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-I AR226-2762 Zm I* du Font da Honours and Coopany Haslcoll Laboratory for Toxicology and Industrial Medicine E lk to s Road, Hswsrk, Delaware 19711 HASKELL LABORATORY REPORT MO. 205-81 Material Tested ' Octanole add, pentadecafluoro-, ammonium salt* ' Haskell Ho." 12,037 Study Initiatsd/CosplsEed 2718/80' - 5>23>80--- Material Submitted bv W BSBBFl-------- Polymer Products Department Washington Works sobacpteIIHHALATIOH TOXICITY OF PgWTADECArLDOROOCTAHOIC ACID. AMMONIUM SALT Introduction' Pentadecafluoroobtsnoic add, ammonium salt (C~8i H H has prevlousl^eg^ahown to be highly toxic to rate by Inhalation cRLC - 4 .8 "S' ard to u s e x significant enlargement of the User. An inhalation subacute e t t i d y ^ P H B M y performed at 11 and 83 mg/m" caused liver degeneration, enlarged liyera and increases in liver enzymes atboth concentrations. A recent subacute dermal study with r a t s a t 20 200, and 2,000 ug/Kg/day for lO; days had similar findings a^al^dosSi along * with elevatad blood fluorlda throughout the 54 day test. The purpose of this subacute Inhalation study with rats at 0, 1, 8. and 80 ag/rn was three fold: ; *' 1. attempt to achieve a 'no observable effect" concentration 2. correlate liver pathology, blood organofluoride and blood serum _ enzyme changes with dose and time 3. hold animals for prolonged observation to determine reversibility of effects. ' General Protocol Six-week old male Crl:CD fats were housed 2/cage in stainless-- steel wire mesh cages and provided Putina Certified Rodent Chow #5002 and water ad libitum. Prior to exposure .^tS were quarantined for 10 days to assure they" exhibited no overt signs of disease and a normal race of growth. Rats were tested at 7-8 weeks of age - weighing 240-279 g. Design concentrations of C-8 were 0, 1, 8, and 80 mg/m" for Groups I, II, III, and IV, respectively. Three groups iof 24 rats were exposed to dust atmospheres -I Company Sanitized. Desnot contain TSCA CBf 001 of C-8 (II, ill, and IV), while an identical control group (I) was simultaneously exposed to air only* Group I and ZZ were contained in one high velocity hood, Group ZZZ and IV in another* Group I was handled with clean gloves during each loading and unloading. All groups were restrained in wire mesh holders and exposed head-only In SO 1 glass chambers for 6 hr/day, S days/wk for 2 whs (excluding weekends)* During exposure rats were observed and clinical signs noted* Post-exposure, rats were weighed and observed dally for 14 recovery days, then weighed and observed twice/vk through 64 days recovery. By design 5 rats/group (until fewer than 5 remained) ware sacrificed at 0, 14, 28, 42, and 84 days recovery, for a total of 96 test days* Generation Procedure Dust atmospheres of C-8 wpre generated by passing air through a glass generator (2 or 3 stages, depending on desired concentration). An electric motor and steel rod with plastic paddles agitated the first 2 stages, if necessary to achieve the desired concentration. Analytical Procedure Two types of analytical methods were used to monitor C-8 concentrations during exposures. ! For the high concentration (80 mg/m3), chamber atmosphere concentrations were primarily determined by gravimetric analysis. Known volumes of chamber air were drawn through preweighed Gelman glass fiber filters, Type AE, 47 as at 2 1/min. Samples were taken once per hr. for 30 to SO mlnuees. Concentratlons were determined from weight gain- (mg) of -the fi-l-ter/1 of chamber air. During each exposure samples from this chamber were also analyzed by wet chemical analysis (below) in order to cross-check the methods. For the first six exposures 2 1 samples were taken each hr. Fcr the last 4 exposures two of the filters from the gravimetric analysis were cho-en to be analyzed. The C-8 was eluted from the filter as described below. For the intermediate and low concentrations, chamber atmosphere samples were collected tee per hr (15 1 for intermediate, 100 1 for low) on Gelman glass fiber filters, but weight gain could not be measured* A wee chemieal analytical method* was used instead* This consisted of dissolving the C-8 from the filters into acidified aqueous methylene blue solution. A colored complex forms which is extracted into a nonpolar solvent (e.g., chloroform or methylene chloride). Concentrations of C-3/methylene blue complex were spectrophotometrlcaliy determined 650 nm end chamber concentrations were determined by comparing to standards prepared dally. A Sierra Cascade Impactor Model #2i8K Eight Stage was used to determine particle size. Company Sanded. Does not contain TSCAC84 -2 002 Clinical Chemistry Protocol Following the tenth exposure (0 daye recovery) and recovery daye 14, 28, 42 and 84 blood was tkan frbm the calls of 5 rats In each group. Measurements of alkaline phosphatase (GOT) and glutamic-pyruvic transaminase (GPTjgWere made of the blood eertn. Details are in the clinical pathology report. Pathology Protocol Following the tenth exposure (0 days recovery) and covery days 14, 28, 42, and 84, five rats from eact group were sacrificed for Pthologic evaluation. At nacropay the rets were examined and organs ware saved for microscopic evaluation. w^ g h t s o f t h e Vungs, heart.thymus, spleen, liver, peetee, and ltidneys-were obtained. Details pathological indices are in thfe pathology report. Body Weight and Organ/Body Weight Analysis andMean body weights were calculated plotted to show growth curves of Groups I, II, H I . and IV fro 0 through 96 days on test. At each sacrifice mean organ weights (listed above) and organ to body weight ratios were calculated. Procedure for Analysis of C-8 in Rat Blood At necropsy approximately 8 to 10 ml of bipod was collated O n heparinized tubee) from each fat by cardiae puncture. The blooa was stored at 4*C until all samples were collected. Blood samples from Group# I and IV were analyzed at each recovery period. Blood samples from Groups II and III were analyzed only recovery days. _ Analysis of the blood was conducted Polymer Products Department, Experimental Station. Details appear in Appendix 4. Company Sanitized. Does notcontain TSCA CBI 3- 003 a Resulti: Exposure Time-Weightad-Averaga (TWA) concentrations and ranges are tabulated below. Comparison of the two analytical methods at the high evel demonstrated that the 2 1 samples, taken for wet chemical analysis, * a not ranresentstive of the 60-100 1 samples taken for gravimetric analysis. These samples tended to be lomar (12 to 45Z) than the gravimetric a" 1yai9- Jrect wet chemical analysis of filters used for the gravimetric analysis showed that the two methods uere comparable (wet method 6X lower than gravimetric). Exposure _____ Group II o. TWA.ng/m Range Group III TWA.mg/m Range Croup TV TWA.na/a j 21 0.1 0.4 0 0.2 0.02 1.2 6.7 10.7 0.5 - 10.5 11.0 5.5 - 21.9 83.5 17 - 167 44 148 3 4 5 6 7 8 9 10 1.5 1.0 1.6 1.4 1.2 0.9 1.0 0.4 0.4 2.8 0.7 1.3 0.7 3.0 9.0 8.9 10.0 0.2 2.2 0.5 1.8 7.3 8.1 0.5 1.4 7.5 0.5 2.0 7.6 0.1 - 0* / , 1.3 2.4 - 16.S 5.6 - 13.3 2.1 - 24.9 1.4 9.3 4.1 15.1 1.7 - 15,00.3 - 11.3 0.7 S 3.2 79.5 67.8 95.1 88.6 78.1 89.1 77.4 75.1 23 -- 136 45 115 63 ** 158 61 -- 160 61 97 62 -- 122 72 -- 86 67 94 i concentrations were: Croup Cone. (relative) Concentration, ms/m* + S.D,a II Low III Intermediate IV Hi*h i 1.6 + 0.5 7.6 + 2 . 5 83.9 + 12.8 Many attempts were made to determine particle size hut the particles did not behave typically. The information obtained from the high concentration chamber suggests the particles wire 1 to 2 u. The intermediate concentration chamber was analyzed during the $th exposure. Haas median diameter was 3.8 u* These data indicate most of the particles generated were respirable. Clinical Signs During exposures a high percentage of the rat# had slight to mild nasal and ocular discharge, which appeared to be dose-related. After the third exposure one rat In Group IV wae sacrificed "in extremis . During the fourth exposure one rat in Group IV died. Beth animals ware necropsied and tissues ware saved for microscopic examination. Rats in Groups I, II, and III showed moderate weight loaa for 1 to 3 days and sporadic weight loss throughout the remainder of the exposure and recovery periods. Three of 24 rats in Group had lung noise and all showed severs weight loss during the 12 day exposure period with sporadic weight loss throughout recovery. Company Saniliwd. D on not contain TSCACBi -4- O r-, (_) 004 Body Weight Analysis Mean body weight were evaluated statistically (Appendix 1). Group* I & II were not significantly 'lfferpnt. Group III waa not significantly different froa I and II u w il recovery day 5, when Group III weights were higher for 13 days. Group IV weights were significantly lower froa test day 2 through 16 (Figure 1). Organ Weight Analysis Organ/Body Weight Ratios Relative organ to body weight ratios for each group after each recovery period are outlined in Table 1 and Appendix 3. The dose-related changes Include Increased liver, lungs and tes.es weights. Liver/body weight ratios are depicted graphically in Figure 2. Other changes in organ/body weight ratios, were found (Table 1). Their relationship to compound administration is unclear. Mean Absolute Organ Weight Analysis Mean absolute organ weight analysis (Appendix 2) demonstrated findings similar to organ/body weight ratios (Table 1). However, this analysis appeared to be more sensitive, in that it: showed more dose-related changes in Group III, but this may be an artifact caused by an increase in Group III body weight? (which cannot be explained) accompanied by a normal increase in organ weights. J Other changes in mean absolute organ weights were found (Table 1). Their relationship to compoundj administration is unclear. ! Clinical Laboratory Measurements Elevated alkaline phosphatase (AP) activity was found in all groups exposed to C-B after 10 exposures (0 recovery), but only Groups III and IV were significantly different firom Group I. After 14 days recovery AP was elevated only in Group IV. After 28, 42, and 84 days recovery no differences were fotmd. - Pathology Macroscopic The morphologic changes observed at necropsy were varied. The only change considered to be compound-related waa hepatic (i.e., heavy livers). This occurred in 1/24 Group I rats, 0/24 Group II rats, 5/24 Group III r t s and 10/24 Group IV rats. This change was dose and recovery-time related. After 14 days recovery this change was not found in Group III and after 28 days was not found in Group IV. - 5 Ctopany Sanitized. Doe* not contain TSCA CBl 005 Microscopic Throe compound-related hlstomorphologlc changes wore observed* All were hepatic. These Include panlobular hepatocellular hypertrophy, eentrolobular hepatocellular hypertrophy and hepatocellular necrosis. All three lesions were observed In Groups III and IV but not in Group II. One lesion was observed In Group I. The presence of hepatic lesions was dose and recovery-time related as outlined below. After 28 days recovery all changes are considered to bs reversible in Group III and reversible by 42 days in Group IV. Humber of Rats with Microscopic Hepatic Lesions Recovery Day 14 28 42 84 Group I 0/5 1/5 0/5 0/5 0/4 Group II 0/5 0/5 0/5 0/5 0/4 Group III 5/5 1/5 0/5 1/5 1/4 Group IV 5/5 4/5 2/5 0/4 0/3 Cause of death could not be determined for the two rats that died or were sacrificed "is extremis" is Group IV. ' Blood Fluoride Analysis Blood fluoride was elevated in ell groups (including controls) 0 through 84 days recovery and was dose--related as shown on the table below. However, after 42 days recovery, blood fluoride in the controls was only 4 X above the limit-of detectability (0.007 ug) while Group IV fluoride was 250 X above. After 84 days recovery the control blood fluoride was only 2 X above background, while Group IV was still 120 X above. The presence of C-8 in control blood was probably caused by cross--contamination daring handling, exposure or housing. Recovery Day 0 14 28 42 84 Averase Concentration of C-8 in Rat Blood. usF/g Group I Group II Group III Group IV 5.3* 0.28 0.10 0.032 0.015 13 -- 1.2 - - 47 3.8 - - 108 10 . 7.1 1.8 0.84 * 1.4 excluding one high value Company Sanitized. Uoes not contain TSCA 006 Summary Pentadecafluorooctenoie acid, ammonium gait (C*8;[lj^k\ wftS administered to male CrlsCD rats by inhalation 6 hr/day, 5 days/wk for 2 wks a g / m ^ G r o i r i V ) 8 f (GrOUP X>* 1,0 (Growp XI>' 7,6 (Croup 1115` and 83.9 Observations of elinle&l signs during exposures showed only slight signs of dose-related toi^city (nasal and ocular discharge). However, at the high concentration after 3-4 days on test one rat died during exposure and one rat was sacrificed in extremis1*. Both of these rats were severely losing weight. Mortality was probably exposure-related although pathologic evaluation could not determine cause of death. The ocher rats in this group lost a significant amount of weight during the exposure period. Body weight analysis demonstrated no significant differences between controls (Group I) and Group II. Croup III body mights were significantly higher than controls from test days 17 through 33. Group IV body weights were significantly lower than controls from test days 2 through 16. Organ to body weight ratios demonstrated a dose-related significant increase in lung, liver and testes weights after 0 recovery days. The liver/body weight ratios mere significantly higher in Group IV through 28 days recovery. Mean absolute liver weights were significantly higlt- m Group III through 28 days recovery, but this may be an artifact caused by an unexplainable Increase in Group III body weights accompanied by a normal increase in liver weights. Clinical laboratory measurements demonstrated an increase in alkaline phosphatase (AP) inall groups exposedto C-8 after 10 exposures, which persisted in Group IV through 14 days recovery. Pathologic findings included a macroscopic liver change (heavy livers) and three types of microscopic liver lesions in Groups III and IV. Both findings showed a dose-response; relationship but were reversible by 28 days recovery (Group III) or 42 days:recovery (Group IV). Other charges were found (organ weights and pathologic lesions), but their relatioc_iip to compound administration is unclear. Blood fluoride analysis clearly demonstrated a dose-related presence of C-8 in all groups including the controls. The amount of C-8 in blood decreased with time, but was detectable after 84 days recovery in both controls and Group IV. Company Sanitized. Does not contain TSCA CBI 007 Conclusions " eitherr *lni" u* r*:1" '" ' or a ? ' 1" inhalation ior 5 mg/ demonstrated day. , w,,k ff.or ehe following: cwo week at e a no-effert concentration of 1 mg/3 for this study Exposure-rela tad mortality at 83.9 mg/3 An adverse effect on body and liver weight at 83.9 mg/m\ Elevateu seium alkaline phosphatase at 7.6 and 83.9 mg/m3 # "iCw 8COL1C 11Ver P * ^ o g 7 at 7.6 and 83.9 g/3 ?XlCJ*ffecta ^ 28 co 52 days recovery Of de parameters examined, blood fluoride analysis areved r k- itl. OOd poralster.t l o c a t o r of 2E.5T th* to C r6 u dl/fionlt no .id by io * Composition Contsminanta Synonyms: # C-8 U Jerfluorooctanoic cid, ammonium salt a Anaonlum perfluorooctanoate mi 1 Plastics Department M e t h o d , j j ^ ^ ^ ^ 88U8d i0/s/69> V Ib BA i * / ; Bfr^es; "Inhalation Toxicity offflMI iln :-ats, l H lZ*037 Clinical Pathology Report, August 13, 1980. P-I 3 ai-u;o3Ei"to"t" io!'-mo& *u*,! ^ ' & - 8- 008 Company Sanitised. o e s not contain TSCA & MRB:jrg Work by: Technician Supervised R.Mavis Brittelli Toxicologist ~ Study Director: _ Ladd W. Smith Pf- >r:j.rch Toxicologist Approved by: L^22Stf5eL. Gerald !.. K_e_nnj_ey^ Chief, Acute Investigations Section Company Sanitized. D esn ole0 iX a !iiT S C A C B f -- m 009 TABLE I CHANGES IN ORGAN/BODT HEIGHT RATIOS CCHANGES IN MEAN ABSOLUTE ORGAN HEIGHTS) Orsan Liver Group I II III IV 0 0 CO) 0 (0) + C+) + C+) Recovery Day 14 28 0 co) 0 CO) 0 C+) + C+) o co) o co) 0 c+) (+) 42 0 co) 0 CO) 0 CO) 0 co) __ 84 0 0 0 0 ((((0000)))) Lungs Kidneys I IT ITr IV I II ill IV o CO) m0 CO) o + C+) 0 CO) o CO) 0 c+) 0 CO) 0 CO) 0 co) 0 co) 0 CO) 0 CO) 0 co) 0 co) 0 co> o co) o CO) 0 (0) o CO) o co ) + CO) + (+) + C+) 0 CO) m0 CO) 0 0 CO) 0 co) 0 CO) 0 co) 0 CO) 0 0 ((00)) 0 CO) 0 (0) 0 (0) + CO) + (0) 0 (0) Testes I II III IV o CO) o C+) 0 C+) + C+) 0 CO) , o CO) 0 CO) 0 C+) 0 CO) o CO) 0 CO) o co) 0 CO) 0 CO) 0 CO) 0 CO) 0 (0) 0 (0) 0 (0) 0 (0) Thymus I II III IV o co) - CO) o CO) - CO) 0 co) 0 CO) , 0 CO) ; 0 co) 0 CO) o CO) 0 CO) o co) 0 co) 0 CO) 0 CO) 0 CO) 0 (0) 0 CO) 0 CO) o co) Spleen I II III TV 0 CO) 0 CO) 0 CO) 0 (0) ! 0 CO) 0 CO) 0 CO) 0 CO) 0 CO) o co) 0 (+) 0 CO) 0 CO) 0 CO) 0 (0) 0 CO) o co) CO) + 0 (c0+>) Heart I II III IV o CO) 0 (0) 0 CO) 0 CO) 1 0 CO) 0 CO) 0 co) 0 co) 0 CO) o CO) o (+) o C+) 0 CO) 0 CO) 0 CO) 0 CO) 0 + + 0 0 no d iffe re n ce fron control; + * increased t significantly different (p < 0*05 from control group by * * decreased t Dunnett and/or LSD* CO) CO) co) CO) - 10 - 010 oCompany Sanitized. Does notcontain TSCACB* CONTRO. GMHS LOT LEVO. <*NG/l> h* INI. LEVEL O H M NBA) HlCHlla 01 D in m HlWLSTf mcrmo figure 1 FC--143 BODY WEIGH! GROWTH CURVE [Mjlmaa 5' o li 41 IMVS QN TEST 11 - t* m m Figure 2 r> UH3oa3<n oiia iHSian Aaoa^aaAn 0 1 2 Company Sanitized. Does not contain TSCA CBi s' r;: -r r- 1-. v /. .. i'* " i i - IS - > -v. i,v< QQK09'an* ,ed.Os ' .../:., 1 BODY WEIGHT SUMMARY H* 12037 GROUP INTERVALS IN TEST DAYS * 1. 2. 3. 4. 5. CONTROLS LOU (.001 MG/L) INT (0.008 MG/L) HIGH (0.08MG/L) F RATIO(l) LSD(2) D U N N E T T (3) W M S (4) 255.3333 256.2083 259.3333 262.2273+ 2.276 5.7974 6.9919 99.5832 251.0417 248.2500 249.7500 243.7273+ 2.050 6.1575 7.4261 112.3369 252.3750 247.1667 251.3333 243.4545# 3.339* 6.2306 7.5143 115.0194 253.0833 251.5000 252.4583 238.0909* 8.656* 6.7015 8.0822 133.0623 256.2917 254.0833 255.9583 236.7273* 12.351* 7.3751 8.8946 161.1568 GROUP INTERVALS IN TEST DAYS 6 . 7. 8. CONTROLS LOW (.001 MG/L) INT (0.008 MG/L) HIGH (0.08MG/L) HF ^ F R A T I O (1 > LSD (2) D U N N E T T (3) U M S (4) 259.0833 254.8333 257.7500 237.9091#: 266.3750 261.9167 267.7500 253.4091# 12.264* 7.7290 ! 9.3214 176.9943 ! 4.721* 8.2386 9.9360 201.1031 270.0417 267.3833 271.7917 261.5909 2.094 8.5216 10.2773 215.1563 9. 10. 272.1667 270.5417 274.4167 258.7727# 4.698* 8.8888 10.7202 234.0999 273.8333 273.7500 275.666Z 253.954^) 9.724* 9.0707 10.9395 243.7791 GROUP INTERVALS IN TEST DAYS 11* 12. CONTROLS LOU (.001 MG/L) INT (0.008 MG/L) HIGH (0.08MG/L) 277.0417 274.6250 279.5833 254.8636# 275.6250 277.9583 283.5417 256.5909# F RATIO(l) LSD(2) D U N N E T T (3) U M S (4 > U.B49* 9.0440 10.9073 242*3445 13.711* 8.7298 10.5284 225.7984 - 14 - <vo^o .cO Qoe* Sa? CO' 014 CBV C APPENDIX 1 (c o n t'd ) (l1) RATIO OF AMONG- TO WITHIN-GROUP VARIATION-- O N E -FACTOR ANALYSIS OF VARIANCE. J(2> LEAST SIGNIFICANT DIFFERENCE-- GIVEN A SIGNIFICANT (ALPHA=0.05> F R A T I O r -J jY TWO MEANS DIFFERING BY MORE THAN THE LSD ARE SIGNIFICATLY DIFFERENT ITH A VARIABLE-WISE FALSE POSITIVE (ALPHA) ERROR RATE OF 0.05. (3> PUNNETT TEST-- AN Y TREATMENT MEAN DIFFERING FROM THE C u NiROL MEAN BY MORE THAN THE DUNNET-T -STATISTIC -IS--SIGNIFICANTLY DIFFERENT FROM THE LONTROL MEAN----WITH A VARIABLE-WISE FALSE POSITIVE (ALPHA) ERROR RATE OF 0.05. (4) WITHIN-GROUP M E A N S Q U A R E . + SIGNIFICANTLY DIFFERENT <P<0.05> FROM CONTROL GROUP BY LSD. * SIGNIFICANTLY DIFFERENT <P<0.05> FROM CONTROL GROUP BY DUNNETT TEST AND LSD. * SIGNIFICANT AT THE 0.05 PROBABILITY LEVEL. O # 015 IS* no1 ,0eS afflf APPENDIX i (cont'd) BODY_ WEIGHT SUMMARY H* 12037 GROUP INTERVALS IN TEST DAYS 15 16. 17. 18. CONTROLS LOW (.001 MG/L) INT (0.008 MG/L) HIGH (0.08MG/L) F RATIO(l) LSD(2) DUNNETT<3> W M S (4) 295.4211 294.5789 306.3684 283.1765+ 5.756* 10.9620 13.2205 280.0308 300.6316 301.0000 311.1053 287.7059+ 5.447* 11.3719 13.7149 301.3677 303.5789 305.6842 317.21056 294.8235 5.240* 11.2223 13.5345 293.4909 302.8947 305.8421 317.2632* 292.2353 6.347* 11.3577 13.4978 300.6151 311.7368 314.3158 326.1053* 304.7647 4.494* 11.7205 14.1352 320.1234 GROUP INTERVALS IN TEST DAYS 22. 23. 24. 25. 26. CONTROLS LOW (.001 MG/L) INT (0.008 MG/L) HIGH (0.08MG/L) # F R A T I O (1 LSD (2) D U N N E T T (3) W M S (4) 323.7368 327.8421 340.6842; 320.0000 329.4211 335.0526 346.5789* 326.8235 4.0?4*j 12.5176 : 15.0966 365.1474 : 3.609* 13.0048 15.6841 3941240 342.5789 345.6316 358.4737+ 341.8824 2.432 14.0325 16.9236 4f8.8793 348.0526 351.8947 365.2105+ 343.8824 2.459 14.4293 17.4021 485.1951 350.7368 355.9474 3is9 7368 351.233CJ 3,017* 14.4640 17.4440 487.5339 (1) RATIO OF AMONG- TO WITHIN-Gj?QUP VARIATION-- ONE-FACTOR A N A L Y S I S OF VARIANCE. , h P ST sisnif?CANT DIFFERENCE-GIVEN A SIGNIFICANT (ALPHA=0.05> F RATIQr ANY TWO MEANS DIFFERING BY MORE THAN THE LSD ARE SIGNIFICATLY DIFFERENT WITH A VARIABLE-WISE FALSE POSxiIVE (ALPHA) ERROR RATE OF 0.05. < TM NETT TEST-- ANY TREATMENT MEAN DIFFERING FROM THE CONTROL MEAN BY MORE I HL V ^ f Z L 5 I ^ TISTIC 15 SIGNIFICANTLY DIFFERENT FROM THE CONTROL MEAN WITH A VARIABLE-WISE FALSE POSITIVE (ALPHA) ERROR RATE OF 0.05. (4) WITHIN-GROUP MEAN SQUARE. . + SIGNIFICANTLY DIFFERENT (PC0.05) FROM CONTROL GROUP BY LSD. * SIGNIFICANTLY DIFFERENT (PC0.05) FROM CONTROL GROUP BY DUNNETT TEST AND LSD * SIGNIFICANT AT THE 0.05 PROBABILITY LEVEL. > - 16 - 016 ,, j . 0 0 00' Sant c o m P any \ APPENDIX 1 ( c o a t'd ) BODY_WEIGHT SUMMARY H# 12037 GROUP INTERVALS IN TEST DAYS 30. 33. 37. 40. CONTROLS LOW <.001 MG/L) INT <0,008 MG/L> HIGH <0.08 M 6 / L) F R A T I O <1) LSD<2> D U N N E T T (3) WMS<4> 375.0000 376.8571 373.9286 376,666/ 1.687 19.8178 23.9589 653.2662 388.5000 392.7857 410.3571+ 5Y3.166/ 1.750 21.1564 25.5772 744.4948 403.2143 401.9286 424.0000 407.6667 1.736 22.3711 27.0457 B32.4391 414.4286 416.1429 435.9286 420.4167 1.418 23.8561 28.U409 946.6198 <1> RATIO OF AMONG- TO WITHIN-GROUP VARIATION-- ONE-FACTOR ANALYSIS OF VARIANCE. <2) LEAST S IGNIFICANT PIFFERENCE**~GIVEN A SIGNIFICANT <ALPHA=0.05> F RATIO, ANY TWO MEANS DIFFERING BY MORE THAN THE LSD ARE SIGNIFICATLY D^FFEREN? W I T H A VARIABLE-WISE FAL S E POSITIVE <ALPHA) ERROR RATE OF O.OS. <3) DUNNETT T E S T -- ANY TREATMENT MEAN DIFFERING FROM THE C O N T R O L MEAN BY MORE TM E D UNN ETT STATISTIC IS SIGNIFICANTLY DIFFERENT FROM THE CONTROL MEAN WITH A VARIABLE-WISE FALSE POSITIVE <ALPHA> ERROR RATE OF 0,05. > WITHIN-GROUP MEAN SQUARE. SIGNIFICANTLY DIFFERENT <P<0,05) FROM CONTROL GROUP BY LSD. # SIGNIFICANTLY DIFFERENT <p<0.0$) FROM CONTROL GROUP BY DUNNETT TEST AND LSD. ) 17 - 017 Company Sanitized. Does nol contain TSC.&tCB! GROUP APPENDIX 1 (Cftt'J-- BODY WEIGHT SUMMARY J H* 12037 INTERVALS IN TEST DAYS 44 44. 51, 0 54. 5A. CONTROLS LOW <,001 MG/L> INT <0.008 MG/L) HIGH <0.08MG/L> F R A T I O < 1) LSD<2> DUNNETTO) WMS <4) 433c777B 438.8809 452.8889 423.1429 1.284 30.9153 37.8438 962,4064 440*2222 445.0000 459.4444 430.2857 1.250 30*0398 37.7513 957.7069 459.3333 463.8889 476.4444 450.2857 0.821 34.1047 41.7479 1171.2180 473.1111 471.7778 486.5556 460.2857 0.664 37.2445 45,5914 1396.8032 475.5000 468.7500 485.0000 481.0000 0.114 66.8715 83.8552 1704.1591 <1> RATIO OF AMONG- TO WITHIN-GROUP VARIATION--- ONE-FACTOR A N A L Y S I S OF VARIANCE. (2) LEAST SIGNIFICANT DIFFERENCE-- GIVEN A SIGNIFICANT <ALPHA=0.05> F RATIO. IFFERING BY ORE THAN THE LSD ARE SIGNIFICATLY DIFFERENT UITH A VARIABLE-WISE FALSE POSITIVE (ALPHA) ERROR RATE OF 0.05. L ,1e ! T~~A H Y t r e a t m e n t 'm e a n d i f f e r i n g Fr o m t h e c o n t r o l m e a n b y m o r e IHL,E T,.?ITI STC 13 SIGNIFICANTLY DIFFERENT FROM THE CONTROL MEAN WITH A VARIABLE-WISE FALSE POSITIVE (ALPHA) ERROR RATE OF 0.05. 4) WITHIN-GROUP M E A N SQUARE. o + SIGNIFICANTLY DIFFERENT <P<0.05> FROM CONTROL GROUP BY LSD. * SIGNIFICANTLY DIF F E R E N T <P<0.|05) FROM CONTROL GROUP BY D U N N E T T TEST AND LSD; Company Sanitized. Does not contain TSCA CBK a p p e n d i x 1 (cont'd) BODY WEIGHT SUMMARY H* 12037 GROUP INTERVALS IN TEST DAYS 61. 65. 68. CONTROLS LOW (.001 MG/L) INT (0.008 MG/L) HIGH (0.08MG/L) F RATIO(l) L S D (2) D U N N E T T (3) W M S (4) 483.2500 , 494.2500 476.2500 1 466.0000 493.0000 503.7500 491.6667 504.3333 0.133 67.8778 85.1171 1755.8333 0.174 70.2745 88.1225 1882.0152 503.0000 494.0000 512.0000 513.0000 0.148 72.5293 90.9500 2004.7273 i 72. 507.7500 500.2500 519.0000 526.6667 0.220 70.3120 95.6934 2219.2879 75. 514.5000 510.0000 529.5000 535.0000 0.209 80*0436 100.3727 2441.6364 GROUP INTERVALS IN TEST DAYS ??* : 82 86. GCONTROLS W (.001 MG/L) T (0.008 MG/L) U G H (0.08MG/L) F RATIO(l) L S D (2) D U N N E T T (3) W M S (4) 523.2500 517.2500 538.5000 543.0000 528.7500 523.5000 545.5000 554.0000 0.224 79.6470 99.8754 2417.5000 0.278 . 32.4204 : 103.3532 i 2588.7954 536.7500 528.2500 551.0000 558.3333 0.241 84.8947 105.4559 2746.5606 89. 543.2500 533.7500 557.0000 565.6667 0.231 90.1867 113.0919 3099.6516 93. 549,7500 541.2500 563.2500 576.3333 0.252 92.6716 116.2079 3272.8106 GROUP INTERVALS IN TEST DAYS 96. CONTROLS LOW (.001 MG/L) rNT (0.008 M G / L ) -IGH (0.08MG/L) F RATIO(l) L S D (2) D U N N E T T (3) W M S (4) 534.7500 541.0000 566.0000 578.6667 0.284 91.5977 114.8613 3197.4016 Company Sanftfzed. Does not contain TSCA C8I 2B a p p e n d i x 1 (cont'd) ( 1) RATIO OF AMONG- t o WITHIN-GROUP VARIATION-ONE-FACTOR ANALYSIS OF VARIANCE, w SSSS-- " THAN FR0M THE CONTROL HEAR BT NORE WITH A u A S r i S r I T. , f I i T I S T I C IS'SIGNIFICANTLY DIFFERENT FROM T H E - C ONTROL-MEAN WITH A VARIABLE-WISE FALSE POSITIVE (ALPHA) ERROR RATE OF 0.05. (4> WITHIN-GROUP MEAN SQUARE. + SIGNIFICANTLY DIFFERENT (P-C0.05) FROM CONTROL GROUP BY LSD. * SIGNIFICANTLY DIFFERENT CP<0.05) FROM CONTROL GROUP BY DUNNETT TEST AND LSD I o 020 20- TSCACompaiqr Sanitized. Doesnoicontain C^- APPENDIX 2 i 21 - 0 2 1 C0mpany SanBfeed. Does not contain TSCACB| 1 m GROUP final wgt CONTROLS LOW LEVEL(0.OOlMG/L) INT. LEVEL(0.008MG/L) 266.8000 284.0000+ 281.0000 HIGH LEVELC0.08MG/L) 262.8000 F RATIOC1) LSD(2) DUNNETT(3) WMS(4) 3.964* 15.6916 15.4673 136.9750 heart 9420 1.0000 -9700 .9000 1.404 .1076 1335 .0064 lungs 1.4340 1-6220 1.5680 1.6720+ 1.761 .2316 .2874 0298 livrr spusrn 10.5340 11.5680 15.9740# 16.4300# 14.4^4* 2.3757 2- 9473 3- 1397 5380 .6480 .6830 .4320 5.736* .1444 .17*1 .0116 GROUP KIDNEY TESTIS THYMUS CONTROLS LOW LEVELCO.OOlMG/L) INT. LEVEL(0.003MG/L) HIGH LEVELfO.08MG/L) 2.3020 2.4860 2.5840+ 2.4200 2.7580 3.0280+ 3.0140+ 3.0180+ .6140 .5540 6640 -4100# F RATIO(l) LSD(2) 0"NNETT(3) WMS(4) 1.648 .2765 .3430 .0425 2.932 -2277 .2825 .0288 10.293* .1027 .1275 .0059 # ^^ HatC-'oO of ajmDoOnQgg-- Cn C2) Least significant different Uf\ Variatlon ne-factor analysis of \ any two means differing by more than !* *ignifica (alpha-O^OS) p^ratio3006* ` * b l . + I . . false posit .. (.'iLf Jlffor.pt ` : . : : s = : s r r . , r cL t significantly differenc (p<0 significantly different 'p <0 051 f! co"trol group by LSD. fn d .LSD- " 5) fl0a COntrcl roup by Dunnett test Significant at the 0.05 probability level. itfai ' l Company Sanitized. Does notcontain TSCA CBI 022 - 22 - 1*1 *lC**T AiS)Uin H a ... >J 12037 A SACRtflCBD A r a ,, M T ,, u CROUP FINAL WCT CONTROLS LOW LEVEL(0.001MG/L) IWT LEVEL(0.008MG/L) HIGH LEVEL(0.08HG/L) F RATIO(I) LSD(2) DUNNETT(3) WMS(4) 337.6000 349.6000 362.2000 354.0000 1.400 25.9962 32.2516 375.9500 HEART 1.1820 l.2900 1.2940 1.1860 1.745 1416 1757 0112 LUNGS 1.8820 1.8320 2.0080 1.7560 1.360 .2722 .3377 .0412 LIVER li.2860 li.8880 16.9420# 18.3940# 7.343* 2.0922 2-5956 2.4351 SPLEEN .7280 .7900 .8580 .7100 1.839 .1483 .1840 .0122 GROUP CONTROLS LOW LEVEL(O.O01MG/L) INT LEVEL(0-908MG/L) HIGH LEVEL(0.08MG/L) F RATIO11) LSD(2) DUNNETT(3) WMS(4) KIDNEY 2.7860 2.8920 2-9800 2.9320 .825 .2725 .3331 .0413 TESTIS 3.0120 3.2100 3.0740 3.36204 1.934 .3252 .4159 .0625 THYMUS .8780 .7980 .9300 .7420 1-453 .2075 .2574 .0240 (-> Least signtficant d i f f e r e J e - J i v ^ Jinifi"" * T r a"aIy8* of P l a n c e , any tuo aeans differing by ore ^han th L 88nif^anfi:ialPha"0 -05) F ratio, with a variable-wise false positive falnhaf0 si nlf^Icantly different (3) Dunnett test-- Anv treai-!* C if*8* error rate of `5- than the Dunnetc statistic is significantly^?ff ^ with a variai ,-wise false positive f a S L ? ^ COntro1 ea" by .ore froa the .trol ean <*> .Within-group Mean S ^ L r l ^ ^ error raCe of -05- ^ icantly different (PfCk ha r * Significantly and LSD. different tterent ((PP<<00.*0055)1 I"" fro. Catro1 control grouP b7 LSD. group by Dennett test * Significant at the 0.05 probability level. .i Company Sanitized. Does not contain TSCA CB| 023 23 - 12037ijRjAOHT6SAHS/ABCJRDYTFICED A 2^ 5^ CROUP final wct SCONTROLS JJfcLiO.OOlMC/L) INT LEVEL(0.008MC/L) HIGH U W L ( 0 .oS ) 408.0000 400.6000 438.SOOO 441.4000 F RATIO(l) LSD(2) DUNNBTTO) WMS(4) 2.330 40.9799 SO.8407 934.2250 HEART 1.2620 1.3780 1.4600+ 1.4600+ 2.557 1756 .2179 .0172 LUNGS 1.9360 2.1260 1.9360 2.1580 1.367 .3068 .3806 .0524 LIVER IS.6660 15.8460 ^8.2420+ 19.0520# 4.940* 2.2972 2.8500 2.9357 spleen .7400 .8400 .9140+ .8680 1.907 .1598 .1983 .0142 CONTROLS LOW LEVEL(0.001MG/L) INT LEVELfO.008MG/L) HICH LEVEL(0.08MG/L) F RATIO(l) LSD(2) DUNNETT(3) WMS(4) KIDNEY 2.8640 3.0460 J.35B0# 3.4720# 6.384* .3319 4117 .0613 TESTIS 3.2320 3.5160 3.4420 3.3720 .949 .3721 4617 .0770 THYMUS .7040 .8220 .9100 .8140 1.087 2427 .3011 .0328 ,(1) atin of among- to within-group variation * " f"s differing by .ore chafth. ?sS i.'*11*" -0-0 F r*tlo. > r u t n (ai^ > with ath' r `" St*tl,tI'*i"e"^"If"cMtlfy rdIff,r' '!* by .or. /y y v^lable-wise false positive faloha( erent fr the control aean (4) Withln-8roup Mean Square! ( P } errr rate of 0-05. 9 Significant^ different ( P o ' 0 5 ! J" " COntroi 8ro"P by LSD. and LSD. 6rent (P'*5) fr controi group by Dunnett test Significant at the 0.05 probability level. Company Sanitized. Does notcontain TSCA CBf GROUP CONTROLS if? LEVEL(0.001MG/L) HIGHLEVELfC-08MG/L) LEVEL(0.08MG/L) 481.6000 483.8000 493.0000 453.0000 f RATIOC1) LSD(2) 00NNETT(3) WMS(4) .825 55.0991 68.5913 1466.5714 1.4720 1.4760 1.4750 1.4000 .407 .1709 2127 0141 GROUP CONTROLS LOW LEVELCO.OOIMG/L) INT LEVEL(0.008MG/L) HIGH LEVEL(0.08MC/L) F RATIO(l) LSD(2) DUNNETT(3) WMSC4) KIDNEY 3'-0880 3.4360 3.2075 3.2325 1.136 4353 .5419 .0915 TESTIS 3.4880 3.5620 2.8575 3.6625 1.555 .8484 1.0561 .3477 2.0560 2.1520 2.3625 2.0550 1.439 3537 4403 .0604 THYMUS .8740 .8280 .8450 -8375 .061 2558 .3184 0316 17.5420 17.3360 18.6273 17.2750 .453 2-7410 3.4122 3.6293 *8760 8840 .9675 .8000 1.064 1912 2380 0177 - - ~ s : . 1sz 5 s u t.,,# c- icantly Jifferent (P<o os^ r "tli Company Sanitized. Does notcontain TSCA CBI 025 GROUP FINAL WCT CONTROLS LOW LEVEL(O.O0lMC/L) INT LEVEL(C.008MC/L) HIGH LEVEL(0.08MG/L) 554.7500 541.0000 566.0000 578.6667 F RATIO(i) LS0(2) DUNNETT(3) WMS(4) .284 91.5977 114.8613 3197.4016 HEART 1.4850 1.6475 1.6675 1.6067 .863 .2852 .3576 .0310 GROUP CONTROLS LOW LEVEL(0.001MC/L) INT LEVEL(0.008MG/L) HIGH LEVELC0.03MG/L) F RATIO(l) LSD(2) DUNNETT(3) WMS(4) KIDNEY 3:3975 3.7675 3.9375 3.6967 1.462 .6042 .7576 .1391 TESTIS 3.4575 3.5950 3.8175 3.6000 .691 5797 .7270 .1231 LONGS 2.2150 2.1875 2.4175 2.2700 1.345 .2865 .3592 .0313 THYMUS .6425 .5925 .6625 .6533 .333 .1734 .2175 .0115 lives 18.3800 19.4525 20.4775 18.5267 .558 4.1112 5.1553 6-4411 SPLEEN .7775 .9325 1. 1100# .8633 4.975* .2035 .2552 .0158 > Of variance, vljh " *ria"Ied" ierSlae " S c i ' ^ a ^ " " * ^ " ` ` ^ K f e r e a T Cl0' (3) Dunnetc test-- Anv rr..; (alpha) error rate of 0.05. than the Dunnett s t a L L ^ control aean by more -ith a variable-wise false pos fve alo^I *U t m t fr" th. control L i n (4) Within-group Mean S q u a K ( ^ error raCe of *5* a!nd SLSSDf. i " S J diifrfreerreenntt ({P<0.X05) ffro^a cConnttrro0l1 gr"o"u*p b*y DLuSnD.nett test * Significant at the 0.05 probability level. Company Sanitized. Does not contain TSCA CBI 026 27 - Company Sanitized. Does not contain TSCA CBI 027 CROUP CONTROLS LOW LEVE1.(0 .OOlMC/L) INT. LEVEL(0.008MG/L) HIGH LEVEL(0.08MG/L) F RATIO(l) L50C2) DUNNETTf 3) VMS(4) HRGAN/BODY WEIGHT MEAD RELATIVE DATA H# 12037 RATS SACRIFICED AFTER 10 EXPOSURES HEART LUNGS LIVER SPLEEN .3534 .3519 .3441 .3424 .277 .0308 .0382 .0005 .5371 .5698 .5589 .6365# 2.920 .0752 .0933 .0031 3.9259 4.0695 5.6781# 6.2513# 24.180* .7078 .8781 .2787 .2032 .2269 .2454 .1644 4.059* .0520 .0645 .0015 GROUP TESTIS THYMUS CONTROLS LOW LEVELC0.001MC/L) INT. LEVEL(0.0Q8MG/L ) HIGH LEVELiO.OSMG/L) F RATIO(1) LSD(2) DUNNETT(3) WMS(4) 1.0356 .2300 1.0651 .195CH- 1 - 0 751 .2361 11482+ .1563# 2- 233 10.410* 0950 .0342 H-79 . .0424 0350 .3007 KIDNEY -8635 .8750 .9188 9211 1.132 0835 -1036 0039 a?y tuo arts differing by more than the iSn fre P f='05) F ratio- with a variable-wise false positive 'alnh^ significantly different (3) Dunnett test-Any t ! e a Z ean K r" e f *05* thin the Dunnett statistic is signif ic 1 f*^ ^ COntro1 nu`,,n bY ore witl> > variable-wise fals- poJzfve i dltferent ^ e control mean (4> /Wtthin-sroup Mean Square! '^ M t e f -05* I sii"i,H1Cant!y di" eren!: iP<*05> front control group by LSD. ,,andh ,LS?Dr".,flcantiy 3 irrerer.t (P<0.05) fro control ggrroouupp by Dunnett test * Significant it the 3.05 probability level. Sanitized. Does not contain TSCA CBl Company 028 23 '1&CAN/B0DY WEIGHT MEAN RELATIVE DATA 12037 RATS SACRIFICED AFTER 14 DAY OBSERVATION PERIOD GROUP HEART LUNGS LIVER SPLEEN KIDNEY CONTROLS LOW LEVEL(0.001MG/L) INT LEVEL(0.003MG/L) HIGH LEVEL(0.08MG/L) F RATIO(l) LSD(2) 0UNNETT(3) WMS(4) .3504 .3689 .3574 .3359 1.192 .0379 .0470 .0008 .5574 .5247 .5541 ."965 1.473 .0705 .0874 .0028 4.2285 4.2593 4.6752 5.2236# 5.105* .6170 .7655 -2118 .2155 .2266 .2374 .2000 1.385 .0407 .0505 .0009 .8241 .8278 .8237 8301 .019 .0671 .0833 .0025 GROUP CONTROLS LOW LEVEL(0.091MC/L) H1 ISGTH LEVEL(0. 008MC/L) L E V E L O .08MG/L) LFSRDA(2T) I0(1) WDMU5N(N4E) TT(3) TESTIS -...8998552920027162 1. 1. 05 45 15 .1291 .0060 THYMUS ..22 52 97 88 ..22150543 ..i00.656749436 .0016 (2) tll'sl signif icnt d'ifferea-e--e iven^3t ^?n~7p?e~^actor analysis of variance, v.j. . variable-wise faise ,,,,strive ;,lpto) ,, ,, r! .mC.-{O. `l , .l t'h?mf l-.ag .br.ol eu' pl' i Ms eeanf a-S-l sq-eu*a-rrpIeSo. ssi it igvneifi(Aca^alrtpnitihL'a. )y emdrirrfrofererreernnattt e tfrorofoam0 .ft0hh5pe. control mean ` an d CSSiL-i -SgsDnmi.tfiiccaa.nntt llyy iidfiffpfurerprenerfnl lt; f (Un/'<vn0_ .p- Jc5.) 051 ff-.rrTMoomm contro. control KtgrroouuDpP bb"yvy LDt 5cu>nDn*nett t e s t " 31nlfii-anc at the 0.05 probability level. Pompan? SanKcmL Does aaieaetat&TSG&cSi 029 29 m\ Si . " ^ ttUAW/ISUOY WEIGHT MEAN RELATIVE DATA f j H # 12037 RATS SACRIFICED AFTER 28 DAY OBSERVATION period GROUP CONTROLS LOW LEVEL(0.001MG/L) INT LEVEL(0.008MC/L) HIGH LEVEL(0.08MG/L) F RATIO(l) LSD(2) OUNNETT(3) WMS(4) HEART .3094 .3432+ .3338 .3311 2.060 .0298 .0370 .0005 LOtNGS .4739 .5323 .4439 .4886 2.576 .0687 .0853 .0026 LIVER 3.8374 3.9509 4.15b2 4.3190# 3.800* .3295 .4087 .0604 SPLEEN 1812 .2094 2073 .1969 1.769 -0291 .0361 .0005 KIDNEY .7023 .7618+ .7666+ .7873# 3.408* .0593 .0735 .0020 GROUP TESTIS THYMUS LOW LEVEL(0.00IMG/L) INT LEVEL(0.003MC/L) HIGH LEVEL(0.08MG/L) F RATIO(l) LSD(2) DUNNETT(3) WMS(4) .7949 .8799 .7873 .7646 2.540 .0950 .1178 .0050 .1724 .2061 .2055 .1840 .981 .0512 .0635 .0015 (2) L e i significantdifferenceUP}V3r^a t o n e - ^accor analysis of variance, anv -wo dyterence--given a significant (alpha-0.05) F ratio with^ varUbifi ^ , by are th3R the LSD 3re significantly different^ * (3) Dunnorr --wise false Positive (alpha) error rate of 0.05. than the D u n n e " * 1 x T i s ^ i differinS fron the control mean by more With a variahff ^ " C 15 significantly different from the control mean (A' \-irh-1 bl false Dosicive (alpha) error rate of 0.05. {*, Withm-group Mean Square. &*" Significantl,y d,iffereenn<t- fprn from controli group b.y LSD. .i LIS. * f - TM 1 group b, Duuu.tr tost * Significant at the 0.03 probability level. i Cort1Pany S a n ity 0oes^ c o ntafn 7sCA CBl 030 I r&ban/BWi wtioni n&AN RELATIVE DATA 12037 RATS SACRIFICED AFTER 42 DAY OBSERVATION PERIOD GROUP CONTROLS LOW LEVEL(0.001MG/L) INT LEVEL(0.008MG/L) HIGH LEVEL(0.08MC/L) F RATIO(l) LSD(2) DUN.NETT(3) WMS(4) HEART .3067 .3065 .2993 .3098 .112 .0383 .0476 .0007 LUNGS .4286 .4464 .4795 .4571 .620 .0817 .1017 .0032 LIVER 3.6410 3.5886 3.7843 3.7997 .688 .3839 .4779 .0712 SPLEEN .1825 .1829 .1959 .1753 .640 .0309 0385 .0003 KIDNEY .6442 .7144 .6512 .7127 1.447 .0974 .1213 .0046 GROUP CONTROLS LOW LEVEL(0.001MG/L) 1ST LEVEL(0.008MG/L) HIGH LEVEL(0.08HG/L) F RATIO(l) LSD(2) DUNNETT(3) WMS(i) TESTIS .7257 .7417 .5846 .8095 2.219 .1830 .2278 .0162 THYMUS .1811 -1719 .1710 .1848 .171 .0492 -0613 .0012 U ) Ratio of among- to within-group variation-- one-factor analysis of variance, (2) any Least significant two means differing difference-- gi by more than ven the a significant (alpha=0.05) F ratio, LSD are significantly different ' with a variable-wise false positive (alpha) error rate of 0.05. (3) Dunnett test-- Any treatment mean differing from the control mean by more than the Dunnett statistic is signifi cantly different from the control mean with a variable-wise false positive (alpha) error rate of 0.05. (4) Within-group Mean Square. + Significantly different (PC0.05) from control group by LSD. ? Significantly and LSD. different (P<0.05) from control group by Dunnett test Com 31 - 031 'Oes n o t c* / TM "'buui i B i w n r u n RELATIVE DATA H7 1203? RATS SACRIFICED AFTER e4 DAY OBSERVATION PERIOD GROUP CONTROLS LOW LEVEL(0.001MC/L) INT LEVEL(0.008MG/L) HIGH LEVEL(0.OSMG/L) F RATIO(l) LSD(2) DUNNETT(3) WHS(4) HEART .2668 .3046# .2946+ .2787 5.485* .0229 .0288 .0002 LUNGS .40i j .4054 .4276 .3965 .487 .0617 .0774 .0015 LIVER 3.3153 3.5910 3.5955 3.2076 3.609* .3160 .3963 .0331 SPLEEN .1399 .1723+ .1964# .1507 7.572* .0290 .0364 .0003 KIDNEY .6119 .6960# 6955# .6424 7.540* .0485 .0609 .0009 GROUP CONTROLS' LOW LEVEL(0.001MG/L) INT LEVEL(0.00SMG/L) HIGH LSVEL(Q.OSMG/L) F RATIO(l) LSD(2) DUNNETT(3) WMS(4) TESTIS .6215 .6640 .6779 .6269 1.276 .0774 .0970 -0023 THYMUS .1153 .1162 .1171 .1155 .085 .0327 .0411 .0004 ( ) Ratio or among to withm-group variation-- one-factor analysin of variance. C ) Least significant difference-- given a significant (alpha=0.05) F ratio any Lwo means differing by more than the LSD are significantly different ' wi i a variable-wise false positive (alpha) error rate of 0 .0 5 . ill iJnR^ tC teSt" Any tieatnent "eao differing from the control mean by more than -he Duanett statistic is significantly differentfrom the control mean -ith a variable-wise false positive(alpha) error rate of 0.05. (-*) Within-group Mean Square. T Significantly different (P<0.05) from control group by LSD Ind5ilD!fiCanCly different (P<0-05>^ o m control group by Dunnett test Significant at the 0.05 probability level. - 32 032 COfl|jPany sa, fo e s n o t e" * " T ScA 0% APPENDIX 4 a n a l y t i c a' l r e p o r t January 26, 1981 S. L. KENNEDY 2S D EVEL0Fm n: department (JOB- -------------- *1 BLOOD SAMPLES ^ S k M l J ^ i S r 02^ 376- 80-674S9-485' sam ples has a f ty t l on subacute te s t, a serler. o f ra t blood iionsfd igCcihaveteen1d0i7nt hs eaTmraebpllwee sa sI .r e c eAisv er edq u6fe/n8s0t e*,d,*w l th i f. d e n t^flL t group i Mo if 6ao^S ahsbaem^rsp l"e sS<t*(Lpctlusu>rsr`e bn Alta ns^kt tasl)t nu sg, a>n-a*ly sbeede.a dt rtih.ids ftoirm e. o ^ T h S e r 6J c So a dTi t i o'n s a s""t h e o t n e r s , b2ut -nPo ti - Ah se rwe e l ad isstc uysesaerd f ionr ^opuer cmi feiectindge ot ne r1^/3S/8l 1i ^ o t f -h f3 P8 e Cr ^t ^f.U m0Ja0t0 "S raaipl0h1i cc amceitdhoidn dbe lvoeolodp. e d oCfg cthr _'*. atyrapbel,e atos wtheolsle a so f n o n - s ^ e c -if icc ^ r rSa3n1i c ffl uSo r i n eS^d eUtledr mgiiVnSa tivoanlu f?os r f soara nCloeCsal w h ich iia s n o t p r e v i o u s l y b e e n a v a i l a b l e TM *"* D ^ d is t r i b u C i o a f Cg is o m e rs A. Com parison o f AnaTyCf caj. M e^dg f o r t o t a l o r g S ^ S ^ ' i s *8/C C T * 7 1 th e " ^ b o l d Torch a n aly sis P a r h e r s t r g T ^ t i f f* S awhleent tceorr r fercotme dn jfjo^rH rlHe cHo vg el-roy o f Cg. D etS L y l 2 r 3l ceoxmp epra:uraisecnoc aaI r su ndcies cr tuasisneidt y i n` Seven of th ese ra t blood sam ples were also n t- - " d 1,1 th e t i b l e - " T f C8 fay t h . tfic k b o ld T o rc h p r o c d u r o - 34 - o'"IIty 034 There's a world o f things we re doing something about e* Oo/ Co.-'ji . 5//J Q?/ m e S s ' f M t t r ' S T t t f "? b* %8 1 C B M vork Jmj ^ittoujl, based oo c h L Zttitti'?" U 0ver2 i taJZT?blank saaple (80-fi74HA> . d d,ta Che extent correct* by ! eas slsfactory 7 " * * - U b early CiS>e S b o u ld b**e Values* ^ c o r d i ^ 0f | j ^ 2 S d 4130 b*7 7 " * " cheBdatry 87, S45-Juyjf)fep0t" '1 *> " S ^ S S y ^ ' S " " 7 *' - ta l Coop eratio n nf ^ Pius four * Table 1 for overall c* H S P" liiC " ia;" " - ' ^ o ^ i l b " c 7 ? S S S (acrajghe~chad0 J found CO contain detectable tedchere none of the six cTMParison " " " to -- -- CS- " le * - * 5 ' % . - p J 2 * 2 . " 2 T 2 r j f * " ~ - . recovery tine In pt 7^ar t square lines have been Seu,iy'* c a l c u l a t i n g 1x1 Fi^ure 2. it is not clear rhae through the p n S ? ^ " ? Jlul"e1" . linear O " * 2/siope) ^ - o e se Le nf tlo 1b?e 6a b"o"ut *aU d aaycs) Fo? ^S i L'u**r 7g8r o u p s , h a l f ' -- rthUtl * TM -- rh, ,T r. 7 e e - ,, ' S Study.) -- as for ^ ^ j u s e d here was the same as_ ^ " W re sfiow" ia that usea in-your inhalation ^ . 4 i 2 5 * 5 s r s r . S i r - ~ * * . 2S5 S-a^:i: 'V p ^ e " issepsahroartnely, MbUbn^tbi'oii1" '" " f" "s r*a*lghhast-cnSoti, bce"eJn ^f Sf , "r tte th eT1-dividual beewxrxoaccuneelncdpth-tefbiodoewn.io*ss'*,o74mv*Tearl,sua-^ea-sdj . that fo rtfg ffift lfffo r l S*r "aacMetnrhtroerftie?cld*ef^!et^1eh ^e--ar^ree^,* *lao*veceBoe r-Wrre(ecssrpcTMaoar?nnn.d.lidinaga lrcvd"uaiiaxwu9ce4ev*df-Qf r s a c r l f k (S" ? " r " b u tf o ro*wNr a^mrena^mcahJ"'lfSseaCvnamnJda a fro. r d ' ^though never as low as -:5eLai r ^ j " : s ies a r a b l e contrition fro peak #i 035 - 35 - 'hyo ^ O,es OOf e3iJfe,7, rsc/ WlU1* n** f*r, cheonly isoaer ea a u , h . which appeMarrss to be] iR suggests tfhka.t. t L V H W n ar- ^ _ 4 tructure has been assigned is #5 ^ccooaappeerrllssoonn aof eGrC ii-ajd nmmh d^a^"ar).. ______9_ a S n.uorines--1 * position has been been d a t a n t a e ? Bjalong the chain, but Ac cachaencs fat Keywords: ^Bl o o d analysis P e rflu e ro e c e a n sa c e s. S. Stafford o 03K 36 - ^ If*l *ecf ^o/ C3ftf3 ; 9` t> /oe4 c*/ Sjtcrlfig 0 ns7s 2/29/80 Group 1 <co"Crol) II (1 ng/s3) I U (8 sg/ijj3j IV (80 ag/nt3) II JL Rat # 1 2 3 4 5' 270322 270323 270326 270327 270330 6 7 8 9. 10 11 12 13 14 15 270638 270639 270640 270641' 270642 270678 270679 270682 270683 270684 16 270720 17 270721 18 270724 19 1 270725 20 270728 PRAl No., Aa Heeelinj PRAt Ho., Drlad 80-60270 80-60271 80-60272 80-60273 80-60274 80-67459 80-67460 80-68604 80-68605 80-68606 80-60275 80-60276 80-60277 80^60278 80-60279 80-6 7461 80-67462 80-68607 80-68608 80-68609 80-60280 80-60281 80-60282 80-60283 80-60284 80-67463 80-67464 80-68610 80-68611 80-68612 . 80-60285 80-60286 80-60287 80-60288 80-60289 80-67465 80-67466 80-68613 80-68614 Statua fl>) A A A A A A A A A A A A A A A A A A A Days 3/14/80 n 1 2 3 4 5 6 7 8 9 10 270330 270332 270333 270334 270335 270643 270644 270645 270648 270549 80-60290 80-60291 80-60291 80-60293 80-60294 80-60295 80-60296 80-60297 SO-60298 80-60299 80-68615 80-67467 80-67468 80-67751 80-68616 80-68617 80-68618 80--68619 80-68620 80*^68621 _A L L A A A D S D D III 80-68522 11 12 13 14 15 270685 270666 270687 270668 270689 80-60300 80-60301 80-60302 80-60303 . 80-60304 80-68623 80-68624 80-68625 80-68626 D D D D D 20IV 80-68627 16 17 IS 19 270302 270730 270731 270732 270733 80-60305 80-60306 80-60307 80-60308 80-60309 80-6 7469 80-67470 80-67752 80-68628 80-68629 D A A A 037 Co< rs , Sacrlieft 3 28 Days 3/28/80 n hi IV 4 42 Days 4/11/80 II III IV TABLE I (coo't) Tube - Rat i PRALtto., A * Received PRAL Ho., Dried 21 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 1 2 `3 4 5 6 7 3 10 11 12 13 14 15 16 17 18 19 270336 270337 270356 270357 270358 80-60310 80-60311 80-60312 80-60313 80-60314 80-67471 S-67472 80-67753 80-68630 80-68631 270652 270653 270656 270657 270658 80-60315 80-60316 80-60317 80-60318 80-60319 80-67473 80-67474 80-67754 80-68632 80-68633 270690 270691 270692 270693 270694 80-60320 80-60321 80-60322 80-60323 80-60324 80-67*75 80-67476 80-67755 80-68634 80-68635 270734 270735 270738 270739 270744 80-60325 80-60326 80-60327 80-60328 80-60329 80-67477 80-67478 80-67756 80-68636 80-68637 270359 270384 270385 270414 270415 80-60330 80-60331 80-60332 80-60333 30-60334 80-67479 80-67480 80-68638 80-68639 '80--63640 270659 270662 270663 270668 270669 80-60335 80-60336 80-60337 80-60338 80-60339 80--68641 80-68642 80-68643 80-68644 80-68645 270695 270698 270699 270702 270703 270745 2/0296 270297 270310 80-60340 80-60341 80-60342 80-60343 80-60344 80-60345 30-60346 80-60347 80-60348 80-68646 80--68647 80--68648 80--68649 80-68650 80-67481 80-67482 80-68651 80--68652 Status(b) PL L A A A L L A A A L L A A A L L A / CL A A A A D D D D D N D D .V 0 ^ i _' U1 : ! 1 j 1 1 1 270444 270445 2704 74 270475 80-6034S 80-60350 80-60351 80-60352 80-68653 80--68654 80-67757 80-68655 A A A Ac 038 Company Sanitized. Does not contain TSCA CBi TABLE I (con'e) II i'll 17 "Test Blanks Normal control rats(c) PRAL No. A* Received PRAL No., Dried 5 6 7 8 270670 270671 270674 270675 80-60353 80-60354 80-60355 80-60356 80-68656 80-68657 80-68658 80-68659 9 10 11 12 270716 270717 270718 270719 80-60357 80-60358 80-60359 80-60360 80-68660 80-68661 80-68662 80-68663 270311 270312 270313 80-60361 80-60362 * 80-60363 80-67768 80-68664 80-68665 SUttt|(bj 0 0 0 0 0 D D D 278358 278357 278356 278355 278354 273353 278352 278351 278350 272994 80-60366 80-60367 80-60368 80-60369 80-60370 80-60371 80-60372 80-60373 80-60374 80-60375 8-0---6-0-3-76 80-67759 80--6 7484 80-67485 80-67483 80-68670 80-68671 80-68672 80-68673 a8O0-68674 D (7/80) 0 (8/80) 0 (7/80) O (8/80) A A Stored as deceived L A A A D each enclre^sainpla^as Portions to analyse. 7 phlI~2ed at the of analvsi ^ assigned a second S Nof ^ f o r ^ t l S ^ ' (b) Current Status: a Samples r, . S & ' S L * e " L* i f 1*! iost ^ I n g less of vacuumla the a n - t f analyzed for rePed here stora8e'buc aoc ^ d fotie roup of 13. due O Blanks Included with the Sanra7 group of samples samples submitted 6/80. One 9i ,,1. 3 " ts each (Table III) ^ ) Company Sanitized. Does not eontain TSCA CBI 039 ! ' jj Comparison of Cfl/CC and Wlekbold Torch An,l,,.e3 of Rac BlooH 0 P5AL No. 80-67461 80-67462 80-67752 80-67756 80-67481 80--67460 SO--67484 Sacrifice-Tube 1-6 1-7 2-18 3-18 4-16 1-2 Test blank SC Analysis, fCa ]. UtF/f; M^vl 7.7 13.1 11.4 8.6 1.3 1.1 <0.007 (nose detected above reagent background) Wickbold Torch Analysis. Total Fluoride, ug F/g blood gacorrected * 1/0.830) 6.9 8.3 10.5 12.7 9.5 ' 11.4 9.0 10.8 1.8 2.2 1.1 1.3 0.76 0.92 O (b) Recovery currently ,,. ,. ^ is Company Sanitized. Does nnmot tain TSCA CB^l - 40 - A3LE in (eon1e) a> f ^ y * 18 ,, r r r r r 21 (c ^ 7 ^ ah?TM the avcrag^0but ls ,n" " M " u * "te* ~ T g S * " * " ^ p S K ^ S S ^ F - 'j s ta , s s J> re used to calculate * " b2 5 r ta' " d ' I 042 - 42 Percent Scraight-Ch*.. tet Blood Sawpi^g (fl) "S " * " * - - P - in the w The satis calculation for s-nii-mj vi _ of 742 straight-chain forj^KB^^4Z of a ,, ^ ^ values T e ^ dfrofjis tThe-8^-r-e0-a'g1ents.? rS ? S ih e n^ a U ns S e r o f ch ! Sf empted fo r * P la s '* ^ f Cha seeondardy peaks and inter,feren i? i? * 043 - 43 - Wfee<' ^ Oof t$CA CBi Figure 1 - Comparison of Cg/CC and Hidebold Torch Analyses of Bat Blood Samples ' oData_from_Table XIS^using Jorcmh values ceowrirteecctseMd froorr 8833ZZ recovery Linear Least Squares Fit: Torch - 0.90 + 0.96 CGC) e Figure 2 - Concentration of Cg in Sac Blood Semples vs. Recovery Time Data from Table III, Average Values by GC - Group IV & - Group III 0 Group II X " Group I log C - 1.9 - 0.039 t (to 42 days only) log C 1.7 - 0.039 t log C - 1.1 - 0.038 t log C 0.078 - 0.038 t (to 42 days only, sample 3-20 excluded)
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