Cyclohexyl phenyl ketone

Acute Toxicity: oral

Administrative data

Endpoint:

acute toxicity: oral

Type of information:

experimental study

Adequacy of study:

key study

Study period:

From Jun. 19, 2003 to Aug. 26, 2003

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

other: Well documented, according to accepted guidelines

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

2003

Report date:

2003

Materials and methods

Test guideline

Test guideline 1

Qualifier:

according to guideline

Guideline:

OECD Guideline 423 (Acute Oral toxicity - Acute Toxic Class Method)

Version / remarks:

2001

Deviations:

yes

Remarks:

- Acclimatization period not reported.

Test guideline 2

Qualifier:

according to guideline

Guideline:

EU Method B.1 tris (Acute Oral Toxicity - Acute Toxic Class Method)

Version / remarks:

1996

Deviations:

yes

Remarks:

- Acclimatization period not reported.

GLP compliance:

yes (incl. QA statement)

Remarks:

- Switzerland

Test type:

acute toxic class method

Limit test:

yes

Test material

Test material information

Constituent 1

Reference substance name:

Cyclohexyl phenyl ketone

EC Number:

211-923-5

EC Name:

Cyclohexyl phenyl ketone

Cas Number:

712-50-5

Molecular formula:

C13H16O

IUPAC Name:

cyclohexyl(phenyl)methanone

Details on test material:

- Name of test material (as cited in study report): TK A 40293 Cyclohexylphenylketon.
- Physical state: Yellow solid.
- Analytical purity: 98%.
- Lot/batch No.: CHPK 10/43-53.
- Expiration date of the lot/batch: 31-May-2005.
- Storage condition of test material: In the original container, at room temperature (range of 20 ± 3 °C), away from direct sunlight.

Test animals

Species:

rat

Strain:

other: HanBrI: Wist

Sex:

female

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Source: RCC Ltd, Laboratory Animal Services CH-4414 Füllinsdorf / Switzerland.
- Age at study initiation: 12 weeks.
- Weight at study initiation: 175.8 to 188.4 g at Day 1 of treatment.
- Fasting period before study: 17 hours.
- Housing: In groups of three in Makrolon type-4 cages with wire mesh tops and standard softwood bedding.
- Diet (e.g. ad libitum): Pelleted standard Provimi Kliba 3433 rat/mouse maintenance diet, batch no. 4/03 (Provimi Kliba AG, CH-4303 Kaiseraugst/Switzerland), ad libitum.
- Water (e.g. ad libitum): Community tap water from Füllinsdorf, ad libitum.
- Acclimation period: Under laboratory conditions, after health examination. Only animals without any visible signs of illness were used for the study. Period was not specified in the study report.



ENVIRONMENTAL CONDITIONS
- Temperature (°C): 22 ± 3.
- Humidity (%): 30-70.
- Air changes (per hr): 10-15.
- Photoperiod (hrs dark / hrs light): 12 / 12.

Administration / exposure

Route of administration:

oral: gavage

Vehicle:

corn oil

Details on oral exposure:

VEHICLE
- Concentration in vehicle: 0.2 g/mL.
- Amount of vehicle (if gavage): 10 mL/kg body weight.
- Justification for choice of vehicle: Corn oil was found to be a suitable vehicle. The vehicle was chosen after a non-GLP solubility trial which was performed before the study initiation date. This trial formulation is excluded from the GLP statement of compliance.

- Lot/batch no. (if required): Batch No. 37255780.


MAXIMUM DOSE VOLUME APPLIED: 10 mL/kg body weight.


DOSAGE PREPARATION (if unusual): The dose formulations were made shortly before each dosing occasion using a magnetic stirrer as homogenizer.
The test item was weighed into a tared glass beaker on a suitable precision balance and the vehicle added (weight:volume).
Homogeneity of the test item in the vehicle was maintained during administration using a magnetic stirrer.

Doses:

2000 mg/kg body weight.

No. of animals per sex per dose:

6 females per dose.

Control animals:

no

Details on study design:

- Duration of observation period following administration: 14 days.
- Frequency of observations and weighing:
Mortality / viability: Daily during acclimatization and twice daily during days 1-15.
Clinical signs: Daily during acclimatization and at approximately 1, 2, 3 and 5 hours after administration on test day 1. Once daily during days 2-15. All abnormalities were recorded.
Body weights: On test days 1 (prior to administration), 8 and 15.
- Necropsy of survivors performed: Yes.
- Other examinations performed: clinical signs, body weight,organ weights, other:
Randomization: Selected by hand at time of delivery. No computer generated randomization program.

Statistics:

No statistical analysis was used.

Results and discussion

Preliminary study:

None.

Effect levels

Sex:

female

Dose descriptor:

LD50

Effect level:

> 2 000 mg/kg bw

Remarks on result:

other: None

Mortality:

One animal was found dead on test day 2. The remaining animals survived until the end of the study period.

Clinical signs:

Slightly ruffled fur was observed in three animals from the 1-hour reading to test day 4. The same animals showed hunched posture from the 3-hour reading to test day 3. Slightly to moderately ruffled fur was noted in the other three animals from the 1 -hour reading to either test day 2, 4 or 5. Hunched posture was noted from either the 1-hour or 2-hour reading to the 5-hour reading or to test day 3. Ventral recumbency was noted in one animal at the 1-hour reading and on test days 2 and 3; whereas, another animal showed the same clinical sign on test day 2 before its death.

Body weight:

One animal showed no body weight gain during the last week of the observation period. The body weight of the other animals was within the range commonly recorded for this strain and age.

Gross pathology:

A stomach distended with gas was observed in the animal found dead at the unscheduled necropsy. No macroscopic findings were recorded in the other animals at scheduled necropsy.

Other findings:

The animals were treated and percentage of mortality observed at 2000 mg/kg was 17%.

Applicant's summary and conclusion

Interpretation of results:

Category 5 based on GHS criteria

Remarks:

Migrated information

Executive summary:

One death and several clinical signs occurred at 2000 mg/kg body weight. GHS states to classify in Category 5.