Document r09xnozp63K1q2m86kpwv46r
rr' ' f'U Younger Laboratories
INCORPORATED
QatUuUinf and Analytical Sawicad
CHEMICAL . . . MICROBIOLOGICAL . . . BIOLOGICAL
/on
19S CLIFF CAVI ROAD Saint touts. Mo, eaiao
January 12th, 1972
SUBJECT .
Toxicological Investigation Of: HCS 1228 German Mina Fluid Lot: OR 162483
Monsanto Smsple Number 189 Monsanto Project Number Y-71-189
STUDY CONDUCTED FOR -
Monsanto Company, St. Louis, Missouri
BXFEROBMTAL PROCIDURS -
A) Oral LD)o (Rats, Mlxad Sex) The undiluted compound vsa fed by etomech tube to Spragua-Devley etrein albino male and fsmale rats. After the approxlmste Minimal Lethal Dose was determined, sroups of mala and tamale rata were fed in lncreaslns doses at increments of 0.1 fractional log intervals at four lavals daalgnad to blanket the toxicity range thereby supplying data for calculation of the LDjq which was done acoordlng to the method of R. J. de Baer. Observations were made for toxic signs and the viscera of the test animals were examined nacroscopically. The data are shown in Tabls I.
B) Acuta Skin Absorption Minimal Lethal Dose (Rabbits, Mlxad Sex) The undiluted compound was applied in increasing doses at lncrmsents of 0.2 fractional log intervals to the closely clipped, Intact skin of New Zealand white male and fesmle rabbits. The treated areas were covered with plastic strips and the anlnals held in wooden stocks for periods up to twenty-four hours, after which time they were assigned to individual cages. Observations wars made for toxic signs and the viscera of the test anlnals were examined nacroacoplcally. The data are shown in Table II.
MONS 04459*1
Tot Monsanto Company St. Louie, Mlatourl
Youngar laboratories Certificate of Analyeie - Page 2 (1/12/72) - Y-71-189
EXPERIMENTAL PROCEDURE - (Continued)
C) Skin Irritation (Rabbits, Mixed Sax)
0.5 Milliliter of undiluted sample was applied to the clipped. Intact skin of Mew Zealand white mala and female rabbits under a one inch by ona inch square patch, two alngle layers thick. The patches ware held in place with adhesive tape. The trunk of each anlaal waa wrapped with plastic stripe, to retard evaporation and avoid contamination, for the twenty-four hour exposure period.
Observations were made over a period of seven days for irritation.
The data, scored according to the method of Dralze, Woodard and Calvary (Journal of Pharm. and Exp. Therapeutics, Volume 82, December, 1964) are ehown in Table III.
D) Eye Irritation (Rabbits, Mixed Sex)
0.1 Milliliter of undiluted sample was placed in the conjunctival eac of the right eye of each of three albino male and female rabbits and observations made over a period of seven days for lnflamation. The eyes were rinsed with warm leotonlc saline solution efter the twenty-four hour reading. The left eye served as a control. The data, scored according to the method of Dralze, at al, are ehown in Table TV.
E) Vapor Inhalation (Male Rate) - ambient Temperature
Six mature male rats were placed in a eteinleee steel chamber of 3S-lltera capacity and exposed for alx hours to a concentrated atmosphere of vapors produced by passing a stream of air through 153.5 grama of the compound contained in a 500-mllllllter erlanmeyer flaek. Vapors from the flask passed into a one liter bottle to remove droplets and than into the chamber. Air flow through the sample was 4.0 liters per minute as measured by a calibrated rotameter. This wae sufficient to violently agitate the liquid. Mo supplementary air waa introduced inasmuch as the above eupply wae ample for the animals oxygon requirements. The animals were observed for behavior during exposure and for ten days following exposure. The viscera of the test animals were examined aacroscoplcally.
The data are ehown in Table V.
F) Vapor Inhalation (Male Rate) - Sample Heated to 150C.
Six mature male rata ware placed in a eteinleee steal chamber of 35-llters capacity and exposed for elx hours to a concentrated atmosphere of vapors produced by passing a stream of air through 148.0 grems of the compound contained in a 300-allllllter erlanmeyer flask. The sample was maintained at a temperature of 150C. by lamerelng the flask in a heated tend bath. Vapors from the flask passed into a one liter bottle to remove droplets and then into the chamber. Air flow through the sample wae 4.0 liters per minute as measured by a calibrated rotaawtar. This wae sufficient to violently agitate the liquid. Mo supplementary air wae Introduced inasmuch as the above supply wae ample for the animals oxygen requirements. The animals were observed for behavior during exposure and for ten days following exposure. The viscera of the teet animals were examined mecroscopically.
The data are ehown in Table VI.
MOMS 044595
Tot Moncanto Company
St. Louis, Missouri Younger Leboretortea Certificate of Analysis - Page 3 (1/12/72) - Y-71-189
SUMMARY MCS 1221 German Mina Fluid -- Lott OR 162483
A) Oral LDjq (Rats, Mixad Sax) Tha Oral ID,. for nale and female rata was placed at 12,900 nlllltraaia par kilogram with lower and upper limita of 11,700 to 14,230 allllgrasia per kllogrma. The compound waa claaaed aa practically non-toxic by oral Infection In mala and faaale rate.
B) Acute Skin Absorption Minimal Lethal Dose (Rabbits, Mixed Sex) The Acute Skin Absorption Minimal Lethal Dote for male and female rabbits was found to be greater than 3160 milligrams per kilogram and leaa than 5010 milllgrt par kilogram. The compound waa classed as slightly toxic by skin absorption in mala and female rabbits.
C) Skin Irritation (Rabbits, Mixed Sex) The compound waa classed as non-irrltatlng when applied undiluted to Intact skin of nale end female rabbits. The average maxlanaa score wee 0.3 out of a possible S In twenty-four hours.
D) lya Irritation (Rabbits, Mixed Sex) Tha compound was classed as s slight eye Irritant in male and female rabbits. Tha average maxlanaa score was 12.6 out of a possible 110 In one hour.
S) Vapor Inhalation (Male Rata) - Ambient Temperature All animals survived the six hour exposure as well as the following ten day obaarvatlon period. It wee concouded that the vapors were practically non-toxle under conditions of the test.
F) Vapor Inhalation (Male Rats) Sample Heated to 150C. All animals survived the six hour exposure as well as the following ten day observation period. It was csnaluded that the vapors were practically non-toxic under conditions of tha teat.
YOUNGIR LABORATORIES, INC.
MONS 044596
tot Monsanto Coapany St. Louis, Mlaaouri
Younger Laboratorieo Certificate of Analysis - Page 4 (1/12/72) - Y-71-189
fOX
TABLE I THE ORAL LD ,0 OF 'IKS 1228 Qeraaa Hina nuid .. Lot: OB 162483'
>0B BATS Saapla rod Undiluted
Anlaal Bo. - Sea
Weight 0a.
Dose Mg. /Kg.
Fata
1-- reaals 2- Male > Feanle 4- Mala 5- resale
6- Mule 7- Feaale 8- Nila 9- Feaale 10- Mala
11- resale 12- Male 13- resale 14- Male 15- Feaale
16- Mule 17- resale l8- Ifcle 19- resale 20- Male
225 7,940 225 7,940 225 7,940
240 7,940 215 7,940
225 10,000 205 10,000 235 10,000 250 10,000 215 10,000
245 12,600 205 12,600 225 12,600 230 12,600 240 12,600
205 15,800 210 15,800 220 15,800 240 15,800 265 15.800
Survived Survived Survived Survived Survived
Survived Survived Survived
Died Survived
Survived Died Died
Survived Surrlwd
Died Died Survived Died Died
DISCUSSION -
She Oral LD50 for aala and fenale rata ana placed at 12,900 allligraas per kilogram with lower and upper Unite of 11,700 to 14,230 milligram* per kilograa.
the ooapoaad ana elaaaed aa practically non-toaic by oral iageetioa in aala and feaale rata.
arrival tiae uaa tour to aiz daye. Seale aigna included redueed appetite and activity (two to five days in survivors), lnsreaalag weakaeaa, eollapaa, and death.
At autopay there was alight Uver discoloration and gastrolateetlaal laflaaaatloa.
Surviving aalaals were aacrlfleed eavan days after dosing. The viscera appeared aoraal by aacroaaopic sveai nation.
HONS 04459 7
Tot Neaeanto Ceapaay It. Louis, Niaaourl
Toanger Laboratories Certificate of Analyst* . Pago 5 (1/12/72) - T.71-189
TABU II
TIB ACUTE SKIN AISOVtlOH MINIMAL LXTBAL DOSI OF MBS USB Ooxaaa Hu Fluid -- Uti OR 162683' FOR RABBITS
laapl* Applied Undiluted
Aalaal So. - Sex
1 - Feaale 2 - Hal* 3 . Feaale 6 - Halo 5 - Feaale 6 - Ihl*
Weight Jfc-
2.7 2.5 2.7 2.6 2.0 2.6
Doe* -/-
1260 2000 3160 3010 7960 7960
4-
0
1
Weight Chang* 5 Days later ____ **
+ 0.1 0.0
- 0.6 - 0.6 - 0.6
Fate
Survived Survived Survived Died - 16 Says Died - U Soya Died - 12 Soya
DISCUSSION .
The Acat* Skin Abaorptlon Mlnlaal Lstbal Daoa for aal* and foaal* rabbita was feud to bo groatar than 3160 ajlligraas par kilograa and laaa than SO10 ailllgraw par kilograa. Iha compound was olaaaod as slightly toxin by akin abaorptlon la aal* aad foasis rabbito.
Survival tla* waa alawan to fourteen days. Taxis signs iaclndad reduced appetite aad activity (thro* to asaaa toy* in auralaara), iaoraaalng waakaaaa, oollapaa, and daath.
At autopay thara was haaarrbaglc areas of the lungs, discolored liver (nettled and Jaundiced), enlarged gall bladder, and putrointestinal tract was gaseous and iaflaaaed.
Surviving anlaala were sacrificed fourteen days after dosi^. The viscera of aaitola #1 aad #2 appeared nornal by uceroaoople exaalnation; anlaal #3 chawed liver hypereala.
HONS 0`ti*598
Tot Monsanto Ceapan; St. Louis, Mlaaourl
Younger Laboratories Certificate of Analysis - Page 6 (1/12/72) - Y-71-189
T A B L I III
skim ibbitatxom a babbits arm application op
'MCS 1228 Canaan Hina Fluid--Lot: OB 162483'
Saaple (0.3 Mlllllitar) Applied Undiluted
Numerical Evaluation At The End Of Anlaaljlo.-_lu l_8our 24_Hours 48_Hours 72_Hours 120 Hours
168 Hours
1 Mala
0
0
0
0
0
0
2 . Paula
0
1
1
0
0
0
3 - Mala
0
0
0
0
0
0
Average 0.0 0.3 0.3 0.0 0.0 0.0
DISCUSSION The compound was elaaaad as non-lrrltatlng whan applied undiluted to Intact skin of nale and festala rabbits. The average saxisui score was 0.3 out of a possible 8 In tvanty-four hours.
Observations following application -
1-Hour 24-Hourst 48-Hoursi 72-Hours< 120- 168-Hours:
Ho skin changes; zero readings Tory alight erythana In ana Instance; no adana Vary slight erytheau In one Instance; no edaaa No erytheaa or sdaoa; zaro readings No arytheoa or adana; zero readings
The ntst-M in 1KU
i* to V'
the p
tuav ..-n ). v. n l.......
s*v.:rcc nl ti-w I**"*
!: ! >>''' I;;;/,,;,-
i.out tl I n... J-;
-The i,-. ;i .vnonr*
' \ rulo
i>r.> -----. .,- I>f
^, .*
meet in Si. Loci lor ispiy -- Monsanto Company
M0NS 044599
ToI Monsanto Company It. Louis. Missouri
Younger Laboratories Certificate of Analysis - Page 7 (1/12/72) - Y-71-189
TAILS IV
ITS IRRITATION IN BABBITS APRS APPLICATION OP 'MCS 1228 Ganan Mina Fluid --Lot: OR 1*2483'
Sample (0.1 Mlllllltar) Applied Undiluted
Animal
Nuaierlcal Evaluation At The Snd Of Sex l.Hour 24_Hours 48 fours 72_Houra 120_Houra
16S_Hours
1 - Mala 12 2 0 0 0 0
2 Panala
14
2
0
0
0
0
3 - Male 12 2 0 0 0 0
Average
12.6
2.0
0.0
0.0
0.0 0.0
DISCUSSION -
The compound was classed as a alight eye Irritant In aals and finale rabbits. The average naxlmun score was 12.6 out of a possible 110 In one hour.
Observations following application --
Inaadlate: 10-Minutes:
1-Hour:
24-Hours: 48-Hours: 72- 1*8-Hours:
Discomfort was slight Slight arytheau and adana, moderate discharge Slight to noderate arythana, slight adana, copious discharge Slight arythana; no adana or discharge No arythana, ednaa, or discharge; zero readings No arythana, adana, or dlacharga; zero readings
HONS 044600
Toi Haaiawto Coopany St. MH, Mleeourl
Younger Laberatorlaa Cartlflcata et lulyala - Page 8 (1/12/72) . T-71-189
mu v
auuxvm at 'MB! 1228 tana Mima Plaid -- Bt CKi 1(2483' VAPOBJ
n UTS (4WISMT TWPDUIUU)
Average Ta^aratora laalda Chaaber....................................... drama Relative laaldltp laalda Buatir ..............
lawat of Sapla
>4 atart.........................153.3 Ormm Recovered....................... 153.5 Oran Vaporlaad ar laft
la equlpaMat............. 0.0 Oral
(0.0 X)
Average Coacaatratlaa of Papera la Chaaber 0.0 Graa/N^
74 p. 7| x
Aalaal Bo. - Sex
1 Hale 2 - Mala 3 - Mala 4 - Mala 5 - Mala ( - Male
Pata
turvlved Survived Survived Survived Survived arrived
Obearvatloee Durlay Izpoeare
Bo aaaal or ocular dlacharge ... Me veakaaaa or drovalaaee af eaniftqonci leeplratlon appeared aeraal.
BIS0USS1CM -
All aalaela aaralpad the alx bear expoeure aa wall aa the felloelad tee day obeervatleo period.
It oaa aaacladad that tha vapora aara practically non-toalc under caadltloaa at the teat.
Obeervatleae lellovlng expoeuro . Raaplratlaa aaa aeraal ahaa aalaala aara raoovad free tha chaaber. Tha taa dap obearvatlea period aaa uneventful. Height gain aaa normal.
Sarrlalag aalaala aara aacrlllcad taa dapa alter axpoaura. Tha vlaeara appeared aaraal bp aacroacoplc asaalnatloa.
/A
MONS 044601
Toi Manunto Co^ini (t. U*li, Mlaeourl
TouBfer Laboratories Cartllleata of Analysis - Pas 9 (1/12/72) - 1-71-189
III l I 91
women or MC8 1228 Ooraaa Mlaa fluid -- Lot] CM 162483' VtfOU
81 UTf (HUTU 888X88 TO 130 f.)
Average Taaperatare Iaslde Chaahor ....................... Average Kelatlve kaUltj laalda Cbaahsr....................... ..
78 T. 83 X
(want of tafli -- To atart .......................
146.0 Oraaa
lecovered ............... 140.8 Srm
Total Vaporised................. 5.2 Oraaa (3.6 t)
Bacavered fraa Coadaaaer. 0.7 Otaa (0.5 X)
MalfM of vapora aatorlBg
chaakar............................. 4.3 Orau (3.1 X)
Avarags Concentration Of Vapora la Chaakar .. 3.12 Oraaa / M3
8a. - 8ax
Mala > Mala ' Mala Mala > Mala
Mala
fata
(arrived (arrived (arrived (arrived (arrived (arrived
Observations Barlaa lapoaata
Bo aaaal or ocular dlacharge ... Me aaakaaae or droaalaaae of CMMquaacft leaplratloa appaarad aoraal.
8X86088108 -
All anlaala survived tha alx hoar exposure aa wall aa tha follavlaa toa day observation patlad. It uaa eaaelndad that tha vapors vara practically non-toxic undar coadltloaa of tha taat.
Observations follaalaa oapeoure taaplzatlaa aaa novas! ahan aalaala aara reaovod fraa tha chaabar. Tha taa day abaarratlon parlod aaa aaaaantfal. Walaht pain aaa aoraal.
(arriving aalaala aara aacrlficad taa daya after expoeura. Tha alacara appaarad aoraal by aacroicoplc aipdutla.
MOWS 04460*