Document qkBmaZQxg1kVa0YaLJ05yqygx

PROJECT RErC'fiT FILS --------- SfuMWucd Bio - test jGjkmfou&b. Dnc. 1810 FRONTAGE ROAD NORTHBROOK. ILLINOIS 60062 REPORT TO MONSANTO COMgkip'. TWO-YEAR CHRONIC ORAL TOXICITY WITH AROCLOR 1260 . IN ALBINO RATS NOVEMBER 12,' 1971 .vy ' ' ' JSt IBT NO. B7298 . BBRN0023M9 LEXOLDMON002686 !-.d*dual B I O T E S T Ja&onaLvUt, jUc REPORT TO MONSANTO COMPANY TWO-YEAR CHRONIC ORAL TOXICITY WITH AROCLOR 1260 IN ALBINO RATS NOVEMBER 12, 1971 IBTNO. B7298 L Introduction At the request of Monsanto Company, a two-year chronic oral toxicity study was conducted using albino rats to determine the potential toxicity of Aroclor 1260, Lot No. AK-3. The following report presents the results of this investigation. 6BRN0D2350 LEXOLDMON002687 * 9-4--kud BI O T E S T JsJtMaitHiM, ime. 2 o IL Summary . A two-year chronic toxicity study was conducted using albino rats fed diets containing 1 (T-I), 10 (T-II), or 100 (T-III) ppm Arodor 1260. Food consumption and body weight gains were not altered at any level of Arodor 1260 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 1260. 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 9 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 1260. 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 * the rats from the T-IZI group. Histologic examination of the livers from the T-IQ group revealed several animals with vacuolar change. This lesion is morphdogically 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 Aroclor 1260. EBRN002351 I LEXOLDMON002688 S.uLsiuaL BI 0 T E S T Jaio*abi*i, !*&. 3 Hyperplasia of the urinary bladder was found in an animal from the control group but not in any of the test animals. ' 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 Smith, B. S. Assistant Toxieologist Rat Toxicity Report approved by: JLmhs 5. Plank Settlor Croup Leader Rat Toxicity Paul L. Wright, Ph. D. Section Head, Toxicology November 12, 1971 lamtsjn ' 6BRN002352 LEXOLDMON002689 B I O T E S T 2alo*ai&tiM, 2c. 4 XU. Procedure ' A. Experimental Animals ' The animal* employed in the test were Charles River strain* albino rats. Four hundred rats (200 males and 200 females) were selected for the experiment, ear-punched with the animal number assigned and housed individually in standard wire-bottomed steel rat cages. Each cage bore a color-coded card identifying the rat with re - speet to project number, dose level assignment, individual animal number and sex. B. Organization of Groups A structural outline of the experiment is given in Table L TABLE I . TEST MATERIAL: Aroclor 1260 . Two-Year Chronic Oral Toxicity Study - Albino Rats ' Outline of Experiment Croup Number of Animals Male Female Dietary Level (ppm) Control 50 50 None Administered T-I SO 50 1 T-II so 50 10 T-III 50 50 100 * Charles River Breeding Laboratories, North Wilmington, Mass. GBRN002353 LEXOLDMON002690 3 I O - 7 c 5 T 2a&o\ala*Ui, 3*o 5 C. Diets. Feeding and Food Consumption * . All diets were prepared in the central diet room of this laboratory. The basic ration from which all diets were constructed was a standard, pulverized stock rat ration*. The diet for any given test group was prepared by blending the calculated amount of Arodor 1260 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 Cains 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.__________ - _________ __ J E. Mortality and Reactions ` ;. 1- 1 Checks for mortality and abnormal behavioral reactions were .made daily throughout the investigation. : 7-!' F. Hematologic Studies and Urine Analyses Blood studies, including determinations of hemoglobin concentra tions, hemotocrit value, erythrocyte count and both total and differential * Purina Rat Chow, Ralston Purina Co., St, Louis, Mo. 6BRN002354 LEXOLDMON002691 BIO-T EST 2a&a*aian4Mi. /ml 6 O O leukocyte count*, were conducted upon five melee end five femeles from both the control end 100 ppm group*. Urine enelyaes for the preaence of glucoae, albumin, microcopic elementa, end determinationa of pH end apecific gravity were con ducted upon urine eamplea at the came time intervela end from the aeme animals ea thoae employed for the blood atudier. These studies were conducted after 3, 6, 9, 12, 18, end 24 months of feeding. G. Clinical Blood Chemistry Studies Determinations of blood urea nitrogen concentration (BUN), serum alkaline phosphatase activity (SAP), fasted blood glucose .concen- , tration and serum glutamic-pyruvic transaminase activity (SGPT) 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 each group were sacrificed and subjected to complete gross pathologic examinations. GBRN002355 LEXOLDMON002692 Q I 0 * T c S T IshwaioMti, Smc. 7 Absolute organ weights were recorded end orgen to body weight end orgen to brein weight retios computed. The following organs were included: liver, kidneys, spleen, gonads, heart end brein. These date were then subjected to statistical analysis. An Analysis of Variance was conducted first and significant effects disclosed by that treatment were farther 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-Eosin stain. ~' ' ` lr 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. GBRN00235& LEXOLDMON002693 B I 0 * T E S T Ja&MatarUat, 3*c. 8 Microscopic examinations were conducted upon tissues and 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. L 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 and pathologic classification were recorded. GBRN002357 LEXOLDMON002694 BIO-TEST J*c. 9 XV. Results A. Body Weights and Weight Gain* The male and female body weight data are assembled in Table II. The data in this table also include the 3. 12 and 24 month total weight gains. There were no significant effects due to ingestion of the compound GBRN002358 LEXOLDMON002695 oo TABLE II TEST MATERIAL: Aroclor 1260 Two-Year Chronic Oral Toxicity Study - Albino Rats Body Weight and Total Weight Gain Data Summary of Mean Values lietary Level of Aroclor 1260 (ppm) Sex Control M F Body Weight 90-Day (grams) Total Weight Week: Gain 0 1 2 3 4 5 6 7 8 9 10 11 12 13 (trams/rat) 133 203 245 313 362 373 391 409 424 440 440 449 467 474 136 178 190 219 244 254 259 265 270 276 281 278 290 288 341 152 1 M 133 192 250 322 361 374 394 416 428 448 450 474 479 490 357 F ' 136 167 189 218 241 252 256 261 268 273 277 281 290 288 152 e 10 M 133 204 245 317 368 382 400 417 436 448 461 467 475 481 348 F 136 174 190 217 242 254 260 263 268 274 281 279 285 288 152 100 M 133 208 247 319 363 375 394 425 437 451 460 479 486 500 367 F 136 173 188 222 240 253 258 262 265 267 270 275 275 280 144 mo oX 00 7i r~ z o Do N OW z 01 o >0 o K3 O) CD Dietary Level of Aroclor 1260 (PPm) Sex Control M F 1M F 10 M F 100 M F O I TABLE II continued * TEST MATERIAL: Aroclor 1260 Two-Year Chronic Oral Toxicity Study - Albino Rata Body Weight and Total Weight Gain Data Summary of Mean Values Body Weight (grams) Month: 4 5 6 7 8 9_ 10 11 498 533 565 593 622 642 667 688 297 310 322 333 345 359 374 383 516 547 578 600 628 643 668 688 298 307 314 321 333 340 353 367 496 526 551 581 606 633 660 685 291 306 314 331 340 358 370 381 522 555 580 607 633 650 `681 707 289 302 307 314 326 333 342 347 o 12-Month Total Weight Gain 12 (arams/rat) 701 568 390 254 699 * 379 566 243 709 576 388 252 717 584 363 227 LEXOLDMON002697 Q DJ 3 ZQ O M W 0O Dietary Level of Aroclor 1260 (ppm) Sex 'ontrol M F 1M F 10 M F 100 M F Oo TABLE II continued TEST MATERIAL: Aroclor 1260 Two-Year Chronic Oral Toxicity Study - Albino Rata Body Weight and Total Weight Gain Data 9 Summary of Mean Values 13 14 15 16 Body Weight (grama) Month: 17 18 19 20 21 22 24-Month Total Weight Gain 23 24 (g rama/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 i 721 740 760 768 776 774 762 753 733 718 715 654 390 427 466 433 445 476 481 493 514 530 484 525 509 415 521 385 728 745 776 761 768 780 774 761 735 715 683 645 416 434 482 449 473 508 519 530 536 542 536 584 512 . 448 746 760 772 775 774 769 760 750 733 714 711 641 380 386 417 414 435 453 471 481 500 507 485 537 508 401 LEXOLDMON002698 to 2 Z o o N W > B I O T E S T laLonatvUU, Stte. 13 B. Food Consumption The date obtained from the food consumption measurements conducted during the first 12 months of feeding are summarized in Table HI. 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. GBRN002362 LEXOLDMON002699 4* OvJ TABLE III TEST MATERIAL: Aroclor 1260 Two-Year Chronic Oral Toxicity Study - Albino Rate Food Consumption Data o * p i. i* , O) o m in Summary of Mean Values 1 Food Consumption ietary Level of (grams/rat/seven days) Average Food Aroclor 1260 Week: Consumption ppm) Sex 1 2 3 4 5 6 7 8 9 10 11 12 13 (fframs/rat/seven dayi Control 1 10 100 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 118 154 151 169 201 116 200 198 201 193 189 187 194 F 95 118 97 139 160 107 162 139 165 149 150 143 147 M 106 146 144 142 190 136 196 214 214 192 191 199 200 F 94 124 128 124 179 90 190 167 155 151 150 149 152 M 121 150 156 117 187 124 121 190 196 186 184 199 189 F 89 93 123 151 151 101 193 136 140 144 144 147 146 174 140 175 136 * 175 143 163 135 LEXOLDMON002700 tn gxj z o o NM O* M Oo ietary Level of Aroclor 1260 <ppTM> Sex Control M F 4 196 148 1 M ' 196 F 148 10 M 186 F 142 100 M 179 F 156 TABLE III continued TEST MATERIAL: Aroclor 1260 ' Two-Year Chronic Oral Toxicity Study - Albino Rate Food Consumption Data Summary of Mean Values Food Consumption (grams/rat/seven days) Average Food Month: Consumption 5 6 7 8 9 10 11 12 (grams/rat/seven days) 189 168 147 163 184 179 170 187 154 136 121 138 152 160 141 127 176 142 200 189 192 179 181 182 172 184 163 141 163 160 153 157 143 132 191 188 193 197 197 168 164 196 138 145 144 144 151 136 139 141 * 186 151 186 142 . 170 180 188 186 ' 166 181 188 180 127 147 144 134 132 162 149 139 180 143 CP O m in t LEXOLDMON002701 a o a z o o N W c BIO-TEST JaltMaittniM, St 16 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. 4 BBRN002365 LEXOLDMON002702 3 10 T EST LEXOLDMON002703 Dietary Level (ppm) Sex Control #' 1 M F M F. 10 M F 100 . M F . TABLE IV TEST MATERIAL: Aroclor 1260 Two-Year Chronic Oral Toxicity Study - Albino Rata 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 00 1 1 4 7 5 000 2 3 3 6 1 .1 0 2 4 7 8 000 3 2 4 5 1 00 2 2 8 6 0 22 0 3 5 7 22-24 9 3 8 5. 6 3 9 4 O K ir> Total Dead Number Tested* 25/35 19/35 26/35 19/35 29/35 17/35 29/35 23/35 * Does not include the five animals of each sex from every group sacrificed for interim pathologic studies. 01 CO 7) z o o N W (h 0* I B l O T E S T JLaAatal&uu. 2*c. 18 D. Hematologic and Clinical Blood Chemistry Studio Mean male and female hematologie and clinical blood ehemistry data are summarized in Tables 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. . GBRND02367 LEXOLDMON002704 SmLiinial B IO T E S T 2*!* LEXOLDMON002705 Oo Dietary Level (ppm) Control Sex 3 M 14.0 F 9.1 TABLE V TEST MATERIALS Arodor 1260 Two-Year Chronic Oral Toxicity Study - Albino Rata Hematologic Data Summary of Mean Values Total Leukocyte Count (thousands/mm^) Month: 6 9 12 18 24 3 Erythrocyte Count (millions/mm^) ' Month: 6 9 12 18 15.4 9.4 10. 1 6.7 11. 1 7.6 9.9 11.2 8.8 7.6 8. 1 8.2 8.7 8.8 7.6 7.5 7.7 7.3 7.8 7.7 24 6.5 6.8 M 10.8 13.1 7.9 12.8 8.6 8.4 100 F 13.2 8.2 7.9 6.5 7.8 7.4 7.5 8.1 8.0 7.6 8.0 7.6 7.3 7.5 7. 3 7.5 7.4 6.4 0) GO 7} Z oo M x\ Wo> 00 IS 3 1 * 0 1 8 "F v m Dietary Level (ppm) Sex 3 M 17.1 Control F 16.9 M 16^ 1 100 F 16.3 O TABLE VI * TEST MATERIAL! Aroclor 1260 Two-Year Chronic Oral Toxicity Study - Albino Rata Hematologic Data Summary of Mean Values Hemoglobin Concentration (g/100 ml) Month: 6 9 12 18 24 3 Hematocrit Value <%> Month: 6 9 12 17.7 17.4 15.7 14. 1 17.6 16.7 16. 1 13.6 16.4 14.6 51 49 48 50 50 47 43 46 17.2" 17.0 14.0 13.7 15.3 15.6 15.9 14.5 15.3 12.9 0 49 47 43 43 48 47 41 44 o 18 24 41 35 42 38 41 38 e 39 32 LEXOLDMON002706 GI to 3 Zo o N W 0* 'O i ro* 3*dtuUial b I U I 6 4 I JLatuHaioAUi. 'Jmc. Ooo Dietary Level (ppm) Sex 3 Control M 82.0 F 83.0 . TABLE VII TEST MATERIAL: Arodor 1260 Two-Year Chronic Oral Toxicity Study Albino Rata Hematologic Data Summary of Mean Valuea Differential Leukocyte Count (Number of Celia per Hundred) Lymphocytea Neutrophlla Month: Month: 6 9 12 18 24 3 6 9 12 18 24 86.6 80.4 78.8 79.0 65.4 16.0 11.4 18.6 20.6 20.0 32.2 86.6 86.8 89.0 70.2 61.4 15.4 11.6 11.8 10.0 29.2 36.0 M 85.8 85.4 83.4 72.4 73.8 66.6 100 F 92.0 89.6 78.8 82.2 80.6 65.6 12.6 13.8 15.8 22.6 24.6 3I.*6 7.6 10.0 19.4 17.0 17.4 34.2 ci LEXOLDMON002707 0 CO 50 Z o o M W O 1$31*0 IB V W T f Oo Dietary Level (ppm) Control Sex 3 M 0.6 F 0.6 TABLE VII continued TEST MATERIAL: Arodor 1260 Two-Year Chronic Oral Toxicity Study - Albino Rats Hematologic Data Summary of Mean Values Differential Leukocyte Count (Number of Cells per Hundred) Monocytes Eosinophils Month: Month: 6 9 12 18 24 3 6 9 12 0.0 0.0 0.4 0.2 1.2 1.4 2.0 1.0 0.2 0.0 0.0 0.0 0.2 1.0 1.0 1.8 1.4 0.2 18 0.8 0.6 24 1.6 1.6 M 0.0 0.0 0.0 0.0 0.4 0.8 100 F 0.0 0.0 0.0 0.0 0.4 0.2 1.4 0.8 0.8 1.0 1.2 1.0* 0.4 0.4 0.8 0.8 1.6 0.0 LEXOLDMON002708 GI W 3 Z o hi oN N WNJ T IS 3 1 *0 1 9 / * W 1T I O TABLE VII continued TEST MATERIAL: Arodor 1260 Two-Year Chronic Oral Toxicity Study - Albino Rats Hematologic Data Summary of Mean Values Differential Leukocyte Count (Number of Cells per Hundred) Dietary Basophils Level Month: (ppm)Sex369121824 M 0.0 Control F 0.0 0.0 0.0 0.0 0.0 0.0 0.0 0.0 0.0 4 M 0.2 . 0.0 0.0 0.0 0.0 100 F 0.0 0.0 0.0 0.0 0.0 o ' 0.0 0.0 0.0 0.0 LEXOLDMON002709 O CO 73 z NU o o Is) sWj IS) Dietary Level Ippm) Control Sex 3 M 38 F 33 M 33 100 F 29 e , TABLE VIII TEST MATERIAL: Aroclor 1260 Two-Year Chronic Oral Toxicity Study - Albino Rata Clinical Blood Chemistry Data Summary of Mean Values Serum Glutamic-Pyruvic Transaminase Activity (Dade Units) Month: 6 9 12 18 i 24 3 6 Blood Urea Nitrogen Concentration (mgs %) Month: 9 12 18 24 48 45 45 42 36 17 15 12 10 14 15 39 38 42 32 30 14 16 15 9 13 11 39 42 43 31 36 37 50 40 32 33 14 15 17 16 16 15 . 15 15 14 13 12 14 LEXOLDMON002710 CD a 7z3 o o IS} M Nl (A vu/r prncm ttrrT | ( 3 1 *0 1 (1 Dietary Level (ppm) Sex 3 M 128 Control F 130 1 100 M 118 F 117 o . TABLE IX TEST MATERIAL: Aroclor 1260 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 24 Serum Alkaline Phosphatase . Activity (King-Armstrong Units) Month: 3 6 9 12 18 24 123 89 88 138 99 28.6 24.7 21.5 20.3 16.2 22.3 118 115 92 134 109 118 116 135 146 98 116 115 138 146 94 18.9 37.8 12.0 17.8 21.8 12. 1 10.6 21.9 7.6 11.9 23.9 11.7 16.8 11.9 7.8 20.2 16.1 12.4 CD tu om X X z o I D a w w O sc Z o o K3 iNn S*tukiaL B I O I fc 6 I JLa&anala/uei. Jne. 26 E. Urine Analyses Mean male and female urine analyses data are summarized in Tables X through XU. Determinations for glucose concentration were negative for all rats at every interval of examination. No' differences were noted between the urine from control and test animals at die intervals of examination. GBRN002375 LEXOLDMON002712 BIO -TEST LEXOLDMON002713 Dietary Level IPPTM) Sex 3 Control Mn Fn Mn 100 Fn TABLE X TEST MATERIAL: Arodor 1260 Two-Year Chronic Oral Toxicity Study - Albino Rate Urine Analyses Data Summary of Mean Values Glucose Month: 6 9 12 nnn nnn 18 24 nn nn Albumin Month: 3 6 9 12 18 24 n n t t 42 43 n n n n t 42 n n n nn n n n nn n t t 1 41 43 n n . n n 4 1 44 Key: n = negative , t trace; less than 30 mg/100 ml urine + 1 s 30 to 100 mg/100 ml urine ffl +2 * 100 to 300 mg/100 ml urine 3) 43 s 300 to 500 mg/100 ml urine o +4 = more than 500 mg/100 ml urine a M w vl O' . t N-4 B IO 'T E S T BBRN0Q2377 O Dietary Level (ppm) Sex 3 Control MN FN MN 100 FN o TABLE XI ' TEST MATERIAL! Aroclor 1260 Two-Year Chronic Oral Toxicity Study - Albino Rata Urine Analyses Data Summary of Mean Values o Microscopic Elements Month: 6 9 12 18 NNNN NNNt 24 +1 t pH Month: 3 6 9 12 18 24 776776 8 8 7 8 6. 6 N N N Nt N N N tt 776766 78 6 7 6 6 Key: . Ns Normal t s trace: less than 5 per low power field 1 s 5 to 10 per low power field +2 s 10 to IS per low power field 4 3s more than 15 per low power field .' t o K3 IM 00 O Dietary Level (ppm> Control 100 o Sex M F M F TABLE XII TEST MATERIAL: Aroclor 1260 Two-Year Chronic Oral Toxicity Study - Albino Rata Urine Analyses Data Summary of Mean Values 3 1.029 1.020 1.021 . 1.016 6 . 1.022 1.019 1.025 1.023 Specific Gravity Month: 9 12 1.033 1.027 1.025 1.024 1.031 1.035 ' 1.030 1.029 18 1.042 1.032 I 1.043 1.028 o 24 1.051 1.039 1.039 * 1.045 LEXOLDMON002715 G) GO 7} Zo o IM wN| 00 B I O * T E S T Ja&vtatoAU*, 2*e. 30 . P. Pathologic Studies ` . 1. Three-Month Sacrifice n- Grose Pathologic Findings No outstanding differences were noted between test and control rats upon gross pathological examination. Organ Weight and Organ to Body and Organ to Brain Weight Ratio Data Hie results of the statistical analyses conducted on absolute organ weights, organ to body weight and organ to brain weight ratios are summarized in Tables XHX through XVIZL . Significant differences between a test group and the control group are designated by asterisks following the test values. 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 Aroclor 1260. . 6BRN002379 LEXOLDMON002716 LEXOLDMON002717 O i Dietary Level of Aroclor 1260 (ppm) Control 1 10 100 oo TABLE XIII TEST MATERIAL} Aroclor 1260 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 21.4 13.0 20.4 13.2 24.0* 12.2 29.5** 14.5 Organ/Body Weight Ratio (g/100 g) Males Females Organ/Brain Weight Ratio (g/g) Males Females 4.13 4.16 10.3 6.82 3.90 4.59 9.98 6.86 4.48 3.61 ` 11.8 6.38 5.73*a 4.58 14.4** 7.72 a Statistically significant difference at the 99 percent confidence level. 0) DO 71 Z o o M W 00 O .. '` I O VI f r O Dietary Level of Aroclor 1260 (ppm) Control 1 10 100 o TABLE xnr TEST MATERIAL; Aroclor 1260 Two-Year Chronic Oral Toxicity Study - Albino Rato Organ Weight and Ratio Data Three-Month Sacrifice Summary of Mean Values Organ: Kidneys ' o Organ Weight (g) Males Females 4.03 2.49 4.37 2.62 4.00 2.61 4.00 2.52 Organ/Body Weight Ratio (g/100 g) Males Females 0.782 0.802 0.838 0.911 0.747 0.782 0.779 0.793 Organ/Brain Weight Ratio (g/g) Males Females 1.95 1.31 2.14 1.36 1.96 1.37 1.96 1.35 I < n fa LEXOLDMON002718 Cl to 31 t I Z Q a NJ w 09 % Dietary Level of Aroclor 1260 (ppm) Control 1 10 100 OO TABLE XV TEST MATERIAL! Aroclor 1260 Two-Year Chronic Oral Toxicity Study - Albino Rats - Organ Weight and Ratio Data . . Three-Month Sacrifice Summary of Mean Values Organ: Spleen . . . Organ Weight (g) Males Females 0.766 0.578 0.846 0.516 0.838 0.632 0.718 0.556 , Organ/Body Weight Ratio (g/100 g) Males Females 0.150 0.184 0.161 0.180 0.156 0.189 0.140 0.177 Organ/Brain Weight Ratio (g/g) Males Females 0.371 0.302 . 0.412 0.269 0.411 0.331 0.352 0.297 6BRN002382 i o ftidiM nai o i wr LEXOLDMON002720 G Dietary Level of Aroclor 1260 (PPm* Control 1 10 100 O TABLE XVI TEST MATERIAL* Aroclor 1260 Two-Year Chronic Oral Toxicity Study - Albino Rata Organ Weight and Ratio Data Three-Month Sacrifice Summary of Mean Valuea Organ: Gonada , . O .. Organ Weight (g) Maiea Femalea 3.60 0.114 3.67 0.128 3.83 0.121 3.71 0.138 Organ/Body Weight Ratio (g/100 g) Maiea Femalea 0.698 0.0370 0.704 0.0450 0.715 0.0368 0.725 0.0429 Organ/Brain Weight Ratio (g/g) Maiea Femalea 1.74 0.0599 1.80 0.0666 1.89 0.0636 1.81 0.0728 tn u xz a a N w 03 W LEXOLDMON002721 0 Dietary Level of Aroclor 1260 (ppm) Control 1 10 100 w TABLE XVII TEST MATERIAL: Aroclor 1260 Two-Year Chronic Oral Toxicity Study - Albino Rata Organ Weight and Ratio Data Three-Month Sacrifice Summary of Mean Values Organ: Heart . Organ Weight (g) Males Females 1.59 1.05 1.57 1.01 1.58 1.04 1.52 0.946 Organ/Body Weight Ratio (g/100 g) Males Females 0.307 0.300 0.339 0.353 0.296 0.311 0.298 0.297 Organ/Brain Weight Ratio (g/g) Males Females 0.767 0.551 0.765 0.526 0.781 0.743 0.546 0.505 CD 00 73 Za wa w so C C p a ; v O Dietary Level . of Arodor 1260 <PPn) ... Control 1 10 100 oQ TABLE XVIII TEST MATERIAL: Arodor 1260 Two-Year Chronic Oral Toxicity Study - Albino Rata Organ Weight and Ratio Data . Three-Month Sacrifice Summary of Mean Values Organ: Brain . Organ Weight (g) Males Females 2.07 1.91 2.05 1.92 2.04 1.91 2.05 1.89 , Organ/Body Weight Ratio (g/100 g) Males Females 0.402 0.616 0.392 0.672 0.380 0.572 0.400 0.593 Final Body Weights of Sacrificed Rata (g) Males Females 518 314 523 287 536 337 517 321 ii' OJ o m IT. r LEXOLDMON002722 o to 7z1 o o N </t 00 Ut . *" fttifaBIO*TEST }*%e. 37 9 e. Histopathologic Findings 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 examina tion 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 oc curred in the control as well as the rats fed Arodor 1260. O O i 6BRN002386 LEXOLDMON002723 falttihial IS I U I t > I Z&t**abyuci, `Jmc. 38 TABLE XDC TEST MATERIAL: Aroelor 1260 Two-Year Chronic Oral Toxicity Study - Albino Rats Histopathologic Changes * Three-Month Sacrifice ' Group: Control Num ber of Animals Organ Examined Findings 5 Males Trachea Lung Urinary bladder Tracheitis Chronic respiratory disease Hyperplasia 5 Females Lung Chronie respiratory disease Ave rage Incidence Grade 1 i.O 1 1.0 3 1.0 1 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 ' .' O GBRN002387 LEXOLDMON002724 jB I O - r fe b I JL&jtnaJiyu&i, Jc. 39 TABLE XX TEST MATERIAL: Aroclor 1260 Two-Year Chronic Oral Toxicity Study - Albino Rats Histopathologic Changes * Three-Month Sacrifice Croup: 100 ppm Number of Animals Organ Examined Findings 5 Males Trachea Lung Tracheitis Chronic respiratory disease 5 Females Trachea Lung Kidney Tracheitis ' Chronic respiratory disease Focal lymphoid infiltration Average Incidence Grade 4 1.0 2 1.0 3 2 - 1 1.0 * 1.0 1.0 All other tissues and organs were normal histologically. Grading System 0.5= minimal 1.0 s slight 2.0 a mild 3.0 moderate 4.0 severe 5.0 extreme ' 6BRN002388 LEXOLDMON002725 aiu I ea i y*c. 40 2. Six-Month Sacrifice . * a. Gro Pathologic Findings No outstanding differences were noted between test and control animals. m ' b. Organ Weight and Organ to Body and Organ to Brain Weight Ratio Data The results of the statistical analyses conducted on absolute 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 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 Aroclor 1260. 6BRN002389 LEXOLDMON002726 O Dietary Level of Aroclor 1260 (ppm) Control 1 10 100 oo TABLE XXI TEST MATERIAL: Aroclor 1260 Two-Year Chronic Oral Toxicity Study - Albino Rats Organ Weight and Ratio Data Six-Month Sacrifice Summary of Mean Values Organ: Liver _ , Organ Weight (g) Males Females 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 I4.8* 19.0* 24.4 15.1 10.5** 11.6 2.92** 3.31* 4.69* 3..74 3.08* 4.03 7.05** 9.45* 12.3 7.86 6.07 6.17 \ V c s n u r LEXOLDMON002727 4 Statistically significant difference at the 95 percent confidence level. G) * Statistically significant difference at the 99 percent confidence level. 00 TO z o o N W -0 O * jtvftnlu+L B 1 0 -T E S T Jt LEXOLDMON002728 O t a Dietary Level of Aroclor 1260 (ppm) Control 1 10 100 oG TABLE XXII . TEST MATERIAL* Aroclor 1260 Two* Year Chronic Oral Toxicity Study Albino Rata Organ Weight and Ratio Data Six-Month Sacrifice * Summary of Mean Value* . Organ: Kidney* 0 * Organ Weight (g) Males Females - Organ/Body Weight Ratio (g/100 g) Males Females 4.04 2.79 0.664 0.806 3.64 2.73 0.716 0.674% 3.85 2.35 0.670 0.684* 3.92 2.35 0.753 0.814 ' Organ/Brain Weight Ratio (g/g) Males Females 2,06 1.43 !.73 1.42 1.92 1.36 1.97 1.25 * Statistically significant difference at the 95 percent confidence level. G) DO 7J Z a o N <1 I I N LEXOLDMON002729 Ooo TABLE XXIII TEST MATERIAL: Arodor 1260 Two-Year Chronic Oral Toxicity Study - Albino Rata Organ Weight and Ratio Data Six-Month Sacrifice Summary of Mean Values Organ: Spleen Dietary Level of Aroclor 1260 (ppm) Control 1 ' 10 100 Organ Weight (g) Males Females 0.752 0.684 0.754 0.908 0.836 0.566* 0.636 0.443* Organ/Body Weight Ratio (g/100 g) Males Females 0.122 0.196 0.148* 0.220 0.146* 0.167 0.122 0.151 * Statistically significant difference at the 95 percent confidence level. Organ/Brain Weight Ratio (g/g) Males Females ' 0.384 0.350 ' 0.359 0.472 0.416 0.327 0.320 0 0.236* * G) CO X z o *0 IS) ( r i ! * 4 1 LEXOLDMON002730 o Dietary Level of Aroclor 1260 (ppm) Cont rol 1 10 100 o TABLE XXIV TEST MATERIAL: Arodor 1260 Two-Year Chronic Oral Toxicity Study - Albino Rata Organ Weight and Ratio Data Six-Month Sacrifice Summary of Mean Values ' Organ: Gonads O Organ Weight (g) Males Females 3.55 0.0960 3.23 0. 120* 3.56 0.0968 3.53 0.0710* Organ/Body Weight Ratio (g/100 g) Males Females 0.593 0.0279 0.636 0.0297 0.620 0.0287 0.686 0.0250 Organ/Brain Weight Ratio (g/g) Males Females 1.81 0.0492 . 1.54 0.0625* 1.77 . 0.0560 1.77 0.0378* * Statistically significant difference at the 95 percent confidence level. G) CO 7z0 o o N M fl w i ^ r t iI t y V ! Jrrfff.ff,;*! D I U I c 9 I \o table XXV ' TEST MATERIAL: Arodor 1260 ' Two-Year Chronic Oral Toxicity Study - Albino Rata .. Organ Weight and Ratio Data % Six-Month Sacrifice * Summary of Mean Values . Organ: Heart . Dietary Level of -Aroclor 1260 (ppm) Control 1 10 ICO Organ Weight (g) Males Females 1.70 1.05 1.45 1.12 1.63 1.05 1.49 1.06 Organ/Body Weight Ratio (g/100 g) Males Females Organ/Brain Weight Ratio (g/g) * Males Females 0.282 0.302 0.867 0.538 0.286 0.277 0.690 0.583 0.283 0.307 0.810 0.606 0.286 0.368** 0.749 0.564 yea 6Z00NHa9 ** Statistically significant difference at the 99 percent confidence level. \r O O K3 CO II Oo TABLE XXVI TEST MATERIAL: Aroclor 1260 Two-Year Chronic Oral Toxicity Study - Albino Rata Organ Weight', and Ratio Data Six-Month Sacrifice Summary of Mean Values ` Organ: Brain Dietary Level Final Body Weights of Organ Weight Organ/Body Weight Ratio of Sacrificed Rats Aroclor 1260 (g) (g/100 g) (g) (ppm)Males FemalesMales______ FemalesMales______ Females Control 1.96 1.95 0.320 6.560 ,> 613 348 1 2.10 1.92 0.412* 0.474* 509 405 10 2.01 1.73 0.349 0.504 575 . 343 100 1.99 1.88 0.382 0.650* 522 289 LEXOLDMON002732 G) * Statistically significant difference at the 95 percent confidence level. W * Z o o N W 0 U1 lI .' StUmtuaL B I O T E S T JialtMatAUti, }r%c. 47 O e. Histopathologic Findings Histopathologic examination of tissues and organs taken from all animals from both the control and 100 ppm groups was conducted. * m Tables XXVII and XXVIII 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 Aroclor 1260. O O 6BRNO02396 lexoi nMDNnn9733 B I 0 T 6 S f XaiAxalAxUi, Vie. 48 TABLE XXVII TEST MATERIAL: Aroclor 1260 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 Trachea Lung Liver Skeletal muscle Tracheitis Focal tracheitis Focal pneumonitis Hyperemia Focal pericholangitis Focal inflammation 2 2 1 2 1 1 1.5 1.0 0.5 1.0 1.0 1.0 5 Females Trachea Lung Liver Xidney Focal tracheitis Hyperemia Hype remia Pericholangitis Focal inflammation 1 . 1.0 2 2.5 1 1.0 1 0.5 1 1.0 All other tissues and organs were normal histologically. Grading System 0.5 a minimal 1.0 = slight 2.0 'mild 3.0 s moderate 4.0 severe 5.0 i extreme O 6BRN002397 LEXOLDMON002734 j i xanavuiyucu, jna. TABLE XXVIII TEST MATERIAL: Aroclor 1260 Two-Year Chronic Oral Toxicity Study - Albino Rats Histopathologic Changes - Six-Month Sacrifice Group: 100 ppm . Humber of Animals Organ Examined Findings Average Incidence Grade 5 Males Trachea Lung Liver Tracheitis Focal tracheitis Focal pneumonitis Hyperemia Hyperemia Focal pericholangitis 2 l 4 4 1 1. 2.0 0.5 1.0 1.5 1.0 0.5 5 Females Trachea Lung Liver Kidney Focal tracheitis Focal pneumonitis Hyperemia Hyperemia Focal pericholangitis Focal nephritis 2 O.S 2 ' 1.0 1 3.0 2 1.5 1 0.5 3 0.5 All other tissues and organs were normal histologically. \ Grading System 0.5 * minimal 1.0 slight 2.0 a mild 3.0 a moderate 4.0 a severe 5.0 a extreme * SBRN00239B LEXOLDMON002735 BIO T B S T Shc. 50 3. Twelve-Month Sacrifice a. Grata Pathologic Findings Cross 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 twelve month sacrifice are presented in Tables XXIX through XXXIV. t Statistically significant differences ere 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 1260. " BBRN002599 LEXOLDMON002736 o Dietary Level (ppm) Control 1 10 100 oo TABLE XXIX TEST MATERIAL: Aroclor 1260 Two-Year Chronic Oral Toxicity Study - Albino Rata 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 Organ/Brain Weight Ratio (g/g) Males Females 22.1 17.1* 20.0 28.8* 15.5 10.7* 13.6 14. 1 3.79 2.79** 3.30 4.26 3.52 3.01* 3.54 3.79 10.8 9.23 10.8 13.4* 7.72 5.76 7.28 8.52 * Statistically significant difference at the 95 percent confidence level. ** Statistically significant difference at the 99 percent confidence level. m oXI- G) to 73 Z D a o O M XL za o oNO a GO  Dietary Level (ppm) Cont rol 1 10 100 oo TABLE XXX TEST MATERIAL: Aroclor 1260 Two-Year Chronic Oral Toxicity Study - Albino Rate , . Twelve-Month Sacrifice Organ Weight and Ratio Data Summary of Mean Values . Organ: Kidneys Organ Weight (g) Males Females Organ/Body Weight Ratio (g/100 g) Males Females Organ/Brain Weight Ratio (g/g) Males Females 4.04 3.84 4.00 3.19 2.58** 2.78* 0.692 0.625 0.660 0.738 0.724 0.736 1.97 2.06 . 2.16 1.58 1.39 1.48 5.11* 2.81 0.758 0.755 2.38* 1.69 Statistically significant difference at the 95 percent confidence level. * Statistically significant difference at the 99 percent confidence level. LEXOLDMON002738 G) DJ 3zo0 o N O i LEXOLDMON002739 Oo TABLE XXX! TEST MATERIAL: Aroclor 1260 Two-Year Chronic Oral Toxicity Study - Albino Rate Twelve-Month Sacrifice ' Organ Weight and Ratio Data . Summary of Mean Values Organ: Spleen . Organ Weight Organ/Body Weight Ratio Organ/Brain Weight Ratio Dietary Level (g) (g/100 g) (g/g) (ppm)MalesFemalesMalesFemalesMalesFemales Control 0.778 0.796 0.133 0.183 0.380 0.396 1 0.756 0.460* 0. 122 0.129* 0.408 0.247* * 10 0.836 0.578 0. 139 0.150 0.457 0.308 100 0.785 0.474* 0.116 0.127* 0.365 0.284 * Statistically significant difference at the 95 percent confidence level. G) CO 30 z o o Mc o II N . ` | sI i i I l LEXOLDMON002740 O Dietary Level (ppm) Control 1 10 100 OO TABLE XXXII TEST MATERIAL; Aroclor 1260 Two-Year Chronic Oral Toxicity Study - Albino Rats . . Twelve-Month Sacrifice Organ Weight and Ratio Data Summary of Mean Values . Organ: Gonads Organ Weight (g) Males Females Organ/Body Weight Ratio (g/100 g) Males Females Organ/Brain Weight Ratio (g/g) Males Females 3.46 3.38 3.51 4.03** 0.116 0.103 0.112 0.088* 0.596 0.551 0.578 0.598 0.0275 0.0287 0.0294 0.0238 1.70 1.82 1.89 1.88 0.0574 0.0552 0.0584 0.0527 * Statistically significant difference at the 95 percent confidence level. ! ** Statistically significant difference at the 99 percent confidence level. a a Z o o N r o w r i I l I t ui % f i o Dietary Level (ppm) Control 1 10 100 oo TABLE XXXIII TEST MATERIAL: Aroclor'1260 Two-Year Chronic Oral Toxicity Study - Albino Rata . Twelve-Month Sacrifice Organ Weight and Ratio Data - Summary of Mean Values. Organ: Heart Organ Weight (g) . Males Females Organ/Body Weight Ratio (g/100 g) Males Females Organ/Brain Weight Ratio (g/g) Males Females . I*71 1.68 1.59 1.86 1.23 1.07 1.16 1.27 0.293 0.273 0.261 0.275 0.287 0.301 0.307 0.340 0.835 0.902 0.845 0.868 0.611 0.575 0.620 0.760 m oXI- G) to 7} Z a Do IS) O z C a C o oK3 4^ LEXOLDMON002742 Ooo Dietary Level (ppm) Cont rol 1 10 100 . TABLE XXXIV TEST MATERIAL: Arodor 1260 Two-Year Chronic Oral Toxicity Study - Albino Rats ' Organ Weight and Ratio Data . . Twelve-Month Sacrifice Summary of Mean Values ' Organ Weight (g) Males Females Organ: Brain Organ/Body Weight Ratio (g/100 g) Males Females Final Body Weight of Sacrificed Rats (grams) Males Females 2.04 2.02 0.349 0.460 .584 439 1.8? 1.86 0.304 0.522 616 356 1.88 1.90 0.310 0.493 607 385 2.15 1.67** 0.318 0.449 675 372 ** Statistically significant difference at the 99 percent confidence level. CD CD Z o N O Ul w iA ijm c'rcp x S31" 0 1 8 Uo*l c. Histopathologic Findings ' 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 hisopathologic 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 Aroclor 1260. GBRN0D2406 LEXOLDMON002743 90 e TABLE XXXV TEST MATERIAL: Aroelor 1260 Two-Year Chronic Oral Toxicity Study Albino Rats Histopathologic Changes Twelve-Month Sacrifice Croup: Control . Number of Animals 5 Males 5 Females Organ Examined Trachea Lung Urinary Bladder Trachea Lung . Colon Findings Incidence Tracheitis Chronie respiratory disease Calculus 1 2 1 Tracheitis Chronic respiratory disease Parasites 1 1 1- Average Grade 1.0 1.0 1.0 1.0 1.0 1.0 - All other tissues and organs were normal histologically. Grading Svstem 0.5 : minimal 1;0 s slight 2.0 * mild 3.0 s moderate 4.0 s severe 5.0 s extreme . O BBRN002M07 LEXOLDMON002744 SttddtiiniaL B l O T 5 F XauonatA'UM. 'J*&. i'i TABLE XXXVI TEST MATERIAL: Arocior 1260 Two-Year Chronic Oral Toxicity Study - Albiao Rats Histopathologic Changes Twelve-Month Sacrifice Croup: 100 ppm Number of Animals 5 Males 5 Females Organ Examined Trachea Lung Kidney Liver Trachea Lung Findings Incidence Tracheitis Chronic respiratory disease Focal lymphoid infiltration Vacuolar change of random cells l 3 l 1 Tracheitis Chronic respiratory disease 1' 1 Ave rage Grade 1.0 1.0 1.0 1.0 1.0 ` 1.0 All other tissues and organs were normal histologically. Grading System 0.5 * minimal 1.0 = slight 2.0 mild 3.0 s moderate 4.0 * severe 5.0 extreme . . GBRN002M08 LEXOLDMON002745 .SfvCuU'ual BtO'TEST ^abanatytiM, Sue. 60 Q 4. Final Sacrifice a. Gross Pathologic Findings Gross 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 XXXVII through XLII. Statistically significant differences are designated by asterisks following the test group value. . - Absolute liver weights and liver to body weight or liver . to brain weight ratios were significantly elevated in those rats fed 100 ppm O Arodor 1260. Other 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 1260 . O GBRN002U09 LEXOLDMON002746 .jitditilniaL B ( O T E S T J&i&afaioi, }*e. LEXOLDMON002747 ' ietary Level (ppm) ontrol 1 10 00 O TABLE XXXVII ' TEST MATERIAL! Aroclor 1260 Two-Year Chronic Oral Toxicity Study - Albino Rats Organ Weight and Ratio Data ' l . Summary of Mean Values Final Sacrifice Organ: Liver Organ Weight (g) Males Females 22.0 16.3 Organ/Body Weight Ratio (6/100 g) Males Females 3.47 3.05 - 22.0 16.6 3.40 3.35 24. 1 18. 1 2. 87* 3. 19 29.9** 22.7** 4.67** 4.42** : Statistically significant difference at the 96 percent confidence level. 1 Statistically significant difference at the 99 percent confidence level. Q 0 TO Z o o M tI c. o Organ/Brain Weight (g/g) Males Females 10. 10 8.42 9.93 8.62 11.20 9.26 13.40* 11.60* )ictary Level (ppm) Control 1 10 100 O . TABLE XXXIX TEST MATERIAL: Arodor 1260 Two-Year Chronic Oral Toxicity Study - Albino Rata ' Organ Weight and Ratio Data Summary of Mean Values * Organ Weight (B) Males Females Final Sacrifice Organ: Spleen Organ/Body Weight Ratio (B/100 g) Males Females 1.15 1. 17 0.96 0.72 0. 182 0. 178 0. 181 0. MB 1.09 0.89 0.83 0.75 0. 131 0. 138 0. 142 0. 146 o -' ; I t \ | . [ I). | I _ v Organ/Brain Weight Ratio ^ (b/b) Males Females 0.520 0.529 0.492 0. 370 0.509 0.428 0.400 0.379 LEXOLDMON002748 O W JO zo oo o IcS) O Dietary Level (ppnri) Control 1 10 100 o TABLE XL TEST MATERIAL} Aroclor 1260 Two-Year Chronic Oral Toxicity Study - Albino Rata . . Organ Weight and Ratio Data i Summary of Mean Values Organ Weight Males (B) Females 2.52 0. 123 Final Sacrifice Organ: Gonads Organ/Body Weight Ratio (g/100g) Males Females 0. 397 0.0222 3.56* 0. 140 0.550* 0.0317 3. 36* 0. 177 0.400 0.0338 2.97 0. 113 0. 464 0.0229 o Organ/Brain Weight Ratio (g/g) Males Females 1. 15 0.0628 1.61* 0.4)718 1.56* 0.0900 1.33 0.0584 iJ Statistically significant difference at the 96 percent confidence level. LEXOLDMON002749 CD 00 O a N O Dietary Level (ppm) Control l 10 100 o TABLE XLI TEST MATERIAL! Aroclor 1260 Two-Year Chronic Oral Toxicity Study - Albino Rata Organ Weight and Ratio Data l Summary of Mean Valuea Final Sacrifice Organ; Heart Organ Weight Males (g) Females Organ/Body Weight Ratio (b/*oo g) Males Females 1.87 1.54 0.294 0. 288 1.98 1.45 0. 304 0.294 1.90 1.58 0.225** 0.279 2.00 1.49 0.313 0.288 o Organ/Brain Weight Ratio (g/g) Males Females 0.860 0.795 0.893 0.747 0.884 0.809 0.904 0.764 ** Statistically significant difference at the 99 percent confidence level. LEXOLDMON002750 ttno az o o N II C4 uO 1 S 3 1 * O 1B o ' Dietary Level (ppm) Control 1 10 100 o TABLE XLII TEST MATERIAL: Aroclor 1260 Two-Year Chronic Oral Toxicity Study - Albino Rats * ' . Organ Weight and Ratio Data i 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 2.21 2. 15 2. 22 1.94 1.96 1.95 0.343 0.255** 0.346 0.407 0.347 0.378 654 845** 641 525 584 644 4C *-* Statistically significant difference at the 99 percent confidence level tn n m oX I D z o a N i- O Z o oK3 cn ! O' O' Sniullual B l O - T E S T Dtc. 67 c. Histopathologic Findings Histopathologic examination of tissues and organs - taken from all animals sacrificed after 24 months on test was conducted. Tables XLIII through XLVI list all histopathologic changes noted.* Table XLVII contains the results of the histopathologic examination of the urinary bladders. Significant liver injury was found in animals fed 100 ppm Aroclor 1260 (T-III). 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-III group. The vacuolar change was not seen in the control animals but was observed occasionally in livers from T-I (lppm) and T-II (10 ppm) _ animals. It was frequent in the T-III animals. This lesion is morphologically indicative of fatty degeneration. Formalin-frozen sections of livers from represenative animals which displayed vacuolar changes were stained with ' Oil Red 0 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 homogenous cytoplasm. The hyperplasia was associated with the same cells and appeared to be an * GBRND02M15 LEXOLDMON002752 SfuLti&ual B I O * T E S T JsJuyiaiiUei, !)nc. 68 extension of the hypertrophic lesion. The hyperplastic cells were also usually hypertrophic. 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-Iand T-II groups are lesions of spontaneous disease and are not related to the Aroclor 1260. This level of liver disease is not unusual in old animals. Hyperplasia of the urinary bladder was found in an animal from the control group. This finding was not present in any of the rats fed Aroclor 1260. All of the other lesions in other tissues found in these animals are related to spontaneous disease and they are not unusual for old rats. Donovan E. Cordon, D. V. M. , Ph. D. Diplomate, American College of Veterinary Pathologists GBRN002m6 LEXOLDMON002753 LEXOLDMON002754 Number of Animals 1 Males G) U X Z o N r M. O TABLE XLIII TEST MATERIALt Aroclor 1260 Two-Year Chronic Oral Toxicity Study Albino Rata 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 ' .. .. . 1 Incidence 3 3 9 1* 2 1 3 8 2 2 1 1 .2 o t ! Average Grade 1.0 1.0 1.0 1.0 1.0 1.01.0 1.0 1.0 1.0 1.0 ' 1.0 1.0 1.0 1.0 1.0 II i * f O Ooo r is a i-018 r f w r t ' TABLE XLIII continued TEST MATERIAL! Aroclor 1260 Two-Year Chronic Oral Toxicity Study - Albino Rate Histopathologic Changes Final Sacrifice Group: Control Number of Animals Organ Examined Findings Incidence Average Grade 14 Females (D CO X z o o N C CO Heart Trachea Lung Liver Stomach Colon Spleen Uterus Kidney Ovary Adrenal Gland Salivary Gland . 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 .' Telangiectasis Nodular hyperplasia Chronic fibrosis and atrophy All other tissues and organa were normal histologically. Grading System * * 0. 5 = minimal 1 n _ .. i : . i . 2.0 = mild 4.0 = severe 7" 9 13 3 2* I 2 3 5 1 4 3 6 1 l 9 4 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 1.0 1.0 1.0 Os| LEXOLDMON002755 LEXOLDMON002756 Number of Animals 11 Males Gl a n z o o N -0 O TABLE XLIV TEST MATERIAL: Arodor 1260 I Two-Year Chronic Oral Toxicity Study - Albino Rata Histopathologic Changes Final Sacrifice Croup: 1 ppm < Organ Examined Heart Trachea Lung Liver . Pancreas Stomach Spleen Lymph Node Kidney Testes Prostate Seminal Vesicle Findings Chronic focal myocarditis Tracheitis Chronic respiratory disease Focal hepatitis Focal scarring Hemosiderosis Chronic focal pancreatitis Acute focal gastritis Hemosiderosis Congestion . Chronic nephritis Testicular degeneration Periarteritis Inflammation Inflammation . Incidence 4 7 10 1. 1 1 2 .1 1 1 7 1 2 4 1 * 1I o Average Grade 1.0 1.0 2.0 1.0 1.0 1.0* 1.0 3.0 1.0 1.0 2.0 2.0 1.0 2.0 . 2.0 LEXOLDMON002757 Oo Number of Animals 11 Males TABLE XLIV continued TEST MATERIAL: Aroclor 1260 Two-Year Chronic Oral Toxicity Study - Albino Rata Histopathologic Changes Final Sacrifice Group: 1 ppm ' Organ Examined Adrenal Gland Findings Nodular hyperoplasia Focal fatty change Incidence 2 2 14 Females Heart Trachea Lung Liver Stomach tn 01 7) Z o a M -c M O Chronic focal myocarditis Chronic focal myocarditis Tracheitis Chronic respiratory disease Focal fibrosis Focal lymphoid infiltration Ductile hyperplasia Congestion Vacuolar change (fatty) Chronic gastritis Acanthosis . * . 3 1 9 13 1 1 1 1 1 2 o Average Grade 1.0 1.0 1.0 3.0' 1.0 1.0 1.0 1.0 0.5 1.0 2.0 1.0 1.0 LEXOLDMON002758 Number of Animals 14 Females GJ 2toJ Z o a IS) E N O TABLE XLIV continued TEST MATERIAL: Aroclor 1260 Two-Year Chronic Oral Toxicity Study - Albino Rata Histopathologic Changes Final Sacrifice Group: I ppm * Organ Examined Stomach Colon Spleen Lymph Node Kidney . Uterus Adrenal Gland Findings Ulceration and acanthosis Parasites Hemosiderosis Hyperplasia Congestion Chronic nephritis Vacuolar change (fatty) Metritis Telangiectasis Nodular hyperplasia Congestion Incidence 1 1 II 1 1 3 1 4 9 3 1 All other tissues and organs were normal histologically. 0. 5 = minimal 1.0 = slight Grading System 2.0 = mild 4.0 = severe 3. 0 = moderate ' 5. 0 = extreme O Average Grade 1.0 1.0 1.0 1.0 1.0 2.0 . 1.0 1.0 1.0 1.0 1.0 LEXOLDMON002759 O Number of Animals 7 Males * TABLE XLV TEST MATERIAL: Aroclor 1260 Two-Year Chronic Oral Toxicity Study - Albino Rata Histopathologic Changes Final Sacrifice Group: 10 ppm > Organ Examined Heart Trachea Lung . Liver Stomach Spleen Kidney Prostate Adrenal Gland Findings Chronic focal myocarditis Tracheitis Chronic respiratory disease Suppurative pneumonia Vacuolar change (fatty) Chronic gastritis Acanthosis Hemosiderosis Chronic nephritis Inflammation Nodular hyperplasia Incidence 3 2 5 1. 2 1 2 3 6 2 1 14 Females G) DO 3 Za a ro c. M N Heart Trachea Lung Chronic focal myocarditis Thracheitits ' Chronic respiratory disease I 3 8 14 o Average Grade 1.0 1.0 1.0 3.0 1.0 1.0 1.0 1.0 1.0 1.0 . 1.0 Il I !I % i 1.0 1.0 1.0 Sndttt**2* 1- B l Q I 6 S f ^*ito*alor'uci, 3*e. LEXOLDMON002760 O TABLE XLV continued TEST MATERIAL: Aroclor 1260 Two-Year Chronic Oral Toxicity Study - Albino Rata Histopathologic Changes Final Sacrifice Group: 10 ppm * Number of Animals Organ Examined Findings Incidence 14 Females 01 0) 7i z - oo--------------N) N <A Liver Pancreas Stomach Spleen Kidney Utc rus Pituitary Adrenal Gland . Vacuolar change (fatty) Focal hyperplasia Chronic focal pancreatitis Periarteritis Acanthosis Hemosiderosis Chronic nephritis Metritis Congestion Telangiectasis Nodular hyperplasia Congestion 1 1 1 1 1 12 10 . 7 1 7 1 1 All other tissues and organs were normal histologically. .5 = minimal Grading System 2.0 = mild '1 4.0- severe e Average Grade 1.0 1.0 3.0 3.0 1.0 . 1.0 1.0 2.0 1.0 1.0 1.0 1.0 o I o o . TABLE XLVI TEST MATERIAL: Aroclor 1260 Two-Year Chronic Oral Toxicity Study - Albino Rata Histopathologic Changes Final Sacrifice Group: 100 ppm Number of Animals Organ Examined Findings Incidence Average Grade 10 Males Heart Trachea Lung Chronic focal myocarditis Tracheitis Chronic respiratory disease Congestion 5 8 9 1 1.0 1.0 2.0 1.0 Liver Vacuolar change (fatty) Focal degeneration 2 2.0 1 1.0 Congestion 3 2.0 Centrolobular hypertrophy .2 Telangiectasis 1 Pancreas Chronic focal pancreatitis 2 Stomach 1 Inflammation 2 Acanthosis 2 1. Spleen Kidney Hemosiderosis Focal lymphoid infiltration 7 1 m COn oX I D o l\) O N Z o oK3 Calcified concretions in pelvis 1 1.0 1.0 1.0 2.0 1.0 1.0 1.0 1.0 1.0 O) Oo . TABLE XLVI continued TEST MATERIAL: Arodor 1260 ' Two-Year Chronic Oral Toxicity Study - Albino Rale * Histopathologic Changes Final Sacrifice Group: 100 ppm* Number of Animals 10 Males Organ Examined Kidney (continued) Testes Prostate Thymus . Adrenal Gland Findings Calcified concretions in pelvis Aspermia Inflammation Cyst Telangiectasis Nodular hyperplasia Incidence 1 1 1 1. 3 1 o \ ' ( 4 Average Grade 1.0 1.0 1.0 1.0 1.0 1.0 LEXOLDMON002762 IS Females G) to 73 oo Is) r is) Heart Trachea Lung Liver I Chronic focal myocarditis Tracheitis Chronic respiratory disease Congestion Edema Vacuolar change (fatty) I 5 8 11 1 1 5 1.0 1.0 1.0 1.0 1.0 1.0 -I LEXOLDMON002763 Oo Number of Animals 15 Females GJ U3J) z o o C o ' TABLE XLVI continued TEST MATERIAL: Aroclor 1260 Two-Year Chronic Oral Toxicity Study - Albino Rais Histopathologic Changes Final Sacrifice Group: 100 ppm* Organ Examined Liver (continued) Pancreas Spleen Kidney Uterus Pituitary Adrenal Gland Parathyroid Findings Incidence Focal hyperplasia Chronic inflammation of liver capsule Centrolobular hypertrophy Necrosis Ductile cell hyperplasia, portal fibrosis and widespread eosinophil inclusions in hepatocyte cytoplasm Chronic focal pancreatitis and periarteritis Hemosiderosis Chronic nephritis Metritis Congestion Telangiectasis Nodular hyperplasia Congestion Hyperplasia 4 1 5 2. 1 1 9 8 7 1 6 1 1 1 All other tissues and organs were normal histologically. i Grading System o Average Grade 1.0 1.0 1.0 2.0 1.0 3.0 2.0 1.0 1.0 1.0 1.0 1.0 1.0 - 1.0 1 LEXOLDMON002764 !i O Group C T-I (1 ppm) T-1I (10 ppm) T-III (100 ppm) o TABLE XLVII TEST MATERIAL: Arodor 1260 Two-Year Chronic Ora! Toxicity Study - Albino Rata Histopathologic Changes of the Urinary Bladder Final Sacrifice Number Sex Examined Findings* Incidence M 11 F 14 Proteinaceous plug (34) Focal epithelial hyperplasia (62) 1 1 M 10 F 11 M7 F 14 Proteinaceous plug (66. 105. and 107) None Proteinaceous plug (187) None 3 - 1 - M 10 F 14 Proteinaceous plug (271) None 1 - * Individual animal numbers are shown in parentheses 1.0 2.0 BJ 3.0 71 Z o o N N Grading System minimal or trace 4.0= severe niild 5.0 = extreme moderate I I Average Grade 1.0 m me *4 j*om*ua* o i w * e * xi.wi'wiHtft, G. Detailed Description of Tumor Findings Turner data for individual animals including location, weight and pathologic classification are presented in Tables XLVIII through LI. None of these tumors could be related to the ingestion of Aroclor 1260 and are considered normal for a random population of rats this age. GBRN002M28 LEXOLDMON002765 TABLE XLVIII TEST MATERIAL: Aroclor 1260 Two-Year Chronic Oral Toxicity Study - Albino Rata Description of Tumor Findings Group: Control Animal ! Cumber and Sex Location Weight (grams) Size (cm) Classification Months on Test ` 1-M 2-M ' Abdomen Pancreas 11.76 - Mammary fibroadenoma Adenocarcinoma 24 24 ;6-f 47-F . S8-F Abdomen i Lymph node J Abdomen 50-F Abdomen 52-F i 59-F , 64-F 66-F cn w oz a n.n N <0 Abdomen Abdomen Adrenal gland Abdomen Abdomen 64.98 35.09 - - - l - 88.92 230.00. . 8x1x2 5x2x2 ' - 2x2x1 2x2x3 , - 13 x 11 x 4 13,x 11x^4 Mammary fibroadenoma , Mammary fibroadenoma Reticulum cell sarcoma Mammary fibroadenoma Mammary fibroadenoma Mammary fibroadenoma Mammary fibroadenoma Pheochromocytoma Fibroadenoma ' Mammary adenoma . 24 24 24 7 24 24 24 24 LEXOLDMON002767 O Animal Number and Sex 99-M 127-F 128-F 138-F 141-F 151-F 152-F Location Pituitary Pituitary Abdomen Pituitary Abdomen Abdomen Pituitary Ovary Abdomen Abdomen az o a N C w o > o TABLE XLDC 0 TEST MATERIAL] Aroclor 1260 Two-Year Chronic Oral Toxicity Study - Albino Rata Description of Tumor Findings Group: 1 ppm Weight (grams) 25.00 .60.80*' 20.07 - 14.89 540.00 Size (cm) - - 6x3x1 5x6x2* - - 13x15x2 ' Classification ^ Chromophobe adenoma l Chromophobe adenoma ` Mammary fibroadenoma 4* t Chromophobe adenoma " Mammary fibroadenoma .< Mammary fibroadenoma i Chromophobe adenoma Adenoma Mammary fibroadenoma i Mammary fibroadenoma Q Months on Test 20 24 21 10 *24 24 24 22 I o I O Animal Number and Sex ` ' 205-F 208-F 213-F 216-F 220-F 221-F TABLE L TEST MATERIAL: Arodor 1260 Two-Year Chronic Oral Toxicity Study - Albino Rata Description of Tumor Findings Group: 10 ppm Location Weight (grams) Abdomen 190.00 Pituitary - Abdomen .- Right shoulder 138.00 Abdomen Pituitary 9. 57 - Submaxillary region Abdomen 14.44 29.0 Size (cm) 9x5x4 - 2x3x1 3x5x2 Classification Mammary fibroadenoma < Chromophobe adenoma 1 Mammary fibroadenoma ( ^ Subcutaneous tumor ^'Mammary fibroadenoma / Chomophobe adenoma 1 Fibroadenoma Mammary fibroadenoma o Months on Test 24 24 24 23 24 24 GBRN002M3 LEXOLDMON002768 1 aa 11 Animal Number and Sex V 22-F A 233-F 234-F Location Left femoral region Pituitary Abdomen Panereaa O * TA. BLE L continued TEST MATERIAL: Aroclor 1260 Two-Year Chronic Oral Toxicity Study - Albina Rate Description of Tumor Findings Group: 10 ppm Weight (grams) 56.00 Size (cm) 6x8x2 Classification l/Subcutaneous tumor 60.82 6x4x3 V Chromophobe adenoma ^ Mammary fibroadenoma ^ Islet cell adenoma 9 Months on Test 6 24 24 e LEXOLDMON002769 0 DO 71 Z o M X I'd A Animal Number and Sex 244-M 264-M 281-F 293-F 294-F 301 -.Fi Location Pancreas Pancreas Abdomen Liver Abdominal cavity Liver T) TABLE LI TEST MATERlALi Aroclor 1260 Two-Year.Chronic Oral Toxicity Study - Albino Rata Description of Tumor Findings Group: 100 ppm Weight (grams) 35.04 50.75 1. Size (cm) '- 6x4x2 6x4x3 - Classification 1 Adenoma jXIslet cell adenoma t/Mammary fibroadenoma Lymphosa rcoma x' Fibroma Lymphosarcoma & . Months on Test 24 21 24 23 24 23 GBRND02M33 * m Xo I D O i . Z o oK3 I Animal Number and Sex 302-F 308-F 311-F Location Lymph node Pituitary Abdomen 312-M 314-F Pituitary Abdomen TABLE LI continued TEST MATERIAL: Aroclor 1260 Two-Year Chronic Oral Toxicity Study - Albino Rats Description of Tumor Findings Group: 100 ppm Weight (grams) 14.00 26.00 Size (cm) - - 4x3x2 1x2x1 - 5x4x3 Classification y Lymphosarcoma v' Chromophobe adenoma `'Mammary fibroadenoma . iMammary fibroadenoma ''chromophobe adenoma ^ Mammary fibroadenoma Months on Test 24 24 24 24 24