Registration Dossier

Administrative data

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 guideline study

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
1994
Report date:
1994

Materials and methods

Test guideline
Qualifier:
according to guideline
Guideline:
OECD Guideline 406 (Skin Sensitisation)
Deviations:
no
GLP compliance:
yes
Type of study:
guinea pig maximisation test

Test material

Constituent 1
Chemical structure
Reference substance name:
Thioacetic acid
EC Number:
208-063-8
EC Name:
Thioacetic acid
Cas Number:
507-09-5
Molecular formula:
C2H4OS
IUPAC Name:
ethanethioic S-acid
Test material form:
other: liquid
Details on test material:
- Name of test material (as cited in study report): Thioacetic acid
- batch D 60018
- purity 99.78%.

In vivo test system

Test animals

Species:
guinea pig
Strain:
Dunkin-Hartley
Sex:
male/female
Details on test animals and environmental conditions:
TEST ANIMALS
- Source: Centre d'Elevage Lebeau, 78950 Gambais, France.
- Age at study initiation: no data
- Weight at study initiation: 410 ± 22 g for the males and 404 ± 23 g for the females
- Housing: individually in polycarbonate cages (48 x 27 x 20 cm)
- Diet: free access to "Guinea-pigs sustenance reference 106 diet"
- Water: water filtered by a F.G. Millipore membrane (0.22 micron) ad libitum
- Acclimation period: at least 5 days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 22 ± 3
- Humidity (%): 50 ± 20
- Air changes (per hr): The air was non-recycled and filtered
- Photoperiod (hrs dark / hrs light): 12 h/12 h

Study design: in vivo (non-LLNA)

Inductionopen allclose all
Route:
intradermal and epicutaneous
Vehicle:
paraffin oil
Concentration / amount:
1st application: Induction 1 % intracutaneous
2nd application: Induction 10 % occlusive epicutaneous
3rd application: Challenge 10 % occlusive epicutaneous
Challengeopen allclose all
Route:
epicutaneous, occlusive
Vehicle:
paraffin oil
Concentration / amount:
1st application: Induction 1 % intracutaneous
2nd application: Induction 10 % occlusive epicutaneous
3rd application: Challenge 10 % occlusive epicutaneous
No. of animals per dose:
10 controls, 20 treated
Positive control substance(s):
yes
Remarks:
dinitro-2,4-chlorobenzene

Results and discussion

Positive control results:
The guinea-pigs which were used showed a satisfactory sensitization response in 100% animals using a positive sensitizer.

In vivo (non-LLNA)

Resultsopen allclose all
Reading:
1st reading
Hours after challenge:
24
Group:
test chemical
Dose level:
10%
No. with + reactions:
14
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: 14.0. Total no. in groups: 20.0.
Reading:
2nd reading
Hours after challenge:
48
Group:
test chemical
Dose level:
10%
No. with + reactions:
9
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: 9.0. Total no. in groups: 20.0.
Reading:
other: 1st & 2nd 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: other: 1st & 2nd reading. . Hours after challenge: 24.0. Group: negative control. Dose level: 10%. No with. + reactions: 0.0. Total no. in groups: 10.0.

Any other information on results incl. tables

No clinical signs and no deaths were noted during the study. Sensitization skin reactions characterised by a well-defined and a moderate to severe erythema were observed after 24 hours on the right flank of 14/20 treated animals. No oedema was observed. Inconclusive evidence of sensitization skin reactions (very slight erythema, score of 1) were noted in 6/20 treated animals. After 48 hours, intensity of erythema reversed slightly. A dryness of the skin was noted after 48 hours in 19/20 treated animals. No oedema was observed.

Applicant's summary and conclusion

Interpretation of results:
other: sensitising cat. 1A
Remarks:
Criteria used for interpretation of results: EU
Conclusions:
THIOACETIC ACID, induced positive skin sensitization cutaneous reactions in 14/20 (60%) guinea-pigs.
Executive summary:

The potential of THIOACETIC ACID, to induce delayed contact hypersensitivity following intradermal injection and cutaneous application was evaluated in guinea-pigs according to the maximization method of Magnusson and Kligman and O.E.C.D. (No. 406, 12th May 1981). The study was conducted in compliance with the Principles of Good Laboratory Practice Regulations.

Thirty guinea-pigs (15 males and 15 females) were allocated to 2 groups: a control group 1 (5 males and 5 females) and a treated group 2 (10 males and 10 females).

The sensitization potential of the test substance was evaluated after a 10-day induction periodduring which time the animals were treated with the vehicle (control group) or the test substance(treated group). On day 1, in presence of Freund's complete adjuvant, 0.1 ml of the test substance at a concentration of 1% in the vehicle was administered by intradermal route. On day 8, 0.5 ml of the test substance at a concentration of 10% in the vehicle was applied by cutaneous route during 48 hours by means of an occlusive dressing. After a period of 12 days without treatment, a challenge cutaneous application of 0.5 ml of the vehicle (left flank) and 0.5 ml of the test substance at a concentration of 10% in the vehicle (right flank) were admi­nistered to ail animals.

The test substance and the vehicle were prepared on a dry compress then were applied to the skin and held in place for 24 hours by means of an occlusive dressing. Cutaneous reactions on the challenge application sites were then evaluated 24 and 48 hours after removal of the dressing.

After the final scoring period, the animals were sacrificed and cutaneous samples were taken from the challenge application sites from ail the animals. No histological examination was per­formed on the cutaneous samples.

The sensitivity of the guinea-pigs in the laboratory experimental conditions were checked in a recent study with a positive sensitizer: Dinitro 2.4 Chlorobenzene. During induction period the test substance was applied at 0.05% (day 1) and 0.5% (day 8) concentrations. At cutaneous challenge application, 0.1% and 0.5% were tested on both flanks.

No clinical signs and no deaths were noted during the study.

Sensitization skin reactions characterised by a well-defined and a moderate to severe erythema were observed after 24 hours on the right flank of 14/20 treated animals. No oedema was observed.

Inconclusive evidence of sensitization skin reactions (very slight erythema, score of 1) were noted in 6/20 treated animals.

After 48 hours, intensity of erythema reversed slightly.

A dryness of the skin was noted after 48 hours in 19/20 treated animals.No oedema was observed.

The guinea-pigs which were used showed a satisfactory sensitization response in 100% animals using a positive sensitizer.

THIOACETIC ACID, induced positive skin sensitization cutaneous reactions in 14/20 (60%) guinea-pigs.