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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:
2006-06-28 to 2006-07-18
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
guideline study
Remarks:
GLP study conducted according to OECD Guideline 404 and EU Method B.4. with one deviation: the test substance was put on a surgical gauze patch of approximately 4 cm x 4 cm (instead of 6 cm2) to guarantee a good contact and uniform distribution of the test substance on the skin. This deviation, however, did not affect the validity of this study.

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:
yes
Remarks:
The testing facility reported the following deviations: the test item was put on a surgical gauze patch of approximately 4 cm x 4 cm (instead of 6 cm2) to guarantee a good contact and uniform distribution of the test item on the skin.
Qualifier:
according to
Guideline:
EU Method B.4 (Acute Toxicity: Dermal Irritation / Corrosion)
Deviations:
yes
Remarks:
The testing facility reported the following deviations: the test item was put on a surgical gauze patch of approximately 4 cm x 4 cm (instead of 6 cm2) to guarantee a good contact and uniform distribution of the test item on the skin.
GLP compliance:
yes (incl. certificate)
Remarks:
Certificate from the Swiss GLP Monitoring Authorities

Test material

Reference
Name:
Unnamed
Type:
Constituent
Test material form:
solid: particulate/powder
Details on test material:
White to light yellow powder
Specific details on test material used for the study:
SOURCE OF TEST MATERIAL
- Source and lot/batch No.of test material: 00405251ZT000841PUA421
- Expiration date of the lot/batch: 2007-06-30
- Purity test date: no data

STABILITY AND STORAGE CONDITIONS OF TEST MATERIAL
- Storage condition of test material: room temperature (range of 20 +/- 5 deg C), light protetected
- Stability under test conditions: no data
- Solubility and stability of the test substance in the solvent/vehicle: no data
- Reactivity of the test substance with the solvent/vehicle of the cell culture medium: no data

Test animals

Species:
rabbit
Strain:
New Zealand White
Details on test animals and environmental conditions:
TEST ANIMALS
- Source: Harlan Netherlands BV Kreuzelweg 53 NL-5961 NM Horst/The Netherlands
- Age at study initiation: 10 weeks
- Weight at study initiation: 2139 to 2407 grams
- 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) provided by Provimi Kliba AG, CH-4303 Kaiseraugst.
- Water (e.g. ad libitum): Community tap water from Fullinsdorf, ad libitum.
- Acclimation period: 2006-06-28 to 2006-07-02 (one female), and 2006-06-28 to 2006-07-03 (one male and one female)

ENVIRONMENTAL CONDITIONS
- Temperature (deg C): 17-23 deg C
- Humidity (%): 30-70%
- Air changes (per hr): 10-15 per hour
- Photoperiod (hrs dark / hrs light): 12/12
-Other: Music was played during the daytime light period.


IN-LIFE DATES: From: 2006-07-03 (one female) and 2006-07-04 (one female and one male) To: 2006-07-18

Test system

Type of coverage:
semiocclusive
Preparation of test site:
clipped
Vehicle:
unchanged (no vehicle)
Controls:
other: Untreated skin areas were used as control.
Amount / concentration applied:
TEST MATERIAL
- Amount(s) applied (volume or weight with unit): 0.5 g of test substance
- Concentration (if solution): no data
- Other: pH was measured before the study initiation date. A forumulation of a 1% (w/w) solution was prepared. The pH was found to be 9.19.


VEHICLE
no data
Duration of treatment / exposure:
single dose for 4-hour treatment
Observation period:
1, 24, 48, and 72 hours, as well as 7, 10, and 14 days
Number of animals:
1 male and 2 females
Details on study design:
TEST SITE
- Area of exposure: The left flank was clipped with an electric clipper, exposing an area of approximately 100 cm2 (10 cm x 10 cm). The test substance was applied with a 4 cm x 4 cm surgical gauze patch. The gauze patch was applied to the intact skin of the clipped area.
- % coverage: no data
- Type of wrap if used: The patch was covered with a semi-occlusive dressing. The dressing was wrapped around the abdomen and anchored with tape.


REMOVAL OF TEST SUBSTANCE
- Washing (if done): Washed in lukewarm tap water to clean the application site so that any reactions (erythema) were clearly visible at the time.
- Time after start of exposure: 4 hours


SCORING SYSTEM:
-The skin reaction was assessed according to the numerical scoring system listed in the Commission Directive 2004/79/EC, April 29, 2004. If evident, corrosive or staining properties of the test substance were described and recorded.

Observations:
Viability/Mortality: daily from acclimatization of the animals to the termination of the test.
Clinical signs (local/systemic): daily from acclimatization of the animals to the termination of the test.
Body weights: at start of acclimatization start, on the day of application and termination of observation.

Results and discussion

In vivo

Resultsopen allclose all
Irritation parameter:
erythema score
Basis:
mean
Remarks:
; animals number 49, 50, and 51
Time point:
24/48/72 h
Score:
2
Max. score:
4
Reversibility:
not fully reversible within: 14 days
Remarks on result:
other: Clipped area
Irritation parameter:
edema score
Basis:
mean
Remarks:
; animal number 49 (male)
Time point:
24/48/72 h
Score:
2
Max. score:
4
Reversibility:
fully reversible within: 7 days
Remarks on result:
other: Clipped area
Irritation parameter:
edema score
Basis:
mean
Remarks:
; animal number 50 (female)
Time point:
24/48/72 h
Score:
0.33
Max. score:
4
Reversibility:
fully reversible within: 48 hours
Remarks on result:
other: Clipped area
Irritation parameter:
edema score
Basis:
mean
Remarks:
; animal number 51 (female)
Time point:
24/48/72 h
Score:
1.67
Max. score:
4
Reversibility:
fully reversible within: 7 days
Remarks on result:
other: Clipped area
Irritant / corrosive response data:
In addition to the erythema, a very slight swelling was noted in each of the three rabbits at the 1-hour reading. In one animal, the swelling persisted as very slight at the 24-hour reading and disappeared thereafter, whereas two animals expressed a slight swelling at the 24- and 48-hour readings. At the 72-hour reading, the swelling was still slight in one animal and very slight in one animal, respectively.

In one animal, necrosis was noted at the application site from the 24-hour reading up to 10 days after the treatment, but was no longer noted 14 days after the treatment, at the termination.

Scaling of the treated skin was observed in two animals from the 48-hour reading until the termination, and in one animal from the 7-day reading to the termination.

The study was terminated 14 days after the treatment as planned, even though full reversibility of the skin effects could not be observed during this period.

Neither alterations of the treated skin were observed, nor were corrosive effects evident on the skin.
Other effects:
- Visibility/Mortality/Clinical Signs: No clinical signs of systemic toxicity were observed in the animals during the study and no mortality occurred.
- Coloration: No staining produced by the test substance of the treated skin was observed.
- Body Weight: The body weights of all rabbits were considered to be within the normal range of variability.

Applicant's summary and conclusion

Interpretation of results:
GHS criteria not met
Conclusions:
Based upon the referred classification criteria (Commission Directive 2001/59/EC of August 2001), the test substance is considered to be “irritating” to rabbit skin.
However, based on the criteria of CLP regulation, the substance should not be classified as the mean score over 24h,48h,72h is below the cut off value of 2.3 for all animals