Globin s-propyl cysteine and urinary N-acetyl-S-propylcysteine as internal biomarkers of 1-bromopropane exposure.

1-Bromopropane (1-BP), an alternative to ozone-depleting solvents, is a neuro and reproductive toxicant in animals and humans. In this study, the dose responses for urinary AcPrCys and S-propylcysteine (PrCys) adducts on globin and neurofilaments were determined as a function of 1-BP exposure level and duration in the rat; and globin PrCys adducts and urinary AcPrCys were quantified in samples obtained from workers in a 1-BP production facility. Rats were exposed to 1-BP by inhalation for 2 weeks at 0, 50, 200, or 800 ppm and to 1-BP at 0 or 50 ppm for 4 weeks. After the 4-week exposures ended, half of the animals were euthanized immediately and half euthanized 8 days later. Urinary AcPrCys was measured using liquid chromatography-tandem mass spectrometry (LC/MS/MS) and gas chromatograph-mass spectrometry (GC/MS); and PrCys adducts were determined on globin and neurofilaments using LC/MS/MS. In rats, PrCys adduct and urinary AcPrCys levels demonstrated a linear dose response relative to exposure level. PrCys globin adducts demonstrated a linear cumulative dose response over the 4-week exposure period. Elimination of AcPrCys appeared biphasic with detectable levels still present in urine up to 8 days postexposure. A significant increase in globin PrCys adducts was observed in the 1-BP workers relative to control workers; and urinary AcPrCys increased with increasing 1-BP ambient exposure levels. The results of these studies demonstrate the ability of 1-BP to covalently modify proteins in vivo and support the potential of urinary AcPrCys and globin PrCys adducts to serve as biomarkers of 1-BP exposure in humans.