 2.0 1.9 1.8 1.9 1.9 2.1 2.0 2.2 1.9 1.8 2.0 2.0 2.1 1.9 1.7 1.9 1.9 Company Sanitized. Does not contain TSCA CBI v n 'Ninety-Day Feed in g Study in the Rat ^ABLE 28. Cont inued. Organ Weights, Grams. Animal No. & Group 60-DAY Ti erminal Weight S ex Grams Spleen INTERIM SACRII'ICE: Liver Adrenals Kidneys Control: 14167 M 14170 M 14178 M 14143 F 14149 F 14152 F 100 ppm.: 14217 M 14220 M 14221 M 14184 F 14193 F 14194 F 1000 pom.: 14246 M 14251 M 14253 M 14223 F 14230 F 14234 F 5000 ppm . 14289 M 14293 M 14295 M 14263 F 14270 F 14275 F C- . 340 0.81 13.13 0.058 385 0.71 14.70 0.069 340 0.75 11.24 0.059 200 0.49 7.28 0.059 260 0.47 8.88 0.071 240 0.59 8.58 0.080 325 0.79 11.78 0.051 340 0.79 10.52 0.053 350 0.79 10.44 0.041 215 0.41 0.062 235 0.54 8.29 0.064 240 - 0.61 7.70 0.069 320 0.62 11.75 0.050 360 0.79 14.00 0.048 385 0.81 13.08 0.041 215 0.55 8.24 0.081 220 0.65 8.01 0.076 195 0.41 7.42 0.068 450 0.71 26.05 0.070 355 1.34 16.75 0.067 430 0.66 22.33 0.075 265 0.50 13.71 0.074 200 0.55 10.29 0.063 230 0.80 12.11 0.065 2.60 2.90 2.36 1.55 1.90 1.71 2.69 2.31 2.59 1.61 1.66 1.82 2.57 3.09 2.45 1.89 2.01 1.85 3.49 3.33 3.56 2.46 2.20 2.41 Testes/ Ovaries T hvmus 3.14 2.89 3.19 0.170 0.100 0.130 0.69 0.70 0.52 0.49 0.69 0.53 3.32 3.31 3.27 0.144 0.135 0.118 0.83 0.96 0.59 0.45 0.47 0.58 2.70 3.17 3.37 0.138 0.200 0.149 0.60 0.62 0.77 0.58 0.50 0.60 1.69, 2.95 3.32 3.49 0.168 0.079 0.188 1.00 0.91 0.78 0.68 0.50 0.50 Heart 1.16 1.48 1.58 0.75 0.98 0.84 1.13 1.22 1.15 0.70 0.80 0.78 1.12 1.11 1.05 0.89 0.88 0.66 1.40 1.38 1.29 0.87 0.80 0.89 Lung 'Thyroid 1.67 2.03 2.02 1.07 1.22 1.19 0.027 0.027 0.025 0.015 0.031 0.027 1.60 1.81 1.69 1.15 1.78 1.38 0.037 0.025 0.019 0.044 0.023 0.042 1.95 1.81 2.01 1.40 1.62 1.21 0.024 0.029 0.014 0.042 0.038 0.018 1.89 2.19 2.11 1.29 1.44 1.30 0.029 0.036 0.025 0.021 0.033 0.022 Brain 1.81 1.20 1.81 1.87 1.74 1.75 2.01 1.71 1.92 1.79 1.73 1.73 1.91 1.99 2.09 1.82 1.90 1.90 1.90 1.96 2.08 1.80 1.88 1.90 Company Sanitized. Does not contain TSCA CBI t - YNinety-Daiy Feeding; Study in the Rat TABLE 28 Cont inued. Organ W<iights, Grams. Animal No. & Group 1Terminal Weight Sex Grams Spleen 90-DAY r CERMINAL SACRI1TTCF, : Control 14163 M 14164 M 14166 M 14169 M 141.71 M 14172 M 14173 M 14174 M 14175 M 14176 M 14144 F 14147 F 14148 F 14150 F 14151 F 14153 F 14154 F 14155 F 14156 F 14157 F 410 545 420 460 430 490 800 450 545 400 325 255 280 300 250 255 275 255 290 210 1.10 1.22 0.91 1.11 1.32 1.10 0.99 1.00 1.28 0.75 1.00 0.51 0.76 0.75 0.71 0.69 0.72 0.81 0.78 0.39 Liver Adrenals 11.63 17.92 12.83 14.18 13.81 15.47 11.91 15.12 17.71 10.48 9.90 7.11 8.62 9.80 7.50 7.88 8.39 8.32 8.63 5.58 0.061 0.059 0.053 0.063 0.066 0.078 0.058 0.080 0.065 0.081 0.096 0.065 0.060 0.084 0.051 0.080 0.078 0.090 0.090 0.055 Kidneys r Cestes/ (ovaries 2.29 2.80 3.71 3.58 2.51 3.22 3.10 3.65 2.79 3.37 3.10 3.19 2.39 3.15 3.02 3.31 3.12 3.49 2.65 3.42 2.49 0.242 1.52 0.134 1.70 0.155 ' 1.92 0.167 1.61 0.104 1.58 0.147 1.72 0.140 1.60 0.170 1.89 0.154 1.23 0.123 Thymus 0.52 1.09 0.43 0.71 0.59 0.95 0.41 0.69 0.60 0.58 0.60 0.52 0.39 0.51 0.60 0.60 0.51 0.53 0.38 0.41 Heart 1.22 1.90 1.13 1.23 1.40 1.38 1.12 1.38 1.58 1.39 1.05 0.80 0.71 0.98 0.75 0.83 0.78 0.85 0.89 0.73 Lung T' hyroid 2.00 2.38 1.64 1.78 2.09 2.07 2.03 1.60 2.92 1.68 1.71 1.00 1.35 1.52 1.21 1.61 1.48 1.37 1.40 1.05 0.040 0.051 0.019 0.036 0.021 0.024 0.020 0.019 0.026 0.025 0.031 0.015 0.024 0.031 0.031 0.023 0.030 0.024 0.023 0.018 Bra 1.8 2.0 1.8 2.0 1.8 1.9 1.8 1.8 2.0 2.0 1.8 1.7 1.8 1.9 1.6 1.8 1. 1.8 1.8 1.8 Company Sanitized. Does not contain TSCA CBI ^B?) ^ - TA-BIE 28 . Sinety-Daiy Feedinig Study :i.n the Rat Con tinued. Organ \heights, Grams. animal To. & 3rouD l rerminal Weight Sex Grams Spleen 90-DAY r CERMINAL SACRII?ICE: LOO poni, ^ 14203 M 1.4204 M 14206 M 14207 M 14209 M 14210 M l42].l M 1.4213 M 14214 M 1421.5 M 14216 M 14218 M 14219 M 14183 F 14186 F 14187 F 14189 F 14190 F 14191 F 14192 F 14195 F 14196 F 14197 F 14198 F 14199 F 14200 F 14201 F 455 560 465 435 400 520 470 380 485 420 535 520 450 310 345 280 265 255 290 245 280 270 260 295 280 285 310 1.49 0.99 1.20 1.20 1.21 1.24 1.48 1.03 1.02 0.70 0.90 1.41 1.00 0.64 0.81 0.81 1.10 0.70 1.22 0.68 0.71 0.89 0.54 1.00 0.76 0.81 0.68 Liver 1Adrenals 1.4.08 17.48 14.60 12.02 12.07 15.48 13.78 11.20 14.03 12.49 15.90 17.65 13.65 8.78 9.62 8.00 8.40 7.58 7.51 7.58 8.50 8.59 7.32 8.40 8.83 8.80 7.88 0.051 0.061 0.067 0.060 0.054 0.053 0.035 0.051 0.061. 0.056 0.055 0.081 0.055 0.076 0.093 0.074 0.081 0.067 0.061 0.069 0.093 0.064 0.049 0.055 0.050 0.077 0.084 Kidneys 2.50 3.38 3.25 3.05 2.72 2.79 3.10 2.61 2.89 2.80 3.29 3.02 2.95 1.93 2.15 1.77 1.91 1.58 1.96 1.80 2.01 1.80 1.72 1.79 1.81 1.98 1.99 Testes/ Ovaries 3.05 3.70 3.50 3.93 3.19 3.10 3.42 3.43 3.50 3.33 3.32 3.74 2.85 0.210 0.203 0.186 0.183 0.165 0.168 0.161 0.161 0.177 0.116 0.181 0.170 0.119 0.198 r Ehymus 0.41 0.60 0.60 0.82 0.44 1.11 0.36 0.58 0.60 0.90 0.59 0.72 0.54 0.50 0.58 0.44 0.81 0.33 0.56 0.30 0.60 0.48 0.49 0.42 0.61 0.71 0.48 Heart 1.43 1.73 1.38 1.22 1.28 1.39 1.43 1.20 1.46 1.30 1.50 1.71 1.40 0.80 1.14 0.79 0.83 0.71 0.92 0.72 0.93 0.89 0.88 0.79 1.01 0.81 0.93 Lung T' hyroid 2.28 2.10 2.72 1.74 1.90 2.20 1.95 1.62 2.71 2.08 2.02 2.21 1.90 1.52 1.34 1.21 1.42 1.29 1.43 1.43 1.30 1.53 1.28 1.60 1.41 1.37 1.50 0.019 0.025 0.024 0.023 0.025 0.021 0.039 0.027 0.028 0.036 0.022 0.029 0.028 0.034 0.026 0.027 0.023 0.016 0.023 0.026 0.028 0.022 0.014 0.019 0.023 0.020 Brain 1.85 1.93 2.08 2.08 1.82 1.90 2.19 2.09 2.09 2.00 1.97 1.83 2.08 1.78 2.02 1.90 1.73 1.75 1.89 1.91 1.88 1.92 1.77 1.92 1.81 1.87 2.09 Company San^d. Does not contain TSCA CBI ^ \^ H^^H^y\ Ninety-Day Feeding Study in the Rat. ^-AbLE 2'.Q. kontinued. Organ 1Weights;, Grams. Animal No. & Group Terminal Weight Sex Grams Spleen 90-DAY TERMINAL SACRIE'ICE: 1000 ppm.: 14243 M 14244 M 14247 M 14249 M 14250 M 14252 M 14254 M. 14255 M L4256 M 14257 M 14224 F 14226 F 14227 F 14229 F 14231 F 14232 F 14233 F 14235 F 14236 F 14237 F 455 535 475 470 440 470 460 410 385 415 290 270 295 305 320 280 230 325 275 250 1.09 0.97 0.99 1.17 0.89 0.79 1.18 1.00 1.01 0.63 0.69 0.51 0.50 0.89 0.77 0.77 1.22 0.84 0.61 0.88 Liver Adrenals 12.68 17.13 16.20 15.88 16.13 16.61 15.50 12.80 12.39 14.90 12.38 8.91 9.40 10.75 11.55 11.00 14.39 8.'14 10.52 8.81 0.054 0.065 0.053 0.082 0.057 0.067 0.058 0.053 0.055 0.055 0.107 0.066 0.073 0.075 0.097 0.096 0.116 Missed 0.074 0.077 Kidneys 2.87 3.51 3.00 3.21 3.01 3.42 3.23 2.60 2.58 3.03 2.60 2.21 2.49 2.10 2.55 2.17 2.89 1.73 2.21 2.08 Testes/ Ovaries 3.39 3.60 3.40 3.58 3.30 3.80 3.41 3.30 2.81 3.29 0.172 0.097 0.127 0.186 0.206 0.201 0.171 0.130 0.144 0.117 ^ 0.27 0.98 0.41 0.68 0.42 0.60 0.59 0.79 0.35 0.78 0.40 0.22 0.35 0.61 0.37 0.80 0.68 0.31 0.50 0.75 Heart 1.30 1.50 1.31 1.51 1.32 1.39 1.31 1.21 1.10 1.21 0.90 1.40 0.85 0.98 1.09 0.88 1.12 0.70 0.91 1.00 Lung Thyroid Brai 1.92 2.94 2.21 1.65 1.98 1.93 2.75 2.00 1.71 1.68 1.49 1.39 1.52 1.35 1.83 1.24 1.65 1.20 1.33 1.79 0.019 0.026 0.031 0.034 0.031 0.029 0.017 0.026 0.024 0.040 0.027 0.037 Missed Missed 0.026 0.040 0.031 0.022 0.028 0.034 1.82 1.98 2.25 1.93 1.91 1.89 1.81 2.01 1.98 1.99 1.81 1.89 1.90 1.91 2.08 1.90 1.99 1.68 1.9 1.85 Company Sanitized. Does not contain TSCA CBI  / \I Ninety-Day Feeding Study in the Rat. TAbLE 2i3. Con.tinued. Organ Weights, Grams. Animal Terminal No. & Weight Spleen Group Sex Grams 90-DAY :CERM-N?AL SACRI]FICF,: 1000 DDlm. : 14243 M 14244 M: 14247 M 14249 M 142.50 M. 14252 M 14254 M 1425.5 M 1.4256 M 14257 M 14224 F 14226 F 14227 F 14229 F 14231 F 14232 F 14233 F 14235 F 14236 F 14237 F 455 .535 475 470 440 470 460 410 385 415 290 270 295 305 320 280 230 325 275 250 1.09 0.97 0.99 1.17 0.89 0.79 1.18 1.00 1.01 0.63 0.69 0.51 0.50 0.89 0.77 0.77 1.22 0.84 0.61 0.88 Liver Adrenals 12.68 17.13 1.6.20 15.88 16.13 16.61 15.50 12.80 12;39 14.90 12.38 8.91 9.40 10.75 11.55 11.00 14.39 8.14 10.52 8.81 0.054 0.065 0.053 0.082 0.057 0.067 0.058 0.053 0.055 0.055 0.107 0.066 0.073 0.075 0.097 0.096 0.116 Missed 0.074 0.077 Kidneys 2.87 3.51 3.00 3.21 3.01 3.42 3.23 2.60 2.58 3.03 2.60 2.21 2.49 2.10 2.55 2.17 2.89 1.73 2.21 2.08 Testes/ Ovaries 3.39 3.60 3.40 3.58 3.30 3.80 3.41 3.30 2.81 3.29 0.172 0.097 0.127 0.186 0.206 0.201 0.171 0.130 0.144 0.117 Thvmus 0.27 0.98 0.41 0.68 0.42 0.60 0.59 0.79 0.35 0.78 0.40 0.22 0.35 0.61 0.37 . 0.80 0.68 0.31 0.50 0.75 Heart 1.30 1.50 1.31 1.51 1.32 1.39 1.31 1.21 1.10 1.21 0.90 1.40 0.85 0.98 1.09 0.88 1.12 0.70 0.91 1.00 LU]Elg Thyroid Brai 1. 92 2. 94 2. 21 1. 65 1. 98 1. 93 2. 75 2. 00 1. 71 1. 68 1. 49 1. 39 1. 52 1. 35 1. 83 1. 24 1. 65 1. 20 1.33 1.79 0.019 0.026 0.031 0.034 0.031 0.029 0.017 0.026 0.024 0.040 0.027 0.037 Missed Missed 0.026 0.040 0.031 0.022 0.028 0.034 1.82 1.98 2.25 1.93 1.91 1.89 1.81 2.01 1.98 1.99 1.81 1.89 1.90 1.91 2.08 1.9 1.99 1.6 1.9 1.8 ( Company Sanitized. Does not contain TSCA CBI V -^) TABLE ^ Ninety-Daiy 2;8. Coritinued. Fee ding Study in the Ra t. Organ 'Weights,, Grams. Animal No. & Group Terminal Weight Sex Grams Spleen 90-DAY TERMII'1AL SACRI1?ICE: 5000 corn.: 14283 M 14284 M 14286 M 14287 M 14290 M 14291 M 14292 M 14294 M 14296 M 14297 M 14264 F 14266 F 14267 F 14269 F 14271 F 14272 F 14273 F 14274 F 14276 F 14277 F 420 525 345 425 430 410 390 395 430 480 220 225 250 220 270 215 240 240 250 235 1.30 1.02 0.98 1.11 0.90 0.51 1.19 0.77 1.12 0.91 0.90 0.83 0.48 0.58 1.08 0.67 0.70 1.51 0.48 0.83 Liver Adrenals 19.57 0.058 25.68 0.065 15.13 0.059 20.11 0.050 21.49 0.059 21.65 0.060 19.82 0.050 18.30 0.054 19.82 0.054 22.19 0.058 9.84 0.063 11.40 0.077 10.85 0.067 11.01 0.068 11.91 0.072 9.57 0.083 11.75 0.062 10.41 . 0.059 11.30 0.085 11.41 0.079 Kidneys 3.30 3.91 2.62 3.30 3.38 3.18 3.20 3.30 3.31 3.80 2.00 2.03 2.28 2.25 2.78 1.80 2.38 2.45 2.12 2.40 ^ ; '-A.--' Testes/ Ovaries Thvmus 3.30 2.87 3.21 3.39 3.60 3.20 3.49 3.40 3:60 3.61 0.146 0.122 0.178 0.092 0.130 0.180 0.107 0.144 0.182 0.58 1.32 0.69 0.80 0.42 0.59 0.63 0.30 0.79 0.51 0.41 0.58 0.53 0.57 0.58 0.42 0.51 0.43 0.48 Heart 1.21 1.43 0.91 1.30 1.58 1.17 1.20 1.38 1.42 1.28 0.78 0.80 0.72 0.83 0.98 0.70 0.90 0.83 1.03 0.95 Lung Thyroid 1.88 2.35 2.18 1.98 1.61 2.02 1.42 2.09 1.60 1.92 1.38 2.93 1.28 1.13 1.40 ^.32 1.21 1.60 1.61 1.51 0.024 0.035 0.023 0.029 0.027 0.031 0.019 0.021 0.023 0.017 0.020 0.018 0.019 0.024 0.018 0.032 0.018 0.015 0.031 0.025 Brain 2.04 2.09 2.08 2.10 1.92 1.83 2.02 1.90 1.92 2.05 1.78 1.88 1.80 1.91 1.79 1.91 1.98 1.81 1.81 1.78 ^ Company Sanitised. Does not contain TSCA CBI Page 74 ^H^BBf) Ninety-Day Feeding Study 1.n the Rat. TABLE 29. Incidence of Histopathologic Lesions. Tissue and Lesion 3C1 Day Intiirim Sacri:ice Con1trol 2503 ppm. M F M F 6() Day Tn;terim Sacri fi PP Conitrol 5000 ppm. M F M F brain - no lesion 3/3 3/3 3/3 3/3 3/3 3/3 3/3 3/3 - glial nodules spinal cord - no lesion 3/3 3/3 2/2 3/3 3/3 3/3 3/3 3/3 peripheral nerve - no lesion eye - no lesion 3/3 3/3 3/3 3/3 3/3 3/3 3/3 3/3 3/3 3/3 3/3 3/3 3/3 3/3 3/3 2/2 pituitary - no lesion thyroid - no lesion 2/2 3/3 111 1/1 3/3 111 3/3 2/2 : 3/3 3/3 3/3 3/3 3/3 3/3 3/3 3/3 parathyroid - no lesion 1/1 3/3 3/3 111 1/1 ; adrenal - no lesion 3/3 3/3 3/3 3/3 3/3 3/3 3/3 3/3 ) - ossification lung - no lesion 3/3 2/3 3/3 2/3 3/3 2/3 3/3 3/3 ' - chronic respiratory disease heart - no lesion 1/3 1/3 1/3 3/3 3/3 3/3 3/3 3/3 3/3 3/3 3/3 - arteritis spleen - no lesion 3/3 3/3 2/3 3/3 3/3 3/3 3/3 3/3 - hematopoesis 1/3 lymph node - no lesion 3/3 3/3 3/3 3/3 2/2 3/3 3/3 3/3 thymus - no lesion 3/3 3/3 3/3 3/3 3/3 3/3 3/3 3/3 bone marrow - no lesion 3/3 3/3 3/3 3/3 3/3 3/3 3/3 3/3 salivary gland - no lesion 3/3 3/3 3/3 3/3 3/3 111 3/3 3/3 stomach - no lesion small intestine - no lesion 3/3 3/3 3/3 3/3 3/3 3/3 3/3 3/3 3/3 3/3 3/3 3/3 3/3 3/3 3/3 3/3 large intestine - no lesion 3/3 3/3 3/3 3/3 3/3 3/3 2/3 3/3 - nematodes 1/3 Company Sanitized. Does not contain TSCA CB1 Coiatrol M F 913 Day T(irmina:1 Sacr Ifice 1000 ppm., 500C1 ppm. M F M F 10/10 10/10 9/10 10/10 1/10 8/8 9/9 9/9 9/9 9/9 9/9 9/9 8/8 10/10 9/9 9/9 9/9 9/9 3/3 8/8 1/1 10/10 9/9 10/10 9/9 5/5 6/6 3/3 111 10/10 10/10 9/10 10/10 1. 5/10 9/10 1/10 7/10 7/10 5/10 1/10 3/10 3/10 9/10 1/10 10/10 10/10 10/10 ck 10/10 10/10 9/9 10/10 21 Day Witheirawa;1 Con trol M P 500(3 M ppm. F 3/3 3/3 3/3 3/3 3/3 3/3 3/3 3/3 3/3 3/3 3/3 3/3 3/3 3/3 3/3 3/3 3/3 3/3 3/3 3/3 3/3 3/3 3/3 3/3 1/1 1/1 3/3 1/1 3/3 3/3 3/3 3/3 2/3 1/3 2/3 1/3 1/3 2/3 1/3 2/3 3/3 3/3 3/3 3/3 3/3 3/3 3/3 3/3 9/9 9/9 10/10 9/9 10/10 10/10 10/10 8/8 9/9 10/10 9/9 10/10 10/10 10/10 8/8 10/10 9/9 8/8 9/9 10/10 9/9 - 8/8 10/10 10/10 10/10 10/10 10/10 9/10 1/10 3/3 111 3/3 3/3 3/3 3/3 3/3 3/3 3/3 3/3 3/3 3/3 3/3 3/3 3/3 3/3 3/3 3/3 3/3 3/3 3/3 3/3 3/3 3/3 3/3 3/3 3/3 3/3 I) Company Sanitized. Does not contain TSCA CB1 Page 75 ?.age 76 Ninety-Day Feeding Study in the Rat. 'ABLE 28. Continued. Tissue and Lesion Incidence of Histopathologic Lesions. 30 Day Interim Sacrifice Control 2500 ppm. M F M F 60 Day Interim Sacrifice Control 5000 ppm. M F M F pancreas - no lesion 3/3 3/3 3/3 3/3 3/3 3/3 3/3 3/3 pancreatitis, focal liver - no lesion - portal inflammatory infiltrate - centrelobular change kidney - no lesion 2/3 3/3 0/3 2/3 2/3 2/3 0/3 0/3 1/3 1/3 1/3 1/3 1/3 1/3 3/3 3/3 2/2 3/3 3/3 3/3 2/3 3/3 3/3 3/3 3/3 - focal nephritis 1/3 - hyaline droplets urinary bladder - no lesion 1"^ - siminal plug fy' Cestes or ovaries - no lesion - edema 2/3 3/3 3/3 3/3 3/3 3/3 3/3 3/3 1/3 3/3 3/3 3/3 3/3 3/3 3/3 2/3 3/3 1/3 prostate or uterus - no lesion 3/3 3/3 3/3 3/3 3/3 3/3 3/3 3/3 - hydrometra skeletal muscle - no lesion 3/3 3/3 3/3 3/3 3/3 3/3 3/3 3/3 skin - no lesion 3/3 3/3 3/3 3/3 3/3 3/3 3/3 3/3 bone - no lesion 3/3 3/3 3/3 3/3 3/3 3/3 3/3 3/3 Company Sanitized. Does not contain TSCA CBI Control M F 90 Day Terminal Sacrifice 1000 ppm. 5000 M F M ppm. F 10/10 10/10 10/10 10/10 7/10 3/10 1/10 8/10 5/10 5/10 10/10 2/10 6/8 |2/8 rO/10 9/9 10/10 7/10 3/10 6/10 4/10 1/10 1/10 9/10 10/10 10/10 10/10 2/10 8/10 2/10 9/10 1/10 9/9 10/10 10/10 9/9 9/9 10/10 9/10 1/10 10/10 10/10 10/10 10/10 10/10 10/10 9/9 10/10 9/9 6/6 10/10 21 Day Withdrawal Control 5000 M F M ppm. F 2/3 3/3 3/3 3/3 1/3 2/3 2/3 0/3 0/3 1/3 1/3 1/3 3/3 2/3 3/3 3/3 3/3 2/3 1/3 1/2 3/3 3/3 3/3 1/2 3/3 3/3 3/3 3/3 3/3 3/3 2/2 2/2 3/3 3/3 3/3 3/3 3/3 3/3 3/3 3/3 3/3 3/3 3/3 3/3 Page 77 Company Sanitized. Does not contain TSCA CBI Page 78 ------------9N)inety-Day Feeding Study in the Rat. TABLE 3d. Hisi;opathologic Obser-vations. Thirty-Day Interim Sacrifice. Animal Number Sex Tissue Comment Control: 14162 M 14165 M 14168 M 14142 F 14145 F 14146 F 2500 ppm. : 14282 M 14285 M 14288 M 14262 F 14265 F 14268 F liver urinary bladder lung Mild portal lymphocytic infiltrate. No lesion. Seminal plug. No lesion ... Small focus of pneumonic consolidation. No lesion. liver liver liver spleen liver kidney lung Slight hypertrophy of centrolobular hepatocytes. Slight hypertrophy of centrolobular hepatocytes with loss of coarse cytoplasmic granularity. Slight hypertrophy of centrolobular hepatocytes with loss of usual coarse granularity. ' Moderate hematopoetic activity. ' Mild portal lymphocytic infiltrate. Mild focal interstitial lymphocytic infiltrate. Moderate peribronchial lymphoid hyperplasia. No lesion. ^ t) Company Sanitized. Does not contain TSCA CBI Page 79 Ninety-Day Feeding Study in the Rat. TABLE 30. Continued. Histopathologic Observations. Sixty-Day Interim Sacrifice. Animal Number Sex Tissue Comment Control: 14167 M 14170 M 14178 M 14143 F 14149 F 14152 F 5000 ppm.: 14289 M 14293 M 14295 M 14263 14270 14275 liver liver lung No lesion. No lesion. Slight portal lymphocytic infiltrate. No lesion. Slight portal lymphocytic infiltrate. Few small scattered foci of pneumonic No lesion. consolidation. large intestine liver liver liver liver liver liver Nematodes. One testis was edematous and had reduced spermatogenic activity. Hypertrophy of hepatocytes which was more pronounced in the centrolobular area; hepatocytes appeared to have higher glycogen content than controls. Moderate hypertrophy of hepatocytes,. predominately centrolobular with loss of coarse granularity. Moderate portal lymphocytic infiltrate with scattered small nodules of proliferated reticuloendothelial cells in liver parenchyma. Hypertrophy of hepatocytes, primarily centrolobular, hepatocytes appeared to contain more glycogen than control. Slight hypertrophy of hepatocytes, predominately centrolobular. Slight portal lymphocytic infiltrate. Slight hypertrophy of centrolobular hepatocytes. Company Sanitized. Does not contain TSCA CBI Page 80 ^^^^^^1 Ninety-Day Feeding Study in the Rat. TABLE 39, Continued. Histopathologic Observations. Ninety-Day Terminal Sacrifice. Animal Number Sex Tissue Comment Control: 14163 M lung Moderate perivascular lymphocytic cuffing. 14164 M urinary bladder Seminal plug. 14166 M . . . No lesion. 14169 14171 14172 14173 14174 14175 14176 14144 14147 14148 M kidney liver Small numbers of hyaline droplets in epithelium of convoluted tubules. Slight portal lymphocytic infiltrate and bile duct proliferation. M lung Moderate perivascular lymphocytic cuffing with localized pneumonitis. M urinary bladder Seminal plug. lung Slight perivascular lymphocytic cuffing, peribronchial lymphoid hyperplasia. M lung kidney Slight peribronchial lymphoid hyperplasia. Moderate numbers of hyaline droplets in epithelium of convoluted tubules. M Mo lesion. M liver lung Slight portal lymphocytic infiltrate, centrolobular hepatocytes less coarsely granular. Slight perivascular lymphocytic cuffing. M liver heart Slight portal lymphocytic infiltrate. Moderate mural necrosis and perivascular inflammatory infiltrate of a coronary vessel. F No lesion. F No lesion. F liver Slight portal lymphocytic infiltrate and bile duct proliferation. ^^^'^D^nof^,,,^ Page 81 Ninety-Day Feeding Study in the Rat. TABLE 30. Continued. Histopathologic Observations. Ninety-Day Terminal Sacrifice, Animal Number Sex Tissue Comment Control (cont'd): 14150 F 14151 F 14153 F 14154 F 14155 14156 14157 liver lung liver uterus liver liver No lesion. Slight portal lymphocytic infiltrate. Small area of chronic pneumonitis. Slight portal lymphocytic infiltrate, Hydometra. Slight portal lymphocytic infiltrate. Slight portal lymphocytic infiltrate. No lesion. No lesion. com^ Sanded. Does ^^mrscACBl Page 82 Ninety-Day Feeding Study in the Rat. TABLE 30. Continued. Histopathologic Observations . Ninety-Day Terminal Sacrifice. Animal Number Sex Tissue Comment 1000 pom.. Liver Only: 14243 M 14244 M 14247 M 14249 M 14250 M 14252 M 14254 M 14255 M 14256 M 14257 M 14224 F 14226 F 14227 F 14229 F 14231 F 14232 F 14233 F 14235 F 14236 F . 14237 F No lesion. No lesion. Slight portal lymphocytic infiltrate. No lesion. No lesion. No lesion. No lesion. No lesion. Slight portal lymphocytic infiltrate. Slight portal lymphocytic infiltrate. No lesion. No lesion. No lesion. Slight portal lymphocytic infiltrate. No lesion. Slight portal lymphocytic infiltrate. Slight portal lymphocytic infiltrate. Slight portal lymphocytic infiltrate. No lesion.- . No lesion. L" IPempan^Sanitized. Does not contain JSG^G^' Page 83 Ninety-Day Feeding Study in the Rat. TABLE 30. Continued. Histopathologic Observations. Ninety-Day Terminal Sacrifice. Animal Number Sex Tissue Comment 5000 ppm.; 14283 M liver 14284 14286 M liver lung M brain lung liver 14287 M adrenal. liver 14290 14291 M M liver 14292 14294 14296 M liver lung liver liver Centrolobular hepatocytes slightly hypertrophied cytoplasm less coarsely granular than in hepatocytes at periphery of lobules. Centrolobular hepatocytes less coarsely granular than those at periphery. Slight peribronchial lymphoid hyperplasia. Glial nodules in medulla, structure resembling Sarcosporidia also present. Slight perivascular lymphocytic cuffing, area of pneumonic consolidation. Centrolobular hepatocytes less granular than those at periphery of lobule, slight portal lymphocytic infiltrate. Area of osteoid and bone in cortex of one adrenal. Cytoplasm of Centrolobular hepatocytes less coarsely granular than cytoplasm of hepatocytes at periphery, slight portal lymphocytic infiltrate. No lesion. Cytoplasm of Centrolobular hepatocytes less coarsely granular than cytoplasm of hepatocytes at periphery of lobules. Centrolobular hepatocytes less coarsely granular than those at periphery of lobules. Slight peribronchial lymphoid hyperplasia. Centrolobular hepatocytes less coarsely granular than those at periphery of lobule. Marked portal lymphocytic infiltrate, Centrolobular hepatocytes slightly less granular than those at periphery of lobule. ./'"^ ^PanyS^eci. Does ^ contain TSCA CB, Page 84 ^^^^^^^B Ninety-Day Feeding Study in the Rat. TABLE 30. Continued. Histopathologic Observations. Ninety-Day Terminal Sacrifice. Animal Number Sex Tissue Comment 5000 ppm. (cont'd) 14297 M liver 14264 14266 F liver F liver 14267 14269 14271 14272 14273 14274 lung F liver F liver F kidney liver F liver F liver large intestine F liver 14276 14277 F lung F lung Centrolobular hepatocytes less coarsely granular than those at periphery of lobule. Moderate portal lymphocytic infiltrate. Centrolobular hepatocytes less coarsely granular than those at periphery, mild portal lymphocytic infiltrate. Chronic murine pneumonia of moderate severity. Mild portal lymphocytic infiltrate. Slight portal lymphocytic infiltrate. Moderate interstitial lymphocytic infiltrate. . Mild portal lymphocytic infiltrate. Mild portal lymphocytic infiltrate. Mild portal lymphocytic infiltrate. Nematodes. Mild portal lymphocytic infiltrate, Centrolobular hepatocytes less coarsely granular than those at periphery. Moderate perivascular lymphocytic cuffing. Moderate perivascular lymphocytic cuffing. Company Sanitized, Does not contain TSCA CB Page 85 | Niniety-Day Feeding Stiidy in the Rat. TABLE 3Q Contimued. Histopatholoj^ic Observations. 21-Day Compound Withdrawal. Animal Number Sex Tissue Comment Control: 14177 M 14179 M 14180 M 14158 F 14159 F 14161 F 5000 ppm. 14298 M 14299 M 14300 M 14278 F 14279 P 14280 F pancreas lung liver urinary bladder lung liver lung No lesion. Small area of necrosis and chronic inflammation. Moderate peribronchial lymphoid hyperplasia. Slight portal lymphocytic infiltrate. Seminal plug. No lesion. Moderate peribronchial lymphoid hyperplasia. Slight portal lymphocytic infiltrate. Slight perivascular lymphocytic cuffing. liver lung urinary bladder liver liver kidney liver lung liver lung liver Slight portal lymphocytic infiltrate. Mild peribronchial lymphoid hyperplasia. Seminal plug. Centrolobular hepatocytes appeared slightly hypertrophied. Centrolobular hepatocytes appeared slightly hypertrophied. Slight interstitial lymphocytic infiltrate, few calcified tubules. Moderate lymphocytic inflammatory infiltrate, primarily in portal areas. Moderate peribronchial lymphoid hyperplasia. Mild portal lymphocytic infiltrate, few scattered vacuolated hepatocytes. Slight peribronchial lymphoid hyperplasia. Slight portal lymphocytic infiltrate. Company Sanitized. Does not contain TSCA CBA