Registration Dossier

Administrative data

Endpoint:
acute toxicity: oral
Type of information:
experimental study
Adequacy of study:
key study
Study period:
2008-04-07 to 2008-04-30
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
other: GLP study reliable without restrictions. Minor deviations from the guidelines OECD 420 (2001) and EU Method B.1 bis (2008): - the stability of the test material were missing in the study report. - source of the diet was not stated.

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
2008
Report Date:
2008

Materials and methods

Test guidelineopen allclose all
Qualifier:
equivalent or similar to
Guideline:
EU Method B.1 bis (Acute Oral Toxicity - Fixed Dose Procedure)
Version / remarks:
2008
Deviations:
yes
Remarks:
please refer to "Rationale for reliability incl. deficiencies" above
Qualifier:
according to
Guideline:
OECD Guideline 420 (Acute Oral Toxicity - Fixed Dose Method)
Version / remarks:
2001-12-17
Deviations:
yes
Remarks:
please refer to "Rationale for reliability incl. deficiencies" above
GLP compliance:
yes (incl. certificate)
Remarks:
signed 2007-10-15
Test type:
fixed dose procedure
Limit test:
yes

Test material

Reference
Name:
Unnamed
Type:
Constituent
Details on test material:
- CAS name: Cyclohexanol, 4-(1,1-dimethylethyl)-, trans-
- Molecular formula: C10H20O
- Molecular weight: 156.3 g/miol
- Physical state: solid

Test animals

Species:
rat
Strain:
Sprague-Dawley
Sex:
female
Details on test animals and environmental conditions:
TEST ANIMALS
- Source: Charles River (UK) Ltd, Margate, Kent, UK
- Age at study initiation: eight to twelve weeks of age
- Weight at study initiation: 207 - 228 g
- Fasting period before study: an overnight fast immediately before dosing and for approximately three to four hours after dosing
- Housing: the animals were housed in groups of up to four in suspended solid-floor polypropylene cages furnished with woodflakes.
- Diet (ad libitum; for exception please refer to "Fasting period before study" above): Certified Rat and Mouse Diet
- Water (ad libitum; for exception please refer to "Fasting period before study" above): mains drinking water
- Acclimation period: at least five days

The animals were provided with environmental enrichment items which were considered not to contain any contaminant of a level that might have affected the purpose or integrity of the study.

ENVIRONMENTAL CONDITIONS
- Temperature: 19 to 25°C
- Relative humidity: 30 to 70%
- Air changes: at least fifteen changes per hour
- Photoperiod (hrs dark / hrs light): 12/12

Administration / exposure

Route of administration:
oral: gavage
Vehicle:
DMSO
Details on oral exposure:
VEHICLE
- Justification for choice of vehicle: dimethyl sulphoxide was used because the test material did not dissolve/suspend in distilled water or arachis oil BP.

DOSAGE PREPARATION: for the purpose of the study the test material was freshly prepared, as required, as a solution in dimethyl sulphoxide.

MAXIMUM DOSE VOLUME APPLIED: 10 mL/kg; the volume administered to each animal was calculated according to its fasted bodyweight at the time of dosing.
- concentration: 200 mg/mL

PROCEDURE:
Using the available information on the toxicity of the test material, 2000 mg/kg was chosen as the starting dose. One female rat was dosed with this dose level (sighting study).
In the absence of mortality at a dose level of 2000 mg/kg, an additional group of four animals was treated with the same dose level (main study).






Doses:
2000 mg/kg
No. of animals per sex per dose:
5 female rats (incl. 1 female rat from the sighting study)
Control animals:
no
Details on study design:
- Duration of observation period following administration: 14 days
- Frequency of observations and weighing: clinical observations were made 0.5, 1, 2, and 4 hours after dosing and subsequently once daily for fourteen days. Morbidity and mortality checks were made twice daily.
Individual bodyweights were recorded on Day 0 (the day of dosing) and on Days 7 and 14.
- Necropsy of survivors performed: yes; at the end of the observation period the animals were killed by cervical dislocation. All animals were subjected to gross necropsy. This consisted of an external examination and opening of the abdominal and thoracic cavities. The appearance of any macroscopic abnormalities was recorded. No tissues were retained.
Statistics:
An estimate of the acute oral median lethal dose (LD50) of the test material was made.

Results and discussion

Preliminary study:
One female rat was tested at the dose level of 2000 mg/kg.
Results:
- no death
- hunched posture was noted during the day of dosing and persisted up to three days after dosing. The animal appeared normal four days after dosing.
- the animal showed expected bodyweight gain over the observation period.
- no abnormalities were noted at necropsy.
Effect levels
Sex:
female
Dose descriptor:
LD50
Effect level:
> 2 000 mg/kg bw
Based on:
test mat.
Mortality:
There were no deaths.
Clinical signs:
Main study:
Hunched posture was noted in all animals during the day of dosing.
Animals appeared normal one day after dosing.
Body weight:
Main study:
All animals showed expected gains in bodyweight over the observation period.
Gross pathology:
Main study:
No abnormalities were noted at necropsy.
Other findings:
no other findings

Applicant's summary and conclusion

Interpretation of results:
not classified
Remarks:
Migrated information Criteria used for interpretation of results: EU
Conclusions:
The acute oral median lethal dose (LD50) of the test material in the female Sprague-Dawley CD strain rat was estimated to be greater than 2000 mg/kg bodyweight.
According to the EC-Commission directive 67/548/EEC and its subsequent amendments, the test substance is not classified as acute toxic via the oral route.
According to the EC-Regulation 1272/2008 and its subsequent amendments, the test item is not classified as acute toxic via the oral route.