Document q1G3EkYpExGYVGk0NwDmJwXq
Younger Laboratories
UfockemUid.. . . PkabmcuxUoqidij.. . . Aaalytt\t
Route 9 -- Box 281
ST. LOUIS 23. MISSOURI Phone TIloen 6-2540
Certificate of AmtifUd.
February 26th, 1957
SUBJECT -
Toxicological Investigation Of: Hydraulic Flnid OS-61 - Monsanto Sanple Bo. 1 Hydraulic Fluid OS-65 " Monsanto Sample Bo. 2
Monsanto Project Vo. T-57-1
l.-;
TESTS COlfXJUCTED FOR Monsanto Cheaical Company, St. Louis, Missouri
EXFBRIMHffAI PBQC2DURE -
A) Oral LD-. In Bata
-
Each undiluted compound was introduce
strain albino rats by means
Minimum Lethal Bose was
blanket the toxicity r;
This was done aCo*ding faf a modifici
Observations wpf><nffae f<
selected
>oachs of Sprague-Lawley
After the approximate a were fed at levels designed to
data for calculation of the LDC~ the method of Bliss. f toxicity and the viscera of examined macroscopic-ally.
The data are
le II.
B) The Mini ana L^^al Oralise For Babbits Hew Zealand whrjje'-sabfe^s were fed orally varying amounts of te3t compound. The viscera of anX&add'xhat succumbed was examined microscopically.
The data are found in Table III and Table 17.
C) Skin Irritation In Babbits Undiluted sample was applied to the closely clipped, intact 3kin of albino rabbits and observations made over a period of several days for irritation.
The results, based on the scoring technique of Braize, Woodard and Calvary (J. of Phans, and Exp. Therapeutics, Tol. 82, Vo. 4, Dec. 1944), are shown in Table 7 and Table 71.
D) Eye Irritation In Babbits
0.1 Ml. of undiluted sample was placed in the conjunctival sac of the right eye
of each of three albino rabbits and the degree of irritation scored according
to the method of Braize, Woodard and Calvery (J. of pharm. and ihcp. Therapeutics,
Tol. 82, Vo. 4, Deo. 1944).
*
The data are found in Table 7U and Table Till.
Thia ronfahiiHd wpwt is doc to bs uaod is 4By form of advartuotf witboat writtsw p
0363928
TOXSTUDIES0420
To: Mon--nto Chemical tompasy, St Louis, Missouri
Younger Laboratories Certificate of Analysis - Page 2 (2/26/57)
EXP&HDCESTAL PflDCKDOBE - (Continued)
E) Vapor Inhalation In Eats Pour mature male rats were placed in a metal chamber of approximately 50 liters capacity and exposed for six hours to an atmosphere of hydraulic fluid rapore produced by aspirating the compound at room temperature. The liquid was poured into a three hole, round bottom flask and compressed air passed over an orifice, the lover end of which was immersed in the liquid. A glaas tube led from the flask into the chamber. A glass impinger was placed in the line to break up droplets and allow, as nearly as practicable, only vapors to pass. The animals were observed for behavior and, since there were no deaths, all rats were held for tvo weeks additional observation.
.
+$ \-'*y' ';-y.
The data are shown in Table IX and Table
0363929
TOXSTUDIES0421
, to* momam uaeaicaj. ^.^pany,
%
St, Louie, Missouri
lounger Laboratories Certificate of Analysis - Page 3 (2/26/57)
TABLE I
THE ORAL LB OP 'HYDRAULIC FLUID 0S-Q1' 3 FOR BATS
Animal Bo. - Sex
1- Female 2- Female 3- Kale 4- Female 5- Male
6- Hal. 7- Female 8- Female 9- 7aula 10- Male 11- Male
12- Female 13- Female 14- Female 13- Male 16- Hal. 17- Female
13- Male 19- Female 20- Famala 21- Male 22- Female
Weight Go,
24C 210 255 210 225
245 215 200 220 250 210
190 195 215 230 255 200
240 195 205
235 215
Lose Ge. / Kk.
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 0.25 3.25 8.25 8.25
9.00 9.00 9.00 9.00 9.00
Fate
Survived Died
Survived Survived Survived
Died Survived Survived Survived
Died Survived
Died Survived Survived Survived
Died Survived
Died Died Survived Survived Died
DISCUSSIOH -
The Oral LD5_ was found to be 8,60 grans per kilogram with fiducial limits of 8.12 to 9o3 grama per kilogram. Survival time was ovemite to four days. There wao diarrhea, irritability, and nervousness observed. Some survivors lost as ouch as 5C$ of their starting weight before regaining normal appetite.
At autopsy there was liver damage, moderate kidney congestion, and gastrointestinal inflammation.
1
OJbV^0
TOXSTUDIES0422
To: Monsanto Chemical Company,
*
St* Lou3t Missouri
Tourer Laboratories Certificate of Analysis - Page 4 (2/26/57)
T A B L II
THE OdAL LD-- OF 'EYDdAULIC FLUID CS-63* ? FOH HATS
iml No. - 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- Hale 14- Female 15- Female 16- Female
17- Hale 18- Hale 19- Female 20- Female 21- Female
Weight Ca,
210 220 205 240 210
195 205 215 230 250
190 200 225 135 195 215
240 255 230 210 205
Bose Ga. /Kg.
27.5 27.5 27.5 27.5 27.5
30,0 30.0 50 J) 30.0 30.0
35.0 35.0 35-0 35.0 35.0 35.0
40.0 40.0
40,0 40.0 40.0
Fate
Survived Survived
Died Survived Survived
Died Survived Survived
Bled Survived
Survived Bied Bied
Survived Bied
Survived
Bied Survived
Died Bied Bied
%
>
BISCCSSIOI -
Tha Oral LD^g was placed at 34*3 grans per kilogram with lower and upper limits of 32.6 to 30.5 grams per kilogram. Survival time was two to seven dayo. Severe diarrhea, trembling, irritability, and lethargy developed, Weight losses ran to 2yp of starting weight.
At autopsy the atonauh was gaseous end irritated. The liver was discolored sr.d hypereoic. There was also pulmonary congestion.
\ fi/.&S-
0363^31
TOXSTUDIES0423
'Toi Monsanto Chemical Company,
'
St. Louis, Missouri
lounger Laboratories Certificate of Analysis - Page 5 (2/26/57)
TABLE HI
THE MTHTMHM T.CTHAT. ORAL BOSE 0? 'HYDrtAULIC FLUID OS-61 ' FOR RABBITS
AtHitiHo. - Sex
1 - Hale 2 - Female 3 - Male 4 - Male 5 - Male 6 - Female 7 - Female 8 - Hale 3 - Male
Weight Kg.
2.0
1.9 1.9 2.3 2.1 1.8 1.8 2.3 2.3
Dose
0.25 0.35 0.50 0.75 1.00 1.50 2.00 3.00 5-00
Weight Change 4 Days After
Dosing
0.0 55 0.0 ?s -15.0 p -10.0 % -15.0 f. -12.0 $ -20.0 $ -18.0 ^ -15.0
Fate
Survived Survived Died--4 Days Died--4 Days . ' Died--7 Days Died--4 Days
Died--5 Days Died--5 Days Died--5 Days
. . C'
EISCUSSIOS -
The >^ww Lethal Dose was in the range of 0.35 to 0.50 gran per kilogram. Survival time was four to seven days. The animals gradually became Teak from Iobs of appetite. There appeared to be partial paralysis after two to three days.
At autopsy liver and spleen were congested. There appeared to be blood changes.
TABLE IV
THE MDfUfUM LETHAL ORAL DOSS OF 'HYDRAULIC FLUID OS-63' FOR RABBITS
AnInal Ho. - Sex
1 - Male 2 - Female 3 - Male 4 - Female 5 - Male 6 - Ifela
Weight
Kg-
2.6 2.1
2.4 1.9 2.4 2.2
Dose Gm. / Kg.
2.25 3.00 3.50 4.25 5.00 6.50
Weight Change 4 Days After
D osing
0.0 51 + 4.0 f.
0.0 5; - 8.0 Ja -13.0 $ -10.0 f'
Fate
Survived Survived Survived Survived Died--5 Days Died--6 Days
Discussion -
The Minimim Lethal Dose was 4.25 to 5.00 grams per kilogram. Survival tine was five to six days. Weight losses resulted from poor appetite. Animals Ho. 5 fmrf Ho. 6 gradually became lethargic but did not appear to develop paralysis.
At autopsy kidneys, liver, and lungs were all hyperemic.
0303932
TOXSTUDIES0424
f Tot
Monsanto
Chantcal
CVompany,
t
St. Louis, Missouri
Tcmngsr Laboratories Certificate of Analysis - Page 6 (2/26/37)
TABLE 7
SEES IRRITATION HI BABBITS AFTER APPLICATION OP 'HYDRAULIC FLUID OS-81*
Animal No.
Numerical Evaluation At The End Of 2 Hours 24 Hours 48 Hours 72 Hours
1 1 110
2
0
10
0
3
1
10
0
Average
0.6 1.0 0.3 0.0
DISCUSSION -
After two hours, tvo rabbits shoved barely perceptible redness for an average score
of 0.6 out of a possible 8.0. No edema developed. Ovemite very slight erythema
vaa observed on all animals. The residue vae removed from the
after
twenty-four hours* Tvo of the animals were given a zero score on the second day.
Hydraulic Fluid OS-81 vaa found to be a rather mild shin irritant.
TABLE VI
SECT IRRITATION Iff RABBITS AFTER APPLICATION OP 'HYDRAULIC FLUID OS-83*
Animal No.
Numerical Evaluation At The Bid Of 2 Hours 24 Hours 48 Hours 72 Hours
1 2 3
Average
0 100 1 110 0 100
0.3 1.0 0.3 0.0
DISCUSSION -
The average 3core after two hours was 0.3> consisting of very slight erythema on one animal. All rabbits shoved barely perceptible redness in twenty-four hours at which tine the remaining compound was wiped off the skin. Two rabbits were found to be free of irritation within forty-eight hours.
Hydraulic Fluid OS-83 was classed as a rather mild skin irritant.
'*v^
TOXSTUDIES0425
Hot Hoaaaato Cbanieal cV-pacy,
V
St. Louis, Missouri Tousgtr Laboratories Cartifleata of Analysis - Fags 7 (2/26/57)
Apilmal JfO.
1 2 3 Average
TABLE 711
E IE IBHITAIIOH IB BABBITS AETEH APFLICATIOH OP `HTDflADLIC PUTED OS-81'
numerical Evaluation At Tie End Of 1 Hour 24 Hours 48 Hours 72 Hours
86
10 6 64
2
4 2
22 0
12Q Hours
000
8.0 5.3 2.6 1.3
0.0
i-i; ' r.'/\
DISCUS3I0H -
There was slight disoomfort shown immediately upon application. The average
score after one hour was 8.0 out of a possible 110.0. Moderate erythema end
l&orimation with slight edema was observed. The iris was practically unaffected.
Ovemit# lacrim&tion returned to normal and the average score reduced to 5*5.
Two of the
had a slight degree of erythema remaining after seventy-two hours.
Hydraulic Plaid OS-81 was classed as a mild eye irritant.
Jn-imVl ffp,
1
2 3
Average
TABLE VIII
ETE iaaiTATIQH IB BABBITS after application op 'HIDBAULIC FLUID OS-831
Numerical Evaluation At The End Of 1 Hour 24 Hours 48 Hours J2 Hours
86 4 2 12 8 4 2 10 6 4 2
10.0
6.6
4.0
2.0
120 Hours
00
0
0.0
DISCUSSION -
The degree of irritation was quite similar for both Hydraulic Fluid CS-61 and
Hydraulic Fluid OS-83. Mild discomfort developed immediately upon application
of Hydraulic Fluid OS-83. After one hour the average score was 10.0 out of a
possible 110.0. Moderate erythema of the palpebral congunctivae, considerable
lacrination, and mild edema developed. The iris remained clear end the cornea
showed little change* All animals still showed slight redness after Beventy-two
hours bat
were free of inflammation by the fifth day.
Hydraulic Fluid 03-83 *as classed as a mild eye irritant.
m
036393*
TOXSTUDIES0426
'To: Monsanto Chemical Annpany,
^
St. Louis, Missouri Younger Laboratoriss Certificate of Analysis - Page Q (2/26/57)
TABLE IX
IHHAIATIQB 07 ' ETxfiAULIC JLUXD CS-Sl* 7APCBS BY EATS
Average Temperature Inside Chamber ........... .................... 75.? Average fielative Humidity Inside Chamber.................... 60.0 fo
Animal Ho.
1
2
3 4
Tate
Survived Survived Survived Survived
Observations During Erposure
Animals continue to move about-- Ho paving at no9e or eyes-- Breathing steady.
Discussion -
Ho deaths occurred during the six hours exposure nor during the subsequent tvo weeks observation, period. Breathing and activity in general did not change materially leading to the belief that the vapors did not cause serious discomfort. Mucous membranes of the nose and throat shoved only slight inflammation after exposure. Salivation vas not excessive.
The fluid v&s agitated quite briskly at ten pounds pressure per square inch. However, little or no haze developed in the chamber atmosphere. It was possible that saturation was reached although it was apparent that the compound does net readily vaporize.
-M*k; 03631*Vi
TOXSTUDIES0427
' To: Monsanto oh****^ coapacy,
'
St. Louis, Mlaaoori
Younger Laboratories Certificate of Analysis - Page 9 (2/26/57)
. TABLE X
IBHALATXOH OP 'HYDRAULIC FLOIB CS-65' VAPORS BY RATS
Average Temperature Inside Chamber ..... Average Relative Humidity Inside Chamber
73.S" ?. 57.8 Ji
>nima.l ]fo#
1 2 3 4
Fate
Survived Survived Survived Survived
Observations During Exposure
Animals show only slight discomfort. Continue to explore cage.
BlSCOSSIOf -
The animals survived the exposure without incident. The behavior pattern was very similar to Hydraulic Fluid OB-81. 5o excessive lacrimation or salivation was noted. Activity was not materially reduced. Inflammation of the noae and throat was vary mild to mild.
Air pressure of ten to twelve pounds per square inch agitated the fluid vigorously hut apparently droplets were not carried over into the chamber. The fur of the animals remained dry. As with Hydraulic Fluid CS-81 very little vapor haze accumulated in the chamber.
The vapors of both Hydraulic Fluids were considered to be only mildly irritating to rats.
0383*' 30
TOXSTUDIES0428
To: Monsanto Chemical^ apany,
(
St. Louis, Missouri
'
Younger Laboratories Certificate of Analysis - Page 10 (2/26/57)
..
SUMMARY -
Toxicological Investigation. Of two new Hydraulic Fluids produced the following results*
HYDRAULIC FLUID 03-61
Oral LU^q (fiats) -- 8.60 Crams per Kilogram (Fiducial Limits 8.12 to 5*0? Gn./Kg*).
Minimum Lethal Oral Lose (Babbits) -- 0,35 to 0.50 Gram per Kilogram,
,.^4V-
Skin Irritation (Babbits) -- Hatier Mild Skin Irritant: Average Mariimim Score - 1.0 out of possible 3.0.
Eye Irritation (Babbits) -- Mild Eye Irritant: Average Maximum Score - 8.0 out of possible 110.0.
Vapor Inhalation (fiats) -- Mo Deaths, Mild Effect.
. . .vV. i*-
."i;
HXDBAPLIC FLUID OS-8?
Oral LD^q (Bats) -- 34.3 Grams Per Kilogram (Fiducial Limits 32.6 to 36.5 Cn./Kg.).
Minimum Lethal Oral Dose (Babbits) -- 4*25 to 5*00 Grama Per Kilogram. Skin Irritation (Babbits) -- Bather Mild Skin Irritant:
Average touicmm Score - 1.0 out of possible 6.Q.
Eye Irritation (Babbits) -- Mild Eye Irritant* Average Maximum Score - 10.0 out of possible 110.0.
Vapor Inhalation (Bats) -- Do Deaths, Mild Effect.
YOUNGER LABORATORIES
-- Mo::..-: L ..U-V-p-n;' 0363937
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