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Toxicological information

Repeated dose toxicity: oral

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Administrative data

Endpoint:
short-term repeated dose toxicity: oral
Type of information:
experimental study
Adequacy of study:
key study
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
data from handbook or collection of data
Justification for type of information:
Data is from peer reviewed publication

Data source

Reference
Reference Type:
publication
Title:
Cycloalkanones. 7. Hypocholesterolemic Activity of Aliphatic Compounds Related to 2,8-Dibenzylcyclooctanone
Author:
G. L. Carlson,I. H. Hall, and C. Piantadosi
Year:
1975
Bibliographic source:
Journal of Medicinal Chemistry, 1975, Vol. 18, No. 10 pp 1024-1026

Materials and methods

Test guideline
Qualifier:
according to guideline
Guideline:
other: as mentioned below
Principles of method if other than guideline:
The repeated dose toxicity test was conducted on rats to determine the toxic nature of 2-octanone by oral route of administration
GLP compliance:
no
Limit test:
no

Test material

Constituent 1
Chemical structure
Reference substance name:
Octan-2-one
EC Number:
203-837-1
EC Name:
Octan-2-one
Cas Number:
111-13-7
Molecular formula:
C8H16O
IUPAC Name:
octan-2-one
Details on test material:
- Name of test material: Octan-2-one
- Molecular formula: C8H16O
- Molecular weight: 128.21 g/mol
- Substance type: Organic
- Physical state: Liquid
Specific details on test material used for the study:
- Name of test material: 2-octanone
- IUPAC name: octan-2-one
- Molecular formula: C8H16O
- Molecular weight: 128.2134 g/mol
- Substance type: Organic
- Physical state: Liquid
- Impurities (identity and concentrations): No data available

Test animals

Species:
rat
Strain:
Sprague-Dawley
Details on species / strain selection:
No data
Sex:
male
Details on test animals or test system and environmental conditions:
TEST ANIMALS
- Source: Zivic Miller, Allison Park, Pa.)
- Age at study initiation:No data available
- Weight at study initiation: No data available
- Fasting period before study: No data available
- Housing:
- Diet (e.g. ad libitum): Purina lab chow ad libitum
- Water (e.g. ad libitum): water ad libitum
- Acclimation period: No data available

ENVIRONMENTAL CONDITIONS
- Temperature (°C): No data available
- Humidity (%):No data available
- Air changes (per hr): No data available
- Photoperiod (hrs dark / hrs light): No data available

IN-LIFE DATES: From: To: No data available

Administration / exposure

Route of administration:
oral: gavage
Details on route of administration:
No data
Vehicle:
other: carboxymethylcellulose- H20 (1% CMC) solution
Details on oral exposure:
PREPARATION OF DOSING SOLUTIONS: 2-octanone was suspended in 1% carboxymethylcellulose- H20 (1% CMC) and homogenized at dose level of 0 or 10 mg/Kg/day

DIET PREPARATION
- Rate of preparation of diet (frequency): No data
- Mixing appropriate amounts with (Type of food): No data
- Storage temperature of food: No data

VEHICLE
- Justification for use and choice of vehicle (if other than water): 1% carboxymethylcellulose- H20 (1% CMC)
- Concentration in vehicle: 10 mg/Kg/day
- Amount of vehicle (if gavage): No data
- Lot/batch no. (if required): No data
- Purity: No data
Analytical verification of doses or concentrations:
not specified
Details on analytical verification of doses or concentrations:
No data
Duration of treatment / exposure:
16 days
Frequency of treatment:
Daily at 11:00 am
Doses / concentrations
Remarks:
0 or 10 mg/kg/day
No. of animals per sex per dose:
Total: 16
0 mg/Kg day: 8
10 mg/Kg day: 8
Control animals:
yes, concurrent vehicle
Details on study design:
Controls were given 1%CMC(carboxymethylcellulose-H20)
Positive control:
No data available

Examinations

Observations and examinations performed and frequency:
CAGE SIDE OBSERVATIONS: Not specified
- Time schedule: Not specified
- Cage side observations checked in table [No.?] were included. Not specified

DETAILED CLINICAL OBSERVATIONS: Yes
- Time schedule: Not specified

BODY WEIGHT: Yes
- Time schedule for examinations: Not specified

FOOD CONSUMPTION AND COMPOUND INTAKE (if feeding study): Not specified
- Food consumption for each animal determined and mean daily diet consumption calculated as g food/kg body weight/day: Not specified
- Compound intake calculated as time-weighted averages from the consumption and body weight gain data: Not specified

FOOD EFFICIENCY:
- Body weight gain in kg/food consumption in kg per unit time X 100 calculated as time-weighted averages from the consumption and body weight gain data: Not specified

WATER CONSUMPTION AND COMPOUND INTAKE (if drinking water study): Not specified
- Time schedule for examinations: Not specified

OPHTHALMOSCOPIC EXAMINATION: Not specified
- Time schedule for examinations: Not specified
- Dose groups that were examined: Not specified

HAEMATOLOGY: Not specified
- Time schedule for collection of blood: Not specified
- Anaesthetic used for blood collection: Not specified
- Animals fasted: Not specified
- How many animals: Not specified
- Parameters checked in table [No.?] were examined. Not specified

CLINICAL CHEMISTRY: Yes
- Time schedule for collection of blood: On day 4, 10 and 16 after the last dose (24 hr)
- Animals fasted: Not specified
- How many animals: Not specified
- Parameters checked in table [No.?] were examined. Serum cholesterol level and Hypocholesterolemic Activity was observed

URINALYSIS: Not specified
- Time schedule for collection of urine: Not specified
- Metabolism cages used for collection of urine: Not specified
- Animals fasted: Not specified
- Parameters checked in table [No.?] were examined. Not specified

NEUROBEHAVIOURAL EXAMINATION: Not specified
- Time schedule for examinations: Not specified
- Dose groups that were examined: Not specified
- Battery of functions tested: sensory activity / grip strength / motor activity / other: Not specified

IMMUNOLOGY: Not specified
- Time schedule for examinations: Not specified
- How many animals: Not specified
- Dose groups that were examined: Not specified
- Parameters checked in table [No.?] were examined. Not specified

OTHER: Not specified
Sacrifice and pathology:
No data available
Other examinations:
No data available
Statistics:
The number of animals in a group, expressed as N, the mean of the percent of control, and standard deviation, expressed as x± S.D.,are noted. The probable significant level ( p ) was determined by the Student's t test according to the procedure of Snedecor.

Results and discussion

Results of examinations

Clinical signs:
no effects observed
Mortality:
not specified
Body weight and weight changes:
no effects observed
Food consumption and compound intake (if feeding study):
not specified
Food efficiency:
not specified
Water consumption and compound intake (if drinking water study):
not specified
Ophthalmological findings:
not specified
Haematological findings:
not specified
Clinical biochemistry findings:
effects observed, treatment-related
Urinalysis findings:
not specified
Behaviour (functional findings):
not specified
Immunological findings:
not specified
Organ weight findings including organ / body weight ratios:
not specified
Gross pathological findings:
not specified
Neuropathological findings:
not specified
Histopathological findings: non-neoplastic:
not specified
Histopathological findings: neoplastic:
not specified
Other effects:
not specified
Details on results:
Clinical signs and mortality: No observable toxic effects were noted

Body weight and weight gain: No significant changes in body weight change was observed.

Food consumption and compound intake: No data available

Food efficiency: No data available

Water consumption and compound intake: No data available

Opthalmoscopic examination: No data available

Haematology: No data available

Clinical chemistry: 2-octanone was found to reduce serum choleterol to 34% of control

Urinanalysis No data available

Neurobehaviour: No data available

Organ weights: No data available

Gross pathology: No data available

Histopathology: No data available

Effect levels

Key result
Dose descriptor:
NOAEL
Effect level:
10 mg/kg bw/day (nominal)
Based on:
test mat.
Sex:
male
Basis for effect level:
other: No significant changes were observed at the mentioned dose level

Target system / organ toxicity

Critical effects observed:
not specified

Any other information on results incl. tables

Table I. Hypocholesterolemic Activity of 2-ooctanone at 10 mg/kg/day in Sprague-Dawley Rats

 

Serum cholesterol as % of control on day

% body weight increase

4

10

16

 

Control(1% CMC)

100±7

100±12

100±8

100±4

2-octanone (10 mg/Kg/day)

74±11

59±7

34±8

100±5

Applicant's summary and conclusion

Conclusions:
The no observed adverse effect level (NOAEL) for 2-octanone when administered orally by intubation to male rats was 10 mg/kg/day daily in 16 days study period.

Executive summary:

Subacute toxicity study was performed to determine the toxic nature of 2-octanone upon repeated exposure by oral intubation route. The test compound 2-octanone was administered to male Sprague-Dawley rats daily for 16 days using 0.2cc oral intubation needle. The animals were observed for clinical signs if any, changes in body weight, and after the last dose (24 hr), blood was collected by tail vein bleeding and analyzed for serum cholesterol content. 2-octanone was found to reduce serum choleterol level to 34% of control. No significant changes were were noted in body weight and no observable toxic effects were observed. Hence, the no observed adverse effect level (NOAEL) for 2-octanone when administered orally by intubation to male rats was 10 mg/kg/day daily in 16 days study period.