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Zinc diethyldithiocarbamate allergenicity: potential haptenation mechanisms.

Authors
Chipinda-I; Hettick-JM; Simoyi-RH; Siegel-PD
Source
Contact Dermatitis 2008 Feb; 59(2):79-89
NIOSHTIC No.
20034303
Abstract
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.
Keywords
Metallic-minerals; Skin-absorption; Skin-exposure; Skin-irritants; Skin-sensitivity; Chemical-hypersensitivity; Chemical-properties; Chelating-agents; Oxidation; Oxidative-metabolism; Oxidative-processes; Oxidative-enzymes
Contact
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
CODEN
CODEDG
Publication Date
20080201
Document Type
Journal Article
Email Address
ichipinda@cdc.gov
Fiscal Year
2008
NTIS Accession No.
NTIS Price
Issue of Publication
2
ISSN
0105-1873
NIOSH Division
HELD
Priority Area
Healthcare and Social Assistance; Services
Source Name
Contact Dermatitis
State
WV; OR
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