Registration Dossier

Toxicological information

Acute Toxicity: oral

Currently viewing:

Administrative data

Endpoint:
acute toxicity: oral
Type of information:
experimental study
Adequacy of study:
key study
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
comparable to guideline study with acceptable restrictions

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
1974
Report Date:
1974

Materials and methods

Test guideline
Qualifier:
equivalent or similar to
Guideline:
OECD Guideline 401 (Acute Oral Toxicity)
GLP compliance:
no
Test type:
standard acute method
Limit test:
no

Test material

Reference
Name:
Unnamed
Type:
Constituent
Test material form:
solid

Test animals

Species:
rat
Strain:
Sprague-Dawley
Sex:
male/female
Details on test animals and environmental conditions:
TEST ANIMALS
- Source: Gassner
- Weight at study initiation: males: 222 (170 - 252) g; females: 176 (153 - 188) g

ENVIRONMENTAL CONDITIONS
not reported

Administration / exposure

Route of administration:
oral: gavage
Vehicle:
CMC (carboxymethyl cellulose)
Details on oral exposure:
VEHICLE
- Concentration in vehicle: 2 - 30 % aqueous suspension with carboxymethyl cellulose and 2 - 3 drops of Cremophor EL.

MAXIMUM DOSE VOLUME APPLIED: 21.4 mL/kg bw
Doses:
6400; 3200; 1600; 800; 400; 320; 200 mg/kg bw
No. of animals per sex per dose:
5
Control animals:
no
Details on study design:
- Duration of observation period following administration: 7 days
- Frequency of observations and weighing: Body weight was measured on the application day, on day 3 and 4, respectively, and on day 7. Observation of clinical signs was several times on the day of administration and once daily afterwards with the exception of weekends and on holidays.
- Necropsy of survivors performed: yes
Statistics:
Calculation of LD50 by method of Litchfield and Wilcoxon.

Results and discussion

Effect levels
Key result
Sex:
male/female
Dose descriptor:
LD50
Effect level:
685 mg/kg bw
Based on:
test mat.
95% CL:
>= 486 - <= 966
Remarks on result:
other: mortality was observed in doses of 320 mg/kg bw and higher
Mortality:
see table "any other information on results incl. tables"
Clinical signs:
Convulsions, dyspnea, apathy, tremors, salivation, eye discharge, partial exophthalmus, ventral or lateral body position, staggering, exsiccosis, paresis of hind limbs.

6400 and 3200 mg/kg bw:
15 minutes after application convulsions, dyspnea, cower position.
Hours later apathy, tremors, cower position, at 6400 mg/kg bw additionally gasping for breath, partial exophtalmus.
During observation period lateral position, dyspnea, apathy, partially secretion out of eyes and mouth, cower position.

1600 mg/kg bw:
Hours after application dyspnea, cower position, apathy, lateral body position, staggering, clonic convulsions.
Symptoms stable for the following days, additionally tremors and secretion out of mouth and eyes.

800 - 320 mg/kg bw:
Hours after application staggering, partially cower position and creeping, at 800 and 400 mg/kg bw additionally convulsions, latero-abdominal position, dyspnea, aggressiveness, partially weakness of hind limbs, biting convulsions, partially tremors, salivation.
Amelioration of symptoms during the following days, 800 mg/kg additionally exsiccosis.
Animals free of symptoms around day 4.

200 mg/kg bw:
Hours after application cower position, slight apathy.
Animals free of symptoms on day 2.
Body weight:
Body weight gain stagnated during observation period in survivors of all dose groups.
Gross pathology:
Hyperemia, dilatation of heart and gastroesophageal vestibule, fine ulcerations, diarrhoeic intestinal content, discoloration of kidneys and liver in animals that died.
Nothing abnormal found in sacrificed animals.

Any other information on results incl. tables

Mortality 

Dose [mg/kg bw]

Concentration in vehicle [%]

Number of animals and sex

1 h

24 h

48 h

7 d

6400

30

5 M

0/5

5/5

5/5

5/5

 

 

5 F

0/5

5/5

5/5

5/5

3200

30

5 M

0/5

4/5

5/5

5/5

 

 

5 F

0/5

3/5

4/5

5/5

1600

16

5 M

0/5

2/5

2/5

5/5

 

 

5 F

0/5

5/5

5/5

5/5

800

8

5 M

0/5

1/5

1/5

2/5

 

 

5 F

0/5

2/5

4/5

4/5

400

4

5 M

0/5

0/5

0/5

0/5

 

 

5 F

0/5

0/5

1/5

2/5

320

4

5 M

0/5

0/5

0/5

0/5

 

 

5 F

0/5

0/5

1/5

1/5

200

2

5 M

0/5

0/5

0/5

0/5

 

 

5 F

0/5

0/5

0/5

0/5

 

 

Applicant's summary and conclusion

Interpretation of results:
Category 4 based on GHS criteria
Conclusions:
In a study comparable to OECD Guideline 401, the LD50 of the test item was determined to be 685 (95 % CL: 486 - 966) mg/kg bw.
Executive summary:

The acute oral toxicity of the test item was assessed in a study comparable to OECD Guideline 401 (Acute Oral Toxicity, standard acute method). Male and female rats of the Sprague-Dawley strain (weight at study initiation: males: 222 (170 - 252) g; females: 176 (153 - 188) g; number of animals per sex per dose: 5) were exposed by gavage to doses of 6400; 3200; 1600; 800; 400; 320; 200 mg test item/kg bw over a test duration of 7 days. As vehicle carboxymethyl cellulose  (2 - 30 % aqueous suspension with carboxymethyl cellulose and  2 - 3 drops of Cremophor EL) was used. No control was performed. Body weight was measured on the application day, on day 3 and 4,  respectively, and on day 7. Observation of clinical signs was performed several times on the day of administration and once daily afterwards with the exception of weekends and on holidays. In addition, necropsy of survivors was conducted. The LD50 was calculated by method of Litchfield and Wilcoxon.The following clinical signs were observed: Convulsions, dyspnea, apathy, tremors, salivation, eye discharge, partial  exophthalmus, ventral or lateral body position, staggering, exsiccosis,  paresis of hind limbs. At 6400 and 3200 mg/kg bw, 15 minutes after application convulsions, dyspnea and cower position occurred. Hours later apathy, tremors, cower position, at 6400 mg/kg bw  additionally gasping for breath and partial exophtalmus was observed. During observation period lateral position, dyspnea, apathy, partially secretion out of eyes and mouth and cower position was noted. For level of 1600 mg/kg bw, dyspnea, cower position, apathy, lateral body position, staggering and clonic convulsions was reported. The symptoms were stable for the following days (additionally tremors and secretion out of mouth and eyes). At 800 - 320 mg/kg bw, staggering, partially cower position and creeping, at 800 and 400 mg/kg bw additionally convulsions, latero-abdominal position, dyspnea, aggressiveness, partially weakness of hind limbs, biting convulsions, partially tremors and salivation was observed. During the following days all symptoms ameliorated; at 800 mg/kg  additionally exsiccosis occurred. Animals were free of symptoms around day 4. At 200 mg/kg bw, hours after application animals were in cower position and slightly apathic. Animals were free of symptoms on day 2. The body weight gain stagnated during observation period in survivors of all dose groups. By gross pathology, hyperemia, dilatation of heart and gastroesophageal vestibule, fine ulcerations, diarrhoeic intestinal content, discoloration of kidneys and  liver in animals that died was detected. Nothing abnormal was found in sacrificed animals. Mortality was observed in doses of 320 mg/kg bw and higher. In result, the LD50 of the test item was determined to be 685 (95 % CL: 486 - 966) mg/kg bw. Based on this result, the test item is considered to be classified as category 4 based on GHS criteria.