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Administrative data

Description of key information

Based on a positive DEREK NEXUS assessment, Di-2-Hydroxyethyl Disulfide is concluded to have skin sensitising properties (Charles River, 2017a).

The DPRA test for di-2-hydroxyethyl disulfide concluded the test substance to be classified in the “high reactivity class” when using the Cysteine 1:10 / Lysine 1:50 prediction model. The DPRA test was concluded to be valid. The study was conducted according to appropriate OECD Test Guideline and in compliance with GLP (Charles River, 2017b).  

Based on a positive KeratinoSensTM assay, conducted according to appropriate OECD Test Guideline and in compliance with GLP, Di-2-Hydroxyethyl Disulfide is concluded to have skin sensitising properties (Charles River, 2017c).

Based on the DEREK NEXUS assessment, DPRA assay and KeratinoSensTM assay, di-2-hydroxyethyl disulfide is concluded to be a moderate skin sensitizer with a predicted EC3 of 5.1%; no further in vivo testing is considered to be necessary.

(Charles River, 2018).  

Key value for chemical safety assessment

Skin sensitisation

Endpoint conclusion
Endpoint conclusion:
adverse effect observed (sensitising)

Respiratory sensitisation

Endpoint conclusion
Endpoint conclusion:
no study available
Additional information:

A DEREK assessment, DPRA assay and KeratinoSensTM assay were performed in accordance with Section 8.3 of Annex VII of Regulation (EC) No 1907/2006 as amended in Commission Regulation (EU) 2016/1688 of 20 September 2016 and the strategy presented in ECHA Guidance on information requirements and chemical safety assessment Chapter R.7a (Charles River, 2018).  

DEREK NEXUS predicts a potency for skin sensitization for di-2-hydroxyethyl disulfide for the presence of the thiol group. The predicted EC3 based on experimental data for the closest structurally-related substances is 5.1% (moderate sensitizer), which would lead to classification of 1B. The data are not indicative of significant sensitization in humans which would lead to classification Cat 1A and consequently classification of Cat 1B is considered for the skin sensitizing potency prediction of di-2-hydroxyethyl disulfide.

The DPRA test for di-2-hydroxyethyl disulfide concluded the test substance to be classified in the “high reactivity class” when using the Cysteine 1:10 / Lysine 1:50 prediction model. The DPRA test was concluded to be valid. The study was conducted according to appropriate OECD Test Guideline and in compliance with GLP (Charles River, 2017b).  

The objective of this study was to determine the reactivity of Di-2-Hydroxyethyl Disulfide towards model synthetic peptides containing either cysteine (SPCC) or lysine (SPCL). After incubation of Di-2-Hydroxyethyl Disulfide with either SPCC or SPCL, the relative peptide concentration was determined by High-Performance Liquid Chromatography (HPLC) with gradient elution and photodiode array (PDA) detection at 220 nm and 258 nm. SPCC and SPCL Percent Depletion Values were calculated and used in a prediction model which allows assigning the test chemical to one of four reactivity classes used to support the discrimination between sensitizers and non-sensitizers.

No co-elution of the test item with SPCC or SPCL was observed. In the cysteine reactivity assay the test item showed 100.0% SPCC depletion while in the lysine reactivity assay the test item showed 2.3% SPCL depletion. The mean of the SPCC and SPCL depletion was 51.1% and as a result Di-2-Hydroxyethyl Disulfide was classified in the “high reactivity class” when using the Cysteine 1:10 / Lysine 1:50 prediction model. In conclusion, since all acceptability criteria were met this DPRA is considered to be valid. Di-2-Hydroxyethyl Disulfide was positive in the DPRA and was classified in the “high reactivity class” when using the Cysteine 1:10 / Lysine 1:50 prediction model.

Based on a positive KeratinoSensTM assay, conducted according to appropriate OECD Test Guideline and in compliance with GLP, Di-2-Hydroxyethyl Disulfide is concluded to have skin sensitising properties (Charles River, 2017c).

In the first experiment, the maximum luciferase activity induction (Imax) was 3.22-fold. In this experiment, luciferase activity induction (>1.5-fold compared to the vehicle control) was only observed at a cytotoxic concentration (<70% viability compared to the vehicle control).Therefore this induction was not relevant and no EC1.5 was calculated. The test item was retested with a narrower dose response analysis using a lower dilution factor (1.25-fold) to determine if induction also occurs at non-cytotoxic concentrations. A statistically significant induction of the luciferase activity (EC1.5 value 624.1 μM; p<0.001 Student’s t test) was measured in the second experiment. The maximum luciferase activity induction (Imax) was 3.12-fold at 1600 μM. Since the first two experiments obtained different results a third experiment was performed. In the third experiment, a statistically significant induction of the luciferase activity (EC1.5 value 636.4 μM; p<0.001 Student’s t test) was measured. The maximum luciferase activity induction (Imax) was 3.44-fold at 1600 μM. Overall, Di-2-Hydroxyethyl Disulfide is classified as positive in the KeratinoSensTM assay since positive results (>1.5-fold induction) were observed at test concentrations of ≤1000 μM with a cell viability of >70% compared to the vehicle control in two out of three experiments.

The DEREK assessment, DPRA assay and KeratinoSensTM assay all predicted the test item to be a skin sensitizer.

In conclusion, based on the DEREK NEXUS assessment, DPRA assay and KeratinoSensTM assay, di-2-hydroxyethyl disulfide is concluded to be a moderate skin sensitizer with a predicted EC3 of 5.1%; no further in vivo testing is considered to be necessary.

Justification for classification or non-classification

Based on the available in silico, in chemico and in vitro data for di-2-hydroxyethyl disulfide, Cat 1B classification for skin sensitisation is required according to Regulation (EC) No 1272/2008.

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