2H-Pyran-2-one, tetrahydro-5-pentyl-

Eye irritation

Administrative data

Endpoint:

eye irritation: in vivo

Type of information:

experimental study

Adequacy of study:

key study

Study period:

Between 21 and 25 November 2005.

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

guideline study

Remarks:

GLP study conducted in compliance with OECD Guideline No. 405 with deviations not affecting the reliability of the study: details on feeding and environmental conditions not reported.

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

2005

Report date:

2005

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:

yes

Remarks:

details on feeding and environmental conditions not reported.

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:

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.

Test material

Test material information

Constituent 1

Reference substance name:

(5R)-5-pentyloxan-2-one

Molecular formula:

C10 H18 O2

IUPAC Name:

(5R)-5-pentyloxan-2-one

Constituent 2

Reference substance name:

(5S)-5-pentyloxan-2-one

Molecular formula:

C10 H18 O2

IUPAC Name:

(5S)-5-pentyloxan-2-one

Test material form:

liquid

Details on test material:

- Physical state: Liquid
- Storage condition of test material: room temperature.

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).
- Weight at study initiation: 2.25 - 3.24 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: 18-23 °C
- Humidity: 26-43 %. A relative humidity of 26% was registered instead of 30% (minimal limit) as planned in the experimental protocol. This deviation did not, in any case, influence the development and the results of the study.
- Air changes: no data.
- Photoperiod: no data.

IN-LIFE DATES: from 21 to 25 November, 2005.

Test system

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 & Day 4 following treatment, according to a numerical evaluation.

Number of animals or in vitro replicates:

3 males

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:

0

Max. score:

4

Reversibility:

other: not applicable

Remarks on result:

no indication of irritation

Results 2

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

Results 3

Irritation parameter:

conjunctivae score

Basis:

animal #1

Remarks:

mean individual score

Time point:

24/48/72 h

Score:

1

Max. score:

3

Reversibility:

fully reversible within: 4 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:

0.3

Max. score:

4

Reversibility:

fully reversible within: 2 days

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:

0

Max. score:

4

Reversibility:

other: not applicable.

Remarks on result:

no 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:

0.7

Max. score:

3

Reversibility:

fully reversible within: 3 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:

0

Max. score:

4

Reversibility:

other: not applicable.

Remarks on result:

no indication of irritation

Results 9

Irritation parameter:

cornea opacity score

Basis:

animal #3

Remarks:

mean individual score

Time point:

24/48/72 h

Score:

1

Max. score:

4

Reversibility:

fully reversible within: 3 days

Remarks on result:

probability of mild 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:

0.3

Max. score:

3

Reversibility:

fully reversible within: 2 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:

0

Max. score:

4

Reversibility:

other: not applicable.

Remarks on result:

no indication of irritation

Irritant / corrosive response data:

The ocular reactions observed during the study have been slight to moderate, and totally reversible in the three animals:
- at the conjunctivae level: a slight redness, noted 1 hour after the test item instillation and totally reversible between the 3rd and the 5th day of the test, associated with a slight to moderate chemosis, noted 1 hour after the test item instillation and totally reversible between the 2nd and the 3rd day of the test ;
- at the corneal level: a moderate opacity, registered 24 hours after the test item instillation, in only one animal, and totally reversible the 4th day of the test.

Other effects:

None

Any other information on results incl. tables

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
A 6986 Male	1 h	0	0	1	1
	24 h	0	0	1	1
	48 h	0	0	1	0
	72 h	0	0	1	0
	Day 4	0	0	0	0
	Total (24, 48 and 72 h)	0	0	3	1
	Mean (24, 48 and 72 h)	0	0	1	0.3

Rabbit Number and Sex	Time After Treatment	Corneal Opacity	Iris lesion	Conjunctival Redness	Conjunctival Chemosis
A7020 Male	1 h	0	0	1	1
	24 h	0	0	1	0
	48 h	0	0	1	0
	72 h	0	0	0	0
	Day 4	0	0	0	0
	Total (24, 48 and 72 h)	0	0	2	0
	Mean (24, 48 and 72 h)	0	0	0.7	0

Rabbit Number and Sex	Time After Treatment	Corneal Opacity	Iris lesion	Conjunctival Redness	Conjunctival Chemosis
A 7021 Male	1 h	0	0	1	2
	24 h	2	0	1	0
	48 h	1	0	0	0
	72 h	0	0	0	0
	Day 4	0	0	0	0
	Total (24, 48 and 72 h)	3	0	0	0
	Mean (24, 48 and 72 h)	1	0	0.3	0

Applicant's summary and conclusion

Interpretation of results:

GHS criteria not met

Conclusions:

Under the test conditions, the test material is not classified as irritating to eyes according to 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, 3 New Zealand White male 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 and day 4 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.

A slight redness noted 1 hour after the test item instillation and totally reversible between the 3rd and the 5th day of the test, associated with a slight to moderate chemosis, noted 1 hour after the test item instillation and totally reversible between the 2nd and the 3rd day of the test. At the corneal level, a moderate opacity, registered 24 hours after the test item instillation, in only one animal, and totally reversible the 4th day of the test.

 

Mean individual scores at 24, 48 and 72 h after exposure for the 3 animals were 0.0, 0.0, 1.0 for cornea score; 0.0, 0.0, 0.0 for iris score; 1.0, 0.7, 0.3 for conjunctivae score and 0.3, 0.0, 0.0 for chemosis score. These effects are reversible between days 2 and 4.

 

Under the test conditions, the test material is not classified as irritating to eyes according to 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.