Registration Dossier

Diss Factsheets

Toxicological information

Acute Toxicity: dermal

Currently viewing:

Administrative data

Endpoint:
acute toxicity: dermal
Type of information:
experimental study
Adequacy of study:
key study
Study period:
30 May 2012 - 05 July 2012
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
guideline study

Data source

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

Materials and methods

Test guidelineopen allclose all
Qualifier:
according to guideline
Guideline:
OECD Guideline 402 (Acute Dermal Toxicity)
Deviations:
yes
Remarks:
no clinical signs were recorded for animal Y23853 on day 4 by mistake. This deviation was considered not to have compromised the validity or integrity of the study
Qualifier:
according to guideline
Guideline:
EU Method B.3 (Acute Toxicity (Dermal))
Deviations:
yes
Remarks:
no clinical signs were recorded for animal Y23853 on day 4 by mistake. This deviation was considered not to have compromised the validity or integrity of the study
GLP compliance:
yes (incl. QA statement)
Test type:
standard acute method
Limit test:
yes

Test material

Constituent 1
Reference substance name:
Tetramethylthiuram monosulfide
IUPAC Name:
Tetramethylthiuram monosulfide
Constituent 2
Chemical structure
Reference substance name:
Tetramethylthiuram monosulphide
EC Number:
202-605-7
EC Name:
Tetramethylthiuram monosulphide
Cas Number:
97-74-5
Molecular formula:
C6H12N2S3
IUPAC Name:
tetramethylthiuram monosulphide
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: approximately 8 weeks old on the day of treatment .
- Mean body weight at study initiation: the males had a mean body weight of 369 g (range: 358 g to 375 g) and the females had a mean body weight of 234 g (range: 224 g to 254 g).
- Fasting period before study: yes, during the night before treatment.
- Housing: the animals were housed by five from the same sex and group in polycarbonate cages with stainless steel lids .
- Diet: SSNIFF R/M-H pelleted diet (free access)
- Water: tap water filtered with a 0.22 µm filter (free access)
- Acclimation period: the animals were acclimated to the study conditions for a period of 6 or 9 days before treatment.

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.

IN-LIFE DATES: ---- to ----

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): 2000 mg/kg
- Constant volume: no
- For solids, paste formed: no
Duration of exposure:
24h
Doses:
2000 mg/kg.
No. of animals per sex per dose:
5 animals/sex per group
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.
A yellow discoloration was observed at application site of all animals between days 2 and 4.
Erythema and scabs were noted in 2/5 females between days 5 and 14. Scabs were also observed in 1/5 males on days 3 and 4.
Body weight:
Lower mean body weight gain was noted between day 1 and day 8 in females. This was mainly related to one female with lower body weight with 5 g, vs. 36 ± 12 g in controls).
Lower mean body weight gain was noted also observed in males between day 1 and day 8. This was mainly related to body weight loss of 1% (corresponding of -3 g and -5 g from day 1) noted respectively in two males during the first week of the observation period. Their body weight gains returned to normal thereafter.
Gross pathology:
Enlarged spleen was seen in one male treated at 2000 mg/kg. In the absence of similar change in females treated at the same dose-level, this observation in a single male was considered to be unlikely test item related.
Other findings:
no

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

The test item was applied in its original form to the skin of five females and then five males 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. From day 2, any local reactions at the treatment site were also noted. 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 macroscopicpost-mortemexamination.Macroscopic lesions were preservedin buffered formalinthendestroyed at the finalization of the study reportas no microscopic examination was performed.

 

No unscheduled deaths occurred during the study.

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

A yellow discoloration was observed at application site of all animals between days 2 and 4. Erythema and scabs were noted in 2/5 females between days 5 and 14. Scabs were also observed in 1/5 males on days 3 and 4.

When compared to CiToxLAB historical control data, a lower body weight gain was noted in 1/5 females (5 g, vs. 36 ± 12 g in control data base) between day 1 and day 8. In addition, a body weight loss of 1% was noted respectively in 2/5 males during the first week of observation period. Their body weight gains returned to normal thereafter.

No test item-related changes were seen at necropsy.

 

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

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

Categories Display