Iron(1+), chloro[dimethyl 9,9-dihydroxy-3-methyl-2,4-di(2-pyridinyl-kN)-7-[(2-pyridinyl-kN)methyl]-3,7-diazabicyclo[3.3.1]nonane-1,5-dicarboxylate-kN3,kN7]-, chloride

Skin irritation / corrosion

Administrative data

Endpoint:

skin irritation: in vivo

Type of information:

experimental study

Adequacy of study:

key study

Study period:

From 23 December 2003 to 05 April 2004

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

guideline study

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

2004

Report date:

2004

Materials and methods

Test guideline

Test guideline 1

Qualifier:

according to guideline

Guideline:

OECD Guideline 404 (Acute Dermal Irritation / Corrosion)

Deviations:

no

Test guideline 2

Qualifier:

according to guideline

Guideline:

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

GLP compliance:

yes (incl. QA statement)

Test material

Test material information

Constituent 1

Reference substance name:

1,5-dimethyl 3-methyl-9-oxo-2,4-bis(pyridin-2-yl)-7-[(pyridin-2-yl)methyl]-3,7-diazabicyclo[3.3.1]nonane-1,5-dicarboxylate dichloroiron hydrate

EC Number:

610-388-9

Cas Number:

478945-46-9

Molecular formula:

C28H31N5O6FeCl2

IUPAC Name:

1,5-dimethyl 3-methyl-9-oxo-2,4-bis(pyridin-2-yl)-7-[(pyridin-2-yl)methyl]-3,7-diazabicyclo[3.3.1]nonane-1,5-dicarboxylate dichloroiron hydrate

Test material form:

solid: particulate/powder

Specific details on test material used for the study:

SOURCE OF TEST MATERIAL
- Source and lot/batch No.of test material: provided by the sponsor, SEAC sample number S2539801
- Expiration date of the lot/batch: 1 January 2005
- Purity test date: The supporting data for purity of the test item was not made available at the time of issuing this report and hence this information has been excluded from the statement of compliance. However, the sponsor has adressed this in a GLP compliant study, SEAC Study Reference Number AC030449

STABILITY AND STORAGE CONDITIONS OF TEST MATERIAL
- Storage condition of test material: At room temperature (range of 20±3 deg celsius), protected from light.
- Stability under test conditions: Not specified
- Solubility and stability of the test substance in the solvent/vehicle: not specified

Test animals

Species:

rabbit

Strain:

New Zealand White

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Source: Elevage Scientifique des Dombes, Chatillon sur Chalaronne, France
- Age at study initiation: 11-12 weeks (male and female)
- Weight at study initiation: male 1994g, female 1: 2063g, female 2 : 2029g
- Housing: Individually in stainless steel cages equipped with feed
hoppers and drinking water bowls.
- Diet (e.g. ad libitum): Pelleted standard Provimi Kliba 3418 rabbit maintenance
diet ad libitum
- Water (e.g. ad libitum): Community tap water ad libitum
- Acclimation period: Under laboratory conditions after health examination. Only animals without any visual signs of illness were used for the study. From 06-JAN-2004 to 11-JAN-2004

ENVIRONMENTAL CONDITIONS
- Temperature (°C): room temperature 17-23 deg celsius
- Humidity (%): 30-70% relative humidity
- Air changes (per hr): 10-15 air changes per hour.
- Photoperiod (hrs dark / hrs light): light cycle of 12 hours light and 12 hours dark. Music was played during the daytime light period.

IN-LIFE DATES: From: 6 January 2004 To:15 January 2004

Test system

Type of coverage:

semiocclusive

Preparation of test site:

clipped

Vehicle:

water

Remarks:

purified water

Controls:

yes

yes, concurrent no treatment

Amount / concentration applied:

TEST MATERIAL
- Amount(s) applied (volume or weight with unit): 0.5g
- Concentration (if solution): 0.5g moistened in 0.1 mL of purified water

Duration of treatment / exposure:

4 hours

Observation period:

1 hour (for two animals), 24, 48 and 72 hours after patch
removal

Number of animals:

3

Details on study design:

TEST SITE
- Area of exposure: left flank
- % coverage: 4x4 cm : 16 cm2
- Type of wrap if used: The dressing was wrapped around the abdomen and anchored with tape. No more details

REMOVAL OF TEST SUBSTANCE
- Washing (if done): The skin was flushed with lukewarm tap water to clean the application site
- Time after start of exposure: 4 hours

OBSERVATION TIME POINTS
(indicate if minutes, hours or days) 1, 24, 48 and 72 hours after the removal of the dressing, gauze patch and test item.

SCORING SYSTEM:
- Method of calculation: Grading of Skin Reactions
ERYTHEMA AND ESCHAR FORMATION
No erythema ........................................................................................................................ 0
Very slight erythema............................................................................................................ 1
Well-defined erythema ........................................................................................................ 2
Moderate to severe erythema.............................................................................................. 3
Severe erythema (beet redness) or eschar
formation (injuries in depth preventing erythema) reading .................................................. 4
OEDEMA FORMATION
No oedema.......................................................................................................................... 0
Very slight oedema (barely perceptible) .............................................................................. 1
Slight oedema (edges of area well-defined by definite raising) ........................................... 2
Moderate oedema (edges raised approximately 1 mm)...................................................... 3
Severe oedema (raised more than 1 mm and extending beyond the area of exposure) .... 4

Results and discussion

In vivo

Results

Results 1

Irritation parameter:

erythema score

Basis:

mean

Time point:

24/48/72 h

Score:

0

Max. score:

0

Reversibility:

fully reversible

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:

0

Reversibility:

fully reversible

Remarks on result:

no indication of irritation

Irritant / corrosive response data:

The mean score was calculated across 3 scoring times (24, 48 and 72 hours after patch removal) for each animal for erythema/eschar grades and for oedema grades, separately. The mean erythema/eschar score and the mean oedema score were 0.00 for all three animals.Very slight erythema was observed in two animals at the 1-hour reading. No abnormal findings were observed on the treated skin of any animal 24 hours after treatment.
Neither alterations of the treated skin were observed nor were corrosive effects evident on the skin.

Any other information on results incl. tables

Table1 :Body weights of the rabbits

 

Body weight in grams
Animal No.	Sex	First Day of Acclimatization	Day of Treatment	Last Day of Observation
21	male	1994	2195	2219
22	female	2063	2046	2156
23	female	2029	2244	2315

 

TABLE 2: SKINIRRITATION SCORES - INDIVIDUAL VALUES

Animal Number	Sex	Evaluation Interval*	Erythema	Oedema
21 22 23	M FF	1 hour	1 1 0	0 0 0
21 22 23	M FF	24 hours	0 0 0	0 0 0
21 22 23	M FF	48 hours	0 0 0	0 0 0
21 22 23	M FF	72 hours	0 0 0	0 0 0

* Examinations were performed at the specified times after removal of the dressing.

 

 

 

Applicant's summary and conclusion

Interpretation of results:

GHS criteria not met

Conclusions:

Under experimental condition of the study, the test item did not induce significant or irreversible damage to the skin. Based upon the CLP criteria, STAINLESS E-700-2003 is considered to be “not irritating” to rabbit skin.

Executive summary:

The primary skin irritation potential of STAINLESS E-700-2003 was investigated according to OECD test guideline no. 404 and OECD GLP principle.

The test item was applied by topical semi-occlusive application of 0.5 g to the intact left flank of each of three young adult New Zealand White rabbits. The duration of treatment was four hours. The scoring of skin reactions was performed 1, 24, 48 and 72 hours after removal of the dressing. The mean score was calculated across 3 scoring times (24, 48 and 72 hours after patch removal) for each animal for erythema/eschar grades and for oedema grades, separately.

The mean erythema/eschar score and the mean oedema score were 0.00 for all three animals.

The application of STAINLESS E-700-2003 to the skin resulted in mild signs of irritation (very slight erythema), in two animals. This effect was reversible and was no longer evident 24 hours after treatment. The test item caused no staining of the treated skin. No corrosive effects were noted on the treated skin of any animal at any of the measuring intervals and no other clinical signs of test item related effects were observed.

Thus, the test item did not induce significant or irreversible damage to the skin. Based upon the CLP criteria, STAINLESS E-700-2003 is considered to be “not irritating” to rabbit skin.