2,2,5-trimethyl-5-pentylcyclopentan-1-one

Endpoint summary

Description of key information

Skin irritation/corrosion: not irritating (OECD 404, GLP, K, rel. 1).
Eye irritation: not irritating (similar to OECD 405, K, rel.2).

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:

From July 03 to 12, 2001

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

other: GLP study conducted in compliance with OECD Guideline No. 404 without any deviations.

Reason / purpose for cross-reference:

reference to same study

Reason / purpose for cross-reference:

reference to other study

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

Principles of method if other than guideline:

Not applicable

GLP compliance:

yes (incl. QA statement)

Remarks:

inspected on September 22, 1999/signed on January 18, 2000

Species:

rabbit

Strain:

New Zealand White

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Source: CEGAV, Saint Mars d'Egrenne, France.
- Weight at study initiation: Mean body weight: 2.8 ± 0.1 kg
- Housing: Animals were housed individually in polystyrene cages (48.2 cm x 58 cm x 36.5 cm).
- Diet: 110 pelleted diet (UAR, Villemoisson, Epinay sur-Orge, France), ad libitum
- Water: Drinking water (filtered by a FG Millipore membrane (0.22 µm)), ad libitum
- Acclimation period: 5 days

ENVIRONMENTAL CONDITIONS
- Temperature: 18 ± 3 °C
- Humidity: 30-70 %
- Air changes: Approximately 12 cycles/hour of filtered, non-recycled air
- Photoperiod: 12 h dark/ 12 h light

IN-LIFE DATES: From: July 03, 2001 To: July 12, 2001

Type of coverage:

semiocclusive

Preparation of test site:

clipped

Vehicle:

unchanged (no vehicle)

Controls:

other: untreated skin served as control

Amount / concentration applied:

TEST MATERIAL
- Amount(s) applied (volume or weight with unit): 0.5 mL
- Concentration (if solution): Undiluted

Duration of treatment / exposure:

4 h

Observation period:

1, 24, 48 and 72 h after patch-removal. Since there was a persistent irritation reaction at 72 h, the observation period was extended up to their complete reversibility (Day 10).

Number of animals:

3 males

Details on study design:

TEST SITE
- Area of exposure: Right flank
- Type of wrap if used: Test substance was placed on the gauze pad and held in contact with the skin by means of an adhesive hypoallergenic aerated semi-occlusive dressing and a restraining bandage.

REMOVAL OF TEST SUBSTANCE
- Washing (if done): No; no residual test substance was observed on removal of the dressing.
- Time after start of exposure: 4 h

SCORING SYSTEM: Draize scale, as described in OECD Guideline 404

Irritation parameter:

erythema score

Basis:

animal #1

Time point:

other: Mean 24, 48 and 72 h

Score:

2

Max. score:

4

Reversibility:

fully reversible within: 10 days

Irritation parameter:

edema score

Basis:

animal #1

Time point:

other: Mean 24, 48 and 72 h

Score:

0.3

Max. score:

4

Reversibility:

fully reversible within: 48 h

Irritation parameter:

erythema score

Basis:

animal #2

Time point:

other: Mean 24, 48 and 72 h

Score:

1

Max. score:

4

Reversibility:

fully reversible within: 7 days

Irritation parameter:

edema score

Basis:

animal #2

Time point:

other: Mean 24, 48 and 72 h

Score:

0

Max. score:

4

Reversibility:

fully reversible within: 24 h

Irritation parameter:

erythema score

Basis:

animal #3

Time point:

other: Mean 24, 48 and 72 h

Score:

1

Max. score:

4

Reversibility:

fully reversible within: 7 days

Irritation parameter:

edema score

Basis:

animal #3

Time point:

other: Mean 24, 48 and 72 h

Score:

0

Max. score:

4

Reversibility:

fully reversible within: 24 h

Irritant / corrosive response data:

- A well-defined erythema (grade 2), in addition to a slight oedema (grade 2), was observed on Day 1 in all the animals.
- A well-defined erythema (grade 2) persisted in 1/3 animals from Day 2-6; a very slight erythema (grade 1) was then noted until Day 9. A very slight oedema (grade 1) was also observed on Day 2. In both remaining animals, a very slight erythema (grade 1) was recorded from Day 2-6.
- A dryness of the skin was observed in all the animals from Day 4 (two animals) or 7 to Day 9. Crusts were also noted in 1/3 animals on Days 5 and 6.

Other effects:

None

Table 7.3.1/1: Mean skin irritant/corrosive response data for each animal at each observation time up to removal of animals from the test

Score at time point	Erythema (Animal No. 1 / 2 / 3) Max. score 4	Oedema (Animal No. 1 / 2 / 3) Max. score 4	Other (Animal No. 1 / 2 / 3)
1 h	2/2/2	2/2/2	*/*/*
24 h	2/1/1	1/0/0	*/*/*
48 h	2/1/1	0/0/0	*/*/*
72 h	2/1/1	0/0/0	*/S/S
Day 5	2/1/1	0/0/0	*/SA/S
Day 6	2/1/1	0/0/0	*/SA/S
Day 7	1/0/0	0/0/0	S/S/S
Day 8	1/0/0	0/0/0	S/S/S
Day 9	1/0/0	0/0/0	S/S/S
Day 10	0/0/0	0/0/0	*/*/*
Average 24, 48 and 72 h	2/1/1	0.3/0/0	-
Reversibility	Completely reversible	Completely reversible	-
Average time for reversion	10 days	48 h	-

 

Keys: * None; S= Dryness of the skin; A= Crust

Interpretation of results:

not irritating

Remarks:

Migrated information Criteria used for interpretation of results: EU

Conclusions:

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

Executive summary:

In a dermal irritation study performed according to the OECD Guideline No. 404, and in compliance with GLP, 0.5 mL of the undiluted test material was applied on the clipped skin of the right flank area of three male New Zealand White rabbits. The test material was held in contact with the skin by means of a semi-occlusive dressing for 4 h. The untreated skin served as control. Cutaneous reactions were assessed and scored according to the Draize scale at 1, 24, 48 and 72 h after removal of the dressing and then daily until reversibility of cutaneous reactions (Day 10).

A well-defined erythema, in addition to a slight oedema, was observed on Day 1 in all the animals. A well-defined erythema persisted in 1/3 animals from Day 2-6; a very slight erythema was then noted until Day 9. A very slight oedema was also observed on Day 2. In both remaining animals, a very slight erythema was recorded from Day 2-6. A dryness of the skin was observed in all the animals from Day 4 (two animals) or 7, to Day 9. Crusts were also noted in 1/3 animals on Days 5 and 6.

The individual scores for each animal within 3 scoring times (24, 48 and 72 h) were 2.0 / 1.0 / 1.0 for erythema and 0.3 / 0.0 / 0.0 for oedema.

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

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 July 23 to 26, 1979

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

other: Basic data given: comparable to standard guideline with the following deviations: 6 animals tested instead of 3. This deviation does not affect the reliability of this study.

Reason / purpose for cross-reference:

reference to same study

Reason / purpose for cross-reference:

reference to other study

Qualifier:

equivalent or similar to guideline

Guideline:

OECD Guideline 405 (Acute Eye Irritation / Corrosion)

Deviations:

yes

Remarks:

6 animals tested

Principles of method if other than guideline:

Study was performed according to modified Draize procedure (Draize, 1975).

GLP compliance:

no

Remarks:

(pre-GLP)

Species:

rabbit

Strain:

New Zealand White

Details on test animals or tissues and environmental conditions:

TEST ANIMALS
- Age at study initiation: About 3 months
- Weight at study initiation: Approximately 2 kg
- Housing: Animals were housed in galvanized or stainless steel cages.
- Diet: Diet consisted of a growth and maintenance ration from a commercial producer, ad libitum
- Water, ad libitum
- Acclimation period: 3 days

IN-LIFE DATES: From: July 23, 1979 To: July 26, 1979

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 eyes of all animals remained unwashed for 24 h.

Observation period (in vivo):

24, 48, and 72 h 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: No data

Irritation parameter:

cornea opacity score

Basis:

animal: #1, #2, #3, #4, #5 & #6

Time point:

other: Mean 24, 48 and 72 h

Score:

0

Max. score:

4

Irritation parameter:

iris score

Basis:

animal: #1, #2, #3, #4, #5 & #6

Time point:

other: Mean 24, 48 and 72 h

Score:

0

Max. score:

2

Irritation parameter:

conjunctivae score

Basis:

animal: #1, #2, #3, #4 & #6

Time point:

other: Mean 24, 48 and 72 h

Score:

0.33

Max. score:

3

Reversibility:

fully reversible within: 2 days

Irritation parameter:

conjunctivae score

Basis:

animal #5

Time point:

other: Mean 24, 48 and 72 h

Score:

0

Max. score:

3

Irritation parameter:

chemosis score

Basis:

animal: #4 & #6

Time point:

other: Mean 24, 48 and 72 h

Score:

1

Max. score:

4

Reversibility:

fully reversible within: 2 days

Irritation parameter:

chemosis score

Basis:

animal: #1, #2, #3 & #5

Time point:

other: Mean 24, 48 and 72 h

Score:

0

Max. score:

4

Irritant / corrosive response data:

- Animals showed conjunctival reactions (redness and chemosis) which were reversible within 2 days

Other effects:

-None

Table 7.3.2/1: 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)
24 h (Day 1)	0 / 0 / 0 / 0 / 0 / 0	0 / 0 / 0 / 0 / 0 / 0	0 / 0 / 0 / 0 / 0 / 0	1 / 1 / 1 / 1 / 0 / 1	0 / 0 / 0 / 1 / 0 / 1	0 / 0 / 0 / 0 / 0 / 0
48 h (Day 2)	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
72 h (Day 3)	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 24h, 48h, and 72h	0 / 0 / 0 / 0 / 0 / 0	0 / 0 / 0 / 0 / 0 / 0	0 / 0 / 0 / 0 / 0 / 0	0.33 / 0.33 / 0.33 / 0.33 / 0 / 0.33	0 / 0 / 0 / 0.33 / 0 / 0.33	0 / 0 / 0 / 0 / 0 / 0
Reversibility	-	-	-	Completely reversible	Completely reversible	-
Average time (unit) for reversion	-	-	-	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 induced slight irritation being reversible within 2 days. Therefore, the test material is not classified as irritant to the eyes according to the Annex VI of the Regulation (EC) No. 1272/2008.

Executive summary:

In an eye irritation study, 0.1 mL of undiluted test material was instilled into the one eye of 6 albino rabbits while the contralateral eye remained untreated and served as control. The eyes were not rinsed after the instillation of test material. 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 each animal within 3 scoring times (24, 48 and 72 h) were 0.33/0.33/0.33/0.33/0.00/0.33 for redness, 0.00/0.00/0.00/0.33/0.00/0.33 for chemosis, and 0/0/0/0/0/0 for iris lesions and corneal opacity. The conjunctival reactions were fully reversible within 2 days. 

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).

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 (CIT, 2001, K1). This dermal irritation study was performed according to the OECD Guideline No. 404, and in compliance with GLP.

A well-defined erythema, in addition to a slight oedema, was observed on Day 1 in all the animals. A well-defined erythema persisted in 1/3 animals from Day 2-6; a very slight erythema was then noted until Day 9. A very slight oedema was also observed on Day 2. In both remaining animals, a very slight erythema was recorded from Day 2-6. A dryness of the skin was observed in all the animals from Day 4 (two animals) or 7, to Day 9. Crusts were also noted in 1/3 animals on Days 5 and 6.

The individual scores for each animal within 3 scoring times (24, 48 and 72 h) were 2.0 / 1.0 / 1.0 for erythema and 0.3 / 0.0 / 0.0 for oedema.

The registered substance is therefore not classified for skin irritation.

Eye irritation:

A key study was identified (Consumer Product Testing, 1979, rel.2). This eye irritation study was conducted similarly to OECD Guideline No. 405, with one deviation (6 animals tested instead of 3) that does not affect the reliability of the study.

The calculated mean score for each animal within 3 scoring times (24, 48 and 72 h) were 0.33/0.33/0.33/0.33/0.00/0.33 for redness, 0.00/0.00/0.00/0.33/0.00/0.33 for chemosis, and 0/0/0/0/0/0 for iris lesions and corneal opacity. The conjunctival reactions were fully reversible within 2 days.

The registered substance is therefore not classified for eye irritation.

Justification for selection of skin irritation / corrosion endpoint:
Only one study available, GLP-compliant and of high quality (Klimisch score = 1).

Justification for selection of eye irritation endpoint:
The key study performed on the registered substance in rats was pre-guideline and pre-GLP, but was performed similarly to OECD Guideline No. 405. This study was considered sufficiently robust to cover this endpoint.

Justification for classification or non-classification

Harmonized classification:

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

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, however the substance not being classified for skin and eye irritation, no classification is expected for respiratory irritation.