Registration Dossier

Administrative data

Endpoint:
acute toxicity: dermal
Type of information:
experimental study
Adequacy of study:
key study
Study period:
January 20 - February 15, 2011
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
other: Study performed according to current OECD test guidelines and GLP principles.

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
2011
Report Date:
2011

Materials and methods

Test guideline
Qualifier:
according to
Guideline:
OECD Guideline 402 (Acute Dermal Toxicity)
Deviations:
no
GLP compliance:
yes
Test type:
standard acute method
Limit test:
yes

Test material

Reference
Name:
Unnamed
Type:
Constituent
Details on test material:
- Name of test material (as cited in study report): E-Y110
- Physical state: Orange powder, solid
- Lot/batch No.: MB-1
- Expiration date of the lot/batch: Five years from shipment day (November 4, 2010)
- Storage condition of test material: Room temperature, in an air tight container in a dark place

Test animals

Species:
rat
Strain:
other: Crl:CD(SD)
Sex:
male/female
Details on test animals and environmental conditions:
TEST ANIMALS
- Source: Charles River Laboratories Japan, Inc. (Hino breeding center)
- Age at study initiation: 7 week old males and 10 week old females
- Weight at study initiation: 212.0 to 230.3 g for males and 219.6 to 241.6 g for females
- Fasting period before study: not applicable
- Housing: Stainless steel cages (WxDxH: 226x346x198mm), stainless steel cage racks and feeders, one animal per cage.
- Diet (ad libitum): Autoclave-sterilised pellet diet (CRF-1, Oriental Yeast Co., Ltd.). Each lot has been analysed: contaminants confirmed to be within acceptable limits established by the testing facility
- Water (ad libitum): Well water admixed with NaClO (about 2 ppm). Analysed twice a year: contaminants confirmed to be within acceptable limits established by the testing facility.
- Acclimation period: 6 days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 22.9-23.8
- Humidity (%): 48.4-57.0
- Air changes (per hr): 10 to 20
- Photoperiod (hrs dark / hrs light): 12/12

Administration / exposure

Type of coverage:
occlusive
Vehicle:
unchanged (no vehicle)
Remarks:
moistened with water (1 ml)
Details on dermal exposure:
TEST SITE
- Area of exposure: 4 x 5 cm
- % coverage: within 10% of total body surface
- Type of wrap: After hair clipping animals were fitted with a neck collar. The test substance was applied on a lint cloth lined with an impermeable sheet (Blenderm, 3M Health Care). This was covered with an elastic adhesive bandage (SILKYTEX white No.5, Alcare Co. Ltd.)

REMOVAL OF TEST SUBSTANCE
- Washing: wiped with a gauze sheet immersed in lukewarm water and water was removed with dry tissue paper. Animals remained fitted with neck collars during dosing and the recovery period.
- Time after start of exposure: 24 hours

TEST MATERIAL
- Amount(s) applied (volume or weight with unit): Required amount, calculated based on body weight on day of dosing. The lint cloth, where the substance was applied to, was moistened with an appropriate amount of water (1 ml).
Duration of exposure:
24 hours
Doses:
2000 mg/kg
No. of animals per sex per dose:
5
Control animals:
not required
Details on study design:
- Duration of observation period following administration: 14 days
- Frequency of observations and weighing: All animals were observed for their mortality and clinical signs before the dosing and at 30 min, 1, 3 and 6 hours postdose on the day of dosing (Day 1) and once daily for 14 days thereafter. All animals were subjected to body weight measurement before the dosing (Day 1) and on Days 4, 8 and 15.
- Necropsy of survivors performed: yes
- Other examinations performed: 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 death occured in either sex.
Clinical signs:
No substance related changes were seen.
Body weight:
No substance related changes were seen on body weight, although decreased body weight was seen in 1 male on Day 4, which was attributed to the occlusive application or fitted neck collar. Body weights of both sexes increased steadily on and after Day 8.
Gross pathology:
No abnormalities were seen in either sex.
Other findings:
No skin irritaion was observed.

Applicant's summary and conclusion

Interpretation of results:
not classified
Remarks:
Migrated information Criteria used for interpretation of results: EU
Conclusions:
The dermal LD50 of E-Y110 in rats was considered to be more than 2000 mg/kg bw under the conditions of this study (OECD 402).
Executive summary:

E-Y110 was administered once percutaneously to five male and five female Crl:CD(SD) rats at a dose of 2000 mg/kg bw to evaluate its acute dermal toxicity in accordance with OECD test guideline 402. The dose was applied for 24 hours occlusively after which the application site was wiped. As a result, no death occurred in either sex and no test substance related change was seen in clinical signs, body weight or necropsy. Therefore, the LD50 value of E-Y110 in rats was considered to be more than 2000 mg/kg bw under the conditions of this study.