Document dn3Dgd0p6b6jxD56KgmOOmGZG

jaJtulMal BIO-TEST 3*c. REPORT TO . MONSANTO COMPANY TWO-YEAR CHRONIC ORAL TOXICITY WITH AROCLOR 1242 IN ALBINO RATS NOVEMBER 12, 1971 ' XBT NO. B7298 L Introduction . At the request of Monsanto Company, a two-year chronic oTal toxicity study was conducted using albino rats to determine the potential - toxicity of Aroclor 1242, Lot No. AK-255. The following report presents the results of this investigation. EXHIBIT JK-Uo BBRN002174 LEXOLDMON002511 B IOT E S T Sue. 2 XL Summary A two-year chronic toxicity study was conducted using albino rats fed diets containing 1 (T-I), 10 (T-XX) or 100 (T-HI) ppm Arodor 1242. Food consumption and body weight gains were not altered at any level of'Aroclor 1242 fed. The number of animals dying and the time at which the deaths occurred did not vary among the test and control groups. Hematological and clinical blood chemistry studies conducted after 3. 6, 9, 12, 18 or 24 months did not reveal any affects related to Arodor 1242. Urine analyses failed to reveal any differences between test and control animals. . At sacrifice after 3, 6 or 12 months on test, organ weights, organ to body weight and organ to brain weight ratios disclosed several randomly occurring intergroup differences. The lack of any consistent dose related response and the absence of any deleterious histopathologic change confirm that these differences were not related to the ingestion of Arodor 1242. At the final sacrifice after 24 months on test, the liver weights and liver to body weight or brain weight ratios were significantly elevated in females from the T-XXI group. Histologic examination of the livers from fixe T-LCI group revealed several animals with vacuolar change. `This lesion is morphologically indicative of fatty degeneration. Specific fat stains confirmed the presence of fat in these vacuoles. Focal hypertrophy and focal hyperplasia were also found in the livers from animals fed Arodor 1242. 6BRN002175 LEXOLDMON002512 SuLuiiial BIO T E S T Jh\ni>t<w, 5*c. 3 * Hyperplasia of the urinary bladder was found in animala from the control group and from each of the test groups. This hyperplasia was usually associated with cystitis. The incidences and types of all tumors were about the same in all groups, including the control group, and are considered normal for rats of this age. * Respectfully submitted! INDUSTRIAL BIO-TEST LABORATORIES, INC. Report prepared by: Philip SV Smith, B. S. Assistant Toxicologist Rat Toxicity Report approved by: a>\, w Jinnies B. Plank Senior Group Leader Rat Toxicity Section Head, Toxicology M. L. Keplinger, Manager, Toxicology November 12, J971 limbbthpdcjl BBRN0D217& LEXOLDMON002513 $nuii\ial B I O T E S T tn6n*ntmiu, Sne. 4 IIL Procedure A. Experimental Animals The animal employed in the teat were Charlea River train* albino rata. Four hundred rata (200 male and 200 female) were aelected for the experiment, ear-punched with the animal number assigned and houaed individually in atandard wire-bottomed steel rat cagea. Each cage bore a color-coded card identifying the rat with reapect to project number, dietary level aaaignment, individual animal number and aex. B. Organization of Groupa A atruetural outline of the experiment ia given in Table I. TABLE 1 TEST MATERIAL: Aroelor 1242 Two-Year Chronic Oral Toxicity Study Albino Rata ' * **-*<" of Experiment Group Number of Animale Male Female Dietary Level (pom) Control . 50 50 None Administered T-I 50 . 50 1 T-II . ' 50 50 10 T-ni 50 50 - 100 * Charlea River Breeding Laboratoriea, North Wilmington, Maaa. GBRND02177 LEXOLDMON002514 SttdtU&uai B 1 O * T S T /aLWmnf, 5 C. Diets, Feeding and Food Consumption . All diets wsrs prepared in the central diet room of this laboratory* The basic ration from which all diets were constructed was a standard, pulverised stock rat ration*. The diet for any given test group was prepared by blending the calculated amount of Aroclor e 1242 with a pre-weighed portion of the stock ration in a Hobart mixer. Fresh diets were prepared each week and every rat was offered an amount of food sufficient for ad libitum feeding. Food consumption was recorded for five rats of each sex in every group weekly for the first three months and monthly for the next nine * months. Thereafter, periodic spot checks were made. . D. Body Weights and Weight Gains __ Initially, the body weight of each rat in every group was deter* mined and recorded. Thereafter, individual weighings were made weekly for the first 13 weeks and monthly thereafter until the conclusion of the investigation. E. Mortality and Reactions Checks for mortality and abnormal behavioral reactions were made daily throughout the investigation. * F. Hematologic Studies and Urine Analyses Blood studies, including determinations of hemoglobin concentra tion, hematocrit value, erythrocyte count and both total and differential * Purina Rat Chow, Ralston Purina Company, St. Louis, Missouri. GBRN00217B LEXOLDMON002515 leukocyte counts, were conducted upon five male* end five females from both the control and 100 ppm groups. . j Urine analyses for the presence of glucose, albumin, micro scopic elements, and determinations of pH and specific gravity were con ducted upon urine samples at the same time intervals and from the same animals as those employed for the blood studies. These studies were conducted after 3, 6, 9, 12, 18, and 24 months of feeding. C. Clinical Blood Chemistry Studies . Determinations of blood urea nitrogen concentration (BUN), a serum alkaline phosphatase activity (SAP), fasted blood glucose concen tration and serum glutamic-pyruvic transaminase activity (SCPT) were conducted after 3, 6, 9, 12, 18, and 24 months of feeding upon the same rats as were the routine blood studies. H. Pathologic Studies When an animal succumbed during the test period, a gross autopsy * was performed. In those cases when postmortem autolysis was not ad vanced, representative tissues were taken and preserved in ten percent formalin solution for possible future histopathologic study. . After 3, 6, and 12 months of testing, five animals of each sex from eaeh group were sacrificed and subjected to complete gross pathologic examinations. GBRN002179 LEXOLDMON002516 B l O T E S T JaionatvuM., $me. 7 Absolut* organ weights w*r* recorded and organ to body weight and organ to brain weight ratios computed. The following organs were included: liver, kidneys, spleen, gonads, heart and brain. These data were then subjected to statistical analysis. An Analysis of Variance was conducted first and significant effects disclosed by that treatment were further studied by 'T'-tests. Complete microscopic examinations were conducted upon the tissues and organs from all control and 100 ppm group rats sacrificed after 3, 6, or 12 months of testing. The following tissues and organs were included in the examinations: heart, trachea, lungs, liver, pancreas, . esophagus, stomach, small intestine (duodenum, jejunum and ileum), caecum, colon, spleen, lymph nodes, kidneys, urinary bladder, gonads, prostate gland, seminal vesicles, uterus, pituitary gland, adrenal glands, salivary glands, thyroid gland, parathyroid glands, skeletal muscle, sternum, bone, peripheral nerve, spinal cord and brain (cerebrum, . cerebellum and pons). The aforementioned tissues were prepared and stained with Hematoxylin*Sosin stain. After two years of feeding, all surviving animals were sacrificed and subjected to complete gross pathologic examination. The absolute weights of the liver, kidneys, spleen, gonads, heart and brain were recorded immediately after sacrifice. GBRN0021B0 LEXOLDMON002517 Sttituinial BIO-TEST Jnitunfntiti, Smc. 8 Microseople examinations were conducted upon tissues end organs from selected animals dying during the experiment and upon all animals from the final sacrifice. ' Tissues and organs examined were the same as those previously mentioned. . I. Tumor Incidence and Classification A tabulation of the incidence of tumor formation in each group was made at the conclusion of the investigation. In addition, tumor data for individual animals including location, weight, size end pathologic classification were recorded. . * GBRN002181 LEXOLDMON002518 3*ditii'U*L BIO T E S T g IV. Results # A. Body Weights and Weight Gains j' Tht malt and ftmala body weight data art asitmbltd in Table II. The data in this tablt also iaeludt tht 3, 12 and 24 month total wtight gains. There were no significant effects attributable to the ingestion of the compound. \ 6BRNQ02182 LEXOLDMON002519 S.tliiiuaL B IO -T E S T A LEXOLDMON002520 i TABLE II TEST MATERIAL; Aroclor 1242 Two-Year Chronic Oral Toxicity Study - Albino Rats Body Weight and Total Weight Gain Data Summary of Mean Values dietary Level of Aroclor 1242 (ppm) Sex Body Weight (grams) Week: 0 1 2 3 4 5 6 7 8 5 10 II 12 13 Control M 133 203 245 313 362 373 391 409 424 440 440 449 467 474 F 136 178 190 219 244 254 259 265 270 276 281 278 290 288 1 M . 133 205 254 329 367 377 397 417 432 451 462 481 493 508 F * 136 173 197 226 240 253 268 292 278 280 284 284 288 292 10 M 133 202 251 332 362 372 392 414 428 454 475 481 500 509 F 136 176 196 226 244 254 268 288 276 280 281 284 280 285 100 M 133 203 248 320 365 376 398 416 427 439 453 467 478 487 F 136 173 194 225 251 264 272 290 274 275 279 285 283 286 90-Day Total Weight Gain (erams/rat) 341 152 375 156 376 149 354 150 G) CO D Zo o IS) oo C4 LEXOLDMON002521 tietary Level of Aroclor 1242 (ppm) Sex Control M F 1M F 10 M F 100 M F 4 498 297 525 302 525 299 504 290 TABLE II continued TEST MATERIAL: Aroclor 1242 Two-Year Chronic Oral Toxicity Study - Albino Rats Body Weight and Total Weight Gain Data Summary of Mean Values* 56 Body Weight (grams) Month: 78 9 10 11 533 565 593 622 642 667 688 310 322 333 345 359 374 383 555 580 614 640 665 690 707 321 326 333 342 355 367 381 553 579 600 627 641 674 693 312 328 333 346 354 365 375 533 551 580 608 633 662 686 307 321 333 347 360 374 388 12 701 390 743 388 706 384 711 379 G) CO 7) aZ o Mt- CO 12-Month Total Weight Gain (grams/rat) 568 254 610 252 573 248 578 243 Si 31 0 1a 7* W 1T V 1 S3 1 * 190 )ietary Level of Aroclor 1242 ' (ppm) Sex Control M F 1M F 10 M F . 100 M F TABLE II continued TEST MATERIAL: Aroclor 1242 Two-Year Chronic Oral Toxicity Study - Albino Rats Body Weight and Total Weight Gain Data . 13 14 15 Summary of Mean Values Body Weight (grams) Month: 16 17 18 19 20 21 24-Month Total Weight Gain 22 23 24 (grams/rat) 728 746 759 768 769 767 760 758 739 726 687 642 426 444 466 481 500 515 533 547 551 550 564 551 509 415 767 785 805 800 804 810 800 804 802 800 808 759 428 443 479 468 500 514 523 531 535 538 53S 532 740 750 763 780 784 780 785 783 780 774 796 734 393 406 422 441 462 480 500 519 529 533 537 547 724 728 723 735 728 736 733 730 725 715 743 652. 428 447 463 467 472 484 481 484 485 490 487 485 626 396 601 411 519 349 m oX I D Cl CO 70 zo O Z o N o0K0K133 CO in % JttLtiliial BIO T E S T Je&MotaMU, 13 At B. Food Consumption The data obtained from the food consumption measurements e *. conducted during the first 12 months of feeding are summarized in Table Cl. These data revealed no significant difference between test , and control rats. The periodic checks conducted during the remainder of the investigation also revealed no outstanding differences between test and control animals. GBRN00218& LEXOLDMON002523 s 3 1 o i ai TABLE III TEST MATERIAL: Aroclor 1242 Two-Year Chronic Oral Toxicity Study - Albino Rats Food Consumption Data Summary of Mean Values Food Consumption letary Level of (grams/rat/seven days) Average Food - Aroclor 1242 Week: Consumption (ppm) Sex 1 2 3 4 5 6 7 8 9 10 11 12 13 (grams/rat/seven days! Control .1 M 94 160 175 163 137 137 225 197 204 188 191 194 196 F 73 140 144 107 104 133 208 154 165 151 146 150 151 M 129 154 165 201 120 191 206 210 232 185 188 189 190 F 91 109 120 164 110 166 124 137 172 140 145 148 145 174 140 167 136 10 M 113 132 142 201 120 193 183 184 184 192 196 191 193 F 96 114 147 131 110 149 102 124 166 144 143 138 144 171 13t 100 M 117 149 185 230 161 172 199 172 227 192 186 190 190 F 89 118 129 189 98 114 142 135 180 145 142 139 140 182 135 m oX I Cl til D 70 z O Z o0K3 01 o N 00 vl etary Level of Aroclor 1242 (ppm) Sex 4 Control M 196 F 148 .1 M 180 F 152 10 M 184 F 139 100 M 179 F 163 TABLE III continued TEST MATERIAL: Aroclor 1242 Two-Year Chronic Oral Toxicity Study - Albino Rata Food Consumption Data Summary of Mean Values Food Consumption (grams/rat/seven days) ' Month: 5 6 7 8 9 10 11 12 189 168 147 163 184 179 170 187 154 136 121 138 152 160 141 127 181 170 189 190 189 196 192 208 159 . HI 154 150 148 143 145 159 164 168 197 193 188 191 186 177 147 136 151 144 145 138 142 130 192 189 200 196 186 184 187 167 141 160 148 145 144 147 146 145 Average Food Consumption (grams/rat/seven days) 176 142 188 150 183 141 187 149 *' ID O in LEXOLDMON002525 CmD 30 Z o o N 00 00 I. BtO*TS ST Jnc. C. Mortality and Reactions *. * A frequency distribution of natural deaths occurring during the investigation appears in Table IV. . No untoward behavioral reactions were noted among any of the animals employed in the investigation. SBRN0021B9 I 0B I T E ST Je&fnafaMct, Sue. LEXOLDMON002527 Dietary Level (ppm) Se* Control M F 1M F 10 M F 100 M F TABLE IV TEST MATERIAL: Aroclor 1242 Two-Year Chronic Oral Toxicity Study - Albino Rats Mortality Data Frequency Distribution of Deaths Frequency Distribution of Deaths Months: 1-3 4-6 7-9 10-12 13-15 16-18 19-21 000 2 1 7 6 000 1 3 5 7 20 1 1 3 3 7 1 00 1 3 2 4 000 2 1 7 5 01 1 2 0 2 5 000 3 3 6 7 0 10 1 2 4 8 22-24 9 3 8 5 8 5 10 9 Total Dead Number Tested* 25/35 19/35 25/35 16/35 23/35 16/35 29/35 25/35 * Does not include the five animals of each sex from every group sacrificed for interim pathologic studies. G> DO ZO Z a o N o a B1 O T E S T Jr>ia*a(<md, fmc. 18 D. Hematologic and Clinical Blood Chemistry Studies Mean male and female hematologic and elinical blood ehemistry /I data are summarized in Tablet V through DC. ` ' Values for all parameters investigated were within the normal range for the albino rat. No significant differences between test and control values were observed. GBRND02191 LEXOLDMON002528 fruluiltial BIO -TEST LEXOLDMON002529 Dietary Level (ppm) _ Sex Control- M F 3 14.0 9.1 M 15.6 100 F 15.6 TABLE V TEST MATERIAL: Aroclor 1242 Two-Year Chronic Oral Toxicity Study - Albino Rata Hematologic Data Summary of Mean Values Total Leukocyte Count (thousanda/mm^) Month: . 6 9 12 18 15.4 10. 1 11. 1 9.9 24 11.2 Erythnocyte Count (milliona/mm^) ' Month: 36 9 12 18 8. 1 8. 2 8.7 8.8 7.6 9.4 6.7 7.6 8.8 7.6 7.5 7.7 7.3 7.8 7.7 24 6.5 6.8 10.4 9.0 9.7 7.7 ` 12.5 7.8 9.4 6.2 9.3 6.4 7.7 8.0 8.0 7.6 7.4 7.6 7.6 7.1 7.9 7.0 7.7 7.2 r a oo 3J Z o M * *0 N It Dietary Level (ppm) Control 100 Sex 3 M 17.1 F 16.9 TABLE VI TEST MATERIAL: Aroclor 1242 Two-Year Chronic Oral Toxicity Study - Albino Rata Hematologic Data Summary of Mean Values Hemoglobin Concentration (g/100 ml) Month: 69 12 18 17.7 15.7 17.6 16. 1 17.4 14.I 16.7 16.4 24 13.6 14.6 Hematocrit Value 36 (%) Month: 9 12 18 51 49 48 50 41 50 47 43 46 42 O m in 24 35 38 M 16.8 16.9 14.2 15.4 15.6 14.6 F 15.8 16. 1 13.6 15.7 15.5 14.8 50 48 43 44 41 37 46 48 41 41 40 37 LEXOLDMON002530 tn ca x zo o N- NO 0 w ft V 1531*019 Dietary Level (ppm) Control Sex 3 M 82.0 F 83.0 TABLE VII TEST MATERIAL: Aroclor 1242 Two-Year Chronic Oral Toxicity Study - Albino Rats . Hematologic Data Summary of Mean Values 6 86.6 86.6 Differential Leukocyte Count (Number of Cells per Hundred) Lymphocytes Neutrophils Month: Month; 9 12 IB 24 36 9 12 18 80.4 78.8 79.0 65.4 16.0 11.4 18.6 20.6 20.0 86.8 89.0 70.2 61.4 15.4 11.6 11.8 10.0 29.2 24 32.2 36.0 M 89.6 84.4 . 79.8 87.0 66.0 58.4 9.6 15.2 18.8 13.2 33.0 38.8 100 F 91.4 86.0 82.8 88.4 75.6 65.2 8.4 13.6 17.2 11.2 23.0 33.6 m X oID tn DO X z o O oN z ooNcnO >0 . GO IM Dietary Level (ppm) Control Sex 3 M 0.6 F 0.6 TABLE VII continued * TEST MATERIAL: Aroclor 1242 Two-Year Chronic Oral Toxicity Study - Albino Rats Hematologic Data Summary of Mean Values m v* Differential Leukocyte Count (Number of Cells per Hundred) Monocytes Eosinophils Month: Month: 69 12 18 24 3 6 9 12 r r18 . 24 0.0 0.0 0.4 0.2 1.2 1.4 2.0 1.0 0.2 0.8 1.6 0.0 0.0 0.0 0.2 1.0 1.0 1.8 1.4 0.2 0.6 1.6 M 0.2 0.0 0.0 0.4 0.0 0.8 0.6 0.4 1.4 1.4 1.0 2.0 100 F 0.0 0.0 0.0 0.2 0.0 0.2 .0.2 0.4 0.0 0.2 1.4 1.0 0 m UJ oX ZJ z I- o Do ro O * z 0 cn o o NO cn CO NO INsi >7- i Dietary Level (ppm) Control Sex M . P M 100 F TABLE VII continued TEST MATERIAL: Aroclor 1242 Two-Year Chronic Oral Toxicity Study - Albino Rata Hematologic Data Summary of Mean Values 1 Differential Leukocyte Count (Number of Cells per Hundred) Basophils Month* 3 6 9 12 _ 18 24 0.0 0.0 0.0 0.0 ` 0.0 0.0 . .0.0 0.0 00 0.0 0.0 0.0 0.0 0.0 0.0 0.0 0.0 0.0 0.0 0.0 . 0.0 0,0 0.0 0.0 LEXOLDMON002533 G) CO JO z tv o o M -0 0* B IO -T E S T LEXOLDMON002534 TABLE VIII TEST MATERIAL: Arodor 1242 Two-Year Chronic Oral Toxicity Study - Albino Rats Clinical Blood Chemistry Data Summary of Mean Values Dietary Level <PPm> Sex Serum Glutamic-Pyruvic Transaminase Activity (Dade Units) Month: 3 6 9 12 Control M 38 F 33 48 45 39 . 38 45 42 18 31 32 24 36 30 Blood Urea Nitrogen Concentration (mgs %) Month: 3 6 9 12 1 17 15 12 10 14 14 16 15 9 13 15 11 M 33 35 36 57 39 32 100 ' F 39 41 53 40 52 46 15 15 13 14 12 20 17 14 14 11 11 14 G) M 7J Zo a N o * vl r BIO-TEST LEXOLDMON002535 V, Dietary Level (ppm) Sex 3 M 128 Control F 130 M 121 100 F 125 TABLE IX TEST MATERIAL: Aroclor 1242 Two-Year Chronic Oral Toxicity Study - Albino Rata Clinical Blood Chemistry Data Summary of Mean Values Fasted Blood Glucose Concentration (mgs %) Month: 6 9 12 18 123 89 88 138 24 99 Serum Alkaline Phosphatase Activity (King-Armstrong Units) Month: 3 6 9 12 18 24 28.6 24.7 21.5 20.3 16.2 22.3 118 115 92 134 109 18.9 17.8 10.6 11.9 16.8 20.2 123 129 145 125 115 118 124 121 135 116 26.4 27.6 23.2 20.3 17.4 9.6 25.8 11.7 16.7 11.6 e 13.2 14.2 0) ta 7} zo Nu o NM) O CO * f. BIO`TEST Jaia*afiiai, 9ma. 26 E. Urine Analyses Mean male and female urine analyses data are summarized in Tables X through XII. No differences were noted between the urine from control and test animals at the intervals of examination. 2r GBRND02199 LEXOLDMON002536 TABLE X TEST MATERIAL: Aroclor 1242 Two-Year Chronic Oral Toxicity Study - Albino Rats Urine Analyses Data Summary of Mean Values v ip m Dietary Level <PP*n> Control 100 Glucose Month: Sex 3 6 9 12 18 24 M n n n n nn F n n n n nn M n .n n n n n F n n n n nn Albumin Month: 3 6 9 12 18 24 Sr nn t. t 42 43 n n n n t 42 n n t t 41* 44 n n t t t 43 Keys n = negative t = trace; less than 30 mg/100 ml urine I * 30 to 100 mg/100 ml urine 42 = 100 to 300 mg/100 ml urine G) 43 s 300 to 500 mg/ 100 ml urine 00 Z 44' = more than 500 mg/100 ml urine z a to to a o t N-J LEXOLDMON002537 LEXOLDMON002538 TABLE XI TEST MATERIAL: Aroclor 1242 Two-Year Chronic Oral Toxicity Study - Albino Rata Urine Analyses Data Summary of Mean Values Dietary Level (PP") . Control Microscopic Elements Month: Sex 3 6 9 12 18 24 M N N N N N 41 F NNNNt t pH ' Month: 3 6 9 12 7 7 6. 7 8878 M N N N N Nt 77 78 100 F N N N N Nt 7767 Key: N= Normal t = trace; leas than 5 per low power field 4 1 s 5 to 10 per low power field 4-2 = 10 to 15 per low power field 43 s more than 15 per low power field ci 00 7J z o o to to o 18 24 76 66 6 6* 66 * $ V is a i*o i9 Dietary Level (PPm) ......... Control 100 TABLE XII TEST MATERIAL: Aroclor 1242 Two-Year Chronic Oral Toxicity Study - Albino Rata Urine Analyses Data Summary of Mean Values Specific Gravity Month: Sex 3 6 9 12 18 M 1.029 1.022 1.033 1.027 1.042 F 1.020 1.019 1.025 1.024 , 1.032 M 1.021 1.028 1.032 1.024 1.043 F 1.022 1.019 1.029 1.029 1.027 24 1.051 1.039 1.030 1.038 LEXOLDMON002539 G) DJ 30 Z Is* vO o o M K> IS) u Smiitikial BIO-TEST Jalmamfuitt, 3me. ?; 30 F. Pathologic Studies 1. Hire*-Month Sacrifice j- a. Groaa Pathologic Finding '` Gross pathologic findings among tsst animals were not significantly different from those noted in control animals. b. Organ Weight and Ratio Data The mean organ weight and ratio data collected at the three-month sacrifice are presented in Tables XIII through XVin. ' Statistically significant differences are designated by asterisks following the test group value. Organ weights, organ to body weight and organ to brain weight ratios disclosed several randomly occurring intergroup differences. The lack of any consistent dose related response and the absence of any deleterious histopathologic change confirm that these differences were not related to the ingestion of Arodor 1242. GBRN002203 LEXOLDMON002540 LEXOLDMON002541 Dietary Level . of Aroclor 1242 (ppm) Control 1 ' 10 100 Q CO X Z o N N O TABLE XIII TEST MATERIAL: Aroclor 1242 Two-Year Chronic Oral Toxicity Study - Albino Rats Organ Weight and Ratio Data Three-Month Sacrifice . Summary of Mean Values . Organ: Liver * , * Organ Weight (g) Males Females - Organ/Body Weight Ratio (g/100 g) Males Females 21.4 13.0 4.13 4.16 22.3 12.4 7 4.31 3.92 23.3 14.4 4.41 4.31 25.5 14.0 4.80 4.39 Organ/Brain Weight Ratio (g/g) Males Females 10.3 6.82 10.6 6.59 11.9 7.93 15.1 7.65 $ r > c I II i ft %  Dietary Level of Aroclor 1242 (ppm) Control 1 ` 10 100 TABLE XIV TEST MATERIAL: Aroclor 1242 Two-Year Chronic Oral Toxicity Study - Albino Rats Organ Weight and Ratio Data Three-Month Sacrifice Summary of Mean Values - Organ: Kidneys Organ Weight (g) Males Females 4.03 2.49 4.06 2.46 4.14 2.75 4.24 2.61 Organ/Body Weight Ratio (g/100 g) . Males Females 0.782 0.802 0.784 0.772 0.786 0.827 0.795 0.817 * . Organ/Brain Weight Ratio (g/g) Males Females 1.95 1.31 1.93 1.30 2.11 1.52 2.47 1.42 GBRN002205 o0K04^13 ' Dietary Level of Aroclor 1242 (ppm) Control 1 10 100 CD m 73 zo o N M O Q- TABLE XV TEST MATERIALS Aroclor 1242 Two-Year Chronic Oral Toxicity Study - Albino Rata Organ Weight and Ratio Data Three-Month Sacrifice Summary of Mean Values - Organ: Spleen Organ Weight (g) Males Females 0.766 0.578 0.768 0.544 0.756 0.596 0.814 0.528 Organ/Body Weight Ratio (g/100 g) Males . Females 0.150 0.184 0.148 0.171 0.143 0.179 0.154 0.166 Organ/Brain Weight Ratio (g/g) Males Females 0.371 0.302 0.364 0.287 0.385 . 0.328 0.468 0.288 ' Si a* iU ti*. li ' U - I w * TABLE XVI TEST MATERIALS Aroclor 1242 Two-Year Chronic Oral Toxicity Study - Albino Rats Organ Weight and Ratio Data Three-Month Sacrifice . ' Summary of Mean Values Organ: Gonads Dietary Level . of Aroclor 1242 (ppm) _ Control Organ Weight (g) Males Females 9 3.60 0.114 1 3.51 0.143* 10 3.50 0.112 100 3.49 0.112 Organ/Body Weight Ratio (g/100 g) Males Females 0.698 0.681 0.666 0.0370 0.0452 0.0336 0.656 0.0356 Organ/Brain Weight Ratio (g/g) Males Females 1.74 1.66 1.78 2.06 0.0599 0.0758 0.0616 0.0619 * Statistically significant difference at the 95 percent confidence level* LEXOLDMON002544 m w x za a N M o si Dietary Level of Aroclor 1242 (ppm) Control 1 10 100 TABLE XVII TEST MATERIAL: Aroclor 1242 Two-Year Chronic Oral Toxicity Study - Albino Rats Organ Weight and Ratio Data Three-Month Sacrifice ' ' Summary of Mean Values ' Organ: Heart ' Organ Weight (g) Males Females 1.59 1.05 1.58 1.02 1.55 1.10 1.61 1.05 Organ/Body Weight Ratio (g/100 g) Males Females 0.307 0.339 0.307 0.320 0.295 0.331 0.302 0.330 Organ/Brain Weight Ratio (g/g) Males Females 0.767 0.551 0.752 0.540 0.788. 0.943 0.608 0.573 LEXOLDMON002545 ttno a za a N N a ' oo LEXOLDMON002546 . Dietary Level of Aroclor 1242 (ppm) Control 1 10 100 TABLE XVIII TEST MATERIAL! Aroclor 1242 Two-Year Chronic Oral Toxicity Study - Albino Rats , Organ Weight and Ratio Data Three-Month Sacrifice Summary of Mean Values - Organ: Brain . Organ Weight (g) Males Females Organ/Body Weight Ratio (g/100 g) Males Females Total Body Weights of Sacrificed Rats (g) Males Females 2.07 1.91 0.402 0.616 518 314 2.12 1.97 1.82 1.89 1.81 1.83 0.410 0.375 0.345 0.597 0.545 0.576 520 318 527 334 534 319 ' Gto) 7} zo o M M O 0 c c r i tii i t f t i* c./ w/.-*/ B 1 O T E S T Jaiia/niM, Sue. J. 37 e. Histopathologic Finding! Histopathologic examination of tissues and organs taken from all animals from both the control and 100 ppm groups was conducted. Tables XDC and XX list all histopathologic changes noted. All of the lesions noted in the microscopic examination of tissues were those of spontaneous disease and are not unusual for the albino rat. The most frequent findings were lesions in the trachea and lungs, indicating chronic murine pneumonia. These occurred in the control as well as the rats fed Aroelor 1242. 6BRN002210 LEXOLDMON002547 B I O T E S T JaiviabtiU, Ate. 38 4; table XXX TEST MATERIAL: Areeler 1242 Two-Year Chronic Oral Toxicity Study - Albino Rats Histopathologic Changes Three-Month Sacrifice Group: Control ' Number of . Animals Organ Examined Findings 5 Males Trachea Lung Urinary Bladder Tracheitis Chronic respiratory disease Hyperplasia 5 Females Lung Chronic respiratory disease Average Incidence Grade 1 1.0 1 r.o 3 1.0 1 1.0 All other tissues and organs were normal histologically. Grading System . 0.5 * minimal 1.0 s slight 2.0 s mild 3.0* moderate 4.0 * severe 5.0 s extreme BBRND02211 LEXOLDMON002548 BI 0 * T S T Jo&oaoIoaiu, Sue. 39 JP, TABLE XX TEST MATERIAL: Arodor 1242 Two-Year Chronic Oral Toxicity Study - Albino Rats Histopathologic Changes Three-Month Sacrifice Group: 100 ppm Number of Animals Organ Examined Findings 5 Males Trachea Tracheitis 5 Females Lung Chronic respiratory disease Focal interstitial pneumonia Average Incidence Grade 2 1.0 2 . 1 1.0 1.0 All other tissues and organs were normal histologically. Grading System 0.5 s minimal 1.0,s slight 2.0 s mild 3.0 s moderate 4.0 s severe 5.0 s extreme ` 6BRN002212 LEXOLDMON002549 BIO T E S T Jabn\a(y\iu, Sue. SJ 40 2. Six-Month Sacrifice . a. Gross Pathologic Finding t No outstanding diffcraneas wars noted between test and control animals. ' b. Organ Weight and Organ to Body and * Organ to Brain Weight Ratio Data The results of the statistical anlayses conducted on ab solute organ weights, organ to body weight and organ to brain weight ratios are summarized in Tables XXI through XXVI. Organ weights, organ to body weight and organ to brain a weight ratios disclosed several randomly occurring intergroup differences. The lack of any consistent dose related response and die absence of any deleterious histopathologic change confirm that these differences were not related to the ingestion of Arodor 1242. 6BRN002213 LEXOLDMON002550 rwys/* 1 S 3 1 * 0 19 F W T - 'l * % ' Dietary Level of Aroclor 1242 (ppm) Control 1 10 100 . TABLE XXI TEST MATERIAL} Aroclor 1242 Two-Year Chronic Oral Toxicity Study - Albino Rata Organ Weight and Ratio Data Six-Month Sacrifice * Summary of Mean Values '. Organ Weight (g) Males Females Organ: Liver Organ/Body Weight Ratio (g/100 g) Males Females Organ/Brain Weight Ratio ' (g/g) Males Females 22.9 13.1 3.74 3.77 11.7 6.71 13.8** 9.98* 2.85** 3.15 6.86** 5.76 22.3 13.2 4.08 4.23 11.0 6.95 22.0 11.7 4.58* 3.70 10.8 % 5.94- * Statistically significant difference at the 95 percent confidence level. * Statistically significant difference at the 99 percent confidence level. GBRN002214 o0K3 0O1i b S u iu ll'ia l B IO - T E S T JaiMatvutt. Sme. LEXOLDMON002552 ' Dietary Level of Aroclor 1242 ipuml Control 1 10 100 TABLE XXII TEST MATERIALS Aroclor 1242 Two-Year Chronic Oral Toxicity Study - Albino Rats Organ Weight and Ratio Data Six-Month Sacrifice ' Summary of Mean Values Organ: Kidneys . Organ Weight (g) Males Females ' 4.04 2.79 Organ/Body Weight Ratio (g/100 g) Males Females 0.664 0.806 Organ/Brain Weight Ratio (g/g) Males Females 2.06 1.43 3.51 2.44* 0.728 , 0.774 1.75 1.41 3.75 2.49* 0.686 0.790 1.86 1.31 3.54 2.33* 0.730 0.757 1.74 1.18 * Statistically significant difference at the 95 percent confidence level. tn 00 7zo1 o Nro cn N fc 1 S 3 1 * 180 w/ * ' Dietary Level of Aroclor 1242 (ppm) Control 1 10 ' 100 TABLE XXIII TEST MATERIALS Aroclor 1242 Two-Year Chronic Oral Toxicity Study - Albino Rats Organ Weight and Ratio Data Six-Month Sacrifice Summary of Mean Values . . Organ: Spleen ' t Organ Weight (g) Males Females 0.752 0.754 0.684 0.542* 0.796 0.622 0.584 0.488* Organ/Body Weight Ratio (g/100 gf Males Females 0.122 0.196 0.154 0.172 0.142 0.199 0.120 0.159 Organ/Byain Weight Ratio (g/g) Males Females 0.384 0.350 0.375 0.313 0.394 0.327 0.288 0.248 LEXOLDMON002553 * Statistically significant difference at the 95 percent confidence level. cn . 03 30 Zo o N NI-- O .  % Dietary Level of Aroclor 1242 (ppm) Control 1 10 100 TABLE XXIV TEST MATERIALS Aroclor 1242 Two-Year Chronic Oral Toxicity Study - Albino Rats . Organ Weight and Ratio Data Six-Month Sacrifice Summary of Mean Valuea ' Organ: Gonads Organ Weight (8) Malea Femalea 3.55 0.0960 3.44 0.0810 3.55 0.106 3.35 0.0772 Organ/Body Weight Ratio (g/100 g) Males Femalea 0.593 0.0279 0.716 0.0253 0.652 0.697 0.0335 0.0251 Organ/Brain Weight Ratio (g/g! Malea Femalea. 1.81 0.0492 1.71 0.0468 1.76 0.0558 1.65 0.0392 LEXOLDMON002554 a 3) z o N M Vi TP 3.idttitUaL B IO T EST LEXOLDMON002555 TABLE XXV TEST MATERIAL; Aroclor 1242 Two-Year Chronic Ora! Toxicity Study - Albino Rats Organ Weight and Ratio Data Six-Month Sacrifice Summary of Mean Values ' Organ: Heart Dietary Level of Organ Weight Aroclor 1242 (g) (ppm) Males Females Control ` 1.70 1.05 1 1.49 1.03 10 1.46 1.06 100 1.42 0.970 Organ/Body Weight Ratio (g/100 g) Males Females 0.282 0.302 0.309 0.325 0.267 0.335 0.293 0.314 Organ/Brain Weight Ratio (g/g) Males Females 0.867 0.538 0.741 0.595 0.722 0.558 0.700 0.492 0 u z o M Ni- 00 t LEXOLDMON002556 * % , ' Dietary Level of Aroclor 1242 (ppm) Control 1 ` 10 100 . TABLE XXVI TEST MATERIAL: Aroclor 1242 Two-Year Chronic Oral Toxicity Study - Albino Rats _ Organ Weight and Ratio Data ' Six-Month Sacrifice ' ' Summary of Mean Values . Organ: Brain , i * Organ Weight (g) Males Females Organ/Body Weight Ratio (g/100 g) Males Females Final Body Weights of Sacrificed Rats (g) Males Females 1.96 1.95 0.320 0.560 . 613 348 2.01 1.73 0.415 0.546 484 317 2.02 1.90 0.369 0.597 548 318 2.03 1.97 0.416 0.635 488 310 tn cd a zo o N N*-* >0 *c im q a v f v r 1 s 3 1 C 19 O' x. Km JrJuihiat BI 0 T E S T /rfflWnnf. Sue. 47 e. Histopathologic Findings Histopathologic examination of tissues and organa taken I from all animals from both tho control and 100 ppm groups was eondueted. Tables XXVII &nd XXVDZ list all histopathologic changes noted. All of the lesions noted in the mieroseopie examination of tissues were those of spontaneous disease and are not unusual for the albino rat. The most frequent findings were lesions in the traehea and lungs, indicating chronic murine pneumonia. These occurred in the control as well as the rats fed Aroclor 1242. * GBRN002220 LEXOLDMON002557 tr/..-1-W BIO-TEST 3*c. 46 Jts TABLE XXVH TEST MATERIAL: Aroclor 1242 i / Two-Year Chronic Oral Toxicity Study - Albino Rats Histopathologic Changes Six-Month Sacrifice Group: Control Number of Animals Organ Examined Findings Average Incidence Grade 5 Males Trdchea Lung Liver Skeletal Muscle Traeheitis Focal tracheitis Focal pneumonitis Hyperemia Focal pericholangitis Focal inflammation 2 1.5 2 1.0 1 0.5 2 l.'O l 1.0 1 1.0 5 Females Trachea Lung Liver Kidney Focal tracheitis Hyperemia Hyperemia Pericholangitis Focal pneumonitis I. 2 1 1 1 1.0 2.5 1.0 0.5 1.0 All other tissues and organs were normal histologically. Grading System 0.5 * minimal 1.0* slight 2.0* mild 3.0 * moderate 4.0 * severe 5.0* extreme . " ' GBRN002221 LEXOLDMON002558 3miuiUkd BIO-TEST JtiUffumi, jU 49 > TABLE XXVIH TEST MATERIAL: Aroelor 1242 Two-Year Chronic Oral Toxicity Study - Albino Rats Histopathologic Changes Six-Month Sacrifice Croup: 100 ppm Number of Animals Organ Examined Findings Average Incidence Grade 5 Males Trachea Lung 5 Females Trachea Lung Tracheitis Focal tracheitis Focal pneumonitis Hyperemia Focal tracheitis Focal pneumonitis Hyperemia 2 2 3 2. 1 1 1. 1.0 0.5 1.5m 1.0 . 1.0 0.5 2.0 All other tissues and organs were normal histologically. Grading System 0.5 * minimal 1.0 s slight 2.0: mild 3.0 * moderate 4.0 * severe 5.0 extreme 6BRN002222 LEXOLDMON002559 SrAulual B I O T E S T JaU*a(<\\iU, Sac. so 3 Twelve-Month Sacrifice j' a. Groee Pathologic Finding ' Gross pathologic findings among tost animals were not significantly different from those r*oted in eontrol animals. b. Organ Weight and Ratio Data The mean organ weight and ratio data eolleeted at the twelve-month sacrifice are presented in Tables XXIX through XXXIV, Statistically significant differences are designated by asterisks following the test group value. 1 Organ weights, organ to body weight and organ.to brain weight ratios disclosed several randomly occurring intergroup differences. The lack of any consistent dose related response and the absence of any deleterious histopathologic change confirm that these differences were not related to the ingestion of Aroelor 1242. BBRN002223 LEXOLDMON002560 Dietary Level (ppm) Control 1 10 100 TABLE XXIX TEST MATERIAL: Arocior 1242 Two-Year Chronic Oral Toxicity Study i Albino Rats Twelve-Month Sacrifice Organ Weight and Ratio Data Summary of Mean Values Organ: Liver Organ Weight (g) Males Females Organ/Body Weight Ratio (g/100 g) Males Females - 22.1 15.5 3.79 3.52 22.7 22.4 13.7 14.4 3.45 3.48 3.33 3.44 26.3 14.4 3.78 3.59 Organ/Brain Weight Ratio (g/g) Males Females 10.8 7.72 10.4 10.6 12.4 7.05 7. 39 7.16 fuc. I: S T n O LEXOLDMON002561 0to) 7J z o o M N .N c Ul I 4 LEXOLDMON002562 . * Dietary Level (ppm) Control 1 10 100 . TABLE XXX TEST MATERIAL: Aroclor 1242 Two-Year Chronic Oral Toxicity Study - Albino Rats , Twelve-Month Sacrifice Organ Weight and Ratio Data Summary of Mean Values Organ: Kidneys ' Organ Weight (g) Males Females 4.04 3.19 4.31 2.93 4.27 3.24 4.98* 3.01 Organ/Body Weight Ratio (g/100 g) Males Females Organ/Brain Weight Ratio . (g/g) Males Females 0.692 0.656 0. 738 0. 735 1.97 1.97 1.58 1.51 0.662 0.716 0. 779 0. 745 ' 2.02 2.33 1.66 1.50 * Statistically significant difference at the 95 percent confidence level. cn co ;o za o NJ IS) NCJl ti' C3 O - m S' S S' s v* Ul N 0S tu ln lh -tu l D I T E S T Jj& >H lfoU rS , SnC. LEXOLDMON002563 Dietary Level (ppm) Control 1 10 100 TABLE XXXI TEST MATERIAL: Aroclor 1242 Two-Year Chronic Oral Toxicity Study - Albino Rats Twelve-Month Sacrifice Organ Weight and Ratio Data Summary of Mean Values . ' Organ: Spleen Organ Weight (g) Males Females Organ/Body Weight Ratio (g/100 g) Males Females Organ/Brain Weight Ratio (g/g) Males Females 0. 788 1.000* 0.868 0. 968 0.796 0.600 0. 664 0. 570 0.133 0. 152 0.136 0. 138 0. 183 0. 153 0. 160 0.145 0.380 0.458 0.412 0.454 0. 396 0. 307 0. 341 ' 0.285 4 Statistically significant difference at the 95 percent confidence level. G) CO 2) zo a N N N O' S ,,Jn ih icl Bl 0 T EST mf\. Ul-i. Joe. TABLE XXXII tEST MATERIAL: Aroclor 1242 Two-Year Chronic Oral Toxicity Study i Albino Rats Twelve-Month Sacrifice Organ Weight and Ratio Data Summary of Mean Values Organ: Gonads Dietary Level (ppm) Organ Weight (g) Males Females Organ/Body Weight Ratio (g/100 g) MalesFemales Organ/Brain Weight Ratio (g/g) Males Females Control 1 10 100 3.46 3.47 3.00 3.67* 0. 116 0.0938 0.141 0. 122 0. 596 0. 529 0.457 0. 531 0.0275 0.0239 0.0332 0.0305 * Statistically significant difference at the 95 percent confidence level. 1.70 1.59 1.40 1.72 0.0574 0.0483 * 0.0719 0.0608 t LEXOLDMON002564 G) ' m 71 2 IS) IS) ... ' ' v * 'fM U 'jr'ity T 1 S 3 i * 0 1o r v w Dietary Level (ppm) Control 1 10 100 TABLE XXXIII TEST MATERIAL; Aroclor 1242 Two-Year Chronic Oral Toxicity Study - Albino Rats Twelve-Month Sacrifice Organ Weight and Ratio Data Summary of Mean Values . ' Organ: Heart Organ Weight Organ/Body Weight Ratio (g) (g/100 g) MalesFemalesMalesFemales Organ/Brain Weight Ratio ' (g/g) Males Females 1.71 1.69 1.68 1.87 1.23 1.18 1.29 1.19 0.293 0. 258 0.263 0.268 0.286 0.298 0.312 0.298 0. 835 0.776 0.799 0. 878 0.609 0.610 0.663 0. 591 LEXOLDMON002565 CD CD JO z itnn a aM IS) M CO -a/y 'r ":7 y /y $ g X - 0 1 fl 7'Vyr".r ''/i Dietary Level (ppm) Control 1 10 100 TABLE XXXIV TEST MATERIAL: Aroclor 1242 Two-Year Chronic Oral Toxicity Study - Albino Rats Twelve-Month Sacrifice Organ Weight and Ratio Data Summary of Mean Values Organ: Brain Organ Weight (g) Males Females 2.04 2.02 2.19 1.95 2.11 1.95 2.14 2.00 Organ/Body Weight Ratio (g/100 g) Males Females 0.351 0.474 0.334 0.516 0. 329 0.473 0.310 0. 508 Final Body Weight of Sacrificed Animals (grams) Males Females 584 439 660 431 642 425 698* * i/ *o> ? 9S LEXOLDMON002566 * Statistically significant difference at the 95 percent confidence level. cn CO z o o N N N>0 BIO T E S T JakiafMiM, Sue 57 r e. Histopathologic rinding Histopathologic examination of tissues taken from each rat sacrificed from the control and 100 ppm groups after twelve months of testing was conducted. Tables XXXV and XXXVI list all histopathologic changes noted. All of the lesions noted in the microscopic examination were those of spontaneous disease and cannot be related to the ingestion of Aroclor 1242. GBRND02230 LEXOLDMON002567 SnittlLtial B I O T E S T Jai&abrtu, Sue. 58 TABLE XXXV TEST MATERIAL: Aroelor 1242 Two-Year Chronic Oral Toxicity Study - Albino Rats Histopathologic Changes Twelve-Month Sacrifice Croup: Control Number of Animals Organ Examined Findings Incidence 5 Males Trachea Lung Urinary Bladder Tracheitis Chronic respiratory disease Calculus 1 2 1 5 Females Trachea Lung Colon Tracheitis Chronic respiratory disease Parasites 1- 11 Average Grade 1.0 J.O l.Q 1.0 1.0 1.0 All other tissues and organs were normal histologically. Grad ing Svstem . 0.5= minimal 1.0 = slight 2.0 = mild 3.0 = moderate 4.0 =severe 5.0 * extreme GBRN002231 LEXOLDMON002568 6BRN002232 LEXOLDMON002569 jndtaUial B I O T E S T 2ak>*e 3*c. 3t 59 TABLE XXXVI TEST MATERIAL: Aroclor 1242 Two-Year Chronic Oral Toxicity Study - Albino Rats Histopathologic Changes Twelve-Month Sacrifice Croup: 100 ppm Number of Organ Animals Examined Findinss ` Average Incidence Grade 5 Males Trachea Lung Liver Pancreas Kidney Pituitary Adrenal Tracheitis Chronic respiratory disease Congestion Focal atrophy Focal lymphoid infiltration Chromophobe hyperplasia Nodular hyperplasia Hematoeyst - 5 Females Trachea Lung Tracheitis Chronic respiratory disease 1 4 1 1 1 1 1 1. 1 1 1.0 1.0 1.0 1.0 1.0 1.0 1.0 1.0 1.0 1.0 All other tissues and organs were normal histologically. Grading System 0. 5 s minimal 1.0 s slight 2. 0 * mild 3.0 * moderate 4. 0 s severe 5.0 * extreme. GBRN002233 LEXOLDMON002570 r.j..itAimt BIO T E S T /iWmix, Sttc. 60 JLi - 4. Final Sacrifice a. Gross Pathologic Findings Grets pathologic findings among test animals were not significantly different from those noted in control animals. * b. Organ Weight and Ratio Data The mean organ weight and ratio data collected at the final sacrifice are presented in Tables XXXVU through XLXL Statistically significant differences are designated by asterisks following the test group value. The absolute liver weight and liver to body or brain weight ratios were significantly evaluated in female rats fed 100 ppm Arpclor 1242. Statistical evaluations of other organ weights, organ to body weight and organ .to brain weight ratios disclosed several randomly occurring intergroup dif ferences. The lack of any consistent dose related response indicates that these differences were not related to the ingestion of Arodor 1242. 6BRN002234 LEXOLDMON002571 y rv o jm v jv r x s 3 - O ! 9i stary Level (ppm) Control 1 10 100 TABLE XXXVll TEST MATERIAL: Arodot 1242 Two-Year Chronic Oral Toxicity Study - Albino Rata Organ Weight and Ratio Data Summary of Mean Values Final Sacrifice ' Organ Weight Males (g* Females Organ: Liver Organ/Body Weight Ratio (g/100 g) Males Females 22.0 21.9 22.3 25.6 16.3 15.7 17.1 22.4+* 3.47 2.93 3. 18 3.95 3.05 3.00 3.19 4.82** Organ/Brain Weight Ratio (g/g) Males Females 10.10 9.97 * 10.20 11.90 8.42 8.03 8.50 11.60** * Statistically significant difference at the 99 percent confidence level. 1 r r 19 j LEXOLDMON002572 Cl CO 71 zo o N M W Ul 1t w f o S 3 1 - 1S T^-V 'T'S0 etary Level (ppm) Control 1 10 100 TABLE XXXVIII TEST MATERIAL: Aroclor 1242 Two-Year Chronic Oral Toxicity Study - Albino Rata Organ Weight and Ratio Data Summary of Mean Values Final Sacrifice Organ Weight (g)' Males Females 5.57 3.48 6.13 3.45 Organ: Kidneys Organ/Body Weight Ratio (g/100 g) Males Females 0.877 0.646 0.820 0.670 Organ/Brain Weight Ratio (g/g) Males Females 2.57 1.79 2.78 1. 76 5.63 5.44 3.43 3.43 0.816 0. 835 0.644 0.725 * 2.56 2.52 1.71 1.79 LEXOLDMON002573 CD CO X O' z IV o o M M <A 0* U is a i-o ia m etary Level (ppm) Control 1 10 100 .fc TABLE XXXIX TEST MATERIAL: Aroclor 1242 /, Two-Year Chronic Oral Toxicity Study - Albino Rats Organ Weight and Ratio Data Summary of Mean Values Final Sacrifice Organ: Spleen ' v Organ Weight Males (g* Females Organ/Body Weight Ratio (g/100 g) Males Females Organ/Brain Weight Ratio (g/g> Males Females 1.15 1.26 1.08 1.07 0.96 0.81 0. 82 0.65 0.182 0.169 0.158 0.165 0.181 0.158 0.153 ` 0. 140 0.520 0.572 * 0.495 0.499 0.492 0.145 0.409 0.339 i- cn om X CD 73 z I- o Da IS) O z oo NJ <NA) Kcn3  . TABLE XL TEST MATERIAL: Arocloi 1242 Two-Year Chronic Oral Toxicity Study - Albino Rata L oj o Organ Weight and Ratio Data Summary of Mean Values Final Sacrifice Organ: Gonads ' '. ^ - Organ Weight Organ/Body Weight Ratio Organ/Brain Weight Ratio etary Level (gfr (g/100 g) (g/g) (ppm)MalesFemalesMalesFemalesMalesFemales Control 2.52 0. 123 0.397 0.0222 I. 15 0.0628 1 3. 20 0. 102 0.424 0.0205 1.46 0.0523 10 3.00 100 3.31 0. 126 0. 129 0.437 0.514 0.0237 0.0278 * 1.40 1.55 ~~-- 0.0625 0.0671 LEXOLDMON002575 G) BJ X O' Z a a N N w 00 tl t- 'r 1 S 3 1 -O I8 6 itary Level (ppm) Control 1 10 100 TABLE XLI TEST MATERIAL: Aroclor 1242 Two-Year Chronic Oral Toxicity Study - Albino Rats Organ Weight and Ratio Data Summary of Mean Values Final Sacrifice Organ Weight Males <B> Females Organ: Heart Organ/Body Weight Ratio (g/100 g) Males Females ' ' v Organ/Brain Weight Ratio <g/e) Males Females 1.87 2.30* 2.08* . 2. 19* ` 1.54 1.51 1.59 1.41 0.294 0.307 0.303 0.335 0.288 0.292 0. 298 0. 303 0.860 1.040** * 0.959* 1.010** 0.795 0.770 0.788 0.741 Statistically significant difference at the 95 percent confidence level. * Statistically significant difference at the 99 percent confidence level. LEXOLDMON002576 Cl Oi/>' a Z Z a a w w w b >o Dietary Level (ppm) Control 1 10 100 TABLE XLII TEST MATERIAL: Aroclor 1242 Two-Year Chronic Oral Toxicity Study - Albino Rats Organ Weight and Ratio Data Summary of Mean Values , Final Sacrifice ' Organ: Brain . Organ Weight (g) Males Females Organ/Body Weight Ratio (g/lOOg) Males Female Final Body Weight of Sacrificed Animals (grams) Males Females . 2. 18 1.95 0.342 0.362 642 551 2.20 1.96 0.294 0.388 759 532 2. 18 2.01 0. 313 0. 379 734 547 2.14 1.91 0. 330 0.415 652 485 O m v* l r LEXOLDMON002577 Cl CO Xz a O' O' a N NJ E a ll jfttdttiiAiei BIO-TEST Shc. Si 67 c. Histopathologic Findings Histopathologic examination of tissuIies and organs taken from all animals sacrificed after 24 months on test was conducted. Tables XLIH through XLVI list all histopathologic changes noted. Table XLVU contains the results of the histopathologic examination of the urinary bladders. Significant liver injury was found in animals fed 100 pprr. Aroclor 1242 (T-HI).. The compound associated lesions consisted of vacuolar change, focal hypertrophy and focal hyperplasia. In addition, there were lesions of inflammation, necrosis, fibrosis and minor degeneration in this group which, although seen in the controls and lower test groups, were more severe and frequent in the T-IH group. - The vacuolar change was not seen in the control animals but was observed occasionally in liver from T-I (1 ppm) and T-II (10 ppm) animals. The vacuolar change was observed frequently in the T-UI animals. This lesion is morphologically indicative of fatty degeneration. Formalin- frozen sections of livers from representative animals which displayed vacuolar changes were stained with Oil Red O to reveal the presence of fat. The vacuolar lesion in the cytoplasm of these cells was positively identified as fat. '* The hypertrophic change found in the liver was focal and often limited to the central lobular area where groups of cells were swollen to two or three times their normal size with clear pink homogeneous cytoplasm. GBRN002241 LEXOLDMON002578 3*duikial B1 O T E S T JaianaivUu, Sttc. 68 The hyperplasia wu associated with the same eells and appeared to be an extension of the hypertrophic lesion. The hyperplastic cells were also usually hypertrophie. The most severe examples of hyperplasia appeared as nodular growths with limited compression of the surrounding normal hepatic tissue. The minor lesions of degeneration, hepatitis, ductule cell proliferation, necrosis and focal lymphoid infiltration seen in the control animals and the T-I and T-II groups are lesions of spontaneous disease and are not related to the Aroelor 1242. This level of liver disease is not unusual in old animals. * Hyperplasia of the transitional epithelium was present in the urinary bladder of animals from the control group and from each of . the test groups. This lesion was usually associated with cystitis. All of the other lesions in the other tissues found in these animals are related to spontaneous disease and they are not unusual for rats of this age. Donovan . Cordon, D. V. M., Ph. D. Diplomats, American College of Veterinary Pathologists GBRN002242 LEXOLDMON002579 LEXOLDMON002580 Number of Animals 11 Males Cl CO 71 z f-l o c 04 table xliii TEST MATERIAL: Aroclor 1242 Two-Year Chronic Oral Toxicity Study - Albino Rats Histopathologic Changes Final Sacrifice Group: Control Organ Examined Heart Trachea Lung Liver .. . Stomach Spleen Kidney Testes . Prostate Adrenal Gland Brain Eye Findings Chronic focal myocarditis Tracheitis Chronic respiratory disease Focal degeneration Ductile hyperplasia Chronic gastritis Hemosiderosis Chronic nephritis Testicular degeneration Periarteritis . Inflammation Telangiectasis ' Nodular hyperplasia Focal fatty change Focal encephalitis Inflammation ' Incidence 3 3 9 1 2 1 3 8 2 2 1 1 1 1 2 Average Grade 1.0 1.0 1.0 1.0 1.0 1.0 1.0 1.0 1.0 1.0 1.0 1.0 1.0 1.0 1.0 1.0 h `i f ' W F T . 1 S 3 1 0 1 8 TcrvP " 7 >' t 'prrvvjBwyof i s g x 0 19 T ^ V 'T ^ S TABLE XLHI continued TEST MATERIAL: Aroclor 1242 Two-Year Chronic Oral Toxicity Study - Albino Rats Histopathologic Changes Final Sacrifice Croup: Control Number of Average AnimalsOrgan ExaminedFindingsIncidenceGrade 14 Females Heart Trachea Lung Liver Stomach Colon Spleen Uterus Kidney Ovary 7J . Z o o ----------------------------------M N Chronic focal myocarditis Tracheitis Chronic respiratory disease Focal lymphoid infiltration Ductile hyperplasia Focal hepatitis Non-lipid vacuolar change Chronic gastritis Acanthosis - squamous epithelium Parasites Hemosiderosis Metritis Chronic nephritis Focal lymphoid infiltration Cyst , `7 9 13 3 2 I 2 - 3 5 I 4 3 6 I 1 2.0 1.0 1.0 1.0 1.0 1.0 0.5 1.0 1.0 1.0 1.0 2.0 1.0 1.0 1.0 j o LEXOLDMON002581 LEXOLDMON002582 Number of Animals 14 Females TABLE XLIII continued TEST MATERIAL: Aroclor 1242 Two-Year Chronic Oral Toxicity Study - Albino Rats Histopathologic Changes Final Sacrifice Group: Control' Organ Examined Adrenal Gland Salivary Gland Findings Telangiectasis Nodular hyperplasia . Chronic fibrosis and atrophy t Incidence 9. 4 1 All other tissues and organs were normal histologically. 0.5 = minimal 1.0 = slight Grading System 2.0 = mild 3.0 s moderate 4.0 = severe 5.0 = extreme cn W 73 Z w M -E cn Average Grade 1.0 1.0 1.0 e* IL 'fvru q tn o jB j- x S 31 0 IQ LEXOLDMON002583 Number of Animals 13 Males CD tl) - ro ZO Q M N C o . t TABLE XLIV TEST MATERIAL: Aroclor 1242 Two-Year Chronic Oral Toxicity Study - Albino Rats Histopathologic Changes Final Sacrifice Group: 1 ppm < . Organ Examined Heart Trachea Lung Liver Stomach Spleen Kidney Testes Prostate Adrenal Gland Findings Chronic focal myocarditis Tracheitis Chronic respiratory disease . Focal lymphoid infiltration Cirrhosis Congestion Chronic gastritis and acanthosis Hemosiderosis Chronic nephritis Calcification Periarteritis Testicular degeneration ' Inflammation Telangiectasis Nodular hyperplasia ` - '* ' . Incidence 5 9 12 1 1 1 2 4 9 1 2 1 1 2 1 Average Grade 1.0 2.0 1.0 1.0 1.0 1.0 1.0 2.0 2.0 1.0 2.0 1.0 4.0 1.0 2.0 i-^4* U 1 S 3 * 0 1 fl T A F T 'SI \ -vug im y n c fv f 1 S 3 1 0 1 8 Number of Animals 14 Females . 0) DO 30 Z o o I'd C vj TABLE XLIV continued TEST MATERIAL: Aroclor 1242 Two>Year Chronic Oral Toxicity Study - Albino Rats Histopathologic Changes Final Sacrifice Group: 1 ppm . Organ Examined Heart Trachea Lung Liver Pancreas Stomach . Spleen Kidney Uterus Adrenal Gland Findings Chronci focal myocarditis Tracheitis Chronic respiratory disease Ductile hyperplasia Chronic focal pancreatitis Chronic gastritis Ulcerative gastritis Acanthosis Hemosiderosis Chronic nephritis Metritis Telangiectasis '' Incidence 6. 7 13 3 2 2 1 2 B 6. I 10 Average Grade 1.0 i.O 1.0 1.0 1.0 1.0 1.0 1.0 2.0 1.0 ' 1.0 1.0 All other tissues and organs were normal histologically. 0.5 = minimal 1.0 = slight Grading System 2. 0 = mild 3.0 = moderate 4. 0 = severe 5. 0 = extreme cI LEXOLDMON002584 LEXOLDMON002585 Number of Animals 13 Males * 0 0. a CD TABLE XLV TEST MATERIAL: Aroclor 1242 Two-Year Chronic Oral Toxicity Study - Albino Rats Histopathologic Changes Final Sacrifice Group: 10 ppm Organ Examined Heart Trachea Lung Liver . Pancreas Stomach Spleen Kidney Testes Findings Chronic focal myocarditis Tracheitis Chronic respiratory disease Focal hypertrophy and hyperplasia Hypertrophy Vacuolar change (fatty) Ductile hyperplasia Chronic focal pancreatits Acanthosis Inflammation, ulceration and necrosis Hemosiderosis ' Chronic nephritis Testicular degeneration Periarteritis '' Incidence ty 7 9 1 1 2 1 3 6 1 7 10 2 3 fr 1 S= 1* C !s Average Grade 1.0 1.0 2.0 1.0 1.0 I/O 2.0 1.0 1.0 1.0 1.0 2.0 3.0 3.0 V* LEXOLDMON002586 TABLE XLV continued TEST MATERIAL: Aroclor 1242 Two-Year Chronic Oral Toxicity Study - Albino Rats Histopathologic Changes ' Number of Animals Organ Examined Final Sacrifice Group: 10 ppm* . Findings 13 Males 13 Females q S P o r-j . JZ o Prostate Adrenal Gland Heart Trachea Lung Tongue Stomach Spleen Lymph Node Kidney Uterus Adrenal Gland Inflammation Telangiectasis Medullary hyperplasia Nodular hyperplasia Chronic focal myocarditis Tracheitis Chronic respiratory disease Periarteritis Chronic gastritis and acanthosis Ulceration Hemosiderosis - Edema Chronic nephritis Metritis ` Telangiectasis Nodular hyperplasia . All other tissues and organs were normal histologically. .' 0. f* - minimal Grading System 2.0 - mild 4.0 = severe Incidence 2 4 1 2 1 5 9 1 5 1 5 * ^ 2 ** J ' Average Grade ^ f * S ^ 3.0 1.0 1.0 1.0 1.0 1.0 1.0 2.0 1.0 1*0 2.0 ** ,* 1* u w '*9fitn-not*iyr i r s i . a i s LEXOLDMON002587 Number of Animals 6 Males ' CD m za a N N ui a TABLE XLVI TEST MATERIAL: Aroclor 1242 Two-Year Chronic Oral Toxicity Study - Albino Rats Histopathologic Changes Final Sacrifice Group: 100 ppm' Organ Examined Heart Trachea Lung Liver Pancreas Testes Stomach Spleen Lymph Node Kidney Findings Chronic focal myocarditis Tracheitis Chronic respiratory disease Focal degeneration Focal hypertrophy Hypertrophy Vacuolar change (fatty) Periarteritis . Periarteritis . Chronic gastritis and acanthosis Periarteritis Hemosiderosis ' Periarteritis Chronic nephritis Incidence 3. 3 6 1 1 1 3 1 3 1. 1 1 1 4 I O m UI - fe g Average Grade 1.0 2.0 1.0 1.0 1.0 i.-o 1.0 3.0 2.0 1.0 2.0 1.0 3.0 2.0 ft -j O' a LEXOLDMON002588 Number of Animals 6 Males 14 Females G) a 3 z o N is) Ul TABLE XLVI continued TEST MATERIAL: Aroclor 1242 Two-Year Chronic Oral Toxicity Study - Albino Rats Histopathologic Changes Final Sacrifice Group: 100 ppm' . ( Average Organ ExaminedFindingsIncidenceGrade Prostate Adrenal Gland Salivary Gland Eye . . Inflammation Focal fatty change Focal chronic inflammation Inflammation 1 1 1 1 3.0 1.0 1.0 1.0 Heart Trachea Lung Liver Chronic focal myocarditis Tracheitis Chronic respiratory disease Focal degeneration Focal hyperplasia Focal hypertrophy Hypertrophy Nodular hyperplasia Focal cholangiqhcpatitis 4 .8 6 3 2 2 3 1 1 1.0 1.0 1.0 1.0 1.0 1.0 2.0 1.0 1.0 -*J1 L Stic. BI O T EST LEXOLDMON002589 TABLE XLVI continued TEST MATERIAL: Aroclor 1242 Two-Year Chronic Oral Toxicity Study - Albino Rats Histopathologic Changes Final Sacrifice Group: 100 ppm Number of Animals Organ Examined Findings 14 Females , Ul z o N N Ul N Liver (continued) Pancreas Stomach . Spleen Lymph Node Kidney Uterus Adrenal Gland Focal hepatitis Hyperplasia Vacuolar change (fatty) Chronic focal pancreatitis Chronic gastritis Acanthosis Ulcerative gastritis Ulcer Hemosiderosis Congestion Chronic nephritis Metritis Telangiectasis Nodular hyperplasia Acanthosis 1 All other tissues and organs were normal histologically. Incidence 1 1 11 1 2 2 *1 1 4 1 7 2 8 4 1 0. 5 = minimal 1.0 = slight Grading System Z. 0 = mild 3.0 = moderate 4. 0 = severe 5.0 = extreme * ' Average Grade 1.0 3.0 1.0 1.0 1.0 1.0 1.0 1.0 2.0 1.0 1.0 1.0 1.0 1.0 1.0 w /r rmcimotreT I < 3 1 O 1f! .W s/w i BIO -TEST LEXOLDMON002590 TABLE XLVII TEST MATERIAL: Aroclor 1242 Two-Year Chronic Oral Toxicity Study - Albino Rata Histopathologic Changes of the Urinary Bladder Final Sacrifice Group C Sex M F - Number Examined 11 14 Findings* Proteinaceous plug (34) Focal epithelial hyperplasia (62) T-I (1 ppm) M 12 F 13 Proteinaceous plug (582) Diffuse epithelial hyperplasia associated with diffuse cystitis (566) Diffuse epithelial hyperplasia associated with diffuse cystitis (580) None T-11 (10 ppm) M 11 Diffuse epithelial hyperplasia associated . with diffuse cystitis (651) Diffuse epithelial hyperplasia associated with diffuse cystitis and a proteinaceous G) 0) F 13 plug (655) None Zo o T-I1I M6 Proteinaceous plug (744) - IS) M (100 ppm) Ul W F 13 Focal epithelial hyperplasia (767) ' Individual animal numbers arc shown in parentheses. Grading System 1.0 - minimal or trace 4.0 = severe 2. 0 = mild . 5.0 r extreme 3.0 = moderate Incidence 1 1 1 1 1 1 1 1 1 Average Grade . 1. m 2 1 - 3 1 2 1 Sitd^^iucl B I O - T E S T XaJt&aloAiti. Sue. 80 a: C. Detailed Description of Tumor Findings Tumor data for individual animals including location, weight and pathologic classification are presented in Table XLVIH through LI. None of these tumors could be related to the ingestion of Aroelor 1242 and are considered normal for a random population of rats this age. BBRN00225M LEXOLDMON002591 LEXOLDMON002592 t <Vnimal 'umbc r nd Sex 1-M 2-M 16 -F Location Abdomen Pancreas Abdomen 47-F Lymph node 48-F Abdomen 50-F Abdomen 52-F Abdomen cn 59-F CD Abdomen JO zp Adrenal gland 64-F N Abdomen M tn 66-F Ut . Abdomen TABLE XLVIII TEST MATERIAL: Aroclor 1242 Two-Year Chronic Oral Toxicity Study - Albino Rats Description of Tumor Findings Group: Control Weight (grams) 11.76 64.98 35.09 - 88.92 230.00 Size (cm) 8x1x2 5x2x2 2x2x1 2x2x3 s t 13 x 11 x 4 13x11x4 Classification Mammary fibroadenoma Ade nocar cinoma Mammary fibroadenoma Mammary fibroadenoma Reticulum cell sarcoma Mammary fibroadenoma Mammary fibroadenoma Mammary fibroadenoma Mammary fibroadenoma Phcochromocytoma Fibroadenoma Mammary adenoma Months on Test 24 24 24 24 24 7 24 24 24 24 tJr.tjov'yer 1 s31* 0 1a F W T f LEXOLDMON002593 Animal Numbe r and Sex 566-M 569-M 604-F f*09-F 611-F 613-F 615-F Cl GO 33 Zo o w IS) Ul 0 Location ' Abdomen Spleen Abdomen Abdomen Abdomen Ovary Abdomen Abdomen TABLE XL1X TEST MATERIAL! Arodor 1242 Two-Year Chronic Oral Toxicity Study - Albino Rata Description of Tumor Findings Group: 1 ppm Weight (grams) 15.00 53.50 35.00 - 335.00 Size (cm) - - 5x3x1 |. 5x3x1 Ixlxl 3x2x1 - 13 x 10 x 5 ' * Classification Adenocarcinoma Lymphosa rcoma Mammary fibroadenoma Fibroadenoma Fibroadenoma Fib roadenoma Granulosa cell tumor Fibroadenoma Mammary fibroadenoma Months on Test 24 22 24 24 24 24 i 23 .1 r Do N s31 o i ai LEXOLDMON002594 Animal Number and Sex 621-F 627-F 628-F 630-M 631 -F 634-F 635-F G) O 2J Zo a N N Ul Location Abdomen Pituitary Abdomen Abdomen Uterus Abdomen Abdomen Abdomen Pituitary TABLE XLIX continued 'TEST MATERIAL: Aroclor 1242 Two-Year Chronic Oral Toxicity Study - Albino Rats Description of1 Tumor Findings Group: 1 ppm Weight (grams) 18.00 - - 157.20 117.90 44.00 13.41 39-36 - Size (cm) 1x3x3 '- 6x3x3 9x6x4 7x6x2 3x2x1 - 6x5x3 6x5x4 - Classification Fibroadenoma Chromophobe adenoma Fibroadenoma Mammary fibroadenoma Mammary fibroadenoma Fibroma Fibroadenoma Fibroadenoma Fibroadenoma Chromophobe adenoma i-. i- ! xr C . " Months on Test 24 24 24 23 24 *-- 24 24 oo X* >4 LEXOLDMON002595 TABLE L TEST MATERIAL: Aroclor 1242 Two-Year Chronic Oral Toxicity Study - Albino Rats Description of Tumor Findings Group: 10 ppm Animal Number and Sex Location Weight (grams) Size (cm) Classification 640-M Abdomen 129.0 9x7x3 Fibroadenoma 646-M 662-M Pancreas Adrenal gland Pituitary Abdomen - 280.0 * - - Islet cell adenoma Medullary tumor Chromophobe adenoma Mammary fibroadenoma 687-F Pituitary - - Chromophobe adenoma 689-F Abdomen - - Mammary adenocarcinoma 690-F Pituitary - - Chromophobe adenoma 695-F 697-F 703- F CD CO VO Zo o Is) -- N U1 CO Abdomen Abdomen Abdomen Parathyroid gland 3.90 23. 15 175.0 - 3x3x2 7x6x3 8x7x5 - Mammary fibroadenoma . .Mammary fibroadenoma Mammary fibroadenoma Adenoma Months on Test 24 24 r 24 22 . 24 24 24 24 . 24 24 oo Va T 1 S3 1 OI a F W 'T'S M u te d BIO -TEST A LEXOLDMON002596 Animal Number and Sex 707-F 708-F 711-F 712-F TABLE L continued TEST MATERIAL! Arcelor 1242 Two-Year Chronic Oral Toxicity Study - Albino Rats Description of Tumor Findings Group: 10 ppm Location Abdomen Abdomen Abdomen Subcutaneous, abdominal Weight (grams) 74.6 189.0 6. 96 155.0 Size (cm) 7x6x3 5x4x1 3x2x1 11x8x3 Classification Mammary fibroadenoma Mammary fibroadenoma Mammary fibroadenoma Fatty tissue fibroma Months on Test 24 24 24 ~ 24 G) CO 7} Z CUDt o o IS) IiSn) -o S- 7 1 3 1 O I 9 Animal Number and Sex 744-M 775-F 785-F 789-F 794-F TABLE LI TEST MATERIAL: Aroclor 1242 Two-Year Chronic Oral Toxicity Study - Albino Rats Description of Tumor Findings Group: 100 ppm Location Pancreas Ovary Pituitary Adrenal gland Abdomen Weight (grams) -' '- 260.0 Size (cm) 10 x 10 x 5 Classification Islet cell adenoma Granulosa cell tumor Chromophobe adenoma Medullary tumor . Mammary fibroadenoma Months on Test ' 24 24 24 24 23 LEXOLDMON002597 G) CO * Z a w O' N N O' o V V*