Document BxNwnnk5vyK0L1Xg5xznEbk4
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'
Younger Laboratories
3i<tt*Ut4 ... Piuumamltfiitt... <QualfdU
rl a* CUFF CAM ROAD
AINT LoliU. Mu, Mtisv
Ge/Uifccate
AaaLfdHPlONIi TILDBN 6-II4B
February 15 th, 1964
SVBJBCT -
TWliellfiMl Iav--Ugatloa Of: FH - 14} Iwaute S--ple ba--vr 7 IIORB--to Preject b--bar Y-64-7
STCDY COVDVCriZ) FOR NoMMto Cbeoiool Coapaay, St* Loula, Hlaaouri
mDWfll FdOCBMIBK -
S) Oral UM (Bata, Mlxad S--}
Tho --dilated i--poe-- rrr fad bp ato--eh tuba to Sprafue-Daaley atrmln alM-- --la ud fa--1* rat*.
After tba approxi--te dial-- botbal liMa aaa dateralaad, groupa of --la and fa--la raw vara fad la laereodlag do--a at iaereaeata of 0-1 fractlo--i log Utarvala at f--r lavala darig--* to bUakat tba toxicity raaga thereby --pplpibg data for aalovlati-- of tba li>9 which a-- doaa aeeordiag to a Bodlfloatloa of tba --thod of X- J. da Baer.
Obaarvatlo-- re --da far toxic ayapto-- and tba alacara of tba aai--la that iwmMdud vara ex--d--d --oreacopically*
tba data ara alto-- la Table I.
B) Oral KU> (Babbit*, Hlxad Sax)
Tba --dlivtad itaopa--d --a fad la Lacreaaiag doaaa at lacr--ta of 0*? fv--Uawkl lag latarvala by ato--eh tabe to Net Zealand atilta fa--la and --! rahhdha.
IBaanaU-- --ra --da for toxic a/ipt-- aad tba rlacara of the aai--la that a--a--bad aora a--tail --aro--opleaily*
Tba data ara alio-- la Ihble IX.
HbmlbMhl ---- b-- ta --db>--rb--<d'
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To; Monsanto Jheaical C^^aay
St. Louie, Missouri
Tow(*r
Certificate of
(./i '/64,
KPnDUNTAl. PKCCm - (Coatloaedj
C) Skin Absorption! HU) (Babbits, Mixed iax)
The uaAlluted coajouad ana applied in xAcreaain.- .?.* at ucrHiat* o ' .
fmetionnl lg intervals to the closely clipped, 1 .t .ct .*in of
^walsnd
itlti aale and fMl* rabbit*.
Th# tmt*4 arose vara cotarad with plastic stripe and th aniaela placed in woodam stocks for periods up to twntyfour hours, after which tia# they vara , assigned to Individual cf#a
Observation# wore aada for toxic symptoms tnd th riseera of th* am.as 1b that succumbed vara examined aacroecopicilly.
Th# data ara alioan la rbl* 111.
0) Skis Irritation (Rabbits)
Tha undiluted (loajouad aaa appliad to the clipped, inuct **in of <<lblao rabbltn and removed after tventy-four hours. Tha application ms covered with plastic trip# to retard evaporation and avoid contamination.
Obaarvatloaa vre aada over a period of several -lays fer irritation.
The data, scored according to the vetbod of oral*#, eoodard and Calvary (Journal of r'hara. and top. Therapeutics, Volume d2, Decanter, 1944/ are above la Table IV.
9 9* Irritation (Babbits)
0*1 Milliliter of undiluted sample aaa placed ia tha conjunctival sac of the right aye af each of thraa albino rabbits and observations aada over a period of aovermi days for iaflaanatloa.
Tha eyas vara rinsed aith vara isotonic aalina solution after teeotyfour hour*.
TIM data, scored according to tha aethod of Drslta, at al, are ahovn in table V.
?) Vapor Inhalation (Mala Bata)
Tour 150-gma aale rata ear* placad la & glass desiccator, % m in nv*ter,
aAd exposed for b hour# to .i coaceatrated ataoaphara of vapors produced by
panning a atraaa of air through 1^0 allliliters of tha coapound contained in a
250-nilliliter
) fora gas va&hing bottle with fritted disc. Vapors froa
the bottle passed iato a one liter oottle to react > droplets and then into tha
chamber.
Air flan through the naapla aaa 6 liters par alnute as measured by a calibrated Ntaaeter* This aan sufficient to violently agitate the liquid. Mo suppleaeattry air aa latredwted inaaauch an the above supply vaa ample for the aaiaala jxygea requirements.
9ie aniaale vai*a observed for behavior and, since there ware oo ceetrie, <11 *#rv bald for tea days obaarvatioa.
The data ara nhova in Table VIv
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fiai Moaacato Choclcal Cd^nay It* Ldtl*, MjimotI
TMk|f UkontrlH Cartlfioata of Aaalyala fraga J {2/15/64) - T-$4-7
ULuUU A) On* U>* (kto, Maad Aw)
Aa Oral U>,* for aala lal fMd nt ana plicad at 66*0 aUUgrMa par kllograa attb Low ul appa' UAta of 5575 to 2*5 niUfTMw per kilo*rma. Aa mpwul mm elMMl aa prutlitll; ao>toxia by oral iogaatioa la cala mad faaala rata.
I) Oral HU (Abblta, ttlxad Am) Tba IHaiaaa Latbal Oral ooaa for aala and ftaalt rabblta aaa faaad to ba graatar Mm 100k dUlgraaa par Xliogran and laaa than 1500 allligraaa par KIW*--* Aa caarpooad ms cluaad aa dldly toxic by oral lagaatloc ia aala and faaala rabblta.
0) Ada Abaarptloa KLD (BabbiU, Nlxad tax) Aa Hialna Latnal i>aaa by Akla Abaarptloa ia aala and faaala rabblta aaa faaai ta ba fraatar than 2510 dlllgrana par kilograa and laaa than >980 allllyraaa par klligiaai Tba coapoaad aaa olasaad aa allfbtly toxic by Mtln abaarptloa In aala aai faaala rabblta.
0) Ada IrrlUtloa (BabblU) Aka aoapaaMd aaa claaaad aa a aodarata dda irritant abac applied oadllatad ta lataat rabbit afcia. Aa atlaa aaora aaa 4.0 Mt of a paaaibla s la taocty-foor baara.
D Ifra IrrlUtloa (labblta) Aa convened aaa elaaaad aa a did to aodarato ya irritant. Aa ararnga aaxlaua acorn aaa ?>( oat of a peaalblo UO la oca beer.
f) Vapor libalatlab (Mala Ata) All --auraland tba six hour axpoaora aa aall aa tba following taa day llMmUM pariod. It ana oMtladad that tba vapora aara aUghtly toxic andar cooditiaca of tba taat.
TCVMO US0AT0HK
./
A Bit ran h. Tovna
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TOXSTUDIES0647
Hi Mwiiite OMlctl i M* r--*- Imi*
msurnu of Aaaljral# - Ptt 4 (2/13/64) - T-64-7
UILI X
m oml Ld,, or
145' wi **
4*al* fad Dadllatad Vtlh
l- rBio 2- faaalt
3- Malt 4- Mala
5- faoala
6- fatal#
7* Mai*
fmB- Halt
9- ala 10- fatal#
11- Halo 12- Hala 15- Fatal* 14- F#m1# 15- Hal*
16- Hal*
17* 18-
JFramtall#*
15- Hal* 20- Halt
215 250
245 240 225
2)0 250 260 225 235
240 260 225 2)5 240
250 220 225 240 245
Do**
>,010 5,010 .,010 >,010 5,010
6,510 6,510 6,310 6,510 6,510
7,940 7,940 7,940 7,940 7,940
10,000 10,000 10,000 10,000 10,000
___
durrtvad 21*4
Aarrivad 3mrvW4 OtfflfH
Aar!aad 31*4
aralaad Dlad
Saraiaad
Suralaad 01ad 01 ad
daralaad Auraiaad
Mad Mod Dlad Mad Mad
ouetuxoi -
Tto Oral
for aala l4 faaal# rata m plaaa4 at 6680 alllisraaa pr (tilo*ra
168 loaar aai npinr l&alto of 5575 to 8285 aiUl|rM p*r kllotiti*
1W Mapoaii toa ulaaaad aa practically aoe-toxie bj oral lafaatioa la oolo and f8l vote*
AXPlnl tAlw w m to fr toji
faada
lauludad iwHill/ laorou^M inIuih, dlarrfcaa, traaora, aai
mm of a^ to ttwtffsu1 hoan daratiaa*
At aatopay khoro aa raaal, liaar, aad pulaoaarjr byp*rari.a 67 aacroaeapic wartMtloa.
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o Chtticel <4|a*p Tot
smemei. I. iMMitirl- Certificate of laalpaia * Page 5 (2/lj/bdJ - 1-64-7
rtiu i:
HI MINIMON LtTHAi voA2. 0Co& op 'PH* 14V POt BABBITS
Seapl* Pod Undiluted
1 - Mala 2 - T*ml* 5 - Male 4 - fettle 5 - Male b - fettle
*ei(ht .li:.
J.O 2.6 M 2.6 3-2 2.7
9an Sfc/.S*
651 1000 1560 2510 ym 6jio
eight Change b Da pe Later ..........5f:..........
0.2 0.0
r*e
Ourelwed Sarrired Died -- } Dope Bled -- 2 Dap* Bled -- 2 Dope Bled -- 1 Bap
OISCOUION -
The Nlalatt Letaal Oral Doee for ttle end fettle rabbite eae found to be greater tbna 1000 nllligmne per kilngrna and lees than 1580 miligratt par kilograa. TIm conpound *. claused ae nxldlp toxic bp oral lagesti.* in a*l and fenale itbUti.
Bureieal tin# a on* to three dap*. Toxic npnptona induced treners after ev?ral hours, saliaatioo, increasing ecnkneea, and collnpee.
At antnpnp there aoe pulnonar? hpperttln* Otherwise bo visceral ehig*e of conaeqaenee vere noted nneroeeoploelly.
r..tti*i 'ii . t!w prrl. > 1>U`. it , 1
Hi -1
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Um#r lab--If1-- MttlMU of Aaalyal# - Pmgm 6 <2/1 J/64) . 1-4+.7
T A t L K HI
9X KDUNBM USUAL XAi QT *n-145* T ftKIH ABJOBPnCH XlBBIW
a#pl Applied Qadllutad
1 - rml# 2 - Hal# 3 - rml# 4 - Hal# 5 - r#ml# 6 - Halt
V#lfbt Jli.
2.8 5.1 2.6 !.0 2.6 3.1
Do## Sli/Jt
651 1000 1)80 2510 3980 6)10
>#lfAt Chaafa 5 Day# L#t#r ..........Uti..........
0.1 0.0
- 0.2 - 0.4
rat#
8ar*l<r#d Survived Survived Survived 01ad -- 2 Day# Olad -- 2 Day#
OUOOftAlOM -
ft* Ml&iau# L#tA*l Jo## by Akla Ab#orptlo# in ml# aod t#al rabbit# aa* (Mid to b# mattr Hum 2510 #imra## p#r ktlocra# and 1### thu 3990 #1111 era## p#r H1>im tW ##pmm4 # la##d a# alifhtly toxlo by akin abeorptioa la ml* tad fml# rabbit#.
hirrlnl tla# m# t# day# for nla*l< #5 aad #6. Itotic ayaptma Included triaar*, loaa of *pp#tlt*t iyapnva, and incra#iiif aaakn***.
At aatopay ta#r* aaa liver di##olor#tio# ud r*nal c#ag#stioa by meroaaopl# --alaatio*.
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IrtliBBBli-- CirllfiMti of Aaal/uA* * (*& 7 (2/IV64) - 1*64.7
TABLE IV
WIN IMITATION W BABBIT* AfTES APH.ICATU# -f 'rt - 14$'
klBli Applied Ditdllutid
4ttf9L.an*.T
i.S5K
Itanorlcol raluati.oa At IB* ited Of
2^acur*
Mourn j2.Bourj l|9_dour
l6d^Mour*
1 24 3 i 1 0 2 14 3 2 0 G 3 24 4 2 1 0
Avorag*
1.6 4.0 3.3 2.0 0.6 0.0
OUCDWION -
Via oanpownrt aaa elaaaad 00 aodtriti1 akla irritant *0*a applied uad! latad to lataut ntlLt uia.
At avaraga --riaua aeoro aao 4*0 out of a poaalbla 6 in t#ontj-four hour**
After m hour thort m alight to *oll-d*f Laod rodaeae for aa avorsgo er* of Li* laflaaaatioa incraaoed in tivtffMr hour* to aUght edaae aad aelldaflaad to eoderat* *rjtb*en.
Aftor rMo*al of tho application, irritation diaialohod to a traco of r*datee la flva 4a?*
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$U MJiaaaarl loaagar Utontwin Csrtltlsats of Analysis - Pmg 8 (2/13/S4) - y-64-7
UBLI V ns IWITAnOH IN MHBIB AITK1I Ar'PLlJATlON OF -TV14V
Saapls (0*1 minuter; Applied Uodilutsd
Agiaal Number
l^Rour
hmrlcil fivaluatlon At Dio
Of
24 Ho^ira 46_dour
Hours 120_Bours
1
22 15
a4
i
21 21 14 *
4
}
22 IS 10 7
l
Average
?`.C
16.0
10.6
6.6
2.0
l6fl_Houra
0 0 0
0.0
DISCUSUN
ft# coapouad *** cliMtd s a ild to aodsrate / irritant.
Ths average saaiaua score
2 3*6 out of possible 110 la on Sour*
Coasidsrable dlscoafort sa# shown iaaadlatsly upon application.
After on* boar there #a aoderate laeriaation, slight edew*, slid to soderete redates of the jwlpebr*.'. conjunctiva*, aild iris congestion, sad slight cornMl dallaese for aa arerag* oeoro of 23.6. Diaeharf* cessed la tveoty-four hours sod acageatioa reducal, loseriag ths average t ^r* to 18.0. Iris sad eoraea were aeraal ia five difo* A slight dsgroo of rednsas oss still preaeat ia too lostaaces.
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HmmiM Cfcealeal m^rnj
It* Uilii Utowi Uberatariee Oortiflcata of Aaalyala - Pag* 9 (2/15/64) - T-64-7
TiUI VI IMUUTICM or ' n-14V VAPCftS ST MATS
Awaraga Taaparatore Inaid# Chaaher ..................................... ............ 79* F. Average ielatiwe daaidlty Inside Chaaher................................... 54 V
Aaouat Of Saaple - To Start...................................... Aeeowerad ................................. Vaporised Or Left la Apparatus............................
150.0 ce 14S.5 eo
1.5 ce (l.M)
ialfkl.No. >Ja
1 - Hal* 2 - Hal* 5 - Mala 4 - Mai*
Survived Survived jU rvivad survived
Soae diaeoafort la tan to fifteea alnataa ... Mild aaaal discharge ... lethargy ...
OccaeionaL shallow breathing ... No weakaeee of consaqaeoce.
DUCUSdlQM -
Ail aaiaele ervi**d to* six hour sxpoeure as wall tha following tao day olMnetioD p*rlc4.
It * o^acludad that tha vapora were slightly toxic uadar ooaditioaa of tha tost.
Inhalation of tho vapors canaad Aoae diacoafort hut tha ajuaals war* not weakened to aay axtaat. Ilo bronchial ralaa or othar an done* of reopirstorj ioflmatioa van aotad either laaediataly following exposure or during the tea day obaarwatioo period.
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