Registration Dossier

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:
2006-05-12 to 2005-05-22
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
guideline study
Remarks:
Well-documented, GLP compliant study, performed in accordance with OECD Guideline 404 and Commission Directive 2004/73/EC, B.4. No major deviations were recorded.

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
Test material form:
solid: particulate/powder
Specific details on test material used for the study:
SOURCE OF TEST MATERIAL
- Source and lot/batch No.of test material: 06C0828
- Expiration date of the lot/batch: 2007-03-31 (retest date)
- Purity: 99.9%
- Purity test date: no data

STABILITY AND STORAGE CONDITIONS OF TEST MATERIAL
- Storage condition of test material: at room temperature (range of 20 +/- 5°C), light protected
- Stability under test conditions: no data
- Solubility and stability of the test substance in the solvent/vehicle: no data

TREATMENT OF TEST MATERIAL PRIOR TO TESTING
- Treatment of test material prior to testing: the test item was weighed as delivered by the sponsor and then moistened with approximately 0.5 mL of purified water before application.

Test animals

Species:
rabbit
Strain:
New Zealand White
Details on test animals and environmental conditions:
TEST ANIMALS
- Source: young adult New Zealand White rabbit (SPF), from Harlan France, ZI Le Marlcourlet, 03800 Gannat/France
- Age at treatment: 11 weeks (male), 11-12 weeks (females)
- Weight at first day of acclimatization: 2404 grams (male), 2157-2262 grams (females)
- Housing: standard laboratory conditions, in air-conditoned rooms, individually in stainless steel cages equipped with feed hoppers and drinking water bowls. Wood blocks and haysticks were provided for gnawing. Music was played during the daytime light period.
- Diet (e.g. ad libitum): Pelleted standard Provimi Kliba 3418 rabbit maintenance diet ad libitum provided by Provimi Kliba AG, CH-4303 Kaiseraugst.
- Water (e.g. ad libitum): community tap water from Füllinsdorf, ad libitum.
- Acclimation period: 5 days (2006-05-12 to 2006-05-16), under laboratory conditions after health examinations. Only animals without any visual signs were used for the study.

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

IN-LIFE DATES: From: 2006-05-17 To: 2006-05-22

Test system

Type of coverage:
semiocclusive
Preparation of test site:
clipped
Vehicle:
unchanged (no vehicle)
Controls:
no
Amount / concentration applied:
TEST MATERIAL
- Amount(s) applied (volume or weight with unit): 500 mg
Duration of treatment / exposure:
4 hours
Observation period:
72 hours
Number of animals:
3
Details on study design:
TEST SITE
- Area of exposure: left flank, ca. 4cm x 4cm
- % coverage: no data
- Type of wrap if used: the dressing was wrapped around the abdomen and anchored with tape.

REMOVAL OF TEST SUBSTANCE
- Washing (if done): after removal of the dressing, the skin was flushed with lukewarm tap water to clean the application site.
- Time after start of exposure: 4 hours

OBSERVATION TIME POINTS
- The skin reaction was assessed at approximately 1, 24, 48 and 72 hours after exposure (removal of the dressing, gauze patch and test item).
- To allow further examination of the test site animal No. 51 was re-clipped on completion of the 24-hour examination.

SCORING SYSTEM:
- The skin reaction was assessed according to the numerical scoring system listed in the commission Directive 2004/73/EC, April 29,2004. If evident, corrosive or staining properties of the test item were described and recorded.
- The mean score was calculated across 3 scoring times (24, 48 and 72 hours after patch removal) for each animal for erythema/eschar grades and for oedema grades, separately. An animal is positive when the mean score is 2 or greater. The test is positive for irritation when at least 2 animals are positive for the same endpoint (erythema/eschar or oedema).

Results and discussion

In vivo

Resultsopen allclose all
Irritation parameter:
erythema score
Basis:
mean
Remarks:
animal no. 49 (male)
Time point:
24/48/72 h
Score:
0
Max. score:
4
Reversibility:
other: not applicable
Irritation parameter:
erythema score
Basis:
mean
Remarks:
animal no. 50 (female)
Time point:
24/48/72 h
Score:
0
Max. score:
4
Reversibility:
other: not applicable
Irritation parameter:
erythema score
Basis:
mean
Remarks:
animal no. 51 (female)
Time point:
24/48/72 h
Score:
0
Max. score:
4
Reversibility:
other: not applicable
Irritation parameter:
edema score
Basis:
mean
Remarks:
animal no. 49 (male)
Time point:
24/48/72 h
Score:
0
Max. score:
4
Reversibility:
other: not applicable
Irritation parameter:
edema score
Basis:
mean
Remarks:
animal no. 50 (female)
Time point:
24/48/72 h
Score:
0
Max. score:
4
Reversibility:
other: not applicable
Irritation parameter:
edema score
Basis:
mean
Remarks:
animal no. 51 (female)
Time point:
24/48/72 h
Score:
0
Max. score:
4
Reversibility:
other: not applicable
Irritant / corrosive response data:
The test item did not elicit any skin reactions at the application site of any animal at any of the observation times. The individual mean score for erythema/eschar and oedema for each of the three animals was therefore 0. No staining produced by the test item of the treated skin was observed. 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 the animals 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) and the criteria laid down by the CLP regulation, TIC2782 (T002907) is considered to be “not irritating” to skin.