Registration Dossier

Administrative data

Endpoint:
acute toxicity: dermal
Type of information:
experimental study
Adequacy of study:
key study
Study period:
03 February 2012 - 14 March 2012
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:
2012
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: 1,3-Diphenyl-2-thiourea
- Physical state: white powder
- Lot/batch No.: 1012001047
- Analytical purity: 94.2%
- Expiry date: 12 January 2013
- Storage conditions: protected from moisture and heat, at room temperature.

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: approximately 8 weeks old on the day of treatment
- Mean body weight at study initiation: the males had a mean body weight of 348 g (range: 341 g to 359 g) and the females had a mean body weight of 242 g (range: 224 g to 257 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: 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: 14 February 2012 to 14 March 2012.

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: 24 h post-exposure
- Washing: at 24h post-exposure, with a moistened cotton pad

Duration of exposure:
single exposure (24 hours)
Doses:
2000 mg/kg.
No. of animals per sex per dose:
5 animals 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:
LD50
Effect level:
> 2 000 mg/kg bw
Based on:
test mat.
Remarks on result:
other: no mortality
Mortality:
No unscheduled deaths occurred during the study.
Clinical signs:
No clinical signs indicative of systemic toxicity were observed in any animals.
Very slight erythema was recorded at the application site of one female from day 11 to day 13.
No cutaneous reactions were observed in males.
Body weight:
When compared to historical control data, a lower body weight gain was noted in the most of females during whole study and in 3/5 males between days 8 and 15. In addition, a body weight loss of -2 g was noted in females between days 8 and 15.
Gross pathology:
No macroscopic changes were seen at necropsy following a single dermal application of test item in rats at the dose-level of 2000 mg/kg.
Other findings:
no

Applicant's summary and conclusion

Interpretation of results:
not classified
Remarks:
Migrated information Criteria used for interpretation of results: other: Regulation EC 1272/2008
Conclusions:
The dermal LD50 of the test item, 1,3 Diphenyl 2 thiourea, was higher than 2000 mg/kg in rats.
Therefore, the test item is not classified as harmful or toxic toxic by dermal route according to the criteria of CLP Regulation.
Executive summary:

The objective of this study was to evaluate the potential toxicity of the test item, 1,3‑Diphenyl‑2‑thiourea, following a single dermal application to rats.

This study was conductedaccording to OECD (No. 402, 24th February 1987) and EC (No. 440/2008, Part B.3, 30 May 2008) guidelines, and in compliance with the principles of Good Laboratory Practice.

 

Methods

The test item, 1,3‑Diphenyl‑2‑thiourea,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. 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 macroscopic post-mortem examination. No tissues were preserved.

 

Results

No unscheduled deaths occurred during the study.

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

Very slight erythema was recorded at the application site of 1/5 females from days 11 to 13. No cutaneous reactions were observed in males.

Lower body weight gain was recorded in the most of animals.

No macroscopic changes were seen at necropsy.

 

Conclusion

The dermal LD50of the test item, 1,3‑Diphenyl‑2‑thiourea, 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.