Vol. 282, Issue 1, 192-200, 1997

DMPS-Arsenic Challenge Test. I: Increased Urinary Excretion of Monomethylarsonic Acid in Humans Given Dimercaptopropane Sulfonate¹

H. Vasken Aposhian, Alex Arroyo, Mariano E. Cebrian, Luz María Del Razo, Katherine M. Hurlbut, Richard C. Dart, Diego Gonzalez-Ramirez, Helmut Kreppel, Hernan Speisky, Allan Smith, Maria E. Gonsebatt, Patricia Ostrosky-Wegman and Mary M. Aposhian

Department of Molecular and Cellular Biology, Life Sciences South Building, The University of Arizona, Tucson, Arizona (H.V.A., M.M.A.), Ministerio de Salud, Servicio de Salud Antofagasta, Antofagasta, Chile (A.A.), Seccion de Toxicologia Ambiental, CINVESTAV-IPN, Mexico, D.F. 07000, Mexico (M.E.C., L.M.D.R.), Rocky Mountain Poison and Drug Control Center, Denver, Colorado (K.M.H., R.C.D.), Department of Pharmacology, Centro Investigacion Biomedica del Noreste, IMSS, Monterrey, Mexico (D.G.R.), University of Munich, Walther Straub Institut für Pharmakologie und Toxikologie, Munich, Germany (H.K.), Biochemical Pharmacology Unit, INTA, Universidad de Chile, Santiago, Chile (H.S.), School of Public Health, University of California at Berkeley, Berkeley, California (A.S.) and Instituto de Investigaciones Biomédicas, UNAM, Circuito Escolar Interior Ciudad Universitaria, 04510 Mexico, DF.(M.E.G., P.O.W.)

The purpose of the present study was to evaluate in a novel manner the arsenic exposure of humans living in two towns in Northeastern Chile. Residents of one town drink water containing 593 µg As/l. Those in the control town drink water containing 21 µg As/l. Our hypothesis was that the administration of the chelating agent, 2,3-dimercaptopropane-1-sulfonic acid, Na salt (DMPS, DIMAVAL) would increase the urinary excretion of arsenic, alter the urinary profile of arsenic species and thus result in a better indication of the body load of arsenic and a better biomarker for arsenic exposure. The method used to evaluate these subjects was to give them 300 mg DMPS by mouth, after an overnight fast, and collect urine at specified time periods. The urine samples were analyzed for inorganic arsenic, monomethylarsonic acid (MMA), dimethylarsinic acid (DMA) and total arsenic by hydride generation and atomic absorption spectrophotometry. The results indicated that: 1) During the 2-hr period after DMPS administration, MMA represented 42%, inorganic As, 20 to 22% and DMA, 37 to 38% of the total urinary arsenic. The usual range of the MMA percentage in human urine has been 10 to 20%. The % MMA increased almost equally for both the arsenic-exposed and control subjects. 2) The exposed subjects had a greater urinary excretion of total arsenic, before and after DMPS administration, than the control subjects. 3) Although buccal cells were obtained only from a few subjects, the prevalence of mononucleated buccal cells, an indication of genotoxicity, was 5-fold greater for those who consumed drinking water with the higher arsenic content than among control subjects. Our conclusions are that 1) DMPS has a highly specific effect in humans on MMA metabolism and/or urinary excretion; 2) the human body stores substantial amounts of arsenic; and 3) the urinary arsenic concentration after DMPS administration may be more indicative of the body burden of arsenic because it was greater than that found before DMPS was given.