Variability of Metal Levels in Spot , First Morning , and 24-Hour Urine Samples over a 3-Month Period in Healthy Adult Chinese Men

Introduction Metals, including essential and nonessential elements, are naturally present in the environment at highly varying concentrations and are also widely used in industrial processes and human activities; humans can be exposed to metals either voluntarily through supplementation or involuntarily through intake of contaminated food and water and inhalation of ambient air pollution (Meeker et al. 2010). Consequently, detectable levels of metals have been reported in most human biological samples from numerous studies worldwide including in China [Centers for Disease Control and Prevention (CDC) 2014; Feng et al. 2015; Health Canada 2010; Kile et al. 2009; Smolders et al. 2014]. Toxic elements such as arsenic (As), cadmium (Cd), and lead (Pb) have been associated with impaired human semen quality and sperm DNA integrity at relatively low levels (Meeker et al. 2008; Telisman et al. 2007). Essential elements, such as cobalt (Co), copper (Cu), molybdenum (Mo), and nickel (Ni), are necessary for good health but have also been reported to be associated with changes to male reproductive health measures, such as reduced semen quality and altered serum levels of testosterone if above specific levels in animals and in humans (Danadevi et al. 2003; Lewis and Meeker 2015; Meeker et al. 2008; Pedigo et al. 1988). Measurements of metals in urine are frequently used as biomarkers in human investigations, especially in surveys involving a large number of participants, such as the National Health and Nutrition Examination Survey (NHANES) in the USA (CDC 2014) and the Canadian Health Measures Survey (CHMS) in Canada (Health Canada 2010). A spot urine sample is the most commonly used sample type because its collection is relatively simple and noninvasive. However, metals in spot samples are likely to vary over time because of the variable exposure driven by changes in diet, lifestyle, or the daily activities of a person (Barr et al. 2005; Smolders et al. 2014). That variation may be more pronounced for metals that are rapidly eliminated after external exposure. Correction for urinary dilution, such as creatinine-corrected concentrations, may introduce an additional source of variability that does not reflect urine dilution (Barr et al. 2005). Because most reproductive health end points of interest, such as sperm quality, are likely associated with metal exposures over time intervals of months, concerns have been raised as to whether single measurements of metals in spot urine samples accurately reflect individual exposure over time (Smolders et al. 2014). Several previous studies have examined the temporal variability in the urinary levels of As, Cd, and Ni. In a Bangladesh study, Kile et al. (2009) found fair to good reproducibility in urinary As concentrations but poor reproducibility in percent As species among 196 participants who provided repeated spot urine samples during a 2-year period. In a U.S. study conducted with 141 women, Gunier et al. (2013) revealed that Cd concentrations in repeated 24-hr urine samples were only fair to good reproducible over 3–9 months. A more recent study in Belgium collecting spot urine samples from 8 adults also reported poor reproducibility in urinary As and Ni concentrations over a 6-day period (Smolders et al. 2014). Differences in the source and extent of exposure (e.g., smoking status, water consumption, fish intake) may contribute to some of the differences among these studies. However, the variability patterns of metals in spot, first morning, and 24-hr urine samples obtained from the same person during a 3-month period, which corresponds to the duration of spermatogenesis, remain unclear. To address the data gap, we conducted this study in 11 men with the intention to a) assess the reproducibility of serial measurements of As, Cd, Co, Cu, Mo, Ni, and Pb in