5-hept-6-enyloxolan-2-one

Endpoint summary

Description of key information

Skin irritation: not irritating (OECD 404, GLP, K, Rel.1)

Eye irritation: not irritating (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:

14 to 24 December 2004.

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

guideline study

Remarks:

GLP study conducted in compliance with OECD Guideline No. 404 with minor deviations: details on feeding and environmental conditions not reported. The substance is adequately identified. Therefore full validation applies.

Qualifier:

according to guideline

Guideline:

OECD Guideline 404 (Acute Dermal Irritation / Corrosion)

Version / remarks:

April 24th, 2002

Deviations:

yes

Remarks:

details on feeding and environmental conditions not reported

Qualifier:

according to guideline

Guideline:

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

Version / remarks:

directive n° 2004/73/EC

Deviations:

yes

Remarks:

details on feeding and environmental conditions not reported

Principles of method if other than guideline:

Not applicable

GLP compliance:

yes (incl. QA statement)

Remarks:

Inspected on 2004-07-01 / Signed on 2004-09-13

Specific details on test material used for the study:

- Date received: 09 December 2004

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: 2.19-2.44 kg
- Housing: Each animal was kept in an individual box installed in conventional air conditioned animal husbanding.
- Diet: No data
- Water: No data
- Acclimation period: 5 days

ENVIRONMENTAL CONDITIONS
- Temperature: 19-21 °C
- Humidity: 28-54 %
- Air changes: No data
- Photoperiod: No data

IN-LIFE DATES: From 14 To 24 December 2004

Type of coverage:

semiocclusive

Preparation of test site:

not specified

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 4 to 14.

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 4 to 14.

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:

0

Max. score:

4

Reversibility:

other: Not applicable

Remarks on result:

no indication of irritation

Irritation parameter:

edema score

Basis:

animal #1

Remarks:

mean individual score

Time point:

24/48/72 h

Score:

0

Max. score:

4

Reversibility:

other: Not applicable

Remarks on result:

no indication of irritation

Irritation parameter:

erythema score

Basis:

animal #2

Remarks:

mean individual score

Time point:

24/48/72 h

Score:

0.3

Max. score:

4

Reversibility:

fully reversible within: 2 days

Remarks on result:

probability of mild irritation

Irritation parameter:

edema score

Basis:

animal #2

Remarks:

mean individual score

Time point:

24/48/72 h

Score:

0

Max. score:

4

Reversibility:

other: Not applicable

Remarks on result:

no indication of irritation

Irritation parameter:

erythema score

Basis:

animal #3

Remarks:

mean individual score

Time point:

24/48/72 h

Score:

0

Max. score:

4

Reversibility:

other: Not applicable

Remarks on result:

no indication of irritation

Irritation parameter:

edema score

Basis:

animal #3

Remarks:

mean individual score

Time point:

24/48/72 h

Score:

0

Max. score:

4

Reversibility:

other: Not applicable

Remarks on result:

no indication of irritation

Irritant / corrosive response data:

It was only noted a slight erythema, in one animal, at the examination time 24 hours.

Other effects:

None

Table 7.3.1/1: Individual and average scores after 4 h exposure

Observations		Score
Skin reactions	Observation time	Animal no. A6366	Animal no. A6373	Animal no. A6396
Erythema and eschar	24 h	0	1	0
	48 h	0	0	0
	72 h	0	0	0
	Total (24, 48 and 72 h)	0	1	0
	Mean (24, 48 and 72 h)	0.0	0.3	0.0
Oedema formation	24h	0	0	0
	48 h	0	0	0
	72 h	0	0	0
	Total (24, 48 and 72 h)	0	0	0
	Mean (24, 48 and 72 h)	0.0	0.0	0.0

Interpretation of results:

GHS criteria not met

Conclusions:

Under these experimental conditions, test item must not be classified according to the CLP Regulation (EC) No. 1272/2008 and Globally Harmonized System (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 right flank of 3 male New Zealand White rabbits. On the left 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. Initially, a single animal was treated. After consideration of the cutaneous responses produced in the first treated animal, two additional animals were treated.

 

It was only noted a slight erythema, in one animal, at the examination time 24 hours. This reaction was totally reversible on day 2.

 

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

 

Under these experimental conditions, test item must not be classified according to the CLP Regulation (EC) No. 1272 /2008 and Globally Harmonized System (GHS).

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:

Between 20 and 30 December, 2004.

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

guideline study

Remarks:

GLP study conducted according to OECD 405 Guideline. However, details on feeding and environmental conditions and isomers ratio are not reported. The substance is adequately identified. Therefore full validation applies.

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)

Version / remarks:

Directive n° 2004/73/EC.

Deviations:

no

Principles of method if other than guideline:

Not applicable

GLP compliance:

yes (incl. QA statement)

Remarks:

Inspected on 2004-07-01 / Signed on 2004-09-13.

Specific details on test material used for the study:

- Date received: 09 December 2004

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)
- Age at study initiation: no data
- Weight at study initiation: 2.37-2.53 kg
- Housing: Each animal was kept in an individual box installed in conventional air conditioned animal husbanding.
- Diet: no data
- Water: no data
- Acclimation period: 5 days

ENVIRONMENTAL CONDITIONS
- Temperature: 20–21°C
- Humidity: 30-52 %
- Air changes: no data
- Photoperiod: no data

IN-LIFE DATES: From 20 to 30 December, 2004.

Vehicle:

unchanged (no vehicle)

Controls:

other: untreated eye serving as control

Amount / concentration applied:

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

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 following treatment, according to a numerical evaluation.

Number of animals or in vitro replicates:

3 females

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 ocular responses produced in the first treated animal, two additional animals were 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:

0

Max. score:

4

Reversibility:

other: Not applicable

Remarks on result:

no indication of irritation

Irritation parameter:

iris score

Basis:

animal #1

Remarks:

mean individual score

Time point:

24/48/72 h

Score:

0

Max. score:

2

Reversibility:

other: Not applicable

Remarks on result:

no indication of irritation

Irritation parameter:

conjunctivae score

Basis:

animal #1

Remarks:

mean individual score

Time point:

24/48/72 h

Score:

0.3

Max. score:

3

Reversibility:

fully reversible within: 2 days

Remarks on result:

probability of weak irritation

Irritation parameter:

chemosis score

Basis:

animal #1

Remarks:

mean individual score

Time point:

24/48/72 h

Score:

0

Max. score:

4

Reversibility:

other: Not applicable

Remarks on result:

no indication of irritation

Irritation parameter:

cornea opacity score

Basis:

animal #2

Remarks:

mean individual score

Time point:

24/48/72 h

Score:

0

Max. score:

4

Reversibility:

other: Not applicable

Remarks on result:

no indication of irritation

Irritation parameter:

iris score

Basis:

animal #2

Remarks:

mean individual score

Time point:

24/48/72 h

Score:

0

Max. score:

2

Reversibility:

other: Not applicable

Remarks on result:

no indication of irritation

Irritation parameter:

conjunctivae score

Basis:

animal #2

Remarks:

mean individual score

Time point:

24/48/72 h

Score:

0.3

Max. score:

3

Reversibility:

fully reversible within: 2 days

Remarks on result:

probability of weak irritation

Irritation parameter:

chemosis score

Basis:

animal #2

Remarks:

mean individual score

Time point:

24/48/72 h

Score:

0

Max. score:

4

Reversibility:

other: Not applicable

Remarks on result:

no indication of irritation

Irritation parameter:

cornea opacity score

Basis:

animal #3

Remarks:

mean individual score

Time point:

24/48/72 h

Score:

0

Max. score:

4

Reversibility:

other: Not applicable

Remarks on result:

no indication of irritation

Irritation parameter:

iris score

Basis:

animal #3

Remarks:

mean individual score

Time point:

24/48/72 h

Score:

0

Max. score:

2

Reversibility:

other: Not applicable

Remarks on result:

no indication of irritation

Irritation parameter:

conjunctivae score

Basis:

animal #3

Remarks:

mean individual score

Time point:

24/48/72 h

Score:

0.3

Max. score:

3

Reversibility:

fully reversible within: 2 days

Remarks on result:

probability of weak irritation

Irritation parameter:

chemosis score

Basis:

animal #3

Remarks:

mean individual score

Time point:

24/48/72 h

Score:

0

Max. score:

4

Reversibility:

other: Not applicable

Remarks on result:

no indication of irritation

Irritant / corrosive response data:

It was only recorded slight conjunctivae reactions, similar in the 3 animals and rapidly reversible:a slight enanthema noted 1 hour and 24 hours after the test product instillation associated with a discharge and a slight chemosis only noted 1 hour after the test product instillation.

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
A6399 Female	1 h	0	0	1	1
	24 h	0	0	1	0
	48 h	0	0	0	0
	72 h	0	0	0	0
	Total (24, 48 and 72 h)	0	0	1	0
	Mean (24, 48 and 72 h)	0	0	0.3	0

 

Rabbit Number and Sex	Time After Treatment	Corneal Opacity	Iris lesion	Conjunctival Redness	Conjunctival Chemosis
A6407 Female	1 h	0	0	1	1
	24 h	0	0	1	0
	48 h	0	0	0	0
	72 h	0	0	0	0
	Total (24, 48 and 72 h)	0	0	1	0
	Mean (24, 48 and 72 h)	0	0	0.3	0

 

Rabbit Number and Sex	Time After Treatment	Corneal Opacity	Iris lesion	Conjunctival Redness	Conjunctival Chemosis
A6408 Female	1 h	0	0	1	1
	24 h	0	0	1	0
	48 h	0	0	0	0
	72 h	0	0	0	0
	Total (24, 48 and 72 h)	0	0	1	0
	Mean (24, 48 and 72 h)	0	0	0.3	0

Interpretation of results:

GHS criteria not met

Conclusions:

Under the test conditions, the test item must not be classified according to CLP Regulation (EC) No. 1272/2008 and Globally Harmonized System (GHS).

Executive summary:

In an eye irritation study conducted according to OECD 405 guideline and in compliance with GLP, 3 New Zealand White female rabbits were 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 following treatment and graded according to the Draize method. Initially, a single animal was treated. After consideration of the ocular responses produced in the first treated animal, two additional animals were treated.

 

It was only recorded slight conjunctivae reactions, similar in the 3 animals and rapidly reversible:a slight enanthema noted 1 hour and 24 hours after the test product instillation associated with a discharge and a slight chemosis only noted 1 hour after the test product instillation.

 

Mean individual scores at 24, 48 and 72 h after exposure for the 3 animals were 0.0, 0.0, 0.0 for cornea score; 0.0, 0.0, 0.0 for iris score; 0.3, 0.3, 0.3 for conjunctivae score and 0.0, 0.0, 0.0 for chemosis score.

 

Under the test conditions, test item must not be classified according to CLP Regulation (EC) No. 1272 /2008 and Globally Harmonized System (GHS).

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 (Phycher, 2005). In this dermal irritation study performed according to the OECD Guideline No. 404, and in compliance with GLP, 3 male New Zealand White rabbits were exposed for 4 hours to a semi-occluded application of 0.5 mL of undiluted test material to the intact skin. Skin irritation was assessed and scored according to the Draize scale at 1, 24, 48 and 72 hours after removal of the patch. Initially, a single animal was treated. After consideration of the cutaneous responses produced in the first treated animal, two additional animals were treated.

 

It was only noted a slight erythema, in one animal, at the examination time 24 hours. This reaction was totally reversible on day 2.

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

 

Eye irritation:

A key study was identified (Phycher, 2005). In this eye irritation study performed according to the OECD guideline 405, and in compliance with GLP, 0.1 mL of undiluted test material was instilled into one eye of 3 female New Zealand White rabbits. The other eye remained untreated and served as control. The eyes were examined and the changes were observed at 1, 24, 48 and 72 h following treatment and graded according to the Draize method. Initially, a single animal was treated. After consideration of the ocular responses produced in the first treated animal, two additional animals were treated.

It was only recorded slight conjunctivae reactions, similar in the 3 animals and rapidly reversible:a slight enanthema noted 1 hour and 24 hours after the test product instillation associated with a discharge and a slight chemosis only noted 1 hour after the test product instillation.

 

Mean individual scores at 24, 48 and 72 h after exposure for the 3 animals were 0.0, 0.0, 0.0 for cornea score; 0.0, 0.0, 0.0 for iris score; 0.3, 0.3, 0.3 for conjunctivae score and 0.0, 0.0, 0.0 for chemosis score.

 

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, no additional self-classification is proposed regarding skin irritation according to the CLP and to the GHS.

 

Eye irritation:

Based on the available data, no additional self-classification is proposed regarding eye irritation according to the CLP and to the GHS.

 

Respiratory irritation:

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.