Document 5k8YLqR2avpQndDyD61Doez1z

RISTOPATHOLOGY (Subacute Oral) GENERAL DESCRIPTION OF TEST Six male rats were given ten successive daily intubated oral doses of 2000 mg/kg of a 20% suspension of lead titanate catalyst in peanut oil. Tissues from three of the rats were collected at the end of the twelve day test period. Tissues from the other three rats were collected after a fourteen day recovery period. An equal number of male rats served as controls for each of the experi mental procedures. SUMMARY OF RESULTS 1. All rats survived the trials. 2. There was a significant decrease in the amount of perinuclear frothy hepatocellular vacuolation and in the amount of globular hepatocellular vacuolation in the livers of test rats. This was most marked in the livers of the three rats of the test phase. In addition, there was a decrease in the actual weights of livers of test animals (Table II) and relative weights of livers of test animals (Table III). This likewise was most marked in the three rats of the test phase and was consistent with the decrease in hepatocellular vacuolation. The livers of recovery phase rats occupied an intermediate position between test phase rats and control rats as regards both the histologic findings and weights. 3. A severe bilateral exudative pleuritis was present in R 56825, Particles of the experimental substance were evident in the pleural exudate. In addition, there was a large hematoma In one lung, peritonitis of the splenic omentum and degeneration of spermatic tubules with giant cell formation. 4. Manifestations of intercurrent disease-processes were observed in specimens from both test and control animals. No significant differences could be discerned between test and control groups as regards intercurrent lesions. . /;2 7 DUP040000955 H 3.437 page 2 DISCUSSION A detailed summary of the histologic observations are presented in Table I. The lesions of murine pneumonitis, hydronephrosis, focal nephritis, and hepatic microgranulomata were interpreted as the result of intercurrent disease processes. In R 56825, the pulmonary hematoma and pleuritis were interpreted as the result of trauma during intubation. The esophagus was probably ruptured and the material, in part, deposited in the thoracic cavity. The peritonitis was interpreted as an extension (direct or hematogenous) of the pleural inflammation. The testicular degeneration was interpreted as being related to the general de bilitated state of the animal which in turn was the result of both the experimental procedure and the experimental accident. Liver: The histologic changes observed in the livers of test animals were consistent with marasmus. This is substantiated by both the marked losses in total body weight and organ weight. The lesions were in the process of being reversed during the recovery phase. The changes seen in the livers were an effect of the experimental procedures which for one reason or another caused a conditioned malnutrition, i.e. interference With intake, absorption, assimulation, etc. Other Organs: No lesions were observed in the other organs examined (and listed in Table I) that could be attributed to the experimental procedures. CONCLUSIONS: 1. The experimental procedures produced histologic changes in the livers of test animals which Were consistent with marasmus, 2. The hepatic changes were largely reversed during the recovery phase and appeared to be completely reversible. Veterinary Pathologist o!r, t DUP040000956 /r f // ^ ^ >5 ^^SC\ ^S*i <SaSR(j) s<c Nt^s^ i\i fe >5. _\>j .^26^.. ^^ ^ >J >4 ' I 1 i1 1 r' ' ; f ( hi hi >. > \ v. i l V1 ^^^^l S ^^2\ o. *C<*3!i ** "1 Xi oo o ^ Fv N ^s hi <3 i C> i 1 1 (j> 1 'S i t i< ii : $ i i '-. i t-t- -~ i i^ ii i 5S 5'0 N35 Tv i\j h> "-JS5*^Ls. 2'?sh^ '<-n ' ^ Ij S v. 11 1 i1 1 ' iJ hi N > 1 * >* Vi ^>4 in- -v iff -*4 -^4> fs ^ ^ C3l ^ ^ <* ^ T ^ -~C+yl - V$ >5>5 >5 Tesi {PurM'en --clays ') O Q o RccovirY {"PurtMirn-- Jays) X>t> Manure a-f PeaJh hi hi -s. 1' t I1 1 ( ~v _ / / R M)torme, M>eurri0ru4-is ^ M/cart 4-is M& ata- M rxas MfJr*r>e pyrosis ^ fatalMef>h nr/'s ^ hi fo hs Ai >o Xi !1 i rf ........................<<-. /rof/iy yacuoleAion Cojebtilcif Aacuf'/a'fit'rl ^ Jf/c.("e>aMnw Ic mc J'& Mem&S/R r/r) A? Ox F 3 J MX AA MR MR MR fell i hi f MR MR MR MR.... | fe i /V-A MM MR MR MR %1 MX. MR MR MR MR | it SftRR/M /krMonth's BRA JM STAAIAaM.......... TMARST/MR Paa/c r ma s r//YMM<o -r MR. MR >* i i si^ MR. `i i ^ y. ^ ^v\ 1 "S. 1 MR i.j < 1 '! t M( R\ &w ' MR MR. 11 ^ys ^x-n 1 ' is MR. fe- ^ 1 ^ys 1 ^Vs MR jx, fc `fe i ii MR- 1V 'ia Cp larit' Ce f! /?rmci-ie>r\. ~i APRBMAk R#R MARRoiR Ap a r t mip s c a r RX/FAFAAk Mf r i/m SP/UA.l C<?RP ^` ia >s. ^ ^ <A >5 ^^ H 1 0 'K* ^ $* ^A. >, *r "! ^ r*> $ 5RP 3r>, 6*' "t" t S 3r c~ DUP040000957 N 25691.01 f V <K k^ ^ \ t? 3 > a K iiVi' 1- s ">- * <3 ' Q ^K $k \N K <5) $ 5 %i ftf Ua -><. k vA V fck ^vs^N o oo krkk: sfi-aj - uoi-f-OJn(JJ j.3j if k ^ NM^ >. ' > **> *>0 ^> iv V^kf "+ . +* <a iS ^ * k- V % '.j s Uj % * i* y k k <) <0 k w '4 k -O k ^" ^ k^ k VJ kk DUP040000958 #3475 $3 ^ q;5Q -S ` 3 k Y> *SJ' v> k\ >' > ^ *v "k Tf' k> xv>^ *:> ^ 7s* k~ %*o C'.S'-.+" k. rzs5\ 7 fN ^ cx *'cSr<s -^>^ Vs7\j?j k :Xt: No. It. V kS k% k>S ^-^4 ^ Vi *& 'k ^ .5 & -3 '>. 7t~ *^*} H^ 'iixo k Sk "k * <s ^ck: ^ ~7VQ -sc ^^ ^ k> sfao ^ ^^ N H.,H^ ^i>S J ^Y) ^V\ kcc< kl. n V> SkS> i ~~Vk ^ u Wj ^^^ !Hk-. '>3-. k^ >^ >> \'kj, % "t: k'A *? ^ 4 1A P7 ..jk-Sck.- DUP040000959 NECROPSY RECORD Material Animal ,A Strain !^Ajf~iG Sex.jxfL. Age Fvriplo^t Diet^,Ms h . -A?y^ No. S&~& .?# ? MR No. /"7C Test <72.qJ? ^x~/tlUUxbZjL Phase. 'bet ___n &u>o-o Observations: />. OA&ty fafAeSt. / /' / Kwrm baja Days |[Test__ Recovery - *jpUUtMA<J!r Weights Initial St?/ SOlIntermediate TL m.Cjlpijr?. 9/0-23~ Killed o2 -/ ~&3 Died Method Survival: dh P.M. Time m . .Change Condition itfD ^ GROSS PATHOLOGY Unless indicated no abnormality detected Histology Recommended: Ym. Nn . Tissue Saved: Yt** L-S Organ Thor./Abd. Br./Sp.C Ht./B.V. Tr./La./Br. Lungs L.N. Liver/G.B. Spleen Pancreas Wf. Grass u93 /,ra 7f>S? H.S1: .7 S 4 > X Micro Organ Kidney T./Ov. Epd./fim. 5.V./F.T. Pr./Ut. Bl./Ur. Es./Sfom. Du./Je./ll. Ce./Co./Re. W. 3.3? bU Gross V Micro Organ Thym./N,F. Thyr./P.T. Adreri. Pih/Pin. Sal./Lac. N./M./F. BO./B.M. Sk./App. Ey/Ea/No/Mo w. .57 e.a&f- <? . 7 // Gross Micro Lj Jl U.W t. p- _St-Gz&j-.. -$* .cr-vyi s^.fr-4-- Cause of Death: H1STOPATHOLOGY cw. Pathologist. Date 3-f-Lj ER-8420 WHITE--PATHOLOGY, FILE BLUE--TOXICOLOGY, MICRO Pathologist. Date _ PINK-TOXICOLOGY, GROSS "DUP040000960 N 25691.02 NECROPSY RECORD Material Animal A/j l j A Strain Sex. a9 .Age Excipient &c/ h . 3473 h o . <re, <??.< MR No. /.7b Test <^7SC/ Phase ~ Dnse o?^>t?r1 'hna/kfr /sS* n^yo | Test--JLk Recovery. Observations; /.* sitAJ>-zA-<A~' J&Ar y (>///j+ts /Jl ij ' ^ 'Jut^CtdU. 'g'jfih /fait, t/jutj : MAtZZf, yXydM^s^fUUAAsr^riY. ^Jry^ (i^jrnvyr>r>auAA.^. m . ^ a j c ^u c l or/yV Weights Initial ^ ____ _ Intermediate / Final -^gyjyp^r ,.&/.-- *U_ f?-y. Si/Aq l /j u 7 yO^OtierTL^ -;<&/> &Ce-^w/> ^ ^Ajyi.s6 /, /^J^WAAxJsrCf T-iRef ml2- KILLEDKillenio*~/-`<& Died __ __ _ .Method. Survival: d /*. h PPliM. Tiimmee. .Change. y General Condition '7%*. - j Uk A^/iX~- GROSS PATHOLOGY ' Organ Wf. Thor./Abd. Br./Sp.C. Ht./B.V. Tr./La./Br. lungs l. N. Liver/G.B. Spleen Pancreas Grass // ./IV.?. ab"'vaal".d Micro Organ Kidney T./Ov. Epd./Fim. S.V./F.T. Pr./Ut. Bl./Ur. Es./Stom. Dv./Je./ll. Ce./Co./Re. Histology Recommended} Yes.._____No .* '* '"* y .^Ho Histology Follows* Yes Ir No W. Gross Micro - Organ Wl. Gross Micro Thym./N.F Thyr./P.T. Adren. Pit/Pin. Sal/Lac, N./M./F. Bo./B.M. Slc./App. Ey/Ea/No/Mo ii ^ 0- CIc aJLa -^-^^ S& ~&JZt ^7%lXl4^cJ?s $4i*<Z$ 7xls<> jtUistU, C*4* Jtii? Crr*pu>4*~M' &hiut*tjdi*' - OiAe^cJcM. _____________ Cause of Death: HISTOPATHOLOGY Q.W, Pathologist __________ Hnto e}-/-.&3. ER-M20 WHITE --PATHOLOGY, FILE BLUE-TOXICOLOGY, MICRO Pathologist. Date PINK-TOXICOLOGY, GROSS DUP040000961 A .a . 3 y. -iiv ai- ________________________________________________________________________ ____________ 0-W' Pathologist Cause of Death: _______________ _______________ ____________________________________ Date HISTOPATHOLOGY ER.8420 WHITE--PATHOLOGY, FILE BLUE-TOXICOLOGY, MOO Pathologist. Date. PINKr-TOXICOLOGY, GROSS DUP040000962 NECROPSY RECORD Material Animal A-txA Strain Sex Cf^. -Age .Diet h .. J.+73 Na.jr&g24 MR No. /70 Test CH&& .4Z&(sb&CA<J?**----- Phase /ttfC6VPf<*j-- Dncp tD tJf>-r) Observations: L j'JjurrsxY-; T a^ZL, v-QiJ.. M th dsu&.X_ KILLED rv,yc j Tmt fZL Recovery /4 Weights Initial --<&?<&_ Intermediate c?/V Final.___ ft.O__ _ u2jg Ref. ti/rx (ft aJx* Killed ,iZ-^r-(>2 Died ...______ Method. Survival: d .^4-.h. P.M. Time. _Change__ General Condition 4K)ft> ROSS PATHOLOGY Unless indicated no abnormality detected Histology Recommended* Yas_ Tissue Saved: Yes J -No. - No - .Organ w. Grass Micro Thor./Abd. Br./Sp.C. Ht./B.V. Tr./La./Br. Lungs L. N, Liver/G.B. Spleen Pancreas n?(CQ h^4~l ~wr Wu? KM, C,b %. / (a1.4 3<UMa\uJ~ t Organ Kidney T./Ov. Epd./Fim. S.V./F.T. Pr./Uf. Bl./Ur. Es./Sfom. Du./Je./ll. Ce./Cd./Re. w*. 3.^2 7 ^3/ Gross Micro Organ w. Thym./N.F. Thyr./P.T. Adren. Pit./Pin. Sal./Lac. N./M./F. Bo./B.M. Sk./App. Ey/Ea/No/Mo C,W fCrCSt CrC Gross Micro Cause of Death: HISTOPATHOLOGY ER.8420 WHITE-PATHOLOGY, FILE BLUE-TOXICOLOGY, MICRO Pathologist. Date. PINK-TOXICOLOGY, GROSS "D U P040000963 NECROPSY RECORD Material Animal Aacb Strain Qjue-eaQ Sex.j A/i a (Excipient h \/ *.3473 . .... No MR No. /7t! Test CH-a Observations: / KILLED ' Killed ,3- /f~ Died Methnd GROSS PATHOLOGY Organ Thor./Abd. Br./Sp.C Ht./B.V. Tr./La./Br. Lungs L. N. Liver/G.B, Spleen Pancreas Wt. "?.// F33 A 3^ Gross 1 Phase A^^TYtiU* . Dose cJL'J O O 7*0 J 9"4l^ /ft/ t/sl^ :' Survival; d *2 h m '' P.M. Time Change , : ?enr' Condition rv,y. Test / Z~_______________ ! Recovery --*----------- Weights Initial Intermedinte 3 __ Finl 3XV is.i! VJuLu v Unless indicated no abnormality detected Micro Organ Kidney T./Ov. Epd./Fim. S.V./FX Pr./Ut. Bl./Ur. Es./Stom. Du./Je./ll. Ce./Co./Re. Wt. Gross }k T7TT Histology Recommended: V _ No - Tissue Saved: Yo* .jQtB _ Histology Follows: Yac i- _ No_ Micro Organ Wt. Gross Thym./N.F. Thyr./P.T. Adren. Pit./Pin. "C7TX iSAO-s^ Sal./Lac. N./M./F. B0./B.M. Sk./App. Ey/Ea/No/Mo Micro 'yi'x&A T -CtzJL ditdJ ( t . dZsj o2 f Cause of Death: HISTOPATHOLOGY AU% Pathologist -. . ...... . .. Date ^ Pathologist, Date DUP040000964 o WHITE--PATHOLOGY, FILE BLUE--TOXICOLOGY, MICRO PINK-TOXICOLOGY, GROSS NECROPSY RECORD Mntorinl jf7a . Animal ,,A.i3l & . ,__Strain @V&- C$ Sex-d-L--Age ytc\p\en\yiO/LiC-X^-L? &~o/ .Diet. No. AT* P*-lC-> MR No. i *7() Test snA~& sUts&SSZCLT*^ Phase AjLCJlMAf- -Dose r3,C$-{?i? Observations: _?v /&t& as-u* 0 KM ! HI (W IaL. DaysjR9co^_3I __ Weights Initial pPO 7 __._- iritermediate <30 4 Final *4t\4. T.I JLu---------- R*f Ctjfa-lixi KnvJZ 2- Died Method Survival: P.M. Tims d Zh,...h m Change SX JJ*'* GROSS PATHOLOGY Unieis indicated no abnormality detected Histology Recommended: Yes_____No Tissue Saved; Yes No Histology Follows: V** Klii Organ Wt. Gross Micro Organ Wt. Gross Micro Organ Wt. Gross Micro Thor./Abd. Br./SpX. Ht./B.V. Tr./La./Br. Lungs L.N. Liver/G.B. Spleen Pancreas J7JJ3 r5U / tf'lf G,i*l \ Kidney T./Ov. . Epd./Fim, S.V./F.T. Pr./Ut, Bl./Ur. Es./Sfom. Du./Je./ll. Ce./Co./Re. 3/ w 3,^.J Thym./N.F. Thyr./P.T. Adren. Pit./PIn. Sal/lac. N./M./F. BO./B.M. Sk./App. Ey/Ea/No/Mo f^rCS^ 0,Cl4 'yc< )L^y3r-} 'h'^( if; / ~ l1 IC- , w( ,J^.(yx(c -> utfh-Caxy.. k.c ) Cause of Death: HISTOPATHOLOGY Pathologist. Date_ -/C-C3 Pathologist. Date: DUP040000965 U20 WHITE--PATHOLOGY, FILE BLUE-TOXICOLOGY, MICRO PINK-TOXICOLOGY, GROSS