1,3,2-dioxathiolane 2,2-dioxide

Repeated dose toxicity: oral

Administrative data

Endpoint:

repeated dose toxicity: oral, other

Remarks:

chronic toxicity predictions

Type of information:

(Q)SAR

Adequacy of study:

supporting study

Reliability:

4 (not assignable)

Rationale for reliability incl. deficiencies:

results derived from a (Q)SAR model, with limited documentation / justification, but validity of model and reliability of prediction considered adequate based on a generally acknowledged source

Justification for type of information:

There is no adequate data available on repeated dose toxicity. However, this endpoint was assessed by means of in silico modelling to give supporting information on chronic toxicity. Chronic LOAEL values were calculated for ESA (1,3,2-Dioxathiolane, 2,2-dioxide) and its hydrolysis product, hydroxyethyl sulphate.

SUBSTANCE:
1,3,2-Dioxathiolane, 2,2-dioxide
CAS: 1072-53-3
EC: 600-809-4
Smiles: S1(OCCO1)(=O)=O

Hydrolysis product:
hydroxyethyl sulphate.
MW: 142.1 g/mol, smiles: OCCOS(=O)(=O)O

MODEL:
TOPKAT - Chronic LOAEL

RELIABILITY:
Low - due unknown fingerprint features of the query structures in the training set and low structural similarity of similar compounds in the model.

Applicability: ESA was within the applicability domain of the TOPKAT model.

ADEQUACY OF THE RESULT :
This modelling suggested that hydrolysed product of 1,3,2-Dioxathiolane, 2,2-dioxide is of less chronic toxicity than the parent substance.

Data source

Reference

Reference Type:

other: QSAR

Title:

Unnamed

Year:

2018

Materials and methods

Test guideline

Qualifier:

no guideline followed

Principles of method if other than guideline:

- Principle of test:
QSAR prediction of chronic toxicity
- Parameters analysed / observed: Chronic LOAEL

Test material

Test material information

Constituent 1

Reference substance name:

1,3,2λ⁶-dioxathiolane-2,2-dione

EC Number:

600-809-4

Cas Number:

1072-53-3

Molecular formula:

C2H4O4S

IUPAC Name:

1,3,2λ⁶-dioxathiolane-2,2-dione

Results and discussion

Effect levels

1

Dose descriptor:

LOAEL

Remarks:

ESA

Effect level:

47 mg/kg bw/day (nominal)

Sex:

not specified

Basis for effect level:

other: Prediction - TOPKAT

Remarks on result:

other: Parent substance

2

Dose descriptor:

LOAEL

Remarks:

hydroxyethyl sulphate

Effect level:

110 mg/kg bw/day (nominal)

Sex:

not specified

Basis for effect level:

other: prediction - TOPKAT

Remarks on result:

other: hydrolysis product

Any other information on results incl. tables

The obtained LOAEL value 47 mg/kg bw/day for ESA was low reliability due to 6 unknown fingerprint features of the query structure in the training set and the low structural similarity of the four similar compounds (average 0.49). However, ESA was within applicability domain of the TOPKAT model.

In addition, the rat chronic LOAEL was estimated for hydrolysis product of ESA, hydroxyethyl sulphate. The predicted LOAEL was 2.3 times higher than the LOAEL of ESA, however with low reliability due to 9 unknown fingerprint features of the query structure in the training set and also the low structural similarity of the four similar compounds (average 0.39).

Model	Substance	Prediction (mg/kg bw/day)	Reliability
TOPKAT – chronic LOAEL	ESA (1,3,2 -Dioxathiolane, 2,2 -dioxide)	47	Low (6 unknown FPF)
	Hydroxyethyl sulphate	110	Low (9 unknown FPF)

Applicant's summary and conclusion

Conclusions:

This modelling suggested that hydrolysed product of ESA is of less chronic toxicity than the parent substance.