Rapid and Simple Kinetics Screening Assay for Electrophilic Dermal Sensitizers Using Nitrobenzenethiol

Details

• Personal Author:
  Ajibola RO ; Chipinda I ; Morakinyo MK ; Ruwona TB ; Siegel, Paul D. ; Simoyi RH
• Description:
  The need for alternatives to animal-based skin sensitization testing has spurred research on the use of in vitro, in silico, and in chemico methods. Glutathione and other select peptides have been used to determine the reactivity of electrophilic allergens to nucleophiles, but these methods are inadequate to accurately measure rapid kinetics observed with many chemical sensitizers. A kinetic spectrophotometric assay involving the reactivity of electrophilic sensitizers to nitrobenzenethiol was evaluated. Stopped-flow techniques and conventional UV spectrophotometric measurements enabled the determination of reaction rates with half-lives ranging from 0.4 ms (benzoquinone) to 46.2 s (ethyl acrylate). Rate constants were measured for seven extreme, five strong, seven moderate, and four weak/nonsensitizers. Seventeen out of the 23 tested chemicals were pseudo-first order, and three were second order. In three out of the 23 chemicals, deviations from first and second order were apparent where the chemicals exhibited complex kinetics whose rates are mixed order. The reaction rates of the electrophiles correlated positively with their EC3 values within the same mechanistic domain. Nonsensitizers such as benzaldehyde, sodium lauryl sulfate, and benzocaine did not react with nitrobenzenethiol. Cyclic anhydrides, select diones, and aromatic aldehydes proved to be false negatives in this assay. The findings from this simple and rapid absorbance model show that for the same mechanistic domain, skin sensitization is driven mainly by electrophilic reactivity. This simple, rapid, and inexpensive absorbance-based method has great potential for use as a preliminary screening tool for skin allergens. [Description provided by NIOSH]
• Subjects:
  Chemistry Cytotoxins Environmental Monitoring Hazardous Substances Hypersensitivity Laboratories Occupational Health Safety Skin Skin Absorption Skin Diseases

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• Keywords:
  Allergic-dermatitis Allergic-reactions Allergies Biological-effects Cell-biology Cellular-reactions Chemical-analysis Chemical-hypersensitivity Chemical-properties Chemical-reactions Cytotoxic-effects Exposure-assessment Exposure-levels Exposure-methods Laboratory-animals Laboratory-testing Skin-absorption Skin-exposure Skin-irritants Skin-sensitivity Statistical-analysis Toxic-effects

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• ISSN:
  0893-228X
• Document Type:
  Text
• Genre:
  Journal Article
• Place as Subject:
  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
• Volume:
  23
• Issue:
  5
• NIOSHTIC Number:
  nn:20036876
• Citation:
  Chem Res Toxicol 2010 May; 23(5):918-925
• Contact Point Address:
  Itai Chipinda, Health Effects Laboratory Division, National Institute for Occupational Safety and Health, 1095 Willowdale Road, Morgantown, WV 26505-2888
• Email:
  IChipinda@cdc.gov
• CAS Registry Number:
  Glutathione (CAS RN 70-18-8)
• Federal Fiscal Year:
  2010
• NORA Priority Area:
  Services
• Peer Reviewed:
  True
• Source Full Name:
  Chemical Research in Toxicology
• Collection(s):
  National Institute for Occupational Safety and Health
• Main Document Checksum:
  urn:sha-512:1546cc1c7882b9aa98d575ea8f205b3d4382020b7f0328b49d48d65659e73a1a8a301de17a2f6e56578faae26cf41d7221162c72d1368e29380632d48c427242
• Download URL:
  https://stacks.cdc.gov/view/cdc/188116/cdc_188116_DS1.pdf
• File Type:
  [PDF - 792.25 KB ]