6-chlorohexan-2-one

Repeated dose toxicity: other routes

Administrative data

Endpoint:

short-term repeated dose toxicity: other route

Type of information:

experimental study

Adequacy of study:

key study

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

other: Data is from peer reviewed journal

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 per below mentioned

Principles of method if other than guideline:

The repeated dose toxicity test was conducted on chemical 2-octanone exposed to CF1 mice intraperitonially daily with dose concentration of 50 mg/kg/day.

GLP compliance:

no

Test material

Test material information

Constituent 1

Reference substance name:

111-13-6

IUPAC Name:

111-13-6

Constituent 2

Reference substance name:

Octan-2-one

EC Number:

203-837-1

EC Name:

Octan-2-one

Cas Number:

111-13-7

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

Test animals

Species:

mouse

Strain:

CF-1

Sex:

female

Details on test animals or test system and environmental conditions:

Details on test animal
TEST ANIMALS
- Source: Carworth Farms
- Age at study initiation: No data available
- Weight at study initiation: No data available

- Fasting period before study:
- Housing: No data available
- Diet (e.g. ad libitum): ): Purina lab chow
- Water (e.g. ad libitum): 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:

intraperitoneal

Vehicle:

other: 1% carboxymethylcellulose- H20(CMC)

Details on exposure:

PREPARATION OF DOSING SOLUTIONS:
Test compound was suspended in 1% carboxymethylcellulose- H20 (1% CMC) and homogenized. Doses (mg/kg) were calculated on daily weights of the mice

VEHICLE
- Justification for use and choice of vehicle (if other than water):No data available
- Concentration in vehicle:50 mg/kg/day
- Amount of vehicle (if gavage):1%

Analytical verification of doses or concentrations:

not specified

Duration of treatment / exposure:

19.4 days

Frequency of treatment:

Daily

Doses / concentrations

Remarks:

Doses / Concentrations:
10 mg/kg/day

No. of animals per sex per dose:

No data available

Control animals:

other: Control animals were given 1% carboxymethylcellulose- H20 (CMC) only

Details on study design:

No data available

Examinations

Observations and examinations performed and frequency:

Observations and examinations performed & frequency
CAGE SIDE OBSERVATIONS: No data

DETAILED CLINICAL OBSERVATIONS: No data
-

BODY WEIGHT: No data

FOOD CONSUMPTION AND COMPOUND INTAKE (if feeding study):
- Food consumption for each animal determined and mean daily diet consumption calculated as g food/kg body weight/day: No data
- Compound intake calculated as time-weighted averages from the consumption and body weight gain data: No data

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: No data

WATER CONSUMPTION AND COMPOUND INTAKE (if drinking water study): No data

OPHTHALMOSCOPIC EXAMINATION: No data

HAEMATOLOGY: No data

URINALYSIS: No data

NEUROBEHAVIOURAL EXAMINATION: No data

OTHER: The percent pregnant, the number of viable fetuses per litter, and the number of reabsorption sites and dead in utero per litter were noted and expressed as a percent of the control value.

Sacrifice and pathology:

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 i f S.D.,ar e 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:

not specified

Mortality:

not specified

Body weight and weight changes:

not specified

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:

not specified

Urinalysis findings:

not specified

Behaviour (functional findings):

not specified

Organ weight findings including organ / body weight ratios:

not specified

Gross pathological findings:

not specified

Histopathological findings: non-neoplastic:

not specified

Histopathological findings: neoplastic:

not specified

Details on results:

no antifertility activity was observed at an effective dose level.
The lowered pregnancy rate was observed to 75% of control.

% pregnant %av.no. of fetuses per litter %av no.reabsorption sites per litter
Control 100 100±25 100±25
2-octanone 75 87 0

Effect levels

Dose descriptor:

NOAEL

Effect level:

50 mg/kg bw/day

Based on:

test mat.

Sex:

female

Basis for effect level:

other: Average number of fetuses for CF1,average number of reabsorption sites per litter and lowered pregnancy level.

Target system / organ toxicity

Critical effects observed:

not specified

Applicant's summary and conclusion

Conclusions:

The no observed adverse effect level(NOAEL) was found to be 50 mg/kg/day in repeated dose toxicity study when exposed to female mice intraperitonially.

Executive summary:

Subacute toxicity test has been performed on female CF1 female mice.The test chemical was dosed intraperitonially with test concentration of 50 mg/kg /day in 1% carboxymethylcellulose- H20 as a vechicle daily for 19.4 days as gestation . The percent pregnant, the number ofviable fetuses per litter, and the number of reabsorption sites and dead in utero per litter were noted and expressed as a percent of the control value. In our animal quarters, the average gestation time for rodents was 19.4 days with some seasonal variation. The average number of fetuses and reabsorption sites including uterine death for CFI mice was 12 f 3 and 0.48 f 0.12 per litter, respectively. These values were used to calculate the percent of control values for the test compounds. A change greater than 25% is considered to be significant at the level of p = 0.051.test chemical lowered pregnancy level to 75% of control.The no observed adverse effect level(NOAEL) was found to be 50 mg/kg/day in repeated dose toxicity study when exposed to female mice intraperitonially.