Registration Dossier

Administrative data

Endpoint:
acute toxicity: dermal
Type of information:
experimental study
Adequacy of study:
key study
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
other: GLP compliant, guideline study, unpublished report available, no restrictions, fully adequate for assessment

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
1994
Report Date:
1994

Materials and methods

Test guidelineopen allclose all
Qualifier:
according to
Guideline:
EPA OPP 81-2 (Acute Dermal Toxicity)
Qualifier:
according to
Guideline:
OECD Guideline 402 (Acute Dermal Toxicity)
GLP compliance:
yes
Test type:
standard acute method
Limit test:
yes

Test material

Reference
Name:
Unnamed
Type:
Constituent
Details on test material:
Trade Name: SULFUR TECHNICAL (SWPF)
Lot Number: 1089 DLD
Supplier: SANDOZ AGRO BP 2, 27600 Gaillon, France
Appearance: Yellow powder
Storage: Room temperature in the dark
Stability: Expiry date of 14-6-1995
A.I. content: Sulfur 100% w/w

Test animals

Species:
rat
Strain:
Wistar
Sex:
male/female
Details on test animals and environmental conditions:
5 male and 5 female Wistar (HanIbm:WIST) rats were obtained from BRL Breeding Laboratories, CH-4414 Fullinsdorf, Switzerland, at approximately 8-9 weeks of age, all individuals being within a weight range of ±10% of the mean value for each sex on delivery. The females were nulliparous and non-pregnant.
Animals were received approximately one week before application. Animals allocated to the study had the fur clipped from the back and were examined by a veterinarian during the acclimatisation period before being authorised for use on the study.

Acclimatisation: approx. 1 week before the application
Housing: 5 per cage in Macrolon size 4 plastic cages with solid bottoms and sifted granular wood provided as bedding
Housing (application): individually housed in size 3 cages
Food: KLIBA pelletted diet no. 24-343-4, (Klingentalmuhle AG. Basel, CH-4303 Kaiseraugst, Switzerland) ad libitum, offered fresh weekly
Water: Municipal supply of Muttenz/BL, ad libitum from polyethylene bottles, offered freshly each week
Light cycle: 12 hours fluorescent light and 12 hours dark per day
Environment: Air-conditioned animal room at 22-23°C, 10-15 air changes per hour, relative humidity 54-59%

Administration / exposure

Type of coverage:
occlusive
Vehicle:
corn oil
Details on dermal exposure:
SULFUR TECHNICAL was administered as a w/w suspension (400 mg/g) in corn oil. The dosing solution was made up on the day of application, maintained in suspension using a magnetic stirrer, and used as soon as possible.
Duration of exposure:
24 hours
Doses:
2000 mg/kg bw (nominal)
2248 mg/kg bw (calculated)
No. of animals per sex per dose:
5 males and 5 females
Control animals:
no
Details on study design:
24 hours before application, the dorsal and ventral fur of each animal was clipped using electric clippers, care being taken not to abrade the skin. The day of dosing was designated day 0. A single dose corresponding to 2 g test material/kg (nominal; 5 g dosing solution/kg) was administered to the skin and to two gauze pads (one layer each) applied to the skin of each animal, using a paintbrush so that at least 10 of the body surface (a minimum area of 6x6 cm up to 250 g bodyweight, or 5x8 cm over 250 g bodyweight) was covered. The treated skin was protected by a piece of plastic secured by binding to prevent ingestion of the test material. The animals remained exposed to the test material for a period of approximately 24 hours, during which they were caged individually. After 24 hours of exposure, the binding was removed, the residual test material washed from the site of application using tap water, and the animals returned to 5 per cage housing.

14 Days after application all surviving were sacrificed.
Observations:
Animals were checked for mortality twice daily (mornings and afternoons, except for weekends when observations were only performed once each day) for a total of 14 days.
Animals were checked for signs of gross ill-health twice daily (mornings and afternoons, except for weekends when observations were only performed once each day) for a total of 14 days. Following dosing, symptoms were recorded during the first hour, then at hours 2-6 after application on the first working day, then twice on the following day (after removal of the bindings), then once daily for a total of at least 14 days.
Animals were weighed on the day of application (day 0) and on days 1-3, 7, 10 and 14.
All animals were subjected to a complete post-mortem examination, which included examination of the following: external surfaces including the application site, all orifices, the cranial cavity and brain, thoracic, abdominal and pelvic cavities with associated organs and tissues, and the neck with its tissues. All abnormalities were recorded.
Statistics:
No statistical analysis was performed.

Results and discussion

Effect levels
Sex:
male/female
Dose descriptor:
LD50
Effect level:
> 2 000 mg/kg bw
Remarks on result:
other: very mild clinical signs at treatment site but no mortality
Mortality:
No mortality was observed.
Clinical signs:
There were no clear signs of toxicity. Slight fur staining around the nose was noted in one female and three male rats during the first 24 hour. Minimal erythema at the application site was observed, and persisted during days 2-5 for 3 female and 4 male rats. Mild skin scaling was seen at the application site in 2/5 females and 5/5 males between days 2-6 and appeared fully reversible.
Body weight:
There were slight losses of bodyweight during the application period. After removal of the binding increases in bodyweight were considered normal.
Gross pathology:
Findings were considered to reflect the normal spectrum of spontaneous lesions present in rats of this strain and age.

Applicant's summary and conclusion

Interpretation of results:
not classified
Remarks:
Migrated information Criteria used for interpretation of results: EU
Conclusions:
Dermal exposure of rats to sulfur, as a suspension in corn oil, for 24hrs at a dose of 2000 mg/kg did not result in any deaths or significant signs of
toxicity. The acute dermal LD50 was > 2000 mg/kg.
Executive summary:

In a GLP compliant OECD guideline 402 dermal acute toxicity study, groups of 5 male and 5 female Wistar rats received a single dermal dose of 2000 mg/kg bw of sulfur, administered as a suspension in corn oil. Clinical signs and bodyweight gain were monitored for 14 days after application, after which the animals were sacrificed and necropsied. No animals died as a result of treatment. Minor clinical signs (nose staining, minimal erythema and scaling at the appilication site) were seen in both male and female rats, and affected animals recovered within 6 days.

The dermal LD50 value for sulfur is higher than 2000 mg/kg bw based on this study.