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
Study period:
31 January 1990 - 5 March 1991
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
comparable to guideline study

Data source

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

Materials and methods

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

Test material

Reference
Name:
Unnamed
Type:
Constituent
Test material form:
liquid
Specific details on test material used for the study:
- Name of test material (as cited in study report): 6398-24-1, Project #90-018
- Physical state: clear colorless liquid
- Analytical purity: responsibility of the Sponsor
- Stability under test conditions: no apparent change in the physical state of the test article during administration
- Other: specific gravity= 0.8725 g/ml

Test animals

Species:
rat
Strain:
Sprague-Dawley
Sex:
male/female
Details on test animals and environmental conditions:
TEST ANIMALS
- Source: Charles River Laboratories, Inc., Wilmington, Massachusetts
- Age at study initiation: young adults
- Mean weight at study initiation:
500 mg/kg dose group: males: 184.2 g, females: 175.0 g
800 mg/kg dose group: males: 266.6 g, females: 203.6 g
1250 mg/kg dose group: males: 260.6 g, females: 209.6 g
2000 mg/kg dose group: males: 254.6 g, females: 199.6 g
- Housing: individually in stainless steel 1/2" wire mesh cages, sized in accordance with the "Guide for the Care and Use of Laboratory Animals" of
the Institute of Laboratory Animal Resources, National Research Council.
- Diet (e.g. ad libitum): Wayne Teklad Lab Blox, ad libitum
- Water (e.g. ad libitum): fresh tap water, ad libitum
- Acclimation period: minimum 5 days


ENVIRONMENTAL CONDITIONS
- Temperature (°C): 22°C±3°C
- Humidity (%): 30-70%
- Photoperiod (hrs dark / hrs light): 12h dark/12h light


Administration / exposure

Route of administration:
oral: gavage
Vehicle:
unchanged (no vehicle)
Details on oral exposure:
Not applicable
Doses:
Dose-range finding study: 500, 2500 and 5000 mg/kg
Definitive test: 500, 800, 1250 and 2000 mg/kg
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: Viability was checked daily. Clinical effects were observed for at 1, 4 and 24h after dosing and once daily thereafter. Body weights were recorded at study initiation, days 7 and 14 or when found dead.
- Necropsy of survivors performed: yes
Statistics:
LD50 calculations performed via Litchfield and Wilcoxon on Pharmacological Calculations System, version 4.1.

Results and discussion

Effect levelsopen allclose all
Key result
Sex:
male/female
Dose descriptor:
LD50
Effect level:
688.1 mg/kg bw
95% CL:
546.9 - 865.6
Sex:
male
Dose descriptor:
LD50
Effect level:
998.9 mg/kg bw
95% CL:
734 - 1 359.5
Sex:
female
Dose descriptor:
LD50
Effect level:
598.4 mg/kg bw
95% CL:
348.6 - 1 027.3
Mortality:
2/10 animals died at the 500 mg/kg dose;
6/10 animals died at the 800mg/kg dose;
10/10 animals died at both the 1250 and 2000 mg/kg dose levels.
Clinical signs:
Signs observed included decreased activity, piloerection, descreased muscle tone, abnormal gait, abnormal stance, diarrhea, chromodacryorrhea, dyspnea and prostration.
Body weight:
Final compared to initial body weight: body weight increase in both males and females at the 500 mg/kg dose level
Final compared to initial body weight: body weight increase in males at the 800 mg/kg dose level; decrease of body weight in females at 800 mg/kg dose level.
No final body weights reported for the 1250 mg/kg dose level.
Gross pathology:
Necropsy of the animals dying on study: distended and/or fluid-filled stomachs and intestines, pale livers and pale kidneys.
Terminal necropsy of the remaining animals: distended fluid-filled intestines in one female rat.

Any other information on results incl. tables

Results of dose range finding study:

Signs observed included decreased activity, abnormal stance, abnormal gait, and dyspnea. None of the animals died at the 500 mg/kg dose level. Two of two animals died at both the 2500 and 5000 mg/kg dose levels. Based upon these results, a definitive LD50 study was performed.

Applicant's summary and conclusion

Interpretation of results:
Category 4 based on GHS criteria
Conclusions:
The Acute Oral LD50 in male and female rats for the substance was determined to be 688.1 mg/kg (95%CL of 546.9 to 865.6 mg/kg). Based on the results of this study and according to the criteria of the CLP Regulation the substance should be classified as a category 4 acute oral toxicant.