Document Ne5LYObLLvxVy4ENkRvqOVrJV

OrvSuibu/jJ, BIO - T E S T JlGJyyiahyiieA, Snc. 1S10 FRONTAGE ROAD NORTHBROOK. ILLINOIS 60062 November 12, 1971 1 Mr. Elmer P. Wheeler Monsanto Company 800 North Lindbergh Boulevard St. Louis. Missouri 63166 Dear Mr. Wheeler: Re: IBT 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 HONS 068401 PROJECT NO'./-. 1 HEPORT FILE ------- ' StvSu&friUjJ, BIO -TEST JPcJyyujJ&ueA. Snc. 1B10 FRONTAGE ROAD NORTHBROOK. ILLINOIS 6006S REPORT TO MONSANTO COMPLY TWO-YEAR CHRONIC ORAL TOXICITY WITH AROCLOR 1260 O' IN ALBINO RATS NOVEMBER 12, 1971 ,' {' i EBT NO. B7298 HOMS 068402 LtUxid. . B 1 O T E S T JaiaiaJMiM, Jkc. REPORT TO MONSANTO COMPANY TWO-YEAR CHRONIC ORAL TOXICITY WITH AROCLOR 1260 IN ALBINO RATS NOVEMBER 12, 1971 IBT NO. B7298 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. MCNS 068403 }mbiiUial BIO-TEST JaitnaivUM, 9m 2 U. 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-UI 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. MONS 068404 J.uLiittial B I O T E S T Jaia^aiyuei, Unc. 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: Philip Si mith, B. S. Assistant Toxicologist Rat Toxicity Report approved by: James B. Plank Semor Group Leader Rat Toxicity -jZ/jJ Paul L. Wright, Pn. D. Section Head, Toxicology Manager, Toxicology November 12, 1971 lam:sjn KONS 068405 ' ' B I O - T E S T la&yiai&utbi. Una. 4 Q Q III. Procedure A. Experimental Animals The animals 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 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: Aroclor 1260 Two-Year Chronic Oral Toxicity Study - Albino Rats Outline of Experiment Group Number of Animals Male Female Dietary Level (ppm) Control 50 50 None Administered T-I 50 50 i T-II T-III 50 50 50 50 10 100 Charles River Breeding Laboratories, North Wilmington, Mass. HONS 068406 V-j'.r'B l O - T E 5 T $**c. 5 9 Q 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 ' ;. _ 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. MGNS 068407 ImLnl'Mll B I O - T E S T JaiacalyUct, }nc 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. O, 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. HONS 068408 iu-.l 0 I O - T E 5 T ^aJuviaioiia*., $**& 7 o o o 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 "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 1Z 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. Hie absolute weights of the liver, kidneys, spleen, gonads, heart and brain were recorded immediately after sacrifice. HONS 068409 Snduitual B I O - T E S T lahyiatsvucA, 2nc. 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. |. 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. HONS 068410 Undmi/ual B i 0 - T E S T 2alxt*aiva*i, }ne. 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 064U eo TABLE II TEST MATERIAL: Aroclor 1260 Two-Tear Chronic Oral Toxicity Study - Albino Rata Body Weight and Total Weight Gain Data Summary of Mean Values lietary Level of Aroclor 1260 (ppm) Sex Body Weight 90-Day . (grams) Total Weight Week: Gain 0 1 2 3 4 5 6 7 8 9 10 11 12 13 (erams/rat) Control i 10 100 M 133 203 245 313 362 373 391 409 424 440 440 449 467 474 F 136 178 190 219 244 254 259 265 270 276 281 278 290 288 M 133 192 250 322 361 374 394 416 428 448 450 474 479 490 F ' 136 167 189 218 241 252 256 261 268 273 277 281 290 288 M 133 204 245 317 368 382 400 417 436 448 461 467 475 481 F 136 174 190 217 242 254 260 263 268 274 281 279 285 288 M 133 208 247 319 363 375 394 425 437 451 460 479 486 500 F 136 173 188 222 240 253 258 262 265 267 270 275 275 280 341 152 357 152 348 152 367 144  Dietary Level of Aroclor 1260 (ppm) Sex Control M F iM F 10 M F 100 M F 9 TABLE tl 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 (grams/rat) 701 568 390 254 699 ' 379 566 243 709 576 388 252 717 584 363 227 x 6 l/i O0" a> + Dietary Level of Aroclor 1260 (ppm) Sex Control M F iM F 10 M F 100 M F oo TABLE n continued TEST MATERIAL: Aroclor 1260 Two-Year Chronic Oral Toxicity Study - Albino Rata Body Weight and Total Weight Gain Data Summary of Mean Values 13 14 15 16 Bod/ Weight 24-Month (grams) Total Weight Month: Gain 17 18 19 20 21 22 23 24 (grams/rat) 728 746 759 768 769 767 760 758 739 726 687 642 426 444 466 481 500 515 533 547 551 550 564 551 721 740 760 768 776 774 762 753 733 718 715 654 390 427 466 433 445 476 481 493 514 530 484 525 509 415 521 385 728 745 776 761 768 780 774 761 735 715 683 645 416 434 482 449 473 508 519 530 536 542 536 584 746 760 772 775 774 769 760 750 733 714 711 641 380 386 417 414 435 453 471 481 500 507 485 537 512 448 508 401 (*o/) o ft) * inJuibuol B I O * T E S T JaUwilyuM, 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. *CNS 068*15 0oo AB I O - T E S T TABLE in TEST MATERIAL: Aroclor 1260 Two-Year Chronic Oral Toxicity Study - Albino Rata Food Consumption Data Summary of Mean Values* Food Consumption dietary Level of (grams/rat/seven days) Average Food jt Aroclor 1260 Week: Consumption ^ (ppm) Sex 1 2 3 4 5 6 7 8 9 10 11 12 13 (grams/rat/seven davsF 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 90 190 167 155 151 150 149 152 100 M 121 150 156 117 187 124 121 190 196 186 184 199 189 F 89 93 123 151 151 101 193 136 140 144 144 147 146 175 143 163 135 c TIn O Oe>' *- O' o $Hduifaal B I O T E S T M 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 m c ontinued TEST MATERIAL: Aroclor 1260 Two-Year Chronic Oral Toxicity Study - Albino Rats 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) 189 168 147 163 184 179 170 187 154 136 121 138 152 160 141 127 176 142 200 189 192 179 181 182 172 184 163 141 163 160 153 157 143 132 186 151 191 188 193 197 197 168 164 196 138 145 144 144 151 136 139 141 186 142 170 180 188 186 166 181 188 180 127 147 144 134 132 162 149 139 ' 180 143 e* 2 C a a> * r SnduitniaL BIO-TEST JahyiaiosUeA. Jne. 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. ) HONS 068418 O Dietary Level (ppm) Sex Control M F iM 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 76 000 1 3 5 7 00 1 1 4 7 5 000 2 3 36 1 10 2 4 7 8 000 3 2 4 5 100 2 2 8 6 022 0 3 5 7 22-24 9 3 8 5 6 3 9 4 CJ O m 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. &1VB90 SNOW -j jtuLuinial B I O - T E S T Johvtaivuei, )nc. 18 0, 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. HONS 068420 V S 3 1 0 1 8 vt f 'T '6Tl 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 Rata Hematologic Data Summary of Mean Values Total Leukocyte Count (thousands/mm^) Month: 6 9 12 18 24 Erythrocyte Count (millions/mm^) ' Month: 36 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 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 O' 00 x oIzn I V i S3 i * O 19 / * W Dietary Level (ppm) Sex 3 M 17. 1 Control F 16.9 o 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 12 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 o 18 24 41 35 42 38 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 38 48 47 41 44 39 32 CooD> KK*jj O oo o tH I U I > I Dietary Level (ppm) Sex 3 M 82.0 Control F 83.0 TABLE VII TEST MATERIAL: Aroclor 1260 Two-Year Chronic Oral Toxicity Study - Albino Rata Hematologic Data Summary of Mean Valuea Differential Leukocyte Count (Number of Celia per Hundred) Lymphocytes Neutrophila 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 if 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 ial BIO -TEST lc 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 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 CO o 0.4 0.4 0.8 1.6 0.0 o 2 is> oO' O) K*j M * fyndailud B IO -T E S T 2c o Dietary Level (ppm)Sex Control M F M 100 F o TABUS 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) Basophils Month: 3 ___________ 6912_________ 1824 0.0 0.0 0. 0 0.0 0.0 0.0 0.0 0.0 0.0 0.0 0. 2 0.0 0.0 0.0 0.0 0.0 0.0 0.0 0.0 0.0 o 0.0 0.0 0.0 0.0 2e> Co acot wM K*j Ul y 1 s 3 o i a r w r ci DietaryLevel (ppm) Control Sex M F 3 38 33 M 33 100 F 29 TABLE VIII 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 ox I2/) e> o o> OK*-j I O l d Tm P 'PuZi Hm.vjmvWT I t t o Dietary Level (ppm) Control Sex M F 3 128 130 [ 100 M 118 F 117 TABLE IX TEST MATERIAL: Arodor 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 18 123 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 Nin fnduilUal B I O - 1 t i I XabanatMici, Vnc. 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. HONS 068428 BIO -TEST A Dietary Level (ppm) Control Sex M F 3 n n Mn 100 Fn TABLE X TEST MATERIAL: Arodor 1260 Two-Year Chronic Oral Toxicity Study - Albino Rats Urine Analyses Data Summary of Mean Values Glucose Month: 6 9 12 nnn nn a 18 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 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 HONS 0684^9 .. tsj o Dietary Level (ppm) Sex 3 MN Control FN MN 100 FN TABLE XI ' TEST MATERIAL: Aroclor 1260 Two-Year Chronic Oral Toxicity Study - Albino Rata Urine Analyses Data Summary of Mean Values Q Microscopic Elements Month: 6 9 12 18 NNNN NNNt 24 +1 t PH Month 3 6 9 12 18 24 7 76 7 7 6 88786 6 N N N Nt N N N tt 77676 6 7 867 6 6 Key: N- 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 HONS 068430 I jndatU ial B IO -T E S T J< N 00 vDi I c a 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 Rata 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 o K 24 1.051 1.039 1.039 ' 1.045 * ozu> Om' * Ii SnJttifatal B I O - T E S T Jal&ial&Uei, Hoc. 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. HONS 068432 CEV890 SNOW 1 S 3 1 O I fl T ^P 'T H o 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 *> ' Dietary Level . of Organ Weight Organ/Body Weight Ratio Organ/Brain Weight Ratio Aroclor 1260 (g) (g/100 g) (g/g) (ppm)MalesFemalesMales_______ FemalesMalesFemales Control 21.4 13.0 4.13 4. 16 10.3 6.82 1 20.4 13.2 3.90 4.59 9.98 6.86 10 24.0** 12.2 4.48 3.61 11.8 6.38 100 29.5** 14.5 5.73** 4.58 14.4** 7.72 ** Statistically significant difference at the 99 percent confidence level. t o oo TABLE XIV TEST MATERIAL: Aroclor 1260 Two-Year Chronic Oral Toxicity Study - Albino Rate Organ Weight and Ratio Data Three-Month Sacrifice Summary of Mean Values Organ: Kidneys Dietary Level of Organ Weight Aroclor 1260 (g) (ppm)Males_______ Females Control 4.03 2.49 i 4.37 2.62 10 4.00 2.61 100 4.00 2.52 Organ/Body Weight Ratio Organ/Brain Weight Ratio (g/100 g) (g/g) MalesFemalesMales_______ Females 0.782 0.802 1.95 1.31 0.838 0.911 2. 14 1.36 0.747 0.782 1.96 1.37 0.779 0.793 1.96 1.35 HONS o oo>* tJnLtihual B I O - T S 1 MCNS 0 6 8 4 3 5 o9 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 Dietary Level . of Organ Weight Organ/Body Weight Ratio Organ/Brain Weight Ratio Aroclor 1260 (g) (g/100 g) (g/g) (ppm)Males_______ FemalesMalesFemalesMalesFemales Control 0.766 0.578 0.150 0.184 0.371 0.302 1 0.846 0.516 0. 161 0. 180 0.412 0.269 10 0. 838 0.632 0.156 0.189 0.411 0.331 100 0.718 0.556 0. 140 0.177 0.352 0.297 If G Dietary Level of Aroclor 1260 (ppm) Control 1 10 100 G TABLE XVI TEST MATERIAL: Aroclor 1260 Two-Year Chronic Oral Toxicity Study - Albino Rati Organ Weight and Ratio Data Three-Month Sacrifice Summary of Mean Values Organ: Gonads O .. Organ Weight (g) Males Females 3.60 0. 114 3.67 0.128 3.83 0.121 3.71 0.138 Organ/Body Weight Ratio (g/100 g) Males Females 0.698 0.0370 0.704 0.0450 0.715 0.0368 0.725 0.0429 Organ/Brain Weight Ratio (g/g) Males Females 1.74 0.0599 1.80 0.0666 1.89 0.0636 1.81 0.0728 o O*D * r\ i a oo o TABLE XVII TEST MATERIAL: Aroclor 1260 Two-Year Chronic Oral Toxicity Study - Albino Rate Organ Weight and Ratio Data Three-Month Sacrifice Summary of Mean Values Organ: Heart Dietary Level of Organ Weight Organ/Body Weight Ratio Organ/Brain Weight Ratio Aroclor 1260 (g) (g/100 g) (g/g) (ppm)Male aFemalesMales_______ FemalesMalesFemales Control i 1.59 1.57 1.05 1.01 0.307 0.300 0.339 0.353 0.767 0.765 0.551 0.526 10 1.58 1.04 0.296 0.311 0.781 0.546 100 1.52 0.946 0.298 0.297 0.743 0.505 | v? HONS 0 6 8 4 3 7 cu o oo TABLE XVIII TEST MATERIAL: Arodor 1260 Two-Year Chronic Oral Toxicity Study - Albino Rats Organ Weight and Ratio Data Three-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_______ FemalesMalesFemales Control i 10 100 2.07 2.05 2.04 2.05 1.91 1.92 1.91 1.89 0.402 0.392 0.380 0.400 0.616 0.672 0. 572 0.593 518 314 523 287 536 337 517 321 tn O HONS 068438 O' Pmtuiiual B I O - T E S T 2aJ>&\alyiics, 9nc. 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. MGNS 068439 fnJitlUiai blU - I t> I JLaJxyial&uol, Vne. 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 Average 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 . AONS 0644q fnduihial B I O - I t b I XaAowivuci, 'Jrtc. 39 o 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 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 1.0 2 - 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 = mode rate 4.0= severe 5.0 = extreme ' <0 HONS 068441 9*duiVuai b I V I t 5 I Zai*&U2tVue4., Jnc. 40 o 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 o deleterious histopathologic change confirm that these differences were not related to the ingestion of Aroclor 1260. O HONS 06844^ o Dietary Level Aroclor 1260 (ppm) Control 1 10 100 o TABLE XXI TEST MATERIAL: Arodor 1260 Two-Year Chronic Oral Toxicity Study - Albino Rats Organ Weight and Ratio Data Six-Month Sacrifice Summary of Mean Values Organ: Liver o Organ Weight (g) Males Females 22.9 13.1 14.8** 15.1 19.0* 10.5** 24.4 11.6 Organ/Body Weight Ratio (g/100 g) Males Females 3.74 3.77 2.92** 3.74 3.31* 3.08* 4.69* 4.03 Organ/Brain Weight Ratio (g/g) Males Females 11.7 6.71 7.05** 7.86 9.45* 6.07 12.3 6. 17 * Statistically significant difference at the 95 percent confidence level. ** Statistically significant difference at the 99 percent confidence level. v C HONS 0 6 8 4 4 3 H I J . Dietary Level of Aroclor 1260 (ppm) Control i 10 100 o 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 Values Organ: Kidneys , o Organ Weight (g) Males Females 4.04 2.79 3.64 2.73 3.85 2.35 3.92 2.35 Organ/Body Weight Ratio (g/100 g) Males_______ Females 0.664 0.806 0.716 0.674*. 0.670 0.684* 0.753 0.814 Organ/Brain Weight Ratio (g/g) Males_______ Females 2.06 1.43 1.73 1.42 1.92 1.36 1.97 1.25 * Statistically significant difference at the 95 percent confidence level. HONS 0 6 8 4 4 4 t o oo 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 Organ Weight Organ/Body Weight Ratio Organ/Brain Weight Ratio Aroclor 1260 (g) (g/100 g) (g/g) (pom)Males_______ FemalesMales_______ FemalesMales______ Females Control 0.752 0.684 0.122 0.196 0. 384 0.350 1 0.754 0.908 0. 148** 0.220 0.359 0.472 10 0.836 0.566* 0. 146* 0.167 0.416 0.327 100 0.636 0.443* 0.122 0.151 0.320 0.236* HONS 0 6 8 4 4 5 * Statistically significant difference at the 95 percent confidence level. o Dietary Level f Aroclor 1260 (ppm) Control i 10 100 o TABLE XXIV 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: 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* HONS 068446 * Statistically significant difference at the 95 percent confidence level. \o o yttdiftil'tiai B l U I e 3 I ZQ4MVH 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_______ FemalesMalesFemalesMalesFemales 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 9 9 8 9 0 SNOW ** Statistically significant difference at the 99 percent confidence level. TABLE XXVI 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: Brain Dietary Level of Organ Weight Aroclor 1260 (g) (ppm)MalesFemales Control 1.96 1.95 1 2. 10 1.92 10 2.01 1.73 100 1.99 1.88 Final Body Weights Organ/Body Weight Ratio of Sacrificed Rats (g/100 g) (g) MalesFemalesMales_______ Females 0.320 0.560 613 348 0.412* 0.474* 509 405 0.349 0.504 575 . 343 0.382 0.650* 522 289 HONS 0 6 8 4 4 8 * Statistically significant difference at the 95 percent confidence level. JndUtttial B I O - T E S T Ja&Maio-Uei, }nc. 47 c. Histopathologic Findings Histopathologic examination of tissues and organs taken from ail animals from both the control and 100 ppm groups was conducted. Tables XXVII and XXVIII li3t 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.* *0NS 068449 JrtiHikial B I O - T E S I labaiatMi&i, 'Jnc. 48 o 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 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 = moderate 4. 0 = severe 5.0 = extreme r' o HONS 068450 u i -j - i - J i xawy'u2nyuci, J*c. 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 G rade 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 = seve re 5.0 = extreme HONS 068451 jtJUlhud B I O T E S T laioviiyuci, Stic. I oI 3. Twelve-Month Sacrifice a. Gross Pathologic Findings SO Gross pathologic findings among test animals were not I 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. o 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. ' i O WAS 06645^ ooo 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 Dietary Level (ppm)____________ Organ Weight (g) MalesFemales Organ/Body Weight Ratio (g/100 g) MalesFemales Organ/Brain Weight Ratio (g/g) MalesFemales Control i 10 100 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. HONS 0 6 8 4 5 3 HONS 0 6 8 4 5 4 Dietary Level teom) Control i 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 Weight Males (g) Females Organ: Kidneys Organ/Body Weight Ratio (g/100 g) Males Females Organ/Brain Weight Ratio (g/g) Males Females 4.04 3.84 3. 19 2.58** 0.692 0.625 0.738 0.724 1.97 2.06 1.58 1.39 4.00 2.78* 0.660 0.736 . 2. 16 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. /-vo ipnjfttnii/r i. Cft t 4 V. p Dietary Level (cpm) Control i 10 100 oo TABLE XXXI TEST MATERIAL: Arodor 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 (g) Males Females 0.778 0.756 0.796 0.460* 0.836 0.578 0.785 0.474* Organ/Body Weight Ratio (g/100 g) Males Females 0.133 0. 122 0.139 0.116 0.183 0.129* 0.150 0.127* Organ/Brain Weight Ratio (g/g) Males Females 0. 380 0.396 0.408 0.247* 0.457 0.308 0.365 0.284 * Statistically significant difference at the 95 percent confidence level. HONS 0 6 8 4 5 5 ,5 *8 9 0 /s i n ooo 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/100 g) (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. OS/t> ). \ | i o Dietary Level (opral Control i 10 100 oe TABLE XXXIII TEST MATERIAL: Arodor 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 F emales 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 i </> c Oo>' *Ul  'JniuAbual B l O * T E $ T 2c o oo Dietary Level (ppm) Cont rol i 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 (g) Males F emales 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 1.87 1.86 0.304 0.522 616 356 1.88 2. 15 1.90 1.67** 0.310 0.318 0.493 0.449 607 385 675 372 ** Statistically significant difference at the 99 percent confidence level. SNOW un O' o f>t +fst* 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. MGNS 060459 ?o TABLE XXXV TEST MATERIAL: Aroclor 1260 Two-Year Chronic Oral Toxicity Study - Albino Rat* Histopathologic Changes Twelve-Month Sacrifice Croup: Control Number of Animal* 5 Male* 5 Females Organ Examined Trachea Lung Urinary Bladder Trachea Lung Colon Findings Inc ids nee Trache itis Chronic respiratory disease Calculus 1 2 1 Tracheitis Chronic respiratory disease Paras ites 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 System 0.5 * minimal 1.0 a slight 2.0 a mild 3.0 a moderate 4.0 a severe 5.0 a extreme MONS 068460 3ndMbuaL B l O I 5 I labanaia-iM. Jnc. 3V TABLE XXXVI TEST MATERIAL: Aroclor 1260 Two-Year Chronic Oral Toxicity Study - Albino 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 Average 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 a extreme . MOMS 066461 . }ndullual B I O - T E 5 T Jaiotal&iiei, Jac. 60 o 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 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 MOMS 066462 . Dietary Level (ppm) Control i 10 100 o TABLE XXXVII TEST MATERIAL: Aroclor 1260 Two-Year CHronic Oral Toxicity- Study - Albino Rats Organ Weight and Ratio Data j Summary of Mean Values Final Sacrifice Organ: Liver Organ Weight Males (g) Females 22. 0 16. 3 Organ/Body Weight Ratio (g/ 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 95 percent confidence level. :: Statistically significant difference at the 99 percent confidence level. o T (/> O O' w o . Organ/Brain Weight Ratio (g/g) Males Females 10. 10 8.42 9.93 8.62 11. 20 9.26 13.40* 11.60* iw L ilb u a l B I O - T E 5 T 2a&o*ala\uu Dietary Level (ppm) Control i 10 100 o TABLE XXXDC 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 1. 15 0.96 1. 17 0. 72 1.09 0. 83 0. 89 0.75 Organ: Spleen Organ/Body Weight Ratio (g/100 g) Males Females 0. 182 0. 181 0. 178 0. 148 0. 131 0. 142 0. 138 0. 146 o : c '* \ r j. Organ/Brain Weight Ratio (g/g) Males Females 0. 520 0.492 0.529 0. 370 0. 509 0. 428 0.400 0.379 o l*o O' o Dietary Level (ppm) 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 Valuea Final Sacrifice Organ: Gonads Organ Weight Males (g) Females 2.52 0. 123 Organ/Body Weight Ratio (g/100 g) 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 Males (g/g) Females 1. 15 0.0628 1.61* 0.0718 1.56* 0. 0900 1.33 0.0584 s Statistically significant difference at the 95 percent confidence level. x' i CO O' O' Ul o Dietary Level (ppm) Control i 10 100 G TABLE XLI 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: Heart Organ Weight Males (g) Females 1. 87 1.54 1.98 1.45 1. 90 1.58 2.00 1.49 Organ/Body Weight Ratio (g/100 g) Males Females 0. 294 0.288 0. 304 0.294 0.225** 0.279 0. 313 0. 288 Q | t *j r _* ^ i | Organ/Brain Weight Ratio f Males (g/g) 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. o * Cn ttttotocooo i i o u iv L tlltu il B I O T E S T J a lw u jtM u ii, %ic. . Dietary Level (ppm) Control i 10 100 TABLE XLH TEST MATERIAL: Aroclor 1260 Two-Year Chronic Oral Toxicity Study - Albino Rato * Organ Weight and Ratio Data t Summary of Mean Values Final Sacrifice ' Organ: Brain Organ Weight (g) Males Females Organ/Body Weight Ratio (g/100g) 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. O' p a* 9 X SnJjiltuai B I O - T E S T Jalt&uzbyuci, 9*tc. 67 c. Histopathologic Findings Histopathologic examination of tissues and organs taken from all animals sacrificed after 24 months on test was conducted. Tables XL.III 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 (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 HONS 006468 Sndnlbual B I O - T E S T Jaiuy\aU'uei, 9*c. 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 HONS 069469 o TABLE XLHI TEST MATERIAL: Arodor 1Z60 Two-Year Chronic Oral Toxicity Study - Albino Rata Histopathologic Changes Final Sacrifice Group: Control Number of Average AnimalsOrgan ExaminedFindingsIncidenceGrade HONS 11 Males Heart Trachea Lung Liver Stoma ch 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 1.0 3 1.0 9 1.0 1' 1.0 2 1.0 1 1.0 3 1.0 8 1. 0 2 1.0 2 1. 0 1 1.0 1 1.0 1 1.0 1 1.0 1 1.0 2 1.0 oo TABLE XLIU continued TEST MATERIAL: Aroclor 1260 Two-Year Chronic Oral Toxicity Study - Albino Rats Histopathologic Changes Final Sacrifice Croup: Control Number of Animals Organ Examined Findings 14 Females X nar Co c O' o> 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 Incidence 7 9 13 3 2 1 2 3 5 1 4 3 6 i L 9 4 i o OB 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 -4 O oo TABLE XLIV TEST MATERIAL: Aroclor 1260 Two-Year Chronic Oral Toxicity Study - Albino Rats Histopathologic Changes Final Sacrifice Group: 1 ppm * Number of Average AnimalsOrgan ExaminedFindingsIncidenceGrade Heart Trachea Lung Liver Pancreas Stomach Spleen Lymph Node Kidney Testes Prostate Seminal Vesicle 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 Inflamma tion Inflammation 4 7 10 1. 1 1 2 .1 1 1 7 1 2 4 1 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 HONS 068472 Number of Animals 1 1 Males TABLE XLIV continued TEST MATERIAL: Arodor 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 X o ar lr> 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 , - 3 1 9 13 1 1 1 1 1 1 2 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 e TABLE XLIV continued TEST MATERIAL: Aroclor 1260 Two-Year Chronic Oral Toxicity Study - Albino Rata Histopathologic Changes Final Sacrifice Group: l ppm ' Number of Average AnimalsOrgan ExaminedFindingsIncidenceGrade 14 Females x o 2 Ui o O a> * * Stoma ch 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 1.0 1 1.0 11 1.0 1 1.0 1 1.0 3 2.0 1 1.0 4 1.0 9 1.0 3 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 61*890 Number of Animals 7 Males TABLE XLV TEST MATERIAL: Aroelor 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 Heart Trachea Lung Chronic focal myocarditis Thracheitits ' Chronic respiratory disease 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 . 1.0 1.0 1.0 o TABLE XLV continued TEST MATERIAL: Arodor 1260 Two-Year Chronic Oral Toxicity Study - Albino Rat# Histopathologic Changes Final Sacrifice Group: 10 ppm ' Number of Animals__________ Organ Examined Findings Incidence 14 Females Liver Pancreas Stomach Spleen Kidney X Uterus x Pituitary 4/1 Adrenal Gland o oo> . * _____________________ o- 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. 0.5 = minimal t. 0 = slight Grading System 2. 0 = mild 3.0 = moderate * ' 4.0 = severe 5.0 = extreme ' 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 ut "raniytavyo/- I S 3 1 - O I B TTMv1t" ?uC o oo TABLE XLVI TEST MATERIAL: Arodor 1260 Two-Year Chronic Oral Toxicity Study - Albino Rata Histopathologic Changes Final Sacrifice Group: 100 ppm Number of Average AnimalsOrgan ExaminedFindingsIncidenceGrade 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 1.0 1.0 2.0 1.0 2.0 1.0 2.0 1.0 1.0 1.0 2.0 1.0 1.0 1.0 1.0 1.0 MOWS 0 6 8 4 7 7 TABLE XLVI continued TEST MATERIAL: Aroclor 1260 Two-Year Chronic Oral Toxicity Study - Albino Rats Histopathologic Changes Final Sacrifice Group: 100 ppm- Number of Average AnimalsOrgan ExaminedFindingsIncidenceGrade Kidney (continued) Testes Prostate Thymus Adrenal Gland Calcified concretions in pelvis Aspermia Inflammation Cyst Telangiectasis Nodular hyperplasia i i i i. 3 l 1.0 1. 0 1.0 1.0 1.0 1. 0 Heart Trachea Lung Liver Chronic focal myocarditis Tracheitis Chronic respiratory disease Congestion Edema Vacuolar change (fatty) . 5 8 11 1 1 5 1.0 1. 0 1.0 1.0 1.0 1. 0 9o Number of Animals 15 Females X 2 O a * TABLE XLVI continued TEST MATERIAL: Aroclor 1260 Two-Tear 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 Hype rplasia 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 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 HONS 0 6 8 4 8 0 oo Group C T-I ' (X ppm) T-II (10 ppm) T-III (100 ppm) Sex M F M F M F M F TABLE XLVII TEST MATERIAL: Aroclor 1260 Two-Year Chronic Oral Toxicity Study - Albino Rate 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 e Average Grade 1.0 _ - _ - ynOMU/uaL o i w * i c a i jmc. G. Detailed Description of Tumor Findings Tumor 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. HONS 068481 oo Animal 'Cumber and Sex l-M 2-M ' 46-F 47-F 1 43-F 50-F 52-F 59-F , 64-F 66-F X o 2 to O' CD * CD Kl Location Abdomen Pancreas Abdomen Lymph node Abdomen Abdomen Abdomen Abdomen Adrenal gland Abdomen Abdomen TABLE XLVIII ` TEST MATERIAL: Arodor 1260 Two-Year Chronic Oral Toxicity Study - Albino Rata 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 o Animal Number and Sex 99-M 127-F 128-F 138-F 141 -F 151-F 152-F 5 x o * 05 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 Croup: 1 ppm Weight (grams) 25.00 60. 80 20.07 - - 14. 89 540.00 Size (cm) 6x3x1 5x6x2- - - - 13 x 15 x 2 Classification ^Chromophobe adenoma l Chromophobe adenoma ' Mammary fibroadenoma l Chromophobe adenoma ^ Mammary fibroadenoma is . < ,. - * Mammary fibroadenoma i Chromophobe adenoma ^Adenoma * Mammary fibroadenoma , Mammary fibroadenoma Months on Test 20 24 21 24 24 24 22 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 Mammary fibroadenoma Chromophobe adenoma i Mammary fibroadenoma , ^ Subcutaneous tumor `"Mammary fibroadenoma Chomophobe adenoma i- Fibroadenoma ir Mammary fibroadenoma Months on Test 24 24 24 23 24 24 Animal Number and Sex 22-F 233-F 234-F Location Left femoral region Pituitary Abdomen Pancreas o TABLE L continued TEST MATERIAL: Aroclor 1260 Two-Year Chronic Oral Toxicity Study - Albino Rats Description of Tumor Findings Group: 10 ppm Weight (grams) 56. 00 Size (cm) 6x8x2 Classification Subcutaneous tumor 60.82 6x4x3 Chromophobe adenoma ^ Mammary fibroadenoma t'Tslet cell adenoma Q Months on Test 6 24 24 o o *OD Ul  C5 2 TABLE LI TEST MATERIAL: Aroclor 1260 Two-Year-Chronic Oral Toxicity Study - Albino Rata Description of Tumor Findings Group: 100 ppm Animal Months Number Weight Size on and Se*Location(grams)(cm)ClassificationTest 244-M 264-M 281-F 293-F 294-F 30UF Pancreas Pancreas Abdomen Liver Abdominal cavity Liver 35.04 50.75 - 6x4x2 6x4x3 - ; Adenoma t^Islet cell adenoma (/Mammary fibroadenoma > Lymphosarcoma ^ Fibroma Lymphosarcoma 24 21 24 23 24 23 I Animal Kumbe r and Sex 302-F 308-F 311 -F 312-M 314-F Location Lymph node Pituitary Abdomen Pituitary Abdomen Q TABLE LI continued TEST MATERIAL: Aroclor 1260 Two-Year Chronic Oral Toxicity Study - Albino Rate Description of Tumor Findings Group: 100 ppm Weight (grams) 14. 00 26. 00 Size (cm) - 4x3x2 1x2x1 5x4x3 Classification y Lymphosarcoma Chromophobe adenoma Mammary fibroadenoma , (Mammary fibroadenoma ^Chromophobe adenoma Mammary fibroadenoma x n x (A 3 Months on Test 24 24 24 24 24