Registration Dossier

Administrative data

Endpoint:
acute toxicity: oral
Type of information:
experimental study
Adequacy of study:
key study
Study period:
2000
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
other: Guideline study performed under GLP; minor deviations not considered to affect the integrity of the study.

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
2000
Report Date:
2000

Materials and methods

Test guidelineopen allclose all
Qualifier:
according to
Guideline:
OECD Guideline 423 (Acute Oral toxicity - Acute Toxic Class Method)
Deviations:
yes
Remarks:
The animals were not fasted overnight prior to dosing
Qualifier:
according to
Guideline:
EU Method B.1 tris (Acute Oral Toxicity - Acute Toxic Class Method)
Deviations:
yes
Remarks:
The animals were not fasted overnight prior to dosing
GLP compliance:
yes (incl. certificate)
Remarks:
inspected November 1998; signature: March 1999
Test type:
acute toxic class method
Limit test:
yes

Test material

Reference
Name:
Unnamed
Type:
Constituent
Test material form:
gas under pressure: refrigerated liquefied gas
Details on test material:
- Physical state: Colourless to pale yellow liquid
- Stability under test conditions: Stable under storage conditions; stability in vehicle unknown
- Storage condition of test material: In the original container, in the refrigerator (range of 4 ± 3 °C), away from direct sunlight.
- Other: safety precaution: Routine hygienic procedures were used to ensure the health and safety of the personnel.

Test animals

Species:
rat
Strain:
other: Hanlbm: WIST (SPF)
Sex:
male/female
Details on test animals and environmental conditions:
TEST ANIMALS
- Source: Recognised animal supplier
- Age at study initiation: 8-10 weeks
- Weight at study initiation: males 237 - 265.5g; females 186.2 - 195.5g
- Fasting period before study: fasted 1 hour before treatment.
- Housing: Groups of three per sex in Makrolon type-4 cages with standard softwood bedding.
- Diet (e.g. ad libitum): certified pelleted diet ad libitum
- Water (e.g. ad libitum): tap water ad libitum
- Acclimation period: one week

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 22 - 23.5
- Humidity (%): 40 - 61
- Air changes (per hr): 10 - 15
- Photoperiod: 12 hours light/12 hours dark

IN-LIFE DATES: 15/08/2000 To: 15/09/2000

Administration / exposure

Route of administration:
oral: gavage
Vehicle:
polyethylene glycol
Details on oral exposure:
VEHICLE
- Concentration in vehicle: 200mg/ml
- Amount of vehicle (if gavage): 10ml/kg
- Justification for choice of vehicle: not reported
- Lot/batch no. (if required): 40537 4/1 30600
- Purity: not reported

MAXIMUM DOSE VOLUME APPLIED: 10ml/kg

Doses:
2000 mg/kg
No. of animals per sex per dose:
3
Control animals:
no
Details on study design:
- Duration of observation period following administration: 15 days
- Frequency of observations and weighing: The animals were examined for clinical signs fourvtimes during test day 1 and once daily during test days 2-15. Mortality/viability was recordedvtogether with clinical signs at the same time intervals on test day 1 and then twice daily on test days 2-15. Body weights were recorded on day 1 prior to administration and on days 8 and 15.
- Necropsy of survivors performed: yes
- Other examinations performed: body weight.
Statistics:
No statistical analysis was used.

Results and discussion

Effect levels
Sex:
male/female
Dose descriptor:
LD50
Effect level:
> 2 000 mg/kg bw
Based on:
test mat.
Mortality:
No deaths occurred during the study.
Clinical signs:
Slight rales were noted in all female animals on test day 2. Somnolence was observed in all male animals from 2 to 5 hours after the administration and slightly ruffled fur was observed in the same males from 1 to 5 hours (2 males) or from 2 to 5 hours (1 male). Hunched posture was observed additionally in one male animal from 1 to 5 hours after the administration.
Body weight:
The body weight of the animals was within the range commonly recorded for this strain and age.
Gross pathology:
No macroscopic findings were observed at necropsy.

Applicant's summary and conclusion

Interpretation of results:
not classified
Remarks:
Migrated information Criteria used for interpretation of results: EU
Conclusions:
The acute oral median lethal dose (LD50) of the test material in male and female Hanlbm: WIST (SPF) strain of rat was greater than 2000 mg/kg body weight.
Executive summary:

The study was performed to EU Method B.1 and OECD 423 in accordance with GLP to assess the acute oral toxicity of the test material in the Hanlbm: WIST (SPF) strain of rat. The test material was administered orally, after fasting for 1 hour, once only by gavage. The test material concentration in the vehicle was 200 mg/ml and the administered volume of suspension was 10 ml/kg body weight. 3 male and 3 female test animals were dosed at 2000 mg/kg body weight. Clinical signs and bodyweight development were monitored during the study. All animals were subjected to gross necropsy after an observation period of 15 days. There were no deaths but slight rales were noted in all female animals on test day 2. Somnolence was observed in all male animals from 2 to 5 hours after the administration and slightly ruffled fur was observed in the same males from 1 to 5 hours (2 males) or from 2 to 5 hours (1 male). Hunched posture was observed additionally in one male animal (no.4) from 1 to 5 hours after the administration. Animals showed expected gains in bodyweight during the study. No test-related abnormalities were noted at necropsy. The acute oral median lethal dose (LD50) of the test material in the male and female Hanlbm: WIST (SPF) strain rat was greater than 2000 mg/kg bodyweight.