fl 

• 's 

Toxicology 

GU 2.1 

1/9 

REPORT ON 

ACUTE ORAL LD IN' THE RAT OF TK 1 2^+43 A '^^' ^ Z3<^ 

50 

Project No. : 

Sponsor: 

784965 

Test material received; 

Batch No.:. 

Physical appearance: 

August 2, 1978 

A 16-234/5 

solid 

The experiment was carried out between September 9, and 

October 31, 1978 

Study director; 

Approved by: 

Reported and archivated: December 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.
Toxicology 

GU 2.1 

2/9 

784965 

Summary and Conclusion 

The acute oral LDSO of TK 12443 in rats of both sexes 

observed over a period of 14 days is greater than 7750 mg/kg, 

The test material has therefore practically no acute 

toxicity to the rat by this route of administration. 

Method 

, Volume (ml/kg) 

Concentration: 

Vehicle: 

10 - 25.8 

10, 20, 30 % 

polyethylene glycol- (PEG 400) 

a) Test material and formulation 

TK 12443 was'suspended. Before treatment the Suspension 

was homogeneously dispersed with an Ultra-Turrax and 

during treatment it was kept stable with a magnetic 

stirrer. 

b) Animals 

Healthy random bred rats of the Tif:RAIf (SPF) strain 

(7 to 8 weeks old) raised on the premises were used 

for these experiments. They were kept at a room 

temperature of 22 + 1° C, at a relative humidity 

of 55 + 5 % and on a 10 hours light cycle day. 

They received ad libitum rat food - NAFAG, Gossau SG -

and water. Prior to treatment the animals were 

adapted to our laboratories for a minimum of 

4 days. Bodyweights were recorded immediately 

prior to dosing (control weights) and at 7 and 

14 days (Table 2). 
Toxicology 

GU 2.1 

3/9 

784965 

c) Treatment and observations 

During the treatment and observation period the 

animals were housed in groups of 5 in Macrolon 

cages (type 3). 

Animals fasted overnight were treated by oral 

intubation. Physical condition and rate of deaths 

were monitored throughout the whole observation 

period. 

3. Results 

a) Rate of deaths Table 1 

b) Bodyweight change Table 2 

c) Signs and symptoms Tables 3 to 6 

The animals recovered within 9 to 11 days. They 

were submitted at random to a necropsy at the end 

of the observation period. 

,d) Autopsies 

Killed Animals No substance related gross organ 

changes were seen. 
Tabl e 1 ?-v? ^9 (o5 

RATE 

Dos e 

mg/k g 

: OF C 

S e x 

)EATHS 

Tota l 

Number 

animals 

i n grou f 

Tota l 

Number 

animals 

dea d 

Deat h 

rat e 

percen -

tag e 

rtf 

1 

H< 

f p r 

2 

Durs 

d o s 

4 

i ng 

8 24 

Tin 

2 

le o 

3 

f de 

•^ 

4 

a t h 

5 

a f t 

6 

e r c 

Days 

7 

o s i 

a f 

8 

ag 

t e r 

9 

d o s 

10 

i n g 

11 12 

•'•'•• •'•• r 

13 14 

./IOOO 

2/150 

^hm 

??50 

x 

s 

5 

5 

5 

5 

0 

0 

0 

0 

0 

0 

0 

0 

' 

ylOOO 

2./i5Q> 

^b% 

•^50 

^ 

• 

cs ? 

5 

5 

5 

5 

0 

0 

0 

0 

0 

0 

0 

0 -

• 

^ /^O hkhe r o/o£es JiJ^y^ fz^ossjhld. 

x>. 

"v, 

V£> 
Toxicology 

GU 2.1 

^S ^3 (oS 

Table 2 

Day 1 

Day 1 

Day 7 

Day 7 

Day 14 

Day 14 

(^ 

o 

-1-

6 

? 

6 

? 

MEAN 

BODYWEIGHT/SD 

(g) 

AOOO 

AUI 

kj\ 

Ami 

l^J 

25AI 

19 ..h 

l(Oth 

,«/ , 

ZASO 

Al-i/ 

/2.3 

A^y' 

233/ 

ZAbI 

Ibil 

lAA.I^ 

239/ 

Dos e (mc 

44 W 

A'^S/ 

/3-> 

/11-5/ 

hiZ 

2401 

2S3/ 

j/kg ) 

l-T-SO 

AUI 

\A.(C 

A (,3/ 

I.Ai2 

kl(p 

Wl 

11^ 

cn 
Toxicology 

GU 2.1 ^sq-a65 

Table 3 " Signs 

Signs and symptoms 

Sedation 

Dyspnoea 

Dacryorrhoea 

Chromodacryorrhoea 

Rinorrhoea 

Epistaxis 

Exophthalmos 

Salivation 

Ruffled fur 

Pallor 

Cyanosis 

Diarrhoea 

Body position (ventral) 

Body position (lateral) 

Body position (curved) 

Ataxia 

Trismus 

Tremor 

Tonic clonic muscle spasms 

Convulsions 

and 

Hours 

1 

•f 

+ 

+ 

4-

+ 

symp 

3 

2 

+-

-h 

+ 

4-

•+ 

toms 

4 

-1-

•h 

+ 

4-

-

6 24 

•f 

•f-

+ 

4-

Day 

2. 

+ 

+ 

+ 

s 

3. 4. 5. 

-f 

+-

i-

~ 

6. 

•f 

•f 

4-

Do 

7. 

•h 

4-

4 

. 

se (n 

8. 

ig/kg 

9. 

) : 

10. 

^0 

11. 

00 

12. 13. 14. 
Toxicology 

GU 2.1 -l^H-9^sTable Lj. - Signs 

Signs and symptoms 

Sedation 

Dyspnoea 

Dacryorrhoea 

Chromodacryorrhoea 

Rinorrhoea 

Epistaxis 

Exophthalmos 

Salivation 

Ruffled fur 

Pallor 

Cyanosis 

Diarrhoea 

Body position (ventral) 

Body position (lateral) 

Body position (curved) 

Ataxia 

Trismus 

Tremor 

Tonic clonic muscle spasms 

Convulsions 

. and 

Hours 

1 

4-

4-

-j-

+ 

+ 

symp 

3 

2 

+ 

•4-

4-

4-

4-

toms 

4 

•f 

4-

4-

4-

6 24 

•f 

4-

4-

4-

Day 

2. 

4-

4-

4-

4-

^ 

s 

3. 

4-

•f 

I. 

+ 

4-

4. 

+ 

4-

4-

4-

5. 

-

6. 

1 

DC 

7. 

f1-

fh 

se (n 

8. 

+ 

4-

•f 

ag/kg 

9. 

4-

4-

4-

) : -

10. 

^.4f 

1 1 . 

)-0 

12. 13. 

' 

14. 
Toxicology 

GU 2. 1 

^S 4-6(^5 

Table - Signs 

Signs and symptoms 

Sedation 

Dyspnoea 

Dacryorrhoea 

Chromodacryorrhoea 

Rinorrhoea 

Epistaxis 

Exophthalmos 

Salivation 

Ruffled fur 

Pallor 

Cyanosis 

Diarrhoea 

Body position (ventral) 

Body position (lateral) 

Body position (curved) 

Ataxia 

Trismus 

Tremor 

Tonic clonic muscle spasms 

Convulsions 

. and 

Hours 

1 

4-

4-

4-

4-

4-

-

symp 

3 

2 

4-

4-

4-

4-

•f 

toms 

4 6 24 

4-

4-

+ 

+ 

4-

Day 

2. 

4-

4-

4-

4-

4-

s 

3. 

4-

4-

+ 

+ 

4. 

f 

•+-

4 

5. 

\ 

6. 

DC 

7. 

4-

4-

+-

se (r 

8. 

4-

4-

4-

ng/kg 

9. 

4 

4 

4 

) : 

10. 

4-6 ^ 

1 1 . 

) 

12. 13. 

' 

14. 
Toxicolog y 

GU 2. 1 7S4965 

Table (> - Signs 

Signs and symptoms 

Sedation 

Dyspnoea 

Dacryorrhoea 

Chromodacryorrhoea 

Rinorrhoea 

Epistaxis 

Exophthalmos 

Salivation 

Ruffled fur 

Pallor 

Cyanosis 

Diarrhoea 

Body position (ventral) 

Body position (lateral) 

Body position (curved) 

Ataxia 

Trismus 

Tremor 

Tonic clonic muscle spasms 

Convulsions 

> and 

Hours 

1 

•4-

4-

4-

+ 

4-

4 

symp 

3 

2 

4-

4 

4-

4 

4-

4 

toms 

4 6 24 

•4-

-h 

4-

4-

4 

4 

Day 

2. 

4-

+ 

4-

4-

4-

f 

s 

3. 4. 5. 

4 

4-

4-

6. 

4 

4-

4 

Do 

7. 

f 

f 

f 

se (r 

8. 

ng/kg 

9. 

) : 

10. 

>-^5 

11. 

0 

12. 13. 

* 

• 

14. 

vo 

VO 
^^