title: Isothiocyanates are important as haptens in contact allergy to chloroprene rubber.
abstract: BACKGROUND
  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.
  
  
  OBJECTIVE
  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.
  
  
  METHODS
  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.
  
  
  RESULTS
  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-2. At 35 °C, ethyl isothiocyanate was emitted from all samples. Patch-test preparations of diethylthiourea, diphenylthiourea and dibutylthiourea all emitted the corresponding isothiocyanate, with diethylthiourea showing the highest rate of isothiocyanate emission.
  
  
  CONCLUSIONS
  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.
authors.affiliation: Department of Environmental Science and Analytical Chemistry, Stockholm University, Svante Arrhenius väg 16, Stockholm, SE-106 91, Sweden.
authors.forename: A G
authors.initials: AG
authors.lastname: Ramzy
authors.affiliation: Department of Dermatology, Turku University Hospital, Turku, 20521, Finland.
authors.forename: K
authors.initials: K
authors.lastname: Lammintausta
authors.affiliation: Centre for Occupational and Environmental Medicine, Stockholm County Council and Institute of Environmental Medicine, Karolinska Institutet, Stockholm, 171 77, Sweden.
authors.forename: M
authors.initials: M
authors.lastname: Matura
authors.affiliation: Department of Dermatology, Sahlgrenska Academy at University of Gothenburg, Gothenburg, 413 45, Sweden.|Dermatochemistry, Department of Chemistry and Molecular Biology, University of Gothenburg, Gothenburg, 412 96, Sweden.
authors.forename: J
authors.initials: J
authors.lastname: Bråred Christensson
authors.affiliation: Department of Environmental Science and Analytical Chemistry, Stockholm University, Svante Arrhenius väg 16, Stockholm, SE-106 91, Sweden.
authors.forename: U
authors.initials: U
authors.lastname: Nilsson
authors.affiliation: Department of Dermatology, Sahlgrenska Academy at University of Gothenburg, Gothenburg, 413 45, Sweden.
authors.forename: L
authors.identifier: http://orcid.org/0000-0002-9141-9215
authors.initials: L
authors.lastname: Hagvall
mesh_terms: D000328:Adult; D002737:Chloroprene / Q000009:adverse effects* / Q000737:chemistry; D017449:Dermatitis, Allergic Contact / Q000209:etiology*; D005260:Female; D006241:Haptens / Q000009:adverse effects; D006801:Humans; D017953:Isocyanates / Q000009:adverse effects; D017879:Isothiocyanates / Q000009:adverse effects*; D008297:Male; D008875:Middle Aged; D010328:Patch Tests; D012408:Rubber / Q000009:adverse effects* / Q000737:chemistry; D013890:Thiourea / Q000009:adverse effects / Q000031:analogs & derivatives / Q000032:analysis
chemical_list: D006241:Haptens; D017953:Isocyanates; D017879:Isothiocyanates; D002737:Chloroprene; C035318:diethylthiourea; C034546:1,3-dibutyl-2-thiourea; D012408:Rubber; C032788:diphenylthiourea; D013890:Thiourea