Registration Dossier

Administrative data

Endpoint:
acute toxicity: dermal
Type of information:
experimental study
Adequacy of study:
key study
Study period:
From 2010-09-28 to 2010-10-20
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
guideline study

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
2010
Report Date:
2010

Materials and methods

Test guideline
Qualifier:
according to
Guideline:
OECD Guideline 402 (Acute Dermal Toxicity)
GLP compliance:
yes (incl. certificate)
Test type:
standard acute method
Limit test:
yes

Test material

Reference
Name:
Unnamed
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: Janvier, Le Genest-Saint-Isle, France
- Age at study initiation: 8 weeks old
- Weight at study initiation: 322 ± 9g for the males and 212 ± 11g for the females
- Fasting period before study: the animals were fasted during the night before treatment but had free access to water.
- Housing: The animals were housed in polycarbonate cages with stainless steel lid. During the acclimation period, each cage (43 cm x 22 cm x 20 cm) contained one to seven animals of the same sex. During the treatment period, the animals were housed individually in smaller cages (35.5 cm x 23.5 cm x 19.3 cm).
- Diet (e.g. ad libitum): ad libitum (SSNIFF R/M-H pellet diet)
- Water (e.g. ad libitum): ad libitum
- Acclimation period: 5 days

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): 12h/12h

IN-LIFE DATES: no data

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

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 bw. The quantity of test item applied to each animal was adjusted according to the body weight recorded on the day of dose application.
- Constant volume or concentration used: no
- For solids, paste formed: The test item was placed on an area on the hydrophilic gauze pad pre-moistened with 2 mL of purified water, which was then applied to the skin.
Duration of exposure:
24 hours
Doses:
2000 mg/kg bw
No. of animals per sex per dose:
Ten Sprague-Dawley 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
Statistics:
None

Results and discussion

Effect levels
Key result
Sex:
male/female
Dose descriptor:
LD0
Effect level:
>= 2 000 mg/kg bw
Based on:
test mat.
Mortality:
No deaths were observed during the study.
Clinical signs:
No clinical signs were observed during the study.
Body weight:
When compared to laboratory historical control data, a lower body weight gain was noted in 2 out of 5 males all over the observation period (34 and 26 g vs. 47 ± 7 g in control database between days 1 and 8 then 38 and 41 g vs. 51 ± 8 g in control database between days 8 and 15) and in another male between day 1 and 8 (34 g vs. 47 ± 7 g in control database). The body weight gain of the last returned to normal thereafter. The body weight of the other animals was not affected by the treatment with the test substance.
Gross pathology:
At necropsy, no apparent abnormalities were observed in any animals.
Other findings:
Erythema was noted in 1 out 5 males on day 2 only.

Any other information on results incl. tables

 

 

Applicant's summary and conclusion

Interpretation of results:
GHS criteria not met
Conclusions:
The dermal LD0 of the test substance was equal or higher than 2000 mg/kg bw.
Executive summary:

In a dermal acute toxicity study, the toxicity of the test substance was evaluated following a single dermal application to Sprague-Dawley rats according to OECD No. 402 guideline. The study was conducted in compliance with the principles of Good Laboratory Practice.

The test substance was applied in its original form for 24 hours to the skin of five males and five females Sprague-Dawley rats at the dose level of 2000 mg/kg bw. Then the site of application was covered by a semi-occlusive dressing.

Each animal was observed at least once a day for mortality and clinical signs for a period of up to 14 days following the single administration. From day 2, any local reaction at the treatment site was noted. The body weight of the animals was recorded on the day of treatment and then on days 8 and 15 for the surviving animals.

At the end of the observation period, all surviving animals were sacrified by carbon dioxide asphyxiation and a macroscopic post-mortem examination was performed on all animals.

No deaths and no clinical signs were observed during the study. Erythema was noted in 1 out of 5 males on day 2 only.

When compared to laboratory historical control data, a lower body weight gain was noted in 2 out of 5 males all over the observation period and in another male between days 1 and 8. The body weight gain of the last returned to normal thereafter. The body weight of the other animals was not affected by the treatment with the test substance.

At necropsy, no apparent abnormalities were observed in any animals.

The acute dermal LD50 was found greater than 2000 mg/kg bw.