Octan-2-one

Endpoint summary

Description of key information

Repeated dose oral:

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

The study does not conclude higher dose value. Hence it is acceptable to take such low NOAEL .

Repeated dose inhalation:

The No Observed Adverse effect concentration (NOAEC) was considered to be  in a dose range of 80 ppm (80 mg/L) (actual dose 78.6 mg/L or 78600 mg/m3) - 6.6mg/m3 when rodents were  treated with test substance.

Repeated dose dermal:

The No observed adverse effect level (NOAEL) is 400 mg/kg in chronic dermal toxicity study when rats were exposed to  test substance for 21 weeks.

Key value for chemical safety assessment

Toxic effect type:

dose-dependent

Repeated dose toxicity: via oral route - systemic effects

Link to relevant study records

Reference

Endpoint:

short-term repeated dose toxicity: oral

Type of information:

experimental study

Adequacy of study:

weight of evidence

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

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 test substance by oral route of administration

GLP compliance:

not specified

Limit test:

no

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

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

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

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

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.

Clinical signs:

no effects observed

Description (incidence and severity):

No observable toxic effects were noted

Mortality:

not specified

Body weight and weight changes:

no effects observed

Description (incidence and severity):

No significant changes in body weight change was 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

Description (incidence and severity):

Test substance as found to reduce serum choleterol to 34% of control

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

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

Remarks on result:

other: No toxic effect were observed

Critical effects observed:

not specified

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

Conclusions:

The no observed adverse effect level (NOAEL) for test substance 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 test substance upon repeated exposure by oral intubation route. The test substance 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. Test substance 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 test substance when administered orally by intubation to male rats was 10 mg/kg/day daily in 16 days study period.

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed

Dose descriptor:

NOAEL

10 mg/kg bw/day

Study duration:

subacute

Species:

rat

Quality of whole database:

The data is K2 peer reviwed publication

Repeated dose toxicity: inhalation - systemic effects

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed

Dose descriptor:

NOAEC

78 600 mg/m³

Study duration:

subchronic

Species:

rat

Quality of whole database:

Weight of evidence prepared from various publication

Repeated dose toxicity: inhalation - local effects

Endpoint conclusion

Endpoint conclusion:

no study available

Repeated dose toxicity: dermal - systemic effects

Link to relevant study records

Reference

Endpoint:

chronic toxicity: dermal

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

Qualifier:

according to guideline

Guideline:

other: Refer below principle

Principles of method if other than guideline:

The repeated dose dermal toxicity test was conducted on Donryu rats exposed for 21 weeks subcutaneously with dose concentration of 400 mg/kg/day of test substance.

GLP compliance:

no

Limit test:

no

Species:

rat

Strain:

other: Donryu

Details on species / strain selection:

No data

Sex:

male

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Source: No data available
- Age at study initiation: No data available
- Weight at study initiation: 200-300 gm
- Fasting period before study: No data available
- Housing: No data available
- Diet (e.g. ad libitum): Standard pellet diet (Nihon Nosan, MR-3-A) ad libitum
- 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

Type of coverage:

other: Subcutaneous injections

Vehicle:

not specified

Details on exposure:

No data available

Analytical verification of doses or concentrations:

not specified

Details on analytical verification of doses or concentrations:

No data

Duration of treatment / exposure:

21 weeks

Frequency of treatment:

5 days per week for 21 weeks

Remarks:

0 or 400 mg/kg/day

No. of animals per sex per dose:

Total: 37
0 mg/Kg/day: 30
400 mg/Kg/day: 7 male rats

Control animals:

yes, concurrent vehicle

Details on study design:

No data available

Positive control:

No data available

Observations and examinations performed and frequency:

CAGE SIDE OBSERVATIONS: Yes
- Time schedule: Every third day
- Cage side observations checked in table [No.?] were included. No data

DETAILED CLINICAL OBSERVATIONS: Yes
- Time schedule: Every third day

DERMAL IRRITATION (if dermal study): No data
- Time schedule for examinations: No data

BODY WEIGHT: Yes
- Time schedule for examinations: Every third day

FOOD CONSUMPTION: Yes
- Food consumption for each animal determined and mean daily diet consumption calculated as g food/kg body weight/day: 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: No data
- Time schedule for examinations: No data

OPHTHALMOSCOPIC EXAMINATION: No data
- Time schedule for examinations: No data
- Dose groups that were examined: No data

HAEMATOLOGY: No data
- Time schedule for collection of blood: No data
- Anaesthetic used for blood collection: No data
- Animals fasted: No data
- How many animals: No data
- Parameters checked in table [No.?] were examined. No data

CLINICAL CHEMISTRY: No data
- Time schedule for collection of blood: No data
- Animals fasted: No data
- How many animals: No data
- Parameters checked in table [No.?] were examined. No data

URINALYSIS: No data
- Time schedule for collection of urine: No data
- Metabolism cages used for collection of urine: No data
- Animals fasted: No data
- Parameters checked in table [No.?] were examined. No data

NEUROBEHAVIOURAL EXAMINATION: Yes
- Time schedule for examinations: No data
- Dose groups that were examined: 400 mg/kg
- Battery of functions tested: sensory activity / grip strength / motor activity / other: Neurological signs and maximum conductioin velocities of motor and sensory fibres (MCV and SCV)

OTHER: The skin temperature of the tail inguinal regions was measured at the beginning of each measurement

Sacrifice and pathology:

No data

Other examinations:

No data available

Statistics:

Statistical significance of difference between mean values for the treated and control group was tested by student’s t test

Clinical signs:

no effects observed

Dermal irritation:

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

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 :
Clinical signs: No appreciable clinical evidence in parameters like effect on growth, Dullness in movement, Difficulty in walking, paralysis in hind limbs were noted. No salivation was observed in test group.

Mortality: No data available

Dermal Irritation: No data available

Body weight and weight gain: No data available

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: No data available

Urinanalysis No data available

Neurobehaviour: No effect of chemical on nerve conduction velocity and motor distal latency was observed as compared to control

Organ weights: No data available

Gross pathology: No data available

Histopathology: No data available

Dose descriptor:

NOAEL

Effect level:

400 mg/kg bw/day

Based on:

test mat.

Sex:

not specified

Basis for effect level:

other: No signs of clinical or neurophysiological evidence of neuropathy was noted

Remarks on result:

other: No toxic effects were observed

Critical effects observed:

not specified

Table: Neurobehavioral changes noted

	Motor conduction velocity		Sensory conduction velocity			Distal latency
			Whole	proximal	Distal
Control		100	100	100	100	100
2-octanone	100		102	101	103	92

Conclusions:

The No observed adverse effect level (NOAEL) is 400 mg/kg in chronic dermal toxicity study when rats were exposed to test substance for 21 weeks.

Executive summary:

Repeated dose chronic toxicity study was performed to determine the dermal toxic nature of test substance . The test substance in, 200 -300 g weighing male Donryu rats were injected subcutaneously with 0 or 400 mg/Kg/day 2 -octanone 5 days/weeks for 21 weeks. The treated animals were observed for clinical signs, body weight and food intake changes and neurological signs and maximum conduction velocities of motor and sensory fibres (MCV and SCV). Treated animals failed to show any appreciable changes in clinical signs like effect on growth, dullness in movement, difficulty in walking, paralysis in hind limbs. No salivation was observed in test group, and neurophysiological evidence of neuropathy was not observed. Hence, the No observed adverse effect level (NOAEL) is 400 mg/kg in chronic dermal toxicity study when rat were exposed to test substance for 21 weeks.

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed

Dose descriptor:

NOAEL

400 mg/kg bw/day

Study duration:

subchronic

Species:

rat

Quality of whole database:

Data is from K2 peer reviewed publication

Repeated dose toxicity: dermal - local effects

Endpoint conclusion

Endpoint conclusion:

no study available

Additional information

 

Peer reviewed publication of test substance was reviewed to determine the toxic nature of 2 -octanone (IUPAC name: octan-2-one CAS NO: 111-13-7) upon repeated exposure by oral route. The summary is as mentioned below:

Repeated dose toxicity: Oral

Subacute toxicity study was performed to determine the toxic nature of test substance upon repeated exposure by oral intubation route. The test substance 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. Test substance 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 test substance when administered orally by intubation to male rats was 10 mg/kg/day daily in 16 days study period.

The study does not conclude higher dose value. Hence it is acceptable to take such low NOAEL .

 

In a 28 days repeated dose toxicity study, the effect of test chemical was evaluated in male and female Sprague Dawley rats. The test chemical was administered by oral gavage in the concentration of 0, 250, 500 and 1000 mg/kg/ body weight/day. The results showed no effect on mortality, no changes were in food consumption and ophthalmology. Changes were observed in clinical signs like soft stool, nasal discharge, red crust around nostrils, perineum soiled with fecal matter were observed. Significant decreased were observed in water consumption and locomotor activity of female rat in 1000 mg/kg dose group. Bodyweight was increased significantly in male and female rats. Significant increase in MCV, Lymphocyte, Basophils level and significant decrease in WBC, platelet, monocytes, neutrophils and eosinophils were observed in male and female rats. Significant changes were observed in the level of testosterone, sodium, total proteins, total cholesterol, SGOT, SGPT, albumin, Blood urea nitrogen (BUN) and Creatinine when treated with 500 and 1000 mg/kg/day. Significant changes were observed in absolute and relative weight of brain, adrenals, spleen, thymus, epididymides, heart, kidneys, ovaries, uterus and liver in 500 and 1000 mg/kg/day. In addition, minimal to mild gross pathological and histopathological changes were observed in liver, spleen and intestine. However, the biological significance of these findings are not related to test chemical. Therefore, the No Observed Adverse Effect Level (NOAEL) was considered to be 1000 mg/kg/day when Sprague-Dawley rat exposed to test substance orally.

Repeated dose oral toxicity study with reproductive and developmental screening was conducted to investigate the repeated dose toxicity of the test material. The chemical was administered by oral gavage route of exposure to dose groups, each of 13 male and 13 female Crj:CD (SD) strain rats upto forty-three days at dose levels of 0, 100, 300 or 1000 mg/kg/day. A control group of 13 males and 13 females was dosed with vehicle alone (corn oil). As a result, in males, abnormalities in death cases and general conditions were not observed in any treated animal. There was also no change in body weight and food consumption suggesting the effect of test chemical administration. Necropsy, histopathological examination, hematology examination, and blood biochemical examination after repeated administration of 42 times also showed no findings or abnormal values suggesting the effect of test chemical administration. In females, there were no deaths in any test chemical administration group. In addition, no change was observed in general condition, body weight and food intake. Necropsy at 4 days postpartum and histopathological examination also did not show findings suggestive of the effect of test chemical administration. On the reproductive and developmental toxicity, test chemical dose up to 1000 mg / kg did not affect mating rate and conception rate. In addition, changes suggesting the effect of test chemical administration on the pregnancy period, birth rate, labor condition and nursing condition of the mother animals were not observed. No treatment related adverse effects were found in either dose group 0, 100, 300 or 1000 mg/kg/day, though some slight changes were observed in blood biochemistry and histopathology in testes. Thus, on the basis of overall discussion of the study, the 'No Observed Effect Level' (NOEL) for repeated dose toxicity by oral route is to be 1000 mg/kg/day.

Repeated dose inhalation:

In subchronic test, Sprague Dawley male and female rats were exposed to test substance by inhalation in the concentration of 0, 80, 400 and 1000 ppm (0, 80, 400 or 1000 mg/L). Actual exposure concentrations is 0, 78.6, 405.8 or 1022.6 ppm (0, 78.6, 405.8 or 1022.6 mg/L) for 6 hours/day, 7 days/week for 50 days. All adult animals survived to study termination and there were no test substance-related changes in mean terminal body weight. For the 1000 mg/L male group, there was a reduction in food consumption during days 0-7. No effect on survival, body weight and weight gain were observed in treated rats as compared to control. Minimal reductions in activity level were observed in 400 and 1000 mg/L dose group and reduction in food consumption during days 0 -7 in 100 mg/L dose group were observed as compared to control. Mean sperm motility and mean epididymal spermatozoan and testicular spermatid counts were comparable among the groups. No test substance-related gross pathology was observed for adult animals from any group. No exposure-related changes were observed during histological examination of the reproductive organs of any of the test substance-exposed animals. Therefore, the No Observed Adverse effect concentration (NOAEC) was considered to be 80 ppm (80 mg/L) (actual dose 78.6 mg/L or 78600 mg/m3) when Sprague-Dawley male and female rats treated with test substance.

Repeated dose oral toxicity was evaluated for test substance using authoritative database. The study assumed the use of rabbits in a subacute study for 30 days .Opthalmoscopic examinations was observed. Since no significant changes were noted, the No observed adverse effect concentration (NOAEC) for test substance in rabbits is estimated to be 6.6 mg/m3/2H after repeated exposure via inhalation route.

 

Repeated dose toxicity: Dermal

Repeated dose chronic toxicity study was performed to determine the dermal toxic nature of test substance . The test substance in, 200 -300 g weighing male Donryu rats were injected subcutaneously with 0 or 400 mg/Kg/day 2 -octanone 5 days/weeks for 21 weeks. The treated animals were observed for clinical signs, body weight and food intake changes and neurological signs and maximum conduction velocities of motor and sensory fibres (MCV and SCV). Treated animals failed to show any appreciable changes in clinical signs like effect on growth, dullness in movement, difficulty in walking, paralysis in hind limbs. No salivation was observed in test group, and neurophysiological evidence of neuropathy was not observed. Hence, the No observed adverse effect level (NOAEL) is 400 mg/kg in chronic dermal toxicity study when rat were exposed to test substance for 21 weeks.

Repeated dose chronic dermal toxicity study was performed to determine the dermal toxic nature of test substance upon repeated applcatioin by dermal route of exposure. The test chemical was administered subcutaneously in daily dose of 400 mg/kg into the back of seven rats, weighing 290g, 5 days per week for a period of 21 weeks. The animals were observed for clinical signs, changes in body weight and neurophysiological changes. Treated animals failed to exhibit apparent clinical and neurophysiologic evidence except for a slight inhibition of weight gain and narcotic effects after treatment. Hence, the No observed adverse effect level (NOAEL) for test substance in rats exposed for 21 weeks is 400 mg/kg.

Based on the data available from the test chemical, 2 -octanone (IUPAC name: octan-2-one CAS NO: 111-13-7) not likely to exhibit repeated dose oral ,inhalation and dermal toxicity. Hence the test chemical is not likely to classify as per the criteria mentioned in CLP regulation.

 

 

 

Justification for classification or non-classification

Based on the data available from the test chemical, 2 -octanone (IUPAC name: octan-2-one CAS NO: 111-13-7) not likely to exhibit repeated dose oral ,inhalation and dermal toxicity. Hence the test chemical is not likely to classify as per the criteria mentioned in CLP regulation.