Registration Dossier

Administrative data

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

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)
Version / remarks:
24 February, 1987
Deviations:
no
Qualifier:
according to
Guideline:
EU Method B.3 (Acute Toxicity (Dermal))
Version / remarks:
30 May 2008
Qualifier:
according to
Guideline:
EPA OPPTS 870.1200 (Acute Dermal Toxicity)
Version / remarks:
August 1998
Qualifier:
according to
Guideline:
other: Japan MAFF Testing Guidelin of 12 Nousan No. 8147
GLP compliance:
yes (incl. certificate)
Remarks:
Bioassay, Labor fuer biologische Analytik GmbH, Heidelberg, Germany
Test type:
standard acute method
Limit test:
yes

Test material

Reference
Name:
Unnamed
Type:
Constituent
Test material form:
solid - liquid: suspension
Details on test material:
- Name of test material (as cited in study report): L4-Ligand
- Physical state: white solid
- Analytical purity: 97.0g/100g ± 0.3g/100g
- Lot/batch No.: 0005473663
- Expiration date of the lot/batch: 01 February, 2013
- Storage condition of test material: room temperature, under N2, protected from humidity
- Other: test substance is homogeneous by visual inspection

Test animals

Species:
rat
Strain:
Wistar
Sex:
male/female
Details on test animals and environmental conditions:
TEST ANIMALS
- Source: Charles River Wiga GmbH, Sulzfeld, Germany
- Age at study initiation: male - approximately 8 weeks, female - approximately 12 weeks
- Weight at study initiation: mean (male): 240.6g ± 6.69g, (female): 203.6g ± 6.27g
- Housing: single housing in Makrolon Type III cages
- Diet: VRF1 (P); SDS Special Diets Services, Altrip, Germany
- Water: tap water, ad libitum
- Acclimation period: at least 5 days

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

Administration / exposure

Type of coverage:
semiocclusive
Vehicle:
olive oil
Details on dermal exposure:
TEST SITE
- Area of exposure: 40 cm²
- % coverage: at least 10% of body surface
- Type of wrap if used: air-permeable dressing (4 layers of absorbent gauze) and stretch bandage (Fixomull stretch, adhesive fleece)

REMOVAL OF TEST SUBSTANCE
- Washing: warm water
- Time after start of exposure: 24 hours

TEST MATERIAL
- Amount(s) applied: 3.33 mL/kg bw
- Concentration: 0.6g/mL
- Constant volume or concentration used: yes
- For solids, paste formed: no, suspension used

Duration of exposure:
24 hours
Doses:
2000 mg/kg bw
No. of animals per sex per dose:
5
Control animals:
not required
Details on study design:
- Duration of observation period following administration: 14 days
- Frequency of observations and weighing: observations for clinical signs several times on day of application and once daily hereafter on working days, body weights were determined before application and on day 7 and 14
- Necropsy of survivors performed: yes
- Other examinations performed: clinical signs, body weight, skin findings (scoring was done 30-60 minutes after removal of the dressing and weekly thereafter)
Statistics:
Calculations were performed using Microsoft Excel 2003 and checked with a calculator.

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: no mortalities observed
Mortality:
No mortalities occured.
Clinical signs:
No clinical signs or local effects were observed during the study.
Body weight:
The mean body weight of the male animals increased within the normal range throughout the study period. The mean body weights of the female animals did not significantly change during the post-exposure observation period. This effect is observed at times in the rat strain used, because in the required age range the female animals have already reached the phase of slow growth.
Gross pathology:
No macroscopic pathologic abnormalities were noted in the animals (5 males and 5 females) examined on the last day of observation.

Applicant's summary and conclusion

Interpretation of results:
not classified
Remarks:
Migrated information Criteria used for interpretation of results: EU
Conclusions:
DSD: not classified
CLP: not classified