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Toxicological information

Skin irritation / corrosion

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Administrative data

Endpoint:
skin irritation: in vivo
Type of information:
migrated information: read-across from supporting substance (structural analogue or surrogate)
Adequacy of study:
key study
Study period:
from Dec. 11, 2001 to Jan. 29, 2002
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
other: see 'Remark'
Remarks:
The study was performed according to test guideline in compliance with GLP with FAT 41030 a structural analogue of FAT 41045. Both substances are very similar in their chemical structure and, as demonstrated, in a number of physicochemical properties. Therefore, this study is used for read-across thus avoiding duplicate tests.

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
2002
Report Date:
2002

Materials and methods

Test guideline
Qualifier:
according to
Guideline:
OECD Guideline 404 (Acute Dermal Irritation / Corrosion)
Deviations:
no
GLP compliance:
yes (incl. certificate)

Test material

Reference
Name:
Unnamed
Type:
Constituent
Test material form:
solid: particulate/powder
Remarks:
migrated information: powder
Details on test material:
FAT 41'030/A

Test animals

Species:
rabbit
Strain:
New Zealand White
Details on test animals and environmental conditions:
Test system New Zealand White Rabbit, SPF
Rationale Recognized by the international guidelines as the recommended test system
Source Elevage Scientifique des Dombes F-01400 Chatillon sur Chalaronne I France
Number of animals per test 3 (Animals of both sexes were used)
Age at start of treatment 10-11 weeks (male) 13-14 weeks (females)
Identification by unique cage number and corresponding ear number.
Acclimatization under laboratory conditions after health examination. Only animals without any visual signs of iIIness were used for the study.
Allocation Male No. 70 Female Nos. 71 and 72
Room no. 106/ RCC Ud, Füllinsdorf
Conditions Standard Laboratory Conditions
Air-conditioned with target ranges for room temperature 17-23 °C, relative humidity 30-70 % and approximately 10-15 air changes per hour. Room temperature and humidity were monitored continuously and values outside of these ranges may have occasionally occurred, usually following room cleaning. These transient variations are considered not to have any influence on the study and, therefore, these data are not reported but are retained at RCC. The animals were provided with an automatically controlled light cycle of 12 hours light and 12 hours dark. Music was played during the light period.
Accommodation Individually in stainless steel cages equipped with feed hoppers, drinking water bowls, with wood (RCC Ud, Füllinsdorf) and haysticks for gnawing.
Diet Pelleted standard Provimi Kliba 3418 rabbit maintenance diet ad libitum (batch no. 93/01) provided by Provimi Kliba AG, CH-4303 Kaiseraugst. Results of analysis are archived at RCC Ud, Itingen.
Haysticks (QS no. 125/01) provided by Eberle Nafag AG, CH-9200 Gossau.
Water Community tap water from Füllinsdorf, ad libitum. Results of bacteriological, chemical and contaminant analyses are archived at RCC Ud, Itingen.

Test system

Type of coverage:
semiocclusive
Preparation of test site:
clipped
Vehicle:
water
Controls:
yes, concurrent vehicle
Amount / concentration applied:
0.5 g (per animal)
Duration of treatment / exposure:
4 h
Observation period:
Throughout 14 days after treatment
Number of animals:
3
Details on study design:
Four days before treatment, one flank was clipped with an electric clipper, exposing an area of approximately 100 cm2 (10 cm x 10 cm). The skin of the animals was examined one day before treatment, and regrown fur of all animals was again clipped.
Animals with overt signs of skin injury or marked irritation which may have interfered with the interpretation of the results were not used in the test. On the day of treatment, 0.5 g of FAT 41'030/A was placed on a surgical gauze patch (ca. 4 cm x 4 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.
The duration of treatment was 4 hours. Then the dressing was removed and the skin was flushed with lukewarm tap water to clean the application site so that any reactions (erythema) were clearly visible at that time.
The test sites of all animals were again washed on completion of the 24-hour examination in an attempt to remove the marked red staining caused by the test item.

Results and discussion

In vivo

Resultsopen allclose all
Irritation parameter:
overall irritation score
Basis:
mean
Time point:
other: 24-72 hours
Score:
0
Max. score:
8
Reversibility:
other: not applicable
Irritation parameter:
erythema score
Basis:
mean
Time point:
other: 1 h
Max. score:
4
Reversibility:
other: not applicable
Remarks on result:
other: staining of the skin prevented assessment
Irritation parameter:
erythema score
Basis:
mean
Time point:
other: 24 h
Score:
0
Max. score:
4
Reversibility:
other: not applicable
Remarks on result:
other: staining of the skin prevented assessment
Irritation parameter:
erythema score
Basis:
mean
Time point:
other: 48 h
Score:
0
Max. score:
4
Reversibility:
other: not applicable
Remarks on result:
other: staining of the skin in 2 animals prevented assessment
Irritation parameter:
erythema score
Basis:
mean
Time point:
other: 72 h
Score:
0
Max. score:
4
Reversibility:
other: not applicable
Irritation parameter:
edema score
Basis:
mean
Time point:
other: 1 h
Score:
0
Max. score:
4
Reversibility:
other: not applicable
Irritation parameter:
edema score
Basis:
mean
Time point:
other: 24 h
Score:
0
Max. score:
4
Reversibility:
other: not applicable
Irritation parameter:
edema score
Basis:
mean
Time point:
other: 48 h
Score:
0
Max. score:
4
Reversibility:
other: not applicable
Irritation parameter:
edema score
Basis:
mean
Time point:
other: 72 h
Score:
0
Max. score:
4
Reversibility:
other: not applicable
Irritant / corrosive response data:
Assessment of erythema was prevented on a number of occasions due to a marked red staining at the test site. Where evaluation was permitted, no signs of irritation (erythema or oedema) were observed.
The mean oedema score was calculated across 3 scoring times (24, 48 and 72 hours after patch removal) for each animal. The mean oedema score was 0.00. A mean value for erythema could not be calculated across the three readings due to insufficient data.
Other effects:
No clinical signs of systemic toxicity were observed in the animals during the study and no mortality occurred.
A marked red staining was present on the test site of all animals from 1 to 72 hours after treatment and was still evident in two animals at the 7-day reading. Slight staining continued to be observed in all animals du ring the observation period and was still evident 14 days after treatment, the end of the observation period for all animals.
With the exception of the persistent red staining, no irreversible alterations of the treated skin were observed nor were corrosive effects evident on the skin.
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 classified
Remarks:
Migrated information Criteria used for interpretation of results: EU
Conclusions:
Based on the results given in this study, test item is considered to be not irritating to rabbits' skin.
Executive summary:

This primary skin irritation study was conducted to assess the possible irritation potential by topical semi-occlusive application of 0.5 g to the intact left flank of each of three young adult New Zealand White rabbits. The duration of treatment was four hours. The scoring of skin reactions was performed at 1, 24, 48 and 72 hours, as well as 7, 10 and 14 days after removal of the dressing. The mean oedema score was calculated across 3 scoring times (24, 48 and 72 hours after patch removal) for each animal. The mean oedema score was 0.00. A mean value for erythema could not be calculated ac ross the three readings due to insufficient data. The application of FAT 41030/A to the skin resulted in a marked red staining on the test site of all animals. The severity of the staining gradually decreased but was still present at the test site of all animals 14 days after treatment, the end of the observation period. No signs of irritation (erythema or oedema) were observed. No corrosive effects were noted on the treated skin of any animal at any measuring interval. Thus, the test item did not induce significant damage to the rabbit skin.