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R EPO R T TO MONSANTO COMPANY TW O-Y EA A CHRONIC ORAL TOXICITY WITH AROCLCR 1260 IN ALBINO RATS NOVEMBER 12, 1971 IBT NO. B7298 L Introduction At the r e q u e s t of Monsanto Company, a tw o -y e a r chronic ora l toxicity study was conducted using albino rats to determine the potential to xicity of A r o c l o r 1260, Lot No. AK-3. The following re p o rt p r e s e n t s the results of this investigation. > 000082 11100884 Food con su m p tio n and body weight gains w e r e not altered at ar.y le v e l of A r o c l o r 1260 fed. The n u m b e r of a n i m a l s dying and the time which the deaths occurred did not vary among the test and control grou Hematological and clinical blood chem istry studies conducted after 3, 6, 9, 12, 13, or 24 m onth s did not r e v e a l a ny affe cts r e l a t e d to Aro 1260. Urine analyses failed to reveal any differences between test and control animals. At s a c r i f i c e a f t e r 3, 6, or 12 month s on t e s t o r g a n w ei ghts, o rg a n body weight and organ to brain weight ratios disclosed several randoml] occurring intergroup differences. The lack of any consistent dose relat r e s p o n s e and the absence of any d e le te rio u s histo path olo gic change conf: that these d if f e r e n c e s w e re not re la te d to the inge stion of A ro c lo r 1260. At the final s ac rifice after 24 months on test, the liver weights and l i v e r to body w eight or b r a i n weight ra tios w e r e significantly elevated in the r a f t f r o m the T-UI g roup. Histologic e x a m i n a tio n of the liv e rs f r o m the T - U I gro up r e v e a l e d s e v e r a l a n i m a l j with v a c u o la r change. T! le sio n is m orp h o lo g ica lly indicative of fatty degeneration. Specific fat tains c o n f i n e d the p re sen c e of fat in these vacuoles. Focal hypertroph and focal h y p e rp la s ia were also found in the l iv e r s from animals fed Aro 1260. A0H OC37 263 ( H yperplasia of he urinary bladder was found in in animal from : h ^ * control group but not in any of the te st animals. The incidences and types of all tum ors w ere about the same in all r groups, including the control group, and are considered normal for rats of this age. V. Respectfully submitted, INDUSTRIAL BIO-TEST LABORATORIES, INC. R eport prep ared by: P h ilip Sm ith, B. S. Assi stant Toxicologist Rat Toxicity Report approved J P a u l L. W right, P h . D, Section Head, Toxicology L. Kepli^gprf, ?h . M anager, Toxicology N ovem ber 12, 1971 lam tsjn ACM U 000084 FW0R8B rv .I in . -P----r--o----c---e---d---u---r---e---- . A. Experim ental Animals - - 3~1 The Animals employed in the test w ere C harles River s tra in ' \ albino r a t s . F o u r h u ndred ra ts (200 m ales and 200 fem ales) w ere selected for the experim ent, ear-punched with the animal num ber assigned and housed individually in standard,w ire-bottom ed, steel rat cages. Each cage bore a color-coded card identifying the rat with r e spect to p ro je c t n um ber, dose level assignm ent, individual anim al number and sex. B. Organization of Groups A s tru c tu ra l outline of the experim ent is given in Table L Grouo TABLE I TEST MATERIAL: A rc elo r 1260 Tw o-Y ear Chronic Oral Toxicity Study - Albino Rats Outline of Experim ent N um ber of Animals Male Female Dietary Level (oom) Control 50 50 None Administered T r : 50 50 1 T-II 50 50 10 T - III 50 50 100 Charles River Breeding Laboratories, North Wilmington, M ass. ( ACH OC3722 F0008R7265 0 0 0 0 8 .") C. Dicta, Feeding and Toad Consumption All d ie tj w ere p rep ared in the central d iet room of this ' 's t* r lab o rato ry . The basic ration from which all d ietj were constructed' wa a standard, pulverized stock rat ration*. The diet for any given te s t group wa* p rep ared by blending the calculated amount of A rocior 1260 with a pre-w eighed portion of the stock ration in a H obart m ix er. . F resh diets w ere prepared each week and every rat was offered an am ount of food sufficient for ad libitum feeding. Food consumption was recorded for five ra ts of each sex in ever group weekly for the fir s t th ree months.and monthly for the next nine m onths. Thereafter, periodic spot cheeks w ere made. i D. Bodv W eights and W eight Cains In itially , the, body w eight of each r a t in e v e ry group w as d e t e r m ined and recorded. T hereafter, individual weighings were made weekly f o r the f i r s t 13 w eek s and m o n thly th e r e a f te r u n til the con c lu s ion of the i n v e s tig a tio n .___________________ ___ _______________________ - ________ ; E. M ortality and Reactions * " - Checks for m ortality and abnormal behavioral reactions were .m ade daily throughout the investigation. 7 -7 ' F . Hematologic Studies and Urine Analyses Blood studies, including determ inations of hemoglobin c o n c e n tra tions, hem otocrit value, erythrocyte count and both total and differential P u rin a Rat Chow, Ralston Purina C o ., St. Louis, Mo. AC* C03 266 00008G FonORRS Cl le u k o c y te c o u n ts . w a r e co n d u cted upon five m a le * and five fem ales f - o m ' I b o th th e c o n t r o l and 100 p p m g ro u p s . * U rine analyses for the presence of glucose, albumin, m i c r o - a co p ic e le m e n ts , and d e te rm in a tio n s of pH and specific gravity w ere c o n ducted upon urine sam ples at the same time intervals and from the sam e ' 'i anim als as those employed for the blood studies. \ T h e s e s tu d ie s w e r e conducted a f te r 3, 6, 9. 12. 18, and 24 month; of feeding* G. C linical Blood C hem istry Studies D e te r m in a t io n s of blood u r e a n itro g e n C o n cen tratio n (BUN)* s e ru m alkaline phosphatase activity (SAP], fasted blood glucose .concen tra tio n and seru m glutam ic-pyruvic tran sam in ase activity (SGPT) w ere c o n d u c te d a f t e r 3, 6, 9, 12, 28, and 24 m o n th s of feeding upon the s a m e ra ts as w ere the routine blood studies. H. Pathologic Studies When an anim al succumbed during the test period, a gross autopsy w as p e rfo rm ed . In those cases when p o stm o rtem autolysis was not a d vanced, re p re se n ta tiv e tissu es w ere taken and p re se rv e d in ten p ercen t form alin solution for possible future histopathologic study. A f t e r 3, 6, and 12 m o n th s of te s tin g , five a n im a ls of each s e x fro m each group w ere sacrificed and subjected to complete gross patholoj'c exam inations. AOH 0C 37Z 000087 i F000889 , A bsolute organ w eights w ere re c o rd e d and organ to body weight, I and organ to b ra in weight ratio* computed. The following organ* w ere included; liver, kidney*, .spleen, gonads, h eart and brain. These data w,ere then lu b je c te d to s ta tis tic a l .analysis. An A nalysis of V ariance was conducted first and significant effects disclosed by that treatment were fu rth er studied by " f '- te s ts . Complete m icroscopic examination* w ere conducted upon the tis s u e * and o r g a n s f r o m a ll c o n tro l and 100 p p m g ro u p rat* s a c r i f i c e d . a f t e r 3, 6, o r 12 month* of te s t in g . The following tis su e * and o rg a n s we; included in the examinations: h eart, trachea, lungs, liver, pancreas, esophagus, stom ach, sm all intestine (duodenum, jejunum and ileum), caecum , colon, spleen, lymph nodes, kidneys, urinary bladder, gonads, prostate gland, seminal vesieles, 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 aforem entioned tissues were p re p a red and stained with H em atoxylin-iosin stain, *" A fter two years of feeding, all surviving anim als were sacrificed aad subjected to complete g ross pathologic examination. The absolute weights of the liver, kidneys, spleen, gonads, h eart and brain were recorded immediately after sacrifice. ADM 0 0 3 7. 268 000083 M icroscopic exam inations were conducted upon tissues and organs from selected anim als dying during the experim ent and upon all anim als from the final sacrifice. T issu es and organs exam ined w ere the same as those previous m entioned. J. T u m o r Incidence ar.d C la ssificatio n A tabulation of the incidence of tum or form ation in each group w a s m a d e a t the conclusion of the investigation. In addition, tu m o r datj fo r individual anim als including location, weight, si2e and pathologic classification w ere recorded. AC* CC3727 000089 JOOO&91 rV. R e s u l t a A- Bodv Weights and Weight Cains I1 i \ Tha m ala and fem ale body weight data a re assem bled in Table I I ;/' The s data in this table also include the 3, 1a2 and 24 m o n th to ta l w eight gains. T h e re w ere no significant effects due to ingestion of the compound ACP COI 270 F000892 GODO':)) dietary Level of A ro clo r 1260 (ppna) Sex Control M F to 1 i-* M F 10 ~'A~4 2 100 s M F M F oo TA BLE II T E ST M ATERIA L; A ro c lo r 1260 Tw o-Y ear Chronic O ral Toxicity Study - Albino Rata Body Weight and Total Weight Gain Data Sum m ary of Mean Valuea Body Weight 90-Day (grama) Total Weight Week: Ga in 0 1 2 3 4 5 6 7 8 9 10 11 12 13 ( R r a m a / r a l l 133 203 245 313 362 373 391 409 424 440 440 449 467 474 136 178 190 219 244 254 259 265 270 276 281 278 290 288 341 152 133 192 250 322 361 374 394 416 428 448 450 474 479 490 136 167 IU9 218 241 252 256 2 6 | 268 273 277 281 290 288 357 152 133 204 245 317 368 382 400 417 436 448 461 467 475 481 136 174 190 217 242 254 260 263 268 274 281 279 285 288 348 152 133 208 247 319 363 375 394 425 437 451 460 479 486 500 136 173 IU8 222 240 253 258 262 265 267 270 275 275 280 367 144 Ov oo o :x o CO oo #* * ii * .. i Dietary Level of A ro c lo r 1260 (ppm) Sex Zontrol M F 1M F 10 M F 100 M F OO T A B LE II continued T E S T M ATERIAL: A r o c l o r 1260 Two-Year Chronic Oral Toxicity Study - Albino Rale Body Weight and Total Weight Gain Data Summ ary of Mean Values Body Weight 12-Month (grams) Total Weight Month; Gal 45 6 7 8 9 10 1 1 12 ( g r a m s 498 513 565 593 622 642 667 688 70 1 568 297 310 322 333 345 359 374 383 390 254 516 547 578 600 628 643 66 8 688 699 566 298 307 314 321 333 340 353 367 * 379 24 3 496 526 551 581 60 6 633 660 685 709 576 291 306 314 311 340 358 370 381 388 252 522 555 5 80 607 611 650 681 707 717 584 289 302 307 314 326 333 342 347 361 227 000092 KnnnR94 o* * c* o '1 < Vj oo Dietary Level of A ro c lo r 1260 (ppm) Sex Control M F 1M F 10 M F 100 M F O o >n t-oJ x wo o TACKLE II continued 0 T E ST M ATERIA L: A ro c lo r 1260 Tw o-Y ear Chronic O ral Toxicity Study - Albino R ats Body Weight and Total Weight Gain Data Sum m ary of Mean Valuea Body Weight 24-Month (grama) Total Wcigl Month: Gain IS 14 IS 16 17 18 19 20 21 22 23 24 fg r a m a / ra i 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 5 30 484 525 509 415 521 385 728 745 776 761 76 B 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 64 1 380 386 417 414 435 453 471 481 500 507 485 537 512 448 508 401 StiHUUI/if *J B. Food Consumption r \ The data obtained fro m the food consumption m easurem ents c o n d u c te d d u r in g th e f i r s t 12 m o n th s of feeding a r e s u m m a riz e d in T a b le II T hese data revealed no significant difference between test and control ra ts. The periodic checks conducted during the rem ainder of the investigation also revealed no outstanding differences between test and control animals. O A O CC 3 7 0 0 274 TABLE III ia TEST MATERIAL,: A ro clo r 1260 Tw o-Y ear Chronic O ral Toxicity Study - Albino Rate Food Consumption Data l. ( t 1 ietary Level of A ro c lo r 1260 (ppm) . Sex Control M F Summ ary of Mean Valueii t \ Food Consumption (gram a/rat/sevcn days) Average Food j Week: Consumption ' 1 2 3 4 5 6 7 8 9 10 II 12 13 ( ( f r a.m..e./ r.a.t /seven:--d-ava.a'r 94 160 175 163 137 137 225 197 204 IBB 191 194 196 71 140 144 107 104 133 208 154 165 151 146 150 151 174 140 1 0$ 10 53 1 100 O O KJ > t-nj o'x M i i a 154 151 169 201 116 200 198 201 193 169 187 194 F 95 u a 97 139 160 107 162 139 165 149 150 143 147 M 106 146 144 142 190 136 196 214 214 192 191 199 200 F 94 124 128 124 179 90 190 167 155 151 150 149 152 M F 121 150 156 117 187 124 121 190 196 186 184 199 189 89 93 123 151 151 101 193 136 140 144 144 147 146 175 136 175 143 163 135 o ou> r- letary Level of A ro c lo r 1260 (ppm) Sex 4 Control M 196 F Hfl 1 M * 196 F I4B 10 M 186 F 142 100 M 179 F 156 TABLE HI continued TEST MATERIAL: A ro clo r 1260 Tw o-Y ear Chronic O ral Toxicity Study - Albino Rata Food Consumption Data Sum m ary of Mean Valuoe Food Consumption (gram s/rat/seven days) Month; 5 6 7 8 9 10 IB9 168 147 163 184 179 154 136 121 138 152 160 200 189 192 179 181 182 163 141 163 160 153 157 191 . 188 193 197 197 168 138 145 144 144 151 136 170 180 188 186 ` 166 181 127 147 144 134 132 162 Average Food C onsum ption 11 12 ( g r a m a / r a t / s e v e n d a y s ) 170 187 141 127 176 142 172 164 143 ' 132 186 151 164 196 139 141 186 142 188 180 149 139 * 180 143 vo % oo ..I vV. u F n o o W 00 276 1 C. M o rta lity and R eactions A frequency distribution of n atu ral deaths occurring during the in v e stig a tio n a p p e a rs in T able IV. No untow ard behavioral reactio n s w ere noted among any of the anim als em ployed in the investigation. ynnw *3 A0* GC37 00 277 ) Dietary Level (ppm) Sex Control M F 1M F. 10 M F 100 M F T A B L E IV T E S T M A TER IA L: A ro c lo r 1260 Tw o-Y ear Chronic O ral Toxicity Study - Albino Rata M ortality Data Frequency D istribution of Doathe Frequency Distribution of Deaths M onths; 1-3 4-6 7-9 10-12 13-15 16-18 19-21 000 2 17 6 000 1 3 5 7 00 1 1 4 7 5 000 2 3 3 6 1 10 2 4 7 8 000 3 2 4 5 10 0 2 2 8 6 0 22 0 3 5 7 22-24 9 3 8 5. 6 3 9 4 Total Dead Number Tested 25/35 19/35 26/35 19/35 29/35 ' 17/35 29/35 23/35 O Does not include the five anim als of each sex from every group sacrificed for interim pathologic studies. LE0 0 "u* 19 D. H e m a to l o g ic and Clinical Blood C h e m i s t r y Studies^ M ean m ale and fem ale hem atologic and clinical blood c h em istry d a t a a r e s u m m a r i s e d l a T a b le s V th ro u g h DC. Values for all p aram eters Investigated w ere within the norm al ran g e fo r the albino ra t. No significant d ifferences between test and contrc Talues were observed. FoniW l ACM CC3T3 0 0 279 I J J i s a i u ts Dietary Level (ppm) Control Sex 3 M 14.0 F 9. 1 TABLE V TEST MATERIAL: A rocior 1260 Tw o-Y ear Chronic O ral Toxicity Study - Albino Rata Hem atologic Data Sum m ary of Mean Value* Total Leukocyte Count (thousand*/m m ^) Month: 6 9 12 18 24 3 15.4 10. 1 11. 1 9 .9 11.2 8. 1 9.4 4.7 7.6 8.8 7.6 7.5 Erythrocyte Count (mill ion a/min'*) Month: 6 9 12 18 8.2 8.7 8.8 7.6 7.7 7. 3 7.8 7.7 24 6.5 6.8 M 10.8 11.1 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 vo it o oIP "I 1 I vi> OC 280 Dietary Level (ppm) Sex 1 M 17* 1 Control F 16.9 O TABLE VI TE ST M ATERIAL: A ro clo r 1260 Tw o-Y ear Chronic O ral Toxicity Study - Albino Rata Hmatologie Data Sum m ary of Mean Values Hemoglobin Concentration (g/100 ml) Month: 6 9 12 18 24 H em atocrit Valuo <%> 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 I6l 1 17.2' 14.0 15.3 15.9 14.5 100 F 16 .1 17.0 13.7 15.6 15.3 12.9 49 47 43 43 41 38 48 47 41 44 39 32 281 O ** <=> 5 nou Uyfii SoJ *, ( Dietary Level (ppm) Sex 3 Control M 82.0 r 83.0 TABLE VII T E S T M ATERIAL: A ro c lo r 1260 Tw o-Y ear Chronic Oral Toxicity Study - Albino Rate Hematologic Data Summary of Mean Valuee 6 86.6 B6.6 Differential Leukocyte Count (Number of Celle per Hundred) Lymphocyte a Neutrophile Month: Month; 9 12 18 24 3 6 9 12 18 80.4 78.8 79.0 65.4 16.0 11.4 18.6 20.6 20.0 86.8 89.0 70.2 61.4 15.4 11.6 11.8 10.0 29.2 24 32.2 36.0 M 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 7.6 13.8 10.0 15.8 19.4 22.6 17.0 24.6 17.4 31.6 34.2 C5 o o ZBZ 0 0 ' "A ! i IN O oa OC 283 GOO Dietary Level (ppm) Sex 3 Control M 0.6 F 0.6 M 0.0 100 F 0.0 TABLE VII continued TEST MATERIAL; A roclor I60 Tw o-Y ear Chronic Oral Toxicity Study - Albino Rata Hematologic Data Sum m ary of Mean Valuea Differential Leukocyte Count (Number of Celia per Hundred) Monocyte a Eosinopliila Monili; Month; 6 9 12 i a 24 3 6 9 12 0 .0 0 .0 0.4 0. 2 1.2 1.4 2.0 0 .0 0.0 0.0 0.2 1.0 1.0 1.8 1.4 0.2 18 0.8 0.6 24 1.6 1.6 0.0 0.0 0.0 0.4 0.8 0.0 0.0 0.0 0.4 0.2 1.4 0 .8 0 .8 1.0 1.2 1.0 0.4 0.4 0 .8 0.8 1.6 0 .0 a CD *> oX o o til N 1> O Dietary Level (ppm) Control 100 o I t a b l e ! VII continued TEST M ATERIAL; A ro c lo r 1260 Tw o-Y ear Chronic O ral Toxicity Study - Albino Rata Hem atologic Data Sum m ary of Mean Values Differential Leukocyte Count (Number of Celia p er Hundred) Baaophila Month: Sex 3 6 9 12 18 M 0.0 0.0 0.0 0.0 0.0 F 0.0 0.0 0.0 0.0 0.0 M 0.2 0.0 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 0.0 28 4 O to X o Uoi t1 Dietary Level (ppm) Sex 3 Control M 38 F 33 M 33 100 F 29 OO TABLE VIII TEST M ATERIAL; A ro c lo r 1260 T w o-Y ear Chronic O ral Toxicity Study - Albino Rata Clinical Blood C hem istry Data Sum m ary of Mean Value Srum Glutamic-Pyruvic (Dade Units) Month; 6 9 12 18 48 45 45 42 39 38 42 32 24 36 30 36 Blood Urea Nitrogen Concentration (mgs %| Mouth; 9 12 18 24 17 IS 12 10 14 15 14 16 15 9 13 II 39 42 43 31 36 37 50 40 32 33 14 15 17 16 16 15 * 15 15 14 13 12 14 1 L Dietary Level (ppm) Sex 3 M 128 Control F 130 f 100 M 118 F 117 TA B LE IX TEST MATERIAL) A ro clo r 1260 Tw o-Y ear Chronic O ral Toxicity Study - Albino Rate Clinical Blood Cliemielry Data Summary of Mean Valuee Fasted Blood Glucose C o n cen tratio n (mg s%) Month: 6 0 12 18 123 89 88 138 118 115 92 134 24 99 109 Serum Alkaline Phosphatase Activity (King-Armslrong Units) Month: 3 6 9 12 18 28.6 24.7 21.5 20. 3 16.2 18.9 17.8 10.6 11.9 16.8 24 22. 3 20. 2 118 116 135 146 98 116 115 138 146 94 37.8 12.0 21.8 21.9 12. 1 7 .6 23.9 11.7 11.9 7.8 16. 1 12.4 UNi ACM 00374 S U rine A nalyses M a u i m a la and fem ale u rin e a n aly se s data a re sum m arised in T a b le s X th ro u g h XXI. Da te rm in a tio n s for glucose c o n cen tratio n w ere negative for all * ra ts a t every in te rv a l of exam ination. -v No differences w ere noted between the urine from control and test anim als at the intervals of examination. jnoosflS ACM 00 287 !  TABLE X T E S T M ATERIAL: A ro c lo r 1260 Tw o-Y ear Chronic O ral Toxicity Study - Albino Rata Urine Analyses Data Sum m ary of Mean Values Dietary Level (ppm) Sex 3 - Mn Control Fn S i* Glucose Month: 6 9 12 nnn nnn IO CD 00 O Oo O1 ^0 -2 M n it n n 100 Fn n n n Key: n - negative t = tr a c e ; le s s than 30 m g / 100 m l u r in e i I s 30 lo 100 m g / 100 m l u rin e -t 2 s 100 to 300 m g / 100 m l u r in e *3 s 300 to 500 m g / 100 m l urine 4 =m o re than 500 mg / 1 00 m l u rin e 18 24 nn nn nn nn Albumin Month: 3 6 9 12 18 24 n n ft ft 42 43 n n n n ft 42 n l ft ft 4 1 43 n n n n 4 1 44 } i O Dietary Level fppm ) Sex a Control *3* 100 MN FN MN FN u TA B LE XI TEST MATERIAL: A ro c lo r 1260 Tw o-Y ear Chronic O ral Toxicity Study - Albino Rata Urine Analyses Data Sum m ary of Mean Values M icroscopic Elements Month: 6 9 12 18 NNNN NNNt 24 41 t pH Month: 3 6 9 12 18 24 776 776 8a 7 86 6 N N N N1 N N N tt 77676 6 7 8 6 7 6 6 0 C m i/i Key: Normal 1 s trace; less than 5 per low power field r~> 4 1 = 5 to 10 p e r low p o w e r field O 4 2 s 10 to IS p e r low p o w e r fie ld ' ' 43 s m o re than IS p e r low pow er field CroO io N0 O' Dietary Level (ppm) Control 100 T Afa L E XII T E S T M A T E R U L : A ro clo r 1260 T w o-Y ear C hronic O ral Toxicity Study - A lbino Rata Urine Analyaca Data S u m m a r y o f M ean VaKuee Sex 1 M 1.029 F 1.020 M 1.021 F . 1.016 6 1.022 1.019 1.025 1.023 Specific G ravity Month: 9 12 1.033 1.027 1.025 1.024 1.031 1.035 * 1.030 1.029 18 1.042 1.032 1.043 1.028 24 I.0 S I 1.039 . 1.039 1.045 vO T O 290 1+J+UuaJ. 3 1O * T E S T 30 T Pathologic Studies 1 T h re e -M o n th S a c rific e a* C ro s s Pathologic Findings No outstanding differences w ere noted between test and control rats upon gross pathological examination. b. Organ Weight and Organ to 3odv and Organ to B rain Weignt Ratio Data The results of the statistical analyses conducted on a b s o lu te o rg a n w eig h ts, o rg an to body1w eight and o rg an to b r a i n w eig h t ra tio s a re su m m arized in Tables XIII through XVIII. Significant differences between a test group and the con tro l group a re designated by a ste ris k s following the test v alues. Organ weights, organ to body weight and organ to b rain weight ratios disclosed several randomly occurring intergroup difference The lack of any consistent dose related resp o n se and the absence of any deleterious, histopathologic change confirm that these differences w ere not re la te d to the ingestion of A roelor 1260. AOM C03 7* 291 0 "\ oo a Dietary Level of A ro clo r 1260 (ppm) C o n tro l ! 10 100 ;i * T A B L E XIII T E ST MATERIALS A ro c lo r 1260 T w o-Y eir Chronic O ral Toxicity Study - Albino Rata Organ Weight and Ratio Data Three-Month Sacrifice Sum m ary of Mean Valuea Organ: Liver > O rgan Weight fg) Malea F em alea 21.4 13.0 20.4 13.2 24.0** 12.2 29.5** 14.5 Orgmn/Body Weight Ratio (g/100 g) M alea Fem alea 4.13 4.16 3.90 4.59 4.48 3.61 5.73a* 4.58 O rgan/B rain Weight Ratio (g/g) M alea Fem alea 10.3 6.82 9.98 6.86 11.8 6.38 14.4** 7.72 3 Statistically significant difference at the 99 percent confidence level D :> o \ h. o ) oUl n<Jt ui J oI *000915 O Dietary Level of A ro c lo r 1260 (ppm) C o n tro l l 10 too o TA B LE XIV TE ST MATERIAL: A roclor 1260 T w o-Y ear C hronic O ral Toxicity Study - Albino R ata Organ Weight and Ratio Data Three-Month Sacrifice Sum m ary of Mean Values Organ: Kidneys O rgan Weight <g> M ales Fem ales 4.03 2.49 4.37 2.62 4.00 2.61 4.00 2.52 Organ/Body Weight Ratio ( g /l 00 g) M ales Fem ales 0.762 0.802 0.838 0.911 0.747 0.779 0.782 0.793 O rgan/B raln Weight Ratio (g/g* M ales Fem ales 1.95 1.31 2.14 1.36 1.96 1.37 1.96 1.35 ' >o K) 1 U> to Oou* Dietary Level of A ro clo r 1260 (ppm) Cont rol 1 10 0 100 G Q Kj Oto Uooi "si o 4 T A B L E XV TE ST M ATERIAL: A ro c lo r 1260 Ttoo-Y car Chronic O ral Toxicity Study - Albino Rata Organ Weight and Ratio Data Three-Month Sacrifice Sum m ary of Mean Values Organ: Spleen o O rgan Weight lg) Male* Fem ales 0.766 . 0.578 0.846 0.516 0.878 0.672 0.718 0.556 O rgan/Body Weight Ratio (g/100 g) M ales Fem ales 0.150 0.184 0.161 0.180 0.156 0.187 0.140 0.177 O rg an /B rain Weight Ratio (g/g) . Males Fem ales 0.371 0.302 0.412 0.269 0.411 0.331 0.352 0.297 1 1 I 4 i % Dietary Level of A roclor 1260 (ppm| Control 1 10 100 TADLE XVI TEST MATERIAL! A ro c lo r 1260 TWo*Year Chronic O ral Toxicity Study Albino Rata O rgan Weight and Ratio Data Three-Month Sacrifice Sum m ary of Mean Valuea Organ; Gonads O rgan Weight (g) M ales Fem ales 3.60 0.114 3.67 0.128 3.83 0.121 3.71 0.138 Organ/Dody Weight Ratio (g/100 g) M ates Fem ales 0.698 0.0370 0.704 0.0450 0.715 0.0368 0.725 0.0429 O rgan/B raln Weight Ratio (g/g) M ales Fem ales 1.74 1.60 0.0599 0.0666 1.89 0.0636 1.81 0.072a % Dietary Level of A ro c lo r 1260 (ppm) Control 1 10 100 r SJ TABLE XVII * TEST MATERIALS A ro c lo r 1260 Tw o-Y ear Chronic O ral Toxicity Study - Albino Rata Organ Weight and Ratio Data Three-Month Sacrifice Sum m ary of Mean Valuca Organs H eart O rgan Weight (g) M alea Fem ales 1.59 1.05 1.57 1.01 1.58 1.04 1.52 0.946 Organ/Body Weight Ratio (g /1 0 0 g) M alee Fem ales 0.307 0.339 0.300 0.353 0.296 0.311 0.298 0.297 O rgan/B raln Weight Ratio (g/g) M ales Fem ales 0.767 0.551 0.765 0.526 0.781 0.546 0.743 0.505 tk, n I C r j FflftfYH-8 AOM 00375 II ui \ Dietary Level of A ro clo r 1260 (ppm) Coni rot a 1 10 100 O TABLE XVIII TEST MATERIAL: A ro clo r 1260 T w o-Y ear C hronic O ral Toxicity Study - Albino R ats Organ Weight and Ratio Data Three-Month Sacrifice Sum m ary of Mean Values Organ; Drain O rgan Weight (g) Malea Fem ales 2.07 1,91 2 . OS 1,92 2.0 1.91 2 . OS 1.89 Organ/Body Weight Ratio (g/100 g) M ales F em ales 0.402 0.616 0.392 0.672 0.380 0.572 0.400 0.593 Final Body Weights of Sac rificed Rata (y> M ales Fem ales 518 314 523 287 536 337 517 321 i t o> f iUn. r O' ACM 0C3755 7 c. Histooatholooic Findings H istopathologic exam ination of tissu es and organs ta k e n f r o m a ll a n im a ls fro m b o th the co n tro l and 100 ppm groups was conducted. T a b le s XDC a n d XX l is t a ll h is to p a th o lo g ic changes noted. All of the lesions noted in the m icroscopic exam ina tion of tissues were those of spontaneous disease and are not unusual for the albino rat. The m ost frequent findings w ere lesions in the trachea and lungs, indicating chronic murine pneumonia. These oc c u rre d in the control as well as the rats fed A r o d o r 1260. K p ,n rw 2 0 AO*' C037 0 0 293 OI I C3 I 33 TAB LZ XIX TEST MATERIAL: A roclor 60 T w o-Y ear Chronic O ral Toxicity Study - Albino Rats Histopathologic Changes Three-Month Sacrifice Croup: Control N u*m b e r of Animals Organ Examined Findings 5 Males Trachea Lung U rinary bladder Tracheitis Chronic resp irato ry disease Hyperplasia 5 Fem ales Lung Chronic resp irato ry disease Averag Incidence Grade 1 1.0 1 1.0 3 1.0 1 1.0 All other tisiu e i and organs were normal histologically. Grading System 0 . 5 minimal 1 . 0 slight 2 .0 * mild 3 . 0 moderate 4.0 * severe 5.0 * extrem e *000921 A0M 003757 299 oc B I - r t * r 0. 9 TAB LE XX T E S T M ATERIAL; A ro c lo r 1260 T w o-Y ear Chronic O ral Toxicity Study * Albino Rats Histopathologic Changes Three-Month Sacrifice G ro u p : 100 p pm H um ber of Animals Organ Examined Findings 5 Males Trachea Lung Tracheitis Chronic respiratory disease 5 Fem ales Trachea Lung Kidney Tracheitis Chronic respiratory disease Focal lymphoid infiltration " A veragi Incidence G rade 4 1.0 2 1.0 3 1.0 2 - 1 1.0 1.0 All other tissues and organs were norm al histologically. Grading Svstam 0.5 = m inim al 1 0 x s l i g h t 2 .0 m ild 2 0 * m o d erate 4.0 severe 5 . 0 extrem e 1000922 A0H 00375. 00 300 0 ( V' I c 3 I 40 2* Six-M onth S a c r if ic e a G r o s s P a th o lo g ic Finding No outstanding differences were noted between test and control animals w b O r g a n Weight and Organ to Body and O r g a n to- B r a i n Weight Ratio Data The r e s u lts of the s ta tistic a l a n aly se s conducted on a b so lu te organ weights organ to body weight and organ to brain weight r a t i o s a r e s u m m a r i z e d in T a b le s XXI through XXVI* O rgan weights, organ to body weight and organ to b ra in weight ratios disclosed several randomly occurring intergroup differences. The lad e of any consistent dose related response and the absence of any deleterious histopathologic change confirm that these differences w ere n o t re la te d to the ingestion of A ro elo r 1260. F .0 0 0 9 2 3 ACH 0C375 OC 301 O Dietary Level of A ro clo r 1260 (ppm) Control 1 10 100 o TABLE XX! TE ST M ATERIAL: A ro c lo r 1260 Tw o-Y ear Chronic O ral Toxicity Study - Albino Rata Organ Weight and Ratio Data Six-Month Sacrifice Sum m ary of Mean Valuea Organ: Liver o O rgan Weight <g) M ales Fem ales 22.9 13.1 14.8** 15.1 19.0* 10. 5** 24.4 11.6 Organ/Body Weight Ratio (fi/100 g) M ales Fem ales 3.74 3.77 2.92** 3.74 3.31* 3.08* 4.69* 4.03 O rgan/B ratn Weight Ratio <g/g> M ales Fem ales 11-7 6.71 7.05** 7.86 9.45 * 6.07 12.3 6.17 y |* U U * S ta tis tic a lly significant d iffe re n c e a t the 95 p e r c e n t confidence le v e l. *< S ta tis tic a lly s ig n ific a n t d if f e r e n c e a t the 99 p e r c e n t co n fid en ce lo v el. 39ro r \ J % B l' TEST AC 0C37 TABLE XXII TE ST M ATERIAL: A r o d o r 1260 Tw o-Y ear Chronic O ral Toxicity Study - Albino R ats Organ Weight and Ratio Data Six-Month Sacrifice Sum m ary of Mean Values Organ; Kidneys Dietary Level of -A ro d o r 1260 (ppm) O rgan Weight (gl M ales F em ales Organ/Body Weight Ratio <g/100 g) M ales Fem ales O rgan/B raln Weight Ratio (g/fi) M ales Fem ales Cont rol 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 O 100 3.85 3.92 2.35 2.35 0.670 0.753 0.6B4* 0.814 uo u> * Statistically significant difference at the 95 percent confidence level. 1.92 1.97 1.36 1.25 N ''~N,y O % T A LE XXIII TE ST M ATERIAL: A ro c lo r 1260 Tw o-Y ear Chronic O ral Toxicity Study - Albino R ats . Organ Weight and Ratio Data Six-Month Sacrifice Sum m ary of Mean Valuea Organi Spleen Dietary Level of A ro c lo r 1260 (pl>m) Control 1 10 100 Organ Weight (gl Males Females 0.7S2 0.684 0.754 0.908 0.836 0.566 0.636 0.443* O rgan/Body Weight Ratio (g /1 0 0 g) Males Females 0 . 122 0.196 0.148 0.220 0. I46> 0.167 0.122 0.151 O rgan/B raln Weight Ratio fg/gl Males F em ales 0.384 0.350 0.359 0.472 0.416 0.320 0.327 0.236* * S tatistic ally significant d ifferen ce at the 95 p e r c e n t confidence level. AO 0037 OO t a b l e XXIV TEST M ATERIAL: A ro c lo r 1260 T w o-Y ear Chronic O ral Toxicity Study - Albino Rata Organ Weight and Ratio Data Six-Month Sacrifice Sum m ary of Mean Valuea Organ: Gonads Dietary Level of A ro c lo r 1260 (ppm) Cont rol 1 10 100 O rgan Weight (gl M alea Fem ales 3.55 0.0960 3.21 0 . 120a 3.56 3.53 0.0968 0.0710* O rgan/Body Weight Ratio (g /1 0 0 g) Malea Fem ales 0.593 0.0279 0.636 0.0297 0.620 0.0287 , 0.686 0.0250 O rg an/B raln Weight Ratio (g/gl M ales Fem ales 1.81 0.0492 1.54 0.0625* 1.77 . 0.0560 1.77 0.0378* b U lM o oUt o> lo * O Uot a S ta tis tic a lly significant d iffe re n c e a t the 95 p e r c e n t confidence le v el. a i I < 1 1 i t i \ ftiUOUtf 'i I C T A B LE XXV TEST M ATERIAL; A ro clo r 1260 T w o-Y ear C hronic O ral Toxicity Study - Albino Rnta O rgan Weight and Ratio Data Six-Month Sacrifice Sum m ary of Mean Values Organ; H eart Dietary Level of 'A ro c lo r 1260 fppm) Control 1 10 ICO O rgan Weight <g> Males _ Fem ales 1.70 1.05 1.45 1.12 1.63 1.05 1.49 1.06 Organ/Body Weight Ratio (g/IOO g) M iles Fem ale. 0 .2 82 0.302 0.286 0.277 0.283 0.307 0.286 0.368** O IaJ con ot o ou* O Statistically significant difference at the 99 percent confidence level. O rg an /B raln Weight Ratio (g/gl M ales Fem ales 0.867 0.538 0.690 0.810 0.583 0.606 0.749 0.564 n * Lr TABLE XXVI TEST MATERIAL: A ro clo r 1260 'Two-Year Chronic O ral Toxicity Study - Albino R i t i Organ Weight and Ratio Data Six-Month Sacrifice Sum m ary of Mean Values Organ: Brain Dietary Level of A ro c lo r 1260 Ippml C o n tro l 1 10 100 Organ Weight Organ/Body Weight Ratio (g| (g /1 0 0 g) ( M a le s ______ F e m a l e s __________M a le s ______ F e m a l e s ________ Final Body Weights of S a c rific e d Rafts ' <gl M a l e s ______ F e m a l e s 1.96 1.95 0.320 0.560 613 348 2.10 1.92 0.412 0.474* 509 405 2.01 1.73 0.349 0.504 575 . 343 1.99 1.88 0.382 0.650* 522 289 t&bUOOi O * Statistically significant difference at the 95 p e rc e n t confidence level. -j o o cr 4 / ( t S l ^ -TEST sac. <*? c. Histopathologic Findings H istopathologic examination of tissu es and organs t a k e s f r o m a l l a n i m a l s f r o m b oth the co n tro l and 100 ppm groups was conducted. m T a b l e s XXVII and XXVIII l i s t a 11 his topa tholo gic c han ge s noted. All of the lesions noted in the m icroscopic examination of tissues w ere those of spontaneous disease and are not unusual for the a lb in o r a t . TTie m o s t fr e q u e n t findings w e re le s i o n s in the tr a c h e a and lungs, indicating chronic m urine pneumonia. These occurred in the eontr a s w ell as the r a t s fed A ro c lo r 1260. I ACM 0 C3 7 o 0 0( 303 r '' L r 43 e TABLE XXVII T E S T MATERIAL: A ro c lo r 1260 Tw o-Y ear Chronic O ral Toxicity Study - Albino Rats Histopathologic Changes Six-Month Sacrifice Group: Control N um ber oi Animals Organ Examined Findings Averaj Incidence ' Grade 5 Males Trachea Lung Liver Skeletal muscle Tracheitis Focal tracheitis Focal pneumonitis H yperem ia 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 H yperem ia H yperem ia Pericholangitis Focal inflammation 1 1.0 2 2.5 1 1.0 l 0.5 1 1.0 AU other tissues and organs were normal histologically. Grading System 0,5 a minim al 1.0 * slight 2 .0 'm ild 3.0 * moderate 4.0 * severe 5.0 extreme c: ACM OC37 00 309 tritai. / t a b l e xxviii T E S T M ATERIAL: A ro cio r 1260 T w o -T e a r C hronic O ral Toxicity Study - Albino Hats Histopathologic Changes Six-Month Sacrifice G ro u p : 100 ppm Number of Animals Organ Examined Findings Ave rag Incidence G rade 5 Males Trachea Lung Liver Tracheitis Focal tracheitis Focal pneumonitis H yperem ia H y perem ia Focal pericholangitis: 2 1 4 4 l 1. 2.0 0.5 1.0 1.5 1.0 0.5 5 Females Trachea Lung Liver Kidney Focal tracheitis Focal pneumonitis H yperem ia H yperem ia 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 w ere normal histologically. Grading System 0,5 m inim al 1.0 slight 2 .0 mild 3.0 m oderate 4.0 severe 5*0 extrem e AO* CC371 310 00 i aX 3 T E S T 50 3* T w e l v e - M o n t h S a c r i f i c e A, G r o s s Path olo gic r in d i n g a Gro** pathologic findings among test anim als were significantly different from those noted in control anim als. b. Organ Weight and Ratio Data The m e a n o rg a n w eight and r a t i o d ata c o lle c te d a t t; tw elve m onth sacrifice a re presented in Tables XXIX through XXXIV. . Statistically significant differences are designated by a ste risk s following the test group value. O r g a n w e ig h ts, o rg a n to body w e ig h t and o r g a n to bz weight ratios disclosed several randomly occurring intergroup differences The lack of any consistent dose related resp o n se and. the absence of any deleterious histopathologic change confirm that these differences w ere not re la te d to the ingestion of A roclor 1260. j,:o n n * ia 3 ooo Dietary Level (ppm) Control .1 10 too TA B L E XXIX TEST MATERIAL: A roclor 1260 Tw o-Y ear Chronic O ral Toxicity Study - Albino Rata Twelve-Month Sacrifice Organ Weight and Ratio Data Sum m ary of Mean Values Organ: Liver Org an Weight (el M ales Fem ales 22.1 15.5 17.1* 10.7# 20.0 13.6 2 8 . B* 14.1 O rgan/Body Weight Ratio ( f i / I OOg ) M ales Fem ales 3.79 3.52 2.79** 3.01* 3.30 3.54 4.26 3.79 O rgan/D raln Weight Ratio (g/g> M ales Fem ales to .a 7.72 9.23 5.76 10.8 7.2B 13.4* B. 52 ^ Statistically significant difference at the 95 percent confidence le v e l. S t a t is t ic a l ly sig nificant d if f e r e n c e at the 99 p erce n t confid en ce l e v e l . oi>*  Dietary Level (ppml Control 1 10 100 TA BLE XXX TEST MATERIAL; A roclor 1260 T w o-Y ear Chronic O ral Toxicity Study - Albino Rata Twelve-Month Sacrifice , Organ Weight and Ratio Data Sum m ary of Mean Values Organ; Kidneys O rgan Weight M ales (g) F em ales 4.04 3.84 3.19 2.58*4 4.00 2.78* 5.11 2.81 O rgan/Body Weight Ratio ( g /l0 0 g) M ales Fem ales 0.692 0.738 0.625 0.724 0. 660 0.736 0.758 0.755 O rgan/B rain Weight Ratio (g/g) M ales Fem ales 1.97 1.58 2.06 1,39 2.16 1.48 2.38* 1.69 Statistically significant difference at the 95 p ercen t confidence level. * Statistically significant difference at the 99 p ereen t confidence level. v o o ' L OO Dietary Level (ppm) Control 1 10 too TA*BLE XXXI TEST M ATERIAL: A ro c lo r 1260 T w o-Y ear Chronic O ral Toxicily Study - Albino Rata Twelve-Month Sacrifice Organ Weight and Ratio Data Sum m ary of Mean Valuea Organ: Spleen O rgan Weight (e) M ales F em ales 0.778 0.756 0.796 0.460 0.836 0.578 0.785 0.474 O rgan/D ody Weight Ratio (g/100 c| M ales Fem ales 0.133 0.183 0.122 0.129* 0.119 0.150 0.116 0.127 O rgan/B raln W eight Ratio (g/g) M ales Fem ales 0.380 0.408 0.457 0.365 0.396 0.247* * 0. 308 0.284 * O u> vo% Statistically significant difference at the 95 percent confidence le v e l. OoL-P ) O Dietary Level (ppm) Control 1 10 too o TABLE XXXII o TEST MATERIAL; A roclor 1260 T w o-Y ear Chronic O ral Toxicity Study - Albino Rata Twelve-Month Sacrifice Organ Weight and Ratio Data Sum m ary of Mean Values Organ; Gonada O rgan Weight (g) M ales F em ales 1.46 0.116 1.30 0. 101 1.51 0.112 4:01** 0.000 Organ/Body Weight Ratio (g/100 g) M ales Fem ales 0.596 0.0275 0.551 0.0287 0.570 0.0294 0.598 0.0218 O rg an /B rain Weight Ratio (g/gl M ales Fem ales 1.70 1.02 0.0574 0.0552 1.09 1.68 0.0564 0.0527 Statistically significant d ifference at the 95 percent confidence le v e l. * Statistically significant difference at the 99 percent confidence le v el. 3 O .vCl 8 bUUVM o Dietary Level (ppm) Control 1 10 100 o s TABLE XXXIII TEST MATERIAL: Aroclor*1260 T w o-Y ear Chronic O ral Toxicity Study - Albino Rata Twelve-Month Sacrifice Organ Weight and Ratio Data r Sum m ary of Mean Valuea Organ: Heart O rgan Weight (gl Malea Femalea 1.71 1.23 1.68 1.07 1.59 1.16 1.66 1.27 O rgan/Body Weight Ratio (g/100 g) Males Femalea 0.293 0.287 0.273 0.301 0.261 0.307 0.275 . 0.340 O rgan/B raln Weight Ratio - (g/g) Malea Females 0.635 0.611 0.902 0.575 0.845 0.620 0.866 0.760 4 ooo ' TABLE XXXIV TEST M ATERIAL: A ro c lo r 1260 Tw o-Y ear Chronic O ral Toxicity Study - Albino Rata Organ Weight and Ratio Data * Twelve-Month Sacrifice f Sum m ary of Mean Valuea Organ: Brain ________________________ ____________ _________________-- ----------------------- ---------------- .--------------------- ---:____________ _______ Organ Weight Organ/Body Weight Ratio Final Body Weight of Dietary Level (g) ( g /1 0 0 g) Sacrificed Rata (grams) (ppm) _ Males Females Males Females Malus Females | r V * Cont rot 2.04 2.02 0.149 0.460 584 .439 1 I. 87 1.86 0.304 0.522 616 156 o a 317 o tO a O vr> * o o - - AP to 1.88 0.110 0.491 too 2 . IS 1.67*4 0.118 0.449 Statistically significant difference at the 99 p ercen t confidence le v e l.1 607 385 675 172 -- Cr - c. H isto p a th o lo g ic Findings ' Histopathologic examination of tissues taken from each ra t s a c r i f i c e d f r o m the c o n tro l and 100 ppm g r o u p s a f te r twelve m o n th s o i testing w aj conducted. Tables XXXV and XXXVI lis t a ll hisopathologic changes noted. All of the lesions noted la the m icroscopic exam ination of tis s u e s w e re those of spontaneous d isea se and a re not unusual for the albino ra t. The m ost frequent findings w ere lesions in the trachea and lungs, indicating chronic m urine pneumonia. These occurred in the contr a s w ell as the ra ts fed A roclor 1260. AQH C03776 318 00C >o TABLE XXXV T E ST M ATERIA L; A r o c io r 1260 T w o-Y ear C hrom e O ral Toxicity Study - Albino Rata Histopathologic Changes Twelve-Month Sacrifice Group: Control N um ber o Animals 5 Males 5 Females Organ Examined TracheaLung U rinary Bladder Trachea Lung Colon Findings Incidence Tracheitis Chronie respiratory disease Calculus l 2 1 Tracheitis Chronic respiratory disease Parasites 1 b* 1 1 Ave Cr 1. 1. 1. 1. 1. 1. All other tisju es and organs w ere norm al histologically. Grading System 0 . 5 = minimal 1.0 = slight 2 .0 mild 3.0 3 moderate 4.0 severe 5.0 3 extrem e A0M CO3 77 7 3l9 00 BI - r S5 f 3Y TABLZ XXXVI TXST MATERIAL; A ro c lo r 1260 Tw o-Y ear Chronic O ral Toxicity Study - Albino Rita Histopathologic Changes Twelve-Month Sacrifice C ro u p : 100 ppm N um ber ol. . Animals Organ Examined 5 Males Trachea Lung Kidney Liver 5 Females T rachea Lung Findings Tracheitis Chronic resp irato ry dijease . Focal lymphoid infiltration V acuolar change of random cells Tracheitis Chronie respiratory disease Incidence 1 3 1 l 1 1 Ave r Gra< l.C l.C l.C l.C ' i:o 1.0 All other tissues-and organs were normal histologically. Grading System 0.5 a minimal 1.0 * slight 2.0 * mild 3.0 * moderate 4.0 * severe 5.0 * extreme ACM OC3778 OC 320 S I T S r bO . Final Sacrifice a. C r o n Pathologic Finding s G ro js pathologic findings among test animals were not significantly different from chose noted in control anim als. b. Organ Weight and Ratio Data The m ean organ weight and ra tio data collected at the final sac rifice a re presen ted in Tables XXXVII through XLII. Statistical!) significant differences a re designated by a s te ris k s following the te st group value. A bsolute liver weights and liv e r to body weight or liv e r to b r a in w eight ra tio s w e re sig n ifican tly elev ated in those r a ts fed 100 ppi A ro clo r 1260. O ther organ weights, organ to body weight and organ to b r weight ratios disclosed several randomly occurring intergroup difference: The lack of any consistent dose related resp o n se and the absence of any deleterious histopathologic change confirm that these differences were n o t r e la te d to the in g e stio n of A ro c lo r 1260 vono**^ ACM 0 C37 321 0( 3IO T c 5T 322 O iclary Level (ppm) ontrol 1 10 00 TA B LE XXXVI! ' T E ST MATERIAL* A ro c lo r 1260 T w o-Y ear C hronic O ral Toxicity Study - Albino R ata O rgan Weight and Ratio Data i Sum m ary of Mean Values Final Sacrifice Organ; Liver Org an Weight (B> Males* Fem ales 22.0 16. 3 22.0 16.6 24. 1 18. 1 29.9** 22. 7 Organ/lloity Weight Ratio (g/l00g) M ales Fem ales 3.47 3.05 3.40 3.35 2. 87 + 3.19 4.67** 4 .42* S ta tis tic a lly significant d iffe re n c e a t the 95 p e r c e n t confidence le v e l. SlaiislUBaity significant d ifferen c e a t the 99 p e rc e n t confidence le v el. r*> xoo Ui O O rg a n /B ra in We ight Ratio (fi/fil M ales Fem ales 10. 10 8.42 9.93 8.62 11.20 9. 26 13.40 11.60 )ictary Level (ppm) Control K 10 OO TABLE XXXIX TE ST M ATERIAL: A ro c lo r 1260 t T w o-Y ear Chronic O ral Toxicity Study - Albino Rata Organ Weight and Ratio Data f` Sum m ary o( Mean Values Final Sacrifice l j Organ: Spleen | _________________________________________ *____________________________________________________________________________________________________________________________________ V Organ Weight Organ/Body Weight Ratio O rgan/B rain Weight Ratio i M ales (el Fem ales in/too M ales Fem ales (e/gl M ales Fem ales 1. 15 0.96 0. IB2 0. 181 0.520 0.492 1. 17 0.72 0. 178 0. MB 0.529 0. 370 1.09 0.83 0. lit 0.142 * 0.509 0. 428 0.89 0.75 0.136 0. H6 0.400 0.379 00 cu o i IO X \ CJ Loou Oo Dietary Level fnpnil Control 1 10 100 ' TABLE XL TEST M ATERIAL: A ro clo r 1260 Tw o-Y ear Chronic O ral Toxicity Study - Albino Rata Organ Weight and Ratio Data i Sum m ary of Mean Values Final Sacrifice Organ Weight M ales (g) Fem ales 2.52 0. 123 3.56* 0. 140 3.36 0. 177 Organ: Gonads Organ/Body Weight Ratio l e / i o o g) M ales Fem ales 0. 397 0.0222 0.550* 0.0317 0. 400 0.0338 2.97 0. 113 0. 464 0.0229 > S ta tis tic a lly s ig n ific a n t d iff e r e n c e a t the 95 p e r c e n t co n fid en ce le v e l. o O rg a n /fratn W eight Ratio <g/g) M ales F em ales 1. 15 0.0628 1.61* 0.-071 8 1.56* 0.0900 1.33 0.0584 ,2E JO 97t)UUU.l AOH 003782 ^- '"Jv Dietary Level (ppm) Control 1 10 100 TABLE XL! T E ST M A TER IA L: A ro c lo r 1260 T w o-Y ear Chronic O ral Toxicity Study - Albino Rata O rgan Weight and Ratio Data l Sum m ary of Mean Values Final Sacrifice Organ: Heart Organ Weight (g) M ales Fem ales 1.87 1.54 1.98 1.45 1.90 1.58 O rgan/Rody Weight Ratio ( g/ I OOg) M ales Fem ales 0.294 0. 288 0. 304 0. 294 0 . 225S* 0.279 2.00 1.49 0.313 0.288 O Statistically significant difference at the 99 p ercent confidence level. tuo* n> at oo O rg an /B rain Weight Ratio (g/g) M ales F em ales 0 . 860 0.795 0.893 0.747 0.884 0.809 0.904 0.764 .S b U U U i CO c. Histopatholocic Findings Histopathologic exam ination of tissu es and organs ta k en f r o m a ll a n im a ls s a c rif ic e d a fte r 24 m o n th s on te st was conducted T a b le s' XLIII th ro u g h XX.VI l i s t a ll h isto p a th o lo g ic cha: noted.' Table XLVU contains the re su lts of the histopathologic examinat: of the u rin a ry bladders. S ig n ific an t li v e r in ju r y w a s found in a n im a ls fed 100 po Ax o cl o r 1260 (T -IIH . The compound a s s o c ia te d le sio n s consisted of vact. change, focal h y p ertrophy and focal h y p e rp la sia . In addition, th e re w e n le sio n s of inflam m ation, n e c ro s is , fib ro sis and m in o r deg en eratio n in thi g ro u p w h ich , alth o u g h s e e n in the c o n tr o ls an d lo w e r t e s t g ro u p s , w e r e rr se v e re and frequent in the T-II1 group. The vacuolar change was not seen in the control animal: b u t w a s o b s e r v e d o c c a s io n a lly in l iv e r s f r o m T - I (lp p m ) and T -H (10 ppm a n im a ls . It w as frequent in the T-IH a n im a ls . This lesion is m orphologi indicative of fatty degeneration. F o rm a lin -fro z e n sections of liv e rs from re p re se n a tiv e anim als which displayed vacuolar changes were stained witi O il Red 0 to re v e a l the p resen ce of fat. The v a c u o la r lesion in the cytopla of the so cells was positively identified as fat. The hypertrophic change found in the liver was focal and Often lim ited to the cen tral lobular a re a w here groups of cells w ere swolle to two or th re e tim es th e ir norm al size with c le a r pink homogenous cytopla The h y p e rp la sia was associated with the sam e cells and appeared to be an Fin A0 9 8 ACM CO 3754 0 1 326 WO extension of the hypertrophic lesion. The h y p erp lastic cellj v e re also usually hypertrophic. The m ost severe exam ples of hyperplasia appear a s nodular grow ths with lim ited com pression of the surrounding n o rm a l hepatic tissue. The m inor lesions of degeneration, hepatitis, ductule c p ro liferatio n , n e cro sis and focal lymphoid in filtratio n seen in the contro an im als and the T * Ian d TH groups are lesio n s of spontaneous disease a a re not related to the A roclor 2260. This level of liv er disease is not un in old anim als. H yperplasia of the u rin a ry b la d d er was found In an anin fro m the control group. This finding was not p re s e n t in any of the ra ts U A ro c lo r 1260. All of the other lesions in other tissu e s found in these a n i a r e related to spontaneous disease and they a re not unusual for old ra ts . J 7 jf Donovan C o rd o n , C. V. M . , P h . D. D iplom ate, A m erican College of V eterinary Pathologists O F,0 0 0 9 4 9 ACM CC3 7 327 oc c n . Dietary Level (ppm) Control 1 10 100 TABLE XLII T E ST M ATERIAL! A ro c lo r 1260 T w o-Y ear C hronic O ral Toxicity Study - Albino Rata O rgan Weight and Ratio Data i Sum m ary of Mean Values Organ Weight <g) M a le s ________F e m a l e s Final Sacrifice Organ; Drain Organ/Dody Weight Ratio (g/IOOg) M a le s _______ F e m a le Final Body Weight of Sacrificed Animals (gram a) M ale s________ F e m a l e s 2. IB 2.21 2. 15 1.95 1.94 1.96 0. 342 0. 343 0.255** 0. 362 0.407 0.347 642 654 845** 551 525 584 2.22 1.95 0.346 0. 378 641 644 l C I t I I I l II % i OSbUUUj O o UK)J CO S tatistically significant difference a t the 99 p ercen t confidence level. ADH 00370b tr o Number of A nim als 11 M a le s r*\ 3 __________ . i2n5 1 O O K> vO o O o u> Oi TARLE XLIII TEST MATERIAL: A roclor 1260 Tw o-Y ear Chronic O ra! Toxicity Study - Albino Rata Histopathologic Changes Final Sacrifice Group: Control Organ Examined H eart Trachea Ljng Liver Stom ach Spleen Kidney Testes Prostate Adrenal Gland B rain Eye Findings Chronic focal m yocarditis Tracheitis Chronic respiratory disease Focal degeneration Ductile hyperplasia Chronic gastritis Hem osiderosis Chronic nephritis Testicular degeneration Periarteritis Inflammation Telangiectasis Nodular hyperplasia Focal fatly change Focal encephalitis Inflammation Incidence 3 3 9 1' 2 1 3 8 2 2 1 1 1 1 1 2 o A verage G rade 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 O TABLE XLIII continued TEST MATERIAL: A ro clo r 1260 3Iu *T cS7 T w o-Y ear Chronic O ral Toxicity Study - Albino Rata Histopathologic Changea Final Sacrifice Group: Control Number of A n im a la ________ O rg a n E x a m in e d _________________ F in d in g s 14 F e m a le s Heart Trachea Lung Liver X) in to o r~ > U) u> o o *r o o Ui --1 rD CD Stomach Colon Spleen Uterus Kidney Ova ry Adrenal Gland Salivary Gland All ot h er t i s s u e s and o r e a n s n* nn nn ^l Chronic focal m yocarditis Tracheitis Chronic respiratory disease Focal lymphoid infiltration Ductile hyperplasia Focal hepatitis Non-lipid vacuolar change Chronic gastritis Acanthosis - squamous epithelium Parasites H em osiderosis M etritis Chronic nephritis Focal lymphoid infiltration Cyst Telangiectasis Nodular hyperplasia Chronic librosis and atrophy t i .. A verage In c id e n c e _______________ G r a d e 7 2.0 9 1.0 13 1 . 0 3 1.0 2 1.0 1 1.0 2 0. s 3 1.0 5 1.0 1 1.0 4 1.0 3 2.0 6 1.0 1 1.0 1 1.0 9 1.0 4 1.0 1 1.0 % * o-I 331 Number of Animals II Males A 5 2 2 y\ > o tx oo TABLE XLIV T E ST M ATERIAL! A ro c lo r 1260 Tw o-Y ear Chronic O ral Toxicity Study - Albino Rate Histopathologic Changes Final Sacrifice Group: I ppm * Organ Examined Heart Trachea Lung Livor Pancreas Stomach Spleen Lymph Node Kidney Testes Prostate Semina* V esicle Findings Chronic focal m yocarditis Tracheitis Chronic respiratory disease Focal hepatitis Focal scarring H em osiderosis Chronic focal pancreatitis Acute focal g astritis H em osiderosis Congestion Chronic nephritis Testicular degeneration P e ria rte ritis Inflammation Inflammation , Incidence 4 7 101 1 1 2 11 1 7 1 2 4 1 A verage Grade 1.0 1.0 2.0 1.0 1.0 !.0 ` 1.0 31..00 1.0 2.0 2. 0 1.0 2. 0 2. 0 ~Y- * r Number of Animals 11 M a le s TABLE XLIV continued T E S T M A TER IA L: A ro c lo r 1260 Tw o-Y ear C hronic O ral Toxicity Study - Albino R ata Histopathologic Changes Final Sacrifice Group; I ppm * Organ Examined Adrenal Gland Findings Nodular hyperoplasia Focal fatly change Incidence 2 2 14 F e m a l e s H eart Trachea 2 Lung 2 O o Liver Stomach 332 oX ------------- -----o o Chronic focal m yocarditis Chronic focal m yocarditis 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 A verage Grade 1.0 .1.0 1.0 3.0* 1.0 1.0 1.0 1.0 0. 1.0 2. 0 1.0 1.0 ooo 333 K.nno955 Q Number of Animals H Fem ales c ooi*> -40 TABLEXLIV continued TE ST M ATERIAL: A ro c lo r 1260 Tw o-Y ear Chronic O ral Toxicity Study - Albino Rale Histopathologic Changes Final Sacrifice Group: I ppm ' Organ Examined Stomach Colon Spleen Lymph Node Kidney Uterus Adrenal Gland Findings Ulceration and acanthosis Parasites Hemosiderosis H y p erplasia Congestion Chronic nephritis Vacuolar change (fatty) M etritis Telangiectasis Nodular hyperplasia Congestion Incidence 1 1 11 I 1 3 1 4 9 3 1 All other lis a u c i and organa w ere n o rm al histologically. 0. 5 = minim- I Grading System Sn A verage G rade 1.0 1.0 1.0 1.0 1.0 2. 0 . 1.0 1.0 1.0 1.0 1.0 E.EOO Number of Animals 7 Males 2 5 5 ffi TABLE XLV TE ST M ATERIAL: A ro clo r 1260 T w o-Y ear Chronic O ral Toxicity Study - Albino R ats Histopathologic Changes Pinal Sacrifice . G ro u p : 10 p pm * Organ Examined H eart Trachea Lung Liver Stomach Spleen Kidney Prostate Adrenal Gland Findings Chronic focal m yocarditis Tracheitis Chronic respiratory disease Suppurative pneumonia Vacuolar change (fatty) Chronic gastritis Acanthosis H em osiderosis Chronic nephritis Inflammation Nodular hyperplasia Incidence 3 2 5 1 2 1 2 3 6 2 1 14 F e m a l e s ti Heart Trachea Lung Chronic focal m yocarditis Thracheitits Chronic respiratory disease 3 8 14 A verage G rade 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 r t TABLE XLV continued T E ST M A TER IA L: A ro c lo r 1260 T w o-Y ear Chronic O ral Toxicity Study - Albino R ate Histopathologic Changes Final Sacrifice m C/l 'r3"i*7Tvcr- G ro u p : 10 p p m ' Number of Animals 14 F e m a l e s n x O CD ooU-Ji 335 iu Organ Examined Liver Pancreas S tom ach Spleen Kidney Uterus Pituitary Adrenal Gland - Findings Vacuolar change (fatty) Focal hyperplasia Chronic focal pancreatitis P e ria rte ritis Acanthosis H em osiderosis Chronic nephritis M etritis Congestion Telangiectasis Nodular hyperplasia Congestion A verage In c id e n c e ______________ G r a d e 1 1 1 1 1 12 10 . 7 1 7 I 1 1.0 1.0 3.0 3.0 1.0 1.0 1.0 2.0 1.0 1.0 1.0 1.0 All other tissu e s and organs w ere n o rm al histologically in rr~ TABLE XLVI T E S T M ATERIAL: A ro c lo r 1260 T w o-Y ear Chronic O ral Toxicity Study - Albino R ats Histopathologic Changes Final Sacrifice G ro u p ; 100 ppm Number of A n im a ls ________ O r g a n E x a m in e d 10 M ales H eart Trachea Lung Liver * gbuuw i O O Uuai\ o o uo> i. Pancreas Stomach Spleen Kidney 1 Findings Chronic focal m yocarditis Tracheitis Chronic respiratory disease Congestion Vacuolar change (fatty) Focal degeneration Congestion Cent rolubular hypertrophy Telangiectasis Chronic focal pancreatitis Inflammation Acanthosis 1lumottide r o s i s Focal lymphoid Infiltration Calcified concretions in pelvis Incidence S 8 9 1 2 1 3 2 1 2 2 2 7 1 1 Average G rade 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 r r' Number of Animals 10 M ale s TABLE XLVI continued T E S T M A TER IA L: A ro c lo r 1260 T w o-Y ear Chronic O ral Toxicity Study - Albino Rata Histopathologic Changes Final Sacrifice G ro u p : 100 ppm* Organ Examined Kidney (continued) Testes Prostate Thymus Adrenal Gland . Findings Calcified concretions in pelvis A apcrm ia Inflammation Cyst Telangiectasis Nodular hyperplasia Incidence 1 1 1 1 3 1 ^ t i U : f6 IS F e m a le s O o to -- >o X oo H eart Trachea Lung Liver Chronic focal m yocarditis Tracheitis Chronic respiratory disease Congestion Edema Vacuolar change (fatty) 5 a h ! 1 5 ) o I > I ' A verage G rade 1.0 1.0 I. 0 1.0 1.0 1. 0 t Ii l i ( ti % I 1.0 1.0 1.0 1.0 1.0 1.0 -o 09bUUU)l Number of Animals IS F em ales i ! 1 | > 1 ooUi u> on CO TABLE XLVI continued T E ST M ATERIAL: A ro c lo r 1260 Tw o-Y ear Chronic O ral Toxicity Study - Albino R ats Histopathologic Changes Pinal Sacrifice G roup: 100 ppm* Organ Examined Liver (continued) . Pancreas Spleen Kidney Uterus Pituitary Adrenal Gland Parathyroid Findings Focal hyperplasia Chronic inflammation of liver capsule Cenlrolohular hypertrophy N ecrosis Uuclile cell hyperplasia portal fibrosis and widespread eosinophil inclusions in hep.itocyte cytoplasm Chronic fucal pancreatitis and periarteritis H em osiderosis Chronic nephritis M etritis Congestion Telangiectasis Nodular hyperplasia Congestion Hype rplasia Incidence 4 1' 5 l 1 1 9 a 7 1 6 1 1 1 All ni l. * - i " -- -------- 1 ------ O A verage G rade 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 yK r r o Group C T-l * (1 ppm) T-1I (10 ppm) T-.lll (100 ppm) o Ya BLE XLV1I T E ST M ATERIAL: A ro c lo r 1260 Tw o-Y ear Chronic Oral Toxicity Study - Albino Rats Histopathologic Changes of the U rinary Bladder Final Sacrifice Humber Sex Examined Findings* Incidence M 11 F 14 P ro tein aceo u s plug (34) Focal epithelial hyperplasia (62) 1 1 M 10 F 11 P r o te in a c e o u s plug (B6# 105, and 107) None 3 - M7 F 14 P roteinaceous plug (187) None 1' - M 10 F 14 P roteinaceous plug (271) None 1 - iSbUUUl * Individual animal num bers a re shown in parentheses. CD "` ^ utoi ox oou> Gradini S y s t e m 1 . 0 - minimal or trace 4 . 0 - severe 2.0 s mild 5.0 = extreme 3.0 = moderate A verage G rade 1.0 '- - jma**; , OIW " I S W* C. D etailed D escription of Tum or Fir, dines T un\or data fop individual anim als including location* weight and p a th o lo g ic c la s s ific a tio n ape p re s e n te d in T a b le s XLVIII through LI, Nona of these tum ors could be re la ted to the ingestion of Aroclc 1260 and a r e co nsidered n orm al for a ran d o m population of ra ts this age 1000962 aOM 0 0 3 Of 340 o Animal l.'umbcr mi Sex Location 1- M Abdomen 2-M Pancreas ^J6-F W7` F . S 8*F 50-F Abdomen Lymph node 1 Abdomen Abdomen 52-F Ui 39-F , ; ' % o J M -F ^ Abdomen Abdomen Adrenal gland Abdomen o I TABLE XLVIII TEST M ATERIAL: A roclor 1260 T w o-Y ear Chronic O ral Toxicity Study - Albino Rat* Description ol Tum or Findings Group: Control W eight (gram s) 11.76 64.98 35.09 " - - 88.92 Size (cm) 8x1x2 5x2x2 2x2x1 2x2x3 * 1 U 11 ~ A C lassificatio n M amm ary fibroadenoma A denocarcinom a M am m ary fibroadenoma , M am m ary fibroadenoma Reticulum cell sarcom a M am m ary fibroadenoma M am m ary fibroadenoma M am m ary fibroadenoma M am m ary fibroadenoma Phcochrom ocytom a CllVA & i it M onths on Test 24 24 24 24 24 7 24 24 fcKiUUU* o Animal Number and Sex 9 9 -M 127-F 128-F 138-F 141-F 151 - F Ui 1 5 2 -F M r*>* T o Location Pituitary Pituitary Abdomen Pituitary Abdomen Abdomen Pituitary Ovary Abdomen Abdomen TABLE XLIX * TEST M ATERIAL: A r o d o r 1260 Tw o-Y ear Chronic O ral Toxicity Study - Albino Rate Description o Tum or Findings ' Weight (gram s) - Group: 1 ppm Size (cm) - C lassificatio n ''Chromophobe adenom a 25.00 .60., 80**' 6x3x1 5x6 x 2* / Chromophobe adenoma 1 M ammary fibroadenoma i t Chromophobe adenoma ^ M ammary fibroadenoma 20.07 M a m m a ry fib ro a d e n o m a - Chromophobe adenoma * - "'Adenoma 14.89 540.00 13 x 15 x 2 * M a m m a r y fib r o a d e n o m a Mammary fibroadenoma M onths on Test 20 24 21 i* *24 24 24 22 oV S9t>uuu.i. Animal Number and Sex 205-F 200-F 213-F 216-F 220-F 221-F fc. L J fe r x TABLE L TEST MATERIAL: A roclor 1260 Tw o-Y ear Chronic O ral Toxicity Study - Albino Rata Description of Tum or Findings G ro u p : 10 ppm Location Weight (grams) Abdomen 190.00 Pituitary - Abdomen - Right shoulder 138. 00 Abdomen Pituitary 9.57 - Submaxlllary region Abdomen 14.44 29.0 Sixc (cm) 9x5x4 - . 2x3x1 3x5x2 C la ssific a tio n ^ M amm ary fibroadenoma (C h ro m o p h o b e a d e n o m a j M amm ary fibroadenoma , k Subcutaneous tum or `'M a m m a ry fibroadenom a * Chomophobe adenoma i Fibroadenoma M ammary fibroadenoma O M onths on Teat 24 24 24 23 24 24 < 1<(009Mj oo Animal Number and Sex V 22m- F 233-F 234-F Location Left fem oral region Pituitary Abdomen Panereas TABLE L continued TEST MATERIAL: A ro clo r 1260 Tw o-Y ear Chronic O ral Toxicity Study - Albino Rata Description of Tam or Findings G roup: 10 ppm Weight (gram s) 56.00 Size 6x8x2 Classification t/S u b c u ta n e o u s tum or 60. 82 6x4x3 K Chromophobe adenoma M ammary fibroadenoma t'Islet cell adenoma u u> oX o o Ut i 0 \ \ 1 I M onths on Test 6 24 24 s sv i' Animal Number and Sex 244-M Location Pancreas 264-M Paneres 281 - F Abdomen 293-F Liver 294-F 3 0 1 ,F. Abdominal cavity Liver 3 TABLE LI TEST MATERIALI A r clo r 1260 Tw o-Y ear.C hronic O ral Toidcity Study - Albino Rata Description ol Tum or Findings G roup: 100 ppm Weight (gram s) 35.04 50.75 _ Size (cm) -* ` 6x4x2 6 x 4x 3 - C lassificatio n 1 Adenoma '''Islet cell adenoma / M ammary fibroadenoma Lymphoa a re orna Fibrom a L ym phosarcom a M onths on Test 24 21 24 23 24 23 II Animal Number and Sex 1302-F 308-F ' 311 - F Location Lymph node Pituitary Abdomen 312-M 314-F , .j Z2 Pituitary Abdomen; ACo D TABLE LI continued TEST MATERIALS A roclor 1260 Tw o-Y ear Chronic O ral Toxicity Study - Albino Rata Dcacrlption ol Tumor Findings G ro u p ; 100 ppm *1 W eight (gram s! 14.00 26.00 Sire ______(c m ) _______________ C l a s a l f i c a t l o n - ^'Lym phosarcom a - k'C hromophobe adenoma 4x3x2 1x2x1 'Mammary fibroadenoma , iM am m ary fibroadenoma - ''Chrom ophobe adenoma 5x4x3 ^ M am m ary fibroadenoma M onths on Teal 24 24 24 24 24 d B K TEST REPORT-TO MONSANTO COMPANY TW O-YEAR CHRONIC ORAL TOXICITY WITH AROCLOR 1254 IN ALBINO RATS NOVEMBER 12, 1971 EBT NO. B7298 L Introduction At the re q u e st of M onsanto Company, a tw o -y e a r chronic o ra l toxicity study was conducted using albino ra ts to d eterm ine the potential toxicity of A ro c lo r 1254, Lot No. AK-38. The following re p o rt re p re s e e the resu lts of this investigation. e ACM 0035 00 347 M itd 'te L ' B IC J T 5 T 2 H. Sum m ary i A tw o -y ear chronic toxicity study was conducted using albino ra ts fed d ie ts c o n ta in in g 1 (T -I), 10 (T-II) o r 100 (T -III) ppm A r o c lo r 1234. F o o d c o n s u m p tio n w a s not a l t e r e d in any t e s t g r o u p . Body weight g a in s 1\ ' of t e s t a n d c o n t r o l a n im a ls did not d iffe r a f t e r 3 o r 12 m o n th s of te s t in g . { A f t e r 24 m o n th s f e m a le s fed 100 ppm A r o c l o r 1254 had gained l e s i w e ig h t , , than the c o n tro l fe m a les. Weight gains of the m ale ra ts did not d iffer i f r o m the c o n tro ls . The num ber of an im als dying and the time at w hich deal o ccu rred did not differ among test and control groups. i H em atological and clinical blood chem istry studies conducted after j i 3, 6, 9. 12. IS. or 24 months did not re v e a l any affects re la ted to A ro c lo r I 1254. U rin e a n aly se s failed to re v e a l any d ifferen c e betw een te st and -control rats. A t s a c r i f i c e a f t e r 3. 6, o r 12 m o n th s on t e s t , o r g a n w e ig h ts , o r g a n to i body weight and organ to brain weight ratio s d isclo sed sev e ra l random ly occurring m tergroup differences. The lack of any consistent dose related re sp o n se and the absence of any d eleterious histopathologic change c o n firm that these d ifferen ces w ere not related to the ingestion of A roclor 1254. A t the final s a c rific e a fte r 24 m onths on te s t , the absolute liv e r weight, and liver to body weight or brain weight ratios w ere significantly elevated In b o th T - I l l m a le s and fe m a le s . H isto lo g ic e x a m in a tio n s of the l i v e r s f r o m the T - U I g ro u p re v e a le d s e v e r a l a n im a ls v. tlh v a c u o la r ch an g e. ; i , M FonnwTO ADM 00 341' oc 348 .-- 2 !0 * - S T JsJ+yviLyuAU ?*uz. T h is le s io n is m o rp h o lo g ic a lly indicative- of fa tty d e g e n e ra tio n . S p e c ific ! f a t s ta in s c o n f ir m e d the p r e s e n c e of fa t in th e s e v a c u o le s . F o c a l h y p e r t r o and focal h y p e rp la sia w ere also found in the liv e rs from anim als fed A r o c lo r 1254. H y p e rp la sia of the u rin a ry bladder was found in anim als from the eontr g r o u p and f r o m e ae h of the te s t g ro u p s . T his h y p e r p la s ia w as u s u a lly associated with cystitis. Hone of the tu m o rs found could be re la ted to the ingestion of A ro c lo r 1254 and a r e co n sid e re d n o rm a l for a random population of ra ts th is a g e . i I i Respectfully submitted, INDUSTRIAL BIO-TEST LABORATORIES, INC. R ep o rt p re p a re d by: P h ilip Si. S m ith , B .S . A ssistant Toxicologist Rat Toxicity R e p o rt approved by: Jarhes B. Plank Senior Group Leader Rat Toxicity & / / J /P aul L. W right, Ph. D. Section Head, Toxicology j *.- __- _ ~ Ml L. K c p lm p u r, Ph.^> Manniiirr. Toxieulogy N o vem ber 12, 1971 bb:hp 1,000971 AOM 0C3 34 9 oc 1 3 I 0 T E S T y ia & L c i. j* c . 4 III* P ro c e d u re A. E xperim ental Animals The anim als employed in the teat w ere C harles River S train 3 a lb in o r a ta . P o u r hundred ra ts (200 m ale and 200 fem ale) w ere s e le c te d fo r the e x p e rim e n t, ear-p u n ch ed with the anim al num ber assigned and boused individually in standard w ire-bottom ed steel rat cages. Each cage bore a c o lo r-c o d e d card identifying the ra t w ith re sp e c t to p ro je c t num ber, d ietary level assignm ent, individual num ber and sex. B. O r g a n iz a tio n of G roups A s t r u c t u r a l outline of the e x p e r i m e n t is g iv e n in T able I* TABLE I TEST MATERIAL; A ro c lo r 1254 T w o-Y ear Chronic O ral Toxicity Study - Albino Rats Outline of E x p e rim en t Groun N um ber of A n im als Male Fem ales Dietary Level (oom) Control 50 50 None A d m in istered T -l T-U T -n i 50 50 50 50 50 50 l 10 100 * Charles R iver Breeding L aboratories, North Wilmington, M ass. R )n n n 7 2 n no354i 350 0 BIG TEST ^ 5 C. D i e t s F e e d i n g and Food Consumption A ll d ie ts w ere p re p a re d in the c e n tr a l d iet room of this laboratory. The basic ration from which all diets were constructed w a s a s t a n d a r d , p u lv e r iz e d sto ck r a t r a t i o n - . T h e d ie t fo r any given t e s t ( group was p re p a re d by blending the calc u la te d am ount of A roclor 1254 i w ith a pre-w eig h ed portion of the stock ratio n in a H obart m ixer. 1 F r e s h diets were prepared eaeh 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 everyi group w eekly for. the fir s t th re e months and m onthly for the next nine months. T hereafter, periodic spot cheeks were made. D. Body W eights and V"eight Gains i i i i | -i In itially , the body weight of each r a t in every group was d e ter j I mined and recorded. T hereafter, individual weighings w ere made w eekly | f o r the f i r s t 13 w e e k s and m o n th ly t h e r e a f t e r u n til the co n clu sio n of the investigation. t { E. M ortality and Reactions Checks for m ortality and abnorm al behavioral reactions w ere m ad daily throughout the investigation. "* F . H e m a to lo g ic Studies anH U rin e A n a ly s e s j fI Blood studies, including determ inations of hemoglobin concentra- 1 I tion, h e m ato crit value, erythrocyte count and both total and differential * P u r in a Rat Chow. R alston Purina Co. St. Louis. Mo. F r o w n s AO* 0C3 O' 351 6 leukocyte counts, w ere conducted upon five m ales and five fem ales from b o th the c o n t r o l and 100 ppm g ro u p s . e U rihe analyses for the presence of glucose, albumin, m ic ro scopic e le m e n ts , and d eterm inations of pH and specific gravity w ere c o n ducted upon urine sam ples at the same tim e intervals and from the sam e u iim als as those employed for the blood studies. . T h e s e s tu d ie s w e re conducted a f t e r 3, 6, 9 , 12, 18, and 24 months of feeding. G. C linical Blood C hem istry Studies D eterm inations of blood u rea nitrogen concentration (BUN), J | j i ! serum alkaline phosphatase activity (SAP), fasted blood glucose concen tration and seru m glutam ic-pyruvic tran sam in ase activity (SGPT) w ere conducted a f te r 3, 6, 9, 12, 18, and 24 m o n th s of feeding upon the s a m e ra ts as w ere the routine blood studies. H. P a th o lo g ic Studies When an anim al succumbed during the te st period, a gross autopsy was perform ed. In those case when postm ortem autolysis was not ad vanced, rep resen tativ e tissues w ere taken and preserv ed in ten percent ` form alin solution for possible future histopathologic study. 1 i A f t e r 3, 6 , and 12 m o n th s of te s t i n g , fiv e a n im a ls of each sex f r o rr each group w ere sacrificed and subjected to com plete gross pathologic exam inations. A bsolute organ weights wore re c o rd ed and organ to body weight i and organ to brain weight ratios computed. The following organs were Fonofm ACM 003 0 l 352 a I O T ST 2^ / included: liver, kidneys, spleen, gonads, heart and brain. These data w ere then subjected to statistical analysis. An A nalysis of Variance was conducted first and significant effects disclosed by that treatm ent w ere f u r t h e r s tu d ie s b y Mt M- t e s t s . Com plete m icroscopic examinations w ere conducted upon the t i s s u e s and o r g a n s f r o m a ll c o n tro l and 100 p p m g r o u p a n im a ls s a c r i f i c e d j a f t e r 3, 6, o r 12 m o n th s of te s t in g . The fo llo w in g t i s s u e s and o rg a n s w ere included in the exam inations: heart, tra c h e a , lungs, liver, p an creas, esophagus, stom ach, sm all intestine (duodenum, jejunum and ileum), caecuri colon, spleen, lymph nodes, kidneys, urinary bladder, gonads, prostate gland, sem inal vesicles, uterus, pituitary gland, adrenal glands, salivary glands, thyroid gland, parathyroid glands, skeletal m uscle, sternum , \ bone, perip h eral nerve, spinal cord'and brain (cerebrum , cerebellum and pons). The aforem entioned tissues were p repared and stained with Hematoxyiin-Eosin stain. e A fter two years of feeding, all surviving anim als w ere sacrificed and subjected to complete gross pathologic examination. T he absolute w eights of the liv e r, k id n e y s, s p le e n , gonads, h e a r t 1 and brain w ere recorded immediately after sacrifice. M icroscopic examinations were conducted upon tissues and organs from selected anim als dying during the experim ent and upon all anim als from the final sacrifice. KnniW75 AC* 0C3S n r 353 Xm l D I V T E S T 3 T issu es and organs examined w ere the sam e as those previous m entioned. i t L . T um or Incidence and C lassification tabulation of the incidence of tum or fo rm atio n in each group w a s m a d e a t the c o n clu sio n of the in v e s tig a tio n . In a d d itio n , tu m o r d a ta for individual anim als including location, weight, size and pathologic classification were recorded. Ii i i in n o v e ACW C03551 354 0( 3` \ Z 3 I 7 IV . Resulta A , Bodv Weights and Weight Gains The m ale and fem ale body weight data a re assem b led in Table II. The data in this table also Include the 3. 12 and 24 month total weight gains. 1000977 acm 0C355j 355 Of r\ o Dietary Level of A ro c lo r 1254 (ppm) Sex Control M F 1M F 10 M F 100 M F O o >O a uL>n o\ o o u ui U1 UI o T A D L E II T E S T M ATERIA L; A ro c lo r 1254 TW o-Year Chronic O ral Toxicity Study - Albino R ats Body Weight and Total Weight Gain Data Sum m ary of Mean Values 0 1 2 34 Body Weight (gram s) Week: 56 78 9 10 1 1 12 13 J33 203 245 313 362 373 391 409 424 440 440 449 467 474 136 ITS 190 219 244 254 259 265 270 276 281 278 290 288 133 206 253 322 364 373 396 425 4 36 457 470 483 490 509 136 171 190 213 235 246 248 250 259 270 270 274 279 2H5 133 209 25! 325 375 394 402 410 432 453 470 488 494 508 136 171 194 220 2 4 3 263 2119 293 281 272 276 274 260 286 133 207 260 324 365 375 295 419 428 440 450 469 480 486 136 174 197 223 242 254 276 290 2UI 268 270 274 277 280 90 - Da y Total Weight Ga in (ft r a n t s / r a t ) 3 11 152 376 119 376 152 353 114 r O Dietary Level of A ro c lo r 1254 (p">m) Sex Control M F 1M F 10 M F 100 O M F utn> CfcDX o o 4 498 297 522 289 529 300 495 292 O T A B*L Ei II continued T E ST MATERIAL A ro c lo r 1254 Tw o-Y ear Chronic Oral Toxicity Study - Albino Rata Body Weight and Total Weight Gain Data Sum m ary of Mean Values 56 nly Weight (grama) Month; 7 8 9 10 II 533 565 593 622 642 667 688 310 322 333 315 359 374 383 550 581 604 633 658 680 715 295 307 322 333 340 354 367 567 593 . 621 642 667 681 700 308 321 330 341 354 367 380 521 541 562 586 608 627 642 300 306 316 321 326 332 340 12-Month Total Weight Gain 12 ( g r a m s / r a l ) 701 568 390 254 72S 592 380 244 726 593 392 256 664 5 3 | 347 211 c o dietary Level of ' A r o c l o r 125-1 fp;m) Sex Jonttol M F 1M F io 3 M 100 M F M F * T A B L E II contin ued T E S T MATERIAL A ro c lo r 1254 Two-Year Chronic Oral Toxicity Study - Albino Rote Body Weight and Total Weight Gain Data Sum m ary of Mean Values 13 14 15 16 Body WeightL (grams) Monlli; 17 IH 19 20 21 22 23 24- Month Total Weight Gai \ 24 ( g r a m s /r a l ) 728 746 759 768 769 767 760 7 58 739 7 26 6 87 6 4 2 426 444 466 4 HI 500 515 533 547 551 550 564 551 509 415 760 780 807 800 802 795 786 769 750 728 715 656 401 426 476 483 493 510 521 532 537 542 55 3 540 746 774 824 780 804 ` 826 B23 B2I 813 800 767 762 421 433 485 466 475 4U1 485 492 2 9 8 . 500 471 50 0 523 404 629 364 6EB 714 735 730 733 726 716 700 6B5 652 6 28 65 6 360 367 392 374 381 394 393 398 401 400 395 411 523 275 ^ l> S t a t i s t i c a l l y s ig n ifi c a nt at the 99 p e r c e n t c o n f id e n c e l i m i t . LL0nJ0 AOH 0 0 3 5 5 5 4 B. Food Consumption The data obtained from the food consumption m easurem en ts c o n d u c t e d d u r i n g the f i r s t 12 m o n t h s of feeding i r e s u m m a r i s e d in T a b l e HI. T h e s e data re v e lle d no significant difference between test and control rats. The periodic checks conducted during the rem ainder of the investigation also revealed no outstanding differences between te st and control animals. O EnnmRg A" CCJ55e OC 359 oo o T A B LE If! T E ST MATERIAL: A ro c lo r 1254 Tw o-Year Chronic Oral Toxicity Study - Albino R ati Food Consumption Data 1 03 O --i m in Summary of Mean Values U Dietary Level of Aroclor 1254 _____ top n)______ S e x 1 Food Consumption (gram s/rat/seven days) Week: 56 7 89 Average Food p Consumption v 10 11 12 13 (flrn a / r a t / s e v e n d a y alft Coni rot M F 94 73 160 140 175 144 163 107 137 104 137 133 225 208 197 154 204 165 188 151 191 146 194 150 196 151- 174 HO M F 112 87 148 117 156 108 168 118 148 113 214 203 160 105 193 137 218 149 186 144 184 144 187 147 189 146 174 132 10 M 116 F . 90 139 109 148 107 164 114 163 121 221 193 201 159 199 134 216 144 191 150 192 151 200 152 199 149 181 136 100 M F 116 89 72 HI 163 98 185 129 231 129 185 190 189 146 198 146 185 145 197 139 189 137 189 146 121 193 187 152 r / T A B L E 111 co ntinued TEST MATERIAU A roclor 1254 Tw o-Year Chronic O ral Toxicity Study - Albino Rata Food Consumption Data Sum m ary of Mean Values Food Consumption Dietary Level of (gram s/rat/aeven days} Average Food A r o c lo r 1254 1i p n l Sex 4 5 6 Mouth: 789 10 II Consumption 12 ( g r a m s / r a t / s e v e n d a v s l Coni rol M 196 189 168 147 163 184 179 170 187 F 148 154 136 121 138 152 160 141 127 176 142 1 M 189 IBI 184 198 190 190 197 152 190 F 141 159 147 162 145 150 151 123 126 186 145 10 M 190 191 189 196 190 188 191 186 163 F 139 138 148 148 150 145 138 142 149 187 144 100 * M 179 168 190 179 187 182 197 180 188 F 148 141 144 162 163 151 148 141 137 183 148 ( I' l* i t- F ybO U M Lr> in C. M o rta lity and Reaction * A frequency distribution of natural deaths occurring during the inve stig a tio n appears in Table IV No untoward behavioral reactions were noted among any of the anim als employed in the investigation. Q Fon09R4 ACM 0C35 OC 362 r n_j o Dietary Level (ppm) Sex Control M F 1M F 10 M F 100 M F .TABLE IV T E S T MATERIAL': A r o d o r 1254 Two-Year Chronic Oral Toxicity Study - Albino Rata Mortality Data Frequency Dlatrlbution of Deathe Frequency Distribution of Deaths Months: 1-3 4-6 7-9 10-12 13-15 16-18 19-21 000 2 17 6 000 1 3 5 7 000 2 5 6 0 200 1 2 15 000 1 3 5 0 0 11 4 2 3 4 00 1 3 2 5 7 10 2 4 4 2 4 22-24 9 3 9 3 10 7 9 6 Total Dead N um ber Tested* 25/35 19/35 30/35 14/35 27/35 22/35 27/35 23/35 Poe a not include the five animale of each sex from every group sacrificed for inter im pathologic studies. o cv o ULTJi_ cn C9E .)() - I0 - 3T 13 D . H em atologic and C lin ic a l Blood C h e m istry Sadies Mean m ale and female hematologic-and clinical blood chem istry d a t a a r e s u m m a r i z e d in T a b l e s V t h r o u g h EC. Values for all param eters investigated w ere within the normal range for the albino rat. No significant differences between test and contra values were observed. AOM C03561 00 , 364 OO o TABLE V T E S T MATERIAL: A ro c lo r 1254 Tw o-Y ear Chronic Oral Toxicity Study - Albino Rata Hematologic Data S u m m ary of Mean Valuea D(Lipeentvamer)ly Sex 3 Total Leukocyte Count (thou aand a/mm^ ) Month: 6 .9 12 18 24 3 Erythrocyte Count (millions / mm^ ) Monti: 6 9 12 1 8 24 Control M 14.0 15.4 1 0 . 1 1 1 . 1 9.9 1 1 . 2 8. 1 8 . 2 8. 7 8 . 8 7. 6 6 . 5 F 9. 1 9.4 6. 7 7.6 8. 8 7.6 7. 5 7.7 7. 3 . 7. a 7. 7 6 . a M 15. 1 15.2 10.9 1 1 . 0 9.8 1 0 . 2 7.5 7.7 8. 1 7. 7 8. 0 8 . 0 100 F 1 1 . 6 1 2 . 2 7.3 8.7 6 . 6 1 1 . 8 7.5 7.6 7.7 6.9 7. 3 6 .4 .ybUl Ul o ou* o o T A B L E VI TE ST MATERIAL: A ro c lo r 1254 Tw o-Y ear Chronic Oral Toxicity Study - Albino Rata Hematologic Data S u m m ary of Mean Valuea Dietary Level Ipnm) Sex Hemoglobin Concentration (g/100 ml) Month: 3 6 9 12 10 24 3 M 17. 1 17. 7 1 5 . 7 1 7 . 6 16. 1 1 3 . 6 51 Control F 1 6 . 9 1 7 . 4 14. 1 16. 7 16. 4 14. 6 50 17H e m a t o c r i t V a l u .) M o n t h: 6 7 12 18 49 48 50 41 47 43 . 46 42 M 1 5 . 6 1 7 . 6 1 3 . 8 1 5 . 6 1 5 . 7 1 5 . 3 47 47 42 44 41 100 F 16. S 17. 8 13.9 14. 5 14.5 1 2 .7 48 47 42 40 37 24 35 38 40 32 \r tfy b u u o i trrffVf Dietary Level (pnml Control TABUE VII TE ST MATERIAL: A ro c lo r 1254 Tw o-Year Chronic Oral Toxicity Study - Albino Rats Hematologic Data Sum m ary of Mean Values Sex 1 M 62.0 F 03.0 Differential Leukocyte Count (Number of Cell p e r Hundred) Lymphocytes Neutrophils Month: Month: 6 9 12 18 24 3 6 __ 9______ 12____ 18 86.6 80.4 78.8 79-0 65.4 16.0 11.4 18.6 20.6 20.0 86 .6 8 6 .8 69.0 70.2 6 1 .4 15.4 11.6 11. 8 . 10.0 29. 2 24 32. 2 36.0 M 8 8 . 2 7 9 . 6 8 5 . 8 8 5 . 2 6 9 . 8 6 8 . 0 10 .8 2 0 . 2 13. 8 14 .2 2 9 . 0 3 0 . 2 100 F 92.2 92.0 79.6 84.6 79.0 61.0 7.4 7.8 20.2 15.0 20.4 37.6 ! i < II 1 i I ! I >_ O I O TABLE Vii continued TEST MATERIALI A ro clo r 1254 Two-Year Chronic Oral Toxicity Study - Albino Rata Hematologic Data Sum m ary of Mean Values Dietary Level (npm) Control Sex 3 M 0.6 a F 0.6 Differential Leukocyte Count (Number of Celia p e r Hundred) Monocytea Eoilnophlla Month: Month: 6 9 12 18 24 3 6 9 12 18 0.0 0.0 0.4 0.2 1.2 1.4 2.0 1.0 0. 2 0. 8 0.0 0.0 0.0 0.2 1.0 1.0 1.8 1.4 0. 2 0. 6 24 1.6 1.6 M 0.0 0.0 0.0 0.0 0.0 0.8 1.0 0.2 0.4 0.6 1.2 1.0 100 F 0.0 0 .0 0.0 0.0 0. 1.0 0.4 0.2 0.2 0.4 0.6 0 .4 O S b U U .l Ul O CD o I- r {\ \ y oo o Dietary Level (ppm) Control Sex M i F M 100 F T A B L E VII continued TEST MATERIAL: A roclor 1254 . Two-Year Chronic Ora! Toxicity Study - Albino Rata Hematologic Data Sum m ary of Mean Valuea f Differential Leukocyte Count (Number of Cella per Hundred) Basophils Month: 3 6 9 12 IA 24 0.0 0.0 0.0 0.0 0.0 0.0 0.0 0.0 0.0 0.0 0.0 0.0 0.0 0.0 0.0 0.0 0.0 0.0 0.0 0.0 0.0 0.0 0.0 0.0 rV 1 l i TbU U O j ocr * in r~ } ( \ ry k o T A B L E VIII T E S T MATERIAL: A ro clo r 1254 Two-Year Chronic Oral Toxicity Study - Albino Rata Hematologic Data Summary of Mean Valuea Serum Glutamic-Pyruvic Blood Urea Nitrogen Tranaamlnaee-Actlvity Concent ration Dietary (Dado Units) ( m g s %) Level Month: Month: (ppm) Sex 3 6 9 12 18 24 3 6 9 12 18 M 38 48 45 45 42 36 17 15 12 10 14 Cont rol F 33 39 38 42 32 30 14 16 15 9 13 M 33 32 43 *50 38 41 14 15 13 12 11 100 F 32 46 49 61 46 78 16 15 13 14 13 24 15 11 15 15 n u \ i ^tftUUUtf . un------- -----------------------------------------------------------------------------------------O r _________________________________ ____ _________________________________ 4 -o o. O oo TABLE IX TEST MATERIAL: A ro clo r 1254 Tw o-Y ear Chronic O ral Toxicity Study - Albino Rata Hematologic Data Dietary Level Sex 1 Summary of Mean Valuea F a a t e d Blood GIucobo Concentration (m ga %) Mouth: 6 9 12 18 24 3 Scrum Alkalino Phoaphataae Activity (Klng-Armatrong Unita) Month: 6 9 12 18 24 Control M F 128 123 89 130 118 115 88 138 99 28.6 24.7 21.5 20. 3 16.2 22. 3 92 134 109 18.9 1 7 . 8 10.6 11.9 16 . a 2 0 . 2 * Vi 100 M 109 113 129 128 124 115 3 5 . 4 2 3 . 2 2 7 . 4 27. 1 1 4 . 6 2 3 . 5 r- fi F 120 107 124 113 132 107 17. 1 18. | 19 .3 16 .7 1 0 .0 2 1 . 6 I V; A C M 003565 IuV B I O - r e S 7 A+ M aJauM , 5* 6 E. Urine Analyses M ean m ale and fem ale urine analyses data are summarized in Table X through X II. No differences w ere noted between the u rin e fro m control and test animals at the intervals of examination. oo 4 TABLE X TEST MATERIAL: A roclor 1254 Two-Year Chronic Oral Toxicity Study - Albino Rata Urine Analyses Data Summary of Mean Values Dietary Glucose Albumin Level Month: Month: (ppm) Sex 3 6 9 12 18 24 3 6 9 12 18 24 Control M F nn n 'n n n n n nn n t n `n n n n n t 2 43 nt 42 r M n n n n n n n n t t t 42 100 s Fn n n n n nn n t t t 43 O Ui Ui o IP IT *5 5 Key: .... ? n = negative ^ * - tra c e ; l e s s than 30 m g /1 0 0 m l u r in e 4 I = 30 to 100 m g / 1 0 0 m l u r i n e 42 = 100 to 300 m g / 1 0 0 m l u r i n e 4 3 = 300 to 500 m g / 100 m l u r i n e * '1 = m o r e than 500 n i g / 100 m l u r i n e BIO. ir Ui r. f r s T A B L E XI TEST MATERIAL: A roclor 1254 Two-Year Chronic Oral Toxicity Study - Albino Rats Urine Analyses Data Sum m ary of Mean Values Dietary Microscopic Elements pi I Lo voi Month: Month: P* I 5 . x 1 6 9 12 18 24 3 6 9 12 IS 24 r*iii| :% n n n n ll 7 7 6 7 7 6 r r. I r * n n nt t887 86 6 % i* n %n nt t776 76 6 p ss n n N t t 8 8 7 7 6 6 o >. V-J 5 O o -W. Key; K - X. trina I n a nii^ativs t trace; less than 5 per low power field + I a 5 to 10 p e r low p o w o r field 2 = 10 to 15 p e r low p ow e r field 11 = m o r e Ilian 15 p e r low p o w e r field o> O m 6M0 Dietary Level (npml Control Sex M F M 100 F r' V. o TA B L E XII TEST MATERIAL; A roclor 1254 Two*Year Chronic O ral Toxicity Study - Albino Rata Urine Analyses Data 3 1.029 1.020 Summary of Mean Values Specific Gravity Month; 6 9 12 1.022 1.033 1.027 1.019 1.025 1.024 IB 1.042 1.032 1.018 1.020 1.021 1.018 1.029 1.023 1.027 1.022 1.037 1.029 / iv o 24 1.051 1.039 1.027 1.031 03 O r.i i/i U hI- bJj U U U jl vrl rA ? /l f ( MIS# I * Pathologie Studios J, T h ree Month Sacrifice a. Gross Pathologie Findings No outstanding differences w e re noted between test and control rats upon gross pathological examination. b. O r g a n U'elg ht and O rg a n to Bodv and O r g a n to B r a i n V.'cigiit Ratio Data .* Th e r e s u l t s of the s t a t i s t i c a l a n a l y s e s co nducted on absolute organ weights, organ to body weight and organ to brain weight r a t i o s a r e s u m m a r iz e d in Tables XIII thro u g h XVIII. Significant differences between a test group and the control group are designated by asterisks following the test value. Organ weights, organ to body weight and organ to b rain weight ratios disclosed several randomly occurring intergroup differences. The laek of any consistent dose related response and the absence of any deleterious histopathologie change confirm that these differences were not related to the ingestion of Aroclor 54. O K- w F ,nnfW 98 AQ* 0 0 3 5 7 3 OC 376 Dietary Level of A roclor 1251 fppml Control 1 10 100 TE ST MATERIAL: A ro c lo r 1254 Tw o-Year Chronic Oral Toxicity Study - Albino Rata Organ Weight and Ratio Data Three-Month Sacrifice Summ ary of Mean Values Organ: Liver Organ Weight (g) Malea Female 21.4 13.0 24.0 13.5 22.8 13.1 28.0* 13.8 Organ/Body Weight Ratio (g /1 0 0 g) M a l e a ______ F c m a l e a 4.13 4.16 4.34 4.34 4.59 5.25 4.29 4.89 O rgan/D rain Weight Ratio (g/g) M a l e a _______F e m a l e s 10.3 11.7 10.9 14.6** 6.82 6.85 6.85 7.11 OWUUi Statistically significant difference at the 95 percent confidence level. ** S t a t i s t i c a l l y s ig n i f i c a n t d i f f e r e n c e at the 99 p e r c e n t c o n f i d e n c e l e v e l . o o _LJ - - n . c v O O O i U i Dietary Level of A ro c lo r 1254 fpnml Control 1 10 100 O ** u> -J o CO o IP -- -- -a - TABLE XIV TEST MATERIAL: A ro c lo r 1254 Two-Year Chronic Oral Toxicity Study - Albino Rato Organ Weight and Ratio Data Thrce'iVlonth Sacrifice Summary of Mean Valuea Organ:. Kldneya Organ Weight (el Males F em ales 4.03 2.49 4.30 2.62 4.05 4.21 2.61 2.74 Organ/Body Weight Ratio ( g / 1 0 0 g) Malea Females 0.7B2 0.802 0.77B 0.B45 . 0.B21 0.792 0.852 0.975 O rgan/Braln Weight Ratio (t'/fi) Males F em ales .1.95 2.09 1.94 2.19 1.31 1.32 1.36 1.42 SI0 -T E5T I'i ( \\ o Dietary Level of A ro c lo r 1254 (pnm) Control 1 10 100 rrj C7 o J.V` t> ' '> , TA B L E XV T E S T MATERIAL: A r o c lo r 1254 Tw o-Year Chronic Oral Toxicity Study - Albino Rats Organ Weight and Ratio Data Three-Month Sacrifice Sum m ary of Mean Values Organ: Spleen o Organ Weight Males m (g) Females 0.766 0.57B 0.942 0.668 0.766 0.586 0.814 0.542 Organ/Body Weight Ratio ( c / ) 0 0 &) Males Females 0.150 0.184 0. 167 0.217 0.154 0.153 0. 191 0.192 O rgan/B rain Weight Ratio (g/g) Males Female 0.371 0.454 0.368 0.425 0. 302 0. 338 0.308 0.281 AOa CO35 7 6 r .Dietary Level of A ro c lo r 1254 (ppm) Control 1 10 100 T A B L E XVI TE ST MATERIAL: A ro c lo r 1254 Tw o-Y ear Chronic Oral Toxicity Study - Albino Rate Organ Weight and Ratio Data Three-Month Sacrifice Sum m ary of Mean Values Organ: Gonads Organ Weight (g) Males Fem ales 3.60 0.114 3.50 0.134 3.55 0.110 3.82 0.120 Organ/Body Weight Ratio ( g /1 0 0 g) Males Fcmates 0.698 0.0370 0.637 0.0431 0.720 0.0361 0.718 0.0426 O rgan/B raln Weight Ratio fg/g) Males F em ales 1.74 1.70 0.0599 0.0675 1.70* 0.0568 1.99 0.0618 08E 0 0 - wor 381 V jr t O Dietary Level of A ro c lo r 1254 (ppm) Control 1 10 100 p p 5 W T A B LE XVII T E S T M A T ER IA L : A r o c l o r 1Z54 Two-Year Chronic Oral Toxicity Study - Albino Rata Organ Weight and Ratio Data Three-Month Sacrifice Summary of Mean Values Organ: Heart Organ Weight (si Male Females * 1.59 1.05 1.56 1.02 ' 1.49 0.984 1.58 0.992 Organ/Body Weight Ratio (g/ioo g) Males Females 0.307 0.339 0.283 0.332 0.302 0.322 0.297 0.352 O rgan/B ratn Weight Ratio (e/c) Males F em ales 0.767 0.551 0.756 0.516 0.713 0.515 0.817 0.512 \ P r fP \J O Dietary Level of A r o c lo r 1254 (ppm) Control 1 1 100 - *5--------------------------- X 0L0J KJ OOo f b uV** ^ 4) TABLE XVIII TE ST MATERIAL: A ro c lo r 1254 Two-Year Chronic Oral Toxicity Study - Albino Rate Organ Weight and Ratio Data Three-Month Sacrifice Sum m ary of Mean Values Organ: Drain Organ Weight (g) Malea Females 2.07 1.91 Orgavi/Body Weight Ratio (C/I00g) Malea Females 0.402 0.616 Final Body Weights f Sacrificed Rata (fi) Males F em ales 518 314 2.07 1.99 0.376 0.647 553 311 2.09 1.91 0.424 0.625 499* 307 1.95 1.94 0.366 0.688 434 281 n\ ' L ' 5E'5-r -S. j: e H i s t o n a t h o t o g i c F in d i n g s Histopathologic examination of tissues and organs t a k e n f r o m a l l a n i m a l s f r o m both the c o n tr o l and 100 pp m g r o u p s w as conducted. T a b l e s XIX and XX li s t all his to p a th o lo g ic changes noted. All of the lesions noted in the m i c r o s c o p i ^ e x a m i n a tion of t i s s u e s w ere those of spontaneous d isease and a re not unusual for the albino rat. The m ost frequent findings w ere lesions in the trachea and lungs, indicating chronic murine pneumonia. These oc c u rre d in the control as well as the rats fed A roclor 1254. r AOP 0G358C 383 00 o TABLE XIX T E S T M ATER IA L: A r o c lo r 1254 Tw o-Y ear Chronic O ral Toxicity Study - Albino Rata Histopathologic Changes Three-Month Sacrifice Croup; Control Num ber of Animals Orean Examined Findings S Males * Trachea Lung Urinary Bladder Tracheitis Chronic respiratory disease Hyperplasia 5 Fem ales Lung Chronic respiratory disease Aver lneider.ee C ra l l.C 1 ' l.C 3 l.C 1 1.0 All other tissues and organs were normal histologically. Grading System 0.5 a minimal 1.0 * slight 2.0 = mild 3 .0 = moderate 4.0 a severe 5.0 * extreme ADM 0035 0 ( 384 T A B L E XX T E S T M ATERIAL; A ro c lo r 1254 Tw o-Y ear Chronic Oral Toxicity Study - Albino Rata Histopathologic Changes Three-Month Sacrifice C ro u p : 100 pp m N u m b er of Ave rag A n i m a l s ---- O r g a n E x a m i n e d - ---------- F i n d i n g s ------- . In c id e n c e .. . . C ra d e 5 Males Trachea Lung Tracheitis 1 1.0 Chronic respiratory disease 3 1.0 5 Females Trachea Tracheitis 1 1.0 All other tissues and organs were normal histologically. ( Grading System 0 .5 = minimal 1.0 = slight 2.0 = mild 3.0 s moderate i 4. 0 = seve re 5.0 s extreme i!. J',001007 ACM 00 35 d OC 385 0 l V. 1 C 3 1 2. 5ixM orth -gi c r i f i c g a. Cross Pathologie Findings No outstanding differences were noted between test and control animalj. f b. Crcan h e ig h t and Qr?an to Bodv and O rg a n to B rain V.'eirht Ratio Data The results of the statistical analyses conducted on absolute' organ weights, organ to'body weight and organ to brain weight"" r a tio s a r e su m m a riz e d in Tables XXI through XXVI. Organ weights, organ to body weight and organ to b ra in 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 w ere l not re la te d to the ingestion of A ro c lo r 1254, AO* CCJ5a oc 386 /A o TA BLE XXII 9 TE ST MATERIAL: A ro c lo r 1254 Two-Year Chronic Oral Toxicity Study - Albino Rata Organ Weight and Ratio Data ` Six-Month Sacrifice Summary of Mean Values Organ: Kidneys Dietary Level of A r o c l o r 125-1 (ppm) Cont rol 1 10 100 Organ Weight (g) Males Females 4.04 2.79 3.80 2.58 3.22** 2.50 3 . 2 3 1* 2.43 Organ/Dody Weight Ratio (g /1 0 0 g) Males Females 0.664 0.806 0.715 0.7B4 0.703 0.760 0.700 0.861 Organ/D raln Weight Ratio (g/g) Males F em ales 2.06 1.43 1.75* 1.39 1.57+ . 1.31 1.68* 1.25 o i * Statistically significant difference at the 95 percent confidence level. C0 *7bs edo wov gSE 00 rr' TAflLE XXI TE ST MATERIAL: A ro c lo r 1254 Tw o-Year Chronic Oral Toxicity Study - Albino Rata Organ Weight and Ratio Data Six-Month Sacrifice Summary of Mean Values Organ: Liver- Dietary Level of A roclor 1254 (on:u| Organ Weight <c> Malea Female# Organ/Body Weight Ratio ( g / 1 0 0 g) Malea Fem ales O rgan/B raln Weight Ratio Ce/cl Malea F em ales Control 22.9 13.1 3.74 3.77 11.7 6.71 1 16.1** 10.3* . 3.0f*> 3 . n * `* 7.45** 5.54* 10 I2.9** 9.54* 2.81** 2.94** 6.29** 4 .9 9 ' 100 19.2 12.4 4.14 4.40 > S t a t i s t i c a l l y s ig nif ic a nt d i f f e r e n c e a t the 95 p e r c e n t c o n fi d e n c e l e v e l , O Statistically significant difference at the 99 percent confidence level. 10.0 ----- 1------------------- 6.39 t i ( ii/t I. i; i t. ) o D.t'.ary Level of A ro c lo r 1254 {->pml Cunt rot 1 10 *100 oo T A B ^ E XXIII TE ST MATERIAL: A ro c lo r 1254 Tw o-Y ear Chronic Oral Toxicity Study - Albino Rate Organ Weight and Ratio Data Six-Month Sacrifice Summ ary of Mean Values Organ; Spleen Organ Weight (g) Males Fem ales 0.752 0.684 0.830 0.602 0.588 - 0.594 0.684 0.512 Organ/Dody Weight Ratio (g /1 0 0 g) Males Fem ales 0.122 0.196 6.155 0.182 0.128 0.184 0.150 0.180 O rgan/B raln Weight Ratio i f * / } Males F em ales 0. 384 0. 350 0.384 0.324 0.287 0.311 0.356 0.264 ACM o o U Ul <x> BStOO U0v r ) o Dietary Level of A ro c lo r 1254 (omnl Coni rol 1 10 100 oo T A B I.E XXIV TE ST M ATERIAL: A ro c lo r 1254 Tw o-Year Chronic Oral Toxicity Study - Albino Rata Organ Weight and Ratio Data Six-Month Sacrifice Summary of Mean Values Organ: Gonads a Organ Weight (g) Males Fem ales 3.55 0,0960 3.6? 0.0922 3.30 O.OB68 3.44 0.104 Organ/Body Weight Ratio ( g / 1 0 0 g) Males F em ales 0.593 0.691 0.0279 0.0280 0.724 0.0272 0.747 0.0364 O rgan/B raln Weight Ratio (g/gl Males Fem ales 1.81 1.70 0.0492 0.0496 1.61 0.0454 1.79 0.0536 -) o Dietary Level of -A roclor 1254 fpnin) Control 1 10 100 o oo TABLE XXV TEST MATERIAL: A ro c lo r 1254 Tw o-Year Chronic Oral Toxicity Study - Albino Rata Organ Weight and Ratio Data Six-Month Sacrifice Summary of Mean Values Organ: Heart Organ Weight (8> Males Fem ales 1.70 1.05 1.58 1.44 1.04 1.03 1.40 1.02 Organ/Body Weight Ratio ( g /1 0 0 g) Males Females 0.282 0.302 0.298 0.316 0.314 0.320 0.301 0.361 O rgan/B ratn Weight Ratio Males F em ales 0.667 0.538 0.731 0.702 0.559 0.539 0.729 0.526 ACM CC3 ` 2 3 r> j O Dietary Level of A ro c lo r 1254 (pnntl Control 1 10 100 TA BLE XXVI *I TE ST MATERIAL.! A r o c lo r 1254 Two-Year Chronic Oral Toxicity Study - Albino Rats Organ Weight and Ratio Data Slx-Monlh Sacrifice Summary of Mean Values Organ; Drain - Organ Weight (fi> Males Females 1.96 . 2.16 1.86 2.05 1.91 1.92 1.94 Organ/Body Weight Ratio ( g / 1 0 0 g) Males F em ales 0.320 0.560 0.404 4 0.562 0.447*'* 0.593 0.414** 0.681** Final Dody Weights of Sacrificed Rats Males ( t: ) F em ales 613 348 534 331 459 322 464 285 ^ * Statistically significant difference at the 95 percent confidence level. O Statistically significant difference at the 99 percent confidence level. -- .> 392 e. H istopathologic T i ndi.-.gs H i s t o p a t h o l o g i c e x a m i n a t i o n o t i s s u e s and o r g a n s ta k e n f r o m a l l a n im a ls f r o m bath the co n tro l and 100 p p m groups was conducted. T ables XXVII and XXVIII list all histopathologic changes noted. All of the lesions noted in the m icro sco p ic examination of tis su e s w e re those of spontaneous disease and a r e not unusual for the albino rat. The m ost frequent findings w ere lesions in the trachea and lungs indicating chronic murine pneumonia. These occurred in the control as w ell as the rats fed A roelor 1254. AC* 00 1 * ? C F .0 ( V W * * ^ 393 j , TAB LS XXVII T E S T M A T E R IA L : A ro c lo r 1254 T w o -Y e a r Chronic O ral Toxicity Study - Albino Rats Histopathologic Changes Six-Month Sacrifice Group: Control N um ber o Anim als 5 Males O r can Examined Findings Trachea Lung L ive r S keletal Muscle ^ Tracheitis Focal tracheitis Focal pneumonitis Hyperem ia Focal pericholangitis Fo cal infiam m atio n Incidence 22 1 2 *1 1 A ve ra G radi 11 ..50 * 0.5 1.0 1.0 1.0 5 Fem ales Trachea Lung L ive r K id n e y Focal tracheitis H yp e re m ia Hyperem ia P e ric h o la n g itis Focal inflam m ation 21 * 1.0 2 .5 1 1.0. 1 1 0.5 1.0 A ll other tissues and organs were norm al h isto log ica lly. Grading System 0.5 * m inim al 1.0 a slight 2 . 0 * m ild 3.0 * moderate 4.0 severe 5.0 * extrem e % o o ^ ' 91 JkC" 394 0. c L 1 t a b l e x x v iii Q T E S T M A T E R I A L : A r o c l o r 125-t T w o-Y ear Chronic Oral Toxicity Study - Albuio Rats Histopathologic Changes Six-Month Sacrifice G r o u p : 100 p p m Number of Animals 5 Males 5 Females O m r . Examined Trachea Lung Liver Kidney Heart Trachea Lung Kidney Findings Tracheitis Focal tracheitis Focal pneumonitis Focal pericholangitis Focal nephritis Myocarditis Focal tracheitis Focal pneumonitis Hyperemia * Focal nephritis Incidence 2 1 3 1 l 1 3 4 X 2 Ave rag G rade 2.0 1.0 0.5 2.0 0.5 0 5 0.5 1.0 1.0 3.0 ' All other tissues, and organs were normal histologically. Gfading System 0.5 9 minimal 1.0 * slight 2.0 * mild 3.0 = moderate 4.0 s severe 5.0 extreme L- ' AOH 0 0 3 5 9 2 Of 395 3. Twclyc-M onth S acrifce a. ' Cross Pathologie Findings Gros pathologic findings among test animals were not s i g n i f i c a n t l y d i f f e r e n t f r o m th os e noted Ln c o n t r o l a n i m a l s . b. Organ Weight and Ratio Data The mean organ weight and ratio data collected at the 12- m o n t h s a c r i f i c e a r e p r e s e n t e d in T a b l e s XXDC t h r o u g h XXXIV. Statistically significant differences* a re designated by asterisks following the test group value. Organ weights, organ to body weight and organ to b ra in weight ratios disclosed several randomly occurring intergroup differences. The lack of any consistent dose related response and the absence of any deleterious histopathologic ehange confirm that these differences were not re la ted to the ingestion of Aroclor 1254. *0* / r TABLE XXIX TEST MATERIAL.: A rocior 1254 Tw o-Y ear Chronic Oral Toxicity Study - Albino Rat* Dietary Level (anm) Control 1 10 100 Twelve-Month Sacrifice Organ Weight and Ratio Data Sum m ary of Mean Valuea Organ Weight (g) Males Females Organ: Liver Organ/Body Weight Ratio (g /1 0 0 g) , Mates Females . 22.1 20.6 23.5 27.1* 12.9 14.6 12.2 3.79 3.09* 3.52 4.58* i 3.52 3.41 4.34 3.43 O rgan/B raln Weight Ratio (g/g| Males Fem ales 10.8 7. 72 9.89 7. 29 11.2 7.34 12.7 6 . 30 * Statistically significant difference at the 95 p e rc en t confidence level. ij VO VI 1001019 o sJ o Dietary Level loom) Control 1 10 100 T A B L E XXX T E S T M A T E R I A L : A r o c l o r 125-4 Tw o-Y ear Chronic O ral Toxicity Study - Albino Rata Twelve-Month Sacrifice Organ Weight and Ratio Data 9 % Summary of Mean Values Organ: Kidneys Org an Weight Males (g> Females Organ/Doily Weight Ratio (g /1 0 0 g) Males Females O rgan/B raln Weight Ratio Males Fem ales 4.04 4.09 4.64 4.39 3.19 2. 75 2.76* 2.78* 0.692 0.618 0.697 0.740 0.738 0.728 0.817 0. 796 1.97 i. 98 2.21 2. 06 1.58 1.55 1.39 1. 44 1 .0 0 1 0 2 0 00 * S tatistically significant difference at the 95 p e rc e n t confidence level. i CJ V0O0 ) r `t s n r j - r r r - I C T l | fl Dietary Level fanm) Control 1 10 100 TA BLE XXXI TE ST M ATERIAL: A ro c lo r 1254 Tw o-Y ear Chronic O ral Toxicity Study - Albino Rata Twelve-Month Sacrifice Organ Weight and Ratio Data Sum m ary of Mean Valuea Organ: Spleen Organ Weight Males (g) Fem ales Organ/Body Weight Ratio (g/100 g) Males Females O rgan/B raln Weight Ratio (g/g) Males F em ales 0.778 0.714 0.904 0.754 0.796 0.484* 0. 548 0.976 0. 133 0. 107 0. 135 0.126 0.183 0. 129 0.161 0.280 0. 380 0.344 0.430 0.352 0. 396 0. 271 0.275 0.517 * S tatistically significant difference at the 95 p e rc en t confidence level' u> ID 10 w> Min f\ r Dietary Level (mm) Control 1 10 100 TABLE XXXII TE ST MATERIAL: A ro clo r 1254 Tw o-Y ear Chronic O ral Toxicity Study - Albino Rats Twelve-Month Sacrifice Organ Weight and Ratio Data S um m ary of Mean Values Organ: Gonads Organ Weight (g) Males Females Organ/Body Weight Ratio (g/100 g) Males Females ' 3.46 3.68 3.68 3. 56. 0.116 0. I ll 0.0918 0.121 0. 592 0.557 0.550 0.603 0.0275 0.0294 0.0270 0.0334 r O rgan/B raln Weight Ratio (g/g) Males F cmales 1.70 0.0574 1.78 0.0624 1.75 0.0461 1.67 0.0624 o .u z o oo oU) ill n o Dietary Level (onml Control 1 1 to 1 too TA BLE XXXIII TEST MATERIAL: A ro c lo r 1254 Tw o-Y ear Chronic O ral Toxicity Study - Albino Rate Twelve-Month Sacrifice O rgan Weight and Ratio Data. Sum m ary of Mean Values Organ: Heart Organ Weight (e) Males Females Organ/Body Weight Ratio (ii/100 g) Males Females 1.71 1.68 1.84 1.25 i.n l . 08** 0.293 0.255 0. 275 0. 286 0.301 0.322 1.69 1. 14 0. 284 0. 325 O rgan/B ratn Weight Ratio <b / b ) Males Fem ales 0.835 0.609 0.812 0.635 0.875 0.544* 0.795 0.589 o CD u >oT o O o S ta tistic a lly significant difference at the 95 p e r c e n t confidence level. > S t a t i s t i c a l l y s i g n i f i c a n t d i f f e r e n c e at the 99 p e r c e n t c o n f i d e n c e level. rO Dietary Levol (pom) Control 1 3 10 -A 100 TABLE XXXIV TE ST MATERIAL: A ro clo r 1254 Two-Year Chronic Oral Toxicity Study - Albino Rata Twolve-Month Sacrifice O r g a n W e ig h t a nd Ratio* Data Summary of Mean Values Organ Weight (s) Males Females 2.04 2.02 2.08 . 1.78 2. 10 1.99 2. 14 1.93 Organ: Brain Organ/Body Weight Ratio ( c / i o o g) Males Female 0.35 0.474 0.315 0.475 0. 315 0.591 0.361 0.552 Final Body Weight of Sacrificed Anlmala (gran Males Fcma lea 5B4 439 665 380 669 338; 596 355 'U U ) U i * Statistically significant difference at the 9$ p e rc e n t confidence level. ou w o o i c Histopathologie Findings Histopathologic examination of tissues taken from each ra s a c r i f i c e d f r o m th e c o n t r o l and 1Q0 p p m g r o u p s a f t e r 12 mo nt hs of t e s t i n g was conducted. Tables XXXV and XXXVI list all histopathologic changes noted. V. F001025 a c* 0C3cCC 403 0 jiU + d * * 1 w 6 5 1 TABLE XXXV TEST M A TER IA L: A ro c lo r 1254 T w o -Y e a r Chronic O ral Tosdcity Study - Albino Rats Histopathologic Changes Twelve-M onth Sacrifice Group: Control Number oi Anim als 5 M iles 5 Fem ales Organ Examined Trachea Lung U rin a ry Bladder Trachea Lung Colon Findings T ra c h e itis Chronic resp iratory disease Calculus T ra c h e itis Cdhirsoenaiscere s p ira to ry P a ra s ite s Incidence 1 2 1 1 1 1 A ll other tissues and organs were norm al h is to lo g ic a lly . Grading System 0.5= m inim al 1.0 = slight 2.0 = m ild 3.0 a moderate 4.0 * severe 5.0 * extreme Ave C `r 1 11 , i, . 1. 1i1 . 1. 1. ! 1001 O yS A C M 0C36C1 0 ( 404 ' f l f B i C " S 5 T J zS a v i Y u tj. 2* S'# T A B L E XXXVX TEST MATERIAL: A ro clo r 1254 T w o -Y e a r Chronic Oral Toaricity Study - Albino Rats Histopathologic Changes Twelve-Month Sacrifice Group: 100 p p m N um ber of O rgan Animals Examined Findines Aver a ....... * I n c id e n c e ~ " G ra c 5 Males Lung Chronic respiratory disease 4 uo 5 Females Heart Trachea Lung Adrenal Focal myocarditis Tracheitis Chronic respiratory disease Congestion 1 1.0 1 1 . `0 1 1.0 1 : 1.0 Q s*1^ ' A l l o t h e r t i s s u e s a n d o r g a n s w e r e n o r m a l h i s t o l o g i c a l l y . G' r a d i r . ?" S v' s t e m 0.5 s minimal 1 0 s s l i g h t 2.0 = mild 3. 0 = m oderate 4. 0 s severe 5. 0 a extrem e . K not 0^7 ADh 0 036C i 00 405 4. Final Sacrifice Gross Pathologic Findings G ro s s pathologic findings among te st animals were not significantly different from those noted in control anim als, b. Organ V'eight and Ratio Data The m ean organ weight and ratio data collected at the f i n a l s a c r i f i c e a r e ' p r e s e n t e d in T a b l e s XXTCVH t h r o u g h X L II. Statistically significant d ifferen c es, a r e designated by a s te ris k s following the test group value. Absolute liver weight, liver to body weight and liv e r to b ra in weight ratios were significantly elevated in both male and female r a t s fed 100 p p m A r o c l o r 1254. O th e r organ w e ig h ts , o r g a n to body w e i g h t and o r g a n to b r a i n wei ght r a t i o s d i s c l o s 'ed s e v e r a l r a n d o m l y o c cu rring intergroup differences. The lack of any consistent dose related r e s p o n s e and the absence of any deleterious histopathologic change confirm th a t these d ifferen ces w ere not related to the ingestion of A roclor 1254. F .n m o ? 8 ACM i i 0C3t0 0 0 0 406 i o O' - Dietary Level <PPn! Control 1 10 100 TABLE XXXVII T E S T M ATERIAL: A ro c lo r 1254 Two-Year Chronic Oral Toxicity Study - Albino Rato Organ Weight and Ratio Data t Summ ary of Mean Values Final Sacrifice Organ Weight Males (el Females Organ: Liver O r g a n / 11oily W e ig h t R a t i o (6/ >0 0 E) Malen Females 22.0 16.3 3.47 3.05 19.5 23.9 30.2** 16. 1 19.5 32. 2.99 3.21 4.75** 3. 10 3.84* 8.62** a S tatistically significant difference at the 9S p e rc e n t confidence level. * ** Statistically significant difference at the 99 p e rc e n t confidence level. O rgan/B rain Weight Ratio (ti/cl Males Females 10. 10 8.42 8.76* 8.31 11.40* 10. 30 1 4 .10* 17. 10* AUH 003604 Fomo?9 ooo 407 O . Dietary Level (ppm) Control 1 10 100 TABLE XXXVIII T E S T M A T E R IA L : A ro c lo r 1254 Tw o-Y ear Chronic Ora! Toxicity Study - Albino Rata Organ Weight and Ratio Data Summ ary of Mean Values * Final Sacrifice _ _ _ _* Organ Weight (g) Males Females Organ: Kidneys Organ/lJody Weight Ratio (g/100 g) Males Females 5. 57 5.52 5.61 5.48 3.68 3.47 0.877 0. 868 0.761 0.646 0.706 0.717 4.74 3.44 0.749 0.899* Statistically significant difference at the 95 percent confidence level. o ! a 1 | , 1 | j a O rgan/B rain Weight Ratio j (g/g) Males Femates 2.57 2.48 2.70 2.21 1.79 1.88 1.84 1.82 Ffl01030 0 0 0 408 1a. Dietary Level (ppm) Control ^1 O io > too TABLE XXXIX TEST MATERIAL: A roclor 1254 Two-Year Chronic Oral Toxicity Study - Albino Rata Organ Weight and Ratio Data Sum m ary of Mean Values Final Sacrifice . Organ Weight Males <cl Females 1. 15 0.96 1.26 1.06 1.57 0.86 1.04 0.66 Organ: Spleen Organ /Body Weight Ratio ( g / 100 g) Males Females 0. 182 0. 181 0. 189 0.237 0.220 0. 164 * 0. 175 0 . 174 J j ( * J f l i; O rgan/B raln Weight Ratio Ma lea Female a 0.520 0.492 0.568 0.562 0.749 . 0.462 0.489 0.352 O CD O o o KO ooUOf tl' o ; o * Dietary Level . (ppm) Control 1 10 100 . TABLE XL T E S T M ATERIAL: A ro c lo r 1254 Two-Year Chronic Oral Toxicity Study - Albino Rata Organ Weight and Ratio Data i Summary oi Mean Valuea Final Sacrifice Organ Weight fg) Males Females 2.52 0. 123 Organ: Gonads Organ/B*dy Weight Ratio (g/100 g) Males Females 0.397 0.0222 3. 19 0.204 0. 482 0.0390 3.28 0.135 0 . 4 15 0.0283 3.44 0. 128 0.547 0.0316 o c n if ii t V * V, O r^an/B rain Weight Ratio ^ (g/g) Males Females 1. 15 0.0626 1.43 0. 1010 1.56 0.0707 1.60 0.0666 * Statistically significant difference at the 95 p ercen t confidence level O ADM 0 0 3 6 0 7 O Ac Enmn.32 Dietary Level (pomi Control 1 10 2^100 TABLE XLI T E S T M A T E R IA L I A ro c lo r 1254 Tw o-Year Chronic Oral Toxicity Study - Albino Rate Organ Weight and Ratio Data I S u m m a r y oC M e a n V a l u e s Organ Weight Males <C> Females 1.87 1.54 1.98 1.55 2.08 1.37 1.94 1.50 Final Sacrifice Organ: Heart Organ/11 udy Weight Ratio (g/100 g) Matos Females 0.294 0.288 0.301 0.302 0.279 0.282 0.304 0.386* * Statistically significant difference at the 95 percent confidence level. ^ S tatistically significant difference at the 99 percent confidence level. O O AP- 0 0 3 6 0 8 i: I. . i i -ai ii ut -- I F O rgan/B rain Weight Ratio (&/g) Malos Females 0. 860 0.795 0. 889 0.805 0.998* 0.727 0.909 0. 803 uOn' - V * v -------' 000 T'C Dietary Level Ippm) Control 1 10 100 o TABLE XLII T E S T M ATERIAL: A ro c lo r 1254 Two-Year Chronic Oral Toxicity Study - Albino Rate Organ Weight and Ratio Data i Summ ary of Mean Values , Organ Weight . (e) Males \ Females Final Sacrifice Organ: llraln Organ/Body Weight Ratio ( c / l g> Males Female Final Body Weight of Sacrificed Animals (grams) Ma les Fcma les CO s 2.22 2. OB . 2. 13 1.95 1.94 I.8B I.B8 0. 342 0. 347 0. 279 0. 340 0. 362 0.376 0. 388 0.486** 642 55 1 656 540 762 500 656 4 1to* A I 0 --J 1 in !> ji ** S tatistically significant difference at the 99 p e rc e n t confidence level. J ADM 003609 O' O' " n d u i i* 1^ D I `F t i i 67 c. His^tooatho logic Findings Histopathologic examination of tissues and organs f r o m all a n im a ls s a c r if ic e d a f t e r 24 m onths on t e s t was conducted* Ta ble s XX.HI t h r o u g h XLVI l i s t all Histcoathol'ogic c han note d. T a b le X1.VII contains the r e s u l t s of the histopathologic e xam inatic of the urinary bladders. Significant liver injury was found in anim als fed 100 ppr A r o c l o r 1254 ( T - HI). The co mp oun d a s s o c i a t e d l e s i o n s c o n s i s t e d of vacuolar change, focal hypertrophy and focal hyperplasia. la addition, there w ere lesions of inflammation, necrosis, fibrosis and m in o r d e generation, w ere more severe and frequent in the T-HI group.. The vacuolar change was not seen in the control anim als b u t w a s o b s e r v e d o c c a s io n a ll y in l i v e r s f r o m T - I (1 ppm) and T-XI (10 pprr a n i m a l s . Xt w a s fr e q u e n t in the T - I I I a n i m a l s . T h i s l e s i o n is m o r p h o l o g ic indicative of fatty degeneration. Form alin-frozen sections of livers from r e p r e s e n t a t i v e a n i m a l s which d i s p la y e d v a c u o l a r ch an g e s w e r e s t a i n e d wit] Oil Red 0 to reveal the presence of fat. The vacuolar lesion in the cytopla of th e s e c e l l s w as positively idenified as fat. '- The h y p e rtro p h ic changes found in the liv e r was fo c a l anc often l i m i t e d to the c e n t r a l l o b u l a r a r e a w h e r e g r o u p s of c e l l s w e r e s w o l le i i to two or three times ihcir norm al size with clear pink homogeneous cyto plasm . The hyperplasia was associated with the same cells and appeared Ihm nr*5 ACM 003 6 1C o o c 413 to be an extension of the hypertrophic lesion. The hyperplastic cells w e r e a l s o u s u a lly h y p e rtro p h ic . The m o s t s e v e r e ex am p les of h y p e rp la si. appeared as nodular growths with limited co m p re ssio n of the surrounding normal hepatic tissue. The minor lesions of degeneration, hepatitis, ductule cell proliferation, necrosis and focal lymphoid infiltration seen in the c o n tro l a n im a ls and the T-I and T - I I g roups a r e lesions of spontaneous d i s e a s e and a r e not related to the A r o c lo r 1254. This level of liver d i s e a s is not unusual in rats of this age. Hyperplasia of the transitional epithelium was p re s e n t in the u r i n a r y b la d d e r of an im als fro m the c o n tro l group and each of the test groups. This lesion was usually associated with cystitis. The m o st . severe changes were associated with the presence of mineralized calculi in the bladder lumen. All of the other lesions in o th e r tissues found in these animals are related to spontaneous disease and they are not unusual for old rats. Donovan E . C o rd o n , D. V*. M. , F h . C. Diplomats, American College of Veterinary Pathologists 1001036 ACM CC361 1 000 414 r~ r r- Number of Animals 11 M a l e s 2> C o* o* oo n- TABLE xliic "i 7 fiTEST MATERIAL: A roclor 1254 i Tw o-Y ear Chronic Oral Toxicity Study - Albino Rata Histopathologic Changes Final Sacrifice Organ Examined Group: Control . Findings Incidence Heart Trachea Lung Liver i Stomach Spleen | Kidney Testes, Prostate Adrenal Gland 1I B ra in j. Eye Chronic focal myocarditis Tracheitis Chronic respiratory disease Focal degeneration puctilc hyperplasia Chronic gastritis Hemosiderosis .{ ( Chronic nephritis Testicular degeneration j Periarteritis .; Inflanimallon .Telangiectasis .) Nodular hyperplasia Focal fatty change 1 ! `F o c a l e n c e p h a l i t i s Inflammation * j 3 3 9 1* 2 13 a1 2 2 1 1 J 1 1 2 V Average Grade 1.0 1.0 1.0 1.0 1.0 1.0 1.0 1.0 1.0 1.0 1.0 1.0 1.0 1.0 1.0 I. 0 a 415  I O TABLEXLII1 continued TE ST MATERIAL: A ro c lo r 1254 T w o-Y ear Chronic Oral Toxicity Study - Albino Rate Histopathologic Changes Final Sacrifice Groupt Control Number of A n i m a l s ________ O r g a n E x a m i n e d Findings Average I n c i d e n c e _____________ G r a d e H Females o-j. QD Heart Trachea Lung LIver Stomach Colon Spleen Uterus Kidney Ovary Chronic focal myocarditis Tracheitis Chronic respiratory disease Focal lymphoid infiltration Ductile hyperplasia Focal hepatitis Non-lipid vacuolar change Chronic gastritis Acanthosis - squamous epithelium Parasites Hemosiderosis Metritis Chronic nephritis Focal lymphoid infiltration Cyst , 7 3 13 3 2 1 .2 3 5 1 4 3 6 1 1 2.0 1.0 1.0 L0 1.0 1.0 0.5 1.0 1.0 i.O 1.0 2. 0 1.0 1.0 1.0 0oc 000 Number of Animals M Females TABLE'XLIII continued TEST M ATERIAL; A ro c lo r 1254 , TifO -Y eir .Chronic O ral Toxicity Study - Albino Rata Histopathologic Changes Pinal Sacrifice Group; Control* Organ Examined Adrenal Gland Salivary Gland Findings Telangiectasia Nodular hyperplasia Phcochr oncocytoma Chronic fibrosis and atrophy Incidence 9 4 1 i All other tissues and organs were norm al hislologica lly. 0. 5 'm inim al 1. 0 s slig h t Grading System 2.0 = mild 3. 0 = m o d e r a t e 4.0= severe 5.0 = extreme * D mJk AOh 0 0 3 6 1 *t CD Average G rade 1.0 1.0 1.0 1.0 sn 000 Number of Anirr*-ls II Mali. TTJ O o o nC j uo- l '* T A B L E XLIV* T E S T MATERIAL: A ro c lo r 1254 Tw o-Y ear Chronic Oral Toxicity Study - Albino Rala Histopathologic Changes Pinal Sacrifice Group: I ppm Organ Examined Heart Trachea Lung Liver Pancreas Stomach Spleen Kidney Testes * Findings Chronic focal myocarditis Tracheitis Chronic respiratory disease Congestion Ductile hyperplasia Vacuolar change (fatty) Necrosis . Chronic focal pancreatitis , Peria rlcrilis Chronic gastritis Acanthosis lllccr Hemosiderosis Chronic nephritis Testicular degeneration ft Incidence 5 6 9 1 1 1 1 2 1 2 2 1 5 a 2 - O Average Grade . LO 1.0 1.0 1.0 0. s 1.0 3.0 1.0 2.0 1.0 1.0 1. 0 2.0 2. 0 1.0 -i ) r T A B L E X-LIV continued T E S T M A T ER IA L : A r o c lo r 1254 Two-Year Chronic Ora! Toxicity Study - Albino Rate Histopathologic Changes Final Sacrifice Group: I ppm * Number of A n i m a l s ________ O r g a n E x a m i n e d Testes (continued) Prostate Seminal Vesicle Pituitary Adrenal Gland Parathyroid Gland F i n d i n g s _____________________________ i n c i d e n c e _____ _ Periarteritis Focal calcification Infla mi oat ion Inflammation Congestion Nodular hyperplasia Hyperplasia 2 2 6 2 1 1 1 Average Grade 1.0 2.0 2.0 2. 0 1.0 1.0 1.0 22 Female 40/, Heart Trachea Lung Liver Chronic focal myocarditis Tracheitis Chronic respirstory disease F o c a l l y m p h o i d ' l n i i l l 'r a t i o n 12 16 17 3 1.0 1.0 2. 0 1.0 Foni041 0 0 0 419 C~~^ r r ^ / TABLE XLIV continued T E S T M A T ER IA L : A r o c lo r 1254 Two-Year Chronic O ral Toxicity Study - Albino Rata Histopathologic Changes Final Sacrifice Group; I ppm ' N um ber of Anin*. * Organ Examined Findings ADM 0 0 3 6 1 7 22 Fe*.. a O Liver (continued) Stomach Colon Spleen Lymph Node Kidney Uterus Pituitary Adrenal Gland Ductile hyperplasia Vacuolar change (fatty) Congestion Necrosis Focal Inflammation and acanthosis Parasites Hemosiderosis Abscesses Chronic nephritis Focal calcification Metritis Hyperplasia Telangiectasis Nodular hyperplasia Congestion , l'ocal fatty change .Ku> o .11 o t h e r lii&utia and o r g a n s w e r e n o r m a l h i s t o l o g i e s lly. ( r a i l i u n ` u i Incidence 2 3 1 1 4 2 8 1 B 3 6 4 17 1 1 3 Average Grad 1.0 2.0 1.0 1.0 2.0 1.0* 2.0 1.0 1.0 1.0 1.0 1.0 1.0 1.0 1.0 1.0 Number of Animals 12 M a le s -^5 G G G a* to 6 TABLE XLV T E S T M A T ER IA L : A r o c lo r 1254 * Two-Year Chronic O ral Toxlcily Study - Albino Rats Histopathologic Changes Final Sacrifice G r o u p ; 10 p p m * Organ Examined Heart Trachea Lung Liver 1 ., Pancreas Stomach Spleen * Kidney Ttulcs Findings Chronic focal myocarditis Tracheitis Chronic respiratory disease Pneumonia Vacuolar change (fatty) Ductile hyperplasia Hypertrophy Focal degeneration Chronic focal pancreatitis Chronic gastritis and acanthosis Hemosiderosis Chronic nephritis Testicular degeneration Incidence 7 9 II 1 3 1 1 1 1 1 2 7 1 Average Grade 1.0 2.0 1.0 1.0 1.0 1.0 .0.5 0. 5 3.0 1.0 1.0 1. 0 2. 0 i n K. Number of Animals 12 Male:. T A B L E OCLV c o n tin u e d T E S T M A TER IA L: A ro c lo r 1254 'T w o -Y ear Chronic O ral Toxicity Study - Albino Rate Histopathologic Changes Final Sacrifice G ro u p : 10 p p m ' Organ Examined 'T e ste s (continued) Prostate Sominal Vesicle Adrenal Gland. Thyroid Gland Findings P e ria rte ritis Inflam m ation Inflammation Telangiectasis Focal fatty change Focal hyperplasia Incidence 1 2 2 2 1 1 fcPU lU t/jS ; em aies o> o; Nj NJ oo I H eart Trachea Lung Liver I Chronic focal m yocarditis Tracheitis Chronic respiratory disease Focal lymphoid infiltration V acuolar change (fatty) Nodular hyperplasia 3 7 12 4 1 1 A verage Grade 3.0 .0 1.0 1.0 1.0 1.0 1.0 1.0 1.0 1.0 1.0 3.0 a > <y I TABLE' XLV continued T E S T M ATERIA L: A ro c lo r 1254 T w o-Y ear Chronic O ral Toxicity Study - Albino Rata Histopathologic Changes Final Sacrifice G ro u p : 10 ppm ' Num ber of Animals Organ Examined Findings 12 F e m a le s #w 2> o o *r.<: oIw n Liver (continued) Colon Spleen Lymph Nods Kidney U lem a Pituitary Adrenal Gland Parathyroid Gland Thymus Ductile hyperplasia Telangiectasia Hepatoma Parasites H em osiderosis Congestion Chronic nephritis Focal calcification M etritis Adenoma Hyperplasia Telangiectasis Hyperplasia. Abscess O CO Xk All o th e r t i s s u e s and o rg a n s w e r e n o r m a l h is to lo g ic a l ly . ro f ir illiiin *lu a ln m Incidence 2 1 1 1 2 1 3 1 1 3 1 9 1 1 A verage Grade 1.0 1.0 1.0 1.0 1.0 1.0" 2.0 1.0 1.0 1.0 1.0 1.0 1.0 1.0 AOM 0 0 3 6 2 1 N um ber of A nim ats 11 Males ttj CD ' w CD jg* CD TADLE XLVI T E S T M A TER IA L: A r o d o r 1254 T w o-Y ear Chronic O ral Toxicity Study - Albino Rata Histopathologic Changes . Final Sacrifice G ro u p : 100 ppm* Organ Examined Heart Trachea Lung Liver Small Intestine Spleen Lymph Node Findings Chronic focal m yocarditis Tracheitis Chronic respiratory disease Edema Focal degeneration Vacuolar change (fatty) Ductile hyperplasia Hypertrophy Focal lymphoid Infiltration Portal fibrosis Focal inflammation H em osiderosis Congestion Incidence 3 4 10 3 2 3 3 3 1 1 1 2 1 A verage Grade 2. 0 1.0 1.0 2. 0 1.0 1.0 1.0 2.0 1.0 2. 0 1.0 1.0 1.0 c N um ber of A nim als 11 M ale s TADLE XLVI continued T E S T M ATERIA L: A ro c lo r 1254 Tw o-Y ear Chronic O ral Toxicity Study - Albino R ats Histopathologic Changes Final Sacrifice G ro u p : 100 p p m Organ Examined Kidney T e stes P ro sta te Adrenal Gland. Thyroid Gland Findings Chronic nephritis P e ria rte ritis Inflam m ation Telangiectasis Congestion Hyperplasia Incidence 8 I 5 *2 1 1 Ff0l0a7 IS F em ales - O o o> Mo o<_n ala i H eart Trachea Lung Liver 1 Chronic focal m yocarditis Tracheitis Chronic respiratory disease Edema Focal hypertrophy H ypertrophy F o c a l h y p e r p l%a s ia * 5 6 13 1 1 5 1 A verage G rade 1.0 1.0 2.0 1.0 1.0 1.0 1.0 1.0 2.0 2. 0 I. 3. 0 1.0 I T A B L E* X LV I co n tin u e d T E S T M A TER IA L: A ro c lo r 1254 Tw o-Y ear Chronic O ral Toxicity Study - Albino Rate Histopathologic Changes Final Sacrifice G ro u p : 100 ppnv Number of A n im als Organ Examined A verage F in d in g s _____________________________ In c id e n c e ______________ G r a d e F em ales J o 3 OD Liver fcontinued| Stomach Spleen Kidney Uterus Pituitary Piluit Adrenal Gland Ductile hyperplasia Vacuolar change (fatty) Nodular hyperplasia llepalom a Chronic gastritis Acanthosis Inflam m ation H em osiderosis Chronic nephritis Focal calcification M etritis Hyperplasia Nodular hyperplasia Telangiectasis Nodular hyperplasia Congestion 2 10 * 1 1 2 4 1 5 5 1 3 4 I 3 1 1 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 ACM CC ro All o th e r t i s s u e s and o r g a n s w e r e n o r m a l h ls to lo g ic a lly cr> G r a d i n g S y s t e m tt OO TABLE XLVU TEST M ATERIA L: A ro c lo r 1254 Tw o-Y ear Chronic O ral Toxicity Study - Albino Rata Ifliatopalliologlc Changea of the U rinary B ladder Final Sacrifice Group C Number Sex Examined M II F 14 Findings-:* P ro teln aceo u a plug (34) Focal epithelial hyperplasia (62) T-l (1 pp') M 10 F 19 P ro tein aceo u s plug (326) Diffuse epithelial hyperplasia aaaoclated with diffuse cy stitis (377) T - II (10 ppm) D '. CO T-III (100 ppm) o M 13 F 13 M 10 F 17 Diffuse epithelial hyperplasia and papilloma asso ciated with focal cy stitis (417) Diffuse epithelial hyperplasia associated with diffuse cy stitis (419) None Focal epithelial hyperplasia aaao clated wll)i focal cyslitia (497) Focal epithelial hyperplasia (5) None V VMJ * Individual a n im a l numbe ra a r e ahown in p a r e n t h e s i s . ru G rad in g S y a le m * 1 .0 = m in im a l o r tr a c e 4.0 = severa Incidence 1 1 1 1 1 1 1 1 - lCO A verage G rade 1 3 4 2 2 1 - W Iw C. D etailed D escription of T um or Findings . Tum or data (or individual anim als including location, weight and pathologic classification are presented in Table XLVIII through LL j None of these tum ors could be re la ted to the ingestion of A ro c lo r 1254 and a re considered norm al for a random population of rats this ag e. i F001050 ADM On*'* (H 428 n\ r Animal Number and Sex l-M 2 -M -6-F 47-F 5*1 4B-F C? SO-F 52-F 39-F -F -F 0 in H> ** n * o ou orvi o TABI^E XLVIII T E ST M A TER IA L: A ro c lo r 1254 T w o-Y ear Chronic O ral Toxicity Study - Albino Rats D escription of Tum or Findings Group; Control Location Abdomen Panereas Abdomen Lmph node Abdomen Abdomen Abdomen Abdomen .`ni re n a I g lan d Abdomen Abdomen W eight (gram s) 11.76 H .9 8 35.09 - 88.92 230.00 Sire (cm) - Bxlx2 5x2x2 - 2x2x1 2x2x3 - .t 13 x 11 x 4 1"1 v I I v A C lassific a tio n M am m ary fibroadenoma A denocarcinom a M am m ary fibroadenoma M am m ary fibroadenoma Reticulum cell sarcom a M am m ary fibroadenoma M am m ary fibroadenoma M am m ary fibroadenoma M am m ary fibroadenoma P hcochrom ocytom a Fibroadenom a %<- -- M onths on Test 24 24 24 24 24 7 24 24 24 m non n' r( 'K,- Animal dumber .:nd S**x 11-F X 12-F u '-r ** ! ncatlcn Abdomen Altdorr en Abdomen TADLE XLIX continued TEST M ATERIAL: A roclor 1254 T w o-Y ear Chronic Ora! Toxicity Study - Albino Rata Description of Tum or Findings Group: I ppm W eight (gram s) - Size (cm) - - - C lassificatio n M amm ary adenocarcinoma / f M amm ary fibroadenoma ^ Lipoma ir t * '* ^1* /MV Avn/* v ieii M onths on Test 24 24 24 1 o 0ft1ft53 DC Animal Number an d S(!X 1-M 2-M 3-F 4-F 5-F 6-F 7-F ~l 8 - F : s-f > o XO o1>J O' TABLE XLIX TEST MATERIAL: A ro clo r 1254 Tw o-Y ear Chronic O ral Toxicity Study - Albino Rata Description of Tum or Findings Group: 1 ppm Location Weight (grama) Parathyroid gland - Size ________ <c n t Pituitary - - Abdomen - - Abdomen - - Abdomen Parathyroid gland 8.97 - 2x2x2 - Abdomen 8.86 3x2x2 Abdomen Dorsal cervical region 65.0 209 13x8x2 Pituitary Abdomen Abdomen . - ........... I _ C lassificatio n V A d e n o m a *' <*' C h ro m o p h o b e a d e n o m a 1* M a m m a r y f ib r o a d e n o m a V-" i M am m ary fibroadenoma 1Mammkry adenoma-"" V Adenoma u i M ammary fibroadenoma 1 M amm ary fibroadenoma ''Fibroadenoma ; i Chromophobe adenoma ^ i-` M a m m a r y fib r o a d e n o m a ^ * I K -- /I*----- M onths on Test 24 23 24 24 24 24 24 24 o. o o i) 0 TABLE L TEST MATERIAL) A ro clo r 1254 "* T w o-Y ear Chronic O ral Toxicity Study - Albino Rata D escription of Tum or Findings G ro u p : 10 p p m \nim il Camber .nil Sex 1-M 2-M 3-F 4-F 5-F mJ \ 6 - F & 7-F 8-F nI 9-F o o 0-F # Location Weight (grama) Pancreas - Parathyroid gland - Abdomen - Thyroid Abdomen - - Abdomen - Abdomen Abdomen 86 29 Pituitary Abdomen 28 Pituitary Adrenal gland 7.8 Slxe (cm| - - - 7x8x3 5x5x2 6x 5x 3 - C lassificatio n ^Adenoma p ' /Adenoma U ^M am m ary fibroadenoma 1 Adenoma /M a m m a ry fibroadenoma ^ , M a m m a r y f ib r o a d e n o m a v-'" is Fibroadenom a v F i b r o a d e n o m a *- ' 'Chromophobe adenoma [/Fibroadenoma ^ [/Chromophobe adenoma i / 'T c l a n g l o m a / ' %a t - -t 1 i < i i r M onths on Test 24 24 24 24 i1 1 1 V 24 24 1 24 24 22 g 7A 000 E" 300 gsuiuift 0 Animal Number and Sex 1-F 2-F 3-F 4-M 5-M 6-F 7-M 8-F 9F 10-F o o o u* tb Location Abdomen Abdomen Abdomen Pancreas Abdomen Abdomen Lymph node Pancreas Lymph node Abdomen D TABLE LI T E ST MATERIAL! A ro clo r 1254 Tw o-Y ear Chronic Ora! Toxicity Study - Albino Rats D escription of Tum or Findings G roup: 100 ppm Weight (grama) 48.12 m m % 13.0 52.0 Sire (cm) 5x4x3 18 x 4 x 3 1x2x1 3x3x3 8x5x2 C lassificatio n / F i b r o m a ^' l'"M ammary fibroadenoma ^ M am m ary fibroadenoma ^/Adenoma > /' F i b r o a d e n o m i " l M a m m a r y fib r o a d e n o m a 1_ R eticu lu m c e ll s a r c o m a y ^/A denocarcinom a (/Lym phosarcom a V F i b r o a d e n o m a 1--" % r M onths on Test 24 24 24 24 24 24 13 24 24 24 Animal Number and Sex ll-F 12-F 13-F 14-F 15-F Location Abdumcn Abdomen Abdomen Abdomen Abdomen TABLE LI continued T E ST M ATERIALI A ro c lo r 1254 T w o-Y ear Chronic O ral Toxicity Study - Albino Rata Description of Tum or Flndlnga G roup; 100 ppm Weight (gram s! H I.9 42 209.0 14. 63 Size <c m > 0x8x2 6x4x2 10x9x3 - C lassificatio n '"'Mammary fibroadenom aL / 1 M a m m a ry fib ro ad en o m a i--- Is F i b r o a d e n o m a \ _^ / M a m m a r y f ib r o a d e n o m a *1--' l Fibroadenoma M onths on Teat 24 24 24 24 24 loo ftanuua .u Co U Cl X J on u> O' r r ~t, . . . . ---------------- on ) j- 3 I w - T E S T Jmc. R E P O R T TO MONSANTO COMPANY TW O-YEAR CHRONIC ORAL TOXICITY WITH AROCLOR 1242 IN ALBINO RATS N O V EM 3ER 12, 1971 EBT NO. B7293 I. Introduction At the re q u e st of Monsanto Company, a tw o-year chronic o'ral toxicity study w as conducted using albino ra ts to d e term in e the p o ten tial toxicity of A ro c lo r 1242, Lot No. AK-255. The following re p o rt p re s e n ts the results of this investigation. F/HnfKt? CC363 00C 435 1L S u m m a ry A tw o -y ear chronic toxicity study w ai conducted using albino rats fe d d ie ts c o n ta in in g 1 ( T - l) , 10 ( 7 - I I ) o r 100 (T -C I) ppm A ro c lo r 1242. Food consum ption and body weight gains w ere not altered at any l e v e l o A r o c l o r 1242 fed. The n u m b e r of a n im a ls dying and the tim e a t which the deaths o c c u rre d did not vary among the test and control g ro u rs. H em atological and clinical blood chem istry studies conducted after 3, 6, 9, 12, 13 o r 24 m o n th s did not r e v e a l any a ffe c ts re la ted to A ro c lo r 1242. U rine analyses failed to re v e a l any differences betw een test and control anim als. A t s a c r i f i c e a f t e r 3 t 6 o r 12 m o n th s on t e s t , o rg a n w eights, o r g a n to body weight and organ to b rain weight ra tio s disclosed several ra n d o m ly o c c u rrin g in terg ro u p d ifferen c es. The lack of any consistent dose re la te d resp o n se and the absence of any deleterious histopathologic change c o n firm th a t these d ifferen ces w ere not re la te d to the ingestion of A ro clo r 1242. At the final sacrifice after 24 months on test, the liver weights and liv e r to body weight o r brain weight ratios w ere significantly elevated in f e m a l e s f r o m th e T-XXI g ro u p . H is to lo g ic e x a m in a tio n of the l i v e r s from the T-IH roup revealed several anim als with vacuolar change. Thi* lesio n is m orphologically indicative of fatty degeneration. Specific fat stains confirm ed the presence of fat in these vacuoles. Focal h y p e rtro p h y and fo cal h y p e rp la s ia w ere also found in the livers fro m a n im a ls fed A ro clo r 1242. Fomosa ACM CC3fc33 00' 436 \ V dr I H yprplasia of the urinary bladder was found in animals from the control group and from each of the test groups. This hyperplasia was usually associated with cystitis. The incidences and types of all tum ors w ere about the sam e in all groups, including the control group, and are considered normal for ra ts of this age.. Respectfully submitted, INDUSTRIAL BIO-TEST LABORATORIES, INC. Report prepared by: P h ilip S\ Sm ith, B .S . A ssistant Toxicologist Rat Toxicity Report approved by: Jimjes 5. Plank Senior Croup Leader Rat Toxicity ----- * 'A P a u l li. W rig h t, Ph. D. Section Head, Toxicology November 12, 1971 lm:bbhpdcjl M. L. Keplin^er, M anager, Toxicology aDM 0 0 3 6 3 ` 001 437 HI. P ro ce d u re A. E xperim ental Animals The anim als employed in the te st w ere Charles River strain* alb in o r a t e . F o u r h u n d red r a ts (200 m a le and 200 fem ale) were sele c ted for the experim ent, ear-punched with the anim al number assigned and housed individually in standard wire-bottom ed steel rat cages. Each cage b o re a c o lo r-c o d e d c a rd identifying the r a t with re sp e c t to p ro je c t n u m b e r, d ie ta r y le v e l a s s ig n m e n t, individual a n im a l num ber and sex* B* O rg a n iz a tio n of C ro u p s A s t r u c t u r a l outline of the e x p e rim e n t is given in Table I. TABLE I TEST MATERIAL: A ro c lo r 1242 T w o-Y ear Chronic O ral Toxicity Study - Albino Rats Onfliar of Experim ent Croup Control T-I T-U T-ni N um ber of A nim als M ale Fem ale 50 50 50 50 50 50 50 50 dietary Level fpoml None A dm inistered 1 10 100 * C harles R iver Breeding L aboratories, North Wilmington, Mass. adh 0 0 3 6 FdOlflGO 00! 438 m *' I G ! c 3 T jVtit 5 C* D ie t , F e e d in g and Food Consu m p tio n A ll diet w ere p re p a re d in the c en tral d iet room of this la b o ra to ry . The b a sic ratio n from which all diets w ere constructed w a a s ta n d a rd , p u lv e riz e d stock ra t ration*. The diet for any given t e s t group w as p r e p a r e d by blending the calculated am ount of A roclor 1242 with a pre-w eig h ed portion of the stock ration in a Hobart m ixer. F re s h diets w ere p rep ared each week and every ra t was offered a n am ount of food sufficient for ad libitum feeding. Food consum ption was recorded for five ra ts of each lex in every group w eekly for the f ir s t three months and m onthly for the next nine m onths. T hereafter, periodic spot checks w ere made. D. Body W eights and W eight Cains Initially, the body weight of each ra t in every group was deter* m ined and recorded. Thereafter, individual weighings were made weekly f o r th e f i r s t 13 w e e k s and m o n th ly th e r e a f te r u n til the conclusion of the investigation. . M ortality and Reactions Checks for m ortality and abnormal behavioral reactions were m ad e daily throughout the investigation. F. Hematologic Studies and Urine Analyses Blood studies, including determ inations of hemoglobin concentra tion, h e m ato crit value, erythrocyte count and both total and differential * Purina R at Chow, Ralston Purina Company, St. Louis, M issouri. ACr. CO36 3 RKttflGf 00( 439 l e u k o c y t e c o u n t* , w e r e c o nducted upon five maie* and five fe m a le s fro m b o t h the c o n tr o l and 100 ppm g roup*. J U rin e a n aly se s for the presence of g lu co se, albumin, m ic ro c o p ic e l e m e n t s , a n d d e te r m i n a t i o n s of pH and s p e c i f i c g ra v ity w e re c o n ducted upon u rin e ample* at the sam e time in terv als and from the sam e a n im a ls as tho se em ployed for the blood studies. T h e s e s t u d i e s w e r e con d u cted a f t e r 3, 6, 9, 12, 13, and 24 m o n : of feeding. G. C linical Blood C hem istry Studies D e term in atio n s of blood urea nitrogen concentration (BUN), s e r u m alkaline phosphatase activity (SAP), fa ste d blood glucose concen tra tio n and se ru m glutam ic-pyruvic transam inase activity (SCPT) w ere c o n d u c te d a f t e r 3, 6 , 9, 12, 18, and 24 m o n th s o f fe e d in g upon the s a m e r a t s as w ere the routine blood studies. H. Pathologic Studies When an anim al succumbed during the te st period, a gross autops w a s p e rfo rm ed . In those cases when postm ortem autolysis was not ad v a n c e d , re p re s e n ta tiv e tissu e s w ere taken and p re s e rv e d in ten p ercen t form alin solution for possible future histopathologic study. A f t e r 3, 6 , a n d 12 m o n th s of te s tin g , fiv e a n im a ls of each s e x fro m each group w ere sacrificed and subjected to complete gross paihologi exam inations. F001 ACM CO 3fc3 0 0 1 440 Hr-' B I I T E S T AOO*aJoA*d, nc. 7 A bsolute organ w eights w ere reco rd ed and organ to body weight and organ to b ra in weight ratios computed. The following organs were included: liv er, kidneys, spleen, gonads, h e a rt and brain. These data w e r e then su b je c te d to s ta tis tic a l a n a ly sis. An A n aly sis of V arian ce was conducted first and significant effects disclosed by that treatm ent were fu rth e r studied by " t" -te s ts . Com plete m icroscopic examinations w ere conducted upon the t i s s u e s an d o r g a n s f r o m a ll c o n tro l and 100 p p m g ro u p r a ts s a c r i f i c e d a f t e r 3, 6, o r 12 m o n th s of te stin g . The following tis s u e s and o rg a n s w e r * included in the exam inations: heart, trachea, lungs, liver, p a n crea s, .esophagus, stom ach, sm all intestine (duodenum, jejunum and Ileum ), caecum , colon, spleen, lymph nodes, kidneys, u rin ary bladder> gonads;' p ro state gland, sem inal vesicles, uterus, pituitary gland, adrenal glands, saliv ary glands, thyroid gland, parathyroid glM ^s, skeletal m uscle, sternum , bone, peripheral nerve, spinal cord and brain (cerebrum , cerebellum and pons). The aforem entioned tissues were prepared and stained with H em atoxylin-Eosin stain. A fter two y e ars of feeding, all surviving anim als w ere sacrificed, and subjected to com plete gross pathologie examination. The absolute weights of the liver, kidneys, spleen; gonads, h e a rt and brain were recorded immediately after sacrifie. AO* 0 0 3 6 - " 0( 441 t\diU ai B I C T E S T JaiiMdZMtsi. jmc. 3 M icro sco p ic exam inations were conducted upon tissues and o rg a n s from selected anim als dying during the ex p erim en t and upon all an im als from the final sacrifice. T issues and organs examined were the sam e as those previously m entioned. I. T um or Incidence and C lassification A tabulation of the incidence of tum or form ation in each group w as m ad e a t the conclusion of the investigation. In addition, tum or data for individual anim als including location, weight, size and pathologic classification were recorded. KomOR4 AC* CJ j 0 0 ' 442 BIC -TEST J.U . .\ * 9 IV, R esulta A. Body Weights and Weight Gains The m ale and fem ale body weight data a re assem b led in Table II. T h e d a t a in th is ta b le a ls o in c lu d e the 3, 12 and 24 m o n th to ta l w eight t g a in s . T h e re w ere no significant effects attrib u tab le to the ingestion of the compound. y' i O KOfll 00- 443 r JY. {1 T A B L E II T E S T M ATERIA L: A ro c lo r 1242 T w o-Y ear Chronic O ral Toxicily Study - Albino R ats Body Weight and Total Weight Gain Data Sum m ary of Mean Values )ietary Level of A roclor 1242 (ppm) Sex 012 Body Weight (grama) Week: 3 4. 5 6 7 8 S 10 1 1 12 13 lontrol - M 133 203 245 313 362 373 391 409 424 440 440 449 467 474 F 136 178 190 219 244 254 259 265 270 276 281 278 290 288 1 M . 133 205 254 329 367 377 397 417 432 451 462 481 493 508 F 136 173 197 226 240 253 26B 292 278 280 284 284 288 292 10 M 133 202 251 332 362 372 392 414 428 454 475 481 500 509 F 136 176 196 226 244 254 268 288 276 280 281 284 280 285 100 M 133 203 248 320 365 376 398 416 427 439 453 467 478 4 87 F 136 173 194 225 251 264 272 290 274 275 279 285 283 286 90-Day Total Weight Gain (g r a m s / rat) 341 152 375 156 376 149 354 150 Co . ofc. .Au x no SmtXJtf tietary Level of A ro c lo r 1242 (ppm) Sex Control M F 1M F 10 M F 100 M F TA B L E II continued T E S T M A T ER IA L : A ro c lo r 1242 Tw o-Y ear Chronic O ral Toxicity Study - Albino Rata Body Weight and Total Weight Gain Data Sum m ary of Mean Values 45 6 Body Weight (grama) Month; 78 9 10 1 1 498 533 565 593 622 642 667 688 297 , 310 322 333 345 359 374 383 525 555 580 614 640 665 690 707 302 321 326 333 342 355 367 381 525 553 579 600 627 641 674 693 299 312 328 333 346 354 365 375 504 533 551 580 608 633 662 686 290 307 321 333 347 360 374 388 12 701 390 743 388 706 384 711 379 12-Monlh Total Weight Gain (gram a/rat) 568 254 610 252 573 248 578 243 sv mo suHOi o T O o f Hctary Level of A ro c lo r 1242 (ppm) Sex Control M F 1M F 10 M F 100 M F V TA D LE II c o n tin u ed T E ST M ATERIAL: A ro c lo r 1242 Tw o-Y ear C hronic O ral Toxicity Study - Albino Rata O) O Dody .Weight and Total Weight Gain Data Sum m ary of Mean Values m i/i Body Weight 2 4 -M onth (gramo) T otal Weight Month: Gain r13 14 15 16 17 18 19 20 21 22 23 24 ( g r a m a /r a t) 728 746 759 768 769 767 760 758 739 726 687 642 426 444 466 481 500 515 533 547 551 550 564 551 509 415 767 785 805 800 804 810 800 804 802 800 808 759 428 443 479 468 500 514 523 531 535 538 535 532 626 396 740 750 763 780 784 780 785 783 780 774 796 734 393 406 422 441 462 480 500 519 529 533 537 547 601 411 724 728 723 735 728 736 733 73 725 715 743 6 5 2 428 447 463 467 472 484 4SI 484 485 490 487 485~ 519 349 c /o--Cl Otil t&tHUUtf 1rV^ > L B I O T S T sS & iab yuA i. 13 B. Food Consumption The data obtained fro m the food consumption m easurem ents e c o n d u c te d d u r in g the f i r s t 12 m o n th s of feeding a r e s u m m a riz e d in T a b le III. T hese data revealed no significant difference between test and control ra ts . The periodic checks conducted during the rem ain d er of the investigation also rev ealed no outstanding differences between te s t and control anim als. L -; ACM 0 0 447 C y) . r T A B L E III T E S T M ATERIAL: A ro c lo r 1242 T w o-Y ear Chronic O ral Toxicity Study - Albino Rata Food Consumption Data ! CP O m ui Sum m ary of Mean Values Food Consumption J e ta ry Level of (gram a/rat/seven days) Average Food A ro c lo r 1242 Week C onsum ption ^ (ppm) S e x 1 2 3 4 5 6 7 8 9 10 11 12 13 ( g r a m a / r a t / n e v e n d av a Control M 94 160 175 163 137 137 225 197 204 188 191 194 196 F 73 MO 144 107 104 133 208 154 165 151 146 150 151 174 140 1 M 129 154 165 201 120 191 206 210 232 185 188 189 190 F 91 109 120 164 110 166 124 137 172 140 145 148 145 167 116 10 M 113 132 142 201 120 193 183 184 184 192 196 191 193 F 96 I M 147 131 110 149 102 124 166 144 143 138 144 171 131 100 M 117 149 185 230 161 172 199 172 227 192 186 190 190 F 89 118 129 189 98 114 142 135 180 145 142 139 140 182 135 ir*  BIO-TEST Id m 071 V1 SS'Cf-: T A B L E III continued TEST MATERIAL: A ro clo rl2 4 2 T w o-Y ear Chronic O ral Toxicity Study - Albino Rats Food Consumption Data Sum m ary of Mean Values etary Level of A ro c lo r 1242 (ppm) Sex 4 Food Consumption (gram s/ rat/seven days) * Month: S 6 7 8 9 10 11 12 Control M 196 189 168 147 163 184 179 170 187 F 148 154 136 121 138 152 160 141 127 1 M 180 181 170 189 190 189 196 192 208 F 152 159 141 154 150 148 143 145 159 10 M 184 164 168 197 193 IR8 191 186 177 F 139 147 136 151 144 145 138 142 130 100 M 179 192 189 200 196 186 184 187 167 F 163 M l 160 148 145 144 147 146 145 Average Food C onsum ption (gram s/rat/seven davs) 176 142 188 150 183 141 1B7 ^ -- 149 r U) ... S I C * ; 5 7 ^ K C. M o r ta lity and Reactions A freq u e n cy distribution of natural deaths o ccu rrin g during the in v e stig a tio n a p p e a rs in Table IV. No un to w ard b e h av io ral re a ctio n s w ere noted am ong any of the an im als em ployed in the investigation. 1001072 aCK 003fc`1 O U t 450 i / C Dietary Level (ppm) Sex Control M F 1M F 10 M F 100 M , F TAJ1LE IV T E S T M A TER IA L: A ro c lo r IZ42 T w o-Y ear Chronic O ral Toxicity Study - Albino Rat M ortality Data Frequency Distribution of Deaths Frequency D istribution of Deaths M onths: 1-3 4-6 7-9 10-12 13-15 16-18 19-21 000 2 17 6 000 1 3 5 7 z0 1 1 3 3 7 10 0 1 3 2 4 000 2 I 7 5 0 11 2 0 2 5 000 3 36 7 0 10 1 2 4 8 22-24 9 3 8 5 8 5 10 9 Total Dead N u m b e r T e s t e d * fc 25/35 19/35 25/35 16/35 23/35 16/35 29/35 25/35 iJM^oea not include the five anim als of each sex from every group sacrificed for in terim pathologic stu d ie s. 8 0 0 1 451 1' `s . j SndttA i'^! B I O T S T 2c. 13 D. H em atologic and C linical Blood C hem istry Studies M ean m ale and fem ale hem atologic and clinical blood chem istry i d a t a a r e s u m m a r i z e d in T a b l e s V t h r o u g h DC. V alues for all p a ra m e te rs investigated w ere within the norm al range for the albino ra t. No significant differences between test and control values w ere observed. ( i jt V 00 452 O D ietary Level (ppm) Sex 3 C o n tro l M 14.0 F 9. 1 TABLE V T E S T M ATERIA L: A ro c lo r 1242 T w o-Y ear C hronic O ral Toxicity Study - Albino R ats H em atologic Data Sum m ary of Mean Values Total Leukocyte Count (thousands/rnm ^) M onths 6 9 12 IB IS. 4 10.1 II. 1 9.9 9.4 6.7 7.6 8.8 24 11.2 7.6 Erythnocyte Count (m illions/m m ^) M onth: 36 9 12 18 8. 1 8 .2 8.7 8 .8 7.6 7.5 7.7 7.3 7.8 7.7 24 6.5 6 .8 M 15.6 10.4 9 .7 * 12.5 9.4 9.3 100 F 15.6 9.0 . 7.7 7.8 6.2 6. 4 7.7 8.0 8.0 7.6 7.4 7.6 7.6 7. I 7.9 7.0 7.7 7.2 E in in 3a n * r D ietary Level <ppm) Control 100 TA BLE VI T E ST M ATERIA L: A ro clo r 1242 T w o-Y ear C hronic O ral Toxicity Study - Albino Rata H em atologic Data Sum m ary of Mean Valuea Sex 3 H em oglo b in .C o n cen tratio n ( g / 100 m l) Month: 6 9 12 * 18 24 M 17. 1 17.7 15.7 17.6 16. 1 13.6 F 16.9 17.4 14. 1 16.7 16.4 1 4.6 H em atocrit Value 36 (%> Month: 9 12 18 51 49 48 50 41 50 47 43 46 42 M 1 6 .8 16.9 14.2 15.4 15.6 14.6 F 15.8 16. 1 13.6 15.7 15.5 14. 8 50 48 43 44 41 46 48 41 41 40 24 35 38 37 37 > oT O te* no n ss* UU r>r l s 3i o Ia D ietary Level (ppm) Control 100 Sex 3 M 82.0 F 83.0 T A B L E VII TEST MATERIAL: A roclor I42 T w o-Y ear C hronic O ral Toxicity Study - Albino Rata H em atologic Data 6 86.6 86.6 Sum m ary of Mean Values D ifferential Leukocyte Count (Number of C elia p er Hundred) L ym phocytes N eutrophils Month: Month: 9 12 18 24 36 9 12 80.4 78.8 79.0 65.4 16.0 11.4 18.6 20. 6 86.8 89.0 70.2 61.4 15.4 11.6 II. 8 10.0 18 20. 0 29.2 24 32. 2 36.0 M 89.6 84.4 . 79.8 87.0 66.0 58.4 F 91.4 86.0 82.8 88.4 75.6 65.2 9 .6 15.2 18. 8 11.2 3 3 .0 38. 8 8.4 13.6 17.2 11.2 23.0 33.6 > o X N Oo Irjrj o D ietary Level (ppm ) Control 100 Sex 3 M 0.6 F 0.6 M 0.2 F 0.0 TA B LE VII continued TE ST M ATERIAL: A ro clo r 1242 T w o-Y ear Chronic O ral Toxicity Study - Albino Rats . H em atologic Data Sum m ary of Mean Values Differential Leukocyte Count (Number of Celia per Hundred) M onocytes Eosinophil* Month: Month: 69 12 IB 24 3 6 9 12 0 .0 0 .0 0 .4 0 .2 1.2 1.4 2.0 1.0 0 .2 0.0 0 .0 0 .0 0. 2 1.0 1.0 l.B 1.4 . 0.2 /> IB . 24 0. 8 1.6 0 .6 1.6 0.0 0.0 0.4 0.0 0.0 0.0 0.0 0.2 0.0 0.2 0.6 0.4 1.4 1.4 0. 2 0.4 0 .0 0 .2 1.0 2 .0 1.4 1.0 >o OX o o .u U1 oU* NIvj D ietary Level (ppm) C o n tro l Sex M F M 100 F T A B L E V II continued T E S T M A T E R IA L : A r o c lo r 1242 T w o -Y ear C hronic O ral T oxicity Study - Albino R ats H em atologic Data Sum m ary of M ean Values 1 D ifferential Leukocyte Count (Number of C ells p er Hundred) Basophils Month* 3 6 9 12 Ifi 0.0 0.0 0.0 0.0 0.0 0 .0 0.0 0.0. 0 .0 0.0 24 0.0 0 .0 0.0 0.0 0.0 0.0 0.0 0.0 0.0 0.0 0.0 0.0 0.0 0.0 *;v iK 03 O r. If t AOH 003t rv 1 S 3 1 O I * c r TABLE VIII T E ST M ATERIAL: A r o d o r 1242 T\vo-Y car Chronic O ral Toxicity Study - Albino Rats C linical Blood C h em istry Data Sum m ary of Mean Values D ietary Level (ppTM) Sex Serum Glutam ic-Pyruvic T ransam inase Activity (Dade Units) Month t 3 6 9 12 M 30 Control F 33 48 45 39 . 38 45 42 18 31 32 24 36 30 niood Urea Nitrogen C o n cen tratio n (m g s *U) Month: 3 6 9 12 18 17 15 12 10 14 14 16 15 9 13 24 }r 15 II 100 M 33 35 36 57 39 32 F 39 41 53 40 52 46 15 15 13 14 12 20 17 14 14 11 1! 14 i _n (JO )) o V, ' r BIO-TEST A D ietary Level (ppm) Sex 3 M 128 Control F 130 M 121 100 F 125 T A B L E IX T E S T M A TER IA L: A ro c lo r 1242 T w o-Y ear C hronic O ral Toxicity Study - Albino Rais C linical Blood C hem istry Data Sum m ary of Mean Values Fasted Blood Glucose C o n cen tratio n (m gs %j M o n th : 6 9 12 18 123 89 88 138 118 115 92 134 24 99 109 Scrum Alkaline Phosphatase Activity (King-Arms trong Units) Month: 3 6 9 12 18 28. 6 24.7 21.5 20. 3 16.2 18.9 17. 8 10.6 11.9 16. 8 24 22.3 20. 2 123 129 M5 125 115 118 124 121 135 116 26.4 27.6 23.2 20. 3 17.4 9.6 25.8 11.7 16.7 11.6 13.2 14.2 c* ui wN VO JrttLidwd B I 0 - T S 5 T J a k ta b u*t, 6 E* U r in e A n a ly se s M ein m ale and fem ale urine analyses data are sum m arized in Tables X through XIL No d iffe re n c e s w e re noted betw een the u rin e fro m control and test anim als at the intervals of examination. Forums O nii. 0 0 ( 460  SI0 Ts ST M TADLE X T E S T M ATERIAL: A ro c lo r 1242 T w o-Y ear Chronic O ral Toxicity Study - Albino Rats U rine A nalyses Data Sum m ary of Mean Values J. ! D ietary Level (ppm) Glucose Month: S e x 3 6 9 12 18 24 C o n tro l M n n n n nn F n n n n nn M n n n n nn 100 F n n n n nn C H U lU U -i ^ O^ O CTk Key: n = negative t = tr a c e ; l e s s than 30 m g / 100 m l u rin e 4 I * 30 to 100 m g / 100 m l u rin e 4 2 = 100 to 300 m g / 100 m l u r i n e 3 = 300 to 500 m g / 100 m l u r in e H = m o re than 500 m g / 100 m l u rin e ^ Albumin Month; 3 6 9 12 18 24 n n t. t 42 43 n n n n t 42 n n t t 4 1 44 n n t t t 43 N-I O B IO - i 5 S T.Ja TA B LE XI TEST M ATERIAL: A ro c lo r 1242 Tw o-Y ear Chronic O ral Toxicity-Study - Albino Rata U rine A nalyses Data S u m m a r y oC M ean V a lu e s D ietary Level (ppm) .Control M icroscopic Elements Month: S e x 3 6 9 12 18 24 M N N N N N 4l F NNNNt t pH Month: 3 6 9 12 18 24 7 7 6. 7 7 6 8 8 7 8 66 M N N N N Nt 7 7 7 8 6 6* 100 F N N N N Nt 7 7 6 7 66 I8 U IU U I Key: N= N o r m a l t = trace; le ss than 5 per low power field I - 5 to 10 p e r low p o w e r fie ld 42 = 10 to 15 p e r low p o w e r fie ld 3 = m o r e th a n 15 p e r low p o w e r field OKN) b) GO \ Dietary Level (ppm) Control 100 ---------------------- T A B L E XII TEST MATERIAL: A roclorl242 Tw o-Y e ar Chronic Oral Toxicity Study - Albino Rata Urine A n a l y s e s Data Summary of Mean Values Specific Gravity Month : S e x 3 6 9 12 M 1.029 1.022 1.033 1.027 F 1.020 1.019 1.025 1.024 M 1.021 1.028 1.032 1.024 F 1.022 1.019 1.029 1.029 18 1.042 1.032 1.043 1.027 cn O cn 24 1. 051 1.039 1.030 1.038 S8UIUU O >ci CT> Cv> OO u> o N N t> 2t% d+uiuaX B lO T E 5 T Srnc, 30 F. Pathologic Studies 1. T h r e e Month S a c r i f i c e j a. Cro 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 m ean organ weight and ratio data collected at the t h r e e - m o n t h s a c r i f i c e a r e p r e s e n t e d in T a b l e s XIII th ro ugh XVLII. * Statistically significant differences are designated by I asterisk s following the test group value. Organ weights, organ to body weight and organ to b r a in weight ratios disclosed several randomly occurring intergroup differencei The l a c k of any c o n s i s t e n t dose re l a t e d r e s p o n s e and the absence of any deleterious histopathologic change confirm that these differences were not r e la te d to the ingestion of A ro c lo r 1242. 10 0 1 0 N 6 CC 2tt 0 0 < 464 4I Dietary Level of Aroclor 1242 (ppm) Cont rol 1 10 'T* 100 T A B L E XIII T E S T M ATERIAL: A ro c lo r 1242 T w o-Y ear Chronic O ral Toxicily Study - Albino Rats Organ Weight and Ratio Data Three-Month Sacrifice S um m ary of M ean Values Organ: Liver Organ Weight (g) Males F emales 21.4 13.0 22.3 12.4 23.3 14.4 25.5 14.0 Organ/Body Weight Ratio ( g / 1 0 0 g) Males Fem ales 4. 13 4. 16 4.31 3.92 4.41 4.31 4.80 4.39 Organ/Brain Weight Ratio (g/g) Males Female a 10.3 6.82 10.6 6.59 11.9 7.93 15. 1 7.65 8U IW U j cr> o T A D L E XIV T E S T M ATERIA L: A ro c lo r 1242 T w o-Y ear Chronic Oral Toxicity Study - Albino Rats Organ Weight and Ratio Data Three-Month Sacrifice S um m ary of Mean Values Organ: Kidneys Dietary Level of Organ Weight Organ/Dody Weight Ratio O rgan/B raln Weight Ratio A r o c lo r 1242 (g) ( g / 1 0 0 g) (g/g) _____ ( p p m ) ________________ M a l e s ________ F e m a l e a ____________ M a l e s ________ F e m a l e s ____________ M a l e s F em ales Cont rol 4.03 2.49 0.782 0. 802 1.95 1.31 1 4.06 2.46 0.784 0.772 1.93 1. 30 10 4. 14 2.75 0.786 0.827 2.11 1.52 100 4.24 2.61 0.795 0.817 2.47 1.42 O 466 3 O o > r T A B L E XV T E S T M A T ER IA L : A ro c lo r 1242 T w o-Y ear Chronic O ral Toxicity Study - Albino Rats Organ Weight and Ratio Data Three-Month Sacrifice S u m m a ry of M ean Values Organ: Spleen Dietary Level of Organ Weight Organ/Body Weight Ratio O rg an /D rain Weight Ratio A r o c lo r 1242 (g) ( g / 1 0 0 g) (g/g) (p p m ) ______________ M a l e _______F e m a l e __________ M a l e s _______F e m a l e s __________ M a l e s _______F e m a l e s Control 0.766 0.578 0.150 0. 184 0 . 371 0. 302 l 0.768 0.544 0. 148 0. 171 0. 364 0.287 10 ^ 100 0.756 0.814 0.596 0.528 0.143 0. 154 0. 179 0. 166 0. 385 0.468 . 0. 328 0.288 F o n in R 9 aC*\ r r> orr 1" C I i Dietary Level of A ro c lo r 1242 (ppm) C o n tro l 1 10 100 TABLE XVI TEST M ATERIAL: A ro c lo r 1242 T w o -Y ear Chronic O ral Toxicily Study - Albino R ats O rgan Weight and Ratio Data Three-M onth Sacrifice Sum m ary of M ean Values Organ: Gonads O rgan W eight (gl M ales Fem ales 3.60 0.114 3.51 0.143* 3.50 0.112 3.49 0.112 O rgan/B ody W eight Ratio (g /1 0 0 g) M ales Fem ales 0.698 0.0370 0.681 0.0452 0.666 0.0336 0.656 0.0356 O rg an /B rain W eight Ratio (g/g) M ales Fem ales 1.74 1.66 1.78 0.0599 0.0758 0.0616 2.06 0.0619 rantnso OIM 468 S ta tis tic a lly sig n ifican t d ifferen ce at the 95 p e rc e n t confidence le v el. J ofD i e t a r y L e v e l A r o c lo r 1242 (ppm) . C o n tro l 1 10 100 T A B LE XVII TEST M ATERIAL: A ro clo r 1242 T w o -Y ear C hronic O ral Toxicity Study - Albino R ats O rgan Weight and Ratio Data Three-M onth Sacrifice Sum m ary of M ean Values Organ: Heart O rgan Weight (g) Males Females 1.59 1.05 1.58 1.02 1.55 1.10 1.61 1.05 O rgan/B ody Weight Ratio (g /1 0 0 g) Males Females 0.307 0.339 0. 307 0.320 0.295 0.331 0.302 0.330 O rg an /B rain W eight R atio ( g / g |*1 Males Females 0.767 0.551 0.752 0.540 0.788. 0.608 0.943 0.573 T b lR U W O Tt cn 10 01 001092 Dietary Level of A r o c lo r 1242 (ppm) C o n tro l 1 10 too TA D L E XVIII T E S T M ATERIA L: A ro c lo r 1242 T w o -Y ear Chronic O ral Toxicity Study - Albino R ats O rgan W eight and Ratio Data Three-M onth Sacrifice Sum m ary of Mean Values Organ: Brain O rgan W eight (g) Males Females 2.07 1.91 2.12 1.89 1.97 1.81 1.82 1.83 O rgan/D ody W eight Ratio (g /1 0 0 g) Males Females 0.402 0.616 0.410 0.597 0.375 0.545 0.345 0.576 Total Body W eights of Sacrificed Rats (g) Males Females 518 314 520 318 527 334 534 319  \ a 1C TEST 1m . 1 e. Histopathologic Finding? H istopathologic examination of tissu es and organs taken f r o m a l l a n i m a l s f r o m b o th th e c o n t r o l and 100 p p m g ro u p s w a s c p n d u c te d . T a b l e s XDC and XX l i s t a ll h is to p a th o lo g ic c h a n g e s noted. A ll of the lesions noted in the m icroscopic exam ination of tis s u e s w ere those of spontaneous disease and a re not unusual for'the albino ra t. The m o st frequent findings w ere lesions in the trach ea and lungs, indicating chronic m urine pneumonia. These occurred in the c o n tro l a s w ell as the ra ts fed A ro c lo r 1242. Komrt93 AO* C03fci 00 471 % v_y fy tJ it'J u 'il B I O T S T JiM Aa& nad. $*%c. 33 t a b l e xdc T E S T M ATERIA L: A ro clo r 1242 T w o -Y ear C hronic O ral Toxicity Study - Albino Rats Histopathologic Changes Three-M onth Sacrifice Group: Control N um ber oL A nim als O rgan Exam ined Findings 5 M ales Trachea Lung U rinary Bladder T rac h e itis Chronic respiratory dijease H y p erp lasia 5 Fem ales Lung Chronic respiratory disease Avera Incidence Grad 1 1.0 1 r.o 3 1.0 1 1.0 A ll other tissues and organs w ere norm al histologically. G rading System 0.5 s m inim al 1 .0 = slight 2.0 s m ild 3.0 s m oderate 4.0 severe 5 . 0 extreme Is-' F ftM im ACM CC3 66 0 I 472 3 iO s 3 T 39 TABLE XX T E S T M A T E R IA L : A ro c lo r 1242 T w o -Y e a r Chronic O ral Toxicity Study - Albino Rats Histopathologic Changes Three-M onth Sacrifice Group: 100 ppm Number of Anim als 5 Males 5 Fem ales Organ Examined Trachea Lung Findings T ra c h e itis CFdohcirsoaenlaiicsnetreerssptiitriaatlo ry pneumonia Aver Incidence G ra 2 1. 2 1 l.C A ll other tissues and organs were norm al histolog ically. Grading System 01..50 s= msliignhimt a l 2.0 = m ild 3. 0= moderate 4 .0 = severe 5.0 = extrem e Fnmnss tidtabU al B I O - T E 5 T xe. 40 2. Six-M onth Sacrifice a. G ross Pathologie Findings No outstanding differences w ere noted between test and control anim als. b. O rgan Weight and Organ to Bodv and O rgan to~fcrain Weight ftatio Data ---------------- T h e r e s u l t s of-the s t a t i s t i c al -a n l ay ses-conducted-oa- ab--solute organ w eig h ts, o rg an to body w eight and o rg an to brain weight ra tio s a re su m m a riz ed in T ables XXI through XXVI. O rgan w eights, organ-to body w eight and organ to b ra in weight ratios disclosed several random ly occurring intergroup differences. The lack of any co nsistent dose related response and the absence of any deleterious histopathologic change confirm that these differences w ere not re la te d to the ingestion of A ro c lo r 1242. Fonm% ACH 0 C 3 6 7 ] 00( 474 r, Dietary Level of A ro c lo r 1242 (ppm) C o n tro l I 10 . 100 TA BLE XXI TE ST M A TER IA L: A ro c lo r 1242 T w o-Y ear C hronic O ral Toxicity Study - Albino R ats O rgan Weight and Ratio Data Six-Month Sacrifice Sum m ary of Mean Values Organ: Liver O rgan W eight (g) M ales Fem ales 22.9 13.1 13.8** 9.98* 22.3 13.2 22.0 11.7 O rgan/B ody W eight Ratio (g /1 0 0 g) M ales Fem ales 3.74 2.85** 4.08 4.58* 3.77 3.15 4.23 3.70 O rg an /B rain W eight Ratio (g/gl M ales Fem ales 11.7 6.71 6.86** 11.0 10.8 5.76 6.95 5.94~ o iu u r S t a t i s t i c a l l y s i g n i f i c a n t d i f f e r e n c e a t the 95 p e r c e n t c o n f id e n c e l e v e l . O - Statistically significant difference at the 99 percen t confidence* level; O x* ^j ui AD* 0 0 3 6 7 2 * c , _ \ y r Dietary Level of A ro clo r 1242 (prim) C o n tro l 1 10 100 TA B LE XXII T E S T M A TER IA L: A ro c lo r 1242; T w o-Y ear C hronic O ral Toxicity Study - Albino Rats I O rgan Weight and Ratio Data Six-Month Sacrifice Sum m ary of Mean Values Organ: Kidneys j I O rgan W eight (g) M ales Fem ales 4.04 2.79 3.51 2.44* 3.75 2.49* 3.54 2.33* O rgan/B ody Weight Ratio (g /1 0 0 g) M ales Fem ales 0.664 0.728 0.686 0.730 0.806 0.774 0.790 j I ; ji 0.757 O rg an /B raln W eight R atio <g/gl M ales Fem ales 2.06 t 1.75 1.43 1.41 1.86 1.31 1.74 1.18 titfr-'fcD O A * Statistically significant difference at the 95 percent confidence level. o o ADM 0 0 3 6 7 3 " Ck -4 OS TEST a t oa > r IVi  a Dietary Level of A r o c lo r 1242 (ppm) Cont rol 1 10 ' 100 TA BLE XXIII ` T E S T M A T ER IA L : A ro c lo r 1242 T w o -Y ear C hronic O ral Toxicity Study - Albino R ats * O rgan Weight and Ratio Data Six-Month Sacrifice Sum m ary of Mean Values Organ: Spleen O rgan W eight (g) M ales Fem ales 0.752 0.684 0.754 0.542* 0.796 0.622 0.584 0.488* O rgan/B ody Weight Ratio (g/100 g| M ales Fem ales 0.122 0.196 6.154 0.172 0.142 0.120 0.199 0.159 O rg a n /B ra in W eight Ratio (g/g) M ales Fem ales 0.384 0.350 0.375 0.313 0.394 0. 327 0.288 0.248 6bO V U U l * Statistically significant difference at the 95 percent confidence level. o 2 tv kK 00 o rn w rl 14*>1 () J> D ietary Level of A ro c lo r 1242 (ppm) C o n tro l 1 10 100 T A B L E XXIV T E S T M A TER IA L: A ro c lo r 1242 T w o-Y ear C hronic O ral Toxicity Study - Albino O rgan W eight ant! R atio Data Six-Month Sacrifice Sum m ary of Mean Values Organ: Gonads O rgan W eight (g) M ales Fem ales 3.SS 0.0960 3.44 0.0810 3.55 0.106 3.35 0.0772 O r g a n /Body Weight Ratio (g /1 0 0 g) M ales Fem ales 0.593 0.0279 0.716 0.0253 0.652 0.0335 0.697 0.0251 O rg an /B raln Weight Ratio (g/g) M ales Fem ales 1.81 0.0492 1.71 0.0468 1.76 0.0558 1.65 '0 .0 3 9 2 O 96 CD f tftilfcUOi ( 'S ; fr -TEST 00 f 479 . * Dietary Level of A ro c lo r 1242 |p p m ) C o n tro l 1 10 100 TA B LE XXV T E ST M A TER IA L: A ro c lo r 1242 T w o-Y ear Chronic O ral Toxicity Study - Albino Rata O rgan W eight and Ratio Data Six-Month Sacrifice Sum m ary of Mean Values Organ: Heart * O rgan W eight (g) M ales Fem ales 1.70 1.05 1.49 1.03 1.46 1.06 1.42 0.970 O rgan/B ody W eight Ratio (g /1 0 0 g) M ales Fem ales 0.282 0.302 0.309 0.325 0.267 0.335 0.293 0.314 O rg an /B rain W eight R atio (g/g) M ales Fem ales 0.867 0.538 0.741 0.595 0.722 0.558 0.700 0.492 3> K ** c CD x t ta/*t v. r- Dietary Level of A r o c lo r 1242 (ppm) C o n tro l 1 10 100 % TABLE XXVI T E S T M A TER IA L: A ro c lo r 1242 T w o-Y ear C hronic O ral Toxicity Study - Albino R ats O rgan Weight and Ratio Data Six-Month Sacrifice Sum m ary of Mean Values Organ: Brain O rgan W eight (e) M ales Fem ales 1.96 1.95 2.01 1.73 2.02 1.90 2.03 1.97 O rgan/B ody W eight Ratio (g /1 0 0 g) M ales Fem ales 0.320 0.560 0.415 0.546 0.369 0.597 0.416 0.635 Final Body W eights of Sacrificed Rats <E> M ales Fem ales 613 348 484 317 548 318 488 310 OOz r *o3t Xk. CO o O' c r\ VJ B ' -TEST 2* 4? c. Histopathologic Findings H istopathologic exam ination of tissu e s and organs taken / f r o m a l l a n i m a l s f r o m b o th th e c o n tr o l and 100 p pm g ro u p s was co nducted, T ab les XXVII and XXVIH list all histopathologic changes noted. All of the lesions noted in the m icroscopic examination of tissu es w ere those of spontaneous d isease and are not unusual for the albino r a t. The m o st freq u en t findings w ere lesio n s In the tra c h e a and lungs, indicating chronic m urine pneumonia. These occurred in the contrc as w ell as the ra ts fed A ro c lo r 1242. t Font 103* *0* oo 0 0 481 BI -TEST 45 TABLE XXVII T E S T M ATERIAL: A ro c lo r 1242 ( T w o -Y ear C hronic O ral Toxicity Study - Albino Rats Histopathologic Changes Six-Month Sacrifice Croup: Control N um ber of A n im als Organ Examined Findings Aver Incidence Gra 5 Males Trachea Lung L iv er Skeletal M uscle T rac h e itis Focal tracheitis Focal pneumonitis Hyperem ia Focal pericholangitis Focal inflammation 2 l.S 2 l.C 1 o.s 2 l.'c 1 * 1.0 1 1.0 5 Fem ales Trachea Lung L iv er K idney Focal tracheitis Hyperem ia Hyperem ia Pericholangitis Focal pneumonitis 1. 2 1 1 1 1.0 2.5 1.0 0.5 1.0 All other tissues and organs w ere norm al histologically. Grading System 0.5 s m inim al 1.0 slight 2*0 m ild 1*0 * moderate 4*0 severe 5^0 * extrem e V V 0011O 4 . AC 00( 4e2 *L B I O - T E S T a o *a fit-UArf, $4 49 > TABLE XXVIE T E S T M ATERIAL: A ro c lo r 1242 Tw o-Y ear C hronic O ral Toxicity Study - Albino Rats Histopathologic Changes Six-Month Sacrifice Group: 100 ppm N u m b er of Animals Organ Examined Findings Avera Incidence Grad 5 Males Trachea Lung 5 Fem ales Trachea Lung T rach eitis Focal tracheitis Foeal pneumonitis H yperem ia Focal tracheitij Focal pneumonitis H yperem ia 12 2 3 2. 1* 1 1- 1.0 0.5 1.5 1.0 1.0 0.5 2.0., All other tissues and organs w ere norm al histologically. Grading System , 0 . 5 = m inim al 1.0 = slight 2.0 = mild 3.0 = m oderate 4.0 = severe 5.0 = extrem e . HnmiBS AC* C03tdC 00C 483 5 I *T 5 T a** 50 3* T w e lv e -M o n th S a c rific e a.. G r o s s P a th o lo g ie F in d in g s / G ross pathologic findings among te st animals were not significantly different fro m those noted in control anim als. b. Organ Weight and Ratio Data The m ean organ weight and ratio, data collected at the tw elve-m onth s a c rific e a re presented in Tables XXIX through XXXIV, Statistically significant differences are designated by a ste risk s following the test group value. O rgan w eights, organ to body w eight and organ.to b ra in weight ratios disclosed several randomly occurring intergroup differences.' The lack of any co n sisten t dose related resp o n se and the absence of any deleterious histopathologic change confirm that these differences were not re la te d to the ingestion of A roclor 1242. r IlllU U d Dietary Level (ppm) C o n tro l 1 53 io 100 O O b o 0LT01 o o T A B L E XXIX T E ST M ATERIAL: A ro c lo r 1242 T w o-Y ear Chronic O ral Toxicity Study - Albino Rats Twelve-Month Sacrifice O rgan Weight and Ratio Data Sum m ary of Mean Values Organ: Liver O rgan Weight M alea (g) Fem ales O rgan/B ody Weight Ratio (g/100 g) M ales Fem ales 22.1 15.5 3.79 3.52 22.7 13.7 3.45 3.33 22.4 14.4 3.48 3.44 26.3 14.4 3.78 3.59 O rgan/B rain Weight Ratio Cfi/fil M ales Fem ales 10. 8 7.72 10.4 7.05 10.6 12.4 7. 39 7. 16 l1 t-.Ii l>i -I \ (' TA B LE XXX T E S T M A T E R I A L : A r o c l o r 1Z4Z Tw o-Y ear Clironic Oral Toxicity Study - Albino Rats Twelve-Month Sacrifice Organ Weight and Ratio Data Sum m ary of Mean Values Organ: Kidneys Dietary Level (ppm) Organ Weight (g) Males Females Organ/Body Weight Ratio (g /1 0 0 g) Males Females Control 4.04 3. 19 0.692 0. 738 rrj- s i O O*. 1 4.31 2.93 0. 656 0.735 10 4.27 3.24 0. 662 0. 779 100 4.98* 3.01 0.716 0.745 * Statistically significant difference at the 95 p e rc en t confidence level. O rgan/B raln Weight Ratio (g/g) Males F em ales 1.97 1.58 1.97 1. 51 2. 02 1.66 2. 33 1.50 Xk. CD o\ )> it v> in N / T A B LE XXXI T E ST M ATERIAL: A ro c lo r 1242 T w o-Y ear Chronic O ral Toxicity Study - Albino Rats Twelve-Month Sacrifice Organ Weight and Ratio Data Sum m ary of Mean Values Organ: Spleen Dietary Level ____ <ppm >_________ Control Org an Weight Males <g> Females 0.788 0.796 Organ/llody Weight Ratio (fi/100 g) Males Females 0. 133 0.183 O rgan/Brain Weight Ratio tg/g> Males Females 0.380 0.396 1 1.000* 0.600 0. 152 0. 153 | 10 0.868 0.664 0. 136 0.160 100 i 0.968 0. 570 0. 138 0. 145 O> - - oc CO -o * S t a t i s t i c a l l y s i g n i f i c a n t d i f f e r e n c e a t th e 95 p e r c e n t confidence' l e v e l . * *. 0.458 0.412 0.454 0.307 0. 341 0.285 t C3 fit i/l V (A 9CTJ fO Dietary Level (ppml Control 1 10 100 TA BLE XXXII TE ST M ATERIAL: A ro c lo r 1242 T w o-Y ear Chronic Oral Toxicity Study - Albino Rats Twelve-Month Sacrifice Organ Weight and Ratio Data Sum m ary of Mean Values Organ: Gonads Organ Weight (g) Males Females 3.46 0. 116 3.47 0. 0938 3.00 0. 14! 3.67 0. 122 Organ/Body Weight Ratio (g/100 g) Males Females 0. 596 0.0275 0. 529 0.0239 0.457 0.0332 0. 531 0.0305 Organ/Brain Weight Ratio (g/fi) Males F em ales 1.70 0. 0574 1.59 0.0483 1.40 1.72 0.0719 0.0608 ^ Statistically significant difference at the 95 percent confidence level. Vi f. n --i in in lx J i* V* v in 4. o 000 4 8 $ C" ) J vuf T . J , . i c 5 i - 1 n r'^r i,P*C Dietary Level (opml Control 1 10 100 F0011I1 O O o*t 0V0O 3> TA B LE XXXIII TE ST M ATERIAL: A ro c lo r 1242 Tw o-Y ear Chronic O ral Toxicily Study - Albino Rats Twelve-Month Sacrifice Organ Weight and Ratio Data Sum m ary of Mean Values Organ: Heart Organ Weight (g) Males Females 1.71 1.69 - 1.23 1. 18 1.68 1.29 1.87 1.19 Organ/Body Weight Ratio (g/100 g) Males Females 0.293 0.286 0.258 0.298 0.263 0.312 0.268 0.298 O rgan/B rain Weight Ratio (g/g) Males F em ales 0. 835 0.776 0. 609 0. 610 0.799 0. 878 0. 663 0. 591 Ul/*l 7 Dietary Level (ppm| Cont rol 1 to 2 100 T A n L E XXXIV T E S T MATERIAL: A ro c lo r 1242 Tw o-Y ear Chronic O ral Toxicity Study - Albino Rats Twelve-Month Sacrifice Organ Weight and Ratio Data S u m m ary of Mean Values Organ: Drain Organ Weight Males (e) Females 2.04 2.02 2. 19 1.95 2.11 1.95 2. 14 2.00 Organ/Dody Weight Ratio ( c / i o o g) Males Females 0. 351 0. 474 0. 334 0. 516 0. 329 0.473 0. 310 0. 508 Final Body Weight of Sacrificed Animals (grains) Males * Fem ales 5B4 439 660 431 642 425 698* - .409 F ,ft0 1 1 1 2 S ta tistic a lly significant difference at the 95 p e rc e n t confidence level. S, On -- IX o t*. o in in -I I II % 5 V. Ua1 rN J V tO T E5 T /*. c. Histopathologic Findings Histopathologic examination o! tissu es taken from e r a t s a c r i f i c e d f r o m the c o n t r o l and 100 ppm g r o u p s a f t e r twelve-mont; \ of testing was conducted. Tables XXXV and XXXVI list all histopathologic chaj noted. All of the lesions noted in the m icroscopic examir.ati w e r e those of spontaneous d is e a s e and cannot be re la te d to the-ingestio A ro c lo r 1242. V ' 1 Fooiina OCn 4 9 1 B . J T E 5 T jfaa>ta^uuf Sna. 5< TABLE XXXV i T E S T MATERIAL: A ro c lo r 1242 Two-Year Chronic Oral Toxicity Study - Albino Rats Histopathologic Changes Number of Anim als 5 Malos 4 5 Fem ales Twelve-Month Sacrifice Group: Control Orean Examined Trachea Lung U rin a ry Bladder Trachea Lung Colon Findings Incidence Tracheitis Chronic respiratory * Cdailsceualusse 1 2 1 TCrharcohneicitirse s p ira to ry disease Paras ites * 1. 1 AC1 Ail other tissues and organs were normal histologically. Grad:.".? System 0.5 = minimal 1.0 = slight 2.0 = mild 43 ..00 ss mseovdeerrea t e 5.0 s extreme K,n n i i i 4 ACM 003661 00 ( 4 9 2 T A 3 L E XXXVI ,, T E S T M A T E R IA L : A ro c lo r 1242 Tw o-Y ear Chronic O ral Toxicity Study - Albino Rats Histopathologic Changes Twelve-M onth Sacrifice Croup: 100 ppm NAunmimbearlsof ExOarmgainned Finding s Incidence 5 Males LTur ancgh e a PL aivnecrreas PKiidtunietay ry Adrenal T ra c h e itis FFCCooohccnr oaagnlleislacyttmiroroepnpshhpoyiidr a itnofriyl t rdaist ieoans e Chromophobe hyperplasia HNeomdualcaorchyyspt erplasia 1 4 1 IIl lI . 5 Females Trachea Lung TCrharcohneicitirse s p ira to ry disease 1l CA v , j] 1 1 1 1 I .11 A ll other tissues and organs were norm al histologically. Gradir.g Svstem 0 .5= minimal 1.0 = slight 2. 0 = m ild 3 .0 = moderate 4. 0 = severe 5. 0 = extrem e. OC30 9 , 00( 494 1001116 jtidruiuG l B I T E S 7 4. Final Sacrifice a. Gross Pathologic Findings G ross 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 s a c rif ic e a r e p re s en ted in Tables XXXVII through XLII. Statistically significant d iff e r e n c e s a r e designated by a s t e r i s k s following the te s t group value. The absolute liver weight and liver to body or b ra in weigft r a t i o s w e r e s i g n i f i c a n t l y e v a lu a te d in f e m a le r a t s fed 100 ppm A r o c l o r 1242. Statistical evaluations of other organ weights, organ to body weight and orga .to b rain weight ratios disclosed sev eral randomly occurring intergroup dif fe re n ce s. The lack of any consistent dose re la ted response indicates that t h e s e d if f e r e n c e s w e r e not r e l a t e d to the inge stion of A r o c lo r 1242. V Fnm117 t0" CC369` n p 495 F001118 stary Level (ppml Control 1 10 100 TABLE XXXVII TEST MATERIAL: A rocloi 1242 Two-Year Chronic Oral Toxicity Study - Albino Rata Organ Weight and Ratio Data a Summary of Mean Values Final Sacrifice Organ: Liver Organ Weight <g)' Male* Females Organ/Body Weight Ratio (g/100 g) Males Females ZZ. 0 21.9 22. 3 25.6 16.3 IS.? 17. 1 22.4** 3.47 2.93 3. 18 3.95 3.05 3.00 3. 19 4.82** * Statistically significant difference at the 99 percent confidence level. C VO CTv % rt O rgan/B rain Weight Ratio (g/g) Males Female a 10. 10 8. 41 9.97 8.03 10. 20 8. 50 11.90 11. 60** a I C; etary Level (npm) Control 1 10 100 TA B LE XXXVIII TEST MATERIAL: A roclor I242 Two-Year Chronic Oral Toxicity Study - Albino Rata Organ Weight and Ratio Data Summary of Mean Values Final Sacrifice Organ Weight (g) Males Females 5.57 3.48 6.1) 3.45 Organ: Kidneys Organ/Body Weight Ratio (g/100 g) Males Females 0.877 0.646 0. 820 0.670 5.63 5.44 3. 43 3.43 0.816 0.835 0.644 0. 725 O rgan/B rain Weight Ratio (g/g> Males Females 2. 57 1.79 2.78 1. 76 2. 56 2.52 1.71 l. 79 > NO ' I I 1001119 OCK? 02UU0J etary Level (ppm) Control 1 10 100 C o u0>0 k. o o o u TABLE XXXIX TEST MATERIAL: A ro c lo r 1242 Two-Year Chronic Oral Toxicity Study - Albino Rato Organ Weight and Ratio Data Summary of Mean Values Final Sacrifice Organ Weight Males <gl Females 1. 15 0.96 1.26 0.81 1.08 0.82 1.07 0.65 Organ: Spleen Organ /Body Weight Ratio ( g / i o o g) Males Females 0. 182 0. 169 0. 181 0. 158 0. 158 0. 165 0.153 * 0. 140 * O r g a n / B r a l n Weight Hat (e/g) Males Fcmal 0. 520 0.572 0. 49 0. 14! 0.495 0. 499 0.40* 0. 331 / A ctary Level (ppm) Control 1 10 100 O' o I n .u x vo VO o o I TABLE XL TEST MATERIAL: A ro c lo i 1242 Tw o-Year Chronic Oral Toxicity Study - Albino Rata Organ Weight and Ratio Data Sum m ary of Mean Values Final Sacrifice Organ Weight Males <g> Females 2.52 0 . 123 1.20 0. 102 Organ: Gonads Organ /Body Weight Ratio (b / 1 0 0 e > Males Females 0.397 0.0222 0.424 0.0205 3.00 3.31 0. 126 0. 129 0.437 0.514 0.0237 0.0278 1. i. Ul O Ml t/i O rgan/B rain Weight Ratio (g/g) Males Females 1. 15 1.46 0. 062 0.0523 1.40 1.55 0.0625 0.0671 4O*.' F0011 -) 4 `J itary LeVel (ppm) Control 1 10 100 TABLE XLI TEST MATERIAL: A ro c lo r 1242 Two-Year Chronic Oral Toxicity Study - Albino Rata Organ Weight and Ratio Data Summary of Mean Values Final Sacrifice Organ Weight Males (g) Females Organ: Heart Organ/Body Weight Ratio ( g /1 0 0 g) Males Females 1.87 1.54 0.294 0.288 2.30* 2.08* 2. 19* 1.51 1.59 1.41 0.307 0. 303 0.335 0.292 0.298 0.303 S ta tis tic a lly significant d ifferen c e at the 95 p e r c e n t confidence level. Statistically significant difference at the 99 percent confidence level. Ln o o ADM 0 0 3 6 9 7 O rgan/B rain Weight Ratio (g/g) Males Females 0. 860 1.040** 0.959* 1.010* 0. 79r 0. 770 0. 788 0. 74 1 cn oi ) r Dietary Level (ppm) Control 1 10 100 TABLE XLII T E ST MATERIAL: A ro c lo r 1242 Two-Year Chronic Oral Toxicity Study - Albino Rais Organ Weight and Ratio Data Summary of Mean Values Final Sacrifice Org an Weight (B) Males Females . 2. 18 1.95 2.20 1.96 2. 18 2.01 2. 14 1.91 Organ: Brain O rgan/D ody Weight Ratio (g/100 g) Males Female 0. 342 0. 362 0. 294 0. 388 0. 313 0. 379 6. 330 0.415 Final Body Weight of Sacrificed Animals (grams) Males Females 642 551 759 532 734 547 652 485 o "X oo oa E S H tH ij TOS 0 0 t c. Histopathologic Findings Histopathologic examination of tissues and organs :ak / f r o m a ll a n im a ls s a c rifice d after 24 months on te st was conducted Tables XLIII through XLVI list all histopathologic cha noted. Table XLVII contains the re su lts of the histopathologic examina: of the urinary bladders. Sign ific ant l i v e r i n j u r y was found in a n im a ls fed ICO pp A r o c l o r 1242 (T-III). The compound a sso c iate d lesions consisted of v a c u o l a r c h a n g e , foc a l h y p e r t r o p h y and fo c a l h y p e r p l a s i a . In a d d it io n , tl w ere lesions of inflammation, necrosis, fibrosis and minor degeneration th is g ro u p which, although seen in the c o n tro ls and low er te s t g r o u p s , we m o re sev e re and frequent in the T-III group. The vacuolar change was not seen in the control animal* b u t w a s o b s e r v e d o c c a s i o n a l l y in l i v e r f r o m T - I l ppm) and 7 - U (10 ppm, a n i m a l s . The v a cu o la r change was o b s erv ed freq u en tly in the T-IH anirr.a This lesion is morphologically indicative of fatty degeneration. Form alin frozen sections of livers from representative animals which displayed v a c u o l a r c h a n g e s w e r e s t a i n e d with Oil R e d O to r e v e a l the p r e s e n c e of fa* The vacuolar lesion in the cytoplasm of these cells was positively identifie as fat. The hypertrophic change found in the liver was focal and often lim ited to the central lobular a rea where groups of cells were swolle to two o r th re e tim es their norm al size with clear pink homogeneous cytap 1001124 oocAC OC309S 502 The h y p e rp la s ia was asso ciated with the sam e cells and appeared to be extension of the hypertrophic lesion. The hyperplastic cells were also u s u a lly h y p e rtro p h ic . The m o st s ev ere exam ples of hyperplasia appear as nodular growths with limited com pression of the surrounding n o rm al hepatic tissue. p ro liferatio n , n e c ro sis and focal lymphoid infiltration seen in the control a n im a ls and the T -I and T-II groups are lesions of spontaneous disease a a r e not re la te d to the A ro clo r 1242. This level of liver disease is not unusual in old animals. Hyperplasia of'the transitional epithelium was present in the u r in a r y bladder of animals from the control group and from each oj the test groups. This lesion was usually associated with cystitis. All of the other lesions in the other tissues found in the anim als are related to spontaneous disease and they are not unusual for r a t s of th is ag e. Donovan E. G o r d o n , D. V. M. , Ph. D. Diplomate, A m e ric a n College of Veterinary Pathologists ADH C OOU 33 1:001125 > TABLE XLIII TE ST MATERIAL: A ro clo r 1242 Tw o-Y ear Chronic Oral Toxicity Study - Albino Rats Histopathologic Changes Final Sacrifice Group: Control Number of . A n i m a l s ________ O r g a n E x a m i n e d 11 M a l e s Heart Trachea Lung Liver Stomach Spleen Kidney Te ate s * Prostate Adrenal Gland cfei i Brain Eye uoo> o Findings Chronic focal myocarditis Tracheitis Chronic respiratory disease Focal degeneration Ductile hyperplasia Chronic gastritis Hemosiderosis Chronic nephritis Testicular, degeneration Periarteritis Inflammation Telangiectasis Nodular hyperplasia Focal fatty change Focal encephalitis Inflammation Incidence 3 3 9 1 2 1 3 8 2 2 1 1 1 1 1 2 V: ut i: o C n U Average Grade 1.0 1.0 1.0 1.0 1.0 1.0 1.0 I. 0 1.0 1.0 1.0 1.0 1.0 1.0 1.0 1.0 I, i t; t.' i k O' OOC 504 r O/ > Number of Animals 14 F e m a l e s 3 Ow V*. O--* o* tn ^ 7O7. U-Ji *w o N* TABLE XLIII continued TEST M ATERIA L: A r o c l o r 1242 Tw o-Year Chronic Oral Toxicity Study - Albino Rats Histopathologic Changes Final Sacrifice Group: Control Organ Examined Heart Trachea Lung Liver Stomach Colon Spleen Uterus Kidney Ovary Findings Chronic focal myocarditis Tracheitis Chronic respiratory disease Focal lymphoid infiltration Ductile hyperplasia Focal hepatitis Non-lipid vacuolar change Chronic gastritis Acanthosis - squamous epithelium Parasites IIcinosidc rosis Metritis Chronic nephritis Focal lymphoid infiltration Cyst Incidence 7 9 13 3 2 1 2 J 5 1 4 3 6 1 1 Average Grade 2.0 1.0 1. 0 1.0 1.0 1.0 0.5 1.0 1.0 1.0 " . l.o 2.0 1.0 1.0 1.0 ------------------------------- i * 9 0 s , n n 8 1 1 0 1 /.!! Number of Animals 14 F e m a l e s * TABLE XLIII continued T E ST M ATERIAL: A r o c lo r 1242 Tw o-Y ear Chronic O ral Toxicity Study - Albino Rats Histopathologic Changes Final Sacrifice Group: Control' Organ Examined Adrenal Gland Salivary Gland Findings Telangiectasis Nodular hyperplasia Chronic fibrosis and atrophy Incidence 9. 4 1 All other tissues and organs were norm al histologically. 0.5 = minimal 1.0 = slight Grading System 2.0 = mild 3.0 = moderate 4.0 = severe 5.0 = extreme AUh 0 0 3 7 0 3 Average Grade 1.0 1.0 1.0  I TABLE x u v T E S T M ATERIAL: A ro c lo r 1242 Tw o-Year Chronic O ral Toxicity Study - Albino Rais Histopathologic Changes Final Sacrifice Group: I ppm * 6 u u u :i Number of Average A n i m a l s _________O r g a n E x a m i n e d ____________________F i n d i n g s ________ ._____________________in c id e n c e ______________ G r a d e Heart Trachea Lung Liver Stomach Spleen Kidney Testes Prostate Adrenal Gland Chronic focal myocarditis Tracheitis Chronic respiratory disease Focal lymphoid infiltration Cirrhosis Congestion Chronic gastritis and acanthosis Hemosiderosis Chronic nephritis Calcification Periarteritis Testicular degeneration Inflammation Telangiectasis Nodular hyperplasia 5 9 12 1 I 1 2 4 9 1 2 1 1 2 1 1.0 2.0 1.0 1.0 1.0 1; 0 1.0 2. 0 2.0 l. 0 2.0 1.0 4. 0 1.0 2. 0 )ft0 Ln o i-JI v; T A B L E XI-.IV con tinue d T E S T M AT ER IA L : A r o c l o r 1242 Two-Year Chronic Oral Toxicity Study - Albino Rata Histopathologic Changes Final Sacrifice Group: 1 ppm * Number of Animals Organ Examined Findings 14 F e m a l e s Heart Chronci focal myocarditis Trachea Tracheitis Lung Chronic respiratory disease Liver Ductile hyperplasia Pancreas Chronic focal pancreatitis 5 Stomach Chronic gastritis Ulcerative gastritis Acanthosis ft O> * Spleen Kidney Uterus Hemosiderosis Chronic nephritis Met ritis O oo oo / U1 o 00 Adrenal Gland Telangiectasis All o th er tis s u e s and organa w e r e n o r m a l histologically, Incidence 6 7 13 3 2 2 1 2a & 1 10 Average G rade LO 1.0 LO 1.0 1.0 1.0 1.0 1.0 2.0 1.0 1.0 1.0 c TABLE XLV T E S T M A T E R IA L : A r o c l o r 1242 Tw o-Year Chronic O ral Toxicity Study - Albino Rats Histopathologic Changes Final Sacrifice G r o u p : 10 p p m * Number of Animals 13 Males Organ Examined Heart Trachea Lung Liver Pancreas Stomach U Oo oX Spleen Kidney Testes Findings Chronic focal myocarditis Tracheitis Chronic respiratory disease Focal hypertrophy and hyperplasia Hypertrophy Vacuolar change (fatty) Ductile hyperplasia C h r o n i c fo<.at p a n c r e a l i t s Acanthosi s Inflammation, ulceration and ncc rosis Hemosiderosis Chronic nephritis Testicular degeneration Periarteritis Incidence 6 7 9 1 1 2 1 3 6 l 7 10 2 3 'Average Grad 1.0 1.0 2. 0 1.0 1.0 i: o 2. 0 1.0 1.0 1.0 1.0 2. 0 3. 0 3. 0 1. Number of Animals 13 Males 13 F em ales r> o o Ui -J o ln TABLE XLV continued TEST MATERIAL: Aroclor |242 Tw o-Year Chronic Oral Toxicity Study - Albino Rats Histopathologic Changes Final Sacrifice G r o u p : 10 p p m ' Organ Examined Prostate Adrenal Gland Heart Trachea Lung Tongue Stomach Spleen Lymph Node Kidney Uterus Adrenal Gland Findings Infiammai ion Telangiectasis Medullary hyperplasia Nodular hyperplasia Chronic focal myocarditis Tr ac he it i s Chronic respiratory disease Periarteritis Chronic gastritis and acanthosis Ulceration Hemosiderosis Edema Chronic nephritis Metritis Telangiectasis Nodular hyperplasia Incidence 2 4 1 2 1 5 9 1 S 1 5 i 6 2 a 1 Averag Gradt 3. 0 1.0 1.0 I. a 1.0 i. a 1.0 2. 0 1.0 I. 0 2. 0 1.0 1.0 1.0 1.0 I. 0 Korn132 000 000 C lH U M I Number of Animals 6 Males * . n* o uo TABLE XLVI T E S T M ATERIAL: A r o c lo r 1242 Tw o-Year Chronic O ral Toxicity Study - Albino Rata Histopathologic Changes Final Sacrifice G ro u p : 100 p p m ' Organ Examined Heart Trachea Lung Liver Pancreas Testes Stomach Spleen Lymph Node Kidney Findings Chronic focal myocarditis Tracheitis Chronic respiratory disease Focal degeneration Focal hypertrophy Hypertrophy Vacuolar change (fatty) Periarteritis Periarteritis Chronic gastritis and acanthosis Periarteritis 1l e m o s i d e r o s i s Periarteritis Chronic nephritis Incidence 3. 3 1 1 1 3 1 3 I 1 1 1 4 [ * i i Average Grade 1.0 2. 0 1.0 1.0 1.0 1.0 1.0 3. 0 2.0 1.0 ' . 2.0 1.0 3. 0 2. 0 I t l ( ? / \ Number of Animala 6 Males 14 F e m a l e s rr! Vd jfi O O o > o v_n ro o o It* TABLE XLVI continued T E S T M ATERIAL: A r o c lo r 1242 Tw o-Year Chronic O ral Toxicity Study - Albino Rats Histopathologic Changes Final Sacrifice G ro u p : 100 ppnv * Organ Examined Prostate Adrenal Gland Salivary Gland Eye Findings Inflammation Focal fatty change Focal chronic inflammation Inflammation Incidence 1 I 1 1 Heart Trachea Lung Liver Chronic focal myocarditis Tracheitis Chronic respiratory disease Focal degeneration Focal hyperplasia Focal hypertrophy Hypertrophy Nodular hyperplasia Focal chnlangifJicpatitis a4 6 3 2 2 3 1 1 V / r ^ 4 f " Average Grade 3. 0 1.0 1.0 1.0 1.0 1.0 1.0 1.0 1.0 1.0 2. 0 1.0 1.0 ;V, \ TABLE XLVI continued T E S T M A T ER IA L : A r o c l o r 1242 # Tw o-Y ear Chronic O ral Toxicity Study - Albino Rats Histopathologic Changes Final Sacrifice G r o u p : 100 ppm Number of Animals Organ Examined Findings 14 F e m a l e s Liver (continued) Pancreas Stomach Spleen Lymph Node Kidney Lite r u s Adrenal Gland Focal hepatitis Hyperplasia Vacuolar change (fatty) Chronic focal pancreatitis Chronic gastritis Acanthosis Ulcerative gastritis Ulcer Hemosiderosis Congestion Chronic nephritis Metritis Telangiectasis Nodular hyperplasia Acanthosis j UQi COO WOV Ln All o t h e r t i s s u e s and o r g a n s w e r e n o r m a l h is to lo g ic a l ly . Uh-*i Grading System Incidence I I 11 1 2 2 1 1 4 1 7 2 8 4 1 Average Grati 1.0 3. 0 1.0 1.0 1.0 1. (1 1.0 1. 0 2. 0 1.0 1.0 1.0 1. o 1.0 1.0 > ; TA n i.E XI.VII TE ST MATERIAL: A roclor 1242 Tw o-Year Chronic Oral Toxicity Study - Albino Rats Histopathologic Changes of the U rinary Bladder Final Sacrifice Group C T-I (1 ppm) Number Sex Examined Findings M 11 F 14 P r o te in a c e o u s plug (34) F o c a l epith e lial h y p e r p la s ia (62) W 12 F 13 P ro tein ac eo u s plug (582) Diffuse epithelial hyperplasia associated with diffuse cystitis (566) Diffuse epithelial hyperplasia associated with dif f u se c y s t i t i s (5H0) None o 2 C3 % U1 H T - 11 (10 ppm) o X T- Ml 1 100 ppn) o Ui hi M F M F 11 13 6 13 Diffuse epithelial hyperplasia associated with diffuse cystitis (651) Diffuse epithelial hyperplasia associated with diffuse cystitis anti a proteinaceous plug (655) None Proteinaceous plug (744) Focal epithelial hyperplasia (767) I n d i v i d u al animal numbers a rc shown in pa rrn lh c s c s. Gratti ng System 1.0 minimal or -trace 4.0 - sevcre ------ Incidence 1 i 1 1 1 1 1 1 1 " " " "~=" |C F, {, Ave rage Grade 1 2 1 3 1 - 2 _ 6 k TEST BI O - T EST J a m * G . Detailed Description of Tumor Findings Tumor data for individual animals including location, weigh: and pathologic c las s ific atio n a r e presented in Table XLVUI through LI. None of these tum ors could be related to the ingestion cf A rccl 1242 and a r e c o n s i d e r e d n o r m a l for a ra n d o m population of rats this age Il1 # ( f n n i i ^ 7 ao,< 0 0 3 7 1 0 0 515 j Animal 'um ber nd Sex 1-M 2 -M ** lb-F Location Abdomen Panereaa Abdomen 47- F 48-F 50- F 52-F -F 1- F o> Dt. oO \->--J1 r Lymph node Abdomen Abdomen Abdomen Abdomen Adrenal gland Abdomen T A B L E XL VI 11 T E S T M AT ER IA L : A r o r l o r 1242 Tw o-Y ear Chronic Oral Toxicity Study - Albino Rats Description of Tum or Findings Group: Control Weight (grams) 11.76 64.98 35.09 - - - - 88.92 Size (cm) 8x1x2 5x2x2 - 2x2x1 2x2x3 - I 3 x 11 x 4 Classification Mammary fibroadenoma Adenocarcinoma Mammary fibroadenoma Mammary fibroadenoma Reticulum cell sarcoma Mammary fibroadenoma Mammary fibroadenoma Mammary fibroadenoma Mammary fibroadenoma 1'h c o c h r o m o c y Ionia Fibroadenoma _____ P % f1 c Months on T est 24 24 24 24 24 7 24 24 24 Forni38 00 > Animal Number and Sex 566 -M 569-M 604-F 609-F r 611-F s ** 613-F ^ C B is-f -/o--V Ul h Location Abdomen Spleen Abdomen Abdomen Abdomen Ovary Abdomen Abdomen ADM 0 0 3 7 1 5 T A B L E XLIX TEST MATERIAL: A ro c lo r 1242 Two-Year Chronic Oral Toxicity Study - Albino Rat Description of Tum or Findings Group: 1 ppm Weight (grama) 15.00 53.50 35.00 - 335.00 Size <c>" ) - - 5x3x1 5x3x1 Ixlxl 3x2x1 13 x 10 x 5 Classification Adenocarcinoma Lymphosarcoma Mammary fibroadenoma Fibroadenoma Fibroadenoma Fibroadenoma Granulosa cell tumor Fibroadenoma Mammary fibroadenoma Months on Test 24 22 24 4 24 24 23 : D C . n L i fvl Animal Number and Sex 621-F 627-F 62B-F 630-M *3rj63l-F 634-F Location Abdomen Pituitary Abdomen Abdomen Uterus Abdomen Abdomen Abdomen Pituitary AH 003 7 1 6 TABLE XLIX continued TEST MATERIAL: A ro c lo r 1242 Tw o-Year Chronic Ora! Toxicity Study - Albino Rats Description of Tumor Findings Group: 1 ppm oo* Weigh! (Kral" B> I B. 00 - 157.20 117.90 . 13.41 39. 36 - Size (cm) 1x3x3 - 6x3x3 9x6x4 7x6x2 3x2x 1 _ 6x5x3 6x5x4 - Classification Fibroadenoma Chromophobe adenoma Fibroadenoma Mammary fibroadenoma Mammary fibroadenoma Fibroma Fibroadenoma Fib roadenoma Fibroadenoma Chromophobe adenoma . Months on Test 24 24 24 23 24 24 24 J Animal Number and Sex 640-M 646. M 662-M 687- F 689-F 690-F 5 A05-F C c -F O Htn vo 1- F o Loo TABLE L TEST MATERIAL: A roclor 1242 T w o-Y ear Chronic Oral Toxicity Study - Albino Rats Description of Tumor Findings Group: 10 ppm Location Weight (grams) Abdomen Pancreas Adrenal gland Pituitary Abdomen 129.0 - 280. 0 Pituitary - Abdomen - Pituitary - Abdomen Abdomen 3.90 23. 15 Abdomen 175. 0 Parathyroid gland - Size (cm) 9x7x 3 - - - - - 3x 3x 2 7 x 6x 3 8x 7x 5 v C la ssifica tio n Fibroadenoma Islet cell adenoma Medullary tumor Chromophobe adenoma Mammary fibroadenoma Chromophobe adenoma Mammary adenocarcinoma Chromophobe adenoma Mammary fibroadenoma . Mammary fibroadenma Mammary fibroadenoma Adenoma Monllis on Test 24 24 24 22 24 24 24 24 24 24 O Or Animal Number and Sex 707- F 708- F 7H-F 7 12- F TA BLE L continue! TEST MATERIAL: A r o c lo r l2 4 2 T w o-Y ear Chronic Oral Toxicity Study - Albino Rats Description of Tumor Findings Group: 10 ppm Location Abdomen Abdomen ' Abdomen Subcutaneous, abdominal Weight (grama) 74.6 189.0 6. 96 155.0 Size (cm) 7x6x3 5x4x1 3x2x1 11x8x3 C la ssifica tio n Mammary fibroadenoma Mammary fibroadenoma Mammary fibroadenoma Fatty tissue fibroma Months on Test 24 24 24 24 . % ! c < n u i (fm uuj Ul to o ur> x O ou* iu r^ ' r o * Animal Number and Sex 744-M 775-F 7H5-F 7B9-F 794-F a T A B L E LI TEST MATERIAL: A roclor 1242 Two-Yea r Chronic Oral Toxicity Study - Albino Rats Description of Tumor Findi ngs Group: 100 ppm Location Panereaa Ovary Pituitary Adrenal gland Abdomen Weight (grama) 260.0 Size (cm) 10 x 10 x 5, C lassification Islet cell adenoma Granulosa cell tumor Chromophobe adenoma Medullary tuinor Mammary fibroadenoma * Months on T e at 24 24 24 24 23 i. r* ut -1 ni l/i --1 ? r oou uroi ct* > > I*V / M o n ssn to ;h T ' Nam oi Nomine Location _____ Pani L. Wright____________ _______________________________ Creve CsmsiA, Unii or Stall Olii- Oi.iMOn Bulinali CrouO Ooar|mn| Med. & Fnv. Hlth. Ponilo* Till Srliry ria Annual Salary Oaiaoi Lan inert Toxicolocv Manacer 19 Mrlornunc - S31,800 Crowin 2/1/76___ Data i_al ffloiap ( Typ Ol A m ite , (Sict tn iwi'fl cautery from in oppant wo el tnu mt ima moiiapprooriairiy flaicno*i in ra na mtf tn ci `csd 6lfl".| . Amit CJUSO'V Technical ^ Accomplishment og sionifleant results- _____________ lQfi. O atc/.o* in atA<*mant na Ui nn*fltnca io M o n u n to oalawn At a r ec en t m eeting in Creve Coeur, Glenn S c h w eitze r, head o f th e O ff T o x ic S u b sta n c es o f EPA, o f f e r e d some i n t e r e s t i n g comments. He o b ser' t h a t M on san to's t o x i c o l o g i s t s w ere h e ld in h ig h r eg a r d a t EPA. Howev< s i n c e i t la c k e d an in - h o u s e t o x i c o l o g y f a c i l i t y , Monsanto as a compan; n o t a s h ig h ly reg a rd ed o v e r a l l a s du P ont, C a r b id e , o r Dow. n( Dr. W righ t's p r o fe s sio n a l and p erson al c h a r a c te r is tic s have contribut n i f i c a n t l y to M on san to's image a t EPA. He has shown u n u su a l p e r sev e re and d e d ic a t io n , f r e q u e n t ly in v o lv in g h i s own tim e , to r e v ie w and in t e : la rg e volumes o f data which he su b seq u en tly organized fo r p r e se n ta tio i EPA o f f i c i a l s . P a r t i c u l a r l y n o tew o rth y w ers h i s e f f o r t s on p o ly c h lo r : b ip h e n y ls (A ro clo rs)- and c h lo r in a t e d is o c y a n u r a t e s (ACL p r o d u c t s ) . 1 1 former in s ta n c e , h is e x c e lle n t a n a ly s is and s y n th e s is o f w id ely s c a ttt o b s e r v a t io n s p la y e d a p rom in en t r o le in f o r e s t a l l i n g EPA*s p r o m u lg a te u n r e a lis tic r e g u la tio n s to lim it d isch arges of. p o ly ch lo rin a ted biphen; EPA's proposed r e g u la tio n s would have p reclu d ed th e use o f th e s e mate] by M onsanto's cu sto m ers. With r e sp e c t to c h lo r in a te d iso c y a n u r a te s, Dr. W right has had s e v e r a l c o n t a c t s w ith i n d iv id u a l s c i e n t i s t s a t EPA answer s p e c i f i c q u e s t io n s t h a t they had r a is e d o r to inform them o f tl s ta tu s o f a d d itio n a l stu d ie s which had been undertaken*. O v e r a ll, by v ir t u e o f th e q u a l i t i e s o f le a d e r s h ip w hich Dr. W right ha: p la y e d , he has made an im p o r ta n t c o n t r ib u t io n t o M onsanto's im age a t : That fa v o ra b le image w i l l become in c r e a s in g ly im portant to Monsanto, a a r e a s o f i n t e r a c t i o n w ith EPA m u lt ip ly . 1 0 0 1 1 A4 MONSANTO INDUSTRIAL CHEMICALS COMPARI FUNCTIONAL PRODUCTS GROUP STANDARD MANUFACTURING PROCESS for ROCLORS (Taka-over distilled) Department 246 Supercedes: Standard Manufacturing Process for Aroclors - Department 246, dated October 1966, and all amendments A through L. Tentative Process for the Continuous Manufacture of Aroclor 1242, dated 9/16/68, and designated Report No. P-1504. Prepared by: R. M. Me Cutchan Issued: January 1972 Approved General Manufacturing Superincenden Lu l iU U ^ *'W aearch'*. ^eveloment -Manager-" \ il f i c ^ o Manufacturing Manager >'*This procs* Is the property of Monsanto Industrial Qiemicals '-Company and the recipient is responsible for Its safekeeping. It contains confidential information of Monsanto Industrial Chemicals Company which must not be reproduced, revealed to unauthorized persons or sent outside the compare without proper "authorization. Either retain In a secure file or return to the Standard Documents Department. lorn 1 4 5 OOio DEPARTMENT 2 46 - ^STANDARD :IANITACTJ RING PROCESS aroclor APPENDIX J ft SAFETY AND TOXICITY DATA I . SAFETY EQUIP*-ENT A F ir e E x tin g u is h e r s . 1 . Carbon d io x id e - 1 s t f l o o r , NE o f le a n - t o 2 . Dry ch em ical - 1 s t f l o o r , SE o f le a n - t o 3 . Dry ch em ical - 2nd f l o o r , w est w a ll 4 Dry ch em ical - 2nd f l o o r , v e s t w a ll B * Gas M asks. 1 1 s t f l o o r , on s p r in k le r house 2 1 s t f l o o r , o u ts id e w est w a ll o f r e p a ir room 3 2nd f l o o r , on w est w a ll 4 . C ontrol room, e a st w a ll 5 . 4th f l o o r , on h a n d ra il by #1 c h lo r in a to r 6 . 4th p la tfo rm , A roclor column (2) Cm S c o t t A ir Pak. 1 O u tsid e w e st w a ll o f le a n - t o D. Emergency C lothin g. 1 . Box on 2nd f lo o r , w est w a ll. E. S a fe ty Showers v?ith Eye Nash. 1 B atch departm ent, 1 s t f l o o r , 2 B atch departm ent, 2nd f l o o r . 3 Batch departm ent, 3rd f lo o r . 4 C ontinuous departm ent, 1 s t f lo o r . : 5 C ontinuous departm ent, 2nd f l o o r . 4. C ontinuous departm ent, 3rd f l o o r . 7 . V e st s id e o f tank farm (alarm in c o n tr o l room) ^ t . C o n tr o l room (eye batch o n l y ) . F . p erso n a l S afety Eruitment A v a ila b le. 1 . Hard h a t. 2 S a fe ty g l a s s e s . 3 S a fe ty s h o e s . 4 . G oggles. 5 Rubber or canvai g lo v e s . 6 Rubber o v e r sh o e s. F n n ii4 6 124 aoh DEPARTMENT 246 . STAI!CARD !'A!:LTACT!;p.1:;g PROCESS AROCLOR (C on t'd ) APPENDIX J (C on t'd ) SAFETY AND TOXICITY DATA (C ont'd) I I . DEPART!S !T SAFETY RECORD (2 4 6 /2 5 9 ). A. L ost tim e a c cid e n ts - L ast occurred oh January 2 8f 1948 B. S e r io u s i n j u r i e s - 'The l a s t two s e r io u s in j u r ie s weret 1) 8 /5 /7 0 - See Attached inform al in v e s tig a tio n report 2) 1 2 /2 /6 8 - R efer to formal in v e s t ig a t io n rep ort L-17C. Minor i n j u r i e s . Year In ju r ie s No. o f Men 1969 1970 1971 12 12 13 20 20 24 III.TOXICITY The fo llo w in g to x ic r a tin g code w i l l be used in d escrib in g th e to x ic ity of these m aterials! 0 - none 1 - slig h t . i *- .-i *.-- J - n ig h U - unknown A. B ip h en y l (Code 82601) 1 Synonymsi ' D ip h en yl. 2 . D e sc r ip tio n i Khite fla k es or s o lid o f f white mass! somewhat p lea sa n t odor. 3 . C on sta n ts t Mol. Wt. 1 5 4 .2 | M.P. 6 9 #C .f B .P . 255*C.i te n s ity .9910 0 75*/4*C. 4 f l a s h P o in t : 235* F. (C .C .) 5 Auto I g n itio n Tem perature! 1004*F. 6 . Toxic hazard R atinei Acute Local! U Acute S y stem a tic! In g e s tio n 2t In h a la tio n 3 Chromic L ocali U 7 . F ir e H azard: D e f in it e ly when exposed to h ea t or f la r e j can react with oxid izin g m aterials. Zm F ir e F ig h t in g ! C02 or dry c h e m ic a l. <v 9 . Form ula I E S fsW iS f 1^7 125 ADM 00, SEFARTis:rr 246 - standard manufacturing process aroclor . APPENDIX J (C on t'd ) SAFETY AND TOXICITY DATA (C ont'd) III.(C on t'd ) A. (Cont'd) 10. B iphenyl vapors are ir r it a t in g to the upper resp iratory t r a c t . Workers should not be exposed to vapor le v e ls throughout th e ir s h if t in excess of the threshold lir .it value o f 1 m illigram per cubic meter o f a ir (or about 0 .2 ppm). The compound / or o r g a n ic s o lu tio n s o f th e com pound can absorb through the in ta c t skin; th erefo re, repeated skin contact should be avoided. 1 1. See H ygien ic Guide S e r ie s on "D iphenyl". B. C h lorin e (Code 81059). 1. D e sc r ip tio n t Greenish yellow gas. 2 . Formula: C l2 3 . C o n s ta n ts i Mol. K t. 70.914; !!.P.-101"C . ;B .P. - 34.5"C .; b e n s it y 1 .4 7 3 0#C. 4 . T oxic Hazard F a tin g ; Acute lo c a l: I r r ita n t 3; In h a la tio n 3 Acute system ic: 0 Chronic lo c a l: U Chronic system ic: U 5 . T o x ic o lo g y : C h lorin e i s extrem ely i r r i t a t i n g to th e mucou memoranes o f th e eyes and r e sp ir a to r y t r a c t . I t combines w ith m o istu r e to lib e r a t e n a sc e n t oxygen and from hydro- ' c h lo r ic -acid. Both o f th ese su b sta n ces, i f present in q u an tity, cause f in flam m ation o f the t i s s u e s w ith which th ey come in contac h I f th e lu n g t i s s u e s are a tta c k e d , pulmonary edema may r e st A c o n c e n tr a tio n o f 3 .5 ppm produces a d e te c ta b le Oder; 15 PPM c a u ses im m ediate i r r i t a t i o n o f the th r o a t. Con c e n t r a t io n s o f 50 PPM are dangerous fo r even sh o rt exposu: 1000 PPM may be f a t a l even when th e exposure i s b r i e f . Because o f it s in ten sely ir r ita tin g properties, severe i n d u s t r i a l exposure seldom o c c u r s , as the workman i s fo rced to leave the area before he can be se r io u sly a f f e c In ca ses where th is i s im p o ssib le, the i n i t i a l ir r it a t io n F/im 1 as 1 2 6 AC* CC DEPARTMENT 24 6 - STANDARD. MAJiLTACTUPJirG PROCESS AROCEOR APPENDIX J (C on t'd ) SAFETY AND TOXICITY DATA (Cont'd) I I I . 8< 5 (C ont'd) o f th e e y e s and mucous membranes o f th e nose and th r o a t i s fo llo w e d by cough, a f e e lin g o f s u ffo c a tio n and l a t e r pain and a fe e lin g c o n str ic tio n in the c h e st, i f exoosur has been s e v e r e , pulmonary edema may f o lio : / w ith r a le s being heard over the ch est. 6 . F ire Hazard; Moderate - can rea ct to cause fir e or e x p ic s io n - upon c o n ta c t w ith tu r p e n tin e , e th e r , aimronia g a s , illu m in a tin g g a s , hydrocarbons, hydrogen and powderm etals 7 E x p lo sio n Hazardi P resen t by r e a c tio n w ith red u cin g agen 8. P is a tte r Contro1 : Dangerous; em its h igh ly to x ic fumes; w i l l r e a c t w it., w ater to form t o x ic and c o r r o siv e fumes o f HCl; i s h e a v ie r than a ir - gas w i l l hug th e ground. P eop le w ith o u t adequate p r o te c tio n should go across wind u n til out of the a ffected area. C. HCl O ff-G as (Code 828.51) 1 Synonyms: M u riatic a c id , C h lorohyd ric A cid , Hydrogen Chic 2 . D escrip tion : C olorless gas. 3 . Form ula? KCl. 4 . T o x ic r.azard R ating; Acute lo c a l: Ir r ita n t 3, In g estio n 3, Inhalation 3 Acute System ics U Chronic lo c a l: Ir r ita n t 2 Chronic System ic: U 5 M .A .C .i 5 ppm in a ir fo r 8 h r . d a y . ' C t o x i c o l o g y : Hydrogen c h lo r id e i s an i r r i t a n t to the nucci membranes o f the e y e s and r e s p ir a to r y t r a c t . C on centratic o f 35 ppm ca u ses i r r i t a t i o n o f th e th r o a t a f t e r sh o rt expc C o n ce n tr a tio n s o f 50 t o . 100 ppm are t o le r a b le fo r 1 hour. More s e r io u s exp osu res r e s u lt in pulmonary edema and o fte n la r y n g e a l spasm. C on cen tration s o f 1000 to 2000 ppm are dangerous even fo r b r i e f e x p o su re s. M ists o f HCl are con sid ered le s s harmful than the anhydrous fora sin ce tne d r o p le t s have no d en yd ratin g e f f e c t . - 7* S ee H y g ien ic Guide S e r ie s on 'Hydrogen C h lorid e" . Io m 1 3 127 Aon C02t DIPART?TTTT 2 46 STANDARD MANUFACTURING PR0CIS5 AROCLOR APPENDIX J (C cn t'd ) SATEXV AND TOXICITY DATA (Cont'd) III . (Cont'd) D. F e r r ic C h lo rid e (Code 33500) 1. D e sc r ip tio n ; Granular s o lid . 2 . Form ula: r e C l3 (Annydrous) 3. C o n sta n ts; Mol. Iic t, 16 6 , 2 2 f M eltin g P t . s u b lir e s / s o l u b i l i t y in KyG * very s o lu b le v;ith h eat r i s e . 4. T oxic Hazard R a tin e; A cute L o ca l: I r r i t a n t 1? I n g e s tio n 1 Acute System ic: U Chronic Local: Ir r ita n t 1 Chronic System ic: U 5 . F ire Hazard; T.iere i s no f ir e hazard under normal condit but i t w i i i em it to x ic fumes a t high tem peratures. 6 . H a n d lin g : P r o te c t th e sh in v.*ith approved p r o t e c t iv e c lo t .iin g , avoid the breatning o f FeCl3 d u st, wear approve r e s p ir a t o r w ith adequate c a r t r id g e , and p r o te c t th e ey es w ith approved g o g g le s . There are no sto ra g e regu lation s'? however, i t should be stored in a dry p lace as heat i s r e le a s e d upon s o lu t io n in w ater and wet f e r r ic c h lo r id e w ill not catalyze the chlorination reaction . I . Lime (Code 38SOG) (Calcium Oxide) 1 . D e s c r ip tio n ; Fine w hite or s l i g h t l y gray powder, Rhomeri Trigonal c r y s ta ls 2 . Form ula; CaO. 3. Toxic hazard F atin g; Acute l o c a l ; I r r i t a n t 3; In g e s tio n 1? In h a la tio n 3. Acute S y stem ic: I n g e s tio n 2? In h a la tio n 3? sh in absorption 0. C hronic l o c a l : I r r it a n t 3? In h a la tio n 2. Chronic System ic: In g estio n 2; In h alation 3; Shin absorption 0. 4 T o x ico lo g y ; Has a c a u s t ic r e a c tio n and, th e r e f o r e , i s i r r i t a t i n g to ti shin. As a d u st i t can cause d e r m a titis and i r r i t a t i o n o f th e ey es and mucous membranes. I t i s a general nuisan type of dust. 5 . F ire Hazard: None. 6. Exolosicn hazard: V irtu ally none. 7 . Handling: Dust- r e sp ir a to r , adequate p ro tectiv e c lo th in g , in d u c in g rubber coated g lo v e s , o p tio n a l rubber f u l l cove; apron and f u l l cover p l a s t i c g o g g les should be used when r^ in n iU- 150 128 ADM 0C2fcl depart:-;*::;? 246 - standard manufacturing process AROCLOR APPENDIX J (C ont'd) SAFETY AND TOXICITY DATA (Cont'd) E. 7. (Cont'd) h an d lin g lim e (d u st)* Adequate v e n t i la t i o n and d u st remov equipment should be used in the handling area* Lime i s added to th e s t i l l s to n e u t r a liz e any lib e r a te d HC prevent sublim ation o f the FeCl3 c a ta ly s t, i t i s handled in 501 bags* F . N itro g e n (Coda 43099) 1* D e s c r ip t io n : C o lo r le s s gas 2* t o r n u l a s EiJ 3* C o n stan ts: Mol* Wt. 2 8 .0 2 ; M.P. - 210*C; B .P . - 1 9 5 ,8*C .| D en sity 1.2506 c r / l i t e r a t 0*C. 4 . T o x ic it y : None. In high c o n c e n tr a tio n s i t i s an ~ asphyxiant. G. A r o c lo r s . (See H ygien ic Guide S e r ie s on "C h lo r o d ip h e n y ls* ). iw m si ADM 002fc 129 ' I Monsanto MONSANTO INDUSTRIAL CNIMICALS CO. BOO N. LinODargh logl*vard St. Louit. Missouri 63165 ptona: OU; 984-1000 January 20, 1972 ) C f \j ^ Vestinghouse E le c tr ic Corp. Box loo=.ington, Indiana ^7^02 Gentlemen, As vc have p re v io u s ly n o tif ie d you by vay o f correspondence s ln e e a a rly 1970, Che a l t e r i s i d e s c r ib e d on th e s tts c h e d acknow ledgem ent o f your o r d e r c o n ta in s p o ly c h lo rin a te d b ip h e n y ls (PCB). P o ly c h lo rin a te d b ip h en y ls a re h ig h ly s ta b le e h e o ic s l compounds and arc not re a d ily b io d eg rad ab le, T h e re fo re , vhen placed in th e environm ent they aay be considered con ta m in a n ts and a a y a d v e r s e ly a f f e c t some s p e c ie s o f a n im a l and n a r lo e l i f e . You m ust ta k e ev ery p r e c a u tio n to p re v e n t any e n try o f p o ly c h lo rin a te d biphenyls In to the environm ent through s p ills , uaage, leakage, d isp o sa l, vapo rizatio n or otherw ise. T h is m a t e r i a l sh o u ld n o t be used by you or* y o u ^ custom er in equipm ent, packaging m a te ria ls o r products involved in the p ro cessing, handling, or sto ra g e o f food, food re la te d p ro d u cts, anim al feed s, food wrapping or co n tain er m a te ria ls, p otable w aters or pharm aceuticals. Very tru ly y o u rs, Howard S. B erg en , J r ^ * D irector S p e c ia lty P roducts Croup /jf unit of M enii" Comertf (Typed from Original) January 15, 1972 Monsanto Industrial Chemicals Co. 800 N. Lindbergh Boulevard St. Louis, Missouri 63166 Gentlemen: Monsanto Company ("Monsanto") m anufactures certain polychlorinated biphenyl products CPCB*s") which Westinghouse Electric Corporation ("Buyer") desires to purchase. While Buyer desires to purchase FOB'S because o f certain desirable flame resistant and insulator properties, Buyer acknowledges that it is aware and has been advised by Monsanto th at FCB^s tend to persist in the environment; th at care is required in their handling, possession, use and disposition; th at tolerance limits have been or are being established for PCB^ in various food products. Monsanto has therefore adopted certain restrictive policies with respect to its further production, sale and delivery of PCB^s, including the receipt o f undertakings from its customers as set forth below, and Buyer is willing to agree to such undertakings with respect to sales and/or deliveries of PCB's by Monsanto to Buyer. Accordingly, Buyer hereby covenants and agrees th at, with respect to any and aQ PCBV sold o r delivered by or on behalf of Monsanto to o r for the account o f Buyer on or a fte r t h t j i t e hereof, and In consideration of any such sale or f, Buyer shall defend, indemnify and hold harmless to, its present, past and future directors, officers, and agents, from and against any and all liabilities, claim s, damages, penalties, actions, suits, losses, costs and expenses arising out of or a connection with the receipt; purchase, possesion, handling, use, sale or d i^o sitio n of Fjftflt153 Monsanto Industrial Chemicals Co. Page Two January IS, 1972 such PCB*s by, through or under Buyer, whether alone or in com bination with other substances, including, without implied lim itation, any contamination of or adverse effect on humans, marine and wildlife, food, animal feed or the environment by reason of such PCB^ The point a t and a fte r which the provisions of this agreem ent shall apply to PCB^s sold or delivered by or on behalf of Monsanto to or for the account of Buyer on or a fte r the d a te hereof, and the point a t which title and risk of loss with resp ect to such PCB^s^tall pass from Monsanto to Buyer, shall be the F.O.B. point at the location from which delivery to Buyer is initiated by Monsanto, and shall refer to the point of tran sfer of possession of the drum, tank car, tank truck, or o th e r container for such PCB*s, from Monsanto to Buyer or the first receiving carrier utilized to effect delivery of such PCB*s to Buyer. The provisions of this agreement shall not be applicable to any PCB*s delivered to Buyer prior to the date hereof; and nothing herein shall c re a te or imply any duty or obligation: (i) of Monsanto to sell or deliver any PCB1* to Buyer; or (ii) of Buyer to defend, indemnify or hold harmless Monsanto or any other corporation, dr any person, for any damages resulting from the negligence o f Monsanto (in the absence of negligence o f Buyer) in Its packaging or shipping of PCB^s or from th e failure of PCB^s to comply with the contract specificaUjOQS applicable to such PCB^s. No conditions, understandings o t j i f t e m e n t s purporting to modify or vary the term s hereof a t U K ^ b M i n g unless hereafter made In writing specifically refSm tiig to this agreement and signed by the party to be bound and no modification or variance of this agreement shall be e ffe c te d by the acknowledgment or acceptance of any sale document, purchase order, shipping instruction or other forms containing term s or conditions at variance herewith. F o r n ix Monsanto Industrial Chemicals Co. Page Two January 15, 1972 In the event of litigation to which these indemnity provisions shall apply, Monsanto "U make available to Buyer such information as Monsanto has (excluding trade secrets or proprietary information of Monsanto, or any other information which Monsanto is not legally free to disclose) which may reasonably t>e required by Buyer in the defense of such litigation, and otherw ise will cooperate with Buyer in connection therewith. This agreement shall be governed by and be construed according to the laws of the State of Missouri. All existing contracts for the sale of PCB's by Monsanto to Buyer for delivery in the future are hereby amended to contain the provisions set forth herein. WESTINGHOUSE ELECTRIC CORPORATION By (Signature)_____________________ Title Vice President______ Date January IS, 1972_______________ MONSA NTO COM PANY ORIGINAL SIGNED BY: B y_______ E. J. Ptitzell______ 1001155 Monsanto MONSANTO INDUSTRIAL CHEMICALS CO. BOO N. LindarQh Boulevard \ St. Louii, Mitaouri 63166 Phon; 1314) 694-1000 4. January 20, 1972 Westinghouse E le c tr ic Corp. Box 3^-1 Bloocington, Indiana ^7^-02 Gentlemen, Aa v e h av e p r e v io u s ly n o t i f i e d you by way o f c o rre sp o n d e n c e s in c e e a r l y 1970t th e m a te ria l d escrib ed on th e atta ch e d acknovlodgement of your order c o n ta in s p o ly c h lo r in a te d b ip h e n y ls (PCB) P o ly c h lo r in a te d b ip h e n y ls a r e h ig h ly s ta b le chem ical compounds and a re not r e a d ily b io d eg rad ab le. T h e r e f o r e , vhen p la c e d i n th e en v iro n m en t th e y may b e c o n s id e re d con ta m in a n ts and may a d v e r s e ly a f f e c t some s p e c ie s o f a n im a l and m arin e l i f e . You m ust ta k e ev ery p re c a u tio n to p re v e n t any e n try o f p o ly c h lo rin a te d biphenyls In to th e environment through s p i l l s , usage, leakage, d isp o sa l, v ap o risatio n or otherw ise. This m a te ria l should not be used by you o r your custom er In equipm ent, packaging m a te ria ls or products Involved in the pro cessin g , handling, or sto rag e of food, food re la te d p ro d u cts, anim al feed s, food wrapping or container m ate ria ls, potable w aters or pharm aceuticals. Very tr u ly yours nt A ttachm ent Howard S. B ergen, S t y D irector S p e c ia lty P roducts Group unit of Monsanto Cotnsanv Foni 156 100590 Monsanto MONSANTO INDUSTRIAL CHEMICALS CO. . 800 N. Lindbergh Oouieverd Si. Louis, Miicowri 63166 Phon: 0141 664-1000 'SPECIAL UNDERTAKING 3Y PURCHASERS OF POLYCHLORINATED BIPHENYLS M onsan to Company ("M onsanto") m a n u factu res c e r ta in p o ly c h lo r in a t e d b ip h e n y l p ro d u cts ("PCB's") w h ich G eneral E l e c t r i c Company ("Buyer") d e s ir e s to p u r c h a se . W hile B u yer d e s i r e s t o p u rch a se PCB's b e c a u se o f c e r ta in d e s ir a b le flam e r e s is t a n t and in su la to r p r o p e r tie s, Euyer a ck n o w led g es t h a t i t is aware and h as b een a d v ise d by M onsanto t h a t PCB's ten d to p e r s is t in th e environm ent; th a t ca re i s req u ired in th e ir h an d lin g, p o sse ssio n , use and d is p o s itio n ; th a t to lera n ce lim its have been or are b e in g e s t a b l i s h e d f o r PCB's in v a r io u s fo o d p r o d u c ts . M onsanto has th e r e fo r e adopted c e r ta in r e s t r ic t iv e p o lic ie s with- r e s p e c t t o i t s fu r th e r p ro d u ctio n , s a le and d e liv e r y o f P C B 's, in c lu d in g th e r e c e ip t o f u n d e r ta k in g s from i t s cu sto m ers a s s e t fo r th b elow , and Buyer i s w illin g to a g ree to such' u n d erta k in g s w ith resp ect to s a le s and/or d e liv e r ie s o f PCB's by M onsanto to B uyer. A c c o r d in g ly , B uyer h ereb y covenants and a g r ee s th a t, w ith r e s p e c t t o any and a l l PCB's s o ld or d e liv e r e d by o r on b e h a lf o f M onsanto to Buyer on or a fte r th e d a te h ereo f and in c o n s id e r a tio n o f any such s a le or d e liv e r y , Buyer s h a l l d e fe n d , in d em n ify and h old h arm less M onsanto, i t s p r e se n t p a s t and fu tu r e d ir e c t o r s , o f f i c e r s , em ployes and a g e n t s , from and a g a in s t any and a l l l i a b i l i t i e s , c la im s, dam ages, p e n a l t i e s , a c tio n s , s u i t s , l o s s e s , c o s ts and e x p en ses a r is in g o u t o f or in con n ection w ith the r e c e ip t, p u rch ase, p o sse ssio n , han d lin g, u se, s a le or d isp o sitio n o f su ch PC B's b y , th rou gh or under B uyer, w h eth er alon e or in co m b in a tio n w ith o th e r substances,* in c lu d in g , w ith o u t im p lied l im i t a t io n , any co n ta m in a tio n o f or a d v erse e f f e c t on humans, m arin e and w i l d l i f e , food, anim al feed or th e environm ent by rea so n o f such PC B 's. -2- A l l e x i s t i n g c o n t r a c t s f o r th e s a l e o f PCB's by Monsanto to Buyer a re h ereb y amended to contain th p ro v isio n s s e t forth above. N othing h e re in s h a ll c re a te or imply any duty o r o b lig a tio n o f M o n s a n t o t o s e l l o r d e l i v e r a n y P C B 's t o B u y e r . No c o n d i tio n s , u n d e rstan d in g s or agreem ents p u rp o rtin g to modify o r v a r y th e term s h e r e o f s h a l l be b in d in g u n le s s h e r e a f t e r made in w ritin g s p e c ific a lly re fe rrin g to th is agreem ent and s ig n e d by th e p a r t y to b e bound and no m o d ific a tio n o r v arian ce of the above undertaking sh a ll be e ffe cte d by the acknowledgment or acceptance of any sa le document, purchase o rd e r, sh ip p in g in s tr u c tio n or o th e r forms c o n ta in in g term s o r co n d itio n s a t variance herewith* G EN ER A L ELEC TR IC CO. MONSANTO COMPANY TITLE j V ice P re sid e n t and C orporate Counsel DATE: Ja n u a ry 21. 1972 jijn n il& B IDS QC Monsanto MONSANTO iNOUSTftlAL CHlMtCALS CO. 800 N. LinO.rgh Boulevard St Lauti. Mutoufi 83186 Phon: ;3U) 894-1000 February 4, I972 Dear Sir: We are writing to advise you that Monsanto has adopted certain policies with respect to its further sale and delivery of all polychlorinated biphenyl (PCB) products used as dielectric fluids includlngjput not H a l t e d to those sold under tradensaes such as Aroclor'3?J InerteenS^ and PyranolS^ and under the generic texm askarel. Effective Immediately Monsanto will sell and deliver these prod ucts only to manufacturers of electrical equipment or components who utilize the products as dielectric fluids and who have entered Into agreement to Indemnify and hold harmless Monsanto In the use of these products. The two copies of such an agreement are at tached. The acceptance by Monsanto of such an agreement Is sub ject to receipt of financial and other Information from you (such as evidence of adequate Insurance protection) which, In Monsanto's opinion, makes the agreement meaningful. As you are undoubtedly aware, .studies Indicate FCBs may be accumu lating In the environment. In some Instances, FCBs have been found In food or in the food chain. For your Information, attached is an article by Carl G. Gustafson of the Pederal Water Quality Administration appearing in "Environmental Science & Technology" whlefc deals with this subject. Because of Monsanto's concern over thle problem, we have discontinued sales of FCBs except for use as dieXemtric fluids In electrical equipment and components. If you desire to continue purchase of these products from Monsanto, please have the attached copies of agreement signed by an authorized officer on behalf of your company and forward a fully signed copy, together with your most recent audited financial statement and any other Information which you feel will assist Monsanto In its evalua tion. F n n ii5 9 22 ACM 002* Page 2 If you Itavt any questiona please telephone (314) 694*2455 or write directly to Mr* H.S. Bergen, Monsanto Company, p.o. Box 14617, St. Louis I Missouri 63178. We sincerely regret any hardships that this decision may cause you hut it is taken in an effort to continue to make available these products for these important electrical applications. Very truly'yours /hi Enclosures Howard Bergen, Director Specialty Products Oroup Monsanto Industrial Chemicals Co V0011GO Monsanto MONSANTO INDUSTRIAL CHEMICALS CO. 800 N. Lindbergh Boulevard St. Louis, Missouri 63109 Phone: 014) 684-1000 February 17, 1972 I We a r e w r i t i n g t o a d v is e you t h a t M onsanto h a s ad op ted c e r t a in p o l i c i e s w ith r e sp e c t to th e fu rth er s a le and d e liv e r y o f a l l p o ly ch lo rin a ted b ip h e n y l (PCB's) produ cts in c lu d in g th o se so ld under tradenames such as Aroc lo r , In er tee n , P yran ol() , and under the g e n e r ic term ask arel. S t u d ie s have in d ic a t e d PCB's may b e a ccu m u la tin g in th e en v iro n m en t. In some in s ta n c e s PCB's have been found in food or in th e food c h a in . B ecau se o f M onsan to's concern o v er t h i s problem we have d is c o n tin u e d s a le s o f PCB's in a l l a p p lic a tio n s e x c e p t as d i e l e c t r i c f lu id s fo r u se in tra n sfo rm ers, c a p a c ito r s , and o th er e l e c t r i c a l equipment and com p onents. In the p a s t, Monsanto has so ld th e se f lu id s d ir e c t to transform er component m anufacturers and a ls o to makers o f in s u la tio n such as K raft paper and p l a s t i c f ilm who u se o n ly sm a ll amounts o f th e d i e l e c t r i c flu id fo r t e s t in g p u rp oses. Monsanto has decided to d isco n tin u e such d ir e c t s a le s . For your futu re requirem ents o f th ese d ie le c tr ic flu id s , we su g g e st you c o n ta c t th e A ro clo r c a p a c ito r m akers, or in the ca se o f transform ers c o n ta c t th e makers o f th e a sk a rel ty p e s. We s i n c e r e l y r e g r e t any in c o n v e n ie n c e t h i s d e c is io n may ca u se y o u . I f you have any q u estio n s r e la t iv e to t h is d e c isio n p le a se teleph one (314) 6 9 4 -2 5 1 3 , o r w r it e d i r e c t l y t o Mr. P au l B e n ig n u s, Monsanto Company, P . O. Box 14617, S t . L o u is, M isso u ri 63178. T. L. G ossage/ M arketing D irector S p e c ia lt y P rod ucts Group /jf unit of Monsanto Company F.O M IS I A0M 002**9 Monsanto MONSANTO INDUSTRIAL CHSM CAU CO. 800 N. Lindbergh Boulevard St. Louis, Missouri 63188 Phon: 3U) 884-1000 February 28, I972 Attention: Plant Engineer Dear Sir: Ve are writing to advlae you that Monsanto has adopted certain policies with respect to the further sale and delivery of all polychlorinated biphenyl (PCBs) products Including t h o s e a o l d under tradenames such as Aroclor O j Inerteen Pyranol CS4 and under the generic term askarel. Studies have indicated PCBs may be accumulating In the environ ment. In some Instances PCBs have been found In food or In the food chain Because of Monsanto's concern over this problem, we have discontinued sales of PCBs in all applications except as dielectric fluids for use In transformers, capacitors, and other electrical equipment and components. In the past, Monsanto has sold these fluids direct to transformer repair shops and to any one requiring the fluid for top-up of an existing transformer. Monsanto has decided to discontinue direct sales to transformer repair shops and for transformer top-up. For your future require ments of dielectric fluids, we suggest you contact the manufacturer of the transformer for which you desire the fluid. We sincerely regret any hardships that this decision may cause you, but It has been taken in an effort to continue to make available these products for Important electrical applications. If you have any questions relative to this decision, please telephone (314) 694-2513* or write directly to Mr. Paul Benlgnus, Monsanto Company, P. 0. Box l*6l7, St. Louis, Missouri 63178. Very truly yours, Al cc: Purchasing Agent t . LKJsuge Marketing Director Specialty Products *001162 r^ u n n in g h a m Papageorge if March 3, 1972 Hr. Paul DePalco Jr. Regional Administrator U.S. environmental Protection Agency Region XX 100 California Street San Pranclsco# California 94111 Dear Mr. DePalcoi X have been ashed to respond to your letter addressed to Mr. 8. J. Bock, asking for certain information regarding sales of polychlorinated biphenyls by Monsanto and Central Solvents and Chemicals in the Los Angeles County area. X know that you have dis cussed this by telephone with Mr. V. B. Papageorge and X have reviewed the situation with him. the names of our customers- rot the products W m a k e , w " nor the quantities of products these customers , purchase. We consider this to be proprietary informa tion and therefore hold it confidential. Consequently we do not feel free to comply with your request for data on customer names and quantities purchased. O a the other hand, last Hcveniber we did release to governmental agencies, including the SPA, Monsanto's total production and sales figures on PCS'* for the years 1960 through 1911. These statistics have been released publicly and earlier this year we discussed them in detail with members of the scientific 1 4 1 ADM 0 0 6 L Mr; Paul DeFalco# Jr. March 197*2 Pag 2 ; ccaajinity mod with representatives of tha Washington *ltl-agency PCB task force of which EPA ia a menber. for your reedy reference I axa encloeing a copy of this infonnatioo. Wa carta inly ahara your conearn and desire to control tha discharge of PCS'* Into tha environment. it is because of this concern that wa Implemented a program of self-imposed curtailment of sales of these products so that now wa are only offering continuing supplies for closed system dielectric applications where tha potential danger of environmental contamination ia carefully controlled. Furthermore# as another step in safeguarding tha environment we have Informed all customers of PCS materials of the potential .dangers should these materials escape and have strongly urged them to take every precaution to prevent loeses through spills# usage# leakage# disposal# vaporisation or otherwise. Z regret we cannot comply with your request for customsr Information but If we can be of assistance to ycu In other ways we will be glad to visit you or yoir designees to discuss the PCB situation further. .. *r.~-' --* t -'a *r Sincerely# V. R. Corey# Director Functional Product Groups /j* Enclosure ccs Hr. Charles H. Socamer/Monaanto 1001184 142 *0* OGo i MITSUBISHI MONSANTO CHEMICAL COMPANY POMLOG*POM ---------- :------------------j Tokyo t' pcb in JAPAN -------------- . . - - * I *." ircKInes** t ' "m _l ' - _- ~ V f *7*' * V.!.." Y r:- ` .ri. ; ' ' . O- - ? ' v k ' V ' -' - i: TO j . s Mr. P. G / b e n i g n u s .-- : '' S t (.BL2Soj/)fs* -* Marsh "* ; ch a rd _/ - S t . unch - ?i Papageorge- ; ; Coleman T'Kewi Dear Paul:' - I am p le a s e d t o a n sw er y o u r q u e s t i o n s In you r l e t t e r o f March 2 0 , 1 9 7 2 .- - ./ . 9 T h e-M in istry o f In ter n a t io n a l T rade-and-Industry.-(M ITI 1 *- i s s u e d n o t i c e y e s t e r d a y - t o a lm o s t * e v e r y i n d u s t r i a l * i : a s s o c ia tio n co n cern ed , as sum m arized^in the fo llo w in g : a-. N o - e l e c t r i c a l m a ch in e ry and eq uip m en t w h ic h z . c o n ta in " PC-B m u st be m a n u f a c t u r e d - a f t e r Sepr*' 1", ""1 9 7 2 . T b.- No' h e a t e x c h a n g e equi-pment- must--be -p r o d u c e d -- - a f t e r - J u l y 1 ,' .1972 w h ich u s e PCB* a s a .- t r a n s f e r . *.* . :*- m edium . . - ^ c . E xceptions- to the above are those-w hich a r e - .* s o l d t o th e s p e c i f i c `u s e r s and w h ich c a n b e - - . 1- r e t u r n e d - * a f t e r -u se ^ to .th e = produ cers-;orw manu^... i-* . f a c t u r e r s . - f or :PCB`" d is p o s a l.; They must?" r p e r i o d i c a l l y r e p o r t - t o th e ^ m in is tr y - how PCB--" is u sed ," shipped, s to r e d r e c o v e r e d , retu rn ed * and d is p o s e d ,- in c lu d in g m achineryy in a d d itio n , .../ t o - t h e q u a n t it y , d e a lt'r w ith -and s o -and s o f o r t h * *Everyl. u s e r - o f " PCB-c'onta in in g machi-ner.y-and?-^.*-- - equipm ent.-w il-lV T iave ^to b e -r e c o r d e d -a n d --r e g is te in t h e o f f i c i a l "l i s t ' t o - i n s u r e s t r i c t s u p e r .v is ' in the -fu tu re. d. Import o f su ch m achinery and.equipm ent w ill be p o s s ib le -o n ly --if- p e r m is s io n -is gran ted by -the G overnm ent^- a f t e r ' S e p t e m b e r - 1 , 1972V ' *i . e.-PCB c o n ta in in g -m a c h in e ry and equipment a lre a d y in u se must be id e n t if ie d and-reported to the. a u t h o r i t i e s s o t h a t th e d i s p o s a l o f PCB i s t o be made c o m p le te ..- F,0011:65 : lOp-2 w*vr, r You will understand that the above action is not the' total-' ban of PCB usr.ge. However, who can meet such stringent regulatory requirements to continue'using PCB, other than * non-civil organisations?^ -j. . i \4 ' . y% L, Ve called the MITI yesterday to learn the following: .*.? * *' t 1. The MITI foresee by the action taken yesterday the *' use of PCB fluid will be limited in the near future *' to the transformers used by-the Japan National. Hailroad and certain electronic parts in missiles belonging to the Defense Ministry,-, in addition to ' the high voltage electro-furnace capacitors as a possibility. 2. Thermal transfer systems with PCB will sooner or later undergo change in fluid or-the whole line will have to discontinue operation. 3. Kaneka agreed to follow the recommendation by the MITI to discontinue the production-of PCB, probably after September of this year. 4. Those who are able and obliged to use -PCB will have - l to import PCB, possibly from Bayer,^with permission from the Government. v You rightly pointed out that the actions being taken by the Japanese Government appear out of line from the rest of the world today.- I can agree*-to Mr. Terasaki's statement .. in this respect that the folks go all the way when they decide to do something in^this country.. I -think?-the latest- happening- sensationa-l-ly' moved the--. Government-' to-^his -direction - the analysis ..of.mothers milk in Osaka showed PCB level of 0.7_to 0.1 PPM, as against the PDA's 0.2 maximum level'for-cows milk.^ In. the Diet commit tee the Welfare Minister-was .at- a loss when -asked if-or not babies .can- drink /.mi-llC-wi-th--0 r7 PPM'-PCB. without a n y -- danger "to their healthy growth. You might recall Yodo River flows from lake Biwa to Osaka. B a y . Two capacitor plants are-located by.jthe* Lake-Nichicon 's a n d Nisshin Electric's'. Samples of the. soil' were taken from the vicinity-of Nichicon^to run analysis of PCB with an*- .- unfortunate result showing. 1,000 PPM PCB!*: ' - `r ' ' . .' O/ : Fnniifi6 '1 0 0 0 2 8 People associated the contamination of 'the'soil with the mothers* milk case. Thus Nichicon was forced to announce , last week that they plan'to discontinue production of PCB capacitors, after coining September. p 4 , Today the world seems to be ruled by feeling and not rason. The pressure against PCB usage is far from logical. It is quite emotional and-at the same time political, It was this pressure that led Kaneka to the discontinuation. It has not been 100% confirmed but I think you may rest ' assured Kaneka will not go after overseas markets after the fall of this year, although they are exporting substantially today. The grand funeral of PCB in Japan is close at hand. What .will replace PCB -in the dielectric, markets is yet known to nobody exactly.' We only are aware a number of products ranging from silicone to polyisobutane, wax.and DOP are competing. The strongest candidate on .the -longer term basis seems 'to^ me entirely new systems after technological..' innovation. - T wish you good luck.* TK/ym T. Katayama - P.S.-Just before. I had-thi-s-letter typed, Kaneka. announced . that the'y decided to disconiinue-the production of--Kaneclor-by'.the. end of-June,TM which-was-confirmed by . * myself today.with Kaneka. Also Nichikon was forced" to terminate their production of*PCB capacitors at the end.of-April. ionttf.7 1 0 0 0 2 !) Monsanto MONSANTO tNOUSTNlAl CMSMlCAU CO. MO M Cindlorgit loultvtf St Lom>. Ulf tourt 93166 **ant Oui 664-1000 April, 1972 Dear Sir: Since early 1970 we have been advising your company of signifi cane developments relating to the polychlorinated biphenyl (PCS) environmental situation. As you know, many pollution control agencies conduct monitoring programs to evaluate the presence and Impact of many materials on the environment. Some of these programs include PCB. Recently a representative of a governmental pollution control agency contacted Monsanto requesting information concerning PCB sales. Specifically, he asked for names and addresses of ?C3 customers in his area, with the quantities of PCB product sold to each. He stated chat this information was being re* quested because significant amounts of PCB were being detected in the discharge from sewage treatment facilities in his area. He was informed that Monsanto considers information of this type confidential and, therefore, does not disclose it outside the Company. He subsequently informed us that the request for information was being sent to the local federal district attorney for appropriate.action. As wt-.hgve pointed out on numerous occasions to representatives of g o v e M M n t and of private groups, Monsanto has long had a policy ..which it continues to follow, of treating information concerning its customers as confidential information. However, you should be ewere that, because of governmental or judicial orders or requirements or because of a change in circumstances resulting from the unique nature of the PCS problem, Monsanto may et tome future date be obligated to disclose such informa tion to qualified peraone. r Knniisa V w uml of Montoni Comi*V A O * O02"' 9 We wish to strongly re-emphasize with you the Importance or avoiding direct or accidental PCB contamination of feed, food and packaging material and of preventing PCS'a from escaping into the environment, we direct your attention to the recent FDA notice of proposed rule making on PCS's published in the Federal Register# Vol. 37, No. 5^# PP 5705 and following, dated March 13, 1972. If PCB's are still present at your locations you are urged to thoroughly review your procedures and inspect your facilities to insure that extreme care is taken in the handling, use, storage, and disposal of these materials. Sincerely, W. a. rapageorge Manager Environmental Protection K n n ii 9 C AO* 00i<tS PRESENTATION To The INTERDEPARTMENTAL TASK FORCE ON PCBa WASHINGTON, D. C. 1 ! May 15, 1972 by i MONSANTO COMPANY 1 ] 3 1 Fonino ^ ADM O222 Introduction Si V. B, Paoageorge * C o n sid e ra b le i n t e r e s t h as b e e n c o n t i n u e s to be expressed by many i n v o l v e d i n s t u d i e s of FCBSliftid t h e 4bvlronrr.ent c o n c e r n i n g t h e i r d e g r a d a b i l i t y . Monsanto riSjg rec^veji many i n q u i r i e s r e l a t i n g t o r e s u l t s o f o u r s t u d i e s . We nove h a v e t a c c u m u l a t e d seme m e a n i n g f u l d a t a w h ich we b e l i e v e would b e a p p r o p r i a A * t o p r e s e n t i n a s t a t u s r e p o r t t o t h e I n t e r d e p a r t m e n t a l PC3 T a s k F o r c e . We s i n c e r e l y ap p reciate th is opportunity to share th is inform ation with you this afternoon. S l i d e #1 - We p l a n t o d i s c u s s c u r r e n t r e s u l t s o f l a b o r a t o r y b i o d e g r a t i o n s t u d i e s o f FC3s a nd t h e l e v e l s o f PCB r e s i d u e s observed in the tis s u e s o f lab o ra to ry animals which were used i n o u r t o x i c i t y s t u d i e s . We w i l l r e v i e w b r i e f l y a c t i o n s M on santo h a s t a k e n t o r e d u c e PCB u s a g e a n d e n v i r o n m e n t a l l o s s e s . We w i l l also discuss the app licatio n of our laboratory findings to the d e v e l o p m e n t o f a m o d i f i e d more r e a d i l y d e g r a d a b l e PCB m i x t u r e f o r u s e by' t h e c a p a c i t o r i n d u s t r y a s a d i e l e c t r i c f l u i d . - As many o f you a r e a w a r e , we h a v e d e s i g n a t e d t h i s m a t e r i a l a s A r o c l o r 10 16 . S lid e yg - Our p r e s e n ta tio n w i l l begin with Dr. Tucker d iscu ssin g p r i m a r y , b a c t e r i a l d e g r a d a t i o n a n d FCB r e s i d u e s i n f i s h , fo w l a nd m a m m a l " t i s s u e s . D r. Munch w i l l r e v i e w e v i d e n c e t h a t d e m o n s t r a t e s d i s a p p e a r a n c e o f FCBs fro m t h e e n v i r o n m e n t a n d D r . P a t o n w i l l d i s c u s s M o n s a n t o 1s PCB s a l e s a n d u s e a c t i o n s a n d t h e I m p a c t t h e s e a c tio n s w ill have on the environment. B e c a u s e o f . t h e l i m i t e d t i m e a v a i l a b l e , may I s u g g e s t t h a t q u e s t i o n s be held u n t i l a l l the speakers have completed t h e i r re p o rts . Following the p re s e n ta tio n s th ere w ill be o p p o rtu n ity fo r f u rth e r d i s c u s s i o n o f i n f o r m a t i o n which may b e o f p a r t i c u l a r i n t e r e s t t o you. D r. T u c k e r , R e s e a r c h Group L e a d e r , w i l l now p r e s e n t a s t a t u s report of his laboratory resu lts. 1001171 0CQ2*3 OBJECTIVES O PROGRESS REPORT ON LABORATORY BIODEGRADATION OF PCB'S O RESIDUE 149334.87....... STUDIES IN FISH, BIRDS AMD MAMMALS O TO SHOW REDUCTION IN LESS BIODEGRADABLE PCB'S AS A RESULT OF MONSANTO ACTIONS ON SALES AND PRODUCTS Yl l w u i ADM 000225 i O INTRODUCTION AGENDA VI. B. PAPA6E0RGE O.PCB STUDIES PRIMARY BACTERIAL DEGRADATION RESIDUES IN FISH/ FOWL AND MAMMALS E. S. TUCKER o' EVIDENCE FOR LOSS OF PCB FROM THE ENVIRONMENT R. H. MUNCH O MONSANTO PCB ACTIONS C. PATON O DISCUSSION 1 'ASS2SSJ!SN,r o ^ T H 3 ' 3I0LCGICAL. FEHSlSTSSr POLYCHLORli.~AT3D 3IPH3NYLS By Dr. E. S. Tucker The research-I will review today will foce;; ur*nn one aspo.c t o f r'o.i- santo's efforts to understand t.m-: envircni^ivLcil impact of our polychlorinated biphenyl or veil products. * knd " ** b eh av io r V This research was initiated early in I960 after development of the necessary PC3 analytical methodology and subsequent confirmation of Dr. Soren Jensen1s identification of PCS residues in fish and'birds in Sweden. . * At this point in time, PCB residue data from Monsanto and external environmental monitoring programs indicated that at the previous rate of use and release of these products that same PCB homologs were beginning to reach detectable levels in fish, birds and mammals. Conversely, these data indicated to us that with the exception of localized, controllable contamination, PCB homologs with loss than five chlorine atoms per molecule had not accumulated to detectable levels; even though it was known that significantly greater amounts of the PCB homologs with less than 5 chlorine atoms per molecule had been manufactured and used over the years. Now, before discussing our biological studies, I would like to review for you the gross homoleg composition of our Aroclor products " and then in a very brief fashion, try and illustrate to you the complexity of these materials and hence the complexity of the problem. In the first slide (#1) , is shown the most recent data on the weight compositio'n of four of our Aroclor products as a function of each detectable PCB homolog. The first column on the left lists the homolog in question and the subsequent columns under each product show the weight distribution of each PCB homolog in each product. As most of you probably knov;, with the exception of Aroclor 1016, the last two digits of each product number refer to the degree of chlor ination. For example, Aroclor 1221 contains 21% chlorine by weight, and so on. Aroclor 1016 is a special case in that v/hiJ e it contains about 41% chlorine by weight, its penta, hexa, and haptachloro biphenyl content has been significantly reduced with respect to Aroclor 1242, a product produced by direct chlorination, containing 423 by weight chlorine. Please note that .the penta, hexa, and heptachloro biphenyl honologs in Aroclor 1016 have been reduced by factors of about 3, 10, and 10, respectively, with reference to Axoclor 1242. As you can also see, the chief constituents of Aroclor 1221 are the mono- and dichloro biphenyls, while Aroclor 101(1 aiyl Aronlor 174 2 contain predominantly d.i-, tri-, and tetrachloro biphenyls, and Aroclor 1254, tetra, penta, and hexanhloro biphenyls. *QM 00 02 26 ! n w i i t a n d ' a s s u c h -* - m ta lie s F o ^ y e ^ w a y h a v o . s e e n e n t i m a t i o n * ? o& th W h a s S s in " c o n te n t o f tliesc. products, which a re s ig n i f ic a n t l y differen t." T h - ^ a n a ly tic a l methodology used i s c u rre n tly in a very dynamic s ta te and our understanding o f th e c o n te n ts of th ese products in creases a^ t h e . m e t h o d o l o g y i s i m p r o v e d . A t t h i s p o i n t i n ' t i m e , we r e g a r d 'u v ^ sc numbers as the most acc u ra te ones c u rre n tly a v a ila b le . In the next slide (S2) are shown examples of low resolution - packed column electron capture chromatograms of Aroclor 1 2 2 1 , Aroclor 1242, Aroclor 1254, and Aroclor U2G0. This is what these products look like to a residue analyst using the most commonly employed detection system. From'these chromatograms, it can be readily seen that we are dealing with multi-component products, which of course, increases the com plexity of assessing every aspect of this problem - relative to a well defined single component system such as DDT. I should mention at this point, that the FCB residues generally found in wildlife are most similar to Aroclor 1254 and Aroclor 1260 chromate grams` The next slide (3) demonstrates that in reality, these materials are even more complex than is generally realized. In the upper right' portion of this slide is again shown a low resolution electron capture gas chromatogram of /^rcclor 1242 under the optimum conditions normally employed by residue analysts. Under these conditions, Aroclor 1242-would appear to be a 15 component system. In the lover portion of this slide is a flame ionization gas chromato gram of the same material using a high resolution S.C.O.T. column. If one carefully inspects this chromatogram, our simple 15 component product has now been resolved into 55 different components. These facts simply indicate that all PCB products cannot be lumped . together in terms of either their environmental impact or persist ence. The. type of biological studies which we have carried out to date are shown in the next slide (#5). For discussion purposes, they can be conveniently divided into two categories: "Primary Bacterial Degradation Studies", an area in which research on PCBs is just beginning, and "Residue Accumulation Studies". Most of our bacterial degradation work has been centered around the fairly well known semicontinuous activated sludge degradation test. Our residue accumulation studies have been fairly extensive and have involved the exposure of better than 2 1 0 0 fish, chickens, rats and dogs to the various Aroclor products; resulting in the collection of over 1200 samples of which approximately 500 pooled samples v/ere eventually analyzed for PCB residues. The prime objective of these studies is given on slide 6 . 1001175 ACM 00 02 27 -i- Sid" The sfi-iii-continuous nettivr.fcnrl uiudqo toni. procedure* unod te evaiurveo the primary bacterial clc-^irn-liitieni rata: Yf fhV Ai-odor produits is the test method recoi'ir.-jrided by tiK: sGi.n ami Detergents Association for the evaluation of the dodogrstlnbij ity of linear alkyl benzene sulfonate typo surfactants [JACCS Yz 9 e (19G5) & 46, 2 (1969}]. . --' w Prima ry niod ceradat icm - Minimum alternation of the chemical structure of\the material in question to an extent that characteristic properties of the original material are no longer evident. , This procedure employs sludge from a sewage treatment plant as the source of microorganisms to which a specific amount of the material being evaluated and a synthetic sewage mixture are fed on a periodic basis in a specially designed aeration chamber. The next slide (#8 ) graphically illustrates what the aeration chamber looks like. It is simply a large glass cylinder with provisions for aeration, auxiliary stirring, a siphon for periodic removal of the supernatant and a septum for introduction of the test material. The mixed liquor (sludge + water) obtained from the sewage treatment plant is initially adjusted with tap water to a suspended solids concentration of about 2500 mg/1 , and 1500 ml of this mixture is then charged to the aeration chamber. The mechanical cycle employed is shown in the next slide (#9). Each cycle is initiated by the addition of the synthetic sewage and 1 mg of the PC3 product being tested. Since the PC3s are quite water insoluble, they are fed to the unit via injection of 200 pis of a concentrated ethanol solution. In this manner, homogenous dispersion of the PCBs on the bacterial sludge is obtained. After about one hour of aeration an aliquot of the mixed liquor is withdrawn from the chamber and analyzed for PC3s via UV spectro photometry and/or electron capture gas chromatography. Aeration is continued for about 43 hours and a second sample is withdrawn for analysis. At this point, the aeration is stopped and the sludge allowed to settle, the sludge volume and pH are then checked to insure that the unit is operating satisfactorily. Two-thirds' of the supernatant is withdrawn and replaced with tap water; aeration is then resumed. The cycle is re-initiated by the addition of the synthetic sewage and Aroclor in question. This cycle is continuously repeated until a steady state and consistent degradation rates are obtained. The per cent degradation rate is calculated as shown in tho equation on the slide from the amounts found in the samples analyzed during each cycle. Degradation testing of the Aroclor products shown in the next slide (l;1 0 ) have been carried out over an eight month period in our laboratories. In this slide, wo have shown graphically the results observed to date. Here we have plotted the mean per cent degradation Fn01176 ACM CCC228 .i \ r a te " f o r lift /iit * r o c l o r I27X"p. MCR 1043 ( n ros^nT'di hvtori.T t ccnV;i5r1r.y 3fit J'*y vvi-irjhtv c h i or ino, Ai uc Ior 101o (4\: ci:.i ovjnq j nro'jj or 1 2 4 ?, nd Avne 1'o r 1X54 versur- tJir: w i g h t . p er c-.:nt*. c h l o r i n e present ill each-. Viu: actual moan per cent rtciij.udaticu rate:; and 9M conf.irtciici; Ijuitn for ev'eh material arc: id.ov.M In tho lover* J o f t portion of 111c ?ilidc:. Th ere data- we rc a]1 ofct-air.t:d by Uv pec tr0J photometry which in essence'f o l l o w s the decrease in the aromatic ring content anti in indicative o f bacterial ring cleavage. The important point to note hero\ i s that as the degree o f chlorination decreases the degradation rate increases. In order to g iv e you a fe e lin g fo r the degradation r a te s observed w ith o th e r m a t e r ia ls , A r o c lo r 1221 d eg ra d es a t abou t th e same r a te a s a n o n - l in e a r AES s u r f a c t a n t . We h a v e a l s o u s e d t h i s te c h n iq u e t o s tu d y p , p r-DDT and have a t t h i s p o in t in tim e n oted no s i g n i f i c a n t prim ary d eg ra d a tio n . The n e x t s l i d e (11) shows th e ch an ges in hon olog d is t r ib u t io n observed fo r A roclor 1242 v ia e le c tr o n capture gas chrom atographic a n a ly s e s . The upper chromatogram shows th e ch a ra cter o f th e r e sid u e one hour a f t e r a d d itio n . The numbers above each peak in d ic a te th e dom inant homolog or hom ologs p r e se n t in ea ch . The low er chromatogram i s o f - th e r e s id u e a f t e r 72 hours o f exp osu re to th e b a c t e r ia l slu d g e . I t can be r e a d ily seen by com paring th e two chromatograms- th a t a l l th e d ic h lo r o b ip h e n y ls , m ost o f th e t r ic h lo r o b ip h e n y ls , and a s i g n i f i c a n t p o r t io n o f t h e t e t r a c h l o r o b ip h e n y ls a r e degraded in 48 hours under th ese t e s t co n d itio n s. The c o n c lu sio n s w hich we draw from t h i s p r e lim in a ry d a ta are shown in the next s lid e (#12). N ext, I w ill d is c u ss our "A roclor R esidue Studies" (S lid e #13). Our w h ite le g h o r n c h ic k e n s t u d i e s ( S l i d e #14) have c o n s i s t e d o f a 90 day o r a l ex p o su re o f A ro clo r 1242, A ro clo r 1254, and A roclor 1260 a t 1 , 1 0 , and io o ppm f e e d l e v e l s and a r e p e a t 90 day stu d y o f A r o c lo r 1242 a t th e 2 , 4 , and 8 ppm fe e d l e v e l s . 336 C h ickens w ere employed from which a t o t a l o f 521 t i s s u e , c h ic k , and egg sam ples w ere c o l l e c t e d . Of t h e s e 112 p o o le d sa m p les v/ere a n a ly z e d fo r PCB r e sid u e s.. In th e n e x t s l i d e (#15) a r e shown th e r e s u l t s o f th e 90 day o r a l e x p o su r e o f w h ite le g h o r n c h ic k e n s t o A r o c lo r 1 2 4 2 . On th e l e f t s i d e , we have shown th e o r a l ex p o su re le v e ls which were 1 , 10, and 100 ppm, th e t h e o r e t i c a l r e s id u e in ppm, which would have been found in th e lip id i f th e ch ick en s had r eta in e d a l l o f the A roclor 1242 w hich th e y o r a l l y i n j e s t e d . As you can s e e , th e s e l e v e l s a r e M .25, 1 2 5 0 , and 1 2 ,5 0 0 ppm. N ext i s shown th e a c t u a l a v e ra g e l e v e l in ppm foun d in th e l i p i d o f th e m u s c le , f a t , and l i v e r sam p les and th en th e l e v e l s foun d a f t e r 30 d a y s on a PCB f r e e d i e t . The im p o r ta n t p o i n t s t o n o te a r c t h a t ^OQZ o f a l l th e A r o c lo r 1242 consumed in d i r e c t l y e x c r e t e d a n d /o r m e ta b o liz e d and t h a t a f t e r 30 d a y s on a PCB f r e e d i e t 3 5 5 , 4 4 5 , and 575 o f th e Pens r o ta in p d a f t e r 90 d a y s o f c o n tin u o u s e x p o su r e a t th e 1 , 1 0 , and 100 ppm l e v e l s was excreted and/or m etab olized . Foni7 7 ADM C0G229 b u V io the ti: d i e t . The number a c r o s s th e to p sim p ly r e f e r to th e number o f c h l o r i n e atoms- p e r - b ip h e n y l m o le c u le . As you can s e e , Aroc lo r 1242 co n ta in s dom inant amounts o f th e d i- through p cn tach lorob ip h e n y ls am f a m in or amount o f h e x a c h lo r o b ip h e n y l / A f t e r 90 days o f ex p o su re th e dicH lorob?. p h en yl was no lo n g e r o b ser v a b le , and th e dominant components were th e t r i - through p en tach loro bip henyl h o m o lo g s. A f t e r 30 d a y s 6n a PC3 f r e e r e c o v e r y d i e t , th e h e x a c h lo r o b ip h e n y l i s now a .dom inant com ponent b e c a u se o f c o n tin u e d e x c r e tio n an d /or n e ta b o lis h o f 'the low er c h lo rin a te d hom ologs. In th e n e x t s lid e - (#16) a re shown th e r e s u l t s fo r th e 90 day o r a l exposure o f A roclor 1254 in w h ite leghorn chickens a t the 1 , 10, and 100 ppm e x p o su r e l e v e l s . The t h e o r e t i c a l r e s id u e s are th e -same as b e f o r e and we h ave a g a in shown th e a c t u a l l e v e l s found in th e t i s s u e s a f t e r 90 days o f c o n tin u o u s ex p o su re and 30 days on a PCB f r e e d i e t . In t h i s i n s t a n c e , ^70-72% o f th e A r o c lo r 1254 in g e s t e d was d i r e c t l y e x c r e t e d a n d /o r m e ta b o liz e d and a f t e r 30 d a y s on a PCB f r e e d i e t , ^ 4 5 3 o f t h e r e s i d u e s r e t a in e d were excreted and/or m etab olized . 1 The homolog d is t r ib u t io n o f th e produ ct and r e sid u e s i s shown on th e r ig h t o f th e s l i d e , tne product A roclor 1254 co n ta in s minor . I amounts o f th e t r i - and h e p ta c h lo r o homo'logs and dom inant amounts o f th e t e t r a - , p e n ta -, and hexachloro b ip h e n y ls. The r esid u e a fte r 90 days o f exp osu re d id n o t c o n ta in d e te c ta b le amounts o f th e t r i - ' ! ch lo ro b ip h en y ls and th e tetra ch lo ro b ip h en y ls v/ere no lon ger a dom inant com ponent. The dom inant hom ologs v:ere p e n ta - and h ex a - chloro b i p h e n y l s . A f t e r 30 days on a PC3 f r e e d i e t , t h e t e t r a c h lo r o b ip h e n y ls w ere now n o t d e t e c t a b l e , th e p e n ta c h lo r o b ip h e n y ls ] were a minor com ponent, and th e h exach loro b ip h en y ls the dominant com ponent. 3 In the next s lid e (#17) are the r e s u lts fo r A roclor 1260. Again, the o r a l exposure le v e l and t h e o r e tic a l r esid u e le v e ls are the same and th e PCB r e s id u e s found i n t h e t i s s u e s a f t e r 90 d ays o f 3 c o n tin u o u s e x p o su r e and 30 d ays on a PCB f r e e r e c o v e r y d i e t a re shown. A f t e r '90 d a y s1o f ex p o su re, 57-525 o f a l l A roclor 1260 consumed was d i r e c t l y e x c r e t e d a n d /o r m e ta b o liz e d and a f t e r 30 d a y s on a PCB f r e e d i e t ^405 o f th e r e s i d u e s r e t a in e d w ere e x c r e t e d .1 an d /or m eta b o liz ed . . A s shown on th e r ig h t , A roclor 1260 c o n ta in s dominant amounts^of 1 p e n ta -, h e x a -, and h e p ta ch lo ro b ip h e n y ls and a minor amount o f o c t a c h lo r o b ip h e n y l. The r e s id u e s a f t e r 90 d ays o f ex p o su re and 30 days on a PCB f r e e r e c o v e r y d i e t c o n t a in m inor amounts o f th e p e n ta - 1 and o c ta c h lo r o h o n o lo g s. In both c a s e s , th e dom inant homologs were th e hexa- and h ep ta ch lo ro b ip h e n y ls. Our a lb in o r a t work ( S l i d e #18) h as c o n s i s t e d o f 30 day o r a l , 2 y ea r ch ron ic o r a l and a 3 g en era tio n r a t rep rod uction exposure study with A r o c lo r 1 2 4 2 , A r o c lo r 1 2 5 4 , and A r o c lo r 1260 and a 90 day su b a c u te I Foni178 *1 ADM 0 0 0 2 3 0 #7.1 fVotii wftitrft* aiiouJR xrtt nin ,t .inik' fo tn a in p l s* ' B*ir<r'OTlCCQ!i(t Two5hnndjcitl- o i: H ir-n~ 'nruVlysea f o r PCB r e s id u e .'. " "" Iii th e n e x t 9l i d o (519) a rc shown th e r e s u lt s o f our two year c h ro n ic o r a l exposu re stu d y o f A ro clo r 1212 in a lb in o r a t s . The o ra l exposure l e v e l s w ere 1 1 0 , and 100 ppm and th e t h e o r e t i c a l r e s id u e s wore v.300, fiOOO, 0 0 ,0 0 0 ppm, r e s p e c t i v e l y . The a c t u a l r e s id u e s found in th e t i s s u e l i p i d are. shown a f t e r 3 , 1 2 , and 24 months o f exD osu re. Com parison o f th e r e s id u e s found a f t e r 24 months to th e t h e o r e t ic a l r e s i d u e l e v e l s i n d i c a t e s t h a t 99% o f th e A r o c lo r 1242 fe d was d ir e c tly excreted and/or m etab olized a t a l l exposure le v e ls . As i s shown on t h e r i g h t , A r o c lo r 1242 c o n t a in s dom inant amounts o f th e d i - th rou gh p e n ta c h io r o b ip h e n y l hom ologs and a m inor amount o f th e h e x a -. The r e sid u e s a f t e r two y ea rs d id n ot co n ta in a s i g n i f i ca n t amount o f th e d ic h lo r o b ip h en y ls and th e dominant components were th e t r i - , t e t r a - , and p en tach ioro bip henyl hom ologs. In th e n e x t s l i d e (#20) are shown th e r e s u lt s o f th e two year ch ro n ic o r a l exp osu re o f a lb in o r a t s to A ro clo r 1254. The exposure and t h e o r e t i c a l r e s id u e l e v e l s a re th e same a s w ith A roclor 1242. The r e s id u e s found a f t e r 3 , 1 2 , and 24 months o f ex p o su re are a l s o shown. Comparison o f th e r e s id u e s a f t e r two y ea rs to th e amount in g e ste d < d e m o n str a te s t h a t 95-98% o f th e A r o c lo r 1254 consumed i s d i r e c t l y excreted and/or m etab olized . The hcm olcg d is t r ib u t io n o f A ro clo r 1254 and th r e s id u e s are shown on th e r i g h t . A r o c lo r 1254 c o n ta in s m inor amounts o f th e t r i - and h cp ta ch lo ro b ip h en y l hom ologs and dom inant amounts o f th e t e t r a - , p e n ta -, and h ex a ch lo ro b ip h en y l hom ologs. The r e sid u e s d id n ot co n ta in d e te c ta b le le v e ls o f th e tr ic h lo r o homologs and the t e t r a c h lo r o b ip h e n y ls w ere no lo n g e r a dom inant com ponent. The dom inant homologs were th e p en ta - and h exachloro b ip h e n y ls. The n e x t s l i d e (#21) sh o w s'th e th e r e s u l t s fo r th e two y e a r exp osu re o f A roclor 1260 in a lb in o r a t s . A gain, the exposure and th e o r e tic a l r e s id u e l e v e l s a re th e same and th e r e s id u e s found in th e t i s s u e s a f t e r 3 , 1 2 , and 24 m onths o f e x p o su re a re shown. In t h i s c a s e 93-95% o f a l l A r o c lo r 1260 in g e s t e d was d i r e c t l y e x c r e te d a n d /o r m etabolized. The dom inant hom ologs in A ro clo r 1260 and th e r e s id u e s is o la t e d . from th e t i s s u e s were s im ila r in a l l c a s e s . In ord er to d em on strate th e r e la t io n s h ip betw een r e s id u e sto r a g e l e v e l s and th e d e g r ee o f c h lo r in a t io n o f th e product fe d ( s lid e # 2 2 ). I h ave p l o t t e d t h e a v e r a g e ppm PCO foun d i n th e l i p i d v s th e w e ig h t per cen t c h lo r in e in th e produ ct fe d . These d ata were taken from our 90 day su b a c u te a lb in o r a t s t u d ie s w ith A ro clo r 1 2 2 1 , A ro clo r 1 2 4 2 , A r o c lo r 1 2 5 4 , and A r o c lo r 1260 a t an e x p o su re l e v e l o f 100 ppm. As von can s e e , th e r e s id u e s to r a g e l e v e l s d e c r e a se e x p o n e n t ia lly as the w eight per cen t c h lo rin e d ec re a ses, sim ply dem onstrating the r e la tio n s h ip betw een th e h ig h er homolog co n ten t o f an A roclor product and th e tis s u e sto ra g e le v e l.- FOOl 1 7 9 ACH 0G0231 The n e x t s l i d e '(524) sh ow s th e r e s u l t s o f on e two y e a r s tu d y o f A r o clo r 1242 a t e x p o su r e l e v e l s o f 1 , 1 0 , and 100 ppm. in t h i s stu d y , th e t h e o r e t ic a l r e s id u e l e v e ls arc ^500, 5000, and 50,000 non r e s p e c t i v e l y . Vie h a v e a l s o sl\own on t h i s s l i d e t h e r e s i d u e l e v e ls " ' found a f t e r two y e a r s o f ex p o su re and a f t e r 30 and 60 day p e r io d s on PC3 f r e e r e c o v e r y d i e t s . The b e a g le d o g s d i r e c t l y e x c r e t e d a n d /o r m e t a b o liz e d 99.6% o f t h e A r o c lo r 1242 consum ed and a f t e r 60 days on PC3 f r e e d i e t s , 50-60% o f PCS r e s i d u e r e t a i n e d a f t e r two y e a r s o f exposure was e x c r e te d an d /or m eta b o lized . A roclor 1242 c o n ta in s dom inant amounts o f th e d i - , t r i - , t e t r a - , and p en ta ch lo ro hom ologs and a m inor amount o f th e h ex a - hom olog. The r e sid u e found a f t e r two y e a r s o f exp osu re co n ta in ed no d e te c ta b le l e v e ls o f th e d ic h lo r o hcm.olcgs and dom inant l e v e ls o f th e t r i - , t e t r a - , h e p ta -, and o c ta c h lo r o b ip h e n y ls . The p en ta ch lo ro hcm olog, ` alth ou gh dom inant in th e p rod u ct fe d , was n o t a dom inant component o f th e r e s i d u e . A f t e r 30 d a y s on a PC3 f r e e r e c o v e r y , d i e t , t h e d i - , t r i - , and te tr a c h lo r o b ip h en y ls were n ot d e te c ta b le components o f t h e r e sid u e . At t h is p o in t, th e dominant components were th e h e x a -, h e p ta -, end o c ta c h lo r o b ip h e n y ls. The tren d toward e x c r e tio n a n d / or m etabolism o f th e low er c h lo rin a te d hom olcgs continued to the exten t th a t a fte r 60 days on th e recovery d ie t th e hexachloro biphenyl was no lo n g e r a dominant com ponent, and th e h e p ta - and o c ta c h lo r o b i p h en yls became th e dominant c o n s titu e n ts in th e r e sid u e . In th e n ext s l i d e (25) a re th e r e s u lt s fo r th e two y ea r exposure o f b ea g le dogs to A roclor 1254. The o r a l exposure and th e o r e tic a l r e s id u e l e v e l s a r e t h e same and t h e PC3 r e s id u e l e v e l s foun d in th e t i s s u e s a f t e r two y e a r s o f ex p o su re and a f t e r 30 and 60 day p e r io d s on PCli f r e e r e c o v e r y d i e t s a r e a g a in show n. In t h i s in s t a n c e , th e d ogs e x c r e te d a n d /o r m e ta b o liz e d 98-99% o f a l l A roclor 1254 consumed o v e r a two year p e r io d . A fte r 60 days on a PCS f r e e r e c o v e r y d i e t , 30-40% o f t h e r e s i d u e s r e t a in e d w ere excreted and/or m eta b o lized . The product fe d , A roclor 1254, co n ta in s minor amounts o f th e t r i - and h ep ta c h lo r o b ip h e n y ls and dominant amounts o f th e t e t r a - , p e n ta -, and h e x a c h lo ro hom ologs. A fte r two years o f ex p o su re, th e r e s id u e r e ta in e d from th e product did n o t. contain d etecta b le le v e ls of the t r i - or tetrach loro bip henyls, the p e n ta -, and h ex a ch lo ro b ip h e n y ls rem ained dom inant com ponents, and th e h ep tach loro b ip h en y ls became dominant c o n s titu e n ts . A f t e r 30 days on th e PCD f r e e r e c o v e r y d i e t , t h e p e n ta c h lo r o hom ologs became a minor com ponent o f th e r e s id u e , th e h ex a - and h ep ta ch lo ro b ip h e n y ls rem ained d om in an t com ponents and th e o c t a c h lo r o homo lo g s f ; became a m inor com p on en t. A f t e r 60 c a y s on th e PC3 f r e e r e c o v e r y O d ie t , the pentachloro bip h en yls vara excreted and/or m etabolized to the e x te n t th a t th e o c ta c h lo r o homologs became a dominant c o n s titu e n t of the resid u e. 1001180 ADM OOC23 t V- The n e x t slide* (52C> shows the* results for the two year oral exposure residue study of Aroclor 1260 in bene;la dogs. The c'-j^su-cr and theoretical residue levels are the same a:; tho*;c for the Aroclor 120. and Aroclor 1254 studies. Next is shown the residues, v/hich accumulated after two years of continuous exposure and the residues retained after 30 and CO day recovery periods on PC3 free diets. With this Aroclor 93-9Dt of tl^e amount consumed over two years was directly excreted and/or metallized. After 60 days on the recovery diet ^13t of the retained residues were excreted and/or metabolized. The homolog distribution of Aroclor 1260 is as shown, dominant amounts of the penta-, hexa-, and heptachloro biphenyls with a minor amount of the octachloro homologs. After two years, the PC3 residue contains no detectable level of the pentachlcro homologs, a minor amount of the heptachloro biphenyls, and dominant amounts of the hexachloro and octachloro homologs. After 30 days on the recovery diet, the dominant homologs are new the hexa-, hepta-, and octa chloro biphenyls becoming a dominant component of the residue via loss of some of the hexachloro biphenyls. After 60 days on the recovery diet, the hexachloro biphenyls are no longer dominant components of the residue and it is now mainly the hepta- and octachloro biphenyls. , The next slide (#27) illustrates the residue fall off as a function of Aroclor and recovery period. These data are from the two year beagle dog studies and the exposure level is 1 ppm. In this graph, I have plotted the average ppm ?C3 found in the lipid for Aroclor 1260, Aroclor 1254, and Aroclor 1242 after two years of continuous oral exposure and then after 1 month and 2 month recovery periods on PCB free diets. This plot simply demonstrates that the PC3 residues retained from Aroclor 1242 fall off more quickly than those retained from Aroclor 1254 and Aroclor 1260. ?he table in the next slide (#2S) shows the relative ability of fowl, small mammals, and large mammals to retain orally ingested PC3s. These data are for Aroclor 1242 at the exposure levels and periods shown. The concentration factor is calculated by dividing the '.aximum PC3 level found in the lipid by the exposure level. As you ran see from the factors, chickens retain PC3s to a greater extent han do rats or dogs. ur fish residue work is not very extensive at this point rimarily because we have had problems in finding consulting aboratories capable of carrying out dynamic low level fish exposure tudies, and secondly, because government laboratories such as those n Duluth, Minnesota, Columbia, Missouri, and Gulf Breeze, Florida are, and are, still in better positions to carry out and evaluate hese types of studies. a have done some very preliminary 21 day dynamic exposures of cat-sh and blucgiil fingcrlings to some of our Aroclor products and - generally supports the conclusions which can be drawn from .taratare data. '.c general conclusions which wc draw frem these residue studies are iown in the next three slides. Mirti 181 S l i d e 31 r A l t e r a t i o n o f Ilomolcg D i s t r i b u t i o n - C o n c lu sio n s * In summary, we f o o l th a t th e r e s u l t s o f our p r e lim in a ry resea rch su pp ort, what has and i s b eip g observed v ia r esid u e a n a ly sis of e n v ir o n m e n ta l sam p les? t h a t %s t o s a y , from a r e s id u e v ie w p o in t, t h a t t h e b u lk o f t h e PC3 hom ^logs r e l e a s e d t o th e en viron m en t (PC3s w ith le s s than 5 c h lo rin e s) are su b je c t to environm ental degradation o f one s o r t or an oth er a t m easurable r a te s and as such have n ot accum ulated. E. S. Tucker 'O ) Ennii82 a0K 0 0 0 2 3 * ' I OPERATING INSTRUCTIONS * DEPARTMENT 246 .' STILL OPERATOR O ctober, 1974 SECTION V HATERIAL HANDLING 6 TOXICITY DATA SECTION VI A. BATCH BLOW. TANKS B. VACUUM JETS ' C. #3 AND.4 STILLS D. POROCEL TREATMENT E. THERMINOL FURNACE W ritte n b y : T N. C arrico R eview ed b y : G L. Johnson / tm IW1183 100107 jJhj^AKTrthNT 246 OPERATING INSTRUCTIONS SECTION V - MATERIAL HANDLING AND TOXICITY DATA AROCLORS A r o c lo r s ms m a n u f a c tu r e d i n D e p a rtm e n t 246 a r e n o n - f la m m a b le l i q u i d s v h lc ^ may v a ry g r e a t l y I n v i s c o s i t y a t room te m p e r a t u r e . C ontact w ith th e sk in sh o u ld be av o id ed . In case o f s p i l l s on th e b o d y , w ash th e a f f e c te d a re a s w ith soap and w a te r. In h a le -* t i o n o f A r o c lo r an d Honta^p fu m es s h o u ld b e a v o id e d a s t h e y a r e h ig h ly to x ic P ro te c t th e s k in , lu n g s, and eyes by w earing p ro te c tiv e c lo th in g , r e s p ir a to r , and g o g g le s. I f s p i l l e d `on c lo th in g , change to c le a n ' c lo th e s BIPHENYL ' . B ip h en y l i s a flam m able liq u id re c e iv e d in ta n k c a r s from o u r A n n is to n , A labam a, p l a n t . I t i s h e a te d to 95"C and u n lo a d e d to t h e E a s t B10 s t o r a g e t a n k . I t i s t r a n s f e r r e d d a i l y t o t h e c o n tin u o u s , c h l o r l n a t o r s , th e c a t a l y s t m ix ta n k , a n d when n e c e s s a r y to th e head, ta n k fo r th e b a tc h c h lo r ln a to r s . th sy stem is e s s e n tia lly clo sed . B ip h en y l i s a solid* a t am b ien t te m p e ra tu re , th e f la s h p o in t i s 113*C , th e X -p o in t i s 68*C. The fum es a r e n o t d a n g e ro u sly d e a d ly , b u t-th e y a re po iso n o u s o v er a p ro lo n g ed tim e. B re a th in g la rg e am ounts o f v a p o r o r d u s t can c au se dam age to r e s p ir a to r y p a s s a g e s . V e a r g o g g l e s w h e n t r a n s f e r r i n g o r s a m p l i n g B10 f r o m t a n k c a r s o r sto ra g e tan k s. . I f m o lte n B ip h en y l I s s p ille d on th e s k in i t sh o u ld b e 'a b s o rb e d w ith a c le a n c lo th and th en w ashed w ith a lco h o l fo llo w ed by la rg e q u a n titie s o f w a te r, o r i f allo w ed to s o lid ify i t sh o u ld be scrap e d o ff and th en w ashed w ith w a te r. I f s p ille d on c lo th in g , - change to clean c lo th e s. CHLORINE i C h lo rin e i s d e liv e r e d by p ip e lin e from th e c h lo rin e d e p a rtm e n t, and i s used to c h lo rin a te b ip h e n y l to produce v a rio u s A ro c lo rs. i t I s a gas u n d e r' norm al c o n d itio n s and i s v e ry tox ic. A co n c e n t r a t i o n o f * 1 ,0 0 0 ppm w o u ld b e f a t a l . At tim e s , le a k s do o c c u r w hich w i l l l i b e r a t e c h lo r in e g as in to th e a ir ,. Cas m asks a re p ro v id e d in th e .departm ent and a re s u f f ic ie n t fo r sm all leak s* . A S co t-A ir-P ak I s p ro v id e d fo r la rg e gas re le a se s. Foni14 100108 DEFT. 246 - OF*., .TING INSTRUCTIONS SECTION V - MATERIAL HANDLING AND TOXICITY DATA NATURAL CAS ' _ N a tu r a l Gas I s s u p p lie d by I l l i n o i s D over and I s a m ix tu re o f M ethane, E th an e, and h sm a ll amount o f Propane. N a tu ra l gas i s e s s e n t i a l l y o d o r le s s , how ever, a sm all amount o f M ercaptan i s added to gi^ e i t a c h a r a c t e r is t ic , pungent o d o r. I t i s lig h t e r than a ir and c o lo r le s s ,* and very flam m able. HC1 OFF-GAS ; . Hydrogen c h lo r id e i s a by-product o f the ch lo rin a tio n of b ip h e n y l. The gas i s c a r r ie d by p ip e lin e to D ept. 217.. I t i s a gas under norm al c o n d itio n s and i s very t o x ic . A c o n c e n tr a tio n o f 1 5 0 0 -2 0 0 0 ppm w ou ld b e f a t a l i n a few m in u te s . Do n o t rem ain in an a r e a w h ere enough HC1 g a s i s p r e s e n t to c a u se d is c o m f o r t in b r e a t h in g . Gas m asks a re .p ro v id ed i n th e departm en t and are s u f f ic ie n t fo r 's m a ll le a k s. A Scot-A ir-P ak i s provided fo r large gas r e le a se s. I f sk in i r r it a t i o n s p e r s is t , wash th e area w ith la r g e amounts o f w ater, then report to the dispensary. FERRIC CHLORIDE F e r r ic c h lo r id e i s p u rch ased in 'two pound p l a s t i c b o t t l e s fo r use as a c a ta ly s t in the c h lo r ln a to r s I t i s a so lid - under norm al c o n d i t i o n s and i s n o t c o n s id e r e d t o x i c . Some p e o p le may b e a l l e r g i c and d e v e lo p a. s k in r a s h . G loves s h o u ld be worn t o p r o te c t the. hands and th e eyes must be p ro tected to keep F e r r ic C h lorid e d u st-fro m b lo v in g in .th e m . Large amounts o f w ater sh ould be used to wash any ir r ita te d a rea s. LIME-- i '* ' Lime i s h a n d led in h a g s and i s n o t d a n g er o u sly t o x i c , and i s regarded a s more o f a n u isa n ce. I t i s very hazardous to the e y e s, th e r e fo r e , g o g g le s sh o u ld he worn when h an d lin g i t . Large q u a n t it ie s o f w a ter sh ou ld be used -to flu s h lim e from th e e y es and fu r th e r tre a tm en t sh ould be g iv en a t the d is p e n sa r y . G loves should be worn fo r g en era l sa n ita tio n to keep lim e o ff the sk in and c lo t h in g . - ATTAPPLCUS EARTH ' . A ttap u lgu s ea rth i s handled In bags and i s not t o x ic . As*a m atter o f g e n e r a l c L e a n lln e s s , i t sh o u ld be k e p t 9 f f th e s k in and c lo t h in g . Fnmi85 100100 t)Lb i AV. V Xirt i AL HANDLING AND TOXICITY XA POROCEL / P o r o c e l 1* bu n d led i n bags and I s qo c o n sid e r e d t o x i c or v dangerous. I t Is used as the s a te r ia l to upgrade e le c t r ic a l p r o p e r tie s o f A roclor passed thru the a b so rb ers. H andling would p r e se n t a hazard to th e e y e s , th e r e fo r e , g o g g le s sh o u ld be worn when h a n d lin g t h i s m a te r ia l. IOM186 J 100U0 B U L L E T I N n o . ic.PP 3gR (RV'Wd 197PI TRANSFORMER Inspection & Maintenance Guide i% Monsanto T(UMDf De1JfIfliS SECTION A. T R A N S F O f M f l 4 ? K A f t E L S .......................... .............. 1 I. IngWMWti m ............................................... 1 II. HNwry Nam T y p e ................................ 1 Table I -- Tpe Composition of Transformer Askarel! .............................. 2 I II . Interchangeability ....................................................2 IV . Table II - Official Transform v Adtarel Shipping S p ec ifica tio n s........................................... 3 V . Ordering Instruction .............................................. 2 V I. S t a b ilit y ....................................................................... 2 V I I. Precautions Whan Handling Drums. Tank Cart and Whan Opening Transform ers.......................... 2 A. Keao Dry Curing Handling ............................. 2 Table III - Handling and Pumping Tem peratures..................................... 4 B. Use Ordinary Personal Precautions ...............4 C. Precautions on Opening an Askarel T ran sfo rm er...........................................5 V I I I . Avoid Environmental P o llu tio n .............................5 1. Labeling Askarel Transform ers....................... 6 2. Disposal of Liquid and Solid Wastes ............ 6 3. Conditioning of New or Recycled Askarel .6 4. Teardown of Transformers for Repair or Scrap ...........................................7 5. Transformer O is p o s a l........................................ 7 IX . E x p e c t^ Service L i f e ............................................. 7 X . General Charecteriitics of Transform Adtarel F lu id .................... 7 X I. Sampling Transformer A dearel Fluid ................. 3 X II. Evaluation of Adtarel Racaived in New E q u ip m e n t...................................................8 X III. Dielectric Breakdown Voltage - Mo inure Relatwndiip ..............................................9 Table IV - Relation of Dielectric Breakdown Voltage to Am ount of Dissolved Water in Askarel and Mineral O i l .......................................... 9 Table V - Approximate Solubility of Water in Transformer Askarel and Mineral Oil . . . . 10 X IV . Turbidity ......................................... 10 X V . Check Pointi for Maintaining Adtarel Insulation .................................................10 A. General Considerations ................................... 10 B. Modern Sealing Procedures ................. . . 11 C. The Older Sealing Arrangem ents.................. 12 X V I. Periodic Fluid Inspection and ' What Checkpoints Mean ......................................12 A. Visual Inspection .............................................. 13 B. Dielectric Breakdown Voltage ..................... 13 X V II. l m p e d w C h e * l l * .............................................. 13 X V III. in Transform ers......................... 14 (ffe c t of Common Imutation Power Factor and .............................................. 14 T 4 V 9 A B -- Effect of Common I mu Iat ion M s -rfid i an Volume Resistivity XIX . of Adtarel . . ............................................................ 14 ASTM Method for Inw et gating the Compatibility of Transformer Insulation and Construction Materials in A ik a r s is .............15 X X . Refining Adtarel for R e - U a ................................ IS A. Filtering Through Ory Blotter Paper to Remove Moisture and Extraneous. P anicles........................ 15 X X I. X X IL Table VIII- Water R emovai byFiltering Askarel Through a Paper Press B. Disposal of Solid Wastes C. Solid Insulation Requiring Drying D. Earth Treatment for Maximum Improvement of Power Factor and Volume Resistivity Table IX - Effect of Power Factor and Volume Resistivity Cleaning Arced Transformers Sampling A d t a r e l................... . . 16 . . 16 - 16 1o 17 17 17 SECTION B ASKAREL F IL L E D SWITCHES AND TERMINAL CHAMBERS ........................ig I. In tr o d u c tio n .............................. ' _ jg II. Sources of Contamination . . . 19 *20III. Sealing Switches and Terminal Chambers . . IV . Adtarel Used Under Mild Arcing Conditions 20 V . Maintenance for Adtarel Filled Switches . . . .20 V I. Askarel Under Excessive Temperature or Fault Conditions ............................................21 SECTION C T O X IC IT Y A N D SAFE H A N D L IN G .............. ........... 21 I. In h a la tio n ............................................................... 21 II. Skin C o n ta c t..........................................................21 SECTION D A N A LYTIC A L SERVICES ON TRANSFORMER A5KAREL A V A IL A B L E FROM MONSANTO .................................22 Types of Analyses Available: ............................................. 22 1) Routine Maintenance C h e c k ...................................... 22 2) Complete Analysis................... ..................................... 2. 3) Analysis After Earth Refinement ........................... 2 SECTION E A P P E N O IC E S ......................................................................... 23 Appendix A - Askarel Stability and Composition of Arc Formed G a s .....................................23 Appendix B - Solubility of Gas in Transformer Ask arils ........................................................23 Appendix C - Effect of Temperature on Oietectric Breakdown Voltage of Askarel .................... 23 Appendix 0 - Comparison of the Approximate Viscosity m Say bolt Uni venal Seconds of Transformer A skarili and Mineral O i l .............................24 Appendix E - The Density of Inerxeen 54201 KA 7336-9 and Transformer Pyranol A 1 3 8 3 B - 3 ............................................................. 24 Appendix F - Thermal Conductivity Values * of Transformer Pyranol A 13B 3B -3..................................24 Appendix G - Heat C a p a c ity ............................................ 24 Appendix H - Coefficient of Expansion......................... 24 Appendix I - Fire Resistance............................................ 24 Appendix J - Seals, Properties and Procurement ................................................................25 Appendix K - Caution L a b e l .............................................25 NO TICE: "Nothing contained herein is to be construed as a recommendation to use any product in conflict with any patent. M O NSANTO MAKES NO W A R R A N TIES AS TO THE FITNESS FOR A PARTICULAR PURPOSE OR 6M E R C H A N T A B IL IT Y OF A N Y PRODUCT R E FE R R P TO. no guarantee of satisfactory results from reliance uc on contained information or recommendations, and dn claims ail liability for any resulting loss or damage." FAdl 188 ADM C C 1 S 8 1 A- 'i -- ----------TM==T- TI r.~ visi **.*.* ^ r *' *' *' r* . K*j. n .-. ~'-j'~ : ^ wwWh*| and creating of the n ipared H a i tn ...w dererioretion, liquid taep sge et uualty pmam -:2 V~ U? aktnLQ. repack with a SHareie rin f type*g a*a"*t< * * shaft. If VT. Askarei Undar Excatsiw Ttmportture Conditions Fault The IEEE Guida also points out that, "Chlorobenzenes iaad In transformar tskardi begin to boil at tamparaturas of about 205*C, undar atmospharic conditions. If tha material is haatad to sudi high tamparatura in a talad systam pressura davalops. Pressure w ill also davalop in tha systam if tha aikaral is arcad sufficiently to generate copious h y d r o g e n chloride gas. T h e re fo re , it is recommended that wharavar pou iblf, sealed tskarel-fiUad equipment be provided w ith pressure relief dvices. These devices must be large enou^i to provide immediate relief at a definite pressure, and to prevent further build up of pressure if decomposition continues. It must be remembered that the presence o f devices o f this sort does not necessarily preclude tha rupturing of containing'veads, since pressure build up cm be extremely rapid under violent arcing conditions.'*I., 9 @(tom (D Toxicity& Safe Handling I. Inhalation A t ordinary temperatures tha chlorinated biphenyls in Askarei have not presented industrial toxicological problems. The hazard of potential toxic axposura varies w ith their volatility: tha lower-chlorinated, morevolatile ones present more of a potential problem from the standpoint o f both inhalation and skin contact. When Askarei fluids ire used at elevated temperatures, engineering controls must be applied, either by the use o f d o d systems or by effective local-exhaust ventilation togdhar with general workroom exhaust. Vapor o f Askarei at room temperature duxild not be breathed in a confined a c e , and no vapor o f any fluid evolved at elevated temperatures should be allowed to be diqMrsed into the general i."* Si-4. Inhalation tests on animals indicata that the maximum safa concentra tion o f vapor is in the rangs of from & 5 to 1.0 milligram pw cubic merer o f air. The threshold lim it value (maximum allowable concen tration o f an ho u r working day) sat by the American Conference o f Government Hygienists ere 1.0 milligram o f tha lower-chlorinated biphenyl compounds per cubic merer of air and 0.5 milligram of it m ora-hiitv-chtorinattd compounds, per cubic merer of air. II, Skin Contact Pro lon g ^ o r repeared ddn contact with the Aafcaral fluids must bo avoided by the use o f doves and p ro active gremenn. beewse of it possible occurrence o f condition called ch loracne. Althoudi reports o f this condition caused by Aakarel era rare, it can be produced by e * a v e skin contact. If tha fluid Is apitled on the dein the skin should bo wedred in tire usual mannar with soap m futian. A bum caused by contact with a hot Aakarel dioufd ba treated like any ordinary hunk For dlm osti Instructions o f A durel fluids, sm Section A * V I II , p a p 0. 1(1(111 M9v *9^.V(<t ADM 002002 /I 1 < 'r % Monsanto TO (NOUSTmAL CHEMICALS CO. N. Lindbirgh Boulavard St. Louis. Missouri 63166 Phons. OU) 694-1000 September 22, 1977 L^O f / wWCCiALTY CHEMICALS OVJSIOI Dick Jones, Senior Buyer 9yyr Westinghouse Electric Corporation ^69 Sharpsvllle Avenue Sharon, Pa. I6A16 Dear Mr. Jones: As y o u know, M o n s a n to w i l l c o m p l e t e l y w i t h d r a w a s a s u p p l i e r o f PCB d i e l e c t r i c s O c t o b e r 31 * 1 9 7 7 . C o n c u r r e n t w i t h t h i s * w i t h d r a w a l d a te , Monsanto w ill stop making a v a ila b le to ask are l users the "Transform er Askarel In sp e ctio n and Maintenance Guide", B u lle tin No. I C / F F - 3 8 R - 2 . A l t h o u g h o p e r a t o r s o f a s k a r e l t r a n s f o r m e r s have u s e d t h i s a s k a r e l g u i d e a s a r e f e r e n c e m a n u a l i n t h e p a s t , environ m e n t a l r e g u l a t i o n s on PCB's a r e c h a n g i n g r a p i d l y and h a v e made t h e b u l l e t i n o b s o l e t e . T h i s b u l l e t i n w i l l n o t be u p d a t e d . (May I suggest th a t you destroy a l l copies in your f i l e s and o ffice s so we d o n ' t i n a d v e r t e n t l y s u p p l y o b s o l e t e i n f o r m a t i o n t o t h e industry.) yo u r e c o g n i L _ ____ __ ____ _____ _ ___ _______ s h o u l d n o t be r e l i e d upon now o r i n t h e f u t u r e . Sincerely, tmc r\ SJ* - * i U ~ !L.. A. A l l e y 1'- Industry Specialist D ielectrics RUM190 a unit ol Monaanto Company 100324 UNITED STATI S S &-rVJ - - ENVIRONMENTAL PROTECTION AGENCY ^ J WASHINGTOIM. D.C. 20460" "-- ----------- OCT 171975 OFFICEOF ENFORCEMENT Monsanto I n d u s t r i a l C hem icals Company 800 N. L indbergh B oulevard S t. L o u is, M issouri 63166 00122^375 G entlem en: Recent governmental sampling data In d ic a te the presence of P o ly c h lo r in a te d B iphenyls (FCBs) and com parable chem ical su b sta n c es in the a i r , in w ater bodies, and in fis h in sev eral areas of the country. In o rder to determ ine the n atu re and e x ten t of the possib le a d v e rse e f f e c t s r e s u l t i n g from th e p re se n c e of PCB compounds in th e environm ent, th e Environm ental P ro te c tio n Agency (EPA), in cooperation w ith o th e r fe d e ra l and Scata a g e n d a s , is attem pting to determ ine the s o u rc e s and amounts o f PCBa e n te r in g th e environm ent. I t i s Im p o rtan t th at th is e ffo rt be carried out v ith o u t delay. I t i s o u r u n d e rsta n d in g t h a t your company h a n d les PCB compounds o r m ixtures o r comparable chem ical substances in i t s o p eratio n s. I am th e r e f o r e r e q u e s tin g , p u rs u a n t to th e a u th o r ity p ro v id ed by S e c tio n 308 of th e F ed eral W ater P o llu tio n C ontrol A c t, as amended, 33 U.S.C. 1318, end S e c tio n 114 o f th e Clean A ir A ct, as amended, 42 U .S.C . 1857c-9, t h a t your company f u r n is h EPA w ith In fo rm a tio n p e r ta in in g to your u se end h a n d lin g o f PCBa and com parable chem ical su b stan ces. In a d d itio n to a g en eral d e s c rip tio n , which should include inform ation as to sources, q u a n titie s , uses, and u ltim ate d isp o sitio n , you should respond in d e ta il to the enclosed q u e stio n s. I f any question i s n o t a p p lic a b le to your company o r o p e ra tio n s , p le a s e so in d ic a te by responding "not ap p lic ab le ." a The in fo rm atio n req u ested h e re in must be provided notv i the tending I ts possib le ch aracterizatio n as co n fid en tial Inform ation or trade ' s e c re ts . Should you so re q u e st, bowevsr, any inform ation (other than e f f l u e n t Or e m issio n d e ta ) w hich th e A d m in is tra to r o f t h i s Agency detcgjjaes .to c o n s titu te methods o r processes e n title d to p ro te c tio n k% aa t f l t t e s e c r e t s w i l l be m ain ta in ed ap c o n f i d e n t i a l , p u rsu a n t to p r o e i K r e s s p e c if ie d I n 40 CFR P a r t 3* 1001191 ADM 0 0 6 2 9 0 2 .W ithin 14 days o f r e c e i p t of t h i s l e t t e r , your company must p ro v id e T i l in fo rm atio n concerning your c u rre n t s ta tu s and a c t i v i t i e s and covoslng th e 'tw e lv e month p erio d im m ediately preceding re c e ip t of i. - ,, h i "******. - W ith in 30 days fo llo w in g r e c e i p t o f t h i s l e t t e r , your company must provide a l l Inform ation fo r a l l of the p rio r years Indicated. The Inform ation req u ired h e re in should be sen t d ire c tly to th e addr e s s I n d ic a te d below . I f you have any q u e s tio n s you may c a l l t i e p e r s o n 'in d ic a te d below o r Mr. Blake A. B ile s o f our o f f ic e *202,V.755-*7M . We a p p r e c ia te y o u r prom pt c o o p e ra tio n In t h i s m a tte r. Enclosure R eg io n al C o n ta c t : . - ' * Mr. E a r l J . St#penbft D ire c to r, Enforcement D ivision Environm ental P ro tec tio n Agency 1735 B altim ore Kansas C ity , M issouri 64108 Telephone: (816) 374-2576 i vH i \ \4 \ * 1001192 ADM 00 6 2 9 1 V \ -* ** . POLYCHLORINATED BIPHENYL (PCB) COMPOUNDS OR MIXTURES --- V i W ith in 14 days o f r e c e ip t o f t h i s l e t t e r , your company o u s t p ro v id e <11 in fo rm ation concerning your c u rre n t s ta tu s and a c tiv itie s -e n c o v etin g th^tw elve month period im m ediately preceding re c e ip t of th is le tte r. *1 W ithin 30 days follow ing re c e ip t of th is l e t t e r , your coapany su et provide a l l inform ation fo r a l l of the p rio r years indicated. FOR PURPOSES OF THIS LETTER, THE PHRASE "PCB COMPOUND OR MIXTURE11 INCLUDES ALL CHEMICAL SUBSTANCES KNOWN OR BELIEVED BY YOU TO BE PCB COMPOUNDS OR MIXTURES OR OF A SIMILAR CHEMICAL NATURE, IRRESPECTIVE OF TRADE NAME, AND SPECIFICALLY TNCLimTWfi * CHLORINATED TERPHENYLS.. 1 . .. For each PCB compound o r m ix tu re produced o r iaafigyyy^by your company, f o r each company f a c i l i t y , d u rin g each y ear of 1971. 1972. 1973^131A^_and th e f i r s t two q u a rte r of 1975: _ I a The t o t a l amount o f each PCB compound o r m ix tu re produced or Im ported. b . The name end a d d re ss o f eech o f your company's f a c i l i t i e s w hich h a n d le PCB compounds o r m ixtures* (in c lu d in g p ro d u c tio n f a c i l i t i e s and w holesale end r e t a i l o u tle ts ) , end th e' .+ ^ amount o f each PCB compound o r m ix tu re d i s t r i b u t e d through each fa c ility . e . The name end a d d re s s o f eech c u e to n e r o f te c h PCB compound' o r m ix tu r e , th e amount o f eech PCB compound o r m ix tu re obtained by each custom er from eech f a c i l i t y , end each c u a to m e r'e d e liv e r y p o in t( a ) f o r th e r e c e i p t o f each PCB compound o r m ix tu re. 2 . For eech PCB compound o r m ix tu re in c o rp o ra te d by your company ' k in to l t e p ro d u c ts , f o r eech company f a c i l i t y , d u rin g each year of 1971, 1972, 1973, 1974, end th e f i r s t two q u a r te r s of 1975* a m* A d e s c r i p t i o n o f eech p ro d u e t * W *. I h r each product th e t o t a l amount Incorporated o f tech VCB compound o r m ix tu re . * FMV1193 ADM 006292 (continued) \ ^ T T T ' fcor each p ro d u c t th e name' and a d d re ss o f each so u rce from v h lc h 'y o u r company o b ta in e d each PCB compound o r m ix tu re , and th e am ount^of each PCB compound o r m ix tu re o b ta in e d from each source. d . The name and a d d re ss o f each o f your com pany's f a c i l i t i e s vhlch handle such products (including production f a c ilitie s and w holesale and r e t a i l o u t l e t s ) , end the amount of each product d la trlb u te d through each fa c ility . e . The name and a d d re ss o f aach custom er o f each p ro d u c t, and 11 th e amount o f each p ro d u c t o b ta in e d by each custom er from 11 each f a c i l i t y . For consumer products l i s t only the to ta l i production of aach product a t each f a c ility and the to ta l I number o f c u sto m ers. Do n o t p ro v id e th e name and a d d re ss \ o f each custom er of consumer p ro d u cts. 3 . For eaeh PCB compound o r m ix tu re used by your company i n I t s operations other than fo r Incorporation In to I ts products, fo r each company f a c i l i t y , d u rin g each y ear of 1971, 1972, 1973, 1974, and th e f i r s t two q u a rte rs o f 1975: 0 a . A. d e s c r ip ti o n o f each u s e . b . F or each u se th e t o t a l amount o f aach PCB compound o r m ix tu re. c . For each use th e seme end eddresa of each source from vhlch your company o b ta in e d each PCB compound o r m ix tu re , and th e amount o f aach PCB compound o r m ix tu re o b ta in e d from aach source. 4. X For a ac h FC8 compound o r m ix tu re re c laim ed by your company, f o r each company f a c i l i t y , d u rin g each y ear of 1971, 1972, 1973, 1974, and th e f i r s t two q u a rte rs o f 1975: i* a. A d e sc rip tio n of each m ethod of reclam ation. b . For each method o f reclam atio n , th e t o ta l amount of aac h F8 compound o r m ix tu re re c la im e d . c . The t o t a l amount o f eaeh PCB compound o r m ix tu re re c laim ed . F/wvnM AD* 0 0 6 2 9 3 t 3 d . Thj* name and a d d re s s o f each so u rc e from which your c ra p an y o b ta in e d PCB compounds^ o r m ix tu r e s , and th e a o a u n t o f each PCB compound o r m ix tu re o b ta in e d from : "Tidch so u rce. ~ ' e. For each method of reclam atio n , the lo c a tio n of every re c la m a tio n s i t e , th e name and a d d re ss o f each p a rty In v o lv e d In th e re c la m a tio n o f each PCB compound or m ix tu r e , and th e amount o f each PCB compound o r m ixture reclaim ed by each p a rty . 5. For e ac h PCB compound o r m ix tu re disp o se d o f by your company (w ith or w ithout the Involvement of o th er p a r tie s ) , fo r each Company f a c i l i t y , d u rin g each y e a r o f 1971, 1972, 1973, 1974, and th e f i r s t two q u a r te r s o f 1975: a . A d e s c rip tio n o f each method o f d is p o s a l. b . For each method o f d is p o s a l th e t o t a l amount o f each PCB compound o r m ix tu re d isp o se d . w The t o t a l amount o f each PCB compound o r m ix tu re d is p o se d . d . The name and a d d re ss o f each so u rce from which your company o b ta in e d PCB compounds o r m ix tu re s , and th e amount o f each PCB compound o r m ixture* o b ta in e d from ^ each source A e . For each method o f d is p o s a l, th e lo c a tio n of every d isp o sal I t s , th e neme and ad d raaa o f each p a r ty In v o lv ed In th e d is p o s a l o f each PCB compound o r m ix tu re , and th e amount o f eaeb PCB compound o r m ix tu re d isp o sed o f by each p a r ty . 6 . The c o m p o sitio n by ch em ical name and p e rc e n t b y w eight o f each PCB compound o r m ix tu re j ^ g j u c e , Im p o rted , s o l d , re c la im e d , u sed , a n d /o r. d is p o se d o f by your company s in e s J a n u a r - ^ 1 9 7 ^ . ,^ 7 . The r e s u l t s o f any end e l l sam pling and a n a ly s is perform ed by y e a r company, i t s agents or c o n tra c to rs sin e s January 1, 1971, csacarn ln j the follow ing: a . C o n c e n tra tio n s o f PCB compounds o r m ix tu re s In th e a f f lu e n t 1 o f any d isc h a rg e s by th e company (I n to w aters o f th e U nited S ta te s o r P u b lic ly Owned T reatm ent Worlea) o r in th e am issions o f th e company I n to th e a i r . F ilO U S S ADM 006294 4 . - b . TKp flo w a n d /o r c o m p o sitio n o f any d is c h a rg e s o r em issions ~ b ^ t h e company ( in to w a te rs o f th e U nited S ta te s o r P u b licly OJ&ed T reatm ent W orks, o r i n t o th e a i r ) which c o n ta in PCB 7 -- --compounds o r m ix tu re s . c . C o n c e n tra tio n s o f PCB compounds o r m ix tu re s in re c e iv in g w aters (both upstream and downstream) of any discharges by th e company which c o n ta in PCB compounds o r m ix tu res and c o n c e n tra tio n s o f PCB compounds o r m ix tu re s in th e a i r in th a re a of the company. 8. The methods by which PCB compounds o r m ix tu re s a r e tra n s p o rte d to , by, an d /o r from your company, In clu d in g : a . A d e s c rip tio n of each method o f tra n s p o rta tio n , and th e form in w hich PCB compounds o r m ix tu res a re tr a n s p o rte d by each m ethod. Where d i f f e r e n t methods o f tr a n a ; p o rta tic i! a re used a t d if f e r e n t f a c i l i t i e s sp e c ify which tra n s p o rta tio n method i s used a t each f s c i l i ty . b . The names and a d d re ss e s o f e l l known tr a n s p o r te r s o f PCB compounds o r m ixtures. r> 9. A ll o ccasio n s (In clu d in g s p i l l s ) o f which you e re aware on which / PCB compounds o r m ix tu re s have o r may have been in tro d u c e d in to . the environm ent. In p a rtic u la r, describe such occasions Insofar a s `th e y In v o lv ed PCB compounds o r m ix tu re s l a t h e i r liq u id s t a t e , es incorporated in to closed system s, or as Incorporated in to open sy ste m s. For each occasion in d ic a te neme end ad d ress of p arty involved; d a te s, tim e, and lo catio n of th s discharge or s p i l l ; and tb a amounts involved. 10. A d e sc rip tio n of any adverse h ealth or environm ental e ffa ets w hich you know o r b a lle v e to hava r a s u l t a d from th a in tr o d u c tio n of K compounds o r m ixtures in to th e environm ent. In d ic a te mgp s p e c i f i c o c c a sio n s in c lu d in g d a ta s , tim a s , lo c a t io n s , am ounts, v ' ' a ft f p a s ti e s in v o lv ed fo r which such a f f e c ts a ra known. 44 -- ^ 11 Aaf sad. a l l . o th e r in fo rm a tio n which you p o sse ss co ncerning: i a . Tha p ro d u ctio n , im p o rtatio n , reclam atio n , u se , d is trib u tio n , and d is p o s a l o f PCB compounds o r m ix tu re s . F 0 V W S ADM 0 0 6 2 9 5 b . d is c h a rg e o f FCB compounds o r m ix tu re s I n to th e environm ent. ---w In i d d i t l o n to th e sh o v e , EPA would a p p r e c ia te re c e iv in g any o th e r in fo rm atio n which you possess concerning th e d is tr ib u tio n and discharge o f PCB compounds o r.m ix tu re s by so u rc e s o th e r th a n your company, in c lu d in g your company1s cu sto m ers and s o u rc e s . .\ A i i. t -* r A F0M 197 ADM 0 0 6 2 9 6 Monsanto !L J i M l J. MONSANTO INDUSTRIAL CHEMICALS CO BOO N. Lindbergh Boule vard St. Louis. Missouri C3I65 Phone: 3M; 694-1000 J u n e 6 , lf>73 McGraw E d is o n Power S ystem s D iv . P .0 Box 160 C e n tr a l P la n t 12th & M adison Avenue South M ilwaukee, W isconsin 53172 Gentlemen : As we h ave p r e v io u s l y n o t i f i e d you by way o f c o r r e sp o n d e n c e s in c e e a r ly 1 9 7 0 , th e m a te r ia l d e sc rib ed on th e a tta ch ed acknowledgem ent o f your order co n ta in s p o ly c h lo rin a te d b ip h en y ls (PCB). P o ly c h lo r in a te d b ip h en y ls a r e .h ig h ly s ta b le ch em ical compounds and are not r e a d ily b io d egrad ab le. T h e r e f o r e , when p la c e d in th e en v iro n m en t t h e y may be c o n s id e r e d c o n ta m in a n ts and may a d v e r s e ly a f f e c t some s p e c i e s o f anim al and marine l i f e . You m ust ta k e e v e r y p r e c a u tio n t o p r e v e n t any e n t r y o f poly c h lo rin a te d b ip h en yls in to th e environm ent through s p i l l s , u sage, lea k a g e, d is p o s a l, v a p o riza tio n or otherv.'ise. This m a teria l should not be used by you or your custom er in equipm ent, packaging m a teria ls or products involved in the p ro cessin g , han dling, or storage o f food , food rela ted p ro d u cts, anim al fe e d s , food wrapping or co n ta in er m aterials^ potable w aters or pharm aceuticals. Very tr u ly you rs, /jk Attachm ent Howard S. B erg en , r . ' D irector S p e c ia lt y P ro d u cts Group unit of Monsanto Company F00118 ME 00024 O Monsanto MowiAirro mourntm cmcwicals co. 00 N.UnHr|A loultvtr S t. toult, Mlaiovri 831B8 P**Mi QI4J I4-1000 Ju ly 13, 1973 Dr. Martha Sager, Chairman E fflu e n t Standards and Water Quality Inform ation Advisory Committee E nvironm ental P r o t e c t io n Agency Room 821, C r y s t a l M a l l , B u i l d i n g 2 Washington, D.C. 20460 > Re: E fflu en t Standards and Water Q uality Inform ation Advisory Committee Agenda and Notice o f Public Hearings Federal R e g i s t e r , Vol. 38, No. 116, Page 11868 Monday, June 10, 1973 Dear Dr. Sager: Monsanto Company, as an i n t e r e s t e d p a r t y and a m a n u fa c tu re r o f p o ly c h lo rin a te d biphenyl (PCS), would lik e to take t h i s o p p o rtu n ity to share with the Committee, and presen t for the record, our experiences regarding the manufacture, s a l e and h a n d l i n g o f FOB and I t s r e l a t i o n s h i p to the environment. 'W'tvflpe ~tfil-tf-'inf6rmaTT6t f r - i i^rlg-'w ith `th ^ 'a fta rc h e d v*xirfbf t s y w i l l be h e lp f u l to the Committee and the Adm inistrator * when p roposing e f f l u e n t standards f o r to x ic p o l lu t a n ts . BACKGROUND Monsanto Company h a s been a m ajor m a n u f a c t u r e r o f c he m ic a l p ro d u cts sin c e 1901. These products a re used in numerous American in d u s t r ie s , and in f a c t, through our research d e p a r t m e n t , we h a v e p l a y e d a r o l e i n d e v e l o p i n g new p r o ducts to meet the needs of Industry and the consumer. On some o c c a s i o n s a c h e m ic a l compound w i t h s p e c i f i c p r o p e r t i e s is developed to meet a need in a c e rta in a p p lic a t i o n . In o t h e r c a se s a chemical compound with unique p ro p e rtie s is developed f i r s t -- possibly through innova t i v e r e s e a rc h o r even by happenstance - - and then an end- use Is found it * WMHMI Cimiaif K M V I199 ACM CC236 14S Dr. Martha' Sager July 13, 1973 Page 2 She c h e m i c a l s t r u c t u r e o f PCB h a s b e e n known f o r n e a r l y 100 y e a r s . I t was n o t u n t i l the l a t e 1920s th a t a use f o r PCB was f o u n d -- a s a d i e l e c t r i c f l u i d i n t r a n s f o r m e r s a n d c a p a c i t o r s , The p r o p e r t i e s o f PCB - - i n e r t n e s s f i r e r e s i s t a n c e and a non c o n d u cto r o f e l e c t r i c i t y - - seemed to be p e rfe c tly suited to these e le c t r i c a l applications where high-voltage arcing could occur, possibly resulting i n s e r i o u s f i r e s o r damage to the equipment. Monsanto b e g a n c o m m e r c ia l p r o d u c t i o n o f PCB i n 1929. As t h e u n i q u e p r o p e r t i e s o f t h e m a t e r i a l became known new uses were found. For example, th e ir f i r e - r e s is t a n t nature made them e x c e l l e n t c h o ic e s f o r use i n h e a t - t r a n s f e r f l u i d s Their in e rtn e ss gave lo n g -la stin g q u a litie s to lu b ric a n ts. T heir use in surface coatings improved waterproofing characteristics. Handling of the product at the manufacturing level has n o t p resen te d problems so long as the p ro p er i n d u s tr ia l h y g i e n e p r a c t i c e s were f o l l o w e d and PCB h a s always b een c o n s i d e r e d l e s s h a z a r d o u s t h a n many o t h e r c h e m i c a l s i n everyday use. T h e r e f o r e , i t a p p e a r e d t h a t PCBs were a v e r y s u i t a b l e product which met the needs of In d u stry , Late in the 1960s, sophisticated an aly tical procedures were developed which could detect very minute qu an tities >'0*f--PCB Irtf^narbere-.'1*-'F o l'l-b w -tr^ 'th is"' *br ea k t h rc '* r e s e a r c h e r s d i s c o v e r e d t h a t PCB c o u l d p o s s i b l y be a f f e c t i n g c e r t a i n forms o f a q u a tic , marine, t e r r e s t r i a l and avian w ildlife. The p e r s i s t e n t n a t u r e and s t a b i l i t y o f PCB, w h i l e so d e s i r a b l e from t h e s t a n d p o i n t o f many i n d u s t r i a l a p p l i c a t i o n s appeared to be undesirable in terms of our environment. INDUSTRY ACTIONS When q u e s t i o n s a b o u t t h e e f f e c t o f PCB on t h e e n v iro n m en t f i r s t s u r f a c e d , Monsanto Company r e v i e w e d i t s p r o d u c t l i n e a n d t h e a p p l i c a t i o n s f o r t h e s e p r o d u c t s . As m o re 'd a t a were developed and the environmental controversy grew, Monsanto t o o k s t e p s i n t e n d e d to r e d u c e t h e e n t r y o f PCB i n t o th e e n v ir o n m e n t. The company s to p p e d the s a l e o f PCB f o r u s e i n v a r i o u s a p p l i c a t i o n s , e x c e p t where no F,ftfl1200a c c e p ta b le a l t e r n a t i v e s were a v a ila b le . AO oc 149 Dr. Martha Sager July 13, 1973 Page 3 Today, PCB m anu factu red by M onsanto' Company la so ld to th e e le c t r ic a l in d u stry where i t is used in clo sed system s a s a d i e l e c t r i c f l u i d in tran sform ers and c a p a c ito r s - a p p l i c a t i o n s f o r which we un d erstan d th e r e co n tin u e to be no a c c e p t a b le s u b s t i t u t e s . Our m a n u fa ctu rin g and s a l e s r e d u c tio n program was a u n i l a t e r a l a c t i o n tak en by Monsanto and was based on our e v a lu a tio n o f developing environm ental data. R ecognizing the need for proper co n tro ls in the handling and u se o f FCBs, r e p r e s e n ta tiv e s o f the transform er and c a p a c ito r in d u s tr ie s , u t i l i t i e s , and governm ental a g en cies under the i n i t i a l auspices o f the N ational E lec trica l M anufacturers A s so c ia tio n formed American N ational Standards I n s t it u t e Committee C -107. A copy o f the Committee's r e c e n t l y is s u e d p roposed g u id e lin e s f o r th e h a n d lin g andd isp o sa l o f d ie le c t r ic flu id s i s attach ed . These1g u id e lin e s r e f le c t the in d u stry 's understanding o f the need fo r proper c o n tr o l and should c o n trib u te s ig n if ic a n t ly toward th is o b je c tiv e . TOXICITY IN PERSPECTIVE In S e c tio n 502 ( l 3) o f the cu rren t F ederal Water P o llu tio n C ontrol A ct, the term " toxic p o llu ta n t" is defined as "those p o llu ta n ts or combinations o f p o llu ta n ts including d i s e a s e c a u sin g a g e n t s , which a f t e r d is c h a r g e o r upon exp osu re, in g e s tio n , in h a la tio n or a s s im ila tio n in to any o rg anI zmj^e"1th"e'r'cfl r ec t f / " Fran**We"'en g ird himen't or i n d i r e c t l y by in g e s tio n through food chains w i l l, on the b a sis o f in form ation a v a ila b le to the A dm inistrator, cause death, d is e a s e , b e h a v io r a l a b n o r m a litie s, ca n cer, g e n e tic muta i nt i o n s , p h y s i o l o g ic a l m a lfu n c tio n s (in c lu d in g , m a lfu n ctio n s rep rod u ction ) or p h y sica l deform ations in such organisms or th eir offsp rin g." W hile the breadth o f th is d e fin itio n can be so construed as to p e r m it th e i n c lu s i o n o f many su b sta n c e s on a l i s t o f " t o x ic p o l l u t a n t ( s ) , " we concur w ith the r e c e n t s u g g e s tio n o f the EPA's A ctin g A dm inistrator (F ederal R eg ister V ol. 33, No. 129, page lSO^ii) that Congress intended the A dm inistrator under the Act " . . . to be s e le c t iv e in determ ining which o f the p o t e n t i a l l y la r g e number o f c a n d id a te su b sta n ces Au'rt CCc 2SC Font201 150 Dr, Martha Sager July 13, 1973 Page 4 a c tu a lly sh ou ld be l i s t e d a t variou s tin e s ," Although n o t s p e l l e d o u t In th e d e f i n i t i o n , we f e e l i t in p orcan - to consid er the degree o f to x ic ity o f the substance- * d i f f e r e n c e s in b i o l o g i c a l s p e c ie s * s e n s i t i v i t y ; 'and* w h eth er o r n o t th e su b s ta n c e p o se s a th r e a t to man, anim als b ir d s , th e a q u a tic environm ent or some o th e r a sp ect o f * the ecosystem , Por example, th ere i s a m aterial d iffe r e n c e between the t h r e a t to human h e a lt h p osed by equal amounts o f the "cyanide ion" and "PCBs," both o f which su b sta n ces appear on your p rop osed 1 -lst o f p o l l u t a n t s . We f e e l c e r t a in th e members o f you r com m ittee w i l l a g r ee th a t th e se two s u b s ta n c e s sh o u ld n o t be c o n sid e r e d on th e same b a s is m erely because they are both suggested fo r in c lu sio n in th e same l i s t . We t r u s t th a t com p arative d if f e r e n c e s in th e p o t e n t ia l hazard to h e a lth and our environment o f the variou s sub sta n ces proposed for your l i s t w ill be an important fa c to r in your d e lib e r a tio n s and d eterm in a tio n s. On th e b a s i s o f a v a i la b l e e v id e n c e , i t would appear th a t PCBs p ose l e s s o f an a c u te t o x ic h e a lth hazard than many su bstances not proposed for your l i s t , and a t the le v e ls found in the t o t a l environment are not a th reat to p u b lic h e a l t h . We b e l i e v e th e s e view s agree w ith the c o n c lu s io n s r ea ch ed by th e In ter d e p a r tm en ta l Task F orce on PCBs in I t3 r e p o r t d ated May, 1972 (CCM-72-1CUI19). We s i n c e r e l y b e l i e v e , b eca u se o f M onsan to's s a l e s p o l i c i e s d isc u sse d elsew h ere, and a c tio n s o f o th e r s throughout the w o r ld , th a t th e l e v e l s o f FC3 in th e a q u a tic environm ent a r e even lo w e r now than a t th e tim e th e Task Force r e p o r t waa p rep a red . BIODEGRADATION A v a lid assessm en t o f the environm ental impact o f p o ly c h lo r in a te d b ip h en yls must in clu d e co n sid era tio n o f the p e r siste n c e o f these m a teria ls. C ertain reports have been made th a t PCBs a r e n o n -d e g ra d a b le . However, alth ou gh much work rem ains to be done, an a n a ly s is o f a v a ila b le in fo r m a tio n and in fo r m a tio n from s t u d ie s by Monsanto in d ic a t e beyond any r e a so n a b le doubt th a t the many FCB V flm 151 Dr. Martha Sager July 13,-1973 Page 5 Isomers degrade In the environment a t d iffe r e n t rates T his Inform ation In d ica tes that under the proper condi t i o n s o f u se and c o n t r o l , some o f the commercial PCEs w hich a re m ix tu r e s o f s e v e r a l iso m e r s, can be u t i l i z e d and th e ir s a f e t y b e n e fits can be r e a liz e d w ithout serio u s adverse consequences to the environment. In May, 1972 we sh ared w ith members o f the Federal I n t e r d ep artm en tal -Task Force on FC3s the r e s u l t s o f s t u d ie s o f r e s id u a l FCBs in anim al t i s s u e s and b io d eg r a d a tio n by a ctiv a ted slu d g es. A copy o f th is p resen tation Is attached fo r review by your Committee. A r tic le s describ in g in more d e t a il the r e s u lt s o f the degradation stu d ie s in a c tiv a te d slu d g e s and s o i l s are being prepared fo r p u b li c a tio n , Copies o f th ese rep orts w ill be m ailed to your Corrcnlttee when th ey are com p leted. EFFLUENT STANDARDS The w orldw ide i n t e r e s t in FCBs and t h e ir environ m en tal impact has r e s u lte d in an abundance o f published a r t i c l e s . To a s s i s t th e Committee we have a tta c h e d a b ib lio g r a p h y o f some o f the p e r t in e n t l i t e r a t u r e , c o p ie s o f s e le c t e d a r t i c l e s and a copy o f the In terd ep artm en tal Task Force r ep o rt. T his r e p o r t, in our o p in ion , is an e x c e lle n t r e fe r e n c e document and we recommend i t to the Committee as a valuable source o f inform ation as you consider p o ssib le efflu en t standards. A lthough much h as been p u b lis h e d , much more s c i e n t i f i c in fo r m a tio n i s r e q u ir e d . T h is c r i t i c a l need fo r more know ledge was r e c o g n iz e d by the Task Force and i s h ig h lig h t e d in i t s r e p o r t under " F in d in gs, C on clusions and R ecom m en d ation s" . I t i s our con sid ered o p in io n that In the absence o f c r i t ic a l b a s ic s c i e n t i f i c data any attem p t to e s t a b l i s h a FC3 s t a n d a rd fo r w a ter e f f l u e n t s a t p o in t so u r c e s would be p r e mature a t th is tim e. Pending the a v a i l a b i l i t y o f the data which would c o n tr ib u te to the establishm ent o f a r e a lis t ic e fflu e n t standard, i t is appropriate to consider that the r estr ic te d use and p rop er c o n tr o l o f PCBs have and w i l l co n tin u e to r e s u lt in a dim inished impact on the environment. F urther *,more, th e r e c e n t r u lin g by the Food and Drug A d m in istra tio n 001203 1 S 2 ad ^ CG235 Dr. Martha Sager July 13, 1973 Page 6 ( F e d e r a l R e g i s t e r , Volume 3 8 j Number 129, J u l y 6, 1973) p r o v i d e s f o r t e m p o r a r y PCB t o l e r a n c e s i n f o o d , animal, feeds and food packaging m a te ria ls, thereby lim iting exposure to humans and dom estic anim als. We a p p r e c i a t e t h e o p p o r t u n i t y t h e Committee h a s p r o v i d e d f o r i n t e r e s t e d p a r t i e s to c o n tr ib u te inform ation. I f you have any q u e s tio n s concerning our comments o r any o f the a t t a c h m e n t s we w i l l be p l e a s e d to s u p p l y f u r t h e r e x p l a n a tio n s o r inform ation upon re q u e st. R espectfully submitted, WBP/bt Enclosures W, B. F a p a g e o r g e Manager Product Acceptability C. z' " ^ io n i904 ACM CC2 2 93 153 o .. MINUTES OP MEETING ON PROPOSED PCB EFFLUENT STANDARDS February 28, 197^ Monsanto Company St. Louis, Mo. ..M E X H IB IT S ACM 07 76 inm ?m 154 r^. Chairmani Kr. V. B. Papageorge Manager, Product Acceptability Monsanto Industrial Chemicals Co. Objective: The purpose of the meeting was to share Information, experiences and Impressions to help each of the participating companies in taking appropriate actions which are mutually supportive and effective In persuading the Administration of EPA to modify the proposed PCB Effluent Standard. r AJM 07277 Him T06 155 PARTICIPANTS PCB STANDARES MEETING February 28. 1974 CERTIFIED BALLAST MANUFACTURERS Mr. N. R. Clark Universal Manufacturing Co E.I.A Mr. Arnold S. Doty Dr. E. M. Moore Mr. Rudy Carlson P. R. Mallory ft Co., Inc Electrical Utilities Co. Electrical Utilities Co. GENERAL ELECTRIC COMPANY Mr. James S. Nelson Mr. Stuart Rlchel Dr. Edward L. Simons JARD COMPANY, INC. Mr. Richard Rollins * NATIONAL E1ECTRICAL MANUFACTURERS ASSOCIATION (NEMA) Mr. A. H. Salazar WESTINGHOUSE CORPORATION Mr. H. Sheppard Mr. N. H. Smith A* 00 7 7d 156 MONSANTO COMPANY P. 0. Benignus H. S. Bergen D. B. Hosmer R* H. Munch V. B. Papageorge V. V. Withers C. Paton V. R. Richard J. R. Savage E. S. Tucker P. L. Wright Market Manager Business Director Utilities and Environmental Protection Director Senior Science Fellow Manager, Product Acceptability Attorney Product Manager Manager, Research and Development Manager, Manufacturing Research Group Leader Manager, Toxicology ADM 007279 lorn ?08 157 AGENDA PCB EFFLUENT STANDARDS MEETINQ February 28, 1974 9 : 0 0 AK 1. Welcome - H. S. Bergen 9 : 1 0 AK 2. Introductory Remarks - V, B. Papageorge a. Brief Review of Proposed Standard b. Critical Action Dates c. Objectives of Meeting 9:15 AM 9:45 AM 10:15 AM 10:30 AM 11:30 AM 12:00 Noon 12:30 PM 1:15 PM 2:00 PM 2i*5 PM 3:00 PM 3:30 PM 4:00 PM 3, Discussion Topics a FCB Characteristics - Realistic Definition chemical, physical, biodegradation b. Sampling and Analytical Methodology Break c Toxicity Acute Chronic d. Bloaccumulatlon - Blomagnlflcatlon e. Dilution - Stream Size Lunch f. Proposed Effluent Standard g. Control at Manufacturing and Use Sites Current losses Background Break h. Economic Considerations l. Action Plans Adjourn AOM 00 7 Foni?09 158 A* MINUTE^ OP PCB EPPLPENT STANDARDS MEETING 1. Mr. Howard S. Bergen, Jr., Director, Specialty Products Business Group of Monsanto Industrial Chemicals Company, welcomed the participants. 2. Introduction - V. B. Papageorge Mr. Papageorge summarized the timetable past and future on toxic pollutants: July 6, 1973 - Toxic Pollutants list published September 7 $ 1973 - Pinal toxic pollutants list pub lished Including PCBs and 8 other chemical classes (e.g. cyanide, mercury, DDT, cadmium, etc.) December 27, 1973 - Proposed Effluent Standards published January 18, 197* - Piling date for status as participant at proposed EPA Hear ing on Standards r" January 25, 197* - (i) Prehearing Conference with EPA (ll)* NEKA, Monsanto, O.E. and Vestlnghouse recognized as participants. (ill) A total of 38 objectors ex pressed an Interest. They represented Industry or trade associations with the exception of the Michigan Water Research Commission and two powerful environmental groups (Environmental Defense Pund and National Resources Defense Council). (lv) Presiding officer made It clear that Hearings will be strictly for cross-examination o f participants,1, testimonies in affidavit form only. AN A 007 Zes1 Fornaio 159 -2- March 15, 1974 April 8, 1974 Written testimony by ^8 objectors to~be submitted in affidavit formT Hearings open for cross-examination and rebuttal evidence. CN"/Cd/Hg first three. PCBa are 7th (third from last). Mid-May, 1974 Hearings completed. (Evenings/weem ends may be used.) June 25, 1974 71nal standards published - effective In one year. It should be noted that others who are affected by these standards can still comment by March 25 to: Dr. C. Hugh Thompson, Chairman-Hazardous and Toxic Substances Regulation Task Force Office of Water Protection Agency, Environmental Protection Agency Washington D. C. 20460 Industry representatives still wishing to comment and who need r more background Information can contact any of the Industry participants (see attached list) or Mr. W. B. Papageorge of Monsanto (314-694-4051). Mr. Rlchel (O.E.)i (i) Made a plea for greater Industry participation. Comments can still be made up to March 25 with sound excuse for tardiness. (il) EPA at January 25 prehearing Conference were reluctant to expose themselves to cross-examination* Dr. Hugh Thompson to be available for cross-examination at Hearings. (ill) Many objectors had common Interest (e.g. environmentalists). EPA suggested a common counsel for this group. (lv> On each of first 3 pollutants, EPA would offer 2 witnesses. Mr. Doty (P.R, Mallory) asked about bearing of economic factors on standards. Mr. Rlchel (O.E.) stated: (l) Law Is clear-economic factors are not relevant In establishing standards. (ll) EPA Is somewhat of a split personality on this. The Fomni ADM 007232 160 -3- F resid ln g O ffic e r at the Prehearing Conference ruled that econ om ics a r e ' r e le v a n t . NRDC (N a tio n a l R esou rces D efense C o u n cil) o b je c te d and was o v e r -r u le d . (ill) In d u stry can and should th erefo re Introduce relevan t econom ic d a ta . EPA would be w ise not to e x p r e s s ly r e f e r t o such data In th e p u b lish ed standard o th e r w ise NRDC c o u ld go t o c o u r t and EPA o v e r -r u le d . Department o f Commerce I t was p o in te d put th a t S id n ey R. O a llle r , Deputy A s s is ta n t S ecreta ry fo r Environm ental A ffa irs at the Department of Commerce w rote Monsanto on January 15 a sk in g t h e i r view s on th e proposed e f f lu e n t sta n d a rd s. Copies o f Dr. O a llie r 's l e t t e r and M onsanto's response were c ir cu la te d a t the m eeting. Industry sh ou ld c o n ta c t th e D ep t, o f Commerce. T h e ir l e g a l co u n sel (Mr. Norland) has been a c tiv e on th e s id e o f in d u str y In o th er environm ental h earin gs. Mr. S a la z a r (MEMA) p o in te d out th a t th e PCB Task Porce had recommended a stan d ard f o r PCBs o f 0 .0 1 ppb In th e main body o f w a te r . (EPA was a member o f th a t ta sk f o r c e ) . ANSI C-119 p roposes to u se t h i s Task Porce recommendation and p r in t t h is as a stan dard o f 0 . 0 1 ppb In main body o f w a ter. Mr. Sheppard (V e stln g h o u a e ) q u eried i f p la n t e f f l u e n t standards c o u ld be s e t to meet 0 . 0 1 ppb Dr. Simona (O .E .) s a id t h i s Im plied an a ccep ta n ce o f ANSI C-119 by Industry. There seemed t o be aome doubt on t h i s . , PCB C h a r a c t e r is t ic s Dr. Tucker (Monsanto) presented hand-outs on: ' (a ) M onsanto's proposed d e f i n i t io n o f PCBs (b ) Comments on EPA'a proposed a n a ly t ic a l m ethodology ( c ) M onsanto's p r e -p u b lic a tio n paper on b io d e g r a d a tio n o f PCBs. ( a ) D e f in i t io n o f PCBs 1 -4 c h lo r o b lp h e n y ls do not have lo n g r e sid e n c e tim e. PCBs up t o te tr a c h lo r o b lp h e n y l are not o f concern on environm ental p ersisten ce or blom agnlflcatlon. Dr. Tucker proposed the follow in g d e fin itio n : u v AOH 161 -4- r'- " P o ly c h lo r in a te d b ip h e n y ls (PCBs) se a n s m aterials containing the biphenyl group Which i s c h lo r in a te d and which have been shown to p e r s is t and r a p id ly bioaccum ulate in the aquatic environm ent. These chlorin ated biphenyls are Id en tified as th ose components having gas chromatographic reten tio n tim es greater than 54, r e la tiv e to p , p-DEE s 100, under th e stan dard con d i t i o n s recommended In th e EPA PCB t e s t method." Mr. Sheppard (V e stln g h o u s e ) s a id M onsanto's proposed d e f i n i t io n was r e le v a n t to p e r s is te n c e but was i t r e le v a n t fo r standards d ir e c te d toward to x ic m aterials? Are p e r s is te n t m aterials non toxic? Mr. V r lg h t (M onsanto) s t a t e d th e proposed e f f l u e n t standard had two p a r ts: ( l ) acute lim its d irected to to x ic ity o f material's and s p e c i f i c a l l y l i m i t s PCB c o n c e n tr a tio n s on that b a sis. ( l l ) d a lly load In e fflu e n t - based s o le ly on b io m agnification (relevant to p ersisten ce). Dr. Simons (Q .E .) p o in te d out th a t s e c t io n 3 0 7 -A o f th e proposed stan dard r e r e r s to p e r s is te n c e as b ein g a c r i t i c a l fa c to r to be c o n sid er ed . Dr, T ucker (M onsanto) s t a t e d we were b ad ly h u rt i f a l l PCBs are regarded as p e r s is te n t and i f b io m a g n ifica tio n fa c to r s o f 2 0 0 ,0 0 0 are u sed . R esearchers o th er than Monsanto have found b a c t e r i a l d eg ra d a tio n o f PCBs and th a t PCBs have been found to undergo m etabolism In both a v la r la n and mammalian a n im a ls. Mr. K elson (Q .E .) asked i f proposed PCB d e f i n i t i o n would exclude Aroclor 1016. Dr. Tucker (M onsanto) A roclor 1016 would be exclud ed f o r th e most p a r t I 909% I s low er than p e n ta c h lo r o b ip h e n y l). A roclor 1242 would be exclud ed to 65$ or b e t t e r . A roclor 1254 however would not be excluded. Mr. Papageorge (Monsanto) pointed out that of the factors listed as being critical in determining which pollutants made the EPA list of 9/7/73 only biomagnlflcatlon appeared relevant to PCBs. Dr. Simons (O .E .) agreed. E 001?13 ADM 00723* 162 Hr. W right (M onsanto) sta te d th a t an acute to x ic o lo g ic a l le v e l la d e fin e d in th e EPA B aals ft Purpose document aa ^ 10 ppm (9 6 hour L C -5 0 ). He a ls o b e lie v e s th a t d if f e r e n c e s in t o x i c i t y among PCBs are m inor u n t i l c h lo r in a te d aa h ig h aa A roclor 1 2 6 0 . Hr, N elson (O .E .) a ta ted th a t words should be used in a d is course on d e f in it io n to properly screen us on acute to x ic ity '. In r e fe r e n c e t o a comment th a t A ro clo r 1254 would n ot be exclud ed by th e proposed d e fin itio n . Dr. Tucker (Monsanto) o ffe r e d th e op in ion th a t transform er flu id s were e a sie r to r e cover than capacitors* (b) A n a ly tic a l Methodology Dr. Tucker (M onsanto) s t a t e d th e EPA's proposed method f o r PCB a n a ly s is was b e in g su b m itted to ASTM. He thou ght th e method was w e ll w r itte n and capable o f d e te c tio n to ppt (p arts per t r i l l i o n ) but I t was u n tried and th e q u a n tita tiv e accuracy i s In q u estio n * The method was not subm itted f o r round-robin t e s t i n g b e fo r e EPA adopted I t . Monsanto has found th a t by s p ik in g d i s t i l l e d w a ter w ith 5 0 0 ,0 0 0 ppt or 500 ppb o f PCBs we g e t v a lu e s Tor PCB th a t vary by 555*. TCie EPA, however, cla im s a c a p a b i l i t y o f d e t e c t in g a b so lu te v a lu e s a t 50 p p t. The EPA method Ignores In te r fe r in g su b stan ces. Mr. C lark (U n iv e r s a l M anufacturing) s a id th a t w ith a proposed upper lim it fo r >dB discharge or 5.0648 lb ./d a y the s e n s itiv ity o f th e a n a ly t ic a l method would vary " a ll over th e lo t" depending on th e s i z e o f th e w ater " reserv o ir" in to which th e PCBs d i s charge. Mr. Sheppard (V e stln g h o u se ) commented th a t I f th e a n a ly t ic a l te c h n iq u e s on d eterm in in g PCB l e v e l s are so d i f f i c u l t , how v a lid are th e d e te r m in a tio n o f t o x ic v a lu e s f o r PCBs. Mr. C lark (U n iv e r s a l M anufacturing) asked i f a n a ly t ic a l tech n iq u es d if f e r e n t ia t e between d iffe r e n t ch lorin e le v e ls . Dr. Tucker (M onsanto) s a id i t would depend on th e PCB mixture*! A roclor 1242 cou ld probably be id e n tifie d q u a n tita tiv e ly in a mixture w ith A roclor 1260 but a d d ition o f A roclor 1254 to the mixture would p r e v e n t i d e n t i f i c a t i o n because A roclor 1254 co n ta in s PCB hom ologs th a t o v erla p both A roclor 1242 and 1260. Dr* Munch (M onsanto) s a id th a t th e proposed EPA method does not use high r e s o lu tio n and hence handicaps id e n t if ic a t io n o f individual peaks. Dr. Simons (O .E .) m entioned th a t a f t e r EPA s e t autom otive e m is sio n sta n d a rd s (NXOX) th e a n a ly t ic a l m ethodology was found f a u l t y and th e sta n d a rd s were d e la y e d . In t h i s c a s e , EPA i s not s e t t in g the e fflu e n t standard on a n a ly tic a l methodology but E001214 oOl 163 -6- j on f a c t o r s such as t o x i c i t y and p e r s is t e n c e . The methodology i s r e le v a n t in enforcem ent and m onitoring. This then lead s to th e p o s s ib le argument th a t th e e f f lu e n t standard la c o r r e c t and J u s tifie d on the b a sis o f to x ico lo g y e t a l# but Is not enforceable due to la c k o f an a ccu ra te method fo r a b so lu te valu e d e te r m in a tio n o f PCB d is c h a r g e . Mr. R lc h e l ( O .E .) p o in te d out th a t EPA w on't buy an answer to th a t argument which seek s to r a is e th e e fflu e n t standard to a l e v e l t h a t can be a c c u r a te ly m easured. Mr, Savage (Monsanto) f e l t s tr o n g ly , however, th a t t h is dilemma needed to be In the record. Others agreed. Dr, Tucker (M onsanto) s a id ASTM would h old a round-robin on th e EPa method and th a t- Monsanto would p a r t i c i p a t e . He w i l l send th e name o f th e ASTM c o n ta c t to th e p a r tic ip a n ts so th a t th ey can d ecid e I f th ey want to Join the round-robin t e s t . Mr, Sheppard (W estln gh ou se) s a id he was not prepared to a c ce p t t^iat th e proposed EfS method f o r d eterm in in g q u a n t it ie s and ty p e s o f PCB In sam ples and anim als was a ccu ra te enough so th a t t o x ic l i m i t s c o u ld be d e fin e d on th e b a s is o f PCB l e v e l s o f q u e s t io n able accuracy. T oxicity Mr. Hosmer (M onsanto) s t a t e d th a t th e o r ig in a l EPA p u b lic a tio n on Water Q u a lity C r it e r ia came from a p u b lic a tio n by McKee and V o lfe f o r th e S ta te o f C a lif o r n ia . The McKee/Volfe volume was w e ll done and EPA d id n ot change much o f I t . There Is now a new 2-volum e EPA e d i t io n e x tr a c te d from th e work o f 10 com m ittees o f th e N a tio n a l Academy o f S c ie n c e s . The t o x i c i t y o f PCBs I s r e la t e d to salmon egg s tu d ie s and Monsanto doubts the v a l i d i t y o f t h i s . Monsanto has made t h e i r f e e l i n g s known t o Dr. Thompson o f EPA but he thought th e c r it e r ia were sound. Since then R u ssell Train'has been sued by NRDC and o th e r groups on th e grounds th a t th e to x ic p o llu t a n t s l i s t la not lon g enough and th e proposed standards are to o le n ien t Mr. W right (M onsanto) went through th e r a tio n a le used by EPA in a r r iv in g a t a PdB d isc h a r g e maximum o f 0.0 6 4 8 lb ./d a y . He a ls o showed how th e stan dard cou ld be changed and y e t be c o n s is t e n t w ith p u b lish e d d ata on PCBs. D e t a ils f o llo w . (a ) PDA s e t a r b r lta r y proposed to le r a n c e s : 5 ppm in f i s h f o r human consum ption 5 ppm In components f o r anim al fe e d 0 . 5 ppm in com plete anim al fe e d V K nm ?.i5 0O1 *' 164 -7- (b) Monsanto would not disagree with these tolerances. (c) PDA has presented - acute toxicity H a l t s (point sources) - chronic toxicity H a l t s (dally load) Acute toxicity H a l t s : 96 hour LC-50 studies for PCBa show: ~ 2 8 0 ppb In fresh water (bluegill) ~ 1 0 ppb In coastal or seawater (pink shrinp/oysters) Published data based on aaterlals leaving an outlet and going Into a body of water. Acute H a l t s have no direct relation to chronic Halts. Chronic toxicity Halts: The EFA equation Is: Chronic H a l t X water flow rate X safety factor ga/day discharge In Karine organises the chronic H a l t la set as jsfj 0-0167 ppb In fresh water the chronic H a l t has been deteralned by using 0.5 ppm as toxic limit for salmon eggs and a 200,000 blonagnlfleatlon factor. This gives a chronic H a l t of IoE,O C O s 9 -jyg L.P p b The blomagnlflcatlon level of 2 0 0 ,0 0 0 la based on unpublished data from Stalling ft Never (Pish Pesticide Lab, U. S. Dept, of Interior, Colombia, Mo.). Dr. Simons Said that In response to repeated requests by O.S. to the Columbia Lab the only reference they have been given is .a Stalling ft Keyer paper presented In Carolina In 1971 and which contains no mention of a 2 0 0 , 0 0 0 factor. Mr. Wright (Monsanto) stated he has seen only one literature reference to an accumulation factor of -- 200,000 and that was In e hepato pancreas of a pink ahrlap. If the PCB level was calculated on the basis of the total ahrlap then the accumulation factor was only 22 ,o otf . Other references give accumulation factors of 1000-75*000 for whole tissues of various fresh water organisms. Accordingly. Mr. Bright proposes that a blomagnlflcatlon factor or 30.000 and not~2o0 . o w oe used, ^ae also proposes that we retain the chronic H a l t of 0*5 PPP with^ out debating the salmon egg issue. : AD H 007287 1001216 165 T h is would le a d t o a d isc h a r g e l e v e l f o r PCBs: 0-5 30 ,0 0 0 X, 10,000 x (flow rate) 0.5 . X (safety factor) 5.4 (c o n v e r sio n into lb ./ day) O .459 lb ./day This compares to the proposed standard o f 0.0646 lb ./d a y . The s a f e t y f a c t o r comes from th e EFA's B a sis and Purpose document supporting the proposed e fflu e n t standards, i t is supposed to ta k e a cco u n t o f n o n -p o in t so u rc es o f PCBa and i s the same as 6 o f th e 9 t o x i c p o llu t a n t s proposed f o r EPA sta n d a r d s. M onsanto's M edical Department, f e e l s t h i s s a f e t y f a c to r la a r b itr a r y and c o n fer s no r e a l t o x ic o lo g ic a l b e n e f it . I f d e le te d , the r ev ise d Wright PCB d isc h a r g e l e v e l would be 0 .9 1 8 lb ./d a y . One o f th e most c r i t i c a l p a r ts o f th e d isch a rg e eq u a tio n i s th e w ater flo w r a t e 7 A s i g n i f i c a n t number o f d i e l e c t r i c PCB m anufacturers have p la n ts on r iv e r s where th e flow ra te i s under 100 c f s o r 1% o f th e EPA c u t - o f f flo w o f 1 0 ,0 0 0 c f s . S ev era l p la n ts d isch arge in to sewage p lan ts which in turn have tr e a te d liq u id flow in g in to r iv e r s or streams w ith very low flo w r a t e s . Por a r iv e r w ith 100 c f s flow th e EPA maximum disch arge would drop to 0.000648 lb ./d a y or 0 ,1 6 2 lb ., in a 250 work-day y e a r . Even a r e v ise d standard o f 0 .9 1 0 lb ./d a y a t 16,000 c f s would o n ly be 0 .0 0 9 1 8 lb ./d a y at 10 0 c fs or ^ / 2 . 3 lb . per 250 work-day year. C learly th is Is a staggerin g ta rg et to nave .to m eet. Mr. Doty (M a llo r y ) p o in te d out th a t in th e p r e se n t language o f th e EPA stan d ard s m un icip al sewage system s are n ot con sid ered point sou rces. Mr. R lc h e l (O .E .) was o f th e o p in io n th a t where a p la n t d i s charged in to a sewage system w ithou t treatm ent and hence in to n a v ig a b le w aters th e p la n t co u ld have to comply* w ith e f f lu e n t stan d ard s on t o x ic p o l l u t a n t s . Mr. Fapageorge (Monsanto) f e l t we sh ou ld n o t be com placent and regard d isch a rg e to sewage p la n ts b e in g th e answer to problem s. Mr. Hosmer (M onsanto) s t a t e d t h a t 1 0 , 0 0 0 c f s r e p r e se n ts th e la r g e s t flo w th e PA w i l l c o n s id e r on th e grounds th a t a l l In d u stry would move t o th e la r g e s t r i v e r . The o p p o s ite o f th a t argument i s th a t i t encourages sm all p la n ts on every stream in the country. Mr. Sheppard (W estln gh ou se) r a is e d th e is s u e o f se d im e n ta tio n . Since i t appears th at a l l the experiments to e sta b lish to x ic values were run w ithout sediment e ffe c ts being considered, the r e a l - l i f e v a lu e s were q u e s tio n e d . PCBs a tta ch th em selves to sed im en t. Furthermore th e sedim ent moves down r iv e r and so PCB would be d isp e r se d from the p o in t sou rce. I t was p oin ted out by Dr. Richard (Monsanto) th a t A roclor 125^ i s so lu b le in water up to 3 6 ppb ana th a t m tim e p a r titio n in g between sedim ent and Foni? i7 ADM 0 0 7 2 6 a 166 -9- w ater c o u ld ta k e p la c e* Mr* W right (Monsanto) agreed th a t the d isch a rg e lim it s mere extrem e c a ses In the absence o f sediment c o n s id e r a tio n s and t h i s was worth stu d y and In co rp o ra tio n Into argumenta agaln at the proposed l e v e ls . Dr. Simona (0 * B .) q u er ied w hether we were c o r r e c t In concen t r a t i n g our a tta c k s on th e c r i t e r i o n o f t o x ic e f f e c t s o f mammals e a t in g .f is h and Ignoring th e p o s s ib le argument th a t f is h per se must be p r o t e c t e d . Mr, W right (M onsanto) s a id th e proposed standard says both. In s a lt water, standards are proposed that would p r o t e c t th e s p e c ie s th a t e a t organism s c o n ta in in g PCB. In fr e s h w a te r . I f 0 .5 ppm In salm on eggs c o r r e la t e s w ith < 5 ppm In salmon th e n we are p r o te c tin g salm on. He a ls o s a id th a t th e ch r o n ic l i m i t s and b io m a g n lflc a tio n l i m i t s he was proposing would p r o te c t th e s p e c ie s th e m se lv e s. Ve sh o u ld , however, beware o f argu in g f o r h ig h e r l e v e l s in f i s h because we cou ld draw EFA and FDA In to c o n f l i c t * The FDA l e v e l s In fo o d , f i s h e t c . , are tem porary to le r a n c e s and any arguments a g a in st t h e ir v a lid it y could lead to a reduction in th ese toleran ces. Hr* Savage (M onsanto) q u er ied w hether r a is in g th e l e v e l in organisms could cause p o ssib le danger to predators. Dr* Simons (O .E .) quoted from page 39 o f th e B a sis & Purposes document which s t a t e s th a t th e body burdens o f b ir d s and mammals sh ou ld not in c r e a s e over p r e se n t l e v e l s . Page 51 o f th e same document c i t e s a N a t. Acad. S o l . r e p o r t which g iv e s 2*0 ppm PCB as to le r a b le le v e l In fle s h o f whole f i s h . 2 .0 s 0 .1 ppm PCB 20 0 ,60 6 Is given as to le r a b le le v e l In water divided by a sa fe ty fa cto r o f 5 t o g iv e a maximum PCB c o n c e n tr a tio n in w ater o f 0 .0 0 2 ppm. Thus EPA a c ce p ted 2 ppm PCB l e v e l in f i s h but g ot t o w ater c o n c e n tr a tio n o f 0 .0 0 2 ppm by u s in g a h igh l e v e l o f 2 0 0 ,0 0 0 fo r b io m a g n lflc a tio n and an a r b itr a r y fa c to r o f 5 * I f we were t o r e v is e th e proposed EPA standard by: (l) (ll) u s in g 2 . 0 ppm as ch ro n ic l i m i t in fr e s h w ater s p e c i e s in s te a d o f 0 . 5 ppm; su b stitu tin g 30 ,0 0 0 Instead o f 200 ,000 for blom agnlflcatlon factor; and ( 1 1 1 ) ignoring sa fety factor o f 0 .5 th en th e maximum p e r m is s ib le d isch a rg e in l b . PCB p er day would be: 2 .0 10 .0 0 0 T 5 A ~ 3.6 lb . y V O 'SO x x Foni ? i8 a &M 0 0 7 2 a 9 167 10- Por th e p la n t s it u a t io n on a r iv e r w ith a flo w o f only 100 c fs the d isch arge would be 0 .0 3 6 lb /d ay or 9 .0 lb . per 250 work-day year. These le v e ls are s t i l l fa r below^the 5 lb ./d a v T i v e n in ARsri"c - i o 7 . I t i s th e r e fo r e apparent th a t o th e r a s p e c ts o f PCBa must be h ig h lig h t e d In ord er to j e t away from PCB d isch a rg e l e v e ls as low as even our " r e v ise d 1 p ro p o sa ls. A spects to c o n c e n tr a te on are: ( l ) D e f in it io n o f PCBa th a t e x clu d es b io d eg ra d a b le hom ologs. T h is co u ld e x c lu d e 9<# or b e t t e r o f A ro clo r 1016 and 6 5 $ o r b e t t e r o f A ro clo r 1242. On th a t b a s i s , d isch arg e le v e ls would be as fo llo w s: PCB Type Stream Discharge (lb.PCB e q u lv a len t/d a y ) Plow ( c f s ) "TOC Wright Slmons/Wrlght Any PCB Any PCB A roclor lOlb A roclor 1016 A roclor 1242 A roclor 1242 10 ,0 0 0 10 0 10 0 10 ,0 0 0 10 0 0 8O 0.0648 0.000648 0.648 0.00648 '0'.'19'4 ' 0.0019 0 .9 18 0 .0 0 9 18 9.18 0 .0 9 18 "5775 0 .0 27 3 .6 0.0 36 "36 .0 ' 0 .36 10 .8 0 .10 (2 ) Try to change stream flow s from the p resen t value of the flow rate In cubic fe e t per second ( c f a ) expressed as the probable low rate occu rrin g during a 7 co n secu tiv e day period once In 10 years at the e fflu e n t p oln tT -------------- I f the average flow r a te over a p er io d o f tim e (to be agreed on) was u sed , the low est flow r a te In the eq u ation could con ceivab ly be r a ised by a fa c to r o f 10 from 100 to 1000. In the Slm ons/V rlght versio n for a standard th e A roclor 1016 d isch arge could be ra ised to 3 .6 l b . /day a t 1000 c f s flow and A ro clo r 1242 to 1 .0 l b . / day a t 1 0 0 0 c f s flo w . (3 ) Magnitude o f PCB P o in t-S o u rces I t Is p o s s ib le th a t EPA and e n v ir o n m e n ta lists are t o t a l l y m isinform ed on th e number o f p la n ts s t i l l u sin g PCBs. In the U .S. today there are: ADM 007290 10 0 1 9 1 9 168 -1 1 - 1 PCB m anufacturing p la n t "-1 8 c a p a c ito r p la n ts u s in g PCB *^27 tra n sfo rm er m anufacturing p la n ts u sin g PCB In the past th ere were probably 1500-2500* p lan ts using PCBs. Only 2 -3 # o f th e s e p la n ts co n tin u e t o u se PCB today. * (Subject to c lo se r checking I f necessary) In th e p a s t ~ 9 7 o f p la n ts u sin g PCBs p u r c h a se d ~ 4 0 m illio n pounds o f PCB per y e a r . M onsanto's PCB s a le s p olicy has therefore - reduced number o f u s in g p la n ts t o ~ 2 - 3 o f previous to ta l. - e lim in a te d ^*40R l b s . PCB s a l e s p er y e a r . The EPA .stan dard would lim it PCB d isch a rg e p er p la n t to 0.0648 lb ./d a y or ~ 3 .2 lb ./d a y across the U .S. (~-50 p la n t s ) . T his equates to * 8 0 0 pounds in a 250 work-day y ea r. Sin ce fis h have survived throughout the 40+ years t h a t PCBs have been produced and w id e ly u se d , th e stan d ard proposed by EPA seems fa r to o d r a s t i c . Turning a g a in to th e Slm ona/V right p rop osal we can e stim a te th e e f f e c t In term s o f annual PCB d isc h a r g e In to w ater a cro ss th e U .S. at 1000 c fs : D isch arge. As D isch a rg e (lb ./d ay) No. P la n ts US T o ta l per 250 days (pounds) As P e r s is te n t PCBs D ischarge No. US (lb ./d a y ) Plants Tota] Any PCB Aroclor 1016 Aroclor 1242 Aroclor 1254 3 .6 3 .6 1.0 8 0 .3 6 * 1 900 18 16200 4 1080 23 2 0 7 0 20 .25 0 1 .2 1 300 0 .3 6 18 16 20 0 .3 6 4 360 0 . 3 6 23 2 0 7 0 4310 * P lan t la on r iv e r In ex cess o f 10,000 c f s . U sin g t h i s te c h n iq u e ah argument can be made In fa v o r o f th e ANSI C-107 p r o p o sa l o f 5*0 l b ./ d a y . AM 00791 Foni 220 169 -12- Proposed Effluent^ Standards Dr. Simona (Q. E . V summarized the p o in ts he f e l t had to be d e a lt w ith in tryin g to change the proposed standard: 1 . H igher p e r s is t e n c e o f h ig h e r FCBs v e r su s a lleg ed lower acute to x icity . 2 . Background l e v e l s o f FCBs 3* W ritten t e s t lo o n y o f p a r t ic ip a n t s and c o r r e la tio n T oxicity SPA B a s is 4 Purpose document (page 30) s t a t e s th a t 96 hour LC-50 t o f i s h cannot a d eq u a tely measure t o x i c i t y o f PCB. Where I s tim e dem arcation between acute and c h r o n ic . Chronic e f f e c t s can be e ith e r le th a l or n o n -leth a l. Why are PCBs on th e l i s t on t o x ic grounds? LD-50 f o r PCB I s such th a t I t Is not c o n sid e r e d t o x ic to humans. For p r o t e c t io n o f a q u a tic l i f e the N at. A ca. S c i . s e t a 96 hour LC-50 o f 10 ppm o r l e s s . In p rop osin g a d e f i n i t i o n fo r PCBs, Dr. Simons (Q .E .) f e l t we should str e ss: (a ) lack o f p e r siste n c e o f homologs below te tr a c h lo r o b lp h e n y l (b) chronic t o x ic it y does not a r is e fo r the lower homologs because they are n o n -p e r siste n t. (c ) Ignore acu te t o x i c i t y - no r e a l d iffe r e n c e s between A roclor 1016, 1242 and 1254.-* P a r t ic ip a n t s need t o c o n sid e r : Do we have th e b eat d e f in it io n ? In th e t e n t a t i v e EPA a n a ly t ic a l method we sh ou ld tak e note th a t in th e t a b le on p .3 - 2 2 . the p ercen tage o f PCB was not c o n t r o lle d . M r/C a r lso n (E .U .C .) p oin ted out th a t in i t s p resen t form the stan d ard co u ld sa d d le p r e sen t PCB u se r s w ith a l l o th e r d i s c o n tin u ed u s e s . Dr. Richard (M onsanto) p o in te d out th a t PDA and Boxboard M anufacturer's A sso cia tio n had agreed on a p rotocol th a t p r o tec ted r e c y c le paper u sers from Just such a s itu a tio n . Mr. Bergen (M onsanto) asked th a t c o p ie s be c ir c u la t e d to p articip an ts. . AON, 007292 F,nni22i 170. o - 13- Ve need to word our d e f in it io n s to exclude r e s id u a ls . P a r tic ip a n ts should exchange proposed d r a fts on wording r e g a r d in g r e s id u a ls by March 7 . 0 . E . s t a t e d we sh o u ld n o t approach th e h e a r in g on th e b a s is th a t th in g s c a n 't be done. Rather take thc_propoaed standard and p o in t_ o u t what I t means in r e a l l i f e * In G .E .'s case they use X H lb ./y e a r and y e t c a n 't lo s t 0 .5 drops per day. Stream flo w r a t e s make th e m a tter w orse. T his I s a p o in t on which Dr. Thompson should be cross-exam in ed . Of th e p a r tic ip a n ts p r e sen t, 5 p lan ts d isch arge Into sewers with o u t le t s Into r iv e r s (very sm all except In 2 c a s e s ) . Three p lan ts discharge Into sm all r iv e rs. No one a t th e m eeting cou ld cope w ith th e EPA stan dard as I t I s proposed. Only Jard expressed an opinion on what le v e l they c o u ld l i v e w ith . (Jard s t a t e d 27 l b . Aroc l o r 1016 per day. T h is would be 2 .7 l b . PCB by our p rop osed d e f i n i t i o n . ) n AuM 0072 F001222 171 o -14- P a r t lc lp a t lo n t EPA H earing D e fin ita p a r t ic ip a t io n ; Monsanto G. E, W estinghouse U n d ecid ed : E lectrical U tilitie s Jard NEMA Mo p a r t i c i p a t i o n : E le c tr o n ic Components M allory O b je cto r s o f reco rd co u ld adopt non-responding company as w itness. G .E .'s testim ony w ill f a l l Into the follow in g areas: - E x p la n a tio n o f why PCBs are used - Consequences o f ban on customers - Inadequacy o f EPA/Nat. Acad. S c l. statem ents - How sta n d a rd s would ap p ly to G.E. - Inadequacies o f the Standard d efin ition m ethodology lo g ic behind the standard Other contrib utory a ctio n s: - Involve Pederal Energy O ffice ( e .g . Aerovox l e t t e r on motor-run cap acitor co n trib u tio n to ease energy c r is is .) - Involve F .E .O ./oth er agencies along lin e s o f p e tro c h e m ica l p rod u cers' PEG r e p o r t. * - Power System s Group o f IEEE w i l l c i r c u l a t e a p o s i t io n ' paper on PCBs (te c h n ic a l a s p e c t s ) In th e d i e l e c t r i c In d u stry to C ongress, EPA, FEO and D ep t, o f Commerce (ta r g e t d ate: A p r i l ) . AOH 00729* i n m 223 172 Action Plans 1. (V. B. Papageorge) Circulate to participants copies of FDA/Boxboard Manufacturers protocol on PCBs In recycle paper. 2. (Participants) Exchange drafts on testimony regarding PCB realduals/background levels with each other by March 7 (Monsanto contact should be V. B. Papageorge.) 3. (Participants) Submit to V. B. Papageorge their thoughts on proposed PCB definition (to exclude 1*4 chlorine homologs). 4. (Participants) Communicate with each other on how best to handle sedimentation phenomenon (as raised by Mr* Sheppard of Vestlnghouse) 5- ( S. Tucker) Send out name of ASTM contact for participation In round-robin on proposed EPA analytical method* 6. (Participants) Write to Dr. Oaller of Commerce Dept, opposing EPA standards* (See Oaller letter to Monsanto and Monsanto response.) 7. (Participants) Those who have not responded to EPA can still write Dr. Thompson by March 2 5 . 8. (A. Salazar, NEKA) (a) Get feedback from Sangamo/McOraw Edison on the proposed standards. (b) Determine role NEKA, will take on affldavlts/testlmony at EPA hearing. 9. (V. B. Papageorge) Obtain PEG report and send to Mr* Nelson (G.E.)* 10. (Participants) Involve P.E.O. in EPA Hearing along lines of Aerovox letter to Secretary Sinon* F0ft1W4 AOM 07295 173 Monsanto U oA stnto C o m ptitf 8 0 0 N. Lindbergh lo u le va rd St. lo gt. M issouri 63168 Phon; O U I 664-1000 March 12, 1974 \i Mrs. B etty J . B illin g s Hearing Clerk Environmental P rotection Room 1 0 1 9 - E a s t T o w er 4 0 1 "M" S t r e e t , S.W. W ash in g to n , D, C. 20460 Agency Re: Proposed Toxic P o llu ta n t E fflu e n t Standards f o r A l d r i n - D i e l d r i n , Et A1 FJPCA (307) - Docket No. 1 Dear Mrs. B illin g s : I n a c c o r d a n c e w i t h t h e ORDER AND NOTICE o f J u d g e W i l l i a m J . 3v:eeney d a te d F eb ru ary 8, 1974, en clo sed a re the o r ig in a l and th re e copies of the w r itte n testim ony w ith a t t a c h m e n t s s u b m i tt e d on b e h a l f o f M onsanto Company i n connection with the above described m atter. Yours very tru ly PSP/jmd Enc. Phocion S. Park Senior Attorney 174 FOOl 225 i 100-3 A i I Monsanto: M o n s a n t o i n d u s t r i a l c n i m i c a l i CP. too N. ualrfft lovUvtr Si. lami. Un s o wn 83106 Rftsft: 014) 184 *1000 )i i I n Re: PROPOSED TOXIC POLLUTANT EFFLUENT STANDARDS FOR LDRINDIELDRXN, ET AL - FVPCA (307) DOCKET NO. 1 < Sesee of M issouri ) County of Se. Louis ) , s : V. B. F ip a g e o rg e , being f i r s t duly sworn s s y s : My name i s W. B. P ap ag eo rg e and I a a M anager, P roduce A c c e p ta b ility fo r the F u n c tio n a l P roduct G roups, Monsanto I n d u s t r i a l Chem icals Company, an o p e ra tin g u n it o f Monsanto Company. I am a g ra d u a te o f U a sh in g to n U n iv e r s ity , S t. L o u is , M issouri w ith a B achelor of Science degree in Chemical E ngineering and have receiv ed a M aster of Science degree in Chem ical E ngineering-from th e seme i n s t i t u t e . I ea a R egistered P rofessional Engineer in the s ta te of M issouri. I have b e en employed by M onsanto Company f o r a p p ro x im a te ly 22 y e a r s , d u rin g which p e rio d I have serv ed es an e n g in e e r, m aintenance superintendent, d is trib u tio n superintendent, m anufacturing su p erin ten d e n t, p la n t manager end manager of e n v iro n m e n ta l p r o t e c t i o n . I n ay p r e s e n t p o s i t i o n I am re s p o n sib le fo r aeelng th a t th e q u a lity of products produced by two b u s in e s s groups in M onsanto Company i s p r o p e r ly m a in ta in e d . One o f th e b u s in e s s groups w ith in my a re a o f r e s p o n s i b i l i t y i s th e S p e c ia lty P roducts B usiness Group which m anufactures and m a rk e ts p o ly c h lo r in a te d b ip h e n y l (PCS) p ro d u c ts f o r use as d i e l e c t r i c f l u i d s in tra n s fo rm e rs end c a p a c i t o r s . I am a member, and have served as chairm an, o f a committee of the N atio n al E le c tric a l M anufacturers A sso ciatio n which has reviewed th e e n v iro n m e n ta l e f f e c t s o f PCBs and h as recommended p ro c e d u re s to u s e r s of PCBs which sh o u ld m inim ize th e p o s s i b i l i t y o f e n tr y o f PCBs in to th e en v iro n m en t. ult *1 U t n i m t i C a rn i* Ay 175 F 0 0 1 9 .9 S .1003 2- MONSANTO COMPANY'S POSITION AND recommendations > * A* a m a jo r p ro d u c e r and s u p p l i e r o f p o ly c h lo r in a te d b ip h e n y ls (PCBs) to th e .e le c tric a l industry for fir e re s ista n t d ie le c tric flu id a p p l i c a t i o n s , we have review ed and e v a lu a te d th e e f f lu e n t s ta n d a rd s fo r th ese m a te ria ls in proposed Parc 129, Subpart I , Chapter I of T i t l e 4 0 , Code o f F e d e ra l R e g u la tio n s . P u rs u a n t to t h i s re v ie w , we subm it th e follow ing consents and recom m endations: 1 . The p ro p o se d e f f l u e n t a ta n d a rd s f o r PCSs a r e u n w arran ted and p r a c tic a lly and econom ically u n a tta in a b le . 2 . A c tio n s by Monsanto and i t s c u sto m ers, which have r e s u lte d i n l i m i t i n g th e u se o f PCBa o n ly to e l e c t r i c a l a p p lic a tio n s in h erm etically sealed 'u n its, have d ram atically reduced th e q u a n t i t i e s o f th e more p e r s i s t e n t PCBc in tr o d u c e d d ire c tly in to the environm ent. 3 . The d e f i n i t i o n o f PCBs in S e c tio n 1 2 9 .0 9 a , S u b p a rt I sh o u ld be changed to read: " P o ly c h lo rin a te d b ip h e n y ls (PCBs) means m a te r ia ls co n tain in g the b ip henyl group which is c h lo rin a te d and which have been shown to p e r s i s t and r a p id ly bioaccum ulate in the aq u atic environm ent. These ch lo rin ated biphenyls are id e n tifie d as those components having gas chrom atographic re te n tio n tim e s g r e a t e r th a n 60, r e l a t i v e to o . p -DD1 0 0 .- u n d e r th e s ta n d a rd c o n d itio n s recommended in th e EFA PCS t e s t m ethod." e 4. The accuracy and re p ro d u c ib ility of r e s u lts a tta in a b le betw een la b o ra to rie s using c u rre n tly a v a ila b le sam pling and a n a ly tic a l tech n iq u es are q u e stio n ab le and fu r th e r stu d ie s a re recommended. 5* The proposed PCB e f f l u e n t s ta n d a rd i s b a se d on In a d e q u a te to x ic ity in fo rm a tio n , on n o n -ty p ic a l f is h sp e c ie s and on an u n u su ally high and a r t i f i c i a l bioaceum ulatlon fa c to r. Fundam ental s c i e n t i f i c a l l y - b a s e d d a ta i s la c k in g and no re s p o n s ib le s ta n d a rd s c a n be develo p ed a t t h i s tim e . Ue recommend t h a t s tu d ie s be conducted to o b ta in the re le v a n t .d ata and chat e fflu e n t sta n d a rd s be e s t a b l i s h e d w hich a re a p p r o p r ia te fo r th e u n iq u e c o n d itio n s e x istin g at each point source. 176 ... E0Q1227 100 6* Va o b je c t to a1 l i m i t i t Io n o f 10,000 cubie f e e t p e r second b e in g a r b i t r a r i l y a s s ig n e d a s a maximum scream f l o v , v ith o u c a sound ta c b n ic a l b a sis dem onstrating adverse a ffe c ts . 7 . The p re s e n c e o f background le v e l s of FCSs a t p o in t s o u rc e s sh o u ld be co n sid ered vhen determ ining e f f lu e n t le v e l s . The fo llo w in g d e f in itio n of "Background" should be added under S ection 129.01a: " 'B ackground' means amounts of to x ic p o llu ta n t (1) p re s e n tly found in the waterways of th e U nited S ta te s (in clu d in g the Intake w aters of a d is c h a rg e r), o r (2) a risin g out of operations su b ject to th is P art th a t occurred before the effectiv e date of th is F a rt, b u t were not d isch arg ed to the waterwaya of th e U nited S tates before the e ffe c tiv e date of th is F a rt." 8. T echnology f o r th e a tta in m e n t o f th e p ro p o sed FCB e f f l u e n t sta n d a rd has not been dem onstrated and Is n o t a v a ila b le to th e in d u s try . Unachlevement of th e s t r i c t stan d ard proposed would h a v e th e e f f e c t o f a ban on th e use o f PCBs w ith s e r io u s econom ic and s o c ia l consequences very thoroughly d escrib ed in an Impact h s ta te m e n t su b m itte d to th e Agency on Jan u a ry 15, 1974, by th e G en eral E l e c t r i c Company. The ch em ical s tr u c tu r e o f p o ly c h lo rin a te d b ip h e n y ls (FCBs) has been known f o r n e a r ly 100 y e a r s . I t was n o t u n t i l th e l a t e 1920a t h a t a u s e f o r FCBs was found -- a s a d i e l e c t r i c f l u i d in tr a n s f o r m e r s . The p r o p e r t i e s o f PCB -- i n e r t n e s s , f i r e r e s i s t a n c e and a n o n -c o n d u c to r of e le c tr i c ity -- are p e rfe c tly su ite d to chose e le c tr ic a l a p p lic a tio n s where h ig h -v o ltag e arcin g could occur; p o ssib ly re s u ltin g In se rio u s f i r e s o r damage to th e equipm ent. Commercial p ro d u c tio n o f FCBs began in 1929. As th e u n iq u e p r o p e r t i e s o f th e m a te r ia l became known, new u ses were fo u n d . For exam ple, t h e i r `f i r e - r e s i s t a n t n a tu r e made them e x c e lle n t c h o ic e s f o r u se in h e a t tra n s fe r flu id s . T heir In ertn ess gave lo n g -la stin g q u a litie s to lu b ric a n ts . T heir use in su rface co atin g s improved w aterp ro o fin g ch aracteristics. la n d lin g of the product a t the m anufacturing le v e l has not p resen ted problem s as long as th e normal in d u s tria l hygiene p ra c tic e s were fo llo w e d and FCBs have alw ays been c o n sid e re d l e s s h aza rd o u s th a n many oehsr chem icals in everyday use. _o Kftftl 'T' * " r r 177 100l .-I T h e r e f o r e , 1c ap p ea re d t h a t PCB v e re a u n iq u e p ro d u c t v h lc h mee Im portant needs of In d u stry . When q u e s tio n s ab o u t th e e f f e c t o f PCBs on th e en v iro n m en t f i r s t s u r f a c e d , M onsanto Company rev iew ed I t s p ro d u ct l i n e a n d 'th e a p p lic a tio n s f o r th e s e p ro d u c e s . As more d a ta v e re dev elo p ed c o n c e rn in g th e e f f e c t o f PCSa, M onsanto topic s te p s to re d u c e th e e n try o f PC3 in to th e ` e n v iro n m e n t. The Company s to p p e d th e s a l e o f PCBs f o r u se i n v a r io u s a p p lic a tio n s , except where no acc e p tab le a lte rn a tiv e s were a v a ila b le . T oday, PCBs m a n u factu red by M onsanto Company a r e s o ld o n ly to th e e l e c t r i c a l In d u stry fo r use in closed systems as a d ie le c tr ic flu id la tra n sfo rm e rs and c a p a c ito rs -- a p p lic a tio n s fo r which th e re e x is t no acceptable s u b s titu te s . Thus th e s itu a tio n today i s d r a s t i c a l l y d if f e r e n t from c o n d itio n s which e x iste d only th re e y e srs ago. Today about 40 m illio n pounds p e r year a re being e a re fu lly used in the U nited S ta te s by le s s than 50 Monsanto custom ers In th e m anufacture of se a le d e le c tr i c a l equipm ent. P r io r to 1971, c lo s e to 80 m illio n pounds p er y e a r v e re used by thousands of custom ers. This lends perspective to the cu rren t debate o v e r m odest lo s s e s o f PCBs to w aterw ay s. Our m a n u fa c tu rin g and s a l e s r e d u c tio n program v a s .a u n i l a t e r a l a c t i o n tak en by Monsanto and vas baaed on our e v a lu a tio n o f developing environm ental data. The I n te r d e p a r tm e n ta l T ask F o rc e on PCBs In I t s r e p o r t ( l) q c o n c u rs th a t th e safety b e n e fits derived ju s tify the continued use In d i e l e c t r i c a p p lic a tio n s . Recommendation 6 under F in d in g s, C onclusions and Recommendations read s as fo llo w s: " 6 . The u se o f PCBs sh o u ld n o t be banned e n t i r e l y . T h e ir continued use fo r tran sfo rm e rs and c a p a c ito rs in the near fu tu re la conaldered necessary because of the s ig n ific a n tly increased r is k of f ir e and explosion and th e d isru p tio n of l e e t r l e a l s e r v i c e v h lc h would r e s u l t from a ban on PCB u a e . A lso , c o n tin u e d u se o f FCBs in tra n s fo rm e rs and c a p a c ito rs p re se n ts a minimal r is k of environm ental c o n ta m in a tio n . The Monsanto Company, th e s o le dom estic producer, has reported v o lu n tarily elim inating Its d i s t r i b u t i o n o f FCBs to a l l e x c e p t m a n u fa c tu re rs of e le c tr ic a l tran sfo rm ers and c a p a c ito rs .'1 Numbers.in parentheses r e f e r to referen ce l i s t attach ed . 001229 178 100G Recognizing ch need for proper control la the handling end use o f PCBs, representative of the transfon&er and capacitor In d u str ie s, u t i l i t i e s and governmental agencies under the i n i t i a l auspices of the H ational E le c tr ic a l Manufacturers A ssociation formed American N ational Standards In stitu te Comic tee C-107. Proposed gu id elin es (30) for the handling and disposal of d ie le c tr ic flu id s have been published. These guidelines r e fle c t the industry's understanding of the need for proper control and have contributed s ig n ific a n tly tovard achieving this objective. Propoaals for the control of PCBs in tern ation ally were considered by the member countries of the Organization for Economic Co-operation and Development (OECD) and in February, 1973, they adopted an agreement (31 which r e s t r ic t s the use of PCBs to d ie le c tr ic a p p lica tio n s, non-food related heat transfer flu id app lication s and hydraulic flu id a p p lica tio n s In mining equipment. This agreement i s le s s r e s tr ic tiv e than Monsanto's a le s p o lley since i t supports the continued use of PCBs in heat tran sfer and hydraulic flu id s . Ve have reviewed with considerable in te r e st the e fflu e n t standards proposed for polychlorinated biphenyls in new Part 129, Subpart I , Chapter I of T itle 40, Code of Federal Regulations and have o b jectio n s relatin g to the following: 1. D efinition of polychlorinated biphenyls. 2. Sampling and an a ly tica l methods. 3. Toxicity data. 4. Bioaccumulation factors. 5. Safety factors. * 6. Stream flow r a te s. 7. Background le v e ls of polychlorinated biphenyls. Economic considerations. DEFINITION OF POLTCSLORINATED BIPHENYLS Commercial p o ly c h lo rin a te d b ip h e n y l p ro d u e ts , o f which Aroclor* p ro d u c ts are exam ples, are produced by d ir e c t c h lo rin a tio n of b ip h en y l; th e degree of ch lo rin a tio n being chosen to provide desired p ro p e rtie s. These p roducts a re in a l l cases m ulti-com ponent m ixtures and not ^single e n t i t i e s a s im p lie d by th e commonly employed acronym "PCBs". :F O fi1 % * 0 179 1 0 0 0 -6-- V h lla 1C l a w a ll u n d e rs to o d and a c c e p te d t h a t p o ly c h lo r in a te d b ip h e n y l lao aara have a unique sec of p h y sical and chem ical p ro p e rtie s , I t la a p p a re n tly not understood th a t they bioaccum ulate, d is s ip a te and biodegrade a t d iffe re n t ra te s . T hlf lack o f understanding is re fle c te d in the d e fin itio n proposed I n th e EPA T oxic P o l l u t a n t E f f lu e n t S ta n d a rd s ( F e d e r a l R e g i s te r , V o l. 38 Ho. 247 p ag e 35393 S e c tio n 1 2 9 .0 9 a) and ve q u o te : ' "Aa used in t h i s S u b p art Che te rm : P o ly c h lo r in a te d b ip h en y ls (FCB's) means m a te ria ls c o n tain in g the biphenyl group which have been c h lo rin a te d to varying d a g re e a . T h e re a r e 210 p o s s ib le d i f f e r e n t PCS com pounds." Ve o b je c t to th is d e f in itio n because i t Im plies th a t a l l p o ly c h lo rin a te d biphenyl Isomers are of equal environm ental concern, l . e . , th a t they a l l p e r s i s t and b io aecu m u late in th e same manner In our environm ent. I t has been v e il e s ta b lis h e d by academ ic, governm ent, end I n d u s tr ia l re se a rc h e rs th a t th is Is sim ply not tru e . Environm ental m onitoring programs have c le a rly dem onstrated th a t, w ith th e exception of d ire c t h ig h -lev e l c o n tro lla b le re le a se near p o in ts of m anufacture or u s e , th e PCBs found i n o u r en v iro n m en t a r e th e more h ig h ly c h l o r i n a t e d o n e s, l . e . , th o se c o n ta in in g predom inantly fiv e or more c h lo rin e atoms p e r b ip h en y l m olecule (2 th ru 1 3 ). This la tru e even though th e lo v er p o ly ch lo rin ated biphenyls have c o n s t i t u t e d more th a n 651 o f a l l th e PCBs m a n u fa ctu red o v er th e y e a r s . T his la stro n g evidence th a t th e lower p o ly ch lo rin ated biphenyls degrade ra p id ly . I t fu r th e r dem onstrates Chat even under c o n d itio n s o f u n lim ited u se, and w ithout s p e c ia l p recau tio n s to avoid re le a s e In to our environm ent (which i s not the case now), th a t th e lower p o ly c h lo rln a ti biphenyls degrade rap id ly enough to prevent bioaccum ulation (4, 5, 6, 27, More r e c e n t l y , i t h a s a ls o been d e m o n stra te d i n la b o r a to r y e x p e rim e n ts th a t ch lo rin ated biphenyl isom ers, re a d ily undergo b a c te ria l d eg rad atio n a t ra te s dependent upon th e number o f c h lo rin e s per biphenyl m olecule* (17, 1 8 , 19, 20, 21 and 3 7 ). There a re a lso good in d ic a tio n s th a t amblen e n v iro n m e n ta l PCB l a v e l s a r e d e c r e a s in g a t r a c e s more r a p id ly th a n pred icted (14, 15. 16). T ht ra p id m etabolism of th ese c h lo rin a te d learners end th e ir la ck of Im portance as c o n trib u to rs to the ch lo rin ated biphenyl tis su e burdens la evidenced In th e r e s u lts o f numerous s tu d ie s . Rlsebrough (2) r e p o r te d c h a t th e c h lo r in e c o m p o sitio n o f th e PCBs d e te c te d i n A t l a n t i c Ocean a o o p len k to n was a p p ro x im a te ly 541. He c o n clu d e d "U .S. p r o d u c tio n o f A ro c lo r 1254 in 1970 amounted to 12 m illi o n pounds -- o n ly one q u a r te : Moral 180 100C o f th e p ro d u c tio n o f 49 B i l l i o n pounds o f A ro c lo r 1242. I t m ig h t be e x p ected th e re fo re ch at b ip h en y ls w ith fe v e r c h lo rin e atoms would predom inate in p la n k to n ic samples u n le ss th e se compounds were s e le c tiv e ly degraded." S im ilar fin d in g s in fre sh w ater and m arine fish e s v e re re p o rte d by Zltlco (3) and Jen se n , e t e l . , (4 ). The d isap p earan ce of th e lo v e r c h lo rin a te d homologs in e x tr a c ts of tis s u e s from b ird s (3 , 34) and mammals (6 , 33) i n d i c a t e r a p id m e tab o lism o r e x c r e tio n o f th e lo v e r c h l o r i n a t e d hom ologs. As a r e s u l t o f th e m e ta b o lism a n d /o r e x c r e t i o n o f Che c h lo r in a te d b ip h e n y ls c o n ta in in g l e s s th a n f i v e c h lo r in e atom s per m olecule, th e ir co n trib u tio n to the e fflu e n t should not be used la m easuring p o ly c h lo rin a te d biphenyl e fflu e n t from a f a c i l i t y . On th e b a s i s o f th e s e d a ta i t i s u n r e a l i s t i c to c o n s id e r a l l p o ly c h lo rin a te d b iphenyls eq u iv alen t in term s of p e rs is te n c e and bioaccum ulatlo n as does the proposed reg u la tio n . T herefore, fo r environm ental p u r p o s e s , th e d e f i n i t i o n o f PCBs sh o u ld fo c u s upon th o s e v h lc h a r e o f co n cern and ve recommend th a t th e fo llo w in g d e f i n i t i o n be s u b s t i t u t e d fo r th a t proposed in S e c tio n 1 2 9 .09a, S u b p a rt.1 , T i t l e 40, Code o f Federal R egulations: " P o ly c h lo r in a te d b ip h e n y ls (PCBa) means m a t e r i a l s co n tain in g the biphenyl group vhlch is c h lo rin a te d and v h lch have been shown to p e r s i s t and r a p id ly bioaccum ulate in the aq uatic environm ent. These ch lo rin ated biphenyls are id e n tifie d as those components having gas chrom atographic re te n tio n tim es g r e a te r th an 60, r e l a t i v e to p,p-DDE * 100, under the stan d a rd c o n d itio n s recommended in th e EPA PCB t e s t m eth o d ." ANALYTICAL METHODOLOGY m Ve have no re a s o n to d o u b t t h a t th e recommended EPA PCB t e s t m ethod i s c a p a b le o f d e te c tin g p a r t s p e r t r i l l i o n (p p t) l e v e l s o f PCBs i n v a s t e w a te rs. However, our experience w ith an aly zin g in d u s tr ia l v a s te v a te r s f o r PCBs a t th e p a r t s p e r b i l l i o n (ppb) l e v e l prom pts us to be co n ce rn e d -a b o u t, th e fo llo w in g a r e a s , some of v h lc h a r e not co v ered edequately in the te s t procedure. X. Sam pling P ro c e d u re s 2. C o rrectio n fo r L aboratory and Reagent Background 3- C o r r e c tio n f o r Hon-PCB Sample I n t e r f e r e n c e s 4. A bsolute V e rific a tio n 1*001232 181 1 0 0 : 3 / \ -a- 5 P h y s i c a l S t a t e o f PCSa (A d a o rb e d /D isso lv e d ) 6 Q u a n t i t a t i o n 7* P r e c i s i o n an~ A ccuracy Our concern l i e s in the fa c t th a t any method, e s p e c ia lly one as complex a s a PCB a n a l y t i c a l m ethod, which i s to be used f o r e f f l u e n t c o n tro l purposes o u s t be thoroughly evaluated and i t s accuracy and r e p r o d u c i b i l i t y p ro v en . Zf t h i s la not done, th e e f f e c t iv e n e s s o f any e f f lu e n t l i m i t , no m a tte r what the le v e l, w i l l prove to be .d if f ic u l t, i f not im possible to determine* Tor example, ve have found th a t i f waste w ater stream s are not sampled p r o p e r l y , th e PCB l e v e l s found depend on t h e s a m p lin g p ro c e d u re employed and b e a r no r e l a t i o n s h i p to th e amount o f PCSs d is c h a r g e d . F or t h i s reason, sampling procedures used must be designed fo r the d isch arg e in q u e s t i o n and c l e a r l y s t a t e d . To o u r know ledge, t h i s has n o t b e e n d o n e . Ve a l s o n o t e t h a t no p r o v i s i o n s a r e recommended f o r c o r r e c t i n g t h e a p p a r e n t PCS l e v e l found i n a sample f o r l a b o r a t o r y and r e a g e n t background. I t Is our experience th at as one approaches the ppt le v e l, `t h i s background can s i g n i f i c a n t l y a f f e c t th e o b s e rv e d PCS l e v e l . With re g a rd to c o r r e c t i o n fo r .non-PCB sample i n t e r f e r e n c e s , v e f e e l C hat, w h ile th e p ro c e d u re n o te s many o f th e p o s s i b l e i n t e r f e r e n c e s , i t does not r e a lly address I t s e l f to those which a re more lik e ly to be in In d u s tria l waste w ater stream s. For th is reason, I f the e lectro n c a p t u r e chromatogram does n o t match th e PCB b e in g m an u fa ctu red o r u s e d , co m p lete a b s o l u t e v e r i f i c a t i o n of a l l components co unted as PCB m ust be v alid ated v ia an a lte rn a te technique such as gas chromatography/mass spectrom etry. Ve a l s o n o t e t h a t t h e recoemiended EPA PCB t e s t method does n o t s p e c i f y a aasQa o f d i f f e r e n t i a t i n g betw een d i s s o l v e d and ad so rb ed PCBs. Ve b e lie v e th is should be done since th ere is a d e f in ite d iffe re n c e in the to x ic ity and a v a il a b ili ty fo r bioaccum ulation of dissolved and adsorbed chlorinated hydrocarbons ( 2 4 , * V h l l t t h e scheme p ro p o s e d f o r e s t i m a t i o n ( q u a n t i t a t i o n ) o f PCBs i s l o g i c a l , I t s u f f e r s from th e same sh o rtco m in g as do th e m u l t i t u d e o f o t procedures which have been proposed. I t is an em pirical estim are and only a r e f l e c t i o n o f t h e r e a l PCB l e v e l . T h e r e f o r e , i t sh o u ld be d e te rm in e d v i a an a l t e r n a t e , m o r e - e la b o r a te p ro c e d u re how c l o s e l y th e c a l c u l a t e d PCB l e v e l s ( f o r each of th e c a s e s ) a r e to th e r e a l PCB l e v e l so t h a t th e y may be c o r r e c t e d . Fftfl 233 182 i o n : c -, I ^ l i i j j 1 i L i s t b u t s e c l e a s t , Che p r e c is io n end a c c u ra c y o f any p ro c e d u re p ro p o s as a sta n d a rd method should undergo a chore ugh in te r-la b o ra to ry e v a lu it I f t h i s h as noc a lre a d y been done, I t au se be c a rrie d ouc p r io r to th e use of th e procedure fo r enforcem ent purposes. The accuracy and p r e c i s i o n o f th e M onsanto PCB p ro c e d u re h a s been s u b je c te d to a p r e lim in a ry e v a lu a tio n . P rio r to th is e v a lu a tio n , ve probably would have o v e re stim a te d th e p re c isio n and accuracy o f our procedure. The ex act d e ta ils of the evaluation are av ailab le. ii B r ie f ly , sam ples v e re p rep ared by s p ik in g d i s t i l l e d w ater w ith 500 pob PCBs. In d iv id u a l p re p a ra tio n s In c lu d e b la n k s (no PCS), A rocloi ^1242 A roclor 1254 o n ly , A ro d o r 1260 o n ly , a l l 50-50 two-component m ixture and a 1 /3 , 1 /3 , 1 /3 .p rep aratio n containing a l l th ree components. Six sam ples o f e ac h m ix tu re v e re p re p a re d and a n a ly z e d by two e x p e r ie n c e d an aly tical lab o rato ries. Each r e s u l t , e x p re ssed in ppb o f th e In d iv id u a l A rocloi , v a s co n v erted to percen t of the to ta l added. A nalysis of v ariance vas run on a l l d a ta ta k e n to g e th e r and on each la b o ra to ry in d e p en d e n tly . . The 95Z c o n fid e n c e l i m i t s o b se rv e d f o r in d iv id u a l r e s u l t s w ere: E ith e r Lab 8 7 .5 + 5 5 .2 2 Lab A 81.3 + 46.4Z Lab B 9 3 .7 + 1 9 .2X . The r e p e a ta b ility fo r the in d iv id u a l la b s , based on re p e a t te a ta of sam ples having id e n tic a l prepared com positions v a s: Lab A + 42.02 Lab B 11.62 . Va f e e l t h a t th e s e r e s u l t s d e m o n stra te th e Im p o rtan ce o f e v a l u a t i n g the p r e c i s i o n o f any PCB p ro c e d u re . N ote t h a t th e t e s t d id n o t I n c lu d e sam pling problem s, used d is tille d v s te r fre e of In te rfe re n c e s, and vas c a r r i e d o u t a t a r e l a t i v e l y h ig h PCB l e v e l (500 ppb; 5 0 0,000 p p t) by tvo ex p erien ced la b o ra to rie s . I t Is expected th a t, i f sam pling probles v e r e In v o lv e d , end th e le v e l o f PCB p r e s e n t v a s ex tre m ely lo w , th e a c c u ra c y and p r e c i s i o n o f any PCB method v o u ld d e c re a s e c o n s id e r a b ly . Enfl1234 183 10070' 10- V -1 BACKGROUND FOR PROPOSED EPA EFFLUENT STANDARD, ^ la th e stab lish m erc of the proposed e fflu e n t stan d ard the p rin a ry b a sis f o r to x ic o lo g ic a l c o n s id e ra tio n cane from th e W ater Q u a lity C r i t e r i a . O cto b er, 1973. (F ed e ra l R e g iste r, Vol. 38, pages 29646 e t s a q ., F rid a y , O c to b er 26, 1 9 7 3 ). T hese c r i t e r i a w ere, in tu r n , b ased on W ater Q u a lity C r i t e r i a , 1 9 7 2 . by th e N a tio n a l Academy o f S c ie n c e s and th e N a tio n a l Academy o f E n g in e e rin g . The W ater Q u a lity C r ite r ia , O ctober, 1973. have n o t undergone th e norm al re v ie w , c r i t i c i s m , comment and r e v is io n b e fo re f i n a l a d o p tio n . We o b j e c t to th e u se o f c h a lle n g e a b le p o r tio n s of., a p ro p o se d p u b l i c a t i o n In the developm ent o f c r i t i c a l e fflu e n t stan d a rd s. We n o te i n W ater Q u a lity C r i t e r i a . 1972. in th o s e s e c tio n s p e r t a i n i n g to p o ly c h lo rin a te d b ip h en y ls, the frequent use of unpublished data and th e d istu rb in g use of q u alify in g phrases such as "...m ay adversely a f f e c t ..." , " ...a p p a re n tly re la te d ..." , or " ...th e w ork.. .su g g e st.. In our opinion, none of the discussions present adequate data to support e s ta b lis h m e n t of re s p o n s ib le e f f lu e n t s ta n d a rd s f o r FCBs. On page 5 o f W ater Q u a lity C r i t e r i a , 1972, th e Com m ittee em phasized th e Im portance in u n d e rsta n d in g th a t th e re i s a d i s t i n c t i o n .between c r i t e r i a and stan d a rd s and th a t th e words ware not in te rc h a n g e a b le nor o r they synonyms fo r words such as o b jectiv es or g o a ls . The re p o rt fu r th e r s ta te s th a t i t is necessary to e sta b lish s c ie n tific a lly -b a s e d recoomendacl fo r each a ssig n a b le w ater uae, implying a v a il a b ili ty of p r a c tic a l methods o f d e te c tin g and m easuring which can be a p p lie d to m o n ito rin g . Once th ese fundam entals are a v a ila b le , p o litic a l, s o c ia l and economical fa c to rs en ter in to the decision-m aking process to e sta b lis h stan d a rd s. In our o p in io n , th e se p ro ced u ral step s were n ot follow ed in a rriv in g a t th e propoaed e f f l u e n t s ta n d a rd s fo r PCBs. The maximum a c c e p ta b le c o n c e n tr a tio n in f r e s h w a te r t h a t would be p e rm itte d by th e proposed stan d ard la 0.002 m g/1. The ra tio n a le d e sc rib e e in th e S ta te m e n t o f B a s is and P u rp o se, T oxic P o l l u t a n t E f f lu e n t S ta n d a rd s la based on r e s u lts of a prelim in ary study which have suggested (n o t y e t p ro v e n ) a t h r e s h o ld PCB l e v e l fo r salmon egg m o r t a l i t y . We c an n o t a c c e p t th e s e le c tio n o f salmon as re p re se n tin g organism s which a re u s u a l o r may p o t e n t i a l l y be p r e s e n t in w a ter sy stem s n e a r f a c i l i t i e s d e s c r ib e d l a S e c tio n 1 2 9 .0 9 , Code o f F ed eral R e g u la tio n s. The c u m u la tiv e t e l e s o f PCBs In th e U n ited S t a t e s s in c e 1930 h as been e stim a te d to be ab o u t 500,000 cons and Chat t o t a l w orld p ro d u ctio n was p ro b a b ly 1 ,0 0 0 ,0 0 0 to n s ( 1 ) . About o n e - h a lf o f th e PCBs were used in a p p lic a tio n s w here containm ent was d i f f i c u l t and lo s s e s in to th e e n v iro n m e n t w ere common. W ith t h i s amount o f m a t e r i a l d is c h a rg e d i n t o the environm ent, i t is of considerable im portance to note chat ex ten siv e lo rn ?.r<5harm p re d ic te d by some th e o rie s has n o t been found and documented. 184 10070 r:r T h is le e k o f e v id e n c e l a d l e * t e s t h a t a l l o f Che PCBs do a o t p e r s i s t in th e environm ent s* * r e s u lt of fs e to rs such ss che b lo d eg ratlo n ve have d is c u s s e d p r e v i o u s l y . A ls o , th e PCBs thaL do p e r s i s t may n o t be a v a il a b le b e c a u se o f some f a c to r s n o t c le a r ly u n d e rsto o d a t p r e s e n t . One c h a r a c t e r i s t i c w h ich u n d o u b te d ly i s o f s i g n i f i c a n t im p o rta n c e i s th e a b i l i t y o f PCBs to a d so rb c o n s c io u s ly to p a r t i c u l a t e m a t t e r . U nder th e s e c o n d i t i o n s i can PCBs be r i g h t f u l l y c o n s id e re d to be e n v iro n m e n ta l, a c tiv e and, If so , to what degree? There e x ists s t present a c r i t i c a l need fo r d a ta r e la tin g to p a r titio n c o e ffic ie n ts between w ater and sedim ents and d iffu s io n c o e ffic ie n ts .in sedim ent (1 , 22, 39, 4 0 ). A lthough many r e p o r ts have been p u b lish e d on th e s u b je c t o f p o ly c h lo rin a te d biphenyls and liv in g organism s, the m ajority of th ese d e s c r ib e th e p re s e n c e o f PCBs in th e en v iro n m e n t. P re se n c e s h o u ld n o t be assum ed to im ply a d v e rs e e f f e c t . To o u r know ledge, no p u b lis h e d re p o rt e x is ts which c o n clu siv ely r e la te s the m o rta lity of any w ild lif e s p e c ie s to th e p re s e n c e o f PCBs. The only re p o rte d m o r t a l i t i e s a r e th o s e a c h ie v e d I n l a b o r a t o r y s t u d i e s . Not enough i s known a b o u t th e f a t e and e f f e c t o f PCBs i n th e n a t u r a l and d iv e r s e a q u a tic and m a rin e environm ents to p ro p e rly design lab o rato ry s tu d ie s . R esu lts from such stu d ie s are not e x tra p o la ta b le to the n a tu ra l s itu a tio n s and any co n clu sio n s d eriv ed from such stu d ie s must s t i l l be considered sp e c u la tiv e . Fundamental s c ie n tific a lly -b a s e d d ata is lack in g and, ini t s absence, the establishm ent of efflu en t standards for polychlorlnatec b ip h e n y ls cannot be made i n t e l l i g e n t l y and re s p o n s ib ly . In th e e s ta b lis h m e n t o f th e PCB e f f l u e n t s ta n d a rd f o r f r e s h w a te r system s a b io accu m u latio n f a c to r of 200,000 was s e le c te d . T h is f a c t o r h as no e x t r a p o l a t a b l e r e l a t i o n s h i p to e i t h e r th e r e s id u e s o f PCB i n salm on eggs o r to PCB r e s id u e s o f f r e s h w a te r fo ra g e f i s h . The o n ly published r e p o r t.(27) of an accum ulation fa c to r of the magnitude select was th a t f o r th e h ep ato p an creas of th e pink shrim p, Penaeus durarum . Even though an accum ulation of 204,000. in the hepatopancreas has o ccu rri a n e a r ly com placa e lim in a tio n o f PCB from t h a t t i s s u e was a c h ie v e d when th e shrim p v e r s p la c e d in w a te r f r e e o f added PCB. The e q u ilib r iu m whole body accum ulation p la te a u in d ic a te d an approxim ate accum ulation f a c t o r o f 2 2 ,0 0 0 . T h ese r e s u l t s a r e in agreem ent w ith chose r e p o r t e d b; S ta llin g s and Mayer (2 9 ), and w ith th e s tu d ie s of R yther (2 8 ), G relchus e t e l (24) end C rum p-W eisner, C a l (22) showing e q u ilib r iu m b lo m ag n lfl< tlo n fa c to rs between w ater and fis h ranging between 1,000 and 75,000 d ep en d in g on th e p re s e n c e and ab sen ce of sed im en t and th e s p e c i f i c PCB m ix tu re p r e s e n t. These d a ta would support th e s e le c tio n of a f a c t o r c o n sid e ra b ly lo v e r th an th e fa c to rs which were a p p lie d . F/HVI9.36 185 10070: % A rb itra ry s a fe ty f a c to r s were applied to the to le ra b le chronic l i c i t to e s t a b l i s h th e s o - c a l l e d " c r i t i c a l c h ro n ic l i m i t '' w hich was th e n used to com pute th e maximum a llo w a b le e f f l u e n t . These s a f e t y f a c t o r s w ere proposed to account fo r a m ultitude of v a ria b le s , including non-point so u rc e s, m u ltip le d isc h a rg e s and in d u s tr ia l grow th. The s a fe ty f a c to rs proposed w ere id e n t i c a l fo r 7 o f th e 9 m a te ria ls fo r which e f f lu e n t standards were p rep ared . These safety fa c to rs , re su ltin g in approxim ate tw o -fo ld r e d u c tio n s , a re so sm all a s to be o f no b e n e f ic ia l to x ic o lo g ic * c o n se q u e n c e . Ve recommend t h a t no s a f e ty f a c t o r be a p p lie d . I n e s t a b l i s h i n g th e e f f l u e n t s ta n d a r d s , an a tte m p t was made to d is tin g u is h betw een ty p e s o f re c e iv in g w aters by c la s s if y in g them as s tr e a m s , la k e s end im poundm ents, e s t u a r i e s and c o a s t a l w a te r s . Ve do n o t b e lie v e t h is a tte m p t to d is tin g u is h w ater b o d ie s i s by any m easure a d e q u a te . V e te r b o d ie s a r e u n iv e r s a ll y known to be complex sy ste m s w ith no two sy ste m s a l i k e . U lth a complex m a t e r i a l such a s p o ly ch lo rin ated bip h en y ls, the determ ination of p o ssib le adverse e ffe c ts in each w ater body becomes exceedingly d i f f i c u l t . The uniqueness of each w ater system a t each p o in t source must be co n sid ered . A key param eter used to fu rth e r d escrib e the w ater body is th e flow r a t e w hich wee l i m i t e d to th e p ro b a b le low r i t e o f stream flo w o c c u r r in g d u rin g s s e v e n -c o n s ecu tiv e - d * y p e rio d once In te n y e a r s . Ve do n o t agree th a t th is la r e a lis tic or appropriated In our opinion, ap p ro p rlat c o n tr o l 1 a ch ie v e d u s in g av erag e stream flow r a t e s . F u r th e r , th e maximum flo w r a t e t h a t can be u sed in .c a l c u l a t i n g th e d a l l y d ischarge p erm itted hi* been a r b itr a r ily se t a t 10,000 cubic fe e t p er second. T his lim it i s based on a nondegradation philosophy which to le r a te s lim ite d d iff u s io n and on e d e s ire to d isco u rag e in d u s try from lo c a tin g f a c i l i t i e s on la rg e main in la n d w aters and c o a s tlin e s . T his lim ita tio n d e p riv e s our s o c ie ty of th eaJu d ic io u s use of an im p o rta n t gre n a tu r a l re s o u rc e . D ischarge lim ita tio n s should be based on th e e f f e c t s a m a te ria l w i l l have on a w ater system , g iv in g c o n sid e ra tio n to i t s s iz t and flow r a t e . For FCBs, p roper c o n tro l w ill n o t occur by im posing maxlmimi flo w r a t e c o n d itio n s , b u t by a p p ly in g r e s u l t s from s c i e n t i f i c s t u d i e s w hich p r o p e r ly d e f in e how each w a te r sy stem resp o n d s to th e p re se n c e o f FCBs. KBS1DUAL POLYCHLORINATED BIPHENYLS B ecause o f t h e i r c h e m ic a l and p h y s ic a l p r o p e r t i e s , PCBs can be found in s o i l l and w aters a t p o in t sources long i f t e r e d isch arg e has o c cu rred . T h is s o u rc e o f PCBs to th e environm ent w i l l d im in is h w ith t i n e b u t i t s p re sen c e w i l l d i s t o r t and mask r e s u lts from c u rre n t c o n tro l a c t i v i t i e s . To m a in ta in c o n t r o l o f l o s s e s , em phasis sh o u ld be d ir e c te d tow ard d is c h a r g e s r e s u l t i n g from c u r r e n t and f u tu r e u s e s o f PCBs. Enm ?.37 186 ID 07 0 1 13 l l a e t th is problem of background le v e ls occurs w ith a l l m a te ria ls in trying d eg rees, ve propose th e follow ing re v is io n s : fro S ectio n 1 2 9 .0 1 c (b ), d e le te th e words " in In tak e w aters fo r a discharger". Add an a d d i t i o n a l d e f i n i t i o n in S e c tio n 1 2 9 .0 1 a : " 'B ackground1 means amounts of to x ic p o llu ta n t (1) p re s e n tly found in th e waterways of the United : .S tates (including the intake w aters of a d isc h a rg e r), o r (2) a ris in g out of operations su b ject to th is P art th a t occurred before the effe ctiv e date of th is P a rt, b u t were n o t discharged to the waterways of the U nited S ta te s before the e ffe c tiv e d ate of th is P a rt." ECONOMIC CONSIDERATIONS At o u r PCB m a n u fa c tu rin g f a c i l i t y , we d ev elo p ed and i n s t i t u t e d an a g g r e s s iv e c o n t r o l program w hich we d e s c rib e d b e f o r e th e E f f lu e n t S ta n d a rd s and W ater Q u a lity In fo rm a tio n A d v iso ry C o ra n itte e, EPA ( 4 1 ) . Y et, in s p ite of a l l our e f f o r ts , ve cannot today meet the proposed afflu en t standard. In response (42) to an in q u iry from th e U.5. D epartm ent of C o = e rc e , ve emphasized chat technology has not been developed to the p o in t th a t f a c i l i t i e s could be designed to meet a reaso n ab le stan d ard . However, a n a ly tic a l techniques suggest a conceptual design using adsorption, s e tt lin g and f i l t r a t i o n of aqueous w aste, follow ed by in c in e ra tio n o f th e a d s o r b e n t, p ro b a b ly c a rb o n . Ve e s tim a te th e c a p i t a l c o s t o f su ch a f a c i l i t y , sized to handle our p la n t waste, a t $600,000, not in c lu d in g a dedicated in c in e rato r for the disposal of the adsorbent m a te ria l. Annual o p e ra tin g c o a t would approxim ate $150,000. 'T h e v a lu e o f M o n sa n to 's a n n u a l PCB p ro d u c tio n i s a b o u t $8 m i l l i o n , w h ile th e v a lu e o f th e e l e c t r i c a l d e v ic e s made th e re fro m i s an o rd e r o f m agnitude l a r g e r . I f Monsanto were to cease p ro d u c tio n of PCBs, th e Jobe o f 55 em ployees would be e lim in a te d d i r e c t l y , w h ile th o se o f an A d d itio n a l 47 em ployees in a su p p o rtin g f a c i l i t y would be In je o p a rd y . `^Yho t o t a l p a y r o l l in v o lv e d i s on th e o rd e r o f $ 1 .5 m illi o n . The Im pact o f a PCB ban on o u r cu sto m ers can b e s t be d e s c rib e d by them . However, i t i s a p p a re n t t h a t c a p a c ito r s o r tra n s fo rm e rs made w ith o u t PCBs w i l l be l e s s f i r e - r e s i s t a n t th an p r e s e n t p r o d u c ts , th u s le a d in g to an undeterm inable in c id e n c e o f f i r e s , h ig h e r In su ran ce ra c e s , and a d d itio n a l p ro te c tio n f a c i l i t i e s . In the case of cap acito rs, the replacem ents are lik e ly to be la rg e r and le s s e f f ic ie n t, thus consuming more of th e re s o u rc e s re q u ire d In t h e i r m a n u fa ctu re. A more com plete i 187 in 070- ** -14 a n a l y s i s o f th e co n se q u e n ce s o f e PCB ben v e s d e v e lo p e d by th e G e n e ra l E l e c t r i c Company and a d d re s s e d to D r. M artha S a g e r, Chairm an, E f f lu e n t Stn& darda and W ater Q u a lity A d v iso ry C o m i t t e e , EPA (4 3 ) . Ve c o n cu r w ith th e G eneral E l e c t r i c Company's c o n c lu sio n s. Our purpose In con sen tin g on the proposed stan d ard s Is to aid th e Agency In th e developm ent of r e a l i s t i c e fflu e n t sta n d a rd s which w ill achieve the Intended o b je ctiv es w ithout serio u s te c h n ic a l, so c ia l,a n d econom ic d is r u p tio n s . Ve re c o g n iz e th e s e rio u s n e s s of th is endeavor and f in d a s ta te m e n t made by Mr. John R. Q u a rle s , J r . , Deputy A d m in is tra te Environm ental P ro tec tio n Agency, of considerable In te re s t. At a re c en t c o n fe re n c e , Mr. Q u a rle s (26) s t a t e d ; "Ve have found i t v i r t u a l l y Im po ssib le to d e v is e I n te llig e n t stsn d a rd s which sp ecify sn a p p ro p ria te degree of co n tro l over to zle p o llu tan ts Irresp e ctiv e of the sources of those p o llu ta n ts and fa c to rs a ffe c tin g the f e a s ib il ity and tim ing of th e ir b te a e n t . The d if f ic u l tie s which could be a n tic ip a te d in e sta b lis h in g e fflu e n t s ta n d a r d s were re c o g n iz e d by th e N a tio n a l Academy o f S cien ce in i t s p re p a ra tio n of Water Q u a lity C r ite r ia , 1972. In a review which appeared In th e Environm ental R ep o rter (38) dated August 24, 1973, the fo llo w in g p e r t i n e n t s ta te m e n ts h ig h lig h t some o f th e a re a s o f co n cern : "Knowledge o f lo c a l enviro n m en tal c o n d itio n s i s e s s e n tia l p rio r to a p p lic a tio n of any w ater q u a lity reconm endatlons fo r m arine aquatic l i f e and w ild lif e ..." "NAS s a id a p p l i c a t i o n o f recom m endations to a l o c a l s itu a tio n is unique beesuse i t re q u ire s an under' standing of the c irc u la tio n of w ater and the re su lta n t m ixing and d i lu tio n o f p o llu ta n ts , a knowledge of b io lo g ic a l sp ecies snd determ ination of the most se n sitiv e sp ecies, snd an evaluation of the tra n sp o rt of s ta r la is through th e food web." "NAS s s ld i t I s n o t p r a c t i c a l to make recom m endations fo r the re la tiv e ly p ersiacen t organic p o llu ta n t based on w ater c o n c e n tra tio n , e s p e c ia lly when p a r t i t i o n S c o e f f ic ie n ts a re unknown." % r* E n ro ls 188 lo o T o n 15- Vo.can a p p re c ia te H r. Q uarles * co n cern , p a r tic u la r ly as i t a p p lie s tc K S i. Lacking good s c ie n tif ic in fo raa e lo n on th e fe e s and e f f e c ts o f FCBa i n com plex w a te r sy stem s each h av in g u n iq u e c h a r a c t e r i s t i c s , we urge extrem e care be tak en to avoid th e prom ulgation of e f f lu e n t stan d ard s which are u n a tta in a b le and unw arranted. i Subscribed and sworn to b e fo re na th is V. B. Fapageorge. i . r k/ _ day / My Commission e x p ire s Fnoi?40 189 L W. B. Fa p a g s o r g e B2SK De ce mber 9, 197* PCEs - M i n u t e s o f M e e t i n g w i t h NIOSH - 1 1 / 2 2 / 7 * /f E. P. W h e e l e r - - A2A ce H. S . B e r g e n F. J. F itzg erald Robert F l i n t - 17*0 D. B. Ho sme r Clarence Sweets *--f O G. L. B r a t s c h W. C. Engman ^ r r .. 1 7 ^ 0 G. F. F o r t R. E. K e lly G. J . L e v i n s k a s J . R. S a v a g e T h e m e e t i n g wa s h e l d a t t h e r e q u e s t o f J o s e p h K. W a g o n e r , S. D H y g D i r e c t o r , D ivision of F ield S tudies and C lin ic a l I n v e s ti g atio n s (DFSCl), National I n s t i t u t e fo r Occupational Safety a n d H e a l t h ( NI OSH) . NIOSH r e p o r t s t o t h e C e n t e r f o r D i s e a s e C o n t r o l (CDC) i n t h e D e p a r t m e n t o f H e a l t h , E d v * * t i o n and W e l f a r e (DHEW). The p a r t i c i p a n t s i n t h e d i - : . , : i ; n a r e a s shown in the a tta c h e d l i s t . The o r i g i n a l p u rp o s e was to e x p lo r e w hether Monsanto had a "suitable occupational group fo r study" to assess the p o t e n t i a l c h r o n i c e f f e c t s o f PCBs. To be i n c l u d e d w e re ^PCB'rexposed a c t iv e and in a c tiv e workers a t Monsanto in a p l a n n e d r e t r o s p e c t i v e c o h o r t s t u d y . " What t h i s would i n v o l v e i s o b t a i n i n g w o r k h i s t o r i e s o f t i m e s p e n t i n PC3 d e p a r t m e n t s , and medical re c o rd s of a c tiv e and s t i l l - l i v i n g in a c tiv e employees. ' I h e stu d y would no.t be com plete w i t h o u t e x am in a tio n o f d e ath r e c o r d s o f t h o s e nP C 3 - e x p o s e d " e m p l o y e e s who a r e d e c e a s e d -- i n c l u d i n g t h o s e who e x p i r e d w h i l e e m p l o y e d a n d t h o s e who expired a f t e r term in atio n o f employment because of retirem en t o r fo r any o t h e r cause. The p r o p o s e d s t u d y was s t i m u l a t e d b y a r e p o r t f r o m Dr . K i m b r o u g h , T o x i c o l o g i s t , CDC, t o NICSH, t h a t s h e h a d f o u n d a n alarming r a t e o f l i v e r cancers in r a t s fed Aroclor 1260, B r i e f l y , she found 15 o f 180 fem ale r a t s with " d e f i n i te h e p a t i c c e l l c a r c i n o m a " when f e d A r o c l o r 1260 a t 100 ppm i n t h e u i e t f o r 22 m o n t h s . On l y o n e o f 173 c o n t r o l s h a d t h e carcinoma. She then described a number of o th e r l i v e r tis s u e e f f e c t s as "pre-can cero u s le s io n s " and found these in 175 o f the experim ental r a t s and in dnly three of the c o n tro ls. ) F,oni94i 190 000043 I . ' WesTlnghouse Electric Corporation / i I ; i *i e ' i FEB * t<i7$ f\ * '%t Soutn Baron 0mriGut;c;i f.' jns'ctntr Boisn 5!W*st Soutn Boston vuitmu 24592 it q jis t s w i February 3, 1975 t - 1 Dr. V. B. Papageorge : Manager Environmental Control Honaanto Coopany Organic Chemicals Division 800 North Llobergh Blvd. S t. L ouis, M issouri 63166 Dear Dr. Papageorga: Attached you v l l l fin d a l i s t o f quastlons th a t have been askad by our employes reg ard in g the use o f In e rte e n . Mr. Carry Wilburn, our Engineering Manager, f e l t I f th ese questions could be answered you would be the man to answer them. Ve have h a d ,In tha p a s t ,workplace meetings w ith our employes e x p lain in g proper use o f In e rte e n and t a i l i n g them u n less I t is consumed, i t p re se n ts no r e a l danger to them. I n answering th ese q u e stio n s, h o p efu lly ve w ill gain much needed knowledge on In e rte e n and how to p rasan t i t proparly to our employes. Thank you fo r your h e lp . Very tr u ly yours, Dad A. A lbert S taff Supervisor Personnel le la tlo n i c c : George Bvlxdoa, Marvin Bowling WBAN 0 0 0 0 2 6 F.00!?42r ~ > W 191 ` ' V 1 Q uestion: Does In e rte e n hive permanent e ffe c t on the human body? I f w , what type o f permanent damage and how long a period of tim e doe i t tak e fo r chi to develop? I f n o t, explain whv i f possible, 2 . Q uestion: Several hourly employes have mentioned re c e n tly chat many chemicals such as Inerteen cause s te r iliz a tio n a fte r a prolonged use. Is th is true? 3 . Q uestion: Since In e rte e n e ffe c ts b ird s end o th e r anim als, i f th ere i s no r e a l e f f e c ts to human b ein g s, how do you explain i t to employes In such a way th a t they w ill understand why I t ean k i l l a b ird and not a human? 4 . Q uestion: I f an es?loye s p i l l s In e rta a n on h is c lo th in g and l a t e r ta k e i the c lo th in g home to ba vaahed w ith ocher clo ch es, v i l l th is have any e f f e c t on he o r h is fam ily and should he carry hla clothea hone be be vaahed? 5 Q uestion: * Ea^loyea c arry In e rte e n home on th e so le s o f th e ir shoes end complain q u ite a b it about th a a ffe c t In erteen haa on wearing o u t t h e i r shoes. Is th is a serious problem? W ill In erteen in th e so le s end le a th e r o f shoes, over e long period of tim e, have an e ffa c e on th a fe e t and sk in sin ce th e shoe is the only p ro te c tiv e equipment we wear on our f a s t and the In e rte e n penetrates through tha le ath ar. 6 . Q uestion: There l a ona employe in our plane who had no problem whatsoever w ith In e rte e n years ago. A fter s ix y ears of using, now when he works in In e rte e n (which la a p a rt o f h is Job) ha davelops a sw ellin g on the in n e r bicep o f h is l e f t arm, only in one lo c a tio n . Could th is be from In e rte e n o r not? I t goes away as soon ai he gets out o f the In e rte e n . I t is sim ilar to the sv ellin g a fte r taking an in jectio n . 7. Q uestion: Are th ere hand cleaning solvent m aterials th a t va should be using when working in In e rte e n to coee our skin befors working l a I t and to wash i t o f f a f t a r we fin is h working in it? P lease give your recocm endatlou. Our employes working in In e rte e n are not able to use gloves since i t is an assembly a r e a . Evan i f they could, tha In e rte e n would destroy pha p ro tectiv e glove. SuaMiry: I f th e re are any q u estio n s we have not brought up th a t you are avara o f , p lease Include in your cocnenta, or any ocher Inform ation you ean give ua concerning the proper use of Inertaan. Enmwa 4 BAN 0 0 0 0 2 7 192 Monsanto M O M iA irro in o u s t k a i n n r n 00 N liAJMl'f* lotnr>r# St. M itu ri I3 t t * : 3I4J 4 > I0 0 0 ico. j^ ou.h'4 mocax February 26, 1575 Mr. Dan A. Albert Staff Supervisor Personnel Relations Vestinghouse Electric Corporation Box 290, Highway 53 '.Vest Sc.th Boston, Virginia 2^*592 Dear Mr. Albert: I have received your letter dated February 3 asking us to respond to a list of questions. Since these questions relate to human health considerations, I have asked our Medical hearing Dferpoamrtuamensthorttolyp,repeairteherthefrormesrpyonsoef.ficeYouorshforuomld be a representative of our Medical Department. If I can be of further service please let me know. Sincerely, VBP:pd V. B. Papageorge Manager, Product Acceptability Specialty Sc Process Chemicals (( ( W tM M t f GN 00002a lorn ? m 193 Monsanto MT WtifCT ('((Ci TO V W. B. Papageorge lurch 18 , 19 75 S t. Louis_________ BSSX C. Paton E. P, Wheeler Vootfc Attached la the o r ig in a l o f a l e t t e r addressed to Mr. Dan A. A lbert o f W estinghouse, South B oston, V irg in ia . The co n ten ts o f t h is l e t t e r have been review ed with Dave Wood and i t was agreed th at the l e t t e r be d e liv e re d b7 you p e r so n a lly to South Boston, g iv in g you an opportunity to d iscu ss w ith the Westinghouse rep resen tatives the proper approach that must be taken in presenting th is Information to avoid undue concerns and m isunderstandings. W ill you p lea se d eliv er th is le t t e r as soon as p r a c tic a l. W. B. Papageorge /pd * w . 1 a t v . I'T> GBRN 0C1640 194 C C i Monsanto wonunto mourmuu. ctsincAU c a 100 N. Lindbergh loglavir Sl. Louit. Mmen S3I6S Phon: OM) M4-1000 .JW&crra mocBBocxou mmm March 18, 1975 Mr. Can A. A lbert S ta ff Supervisor Personnel Relations Vestinghouse E le c tr ic Corporation Highway 53 V est South Boston, V irgin ia 24592 Bear Mr, A lb ert: Attached are responses to the questions lis t e d In your l e t t e r dated Pebruary 3* 1975. In addition to the Industrial hygiene practices described in our responses to your qu estion s, I cannot overemphasize the need to p rop erly co n tro l the use and handling o f In erteens to prevent th e ir escape Into the environment. A lso, In d iscu ssin g th is Information with your employees, Z str o n g ly reconaend th at the p ersp ectiv e gained from over AO years o f exp erien ce In which no human harm has r e su lte d , be emphasized. In summary, the proper handling o f Inerteens should pose no environmental or human h ealth problems, perm itting s o c ie ty 's continued use of a very valuable m aterial. .. _ . . _ .. ..... ... .. I hope the above Inform ation Is u sefu l to you. I f 1 can be o f fu rth er s e r v ic e p le a se l e t me know. S in c e r e ly , , ** ___ j j V. B. Papageorge Manager, Product A ccep ta b ility S p ecialty & Process Chemicals VBF:pd u-PtINTIFF'S bil .^E XH IB IT ;: -y- a nuli al Vanitala Cim, i *t K o n i? 4 6 G3RN 0 0 1 6 4 1 . 164 1 . Q u estion : Does In er tee n have permanent e f f e c t s on the human body? I f so , what type o f permanent damage and now long^ & p er io d o f time does i t take fo r t h i s to d evelop ? I f n o t, ex p la in why, i f p o s s ib le . The p o ly c h lo r in a te d b ip henyls i n In erteen can have permanent e f f e c t s on th e human body. The le n g th o f tim e or period o f exposure n ecessa ry to develop symptoms depends on the degree or amount o f exposure. In general a s in g le exposure for a few minutes to atmospheric concentrations* th a t cause i r r i t a t i o n to the eyes and/or r esp ir a to r y tr a c t would not be expected to cause e ith e r the skin eruptions or demonstrable l i v e r In ju ry. She problem a r is e s from repeated and prolonged exposure to atmospheric concentrations in excess of the accepted T hreshold Lim it L evels or repeated and prolonged skin co n ta ct. . The p o ly c h lo r in a te d biphenyls have not been recognized as skin ' 'i r r i t a n t s 11 in th e same sense th a t c a u stic m a teria ls or many organic chem icals are ir r ita n ts . Because of th e ir "solvent" a c tio n in removing the n atu ral f a t s and o i l s from the sk in , le a c h in g , drying arid chapping, repeated and prolonged skin c o n ta ct should be avoided. When th e p o ly c h lo r in a te d biphenyls are mixed w ith other c h lo r i nated hydrocarbons, the mixture may be c l a s s i f i e d as a Bkin irritan t. The p o t e n t ia l t o x ic e f f e c t s in humans from e x c e ssiv e exposure to p o ly c h lo r in a te d biphenyls in clu d e in ju ry to the l iv e r and ch loraen a. In anim als, the l iv e r e f f e c t i s demonstrated by In creased l i v e r w eigh ts and in ju ry to c e llu la r t is s u e . Although ch loracn e i s d i f f i c u l t to evalu ate in anim als, in humans, th is take th e form o f comedones (large blackheads w ith ty p ic a l acu*e p u s tu le s ) and may be an e x te rn a l symptom o f over exposure pre ceding serious liv e r injury. Animal data and human experience in d ic a te th a t the to x ic e f f e c t s are s im ila r whether exposure r e s u lts from in g e s tio n , Inhalation o f vapors, or absorption of the liq u id m aterial through the unbroken skin. (See AIHA h y g ie n ic Guide S e r ie s - "Chlorodiphenyls" a tta ch ed .) 2. Q uestion: Several hourly employees have mentioned recently t h a t many chem icals such as In erteen cause s t e r iliz a t io n a fte r prolonged use. Is th is true? There Is no evidence that polychlorinated biphenyls cause " s t e r iliz a t io n " i n humans. t,bRh OQlfc*2 165 j ) 3 Q uestion: Sin ce In er tee n e f f e c t s b ird s and o th er animals i f th ere I s no r e a l e f f e c t s to human b e in g s, how do * you e x p la in i t to employees in such a way th a t they w i l l understand why i t can k i l l a b ird and not a human? There i s a p o t e n t ia l r e a l e f f e c t to humans - in clu d in g death as discussed in the answer to Question 1 . IXie to d iffe r e n c e s in metabolism o f food (and food contami n a n ts) in b ir d s and humans (and p a r tic u la r ly the d ifferen ce in th e rep rod uction p ro cess in b ird s and mammals - in c lu ding humans), b ir d s are p a r tic u a lr ly s e n s it iv e to many chlorinated hydrocarbons including polychlorinated biphenyls. Q uestion: I f an employee s p i l l s In erteen on h is c lo th in g and l a t e r ta k es the c lo th in g home to be wa ed with other c lo t h e s , V i l l t h i s have any e f f e c t on he or h is fam ily and should be carry h is c lo th e s home to be washed? There should not be 'any e f f e c t on an employee or h is fam ily from home laun dering o f work c lo th in g . I f washed v;ith other c lo th in g , there nay be residual odor of the chlorinated hydrocarbons in the cloth in g. 5. Q uestion: employees carry In erteen home on the so le s o f th e ir shoes and complain q u ite a b i t about the e f f e c t Inerteen has on wearing out t h e ir sh o es. I s t h is a se rio u s problem? V i l i In erteen in the s o le s and le a th e r o f shoes, over a lon g p eriod o f tim e, have an e f f e c t on the f e e t and skin s in c e the shoe i s the only p r o te c tiv e equipment we wear on our f e e t and th In erteen p en etra tes through the le a th e r . There should not be p o ly ch lo rin a ted biphenyl on the flo o r fo r workmen to contam inate t h e ir shoes to carry home. The p la s t ic iz e r or solvent action w ill destroy or shorten the lif e o f th e sh o es. More Im portantly, the wearing o f contaminated shoes could lead to absorption of the liq u id through the so les o f the f e e t a s through any other unbroken skin surface. 6 . Q uestion: There i s one employee in our p la n t who had no pro blem whatsoever with Inerteen years ago. After six years o f u s in g , now when he works in In erteen (which Is a part o f h is Job) he develops a sw ellin g on the inner bicep of h i s l e f t arm, on ly In one lo c a tio n . Could t h is be from In e r te e n or not? I t goes away as soon as he gets out of th e Inerteen. I t Is sim ilar to the sw elling after taking an In jectio n . inM ?48 GBAN 0 0 16*i 3 166 We do not b e lie v e th e re can be any a s s o c ia tio n between a s w e llin g on th e in n er b ic e p " o f the arm and exposure to polychlorinated biphenyls. 7 , Q u e s tio n :. Are th e r e hand c le a n in g so lv e n t m a teria ls that we should be u sin g when working in In erteen to coat our sk in b e fo r e working in i t and to wash i t o f f a f t e r we f i n i s h working In i t ? P lea se g iv e your recommendation. Our employees working in Inerteen are not ab le to use gloves sin ce i t i s an assembly a rea . Even i f th ey co u ld , the In erteen would destroy the protective glove. We assume the q u e stio n r e fe r s to the use o f "Barrier Creams" r a th er than a "hand cle a n in g so lv e n t" . There are a number o f b a r r ie r creams a v a ila b le to p rotect workers a g a in s t w ater in s o lu b le s o lv e n ts . Probably the most e f f e c t i v e in clu d e s ilic o n e "to provide an impenetrable sh ield " . A problem w ith such creams I s th a t th ey may o f f e r a f a ls e sense of security. Proper use in clu d es a d is c ip lin e which req uires lib e r a l a p p li c a tio n a t the b egin n in g o f a v/ork s h i f t and a f t e r each washing t o f the hands during the work day. 1001 liBRh OGlo** 167 s < ji H Y G IE N IC GUIDE SERIES Chlorodiphenyls (Containing A2% *nd 54% Chlorine] /w \ O * (x + y - 3 or 5) SignAunt Physical Proportias1 The ehlotodiphenyli i n light itnw ^olorcd mobile (42% chlorinated) tad vueoui (54% chlorinated) liquid with typical chlorinated aromatic odors. The** compound a n chlorinated to ipeeific weight ot chlorine. Chlorodipbenyl (42%) contain 42.0 -- 0.5 chlorine, an amount eoim pondinf to three chlonnc atom in unuaigncd poaitioiu. Chlorodiphenyl (51%) contain* 54.3% chlorine corresponding to five chlonnc atom in unauignrd petition. Both compound are iiuolublc in water, but io)ubU in bcnaeae, iaroacae, acetone, amyl alcohol, ether and cUaraiorei. C kfdipktm jt (42%) CkUrJipknjri (34%) W olecula/ w eight: 247J3 326.45 Flaih m ini (Cleveland O, C .): 176M80*C (S49*-355*F) None Diatillaiion ranee: 325MW C JM '-S S O 'C tp o d ic gravity: 1.381*1.392 (23*/15J*C) 1.495*1.505 (65V15J*C) Vapor prm ure: 0*C 0.001 mm 0.00006 mm U*C 0.006 sua ( t) 0.00054 mm (n i) 150*C 200*C 2T0*^m 1.4 mm .0 BS At 23*C and 760 mm Hg: iaturaied air contaia 0.080 mg/titer 0.009 mc/l>tcr 1 mg/liicr = M .l ppm 0,010 mg/lioff 74.9 ppea 0.013 mg/liicr I. Hyi'iMk Slutdirdi A. UxOOMMBMOtS MAXIMAL ATMOSnHCXlC ooMCXMTXATtOMa (8 hours): One millu (run chlorodiphenyl (425) per cubic meter o{ air and 0J milligram chloro- diphenyl (545) per cubic meter of air.1 This is based on the results of The C a ra iM totow a tw * M p Ja j w w wiw^to lh t. aMm. St Ll ol Xt oifaaa aa..*.....O...U..a..wvJA*T e to ] t o T. C e m oaiWw tof fmt ito i wCiia atoiwStowto w q to ika chronic anim al inhalation studies.1 B. Sh m t u p o s u u tulmance: Ten mg o f a diphenyl of unspecified chlorine content per cubic meter of air has been reported as unbearably irritating.* C Atm o a r mrate coNCZNTunoN immcih. a t il t itASAaoous to life : Not known for man. Irritatio n of the eyes, note and throat at levels which have not caused acute illness preclude the likeli hood of voluntary exposure to immedi ately hazardous concentration. FiX V * ? * 5 0 GdRN O O l o O 168 januery-Febntary, 1965 - II. Tnise fro p irtiti A . I n h a l a t io n : Experim ents w ith ch lo ro diphenyl (4 2 % chlorine) 'rere run at concentrations of 8.6 jig /lite r and at 6.83 > if/lite r o f it r . C a u , m ice, rabbits and ra u were unaffected by the higher level w h ile . guinea pigs showed poor grow th after seventeen 7-h o ur/d ay ex. poaura over 24 days. Eighty-four 7n o u r/d ay.ec p o s u ra at the low er con. centration had essentially no effect on sim ilar species of anim als.1 In the ease of ehlorodiphenyl (545 chlorine) eighty*three 7-h o ur/d ay ex* pceures over 121 days to a concrestration of 5.4 AMg/Iiter resulted in in ju ry to liv e r re lit and increased liv er weights in rats. A t a concentration of 1J pg/1iter fo r one hundred and fifty 7-hour/day eepovures o ver 213 days, the rats showed distinct microscopic changes in the liver.* T h e literatu re contains many refera c ts to the potential toxic effects of chlorinated diphenyls in man and ani mals. T h e early w ork included investi gations of chlorinated naphthalenes, c h lo r in a te d d ip h e n y ls , chlorinated d iplienyl oxide and various m ixture! of these. A a early report indicated serious toxic effects from ehlorodiphenyl chlorimated to the o tten t of 6 3 $ .* A later report by the principal author properly identified the earlier sample as a m ix tu re o f chlorinated diphenyl and chlori nated diphenyl benzene.* How ever, only a few authors of subsequent papers, bul In in s o r textbooks have noted this cor rection and the original data are cited repeatedly aa relating u chlorinated dip h ay h aio n e. . ' B- S c a r co nta ct: Both compounds are read ily absorbed through the dipped, intact akin of .rabbits. T h e m inim um leth al ioat when the undiluted oiatc- ria k w ere applied to the covered tS p p cd , m tact skin o f rabbits fo r 24 b e a n was approxim ately 1.0 cm A g for th e 42 % chlorinated and 1-5 g m /kg for d ie 3 4 % chlorinated.* Local action on the skin is sim ilar to th a t o f common organic (ven ts where contact leads to removal o f natural fa u and n ib w ith subsequent drying and o m ebag of the skia. H um an cases o f chloracnc have not been reported from the uie of these -two tpccific chlorodiphenyls. The potential undoubtedly exists because of <--- which were reported from the use of chlorodiphenyls with a higher chlorine content and from mixtures with other chlorinated aromatic compounds.M ** C . E rt c o n t a c t : The liquid products and their vapors arc moderately irritating to eye tissues. D . I n o u t io m : T h e acute oral toxidties of the undiluted compounds are not great as evidenced by oral L D M's in rau of approxim ately 8.63 gm (7.61 to 9.78 gm ) per kilogram for the 42% chlori nated and 11.9 gm (10.48 to 13.45 gm l per kilogram for the 34% chlorinated.* C entral atrophy of the liver appears to be the chief toxic effect. III. Industrial Hygiene Practice A . Ix o c m tiA L vacs: The chlorodiphenyls are used as dielectrics for condensers, capacitors and transformers, plasticizers is synthetic resins, in emulsion adhes ives, as nonflammable hydraulic fluids and aa transfer media. B. Ev a lu a tio n o r sxro svaas: 1. Air tempting and enelynt: a. D irect field mediods: None b. Laboratory methods: (1 ) Collect in secondary butyl alcohol in fritted bubbler or tw o Urge unpingen in scries; concentrate sample and complete analysis by one o f various methods for chlo rinated hydrocarbons.*. (2 ) Sample a ir through com bustion furnace, collect chloride ion from decom posed e h lo ro d ip h e n y l in suitable alkaline solution and determine chloride ion cone n tra tio n .' C. H aXAXOS AND TMCia UCOKUtNOU cokteol: 1. JnkeUiion: Absorption is chiefly by inhalation. Concentrations in the w orknw m atmosphere dwuld be m aintained below the recommended levels W here the chlorinated diphoiyls are used at mom tempera* Earn . brn o 0 1 6 '*6 169 Jonuary-Fcbruary, I9C5 tuna, the hazard of inhalation is considered slight or absent. When iheae materials are subjected to devated temperatures, the process either should be completely enclosed or other adequate mechanical ex haust venuLanon must be provided to reduce concentrations to a f e levels. In heat transfer media appli cations, the system must be designed and constructed so that it is leakproof. Special gasket materials and pump seai< are available to prevent leakage. T he reservoir tank should be airtight except for a vent to the outdoors. In the e v e n t of spills or leaks of Sot fluids, use chemical cartridge respirators or gas masks approved by the U. S. Bureau of M m for protection againjt organic vapors. These will provide good protection up to the concentrations shown on the approval labels and the odor will give ample warning if it co m a through the device. 2. Skin contoct: Operations and handl ing p roced u m should be such as to avoid the possibility of prole nerd or repeated skin contact. Contaminated clothing must be laundered before reuse. 3. E yt contact: Ere protection should be used where there u a potsfoiliry of liquid splashes. 4. Ingertian: In grin cm of these m ate rials a not a problem in industry. 5. Fire and explosion: The chlorodiphenyls are fire-resistant or essenti ally nonflammable liquids. When capxmd to flame or hot air faces they mav decompose to form CO, CO*, HC1, phenoiics and aldehydes depending an the temperature, avail ability of oxygen, area of the heated irface, rate of application of the liquid to the surface and other w ia b k s . IV. Medical U/armetien A. Em uccmcy TntATutwT: Skin surfaces g posed to chlorodipiienyls should be thoroughly washed with soap and water at osce. If clothing has been coo Lami nated' it should be removed promptly If exposure to a high vapor concen tration occurs, as in the case of spills at elevated temperatures, the patient should be moved from exoosure and kept at rest unol ieen bv t phvsician. Oxygen should be administered if breathing ts difficult. Eyes contaminated with chlorodiphenyl should be irrigated with water for at least 15 minutes and the patient should be n by a physician. Depend ing on the amount of inflammation and pain present, drugs like Com m o m * ointment and topical Pontocaine* may be indicated. B. S n c u i. r a o c m u R is : Persons who are regularly or repeatedly rrposed to chlonodiphenyls should be examined periodi cally to detect early evidence of skin im iio o n an d /o r liver damage. Persons with known liver disease should not be exposed to repeated contact with the chlorodi phenyls. V. Reference* 1. Monsanto Company, Organic Chemi cals Division: Tech. Bulletin # PL-306, ArocLer P U stic u m (Dec. 1960). 2. American Conference of Governmental Industrial Hygienists: Threshold Limit Values for 1964. A M A Arch. Em-iron. H colt It 9: 545 (1964). 3. Troon, J. F., F. P. Cleveland, J. Cappcl, and R. W Atchley: The Toxicirv of the Vapors of Aroclor 1242 and Aroclor 1254. Amer. Ind. Hyg. Assoc. Quart. 17: 204 (1956). 4. Elkins, H. B.: The Chcmutry of Indus trial Toxicology. John Wilev and Sons, Inc., New York (1959). 3. Drinker, C. K., M. F. Warren, and G. A. Bennett The Problem of Possible Systemic Effects from Certain Chlori nated Hydrocarbons. J. Ind. Hyg Too. t ifW. 19: 283 (1937). 6. * Drinker, C. K .: Further Observations on the Possible Systemic Toxicity of Certain of the Chlorinated Hydrocar bons. /. Ind. Hyg. Toxicol. 21: 155 (1939). 7. Wheeler, E. P.: Personal Communica tion, M o n an io Company, St. Louis, 8. GMriesesonubruirg6.31L6.6t. M. R Mavers. and A. R. South: The Systemic Effects Result ing from Exposure to Certain Chlori nated Hydrocarbons. /. Ind. Hyg Toxicol. 21: 29 (1939). 1(1012 ^ 2 BUN 0 0 1 " ? 170 HYGIENIC GUIDES COMMITTEE C. f . CAAPivTlfc, C k o rrm o m N. E. Boltov L LCumu J. IV. C l a y t o .v H. 1 . Elxins P. D Ha l u t Mask H rrt J. A. Ho uo * t o v D. JL M c F ti J. M. M c N u n i y , Ja. J. E. h r u i o R J. I. OuiM.YIMKI E. A. P rrrx ta U. C. PoXXANt X- L. Ralxkn W. L. S uttow X. C. Wanox G. L WtLXOK Hri'cnic Guide been n u r be obtained from die amuicav ivoveTLLU. ro ic k t a*ocla- noM, 14125 Prevent. Detroit 27. Michican. ai 23 rent each for rwopwe reprum; 30 cenu racn for four-pafe reprint. 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