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Toxicological information

Skin sensitisation

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Administrative data

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:
other: no guideline study,

Data source

Reference
Reference Type:
publication
Title:
Screening of fragrance materials for allergenicity in the guinea pig I. comparison of four testing methods
Author:
Klecak G, Geleick H, Frey JR
Year:
1977
Bibliographic source:
J Soc Cosmet Chem 28, p.53-64

Materials and methods

Principles of method if other than guideline:
The minimum skin irritation concentration of the test substance was determined in an open epicutaneous test;
induction: 6-8 guinea pigs/dose group, undiluted or 30, 10, 3, 1, 0.3, 0.1, 0.03, 0 % solution, 21 d;
challenge: d 21 and d 35
GLP compliance:
no
Type of study:
open epicutaneous test
Justification for non-LLNA method:
The studyy was published in the year 1977. At this time-point no valid guideline for an LLNA was available.

Test material

Constituent 1
Chemical structure
Reference substance name:
Thymol
EC Number:
201-944-8
EC Name:
Thymol
Cas Number:
89-83-8
Molecular formula:
C10H14O
IUPAC Name:
thymol
Details on test material:
Thymol (no data on purity)

In vivo test system

Test animals

Species:
guinea pig
Strain:
Himalayan
Sex:
male/female

Study design: in vivo (non-LLNA)

Inductionopen allclose all
Route:
epicutaneous, open
Vehicle:
other: acetone, ethanol, diethyl phthalate, etc.
Concentration / amount:
undilited, 30, 10, 3, 1, 0.3, 0.1, or 0.03%
Challengeopen allclose all
Route:
epicutaneous, open
Vehicle:
other: acetone, ethanol, diethyl phthalate, etc.
Concentration / amount:
undilited, 30, 10, 3, 1, 0.3, 0.1, or 0.03%
No. of animals per dose:
6

Results and discussion

In vivo (non-LLNA)

Resultsopen allclose all
Reading:
other:
Group:
test chemical
Remarks on result:
other: Thymol was not sensitizing at 10%. Higher concentrations were not used because of systemic toxicity.
Group:
negative control
Remarks on result:
other: see 'Remark'
Remarks:
Solvents, like water, ethanol and acetone, even when applied repeatedly, yielded no macroscopically detectable alteration on the treated skin. When other bases were applied, like Vaseline, diethyl phthalate or polyethylene glycol, additional controls for the vehicles were set in.
Group:
positive control
Remarks on result:
other: A total of 32 compounds described in the literature as allergenic for man were tested by the OET. Of the compounds tested, all those with well-established allergenicity for man were detected by the OET.

Any other information on results incl. tables

Thymol was tested undiluted as well as dissolved in acetone, ethanol,diethylphthalate, etc., at concentrations of 30, 10, 3, 1, 0.3, 0.1, and0.03 per cent in order to establish a dose-response curve making itpossible to determine the minimal irritating and the maximal toleratedconcentrations on an 'all or none' basis.
Induction period: On day 0, 0.1 ml of each undiluted compound and of itsprogressively diluted solutions was applied to an area of measuring 8 cm²on the clipped flank skin of 6 to 8 guinea pigs per concentration group,using 4 to 6 groups for each compound. The applications were repeateddaily for 21 days, always using the same skin site. The application sitewas left uncovered and the reactions were read 24 h after each application.
Challenge procedure: to determine wheather or not allergic contactdermatitis was induced, all groups of guinea pigs previously treated for21 days as described above as well as 6 to 8 untreated controls for each compound,were tested on days 21 and 35 on the contralateral flank with the same compound. Thymol was was negatve in the OET (individual scores not mentioned).

Applicant's summary and conclusion

Interpretation of results:
not sensitising
Remarks:
Migrated information
Executive summary:
Thymol was tested undiluted as well as dissolved in acetone, ethanol, diethylphthalate, etc., at concentrations of 30, 10, 3, 1, 0.3, 0.1, and0.03 per cent in order to establish a dose-response curve making itpossible to determine the minimal irritating and the maximal toleratedconcentrations on an 'all or none' basis.
Induction period: On day 0, 0.1 ml of undiluted thymol and of its progressively diluted solutions was applied to an area of measuring 8 cm² on the clipped flank skin of 6 to 8 guinea pigs per concentration group, using 4 to 6 groups for each compound. The applications were repeated daily for 21 days, always using the same skin site. The application site was left uncovered and the reactions were read 24 h after each application. The maximum nonirritantand the minimal irritating concentrations were determined.
Challenge procedure: to determine wheather or not allergic contact dermatitis was induced, all groups of guinea pigs previously treated for 21 days as described above as well as 6 to 8 untreated controls for each compound, were tested on days 21 and 35 on the contralateral flank with the same compound at the minimal irritating concentration and at some lower nonirritant concentrations.Thymol was negative in this test