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Toxicological information

Skin irritation / corrosion

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Administrative data

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

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
1994
Report date:
1994

Materials and methods

Test guidelineopen allclose all
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

Test material

Constituent 1
Chemical structure
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
Test material form:
solid: particulate/powder
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

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)

Test system

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

Results and discussion

In vivo

Resultsopen allclose all
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

Any other information on results incl. tables

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

 

Applicant's summary and conclusion

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.