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

Endpoint summary

Description of key information

Skin irritation: Key study: Test method according to EU Method B.4 and OECD Guideline 404. GLP study. The test substance was considered "non-irritant" for the skin.

Eye irritation: Key study: Test method according to OECD Guideline 404. GLP study. The test substance was considered "non-irritant" for the eye.

Key value for chemical safety assessment

Skin irritation / corrosion

Link to relevant study records

Reference

Endpoint:

skin irritation: in vivo

Type of information:

experimental study

Adequacy of study:

key study

Study period:

July 12, 1994 - July 15, 1994

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

guideline study

Qualifier:

according to guideline

Guideline:

EU Method B.4 (Acute Toxicity: Dermal Irritation / Corrosion)

Deviations:

no

Qualifier:

according to guideline

Guideline:

OECD Guideline 404 (Acute Dermal Irritation / Corrosion)

GLP compliance:

yes

Species:

rabbit

Strain:

New Zealand White

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Source: Conelli s.n.c
- Age at study initiation: 2-3 months
- Weight at study initiation: 2-3 kg
- Housing: individual caging in T06C air conditioned room. Each rabbit was caged in metal cages 62x47x48h cm with stainless feeder.
- Diet (e.g. ad libitum): ad libitum (GLP 2 RB 15 certificate pelleted diet)
- Water (e.g. ad libitum): ad libitum (from the municipal water main system, filtered).
- Acclimation period: about 3 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 (artificial lighting)

Type of coverage:

occlusive

Preparation of test site:

shaved

Vehicle:

unchanged (no vehicle)

Controls:

yes, concurrent no treatment

Amount / concentration applied:

TEST MATERIAL
- Amount(s) applied (volume or weight with unit): 0.5 g/animal

Duration of treatment / exposure:

3 minutes, 1 and 4 hours

Observation period:

Immediately after 3 minute and the 1 hour-exposure period and at 72 hours in the first rabbit and at 1, 24, 48 and 72 hours after the 4-hour exposure period (all rabbits).

Number of animals:

3

Details on study design:

TEST SITE
- Area of exposure: 6 cm2
- Type of wrap if used: covered with a gauze patch loosely held in contact with the skin by an impermeable, non-irritant, hypoallergenic tape.

SCORING SYSTEM:
Erythema and Eschar formation:
No erythema: 0
Very slight erythema (barely perceptible): 1
Well-defined erythema: 2
Moderate to severe erythema: 3
Severe erythema (beet redness) to slight eschar formation (injuries in depth): 4
Edema formation:
No edema: 0
Very slight edema (barely perceptible): 1
Slight edema (edges of area well defined by definite raising): 2
Moderate edema (raised approximately 1 mm): 3
Severe erythema (raised more than 1 mm and extending beyond area of exposure): 4

Irritation parameter:

erythema score

Basis:

animal #1

Time point:

other: 24-72 h

Score:

0

Max. score:

0

Irritation parameter:

edema score

Basis:

animal #1

Time point:

other: 24-72 h

Score:

0

Max. score:

0

Irritation parameter:

erythema score

Basis:

animal #2

Time point:

other: 24-72 h

Score:

0

Max. score:

0

Irritation parameter:

edema score

Basis:

animal #2

Time point:

other: 24-72 h

Score:

0

Max. score:

0

Irritation parameter:

erythema score

Basis:

animal #3

Time point:

other: 24-72 h

Score:

0

Max. score:

0

Irritation parameter:

edema score

Basis:

animal #3

Time point:

other: 24-72 h

Score:

0

Max. score:

0

Mortality: No animals died

Observation of clinical signs and behaviour: No clinical signs or behavioural alterations were noted.

Skin evaluation: At the application sites no signs of dermal irritancy were evident in any treated rabbit.

Table 1. Dermal reactions (individual).

Animal no. 135M.	Observation at	Exposure period
		3 min	1 h
1)     Erythema and eschar	3 min	0	-
	1 h	0	0
	72 h	0	0
2)     Edema	3 min	0	-
	1 h	0	0
	72 h	0	0

 

Table 2. Dermal reactions (individual).

Exposure period: 4h	Observation at	No. of animals
		135M	136M	137M
1)     Erythema and eschar	60 min	0	0	0
	24 h	0	0	0
	48 h	0	0	0
	72 h	0	0	0
2)     Edema	60 min	0	0	0
	24 h	0	0	0
	48 h	0	0	0
	72 h	0	0	0

 

Interpretation of results:

GHS criteria not met

Remarks:

EU criteria.

Conclusions:

The acute dermal irritation study in New Zealand White rabbits treated with a single administration of test article Fosfomycin PEA salt (0.5 g/animal) has to be considered "non irritant" for the skin.

Executive summary:

The acute dermal irritation study in New Zealand White rabbits treated with a single administration of test article Fosfomycin PEA salt (0.5 g/animal) followed the EU Method B.4 and the OECD Guideline 404. 3 rabbits were used in the study. On the first one the test article was applied for an exposure period of 3 minutes and 1 hour with observation periods of 3 minutes and 1, 24, 48 and 72 hours. The three rabbits were exposed to the test article for 4 hours and observed at periods of 1, 24, 48 and 72 hours. The application areas were covered and the adjacent areas of untreated skin of each animal served as control for the test.

No untoward clinical signs or behavioural alterations were observed.

At the application site, no signs dermal irritancy were observed in any treated rabbit.

The test article Fosfomycin PEA salt, when administered by dermal route to rabbits under the experimental conditions adopted, has to be considered "NON IRRITANT" for the skin.

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed (not irritating)

Eye irritation

Link to relevant study records

Reference

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

Qualifier:

according to guideline

Guideline:

OECD Guideline 405 (Acute Eye Irritation / Corrosion)

Deviations:

no

GLP compliance:

yes

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.)

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.

Irritation parameter:

cornea opacity score

Basis:

animal #1

Time point:

other: 24-72 h

Score:

0

Max. score:

0

Irritation parameter:

iris score

Basis:

animal #1

Time point:

other: 24-72 h

Score:

0

Max. score:

0

Irritation parameter:

conjunctivae score

Remarks:

redness

Basis:

animal #1

Time point:

other: 24-72 h

Score:

0.33

Max. score:

1

Reversibility:

fully reversible

Irritation parameter:

chemosis score

Basis:

animal #1

Time point:

other: 24-72 h

Score:

0

Max. score:

0

Irritation parameter:

cornea opacity score

Basis:

animal #2

Time point:

other: 24-72 h

Score:

0

Max. score:

0

Irritation parameter:

iris score

Basis:

animal #2

Time point:

other: 24-72 h

Score:

0

Max. score:

0

Irritation parameter:

conjunctivae score

Remarks:

redness

Basis:

animal #2

Time point:

other: 24-72 h

Score:

0

Max. score:

0

Irritation parameter:

chemosis score

Basis:

animal #2

Time point:

other: 24-72 h

Score:

0

Max. score:

0

Irritation parameter:

cornea opacity score

Basis:

animal #3

Time point:

other: 24-72 h

Score:

0

Max. score:

0

Irritation parameter:

iris score

Basis:

animal #3

Time point:

other: 24-72 h

Score:

0

Max. score:

0

Irritation parameter:

conjunctivae score

Remarks:

redness

Basis:

animal #3

Time point:

other: 24-72 h

Score:

0

Max. score:

0

Irritation parameter:

chemosis score

Basis:

animal #3

Time point:

other: 24-72 h

Score:

0

Max. score:

0

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

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.

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed (not irritating)

Respiratory irritation

Endpoint conclusion

Endpoint conclusion:

no study available

Additional information

Skin irritation: Key study: Test method according to EU Method B.4 and OECD Guideline 404. GLP study. The acute dermal irritation study in New Zealand White rabbits treated with a single administration of test article Fosfomycin PEA salt (0.5 g/animal) has to be considered "non-irritant" for the skin.

Eye irritation: Key study: Test method according to OECD Guideline 404. GLP study. 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.

Justification for selection of skin irritation / corrosion endpoint:

Only one study available.

Justification for selection of eye irritation endpoint:

Only one study available.

Justification for classification or non-classification

Based on the available information on irritation, the substance is not classified for irritation/corrosion.