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Administrative data

Description of key information

Source, RA-A, CAS 137-26-8, key, Split Adjuvant Test (guinea pig, OECD 406 and EPA OPP 81 -5, GLP): skin sensitizing

Key value for chemical safety assessment

Skin sensitisation

Link to relevant study records

Referenceopen allclose all

Endpoint:
skin sensitisation: in vivo (non-LLNA)
Type of information:
read-across from supporting substance (structural analogue or surrogate)
Adequacy of study:
key study
Justification for type of information:
refer to analogue justification provided in IUCLID section 13.
Reason / purpose for cross-reference:
read-across source
Key result
Reading:
1st reading
Hours after challenge:
24
Group:
test chemical
Dose level:
25%
No. with + reactions:
8
Total no. in group:
20
Clinical observations:
confluent skin reddening beyond the exposed area
Remarks on result:
other: source substance, 8 animals had a grade 1 reaction which was also observed in 1 control animal, 8 animals had a grade 2 reaction.
Key result
Reading:
2nd reading
Hours after challenge:
48
Group:
test chemical
Dose level:
25%
No. with + reactions:
6
Total no. in group:
20
Clinical observations:
confluent skin reddening beyond the exposed area
Remarks on result:
other: source substance, 9 animals had a grade 1 reaction, 6 animals had a grade 2 reaction.
Key result
Reading:
1st reading
Hours after challenge:
24
Group:
negative control
No. with + reactions:
1
Total no. in group:
10
Remarks on result:
other: source substance, 1 animal had a grade 1 reaction
Key result
Reading:
2nd reading
Hours after challenge:
48
Group:
negative control
No. with + reactions:
0
Total no. in group:
10
Remarks on result:
other: source substance, no indication of skin sensitisation
Interpretation of results:
other: According to the classification criteria of the CLP Regulation (EU) No. 1272/2008, the substance should be classified as Skin Sens. Cat 1 (H317).
Conclusions:
The study (Split Adjuvant Test) was conducted with the source substance according to EPA OPP 81-6 and GLP and is thus considered valid and reliable.
Under the test conditions, the test substance produced a sensitizing reaction in guinea pigs with a skin sensitisation rate of 40%. According to the classification criteria of the CLP Regulation (EU) No. 1272/2008, classification for skin sensitisation Category 1 (H317) is warranted.
Endpoint:
skin sensitisation: in vivo (non-LLNA)
Type of information:
experimental study
Adequacy of study:
key study
Study period:
26 Aug - 23 Sep 1985
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
guideline study with acceptable restrictions
Qualifier:
equivalent or similar to guideline
Guideline:
OECD Guideline 406 (Skin Sensitisation)
Version / remarks:
adopted in 2021
Deviations:
yes
Remarks:
The concentration used for induction did not induce skin irritation. No positive controls. No challenge control. GPMT is the preferred method.
Qualifier:
according to guideline
Guideline:
EPA OPP 81-6 (Skin Sensitisation)
GLP compliance:
yes
Type of study:
split adjuvant test
Justification for non-LLNA method:
The study was initiated prior to the implementation of the LLNA method.
Species:
guinea pig
Strain:
Dunkin-Hartley
Sex:
female
Details on test animals and environmental conditions:
TEST ANIMALS
- Source: Olac, Great Britain
- Females nulliparous and non-pregnant: not specified
- Microbiological status of animals: SPF-quality
- Age at study initiation: adult, not further specified
- Weight at study initiation: approx. 500 - 700 g (5 days before administration of the test substance)
- Housing: metal cages with wire-mesh floors, 2 animals per cage
- Diet: standard guinea pig diet, including ascorbic acid (1600 mg/kg bw), obtained from Hope Farms, Woerden. In additon, once a week, hay was provided.
- Water: not specified but assumed to be tap water, ad libitum
- Acclimation period: approx. 5 weeks
- Indication of any skin lesions: no

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 20.5 - 22.5
- Humidity (%): 50 - 80
- Air changes (per hr): not reported
- Photoperiod (hrs dark / hrs light): 12/12

- IN-LIFE DATES: From: 26 Aug 1985 To: 23 Sep 1985
Route:
epicutaneous, occlusive
Vehicle:
petrolatum
Concentration / amount:
25%
Day(s)/duration:
Day 0, 2, 4, 7, wrapping was removed on Day 9
Adequacy of induction:
other: concentration applied was non-irritating
No.:
#1
Route:
epicutaneous, occlusive
Vehicle:
petrolatum
Concentration / amount:
25 %
Day(s)/duration:
at Day 21 for 24 h
Adequacy of challenge:
not specified
No. of animals per dose:
20 (test group), 10 controls
Details on study design:
RANGE FINDING TESTS:
In a primary irritation test with four additional animals the concentration of 25% (W/W) in petrolatum exposed for 24 hours using the same dressing as in the challenge was found to be non-irritating and therefore, was used for both induction and challenge.


MAIN STUDY
A. INDUCTION EXPOSURE
- No. of exposures: 4 (epicutaneous)
- Exposure period: wrapping were removed on Day 9
Before the first exposure, dry ice was applied for 5 sec with firm pressure to the shaved exposure side.
Epicutaneous 1: 0.2 mL of test substance, 25% (w/w) in petrolatum was applied on Day 1
Epicutaneous 2: 0.2 mL of test substance, 25% (w/w) in petrolatum was applied on Day 2
Injection 1: 0.1 mL of Freund’s complete adjuvant was injected intradermally in both sides of the exposure site on Day 4.
Epicutaneous 3: 0.2 mL of test substance, 25% (w/w) in petrolatum applied on Day 4
Epicutaneous 4: 0.2 mL of test substance, 25% (w/w) in petrolatum was applied on Day 7
- Control group: Animals of the control group received injections of Freund’s complete adjuvant on Day 4 only.
- Site: back just behind the shoulder girtle
- Frequency of applications: 4 times
- Duration: continiously up to Day 9
- Concentrations: 25% (w/w) in petrolatum

B. CHALLENGE EXPOSURE
- No. of exposures: 1
- Days of challenge: on Day 21
- Exposure period: 24 h
- Test groups: test substance and negative control
- Control group: test substance and negative control
- Site: flank
- Concentrations: 0.1 mL of test substance, 25% (w/w) in petrolatum
- Evaluation (hr after challenge): 24 and 48 h after removal of the dressing
Challenge controls:
No
Positive control substance(s):
no
Positive control results:
No positive control was reported.
Key result
Reading:
1st reading
Hours after challenge:
24
Group:
test chemical
Dose level:
25 %
No. with + reactions:
8
Total no. in group:
20
Clinical observations:
confluent skin reddening beyond the exposed area
Remarks on result:
other: 8 animals had a grade 1 reaction which was also observed in 1 control animal, 8 animals had a grade 2 reaction.
Key result
Reading:
2nd reading
Hours after challenge:
48
Group:
test chemical
Dose level:
25 %
No. with + reactions:
6
Total no. in group:
20
Clinical observations:
confluent skin reddening beyond the exposed area
Remarks on result:
other: 9 animals had a grade 1 reaction, 6 animals had a grade 2 reaction.
Key result
Reading:
1st reading
Hours after challenge:
24
Group:
negative control
No. with + reactions:
1
Total no. in group:
10
Remarks on result:
other: 1 animal had a grade 1 reaction
Key result
Reading:
2nd reading
Hours after challenge:
48
Group:
negative control
No. with + reactions:
0
Total no. in group:
10
Remarks on result:
no indication of skin sensitisation

Skin reactions
Control group
There were no skin reactions observed in the control animals, except for one animal which showed red spots in reaction in the first reading after the challenge exposure. This skin reaction was scored with grade 1.

Test substance group
The test substance, suspended in petrolatum at 25% and administered epicutaneously to guinea pigs in the challenge phase, resulted in a positive skin response (grade 2) in 8 animals 24 h after the challenge phase and 6 animals 48 h after the challenge phase. This corresponds to a sensitization rate of 40%.

 

Summarized results can be found in Attachment 1 in the attached background material. 

Interpretation of results:
other: According to the classification criteria of the CLP Regulation (EU) No. 1272/2008, the substance should be classified as Skin Sens. Cat 1 (H317)..
Conclusions:
The study (Split Adjuvant Test) was conducted according to EPA OPP 81-6 and GLP and is considered valid and reliable.
Under the test conditions, the test substance produced a sensitizing reactionin guinea pigs with a skin sensitisation rate of 40%. According to the classification criteria of the CLP Regulation (EU) No. 1272/2008, classification for skin sensitisation Category 1 (H317) is warranted.
Endpoint conclusion
Endpoint conclusion:
adverse effect observed (sensitising)
Additional information:

There are no data on sensitisation with disulfiram. Therefore, its sensitisation potential is assessed using read-across from a study conducted with the source substance, thiram (CAS 137 -26 -8). (For detailed information on the justification of read-across, please refer to the analogue justification document attached in IUCLID section 13).

 

One reliable animal sensitisation study performed according to EPA-OPP 81-6 (Split Adjuvant Test) is available for thiram (Report number 0174/263). A 25% dilution of the substance caused sensitisation in 8/20 female guinea pigs 24 hours after challenge. No irritation was observed in the animals. Thus, under the test conditions, the test substance produced a sensitizing reaction in guinea pigs with a skin sensitisation rate of 40%. According to the classification criteria of the CLP Regulation (EU) No. 1272/2008, classification for skin sensitisation Category 1 (H317) is warranted.

Patch testing in sensitised humans, the pure substance induced a reaction, while the substance formulated into rubber did not cause any effects (Crabtree, 1978).

Respiratory sensitisation

Endpoint conclusion
Endpoint conclusion:
no study available

Justification for classification or non-classification

Based on the available data for the read across source substance, the test item induced skin sensitization in guinea pigs and human volunteers. Therefore, the source and the target substance is classified as skin sensitising category 1 (H317) according to Regulation (EC) No 1272/2008 and Annex VI of Regulation (EC) No 1272/2008 (CLP Regulation, Index No. 006-079-00-8 (target substance)).