Registration Dossier

Administrative data

Description of key information

Skin irritation (OECD 404): not classified
Eye irritation (OECD 405): irritating

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:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
guideline study
Qualifier:
according to
Guideline:
OECD Guideline 404 (Acute Dermal Irritation / Corrosion)
Version / remarks:
adopted in 1981
Deviations:
no
GLP compliance:
no
Remarks:
study performed prior to implementation of GLP
Species:
rabbit
Strain:
Himalayan
Details on test animals and environmental conditions:
TEST ANIMALS
- Weight at study initiation: 2.2-2.5 kg
- Housing: individually
- Diet: K4 Alleindiaet fuer Kaninchen (Ssniff Versuchstier-Diaeten GmbH, Soest, Germany); ad libitum
- Water: tap water; ad libitum
- Acclimation period: 14 days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 20 ± 1
- Humidity (%): 60 ± 5
- Air changes (per hr): 15
- Photoperiod (hrs dark / hrs light): 12/12

IN-LIFE DATES: From: 07 Dec 1982 To: 15 Dec 1982
Type of coverage:
semiocclusive
Preparation of test site:
clipped
Vehicle:
other: paraffin
Controls:
other: not required, untreated sites of the same animal served as control
Amount / concentration applied:
TEST MATERIAL
- Amount(s) applied: 550 mg
A thick paste was prepared by mixing the test material with a few drops of paraffin.

Duration of treatment / exposure:
4 hours
Observation period:
8 days
Reading time points: 1, 24, 48 and 72 hours, 6 and 8 days
Number of animals:
6 (3 males, 3 females)
Details on study design:
TEST SITE
- Area of exposure: approx. 6 cm² (shaved area: 10 cm x 10 cm)
- Type of wrap if used: The test site was covered with a gauze patch. The patch was held in contact with the skin by means of a polyethylene foil for the duration of the exposure period. Finally the animals were wrapped in flexible bandage.

REMOVAL OF TEST SUBSTANCE
- Washing: Residual test material was carefully removed with distilled water.

SCORING SYSTEM: Draize Scoring System
Irritation parameter:
erythema score
Basis:
animal #1
Time point:
24/48/72 h
Score:
0.33
Max. score:
4
Reversibility:
fully reversible within: 72 hours
Irritation parameter:
erythema score
Basis:
animal #2
Time point:
24/48/72 h
Score:
1
Max. score:
4
Reversibility:
fully reversible within: 6 days
Irritation parameter:
erythema score
Basis:
animal #3
Time point:
24/48/72 h
Score:
0
Max. score:
4
Irritation parameter:
erythema score
Basis:
animal #4
Time point:
24/48/72 h
Score:
1
Max. score:
4
Reversibility:
fully reversible within: 8 days
Remarks on result:
other: eschar formation at day 6
Irritation parameter:
erythema score
Basis:
animal #5
Time point:
24/48/72 h
Score:
1.67
Max. score:
4
Reversibility:
fully reversible within: 8 days
Remarks on result:
other: score = 1 at 1 h-reading; eschar formation at day 6
Irritation parameter:
erythema score
Basis:
animal #6
Time point:
24/48/72 h
Score:
2
Max. score:
4
Reversibility:
fully reversible within: 8 days
Remarks on result:
other: eschar formation at day 6
Irritation parameter:
edema score
Basis:
animal #1
Time point:
24/48/72 h
Score:
1
Max. score:
4
Reversibility:
fully reversible within: 6 days
Remarks on result:
other: score = 1 at 1 h-reading
Irritation parameter:
edema score
Basis:
animal #2
Time point:
24/48/72 h
Score:
0.67
Max. score:
4
Reversibility:
fully reversible within: 72 hours
Irritation parameter:
edema score
Basis:
animal #3
Time point:
24/48/72 h
Score:
0
Max. score:
4
Irritation parameter:
edema score
Basis:
animal #4
Time point:
24/48/72 h
Score:
2.33
Max. score:
4
Reversibility:
fully reversible within: 6 days
Remarks on result:
other: score = 2 at 1 h-reading
Irritation parameter:
edema score
Basis:
animal #5
Time point:
24/48/72 h
Score:
1.33
Max. score:
4
Reversibility:
fully reversible within: 72 hours
Remarks on result:
other: score = 2 at 1 h-reading
Irritation parameter:
edema score
Basis:
animal #6
Time point:
24/48/72 h
Score:
0.33
Max. score:
4
Reversibility:
fully reversible within: 48 h
Remarks on result:
other: score = 1 at 1 h-reading
Interpretation of results:
study cannot be used for classification
Remarks:
Migrated information
Conclusions:
Under the conditions of this skin irritation study in the rabbit, the test substance is not considered skin irritating.
Endpoint conclusion
Endpoint conclusion:
no adverse effect observed (not 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
Remarks:
50 mg application amount, no irrigation
Qualifier:
according to
Guideline:
OECD Guideline 405 (Acute Eye Irritation / Corrosion)
Version / remarks:
adopted in 2012
Deviations:
yes
Remarks:
no pretreatment with topical anesthetics and systemic analgesics; 6 animals; 50 mg application amount; no irrigation (no data, if substance was already removed by physiological mechanisms at the first observation time point)
Qualifier:
according to
Guideline:
OECD Guideline 405 (Acute Eye Irritation / Corrosion)
Version / remarks:
adopted in May 1981
Deviations:
no
GLP compliance:
no
Remarks:
study performed prior to implementation of GLP
Species:
rabbit
Strain:
Himalayan
Details on test animals or tissues and environmental conditions:
TEST ANIMALS
- Weight at study initiation: males / females 2.3-2.7 kg
- Housing: individually in stainless steel cages
- Diet: K4 Alleindiaet fuer Kaninchen (Ssniff Versuchstier-Diaeten GmbH, Soest, Germany); ad libitum
- Water: tap water; ad libitum
- Acclimation period: 14 days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 20 ± 1
- Humidity (%): 60 ± 5
- Air changes (per hr): 15
- Photoperiod (hrs dark / hrs light): 12/12

IN-LIFE DATES: From: 21 Dec 1982 To: 29 Dec 1982
Vehicle:
unchanged (no vehicle)
Controls:
other: untreated eye of the same animal served as control
Amount / concentration applied:
TEST MATERIAL
- Amount applied: 50 mg
- Concentration: undiluted
Duration of treatment / exposure:
single application without washing
Observation period (in vivo):
8 days
Reading time points: 1, 24, 48, and 72 hours, 6 and 8 days after treatment
Number of animals or in vitro replicates:
6 (3 males, 3 females)
Details on study design:
SCORING SYSTEM: Draize scoring system

TOOL USED TO ASSESS SCORE: hand-slit lamp / fluorescein (at the 1, 24, 48 and 72 hours, 6 days observation interval)
Irritation parameter:
cornea opacity score
Basis:
animal #1
Time point:
24/48/72 h
Score:
0.67
Max. score:
4
Reversibility:
fully reversible within: 72 hours
Remarks on result:
other: score = 1 at 1 h-reading
Irritation parameter:
cornea opacity score
Basis:
animal #2
Time point:
24/48/72 h
Score:
1
Max. score:
4
Reversibility:
fully reversible within: 8 days
Remarks on result:
other: score = 1 at 1 h-reading
Irritation parameter:
cornea opacity score
Basis:
animal #3
Time point:
24/48/72 h
Score:
0
Max. score:
4
Irritation parameter:
cornea opacity score
Basis:
animal: #4, #5 and #6
Time point:
24/48/72 h
Score:
1
Max. score:
4
Reversibility:
fully reversible within: 6 days
Remarks on result:
other: score = 1 at 1 h-reading
Irritation parameter:
iris score
Basis:
animal #1
Time point:
24/48/72 h
Score:
0.33
Max. score:
2
Reversibility:
fully reversible within: 48 hours
Irritation parameter:
iris score
Basis:
animal #2
Time point:
24/48/72 h
Score:
0.33
Max. score:
2
Reversibility:
fully reversible within: 6 days
Irritation parameter:
iris score
Basis:
animal: #3, #5 and #6
Time point:
24/48/72 h
Score:
0
Max. score:
2
Irritation parameter:
iris score
Basis:
animal #4
Time point:
24/48/72 h
Score:
0.67
Max. score:
2
Reversibility:
fully reversible within: 6 days
Irritation parameter:
conjunctivae score
Basis:
animal: #1 and #6
Time point:
24/48/72 h
Score:
2
Max. score:
3
Reversibility:
fully reversible within: 6 days
Remarks on result:
other: score = 1 at 1 h-reading
Irritation parameter:
conjunctivae score
Basis:
animal #2
Time point:
24/48/72 h
Score:
2.33
Max. score:
3
Reversibility:
fully reversible within: 6 days
Remarks on result:
other: score = 1 at 1 h-reading
Irritation parameter:
conjunctivae score
Basis:
animal #3
Time point:
24/48/72 h
Score:
1
Max. score:
3
Reversibility:
fully reversible within: 72 h
Remarks on result:
other: score = 1 at 1 h-reading
Irritation parameter:
conjunctivae score
Basis:
animal #4
Time point:
24/48/72 h
Score:
2
Max. score:
3
Reversibility:
fully reversible within: 6 days
Remarks on result:
other: score = 1 at 1 h-reading
Irritation parameter:
conjunctivae score
Basis:
animal #5
Time point:
24/48/72 h
Score:
1.33
Max. score:
3
Reversibility:
fully reversible within: 6 days
Remarks on result:
other: score = 1 at 1 h-reading
Irritation parameter:
chemosis score
Basis:
animal: #1, #2, #4 and #6
Time point:
24/48/72 h
Score:
0
Max. score:
4
Reversibility:
fully reversible within: 24 h
Remarks on result:
other: score = 1 at 1 h-reading
Irritation parameter:
chemosis score
Basis:
animal #3
Time point:
24/48/72 h
Score:
0.33
Max. score:
4
Reversibility:
fully reversible within: 72 hours
Remarks on result:
other: score = 1 at 1 h-reading
Irritation parameter:
chemosis score
Basis:
animal #5
Time point:
24/48/72 h
Score:
0
Max. score:
4
Reversibility:
fully reversible within: 24 h
Remarks on result:
other: score = 2 at 1 h-reading
Irritant / corrosive response data:
Conjunctival discharge of grade 1 (any amount different from normal) and grade 2 (discharge with moistening of the lids and hairs just adjacent to lids) was observed in all animals at the 1 h-reading time point. At the 72 h-reading time point discharge was no longer noted except one male rabbit.
Interpretation of results:
Category 2A (irritating to eyes) based on GHS criteria
Remarks:
Migrated information
Conclusions:
Under the conditions of this eye irritation study in the rabbit, the test item caused mean scores following grading at 24, 48 and 72 h after test substance instillation of ≥ 1 for corneal opacity and of ≥ 2 for conjunctival redness in 4 out of 6 tested animals and is therefore considered as irritating to eyes (Category 2, H319) according to Regulation (EC) 1272/2008. The effects were fully reversible within 8 days, at the latest.
Endpoint conclusion
Endpoint conclusion:
adverse effect observed (irritating)

Respiratory irritation

Endpoint conclusion
Endpoint conclusion:
no study available

Additional information

Skin

The skin irritation potential of 4-tert-butylcyclohexanol has been investigated in three studies in rabbits and in one closed patch test in humans.

A study investigating the skin irritation potential of 4-tert-butylcyclohexanol was performed in Himalayan rabbits according to OECD Guideline 404 adopted in 1981 (82-0310-DKT). 0.55 g of a thicky paste of the test substance, which was prepared my mixing the test substance with a few drops of paraffin, was applied to the intact skin of 3 male and 3 female animals under semi-occlusive conditions for 4 h. Slight erythema (mean scores over 24, 48 and 72 h: 0.33, 1, 0, 1, 1.67 and 2) and slight edema (mean scores over 24, 48 and 72 h: 1, 0.67, 0, 2.33, 1.33 and 0.33) were observed. The effects were fully reversible within 6 days and eschar formation present in 3/6 animals at day 6 was no longer observed on day 8. Under the conditions of this guideline study 4-tert-butylcyclohexanol is considered not to be irritating to skin.

In a further skin irritation study in rabbits, slight to obvious primary irritation was noted after application of the test substance in a concentration of 80% in water for durations of 1 min up to 20 h (BASF, 1975). However, these results were inconclusive for risk assessment, since no evaluation of skin irritation according to the Draize scoring system at 24, 48 and 72 h post-application was performed.

Additional information on skin irritation was provided by Opdyke (1974). 4-tert-Butylcyclohexanol was not irritating when applied to intact and abraded rabbit skin under occlusive conditions for 24 h.

Moreover, no irritation was noted after a 48 h closed patch test with 4% test substance in petrolatum on human subjects (Opdyke, 1974).

In conclusion, 4-tert-butylcyclohexanol is considered not to be irritating to skin.

 

Eye

The eye irritation potential of 4-tert-butylcyclohexanol has been investigated in two in vivo studies.

In the first study, the eye irritation potential of the test substance was determined in a study performed according to the OECD Guideline 405 adopted in 1981 (82-0312-DKT). A single application of 50 mg of the undiluted test substance was applied in the conjunctival sac of one eye of 6 Himalayan rabbits (3 animals per sex). The other eye remained untreated and served as control. Examination and scoring of effects on the eyes were performed at intervals of 1, 24, 48, 72 h and 6 and 8 days after test substance application. The treated eyes were not rinsed. Mean scores over 24, 48 and 72 h after application for corneal opacity were 1 in 4 animals and 0.67 and 0 in one animal each, respectively. Iris mean scores were 0.33 in 2 animals, 0 in 3 animals and 0.67 in one further animal. Conjunctival redness achieved mean scores of 2 in 3 animals and 2.33, 1.33 and 0 in one animal each, respectively. The mean scores for conjunctival swelling (chemosis) after 24, 48 and 72 h were scored 0 for 5 animals and 0.33 for one animal. Discharge was noted in all animals at the 1 h reading and declined continuously in degree and in the number of animals. At the 72 h-reading time point discharge was no longer noted except one male rabbit. All effects were reversible within 6 days, except corneal opacity in one animal being reversible within 8 days. Since, the test substance produced mean score values of ≥ 1 for corneal opacity and of ≥ 2 for conjuctival redness, respectively) in 4 out of 6 animals 4-tert-butylcyclohexanol meets the classification criteria for irritating to eyes according to Regulation (EC) 1272/2008 (Category 2, H319).

In a further eye irritation study, rabbits received a single application of 50 mg undiluted test substance (BASF, 1975). Inflammation processes and scars were noted on the mucous membranes of rabbits' eyes after instillation. However, these results were inconclusive for risk assessment, since no evaluation of eye irritation according to the Draize scoring system at 24, 48 and 72 h post-application was performed.

In conclusion, 4-tert-butylcyclohexanol is considered eye irritating.


Justification for selection of skin irritation / corrosion endpoint:
The selected study is the most adequate and reliable study based on overall quality assessment.

Justification for selection of eye irritation endpoint:
The selected study is the most adequate and reliable study based on overall quality assessment.

Effects on eye irritation: irritating

Justification for classification or non-classification

Skin

The available data on skin irritation / corrosion of the test substance do not meet the criteria for classification according to Regulation (EC) 1272/2008 or Directive 67/548/EEC, and are therefore conclusive but not sufficient for classification.

Eye

The available data on eye irritation of the test substance meet the criteria for classification as Eye Irrit. Category 2 (H319) according to Regulation (EC) 1272/2008. The available data on eye irritation of the test substance do not meet the criteria for classification according to Directive 67/548/EEC.