Registration Dossier

Administrative data

Endpoint:
acute toxicity: other routes
Type of information:
experimental study
Adequacy of study:
key study
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
other: Study meets generally accepted scientific principles.

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
1982
Report Date:
1982

Materials and methods

Principles of method if other than guideline:
BASF-Test:
The substance was injected into the peritoneal cavity. Young adult laboratory mice were purchased from breeder. Several groups of 5 mice per sex and dose were treated simultaneously with preparations of the test substance in suitable vehicle. The concentrations of these preparations were used to achieve comparable volumes per kg body weight. Group-wise documentation of clinical signs was performed over the 14 day study period.
GLP compliance:
no
Remarks:
GLP was not compulsory at the time the study was conducted
Limit test:
no

Test material

Reference
Name:
Unnamed
Type:
Constituent
Details on test material:
- Stable until: 81/171: October 1981; 81/171-1: June 1982

Test animals

Species:
mouse
Strain:
NMRI
Sex:
male/female
Details on test animals and environmental conditions:
TEST ANIMALS
- Source: Charles River Wiga, Sulzfeld, Germany
- Age at study initiation: About 4 weeks
- Weight at study initiation: mean males: 25 g; mean females: 23 g
- Fasting period before study: Feed was withdrawn from the animals 16 hours before administration, but water was available ad libitum
- Housing: Type I Makrolon cages; 5 animals per cage
- Diet (e.g. ad libitum): SSNIFF R; supplied by SSNIFF, maintenance diet; D-W4470 Soest, Germany
- Water: Fully demineralized water each workday, ad libitum; tap water on public holidays, ad libitum
- Acclimation period: at least one week

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 20 - 26°C
- Humidity (%): 45 - 75%
- Photoperiod (hrs dark / hrs light): 12 / 12 (6.00 p.m. - 6.00 a.m. dark; 6.00 a.m. - 6.00 p.m. light)

Administration / exposure

Route of administration:
intraperitoneal
Vehicle:
water
Details on exposure:
The substance was injected into the peritoneal cavity. The administration volume was 10 ml/kg.
Doses:
200, 100, 68.1 mg/kg bw
No. of animals per sex per dose:
5 males and 5 females per dose
Control animals:
no
Details on study design:
- Duration of observation period following administration: 14 days
- Frequency of observations and weighing: Weight check at beginning of test and after 4 d, 7 d and 13 d. Recording of signs < 15 min, 15 min, 30 min, 1 h, 2 h, 4 h and 5 h after administration of test substance, then each workday. Check for moribund and dead animals twice each workday and once daily on weekends and public holidays.
- Necropsy of survivors performed: yes
- Other examinations performed: clinical signs, body weight,organ weights, histopathology, other:

Results and discussion

Effect levelsopen allclose all
Sex:
male/female
Dose descriptor:
LD50
Effect level:
ca. 100 mg/kg bw
Sex:
male
Dose descriptor:
LD50
Effect level:
ca. 120 mg/kg bw
Remarks on result:
other: value from interpolation
Sex:
female
Dose descriptor:
LD50
Effect level:
ca. 100 mg/kg bw
Mortality:
At the highest dose tested all animals died within the first day. At 100 mg/kg 1 male and 3 females died one day after application; no mortalities occurred at 68.1 mg/kg. For details see table below.
Clinical signs:
Signs of intoxication at 200 mg/kg: dyspnea, apathy, staggering, paresis of hind limb, trembling, ruffled fur and poor general state (4 - 5 h after application); 100 mg/kg: dyspnea, apathy, ruffled fur and poor general state (4 h - 1 d after application); at concentrations of 68.1 mg/kg no signs of intoxication were observed.
Body weight:
For details see table below.
Gross pathology:
Animals that died (male + female): At 100 mg/kg: liver: despite congestion individual greyish brown areas to be seen also on the cut surface. At 200 mg/kg: no intraabdominal conglutinations or test substance deposits.
Sacrificed animals (male + female): organs found to be normal.

Any other information on results incl. tables

 Mortality and body weight:

Dose (mg/kg)

200.0

100.0

68.1

 

Dead males after:

 

 

 

1 h

0/5

0/5

0/5

1 d

5/5

1/5

0/5

2 d

5/5

1/5

0/5

7 d

5/5

1/5

0/5

14 d

5/5

1/5

0/5

 

Dead females after:

1 h

0/5

0/5

0/5

1 d

5/5

3/5

0/5

2 d

5/5

3/5

0/5

7 d

5/5

3/5

0/5

14 d

5/5

3/5

0/5

 

Mean weight males (g):

Beginning of test

26.0

26.0

23.0

4 d

 

32.3

30.2

7 d

 

34.5

32.2

13 d

 

37.0

35.4

 

Mean weight females (g):

Beginning of test

22.0

24.0

24.0

4 d

 

25.5

28.4

7 d

 

27.5

28.2

13 d

 

29.5

28.2

 

Applicant's summary and conclusion

Conclusions:
Under the test conditions the LD50 after i.p. application in mice is approx. 120 mg/kg bw for males, approx. 100 mg/kg bw for females and approx. 100 mg/kg bw for males and females.
Executive summary:

The study meets generally accepted scientific principles.

Groups of 5 mice per sex and dose were treated with preparations of the test substance in water. The substance was injected into the peritoneal cavity at 200, 100 and 68.1 mg/kg bw. The application volume was 10 ml/kg bw. A 14 -day observation period followed the application of the test substance.

At the highest dose tested all animals died within the first day. At 100 mg/kg 1 male and 3 females died one day after application. No mortalities occurred at 68.1 mg/kg. Signs of intoxication at 200 mg/kg were dyspnea, apathy, staggering, paresis of hind limb, trembling, ruffled fur and poor general state (4 - 5 h after application). At 100 mg/kg clinical signs were dyspnea, apathy, ruffled fur and poor general state (4 h - 1 d after application). At 68.1 mg/kg no signs of intoxication were observed. Gross pathologic findings of animals that died were at 100 mg/kg despite congestion individual greyish brown areas in the liver to be seen also on the cut surface. At 200 mg/kg no intraabdominal conglutinations or test substance deposits were found. In sacrificed animals organs were found to be normal.

Conclusions: Under the test conditions the LD50 after i.p. application in mice is approx. 120 mg/kg bw for males, approx. 100 mg/kg bw for females and approx. 100 mg/kg bw for males and females.