Document EvqKN7Lg2ygagkYGk4D5o8e3j
r.
Younger Laboratories
BiocktmUU... PhatmacdaqUii ... Analfiti
isa cLirr cvi road
Saint Louis, Mo, mim
PHONIl TILOIN 6*9 840
Geniijfiocde AnaLfAM,
SUBJECT -
Toxicological Invaatlgatlon Ofi MCS 39 9 Monsanto Sample Number 244 Moaaanto Project Number Y-65-213
January 10th, 1966
I`%>
STUDY CONDUCTED rOA Monaanto company, St. Louis, Mlaaourl
EXPERIMENTAL PHOCEDUHE -
A) Oral LDS0 (Hats, Mixed Se:
The undiluted compound male and Yenale rata*
ibe to Sprague-Dawley strain albino
After tha appri
female rats we; Intervals at supplying da' modification o'
lose was determined, groups of male and 6see at increments of 0*1 fractional log to blanket the toxicity range thereby ion of the LD50 which was done according to a If J. do Beer*
Observations succumbed sere exam!
__ toxic symptoms and the viscera of the animate that 'macroscopleally.
The data ara shown in Table I*
B) Oral KLD (Rabbits, Mixed Sex)
-
The undiluted compound was fed la increasing doses at increments of 0*2 fractional log intervals by stomach tube to New Eealand white male and female rabbits*
Observations sere made for toxic symptoms and the viscera of the animals that suoouabed sere examined nacrosoopieally*
The data are shown la Table II*
Tbit ooafidantial rapon knotto b* ond ia *iT font of dvattbiae wUkool writuo immiluly HONS 036445
twi Monsanto Compmny
;" : AH' . , . 1
tt Louis, Missouri
:-..-v:4..
Touagsr Inborntoriea Certificate of Analysis - Pago 2 (1/11/66) . T-6V21)
EXPERIMENTAL PROCEDURE - (Continued)
C) Skin Absorption KLD (Babbits, Mixed box)
The uadlluted eoapound ooo appllad la lncreaainj doses at incrsaeata of 0.2 fractional log intervals to tbe closely clipped, intact skin of Nee Zealand white Bale and female rabbits.
The treated areas were covered with plastlo strips and the animals placed in wooden stooka for pariods up to twenty-four hours, after which tine they were assigned to Individual cages.
Observations were node for toxic symptoms and the viscera of the animals that succumbed were examined nacroacopically.
The deta are shown in Table III.
::) Skin Irritation (uabblts. Mixed sex)
The undiluted oompound was applied to the clipped, intaot skin of male and female albino rabbits and removed after twenty-four hours. The applicatior was covered with plastic strips to retard evaporation and avoid contsninatior..
Observations wart made over a period of several days for irritation.
The dfta, scored according to the mot! oil of jraize, 'codard end falt er;
(Journal of fharv. and Exp. Therapeutic:., Volume bi, ferer.ter, 1944) are sheer.
In Table IV.
-
E) Eye Irritation (Rabbits, Mixed Sax)
C.l Milliliter cf undiluted cie,lr trr place: in to cr.-.juhotival sac. oi the right ays of thras albino rabbits and observations mode over w period of several days for inflammation.
The oyec ware rinsed with warm isotonic suliui solution after tr.t,-fo'.r dcjrc.
The data, scored according to the method of Oraize, et al, are shewn In Table V.
F) Vapor Inhalation (Mnls Rats)
Four nature mala rata ware placed in e metal chamber of 3) liters cc.'olt'1 and axpoaad for six houra to a concentrated atmosphere of vapors produced by passing a stream of air through lb*, milliliters cf the compound contained In a Joo milliliter zxlenmeyer flask. Viporr fret the flask passed into a one liter bottle to ronovo droplets and than into the chamber.
Air flow through tho saaplo was flvw liters per ainute an neaoured by a cali brated rotameter. This was sufficient to violently agitate the liquid. No supplementary air was introduced inasmuch as tne aeove supply was am;lw for the animals oxygen requirements.
The animals sera observed for behavior and, alnco there war# no deaths, all wars held for tan days observation.
The data are shorn in Tabls VI.
MONS 036446
Toi Monsanto Compmny St. Louis, Missouri
Younger Laboratories Certificate of Analysis - Page 3 (l/U/6h) - T-65-21S
SOMHART HCS__3 9 5
A) Oral U>,0 (lists. Mixad Sox) Ths Oral Luj0 *or *a3e and female rata aas placed at 4ol5 ailiigrams par kilogram with losar and upper Halts of 4060 to 526o allllgrana par kllogre.r. The compound aas olaasad as slightly toxic by oral Ingestion la sale and faaala rats.
B) Oral Mill (Rabbits, Mixed Sex, The Klnlsus Lethal oral l)eoe for sale and female rabbits was found to be greater than 1500 allligrams per kilogram and less than 2510 nllllgraas per kilogram. The cospound aas elassed as slightly toxic by oral Ingestion In male and female rabblta.
C) 3kln Absorption MLD (Rabbits, Mixed Sex) The Minimum Lethal Dose by skin absorption In male and female rabbits aas found to be greater than 2510 milligrams per kilogran and less than JdBe mllllgramr per kilogram. The compound aas classed as slightly toxic by akin absorption In male and finals rabbits.
D) Skin Irritation (Rabbit.,, Mixeu sex; The oompound saa classed ae non-irritating enen applied undiluted to the intact skin of male end female rabbits.
i) -ye Irritation (Rabbits, Mlxeo hex; The compound aas classed ss a slight eye irritant In male and female rabbit.-., Tha average maximum score aas 6.3 out of a possibla 110 in ona hour.
T) Vapor Inhalation (Male Aats> All animals survived the six hour exposure as aall ss the following ten day bearvatlon period. It aas ooneluded that tha vapora were practically non-toxic under conditions of tha test.
YOUIvj -h LABOKAIVSI-o
BYl FK10 K. fOOKSSR
MONS 0364*7
ToI Monsanto Company St. Louis, Missouri
lounger Lbor*torio Certificate of Analysis - page 4 <1/10/66) - y-65-21}
T A t 1 i, I
THL ORAL L D 50 OP 'M C S 395' POH RATS
Semple Fad undilutad
Animal No. - Sex
1- Tamale 2- Male 5- Female 4- Male 5- Fannie
6- Kale 7- Female 8- Male 9- Female 10- Male
11- Female 12- Male 1>- Female 14- Male
l6- Male 17- Female 18- Male 12- Fea*lc 20- Male
Weight QB 0
225 240 220 255 255
260 230 27c 2 35 255
23C 2i5 225 265 235
26c 225 245 24C 26d
Dose
3160 3l6o 316c 3l6c 316u
3980 3980 3980 398c 396c
901c 5oio 5oio 5oio 5oio
6310 631c 6310 6310 631C
Fate
Survived Survived Survived Survived Survived
Survived Died
Survived Survived Survived
. Died Survived Died Survived Died
died Died Died Died Died
DISCUSSION -
Tbs oral LDj0 for male and fanale rats ms plaead at 4615 milligmma par kilogram with lower and upper Halts of 4c6o to 526c milligrams par kilogr-j-.. The compound oas classod as slightly toxic by oral ingsation in aala and feaala rats.
Survival tins ms savaral hours to three days with most deaths occurring overnight* Toxic symptoms includad severe diarrhea, increasing weakness, treaors, and collapse* At autopsy there was lnflaaaatlon of the gaatrlo aucosa and renal hypereaia macroaoopioally.
MOMS 0366*8
To: MonMato Company St. Louis, Missouri
Touagsr Laboratories certificate of Analysis - Fags 5 (1/10/66) - Y-65-21J
TABLE II
THE MINIMUM LETHAL OPAL DOSE OF 'MCS 395' FOP RABBITS
Sample Fed Undiluted
Animal No. - Sex
1 Female 2 - Male 5 - Female 4 * Male 5 - Female 6 - Hale
Weight .5X1.
2.6 J.o 2.7 3-1 2.7 2.9
Dose SBl/.iBi
631 1000 1580 2510 3980 6310
1
0
H*
".'eight Change 5 Days Later
K0.0 + 0.1
- 0-4 - 0.3
Fate
Survived Survived Survived Died -- 6 Days Died -- 5 Days Died 2 Days
DISCUSSION The Minimum Lethal Oral Dose for male and female rabbits was found to be greater than I960 milligrams per kilogram and less than 2510 milligrams per kilogram. The compound was classed as slightly toxic by oral ingestion in male and female rabbits.
Survival time sas tvo to eight days. Toxic symptoms in animals #4 and P5 included poor appetite in tso to three days, weight loss, increasing weakness, tremors, and collapse. At autopsy there was evidence of liver dysfunction and renal hyperemia.
The wetsrSn! i;-. '.'-b IV.-; vo-;-..- : r. K
] .
mc.:t in L;. Louii jo;
- - , v- : : ' VT
Monsanto
Ccripcr.* HUNS 036449
TO! Monsanto Company
St.Louis, Kiasourl
_
Younger Laboratories Certificate of Analysis - Pago 6 (1/10/66) - y>6J-21)
tabu; hi
THE MINIMUM LETHAL DOSE OF 'MC S 595' BY SKIN ABSORPTION IN RABBITS
Baapi* Applied Undiluted
Animal No. - Sex
Weight
.SAz.
Dose
t'Bz/.SBz
.Veight Change 5 Days Later _____ Kg,.
1 - Male
3.0 631
2 - Female 2*5 1000
J - Male
2.8 1560
4 " Female 2.4 2510
5 - Male
2.5 3960
6 Female 3.1 6310
0.2 + 0.1 + 0.1 - o.l - 0.3 - 0.2
Fate
Survived Survived Survived Survived Died - 7 Days Died - 9 Days
DISCUSSION Th* Miniauo Lethal Dos* by Skin Absorption In male and f*aal* rabbits was found to ba grsatsr than 2510 mllllirrams per kilogram and l*sa than 3980 milligrams per kilogram.
The compound was classed as slightly toxic by skin absorption In male and fsmale rabbits.
Survival tin* was ssvan to nine days. Toxic symptoas In anlaals jV5 and #6 included raduoad appetite and activity in thra* to four days with increasing weakness, dyspnea, and paralysis. At autopsy the lungs were hemorrhagic and there was liver discoloration naoroseopleally.
HONS 036430
Toi Monsanto Company St* Louis, Missouri
Younger laborstoriss Csrtlfloats of Analysis - Pago 7 (1/10/66) - 1-65*213
TABLE IV SKIN IRRITATION IN RABBITS AFTER APPLICATION OF 'MCS 395'
Ssapls Applisd Undiluted
i5iS!l.SSi.:.!5
Nuaerioal Evaluation At Tbs End Of l.gour 24_Hour jfl_Hours J2_Houro 129_Hours
1 - Fsnale
0
0
0
0
2 - Msls 0 0 0 0
3 - Fsaals
0
0
0
0
0 0 0
DISCUSSION Ths eonpound ms elssssd as non-irritating to intsot rabbit skin when applisd undiluted.
No sdaaa or erythema dsvslopsd on any of ths animals as a result of a tssnty-four hour exposure to the undiluted compound. All aniaals received a score of sera throughout the observation period*
MONS 030451
Tot Mouuto CMPU7 8t. Louis, Missouri
Imaser Laboratories Certificate of Analysis - page 8 (1/1Q/66) y-65-213
TABLE V EYE IMITATION IN BABBITS AFTER APPLICATION OF 'MCS 395'
Saaplt (0.1 Millilitsr) Applisd Undiluted
Animal No* Sex
Nuaerloal Evaluation At The End Of l_Bour 24_{jours 46 Hours 72 Hours 120_Jours
1 - Female 7 4 2 C
2 - Hale
74 4 0
3 - Female 11 6 4 2
0 0 0
Average
8.3 4*6 3.3 0.6
0.0
DISCUSSION Tbs compound was classed as a sligilt eye irritant in aale and female rabbits. The average aaxiaua soore eas 8.3 out of possible 110 in one hour.
Little discomfort aaa shown iamediately following application.
After one hour there was slight discharge and redness, practically no edema, and very slight corneal dullness. Iris and cornea were clear in twenty-four hours and within three days only a trees of redness of the palpebral conjunotivae remained on one animal.
HONS 036452
To i MonMnto Capoy
3t. Louis, Missouri Younger Lsborstorlss Csrtifioste of Analysis - page 9 (1/1C/66) - y-6j-2lj
table; vi INHALATION Of 'MCS 595' VAPORS BY RATS
Average Temperature Inside Chamber ..................................................... Average Relative Humidity Inside Chamber ........................................
Amount of Sample -- To Start ................................. Recovered ............................... Vaporised or left in equipment ....................
1C0-0 cc 99*7 eo
0.3 cc (G.Jfc)
^6 F. 43 %
45iKi.!!2i ~_ex
1 - Male 2 - Male } - Male 4 - Kale
____ Fte______
Survived Survived Survived Survived
____ 2^5!n?iiS55-9SriS6.55iSS!fS___ __
No immediate reaction
Normal breathing rate ...
No discomfort or nasal discharge ...
No weakness ...
.
Moderate lethargy after two hours.
DISCUS..ION All animals survived the cix hcur exposure a.' "ill as the following ten day observation period.
It was concluded that the vapors were practically non-toxic under conditions of the test.
The animals appeared to be unaffected by the exposure. Nasal and ocular mucosae were normal when the animals were removed tror the chamber. The ten day observation period was uneventful.
MONS 036453