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other: GLP compliant guideline study, available as unpublished report, no restrictions, fully adequate for assessment

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:
other: Commission Regulation (EC) No 440/2008
Qualifier:
according to
Guideline:
EPA OPPTS 870.1200 (Acute Dermal Toxicity)
Qualifier:
according to
Guideline:
other: Japan MAFF 8147
GLP compliance:
yes (incl. certificate)
Test type:
standard acute method
Limit test:
yes

Test material

Reference
Name:
Unnamed
Type:
Constituent

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: males approx. 9 weeks, females approx. 13 weeks
- Weight at study initiation: males 238-271 g, females 205-218 g
- Housing: single housing in Makrolon cages, type III, with bedding (H 15005-29; Ssniff, Spezialitäten GmbH (Experimental Animal Diets Inc., 59494 Soest, Germany)) and 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 before the beginning of the experimental phase

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 22 ± 3
- Humidity (%): 30 - 70
- Photoperiod (hrs dark / hrs light): 12 / 12

Administration / exposure

Type of coverage:
semiocclusive
Vehicle:
unchanged (no vehicle)
Details on dermal exposure:
TEST SITE
- Area of exposure: 40 cm2
- % coverage: 10
- Type of wrap if used: 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 (if done): warm water
- Time after start of exposure: 24 hours

TEST MATERIAL
- Amount(s) applied (volume or weight with unit): 2.01 mL/kg bw
- Concentration (if solution): undiluted
Duration of exposure:
24 hours
Doses:
2000 mg/kg bw
No. of animals per sex per dose:
5
Control animals:
no
Details on study design:
- Duration of observation period following administration: 14 days
- Frequency of observations and weighing: individual body weights shortly before administration (day 0), weekly thereafter and on the last day of observation; recording of clinical signs several times on the day of administration, and at least once daily thereafter each workday for the individual animals; scoring of skin findings 30 – 60 minutes after removal of the semi-occlusive dressing (day 1), weekly and on the last day of observation; mortality at least once each workday.
- Necropsy of survivors performed: yes

Results and discussion

Effect levels
Sex:
male/female
Dose descriptor:
LD50
Effect level:
> 2 000 mg/kg bw
Based on:
test mat.
Mortality:
No mortality occurred.
Clinical signs:
Systemic effects - No systemic clinical signs were observed during clinical examination.
Local effects - Male animals: Well-defined erythema (grade 2) was observed in all male animals on study day 1 and 2 after application. Thereafter very slight erythema (grade 1) was noted in three out of five animals on study day 5. Very slight edema (grade 1) was noted in 4 male animals on study day 1 and 2. In the remaining male slight edema (grade 2) was observed on study day 1 and very slight edema on study day 2. Furthermore incrustations and scaling were noted in four males between study day 5 and 7.
Local effects - Female animals: Well defined erythema (grade 2) was noted in all female animals on study day 1 and was seen again in four animals on study day 2, while in the fifth animal moderate erythema (grade 3) was observed at the same reading point. On study day 5 after application very slight erythema (grade 1) was noted in all animals. Slight edema (grade 2) was noted in one female on study day 1, but decreased to very slight edema (grade 1) on study day 2. In three out of five females very slight edema was noted on study day 1 and 2 after application. Additionally, incrustations and scaling were noted in all females from study day 5 until day 7 at the latest.
Body weight:
The mean body weight of the male animals increased within the normal range throughout the study period.
The mean body weight of the lightweight female animals did not significantly change during the first post-exposure observation week, probably due to the bandage procedure, but increased during the second week within the normal range.
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