f l

• ' s Toxicolog y GU2. 1 1/ 9

REPOR T O

N ACUT E ORA L LD IN ' TH E RAT O F T K 1 2^+4 3 A'^^' ^ Z3< ^ 5 0 Projec t No . : Sponsor : 78496 5

Tes t materia l received ; Batc hNo.: . Physica l appearance : Augus t 2 , 197 8 A16-234/ 5 soli d
Th e experimen t wa s carrie d ou t betwee nSeptembe r 9 , and Octobe r 31 , 197 8 Studydirector ; Approve d by :
Reporte d and archivated : Decembe r 21 , 1978/wu ; This document is directed to USEPA pursuant the Toxic Substances Control Act (TSCA). This document is the property of the sponsor and may be used only for that purpose intended by the sponsor and as authorized under applicable law. Every other or additional use, exploitation, reproduction, publication or submission to other parties requires the written permission of the sponsor, except as otherwise required by applicable law (e.g., TSCA). The use of these studies/documents for regulatory, registration or other commercial purposes [including but not limited to Registration, Evaluation, Authorization and Restriction of Chemical Substances (REACH)], without the express written permission of the sponsor is unauthorized and strictly prohibited.Toxicolog y

G U2. 1 2/ 9 78496 5

Summar yan d Conclusio n Th e acut e ora l LDS O o f T K 1244 3 i nrat s o f bot hsexe s observe d ove r a perio d o f 1 4 day s i s greate r tha n775 0 mg/kg , Th e tes t materia l ha s therefor e practicall yn o acut e toxicit yt o th e ra t bythi s rout e o f administration . Metho d
, Volum e (ml/kg ) Concentration : Vehicle : 1 0 - 25. 8 10 , 20 , 3 0 % polyethylen e glycol - (PE G400 ) a ) Tes t materia l an d formulatio n T K 1244 3 was'suspended . Befor e treatmen t th e Suspensio n wa s homogeneousl ydisperse d wit ha nUltra-Turra xan d durin g treatmen t i t wa s kep t stabl e wit ha magneti c stirrer . b ) Animal s Healthyrando m

bre d rat s o f th e Tif:RAI f (SPF ) strai n ( 7 t o 8 week s old ) raise d o nth e premise s wer e use d fo r thes e experiments . The ywer e kep t a t a roo m temperatur e o f 2 2 + 1 ° C , a t a relativ e humidit y o f 5 5 + 5 % and o na 1 0 hour s ligh t cycl e day . The yreceive d a d libitumra t foo d - NAFAG , Gossa u S G- an d water . Prio r t o treatmen t th e animal s wer e adapte d t o ou r laboratorie s fo r a minimu mo f 4 days . Bodyweight s wer e recorde d immediatel y prio r t o dosin g (contro l weights ) an d a t 7 an d 1 4 day s (Tabl e 2) .Toxicolog y

GU2. 1 3/ 9 78496 5 c ) Treatmen t an d observation s Durin g th e treatmen t an d observatio nperio d th e animal s wer e house d i ngroup s o f 5 i nMacrolo n cage s (typ e 3) . Animal s faste d overnigh t wer e treate d byora l intubation . Physica l conditio nan d rat e o f death s wer e monitore d throughou t th e whol e observatio n period . 3 . Result s a ) Rat e o f death s Tabl e 1 b ) Bodyweigh t chang e Tabl e 2 c ) Sign s an d symptom s Table s 3 t o 6 Th e animal s recovere d withi n9 t o 1 1 days . The y wer e submitte d a t rando mt o a necrops ya t th e en d o f th e observatio nperiod . ,d ) Autopsie s Kille d Animal s N o substanc e relate d gros s orga n change s wer e seen .Tabl e1 

### ?-v? ^ 9 (o 5

RAT E Dos e mg/k g : OFC

S e x )EATH S Tota l Numbe r animal s i ngrou f Tota l

Numbe r animal s dea d Deat h

rat e percen - tag e rt f

1 H < f p r 2 Dur s d o s 4 in g 8 2 4 Ti n

2 l eo 3 f d e • ^ 4 a t h 5 a f t 6 e r c Day s 7 o s i a f 8 a g t e r 9 d o s 1 0 i n g 1 1 1 2

•'•'• • •'•• r 1 3 1 4 

## ./IOO O 2/15 0 

# ^h m ??5 0 

# x 

# s 5

5 5 5 0 0 0 0 0 0 0 0
' 

## ylOO O 2./i5Q > 

# ^b % •^5 0 ^ • 

## c s 

# ? 5 5 5 5 0 0 0 0 0 0 0 0 - •



## ^/^ O hkhe r

o/o£e s JiJ^y ^fz^ossjhld . x> . "v , V£>

### Toxicolog

y G U2. 1 

## ^ S ^ 3(o S Tabl e 2

Da y1 Da y1 Da y7 Da y7 Da y1 4 Da y1 4 (

^ o -1 - 6 

## ? 6 

## ? MEA

N BODYWEIGHT/S D (g ) 

## AOO O

AU I kj \ Am i l^ J 25A I 1 9 ..h l(Oth ,«/ , 

## ZAS O Al-i / /2. 3 

# A^y' 233 / ZAbI Ibi l lAA.I^ 

## 239 / Dos e(m

c 

# 44 W A'^S / /3- > /11-5/ 

## hi Z 240 1 2S3 / j/kg )



### l-T-S O AU I \A.( C 

### A(,3 / I.Ai 2 kl( p 

# W l 11 ^

c n

### Toxicolog

y G U2. 1 

## ^sq-a6 5 Tabl e 3 " Sign s Sign s an d symptom s Sedatio n Dyspnoe a Dacryorrhoe a Chromodacryorrhoe a Rinorrhoe a Epistaxi s Exophthalmo s Salivatio n Ruffle d fur Pallo r Cyanosi s Diarrhoe a Bod ypositio n(ventral ) Bod ypositio n(lateral ) Bod ypositio n(curved ) Ataxi a Trismu s Tremo r Toni c cloni c muscl e spasm s Convulsion s an d Hour s 1 

### • f 

## +

+ 4 -



## + sym p 3 2 

### + -

- h



## + 4 -

• + tom s
4 

### -1 -
• h



## +

4 -

- 

## 6 2 4 

## • f •f -



## +

4 - Da y 2 . 

## +

+

+ s 3 . 4 . 5 .



### - f



## + -

i - ~ 6 .

• f

• f



### 4 - D o
7 .

• h



### 4 -



### 4

. s e ( n
8 . ig/k g 9 . ) : 10 . 

# ^ 0 11 . 

# 0 0
12 . 13 . 14 .Toxicolog y G U2. 1 

## -l^H-9^s Tabl e Lj . - Sign s Sign s and symptom s Sedatio n Dyspnoe a Dacryorrhoe a Chromodacryorrhoe a Rinorrhoe a Epistaxi s Exophthalmo s Salivatio n Ruffle d fur Pallo r Cyanosi s Diarrhoe a Bod ypositio n(ventral ) Bod ypositio n(lateral ) Bod ypositio n(curved ) Ataxi a Trismu s Tremo r Toni c cloni c muscl e spasm s Convulsion s . an d Hour s 1 

### 4 - 4 -
-j - 

# +



# + sym p
3 2 

# + •4 -


### 4- 4 -



### 4 - tom s 4 

### • f 4 -

4 -

4 - 

## 6 2 4



### • f 4 -

4 -

4 - Day 2 . 

### 4 - 4 -

4 -

4 -

^ s 3 . 

### 4 - •f

I . 

# +

4 - 4 . 

# + 4 -

4 -

4 - 5 . - 6 . 1 D C

7 . 

### f1-

f h s e (

n 8 . 

# +

4 -

• f ag/kg 9 . 

### 4 -



### 4 -

4 - ) : - 10 . 

## ^.4 f 1 1 . 

### )- 0 12 . 13 .

' 14 .Toxicolog y

G U2. 1 

## ^ S 4-6(^ 5 Tabl e - Sign s Sign s and symptom s Sedatio n Dyspnoe a Dacryorrhoe a Chromodacryorrhoe a Rinorrhoe a Epistaxi s Exophthalmo s Salivatio n Ruffle d fur Pallo r Cyanosi s Diarrhoe a Bod ypositio n(ventral ) Bod ypositio n(lateral ) Bod ypositio n(curved ) Ataxi a Trismu s Tremo r Toni c cloni c muscl e spasm s Convulsion s . an d Hour s 1 

## 4- 4 -
4 - 4 -

4 -

- sym p
3 2 

### 4 - 4 -


### 4 - 4 -



## • f tom s 4 

## 6 2 4



### 4 - 4 -



## + +

4 - Day 2 . 

### 4 - 4 -

4 - 

### 4 -

4 - s 3 . 

### 4 -
4 - 

# +

+ 4 . 

## f

•+ -



## 4 5 . \ 6 . D C

7 . 

### 4 -

4 -

+ - s e (r 8 . 4 -



### 4 -

4 - ng/kg 9 . 

## 4

4

4 ) : 10 . 

# 4-6 ^ 1 1 . ) 12 . 13 .

' 14 .Toxicolog y

GU 2. 1 

## 7S496 5 Tabl e ( > - Sign s Sign s an d symptom s Sedatio n Dyspnoe a Dacryorrhoe a Chromodacryorrhoe a Rinorrhoe a Epistaxi s Exophthalmo s Salivatio n Ruffle d fur Pallo r Cyanosi s Diarrhoe a Bod ypositio n(ventral ) Bod ypositio n(lateral ) Bod ypositio n(curved ) Ataxi a Trismu s Tremo r Toni c cloni c muscl e spasm s Convulsion s > an d Hour s 1 •4 - 

## 4 -
4 - 

## + 4 - 

## 4 sym p 3 2 

## 4 - 

## 4
4 - 

## 4 4 - 

## 4 tom s 4 

## 6 2 4

•4 -

- h


## 4 - 4 - 

## 4 4 Da y 2 . 

## 4 - 

## +
4 - 4 - 4 - 

## f s 3 . 4 . 5 .



## 4

4 -

4 - 6 . 

## 4

4-



## 4 D o 7 . 

## f

f

f s e ( r 8 . ng/kg 9 . ) : 10 . 

## >-^ 5 11 . 

## 0 12 . 13 .

* •
14 .

v o

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