Registration Dossier

Administrative data

Description of key information

SKIN IRRITATION/CORROSION
(R)-2,2,3-trimethylcyclopen-3-ene-1-acetaldehyde was determined to be a skin irritant according to study performed in line with OECD Guideline 404.

Key value for chemical safety assessment

Skin irritation / corrosion

Link to relevant study records
Reference
Endpoint:
skin irritation: in vivo
Type of information:
experimental study
Adequacy of study:
key study
Study period:
11 May 1998 to 25 May 1998
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
other: A GLP compliant study conducted in compliance with agreed protocols, with no or minor deviations from standard test guidelines and/or minor methodological deficiencies, which do not affect the quality of the relevant results.
Qualifier:
according to guideline
Guideline:
OECD Guideline 404 (Acute Dermal Irritation / Corrosion)
Deviations:
no
GLP compliance:
yes
Species:
rabbit
Strain:
New Zealand White
Details on test animals or test system and environmental conditions:
TEST ANIMALS
- Source: JEGARD, 22120 Yffniac, France
- Weight at study initiation: average weight 2.8 kg
- Diet : complete pelleted rabbit maintenance diet ERGILAP Anco, COFNA (37000 Tours, France)
- Housing: Individual housing on floor grid
- Acclimation period: at least 5 days

ENVIRONMENTAL CONDITIONS
- in accordance with the requirements of 86/609/EEC guideline
Type of coverage:
semiocclusive
Preparation of test site:
shaved
Vehicle:
not specified
Controls:
no
Amount / concentration applied:
TEST MATERIAL
- Amount(s) applied (volume or weight with unit): 0.5 mL/rabbit
Duration of treatment / exposure:
4 hours
Observation period:
14 days after patch removal
Number of animals:
Three - two males and one female
Details on study design:
TEST SITE
- Area of exposure: 2.5 x 2.5 cm gauze held in place with 5 x 5 cm 'Micropore' fastening tape.
- Type of wrap if used: 10 cm wide stretch tape fastened around the trunk by adhesive tape of the same width.

REMOVAL OF TEST SUBSTANCE
- Washing (if done): residual test substance was removed using cotton wool moistened with distilled water.
- Time after start of exposure: 4 hours

SCORING SYSTEM:
The skin was observed at 1, 24, 48 and 72 hours and extended no more than 14 days to establish reversibility. Any irritation was scored using the numerical scale below:

Erythema and eschar formation
No erythema 0
Very slight erythema 1
Well defined erythema 2
Moderate to severe erythema 3
Severe erythema 4

Oedema formation
No oedema 0
Very slight oedema 1
Slight oedema 2
Moderate oedema 3
Severe oedema 4
Irritation parameter:
erythema score
Basis:
mean
Time point:
other: 24 h
Score:
2
Max. score:
4
Irritation parameter:
erythema score
Basis:
mean
Time point:
other: 48 h
Score:
2
Max. score:
4
Irritation parameter:
erythema score
Basis:
mean
Time point:
other: 72 h
Score:
1.7
Max. score:
4
Reversibility:
fully reversible within: day eight for two animals; very slight erythema seen in one animal at the end of the observation period
Irritation parameter:
edema score
Basis:
mean
Time point:
other: 24 h
Score:
3
Max. score:
4
Irritation parameter:
edema score
Basis:
mean
Time point:
other: 48 h
Score:
2.3
Max. score:
4
Irritation parameter:
edema score
Basis:
mean
Time point:
other: 72 h
Score:
2
Max. score:
4
Reversibility:
fully reversible within: day eight for two animals; very slight erythema seen in one animal at the end of the observation period
Irritation parameter:
erythema score
Basis:
animal #1
Time point:
other: 24, 48 and 72 hours
Score:
2
Max. score:
4
Irritation parameter:
erythema score
Basis:
animal #2
Time point:
other: 24, 48 and 72 hours
Score:
2
Max. score:
4
Irritation parameter:
erythema score
Basis:
animal #3
Time point:
other: 24, 48 and 72 hours
Score:
1.7
Max. score:
4
Irritation parameter:
edema score
Basis:
animal #1
Time point:
other: 24, 48 and 72 hours
Score:
3
Max. score:
4
Irritation parameter:
edema score
Basis:
animal #3
Time point:
other: 24, 48 and 72 hours
Score:
2.3
Max. score:
4
Irritation parameter:
edema score
Basis:
animal #3
Time point:
other: 24, 48 and 72 hours
Score:
2
Max. score:
4
Reversibility:
fully reversible within: 6 days
Irritant / corrosive response data:
One hour after patch removal, very slight to well defined erythema (scores 1 and 2) and moderate to severe oedema (scores 3 and 4) were seen in all animals. During the following 72 hours of the test, erythema reactions increased in two animals but decreased in one and oedema reactions decreased in all animals.

The reversibility of these reactions was complete for two animals 6 and 8 days after treatment. The remaining animal still had very slight erythema at the end of the observation period.
Other effects:
Structural modifications were observed between days 2 and 3; a cutaneous thickening associated with a dryness of the skin in all animals and a slight loss of skin in one animal.

Table 1: Individual values of skin reactions

   Scores           Mean scores  Scores   
 Animal number  1 hour (D1)  24 hours  48 hours  72 hours  over 24-72h  D5  D6
 Erythema                     
 7255  1  2  2  2  2.0  2  2
 7270  1  2  2  2  2.0  2  1
 7278  2  2  2  1  1.7  1  1
 Oedema                     
 7255  4  3  3  3  3.0  2  2
 7270  3  3  2  2  2.3  2  2
 7278  3  3  2  1  2.0  1  0
Interpretation of results:
irritating
Remarks:
Migrated information Criteria used for interpretation of results: EU
Conclusions:
Under the conditions of the test, the test substance was determined to be a skin irritant.
Executive summary:

In a GLP compliant skin irritation study conducted in line with standardised guideline OECD 404, the skin irritancy of the test substance was determined. Under the conditions of the test, following application of the test substance for four hours under a semi-occlusive patch, very slight to well defined erythema and moderate to severe oedema was seen in all animals. During the following 72 hours, erythema reactions increased in two animals but decreased in one and oedema reactions decreased in all animals. The reversibility of these reactions was complete for two animals 6 and 8 days after treatment and the remaining animal still had very slight erythema at the end of the observation period. The test substance is considered to be a skin irritant.

Endpoint conclusion
Endpoint conclusion:
adverse effect observed (irritating)

Eye irritation

Endpoint conclusion
Endpoint conclusion:
no study available

Respiratory irritation

Endpoint conclusion
Endpoint conclusion:
no study available

Additional information

Skin

Two GLP compliant studies were performed, one each in accordance with standardised guidelines OECD 404 and EU Method B.4, both with a sufficient level of detail to assess the quality of the presented data. The studies were performed to a good standard and were assigned a reliability score of 1 using the principle for assessing data quality as set out in Klimisch (1997). The key study is the most recently performed study and was slightly better presented. This study concluded that the substance was a skin irritant whereas the supporting study concluded that the substance was not. However, the erythema classification score for the supporting study almost met the criteria for classifying the substance as a skin irritant and so it is considered that the substance should be classified as such.


Justification for selection of skin irritation / corrosion endpoint:
Two GLP studies performed in accordance with standardised guidelines are available. The key study was the most recently performed and slightly better presented.

Effects on skin irritation/corrosion: irritating

Justification for classification or non-classification

Skin

In line with Directive 67/548/EEC and Regulation 1272/2008, the test substance is considered to be classified as a skin irritant. Under Directive 67/548/EEC the substance has been classified as Xi (Irritant) and R38 (Irritating to skin). Under Regulation 1272/2008, the substance has been classified as Skin Irrit. 2 and H315 (Causes skin irritation).

Eye

The substance is classified as an eye irritant at the EU level with a classification of Xi (Irritant) and R36 (Irritating to eyes) under Directive 67/548/EEC and an equivalent classification of Eye Irrit. 2 and H319 (Causes serious eye irritation). It is not clear as to why this classification has been given, but as there is no available data for this endpoint, no change to the classification is proposed.