Registration Dossier

Administrative data

Endpoint:
acute toxicity: dermal
Type of information:
experimental study
Adequacy of study:
key study
Study period:
Feb 2009
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
guideline study

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
2001
Report Date:
2009

Materials and methods

Test guideline
Qualifier:
according to
Guideline:
OECD Guideline 402 (Acute Dermal Toxicity)
Version / remarks:
(1987)
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:
Wistar
Sex:
male/female
Details on test animals and environmental conditions:
TEST ANIMALS
- Strain: HsdCpb: Wu
- Source: Harlan GmbH, 5960 AD Horst, Netherlands
- Age at study initiation: approximately 9-13 weeks
- Weight at study initiation: males 286-298 g; females 223-240 g
- Housing: The animals were caged individually in polycarbonate cages on low dust wood granulate bedding.
- Diet and water: ad libitum
- Acclimation period: at least 5 days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 22 +/- 2
- Humidity (%): 55 +/- 5
- Air changes (per hr): approx. 10
- Photoperiod (hrs dark / hrs light): 12 / 12

Administration / exposure

Type of coverage:
semiocclusive
Vehicle:
unchanged (no vehicle)
Details on dermal exposure:
TEST SITE
One day before the start of the treatment the back and flanks of the rats were shorn (approximately 10 % of the body surface area). For each dose and animal the required amount of the pure liquid test substance was calculated on the base of the body weight at time of dosing. This amount was weighed and applied as uniformly and thinly as possible to the test area, covered with a gauze-layer (6.0 cm x 5.0 cm = 30.0 cm²) of a "Cutiplast steril" coated with "Leukoflex". The gauze strip was placed on the rat's back and secured with a "Lomir biomedical Inc rat jacket", which was connected with a safety pin to the stretch tape to ensure that the animals could not ingest the test substance.

REMOVAL OF TEST SUBSTANCE
After approximately 24 hours the dressings were removed and the area was rinsed with tepid water using soap and gently patting the area dry.
Duration of exposure:
24 hours
Doses:
2000 mg/kg bw per 30.0 cm²
Dose range: males 19.1 - 19.9 mg/cm²; females 14.9 - 16.0 mg/cm².
No. of animals per sex per dose:
5
Control animals:
no
Details on study design:
- Duration of observation period following administration: at least 14 days
- Frequency of observations and weighing: Clinical signs and mortality rates were determined several times on the day of application and subsequently at least once daily. The weight gain of the animals was checked weekly until the end of the study.
- Necropsy of survivors performed: yes
Statistics:
An assessment of the LD50 was made based on the applied dose and dose-response curve, respectively.

Results and discussion

Effect levels
Sex:
male/female
Dose descriptor:
LD50
Effect level:
> 2 000 mg/kg bw
Mortality:
No mortalities occurred.
Clinical signs:
No clinical signs were observed.
Body weight:
There were no toxicologically significant effects on body weight or body weight development in males and females.
Gross pathology:
The necropsies performed at the end of the study revealed no particular findings.

Applicant's summary and conclusion

Executive summary:

An acute dermal toxicity study was performed according to OECD TG 402. For the purpose of a limit test 2000 mg/kg of the test item was applied semiocclusive on 5 male and 5 female rats for 24 hours. No mortalities, no clinical signs, no effects on weight development and no gross pathological findings were observed during the 14 -days observation period. The resulting LD50 was therefore > 2000 mg/kg bw for both sexes combined.