Disodium 3,3'-dithiobis[propanesulphonate]

Repeated dose toxicity: oral

Administrative data

Endpoint:

repeated dose toxicity: oral

Remarks:

other: subacute and subchronic

Type of information:

migrated information: read-across based on grouping of substances (category approach)

Adequacy of study:

supporting study

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

other: The OECD QSAR Toolbox, is a harmonized system for QSAR application and grouping chemicals into categories, for which OECD principles are met.

Data source

Reference

Reference Type:

other: prediction by the OECD QSAR Toolbox

Title:

Unnamed

Year:

2012

Report date:

2012

Materials and methods

Test guideline

Qualifier:

according to guideline

Guideline:

other: OECD TG 407; OECD TG 422

Deviations:

not applicable

Principles of method if other than guideline:

The prediction is based on the experimental data implemented into the OECD QSAR Toolbox. The chemicals assigned into the category were tested in different long-term toxicity studies.

GLP compliance:

not specified

Test material

Test material information

Constituent 1

Reference substance name:

chemicals assigned into category (The OECD QSAR Toolbox)

IUPAC Name:

chemicals assigned into category (The OECD QSAR Toolbox)

Details on test material:

As Test materials, the chemicals assigned into the category were used.
SMILES ofthe target substance:C(S)CCS(=O)(=O)O{-}.[Na]{+}

Test animals

Species:

other: Rat; Mus musculus; mouse

Strain:

other: SD; albino (Norway, New Zealand strain); F344; Sprague-Dawley; albino (Hebrew University strain); Wistar; B6C3F1;F344/N

Sex:

male/female

Administration / exposure

Route of administration:

oral: gavage

Results and discussion

Effect levels

Dose descriptor:

other: NOEL, LOEL, study LOEL, effect LOEL, study NOEL, NOEL calculated

Effect level:

79.9 mg/kg bw/day (nominal)

Basis for effect level:

other: taking the average from the nearest 7 neighbours, based on 7 values from 7 neighbour chemicals.

Target system / organ toxicity

Critical effects observed:

not specified

Any other information on results incl. tables

The prediction was based on dataset comprised from the following descriptors: NOEL,LOEL,"study LOEL","effect LOEL","study NOEL","NOEL calculated"
Estimation method: Takes average value from the 7 nearest neighbours
Domain logical expression:Result: Out of Domain

("a" and ("b" and "c" and "d" and "e" and "f" and "g" ) )

Domain logical expression index: "a"

Referential boundary: The target chemical should be classified as Thiols (Acute toxicity) by US-EPA New Chemical Categories

Domain logical expression index: "b"

Parametric boundary:The target chemical should have a value of log Kow which is >= -1.02

Domain logical expression index: "c"

Parametric boundary:The target chemical should have a value of log Kow which is <= 2.44

Domain logical expression index: "d"

Parametric boundary:The target chemical should have a value of Molecular weight which is >= 76 Da

Domain logical expression index: "e"

Parametric boundary:The target chemical should have a value of Molecular weight which is <= 182 Da

Domain logical expression index: "f"

Parametric boundary:The target chemical should have a value of Water Solubility which is >= -465 mg/L

Domain logical expression index: "g"

Parametric boundary:The target chemical should have a value of Water Solubility which is <= 9.8E005 mg/L

Applicant's summary and conclusion

Conclusions:

NOAEL of 79.9 mg/kg bw was predicted for the sodium 3-mercaptopropanesulfonic acid.

Executive summary:

Structurally similar substances to 3-mercaptopropanesulfonic acid, sodium salt (CAS 17636 -10 -1) with data on repeated dose toxicity have been searched with the help of the OECD QSAR Toolbox (v.3.0). The prediction was based on the experimental values of chemicals assigned into the category.The target chemical was profiled as "Thiols "Acute toxicity" by the "US EPA New Chemical Categories". Thiols in general are known to conjugate with proteins via protein thiol-disulfide interchange mechanism. They are also capable to bind covalently proteins via a SN2 reaction at a sulphur atom leading to disulfide bridges. These mechanisms of action are relevant for the investigated endpoint. Therefore, primarily a search for chemicals with the same profiling result was performed. The created category comprised of chemicals which data belong to different units (mg/kg/day, mg/kg bw/day, mg/kg nominal etc.). Hence, the current prediction has been run with chemicals with the most data points (...).

The nearest read-across chemicals contain thiol functional groups but no sulfonic groups in their structure. Sulfonic group, however, is not associated with high reactivity as it thiol group does i.e. generation of reactive oxygen species in cells, cysteine peptide depletion or interaction with DNA leading to mutations. Therefore, the category members with thiol groups representing worst case were considered to be suitable for read-across. The chemicals containing other chemical elements in their structure and/or other organic functional groups have not been removed from the domain since they were similar with the target chemical regarding their mechanistic and endpoint specific profiling.

The NOAEL (combined rat and mouse) of read-across chemicals ranged from 28.7 to 504 mg/kg bw. The predicted NOAEL for the target chemical is 79.9 mg/kg bw.

MPS is suitable as a read-across substance for SPS, as data derived from their structural analogues Dimesna and Mesna, which differ only in one –CH₂- group, show that these substances are turning into each other in biological systems, which is in detail outlined in the read-across justification.