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Toxicological information

Skin irritation / corrosion

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Administrative data

Endpoint:
skin irritation: in vivo
Type of information:
experimental study
Adequacy of study:
key study
Study period:
2013
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
guideline study

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
2013
Report Date:
2013

Materials and methods

Test guidelineopen allclose all
Qualifier:
according to
Guideline:
OECD Guideline 404 (Acute Dermal Irritation / Corrosion)
Version / remarks:
2002
Qualifier:
according to
Guideline:
EPA OPPTS 870.2500 (Acute Dermal Irritation)
Version / remarks:
1998
Qualifier:
according to
Guideline:
other: JMAFF Guidelines including the most recent partial revisions
Version / remarks:
2011
Qualifier:
according to
Guideline:
EU Method B.4 (Acute Toxicity: Dermal Irritation / Corrosion)
Version / remarks:
2008
GLP compliance:
yes

Test material

Reference
Name:
Unnamed
Type:
Constituent
Specific details on test material used for the study:
SOURCE OF TEST MATERIAL
- Source and lot/batch No.of test material: F-12676, PDC lot 20
- Expiration date of the lot/batch: 03 September 2013 (allocated by WIL Research Europe B.V., 1 year after receipt of the test substance)
- Purity test date: 99.96%

STABILITY AND STORAGE CONDITIONS OF TEST MATERIAL
- Storage condition of test material: At room temperature in the dark

TREATMENT OF TEST MATERIAL PRIOR TO TESTING
The powdery test substance was moistened with water (Elix, Millipore S.A.S., Molsheim, France), immediately before application, to ensure close contact with the animal's skin. No corrections were made for the purity/composition of the test substance, since the guidelines requires a fixed amounts that has to be dosed.

FORM AS APPLIED IN THE TEST (if different from that of starting material): The powdery test substance was moistened with water (Elix, Millipore S.A.S., Molsheim, France) immediately before application

Test animals

Species:
rabbit
Strain:
New Zealand White
Details on test animals and environmental conditions:
TEST ANIMALS
- Source: Charles River Deutschland, Kisslegg, Germany
- Age at study initiation: At least 6 weeks old
- Weight at study initiation: 1638.3 g (average)
- Housing: Animals were individually housed in labeled cages with perforated floors (Ebeco, Germany, dimensions 67 x 62 x 55 cm) and shelters (Ebeco, Germany, dimensions 40 x 32 x 23 cm)
- Diet (e.g. ad libitum): Diet Pelleted diet for rabbits (Global Diet 2030 from Harlan Teklad®, Mucedola, Milanese, Italy) approximately 100 grams per day. Hay (TecniLab-BMI BV, Someren, The Netherlands) and wooden sticks (Swedish aspen wood, Bioservices, Uden, The Netherlands) were available during the study period
- Water (e.g. ad libitum): Free access to tap water
- Acclimation period: Acclimatization period was at least 5 days before start of treatment under laboratory conditions

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 18 to 24°C
- Humidity (%): 40-70%
- Air changes (per hr): Approximately 15 room air changes/hour
- Photoperiod (hrs dark / hrs light): 12:12 light:dark cycle

IN-LIFE DATES: From: 13 November 2012 To: 22 November 2012

Test system

Type of coverage:
semiocclusive
Preparation of test site:
clipped
Vehicle:
water
Amount / concentration applied:
TEST MATERIAL
- Amount(s) applied (volume or weight with unit): 0.5 g (moistened with 0.5 mL water)
Duration of treatment / exposure:
4 hours
Observation period:
3 days
Number of animals:
3 males
Details on study design:
TEST SITE
- Area of exposure: 2 x 3 cm using a metalline patch
- Type of wrap if used: The patch was mounted on Micropore tape, which was wrapped around the abdomen and secured with Coban elastic bandage

REMOVAL OF TEST SUBSTANCE
- Washing (if done): Skin cleaned of residual test substance using tap water
- Time after start of exposure: 4 hours post application

OBSERVATION TIME POINTS
Skin reactions were assessed at approximately 1, 24, 48, and 72 hours after removal of the dressings and test substance

SCORING SYSTEM:
Erythema and eschar formation:
No erythema .......................................................................................................................... 0
Very slight erythema (barely perceptible) ............................................................................... 1
Well-defined erythema ........................................................................................................... 2
Moderate to severe erythema ................................................................................................. 3
Severe erythema (beet redness) * .......................................................................................... 4
*. Where signs of necrosis or corrosion (injuries in depth) prevent erythema scoring, the maximum grade for erythema (= 4) is given.

Oedema formation:
No oedema ............................................................................................................................ 0
Very slight oedema (barely perceptible) ................................................................................. 1
Slight oedema (edges of area well-defined by definite raising) ............................................... 2
Moderate oedema (raised approximately 1 millimeter) ........................................................... 3
Severe oedema (raised more than 1 millimeter and extending beyond the area of exposure) 4

Results and discussion

In vivo

Resultsopen allclose all
Irritation parameter:
edema score
Basis:
animal: #1, #2, #3
Time point:
24/48/72 h
Score:
0
Max. score:
0
Remarks on result:
no indication of irritation
Irritation parameter:
primary dermal irritation index (PDII)
Basis:
other: #1, #2, #3
Time point:
24/48/72 h
Score:
0
Remarks on result:
no indication of irritation
Irritant / corrosive response data:
No skin irritation (erythema or edema) was caused by 4 hours exposure to the test article.
Other effects:
No staining of the treated skin by the test substance was observed and no test substance remnants were seen. No symptoms of systemic toxicity were observed in the animals during the test period and no mortality occurred.

Applicant's summary and conclusion

Interpretation of results:
GHS criteria not met
Conclusions:
Based on the results of the study (all scores 0, PII=0.0/8.0), the test article is not a skin irritant.
Executive summary:

The skin irritation potential of the test article was evaluated in albino rabbits. The test was conducted under OECD GLP (1997) conditions. The test method was based on OECD No. 404 (2002), EC No. 440 (2008), US EPA, OPPTS 870.2500 (1998), and JMAFF Guidelines (2011). Three male rabbits were exposed to 0.5 grams of the test article moistened with water by application onto clipped skin for 4 hours using a semi-occlusive dressing. Sites were cleaned of residual test substance using tap water after 4 hours of exposure. Animals were observed twice daily for mortality/viability, at least once daily for toxicity, and body weight was taken on the day of treatment (prior to application) and after the final observation. The exposed sites were examined at 1, 24, 48, and 72 hours and scored for erythema and edema. Erythema and edema scores of zero were reported at all time points for all animals (PII=0.0/8.0). Based on the results of the study (all scores 0, PII=0.0/8.0), the test article is not a skin irritant.