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Toxicological information

Repeated dose toxicity: dermal

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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

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: 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.