Reaction mass of iron chelate of sodium salt N-[1,2 dicarboxyethyl] D,L aspartic acid and sodium chloride

Eye irritation

Administrative data

Endpoint:

eye irritation: in vivo

Type of information:

experimental study

Adequacy of study:

key study

Study period:

23 of May till 27 of June 2007

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

other: GLP guideline study

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

2007

Report date:

2007

Materials and methods

Test guideline

Test guideline 1

Qualifier:

according to guideline

Guideline:

EU Method B.5 (Acute Toxicity: Eye Irritation / Corrosion)

Test guideline 2

Qualifier:

according to guideline

Guideline:

OECD Guideline 405 (Acute Eye Irritation / Corrosion)

GLP compliance:

yes (incl. QA statement)

Test material

Test material information

Constituent 1

Reference substance name:

Fe(III)IDHA

IUPAC Name:

Fe(III)IDHA

Constituent 2

Reference substance name:

666828-40-6

Cas Number:

666828-40-6

IUPAC Name:

666828-40-6

Test material form:

other: microgranules

Details on test material:

- Substance type: chelate
- Physical state: green microgranules

Test animals / tissue source

Species:

rabbit

Strain:

New Zealand White

Details on test animals or tissues and environmental conditions:

TEST ANIMALS
- Source: conventional Reproductive Farm of Rabbits, Balice
- Age at study initiation: 6-month-old
- Weight at study initiation: 3,60 kg
- Housing:
- Diet (e.g. ad libitum): standard granulated fodder "LSK" produced by Wytwórnia Koncentratów i Mieszanek Paszowych AGROPOL, Motycz
- Water (e.g. ad libitum): tap water
- Acclimation period: 5 days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 21 – 22
- Humidity (%): 52 - 70% (few times above 70%);
- Photoperiod (hrs dark / hrs light): artificial fluorescent lighting: 12 hours light / 12 hours darkness

The animals were kept individually in metal cages with dimensions: 60 x 35 x 40 cm. Each cage was equipped with label containing information on study code, start date of the experiment, sex and animal numbers.

IN-LIFE DATES: The test material was administered to rabbits’ eyes on: 31.05.2007 (rabbit No 1) and 04.06.2007 (rabbits No 2 and 3). The experiment was terminated on 07.06.2007 (rabbit No 1 and 2) and 14.06.2007 (rabbit No 3).

Test system

Vehicle:

unchanged (no vehicle)

Controls:

other: The second eye was used as the control one.

Amount / concentration applied:

TEST MATERIAL
- Amount(s) applied (volume or weight with unit): 0.1 g of unchanged test substance as a single
- Concentration (if solution): not applied

Duration of treatment / exposure:

single administration

Observation period (in vivo):

After 1, 24, 48,72 hours and 7 days since administration of the test material condition
of cornea, iris and conjunctiva was evaluated.

Number of animals or in vitro replicates:

3

Details on study design:

The test material in form of powder was administered in amount of 0,1 g as a single dose to conjunctival sack of one eye to one rabbit (rabbit No 1), by gentle distraction of lower eyelid. Then both eyelids were kept together for a moment to protect loosing of the test material. The second eye was used as the control one. Following evaluation of the treated eye, in order to confirm the obtained results, the test material was administered in the same way to rabbits No 2 and 3.

REMOVAL OF TEST SUBSTANCE
- Washing (if done): no

SCORING SYSTEM: classification on the basis of OECD Guideline No 405 / EU Method B.5
Cornea
Opacity: degree of density (readings should be taken from most dense area) *
- No ulceration or opacity: 0
- Scattered or diffuse areas of opacity (other than slight dulling of normal lustre), 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
Maximum possible: 4
* The area of corneal opacity should be noted
Iris:
- Normal: 0
- Markedly deepened rugae, congestion, swelling, moderate circumcorneal hyperaemia or injection, iris reactive to light (a sluggish reaction is considered to be an effect): 1
- Hemorrhage, gross destruction, or no reaction to light: 2
Maximum possible: 2
Conjunctivae:
Redness (refers to palpebral and bulbar conjunctivae, excluding cornea and iris)
- Normal: 0
- Some blood vessels hyperaemic (injected): 1
- Diffuse, crimson colour, individual vessels not easily discernible: 2
- Diffuse beefy red: 3
Maximum possible: 3

Chemosis:
Swelling (refers to lids and/or nictating membranes)
- Normal: 0
- Some swelling above normal: 1
- Obvious swelling, with partial eversion of lids: 2
- Swelling, with lids about half closed: 3
- Swelling, with lids more than half closed: 4
Maximum posible: 4

TOOL USED TO ASSESS SCORE: not recorded

Results and discussion

In vivo

Results

Results 1

Irritation parameter:

conjunctivae score

Remarks:

erythema

Basis:

animal #1

Time point:

other: average after 24 - 72 h

Score:

1.7

Max. score:

2

Reversibility:

fully reversible within: 7 days

Results 2

Irritation parameter:

conjunctivae score

Remarks:

oedema

Basis:

animal #1

Time point:

other: average after 24- 72h

Score:

1

Max. score:

2

Reversibility:

fully reversible within: 7 days

Results 3

Irritation parameter:

conjunctivae score

Remarks:

erythema

Basis:

animal #2

Time point:

other: average after 24-72 h

Score:

1

Max. score:

2

Reversibility:

fully reversible within: 48h

Results 4

Irritation parameter:

conjunctivae score

Remarks:

oedema

Basis:

animal #2

Time point:

other: average after 24-72 h

Score:

0.3

Max. score:

2

Reversibility:

fully reversible within: 48h

Results 5

Irritation parameter:

conjunctivae score

Remarks:

erythema

Basis:

animal #3

Time point:

other: average after 24-72 h

Score:

1

Max. score:

2

Reversibility:

fully reversible within: 7 days

Results 6

Irritation parameter:

conjunctivae score

Remarks:

oedema

Basis:

animal #3

Time point:

other: average after 24-72h

Score:

0.3

Max. score:

1

Reversibility:

fully reversible within: 48h

Irritant / corrosive response data:

During observations only changes in eye conjunctiva were stated. During evaluation after 1 hour since the test material administration, all rabbits showed erythema of eye conjunctiva – in form of diffuse crimson redness, congestion of third eyelid and circumcorneal injections. Rabbits No 1 and 3 showed slight
oedema while rabbit No 2 distinct oedema with partial eversion of eyelids. Additionally all rabbits showed oedema of third eyelid and excretion – on eyelids and
eyelids hair in rabbits no 1 and 2 and slight amount of excretion in rabbit No 3.
During evaluation after 24 hours since the administration, all rabbits showed congestion of third eyelid, circumcorneal injection and erythema of eye conjunctiva – in form of diffuse crimson redness in rabbits No 1 and 2 and in form of blood vessels hyperaemia (injection) in rabbit No 3. In all rabbits slight oedema of third eyelid was stated. Additionally all rabbits showed excretion – on eyelids and eyelids hair in rabbit No 1 and slight amount of excretion in rabbits No 2 and 3.
During observation after 48 hours since administration, all rabbits showed erythema – in form of diffuse crimson redness in rabbit No 1 and in form of blood vessels congestion (injection) in rabbits No 2 and 3. Additionally rabbit No 1 showed circumcorneal injection, oedema of third eyelid and excretion on eyelids and eyelids hair.
During evaluation after 72 hours since administration rabbits No 1 and 3 showed erythema in form of blood vessels congestion (injection) and congestion of third eyelid. Additionally rabbit No 1 showed circumcorneal injection, oedema of third eyelid and excretion on eyelids and eyelids hair. Rabbit No 2 showed no pathological changes.
During evaluation after 7 days since administration no pathological changes were stated in eyes of rabbits No 1 and 3.

Other effects:

At the start of the experiment the rabbits weighed: 3,73 kg (rabbit No 1), 3,56 kg (rabbit No 2) and 3,52 kg (rabbit No 3). At the end of the test body weight of rabbits amounted appropriately: 3,84 kg; 3,60 kg and 3,54 kg.

Any other information on results incl. tables

Chelate with name: Fe (III) IDHA - Point evaluation of acute eye irritation/corrosion study for rabbits

Rabbit No	Part of eye		Evaluation after					Average of evaluation after 24, 48 and 72 h
			1h	24h	48h	72h	7 days
1	cornea		0	0	0	0	0	0
	Iris		0	0	0	0	0	0
	conjunctiva	erythema	2	2	2	1	0
		oedema	1	1	1	1	0
2	cornea		0	0	0	0	-	0
	Iris		0	0	0	0	-	0
	conjunctiva	erythema	2	2	1	0	-
		oedema	2	1	0	0	-
3	cornea		0	0	0	0	0	0
	Iris		0	0	0	0	0	0
	conjunctiva	erythema	2	1	1	1	0
		oedema	1	1	0	0	0

Applicant's summary and conclusion

Interpretation of results:

not irritating

Remarks:

Migrated information Criteria used for interpretation of results: EU

Conclusions:

Fe (III) IDHA does not irritate eyes of the rabbits.

Executive summary:

Acute eye irritation/corrosion study of Chelate with name: Fe (III) IDHA for rabbits was performed according to OECD Guideline for Testing of Chemicals No 405/Method B.5. as well as Principles of Good Laboratory Practice (GLP - OECD,1997).

The study was performed with three white rabbits of New Zealand strain. The test material in form of powder was administered in amount of 0.1 g to conjunctival sack of one eye to each rabbit. After 1, 24, 48, 72 hours and 7 days since administration of

the test material, condition of cornea, iris and conjunctiva was evaluated. During evaluation after 1, 24, 48 and 72 the test rabbits showed changes in form of erythema and oedema of eye conjunctiva.

Classification of the test material was performed according to Regulation 1272/2008. Taking into account the obtained results, one may state that Chelate with name: Fe (III) IDHA does not irritate eyes of rabbits.