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Description of key information

Thioacid was tested for potential contact allergenicity by repeated dermal applications of a 10% w/v solution in 96% ethanol/methyl cellosolve/Tween 80, 45:45:10 parts per volume. 9/10 animals responded positively to challenge with a 5% w/v solution of the test material. In the test system used, thioacid was strongly skin sensitising.

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
Study period:
1987-04-15
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
study well documented, meets generally accepted scientific principles, acceptable for assessment
Reference:
Composition 1
Qualifier:
no guideline followed
Principles of method if other than guideline:
The study was intended to provide evidence on the potential hazards of human skin contact with the test material, GR46580X. The test material was assessed for potential contact sensitivity by the topical method of Levine (1960). This model provides a sensitive method for detecting many strong contact sensitisers as well as some moderate and weak ones and produces an immunological response that is representative of contact allergy in man.
GLP compliance:
not specified
Type of study:
open epicutaneous test
Justification for non-LLNA method:
The test was carried out in-house in 1987, before the LLNA method had been validated
Test material information:
Composition 1
Specific details on test material used for the study:
Batch No: JMR/2592/1
Details on study design:
Not relevant
Details on study design:
Not relevant
Species:
guinea pig
Strain:
Dunkin-Hartley
Sex:
male/female
Details on test animals and environmental conditions:
Each group consisted of five male and five female Dunkin Hartley derived guinea pigs (Porcellus Animal Breeding Ltd.). Positive control (benzylpenicillin, BPEN) and untreated control groups were also included.
No details on environmental conditions have been provided in the study report.
Route:
epicutaneous, open
Vehicle:
other: Materials were dissolved in ECT (96% ethanol/methyl cellosolve/Tween 80, 45:45:10 parts per volume)
Concentration / amount:
Concentration of vehicle: ECT (96% ethanol/methyl cellosolve/Tween 80, 45:45:10 parts by volume).

Concentration of test material:
In a preliminary irritancy titration 10%, 5%, 2.5% and 1% w/v solutions of the test material were applied to the skin of untreated guinea pigs. A 10% w/v solution of the test material was used for induction and a 5% w/v solution for challenge. BPEN was used as a 5% w/v solution for positive control of both induction and challenge.
Day(s)/duration:
16 days for hypersensitivity
Adequacy of induction:
highest concentration used causing mild-to-moderate skin irritation and well-tolerated systemically
No.:
#1
Route:
epicutaneous, open
Vehicle:
other: Materials were dissolved in ECT (96% ethanol/methyl cellosolve/Tween 80, 45:45:10 parts per volume)
Concentration / amount:
5% w/v solution of test material
Day(s)/duration:
approximately 2 days after challenge (on the 29th day of the study)
Adequacy of challenge:
highest non-irritant concentration
No. of animals per dose:
5/sex/group
Details on study design:
Each group consisted of five male and five female Dunkin-Hartley derived quinea pigs (Porcellus Animal Breeding Ltd.). Positive control (benzyl penicillin, BPEN) and untreated control groups were also included. Treatment consisted of six epicutaneous applications of the test (0.05 ml) and control materials on days 1, 3, 5, 8, 10 and 12 of the study using the same skin site for each application (induction procedure). After allowing 16 days for hypersensitivity to develop, the animals were challenged on day 29 for contact sensitivity.
Challenge controls:
On day 29 of the study the animals in the GR46580X group were challenged by topical application of 0.05 ml of a 5% w/v solution of GR46580X and ECT to separate sites on the closely clipped flanks. The positive control group was similarly challenged with 0.05 ml of BPEN solution and ECT. The untreated group received all the challenge materials, 0.05 ml per site. The challenge materials were systematically rotated between challenge sites within each treatment group.
Positive control substance(s):
yes
Remarks:
benzyl penicillin (BPEN) was used as a 5% w/v solution for positive control of both induction and challenge.
Positive control substance(s):
other: Benzyl penicillin
Positive control results:
The positive control material was strongly sensitising : 9/10 animals showed positive reactions to challenge at the 24 hour reading and 10/10 at the 48 hour reading
Reading:
1st reading
Hours after challenge:
24
Group:
test group
Dose level:
0.05 ml of 5% w/v solution of test material in ECT
No. with + reactions:
8
Total no. in group:
10
Remarks on result:
positive indication of skin sensitisation
Reading:
2nd reading
Hours after challenge:
48
Group:
test group
Dose level:
0.05 ml of 5% w/v solution of test material in ECT
No. with + reactions:
9
Total no. in group:
10
Remarks on result:
positive indication of skin sensitisation
Reading:
1st reading
Hours after challenge:
48
Group:
negative control
Dose level:
0.05 ml of 5% w/v solution of test material in ECT
No. with + reactions:
1
Total no. in group:
9
Remarks on result:
no indication of skin sensitisation
Reading:
1st reading
Hours after challenge:
24
Group:
positive control
Dose level:
5% w/v
No. with + reactions:
9
Total no. in group:
10
Remarks on result:
positive indication of skin sensitisation
Reading:
2nd reading
Hours after challenge:
48
Group:
positive control
Dose level:
5% w/v
No. with + reactions:
10
Total no. in group:
10
Remarks on result:
positive indication of skin sensitisation

Animal number 61350 (group 1, untreated) showed scouring on day 9 and died later on the same day. Animal numbers 61369 (group 2, GR46580X), 61354 (group 2) and 61368 (group 2) showed scouring on days 5, 18, and 29 respectively. The remaining animals showed no general loss in condition and there were no significant differences in body weights..

8/10 animals in the GR46580X treated group showed positive reactions to challenge at the 24 hour reading and 9/10 at the 48 hour reading. The positive control material, BPEN, was strongly sensitising: 9/10 animals showed positive reactions to challenge at the 24 hour reading and 10/10 at the 48 hour reading. One (1/9) animal in the untreated control group showed reactions to BPEN and ECT at the 48 hour reading.

There were no significant differences in body weights.

Please see attached 'Skin sensitisation tables' for summary skin sensitisation results and animal body weight changes.

Interpretation of results:
Category 1 (skin sensitising) based on GHS criteria
Conclusions:
GR46580X is considered to be a strong sensitiser
Executive summary:

GR46580X was tested for potential contact allergenicity by repeated dermal applications of a 10% w/v solution in 96% ethanol/methyl cellosolve/Tween 80, 45:45:10 parts per volume. 9/10 animals responded positively to challenge with a 5% w/v solution of the test material. In the test system used GR46580X was strongly skin sensitising. Appropriate precautions should be taken to avoid exposure to this compound.

Endpoint conclusion
Endpoint conclusion:
adverse effect observed (sensitising)

Justification for classification or non-classification

A study on female and male guinea pigs showed strong skin sensitising properties for thioacid. Skin sensitisation results for the substance are sufficient to classify it as Skin Sensitiser 1.