Reaction mass of cyclohexanol and cyclohexanone

Endpoint summary

Description of key information

In an acute toxicity study with a mixture of cyclohexanol and cyclohexanone (not further specified) performed similar to the requirements of the OECD guideline study 401 the LD50 was determined with 1120 mg/kg (Monsanto, 1981).

In an acute inhalation hazard test performed with the mixture of cyclohexanol and cyclohexanone (similar to the requirements of the OECD guideline 403) the LC50 was found to be > 6.6 mg/l.

No data on dermal acute toxicity are available.

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:

comparable to guideline study with acceptable restrictions

Qualifier:

equivalent or similar to guideline

Guideline:

OECD Guideline 401 (Acute Oral Toxicity)

Deviations:

yes

Remarks:

no data on substance purity, prior to GLP, limited reporting on study design and methods

GLP compliance:

no

Test type:

standard acute method

Specific details on test material used for the study:

Composition: no data

Species:

rat

Strain:

Sprague-Dawley

Sex:

male/female

Route of administration:

oral: unspecified

Vehicle:

unchanged (no vehicle)

Details on oral exposure:

- MAXIMUM DOSE VOLUME APPLIED: not reported

Doses:

794, 1000, 1260, 1580 mg/kg bw

No. of animals per sex per dose:

5 animals/sex/dose

Control animals:

no

Details on study design:

- Duration of observation period following administration: 14 days
- Frequency of observations and weighing: no data
- Necropsy of survivors performed: yes
- Other examinations performed: clinical signs

Key result

Sex:

male/female

Dose descriptor:

LD50

Effect level:

1 120 mg/kg bw

Based on:

test mat.

95% CL:

1 030 - 1 220

Sex:

male

Dose descriptor:

LD50

Effect level:

1 120 mg/kg bw

Based on:

test mat.

95% CL:

970 - 1 290

Sex:

female

Dose descriptor:

LD50

Effect level:

1 120 mg/kg bw

Based on:

test mat.

95% CL:

1 010 - 1 250

Mortality:

794 mg/kg bw: males 0/5; females 0/5
1000 mg/kg bw: males 2/5; females 1/5
1260 mg/kg bw: males 3/5; females 4/5
1580 mg/kg bw : males 5/5; females 5/5
All deaths occured within 2 days

Clinical signs:

other: Lethargy (lastuing up to 7 days), increasing weakness, ocular discharge, collapse and death

Gross pathology:

Decedents: Hemorrhagic lungs, liver hyperemia, discoloration of liver, kidneys and spleen, and acute gastrointestinal infolammation;
Survivors: Viscera appeard normal

Endpoint conclusion

Endpoint conclusion:

adverse effect observed

Dose descriptor:

LD50

Value:

1 120 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:

comparable to guideline study with acceptable restrictions

Qualifier:

equivalent or similar to guideline

Guideline:

OECD Guideline 403 (Acute Inhalation Toxicity)

Version / remarks:

(Inhalation hazard test)

Deviations:

yes

Remarks:

(only 6 hours of exposure, only 6 animals of one sex)

GLP compliance:

not specified

Test type:

standard acute method

Species:

rat

Strain:

Sprague-Dawley

Sex:

male

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Weight at study initiation: 260 g

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 22
- Humidity (%): 70

Route of administration:

inhalation: vapour

Type of inhalation exposure:

not specified

Vehicle:

other: unchanged (no vehicle)

Details on inhalation exposure:

GENERATION OF TEST ATMOSPHERE / CHAMBER DESCRIPTION
- Exposure chamber volume: 35 l

Duration of exposure:

6 h

Concentrations:

6.6 mg/l

No. of animals per sex per dose:

6 males

Control animals:

no

Sex:

male

Dose descriptor:

LC50

Effect level:

> 6.6 mg/L air

Exp. duration:

6 h

Remarks on result:

other: no mortality occurred

Mortality:

No animals died

Clinical signs:

other: No toxic signs

Body weight:

Day 7: 330 g
Day 14: 390 g

Gross pathology:

Viscera appeared normal

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed

Dose descriptor:

discriminating conc.

Value:

6 600 mg/m³ air

Acute toxicity: via dermal route

Endpoint conclusion

Endpoint conclusion:

no study available

Additional information

Cyclohexanol:

In four acute toxicity studies (comparable to OECD guideline 401) the LD50 ranged from 1400 - 2060 mg/kg bw. In two reliable acute inhalative studies the LC50 was shown to be >3.6 mg/l (saturated atmosphere, 4 hours) and > 5.92 mg/l (saturated atmosphere, 7h). In a third study the LC50 was determined to be >4.3 mg/l.

All these studies suggest that cyclohexanol is of moderate acute toxicity via the oral and inhalative route of exposure.

Regarding the dermal acute toxicity no reliable studies are available for an assessment.

Cyclohexanone:

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 (testing date: 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 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. Theses symptoms were seen until day of sacrifice. These data would not indicate a classification for this exposure route.

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. There is also evidence, that humans metabolize Cyclohexanone in partially different pathways as rats. It appears therefore to be prudent to classify Cyclohexanon also for the dermal exposure route.

Reaction mass of cyclohexanol and cyclohexanone:

In an acute toxicity study with a mixture of cyclohexanol and cyclohexanone (not further specified) performed similar to the requirements of the OECD guideline study 401 the LD50 was determined with 1120 mg/kg (Monsanto, 1981). In an acute inhalation hazard test performed with the mixture of cyclohexanol and cyclohexanone (similar to the requirements of the OECD guideline 403) the LC50 was found to be > 6.6 mg/l. No data on dermal acute toxicity are available.

Justification for classification or non-classification

Cyclohexanol:

Regarding acute oral toxicity the substance is classified with Cat. 4 according to Annex VI of Regulation (EC) No. 1272/2008.

The available relevant data on acute oral toxicity support the legal classification.

For acute inhalative toxicity, cyclohexanol is classified with Cat. 4 according to Annex VI of Regulation (EC) No. 1272/2008.

From the chemical structure and the physical-chemical properties, a ready dermal absorption and, hence, a toxicity of similar order of magnitude as from oral administration can be assumed. Therefore, the substance has also been classified for acute dermal toxicity (Cat.4, H312).

Cyclohexanone:

The test substance is classifed for acute inhalation toxicity with Cat. 4 (H 332) according to Annex VI of Regulation (EC) No. 1272/2008.

Based on the data available, the substance has been classified for acute oral toxicity (Cat.4, H302) according to Regulation (EC) No. 1272/2008

From the chemical structure and the physical-chemical properties, a ready dermal absorption and, hence, a toxicity of similar order of magnitude as from oral administration can be assumed.

Therefore, the substance has also been classified for acute dermal toxicity (Cat.4, H312).

Reaction mass of Cyclohexanol and Cyclohexanone:

Based on the data avaiable, the reaction mass is classified for acute toxicity with Cat.4 for all three routes of exposure (H302, H312, H332).