Cyclohexanone

Endpoint summary

Description of key information

The approx. LD50 for acute oral toxicity in the rat is between 1890 (test with 2 - 50% aqueous emulsion with traganth) and 2650 mg/kg (test with solution in olive oil). Clinical signs were prone and lateral position and narcosis. Pathology showed no abnormal findings. This test was carried out according to BASF-internal standards (BASF SE 1966; no data about sex of the animals are available).

Smyth et al. (1969) found an acute oral LD50 value of 1620 mg/kg for male rats (gastric intubation). No data are given for mortalities in single dose groups, clinical signs or gross pathology. All other data/studies available for this route of exposure showed LD50 values near or slightly below 2000 mg/kg.

An LC50 value of > 6.2 mg/l/4 hours for both sexes (rat) was found in an acute inhalation study (BASF-internal standards). No mortalities were seen. Clinical signs were watery eye and nose secretion, mouth smearing, intermittent and accelerated breathing, apathetic, narcosis, scrubby fur. These symptoms were seen until day of sacrifice. These data would not indicate a classification for this exposure route. Cyclohexanone is classified as harmful if inhaled (H332) according to annex VI of Regulation (EC) No. 1272/2008 (CLP). This classification is supported by the studies of Union Carbide (1967) and Gupta et al. (1979), with the limitation that the study by Union Carbide contains only sparse information and the study by Gupta et al. used mice in their experiments and the setting of the experiments were not according to an OECD guideline for the determination of an LC50 value.

No available data have been obtained for the dermal exposure route according to present testing guidelines (semiocclusive; 4 hrs exposure time). From the chemical structure and the physical-chemical properties, however, a ready dermal absorption and, hence, a toxicity of similar order of magnitude as from oral administration can be assumed. It appears therefore to be prudent to classify Cyclohexanone also for the dermal exposure route. This classification is supported by the findings of the Industrial BioTest Labs study (1975). However, it has to be noted that studies conducted at this lab are of questionable reliability, as the FDA discovered several discrepancies between raw data and study reports for studies conducted by this lab.

Key value for chemical safety assessment

Acute toxicity: via oral route

Link to relevant study records

Reference

Endpoint:

acute toxicity: oral

Type of information:

experimental study

Adequacy of study:

key study

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

study well documented, meets generally accepted scientific principles, acceptable for assessment

Qualifier:

no guideline followed

Principles of method if other than guideline:

BASF-internal standards; estimation of the approximative LD50

GLP compliance:

no

Test type:

standard acute method

Limit test:

no

Species:

rat

Strain:

not specified

Sex:

not specified

Details on test animals or test system and environmental conditions:

no data

Route of administration:

oral: gavage

Vehicle:

other: aqueous emulsion resp. solution in olive oil

Details on oral exposure:

no information

Doses:

Test substance given as a 2 - 50% aqueous emulsion with traganth resp. solution in olive oil.

No. of animals per sex per dose:

no data

Control animals:

not specified

Details on study design:

Test substance given as a 2 - 50% aqueous emulsion with traganth resp. solution in olive oil.
Observation period: 7 days

Statistics:

no data

Dose descriptor:

approximate LD50

Effect level:

1 890 mg/kg bw

Remarks on result:

other: test with 2 - 50% aqueous emulsion with traganth

Dose descriptor:

approximate LD50

Effect level:

2 650 mg/kg bw

Remarks on result:

other: test with solution in olive oil

Mortality:

no data

Clinical signs:

other: Prone and lateral position, narcosis

Gross pathology:

Nothing abnormal detected.

Interpretation of results:

other: harmful

Endpoint conclusion

Endpoint conclusion:

adverse effect observed

Dose descriptor:

LD50

Value:

1 890 mg/kg bw

Acute toxicity: via inhalation route

Link to relevant study records

Reference

Endpoint:

acute toxicity: inhalation

Type of information:

experimental study

Adequacy of study:

key study

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

study well documented, meets generally accepted scientific principles, acceptable for assessment

Principles of method if other than guideline:

BASF-internal standards; estimation of the LC50 value

GLP compliance:

no

Test type:

acute toxic class method

Limit test:

yes

Specific details on test material used for the study:

purity: 99.9%

Species:

rat

Strain:

Sprague-Dawley

Sex:

male/female

Details on test animals or test system and environmental conditions:

Body weight range of the animals: 185 ± 15 g
The animals were offered Herilan MRH of H. EGGERSMANN KG, Rinteln/Weser, and tap water ad libitum during the post-exposure observation period.
The animals were kept in fully air-conditioned rooms (temperature 22 ± 2°C and humidity 55 ± 5%) with a day/night rhythm of 12 hours.

Route of administration:

inhalation: vapour

Type of inhalation exposure:

whole body

Details on inhalation exposure:

A concentration estimated on the basis of the data from the inhalation hazard test was used as a first orientating concentration. One concentration allows a no effect level to be established (0 lethality).

Duration of exposure:

4 h

Concentrations:

6.2 mg/l

No. of animals per sex per dose:

10

Control animals:

yes

Details on study design:

The body weight of the animals was checked before the beginning of the test, after 7 days and at the end of the observation period. Clinical findings and lethality were recorded daily.
At the end of the 14-day observation period, the animals were sacrificed with CO2 and were subjected to a gross-pathological examination like all other animals which had died before.

Statistics:

Statistical evaluation of the test were done according to the binomal test (BASF SE).

Sex:

male/female

Dose descriptor:

LC50

Effect level:

> 6.2 mg/L air

Exp. duration:

4 h

Remarks on result:

other: significance level: 1%

Mortality:

none

Clinical signs:

other: Watery eye and nose secretion, mouth smearing, intermittent and accelerated breathing, apathetic, narcosis, scrubby fur. Three of 10 female animals showed alopecia. Symptoms were seen until day of killing.

Body weight:

No significant differences to the control group.

Gross pathology:

Sacrificed animals: nothing abnormal detected.

1) LC50 (4 h) for male and female animals: = > 6.2 mg/l air

2) LC50 (1 h) for male and female animals: = > 25 mg/l air*

3) LC50 (4 h) for male animals: = > 6.2 mg/l air

4) LC50 (1 h) for male animals: = > 25 mg/l air*

5) LC50 (4 h) for female animals: = > 6.2 mg/l air 6) LC50 (1 h) for female animals: = > 25 mg/l air*

* By means of converting the values of the 4-hour LC50 according to the rule of Haber C x t = k

Interpretation of results:

other: The test substance is labelled with R20 (Directive 67/548/EEC)

Endpoint conclusion

Endpoint conclusion:

adverse effect observed

Dose descriptor:

discriminating conc.

Value:

6 200 mg/m³ air

Acute toxicity: via dermal route

Endpoint conclusion

Endpoint conclusion:

no study available