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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:
02/08/1991-28/11/1991
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
guideline study
Remarks:
According to the OECD Guideline and in compliance with GLP

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
1991
Report date:
1991

Materials and methods

Test guidelineopen allclose all
Qualifier:
according to guideline
Guideline:
OECD Guideline 404 (Acute Dermal Irritation / Corrosion)
Deviations:
no
Qualifier:
according to guideline
Guideline:
EU Method B.4 (Acute Toxicity: Dermal Irritation / Corrosion)
Deviations:
no
GLP compliance:
yes

Test material

Reference
Name:
Unnamed
Type:
Constituent
Test material form:
liquid
Details on test material:
- Physical state: clear yellow liquid
- Storage conditions: between 20-30°C in the dark
- Stability under test conditions: stable

Test animals

Species:
rabbit
Strain:
New Zealand White
Details on test animals or test system and environmental conditions:
TEST ANIMALS
- Source: Broekman Institute, Someren, The Netherlands
- Age at study initiation: 17 weeks
- Weight at study initiation: 2856-2986 g
- Housing: Individually in labelled cages, with perforated floors and equipped with an automatic drinking system.
- Diet (e.g. ad libitum): Standard laboratory rabbit diet (LKK-20, pellet diameter 4mm, Hope Farms, Woerden, The Netherlands), approx.100 gram per day.
- Water (e.g. ad libitum): free access to tap water diluted with decalcified water.
- Acclimation period: five days


ENVIRONMENTAL CONDITIONS
- Temperature (°C): 21
- Humidity (%): 55
- Air changes (per hr): 15
- Photoperiod (hrs dark / hrs light): 12/12

Test system

Type of coverage:
semiocclusive
Preparation of test site:
shaved
Vehicle:
unchanged (no vehicle)
Controls:
yes, concurrent no treatment
Amount / concentration applied:
TEST MATERIAL
- Amount(s) applied (volume or weight with unit): 0.5 mL
Duration of treatment / exposure:
4 hours
Observation period:
Body weight: Day 1 of test (application day)
Irritation: Days 1, 2, 3, 4, 8, 15 and 22
Number of animals:
3 females
Details on study design:
TEST SITE
- Area of exposure: dorsal/flank area
- Type of wrap if used: test substance was applied to the intact skin using a surgical gauze patch 2 x 3 cm mounted on Micropore tape. The dressing was wrapped around the abdomen and secured with an elastic bandage.

REMOVAL OF TEST SUBSTANCE
- Washing: the remaining test substance was removed using a tissue moistened with tap water and subsequently a dry tissue.
- Time after start of exposure: 4h

OBSERVATION TIME POINTS
(indicate if minutes, hours or days) : approx 1, 24, 48, 72 hours and 7, 14 and 21 days after the removal of the dressings and test substance

SCORING SYSTEM:
Erythema and eschar formation
No erythema: 0
Very slight erythem: 1
Well-defined erythema:2
Moderate to severe erythema: 3
Severe erythema to slight eschar formation: 4

Oedema formation
No oedema:0
Very slight oedema: 1
Slight oedema:2
Moderate oedema:3
Severe oedema:4

Results and discussion

In vivo

Resultsopen allclose all
Irritation parameter:
erythema score
Basis:
animal #1
Time point:
24 h
Score:
2
Reversibility:
not reversible
Irritation parameter:
edema score
Basis:
animal #1
Time point:
24 h
Score:
3
Reversibility:
not reversible
Irritation parameter:
erythema score
Basis:
animal #2
Time point:
24 h
Score:
1
Reversibility:
not reversible
Irritation parameter:
edema score
Basis:
animal #2
Time point:
24 h
Score:
3
Reversibility:
not reversible
Irritation parameter:
erythema score
Basis:
animal #3
Time point:
24 h
Score:
2
Reversibility:
not reversible
Irritation parameter:
edema score
Basis:
animal #3
Time point:
24 h
Score:
3
Reversibility:
not reversible
Irritation parameter:
erythema score
Basis:
animal #1
Time point:
48 h
Score:
4
Reversibility:
not reversible
Irritation parameter:
edema score
Basis:
animal #1
Time point:
48 h
Score:
4
Reversibility:
not reversible
Irritation parameter:
erythema score
Basis:
animal #2
Time point:
48 h
Score:
3
Reversibility:
not reversible
Irritation parameter:
edema score
Basis:
animal #2
Time point:
48 h
Score:
4
Reversibility:
not reversible
Irritation parameter:
erythema score
Basis:
animal #3
Time point:
48 h
Score:
4
Reversibility:
not reversible
Irritation parameter:
erythema score
Basis:
animal #1
Time point:
72 h
Score:
4
Reversibility:
not reversible
Irritation parameter:
edema score
Basis:
animal #1
Time point:
72 h
Score:
4
Reversibility:
not reversible
Irritation parameter:
erythema score
Basis:
animal #2
Time point:
72 h
Score:
4
Reversibility:
not reversible
Irritation parameter:
edema score
Basis:
animal #2
Time point:
72 h
Score:
4
Reversibility:
not reversible
Irritation parameter:
erythema score
Basis:
animal #3
Time point:
72 h
Score:
4
Reversibility:
not reversible
Irritation parameter:
edema score
Basis:
animal #3
Time point:
72 h
Score:
4
Reversibility:
not reversible
Irritant / corrosive response data:
The observed skin irritation consisted of slight eschar formation, fissuring of the skin and severe oedema in all three animals. The skin irritation had not resolved completely within the study period (22 days) in all three animals.
Very slight erythema and very slight oedema were observed in animals No. 689 and 711 and very slight erythema only was observed in animal No. 710 on day 22.
There was no evidence of a corrosive effect on the skin.
Other effects:
No symptoms of systemic toxicity were observed in the animals during the test period and no mortality occured.

Any other information on results incl. tables

Individual findings:

time after exposure Rabbit No. Erythema Oedema Comments
45 min 689 2 2 -
710 2 1 -
711 2 2 -
24h 689 2 3 -
710 1 3 -
711 2 3 -
48h 689 4 4 The treated skin showed less elasticity.
710 3 4 -
711 4 4 -
72h 689 4 4 Treated area showed fissuring of the skin and slight eschar formation.
710 4 4 Treated area showed fissuring of the skin and slight eschar formation.
711 4 4 The treated skin showed less elasticity.
7 days 689 1 1 The treated area showed new skin formation and was covered with scales.
710 4 3 Treated area showed fissuring of the skin and slight eschar formation. The treated skin also showed less elasticity.
711 4 3 Treated area showed fissuring of the skin and slight eschar formation.
14 days 689 1 1 The treated area showed new skin formation and was covered with scales.
710 1 1 Approx. 75% of the treated area showed new skin formation and approx. 25% showed scaliness.
711 1 1 Approx. 75% of the treated area showed new skin formation and approx. 25% showed scaliness.
21 days 689 1 1 -
710 1 0 -
711 1 1 -

Note: The observed skin irritation was noted on a skin area covering approximately 6 x 4 cm, due to spreading of the test substace during exposure.

Calculations for EEC Classification:

Rabbit No. 689 Rabbit No. 710 Rabbit No. 711
observation time Erythema Oedema Erythema Oedema Erythema Oedema
24 h 2 3 1 3 2 3
48 h 4 4 3 4 4 4
72 h 4 4 4 4 4 4
mean value 3.3 3.7 2.7 3.7 3.3 3.7

Applicant's summary and conclusion

Interpretation of results:
Category 2 (irritant) based on GHS criteria
Conclusions:
Under the test conditions, test material is classified as H315 "Causes Skin Irritation" Category 2 according to the Regulation (EC) No. 1272/2008 (CLP) and to the GHS.
Executive summary:

In a dermal irritation study performed according to the OECD Guideline No. 404, and in compliance with GLP, 0.5 mL of test material was applied on the clipped skin of the dorsal flank area of 3 female New Zealand rabbits. Test sites were covered with a semi-occlusive dressing for 4 hours, followed by seven observations at approximately 1, 24, 48 and 72 hours and 7, 14 and 21 days after removal of dressings and remaining test substance.

The observed skin irritation consisted of slight eschar formation, fissuring of the skin and severe oedema in all three animals. The skin irritation had not resolved completely within the study period (22 days) in all three animals.

Very slight erythema and very slight oedema were observed in animals No. 689 and 711 and very slight erythema only was observed in animal No. 710 on day 22.

There was no evidence of a corrosive effect on the skin.

The individual mean scores for each animal within 3 scoring times (24, 48 and 72 h) were 3.3 / 2.7 / 3.3 for erythema and 3.7 / 3.7 / 3.7 for oedema.

Under the test conditions, test material is classified as H315 "Causes Skin Irritation" Category 2 according to the Regulation (EC) No. 1272/2008 (CLP) and to the GHS.

This study is considered as acceptable and satisfies the requirement for skin irritation endpoint.