Sodium [[α,α'-(ethylenediimino)bis[2-hydroxybenzene-1-acetato]](4-)]ferrate(1-)

Endpoint summary

Description of key information

Skin irritation

Two acute skin irritation/corrosion studies in albino rabbits to determine whether irritant or corrosive potency exists for the structural analogue test substance Fe(Na)EDDHA (CAS 84539-55-9) (CIBA-GEIGY, 1993c, Report No. 931143; Mercier, 1992, Report No. 209306). These tests were based on the OECD Guideline 404 (Acute Dermal Irritation/Corrosion) and were performed on 3 rabbits, checked for normal skin conditions. A gauze patch bearing 0.5 g of the test article was applied to the right flank of each animal and held in place for 4 hours by an adhesive tape. The studies showed that Fe(Na)EDDHA does not cause skin irritation, as the mean values of the recordings 24 to 72 hours after application were scored 0 in the study performed by CIBA-GEIGY (1993) and the scores determined in the study of Mercier (1992) were all below the trigger values for classification as skin irritant.

Eye irritation

Two eye irritation studies were performed according to OECD Guideline 405 (Acute Eye Irritation/Corrosion) with the read-across test item Fe(Na)EDDHA (CAS 84539-55-9) (CIBA-GEIGY, 1993d; Report No. 931144; Mercier, 1992, Report No. 209305). The tests were performed on 3 New Zealand White rabbits. A volume of 0.1 mL of the test item was placed into the conjunctival sac of the left eye of each animal. The lids were then held together for about one second in order to prevent loss of the test article. The animals were checked daily for systemic symptoms and mortality. The studies showed that the test substance does not cause eye irritation as none of the animals achieved a mean score leading to classification according to GHS (>= 1 for cornea and iris; >= 2 for redness and chemosis).

Key value for chemical safety assessment

Skin irritation / corrosion

Link to relevant study records

Reference

Reference 1

Endpoint:

skin irritation: in vivo

Type of information:

experimental study

Adequacy of study:

key study

Study period:

1992

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

guideline study

Qualifier:

according to guideline

Guideline:

OECD Guideline 404 (Acute Dermal Irritation / Corrosion)

Deviations:

no

GLP compliance:

yes

Species:

rabbit

Strain:

New Zealand White

Details on test animals or test system and environmental conditions:

No details available

Type of coverage:

semiocclusive

Preparation of test site:

shaved

Vehicle:

water

Controls:

no

Amount / concentration applied:

- Amount applied: 0.5 g test article moistened with 0.18 g of purified water

Duration of treatment / exposure:

4 hours

Observation period:

1, 24, 48, 72 hours after removal of the bandage as well as day 7 and 14

Number of animals:

3

Details on study design:

No details available

Irritation parameter:

erythema score

Basis:

animal #1

Time point:

other: 24+48+72 hours

Score:

1.33

Max. score:

4

Reversibility:

fully reversible

Irritation parameter:

edema score

Basis:

animal #1

Time point:

other: 24+48+72 hours

Score:

0

Max. score:

4

Irritation parameter:

erythema score

Basis:

animal #2

Time point:

other: 24+48+72 hours

Score:

1.33

Max. score:

4

Reversibility:

fully reversible

Irritation parameter:

edema score

Basis:

animal #2

Time point:

other: 24+48+72 hours

Score:

0.33

Max. score:

4

Reversibility:

fully reversible

Irritation parameter:

erythema score

Basis:

animal #3

Time point:

other: 24+48+72 hours

Score:

1.33

Max. score:

4

Reversibility:

fully reversible

Irritation parameter:

edema score

Basis:

animal #3

Time point:

other: 24+48+72 hours

Score:

0.33

Max. score:

4

Reversibility:

fully reversible

Irritant / corrosive response data:

The observed skin reactions were fully reversible within 14 days.

Other effects:

No other effects were observed.

Table: Individual scores.

	time	animal 1	animal 2	animal 3
erythema	1 h	2	2	2
	24 h	2	2	2
	48 h	1	1	1
	72 h	1	1	1
	7 d	0	1	1
	14 d	0	0	0
edema	1 h	1	0	1
	24 h	0	1	1
	48 h	0	0	0
	72 h	0	0	0
	7 d	0	0	0
	14 d	0	0	0

Interpretation of results:

not irritating

Remarks:

Migrated information Criteria used for interpretation of results: OECD GHS

Conclusions:

Application of this test article to the rabbit skin can be designated as not irritating.

Executive summary:

Skin irritation potential of FeNaEDDHA was evaluated in a skin irritation study according to the OECD guideline 404. 3 New Zealand White rabbits were exposed dermally to the test article for 4 hours under semiocclusive condition. The skin reactions were examined 1, 24, 48 and 72 hours after removal of bandage as well as on day 7 and 14. Erythema and oedema observed in treated animals were fully reversible within 14 days.

The test material can be considered as not irritating to skin since the mean scores in treated animals are all below the trigger values defined in the EU CLP (Regulation (EC) No. 1272/2008) for classification as skin irritant.

Reference 2

Endpoint:

skin irritation: in vivo

Type of information:

experimental study

Adequacy of study:

supporting study

Study period:

1993-09-13 to 1993-09-24

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

guideline study

Qualifier:

according to guideline

Guideline:

OECD Guideline 404 (Acute Dermal Irritation / Corrosion)

Version / remarks:

1981

Deviations:

no

GLP compliance:

yes

Species:

rabbit

Strain:

New Zealand White

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Source: Dr. K. Thomae GmbH, Chemisch-pharmazeutische Fabrik, D-7950 Biberach/Riss
- Weight at study initiation: 2270 zo 2340 g
- Housing: individually in metal cages
- Diet (e.g. ad libitum):ad libitum, standard rabbit pellet-Nafag No.814
- Water (e.g. ad libitum):ad libitum, fresh water
- Acclimation period: at least 5 days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 20 +/- 3 degree C
- Humidity (%): 30 - 70 %
- Photoperiod (hrs dark / hrs light): 12 hours light cycle

Type of coverage:

occlusive

Preparation of test site:

shaved

Vehicle:

unchanged (no vehicle)

Controls:

other: a control gauze patch was applied to the contrlateral flank

Amount / concentration applied:

TEST MATERIAL
- Amount(s) applied (volume or weight with unit): 0.5 g of the test article moistened with distilled water

Duration of treatment / exposure:

4 h

Observation period:

The animals were checked daily for systemic symptoms and mortality. The skin reactions were evaluated 1, 24, 48, and 72 hours after removing the gauze patches.

Number of animals:

3 males

Details on study design:

TEST SITE
- Area of exposure: 6 cm²
- % coverage: 12-16 cm²
- Type of wrap if used: Isoplast (Isoplast AG, CH-5200 Brugg).
An area of at least 36 cm² was shaved on both flanksof the animals approximately 24 hours before treatment. Agauze patch (approx. 12-16 cm² bearing 0.5 g of the test article was apllied to the right flank of each animal. The skin area exposed directly to the test article was approx. 6 cm². A control gauze patch was applied to the contralateral flank. Before application both patches were moistened with distilled water. The patches were loosely covered with an aluminium foil (approx. 36 cm²) and held in place for 4 hours by an adhesive tape.

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

SCORING SYSTEM: OECD scoring system (documented in the OECD guideline 404)

Irritation parameter:

erythema score

Basis:

mean

Time point:

other: 24, 48, 72 h

Score:

0

Max. score:

4

Irritation parameter:

edema score

Basis:

mean

Time point:

other: 24, 48, 72 h

Score:

0

Max. score:

4

Irritant / corrosive response data:

No erythema or oedema were noted in treated animals at 24, 48 and 72-h observation time point.

Other effects:

One hour after removing the bandages a possible erythema reaction in two animal could not be evaluated because of brown staining, test article related.

Individual skin reaction scores
	ERYTHEMA			EDEMA
animal no.	624/MCF/TF	622/MCF/TF	362/M CF/TF	624/MCF/TF	622/MCF/TF	362/MCF/TF
after 1 hr. after 24 hrs. after 48 hrs. after 72 hrs.	0/0 0/0 0/0 0/0	0/* 0/0 0/0 0/0	0/* 0/0 0/0 0/0	0/0 0/0 0/0 0/0	0/0 0/0 0/0 0/0	0/0 0/0 0/0 0/0
mean 24-72 hrs	0/0	0/0	0/0	0/0	0/0	0/0

CF = control flank

TF = test flank

M = male

* = erythema not evaluable because of brown staining (substance related)

Interpretation of results:

not irritating

Remarks:

Migrated information Criteria used for interpretation of results: OECD GHS

Conclusions:

Application of FeNAEDDHA to the rabbit skin can be designated as not irritating.

Executive summary:

An acute skin irritation/corrosion study in albino rabbits was performed to determine the irritant or corrosive potency of FeNaEDDHA on the albino rat skin. This test was based on the OECD Guideline No. 404 (Acute Dermal Irritation/ Corrosion) and was performed on 3 male rabbits, checked for normal skin conditions. A gauze patch bearing 0.5 g of the test article was applied to the right flank of each animal and held in place for 4 hours by an adhesive tape. Because the mean values of the recordings 24 to 72 hours after application are scored 0, the test item FeNaEDDHA can be classified as non-irritant according to the GHS Regulation (EC) No. 1272/2008.

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed (not irritating)

Eye irritation

Link to relevant study records

Reference

Reference 1

Endpoint:

eye irritation: in vivo

Type of information:

experimental study

Adequacy of study:

key study

Study period:

1992

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

guideline study

Qualifier:

according to guideline

Guideline:

OECD Guideline 405 (Acute Eye Irritation / Corrosion)

Deviations:

no

GLP compliance:

yes

Species:

rabbit

Strain:

New Zealand White

Details on test animals or tissues and environmental conditions:

No details are available

Vehicle:

unchanged (no vehicle)

Controls:

no

Amount / concentration applied:

- Amount applied: 69 mg (quantity corresponding to a volume of 0,1 mL)

Duration of treatment / exposure:

Single exposure

Observation period (in vivo):

1, 24, 48, 72 hours; to reveal a possible reversibility, readings were continued on Day 7.

Number of animals or in vitro replicates:

3

Irritation parameter:

cornea opacity score

Basis:

animal #1

Time point:

other: 24+48+72 hours

Score:

0.6

Max. score:

4

Reversibility:

not fully reversible within: 7 days

Irritation parameter:

cornea opacity score

Basis:

animal #2

Time point:

other: 24+48+72 hours

Score:

0

Max. score:

4

Reversibility:

fully reversible

Irritation parameter:

cornea opacity score

Basis:

animal #3

Time point:

other: 24+48+72 hours

Score:

0

Max. score:

4

Reversibility:

fully reversible

Irritation parameter:

cornea opacity score

Basis:

mean

Time point:

other: 24+48+72 hours

Score:

0.22

Max. score:

4

Reversibility:

fully reversible within: 7 days

Irritation parameter:

iris score

Basis:

animal #1

Time point:

other: 24+48+72 hours

Score:

1

Max. score:

2

Reversibility:

fully reversible within: 7 days

Irritation parameter:

iris score

Basis:

animal #2

Time point:

other: 24+48+72 hours

Score:

0.33

Max. score:

2

Reversibility:

fully reversible within: 7 days

Irritation parameter:

iris score

Basis:

animal #3

Time point:

other: 24+48+72 hours

Score:

0.33

Max. score:

2

Reversibility:

fully reversible within: 7 days

Irritation parameter:

iris score

Basis:

mean

Time point:

other: 24+48+72 hours

Score:

0.55

Max. score:

2

Reversibility:

fully reversible within: 7 days

Irritation parameter:

conjunctivae score

Basis:

animal #1

Time point:

other: 24+48+72 hours

Score:

0.33

Max. score:

3

Reversibility:

fully reversible within: 7 days

Irritation parameter:

conjunctivae score

Basis:

animal #2

Time point:

other: 24+48+72 hours

Score:

0.33

Max. score:

3

Reversibility:

fully reversible within: 7 days

Irritation parameter:

conjunctivae score

Basis:

animal #3

Time point:

other: 24+48+72 hours

Score:

0.33

Max. score:

3

Reversibility:

not fully reversible within: 7 days

Irritation parameter:

conjunctivae score

Basis:

mean

Time point:

other: 24+48+72 hours

Score:

0.33

Max. score:

3

Reversibility:

fully reversible within: 7 days

Irritation parameter:

chemosis score

Basis:

animal #1

Time point:

other: 24+48+72 hours

Score:

0.33

Max. score:

4

Reversibility:

fully reversible within: 7 days

Irritation parameter:

chemosis score

Basis:

animal #2

Time point:

other: 24+48+72 hours

Score:

0.33

Max. score:

4

Reversibility:

fully reversible within: 7 days

Irritation parameter:

chemosis score

Basis:

animal #3

Time point:

other: 24+48+72 hours

Score:

0.33

Max. score:

4

Reversibility:

fully reversible within: 7 days

Irritation parameter:

chemosis score

Basis:

mean

Time point:

other: 24+48+72 hours

Score:

0.33

Max. score:

4

Reversibility:

fully reversible within: 7 days

Irritant / corrosive response data:

No further data available

Other effects:

No other effects were noted

	time	animal 1	animal 2	animal 3
corneal opacity	24 h	2	0	0
	48 h	0	0	0
	72 h	0	0	0
iris	24 h	1	1	1
	48 h	1	0	0
	72 h	1	0	0
conjunctivae	24 h	1	1	1
	48 h	0	0	0
	72 h	0	0	0
chemosis	24 h	1	1	1
	48 h	0	0	0
	72 h	0	0	0

Interpretation of results:

not irritating

Remarks:

Migrated information Criteria used for interpretation of results: OECD GHS

Conclusions:

Application of the test article to the rabbit's eye can be designated as not irritant.

Executive summary:

Eye irritation potential of FeNaEDDHA was evaluated in an eye irritation study according to the OECD guideline 405. The test material (0.1 mL) was applied into the conjunctival sac of the left eye in 3 New Zealand White rabbits. The animals were checked daily for systemic signs of toxicity and mortality. The reactions were fully reversible within 14 days.

The test material can be considered as not irritating to eyes since the mean scores in treated animals are all below the trigger values defined in the EU CLP (Regulation (EC) No. 1272/2008) for classification as eye irritant.

Reference 2

Endpoint:

eye irritation: in vivo

Type of information:

experimental study

Adequacy of study:

supporting study

Study period:

1993-09-29 to 1993-11-09

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

guideline study

Qualifier:

according to guideline

Guideline:

OECD Guideline 405 (Acute Eye Irritation / Corrosion)

Version / remarks:

1987

Deviations:

no

Qualifier:

according to guideline

Guideline:

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

Version / remarks:

1992

Deviations:

no

GLP compliance:

yes

Species:

rabbit

Strain:

New Zealand White

Details on test animals or tissues and environmental conditions:

TEST ANIMALS
- Source: Dr. K. Thomae GmbH, Chemisch-pharmazeutische Fabrik, D-7950 Biberach/Riss
- Weight at study initiation: 2410 to 2570 g
- Housing: individually in metal cages
- Diet (e.g. ad libitum): ad libitum, standard rabbit pellet-Nafag No.814
- Water (e.g. ad libitum): ad libitum, fresh water
- Acclimation period: at least 5 days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 20 +/- 3 degree C
- Humidity (%): 30 - 70 %
- Photoperiod (hrs dark / hrs light): 12 hours light cycle

Vehicle:

unchanged (no vehicle)

Controls:

other: the right eye remained untreated and sevred as a control

Amount / concentration applied:

TEST MATERIAL
- Amount(s) applied): 80 mg (quantity corresponding to a volume of 0.1 mL)

Duration of treatment / exposure:

Single treatment

Observation period (in vivo):

1, 24, 48, 72 hours; to reveal a possible reversibility, readings were continued on Day 7.

Number of animals or in vitro replicates:

3 (female)

Details on study design:

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

SCORING SYSTEM: documented in the OECD guideline 405

TOOL USED TO ASSESS SCORE: hand-slit lamp

Irritation parameter:

cornea opacity score

Basis:

animal #1

Time point:

other: 24, 48, 72 hrs

Score:

0

Max. score:

4

Irritation parameter:

cornea opacity score

Basis:

animal #2

Time point:

other: 24, 48, 72 hrs

Score:

0

Max. score:

4

Irritation parameter:

cornea opacity score

Basis:

animal #3

Time point:

other: 24, 48, 72 hrs

Score:

0.33

Max. score:

4

Reversibility:

fully reversible

Remarks on result:

other: on day 7

Irritation parameter:

iris score

Basis:

animal #1

Time point:

other: 24, 48, 72 hrs

Score:

0

Max. score:

2

Irritation parameter:

iris score

Basis:

animal #2

Time point:

other: 24, 48, 72 hrs

Score:

0.33

Max. score:

2

Reversibility:

fully reversible

Remarks on result:

other: on day 7

Irritation parameter:

iris score

Basis:

animal #3

Time point:

other: 24, 48, 72 hrs

Score:

0.33

Max. score:

2

Reversibility:

fully reversible

Remarks on result:

other: on day 7

Irritation parameter:

conjunctivae score

Remarks:

redness

Basis:

animal #1

Time point:

other: 24, 48, 72 hrs

Score:

1

Max. score:

3

Reversibility:

fully reversible

Remarks on result:

other: on day 7

Irritation parameter:

conjunctivae score

Remarks:

redness

Basis:

animal #2

Time point:

other: 24, 48, 72 hrs

Score:

1.33

Max. score:

3

Reversibility:

fully reversible

Remarks on result:

other: on day 7

Irritation parameter:

conjunctivae score

Remarks:

redness

Basis:

animal #3

Time point:

other: 24, 48, 72 hrs

Score:

1.33

Max. score:

3

Reversibility:

fully reversible

Remarks on result:

other: on day 7

Irritation parameter:

chemosis score

Basis:

animal #1

Time point:

other: 24, 48, 72 hrs

Score:

0

Max. score:

4

Irritation parameter:

chemosis score

Basis:

animal #2

Time point:

other: 24, 48, 72 hrs

Score:

0.33

Max. score:

4

Reversibility:

fully reversible

Remarks on result:

other: on day 7

Irritation parameter:

chemosis score

Basis:

animal #3

Time point:

other: 24, 48, 72 hrs

Score:

0.33

Max. score:

4

Reversibility:

fully reversible

Remarks on result:

other: on day 7

Irritant / corrosive response data:

Because reactions were observed within 72 hours after instillation of the test article, the observation period was extended to 7 days to determine the reversebility of the eye reactions.

Other effects:

No other effects. The animals gained in bodyweight.

Individual eye scores
	CORNEA	IRIS	CONJUNCTIVA
			redness	chemosis
animal No. 772/F	ce/te	ce/te	ce/te	ce/te
after 1 hr.	0/1	0/0	0/1	0/1
after24 hrs.	0/0	0/0	0/2	0/0
after48 hrs.	0/0	0/0	0/1	0/0
after 72 hrs.	0/0	0/0	0/0	0/0
mean 24-72 hrs.	0/0	0/0	0/1	0/0
after 7 days	0/0	0/0	0/0	0/0
	CORNEA	IRIS	CONJUNCTIVA
			redness	chemosis
animal No. 084/F	ce/te	ce/te	ce/te	ce/te
after 1 hr.	0/1	0/1	0/1	0/1
after 24 hrs.	0/0	0/1	0/2	0/1
after 48 hrs.	0/0	0/0	0/1	0/0
after 72 hrs.	0/0	0/0	0/1	0/0
mean 24-72 hrs.	0/0	0/0.33	0/1.33	0/0.33
after 7 days	0/0	0/0	0/0	0/0
	CORNEA	IRIS	CONJUNCTIVA
			redness	chemosis
animal No. 108/F	ce/te	ce/te	ce/te	ce/te
after 1 hr.	0/1	0/1	0/1	0/1
after 24 hrs.	0/1	0/1	0/2	0/1
after 48 hrs.	0/0	0/0	0/1	0/0
after 72 hrs.	0/0	0/0	0/1	0/0
mean 24-72 hrs.	0/0.33	0/0.33	0/1.33	0/0.33
after 7 days	0/0	0/0	0/0	0/0

ce = control eye

te = test eye

F = female

Interpretation of results:

not irritating

Remarks:

Migrated information Criteria used for interpretation of results: OECD GHS

Conclusions:

Application of the FeNaEDDHA to the rabbit eye can be designated as not irritating.

Executive summary:

An acute eye irritation/corrosion study in albino rabbits was performed to determine the irritant or corrosive potency of FeNaEDDHA in the albino rabbit eye and the associated mucous membranes. The test was based on the OECD Guideline No. 405 (Acute Eye Irritation/ Corrosion) and the EU method B.5 (Acute Toxicity: Eye Irritation/ Corrosion) and was performed on 3 female rabbits, checked for normal eye conditons. 0.1 mL (80 mg) of the test item was placed into the conjunctival sac of the left eye of each animal. The lids were then held together for about one second in order to prevent loss of the test article. The animals were checked daily for systemic symptoms and mortality. Because reactions were observed within 72 hours after instillation of the test article, the observation period was extended to 7 days to determine the reversibility of the eye reactions. According to the GHS Regulation (EC) No. 1272/2008 the test article FeNaEDDHA can be classified as non-irritant to albino rabbit's eye. The eye reactions observed were reversible until the end of the observation period on day 7.

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed (not irritating)

Respiratory irritation

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed (not irritating)

Additional information

Skin irritation

Two acute skin irritation/corrosion studies in albino rabbits to determine whether irritant or corrosive potency exists for the structural analogue test substance Fe(Na)EDDHA (CAS 84539-55-9) (CIBA-GEIGY, 1993c, Report No. 931143; Mercier, 1992, Report No. 209306). These tests were based on the OECD Guideline 404 (Acute Dermal Irritation/Corrosion) and were performed on 3 rabbits, checked for normal skin conditions. A gauze patch bearing 0.5 g of the test article was applied to the right flank of each animal and held in place for 4 hours by an adhesive tape. The studies showed that Fe(Na)EDDHA does not cause skin irritation, as the mean values of the recordings 24 to 72 hours after application were scored 0 in the study performed by CIBA-GEIGY (1993) and the scores determined in the study of Mercier (1992) were all below the trigger values for classification as skin irritant.

Eye irritation

Two eye irritation studies were performed according to OECD Guideline 405 (Acute Eye Irritation/Corrosion) with the read-across test item Fe(Na)EDDHA (CAS 84539-55-9) (CIBA-GEIGY, 1993d; Report No. 931144; Mercier, 1992, Report No. 209305). The tests were performed on 3 New Zealand White rabbits. A volume of 0.1 mL of the test item was placed into the conjunctival sac of the left eye of each animal. The lids were then held together for about one second in order to prevent loss of the test article. The animals were checked daily for systemic symptoms and mortality. The studies showed that the test substance does not cause eye irritation as none of the animals achieved a mean score leading to classification according to GHS (>= 1 for cornea and iris; >= 2 for redness and chemosis).

Justification for classification or non-classification

Skin irritation

According to the classification criteria outlined in the section 3.2.2.2. (Guidance on the Application of CLP criteria, 2013), if the mean value of ≥ 2.3 ≤ 4.0 was reached for erythema/eschar or for oedema in at least 2 of 3 tested animals from gradings at 24, 48 and 72 hours after patch removal, the classification as Skin Irritant would be assigned. The mean values for erythema and oedema measured in the in vivo study of Mercier (1992) are all under the cut-off values triggering C&L. The mean value for erythema/eschar from gradings at 24 -h, 48 -h and 72 -h after patch removal was 1.33 in each animal. The mean values of 0.0, 0.33 and 0.33 for oedema were measured at the same reading points in animal 1, 2 and 3, respectively. In the CIBA-GEIGY (1993) study, the score of 0.0 was measured in all animals at all reading time points. Based on this data, the target substance o,o-Fe(Na)EDDHA does not meet criteria under EU CLP Regulation (EC) No. 1272/2008) for classification and labelling as a skin irritant.

Eye irritation

According to the classification criteria outlined in the section 3.3.2.2. (Guidance on the Application of CLP criteria, 2013), if a substance cause positive but reversible reactions such as corneal opacity (score ≥ 1), iritis (score ≥ 1), conjunctival redness (score ≥ 2) or conjunctival oedema (chemosis) (score ≥ 2) in at least 2 of 3 tested animals from gradings at 24, 48 and 72 hours after application, the classification as Eye Irritant (Category 2) is assigned. The average irritation scores over 24, 48, and 72 hours for corneal opacity were 0.67, 0.0 and 0.0 in animal 1, 2 and 3, respectively. Iritis mean scores of 1.0, 0.33 and 0.33 were yielded for animal 1, 2 and 3, respectively. The conjunctivae mean scores for redness and chemosis were 0.33 in each animal (Mercier, 1992). In another study (CIBA_GEIGY, 1993), the mean scores for the same reading points for corneal opacity were 0.0, 0.0 and 0.33 in animal 1, 2 and 3, respectively. Iritis mean scores of 0.0, 0.33 and 0.33 were yielded for animal 1, 2 and 3, respectively. The conjunctivae mean scores for redness were 1.0, 1.33 and 1.33 in animal 1, 2 and 3, respectively. The chemosis mean scores were 0.0, 0.33 and 0.33 in animal 1, 2 and 3, respectively.

According to these values, no positive reponders were in both eye irritation studies. Therefore, according to Regulation (EC) No. 1272/2008, the target substance o,o-Fe(Na)EDDHA does not need to be classified and labelled as eye irritant.