Cyclohexylbenzene

Endpoint summary

Key value for chemical safety assessment

Skin sensitisation

Link to relevant study records

Reference

Endpoint:

skin sensitisation: in vivo (non-LLNA)

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 406 (Skin Sensitisation)

Version / remarks:

adopted 17 July 1992

Qualifier:

according to guideline

Guideline:

EU Method B.6 (Skin Sensitisation)

GLP compliance:

yes (incl. QA statement)

Type of study:

guinea pig maximisation test

Species:

guinea pig

Strain:

Dunkin-Hartley

Sex:

male

Details on test animals and environmental conditions:

TEST ANIMALS
- Source: David Hall Limited, Burton-on-Trent, Staffordshire, UK
- Age at study initiation: approximately 8-12 weeks
- Weight at study initiation: 323-451g
- Housing: singly or in pairs in solid-floor polypropylene cages furnished with woodflakes
- Diet: ad libitum (Certified Guinea Pig Diet (Code 5026) supplied by 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

Route:

intradermal and epicutaneous

Vehicle:

arachis oil

Concentration / amount:

Concentrations as used in the main study:
- Intradermal injections: 5% v/v in arachis oil BP
- Topical induction: 100% (undiluted)
- Topical challenge: 75% v/v in arachis oil BP

Route:

epicutaneous, semiocclusive

Vehicle:

arachis oil

Concentration / amount:

Concentrations as used in the main study:
- Intradermal injections: 5% v/v in arachis oil BP
- Topical induction: 100% (undiluted)
- Topical challenge: 75% v/v in arachis oil BP

Details on study design:

RANGE FINDING TESTS: The concentrations of test material to be used at each stage of the main study were determined by "sighting tests" in which groups of guinea pigs were treated with various concentrations of test material.

Sighting test -- Intradermal induction:
Intradermal injections (0.1 ml/injection site) were made on the clipped shoulder of two guinea pigs, using concentrations of 1% and 5% v/v in arachis oil BP. The degree of erythema at the injection sites was assessed approximately 24, 48, 72 hours and 7 days after injection. The degree of oedema was not evaluated. Any evidence of systemic toxicity was also recorded. The highest concentration that caused only mild to moderate skin irritation, an which was well tolerated systemically, was selected for the intradermal induction stage of the main study.

Sighting test -- Topical induction:
Two guinea pigs (intradermally injected with Freund’s Complete Adjuvant fifteen days earlier) were treated with undiluted test material and 3 preparations of the test material (75%, 50% and 25% v/v in arachis oil BP). Applications were made to the clipped flanks under occlusive dressings for an exposure period of 48 hours. The degree of erythema and oedema was evaluated approx. 1, 24 and 48 hours after dressing removal. The highest concentration producing only mild to moderate dermal irritation was selected for the topical induction stage of the main study.

Sighting test -- Topical challenge:
The undiluted test material and 3 preparations of the test material (75%, 50% and 25% v/v in arachis oil BP) were applied to clipped flanks of two guinea pigs under occlusive dressings for an exposure period of 24 hours. These guinea pigs did not form part of the main study but had been treated identically to the control animals of the main study up to day 14. The degree of erythema and oedema was evaluated approx. 1, 24 and 48 hours after dressing removal. The highest non-irritant concentration of the test material and one lower concentration were selected for the topical challenge of the main study.


MAIN STUDY
A. INDUCTION EXPOSURE
- No. of exposures: 2 (intradermal injection (day 0) and topical application (day 7))
- Exposure period: topical application: 48 h
- Control group: intradermal and topical induction procedure was identical to that used for the test animals except that the test material was omitted
- Site: shoulder region
- Concentrations: intradermal injection: (a) Freund's Complete Adjuvant plus distilled water in the ration 1:1 (b) a 5% v/v formulation of test material in arachis oil BP (c) 5% v/v formulation of test material in 1:1 preparation of Freud's Complete Adjuvant plus distilled water

B. CHALLENGE EXPOSURE
- No. of exposures: 1
- Day(s) of challenge: 21
- Exposure period: 24 h
- Site: right (undiluted) and left (75% v/v in arachis oil BP) flank
- Evaluation (hr after challenge): 24 and 48

Positive control substance(s):

no

Remarks:

No concurrent positive control but summary of historical positive control data was present (1998-2001)

Reading:

1st reading

Hours after challenge:

24

Group:

test chemical

Dose level:

all dose levels

No. with + reactions:

0

Total no. in group:

20

Remarks on result:

other: Reading: 1st reading. . Hours after challenge: 24.0. Group: test group. Dose level: all dose levels. No with. + reactions: 0.0. Total no. in groups: 20.0.

Reading:

2nd reading

Hours after challenge:

48

Group:

test chemical

Dose level:

all dose levels

No. with + reactions:

0

Total no. in group:

20

Remarks on result:

other: Reading: 2nd reading. . Hours after challenge: 48.0. Group: test group. Dose level: all dose levels. No with. + reactions: 0.0. Total no. in groups: 20.0.

Reading:

1st reading

Hours after challenge:

24

Group:

negative control

Dose level:

all dose levels

No. with + reactions:

0

Total no. in group:

10

Remarks on result:

other: Reading: 1st reading. . Hours after challenge: 24.0. Group: negative control. Dose level: all dose levels. No with. + reactions: 0.0. Total no. in groups: 10.0.

Reading:

2nd reading

Hours after challenge:

48

Group:

negative control

Dose level:

all dose levels

No. with + reactions:

0

Total no. in group:

10

Remarks on result:

other: Reading: 2nd reading. . Hours after challenge: 48.0. Group: negative control. Dose level: all dose levels. No with. + reactions: 0.0. Total no. in groups: 10.0.

Interpretation of results:

not sensitising

Remarks:

Migrated information Criteria used for interpretation of results: EU

Conclusions:

Under the conditions of the test, the test material produced a 0% (0/20) sensitisation rate and was classified as a non-sensitiser to guinea pig skin.

Executive summary:

The study was performed to assess the contact sensitisation potential of the test material in the albino guinea pig.

20 test and 10 control animals were used for the study. 2 phases were involved in the main study: an induction of a response by intradermal injection and topical application and a topical challenge of that response.

Under the conditions of the test, the test material produced a 0% (0/20) sensitisation rate and was classified as a non-sensitiser to guinea pig skin.

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed (not sensitising)

Additional information:

The skin sensitization potential in albino guinea pigs was evaluated by the Magnusson and Kligman maximization method (according to OECD TG 406; Sanders 2001f (K1)).

Two phases were involved in the main study: (1) an induction of a response by intradermal injection (5% v/v in arachis oil BP) and topical application (undiluted), (2) a topical challenge (undiluted and 75% v/v in arachis oil BP) of that response.

The test substance produced a 0% (0/20) sensitization rate after 48 h.

Migrated from Short description of key information:
The skin sensitization potential in albino guinea pigs was evaluated by the Magnusson and Kligman maximization method. Since the test substance produced a 0% sensitization rate, the substance is not classified as a skin sensitizer.

Justification for selection of skin sensitisation endpoint:
Well-documented study according to international guideline.

Respiratory sensitisation

Endpoint conclusion

Endpoint conclusion:

no study available

Justification for classification or non-classification

According to the CLP criteria (3.4.2.2.3), a response of at least 30% of the animals in case of an adjuvant test method for skin sensitisation is considered as positive. Since the test substance produced a 0% (0/20) sensitization rate after 48 h, It is therefore concluded that the substance is not classified as a skin sensitizer according to the CLP Regulation.

According to the criteria described in section 3.2.7 of Annex VI to Council Directive 67/548/EEC on the Classification, Packaging and Labelling of Dangerous Substances (DSD), the result of the skin sensitisation test does not require a classification for skin sensitising properties.