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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 January 2014 -- 21 March 2014
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
guideline study

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
2014
Report Date:
2014

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
Test material form:
liquid

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: 348 g (range: 341 g to 361 g) for the males and 235 g (219 g to 254 g) for the females
- 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

IN-LIFE DATES: 04 March 2014 to 21 March 2014

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

TEST MATERIAL
- Amount(s) applied (volume or weight with unit): 2000 mg/kg
- Constant volume: no
Duration of exposure:
24 hr
Doses:
2000 mg/kg
No. of animals per sex per dose:
Ten rats (five males and five nulliparous and non pregnant 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.
Remarks on result:
no indication of skin irritation up to the relevant limit dose level
Mortality:
No unscheduled deaths occurred during the study.

Clinical signs:
No clinical signs indicative of systemic toxicity were observed in any animals.
A very slight to moderate-to-severe erythema was noted in all males and a very slight to well defined erythema was recorded in all females from Day 2 until Day 6 at the latest. This was associated with very slight to moderate dryness from Day 4 or 5 until Day 13 at the latest in all animals. Scabs were observed in 2/5 males from Day 7 to Day 11.
Body weight:
When compared to historical control data, a higher body weight gain was observed in one male (+57 g vs. +39 ± 11.5 g in control data base) between Days 1 and 8 whereas a lower body weight gain was noted in two males (+35 g and +33 g, respectively, vs. +50 ± 12.0 g in control data base) between Day 8 and Day 15.
A lower body weight gain was observed in two females (+13 g and +14 g, respectively, vs. +25 ± 10.0 g in control data base) between Days 1 and 8. This was followed by a body weight loss of 2 g in one female over the second part of the observation period.
Nevertheless and in absence of marked body weight effect, body weight of animals was considered unaffected by the test item treatment in both sexes when compared to historical control data.
Gross pathology:
The spleen was enlarged in 4/5 males given the test item at 2000 mg/kg. In the absence of macroscopic findings in females given the same dose-level, this finding was considered to be incidental and unrelated to the test item administration.
Other findings:
no

Applicant's summary and conclusion

Interpretation of results:
GHS criteria not met
Remarks:
Migrated information Criteria used for interpretation of results: other: CLP Regulation
Conclusions:
Under the experimental conditions of this study, the dermal LD50 of the test item, was higher than 2000 mg/kg in rats.
Therefore, the test item should not be classified as acutely toxic by dermal route according to the criteria of the 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.

This study was conducted in compliance with OECD Guideline No. 402 and the principles of Good Laboratory Practices.

 

Methods

The test item 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.Macroscopic lesions were preserved in buffered formal in then destroyed at the finalization of the study report as no microscopic examination was performed.

 

Results

No unscheduled deaths occurred during the study.

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

A very slight to moderate-to-severe erythema was noted in all males and a very slight to well-defined erythema was recorded in all females from Day 2 until Day 6. This was associated with very slight to moderate dryness from Day 4 or 5 until Day 13 in all animals. Scabs were observed in 2/5 males from Day 7 to Day 11.

When compared to CiToxLAB France historical control data, a higher body weight gain was observed in 1/5 males (+57 g vs. +39 ± 11.5 g in control data base) between Days 1 and 8 whereas a lower body weight gain was noted in 2/5 males (+35 g and +33 g, respectively, vs. +50 ± 12.0 g in control data base) between Day 8 and Day 15.

A lower body weight gain was observed in 2/5 females (+13 g and +14 g, respectively, vs. +25 ± 10.0 g in control data base) between Days 1 and 8. This was followed by a body weight loss of 2 g in one of them over the second part of the observation period.

Nevertheless and in absence of marked body weight effect, body weight of animals was considered unaffected by the test item treatment in both sexes when compared to CiToxLAB France historical control data.

At the end of the observation period, there were no macroscopic findings at necropsy attributable to the test item administration.

 

Conclusion

Under the experimental conditions of this study, the dermal LD50 of the test item, was higher than 2000 mg/kg in rats.

 

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