Activation mechanism of Tris(2,3-dibromopropyl)phosphate to the potent mutagen, 2-bromoacrolein

Abstract The potent mutagen 2-bromoacrolein is formed from the carcinogenic flame retardant tris(2,3-dibromopropyl)phosphate (Tris-BP) on incubation with hepatic microsomes. Substitution of deuterium for hydrogen at the terminal carbon atoms (C-3) of Tris-BP significantly decreased both the mutagenic response and the formation rate of 2-bromoacrolein. Mass spectral analysis of the 2-bromoacrolein that was formed from the selectively deuterated analogs of Tris-BP revealed that the primary mechanism for the formation of 2-bromoacrolein involves an initial oxidative dehalogenation at C-3 followed by a β-elimination reaction.