Zinc diethyldithiocarbamate allergenicity: potential haptenation mechanisms [2008-02].

Details

• Personal Author:
  Chipinda I ; Hettick JM ; Siegel, Paul D. ; Simoyi RH
• Description:
  Background: Zinc diethyldithiocarbamate (ZDEC) and its disulfide, tetraethylthiuram disulfide (TETD), are rubber accelerators and contact allergens that cross-react in some individuals. Objective: This study explored potential protein haptenation mechanisms of ZDEC and its oxidation products. Methods: ZDEC oxidation/reduction products and sites of protein binding were assessed using high-performance liquid chromatography and mass spectrometry. The murine local lymph node assay (LLNA) was employed to probe haptenation mechanisms of ZDEC by examining its allergenicity along with its oxidation products and through elimination of oxidation and chelation mechanisms by substituting cobalt for zinc [cobalt (II) dithiocarbamate, CoDEC]. Results: Oxidation of ZDEC by hypochlorous acid (bleach, HOCl), iodine, or hydrogen peroxide resulted in production of TETD, tetraethylthiocarbamoyl disulfide, and tetraethyldicarbamoyl disulfide (TEDCD). Albumin thiols reduced TETD with subsequent mixed disulfide formation/haptenation. ZDEC directly chelated the copper ion on the active site of the superoxide dismutase, whereas CoDEC did not bind to Cu proteins or form mixed disulfides with free thiols. ZDEC, sodium diethyldithiocarbamate, TEDCD, and TETD were all positive in the LLNA except CoDEC, which was non-allergenic. Conclusion: The thiol is the critical functional group in ZDEC's allergenicity, and haptenation is predominantly through chelation of metalloproteins and formation of mixed disulfides. [Description provided by NIOSH]
• Subjects:
  Chelating Agents Chemistry Hypersensitivity Metals Occupational Health Oxidants Safety Skin Skin Absorption
• Keywords:
  Metallic-minerals; Skin-absorption; Skin-exposure; Skin-irritants; Skin-sensitivity; Chemical-hypersensitivity; Chemical-properties; Chelating-agents; Oxidation; Oxidative-metabolism; Oxidative-processes; Oxidative-enzymes
• ISSN:
  0105-1873
• Document Type:
  Text
• Genre:
  Journal Article
• Place as Subject:
  Oregon ; OSHA Region 10 ; OSHA Region 3 ; West Virginia
• CIO:
  National Institute for Occupational Safety and Health (NIOSH)
• Division:
  HELD - Health Effects Laboratory Division
• Topic:
  Workplace Safety & Health
• Location:
  North America
• Pages in Document:
  79-89
• Volume:
  59
• Issue:
  2
• NIOSHTIC Number:
  nn:20034303
• Citation:
  Contact Dermatitis 2008 Feb; 59(2):79-89
• Contact Point Address:
  Itai Chipinda, Allergy and Clinical Immunology Branch, Health Effects Laboratory Division, National Institute for Occupational Safety and Health, 1095 Willowdale Road, Morgantown, WV 26505-2888
• Email:
  ichipinda@cdc.gov
• Federal Fiscal Year:
  2008
• NORA Priority Area:
  Healthcare and Social Assistance ; Services
• Peer Reviewed:
  True
• Source Full Name:
  Contact Dermatitis
• Collection(s):
  National Institute for Occupational Safety and Health
• Main Document Checksum:
  urn:sha-512:84a954743916cd9f07c2f8d1538b381e65a17812823c6dd42bb6607195a687cf080d6ce8dd45fd99ae2c36702d7c95cb00e44e424383e8cb177f2c883598dfdd
• Download URL:
  https://stacks.cdc.gov/view/cdc/249186/cdc_249186_DS1.pdf
• File Type:
  [PDF - 381.70 KB ]