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:
guideline study

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)
Qualifier:
according to
Guideline:
EPA OPPTS 870.1200 (Acute Dermal Toxicity)
Qualifier:
according to
Guideline:
other: Japan MAFF Testing Guideline of 12 Nosan No. 8147 as this in line with OECD 402.
Qualifier:
according to
Guideline:
EU Method B.3 (Acute Toxicity (Dermal))
GLP compliance:
yes (incl. certificate)
Remarks:
Bioassay Labor für biologische Analytik GmbH
Test type:
standard acute method
Limit test:
yes

Test material

Reference
Name:
Unnamed
Type:
Constituent
Test material form:
solid
Specific details on test material used for the study:
SOURCE OF TEST MATERIAL
- Lot/batch No.of test material: 11-0041
- Test substance No.: 08/0054-4

STABILITY AND STORAGE CONDITIONS OF TEST MATERIAL
- Storage condition of test material: Room temperature

Test animals

Species:
rat
Strain:
Wistar
Sex:
male/female
Details on test animals and environmental conditions:
TEST ANIMALS
- Source: Charles River Wiga GmbH, Sandhofer Weg 7, 97633 Sulzfeld, Germany.
- Age at study initiation: male animals approx. 8 weeks; female animals approx. 10 weeks.
- Weight at study initiation: Males: 225-259 g; Females: 201-219 g (both males and females ± 20% of the mean weight)
- Housing: single housing in Makrolon cage, type III. Fully air-conditioned rooms. Bedding: H 15005-29; Ssniff, Spezialitäten GmbH (Experimental Animal Diets Inc., 59494 Soest, Germany). Enrichment: NGM E-022; ABEDD® LAB & VET Service GmbH, Hasnerstraße 84/6; 1160 Wien – Austria
- Diet: VRF1(P); SDS Special Diets Services, 67122 Altrip, Germany) ad libitum
- Water: Tap water, ad libitum
- Acclimation period: at least 5 days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 22 ± 3
- Humidity (%): 30 – 70
- Photoperiod (hrs dark / hrs light): 12 h / 12 h (6.00 a.m. – 6.00 p.m. / 6.00 p.m. – 6.00 a.m.)

Administration / exposure

Type of coverage:
semiocclusive
Vehicle:
water
Remarks:
Deionized
Details on dermal exposure:
TEST SITE
- Area of exposure: About 40 cm²
- % coverage: At least 10% of the body surface
- Type of wrap: air-permeable dressing (4 layers of absorbent gauze (Ph. Eur. supplied by Lohmann GmbH & Co., KG) and stretch bandage (Fixomull® Stretch (adhesive fleece) supplied by Beiersdorf AG).

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

TEST MATERIAL / VEHICLE
- Amount(s) applied: 4 mL/kg bw
- Concentration: 50 g/100 mL
Duration of exposure:
24 hours
Doses:
A single exposure of 2000 mg/kg bw
No. of animals per sex per dose:
5
Control animals:
no
Details on study design:
- Test item preparation: The test item preparation was produced for the application group shortly before application by stirring with a magnetic stirrer. Additionally the homogeneity of the test item preparation during application was ensured by stirring with a magnetic stirrer.

ANALYSIS
- Conduct of analyses: Samples of the test-item formulation were sent to the sponsor for analysis (BASF SE, Z470, 67056 Ludwigshafen, Germany).
- Stability of the test item preparation: The stability of the test item in the vehicle will determined indirectly by concentration control analysis. For this purpose, the samples taken were stored at room temperature over the maximum duration of the administration period, subsequently deep-frozen and sent to the sponsor for analysis.
- Homogeneity of the test item preparation: The homogeneity of the test item preparation will be determined indirectly by concentration control analysis.
- Concentration control analysis of the test item preparation: A concentration control analysis of the test item preparation and archiving of the respective data will be done by the sponsor.
- Analysis of feed: The feed used in the study was assayed for chemical and microbial contaminants by the manufacturer in quarterly intervals.
- Analysis of drinking water: The drinking water was regularly assayed for contaminants by the municipal authorities of Heidelberg. The German Drinking Water Regulation of Dec. 5, 1990 served as the guideline for maximum tolerable contaminants.
- Bedding and enrichment analysis: The bedding and enrichment were regularly assayed for contaminants (chlorinated hydrocarbons and heavy metals).

EXPERIMENTAL PROCEDURE
- Observation period: 14 days
- Body weight determination: shortly before administration (day 0), weekly thereafter and on the last day of observation.
- Clinical observations: several times on the day of administration, and at least once daily thereafter each workday for the individual animals.
- Scoring of skin findings: Individual readings 30 – 60 minutes after removal of the semi-occlusive dressing (day 1), weekly thereafter and on the last day of observation.
- Mortality: A check for any dead or moribund animals was made at least once each workday.
- Pathology: Necropsy with gross-pathology examination on the last day of the observation period after sacrifice with CO2 in a chamber with increasing concentrations over time.
- Assessment of skin reactions: The evaluation of skin reactions was performed according to Draize, J.H. (1959): Appraisal of the safety of chemicals in foods, drugs and cosmetics. The association of food and drug officials of the United States Austin, Texas.

Results and discussion

Effect levels
Key result
Sex:
male/female
Dose descriptor:
LD50
Effect level:
> 2 000 mg/kg bw
Based on:
test mat.
Mortality:
No mortality occurred.
Clinical signs:
No local or systemic clinical signs were observed during clinical examination.
Body weight:
The mean body weight of the animals increased throughout the study period within the normal range.
Gross pathology:
No macroscopic pathologic abnormalities were noted.

Applicant's summary and conclusion

Interpretation of results:
GHS criteria not met
Conclusions:
In the acute dermal toxicity study, an LD50 value greater than 2000 mg/kg bw in rats was determined.