Registration Dossier

Administrative data

Endpoint:
acute toxicity: dermal
Type of information:
experimental study
Adequacy of study:
key study
Study period:
2013-10-22 until 2013-11-05
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
other: GLP compliant, guideline study, no restrictions, fully adequate for assessment.

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
2014
Report Date:
2015

Materials and methods

Test guidelineopen allclose all
Qualifier:
according to
Guideline:
OECD Guideline 402 (Acute Dermal Toxicity)
Deviations:
no
Qualifier:
according to
Guideline:
EPA OPPTS 870.1200 (Acute Dermal Toxicity)
Deviations:
no
Qualifier:
according to
Guideline:
EU Method B.3 (Acute Toxicity (Dermal))
Deviations:
no
GLP compliance:
yes (incl. certificate)
Test type:
standard acute method
Limit test:
yes

Test material

Reference
Name:
Unnamed
Type:
Constituent
Test material form:
solid: crystalline
Details on test material:
- Physical state: Yellowish crystals
- Purity test date: 19 September 2013
- Expiration date of the lot/batch: End September 2015
- Stability under test conditions: Stable until end September 2015
- Storage condition of test material: Room temperature (<30°C), protected from light and humidity

Test animals

Species:
rat
Strain:
Wistar
Sex:
male/female
Details on test animals and environmental conditions:
TEST ANIMALS
- Source: Harlan Laboratories S.r.l., S.Pietro al Natisone (UD), Zona Industriale Azzida, 57, 33040, Italy.
- Strain: RccHan:WIST
- Age at study initiation: Young adult.
- Weight at study initiation: 214-243 g.
- Fasting period before study: None.
- Housing: Individually in Type II polypropylene/polycarbonate cages.
- Diet: ssniff® SM R/M "Autoclavable complete diet for rats and mice – breeding and maintenance" ad libitum. Ssniff Spezialdiäten GmbH, D-59494, Soest, Germany.
- Water: Municipal tap water ad libitum.
- Acclimation period: 6 Days.

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 22 ± 3
- Humidity (%): 30-70
- Air changes (per hr): 15-20
- Photoperiod (hrs dark / hrs light): 12/12

IN-LIFE DATES: From: 22 October 2013 To: 05 November 2013

Administration / exposure

Type of coverage:
semiocclusive
Vehicle:
unchanged (no vehicle)
Details on dermal exposure:
TEST SITE
- Area of exposure: Back (shaved approximately 24 hours before treatment)
- % coverage: Approximately 10%
- Type of wrap if used: Sterile gauze pads kept in contact with the skin by using a patch of adhesive hypoallergenic plaster. The entire trunk of the animal was then wrapped with semi occlusive plastic wrap.

REMOVAL OF TEST SUBSTANCE
- Washing (if done): Yes (body temperature water).
- Time after start of exposure: 24 hours

TEST MATERIAL
- Amount(s) applied (volume or weight with unit): 2000 mg/kg bw
- For solids, paste formed: Yes (appropriate amount of test item moistened with water and distributed as uniformly as possible onto the skin).

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: Observed on the day of treatment, at 1 and 5 hours after the application of the test item, and once each day for 14 days thereafter. Body weights recorded on Day 0 (before treatment) and on Days 7 and 14.
- Necropsy of survivors performed: Yes
Statistics:
Not applicable (limit test, no mortality).

Results and discussion

Effect levels
Sex:
male/female
Dose descriptor:
LD50
Effect level:
> 2 000 mg/kg bw
Based on:
test mat.
Mortality:
There were no mortalities.
Clinical signs:
There were no treatment related clinical signs or skin irritation.
Body weight:
There were no treatment related effects on body weight.
Gross pathology:
There were no treatment related macroscopic findings.

Applicant's summary and conclusion

Interpretation of results:
not classified
Remarks:
Migrated information Criteria used for interpretation of results: EU
Conclusions:
The acute median lethal dose (LD50) of the test item after single dermal administration was greater than 2000 mg/kg bw in male and female RccHan:WIST rats.
Executive summary:

A single administration of the test item at a dose of 2000 mg/kg body weight (bw) was applied dermally to 5 male and 5 female RccHan:WIST rats, followed by a 14-day observation period. The test item was applied as supplied. The application period was 24 hours. Clinical observations along with a check of viability and mortality 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. Rats were killed and subjected to a gross macroscopic examination at the end of the 2-week observation period (Day 14).

No mortality occurred during the 14-day observation period after a 24-hour dermal exposure test item to RccHan:WIST rats. No adverse clinical signs were observed after treatment with the test item or during the 14 day observation period. There were no treatment related effects on body weight or body weight gain during the observation period. There was no evidence of any treatment-related macroscopic findings at a dose level of of 2000 mg/kg bw at necropsy.

The acute median lethal dose (LD50) after a single dermal administration was greater than 2000 mg/kg bw in male and female RccHan:WIST rats.