Document 3Nb516493XN9JoVXRvR5G2Eg6

' ,, . .. Ammiftti Ouvc 4t*c(t rr. LOW* f. MtHOUKI Qffar fba* CHmI MM2 UUU 24M3 ?5/ Ge/Uilicate <y( AnalyiU Au4t 3rd, 1556 XOWWf - Toxiaalafloal Xaraati^atloa or rydraal a: (ae-c?;. kOMt* Swpla So. 1)4 - T-77 hunt* mjNt X*. T-56-40 SCSI ISOCT*J> XCX M--ala Owlnal Caa^acy, 3. Unas, Uoori. sruna rxxcni - A) OmI ML. la MU OMkUatw ^draal AC aaa Latrodaeod iaao tha ilaaa ~ln of iprafaa-Javla/ JtraAa 3Ma* rata -7 aaaaa of a rabbor cat.Tatar attaabaa to a ajpoiaraie i/rla^. Aftar tbo mcrtiatU UadJanu latbal Aom ma food, groups of rata vara fad at lavala daal^ad ta blaakat tba toalel tjr rp t..araby aafflrla* data for oclealatlaa Oamtti: aara aada for oataard qapUai of toxiclt/ ul riaaara of aalrctad a&laala fro* tboaa aiinMhlaf aaa axaaAaai aaoroaeopleaUf. flu data ara |ira la Tabla Z. t) fl Ml--i latbal Oral tea# for tttotta MUaM Urttaal A^pa Cad M ataaaob taka la ivjlii awuti to loo Zaaliad vfclta aakfcitate arda* ta flad tba lathol MMandMM ana aafci |tr oataard axaxtaaa of todally and U> ruoaca of > *' aaft Attaala tkt aaoaabod aaa azaalaad aMoaeoploally. ra dMa la tadla IX. ey Melip % Sda ItetryUa Za Mtiti adHatod lydnal Af aaa applied ia varying aaooats ta tba slaaaly clippad, lataat Mta af kt Xaalaflt dtlt* raMlta aad tba trtatad mu ooro*ad vita fiaatla abtalda. A Ulktt aollar vaa placed around the aaek f each rabbit ta at--tad ttaa (M taradag taalr ooad rufflsieatljr ta fat at tha application. ObaanaUoaa vaw aada for outaard evidence of toUoltr aad thevtacara of all aalaala toad eaceuabed aaa tiaainad caeroeccp.eallp. _ fba data m foaod In Taala III. TOWOLDMONOOOI932 m Cartifioaka at Aaalyala 2 (*>*) wnmTii menec - (contimed) |) Ikln Zn&katlea la kabbita 0adllatarf''7yd(lul AC aaa applied to tho cloaaly elippad, intact akin of -nr** albino rabtita end observation# ud< over a period of aeveral daya far irritation. Tfca raoulta, baaad am the scorfa^ tocoaique of >alza, ioodard *nd la. y ary (J. of ?feara. A 2xp. Tharapautlei, Tol. 32, So. 4 (loc., 1^44), art eivan ta Table IT. S) Syt Irritation In dabilte 0.1 Kll-iliter of undiluted fydraal AC aaa placed in tue conjunctival sac of the n^it ye c: aeh of throe a.blno rebelta and tho re^uiting irri tatran soorod escorting to jraise, loodard tad Calvary (J. of ?hars. k Sr;. Therapautlae, Tol. '".2, So. 4 (9k.) 19-U;. Data froa eevtral daye obaarvatico are aboaa la labia Y. 7) Yapor Inhalation la lata Four aature aalo rata vara plaead in a natal ehanber of 25 lttaors capacity tad azpoaad far air hoora to aa ataoe.hara of Fydiaul XS vapara produced by eaplratlng the li.uld at rooa taparetare. The sanple aaa pourvd into a throe halo, round, bat to* flaak tad eonprejeed air ;aaa ad over aa orifice, tho looor end of which r*a imeraei 'i tho liquid* 4 g&aat tuba lad fren in* flaak into th ahaabar.--X glaaa aiagnr aaa placed la taa line to break up droplet# and Uloo, aa nearly aa practicable, only ve;crs tc paaa. dir pretatira averagau about 4.4 couade par a^uare inch. The aaiaala tare obaervod far toxic apngte--, and, tinea tharo aara no doatha, all aara hold for tan day# obaervetlon. flea data era ihoan la Table TI. TOTnjn uscairoaiss 6BRN0028M2 TOWOLDMONOOOI933 *kmirti*tifrM TAILS Z u>,, o* -rtaun ic (os 67)* ^ foa juts !-*' v totaal Vo. - lax 1- Mala 2- tela V Mala 4- teaala V teal 6- Mala 7- Mala Paaala 9- Mala lo teal* U- tala 12- teal* 15- teal* 14- Mala 15- Mala 16- Paeala 17- Faatola IS- raeala 15- tala 20* tela n- tele 77?* 260 245 275 220 210 240 235 225 250 195 210 225 200 260 230 215 205 235 245 230 240 tea te. /Sc. 40.0 0.0 40.0 40.0 40.0 *5.0 45.0 45.0 45.0 45.0 . 50.0 50.0 50.0 50.0 ------50.0 55.0 55.0 55.0 55.0 55.0 55.0 tea Sam rad Survived 3a ad Survived Survived 01.4 Survived Survived Survived Mad Mad arrived Survived Survive* Oted Mad Idad Survived Mad Mad Survived Z> 2stZt&c (race par kiloaraa. Survival tlaa aaa overalto ter dlarrfcaa la all aataala aa aibt ba expeetad froa ta ofctala a. ImIbmi aod lattmegf at m three inataavea of aoderate eieenlar tea oaadltte cleared la m to taa daya. aaa the cel/ laportant rlaeeral chaaga notad .&? < S* . 6BRN0Q28M3 TOWOLDMONOOOI934 f ill! XX tes Kuzm urut out aos tr 'fiaum. ac (os-47) * voc unm Aataal So. - 3xz 1 - Kola 2 - Fxsal# 3 - faaala 4 - Bale 5 - Mala 6 - Utl Val^rt Ckaaco Dooo a-./**. 5 3aj* Xftxr ho*laa fate 2.9 2.0 *5 5.5 5.0 4.5 :.2 5.5 7.5 2.9 10.c - 4.0 ft -io.o ft - 4.0 % -14.0 * -12.0 + -10.0 ft tertrH Jacvtrxd Dla4 U hay* i>ia4 -- 6 toyr 01x4 - 11 Oay* 31*4 - 8 Say* axxo&iim - Tfc* lhniiux UUud Oral joax ri** xxa fx4 t* b* 3.5 to 4.3 crux pxr Ulipa. Sarrlral tlax xm alx to tlxrwi Ixyx. XU iiui1* xoxt xx-cfct for #***r*l 4af* after bxlag f*4. Tho* sucxuabloc aontluxi to lax# axigbt uC bxeaa* rmj vxak ktfott dylaf. Tnarx appxarxd to kx xlickt paralyala. . It autepay thxrx ms lixor llacoloration and soJxratx pu; manorj bypx* Ml*. : x s t i ::x rouoiTT c? .Taaxtn, xc (03-47;* si sa tasoamoB 3 ium V*iht Ohaec* feijht Dooo 5 0ay* After >ntea> a*. - *xa ft a. oa. Vic. Joalac fate 1 - Calx 2 - Balt 5 - Bala . 4 - Bala 5 - Balx 4 - Bala 7 -U* 2.12.4 2.5 2.2 2.7 2.4 . 2`* 2.0 5.0 4.0 5.0 6.0 7.5 9.0 4.0 * c.o - 5.0 4 - 4.0 * - 3.0 ft - 5.0 j -10.0 ? 3orxlrx4 3arrlTx4 jurrlTxl 31*4 - 21 lay* 01*4 - 10 Oayx 01x4 - 4 Oajx -1*4 - 12 3*y* 9te ***4-- txthai Jooo by Skin itaxrptloa xxa 4.0 to 5.0 graox par kilacraaL fcrxlMl tlaa m xlft.t to txxnty-OD# day* and wxlgbt loaaxx ru from nftom m tautjr-olcbt r* exat. ffc* aaiaala .rraitnxi ly loxt appxtlte aai xalht. xa4f aao folloaxd by nnatxadin*** aad mu Macular lacoordination, tb* latter kaaoaiac axidao* a ft* lay* bxfora death. It atepay no apxclfie abnorualltla* axra obaarrx* aaeroacapically. 6BRN0028M4 TOWOLDMONOOOI935 AJvuetRor or GBRN002845 TOWOLDMONOOOI936 S'? W 'J 'i fun n * ** xx woo uciuna or 'irouat m (o*^7) * rucxs it im irarafa jalatlaa loaldilr luito Ckbu ..... 64.0 Jt jtwm* TmimWi IHi Ckutar................... 6.5* T. Ulw3 to. - 80 ?> ObimUoM tur.ag Sooaara 1 - tfala 2 - bit 3 - Bala 4 mu mrrlYd Survlrtd Sdff twd hrrlnt hathar mU fiiaocafart, na paaia* at tha worn. iraothlay afcoat aoraal. Bismsism - All mdaals aurrlvad tha six hoara axpaaura aa veil aa tha tan day obaarratiao |tTlTi. tta aoiaala aara aot aarloualy affaotad by tha rapara. IwatMay raaataad rafilar aad irrltailoa au aufflclant to yrodaaa only a allit dogma aC loorlaatlaa aid aallvatioa. tha :oaa1 aacoaa aaa aligbtly mddar tfeaa ami ahaa tha aaiaala vara raaovad fro* tha chaabr bat no odoao aaa itnnil. ippatlta aaaaod to be uaaffacted tha day folloadag axpooura. GBRN002846 TOWOLDMONOOOI937 A* Oral Uka rrAmol tf (0*47) for rta wm S*uad to ~ 52.0 crtna par tn>gr-- #eh a hi# flpua iaAi.Mt.ta that tha eonpoama is praatlaall? lirim whan faA arall? ta rata. fta Uthai Oral 3dm far rmbhita aaa 3.5 to 4*5 *n*a .r kilotfran. Aa Blaijaaa Uthai teas hr 3kla Ahaorrtiaai ia rab.it aaa 4.0 to 5.C jruaa ar kilonran. . m irritation la aahoito conaistad of all#t to vail daflcaA crytsana vlth aa sAiaa for aa arara^a ~**"1 ---- tcor* of 1.5 oat of a yoaaifcla 5.0. Tha ~TTTTai aaa elaasad aa aild skin irritant. fha araraca auini acor* for ^a Irritation aaa 7.5 vu* of i poaalfeit 110. It ana also olaaaad aa a alia tjra irritaat. ata surriraA a atx hour expoaura to Pydrsul AC ra:era which wars foc&d to ha only lightly irritation. th f*lBi*o7 i**.:Jr*|M.- , *-fi : . . J X .. :. , c. . ' r-*.r,-r _ "UJ . roti >_ TT'rrd ,, >. I fJ- pirr" 4toatat.f. Octoi'a, ^ 31 ' <QJ BBRN0028M7 TOWOLDMONOOOI938 \ iounger Laboratories Route 9 -- Box 281 ST. LOUIS 23. MISSOURI PPHh ONE: TlLOEN 6-2540 SUBJECT - Toxicological Inveetigation Of: - Hydraulic Fluid OS-81 - Monsanto Saaple Ho. 1 ' Hydraulic Fluid OS-83 - Monsanto Saaple Ho. 2 Monsanto Project Vo. T-57-1 TESTS COHDUCTED FOR Monsanto Cheaieal Conpany, St. Louia, Missouri February 26th, 1957 fj II 1) Oral LD la Bats J J \\ Each undiluted compound was introduce! \<nto t^^Ponaehs of 3p*ague-2awley strain albino rate by means of^r^bbAfter the approximate Minimum Lethal Dose was fnky7 groanh o\ arts were fed at levels designed to blanket the toxicity range /^hereby supplying data for calculation of the LD-- This was done acgnswyg to/ a aodificatloaNaf the method of Blis3. "* Observations wp^tSSIle fin outward sunptonsAjf toxicity and the vi3cera of selected aniBdaa from thoWwysuccunb^s^was exaained nacroscopically. The data are (shown in TablesS^sail-2^Bl II. B) The Minima L\njal Oral^lfeee For fiahhits Hew Zealand, whi$V***abbrfa were fed orally varying amounts of test compound. The viscera of an^Bd^that succunhed was examined cacro30opically. The data are found in Table III and Table 17. C) Skin Irritation In Babbits Undiluted saaple was applied to the closely clipped, intact skin of albino rabbits and observations made over a period of several days for irritation. The results, based on the scoring technique of Draize, Woodard end Calvery (J. of Phara. and Exp. Therapeutics, Tol. 82, Ho. 4, Dec. 1944). are shown in Table 7 and Table 71. D) Rye Irritation In Babbits 0.1 Ml. of undiluted saaple was placed in the conjunctival sac of the right eye of each of three albino rabbits end the degree of irritation scored according to the sethod of Draize, VToodard and Calvery (J. of Phara. and Exp. Therapeutics Tol. 82, Ho. 4, Deo. 1944). The data are found in Table 7H and Table Till. BBRN002B48 i Thio wuiMaitiol tuport ii not to bo nod io ujr form of adwtiant without writtot TOWOLDMONOOOI939 `To? Monsanto Chernies! tampany, * St. Louis, Missouri Tmingir laboratories Certificate of Analysis - Page 2 (2/26/57) EXPS2I3C2JTAL PBOCED03E - (Continued) E) Tapor Inhalation In Eats Pour mature aals rata wars placed in a metal chamber of approximately ;0 liters capacity and exposed for six hours to an atmosphere of hydraulic fluid Taper* produced by aspirating the compound at roon temperature. The liquid vas poured __ , into a three hole, round bottom flash and compressed air passed OTsr an orifice, . / the lover end of vhich vas Immersed in the liquid. A glasa tube led from the - flask into the chamber. A glass laptnger vas placsd in the line to break up '' droplets and allow, as nearly as practicable, only vapors to pass. ;'i_ The animals vere observed for behavior and, since there vere no deaths, all rata vers hsld for tvo veeks additional observation. The data are shown in Table IX and Table X. ' BBRN0Q28H9 TOWOLDMONOOOI940 ,10$ wnMBM uaemucej. '\.-'pany, St. Louis, Missouri f . Toonger Laboratories Certificate of Analysis - Page 3 (2/26/57) TABLE 1 TEE 01UL LD_q OP 'HIDSAULIC FLUID OS-81* 7 F03 HATS Animal 5o. - Sex 1- Female 2- Female 3- Male 4- Female 5- Male 6- Male 7- Female 8- Female 9- Female 10- Male 11- Male 12- Female 13- Female 14- Female 15- Male 16- Male 17- Female 18- Male 19- Female 20- Female 21- Male 22- Female Eeight Go. 240 210 235 210 225 245 215 200 220 250 210 190 195 215 230 255 200 240 195 205 235 215 Dose Co./*;. 6.00 6.00 6.00 6.00 6.00 7.50 7.50 7.50 7.50 7.50 7.50 8.25 8.25 8.25 8.25 8.25 .25 9.00 9.00 9.00 9.00 9.00 Fate Survived Died Survived Survived Survived Died Survived Survived Survived Died Survived Died Survived Survived Survived Died Survived Died Died Survived Survived Died DISCUS3I0H - The Oral LD._ wa3 found to be 8.60 grass per kilogram with fiducial linits of 6.12 to 9.0^ grams per kilogram. Survival tine vs.3 ovemite to four days. There vao diarrhea, irritability, and nervousness observed. Sons survivors lost as much as 30?& of their starting weight before regaining normal appetite. At autopsy there was liver damage, moderate kidney congestion, and gastrointestinal inflammation. i K' 6BRN002850 TOWOLDMONOOOI941 :Ioj iloasaato Chemical Company, < St. Louis, llisaouri lounger laboratories Certificate of Analysis - Page 4 (2/26/57) TiBLE II THE ORAL 125.. OF 'HYDRAULIC FLUID CS-S5 * . 7 FOR 2AIS Animal Sc. - SeZ 1- Female 2- Female 3- Female 4- Hale 5- Hale 6- Female 7- Pemale 6- Female 9- xale 10- Hale 11- Female 12- Female 13- Hale 14- Female 15- Female 16- Female 17- Kale 18- Hale 19- Female 20- Female 21- Female Weight C 0. 210 220 205 240 210 195 205 215 230 250 190 200 225 165 195 215 240 255 230 210 205 Dose 02* j 27.5 27.5 27.5 27.5 27.5 30.0 30.0 30*0 30.0 30.0 55.0 35.0 35.0 35.0 35.0 55.0 40.0 . 40.0 40.0 40.0 40.0 Fate Survived Survived Died Survived Survived Died Survived Survived Died Survived Survived Died Died Survived Died Survived Died Survived Died l/xdd Died DISCUS3I0H - Ths Oral LD_Q was placed at 34.3 grass per kilogrsa with lower and upper limits of 32.6 to 35.5 grans per kilogram. Survival time was two to seven days. Severe diarrhea, trembling, irritability, and lethargy developed. Weight losses ran to 25^ of starting weight. At autopsy the stomach was gaseous and irritated. The liver was discolored and hyperemic. There was also pulmonary congestion. GBRN002851 TOWOLDMONOOOI942 'To* Monsanto Chemical Company, ' St. Louds, Missouri lounger Laboratories Certifioata of Analysis - Page 5 (2/26/57) TABLE III the jmnami lethal oral dose op 'hydraulic fluid cs-ei* FOE BABBITS Ho. - Sex: 1 - Hale 2 - Female 3 - Male 4 - Hale 5 - Male 6 - Penale 7 - Female 8 - Male 9 - Hale Weight Kg. 2.8 1.9 1.9 2.3 2.1 1.8 1.8 2.3 2.3 Dose Go. / Kg. 0.25 0.35 0.50 0.75 1.00 1.50 2.00 3.00 5.00 Weight Change 4 Days After Dosing 0.0 fa 0.0 f -15.0 fa -10.0 fa -13.0 fo -12.0 fa -20.0 fa -13.0 % -15.0 fa Fate Survived Survived Died--4 Days Died--4 Days Died--7 Days Died--4 Days Died--5 Days Died--5 Days Died--5 Days DISCUSSIOH - The rmim Lethal Bose vaa in the range of 0.35 to 0.50 gran per kilogram. Survival tine was four to seven days. The animals gradually became weak from loss of appetite. There appeared to be partial paralysis after two to three days. At autopsy liver and spleen were congested. There appeared to be blood changes. TABLE 17 THE mraniH lethal oral DOSE OP 'HYDRAULIC FLUID os-85' FOR RABBITS Animal Bo. - Sex 1 - Hale 2 - Female 3 - Hale 4 - Female 5 - Hale 6 - Hale Height Kg. 2.6 2.1 2.4 1.9 2.4 2.2 Dose Go. /Kg. 2.25 3.00 3.50 4.25 5.00 6.50 Weight Change 4 D ays After D osing 0.0 fa + 4.0 fa 0.0 fa - 8.0 fa -13.0 f -10.0 fa Fate Survived Survived Survived Survived Died--5 Days Died--6 Days DISCUSSIOH - The Mini mum Lethal Dose was 4*25 to 5.00 grass per kilogram. Survival tine was five to six days. Height losses resulted from poor appetite. Animals Ho. 5 and. Ho. 6 gradually became lethargic but did not appear to develop paralysis. At autopsy kidneys, liver, and lungs vere all hyperemic. 6BRN002B52 TOWOLDMONOOOI943 Tot Monsanto Chemical Company, St. Louis, Missouri Tjouagar Laboratories Certificate of Analysis - Page 6 (2/26/57) TABLET SEES ZiSITiTICI JS BABBITS AFTER APPUCATIC5 0? 'HYDRAULIC FLUID OS-61* Aninal Ho. Bumerical Eraluation At Tbs End Of 2 Hours 24 Sours 48 Hours 72 Hours 1 1 1 10 2 0 100 '3 1 100 Average 0.6 1.0 0.3 0.0 DISCOSSIOV After two hours, two rabbits shoved barely perceptible redness for an average score of. 0.6 out of a possible 8.0. Bo edema developed. Oremita very slight erythema vas observed on all animals. The residue vaa removed from the skin after tventy-foor hours. Tvo of the animals sere given a zero score on the second day. . Hydraulic Fluid OS-81 was found to be a rather mild skin irritant. i : TABLE 71 Sm IRRITATION IB RABBITS AFTER APPLICATION OF 'HYDRAULIC FLUID OS-83* Ani-ial Ho. Numerical Evaluation At The End Of 2 Honrs 24 Eaurs 48 Hours 72 Hours 1 2 3 Average 0 100 1 11 0 0 I0 0 0.3 1.0 0.5 0.0 DISCUSSION - The average score after tvo hours was 0.3, consisting of very slight erythema on one animal, til rabbits showed barely perceptible redness in twenty-four hours at which time the remaining compound was wiped off the skin. Two rabbits were found to be free of irritation within forty-eight hours. Hydraulic Fluid OS-83 was classed as a rather mild skin irritant. GBRN002853 TOWOLDMONOOOI944 ilo: Monsanto Chemical cl-pany, V St. tools, Missouri Tounger laboratories Certificate of Analysis - Page 7 (2/26/57) iTHtnal Ho. 1 2 3 Average TABLE VII STE IHBITATIOB IB BABBITS AITEB APPLICATION 0? 'HTDBADLIC FLUID OS-31* Buaarical Evaluation At Tbo End Of 1 Hour 24 Hours 43 Hours 72 Hours 120 Honrs 86 2 10 6 4 64 2 2 2 0 8.0 5.3 2.6 1.3 0 0 0 0.0 DISCUSSION - There was slight discoafort shown immediately upon application. The average score after one hour was 8.0 out of a possible 110.0. Moderate erythema and lacriaation with slight edema was observed. The iris was practically unaffected. Orsmite lacriaation returned to normal and the average score reduced to 5*3. Two of the animals had a slight degree of erythema remaining after seventy-two hours. Hydraulic Fluid OS-81 was classed as a mild eye irritant. Animal Bo. 1 2 3 Average TABLE Till ETE IHBITATIOB IB BABBITS AFTEB AFPLICATIOB OF 'HXBHADLIC FLUID 03-85* Numerical Evaluation At The End Of 1 Hour 24 Bouts 48 Hours 72 Hours 120 Sours 86 4 2 12 8 4 2 10 6 4 2 10.0 6.6 4.0 2.0 0 0 0 0.0 DISCUSSION - The degree of irritation was quite similar for both Hydraulic Fluid CS-81 and Hydraulic Fluid OS-83. Mild discomfort developed immediately upon application of Hydraulic Fluid OS-85. After one hour the average score was 10.0 out of a possible 110.0. Moderate erythema of the palpebral conjunctivas, considerable laorimatioc, and mild edema developed. The iris remained clear end the cornea shoved little change. All animal a still showed slight redness after seventy-two hours but all were free of inflammation by the fifth day. Hydraulic Fluid 03-85 *&a classed as a mild eye irritant. GBRN002B54 TOWOLDMONOOOI945 'To: Monsanto Chemical company, St. Louis, Missouri Younger Laboratoriss Certificate of Analysis - Page 8 (2/26/57) T A B L 3 IX IHHALATIOH 0? 'EQEAULIC PLCI3 OS-81' TArOBS BY BATS Average Temperature Inside Chamber .............................. 75*^ P. Average Belative Humidity Inside Chamber ................... 60.0 js AnimalHo. 1 2 3 4 Pate Survived Survived Survived Survived Observations During Exposure Animals continue to move about-- Bo paving at nose or eyes-- Breathing steady. DISCCSSIOI - Ho deaths occurred during the sir hours exposure nor during the subsequent tvo weeks observation period. Breathing and activity in general did not change materially leading to the belief that the vapors did not cause serious discomfort Vueous membranes of the nose and throat shoved only slight inflammation after exposure. Salivation vas not excessive. The fluid vas agitated quite briskly at ten pounds pressure per square inch. However, little or so haxe developed in the chamber atmosphere. It vas possible that saturation vas reached although it vas apparent that the compound does not readily vaporise. GBRND02B55 TOWOLDMONOOOI946 ' la: Monsanto chssriml onmuany, \ St. Louis, Missouri lounger Laboratories Certificate of Analysis - Pago 9 (2/26/57) TABLE X THtar.iTTnw OF 'HYDRAULIC FLUID CS-fiJ* VAPORS BY HATS Average Temperature Insids Chamber................................. 13 y F. Average Relative Humidity Inside Chamber..................... 57*S /* Animal go. 1 2 3 4 Fate Survived Survived Survived Survived Obserrstions During Exposure AM malashow onlyslight discoafort. Continue toexplore cage. DISCUSSIDS - The animals survived the exposure without incident. The behavior pattern wsa very similar to Hydraulic Fluid OS-81. Ho excessive lacriaation or salivation was noted. Activity was not materially reduced. Inflaxaation of the noee and throat was very mild to mild. Air pressure of ten to twelve pounds per square inch agitated the fluid vigorously but appsrently droplets were not carried over into the chamber. The fur of the animals remained dry. As with Hydraulic Fluid CS--61 very little vapor haze accumulated In tha chamber. The vapors of both Hydraulic Fluids ware considered to be only mildly Irritating to rats. BBRN002856 TOWOLDMONOOOI947 ios Monsanto Cheoical^ npaay, ( St. Louis, Missouri lounger Laboratories Certificate of Analysis - Bsc* 10 (2/26/57) SSMKAST - Toxicological Investigation Of tvo new Hydraulic Fluids produced the following results* HTDRAPLIC FLOP OS-31 , mOral LD^g (Bats) -- 8.60 Grans per Kilograa (Fiducial Liaits 8.12 to 5.03 Ga./lg. > :viMintana Lethal Oral Dose (Babbits) -- 0.35 to 0.50 Gran per Kilograa. Skin Irritation (Babbits) -- Bather Mild ffirfn Irritant: Average MaTtaun Score - 1.0 out of possible 3.0. Bye Irritation (Babbits) -- Mild By* Irritant: Average Maxlimm Score - 8.0 out of possible 110.0. Vapor Inhalation (fiats) -- Vo Deaths, Mild Effect. STDB1ULIC FLUID OS-83 Oral LD^0 (Bats) -- 34.3 Grams Per Kilograa (Fiducial Liaits 32.6 to 36.5 Go./Kg.). Miniana Lethal Oral Dose (Babbits) -- 4.25 to 5.00 Grass Per Kilograa. Skin Irritation (Babbits) -- Bather Mild Skin Irritant* Average Maxima Score - 1.0 out of possible 8.0. Bye Irritation (Babbits) -- Mild By* Irritant* Average Marfana Score - 10.0 out of possible 110.0. Vapor Inhalation (Bats) -- Vo Deaths, Mild Sffact. Y0TOG2B LABOBiTOBTSS : y;. . . Bc.sy be >, to !tJ-.'t to lie r.jttl t:r u in C.o- ;*>iv. ``t, *v, : ;*0 ....... c ';`,'rir:!:j nr-. L~ b; divv.!,~?:i ;1, i '* to'.': ^ c; l :2 ... .ft : . ; J.iv . It ; ".v. U-ryr.s, r:;, . ;'.:r r r. ' ''"i :;f . ; -o to b-t I'.'0 TM--} - > bj.V'S! to til' -Toper:- . cl La-Is fc: :.--x GBRN002857 TOWOLDMONOOOI948 Younger Laboratories &ioclw*U6ii.... PUatma&i&ftiti. . . Analyiti i \OUTE 9 -- Box 281 ST. LOUIS 23. MISSOURI PHONE: TlLDEN 6*2540 Gentijjicate SUBJECT Taxicalojrieal Ihvestissticn Of 'OS-95.f Monsanto Ssnpls Number 17 Monsanto Project Nuaber T-564t AttalfUd- February 22nd, 1953 TEST C0KH7CTEE FOR Monsanto Queueal Ccepany, St. Iouls, Missouri DEFTRlMEMT/l PROCEECRZ - A) Oral UiM In Rats The undiluted cenpound was fed rats. After the approximate Mi; fed at levels designed to; calculation of nethod of Elis The viscera o. The data axe pragua-Lav2sy strain albino dete reined, groups of rats were range thereby supplying data for to a codification of the ined aacroacopically. S) Skin Absorption' The sasple was appUsd^undiluted in Taxyin^ anounts to the closely clipped, intact akin cf New Zealand white rabbits an.i the treated areas covered with plastic shields to prevent evaporation. serrations were suds for toxic vymptecs and the viscera of there anlals that succumbed was examined aacroacopically. The data are found in Table U. ' C) Skin Irritation 2h Itobits 03-95 vss applied undiluted to the clipped, intact skin of three albino rabbits and removed after trenty-feur boon with soep end water. Observations were aiade over o period of several dqra for inflanr.atior.. Irritation was scored according to the nethod of Ereiae, noodard and Calvary (Journal of Phare, and Exp. Therapeutics, Vel. 62, No. u, liec. 19hh), The results are given in Table m. 6BRN002858 Thi. nmfirfinr'-* raport io aot to b. nood ia oar lorn ot .dwtuint without writt* TOWOLDMONOOOI949 I Tot Monsanto Chemical 0 sty, St. Laois, Missouri , . lounger laboratories OsrtlflAabe of Anlysls - Page 2 (2/22/58) - T-58-ii EIPr-HPCIJTAi PROCEDURE - (Ooatlmd) D) Eye Irritation 3h Babbits 0.1 KUUiitor of smupla mi plxeod in the conjunctival uc of the right eye of thzoe albino rabbits. The syea ware rinsed with warn iaotcnic saline so1stion after twenty-four hoars. Observations ware made orer a period of several days for irritation. The data* seored according to Demise et al, are found in Table 17. E) Vapor Inhalation la Aits Four mature Bale rata mere placed in a metal clumber of approximately 25 liters capacity and exposed for slic hoars to a concentrated atmosphere of QS-95 vapors produced by aspirating the liquid at rocei temperature. The "p1* (250 grams) was soared into e three holej round bottom flask and canpressed air paaaed over an oxifics, the loner end of which was imersed in the liquid. A rubber tube led from the flask into the ehanber. A glass lnpinrer was placed in the line to break op droplet# and allow, as nearly as practicable, only vapors to pass. The animals were checked for behavior and, si as a thazm were no deaths, all were held for ten days observation. The data are shown in Table V. SOMiAfT - The Oral LDgo 1S-95 was found to be 10,500 milligrams per idlograa with lower and upper limits of 9,295 to 21,865 aiHlgnaea per kilogram. The Minim Lethal Dose range by Skin Absorption in rabbits was 625 to 1,250 milli grams per kilognm. 05-95 was classad as e moderate Mcln irritant. 05-95 was classed as a adld eye irritant. No deaths reaulted when rats were exposed for aiz hours to e concentrated atmos phere of 08-95 vapors. tochcer laboratories ~""" I*.Ztil.i? C;` GBRN002859 TOWOLDMONOOOI950 Tei Hnaadto ttmlcsl C *7, St* LdJ| JOsseurl Touager UWtterfu OsxiifLeate of teilyili Pace 3 (2/2^58) I5W TABLE I THE (SAL LE M OF '05-95' FOB RATS nal Ho* - Sex 1- Male 2- Fanale 3- Female 1*- Female 5- Hale ^ Female 7- Female 8- Ifele 9- Male 10- Mole U- Female 12- Fannie 33- Fwale liin FCttltt 15- Hale 16- Hale 17- Fenale 16- Fenale 19- Fwsale 20- Hale Haight Oa 270 295 210 190 230 205 195 215 230 2li5 185 190 210 225 2U0 220 215 200 190 395 Eoee He./*5. 9*000 9,000 9,000 9,000 9,000 10,000 10,000 10,000 10,000 10,000 11,000 11,000 11,000 31,000 11,000 12,500 12,500 12,500 12,500 12,500 Fate Survived Survived Survived Survived Survived Died Survived Survived Died Survived Died lied Survived Died Survived Died Died Died Survived Died 13CESSION - .' The Orel LDM w placed at 10,500 nmigrena per ldlociea with lower and upper Units of 9,295 to 11,865 Pilltgrana per idlogran* SurrlTsl tin was overnight to three days. There was diarrhea, salivation, tremors, id ease* At aotopsy the gastrointestinal tract was gaseous and inflamed. There was liver discoloration due in part to congestion* ' GBRN002860 J' TOWOLDMONOOOI951 To I JiSBUBtO OiliCSl MBJt St. | It] aamrl lounger laboratories Outlfloate of Analysis - Page 1* (2/22/58) - 7-584* TABLE II THE NZKIM2H ITTHAL CBE OP '03-95* E7 3 EDI ABSOHPTI Df RASBITS Jnlnal So* - Sex 1 - Frauds 2 - Female 3 - Male 1* - Mala 5 - Male 6 - Faaals 7 - Male Height l. 2*3 2.1 2*6 2*6 2*1* 2*1 2.5 Daaa ft./ft. U5o 625 1*250 2,500 5#ooo 7*500 10,000 Weight Change 5 Eeya After Deslag ft. - 0.2 - 0,2 - 0.3 - 0.2 - 0.2 - 0.1* - 0.1* Fate Survived Survived Had - 11 Eaya Died - 5 Bays Clad - 5 Bays Bled - 1* Bays Bled - 3 Days EISCDSSiaf - The JtLnlaoa Lathal Doee zenge ni found to be 625 to 1,250 nlUlgnns per IdJLograa* Survival tdaa eaa thzee to eleven day*. Appetite km aoon affeefeed nsulting In veigit lasses. Tbla eaa about the only trade syaptaa for tea dqrs. MeaJraess and lethargy non noted theraafter. Violent eacTulalooa developed la teo of the airlaala aeveni hours before death. At autopsy there sere extensive hanorrhagle anas la the lunge and Moderate lddnay congestion. \ BBRN002861 U- TOWOLDMONOOOI952 Tei Monsanto Chwilnl G. /acrt St. Laois, Missouri. lounger Laboratories Qsxtifieate of Analysis Page $ (2/22/58) T-5B-J* TABLE IH SK3K IHHETATXW Hi RAF1'ITS AFTER APPLJCATICH OF os -?5 Aninal Ember 1 2 3 Average Naaerle&l Evaluation At The End Of 2 Hoars 2k Hours 1*8 Hoars 72 Hours 120 Hoars 2 3 2 11 232 21 13 2 11 L.6 3.0 2.0 1.3 1.0 riscuss: err - After two hoars there was slight to sell defined erytheoa with no sdaoa for an average score of 3*6 oat of a possible 6.0. Overnight the average score increased to 3.0 an the basis of Bore redness and elicit adsea. The application was removed in twenty-four hours bat the irritation decreased rather slowly. Slight erythsna was still present on all anlaals on the fifth day. 05-95 was classed as a moderate skin irritant. GBRN0Q2B62 A" TOWOLDMONOOOI953 Hot Monsanto Owl ml .paay, . St. Louis, Missouri. Yeangar laboxmtoziee Certificate of Analysis - Pag* 6 (2/22/58) - T-5W* T A 2 L E 17 E IE UL-XTATICN IN PJQ3ITS AJTER APPLICATICR CF OS-95' Animal Umber 1 2 3 Avenge Nuasrieal Evaluation At The a*l Of 1 Hour 2U Hour* led Haora 72 Hours 120 Hours 12 8 ii 2 0 10 6 U 0 0 12 6 h 2 0 11.3 7.3 4.0 1.3 0.0 nsrossia? - There me nlid lanedate disccofoxt ahcrvn upon ^plication. The average score after one hour me U3 out of e possible 110.0. Irritation consisted of noderate erytheaa of the conjunctives with aild edeeie end lecziaation. The details of the izie were slightly obscuzed due to sane congestion. The latter condition tepxoved overnight resulting is an average score of 7.3* <* eninal was free of Inflauostian in seventy-two hours ana ell weze given e score of zero in five days. 03-95 ms deseed as a aild eye irritant. GBRN002863 TOWOLDMONOOOI954 Tot Hsnunto OnMical pony, St* tadSf HLaaouxt Toonfor laborstoxiee Certificate of Analysis Page ^ (2/22/55) - T-58-ii TABLE 7 INHALATION CP *0S-9$* 7AP0HS BT BATS Anrexege Taepexatuxe Inaida Chaster * Average dilative Hnsitttty maids Charter * * * * * Jaount Of OB-95* 7apoxaed * 76, d3 F* 59m5 % 6*U Oxana Animal No* - Sax 1 -Kale 2 - Hale 3 - Kale U - Kale Fata Survived Survived Survived Surrlred Oboexvaticra Baling E^osuxe Little linedLata reaction Activity abort nozsaal Aalaals cantirue to explore ehstber Escfozt alight after four botixe. asctssioN - The rate survived the Mix hoar exposure with so afteznath of branchial rales or other evidence of respiratory injury. Activity was not affected to any noticeable extent. The anlaals remained ateady and ware observed eating and drinking at intervals* Nasal nd ocular irritation was not auffLdant to stimulate a discharge. 6*ii areas, equivalent to 2*5 par oent of the sarnie, was vaporised. Considerable agitation mi Maintained at a pzeaeure at thzee pounds per square inch. However, the chnbar ataospbaza raaained quite clear with only a very allgit hast detectable by zaflaetad light* It waa concluded that a concentrated ataosphexe of OB-95 vapors was only slightly irritating to xsebs xqpoaad for aix houra* 6BRN002864 TOWOLDMONOOOI955 Route 9 -- Box 281 Y Lounger aboratories Ce/Mpccdz of AnaIlfM,BioeJtettuiU. .. Phatmacol&fi&U. . . Atfah^ii ST. LOUIS 23. MISSOURI PHONE: TlLDEN 6-2540 the raricnr cf the thermal zfcohpceitit, ?;q:ucts cf PTOtAUL 625* Study Conducted For MOISANTO CH3UCAL COMPACT, ST. LOCHS, MISSOURI imovcCTig? The experinent vu designed to dotensice the efeet*unBB*JfctoQ5gfcibiy rate when ex posed to fog of thenr.nl decomposition ^t^Zttcts propped by d^p^iing PT! RAX 62$, Lot A-l5(, e predict of Macsentp ChB^ca^tapeggy^'on a esrfhce heated to a tem perature of 2000 Fahrenheit//variouBY^eh^tLes of fog were generated for different groups r AL PROCEDURE Half of a flfteanNihah McP^ndl high tasperature combustion tube (inside diaaeter eev*j>eighth'a inch, nco-porous vitreous material) was wound with special sixteen gauge nlcicel-chrcsilum wire. The wire waa attached to a variable transformer for corn.rolling temperature. After being wrapped in asbestos paper, the tube was insulated with four lnehes of Mineral wool and then surrounded with a container Bade of asbestos board. n tube was clasped at m angle of appxcodjaately ?0 degrees with several inches of tha unwound end protruding fae the eontainer. A thermocouple waa inserted to the oarrtar of the tube and tha tsapereture assured by an indicating pynanater. At the upper end of tha container two openings ware made; one large enough for a sell funnel to be ineerted. The liquid to be volatilised was dropped frae a tairet This coofidutUl report a* not to bo vood in any fora of idvtrUBOi witiwt wntteo porouaMon f* EXHIBIT 1 K-HS GBRN002865 TOWOLDMONOOOI956 lilt lUUCIIX OF THE 3HEK1UL DECOMPOSITION PRODUCTS OF PTT.RAUL 625 To* Mmsento Chicle*! a my, St, Louis* Missouri Lounger Laboratories Certificate of Analysis - p*ge 2 at a measured rets* thrwigh the funnel to the Inner surface of the heated conbustion tube. The tube was slanted to prevent the drops fra falling through and at the sane tine allow than to spatter against the sides* slaking for rapid volatilisation. Curved* three-fourths inch copper tubing was attached tp the other onening, The tubing rets to s height of tvo and cr e-half feet above the ecnbustlon chamber and then returned about the same distance to a one liter flask fra idiich an opening led into a five gallon glass Pottle connected to a netal inhalation chamber of seventy liters capacity. Animal were placed In the chamber* the chamber sealed* anc connected tc a vacuum pusp with rubber tubing. The fluid was dropped at a measured rate onto the inner surface of the coabuetion tube heated to 2003 F. Sufficient suction was supplied by the pump to pull the combustion products through the copper tubing into the liter flask and firs gallon bottle and then into the exposure chamber. Fra here the fog was drawn into an air trap and a calrim chloride trap attached directly before the veeutn pmp. Ho cooling bath was used for the fog; temperature reduction was achieved by passing the combustion products through the copper tube and the five gallon bottle before entering the chamber. It was desired to expose the animals as nearly as possible to the fog as generated. The liter flask removed esoe solid particles of combustion. Supplemental air for the animals1 oxygen requirements was supplied by an air com pressor and introduced into the five gallon bottle for mixing with the contusticn products before entry into the exposure chamber. The flow of filtered and dried sir was controlled by means of a calibrated rotameter. QR3UP At STP05UKE TO MOfERATE HIST (SH HOPflS TOTAL) Sight mature male rets ware exposed for one hour three days per week for two weeks to s moderate ccnoentretlon of PIDRAtlL 62$ volatilised at 2000 F. concentration GBRN002866 TOWOLDMONOOOI957 TH" TOIICITr OF THr THB-hAL iCOH?OSITION PTOL'UCTS OF *PZLiiAi;i 625' Tei Monsanto CbUcal Ct any, St* Louis, Missouri lounger laboratories Certificate of Analysis - Pan* 3 vas dearly evident In the chamber but not sufficient to obscure the animals. The fate of the ninala is shown in Table I. OHXP Bl EXP3-VRE TO HEAVY CONC-ymTIOTI OF MIST (HFTSFK XTTUTSS TOTAL) Eight nature male nta vexw exposed for fifteen ninutes to a heavy concentration of PTERAUL 625 cist produced by volatilisation at 2000 P* The concentration was practically as heavy as obtainable. The animals in the frcnt of the ehanber were nearly obscured. The data cn the animals is shown in Table II. PROOF Cl SPjnURS TO HTAVT COKCEITRATIOS OF KIST (OWE HTCH TOTAL) Eight mature male rate were exposed for one heur to a heavy concentration of PTT'RAUL 625 Bist proceed by volatilisation at 2300 F. The concentration was practically as heavy as obtainable. The animals in the front of the ehanber were nearly obscured. The results are shewn in Table HI. Figure 1 -- Inhalation Chamber And Equipment For Gene rating Mist Figure 2 -- Close-Dp Of Inhalation Chamber Euring Generation Of Moderate Concentration Of Mist Figure 3 -- Close-Up Of Inhalation Chaaber During Generation Of Heavy Concentration Of Mist ' (the material in this report ia to be used in development of Che product and may be given to responsible rales contort*, but it is.not to be used by iVn in edwv^irp. ecThe sourca of this iratoriol i.i r.cc to c'r.-vh'r J nni. i n orp#: .^* in formal publications. No ex-TV. o:a ...... r* \ may b? him'i without 1 ho c* * '" ' *' * ment in St. Louis. Cnaloujero' ir*ri!iri'.!rT.>*'^n" '*1^J? toxicity are to be referred os before to Medical Ltp meot in St Louis for reply. GBRN002867 TOWOLDMONOOOI958 THE TOLL cm CF THE THEfKAL rCaK?CEI7IC8J PRODUCTS CF 'PTE HAUL 62S Toi Monsanto Qmmical Oa ay, ` St* Louis, Missouri lounger laboratories Oertifleate of Analysis - Page It TABLE I EXPOSURE TO 'PTDRAUL 625* MIST (M7~V.TT CWCECTRATICN) ONE HOUR TAILY, THREE EATS PER WEEK FOR TWO WEFJB (SH HOURS TOTAL) Atsrage Temperature Inside Chamber Avenge Relative Humidity Inside Chamber *......... Volatilisation Rate ........... .. Supplemental Air Supply ................................ .. 66*0 F* 73,5 X 6*1 KL./Hour (Equivalent to 8*2 da./Hour 6*0 Ilters/ftLznxte Animal Number Starting Weight Gb. Weight Chsnge 2 Weeks After Lest Exposure da* Weight Change It Weeks After Last Stposuie da. 1 235 - 10 2 250 0 3 2lt0 - 25 h 260 5 5 2U$ 15 6 230 0 7 21*5 - 10 6 255 -35 0 15 ---- 20 ---- 10 5 0 Fate Survived Survived Died - 21 Days Survived Bled - 18 Days Survived Survived Survived nscussicw - Ho deaths resulted during the exposure tins although two of the mts died eighteen and twenty-one days after the final axpoauxe. The fog produced a modante degree of irritation each time, most of which, outwardly at least, appeared to here cleared up by the time for the next exposure two days later. There was salivation, natal diachargs, seme instances of irregular breathing, and modsrate lethargy. The animals were reasonably steady whan moving about the chamber and sons appeared la danger of collapse when removed* Temperature and tumidity were higher than normal in the dumber due to the steady* influx of the mist* This contributed easewhat to the disconfort of the animals. Activity beteem azposuxms rwalned about normal* Tbe tax of the rmts was damp frsa condensate after eaeh erqpoeure* Several of tbs animals developed sniffles as GBRN00286B TOWOLDMONOOOI959 THE TOKICnr OF TR~ THERMAL PECCtf'a'ITION PT02UCTS CF PT2RAUL 625 Tot Monsanto Qanieal Cc B^r, St. Louis, Missouri lounger Laboratories Oartlfleato of Analysis - Page 5 the experiment progressed but respiratory inflaamtian did not reach the stage of bronchial nlea. The majority of the rate lost weight for approximately two weeks after inhalation was concluded. Four weeks after the final exposure, all rata with the exception of the two that died at eighteen and twentyrone days, had gained weight and appeared to be in healthy condition. The animals that suecinbed beejme emaciated, developed eolde, and gradually lost weight. A streptococcus organima was isolated from the pulmonary tract of one rat. It is impossible to state whether exposure to mist was a direct cause of death in both instances. It is likely that this, in cmbination with high tonicity, were contributing factors. GBRN002869 TOWOLDMONOOOI960 1HE TOXIC ill U Uu. .................. ~ Tot Monsanto Chwieal C any, St. Louis, Missouri lounger Laboratories Certificate of Analysis - Page 6 TABL! II EXPOSURE TO PT2SAUL 625' MET (HEAVT CCNCEWTRATICN) F FIFTETJ! KUTUTES Average Temperature Inside Qianber ............ Average Relative Humidity Inside Qianber ...... Volatilisation Rate ........................................ Supplemental Air Supply ....................... 1.5 F. 65.0 2 13.9 KL./Hour (Equivalent to liu7 Cku/Hour 3.5 Liteie/KLmte Animal Number 1 2 3 h 5 6 7 6 Starting Weight G m 215 235 220 2U0 210 230 235 2hS Weight Change After 2 Weeks Os. 15 10 20 5 25 10 IS 0 Observations firing Exposure Considerable discomfort after a few minutes -- CobiouB nasal discharge with sane lacrimatlcn -- educed Activity -- a obscured except in front part of eage. EI5CUS3ICN Ko deaths resulted free fifteen minutes exposure to a saturated atmosphere of PITHAUL 625 thermal decaspositlcn products. Reduced activity and irregular breathing were noted when tbs animals ware removed from the chamber. They veze not in danger of collapse. Examination thirty minutes after exposure showed a cessation of nasal discharge but moderate edrna of the nasal mucosa and redness around the eyes. Tbs had gained in Height when neighed two weeks later. They appeared normal by outward obeervatian. . 6BRN002870 TOWOLDMONOOOI961 THE Ton CUT (F THK THERKAL CECCHPoemW PHOXCTS OF PIDRAUL 625 Toi Manaento Overt cal C. /wyt St. Louis, Missouri longer Laboratories Certificate of Analysis - Pegs 7 TABLE in EXPOSURE TO PraUUL 625* KTST (HEAVE CCKCENTHATICN) TOR ORE HOUR Avenge Tbnpentun Inslds Chamber......... . Avenge Hslatlre Hmidity Inslds Charter Volatilisation Rats ..................................< Supplemental Air Supply .< 6iu0 F. 69.0 % 10.9 ML./Hour (Equivalent to lii.7 da./Hour k$ Liten/Jtlnsrte Animal Number Starting Weight Oa. Weight Change After 2 Weeks (to* Observations Earing Exposure 1 205 2 . 220 3 195 h 220 5 235 6 215 7 21*0 8 225 15 5 -5 10 0 $ 0 10 Salivation and nasal discharge in a few minutes Breathing gradually becaaing short and irregular -- Considerable activity for 10 to 15 minutes -- Definite weakness within 30 Minutes All animals at the point of collapse when removed free chamber, EISCESSION The heavy concentration of acrid fog was nearly fatal to the animals exposed far one hour. They were Is a eend-eematoee stats whan taken fren the char.ber. The majority sere on their fast within thirty Minutes but ahowad marked weakness. Breathing vas difficult and irregular. Considerable improvement was noted overnight. However, lethargy and poor appetite were evident for several days. After two weeks all animals were still alive end acting normally with, one exception. Tbia mlnal appeared unthrifty but tbs condition did not uppear to be confined solely to the respiratory tract. 6BRN002871 i' TOWOLDMONOOOI962 Tot Monsanto Cheaical Ca . -ay, St* Louis, Missouri ' lounger Laboratories Certificate or Analysis - Page 8 SlUiAI . FTPRAUL 625 was volatilised by dropping the liqvid onto a non-poroua, vitreous surface hasted to a tenperature of 2000 F. The thezmal dseosposition products vers drawn into an inhalation charter and groups of rate exposed to various eaneentrations of the mist. The results vers as follows * 0-CT? At TXPTVir T) Y.vZV,7? KIP? (SIX Hd'ftS TOTAL) Considerable disccrfort, irritation, and lethargy resulted fren the exposures, but there were no deaths until eighteen and twenty-one days after the final exposure when two of the eight antaals auccunbed. 0H00? Bi EXPJPHHT 7.j T'ATT C^C^TRaTia? 07 KI5T (FIFTEEN KISCTES TOTAL) fifteen ninites exposure to e heavy concentration of sist produced copious nasal discharge md lacrtaation, indicative of irritation* The entasis showed sene weakness when moved fm the cheater tut All survived. 0T?0D? Cl EXPO^'fF* TO ?F?A7T C3WCE?rraAnOS OF HIST (0>.T: K0P3 TOTAL) Che hour exposure to a heavy concentration of nist resulted in weakness to the point of collapse In all entasis* Breathing difficulties gradually disappeared ss the pnin\M gained strength* After two weeks they appeared noreal with the esaeption of one antaal* The pH of the condensate fren the volatilised PTTiUUL 625 was in the range of 3*$ to lu$. * T0Q8QZ.1 LABORATORIES 8sptsnbar 29th, 1958 BBRN002872 TOWOLDMONOOOI963 Younger Laboratories iiiocUtmiiiL... Phafimacatoqiiit. .. AnalfUi Route 9 -- Box 281 ST. LOUIS 23. MISSOURI PMONK: TtUDCN 8-2540 Gefttilicate AnalyML Ostober 20th, 1958 SUBJECT - Toxicologioal Bxveetlgatlon Of 08-95. Monsanto Sample Bober 102 - let 7500.-3677? Monsanto Smpls HUmber 17 - Lot S-59 Monsanto Project Number 1-58-29 BESTS CCRDOCTED POE - Monsanto Ooniesl Caapany, St. Louis, Missouri ZSEHSQIJL PROCEDURE -- A) Skin Absorption MZD (Rabbits) The undiluted compound van applied in varying mounts to the closely dipped, intact Mdn of albino rabbits and the anInals placed in wooden stocks for eight boors after which the trade was wrapped In plastic strips and the aniaals returned to lndivi&al cages. Observations were node for taxis sjnptcms and tho viscera of selected aniaals fron those suectnUng was exaalnsd aaeroscopieally. The data are shown in Table X. B) Skin Irritation (Rabbits) .' 0.1 Milliliter of undiluted 08-95 was applied to the clipped, intact skin of albino rabbits and observations node over a period of several days for irritation. The results, scored according to Braize, Woodard and Calvary (Journal of Phasa. and &cp. Biorapeutlcs, Volume 62, 377 (l?2ib)), are theta in Table II. _ f/j)XDUNjER LABORATORIES L f Lc Bit FRED M. VJWim TOWOLDMONOOOI964 To: Monsanto Chemical t,. .pany, St. Louis, Missouri lounger La.boratori.ea Certificate of Analysis - Page 2 (10/20/59) - T-58-29 TABL2 Z faces? ap os -95' bt sra absorption IN RABBITS Sample Applied Dbdilnted Weight Dose Animal No* - Sex Kg* Mt. SAMPS 102, Lot 7501-3677 1 - Kale 2 - Female 3 - Female k - Kale 5 - Male ' 6 - Hale 7 - Female 2*1 1*8 2.0 2U 2.3 2,h 2*0 1000 1500 2000 2000 2500 2500 3500 SAMPI2 17, Lot s-5? 1 - remale 2 - Male 2*3 2*6 3 - Kale k - Mile 5 - Fsnale 6 - Female 7 - Male 2.5 2.3 2.2 2.1 2.6 1000 1250 1250 1500 1500 2000 2500 Weight Change 5 Daye Later Kg. >iti . Fate . 0.0 - 0.2 - 0.3 - 0.1 - 0.2 - 0.1 - 0*3 Survived Survived Died - 7 Days Survived Died - 6 Days Died - Ih Days Died - 5 Days - 0.1 0.0 - 0*2 - 0.3 - 0.2 - 0.2 - 0.3 Survived Survived Died - 17 Cays Died - 9 Days Died - 7 Days Died - 7 Days Died - 6 Lays discussion - There was one death and one survival at 2000 milligrams per kilogram on Sample 102, lot 7500.-3677* Survival time ranged from five to fourteen days* Gradual loss of appetite with Increasing lethargy and weakness developed* On Sample 17, Lot S-59 there was one death end one survival at 1250 milligrams per kilogram* Survival time waa six to seventeen days* Toxic symptoms were very similar to those already described* At autopsy there appeared to be degenerative changes in the liver by macroscopic examination* Pulmonary hyperwia was also observud. BBRNd02874 I TOWOLDMONOOOI965 Tor Monsanto Chemical 6. yany, St, Louis, Missouri lounger Laboratories Certificate of Analysis - Page 3 (10/20/38) - 1-58-2? TABLE XX SXZH ZREZXAXXCN IN RABBITS AFTER APPIIC4IICN OP * os-?5' Sample Applied Undiluted Animal Number Numerical Evaluation At The End Of 1 Hour U Hours 2k Hours lid Hours 72 Hours 120 Hours SAHPIE 102, Lot 7501-3677 1 00 2 1 1 0 2 01 3 2 1 0 3 01 2 2 1 0 Average - 0.0 0,6 2.3 1.6 1.0 0.0 - SAMPLE 17, LOT S-59 1 2 3 Average 01 3 2 21 01 2 2 10 01 3 2 10 0.0 1.0 2.6 2.0 1.3 0.3 DISCUSSION - . No irritation was observed on either sample one hour after exposure. Two out of three animals on sample 102 showed barely perceptible erythema after four hours for an average score of 0.6 out of a possible 8.0. Overnight there vas well defined erythema with one instance of Blight edema increasing the average score to 2.3. Removal of the application reduced the irritation to barely perceptible redness on the third day. There was practically no difference between the two samples as the data in the . table indicate. The average twenty-four hour score for numbar 17 was 2.6 as compared to 2.3 for number 102. The two samples of 06 - 95 were classed as mild to moderate skin irritants. Jr*?. ;fnl th!> rT*r* !s tn h* " -'* st is "... fr IiNn .S.-....... . >: - IN. .! : i . . ' l.- :> n.--.:;.... lc t:. -I >vr i.-.n, j . . .< . d"v-!3r,fi.nl ,.f ' .I'' .' ` V ' . I; . t .1- QBRN002875 TOWOLDMONOOOI966 Tot' Monsanto Chemical C pany, St. Louis, Missouri lounger Laboratories Certificate of Analysis - Pago k (10/2C/5S) - Y-53-2? SDMttHT -- She Minima Lethal Dose range by slda absorption in rabbits was determined on two saaples of 08 - 95* ' Maabor 102, Lot 7501*3677 fare a range of 2000 to 2500 allllgrans per kilogram. Natber 17* Lot S-59 gave a range of 1250 to 1500 milligrams per kilogxaa. Both samples wars classed as aild to noderate slda irritants. The average maximum score for amber 102 was 2.3 cut of a possible 8.0 in twenty-four bours. Number 17 scored an average of 2.6 after the same time interval. ' GBRN002B76 TOWOLDMONOOOI967 Younger Laboratories &iocUeu4l&. .. Pha^maaolaqiiii. . . AnaLfiU Route 9 -- Box 281 ST. LOUIS 23. MISSOURI PHONE: TlLDEN 6-2540 Ge/itiUcaie oj Analtftii. THE TOXICITY OF THE THERMAL DECOHPOSITIOH PHOEUCTS OF 06-9$' Study Conducted For MONSANTO CHEMICAL COUPART, ST. LOUIS,- KESSOURI IXTROnUCTIOK The experiment w designed to determine the effg rets when ea posed to fog of thereal daocnpoaitlan sed by'a^ppinc OS-95# Lot 7SCDL-3679 product of Monsanto on a rorfaoe heated to a tpenature of 1000 sitlea of fog vers generated for different groups AL PROCEDURE Half of s high tnpeture eanboetlon tube (inside disaster seren-eighth's Inch, noo-poroua vitreous naterlal) use wound with special sixteen grege dclal^hroBlm wire* The wire wee attached to a Tazleble tzanafoxner for controlling twperwturw. After being wrapped In asbestos paper, the tube was Insulated with, four inches of amoral wool and then surrounded with s container ads of asbestos hoard. I The tube was elsaped at an angle of appreodastely 70 degrees with eevwral indies of the unrcend end protruding fxsn the oeBtalaar. A tbszaoeoupla was inserted to the canter of the tube end the taqpermturo Measured tgr an indicating pyrwater. TUi ccn&hntU raport io mot to bo GBRN002877 w EXHIBIT I TOWOLDMONOOOI968 THE TGnCITT " THE THEMUL rECCHPOEITla* PTCTTS W * OS-95* Tel Menemto Cbaeieal flnepahy. St. Louis, Waaouii Enagsr Inbomtoriea Certificate of Jtaelyaie - Page 2 it the tipper end of the container two openings wn made) one large enough for a sail funnel to be inserted. The liquid to be volatilised was dropped tram a burette at a manured rate, through the funnel to the Inner surface of the heated eonbuetiflo tubs. The tube was elmted to prevent the drops from falling through and at the sme tine allow then to spatter against the aides, making for rapid volatilisation. Cuived. three.fourths inch copper tubing wee attached to the ether opening. The tubing rose to a height of two and one-half feet above the eonbuetion chanber and than returned about the acne distance to a one liter fleak trm whioh an opening led into a five gallon glass bottle eonneeted to a natal inhalation ehmbar of seventy liters capacity. indaals were plaoed in the chamber, the chanber sealed, end eonneeted to a vaeuia posp with rubber tubing. The fluid was dropped at e measured rate onto the inner eurfsee of the cenbustlon tube heeted to lOOCP ? Sufficient auction was supplied by the ptnrp to pull the eonbuetion products through the copper tubing into the liter flask end live gallon bottle and then into the exposure chanber. Fzm here the fog was draw into an air trap and a ealcitet chloride trap attached directly before the vaeutn punp. Mo cooling bath wae used for the fog) temperature reduction aae achieved by passing the eentauetion products through the copper tube and the five gallon bottle before entering the chanber. It was desired to axpoae the animals ma nearly aa possible to Ihe fog as generated. The liter fleck woved earn solid particle* of emfaustion. Supplemental air for the aalaals* oxygen reqnl wants was supplied by en air eenpiesaor end introduced into the five gallon bottle tor airing with the eoetustion products before entry into the exposure chamber. The flow of filtered and dried air wee controlled by aeena of a calibrated roteaeter. 6BRN00287B TOWOLDMONOOOI969 THE TOIICITT ' THE TSZMAL FTCOPPOSITION paorT~TS CF 08-95* 4 Tos Monsanto (Tisslral Onnpany, St. Louis, Missouri Ibunger laboratories Certificate of Analysis - Pag* 3 PROP? At TXPOPPHE TO MODERATE MIST (SH HOURS TOTAL) Eigit nature male rata mr axpoacd Tor one hoar three days par week for tiio weeks to a moderate to moderately heavy concentration of 03-9$ volatiliaed at 1000 F, Tha canoentretian of fog was sufficient to partially obaeura the anisela at a depth of six inches within the ehber. Those at the rear of the chanter (a depth of eightom to twenty-four indies) wore all but obscured. Sis fata of the animals is shown in Table I. OROOP Bi EEPOSPFC TO H-ATt CO CTHTRATTON OF NIST (FIFTEEN KIKOTES TOTAL) Eight nature nala rata ware exposed for fifteen minutes to a heavy concentration of 06-9$ nist produced ty rolatilication at 1000 F* The eaneantraties was as heavy as obtainable* The anlnals In the front of tha clumber ware nearly obseured* Those at a depth of six inches were completely obscured* Tha data on the animals is shown in Table II. QROPP Ci HPOBPHE TO HSAVT CONCEOTRACCK OF HIST (CNS HJ7R TOTAL) Eight nature male rata vara axpoaed for one hour to a heavy eoneentmtlon of 06-9$ nist prodioed ty volatilisation at 1000 F* Tha concent ration was as heavy as obtainable* The animals in tbs front of tha chamber ware nearly obscured* Those at a depth of aix inches vara completely obscured* The results ere ahotn in Table m. * BBRN002879 TOWOLDMONOOOI970 THE TOIICrTT ' ' TFTF TTOWL DECCHP03ITI0N PHOnpr-S OP* '05-95' tot Monsanto Chawical Caqpahy, St. toola, Jttseouri Ibunger leboreioriee Certificate of Analysis - Page U TABLE X EXPOSURE TO *08-95* MIST (K03ERAIELT HEAT I CGNCENTRAfIQR) ONE HOUR EAIU, THREE CATS PEH WEEK FOE TWO WEEKS (SIX HOURS TOTAL) Aveng* Tenpersturs Inside Chaster . Avenge Relative Baniditgr Inside (hasher......... Volatilisation Rate .................................... ................ .. Supplasieotal Air Supply 75.5 F. 56.0 % 6.0 XL./ Hoar (Equivalent To 8.1 CM./Hour) 6.0 Litare/Minute Member Starting Weight On. Weight Change 1 Week After Last Exposure Cta. Weight Change 2 weeks After Last Bqposuxe Cfc. 1 215 - 5 2 230 - IS 3 220 - 10 U 235 5 5 225 0 6 no - 10 7 2U0 0 8 225 0 0 - 10 -5 10 0 0 5 10 Fate Survived Survived Survived Survived Survived Survived Survived Survived DISCOSSIOM - Teo weeks after the last one hour exposure ia the series of six, all animals were alive and preetieally nonal In outward appearance and behavior. Breathing was quiet and regular with no nasal discharge. Six of the eight wilaals ware either alntalnlng their ctarting weight or had galnad slightly. Appetite of the rwuln- ing two Inals had isproved over that shown the first week following the last azposuxe. Fog from 03*9$ deoaipossd at 1000 F. ewraed eonaidarebla dlscenfort within a few slxsites. Msaal discharge, salivation, aoderate laeriaation, aid rapid breathing followad by breathing waa obaaxved. Tha anlxala ware usually quits active for ten to fifteen nlnstea after whieh ttey been lethargic and ohangad poeitian in the ehanber less often. BBRN002B80 TOWOLDMONOOQ1971 i- THE TOXrCITT ' THE THERMAL IECOHPOSITIOI PW "TS OP '0-95' Tst Manaanto ffilral Gcatptiiy, St* Louie, KLaeourl banger LeboiatoAea Oertlflncte of Analyeia - Pag* 5 Sane veakneaa was noted in the miaala at the end of each one hour ezpoaure but thaj ware not in danger of eollapee* However, they weze Lass raalatant to the Tog duziag the eeeond weak and flee of the eight developed anifflaa. The lnflamateiy eendition did not reach the etage of bronchial relea. 6BRN002881 TOWOLDMONOOOI972 TIE TOX2CITT TIE THEHKAl rTCQKPOSITIOIf PMT '"S OF 'OS-951 Tel Monsanto Chemical Caqsuty, St* Louis, Missouri Xbunger Laboratories Certificate of Analysis - Pago 6 TABLE ZI EXPOSURE TO *06-95' XTST (HEA7T CCNCENTRATXCH) FOB FIFTEEN MINUTES At*rage Temperature Inoldo Chamber 76.5 F. Arerage Belstive Humidity Insida Chambsr 53*5 % Volatilisation Bata ............... ........................ .............. Supplnmntal Air Supply 10*4 IQ*/Boar (Rjuivalent To 14*5 Qb* /Boar) 3*5 Litora/Minute Starting Weipht Qi Weight After 2 W Animal Niaaber- Om. On* 1 2 3 4- 5* 6 7 8 225 no 240 235 250 220 225 235 IS 5 10 IS 10 25 20 15 Obearrutiona During Exposure Spensodic breathing pattern -- Copious salivation and nasal discharge -- Moderate laerimation -- Animals fairly steady, can be sen In front part of cage only. DISCUSSION All animals survived the fifteen almtea exposure to a heavy concentration of 05-95 decomposition prockicts. They aero lethargic and weak idiea restored from the chamber but were not In laaediate danger of collapse* Orel and nasal disoharge had a beat oeeeed vithin an hour* Moderate inflammation of the naeel mucoea was evident for tNenty>four to thirty-lx hours* The fog ess as danse ea eould be generated and was sufficient to obscure the animale excepting liien they ware in ths iasosdiate front station of the chamber* weight galas ran fron five to teenty-flva gzena two eeaka after exposure. SBRN002882 TOWOLDMONOOOI973 THE TOUCITT *' THF TTOOOl IBC^JKSITiai PiOT'Ts CP *08-95* Tot Monsanto Owalnal Company, St. Loola, Missouri lounger Laboratories Certificate of Analysis - Pag* f TABLE ZZZ Exposure TO *08-95' MIST (HEAVY CONCENTIUTiat) PGR ONE HOUR Q itnngi Temperature Inside (Sumter ....................... 78.0 P. inrag* Relative Hnnidity Inaid* Qwtar 52.0 % Volatilisation Rat*............... ............................... 10.1* XL. /Hour (Equivalent To li*.5 0a./8our) Supplemental Air Supply ....................... U.5 Litere/Minute Starting Weight Chang* m&k After 2 teaks Animal Waiter On. Oa. Obaarratlon* Etaring Exposure 235 10 Increasing lethargy -- 210 4 20 Alno*t no activity after 21*0 215 225 205 4 20 5 15 10 twenty mlnites -- Breathing reduced, teallow and irregular -- 230 5 Several laataneaa of gaaplng near 220 15 and of capons* -- Nasal and oral discharge -- Laarlnctlon. EISCDSSION - The one hoar exoomire to a heavy concentration of fog resulted in eollapa* for thro* of the anlnal* aid near eollapa* for the reminder. There were no deaths howvsr. Fairly rapid recovery waa noted after removal from the chaster. Bib ardmala *r* noving about In fifteen to fbrty-fiv* siaates although weak. 9*v*r*l day* w*r* re quired before activity and appetite retimed to noaul. Pulmonary congestion, insofar as oould be detemined by outward observation of breathing rata, had sub sided materially Is seven to tea days. ` All anlaale riiosod weight gains two weeks after treatment and it appeared that they would continue to thrive. GBRN0028B3 TOWOLDMONOOOI974 I THE TQUCITT ' THE THERMAL .TCPOS1TION PJCI^TTS CF '05-95* Tot Monsanto Chamlotl Company* St* Louis* Missouri Iranger laboratories Qartificate of Analysis - Pago 8 STNUHT OBOPP A EXPOSURE T*i MOEERATE ttST (Sg HOURS TOTAL) AH animals survived the schedule of six* one hair exposures spread ever a period of two weeks* Copious nasal discharge* salivation* lethargy* an) sodarate weak ness developed* The fog caused considerable inflanastien rad discomfort hut the eueuletlve effect was not lethal* ORQCP B EXPOSURE TO HEAVT COKCENTRATICS OF MIST (FIFTEEN MIHPTES TOTAL) So deaths resulted from fifteen alaxtes exposure to a heavy ecneentration of fog* there was irritation but the anlaals were not in danger of collapae* ffllOPP Cl EXPOSURE TO HFAVT COHCFirrRATIOK OP KI3T (CHE HOUR TOTAL) Collapse and near eollepaa developed in the latter stages of tbs one hair exposure. Bo deaths resulted* The anlaals were moving about In fifteen to forty-five minutes after exposure. Weakness was evident for several days* TOURER LABORATORIES Dsaiber 9th* 1958 Monsanto Project 758-1i6 The material in this report is to be used in development of the product sad may be given to responsible sales contacts, but it is not to be used by them in advertiiing copy. The oume of this material is not to be divulged until it appears in formal publications. No exceptions to the estab'ished rule may be made without the approval of the Medical Depart* meat ia St Louis.Customers' inquiries regarding matters of toxicity an to be referred as before to the Medical Depart* meat ia St Louie for reply. -- Monsanto Chemical Company GBRN00288H TOWOLDMONOOOI975 133 CLIFF CAVE ROAD Younger Laboratories St. Louis 39, Missouri BiockemiiU'... PUaAmacoloqi&U ... Attabf&U 1 Q&dijjiccde Analu&UPlONII TXZ.DBN 6*3 540 strajscT - Toxicological Investigation Of: Monsanto Sample Number 21 Monsanto Project Nusber T-6J-11 Pyranol 1470 March 4th, 1963 STTOT CCNDOCTD rOH Monsanto Chesical Company, St* Louis, Missouri SXPoRIMiOTAL PROCEDURE - A) Oral L03Q (Rats) The undiluted compound was rata. After the appro female rats we intervale at f ing data for c of the method e to oprague-Davley strain albino waj^determined, groups of male and at increments of 0.1 fractional log Lanket the toxicity range thereby supplyJ^o which was done according to a modification Observations were'Nmda--toxic symptoms and the viscera of the animals that succumbed were examined macroscopically* The data are shown in Table I* B) nkia Absorption MLB (Rabbits) The undiluted compound was applied in increasing dose3 at increments of 0.2 fractional log intervals to the closely clipped, intact skin of New Zealand white female rabbits. The treated areas were covered with plastic strips and the animals placed in wooden stocks for periods up to twenty-four hours, after which time they were assigned to individual cages. - Observations were made for toxic symptoms and the viscera of the animals that succumbed were examined macroseopieally. The data are shown in Table IX. GBRN002885 TOWOLDMONOOOI976 Tot Monsanto Cheaical jpaay it* Louis, Missouri Younger Laboratories Certificate of Analysis - Fag* 3 (3/4/63) " Y-63-II 50HMABI - (Continued) C) Skin Irritation (BabElla) Ths compound was classed as a aodsrata skin irritant. Tbs average aaxiaua score eas 4*6 out of a possible 8 in twenty-four hours. D) Eye Irritation (Babbits) The compound was classed as a soderate eye irritant. The average maximum score was 32.6 out of a possible 110 in one hour. 3) Vapor Inhalation (Bats) All anioals survived the six hour exposure as well as the following ten day observation period. It was concluded that the vapors were slightly toxic under conditions of the test. TGUNQSB LABORATORIES <>>L ' L/* BY: FRED M. YOUNGEB The material in this report is to be used in development of the product and may be given to responsible sake contacts, but it is not to be used by them in advertising copy. The source of this material is not to he divulged until it appears in formal publications. No exceptions to the established tula may be made without ha approval of the Medical Depart* ment in St Louis. Customers' nquiriee Mgardiag matters of toxiiitv are ti be referred cs before to the Medical Depart* ment in St. Louis for reply. -- Monsanto Chemical Company GBRN0D288& TOWOLDMONOOOI977 Tot Monsanto Chemical Company it. Louis. Missouri lounger Laboratories Certificate of Analysis - Page 2 (3/4/63) - 1-63-11 EXPERIMENTAL PROCEDURE - (Continued) C) Skin Irritation (Rabbits) the undiluted compound was applied to the clipped, intact skin of albino rabbits and removed after twenty-four hours. The application was covered with plsstic strips to retard evaporation. Observations were made over a period of several days for irritation. The data, scored according to the method of Draise, Woodard and Calvery (Journal of Pharm. and Exp. Therapeutics, Volume 82, December, 1944) are shown in Table III. D) Eye Irritation (Rabbits) C.l Milliliter of undiluted sample was placed in the conjunctival sac of the right eye of eich of three albino rabbits and observations osde over a period of several days for inflammation. The eyes were rinsed with warm isotonic saline solution after twenty-four hours. The data, scored according to the method of Draise, et al, are shown in Table IV. ) Vapor Inhalation (Hats) Four 150gram male rats were placed in a glass desiccator, 250 mm in diameter, and exposed for six hours to a concentrated atmosphere of vapors produced by passing a stream of air through 100 milliliters of the compound contained in a 250milliliter tall form gas washing bottle with fritted disc. Vapors from the bottle passed into a one liter bottle to remove droplets and then into the chamber. Air flow through the sample was 6 liters per minute as measured by a calibrated rotameter. This was sufficient to violently agitate the liquid. No supplementary air was introduced inasmuch as the above supply was ample for the animals oxygen requirements. The arHiMia were observed for behavior and, since there were no deaths, all were held for ten days observation. . The data are shown in Table V. 3UMMABT Pyranol 1470 A) Oral LD90 (Rats) The Oral LD90 for male and female rats was placed at- 2250 milligrams per kilogram with lower and upper limits of 1990 to 2553 milligrams per kilogram. The compound was classed as slightly toxic by oral ingestion in male and female rats. ' B) Skin Absorption MLD (Rabbits) The Minimum Lethal Dose by Skin Absorption in female rabbits was found to be greater than 2000 Milligrams par kilogram and less than 3160 milligrams per kilogram. Animal #3, dosed at 2000 milligrams per kilogram, very nearly succumbed. The compound was classed as slightly toxic by skin absorption in fsmala rabbits. GBRN002887 TOWOLDMONOOOI978 To: Monsanto Chemical L. -pany St. Louis, Missouri lounger Laboratories Certificate of Analysis - Page 4 (3/A/63) - T-63-U __ T A B L 1 ras CRAL LD 90 OF 'Pyranol 1470' FOR RATS Sample Fed Undiluted Animal Mo* - Sex .'eight 0 n. 1- Female 2- Female 3- Male 4- Male 5- Female 6- Female 7- Male 8- Male 9- Female 10- Female 11- Male 12- Male 13- Female 14- Female 13" Male l6- Male 17- Female 16- Female 19- Male 20- Male 225 210 2 35 250 215 220 240 245 230 215 . 235 240 220 210 235 225 220 215 235 245 Dose 1580 1580 1580 1580 1580 2000 200C 2000 2000 2000 2510 2510 2510 2510 2510 3160 3l60 3160 3160 3160 Fate Survived Survived Survived Survived Survived Survived Survived Survived Died Survived Died Survived Died Died Died Died Died Died Died Died DISCUSSION - The Oral LDJ0 for male and female rats was placed at 2230 milligrams per kilogram with lower and upper limits of 1990 to 2355 milligrams per kilogram* The compound warn classed as slightly toxic by oral ingestion in sale and female rata. Survival time was approximately twenty-four hours to three days with most deaths occurring in two to three days* Toxic symptoms included increasing weakness, severe diarrhea, tremors, and collapse* At autopsy there was inflammation of the gastric mucosa, liver discoloration, and renal hyperemia maeroseopically* GBRN002888 TOWOLDMONOOOI979  Tot Monsanto Chemical Coar-ny it. Louis, Missouri Younger Laboratories Certificate of Analysis - Fag# 5 (5/4/63) - Y-63-11 T A 3 L II THI MINIMUM LiTHAL SQS OF 'Fyraaol 1470* BY SKIM ABSORPTION IN RABBITS Sample Applied Undiluted Animal No. -_3ex 1 - Female 2 - Feaale 3 - Female 4 - Female 5 - Feaale 6 - Female eight JL*i- 2.5 2.2 2.3 . 2.6 2.5 2.5 Oose 794 1260 20C0 3160 5010 7940 1iii i4^*iiii I /eight Change 5 Days Later - 0.1 - 0.1 - 0.2 - 0.3 - 0.2 - 0.4 ___ Fate ______ Survived Survived Survived Sled - 10 Days Oied - 7 Cays Sled - 7 Oays JlSOCSSICN The Minimum Lethal Cose by olein Absorption in female rabbits was found to be greater than 20C0 milligrams per tcilogram and less than 3160 milligrams per Kilogram. Animal *?3 dosed at 2000 milligrams per kilogram, very nearly succumbed. The compound was classed as slightly toxic by skin absorption in feaale rabbits. Survival time wsb seven to ten days. . Toxic symptoms included loss of appetite, lethargy, and increasing weakness. .eight losses ran to forty per cent of starting weight. At autopsy there was liver discoloration and renal hyperemia macroscopically. GBRN0028B9 TOWOLDMONOOOI980 Tot Monsanto Chemical Company 3t. Louis, Missouri Younger Laboratories Certificate of Analysis - Page 6 (J/4/6}) - Y-65-11 _ T A B L S III LKIN IBBITAIIQN IN BABBITS AFTLB APPLICATION OF 'Fyranol 1470' Sample Applied Undiluted Animal Number Nuaerieal ^Valuation At The 2nd Of l_gour 24 Hours 48 Hours 72 Hours 1?C Hours l68_Hours 1 3 5 '4 3 2 1 2 24 3 2 1 0 3 35 4 ? 2 1 Average 2.6 4*6 3.6 2.3 1.6 0.6 0I5CUSSICN - The compound was classed as a moderate skin irritant* The average maximum score was 4*6 out of a possible 8 in twenty-four hours* ell-defined redness with very slight edema developed within an hour for an average score of 2.6 out of a possible 8* Overnight taere was well-defined to moderate erythema and slight edema increasing the average score to 4*8. No blistering was observed. Inflammation gradually receded following removal of the application. After seven days one animal was given a score of zero but very slight redness was still present on the remaining animals* GBRN0O2B90 TOWOLDMONOOOI981 Tot Monsanto Chemical o.apaay >>t. Leal*, Missouri Younger Laboratories Certifies!* of Anslysls - Pag* 7 (3/V65) - T-6>11 -- T A a L i IV ITS IHiilTATICH ZN RABBITS AITIH APPLICATZCN 07 '.yranol 1470* lespl* (0.1 MHUlitor) Applied Undiluted Aninal Nunber Numerical Evaluation At 7b* End Of 1 Hour 24 Hours 48 Hour* _ 72 Hour* 120 Hours 168 Hours 1 33 26 17 12 6 0 2 28 21 13 a 4 c 3 53 30 2C 12 6 0 Avenge 32.6 O* 6 16.6 10.6 5.3 0*0 jIICUSOICN - - The cospouad aa claseed as a soderat* eye irritant. The average **-- acor* mi }2 6 out of a possible 110 la on* hour. 7h*r* >*s int*raitt*at raving at th* jr*a for several aimites following application. After on* hour th* average ocor* ma J2.6 out of a poaalbl* 110. alight *d*aa, alight to eoderate redness of th* eosjunetiTae, copious discharge, ind slight iris congestion d*v*lop*d. Th* oomeal area cleared soaeehst in twenty four hours and elthln fir* days iris and cornea were normal. Conjunctivitis and edesn cleared completely ithla seven days. GBRN002891 TOWOLDMONOOOI982 To: Monsanto Cheadeal v ,paay St. Louis, Missouri 'lounger Laboratories Certificate of Analysis - Pag# 8 (3/4/63) - 1-63-11 TABLE V INHALATION OT 'Pyranol 1470' VAPORS BT BATS Anns* Temperature Insids Chamber ..................................................... Average Relative Huaidlty Insids Chamber............................ ............ 73* y. 42 % Aniaal No. - San Tats 1 - Male 2 - Male 3 - Hals 4 - Hals Survived Survived Survived Survived Obssrrations During -Exposure Occasional pawing at tbs syss in ten to fifteen siaatea ... Slight nasal disehargs ... Sons discomfort ... No real weakness ... Occasional irregular breathing. DISCUSSION - All animals survived the six hour exposure as well as the following ten day observation period. It was concluded that the vapors were slightly toxie under conditions of the test. The vapors produced mild nasal and eye inflammation as sell as some discomfort. No weakness of consequence was noted at the end of exposure and no bronchial rales developed. Activity and appetite returned to normal within twenty-four hours. Nasal inflammation disappeared within seventy-two hours. No respiratory complications developed during the ten day observation period. GBRN002B92 TOWOLDMONOOOI983 PROJECT NO; ;ip:rt file Younger Laboratories BiooUtmliU ... PUaimac&l&fiiU ... /^HahfiU OfLZL&ZLPkU 198 CLIFF CAVE ROAD St. Louis 99. Missouri - PSONII TILS BN 6*9 S AO Gefitifacate AnaLfUi Deesofter im. 1963 mnct - fSKLMlSglttl IxreetLgatloa Ofi Moasaate Saaple luefeer 112 Project Mir HCS - 900 ttTOT ooraczB rot lie Ctalnl , It. Leals, Klssourl BJ>SXX*IAL PJDCS>0BS - A) Oral LD,o (bits, Nixed See) tbs SBdilsied eoepeusd ale aad feasle te iprsgue-Dawley strals albino After the ap; feasle rats ixtsrosls at lag dsts ter sf tbs BStbod s KS deteraiaed, groups of eels sad at laeresasts ef 0.1 fretocsl leg si tbs tealsltjr nags tbersb7 supplpdeas aeeerdlsg te s Rsdifiestlaa Observations ei tezls spaptens sad eeeepieallp. viscera ef tbs salsals tbst Tbs dsts sre is teble I. ) fids Absetpilea NLD (babbits, Nixed lex) tbs aadllated ooapoand ass applied U laereesiag dsess st issressats of 0.2 frostiossl leg ixtareuls te tbs eleaelp slipped, lxtsst ekia ef lee Zeslsad eblte asle sad feasle rabbits. tbs treated areas ewe covered eith pisstie stripe sad tbs ssiasls placed is eeedes steaks ter perleds up te teestp-four beers, after ebieb Use tbsp ears aaaigaed te individual sages. Obsereutless ears aado ter tosie apeptcaa aad tbs viscera ef tbs sxiasls that suesuabed ears ms) aed aaeroaeopieallp. tbs data are shew lx table IX. ' GBRN002893 TOWOLDMONOOOI984 tei NuMBte Chaaleal tpaap St. Louis, Missouri louagr Labor*toriee CertifLeat* of Aaalpsis - Page 2 (12/19/6}) - 7-65-86 XXP^glMOITAL F10CH>U1 - (Coatlnued) - C) AH lrrltatloa (kMlto) Ott aadllated ccapoaad mi applied to too flipped, lataet tola of alblao rabbit* ad reaoved after tseatp-feur hear*. The applleatlea aaa covered oito plaetle trips to retard evaporatlaa aad avoid eeataaiaatioa. Observations sere Bade ever a period of several daps for lrrltatloa. the data, seared aceardiag to toe Method of Dralse, beodard aad Calvery (Journal of Fharo. aad bp. therapeutics, Velaae >2, Deeoober, 1944) are toesa la table III. D) Spe lrrltatloa (Babbits) 0.1 Milliliter of sadllsted asaple sas placed la toe eoajuaetival aae of the right epe of eaeh of three alblao rabbits aad observatioas sad* ever a period of several daps for laflaitloa. the epee vere riased vlth aua laoteaie aallae aolatlea after tsaatpfour hoars. The data, soared aeeerdlaf to the Method of Oralse, et al, are toesa la Table XT. a) Vapor lahalatioa (Male Bata) TOar 150-grea sale rats sere placed la a glaas desleeator, 250 ms la dieaeter, aad sspesed for six hours to a eoaetotratod ataospharc ef tapers produced bp pssst ag a streaa ef air through 150 allliliters of the eeaposad eeatalaed la a 250-allllllter tall fen gaa saahlag bottle alto fritted dise. Vapors frea the bottle passed late a eae liter bottle to rcaove droplets aad thca iato the ehaaber. Air flee threap the saaple saa 6 liters per alaate aa Measured bp a calibrated rotaaeter. this sas suffleieat to vleleatlp agitate the liquid. Mo supplesaatarp air aaa latrodaeed laaasueh as toe above supplp sas aaple for tbs astasia oxpgfH roquireacats. The vere observed for behavior aad, siaee there sere ao deaths, all sere bold for tea dape ebservatioa. the data are toesa la table T. smui! - MCI-500 A) Oral LD>0 (Bats, Mixed Sex) the Oral U)99 for aale aad foaale rats saa placed at 6,920 aUligraaa per kilograa with lever sad upper lialts ef 7,045 to 11,325 aiUlgraas per kilograa. the eospeuad sas classed as praetleallp aoa-tsxle bp oral iagestloa la aale aad feaale rata. B) Skis Absorptlaa KLD (Babbits, Mixed icx) the Mini aaa Lethal Dose bp 5kla Abserptloa la aale aad feaale rabbits ae feaad to be greater than 5960 allligraMs per kllegraa aad less than 6310 allllgraas per kilograa. The eoapouad sas classed aa allghtlp toxle bp skla absorptlaa la aale aad feaale rabbits. GBRN002B94 TOWOLDMONOOOI985 fv HoMMte CWslsal .jmjmaj At. Lull, KiMovri Teuagar Labor*Wrlee Csrtifluts sf Aanlyvia . Ft( 5 (12/19/631 - T-63-M SOHKABI - (Csitl--4) C) Akia Irritatic* (labtlM) & eawpoaad ni 1uh4 as a wtint* akia Irritant vbaa sppllsd undllutad to lataat nkkit Aim. & trin| ill-- war* m* 4*5 t af a paaalfcla la tvantp-fear Wars. 9) Ira ZrritatiM (MWita) Ika aaapoaai m alaaaaA aa a alii agr* irritaat. Bia average aariaaa aaara aaa 1M aat af a pasalbla 110 la aaa War. X) Vapar lahalatiaa (Halo Bata) All aaiaala aanrlvaA Um ala War aspaaara aa wall aa tha fallaaiw taa dap Warvatloa parted. Zt aaa aaaaladad that tha ropers vara prastlsallp aoe-tazia aadar aoaditioaa af tha taat* I0DBBXB U90XAT0IIES kkr 1 /h~Ul ait rxis The material in this report is to be used in development' the product and may be given to responsible sales contact., but it is not to be used by them in advertising copy. The source of this material is not to br> divulged until it appears in forms1 publications. No e::o'.;'.tiau3 to 1 ha established rule may be made without the rjTcrj-al cf the Medical Depart ment in St. Louie. Cuotorne*r.' inooi .-ion receding matters of toxicity are to be rjfer.rd 83 be'.bra to the M edical Depart ment in Sl Louis for reply. -- Monsanto Chemical Company 6BRN002895 TOWOLDMONOOOI986 fat bMuto Cfcesleal wjjiv it. Louie, Missouri Toaster Laboratories Certificate of Aaalysls - Fi| 4 (12/19/43) - 1-43-68 TAIL* Z TKS OBAL LD,C Of 'MCI-30O' TDK BATS teapl M Sadilated *"<--i a. - Sax Vatgbt ,ia 1- resale 2- ramie y Mala 4- Male 9" resale 4- resale 7- Male ft- Male 9- resale 10- resale 11- Male 12- Male 13- ramie 14- resale 13- Male 16- Male 17- resale 1ft- resale 19- Male 20- Male 220 233 230 240 240 225 245 250 215 220 230 235 205 215 235 240 220 225 235 240 Base M*./i. 4.310 4,310 4,310 4,310 4,310 7,940 7,940 7,940 7,940 7,940 10,000 10,000 10,000 10,000 10,000 12,400 12,400 12,400 12,400 12,400 fate arrived arrived arrived filed arrived arrived Died filed arrived arrived filed filed arrived arrived filed Died arrived Died filed filed DI5CTSSICB - The Oral 1D,0 Male aad fseals rats ms placed at *,920 nilraaa psr illacres with loasr ui apper lints of 7.043 U 11,323 Mllllfrass par kilsgraa. As eeepsaad ms slssssd as preetleally bob-taxis by sral laceetia* la sola u4 fsaale rats. arrival aa tao to six days alth mat dsaths saaarrlaf la tm s three days. Axle eyaptoea iaeludad severe diarrhea, loos sf appetite, lacroaslac seakness sad sollapsa. At aatepoy tiara eas isfls-- ties sf tbs gastrelatestlasl meosa alth liver sad raaal kyperesla. GBRNQ0289 6 TOWOLDMONOOOI987 hi Naaaaato CtahU C--paay *t. iouia, Idaaearl Toaster Laboratories Certificate of Aaalyaia - Pt(i 5 (12/19/63) - T>6>-08 TAILS ZZ ns NUZKSX LETHAL DOES Of HCft-jOC >1 SKIM ABSOSPfZO* 1* 1A1BXTS pi* Appliai Va411ata4 Aal--1 Re. - Aaa eight Oaaa eight Chaage } Saps Later s*. 1 - faMia 2 - Mala 9 - faaala 4 - Bala 5 - faaala 6 - Mala 2.2 1,000 2.5 1,J0 2.2 2,310 2.4 3.9*0 2.3 *.310 2.6 10,000 0.0 - 0.2 - 0.2 - 0.4 - 0.3 -- rata AarrleoA AarrlvaA tarried tarried 0la4 -- 3 Days 01*4 -- 9 Oaya DUCTSaiCI - ft* Mil-- Lethal Dwt by >>kii Absorption la aala ul fault rabbits aaa food to ba greater tfaaa 5960 ailll*raaa par kllagraa aaA laaa Uu 6310 Bllllgraaa par kHagras. ha iwytwi m alaaieA aa allghtly tad* hj akli buryttw la hit aaA faaale rabbit*. ^arrival tlaa aaa tkraa to fire 4apa. Tad* ayaptoaa lacld*4 aaa1maaa, traaora, ad aaaalar lapalraaat aftar forty*eight ta aareaty-taa baara. At aatapay a* vlaaeral abaago* af aaaaaqaaaaa ara aet*4, asaaptlaf far palaaaary GBRNQ02897 TOWOLDMONOOOI988 Tsi Monsanto Chssical Cespaap at. Louie, Hlssesrl Younger Laboratories Certificate of Analysis - Pag* 6 (12/19/6}} - T-6>*W TAILS ZZZ ttZX ZI8IIAT10N ZS RABBITS ARSB APPLICATION Of *NCS- 50 0' Sasple Applied Badilated Aalsal Nnaber Nuserleal fvalaatioa At The Bad Of 1 Bear 14 feari 4B Hear* 72 lour* 120 lour* 1<8 lours 1 2 3 Aveng* 04 4 3 2 1 03 4 3 3 2 04 3 3 2 2 0.0 4.3 3.4 3.0 2.4 1.4 DISCUSSION - Dm eospound saa classed aa a Moderate Ala Irritant shea applied undiluted to Intact rabbit akin. Tki average sari sun score van 4.5 out ef a possible in tesntp-four hours. He akin changes vers noted after one hour. Overnight there ess sell-defined erpthesa sith alight to nodcrate sdeoa for an average score of 4*3* No blistering developed but the edges of the treated areas sere outlined bp definite raising. Reduction of iaflaasatloa saa gradual fOlloslBg resoval of the application. After seven daps alight redness and availing sore still present. GBRN002898 TOWOLDMONOOOI989 To Moaaaato Cboaloal mpaiy St. Louia, Kiaaourl Youayor Labor*torio* Cortifloat# of Aaaljslo - fay# ^ 112/19/6}) Z-6>>BS I1IL1 XV as lumnoi is unin srtsi applxcatxos or hcb-joc1 Saaplo (0.1 Nlllllltor) Appliad ladllato* Aalaal Baabor Bnaorital Brain*tlon At 7b* Bad Of 1 Boar 24 loaro 46 loaro 72 loaro j2Q_loaro 146 lour* 1 2 9 Avoray* It 14 11 7 2 0 IB 19 94 0 0 2} IB 19 9 4 0 19.4 15.4 11.0 6.6 2.0 0.0 DLSCUSSIOH - 7b* ooapoaad nao olaaood aa a alii oy# lrrltaat. th* ayoray# --niaaa ooer* nao 19>( oat of a poaalbl* 110 la mo boar. Diaooafort aaa aadorat* laaodl *tly f#U#t*y applioatiaa. Mild rodaoo* of tb* totjuitlno, allybt odoaa, llttlo or a* dlaobaryo, aad allybt ooraoal dallaoao dorolopod altbla oa* boar for aa utr>< aoor* of 19.4. Coayootiaa Aocroaaod allfbtlr 1* to#otyfoar hour*. Za fir* days, irlo aad . .ooraoa oar* oloar aad only a trao* of oryth--a raaalaod for aa avarayo aoor* of 2 0 GBRN002899 TOWOLDMONOOOI990 ta Monsanto Gheaical Cwspaay St. Louis, Missouri Younger Laboratories Certificate of Analysis - p*g* a (12*19-6}) - Y-65-SS TA B L I V XNBALATZCII 07 'MCA - }00' VAPOBS BY BATS Average Temperature ZaiUl Ckubtr ................. ................................... .. Arwifi lilatln Bualdlty Xaaid* Chaaber ........................................... Aaouat Of Saapla -- To Start............. .. 150 *0 Baoovarod......................145 m Vaporised or loft 1a tha apparatus........... 2 e (1.556 ) 77* p. 49 % Aalaal Bo. - Sox 70to 1 - Halo 2 - Mala 5 - Mala 4 - Mala Survived Survived Survived Survived Observations Parian topoeure Mild lethargy aftor thirty to sixty alaatos ... Bo discomfort ... anal breathing rata ... Bo Inflaaaatloa. B1SCBSSZ0I - All aalaala survived tha six hour exposure as call as the following tea day obsanratloa period. Zt aaa aoaeladad tnat tha vapors vara practically aea-texie u^er aoaditloaa of tha tost. Tha aalaala appeared to be uaaffactad by the exposure. Bo signs of irritation or discoafort aero aotad during tha test. Basal and ocular ausosac sera free of inflaaaatloa upoa exaadaatioa at the aad of tha six hours. The tea days observation period ess aasvsatful. GBRN002900 TOWOLDMONOOOI991 Younger Laboratories BiocUemUU ... PinvunacolofUU ... AnalyiU 1SS CLIFF CAVE ROAD Saint Louis. Mo, 63139 PlONIi TILD1N 6*3860 SUBJECT Tsxieelsgieal Investigation Of: HCS - 404 Monsanto Saaple luaber 245 Monauto Project Rubtr 1-65-214 January 12th, 1966 STUDY CONDUCT FOB Monsanto Ceapany, St* Louis, Missouri EXPERIMENTAL PBOCBUBI - A) Oral LD,0 (Bats, Mixed Sox) Tho undiluted cospound sss fod by stoaach tubs to Sprague-Davley strain albino nalo and feaale rats* Aftor tho approziaato Hiaiaua Lethal Doss saa determined, groups of aals and finals rats sort fad in increasing doses at ineraasnts of 0*1 fraetioaal log intervals at four levels designed to blanket the toxicity range thereby supplying data for calculation of the LD,0 which was dons according to a codification of the aethod of S* J* do Beer* Observations were aade for toxic synptoas and the viscera of the salsaIs that suecuabed were exaaiaed aacroesopically* The data are shows in Table I* B) Oral MLD (Babbits, Mixed Sax) Tho undiluted coapound was fod in increasing doses at iaereaents of 0*2 fraetioaal log intervals by stoaseh tube to Hew Zealand white aale and feaale rabbits* Observations were aade for toxic syaptoas and the viscera of the aniaals that suecuabed were exaaiaed aaeroseopically* The data are shown in Table II* 6BRN002901 TUt wfid--rilwpor> bM t* bt wdh si faf-- d ad--nMaf db TOWOLDMONOOOI992 To: Monsanto Company St* Lauia, Missouri younger Laboratories Certificate of Analysis - Page 2 (1/12/66) - 1-6^-214 DCPERINOfTAL PBOCBOBX - (Continued) C) Skin Absorption HLD (Babbits, Nixed Sax) The undiluted eoupeund uas applied in increasing doses at inereaents of 0*2 fractional leg intermix to the closely clipped, intact skin of Hew Zealand shite sale and feaale rabbits* The treated areas were cowered with plastic strips and the aniaals placed in wooden stocks for periods up to twenty-four hours, after which tiae they were assigned to individual cages* Observations were aade for toxic syaptoas and the wiscera of the aw-i--that sueeuabed were exaained aaeroscopically. The data are shewn in Table III* D) Skin Irritation (Babbits, Mixed Sex) The undiluted coapeund was applied to the clipped, intact akin of aale and ' feaale albino rabbits and reaowed after twenty-four hours* The application was cowered with plastic strips to retard evaporation and avoid contaaiaatioa* ' Observations were aade over a period of several days for irritation* The data, scored according to the aethod of Draise, Voodard and Calvary (journal of Pham* and Xxp* Therapeutics, Yelume 82, Deeeaber, 1944) ere shewn in Table IT* X) Bye Irritation (Babbits, Mixed Sex) 0*1 Milliliter of undiluted saaple was plaeed in the conjunctival see of the right eye of each of three albino rabbits and observations aade ever a period of several days for inflsaaation* The eyes were rinsed with warn isotonic saline solution after twentjrfeur hours* The data, scored according to the aethod of Draise, et al, are shewn in Table Y* Y) Taper Inhalation (Male Bats) Tour nature sale rats were placed in a aetal chamber of 55 liters capacity and exposed for six hours to s concentrated atnosphere of vapors produced by passing a streaa of air through 100 ailliliters of the eoapeund contained in a 300-milliliter Xrlenneyer flask. Yapors from the flaak passed into a one liter bottle to remove droplets and then into the ehanber* Air flew through the sanplo was five liters per ninute as neasured by a cali brated rotaaeter* This was sufficient to violently agitate the liquid* Ho supplaaeatary air was introduced inasmch as the above supply was ample for the aniaals oxygen requireaents* The aniaals were observed for behavior and, since there were no deaths, all were held for tea days ebservatioa* The data are shown in Table YI* GBRN002902 TOWOLDMONOOOI993 To: Monsanto Ceapany St. Louis, Missouri Younger Laborstoriss Certificate of Analysis - Page 3 (1/12/66) - 7-63-214 SUMMARY - A) Oral D,0 (Bats, Mixed Sax) Tbs Oral U>.0 for aalo and fsaala rats sas placed at 19,800 ailllgraas par kilagraa with lever and upper Halts ef 17*030 to 23,16$ ailligraas per kilagraa* Tbs eoapeuad sas classed as practically aoa-toxic by oral ingestioa in sale aad feaale rats* B) Oral MLD (Babbits, Mixed Bex) The Minivan Lethal Oral Deae for sale and feaale rabbits was found to be greater than 1580 ailligraas par kilagraa aad less tfaaa 2510 ailligraas per kilagraa* ' The ceapousd sas classed as slightly toxic by oral iagestioa in sale aad feaale rabbits. C) Skis Abaorptioa MU) (Babbits, Mixed Sex) Bw Miaiaua Lethal Beal by Skin Absorptive la aale aad feaale rabbits sas found to be greater thaa 1000 ailligraas per kilegrsa aad less than 1580 ailligraas per kilagraa* The eoapeuad sas classed as aildly toxic by akin abaorptioa in aale aad feaale rabbits. D) Skin Irritation (Babbits, Nixed Sex) The eoapouad saa elasoed as a alight akin irritaat shea applied undiluted to intact akin ef aale aad feaale rabbits. The average aaliana score sas 0*6 out of a possible 8 in twentyfour hours. X) Xye Irritation (Babbits, Mixed Sex) The eoapeuad sas classed as a slight eye irritant in aale and feaale rabbits* The average aaxiaua score was 11*6 out of a possible 110 in one hour. T) Vapor Inhalation (Male Bata) All aaiaals survived the six hour exposure as veil as the following tea day observation period* It was concluded that the vapors were relatively non-toxic under conditions ef the test. YOOMSER ULBOSATOSIXS "Jr BY: TEED M YOUMGKB 6BRN002903 TOWOLDMONOOOI994 Tet Monsanto Ceapany St. Louis, Missouri ,, louder Laboratories Csrtifiests of Analysis - Page 4 (1/12/66) - 1-65-214 I 11 L I I THE OBAL LD)0 QT 'KCS- 404' YDS BATS Saapls Pad Undiluted Aniasl No. - gas Vsight SB . 1- fsaals 2- Rais 3- fsaals 4- Hals 9- fsaals 4- Rais 7- fsaals 8- Hals 9* fsaals 10- Hals 11- fsaals 12- Hals 13- fsaals 14- Hals 15- fsaals 16- Hals 17- fsaals 18- Hals 19- fsaals 20- Hals 230 245 220 240 225 250 235 260 240 265 235 255 225 250 230 270 235 255 240 260 Doss gf-Zli 12,600 12,600 12,600 12,600 12,600 15,800 15,800 15,800 15,800 15,800 20,000 20,000 20,000 20,000 20,000 25,100 25,100 25,100 25,100 25,100 fats Survived Survived Survived Survived Survived Survived Survived Survived Died Survived Died Survived Died Died Survived Died Died Survived Died Died DISCUSSION - Ths Oral LD.a for aals and fsaals rats was placed at 19,800 ailligraas par kilograa with lever and uppsr liaita of 17,030 to 23,165 ailligraas par kilsgrua. Ths eoapoaad *as elasssd as praetieally son-toxic by oral iagsstioa ia aals and fsaals rats. Survival tins sas several boors to four days with aost dsaths oseurriag ia thrso to four days. Toxio syaptoas iaeluded severs diarrhsa, loss of appstits, and iaersasing weakness At autopsy ths gaatrsintsstiaal tract mm gassous and thsrs sas liver congestion. * BBRN002904 TOWOLDMONOOOI995 Tot Monsanto Company St. Louis, Missouri lounger Laboratories Certificate of Analysis - Pag* 5 (Vl2/o6) - >65-214 TABLE XI THE MINIMUM LETHAL ORAL DOSE OF *MCS- 404' FOR RABBITS Staple Fed Undiluted 1 - Female 2 - Male 3 " Female 4 ~ MSle 5 - Female 6 - Male eight .51:. 2.3 2.4 2.6 3.1 2.7 2.7 Dose Mf*/_Kfc 1000 1580 2510 2510 3980 6310 Weight Change 5 Days Later Kg. 0*2 0.1 - 0.2 - 0.3 - 0.2 - 0*3 Fate Survived Survived Died -- 5 Days Diad -- 7 Days Died -- 8 Days Died ~ 8 Days DISCUSSION - The Minimis Lethal Oral Dose for aale and female rabbits sas found to be greater than 1380 ailligraas per kilogras and less than 2310 milligrams per kilogram. The compound was classed as slightly toxic by oral ingestion la aale and female rabbits. SurriTal time was fire to eight days. Toxic symptoms included gradual loss of sppetite with increasing weakness, lethargy, and collapse* At autopsy there was renal, liver, and pulmonary hypereaia by macroscopic examination. The irct-rial in this report is to H u- in daveiepment of tbs product t-.d ru-.j ha \.ivs n .o rcov : '3 las t rr.ia.rte, V.z i: i.i to be ' t' ' ` cv ". n.'9 p--. :s l t.i: i i". 1` : ' ' io i;:: "-1: l:;?; ' . ; ` icr.:... 1 '> ' t. ' ' . ' ' ` ' - y.r' il `. 1 ' j '5v.:-l I'. ie ; 1 Ti - 1 i'f toxiri.y Lf- tJ f.i i'.'. i-J - -J nent in St. Lout3 tot tsp.y. --. Monsanto Clismicnl Ccmpnny GBRN002905 TOWOLDMONOOOI996 to: Monsanto Cospany St* Louis, Missouri lounger Laboratories certificate of Analysis - Page 6 (1/12/66) - -65-214 TABLE III ZEE MINIMUM LETHAL DOSE ON 'MGS- 404' BT SUN ABSOHPUCM IN BABBITS Saapls Applied Undiluted Aniaal No* - Sex 1 - resale 2 - Male 3 - resale 4 - Male 5 - resale 6 - Male Veight JJU. 2.7 3*3 2.5 2.6 2.3 2.8 Dose UzJStz 631 1000 1500 2510 3900 6310 eight Change 5 Days Later _____ Ui_____ 0*1 - 0*1 - 0.2 - 0.4 - 0*2 - 0.3 ______ Nate________ Survived Survived Died -- 6 Days Died -- 9 Days Died - 14 Days . Died -- 5 Days DISCUSSION - Tbs Minima Lethal Dose by Skin Absorption in aale and feaale rabbits was found to be greater than 1000 ailligraas per kilograa and less than 1500 ailligraas per kilegraa* The eoapound eas classed as aildly tozio by skin absorption in sale and faaale rabbits. Survival tine eas five to fourteen days* Toxic syaptoas included weakness after three to six days, reduced appetite, dyspnea, collapse, and paralysis* At autopsy there was pulmonary hypereaia} otherwise no visceral changes of consequence were noted. GBRN002906 TOWOLDMONOOOI997 To: Monsanto Company St* Louis, Missouri Tounger Laborstoriss Certificate of Analysis - Page 7 (1/12/66) - f-65-214 T A B L X 17 SKZX ZBBItATIOH IN BABBITS A7TXB APPLICATICH OF 'HCS- 404' Saaple Applied Undiluted Anlaal Mo*- Sax Muaerical Xvaluatioa At She Bid Of klSST 2$m Hours 4_fours 72 Hours l2g_fours 1 - Male 2 - Feaale 3 - Hale Arerage 01 1 0 00 0 0 01 0 0 0*0 0*6 o*3 0*0 0 0 0 0*0 Discussion - The coapeuad saa classed as a alight akin irritant when applied undiluted to intact akin ef sale and feaale rabbita. The average asrlaua aeore ess 0*6 out ef a possible 8 ia twenty-four hours* Mo akin chaagea were noted at the end of one hour* Overnight there were two instaneea of very alight redness with ae edeaa for an average aeore of 0*6. Within seventy-two hours all aaianla were free of inflaaaatioa* - BBRN002907 TOWOLDMONOOOI998 To: Monsanto Company St* Louis, Missouri Tonager Laboratories Certificate of Analysis - page 8 (1/12/66) - y-65-214 TABLZ T m IKEITATIGR IH BABBITS ATTEB APPLICATIOH OF 'MCS- 404' Ssapls (0*1 Killllltsr) Applied Undiluted .aal Bo* - Sex Runerieal evaluation At She bd Of 1 Bour 24 Hours 4&. gpars 72_lours 120 Houi 1 - resale 11 9 4 2 2 - Male 11 6 2 0 3 " resale 13 a 4 4 0 0 0 Average 11.6 7*6 3*3 2*0 0*0 BISCtrSSIOH Ths conpeuad as olasssd as a alight ays irritant* The average sarisun seors sas 11*6 out of a psssibls 110 in ons hour* Thera sas blinking but no pawing at ths ayes foilswing application* Mild discharge, slight redness, very slight edaaa, and alight corneal dullness was recorded after one hour* liana and discharge disappeared overnight* Uthia three days only a trace to slight erythana resained on two aniaals. GBRNQ029Q8 TOWOLDMONOOOI999 To: Monsanto Ceapany St. Louis. Missouri Younger Laborstorios Certificate of Analysis - Pago 9 (1/12/66) - 1-65-214 T A B L * TI HTHAIATIOR Of* 'NC8- 404' TAPQRS BT IAS Average Toaporatnrs Inside Chasbor.......................................................... 74* p. Average flelative fluidity Inside Chasbor ............ .............................. .. 44 % Aaeunt of Sasplo -- To start.............................. Becovered *........................... Vaporised or loft is equipment...................... 100*0 os 99*5 os 0*5 oe (0*5%) Asisal Mo._-Sox 1 - Halo 2 - Mala 3 - Mala 4 - Halo ____JUt#___ _ Sarvivod Survived Survived Sarvivod _ Observations Daring pcposuro Mo iuodiato offoat ... Lethargy after oaa hoar Mo diseonfort ... Normal respiration MO vaakness. DISCUSSIOM - All asisala sarvivod the six hoar exposure as veil as the folleoiag tan day observation period* It vns concluded that the vapors were relatively ao^taxie under conditions of the test. V&ih the exception of sodorate lethargy, the anlsals shoved no reaction to the vapors* Weakness ass absent and no nasal or ocular infl aasatloa ass noted. Aativity and appearance acre nornal the day folloving expocur* and as respiratory coaplieatiou developed daring the tan day observation period. 6BRN00290? TOWOLDMONOOO2OOO TOWOLDMONOOQ2001 Jji XoAuats JliMtcil rflfujr it. Missouri TM(r jMittwlti lertifieate Aavl/sis - rag" `/6A, - .'-t- BPBOUarrAL FMCAOU - (CoatiMed; C) Skis Absorption KU> (tobbita, Mixed m) Tke undiluted eo;ouad aaa applied ia .nereaan.- .:.** at i:.cre*nt< ... fraction*! log interval.* to tbo tlooeiy eloped, i .t .et :*u .f ** ,,-*.r.d bite sale aad feaal* rabbit*. Til* treated arev* vere covered eitn plastic strips i the miaals pieced 1voed stocks for periods up to teeaty-fowr hours, after emcb ttse they were assigned to indlrilual cages. Observations sere aad* for toxic syvptoos tnd the rue era .f me asisale that suecue* ed eere exsaiaed *nc".*co;ic illy. The data are sheen la Table III. D) Ski* Irritation (Saboit*; Ik* undiluted cos; ouad as* applied to tne clipped, int.ct .in of <lbiao rabbits tad moored after teeaty-four boura. Tb* epplicatioa eae covered with plastic atrip* to retard evaporation aad avoid cent valuation. Observations vvrv aad over a oeriod cf several :*ye for irritation. Tie data, scored according to thr letbod of .mae, eoodtrd and Talvery :Journal of rhar*. aad cp. AarapeuticF, /oluae oi, Teceuter, lj41 are aeoaa in Table IV. S) ^r# Irritation (babbits; 0.1 Milliliter -f uadilutad snusple eaa placed ia the conjunctival sac of the right eye of mc: of tore* <lbiao merits aad observed on* sad# over a period of several daya for infla**atioa. The eye* ware rinsed with ears isotonic saline solution after twenty-four aoure. Ike lata, scored according to t.te aetaod of Trait*, et ail, are ano*a ia Table V. f) Vapor lahalatioa (Mala Rata) four 150*gr*a aale rata sera placed ia i glass desiccator, vc < in :taater, and exposed for 6 boura to i coac eat rated ataoepbere of vapors produced by passing a straaa of air taroucS 1~0 aillKiters of the co*pound cootalaed ia a ;^wihiit.r t;i for* gas aa.-Ju.ag bottle nb fritted disc. Vapors fro* the bottle passed into a one liter oottie to rvc*- imp let* and tnen mtc to* ebaabar. Air gl*s tkrougk tb* aa*-l# aa* b liters par aisut* at searured by a calibrated rnfstsTi tkis aaa auffielMt to violently ugatate tne liquid, do epplent*ry sir ms introduced iaaaaueh as taa etove supply **a aaple for tb* aalaale ixygea ra^ui rv*ata. Iks ear* observed for benawer and, since there eere ao aent.-.a, <11 sere held for tea days observation. Ik* data are shoe* ia Table VI. GBRN002911 f TOWOLDMON0002002 To: HotM- -o Ibaoieal -a^Laj It. Iimii, KUtourl Inaftr laboratories Jartlflcata of loal jsla t./ 1 5/o4 - T-**-7 ULz.lAi A) Oral U,, (kU, lUzad Sax) tka Oral for aala aad faaala rat* aas placsd at t>oOO olHlgraoa par kllofrM IU loasr aad Of par Halt a of >J75 to 8.>*5 ailligraaa par kilogras. tko saopiasad aaa claaaad aa prsctlaallp aoa-toxic bp oral lagsatlaa la aala aad fala rats* I) Oral MLB (kbblto, Rlxad Sax) Tka Mini -- lat'.al Oral >>oaa for aala and faaala rabbi to aaa fsuod to ba graatar tkaa 1000 oilllgrmaa par ctlogroo aad iaaa taaa 1J00 oilligraaa par xilograa. Tka eospouod aaa claaaad aa olldlp toxic bp oral iagaatioa ia aala aad faaala rabbits. 0) SCLa Abaarptloa MLD (babbits, Rlxad Sa Bm kilai letoal Oosa bp &la ibaorptloa ia aala and faaala rabbits aas food to ba graatar t.-.sa OlO ailllgraaa par xilograa aad laas cias }?S0 allllgraao par kilagrao* Tha coopouad aas claaaad aa sllgbtlp toxic bp altla abaarptloa ia aala aad faaala rabbits* D) Skis Irrltatioa (babbiU) flM oaopoMi aas claasad as s aodarats bkla irritaat abaa appliad wdilatsd to iatsat rabbit skis. Tka average ai` r- score aas 4*0 ad of a pooslbla 9 ia taaatp-foar boara* S ^a Irrltatioa (Babblta) fta aoapoaad aas elassad as s alld to aodarats apa irritant* Tka avaroga aaxiaua aeora aas 2).S out of a poasibla HO is oas boor. n Vapor lobslstioo (Mala bats) All *<' survived tha sis acur sxpoaura aa sail aa tbe following tsa dap ilnmtiat pariod* Zt san i--111 il tint tbs vapors aara alifbtlp toxic aadar coaditiaoo of tba tsat. lamia uackaTocK _\ ~a BTt tcttcn P- GBRN002912 TOWOLDMONOOQ2003 s*. Leaia, nrnui tw|ir Ul Mitort-- iMfiwti of laal/aia - Pa* 4 (2/13/44 / - r-64-7 TAILS I tsa ojul 10,, or - 145* foa sa SMple Tad Palliated Aglaal_*o_;.| ai*fc. a o. 1- Ttaa It <- Ttault <- Halt X-. Mala >- Paaalt 6- Paaalt 7- Mala 3- Mala 0 Taenia ic- r>it 11- Mala ' 12- Mala 15- ftacit 14- Taaa It i>- Mala lb- Mala 17- ftaalt IS* Ttaal a 19- Mala 20- Mala 21> 245 .40 225 25c :>o 260 --5 253 240 260 225 2 55 240 <50 .20 225 240 245 Soaa >,010 .,010 .,ao ,,.no ',010 c,510 6,510 6,510 6,510 0, 510 7.940 7,940 7,940 7, >40 7,940 10,000 10,00c 10, OuC 10,000 10,000 ............. ftif... ium*ad 01 ad Sam tad Sara itad lartltad Sam tad wl4 Sard tad 01 ad iurtltad Surtlttd 01 ad 01 td Snrttttd Surd tad 01 ad Jlad ^iad 01ad Sled 0UCS4&I0M - Tbe Oral U>, for Bale aid faaale rata a placed at 6600 allll*raaa par <a.lcrM rltt lower cad upper Ualta of >575 to 82 85 aiUirmaa par u.3r*a. TSo oaapoaad aia aVaaaad aa practically aoa-taxle bp oral Laceatisa la aala aad faaale rata. latlNl tlM aaa oaa to tear lays* ta^. apapteae laeluded padMlly iaerae*i.a a--traaaa. ilarrbaa, traaora, aad mb of op to teeatyfoar boara Aaratloe. At aatopap ttara aaa raaal, liter, aad pwlaoaerp ijptml* bp oaeroaeopie aaaalaatloa. BBRN002913 TOWOLDMONOOQ2005 lartlPlaat* of Aaalpaia - Paga 6 (2/1J/64) T-6*-7 Tim m sji kxmxicn usual jos*. or 'ra-ii^' T ill* i&jOdPTXCB XV Bi&BITS aMpla ippllad Sadlluta* iblffl-jg; -T,#g X - Faaala 2 - Mala J - Faaala 4 - Mala 5 - Faaala i Mala right .Ui. 2. d 5.1 2.6 5.0 2.6 5.1 doaa Hii/.H: 651 I.V. l5dC 2510 5930 b>10 talgat Cbaaga 5 0a p a Oatar ...........!l:........... 01 0.0 - 0.2 - 0.4 riu iurrtrod ourriTad jurriTad lurrlaad Jlod -- 2 Dapa Jlt4 2 Btji OtiCDUXCV - Tkm Hiatmm Lath*! Joaa bp Skla AbaarptlM La aala aad faaala rabbita aaa foaad to ba |mtr **- 2510 atlLlgraaa par ktlograa aad 1m tbaa )99Q milligrams psr Tba mil iraal aaa alaaaad aa aiigatlp toxie bp atdji absorptloa la aala tad (Mali rabbit*. terrlval tlaa tms taa dapa far aataala #5 aad *6. Toxic apaptoaa Lseladad traaors, loaa .f r?atita, lpapaaa, aad lacraaaiag oaaKnaaa. it aatapap taara aaa li ar iiaaoleratioa aad r*aal eoagastioo bp aaeroaaopla aaaaiaatloa. GBRN002915 TOWOLDMONOOQ2007 * HaiMito Skalctl St* LmU| Mitwrl !ou(tr Laborstoria* Csrtiflcats of Analysis Pigs 6 (2/1}/U> r-64-7 TA 3L 4 V ns liumrios in aAaBXK ajtjj or 're-145' ipl* (0.1 Kllll-itsr, Appllsd Oadilutsd Asianl Sunbsr 1 Hour Nuns rl cal STSloatioa At Ths but Of 4 Ho'irs 56 Maura 7* Sours 110 Hours lod Hours t 22 15 34 - 0 2 27 14 i 4 0 *% ' Zc 16 10 7 2 0 4*?rAgs 1 16.0 10.6 6.6 -'.0 0.0 JIoCJo-I.N * Ths eniouad sss classed as s alii to aodsrts s/s irritant. tbs sTsrsgs jeors ns 2 5.6 out sf s posslbls 110 Is oas Now. Cosaldsrsbls dlseoefort ns shown iaasdlstsly upsa Application* Aftsr ns bnr tasr* mi nodsrat* lserinatlon, slight adsaa, slid to sodsrsts rsdasaa of ths fmpssr 1 :onjuactiTis, sold iris coagsstico, sad slight eonssl dsllasa* for sa sTsrsgs seors of IJ.b. Oisenarfs eanssd is tsooty-four kars u.i oagsstloa rsduesd. lo*s.--.ag ths assrogs sr -rs to 18.0. Iris sad saron ssrs aoroal ia fits liys. A slight dsgrss of rsdasss ns still prssnt la tio .ostaaess. GBRN002917 TOWOLDMONOOQ2008 To> Mm--to liiaalaal 41; ipwty lit Kiitovfl ToMfor Laboratories Certificate of Aaalyaia - rag* ) (2/l}/&4) T-04-7 ! i 11 I VI IMUUTIOM ur 'W-145* VAKii aT TS Av*rig* Tp*ratar* laaid* Cfcaabcr .................................................... 7?* ?. Average Melativ* daaidity Xu.li Chaobcr...................................... `4 1 Aaount Of laaplv - To dtart...................................... i*covar*d............................... Vaporised r Left la Apparatus............................... 150*0 c* 140*5 ee 1*5 c (1.0*) Asia*1_ JJo. i a* 1 - Mai* , 2 - Nal* 5 Mai* 4 - Mai* ..if}!.. survived -arTl*d Jurvivad ju roved _____ _vfeajrr t loa*_ JUrtaf_ loo* due o* fort la tan to flft*a siaat** ... Mild aaaal ducaerg* ... L-rtaargy ... Occasional aaallo* breathing Mo eeakaesa of eoese^aeac*. DISCUSbUM - All ani**la jrrld taa 'i* sour jzpoaur* aa **11 as th* following tan lay observation period* It aaa concluded taat th* vapor* >*r* slightly toxic under eoaditioaa of th* t*at. Inhalation of U>* vapors eaua*d oe* liacoafort out th* aaiaals **r aot aeakened to aay *xtaat. ho Bronchial ral* *r other evtleace of reapir^tjry taflaaaatloa aaa acted either iaaadiately foliosing exposure or luring th* tea day osservetion ported. SBRN002918 TOWOLDMONOOQ2009