Registration Dossier

Administrative data

Endpoint:
acute toxicity: oral
Type of information:
experimental study
Adequacy of study:
key study
Study period:
1997
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
guideline study

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
1997
Report Date:
1997

Materials and methods

Test guidelineopen allclose all
Qualifier:
according to
Guideline:
OECD Guideline 423 (Acute Oral toxicity - Acute Toxic Class Method)
Version / remarks:
of 22th March 1996
Deviations:
no
Qualifier:
equivalent or similar to
Guideline:
EU Method B.1 tris (Acute Oral Toxicity - Acute Toxic Class Method)
GLP compliance:
yes
Test type:
acute toxic class method
Limit test:
yes

Test material

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

Test animals

Species:
rat
Strain:
Wistar
Sex:
male/female
Details on test animals and environmental conditions:
TEST ANIMALS
- Source: Harlan Winkelmann, Borchen, Germany
- Age at study initiation: 8-10 weeks
- Weight at study initiation: 173 g (mean females) and 204 g (mean males)
- Housing: 3 animals per cage
- Diet (e.g. ad libitum): yes
- Water (e.g. ad libitum): yes
- Acclimation period: at least 5 days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 22 ± 2 °C
- Humidity (%): 55 ± 5 °C
- Air changes (per hr): 15 - 20 per hour
- Photoperiod (hrs dark / hrs light): 12 h rhythm

IN-LIFE DATES: From: To: 10 SEPT 1997 to 08 OKT 1997

Administration / exposure

Route of administration:
oral: gavage
Vehicle:
polyethylene glycol
Details on oral exposure:
application volume 10 mL/kg bw
The test substance was formulated in the application vehicle immediately prior to teatment. Therefore analytical investigations of the stability in the vehicle were not performed.
Doses:
2000 mg/kg bw as first dose in males; 200 mg/kg bw as second dose in male and females
No. of animals per sex per dose:
3 males and 6 females
Control animals:
no
Details on study design:
- Duration of observation period following administration: 14 days
- Frequency of observations: several times on the day of administration, and at least once daily during the following 14 day observation period
- body weights: weekly
- Necropsy of survivors performed: yes
Statistics:
not applicable

Results and discussion

Effect levels
Sex:
male/female
Dose descriptor:
LD50
Effect level:
> 200 mg/kg bw
Based on:
test mat.
Remarks on result:
other: LD50 between 200 and 2000 mg/kg bw
Mortality:
all 3 female rats died after administration of 2000 mg/kg bw within 1 hour
Clinical signs:
No clinical signs
Body weight:
no effects on weight gain of the surviving animals
Gross pathology:
Severe red discoloration of the stomach and small intestine was observed at necropsy in the intercurrent death animals (2000 mg/kg bw group). None of the sacrificed animals showed any noticable gross pathological findings (200 mg/kg bw group).

Any other information on results incl. tables

Dose (mg/kg bw) sex  toxicological result  mortality  onset of mortality
(1st) 2000 female 3 / 3 100 %  1h
(2nd) 200 female 3 / 0 ---   ---
 (2nd) 200 male  3 / 0  ---  ---

Toxicological results:

number of dead animals / number of animals treated

Applicant's summary and conclusion

Interpretation of results:
Category 4 based on GHS criteria
Executive summary:

The acute oral LD50 in rats was determined as > 200 mg/kg bw and < 2000 mg/kg bw based on the results of a limit dose study performed according to OECD TG 423. The test dose of 2000 mg/kg led to mortality of 3/3 females with severe red discoloration of the stomach and small intestine at necropsy. The second dose of 200 mg/kg bw tested in 3 male and 3 female rats was well tolerated without clinical signs or any noticeable gross pathological findings. Since the dose of 200 mg/kg bw turned out as the NOEL for both sexes it can be considered that the LD50 is > 300 mg/kg bw (Acute Tox 4), as shown in the flow chart in Annex 3c of OECD 423 (1996) and Annex 2d of OECD 423 (2001). The test substance should thus be regarded as harmful if swallowed.