Document 82RKq3VbweLnxy7695ywv3eOZ

.318 Olive Street Younger Laboratories ST. LOUIS I, MISSOURI Genii^iccde Ana1lqtiiRiacb&tUiti . . . Pha^macalacfUil. . . Anal-fsli Office Phone: CHestnut 1*4382 Residence Phone: ULrich 2-8683 Auvjuot 3rd, 1.66 LUBJvXT - Toxi colofjioal Investigation Of i y ;.raul AC (00-67). ilonoanto damplo No. 134 - 7-776 Monsanto Krojeot No, 7-66-40 t^t ;x;n - Monsanto Chemical Company, ut, Louis, Bidoouri, ibhhhQh.iNTAL IHOCZJXJRK - \) Oral LD^q In ttato , Undiluted fydraul AO was introduced in albino rats oy nouns of a rubber cat!3 After the approximate Minimum jiethal at levole designed to bl calculation of the LO^* Obsoi'vati^ns fi ooloct^d oniiaa^d>ft,&!3 thi The data are of B^e)juo*Dawlcy strain a hypoooWc cyrinsc. groups ofrato wore fod t oraby supplying data for toxicity and the vlscore of d nacroacopically. B) The Minimum Undiluted white rabbits For Ilnbbits 'od by stomach tube in varying amounts to New Zealand find the lethal rqngo. Observations were made for outward syraptoias of toxioity and tho viacara of those animals that succumbed was oxaninoa raacroscopically, Tho data are shovn In Table 11, C) Toxicity By akin Absorption In babbits Undiluted Pydroul AC was applied in varying Aaounto to the clo.oly clipped, intaot skin of New Zealand white rabbits and the treated areas covered with plastic shields, A leather collar was placed around the neck of each rabbit to prevont them from turning their head sufficiently to get at the application. Observations wore made for outward evidence of toxioity and theviaoara of :11 unimala that cucounbod tvas examined acrosoopioally. The data ore found in Table III. Thi* confidential report ie not to be ueed in any form of advertising without written permianon 0621066 TOXSTUDIES0413 To*, Konaanto Ohomical Col ly, bt, Louia, Mi.^uouri Toungor laboratories Certificate of Analysis - Page 2 (3-3-56) AXPLuIMiflTAL rROCi)LURE - (Continued) D) ol-cin Irritation In Aabbita Undiluted Pydraul AC rvao allied to tho closely clipped, intuot of tiiroo albino rabbits and observations ;.uide 0vor a -period of several days for irritation. IIjo reoulto, baood on the scoring technique of Rrolsa, ..oodord cuid Oalvory (J. of fharra. & hxp, Therapeutics, Vol. 02, Ho* 4 (Aoc,) 1944), arc yiven ir Table IV. ' -0 4yo Irritation In Rabbits 0.1 Mili.ilitap of undiluted :';/di*aul . was placed in tic* conjunctival aac of the right ;.-ye of each, of t.u-Ou* albino rabbits raid Lae re.suiting irritation scored according to Lraizo, .oodard :;jid Calvory (J. of rhana. & .bey, Thora.-outico, Vol, 82, No. 4 (Too,) 1944), Lata from aovoral days observation are shown 1a Table V. F) Vapor Lihalatlon In Rata Four mature nolo rats wore , iaood in a metal chamber of 25 litoru capacity and oxpoood for six houro to an atrnos: here of rydrnul AC vapors produced by aspirating tho li.uid at room tenporature The sample was poured into a throe hole, round bottom floak and cc3ipr;.:30d air passed over an orifice, the lower end of which was iaa.arood in tho liquid, A glass tuba lad from the flask into tho chamber. A glass inpinger was placed in tho lino to brook up droplets and allow, as nearly as practicable, only vapors to pass. Air prossure averaged about 44 pounds ixjr square inch. Tho nui:nolo ware oboorvod for toxio -jyiLptoraa, aid, jince there wore no doatns, all were held for ten days observation. The data are shown in Table VI, YOUNGER LABORATORIES 0621057 TOXSTUDIES0414 ? 3$ ^onaanto Chamioal Con \yt lit Louis, Missouri Younger Laboratories Certificate of Analysis - -~a^-e 3 (0-3-50 T A3 l I li: OH.il 10r^ OF VYDdAUL AC {(J2 67 ) 0** ) Jim L...U1 No, - hex 1- j alo 2- Mala 3- Male 4- Foniale p- Female 6- /dale 7- Male 8- Female 9-- Male 10-- Facials 11- Facials 12- Fera&lo 13- Female 14-- Male 15- Male 16- Female 17- Female Id- Female 19- Fora&le 20- Male 21- Male ..oiil'.t urn. 260 245 275 220 210 240 255 225 290 195 210 225 200 260 280 215 205 235 245 230 2.40 Jose 5a. /Kg. 4C.0 40.0 40.0 .*0.0 40'.0 45.0 45.0 4 b *0 45.0 45.0 50.0 50.0 50,0 50.0 >0.0 55.0 55.0 55.0 55.0 55.0 53.0 Pate Survived Aurvlvod .acd Jurvivod Juxvivcd Died Jurvivod Jurvivcd Jurvivcd Died hied Survived ourvlvod 3urvivod Died Died Died Survived Died Died Jurvivcd DlJCUOdlOB Ti)0 Oral LDCyr.t was placed at 9>2,,0 jtr;raauGe 1or Ai-iillOoi^-joramm, Suurrvviivvaal til.;;oo >vvaoa ovurnilo it There ./aa covers diarrhea in oil aniinals ao might bo ox iron the high feeding levels neoeosary to obtain kills. ..oakness and lethargy of several days duration developed, There was three Instances of mocerato oscular incoordination in the survivors* The condition cleared in seven to tan days. At autopsy pulmonary congestion was the only important visceral change notod maoroocopioally. 0621058 TOXSTUDIES0415 1'ot Monsanto Chcmioal Coi ay, Jt. Louis, Missouri Younger Laboratories Certificate of Analysis .* Page 4 (0-3-56) mini um Animal Ho* - Sex 1 - Male 2 - Female 3 - Female 4 - Male 3 - little 6 - Vale ..'eight 2.0 2.5 5.0 3.2 2.5 2.0 T a 3 L 11 v3al flow of '/yjoaul ac (00-67) * ix>a aalsits TOGO Kfl* Weight Change 5 Pays Alter Jos ing Fate 2.0 5.5 4*5 5.5 7.5 10.0 - 4.0 i-5 -10.0 `j - 6.0 -14-0 i> -i2.o ;i -10.0 # Survived ..urvivod Died - 11 Days died - 6 Lays died - 11 jays Jied - d -ays jiscussion - Ths hinimua Lethal Oral Josa range was found to be 5,5 to 4o grams por kilo^T. :;i. b'urvival time was six to ,.lven Joya. All animals loot weight for several doy3 after being fed.* Those auoouKbiug continued to lose weight and became very weak before lying* There appeared to be slight paralysis* At autopsy there who livor discoloration and noderote jnilmonary hyperemia. TAfiL .3 III TOXICITY OF 'tTOittUl AC (00-67)' BY SKIN ;.3s02P?I<Mr IN .;AJ31T3 ..eight Change .'eight dose 5 Says After Animal No. - Sox K C. fl. /Kg. o 0 sing Fate 1 - Mole 2 - Mole 3 - Male 4 - Male 5 - Male 6 - Mai. 7 - Male 2.7 2.0 2.4 5.0 2.5 4.0 2.2 3.0 2.7 6.0 2.6 7.5 2.2 9.0 + 4*0 yt 0.0 - 3.0 54 - 4.0 0 - 8.0 $; - 5.0 ;1 -10.0 survived Survived Survived jiad - 21 Jays Died - 10 Joys Died - 8 Jays Jiod - 12 Jays J1SCU3SI0N - The Minimum Lethal Oooe by Skin Absorption was 4*0 to 5*0 grans per kilogram. Survival time was eight to twenty-one days and weight locsos ran from fifteen to twenty-oight ,r cent. The animals gradually lost appetite and weight. This was followed by unsteadiness and oojkj muscular incoordination, the latter becoming evident a few days before death* At autopsy no specific abnormalities were observed m&oroscoplo&lly* 0621059 TOXSTUDIES0416 i'oi Monsanto Chomioal Co i\y, Jt. Louis, Missouri Younger Laboratories Certificate of Analysis - page 5 (8-3-56) T A B L B 17 SKIM l.UlTATIGH IN RABBITS AFTER ALLIGATION OP 'PIMADL AC (OS-67)* AnInal No, - Sex 1 - Pemole 2 - Male 3 - female Avoraga Numerical Evaluation At The End Of 2 Hours 24 Hours 49 Hours 72 Hours 120 Hour, 0110 i21 1 011 1 0 0 0 0.3 1.5 1.0 0.6 0,0 DISCUSSION - One animal out of three* showed un average ccore of 0*5 out of a possible o.O. Ovemits, orytbeoa ranging from slight to fairly wall defined appoared on all tha oniuml8 for an average Maximum score of 1.3. At this time the shin was wiped free of Fydreul AC, a slight aoount of redneas with no edema was still present on two of tha animals after seventy-two hours* However, all ruoelvod. a score of zero on the fifth day. Pydroul AC was classed as a mild akin irritant. IAB1S V EYE IMITATION IN iiABBITS A5T2B APPLICATION 07 VIDRAUL AC (OS-67)1 Animal No, - Sox 1 - Male 2 - Male 3 - female Aveng, Numerioal Evaluation At Tha End Of 1 Hour 24 Hours 43 Hours 72 Hours 6200 04 2 0 0400 7.3 3.3 0.6 0.0 DISCUSSION - No immediate dieooafort of copaa^uonoe was observed upon application. The average soore after one hour was 7*5 out of a possible 110. There was moderate redness of tho palpebral coajunotivae, oonaider&blo loorimation, and slight edema. The irie and cornea were little affeoted, Laeriaation and edema praotioally disappeared ovemite. The average soore at this time woe 3. J. Two of the animals were free of inflammation In forty-eight hours .ydraul AC was classed as a mild eye irritant. 0621060 TOXSTUDIES0417 Tot Monsanto Chemical Cc any, Jt Lcuio, Miosouri Youngur Laboratories Certificate of Analysis - Fage 6 (0->-56) T A B L a VI SIX H0U:t INHALATION OF 'I'YiXiAtH. AC (OS-67) * VAF01UJ BY EATS Average .ialative Humidity XXnnao4i.dde Chamber.......... 64,0 $ Avora^po Teommpjweraattuuroe Inaido Chamboer ............ .. 76.5 JF. Animal No, - dox Fate Observations during Exposure 1 - Male 2 - Male 5 - Male 4 - Male Survived .purvivod Survived .survived :tati`er itild discomfort, no pawing at the nose. breathing about normal. jiscussioir - All aniraala eurvived tno six hours exposure as wall os the ten day observation period. The aniiaals were riot seriously affected by the vapors, Breathing remained regular and irritation was sufficient to produoe only a alight degree of laorim&tion and salivation. The -asal mucosa iron slightly redder tlian normal when the an1mla were removed from the chamber tut no edema was observed. Appetite seemed to be unaffected the day following exposure. , ,,_; -v-\ in devij'.c'jmonl fl i'j3 -.iv: .'.i'i; :.r 1 ).:>/ !.? i.-i rc-;uionil.ls aalefl comact*. Imu.'u vsvUtoUurml by theTM io advert isiug cony. Tb* source of tub material is not to be divulged until it appears in formal publications. No exceptions to the established rule may be mads without the approval of the Medical Depart ment in St. Louie.Customers' .inquiries regarding matters of toxicity are to be referred as before to the Medical Depart ment in St Louis for reply. -- Monsanto Chemical Company C62LG61 TOXSTUDIES0418 To i Monsanto Chemloal Go. ny, 3t. Louis, Missouri Younger Laboratories Certificate of Analysis - Pago 7 dUMHAkY The Oral LDr- of Pydraul AC (03-67) for rats was fount! to be 52.0 grama per kilogram* 3uoh a liigh figure indicates) tliat the compound ie practically i.-nocuouo when fed orally to rata* The Minimum Lothal Oral Dose for rabbits was 5*5 to 4.5 grama .or kilogram* The mni^w x,otlul Oooo by 3kln Absorption in rabbito was 4*0 to %Q grama per kilogram. .ikin Irritation in rabbits consisted of alight to well defined, erythocia with no odea* for an average okoximuct ucoru of 1.5 out of a possible 3.0. The compound waa oloasod as a id.Id skin irritant. The average maximum score for j$ro Irritation -.rue 7*5 out of a possible 110. It was al30 olaosed ao a mild eyo irritant. date ourrired a six hour exposure to bydxvujl ,r; vaporo 'which were found to bo only slightly irritating. 0621062 TOXSTUDIES0419