6-cyclopentylidenehexanal

Endpoint summary

Description of key information

Skin irritation: irritating (OECD 404, GLP, K, Rel.1)

Eye irritation: causes serious eye damage (OECD 405, GLP, K, Rel.1)

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 05 to 26 February 2013

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

guideline study

Remarks:

GLP study conducted in compliance with OECD Guideline No. 404 without any deviation.

Qualifier:

according to guideline

Guideline:

OECD Guideline 404 (Acute Dermal Irritation / Corrosion)

Version / remarks:

24 April 2002

Deviations:

no

Qualifier:

according to guideline

Guideline:

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

Version / remarks:

30 May 2008.

Deviations:

no

Principles of method if other than guideline:

Not applicable

GLP compliance:

yes (incl. QA statement)

Remarks:

Inspected on 2012-04-23&24 / Signed on 2012-07-18.

Specific details on test material used for the study:

- Date received: 23 January 2013
- Storage condition of test material: 6°C±3°C

Species:

rabbit

Strain:

New Zealand White

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Source: Elevage de Gérome (Quartier Labaste – F40260 Linxe).
- Weight at study initiation: 2.22 - 3.03 kg
- Housing: Each animal was kept in an individual box installed in conventional air conditioned animal husbanding.
- Diet: foodstuff (SAFE – 112), ad libitum
- Water: tap-water, ad libitum
- Acclimation period: 5 days

ENVIRONMENTAL CONDITIONS
- Temperature: 17-23 °C
- Humidity: 30-70 %
- Air changes: between ten and fifteen changes per hour.
- Photoperiod: 12 hours light/12 hours dark.

IN-LIFE DATES: From 05 to 26 February 2013.

Type of coverage:

semiocclusive

Preparation of test site:

clipped

Vehicle:

unchanged (no vehicle)

Controls:

yes

Amount / concentration applied:

TEST MATERIAL
- Amount(s) applied (volume or weight with unit): 0.5 mL
- Concentration (if solution): Test item was applied as supplied.

Duration of treatment / exposure:

4 hours

Observation period:

Skin reactions were appreciated 1, 24, 48 and 72 hours after removal of the patch and observations were continued from Days 7 to 14 (in case of persistent reactions were observed).

Number of animals:

3 males

Details on study design:

PRETEST
Initially, a single animal was treated. After consideration of the cutaneous responses produced in the first treated animal, two additional animals were treated.

TEST SITE
- Area of exposure: Undamaged skin area of the right flank of each animal
- Type of wrap if used: Patch was secured in position with a strip of surgical adhesive tape.

REMOVAL OF TEST SUBSTANCE
- Washing: After removal of the patch, the treated area was rinsed with distilled water.
- Time after start of exposure: 4 h

OBSERVATION TIME POINTS
1, 24, 48 and 72 hours after removal of the patch and observations were continued from Days 7 to 14 (in case of persistent reactions were observed).

SCORING SYSTEM:
- Method of calculation: Skin irritant reaction was scored as per Draize scale according to OECD guideline 404

Irritation parameter:

erythema score

Basis:

animal #1

Remarks:

mean individual score

Time point:

24/48/72 h

Score:

3

Max. score:

4

Reversibility:

fully reversible within: 14 days.

Remarks on result:

positive indication of irritation

Irritation parameter:

edema score

Basis:

animal #1

Remarks:

mean individual score

Time point:

24/48/72 h

Score:

3.3

Max. score:

4

Reversibility:

fully reversible within: 14 days.

Remarks on result:

positive indication of irritation

Irritation parameter:

erythema score

Basis:

animal #2

Remarks:

mean individual score

Time point:

24/48/72 h

Score:

3

Max. score:

4

Reversibility:

fully reversible within: 7 days

Remarks on result:

positive indication of irritation

Irritation parameter:

edema score

Basis:

animal #2

Remarks:

mean individual score

Time point:

24/48/72 h

Score:

2

Max. score:

4

Reversibility:

fully reversible within: 7 days

Remarks on result:

probability of mild irritation

Irritation parameter:

erythema score

Basis:

animal #3

Remarks:

mean individual score

Time point:

24/48/72 h

Score:

3

Max. score:

4

Reversibility:

fully reversible within: 7 days

Remarks on result:

positive indication of irritation

Irritation parameter:

edema score

Basis:

animal #3

Remarks:

mean individual score

Time point:

24/48/72 h

Score:

2.3

Max. score:

4

Reversibility:

fully reversible within: 7 days

Remarks on result:

positive indication of irritation

Irritant / corrosive response data:

- A moderate erythema associated with a slight to severe oedema was noted on the treated area of the animals 24 hours after the patch removal.
- The erythematous and oedematous reactions were totally reversible between days 7 and 14. Dryness was noted from days 3 and 7 and was totally reversible on day 14.

Other effects:

None

Table 7.3.1/1: Individual and mean skin reactions/Erythema - Eschar formation following 4 hour exposure

Skin reaction	Observation time (following patch removal)	Individual Scores – Rabbit Number and Sex
		A2768/Male	A2796/Male	A2797/Male
Erythema/Eschar formation	1 h	2	2	3
	24 h	3	3	3
	48 h	3	3	3
	72 h	3	3	3
	Day 7	1	0	0
	Day 14	0	0	0
	Total (24, 48 and 72 hours)	9	9	9
	Mean (24, 48 and 72 hours)	3	3	3

Table 7.3.1/2: Individual and mean skin reactions/Oedema formation following 4 hour exposure

Skin reaction	Observation time (following patch removal)	Individual Scores – Rabbit Number and Sex
		A2768/Male	A2796/Male	A2797/Male
Oedema formation	1 h	3	3	3
	24 h	4	2	3
	48 h	3	2	2
	72 h	3	2	2
	Day 7	1	0	0
	Day 14	0	0	0
	Total (24, 48 and 72 hours)	10	6	7
	Mean (24, 48 and 72 hours)	3.3	2	2.3

Note:

A2768: dryness from D3 to D7

A2796: dryness at D7

A2797: dryness from at D7

Interpretation of results:

Category 2 (irritant) based on GHS criteria

Conclusions:

Under the test conditions, the test material is classified as irritant to the skin according to the Annex I of the Regulation EC No. 1272/2008 (CLP) and to the GHS.

Executive summary:

In a dermal irritation study performed according to the OECD Guideline No. 404, and in compliance with GLP, 0.5 mL of undiluted test item was applied on an undamaged skin area of the flank of 3 male New Zealand White rabbits. On the other flank an untreated area was served as the control. Test sites were covered with a semi-occlusive dressing for 4 h. Skin irritation was assessed and scored according to the Draize scale at 1, 24, 48 and 72 hours after removal of the patch and observations were continued from Days 7 to 14. Initially, a single animal was treated. After consideration of the cutaneous responses produced in the first treated animal, two additional animals were treated.

 

A moderate erythema associated with a slight to severe oedema was noted on the treated area of the animals 24 hours after the patch removal. The erythematous and oedematous reactions were totally reversible between days 7 and 14. Dryness was noted from days 3 and 7 and was totally reversible on day 14.

The mean scores for each animal within 3 scoring times (24, 48 and 72 h) were 3 / 3 / 3 for erythema and 3.3 / 2 / 2.3 for oedema.

Therefore, the test material is classified as irritating to the skin in category 2 according to the Annex I of the Regulation EC No. 1272/2008 (CLP) and to the GHS.

This study is considered as acceptable and satisfies the requirement for skin irritation endpoint.

Endpoint conclusion

Endpoint conclusion:

adverse effect observed (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:

Between 11 February and 04 March 2013.

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

guideline study

Remarks:

GLP study conducted in compliance with OECD Guideline No. 405 without any deviation.

Qualifier:

according to guideline

Guideline:

OECD Guideline 405 (Acute Eye Irritation / Corrosion)

Version / remarks:

24 April 2002.

Deviations:

no

Qualifier:

according to guideline

Guideline:

EU Method B.5 (Acute Toxicity: Eye Irritation / Corrosion)

Deviations:

no

Principles of method if other than guideline:

Not applicable

GLP compliance:

yes (incl. QA statement)

Remarks:

Inspected on 2012-04-23&24 / Signed on 2012-07-18.

Specific details on test material used for the study:

- Date received: 23 January 2013
- Storage condition of test material: 6°C±3°C

Species:

rabbit

Strain:

New Zealand White

Details on test animals or tissues and environmental conditions:

TEST ANIMALS
- Source: Elevage de Gérome (Quartier Labaste – F40260 Linxe).
- Weight at study initiation: 2.81-2.91 kg
- Housing: the animal was kept in an individual box installed in conventional air conditioned animal husbanding.
- Diet: foodstuff (SAFE - 112), ad libitum
- Water: tap-water, ad libitum
- Acclimation period: 5 day

ENVIRONMENTAL CONDITIONS
- Temperature: 17-23 °C
- Humidity: 30-70 %
- Air changes: between ten and fifteen changes per hour.
- Photoperiod: 12 hours light/12 hours dark.

IN-LIFE DATES: from 11 February to 04 March 2013.

Vehicle:

unchanged (no vehicle)

Controls:

yes

Amount / concentration applied:

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

- Concentration (if solution): Test item was instilled, as supplied

Duration of treatment / exposure:

No washing was done

Observation period (in vivo):

Ocular examinations were performed on both right and left eyes 1, 24, 48 and 72 h & Days 7, 14 and 21 following treatment, according to a numerical evaluation.

Number of animals or in vitro replicates:

1

Details on study design:

TREATMENT
- 0.1 mL of the test item was instilled, as supplied, into the conjunctival sac of one eye. The other eye remained untreated serving as control.
- Initially, a single animal was treated. After consideration of the responses produced on day 21 in the first animal, two additional animals were not treated.

REMOVAL OF TEST SUBSTANCE
- Washing: No

SCORING SYSTEM: According to OECD guideline 405

Irritation parameter:

cornea opacity score

Basis:

animal #1

Remarks:

mean individual score

Time point:

24/48/72 h

Score:

2

Max. score:

4

Reversibility:

not fully reversible within: 21 days

Remarks on result:

probability of severe irritation

Irritation parameter:

iris score

Basis:

animal #1

Remarks:

mean individual score

Time point:

24/48/72 h

Score:

1

Max. score:

2

Reversibility:

fully reversible within: 7 days.

Remarks on result:

probability of mild irritation

Irritation parameter:

conjunctivae score

Basis:

animal #1

Remarks:

mean individual score

Time point:

24/48/72 h

Score:

3

Max. score:

3

Reversibility:

fully reversible within: 21 days

Remarks on result:

positive indication of irritation

Irritation parameter:

chemosis score

Basis:

animal #1

Remarks:

mean individual score

Time point:

24/48/72 h

Score:

2.3

Max. score:

4

Reversibility:

fully reversible within: 21 days

Remarks on result:

positive indication of irritation

Irritant / corrosive response data:

The ocular reactions observed during the study have been moderate to important and partially reversible:
- at the conjunctivae level: an important redness, noted 1 hour after the test item instillation and totally reversible on day 21, associated with an important chemosis, noted 1 hour after the test item instillation and totally reversible on day 21.
- at the iris level: a congestion, noted 1 hour after the test item instillation and totally reversible on day 7.
- at the corneal level: a moderate corneal opacity, noted 1 hour after the test item instillation and remaining on the last day of the test (day 21) with an important intensity.
A corneal neovascularization was noted on day 7 and was still observed on day 21.

Other effects:

None

Table 7.3.2/1: Individual and Mean Scores for Cornea, Iris and Conjunctivae

Rabbit Number and Sex	Time After Treatment	Corneal Opacity	Iris lesion	Conjunctival Redness	Conjunctival Chemosis
A2784 Female	1 h	2	1	3	3
	24 h	2	1	3	3
	48 h	2	1	3	2
	72 h	2	1	3	2
	Day 7	3	0	2	2
	Day 14	3	0	1	1
	Day 21	3	0	0	0
	Total (24, 48 and 72 h)	6	3	9	7
	Mean (24, 48 and 72 h)	2	1	3	2.3

Interpretation of results:

Category 1 (irreversible effects on the eye) based on GHS criteria

Conclusions:

Under the test conditions, test material causes serious eye damage and classified in category 1 according to the annex I of the Regulation (EC) No. 1272 /2008 (CLP) and to the GHS.

Executive summary:

In an eye irritation study conducted according to OECD 405 guideline and in compliance with GLP, 1 New Zealand White female rabbit was exposed to 0.1 mL of test item in one eye while the contralateral eye remained untreated and served as control. The eyes were examined and the changes were observed at 1, 24, 48 and 72 h and from 7 to 21 days following treatment and graded according to the Draize method. Initially, a single animal was treated. After consideration of the responses produced on day 21 in the first animal, two additional animals were not treated.

At the conjunctivae level, an important redness was noted 1 hour after the test item instillation and totally reversible on day 21, associated with an important chemosis, noted 1 hour after the test item instillation and totally reversible on day 21. At the iris level, a congestion was noted 1 hour after the test item instillation and totally reversible on day 7. At the corneal level, a moderate corneal opacity was noted 1 hour after the test item instillation and remaining on the last day of the test (day 21) with an important intensity. A corneal neovascularization was noted on day 7 and was still observed on day 21.

 

Mean scores at 24, 48 and 72 h after exposure for one animal were 2.0, 1.0, 3.0, 2.3 for cornea, iris, conjunctivae and chemosis respectively.

 

Under the test conditions, test material causes serious eye damage and classified in category 1 according to the annex I of the Regulation (EC) No. 1272 /2008 (CLP) and to the GHS.

This study is considered as acceptable and satisfies the requirement for eye irritation endpoint.

Endpoint conclusion

Endpoint conclusion:

adverse effect observed (irreversible damage)

Respiratory irritation

Endpoint conclusion

Endpoint conclusion:

no study available

Additional information

Skin irritation:

A key study was identified (Phycher, 2013). In this dermal irritation study performed according to the OECD Guideline No. 404, and in compliance with GLP, 3 female New Zealand White rabbits were exposed for 4 hours to a semi-occluded application of 0.5 mL of undiluted test item was applied on an undamaged skin area of the flank of 3 male New Zealand White rabbits. On the other flank an untreated area was served as the control. Test sites were covered with a semi-occlusive dressing for 4 h. Skin irritation was assessed and scored according to the Draize scale at 1, 24, 48 and 72 hours after removal of the patch and observations were continued from Days 7 to 14. Initially, a single animal was treated. After consideration of the cutaneous responses produced in the first treated animal, two additional animals were treated.

 

A moderate erythema associated with a slight to severe oedema was noted on the treated area of the animals 24 hours after the patch removal. The erythematous and oedematous reactions were totally reversible between days 7 and 14. Dryness was noted from days 3 and 7 and was totally reversible on day 14.

The mean scores for each animal within 3 scoring times (24, 48 and 72 h) were 3 / 3 / 3 for erythema and 3.3 / 2 / 2.3 for oedema.

 

Eye irritation:

A key study was identified (Phycher, 2013). In this eye irritation study performed according to the OECD guideline 405, and in compliance with GLP,

0.1 mL of test item in one eye while the contralateral eye remained untreated and served as control. The eyes were examined and the changes were observed at 1, 24, 48 and 72 h and from 7 to 21 days following treatment and graded according to the Draize method. Initially, a single animal was treated.After consideration of the responses produced on day 21 in the first animal, two additional animals were not treated.

At the conjunctivae level, an important redness was noted 1 hour after the test item instillation and totally reversible on day 21, associated with an important chemosis, noted 1 hour after the test item instillation and totally reversible on day 21. At the iris level, a congestion was noted 1 hour after the test item instillation and totally reversible on day 7. At the corneal level, a moderate corneal opacity was noted 1 hour after the test item instillation and remaining on the last day of the test (day 21) with an important intensity. A corneal neovascularization was noted on day 7 and was still observed on day 21.

 

Mean scores at 24, 48 and 72 h after exposure for one animal were 2.0, 1.0, 3.0, 2.3 for cornea, iris, conjunctivae and chemosis respectively.

Justification for classification or non-classification

 

Harmonized classification:

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

 

Self classification:

Skin irritation:

Based on the available data, the substance should be classified as skin irritation Category 2 (H315: Causes skin irritation) according to the CLP and to the GHS.

 

Eye irritation:

Based on the available data, the substance should be classified as eye irritation Category 1 (H318: Causes serious eye damage) according to the CLP and to the GHS.

 

Respiratory irritation:

No data was available regarding respiratory irritation.