diphenylthiourea and Dermatitis--Allergic-Contact

Contact allergy to chloroprene rubber products is well known. Thiourea compounds are considered the cause of allergy. Diethylthiourea commonly occurs in this type of product and can decompose to the sensitizer ethyl isothiocyanate.. To investigate the clinical importance of degradation products and metabolites from organic thioureas in contact allergy to chloroprene rubber with a focus on isothiocyanates and isocyanates.. Patients with contact allergy to diphenylthiourea were patch tested with phenyl isothiocyanate and phenyl isocyanate. Patients with known contact allergy to diethylthiourea were retested with diethylthiourea, while chemical analyses of their chloroprene rubber products were performed. The stability of diethylthiourea, diphenylthiourea and dibutylthiourea in patch-test preparations was investigated. Liquid chromatography/mass spectrometry and solid-phase microextraction/gas chromatography were used for determination of organic thioureas and isothiocyanates.. All patients allergic to diphenylthiourea reacted to phenyl isothiocyanate, two of eight reacted to phenyl isocyanate and six of eight reacted to diphenylthiourea. Four patients allergic to diethylthiourea reacted at retest; diethylthiourea was detected in all chloroprene rubber samples, with levels of 2-1200 nmol cm. Thiourea compounds are degraded to isothiocyanates, which are generally strong or extreme sensitizers, thus acting as prehaptens. This process occurs in both chloroprene rubber products and patch-test preparations. Positive reactions to phenyl isocyanate indicate cutaneous metabolism, as the only known source of exposure to phenyl isocyanate is through bioactivation of diphenylthiourea.

Topics: Adult; Chloroprene; Dermatitis, Allergic Contact; Female; Haptens; Humans; Isocyanates; Isothiocyanates; Male; Middle Aged; Patch Tests; Rubber; Thiourea

Exposure to chloroprene rubber has resulted in numerous cases of allergic contact dermatitis, attributed to organic thiourea compounds used as vulcanization accelerators. However, thiourea compounds are not considered to be strong haptens.. To analyse common commercial chloroprene materials for their contents of diethylthiourea (DETU), dibutylthiourea (DBTU), diphenylthiourea (DPTU), and their degradation products, isothiocyanates; and to investigate the sensitization potencies of possible degradation products of the mentioned thiourea compounds.. Liquid chromatography/mass spectrometry (MS) was used for quantification of organic thiourea compounds in chloroprene products, such as medical, sports and diving gear; isothiocyanates were measured by solid-phase microextraction/gas chromatography/MS. Sensitization potencies were determined with the murine local lymph node assay (LLNA).. DETU was identified at concentrations of 2.7-9.4 µg/cm(2) in all samples, whereas neither DBTU nor DPTU was detected. At 37°C, degradation of DETU in the materials to ethyl isothiocyanate (EITC) was detected. EITC and ethyl isocyanate showed extreme and strong sensitization potencies, respectively, in the LLNA.. DETU can act as a prehapten, being degraded to EITC when subjected to body temperature upon skin contact. EITC could thus be the culprit behind allergic contact dermatitis caused by chloroprene rubber.

Topics: Allergens; Dermatitis, Allergic Contact; Humans; Isothiocyanates; Local Lymph Node Assay; Neoprene; Thiourea

Diphenylthiourea (DPTU) is a known skin sensitizer commonly used as a vulcanization accelerator in the production of synthetic rubber, for example, neoprene. The versatile usage of neoprene is due to the multifaceted properties of the material; for example, it is stretchable, waterproof, and chemical- and abrasion-resistant. The wide application of neoprene has resulted in numerous case reports of dermatitis patients allergic to DPTU. The mechanism by which DPTU works as a contact allergen has not been described; thus, the aim of the present study was to investigate if DPTU is a prohapten that can be activated by skin metabolism. The metabolic activation and covalent binding of (14)C-labeled DPTU to proteins were tested using a skinlike cytochrome P450 (P450) cocktail containing the five most abundant P450s found in human skin (CYP1A1, 1B1, 2B6, 2E1, and 3A5) and human liver microsomes. The incubations were carried out in the presence or absence of the metabolite trapping agents glutathione, methoxylamine, and benzylamine. The metabolism mixtures were analyzed by LC-radiochromatography, LC-MS, and LC-MS/MS. DPTU was mainly metabolically activated to reactive sulfoxides resulting in desulfurated adducts in both enzymatic systems used. Also, phenylisothiocyanate and phenylisocyanate were found to be metabolites of DPTU. The sensitizing capacity of the substrate (DPTU) and three metabolites was tested in the murine local lymph node assay. Two out of three metabolites tested were strong skin sensitizers, whereas DPTU itself, as previously known, was negative using this mouse model. In conclusion, DPTU forms highly reactive metabolites upon bioactivation by enzymes present in the skin. These metabolites are able to induce skin sensitization and are probable causes for DPTU allergy. To increase the possibilities of diagnosing contact allergy to DPTU-containing items, we suggest that suitable metabolites of DPTU should be used for screening testing.

Topics: Animals; Benzylamines; Cytochrome P-450 Enzyme System; Dermatitis, Allergic Contact; Disease Models, Animal; Glutathione; Humans; Hydroxylamines; Isothiocyanates; Mice; Microsomes, Liver; Protein Binding; Rubber; Skin; Thiourea

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

Topics: Adolescent; Adult; Aged; Braces; Dermatitis, Allergic Contact; Female; Finland; Humans; Latex Hypersensitivity; Male; Middle Aged; Patch Tests; Rubber; Shoes; Sports Equipment; Thiourea; Young Adult

About 21% of the patients with occupational contact dermatitis registered in the Information Network of Departments of Dermatology (IVDK) in the years 1995-2001 were patch tested due to suspected rubber glove allergy. We analysed reaction frequencies to thiurams, dithiocarbamates, mercaptobenzothiazole (MBT) and its derivatives, thioureas, and 1,3-diphenylguanidine (1,3-DPG). Thiurams were by far the most frequent rubber allergens in these patients (16.2% positive reactions, age- and sex-standardized), and the reaction frequency showed a decline from 20.9% in 1997 to 12.8% in 2000. However, this trend was not statistically significant, and was followed by an increase to 16.5% in 2001. All other rubber allergens showed no time trend at all. Although, according to manufacturers' information, the use of dithiocarbamates and MBT derivatives in rubber glove production increased in recent years, these allergens elicited positive reactions in only about 3% of the patients tested, and showed no increasing trend. Thioureas and 1,3-DPG are not widely used in rubber glove production, and play only a minor role in rubber glove contact allergy. Most of the positive reactions to 1,3-DPG are probably false-positive, irritant reactions.

Topics: Adult; Allergens; Benzothiazoles; Dermatitis, Allergic Contact; Dermatitis, Occupational; Female; Germany; Gloves, Protective; Hand Dermatoses; Humans; Latex Hypersensitivity; Male; Thiazoles; Thiocarbamates; Thiourea; Thiram

Topics: Allergens; Butylated Hydroxytoluene; Dermatitis, Allergic Contact; Dermatitis, Occupational; Diagnosis, Differential; Humans; Male; Microcomputers; Middle Aged; Patch Tests; Thiourea; Thumb

Topics: Arthroplasty, Replacement, Hip; Dermatitis, Allergic Contact; Female; Humans; Middle Aged; Neoprene; Orthopedic Fixation Devices; Patch Tests; Phenylenediamines; Thiourea

Topics: Buttocks; Clothing; Dermatitis, Allergic Contact; Female; Humans; Middle Aged; Neoprene; Textiles; Thigh; Thiourea

Topics: Braces; Dermatitis, Allergic Contact; Humans; Male; Middle Aged; Neoprene; Thiourea

Topics: Adult; Dermatitis, Allergic Contact; Diving; Humans; Male; Neoprene; Thiourea