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:

Read-across concept for sulfites, hydrogensulfites, metabisulfites, dithionites and thiosulfates:

A comprehensive read-across concept has been developed for sulfites, hydrogensulfites and metabisulfites, based on the pH-dependant equilibrium in aqueous solutions which is summarised in the following equations:[1],[2]

           SO2+ H2O <->`H2SO3´         H2SO3<->H++ HSO3-<->2H++SO32-    2HSO3-<->H2O +S2O52-

Since the nature of the cation (i.e., sodium, potassium, ammonium…) is not assumed to contribute substantially to differences in toxicity and solubility (all compounds are very soluble in water), only the chemical and biological properties of the anion are considered as relevant determinants. Based on the described equilibrium correlations, unrestricted read-across between the groups of sulfites, hydrogensulfites and metabisulfites is considered justified.

 

Additionally, it is known that sodium dithionite disproportionates in water to form sodium hydrogen sulfite and sodium thiosulfate (equation II)2,[1], so that this substance can also be considered to be covered by the read-across concept described above. Since it can easily be anticipated that the substance is not stable enough under physiological conditions to fulfil the requirements of study guidelines, instead the products of decomposition have to be considered:

 

       2 S2O42-+ H2O→2HSO3-+ S2O32-

 

Not fully covered by this read-across concept is the substance class of thiosulfates: although the thiosulfates are also well known to disproportionate in aqueous solution to form polythionic acids and SO2(HSO3-), this requires somewhat different, more acidic conditions. Therefore, read-across to sulfites is primarily restricted to appropriate physiological conditions, i.e. oral administration where the gastric passage with the strongly acidic conditions in the stomach will facilitate the chemical disproportionation described above:

 

       HS2O3-+ H2S2O3HS3O3- + SO2+ H2O

 

[1]Hollemann Wiberg, Lehrbuch der Anorganischen Chemie, 101.Auflage

[2]Handbook of Chemistry and Physics, Ed. Lide, DR, 88thedition, CRC Press

One reliable animal study, according to OECD guideline429 (Skin Sensitisation: Local Lymph Node Assay, modified according to Ehlings et al. 2005) and according to GLP has been performed for sodium metabisulfite which shows that the test item has no sensitising properties.

The positive control group caused the expected increases in lymph node cell count (S.I.: 2.427) and lymph node weight (S.I.: 2.160) (statistically significant at p ≤ 0.01). Therefore, the study is regarded as valid. The stimulation index for ear weight was 1.033.


Migrated from Short description of key information:
Based on an existing key study for sodium metabisulfite, it can be concluded that potassium metabisulfite has no senstising properties and must not be classified and labelled according to regulation (EC) No.: 1272/2008. Also, according to the criteria specified by Directive 67/548/EEC and subsequent regulations, the test item is not classified as skin sensitiser.

Respiratory sensitisation

Endpoint conclusion
Endpoint conclusion:
no adverse effect observed (not sensitising)
Additional information:
Migrated from Short description of key information:
There is no evidence on specific respiratory hypersensitivity in test animals following acute inhalation exposure with sodium sulfite. Based on the read-across concept (see `discussion`), potassium metabisulfite is expected to be no respiratory sensitiser.

Justification for classification or non-classification

Skin sensitisation:

(see `discussion`)

The reference Haferkorn (2010) is considered as the key study on skin sensitisation and will be used for classification. The overall sensitisation results are as follows:

Local lymph node assay (LLNA) in mice

Treatment with sodium metabisulfite at concentrations of 10%, 25% or 50% did not reveal statistical significantly increased values for lymph node cell count, all stimulation indices for the lymph node cell count were beneath the threshold value of 1.4. In addition, the lymph node weight was not increased. Hence, the test item is classified as not sensitising.

Under the present test conditions, sodium metabisulfite at concentrations of 10%, 25% and 50% (w/w) in aqua ad iniectabilia did not reveal any sensitising properties in the local lymph node assay.Therefore, the test item must not be classified and labeled accrosing to regulation (EC) No.: 1272/2008. Also, according to the criteria specified by Directive 67/548/EEC and subsequent regulations, the test item is not classified as skin sensitiser.

Based on the read-across concept (see `discussion`), it can be concluded that potassium metabisulfite has no senstising properties and must not be classified and labelled according to regulation (EC) No.: 1272/2008. Also, according to the criteria specified by Directive 67/548/EEC and subsequent regulations, the test item is not classified as skin sensitiser.

Respiratory sensitisation:

There is no evidence on specific respiratory hypersensitivity in test animals following acute inhalation exposure with sodium sulfite. Thus, the classification criteria acc. to regulation (EC) 1272/2008 as respiratory sensitiser are not met.

Based on the read-across concept (see `discussion`), it can be concluded that potassium metabisulfite has no respiratory senstising properties and must not be classified and labelled according to regulation (EC) No.: 1272/2008. Also, according to the criteria specified by Directive 67/548/EEC and subsequent regulations, potassium metabisulfite is not classified as respiratory sensitiser.