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Olga L. Valenzuela,¹ Victor H. Borja-Aburto,² Gonzalo G. Garcia-Vargas,³ Martha B. Cruz-Gonzalez,⁴ Eliud A. Garcia-Montalvo,¹ Emma S. Calderon-Aranda,¹ and Luz M. Del Razo¹

¹Seccion de Toxicología, Cinvestav-IPN, México DF, México; ²Salud en el Trabajo, Instituto Mexicano del Seguro Social, México DF, México; ³Facultad de Medicina, Universidad Juárez del Estado de Durango, Gómez Palacio, Durango, México; ⁴Servicios de Salud del Estado de Hidalgo, Pachuca, México

Abstract
Chronic exposure to inorganic arsenic (iAs) has been associated with increased risk of various forms of cancer and of noncancerous diseases. Metabolic conversions of iAs that yield highly toxic and genotoxic methylarsonite (MAs^III) and dimethylarsinite (DMAs^III) may play a significant role in determining the extent and character of toxic and cancer-promoting effects of iAs exposure. In this study we examined the relationship between urinary profiles of MAs^III and DMAs^III and skin lesion markers of iAs toxicity in individuals exposed to iAs in drinking water. The study subjects were recruited among the residents of an endemic region of central Mexico. Drinking-water reservoirs in this region are heavily contaminated with iAs. Previous studies carried out in the local populations have found an increased incidence of pathologies, primarily skin lesions, that are characteristic of arseniasis. The goal of this study was to investigate the urinary profiles for the trivalent and pentavalent As metabolites in both high- and low-iAs-exposed subjects. Notably, methylated trivalent arsenicals were detected in 98% of analyzed urine samples. On average, the major metabolite, DMAs^III, represented 49% of total urinary As, followed by DMAs^V (23.7%) , iAs^V (8.6%) , iAs^III (8.5%) , MAs^III (7.4%) , and MAs^V (2.8%) . More important, the average MAs^III concentration was significantly higher in the urine of exposed individuals with skin lesions compared with those who drank iAs-contaminated water but had no skin lesions. These data suggest that urinary levels of MAs^III, the most toxic species among identified metabolites of iAs, may serve as an indicator to identify individuals with increased susceptibility to toxic and cancer-promoting effects of arseniasis. Key words: arsenic, arsenic skin lesions, arsenic speciation, hyperkeratosis, hyperpigmentation, hypopigmentation, metabolism, methylation, trivalent arsenic, trivalent methylarsenic species, urine metabolites. Environ Health Perspect 113:250-254 (2005) . doi:10.1289/ehp.7519 available via http://dx.doi.org/ [Online 22 November 2004]

Address correspondence to L.M. Del Razo, Sección de Toxicología, Cinvestav-IPN, P.O. Box 14-740, Avenida Instituto Politécnico Nacional #2508, Colonia Zacatenco, CP 07300 México DF, México. Telephone: 52-55-5061-3307. Fax: 52-55-5747-7111. E-mail: ldelrazo@cinvestav.mx

We greatly appreciate the help of Coordinación de Investigación, Servicios de Salud de Hidalgo, and personnel from Centro de Salud de la Jurisdicción de Zimapan for coordinating the fieldwork. We thank D.J. Thomas (U.S. Environmental Protection Agency) for provision of custom-synthesized methylated trivalent arsenicals.

This study was supported by the Mexican Council for Science and Technology (Conacyt 38471-M) .

The authors declare they have no competing financial interests.

Received 23 August 2004 ; accepted 22 November 2004.