(R)-α-phenylethylammonium (-)-(1R, 2S)-(1,2-epoxypropyl)phosphonate monohydrate

Eye irritation

Administrative data

Endpoint:

eye irritation: in vivo

Type of information:

experimental study

Adequacy of study:

key study

Study period:

July 21, 1994 - July 25, 1994

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

guideline study

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

1994

Report date:

1994

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:

(R)-α-phenylethylammonium (-)-(1R, 2S)-(1,2-epoxypropyl)phosphonate monohydrate

EC Number:

418-570-8

EC Name:

(R)-α-phenylethylammonium (-)-(1R, 2S)-(1,2-epoxypropyl)phosphonate monohydrate

Cas Number:

25383-07-7

Molecular formula:

C11H20NO5P

IUPAC Name:

(R)-α-phenylethylammonium (-)-(1R, 2S)-(1,2-epoxypropyl)phosphonate monohydrate

Details on test material:

- Name of test material (as cited in study report): Fosfomycin PEA salt
- Physical state: white crystalline powder
- Lot/batch No.: 4177
- Expiration date of the lot/batch: at least 3 years from the manufacturing date
- Stability under test conditions: at least 3 years
- Storage condition of test material: plastic bag in a cartboard box, at room temperature protected from the light
- Other: manufacturing date: june 10, 1994

Test animals / tissue source

Species:

rabbit

Strain:

New Zealand White

Details on test animals or tissues and environmental conditions:

TEST ANIMALS
- Source: Conelli s.n.c
- Age at study initiation: 2-3 months
- Weight at study initiation: 2.0-3.0 kg
- Housing: individual caging in T06C air conditioned rooms. Each rabbit was caged in metal caged measuring 62x47.5x38h cm with stainless feeder.
- Diet (e.g. ad libitum): Ad libitum (GLP 2RB15 certificate pelleted diet)
- Water (e.g. ad libitum): Ad libitum (from the municipal water main system, filtered)
- Acclimation period: about 4 months

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 20 ± 2 ºC
- Humidity (%):50 ± 15 %
- Air changes (per hr): 15 per hour
- Photoperiod (hrs dark / hrs light): 12 h dark/12 h light (7 a.m. - 7 p.m.)

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 g/animal

Duration of treatment / exposure:

24 h

Observation period (in vivo):

at 1, 24, 48 and 72 h after the test article application.

Number of animals or in vitro replicates:

3

Details on study design:

REMOVAL OF TEST SUBSTANCE
- Washing (if done): Yes, the eyes of the test animals were washed out
- Time after start of exposure: 24 h

SCORING SYSTEM:
CORNEA:
Opacity: degree of density (most dense are taken for reading):
No ulceration or opacity: 0
Scattered or diffuse areas of opacity (other than slight dulling of normal luster), details of iris clearly visible: 1
Easily discernible translucent area, details of iris slightly obscured: 2
Nacrous area, no details of iris visible, size of pupil barely discernible: 3
Opaque cornea, iris not discernible through the opacity: 4
IRIS:
Normal: 0
Markedly deepened rugae, congestion, swelling, moderate circumcorneal hyperemia, or injection, any of these or combinations of any thereof, iris still reacting to light (sluggish reaction is positive): 1
No reaction to light, hemorrhage, gross destruction (any or all of these): 2
CONJUNCTIVAE:
Redness (refers to palpebral and bulbar conjunctivae, cornea and iris):
Blood vessels normal: 0
Some blood vessels definitely hyperemic (injected): 1
Diffuse, crimson colour, individual vessels not easily discernible: 2
Diffuse beefy red: 3
Chemosis: lids and/or nictating membranes:
No swelling: 0
Any swelling above normal (includes nictating membranes): 1
Obvious swelling with partial eversion of lids: 2
Swelling with lids about half closed: 3
Swelling with lids more than half closed: 4

TOOL USED TO ASSESS SCORE: hand-slit lamp / biomicroscope / fluorescein: After the 24-hour reading, corneal epithelium defects were examined after instillation of one drop of 1% sodium fluorescein and successive washing out with sterile saline.

Results and discussion

In vivo

Results

Results 1

Irritation parameter:

cornea opacity score

Basis:

animal #1

Time point:

other: 24-72 h

Score:

0

Max. score:

0

Results 2

Irritation parameter:

iris score

Basis:

animal #1

Time point:

other: 24-72 h

Score:

0

Max. score:

0

Results 3

Irritation parameter:

conjunctivae score

Remarks:

redness

Basis:

animal #1

Time point:

other: 24-72 h

Score:

0.33

Max. score:

1

Reversibility:

fully reversible

Results 4

Irritation parameter:

chemosis score

Basis:

animal #1

Time point:

other: 24-72 h

Score:

0

Max. score:

0

Results 5

Irritation parameter:

cornea opacity score

Basis:

animal #2

Time point:

other: 24-72 h

Score:

0

Max. score:

0

Results 6

Irritation parameter:

iris score

Basis:

animal #2

Time point:

other: 24-72 h

Score:

0

Max. score:

0

Results 7

Irritation parameter:

conjunctivae score

Remarks:

redness

Basis:

animal #2

Time point:

other: 24-72 h

Score:

0

Max. score:

0

Results 8

Irritation parameter:

chemosis score

Basis:

animal #2

Time point:

other: 24-72 h

Score:

0

Max. score:

0

Results 9

Irritation parameter:

cornea opacity score

Basis:

animal #3

Time point:

other: 24-72 h

Score:

0

Max. score:

0

Results 10

Irritation parameter:

iris score

Basis:

animal #3

Time point:

other: 24-72 h

Score:

0

Max. score:

0

Results 11

Irritation parameter:

conjunctivae score

Remarks:

redness

Basis:

animal #3

Time point:

other: 24-72 h

Score:

0

Max. score:

0

Results 12

Irritation parameter:

chemosis score

Basis:

animal #3

Time point:

other: 24-72 h

Score:

0

Max. score:

0

Any other information on results incl. tables

Mortality: No animals died during the observation period.

Observation of clinical signs and behaviour: No clinical signs or behavioural alterations were noted in any treated rabbit.

Eye evaluation:

Slight lacrimation was noted only one hour after the test article application in all rabbits.

Eye reaction (individual)	Observation made at:	No. of animals
		135M	136M	137M
CORNEA	60 mins.	0	0	0
	24 hrs	0	0	0
	48 hrs	0	0	0
	72 hrs	0	0	0
IRIS	60 mins.	0	0	0
	24 hrs	0	0	0
	48 hrs	0	0	0
	72 hrs	0	0	0
CONJUNCTIVAE Redness	60 mins.	1	1	1
	24 hrs	1	0	0
	48 hrs	0	0	0
	72 hrs	0	0	0
CONJUNCTIVAE Chemosis	60 mins.	1	0	1
	24 hrs	0	0	0
	48 hrs	0	0	0
	72 hrs	0	0	0

Applicant's summary and conclusion

Interpretation of results:

GHS criteria not met

Remarks:

EU criteria.

Conclusions:

The acute eye irritation study in New Zealand White rabbits treated with a single administration of test article Fosfomycin PEA salt (0.1 g/animal) has to be considered "non irritant" for the eye.

Executive summary:

The acute eye irritation study in New Zealand White rabbits treated with a single administration of test article Fosfomycin PEA salt followed the OECD Guideline 405. 3 rabbits were used in the study. The test article (0.1 g) was placed in the conjunctival sac of the right eye of each animal for 24 hours. The other eye (left), remaining untreated, served as control. Clinical observations of cornea, iris, conjunctivae and chemosis were made at 1, 24, 48 and 72 hours after the test article application. After the 24 -hours reading, corneal epithelium defects were examined.

No animals died during the study.

No general clinical signs were seen in any animal.

At the application site, slight reversible irritative ocular changes were observed in all treated rabbits. No signs were evident 48 hours after the test article application in any animal.

In conclusion, the test article Fosfomycin PEA salt, when administered by ocular route to rabbits under the experimental conditions adopted, has to be considered "NON IRRITANT" for the eye.