Registration Dossier

Administrative data

Endpoint:
acute toxicity: dermal
Type of information:
experimental study
Adequacy of study:
key study
Study period:
2008
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
other: Guideline conform GLP study

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
2008
Report Date:
2008

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
Test type:
standard acute method
Limit test:
yes

Test material

Reference
Name:
Unnamed
Type:
Constituent
Test material form:
other: solid

Test animals

Species:
rat
Strain:
other: HanRcc: WIST(SPF)
Sex:
male/female
Details on test animals and environmental conditions:
TEST ANIMALS
- Source: RCC Ktd. CH-4414 Füllinsdorf, Switzerland
- Age at study initiation: males - 9 weeks; females - 11 weeks
- Housing: individually in Makrolon type-3 cages with standard sofwood bedding
- Diet (e.g. ad libitum): pelleted standard Provimi Kliba 3422 rat/mouse maintenance diet (Provimi Kliba AG, CH-4303 Kaiseraugst/Switzerland), ad libitum
- Water (e.g. ad libitum): community tap water from Füllinsdorf, ad libitum
- Acclimation period:

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 22+/-3°C
- Humidity (%): 30-70%
- Air changes (per hr): 10-15
- Photoperiod (hrs dark / hrs light): 12/12

IN-LIFE DATES: From: 25. June To: 16. July 2008

Administration / exposure

Type of coverage:
semiocclusive
Vehicle:
polyethylene glycol
Details on dermal exposure:
One day before treatment, the backs of the animals were clipped with an electric clipper, exposing an area of approximately 10 % of the total body surface.
Only those animals without injury or irritation on the skin were used in the test.
On test day 1, the test item was applied at a dose of 2000 mg/kg body weight evenly on the intact skin with a syringe and covered with a semi-occlusive dressing. The dressing was wrapped around the abdomen and fixed with an elastic adhesive bandage.
Application volume/kg body weight: 4 mL
Twenty-four hours after the application the dressing was removed and the skin was flushed with lukewarm tap water and dried with disposable paper towels. Thereafter, the reaction sites were assessed.
All animals were re-shaved on test days 8 and 14 to facilitate the reading of the local reactions.
Rationale: Dermal administration was used as this is one possible route of human exposure during manufacture, handling and use of the test item.
Duration of exposure:
24 h, followed by an observation period of 14 days
Doses:
2000 mg/kg bw
Application volume/kg body weight: 4 mL
No. of animals per sex per dose:
Number of Animals per Group: 5 males 5 females
Total number of Animals: 5 males 5 females
Control animals:
no
Details on study design:
Observations
Viability / Mortality: Daily during the acclimatization period, during the first 30 minutes and at approximately 1, 2, 3 and 5 hours after administration on test day 1 (with the clinical signs) and twice daily during days 2-15.
Clinical Signs: Daily during the acclimatization period, during the first 30 minutes and at approximately 1, 2, 3 and 5 hours after administration on test day 1. Once daily during days 2-15.
Local Signs Once daily during days 2-15. All abnormalities were recorded.
Body Weights: On test days 1 (prior to administration), 8 and 15.
Statistics:
No statistical analysis was used.

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: The LD50 after single dermal administration to rats of both sexes, observed over a period of 14 days
Mortality:
No deaths occurred during the study.
Clinical signs:
No clinical or local signs were observed during the course of the study.
Body weight:
The body weight of the animals was within the range commonly recorded for this strain and age.
Gross pathology:
No macroscopic findings were recorded at necropsy.

Applicant's summary and conclusion

Interpretation of results:
not classified
Remarks:
Migrated information Criteria used for interpretation of results: EU
Conclusions:
The median lethal dose of the substance after single dermal administration to rats of both sexes, observed over a period of 14 days is:
LD50 (rat): greater than 2000 mg/kg body weight
Executive summary:

Five male and five female HanRcc:WIST (SPF) rats were treated with the test substance at 2000 mg/kg by dermal application. The test item was diluted in vehicle (PEG 300) at a concentration of 0.5 g/mL and administered at a volume dosage of 4 mL/kg. The application period was 24 hours.

The animals were examined daily during the acclimatization period and mortality, viability and clinical signs were recorded. All animals were examined for clinical signs at approximately 30 minutes, 1, 2, 3 and 5 hours after treatment on day 1 and once daily during test days 2-5. Local signs were noted once daily from test day 2 to 15. Mortality/viability was recorded at approximately 30 minutes, 1, 2, 3 and 5 hours after administration on test day 1 (with the clinical signs) and twice daily during days 2-15. Body weights were recorded on day 1 (prior to administration) and on days 8 and 15. All animals were necropsied and examined macroscopically.

No deaths occurred during the study.

No clinical or local signs were observed during the course of the study.

The body weight of the animals was within the range commonly recorded for this strain and age.

No macroscopic findings were observed at necropsy.

The median lethal dose of the test item after single dermal administration to rats of both sexes, observed over a period of 14 days is LD50 (rat): greater than 2000 mg/kg body weight.