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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
Study period:
26 Aug - 23 Sep 1985
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
guideline study with acceptable restrictions

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
1985
Report date:
1985

Materials and methods

Test guidelineopen allclose all
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.

Test material

Constituent 1
Chemical structure
Reference substance name:
Thiram
EC Number:
205-286-2
EC Name:
Thiram
Cas Number:
137-26-8
Molecular formula:
C6H12N2S4
IUPAC Name:
tetramethylthiuram disulfide

In vivo test system

Test animals

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

Study design: in vivo (non-LLNA)

Induction
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
Challenge
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

Results and discussion

Positive control results:
No positive control was reported.

In vivo (non-LLNA)

Resultsopen allclose all
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

Any other information on results incl. tables

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. 

Applicant's summary and conclusion

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.