Quantitation of biomarkers of exposure to nitrogen mustards in urine from rats dosed with nitrogen mustards and from an unexposed human population.
The nitrogen mustards bis(2-chloroethyl)ethylamine (HN1), bis(2-chloroethyl)methylamine (HN2), and tris(2-chloroethyl)amine (HN3) have the potential to be used as chemical terrorism agents because of their extreme vesicant properties. We modified a previously reported method to incorporate automated solid-phase extraction, improve chromatography, and include the urinary metabolite for HN3. The improved method was used to measure levels of the urinary metabolites N-ethyldiethanolamine (EDEA), N-methyldiethanolamine (MDEA), and triethanolamine (TEA) in rats dosed with HN1, HN2, and HN3, respectively, and to establish background levels of EDEA, MDEA, and TEA in human urine samples from a population with no known exposure to nitrogen mustards. Rat dosing experiments confirmed that EDEA, MDEA, and TEA could be detected in urine for at least 48 h after exposure to HN1, HN2, and HN3, respectively. Substantial amounts of EDEA (89 ng/mL), MDEA (170 ng/mL), and TEA (1105 ng/mL) were measured in the urine of rats exposed to 10 mg HN1, HN2, and HN3, respectively, 48 h after exposure. The background concentrations for TEA in the human population ranged from below the limit of detection (LOD 3 ng/mL) to approximately 6500 ng/mL. Neither EDEA (LOD 0.4 ng/mL) nor MDEA (LOD 0.8 ng/mL) was detected above the LOD in the human samples.
Lemire
Sharon W
SW
Division of Laboratory Sciences, National Center for Environmental Health, Centers for Disease Control and Prevention, Atlanta, Georgia 30341-3724, USA. SGL4@CDC.GOV
Barr
John R
JR
Ashley
David L
DL
Olson
Carl T
CT
Hayes
Timothy L
TL
D000279:Administration, Cutaneous; D000818:Animals; D015415:Biomarkers / Q000652:urine; D002619:Chemical Warfare Agents / Q000032:analysis / Q000493:pharmacokinetics* / Q000506:poisoning; D002851:Chromatography, High Pressure Liquid; D004781:Environmental Exposure / Q000032:analysis; D006801:Humans; D008297:Male; D008466:Mechlorethamine / Q000032:analysis / Q000493:pharmacokinetics* / Q000506:poisoning; D051381:Rats; D017208:Rats, Wistar; D012016:Reference Values; D021241:Spectrometry, Mass, Electrospray Ionization; D016482:Urinalysis
D015415:Biomarkers; D002619:Chemical Warfare Agents; D008466:Mechlorethamine