Document gb1bEKZ0DzavRa5gwN3DVKqYJ

wc.--N0jjgSE6ia'/ REP3RIF115. -- Younger Laboratories QiaoktmUii .., PkatonocoloqUU ... AnaLfili 1M CLIFF CAVI ROAD Saint Louis, mo,, asiss PHONSl TlLDBM 6*9640 Gefitifacate oj Analyiti SUBJBCT Toxiaalafieal InTaatigation Of: MCS - 40 4 Haaauta Saapla Busbar 24$ Nanaaato Project Mabir f-45-214 JUU17 12th, 1966 MOOT CONDOCXD FOB It*muto Cupaay, St. Louis, Missouri BPBINBRAL PBOCBXJB* - 4) Oral LC,0 (Bat*, Mia*4 Sax) lh* uadilutad aoapauad au fad by atoaaeh tub* to Spragua-Dawlty atnla alblao aal* and fault rata. After th* approxlut* Mlalua Lethal Dm aaa dataralaad, (roups of ul* aid faaal* rata aara fad la iaeraulag doaaa at iaeraaaata of 0.1 fiastloaal las lataraala at four 1avals dasisaad t* blaakat th* texieity raas* tharaby supplyiag data for mlaulatioa of th* LD,0 ahlah aaa doa* aecardlag to a aodlflsatloa af th* aathod of I. J. da Baar. Obaarratlou aara aad* for toxic ayaptou ud th* Tiaoara of th* aalula that asocuabad aara axaaiaad ucroaaapioally. Ik* data ara ahon la Tabla I. B) Oral MLD (Babbita, Mixad Sax) fh* aadllatad ooapaund aaa fad la laermalag doaaa at iaeraaaata af 0.2 fiastloaal lag lataraala by atoaaeh tub* to Ha* Zaaland ahlt* ul* aad faula rabbits. Obaanratloaa aara aad* for toxic ayaptou ud th* vise ara of th* aalula that aueeuabsd aara axaaiaad uaroseapieally. A* data ara ahou la tabla II. HONS 03S056 To i Monsanto Cenpanp St. Louis, Missouri Touagwr Laboratories Certificate of Analysis - Paga 2 (1/12/66) - 7-65-214 EXPERIMENTAL PBOCIDUBE - (Continued) C) Ucla Absorption MID (Babbits, Nlxsd Sax) Iks nadllatsd eoapaund saa appliad in lneraaslag doass at iaeraaaata of 0.2 fraatlonal lag intervals to tbs slssslj ellppsd. Intact akin of Mss Zealand sblta oala and facial a rabbits. Tbs trsatsd areas acre covered with plastic atripa and the aniaals placed la wooden stooka for periods up to tsentp-four hours, after which tlaa thep wars assigned to Individual cages. Observations wars aads for toxic spaptoas and the viscera of the aniaals that sussuabsd wore axaainsd aasroseopisallp. Tbs data arc ahown la Table III. D) Skin Irritation (Babbits, Mixed Sax) The undiluted eoapaund was applied to the clipped, intact akin of sale aad faaale albino rabbits aad raaioved after twenty*-four hours. The application was covered with plastic strips to retard evaporation aad avoid eoataadratioa. Observations were aads over a period of several daps far irritation. The data, scored according to the aethod of Draiso, Soodard aad Calvarp (Journal of Phans, and Sap. Therapeutics, Yeluee 82, Deosaber, 1944) are ahown la Table IT. I) Bps irritation (Babbits, Nlxsd Sex) 0.1 Milliliter of undiluted saaple was placed in the conjunctival ass of tha right ape of each of three albino nbbits and observations node ever a period of several daps for laflsanation. Tha apes sere rinsed with warn isotonic saline solution after tweat^fsnr hours. The data, scored according to the nethod of Drains, at al, are shews in Table T. P) Taper Inhalation (Hale Bata) JPeur nature aale rats were placed in a natal ehanber ef 33 liters eapeeitp aad exposed for six hours to a concentrated atnosphere of vapors produced bp passing a streaa of air through 100 m11111tars of the eoapaund contained ia a JOO-niHiliter Erlenaeper flank. Tapers fron the flask passed into a one liter bottle to renews droplets aad then into the ehanber. Air flee through the saaple was five liters per slants as neasured bp a cali brated rotaaetsr. This was sufficient to violentlp agitate the liquid. MS supplenaatarp air was introduced 1nonsuch so the above supplp was aaple for the aniaals expgea requireaenta. The aniaals were observed for behavior sad, since there were no deaths, all ware held for tea daps observation. The data are shown ia Table TI> MONS 038057 Toi Monsanto Csapanp St. Louis, Missouri Younger Laboratories Certificate of Analysis - Pag* 3 (1/12/66) - T-6J-Z14 gDHMABX - A) Oral LC,e (hats, Mixed flax) The Oral LD,e for aala and fsaals rata saa placed at 19,800 silligroaa par kllagraa with lawor and upper Halts of 17,0% to 2},165 allligraas par kllscraa. Thw aoapound was classed as practically ace-toxic bp oral ingwatioa ia aala aad feasla rata. 1) Oral NLP (Babbits, Mixad gax) IMe Mialaaa Lethal Oral Doss for aala and faanle rabbits aaa found to bs traatar than 1580 ailllgraaa par kllagraa aad lass thaa 2510 r1111grras par kllagraa. Iks csapouad aaa slaasad as slightly toxic bp oral ingestion la aala aad fsaals rabbits. C) Skla Absorption NLD (Babbits, Mlxsd gax) lbs Mininun Lethal BaaB bp Skis Absarptlda la aala aad fsaals rabbits was found to ba grantor than 1000 allligraas par kilsgraa tad lass than 150 allligraas par kllagraa. Tbs oaapauad saa classed as alldip toxic bp skla absorption la aala and fasuls rabbits. D) Skin Irrltatlaa (Babbits, Mlxsd gax) tbs saapoaad ass slaasad ss a slight akin irritant aba appllsd aadilatsd to iatast skla of aala aad fsaals rabbits. The awarags aarl.ana seora arts 0.6 oat of a passible 8 ia twentyfour hears. B) Bps Irritation (Bnbbits, Mixed gax) Tbs eoapsoad was classed ss a slight ops irritant in aula and fsaals rabbits. The awarags nations score was 11.6 out of a possible 110 in oaa hoar. T) Vapor Inhalation (Mala Bats) All aalaala ourrlwad the six hour exposure ss sail as tha following tea dap abaarwatlea period. It aas eoneladed that the Tapers ware relatlwalp sou-toxic uadsr eoadltieaa af tha test. TOTKQEB LABOBATOHIBS 'Lj-f BT: IBED N. TOOMOm J' MONS 038058 (I Honaaato Ceapaap St. Louie, Missouri Touager Lsberuteries certificate of inalpala - Pag* 4 (X/12/6&) - r-65-214 tint 1 THE OBAI 12),, Or 'KCS- 404' FOB UTS Susple Tad Undiluted (lael_5o._-_jax 1- rsaala 2- Hale 3- naali 4- Hals 5- resale 6- Hale 7- rsaala 8- Hale 9- rsaala 10- Mala 11- rsaala 12- Hale 13- resale 14- Mala IV rsaala 16- Hale 17- rsaala 18- Mala 19- rsaala 20- Mala leight -Sju_ 230 245 220 240 225 250 235 260 240 265 235 255 225 250 230 270 235 255 240 260 Dssa 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 ___ an. Survived Survived Survived Survived Survived Survived Survived Survived Died Survived Died Survived Died Died Survived Died Died Survived Died Died DISCUSSION - The Oral U>.0 for sale aad faaale rots aa placed at 19,800 eilligrsa* per hllograa with laaar aad appor Halta of 17,030 to 23,165 uilligraaa par hilegraa. Tha aoapoaad oaa claaaad as practically moo-toxic by oral iageatlaa la aals aad faaala rata. Sarrival tlae oaa sararal hoars ta four daps with aost deaths oeeurrlag la three to four daps. Texio apaptoaa iaeludad earare diarrhea, loss of appetite, aad iaoreaaiaf saahaaaa. it autopsp tha gaatroiateatiaal tract aas gaseeua aad there aas liver eoageatioa- . MOMS 038059 Toi Monaanto Coapany St. Louia, Hiasouri lounger Laboratoriea Ce'rtifioate of Analyaia - Paga 5 (l/12/b6) - r-65-214 TABLE II TEE KMIMm LETHAL ORAL D06E OF 'MGS- 404' FOR RABBITS Saaple Fad Undiluted |niaal_jlo._;_Sax 1 - Faaala 2 - Mala 5 - Faaala 4 - Mala 5 - Faaala 6 - Male eight JA:. 2.3 2.4 2.6 3.1 2.7 2-7 Deaa SfcilSfc 1000 1580 2510 2510 3980 6310 Weight change 5 Daya Later ...Hi 0.2 0.1 - 0.2 - 0.3 - 0.2 - 0.3 ----------- IS*!._____ Surriaad Survived Died -- 5 Daya Died -- 7 Daya Died -- Daya Died -- 8 Day* DI8CUSSI0II - Tha Hiniaua Lattaal Oral Doaa for aala and faaala rabbita ai found to ba graatar than 1580 allllgraaa par kilograa and loan than 2510 allligraas par kilegraa. Tha aoapound aaa olaaaad aa slightly tozle by oral lngaation la aala and faaala rabbita- Survival tiaa aaa flaa to alght days. Ibaia ayapteaa included gradual loaa of appatita with iaeraaaiag aaaknoaa, lethargy, and eollapae. At autopay thara aaa renal, liver, and pulaoaary hyparaaia by aaoroaeopio eventnation. The jpcterlal in this report ' itobtu-"! in dovnlcpmont of the 7rev''.'.tic";! riir.y ,.- in,j''...:-. , , v .1 hi,;.it b r,-` to i'."' ' ' / t '.! or-tarts, n, 9 i*-. , e ' i' t .i: r, ' ' ' .' - 1 r. n;; ' toxici.v tii-a t> i -.:~ . . . 1mant jo St. Louis 10L' . ' ' ............... . r -J l.~ L-. a. ,-f Momonto CViemi-tl Cci-t-ry HONS 03060 Tot Nonaanto Conpany St. Louia, Mlaaourl Touagar Laboratorive Certificate of Analyais - Paga 6 (l/l^/6b) - y-6^-214 imi in THI WNDTOH LETHAL DOS! Of 'MCS- 404' BT SKIN ABSOHPTICE IN IASBIZS Saapla Appliad Dndilutad Aaissklss-i-S" 1 - faaala 2 - Mala 3 - faaala 4 - Hnla 5 - faaala 6 - Mala alght 2.T 3-3 2.5 2.6 2.3 2.8 Daaa Bfc/Jte 631 1000 1580 2510 3980 6310 alght Chaaga 5 Day a Latar _____ sti_____ 0.1 - 0.1 - 0.2 - 0.4 - 0.2 - 0.3 --------- fti*______ Sarvivad Survlvad Dlad -- 6 Days Olad -- 9 Daya Dlad - 14 Daya Dlad -- 5 Daya DISCUSSION - lha MlalaUB Lathal Dona by Skis Abaorptioa In aala and faaala rabbita aaa fauad ta ba graatar than 1000 nllllgraaa par kilograa and laaa than 1580 nllligrana par kilagraa. tba aoaponad aaa alaaaad aa alldly tozlo by akin abaorptloa la aala and faaala rabbita. Survival tlaa aaa flva ta fourtaan daya. Taxlo aynptaaa lneludad aaaknaaa aftar thraa to alx daya, raduead appatlta, dyapaaa, aallapaa, and paralyala. At aatopay tbara aaa pnlaoaary hyparanlaj otharaiaa no vlacaral ahaagaa of toaaaquaaaa aara aotad. HONS 018061 Tei Noaaanto Coapanjr St. Louis, Missouri Touagsr Laborstorios Csrtificats of Analysis - psgs 7 (1/12/66) - t-6>-214 inn it sum iurancR nr babbits Aran appucatic* or 'ncs- 404' gsspls Appliod Usdilutsd 4sisal_l0. Hsasriaal Ursluatios At ths Bd Of U2S 24 Hours 40 Hours 72 Hoars 120 lours 1 - Msls 2 - Tsssls J - Msls Arorago 01 1 0 00 0 0 01 0 0 0.0 o6 0.3 0.0 0 0 0 0.0 Discussion - Ths saaposad sas slasssd as a slight akin irritant shsn applisd uadllutod to intmst skis sf sals sad faaal* rabbits. Ths BTsrsgs analana ssort sas 0*6 out of a posslbla S is tMaty-four hours. Ms akin ehaagss wars aotsd at ths sad of ess hour. Orsrnight thsrs sort tss iastansss of vary slight rsdnsss with so sdsoa for sn sssrugs aoors of o.6> Hthla saranty-tso hours all aalaals wars froo of inflaooatlon. HONS 03808* Toi Monsanto Company St. Louis, Missouri lounger Lsborstoriss Certificate of Analysis - Page 8 (1/12/66) - y-6^-214 tmi t at IMITATION IN BABBITS ARIB APPLICATION 0T 'MCS-404' gaaple (0*1 Milliliter) Applied Undiluted 4Si9!i-B2f-I.8!5 1 - resale 2 - Male 3 - resale iJfeur U U 13 Runerleal Iraluatioa At The fed Of 24.ISSI* jSJSSiS JLfeSSS i2S.9SSS! 942 620 844 0 0 0 Average 11.6 7.6 3.3 2.0 0*0 DI3CUSSIQN The sonpeuad eaa elaeaed as a alight eye Irritant. The average aaxiaua score saa 11*6 out of a passible 110 la one hoar. there sas blinking but no paving at the eyes following application. Mild discharge, slight redness, very slight odeaa, and alight corneal dullness sas resorded after one hour. Hess and dlssharge disappeared overnight. lthla three days only a trace to slight erythese remained on tvs aaiaals. 038063 HONS Toi Hoaaaato Caapaay St. Loul, MlMouri leuagar Laboratory** Cartlfieat* of Aaalysis - Pag* 9 (1/12/66) - 1-69.214 mu ti IRHAIATIOH or 'HCS- 604' TAPGHS BT UTS Ararag* Taaparator# Iaalda Chaabar .......................................................... 74* y. Arango Solatia* Huaidity Iaalda Ghaabar .............................................. 44 % Aaauat #f Saaple -- To atart............................. Becorerad............................ Vapariaad or loft la oqulpaaat...................... 100.0 ao 99.} a* 0.5 00 (0.5W Aalaal Ho. - Sox 1 - Halo 2 - Halo 3 - Hals A - Halo ____ ft**.. Sarrired Surrirad Surrlrad Surrirad yboorratloao Paring yxpoour* Ho laaedlate offoat ... Lethargy altar oaa hoar . Ho diaooafert ... Horaal raaplratlom ... Discussion - All aalaal* oorrirod th* ala hoar acpoaur* a* wall aa tha follssiag tarn day ahaorratloa parlod. It oao ooaelodad that th* rapan aar* rolatiroly aoa-taxia aadar eoadltloaa of tha tost. 'With tha oaeaptioa of aodarata lathargy, tha aalaalo aho**d ao roaotioa to tha rapan. taakaaoa aas abaoat aad ao aaaal or ocular laf1 aaaatloa oaa aotod. Aatlrlty aad appearanoa war* aoraal tha day follaalag axpaaur* aad a* respiratory eoaplioatioaa dsaslspad darlag tha taa day ahaorratloa parlod. MONS 038064