Disodium 3,3'-dithiobis[propanesulphonate]

Categories

Category name:

SPS-MPS-MESNA-DIMESNA

Justifications and discussions

Category definition:

In this category, two similarity patterns are combined in order to cover data gaps for SPS. First, there are structural similarities between SPS and Dimesna. Second, a similar degradation of both compounds occurs by which both substances are metabolized to structurally similar compounds, namely MPS and Mesna, respectively. Thus, a so-called many-to-one read-across will be done (two or more analogues are used to make an estimation for a single chemical).

Category description:

Both structurally similar parent compounds, i.e. SPS and Dimesna, degrade similarly into two structurally similar degradation products, i.e. MPS and Mesna.

Category rationale:

REPORTING FORMAT FOR THE CATEGORY APPROACH
For details, please refer to the attached read-across justification. In brief:

1. CATEGORY HYPOTHESIS
There are two category approaches relevant for this category: Chain-length category and similar metabolic pathway.
Chain-length Category: Both SPS and Dimesna are sodium salts of two sulphonated alkanes connected via a disulphide group. SPS contains two propane moieties, Dimesna ethane ones, hence, these chemicals only differ minor in their hydrocarbon chains in one –CH2– group. The same applies to the carbon chain in MPS and MESNA, connecting the sodium sulfonate with the sulfhydryl moiety. The reactivity and toxicological relevance of this difference in chain length is considered to be minor compared to the chemicals properties triggered by the two remaining respective functional groups. Comparing the actually available information on the substances with regard to their physico-chemical properties, the minor influence of the hydrocarbon chain length becomes obvious. The melting points for the disulphide compounds and the sulfhydryl ones are consistent, and the ones for the ethane derivatives are as expected slightly lower. All compounds are very soluble in water, and similar consistencies are noted with regard to vapour pressure and partition coefficient.
Metabolic pathway: Here it is aimed to justify the read-across from both MPS to SPS and Mensa to Dimesna, and Dimesna to SPS and Mesna to MPS (and vice versa) based on the available information on their metabolism.
Generally, Mesna and Dimesna are considered to be a metabolite of each other. Also, other metabolites of Mesna were identified, besides Mesna-Mesna (i.e., Dimesna), such as Mesna-Cys, Mesna-homocysteine, Mesna-cysteinylglutamate, Mesna-cysteinylglycine, and Mesna-GSH which have been collectively termed “Dimesna” in some studies, while others refer to the mixed disulfides containing a single Mesna moiety as “Mesna”, quantifying Dimesna separately. The relevant functional groups for the enzymatic and non-enzymatic metabolism of Dimesna and Mesna are the disulphide resp. thiol functional groups. Those are both contained in the related substances SPS and MPS, which only differ from the former in their hydrocarbon chains in one –CH2– group, the basic structure and functional groups are however identical. Hence, only taking into account the given functional groups, a similar toxicodynamic behaviour of SPS and MPS compared to Dimesna and Mesna can be expected.

2. CATEGORY JUSTIFICATION
As shown above, Mesna, MPS, Dimesna and SPS can be used for read-across to each other by grouping of chemicals. Mesna and MPS and Dimesna and SPS share similar physico-chemical properties as well as they exhibit similar toxicological properties, where data is available. Their alkyl side chains differ only in one –CH2- group, so it can be concluded that e.g. absorption, distribution patterns, or excretion from organ systems and body are comparable. Furthermore, Dimesna and Mesna are considered a metabolite of each other, which allows the conclusion that the same also applies for SPS and MPS. Conclusively, data for Mesna, MPS, and Dimesna can be used to cover data gaps for SPS; especially for the required endpoints for human health assessment.

3. APPLICABILITY DOMAIN OF THE CATEGORY
The members of this category are limited to the four ones mentioned, i.e. Disodium 3,3'-dithiobis [propanesulphonate] (SPS), Ethanesulfonic acid, 2,2'-dithiobis-, disodium salt (DIMESNA), Sodium 3-mercapto propanesulfonate (MPS), and Sodium 2-mercapto ethanesulfonate (MESNA). This is due to the fact that read across is based on “crossover-pairing” of the four members via two different category approaches. For the chain length category, SPS is paired with DIMESNA and MPS with MENSA, whereas with regard to metabolism, MPS is the metabolite of SPS and MESNA of DIMESNA.