Reaction mass of Trisodium tris(D-gluconato(2-)-κO1,κO2)ferrate(3-) and Sodium chloride

Endpoint summary

Key value for chemical safety assessment

Skin irritation / corrosion

Link to relevant study records

Reference

Reference 1

Endpoint:

skin irritation: in vitro / ex vivo

Type of information:

experimental study

Adequacy of study:

key study

Study period:

25-31 July 2017

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

other: The study has been performed according to OECD and/or EC guidelines and according to GLP principles.

Qualifier:

according to guideline

Guideline:

other: EU method B.46 (In Vitro Skin Irritation: Reconstructed Human Epidermis Model Test)

Deviations:

no

Qualifier:

according to guideline

Guideline:

other: OECD Guideline no. 439: In Vitro Skin Irritation: Reconstructed Human Epidermis Test Method

Deviations:

no

GLP compliance:

yes (incl. QA statement)

Specific details on test material used for the study:

Yellow powder
Purity: 76.4%
Batch no.: FC-C 11988
Expiry date: 1 November 2017

Test system:

human skin model

Vehicle:

unchanged (no vehicle)

Details on test system:

TEST SITE
- Area of exposure: human epidermis model
- % coverage: 0.38 cm2

REMOVAL OF TEST SUBSTANCE
- Washing (if done): phosphate buffered saline
- Time after start of exposure: 15 minutes

POST INCUBATION PERIOD
- 42 hours

SCORING SYSTEM:
- After a 42 hour incubation period, determination of the cytotoxic (irritancy) effect was performed. Cytotoxicity is expressed as the reduction of mitochondrial dehydrogenase activity measured by formazan production from MTT at the end of the treatment. Cell viability was calculated for each tissue as a percentage of the mean of the negative control tissues.

Control samples:

yes, concurrent negative control

yes, concurrent positive control

Amount/concentration applied:

The test was performed on a total of 3 tissues per test item together with negative and positive controls. The skin was moistened with 5 µl Milli-Q water (Millipore Corp., Bedford, Mass., USA) to ensure close contact of the test item to the tissue and the solid test item (15.18 to 20.30 mg) was added into 12-well plates on top of the skin tissues. Three tissues were treated with 25 µl PBS (negative control) and 3 tissues with 25 µl 5% SDS (positive control) respectively. The positive control was re-spread after 7 minutes contact time.

Duration of treatment / exposure:

Exposure:15 minutes
Post incubation period: 42 hours

Number of replicates:

3

Irritation / corrosion parameter:

other: other: percentage viability

Value:

116

Negative controls validity:

valid

Positive controls validity:

valid

Remarks on result:

other:

Remarks:

Basis: other: percentage of control. Time point: 15 minutes. (migrated information)

The relative mean tissue viability obtained after 15 ± 0.5 minutes treatment with Iron trigluconic acid, trisodium salt compared to the negative control tissues was 116%. Since the mean relative tissue viability for Iron trigluconic acid, trisodium salt was above 50%, Iron trigluconic acid, trisodium salt is considered to be non-irritant.

The positive control had a mean cell viability after 15 ± 0.5 minutes exposure of 5.7%. The absolute mean OD₅₇₀of the negative control tissues was within the laboratory historical control data range. The standard deviation value of the percentage viability of three tissues treated identically was ≤ 18%, indicating that the test system functioned properly.

Interpretation of results:

other: non-irritant

Remarks:

Migrated information

Conclusions:

It is concluded that the test substance is non-irritant in the in vitro skin irritation test.

Executive summary:

The objective of this study was to evaluate Iron trigluconic acid, trisodium salt for its ability to induce skin irritation on a human three dimensional epidermal model (EPISKIN Small model (EPISKIN-SM^TM)). The possible skin irritation potential of Iron trigluconic acid, trisodium salt was tested through topical application for 15 minutes.

The study procedures described in this report were based on the most recent OECD and EC guidelines.

Batch FC-C 11988 of the test item was a yellow powder. Skin tissue was moistened with 5 µl of Milli-Q water and at least 10 mg of the test item was applied directly on top of the skin tissue for 15 ± 0.5 minutes. After a 42 hour post-incubation period, determination of the cytotoxic (irritancy) effect was performed. Cytotoxicity is expressed as the reduction of mitochondrial dehydrogenase activity measured by formazan production from MTT at the end of the treatment.

Skin irritation is expressed as the remaining cell viability after exposure to the test item. The relative mean tissue viability obtained after 15 ± 0.5 minutes treatment with Iron trigluconic acid, trisodium salt compared to the negative control tissues was 116%. Since the mean relative tissue viability for Iron trigluconic acid, trisodium salt was above 50% after 15 ± 0.5 minutes treatment, Iron trigluconic acid, trisodium salt is considered to be non-irritant.

The positive control had a mean cell viability of 5.7% after 15 ± 0.5 minutes exposure. The absolute mean OD₅₇₀(optical density at 570 nm) of the negative control tissues was within the laboratory historical control data range. The standard deviation value of the percentage viability of three tissues treated identically was ≤ 18%, indicating that the test system functioned properly.

In conclusion, Iron trigluconic acid, trisodium salt is non-irritant in the in vitro skin irritation test under the experimental conditions described in this report andshould not be classified according to the Globally Harmonized System of Classification and Labeling of Chemicals (GHS) of the United Nations.

Reference 2

Endpoint:

skin irritation: in vivo

Type of information:

read-across from supporting substance (structural analogue or surrogate)

Adequacy of study:

key study

Study period:

July 2007

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

other: Well conducted study according to GLP

Justification for type of information:

REPORTING FORMAT FOR THE ANALOGUE APPROACH
See section 13

Reason / purpose for cross-reference:

read-across source

Qualifier:

according to guideline

Guideline:

OECD Guideline 404 (Acute Dermal Irritation / Corrosion)

Deviations:

no

Qualifier:

according to guideline

Guideline:

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

Deviations:

no

GLP compliance:

yes (incl. QA statement)

Species:

rabbit

Strain:

Himalayan

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Source: LPT, 24601 Löhndorf, germany
- Age at study initiation: 3-5 months
- Weight at study initiation: 1.8 - 2.3 kg
- Housing: individually
- Diet (e.g. ad libitum): ad libitum
- Water (e.g. ad libitum):ad libitum
- Acclimation period: 20 days


ENVIRONMENTAL CONDITIONS
- Temperature (°C): 20+/- 3°C
- Humidity (%): 30-70%
- Air changes (per hr): 60 per hour
- Photoperiod (hrs dark / hrs light):12/12


IN-LIFE DATES: From: 2. To: 6.July 2007

Type of coverage:

semiocclusive

Preparation of test site:

shaved

Vehicle:

water

Controls:

not required

Amount / concentration applied:

TEST MATERIAL
- Amount(s) applied (volume or weight with unit): 500 mg/animal

Duration of treatment / exposure:

4 h

Observation period:

72 h

Number of animals:

3

Details on study design:

TEST SITE
- Area of exposure: 6 cm²
- % coverage:
- Type of wrap if used: gauze patch


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

Irritation parameter:

erythema score

Basis:

animal: one animal

Time point:

other: 1 hour

Score:

1

Reversibility:

fully reversible

Irritant / corrosive response data:

Very slight erythema (grade 1) was observed in one animal at 1 h after removal of the patch. There were no further skin reactions and no systemic adverse effects.

Interpretation of results:

GHS criteria not met

Remarks:

Migrated information Criteria used for interpretation of results: OECD GHS

Conclusions:

The test iterm is not irritating to the skin.

Executive summary:

In a skin irritation study according to OECD guideline 404 a dose of 500 mg FeNaEDTA was applied to the shaved skin of three male rabbits for 4 hours. Very slight erythema was noted for one animal at 1 hour after patch removal. No other skin effects or systemic effects were noted during the observation period of 72h.

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed (not irritating)

Eye irritation

Link to relevant study records

Reference

Reference 1

Endpoint:

eye irritation: in vitro / ex vivo

Type of information:

experimental study

Adequacy of study:

key study

Study period:

10 May - 14 June 2017

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

guideline study

Qualifier:

according to guideline

Guideline:

OECD Guideline 438 (Isolated Chicken Eye Test Method for Identifying i) Chemicals Inducing Serious Eye Damage and ii) Chemicals Not Requiring Classification for Eye Irritation or Serious Eye Damage)

Deviations:

no

GLP compliance:

yes (incl. QA statement)

Specific details on test material used for the study:

Yellow powder
Purity: 76.4%
Batch no: FC-C 11988
Expiry date: 1 November 2017

Species:

other: chicken eye (slaughter house)

Strain:

other: ROSS, spring chickens

Vehicle:

unchanged (no vehicle)

Amount / concentration applied:

30 mg

Duration of treatment / exposure:

10 seconds

Duration of post- treatment incubation (in vitro):

240 min

Number of animals or in vitro replicates:

3

Details on study design:

Within 2 hours after kill, eyes were carefully dissected and placed in a superfusion apparatus using the following procedure: First the eye-lids were carefully removed without damaging the cornea and a small drop of Fluorescein sodium 2.0% w/v (Minims, Chauvin, England) was applied to the corneal surface for a few seconds and subsequently rinsed off with isotonic saline at ambient temperature. Next, the head with the fluorescein-treated cornea was examined with a slit-lamp microscope (Slit-lamp 900 BP, Haag-Streit AG, Liebefeld-Bern, Switzerland) to ensure that the cornea was not damaged. If undamaged (e.g., fluorescein retention and corneal opacity scores of ≤ 0.5), the eye was further dissected from the head without damaging the eye or cornea. Care was taken to remove the eye-ball from the orbit without cutting off the optical nerve too short.
The enucleated eye was placed in a stainless steel clamp with the cornea positioned vertically and transferred to a chamber of the superfusion apparatus. The clamp holding the eye was positioned in such a way that the entire cornea was supplied with isotonic saline from a bent, stainless steel tube, at a target rate of 0.10-0.15 mL/min (peristaltic pump set at speed 5.00, Watson-Marlow 205CA, Rotterdam, the Netherlands). The chambers of the superfusion apparatus as well as the saline were temperature controlled at approximately 32oC (water pump set at 36.4oC; Lauda 103, Germany).
After placing in the superfusion apparatus, the eyes were examined again with the slit-lamp microscope to ensure that they were not damaged. Corneal thickness was measured using the Depth Measuring Attachment No. I for the Haag-Streit slit-lamp microscope, set at 0.095 mm.
Corneal thickness was expressed in instrument units. An accurate measurement was taken at the corneal apex of each eye.
Eyes with a corneal thickness deviating more than 10% of the average corneal thickness of the eyes, eyes showing opacity (score higher than 0.5), or were unacceptably stained with fluores-cein (score higher than 0.5) indicating the cornea to be permeable, or eyes that showed any other signs of damage, were rejected as test eyes and replaced.
Each eye provided its own baseline values for corneal swelling, corneal opacity and fluorescein retention. For that purpose, after an equilibration period of 45-60 minutes, the corneal thickness of the eyes was measured again to determine the zero reference value for corneal swelling calculations.
At time t = 0 (i.e. immediately after the zero reference measurement), the following procedure was applied for each test eye: The clamp holding the test eye was placed on paper tissues outside the chamber with the cornea facing upwards.
Next, the eyes (corneas) were treated with the study substance according to the following scheme:
negative control - saline - 30 uL - 10 sec - 20 ml saline for rinsing (one eye)
positive control - NaOH - 30 mg - 10 sec - 20 ml saline for rinsing (3 eyes)
test substance - 30 mg - - 10 sec - 20 ml saline for rinsing (3 eyes)
After rinsing, each eye in the holder was returned to its chamber.
The eyes were examined at approximately 0, 30, 75, 120, 180 and 240 minutes after treatment, using the criteria and scoring system given in the attachment. Fluorescein retention was only scored at approximately 30 minutes after treatment. All examinations were carried out with the slit-lamp microscope.
After the final examination, the test substance treated eyes, the negative and positive control eyes were preserved in a neutral aqueous phosphate-buffered 4% solution of formaldehyde. The corneas were embedded in paraffin wax, sectioned at ca 4 μm and stained with PAS (Periodic Acid-Schiff). The microscopic slides were subjected to histopathological examination.

Irritation parameter:

cornea opacity score

Value:

1

Vehicle controls validity:

not applicable

Negative controls validity:

valid

Positive controls validity:

valid

Remarks on result:

positive indication of irritation

Irritation parameter:

fluorescein retention score

Value:

2

Vehicle controls validity:

not applicable

Negative controls validity:

valid

Positive controls validity:

valid

Remarks on result:

positive indication of irritation

Irritation parameter:

other: Swelling

Value:

1

Vehicle controls validity:

not applicable

Negative controls validity:

valid

Positive controls validity:

valid

Remarks on result:

no indication of irritation

Other effects / acceptance of results:

Microscopic examination of the cornea treated with the negative control (saline) did not reveal any abnormalities. Microscopic examination of the corneas treated with the positive control NaOH revealed severe erosion (3/3 corneas), severe necrosis (1/3 corneas) of the epithelium, disorder of stromal fibres (3/3 corneas) and endothelial necrosis (3/3 corneas). Microscopic examination of the corneas treated with Iron trigluconic acid, trisodium salt revealed very slight erosion of the epithelium in all three corneas.

Interpretation of results:

other: irritating in vitro

Conclusions:

Iron trigluconic acid, trisodium salt caused corneal effects consisting of no or very slight corneal swelling (mean of 1%), slight opacity (mean score of 1.0) and moderate fluorescein retention (mean score of 2.0). Therefore, an in vivo study was also performed.

Executive summary:

Iron trigluconic acid, trisodium salt was evaluated neat for eye irritation potential in the Isolated Chicken Eye (ICE) test. In addition, the test included a negative control (saline) and a positive control (NaOH). Chicken eyes were obtained from slaughter animals used for human consumption. The isolated chicken eyes were exposed to a single application of 30 mg of the test substance for 10 seconds followed by a 20 mL saline rinse. Three main parameters were measured to disclose possible adverse eye effects: corneal thickness (expressed as corneal swelling), corneal opacity and fluorescein retention of damaged epithelial cells. In addition, histopathology of the corneas was performed.

Iron trigluconic acid, trisodium salt caused corneal effects which could lead to a Category 2/2B classification, consisting of no or very slight corneal swelling (mean of 1%), slight opacity (mean score of 1.0) and moderate fluorescein retention (mean score of 2.0). Microscopic examination of the corneas revealed very slight erosion of the epithelium in all three corneas.

The negative control eye did not show any corneal effect and demonstrated that the general conditions during the tests were adequate. Microscopic examination of the cornea did not reveal any abnormalities. The positive control NaOH caused severe corneal effects and demonstrated the ICE test valid to detect severe eye irritants. Microscopic examination of the corneas revealed severe erosion (3/3 corneas), severe necrosis (1/3 corneas) of the epithelium, disorder of stromal fibres (3/3 corneas) and endothelial necrosis (3/3 corneas).

Applying the classification criteria of the ICE, the following irritation classifications can be assigned:

- Category 2B:“Mild irritant/causes eye irritation” (UN-GHS classification);

- Category 2:“Irritating to eyes” (EU-CLP classification).

Reference 2

Endpoint:

eye irritation: in vivo

Type of information:

experimental study

Adequacy of study:

key study

Study period:

19 October 2017 - 03 November 2017

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

guideline study

Justification for type of information:

The test method and number of animals were based on the test guidelines.
This type of study plan was reviewed and agreed by the Laboratory Animal Welfare Officer and the Ethical Committee of Charles River Den Bosch as required by the Dutch Act on Animal Experimentation (February 1997).

Qualifier:

according to guideline

Guideline:

OECD Guideline 405 (Acute Eye Irritation / Corrosion)

Version / remarks:

2012

Deviations:

no

Qualifier:

according to guideline

Guideline:

EPA OPPTS 870.2400 (Acute Eye Irritation)

Version / remarks:

August 1998

Deviations:

no

Qualifier:

according to guideline

Guideline:

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

Version / remarks:

May 2008

Deviations:

no

Qualifier:

according to guideline

Guideline:

other: Appendix to Director General Notification, No. 12-Nousan-8147. Agricultural Production Bureau, Ministry of Agriculture, Forestry and Fisheries of Japan (JMAFF)

Version / remarks:

November 2000, including the most recent revisions.

Deviations:

no

GLP compliance:

yes

Specific details on test material used for the study:

pH: 9.5 (concentration of 1% in aqueous solution)

Species:

rabbit

Strain:

New Zealand White

Details on test animals or tissues and environmental conditions:

TEST ANIMALS
- Source: Charles River France, L’Arbresle, France
- Age at study initiation: 12-13 weeks old
- Weight at study initiation: 2574 - 2990 g
- Housing: individually, in cages with perforated floors
- Diet: Pelleted diet for rabbits (Global Diet 2030 Teklad®, Mucedola, Milanese, Italy), once daily throughout the study period.
- Water: municipal tap-water, ad libitum
- Acclimation period: at least 5 days

ENVIRONMENTAL CONDITIONS (set to maintain)
- Temperature (°C): 18-24 (actual: 19.6-19.7)
- Humidity (%): 40-70 (actual: 72-75)
- Air changes (per hr): >= 10
- Photoperiod (hrs dark / hrs light): 12/12

IN-LIFE DATES: From: 23 October 2017 To: 03 November 2017

Vehicle:

unchanged (no vehicle)

Controls:

yes, concurrent no treatment

Amount / concentration applied:

TEST MATERIAL
- Amount applied: 53.6 mg (range 53.4 – 53.8 mg)

Duration of treatment / exposure:

Single treatment followed by observations at 1, 24, 48 and 72 hours and/or 14 days after instillation

Observation period (in vivo):

14 days

Number of animals or in vitro replicates:

3 males in a stepwise manner: starting with one animal and followed by treatment of two additional animals 4 days later.

Details on study design:

PAIN MANAGEMENT: One hour prior to instillation of the test item, buprenorphine (Buprenodale®) 0.01 mg/kg was administered by subcutaneous injection and five minutes prior to instillation of the test item, two drops of the topical anaesthetic 0.5% proparacaine hydrochloric ophthalmic solution (Alcaine eye drops®) were applied to both eyes.

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

SCORING SYSTEM: according to Draize

TOOL USED TO ASSESS SCORE: 2% fluorescein in water (pH adjusted to 7.0)

Irritation parameter:

cornea opacity score

Basis:

animal #1

Time point:

24/48/72 h

Score:

0

Max. score:

4

Irritation parameter:

cornea opacity score

Basis:

animal #2

Time point:

24/48/72 h

Score:

0

Max. score:

4

Irritation parameter:

cornea opacity score

Basis:

animal #3

Time point:

24/48/72 h

Score:

0

Max. score:

4

Irritation parameter:

iris score

Basis:

animal #1

Time point:

24/48/72 h

Score:

0

Max. score:

2

Irritation parameter:

iris score

Basis:

animal #2

Time point:

24/48/72 h

Score:

0

Max. score:

2

Irritation parameter:

iris score

Basis:

animal #3

Time point:

24/48/72 h

Score:

0

Max. score:

2

Irritation parameter:

conjunctivae score

Remarks:

(redness)

Basis:

animal #1

Time point:

24/48/72 h

Score:

1.3

Max. score:

3

Reversibility:

fully reversible within: 7 days

Irritation parameter:

conjunctivae score

Remarks:

(redness)

Basis:

animal #2

Time point:

24/48/72 h

Score:

1.3

Max. score:

3

Reversibility:

fully reversible within: 7 days

Irritation parameter:

conjunctivae score

Remarks:

(redness)

Basis:

animal #3

Time point:

24/48/72 h

Score:

1.3

Max. score:

3

Reversibility:

fully reversible within: 7 days

Irritation parameter:

chemosis score

Basis:

animal #1

Time point:

24/48/72 h

Score:

1.3

Max. score:

4

Reversibility:

fully reversible within: 7 days

Irritation parameter:

chemosis score

Basis:

animal #2

Time point:

24/48/72 h

Score:

1.3

Max. score:

4

Reversibility:

fully reversible within: 7 days

Irritation parameter:

chemosis score

Basis:

animal #3

Time point:

24/48/72 h

Score:

1.3

Max. score:

4

Reversibility:

fully reversible within: 7 days

Irritant / corrosive response data:

- Irritation and corrosion: Irritation consisted of redness, chemosis and discharge and was completely reversed within 7 days in all animals.
Neither iridial irritation or corneal opacity nor corneal epithelial damage was observed.
- Coloration/remnants: No staining of (peri) ocular tissues by the test item was observed and no test item remnants were seen.
- Toxicity/mortality: No signs of systemic toxicity were observed in the animals during the test period and no mortality occurred.

Interpretation of results:

GHS criteria not met

Conclusions:

Based on the results of an in vivo eye irritation study performed according to OECD 405 and GLP principles, Iron trigluconic acid, trisodium salt is not classified for irritation according to GHS and Regulation (EC) No. 1272/2008.

Reference 3

Endpoint:

eye irritation: in vivo

Type of information:

read-across from supporting substance (structural analogue or surrogate)

Adequacy of study:

supporting study

Study period:

July 2007

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

other: Well conducted study according to GLP

Justification for type of information:

REPORTING FORMAT FOR THE ANALOGUE APPROACH
See section 13

Reason / purpose for cross-reference:

read-across source

Qualifier:

according to guideline

Guideline:

OECD Guideline 405 (Acute Eye Irritation / Corrosion)

Deviations:

no

Qualifier:

according to guideline

Guideline:

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

Deviations:

no

GLP compliance:

yes (incl. QA statement)

Species:

rabbit

Strain:

Himalayan

Details on test animals or tissues and environmental conditions:

TEST ANIMALS
- Source: LPT germany
- Age at study initiation: 4-5 months
- Weight at study initiation: 2.2-2.4
- Housing: individually
- Diet (e.g. ad libitum): ad libitum
- Water (e.g. ad libitum):ad libitum
- Acclimation period: 20 days


ENVIRONMENTAL CONDITIONS
- Temperature (°C): 20 +/-3°C
- Humidity (%): 30-70%
- Air changes (per hr): 60
- Photoperiod (hrs dark / hrs light): 12/12


IN-LIFE DATES: From: 4. To: 12.July 2007

Vehicle:

unchanged (no vehicle)

Irritation parameter:

cornea opacity score

Basis:

animal #3

Time point:

other: 24, 48, 72h, 4,5,6-days

Score:

1

Max. score:

4

Reversibility:

fully reversible within: 7 days

Irritation parameter:

conjunctivae score

Basis:

mean

Time point:

other: 1, 24, 48, 72h, 4 days

Score:

1

Max. score:

3

Reversibility:

fully reversible within: 5 days

Irritant / corrosive response data:

Under the present test conditions a single administration of 100 mg FeNaEDTA per animal into the conjunctival sac of the right eye of three rabbits caused the following effects:
Corneal opacity (grad 1) was observed in animal no. three 24 hours to 6 days after instillation.
The fluorescein test performed 24 hours after instillation revealed corneal staining in animal no. 3 (up to 1/4 of the surface).
Conjunctival redness (grad 1) was observed in animal no. one 60 minutes, in animal no. two 60 minutes to 48 hours and in animal no. three 24 hours to 4 days after instillation.
In addition, secretion was observed in all 3 animals 1 hour after instillation.
The irises were not affected by instillation of the test item.
There were no systemic intolerance reactions.

Time after administration	C O R N E A	I R I S	C O N J U N C T I V A E	C H E M O S I S
	Opacity		Redness
	A n i m a l  n o. : 1 / 2 / 3
before dosing	0/0/0	0/0/0	0/0/0	0/0/0
60 minutes	0/0/0	0/0/0	1/1/0	0/0/0
24 hours	0/0/1	0/0/0	0/1/1	0/0/0
48 hours	0/0/1	0/0/0	0/1/1	0/0/0
72 hours	0/0/1	0/0/0	0/0/1	0/0/0
4 days	-/-/1	-/-/0	-/-/1	-/-/0
5 days	-/-/1	-/-/0	-/-/0	-/-/0
6 days	-/-/1	-/-/0	-/-/0	-/-/0
7 days	-/-/0	-/-/0	-/-/0	-/-/0

Interpretation of results:

GHS criteria not met

Remarks:

Migrated information Criteria used for interpretation of results: OECD GHS

Conclusions:

Although the test item induced slight irritation, no classification is needed according to OECD-GHS.

Executive summary:

An eye irritation study with three male Himalyan rabbits according to OECD guideline 405 and GLP was performed.

A single administration of 100 mg FeNaEDTA per animal into the conjunctival sac of the right eye of three rabbits caused the following effects:

Corneal opacity (grade 1) was observed in animal no. three 24 hours to 6 days after instillation.

The fluorescein test performed 24 hours after instillation revealed corneal staining in animal no. 3 (up to 1/4 of the surface).

Conjunctival redness(grade 1) was observed in animal no. one 60 minutes, in animal no. two 60 minutes to 48 hours and in animal no. three 24 hours to 4 days after instillation. In addition, secretion was observed in all 3 animals 1 hour after instillation.

Irises were not affected by instillation of the test item.

There were no systemic intolerance reactions.

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed (not irritating)

Respiratory irritation

Endpoint conclusion

Endpoint conclusion:

no study available

Justification for classification or non-classification

Based on the available in vitro and in vivo studies with Fe-gluconate and its read across substances there is no need to classify according to GHS.