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 ammonium thiosulfate 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.: 1.986) and lymph node weight (statistically significant at p ≤ 0.01). Therefore, the study is regarded as valid. The stimulation index for lymph node weight was 1.844 and for ear weight 1.198.



Migrated from Short description of key information:
Ammonium thiosulfate did not reveal any sensitising properties in the local lymph node assay (modified OECD 429, method according to Ehlings et al. 2005). Based on the read-across approach among thiosulfates, sodium thiosulfate does not require classification as 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 ammonium thiosulfate. Based on the read-across approach, no respiratory sensitising properties for sodium thiosulfate are expected.

Justification for classification or non-classification

Skin Sensitisation:

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

SIs of less than 1.4 (0.546 - 0.940) were observed for lymph node cell count at all test concentrations of ammonium thiosulphate (10, 25, 50 %) and no dose response could be observed..

In addition, SIs of less than 1.1 (0.977 - 1.038) were observed for ear weight at all concentrations ofammonium thiosulphate(10, 25, 50 %).

Thus, the classification criteria acc. to Directive 67/548/EEC and Regulation (EC) 1272/2008 as skin sensitiser are not met.

Based on the read-across approach among thiosulfates, sodium thiosulfate does not require classification as sensitiser.

Respiratory sensitisation

There is no evidence on specific respiratory hypersensitivity in humans following repeated inhalation exposure to ammonium thiosulphate. Furthermore, none of the repeated dose toxicity studies via inhalation reports respiratory hypersensitivity in the test animals. Thus, the classification criteria acc. toDirective 67/548/EECand Regulation (EC) 1272/2008 as respiratory sensitiser are not met.