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other: GLP compliant, guideline study, available as unpublished report, no restrictions, fully adequate for assessment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:
2014
Report Date:
2014

Materials and methods

Test guidelineopen allclose all
Qualifier:
according to
Guideline:
OECD Guideline 402 (Acute Dermal Toxicity)
Qualifier:
according to
Guideline:
EU Method B.3 (Acute Toxicity (Dermal))
Qualifier:
according to
Guideline:
EPA OPPTS 870.1200 (Acute Dermal Toxicity)
Qualifier:
according to
Guideline:
other: Japan MAFF 12 Nosan No. 8147
GLP compliance:
yes (incl. certificate)
Remarks:
Bioassay, Labor für biologische Analytik GmbH, Im Neuenheimer Feld 515/519, 69120 Heidelberg
Test type:
standard acute method
Limit test:
yes

Test material

Reference
Name:
Unnamed
Type:
Constituent
Details on test material:
- Name of test material (as cited in study report): Decycloxirane
- Test item No.: 13/0665-1
- Purity: 97.4%/97.3%
- Storage: room temperature
- Physical state/color: liquid/colorless, clear
- Expiry date: July 27, 2014

Test animals

Species:
rat
Strain:
Wistar
Sex:
male/female
Details on test animals and environmental conditions:
TEST ANIMALS
- Source: Charles River Wiga GmbH, Germany
- Age at study initiation: males approx. 8 weeks, females approx. 12 weeks
- Weight at study initiation: mean males 231.2 g, mean females 203.0 g
- Housing: single housing, in Makrolon type III cages; H15005-29 bedding, Ssniff, Spezialitäten GmbH (Experimental Animal Diets Inc., 59494 Soest, Germany); NGM E-022 enrichment, ABEDD® LAB & VET Service GmbH, Hasnerstraße 84/6; 1160 Wien – Austria
- Diet: VRF1(P); SDS Special Diets Services, 67122 Altrip, Germany
- Water: tap water, ad libitum
- Acclimation period: at least 5 days before the experimental phase
- Females were nulliparous and non-pregnant

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 22 ± 3
- Humidity (%): 30 – 70
- Air changes (per hr): 10
- 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: semi-occlusive 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: after removal of the semi-occlusive dressing, the application site was rinsed with warm water
- Time after start of exposure: 24 hours

TEST MATERIAL
- Amount(s) applied (volume or weight with unit): 2.4 mL/kg bw was applied to the clipped epidermis (dorsal and dorsolateral parts of the trunk)
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: Clinical signs for each animal were recorded several times on the day of administration and at least once during each workday thereafter. Individual body weights shortly before administration (day 0), weekly thereafter and on the last day of observation.
- Necropsy of survivors performed: yes
- Scoring of the skin finding: Individual readings 30 – 60 minutes after removal of the semi-occlusive dressing (day 1), several times until the last day of observation.

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 occured.
Clinical signs:
No systemic clinical signs were observed during clinical examination.
Body weight:
The mean body weight of the animals increased within the normal range throughout the study period with one exception in the female group. One female did not gain weight during the first week, but body weights were within the normal range during the second week.
Gross pathology:
No macroscopic pathologic abnormalities were noted in the animals (5 males and 5 females) examined on the last day of observation.
Other findings:
LOCAL EFFECTS:
- Males: Four out of five male animals revealed moderate erythema (grade 3) on day 1 and well-defined erythema (grade 2) from day 2 until day 3. The fifth animal showed moderate erythema from day 1 until day 2 and well-defined erythema on day 3. In all male animals moderate edema (grade 3) occurred on day 1, which decreased to very slight edema (grade 1) from day 2 until day 3. Incrustations were noted in four animals on day 6 and in one animal from day 3 until day 6. Scaling was observed in four animals from day 3 until day 10, 13 or 14, respectively. One animal revealed scaling from day 6 until day 10.
- Females: Four out of five female animals revealed well-defined erythema (grade 2) from day 1 until day 3. The fifth animal showed moderate erythema (grade 3) from day 1 until day 2 and well-defined erythema on day 3.In all female animals moderate edema (grade 3) was observed on day 1 and very slight edema (grade 1) from day 2 until day 3. In all female animals incrustations were noted on study day 6. Scaling was noticed in these animals from day 6 until day 10 or 14, respectively.

Applicant's summary and conclusion