Cyclopentaneacetic acid, 3-oxo-2-pentyl-, methyl ester, (1R,2S)-rel-

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:

key study

Study period:

From 02 May 2000 to 05 May 2000

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

other: see 'Remark'

Remarks:

OECD Guideline Study & Test in accordance with National procedures (OPPTS). 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 as data relates to a mixture of cis- and trans-isomers whereas the registered substance is the pure cis-isomer (see Iuclid section 13 for additional justification).

Cross-reference

Reason / purpose for cross-reference:

reference to same study

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

2000

Report date:

2000

Materials and methods

Test guideline

Test guideline 1

Qualifier:

according to guideline

Guideline:

OECD Guideline 405 (Acute Eye Irritation / Corrosion)

Deviations:

no

Test guideline 2

Qualifier:

according to guideline

Guideline:

EPA OPPTS 870.2400 (Acute Eye Irritation)

Deviations:

no

Principles of method if other than guideline:

Not applicable

GLP compliance:

yes

Test material

Test material information

Constituent 1

Reference substance name:

Methyl 3-oxo-2-pentylcyclopentaneacetate

EC Number:

246-495-9

EC Name:

Methyl 3-oxo-2-pentylcyclopentaneacetate

Cas Number:

24851-98-7

IUPAC Name:

methyl (3-oxo-2-pentylcyclopentyl)acetate

Test material form:

other: liquid

Details on test material:

- Substance type: pure active substance
- 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: Davidson's Mill Farm, South Brunswick, NJ - USA
- Age at study initiation: adult
- Weight at study initiation: not mentioned in study report
- Housing: suspended stainless steel caging with mesh floors which conform to the size recommendations in the most recent Guide for the Care and Use of Laboratory Animals DHEW (NlH). Litter paper was placed beneath the cage and was changed at least three times per week.
- Diet (e.g. ad libitum): Free access (Pelleted Purina Rabbit Chow #5326)
- Water (e.g. ad libitum): Free access (Filtered tap water was supplied by automatic water dispensing system)
- Acclimation period: six days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 17 to 23°C
- Humidity (%): 38 to 43%
- Air changes (per hr): not mentioned in the study report
- Photoperiod (hrs dark / hrs light): 12/12

IN-LIFE DATES: From: 02 May 2000 To: 05 May 2000

Test system

Vehicle:

unchanged (no vehicle)

Controls:

other: other eye (left eye)

Amount / concentration applied:

TEST MATERIAL
- Amount(s) applied (volume or weight with unit): 0.1 mL

Duration of treatment / exposure:

72 hours
(0.1 ml of the test substance, as received, was instilled into the conjunctival sac of the right eye of each rabbit by pulling the lower lid away from the eyeball. The upper and lower lids were then gently held together for about one second before releasing, to minimize loss of the test substance. The other eye of each rabbit remained untreated with the test substance and served as a control. The rabbits were then returned to their designated cages. Assessment of ocular damage/irritation was made approximately 1 hour and 24, 48 and 72 hours following treatment).

Observation period (in vivo):

Assessment of ocular damage/irritation was made approximately 1 hour and 24, 48 and 72 hours following treatment. An assessment of the initial pain reaction was made immediately after administration of the test material.

Number of animals or in vitro replicates:

3

Details on study design:

REMOVAL OF TEST SUBSTANCE
- Washing (if done): None
- Time after start of exposure: NA

SCORING SYSTEM: see "Attached background material"

TOOL USED TO ASSESS SCORE: Ocular irritation was evaluated using a high-intensity white light (Mag Lite) in accordance with Draize et al. at 1, 24, 48 and 72 hours post-instillation. The fluorescein dye evaluation procedure was used at 24 hours to verify the absence of corneal damage (see below). Individual scores were recorded for each animal. In addition to observations of the cornea, iris and conjunctivae, any other observed lesions were noted.
Prior to instillation, both eyes of a number of animals were examined using a fluorescein dye procedure. One drop of 2% ophthalmic fluorescein sodium was instilled into both eyes of each rabbit. The eyes were rinsed with physiological saline (0.9% NaCl) approximately 30 seconds after instillation of the fluorescein. Using a Blak-Ray® Lamp (compact 4-watt UV Lamp), the eyes were checked for gross abnormalities according to the "Scale for Scoring Ocular Lesions". Only healthy animals without pre-existing ocular irritation were selected for test.

Results and discussion

In vivo

Results

Results 1

Irritation parameter:

cornea opacity score

Basis:

animal: #1, #2 and #3

Time point:

other: mean 24, 48 and 72 hours

Score:

0

Max. score:

4

Results 2

Irritation parameter:

iris score

Basis:

animal: #1, #2 and #3

Time point:

other: mean 24, 48 and 72 hours

Score:

0

Max. score:

2

Results 3

Irritation parameter:

conjunctivae score

Basis:

animal #1

Time point:

other: mean 24, 48 and 72 hours

Score:

0

Max. score:

3

Results 4

Irritation parameter:

conjunctivae score

Basis:

animal: #2 and #3

Time point:

other: mean 24, 48 and 72 hours

Score:

0.33

Max. score:

3

Reversibility:

fully reversible within: 48 hours

Results 5

Irritation parameter:

chemosis score

Basis:

animal: #1, #2 & #3

Time point:

other: mean 24, 48 and 72 hours

Score:

0

Max. score:

4

Irritant / corrosive response data:

See above block of fields "Overall Irritation/corrosion results"

Other effects:

None.
All animals appeared active and healthy. Apart from the eye irritation noted below, there were no other signs of gross toxicity, adverse pharmacologic effects or abnormal behaviour. No corneal opacity or iritis was noted during the study. One hour after test substance instillation, all three treated eyes exhibited conjunctivitis. The incidence and severity of irritation decreased with time. All animals were free of ocular irritation within 48 hours.

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)	Discharge (/3)
1 h	0 / 0 / 0	0 / 0 / 0	1 / 2 / 2	0 / 1 / 1	E
24 h	0 / 0 / 0	0 / 0 / 0	0 / 1 / 1	0 / 0 / 0	0 / 0 / 0
48 h	0 / 0 / 0	0 / 0 / 0	0 / 0 / 0	0 / 0 / 0	0 / 0 / 0
72 h	0 / 0 / 0	0 / 0 / 0	0 / 0 / 0	0 / 0 / 0	0 / 0 / 0
Average 24h, 48h, 72h	0 / 0 / 0	0 / 0 / 0	0.0 / 0.33 / 0.33	0.0 / 0.0 / 0.0	0 / 0 / 0
Reversibility*)	-	-	c.	c.	-
Average time for reversion	-	-	48 h	-	-

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

 E = scoring masked by residual test substance

All treated eyes appeared normal at the 72-hour observation.

Applicant's summary and conclusion

Interpretation of results:

not irritating

Remarks:

Migrated information Criteria used for interpretation of results: EU

Conclusions:

The individual score for each individual lesion for each animal within 3 scoring times (24, 48 and 72 hrs) were 0.00/0.33/0.33 for erythema, and 0.00/0.00/0.00 for chemosis, discharge, iris lesions and corneal opacity. Under the test conditions, the test material is not classified as irritating to eyes.

Executive summary:

The study was performed to assess the irritancy potential of the test material to the eye of the New Zealand White rabbit. The method was designed to meet the requirements of the OECD Guideline No. 405 “Acute Eye Irritation/Corrosion” (2002) and of the Health Effects Test Guidelines, OPPTS 870.2400 (1998).

0.1 mL of the test substance, as received, was instilled into the right eye of three healthy rabbits. The left eye remained untreated and served as a control. Ocular irritation was evaluated by the method of Draize. No corneal opacity or iritis was noted during the study. One hour after test substance instillation, all three treated eyes exhibited conjunctivitis. The incidence and severity of irritation decreased with time. All animals were free of ocular irritation within 48 hours.

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

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 as data relates to a mixture of cis- and trans-isomers whereas the registered substance is the pure cis-isomer (see Iuclid section 13 for additional justification).