Acetic acid, 2-[(5-chloro-8-quinolinyl)oxy]-

Eye irritation

Administrative data

Endpoint:

eye irritation: in vivo

Type of information:

experimental study

Adequacy of study:

key study

Study period:

21 August 2013 - 04 October 2013

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

guideline study

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

2013

Report date:

2013

Materials and methods

Test guideline

Test guideline 1

Qualifier:

according to guideline

Guideline:

OECD Guideline 405 (Acute Eye Irritation / Corrosion)

Version / remarks:

October 2012

Deviations:

no

Test guideline 2

Qualifier:

according to guideline

Guideline:

EPA OPPTS 870.2400 (Acute Eye Irritation)

Version / remarks:

August 1998

Deviations:

no

Test guideline 3

Qualifier:

according to guideline

Guideline:

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

Version / remarks:

May 2008

Deviations:

no

Test guideline 4

Qualifier:

according to guideline

Guideline:

other: JMAFF 2-1-5

Version / remarks:

November 2000

Deviations:

no

GLP compliance:

yes (incl. QA statement)

Test material

Test material information

Constituent 1

Reference substance name:

[(5-chloroquinolin-8-yl)oxy]acetic acid

Cas Number:

88349-88-6

Molecular formula:

C11H8ClNO3

IUPAC Name:

[(5-chloroquinolin-8-yl)oxy]acetic acid

Test material form:

solid: particulate/powder

Remarks:

powder

Specific details on test material used for the study:

- Name of test material (as cited in study report): X204558
- Physical state: Tan solid
- Analytical purity: 98.3% ± 0.03% wt/wt
- Purity test date: 14 September 2014
- Lot/batch No.: 2GHB0002
- Storage condition of test material: in its original container at ambient condition

Test animals / tissue source

Species:

rabbit

Strain:

New Zealand White

Details on test animals or tissues and environmental conditions:

TEST ANIMALS
- Source: Animal Breeding Facility, Jai Research Foundation
- Age at study initiation: 15 to 16 weeks
- Weight at study initiation: 2.199 - 2.296 kg
- Housing: Individual stainless steel bottom rabbit cages with bedding material
- Diet ad libitum Teklad Certified Global High fiber rabbit pellet feed
- Water ad libitum UV sterilised drinking water filtered through Kent Reverse Osmosis
- Acclimation period: 7 days for rabbit N° 1 and 9 days for rabbit N° 2 and 3

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 19 to 23
- Humidity (%): 64 to 66
- Air changes (per hr): Minimum 15 air changes/hour
- Photoperiod (hrs dark / hrs light): 12 h artificial light and 12 h darkness

IN-LIFE DATES: From: 29 August 2013 To: 10 September 2013

Test system

Vehicle:

unchanged (no vehicle)

Controls:

yes, concurrent no treatment

Amount / concentration applied:

TEST MATERIAL
- Amount(s) applied (volume or weight with unit): 47.8, 48.9 and 48.1 mg (equivalent to 0.1 mL)

Duration of treatment / exposure:

1 hour

Observation period (in vivo):

The eyes of all rabbits were observed for signs of ocular irritation at 1, 24, 48 and 72 h

Number of animals or in vitro replicates:

Three females
Initially one rabbit was tested. Based on the observations at 24 hours post application, two additional rabbits were tested simultaneously to confirm the response.

Details on study design:

- Pre-treatment checks of the eyes were performed to confirm they were free of pre-existing irritation

REMOVAL OF TEST SUBSTANCE
- Washing (if done): The treated and the control eyes were gently washed with normal saline
- Time after start of exposure: at 1 h (to remove residual test item) and 24 h post-treatment

SCORING SYSTEM:
- Is presented in the tables below.

TOOL USED TO ASSESS SCORE: The treated and the control eyes of each rabbit were examined using fluorescein dye staining at 24 h post test item application.
One to two drops of fluorescein stain was instilled into the eye. The eye was washed using 0.9% normal saline to remove the residual stain from the eye and the eye was examined with the aid of Ophthalmoscope through a cobalt blue filter [disruption of corneal epithelium (% area) showing as green fluorescein staining] and any corneal damage was recorded post application.

Results and discussion

In vivo

Results

Results 1

Irritation parameter:

cornea opacity score

Basis:

mean

Time point:

24/48/72 h

Score:

0

Max. score:

4

Reversibility:

other: Not applicable/No effect

Results 2

Irritation parameter:

iris score

Basis:

mean

Time point:

24/48/72 h

Score:

0

Max. score:

2

Reversibility:

other: Not applicable/No effects

Results 3

Irritation parameter:

conjunctivae score

Remarks:

Redness

Basis:

mean

Time point:

24/48/72 h

Score:

1

Max. score:

3

Reversibility:

fully reversible within: 72 hours

Results 4

Irritation parameter:

chemosis score

Basis:

mean

Time point:

24/48/72 h

Score:

0.45

Max. score:

4

Reversibility:

fully reversible within: 72 hours

Irritant / corrosive response data:

Conjunctival effects were evident at 1, 24, 48 hours in all three rabbits and resolved by 72 hours after treatment. At the 1 hour post application time-point, the treated eye of all rabbits revealed conjunctival redness [score of 1] and conjunctival chemosis [score of 1]. The individual animal mean (n=3) eye irritation scores of 24, 48 and 72 hours post application observations were 0.00, 0.00, 0.00 for corneal opacity, 0.00, 0.00, 0.00 for iris effects, 1.00, 1.00, 1.00 for conjunctival redness and 0.67, 0.00, 0.67 for conjunctival chemosis for rabbit N° 1, 2 and 3, respectively. The test substance showed mild eye irritation which resolved by 72 h post application.

Other effects:

No signs of systemic toxicity including clinical observation and body weight were observed in the rabbits throughout the experimental period

Any other information on results incl. tables

Rabbit N°	Mean Score at 24, 48 and 72 Hours
	Corneal Opacity	Iris Lesion	Conjunctivae Redness	Conjunctivae Chemosis
1	0.00	0.00	1.00	0.67
2	0.00	0.00	1.00	0.00
3	0.00	0.00	1.00	0.67

Applicant's summary and conclusion

Interpretation of results:

GHS criteria not met

Remarks:

Migrated information Criteria used for interpretation of results: EU

Conclusions:

The test substance showed mild eye irritation which resolved by 72 hours post application, classification is not required.

Executive summary:

An acute eye irritation study was conducted in 3 adult female New Zealand White rabbits to assess the potential of X204558 (cloquintocet acid) to cause irritation or corrosion to the eye, according to OECD 405. A single ocular application of 0.1 mL of the test substance was administered to one eye of each the rabbits while the contralateral eye remained untreated and served as the control. Initially one rabbit was tested. Based on the results obtained at 24 hours post-application, the irritation response was confirmed by testing two additional rabbits simultaneously. Observations were made at 1, 24, 48 and 72 hours post application. Fluorescein dye staining was additionally carried out to evaluate corneal damage at 24 hours post application. General health status was also checked.

Conjunctival effects, consisting of mild redness (score of 1 or 2) and very slight chemosis (score of 1) were evident with recovery by 72 hours post-application. Examination with fluorescein dye and cobalt blue filter confirmed no corneal area damage at 24 hours in all rabbits. The control eyes did not show any abnormal reactions during the study. Moreover, there were no signs of systemic toxicity in any animal observed. The test substance caused a mild eye irritation which resolved by 72 hours post-test item application. The individual animal mean eye irritation scores at the 24, 48 and 72 h observation were 0.00, 0.00, 0.00 for corneal opacity, 0.00, 0.00, 0.00 for iris effects, 1.00, 1.00, 1.00 for conjunctival redness and 0.67, 0.00, 0.67 for conjunctival chemosis for rabbit N° 1, 2 and 3, respectively. Based on the results of this study, cloquintocet acid is not classified as an eye irritant according to the CLP Regulation.