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Toxicological information

Sensitisation data (human)

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Administrative data

Endpoint:
sensitisation data (humans)
Type of information:
experimental study
Adequacy of study:
key study
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
other: Study well documented, meets generally accepted scientific principles, acceptable for assessment.

Data source

Reference
Reference Type:
publication
Title:
Sensitization to thiourea derivatives among Finnish patients with suspected contact dermatitis.
Author:
Liippo J, Ackermann L, Hasan T, Laukkanan A, Rantanen T, and Lammintausta K.
Year:
2010
Bibliographic source:
Contact dermatitis 63, 37-41

Materials and methods

Type of sensitisation studied:
skin
Study type:
other: patch test
Test guideline
Qualifier:
no guideline followed
Principles of method if other than guideline:
The aim of this study was to collect information on the occurrence of thiourea-related contact allergy and to show novel sources of sensitization.
GLP compliance:
no

Test material

Reference
Name:
Unnamed
Type:
Constituent
Type:
Constituent
Details on test material:
no data

Method

Type of population:
general
Ethical approval:
confirmed, but no further information available
Subjects:
15100 Finnish general dermatology patients with suspected contact allergy during a 6-year period.
Route of administration:
dermal
Details on study design:
Patients were patch tested with the Finnish baseline series (Chemotechnique Diagnostics, Vellinge, Sweden) and a thiourea mixture
in five central hospital dermatology clinics since 2002. The mixture of the three thiourea chemicals consisted of 0.5% (wt/wt) DETU, 0.5% DBTU, and 0.5% DPTU in petrolatum (pet.). In all, 1500 patients with suspected allergy to rubber compounds were further tested with the rubber chemical series
(Chemotechnique Diagnostics) containing DETU (1.0%, pet.), DBTU (1.0%, pet.), and DPTU (1.0%, pet.) among other rubber additives.
Patch test products were applied onto the upper back in Finn Chambers® (Epitest Ltd Oy, Tuusula, Finland) on Scanpor® tape (Norgesplaster A/S, Vennesla, Norway), removed after 2 days, and interpreted 1–3 days after the removal according to the International Contact Dermatitis Research Group criteria.

Results and discussion

Results of examinations:
Patch test reactions to the mixture and to DETU, DPTU, and DBTU A positive patch test reaction to the thiourea mixture was seen in 59 patients (0.39%). These patients included 30 females and 29 males, aged 52.6 and 42.1 years (mean), respectively. A majority (35/59) of the reactions were 2+ or more, and one, initially interpreted as a doubtful reaction, was eventually regarded as an allergic one because DETU yielded a 2+ reaction. The series of the rubber chemicals was tested in 33/59 patients (56%) . DPTU reactions were seen in 5/33 patients (15%).
Four patients reacted to the thiourea mixture but had negative results for the individual thioureas in the rubber chemical series. One of these patients had no other patch test reactions, whereas all the other three reacted to thiuram chemicals.

Applicant's summary and conclusion

Conclusions:
According this study, DPTU is a skin sensitizer in human.
Executive summary:

Background: Thiourea derivatives in rubber products may induce contact sensitization and allergic contact dermatitis. Sensitization is most often from neoprene rubber, but the multitude of possible sensitizing products has remained poorly characterized.

Objective: The aim of this study was to collect information on the occurrence of thiourea-related contact allergy and to show novel sources of sensitization.

Patients and methods: A mixture of dibutyl-, diethyl-, and diphenylthiourea was included in patch test baseline series in five Finnish dermatology clinics during 2002–2007. In addition, an extended series of rubber chemicals was tested in patients with suspected rubber allergy. Sources of sensitization to thioureas were analysed in sensitized patients.

Results: Thiourea mix yielded positive patch test reactions in 59 of 15 100 patients (0.39%); 33/59 patients were also tested with individual rubber chemicals. Diethylthiourea was positive in 24/33, diphenylthiourea in 5, and dibutylthiourea in 1 patient. The most common sources of sensitization

included various neoprene-containing orthopaedic braces, sports equipment, and foot wear.

Conclusions: The sources of sensitization to thiourea chemicals were detected in most cases. These sources comprise a heterogenous group of products extending from orthopaedic materials to sports equipment.