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Administrative data

Description of key information

The oral LD50 value was determined to be > 2000 mg/kg bw in rats.

Key value for chemical safety assessment

Acute toxicity: via oral route

Link to relevant study records

Referenceopen allclose all

Endpoint:
acute toxicity: oral
Type of information:
experimental study
Adequacy of study:
weight of evidence
Study period:
1992-01-15 to 1992-02-05
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
guideline study
Reference:
Composition 0
Qualifier:
according to
Guideline:
OECD Guideline 401 (Acute Oral Toxicity)
Version / remarks:
1981
Deviations:
no
Qualifier:
according to
Guideline:
EU Method B.1 (Acute Toxicity (Oral))
Version / remarks:
1979
Deviations:
no
GLP compliance:
yes (incl. certificate)
Test type:
standard acute method
Limit test:
yes
Test material information:
Composition 1
Specific details on test material used for the study:
SOURCE OF TEST MATERIAL
- Source and lot/batch No.of test material: T 16/91
- Expiration date of the lot/batch: July 1992
- Purity test date:1992-05-13

STABILITY AND STORAGE CONDITIONS OF TEST MATERIAL
- Storage condition of test material: in the dark at room temperature
- Stability under test conditions: stable


Species:
rat
Strain:
Wistar
Sex:
male/female
Details on test animals and environmental conditions:
TEST ANIMALS
- Source: HOECHST AG, Kastengrund
- Weight at study initiation: 176 - 184 g (males); 178-208 g (females)
- Age at study initiation: males appr: 7 weeks, females appr. 8 weeks
- Fasting period before study: 16 hours before application
- Housing: in groups of 5 in macrolon cages
- Diet: ad libitum (Altromin 1324)
- Water: ad libitum (tap water)
- Acclimation period: at least 5 days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 22 +/- 3
- Humidity (%): 55 +/- 20
- Photoperiod (hrs dark / hrs light): 12/12
Route of administration:
oral: gavage
Vehicle:
water
Details on oral exposure:
VEHICLE
- Concentration in vehicle: 20 % (w/v)

MAXIMUM DOSE VOLUME APPLIED: 10 mL/kg bw

DOSAGE PREPARATION: The test item was diluted in water to a concentration of 20 % (w/v).
Doses:
2000 mg/kg bw
No. of animals per sex per dose:
5
Control animals:
no
Details on study design:
- Duration of observation period following administration: 14 days
- Frequency of observations and weighing: weekly
- Necropsy of survivors performed: yes
- Other examinations performed: clinical signs, body weight, macroscopically examinations
Statistics:
- Probit analysis according to Lindner and Weber
- method according to Fieller or Sidak
Preliminary study:
No details on preliminary study.
Key result
Sex:
male
Dose descriptor:
LD50
Effect level:
> 2 000 mg/kg bw
Based on:
test mat.
Key result
Sex:
female
Dose descriptor:
LD50
Effect level:
> 2 000 mg/kg bw
Based on:
test mat.
Mortality:
no mortality
Clinical signs:
Clinical signs were observed in male and female rats. On day of application reduced spontaneous reaction, drafted flanks, tumbling gait, pilorection, respiratory sounds were noticed. All clinical signs were reversible within 4 days.
Body weight:
No changes were observed.
Gross pathology:
No macroscopically visible changes were found.
Interpretation of results:
GHS criteria not met
Conclusions:
The LD50 value of the test item was determined to be > 2000 mg/kg bw.
Executive summary:

The acute oral toxicity of the test item was investigated in a study according to OECD TG 401 and EU Method B.1 with Wistar rats. Five animals of each sex were exposed to the test item by oral gavage at a limit dose of 2000 mg/kg bw. The animals were observed for 14 days. No mortality occured and the observed clinical signs (reduced spontaneous reaction, drafted flanks, tumbling gait, pilorection, respiratory sounds) were reversible within 4 days. The body weight was not affected. No macroscopic changes were noticed at necropsy. Therefore, the LD 50 was determined to be >2000 mg/kg bw.

Endpoint:
acute toxicity: oral
Type of information:
experimental study
Adequacy of study:
weight of evidence
Study period:
1984-09-03 to 1984-09-27
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
guideline study
Reference:
Composition 0
Qualifier:
according to
Guideline:
OECD Guideline 401 (Acute Oral Toxicity)
Version / remarks:
1981
Deviations:
no
Qualifier:
according to
Guideline:
EU Method B.1 (Acute Toxicity (Oral))
Version / remarks:
1979
Deviations:
no
GLP compliance:
yes (incl. certificate)
Test type:
standard acute method
Limit test:
no
Test material information:
Composition 1
Specific details on test material used for the study:
SOURCE OF TEST MATERIAL
- Batch No.of test material: VPS II-ROH T3
- Purity test date: 1984-04-03

STABILITY AND STORAGE CONDITIONS OF TEST MATERIAL
- Storage condition of test material: in the dark at 22°C


Species:
rat
Strain:
Wistar
Sex:
male/female
Details on test animals and environmental conditions:
TEST ANIMALS
- Source: HOECHST AG, Kastengrund
- Weight at study initiation: 166 - 210 g (males); 160-194 g (females)
- Fasting period before study: 16 hours before application
- Housing: in groups of 5 in macrolon cages (Type 4)
- Diet: ad libitum (Altromin 1324)
- Water: ad libitum (tap water)
- Acclimation period: at least 5 days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 22 +/- 2
- Humidity (%): 55 +/- 10
- Photoperiod (hrs dark / hrs light): 12/12
Route of administration:
oral: gavage
Vehicle:
water
Details on oral exposure:
VEHICLE
- Concentration in vehicle: 25 % (w/v)

MAXIMUM DOSE VOLUME APPLIED: 16 mL/kg bw

DOSAGE PREPARATION: The test item was diluted in water to a concentration of 25 % (w/v).
Doses:
1250, 2000, 2500, 2800, 3150 and 4000 mg/kg bw
No. of animals per sex per dose:
5 (except 1250, 4000 mg/kg bw: only females, 2800 mg/kg bw: only males)
Control animals:
no
Details on study design:
- Duration of observation period following administration: 14 days
- Frequency of observations and weighing: weekly
- Necropsy of survivors performed: yes
- Other examinations performed: clinical signs, body weight, macroscopically examinations
Statistics:
- Probit analysis according to Lindner and Weber
- method according to Fieller or Sidak
Preliminary study:
No details on preliminary study.
Key result
Sex:
male
Dose descriptor:
LD50
Effect level:
ca. 3 000 mg/kg bw
Based on:
test mat.
Key result
Sex:
female
Dose descriptor:
LD50
Effect level:
2 980 mg/kg bw
Based on:
test mat.
Mortality:
males: at 3150 mg/kg bw: 4/5
females: at 2500 mg/kg bw: 2/5, at 3150 mg/kg bw: 3/5, at 4000 mg/kg bw: 4/5
Clinical signs:
Clinical signs were observed in male and female rats. On day of application reduced spontaneous reaction, drafted flanks, tumbling gait, squatting position, pallor, piloerection, narrowed palpebral fissure and respiratory sounds were noticed. All clinical signs were reversible within 2 days in the surviving animals. One male in the 3150 mg/kg bw group showed reduced spontaneous reaction, drafted flanks, pallor, piloerection and squatting position until death on day 6.
Body weight:
No changes were observed.
Gross pathology:
Examination of the animals having died until day 2 (male and female):
- bleedings in the stomach wall, stomach filled with brownish liquid, yellow to yellow-brown gelatinous mass in small intestine, mucous membrane of the small intestine reddened
- peritoneum and pancreas reddened, adrenal glands dark coloured, vessels injected, liver partly discoloured (grey-brown spots)
- lungs partly discoloured (green-brown / grey)

Examination of the animals having died at day 5/6 (male):
- adhesion of liver with stomach, pancreas, small intestine and spleen, stomach wall perforated, stomach contents displaced (in abdomen area)

No macroscopic visible changes were found in the surviving animals.
Interpretation of results:
GHS criteria not met
Conclusions:
The LD50 value of the test item was determined to be ca. 3000 mg/kg bw for males and 2980 mg/kg bw for females.
Executive summary:

The acute oral toxicity of the test item was investigated in a study according to OECD TG 401 and EU Method B.1 with Wistar rats. Five animals of each sex were exposed to the test item by oral gavage at concentrations of 1250, 2000, 2500, 2800, 3150 and 4000 mg/kg bw. The animals were observed for 14 days. Mortality started occuring at 3150 mg/kg bw for males and 2500 mg/kg bw for females. The observed clinical signs (reduced spontaneous reaction, drafted flanks, tumbling gait, squatting position, pallor, piloerection, narrowed palpebral fissure, respiratory sounds) were reversible within 2 days, except for one male witch died on day 5/6. The body weight was not affected. Macroscopic changes noticed at necropsy were concerning liver, stomach, pancreas, small intestine and peritoneum. Therefore, the LD 50 was determined to be ca. 3000 mg/kg bw for males and 2980 mg/kg bw for females.

Endpoint conclusion
Endpoint conclusion:
adverse effect observed
Dose descriptor:
LD50
2 980 mg/kg bw
Quality of whole database:
Guideline and GLP study

Acute toxicity: via inhalation route

Endpoint conclusion
Endpoint conclusion:
no study available

Acute toxicity: via dermal route

Endpoint conclusion
Endpoint conclusion:
no study available

Additional information

Two studies are available for assessing the acute oral toxicity of the test item:

The acute oral toxicity of the test item was investigated in a study according to OECD TG 401 and EU Method B.1 with Wistar rats. Five animals of each sex were exposed to the test item by oral gavage at a limit dose of 2000 mg/kg bw. The animals were observed for 14 days. No mortality occured and the observed clinical signs (reduced spontaneous reaction, drafted flanks, tumbling gait, pilorection, respiratory sounds) were reversible within 4 days. The body weight was not affected. No macroscopic changes were noticed at necropsy. Therefore, the LD 50 was determined to be >2000 mg/kg bw.

The acute oral toxicity of the test item was further investigated in another study according to OECD TG 401 and EU Method B.1 in Wistar rats. Five animals of each sex were exposed to the test item by oral gavage at concentrations of 1250, 2000, 2500, 2800, 3150 and 4000 mg/kg bw. The animals were observed for 14 days. Mortality started occuring at 3150 mg/kg bw for males and 2500 mg/kg bw for females. The observed clinical signs (reduced spontaneous reaction, drafted flanks, tumbling gait, squatting position, pallor, piloerection, narrowed palpebral fissure, respiratory sounds) were reversible within 2 days, except for one male witch died on day 5/6. The body weight was not affected. Macroscopic changes noticed at necropsy were concerning liver, stomach, pancreas, small intestine and peritoneum. Therefore, the LD 50 was determined to be ca. 3000 mg/kg bw for males and 2980 mg/kg bw for females.

As a conclusion, the LD50 value was found to be > 2000 mg/kg bw in Wistar rats.

Justification for classification or non-classification

Classification, Labelling, and Packaging Regulation (EC) No 1272/2008

The available experimental test data are reliable and suitable for classification purposes under Regulation (EC) 1272/2008 (CLP). As a result the substance is not considered to be classified for acute toxicity under Regulation (EC) No 1272/2008 as amended for the tenth time in Regulation(EU) No 2017/776.