Document 91eewK95gBkERRb6RvQobevjR

\ Younger Laboratories HioclmmUti. . . Phtvmacnlexfiih. . . /btaly&U Route 9 -- Box 28) ST. LOUIS 23. MISSOURI Pmmoni TIloen 6-2540 SUBJECT - Toxicological Investigation Of: Hydraulic Fluid OS-81 - Moneanto Saaple Bo. 1 Hydraulic Fluid 03-8} - Bonaanto Saaple Bo. 2 Monsanto Project Bo. T-57-1 February 26th, 1957 The data are found in Table III and Table IT. C) Skin Irritation In Babbits Undiluted saaple sas applied to the closely clipped, intact akin of albino rabbits and observations aada over a period of several days for irritation. The results, baaed on the scoring technique of Braize, Woodard and Calvary (J. of Phara. and Exp. Therapeutics, Tol, 82, Ho. 4, Dec. 1944), are shorn in Table T and Table 71. D) Ey Irritation In Babbita 0.1 1H. of undiluted saaple use placed in the conjunctival aao of the right eye of each of three albino rabbits and the degree of Irritation soored according to the aetbod of Braize, Woodard and Calvary (J. of Phara. and Exp. Thernoeutiea, Tol. 62, Bo. 4, Deo. 1944). ` The data are found in Table TH and Table TUI. This rnwfcii--h.l npst ii set to ba ued ia aajr Ion mi adwHwpg withe HONS 046338 'To: ttoaaanta Chealoal %bapany, < St. Louis, Missouri lounger Laboratories Certificate of Analysis - Page 2 (2/2S/57) EXPIKOOUL PBCCEJOBI - (Continued) E) Tapor Inhalation In Eats Pour matura aala rata vara placad in a natal chaabar of ipproximately 50 litara capacity and axpcaad for alx hours to an atooaphara of hydraulic fluid vapora produoad bp aspirating tha compound at rooa taoparatura. Tha liquid saa pourad , into a thrav hoi*, round bottom flask and compraasad air pasasd orer an orlfica, ' - the lovar and of which was lnmarsad in tha liquid. 1 glass tuba lad from tha - ' flask Into tha chaabar. 1 glass iapingar was placad in tha lina to braak up J ijr droplats and allow, as nearly as practicable, only vapors to pass. "*j The animals vara observed for behavior and, since there vara no deaths, all rata '"si. vara held for two waaks additional observation. Tha data ara shown In Table IX and Table X. HONS 036339 , 101 mowiw Mnaimi <v.-ipan7, St. Ionia, Missouri f lounger Laboretorlee Certificate of Analysis - Pago 3 (2/26/57) TABLE I THE ORAL LD,, OP 'HTDRAULIC FLUID OS-81' FOR RATS imal Ho. - Sez X- Female 2- Female 5- Hale 4- Female 5- Hale 6- Hale 7- female 8- Female 9- Female 10- Hale 11- Mala 12- Femalo 13- Female 14- Female 15- Male 16- Hale 17- Female 18- Halo 19- Female 20- Female 21- Male 22- Female Height Cm. 240 210 2J5 210 225 245 215 200 220 250 210 190 195 215 230 255 200 240 195 205 235 215 Dose Gm. / Kg. 6.00 6.00 6.00 6.00 6.00 7.50 7.50 7.50 7.50 7.50 7.50 8.25 8.25 8.25 8.25 8.25 8.25 9.00 9.00 9.00 9.00 9.00 Hate Survived Died Survived Survived Survived Died Survived Survived Survived Died Survived Died Survived Survived Survived Died Survived Died Died Survived Survived Died DISCUSSIQU - TllO Oral LD,, was found to bo 8.60 grans per kilogram with fiducial limits of 8.12 to 9.03 grama par kilogram. Survival tins was overnite to four days. Thera was diarrhaa, irritability, and nervousness observed. Some survivors lost as much as 30^ of their starting weight before regaining normal appetite. At autopsy there was liver damage, moderate kidney congestion, and gastrointestinal inflammation. HONS 036340  To: Honsinto Chemical Company, ' St. Louis, Missouri lounger laboratories Certificate of Analysis - rage 4 (2/26/37) TABLE U THE 03AL LD,- 0? 'HiDdAOUC FLUID OS-33' 7 FOa 2AIS Lnal Ho. - Sex 1- Female 2- Female 3- Female 4- Hale 5- Hale 6- Female 7- Female 8- Female 9- Hale 10- Hale 11- Female 12- Female 13- Male 14- Female 15- Female 16- Female 17- Male 18- Male 19- Female 2<^ Female 21- Female Weight Gd. 210 220 205 240 210 195 205 215 230 250 190 200 225 185 195 215 240 255 230 210 205 Doaa On. /Kg. 27.5 27.5 27.5 27.5 27.5 30.0 30.0 30 JD 30.0 30.0 35-0 35.0 35.0 35.0 35.0 55.0 40.0 40.0 40.0 40.0 40.0 Fate SurrlTed Survived Died Survived Survived Died Survired Survived Died Survived Survived Died Died Survived Bled Survived Died Survived Died Clad Died DISCDSSI01 - Th Oral LD,, waa plaoad at 34.3 grams per kilogram with lower and upper liaite of 32.6 to 30.5 grams per kilograa. Survival tine wae two to seven days. Severe diarrhea, trembling, irritability, and lethargy developed. Weight losses ran to 25j of starting weight. At autopsy the stomach was gaseous and Irritated. The liver was discolored and hyperemia. There was also pulmonary congestion. MQNS 036341 'Tot Uonsanto ChenInal Coapur, * St. Louis, Blaaouri lounger laboratories Cartifioate of Analysis - Page 5 (2/26/57) TABLE III THE BEII2CIB LETHAL OHAL LOSE OP 'HYDRAULIC PLOIL OS-81' FOB BABBITS HO* - SOX 1 - Bale 2 . Female 5 - Bala 4 - Bala 5 - Bale 6 - Female 7 - Female 8 - Bala 9 - Bala Weight Kg. 2.8 1.9 1.9 2.5 2.1 1.8 1.8 2.5 2.3 Dose Co./Kg. 0.25 0.35 0.50 0.75 1.00 1.50 2.00 3.00 5.00 Weight Change 4 Days After DO S*ng 0.0 10.0 i. -15.0 -10.0 / -15.0 i. -12.0 i. -20.0 $ -18.0 1* -15.0 i. Fate Survived Survived Died--4 Days Died--4 Daps Died--7 Days Died--4 Daps Died--5 Daps Died--5 Daps Died--5 Days DISCU3SIQH - Tha Lethal Soaa was in tha range of 0.55 to 0.50 gram par kilogram. Survival tins was four to asvan daps. Tha animals gradually became weak fro* loss of appatits. Thara appaarsd to bs partial paralysis aftar two to throe daps. At autopsp liwar and splaan wars congested. There appeared to be blood changsa. TABLE IT the unmnni lethal obal loss op 'hydraulic fluid os-85* FOB BABBITS tnlnel Do. - SSX 1 - Bale 2 - Female 3 - Bale 4 - Female 5 - Bale 6 - Bale Weight Kg . 2.6 2.1 2.4 1.9 2.4 2.2 Dose Go. / Kg. 2.25 3.00 3.50 4.25 5.00 6.50 Height Change 4 Daps After Dosing 0.0 + 4.0 0.0 fl - 8.0 -13.0 Ji -10.0 "4 Fate Survived Survived Survived Survived Died--5 Daps Died--6 Daps Discussion - The Htnliua Lethal Dose was 4.25 to 5.00 grams per kilogram. Survival tine was five to alz daps. Weight losses resulted from poor appetite. Animals Ho. 5 and Ho. 6 gradually became lethargic but did not appear to develop paralysis. At autopsy kidnaps, liver, and lungs ware all hppareaic. MONS 036342 'toi Monsanto Company, St, Louis, Missouri lounger I*beratorlea Certificate of Analysis - Page 6 (2/26/57) tlBLE T SKIS IHBITaTIOH IS H1B3IT3 APTEB 1PPLIC1TI03 OS 'HTDHAULIC FLUID OS-81' Animal So. numerical Evaluation At The End Of 2 Hours 24 Hours 48 Hours 72 Hours 1 1110 2 0 100 '3 1 1 0 0 Avarags 0.6 1.0 0.3 0.0 Discussion - Aftar too hours, two rabbits ahowsd barely perceptible redness for an average seort of 0.6 ont of s poaslblo 8.0. Ho odsos developed. Orsrnits very slight erythema was obssrrsd on all animals. The rsaldna was removed from tha skin aftsr twenty-four hours, two of tha animals wars given a zaro scora on tha saoond day. Hydrsulio fluid OS-81 was found to ba a rathar mild skin Irritant. TABLE TI SEES IRBITATIQ3 IS BABBITS APTEH APPLICATIOB OP 'HXDHAULIC FLUID OS-83' Anlnal Bn. Buaarical Evaluation At Ths Ibid Of 2 Hours 24 Hours 48 Hours 72 Hours 1 0100 2 1110 3 0100 Averag* 0.3 1.0 0.3 0.0 DISCUS3I0S - Tha avsrag* soora after two hours was 0.3, consisting of very alight erythema on ona animal. All rabbita showed barely perceptible redness in twenty-four hours at which time ths remaining compound was wiped off the skin. Two rabbits wars found to bs free of irritation within forty-sight hours. Hydranllc Fluid 03-83 was classed aa a rather mild skin irritant. HONS 0363**! HoiMonmapto Clwlnil cV-pany, l St. Louie, Missouri lounger Laboratories Certificate of Analysis - Fags 7 (2/26/57) Awi<w1 1 2 3 Average TABLE YU E IE IHHITAIIQB Of BABBITS AFTER AFFLICATIOI OF HTDHADLIC FLUID OS-81* Bumarical Evaluation At Zha End Of 1 Hour 24 Hours 48 Hours 72 Hours 120 Hours 86 2 2 10 6 4 2 64 2 0 0 0 0 8.0 5-3 2.6 1.3 0.0 DISCUS3101 - There was alight dlaooafort shown Immediately upon application. Tha average soar* after ana boor aaa 8.0 oat of a poaaibla 110.0. Moderate erythaaa and laoriaatian with alight adaaa waa obaerred. Tha iria waa praetleally unaffected. Ovsmite lacriaation returned to normal and tha average acore reduced to 5.}. Too of the anlnala had a alight degree of erythaaa renalnlng after seventy-two hoars Hydraulio Fluid 03-81 waa cLeased aa a mild eye irritant. TABLE YIH K IE IHBISAIIQB IB BABBITS AFTEB AFFLICATIOI OF 'EZDHADLIC FLUID 08-85* Animal Bo. numerical Evaluation At The End Of 1 Hour 24 Hours 48 Hours 72 Hours 120 Hours 1 2 5 Average 86 4 2 12 8 4 2 10 6 4 2 10.0 6.6 4.0 2.0 0 0 0 0.0 DISCUSSIOB - Zha degree of irritation waa quite similar for both Hydraulio Fluid OS-81 and Hydraulio Flold OS-83. Mild discomfort developed immediately upon application of Hydrantio Fluid 08-83. After one hour the average score waa 10.0 out of a possible 110.0. Moderate erythema of the palpebral congunotivae, considerable lacriaation, and mild edema developed. The iris remained clear and tha cornea showed little change. All anlnala still showed slight redness after seventy-two hours bat all ware free of inflaaaation by tha fifth day. Hydraulic Fluid OS-83 was classed as a mild eye irritant. HONS 036344 `las Monsanto Chasdcal Cbapany, 1 St. Louis, Missouri lounger Lsborstorlss Csrtiflosts of Analysis - Psge 8 (2/26/37) TABLE IX XHHALATIQH 07 'EIBBAULIC 7L01B OS-81' ViFOfiS BT HITS Average Temperature Inside Chamber ............................... 75*^ 7. Average Relative Humidity Insids Chamber ................... 60.0 5S Animal Ho, 1 2 3 4 Puts Survived SurriTsd Survived Surrired Observations IXirlng Exposure Animals contlmia to dots about-- Bo paving at noss or eyes-- Breathing steady. disccssioi - lo deaths oocurred during the six hours exposure nor during the subsequent two weeks observation period. Breathing and activity in general did not change naterially leading to the belief that the vapors did not cause serious discomfort. Mucous oeabransa of the nose and throat shooed only slight lnflasmatlon after exposure. Salivation was not excessive. The fluid was agitated quite briskly at ten pounds pressure per square Inch. However, little or no hase developed in the chamber atmosphere. It was possible that saturation was reached although it was apparent that the ooapound does not readily vaporise. MONS 036345 ' tot Monsanto Owlnol Voapacy, St. Louis, Missouri lounger Laborstorlss Certificate of Analysis - Pag* 9 (2/26/37) TABLE X IMH.mnit OF 'HYDRAULIC FLO IB CS-8J' TAPOBS sr BATS Average Tanpsraturo InsIds Chaaber.......... Average Relative Hualdlty lasIds Chaaber 73 .f F. 57.8 i. Fats Observations During Exposure 1 SurrlTsd Aclasis show only slight dlscaofort 2 Surrlrsd Coatinus to szplars csgs. 3 Survived 4 Survived DISCUSS101 - Tht Missis survived ths exposure olthoat loeldant. The behavior pattorn saa rery alallar to Hydraulic Fluid OS-81. lo azcaaslTa lacrimatloa or sallTatioa was noted. Activity was not neterially reduced. Inflaaaatlon of the nose and throat was vary alld to mild. Air pressure of ten to twelve pounds per square inch agitated the fluid vigorously but apparently droplets ware not carried over into the chaaber. The fur of the animals remained dry. As with Hydranlio Fluid CS-81 very little vapor hast accumulated in the chaaber. The vapors of both Hydraulic Fluids were considered to be only aildly Irritating to rats. -si . MQNS 036346 fos Monsanto Chanioal^ jpany St. Louis, Missouri ( lounger Laboratories Cartlficata of Analysis - Fag* 10 (2/26/57) SCMMAHT Toiicologioal Investigation Of two nev Hydraulic Fluids produced the following resultst hipbabuc runs oa-ai Orel LDjq (Hats) -- 3.60 Grams per Kilogram (Fiducial Limits 8.12 to 5.0} Cm./Kg.) Minimum Lethal Oral Loss (Babbits) -- 0.35 to 0.50 Gram per Kilogram. Skin Irritation (Babbits) -- Bather Mild Skin Irritant: Average Maxi mum Score - 1.0 out of possible 8.0. Ore Irritation (Babbits) -- Mild Eye Irritant: Average Marlmum Score - 8.0 out of possible 110.0. Vapor Inhalation (Bats) -- Bo Deaths, Mild Effect. HTD8ADLIC FLUID 03-83 Oral LD^q (Bats) -- 34*3 Crams Per Kilogram (Fiducial Limits }2.6 to 36.5 Ga./Kg.) Minimum Lethal Oral Loss (Babbits) -- 4.25 to 5.00 Crams Per Kilogram. Skin Irritation (Babbits) -- Bather Mild Skin Irritant: ivaraga Mat!cuts Score - 1.0 out of possible 8.0. Eye Irritation (Babbits) -- Mild Eye Irritants Average Mvrlmia Score - 10.0 out of possible 110.0. Vapor Inhalation (Bats) -- Bo Deaths, Mild Effect. YODBOEB LAB0HAT0RIE3 . . nv.y hr >,' .* *:. ' T .:* ts ..a \y i". c ' .'.MirT::;.1, . - r\ \ v ' *) b' 1; a " ; c;.. - t > tn-' Ii ,-i L0-I3 f'.' .V -- MOil. L 3p7t* HONS 0363**7