Ferrate(1-), [[N,N'-1,2-ethanediylbis[N-[[2-(hydroxy-.kappa.O)phenyl]methyl]glycinato-.kappa.N,.kappa.O]](4-)]-, sodium (1:1), (OC-6-13)-

Eye irritation

Administrative data

Endpoint:

eye irritation: in vivo

Type of information:

experimental study

Adequacy of study:

key study

Study period:

2008-07-15 to 2008-10-24

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

other: GLP guideline study

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

2008

Report date:

2008

Materials and methods

Test guideline

Test guideline 1

Qualifier:

according to guideline

Guideline:

OECD Guideline 405 (Acute Eye Irritation / Corrosion)

Deviations:

yes

Remarks:

changes in air humidity

Test guideline 2

Qualifier:

according to guideline

Guideline:

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

Deviations:

yes

Remarks:

changes in air humidity

Principles of method if other than guideline:

Few times during the entire experiment the relative air humidity was above 70%. It did not influence study course and results.
No other deviations from guideline / method were stated during the entire experiment.

GLP compliance:

yes (incl. QA statement)

Test material

Test material information

Constituent 1

Reference substance name:

iron(3+) sodium 2-({2-[(carboxylatomethyl)[(2-oxidophenyl)methyl]amino]ethyl}[(2-oxidophenyl)methyl]amino)acetate

EC Number:

700-327-5

Cas Number:

1061328-86-6

Molecular formula:

C20H20FeN2NaO6

IUPAC Name:

iron(3+) sodium 2-({2-[(carboxylatomethyl)[(2-oxidophenyl)methyl]amino]ethyl}[(2-oxidophenyl)methyl]amino)acetate

Details on test material:

- Name of test material (as cited in study report): Fe (III) HBED
- Substance type: chelate
- Physical state: microgranulate
- Analytical purity: 8.6% of Fe3+
- Impurities (identity and concentrations): no data
- Composition of test material, percentage of components: no data
Data concerning identity, purity and stability of test item are responsibility of Sponsor.
- Purity test date: 2008-05-26
- Lot/batch No.: 215/P/Fe-HBED
- Expiration date of the lot/batch: not reported
- Stability under test conditions: up to 15.05.2011
- Storage condition of test material: at temp. from -10°C to +30°C
- Other:

Test animals / tissue source

Species:

rabbit

Strain:

New Zealand White

Details on test animals or tissues and environmental conditions:

TEST ANIMALS
- Source: Reproductive Farm of Rabbits, Balice
- Age at study initiation: two 5-month-old (rabbit No 1 and No 3) and one 5.5-month-old (rabbit No 2).
- Weight at study initiation:the rabbit No 1 weighed 2.8 kg, rabbit No 2 – 3.0 kg and rabbit No 3 – 2.3 kg
- Housing: The animals were kept individually in metal cages with dimensions (length x width x height): 60 x 35 x 40 cm.
- Diet (e.g. ad libitum): ad libitum (standard granulated fodder "LSK" produced by Wytwórnia Koncentratów i Mieszanek Paszowych AGROPOL, Motycz)
- Water (e.g. ad libitum): ad libitum; tap water
- Acclimation period: 5 days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 20-22
- Humidity (%): 45-90
- Air changes (per hr): no data
- Photoperiod (hrs dark / hrs light): 12/12

IN-LIFE DATES: From: 2008-08-18 (rabbit No 1) and 2008-09-16 (rabbit No 2 and No 3) To: 2008-09-01 (rabbit No 1) and 2008-09-19 (rabbit No 2 and No 3).

Test system

Vehicle:

unchanged (no vehicle)

Remarks:

test material was dissolved in water

Controls:

no

Amount / concentration applied:

TEST MATERIAL
- Amount(s) applied (volume or weight with unit): 0.1 mL (0.042 g)

Duration of treatment / exposure:

single exposure

Observation period (in vivo):

Condition of cornea, iris and conjunctiva was evaluated after 1, 24, 48 and 72 hours as well as 7 and 14 days since administration of test item.

Number of animals or in vitro replicates:

3

Details on study design:

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

SCORING SYSTEM: The evaluation was performed according to the scoring system of OECD Guideline No 405 / Method B.5. (Annex 7).
Results of study were evaluated according to the Annex to Decree of Ministry of Health of September 2nd, 2003 (Acts Daily No 171, Position 1666).

TOOL USED TO ASSESS SCORE: no data

Results and discussion

In vivo

Results

Results 1

Irritation parameter:

cornea opacity score

Basis:

mean

Remarks:

of scores for 3 animals

Time point:

other: at 24, 48 and 72 hours

Score:

0

Max. score:

4

Remarks on result:

other: no effect

Results 2

Irritation parameter:

iris score

Basis:

mean

Remarks:

of scores for 3 animals

Time point:

other: at 24, 48 and 72 hours

Score:

0

Max. score:

2

Remarks on result:

other: no effect

Results 3

Irritation parameter:

conjunctivae score

Basis:

animal #1

Time point:

other: mean at 24, 48 and 72 hours

Score:

1.3

Max. score:

3

Reversibility:

fully reversible within: 14 days

Results 4

Irritation parameter:

conjunctivae score

Basis:

animal #2

Time point:

other: mean at 24, 48 and 72 hours

Score:

1

Max. score:

3

Reversibility:

fully reversible within: 72 hours

Results 5

Irritation parameter:

conjunctivae score

Basis:

animal #3

Time point:

other: mean at 24, 48 and 72 hours

Score:

0.7

Max. score:

3

Reversibility:

fully reversible within: 72 hours

Results 6

Irritation parameter:

chemosis score

Basis:

animal #1

Time point:

other: mean at 24, 48 and 72 hours

Score:

1

Max. score:

4

Reversibility:

fully reversible within: 7 days

Results 7

Irritation parameter:

chemosis score

Basis:

animal #2

Time point:

other: mean at 24, 48 and 72 hours

Score:

0.3

Max. score:

4

Reversibility:

fully reversible within: 48 hours

Results 8

Irritation parameter:

chemosis score

Basis:

animal #3

Time point:

other: mean at 24, 48 and 72 hours

Score:

0

Max. score:

4

Remarks on result:

other: no effect

Irritant / corrosive response data:

After administration of test item, pathological changes in iris and conjunctiva of rabbits’ eyes were stated. No pathological changes were stated in cornea. During reading after 1 hour since administration of test item, congestion of iris was stated in eyes of three rabbits, reaction of pupil to light was normal. Diffuse crimson redness (individual vessels hardly visible) was stated in conjunctivas of eyes of three rabbits. Furthermore, congestion of nictating membrane and circumcorneal injection were observed in rabbits. Swelling of conjunctiva, swelling of nictating membrane and excretion on lids, lids’ hair and considerable part of eye region were also stated in rabbits.
During reading after 24 hours since administration of test item, no pathological changes in irises of rabbits were stated. Diffuse crimson redness was still observed in conjunctivas of rabbit No 1 and No 2; congestion of some blood vessels was stated in conjunctiva of rabbit No 3. Congestion of nictating membrane was observed in three rabbits, circumcorneal injection was stated in rabbit No 2. Swelling of nictating membrane was observed in rabbits No 1 and No 2, slight swelling of conjunctiva was stated in rabbit No 1. No swelling of conjunctiva was stated in rabbit No 3. Excretion (on lids and lids’ hair) was stated only in rabbit No 2.
During reading after 48 hours since administration of test item, the following changes in conjunctivas were stated: erythema in form of congestion of some blood vessels and congestion of nictating membrane – in three rabbits; circumcorneal injection – in rabbit No 1. Slight swelling of conjunctiva and swelling of nictating membrane were stated in rabbit No 1. No swelling of conjunctiva and no excretion
were stated in rabbit No 2.
During reading after 72 hours since administration of test item, changes in conjunctiva were stated only in rabbit No 1. These were: erythema in form of congestion of some blood vessels, congestion of nictating membrane, circumcorneal injection and swelling of nictating membrane. No pathological changes were stated in rabbit No 2 and No 3.
During reading after 7 days since administration of test item, the following changes were observed in conjunctiva of rabbit No 1: erythema in form of congestion of some blood vessels, congestion of nictating membrane and circumcorneal injection. No swelling of conjunctiva was stated.
During reading after 14 days since administration of test item, no pathological changes were stated in eye of rabbit No 1.

Other effects:

Body weight of animals
At the start of experiment the rabbit No 1 weighed 2.8 kg, rabbit No 2 – 3.0 kg and rabbit No 3 – 2.3 kg. At the end of experiment rabbit No 1 weighed 2.9 kg, rabbit No 2 – 3.1 kg and rabbit No 3 – 2.8 kg.

Applicant's summary and conclusion

Interpretation of results:

not irritating

Remarks:

Migrated information Criteria used for interpretation of results: EU

Conclusions:

Mean scores calculated for each animal over 24, 48 and 72 hours were 1.0, 0.3 and 0.0 for chemosis, 1.3, 1.0 and 0.7 for redness of the conjunctiva, 0.0, 0.0 and 0.0 for iris lesions and 0.0, 0.0 and 0.0 for corneal opacity. The mean scores for 2 out of 3 animals do not exceed trigger values for classification and labelling defined in the CLP. The test substance Fe (III) HBED is considered to be not irritating to eyes.

Executive summary:

Acute eye irritation/corrosion study with Fe (III) HBED according to the OECD TG 405 was conducted in New Zealand White rabbits (Gruszka, 2008). The test item in amount of 0.042 g (volume of 0.1 mL) was administered to conjunctival sack of one eye of each rabbit. The second eye served as control. Condition of cornea, iris and conjunctiva was evaluated after 1, 24, 48 and 72 hours as well as 7 and 14 days since administration of test item. The mean values of the scores for chemosis, redness of the conjunctiva, iris lesions and corneal opacity were calculated for each animal. The interpretation of results was carried out according to the classification criteria laid down in the Regulation (EC) No. 1272/2008 (CLP). After administration of test item, changes in iris and conjunctiva of rabbits’ eyes were observed during readings. No pathological changes were stated in cornea of all animals at all reading time points. At 1-hour reading, congestion of iris was observed in eyes of three rabbits, but reaction of pupil to light was normal. No lesions in iris of all animals were observed at further evaluation time points. The highest conjunctivae score of 2 (diffuse crimson redness (individual vessels were hardly visible)) was noted in three animals at 1 hour reading and was still present in two animals after 24-hour reading. Conjunctival reaction in form of congestion of some blood vessels and congestion of nictating membrane were present in three rabbits at 48-hour reading. These effects were fully reversible within 72 hours after treatment in two rabbits and on the day 14 in the third rabbit. Furthermore, congestion of nictating membrane, circumcorneal injection, swelling of conjunctiva, swelling of nictating membrane and excretion on lids, lids’ hair and considerable part of eye region were observed in all rabbits (score of 1 at 1-hour and at 24-hour reading). Circumcorneal injection and slight swelling of conjunctiva and swelling of nictating membrane remained until 72-hour reading in one rabbit, while no effects were seen anymore in another rabbits.

Mean scores calculated for each animal over 24, 48 and 72 hours were 1.0, 0.3 and 0.0 for chemosis, 1.3, 1.0 and 0.7 for redness of the conjunctiva, 0.0, 0.0 and 0.0 for iris lesions and 0.0, 0.0 and 0.0 for corneal opacity. The mean scores for 2 out of 3 animals do not exceed trigger values for classification and labelling defined in the CLP. The test substance Fe (III) HBED is considered to be not irritating to eyes.