Potassium [[N,N'-ethylenebis[N-(carboxymethyl)glycinato]](4-)-N,N',O,O',ON,ON']ferrate(1-)

Endpoint summary

Description of key information

The test item is not considered to be irritating to the skin or eyes. A study for respiratory irritation is not available; however, an acute inhalation study (Haferkorn, 2008) with EDTA-FeNa does not give any indication that the test substance EDTA-FeK should be regarded as a respiratory irritant.

Key value for chemical safety assessment

Skin irritation / corrosion

Link to relevant study records

Reference

Endpoint:

skin irritation: in vitro / ex vivo

Type of information:

experimental study

Adequacy of study:

key study

Study period:

17-Jun-2014 to 23-Jun-2014

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)

Amount / concentration applied:

TEST MATERIAL
- Amount(s) applied (volume or weight with unit): 11.5 to 12.6 mg, moistened with 5 µl water
(EDTA-FeK could not be spread to match the size of the tissue due to the hygroscopic properties.)

NEGATIVE CONTOL:
- Amount(s) applied (volume or weight with unit): 25 µl Phosphate buffered saline

POSITIVE CONTROL
- Amount(s) applied (volume or weight with unit): 25 µl
- Concentration (if solution): 5% (aq) Sodium dodecyl sulphate

Duration of treatment / exposure:

Exposure:15 minutes
Post incubation period: 42 hours

Details on study design:

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.
In addition to the normal procedure, three killed tissues treated with test substance and three killed non treated tissues were used for the cytotoxicity evaluation with MTT.

Irritation / corrosion parameter:

other: other: percentage viability

Value:

87

Remarks on result:

other:

Remarks:

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

Interpretation of results:

not irritating

Remarks:

Migrated information Criteria used for interpretation of results: EU

Conclusions:

EDTA-FeK is non-irritant in the in vitro skin irritation test.

Executive summary:

Skin irritation is expressed as the remaining cell viability after exposure to the test substance. The relative mean tissue viability obtained after 15 minutes treatment with EDTA-FeK compared to the negative control tissues was 87%. Since the mean relative tissue viability for EDTA-FeK was above 50% after 15 minutes treatment EDTA-FeK is considered to be non-irritant.

 

The positive control had a mean cell viability of 35% after 15 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.

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed (not irritating)

Eye irritation

Link to relevant study records

Reference

Endpoint:

eye irritation: in vitro / ex vivo

Type of information:

experimental study

Adequacy of study:

key study

Study period:

19-May-2014 to 20-May-2014

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: OECD guideline 437 “Bovine Corneal Opacity and Permeability 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

Qualifier:

according to guideline

Guideline:

other: EU Method B.47 “Bovine corneal opacity and permeability method for identifying ocular corrosives and severe irritants

Deviations:

no

GLP compliance:

yes

Amount / concentration applied:

TEST MATERIAL
- Amount(s) applied (volume or weight with unit): approx. 750 µl 20% (w/w) solution per cornea

NEGATIVE CONTROL
- Amount(s) applied (volume or weight with unit): 750 µl of physiological saline per cornea

POSITIVE CONTROL
Amount(s) applied (volume or weight with unit): 750 µl per cornea
Concentration (if solution): 20% (w/v) Imidazole

Duration of treatment / exposure:

240 minutes

Details on study design:

TEST SITE
- Isolated bovine cornea

REMOVAL OF TEST SUBSTANCE
- Washing (if done): yes
- Time after start of exposure: 240 minutes

SCORING SYSTEM:
- After exposure the cornea is thoroughly rinsed to remove the test substance followed by immediate opacity measurement and permeability evaluation of the cornea.

- The mean opacity and mean permeability values (OD490) were used for each treatment group to calculate an in vitro score:

In vitro irritancy score (IVIS) = mean opacity value + (15 x mean OD490 value).


TOOL USED TO ASSESS SCORE:
- opacitymeter and microplate reader

DATA EVALUATION:
In vitro score range UN GHS
≤ 3 No Category
> 3; ≤ 55 No prediction can be made
>55 Category 1

Irritation parameter:

other: In vitro irritancy score (IVIS)

Basis:

mean

Time point:

other: 240 minutes

Score:

-0.1

Other effects:

A pH effect of the test substance was observed on the rinsing medium, the corneas were rinsed until no colour change of the medium was observed

Interpretation of results:

not irritating

Remarks:

Migrated information Criteria used for interpretation of results: EU

Conclusions:

EDTA-FeK is not irritant or corrosive in the Bovine Corneal Opacity and Permeability test

Executive summary:

The negative control responses of the opacity and permeability values were less than the upper limits of the laboratory historical range indicating that the negative control did not induce irritancy on the corneas.The mean in vitro irritancy score of the positive control (20% (w/v) Imidazole) was 113 and within the historical positive control data range. It was therefore concluded that the test conditions were adequate and that the test system functioned properly.

EDTA-FeK did not induce ocular irritation through both endpoints, resulting in a mean in vitro irritancy score of -0.1 after 240 minutes of treatment.

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed (not irritating)

Respiratory irritation

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed (not irritating)

Additional information

The key studies (recently performed according to current guidelines and GLP) did not result in skin or eye irritation in vitro; studies with EDTA-FeNa showed slight irritation effects but do not require classification.

Justification for selection of skin irritation / corrosion endpoint:

For EDTA-FeK only an in vitro skin irritation study was carried out based on the absence of skin irritation for the read across substance EDTA-FeNa (see also section 13).

Justification for selection of eye irritation endpoint:

For EDTA-FeK only an in vitro eye irritation study was carried out based on the absence of eye irritation for the read across substance EDTA-FeNa (see also section 13)

Justification for classification or non-classification

Key studies with the test substance and the read across substance EDTA-FeNa did not show irritation. Therefore classification for irritation/corrosion is not warranted.