Pyridoxylamine reactivity kinetics as an amine based nucleophile for screening electrophilic dermal sensitizers.
Toxicology
; 315: 102-9, 2014 Jan 06.
Article
en En
| MEDLINE
| ID: mdl-24333919
ABSTRACT
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 × 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.
Palabras clave
AA; ACD; LLNA; Local lymph node assay; MA; Michael acceptor; NBT; Nucleophilic Substitution (1 or 2); Nucleophilic Substitution (aromatic); PDA; Pyridoxylamine; Reactivity assay; S(N)1/S(N)2; S(N)Ar; SBF; Schiff Base Formers; Skin sensitization; acylating agents; allergic contact dermatitis; local lymph node assay; nitrobenzenethiol; pyridoxylamine
Texto completo:
1
Colección:
01-internacional
Base de datos:
MEDLINE
Asunto principal:
Piridoxamina
/
Quinonas
/
Alérgenos
/
Aldehídos
/
Anhídridos
Tipo de estudio:
Diagnostic_studies
/
Etiology_studies
/
Screening_studies
Idioma:
En
Revista:
Toxicology
Año:
2014
Tipo del documento:
Article
País de afiliación:
Estados Unidos