Environmental Research 106 (2008) 110–120 Gender and age differences in the metabolism of inorganic arsenic in a highly exposed population in Bangladesh Anna-Lena Lindberg a , Eva-Charlotte Ekstro¨m b , Barbro Nermell a , Mahfuzar Rahman c , Bo Lo¨nnerdal d , Lars-A ˚ ke Persson b , Marie Vahter a,Ã a Institute of Environmental Medicine, Karolinska Institutet, Stockholm, Sweden b International Maternal and Child Health, Uppsala University, Uppsala, Sweden c International Centre for Diarrhoeal Disease Research, Bangladesh (ICDDR,B), Dhaka, Bangladesh d Department of Nutrition, University of California, Davis, CA, USA Received 28 February 2007; received in revised form 16 August 2007; accepted 21 August 2007 Available online 27 September 2007 Abstract Although genetic polymorphisms have been shown to explain some of the large variation observed in the metabolism of inorganic arsenic there may be several other factors playing an important role, e.g. nutrition. The objective of this study was to elucidate the influence of various factors on current arsenic exposure and metabolism in Matlab, a rural area in Bangladesh, where elevated water arsenic concentrations and malnutrition are prevalent. In total 1571 individuals, randomly selected from all inhabitants above 5 years of age, were investigated by measuring arsenic in urine and drinking water. In a subset of 526 randomly selected individuals, arsenic metabolites were speciated using HPLC coupled to inductively coupled plasma mass spectrometry (HPLC-HG-ICPMS). A significant association was observed between arsenic in urine and drinking water (R 2 ¼ 0.41). The contribution to urinary arsenic from arsenic exposure from food and other water sources was calculated to be almost 50 mg/L. The individuals in the present study had remarkably efficient methylation, in spite of high exposure and prevalence of malnutrition. Gender and age were major factors influencing arsenic metabolism in this population with a median of 77 mg/L of arsenic in urine (range: 0.5–1994 mg/L). Women had higher arsenic methylation efficiency than men, but only in childbearing age, supporting an influence of sex hormones. Overall, exposure level of arsenic, gender and age explained at most 30% of the variation in the present study, indicating that genetic polymorphisms are the most important factor influencing the metabolism of inorganic arsenic. r 2007 Elsevier Inc. All rights reserved. Keywords: Inorganic arsenic; Methylation; Gender differences; Age differences; Urine 1. Introduction Elevated inorganic arsenic (iAs) concentrations in drinking water is a major concern world-wide, particularly in low-income countries (IARC, 2004). In Bangladesh alone it has been estimated that more than 50 of the country’s 130 million inhabitants are drinking water containing arsenic concentrations above maximum guide- line value of 10 mg/L recommended by the World Health Organization (WHO) (Chakraborti et al., 2004; WHO, 2003). Chronic exposure has been associated with several adverse health effects, e.g. different forms of cancer, skin lesions, vascular disease, liver- and neurotoxicity, chronic cough and diabetes mellitus (IARC, 2004; WHO, 2001). Inorganic arsenic is metabolized via reduction and methylation using one-carbon metabolism with S-adeno- sylmethionine (SAM) as methyl donor, and is excreted mainly in urine as dimethylarsinate (DMA(V)) and methylarsonate (MA(V)) (Vahter, 2002). Several studies have shown an increasing prevalence of arsenic-related toxic effects with increasing percentage of MA in urine (Chen et al., 2003a, b, 2005; Del Razo et al., 1997; Hsueh et al., 1997; Maki-Paakkanen et al., 1998; Pu et al., 2007; ARTICLE IN PRESS www.elsevier.com/locate/envres 0013-9351/$ - see front matter r 2007 Elsevier Inc. All rights reserved. doi:10.1016/j.envres.2007.08.011 Ã Corresponding author. Division of Metals and Health, Institute of Environmental Medicine, Karolinska Institutet, Stockholm, Sweden. Fax: +46 8 33 69 81. E-mail address: Marie.Vahter@ki.se (M. Vahter).