Pyridoxylamine reactivity kinetics as an amine-based probe for screening electrophilic contact allergens

Details

• Personal Author:
  Chipinda I ; Mbiya W ; Siegel, Paul D. ; Simoyi RH
• Description:
  Covalent protein binding is an initial step in dermal contact sensitization. We previously reported the utility of a nitrobenzenethiol (NBT) binding assay for screening thiol reactive haptens (Chipinda et al Chem. Res. Tox. 2010). The present study describes an amine (pyridoxylamine (PDA)) absorbance and fluorescence-based reactivity kinetic probe to complement the NBT assay for identification of amine-selective haptens. Rate constants for 32 chemicals including 5 anhydrides, 6 aldehydes, 2 quinones, among other classes, were determined where reaction times to completion ranged from 20 s to > 2 h. Preliminary assessment suggests labile reactive intermediates are formed during PDA reaction to quinones and benzyl bromide. No reactivity was observed with some thiol-selective sensitizers such as propiolactone or nonsensitizers such as sulfanilamide and benzocaine. Strong correlation (R2 = 0.81) was obtained between PDA reactivity constant (pseudo-first order; k) and the local lymph node assay threshold (EC3) values. Reaction completion time of the sensitizers also correlated strongly (R2 = 0.74) with EC3 values suggesting utility of transforming this chemical reactivity method into a simple, inexpensive end-point assay. The results from the PDA method also highlight the utility of combining this amine based method with the previous NBT based model to be able to identify thiol selective, amine selective and non-selective electrophilic contact allergens. [Description provided by NIOSH]
• Subjects:
  Aldehydes Amines Anhydrides Antigens Biological Assay Formaldehyde Hypersensitivity Occupational Health Quinones Safety Skin Skin Absorption Sulfhydryl Compounds

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• Keywords:
  Allergens Binding-energy Bioassays Chemical-kinetics Dermatology Kinetics Lymph-nodes Proteins Reaction-rates Sensitization Skin-absorption Skin-exposure Skin-sensitivity Thiols

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• ISSN:
  1096-6080
• Document Type:
  Text
• Genre:
  Abstract or Summary
• Place as Subject:
  California ; Oregon ; OSHA Region 10 ; OSHA Region 3 ; OSHA Region 9 ; 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:
  126
• NIOSHTIC Number:
  nn:20040654
• Citation:
  Toxicologist 2012 Mar; 126(Suppl 1):565-566
• CAS Registry Number:
  Benzocaine (CAS RN 94-09-7) ; Benzyl bromide (CAS RN 100-39-0) ; beta-Propiolactone (CAS RN 57-57-8) ; Sulfanilamide (CAS RN 63-74-1)
• Federal Fiscal Year:
  2012
• NORA Priority Area:
  Healthcare and Social Assistance ; Services
• Peer Reviewed:
  False
• Source Full Name:
  The Toxicologist. Society of Toxicology 51st Annual Meeting and ToxExpo, March 11-15, 2012, San Francisco, California
• Supplement:
  1
• Collection(s):
  National Institute for Occupational Safety and Health
• Main Document Checksum:
  urn:sha-512:522dcd1078fedb48b61a0377694fcd8989b60bec1b9d69dcbecabd3f4eb58c2f91d1db0d470809cd99c16140ad9a85fd00063beb13b01a3e5de4cf46a1880d66
• Download URL:
  https://stacks.cdc.gov/view/cdc/193444/cdc_193444_DS1.pdf
• File Type:
  [PDF - 484.79 KB ]