Reaction mass of cyclohexanol and cyclohexanone

Endpoint summary

Description of key information

In a primary skin irritation test a mixture of cyclohexanone and cyclohexanol (not further specified) was found to be irritating to the skin (Monsanto 1978).

No irritating properties of the mixture of cyclohexanone and cyclohexanol have been observed in an acute eye irritation test (Monsanto 1981).

Key value for chemical safety assessment

Skin irritation / corrosion

Link to relevant study records

Reference

Endpoint:

skin irritation: in vivo

Type of information:

experimental study

Adequacy of study:

supporting study

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

test procedure in accordance with national standard methods with acceptable restrictions

Principles of method if other than guideline:

Primary Skin Irritation Test

GLP compliance:

not specified

Species:

rabbit

Strain:

other: New Zealand Albino Rabbits

Type of coverage:

other: unspecified patch

Preparation of test site:

other: intact and abraded

Vehicle:

unchanged (no vehicle)

Amount / concentration applied:

0.5 ml

Duration of treatment / exposure:

24 hours

Observation period:

168 hours

Number of animals:

6

Details on study design:

DETAILS OF TEST SITE:
- The test substance was applied to intact and abraded skin areas of the test animals

REMOVAL OF TEST SUBSTANCE
- Washing (if done): not reported
- Time after start of exposure: 24h

SCORING SYSTEM:
Draize score;
Time schedule for scoring of skin changes: immediately after application, after 10 min, 1h, 24h, 48h, 72h, 5 days and after 7 days

Irritation parameter:

erythema score

Basis:

mean

Remarks:

of 6 animals

Time point:

24/48/72 h

Score:

4

Max. score:

4

Reversibility:

fully reversible within: 7 days

Irritation parameter:

edema score

Basis:

mean

Remarks:

of 6 animals

Time point:

24/48/72 h

Score:

4

Max. score:

4

Reversibility:

fully reversible within: 7 days

Irritation parameter:

primary dermal irritation index (PDII)

Basis:

mean

Score:

8

Max. score:

8

Reversibility:

fully reversible within: 7 days

Irritant / corrosive response data:

Defatting Effect - Skin sloughed off in seven to ten days. There was no injury in depth

Hours	24		48		72		168		Mean score (24 - 72 h)
Animal No	Eryth.	Edema	Eryth.	Edema	Eryth.	Edema	Eryth.	Edema	Eryth.	Edema
1	4	4	4	4	4	4	0	0	4	4
2	4	4	4	4	4	4	0	0	4	4
3	4	4	4	4	4	4	0	0	4	4
4	4	4	4	4	4	4	0	0	4	4
5	4	4	4	4	4	4	0	0	4	4
6	4	4	4	4	4	4	0	0	4	4

 

 

Interpretation of results:

Category 2 (irritant) based on GHS criteria

Endpoint conclusion

Endpoint conclusion:

adverse effect observed (irritating)

Eye irritation

Link to relevant study records

Reference

Endpoint:

eye irritation: in vivo

Type of information:

experimental study

Adequacy of study:

supporting study

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

test procedure in accordance with national standard methods with acceptable restrictions

Principles of method if other than guideline:

Acute Eye Irritation Test

GLP compliance:

not specified

Specific details on test material used for the study:

Analytical purity/Composition: no data

Species:

rabbit

Strain:

other: New Zealand Albino Rabbits

Amount / concentration applied:

undiluted
Amount applied: 0.1 ml

Duration of treatment / exposure:

24h

Observation period (in vivo):

168h

Number of animals or in vitro replicates:

6

Details on study design:

SCORING SYSTEM: Draize Score

Irritation parameter:

maximum mean total score (MMTS)

Basis:

mean

Score:

27.9

Max. score:

110

Reversibility:

fully reversible within: 7 days

Irritation parameter:

cornea opacity score

Basis:

mean

Remarks:

(6 animals)

Time point:

24/48/72 h

Score:

0.95

Max. score:

4

Reversibility:

fully reversible within: 7 days

Irritation parameter:

iris score

Basis:

mean

Remarks:

(6 animals)

Time point:

24/48/72 h

Score:

0.7

Max. score:

2

Reversibility:

fully reversible within: 7 days

Irritation parameter:

conjunctivae score

Basis:

mean

Remarks:

(6 animals)

Time point:

24/48/72 h

Score:

2.3

Max. score:

3

Reversibility:

fully reversible within: 7 days

Irritation parameter:

chemosis score

Basis:

mean

Remarks:

(6 animals)

Time point:

24/48/72 h

Score:

0.9

Max. score:

4

Reversibility:

fully reversible within: 7 days

Time following instillation		1	2	3	4	5	6
24 hours	Cornea	2	2	2	2	2	2
	Iris	2	2	2	2	1	2
	Conj. Redness	3	3	3	3	3	3
	Chemosis	4	4	4	4	4	4
48 hours	Cornea	1	1	1	1	1	1
	Iris	1	1	1	1	1	1
	Conj. Redness	2	2	3	2	2	2
	Chemosis	1	1	1	1	1	1
72 hours	Cornea	1	1	1	1	1	1
	Iris	0	1	0	0	0	1
	Conj. Redness	1	2	2	2	1	2
	Chemosis	0	0	0	0	0	0
168 hours	Cornea	0	0	0	0	0	0
	Iris	0	0	0	0	0	0
	Conj. Redness	0	0	0	0	0	0
	Chemosis	0	0	0	0	0	0

 

Interpretation of results:

Category 2 (irritating to eyes) based on GHS criteria

Conclusions:

Classification: irritating

Endpoint conclusion

Endpoint conclusion:

adverse effect observed (irritating)

Respiratory irritation

Endpoint conclusion

Endpoint conclusion:

no study available

Additional information

Cyclohexanol:

From the available animal data, cyclohexanol is considered to be a skin irritant. In two skin irritation studies which were performed according to the method described in the FHSA (six rabbits, 24h-exposure, occlusive dressing), cyclohexanol exhibited slight to moderate erythema and edema which were reversible within 7 days.

In one OECD 405 guideline study the application of cyclohexanol resulted in moderate to severe eye irritating effects. In 1/4 animals corneal opacity was not fully reversible within 21 days (pannus), in another animal an iris score of 1 was reported after 21 days. However, in three reliable eye irritation test performed according to the OECD guideline 405 or the FHSA method cyclohexanol exhibited reversible eye irritating effects.

In a well documented human study the substance was assessed to have respiratory tract irritating properties from concentrations of 427 ppm (1.77 mg/ml)

Cyclohexanone:

An OECD guideline study (404) showed slight to moderate erythema as well as slight edema after an exposure period of 3 hours.

After an exposure period of 1 hour, slight to marked erythema and after 4 hours slight to moderate erythema were observed. In an EpiDerm test in vitro a corrosive potential of the test substance has been observed (BASF, 2003).

An in vitro eye irritation test (HET-CAM) showed serious eye damage (BASF, 2006). This was in concordance with an older BASF in vivo study (1966), where severe irritating eye effects were found.

Reaction mass of cyclohexanol and cyclohexanone:

In a primary skin irritation test a mixture of cyclohexanone and cyclohexanol (not further specified) was found to be irritating to the skin (Monsanto 1981). No irritating properties of the mixture of cyclohexanone and cyclohexanol have been observed in an acute eye irritation test (Monsanto 1981).

Justification for classification or non-classification

Cyclohexanol:

Skin Irritation

According to Annex VI of Regulation (EC) No. 1272/2008 the substance is classified with Cat. 2 for skin irritating properties.

The available relevant data support the legal classification. The result of the key study yields to a GHS classification with Cat. 2. As for all animals in the key study a erythema score of >= 2,3 was observed, the GHS classification with Cat. 2 "irritating to skin" was considered to be warranted.

Eye Irritation

On the basis of the Bagley (1992) study a classification with Cat 1 (CLP) may be warranted.

However, in three other studies being acceptable for an assessment of classification and labeling (studies comparable to OECD guideline 405), the effects on eyes were shown to be less severe and reversible within 21 days. Thus, a classification with Cat. 2 according to CLP criteria is considered to be warranted.

Respiratory irritation

Cyclohexanol is classified with STOT SE cat.3 (H335) according to Annex VI of Regulation (EC) No. 1272/2008 (CLP).

The legal classification is supported by the findings on respiratory tract irritation described in the available human studies.

 

Cyclohexanon:

Based on the data available, cyclohexanone is classified for its irritating properties according to Regulation (EC) No. 1272/2008 (H315, H318 and H 335).

Reaction mass of cyclohexanol and cyclohexanone:

 

The substance consists of cyclohexanone and cyclohexanol (see identification/composition). Cyclohexanone is classified with Eye damage/eye irriation Cat. 1 according to Regulation (EC) No. 1272/2008. Cyclohexanol is classfied with eye damage/eye irritation Cat. 2 according to Regulation (EC) No. 1272/2008. However, there is one study available addressing the eye irritating properties of the mixture itself. The findings of this study would not result in any classification regarding eye irritation. Based on all data available, a classification of the mixture with eye irritation Cat. 2 was regarded to be warranted.

Respiratory tract irritation:

There are no data on the mixture of cyclohexanone and cyclohexanol. However, the mixture is classified with STOT SE cat. 3 (H335) based on the legally binding classification of the individual consituents.