Registration Dossier

Administrative data

Endpoint:
acute toxicity: dermal
Type of information:
experimental study
Adequacy of study:
key study
Study period:
2014-10-08 to 2014-10-22
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
other: Guideline study

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
2015
Report Date:
2015

Materials and methods

Test guidelineopen allclose all
Qualifier:
according to
Guideline:
OECD Guideline 402 (Acute Dermal Toxicity)
Version / remarks:
1987
Deviations:
no
Qualifier:
according to
Guideline:
EPA OPPTS 870.1200 (Acute Dermal Toxicity)
Version / remarks:
1998
Deviations:
no
Qualifier:
according to
Guideline:
EU Method B.3 (Acute Toxicity (Dermal))
Version / remarks:
2008
GLP compliance:
yes
Test type:
fixed dose procedure
Limit test:
yes

Test material

Reference
Name:
Unnamed
Type:
Constituent
Test material form:
other: liquid
Details on test material:
Characteristics: Slightly yellowish liquid

Test animals

Species:
rat
Strain:
Wistar
Sex:
male/female
Details on test animals and environmental conditions:
- Strain: CRL:(WI) rats
- Source: Charles River Laboratories, Research Models and Services, Germany GmbH, Sandhofer Weg 7, D-97633 Sulzfeld
- Age: young adult rats
-Weight: between 213 - 240g
- Controls: no
- Diet: ad libitum, ssniff® SM R/M "complete diet for rats and mice" produced by ssniff Spezialdiäten GmbH, D-59494 Soest Germany
- Water: ad libitum, tab water
- Acclimation period: 6 days
- Housing: individual caging
ENVIRONMENTAL CONDITIONS
- Temperature (°C): 19.8 - 24.9°C
- Humidity (%): 49 - 63 %
- Photoperiod (hrs dark / hrs light): 12 hours daily, from 6.00 a.m. to 6.00 p.m.
- Ventilation: 15-20 air exchanges/hour

Administration / exposure

Type of coverage:
semiocclusive
Vehicle:
unchanged (no vehicle)
Details on dermal exposure:
- Method of administration:
The back of each animal was shaved (approximately 10 % area of the total body surface) approximately 24 hours prior to treatment.

The test item was applied as a single dose as supplied to the shaved skin and remained in contact with the skin for the 24-hour exposure period.
Sterile gauze pads were placed on the skin of rats to cover the test item. These gauze pads were kept in contact with the skin by a patch with adhesive hypoallergenic plaster. The entire trunk of the animal was then wrapped with semi occlusive plastic wrap for 24 hours

At the end of the exposure period, the area of skin treated with the test item was washed with water of body temperature.

The test patch was occlusive. The test item was held in contact with the skin with 8 layers of gauze. The gauze was covered with a plastic sheet and
secured with adhesive plaster strips on the application site for 24 hours.
Duration of exposure:
24 hours
Doses:
- 2000 mg/kg bw, the test item was administered as a single dose as supplied by the Sponsor without using any vehicle
No. of animals per sex per dose:
5
Control animals:
not required
Details on study design:
EXAMINATIONS: 
- Clinical signs:  on the day of treatment at 1 and 5 hours after application of the test item and once each day for 14 days thereafter. Observations
included the skin and fur, eyes and mucous membranes, the respiratory, circulatory, autonomic and central nervous system, somatomotor activity
and behaviour pattern. Particular attention was directed to observation of tremors, convulsions, salivation, diarrhoea, lethargy, sleep and coma.
- Skin irritation: daily
- Body weights: days 0, 7, and 14
- Post dose observation period: 14 days
- Macroscopic examination:  day  14 
Statistics:
not required

Results and discussion

Effect levels
Sex:
male/female
Dose descriptor:
LD50
Effect level:
> 2 000 mg/kg bw
Remarks on result:
other: no mortalities
Mortality:
Test item did not cause mortality at the dose level of 2000 mg/kg bw.
Clinical signs:
No dermal signs were observed after treatment with the test item during the 14-day observation period.
No clinical signs were observed after the treatment with the test item during the 14 day observation period
Body weight:
There were no effects on body weight in any animal during the study.
Gross pathology:
There was no evidence of the macroscopic observations at a dose level of 2000 mg/kg bw at necropsy.
Other findings:
No other findings

Any other information on results incl. tables

No further information

Applicant's summary and conclusion

Interpretation of results:
not classified
Remarks:
Migrated information Criteria used for interpretation of results: EU
Conclusions:
The acute dermal median lethal dose (LD50) of the test item was found to be greater than 2000 mg/kg body weight in
male and female CRL:(WI) rats.
Executive summary:

An acute dermal toxicity study was performed with the test item in CRL:(WI) rats, in compliance with OECD Guideline No.: 402.

A limit test was carried out at 2000 mg/kg body weight (bw) in both sexes (5 rats/sex). The test item was applied as supplied as a single dermal 24-hour exposure followed by a 14‑day observation period.

Clinical observations were performed on all animals at 1 and 5 hours after dosing and daily for 14 days thereafter.

Body weight was measured prior to dosing on Day 0 and on Days 7 and 14.

Gross macroscopic examination was performed on all animals at the end of the 2-week observation period (Day 14).

The results of the study were summarized as follows.

Mortality: Test item did not cause mortality at the dose level of 2000 mg/kg bw.

Systemic clinical signs : No clinical signs were observed after the treatment with the test item during the 14 day observation period.

Local dermal signs: No dermal signs were observed after treatment with the test item during the 14-day observation period.

Body weight: There were no effects on body weight in any animal during the study.

Necropsy: There was no evidence of the macroscopic observations at a dose level of 2000 mg/kg bw at necropsy.

Conclusions

The acute dermal median lethal dose (LD50) of the test item was found to be greater than 2000 mg/kg body weight in male and female CRL:(WI) rats.