4-tert-butylcyclohexanone

Acute Toxicity: oral

Administrative data

Endpoint:

acute toxicity: oral

Type of information:

experimental study

Adequacy of study:

key study

Study period:

28 Mar - 02 May 2012

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

other: GLP-Guideline Study

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

2012

Report date:

2012

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:

adopted: 17 December 2001

Deviations:

no

Test guideline 2

Qualifier:

according to guideline

Guideline:

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

Deviations:

no

GLP compliance:

yes (incl. QA statement)

Remarks:

Ministerium für Arbeit, Gesundheit und Soziales des Landes Nordrhein-Westfalen, Düsseldorf, Germany

Test type:

acute toxic class method

Limit test:

no

Test material

Test material information

Constituent 1

Reference substance name:

4-tert-butylcyclohexanone

EC Number:

202-678-5

EC Name:

4-tert-butylcyclohexanone

Cas Number:

98-53-3

Molecular formula:

C10H18O

IUPAC Name:

4-tert-butylcyclohexan-1-one

Details on test material:

- Name of test material (as cited in study report): 4-tert-Butycycloheanone
- Physical state: colourless solid
- Analytical purity: 99.58%
- Lot/batch No.: CHHDKP1901
- Expiration date of the lot/batch: 18 Jan 2014
- Storage condition of test material: room temperature

Test animals

Species:

rat

Strain:

Wistar

Sex:

female

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Source: Harlan GmbH, Horst, Germany
- Age at study initiation: 8 – 12 weeks (females)
- Weight at study initiation: 151 – 186 g (females)
- Fasting period before study: food was withdrawn from the animals between approximately 16 – 24 h before administration and 2 - 4 h after administration of the test substance.
- Housing: the animals were group caged conventionally in polycarbonate cages on low dust wood granulate bedding. Wooden blocks for the environmental enrichment were added to each cage.
- Diet: standard diet “ssniff R/N-H 10 mm (Ratten-/Mäuse-Haltungsf.) V1534-0, ssniff Spezialdiäten GmbH, 59494 Soest“, ad libitum (except during the fasting period)
- Water: tap water, ad libitum
- Acclimation period: at least 5 days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 22 ± 2
- Humidity (%): 55 ± 5
- Air changes (per hr): approximately 10
- Photoperiod (hrs dark / hrs light): 12/12

Administration / exposure

Route of administration:

oral: gavage

Vehicle:

polyethylene glycol

Details on oral exposure:

MAXIMUM DOSE VOLUME APPLIED: 10 mL/kg bw

DOSAGE PREPARATION:
The test item was formulated in polyethylene glycol 400 to give a solution and the applied formulations were well mixed before administration. The test substance was heated to approximately 60 °C for formulation.

CLASS METHOD (if applicable)
- Rationale for the selection of the starting dose: the dose level to be used as the starting dose was selected from one of four fixed levels: 5, 50, 300, and 2000 mg/kg bw. The starting dose level was supposed to be the one that was most likely to produce mortality in some of the dosed animals.

Doses:

300 and 2000 mg/kg bw

No. of animals per sex per dose:

3 (females)

Control animals:

other: not required

Details on study design:

- Duration of observation period following administration: 14 days
- Frequency of observations and weighing: clinical signs and mortality rates were determined several times on the day of administration and subsequently at least once daily during the observation period. The weight gain of the animals was checked weekly until the end of the study.
- Necropsy of survivors performed: yes
- Other examinations performed: clinical signs, body weight,organ weights, grosspathology

Results and discussion

Effect levels

Sex:

female

Dose descriptor:

LD50

Effect level:

> 300 - <= 2 000 mg/kg bw

Based on:

test mat.

Remarks on result:

other: Cut-off of the test substance in 1000 mg/kg bw

Mortality:

300 mg/kg bw: 1/3 female died
2000 mg/kg bw: 2/3 female died

Clinical signs:

other: 300 mg/kg bw: lateral position, clonical clamps, tremor, labored breathing and decreased motility 2000 mg/kg bw: decreased motility, abdominal position, spasmodic state, temporary tremor, narrowed palpebral fissure, tonical cramps, lateral position and la

Gross pathology:

300 and 2000 mg/kg bw: Necropsy and histopathological examination revealed no substance-related findings.
- animals found dead: black discoloured liver and spleen and hemorrhagic lung. For details refer to Table 1 under "any other information on results"

Applicant's summary and conclusion

Interpretation of results:

harmful

Remarks:

Migrated information Criteria used for interpretation of results: EU

Conclusions:

CLP: Acute Oral 4, H302
DSD: Xn, R22