Methyl (R)-amino(4-hydroxyphenyl)acetate

Eye irritation

Administrative data

Endpoint:

eye irritation: in vivo

Type of information:

experimental study

Adequacy of study:

key study

Study period:

end on 9-APR-1996

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

other: study performed according to OECD guideline and GLP

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

1996

Report date:

1996

Materials and methods

Test guideline

Qualifier:

according to guideline

Guideline:

OECD Guideline 405 (Acute Eye Irritation / Corrosion)

Deviations:

no

GLP compliance:

yes

Test material

Test material information

Constituent 1

Reference substance name:

Methyl (R)-amino(4-hydroxyphenyl)acetate

EC Number:

253-657-2

EC Name:

Methyl (R)-amino(4-hydroxyphenyl)acetate

Cas Number:

37763-23-8

Molecular formula:

C9H11NO3

IUPAC Name:

methyl (2R)-2-amino-2-(4-hydroxyphenyl)acetate

Details on test material:

- Name of test material (as cited in study report): FGHM
- Molecular formula (if other than submission substance): C9H11NO3
- Structural formula attached as image file (if other than submission substance): see Fig.
- Substance type: monoconstituent substance
- Physical state: powder
- Stability under test conditions: not indicated
- Storage condition of test material: in refrigerator in the dark

Test animals / tissue source

Species:

rabbit

Strain:

New Zealand White

Details on test animals or tissues and environmental conditions:

TEST ANIMALS
- Source: Broekman Institute, Someren, The Netherlands
- Age at study initiation: approx. 7 or 10 weeks
- Weight at study initiation: 1378 to 2086 g
- Housing: individually in labelled cages with perforated floor
- Diet: standard laboratory rabbit diet, approx. 100 g per day. In addition, hay was provided once a week.
- Water: free access to tap water diluted with decalcified water.
- Acclimation period: at least 5 days before start of the treatment under laboratory conditions.

ENVIRONMENTAL CONDITIONS
- Temperature: 21 °C
- Humidity: 50%
- Air changes: approx. 15 air changes per hour
- Photoperiod: 12 hrs dark / 12 hrs light

IN-LIFE DATES: data not available

Test system

Vehicle:

unchanged (no vehicle)

Controls:

other: The other eye remained untreated and served as the reference control.

Amount / concentration applied:

TEST MATERIAL
- Amount applied: 26 +/- 0.9 mg (approx. 0.1 mL)
- Concentration: undiluted

Observation period (in vivo):

72 hours

Number of animals or in vitro replicates:

3 males

Details on study design:

REMOVAL OF TEST SUBSTANCE
- Washing (if done): no

SCORING SYSTEM: according to OECD guideline

Results and discussion

In vivo

Results

Results 1

Irritation parameter:

cornea opacity score

Basis:

mean

Time point:

other: mean value (24, 48, 72h)

Score:

0

Max. score:

4

Results 2

Irritation parameter:

iris score

Basis:

mean

Time point:

other: mean value (24, 48, 72h)

Score:

0

Max. score:

2

Reversibility:

fully reversible within: 24 hours

Results 3

Irritation parameter:

conjunctivae score

Basis:

mean

Time point:

other: mean value (24, 48, 72h)

Score:

0.3

Max. score:

3

Reversibility:

fully reversible within: 48 hours

Results 4

Irritation parameter:

chemosis score

Basis:

mean

Time point:

other: mean value (24, 48, 72h)

Score:

0

Max. score:

4

Reversibility:

fully reversible within: 24 hours

Irritant / corrosive response data:

Iridic irritation (grade 1) was noted in 2 animals at one hour after instillation only.
The irritation of the conjuntivae consisted of redness, chemosis and discharge (all at grade 1), which has resolved after 48h of treatment.
No corneal opacity was onserved and treatment of the eyes with 2% fluorescein, 24h after test substance instillation revealed no corneal epithelial damage in any of the animals.
There was no evidence of ocular corrosion.

Other effects:

No staining of the peri-ocular tissues by the test substance was noted.
Remnants of the test substance were present in the eye of all animals 1h after instillation.
No symptoms of systemic toxicity were observed in the animals during the test period and no mortality occurred.

Any other information on results incl. tables

Table1: Irritant/corrosive response data for each animal at each observation time up to removal of each animal from the test

Score at time point / Reversibility	Cornea	Iris	Conjunctivae	Chemosis
	Max. score: 4	Max. score: 2	Max. score: 3	Max. score: 4
60 min	0 / 0 / 0	0 / 1 / 1	1 / 1 / 1	0 / 0 / 1
24 h	0 / 0 / 0	0 / 0 / 0	1 / 1 / 1	0 / 0 / 0
48 h	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
Average 24h, 48h, 72h	0 / 0 / 0	0 / 0 / 0	0.3 / 0.3 / 0.3	0 / 0 / 0
Reversibility	-	yes	yes	yes
Average time for reversion	-	After 24h	After 48h	After 24h

Applicant's summary and conclusion

Interpretation of results:

not irritating

Remarks:

Migrated information Criteria used for interpretation of results: EU

Conclusions:

HPGM (FGHM) is not irritating to the eye in the rabbit.

Executive summary:

In a primary eye irritation study (OECD 405, GLP), 26 mg (ca. 0.1 mL) of undiluted HPGM (FGHM) was instilled into the conjunctival sac of one eye of New Zealand White rabbits (3 males). Animals then were observed for 72 hours. Irritation was scored by the method of OECD guideline.

 

Iridic irritation (grade 1) was noted in 2 animals at one hour after instillation only.

The irritation of the conjuntivae consisted of redness, chemosis and discharge (all at grade 1), which has resolved after 48h of treatment.

No corneal opacity was onserved and treatment of the eyes with 2% fluorescein, 24h after test substance instillation revealed no corneal epithelial damage in any of the animals.

There was no evidence of ocular corrosion.

The mean scores at 24, 48 and 72h were:

-        Cornea, Iris, Chemosis : 0

-        Conjunctivae : 0.3

 

According to EC criteria for classification of dangerous substances (DSD directive and CLP regulation), HPGM (FGHM) is not classified as irritating to the eyes.