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Description of key information

Skin irritation (OECD 404, RL1): (female rabbit) The test material revealed a long lasting irritation potential with a remarkable damage of the skin, the test material should be regarded as a corrosive Category 1.

Key value for chemical safety assessment

Skin irritation / corrosion

Link to relevant study records

Referenceopen allclose all

Endpoint:
skin irritation: in vivo
Type of information:
experimental study
Adequacy of study:
key study
Study period:
17.11.-08.12.2005
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
guideline study
Qualifier:
according to guideline
Guideline:
OECD Guideline 404 (Acute Dermal Irritation / Corrosion)
Version / remarks:
2002
Deviations:
no
Qualifier:
according to guideline
Guideline:
EU Method B.4 (Acute Toxicity: Dermal Irritation / Corrosion)
Version / remarks:
92/69/EEC
Deviations:
no
GLP compliance:
yes
Species:
rabbit
Strain:
New Zealand White
Details on test animals or test system and environmental conditions:
TEST ANIMALS
- Source: Charles River Wiga GmbH, Kißlegg
- Age at study initiation: about 22 weeks
- Weight at study initiation: 4.29 kg
- Housing: separately in special rabbit cage (manufacturer: Becker; type K99130 KU, floor area about 5400 cm2, a shelter with an integrated sitting board of about 1820 cm2; overall height: 60 cm)
- Diet (e.g. ad libitum): ad libitum
- Water (e.g. ad libitum): ad libitum
- Acclimation period: more than 7 days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 15 to 16 °C
- Air changes (per hr): --
- Photoperiod (hrs dark / hrs light): 12/12 hours

IN-LIFE DATES: From: day 1 To: day 22
Type of coverage:
semiocclusive
Preparation of test site:
shaved
Vehicle:
unchanged (no vehicle)
Controls:
not required
Amount / concentration applied:
0.5 mL


Duration of treatment / exposure:
4 h
Observation period:
The first examination of the treated skin sites followed 1 hour after removal of the patch. Thereafter, examinations were performed daily for further 21 days.
Number of animals:
1
Details on study design:
TEST SITE
- Area of exposure: 6 cm2
- % coverage: 100
- Type of wrap if used: self-adhesive fabric

REMOVAL OF TEST SUBSTANCE
- Washing (if done): yes
- Time after start of exposure: 4 h

OBSERVATION TIME POINTS
(indicate if minutes, hours or days): 1 hour after removal of the patches, and then daily for a period of further 21 days


SCORING SYSTEM:
Skin changes at the application sites were evaluated according to the DRAIZE-, OECD-and EEC recommendations.
Irritation parameter:
erythema score
Basis:
animal #1
Remarks:
(mean score 1)
Time point:
24/48/72 h
Score:
2.67
Max. score:
4
Reversibility:
not fully reversible within: 22 days
Irritation parameter:
edema score
Basis:
animal #1
Remarks:
(mean score 1)
Time point:
24/48/72 h
Score:
2.67
Max. score:
4
Reversibility:
fully reversible within: 96 h
Irritant / corrosive response data:
Reversibility of any observed effect: Changes not fully reversible within 22 days

Only 1 rabbit was used for the study. No signs of pain were observed after administration. Under the conditions of the present study erythema (scores 2 to 4) were observed from experimental day 1 up to the end of the study and oedema (score 4) from day 1 up to 3 of the experimental part. Furthermore scrabs, hardened brittle skin, peeling off skin, epithelization, and scales from experimental day 4 up to the end of the experimental part (day 22) were seen.

Day
(after treatment)
1
(1h)
2
(24 h)
3
(48h)
4
(72 h)
Erythema 2 2 2 4
Edema 4 4 4 0

No signs of clinical toxicity were detected.

Body weight development of the treated rabbit was inconspicuous.

Interpretation of results:
Category 1 (corrosive) based on GHS criteria
Conclusions:
The test material revealed a long lasting irritation potential with a remarkable damage of the skin.
According to the EEC-Directive 1272/2008 the test material should be regarded as a corrosive Category 1.
Executive summary:

Purpose

The purpose of this assay was to identify the skin irritation/corrosion potential of the test material  when applied to the intact skin of previously shaven rabbits for a 4 hours period under semiocclusive conditions. This study should provide a rational basis for risk assessment to the irritating potential of the test item in man.

Study Design

To test for primary skin irritation, 0.5 mL of the test material was spread onto 6 cm2patches and applied to the intact skin of previously shaven rabbits for a 4 hours period under semiocclusive conditions. The study was an initial test with one animal. This animal showed signs of irritation (well defined erythema, edema, hardened brittle skin, scabs, epithelization, and scales) and no more animals were treated. The first examination of the treated skin sites followed 1 hour after removal of the patch. Thereafter, examinations were performed daily for further 21 days.

Results

Only one rabbit was used for the study. No signs of pain were observed after administration. Under the conditions of the present study erythema (scores 2 to 4) were observed from experimental day 1 up to the end of the study and edema (score 4) from day 1 up to 3 of the experimental part. Furthermore scabs, hardened brittle skin, peeling off skin, epithelization, and scales from experimental day 4 up to the end of the experimental part were seen.

Individual values of one rabbit

Day
(after treatment)
1
(1h)
2
(24 h)
3
(48h)
4
(72 h)
Erythema 2 2 2 4
Edema 4 4 4 0



Evaluation of each animal:

Animal No Mean score
(24, 48, 72 h)
Maximum value
(24, 48, 72 h)
1
1
Erythema 2.67 4
Edema 2.67 4

Conclusion

The test material revealed a long lasting irritation potential with a remarkable damage of the skin.
According to the EEC-Directive 1272/2008 the test material should be regarded as a corrosive Category 1.


Endpoint:
skin irritation: in vitro / ex vivo
Data waiving:
study technically not feasible
Justification for data waiving:
an in vitro skin irritation study does not need to be conducted because adequate data from an in vivo skin irritation study are available
Endpoint conclusion
Endpoint conclusion:
adverse effect observed (corrosive)

Eye irritation

Link to relevant study records
Reference
Endpoint:
eye irritation: in vitro / ex vivo
Data waiving:
study scientifically not necessary / other information available
Justification for data waiving:
the study does not need to be conducted because the substance is classified as skin corrosion, leading to classification as serious eye damage (Category 1)
Endpoint conclusion
Endpoint conclusion:
adverse effect observed (irreversible damage)

Respiratory irritation

Endpoint conclusion
Endpoint conclusion:
adverse effect observed (irritating)

Additional information

In vivo skin irritation study

To test for primary skin irritation, 0.5 mL of the test material was spread onto 6 cm2 patches and applied to the intact skin of previously shaven rabbits for a 4 hours period under semiocclusive conditions. The study was an initial test with one animal. This animal showed signs of irritation (well defined erythema, edema, hardened brittle skin, scabs, epithelization, and scales) and no more animals were treated. The first examination of the treated skin sites followed 1 hour after removal of the patch. Thereafter, examinations were performed daily for further 21 days. The test material revealed a long lasting irritation potential with a remarkable damage of the skin, the test material should be regarded as a corrosive Category 1.

Eye irritation/corrosion

No data on eye irritation/corrosion is available, however, the test item is considered to induce serious eye damage because the test item cause also irreversible damage to the skin.

Respiratory tract irritation

There are currently no validated tests on respiratory tract irritation, however, it is a reasonable precaution to assume that corrosive (and severely irritating) substances would also cause respiratory tract irritation. Since the substance induced serious eye damage, it is assumed as a precautionary measure that the test item cause also respiratory tract irritation.

Justification for classification or non-classification

Based on the reults, the test item is classified for skin irritation category 1 (H314), for eye corrosion category 1 (H318), and STOT SE category 3 (H335) according to Regulation (EC) No 1272/2008.