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Description of key information

Based on the hydrolysis results (hydrolysis half-life t1/2 < 2 min) and corrosive properties of the substance, a repeated dose oral toxicity study was waived as technically not feasible due to the substances instability in the dosing aqueous solutions/food and animal distress prevention, respectively.

In addition, carcinogenicity data is available on the substance and structurally similar analogue substances.

Key value for chemical safety assessment

Repeated dose toxicity: via oral route - systemic effects

Endpoint conclusion
Endpoint conclusion:
no study available

Repeated dose toxicity: inhalation - systemic effects

Endpoint conclusion
Endpoint conclusion:
no study available

Repeated dose toxicity: inhalation - local effects

Endpoint conclusion
Endpoint conclusion:
no study available

Repeated dose toxicity: dermal - systemic effects

Endpoint conclusion
Endpoint conclusion:
no study available

Repeated dose toxicity: dermal - local effects

Endpoint conclusion
Endpoint conclusion:
no study available

Additional information

Repeated dose toxicity assessed by alternative methods:

Due to ESA instability, there is no adequate data available on repeated dose toxicity. However, this endpoint was assessed by means of in silico modelling to give some supporting information.

To estimate rat chronic LOAEL of ESA, QSAR modelling was performed using the TOPKAT model. 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)

As comparison, the LOAEL value was calculated for the structural similar compound 1,3‑propanesultone (EC 214-317-9, CAS 1120-71-4). The LOAEL value of this carcinogen (harmonised classification as Carc. Cat 1B) was 2 times higher as the LOAEL value of ESA. Again, the prediction was of low reliability due to 8 unknown fingerprint features of the query structure in the training set and the low structural similarity of the four similar compounds (average 0.54).

The rat chronic LOAEL was estimated for heterolysis product of 1,3‑propanesultone, 3‑hydroxypropane sulphonic acid. The predicted LOAEL of cleavage product was 2.3 times higher as the LOAEL of the parent substance 1,3‑propanesultone.

Model

Substance

Prediction (mg/kg bw/day)

Reliability

TOPKAT – chronic LOAEL

1,3-propanesultone

90

Low (8 unknown FPF)

3-hydroxypropanesulphonic acid

203

Low (8 unknown FPF)

This modelling suggested that hydrolysed products of ESA or 1,3propanesultone are of less chronic toxicity than the parent substances. In addition, the LOAEL values of the parent compounds: 47 and 90 mg/kg bw/day for ESA and 1,3-propanesultone, respectively, are in the comparable toxicity range.

Justification for classification or non-classification

The is no adequate study data available to assess classification for Specific Target Organ Toxicity - Repeated Exposure (STOT-RE).

Repeated dose toxicity of ESA was assessed by alternative methods, including QSAR modelling. The chronic LOAEL values were calculated for ESA and its hydrolysis product. Despite of low reliability in the predictions, the chronic LOAEL values showed tendency of less toxicity in the hydrolysed products comparing to the parent compounds. However, this QSAR data is supporting information only and not of high reliability, and therefore cannot be used to assess classification for STOT-RE.