Registration Dossier

Administrative data

Endpoint:
acute toxicity: oral
Type of information:
experimental study
Adequacy of study:
key study
Study period:
2007-02-21 to 2007-03-28
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
guideline study

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
2007
Report Date:
2007

Materials and methods

Test guidelineopen allclose all
Qualifier:
according to
Guideline:
OECD Guideline 423 (Acute Oral toxicity - Acute Toxic Class Method)
Deviations:
no
Qualifier:
according to
Guideline:
EU Method B.1 tris (Acute Oral Toxicity - Acute Toxic Class Method)
Deviations:
no
GLP compliance:
yes (incl. certificate)
Remarks:
: certificate issued by Swiss GLP Monitoring Authorities
Test type:
acute toxic class method
Limit test:
no

Test material

Reference
Name:
Unnamed
Type:
Constituent
Test material form:
liquid
Details on test material:
- Name of test material (as cited in study reports): T002675, TIC876
- Physical state: liquid
- Appearance: colorless to yellowish liquid
Specific details on test material used for the study:
SOURCE OF TEST MATERIAL
- Name of test material (as cited in study report): T002675 (TIC876)
- Physical state: liquid, colorless to yellowish
- Analytical purity: 97.76%
- Lot/batch No.: 603T-1
- Expiration date of the lot/batch: 2007-12-19

STABILITY AND STORAGE CONDITIONS OF TEST MATERIAL
- Storage condition of test material: at room temperature (range of 20 +/- 5 °C), light protected
- Stability under test conditions: unknown in PEG 300, is excluded from teh statement of compliance

TREATMENT OF TEST MATERIAL PRIOR TO TESTING
- Treatment of test material prior to testing: The dose formulations were made shortly before each dosing occasion using a magnetic stirrer as homogenizer. The test item was weighed into a tared glass beaker on a suitable precision balance and the vehicle added (weight:volume). Homogeneity of the test item in the vehicle was maintained during administration using a magnetic stirrer.

Test animals

Species:
rat
Strain:
other: HanRcc: Wist (SPF)
Sex:
female
Details on test animals and environmental conditions:
TEST ANIMALS
- Source: RCC Ltd., Laboratory Animal Services CH-4414 Füllinsdorf / Switzerland
- Age when treated: 11 weeks
- Weight at study initiation (day 1): 178.1-191.7 g
- Fasting period before study: approximately 18 to 19 hours, access to water was permitted. Food was provided again approximately 2 hours after dosing.
- Housing: in groups of three in Makrolon type-4 cages with wire mesh tops and standard softwood bedding
- Diet (e.g. ad libitum): pelleted standard Provimi Kliba 3433 rat/mouse maintenance diet, batch no. 89/06, ad libitum
- Water (e.g. ad libitum): community tap water from Füllinsdorf, ad libitum
- Acclimation period: 2007-02-21 to 2007-02-27 (females, 2000 mg/kg); 2007-02-23 to 2007-03-05 (females, 300 mg/kg); 2007-03-07 to 2007-03-13 (females, 300 mg/kg)

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 22 +/- 3 °C
- Humidity (%): 30 - 70
- Air changes (per hr): 10 - 15
- Photoperiod (hrs dark / hrs light): 12 / 12, music during light period

IN-LIFE DATES: From: 2007-02-28 To: 2007-03-03 (females, 2000 mg/kg); 2007-03-06 To: 2007-03-20 (females, 300 mg/kg); 2007-03-14 To: 2007-03-28 (females, 300 mg/kg)

Administration / exposure

Route of administration:
oral: gavage
Vehicle:
polyethylene glycol
Remarks:
PEG 300
Details on oral exposure:
VEHICLE
- Concentration in vehicle: 0.2 or 0.03 g/mL
- Amount of vehicle (if gavage): 10 mL/kg bw
- Justification for choice of vehicle: The vehicle was chosen after a non-GLP solubility trial which was performed before the study initiation date.
- Lot/batch no. (if required): 130022563006152

MAXIMUM DOSE VOLUME APPLIED:
- 10 mL/kg bw
Doses:
2000 mg/kg bw or 300 mg/kg bw
No. of animals per sex per dose:
3 females/ group,
2 groups at 300 mg/kg bw (6 total)
1 group at 2000 mg/kg bw (3 total)
Control animals:
no
Details on study design:
- Duration of observation period following administration: 14 days
- Frequency of observations: The animals were examined daily during the acclimatization period and mortality, viability and clinical signs were recorded; all animals were examined for clinical signs at approximately 30 minutes, 1, 2, 3 and 5 hours after treatment on day 1 and once daily during test days 2-15; mortality/viability was recorded at approximately 30 minutes, 1, 2, 3 and 5 hours after administration on test day 1 (with the clinical signs) and twice daily during 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: macroscopic examination
Statistics:
No statistical analysis was used.

Results and discussion

Effect levels
Key result
Sex:
female
Dose descriptor:
LD50
Effect level:
> 300 - < 2 000 mg/kg bw
Remarks on result:
other: no data on confidence level
Mortality:
All the animals treated with 2000 mg/kg died spontaneously 2 or 3 days after treatment. No deaths occurred in the animals treated with 300 mg/kg during the study.
Clinical signs:
The animals treated with 2000 mg/kg all showed a slight to moderate ruffled fur and a slight to moderate sedation from the 30-minute reading until their respective deaths. The animals also had closed eyes between 30 minutes after treatment and the 3-hour reading or their respective deaths. A poor coordination was noted at the 2- and 3-hour readings in the three animals. All of the animals had in addition a hunched posture from the 5 hours or 2 days after treatment, up to test day 3. One animal showed additionally soft feces and deep respiration 3 days after treatment.

The animals treated with 300 mg/kg all showed a slight to moderate ruffled fur, a slight to moderate sedation and a hunched posture. The symptoms were notable from the 30-minute or 1-hour reading to the 5-hour or 2-day reading, respectively.
Body weight:
The body weight of the animals was within the range commonly recorded for this strain and age.
Gross pathology:
One animal from the 2000 mg/kg treatment group which died spontaneously showed a distended stomach, and the jejunum and ileum were empty. No other macroscopic findings were recorded at necropsy.

Applicant's summary and conclusion

Interpretation of results:
Category 4 based on GHS criteria
Conclusions:
The LD50 of the test substance after single oral administration to female rats, observed over a period of 14 days was greater than 300 mg/kg bw and less than 2000 mg/kg bw.