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

Eye irritation

Administrative data

Endpoint:

eye irritation: in vivo

Type of information:

experimental study

Adequacy of study:

key study

Study period:

From 23 January 2004 to 26 May 2004

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

guideline study with acceptable restrictions

Remarks:

No certificate of analysis was provided, two animals were found dead after treatment, no conclusion can be made for this mortality. There were still two animals for examinatiuon but it was insufficient according OECD method.

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

2004

Report date:

2004

Materials and methods

Test guideline

Qualifier:

according to guideline

Guideline:

OECD Guideline 405 (Acute Eye Irritation / Corrosion)

Deviations:

yes

Remarks:

Two animals were found dead approximately 1 hour after treatment. Analysis was performed on only 2 animals which survived.

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: SEAC sample number S2539801, supplied by the sponsor
- Expiration date of the lot/batch: not specified
- Purity test date: not specified. 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 is 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 the light
- Stability under test conditions: no data

TREATMENT OF TEST MATERIAL PRIOR TO TESTING
The test item was weighed and applied undiluted as delivered by the sponsor.

Test animals / tissue source

Species:

rabbit

Strain:

New Zealand White

Remarks:

SPF

Details on test animals or tissues and environmental conditions:

TEST ANIMALS
- Source: Elevage Scientifique des Dombes, Chatillon sur Chalaronne, France
- Age at study initiation: 12-13 weeks (male) and 11-13 weeks (female)
- Weight at study initiation: 2032g to 2143g
- Housing: Individually in stainless steel equipped with feed hoppers and drinking water bowls. Wood blocks and haystick were provided for gnawing
- Diet (e.g. ad libitum): Pelleted standard Provimi Kliba 3418 rabbit maintenance diet ad libitum
- Water (e.g. ad libitum):Community tap water from Füllinsdorf, ad libitum
- Acclimation period: 6-7 Days under laboratory conditions after health examination

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 17-23 deg Celsius
- Humidity (%): 30-70%
- Air changes (per hr): 10-15 air changes per hour
- Photoperiod (hrs dark / hrs light): 12h/12h. Music was played during the daytime light period

IN-LIFE DATES: From: 27 January 2004 To: 2 March 20047

Test system

Vehicle:

unchanged (no vehicle)

Controls:

yes

yes, concurrent no treatment

Amount / concentration applied:

TEST MATERIAL
- Amount(s) applied (volume or weight with unit): 0.1 mL was used (equivalent to 0.03g of test item)
- Concentration (if solution): not applicable

Observation period (in vivo):

1, 24, 48, 72 hours

Number of animals or in vitro replicates:

Four rabbits were used (two were found dead)

Details on study design:

REMOVAL OF TEST SUBSTANCE
No removal of test substrance

SCORING SYSTEM: EEC Commission Directive 92/69/EEC, July 31, 1992 Grading of Ocular Lesions

TOOL USED TO ASSESS SCORE: Varta Cliptrix diagnostic lamp

Results and discussion

In vivo

Results

Results 1

Irritation parameter:

chemosis score

Basis:

mean

Time point:

24/48/72 h

Score:

0

Max. score:

4

Reversibility:

fully reversible within: 24 hrs

Remarks on result:

no indication of irritation

Results 2

Irritation parameter:

chemosis score

Basis:

mean

Time point:

other: 1 hour

Score:

1

Max. score:

4

Reversibility:

fully reversible within: 24 hrs

Results 3

Irritation parameter:

cornea opacity score

Basis:

mean

Time point:

24/48/72 h

Score:

0

Max. score:

4

Remarks on result:

no indication of irritation

Results 4

Irritation parameter:

cornea opacity score

Basis:

mean

Time point:

other: 1 hour

Score:

0.5

Max. score:

4

Reversibility:

fully reversible within: 1 hour

Remarks on result:

probability of weak irritation

Results 5

Irritation parameter:

iris score

Basis:

mean

Time point:

24/48/72 h

Score:

0

Max. score:

2

Reversibility:

fully reversible

Remarks on result:

no indication of irritation

Results 6

Irritation parameter:

conjunctivae score

Basis:

mean

Time point:

other: 1 hour

Score:

1

Max. score:

3

Reversibility:

fully reversible within: 24 hours

Results 7

Irritation parameter:

conjunctivae score

Basis:

mean

Time point:

24/48/72 h

Score:

0.17

Max. score:

3

Reversibility:

fully reversible within: 48 hrs

Irritant / corrosive response data:

In the two surviving rabbits (one male and one female), only the female showed ocular changes such as a slight opacity in the whole corneal area, a moderate redness of the conjunctivae and sclera was still observed at the 24 hours reading. These effects were reversible and were no longer evident 48 hours after treatment. In the second animal (male) no abnormal findings were noted, at any assessment times.

Other effects:

Two females treated in this study died after test item instillation. The first animal was found dead one hour after treatment and the second 40 minutes after treatment. They were necropsied. No clinical signs were observed immediately after the treatment. The animals were not continuously observed before the 1-hour reading as no death and no clinical signs were expected. No clinical signs were observed in the two surviving animals.

No staining of the treated eyes produced by the test item was observed

No corrosion of the cornea was obsrved at any reading times

No macroscopic finding were noted in the two surviving animal at the end of the study. Several pale foci were seen in the heart of the first female which was found dead. The lungs of additional female which was found dead (second animal) were dark red discolored.

Any other information on results incl. tables

Table 1summary of result

Bodyweight in grams
Animal	sex	evaluation interval	corneal opacity	area ofopacity	iris	redness	chemosis	sclera
24	M	1hour	0	0	0	0	0	0
25	F		1	4	0	2	2	2
24	M	24hours	0	0	0	0	0	0
25	F		0	0	0	1	0	1
24	M	48hours	0	0	0	0	0	0
25	F		0	0	0	0	0	0
24	M	72hours	0	0	0	0	0	0
25	F		0	0	0	0	0	0

 

Applicant's summary and conclusion

Interpretation of results:

GHS criteria not met

Conclusions:

Under the experimental conditions of the study, the registered item was not irritating for rabbit eyes. According to the CLP criteria, the substance Stainless E-700-2003 was not classified for eye irritation.

Executive summary:

The GLP compliant study was perfomed to assess the potential irritancy of the Stainless E-700 -2003 in rabbit according to OECD 405 method.

4 New Zealand rabbits were used. 0.1 mL of the registered substance (equivalent to 0.03g of substance) was applied on left eye of each rabbits. Clinical signs, irritation and macroscopic examinations were performed.

In the two surviving rabbits (one male and one female), only the female showed ocular changes such as a slight opacity in the whole corneal area, a moderate redness of the conjunctivae and sclera was still observed at the 24 hours reading. These effects were reversible and were no longer evident 48 hours after treatment. In the second animal (male) no abnormal findings were noted, at any assessment times.

Two females treated in this study died after test item instillation. The first animal was found dead one hour after treatment and the second 40 minutes after treatment. They were necropsied. No clinical signs were observed immediately after the treatment. The animals were not continuously observed before the 1-hour reading as no death and no clinical signs were expected. No clinical signs were observed in the two surviving animals.

Under the experimental conditions of the study, the registered item was not irritating for rabbit eyes. According to the CLP criteria, the substance Stainless E-700-2003 was not classified for eye irritation.