4-methyl-2-(pentan-3-yl)tetrahydro-2H-pyran-4-ol

Endpoint summary

Description of key information

Skin irritation: not irritating (OECD 404, GLP, K, Rel.2)

Eye irritation: irritating (OECD 405, GLP, 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:

18-28 March 2008

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

guideline study

Remarks:

GLP study conducted according to OECD 404 Guideline without any deviation. However, isomers ratio is not reported.

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:

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 2007-01-11 / Signed on 2007-02-21.

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)
- Age at study initiation: 11-12 weeks
- Weight at study initiation: 2.36-2.85 kg
- Housing: Each animal was kept in an individual box installed in conventional air conditioned animal husbanding.
- Diet: Foodstuff (SDS –C15), ad libitum
- Water: Drinking water (tap-water from public distribution system), ad libitum
- Acclimation period: 5 days

ENVIRONMENTAL CONDITIONS
- Temperature: 19-22 °C
- Humidity: 39-68 %
- Air changes: at least ten changes per hour
- Photoperiod: 12 h dark / 12 h light

IN-LIFE DATES: 18-28 March 2008

Type of coverage:

semiocclusive

Preparation of test site:

clipped

Vehicle:

unchanged (no vehicle)

Controls:

other: On the opposite flank an untreated area was used 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:

Skin reactions were appreciated 1, 24, 48 and 72 h after removal of the patch.

Number of animals:

3 males

Details on study design:

TEST SITE
- Area of exposure: Approximately 24 h before the test, the rabbit’s back and flanks were shorn using electric clippers equipped with a fine comb, so as to expose an area of skin about 6 cm2 per patch.
- As no tissue destruction was noted after a treatment during 3 minutes and 1 hour, the test item was applied, as supplied, at a dose of 0.5 mL, on an undamaged skin area of one flank of each animal, during 4 hours.
- Type of wrap if used: The patch was secured in position with a strip of surgical adhesive tape under semiocclusive dressing.
- Initially, a single animal was treated. After consideration of the cutaneous responses produced in the first treated animal, two additional animals were treated during 4 hours.

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

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:

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

Max. score:

4

Reversibility:

fully reversible within: 24 h

Remarks on result:

no indication of 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:

fully reversible within: 24 h

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:

A very slight erythema was noted, in two animals, only at the reading time 1 hour.

Other effects:

None

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

Observations		Score
Skin reactions	Observation time	Animal no. A8862	Animal no. A8876	Animal no. A8877
Erythema and eschar	1 h (D0)	0	1	1
	24 h	0	0	0
	48 h	0	0	0
	72 h	0	0	0
	Mean (24, 48 and 72 h)	0.0	0.0	0.0
Oedema formation	1 h (D0)	0	0	0
	24 h	0	0	0
	48 h	0	0	0
	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 the test conditions, the test substance is not classified as irritatng to skin according to the criteria 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 the shorn skin of the flanks of 3 male New Zealand White rabbits. On the opposite 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 h 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 during 4 hours.

 

A very slight erythema was noted, in two animals, only at the reading time 1 hour. The individual scores for each animal within 3 scoring times (24, 48 and 72 h) were 0.0 / 0.0 / 0.0 for erythema and 0.0 / 0.0 / 0.0 for oedema.

Under the test conditions, test substance is not classified according to the criteria 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:

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:

25 March to 11 April 2008

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

guideline study

Remarks:

GLP study conducted according to OECD 405 Guideline without any deviation. However, the isomers ratio is not reported.

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 2007-01-11 / Signed on 2007-02-21.

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)
- Age at study initiation: 12-13 weeks
- Weight at study initiation: 2.73-3.11 kg
- Housing: Each animal was kept in an individual box installed in conventional air conditioned animal husbanding.
- Diet: Foodstuff (SDS- C15), ad libitum
- Water: Drinking water (tap-water from public distribution system), ad libitum
- Acclimation period: 5 days

ENVIRONMENTAL CONDITIONS
- Temperature: 19–23 °C
- Humidity: 42-60 %
- Air changes: at least ten changes per hour
- Photoperiod: 12 h dark / 12 h light

IN-LIFE DATES: 25 March to 11 April 2008

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 to 21 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:

2

Max. score:

4

Reversibility:

fully reversible within: 9 days

Remarks on result:

positive indication of irritation

Irritation parameter:

iris score

Basis:

animal #1

Remarks:

mean individual score

Time point:

24/48/72 h

Score:

0.3

Max. score:

2

Reversibility:

fully reversible within: 48 h

Remarks on result:

probability of weak 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: 8 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:

0.7

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:

2

Max. score:

4

Reversibility:

fully reversible within: 7 days

Remarks on result:

positive 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:

1.3

Max. score:

3

Reversibility:

fully reversible within: 6 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:

1.3

Max. score:

4

Reversibility:

fully reversible within: 5 days

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: 11 days

Remarks on result:

probability of weak 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:

1.3

Max. score:

3

Reversibility:

fully reversible within: 6 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:

1.3

Max. score:

4

Reversibility:

fully reversible within: 4 days

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 D6 and D8, associated with a moderate chemosis, noted 1 hour after the test item instillation and totally reversible between D3 and D5;
- at the corneal level: a moderate opacity, registered 24 hours after the test item instillation and totally reversible between D7 and D11,
- at the iris level: a congestion only noted 24 hours after the test item instillation in one animal.

Other effects:

None

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

Time / Animal No.	Cornea			Iris			Conjunctivae
							redness			chemosis
	#1	#2	#3	#1	#2	#3	#1	#2	#3	#1	#2	#3
24h	2	2	2	1	0	0	2	2	2	1	2	2
48h	2	2	2	0	0	0	1	1	1	1	1	1
72h	2	2	1	0	0	0	1	1	1	0	1	1
Day 4		2	1		0	0		1	1		1	0
Day 5		1	1		0	0		1	1		0	0
Day 6	1	1	1	0	0	0	1	0	0	0	0	0
Day 7	1	0	1	0	0	0	1	0	0	0	0	0
Day 8	1		1	0		0	0		0	0		0
Day 9	0		1	0		0	0		0	0		0
Day 10			1			0			0			0
Day 11			0			0			0			0
Mean 24/48/72h	2.0	2.0	1.7	0.3	0.0	0.0	1.3	1.3	1.3	0.7	1.3	1.3

#1:A8893; #2:A8894; #3:A8895

Interpretation of results:

Category 2A (irritating to eyes) based on GHS criteria

Conclusions:

Under the test conditions, the test substance is classified for eye irritation in Category 2 (H319: Causes severe eye irritation) according to the Regulation (EC) No. 1272/2008 (CLP) and in Category 2A "irritating to eyes" according to the GHS.

Executive summary:

In an eye irritation study conducted according to OECD 405/EU Method B.5 guidelines and in compliance with GLP, 3 New Zealand White female rabbits were exposed to 0.1 mL of test substance in one eye while the contralateral 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 item. The eyes were examined and the changes were observed at 1, 24, 48 and 72 h and Days 4 to 11 following 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 D6 and D8, associated with a moderate chemosis, noted 1 hour after the test item instillation and totally reversible between D3 and D5;

- at the corneal level: a moderate opacity, registered 24 hours after the test item instillation and totally reversible between D7 and D11,

- at the iris level: a congestion only noted 24 hours after the test item instillation in one animal. 

Mean individual scores at 24, 48 and 72 h after exposure for the 3 animals were 2.0, 2.0, 1.7 for cornea score; 0.3, 0.0, 0.0 for iris score; 1.3, 1.3, 1.3 for conjunctivae score and 0.7, 1.3, 1.3 for chemosis score.

Under the test conditions, test substance is classified for eye irritation in Category 2 (H319: Causes severe eye irritation) according to the Regulation (EC) No. 1272/2008 (CLP) and in Category 2A "irritating to eyes" according to the GHS.

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

Endpoint conclusion

Endpoint conclusion:

adverse effect observed (irritating)

Respiratory irritation

Endpoint conclusion

Endpoint conclusion:

no study available

Additional information

Skin irritation:

A key study was identified (Phycher, 2008, Re.2). 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.

A very slight erythema was noted, in two animals, only at the reading time 1 hour. The individual scores for each animal within 3 scoring times (24, 48 and 72 h) were 0.0 / 0.0 / 0.0 for erythema and 0.0 / 0.0 / 0.0 for oedema. The substance is therefore not classified for skin irritation.

Eye irritation:

A key study was identified (Phycher, 2008, Rel.2). 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 Days 4 to 11 following 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 2.0, 2.0, 1.7 for cornea score; 0.3, 0.0, 0.0 for iris score; 1.3, 1.3, 1.3 for conjunctivae score and 0.7, 1.3, 1.3 for chemosis score. The effects observed were all reversible within 11 days. The substance is therefore classified as "Category 2A irritating to eyes".

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:

Skin irritation:

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

Eye irritation:

Based on the available data, the substance should be classified as eye irritation Category 2 (H319: Causes serious eye irritation) according to the CLP and as Category 2A "irritating to eyes" according to the GHS.

Respiratory irritation:

No data was available regarding respiratory irritation.