4-methylcyclohexanone

Repeated dose toxicity: inhalation

Administrative data

Endpoint:

short-term repeated dose toxicity: inhalation

Type of information:

experimental study

Adequacy of study:

supporting study

Reliability:

3 (not reliable)

Rationale for reliability incl. deficiencies:

significant methodological deficiencies

Remarks:

Insufficient information on substance identity and purity.

Data source

Reference

Reference Type:

publication

Title:

Unnamed

Year:

1943

Materials and methods

Test guideline

Qualifier:

no guideline followed

Version / remarks:

The study was conducted before OECD test guidelines and GLP were established.

Principles of method if other than guideline:

Test animals were exposed in metal cages or plywood cages. The test air was mixed with a measured amount of test substance vapour, and was then passed into the top of a cage and was thoroughly distributed in the chamber. The flow rate of air ranged from 300 to 800 liters per minute, resulting in one or two air changes per minute. Animals were exposed whole body for 6 hours per day, 5 days per week during a period of 3 or 10 weeks.

GLP compliance:

no

Limit test:

no

Test material

Test material information

Constituent 1

Reference substance name:

4-methylcyclohexanone

EC Number:

209-665-3

EC Name:

4-methylcyclohexanone

Cas Number:

589-92-4

Molecular formula:

C7H12O

IUPAC Name:

4-methylcyclohexan-1-one

Constituent 2

Reference substance name:

3-methylcyclohexanone

EC Number:

209-710-7

EC Name:

3-methylcyclohexanone

Cas Number:

591-24-2

Molecular formula:

C7H12O

Test material form:

liquid

Details on test material:

- Density: 0.914
- Boiling point: 169-170.5°C
- Refractive index: 1.4458

Test animals

Species:

rabbit

Strain:

not specified

Sex:

not specified

Details on test animals or test system and environmental conditions:

Young, healthy rabbits were used in the tests.

Administration / exposure

Route of administration:

inhalation: vapour

Type of inhalation exposure:

whole body

Vehicle:

clean air

Details on inhalation exposure:

GENERATION OF TEST ATMOSPHERE / CHAMBER DESCRIPTION
- Exposure apparatus: metal or plywood chambers
- Method of holding animals in test chamber: not specified
- Source and rate of air: drawn from an indoor floor
- Method of conditioning air: filtered through a steel filter and passed through an electric precipitator, then passed over a cooling coil and afterwards over a steam reheating coil before entering the tubes leading from a main duct to the individual test chambers; before entering a cage the air was mixed with a measured amount of test substance vapour that was generated by pumping defined amounts of liquid substance into a glass well and the substance was evaporated at the same rate as liquid substance was delivered by the pump.
- Temperature, humidity, pressure in air chamber: 24 °C (22 to 25.5 °C), 45% humidity
- Air flow rate: 350 to 800 L/min
- Air change rate: 1 to 2 per minute
- Treatment of exhaust air: exhaust air was removed by an orifice at the rear of a cage and not re-circulated into a test chamber.

TEST ATMOSPHERE
- Brief description of analytical method used: the test substance in the air was determined colorimetrically by measuring the intensity of pink colour produced by a Zimmerman typ reaction with m-dinitrobenzene.
- Samples taken from breathing zone: no

Analytical verification of doses or concentrations:

yes

Details on analytical verification of doses or concentrations:

Samples of air from the test chamber were drawn by using an evacuated 1L glass bulb that was placed in the cage for 3 minutes. Absolute ethyl alcohol was used to extract the test substance from the air. An aliquot of 10 mL of the alcoholic extract was filled into 25 mL volumetric flask and 1 mL of 1% m-dinitrobenzene in absolut alcohol was added, followed by 10 mL water. The sample was incubated at 60 °C for 15 minutes, then 2 mL of 0.3N aqueous potassium hydroxide were added and the sample incubated at 60 °C for 10 minutes. It was then refrigerated at 4-5 °C for 12 to 18 hours before being diluted to 25 mL with 50% ethyl alcohol. The sample was then compared with a freshly prepared standard in the cell of a wedge photometer at 540 nm.

Duration of treatment / exposure:

3 weeks for two higher doses, 10 weeks for two lower doses
6 hours per day

Frequency of treatment:

5 days per week

Doses / concentrations

Doses / concentrations 1

Dose / conc.:

0.82 mg/L air (nominal)

Doses / concentrations 2

Dose / conc.:

2.31 mg/L air (nominal)

Doses / concentrations 3

Dose / conc.:

5.12 mg/L air (nominal)

Doses / concentrations 4

Dose / conc.:

8.19 mg/L air (nominal)

No. of animals per sex per dose:

4

Control animals:

yes, concurrent no treatment

Examinations

Observations and examinations performed and frequency:

Body weight was determined daily prior to exposure, during the period of exposure and for at least two monther after the exposure period.
Erythrocytes, leucocytes and various types of leucocytes were counted weekly and haemoglobin concentration was measured weekly prior to exposure, during the period of exposure and for at least two monther after the exposure period.

Sacrifice and pathology:

Surviving animals were studied for 2 months after exposure ended. Animals were then sacrificed and a detailed gross and microscopic pathologic examination was done.

Statistics:

None

Results and discussion

Results of examinations

Clinical signs:

effects observed, treatment-related

Description (incidence and severity):

Lethargy, distention of the superficial veins of the ear, and salivation during exposure to the two higher concentrations.

Mortality:

no mortality observed

Body weight and weight changes:

not specified

Description (incidence and severity):

The animals had an increase in body weight during the exposure period. The highest average gain in any group was 1105 g per rabbit.

Ophthalmological findings:

effects observed, treatment-related

Description (incidence and severity):

Signs of conjunctival irritation during exposure to the two higher concentrations.

Haematological findings:

no effects observed

Clinical biochemistry findings:

not examined

Urinalysis findings:

not examined

Behaviour (functional findings):

not examined

Immunological findings:

not examined

Organ weight findings including organ / body weight ratios:

not specified

Gross pathological findings:

not specified

Neuropathological findings:

not examined

Histopathological findings: non-neoplastic:

not examined

Histopathological findings: neoplastic:

not examined

Target system / organ toxicity

Critical effects observed:

no

Lowest effective dose / conc.:

2.31 mg/L air (nominal)

System:

eye

Any other information on results incl. tables

A light form of conjunctival irritation, apparent as reddening, was observed at an exposure concentration of 2.31 mg/L. There was no evidence of adverse effects at the exposure concentration of 0.82 mg/L.