Reaction mass of endo-2-methyl-exo-3-methyl-exo-2-[(endo-3-methylbicyclo[2.2.1]hept-endo-2-yl)methyl]bicyclo[2.2.1]heptane and endo-2-methyl-exo-3-methyl-exo-2-[(endo-2-methylbicyclo[2.2.1]hept-endo-3-yl)methyl]bicyclo[2.2.1]heptane and endo-2-methyl-exo-3-methyl-exo-2-[(exo-3-methylbicyclo[2.2.1]hept-exo-2-yl)methyl]bicyclo[2.2.1]heptane and endo-2-methyl-exo-3-methyl-exo-2-[(exo-2-methylbicyclo[2.2.1]hept-exo-3-yl)methyl]bicyclo[2.2.1]heptane

Skin irritation / corrosion

Administrative data

Endpoint:

skin irritation: in vivo

Type of information:

experimental study

Adequacy of study:

key study

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

other: Study conducted under GLP in accordance with an internationally recognised guideline

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

2005

Report date:

2005

Materials and methods

Test guideline

Test guideline 1

Qualifier:

according to guideline

Guideline:

OECD Guideline 404 (Acute Dermal Irritation / Corrosion)

Test guideline 2

Qualifier:

according to guideline

Guideline:

EU Method B.4 (Acute Toxicity: Dermal Irritation / Corrosion)

Test guideline 3

Qualifier:

according to guideline

Guideline:

EPA OPPTS 870.2500 (Acute Dermal Irritation)

GLP compliance:

yes (incl. QA statement)

Test material

Test material information

Constituent 1

Reference substance name:

T-13

IUPAC Name:

T-13

Test material form:

other: liquid

Details on test material:

- Analytical purity: 88%
- Lot/batch No.: 030522 (olefin content <0.1%%)
- Appearance: clear colourless liquid
- Expiration date of the lot/batch: 25 November 2005
- Storage conditions: 4°C in the dark

Test animals

Species:

rabbit

Strain:

New Zealand White

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Source:
- Age at study initiation: at least 12 weeks
- Weight at study initiation: 3.35 to 3.59
- Housing: housed individually in stainless steel cages with perforated floors
- Diet (e.g. ad libitum): 125 g standard laboratory rabbit diet available each day
- Water: ad libitum, drinking water
- Acclimation period: yes, duration not reported

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 16 to 20°C
- Humidity (%): 40 to 70%
- Air changes (per hr): not reported
- Photoperiod (hrs dark / hrs light): 12 hrs light / 12 hrs dark

IN-LIFE DATES: From: To: 9 February to 16 March 2005

Test system

Type of coverage:

semiocclusive

Preparation of test site:

clipped

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
- Concentration: 100%

Duration of treatment / exposure:

4 hours

Observation period:

15 days

Number of animals:

2

Details on study design:

TEST SITE
- Area of exposure: from the dorsolumbar region of each rabbit exposing an appropriate sized area of skin.
- % coverage: not reported
- Type of wrap if used: for exposures of one hour or more each treatment site was covered with cotton wool and elasticated bandage dressing for the duration of the exposure period.

REMOVAL OF TEST SUBSTANCE
- Washing: At the end of the exposure period the semi-occlusive dressing and gauze pad were removed and the treatment site was washed with lukewarm water (30-40°C) to remove any residual test substance. The treated area was blotted dry with absorbent paper.
- Time after start of exposure: a single animal received three exposures (of three minutes, one or four hours duration) in a step-wise manner and acted as a preliminary screen. In the absence of a severe effect on removal of the dressings the next exposure was initiated.

SCORING SYSTEM:

Erythema and Eschar Formation
No erythema ...............................................................................................................................................0
Very slight erythema (barely perceptible) ......................................................................................................1
Well defined erythema ..................................................................................................................................2
Moderate to severe erythema .......................................................................................................................3
Severe erythema (beef redness) to eschar formation (injuries in depth) preventing grading of erythema.............4
Maximum possible: 4

Oedema Formation
No oedema....................................................................................................................................................0
Very slight oedema (barely perceptible) .........................................................................................................1
Slight oedema (edges of area well defined by definite raising) ..........................................................................2
Moderate oedema (raised approximately 1 mm) .............................................................................................3
Severe oedema (raised more than 1 mm and extending beyond area of exposure) ...........................................4
Maximum possible: 4

Results and discussion

In vivo

Results

Results 1

Irritation parameter:

erythema score

Remarks:

4h exposure

Basis:

animal #1

Time point:

24/48/72 h

Score:

3

Max. score:

3

Reversibility:

fully reversible within: 15 days

Remarks on result:

positive indication of irritation

Results 2

Irritation parameter:

erythema score

Remarks:

4h exposure

Basis:

animal #2

Time point:

24/48/72 h

Score:

2

Max. score:

2

Reversibility:

fully reversible within: 15 days

Remarks on result:

positive indication of irritation

Results 3

Irritation parameter:

erythema score

Basis:

animal #3

Remarks:

3rd animal not required

Time point:

24/48/72 h

Score:

0

Max. score:

0

Reversibility:

other: not applicable

Remarks on result:

other: not applicable - 3rd animal not required

Results 4

Irritation parameter:

edema score

Remarks:

4h exposure

Basis:

animal #1

Time point:

24/48/72 h

Score:

2

Max. score:

2

Reversibility:

fully reversible within: 15 days

Remarks on result:

probability of moderate irritation

Results 5

Irritation parameter:

edema score

Remarks:

4h exposure

Basis:

animal #2

Time point:

24/48/72 h

Score:

1

Max. score:

1

Reversibility:

fully reversible within: 8 days

Remarks on result:

probability of weak irritation

Results 6

Irritation parameter:

edema score

Basis:

animal #3

Remarks:

3rd animal not required

Time point:

24/48/72 h

Score:

0

Max. score:

0

Reversibility:

other: not applicable

Remarks on result:

other: 3rd animal not required

Irritant / corrosive response data:

Positive indication of irritation based on erythema mean score of 2.5 for 2 animals

Any other information on results incl. tables

3 -minute exposure

Well-defined erythema with or without very slight or slight oedema was apparent during the first four days after removal of the dressings. On Day 6 and 8 very slight erythema and exfoliation were evident; exfoliation alone was apparent on Day 15.

The Primary Irritation Index after 3 minute exposure was calculated to be 3.0; the mean score for the assessment 24, 48 and 72 hours after bandage removal reached the EC classification threshold. Accordingly, a 3 minute exposure of T-13 gave rise to a 'moderate irritant' response which would, if seen in two or more animals, warrant labelling with R38 "Irritating to skin" risk phrase.

1 -hour exposure

Very-slight or well-defined erythema with or without very slight oedema was evident throughout the first week after bandage removal; from 24 hours after bandage removal resolving during the second week the reaction was noted to have spread beyond the application site and from Day 6 exfoliation was apparent. Exfoliation alone was evident on Day 15.

The Primary Irritation Index after 1 hour exposure was calculated to be 3.0; the mean score for the assessment 24, 48 and 72 hours after bandage removal reached the EC classification threshold. Accordingly, a l hour exposure of T-13 gave rise to a 'moderate irritant' response which would, if seen in two or more animals, warrant labelling with R38 "Irritating to skin" risk phrase.

Four hour exposure

Well-defined or moderate to severe erythema with or without very slight or slight oedema was apparent throughout the first week after bandage removal; a clear staining on the periphery of the test site was evident during this time. One animal additionally showed blanching of the test site during the first four days of observations, loss of flexibility on Days 6 and 8, sensitivity to touch 24 hours after bandage removal and the reactions spread beyond the application site. Exfoliation was apparent in both animals during the last week of the observation period.

Applicant's summary and conclusion

Interpretation of results:

other: Irritating according to CLP classification criteria

Conclusions:

According to CLP classification criteria, irritation Cat 2 applies when erythema or odema scores are >=2.3 - <=4.0 in two out of three animals. In this study a conclusion on classification for irritation could be made with the use of only 2 animals (erythema score 3 in one animal and erythema score 2 in the other animal). On this basis the substance is classified as irritant Cat 2.