Bis(5-oxo-L-prolinato-N1,O2)zinc

Skin irritation / corrosion

Administrative data

Endpoint:

skin irritation: in vivo

Type of information:

experimental study

Adequacy of study:

key study

Study period:

09 April 2003 to 02 June 2003

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

guideline study with acceptable restrictions

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

2003

Report date:

2008

Materials and methods

Test guideline

Qualifier:

according to guideline

Guideline:

OECD Guideline 404 (Acute Dermal Irritation / Corrosion)

GLP compliance:

not specified

Test material

Test material information

Constituent 1

Reference substance name:

Bis(5-oxo-L-prolinato-N1,O2)zinc

EC Number:

239-473-5

EC Name:

Bis(5-oxo-L-prolinato-N1,O2)zinc

Cas Number:

15454-75-8

Molecular formula:

C10H12N2O6Zn

IUPAC Name:

(3'aR)-3,3',6,6'-tetraoxo-3a,3'a,4,4',5,5',6,6'-octahydro-3H,3'H-1,1'-spirobi[pyrrolo[1,2-c]1-oxa-3-aza-2-zincacyclopentane]-1,1-bis(ylium)-2,2'-diuide

Test material form:

solid: particulate/powder

Remarks:

migrated information: powder

Details on test material:

- Appearance: Powder
- Storage condition of test material: At room temperature, light shielding

Test animals

Species:

rabbit

Strain:

New Zealand White

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Weight at study initiation: 2.8 - 4.4 kg
- Housing: Bracket cages with 1 animal/cage.
- Diet: Each animal was limited to 150 g of feed per day.
- Water: Tap water ad libitum
- Acclimation period: Not specified, but healthy rabbits without island skin were selected.

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 23 ± 3 °C
- Humidity (%): 50 ± 20 %
- Air changes (per hr): All-fresh ventilation of 10 to 15 cycles per hour.
- Photoperiod (hrs dark / hrs light): 12 hours from 7 am to 7 pm; between 200 and 600 lux.

Test system

Type of coverage:

semiocclusive

Preparation of test site:

clipped

Vehicle:

water

Controls:

no

Amount / concentration applied:

TEST MATERIAL
- Amount applied: 0.5 g
- Concentration: The test item was prepared as a paste of the maximum concentration (68 %) by adding distilled water at room temperature.

Duration of treatment / exposure:

4 hours

Observation period:

1 week

Number of animals:

3

Details on study design:

TEST SITE
- Area of exposure: In order to eliminate bias based on the application site, the patch was applied to different locations for each animal.
- Type of wrap if used: Patches were created by placing cotton lint sized 2.5 cm x 2.5 cm on surgical tape. 0.5 g of the test article was placed on the cloth. The patches were applied to the skin on the clipped site of the animals, and fixed into place using stretchable adhesive tape. The patches were covered occlusively for 4 hours.

REMOVAL OF TEST SUBSTANCE
- Washing: the tape and patch were removed, and the test article was removed from the application area using wet paper towels.
- Time after start of exposure: Four hours after application.

OBSERVATION TIME POINTS
An observation of the application site was made 1 hour after removing the patch.
General observation of symptoms: Observations were conducted once a day, with the exception of holidays, for all animals.
Measurement of body weight: The body weight of all of the animals was measured on the day of treatment and during each reading.

SCORING SYSTEM
- Method of calculation:
A. Erythema and eschar formation
0 - No erythema
1 - Very slight erythema (barely perceptible)
2 - Well-defined erythema
3 - Moderate to severe erythema
4 - Severe erythema (beet red) or eschar formation preventing grading of erythema (lesion in deep area)

B. Oedema formation
0 - No oedema
1 - Very slight oedema (barely perceptible)
2 - Slight oedema (edges of area well defined by definite raising)
3 - Moderate oedema (raised approximately 1 mm)
4vSevere oedema (raised more than 1 mm and extending beyond area of exposure)

Observations for changes in scaling, coloration, and corrosion were also conducted.

Results and discussion

In vivo

Results

Results 1

Irritation parameter:

erythema score

Basis:

mean

Time point:

24/48/72 h

Score:

0

Max. score:

4

Reversibility:

other: Not applicable

Remarks on result:

no indication of irritation

Results 2

Irritation parameter:

edema score

Basis:

mean

Time point:

24/48/72 h

Score:

0

Max. score:

4

Reversibility:

other: Not applicable

Remarks on result:

no indication of irritation

Irritant / corrosive response data:

Skin irritation
For the 68 % of the test material paste, very slight erythema was observed one hour after after removing the patch in 1/3 of the animals, and skin irritation disappeared 24 hours after removal of the patch. There were no changes observed afterwards in the week after removal of the patch.

Other effects:

General observation of symptoms
During the study period, there were no abnormalities in clinical signs observed.

Measurement of body weight
During the study period, there were no significant changes in body weight.

Any other information on results incl. tables

Table 1: Skin Irritation Scores of the Test Material

Reading Time (Hours)	Animal No.	Erythema	Oedema	Mean Score
				Erythema	Oedema	Total
1	00101 00102 00103	0 1 0	0 0 0	0.3	0.0	0.3
24	00101 00102 00103	0 0 0	0 0 0	0.0	0.0	0.0
48	00101 00102 00103	0 0 0	0 0 0	0.0	0.0	0.0
72	00101 00102 00103	0 0 0	0 0 0	0.0	0.0	0.0
1 week	00101 00102 00103	0 0 0	0 0 0	0.0	0.0	0.0

Applicant's summary and conclusion

Interpretation of results:

other: Not classified according to EU critera.

Conclusions:

Under the conditions of this study, it was concluded that the test material was not irritating.

Executive summary:

The skin irritation potential of the test material was investigated in a study which was conducted in accordance with the standardised guidelines OECD 404 (Acute Dermal Irritation/ Corrosion). The study was conducted in accordance with generally accepted scientific principles, possibly with incomplete reporting or methodological deficiencies, which do not affect the quality of the relevant results.

During the study, animal was kept individually in each cage, and a card indicating the protocol number, animal number, and the name and concentration of the test article was attached to each of the cages. In addition, mix-ups between the animals were prevented, by refraining from opening 2 cages at the same time. The animals were treated with the 0.5 g test material via semi-occlusive adhesion. Patches were created by placing cotton lint sized 2.5 cm x 2.5 cm on surgical tape. 0.5 g of the test article was placed on the cloth. The patches were applied to the skin on the clipped site of the animals, and fixed into place using stretchable adhesive tape. The patches were covered occlusively for 4 hours. In order to eliminate bias based on the application site, the patch was applied to different locations for each animal. Four hours after application, the tape and patch were removed, and the test article was removed from the application area using wet paper towels.

For the 68 % test material paste, very slight erythema was observed one hour after after removing the patch in 1/3 of the animals, and skin irritation disappeared 24 hours after removal of the patch. There were no changes observed afterwards in the week after removal of the patch.

Under the conditions of the study, the test material was determined to be not irritating.