Bis(piperidinothiocarbonyl) hexasulphide

Acute Toxicity: dermal

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 guideline

Test guideline 1

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).

Test guideline 2

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

Test material information

Constituent 1

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:

[(piperidine-1-carbothioylsulfanyl)disulfanyl]disulfanyl piperidine-1-carbodithioate

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:

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

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.