5-propyloxan-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:

21 March to 07 April 2006

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

guideline study

Remarks:

GLP study conducted according to OECD Guideline 404 with deviations: age at study initiation, feeding conditions not reported. These deviations do not affect the quality of the study and are not considered to be relevant.

Qualifier:

according to guideline

Guideline:

OECD Guideline 404 (Acute Dermal Irritation / Corrosion)

Version / remarks:

24 April 2002.

Deviations:

yes

Remarks:

age at study initiation, feeding 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:

age at study initiation, feeding conditions not reported.

Principles of method if other than guideline:

Not applicable

GLP compliance:

yes (incl. QA statement)

Remarks:

Inspected on 2005-10-03 / Signed on 2005-12-13.

Specific details on test material used for the study:

- Test item was considered at 100% for the study.

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: 2.48-2.86 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: 19-23 °C
- Humidity: 30-59 %

IN-LIFE DATES: 21 March to 07 April 2006

Type of coverage:

semiocclusive

Preparation of test site:

not specified

Vehicle:

unchanged (no vehicle)

Controls:

other: On the left flank an untreated area was served as the 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:

Skin reactions were appreciated 1 hour and then 24, 48, 72 hours and Days 4 to 10 after removal of the patch.

Number of animals:

3 males

Details on study design:

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: The test item was applied, as supplied, at a dose of 0.5 mL, on an undamaged skin area of the right flank of each animal.
- Type of wrap if used: The patch was secured in position with a strip of surgical adhesive tape.

REMOVAL OF TEST SUBSTANCE
- Time after start of exposure: 4 h

OBSERVATION TIME POINTS
- Skin reactions were appreciated 1 hour and then 24, 48, 72 hours and Days 4 to 10 after removal of the patch.

SCORING SYSTEM: According to OECD guideline 404

Irritation parameter:

erythema score

Basis:

animal #1

Remarks:

mean individual score

Time point:

24/48/72 h

Score:

1

Max. score:

4

Reversibility:

fully reversible within: 4 days

Remarks on result:

probability of weak irritation

Irritation parameter:

edema score

Basis:

animal #1

Remarks:

mean individual score

Time point:

24/48/72 h

Score:

0.3

Max. score:

4

Reversibility:

fully reversible within: 4 days

Remarks on result:

probability of weak irritation

Irritation parameter:

erythema score

Basis:

animal #2

Remarks:

mean individual score

Time point:

24/48/72 h

Score:

1.7

Max. score:

4

Reversibility:

fully reversible within: 10 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:

0.7

Max. score:

4

Reversibility:

fully reversible within: 10 days

Remarks on result:

probability of weak irritation

Irritation parameter:

erythema score

Basis:

animal #3

Remarks:

mean individual score

Time point:

24/48/72 h

Score:

2

Max. score:

4

Reversibility:

fully reversible within: 10 days

Remarks on result:

probability of mild irritation

Irritation parameter:

edema score

Basis:

animal #3

Remarks:

mean individual score

Time point:

24/48/72 h

Score:

0.3

Max. score:

4

Reversibility:

fully reversible within: 10 days

Remarks on result:

probability of weak irritation

Irritant / corrosive response data:

24 hours after the test item application, it was noted a well definite erythema, associated with a very slight oedema. The oedematous reactions were totally reversible between the 3rd and the 4th day of the test and the erythematous reactions were totally reversible between the 4th and the 7th day of the test.
On the cutaneous aspect, the skin recovered a normal aspect, between the 5th and the 11th day of the test.

Other effects:

None

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

Observations		Score
Skin reactions	Observation time	Animal no.A7286	Animal no.A7303	Animal no.A7304
Erythema and eschar	1 h	2	2	2
	24 h	2	2	2
	48 h	1	2	2
	72 h	0	1	2
	Day 4	0	0	2
	Day 5	-	0	1
	Day 6	-	0	0
	Day 7	-	0	0
	Day 8	-	0	0
	Day 9	-	0	0
	Day 10	-	0	0
	Mean (24, 48 and 72 h)	1.0	1.7	2.0
Oedema formation	1 h	1	1	1
	24 h	1	1	1
	48 h	0	1	0
	72 h	0	0	0
	Day 4	0	0	0
	Day 5	-	0	0
	Day 6	-	0	0
	Day 7	-	0	0
	Day 8	-	0	0
	Day 9	-	0	0
	Day 10	-	0	0
	Mean (24, 48 and 72 h)	0.3	0.7	0.3

Interpretation of results:

Category 3 (mild irritant) based on GHS criteria

Conclusions:

Under the test conditions, test substance is not classified as irritating to skin according to the criteria of the Regulation EC No. 1272/2008 (CLP) and classified in Category 3 (mild irritant) according to the GHS.

Executive summary:

In a dermal irritation study performed according to the OECD Guideline No. 404, and in compliance with GLP, undiluted test substance was applied at the dose of 0.5 mL, under semiocclusive dressing during 4 hours on an undamaged skin area of 3 rabbits. On the opposite flank an untreated area was served as the control. Skin irritation was assessed and scored according to the Draize scale at 1, 24, 48, 72 h and Days 4 to 10 after the 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.

 

24 hours after the test item application, it was noted a well definite erythema, associated with a very slight oedema. The oedematous reactions were totally reversible between the 3rd and the 4th day of the test and the erythematous reactions were totally reversible between the 4th and the 7th day of the test. On the cutaneous aspect, the skin recovered a normal aspect, between the 5th and the 11th day of the test.The individual scores for each animal within 3 scoring times (24, 48 and 72 h) were 1.0 / 1.7 / 2.0 for erythema and 0.3 / 0.7 / 0.3 for oedema. 

 

Under the test conditions, the test substance is not classified according to the criteria of the Regulation EC No. 1272/2008 (CLP) and classified in Category 3 (mild irritant) according to the 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:

20-30 April 2006

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

guideline study

Remarks:

GLP study conducted according to OECD Guideline 405 with deviations: age at study initiation, feeding conditions not reported. These deviations do not affect the quality of the study and are not considered to be relevant.

Qualifier:

according to guideline

Guideline:

OECD Guideline 405 (Acute Eye Irritation / Corrosion)

Version / remarks:

24 April 2002.

Deviations:

yes

Remarks:

age at study initiation, feeding conditions not reported

Qualifier:

according to guideline

Guideline:

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

Version / remarks:

Directive 2004/73/EC.

Deviations:

yes

Remarks:

age at study initiation, feeding conditions not reported

Principles of method if other than guideline:

Not applicable

GLP compliance:

yes (incl. QA statement)

Remarks:

Inspected on 2005-10-03 / Signed on 2005-12-13.

Specific details on test material used for the study:

- Test item was considered at 100% for the study.

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: 2.34-2.61 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: 19-23 °C
- Humidity: 38-61 %

IN-LIFE DATES: 20-30 April 2006

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 & Days 4, 5 and 6 following treatment, according to a numerical evaluation.

Number of animals or in vitro replicates:

3 males

Details on study design:

TREATMENT
A volume of 0.1 mL of the pure test item was instilled 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:

0.7

Max. score:

4

Reversibility:

fully reversible within: 48 h

Remarks on result:

probability of weak 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:

1.3

Max. score:

3

Reversibility:

fully reversible within: 5 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:

1

Max. score:

4

Reversibility:

fully reversible within: 72 h

Remarks on result:

probability of weak 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:

1

Max. score:

3

Reversibility:

fully reversible within: 72 h

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:

0.3

Max. score:

4

Reversibility:

fully reversible within: 48 h

Remarks on result:

probability of weak irritation

Irritation parameter:

cornea opacity score

Basis:

animal #3

Remarks:

mean individual score

Time point:

24/48/72 h

Score:

1.7

Max. score:

4

Reversibility:

fully reversible within: 6 days

Remarks on result:

probability of mild 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:

1.7

Max. score:

3

Reversibility:

fully reversible within: 4 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:

0.3

Max. score:

4

Reversibility:

fully reversible within: 48 h

Remarks on result:

probability of weak irritation

Irritant / corrosive response data:

The ocular reactions observed during the study have been moderate, and totally reversible in the three animals:
- at the conjunctivae level: a moderate redness, noted 1 hour after the test item instillation and totally reversible between the 4th and the 6th day of the test, associated with a moderate chemosis, noted 1 hour after the test item instillation and totally reversible between the 3rd and the 4th day of the test;
- at the corneal level: a moderate opacity, registered 24 hours after the test item instillation in two animals and totally reversible between the 3rd and the 7th day of the test.

Other effects:

None

Table 7.3.2/1: Individual and mean scores of conjunctivae, iris and cornea

Time / Animal	Cornea			Iris			Conjunctivae
							redness			chemosis
	1	2	3	1	2	3	1	2	3	1	2	3
1 h	0	0	0	0	0	0	2	2	2	2	2	2
24 h	2	0	2	0	0	0	2	2	2	2	1	1
48 h	0	0	2	0	0	0	1	1	2	1	0	0
72 h	0	0	1	0	0	0	1	0	1	0	0	0
D4	0	-	1	0	-	0	1	-	0	0	-	0
D5	0	-	1	0	-	0	0	-	0	0	-	0
D6	-	-	0	-	-	0	-	-	0	-	-	0
Total 24/48/72 h	2	0	5	0	0	0	4	3	5	3	1	1
Mean 24/48/72 h	0.7	0.0	1.7	0.0	0.0	0.0	1.3	1.0	1.7	1.0	0.3	0.3

Interpretation of results:

GHS criteria not met

Conclusions:

Under the test conditions, the test substance is not classified as irritating to eyes according to the criteria of the Regulation EC No. 1272/2008 (CLP) and of the GHS.

Executive summary:

In an eye irritation study conducted according to OECD 405 Guideline and in compliance with GLP, test substance was instilled as supplied, into the eye of 3 New Zealand rabbits at the dose of 0.1 mL, the other eye remained untreated serving as control. The lids were then gently held together for about one second in order to prevent loss of the test substance. The eyes were examined and the changes were observed at 1, 24, 48 and 72 h and 4, 5 and 6 days after treatment and graded according to the Draize method.  

 

The ocular reactions observed during the study have been moderate, and totally reversible in the three animals:

- at the conjunctivae level: a moderate redness, noted 1 hour after the test item instillation and totally reversible between the 4th and the 6th day of the test, associated with a moderate chemosis, noted 1 hour after the test item instillation and totally reversible between the 3rd and the 4th day of the test;

- at the corneal level: a moderate opacity, registered 24 hours after the test item instillation in two animals and totally reversible between the 3rd and the 7th day of the test.

 

Mean individual scores at 24, 48 and 72 h after exposure for the 3 animals were 0.7, 0.0, 1.7 for cornea score; 0.0, 0.0, 0.0 for iris score; 1.3, 1.0, 1.7 for conjunctivae score and 1.0, 0.3, 0.3 for chemosis score.

 

Under the test conditions, test substance is not classified as irritating to eyes according to the criteria of the Regulation EC No. 1272/2008 (CLP) and of the 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, 2006). 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. Initially, a single animal was treated. After consideration of the cutaneous responses produced in the first treated animal, two additional animals were treated.

24 hours after the test item application, it was noted a well definite erythema, associated with a very slight oedema. The oedematous reactions were totally reversible between the 3rd and the 4th day of the test and the erythematous reactions were totally reversible between the 4th and the 7th day of the test. On the cutaneous aspect, the skin recovered a normal aspect, between the 5th and the 11th day of the test.The individual scores for each animal within 3 scoring times (24, 48 and 72 h) were 1.0 / 1.7 / 2.0 for erythema and 0.3 / 0.7 / 0.3 for oedema. 

Eye irritation:

A key study was identified (Phycher, 2006). 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 lids were then gently held together for about one second in order to prevent loss of the test substance. The eyes were examined and the changes were observed at 1, 24, 48 and 72 h and 4, 5 and 6 days after treatment and graded according to the Draize method.

The calculated mean score for each animal within 3 scoring times (24, 48 and 72 h) were 0.7/0.0/1.7 for the corneal opacity, 0.0/0.0/0.0 for iridial inflammation, 1.3/1.0/1.7 for conjunctival redness and 1.0/0.3/0.3 for chemosis. The effects observed were all reversible within 7 days.

Justification for classification or non-classification

Harmonised classification:

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

Self classification:

Based on the available data:

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

- the substance is classified in Category 3 (mild irritant) for skin irritation according to the GHS.

- 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.