PMID- 24333919
OWN - NLM
STAT- MEDLINE
DCOM- 20140303
LR  - 20211021
IS  - 1879-3185 (Electronic)
IS  - 0300-483X (Print)
IS  - 0300-483X (Linking)
VI  - 315
DP  - 2014 Jan 6
TI  - Pyridoxylamine reactivity kinetics as an amine based nucleophile for screening 
      electrophilic dermal sensitizers.
PG  - 102-9
LID - S0300-483X(13)00322-3 [pii]
LID - 10.1016/j.tox.2013.11.009 [doi]
AB  - Chemical allergens bind directly, or after metabolic or abiotic activation, to 
      endogenous proteins to become allergenic. Assessment of this initial binding has 
      been suggested as a target for development of assays to screen chemicals for 
      their allergenic potential. Recently we reported a nitrobenzenethiol (NBT) based 
      method for screening thiol reactive skin sensitizers, however, amine selective 
      sensitizers are not detected by this assay. In the present study we describe an 
      amine (pyridoxylamine (PDA)) based kinetic assay to complement the NBT assay for 
      identification of amine-selective and non-selective skin sensitizers. UV-Vis 
      spectrophotometry and fluorescence were used to measure PDA reactivity for 57 
      chemicals including anhydrides, aldehydes, and quinones where reaction rates 
      ranged from 116 to 6.2 x 10(-6) M(-1) s(-1) for extreme to weak sensitizers, 
      respectively. No reactivity towards PDA was observed with the thiol-selective 
      sensitizers, non-sensitizers and prohaptens. The PDA rate constants correlated 
      significantly with their respective murine local lymph node assay (LLNA) 
      threshold EC3 values (R(2) = 0.76). The use of PDA serves as a simple, 
      inexpensive amine based method that shows promise as a preliminary screening tool 
      for electrophilic, amine-selective skin sensitizers.
CI  - Copyright (c) 2013 Elsevier Ireland Ltd. All rights reserved.
FAU - Chipinda, Itai
AU  - Chipinda I
AD  - Health Effects Laboratory Division, National Institute for Occupational Safety 
      and Health, Morgantown, WV 26505-2888, United States.
FAU - Mbiya, Wilbes
AU  - Mbiya W
AD  - Department of Chemistry, Portland State University, Portland, OR 97207-0751, 
      United States.
FAU - Adigun, Risikat Ajibola
AU  - Adigun RA
AD  - Department of Chemistry, Portland State University, Portland, OR 97207-0751, 
      United States.
FAU - Morakinyo, Moshood K
AU  - Morakinyo MK
AD  - Department of Chemistry, Portland State University, Portland, OR 97207-0751, 
      United States.
FAU - Law, Brandon F
AU  - Law BF
AD  - Health Effects Laboratory Division, National Institute for Occupational Safety 
      and Health, Morgantown, WV 26505-2888, United States.
FAU - Simoyi, Reuben H
AU  - Simoyi RH
AD  - Department of Chemistry, Portland State University, Portland, OR 97207-0751, 
      United States.
FAU - Siegel, Paul D
AU  - Siegel PD
AD  - Health Effects Laboratory Division, National Institute for Occupational Safety 
      and Health, Morgantown, WV 26505-2888, United States. Electronic address: 
      pds3@cdc.gov.
LA  - eng
GR  - CC999999/Intramural CDC HHS/United States
GR  - Y01 ES000001/ES/NIEHS NIH HHS/United States
GR  - Y1-ES-0001-12/ES/NIEHS NIH HHS/United States
PT  - Journal Article
PT  - Research Support, N.I.H., Extramural
PT  - Research Support, U.S. Gov't, Non-P.H.S.
DEP - 20131212
PL  - Ireland
TA  - Toxicology
JT  - Toxicology
JID - 0361055
RN  - 0 (Aldehydes)
RN  - 0 (Allergens)
RN  - 0 (Anhydrides)
RN  - 0 (Quinones)
RN  - 6466NM3W93 (Pyridoxamine)
SB  - IM
MH  - Aldehydes/metabolism/*toxicity
MH  - Allergens/metabolism/*toxicity
MH  - Anhydrides/metabolism/*toxicity
MH  - Dermatitis, Allergic Contact/etiology/immunology
MH  - Local Lymph Node Assay
MH  - Pyridoxamine/*chemistry
MH  - Quinones/metabolism/*toxicity
MH  - Skin/immunology/metabolism
MH  - Spectrometry, Fluorescence
MH  - Spectrophotometry, Ultraviolet
PMC - PMC4593055
MID - NIHMS722302
OID - NLM: HHSPA722302
OTO - NOTNLM
OT  - AA
OT  - ACD
OT  - LLNA
OT  - Local lymph node assay
OT  - MA
OT  - Michael acceptor
OT  - NBT
OT  - Nucleophilic Substitution (1 or 2)
OT  - Nucleophilic Substitution (aromatic)
OT  - PDA
OT  - Pyridoxylamine
OT  - Reactivity assay
OT  - S(N)1/S(N)2
OT  - S(N)Ar
OT  - SBF
OT  - Schiff Base Formers
OT  - Skin sensitization
OT  - acylating agents
OT  - allergic contact dermatitis
OT  - local lymph node assay
OT  - nitrobenzenethiol
OT  - pyridoxylamine
COIS- Conflict of interest: The authors declare that there are no conflicts of 
      interests.
EDAT- 2013/12/18 06:00
MHDA- 2014/03/04 06:00
PMCR- 2015/10/05
CRDT- 2013/12/17 06:00
PHST- 2013/09/19 00:00 [received]
PHST- 2013/11/11 00:00 [revised]
PHST- 2013/11/25 00:00 [accepted]
PHST- 2013/12/17 06:00 [entrez]
PHST- 2013/12/18 06:00 [pubmed]
PHST- 2014/03/04 06:00 [medline]
PHST- 2015/10/05 00:00 [pmc-release]
AID - S0300-483X(13)00322-3 [pii]
AID - 10.1016/j.tox.2013.11.009 [doi]
PST - ppublish
SO  - Toxicology. 2014 Jan 6;315:102-9. doi: 10.1016/j.tox.2013.11.009. Epub 2013 Dec 
      12.