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AR226-2787 FOR DU POMT USE ONLY Haskell E. I. du Pont de Nemours and Co., Inc. Laboratory]for Toxicology and Industrial ElKton Road, P. 0. Box 50, Newark, Delaware 19714 Medicine SUBCHRQINNHIAJL:ATION tQXICITY OFJ ofyB^in SUGARY; GcQUDs^ur 10 male pr1:CI- rats were exposed to either 0.31, 1.4, or 3.0 mg/L air. Exposures were 6 hours/day, 5 days/week for 2 weeks. A control group was Simultaneously exposed to air. At the end of the exposure ported and after a [13-day recovery period, blood and urine samples were collected for clinical {analysis and rats irfgre sacrificed for pathologi cal examination. No jvert clinical signjs control rats and rats exposed ^ U l f or, ain differences were noted between Clinical pathology measurements made at the end of the exposure and recovery periods showed no compound-related differences between control rats and rats exposed to 0.31 mg/L. Rats exposed to 1.4 and 3.0 mg/L had significantly Increased serudi cholesterol concentrations after the exposure period but not after 13 daysj recovery. Other differences were Interpreted to be within the range of biological variation. Gross pathological examination following the exposure and recovery periods revealed no compound related changes In any rats. Histologlcal changes were observed after he exposure oerlod In the livers of rats exposed to 1.4 and 3.0 mg/L. These hanges consisted of an Increase In hepatocellutar mitosis and hepatocellul br hypertrophy In the centrilobular area. Thirteen days later, no i mpound retated differences were observed. A comparison of organ and body weights between test and control rats showed no compound-related differences between control rats and rats exposed to 0.31 mg/L. Rats exposed to 1.4 and 3.0 ag/l had significantly Increased liver weights and liver/body weight ratios after the exposure period. There were no significant differenjces In mean organ weights and organ/body weight ratios aftir 13 days recover|y. _sed on parameters evaluated in this study, a no-effect level for ras established at 0.31 mg/L. Company Sani.t.i.z,e,.d,. DDoo.s^ir>n^o^0"^"1^0^ I- mINaTlReODraUtCsTIOofN' ; repTeheatepdurspuobseleothfatl heisxpostsuudrye wt61 concentrations were bajsedon the results of rmlne the affect on Exposure igel inding study where a 4-huur approximate lethal concentration was found to be 16 mg/L. II. PROCEDURES: A. Animals: Male, 7-Week old Crl:CD* rats were received from Charles River Breeding Labjoratorles, Kingston, New York. Rats were housed In pairs In 8" x 8" x 14" stainless steel, wire-mesh cages. Each rat was assigned a; unique Identification number which was recorded on a card affixed to his cage. Purlna Certified Rodent Chow* #5002 and water were avalllable ad jibitunj. Rats were weighed and observed for general suitiBTnity for approximately 1 week prior to testing, j B. Test Material; Purity: Contaminants: Synonyms: Other Codes: CAS Registry No.: Submitted by: Chemicals and Pigments Department Jackson Laboratory ofyygfj C. Exposure Protocol;j Groups of 10 rats, (weighing 216-243 grams) were exposed wholeymd^fl design concentrations of either 0.30, 1.5 or 3.0 mg/L A control group (male rats weighing 221-234 grims) was'exposed simultaneously to air only. Exposure was 6 hours/day, 5 days/week for 2 weeks. Rats were weighed and observed dally (weekends excluded) through the exposure period and for 13 days post exposure. 1:ion: Gaseous atmospheres were generated by syringe-driving jnfo the surjface of an Instatheriir flask. Flasks used for ?!eTow and the 1n|termedUtelevels were unheated; that used for the high level was; heated to 30*0* Dilution air was passed through the flasks to carrjy the gaseous tast material from the flasks to the chambers* _ E. analytical; Samples of chamber atmosphere were collected at 30minute Intervals by a gas-tight syringe. Samples were analyzed using a Hewlett-Packard 5790 gas chromatograph equipped with a flame ionlzatlon detector* Samples were chromatographed Isothennany at 1S5C on a 6' x 2 mm 1.0. glass column packed with 80/100 mesh Poropaikt}. Concentrations were determined by -c6S ;noic,o-n.^Wm" TS0" 2- ..Sa^-00' Gon^ comparison with a standard curve* Standards were prepared by quantitative dilution of the test material In calibrated ga$ bottles. Chamber oxygen levels were monitored w1;h a B1oniar1ne Model 225 Oxygen Analyzer. Humidity Was measured with a hygrometer, and temperature ' ' thermometer F. C''nical Measbi nen^s; Overnight (16 hour) urine specimens were cu 11ected from eachrat 3 days prior to the first exposure, after the 9th exposure, ailid after the 12th recovery day. Analysis Included quantitative measures of volume, osmolaltty and pH, and semi quantitative te$ts for occult blood, sugar, protein, bllirubin, urobilinogen, and k^tones. The appearance (color and transparency) was recorded and the sediment from each specimen was microscopically examined. Blood samples were taken from the tails of all rats 3 days prior to exposure and after the lOtfi exposure, and from 5 rats per group after a 13-day recovery period. Blood analysts Included measurement of erythrocyte, platelet and leukocyte counts; relative numbers of neutropMis, lympbocytes, ejaSinophlls, monocytes and basophlls; hemoglobin concentration; and mean corpuscular volume. Absolute numbers of'various types of leiikocytes were calculated from the relative leukocyte data. H^afpcrit, mean corpuscular hemoglobin, and mean corpuscular hemoglobin concentrations were calculated form the:erythrocyf1c data. The serum activities of a1ka1ine^hosphatas6, alanine ami not ransferase, aspartate ami notransferase and concentrations of urea nitrogen, creatlnlne, total protein and cholesterol were also measured. G. Pathology: Five rats from each group were sacrificed after the TOth exposure, and remaining rats after 13 days recovery, for gross and histopathologlcal examination. Organs and tissues examined were the adrenal and thyroid glands, esophagus, stomach, duodenum, pancreas, jejunum, Heum, cecum, colon, heart, liver, nasal cavities, spleen, sternebrae with bone marrow, mediastlnal lymph nodes, eyes, brain* trachea, lungs, kidneys, testes and epididymldes. H. Organ and Bogy Height Analysis: At each sacrifice, mean organ weights and organ to body weight ratios were determined for the heart, liver, lungsi kidneys, spleen, testes, and thymus (Appendices I and H), III. RESULTS: Chamber temperature ranged from 27<-34'C and chamber oxygen TeveTwas maintained at 211. Relative humidity ranged from 45-59t. ,^----TSWCBl - 3 - sanW20' Som,,P,, ^----' A. Exposure Data: EXP. r 1 2 3 4 5 6 7 8 9 10 LON (De^ani - 0.30 mmgg/L/L)l)| Mean S>..oD. iMngp' Intermediate (Deessiiggnn L& fgflfll//ii.).) Mean 5. P. Range 0.45 0.22 .001-0.7? 1.4 0.21 0.86-1.6 0.29 0.065 0.20-0.39 1.2 0.25 0.65-1.6 0.28 0.043 0.26-0.41 1.4 0.18 0.88-1.6 0.29 0.050 0.23-0.3^ 1.5 0.30 0.052 0.26-0.4^ 1.5 0.34 0.059 0.26-0.4^ 1.7 0.28 0.037 0.23-0.3^ 1.3 0.30 0.029 0.26-0.3^ 1.4 0.30 0.023 0.24-0.3^ 1.5 0.30 0.032 0.23-0.3^ 1.4 0.11 1.4 -1.7 0.17 1.1 -1.6 0.21 1.5 -2.1 0.18 1.6 -1.6 0.050 1.3 -1.5 0.057 1.4 -1.6 0.058 1.3 -1.5 Ove.'- i all* 0.31 0.097 .001-0.7^ 1.4 0.21 0.85-2.1 High (Deessiiggnn 3.0 mg/L} Mean s.D. Range 2.7 0.24 2.2-3.0 3.4 0.13 3.2-3.6 3.0 0.41 1.8-3.3 3.0 0.35 2.3-3.3 3.1 0.31 2.7-3.5 3.5 0.40 3.0-4.2 2.7 0.34 1.3-3.2 2.8 0.66 2.6-3.2 3.0 0.27 2.4-3.4 3.0 0.11 2.8-3.1 3.0 0.44 1.8-4.2 * Mean and Standard Deviation of Individual samples from all exposures. Wly^^ B^ Clinical Observations: Clinical observations of rats exposed to I Indistinguishable from those of controls. A few rats - from each group exhibited slight sporadic weight loss. Statistical comparisons of body weights showed no significant differences at any time throughout the study (see attached Growth Curve). C. Clinical Pho1ofly Statistical analysis of the clinical chemical and hematolug1cal <ata Indicate that rats exposed to 1.4 and 3.0 mg/L had s1gn1f1cart1y Increased serum cholesterol concentrations and decreased serun creatlnlne concentrations and platelet counts. These two groups ejicreted more uroblH'rtogen In the urine. Rats exposed to 3.0 mg/1 also had decreases In serum urea nitrogen, increases in serunr total protein, and excreted more alkaline urine. Following a 13-day recovery period, rats exposed to 1.4 and 3.0 mg/L had decreased hemoglobin concentrations. Rats exposed to 1.4 mg/L had increased serum aspartate aminotransferase activities. Rats exposed to 3.3 mg/L had decreased absolute numbers of monocytes. , ^olc^SCA.* ---Co^6""^ The dose-related Increases In serum cholesterol are Interpreted to be treatment related* The other changes are within the range of expected biological variation. The 0.31 mg/L concentration ofJUvJwas Interpreted to be a no-effect dose for the hepstologic and clinical chemical parameters measured under the conditions of this study. D. PatholOfly; No Compound-related effects were detected at necropsy. Histologicany, compound-related changes were round after the exposure -peri Qdijit the 1tecs- of rats -exposfid to 1^4- and -3.0 mg/L. Specifically, there was an Increase In hepatocellular mitosis, together with hepatocellular hypertrophy In the centrnobular area. Recovery was complete for both groups by the 13th day of recovery. ody Weight Analysts: Mean body weights of rats exposed re simitar to those of controls throughout the study. After 10 exposures, rats exposed to 0.31 mg/L had significantly Increased thymus weights and thymus/body weight ratios. These changes are considered Incidental because they are absent In higher dose groups* Rats exposed to 1.4 and 3.0 mg/L had significantly Increased liver we'tgtjtts and liver/body weight ratios. There were no statistically significant differences In organ weights between test rats and controls after 13 days of recovery. ^\ IV. CONCLUSIOH^^^ifidon parameters evaluated In this study, a no-effect TeveTToFaBByas established at 0.31 mg/L. Liver effects were observed at 1.4 and 3.0 mg/L. 1 Matarese, Catherine C. and Raymond M. Everett, "Clinical Patholgy Report No. 13 83," MR-4588-001, H-14.78?', August 12, 1983. 2 Stula. Edwin F. and William C. Krauss, "Pathology Report No. 38-83," MR-4588. H-14,787, June 2. 1983. ...C^ ^ ' . san11- ,,..^"t'inTS C^ 5 - Work anjd Report by; ""py.^th^omta's.J^A^. :K^e^ge^lm.an Technician Dale T. Turner Dale T. Turner Technician Simpevrised by: ^ ^ ^ ^ ' ^yi'.^^y ^ ..^.r /URayTaofntxtnlieecaoLlao. ngFilesetren^-r^1 Stuidy Director: v-\ [Approved by: TAK/DTT;sg1;3.18 Date Issued: June 27, 1984 Initiated/Completed; 3/7/83*3/31/83 Haskell Lab. Report No. 234-8)4 Number of pages In this report: 13 j^JU.>< Fald L. ^^JL\ Kennedy, i<Jr. Section Supervisor Acute Investigations TSCACB< ^contain Company 5Saa:"n1^" d.^3S - 6- == :2=o =gm Oo 5 =|--- | - { \ TN A ARNNAN Wa ) \ \ WN 85 5 ! ls : ~ i 3io o 2 A FON & | \, " " | NN\RQ ||| N\ \ | SD ! ND\ 8= F= a A: i l8o i |! ggg ggg gd 8 Is (SAVHD)) LHOIEM AG0dO oo" jo Le 6ROUP' CONTROL 0.3 M6/L t.^ MG/L 3.0 MG/L F RAT10<U L8D<2) DUMNCTTO) UMS(4) BRdUP ^ONTROl- ).3 MG/L L,!5 MQ/L !,0 M6/L F RATIO<1) LSIt(2^ aUMHETTO) MMS(4) (11 ' RATIO OF AMONG- TO W?'| ;2) LEAS I SI&NIP-tG^T fftF^ !NY TyO rtEAN8 DIFf^ERING ff'i KTH A Fnl.^E POSITI^K (Al-^ ;;> rHA^ i(ITH BHBw^fT resT-t^Y yRfc THHEt;Atf.iU;lAWBMLEET-Tt>lSi:f^fEtTISFTMSi,t.^, J| : 4 > UI.TKIN-6J5&UP ifltAN r SIGNIFICAHTLY Il^FFERE^'^^^Ji^T'.tfl^l SIGNIFICANTLY DIFFERENT ^N9.^ ^S^ --------------------------------------... A lil [flH-1^87 ^^BODY WEIGHT (WAHfl^ ^MMARY - Ol>9^VATrON PERIOD -'Strife GROUP CONTROL 0.3 MG/L .5 MO/L 3.0 MO/L F RATIOd) LSD(2) DUNNETT(3) UMS(4) INTERVALS W.;^^^^|i'Y8 15. ''' ! 9 " ...lSi ?, 17. 315.400^ 321.0000 Sl7.6S^K 308.4600 0.441; 24<043i 29.^293 321.6000 ^JA .3'i4,'^^jl)<l!^;^ aizA.^Bci^* -W^^ Nl?.;^^; "' .0000 ny 't'9'0 .8000 .4000 .6000 ,,IW^: ,ap-8^^. ; . '''^ --'y-Si3-^,"'' ^ ?'3~;' 1.082 .0261 ' '.^.^l^ii. S667 31-7. ^SiOa.: i-1-'! ^^S'' .9500 18* 320,6000 329.8690 330*8000 313.8000 1*199 22.0857 27.4600 271.3500 S 1 ' '| : '\ . ,. 'ifc' ^ 334.fljjB|. :.,-:^ 33A^%g^ ;^ . 322..2^|il?--';| 2 2^i ^^i. . ' 1 ,'| 292.^|,;.^| GROUP ;ONTROL >.3 MG/L 1*5 M6/L (.0 MG/L F RATIO(l) LSD(2) DUNNETTO) UHS(4) 1) RATIO OF AMONG- ]Ewrp;^L@ lili^'^s 22^, .r.^g||||^|% 24. 2S T"'"'"^^^!!"'^!!"""""""""""^"""""'"""'"""''"'' 354. eNfcNi. 3^9. 8^^;'' - 35&*.264" 348.8QOO ' '.' . . .:,?i^|tli^;^|?.0000 . 4000 -^m^^;*^^e|i|^M/;,^; tt.4000 .^.2000 .',-;:.:'''.,., "- ^^'"^\ -'^.f'''v^- -,^-i 358*4000 385 4000 3*3.0000 359*4000 0.85^', 29.125^'"' 36.133^ 471.906ir'. :;^,'^.^^?it|f;.^^1.0&7 r^*'^@ii,,|.'.i ^B.9489 '^3^.^^i;i^.:-.^.9147 a^.5^^^:.^ii|.2000 1.A23 29.9379 . 37.1417 498,6001 TO UI r^I.N-6ROUF .Nll^il^^-^E-FACTOR ANALYSIS OF Vftft2^ia^^ 2) LEAST SIGNIFICANT DSFF6^|E"-JBl?M NY TWO MEANS DIFFERING B^f '\W^^WSiWiP' ITH A FALSE POSITIVE (ALtH*) feRflja|gj|^ ;AMT (ALPHA'0.OS) F RATIO. JIGNIFICANTLY DIFFE^ENt 3) DUNNETT TEST--ANY tft^^M^-Wt,^ HAN ITH ATHVE ADRUI.NANBELT6T-WSfST'EA'T-lISl'TAI.LCMMII'p'sNNPIHW^y"M5"l' ^iRi^ DM THE CONTROL MEAN BY ENT FROM THE CONWOt HE( ^ - RATE OF 0OS ;;; ;^ ' ^ ' ^ 4) UIT.HIN-GROUP MEAN SQUARE. . '. ..,';' ^ .'.^ SIGNIFICANTLY LIFFERENT <P<Q-.05-) FR^.I|^|^iL^OUP BY LSD. SIGNIFICANTLY DIFFERENT (P<0.05) FRtIM C(M<TitOl.^ROUP BY DUNNETT TEST AMtl L8|, SanH^d-Does ^ Company. contain TSCACSl  m TOU,l OR f O . A N ^ y i O I L I r ^ * U E : TOU ;47a T 9 S < - ORAt( AT 'm ' ^ T; ^NllE OLU XPO TE SU R DA ES T A GROUP CONTROL 0.3 M6/L 1.5 MB/L 3.0 M6/L TEST - HOMOGENEITY TEST - TREND FINAl-^ T*. ^ "^.'^Fit^^ RT : ' ": " '"'i-"<'- '<' "n'l^y' pNi^ t - - - ^ ^ - 304:0< 30^s< <^ 305 .<6<" % .^^ism 30l.4;( .-:.:Hi . . . .. .^ :'^., fl1^^ ^-:- .^.-' '.: ST:..' fe ^ ,',^n^ 0. ';' - ?-<;; :^ ',, "^MfSSSiS^i^ ' ^^^I^^Sf- -, -- ; r.-ti.-'-i. -'t-y :' : .'.^ :jf^W;|gj -':7^"- -;^.l:s;^;^?;:^l^';^ 0. 00) 0. 61) 0. 79) 0. 97) GROUP CONTROL 0.3 MG/L 1.5 MG/L 3.0 MG/L TEST - HOMOGENEITY TEST - TREND ' ^'- .-r. ^"'-' { EN L^ ^;^,: "'".^"^^l --------'-^-'-s- ----3..--jc.iai.-. .-. .i^:'".;..!,.y,.<;M,YiS; ''' " ; ^ ll.44i(: " '' ^''^i-' .WS^, ;;;;.-,.^.:'^'JsI-^^s?^^I^I^''"^^^^ .;':'^:'^^^ite5s; .iis^e.^N^^ ^^Wf"^ .o^X: ...'.^a^^^^ :^ 14.. ^2|,-:' 'i^^Sfnf :.6t.)'T ;"'..i,:^%Iil . .-'; '' if^1- {sS# l^^l^ r ' ^ ^ i i i a i ^ i; ",i. -;,, ;,- ;'.. '.. .,;, -".-^-i.'^.''-'-'"';'-".'r?.-^;?'^ . 0. 00) 0. 53) 0. 24) 0. 72) . ^'. .L-o^^-Sr^^::;'^-i-Ni., ..^WiSK'te. GROUP LUNGS ;;' , ^ '.'S ^i >i; 1 52< 1 .53( 1 <SO( 1 38( 0*00) O.^O) 0.883 0.^9> ::;''"'i ^s ' I'1 . 0.21 0.09 KIDNEY ^ 's "- .^ . 1 -S 'I ) . 2 .59< 2 .64( 2 .59( 2 .74< -ft -oa.,.<7.^^^. ^iy^'ll e.9s -^ :'. : ' -' ' " " . .--1 -.'."^^"l ' ^'.^isIJ ' ../i-fi'5 0.86 '?' 0.52 .-^..^ :' .;.-" .'f^^ '.:' '' :',''''--^ ^ iS ^ " ^^ CONTROL 0,3 MG/L 1.5 M6/L 3.0 MG/L TEST - HOMOGENEITY TEST - TREND 2.72;< '^^^ffS^. 2.7^ . ,:^,^^ 22.,-7S9N<--:'^.^^^iS^S^^. ^^^^W'.S^ ^iN^^^ :^I^Si '''"''y^ ^SSss 0.00) o.oo). 0.13) 0.15-) '"''' "'i^&KhSis sssssasaaasssasaassaas.si^sB-giSs^^i^i^^As^a^l Values in parentheses^'^- .'P^^t<iiEi?6fe-':^l^"""""' fsss'sasasx'sasssissssxss's'vi^sW'ecss }:ST COMPAR;I80N INTROL MEAN. HOMOGENEITY - P VALUE ":||^||^g MEANS ARE EQUAL. TREND - P VALUE OF F TfeiS^ioilill^i^ TiieiilB^SE-RELATED CHANGE IN GROU^II^I^ '""'" -----<s"l:"-;- ^conta^ ^S^^'0.. noesf.0' GROUP I i BODY UEIOHT <ORAMS> - MEAN ABSOLUTE DATA IH-14787 ^ - 8A(?R^Cj|y^^^ ' " ,1 . i~'y' '-' 'ffCt'i OBSERVATION LUNOS CONTROL 0.3 MO/L 1.5 HO/L 3.0 MO/L 3S9.4( 385.4( 363.0( 359.4< TEST - HOMOGENEITY TEST - TREND 'i^Wi . '-^s^ ..N%;?POOOO) 0.121) ..,, :-.^1K8^0.91S) -;..:^t.l^^|0.775) 1707< 1.734< 1.774< 1.668K 0,000) 07A> 04<S 0.6A3) 0.667 0*777 GROUP Fsi_^^^.',^_;.i<^;-?tiy.anE"-:aii..-B. KIDNEY CONTROL 0.3 MG/L 1.5 MO/L 3.0 M6/L ^^eON^NiMM .""'iQs^^So'OOO) l5.23a 1S.164(:' :"(^.:S^|^^. i|^^%y^;,^o^^|((^). 9 1 7 IS^ZWBW^^il^ i ?' ' "''71"'. ..{y^' ;'/?'^^?? 'rr''1?*?";-^''^:-'''''^'?^'1 TEST - HOMOB6NEITY TEST - TRFND 2.992( 3,t7A.( 3l2A< 3.12;OS: 0.000) ^w ^491) ^.S>^B^-; 9*796 0.586 GROUP CONTROL 0.3 MO/L 1.5 MB/L 3.0 MG/L 2.696< 3.000( 3.0AO< 2.91&< TEST - HOMOGENEITY .^ ^^^glai^S TSTlL|S^;^:- ie -" - : .1" --., Tdi-e'r-T.ltf-"" ' -:''^-:-.- ."i;"'-*"-"'-1'-!1'?-1'*')'^';'ir^--^'"^; ' ; '-'' '"^'''SsSSa'iuSii ^---E-?-?^--^^------------ ' --' :....^jfct'A; ^^18) a;,. ,,/"0^6t|jl||).000) "-''^I-".---^ =35?' i.-^---"' - ';. . Lv ---- _ 9 - 71 KS^ "': ''^.|6)- _ 8 _ 9 ) 0,0.^5^::^"'.Ns|E!^|^^.22fl) 6^||):i^.. ,,^9||;^1|>.083) ;i;:^''"^^ TEST - TREND i3asxaxasaaa*fBaxcrKaa Value* in parnthv - ^|i|l^^^ HOHOOENEITY - P TREND - P VALUE ^(Hl VALUE OF .F "fetl; OF F .''s'.-"'"'".1;.'-'^: TEST ol".. lIHllrHE^ CHANGE IN GROUP HEAN8. II e3x*eaaaa*rii T COMPARISON TROL MEAN. x;rtili*- MEANS ARE EQUAL. E-RELATED ^ A 00'.s1 ^^e'-a-'^" se^ cav ^SC^ 00^" l^^^TM^ DRGflN & BdPY VET IHTfi (GRAMS) - RgglSTIVE DATA li------------IH14* 787 - AFTER TEN EXPOSURES - '. WV:.M GROUP . . -A .iwJ!!. .. -'.ftK ' -4^'; rf1-';*^ . LIVER CONTROl 0.3 MG/L 1.5 MG/L 3.0 MG/L TEST - HOMOGENEITY TEST - TREND GROUP CONTROL 0.3 MG/L 1.5 MG/L 3.0 MG/L tEST - HOMOGENEITY Ife ^1- 0.34't".^ :l3 0.35< : a 0.35't^ ^ 0.35^- - ' ' ^"N," p:.^-:; . ., '""^'^ ' :'-;rUJ&' '^gS ^ ^ 0. 00) .^i W 0. 75) . "'O^Wh.^. 0. 7S) ;0. 0. 06) ^ ^ ''";;'' '^^ 1 , '^lftj .--'!,-;;''J,-^." \, -- .:;^. ^^? ^C^fQ '" ^^i" l ' ,'1 ^'^ ^\ :"-!'' .'?= s-% '' ^ / - - '< ';. ''' .. . I./! Ms 'SB '^is^t^ ;..",*.- '''a -^"~;----"f-f -,. -.i ;;;'is ,: .-''^tyv-,' ';;tS; gs1" Y ^.^----------------.-,. '. *;'-? 3 .76< 4 .11( 4 .52< 4 .65( 00ft) ^fl7? 0<001 0<00)8 0.00 0*00 ^f TESTIS 0.2^ .-'^i ^^^^.'^iiiip^: o.,ii6!(. ";:;^.j^^ OV20<" ;,;;i;^ii^:::.'. l^.BpF;^^ 0.00 > ^^il0.68) 0.27) _.^:j^lijeifeiy "- -'-.' '^^"t;-!^'^,!''^^^'!^?;^' 0.9Q< 0.9|k 0.9K 0.85( -''dli's^.^^W^^- . --v'4^:^: -...^'sri;"--^. "-'-' TEST - TREND ,^o|pgl^'^^ ^ CONTROL 0.3 MG/L 1.5 MG/L 3.0 MG/L TEST - MOMOGENEITy ''TSli^^ - -,-. -v-f!-^js.-.^..: ..':' ', ^'^ ;'^i^', b^r-.^.iy 0.20 < '^ollp^:,: O.W ^1^1^: O.^^^' ^i,l2;|)^;;. tEST - TREND :sss=ss=='sa;=;s==s==acsi=cas;B'i-'-;s<E^ t^slues in parentheses - ,^|te HQMQBENErTY - P VALUE i s . T^.;.'";^i^-s^- t'i-^ ii=si*^a.a3&! .j .f*4^l SST :=SSS===E3i COHPARISGN NTROL MEAN. MEANS ARE EOUAL. TREND - ''^^^^/mis?^'- .. .,. . P VALUE OF F TES-T^^lliE^ir ^S||S-^S^ISE-RELATED CHANGE IN GROU^^Nil^^^ i;j?e^ ai^'^^ :'.^; ;% (.alVasZ^ . 12 ^C^^^ (mii)&H-B1O4D7Y87VE=IOHATGHI(FGIROAENSSL)oF- EHEARN Y3R-EDLAYATIOVBESEDRAVTAATION 3 I ] CONTROL 3 13hm 0.330 0/000) 0,W75( 0.000) 4.1140 0.0000 "3 CoElE RhEEb)o olSMEiE CSARSD MTEn e0nme 1 TEST - HOMOGENEITY 0.944 3 Jo fos 0.395 : TEST - TREND J-- [FER srueien TN | eRTM 0.280 % vests 24 ed at 5 oe conrroL 10..33 HHOo/sL 0.191 0.000) o01n19c30 2 88 OBC 0.000 i;a9:s825e01s1 00..589124)) o.rsac o.0gp) | | o0..7o855( oa is iti @ HF olisse Vina ove oid oud TEST - womooewEXTY 0.98.0 Ulais oz Fo a Test - TEND [i= Ni 3 # || oes T4 il=t arour Tivos .] a C01O.0N35TRwhOooLrstL 300 men oo0.,m2118c08(( s04l0e0n0y)" odasar it E5a4 ola ohh Go CL ; TEST - HONOGENEITY 0.29%, ag sig ad SEES 1. ai TEST - TREND 0.088 [KC id S Vetoa es innm arnenntr hesena - AUNCHE RGhAsISFSNHaEs aU Ea{SagB,eanrE nCsounRnvtana tTsonnmn n me aem fiyi oe HOKDUENCIT - UNLUE OF E4T BFWHETHER RDI news an coun. E TROND - CHAvNaGLEu.gIONFGROUTPEWBEGREKrEUMEVH1 ER THERG E 4Bpoe-neuaTen er 5 qatar1 -n- gam=e