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Administrative data

Description of key information

Skin Irritation
For the characterisation of the skin irritation potential of members of the iron salt category, the study of Clouzeau (1994) was chosen as the key study. Based on the results of this study, FeSO4 x 7 H2O was classified as skin irritating – Category 2 according to CLP. This classification for skin irritation is proposed for all members of the iron salt category. Other available skin irritation studies with iron salts were assigned as supporting studies. The tests with FeCl3 and Fe2(SO4)3 support the proposed classification as skin irritant. In the case of FeCl2 the classification due to the precautionary principle represents a worst case. No test data was available for FeClSO4, therefore read across from FeCl3 was proposed, i.e. FeClSO4 should be classified into Category 2 according to CLP.
Eye Irritation / Corrosion
For the characterisation of the eye irritation / corrosion potential of members of the iron salt category, the study of Jeong (2004) was chosen as key study. Based on the results of this study, FeCl2 was classified as causing irreversible effects on the eye – Category 1 according to CLP. This classification for eye irritation / corrosion is proposed for all members of the iron salt category. Other iron salt studies were assigned as supporting studies, where FeCl3 was classified as well into Category 1 according to CLP. An exception was made for FeSO4, which is listed in Annex I of the European Plant Protection Products Directive. This substance is already classified as irritating to eyes (R36) in the Draft Assessment Report for Iron Sulphate (September 2008) and it is proposed to keep this classification for FeSO4. According to CLP, FeSO4 should be classified into Category 2.

Key value for chemical safety assessment

Skin irritation / corrosion

Endpoint conclusion
Endpoint conclusion:
adverse effect observed (irritating)

Eye irritation

Endpoint conclusion
Endpoint conclusion:
adverse effect observed (irritating)

Respiratory irritation

Endpoint conclusion
Endpoint conclusion:
no study available

Additional information

This endpoint is covered by the category approach for soluble iron salts (please see the section Toxicokinetics, metabolism and distribution for the category justification/report format).

Skin Irritation

• Animal data

Key studies

- FeSO4 is considered to be a skin irritating - it is classified as skin irritating Category 2 according to CLP. The result from a fully reliable study conducted according to OECD 404 and GLP in rabbits using FeSO4x7H2O (Clozeau 1994) showed that erythema are formed to an extent that warrant a respective classification for this substance. As in anhydrous FeSO4 the relative amount of iron and sulphate is even higher, it can be assumed that anhydrous iron sulphate is also a skin irritant. The study of Clozeau (1994) is considered as a key study for the iron salt category representing the worst case scenario. Therefore, Category 2 will be assigned to all pure and concentrated iron salts.

CLP (regulation EC No 1272/2008 of the European parliament and of the council, 5th ATP), Annex I, Table 3.2.3 provides the generic concentration limits to be used to determine if the mixture is considered to be an irritant or a corrosive to the skin. Accordingly a mixture, e.g. with water, would need classification if a Category 2 classified component is present in a concentration of ≥10 % unless experimental data on the mixture or a comparable mixture (enabling bridging) exist. Experimental results on watery solution are available from a fully reliable study (Johnson 2003) on 24.9 % (w/w) of FeSO4x7H2O in water. This concentration was no longer a skin irritant and produced no effects. It is thus suggested to replace the generic concentration limit by 25 % (w/w) and to consider aqueous solutions of iron salts as irritant, Category 2, from concentrations of 25 % (w/w) on.

Supporting information

- FeCl3 is deemed skin irritating - Category 2. The result was available from the two supporting studies BASF 1977a and BASF 1977b where rabbits have been exposed to either a 40 % (w/w) solution of FeCl3 in water or to pure, anhydrous FeCl3 for 20 h. In the latter study slight necrosis, desquamation, strong oedema and remnant substance at the test site was seen 24 h post exposure. 8 days after exposure still scabbing, necrosis and desquamation were found. No information is available on the effects 14 days post dosing. Following the precautionary principle based on the available results the substance is deemed a skin irritant Category 2 according to CLP. The results in the study (with 40 % (w/w) solution in water) are comparable but of less severity. The proposed classification as Category 2 skin irritant thus is supported.

- For Fe2(SO4)3 a clear classification based on the available data is not possible. The results from OECD TG 404 and GLP compliant study ICI 1991b suggest that the substance is not irritating. Nevertheless the available methodological information is so scarce that these results are not reliable. In addition the reported findings are surprising as a solution of ferric sulphate has a very low pH value, comparable to a FeCl3 solution with the same concentration of iron. Accordingly here a read across from FeCl3 is applied and the substance is deemed a skin irritant Category 2 according to CLP.

- FeCl2 is deemed not irritating. A fully reliable in vivo study in rabbits (Park 2004) conducted according to OECD 404 and GLP shows that the effects inflicted by FeCl2 (pure, moistened with distilled water) on the rabbit skin at all time-points are clearly below the threshold values that would trigger a classification as skin irritant. According to precaution reasons and category approach, we recommend the worst case scenario and to assign FeCl2 to the Category 2.

- For FeClSO4 no test data is available. As the substance has the same oxidation state as FeCl3 the latter is use as the template for read across. Accordingly FeClSO4 is deemed a skin irritating - Category 2 according to CLP.

• Human data

No relevant human data on skin irritation are available. An overview of existing observation is available from the OECD (2007, p 45) SIDS Initial Assessment Report (SIAR).

  • OECD Organisation for Economic Co-operation and Development (2007). SIDS Initial Assessment Report for SIAM 24. Chemical Category: Iron Salts. Self-published, Paris, France 138 p.

• Summary:

According to the worst case scenario, all pure and concentrate iron salts (>25 %) should be assigned to the skin irritation Category 2.

Eye Irritation / Corrosion

• Animal data

Key study

- FeCl2 is deemed corrosive to the rabbit eye - Category 1 according to CLP based on the results from a fully reliable study (Jeong 2004, according to OECD TG 405 and GLP). Irritation was observed in the cornea, iris and conjunctiva reaching threshold values that clearly trigger the classification. This study was selected as the key study and considered as the worst case scenario for all iron salts included in this category.

Supporting information

- FeCl3 is deemed corrosive to the rabbit eye - Category 1 (according to CLP). The result was available from the two supporting studies BASF 1977a and BASF 1977b where rabbits have been exposed to either 50 µL of a 40 % (w/w) solution of FeCl3 in water or to 50 mg of pure, anhydrous FeCl3. In the latter study at 1 h after the application of the test item to the rabbit eye the palpebral conjunctiva was yellowish stained and slight oedema, strong corneal opacity and discharge was seen. All signs increased in severity after 24 h and 8 days post dosing leading to corneal ablation and suppurative inflammation of the eye. The results in the study conducted with 40 % aqueous solution, are comparable but of less severity than in the study with the pure compound.

- For Fe2(SO4)3 a clear classification based on the available data is not possible. Information is available from only one unreliable secondary source (Grant 1986). No numerical data is given. As a solution of ferric sulphate has a very low pH value, comparable to a FeCl3 solution with the same concentration of iron, here a read across from FeCl3 is applied and the substance is deemed corrosive to the rabbit eye - Category 1 according to CLP.

- For FeClSO4 no test data is available. As the substance has the same oxidation state as FeCl3 the latter is used as the template for read across. Accordingly FeClSO4 is deemed to be corrosive to the rabbit eye - Category 1 according to CLP.

Supplementary information

- According to an EFSA (2008) Draft Assessment Report for Iron Sulphate, FeSO4 is classified as irritating to eyes (R36). A fully reliable study is available (Bayer AG 1992, conducted according to OECD 404 and GLP), using FeSO4 x 7 H2O as test item and indicating that this substance is slightly irritating to the rabbit eye. Due to the water content the data are not fully indicative for the irritation/corrosion potential of anhydrous FeSO4.

Based on the already available documents, FeSO4 is an exception of iron salt category and classified as irritating to eyes - Category 2 according to CLP.

  • EFSA European Food Safety Authority ed (2008) Draft Assessment Report (DAR) – public version – Initial risk assessment provided by the rapporteur member state U.K. for the existing active substance Iron Sulphate of the fourth stage of the review programme referred to in Article 8(2) of Council Directive 91/414/EEC. September 2008. Volumes 1 to 3.

• Human data

No human data on eye irritation are available. Existing information is available from the OECD (2007, p 45) SIDS Initial Assessment Report (SIAR).

  • OECD Organisation for Economic Co-operation and Development (2007). SIDS Initial Assessment Report for SIAM 24. Chemical Category: Iron Salts. Self-published, Paris, France 138 p.

• Summary:

All iron salts in this category are deemed to produce corrosivity in the eye and are classified as follows: irreversible effects on the eyes - Category 1 according to CLP. Exception is FeSO4 which is already classified in the Draft Assessment Report for Iron Sulphate (September 2008) as irritating to eyes - Category 2 according to CLP.

Respiratory irritation

• Animal data

Only one data source is available on this endpoint. The American Conference of Governmental Industrial Hygienists stated in one of their reports from 1980 (ACGIH 1980) that the inhalation of ferric salts as dusts and mists is irritating to the respiratory tract. Quantitative data that would allow a solid decision on the need for classification is not available. The reliability of this information is low.

• Human data:

In a pre-GLP study (Kleinman 1981) the respiratory effects of inhalation exposure to ferric sulphate aerosol were studied in humans (reliability score 2) volunteers (38) were exposed to 75 µg/m³ aerosol of ferric sulphate (= 20 µg/m³ Fe) for 2 hours on each of 5 days. The investigation was conducted as a double blind study. Subjects served as their own control by blind exposure to sham aerosol. The group average results were contrasted between day (sham or exposure) and conditions (pre- and post-exposure) using a two-way analysis of variance with repeated measure. Only five of the 38 volunteers tested showed patterns indicative of a decrement in pulmonary function. Nine of the subjects exhibited significant improvement in function. None of the subjects reported more than slight changes in symptoms during exposure. The authors considered that the tendency for a subject to improve after the ferric sulphate exposure could be related to allergy status, smoking history, or a combination of these factors. Furthermore, they recorded that “it is encouraging to note that at the relatively high aerosol concentration used in this study, there were no significant detrimental changes in the (study) population as a whole.” The study appears to have been well conducted and the conclusions are consistent with the data presented. It may be assumed that ferric sulphate aerosols do not produce any clear pulmonary effects in either normal persons or asthmatics.

• Summary:

The available data are not sufficient to allow decision on classification for the endpoint respiratory irritation.


Justification for selection of skin irritation / corrosion endpoint:
Reliable study conducted according to OECD TG 404 and GLP in rabbits using FeSO4.7H2O

Justification for selection of eye irritation endpoint:
Reliable study conducted according to OECD TG 405 and GLP in rabbits using FeCl2

Effects on skin irritation/corrosion: irritating

Effects on eye irritation: corrosive

Justification for classification or non-classification

Skin irritation / corrosion:

Based on the above stated assessment of the skin irritation / corrosion tests of the iron salts, the results from reliable studies or from read across show that the iron salts of this category are skin irritants, except for FeCl2 (Park & Seong 2004). Accordingly the salts belonging to the iron salt category, except FeCl2, need to be classified as “R38 Irritating to skin” according to Council Directive 2001/59/EC (28th ATP of Directive 67/548/EEC) and as Category 2, “Warning - H315: Causes skin irritation” according to CLP (5th ATP of Regulation (EC) No 1272/2008 of the European Parliament and of the Council) as implementation of UN-GHS in the EU.

Category members except Ferrous chloride

Table: Skin corrosion/irritation label elements for category 2 (CLP, 5th ATP, Annex I, 3.2.4.1, Table 3.2.5)

Element

Type

GHS Pictogram

GHS07 exclamation mark

Signal Word

Warning

Hazard Statement

H315: Causes skin irritation

Precautionary Statements

Prevention

P264, P280

Response

P302 + P352, P321, P332 + P313, P362 + P364 (4th ATP change)

Storage

none

Disposal

none

Ferrous chloride

No classification for skin irritation/corrosion is required.

Eye irritation / corrosion:

Category members except Ferrous sulphate

Based on the above stated assessment of the eye irritation /corrosion tests of the iron salts, the results from reliable studies or from read across show that the iron salts of this category are corrosive to the eye, except for FeSO4. Accordingly the salts belonging to the iron salt category need to be classified as “R41 Risk of serious damage to eyes” according to Council Directive 2001/59/EC (28th ATP of Directive 67/548/EEC) and as Category 1, “Danger - H318: Causes serious eye damage“ according to CLP (5th ATP of Regulation (EC) No 1272/2008 of the European Parliament and of the Council) as implementation of UN-GHS in the EU.

Table: Serious eye damage/eye irritation label elements for category 1 (CLP, 5th ATP, Annex I, 3.3.4.1, Table 3.3.5)

Element

Type

GHS Pictogram

GHS05 corrosive

Signal Word

Danger

Hazard Statement

H318: Causes serious eye damage

Precautionary Statements

Prevention

P280

Response

P305 + P351 + P338, P310

Storage

none

Disposal

none

Ferrous sulphate

FeSO4 is already classified as irritating to eyes (R36) in the Draft Assessment Report for Iron Sulphate (September 2008) and it is proposed to keep this classification for FeSO4. According to CLP, FeSO4 should be classified into Category 2.

Table: Serious eye damage/eye irritation label elements for category 2 (CLP, 5th ATP, Annex I, 3.3.4.1, Table 3.3.5)

Element

Type

GHS Pictogram

GHS07 exclamation mark

Signal Word

Warning

Hazard Statement

H319: Causes serious eye irritation

Precautionary Statements

Prevention

P264, P280

Response

P305 + P351 + P338, P337 + P313

Storage

none

Disposal

none

Respiratory irritation:

As no reliable data on respiratory irritation is available for iron salts a classification is not possible according to Council Directive 2001/59/EC (28th ATP of Directive 67/548/EEC) and according to CLP (5th ATP of Regulation (EC) No 1272/2008 of the European Parliament and of the Council) as implementation of UN-GHS in the EU.