Registration Dossier

Administrative data

Description of key information

Skin irritation

Irritant, Category 2, Monsanto (1978a)

Mild irritant, Category 3, Monsanto (1978b)

Eye irritation

Irritating to eyes, Category 2, OECD 405, Koch (1985)

Irreversible effects on the eye, Category 1, OECD 405, Bagley (1992)

Category 1 or 2, OECD 492, Kaluzhny (2011)

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:
key study
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
test procedure in accordance with national standard methods with acceptable restrictions
Remarks:
Limited documentation
Qualifier:
according to
Guideline:
other: Primary Skin Irritation Test according to the Federal Hazardous Substances Act (FSHA)
Version / remarks:
not specified
Deviations:
not specified
GLP compliance:
no
Remarks:
Study prior to GLP
Specific details on test material used for the study:
SOURCE OF TEST MATERIAL
- Source and lot/batch No.of test material: Monsanto, Pensacola Plant, Gonzalez FL
- Purity: Not reported
Species:
rabbit
Strain:
New Zealand White
Details on test animals and environmental conditions:
no details provided
Type of coverage:
not specified
Preparation of test site:
other: intact and abraded
Vehicle:
unchanged (no vehicle)
Controls:
not required
Amount / concentration applied:
TEST MATERIAL
- Amount(s) applied (volume or weight with unit): 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

OBSERVATION TIME POINTS
- 4, 24, 48, 72 and 168h

SCORING SYSTEM:
- Method of calculation: Draize score
Irritation parameter:
erythema score
Basis:
mean
Remarks:
of 6 animals
Time point:
other: 24h; 48h; 72h
Score:
2.7
Max. score:
4
Reversibility:
fully reversible within: 7 days
Irritation parameter:
edema score
Basis:
mean
Remarks:
of 6 animals
Time point:
other: 24h; 48h; 72h
Score:
1.7
Max. score:
4
Reversibility:
fully reversible within: 7 days
Irritation parameter:
primary dermal irritation index (PDII)
Basis:
mean
Time point:
other: not applicable
Score:
4.5
Max. score:
8
Reversibility:
fully reversible within: 7 days
Other effects:
- Other adverse local effects: 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

3

3

3

2

3

1

0

0

 3.0  2.0

2

3

3

3

2

3

1

0

0

 3.0  2.0

3

3

3

2

2

2

1

0

0

 2.3  2.0

4

3

2

3

2

3

2

0

0

 3.0  2.0

5

3

2

3

1

2

1

0

0

 2.7  1.3

6

2

1

2

1

3

1

0

0

 2.3  1.0

 

 

Interpretation of results:
Category 2 (irritant) based on GHS criteria
Conclusions:
In this in vivo study on rabbits, the results indicate that the test item is a Skin Irritant (UN GHS: Category 2).
Executive summary:

This dermal irritation study was performed according to the method described in the FHSA (Federal Hazardous Substance Act). Six New Zealand Albino rabbits were dermally exposed to 0.5 mL of the test substance of unknown purity for 24 hours. The test substance was applied to shaved intact and abraded skin using occlusive coverage. Animals were observed for up to 7 days following exposure. The skin was scored at 24, 48, 72 and 168 hours after application. Mean Draize scores (mean of all animals, mean of 24 - 72 hour readings) for the intact skin were 2.7 for erythema (three animals with a score of 3.0, 1 animal with a score of 2.7 and 2 animals with a score of 2.3) and 1.7 (four animals with a score of 2.0, one animal with 1.3 and one with 1.0) for oedema. No irritation was found after 7 days (168 hours) and no injury in depth was found.

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:
key study
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
guideline study with acceptable restrictions
Qualifier:
according to
Guideline:
OECD Guideline 405 (Acute Eye Irritation / Corrosion)
GLP compliance:
yes
Specific details on test material used for the study:
SOURCE OF TEST MATERIAL
- Source and lot/batch No.of test material: Fluka AG, Switzerland
- Purity: 99%
Species:
rabbit
Strain:
other: Albino
Details on test animals or tissues and environmental conditions:
TEST ANIMALS
- Source: Dörröds Djur- och Foderservice, Veberöd (Sweden)
- Housing: Individual housing
- Diet (e.g. ad libitum): A controlled amount of feed (Ewos avelsfoder för kanin, Batch nr 3, Ewos AB, Södertälje, Sweden)
- Water (e.g. ad libitum): ad libitum
- Acclimation period: 1 week

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 20 +/- 3°C- Humidity (%): 50 +/- 20%
- Photoperiod (hrs dark / hrs light): 12/12
Vehicle:
unchanged (no vehicle)
Controls:
not required
Amount / concentration applied:
TEST MATERIAL
- Amount(s) applied (volume or weight with unit): 0.1 mL
Duration of treatment / exposure:
4s, 30s, 24h
Observation period (in vivo):
1h, 24h, 48h, 72 h, 10d and 21d
Number of animals or in vitro replicates:
3
Details on study design:
REMOVAL OF TEST SUBSTANCE
- Washing (if done): Rinsing with water
- Time after start of exposure: 4s, 30s, 24h

SCORING SYSTEM:
- Draize

TOOL USED TO ASSESS SCORE:
- ophthalmoscope, biomicroscope, fluorescein
Irritation parameter:
cornea opacity score
Remarks:
(24h exposure)
Basis:
mean
Remarks:
for each of 3 animals
Time point:
other: 24;48;72h
Score:
1.9
Max. score:
4
Reversibility:
fully reversible within: 10 days
Remarks on result:
other: Mean (24,48; 72h) scores of each animal: animal #1 = 1.7; animal #2 = 2; animal #3 = 2
Irritation parameter:
iris score
Remarks:
(24h exposure)
Basis:
mean
Remarks:
for each of 3 animals
Time point:
other: 24;48;72h
Score:
0
Max. score:
2
Reversibility:
fully reversible within: 10 days
Irritation parameter:
conjunctivae score
Remarks:
(24h exposure)
Basis:
mean
Remarks:
for each of 3 animals
Time point:
other: 24;48;72h
Score:
2.1
Max. score:
4
Reversibility:
fully reversible within: 10 days
Irritation parameter:
chemosis score
Remarks:
(24h exposure)
Basis:
mean
Remarks:
for each of 3 animals
Time point:
other: 24;48;72h
Score:
2.3
Max. score:
4
Reversibility:
fully reversible within: 10 days

As the erythema and oedema scores resulting from the 4-sec-exposure are less relevant for an assessment of the eye irritating property of the substance, the details are not reported here.

Interpretation of results:
Category 2 (irritating to eyes) based on GHS criteria
Conclusions:
In this in vivo study on rabbits, the results indicate that the test item is irritating to the eyes of rabbits.
Executive summary:

In this GLP compliant OECD 405 study, one eye of each of 3 rabbits was treated with 0.1 mL cyclohexanol (purity 99%) for a period of 24h, 30s or 4s. Draize scoring of eye changes were performed at 24h, 48h, 72h after instillation. Regarding the 24 hour application, the mean cornea score (all animals, mean of 24 - 72 hour readings) was 1.9 (one animal with a score of 1.7 and two animals with a score of 2.0), the mean iris score was 0, the mean conjuctivae score was 2.1 (one animal with a score of 2.3 and two animals with 2.0) and the mean chemosis score was 2,3 (one animal with a score of 2,3, one with 2,7 and one with 2.0). Effects were reversible within 10 days in all animals.

Endpoint conclusion
Endpoint conclusion:
adverse effect observed (irritating)

Respiratory irritation

Endpoint conclusion
Endpoint conclusion:
adverse effect observed (irritating)

Additional information

In a well-documented human study (van Thriel et al. 2006), cyclohexanol was observed to have respiratory tract irritating properties from concentrations of 427 ppm (1.77 mg/mL).

Justification for classification or non-classification

Skin Irritation

The substance is classified as Skin Irritant Cat. 2. The available relevant data support the legal classification. The result of the key study triggers a classification with Cat. 2 under Regulation (EC) No 1272/2008, Annex I, whereas the result of a supporting study triggers a classification with Cat. 3. Both studies are of comparable quality. Since an erythema score of >= 2.3 was observed for all animals in the key study, the more stringent classification of Cat. 2 "irritating to skin" is recommended.

Eye Irritation

The harmonised CLP classification of this substance does not contain a classification for eye irritation.

On the basis of the Bagley (1992) study, a classification with Cat. 1 under the Regulation (EC) No. 1272/2008, Annex I, may be warranted. However, in three other studies being adequate for an assessment of classification and labelling, the effects on eyes were shown to be less severe and reversible within 21 days. Thus a classification with Cat. 2 according to Regulation (EC) No. 1272/2008, Annex I, criteria is recommended, based on weight-of-evidence.

Respiratory irritation

The harmonised CLP classification of cyclohexanol includes a classification regarding its irritation potential to the respiratory tract. The legal classification is supported by the findings on respiratory tract irritation described in the available human studies.