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.
Valentine
Holly
H
Department of Pathology, Vanderbilt University Medical Center, Nashville, Tennessee 37232-2561, USA. holly.valentine@vanderbilt.edu
Amarnath
Kalyani
K
Amarnath
Venkataraman
V
Li
Weihua
W
Ding
Xuncheng
X
Valentine
William M
WM
Ichihara
Gaku
G
D000111:Acetylcysteine / Q000031:analogs & derivatives* / Q000652:urine; D000395:Air Pollutants, Occupational / Q000633:toxicity; D000818:Animals; D015415:Biomarkers / Q000378:metabolism; D003545:Cysteine / Q000031:analogs & derivatives* / Q000378:metabolism; D004784:Environmental Monitoring; D005260:Female; D005914:Globins / Q000378:metabolism*; D006801:Humans; D006842:Hydrocarbons, Brominated / Q000633:toxicity; D019570:Inhalation Exposure; D008297:Male; D016273:Occupational Exposure; D011485:Protein Binding; D051381:Rats; D017208:Rats, Wistar; D012997:Solvents / Q000633:toxicity*
D000395:Air Pollutants, Occupational; D015415:Biomarkers; D006842:Hydrocarbons, Brominated; C520626:N-acetyl-S-propylcysteine; D012997:Solvents; C028742:S-propylcysteine; D005914:Globins; D003545:Cysteine; D000111:Acetylcysteine; C118559:1-bromopropane