Registration Dossier

Administrative data

Endpoint:
acute toxicity: oral
Type of information:
experimental study
Adequacy of study:
key study
Study period:
27 January 1997 to 18 April 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 guideline
Qualifier:
according to
Guideline:
OECD Guideline 401 (Acute Oral Toxicity)
Deviations:
no
GLP compliance:
yes
Test type:
acute toxic class method
Limit test:
yes

Test material

Reference
Name:
Unnamed
Test material form:
liquid
Details on test material:
Appearance: Amber liquid
Storage: Room temperature

Test animals

Species:
rat
Strain:
other: Crl:CDBR
Sex:
male/female
Details on test animals and environmental conditions:
TEST ANIMALS
- Females nulliparous and non-pregnant: Yes
- Age at study initiation: Males were approximately 8-9 weeks old and females were approximately 9-10 weeks old.
- Weight at study initiation: Males weighed 226 to 243 g and females weighed 181 to 204 g at initiation of dosing.
- Fasting period before study: After recording animal body weights, all food was removed from the animal cages at approximately 4:00 p.m. during the evening immediately prior to the day of administration of the test material. Food was withheld until completion of dosing the following morning.
- Housing: Single housed during the study period in suspended stainless steel and wire mesh with absorbent paper below cages.
- Diet: Ad libitum.
- Water: Automatic Watering System, ad libitum from municipal water source at the testing laboratory. Three were no known contaminants in the water believed to have been present at levels that may have interfered with the study.The availability of water was checked at least once daily for all animals.
- Acclimation period: 9 days; animals were examined for viability at least once daily.

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 64 to 72 degrees Fahrenheit (17.8 - 22.2 °C)
- Humidity (%): 30 to 70 percent relative humidity
- Photoperiod (hrs dark / hrs light): Approximately 12 hours light (0700 to 1900 hours) and 12 hours dark (1900 to 0700 hours) by automatic timer.

IN-LIFE DATES: From: To: 13 February 1997 to 27 February 1997

Administration / exposure

Route of administration:
oral: gavage
Vehicle:
unchanged (no vehicle)
Details on oral exposure:
MAXIMUM DOSE VOLUME APPLIED: 2000 mg/kg. The dose volume (2.13 mL/kg) was calculated by dividing the dose level (2000 mg/kg) by the density (0.94 g/ml). The dose volume was then multiplied by the body weight to arrive at the calculated dose.

DOSAGE PREPARATION: The test material was administered as received as a single oral intubation via syringe and a stainless steel, straight, ball tipped feeding needle.

Doses:
2000 mg/kg
No. of animals per sex per dose:
5 animals per sex per dose
Control animals:
no
Details on study design:
- Duration of observation period following administration: 14 days
- Frequency of observations and weighing: The animals were examined for viability twice daily Monday through Friday, and once daily on weekends and holidays (if applicable). Clinical observations were made as to the nature, onset, severity, and duration of toxicological signs at 1, 2, 4, and 6 hours after dosing, and once per day thereafter for a total of 14 days.
Body weights were recorded on the day prior to dosing (pretest), the day of dosing (Day 0), on Day 7, and on Day 14.
- Necropsy of survivors performed: Yes. After the Day 14 observations, all surviving animals were sacrificed by exsanguination following CO2 asphyxiation. A gross necropsy which included an examination of the external surface of the body, all orifices, the cranial, thoracic, and abdominal cavities and their contents was performed on all animals. No tissues were taken or preserved.
Statistics:
Statistical analyses included means and standard deviations of body weight and body weight change by group and sex.

Results and discussion

Effect levels
Key result
Sex:
male/female
Dose descriptor:
LD50
Effect level:
> 2 000 mL/kg bw
Based on:
test mat.
Mortality:
All animals survived to scheduled study termination on Day 14.
Clinical signs:
All animals were free of clinical signs of toxicity throughout the study.
Body weight:
All animals displayed increases in body weight over their initial values.
Gross pathology:
All animals were free of gross postmortem abnormalities.

Applicant's summary and conclusion

Interpretation of results:
GHS criteria not met
Conclusions:
Under the conditions of the study, the LD50 of the test material in male and female CrI:CDBR rats was estimated to be greater than 2000 mg/kg bodyweight and as such requires no classification in accordance with EU criteria.
Executive summary:

The acute oral toxicity of the test material was assessed in CrI:CDBR rats in accordance with the standardised guidelines OECD 401 and in compliance with GLP.

The test material was evaluated when administered as a single dose via oral intubation at a dose level of 2000 mg/kg to 5 male and 5 female rats. Clinical observations were made 1, 2, 4, and 6 hours after dose administration and once daily for 14 days. Body weights were recorded for all animals the day prior to dosing, the day of dosing (Day 0), Day 7, and Day 14. On Day 14, surviving animals were sacrificed and gross necropsies were performed.

All animals survived to scheduled termination on Day 14, were free of abnormalities throughout the study, and displayed increases in body weight over their initial values. At postmortem examination, all animals were free of gross abnormalities.

Oral intubation of the test material at a dose level of 2000 mg/kg did not produce any test material-related mortality or overt signs of toxicity under conditions of this study. Under the conditions of the study, the LD50 of the test material in male and female CrI:CDBR rats was estimated to be greater than 2000 mg/kg bodyweight and as such requires no classification in accordance with EU criteria.