Document zm8VJxye13z98ZNpx21MEOG3

AttachmenPtesrftoluLoertotcetratnoe CS.ulAfouneartedaStteuddiMesay 4, 2000 AR 2o- 09h SEHR -0800- 373 apg pnd Acute Toxicity 1) APrnojAeccuttNeo.Inh7a8l-a7t1i8o5n,ToDxeiccietmybeSrtu3d1y, of T-2306 CoC 1979. (FC-95, PienrtfhleuoRraoto,cBtiaon/edSyunlafmoincast,e Inc., potassium salt) 2AFMcCau.ty9e53,1O,rIan1lt9eT7ro8nx.aiticoi(ntNayolt(ReL:eDs3Se0aM)rcfShitleausnddyiniDdniecvRaeattlesospwamimetpnhlteFsCloutroaprkoaerndadtuiFrolinun,ogrPotrchohejeesmctitucdNayol.wSeu1rr3fe7a-cn0to8at3n,t analyzed.) = 3) Eye and Skin Irritation Studies Report on Sample T-1166 (FC-98, Possum 2 thylcyclohexyl Sulfonate, presumed 100 %), Warf Institute Inc., Proje 2320 253 PNeo.rfl5u0o1r1o0e23, January 28, 1975. =2 4) Combined Eye and Skin Irritation Studies Report 1) Eye Iritation Study (with washout procedure) Report = 8S Ss RU) fal el Apich 5 an pale wih 7-297 Buowwek | Joe frp to = F-14337 Joined a 8 Fe 000813793R >S 3 EN o oF 001730 EiSETCod (G I R f0= Ca2c V=y ee Sip Fn 23 rs Division of Biology and Safety Evaluation PROJECT NO. 78-7185 AN ACUTE INHALATION TOXICITY STUDY OF T-2306 CoC IN THE RAT Submitted to: 3M Company Attention: Date: Dr. William C. McCormick December 31, 1979 001731 --_-- ee "mami ine 78-1185 I. GENERAL A series of one-hour inhalation exposures was performed on rats to determine the median lethal concentration (LCso) of T-2306 CoC dust. The test material, a fine white powder, received from the 3M Company was labeled "3M Company; T-2306 CoC". These studies were initiated on January 24, 1979 and completed on April 6, 1979. II. EXPERIMENTAL A. Test Material Delivery For each exposure, the test material was sieved through a 60- mesh sieve and packed into the large-diameter cylinder of a Wright dust-feed mechanism. Dry air, at flow rates ranging fron 12 to 16 liters per minute, was passed through the dust-feed mechanism. The resultant dust-laden airstream was directed into a 32.2-Titer glass exposure chamber housing the test animals. Desired concentrations were achieved by varying the air flow rates and the gear ratios on the dust feed mechanisms. The test material exposures lasted for one hour each. The packed cylinder, cutting blade, and nozzle were weighed before and after each exposure. The difference in weight represented the anount of material delivered during the exposure. The nominal concentration was determined by dividing the amount of material delivered by the total air flow through the chamber during the exposure. B. Test Animals The test animals used in this experinent consisted of groups of five male and five female Sprague-Dawley rats obtained from Charles River Breeding Laboratories, Wilmington, Massachusetts. Pre-exposure weights ranged from 201 to 299 grams. Observations for abnormal signs were recorded : 001732 -_-- P1%aynamics tne. 78-7185 II. EXPERIMENTAL (Cont.) B. Test Animals (cont.) prior to the exposure, at 15-minute intervals during the exposure, upon removal from the exposure chamber, hourly for four hours post-exposure, and daily thereafter for 14 days. Individual body weights were recorded prior to exposure (Day 0), and on Day 1, Day 2, Day 4, Day 7, and Day 14 (terminus). All animals dying spontaneously were necropsied as soon as possible after death. On Day 14, all survivors were sacrificed (ethyl ether) and gross necropsy examinations were performed. Blood samples were collected at terminus on all animals surviving through Day 14 of each group. The blood samples were drawn aortically, pooled by group and by sex and were sent to the sponsor for analysis. C. Control Animals In order to provide control data for this study, a group of five male and five female Sprague-Dawley rats, weighing from 203 to 263 grams were exposed to dry air at a flow rate of 12 liters per minute. All other exposure conditions, observation procedures, necropsy procedures, and blood sampling procedures were performed the same as for the test material exposed animals. 0. LCs0 Determination The median lethal concentration and 95% confidence limits were calculated according to the method of Litchfield and Wilcoxon.! Litchfield, J.T., and F. Wilcoxon J. Pharma. Exp. Therapy96: 99-115 (1949). } 01733 _-- ee PYanemiene, 78-7185 IIL. RESULTS AND DISCUSSION A. Exposure Concentrations During the test material exposures, totals of 44.13, 23.13, 6.77, 13.38, 2.06, 4.67, 0.0, 1.81 and 4.10 grams of the test material were delivered, yielding equivalent nominal exposure concentrations of 45.97, 24.0, 7.05, 13.9, 2.86, 6.49, 0.0, 1.89 and 4.88 milligrans per liter (Groups I-IX, respectively). A summary of exposure conditions and mortality results is given in Table 1. Results of the Group I exposure (45.97 milligrams per liter) were not easily comparable to the 18.6 milligrams per liter group of Bio/ dynamics project 78-7184. A second exposure (Group 11) was performed at approximately 20 milligrans per liter. Group I was terminated on Day 2 to allow for collection of blood samples from survivors (see C. High Level Exposures). Group IV (13.9 milligrans per liter) was also terminated (Day 1) as a result of a cylinder blowout during the exposure. Groups I and IV are not used in calculation of the LCsp value and Group IV results are not discussed in this report. B. Control Exposure No abnormalities were observed in the control animals (Group VII) during the sham exposure or upon removal from the exposure chamber. Dry rales was observed in one of ten animals at three hours post- exposure. The most significant observation recorded during the 14-day in- Tife period was dry rales (seven of ten rats) which was scattered in oc- currence. Exposure, post-exposure, and in-1ife physical observations are presented in Tables 7 and 15. Body weights, presented along with necropsy observations in Table 23, are considered normal. The most significant abnormal observation upon necropsy was lung discoloration. 01734 -- --_--_-- aveemicsine 78-7185 IIT. RESULTS AND DISCUSSION (Cont.) C. High Level Exposures During the Group 1 (45.97 milligrams per liter) exposure, a dense cloud of test material was visible in the exposure chamber making animal observation difficult. Labored breathing and/or gasping followed by closing of the eyes and reduction of activity were observed in all animals. Excessive salivation and lacrimation and mucoid nasal discharge were observed in some animals. Upon removal from the exposure chamber and during the four hour post-exposure period, red and mucoid nasal discharge, dry rales, and yellow-staining of the ano-genital fur were most frequently observed. These observations are presented in Table 2. By Day 2, three of five males and two of five females had died spontaneously. It was decided to terminate Group I on Day 2 in order to collect blood samples from the surviving animals. Samples are retained by the sponsor. Prior to their termination, survivors exhibited reduced activity, red nasal discharge, excessive lacrimation, yellow staining of the ano-genital fur and general poor condition. A full list of individual physical observations are given in Table 10. Body weights, presented along with necropsy observations in Table 18, were depressed in all animals prior to death. Abnormal necropsy observations were of lung discoloration and Tiver discoloration. In Group 11 (24.09 milligrans per liter), there was 100% mortality with the last spontaneous death occurring on Day 6. In-chamber observations were similar to those described for Group I. However, the onset was delayed. Post-exposure observations, also similar to those described for Group 1, were mainly of red nasal discharge, dry rales, and yellow staining of the ano-genital fur. These observations arepresented in os _-- se PYasnamiceine 78-7185 IIL. RESULTS AND DISCUSSION (Cont.) C. High Level Exposures (cont.) Table 3. Observations recorded during the in-life period, presented in Table 11, were mainly of yellow staining of the ano-genital fur, dried red material around the nose, and general poor condition. Weight Toss wes steady prior to the death of the animals. Individual body weights are presented along with necropsy observations in Table 19. Abnormal necropsy observations include Tung, liver, spleen, and kidney discoloration. D. LCs Exposures A series of five additional one-hour exposures were used along with the Group IT exposure in calculating the LCs value. In both Groups III and VI (7.05 and 6.49 milligrans per liter, respectively) there was 80% mortality. Observations recorded during each exposure period were similar to those described for the higher level exposure groups. Observations imediately following the exposures were also sinilar to those described for the higher level groups but were Tess severe. These observations are presented in Table 4 (Group IIT) and Table 6 (Group VI). In both Groups TIT and VI the last spontaneous deaths occurred on Day 10. Observations of yellow or orange staining of the ano-genital fur, dried red material on the face, and general poor condition were recorded during the in-1ife periods in both the survivors and those animals dying spontaneously. These observations were more frequent in Group IIT (7.05 mg/1), the higher level group. Other noteworthy observations recorded during this period were body tremors, convulsions, and breathing described as rapid, labored, or irregular. Other observations recorded during the 01736 III. RESULTS AND DISCUSSION (Cont.) Tees 0. LCso Exposures (cont.) in-Tife periods were scattered in occurrence. Individual physical observations are presented in Table 12 (Group 111) and Table 14 (Group VI). All animals dying spontaneously experienced weight losses prior to death. Those animals surviving the 14-day in-life period (62F and 63F Group 111, 120F and 122F - Group VI) had not regained their original Day 0 body weight by Day 14. Individual body weights and necropsy observations are presented in Table 20 (Group IIT) and Table 22 (Group VI). Abnormal necropsy observations for those animals dying spontaneously included Tung, Tiver, and small intestine discoloration and gaseous distention of the small intestines. Surviving animals sacrificed at terminus had lung discoloration (two of four rats) and absence of abdominal body fat (one of four rats). Groups IX, V, and VIII (4.88, 2.86, and 1.89 milligrams per Titer, respectively) had 20%, 10%, and 0% mortality, respectively. In- chamber observations were again similar to those described for the higher Tevel exposure groups but no mucoid nasal discharge was observed. Observa- tions recorded imediately following the exposures were most frequently of excessive salivation, micoid nasal discharge, and yellow staining of the ano-genital fur. Exposure and post-exposure observations are presented in Table 9 (Group IX), Table 5 (Group V), and Table 8 (Group VIII). Spontaneous deaths occurred on Days 7 and 10 in Group IX and on Day 12 in Group V. In-1ife observations common to these groups were mucoid nasal discharge, dry rales, and yellow staining of the ano-genital fur. Other noteworthy signs were soft stool, hypersensitivity to touch, 01737 -_-- ee UYanemiee 78-7185 III. RESULTS AND DISCUSSION (Cont.) D. LC50 Exposures (cont.) dried red material on the face, and rapid breathing. Abnormal in-life observations were less frequent in the Tower level exposure groups. Individual physical observations are presented in Table 17 (Group IX), Table 13 (Group V) and Table 16 (Group VIII). Animals dying spontaneously in Group 1X (170M, 180F) and Group V (103F) Tost weight steadily prior to death. Weight gain in the surviving animals was slower than is normally observed. In Group IX one of eight surviving rats did not regain its Day 0 body weight; in Group V four of nine and in Group VIII four of ten. When weight gain was observed in Groups IX and V it usually did not occur before Day 7. In Group VIII weight gain usually did not occur before Day 4. Individual body weights are presented along with necropsy observations in Table 25 (Group IX), Table 21 (Group V) and Table 24 (Group VIII). The most frequent abnormal necropsy observation was lung discoloration. E. LCs Determination According to the method of Litchfield and Wilcoxon, the estimated LCs value for a one-hour exposure to T-2306 CoC was determined to be 5.2 milligrams per liter with approximate 95% confidence limits of 4.4 milligrams per liter and 6.4 milligrams per liter. 01738 --_-- ee aveemic me 78-7185 IV. CONCLUSION A series of one-hour inhalation exposures to a dust of T-2306 CoC was performed on Sprague-Dawley rats. The nominal exposure concentrations of Groups II, III, V, VI, VII, VIII and IX were 24.09, 7.05, 2.86, 6.49, 0.0, 1.89 and 4.88 milligrams per liter, respectively. Total mortality was produced at the nominal exposure concentration of 24.09 milli- grams per liter. Partial mortality was produced at nominal exposure concentrations of 7.05 (80%), 6.49 (80%), 4.88 (20%) and 2.86 (10%) milligrans per Titer. Predominate physical abnormalities observed during the exposure and post-exposure periods were labored breathing, reduced activity, excessive salivation and lacrination, mucoid and red nasal discharge, yellow staining of the ano-genital fur, dried red material on the facial area, and general poor condition. The most frequent abnormal necropsy observations were of lung and liver discoloration. Lung discoloration was also observed in a high nunber of control rats and thus may not be treatment-related. The nominally determined median lethal concentration (LC50) for a one-hour exposure to T-2306 CoC was determined to be 5.2 milligrams per liter with approximate 95% confidence limits of 4.4 milligrams per liter and 6.4 milligrams per liter. 01'739 78-7185 oa Th . =) Directgr, Inhalation Technology (iWIdTE sE, 8RinJehaors,ssSeb Vice President, Science Report Preparation: Cecelia A. Bozak, B.A. Study Monitor 01740 10- 78-7185 An Acute InhaTlaabtlioen1Toxicity Study of T-2306 CoC in the Rat Sumnary of Exposure Conditions and Mortality Results Exwporsure Test Day of Last Group EDxaptoesed Ctornacteino-n DMaetleirviearled FlCohwamRbaetre ELexnpgotshureof Mortality_SpontDaenaethous mg/1 9 pm min. 11-2679 45.97 44.13 16 60 5/10 2 I 1-25-79 2.09 23.13 1 60 10/10 6 mo 31-79 7.05 6.77 1 6 8/10 10 wb 3.8.79 13.9 13.38 16 60 0/10 - Vo 3979 2.86 206 12 6 1710 12 VI 31279 6.49 4.67 12 6 8/10 10 VIE 3-13-79 0.0 0.0 2 60 0/0 - VII 3-22-79 1.89 1.81 16 6 0/10 - IK 32379 488 410 " 60 2/10 10 Group I terminated Day 2, not used in calculation of LCsp. CGornoturpolIV gtreorupm.inated Day 1, not used in calculation of LCsg. 01741 -1- An Acute Inhalation Toxicity Study of T-2306 CoC in the Rat Exposure and Post-Exposure Observations Key to Tables 2-9 78-7185 ey: NOA AG - NAonoO-bGseenritvaalble Abnormalities T - Removal from Chamber 01742 kn etTe tEonEio Ttorhey sity Crnsare aondwpostTEUagEmsSre Ogarattons ete prym, ee eee aHaGd -------- TT Zowhs cBeiSveI fSaMshE GteEreEs er[TTtaaiemsi rerweee oun sli olin ANS pose) p5raetor10 wore wer 5B&8 DBRooar lbBBbAuaRk m ww mmw=w Bor wer = wBBaeurlek lal =-- men = nas tep errn oy e eis or G0 ua " corn der dorm 2010 serio Sern 2eri0saw poe wBaw orm Toro sori [JSoaEemEoRzrEaaIRfI soerriiEEisEonn sam su TER Torn carTelrm 288 a83 Table 3 78.1185 An AcuotfeT-I2n3h0a6latCiooCniTnotxhiecitRyatStudy Exposure GarnoduPpos1t1-E=xp2o6s.u0r9epaO/b1servations TIintneersl WOM Brleabaotrheidng ELxaccersismuitvieon ESax1cievsastiivoen Cyloessed DisNcashaalrge RAecdtuicveidty RDarleys Moist I Yellow Nasal Riles A-G Furd Discharge eixnptoo"sure) P3r11estest 10 of 10 mst Toor 10 most a3sTo 1100 ooff 1100 dort PExopsotsure period 11800 T2oorfl1o0 2300 of 10 pfsote 10of 10 Tmsotr 10 10 of 10 mSoosmte 10 of 10 1010o0ff 1100 5. ? Toofor10 10 of 10 10 of 10 3010 30f10 Sof 10 Gloorrmi Tor 10 3o0fr100 30010 S1o 0105 0f orf1100 20f 1010of 10 B8oofr 1100 dor lo of 10 9of 10 3g 3>ES Table 4 78.7185 An feuotfe1-I2n3h0a6laCtoiConITnotxhiecitRyatStudy Exposure aGrnodupPos1t11-Ex-po7s.u05remO/blservations TIi--ntm_e--erval _WA2 Tinetoi. n, exposure) RAecdtuicveidty CElyoseesd LExaccersismiavteion SEaxlcievsastiivoen labored mNaswal Yellow Dry Nasal Breathing Discharge AG furd Rales Discharge Pr5etest 10 of 10 W0of 10 100f10 same some 05 WW00ooFF1100 1100o0f1100 Mmsotfo Tsotor lo msoosmte 10o0F10 100F10 100f10 10of10 sone 3.T i Wof10 100f10 W2o0r0l1d0 1S0o0ff1100 sone Ssoomfe 10 sort aor 10 PExopsotsure P12e0riod sof 10 1or10 100r10 20f 10 0S18o0 zSeormno Tof 10 5T0o7f1100 3d70000r01i1000 33To0ofrr11o00 1of 10 232 35a ~ es nones a etHe E B tc sot Cavan aHn oVt TgoeRs ration: --TM_-- sett tm Gots Gots Uboet han te po on mee fre RENR cg it Af Ye Sor rei3 t 0a 10 Bwairepan BwEaEr 8 Bul Buk Buk Bpuapk =m= r2on t a Basgaa u(nEg ER3E4 2 orto trio arn arn meBwroooauae wo tewh faToahnwl sEaR raaen iraalw tot zarn Varun ~ : 232 J33 wigwalt --- we EeeL aa TbR li SaN S Se S i ED mMEm. Ga Ba MIE . 23Rt 001 8i Wpy 23r0iiTtshme ah.gs#ome.. gBoowo. 2=go 3E2BBe rw [BEEREina RiE wWse 1u13gg p1HHEEg 1tue2nng atwowe wn Aw o-oo 2385 32 a7 Table 7 An Acuotfe1-I2n3h0a6latCioCon iTnoxtiheciRtaytStudy ExposureGraonudpPoVIsIt-E-xp0osmug/r1e O(bCsoenrtvraotlf)ons Tine TIntnerv.al _NOA2 into exposure) Pr1e5test 1100 ooff 1100 1350 11000off 1100 60210100off 1100 118200 1100 ooff 1100 234000 1090off1100 ory Rales 1of 10 78-7185 01748 T--i_n--e Intersal WoL Exnptoosure) P1re5test 10 of 10 5&30 roost" EPexrpioosdure 22W00B" s17o01r1l000 5 Gorlo RAecdtuicveidty 1o0f0f1100 1110000o0FFf111000 ClEoyessed Worl 111000000fFf111000 An Acute tohaTlaabtlieon8Toxicity of 12306 CoC in the Rat Study Exposure GarnodPuposVtIIEIxp=os1u.r8e9 eOab/s1ervations Excessive Excessive LiboredWNw asal Lacrimtion Salivation Breathing Discharge mTosotrlo 1M100o0offfl11o00 w1o0ofrl10 m1o10s0ot0ffl1o0 dorlo or 10 2o0rr 1100 mmsstt lo 1M01o0oorff 11l00o Bof10 20110 30010 3010 2of 10 nes A-YGellFouwra RabireyTs oHnu ateFrafcm ael 5. 9of10 lof 10 G1o 0 o2200f ff0111000 1or 10 zo lo 238 33T T--i_n--e Interval MOA Exnptoosure) Table 9 78-7185 An AcoufteT-I2n3h0a6laGtoitoniTnoxtihceitRyatStudy Exposure aGnrdouPpost1-XEx-po4s.u6r8emgO/b1servations. RAecdtuicveidty ClEoysesed LEaxccersismitvieon SDixiclevsastiivoen Blraebaotrheidng DmisMcashwaalrge AYeGllofwurd aOlreys Pre5test 10 of 10 Wor 10 most 10 0010 100610 same mmoosstt ossonte 3. EF3] WW0o0fF1100 110000071100 m1s0t0f10 omosstt mTs0otf 10 B &i 10 T000of 1100 110000ff 1100 mmosstt 0 mmsstt. sarin omsstt 3 of 4ofl0 eri PEpexorpsiotosdure 22100B" Ssooofrr1lo0o ddoorrl1o0 of10 2300fr1100 G30ofr1i0 2Tofof1100 1of 10 3 Gorm 20t 0 20f 10 2283 5aS -20- An Acute Inhalation Toxicity Study of T-2306 CoC in the Rat Physical Observations Key to Tables 10-17 78-7185 N.0.A. ~ No Observed Abnormalities. Agr. - Agressive Behavior he -)Act. - Increased Activity - Reduced Activity . Exc.lacr. Exc.Sal. - Excessive Lacrimation Excessive Salivation AG - Ano-Genital Poor Cond. - Poor condition 01751 To-7185. aNnoo sex wno on Bonon oN Fever Teste () DiHsacshaalrge ales At. Red Dry 1 21 i An Acute InhaTlaabtlieon10Toxicity Study of 1-2306 CoC In the Rat PhyGsriocuapl 1Ob-se4r5v.a9t7iomn/sl! iyHa-- tertaTlE -- perreatlon Dae LExicc.r. MAroosuend CEvleo(sse)d ASGtaiAnrses PCoonodr. SSotfotol 11 21 11 1 1 Wher Comulstons IBroedmyrs 1 1 MToosthaelr OofbseDravyesd 10. 2178 2 2a foFF ZF '1 1 1 1oa 12 11 12 i 3noroF 21 LE oa 22 1 22 TA total of 2 observations were reported during the study. Group was terminated on Day 2. Total mT mber of p abMgoirveean]ctbitcesriaatbisoenrvepdermsa.y"exTcoeteadl2nsuimnbceer oafn aanbismeaslatniaoynshasveaybeaelnsacbheselrevsesd wtihtahn 2mrdeuethoanthoenesapbonnotrasnaeloiutsydedautrhingofany 238 5a8 An deT te tice Teety sa Ptasateeovnsrctio]n] -- E aF-- O -- (0 -- oasiaJ e wiT e Ctree sM te 1RA 08etRoe el bneT lSaIteGHRbeRE eETR e pAor fc. NI oS n G Rrin e Tlet me [E@iR on 2 Lo Brood 1 } FE 1 1 Podi ' Vo. 3 ' P:iio oii vob ' ' va 233: i Ab oa[I rr ' ii1 ' vo ' :i votisoo i 3:ii ["ior sora 1 FEE vos ' vos V-- oram-- r eereo-- f e-- rtio-- nmy-- h cee--total -- mbaer-- orfdnr-- srhee-- ed -- (sall-- y 1, -- les-- theres-- ere spp-- oontane-- ous a-- th))s-- iean--fe--myh-- oveob-- 38 5a& ns ogaEfrEli)Fr Has Ta . ur ann. 2P 5 PrT err . OLE e SETHvI aIE. BD TE Seee giii}rii 1 ` vod;P]o Cs LR sPo ry. d, Ii} 2iFA 2E%i! , 1I , {1i 11 14 H:1ii N iI [oJ: E!R v: i];t 4i|: EEEeRe a arTeEer set ro re es, oe 08 23g5 3&d reef burne EE enonor, ET iatn.ploE ieriynymCoophle T BTNL.,w SNE Be rBOoSei ee BTeU SmD re HE mBiE oun '. mE 132 t vo Pp , +=}1 1 2 aa TT . "i Tr " By 23353a nes tnbesW te taR tionT Totty sty yHoss EonEiRon uA se wan,se ae. SEER SN ELS ER E, wR Po teTTT an, S41 g ont isml s tiesYe SSdGein WfWWiyhao o v\o i 'i ' wwnm ww ::iPoo PooP Pdta ld iiHiI y JiwBwrirl a wh . aria :1a2 \ mim"oowmm ommo o3 Yonifa nm i :Pa s : uoiR3 3 T eSeraST--S--EweTrd STRnmorboetryeeree Gye Wt ee ie amen) ie et or bn 382 aa : -26- 78-7185 An Acute InhaTlaabtlieon15Toxicity Study of T-2306 CoC in the Rat, PhGysriocuapl VIOTbse-rv0atmigo/n1s! TT C sat o ___Respiation -- atpeer_FgTpearaance T_ TypeOrthe-r _-- umTbotealr ANno.o Sex Non. HDisEcharIge Dr_yRTaloefsst "RAerdouBnrdoNwonse-- stoenTsoiutcihve oOfbseDravysed BBW wooKMo8W 3 2 wmoowwom 1 22 Woo 11 1 1 11" 11" 1" uw Fon LI uF 1 1u" WWw FFWou 3 1 1u uF 0 4 u TAabtnootramlaliotfie1s4 oobbsseerrvveadtiomnasy ewexrceeedrep14ortseidncedurainnganitmhael smtaudyy.havTeotbaelennoubmsbeerrveodf with than one abnormality during any given observation period. 01757 An Acute InhalTaabtlieon16Toxicity Study of 1-2306 CoC fn the Rat PGhryosuipcaVlIIIObs-er1v.a8t9iosngsl! E mr mR nie gr Tope Digs An6.. sex non, TDisechearrge ryRaHloestsT"BTraeapthlidng NVoMtaete eriaT lFouth TAoreaBrwow SStoofstt ESxact.. wwoow 9 mBOoK HoH 6 wwwmorooFF 8 FoFB4 3 2 2 ' [I ' a + 2 71 22 5 43s1 1s Toa roa1 1 1 7.7185 hevre vg Tuner SenTosuicthitveo OobfseDravysed 23 I"n} 2i inwo F4 2 " 54 I"r] 11 1I] 3 " TWoittahl monruesbtehranofonoebsearbvratoinosnsiatlymayduerxicngeedantootbaslervmautsiboenr opferidoady.s observed since an animal may have been observed 23RB 3a ns ReteBtE ntTotcey eos ScW r t OH ren! a8n se won, OMlieo MIpes _reNsningLRT T teens TeSUEBSoS arne caioe Ttart eseTosehrmuisttaiotes mooatrvSeeol w nhay: 3 wmaoyo : ' on oErYe 1 a Pro wBw weii.grt } ' wwn o Taster is d2 3 WE. i u@ 3i uiu 3i!i vkIi: : i VI ee oe of sE oretiI onsa ced toaSmTeArLofdLsSerLed alA y th, xcs nn nl ed s-onny) Shc 23 5a& es An AcTut2e 9In0b6aTlassCtotiteon1in8ToxtihecitRyatstudy Individunt BodyorHeeimghts aond Nwecroptsy Observations Eo se rrr re wow ome ow ue nTooww oBm omwe ww Woon ow ow ow wowomom om rr wr Necropsy Observations" 5.DurTTiuinnngggssammnodortttblrToeewddn.pdianrkk and dark red. red, pink, and Liver red. mttled 5.OanrlkuVnigspscuerrmpaolltetlSaenuddrfabpcirenokwnofanwdiLethdaTrobkbreoyFwedeareaLiv(1eronmotxtl1edcn) Cer i repos | en tater) an a) 8. Tungs mottled pink and white. sWa0Kreo.yuA:p,| -2SerNFmoiighnotabstseedrveo=dnTaOobafnytor2m.Bal2tbiielsa.teral. Spontaneous death, 38 3g S 5# nes An heuGtEeTTLIaZnb3hlDae5laGt1oi8otn(cfTnoonxttih)ceitRyatStudy Individual BodycVreoluopht1s-1a5nd.0Ne7crowpsayli" Observations E i w R oro e wT tecropsy Observations- n Z 5 r F0F oo@mm i1owmve wowe 555:.. TTTiiunnngggsss mmmooottttttllleeeddd wprheiidntkea,nanddordapanurgrpel,ree.da.nd Lpiinvke.r mttled surgle and brown. a Fm ww 07iLivrTeirngessomeraettndedd)oarkangorenedvaninsddcerrpeadulrwpilsteuhrwfiwathchieteobfrfoonct. w Foam ww 5,mievdTieuarlngsTTomtvoet,tlberdowpinIkn caonldaro.range. Entire surface of WKe0y.:A,R - rHioghotbsserve=dTaobfntorm8al beilsa.teral. Bsiapraonttpan1etoeursaidneaatthe:d on Day 2. 332 J2= &. nes An RuatfeTT2n3m0a6TaatsCitooetn1f9TnoutthecitRyatstudy Individual BodyGrHoeugpht1s1 a-nd24.N0e5cromp1sy Observations Nrsbeer ex ToyB VergeTosy OverNecrovpsy ati.ons ww ome om wm 5.dSaore1keurngvsehdartoantddtaertdkan.rdeadr.kUppreeSrdealaM]nIdSirneotdfe.stsipLnlieovsienrdiUmsGtihetEnldeerdded, now om om we 07wariiknnggbsirso.wrno,ttBeldackr,edanadndpduorrpklered.B. HLiidvneerysmomtottletdled 2 ow om wwe 52bSarunolgsnindotetspttuir1pneledes.ryoealSlpaolndewendaonrmdkotptrilkee..d fbnlLaiccvokelorra:nmdottpulrepdle. won om we 2 30 #2Jd"earTukinonrsoawnnd,otpipenukdr'ato1ernsacnogaleno,dr,rtaend., Small intestines and dork red. Liver DmGFortoB1Im6T4a"pvSuearaspt:lie,Siinsbicleeasrctakilsnesandudirfsatbcerenosdwendmoonwtiatthneteerst.ia"no,r Rrsoeusdr,fnaccaeensd wow ow wm ws wn 5.SpFurVgaihbnegd,eontmanonatdlt1befldaatcko;arraonwuganeidteanaddarreernaeadl.ong`1vLaiinsvdceserramaltntslKueirddfnaecbyersso.wo,f DSSFiIrTfb0a0ca8eto(faapamreodfxia.atl 3arToocbueandx(aad2prreconnxa),l, w132ihaicntndesa3raenoadF' ocdane).vrissco.esrael 3Brommrr- vorcamrveed srarm--tte--res--, ------------------r----------t--------. 38 osKpeoyn:iaRnco2ssrigdhetsanL = 1efts 8 + bilateral. & es An heuStHeT7TIa3nb0vl6aes1Ci9oodn(cfTnonottx.hi)eataytStudy Individual odyrWoewisght1s1 a=nd20N.e6c5romps1y hservations Noie se DyU TET ToDay? orgyiersTo] tecropsy Observations'z wf a0 we ue 5.T11RTuITngoosebaebtroiSgrhhtSihoreendedinnisaccoerlneodnrd:ownithdLoirvssecaralttaeo`rmseuordrfmatacalelns.yardea`arUskp: arom ws ow ve 5.fD"oirTronhegldes,borfighstplereend Hah red fn color. in cotor, ower MIF Liver mtled purple, rium: ana blacks bron and tan areas on visceral sur aFKioSdcanureseydso.fomedhidablaiannadt TaTfott aTrooeusnd(Sapiprroonsas p3adcmsxan1dGa). row ww 02aBrToosnrgesemroottmledanpdinbki,kr.ed, Saanrdeedarbkacrked.adLivperrvmiitled a roam we we 5.rT" eonttiuendgsiwnibtcrhoitgohartv.s.darTkWhaermTe,d.ofduLsoipdvleeenremn,abparenoadnraJslleyblfdaacrkk61Trnsed- w ora wows ee 5oCaottToiunin,eids b"aSlntatactnkls,eedhbrooorpwaannc:gtee,adnrdowdip,cuhraplnfedo.oddaSrkaarled:intLeisvteinres GSSCroierseemnnininbntodcyoTlotowracoahvnedridnigstesnddreednstWhhanodas. andAbskeinncaeseofan gd --- g2SovOe"rRMnOeEAs-sNrodioeabasenrved taabrntsorm8al+itbiielsa.teral. 4 Tres An AcBut1eTHT2o3n0a5TlasbCtloieton2f0nToxttheclRtaytstudy Individual RodyTreoiugphtTstan=d7.N0e5crmoapfs}y Observations Bw erm 0 wom om sow om ow 2 ow ow wm sox om wm wow ows om er wn am ow an uw mn ow om am Necropsy Observations 5.inds1nutnigasinsmotdStailaneldguo{srn.atnegsetinaensd yreadl.lowL-igvreerenmiintlceodlorpuropnlde T8.BhoytmluhisngssduarmrfkoatcetrsleeddofdThLa.rckolToaartn.edraMlAo.nTtolbuenrgesda.for1Laiinvgveree-rrmeomdtottlttelnde.dcolor TSdaeirmkisntacdoonfgaenusditedtda,.n. Thoracic cavity contains small 5. Tungs mottled red and dork red.T"ingisvmeroocodmersetdela.nd white. FspKoAanyt:Aaneo+2ustFoidgcehatbtsehr:ie=dsTohft:or=ebsil,ateral. 222 3J 5 8 w wes otS e TSotTeAe TcoEneD) y sy Ini toya Yt nd eros Oration @Nunber Serx. ofem RwYT mDey? DWayd DWay T ar mom ww we ay. 5a [aleEe TAoHeIENeA ScorouapnmshyeObnsemdravara tkfoTnn sEw*waoie etwen pti atlpgtictyd ui fblrTerl I h Be CaeE n etha OSa FLroBmBOoBmROEmEoRmORoOMw EYEom MEgnEoLsmemmrpteiit.e ye pe ST R LTT * N.0.A. - No observedabnormal fe, ities. 23&3 k. 1185 An AcuofteT-I2n3h0a6TlaabtClioeoCn2i1TnoxtihceitRyatStudy Individual BodyorMoeulgphtVs-a2n.d0N5ecmro1psy Observations Eo er he r yr mr NecropsyObservattons* S SM W a0s % Mz 2mm4 8 2220 18 o1w 18s 2235 21 M222B.8Blluluugngsss hhhaavveaerppevuidfrroecppfifo.llocciee.. 3B% AWZms m20w a2w8 219% AWoz 2202 ReHodOffAloecfutsoTonng.diapshurfracaeogfaL.posterior lobe WWo FFAzz WF we l1s lr w Bs w12 Ws io 2U8s 18 221 A ROOAA KOA WWF Z0 2 dk 12 Te Aof aL. TtaunngdemmoitdrtdlleediTtoabnoeoanfrdRp.urpTluen;g apnodsatenritorerantdhaoplrotst- C.a" vTaunTgobberigofhtR.redTunign aconldorp.osteLrifvoerr (hacsaudbarlo)wnhaalrfeaof A(ibseoncxe o+f5 caab)domoinnavliscboordayl fasturcfoavceerionfgmeaddiraennallsobe3.nd WF a3 WE 13 18 190 2 MKOidAneys. *as0Spoa.yn0?ta.nReo-2usWroigdhcetbasstehLrve=d Taafbtr;ana =tibielsa.teral. 238 . 28 7-185 An AcuotFeT-T2n3h0a6TlaabtCliooeCn2i2TnoxthieciRtaytStudy Individual BodyTrHoeulpghVtis =and6.N4e9crmo3/p1sy Observations Number Sex. TBT e rT TT Necropsy thservations mow me zs 2 5.dSaurrlkfuancrgeesdomfoatntRd.lebdrTooowbsre;an(ga11epgphroton.xd.bdro-or2wkcaarerdex.as-5Loincnv)ev.riscmeStrmtaallleld ginatestsinees nyelloofw-sgrmeean lin cfco.lorcoavnedrindgistKiednndeeydswistnhd mow om ow we um 52SdrTeinnagls Sgoltantdlse.d dark ind dundenim yellow inandcol1oHrg.ht Lr.ed.latJereajlunuTmo,befloefvs, mmooowK Be awss lwwm wemm L5.TivieTerirnmgmsootttpltoeltdetdedddaarrkrkedr,reeddtaanon,ndda1tniadgnh.tpingkreewni.th numerous red Rfaolcif.ofLisvteormamchitctreeadn bcorloowreda.nd tAabns.enceAntoferiaobrdominal moon om mae 8.vbeoddTyinagnfsadt.mdoatrtklebdroowr.angeSeanld riendt.estLiinveserymeoltltolge-dgredeanrk domicnaallorbaonddy dfiast.tended with gas. Avsence of abe eee eee --eeeeeerennet o *SpNKo.en0yt.:aAn,Reo-=usHroidgoehatbtsshe.Lrve=dleafbtr;ormBal=tbiielsa.teral. 8 $ aJ nes An AcuatfeTTLTaEab3bl0ae0taC2o2iton(fcTnoonxttih)aettRyatstudy Individual BodyYaVefroheson aand5Necrmoopsy Observations Number Sex rr TaE y7EeBay T r aT r Tay Necropsy Observations* Wo Fae woof wm mW ow we U6 ow WD wm UZ b5.laoi1nggss mottled pink and red. bright red in color. Avsence of shina Liver has alternating wer wo wwe we we an aCsoaltvcehsrensgSofseilrbeerrboauwlhiannakdnddmaKreikdlnreeiyds., Avene of fat woof ozs www 5:daarikcnoglrsoerd.satndAebsbderonwcdnea,rkofSreesndhid]agnadiInnaotireasnbtgoiedn.yes{oLytiesvletrovm-ortetelned wor om ow wm 5."ndindgosrksuvtetdledAorvaenngcee aofndsTheadossina"lLivbeortymotattl:ed brown a*sNKp.eo0yn.:tAa.Rnso-2ssNFoidgohetbnssne.rLveedTaafbtn;ormBal=itbiielsa.teral. 832 5 338 & 8185 An AcuotFe12t2a3h0a5TaatGbioloten2I3TnoxtihecitRyatStudy Individual GfordoytpHWoIiTgit=s0amndT"ec(rcoopnstyrolS)hservations | CAR E 2 E i aTa Necrmopsoy Orbsemrvaotionns' B MBo OWWNeEme mOmeEe E2g2eB 2#B96 E2z7m 73k 0DB.m lluogss mhuavtelemdipleilnkglreonydfoacrdhessn. ek rodtar green WWOoNw aOW oOEm Ze amWams 32 0srheilausmnessonptLii.nkewTdointg,hreddarakndrweaditfeo.ck. W WWeOF OFFo Ba3se m MBms 2EBe e2E8s A2a0e Z220O.aa lliuumgmsse mmpriittnlieewddithpriendfkaarankmddrepidintkfeowc.ii.th red foci. wWooOrF RwsOMa0 R 2 ezy Mms0 2ow9n d61.ivaKisdneymthiseddilpaintkedapnedivriosk. - - -- KKeOylA.& -= HroigohtbyseLrve=dalbefrtosra8al=tbeisla,teral. 23 B2gs : nes An Acuotfe2I2o3h0a5TlaatsCiototen2i8TnoxtihceitRyatstudy Individual BodSyeHoewlhVtisian1d1Ne8crompasty Observations EE rr er EE oro WBBpOoonMMB2sBMMmoo mgdEe0 2MHeo0 am2m00 N5dizB.wD.ollkournegss have rmerous red and white foci. mottled pink ond tan with ny dak foci. 5 We NW ow ze me ue we mz 0 a0 m9 1 Fb 3 5T6.ouTlvuhggistemmofitotctltleeddartpLai-nnkatnaodnbed:pignrkey.with memrous red fact; W Wo F zBies 8I Mda6e W1S9 21809 2210 55..TunllgiunngghssasmmotittntlleeTddorsppeiinnWkkhiaanntdde roferoadcnsig.ep.osterior lobe of A W W WF F F aBa0bORm8Er 1M11009 UW16sS9 1m16es 2Z1a9 505... lTTuuonnngasss mhmoactvttelleemddmrppoiionukksoannwddhitoLeroannfswoeic.it.h small dark fost. " KWe0yu!h,R -2 tioghcbtseUrve=daTbenftosrm8al= tbiielsa.teral. 382 33 3## nes an utT e ohE alTabaiotn2en5Ttoxhiecity Study Inivicun) BodycVetha1hs%eands8H8ecmsraopsy Gbservations Number Sex. wo ow TFTTBay7 am ms ws Day % me T Bay7 r Tag Necropsy Observations" 5.inTabngrsonb. riredgfncholatr, Livermattedpursle m mvVeoOow ooNnu aEEs OBEzp Em MEmREe MlOIs0SHwB)mD BNR GBmeo Bl5as En lluunngas:ppihontkthiweEidtThapaIkarwdokiatdfheebrcdehtia,oWrekerrkevditshetemrmieondrsague.sdreodct.oct. wor ow wm ws wun 5.oennTervunigomsroetroainsatuersfp(ta0ics5neeksltatonokenddehrredetadsso.nnd)LIiLn.ovcneotrlovohberena.rts.rabanldKrdsnuirsofteraecnerweds.esd W B Woo fL aR Bm MBSase 96 Me 1M ds WwW me 2mR se bblinTdslEiINnRgut npemierktRlaeswdeinphcie endkoafrakaanadrbdetddoanmmniia nitwaeilttwihfitanhtd.farpekawdk se.eddffoecci,t. J J [EI SOe :HAJ l vi 4 i a RA b"epK0aapnikane-o2usFNoadnebasttehr:ved1a8b1o8r5a8s +eblieast.eral. Sy weigh not recorded. | B33 5