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Administrative data

Endpoint:
acute toxicity: dermal
Type of information:
experimental study
Adequacy of study:
key study
Study period:
11 Mar 2014 to 27 Mar 2014
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
guideline study

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
Guideline:
OECD Guideline 402 (Acute Dermal Toxicity)
Version / remarks:
Adopted: February 24, 1987
Deviations:
no
Qualifier:
according to guideline
Guideline:
EPA OPPTS 870.1200 (Acute Dermal Toxicity)
Version / remarks:
August 1998
Deviations:
no
Qualifier:
according to guideline
Guideline:
EU Method B.3 (Acute Toxicity (Dermal))
Version / remarks:
30 May 2008
Deviations:
no
GLP compliance:
yes (incl. QA statement)
Test type:
standard acute method
Limit test:
yes

Test material

Constituent 1
Chemical structure
Reference substance name:
bis((1S,2R,6R,7S,8R)-11-(dichloromethylidene)-6-hydroxytricyclo[6.2.1.0²,⁷]undecan-3-one)
EC Number:
941-628-3
Cas Number:
1263184-87-7
Molecular formula:
C12H14Cl2O2
IUPAC Name:
bis((1S,2R,6R,7S,8R)-11-(dichloromethylidene)-6-hydroxytricyclo[6.2.1.0²,⁷]undecan-3-one)
Test material form:
solid

Test animals

Species:
rat
Strain:
Wistar
Remarks:
RccHan (SPF)
Sex:
male/female
Details on test animals or test system and environmental conditions:
TEST ANIMALS
- Age at study initiation: Young adults
- Weight at study initiation: 218-251 g
- Fasting period before study: None
- Housing: Individually in Type II polypropylene/polycarbonate cages. Rodents were housed with deep wood sawdust bedding to allow digging and other normal rodent activities.
- Diet: Autoclavable complete diet for rats and mice – breeding and maintenance, ad libitum
- Water: Tap water ad libitum
- Acclimation period: at least 6 days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 22 ± 3
- Humidity (%): 30-70
- Air changes (per hr): 15-20
- Photoperiod (hrs dark / hrs light): 12/12

IN-LIFE DATES:
11 Mar 2014 to 27 Mar 2014

Administration / exposure

Type of coverage:
semiocclusive
Vehicle:
unchanged (no vehicle)
Remarks:
(moistened with a small amount of water)
Details on dermal exposure:
TEST SITE
- Area of exposure: Back
- % coverage: Approximately 10 % area of the total body surface
- Type of wrap if used: Sterile gauze pads were placed on the skin of rats at the site of application. These gauze pads were kept in contact with the skin by a patch with adhesive hypoallergenic plaster. The entire trunk of the animal was then wrapped with semi occlusive plastic wrap.

REMOVAL OF TEST SUBSTANCE
- Washing: Yes, using body temperature water
- Time after start of exposure: 24 hours

TEST MATERIAL
- Amount applied (volume or weight with unit): 2000 mg/kg bw
- For solids, paste formed: Yes (wetted with a small amount of water)
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 observations / viability and mortality check at 1 and 5 hours after dosing and daily for 14 days thereafter. Body weight recorded prior to dosing on Day 0 and on Days 7 and 14.
- Necropsy of survivors performed: Yes. After examination of the external appearance, the cranial, thoracic and abdominal cavities were opened and the appearance of the tissues and organs were observed. Any gross macroscopic findings were recorded.

Results and discussion

Effect levels
Key result
Sex:
male/female
Dose descriptor:
LD50
Effect level:
> 2 000 mg/kg bw
Based on:
test mat.
Remarks on result:
not determinable due to absence of adverse toxic effects
Mortality:
No mortality occurred during the study.
Clinical signs:
other: There were no adverse clinical signs noted in any animals throughout the study. No treatment related skin irritation was observed in any animal throughout the study.
Gross pathology:
There was no evidence of the test item-related observations at a dose level of 2000 mg/kg bw at necropsy.

Applicant's summary and conclusion

Interpretation of results:
GHS criteria not met
Conclusions:
The median lethal dose after a single dermal administration was found to be greater than 2000 mg/kg bw in male and female RccHan:WIST rat.
Executive summary:

In this GLP compliant, OECD 402 acute dermal absorption study, five male and five female rats (RccHan:WIST) were treated with a single, semi occlusive dermal application of the test substance at a dose of 2000 mg/kg body weight. The test item was wettened and applied as supplied. The application period was 24 hours, followed by a 14-day observation period. Clinical observations along with a check of viability and mortality were performed on all animals at 1 and 5 hours after dosing and daily for 14 days thereafter. Body weight was measured prior to dosing on Day 0 and on Days 7 and 14. Rats were euthanized and subjected to a gross macroscopic examination at the end of the 2-week observation period (Day 14).

No mortality occurred during the 14-day observation period after a 24-hour dermal exposure at 2000 mg/kg bw. No adverse clinical signs were observed after treatment with the test item or during the 14 day observation period and no effects were observed at the site of application. One female animal showed slight body weight loss during the second week of the observation period. There was no evidence of the test item-related observations at a dose level of 2000 mg/kg bw at necropsy.

The median lethal dose (acute dermal LD50) after a single dermal administration was found to be greater than 2000 mg/kg bw in male and female RccHan:WIST rat.