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Toxicological information

Acute Toxicity: dermal

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Administrative data

Endpoint:
acute toxicity: dermal
Type of information:
experimental study
Adequacy of study:
key study
Study period:
22 August 2011 - 02 December 2011
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
other: Compliant to GLP and testing guidelines; adequate consistence between data, comments and conclusions.

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:
OECD Guideline 402 (Acute Dermal Toxicity)
Deviations:
no
Qualifier:
according to
Guideline:
EU Method B.3 (Acute Toxicity (Dermal))
Deviations:
no
GLP compliance:
yes (incl. certificate)
Test type:
standard acute method
Limit test:
yes

Test material

Reference
Name:
Unnamed
Type:
Constituent
Details on test material:
- Name of test material: 4-Methylthiosemicarbazide (MTSC)
- Physical state: white powder
- Lot/batch No.: 11012441081
- Analytical purity: 99.74%
- Expiry date: 06 January 2013
- Storage conditions: at room temperature and protected from light and humidity.

Test animals

Species:
rat
Strain:
Sprague-Dawley
Sex:
male/female
Details on test animals 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 (except group five males which were 10 weeks old
- Mean body weight at study initiation: the males had a mean body weight of 377 g (range: 345 g to 423 g) and the females had a mean body weight of 234 g (range: 217 g to 249 g)
- Fasting period before study: yes, during the night before treatment
- Housing: 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: 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: 30 August 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
Duration of exposure:
24 hours.
Doses:
200, 1000 and 2000 mg/kg.
No. of animals per sex per dose:
Groups 1 to 3: one female per group
Groups 4 and 6: 4 females
Groups 5 and 7: 5 males
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:
LD50
Effect level:
> 200 - < 1 000 mg/kg bw
Based on:
test mat.
Mortality:
During the first step, the female given 2000 mg/kg died on day 3. No mortality was observed at 200 mg/kg (one female) and at 1000 mg/kg
(one female).
During the confirmatory step at 1000 mg/kg, 2/4 females and 4/5 males died on day 3. Except for chromodacryorrhea in one male on day 2,
no pre-death clinical signs were observed in any animal.
There were no deaths during the confirmatory step at 200 mg/kg (four females and five males).
In summary, 1/1 female died at 2000 mg/kg, 6/10 rats (2/5 females and 4/5 males) died at 1000 mg/kg and 0/10 rats died at 200 mg/kg.
Clinical signs:
No clinical signs indicative of systemic toxicity were observed in any animal during the study.
No cutaneous reactions were observed in any animal, except for scabs at the application site on days 7 to 10 in 1/5 males given 200 mg/kg.
Body weight:
The mean body weight changes (g) recorded in animals during the confirmatory step at 200 mg/kg and in historical control data.
Body weight was considered to be unaffected by the test item treatment at 200 mg/kg, when compared to historical control data.
Gross pathology:
Macroscopic enlargement of the spleen was noted at the end of the 14-day observation period in 5/5 males and 2/4 females given 200 mg/kg. In the absence of microscopic examination, the cause of this enlargement could not be determined and a relationship to treatment could not be excluded.

Applicant's summary and conclusion

Interpretation of results:
Toxicity Category III
Remarks:
Migrated information Criteria used for interpretation of results: other: Regulation EC n°1272/2008
Conclusions:
The dermal LD50 of the test item was comprised between 200 and 1000 mg/kg in rats.
According to the criteria of CLP Regulation, the test item should be classified category 3 and assigned the signal word "danger" and the hazard statement "H311: Toxic in contact with skin".
Executive summary:

The objective of this study was to evaluate the potential toxicity of the test item following a single dermal application to rats (OECD 402).

 

Methods

The test item was applied in its original form to the skin of Sprague‑Dawley rats.The application site was covered by a semi‑occlusive dressing for 24 hours.

A first step was performed to determine the appropriate dose-level to be administered in a confirmatory step. In this first step, three females received the dose-level of 200, 1000 or 2000 mg/kg, respectively. As the female given 2000 mg/kg died and as no mortality occurred at 200 and 1000 mg/kg,four other females and then five males received 1000 mg/kg in the confirmatory step. As mortality was observed in males and females at 1000 mg/kg, four females and then five males received 200 mg/kg.

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 days 1, 8 and 15. On completion of the observation period, the animals were sacrificed and submitted for a macroscopicpost-mortemexamination. Macroscopic lesions were preserved but no microscopic examination was performed.

 

Results

The female given 2000 mg/kg and 2/5 females and 4/5 males given 1000 mg/kg died on day 3, without pre‑death clinical signs. No deaths occurred at 200 mg/kg (five females and five males).

No clinical signs indicative of systemic toxicity were observed in any animals, regardless of the dose-level. No cutaneous changes, which could be related to the test item treatment, were noted during the observation period.

Body weight was considered to be unaffected by the test item treatment at 200 mg/kg.

A test item-related enlargement of the spleen at 200 mg/kg could not be ruled out.

Conclusion: The dermal LD50 of the test item was comprised between 200 and 1000 mg/kg in rats.