Zinc diethyldithiocarbamate allergenicity: potential haptenation mechanisms [2008-03].

Details

• Personal Author:
  Chipinda I ; Hettick JM ; Siegel, Paul D. ; Simoyi RH
• Description:
  Zinc diethyldithiocarbamate (ZDEC) and its disulfide, tetraethylthiuram disulfide (TETD) are rubber accelerant contact allergens that cross-react in some individuals. Rubber gloves are often worn while using oxidizing disinfectants. The present study explored potential protein haptenation mechanisms of ZDEC and its oxidation products. Oxidation of ZDEC by bleach, iodine or hydrogen peroxide resulted in production of TETD, tetraethylthiocarbamoyl disulfide (TETCD) and tetraethyldicarbamoyl disulfide (TEDCD). Cysteine, glutathione and albumin thiols reduced TETD with subsequent mixed disulfide formation suggesting a potential route of protein haptenation. Chelation of the copper ion bound on the active site of the monomeric Cu/Zn superoxide dismutase (SOD) by diethyldithiocarbamate was observed when ZDEC was reacted with SOD. The specificity of the ZDEC-Cu(II) reaction and lack of ZDEC reactivity with reduced Cys6 and Cys111 on SOD suggested formation of the DEC-Cu(II) co-ordinate bond as another haptenation mechanism. The murine local lymph node assay (LLNA) was used to evaluate sensitization potential of ZDEC, Cobalt-DEC (CoDEC), TETD and TEDCD. The ranking of the sensitization potency was ZDEC >or= TEDCD > TETD >> CoDEC (no sensitization achieved) with EC3 values 1.01, 1.70, 5.42 and >7.5 respectively. CoDEC does not bind to Cu-proteins or form mixed disulfides with free thiols demonstrating the importance of these properties in ZDEC sensitization. Paradoxically, oxidative substitution of S by O on the thiocarbamates of TETD (= TEDCD) was allergenic, but was not subject to haptenation through mixed disulfides or metal chelation. It is concluded that ZDEC may haptenize proteins through (1) chelation of metals on metalloproteins, (2) TETD mediated formation of mixed disulfides, and (3) possibly through nucleophilic addition onto an TEDCD electrophilic carbamoyl group. [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:
  1096-6080
• Document Type:
  Text
• Genre:
  Abstract or Summary
• Place as Subject:
  Oregon ; OSHA Region 10 ; OSHA Region 3 ; Washington ; 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:
  270-271
• Volume:
  102
• Issue:
  1
• NIOSHTIC Number:
  nn:20033607
• Citation:
  Toxicologist 2008 Mar; 102(1):270-271
• Federal Fiscal Year:
  2008
• NORA Priority Area:
  Healthcare and Social Assistance ; Services
• Peer Reviewed:
  False
• Source Full Name:
  The Toxicologist. Society of Toxicology 47th Annual Meeting and ToxExpo, March 16-20, 2008, Seattle, Washington
• Collection(s):
  National Institute for Occupational Safety and Health
• Main Document Checksum:
  urn:sha-512:7a16c4157f8f236c7288ffce3f2d90b3c0c1f523a373143e1f07eb18d948d9cc1782abe2aaebcbab08d21f5506e5cdbfc4f2b3065ac6012323c96a10c31a1a1f
• Download URL:
  https://stacks.cdc.gov/view/cdc/249180/cdc_249180_DS1.pdf
• File Type:
  [PDF - 7.83 MB ]