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Administrative data

Endpoint:
acute toxicity: oral
Type of information:
experimental study
Adequacy of study:
key study
Study period:
11 Mar 2014 to 08 Apr 2014
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
guideline study
Remarks:
GLP compliant, guideline study, available as unpublished report, no restrictions, fully adequate for assessment.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
Guideline:
OECD Guideline 425 (Acute Oral Toxicity: Up-and-Down Procedure)
Deviations:
no
Qualifier:
according to guideline
Guideline:
EPA OPPTS 870.1100 (Acute Oral Toxicity)
Version / remarks:
December 2002
Deviations:
no
GLP compliance:
yes (incl. QA statement)
Test type:
up-and-down procedure
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
Sex:
female
Details on test animals or test system and environmental conditions:
TEST ANIMALS
- Age at study initiation: 8-10 weeks
- Weight at study initiation: 160-179 g
- Fasting period before study: Overnight prior to treatment
- Housing: Individually in Type II polypropylene/polycarbonate cages. Rodents were housed with deep wood sawdust bedding to allow digging and other normal rodent activities Lignocel bedding for laboratory animals was available to animals during the study
- Diet: Autoclavable complete diet for rats and mice – breeding and maintenance ad libitum (except for pre-dose overnight fast).
- 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 08 Apr 2014

Administration / exposure

Route of administration:
oral: gavage
Vehicle:
water
Remarks:
distilled
Details on oral exposure:
VEHICLE
- Amount of vehicle: 10 mL/kg bw

DOSAGE PREPARATION
Homogeneity of the test item in the vehicle was maintained during administration using a magnetic stirrer.
Doses:
2000 mg/kg bw
No. of animals per sex per dose:
5 females
Control animals:
no
Details on study design:
- Duration of observation period following administration: 14 days
- Frequency of observations and weighing: Clinical observations after 30 mins, 1, 2, 3, 4 and 6 hours after dosing, then once daily thereafter for 14 days. Body weights recorded on days -1 and 0 (prior to dosing), 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. All gross pathological changes were recorded for each animal on the post mortem record sheets.
Statistics:
Data was evaluated using the Acute Oral Toxicity (OECD Test Guidelines 425) Statistical Programme (AOT 425 Stat Pgm).

Results and discussion

Effect levels
Key result
Sex:
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
Clinical signs:
other: Hunched back (2/5) and piloerection (1/5). All animals were symptom free from Day 2 until at the end of the observation period.
Gross pathology:
No treatment-related effects.

Applicant's summary and conclusion

Interpretation of results:
GHS criteria not met
Conclusions:
Under the conditions of this study, the acute oral median lethal dose LD50 of the test item was greater than 2000 mg/kg bw in RccHan:WIST female rats.
Executive summary:

In this GLP compliant, OECD 425 study, the acute toxicity of the test substance was evaluated in a limit test conducted with 5 female rats (RccHan:WIST). Animals were treated with a single oral (gavage) dose of the test substance at a dose level of 2000 mg/kg bw followed by a 14 day observation period. The animals were fasted overnight prior to treatment and food was returned 3 hours after dosing. All animals were observed individually after dosing at 30 minutes, 1, 2, 3, 4 and 6 hours post treatment and once each day for 14 days thereafter. Body weight was measured on Day -1 (prior to removal of food), Day 0 (prior to administration) and weekly thereafter. All animals were examined macroscopically at the end of the study.

There were no deaths and treatment at a dose level of 2000 mg/kg bw caused hunched back (2/5) and piloerection (1/5). All animals were symptom free from Day 2. There were no treatment related changes in the body weights. There was no evidence of the macroscopic observations in animals terminated on Day 14.

Under the conditions of this study, the acute oral median lethal dose LD50 of the test item was greater than 2000 mg/kg bw in RccHan:WIST female rats.