Document Ed4ppDEeqEK2aZo6zrz216k8g

4 project no; RZr-RT ounger Laboratories BiocUemUk ... PliaimacfilofUti ... AnaLfUi Vw _ 123 CLIFF CAVE ROAD Saint Louis, Mo, 63129 PHONCI TIldin 6*2 540 Ge/dificate &j Analtf&Li 3 ./ SUBJKT ~ hRoCLik ; .{ , / J"# l3th* 1964 .. Taxleologleal Investigation Of: NCI - 29 S Monsanto Sanpls Humber 57 Monsanto Project Munbap 1-64-49 ' sL FR-o') STUDY COMDOCTH) I'D* - , . , .. ' . V * ;? ' ' ); Monsanto Company, St* Louis, Missouri '. .' ' '. % I XXPEHDCBfTAL PBOCDUBI .. ............ ..... ... ............... A) Oral U>90 (Rats, Mix#4 Sax) The ondiluted compound ana fed by stonaoh tabs to Spragna-Dsaley strain albino sale and fesale rats* .. After the approxlsate Mlalsua Lethal Dose aas determined, groups of sale and female rats aero fed In Increasing doses at increments of 0*1 fractional log intervals at four levels designed to blanket the toxicity range thereby supplying data for calculation of the LD9a which aas done according to a modification of the aethod of S* J. do Beer* Observations were made for toxlo symptoms and the viscera of the animals that succuabed aero examined maeroscopleally* The data are shown in Table X* B) Skin Absorption MU) (Babbits, Mixed Sex) The undiluted compound was applied in increasing doses at increments of 0*2 fractional log intervals to the closely clipped, intact akin of Sea Zealand . white male and female rabbits* .- The treated areas were covered aith plastic strips and the animals plaeed in wooden stocks for periods up to twentyfoar hours, after which tine they were assigned to individual cages* Observations were made for toxic symptoms and the viscera of the animals that succumbed sere examined macresoopieally* The data are shown la Table ZZ* 6BRNQ02919 TU* mfid*nril report i* not to b* ua*d in any form of *dvortuin( without written panniminn TOWOLDMONOOQ2010 Tot XoBHBto Coapoay - - St* Louis, Missouri Younger Laboratories Certificate of Analysis - Page 2 (6/13/64) - 7-64*49 BCPEBIMEBTAL PBOCBOBI - (Continasd) 6) Skim Xrritatioa (Babbits) ' Tbs undiluted eoapoaad aas appliod to tbs elippsd, iataet akia of slbiao rabbit# sod renoved after twenty-four hours* Tbs applieatioa aas eorsrsd with plastic stripe to rwtard evaporation sad avoid eoataaiaatioa* Obaorratioaa wars aado orsr a period of several daps for irrltatioa* The data, scored according to tho astbod of Draiso, Voodard aad Celverp (Journal of Phara* aad Exp. Therapeutics, Toluae 82, Dossaber, 1944) are shoes ia Table ZZZ* D) Bps Irrltatioa (Babbits) 0*1 Milliliter of uadllatsd saaple eas placed ia tho conjunctival sac of tho right spa of each of three albino rabbits and observatioaa aado ever a period of several daps for iaflaaaatloa* Tho opes vers rinsed with oara isotonic saliae solution after twenty-four hours* She data, scored according to tho aethod of Draiso, ot al, are shown ia Table IT* ' , >. X) Taper Inhalation (Male Bats) Sis aature aalo rats were placed ia a aetal chaaber ef 35*liters capacity aad exposed for six hours to a concentrated ataosphere of vapors produced by passing a strsaa of air through 130*nlllilitars of the eoapound contained ia a 300-ailliliter Srleaaeper flask* Vapors froa the flask passed into a oae liter bottle to reaove droplets and then into tho chaaber* Air flow through tho saaple was six liters per aiaate as aassured by a calibrated rotaaeter* This was sufficient to violently agitate the liquid* Vo seppleaeatary air was introduced iaaaauch as the above supply was aaple for tho aaiaals oxygen requireaeats* The aaiaals were observed for behavior aad, since there were ao deaths, all were held for tea daps observation* The data are shows ia Table T* SOMMABY - /- / `> A) Oral LDSC (Bats, Mixed Sex) " ' \ Tho Oral U>99 for aalo aad feaalo rats was placed at 4200 ailligraaa per kilograa with lower aad upper Halts of 3740 to 4700 ailligraaa per kilograa* The eoapoaad was classed as slightly toxic by oral iagestioa ia aalo aad fesalo rats* B) Skis Absorption KLD (Babbits, Mixed Sox) Tho Mialaua Lethal Dose by Skia Absorption ia aalo aad finale rabbits was found to bo greater than 301 ailligraaa per kilograa aad less than 794 ailligraas per kilograa* The eoapoaad was classed as aoderately toxic by akia absorption ia sale aad finale rabbito* 6BRN002920 TOWOLDMONOOQ2011 fas Konsuto Coapnnp ) St* Louia, Mleaourl lounger laboratories Certificate of Analpeio - Pax# 3 (6/13/64) - 1-64-49 SUMUXT - (Continued) C) Skim IrrlUUoa (Babbits) The eoapoaad aaa olaaaod aa a aodarat# akia Irritant abas applied undiluted to iataot rabbit aids* .. . . The irirai* mrlaua aoara me 4*3 eat of a poaalbla la twentp-four hours. ` .' 0) Irrltatioa (Babblta) ;.*(< The eoapound aaa classed aa a aodarat# epe lrritaat* The iTinft aaartaaa aeora aaa 41*6 oat of a poaalbla 110 la taentp-four hoars* D Taper lahalatloa (Mala Bata) 111 aalaala aorrirad tha alz hoar exposure aa aall aa tha following tea dap observation parted* It na eoaeladad that tha Tapora ware praetieallp bob-toxle oadar eondltloaa omf athva_ at.a__o_ at.. , TOONGEB IABOBAIOBZB The material in this report is to be used in development of the product and may be given to responsible sales cents:-', but it is not to be ured by (h im in advertising copy. l'r- toxicity aro to be referred as before to the M-tdirsl bent in St. Louis for reply. -- Monsanto Cherntral Compe - . SBRN002921 TOWOLDMONOOQ2012 i. iii.iUk i -.< 111 --jU m tlM d iiil . Tot Moosaato Coapaap ' St. Louis, Missouri Touofer Laboratories Certificate of inalpsis - Paft 4 (6/23/44) - I-64-49 IllLI Z IBS OBLL LD,, Of 'MCS-295' F02 BUS Staple Fad tfadilutad V Aalul Mo.'- Sax Tslfht Ost| Dote Mfc/.iS2 Fata 1- Nnlt 220 3160 2- Fault 223 3160 > Malt 230 3160 4- Malt 215 3160 3- Fault 220 3160 Survived Survived Survived Survived Survived 6- Fault 230 3960 Died 7- Halt 243 3980 Survived 8- Malt , 235. 3980 ! Survived 1 9- Fault 225 3980 10- Fault 220 3980 Died Survived - 11- Malt 12- Malt 13- Fault 14- Fault 13- Malt 230 240 215 230 245~ 3010 3010 3010 3010 3010 Died Sled Died Died Died 16- Malt 240 6310 Bled 17- Fault 230 6310 Died 18- Fault 245 6310 , Died 19- Malt 230 6310 Died 20- Malt 255 6310 Died DISCUSSXOI - Tha Oral U>99 for ult tad fault rat waa placed at 4200 ailllfraae par kilogru with lowar aad apptr Halts of 3740 to 4700 alllifnaa par kilograa* Tha coapouad aaa olasaed at slightlp toxic bp oral iatestloa it aalt aad fault rata. . y, V sr Survival tiu aaa tat to four daps with aost deaths oeourrltf it throw ta foor daps. Toxic spaptoas lacludtd stvtrt diarrhea, increasing weakness, traoors, aad collapse* it aatopap thtrt was rtaal aad liver hpptrasda at wall at iaflaautioa of the gastric aacoaa bp ueroseopie exaainatioa. GBRN002922 TOWOLDMONOOQ2013 Tot Monsanto Coapaap St* Louis, Missouri . Toungor Laboratorlos Csrtlfiests of Aaalpsia - Pago 5 (6/15/64) - 1*64*49 ~ lilil Q THX MINIMUM LETHAL DOSX Of 'MCS- 295* XT SKIN ABSOBPTZfli XV BASIS Saaplo Applisd Undilutod .. Aaiaal Mo. - Sa 1 - Halo 2 - Poaalo 3 - Halo \ 4 - Posalo 5 - Mala 6 - Pasalo 7 - Mala ftight JXU 3.1 2.6 3.2 2.9 3.4 2.X 3.1 Doss isi/Sti 501 794 1260 2000 3160 3010 7940 Toight Chango 3 Daps Lator Kg. 0.0 - 0.2 - 0.3 mmmmm 0*3 mmmmm ---- * _______ m____ ___ 5urvivod Dlod -- 6 Daps Dlod -- 7 Daps Diod -- A Daps Diod -- 5 Dap* Dlod -- 4 Daps Diod ~ 3 Daps - DISCUSSION - Tho Mininas Lothal Doss bp Skin Absorptioa is sals sad fsaalo rabbits was found to bo groator than 901 ailligraas par kiiograa and loss than 794 ailligraaa par kiiograa. Tho eoapoaad *as elassod as aodoratolp tonio bp skia absorptioa im aalo sad foasis rabbito. Survival tiao saa thrso to aovoa daps. Asldo fsroa rodueod appotito aad sodorato lothargp thoro aas littlo sho* of toxieltp until approziaatolp twoatp-four hours proeodiag doath. Iacroasiag ooakaoss, trenors, and dpspaoa appoarod at this tins. . Autopsp fladiaga iacludod livor with poliowish eoloratioa and roaal hpporoatia. GBRN002923 TOWOLDMONOOQ2014 Tot Monsanto Coupony ' St. Louis, Missouri Tounger laboratories Certificate of Analysis - Pact 6 (6/13/64) - T-64-49 mu iiz SKIM IRBIIATIOI Dt BABBITS AITEB APPLICATIOM OP 'MCS-295' Saaplt Applied Undiluted AniaalMaaber ' 1 goay 11 21 32 Nuaerieal Iraluation At The Bad Of 24 Hours jS. Hours J2 Hours 120_Hours 4321 42 20 5421 l6fl Hours 0 0 0 Average 1*3 4*3 3.0 2.0 0.6 0.0 DISCUS5IQS - The coapovad was classed as a noderate skim irritant them applied undiluted to iataet rabbit skim* The average score sas 4*3 oat of a possible 6 in twenty-four hours. Barely perceptible to well-defined redness sas present after one hour. Overnight there was noderate redness and edeaa for an average score of 4*3* There was no blistering. Inflaaaatioa gradually reduced following reaoval of the compound se that within five days only a trace of erytheaa retained on two aninals. \ GBRN00292M TOWOLDMONOOQ2015 Tot Monsanto Company ' St* Louis, Missouri lounger Laboratories Certificate of Analysis - Pago 7 (6/12/64) - T-64-49 - imi it . STS XBBXTATION Of BABBITS ARB AFPLICATXOM OF 'HCS-295* Sasplo (0.1 Milliliter) Applied Undiluted ASanaienMaml wMwauaswtemr 1 2 3 Average iuserieal Bvaluatioa At The Sad Of ljtour 24 Hours fB Hours 7? Hours 120. Hoars 168 Hours 35 47 41 30 13 2$ 36 23 13 32 42 33 22 12 6 0 0 31*6 41*6 34*3 23*6 13*0 2.0 DISCUSSXOS - The compound was olassed as a noderate eye irritant* The average aaxiaua score ass 41*6 out of a possible 110 in twenty four hours* Discomfort ns noderate immediately following application* . Mild redness and edema, noderate laoriaatioa, and aild dullness of the corneal area developed within one hour* Congestion Increased aoaewbnt in tsentyfour hours at which tine the average score was 41*6* Discharge had ceased and edema was still aild but iris details sots not as clear coapared to the one hoar reading, fithin seven days two animals sere free of iaflaaaation* Slight redness of the conjunctivas was still present on the third anlaal* V GBRN002925 TOWOLDMONOOQ2016 Te Monsanto Coapaay : - St* Louie, Missouri lounger laboratories Certificate of Analysis - Page 8 (6/13/64) - 1-64-49 TitLI T INHALATION Of 'MCS- 295' VAPOBS BT BAT* Average Teaperature Xaside Chaaber............ ......................... ............ 79* f* Average Belatire Huaidity Xaside Chaaber .................. *................. .. 49 % Aaoumt Of Saaple -- To Start **....... Becovered ....................*......... .. Vaporised or left la apparatus............ ............ .. 150 so 149 so 1 ee (0*6)f) Aniaal Wo* - Sea 1- Male . 2- Male ' 3- Male 4- Male 5- Male 6- Male mm. ,rater - Survived Survived Survived Survived Survived Survived -- ..SfrfSrffHgPf.Paring.Exposure Moraal breathing rate Vo pawing at the aose NO nasal discharge Vo discoafort Vo woakaoss* DISCUSSXOI All aaiaals survived the six hour exposure as well as the following tea dap observation period* Xt was concluded that the vapors were practically non-toxic under conditions of the test* The aaiaals appeared unaffected bp the vapors* They shoved no diseonfort during exposure* No inflaaaatioa of the ocular or aaaal aacosao was detected when the aaiaals were reaoved frea the chamber* She tea day observation period was uneventful* . BBRN002926 TOWOLDMONOOQ2017 TOWOLDMONOOQ2018 to: Xosuito Jiapeap tit. loul*, Rlaaourl Xouagar Umti(i1m ^irtUlati of haalpaia rag* //-/" * .'-r-+*7'; tovaxmu. pwemnt - (c*ati*u*d) C) tola Irrltatia* (tobbdta) Tfc* uadilatad ai aapllad to th* clipped, intaat a*ia of ilbtao MMlta ik raaovad tfUr th.trfwr iain. Ik* * covered oitft plaatie atrip* to retard evaporation aad avoid eoatamaatioa. Ch*#rv*tloa* a*r **# <-ar period of ooveral dapo for IrriUtloa. Th* data, ecored accordiag to the aotbod or 3r*iaa, to*lari aad Calvary (Journal of Hwera. aad toy. Therapeutics, Volua* S3, ~oca*0ar, 1J44) ar* show* la fable ill. 0; ya Irritation (tobbitaj 0.1 ttllllliter of undiluted aoaplo aaa plaeai la th* eoajaaotlval aae of tha right *** of aaoh of taro* aleiao raboite aad obaarratioa* aado over a parlad of aovoral dajra for iaflaaaatloa, Th* apes oar* rlaaad vita aara laotoal* aalla* aolutiaa aftor t**atpfe*r hoars. Th* data, ooorad aaeordiag to th* aothad of Orala*, at al, ar* aho* la Tabla IV. . B Taacr iahalatioa (Mala itata) Six aaui.-o aal* nta oor* placed ta a aatal ehaabar of 35 litor* eapaaltp tad txpoaod for all boar* to a coeeaot rated ataoapharv of vap*ra produced ' by pwm a atroaa of air through 150 millliter* of th* *--j am i eontelaad la a 2X^*111111 tor tall for* gaa aaahlng bottl* ilM frit tad dlaa. Vapor* fra* tha bottla paa**d lato a oaa liter bottl* to raaovo droplet* aad tha* lab* th* ehaabar. hlr fl** through tha maple aaa 7 liter* par ala*ta aa aaaaurod bp a calibrated r*t*a*t*r. Ini* aaa eufflolaat to violaatlp agitata th* liquid, to aupplaaaatarp air *** l* troda*ad laaaaueh aa th* above aapplp **a **pl* for th* aalaala jxpgaa raqalrmeat*. Th* aalaalo oar* observed far bahavler aad, alaea th*r* oar* a* death*, ell ar* bald for tea dope obaai'vatlaa. Th* data ar* atom la Tahl* V. .: < UriiJ 4) Oral Up (tot*, Mixed **) 1h* Oral U)M for aal* aad famlo rota vea plaeod at S900 miligraaa jor kilograa ita l**r aad appar limta of ""iSO to Ij.I-JS miligraaa par kilograa. ib* caspomd **a elaaaad aa preatiealljr aoa-teme bp oral lagastioa la aal* aaa faaal* rate. TOWOLDMONOOQ2019 TOWOLDMONOOQ2020 Toi ita it. Mala,- mamourl - UtwU CtfttflMU af Aaal/aie - Paa 4 (7/2V*4) - Y-4V77 -f : mu m oaa to,. OF <FI- 1 5 9' JOV MXS Iff] Fad UadUatad Iml M> - Aaa alfbt 9a. 1- raoal# 2- r#aala V Mala V Nala V faaala a- faaala 7- Mala a- Nala 9- Faaala 10- Faaala U- Nala 12- Nala IV Faaala IV Faaala IV Nala i* Mia 17- Faaala IV Faaala 1** Nala 20- Nala 210 215 230 220 210 205 235 240 220 215 245 .50 225 215 240 2 to 215 220 235 230 Oaaa HiJLfts. , 310 a,310 6,310 6, 310 6,310 7,940 7,940 7,940 7.940 7,9to 10,000 10, XO 10,000 10,000 10, ox 12,600 12,600 12,oOO 12,600 12.600 Itu 2wria Aarrlrad Aarrlrad Aarrlrad Sarrtrad 01 ad Aarrlrad Aarrlrad 01 ad Aarrlrad Aarrlrad 01ad Olad Olad Aarrlrad Olad Olad Olad Olad Olad SISCQUION - Tha Oral U,a tor aala add f-.-aala rata aaa ylarad at S.900 eilUraaa ;ar kilaraa dth loaar aad uppar Uavta jf 7, '30 to 10,145 aUllgraaa par kllogma. Iba oaapaaad aaa clanad aa praatiaally aoe-taxla by oral lsfaatlaa la aala aad faaala raaa. Marital tlM aaa aaratal Mura to four daya ntt aoat daatbs ocearrla* la to to tkraa daya. Ttoda ^aptaaa Laaladad aarart 4larrb>, lacraaaiag aaakaaaa, oollapaa, af foar to 4kt Mara 4utt(o> e* At antopay tbara aaa l&Oaaaatloa of tba gaatrla aacoaa ud raoal ayparaMa. 6BRNQ02930 TOWOLDMONOOQ2021 To: Noa^ato Coapuy it. laui*, Kleeourl Imo| UMntarlM Sertl/ioot# or Aoil;di - rij* ./!>4, - - c a- ; ni:i ii au NIJIIWM L^ruAL JC4A .f TM- : j BT iKIN ABiOBPTION I* BABBITS Saaple Applied Uodlluted bo. - in rsMli *le rail* Nolo rail* Hols eight Axi. `. 3 t.z z.i 2. a Jomm HiAfti 631 1UU. 1580 2510 2510 3* eight CbmAge 5 Do yd loter _____ Si*....... >*2 0.2 0.0 .......... Fit* Survived Survived Survived Died -- 2 Days Died -- 5 Doye Died - Overaight DISCtUalOR - The MlalMB Letfcol Does by bula Absorption 11 Mil ud Mi rabbits ess rouod to bo (rwtt.- Uu 1)40 HUUnH per cxlogrea sod lees Uuo 2)10 llllgrodo or mir-- Ibe nrfoiii see loosed as oaldly toxlo bp dda absorption is sole sod Tooele rabbits. Survival ties sue imnl hour* to thro* dope. Toxic eye?toss included leereading -->--< treoore, salivation, ana collapse. At autopsy tier* mo puiaonsry byporeola sad 11*or discoloration. GBRN002931 f TOWOLDMONOOQ2022 iu IrtT4 "t _____ Toaagor Wtoratarlaa Cartiftaaba of Aaalyala - hit 6 (7/20/14) r-o^-77 TAILS Z21 ua itounai xi hbib Aim appuoatioh or - ijj Saapla ippilad Cadi1m tod l_Jwbor ueorlaal evaluation At Tho fed Of 11 Sour 24- latry AO lotrt J2 3oera 120 'doura 168 .fse 1 2 3 Avorugo 2.3 4-3 .`.6 2.0 1.3 0.0 213CU&5ION - Tbo eoapouad uuo ciasavd aa a aooarvta atin irritact Aaa ippllad uadllutad to iatact rabbit akia- Zha arart|a aeort >%a 4-3 oat of a poatlbla 6 la tooaty-foar boura. Aftar aaa boar thara aaa vall-daflaad radaaaa aith oaa inataaaa of vary alight ad aaa. la t--foar boara aodarata radaaaa aad alight aaalllag lacToaoad tha initial avaraga aaoia of 2.3 to 4-3. Infiaaaatloa gradually raduaad following raaoval of (ka applloatlaa. tartly paraaptlbla to alight orytbaaa proaaat aftar fivo daya tiaappaarad vltfela aavaa daya. BBRN002932 Taugar Utirmrln Cartlflente of uiiyiti - Page 7 (7/20/64) - x-e*-77 r * 3 1 s iv <3S IRS TATIOH I* RABBITS ATT-Ji AKf-UIiTIvN J TB- 1)9' fasple (0.1 HlXliilter) Applied Undiluted Bffeal "ter 1 dour *-- irlcal evaluation At The ted Of doura 4d_doura 71 Bourn |.0_doura X honoura X 2 5 Average >1 dti 17.3 ia 21 :i 20.0 XI 11 ij 14.3 6 12 * 9.0 0 4 4 2.0 0 J 0 0.0 OZSCU&SUN - The eonpound aaa cleaned aa a aodarata eye irritant* The average **rl"1* aeora aan 17*3 out of a poealble no la oaa Sour. Oieeoa/nrt aaa aodarata lenediately following application. Blight swelling ate laa riantlo*. aodarata radaaaa of the conjunctive#, and nil lrla eongeatlon aara noted in aa hour, dineharge e aaaad ennljkt and trie clarity leproved. A alight degree of redeeaa that reaauad ca too aniaala after five 4eye dlaappaarad althla eevan dnye. 6BRN002933 TOWOLDMON0002025 Younger Laboratories iocUtmidti ... PUa/unaaolafinU ... AnaLfsU ias cnirr cavi ioad SAINT LOCU, MO, 68139 PBONBI TILDSM 6.2 S 40 AnahjAil August Utht 1964 SUBJECT - Toxicological Investigation Of: Fydrsul 2 80 Koussato Sample Number 102 Monsanto Project Number Y-64-91 .. STUDY CONDUCTS) TOR Monsanto Company, 5t. Louis, Missouri QCPaHIKZNTAL FROCi-URi - k) Oral LD,0 (Rats, Mixsd IBs undiluted eoi albino sale ube to oprague-Daviley strain > After the and fesale log inte; supplying modification /boss van determined, groups of male _____ doses at increments of 0.1 fractional I?els designed to blanket the toxicity range thereby ition of the LD90 which was done according to a of E* J. de Beer. Observations were made for toxic symptoms and the viseera of the animals that suecuabed sere examined aaeroscopieally. The data are shorn in Table I* B) Skin Absorption KLD (Babbits, Mixed Sex) The undiluted compound earn applied in increasing doses at increments of 0.2 fractional log intervals to the closely dipped, intact skin of Nee Zealand shite aale and feaale rabbits. The treated areas sere covered with plastic stripe and the animals placed In sooden stocks for periods up to twentyfour hours, after which time they sere assigned to individual cages* Observations sere aade for toxic symptoss and the viscera of the sniasls that aueesabsd sere examined maeroecopically. The date art ahoaa in Thbls II. . TU* nport ii net to bo and in ujr tarn *1 dwiHn'u without writan GBRN002935 TOWOLDMONOOQ2026 Tei Menusto Company . St. Louis, Missouri Younger Laboratories Cartiflcato of Analysis - Page 2 (8/11/64) - -64-91 BCP2DG3fTAL PBOCE5UBE - (Continued) C) fids Irritatioa (Babbits) The usdilutod compound was appliad to tha clipped, intact skis of albino rabbits and removed after twenty-four hours. The application was covered with plastie strips to retard evaporation and avoid contamination. Observations were aade over a period of several days for irritation. Hi* data, scored according to th* aethod of Praise, Woodard and Calvary (Journal of Ffcara. and xp Therapeutics, Volume 82, December, 1944) are shown in Table III. D) i$r* Irritatioa (Babbits) 0.1 Milliliter of undiluted sample was placed in th* conjunctival sac of the right eye of each of three albino rabbits and observations nads over a period of several days for inflammation. The eyes were rinsed with vara isotonic saline solution after twenty-four hours. Hie data, scored according to th* method of Draize, et al, are shown is Table IV. 2) Vapor Inhalation - 350* 7. (Male Bats) Six mature male rats were placed in a metal chamber of 35 liters capacity and exposed for six hours to a concentrated atmosphere of vapors produced by passing a stream of air through 130-milliliters of the eoapound contained in a 300-millilizer rlenmeyer flask placed in a sand bath on a hot plate and the contents maintained at a temperature of 330* 7. Vapors from th* flask passed into a train of two one-liter bottles to remove droplets and then into the chamber. Air flow through th* sample was five liters per minute as measured by a calibrated rotameter. This was sufficient to violently agitate the liquid. No supplementary air was introduced inasmuch as th* above supply was ample for the entasis oxygen requirements. Th* animla were observed for behavior and, sine* there were no deaths, all were held for ten days observation. The data are shown in Table V. SDMMAH - Pydraul 280 A) Oral LDj0 (Bats, Mixed Sex) Th* Oral LDj0 for mala and female rats was plaeed at 11,730 milligrams per kilogram with lower and upper limits of 9,370 to 14,390 milligrams per kilogram. Th* eoapound was classed ms practically non-toxic by oral ingestion in male and female rats. GBRN002936 TOWOLDMONOOQ2027 fet Monsanto Conpanyf* St* Louis, Missouri lounger Laboratories Cartificate of Analysis - Page 3 (S/ll/64) - T-64-91 SUMttBT - (Continued) B) akin absorption KU (Babbits, Mixed Sex) Sts Mininun Lethal Dose by Skin Absorption in Bale and fssale rabbits was found to be greater than 1260 nllllgraaa per kilogren and less than 200C ailligruis per kilograx. The conpound sas classed as nildly toxic by skin absorption in aale and feoale rabbits* C) Skin Irritation (Rabbits) Ow conpound vas classed as a noderate skin irritant* The average naxinun score sas 3*3 out of s possible 8 in twenty-four hours. 0) Sye Irritation (Babbits) Iht eonpound was classed as a noderate eye irritant* The average naxinun neore ana 31*3 out of a poasible 110 in twenty-four hours* } Vapor Inhalation 330* P. (Hals Sats) All aninals survived the six hour exposurs as wsll as the following ten day observation period* It sas concluded that the vapors sera nildly toxic under conditions of the test* YCUlIjiii 03/.TOid Th" the p; o;.'u: but it is n' source ot' . l io v-ri : : in devefo-njent of zl-.c .:ontsrt3 The fceat is it. Louis /or reply S Mnnssato Gheeucai Company GBRN002937 TOWOLDMONOOQ2028 Tot Noonanta Company St. Louie, Missouri Younger Laboratories Certificate of Analysis - Pag* 4 (8/11/64) - T-64-91 UBU Z THE OBAL LDjo 07 'Pydreul 280' FOB BATS Sample Fad Undiluted Animal No* - Sax ieight Qm. Dose Ng* / Kg. Fate 1- Female 2- Female > Male 4* Male 5- Female 6- Female 7- Male 8- Male 9- Female 10- Female 11- Male 12- Male . 13- Female 14- Female 15- Male 16- Male 17- Female 16- Female 19- Male 20- Male 220 250 . 245 235 225 230 250 245 215 235 250 260 225 210 24C 235 220 225 240 250 7,940 7,940 7,940 7,940 7,940 Survived Survived Survived Died Survived 10,000 10,00c lc.ooc 10,000 10,000 Survived Survived Survived Survived Died I2,6u0 12,60c 12,600 12,60c 12,oGv, Survived . Died Died Died Survived 15,800 15.8CC 1560v 15,800 15,800 Died Died Died Survived Died DISCUSSION - The Oral LD90 for male aad faaala rats aaa placed at 11,750 milligrams par kilogram with loaar aad upper liaita of 9,570 to 14,390 allligraaa par kilogram. The compound aaa elaaaad aa practically naa-texie by oral Ingestion la sale and faaala rata* Survival time aaa several hours to six daya aith moat deaths occurring In tnroe to four days* Toxic sysptoaa included loaa of appetite, severe diarrhea, incraaaiag aeakaaaa, aad collapaa* At autopsy there aaa renal aad lirer hyperemia as sell as inflammation of the gastrie mueoaa* GBRN002938 TOWOLDMONOOQ2029 To> Monsanto Cospanj St* Lout*, Missouri lounger Labor*torts* C*rttflc*t* of Analyst* - Page $ (8/11/64) - 1-6^91 T A B L S ZI IKK MXXXMOM LETHAL LOSE OP 'Pydraul 2 8 0* BT SKIN ABoOHPTIuN IN ABBITS Saapl* Appliad Undiluted t No. - Sex 1 - Mala 2 - Female 3 - Male 4 " Female 5 - Mai* 6 - Female ; sight Kg. 2.7 2.3 3.0 2*4 2.6 2.8 Doss Hg- / Kg. 1,260 2,000 3,160 5,oio 7,940 12,600 1 O eight Change 5 Days Later _ ____ - 0.1 - 0.2 0*4 0*4 - 0.5 Fat* Survived Died -- 8 Days Died -- 7 Days Died -- 8 Days Died -- 5 Days Died -- 7 Days DISCUSSION - Tha Hintbub Lathat Dos* by Skin Absorption in aal* and ftaala rabbit* va* found to b* greater than 1260 nilligmas per kilograa and lea* than 2000 milligrams per kilogram. The eoapound va* classed a* sildly toxic by akin absorption in sal* and feoala rabbits* Survival tia# vas five to eight days. ' Toxie syaptoas included reduced appetite, weakness in two to three days, and useular iapairaant particularly noticeable in the neek auaelaa causing the head to droop* At autopsy there was liver discoloration and pulsonary hyperwsia saeroscopically* GBRN002939 TOWOLDMONOOQ2030 To: Hoaaaato Company J St. Louis, Hiaeouri lounger Laboratories Certificate of Analysis - Page 6 (6/11/64) - Y-64-91 TABU III SKXX IBSZXATZQM ZH BABBITS AFTEH APPLICATION OF 'Fydraul 280* Sample Applied Undiluted Animal Number Numerical Evaluation At The Bad Of 1 Hour 24 Hours 46 Hours ?2 Houra 120 Hours l6d_Hours 1 13 2 0u 2 1 3 3 2 1 Wr 3 24 3 2 1 c Average 1.3 3.3 2.6 2.0 0.6 0.0 0ISC3S5I0N - Th* eoapouad was claaa*d as a moderate akin irritant. Th* average maximum aeore was 3.3 out of a possible 6 la twenty-four hours. After one hour there was barely perceptible to well-defined redness with no edema. Aell-defined to moderate erythema vith very alight edema in twenty-four hours produced an average score of 3*) following removal of the compound the average score reduced to 0.6 la five days at which time barely percentlble erythema was still present oa two aaimals. bbrno02940 TOWOLDMONOOQ2031 . Tot Konaanto Coopan. ... . .. St. Looia, Miaaouri lounger Lahoretoriae Certificata of Aaalyaia - Pago 7 {8/11/64) - 1-64-91 TABLE XV STS XBBXTATXOM XV BABBITS A7TS APPLICATION OT 'Pydraul 2 8 0' Sanpla (0.1 Killilltar) Applied Undiluted Anloal Munber Numerical iwaluntion At The Skid Of 1 Hoar 24 Bow 48 Hours 72 Hours 120 Houra 168 Houra 1 2 3 Awaraga 35 53 26 31.3 29 25 19 24.3 21 18 12 17.0 15 11 8 11. 3 9 4 4 5.6 4 2 0 2.0 DISCUSSION - The eoapouad waa elasaad aa a aodarata aye irritant. Tha average aaxiaua aeora oaa 31*5 out of a poaaibla 110 in twenty four houra. Coaaidarabla diaeoafort developed following adainiatration. Slight edaoa and discharge, aodarata erythaaa of tha palpabral conjunctiva#, and aild irla eongaation and cornaal dullnaaa wara notad within an hour. Edaaa and diacharga diaappaarad overnight. Improvement continuad following irrigation landing to an awaraga aeora of 2.0 in aawan days. GBRN0D2941 TOWOLDMONOOQ2032 Tot Monsanto Companj f St. Louis, Missouri lounger laboratories Certificate of Analysis - Page 8 (8/11/64) - 1-6^91 TA BL V INHALATION OT 'Fydraul 280' VAFG3J BT 2AT3 (35o* r.) Average Teaperature Iaaide Chanter ............... ...................... Average Relative Humidity Iaaide Chafer........................... 79* 7. 53 % Amount Of Sample -- To Start ............................................ 150.0 ce Becovered ................................................. 132.0 ee Vaporised or left ia apparatus....... 7*5 Condaasate ia 1st literbottle........ 10*5 ee Condensate ia 2ad literbottle ..... 0.0 ee cc(5.%) Aaiaal_No. T-Sex 1 - Male 2 - Male 3 - Male 4 - Male 5 - Male 6 - Male Fate Survived Survived Survived Survived Survived Survived Obeerrations During ibcpoaure Moderate discomfort in thirty minutes .. Occasional irregular breathing ..* Moderate nasal discharge ... Some weakness but no danger of eollapse. CISCUSSION - AH animals survived the six hour exposure as well as the following ten day observation period. It was concluded that the vapors were aildly toxic under conditions of the test. A temperature of 350* 7. was reached in approximately twenty ainutes. The blue color changed to pale green and gradually turned to light brown in . four hours. A moderate degree of base was present ia the chamber throughout the test. Discomfort increased with time. Moderately severe inflammation of nasal sad ocular mucosae warn noted when the animals were removed. All bad a mild degree of bronchial rales. There was no gasping but breathing was somewhat difficult. Inflammation reduced ia twenty-four hours and within three to four days breathing was nearly normal. The appeared in good condition at the end of the tea day observation period. BBRNO02942 TOWOLDMONOOQ2033 7T.0. Yr^'3-9 :j\ l Younger Laboratories Biockemiiii ... Phaimact>lo<fiiU.... AttahfiU 123 CLIFF CAVE ROAD Saint Louis. Mo, 63129 Phone: tilden- 6-2510 SUBJECT - PfCSML -3/i Toxicological Xaveatigatlom Oft MCI 31t Monmaate Saapl# Hoabcr 146 Monsanto Project Busbar 1-64-133 November 12 th, 1964 STUDY COMDUCTED 708 - , .( Monsanto Company, St Louie, Kiasoarl EXPEBZXX8T4L PBOCZDBEE . - - ' A) Oral LD,, (Bata, Klxod Sax) The undiluted compound aaa fed by etoaech take to Spragur-Davley etraia albino sale and feaale rata* After the approximate Minimum Lethal Dose warn determined, groups of aale and feaale rats aere fed in Increasing doses at increments of 0*1 fractional log interrala at four levels designed to blanket the toxicity range thereby supplying data for calculation of the LDsa vhleh was done according to a modification of the method of E* J* do Beer* Observations were made for toxic symptoms and the viscera of the animals that succumbed were examined mmeroseopieally* The data are shewn in Table Xe B) Skin Absorption MLS (Babbits, Mixed Sex) . The undiluted compound was applied in increasing doses at increaents of 0*8 fractional leg intervals te the closely clipped, intact skin of Hew Zealand white aale and feaale rabbits* The treated areas were covered with plastic strips and the animals placed la wooden stocks for periods up to twenty-four hours, after which time they were assigned te individual cagea* Observations were made for toxic symptoms and the viscera of the animals that succumbed were examined mmeroseopieally* The data are ahowa in Table XX* BBRN002943 eeB&doitut report is Dot to bo umJ u> ony fora of idwtiui without written pomuaaon TOWOLDMONOOQ2034 Tot Monsanto Coapaay St* Louis, Missouri lounger Laborstori*a Certificate of Analysis - Pag* 2 (1V12/64) - 1-64-153 EXPEBDGXtAl PS0C220PX - (Continued) C) Skis Zrritatloa (Babbits) ' The undiluted ooapouad was applied to th* slipped, intact akin of albino rabbits and reaoved after twentyfoar hoars* Iho application was oovered with plaatio strips to retard evaporation and avoid cootadnation* Observations were sad# over a period of several daya for irritation* Th* data, scored according to tho sethod of Drains, Voodard and Calvary (Journal of Pham, and bp* Therapeutics, Tolua* 82, December, 1944) aro shown in Table Hie D) Eye Irritation (Babbits) 0*1 Milliliter of undiluted sasple was placed in th* conjunctival sae of ths right eye of eaeh of thro* albino rabbits and observations aid* over a period of several days for inflassatioa* tte eyes were rinsed with warn isotonic saline solution after tveatyfour hours* Th* data, scored according to tho nethod of Drain*, *t al, aro shown in Table IT* ' - . - ' S) Tapor Inhalation (Male Bats) Tour 150-gren sal* rats wer* plaeod in a glass dosiceator, 250 an in dlaaeter, and exposed for six hours to a concentrated ataospher* of vapors produced by passing a streaa of air through 100 ailliliters of th* coapound contained in a 250-ailliliter Erlenaeyor flask* Tapors froa th* flask passed into s one-liter bottle to roaov* droplets and then into th* ehaaber* Air flow through the saaple was five liters per ainute as aeasurod by a calibrated rotaaeter* This was suffieiaat to violently agitate the liquid* Mo supplementary air was introduced inasmuch as the above supply eas asple for th* aaiaals oxygen requiroaeats* The aniaale were observed for behavior and, since there were no deaths, all were held for tea days observation* The data are shown in Table T* SUMMAST MCI 31?. ' ;. ^. j' A) Oral LD,t (Bats, Mixed Sex) " The Oral ID** for aal* and feaal* rats was placed at 6500 ailligraas per kilograa with lower and upper Units of 5460 fes 7755 nilligraaa per kilograa* The ooapouad was classed as practically aoa-toxlo by oral Ingestion la sale and feaal* rats* B) Skin Absorption MU) (Babbits, Mixed Sex) The Miniaua Lethal Dos* by Skin Absorption in nale and feaal* rabbits was found to be greater than 2000 ailligraas per kilograa and less than 3l6o ailligrsns per kilograa* The cospound was classed as slightly toxie by akin absorption in aal* and feaal*. rabbits* . BBRN00Z9M4 TOWOLDMONOOQ2035 Tot Monsanto Coopaay ' fit. Louis, Missouri lounger Laboratories Certificate of Analysis - Pago 3 (11/12/&A) - 1-64-133 SUMKAST (Continued) C) Skin Irritation (Babbits) The eoapouad ons classed as a slight skin irritant ahea applied undiluted to intaot rabbit akin* The average --Ttnun score was 1*3 out of a possible 8 in twenty*-four hours* 0) Eye irritation (Babbits) The eoapouad was classed as a slight eye irritant* . The average sort nun score was 13*0 out of a possible 110 in twenty-four hours* E) Vapor Inhalation (Mala Bats) All anlaals survived the six hour exposure as well as the following ten day observation period* It was concluded that the vapors were practically non-toxic under conditions of the test* . ' TOUMSEB LABORATOBZES V\ GBRN002945 TOWOLDMONOOQ2036 Tot Koasaato Coapaay St. Louis, Kiooouri lounger Laboratories Certificate of Analysis - Pip 4 (11/12/64) - 1-64-153 TAB LI Z THE OBAL LD,, OF 'MC8 312* FOB BAS Saaple Fo4 Undiluted Aaiaal Bo* - Sox Weight Doss .S.U. . Sfc/.Sb 1- Foaalo 2* Foaalo 3- Mala 4* N*ls 5- Foaalo 6- Foaalo 7- Halo 8- Mala 9 Foaalo 10- Foaalo 11- Hals 12- Bale 13- Foaalo 14- Foaalo 15- Nolo 16- Halo 17- Foaalo 18- Foaalo 19- Halo 20- Halo 195 5,010 210 5,010 230 5,010 22$ 5,010 220 5,010 210 6,310 240 6,310 230 6,310 . 20S 6,310 215 6,310 250 7,940 230 7,940 215 7,940 22$ 7,940 245 7,940 230 10,000 210 10,000 22$ 10,000 240 10,000 250 10,000 rats ooasaoosoooooi Survived Disd Survived Survived Survived Died Survived Survived Died Survived Survived Died -Died Died Survived Died Died Died Died Died DXSCUSSIOB - The Oral LD,S for sals aad foaalo rats was plaeod at 6500 ailligraas per kilogrea with lover aad upper Halts of 460 to 7735 Killigrmse par kilograa* Tbs ooapoaad ,faaals rats* i slassod as practically aoa-toxic by oral ingestion ia aalo aad /\ V \ Survival tias saa oas to foar days with aost deaths occurring ia two days* > Toxio syaptoaa iaoladod severe diarrhea, treaors, dyspnea, and oollapss* At autopsy there ass inflaaaatioa of tho gastric aucosa aad roaal hyporoaia aacroscopieally. 6BRN0029M6 TOWOLDMONOOQ2037 Tot Moasaato Cospaay * St* Louis, RUaouri lounger Laboratories Csrtifloats of Analysis - Pago 5 (11/12/64) " 1-64-133 mu ix '* THS KLHDam LRBAL DOSS or *MCS 312' BT SKIS ABSOBPTXOM IS RABBITS . Soaplo Applied Sadilatad ^ ' Aaisal Rb* - 3as sight If ' Doss */** { Weight Chang* 3 Bays Later EC* juts 1 - Hals 2 yeaals 3 - Mala 4 - resale 5 - Hals 6 - resale 2.7 794 0.1 3*1 1240 - 0.1 2.S . 2000 ' - 0*3 v 2.7 3160 * 0.4 2.4 3010 - 0.4 2.S 7940 -- Survived Survived , Survived Died -- 4 Bays Bled -- 4 Bays Biad -- 4 Bays DISCUSSIC* - -.......... ............. The Minimus Lsthal Boas bp Skin Absorptloa la sals aad fsaals rabbits vaa fouad to bs grsatsr thaa 2000 allllgraaa par kllograa aad Isas thaa 3160 nilligraaa par kUSgraa* . As eoapooad saa elaassd aa slightly toxic by akia absorptloa la sals aad fsaals rabbits* Survival tlas aas four, to sis days* Toxio syaptoas iaoludsd gradaal lsss of appstits, iaersasiag asakaass, aad treaors. Violsat convulsions aad sqasaliag wars aotsd approxlaatsly twenty-four hours bafors death* At autopsy thars vara heaorrhagi* araas la tbs luags as vail as llvtr dissoloratioa aad renal congestion sacroseopicslly. x -l .i v ..." ' v.. . GBRN0029U7 TOWOLDMONOOQ2038 Tot Monsanto Coapenp ' ' St* Louis, Missouri lounger Laboratories Csrtifieats of Analysis - Pt< 6 (11/12/64) - 1-64-133 T A B L I ZZX skib isamnoi zb babbits Arm application or 'mcs 312* Ssapls Applied Undiluted / Bttnerieal Evaluation At Ths Bad Of Aniaal Wuaber !. 1 Hoar 24 Hours 43 Hours 72 Hours 12Q Hours 1 01 1 0 0 1 02 1 1 0 3 01 0 0 0 Average i 0*0 1*3 * ' V DXSCVSSXOI - ' 0*3 t t 0.3 0*0 * ./ \ TBs eoapouad was elasssd as a slight akin irritant Asa applisd undilutsd ts intact rabbit Ain* Ths srorags aaxlaua scors vas 1*3 out of a possibls 8 ia twenty-four hours* " Vo skin changes vsrs aotsd ia oas hour* Overnight there was barely psrcsptibls rsdassa oa two aalaals sad well-defined redness oa ths third aniaal for aa average scors of 1*3* Vo edeaa dereloped* VLthla seventy-two hours two aoiaala were free of ooler and all received a score of sera la five daps* A \t \ V Ai \ BBRN0029M8 TOWOLDMONOOQ2039 Tot Koaaaato Coop*ay St. Loaia, Xlaooari Yoooger Laboratorloa Certificate of Aaalyaia - page 8 (11/12/64) - T-64-133 I1IL1 V ixhalaxicv or a 312* tapobs bi un Average Twperataro Xaolde Chaaber .............. ........... . Average Selative Huaidity Iaaldo Chaaber ....................... * 1i\ Aaoaat Of Saaple -- To Start ...*... 100*0 eo Beeoverod........ *......... 99.5 * ' Taporlsod *.................. 0*3 00 (0*5%) 7* P* 82 % _ Ail ol So* - SC 1 - Kilo 2 - Halo 3 " Mala 4 - Halo nto Svrvlvod SarrlTod Survived Sorvired Obaervatioae Dvrlac Scpoeore lo naaal diaehart* Vo dyapaaa .* ' Kild lethargy Xo veakaaaa or diaeaofort Ailoilo app*ar waaffeoted* . DISCCS3I0V - ... All aaiaala aurvived tho elx hoar axpoaaro aa wall aa tho folloviag tea day ohaerratioa period* .- It no ooaeladed that the vapore aero praotioally ao>toxie wader ooaditioao of the teat* Aa oeatioaed la the table, the aaiaala appeared to be waaffeoted by the aiz hoar expoaare* Dlaeoafort oaa at a adalana aad tho oaly ehaago la behaTior na olid lethargy after approtdaately no boor* Tho tea day obaemtioa period woo uaeventfil* 6BRN002950 TOWOLDMONOOQ2040 Younger Laboratories BiocUeml&U... PUaimaad&fi&U... AnalfiU v t 133 CLIFF CAVE ROAD Saint Louis. Mo. 63139 PBONEI TILDIN 6-3540 SUBJECT - fyoRkUL ll< Toxicological Investigation Ofi MCE 39 5 Monsanto Saaple BUaber 244 Moasanto Project Humber I-65-213 JAnaU7 10th, 1966 STUDT CONDUCT!!) FOB Monsanto Company, St* Louis, Missouri EXPERIMENTAL PBOCEHJEE - .' . A) Oral LD,,, (Bats, Mixed Sex) -' As undiluted eoapouad was fed by stooaeh tubs to Spragur-Davley strain albiao ala and fenale rats* . After the approximate Miniaus Lethal Dose was deterained, groups of male and female rats sere fed la increasing doses at inereaents ef 0*1 fractional log intervals at four levels designed to blanket the toxicity range thereby supplying data for calculation ef the LD99 which was done according to a modification of the aethod of E* J* de Beer* Observations were aade for toxic symptoms and the viscera of the aniaala that succumbed were exaained aacroseopieally* . The data are shown in Table I* . B) Oral MU) (Babbits, Mixed Sax) As undiluted eoapouad was fed in increasing doses at inereaents of 0*2 . fractional leg intervals by stomach tube to Mew Zealand white Bale and female rabbits* . ., . . Observations were ands for toxic syaptoas and the viseera of the animals that succuaibed were examined aacroseopieally* -- The data are shown in Able II. '' GBRN002951 TU* oon&UatUl report i* et to U *d < **T * < *d**rt>* wiko*t writt** (n>M TOWOLDMONOOQ2041 To: Monsanto Company St. Louis, Missouri Younger Laboratories Certificate of Analysis - Page 2 (1/11/66) " T-6>-213 EXPERIMENTAL PROCEDURE - (Continued) C) Skin Absorption KLD (Rabbits, Mined Sex) The undiluted compound was applied in increasing doses at increments of 0*2 fractional log intervals to the closely clipped, intact skin of Ne* Zealand white male and female rabbits* The treated areas sere eovered with plastic strips and the aninals placed in wooden stocks for periods up to twenty-four hours, after which tine they were assigned to individual cages* . Observations were sad# for toxic symptoms and the viscera of the animals that succumbed were examined aaeroscopieally* The data are shown in Table HI* D) Skin Irritation (Rabbits, Mixed Sex) The undiluted compound was applied to the clipped, intact skin of male and female albino rabbits and removed after twenty-four hours* The application was covered with plastic strips to retard evaporation and avoid contamination* Observations were made over a period of several days for irritation* The data, scored according to the method of Draize, Voodard and Calvary (Journal of Fharm* and Exp* Therapeutics, Volume 82, Decanter, 1944) are shown in Table IV* E) Eye Irritation (Rabbits, Mixed Sex) 0*1 Milliliter of undiluted sample was placed in the conjunctival sae of the right eye of three albino rabbits and observations made 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 Draize, et al, are shown in Table V* F) Vapor Inhalation (Hale Bats) Pour mature male rats were placed in a metal chamber of 35 liters capacity and exposed for six hours te a concentrated atmosphere of vapors produced by passing a stream of air through 100 milliliters of the compound contained in a 300 milliliter Erlenmeyer flask* Vapors from the flask passed into a one liter bottle to remove droplets and then into the chamber* Air flow through the sample was five liters per minute as measured by a cali brated rotameter* This was sufficient to violently agitate the liquid* Me supplementary air was introduced inasmuch as the above supply was ample for the animals oxygen requirements* The animals were observed for behavior and, since there were no deaths, all were held for ten days observation* The data are shown in Table VI* 6BRN002952 TOWOLDMONOOQ2042 To: Monsanto Company St. Louis, Missouri lounger Laboratories Certificate of Analysis - Page 3 (1/11/6) - 1-63-213 SUMMARY M_C S_ 5 95 A) Oral LD,0 (fiats. Mixed Sex) The Oral IDJ9 for male and female rats *as placed at 4615 milligrams per kilogram with loeer and upper limits of 4060 to 52^0 milligrams per kilogram. The compound was classed as slightly toxic by oral ingestion in male and female rats. B) Oral MLD (Rabbits, Mixed Sex) The Minimum Lethal Oral Dose for.male and female rabbits was found to be greater than 1530 milligrams per kilogram and less than 2310 milligraas per kilogram. - The compound nas classed as slightly toxle by oral ingestion in male and female rabbits. C) Skin Absorption MID (Rabbits, Mixed Sex) The Minimum Lethal Dose by skin absorption in male and female rabbits eas found to be greater than 2510 milligrams per kilogram and less than 3980 milligraas per kilogram. The compound was classed as slightly toxic by skin absorption in male and female rabbits. D) Skin Irritation (Sabbits, Mixed Sex) The compound was classed as non-irritating when applied undiluted to the intact skin of male and female rabbits. E) Dye Irritation (Rabbits, Mixed Sex) The compound was classed as a slight eye irritant in male and female rabbits. The average maximum score was 6.3 out of a possible 110 in one hour. T) Vapor Inhalation (Kale fiats) All animals survived the six hour exposure as well as the following ten day observation period. It was concluded that the vapors were practically non-toxic under conditions of the test. Y0UN3ES laboratories GBRN0Q2953 TOWOLDMONOOQ2043 To: Monsanto Company 4 . St. Louis, Missouri . lounger Laboratories Certificate of Analysis - Page 4 (1/10/66) - 1-65-213 TABLE I THE ORAL LD ,0 0? 'MCS 395' FOR RATS Sample fed Undiluted Animal No* - Sez 1- Female 2- Male 3- Female 4- Male 5- Female 6- Male 7- Female 8- Male 9" Female 10- Male 11- Female 12- Male 13- Female 14- Male 15- Female 16- Male 17- Female 18- Male 19- Female 20- Male . Weight Ga . Dose 225 3160 240 3160 220 3160 255 5160 235 3160 260 5980 230 5980 270 5980 255 5980 255 5980 250 5010 255 5010 225 5010 265 5010 255 -- 5010 280 225 245 240 265 6310 6310 6310 6310 6310 Fate Survived Survived Survived Survived Survived Survived Died Survived Survived Survived Died Survived Died Survived Died Died Died Died Died Died DISCUSSION The Oral LD)0 for Bale and female rats was placed at 4615 milligrams per kilogram with lower and upper limits of 4060 to 526o milligrams per kilogram* The compound was elassed as slightly toxic by oral ingestion in male and female rats* SurwiTal time was several hours to three days with most deaths occurring overnight. Toxic symptoms included severe diarrhea. Increasing weakness, tremors, and collapse* At autopsy there was inflammation of the gastric mucosa and renal hyperemia macroseopically* 6BRN002954 v TOWOLDMONOOQ2044 Ji To; Monsanto Company ' St. Louis, Missouri lounger Laboratories Certificate of Analysis - page 5 (1/10/66) - y-65-213 T A B L X ZZ SHE MINIMUM LETHAL ORAL DOSE OP 'MCS 59$' FOB BABBITS Saaple Fed Undiluted i1 t . Animal No. - Sex Weight -XJLz. 1 - Feaale 2 - Hals 5 - Fenals 4 - Male v 5 - Fenale 6 - Kale 2.6 3.0 2.7 3.1 2.7 > 2.9 Doss BedLess 631 1000 1580 2510 3980 6310 = ; Weight Change 5 Days Later 0.0 0.1 - o.l - 0.4 ---w ' K0N 1 Fate Survived Survived Survived Died -- 8 Days ,, Died -- 5 Days Died -- 2 Days . DISCUSSION - . ,, . __ ^ . The Minimus Lethal Oral Dose for sale and female rabbits eas found to be greater than 1580 allligraas per kilograa and less than 2510 ailligraas per kilograa. The compound was classed as slightly toxic by oral ingestion in aale and fenals rabbits. V. v/ ' * . ' . Survival tine was two to eight days. Toxic syaptoas in aninals #4 and #5 included poor appetite in two to three days, weight loss, increasing weakness, tremors, and collapse* At autopsy there was evidence of liver dysfunction and renal hyperenia. i ienft of Thei thel tut i grCVC i u ia - c'aiZ.'j1'-'- - moot *::t t;,, Zvtvc-A -*:~3 k* toti:V mK\j. , ...-- -- . Cofflpanf GBRN002955 TOWOLDMONOOQ2045 To: Monsanto Company St.Louis, Missouri younger Laboratories Certificate of Analysis - page 6 (1/10/66) - Y-65-215 TABLE III THE MINIMUM LETHAL DOSE OF 'MCS 395' BT SKIN ABSORPTION IN RABBITS Sample Applied Undiluted No* - Sex Male Female Male Female Male Female (eight 3-0 2.5 2.8 2.* 2.5 3*1 Dose 631 1000 1580 2510 3980 6310 (eight Change 5 Days Later _____ Kfc_____ + 0.2 0.1 o.l - 0.1 * 0*3 - 0.2 Fate Survived Survived Survived Survived Died - 7 Days Died - 9 Days DISCUSSION - The Minimus Lethal Dose by Skin Absorption in sale and female rabbits vas found to be greater than 2510 milligrams per kilogram and less than 3930 milligrams per kilogram. The compound vas classed as slightly toxic by skin absorption in male and female rabbits. Survival time vas seven to nine days. Toxic symptoms in animals #5 and #6 included reduced appetite and activity in three to fonr days with increasing veakness, dyspnea, and paralysis. At autopsy the lungs vere hemorrhagic and there vas liver discoloration aacroscspically. 6BRN002956 v TOWOLDMONOOQ2046 To: Monsanto Company ' -- St* Louis, Missouri Younger Laboratories Certificate of Analysis - Page 7 (1/10/66) - 1-65-213 T A B L E IT . SKIN IRRITATION IN RABBITS AFTER APPLICATION OF *MCS 395' Saaple Applied Undiluted Animal No* - Sex Numerical Evaluation At The End Of l_Hour 24_Hours 4S_Eours J2_Hours 12g_Hours 1 - Fenale 0 0 00 2 - Male 00 00 3 - Female 0 0 O 0 0 0 0 DISCUSSION - The compound eaa classed as non-irritating to intact rabbit skin when applied undiluted* No edema or erythema developed on any of the animals as a result of a twenty-four hour exposure to the undiluted compound* All animals received a score of zero throughout the observation period. GBRN002957 TOWOLDMONOOQ2047 To: Monsanto Company St. Louis, Missouri lounger Laboratories Certificate of Analysis - page 8 (1/10/66) - 1-65-213 TABLE T ns IMITATION IN BABBITS AFTEB APPLICATION ON 'MCS 395* Sample (0*1 Milliliter) Applied Undiluted .. Animal No* - Sen ' Numerical Evaluation At The End Of 1 Hour 24 Hours 48 Hours 72 Hours 120 Hours 1 - Female 7 4 2 0 2 - Hale 74 4 0 3 - Female 11 6 4 2 0 0 0 Average 8*3 4*6 3.3 0.6 0.0 DISCUSSION - . The compound eas classed as a slight eye irritant in mala and female rabbits. The average naxinun score was 6*3 out of a possible 110 in one hoar. Little discomfort as shown immediately following application. After one hour there was slight discharge and redness, practically ao edema, and very slight corneal dullness. Iris and cornea were clear in twenty-four hours and within three days only a trace of redness of the palpebral conjunctivas remained on one animal. GBRN00295B TOWOLDMONOOQ2048 To: Monsanto Ceapany ' St. Louis, Missouri Younger Laboratories Certificate of Analysis - Page 9 (1/10/66) - 1-65-213 TABLE 71 INHALATION 07 'MCS 395' VAPORS BY RATS Average Temperature Inside Chamber ......................... Average Relative Huaidity Inside Chaaber ...................................... Amount of Sample -- To Start ................................ 100*0 ec Recovered ................... 99*7 ee Vaporized or left in equipaent................... 0*3 cc (0* 356) 7. 45 % Animal No.-Sex 1 - Male 2 - Male 3 - Male 4 " Male Tate Survived Survived Survived Survived 255snsiiss5-5sris5_SFPfiHrj. No immediate reaction ... Normal breathing rate ... No discomfort or nasal discharge ... No weakness ... Moderate lethargy after two hours* DISCUSSION All animals survived the six hour exposure as well as the following ten day observation period. It was concluded that the vapors were practically non-toxic under conditions of the test. The an-imala appeared to be unaffected by the exposure. Nasal and ocular mucosae were normal when the animals were removed from the chamber. The ten day observation period was uneventful. BBRN002959 TOWOLDMONOOQ2049 r/ sj *! / j project no: ' las CLIFF CAVE ROAD Y LV^PCRT FILE ounger aboratories Saint Lovis. Mo, 60139 Gentijficate 0^ AnaluIUiBiockeMti&U... PkcvuMacoloqi&U ... AaaJ^iU PHONSi TlLDIN 6-3 840 SUBJECT - . ... Toxicological Investigation Of: MCS>9-Q Monsanto Sample Number 176 .. . Monsanto Project Nuaber Y-66-151 1:L'.'. .. STUDY CONDUCTED FOR - V ttieo: io Monsanto Company, St. Louis, Missouri . .. October 17th, 1966 BCPESIKQfTAL P80CHHJSE - A) Oral LD90 (Rats, Mixed Sex) The undiluted compound was fed by stomach tube to Sprague-Daaley strain albino sale and feaale rats. After the approximate Minimus Lethal Dose was determined, groups of sale and female rats were fed in increasing doses at increments of 0.1 fractional log intervals at four levels designed to blanket the toxicity range thereby supplying data for calculation of the LDS0 which was dona according to a modification of the method of J. da Beer. Observations were aade for toxic syaptoas and the viscera of the animals that succumbed were examined aacroscopieally. The data are shown in Table I. B) Skin Absorption MID (Babbits, Mixed Sex) The undiluted compound was applied in increasing doses at increments of 0.2 fractional log intervals to the closely clipped, intact skin of New Zealand white male and 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 aade for toxic symptoms and the viscera of the animals that succumbed were examined aacroscopieally. The data are shown in Table II. 3BRN002960 TU* csefidmttul report w not to b* and is aay ions of advertidat without writtn permiaiaa TOWOLDMONOOQ2050 To: Monsanto Company St. Louis, Missouri founger Laboratories Certificate of Analysis - Fag* 2 (10/17/6&) Y-oo-i^i SCPEHIMZNTAL PBOCSDCBE - (Continued) C) Skin Irritation (Babbits, Mixed Sex) The undiluted compound eras applied to the clipped, intact akin of albino male and female rabbits and removed after twenty*four hours* The application was covered with plaetic strips to retard evaporation and avoid contamination. Observations were made over a period of several days for irritation. The data, scored according to the method of Draize, Woodard and Calvary (Journal of Pham, and Exp. Therapeutics, Volume 62, December, 1944) are shown in Table III. D) Eye Irritation (Babbits, Mixed Sex) 0.1 Milliliter of undiluted sample was placed in the conjunctival sac of the right eye of each of three albino male and female rabbits and observations made 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. ' S) Vapor Inhalation (Male Bats) Four mature male rats were placed in a metal chamber of 35 liters capacity 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 250-ailliliter Erlenmeyer flask. Vapors from the flask passed into a one liter bottle to remove droplets and then into the chamber. Air flow through the sample was four 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 animals were observed for behavior and since there were no deaths, all were held for ten days observation. The data are shown in Table V. SUMMAST MCS-_9_0 A) Oral LDjg (Bats, Mixed Sex) The Oral LDjq for male and female rats was placed at 5260 milligrams per kilogram with lower and upper limits of 2740 to 3680 milligrams per kilogram. The compound was classed as slightly toxic by oral ingestion in male and female rata. GBRN002961 TOWOLDMONOOQ2051 >> To: Monsanto Company St. Louis, Missouri lounger Laboratories Certificate of Analysis - Page 3 (10/17/66) - Y-66-151 7^3 SUMMABI - (Contiauad) B) gvta Absorption MLD (Babbits, Mixed Sex) The Minimus Lethal Dose by Skin Absorption in male and feoale rabbits eas found to be greater than 2000 milligrams per kilogram and less than 3160 milligrams per kilogram* The compound eas classed as slightly toxic by skin absorption in male and female rabbits* C) Skin Irritation (Babbits, Mixed Sex) The compound was classed as a slight irritant ehen applied undiluted to intact skin of male and female rabbits. The average maximum score eas 1*6 out of a possible 8 in twenty-four hours. D) Eye Irritation (Babbits, Mixed Sex) The compound was classed as a moderate eye irritant in male and female rabbits. The average maximum score was 28,0 out of a possible 110 in one hour. - S) Vapor Inhalation (Male Bats) All animals survived the six hour exposure as well as the following ten day observation period. It was coneludsd that the vapors were practically no-toxic under conditions of the test. - Y0UNGEB LABOBATOBIES e ' /J) BY: FBED M.^OONGEB .. GBRN0029&2 I TOWOLDMONOOQ2052 To: Monsanto Company - St. Louis, Missouri Younger Laboratories Certificate of Analysis - Page 4 (10/17/66) 7 Y-'-. 6-151 TA BL I THE OHAL LO ,0 OF 'MCS 9 O' FOR RATS Saaplt Fad Undiluted Animal No. - Sex feight 8a . 1- Feaale 2- Hale 3- Feaale 4- Male 5- Female 6- Male 7- Female 8- Male 9- Female 10- Male 11- Feaale 12- Male 13- Feaale ~ 14- Male It- Female 16- Male 17- Female 18- Male 19- Feaale 20- Male 215 245 230 255 210 255 220 245 225 265 215 250 230 245 220 240 235 255 225 260 Dose 2510 2510 2510 2510 2510 3160 3160 3160 3160 3160 3980 3980 3980 3980 3980 5010 5010 5010 5010 5010 ______ Fate Survived Survived Died Survived Survived Survived Died Survived Died Survived Survived Died Died Survived Died Died Died Died Died Died DISCUSSION - The Oral LD,0 for male and feaale rata was placed at 3260 milligrams per kilogram with lover and upper limits of 2740 to 3080 milligrams per kilogram. The compound was classed as slightly toxic by oral ingestion in male and female rats. Survival time was several hours to four days with most deaths occurring in two days. Toxic symptoms included weakness in two to three hours followed by tremors, dyspnea, and coma lasting for several hours. At autopsy there were hemorrhagic areas in the lungs and renal congestion macroscopically. GBRNQ02963 TOWOLDMONOOQ2053 / To: Monsanto Company St. Louis, Missouri younger Laboratories Certificate of Analysis - Page 5 (10/17/66) - 7-66-151 / T A B L II THE MINIMUM LETHAL DOSE OF 'MCS 90* BY SKIN ABSORPTION IN BABBITS Saaple Applied Undiluted Animal No. - Sex 1 - Male 2 - Female 3 - Male 4 - Female 3 - Male 6 - Female Weight .Ui. 2.8 2.3 2.9 2.5 2.8 2.6 Dose 501 794 1260 2000 3160 5010 Weight Change 5 Days Later _______ ____________ 0.1 0.2 0.0 - 0.2 - 0.4 -- Fate Survived Survived Survived Survived Died -- 6 Days Died -- 2 Days DISCUSSIC* The Minimus Lethal Dose by Skin Absorption in sale and feoale rabbits was found to be greater than 2000 silligraas per kilogram and less than 3160 milligrams per kilogram. The compound was classed as slightly toxic by skin absorption in male and female rabbits. Surriral time was two to six days. Toxic symptoms included weakness is twenty-four to forty-eight hours, loss of appetite, and tremors. At autopsy there earn pulmonary congestion; otherwise no visceral changes of consequence were noted nacroseopieally. BBRN00296H i TOWOLDMONOOQ2054 7^ To: Monsanto Coapany St. Louis, Missouri lounger Laboratories Certificate of Analysis - Page 6 (10/17/66) - 'f-66-151 ^ TABLE III SKIN HABITATION IN BABBITS AFTER APPLICATION OF 'MCS 90* Sanple Applied Undiluted Aaijal.No..Sejt Nuaerlcal Evaluation At The End Of 1 Hour 2^ Hours 48_Hours 72 Hours 120 Hours 1 - Male 2 - Feaale 3 - Male Average 0 110 02 11 02 2 1 0.0 1.6 1.3 0.6 0 0 0 0.0 DISCUSSION The cospouad eas classed as a slight irritant ehea applied undiluted to iataet akin of male and feaale rabbits. The average oaxisua score was 1.6 out of a possible 8 in twenty-four hours. No changes were noted at the end of one hour. Slight redness on all animals and two instances of slight edeaa were reeorded in twenty*four hours. One aniaal was given a score of zero in three days and all were free of inflaaaation within five days. GBRND02965 TOWOLDMONOOQ2055 7V7 To: Monsanto Company St. Louis, Missouri Younger Laboratories Certificate of Analysis - Page 7 (10/17/66) - y-66-151 TABLE IV EXE HABITATION IN BABBITS AFTEH APPLICATION OF 'MCS 90' Sample (0.1 Milliliter) Applied Undiluted Numerical Evaluation At The End Of Animal Mo. - Sex 1 Hour 24 Hours 4S_Hours 72 Hours 120_Hours 1 - Male 2 - Female 3 - Male Average 29 24 31 28.0 20 17 24 20.3 13 9 15 12.3 9 4 9 7.3 4 0 4 2.6 l68_Hours 0 0 0 0.0 DISCUSSION - ' The eonpound ns classed as a moderate eye irritant in male and female rabbits. The average --score mas 28.0 out of a possible 110 in one hour. There was blinking but no paving at the eyes following application. Moderate erythema, edema with mild eversion of the lids, copious laeriaatioa, and moderate corneal cloudiness developed within one hour. Discharge nearly ceased overnight and iris clarity inproved. Edema disappeared within three days and only slight erythema remained on two animals after five days. BBRNG02966 TOWOLDMONOOQ2056 ' ^ To: Monsanto Company St. Louis, Missouri Younger Laboratories Certificate of Analysis - Page 3 (10/17/66) - f-66-ljl TABLE V Average Temperature Inside Chamber ............................................. Average Belative Humidity Inside Chamber................................. 77* E. 51 X Amount of Sample -- To start....................... Recovered ........... Vaporized or left in equipment........... 100.0 ee 99*9 cc 0.1 ce (0.1%) Animal Wo. - Sex ____ Fate....................... Observations During Exposure 1 - Male 2 - Male 3 - Male 4 - Male Survived Survived Survived Survived Mo initial effect ... Normal respiration ... No discomfort ... No nasal or ocular inflammation ... Moderate lethargy. DISCUSSION All animals survived the six hour exposure as well as the following ten day observation period. It was concluded that the vapors were practically non-toxic under conditions of the test. The animals appeared to be relatively unaffected during exposure. The eyes remained open and respiration was normal. Nasal mucosae were free of inflammation when examined upon removal of the animals from the chamber. No respiratory complications developed during the tea day observation period. GBRN002967 TOWOLDMONOOQ2057 Younger Laboratories ftifrrffttnult.... piiMmeusdoqi&U ... iAnalfUi. 133 CLIFF CAVE ROAD Saint Louis, Mo, 63is9 PRONCt TILDKN 6*2140 Ge/difycate a^ Awzlftid' SUBJECT - November 9th, 1966 Toxicological XaTMtlgatioB Of: FIDRAUL F- 9 Moasaato Sample Number 184 MoBsaato Project Number T-66-159 A STUDY CONDUCTED FOR Monsanto Company, St. Louis, Missouri EXPERIMENTAL PRCCfflURE - A) Oral LD90 (Bats, Mixed Ssx} The undiluted eoapouad wa albino aals and female ra to aprague-Dawley strain After the approxii female rats *er log icterrals supplying data modificatioa o le ess determined, groups of male and fs at increments of 0*1 fractional __to blanket the toxicity range thereby calculation of V.e Ui0 which was done secerning tc a ' L. J. de Beer. Observations wer that succumbed oxic symptoms snd the viscera of the animals macroseopieally. The data are sfaova in Table I. B) Skin Absorption MLD (Babbits, Mixed Sex) The undiluted compound was applied in increasing doses at increments of C.2 fractional log intervals to the closely clipped, intact skin of Now Lealand shite male and fesale rabbits. The treated areas were covered with plastic strips snd the animals placed in ooden stocks for periods up to twenty-four heurs, after which time they were assigned to individual cages. Observations were mad# for tocic symptoms and the viscera of the animals that succumbed were examined macroseopieally. The data are shown ia Table II. GBRN0D296B TOWOLDMONOOQ2058 To: Monsanto Compsay ' St. Louis. Missouri Younger Laboratories Certificate of Analysis - Fags 2 (11/9/66) - Y-66-159 SUMMARY fydhaul9 . A) Oral Ujo (Bats, Mixed Ssx) lbs Oral LD,0 for ssl* sad female rats sas placsd at 11,200 milligrams par kilogram with lowar sad uppar limits of 9.655 to 12,770 milligrams per kilogram. Iha compound was classed as praetiesllj bob-toxic by oral iagestioa in sale sad famsle rats. BJ Skin Absorption KLD (Babbits, Mixed Sex) The Minimus Lethal Dos* by Skin Absorption in mala and femal* rabbits was found to be greater than 501 milligrams par kilogram and less than 794 milligrams par kilogram. Hie compound was classed as moderately toxic by skia absorption in male and female rabbits. YCUNSui LABOiUTOitlni j* - ' BY: FRtD M. fOUNGL* -- 5-.... t .; i*' T.'. ; ho .. v .. r r.'.f r.t in j;;. te::;,;:;- rj , ; men: in St. Louis /cv x^i .'<'.3 co; i. M^hsactu Company GBRN002969 TOWOLDMONOOQ2059 To: Monsanto Company St. Louis, Missouri Younger Laboratories Certificate of Analysis - Page 5 (11/9/661 - r-66-159 TA3La 1 TH& OhaL LD,0 OF 'PYDkAU*. F-?' iW AATw Staple Fsd Bndilutad daal No. - Sex Aeight Gb 1- Feaale 2- Hale J- Feaale 4- Male 5- Feaale 6- Male 7- Feaale 8- Hale 9- Feaale lO Male 11- Feaale 12- Male 19- Feaale 14- Kale 19- Feaale l6- Kale 17- Feaale 18- Kale 19- Fesale 20- Kale 21? 26u 225 240 250 245 220 255 215 25o 250 245 220 26C 225 :% 245 22? 240 Dose Sss/JSti 7.94C 7,940 7,940 7.940 7,940 . lC.Ou. 10,000 10,000 cco lw| CwVe 12,6Cw 12,6uu 12,600 12,6-C 12,600 15, S'- li owC l?,bC\15 f S'v-V Fate survived survived Survived survived Survived Survives Died Survived Died Survived Died Died Survived survived Died *'ii4er. Died Died jied DISCUSSION - The Oral LDjg fr n^ female rts was plaeed at ll,2oC ailIi.-rtR--: :er fcdiagram with lowsr and upper Halts of 9,855 to 12,770 ailligraos per kilogram. The coapound was classed as practically non-toxic by oral ingestion in sale ano fcaale rata. Survival tlae was two to five days, To^e ayaptoae Included weakness after several hours, diarrhea, loss of appetite, treaora, and dyspnea. At autopsy there was renal and liver hyperenia by aaeroscople exaaination. BBRN002970 TOWOLDMONOOQ2060 To: Monsanto Company fife. Lsats( Missouri Tomagar Laboratories Certifieats of Analysis - Page 4 (11/9/66) " r-66-159 TABLE XX THE MINIMUM LLTHAL DOSE OF 'PYDKAUL F- 9' BT SKIN ABSORPTION IN BABBIT* Sample Applied Undiluted Animal No. Sex height il:. dose *-A*Ei Weight Change 3 Days Later ____ _______ 1 - Female 2.3 316 2 - Male 2.6 501 3 - Female 2.4 794 4 - Male 2.8 126c 5 - Female 2.4 20C.C 6 - Male 2.6 3160 0.0 - 0.2 - 0.3 - 0.3 - 0.2 - 0.4 Fate Survived Survived Died -- 7 -'ys Died -- 7 Days Died -- 6 Days Died -- 5 Days DISCUSSION - The Minioua Lethal Done by Skin Absorption in oale and female rabbits sas found to be greater than 301 milligrams per kilogram and less fenan 794 milligrams per kilogram. Die compound sas classed as moderately toxic by skin absorption in sale and female rabbits. Survival time vas five to seven days. Toxic symptoms included loss of appetite, lethargy, and noticeable aeakness in too to three days* At aatopsy there ass pulmonary hyperemia; otherwise no visceral changes of conseqaases were noted naeroseopieally. GBRN002971 TOWOLDMONOOQ2061 Younger Laboratories BiocUerniiti.. Pltabmacolotji&U ... AttahpUl 123 CLIFF CAVE ROAD Saint Louis. Mo, 63129 . PHONE: TILDES 6-2540 Qe/dilkxde Anal^iii hovexter it:., 19pl iUBJECT - Toxicclogieal Investigation Of: FYD RAUL 2S0 Monsanto dam pie Number 186 Monsanto Project Humber Y-66-161 STUDY Cuioucr.^ FoR Monsanto Company, St. Louis, Missouri fiCPSAlMzJvI/vL PaLCiDiikL - A) Oral LDjo (fiats, Mixed Sex The undiluted compound a male and female rata. .rogue-Dailey stroir. .iit_r.c After the appro: female rats wed intervale at ff supplying data modification o ae^e'Mi, Ted in levels se was determined, groups of male and fees at increments of D.l fractional lor blanket the toxicity range thereby n of the LDjo which was done according to a f 1. J. de Seer. Observations were" toxic symptoms and the viscer? succumbed were examined croeeopicaily. the animals that The data are shown in Table 1. B; Skin Absorption KLD (Rabbits, Mixed Dex) The undiluted compound was applied in increasing doses at ineresents of C.2 fractional log intervals to the closely clipped, intact akin of New Zealand white male and female rabbits. ' The treated areas were oovered with plastic strips and the animals plaeeo in wooden stocks for periods up to twenty-four hours, after which time they were assigned to individual cages. Observations sere mads for toxie symptoms and the viscera of tne animals that succumbed mere examined macroacopically. The data are shown in Table IZ. 6BRN002980 TOWOLDMONOOQ2062 Tot Monsanto Conpany it. Louis, Missouri Younger Laborstoriss Csrtifiests ef Analysis - fags 2 (11/9/66) - I-66-161 SUMMARY FYLSAUL 2 8 0 A} Oral U90 (Hats, Mixed Sex) The Oral LDjo for sale and female rats eas placed at 6,440 milligrams per kilogram with lower and upper liaits of 6835 to 10,3t0 ailligrams per kilogram. The coapound was classed as practically son-toxic by oral ingestion in male and female rats. B) Skin Absorption MLS (Babbits, Mixed Sex) The Minimum Lethal Lose by Skin Absorption in male and female rabbits was found to be greater than 200u milligrams per kilogram ana less than 3160 milligrams per kllogran. The compound was classed as slightly toxic by akin absorption in male and feaale rabbits. YOUNGLR LABORATORIES BY: FKiD M.'-tOUNG-R The material in this report is to be used in development oi the product and may be given to responsible sales contacts, but it it not to be uaed by them in advertising copy. The source of this material is not to ha divulged until it appears in formal publications. No exceptions to the established rule may be made without th; reproval c: the Medical Depart* ment in St. Louis. Customtrs' inquiries uratdiug matters of toxicity are to be referred as before to the .Medical Depart? ment in St. Louis for reply. . -- Monsanto Company GBRN002981 TOWOLDMONOOQ2063 To: Monsanto Company St. Louie, Missouri Younger Labor*tori** Certificate of Analysis - Pag* 3 (11/9/66) - Y-6^l6l TABU I TH GHAL U>90 Of 'MOiUuL 280* IOH HATS Sample Fed Undiluted Animal No. - Sex height Qm . Dose Mg,/Kg, Fate 1- female 2- Kale > Female 4- Male 5- Female 6- Kale 7- Female 8- Male Female 10- Male 11- Female 12- Kale 13- Female 14- Male 15" Female 16- Kale 17- Female 18- Male 19- Female 20- hale 2u 6,310 255 6,310 23C 6,310 240 6,310 215 6,310 260 7,940 225 7.940 250 7,940 220 7.940 270 7,940 225 10,000 265 lU,<X0 230 10,tXG 25C 10,wvV 225 . 10,CoO 26c 12, tx 215 12,600 255 12,600 210 12,600 2<iu 12,600 survived Survived Survived Survived ./ied survived Sled Survived 01 ed Survived survived 4>ied *>ied survived Survived Oied Died oied Oied Oied DlSCGSsItN - The Oral w90 for aal* and female rata aaa placed at 8,440 milligrams per kilogra with lower and upper limits of 6,6J5 to 10,}80 milligrams per kilogram. The compouad eaa clasaed aa practically non-toxic by oral ingestion in male and female rata. Survival time aaa several hours to four days. Toxic symptoms included tremora after two to three hours, lethargy, loss of appetite, and collapse. At autopsy there was inflammation of the gastric mucosa aa wall as liver hyperes: 6BRN002982 J' TOWOLDMONOOQ2064 To: Monsanto Coapany St. Louis, Missouri Younger Laboratories Certificate of Analysis - Pag* 4 (11/9/66) - Y-66-161 T A S L 2 II TBS MINIMUM LOSiAL DCSi OF 'PYDBAUL 2 8 0' BT SKIN ABSOBPTICN IN BABBITS Sanpie Applied Undiluted .aal No. - Sex 1 - Hale 2 - Female 5 - Male 4 - Fsaale 5 - Male 6 - Fsaale height JLHh- 2.6 2.5 2.7 2.5 2.7 2.5 Dose 794 1260 2000 5160 5C10 7940 weight Chang 5 Days Inter ____ ________ c.o - 0.2 - 0.2 - 0.4 - u.5 - 0.5 Fate Survived Survived Survived Died - 10 ways Died -- 7 Days Died -- 7 Days DISCUSSION - --. Tha Miniaua Lathal Dose bp Skin Absorption in aale and fsaale rabbits ras found to be greater than 2000 ailligraas per kilogram sad lass than 5160 ailligraas per kilograa. The compound was classed as slightly toxic by skin absorption in aale and fesale rabbits. Survival tiae was seven to ten days. Toxic syaptoas included weakness and inactivity after tvo to three days followed by treaors and collapse. At autopsy there was liver dehydration sad discoloration as well as pulaonary congestion. GBRN0029B3 TOWOLDMONOOQ2065 Younger Laboratories BiocUenUiti ... Pkaimactdtxfi&U ... Attaly&U 123 CLIFF CAVE ROAD Saint Louis, Mo, 63129 PHONE: TlLDEN 6-2540 Q&diiicate al Analu&ti. SUBJECT - _ Toxicological Investigation Of: FIDRAUL 15 5 Monsanto Sample Number 185 Monsanto Project Nuaber f-66-l60 Norember 9th, 1966 STUD! CCNDUCTiD TOR Monsanto Company, St. Louis, Missouri BCFERIMiHTAL FfiOCSWRci - A) Oral LO,0 (Sets, Mixed The undiluted compound ale and female rataA ch\Cube to Sprague-Daaley strain albino After the app: female rats interrals at supplying da modification se mas determined, groups of male and fees at increments of L.l fractional log blanket the toxicity range thereby on of the Ll/90 which was done according to a f E. J. de Beer. Observations vr^agfl| lifr toxic syaptoms and the viscera of the animals that succumbed were examined naeroscopieally. The data are shown in Table I. B) Skin Absorption MU) (Rabbits, Mixed Sex) The undiluted compound was applied in increasing doses at increments of 0.2 fractional log intervals to the closely clipped, intact akin of New Zealand mhite male and 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 taxie symptoms end the viscera of the animals that succumbed were examined macraseopically. The data are shown in Table ZZ. . `, . GBRN002984 TU, wiMwiiil report i, aot to bo Mod ia tar him of adowrrisBC without writuo TOWOLDMONOOQ2066 To: Monsanto Coapony St. Louis, Missouri Younger laboratories Certificate of Analysis - Pago 2 {11/9/66) - t-66-160 SUMMARY PTPRAPI 13 5 A) Oral LDJ0 (Bats, Mixed Sox) Tbs Orsl LD,0 for sale sad fsasls rats sas plaeod st 4200 ailligraas par kilograa sltb lower sad uppsr Halts of 5025 to 5840 ailligraae par kilograa. Tbs eoapouad ns elassad as slightly toxic by oral lngastion la asla sad fsaala rats. B} Skin Absorption MID (Rabbits, Mixad Sex) Tbs Mlniaua Latbal Oosa by Skin Absorption in sals and faaala rabbits ns found to ba greater than 126c ailligraas per kilogzu and lass than 2000 ailligraas par kilograa. The eoapouad ns elassad as aildly toxic by skin absorption in asla and faaala rabbits. YOUNGER LABORATORIES Buy n suae wtvuvut .. . . meet ia St. Louis.Customers' inquiries regarding toxicity are to ba referred as before to the Medic asent in St Louis for reply. -- M- *onsan.to aCn_o_m.p.a.n.y GBRNQ027S5 TOWOLDMONOOQ2067 lot Monsanto Coapanp St. Louis, Missouri lounger Laboratories Certificate of Asal/sia - Pact 5 (11/9/66) - I-66-160 TABLE X TH ORAL LDi0 OP PYDRAUL 135' TOR BATS Sasple Fed Undiluted Anlaal No. - Sax eeight as. Dose Mg./Kg. Fete 1- Ftnalo 210 3160 2- Mala 235 3160 3- Foaalo 220 3160 Ar Male 245 3160 5- Feaale 215 3160 1 1 6- Male 255 3980 225 3980 8- Male 23c 3930 9- Fesale 220 3980 10- Male 265 3980 11- Feaale 215 5010 12- Male 240 5010 13- Feaale 230 5010 14- Male 265 5010 13- Feaale 225 5010 16- Male 270 6310 17- Foaalo 230 6310 18- Male 245 6310 13- Feaale 230 6310 20- Hale 265 6310 survived Survived Died Survived Survived Died Died Survived Died Survived Survived Died Died Survived Died Died Died Survived Died Died DISCUSSION - The Oral LDjo for sale aad foaalo rato aao placed at 4200 niHigraaa par kilogra* ith lever aad upper Halts of 3023 to 540 ailligraaa par kilograa. The eospouad aas classed as sllghtlp toxic bp oral lagcation la aalo aad female n Survival tlao aas aororal hears to throo daps. Toxic spaptoas included troaors la too to throo hears* diarrhea, less of appetite aad eoaa of six to eight hoars duration. At astopap there ess renal, liver, aad pulaoaarp hpperaaia la addition to laflaaaatloa of the gastrointestinal sontat. 6BRN00298& 1' TOWOLDMONOOQ2068 Toi Monsanto Company St. Louis, Missouri lounger Laboratories Csrtifieats of Analysis - Pago 4 (11/9/66) - I-6~l6o TABLE ZZ THE MINUTOM LETHAL DOGA 07 'PTDRABL 13 3' BT SKIN ABSORPTION IN RABBITS Sample Applied Undiluted Animal No. - Sex 1 - Male 2 - Female 3 - Male 4 - Female 5 - Male 6 - Female weight 2.8 2.4 3.0 2.6 2.8 2.5 Dome Hg./Kg 501 794 126o 2000 3160 5010 weight Chang* 5 Says Later _____ Sfc....................... Fate - 0.1 - 0.1 - 0.2 - 0.2 - 0.4 - c.3 Survived .survived survived Died - 11 Days Died -- 9 Dmys Died -- 8 Days DISCUSSION - The Minimum Lethal Doe# by Skis Absorption in sals and focal* rabbits was found to b* greater than 1260 allligrans pr kilogram and less than 2000 milligrams per kilogran. The compound was classed as mildly toxic by akin absorption in male and fesale rabbits. Survival time eas eight to eleven days. Toxic symptoms included reduced activity, loss of appetite, narked weakness, and collapse. At autopsy there sms liver discoloration and renal hyperemia naerofeopically. GBRN0029B7 J- TOWOLDMON0002069 Younger Laboratories 133 CLIFF CAVE ROAD Saint Loins, Mo. 63129 BiocUmi&ti'... Pk&una&loqiiti ... AnalyiU 1 Q&Uljjiccde. 0^ -AmltfUiPhones TIldin 6*2540 ttoveaber 9th, I966 SUBJECT - Toxicological Investigation Oft Prj*UL A C Monsanto -ample Nuaber 183 Monsanto Project Nuaber T-66-158 STOnT CuNJUCT-L ILK Monsanto Company, at. Louis, Missouri UCPhilMi-KTAL PkOCiDURi. - A) Oral LJjo (**ts, Mixsd -ex^ Tbs undiluted eoepound albino sale and feasts rsl e to -prague-havley strain After the appro/ MinitaMLethaJ/Jbse was deteralned, groups of sale and female rati fere fed i^i^TV^idg doses at inereaenta of C.l fractional log Intervals four levels designed to blanket the toxicity range thereby supplying data' ealcula/feon of the *DS0 ahleh ess done according to a aodificatlon of' J, de Beer. Observations were *a*"for toxic synptons and the viscera of the aainals that succusbed vere exasined saeroscopically. The data are shown in Table I* B) Skin Absorption KLD (Rabbits, Mixed 6ex; The undiluted eoepound was applied in increasing doses at lneresents of 0.2 fractional log Intervals to the elosely clipped. Intact skin of Mew Zealand white sale and feaale rabbits. The treated areas were covered with plastic strips and the <--' placdd in wooden stocks for periods up to tventy^four hours, after Aioh tine they were assigned to individual cages. Observations were aade for toxic syapteas and the viscera of the aainals that succunbed vere taained aaeroscopically. The oats are ahona in Table II. ThU rimlHmriil npnn i, nnt tn It uml i hit fi.in nf nli wiiaii, iihmi milian !! GBRN0D29B8 TOWOLDMONOOQ2070 Tot Moaaanto Company St. Louis, Missouri lounger Laboratories Certificate of Analysis - Pug* 2 (11/9/66 - T-66-15S SUMMARY - grjimn. a c A) Oral LD,o (tots, Mlxsd Ssx) Tbs Oral 1D,0 far sals sad fasale rats aas plseod at 18,920 ailligraas par kilograa slth lovar sad uppar lislts of 16,270 to 21,950 ailllgrans par kilogram. Tha eospouad sas elassad as praetieallp novtoxic bp oral iagastion in aala and fasale rats. B) Skin Absorptioa MLD (Xabbits, Mixed Sax) Tbs Minimus Lathsl Joss bp okla Absorptioa ia aala and fsasle rabbits aas found to ba graatar than 794 silligraas par kUograa sad lass than 1260 silligraas par kilograa. Bis eospouad sas elassad as aildlp to aodaratalp toxic bp akia absorption in aala and faaala rabbits. . rooNasi laboratories .1 i. Bit FRED M-lroUNOER C7> ;t The xp&terial in this report is to be used in development cj, the product and may be given to r";: risible tales contacts. but it is not to be used by tl:;r:. in r:'.'. crtl'siti.? copy. The source of this rr.nisri-'I is r.ot to 1:;' d; c'-d un*ft it appears -- Monsanto Cciapar BBRN002989 TOWOLDMONOOQ2071 Tot Monsanto Coapany St. Louis, Missouri Younger Laboratories Certificate of Analysis - Page 3 (11/9/66) - r-66-156 UBU I THL QhAL Ui0 Of f-YOhADL AC JON HATS saaplt fed Undiluted Aniaal No. - Sax eight Ga . 1- feoale 2- Kale 3- feoale 4- hale 5- feoale 6- Kale 7- feoale 6- Kale feoale 10 - Male 11- resale 12- hale 13- feoale 14- Male 15- Feoale 16- Male 17- feoale 18- hale 19- feoale 2o- Male 215 250 2-5 260 220 230 233 233 215 26w 2<5 245 220 2 6o 210 235 220 230 230 265 Jose Mg./ Kg. 12,000 12,600 12,60012,6iX 12,600 15,600 15, So*. 13,600 15,800 15,800 20,000 2w| V 2w,ooo 20,000 20, OX 25,100 23,100 23,100 23, IX 2 5, IX fate Survived survived -urvived survived Survived Survived survived -> urvived Died Survived wled Survived sled Survived ourvived sied Jied Sled sled Jied DISCUSSION - Tha Oral LS50 for sals and feaala rats was plaeod at 18,920 ailligrasa per kilogrsa with lower and upper Halts of 16,270 to 21,930 ailllgraas per kilogran. Tbs eoapouad was classed as practical1/ non-toxic by oral ingestion in sale and feaale rats. Survival tins was several hours to nine days with aost deaths occurring id three to five days. Toxic syaptoas included severe diarrhea, loss of appetite, trewora, and increasing veaknssa. . At autopsy the gastrointestinal tract was gaseous sad iaflaaaed. Liver discoloration and renal congestion wore also noted. BBRN002990 TOWOLDMONOOQ2072 To: Monsanto Coopaay iit. Louis, Missouri Touager Laboratorios Certificate of Analysis - Fag* 4 {ll/i/66) - Y-66-158 T A B L IZ THL MINIMUM LSIHA1 Di~ OF 'rTLIUUL A C ' BT SjCIK ABsOBFUkN IN fcABBITS Saapl* Applied Undiluted Aaiaal No. - ocx 1 - Male 2 - Feaale 3 - hale 4 - Feaale 3 - Male 6 - Feaale weight 2.8 2.4 3.1 2.6 2.8 2.5 Sose Kg.ZKgj 501 794 X2&v 200) 3l6t> 5olo weight Change 3 Jays later .. Kg. 0.1 o.O - C.2 - 0.5 - C.2 Fate survived survived Cied -- 9 Pays Lied - 1C Cays Lied -- 5 *ays cied -- 6 Lays DIsCUUION The Minibus Lethal 3os* by Skin Abaerptioa la sals and fecal* rabbits was found to be greater than 794 nilligmaa par kilogram sad loss than 1260 sHligrass per kilogram. ill* compound aas classed as mildly to aodsrately toxic by skin absorption is sale and faoal* rabbits. Survival tia* aas fir* to tea days. Toxic syaptoas iaeluded reduoed activity and weakness in two to three days followed by paralysis in aaiaals 43 through 46 inclusive. At autopsy there wars hssorrhagic areas in the lungs and liver hypereoia. ' GBRN002991 TOWOLDMONOOQ2073