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

Skin irritation / corrosion

Administrative data

Endpoint:

skin 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 404 (Acute Dermal Irritation / Corrosion)

Version / remarks:

April 2002

Deviations:

no

Test guideline 2

Qualifier:

according to guideline

Guideline:

EPA OPPTS 870.2500 (Acute Dermal Irritation)

Version / remarks:

August 1998

Deviations:

no

Test guideline 3

Qualifier:

according to guideline

Guideline:

EU Method B.4 (Acute Toxicity: Dermal Irritation / Corrosion)

Version / remarks:

May 2008

Deviations:

no

Test guideline 4

Qualifier:

according to guideline

Guideline:

other: JMAFF 2-1-4

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

Species:

rabbit

Strain:

New Zealand White

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Source: Animal Breeding Facility, Jai Research Foundation
- Age at study initiation: 15 to 16 weeks
- Weight at study initiation: 2.269 - 2.449 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: 6 days (rabbit N° 1) and 8 days (rabbits 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: 09 September 2013

Test system

Type of coverage:

semiocclusive

Preparation of test site:

clipped

Vehicle:

water

Controls:

yes, concurrent vehicle

Amount / concentration applied:

TEST MATERIAL
- Amount(s) applied (volume or weight with unit): 500 mg moistened with 0.5 mL distilled water

Duration of treatment / exposure:

4 hour exposure period

Observation period:

Skin reactions were observed at 1, 24, 48 and 72 hours post-patch removal

Number of animals:

Three males.
Initially one rabbit was tested. Based on the observations at 24 hour post-patch removal, two additional rabbits were tested simultaneously to confirm the irritation response.

Details on study design:

TEST SITE
- Area of exposure: 6 cm2 body surface area. Approximately 24 hours prior to the treatment, hair from the dorso-lumbar region at two contra-lateral sites of each rabbit was closely clipped using a clipper. Care was taken to ensure that the skin was not abraded while clipping.
- Type of wrap if used: covered with gauze patches of approximately 6 cm2 (gauze rolled) which were not more than 8-ply and were secured at the margins by non-irritating tape

REMOVAL OF TEST SUBSTANCE
- Washing (if done): test item was removed with cotton soaked in distilled water
- Time after start of exposure: At the end of the 4 hour exposure period

SCORING SYSTEM:
- Is outlined in the tables below.

Results and discussion

In vivo

Results

Results 1

Irritation parameter:

erythema score

Basis:

mean

Time point:

24/48/72 h

Score:

0.22

Max. score:

4

Reversibility:

fully reversible within: 48 hours

Results 2

Irritation parameter:

edema score

Basis:

mean

Time point:

24/48/72 h

Score:

0

Max. score:

4

Reversibility:

other: Not applicable/No effect

Irritant / corrosive response data:

At 1 h post-patch removal, the treated skin site of all rabbits revealed very slight erythema (score of 1).
The mean scores of erythema (0.00 to 0.33) and oedema (0.00) observed for the 24, 48 and 72 hours observation time-points indicated that the test item is a non-irritant under the described experimental conditions.

Other effects:

No clinical signs were observed in any rabbit throughout the experimental period

Any other information on results incl. tables

Rabbit N°	Site of Application	Observations after Patch Removal
		Erythema				Oedema
		Hours				Hours
		1	24	48	72	1	24	48	72
1	Right	1	0	0	0	0	0	0	0
2	Right	1	1	0	0	0	0	0	0
3	Right	1	1	0	0	0	0	0	0

Applicant's summary and conclusion

Interpretation of results:

GHS criteria not met

Conclusions:

The mean scores of erythema and oedema observed for the 24-72 hour observation period indicated that the test item is not irritating to skin and classification is not required.

Executive summary:

An acute dermal irritation study was conducted in three adult male New Zealand White rabbits to assess the potential of X204558 (cloquintocet acid) to cause skin irritation or corrosion, according to OECD 404. The test substance (500 mg) was moistened with 50 ml of distilled water and applied to the treatment skin sites, with a surface of approximately 6 cm². The contra-lateral control skin sites were similarly treated with 0.5 mL distilled water. The treated and the control sites were covered with a semi-occlusive dressing left in place for a 4 hour exposure period, at the end of which, the residual test item was removed with cotton soaked in distilled water. The skin reactions were observed at 1, 24, 48, and 72 hours post-patch removal. Irritation was scored and general health conditions were monitored. Initially one rabbit was tested. Based on the observations at 24 hour post-patch removal, two additional rabbits were tested simultaneously to confirm the irritation response.

At the treated sites, very slight erythema (score of 1) was observed at the 1 hour time-point after patch removal. This effect was reversed by the 24 hour time-point in the first rabbit, and was reversed by the 48 hour time-point in the remaining rabbits. There were no reactions recorded at the control sites throughout the study. There were no signs of systemic adverse effects in any of the treated animals. The test substance caused a mild and transient local reaction to the treated skin. The mean dermal irritation scores at 24, 48 and 72 hours post-patch removal for individual animals were 0.00, 0.33, 0.33 for erythema and 0.00, 0.00, 0.00 for oedema. Based on the results of this study, cloquintocet acid is not classified as a skin irritant according to the CLP Regulation.