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Administrative data

Endpoint:
acute toxicity: oral
Type of information:
experimental study
Adequacy of study:
key study
Study period:
04 May - 31 Jul 2001
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
other: GLP - Guideline study

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
2001
Report date:
2001

Materials and methods

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

Test material

Constituent 1
Details on test material:
- Name of test material (as cited in study report): Y-15099
- Physical state: pale yellowish liquid
- Analytical purity: 99.6%
- Lot/batch No.: 18161-74
- Expiration date of the lot/batch: 2002-10-23
- Stability under test conditions: no data
- Storage condition of test material: room temperature

Test animals

Species:
rat
Strain:
Wistar
Sex:
male/female
Details on test animals or test system and environmental conditions:
TEST ANIMALS
- Source: RCC Ltd, Biotechnology and Animal Breeding Division, Füllinsdorf, Switzerland
- Age at study initiation: Males: 8 weeks, Females: 10 weeks
- Weight at study initiation: no data
- Fasting period before study: 16 - 20 hours
- Housing: In groups of 3 per sex in Makrolon type-4 cages with wire mesh tops and standardized softwood bedding (´Lignocel´ Schill AG, CH-4132 Muttenz/Switzerland).
- Diet: Pelleted standard Provimi Kliba 3422 rat maintenance diet, batch no. 07/00 (Provimi Kliba AG, CH-4303 Kaiseraugst/Switzerland) ad libitum. Results of analyses for contaminants are archived at RCC Ltd., Itingen.
- Water: Community tap-water, from Itingen ad libitum. Results of bacteriological, chemical and contaminant analyses are archived at RCC Ltd, Itingen.
- Acclimation period: Under laboratory conditions, after health examinations. Only animals without any visible signs of illness were used for the study.

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 22 ± 3 °C
- Humidity (%): 30 - 70%
- Air changes (per hr): 10 - 15 air changes/hour
- Photoperiod (hrs dark / hrs light): 12 hours fluorescent light / 12 hours dark (light period between 6.00 and 18.00), music during the light period.

Administration / exposure

Route of administration:
oral: gavage
Vehicle:
unchanged (no vehicle)
Details on oral exposure:
MAXIMUM DOSE VOLUME APPLIED: 2 mL/kg bw

Doses:
2000 mg/kg bw
No. of animals per sex per dose:
3
Control animals:
no
Details on study design:
- Duration of observation period following administration: 14 days
- Frequency of observations and weighing: daily during acclimatization and at least once daily during days 1 - 15. Bodyweights on days 1 (pre-administration), 8 and 15. Clinical signs daily during acclimatization and at least four times (target times: approximately one, two, three and five hours) on test day 1 after the administration, depending on the occurrence of clinical signs of toxicity. At least once daily during days 2 - 15, depending on the occurrence of clinical signs of toxicity.
- Necropsy of survivors performed: yes
- Other examinations performed: clinical signs, body weight
Statistics:
No.

Results and discussion

Effect levels
Sex:
male/female
Dose descriptor:
LD50
Effect level:
> 2 000 mg/kg bw
Based on:
test mat.
Mortality:
No mortalities occured during the study.
Clinical signs:
No clinical signs of toxicity were noted.
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.

Applicant's summary and conclusion

Interpretation of results:
not classified
Remarks:
Migrated information Criteria used for interpretation of results: EU
Conclusions:
The median lethal dose of Y-15099 after single oral administration to rats of both sexes, observed over a period of 14 days is greater than 2000 mg/kg body weight.
Executive summary:

In an acute oral toxicity GLP study according to OECD 423, one group of three male and three female HanBrl: WIST (SPF) rats was treated by oral gavage with Y-15099 at 2000 mg/kg body weight. The test item was applied undiluted in volume of 2 mL/kg bw. The animals were examined for clinical signs daily during the acclimatization period, four times during test day 1 and once daily during test days 2 – 15. Mortality and viability were recorded daily during the acclimatization period and together with clinical signs at the same time intervals on test day 1 and at least once daily on test days 2 – 15. Body weights were recorded on day 1 (prior to administration) and on days 8 and 15. On day 15 all animals were necropsied and examined macroscopically. All animals survived until the end of the study period. No clinical signs were evident during the course of the study. The body weight of the animals was within the range commonly recorded for this strain and age. No macroscopic findings were observed at necropsy.

The median lethal dose of Y-15099 after single oral administration to rats of both sexes, observed over a period of 14 days is greater than 2000 mg/kg body weight.