Potassium (R)-[(3-ethoxy-1-methyl-3-oxoprop-1-enyl)amino]phenylacetate

Eye irritation

Administrative data

Endpoint:

eye irritation: in vivo

Type of information:

experimental study

Adequacy of study:

key study

Study period:

end on 8 July 1993

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

other: screening test, sufficiently described

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

1993

Report date:

1993

Materials and methods

Test guideline

Qualifier:

equivalent or similar to guideline

Guideline:

OECD Guideline 405 (Acute Eye Irritation / Corrosion)

Deviations:

yes

Remarks:

screening test, only one animal used

GLP compliance:

no

Test material

Test material information

Constituent 1

Reference substance name:

Potassium (R)-[(3-ethoxy-1-methyl-3-oxoprop-1-enyl)amino]phenylacetate

EC Number:

213-510-5

EC Name:

Potassium (R)-[(3-ethoxy-1-methyl-3-oxoprop-1-enyl)amino]phenylacetate

Cas Number:

961-69-3

Molecular formula:

C14H17NO4.K

IUPAC Name:

potassium [(3-ethoxy-1-methyl-3-oxoprop-1-en-1-yl)amino](phenyl)acetate

Details on test material:

- Name of test material (as cited in study report): FG-KZE
- Substance type: monoconstituent substance
- Physical state: data not available
- Analytical purity: data not available
- Impurities (identity and concentrations): data not available
- Purity test date: data not available
- Lot/batch No.: 989 A
- Expiration date of the lot/batch: data not available
- Stability under test conditions: data not available
- Storage condition of test material: data not available

Test animals / tissue source

Species:

rabbit

Strain:

New Zealand White

Details on test animals or tissues and environmental conditions:

TEST ANIMALS
- Source, Age at study initiation, Weight at study initiation, Fasting period before study, Housing, Diet, Water, Acclimation period: data not available

ENVIRONMENTAL CONDITIONS
- Temperature, Humidity, Air changes, Photoperiod: data not available

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: 50 mg (specific gravity: 0.5)
- Concentration: undiluted

Observation period (in vivo):

21 days

Number of animals or in vitro replicates:

one animal

Details on study design:

REMOVAL OF TEST SUBSTANCE
- Washing: no

SCORING SYSTEM: Draize scale, according to OECD guideline

TOOL USED TO ASSESS SCORE: data not available

Results and discussion

In vivo

Results

Results 1

Irritation parameter:

cornea opacity score

Basis:

animal #1

Time point:

other: mean value (24, 48, 72h

Score:

1

Max. score:

4

Reversibility:

fully reversible within: 14 days

Results 2

Irritation parameter:

iris score

Basis:

animal #1

Time point:

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

Score:

1

Max. score:

2

Reversibility:

fully reversible within: 7 days

Results 3

Irritation parameter:

conjunctivae score

Basis:

animal #1

Time point:

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

Score:

3

Max. score:

3

Reversibility:

fully reversible within: 21 days

Results 4

Irritation parameter:

chemosis score

Basis:

animal #1

Time point:

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

Score:

1.7

Max. score:

4

Reversibility:

fully reversible within: 7 days

Irritant / corrosive response data:

Instillation of FG-KZE (batch 989 A) in a rabbit eye resulted in adverse effects on the cornea, iris and the conjunctivae. The iridic irritation had resolved within 7 days, the corneal injury had resolved w ithin 14 days and the irritation of the conjunctivae had resolved within 21 days after instillation.

Other effects:

At 1 h: The size of the pupil of the treated eye was reduced in comparison with the pupil of the reference eye. Grey/white discolouration of the nictitating membrane, as a sign of necrosis.
At 1, 24, 48 and 72h: Grey/white discolouration of the nictitating membrane and eyelids, as a sign of necrosis. Lacrimation was observed.
At 7 days: Neovascularisation of the cornea. Grey/white discolouration of the nictitating membrane and eyelids, as a sign of necrosis.

Any other information on results incl. tables

Table 1: Irritant/corrosive response

Score at time point / Reversibility	Cornea	Iris	Conjunctivae	Chemosis
	Max. score: 4	Max. score: 2	Max. score: 3	Max. score: 4
60 min	1	1	3	2
24 h	1	1	3	2
48 h	1	1	3	2
72 h	1	1	3	1
7 days	1	0	3	0
14 days	0	0	1	0
21 days	0	0	0	0
Average 24h, 48h, 72h	1	1	3	1.7
Reversibility*)	yes	yes	yes	yes
Average time (unit) for reversion	After  14 days	After 7 days	After 21 days	After 7 days

Applicant's summary and conclusion

Interpretation of results:

irritating

Remarks:

Migrated information Criteria used for interpretation of results: EU

Conclusions:

PG-ds (potassium (R)-[(3-ethoxy-1-methyl-3-oxoprop-1-enyl)amino]phenylacetate) is an eye irritant.

Executive summary:

In a primary eye irritation study, 50 mg of undiluted PG-ds (potassium (R)-[(3-ethoxy-1-methyl-3-oxoprop-1-enyl)amino]phenylacetate) was instilled into the conjunctival sac of one eye of an albino rabbit (New Zealand White) after gently pulling the lower lid away from the eyeball. The lids were gently held together for about one second to prevent loss of the test substance. The other eye remained untreated and served as the reference control. Irritation was scored by the method of Draize.

 

Instillation of PG-ds (potassium (R)-[(3-ethoxy-1-methyl-3-oxoprop-1-enyl)amino]phenylacetate) in a rabbit eye resulted in adverse effects on the cornea, iris and the conjunctivae. The iridic irritation had resolved within 7 days, the corneal injury had resolved w ithin 14 days and the irritation of the conjunctivae had resolved within 21 days after instillation.

According to the EEC criteria for classification and labelling requirements, the mean value of the scores for each type of lesion is the following (mean of 24, 48 and 72h):

-       Corneal opacity: 1

-       Iris: 1

-       Conjunctivae (redness): 3

-       Conjunctivae (chemosis): 1.7

 

In this study, PG-ds (potassium (R)-[(3-ethoxy-1-methyl-3-oxoprop-1-enyl)amino]phenylacetate) is an eye irritant based on EU criteria (according to DSD and CLP).