Registration Dossier

Toxicological information

Skin irritation / corrosion

Currently viewing:

Administrative data

Endpoint:
skin irritation: in vivo
Type of information:
experimental study
Adequacy of study:
key study
Study period:
04.11 - 25.11. 2003
Reliability:
1 (reliable without restriction)

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:
OECD Guideline 404 (Acute Dermal Irritation / Corrosion)
Deviations:
yes
Remarks:
Deviations from the minimum level of temperature occurred. Based on laboratory historical data these deviations were considered not to have affected the study integrity.
Qualifier:
according to guideline
Guideline:
EPA OPPTS 870.2500 (Acute Dermal Irritation)
GLP compliance:
yes (incl. QA statement)

Test material

Constituent 1
Chemical structure
Reference substance name:
4-chlororesorcinol
EC Number:
202-462-0
EC Name:
4-chlororesorcinol
Cas Number:
95-88-5
Molecular formula:
C6H5ClO2
IUPAC Name:
4-chlorobenzene-1,3-diol
Test material form:
other:
Remarks:
beige powder
Details on test material:
Molecular weight: 144.65

Test animals

Species:
rabbit
Strain:
New Zealand White
Details on test animals or test system and environmental conditions:
Age: at least 6 weeks
Body weight: at least 1.0 kg
Conditions:
Animals were housed in a controlled environrnent, in which optimal conditions were considered to be approximately 15 air changes per hour, a temperature of 21.0 I 3.0°C (actual range: 17.9- 21.2°C), a relative humidity of 30-70% (actual range: 41 - 74%) and 12 hours artificial
fluorescent light and 12 hours darkness per day. Cleaning procedures in the room might have caused the temporary fluctuations above the optimal maximum level of 70% for relative humidity. Based on laboratory historical data, these fluctuations were considered not to have
affected the study integrity.
Accommodation:
Individually in labelled cages with perforated floors (Scanbur, Denmark, dimensions 56~44~37c.m5 ). Acclimatisation period was at least 5 days before start of treatment under laboratory conditions.
Diet:
Standard laboratory rabbit diet, approx. 100 g/day.
Water:
Free access to tap-water.

Test system

Type of coverage:
semiocclusive
Preparation of test site:
clipped
Vehicle:
other: powdery test substance was moistened with water
Amount / concentration applied:
0.5 g test substance was moistened with 0.6 ml Milli U
Duration of treatment / exposure:
4 h
Observation period:
14 d
Number of animals:
3 males
Details on study design:
Approximately 24 hours before treatrnent, the dorsal fur was clipped with electric clippers, exposing an area of approximately 150 Square centimeters (10x15 cm2). Whenever considered necessary the treated skin areas were re-clipped at least 3 hours before the observations, to facilitate scoring.

A health inspection was performed prior to the commencement of treatment, to ensure that the animals were in a good state of health. Special attention was paid to the Skin to be treated, which was intact and free frorn abnorrnalities.

Each animal was treated by dermal application of 0.5 grams of the test substance. The test substance was moistened with 0.6 ml Milli U water and applied to the skin of one flank, using a metalline patch of 2x3 cm. The patch was mounted on Micropore tape, which was wrapped around the abdomen and secured with Coban elastic bandage.

Four hours after the application, the dressing was rernoved and the skin cleaned of residual test substance using water and ethanol.

Results and discussion

In vivo

Resultsopen allclose all
Irritation parameter:
erythema score
Basis:
animal #1
Time point:
other: 1 h
Score:
1
Max. score:
4
Remarks on result:
other: brown staining of the skin by the test substance
Irritation parameter:
erythema score
Basis:
animal #1
Time point:
24 h
Score:
1
Max. score:
4
Remarks on result:
other: brown staining of the skin by the test substance
Irritation parameter:
erythema score
Basis:
animal #1
Time point:
48 h
Score:
1
Max. score:
4
Remarks on result:
other: brown staining of the skin by the test substance
Irritation parameter:
erythema score
Basis:
animal #1
Time point:
72 h
Score:
1
Max. score:
4
Remarks on result:
other: brown staining of the skin by the test substance; reduced flexibility of the skin
Irritation parameter:
erythema score
Basis:
animal #1
Time point:
7 d
Score:
0
Max. score:
4
Remarks on result:
other: brown staining of the skin by the test substance; bald skin; scaliness
Irritation parameter:
erythema score
Basis:
animal #1
Time point:
14 d
Score:
0
Max. score:
4
Remarks on result:
other: brown staining of the skin by the test substance; scaliness
Irritation parameter:
edema score
Basis:
animal #1
Time point:
other: 1 h
Score:
2
Max. score:
4
Remarks on result:
other: brown staining of the skin by the test substance
Irritation parameter:
edema score
Basis:
animal #1
Time point:
24 h
Score:
2
Max. score:
4
Remarks on result:
other: brown staining of the skin by the test substance
Irritation parameter:
edema score
Basis:
animal #1
Time point:
48 h
Score:
2
Max. score:
4
Remarks on result:
other: brown staining of the skin by the test substance
Irritation parameter:
edema score
Basis:
animal #1
Time point:
72 h
Score:
3
Max. score:
4
Remarks on result:
other: brown staining of the skin by the test substance; reduced flexibility of the skin
Irritation parameter:
edema score
Basis:
animal #1
Time point:
7 d
Score:
0
Max. score:
4
Remarks on result:
other: brown staining of the skin by the test substance; bald skin; scaliness
Irritation parameter:
edema score
Basis:
animal #1
Time point:
14 d
Score:
0
Max. score:
4
Remarks on result:
other: brown staining of the skin by the test substance; scaliness
Irritation parameter:
erythema score
Basis:
animal #2
Time point:
other: 1 h
Score:
1
Max. score:
4
Remarks on result:
other: brown staining of the skin by the test substance
Irritation parameter:
erythema score
Basis:
animal #2
Time point:
24 h
Score:
1
Max. score:
4
Remarks on result:
other: brown staining of the skin by the test substance
Irritation parameter:
erythema score
Basis:
animal #2
Time point:
48 h
Score:
2
Max. score:
4
Remarks on result:
other: brown staining of the skin by the test substance
Irritation parameter:
erythema score
Basis:
animal #2
Time point:
72 h
Score:
3
Max. score:
4
Remarks on result:
other: brown staining of the skin by the test substance; reduced flexibility of the skin
Irritation parameter:
erythema score
Basis:
animal #2
Time point:
7 d
Score:
2
Max. score:
4
Remarks on result:
other: brown staining of the skin by the test substance; reduced flexibility of the skin; scaliness
Irritation parameter:
erythema score
Basis:
animal #2
Time point:
14 d
Score:
1
Max. score:
4
Remarks on result:
other: bald skin
Irritation parameter:
edema score
Basis:
animal #2
Time point:
other: 1 h
Score:
3
Max. score:
4
Remarks on result:
other: brown staining of the skin by the test substance
Irritation parameter:
edema score
Basis:
animal #2
Time point:
24 h
Score:
2
Max. score:
4
Remarks on result:
other: brown staining of the skin by the test substance
Irritation parameter:
edema score
Basis:
animal #2
Time point:
48 h
Score:
2
Max. score:
4
Remarks on result:
other: brown staining of the skin by the test substance
Irritation parameter:
edema score
Basis:
animal #2
Time point:
72 h
Score:
1
Max. score:
4
Remarks on result:
other: brown staining of the skin by the test substance; reduced flexibility of the skin
Irritation parameter:
edema score
Basis:
animal #2
Time point:
7 d
Score:
1
Max. score:
4
Remarks on result:
other: brown staining of the skin by the test substance; reduced flexibility; scalliness
Irritation parameter:
edema score
Basis:
animal #2
Time point:
14 d
Score:
0
Max. score:
4
Remarks on result:
other: bald skin
Irritation parameter:
erythema score
Basis:
animal #3
Time point:
other: 1 h
Score:
1
Max. score:
4
Remarks on result:
other: brown staining of the skin by the test substance
Irritation parameter:
erythema score
Basis:
animal #3
Time point:
24 h
Score:
1
Max. score:
4
Remarks on result:
other: brown staining of the skin by the test substance
Irritation parameter:
erythema score
Basis:
animal #3
Time point:
48 h
Score:
1
Max. score:
4
Remarks on result:
other: brown staining of the skin by the test substance
Irritation parameter:
erythema score
Basis:
animal #3
Time point:
72 h
Score:
2
Max. score:
4
Remarks on result:
other: brown staining of the skin by the test substance; reduced flexibility of the skin
Irritation parameter:
erythema score
Basis:
animal #3
Time point:
7 d
Score:
1
Max. score:
4
Remarks on result:
other: brown staining of the skin by the test substance; scaliness
Irritation parameter:
erythema score
Basis:
animal #3
Time point:
14 d
Score:
0
Max. score:
4
Irritation parameter:
edema score
Basis:
animal #3
Time point:
other: 1 h
Score:
2
Max. score:
4
Remarks on result:
other: brown staining of the skin by the test substance
Irritation parameter:
edema score
Basis:
animal #3
Time point:
24 h
Score:
2
Max. score:
4
Remarks on result:
other: brown staining of the skin by the test substance
Irritation parameter:
edema score
Basis:
animal #3
Time point:
48 h
Score:
2
Max. score:
4
Remarks on result:
other: brown staining of the skin by the test substance
Irritation parameter:
edema score
Basis:
animal #3
Time point:
72 h
Score:
2
Max. score:
4
Remarks on result:
other: brown staining of the skin by the test substance; reduced flexibility of the skin
Irritation parameter:
edema score
Basis:
animal #3
Time point:
7 d
Score:
1
Max. score:
4
Remarks on result:
other: brown staining of the skin by the test substance; scaliness
Irritation parameter:
edema score
Basis:
animal #3
Time point:
14 d
Score:
0
Max. score:
4
Remarks on result:
other: scaliness
Irritant / corrosive response data:
Four hours exposure to 0.5 g of A 012 resulted in very slight, well defined or moderate to severe erythema and slight or moderate oedema in the treated skin-areas of the three rabbits. Reduced flexibility and scaliness of the treated skin were noted among all animals between 72 hours and 14 days after treatment. In addition, the treated skin appeared bald in two animals at 7 or 14 days after treatment. The skin irritation had resolved within 14 days after exposure in one animal, but remained present up to termination in the other animals.

There was no evidence of a corrosive effect on the skin.
Other effects:
Colouration / Rernnants
Brown staining of the treated skin by the test substance was observed on all animals during the observation period, which did not hamper the scoring of the skin reactions. No remnants of the test substance were present.

Toxicity/ Mortality
No symptoms of systemic toxicity were observed in the animals during the test period and no mortality occurred.

Applicant's summary and conclusion

Interpretation of results:
irritating
Conclusions:
No evidence of full thickness destruction of the skin or scar tissue was observed during the observation period, indicating that no corrosion of the skin had occurred by dermal application of A 012 to the intact rabbit skin.
Based an these results and according to the:
- OECD Harmonized lntegrated Hazard Classification System for Human Health and Environmental Effects of Chemical Substances (OECD, 1998), A 012 should be classified as: mild skin irritant (Class 3).
- EC criteria for classification arid labelling requirements for dangerous substances and preparations (Council Directive 67/548/EEC), A 012 should be labelled as: irritating to skin (R 38).
Executive summary:

Primary skin irritation/corrosion study with A 012 in the rabbit (4-hour semi­occlusive application). The study was carried out based on the guidelines described in: OECD No.404, "Acute Dermal lrritation/Corrosion" (2002); EC Commission Directive 92/69/EEC, 8.4, "Acute Toxicity - Skin irritation" (1992); US EPA, OPPTS 870.2500, Acute Dermal Irritation (1998) and JMAFF, Japanese Test Guidelines (2000).

Three rabbits were exposed to 0.5 grams of A 012 applied onto clipped skin for 4 hours using a semi-occlusive dressing. Observations were made 1, 24, 48 and 72 hours, and 7 and 14 days after exposure. Exposure to A 012 resulted in very slight, well defined or moderate to severe erythema and slight or moderate oedema in the treated skin-areas of the rabbits. Reduced flexibility and scaliness of the treated skin were noted among all animals between 72 hours and 14 days after treatment. In addition, the treated skin appeared bald in two animals at 7 or 14 days after treatment. The skin irritation had resolved within 14 days after exposure in one animal, but remained present up to termination in the other animals.

Brown staining of the treated skin by the test substance was observed on all animals during the observation period, which did not hamper the scoring of the skin reactions. No evidence of full thickness destruction of the skin or scar tissue was observed during the observation period, indicating that no corrosion of the skin had occurred by dermal application of A 012 to the intact rabbit skin.