Registration Dossier

Administrative data

Endpoint:
acute toxicity: dermal
Type of information:
experimental study
Adequacy of study:
key study
Study period:
01 June 2012 - 05 July 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)
Qualifier:
according to
Guideline:
EU Method B.3 (Acute Toxicity (Dermal))
GLP compliance:
yes (incl. certificate)
Test type:
standard acute method
Limit test:
yes

Test material

Reference
Name:
Unnamed
Type:
Constituent
Type:
Constituent
Type:
Constituent
Test material form:
solid: particulate/powder

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 350 g (range: 336 g to 359 g) and the females had a mean body weight of 238 g (range: 231 g to 245 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 or 8 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.

IN-LIFE DATES: 12 June 2012 to 29 June 2012.

Administration / exposure

Type of coverage:
semiocclusive
Vehicle:
unchanged (no vehicle)
Remarks:
but premoistened
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:
24 hours
Doses:
2000 mg/kg
No. of animals per sex per dose:
5 anmals per sex.
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).

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:
When compared to CiToxLAB France historical control data, a lower body weight gain was noted in all females (+4 to +16 g vs. 36 ± 12 g in control data base) between day 1 and day 8. Their body weight gain returned to normal thereafter.
Despite a slight lower body weight gain noted in two males (+37 g vs. 45 ± 4 g in control data base) between day 1 and day 8 when compared to CiToxLAB France historical control data, the mean body weight gain of males was unaffected by the test item treatment.
Gross pathology:
No gross findings were observed.

Any other information on results incl. tables

see Executive summary

Applicant's summary and conclusion

Interpretation of results:
not classified
Remarks:
Migrated information CLP Criteria used for interpretation of results: other:
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 objective of this study was to evaluate the potential toxicity of the test item following a single dermal application to rats, following the OECD 402 guideline. This study was conducted in compliance with the principles of Good Laboratory Practice.

 

Methods

The test item was applied in its original form (pre-moistened) 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 and no clinical signs indicative of systemic toxicity were observed in any animals. No cutaneous reactions were observed in any animals. When compared to CiToxLAB historical control data, a lower body weight gain was noted in all females between day 1 and day 8. Their body weight gain returned to normal thereafter. Body weight of males was unaffected by the test item treatment. There were no macroscopic findings in any animals.

Conclusion

The dermal LD50of 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.