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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:
2004-01-05 to 2004-03-16
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
other: GLP guidelines study reliable without restrictions

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
2004
Report date:
2004

Materials and methods

Test guidelineopen allclose all
Qualifier:
according to guideline
Guideline:
EU Method B.4 (Acute Toxicity: Dermal Irritation / Corrosion)
Qualifier:
according to guideline
Guideline:
OECD Guideline 404 (Acute Dermal Irritation / Corrosion)
Version / remarks:
adopted 2002-04-24
Principles of method if other than guideline:
No systemic effects were recorded; tabulation of irritation / corrosion response scores for each animal at all time points measured was not given, only for the time points up to 72 hours.
GLP compliance:
yes (incl. QA statement)
Remarks:
signed 2003-06-04

Test material

Constituent 1
Chemical structure
Reference substance name:
-
EC Number:
480-070-0
EC Name:
-
Cas Number:
85-27-8
Molecular formula:
C14H14O2
IUPAC Name:
4-(1-phenylethyl)benzene-1,3-diol
Details on test material:
- Name of test material: BIO 377
- Chemical name: 1,3-Benzenediol, 4-(1-phenylethyl)-
- Physical state: clear, viscous to solid (observation of the study direction: test item was viscous and sticky after warming up)
- Storage condition of test material: cool, dry, dark
- Solubility: 50 % in Mygliol (neutral oil) = well soluble; 50 % in peanut oil (conditionally soluble); 20 % in peanut oil (well soluble)

Test animals

Species:
rabbit
Strain:
other: Chbb:HM (SPF) - Littlerussian
Details on test animals or test system and environmental conditions:
TEST ANIMALS
- Source: DIMED Schönwalde GmbH, 16352 Schönwalde
- Weight at study initiation: 2.5 kg - 3.0 kg
- Housing: rabbits were caged individually in PPO cages (floor area: 2576 sq. cm) with perforated floor.
- Diet (ad libitum): a pelleted complete rabbit diet "Altromin 2123" from Altromin, D-32791 Lage, Lippe, Germany
- Water (ad libitum): domestic quality drinking water acidified with hydrochloric acid to pH 2.5 in order to prevent microbial growth.
- Acclimation period: at least one week

ENVIRONMENTAL CONDITIONS - provision of filtered air
- Temperature: 20 °C +/- 3 °C
- Relative humidity: 55 % +/- 15 %
- Air changes: 10 times/hour
- Photoperiod (hrs dark / hrs light): 12/12

Test system

Type of coverage:
semiocclusive
Preparation of test site:
other: clipped
Vehicle:
unchanged (no vehicle)
Controls:
no
Amount / concentration applied:
For the undiluted application the test item was warmed up to max. 90 °C in the provided aluminium container in order to reduce its viscosity and to make the taking off easier. An amount of 0.5 g of the viscous and sticky test item was put on the patch and applied to the prepared skin after the cooling down. After termination of exposure the patch and sticky residues of the test item were removed by cleansing the skin with peanut oil.

Duration of treatment / exposure:
100 % (v/v) of the test item: 1 hour (only initial test with one rabbit was conducted due to corrosive effects)

Observation period:
immediately and 1 h., 24 h., 48 h., as well as 72 h. after the termination of exposure as well as on day 7, 14, 21 and 28
Number of animals:
100 % (v/v) of the test item: 1 female rabbit
Details on study design:
TEST SITE
- Area of exposure: the day before the treatment the skin area on the back was clipped as closely as possible with an electric clipper.

INITIAL TEST:
On the experimental day the rabbit was physically restrained on a test table and the back was divided in six test fields. One side of the body served as the test area for the test item.
An amount of 0.5 g of the test item was applied to a 16-layer gauze patch (2.5 X 2.5 cm), the patch was placed on the appropriate anterior test field and secured semi-occlusively with adhesive Gothaplast tape (2.5 cm). After an exposure time of 3 min. the first patch was removed, the test field was marked and the treated skin was cleaned with peanut oil or mild soap and lukewarm water. A first assessment of the skin reaction took place immediately after the termination of exposure.
Since no corrosive effect were observed at any case a second patch with 0.5 g test item was applied on the median test field of the rabbit back. In order to improve the patch securing the trunk of the animal was additionally wound with 5 cm wide adhesive Gothaplast tape. After an exposure time of 1 h. the second patch was removed and the test field was marked. The 100 % test item was not visible any more and seemed to be diffused into the skin. The skin reaction was first assessed immediately after the termination of exposure.
One hour after the 100 % application signs for corrosive effects were observed and it was decided according to the agreement with the sponsor to stop the test at this time and to renounce the 4-hour exposure.

SCORING SYSTEM: according to the Draize scale

OBSERVATIONS:
The day before the treatment the rabbits were weighed.

Results and discussion

In vivo

Resultsopen allclose all
Irritation parameter:
erythema score
Basis:
mean
Remarks:
animal #1
Time point:
other: 24, 48 and 72 hours
Score:
0.33
Max. score:
4
Reversibility:
fully reversible within: 48 hours
Remarks on result:
other: Observation after an exposure of 3 minutes (100% test item concentration).
Irritation parameter:
erythema score
Basis:
mean
Remarks:
animal #1
Time point:
other: 24, 48 and 72 hours
Score:
4
Max. score:
4
Reversibility:
fully reversible within: 28 days
Remarks on result:
other: Observation after 1h exposure. Test item was not visible anymore & seemed to be diffused into the skin. The skin was white & appeared to be cauterised. The 4h exposure was renounced & the treatment was stopped. Dark brown test area (100% test item).
Irritation parameter:
edema score
Basis:
mean
Remarks:
animal #1
Time point:
other: 24, 48 and 72 hours
Score:
0
Max. score:
4
Remarks on result:
other: Observation after an exposure of 3 minutes (100% test item concentration).
Irritation parameter:
edema score
Basis:
mean
Remarks:
animal #1
Time point:
other: 24, 48 and 72 hours
Score:
2
Max. score:
4
Remarks on result:
other: Observation after 1 h exposure (100% test item concentration).
Irritant / corrosive response data:
TEST CONCENTRATION: 100 % (V/V)

The animal used in the initial test showed a very slight oedema and white skin appearing to be cauterised because the test item seemed to be diffused into the skin and was not visible any more on the middle right test field immediately after the application.

1h. after the termination of exposure a very slight erythema was observed on the anterior right test field of the animal. On the middle right test field the test item seemed to be diffused into the skin. The treated skin was white, appeared to be cauterised and showed a slight oedema.

24 h. after the termination of exposure a very slight erythema was observed on the anterior right test field as well as a severe erythema to eschar formation and a slight oedema on the middle right test field.

48 and 72 hours after termination of exposure the animal showed a severe erythema to eschar formation, a slight oedema and a dark brown colour on the whole middle right test field.

7 days after the termination of exposure white scales were observed on the anterior right test field of the animal. The middle right test field showed a strong, brown crust of scales with a thickness of about 2 mm and top layers coming off on the whole area.

14 days after the termination of exposure isolated scales were observed on the anterior right test field as well as necrotic tissue with a healing full thickness destruction of the skin on the middle right test field.

21 days after the termination of exposure the animal still showed healing tissue on the middle right test field, whereas the anterior right test field was free of any skin reactions.

28 days after the termination of exposure the middle right test field of the animal was free of any signs of skin irritation, too.
Mean values of erythema and oedema formation could not be calculated because the 4-hour exposure was not carried out for ethical reasons.

Any other information on results incl. tables

TEST CONCENTRATION: 25 % (V/V)

The animal used in the initial test showed a very slight erythema and a very slight oedema on the middle left test field as well as a moderate oedema on the posterior left test field immediately after the application.

1 h. after the termination of exposure a very slight erythema and a very slight oedema were observed on the middle left field of the animal used in the initial test as well as a moderate oedema on the posterior left test field. The two animals used in the confirmatory test showed a very slight erythema and a moderate oedema on the anterior right test fields.

24 h. after the termination of exposure a well defined erythema was observed on the middle left test field of the animal used in the initial test and a moderate to severe erythema on the posterior left test field. One animal used in the confirmatory test showed a moderate to severe, brownish erythema and a very slight oedema on the anterior right test field. A well defined, brownish erythema and a very slight oedema were observed in the second animal used in the confirmatory test.

48 h. after the termination of exposure the animal used in the initial test showed a well defined erythema and a very slight oedema on the middle left test field as well as a moderate to severe erythema and a very slight oedema on the posterior left test field. A moderate to severe, brownish erythema and a slight oedema were observed on the anterior right test field of one animal used in the confirmatory test. The second animal used in the confirmatory test showed a well defined, brownish erythema and a very slight oedema on the anterior right test field.

72 h. after termination of exposure a well defined erythema and a very slight oedema were observed in the middle left test field of the animal used in the initial test as well as a moderate to severe erythema and a very slight oedema on the posterior left test field . One animal used in the confirmatory test showed a severe erythema to eschar formation and a slight oedema on the anterior right test field. A moderate to severe erythema and a very slight oedema were observed on the anterior right test field of the second animal used in the confirmatory test.

7days after the termination of exposure the animal used in the initial test showed a thin crust of scales on the whole middle left test field as well as a brown crust on the posterior left test field. A thick crust coming off partially and necrotic tissue underneath were observed on the anterior right test field of one animal used in the confirmatory test. The second animal used in the confirmatory test showed a thin crust on the whole anterior right test field.

14 days after the termination of exposure isolated scales were observed on the middle left test field of the animal used in the initial test. The crust had come off the posterior left test field and healing, necrotic tissue was discernible. The animals used in the confirmatory test showed healing, shining, thin tissue on the anterior right test field.

21 days after the termination of exposure all animals were free of any signs of skin irritation.

The mean individual erythema scores after 4-hour exposure were 3.00, 3.33, 2.33, respectively.

The mean individual oedema scores after 4-hour exposure were 0.67, 1.67, 1.00, respectively.

TEST CONCENTRATION: 5 % (V/V)

The animal used in the initial test showed no skin reactions immediately after the application.

1 h. after the termination of exposure a very slight erythema was observed on the anterior left test field of one animal used in the confirmatory test. The animal used in the initial test and the second animal used in the confirmatory test did not show any skin reactions.

24 h. after the termination of exposure a well defined erythema and a very slight oedema were observed on the middle and posterior left test field of the animal used in the initial test. The animals used in the confirmatory test showed only a very slight erythema on the anterior left test field.

48 and 72 h. after the termination of exposure a well defined erythema and a very slight oedema were observed on the middle left test field of the animal used in the initial test as well as a well defined erythema on the posterior left test field, whereas the animals of the confirmatory test did not show any skin reactions.

7 days after the termination of exposure scales were still observed on all three test fields of the animal used in the initial test.

14 days after the termination of exposure the animal used in the initial test was also free of any signs of skin irritation.

The mean individual erythema scores after 4-hour exposure were 2.00, 0.33, 0.33, respectively.

The mean individual oedema scores after 4-hour exposure were 0.33, 0.00, 0.00, respectively.

Applicant's summary and conclusion

Interpretation of results:
Category 1B (corrosive)
Remarks:
Migrated information Criteria used for interpretation of results: EU
Conclusions:
SymWhite 377 is corrosive to the skin.
According to the EC-Commission directive 67/548/EEC and its subsequent amendments, the test substance is corrosive to the skin.
According to the EC-Regulation 1272/2008 and subsequent regulations, the test item is classified as Category 1B.