Document kmpmg5oe2erJko01RED7BxJRE

9ru$u6&iual BIO -TEST J^alkmibyiies, Dm. 1810 FRONTAGE ROAD NORTHBROOK, ILLINOIS 60062 November 12, 1971 Mr. Elmer P. Wheeler Monsanto Company 800 North Lindbergh Boulevard St. Louis, Missouri 63166 Dear Mr. Wheeler: Re: 1BT No. B7298 - Two-Year Chronic Oral Toxicity Study with Aroclor 1260 in Albino Rats We are submitting herewith our laboratory report dated November 12, 1971, prepared in connection with the above study. Very truly yours JCC/kjl J. C. Calandra President 0365669 TOXSTUDIES1525 PROJECT NO! report; file --" f SfuSuMAoai BIO -TEST JjsJwiaiyue&. Snc. 1610 FRONTAGE ROAD NORTHBROOK. ILLINOIS 60062 REPORT TO MONSANTO COME&fp TWO-YEAR CHRONIC ORAL TOXICITY WITH AROCLOR 1260 . >?-*' IN ALBINO RATS NOVEMBER 12, 1971 X IBT NO. B7298 i O o li 03b^b7 TOXSTUDIES1526 . SJLifcd . B 10 - T E S T fatwuiWiiM, Sm. Q REPORT TO MONSANTO COMPANY TWO-YEAR CHRONIC ORAL TOXICITY WITH AROCLOR 1260 IN ALBINO RATS NOVEMBER 12, 1971 IBT NO. B7Z98 I, 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. \ TOXSTUDIES1527 QnduUtial B I O - T E S T JohviaiMiei, 9*tc, 2 O XI. 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 Aroclor 1260. Food consumption and body weight gains were not altered at any level of Aroclor 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 Aroclor 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 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. 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-III group. Histologic examination of the livers from the T-III 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 Aroclor 1260. 03tot>t>TZ TOXSTUDIES1528 S.uluilual B I 0 - T E 5 T lah&iata.MeA, 9hc. 3 O 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: rWVfo PPhhiillipip"'S; mith", B. S. Assistant Toxicologist Rat Toxicity Report approved by: Jkmks B. Plank Settlor Group Leader Rat Toxicity Paul L. Wright, ph. D. Section Head, Toxicology L. Keplir^g^, Ph. Manager, Toxicology November 12, 1971 lam;sjn 0365673 TOXSTUDIES1529 B 1 O - T E S T lahmai^uei, 9nc. 4 O HI. Procedure A. Experimental Animals ' The animals employed in the test were Charles River strain5* albino rats. Four hundred rats (ZOO 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 spect 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 I. TABLE I . TEST MATERIAL: Aroclorl260 Two-Year Chronic Oral Toxicity Study - Albino Rats Outline of Experiment Number of Animals Dietary Level GroupMaleFemale(ppm) Control T-I 50 50 50 50 ' None Administered 1 T-Il 50 50 10 T-m 50 50 100 * Charles River Breeding Laboratories North Wilmington, Mass. 0 36S67*. TOXSTUDIES1530 B I O - T E 5 T Jtakofuittyii&i, Due, 5 O 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 Aroclor 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 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 ' . 1 - 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 tions, hemotocrit value, erythrocyte count and both total and differential * Purina Rat Chow, Ralston Purina Co, , St, Louis, Mo. 0365675 TOXSTUDIES1531 Pn&tUtial B I O - T E S T lakwttyuei, $ttc. 6 O leukocyte counts, were conducted upon five males and five females from both the control and 100 ppm groups. 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. 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. 036 56 76 TOXSTUDIES1532 B 1 O - T c 5 T lauoAat&'Uet, Stic. 7 Absolute organ weights were 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 "f'-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. 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. O 036t>677 TOXSTUDIES1533 9tuluit-ucU B I O - T E S T Jahoiat&uai, 9kg. 8 Q 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, 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 and pathologic classification were recorded. 9 TOXSTUDIES1534 HtuLulnial B I O - T E S T Jol&itU&uel, 9nc, 9 IV. Results A. Body Weights and Weight Gains 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 0365679 TOXSTUDIES1535 dietary Level of Aroclor 1260 (ppm) Sex Control , M F M F 10 M F 100 M F QQ 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 Body Weight 90-Day (grams) Total Weight Week: Gain 0 1 2 3 4 5 6 7 8 9 10 11 12 13 (arams/rat) 133 203 245 313 362 373 391 409 424 440 440 449 467 474 136 178 190 219 244 254 259 265 270 276 281 278 290 288 133 192 250 322 361 374 394 416 428 448 450 474 479 490 136 167 189 218 241 252 256 261 268 273 277 281 290 288 133 204 245 317 368 382 400 417 436 448 461 467 475 481 136 174 190 217 242 254 260 263 268 274 281 279 285 288 341 152 357 152 348 152 133 208 247 319 363 375 394 425 437 451 460 479 486 500 136 173 188 222 240 253 258 262 265 267 270 275 275 280 367 244 UJ a<&-p o TOXSTUDIES1536 Dietary Level of Aroclor 1260 (ppm) Sex Control M F 1M F 10 M F 100 M F 4 498 297 516 298 496 291 522 289 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: 5 6 '7 8 9 10 11 533 565 593 622 642 667 688 310 322 333 345 359 374 383 547 578 600 628 643 668 688 307 314 321 333 340 353 367 526 ' 551 581 60 6 633 660 685 306 314 331 340 358 370 381 555 580 607 633 650 681 707 302 307 314 326 333 342 347 12-Month Total Weight Gain 12 (grams/rat) 701 568 390 254 699 ' 379 709 388 566 243 576 252 717 584 363 227 c o <T TOXSTUDIES1537 Dietary Level of Aroclor 1260 (ppm) Sex Control M F 1M F 10 M F 100 M F 13 728 426 721 390 728 416 746 380 TABLE II continued TEST MATERIAL: Aroclor 1260 Two-Year Chronic Oral Toxicity Study - Albino Rats Body Weight and Total Weight Gain Data Summary of Mean Values 14 15 16 Body Weight (grams) Month: 17 18 19 20 21 22 746 759 768 769 767 760 758 739 726 444 466 481 500 515 533 547 551 550 740 760 768 776 774 762 753 733 718 427 466 433 445 476 481 493 514 530 745 776 761 768 780 774 761 735 715 434 482 449 473 508 519 530 536 542 760 772 775 774 769 760 750 733 714 386 417 414 435 453 471 481 500 507 23 687 564 715 484 683 536 711 485 24-Month Total Weight Gain 24 (grams/rat) 642 509 551 415 654 521 525 385 645 584 641 537 512 448 508 401 OO'' 0* rj TOXSTUDIES1538 B 1 O - T E S T Ja&M&Vued, 9*tc. 13 B. Food Consumption The data obtained from the food consumption measurements conducted during the first 12 months of feeding are summarized in Table III. 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. 0 3650Q3 TOXSTUDIES1539 B I O T E S T XahyxitvUGi, St GO TABLE m TEST MATERIAL: Aroclor 1260 Two-Year Chronic Oral Toxicity Study - Albino Rats Food Consumption Data Summary of Mean Values Food Consumption >ietary Level of (grams/rat/seven days) Average Food Aroclor 1260 Week: Consumption fppm) Sex 1 2 3 4 5 6 7 8 9 10 11 12 13 (grams/rat/seven davsr Control M 94 160 175 163 137 137 225 197 204 188 191 194 196 F 73 140 144 107 104 133 208 154 165 151 146 150 151 174 140 i M 118 154 151 169 201 116 200 198 201 193 189 187 194 F 95 118 97 139 160 107 162 139 165 149 150 143 147 175 136 * 10 M 106 146 144 142 190 136 196 214 214 192 191 199 200 F 94 124 128 124 179 90 190 167 155 151 150 149 152 175 143 100 M 121 150 156 117 187 124 121 190 196 186 184 199 189 F 89 93 123 151 151 101 193 136 140 144 144 147 146 163 135 'j' cCCr TOXSTUDIES1540 SfuhtU'ual B IO -T E S T /<; dietary Level of Aroclor 1260 (ppm) Sex 4 Control M 196 F 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 davs) 189 168 147 163 184 179 170 187 154 136 121 138 152 160 141 127 176 142 200 189 192 179 181 182 172 184 163 141 163 160 153 157 143 132 186 151 191 . 188 193 197 197 168 164 196 138 145 144 144 151 136 139 141 186 142 170 180 188 186 1 166 181 188 180 127 147 144 134 132 162 149 139 ` 180 143 o o-J-1 ae-c O' TOXSTUDIES1541 HnduibUal B I O T E S T Ja&Maiostiei, $nc. 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. 03b5bt> TOXSTUDIES1542 0D 1 - T E 5 T 2alvyiaityi<c4-, Dhc. Dietary Level (ppm) Sex Control M F 1M F. 10 M F 100 M F TABLE IV TEST MATERIAL: Aroclor 1260 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 0 00 2 1 76 0 00 1 3 5 7 00 1 1 4 7 5 000 2 3 3 6 1 10 2 4 7 8 0 00 3 2 4 5 J 00 2 2 8 6 0 22 0 3 5 7 22-24 9 3 8 5. 6 3 9 4 Vi Total Dead Number Tested1* 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. TOXSTUDIES1543 SnduiUial B 1 O - T E S T lobyialoAiei, 9*tc. 18 D. Hematologic and Clinical Blood Chemistry Studies Mean male and female hematologic and clinical blood chemistry- data are summarized in Tables V through IX. Values for all parameters investigated were within the normal range for the albino rat. No significant differences between test and control values were observed. , TOXSTUDIES1544 sa1 o i av r wi w o Dietary Level (ppm) Control Sex 3 M 14.0 F 9.1 TABLE V TEST MATERIAL: Aroclor 1260 Two-Year Chronic Oral Toxicity Study - Albino Rat9 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 10.1 11. 1 9.9 11. 2 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 M 10.8 13. 1 7.9 12.8 8.6 8.4 7. 5 8. 1 8.0 7.6 8.0 7.6 100 F 13. 2 8.2 7.9 6.5 7.8 7.4 7. 3 7.5, 7. 3 7.5 7.4 6.4 r c <r occ> TOXSTUDIES1545 W IS 3 1.-O I 9 P W '/ Dietary Level (ppm) Sex 3 M 17. 1 Control F 16.9 TABLE VI TEST MATERIAL: Aroclor 1260 Two-Year Chronic Oral Toxicity Study - Albino Rats Hematologic Data Summary of Mean Values Hemoglobin Concentration (g/100 ml) Month: 6 9 U 18 24 Hematocrit Value (%) Month: 3 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 18 41 42 M 16. 1 17. 2 14. 0 15. 3 15.9 14.5 100 F 16.3 17.0 13. 7 15.6 15. 3 12.9 49 47 43 43 41 48 47 41 44 39 24 35 38 38 32 o wa v> o& rov TOXSTUDIES1546 fHduOtiai b l O - l t b l o oQ Dietary Level (ppm) Sex 3 M 82.0 Control F 83.0 TABLE Vn TEST MATERIAL: Aroclor 1260 Two-Year Chronic Oral Toxicity Study - Albino Rats Hematologic Data Summary of Mean Values Differential Leukocyte Count (Number of Cells per Hundred) Lymphocytes Neutrophils 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 31.6 7.6 10.0 19.4 17.0 17.4 34.2 o OO'' O' <0 T0XSTUDIES1547 M uil-ual B IO -TE S T A CO CO oo Dietary Level (ppm) Control Sex 3 M 0.6 F 0.6 TABLE VII continued TEST MATERIAL: Aroclor 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 18 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 o CD M 0.0 0.0 0.0 0.0 0.4 100 F 0.0 0.0 0.0 0.0 0.4 0. 2 1.4 0.8 1.0 1.2 1.0- 0.4 0.4 0.8 1.6 0.0 TOXSTUDIES1548 j. s 31 o i a wc o o 1 o o O TABLE VII continued TEST MATERIAL: Aroclor 1260 Two-Year Chronic Oral Toxicity Study - Albino Rats Hematologic Data Summary of Mean Values Dietary Differential Leukocyte Count (Number of Cells per Hundred) Basophils Level Month: (ppm)Sex3691218 M 0.0 0.0 0.0 Control F 0.0 0.0 0.0 oo oo 0.0 0.0 M 0. 2 100 0.0 0.0 0.0 F 0.0 0.0 0.0 0.0 0.0 o 24 0.0 0.0 0.0 PO W TOXSTUDIES1549 U n lu lb u a l B I O T E S T labyuiiosiiei., Stic. Dietary Level (opm) Control Sex M F 3 38 33 100 M 33 F 29 TABLE VUI TEST MATERIAL: Aroclor 1260 Two-Year Chronic Oral Toxicity Study - Albino Rats Clinical Blood Chemistry Data Summary of Mean Values Serum Glutamic-Pyruvic Transaminase Activity {Dade Units) Month: 6 9 12 18 24 36 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 pj TOXSTUDIES1550 t% viiilV ual b I U I ^ I Xa&yM&xuei, Dietary Level (ppm) Control Sex M F 3 128 130 M 118 100 F 117 TABLE IX TEST MATERIAL: Aroclor 1260 Two-Year Chronic Oral Toxicity Study - Albino Rats Clinical Blood Chemistry Data Summary of Mean Values Fasted Blood Glucose Concentration (mgs%) Month: 6 9 12 18 123 89 88 138 118 115 92 134 24 99 109 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 18.9 17. 8 10.6 11.9 16. 8 20. 2 118 116 135 146 98 116 115 138 146 94 37.8 12.0 21. 8 12. 1 21.9 7.6 23.9 11.7 11.9 7.8 16. 1 12.4 a<O-' tVSii A 9t0 TOXSTUDIES1551 ?4idiiilAial B I O - 1 fc b 1 Xaiwatosuci, `Jnc. 26 E. Urine Analyses Mean male and female urine analyses data are summarized in Tables X through XII. 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 the intervals of examination. 0J6t>6<*6 TOXSTUDIES1552 Dietary Level (ppm) Control Sex 3 Mn Fn Mn 100 Fn TABLE X TEST MATERIAL: Aroclor 1260 Two-Year Chronic Oral Toxicity Study - Albino Rats Urine Analyses Data Summary of Mean Values Glucose Month: 6 9 12 nnn nn n IB 24 nn nn Albumin Month: 3 6 9 12 nnt t nnnn n n n nn n n n nn nt t t n n, n n & 18 24 +2 +3 t +2 +1 +3 + 1 +4 O m </> Key: n = negative t = trace; less than 30 mg/100 ml urine + 1 = 30 to 100 mg/100 ml urine + 2 = 100 to 300 mg / 100 ml urine + 3 = 300 to 500 mg/100 ml urine + 4 = more than 500 mg/100 ml urine <0 6*6 - .. . - tv TOXSTUDIES1553 o Dietary Level (ppm) Sex 3 MN Control FN 100 MN FN TABLE XI ' TEST MATERIAL: Aroclor 1260 Two-Year Chronic Oral Toxicity Study - Albino Rats Urine Analyses Data Summary of Mean Values Microscopic Elements Month: 6 9 12 18 NN NN NNNt 24 +1 t pH Month 3 6 9 12 18 24 776 776 8 87 86 6 N N N Nt N N N tt 7 7 6 76 6 7 -8 6 7 6 6 Key: Normal t = trace; less than 5 per low power field + 1 = 5 to 10 per low power field + 2 = 10 to 15 per low power field + 3 = more than 15 per low power field , * CD TOXSTUDIES1554 jKdHitniai P I U M t J O Dietary Level (ppm) Control 100 Sex M F M F o TABLE XU TEST MATERIAL: Aroclor 1260 Two-Year Chronic Oral Toxicity Study - Albino Rats Urine Analyses Data Summary of Mean Values . 3 1.029 1.020 6 1.022 1.019 Specific Gravity Month: 9 12 1.033 1.027 1.025 1.024 18 1.042 1.032 1.021 . 1.016 1.025 1.023 1.031 1.035 ' 1.030 1.029 1.043 1.028 s 24 1.051 1.039 1.039 ` 1.045 bbW tO TOXSTUDIES1555 SnJuitual B I O - T E S T lakviatyuei., 9nc> 30 F. Pathologic Studies 1. Three-Month Sacrifice a. Gross Pathologic Findings No outstanding differences were noted between test and control rats upon gross pathological examination. 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 XIII through XVIII. 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. 0365700 TOXSTUDIES1556 Sndt't'U'Ual B I O - T E 5 T Dietary Level of Aroclor 1260 (ppm) Control 1 10 100 OQ TABLE XIII 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: 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 4. 13 4. 16 3. 90 4. 59 4.48 3.61 ' 5.73** 4.58 Organ/Brain Weight Ratio (g/g) Males Females 10.3 6.82 9.98 6.86 11.8 6.38 14.4** 7.72 ** Statistically significant diffe rence at the 99 percent confide nee level. Jt TOXSTUDIES1557 ZO Z^fO r \ i a tvnn>rpK o Dietary Level of Aroclor 1260 (ppm) Control i 10 100 o TABLE XIV TEST MATERIAL: AtocIot 1260 Two-Year Chronic Oral Toxicity Study - Albino Rats . Organ Weight and Ratio Data Three-Month Sacrifice Summary of Mean Values Organ: Kidneys Q 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 nfa TOXSTUDIES1558 Dietary Level of Aroclor 1260 Control 1 10 ioo o 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 Organ/Body Weight Ratio Organ/Brain Weight Ratio (g) (g/100 g) (g/g) Males Females___________ Males_______ Females___________ Males_______ Females 0.766 0.578 0. 150 0.184 0.371 0.302 0.846 0.516 0. 161 0. 180 . 0.412 0.269 0.838 0.718 0.632 0.556 0.156 0. 140 0.189 0.177 0.411 0.352 0.331 0.297 CD C v. K Owd TOXSTUDIES1559 *o*s9FO r \ i a ivmwpuK o Dietary Level of Aroclor 1260 (ppm) Control 1 10 100 o TABLE XVI 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: Gonads o . Organ Weight Organ/Body Weight Ratio Organ/Brain Weight Ratio (g) (g/100 g) <g/g) Males_______ FemalesMales_______ FemalesMalesFemales 3.60 0.114 0.698 0.0370 1.74 0.0599 3.67 0. 128 0.704 0.0450 1.80 0.0666 3.83 0.121 0.715 0.0368 1.89 0.0636 3.71 0.138 0.725 0.0429 1.81 0.0728 n o K I 4* k TOXSTUDIES1560 O Dietary Level of Aroclor 1260 (ppm) Control 1 10 100 o TABLE XVII 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: Heart o . Organ Weight (g) Males Females 1.59 1.05 1.57 1.01 1.52 1.04 0.946 Organ/Body Weight Ratio (g/100 g) Males_______ Females 0.307 0.300 0.339 0.353 0.296 0.298 0.311 0.297 Organ/Brain Weight Ratio (g/g) MalesFemales 0.767 0.551 0.765 0.526 0.781 0.743 0.546 0.505 u SO99tO 00 TOXSTUDIES1561 S 3 1 - O I 8l w tf O Dietary Level . of Aroclor 1260 (ppm) Control 1 10 100 O TABLE XVIII 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: Brain Organ Weight <g> Males Females 2.07 1.91 2.05 1.92 2.04 2.05 1.91 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 COO' TOXSTUDIES1562 $*iJuikial B I O - T E S T JafaMoiMiei, 2nc. 37 c. Histopathologic Findings Histopathologic examination of tissues and organs taken from all animals from both the control and 100 ppm groups was conducted. Tables XIX 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 Aroclor 1260. 03 70 7 TOXSTUDIES1563 Sndustnial b I U - I fc 2 I Jlafoyial&Uci, 38 TABLE XIX TEST MATERIAL: Aroclor 1260 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 Ave rage Incidence G rade 1 1.0 1 1.0 3 1.0 1 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 .' 036570b TOXSTUDIES1564 Mutual B I O - 1 fc b I Xabyiatviici, 'Jnc. 39 TABLE XX TEST MATERIAL: Aroclor 1260 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 Lung Trache itis 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 1.0 2 1.0 1 1.0 All other tissues and organs were normal histologically. Grading System 0.5= minimal 1.0 = slight 2.0 = mild 3.0 = mode rate 4.0= severe 5.0 = extreme ' O cnt>s ?o^ TOXSTUDIES1565 'JndulViial b I U I t i I JlalMyi&i&uci, !/nc. 40 2, Six-Month Sacrifice a. Gross Pathologic Findings No outstanding differences were 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 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, O 0365710 TOXSTUDIES1566 o 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 Dietary Level of Aroclor 1260 Organ Weight (g) Organ/Body Weight Ratio (g/100 g) Organ/Brain Weight Ratio (g/g) (ppm)Males_______ FemalesMales_______ FemalesMale 3______ Female b Control 22.9 13. 1 3.74 3.77 11.7 6.71 1 14.8** 15.1 2.92** 3.74 7.05** 7.86 10 19.0** 10.5** 3.31* 3.08* 9.45* 6.07 100 24.4 11.6 4.69* 4.03 12.3 6. 17 * Statistically significant difference at the 95 percent confidence level. ** Statistically significant difference at the 99 percent confidence level. v C rt Kf l 03657U 'K TOXSTUDIES1567 P tid/tihial B I O T E S T XabototvU&i, Una. Jo TABLE XXII 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: Kidneys Dietary Level Organ Weight Organ/Body Weight Ratio Organ/Brain Weight Ratio Aroclor 1260 (g) (g/100 g) (g/g) (ppm)Males_______ FemalesMales_______ FemalesMales_______ Females Control 4.04 2.79 0.664 0.806 2.06 1.43 1 3.64 2.73 0.716 0.674* 1.73 1.42 10 3.85 2.35 0.670 0.684* 1.92 1.36 100 3.92 2.35 0.753 0.814 1.97 1.25 * Statistically significant difference at the 95 percent confidence level. t-j ? , 'f S9C0 TOXSTUDIES1568 o Dietary Level of Aroclor 1260 (ppm) Control 1 10 100 o TABLE XXm 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: Spleen o * 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 Organ/Brain Weight Ratio (g/g) Males Females 0.384 0.350 0.359 0.472 0.416 0.327 0.320 0.236* * Statistically significant difference at the 95 percent confidence level. f 1/M CO TOXSTUDIES1569 o Dietary Level of Aroclor 1260 (ppm) Control 1 10 100 o TABLE XXIV 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: 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 0.62 0 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. TOXSTUDIES1570 S U S IE O 'i&n<nm-ofn>T i c a I - Qo TABLE XXV 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: Heart " Dietary Level of Aroclor 1260 Organ Weight (g) Organ/Body Weight Ratio (g/100 g) Organ/Brain Weight Ratio (g/g) (ppm)Males_______ FemalesMales_______ FemalesMales_______ Females Control 1.70 1.05 0.282 0.302 0.867 0.538 1 1.45 1.12 0.286 0.277 0.690 0.583 10 1.63 1.05 0.283 0.307 0.810 0.606 ICO 1.49 1.06 0.286 0.368** 0.749 0.564 ** Statistically significant difference at the 99 percent confidence level. TOXSTUDIES1571 Q Dietary Level of Aroclor 1260 (ppm) Control 1 10 100 TABLE XXVI 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: Brain Organ Weight <g) Males Females 1.96 1.95 2.10 2.01 1.92 1.73 1.99 1.88 Organ/Body Weight Ratio (g/100 g) Males Females ( ' 0.320 0.560 t 0.412* 0.474* 0.349 0.504 0.382 0.650* Final Body Weights of Sacrificed Rats (g) Males Females 613 348 509 405 575 . 343 522 289 * Statistically significant difference at the 95 percent confidence level. ci*> O TOXSTUDIES1572 Sitftait'ual B I O - T E 5 T labtyxtib'U&s., 9ac. 47 O c. Histopathologic Findings ' Histopathologic examination of tissues and organs taken from all animals from both the control and 100 ppm groups was conducted. ` 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 036&717 TOXSTUDIES1573 $*diVual B I O - T E S T labwatjyuM, Vue. 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 Hype remia Focal pericholangitis Focal inflammation 2 2 1 2 I 1 1.5 1.0 0.5 1.0 1.0 1.0 5 Females T rachea Lung Liver Kidney Focal tracheitis Hyperemia Hyperemia 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= minimal 1.0 = slight 2.0 =' mild 3.0= mode rate 4.0= severe 5.0 = extreme -' O 0365710 TOXSTUDIES1574 I XQWUUMiCi-, JtiC. TABLE XXVIII TEST MATERIAL: Aroclor 1260 Two-Year Chronic Oral Toxicity Study - Albino Rats Histopathologic Changes Six-Month Sacrifice Group: 100 ppm . Number of Animals Organ Examined Findings Ave rage Incidence Grade 5 Males Trachea Lung Liver Tracheitis Focal tracheitis Focal pneumonitis Hyperemia Hyperemia Focal pericholangitis 2 1 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 2 1 2 1 3 0.5 1.0 3.0 1.5 0.5 0.5 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 0 365 7L9 TOXSTUDIES1575 ' ytutaiiMal B I O - T E S T Ja&Mafotiei, 9+ic. 50 ^ 3. Twelve-Month 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 twelve month sacrifice are presented in Tables XXIX through XXXIV. 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 Aroclor 1260. 0365720 TOXSTUDIES1576 o Dietary Level (ppm) Control 1 10 100 oo TABLE XXIX 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: Liver Organ Weight (g) Males Females 22. 1 15.5 17.1* 10.7* 20.0 13.6 28.8* 14. 1 Organ/Body Weight Ratio Cg/100 g) Males Females 3.79 3.52 2.79** 3.01* 3.30 3.54 4.26 3.79 Organ/Brain Weight Ratio (g/g) Males Females 10.8 7. 72 9.23 5.76 10.8 7.28 13.4* 8.52 * Statistically significant diffe rence at the 95 percent confidence level. ** Statistically significant diffe rence at the 99 percent confidence level. T22S9FO TOXSTUDIES1577 Dietary Level (pom) Control 1 10 100 o TABLE XXX 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: Kidneys Organ Weight (g) Males F emales Organ/Body Weight Ratio (g/100 g) Males Females 4.04 3.84 4.00 5.11* 3. 19 2.58** 2.78* 2.81 0.692 0.625 0.660 0.758 0.738 0.724 0.736 0.755 Organ/Brain Weight Ratio (g/g) Males Females 1.97 1.58 2.06 1.39 . 2. 16 1.48 2.38* 1.69 .* `S c ^ ^ c | > * Statistically significant difference at the 95 percent confidence level. ** Statistically significant difference at the 99 percent confidence level. TOXSTUDIES1578  TABLE XXXI 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: Spleen Organ Weight Organ/Body Weight Ratio Organ/Brain Weight Ratio Dietary Level (g) (g/100 g) (g/g) (ppm)MalesFemalesMalesFemalesMalesFemales Control 1 0.778 0.756 0.796 0.460* 0.133 0.122 0. 183 0.129* 0. 380 0.408 0.396 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. TOXSTUDIES1579 O 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 Organ/Body Weight Ratio Organ/Brain Weight Ratio Dietary Level (g) (g/lOOg) (g/g) (ppm)MalesFemalesMalesFemalesMalesFemales Control 3.46 0. 116 0.596 0.0275 1.70 0.0574 1 3.38 0. 103 0. 551 0.0287 1.82 0.0552 10 3.51 0.112 0.578 0.0294 - 1.89 0.0584 100 4.03** 0.088* 0.598 0.0238 1.88 0.0527 * Statistically significant difference at the 95 percent confidence level. ** Statistically significant difference at the 99 percent confidence level. *2*S9C0 TOXSTUDIES1580 o ! Dietary Level (ppm) Control 1 10 100 o TABLE XXXIII 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: Heart Organ Weight (g) . Males Females 1.71 1.23 1.68 1.07 1.59 1.16 1.86 1.27 Organ/Body Weight Ratio (g/100 g) Males Females 0.293 0.287 0.273 0.301 0.261 0.307 0.275 0.340 Organ/Brain Weight Ratio (g/g) Males Females 0.835 0.611 0.902 0.575 0.845 0.620 0.868 0.760 TOXSTUDIES1581 $w tutfrtal B I O - T EST lal& m iM tei, 9ac, o oo Dietary Level (opm) Control 1 10 100 TABLE XXXIV TEST MATERIAL: Aroclor 1260 Two-Year Chronic Oral Toxicity Study - Albino Rats Organ Weight and Ratio Data Twelve-Month Sacrifice Summary of Mean Values Organ Weight Males (g) Females Organ: Brain Organ/Body Weight Ratio Cg/ 100 g) Males Females Final Body Weight of Sacrificed Rats (grams) Males Females 2.04 2.02 0.349 0.460 584 439 1.87 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. yOi' TOXSTUDIES1582 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. 0365727 TOXSTUDIES1583 90 TABLE XXXV TEST MATERIAL: Aroclor 1260 Two-Year Chronic Oral Toxicity Study - Albino Rats Histopathologic Changes Twelve-Month Sacrifice Croup: Control . Number of Animals_______ Organ ExaminedFindingsIncidence Average Grade 5 Males Trachea Lung Urinary Bladder Tracheitis Chronic respiratory disease Calculus 1 2 1 1.0 1.0 1.0 5 Females Trachea Lung Colon Tracheitis Chronic respiratory disease Paras ites L 1 1- 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 = moderate 4.0= severe 5.0 = extreme 0365728 TOXSTUDIES1584 Jrtduihiai B I O T S T laJiMai&xi&i, ov O TABLE XXXVI TEST MATERIAL: Aroclor 1260 Two-Year Chronic Oral Toxicity Study - Albino Rats Histopathologic Changes Twelve-Month Sacrifice Group: 100 ppm Number of Animals 5 Males 5 Females Organ Examined Trachea Lung Kidney Liver Trachea Lung Findings Incidence Ave rage Grade Tracheitis Chronic respiratory disease Focal lymphoid infiltration Vacuolar change of random cells 1 3 1 1 1.0 1.0 1.0 1.0 Tracheitis Chronic respiratory disease 1 1 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* moderate 4.0= severe 5.0 = extreme . . 9 0365729 TOXSTUDIES1585 BIO"TE5T Jlobyiat&ii&L, 9nc. 60 Q 4. Final Sacrifice a. Cross 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 Aroclor 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 Aroclor 1260 , O 0365730 TOXSTUDIES1586 'wW p V I S 3 1 - 0 1 9 1" r* P y p '(- o Dietary Level (ppm) Control 1 10 100 TABLE XXXVII ` TEST MATERIAL: Aroclor 1260 Two-Year Chronic Oral Toxicity Study - Albino Rats Organ Weight and Ratio Data Summary of Mean Values Final Sacrifice -------- - - ... Organ Weight Males (g) Females 22. 0 16. 3 Organ: Liver --- Organ/Body Weight Ratio (g/lOOg) 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 95 percent confidence level. * Statistically significant difference at the 99 percent confidence level. o - _y Organ/Brain Weight Ratio (g/g) Males Females 10. 10 '8.42 9-93 8.62 11. 20 9. 26 13.40* 11.60* TOXSTUDIES1587 Dietary Level (ppm) Control 1 10' 100 TABLE XXXIX TEST MATERIAL: Aroclor 1260 Two-Year Chronic Oral Toxicity Study - Albino Eats Organ Weight and Ratio Data Summary of Mean Values Final Sacrifice ' Organ Weight Males (g) Females Organ: Spleen Organ/Body Wei ght Ratio (g/100 g) Males Females 1. 15 0. 96 0. 182 0. 181 1. 17 0. 72 0. 178 0. 148 1.09 0. 89 0. 83 0. 75 0. 131 0. 138 0. 142 0. 146 Organ/B rain Weight Ratio (g/g) Males Females 0. 520 0.492 0. 529 0. 370 0. 509 0. 428 0.400 0. 379 c2 -- i t TOXSTUDIES1588 90 Dietary Level _____ (PPrri)__________ Control 1 10 100 - TABLE XL TEST MATERIAL: Aroclor 1260 Two-Year Chronic Oral Toxicity Study - Albino Rats . Organ Weight and Ratio Data Summary of Mean Values Org an Weight Males <g) 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 Q Organ/Brain Weight Ratio Males (g/g) Females 1. 15 0.0628 1.61* 0.-0718 1. 56* 0.0900 1. 33 0.0584 * Statistically significant difference at the 96 percent confidence level. cU1 TOXSTUDIES1589 o Dietary Level (ppm) Control I 10 100 TABLE XLI TEST MATERIAL: Aroclor 1260 Two-Year Chronic Oral Toxicity Study - Albino Rata Organ Weight and Ratio Data i Summary of Mean Values Final Sacrifice Organ: Heart Organ Weight <s> Males Females 1.87 1.54 1.98 1.45 Organ/Body Weight Ratio (g/100 g) Males Females 0.294 0. 288 0. 304 0. 294 1. 90 1. 58 0.225** 0.279 2.00 1.49 0. 313 0. 288 * Statistically significant difference at the 99 percent confidence level. Q $ l Organ/Brain Weight Ratio Males (g/g> Females 0. 860 0. 795 0.893 0.747 0.884 0.809 0.904 0.764 c V TOXSTUDIES1590 f liu b t lt iL il B I O T E S T XaiuyuiianicA, 2* 036573 o o Dietary Level (ppm) Control 1 10 100 TABLE XLII TEST MATERIAL: Aroclor 1260 Two-Year Chronic Oral Toxicity Study - Albino Rata * ' . Organ Weight and Ratio Data i Summary of Mean Values Final Sacrifice ' Organ: Brain Organ Weight Males (g> Females Organ/Body Weight Ratio (g/100 g) Males Female Final Body Weight of Sacrificed Animals (grams) Males Females 2. 18 2.21 2. 15 2. 22 1.95 1.94 1. 96 1.95 0. 342 0. 343 0.255** 0. 346 0. 362 0.407 0. 347 0. 378 642 654 . 845** 641 551 525 584 644 ** Statistically significant difference at the 99 percent confidence level. TOXSTUDIES1591 9nduitual B I O T E 5 T iwiQuy'Uei-, $nc. 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 XL>VI 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 -1 (1 ppm) 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 0365736 TOXSTUDIES1592 9nduiifUal B I O T E 5 T Jtahvurio-'iiei, 9nc. 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-I and 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. Gordon, D. V. M. , Ph. D. Diplomate, American College of Veterinary Pathologists 0365737 TOXSTUDIES1593 oo TABLE XLHI TEST MATERIAL: Aroclor 1260 Two-Year Chronic Oral Toxicity Study - Albino Rata Histopathologic Changes Final Sacrifice Group: Control Number of AnimalsOrgan ExaminedFindings IncidenceGrade 11 Males Heart Trachea Lung Liver Stomach Spleen Kidney Testes ' ' Prostate Adrenal Gland Brain Eye 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 3 3 9 1* 2 1 3 3 2 2 1 1 1 1 1 .2 O i ! ( Average f 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 f o a f4 S Q C 0 TOXSTUDIES1594 B I O - T ES T JaA&uziniesi, OO TABLE XLIII continued TEST MATERIAL: Aroclor 1260 Two-Year Chronic Oral Toxicity Study - Albino Rats Histopathologic Changes Final Sacrifice Group: Control Number of Animals Organ Examined Findings Incidence 14 Females 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 organs were normal histologically. Grading System ' ' 0. 5 = minimal 2.0= mild 4. 0 = severe 1.0 = slight 3.0 = moderate 5. 0 = extreme 7 9 13 3 2 1 2 3 5 1 4 3 6 1 1 9 4 1 Average ___ Grade__ 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 TOXSTUDIES1595 e Number of Animals 11 Males o uJ o TABLE XLIY TEST MATERIAL: Aroclor 1260 Two-Year Chronic Oral Toxicity Study - Albino Rats Histopathologic Changes Final Sacrifice Group: 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 Z 4 1 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 TOXSTUDIES1596 QO Number of Animals 11 Males TABLE XLIV continued TEST MATERIAL: Aroclor 1260 Two-Year Chronic Oral Toxicity Study - Albino Rats 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 Chronic focal myocarditis Chronic focal myocarditis Tracheitis Chronic respiratory disease Focal fibrosis Focal lymphoid infiltration Ductile hyperplasia Congestion Vacuolar change (fatty) Chronic gastritis Acanthosis v 3 1 9 13 1 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 0 3 6 b ?*! TOXSTUDIES1597 Number of Animals 14 Females TABLE XLIV continued TEST MATERIAL: Aroclor 1260 Two-Year Chronic Oral Toxicity Study - Albino Rats Histopathologic Changes Final Sacrifice Group: 1 ppm Organ ExaminedFindingsIncidence Stomach Colon Spleen Lymph Node Kidney Uterus Adrenal Gland Ulceration and acanthosis Parasites Hemosiderosis Hyperplasia Congestion Chronic nephritis Vacuolar change (fatty) Metritis Telangiectasis Nodular hyperplasia Congestion 1 1 11 1 1 3 1 4 9 3 1 Q . \ ': , * ' , Average Grade 1.0 1.0 1.0 1.0 1.0 2.0 1. 0 1. 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 TOXSTUDIES1598  Number of Animals 7 Males TAB LE XLV TEST MATERIAL: Aroclor 1260 Two-Year Chronic Oral Toxicity Study - Albino Rats 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 Heart Trachea Lung Chronic focal myocarditis Thracheitits Chronic respiratory disease 3 8 24 Average Grade 1.0 1.0 1. 0 3. 0 1.0 1.0 l.o 1.0 1.0 1.0 1.0 . 1.0 1.0 1.0 * 0f TOXSTUDIES1599 o TABLE XLV continued & TEST MATERIAL: Aroclor 1260 Two-Year Chronic Oral Toxicity Study - Albino Rata cc C Histopathologic Changes Final Sacrifice Group: 10 ppm ' Number of AnimalsOrgan ExaminedFindings - Average IncidenceGrade 14 Females Liver Pancreas Stomach Spleen Kidney Uterus Pituitary Adrenal Gland Vacuolar change (fatty) Focal hyperplasia Chronic focal pancreatitis Periarteritis Acanthosis Hemosiderosis Chronic nephritis Metritis Congestion Telangiectasis Nodular hyperplasia Congestion 1 1. 0 1 1. 0 3. 0 1 3.0 1 1.0 12 1.0 10 1.0 7 2. 0 1 1. 0 7 1.0 1 1.0 1 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 ' ui TOXSTUDIES1600 Oo TABLE XLVI TEST MATERIAL: Aroclor 1260 Two-Year Chronic Oral Toxicity Study - Albino Rats Histopathologic Changes Final Sacrifice Group: 100 ppm Number of AnimalsOrgan ExaminedFindingsIncidence 10 Males Heart Trachea Lung Liver Pancreas Stomach Spleen Kidney Chronic focal myocarditis Tracheitis Chronic respiratory disease Congestion Vacuolar change (fatty) Focal degeneration Congestion Centrolobular hypertrophy Telangiectasis Chronic focal pancreatitis Inflammation Acanthosis Hemosiderosis Focal lymphoid infiltration Calcified concretions in pelvis 5 8 9 1 2 1 3 .2 1 2 2 2 7 1 1 Q Average Grade 1.0 1.0 2.0 1.0 2.0 1.0 2.0 I. 0 1.0 1.0 2.0 1. 0 1.0 1.0 1. 0 1. 0 SVZ.99E0 TOXSTUDIES1601 oo Number of Animals 10 Males TABLE XLVI continued TEST MATERIAL: Aroclor 1260 Two-Year Chronic Oral Toxicity Study - Albino Rats Histopathologic Changes Final Sacrifice Group: 100 ppm* Organ Examined Kidney (continued) Testes Prostate Thymus . Adrenal Gland Findings Calcified concretions in pelvis Aspermia Inflammation Cyst Telangiectasis Nodular hyperplasia Incidence 1 1 1 13 1 15 Females Heart Trachea Lung Liver Chronic focal myocarditis Tracheitis Chronic respiratory disease Congestion Edema Vacuolar change (fatty) . 5 8 11 1 1 5 Q V j s Average Grade 1.0 1.0 1.0 1.0 1.0 1. 0 0 0 0 0 0 0 -J -J TOXSTUDIES1602 oo Number of Animals 15 Females s -J -J TABLE XLVI continued TEST MATERIAL: Aroclor 1260 Two-Year Chronic Oral Toxicity Study - Albino Rats Histopathologic Changes Final Sacrifice Group: 100 ppm* Organ Examined Liver (continued) Pancreas Spleen Kidney Ute rus 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 Hyi^crplasia 4 1 5 2, 1 1 9 8 7 1 6 1 1 1 All other tissues and organs were normal histologically. 0.5 = minimal Grading System 2.0 - mild 4.0 severe 'j '{ ' .* 1 ( ; 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 TOXSTUDIES1603 O Group C T-I (1 ppm) T-U (10 ppm) T-III {100 ppm) Sex M F M F M F M F Q TABLE XLVII TEST MATERIAL: Aroclor 1260 Two-Year Chronic Oral Toxicity Study - Albino Rats Histopathologic Changes of the Urinary Bladder Final Sacrifice Number Examined Findings* 11 Proteinaceous plug (34) 14 Focal epithelial hyperplasia (62) 10 Proteinaceous plug (86, 105, and 107) 11 None 7 Proteinaceous plug (187) 14 None 10 Proteinaceous plug (271) 14 None Incidence 1 1 3 - 1 - 1 * * Individual animal numbers are shown in parentheses. Grading System 1.0 = minimal or trace 4. 0 = severe 2.0 = mild 5.0 = extreme 3. 0 = moderate Average Grade 1.0 _ _ _ - TOXSTUDIES1604 yncutu/uai Di - I b J I j_ao&iuuyu&i., jrtc. "' G. Detailed Description of Tumor Findings Tumor data for individual animals including location, weight and pathologic classification arc 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. 0 TOXSTUDIES1605 o Animal 'Cumber and Sex 1-M 2-M ' 46-F Location Abdomen Pancreas Abdomen 47-F . 43-F 50-F 52-F 59-F ] 64-F 66-F o o5 o Lymph node Abdomen Abdomen Abdomen Abdomen Adrenal gland Abdomen Abdomen G TABLE XL VIII ' TEST MATERIAL: Aroclor 1260 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 - _, 13x11x4 13,x 11 x,4 Classification Mammary fibroadenoma Adenocarcinoma Mammary fibroadenoma Mammary fibroadenoma . Reticulum cell sarcoma Mammary fibroadenoma Mammary fibroadenoma Mammary fibroadenoma Mammary fibroadenoma Pheochromocytoma Fibroadenoma Mammary adenoma Months on Test 24 24 24 24 24 7 24 24 24 . 24 | i ! c TOXSTUDIES1606 o Animal Number and Sex 99 - M 127-F 128-F 138-F 141 -F 151 -F 152-F u> IT U' Location Pituitary Pituitary Abdomen Pituitary Abdomen Abdomen Pituitary Ovary Abdomen Abdomen o TABLE XLIX TEST MATERIAL: Aroclor 1260 Two-Year Chronic Oral Toxicity Study - Albino Rats Description of Tumor Findings Group: 1 ppm Weight (grams) - 25.00 . 60. 20. 07 14. 89 540.00 Size (cm) - 6x3x1 5x6x2 - 13x15x2 Cla s sification ^Chromophobe adenoma L Chromophobe adenoma L Mammary fibroadenoma ^Chromophobe adenoma ^ Mammary fibroadenoma i' .< * Mammary fibroadenoma i Chromophobe adenoma Adenoma Mammary fibroadenoma Mammary fibroadenoma Months on Te st 20 24 21 24 24 24 22 TOXSTUDIES1607 oo Animal Number and Sex 205-F 208-F 213-F 216-F 220-F 221-F TABLE L TEST MATERIAL: Aroclor 1260 Two-Year Chronic Oral Toxicity Study - Albino Rats Description of Tumor Findings Group: 10 ppm Location Abdomen Pituitary Abdomen Right shoulder Abdomen Pituitary Submaxillary region Abdomen Weight (grams) 190.00 138.00 9. 57 - 14.44 29.0 Size (cm) 9x5x4 _ " 2x3x1 3x5x2 Classification u' Mammary fibroadenoma i-Chromophobe adenoma t Mammary fibroadenoma , ^ Subcutaneous tumor '-"Mammary fibroadenoma / Chomophobe adenoma i Fibroadenoma i Mammary fibroadenoma o O' o Months on Test 24 24 24 23 24 24 TOXSTUDIES1608 e Animal Numb e r and Sex 22-F 233-F 234-F Location Left femoral region Pituitary Abdomen Pane reas o TABLE L continued TEST MATERIAL: Aroclor 1260 Two-Year Chronic Oral Toxicity Study - Albino Rata Description of Tumor Findings Group: 10 ppm Weight (grams) 56. 00 Size (cm) 6x8x2 Classification l/Subcutaneous tumor 60. 82 6x4x3 Chromophobe adenoma ^ Mammary fibroadenoma ^Tslet cell adenoma 9 i '5 ! t * Months on Test 6 24 24 TOXSTUDIES1609 Q Animal Number and Sex 2-14-M 264-M 281-F 293-F 294-F - 301^F: Location Pancreas Pancreas Abdomen Liver Abdominal cavity Liver T) TABLE LI TEST MATERIAL: Aroclor 1260 Two-Year-Chronic Oral Toxicity Study - Albino Rats Description of Tumor Findings Group: 100 ppm Weight (grams) 35. 04 50.75 Size (cm) '- 6x4x2 6x4x3 Classification i Adenoma ^Islet cell adenoma l/'Mammary fibroadenoma j Lympho s a rc om a ^ Fibroma - - Lymphosarcoma Months on Test 24 21 24 23 24 23 TOXSTUDIES1610 ' * Animal Number and Sex 302-F 308-F 311 -F 312-M 314-F Location Lymph node Pituitary Abdomen 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 Clas sification '/ Lymphosarcoma yy Chromophobe adenoma 41ammary fibroadenoma , tMammary fibroadenoma ^^Chromophobe adenoma ^ Mammary fibroadenoma ? i j > Months on Test 24 24 24 24 24 o u* O' O' si O' TOXSTUDIES1611