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Description of key information

Sulfur did not induce toxicity in an oral 28 day or an oral 90 day toxicity study up to 1000 mg/kg bw/day.

Regarding dermal exposure, no systemic toxicity was observed up to 1000 mg/kg bw/day in a 28 day study. For dermal local effects, a NOAEL of 400 mg/kg bw/day was derived based on a higher incidence of hyperkeratosis in the treated skin (treatment related and reversible).

Key value for chemical safety assessment

Repeated dose toxicity: via oral route - systemic effects

Endpoint conclusion
Endpoint conclusion:
no adverse effect observed
Dose descriptor:
NOAEL
1 000 mg/kg bw/day
Study duration:
subchronic
Species:
rat

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 adverse effect observed
Dose descriptor:
NOAEL
1 000 mg/kg bw/day
Study duration:
subacute
Species:
rat

Repeated dose toxicity: dermal - local effects

Endpoint conclusion
Endpoint conclusion:
adverse effect observed
Dose descriptor:
NOAEL
400
Study duration:
subacute
Species:
rat
Quality of whole database:
Microscopically the treated skin shows higher incidences of hyperkeratosis in the high dose males and females which was considered treatment related.

Additional information

Oral route

Sulfur was tested in a repeated dose (90 days) oral toxicity study in Wistar rats (OECD guideline 408 and GLP compliant) (Advinus Therapeutics Private Limited 2006). It was administered by oral gavage at doses of 100, 400 and 1000 mg/kg bw/day to low, mid and high dose (including recovery group) groups of rats, respectively. The concurrent control and control recovery group received 0.5% carboxymethyl cellulose containing 0.1% Tween 80 without the test item. Treatment was discontinued for the high dose recovery group at the end of 90th day of treatment. The rats of both the control recovery and high dose recovery group were maintained on normal food for a further 28 days. All the groups consisted of 10 male and 10 female rats.All rats were observed for clinical signs, physical abnormalities, changes in body weights, food consumption and pre-terminal deaths. Haematological and clinical chemistry investigations were performed at sacrifice. The rats were subjected to detailed necropsy at terminal sacrifice and the organs were weighed. Histopathological evaluation was carried out on an extensive range of tissues collected from control and high dose group animals as well as on any gross lesions from lower dose and recovery groups.

No changes of toxicological significance were noted up to the highest tested dose of 1000 mg/kg bw/day. This dose level is considered to be the NOAEL for sulfur in Wistar rats.

 

Regarding the oral route, a 28 day study is also available. In this study, sulfur dust was tested in Wistar rats (OECD guideline 407 and GLP compliant) at doses of 100, 400 and 1000 (including recovery group) mg/kg bw/day (Rallis Research Centre 2005). All the groups consisted of 6 male and 6 female rats. Treatment was discontinued for the high dose recovery group at the end of 28th day of treatment. The rats of both the control recovery and high dose recovery group were maintained on normal food for a further 14 days. All the rats were observed for clinical signs, functional (neurological) observations, changes in body weight and food consumption. Haematological and clinical chemistry investigations were performed at termination. The rats were subjected to a detailed necropsy at sacrifice and liver, adrenals, kidneys, gonads, brain, epididymides, thymus, heart and spleen were weighed. Histopathological evaluation was carried out on the tissues collected from control and high dose group animals together with any gross lesions from the lower dose and recovery groups. The NOAEL in this study was 1000 mg/kg bw/day, as no adverse effects were observed at any dose level.

In conclusion, sulfur did not induce toxicity in an oral 28 day study or an oral 90 day toxicity study at up to 1000 mg/kg bw/day.

 

Dermal route

Sulfur was tested for its dermal toxicity potential in a 28 day study (OECD guideline 410 and GLP compliant) using Wistar rats. The test item was applied at doses of 100, 400 and 1000 mg/kg bw/day (Rallis Research Centre 2006). It was applied as a paste (moistened with de-ionised water) with the dose adjusted based on individual body weight. The paste was transferred on to a cotton gauze pad and applied to a prepared area of skin for 5 days a week for 4 consecutive weeks. A cotton gauze pad moistened with a similar amount of deionised water served as the concurrent vehicle control treatment. The study design included control and high dose recovery groups group, which were maintained for 2 weeks (14 days) after treatment ended. All the rats were observed for clinical signs, local skin reactions, changes in skin/fur, changes in body weight and food consumption. Haematological and clinical chemistry investigations were performed at termination. The rats were subjected to a detailed necropsy at sacrifice and the organs were weighed. Histopathological evaluation was carried out on all the tissues collected from control and high dose group animals and treated skin from all groups, along with any gross lesions present in the lower dose groups and recovery groups.

No systemic effects were observed at any dose level tested. Regarding local effects, a higher incidence of hyperkeratosis (apparent after microscopic examination of treated skin and present in the high dose males and females only) was considered treatment related. This change was considered reversible as in the recovery groups the incidence was nil in high dose recovery males and a single occurrence was present in high dose recovery females.

In view of the results observed, the NOAEL for systemic effects was 1000 mg/kg bw/day. The NOAEL for local dermal effects (irritation) was 400 mg/kg bw/day.

Justification for selection of repeated dose toxicity via oral route - systemic effects endpoint:

One of 2 available studies.

Justification for selection of repeated dose toxicity dermal - systemic effects endpoint:

Only available study.

Justification for selection of repeated dose toxicity dermal - local effects endpoint:

Only available study.

Justification for classification or non-classification

In accordance with the EU CLP Regulation (EC No. 1272/2008), classification is not necessary for repeated dose toxicity based on the available data.