Cyclohexylbenzene

Endpoint summary

Description of key information

Skin irritation:   
- mean erythema scores (24, 48, 72h): 2 (for 3 animals)    
- mean oedema scores (24, 48, 72h): 2 (for 2 animals); 2.7 (for 1 animal)
Eye irritation:
- mean cornea scores (24, 48, 72h): 0 (for 3 animals)
- mean iris scores (24, 48, 72h): 0 (for 3 animals)
- mean conjunctivae scores (24, 48, 72h): 0.3 (for 3 animals)
- mean chemosis scores (24, 48, 72h): 0 (for 3 animals)

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:

other: Well documented GLP study according to international guideline.

Qualifier:

according to guideline

Guideline:

OECD Guideline 404 (Acute Dermal Irritation / Corrosion)

Version / remarks:

adopted 17 July 1992

Qualifier:

according to guideline

Guideline:

EU Method B.4 (Acute Toxicity: Dermal Irritation / Corrosion)

GLP compliance:

yes (incl. QA statement)

Species:

rabbit

Strain:

New Zealand White

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Source: David Percival Ltd, Moston, Sandbach, Cheshire, UK
- Age at study initiation: 12-16 weeks
- Weight at study initiation: 2.0-3.5 kg
- Housing: individually in suspended metal cages
- Diet: ad libitum (Certified Rabbit Diet (Code 5322) supplied by PMI Nutritional International, Nottingham, UK)
- Water: ad libitum
- Acclimation period: ≥ 5 days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 17-23°C
- Humidity (%): 30-70%
- Air changes (per hr): ≥ 15 days
- Photoperiod (hrs dark / hrs light): 12/12

Type of coverage:

semiocclusive

Preparation of test site:

clipped

Vehicle:

unchanged (no vehicle)

Controls:

not required

Amount / concentration applied:

TEST MATERIAL
- Amount applied: 0.5 ml

Duration of treatment / exposure:

4 h

Observation period:

14 days

Number of animals:

3

Details on study design:

REMOVAL OF TEST SUBSTANCE
- Washing: by gentle swabbing with cotton wool soaked in 74% industrial methylated spirits

Irritation parameter:

erythema score

Basis:

mean

Time point:

other: 24, 48, 72 h

Score:

2

Reversibility:

fully reversible within: 14 days

Irritation parameter:

edema score

Basis:

mean

Time point:

other: 24, 48, 72 h

Score:

2.2

Reversibility:

fully reversible within: 14 days

Erythema/eschar formation

Reading (hrs)	Individual scores - Rabbit number and sex
	11 Male	118 Male	119 Male
24	2	2	2
48	2	2	2
72	2	2	2
Mean score	2	2	2

Oedema formation

Reading (hrs)	Individual scores - Rabbit number and sex
	11 Male	118 Male	119 Male
24	2	3	2
48	2	3	2
72	2	2	2
	2.0	2.7	2.0

Conclusions:

The test material produced a primary irritation index of 4.2.

Executive summary:

The study was performed to assess the irritancy potential of the test material to the skin of the New Zealand White rabbit.

A single 4 -h, semi-occluded application of the test material to the intact skin of 3 rabbits produced well-defined erythema and slight to moderate oedema. Other skin reactions noted were oedema extending ventrally below treatment site, loss of skin elasticity, severe desquamation, reduced regrowth of fur and crust formation, which prevented evaluation of erythema and oedema. No corrosive effects were noted.

The test material produced a primary irritation index of 4.2.

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:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

other: Well documented GLP study according to international guideline.

Qualifier:

according to guideline

Guideline:

OECD Guideline 405 (Acute Eye Irritation / Corrosion)

Version / remarks:

adopted 24 February 1987

Qualifier:

according to guideline

Guideline:

EU Method B.5 (Acute Toxicity: Eye Irritation / Corrosion)

GLP compliance:

yes (incl. QA statement)

Species:

rabbit

Strain:

New Zealand White

Details on test animals or tissues and environmental conditions:

TEST ANIMALS
- Source: David Percival Ltd, Moston, Sandbach
- Age at study initiation: 12-16 weeks
- Weight at study initiation: 2.0-3.5 kg
- Housing: individually in suspended metal cages
- Diet: ad libitum (LABDIET 5322, PMI Nutrition International, Nottingham, UK)
- Water: ad libitum
- Acclimation period: ≥ 5 days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 17-23°C
- Humidity (%): 30-70
- Air changes (per hr): ≥ 15
- Photoperiod (hrs dark / hrs light): 12/12

Vehicle:

unchanged (no vehicle)

Controls:

not required

Amount / concentration applied:

TEST MATERIAL
- Amount(s) applied: 0.1 mL

Observation period (in vivo):

72 h

Number of animals or in vitro replicates:

3

Details on study design:

SCORING SYSTEM: Draize JH (1977)

TOOL USED TO ASSESS SCORE: hand-slit lamp / biomicroscope / fluorescein

Irritation parameter:

cornea opacity score

Basis:

mean

Time point:

other: 24, 48 and 72 h

Score:

0

Irritation parameter:

iris score

Basis:

mean

Time point:

other: 24, 48 and 72 h

Score:

0

Irritation parameter:

conjunctivae score

Remarks:

(redness)

Basis:

mean

Time point:

other: 24, 48 and 72h

Score:

0.33

Reversibility:

fully reversible within: 48 h

Irritation parameter:

chemosis score

Basis:

mean

Time point:

other: 24, 48 and 72h

Score:

0

Individual scores and individual total scores for ocular irritation.

Rabbit n° and sex	61 Male				155 Male				156 Female
Time after treatm.	1h	24h	48h	72h	1h	24h	48h	72h	1h	24h	48h	72h
Cornea E = Degree of opacity F = Area of cornea	0 0	0 0	0 0	0 0	0 0	0 0	0 0	0 0	0 0	0 0	0 0	0 0
Score (E x F)	0	0	0	0	0	0	0	0	0	0	0	0
Iris D	0	0	0	0	0	0	0	0	0	0	0	0
Score (D x 5)	0	0	0	0	0	0	0	0	0	0	0	0
Conjunctivae A = Redness B = Chemosis C = Discharge	2 1 2	1 0 1	0 0 0	0 0 0	2 1 2	1 0 1	0 0 0	0 0 0	2 1 1	1 0 0	0 0 0	0 0 0
Score (A + B + C) x 2	10	4	0	0	10	4	0	0	8	2	0	0
Total Score	10	4	0	0	10	4	0	0	8	2	0	0

Interpretation of results:

not irritating

Remarks:

Migrated information Criteria used for interpretation of results: EU

Conclusions:

The test material produced an overall average score of 3.3 after 1 h.

Executive summary:

The study was performed to assess the irritancy potential of the test material to the eye of the New Zealand White rabbit.

A single application of the test material to the non-irrigated eye of 3 rabbits produced moderate conjunctival irritation. All treated eyes appeared normal at the 48 h observation. The test material produced an overall average score of 3.3 after 1 h.

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed (not irritating)

Respiratory irritation

Endpoint conclusion

Endpoint conclusion:

no study available

Additional information

One key study is available for skin irritation, and one for eye irritation.

Skin irritation

The key study that is available on skin irritation is a well-documented in vivo study according to OECD 404 (Sanders, 2001 (d)). In this experiment, a single 4 h, semi-occluded application of the test material to the intact skin of three rabbits produced well-defined erythema and slight to moderate oedema. Other skin reactions noted were oedema extending ventrally below treatment site, loss of skin elasticity, severe desquamation, reduced regrowth of fur and crust formation, which prevented evaluation of erythema and oedema. No corrosive effects were noted.

Eye irritation

 

The key study that is available for eye irritation is a well-documented in vivo study according to OECD 405 (Sanders, 2001 (e)). In this experiment, a single application of the test material to the non-irrigated eye of three rabbits produced moderate conjunctival irritation 1h after test substance administration. All treated eyes appeared normal at the 48 h observation.

 

The findings of the available supporting studies for skin and eye irritation are in line with those of the key studies.

Justification for selection of skin irritation / corrosion endpoint:
The study is GLP compliant and has Klimisch score 1.

Justification for selection of eye irritation endpoint:
The study is GLP compliant and has Klimisch score 1.

Effects on skin irritation/corrosion: irritating

Justification for classification or non-classification

The observed skin effects showed a mean (24 - 48 -72h) value of 2.7 in one animal. The mean value for the other two animals is < 2.3, and all effects are fully reversible within 14 days. Therefore, according to the criteria described in section 3.2.2 of EU Regulation n° 1272/2008 on classification, labelling and packaging of substances and mixtures (CLP), the skin irritation scores as determined in the in vivo skin irritation tests do not require a classification as skin corrosive or skin irritant.

According to the criteria described in section 3.2.5 - 3.2.6 of Annex VI to Council Directive 67/548/EEC on the Classification, Packaging and Labelling of Dangerous Substances (DSD), classification as Xi, R38; irritating to the skin is required.

According to the criteria described in section 3.3.2 of EU Regulation n° 1272/2008 on classification, labelling and packaging of substances and mixtures (CLP), the eye irritation scores as determined in the in vivo eye irritation tests do not require a classification as eye irritant.

According to the criteria described in section 3.2.5 - 3.2.6 of Annex VI to Council Directive 67/548/EEC on the Classification, Packaging and Labelling of Dangerous Substances (DSD), the result of the eye irritation test does not require a classification for eye irritant.