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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:
1993-03-11 - 1993-04-22
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
other: GLP-Guideline study without deviations on ‘1,3,4-Thiadiazolidine-2,5-dithione, reaction products with hydrogen peroxide and tert-dodecanethiol’.

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
1993
Report date:
1993

Materials and methods

Test guideline
Qualifier:
according to guideline
Guideline:
OECD Guideline 406 (Skin Sensitisation)
Deviations:
no
GLP compliance:
yes (incl. QA statement)
Remarks:
Umweltministerium Baden-Württemberg, Stuttgart, Germany
Type of study:
Buehler test
Justification for non-LLNA method:
There was a OECD 406 available which had been performed in 1993. It fulfills all the criteria and there was no need to do further animal testing (LLNA)

Test material

Constituent 1
Reference substance name:
5-[(2,2-dimethyldecyl)disulfanyl]-1,3,4-thiadiazole-2-thiol; bis[(2,2-dimethyldecyl)disulfanyl]-1,3,4-thiadiazole
EC Number:
939-692-2
Cas Number:
1474044-73-9
Molecular formula:
not applicable (UVCB substance)
IUPAC Name:
5-[(2,2-dimethyldecyl)disulfanyl]-1,3,4-thiadiazole-2-thiol; bis[(2,2-dimethyldecyl)disulfanyl]-1,3,4-thiadiazole
Test material form:
other: liquid
Details on test material:
- Physical state: light-brown liquid
- Stability under test conditions: stable at dry storage (20 °C)

In vivo test system

Test animals

Species:
guinea pig
Strain:
other: Pirbright White
Sex:
male/female
Details on test animals and environmental conditions:
TEST ANIMALS
- Source: Interfauna, Süddeutsche Versuchstierfarm, Tuttlingen, Germany
- Age at study initiation: younger than 1 year
- Weight at study initiation: 333 g (males), 273 g (females), mean values
- Housing: individually in Macrolon cages (area 780 cm²)
- Diet: Raiffeisen-Ringfutter, dry food 52/P (Raiffeisen Kraftfutterwerk Kehl, Germany), ad libitum
- Water: community tap water supplemented with 20 mg/100 mL L-ascorbic acid and 100 mg/100 mL citric acid, ad libitum
- Acclimation period: 5 days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 20-22
- Humidity (%): 30-70
- Photoperiod (hrs dark / hrs light): 12 / 12

Study design: in vivo (non-LLNA)

Inductionopen allclose all
Route:
epicutaneous, occlusive
Vehicle:
other: Pilot study: sesame oil (Carl Roth GmbH&Co., item No. 9335); Main study: unchanged (no vehicle)
Concentration / amount:
Pilot study: 12.5 %, 25 %, 50 %, 100 %
Main study: 100 % for induction and challenge
Challengeopen allclose all
Route:
epicutaneous, occlusive
Vehicle:
other: Pilot study: sesame oil (Carl Roth GmbH&Co., item No. 9335); Main study: unchanged (no vehicle)
Concentration / amount:
Pilot study: 12.5 %, 25 %, 50 %, 100 %
Main study: 100 % for induction and challenge
No. of animals per dose:
Pilot study: 2
Main study: 10 (5 males and 5 females)
Details on study design:
PILOT STUDY:
- No. of exposures: 1
- Exposure period: 6 h
- Site: clipped and covered by occlusive bandage
- Concentrations: 0.3 mL of 0%, 12.5%, 50%, 100%
- Evaluation: 1, 24, 48 and 72 h after application

MAIN STUDY
A. INDUCTION EXPOSURE
- No. of exposures: 3
- Exposure period: 6 h
- Test groups: test substance
- Control group: untreated
- Site: clipped area of 4x6 cm² of the left flank (24 h before application), covered with occlusive bandage made of an impermeable plastic tape and an elastic gauze
- Frequency of applications: every 7 days
- Duration: 14 days
- Concentrations: 100% (0.3 mL)

B. CHALLENGE EXPOSURE
- No. of exposures: 1
- Day(s) of challenge: day 28
- Exposure period: 6 h
- Test groups: test substance
- Control group: test substance
- Site: clipped area of 4x6 cm² of the right flank (24 h before application), covered with occlusive bandage made of an impermeable plastic tape and an elastic gauze
- Concentrations: 100% (0.3 mL)
- Evaluation (hr after challenge): 24 and 48 h after application
Challenge controls:
No information available.
Positive control substance(s):
not specified
Remarks:
No positive control substance recorded.

Results and discussion

Positive control results:
Not applicable.

In vivo (non-LLNA)

Resultsopen allclose all
Reading:
1st reading
Hours after challenge:
24
Group:
test chemical
Dose level:
100%
No. with + reactions:
0
Total no. in group:
10
Clinical observations:
none
Remarks on result:
other: Reading: 1st reading. . Hours after challenge: 24.0. Group: test group. Dose level: 100%. No with. + reactions: 0.0. Total no. in groups: 10.0. Clinical observations: none.
Reading:
1st reading
Hours after challenge:
24
Group:
negative control
Dose level:
100%
No. with + reactions:
0
Total no. in group:
10
Clinical observations:
none
Remarks on result:
other: Reading: 1st reading. . Hours after challenge: 24.0. Group: negative control. Dose level: 100%. No with. + reactions: 0.0. Total no. in groups: 10.0. Clinical observations: none.
Reading:
2nd reading
Hours after challenge:
48
Group:
test chemical
Dose level:
100%
No. with + reactions:
0
Total no. in group:
10
Clinical observations:
none
Remarks on result:
other: Reading: 2nd reading. . Hours after challenge: 48.0. Group: test group. Dose level: 100%. No with. + reactions: 0.0. Total no. in groups: 10.0. Clinical observations: none.
Reading:
2nd reading
Hours after challenge:
48
Group:
negative control
Dose level:
100%
No. with + reactions:
0
Total no. in group:
10
Clinical observations:
none
Remarks on result:
other: Reading: 2nd reading. . Hours after challenge: 48.0. Group: negative control. Dose level: 100%. No with. + reactions: 0.0. Total no. in groups: 10.0. Clinical observations: none.
Group:
positive control
Remarks on result:
not measured/tested

Any other information on results incl. tables

Result of pilot study:

Skin reactions:
Time after application
Concentration Animal No. 1 h 24 h 48 h 72 h
12.50% 1 none none none none
2 none none none none
25.00% 1 none none none none
2 none none none none
50.00% 1 none none none none
2 none none none none
100.00% 1 none none none none
2 none none none none
control 1 none none none none
2 none none none none

None of the animals died or showed signs of toxicological symptoms. The behaviour pattern was not different to that of non treated guinea pigs (control).

Main study:

Body weight (g) on day
Animal Number -5 0 7 14 21 28 29 30
Test Group Males 11 332 380 425 479 510 590 587 587
12 367 433 461 518 530 580 585 586
13 329 372 400 457 479 613 624 623
14 335 378 418 431 458 530 544 545
15 329 378 416 472 507 566 547 546
mean 338 388 424 391 497 576 577 577
Females 16 200 247 240 272 320 418 425 425
17 243 300 337 394 416 518 500 503
18 300 310 314 385 412 508 507 510
19 244 265 310 355 389 452 455 455
20 212 260 275 348 359 485 470 469
mean 240 276 295 351 379 476 471 472
Control Group Males 21 265 305 330 355 418 481 502 505
22 327 359 400 150 479 576 567 570
23 348 384 412 474 499 552 558 558
24 327 335 370 437 458 531 545 545
25 349 400 449 515 540 647 646 647
mean 323 357 392 386 479 557 564 565
Females 26 280 325 350 410 447 500 507 510
27 289 332 368 424 450 519 530 528
28 265 312 350 391 428 442 500 499
29 337 353 370 399 432 402 468 470
30 352 395 441 480 516 528 565 567
mean 305 343 376 421 455 478 514 515

Applicant's summary and conclusion

Interpretation of results:
not sensitising
Remarks:
Criteria used for interpretation of results: EU-GHS
Conclusions:
The study was conducted according to OECD Guideline 406 and is considered as valid. The control group also showed no skin reactions.
As no animal in the test group showed any skin reaction after application of the test substance a classification is not required, neither according to EU Directive 67/548/EEC nor according to EC Regulation 1272/2008. The test item can be regarded as non-sensitising.
Executive summary:

The test substance (1,3,4-Thiadiazolidine-2,5-dithione, reaction products with hydrogen peroxide and tert-dodecanethiol) was tested in a GLP study according to OECD Guideline 406 for its sensitising potential in order to determine whether there is any specific (sensitising) or non-specific (irritant) stimulating potential of the test substance (Biochem, Grunert, 1993). In a pilot study the test item was tested dermally, occlusive and thinned to 12.5 %, 25 %, 50 % and 100 % in sesame oil over a period of 6h with a single exposure. Each dose group consisted of 2 guinea pigs (Pirbright White, age < 1a), an area of 4 cm x 6 cm was clipped and exposed to 0.3 mL of the test item, the post-exposure period was 72 h. Additionally, a control group was not exposed to the test item. After 1 h, 1 d, 2 d and 3 d the treated skin was checked for irritation. At no time point and in no animal any skin reactions were observed. Therefore, the undiluted test item was chosen for the main study. In the main study, a test group and a control group consisting each of 10 guinea pigs (5 males / 5 females) were used. The test group was exposed occlusive during the induction phase three times (day 0, 7, 14) over 6 h to 0.3 ml the test item onto 4 cm x 6 cm clipped skin. The control group was not exposed to the test item but was treated the same way regarding clipping and the occlusive bandage. After two weeks free from all treatment the test item was applied similar to the induction phase on day 28 to both groups (test animals as well as control animals) over 6 h. 24 h and 48 h after the challenge skin readings were performed. No animal, neither control nor test group, exhibited any skin reaction. Therefore, the substance can be regarded as non-sensitising.