Registration Dossier

Administrative data

Endpoint:
acute toxicity: dermal
Type of information:
experimental study
Adequacy of study:
key study
Study period:
03 November 2011 - 02 December 2011
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
guideline study

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
2011
Report date:
2012

Materials and methods

Test guidelineopen allclose all
Qualifier:
according to guideline
Guideline:
OECD Guideline 402 (Acute Dermal Toxicity)
Deviations:
yes
Remarks:
filtered drinking water was used to moisten the gauze pad for administration and to remove any residual test item (instead of drinking water treated by reverse osmosis).
Qualifier:
according to guideline
Guideline:
EU Method B.3 (Acute Toxicity (Dermal))
Deviations:
no
Remarks:
idem above
GLP compliance:
yes (incl. QA statement)
Test type:
standard acute method
Limit test:
yes

Test material

Constituent 1
Chemical structure
Reference substance name:
Bis(piperidinothiocarbonyl) hexasulphide
EC Number:
213-537-2
EC Name:
Bis(piperidinothiocarbonyl) hexasulphide
Cas Number:
971-15-3
Molecular formula:
C12H20N2S8
IUPAC Name:
1,1'-(hexasulfane-1,6-diyldicarbonothioyl)dipiperidine
Constituent 2
Reference substance name:
Dipentamethylenethiuram hexasulfide
IUPAC Name:
Dipentamethylenethiuram hexasulfide
Test material form:
solid: particulate/powder

Test animals

Species:
rat
Strain:
Sprague-Dawley
Sex:
male/female
Details on test animals or test system and environmental conditions:
TEST ANIMALS
- Source: breeder: Janvier, Le Genest-Saint-Isle, France
- Age at study initiation: on the day of treatment, the animals were approximately 8 weeks old
- Mean body weight at study initiation: the males had a mean body weight of 274 g (range: 268 g to 278 g) and the females had a mean body weight of 216 g (range: 208 g to 224 g)
- Fasting period before study: yes, during the night before treatment
- Housing: polycarbonate cages with stainless steel lid
- Diet: SSNIFF R/M-H pelleted diet (free access)
- Water: tap water filtered with a 0.22 µm filter (free access)
- Acclimation period: at least 5 days before the beginning of the study

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 22 ± 2°C
- Humidity (%): 50 ± 20%
- Air changes (per hr): approximately 12 cycles/hour of filtered, non-recycled air
- Photoperiod (hrs dark / hrs light): 12 h/12 h (7:00 - 19:00)

IN-LIFE DATES: 03 November 2011 to 02 December 2011.

Administration / exposure

Type of coverage:
semiocclusive
Vehicle:
unchanged (no vehicle)
Details on dermal exposure:
TEST SITE
- Area of exposure: 10% of body surface, dorsal site
- Type of wrap if used: hydrophilic gauze pad + adhesive hypoallergenic aerated semi-occlusive dressing + restraining bandage

REMOVAL OF TEST SUBSTANCE
- Removal of dressing: 24h post-exposure
- Washing: at 24h post-exposure, with a moistened cotton pad

TEST MATERIAL
- Amount(s) applied (volume or weight with unit): ----
- Constant volume: no
- For solids, paste formed: ----yes/no----
Duration of exposure:
single exposure (24h)
Doses:
2000 mg/kg
No. of animals per sex per dose:
5 male and 5 females.
Control animals:
no
Details on study design:
- Duration of observation period following administration: 14 days
- Clinical observations: frequently during the hours following treatment; then, at least once a day.
- Body weight: just before treatment on day 1; then on days 8 and 15.
- Necropsy of survivors performed: yes (macroscopic).
Statistics:
no

Results and discussion

Effect levels
Sex:
male/female
Dose descriptor:
LD0
Effect level:
> 2 000 mg/kg bw
Based on:
test mat.
Mortality:
No unscheduled deaths occurred during the study.
Clinical signs:
No clinical signs indicative of systemic toxicity were observed in any animals.
No cutaneous reactions were observed in any animals.
Body weight:
Body weight was unaffected by the test item-treatment when compared to CIT historical control data.
Gross pathology:
At the end of the 14-day observation period, the spleen was enlarged in 4/5 males given the test item at 2000 mg/kg. In view of the absence of similar findings in females treated at the same dose-level, this finding was considered to be incidental and unrelated to the test item administration.

Applicant's summary and conclusion

Interpretation of results:
GHS criteria not met
Conclusions:
The dermal LD50 of the test item was higher than 2000 mg/kg in rats.
Executive summary:

The objective of this study was to evaluate the potential toxicity of the test item following a single dermal application to rats.

This study was conducted in compliance with the principles of Good Laboratory Practice.

 

Methods

The test item Dipentamethylenethiuram hexasulfide was applied in its original form to the skin of five female then five male Sprague-Dawley rats at the dose-level of 2000 mg/kg. The application site was covered by a semi-occlusive dressing for 24 hours.

Each animal was observed at least once a day for mortality and clinical signs for 15 days. Body weight was recorded on day 1 and then on days 8 and 15.

On completion of the observation period, the animals were sacrificed and then submitted for a macroscopic post-mortem examination.Macroscopic lesions were preserved but no microscopic examination was performed.

 

Results

No unscheduled deaths occurred during the study.

No clinical signs indicative of systemic toxicity or cutaneous reactions were observed in any animals.

Body weight was unaffected by the test item treatment.

At the macroscopic examination, enlarged spleen was observed in 4/5 males but this was considered not to be related to the test item.

Conclusion

The dermal LD50of the test item was higher than 2000 mg/kg in rats.

Therefore, the test item is not classified as harmful or toxic by dermal route according to the criteria of CLP Regulation.