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Administrative data

Endpoint:
acute toxicity: dermal
Type of information:
experimental study
Adequacy of study:
key study
Study period:
02 May - 06 Aug 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 402 (Acute Dermal Toxicity)
Deviations:
no
Qualifier:
according to guideline
Guideline:
EU Method B.3 (Acute Toxicity (Dermal))
Deviations:
no
GLP compliance:
yes
Test type:
standard acute 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 & Animal Breeding Devision, Füllinsdorf, Switzerland
- Age at study initiation: Males: 9 weeks; Females: 12 weeks
- Weight at study initiation: no data
- Housing: During acclimatization in groups of 5 per sex in Makrolon Type-4 cages with standard softwood bedding. Individually in Makrolon Type-3 cages with standard softwood bedding (´Lignocel´, Schill AG, CH-4132 Muttenz) during treatment and observation.
- Diet: Pelleted standard Kliba 3433, batch no. 07/00 rat maintenance diet (Provimi Kliba AG, CH-4303 Kaiseraugst) available ad libitum. Results of analyses for contaminants are archived at RCC Ltd, Itingen.
- Water: Community tap water from Itingen, available ad libitum. Results of bacteriological, chemical and contaminant analyses are archived at RCC Ltd, Itingen.

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

Type of coverage:
semiocclusive
Vehicle:
unchanged (no vehicle)
Details on dermal exposure:
TEST SITE
- Area of exposure: backs of the animals
- % coverage: 10% of the body surface
- Type of wrap if used: wrap was fixed with elastic adhesive bandage

REMOVAL OF TEST SUBSTANCE
- Washing (if done): yes, with lukewarm tap water
- Time after start of exposure: 24 hours after application

TEST MATERIAL
- Amount(s) applied (volume or weight with unit): 2 mL
- Constant volume or concentration used: yes


Duration of exposure:
24 hours
Doses:
2000 mg/kg bw
No. of animals per sex per dose:
5
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 one, two, three and approximately 5 hours after the test item administration, depending on the occurence of clinical signs of toxicity. At least once daily during days 2 - 15, depending on the occurence of clinical signs of toxicity. Bodyweights on days 1 (pre-administration), 8 and 15.
- 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 deaths occured during the study.
Clinical signs:
No clinical signs of toxicity were observed.
Body weight:
The body weight 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 dermal 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 dermal toxicity GLP study according to OECD 402, groups of five male and five female Hanlbm: WIST (SPF) rats were treated with Y-15099 at 2000 mg/kg bw by dermal application under semi-occlusive conditions (Damme, 2001). The test item was applied undiluted as delivered from the sponsor at a volume of 2 mL/kg bw. The animals were examined for clinical signs four times during the test day 1 and once daily during test days 2 – 15. Mortality/viability was recorded together with clinical signs at the same time intervals on test day 1. During test days 2 – 15 it was recorded two times a day. Body weights were recorded on day 1 prior to administration and on days 8 and 15. On day 15 all animals were euthanized and examined macroscopically. No deaths occurred during the study. No clinical signs of toxicity were observed during the observation period. 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 dermal administration to rats of both sexes, observed over a period of 14 days is greater than 2000 mg/kg body weight.