Reaction mass of (+-)-(1RS,2SR,5SR,7RS,8SR)-5-METHYLTRICYCLO[6.2.1.02,7]UNDECAN-4-ONE and (+-)-(1RS,2SR,5RS,7RS,8SR)-5-METHYLTRICYCLO[6.2.1.02,7]UNDECAN-4-ONE

Endpoint summary

Description of key information

Skin irritation: Not irritating (Draize test, Rel.2, K).
Eye irritation: Not irritating (Draize test, Rel. 2, K).

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:

No data

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

other: see 'Remark'

Remarks:

Study performed according to the Draize procedure. Worst-case conditions were used (24 h occlusive exposure) and observation were performed at 24 and 72h only. However only slight effects were observed after 24 hours, and were completely reversible within 72 hours. A repeat study is unlikely to show worse effects, therefore this study was considered sufficiently robust to cover this endpoint.

Reason / purpose for cross-reference:

reference to same study

Reason / purpose for cross-reference:

reference to other study

Qualifier:

no guideline followed

Principles of method if other than guideline:

Study was performed according to Draize procedure (Draize, 1944).

GLP compliance:

no

Remarks:

(pre-GLP)

Species:

rabbit

Strain:

New Zealand White

Details on test animals or test system and environmental conditions:

None

Type of coverage:

occlusive

Preparation of test site:

clipped

Vehicle:

unchanged (no vehicle)

Controls:

not required

Amount / concentration applied:

TEST MATERIAL
- Amount(s) applied (volume or weight with unit): 0.5 mL (0.5 g)

Duration of treatment / exposure:

24 h

Observation period:

24 and 72 h

Number of animals:

6

Details on study design:

TEST SITE
- Area of exposure: No data
- % coverage: No data
- Type of wrap if used: After test material application, entire trunk of each animal was covered with an impermeable occlusive wrapping.

REMOVAL OF TEST SUBSTANCE
- Washing (if done): No
- Time after start of exposure: Test material was removed 24 h following application.

SCORING SYSTEM: According to Draize method (1944).

Irritation parameter:

erythema score

Basis:

mean

Remarks:

(6 animals)

Time point:

other: Mean 24 and 72 h

Score:

0.5

Max. score:

4

Reversibility:

fully reversible within: 72 h

Remarks on result:

other: Intact skin

Irritation parameter:

edema score

Basis:

mean

Remarks:

(6 animals)

Time point:

other: Mean 24 and 72 h

Score:

0

Max. score:

4

Remarks on result:

other: Intact skin

Irritant / corrosive response data:

- Very slight erythema observed in all animals which was reversible within 72 h.

Other effects:

No data

Table 7.3.1/1: Mean skin irritant/corrosive response data for 6 animals at each observation time

Score at time point / Reversibility	Intact skin		Abraded skin
	Erythema Max. score 4	Oedema Max. score 4	Erythema Max. score 4	Oedema Max. score 4
24 h	1/1/1/1/1/1	0/0/0/0/0/0	1/1/1/1/1/1	0/0/0/0/0/0
72 h	0/0/0/0/0/0	0/0/0/0/0/0	0/0/0/0/0/0	0/0/0/0/0/0
Average 24 and 72 h for 6 animals	0.5	0	0.5	0

Interpretation of results:

not irritating

Remarks:

Migrated information Criteria used for interpretation of results: EU

Conclusions:

Under the test conditions, the test material induced very slight erythema which was reversible within 72 h. Therefore the test material is not classified as irritant to the skin.

Executive summary:

In a dermal irritation study performed following the Draize procedure, 0.5 mL (0.5 g) of undiluted test material was dermally applied on the clipped areas of intact and abraded skin of 6 New Zealand White rabbits. Test sites were covered with an occlusive dressing for 24 h. Skin irritation was assessed and scored according to the Draize scale at 24 and 72 h after the removal of the patch.

The test material induced very slight erythema which was reversible within 72 h. The mean scores calculated for all animals within 2 scoring times (24 and 72 hours) were 0.5 for erythema and 0.0 for oedema.

Therefore the test material is not classified as irritant to the skin according to the annex VI of the Regulation EC No. 1272/2008 (CLP).

Although some details on experimental conditions were missing, this study is considered as acceptable and satisfies the requirement for skin irritation endpoint.

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed (not irritating)

Eye irritation

Link to relevant study records

Reference

Endpoint:

eye irritation: in vivo

Type of information:

experimental study

Adequacy of study:

key study

Study period:

From October 02 to December 14, 1978

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

other: Study performed according to the Draize procedure which is similar to the current OECD Test Guideline No. 405.

Reason / purpose for cross-reference:

reference to same study

Reason / purpose for cross-reference:

reference to other study

Qualifier:

no guideline followed

Principles of method if other than guideline:

Study was performed according to modified Draize procedure (Draize, 1944).

GLP compliance:

no

Remarks:

(pre-GLP)

Species:

rabbit

Strain:

New Zealand White

Details on test animals or tissues and environmental conditions:

TEST ANIMALS
- Source: Summit View Farm, Belvidere, New Jersey, USA
- Weight at study initiation: 1.8-2.4 kg
- Diet: Wayne animal feed, ad libitum
- Water: Water, ad libitum

Vehicle:

unchanged (no vehicle)

Controls:

other: untreated eye served as control

Amount / concentration applied:

TEST MATERIAL
- Amount(s) applied (volume or weight with unit): 0.1 mL

Duration of treatment / exposure:

The treated eyes of all animals remained unwashed for 24 h.

Observation period (in vivo):

Days 1, 2 and 3 following instillation of the test material.

Number of animals or in vitro replicates:

6

Details on study design:

REMOVAL OF TEST SUBSTANCE
- Washing (if done): No

SCORING SYSTEM: According to Draize scale.

TOOL USED TO ASSESS SCORE: Readings were facilitated by hand-held lenses.

Irritation parameter:

cornea opacity score

Basis:

mean

Remarks:

(6 animals)

Time point:

other: Mean 24, 48 and 72 h

Score:

0

Max. score:

4

Irritation parameter:

iris score

Basis:

mean

Remarks:

(6 animals)

Time point:

other: Mean 24, 48 and 72 h

Score:

0.06

Max. score:

2

Reversibility:

fully reversible within: 2 days

Irritation parameter:

conjunctivae score

Basis:

mean

Remarks:

(6 animals)

Time point:

other: Mean 24, 48 and 72 h

Score:

0.28

Max. score:

3

Reversibility:

fully reversible within: 2 days

Irritation parameter:

chemosis score

Basis:

mean

Remarks:

(6 animals)

Time point:

other: Mean 24, 48 and 72 h

Score:

0.17

Max. score:

4

Reversibility:

fully reversible within: 2 days

Irritant / corrosive response data:

- Animals showed weak conjunctival reactions (redness and chemosis) which were reversible within 2 days.
- One animal showed iris reaction of grade 1 which was reversible within 2 days.

Other effects:

None

Table 7.3.2/1: Mean eye irritation response data of 6 animals at each observation time

Score at time point / Reversibility	Cornea		Iris (/2)	Conjunctivae
	Opacity (/4)	Area (/4)		Redness (/3)	Chemosis (/4)	Discharge (/3)
Day 1 (24 h)	0	0	0.17	0.83	0.5	0.17
Day 2 (48 h)	0	0	0	0	0	0
Day 3 (72 h)	0	0	0	0	0	0
Mean	0	0	0.06	0.28	0.17	0.06
Reversibility	-	-	-	Completely reversible	Completely reversible	Completely reversible
Average time for reversion	-	-	-	2 days	2 days	2 days

Table 7.3.2/2: Eye irritation response data for each animal at each observation time

Score at time point	Cornea		Iris (/2)	Conjunctivae
	Opacity (/4)	Area (/4)		Redness (/3)	Chemosis (/4)	Discharge (/3)
Day 1 (24 h)	0 / 0 / 0 / 0 / 0 / 0	0 / 0 / 0 / 0 / 0 / 0	0 / 0 / 0 / 1 / 0 / 0	1 / 1 / 1 / 1 / 1 / 0	1 / 1 / 0 / 1 / 0 / 0	0 / 0 / 0 / 1 / 0 / 0
Day 2 (48 h)	0 / 0 / 0 / 0 / 0 / 0	0 / 0 / 0 / 0 / 0 / 0	0 / 0 / 0 / 0 / 0 / 0	0 / 0 / 0 / 0 / 0 / 0	0 / 0 / 0 / 0 / 0 / 0	0 / 0 / 0 / 0 / 0 / 0
Day 3 (72 h)	0 / 0 / 0 / 0 / 0 / 0	0 / 0 / 0 / 0 / 0 / 0	0 / 0 / 0 / 0 / 0 / 0	0 / 0 / 0 / 0 / 0 / 0	0 / 0 / 0 / 0 / 0 / 0	0 / 0 / 0 / 0 / 0 / 0
Average 24, 48 and 72 h	0 / 0 / 0 / 0 / 0 / 0	0 / 0 / 0 / 0 / 0 / 0	0 / 0 / 0 / 0.33 / 0 / 0	0.33 / 0.33 / 0.33 / 0.33 / 0.33 / 0	0.33 / 0.33 / 0 / 0.33 / 0 / 0	0 / 0 / 0 / 0.33 / 0 / 0
Reversibility	-	-	Completely reversible	Completely reversible	Completely reversible	Completely reversible
Average time (unit) for reversion	-	-	2 days	2 days	2 days	2 days

Interpretation of results:

not irritating

Remarks:

Migrated information Criteria used for interpretation of results: EU

Conclusions:

Under the test conditions, the test material is not classified as irritating to the eyes according to the annex VI of the Regulation EC No. 1272/2008 (CLP).

Executive summary:

In an eye irritation study performed according to the Draize procedure which is similar to the current OECD Test Guideline No. 405, 0.1 mL of undiluted test material was instilled into the right eye of 6 New Zealand White rabbits while the left eye remained untreated and served as control. The treated eyes of all animals remained unwashed for 24 h. Animals were observed at 24, 48 and 72 after instillation of test material into eyes. The reactions in the conjunctivae (redness, chemosis and discharge), the iris and the cornea (opacity and area involved) were scored according to the Draize Scale.

The calculated mean score for all animals within 3 scoring times (24, 48 and 72 h) were 0.28 for redness, 0.17 for chemosis, 0.06 for iris lesions and 0.0 for corneal opacity. The observed conjunctival reactions and iris lesion (max. score = 1) were fully reversible within 48 hours.

Under the test conditions, the test material is not classified as irritating to the eyes according to the annex VI of the Regulation EC No. 1272/2008 (CLP).

Although some details on experimental conditions were missing, this study is considered as acceptable and satisfies the requirement for eye irritation endpoint.

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed (not irritating)

Respiratory irritation

Endpoint conclusion

Endpoint conclusion:

no study available

Additional information

Skin irritation:

A key study was identified (Consumer Product Testing, 1978). This dermal irritation study was performed following the Draize procedure. Worst-case conditions were used (24 h occlusive exposure) and observation were performed at 24 and 72h only. However only slight effects were observed after 24 hours, and were completely reversible within 72 hours. A repeat study is unlikely to show worse effects, therefore this study was considered sufficiently robust to cover this endpoint.

The test material induced very slight erythema which was reversible within 72 h. The mean scores calculated for all animals within 2 scoring times (24 and 72 hours) were 0.5 for erythema and 0.0 for oedema.

Under the test conditions, the test material is not irritant to the skin.

Eye irritation:

A key study was identified (Consumer Product Testing, 1978). This eye irritation study was performed according to the Draize procedure which is similar to the current OECD Test Guideline No. 405.

The calculated mean score for all animals within 3 scoring times (24, 48 and 72 h) were 0.28 for redness, 0.17 for chemosis, 0.06 for iris lesions and 0.0 for corneal opacity. The observed conjunctival reactions and iris lesion (max. score = 1) were fully reversible within 48 hours.

Under the test conditions, the test material is not classified as irritating to the eyes.

Justification for selection of skin irritation / corrosion endpoint:
Only one study available. The key-study is GLP-compliant and of good quality (Klimisch score = 2).

Justification for selection of eye irritation endpoint:
Only one study available. The key-study is GLP-compliant and of good quality (Klimisch score = 2).

Justification for classification or non-classification

Harmonized classification:

The substance has no harmonized classification according to the Regulation (EC) No. 1272/2008 including ATP6.

Self-classification:

Based on the available data no additional self-classification is proposed regarding both skin and eye irritation according to the Annex VI of the Regulation (EC) No. 1272/2008 (CLP).

No data was available regarding respiratory irritation.