Document NEY0a2RLmVqVbjV0dMq4YLLLy

'ra n.ourT i*> j.---*p: C '" Younger Laboratories BtocA**uil:t . . Ph&tmac&loyuU . . . AnaUf^U Hf***"'**** 199 tun CAVK HOAD UAINT lAH'IH, MU, Ml** Dhonii TIlDtN 6-9940 C&itijficcde. AnaltfMi. Toxicological 1 "eatigation Ofs Hjnsanto Soaple Nnnoer M Mor.earto Project Mueber Y-P9-41 HCS 900 3TOY COMXICTEO TOR ttor. santo Codparty, at. Louis, Missouri ' Y tJ A SXFEfilKWTAL PrCCKOCRS - \ A) Oral LD^ (Rats, Mixed S-x> Th diluted compound was fad by stomach tube to Sprague-Davley strain albino Ml* and female rats. After the approximate Minimus Lethal Dose was determined, groupn of snip mo female rata were fed in increasing doses at increments o: 0.1 :r.-ictio/u,l log Intervals at four levels designed to blanket the toxicity range thereby supplying data for calculation of the LDje which-ws* dnne according to a Bonification of the method of E. u. de Beer, Observations were mace for toxic eysptoms and the viscera of the tost anissla were examined aasroncopically. The data, together with the dilution at which the cospound wan ted, are shown In Tjbla 1, B> Sxln Absorption KLD tebbits, Mixed &-x) TVe undiluted compound was applied In increasing doses at increment* of 0.2 fractional log intervals to Iho Cioaely clipped. Intact aicin of Mew r.ealxr.l whits male and ftsal- rabbits. The treated areas were covered with plastic stripe and the auiAs.a held in wooden stocks ior wriois up to twenty-four hours, after whicn time they r sasigjwd to inUviduil cageo. Observation' wer* ssl* for toxic sysptoms and th* viscera o: the teat sfumnls w*re tiniini"i sacro" -gplcally. Trie -i-iUi ire ohowr ui T'.bie 11. i TOXSTUDIES0789 */ To: Monsanto Company St. Lou in, Missouri YourRr labors boric? Certificate of Annlyn . - Page 2 15/VGy. - Y-09-**X EXPERIMENTAL 1-kOfiiClrtJRE - (Continued) C) fikin Irritation (Rabbits, Mixed ScO The undiluted compound vnn ppliM'to tn-j c.irped, intact akin of .ilbiw male and female rabbits and removed after twe:ity four hours. The application covered with olastie strips to retard evaporation ir.d avoid jontosirijti.ru Observation? were made over - period of several day? for irritation, ftle date, scored according to the method of Draire, koodard and Cal very i,Journal of Phare, end Sxp. Therapeutics, Volume d2, December, nr'- shown in Table ill. D) bye Irritation \Rabbits, Mixed Jex) . 0.1 Milliliter of undiluted sample was placed in the conjunctiva] aae of the right eye of racn df three s.oino ma.e and female rabbits and observations aide over a period of several days for inflamation. The eyes ware rinsed with wars isotonic saline solution after twenty-four hours. Vapor inhalation iHale Rite) Six mature sale rats were placed in o metal chamber of fO litvrn ;apa:ity .and exposed for six hours to a concentrated atraospnere of eopora produced oy pae.'.lrr a stream of air through 204 gramr of the compound contained in a .iOC-mii. ililer erlenmoyer flask. . * Vapors from the flask passed into h one liter bottle to remove droplets and then into the chamoer. Air flow through the sample was four liters per minute as measured by a calibrated rotameter. This wan sufficient to violently agitate the liouio. Mo supplementary air was introduced inasmuch as the above supply was a*i>le for the animals owyeei requirements. The animals were observed for behavior and since there were no deaths, ill were held for ten days observation, then cacrifieen for macroscopic examination. The data are shown in Table V. SUMMARY HC S_ 900 ' A) Oral U>90 CHata, Mixed :i The Oral LD,o tr *!*> n(1 (vile nts was placed at 1230 milligram* oer i with lower and upper limiti f lido to 1J&0 milligrams per kilogram. i mi.dly toxic oy oral in^ntion in : * mmap*W'v m-W">1 ,K . To: Konnanto Coapaay St. Louis, Missouri rounder Labor* tcrieii lertificat* of Analyeis - fitg* J Ot/i/69} - SUMMARY - (.Continued) B; Skin Absorption MLD ^Ksubita, M.xed .tex) The highest application oi '/'M ailligraas par Kilbgraa wjo found to br non-lethi: by skin aoaorctJon ir. <*aU- md resale raDbit;.. The coopound was eain*d an pra.-ticiHy non-toxic by okin absorption in ttil* 11J female rncoite. '. Ci Skin Irritation \kiboite, Mixed Sex) ftt* compound wan classed as n ild irritant when applied undiluted to intact akinof rule and femalerabbits. The average maximum score was 2.0 out of possible 8 in twenty~four hours. D) Eye Irritation (Rabbits, MixedSex) The compound waa classed is a slight ays irritant in aals and teenls rabbltiu The average aaxiaus scor-.' wno 10.6 out of a possible 110 in one hour. ' ti; Vapor Inhalation (Hale Kits) All animals survives the six hour exposure as well as the following ten day observation period. ' It was concluded ait the vapors -ere practically non-toxic um.tr conditions of the test. ' ' ^ .. . ' ; ic N j. ; yODHQER LABORATORIES !1 $ I TOXSTUDIES0791 r^wmm wWwppppfWfjlwiii mu imp %i<wwgyf* '.'w.my M' mi -- - - '. .',. : .T:............... . z&aaa . MiaM^ri nil- -i i < iniirftf'AtAr'^M Tbl Monsanto Coapany St, Leuia, Missouri Iou{r UU>rtorli Csrtifleate of Analysis - Page 3 (5A/69) - T-^9-%1 SUWUBT - (Continued) ) Skin Absorption KLD (Babbits, Mixed Ser) Tbs highest application of 79*0 ailligraae par kllogrsa was found to be noa-lethsl by ikln absorption in aals and fenale rabbits. The compound vas classed as practically non-toxic by Okie absorption in nale and feaale rabbita. C) Skin Irritation (Babbits, Mined Sex) The compound was classed as a slid irritant when applied undiluted to Intact ekla of sale and fcaale rabbits. The average auiaua score was 2,0 out of a possible 8 la tventy-four boors. D) Eye Irritation (Babbits, Mixed Sex) Tbs cospound vas classed as s slight eye irritant in sals and fsnala rabbi.*. The average aaxiata score mi 10,6 out of a possible 110 In ooa hour, S) Vapor Inhalation (Male Beta) All ti--! survived the six boor exposure as veil as tba following ten day observation period. It vas concluded that the vapors were practically non-toxle under conditions of ths test. TOOMSB LABORATORIES Ml MB.VUI D. B1HC8 W's 036*25* TOXSTUDIES0792 TotH&aoaato Coupeny .. .............. . , .. , St. Leuit. Mleseurl '" Inwgtr Laborutoriea Certificate af Analytic Page 4 (S/9/69) T-69-A1 T A B 1> I I THE ORAL LDe OF *HCS 900' F08 RATS Sasple Fed As A 1D.Q* Solution la Cora Oil tool No. . Sax Weight Os . Dote Fate 1. fault 2- Male 3- Fastla A- Mala S- Fault 6- Kale ?. Fault 8- Mala 9- Fault 10- Halo U. Fault 12- Kale IV Fault IV Mela IV Fault 16- Halt 1?. Fault 1&. Kale IV Fault 20- Malt 225 2*5 210 250 220 260 250 455 235 2*5 220 250 250 2*3 220 250 225 2*0 225 Z60 79* 79* 79* 79* 79* 1000 1000 1000 1000 1000 1260 1260 1260 1260 1260 1580 1580 1580 1580 u&> Survived Survived Sortited Survived Survived Pied Survived Survived Survived Survleud Died Died Survived Survived Died Died Died Survived Died Wad fbt Oral LDS0 tor ule tad fault rata u plated at 1280 ullllgr-- per kilograu with. lover and upper Uaite of 1180 to 1380 uUligrese par kllofraa. The eupoud u claeeed u silAljr toxic by oral Lngtetiea 1b tala sad feula rata. fax-rival tiaa us m to three d*/a with seat deaths occurring Aurics the uooad fey. foxia eyupteu laelufed ndufl appetite for two to three days, increasing wi collapse. At autopay tharo woo Jaundice araaa of tha lirar, Ions hypertalo. tad dleteuded coronarUa. Surviving aalula vara sacrificed aim daya aftor feeing. Haarooaoplc examination bowed diacolorei orate of tfeo llv*r and l<u* hyperente at tha higher feugo levelai discoloration of tha livar was noted at the lover doosga lavale. TOXSTUDIES0793 ' Tat MomaaU Coapaajr . St, louia, HlMaurl ' to*f*r laboraUrlaa Ctrtifleata of Analyaia - P*c* 5 (VV&9) - T-69-A1 mu n St HSSURIM LBT&A1* C08t OP 'MCI 900' H SKID ABSORPTION IN RABBITS tt1- Appllad 9*4listed data*!**.- 3* Haight -iJU- Odm SfcZHk tf*l|ht Ch*i* 5 Bay* Latar _____ J{._____ 1. teaal* 2 - Mala 3 . ratal* 9 tala 5 - ratal* 2.9 2000 2.9 3160 2.3 5010 2.2 79W> 2.9 . 7990 0.1 0.0 . 0.1 . 0.2 - 0.1 Fata Suninl Iwlni Soniwd twvlMd srvlv*4 DISCUSSION - . Tb* klctaat .pplicatioa of ?9M> aUlicraaa par kHocraa * found to b* soa~ltHi 9y tala abaorptioa la tala ad faaaia rataita. . Dm aoapooad vaa oltatart m praatteally aoo-toxlc bj akia abaorptlao In aaia and faaaia rabbit*. . Stale ayaptoao laoladaA raduead appatlta and alight la aolatla #3 'ttriiilt I9t wight laaa la foertaa* day* vu 0.5 kilofrat to 0.? kilogroa. Imirtat animl* vara aaerlfleod foortoao day* afitr tesla*. Maeroacaple ojraalaatiao tketmi mettlet eat iiaeeleret lir*rf *d aaaooua InUftiMi Is aataala #9 ad 19* Anw af alight dlaeoloratioa or th* Uvar war* notad la tslmlt 22 eat #5* *h# rtsetr* at aalaal #1 appaarad tonal. --1fMi 03642.1 TOXSTUDIES0794 TOXSTUDIES0795 i. fat NtMWU COfMJ . St, Uli, HLaaowri lMA|ir hbontrlu Crtideit of Aaalyal# . hfi ? (WW) T>jMl run nr EI K llUITAtlON IK RABBITS mu APPLICATION OP `MCE 900' Saspla (0,1 Hllliliitr) Appllad Undliutad Nuaarical Evaluation At lb* End Of Aniaalllo* - Sax 1 Hour 24 Hour# 46 Hour* 72 Hour* 120 Hoar* 1 - Hal* 1 - Panal* 3 , ha*b Avar*|* 10 10 u 10.6 0 0.0 DISCUSSION lfa* soopound was elaaaad n a alight apt Irritant 1b aala and faaala rabbits, fha awarag# miaua *cor* u 10.6 out of a poaslbl* 110 la ana Hour, Avar* awa Ud to aodarwl* dlaceafort with blinking and cloasd Lida iaaadiattly fallowing application. ditblB tai ainutaa thar* waa alight srytbaaa and ttea, asd diacharga. At th# m hour reading aryttaert was elicit, adeaa alld, aad thar* waa ar-darat# diacharga with traeaa of wbltiah exudate. 1W* m no eoraaal clowdinaa*. Vitkin twenty-four hours discharge had eaaaad and arytbaaa and adaan war* slight Vithis forty-eight hour* thar* waa barely perceptible arythaaai adaan had disappeared. All aalaala racalvad a aeoro of saro within thro* days. .. . ***IW!1 Wl* PUWHMIlgW . *** TOXSTUDIES0796 lUHrti Tpl NoAMBtO CoapeitJ 0k. Louie, Missouri Younger laboratories Certificate of Aaelyals Page 6 (5/3/19) - Y-49-41 run INHALATION Of *HCS 900' VAPORS BY RATS Arerax# T*apritri Inilti Choaber Average Relative Hualdlty IMldo Chaaber 74* P* 54 * Aaount of Saapl* -- To atart 204.0 Qn Recovered ...........................202.9 Oraai Vaporised or left to equlpaeat .......... 1.1 Ormaa (O.JAS) Atlai Wo.. Sex fete Observation Pariag_t*poeurert__t 1 . Male I3 (tall k - Male I I Hal Survived tori"! Survived tori"! No iaaediete effect ... " lltoo ... N wikMii or uni discharge ... "~1 'PU'.tloo. - DISCUSSION - .. ill Ataals nrvivad the six hour exposure a* well as the fellovlAg tea top . observation period. , It wee eoeclnded that tho vapors were practically Ukteilc under condition of the test. ,' There were a visible sipie of weakness or distress of any coneetueace observed dories the exposure period. Oeal*r eed eaeel aueoeee itwlmd frea of ioftaa--tloe. qm tea day obeanretioa period wee unevefltfhl. Weight fata wee waal. teat ealaals were neriftead tea deya after exposure. Maerosoeple euainatln rewealed alight aawea t>i lues oeageetloa la all aniaelai otherwise the viscera appeared norasl. .- 1 JEW wygwffaf jmw&w |P TOXSTUDIES0797