Registration Dossier

Administrative data

Description of key information

Key value for chemical safety assessment

Skin sensitisation

Endpoint conclusion
Endpoint conclusion:
no adverse effect observed (not sensitising)
Additional information:

Information on the skin sensitization potential of sulfur is available from three adjuvant based tests (Magnusson and Kligman methodology) and one non-adjuvant investigation (Buehler methodology). All four studies followed OECD guideline 406 and were GLP compliant.

In the first investigation, male and female guinea pigs (albino, NIH (Hartley) strain) were induced by intradermal injection (1% w/v sulfur in saline) and topical application (0.5 g sulfur as a paste in deionised water, applied following treatment with sodium lauryl sulphate) with topical challenge taking place approximately three weeks later (0.5 g sulfur, paste in deionised water) (Rallis Research Centre, 2005). The concentrations used were selected based on results from a preliminary irritancy study, with 2-mercaptobenzothiazole used as a positive control substance. Dermal responses in all groups were assessed using Draize criteria. No erythema or oedema was present in either the control or test groups 24 hr or 48 hr post-challenge while a satisfactory response was obtained in the positive control group. It was concluded that sulfur was not a sensitizer under the conditions of the test.

In a study of essentially similar design, using the same strain of guinea pig, induction treatments comprised intradermal injection of 1% w/v sulfur in paraffin oil followed by topical application of 0.5 g sulfur as a paste in deionised water (applied after SLS treatment of the induction site) (Advinus Therapeutic Private Ltd, 2005). 2-Mercaptobenzothiazole used as a positive control substance and all dermal responses assessed using Draize criteria. No erythema or oedema was present at the challenge site 24 hr or 48 hr post-treatment, while a satisfactory response was obtained in the positive control group. The results confirmed that sulfur is not a dermal sensitizer in the guinea pig maximization test.

In the third adjuvant-based test, 1% w/v sulfur in paraffin oil was selected for intradermal induction and 25% sulfur in ethanol used for topical induction following SLS treatment of the site (RCC Research and Consulting Co., 1994). Animals were challenged/rechallenged 10%, 15% or 25% w/v sulfur in vaselinum album. 4-Aminobenzoic acid ethyl ester was used as a positive control substance. In contrast to the two preceding investigations, erythema and occasional oedema was present in the control and test groups, however responses generally decreased in severity and incidence between the 24 hr and 48 hr observation periods. While responses were more pronounced in the test group relative to the controls, there was little consistency in the extent of response at first challenge and rechallenge for the individual animals with the overall pattern of responses obtained appearing more consistent with non-specific irritation than with sensitization. The results from this study are therefore considered ambiguous and inconclusive with regard to the sensitization potential of sulfur.

In the final study (RCC Research and Consulting Co., 1994), the sensitization potential of sulfur was investigated using a non-adjuvant (Buehler) protocol, with 25% w/v sulfur in vaselinum album selected for topical induction phase and 15% and 25% w/v sulfur in vaselinum album used topical challenge (selection based on results of an irritation screen). 2-Chloro-2,4-dinitrobenzene was used as positive control substance, and dermal responses assessed in all groups using Draize criteria. Slight patchy erythema was commonly present in control animals after challenge/rechallenge with 15% or 25% sulfur, with more pronounced redness present in a majority of test animals. Rechallenge of the same test animals with 15% w/v Thiovit (containing 80% w/w water dispersible sulfur) resulted in moderate erythema after topical application in vaselinum album while no reactions were elicited when distilled water was used a vehicle. While the incidence and extent of responses observed in test animals was greater than that recorded in the controls, the irritant nature of the test substance (as indicated by the occurrence of slight patchy erythema after challenge of the controls) suggests that irritation rather than sensitization was responsible for the responses seen. The results also suggest that the choice of vehicle may influence the response. The results from this study are therefore considered ambiguous and inconclusive regarding to the sensitization potential of sulfur.

In addition to these animal data, a large number of humans are exposed either occupationally or during treatment of skin conditions (acne, seborrheic dermatitis, rosacea, scabies and tinea versicolor). Furthermore, sulfur has been used for many years in cosmetics, veterinary creams, pesticide sprays and dusts/powders. In view of these uses, many individuals have been exposed to sulfur. In all of these applications there is dermal exposure. Human data from the medical examinations conducted at the production plants have shown no incidences of skin sensitization, with some plants being operative for up to 50 years. An extensive review of the literature, concentrating specifically on human data do not indicate a significant number of cases reporting skin sensitization as a consequence of sulfur use for treatment of skin conditions.

Overall, results from two GLP-compliant guideline maximization tests together with extensive human experience indicate that sulfur is not a dermal sensitizer. Skin reactions recorded in other studies appear consistent with irritation, not sensitization.

Migrated from Short description of key information:

Results from four GLP-compliant guideline guinea pig maximisation studies indicate that sulfur is not a dermal sensitiser.

Justification for selection of skin sensitisation endpoint:

One of four available studies.

Respiratory sensitisation

Endpoint conclusion
Endpoint conclusion:
no study available

Justification for classification or non-classification

Sulfur does not meet the criteria for classification as a skin sensitiser according to the criteria of the EU CLP Regulation (EC No. 1272/2008).