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Skin sensitisation

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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other: GLP compliant, guideline study, available as unpublished report, no restrictions, fully adequate for assessment
Qualifier:
equivalent or similar to guideline
Guideline:
EU Method B.6 (Skin Sensitisation)
GLP compliance:
yes (incl. QA statement)
Type of study:
Buehler test
Justification for non-LLNA method:
Acceptable study that followed sound scientific principles.
Species:
guinea pig
Strain:
Hartley
Sex:
male/female
Details on test animals and environmental conditions:
TEST ANIMALS
- Source: Davidson mill Breeding Labs., Jamesburg, NJ 08831, USA.
- Age at study initiation: Young adult
- Weight at study initiation: Males 344-407 g; Females 314-394 g
- Housing: Individually in stainless steel cages with elevated wire mesh flooring.
- Diet: Purina Guinea Pig diet #5025 ad libitum
- Water: Tap water ad libitum
- Acclimation period: At least 7 days

ENVIRONMENTAL CONDITIONS
- Temperature: 19-27°C
- Humidity: 20-70%
- Photoperiod: 12hrs dark / 12hrs light

IN-LIFE DATES: From: 12 March 1996 To: 12 April 1996
Route:
epicutaneous, occlusive
Vehicle:
other: ethanol (induction applications), acetone (challenge application)
Concentration / amount:
10% (induction and challenge applications)
Route:
epicutaneous, occlusive
Vehicle:
other: ethanol (induction applications), acetone (challenge application)
Concentration / amount:
10% (induction and challenge applications)
No. of animals per dose:
20 (test group), 10 (vehicle control, naive control, positive control and positive control naive groups)
Details on study design:
RANGE FINDING TESTS: Three groups of 4 unexposed animals (2/sex/group) exposed to 25, 20, 15, 10 and 5% in 95% ethyl alcohol once/week for up to 3 weeks to determine the minimally irritating concentration to be used for induction. Two groups of 4 unexposed animals (2/sex/group) exposed to 20, 15, 10 and 5% in acetone once to determine the highest non-irritating concentration to use for challenge.

MAIN STUDY
A. INDUCTION EXPOSURE
- No. of exposures: 3
- Exposure period: 6 h
- Test groups: 20 (9 male and 11 females)
- Control group: 10 (5 male and 5 female)
- Site: left flank
- Frequency of applications: weekly
- Duration: 6 hours
- Concentrations: 10% (test group) vehicle only (control group)
B. CHALLENGE EXPOSURE
- No. of exposures: 1
- Day(s) of challenge: Approximately 15 days after final induction application
- Exposure period: 6 h
- Site: right flank
- Concentrations: 10% (test and control groups)
- Evaluation (hr after challenge): Approximately 24 and 48 h

METHOD OF APPLICATION: Test substance and or vehicle was applied to closely clipped skin using 25mm Hilltop Chambers which was placed on occlusive dental dam (ca 2" x 2") and then placed onto test site. Plastic was then wrapped snugly around the trunk of the animal and overwrapped with elastic tape. After removal of the dressings and Hilltop chamber, the application site was wiped with ethanol, followed by deionised water.
Positive control substance(s):
yes
Remarks:
1-chloro-2,4-dinitrobenzene (DNCB). Induction 0.1% w/v in 50% ethanol:0.9% saline, challenge 0.07% in acetone
Positive control results:
24 and 48 h after challenge very faint redness to moderate redness present. No redness in naive controls. Incidence of sensitisation 8/10 (positive controls), 0/10 (naive controls). Sensitivity of test procedure confirmed.
Reading:
1st reading
Hours after challenge:
24
Group:
test chemical
Dose level:
10%
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: 10%. No with. + reactions: 0.0. Total no. in groups: 20.0.
Reading:
2nd reading
Hours after challenge:
48
Group:
test chemical
Dose level:
10%
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: 10%. No with. + reactions: 0.0. Total no. in groups: 20.0.
Reading:
1st reading
Hours after challenge:
24
Group:
negative control
Dose level:
10%
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: 10%. No with. + reactions: 0.0. Total no. in groups: 10.0.
Reading:
2nd reading
Hours after challenge:
48
Group:
negative control
Dose level:
10%
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: 10%. No with. + reactions: 0.0. Total no. in groups: 10.0.
Reading:
1st reading
Hours after challenge:
24
Group:
other: main test naive control
Dose level:
10%
No. with + reactions:
0
Total no. in group:
10
Remarks on result:
other: Reading: 1st reading. . Hours after challenge: 24.0. Group: other: main test naive control. Dose level: 10%. No with. + reactions: 0.0. Total no. in groups: 10.0.
Reading:
2nd reading
Hours after challenge:
48
Group:
other: main test naive control
Dose level:
10%
No. with + reactions:
0
Total no. in group:
10
Remarks on result:
other: Reading: 2nd reading. . Hours after challenge: 48.0. Group: other: main test naive control. Dose level: 10%. No with. + reactions: 0.0. Total no. in groups: 10.0.
Reading:
1st reading
Hours after challenge:
24
Group:
positive control
Dose level:
0.07% DNCB
No. with + reactions:
7
Total no. in group:
10
Remarks on result:
other: Reading: 1st reading. . Hours after challenge: 24.0. Group: positive control. Dose level: 0.07% DNCB. No with. + reactions: 7.0. Total no. in groups: 10.0.
Reading:
2nd reading
Hours after challenge:
48
Group:
positive control
Dose level:
0.07 % DNCB
No. with + reactions:
7
Total no. in group:
10
Remarks on result:
other: Reading: 2nd reading. . Hours after challenge: 48.0. Group: positive control. Dose level: 0.07 % DNCB. No with. + reactions: 7.0. Total no. in groups: 10.0.
Reading:
1st reading
Hours after challenge:
24
Group:
other: positive control naive control
Dose level:
0.07 % DNCB
No. with + reactions:
0
Total no. in group:
9
Clinical observations:
1 animal died prior to challenge
Remarks on result:
other: Reading: 1st reading. . Hours after challenge: 24.0. Group: other: positive control naive control. Dose level: 0.07 % DNCB . No with. + reactions: 0.0. Total no. in groups: 9.0. Clinical observations: 1 animal died prior to challenge.
Reading:
2nd reading
Hours after challenge:
48
Group:
other: positive control naive control
Dose level:
0.07% DNCB
No. with + reactions:
0
Total no. in group:
9
Clinical observations:
1 animal died prior to challenge
Remarks on result:
other: Reading: 2nd reading. . Hours after challenge: 48.0. Group: other: positive control naive control. Dose level: 0.07% DNCB. No with. + reactions: 0.0. Total no. in groups: 9.0. Clinical observations: 1 animal died prior to challenge.
Interpretation of results:
not sensitising
Conclusions:
Cyclohexane was not a skin sensitiser under the conditions of the study described. According to EEC Directive 93/21, cyclohexane is not a skin sensitiser.
Executive summary:

The potential of cyclohexane to produce dermal sensitisation in guinea pigs was assessed by the modified Buehler method. Repeated administration of cyclohexane did not produce delayed contact hypersensitivity. The validity of the test procedure was confirmed as DNCB (positive control substance) produced dermal sensitisation in guinea pigs.

Endpoint conclusion
Endpoint conclusion:
no adverse effect observed (not sensitising)
Additional information:

Non-human information

A modified Buehler test was performed by White Eagle Toxicology Laboratories (1996) to assess the sensitisation potential of cyclohexane (method B6 Annex V and according to EC and OECD GLP). During the induction phase, the response ranged from no redness (14/20 animals) to very faint redness on some tested animals. A very faint redness was observed 24 hours after the challenge application in 1/20 tested animals, no reactions were observed in other tested animals or negative controls. There was no incidence of sensitisation among cyclohexane induced and challenged animals

 

Human information

There are no reports of skin sensitisation in humans attributed to this widely-used, high-tonnage material, so a very weak, if any, sensitisation potential can be anticipated for cyclohexane.

Respiratory sensitisation

Endpoint conclusion
Endpoint conclusion:
no study available
Additional information:

No reports of allergic effects on the airways due to cyclohexane exposure have been found.

Justification for classification or non-classification

The animal data supported by the lack of human case studies reporting skin or respiratory sensitisation allow for the overall conclusion that, according to CLP criteria, cyclohexane does not require classification for sensitisation properties.