Registration Dossier

Administrative data

Endpoint:
acute toxicity: oral
Type of information:
experimental study
Adequacy of study:
key study
Study period:
from January to February 1996
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
other: guideline study

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
1996
Report Date:
1996

Materials and methods

Test guideline
Qualifier:
according to
Guideline:
OECD Guideline 423 (Acute Oral toxicity - Acute Toxic Class Method)
Deviations:
yes
Remarks:
- According to Annex 3c the lower dose (200 mg) should be applied first to the same sex that was treated with 2000 mg/kg
GLP compliance:
no
Test type:
acute toxic class method
Limit test:
no

Test material

Reference
Name:
Unnamed
Type:
Constituent

Test animals

Species:
rat
Strain:
other: HAN: WIST (SPF)
Sex:
male/female
Details on test animals and environmental conditions:
TEST ANIMALS
- Source: Schering AG, Germany
- Mean weight at study initiation: 105-113 g (males) or 89-91 g (females)
- Housing: 1 animal per cage
- Diet: ad libitum
- Water: ad libitum
- Acclimation period: at least 7 days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 21 - 23
- rel. Humidity (%): 50 - 58
- Photoperiod (hrs dark / hrs light): 12 / 12

Administration / exposure

Route of administration:
oral: gavage
Vehicle:
other: 900 mg NaCl + 85 mg Myrj 53 ad 100 ml bidist. water
Doses:
2000 and 200 mg/kg bw
No. of animals per sex per dose:
3
Control animals:
no

Results and discussion

Effect levels
Sex:
male/female
Dose descriptor:
LD50
Effect level:
> 300 - < 500 mg/kg bw
Based on:
test mat.
Mortality:
After 2000 mg/kg bw all animals died within 3 hours on day 1 of the test. No mortality was observed after adiministration of 200 mg/kg bw in both sexes.
Clinical signs:
The main clinical findings after administration of 2000 mg/kg were apathy, prone position, unconsciousness, disturbances in gait, total and spontaneous twitches and a bluish discolouration of all hairless parts of the body prior to death. All animals treated with 200 mg/kg were without clinical findings over the whole study period.
Body weight:
The body weight gain was within the normal range for rats of the age and strain.
Gross pathology:
Autopsy revealed reddening of the glandular mucosa of the stomach in only one animal which died after application of 2000 mg/kg and no compound-related or suspected compound-related findings in the two other animals which died or in the animals which were sacrificed at the end of the study.

Applicant's summary and conclusion

Conclusions:
The acute oral toxicity of the test item was moderate with an LD50 value of > 300 < 500 mg/kg bw in rats according to ANNEX 3c of OECD TG 423 (1996). All males died after oral ingestion of 2000 mg/kg bw. All males and females dosed with 200 mg/kg bw survived. Clinical findings were limited to the 2000 mg/kg bw dose group. Body weight development was not affected. During autopsy reddening of the glandular mucosa of the stomach was described in only one animal which died after application of 2000 mg/kg
Executive summary:

The acute oral toxicity of the test item was moderate with an LD50 value of > 300 < 500 mg/kg bw in rats according to ANNEX 3c of OECD TG 423 (1996). All males died after oral ingestion of 2000 mg/kg bw. All males and females dosed with 200 mg/kg bw survived. Clinical findings were limited to the 2000 mg/kg bw dose group. Body weight development was not affected in all treated animals. During autopsy reddening of the glandular mucosa of the stomach was described in only one animal which died after application of 2000 mg/kg bw.