Diethyl sulphide

Endpoint summary

Description of key information

No in-vivo sensitisation data was identified for diethyl sulphide. An amendment to endpoint 8.3 of Annex VII of REACH requires that alternative methods are used for assessment of skin sensitization potential where these will generate adequate information, therefore, in silico data on Diethyl sulphide using TOPKAT, DEREK, CAESAR and OECD Toolbox predicted this substance not to be a sensitising and no alert for skin sensitisation properties was triggered in Toxtree. The predictions are considered reliable (Pudenz, 2018). Taking additionally into account that structurally similar and not sensitising methyl ethyl sulphide and dimethyl sulphide have the same non-reactive profile as diethyl sulphide, there is a weight of evidence that diethyl sulphide is non-sensitiser. A key read across guideline skin sensitisation study (Olivier, 2004) in guinea pigs was identified to evaluate the skin sensitising potential of methyl ethyl sulphide, a structural analogue of diethyl sulphide. In this guinea pig maximisation study, methyl ethyl sulphide was observed to be not sensitising to the skin of guinea pigs.

Key value for chemical safety assessment

Skin sensitisation

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed (not sensitising)

Additional information:

No key sensitisation data are available for diethyl sulphide. Several criteria justify the use of the read across approach to fill data gaps for diethyl sulphide using methyl ethyl sulphide as an analog. Diethyl sulphide, like methyl ethyl sulphide, is an odorant and has similar physiochemical properties. Hence, the toxicological properties of these substances are also expected to be similar. Key read across data from methyl ethyl sulphide was therefore used to evaluate the skin sensitisation potential.

In a key read across skin sensitisation study (Olivier, 2004; Klimisch score = 1), the potential of methyl ethyl sulphide (a structural analogue of diethyl sulphide) to induce delayed contact hypersensitivity was evaluated in guinea pigs. Thirty guinea pigs were allocated to 2 groups: a control group (5 males/5 females) and a treated group (10 males/10 females). On day 1, 3 pairs of intradermal injections were performed in the interscapular region of all animals: Freund's complete adjuvant (FCA) diluted to 50% (v/v) with 0.9% NaCl (both groups), methyl ethyl sulphide at the concentration of 5% in corn oil (treated group) or vehicle alone (control group), methyl ethyl sulphide at the concentration of 5% in a mixture FCA/0.9% NaCl (50/50, w/w) (treated group) or vehicle at the concentration of 50% (w/v) in a mixture FCA/0.9% NaCl (50/50, v/v) (control group). On day 8, the treated animals received a topical application of the undiluted test item to the same test site, which was then covered under occlusive wrap for 48 hours. The animals of the control group received an application of the vehicle under the same experimental conditions. On day 22, all animals of both groups were challenged by a cutaneous application of the test item at the concentration of 50% (w/w) in acetone to the right flank. The test item was maintained under occlusive wrap for 24 hours. The vehicle was applied to the left flank under the same experimental conditions. Skin reactions were evaluated approximately 24 and 48 hours after removal of the wrap. No systemic clinical signs and no deaths were observed. After the challenge application, no cutaneous reactions were observed in the control group. In the treated group, a discrete erythema was noted on the right treated flank of 1/20 animals at the 24 and 48-hour readings. A discrete erythema was also recorded on the left control flank of 1/20 animals, at the 24-hour reading only. The persistent cutaneous reactions observed in 1/20 animals of the treated group may be attributable to delayed contact hypersensitivity. However, as this possible positive reaction occurred in a single animal, methyl ethyl sulphide should not be considered as a skin sensitiser.

Weight of Evidence by QSAR models run on diethyl sulphide such as CAESAR, DEREK, TOPKAT, Toxtree, OECD Toolbox, Danish QSAR predicted the compound not to be sensitising.

Justification for classification or non-classification

Based on the available in silico data for diethyl sulphide which shows strong evidence that this substance is not sensitising and, a key read across maximisation test with guinea pigs with a structural analog methyl ethyl sulphide where only 1/20 (5%) animals presented a reaction which could attributed to skin sensitisation, it can be said that diethyl sulphide does not meet the criteria for classification as a skin sensitiser under CLP EU Regulation 1272/2008.