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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:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
guideline study with acceptable restrictions
Remarks:
no data on positive control/strain sensitivity
Qualifier:
according to guideline
Guideline:
OECD Guideline 406 (Skin Sensitisation)
Version / remarks:
adopted in May 1981
Deviations:
yes
Remarks:
(no data on positive control/strain sensitivity)
GLP compliance:
no
Remarks:
study performed prior to implementation of GLP
Type of study:
guinea pig maximisation test
Justification for non-LLNA method:
The LLNA method was not available yet by the time the study was conducted.
This test is considered appropriate and it is not justified to conduct an additional LLNA study due to animal welfare.
Species:
guinea pig
Strain:
other: albino guinea pig, Bor:DHPW
Sex:
female
Details on test animals and environmental conditions:
TEST ANIMALS
- Mean weight at study initiation: 359.1 g (test group), 378.9 g (control group)
- Housing: 1-5 animals/cage in Makrolon cages type IV
- Diet: G4 Alleindiaet fuer Meerschweinchen (Ssniff Spezialfutter GmbH, Soest, Germany); ad libitum
- Water: tap water; ad libitum
- Acclimation period: 4-8 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: 01 Mar 1988 To: 25 Mar 1988
Route:
intradermal and epicutaneous
Vehicle:
corn oil
Concentration / amount:
intradermal induction: 5% in vehicle
epicutaneous induction: 100%
epicutaneous challenge: 100%

Route:
epicutaneous, occlusive
Vehicle:
corn oil
Concentration / amount:
intradermal induction: 5% in vehicle
epicutaneous induction: 100%
epicutaneous challenge: 100%

No. of animals per dose:
test group: 20
control group: 10
Details on study design:
A. INDUCTION EXPOSURE
- No. of exposures: 2 (intradermal and epicutaneous, respectively)
- Exposure period: single injection (intradermal) and 48 h (epicutaneous)

- Test groups:
Intradermal (3 pairs of injections (0.1 mL)):
Injection 1: a 1:1 mixture Freunds complete adjuvant (FCA)/water
Injection 2: 5% test substance in corn oil
Injection 3: 5% test substance in a 1:1 mixture FCA/corn oil
Epicutaneous: 100% test substance

- Control group:
Intradermal (3 pairs of injections):
Injection 1: a 1:1 mixture Freunds complete adjuvant (FCA)/water
Injection 2: corn oil
Injection 3: a 1:1 mixture FCA/corn oil
Epicutaneous: corn oil

- Site: shoulder region (intradermal and epicutaneous)
- Frequency of applications: every 7 days
- Duration: Days 0-8
- Concentrations: intradermal 5%, epicutaneous 100%

B. CHALLENGE EXPOSURE
- No. of exposures: 1 challenge
- Day of challenge: 21 (challenge)
- Exposure period: 24 h
- Test groups: 100% test substance
- Control group: 100% test substance
- Site: left flank
- Concentrations: 100%
- Evaluation (hr after challenge): 24 and 48 h

OTHER: For the epicutaneous treatments, the test item was heated above the melting point to approx. 70 °C. The patches were soaked with the test substance and applied to the skin after cooling down. The patches were covered with a 6 x 6 cm² leukoflex-tape and fixed with an elastic bandage.
Positive control substance(s):
not specified
Reading:
1st reading
Hours after challenge:
24
Group:
test chemical
Dose level:
induction: 5% intradermal, 100% epicutaneous; challenge: 100% epicutaneous
No. with + reactions:
0
Total no. in group:
20
Clinical observations:
substance residues in 4/20 animals
Remarks on result:
other: see Remark
Remarks:
Reading: 1st reading. . Hours after challenge: 24.0. Group: test group. Dose level: induction: 5% intradermal, 100% epicutaneous; challenge: 100% epicutaneous. No with. + reactions: 0.0. Total no. in groups: 20.0. Clinical observations: substance residues in 4/20 animals.
Reading:
2nd reading
Hours after challenge:
48
Group:
test chemical
Dose level:
induction: 5% intradermal, 100% epicutaneous; challenge: 100% epicutaneous
No. with + reactions:
0
Total no. in group:
20
Clinical observations:
substance residues in 1/20 animals
Remarks on result:
other: see Remark
Remarks:
Reading: 2nd reading. . Hours after challenge: 48.0. Group: test group. Dose level: induction: 5% intradermal, 100% epicutaneous; challenge: 100% epicutaneous. No with. + reactions: 0.0. Total no. in groups: 20.0. Clinical observations: substance residues in 1/20 animals.
Reading:
1st reading
Hours after challenge:
24
Group:
negative control
Dose level:
induction: 0% intradermal, 0% epicutaneous; challenge: 100% epicutaneous
No. with + reactions:
0
Total no. in group:
10
Clinical observations:
substance residues in 6/10 animals
Remarks on result:
other: see Remark
Remarks:
Reading: 1st reading. . Hours after challenge: 24.0. Group: negative control. Dose level: induction: 0% intradermal, 0% epicutaneous; challenge: 100% epicutaneous. No with. + reactions: 0.0. Total no. in groups: 10.0. Clinical observations: substance residues in 6/10 animals.
Reading:
2nd reading
Hours after challenge:
48
Group:
negative control
Dose level:
induction: 0% intradermal, 0% epicutaneous; challenge: 100% epicutaneous
No. with + reactions:
0
Total no. in group:
10
Clinical observations:
substance residues in 1/10 animals
Remarks on result:
other: see Remark
Remarks:
Reading: 2nd reading. . Hours after challenge: 48.0. Group: negative control. Dose level: induction: 0% intradermal, 0% epicutaneous; challenge: 100% epicutaneous. No with. + reactions: 0.0. Total no. in groups: 10.0. Clinical observations: substance residues in 1/10 animals.
Reading:
1st reading
Hours after challenge:
24
Group:
positive control
Remarks on result:
not measured/tested
Reading:
2nd reading
Hours after challenge:
48
Group:
positive control
Remarks on result:
not measured/tested

Local findings

- after intradermal induction: pronounced erythema and edema including slight necrosis at the FCA/water injection sites (test and control group) and the FCA/vehicle injection site (control group); pronounced erythema and edema at the test item/vehicle injection site (test group); slight erythema and edema at the vehicle injection site (control group) and pronounced erythema and edema including pronounced necrosis at the test item/FCA/vehicle injection site (test group)

- after epicutaneous induction (48 h): bloody inflammation at all sites previously treated with FCA (test group and control group); encrustation after 24 h

Body weight

No effects on body weight gain was seen during the study.

Interpretation of results:
GHS criteria not met
Remarks:
Migrated information
Conclusions:
The test item showed no sensitising potential in a guinea pig maximisation test.
Endpoint conclusion
Endpoint conclusion:
no adverse effect observed (not sensitising)
Additional information:

The skin sensitising potential of 4-tert-butylcyclohexanol was assessed in a guinea pig maximisation test according to OECD Guideline 406 adopted in 1981 (88-0486-DKT). 20 female guinea pigs (Pirbright White, Dunkin Hartley, BOR:DHPW) were induced intradermally with 3 pairs of injections (0.1 mL 1:1 mixture FCA/water; 0.1 mL 5% test substance in corn oil; 0.1 mL 5% test substance in a 1:1 mixture FCA/corn oil). The control group, consisting of 10 animals, was injected with the vehicle only and/or FCA. One week later, the epicutaneous induction treatment with the indiluted test substance (100%) or the vehicle alone was conducted in the treated or control animals on the shoulder regions of intradermal injections for a period of 48 h under occlusive conditions. Pronounced local reactions (erythema, edema, necrosis, bloody inflammation) were observed after both induction procedures. On day 21, the challenge treatment was performed by topical application of the undiluted test substance to the skin of all animals (test and control group) for 24 h under occlusive conditions. No cutaneous reactions were provoked 24 and 48 h after challenge treatment with the undiluted test substance in any of the animals. Only substance residues were seen in some animals of both groups. No effects on body weight gain were observed during the study. Based on these results of the guinea pig maximisation test 4-tert-butylcyclohexanol is considered not to be sensitising to skin.

The non-sensitising potential of the test substance was further supported in a human maximization test (Kligman, 1966) carried out on 25 volunteers. No sensitisation reactions were produced at a concentration of 4% 4-tert-butylcyclohexanol in petrolatum (Opdyke, 1974).

References:

Kligman, 1966. The identification of contact allergens by human assay. III. The maximization test. A procedure for screening and rating contact sensitizers, J. invest. Derm. 47: 393


Respiratory sensitisation

Endpoint conclusion
Endpoint conclusion:
no study available
Additional information:

No data on respiratory sensitisation. Study not required according to Annex VII-X of Regulation (EC) No 1907/2006.

Justification for classification or non-classification

The available data on skin sensitisation of 4-tert-butylcylohexanol 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.