Phenylacetic acid

Eye irritation

Administrative data

Endpoint:

eye irritation: in vivo

Type of information:

experimental study

Adequacy of study:

key study

Reliability:

4 (not assignable)

Rationale for reliability incl. deficiencies:

secondary literature

Justification for type of information:

data is from NTRL Reports

Data source

Reference

Reference 1

Reference Type:

other: Secondary Literature

Title:

INITIAL SUBMISSION: ACUTE EYE IRRITATION IN RABBITS WITH COVER LETTER DATED 12/19/1997

Author:

NTRL

Year:

1997

Bibliographic source:

OTS0559218, 1997

Reference 2

Reference Type:

review article or handbook

Title:

RTECS Number : AJ2430000

Author:

RTECS Database

Year:

2012

Bibliographic source:

RTECS (Registry of Toxic Effects of Chemical Substances):NTIS** National Technical Information Service. (Springfield, VA 22161) Formerly U.S. Clearinghouse for Scientific & Technical Information. Volume(issue)/page/year: OTS0559218

Materials and methods

Test guideline

Qualifier:

according to guideline

Guideline:

other: O.E.C.D. 405(24th February, 1987) and E.C. (92/69/E.E.C, B5- 31st July, 1992) Guidelines

Principles of method if other than guideline:

The potential of the test chemical to induce ocular irritation was evalualed in rabbits according to O.E.C.D. 405(24th February, 1987) and E.C. (92/69/E.E.C, B5- 31st July, 1992) Guidelines

GLP compliance:

not specified

Test material

Test material information

Constituent 1

Reference substance name:

Phenylacetic acid

EC Number:

203-148-6

EC Name:

Phenylacetic acid

Cas Number:

103-82-2

Molecular formula:

C8H8O2

IUPAC Name:

phenylacetic acid

Test material form:

solid

Details on test material:

- Name of test material: Benzeneacetic acid
- Molecular formula: C8H8O2
- Molecular weight: 136.149 g/mole
- Smiles : c1(ccccc1)CC(O)=O
- Inchl: 1S/C8H8O2/c9-8(10)6-7-4-2-1-3-5-7/h1-5H,6H2,(H,9,10)
- Substance type: Organic
- Physical state: solid

Test animals / tissue source

Species:

rabbit

Strain:

New Zealand White

Details on test animals or tissues and environmental conditions:

TEST ANIMALS
- Sex:Male
- Source: Elevage Cunicole de Val de Selle. 80160 Prouzel. France
- Age at study initiation: no data
- Weight at study initiation: 2.7 ± 0.2 kg
- Housing: The animals were housed individually in polystyrene cages
- Diet (e.g. ad libitum): 112 C pelleted diet
- Water (e.g. ad libitum): Drinking water filtered by a EG. Millipore membrane (0.22 micron) was provided ad libitwn.
- Acclimation period: at least five days before the beginning of the study.

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 18 ± 3°C
- Humidity (%): 30 to 70%
- Air changes (per hr): 12 cycles/hour of filtered. non-recycled air.
- Photoperiod (hrs dark / hrs light): 12 h112 h

IN-LIFE DATES: From: To:

Test system

Vehicle:

unchanged (no vehicle)

Controls:

yes, concurrent no treatment

Amount / concentration applied:

TEST MATERIAL
- Amount(s) applied (volume or weight with unit): 100 mg

Duration of treatment / exposure:

The test substance was used in its original form. A single dose of 100 mg of the test substance was introduced into the conjunctival sac of the left eye after gently pulling the lower lid away from the eyeball. The lower and upper eyelids were held together for about one second to avoid any loss of test substance.

Observation period (in vivo):

Ocular reactions were observed approximately one hour, 24, 48 and 72 hours after the administration and then daily until the end of the study (day 22).

Number of animals or in vitro replicates:

3 animals

Details on study design:

REMOVAL OF TEST SUBSTANCE
- Washing (if done): NO, The eyes were not rinsed after administration of the test substance.
- Time after start of exposure: NO

SCORING SYSTEM: Draize scale
Interpretation of the results:
Criteria for irritation
A substance or a preparation is considered irritant for the eyes if. when applied to the eye of the animal. significant severe ocular lesions are caused within 72 hours after exposure and which
persist for 24 hours or more after treatment with the test substance. All the scores at each reading time (24. 48 and 72 hours) and for an effect are used by calculating the respective mean values.

TOOL USED TO ASSESS SCORE: hand-slit lamp / biomicroscope / fluorescein

Results and discussion

In vivo

Results

Results 1

Irritation parameter:

cornea opacity score

Basis:

animal #1

Time point:

24 h

Score:

2

Reversibility:

not specified

Remarks on result:

positive indication of irritation

Results 2

Irritation parameter:

cornea opacity score

Basis:

animal #2

Time point:

48 h

Score:

4

Reversibility:

not specified

Remarks on result:

positive indication of irritation

Results 3

Irritation parameter:

cornea opacity score

Basis:

animal #3

Time point:

72 h

Score:

2.3

Reversibility:

not specified

Remarks on result:

positive indication of irritation

Results 4

Irritation parameter:

iris score

Basis:

mean

Time point:

24/48 h

Score:

1

Reversibility:

not specified

Remarks on result:

positive indication of irritation

Results 5

Irritation parameter:

chemosis score

Basis:

animal #1

Time point:

24 h

Score:

3.3

Reversibility:

not specified

Remarks on result:

positive indication of irritation

Results 6

Irritation parameter:

chemosis score

Basis:

animal #2

Time point:

other: 48,72 hours

Score:

3

Reversibility:

not specified

Remarks on result:

positive indication of irritation

Results 7

Irritation parameter:

conjunctivae score

Remarks:

redness

Basis:

animal #1

Time point:

24 h

Score:

3

Reversibility:

not specified

Remarks on result:

positive indication of irritation

Results 8

Irritation parameter:

conjunctivae score

Remarks:

redness

Basis:

animal #2

Time point:

48 h

Score:

2.7

Reversibility:

not specified

Remarks on result:

positive indication of irritation

Results 9

Irritation parameter:

conjunctivae score

Remarks:

redness

Basis:

mean

Time point:

72 h

Score:

3

Reversibility:

not specified

Remarks on result:

positive indication of irritation

Irritant / corrosive response data:

Slight to severe conjunctival reactions were observed in all animals: very slight to severe chemosis (grades 1 to 4). very slight to moderate redness of the conjunctivae (grade 1 to 3) and clear or whitish purulent discharge were noted. from day 1 up to day 17 at the latest.
A slight iritis (grade 1) was observed in two animals on day 2; it persisted up to day 12 or 14. Reading was masked by corneal opacity in the remaining animal.
A moderate or severe corneal opacity (grade 3 or 4) was noted in all animals on day 1: a slight to severe corneal opacity (grades 2 to 4) persisted up to the end of the observation period (day 22) in two animals. The remaining animal was killed on day 7 for ethical reasons, because of the severity of ocular reactions.
A whitening of the conjunctivae was noted in all animals on day 1; it persisted up to day 17 at the latest. Neovascularisation was noted in two animals from day 5 up to day 14 or from day 7 up to the end of the observation period (day 22) and alopecia around the eye was recorded in one animal, from day 11 up to day 20.

Any other information on results incl. tables

Individual ocular examinations and mean values of the scores recorded at each readings (24, 48 and 72 hours) for each animal

Rabbit number	Region of the eyes	Description of the ocular reactions	Scores				Mean irritation score	Interpretation (+)(-)
			1h D1	24h	48h	72h
1	Conjunctivae	chemosis	3	4	3	3	3.3	+
		Redness	2	3	3	3	3	+
		Discharge	2	S	S	S	(2)
	Iris		0	1	1	1	1	+
	Corneal opacity	intensity	3	2	2	2	2	+
		Area	2	4	4	3	3.7
	other		B	B	B	B
	Fluorescein		/	U	U	U
2	Conjunctivae	chemosis	3	3	3	3	3.0	+
		Redness	1	2	3	3	2.7	+
		Discharge	0	S	S	S	(2)
	Iris		OP	OP	OP	OP	(2)	(2)
	Corneal opacity	intensity	4	4	4	4	4	+
		Area	1	2	2	3	2.3
	other		B	B	B	B
	Fluorescein		/	U	U	U
3	Conjunctivae	chemosis	2	3	3	3	3	+
		Redness	2	3	3	3	3	+
		Discharge	0	S	S	S	(2)
	Iris		0	1	1	1	1	+
	Corneal opacity	intensity	4	3	2	2	2.3	+
		Area	2	2	2	2	(2)
	other		B	B	B	B
	Fluorescein		/	U	U	U

(1) = mean of scores on days 2, 3 and 4

h = hour

D = day

(+) = irritant according to EEC criteria

(-) = Non-irritant according to EEC criteria

(2) = not calculated.

U = Fluorescein batches Nos. 5691 and 7239

I = Fluorescein not used

S = Whitish purulent discharge

Applicant's summary and conclusion

Interpretation of results:

Category 2 (irritating to eyes) based on GHS criteria

Conclusions:

Slight to severe conjunctival reactions were observed in all animals: very slight to severe chemosis (grades 1 to 4). very slight to moderate redness of the conjunctivae (grade 1 to 3) and clear or whitish purulent discharge were noted. from day 1 up to day 17 at the latest.
A slight iritis (grade 1) was observed in two animals on day 2; it persisted up to day 12 or 14. Reading was masked by corneal opacity in the remaining animal.
A moderate or severe corneal opacity (grade 3 or 4) was noted in all animals on day 1: a slight to severe corneal opacity (grades 2 to 4) persisted up to the end of the observation period (day 22) in two animals. The remaining animal was killed on day 7 for ethical reasons, because of the severity of ocular reactions.
Based on these observations, the test chemical was considered to be severely irritating to rabbit eyes.
A whitening of the conjunctivae was noted in all animals on day 1; it persisted up to day 17 at the latest. Neovascularisation was noted in two animals from day 5 up to day 14 or from day 7 up to the end of the observation period (day 22) and alopecia around the eye was recorded in one animal, from day 11 up to day 20.

Executive summary:

The potential of the test chemical to induce ocular irritation was evaluated in rabbits according to O.E.C.D. 405(24th February, 1987) and E.C. (92/69/E.E.C, B5- 31st July, 1992) Guidelines. 3 Male New Zealand White rabbits were used for the study. The test substance was used in its original form. A single dose of 100 mg of the test substance was introduced into the conjunctival sac of the left eye after gently pulling the lower lid away from the eyeball. The lower and upper eyelids were held together for about one second to avoid any loss of test substance. The right eye which remained untreated, served as a control. The eyes were not rinsed after administration of the test substance.

The eyes were examined approximately one hour, 24, 48 and 72 hours after administration of the test substance following the O.E.C.D. and E.C. guidelines:

· when there is no evidence of irritation after 1 hours. The study is ended.

· when there is persistent ocular irritation after 72 hours, the observation period is extended to a maximum of 21 days (until day 22) in order to determine the progress of the lesions and their reversibility.

· when severe irritant effects are observed, the animals are killed on humane ground.

Any change in the animals' behaviour was noted. Ocular reactions were observed approximately one hour, 24, 48 and 72 hours after the administration and then daily until the end of the study (day 22).

Slight to severe conjunctival reactions were observed in all animals: very slight to severe chemosis (grades 1 to 4). Very slight to moderate redness of the conjunctivae (grade 1 to 3) and clear or whitish purulent discharge were noted from day 1 up to day 17 at the latest.

A slight iritis (grade 1) was observed in two animals on day 2; it persisted up to day 12 or 14. Reading was masked by corneal opacity in the remaining animal.

A moderate or severe corneal opacity (grade 3 or 4) was noted in all animals on day 1: a slight to severe corneal opacity (grades 2 to 4) persisted up to the end of the observation period (day 22) in two animals. The remaining animal was killed on day 7 for ethical reasons, because of the severity of ocular reactions.

A whitening of the conjunctivae was noted in all animals on day 1; it persisted up to day 17 at the latest. Neovascularisation was noted in two animals from day 5 up to day 14 or from day 7 up to the end of the observation period (day 22) and alopecia around the eye was recorded in one animal, from day 11 up to day 20.

Based on these observations, the test chemical was considered to be severely irritating to rabbit eyes.