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Toxicological information

Acute Toxicity: oral

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Administrative data

Endpoint:
acute toxicity: oral
Type of information:
experimental study
Adequacy of study:
key study
Study period:
Experimental: 10 Apr 1987 - 25 June 1987
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
other: Comparable to OECD guideline study. Acceptable, well documented report which meets basic scientific principles.

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
1987
Report Date:
1987

Materials and methods

Test guideline
Qualifier:
equivalent or similar to
Guideline:
OECD Guideline 401 (Acute Oral Toxicity)
Version / remarks:
(adopted 1981)
Deviations:
yes
Remarks:
A test group consisting of 5 animals was treated by single gavage application with an aqueous solution of the test substance.
GLP compliance:
no
Test type:
standard acute method
Limit test:
no

Test material

Reference
Name:
Unnamed
Type:
Constituent
Details on test material:
- Name of test material (as cited in study report): Lupragen N 107
- Analytical purity: no data

Test animals

Species:
rat
Strain:
Wistar
Sex:
male/female
Details on test animals and environmental conditions:
TEST ANIMALS
- Source: Dr. K. Thomae GmbH, Germany
- Weight at study initiation: male: 187 g (mean); female: 177 g (mean)
- Fasting period before study: 16 h before administration but water was available ad libitum
- Housing: 5 animals per cage
- Diet: KLIBA-Labordiaet 343, Klingentalmuehle AG, CH, ad libitum
- Water: tap water ad libitum
- Acclimation period: at least 1 week


ENVIRONMENTAL CONDITIONS
- Temperature (°C): 20 - 24 °C
- Humidity (%): 30 - 70 %
- Photoperiod (hrs dark / hrs light): 12/12

Administration / exposure

Route of administration:
oral: gavage
Vehicle:
CMC (carboxymethyl cellulose)
Remarks:
0.5 % aqueous CMC
Details on oral exposure:
VEHICLE
- Concentration in vehicle: 50, 38.3, 21.5, and 10.0 % (w/v), respectively, for 5000, 3830, 2150, and 1000 mg/kg bw doses
- Amount of vehicle (if gavage): 10 mL/kg bw

MAXIMUM DOSE VOLUME APPLIED: 10 mL/kg bw
Doses:
1000, 2150, 3830 and 5000 mg/kg bw
No. of animals per sex per dose:
5 animals/sex/dose
Control animals:
no
Details on study design:
- Duration of observation period following administration: 14 days
- Frequency of observations: recording of signs and symptoms several times on the day of administration, at least once each workday. Check for moribund and dead animals twice each workday and once on holidays.
- Frequency of weighing: days 0, 5, 7, 13
- Necropsy of survivors performed: yes
- Other examinations performed: clinical signs, body weight

Results and discussion

Effect levelsopen allclose all
Sex:
male/female
Dose descriptor:
LD50
Effect level:
>= 2 150 - <= 3 830 mg/kg bw
Based on:
test mat.
Sex:
male
Dose descriptor:
LD50
Effect level:
>= 2 150 - <= 3 830 mg/kg bw
Based on:
test mat.
Sex:
female
Dose descriptor:
LD50
Effect level:
ca. 2 150 mg/kg bw
Based on:
test mat.
Mortality:
See details in "remarks on results".
Clinical signs:
See details in "remarks on results".
Body weight:
Surviving animals gained weight. See details on "remarks on results".
Gross pathology:
- Animals that died:
General congestion.
Stomach/small intestines: mucosa reddened, bloody contents.

- Sacrificed animals:
No pathologic findings noted.

Any other information on results incl. tables

Mortality:

 Dose (mg/kg bw)  Conc.  Gender  1 h  24 h  48 h  day 7  day 14  
 5000 50  male  0/5 5/5 5/5 5/5 5/5  
 5000 50  female  0/5 5/5  5/5  5/5 5/5  
 3830   38.3  male 0/5  5/5  5/5  5/5  5/5  
3830 38.3  female  0/5  5/5 5/5  5/5 5/5  
 2150 21.5  male  0/5  0/5  0/5  0/5 0/5  
 2150  21.5  female  0/5  2/5  2/5  2/5  2/5  
 1000

 10

 male    0/5    0/5    0/5    0/5    0/5  
 1000

 10

 female    0/5    0/5    0/5    0/5    0/5  

Weight (g):

 Dose (mg/kg bw)

 Gender  day 0  day 5  day 7  day 13      
5000  male 92

 -

-    
5000  female 179  - - -    
3830  male 186  - - -    
3830  female 172  - - -    
2150 male  179  - 238 272    
2150  female 179  - 197 215      
1000  male  189  244  -  291      
1000  female  180  205  -  217      

Clinical signs:

Dose (mg/kg bw) 5000 3830 2150     1000
 male  female  male  female  male female  male  female

Dyspnea

1 h - 4 h

 1 h - 4 h

30 m - 5 h

30 m - 5 h 

 1 d - 2 d

 4 h - 2 d

 -

 -

Apathy

 1 h - 4 h

 1 h - 4 h

 30 m - 5 h

 30 m - 5 h 

 1 d - 2 d

 4 h - 2 d

 -

 -

Abnormal position

4 h

4 h

-

4 h - 5 h

 -

 -

 -

 -

Staggering

4 h

4 h

 30 m - 5 h

 30 m - 1 h

 -

 1 d - 2 d

 -

 -

Atonia

 4 h

4 h 

-

4 h - 5 h

 -

 -

 -

 -

Paresis

4 h

4 h

-

4 h - 5 h

 -

 -

 -

 -

Piloerection

  1 h - 4 h

  1 h - 4 h

30 m - 5 h

 30 m - 5 h

 1 d - 2 d

 4 h - 2 d

 -

 -
Cyanosis  4 h 4 h  4 h - 5 h  4 h - 5 h  -  -  -
Exsiccosis 4 h 4 h - 4 h- 5 h  -  -  -  -
Salivation  4 h 4 h - -  -  -  -  -
Poor general state 1 h - 4 h

1 h - 4 h

30 m - 5 h 30 m - 5 h  1 d - 2 d  4 h - 2 d  -  -

min: minutes

h: hour

d: day

The test substance caused systemic toxicity (including mortality) in a dose dependent manner.

Applicant's summary and conclusion