Registration Dossier

Administrative data

Endpoint:
acute toxicity: oral
Type of information:
experimental study
Adequacy of study:
key study
Study period:
1990-10-19 to 1991-03-13
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
other: Guideline-conform study under GLP without deviations.

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
1991
Report Date:
1991

Materials and methods

Test guidelineopen allclose all
Qualifier:
according to
Guideline:
OECD Guideline 401 (Acute Oral Toxicity)
Deviations:
no
Qualifier:
according to
Guideline:
EU Method B.1 (Acute Toxicity (Oral))
Deviations:
no
GLP compliance:
yes
Test type:
standard acute method
Limit test:
no

Test material

Reference
Name:
Unnamed
Type:
Constituent

Test animals

Species:
rat
Strain:
Wistar
Sex:
male/female

Administration / exposure

Route of administration:
oral: gavage
Vehicle:
water
Remarks:
Distilled water
Details on oral exposure:
VEHICLE
- Concentration in vehicle: 56 - 180 mg/l
- Amount of vehicle (if gavage): 10 ml/kg bw
- Justification for choice of vehicle: no justification given
- Lot/batch no. (if required): not applicable
- Purity: chemical analysis of water given in the original study report

MAXIMUM DOSE VOLUME APPLIED: 1800 mg/kg body weight. (per 10 ml vehicle / kg bw)

DOSAGE PREPARATION (if unusual): not applicable

CLASS METHOD (if applicable)
not applicable
Doses:
560, 1000, and 1800 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: Days 1 (pre-administration), 8 and 15 and at death (if found dead after day 1).
- Necropsy of survivors performed: yes
- Other examinations performed: clinical signs, body weight
Statistics:
The LD50 values and the associated 95% confidence interval, the slope of the dose mortal i t y curve were calculated using the Maximum lilkelihood method (Finney, D.J. Probit Analyses, 3rd Edn., Cambridge University Press, 1971).

Results and discussion

Effect levelsopen allclose all
Sex:
male/female
Dose descriptor:
LD50
Effect level:
1 406 mg/kg bw
Based on:
test mat.
95% CL:
1 012 - 3 186
Remarks on result:
other: Slope of the mortality curve: 3.7
Sex:
male
Dose descriptor:
LD50
Effect level:
1 571 mg/kg bw
Based on:
test mat.
95% CL:
1 130 - 3 909
Sex:
female
Dose descriptor:
LD50
Effect level:
ca. 1 228 mg/kg bw
Based on:
test mat.
Remarks on result:
other: Estimated value, calculations invalid according to Finney.
Clinical signs:
Signs of systemic toxicity observed during the study period in each dose group were as follows:
1800 mg/kg body weight: lethargy, piloerection, hunched posture, absence of reaction to external stimuli, dark appearance of the eyes - ears - tail
1000 mg/kg body weight: lethargy, piloerection, ataxia, dark appearance of the eyes - ears - tail - legs
560 mg/kg body weight: dark appearance of the eyes, ears, tail and legs
All changes in clinical appearance had disappeared by the second week of observation.
Body weight:
Animals found dead from day 2 onwards showed body weight loss on the day of death.
With the exception of 1 male treated at 1800 mglkg body weight, which showed slight body weight gain over the first week of observation, body weight gain shown by surviving animals over the study period was considered to be similar to that expected of normal untreated animals of the same age and strain.
Gross pathology:
Macroscopic post mortem examination of the animals that died during the study revealed the following abnormalities in each group:
1800 mg/kg body weight: bluelgreen organs, blue stomach contents
1000 mg/kg body weight: bluelgreen organs, blue stomach contents
560 mg/kg body weight: haemorrhages in the glandular stomach

Macroscopic post mortem examination of the surviving animals at termination did not reveal any abnormalities that were not commonly noted among rats of this age and strain. One male of the 1800 mg/kg group and 1 male of the 1000 mg/kg group were partially cannibalised.
Other findings:
- Organ weights: not recorded
- Histopathology: not conducted
- Potential target organs: not specified
- Other observations:

Any other information on results incl. tables

Tab. 1: The following mortality rates were observed:

  Dose level mg/kg bw  Males  Females  Sexes combined 
  1800  3 / 5 4 / 5  7 / 10 
  1000  1 / 5  1 / 5   2 / 10
   560 0 / 5  1 / 5   1 / 10

Applicant's summary and conclusion

Interpretation of results:
Category 4 based on GHS criteria
Remarks:
Migrated information
Conclusions:
The oral LD50 value of the substancein rats was 1406 mg/kg body weight for the sexes combined and 1571 mg/kg body weight for males alone. The estimated value for females alone was 1228 mg/kg body weight. According to the new CLP regulation (EU version of the UN GHS), the substance should be classified as acute oral. tox. category 4.