Registration Dossier

Administrative data

Endpoint:
skin irritation: in vivo
Type of information:
experimental study
Adequacy of study:
key study
Study period:
September 27 - October 06, 2006
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
other: The study has been performed according to OECD and/or EC guidelines and according to GLP principles. Period of exposure was 24h instead of 4h.

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
2006
Report Date:
2006

Materials and methods

Test guidelineopen allclose all
Qualifier:
according to
Guideline:
OECD Guideline 404 (Acute Dermal Irritation / Corrosion)
Deviations:
no
Qualifier:
according to
Guideline:
EU Method B.4 (Acute Toxicity: Dermal Irritation / Corrosion)
Deviations:
no
GLP compliance:
yes (incl. certificate)

Test material

Reference
Name:
Unnamed
Type:
Constituent
Details on test material:
- Name of test material (as cited in study report): CH-CA
- Description: Colorless clear liquid
- Storage condition of test material: At room temperature (range of 20 ± 5°C), light protected
- Stability under storage conditions: Stable under storage conditions

Test animals

Species:
rabbit
Strain:
New Zealand White
Details on test animals and environmental conditions:
- Source: Harlan Netherlands BV, Kreuzelweg 53, NL-5961 NM horst, The Netherlands
- Age at study initiation: 12 weeks (male), 11 weeks (females)
- Weight at study initiation: 2737 g (male, 2398 and 2432 (females)
- Housing: Individually in stainless steel cages equipped with feed hoppers and drinking water bowls. Wood blocks (RCC Ltd, Fullinsdorf) and haysticks 4642 (batch no. 77/05, Provimi Kliba AG) were provided for gnawing.
- Diet (e.g. ad libitum): Pelleted standard Provimi Kliba 3418 rabbit maintenance diet ad libitum (batch no. 24/06 and 51/06) provided by Provimi Kliba AG, CH-4303 Kaiseraugst. Results of analysis for contaminants are archived at RCC Ltd.
- Water (e.g. ad libitum): Community tap water from Fullinsdorf, ad libitum. Results of bacteriological, chemical and contaminant analyses are archived at RCC Ltd.
- Acclimation period: The acclimatization period was at least 5 days before the start of treatment.

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 17 – 23ºC
- Humidity (%): 30 - 70%
- Air changes (per hr): approximately 10-15 air changes per hour
- Photoperiod (hrs dark / hrs light): 12 hours dark/12 hours light.

Test system

Type of coverage:
semiocclusive
Preparation of test site:
other: shaved 24 hours before treatment
Vehicle:
unchanged (no vehicle)
Controls:
other: Adjacent areas of the untreated skin of each animal served as controls.
Amount / concentration applied:
TEST MATERIAL
- Amount(s) applied (volume or weight with unit): 0.5 mL (per animal)

Duration of treatment / exposure:
24 hours (single application)
Observation period:
1, 24, 48 and 72 hours after treatment
Number of animals:
1 male and 2 females.
Details on study design:
TEST SUBSTANCE PREPARATION
0.5 mL (per animal) of CH-CA was measured with a syringe and applied undiluted as it was delivered by the Sponsor. The pH of the test item was measured before the study initiation date and was found to be 5.

TEST SITE
Four days before treatment, the left flank was clipped with an electric clipper, exposing an area of approximately 100 cm^2 (10 cm x 10 cm). the skin of the animals was examined one day before treatment, and regrown fur of all animals was clipped again.

On the day of treatment, 0.5 mL of CH-CA was placed on a surgical gauze patch (ca. 2.5 cm x 2.5 cm). This gauze patch was applied to the intact skin of the clipped area. The patch was covered with a semi-occlusive dressing. The dressing was wrapped around the abdomen and anchored with tape.

REMOVAL OF TEST SUBSTANCE
The skin was flushed with lukewarm tap water.

OBSERVATIONS
- Mortality/Viability: Daily from acclimatization of the animals to the termination of the test.
- Clinical signs: Daily from acclimatization of the animals to the termination of the test.
- Body Weight: At start of acclimatization, on the day of application and at termination of observation.
- Irritation:
The skin reactions were assessed at approximately 1, 24, 48 and 72 hours after exposure.

SCORING SYSTEM:
The irritation was assessed according to the following numerical scoring system. At each observation, the highest scores given were recorded:

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

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

Results and discussion

In vivo

Resultsopen allclose all
Irritation parameter:
erythema score
Basis:
mean
Remarks:
animal #1 and #3
Time point:
other: 24, 48 and 72 hours.
Score:
0
Max. score:
4
Irritation parameter:
erythema score
Basis:
animal #2
Remarks:
(mean)
Time point:
other: 24, 48 and 72 hours.
Score:
0.33
Max. score:
4
Reversibility:
fully reversible within: 48 hours
Irritation parameter:
edema score
Basis:
mean
Remarks:
animal #1, #2 and #3
Time point:
other: 24, 48 and 72 hours.
Score:
0
Max. score:
4
Irritant / corrosive response data:
The mean erythema/eschar score of the three animals was 0, 0.33 and 0, respectively and the mean oedema score was 0.00 for each of the three animals. The primary irritation index was 0.11 (max 8.0).
Mild erythema was observed one hour after removal of the test item patch in two of the three treated animals and persisted in one animal still at the 24-hour reading.
Neither alterations of the treated skin were observed nor were corrosive effects evident on the skin.
Other effects:
No clinical signs of systemic toxicity were observed in the animals during the study and no mortality occurred.
The body weights of all rabbits were considered to be within the normal range of variability.

Applicant's summary and conclusion

Interpretation of results:
not irritating
Remarks:
Migrated information Criteria used for interpretation of results: EU
Conclusions:
In a skin irritation test performed according to OECD 404 and GLP, the test substance, CH-CA, is considered to be not irritating to rabbit skin.