Registration Dossier

Administrative data

Endpoint:
acute toxicity: dermal
Type of information:
experimental study
Adequacy of study:
key study
Study period:
2012-02-16 to 2012-04-16
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
other: GLP compliant study according to OECD TG 402.

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)
Deviations:
no
Qualifier:
according to
Guideline:
EPA OPPTS 870.1200 (Acute Dermal Toxicity)
Deviations:
no
Qualifier:
according to
Guideline:
other: Japan MAFF 8147
Deviations:
no
GLP compliance:
yes (incl. certificate)
Test type:
standard acute method
Limit test:
yes

Test material

Reference
Name:
Unnamed
Type:
Constituent
Test material form:
other: liquid, colorless, clear
Details on test material:
- Name of test material: Acetylmorpholin

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. 12 weeks
- Weight at study initiation: m= mean 229.0 g, f = 207.8 g
- Fasting period before study:
- Housing: single
- Diet: VRF1(P); SDS Special Diets Services, 67122 Altrip, Germany
- Water: ad libitum
- Acclimation period: at least 5 days before the beginning of the experimental phase

ENVIRONMENTAL CONDITIONS
- Temperature: 22 +/- 3 oC
- Humidity: 30-70 %
- Air changes: approx. 10 per hr
- 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.)

IN-LIFE DATES: From: 2012-02-16 To: 2012-03-27

Administration / exposure

Type of coverage:
semiocclusive
Vehicle:
unchanged (no vehicle)
Details on dermal exposure:
TEST SITE
- Area of exposure: about 40 cm2 (corresponds to at least 10% of the body surface)
- Type of wrap if used: The test item was covered with an 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: yes, with warm water
- Time after start of exposure: 24 hrs

TEST MATERIAL
- Amount applied: 1.8 mL/kg bw
- Constant volume or concentration used: yes
Duration of exposure:
24h
Doses:
2000 mg/kg bw
No. of animals per sex per dose:
5 males and 5 females
Control animals:
no
Details on study design:
- Duration of observation period following administration: 14 days
- Frequency of clinical observations: Recording 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.
- Frequency of weighing: Individual body weights shortly before administration (day 0), weekly thereafter and on the last day of observation.
- Necropsy of survivors performed: Yes, gross-pathology examination on the last day of the observation period after sacrifice.
- Mortality: A check for any dead or moribund animals was made at least once each workday.
Statistics:
no

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:
No systemic clinical signs were observed during clinical examination. No local effects were observed.
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 female animals did not adequately 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 abnormalities were detected during necropsy of all animals.
Other findings:
None

Applicant's summary and conclusion