## 2 Population and Methods
### Metal Analyses  
Samples were blinded and randomly distributed to the laboratory. We measured urinary (As, Ba, Be, Cd, Co, Cu, Hg, Li, Mo, Pb, Se, Sr, Tl, V, W and Zn), and toenail (same plus Al, Cr, Fe, Mn, Ni and U) levels. Determination of levels of metals in toenails and urine was carried out by the Department of Analytical Chemistry of the University of Huelva, using the recommendations established by the International Atomic Energy Agency [45].  
Urine samples were collected in urine collection polypropylene containers, which had been previously washed with nitric acid. Samples were frozen within 1-2 h of collection and stored at \(-80\)\({}^{\circ}\)C until analysis after being blinded and randomized. Trace metals in urine were analyzed by inductively coupled plasma mass spectrometry (ICP-MS) with dynamic reaction cell after diluting 1 mL of the sample five times with a 5% (\(\upsilon\)/\(\upsilon\)) solution of ultrapure nitric acid in ultrapure water and filtering through a 0.45 \(\upmu\)m polytetrafluoroethylene (PTFE) membrane filter before analysis. Quality control of the analysis was based on the following operations: (a) analysis of two reference materials, Clincheck (RECIPE) urine control for trace elements--level I and Standard Reference Material (2670a)--toxic elements in freeze-dried urine (LGC)--high level, in each sample batch, with a mean accuracy of 90% maintained \(\pm\)5%; (b) monitoring of the ICP-MS response during the time period by measurement of metal concentrations at a point on the calibration curve (2 ng mL\({}^{-1}\)), with every 20 samples analyzed, which guaranteed a good evaluation of the instrument response; (c) instrumental drift correction by addition of Rh (100 ng mL\({}^{-1}\)) as an internal standard to all the samples and calibrants, with the samples whose response differed \(\pm\) 10% with respect to the internal standard measured again; (d) analysis of every 5 samples of reagent blanks containing 5% (\(\upsilon\)/\(\upsilon\)) HNO\({}_{3}\) (Suprapur quality), 1% (\(\upsilon\)/\(\upsilon\)) HCl and Rh 100 ng mL\({}^{-1}\) in Milli-Q water; (e) analysis of duplicate samples every 2.5 h of the sequence; and (f) spiked sample analysis, by spiking the reference materials with the analytes under study (50 ng mL\({}^{-1}\)). Finally, potential interferences from molybdenum and tin, frequently present in urine, were removed by operating the ICP-MS system in helium collision mode (He flow: 4 mL min\({}^{-1}\)). The creatinine concentration in urine was determined by the classic Jaffe method.  
Toenail samples (50 to 100 mg) were first cleaned twice using 2 mL of a 5% (weight/volume) Triton water solution, then twice with 2 mL of Milli-Q water and finally twice with 2 mL of acetone with additional ultrasound treatment for 5 min. Then, samples were air dried and digested with 800 \(\upmu\)L of a (4:1) mixture of HNO\({}_{3}\) and H\({}_{2}\)O\({}_{2}\) of ultra trace metals grade quality, in a Teflon reactor for microwave-assisted attack. Mineralization was performed at 400 W, starting from room temperature, ramped up to 160 \({}^{\circ}\)C for 15 min and held for 20 min at this temperature. Finally, the extracts were filtered through a 0.45 \(\upmu\)m polytetrafluoroethylene (PTFE) membrane filter before analysis.  
Analyses of nail extract were performed by ICP-MS, similarly to those described for urine samples. In this case, 100 mg of human hair was used as the reference material (NSC DC73347a) in order to correct the instrumental variability, following a quality control procedure similar to that used in urine analysis.