Registration Dossier

Administrative data

Description of key information

Key value for chemical safety assessment

Skin sensitisation

Endpoint conclusion
Endpoint conclusion:
no adverse effect observed (not sensitising)
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).

• Animal data:

Stizinger (2010) performed a LLNA assay conducted according to OECD 429 and GLP using up to 50 % of the test item in acetone/olive oil (4:1 v/v). The test item was a 42.6 % solution of FeSO4 in water (plus some impurities). Therefore the final concentration of FeSO4 was about 21.3 % w/w in the applied test solution. Nevertheless this test is regarded suitable for read across to the other iron salts as generally the bioavailability of ferrous iron is higher, while it is rather quickly oxidised in watery solutions to ferric iron and therefore can function as surrogate for the latter. Only for FeCl3 information from two secondary sources (that most probably have the same primary source given the results reported) is available showing an ambiguous picture. As these sources are very unreliable this result is disregarded.

 • Human data

For human data two case reports and a human patch test with 31 volunteers are available. Baer (1973) reports contact sensitization to iron and a positive patch test to a 2 % ferric chloride (FeCl3) solution for a 66-year old white male tool maker. The patient's 5 -year history of allergic contact dermatitis was not associated with any other exposure to metals.

Nater (1960) describes a 44 year old male with eczema-type reactions on his skin in areas that were exposed to steel particles during his job using high pressure cleaning equipment to remove steel particles from construction elements. After testing against 16 other metal salt present in low concentrations in the steel (including nickel and cobalt) and comparing the results to 30 volunteer control people ferric chloride (FeCl3) was identified as the substance triggering sensitising reactions.

Oshima (1991) conducted a human patch test with metals salts from all metals used in a dental clinic. 30 volunteers from the staff of the clinic were tested. All were negative for skin sensitisation effects from the metal salts tested.

• Summary

The available animal data is limited but a fully reliable study on FeSO4 is deemed valid for read across for the other salts of the iron salt category. The available human data are limited. Two cases of skin sensitisation reactions against ferric chloride are reported for two workers that have been highly exposed occupationally through frequent contact with steel products. Nevertheless in one study in 30 individuals no comparable effects were seen. This is in line with the findings of the third available human study where 31 employees of a dental clinic were tested for contact allergy reactions against the metals that they are occupationally exposed to. They were all negative for reactions against metal salts. Finally iron additives are in widespread use as nutritional supplements. If iron ions had a high potency for causing sensitisation this would most probably be realised by now.

Finally it is concluded that in rare cases the development of sensitisation against iron salt is possible. Nevertheless in general iron salts are deemed not to have a potential to cause sensitisation that is relevant for classification.


Migrated from Short description of key information:
Not sensitising; read across from FeSO4 to all other iron salts of this category

Justification for selection of skin sensitisation endpoint:
The study was performed according to OECD TG 429

Respiratory sensitisation

Endpoint conclusion
Endpoint conclusion:
no study available
Additional information:

No specific information on respiratory sensitisation is available. In absence of skin sensitisation and in view of the long occupational use of soluble iron salts, a respiratory sensitisation potential seems unlikely.


Migrated from Short description of key information:
No data indicating sensitisation are available

Justification for classification or non-classification

Skin sensitisation

Pure grades

Based on the above stated assessment of the skin sensitisation potential of iron salts, none of the members of the iron salt category needs to be classified according to Council Directive 2001/59/EC (28th ATP of Directive 67/548/EEC) or 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.

Thus no classification for pure grades of the submission item is required.

Nickel impurity

Possible impurity-triggered classification may however be required depending on the Nickel content: In Annex VI of the 1st ATP to the CLP-Regulation (Commission Regulation (EC) No 790/2009 of 10 August 2009) “nickel sulfate” EC 232-104-9, CAS 7786-81-4, Index no. 028-009-00-5 (Tables 3.1 and 3.2 on pages L 235/11 and 243, respectively) and “nickel dichloride” EC 231-743-0, CAS 7718-54-9 Index no. 028-011-00-6 (Tables 3.1 and 3.2 on pages L 235/135 and 354, respectively) are listed with a specific concentration limit of ≥ 0.01 % w/w triggering classification as skin sensitizing class 1 according to directive 67/548/EWG. The risk phrase R43 (symbol Xi, the indication of danger “Irritant”) or the hazard statement H317 is required according to DSD and CLP, respectively.

Table: Skin sensitisation label elements for category 1 (CLP, 5th ATP, Annex I, 3.4.4.1, Table 3.4.7)

Element

Type

GHS Pictogram

GHS07 exclamation mark

Signal Word

Warning

Hazard Statement

H317: May cause an allergic skin reaction

Precautionary Statements

Prevention

P261, P272, P280

Response

P302 + P352, P333 + P313, P321, P362 + P364 (4th ATP change)

Storage

none

Disposal

P501

Respiratory sensitisation

As no data on respiratory sensitisation 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.