Registration Dossier

Administrative data

Endpoint:
acute toxicity: oral
Type of information:
experimental study
Adequacy of study:
key study
Study period:
September / October 2000
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
guideline study

Data source

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

Materials and methods

Test guideline
Qualifier:
according to
Guideline:
OECD Guideline 423 (Acute Oral toxicity - Acute Toxic Class Method)
Version / remarks:
1996
Deviations:
no
GLP compliance:
yes
Test type:
acute toxic class method
Limit test:
yes

Test material

Reference
Name:
Unnamed
Type:
Constituent
Test material form:
solid: crystalline
Remarks:
wax

Test animals

Species:
rat
Strain:
Sprague-Dawley
Sex:
male/female
Details on test animals and environmental conditions:
TEST ANIMALS
- Source: Charles River UK
- Females nulliparous and non-pregnant: yes
- Age at study initiation: 206-240 g (females), 205-220 g (males)
- Weight at study initiation: 8 weeks
- Fasting period before study: yes
- Housing: by group of 3, by sex
- Diet (e.g. ad libitum): ad libitum
- Water (e.g. ad libitum):ad libitum
- Acclimation period: at least 5 days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 19-25
- Humidity (%): 30-70
- Air changes (per hr): at least 15
- Photoperiod (hrs dark / hrs light): 12/12

Administration / exposure

Route of administration:
oral: gavage
Vehicle:
arachis oil
Details on oral exposure:
The test mateiral was fresly prepared as a solution at the appropriate concentration in arachis oil BP. If necessary the test material was warmed to approximately 50°C to produce a liquid prior to formulation.
All animals were dosed once only by gavage, using a metal cannula attached to a graduated syringe. The volume administered to each animal was calculated according to the fasted bw at the time of dosing.
Dose volume : 10 ml/kg
Doses:
2000 mg/kg bw
No. of animals per sex per dose:
3 females and 4 males
Control animals:
no
Details on study design:
The animals were observed for deaths or overt signs of toxicity, 30 min, 1h, 2h and 4h after dosing and subsequently once daily for up to 14 days.
individual bodyweights were recorded prior to dosing and seven and fourteen days after treatment or at death.
At the end of the observation period the surviving animals were killed by cervical dislocation. All animal including the one that was killed in extremis were subjected to gross pathological examination. This consisted of an external examination and opening of the abdonimal and thoracic cavities for examination of major organs. The appearance of any macroscopic abnormalities was recorded. No tissues were retained.
Statistics:
no

Results and discussion

Effect levels
Key result
Sex:
male/female
Dose descriptor:
LD0
Effect level:
> 2 000 mg/kg bw
Based on:
test mat.
Remarks on result:
not determinable due to absence of adverse toxic effects
Mortality:
No treatment related deaths were noted.
One male animal was killed in extremis approximately 3 hours after dosing. necropsy confirmed the animal had been mal-dosed and an additional animal was treated.
Clinical signs:
Signs of systemic toxicity noted in males were hunched posture, decreased respiration and noisy respiration. Two males recovered four or five days after dosing. One male and all females appeared normal throughout the study.
The animal killed in extremis due to the mal-doseing showed signs of hunched posture, lethargy, noisy respiration and gasping respiration one and two hours after dosing.
Body weight:
Expected gains in bodyweight were noted over the study period.
Gross pathology:
Off white liquid present in the lungs (considered to be the test material) was noted at necropsy of the male that was killed in extremis during the day of dosing and confirmed mal-dosing.
No abnormalities were noted at necropsy of animals that were killed at the end of the study.
Other findings:
no

Applicant's summary and conclusion

Interpretation of results:
GHS criteria not met
Conclusions:
The oral acute median lethal dose (LD50) of the test mateiral in the SD rat was estimated greater than 2000 mg/kg bw.
Executive summary:

The study was performed to assess the acute oral toxicity of the tes material following a single oral administration in the SD strain rat (OECD 423).

A group of 3 fasted females was treated with 2000 mg/kg bw. This was followed by a group of 3 fasted males at the same dose level. An additional male animal was treated with 2000 mg/kg to replace a mal-dosed male animal. The test material was administered orally as a solution in arachis oil BP. Clinical signs and bodyweight development were monitored during the study. All animals were subjected to gross necropsy examination.

No treatment related deaths were noted. One male animal was killed in extremis approximately three hours after dosing. Necropsy confirmed the animal had been mal-dosed and an additional animal was treated. Signs of systemic toxicity noted in males were hunched posture, decreased respiration and noisy respiration. Two males receovered four or five days after dosing. One male and all females appeared normal throughout the study. Expected gains in bodyweight were noted over the study period. No abnormalities were noted at necropsy of animals that were killed at the end of the study.

The oral acute median lethal dose (LD50) of the test mateiral in the SD rat was estimated greater than 2000 mg/kg bw.