Octan-2-one

Repeated dose toxicity: dermal

Administrative data

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

Data source

Reference

Reference Type:

publication

Title:

Neurophysiological Studies on Rats

Author:

J. Misumi

Year:

1984

Bibliographic source:

British Journal of Industrial Medicine

Materials and methods

Test guideline

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

Test material

Test material information

Constituent 1

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: 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
- Purity: > 97% v/v

Test animals

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

Administration / exposure

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

Doses / concentrations

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

Examinations

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

Results and discussion

Results of examinations

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

Effect levels

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

Target system / organ toxicity

Critical effects observed:

not specified

Any other information on results incl. tables

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

Applicant's summary and conclusion

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.