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

Eye irritation

Administrative data

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.

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

2008

Report date:

2008

Materials and methods

Test guideline

Test guideline 1

Qualifier:

according to guideline

Guideline:

OECD Guideline 405 (Acute Eye Irritation / Corrosion)

Version / remarks:

24 April 2002

Deviations:

no

Test guideline 2

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.

Test material

Test material information

Constituent 1

Reference substance name:

Reaction mass of (2R,4R)-4-methyl-2-(pentan-3-yl)tetrahydro-2H-pyran-4-ol & (2S,4S)-4-methyl-2-(pentan-3-yl)tetrahydro-2H-pyran-4-ol

Molecular formula:

C11H22O2

IUPAC Name:

Reaction mass of (2R,4R)-4-methyl-2-(pentan-3-yl)tetrahydro-2H-pyran-4-ol & (2S,4S)-4-methyl-2-(pentan-3-yl)tetrahydro-2H-pyran-4-ol

Constituent 2

Reference substance name:

Reaction mass of (2S,4R)-4-methyl-2-(pentan-3-yl)tetrahydro-2H-pyran-4-ol & (2R,4S)-4-methyl-2-(pentan-3-yl)tetrahydro-2H-pyran-4-ol

Molecular formula:

C11H22O2

IUPAC Name:

Reaction mass of (2S,4R)-4-methyl-2-(pentan-3-yl)tetrahydro-2H-pyran-4-ol & (2R,4S)-4-methyl-2-(pentan-3-yl)tetrahydro-2H-pyran-4-ol

Test material form:

liquid

Details on test material:

- Physical state: Colourless to pale yellow, limpid/translucent liquid

Specific details on test material used for the study:

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

Test animals / tissue source

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

Test system

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

Results and discussion

In vivo

Results

Results 1

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

Results 2

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

Results 3

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

Results 4

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

Results 5

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

Results 6

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

Results 7

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

Results 8

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

Results 9

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

Results 10

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

Results 11

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

Results 12

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

Any other information on results incl. tables

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

Applicant's summary and conclusion

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.