Pentadecan-15-olide

Eye irritation

Administrative data

Endpoint:

eye irritation: in vivo

Type of information:

migrated information: read-across from supporting substance (structural analogue or surrogate)

Adequacy of study:

weight of evidence

Study period:

From 2004-10-04 to 2004-10-24

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

other: see 'Remark'

Remarks:

Study performed according to OECD test guideline No. 405 and in compliance with GLP. The study was fully reliable (Klimisch score = 1), however the reliability score was lowered to 2 which is the maximum score for read-across. The supporting substance is considered adequate for read-across purpose (see Iuclid section 13 for justification).

Cross-reference

Cross-reference 1

Reason / purpose for cross-reference:

reference to same study

Cross-reference 2

Reason / purpose for cross-reference:

reference to other study

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

2004

Report date:

2004

Materials and methods

Test guideline

Test guideline 1

Qualifier:

according to guideline

Guideline:

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

Deviations:

no

Test guideline 2

Qualifier:

according to guideline

Guideline:

OECD Guideline 405 (Acute Eye Irritation / Corrosion)

Version / remarks:

adopted 2002-04-24

Deviations:

no

Principles of method if other than guideline:

not applicable

GLP compliance:

yes (incl. QA statement)

Remarks:

signed 2000-08-02

Test material

Test material information

Constituent 1

Reference substance name:

A mixture of: (E)-oxacyclohexadec-12-en-2-one; (E)-oxacyclohexadec-13-en-2-one; a) (Z)-oxacyclohexadec-(12)-en-2-one and b) (Z)-oxacyclohexadec-(13)-en-2-one

EC Number:

422-320-3

EC Name:

A mixture of: (E)-oxacyclohexadec-12-en-2-one; (E)-oxacyclohexadec-13-en-2-one; a) (Z)-oxacyclohexadec-(12)-en-2-one and b) (Z)-oxacyclohexadec-(13)-en-2-one

IUPAC Name:

422-320-3

Test material form:

other: liquid

Details on test material:

- Chemical name: E/Z-Oxacyclohexadec-12/13-en-2-one
- Physical state: clear, colourless to light yellow liquid
- Storage condition of test material: cool, in full tightly closed containers, in a dark place

Test animals / tissue source

Species:

rabbit

Strain:

Himalayan

Details on test animals or tissues and environmental conditions:

TEST ANIMALS
- Source: LPT Laboratory of Pharmacology and Toxicology KG, branch Löhndorf, 24601 Löhndorf/Post Wankendorf, Germany
- Age at dosing: approx. 4.5 - 5.5 months
- Weight at study initiation: 2.2 kg to 2.7 kg
- Housing: during the acclimatisation period and after the 8-hour period in restrainers, the animals were kept singly in cages with dimensions of 400 mm X 500 mm X 370 mm (manufacturer: Dipl. Ing. W. EHRET GmbH, 16352 Schönenwalde, Germany); for 8 hours following test item application, the animals were kept singly in restrainers which allowed free movement of the head but prevented a complete body turn, wiping of the eyes with the paws and excluded irritation of the eye by excrements and urine.
- Diet (ad libitum before and after the exposure period): ssniff® K-H V2333 (ssniff Spezialdiäten GmbH, 59494 Soest, Germany)
- Water (ad libitum before and after the exposure period): tap water
- Acclimation period: at least 20 adaptation days

ENVIRONMENTAL CONDITIONS
- Temperature: 20 °C +/- 3 °C (maximum range)
- Relative humidity: 30 % - 70 % (maximum range)
- Photoperiod (hrs dark / hrs light): 12/12

Test system

Vehicle:

unchanged (no vehicle)

Controls:

other: left eye served as control

Amount / concentration applied:

TEST MATERIAL
- Amount(s) applied (volume or weight with unit): 0.1 mL of the test item was administered per eye (single instillation).
The test item was placed into the conjunctival sac of the right eye of each animal after gently pulling the lower lid away from the eyeball. The lids were then gently held together for about one second in order to prevent loss of the material. The left eye, which remained untreated, served as a control.

Duration of treatment / exposure:

not applicable

Observation period (in vivo):

1, 24, 48 and 72 hours after the administration.

Number of animals or in vitro replicates:

3 male rabbits

Details on study design:

SCORING SYSTEM: according to the Draize scale
Any further lesions are listed.

TOOL USED TO ASSESS SCORE: the eyes were examined ophthalmoscopically with a slit lamp prior to the administration and 1, 24, 48 and 72 hours after the administration. The eye reactions were observed and registered.
24 hours after administration the eyes were treated additionally with fluorescein (Fluorescein SE Thilo drops (ALCON PHARMA GmbH, D-79108 Freiburg) and examined.

OBSERVATIONS:
General criteria: body weight of all animals was measured at the beginning of the study. Behaviour and food consumption were monitored.

Results and discussion

In vivo

Results

Results 1

Irritation parameter:

cornea opacity score

Basis:

mean

Remarks:

animal #1, #2 & #3

Time point:

other: mean 24, 48 and 72 hours

Score:

0

Max. score:

4

Results 2

Irritation parameter:

iris score

Basis:

mean

Remarks:

animal #1, #2 & #3

Time point:

other: mean 24, 48 and 72 hours

Score:

0

Max. score:

2

Results 3

Irritation parameter:

conjunctivae score

Basis:

mean

Remarks:

animal #1 & #3

Time point:

other: mean 24, 48 and 72 hours

Score:

0

Max. score:

3

Results 4

Irritation parameter:

chemosis score

Basis:

mean

Remarks:

animal #1, #2 & #3

Time point:

other: mean 24, 48 and 72 hours

Score:

0

Max. score:

4

Results 5

Irritation parameter:

conjunctivae score

Basis:

mean

Remarks:

animal #2

Time point:

other: mean 24, 48 and 72 hours

Score:

0.33

Max. score:

3

Reversibility:

fully reversible within: 48 hours

Irritant / corrosive response data:

Conjunctival redness (grade 1) was observed in all animals 1 hour after instillation, in one animal until 24 hours after instillation.
In addition, secretion was observed in two animals 1 hour after instillation. Chemosis was not observed during the observation period.
The cornea and iris were not affected by instillation of the test item.
The 24-hour fluorescein test: no pathological findings.

Other effects:

There were no systemic intolerance reactions.

Any other information on results incl. tables

Table 7.3.2/1: Irritant/corrosive response data each animals at each observation time up to removal from the test

 

Score at time point / Reversibility	Cornea	Iris (/2)	Conjunctivae
	Opacity (/4)		Redness (/3)	Chemosis (/4)
1 h	0 / 0 / 0	0 / 0 / 0	1 / 1 / 1	0 / 0* / 0*
24 h	0 / 0 / 0	0 / 0 / 0	0 / 1 / 0	0 / 0 / 0
48 h	0 / 0 / 0	0 / 0 / 0	1 / 1 / 1	0 / 0 / 0
72 h	0 / 0 / 0	0 / 0 / 0	0 / 0 / 0	0 / 0 / 0
Average 24h, 48h, 72h	0 / 0 / 0	0 / 0 / 0	0 / 0.33 / 0	0 / 0 / 0
Reversibility*)	-	-	c.	c.
Average time (unit) for reversion	-	-	48 h	72 h

*) Reversibility: c. = completely reversible; n.c. = not completely reversible; n. = not reversible

* secretion

Applicant's summary and conclusion

Interpretation of results:

not irritating

Remarks:

Migrated information Criteria used for interpretation of results: EU

Conclusions:

Under the test conditions, the test material is not classified as irritating to eyes according to the criteria of the Annex VI of the Regulation (EC) No. 1272/2008 (CLP) and of the Directive 67/548/EEC.

Executive summary:

In an eye irritation study performed according to the OECD test guideline No. 405, and in compliance with GLP, 0.1 mL of undiluted test material was instilled into the right eye of 3 male Himalayan rabbit. The eyes were not rinsed after the instillation of the test item. The left eye of each rabbit served as control. Animals were observed at 1, 24, 48 and 72 hours after dosing under a standard light source. 24 hours after administration the eyes were treated additionally with fluorescein and examined. The reactions in the conjunctiva (redness, chemosis and discharge), the iris and the cornea (opacity and area involved) were scored according to the Draize scale. 

Conjunctival redness (grade 1) was observed in all animals 1 hour after instillation, in one animal until 24 hours after instillation. In addition, secretion was observed in two animals 1 hour after instillation. Chemosis was not observed during the observation period. The cornea and iris were not affected by instillation of the test item.

The calculated mean score for each individual lesion for each animal within 3 scoring times (24, 48 and 72 h) were 0.00 / 0.33 /0.00 for redness, and 0.00 / 0.00 /0.00 for chemosis, discharge, iris and corneal lesions.

 

Under the test conditions, the test material is not classified as irritating to eyes according to the criteria of the Annex VI of the Regulation (EC) No. 1272/2008 (CLP) and of the Directive 67/548/EEC.

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

The supporting substance is considered adequate for read-across purpose (see Iuclid section 13 for justification).