Methyl (R)-2-(4-hydroxyphenoxy)propionate

Eye irritation

Administrative data

Endpoint:

eye irritation: in vivo

Type of information:

experimental study

Adequacy of study:

key study

Study period:

Not reported; test material application took place on the 08 July 1993 in the first animal and on the 22 July 1993 in the following two animals

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

guideline study

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

1992

Report date:

1992

Materials and methods

Test guideline

Test guideline 1

Qualifier:

according to guideline

Guideline:

OECD Guideline 405 (Acute Eye Irritation / Corrosion)

Version / remarks:

1987

Deviations:

no

Test guideline 2

Qualifier:

according to guideline

Guideline:

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

Version / remarks:

1984

Deviations:

no

GLP compliance:

yes

Test material

Test material information

Constituent 1

Reference substance name:

Methyl (R)-2-(4-hydroxyphenoxy)propionate

EC Number:

411-950-4

EC Name:

Methyl (R)-2-(4-hydroxyphenoxy)propionate

Cas Number:

96562-58-2

Molecular formula:

C10H12O4

IUPAC Name:

methyl (2R)-2-(4-hydroxyphenoxy)propanoate

Test material form:

solid

Details on test material:

- Appearance: Brown solid
- Storage conditions of test material: Refrigerator

Test animals / tissue source

Species:

rabbit

Strain:

Vienna White

Details on test animals or tissues and environmental conditions:

TEST ANIMALS
- Weight at study initiation: Males: 3.34 kg
- Housing: Animals were housed individually in cages made of stainless steel with wire mesh walk floors (floor area 40 x 51 cm). There was no bedding in the cages but sawdust in the waste trays
- Diet: About 130 g per animal per day
- Water: About 250 mL tap water per animal per day
- Acclimation period: At least 8 days

ENVIRONMENTAL CONDITIONS
- Temperature: 20 to 24 °C
- Humidity: 30 to 70 % (relative)
- Air changes: Not specified; the animals were housed ln fully air-conditioned rooms
- Photoperiod: 12 hours of light / 12 hours of darkness (lights on 06:00 to 18:00)

Test system

Vehicle:

unchanged (no vehicle)

Controls:

yes, concurrent no treatment

Amount / concentration applied:

TEST MATERIAL
- Amount(s) applied (volume or weight with unit): 0.1 mL. The solid test material was warmed to 70 °C until liquid. The undiluted material cooled to body temperature was applied.

Duration of treatment / exposure:

The animals were treated with a single application to the conjunctival sac of the right eyelid.

Observation period (in vivo):

Animal number 1 was observed for 15 days after test material application (first test). The remaining two animals were observed for 21 days (second test)

Number of animals or in vitro replicates:

Three male animals

Details on study design:

REMOVAL OF TEST SUBSTANCE
- Washing (if done): The test material was not washed out

SCORING SYSTEM:
- Chemosis and Corneal Opacity (and degree of density)
0 = None
1 = Slight
2 = Well Defined
3 = Severe
4 = Very Severe

- Conjunctival Redness
0 = Normal
1 = Slight
2 = Well Defined
3 = Severe

- Discharge
0 = Normal
1 = Slightly Increased
2 = Clearly Increased
3 = Distinctly Increased

- Iris
0 = Normal
1 = Circumcorneal injection
2 = Iritis

Results and discussion

In vivo

Results

Results 1

Irritation parameter:

cornea opacity score

Basis:

mean

Time point:

24/48/72 h

Score:

1.33

Max. score:

4

Reversibility:

not fully reversible within: 21 days

Remarks on result:

positive indication of irritation

Results 2

Irritation parameter:

iris score

Basis:

mean

Time point:

24/48/72 h

Score:

1

Max. score:

2

Reversibility:

fully reversible within: 15 days

Remarks on result:

positive indication of irritation

Results 3

Irritation parameter:

conjunctivae score

Remarks:

redness

Basis:

mean

Time point:

24/48/72 h

Score:

2

Max. score:

3

Reversibility:

not fully reversible within: 21 days

Remarks on result:

positive indication of irritation

Results 4

Irritation parameter:

chemosis score

Basis:

mean

Time point:

24/48/72 h

Score:

2 011

Max. score:

4

Reversibility:

not fully reversible within: 21 days

Remarks on result:

positive indication of irritation

Results 5

Irritation parameter:

other: discharge

Basis:

mean

Time point:

24/48/72 h

Score:

1.89

Max. score:

3

Reversibility:

not fully reversible within: 21 days

Remarks on result:

positive indication of irritation

Irritant / corrosive response data:

Effects were seen on all three eyes for all parameters investigated. In the first treated animal, all signs had reversed after 15 days. Animals 2 and 3 both still showed effects after 21 days, with the corneal scores for animal number 3 being at the highest possible value at the 15 and 21 days observation points.

Any other information on results incl. tables

Table 1. Results of Acute Eye irritation

Reading	Animal	Cornea		Iris	Conjunctivae			Symptoms
		Opacity	Area		Redness	Chemosis	Discharge
1 hour	1	2	2	0	2	2	2	LC
	2	1	4	0	2	3	2
	3	1	4	0	2	2	2	LC
24 hours	1	2	1	1	2	3	2	LC/ PC/DB/S
	2	1	4	1	2	2	2	PC/DB
	3	1	4	1	2	3	2	PC/DB/S
48 hours	1	2	1	1	2	2	2	LC/PC/S
	2	1	4	1	2	2	2	PC/S
	3	1	4	1	2	2	2	PC/S
72 hours	1	2	1	1	2	1	1	LC/PC
	2	1	4	1	2	2	2	PC/S
	3	1	4	1	2	2	2	PC/S
8 days	1	1	2	0	1	0	0	MV
	2	2	2	0	1	1	0	LC/MV
	3	2	3	1	2	1	1	LC/PC/MV
15 days	1	0	0	0	0	0	0	MV†
	2	2	2	0	1	0	0	LC/MV
	3	4	1	0*	2	1	1	LC/MV/S/RE‡
21 days	2	1	2	0	1	0	0	LC/MV
	3	4	1	0	2	1	1	LC/MV/RE

*Findings which could not be read (for reason see symptoms): If in one or two animals assessments referring to the same characteristic cannot be made at a particular reading, the mean rounded to the nearest whole number of the values that can be read is inserted instead.

 

Explanation of symptoms:

‡Irritation index could not be read because of marginal vascularisation of the cornea

†Test discontinued after 15 days

DB = Discharge of blood

LC = Loss of corneal tissue

MV = Marginal vascularisation of the cornea

PC = Pupil Contracted

RE = Small retractions in the eyelids

S = Suppuration

Applicant's summary and conclusion

Interpretation of results:

other: Classified as Category 1 in accordance with EU criteria

Conclusions:

Under the conditions of the study, the test material was found to be irritating to the eye of the rabbit, with the effects not being fully reversible within 21 days.

Executive summary:

A study was conducted to investigate the potential of the test material to cause eye irritation in accordance with the standardised guidelines OECD 405 and EU Method B.5 under GLP conditions.

The right eye of each of three Vienna White rabbits was treated with a single 0.1 mL dose of test material in the conjunctival sac. The left eye of the rabbits was left untreated and served as a negative control. One rabbit was dosed initially and observed for a period of 15 days. Two further rabbits were then dosed and observed for a period of 21 days. The treated eyes were assed for corneal opacity, redness of the conjunctivae, chemosis, effects on the iris and discharge after 1, 24, 48 and 72 hours, then after 8 and 15 days. A final observation took place after 21 days for the second and third animals treated.

Effects were seen on all three eyes for all parameters investigated. In the first treated animal, all signs had reversed after 15 days. Animals 2 and 3 both still showed effects after 21 days, with the corneal scores for animal number 3 being at the highest possible value at the 15 and 21 days observation points.

Under the conditions of the study, the test material was found to be irritating to the eye of the rabbit, with the effects not being fully reversible within 21 days.