Hydrogen (glycinato-N,O)[sulphato(2-)-O,O']ferrate(1-)

Endpoint summary

Description of key information

- test according to OECD guideline 439 (2019), human kertinocytes, 3 tissues, were exposed to 25 mg ferrous monoglycinate sulfate for 1h. After a postincubation time of 42h the viability was determined using the MTT assay, the mean viability was > 50% (76%), not classified

- test according to OECD guideline 437 (BCOP), 20 % suspension of theferrous monoglycinate sulfate in HBSS induced only a minimal relative increase of the corneal opacity and permeability as compared to negative control. The calculated mean in vitro score was 3.25, which lies in the range of IVIS > 3 and ≤ 55 which does not allow classification.

- QSAR Toolbox prediction, no alerts found for corrosivity to the eye using the 'BfR exclusion rules' profiler

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:

- 2020-10-31

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

guideline study

Qualifier:

according to guideline

Guideline:

OECD Guideline 439 (In Vitro Skin Irritation: Reconstructed Human Epidermis Test Method)

Version / remarks:

adopted 18 June 2019

Deviations:

no

GLP compliance:

yes (incl. QA statement)

Test system:

human skin model

Source species:

human

Cell type:

non-transformed keratinocytes

Cell source:

other: Cell source was not reported

Justification for test system used:

This test method is able to detect chemicals that cause skin irritation, i.e. produce reversible damage to the skin and allows for hazard identification in accordance with UN GHS “Category 2”. Depending on the regulatory framework it can also be used to identify non-classified chemicals.

Vehicle:

other: sterile DBPS

Details on test system:

RECONSTRUCTED HUMAN EPIDERMIS (RHE) TISSUE
- Model used: reconstituted three-dimensional human skin model EpiDerm™ (MatTek)
- Tissue batch number(s):
- Date of initiation of testing:

TEMPERATURE USED FOR TEST SYSTEM
- Temperature used during treatment / exposure: 25 ± min at room temperature and 35 ± 1min at 37°C
- Temperature of post-treatment incubation (if applicable): 37°C for 42 h

REMOVAL OF TEST MATERIAL AND CONTROLS
-Volume and number of washing steps: 15 times with DBPS and subsequently submerged three-times with 150 µL DBPS and shaken to remove rests of the test item
- Observable damage in the tissue due to washing:
- Modifications to validated SOP:

MTT DYE USED TO MEASURE TISSUE VIABILITY AFTER TREATMENT / EXPOSURE
- MTT concentration: 1 mg/mL
- Incubation time: 3h ± 5 min
- Spectrophotometer: plate spectrophotometer
- Wavelength: 570 nm
- Filter bandwidth: with a filter band pass of maximum ± 30 nm without reference wavelength


FUNCTIONAL MODEL CONDITIONS WITH REFERENCE TO HISTORICAL DATA
- Viability:
- Barrier function:
- Morphology:
- Contamination:
- Reproducibility:

NUMBER OF REPLICATE TISSUES: triplicate

CONTROL TISSUES USED IN CASE OF MTT DIRECT INTERFERENCE
- Fresh tissues / killed tissues
- Procedure used to prepare the killed tissues (if applicable):
- N. of replicates :
- Method of calculation used:

NUMBER OF INDEPENDENT TEST SEQUENCES / EXPERIMENTS TO DERIVE FINAL PREDICTION:

PREDICTION MODEL / DECISION CRITERIA (choose relevant statement)
- The test substance is considered to be corrosive /irritant to skin if the viability after 1 hour exposure is less than 50%.
- The test substance is considered to be non-corrosive/irritant to skin if the viability after 1 hour exposure is greater than or equal to 50%.

Control samples:

yes, concurrent no treatment

yes, concurrent positive control

Amount/concentration applied:

TEST MATERIAL
- Amount(s) applied (volume or weight with unit): 25 mg and 25 µL to moistened the tissue

VEHICLE
- Amount(s) applied (volume or weight with unit): 25 µL DBPS
- Lot/batch no. (if required): Cat. No.: 14040-091

NEGATIVE CONTROL
- Amount(s) applied (volume or weight): 30 µL DBPS

POSITIVE CONTROL
- Amount(s) applied (volume or weight): 30 µL SDS solution
- Concentration (if solution): 5%

Duration of treatment / exposure:

1h

Duration of post-treatment incubation (if applicable):

42 h

Number of replicates:

triplicate

Irritation / corrosion parameter:

% tissue viability

Run / experiment:

mean of three treatments with the test material

Value:

76

Vehicle controls validity:

valid

Negative controls validity:

not examined

Positive controls validity:

valid

Remarks on result:

no indication of irritation

Other effects / acceptance of results:

- OTHER EFFECTS:
- Visible damage on test system: Not reported
- Direct-MTT reduction:
- Colour interference with MTT:

DEMONSTRATION OF TECHNICAL PROFICIENCY:

ACCEPTANCE OF RESULTS:
- Acceptance criteria met for negative control: Please refer to the 'any other information on results incl. tables' section
- Acceptance criteria met for positive control: Please refer to the 'any other information on results incl. tables' section
- Acceptance criteria met for variability between replicate measurements: Please refer to the 'any other information on results incl. tables' section
- Range of historical values if different from the ones specified in the test guideline:

Results are draft report results which are reported in more detail on the next update

Interpretation of results:

GHS criteria not met

Conclusions:

In the present in vitro test conducted according to OECD guideline 439, 25 mg ferrous monoglycinate sulfate were applied to human keratinocytes for 1h. Afterwards the cell viability was measured with MTT at 570 nm. The mean measured viability as compared to the negative controls for the test item was 76%, thus the test item is not classified according to Regulation (EU) No. 1272/2008 (CLP) and the Globally Harmonized System for Classification and Labelling of Chemicals (GHS)

Executive summary:

In a dermal irritation study performed in accordance with OECD Guideline 439 (In Vitro Skin Irritation) (adopted 18 June, 2019), ferrous monoglycinate sulfate (100% a.i.) was applied to the three-dimensional human epidermis model tissue for an exposure period of 1 h in triplicates. 25 μL of DBPS were topically applied to the epidermal surface in order to improve further contact between the solid and the epidermis. Each approximately 25 mg of the test item were applied to the wetted tissues. The test item was spread to match the surface of the tissue.

After 25 minutes exposure at room temperature and 35 minutes at 37°C, the tissues were washed with DBPS to remove any residual test material. Subsequently the tissue constructs were incubated for 42 h at 37°C. Cytotoxicity (irritancy) was expressed as the reduction of mitochondrial dehydrogenase activity measured by formazan production from MTT at the end of the treatment.

The positive (5% SDS) and negative (DBPS) control gave responses that were within the acceptance criteria and as such demonstrated the validity of the study.

The relative mean tissue viability obtained after 1h treatment with ferrous monoglycinate sulfate compared to the negative control tissues was 76%. Since the mean relative tissue viability for the test substance was above 50%, ferrous monoglycinate is identified to be not irritating.

Endpoint conclusion

Endpoint conclusion:

adverse effect observed (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:

2019-10-10 to 2019-12-12

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

guideline study

Qualifier:

according to guideline

Guideline:

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)

Version / remarks:

October 2017

Deviations:

no

Qualifier:

according to guideline

Guideline:

EU method B.47 (Bovine corneal opacity and permeability test method for identifying ocular corrosives and severe irritants)

Version / remarks:

February 2017

Deviations:

no

Qualifier:

according to guideline

Guideline:

other: OECD Guideline for the Testing of Chemicals, Series on Testing and Assessment No. 160

Version / remarks:

“GUIDANCE DOCUMENT ON “THE BOVINE CORNEAL OPACITY AND PERMEABILITY (BCOP) AND ISOLATED CHICKEN EYE (ICE) TEST METHODS: COLLECTION OF TISSUES FOR HISTOLOGICAL EVALUATION AND COLLECTION OF DATA ON NON-SEVERE IRRITANTS”; 25. Oct. 2011

GLP compliance:

yes (incl. QA statement)

Species:

cattle

Strain:

not specified

Details on test animals or tissues and environmental conditions:

SOURCE OF COLLECTED EYES
- Source: slaughterhouse Müller Fleisch GmbH, Industriestraße 42, 75217 Birkenfeld, Germany
- Number of animals: not specified
- Characteristics of donor animals (e.g. age, sex, weight): between 12 and 60 months old
- Storage, temperature and transport conditions of ocular tissue (e.g. transport time, transport media and temperature, and other conditions): The eyes were transported to the test facility in Hanks’ Balanced Salt Solution with 1% Penicillin-Streptomycin solution (Penicillin 100 U/mL, Streptomycin 100 µg/mL) in a suitable cooled container within 1 hour and 10 minutes.
- Time interval prior to initiating testing: 1 h
- indication of any existing defects or lesions in ocular tissue samples: only corneas which were free from damages were used
- Indication of any antibiotics used: no

Vehicle:

Hank's balanced salt solution

Controls:

yes, concurrent positive control

yes, concurrent negative control

Amount / concentration applied:

TEST MATERIAL
- Amount(s) applied (volume or weight with unit): 750 µL
- Concentration (if solution): 20 % (w/v)
VEHICLE
- Amount(s) applied (volume or weight with unit): 750 µL

Duration of treatment / exposure:

4 h

Duration of post- treatment incubation (in vitro):

90 min

Number of animals or in vitro replicates:

3 corneas

Details on study design:

SELECTION AND PREPARATION OF CORNEAS: After the arrival of the corneas, they were examined and only corneas which were free from damages were used. The corneas were excised with a scalpel and cut from the globe with a 2-3 mm ring of sclera around the outside. Each cornea was transferred to a cornea holder in which pre-warmed cMEM (32 ± 1 °C) without phenol red was filled. The holders were then incubated for 1 hour in the incubation chamber at 32 ± 1 °C. After the initial incubation, the medium was completely changed and the baseline opacity for each cornea was recorded.
QUALITY CHECK OF THE ISOLATED CORNEAS: None of the corneas showed tissue damage; therefore, all corneas were used.
NUMBER OF REPLICATES: 3
NEGATIVE CONTROL USED: yes, concurrent vehicle
POSITIVE CONTROL USED: yes, Imidazole, 20 % solution in HBSS
APPLICATION DOSE AND EXPOSURE TIME: 750 µL each for 4 h
TREATMENT METHOD: closed chamber for controls. Open chamber for test item suspension.
POST-INCUBATION PERIOD: yes, 90 min
REMOVAL OF TEST SUBSTANCE
- Number of washing steps after exposure period: thorough rinsing
METHODS FOR MEASURED ENDPOINTS:
- Corneal opacity: opacitometer
- Corneal permeability: passage of sodium fluorescein dye measured with the aid of microtiter plate reader (OD492)
SCORING SYSTEM: In Vitro Irritancy Score (IVIS)
DECISION CRITERIA: as indicated in the TG.

Irritation parameter:

in vitro irritation score

Run / experiment:

1-3

Value:

3.25

Vehicle controls validity:

not applicable

Negative controls validity:

valid

Positive controls validity:

valid

Other effects / acceptance of results:

OTHER EFFECTS:
- Visible damage on test system: not reported
ACCEPTANCE OF RESULTS:
- Acceptance criteria met for negative control: yes
- Acceptance criteria met for positive control: yes

Findings and Results

Opacity and Permeability Values

The illuminance (unit: LUX) values which were measured before and after exposure are given in the following table:

Table 1: Illuminance Values. Rep. = Replicate

Parameter	Negative Control			Test Item			Positive Control
	1. Rep.	2. Rep.	3. Rep.	1. Rep.	2. Rep.	3. Rep.	1. Rep.	2. Rep.	3. Rep.
(I) Measured values before exposure	1051	1056	1057	1030	1037	1047	1017	1027	1028
(I) Measured values after exposure	1039	966	1026	915	909	942	350	389	366

The values in the following tables present the calculated opacity values, according to evaluation.

Table 2: Opacity Values Negative Control. Rep. = Replicate

Parameter	Negative Control
	1. Rep.	2. Rep.	3. Rep.
Opacity before exposure	2.10	1.90	1.86
Opacity after exposure	2.58	5.75	3.11
Opacity Difference	0.48	3.85	1.25
Mean Opacity Difference	1.86

Table 3: Opacity Values Test Item and Positive Control. Rep. = Replicate.

Parameter	Test Item			Positive Control
	1. Rep.	2. Rep.	3. Rep.	1. Rep.	2. Rep.	3. Rep.
Opacity before exposure	2.66	2.46	2.30	3.49	3.07	3.03
Opacity after exposure	6.22	6.66	5.61	85.25	72.75	79.80
Opacity Difference	3.57	4.20	3.31	81.76	69.68	76.77
Opacity Difference corrected	1.71	2.34	1.46	79.90	67.82	74.91
Mean Opacity Difference corrected	1.83			74.21

For the permeability measurement, three replicates for each treatment group were measured three times. cMEM without phenol red was measured as blank value as well. The optical density values at 492 nm are given in the following tables:

Table 4: Optical density at 492 nm of Blank.

Parameter	cMEM without phenol red
1. Measurement	0.037
2. Measurement	0.037
3. Measurement	0.034
Mean	0.036

Table 5: Optical density at 492 nm of Negative Control, Test Item and Positive Control. Rep. = Replicate. * Note: Two replicates for the positive control were obtained by measurement of a fivefold diluted solution and multiplication of the absorbances with factor 5.

Parameter	Negative Control			Test Item			Positive Control
	1. Rep.	2. Rep.	3. Rep.	1. Rep.	2. Rep.	3. Rep.	1. Rep.	2. Rep.	3. Rep.
1.Measure-ment	0.052	0.053	0.047	0.040	0.039	0.036	1.771	0.638	0.599
2.Measure-ment	0.052	0.055	0.046	0.041	0.038	0.038	1.746	0.690	0.589
3.Measure-ment	0.052	0.054	0.048	0.040	0.039	0.037	1.769	0.685	0.060
1.Measure-ment – blank	0.0160	0.0170	0.0110	0.0040	0.0030	0.0000	1.7350	0.6020	0.5630
2.Measure-ment – blank	0.0160	0.0190	0.0100	0.0050	0.0020	0.0020	1.7100	0.6540	0.5530
3.Measure-ment – blank	0.0160	0.0180	0.0120	0.0040	0.0030	0.0010	1.7330	0.6490	0.0236
Mean of each replicate	0.0160	0.0180	0.0110	0.0043	0.0027	0.0010	1.7260	0.6350	0.3799
Mean of the 3 replicates	0.0150			--			--
Corrected	--	--	--	-0.0107	-0.0123	-0.0140	1.7110	3.1600*	1.8843*
Corrected mean of the 3 replicates	--			-0.0123			2.2518

IVIS Values

The calculated IVIS for each replicate and the corresponding means are presented in the following table:

Table 6: IVIS

Test Group	IVIS	Mean IVIS	Relative Standard Deviation IVIS
Negative Control HBSS	0.72	2.08	86.23%
	4.12
	1.41
Test Item	3.31	3.25	20.09%
	3.88
	2.58
Positive Control 20% imidazole solution	105.57	107.99	5.91%
	115.22
	103.18

Note: the high relative standard deviations of the IVIS of the negative control and test item are due to mathematical reasons, as the respective means are very small.

Validity

According to the guideline, the test is considered as valid if the positive control causes an IVIS that falls within two standard deviations of the current historical mean.

The mean IVIS of the negative control has to show an IVIS ≤ 3.

The validity criteria and findings are given in the following table:

Table 7: Validity

Parameter	Criterion	Found	Assessment
Mean IVIS of negative control HBSS	≤ 3	2.08	ok
Mean IVIS of positive control 20% imidazole solution	75.63 – 146.38	107.99	ok

Values for negative and positive controls were within the range of historical data of the test facility. Therefore, the test system was acceptable.

Assessment

According to OECD Guideline no. 437 (Oct. 2017), a substance with an IVIS ≤ 3 requires no classification for eye irritation or serious eye damage.

Table 8: Classification Scheme

IVIS	UN GHS
≤ 3	No category
> 3 and ≤ 55	No prediction can be made
> 55	Eye damage Category I

In the negative control, no signs of eye irritation were observed.

The positive control induced serious eye damage, which would be classified as GHS category I.

The test item showed effects on the cornea of the bovine eye. The calculated mean IVIS was 3.25.

The experiment is considered valid, because two of the three replicates of the test item lead to the same assessment for the test item.

Interpretation of results:

study cannot be used for classification

Conclusions:

Under the conditions of this ex vivo study (BCOP according to OECD guideline 437; adopted October 2017), a 20 % suspension of ferrous monoglycinate sulfate in HBSS induced a minimal relative increase of the corneal opacity and permeability as compared to negative control. The calculated mean in vitro score was 3.25, which lies in the range of IVIS > 3 and ≤ 55 which does not allow classification according to UH GHS.

Executive summary:

In this ex vivo study according to OECD guideline no. 437 (Oct. 2017, the corneal damage potential of ferrous monoglycinate sulfate was assessed by quantitative measurements of changes in opacity and permeability in a bovine cornea.

Bovine corneas were collected from slaughtered cattle that were between 12 and 60 months old.

The test item was applied onto the cornea of a bovine eye which had been previously incubated with cMEM without phenol red at 32 ± 1 °C for 1 hour and whose opacity had been measured.

The test item was incubated on the cornea for 4 hours at 32 ± 1 °C. After removal of the test item, opacity and permeability values were measured.

Hank’s Balanced Salt Solution (HBSS) was used as negative control. The negative control showed no irritating effect on the cornea and the calculated mean IVIS (In Vitro Irritancy Score) was 2.08.

20 % imidazole solution was used as positive control. The positive control induced serious eye damage on the cornea and was within two standard deviations of the current historical mean. The calculated mean IVIS was 107.99.

Under the conditions of this study, the test item ferrous monoglycinate sulfate showed effects on the cornea of the bovine eye. The calculated mean IVIS was 3.25.

According to OECD Guideline no. 437 (Oct. 2017), a substance with an IVIS > 3 and ≤ 55 induces effects on the cornea, that cannot be classified in an UN GHS Category for eye damage with the BCOP study only. In this case, no prediction can be made.

 

Reference 2

Endpoint:

eye irritation: in vitro / ex vivo

Type of information:

(Q)SAR

Adequacy of study:

supporting study

Study period:

2020

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

results derived from a (Q)SAR model, with limited documentation / justification, but validity of model and reliability of prediction considered adequate based on a generally acknowledged source

Justification for type of information:

1. SOFTWARE
OECD QSAR Toolbox 4.4.1
2. MODEL (incl. version number)
Version 4.4.1
3. SMILES OR OTHER IDENTIFIERS USED AS INPUT FOR THE MODEL
Molecular Structure of chemical formula: C2H5FeNO6S
4. SCIENTIFIC VALIDITY OF THE (Q)SAR MODEL
For detailed information please refer to the attachted justification section
5. APPLICABILITY DOMAIN
For detailed information please refer to the attachted justification section
6. ADEQUACY OF THE RESULT
For detailed information please refer to the attachted justification section

Qualifier:

no guideline followed

Principles of method if other than guideline:

OECD QSAR Toolbox prediction of eye corrosion/irritation

GLP compliance:

no

Irritation parameter:

other: QSAR Toolbox prediction

Vehicle controls validity:

not applicable

Negative controls validity:

not applicable

Positive controls validity:

not applicable

Remarks on result:

other: QSAR Toolbox: According to the Bfr exclusion rules for eye corrosion/irritation ferrous monoglycinate sulfate is not corrosive to the eye based on its physico-chemical properties

Interpretation of results:

other: QSAR prediction

Conclusions:

Using the molecular structure of ferrous monoglycinate sulfate in the QSAR prediction profiler 'BfR exclusion rules' revealed that the substance is not considered to be corrosive to the skin based on its physico-chemical properties.

Executive summary:

There are no data about the corrosivity to the skin of ferrous monoglycinate sulfate. Hence, a QSAR prediction was performed using the OECD QSAR Toolbox and the profiler 'BfR exclusion rules'. Of the rules available, three were met for ferrous monoglycinate sulfate, namely a low LogKow (-3.21), a predicted high melting point (decomp. > 300°C) and a low lipid solubility < 0.01 g/kg. Thus, the substance is not considered to be corrosive.

Endpoint conclusion

Endpoint conclusion:

adverse effect observed (irritating)

Respiratory irritation

Endpoint conclusion

Endpoint conclusion:

no study available

Additional information

In a dermal irritation study performed in accordance with OECD Guideline 439 (In Vitro Skin Irritation) (adopted June 18, 2019), ferrous monoglycinate sulfate (100% a.i.) was applied to the three-dimensional human epidermis model tissue for an exposure period of 1h in triplicates. 25 µL DPBS buffer were topically applied to the epidermal surface in order to improve further contact between the solid and the epidermis. Each approximately 25 mg of the test item were applied to the wetted tissues. The test item was spread to match the surface of the tissue.

After 25 min exposure at room temperture and 35 minutes exposure at 37 ± 1°C and 5.0 ± 1% CO₂and ≥ 95% relative humidity the tissues were washed with DPBS to remove any residual test material. Subsequently the tissue constructs were incubated for 42 h at 37°C. Cytotoxicity (irritancy) was expressed as the reduction of mitochondrial dehydrogenase activity measured by formazan production from MTT at the end of the treatment.

The positive (5% SDS) and negative (DPBS) control gave responses that were within the acceptance criteria and as such demonstrated the validity of the study.

The relative mean tissue viability obtained after 1h treatment with ferrous monoglycinate sulfate compared to the negative control tissues was > 50% (76%). Thus, ferrous monoglycinate sulfate is not classified as irritating to the skin.

In this ex vivo study according to OECD guideline no. 437 (Oct. 2017, the corneal damage potential of ferrous monoglycinate sulfate was assessed by quantitative measurements of changes in opacity and permeability in a bovine cornea.

Bovine corneas were collected from slaughtered cattle that were between 12 and 60 months old.

The test itemwas applied onto the cornea of a bovine eye which had been previously incubated with cMEM without phenol red at 32 ± 1 °C for 1 hour and whose opacity had been measured.

The test item was incubated on the cornea for 4 hours at 32 ± 1 °C. After removal of the test item, opacity and permeability values were measured.

Hank’s Balanced Salt Solution (HBSS) was used as negative control. The negative control showed no irritating effect on the cornea and the calculated mean IVIS (In VitroIrritancy Score) was 2.08.

20 % imidazole solution was used as positive control. The positive control induced serious eye damage on the cornea and was within two standard deviations of the current historical mean. The calculated mean IVIS was 107.99.

Under the conditions of this study, the test itemferrous monoglycinate sulfateshowed effects on the cornea of the bovine eye. The calculated mean IVIS was 3.25.

According to OECD Guideline no. 437 (Oct. 2017), a substance with an IVIS > 3 and ≤ 55 induces effects on the cornea, that cannot be classified in an UN GHS Category for eye damage with the BCOP study only. In this case, no prediction can be made.

Following the ‘New guidance document on an integrated approach on testing and assessment (IATA) for Serious Eye Damage and Eye Irritation’ a second test was started according to OECD guideline 492 to evaluate the eye irritating potential of the substance. The results of this study were not available before registration of the substance, thus, ferrous monoglycinate is classified as at least irritating to the skin. Based on structural alerts gathered with the OECD QSAR Toolbox, some of the BfR exclusion rules are met, according to these, ferrous monoglycinate sulfate is constituted of fragments of which all fragments have a melting point > 200 °C and the lipid solubility is < 0.01g/kg, thus, ferrous monoglycinate sulfate is not considered to be eye corrosive.

 

Justification for classification or non-classification

Based on the currently available data ferrous monoglycinate sulfate is not classified as irritating to the skin but irritating to the eyes Category 2 (causes serious eye irritation) according to Regulation (EU) No. 1272/2008 (CLP) and the Globally Harmonized System for Classification and Labelling of Chemicals (GHS). This classification is based on the first in vitro experiments that were performed, at present testing for eye irritation and skin irritation is repeated following the bottom-up approach as recommended by the New guidance document on an integrated approach on testing and assessment (IATA) for skin corrosion and irritation.

The first experiments showed equivocal results of the single runs, thus, the test item is considered to be non-irritating to the skin andat least causes serious eye damage; eye corrosion will be evaluated by the currently running experiments ordered by the registrant. Based on the physico-chemical properties an additional OECD QSAR Toolbox request regarding structural alerts for eye corrosion/irritation revealed that some of the BfR exclusion rules were met, thus, the substance is not considered to be corrosive. Thus, the substance is classified according to (EU) Regulation 1272/2008 (CLP) and the Globally Harmonized System for Classification and Labelling of Chemicals (GHS) "causes serious eye irritation" Category 2 for precautionary reasons.