Zinc diethyldithiocarbamate allergenicity: potential haptenation mechanisms.
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.


CONCLUSIONS
The thiol is the critical functional group in ZDEC's allergenicity, and haptenation is predominantly through chelation of metalloproteins and formation of mixed disulfides.
Chipinda
Itai
I
Allergy and Clinical Immunology Branch, Health Effects Laboratory Division, National Institute for Occupational Safety and Health, Morgantown, WV 26505-2888, USA. ichipinda@cdc.gov
Hettick
Justin M
JM
Simoyi
Reuben H
RH
Siegel
Paul D
PD