Registration Dossier

Toxicological information

Repeated dose toxicity: oral

Currently viewing:

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: rat LD50

Test material

Reference
Name:
Unnamed
Type:
Constituent

Results and discussion

Effect levels

open allclose all
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
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.