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Hyperuricemia is becoming a serious public health issue, which is highly influenced by environmental factors, although there is still controversial information on the potential influence of the exposure to Persistent Toxic Substances (PTSs) in the general population. In this study we aimed to assess the association. PTS exposure with uric acid homeostasis in a sample of the Spanish population. Participants were recruited during 2009–2010 in all the main geographical areas of Spain. Exposure to 34 PTSs was estimated by chemical analyses of serum levels of 6 Polychlorinated Biphenyls (PCBs, n=950), 13 Organochlorine Pesticides (OCPs, n=453), 6 Perfluoroalkyl Substances (PFAs, n=755), 7 Polybrominated Diphenyl Ethers (PBDEs, n=365), urinary Cadmium (n=926), and Lead in whole blood (n=882). The two study outcomes were defined as the prevalence of hyperuricemia in the study population and uric acid levels, the latter only in individuals with no previous diagnosis of hyperuricemia. Statistical analyses were performed by means of binomial logistic regression and linear regression, and mixture effects were screened using Weighted Quantile Sum Regression (WQS). Serum concentrations of γ-HCH, o,p´-DDE, PCB-138, PCB-153, PFOA, and urinary Cadmium were associated with an increased risk of hyperuricemia, while PBDE-153 showed an inverse association with the effect. Furthermore, exposure to Cadmium, PCB-138, and to PCB-153 was positively associated with uric acid levels. Results were consistent after lipid adjustment or standardization. WQS analyses revealed a major contribution of PCB-153 within the PCB mixture on both the risk of hyperuricemia and uric acid levels. Sensitivity analyses were performed by adjusting for dietary habits, fasting glucose and estimated glomerular filtration rate. Overall, we found novel associations between human exposure to mixtures of PTSs and disturbances in uric acid homeostasis. However, we cannot completely rule out potential residual confounding effect or reversedcausality related to the cross-sectional design., This work was funded as part of a research agreement between the Ministerio de Agricultura, Alimentación y Medioambiente, Spain and the Instituto de Salud Carlos III, Madrid , Spain (Project N_ SEG 1251/ 07, 1210/10 and 1321/15).

This manuscript presents the levels of six indicator polychlorinated biphenyl (PCB) congeners (IUPAC nos. 28, 52, 101, 138, 153 and 180) in the serum of 1880 individuals from a representative sample of the Spanish working population recruited between March 2009 and July 2010. Three out of the six PCBs studied (180, 153 and 138) were quantified in more than 99% of participants. PCB 180 was the highest contributor, followed by PCBs 153 and 138, with relative abundances of 42.6%, 33.2% and 24.2%, respectively. In contrast, PCBs 28 and 52 were detected in only 1% of samples, whereas PCB 101 was detectable in 6% of samples. The geometric mean (GM) for ΣPCBs138/153/180 was 135.4 ng/g lipid (95% CI: 121.3-151.2 ng/g lipid) and the 95th percentile was 482.2 ng/g lipid. Men had higher PCB blood concentrations than women (GMs 138.9 and 129.9 ng/g lipid respectively). As expected, serum PCB levels increased with age and frequency of fish consumption, particularly in those participants younger than 30 years of age. The highest levels we found were for participants from the Basque Country, whereas the lowest concentrations were found for those from the Canary Islands. The Spanish population studied herein had similar levels to those found previously in Greece and southern Italy, lower levels than those in France and central Europe, and higher PCB levels than those in the USA, Canada and New Zealand. This paper provides the first baseline information regarding PCB exposure in the Spanish adult population on a national scale. The results will allow us to establish reference levels, follow temporal trends and identify high-exposure groups, as well as monitor implementation of the Stockholm Convention in Spain. This work was funded as part of a research agreement between the Spanish Ministry of Agriculture, Food and the Environment n° EG042007 and the Institute of Health Carlos III (project nos. SEG 1251/07 and 1210/10). The authors would like to thank S. González for the technical assistance, F. Cutanda for the helpful advice, and Silvia Gómez; the volunteers of BIOAMBIENT.ES and healthcare staff from the Societies for Prevention of IBERMUTUAMUR, MUTUALIA, MCPREVENCIÓN, MUGATRA, UNIMAT PREVENCIÓN, and PREVIMAC.