Registration Dossier

Administrative data

Endpoint:
sensitisation data (humans)
Type of information:
experimental study
Adequacy of study:
supporting study
Study period:
January 2000 - March 2007
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
other: The study was not conducted according to GLP and test guidelines. It does not contain sufficient amount of data for the interpretation of the results as the method is not described in detail.

Data source

Reference
Reference Type:
publication
Title:
Contact allergy to 2,5-dimercapto-1,3,4-thiadiazole and phenyl-α-naphtylamine, allergens in industrial greases and lubricant oils – contact allergy to water-insoluble greases is uncommon but needs to be considered in some workers
Author:
Finnish Institue of Occupational Health (FIOH), Control of Hypersensitivity Diseases and Occupational Medicine, Helsinki, Finland
Year:
2008
Bibliographic source:
Contact Dermatitis 2008: 58: 93-96

Materials and methods

Type of sensitisation studied:
skin
Study type:
case report
Principles of method if other than guideline:
Patch test was performed using the Finn Chambers on Scanpore tape (Epitest, Tuusula, Finland). The following allergens in greases and lubricants were tested:2,5-dimercapto-1,3,4-thiadiazole, phenyl-α-naphtylamine, tertiary butyl hydroquinone, EHZDTP, coconut diethanolamide and dipentene.
GLP compliance:
not specified
Remarks:
not applicable

Test material

Reference
Name:
Unnamed
Type:
Constituent
Details on test material:
Product number: CAS No: 1072-71-5; 1,3,4-Thiadiazole-2,5-dithiol
Description: aromatic compound in oils and greases

Method

Type of population:
occupational
Ethical approval:
not specified
Subjects:
- Number of cases: 2 out of 112 patients
- Sex: Male
- Age: 50-52
- Race: Not Designated

Patient 1 was a 50-year-old male computer numerical control machinist who had previously had occasional skin symptoms on various parts of his body, including foot dermatitis while using protection shoes. In 1999 he developed hand dermatitis for the first time, and it healed during sick leaves.

Patient 2 was a 52-year-old male lorry assembler who developed work-related eczema on his eyelids and around his eyes in 2003.
Route of administration:
dermal
Details on study design:
TYPE OF TEST USED: patch test (epicutaneous test)

ADMINISTRATION
- Type of application: epicutaneous
- Description of patch: Finn Chambers on Scanpore tape
- Concentration: Patient 1: guide-way oil at 20%, first time: 2,5-Dimercapto-1,3,4-thiadiazole 20%, 10%, 3.2% and 1%,
second time: 2,5-Dimercapto-1,3,4-thiadiazole 2%, 1%, 0.32% and 0.1%
Patient 2: first time: 2,5-dimercapto-1,3,4-thiadiazole 1 %, second time: with the dilution series of the centre grease: 100–3.2% concentrations and 1% , 3rd time: 2,5-dimercapto-1,3,4-thiadiazole derivative 2–0.06%, and 2,5-dimercapto-1,3,4-thiadiazole dimer 2–0.06%
(lower concentrations were not tested).

EXAMINATIONS
- Grading/Scoring system: - No reaction / ? Doubtful response, barely perceptible erythema / + Definite erythema, No edema / ++ Definite erythema, Definite edema / +++ Definite erythema, Definite edema & vesiculation

Results and discussion

Results of examinations:
NO. OF PERSONS WITH/OUT ALLERGIC REACTIONS:
- Number of subjects with positive reactions: 2
- Number of subjects with negative reactions: 110

Applicant's summary and conclusion

Conclusions:
Based on this case study it can be assumed that 1,3,4-Thiadiazole-2,5-dithiol possesses low potential to induce dermal sensitisation in human subjects.
Executive summary:

Patient 1: In 2001, in patch testing he reacted to guide-way oil at 20% (+?). 8 months later 3 components of the guide-way oil were tested, and the patient had an allergic reaction to 1 component of the guide-way oil, dimercaptothiadiazole (DMTD; trade name Oloa 4452X): 20% +, 10% ?+, 3.2% ?+, 1% ?+. 4 months later 2,5-Dimercapto-1,3,4-thiadiazole was tested for the second time: 2% +, 1%, 0.32%, and 0.1% mild follicular reaction (?+). 18 control patients were negative to 2% 2,5-dimercapto-1,3,4-thiadiazole.

Patient 2: In 2005 on patch testing he reacted to his centre lubrication grease (as such; ++) and 2,5-dimercapto-1,3,4- thiadiazole (1%, ++). 6 moths later, after many inquiries, the manufacturer of the centre grease informed us that it contained 0.25% 2,5-dimercapto- 1,3,4-thiadiazole (CAS 1072-71-5) derivative and 0.25% 5,5-dithiobis(1,3,4-thiadiazole-2(3H)-thione (CAS 72676-55-2; 2,5-dimercapto-1,3,4-thiadiazole dimer). In the meanwhile, we had tested the patient for the second time with the dilution series of the centre grease: 100–3.2% concentrations gave ++ reactions, and 1% gave a + reaction. 5 control patients were negative to 100% and 10% centre grease. On the 3rd patch test session he had strong allergic reactions (++) to the 2,5- dimercapto-1,3,4-thiadiazole derivative 2–0.06%, and to 2,5-dimercapto-1,3,4-thiadiazole dimer 2–0.06% (lower concentrations were not tested).