Serum Phthalate Concentrations and Biomarkers of Oxidative Stress in Adipose Tissue in a Spanish Adult Cohort.

The relationship between phthalates, a group of chemical pollutants classified as endocrine disruptors, and oxidative stress is not fully understood. The aim of the present hospital-based study was to explore the associations between circulating levels of 10 phthalate metabolites and 8 biomarkers of oxidative stress in adipose tissue. The study population (n = 143) was recruited in two hospitals in the province of Granada (Spain). Phthalate metabolite concentrations were analyzed by isotope diluted online-TurboFlow-LC-MS/MS in serum samples, while oxidative stress markers were measured by commercially available kits in adipose tissue collected during routine surgery. Statistical analyses were performed by MM estimators' robust linear regression and weighted quantile sum regression. Mainly, positive associations were observed of monomethyl phthalate (MMP), monoiso-butyl phthalate (MiBP), and mono-n-butyl phthalate (MnBP) (all low molecular weight phthalates) with glutathione peroxidase (GPx) and thiobarbituric acid reactive substances (TBARS), while an inverse association was found between monoiso-nonyl phthalate (MiNP) (high molecular weight phthalate) and the same biomarkers. WQS analyses showed significant effects of the phthalate mixture on GSH (ß = -30.089; p-value = 0.025) and GSSG levels (ß = -19.591; p-value = 0.030). Despite the limitations inherent to the cross-sectional design, our novel study underlines the potential influence of phthalate exposure on redox homeostasis, which warrants confirmation in further research.

From old pollutants to the regulation of bisphenol A: Lessons learned for health promotion and disease prevention.

Citizens deserve regulatory changes and policies more sensitive to the current needs of humans, the climate, and nature. In this work we draw on prior experiences of preventable human suffering and economic losses caused by delayed regulation of legacy and emerging pollutants. Heightened awareness of environmental health problems is necessary among health professionals, the media, and citizens' organizations. Improved translation from research to the clinical world and to policy is critical to reduce the population burden of diseases caused by exposure to endocrine disruptors and other environmental chemicals. Numerous lessons can be learned from science-to-policy processes built for "old pollutants" (as persistent organic pollutants, heavy metals, tributyltin), as well as from current trends regarding the regulation of non-persistent chemicals, such as the prototypical endocrine disruptor bisphenol A. We end discussing relevant pieces of the puzzle to tackle the environmental and regulatory challenges faced by our societies.

Associations of circulating levels of phthalate metabolites with cytokines and acute phase reactants in a Spanish human cohort.

The associations between human phthalate exposure and the onset of chronic diseases with an immunological component (e.g., metabolic syndrome, cancer) remain unclear, partly due to the uncertainties in the underlying mechanisms. This study investigates cross-sectional associations of the concentrations of 10 phthalate metabolites with 19 cytokines and acute phase proteins in 213 serum samples of Spanish adults. The associations were explored by Spearman's correlation, multivariable linear regression, and weighted quantile sum regression analyses. In the multivariable analyses, levels of plasminogen activator inhibitor (PAI)-1 were positively associated with mono-n-butyl phthalate (fold-change per one IQR increase in phthalate levels, 95% Confidence Interval: 1.65, 1.45-1.88) and mono-iso-butyl phthalate (3.07, 2.39-3.95), mono-ethyl phthalate (2.05, 1.62-2.61), as well as categorized mono-iso-decyl and mono-benzyl phthalates. The same phthalates also were significantly associated with leptin, interleukin (IL)-18 and monocyte chemoattractant protein-1. Moreover, the proinflammatory markers IL-1ß, IL-17, IL-8, IL-6, IL-12, tumor necrosis factor, and lipopolysaccharide-binding protein showed positive and negative associations with, respectively, mono-(2-ethyl-hexyl) and mono-methyl phthalates. Finally, phthalate mixtures were positively associated with PAI-1, leptin, IL-18, IL-12, IL-8 and IL-1ß. Despite the cross-sectional design limitation, these associations point to relevant subclinical immuno-inflammatory actions of these pollutants, warranting confirmation in future studies.

Human health risks associated with urban soils in mining areas.

We studied the chemical composition of As and Pb in total (<2 mm) and fine fractions (<50 µm) of 52 urban soil samples from Minas de Riotinto (mining area) and Aracena (non-exposed area) in SW Spain. In addition to a soil phytotoxicity bioassay using Lactuca Sativa L., we modelled and performed carcinogenic and non-carcinogenic human health risk assessment, later comparing our data with relative cancer mortality rates reported at the municipal level. This study demonstrates that mineralized bedrock and natural soil-forming processes affect the geochemistry of natural (in-situ) urban soils, which in many cases surpass the regulatory levels for As (36 mg/kg) and Pb (275 mg/kg). Fine fractions of in-situ and mixed urban soils -susceptible of inhalation- are significantly enriched in As and Pb with respect to fine fractions of aggregate materials (ex-situ soils of chalky sands and gravel) in Minas de Riotinto. The soils in Minas de Riotinto are significantly enriched in As (total and fine fractions) and Pb (total fraction) with respect to Aracena. Despite elevated bulk concentrations of As and Pb, only one in-situ sample exhibits phytotoxic effects of the soil-water extracts on Lactuca Sativa L. seeds. Health risk assessment of these towns as exposure areas indicates that the soils of Minas de Riotinto are indeed a health risk to the residents, whereas there is no potential risk in Aracena. The reported relative mortality rates in Minas de Riotinto show a greater mortality of carcinogenic tumors potentially related to As and Pb exposure, including lung cancer. Both soil type and use must be considered when administrators or policy-makers evaluate health risks involved in urbanistic decision-making. To minimize exposure risk and adverse health outcomes, we recommend that in-situ soils surpassing regulatory levels for As and Pb in public playgrounds and passing areas should be covered with aggregate materials.

Selecting the best non-invasive matrix to measure mercury exposure in human biomonitoring surveys.

Exposure to mercury, even at low doses, can affect human health, well-being and life quality at a broad scale. Human biomonitoring is the most straightforward approach to measure and quantify mercury exposure in humans. The objective of the present study is to compare and discuss the relationships between Hg levels in the most used matrices, hair, urine and blood, with the aim to ascertain to what extent mercury exposure and internal mercury levels could be predicted by monitoring non-invasive matrices. The study population (n = 527) is a subsample from Spanish BIOAMBIENT. ES study (18-65 y, both sexes), with data of Hg levels in blood, hair, and urine from the same individuals. We found strong inter-matrix Spearman correlations between blood and hair mercury (r2 = 0.84), while the correlations for urine and blood mercury (r2=0.64) and urine and hair mercury (r2=0.65) were weaker. The geometric mean of the ratios between matrices were (GM, 95%CI): Hair/Blood 280 (271-290), Urine/Blood 0.174 (0.163-0.186) and Hair/Urine 2070 (1953-2194) and Urine/Blood 0.135 (0.128-0.144) for urine corrected by creatinine. High individual variation was observed particularly in those ratios involving urine. Considering the wide range of values observed in the ratios, we do not recommend applying them at individual level. The predictive models indicate that hair Hg was a more accurate predictor than urine. The inclusion of urine values did not increase the predictive accuracy, so, we recommend a cautious interpretation of urine mercury levels. Our study presents clear evidence that in a population highly exposed to food-borne mercury, a large portion of urinary mercury primarily emanates from methylmercury demethylation. We conclude that urine, as a non-invasive matrix, can be used as a reliable qualitative biomarker for Hg exposure when hair measurements not are available. For quantitative individual assessments, still blood measurements are to be preferred.

Public healthcare costs associated with long-term exposure to mixtures of persistent organic pollutants in two areas of Southern Spain: A longitudinal analysis.

BACKGROUND: Polychlorinated biphenyls and organochlorine pesticides are persistent organic pollutants (POPs) that had been banned or restricted in many countries, including Spain. However, their ubiquity still poses environmental and human health threats. OBJECTIVE: To longitudinally explore public healthcare costs associated with long-term exposure to a mixture of 8 POPs in a cohort of residents of two areas of Granada Province, Southern Spain. METHODS: Longitudinal study in a subsample (n = 385) of GraMo adult cohort. Exposure assessment was performed by analyzing adipose tissue POP concentrations at recruitment. Average primary care (APC) and average hospital care (AHC) expenditures of each participant over 14 years were estimated using the data from their medical records. Data analyses were performed by robust MM regression, weighted quantile sum regression (WQS) and G-computation analysis. RESULTS: In the adjusted robust MM models for APC, most POPs showed positive beta coefficients, being Hexachlorobenzene (HCB) significantly associated (ß: 1.87; 95% Confidence interval (95%CI): 0.17, 3.57). The magnitude of this association increased (ß: 3.72; 95%CI: 0.80, 6.64) when the analyses were restricted to semi-rural residents, where ß-HCH was also marginally-significantly associated to APC (ß: 3.40; 95%CI: -0.10, 6.90). WQS revealed a positive but non-significant mixture association with APC (ß: 0.14; 95%CI: -0.06, 0.34), mainly accounted for by ß-HCH (54%) and HCB (43%), that was borderline-significant in the semi-rural residents (ß: 0.23; 95%CI: -0.01, 0.48). No significant results were observed in G-Computation analyses. CONCLUSION: Long-term exposure to POP mixtures might represent a modifiable factor increasing healthcare costs, thus affecting the efficiency of the healthcare systems. However, and owing the complexity of the potential causal pathways and the limitations of the present study, further research is warranted to fully elucidate ascertain whether interventions to reduce human exposure should be considered in healthcare policies.

Factors associated with the development of second primary tumours in head and neck cancer patients.

INTRODUCTION: The development of second primary tumours (SPTs) is one of the main causes of low survival in patients with head and neck cancer (HNC). The aim of this study was to review the evidence about factors associated with developing SPTs in patients with HNC. METHODS: An updated systematic review was performed according to the Preferred Reporting Items for Systematic Reviews and Meta-Analysis guidelines, and the search was performed in Pubmed and Scopus. Only original articles with a cohort or case-control design were included. Article quality was assessed with the Newcastle-Ottawa scale. RESULTS: Thirty-six and two case-control studies were included, with quality medium (n = 5) to high (n = 33). Tobacco showed a significant association with SPT development, with risks ranging from 1.41 (95%CI: 1.04-1.91) to 5.52 (95%CI: 2.91-10.49). Regarding alcohol, risks ranged from 1.46 (95%CI: 1.12-1.91) to 21.3 (95%CI: 2.9-156). Location of the index tumour in the hypopharynx/oropharynx, absence of human papillomavirus and presence of a premalignant lesion also increased the risk of SPTs. More controversy was found for sex, age and other clinical factors of the tumour. CONCLUSION: Toxic lifestyle habits and clinical factors were associated with the risk of SPTs in HNC patients. These findings may improve individualised prevention strategies in its follow-up.

Socio-Demographic Health Determinants Are Associated with Poor Prognosis in Spanish Patients Hospitalized with COVID-19.

INTRODUCTION: Social vulnerability is a known determinant of health in respiratory diseases. Our aim was to identify whether there are socio-demographic factors among COVID-19 patients hospitalized in Spain and their potential impact on health outcomes during the hospitalization. METHODS: A multicentric retrospective case series study based on administrative databases that included all COVID-19 cases admitted in 19 Spanish hospitals from 1 March to 15 April 2020. Socio-demographic data were collected. Outcomes were critical care admission and in-hospital mortality. RESULTS: We included 10,110 COVID-19 patients admitted to 18 Spanish hospitals (median age 68 (IQR 54-80) years old; 44.5% female; 14.8% were not born in Spain). Among these, 779 (7.7%) cases were admitted to critical care units and 1678 (16.6%) patients died during the hospitalization. Age, male gender, being immigrant, and low hospital saturation were independently associated with being admitted to an intensive care unit. Age, male gender, being immigrant, percentile of average per capita income, and hospital experience were independently associated with in-hospital mortality. CONCLUSIONS: Social determinants such as residence in low-income areas and being born in Latin American countries were associated with increased odds of being admitted to an intensive care unit and of in-hospital mortality. There was considerable variation in outcomes between different Spanish centers.

Associations of residential and occupational history with the distribution of persistent pollutant mixtures in adipose tissue samples.

This research aims to explore clusters of a mixture of 15 Persistent Toxic Substances (PTSs) in the adipose tissue of 227 individuals of an adult cohort from Granada Province (Southern Spain). Information about residence and occupation during participants lifetime was gathered by means of validated questionnaires. Clusters of pollutants in the study population were identified by Principal Component Analyses (PCA). PCA analyses revealed three major clusters of pollutants: PC1, representing predominantly an assortment of metal(loid)s, namely aluminium, arsenic, chromium, nickel and lead; PC2, including mostly Organochlorine Pesticides (OCPs), such as HCB, ß-HCH and p,p'-DDE; and PC3, gathering mainly a mixture of Polychlorinated Biphenyls (PCB-138, PCB-153 and PCB-180) and metals (cadmium, cobalt and chromium). The patterns of distribution of individual pollutants and their mixtures were explored through Geographic Information Systems and multivariable linear regression models. Living in rural areas was associated with decreased levels of the mixture of PCBs and metals. Residents of industrial and heavy traffic areas showed increased levels of the mixture of metal(loid)s. Those living in rural and semi-rural areas at recruitment had decreased levels of the OCP mixture. Occupational history related to agriculture and food industry was associated with increased levels of the mixture of metal(loid)s, whereas those who had been involved in motor and industrial activities showed increased levels of the OCP mixture. Participants who had worked in cleaning and housekeeping activities for long periods showed decreased levels of the mixture of PCBs and metals. Our research revealed suggestive clusters of exposure, that emphasized the need for further epidemiological studies to address the effect of environmental pollutants from a mixture perspective. Results also highlight the potential of adipose tissue as a matrix for exposure assessment to combinations of different families of contaminants.

Bisphenol-A exposure and risk of breast and prostate cancer in the Spanish European Prospective Investigation into Cancer and Nutrition study.

BACKGROUND: Bisphenol A (BPA) is an endocrine disruptor that it is present in numerous products of daily use. The aim of this study was to assess the potential association of serum BPA concentrations and the risk of incident breast and prostate cancer in a sub-cohort of the Spanish European Prospective Investigation into Cancer and Nutrition (EPIC). METHODS: We designed a case-cohort study within the EPIC-Spain cohort. Study population consisted on 4812 participants from 4 EPIC-Spain centers (547 breast cancer cases, 575 prostate cancer cases and 3690 sub-cohort participants). BPA exposure was assessed by means of chemical analyses of serum samples collected at recruitment. Borgan II weighted Cox regression was used to estimate hazard ratios. RESULTS: Median follow-up time in our study was 16.9 years. BPA geometric mean serum values of cases and sub-cohort were 1.12 ng/ml vs 1.10 ng/ml respectively for breast cancer and 1.33 ng/ml vs 1.29 ng/ml respectively for prostate cancer. When categorizing BPA into tertiles, a 40% increase in risk of prostate cancer for tertile 1 (p = 0.022), 37% increase for tertile 2 (p = 0.034) and 31% increase for tertile 3 (p = 0.072) was observed with respect to values bellow the limit of detection. No significant association was observed between BPA levels and breast cancer risk. CONCLUSIONS: We found a similar percentage of detection of BPA among cases and sub-cohort from our population, and no association with breast cancer risk was observed. However, we found a higher risk of prostate cancer for the increase in serum BPA levels. Further investigation is needed to understand the influence of BPA in prostate cancer risk.

Matrix metalloproteases and TIMPs as prognostic biomarkers in breast cancer patients treated with radiotherapy: A pilot study.

Breast cancer (BC) is the most common tumour in women and one of the most important causes of cancer death worldwide. Radiation therapy (RT) is widely used for BC treatment. Some proteins have been identified as prognostic factors for BC (Ki67, p53, E-cadherin, HER2). In the last years, it has been shown that variations in the expression of MMPs and TIMPs may contribute to the development of BC. The aim of this pilot work was to study the effects of RT on different MMPs (-1, -2, -3, -7, -8, -9, -10, -12 and -13) and TIMPs (-1 to -4), as well as their relationship with other variables related to patient characteristics and tumour biology. A group of 20 BC patients treated with RT were recruited. MMP and TIMP serum levels were analysed by immunoassay before, during and after RT. Our pilot study showed a slight increase in the levels of most MMP and TIMP with RT. However, RT produced a significantly decrease in TIMP-1 and TIMP-3 levels. Significant correlations were found between MMP-3 and TIMP-4 levels, and some of the variables studied related to patient characteristics and tumour biology. Moreover, MMP-9 and TIMP-3 levels could be predictive of RT toxicity. For this reason, MMP-3, MMP-9, TIMP-3 and TIMP-4 could be used as potential prognostic and predictive biomarkers for BC patients treated with RT.

Bisphenol-A in the European Prospective Investigation into Cancer and Nutrition cohort in Spain: Levels at recruitment and associated dietary factors.

Bisphenol A (BPA) is considered an endocrine disruptor and it is present in numerous products of daily use. The aim of this study was to analyze serum BPA concentrations in a subcohort of the Spanish European Prospective Investigation into Cancer and Nutrition (EPIC), as well as to identify potential predictors of the exposure. The population consisted on 3553 subjects from 4 EPIC-Spain centres and BPA levels were measured in serum samples by UHPLC-MS/MS. Almost 70% of the participants showed detectable BPA values (>0.2 ng/ml), with a geometric mean of 1.19 ng/ml (95% CI: 1.12-1.25). By sex, detectable percentages were similar (p = 0.56) but with higher serum levels in men (1.27 vs 1.11 ng/ml, p = 0.01). Based on the adjusted regression models, a 50 g/day increase in the consumption of added fats and oils were associated with 43% lower BPA serum levels, while sugar and confectionary was associated with 25% higher levels of serum BPA. We evidenced differential exposure levels by province, sex and age, but not by anthropometric or lifestyle characteristics. Further investigation is needed to understand the influence of diet in BPA exposure.

The efficacy of three-dimensional conformal radiation therapy on pain and quality of life in patients with painful bone metastases: a prospective study.

AIM: To evaluate the efficacy of radiation therapy in alleviating pain and improving the quality of life (QoL) with validated questionnaires in patients with painful bone metastases (BoM). METHODS: This prospective, observational study recruited 167 patients with painful BoM who were treated with palliative radiotherapy (PRT) from February 2015 to February 2018. After the first clinical assessment, the patients filled out specific questionnaires and underwent a fast radiotherapy treatment within 48 hours. The patients were followed up for eight weeks. RESULTS: The median age was 66.30 years. The most common primary cancer was lung cancer (31.1%). The most often prescribed scheme was 8 Gy in one fraction (70%). The patients experienced significant pain response and improved QoL compared with baseline, especially in the first two weeks after radiation. Overall, reduced pain and drug score were reported at two weeks of PRT in 68 (51.5%) and 37 (28%) of patients, respectively. CONCLUSIONS: PRT is an effective treatment option for patients with painful BoM.

Adverse effects of hexaclorobenzene exposure in children and adolescents.

BACKGROUND: Hexachlorobenzene (HCB: C6Cl6) is a persistent, bioaccumulative chemical formerly used worldwide in pesticide mixtures but also produced as a by-product in the chemical and metallurgical industry. Despite current international restrictions in the use and production of HCB, the majority of the general population still show detectable levels of HCB, which raises concerns on the potential health implications of the exposure. OBJECTIVE: To compile and synthesize the available scientific evidence regarding the adverse effects of exposure to HCB in children and adolescents. METHODS: A review of the literature focused on the adverse effects of HCB exposure in children. Eligible studies were systematically screened from searches in Medline, Scopus and Ebsco-host databases. A total of 62 studies were finally included. RESULTS AND DISCUSSION: In our search we found evidences of potential health effects linked to HCB exposure at different levels (e.g. neurotoxic, nephrotoxic, immunotoxic, hepatotoxic and toxicogenomic), although the conclusions are still contradictory. Further prospective research is needed, considering the special vulnerability of children and adolescent population as well as the ubiquity of the exposure.

Trust and distrust in relation to food risks in Spain: An approach to the socio-cultural representations of pregnant and breastfeeding women through the technique of free listing.

In this paper, we explore the socio-cultural representations of trust and distrust in relation to food risks among pregnant and breastfeeding women. We have conducted a study based on an analysis of cultural domains in order to understand how mothers incorporate different social meanings and explore the most important categories they use when talking about trust/distrust in relation to food. We use the technique of free listings to analyse the main shared items or elements regarding trust and distrust in food among these mothers. Through an analysis of cultural domains that refers to concepts and themes related to trust and distrust of foods that are important to these women, and through the study of shared knowledge about these domains, we examine their socio-cultural representations related to health and diet of the 65 free listings on trust and the 64 on distrust collected from mothers. The pregnant and breastfeeding women who participated in the free listings cite foods they trust or distrust based on the specific properties they perceive them to have or other characteristics related to their origin, their handling, processing and distribution. Additionally, trust/distrust often depends on the qualities they attribute to the product. This paper shows aspects of the socio-cultural representations of food risks in periods in the life cycle of women -pregnancy and breastfeeding-characterized by a risk discourse where the precautionary principle is frequently used to manage uncertainty. These results might help the development of public health campaigns as well as adapting the messages of the health authorities to the general population.

Industrial contaminated sites and health: results of a European survey.

BACKGROUND: industrially contaminated sites (ICSs) have been recognised as a major public health concern since they involve exposure to multiple environmental stressors, normally distributed unevenly within population. The COST Action on Industrially Contaminated Sites and Health Network (ICSHNet) comprises a European network of experts and institutions to clarify needs and priorities for better characterising the impact on environment and health of ICS. OBJECTIVES: evaluate the availability of information and studies concerning selected ICSs in participating Countries within the ICSHNet, with particular consideration on the accessibility to environmental, health and demographic data, and research and assessment tools. METHODS: to evaluate the availability of data, an Action Questionnaire (AQ) was developed based on previous questionnaires used in different European projects and on expert consultation. The AQ, with 84 items organised in eight sections, was adapted to an on-line version using the software LimeSurvey. The survey was sent to 47 participants within the ICSHNet, to report over a list of 99 ICSs previously identified. RESULTS: information was gathered from 81 sites out of the initially selected 99, reported by 45 participants from 27 Countries (82% of Countries in the ICSHNet). The predominant polluting activities were waste disposal (46%) and chemical industries (37%), affecting all environmental media, but more extensively surface and groundwater (70%) and soil (68%). Main categories of contaminants affecting different media were heavy metals and chlorinated hydrocarbons, but also BTEX (benzene, toluene, ethylbenzene, and xylene) and ambient air pollutants (e.g., particulate matter, SOx). Human health risk assessment was the most prevalent methodological approach for characterising impacts on health (32%), followed by epidemiological studies (26%), and health impact assessment (12%). The low reporting, both referring to data availability or methodologies, could be due to absence of data, or to the fact that the reporting person (many of them from the public health sector) did not know how to reach the environmental information. CONCLUSIONS: survey findings suggest that improving the collection and access to specific environmental, health and demographic data related to ICSs is crucial to meet the methodological requirement to better analyse the health impact of ICSs.

Human biomonitoring as a tool for exposure assessment in industrially contaminated sites (ICSs). Lessons learned within the ICS and Health European Network.

BACKGROUND: the mixed and complex nature of industrially contaminated sites (ICSs) leads to heterogeneity in exposure and health risk of residents living nearby. Health, environment, and social aspects are strongly interconnected in ICSs, and local communities are often concerned about potential health impact and needs for remediation. The use of human biomonitoring (HBM) for impact assessment of environmental exposure is increasing in Europe. The COST Action IS1408 on Industrially Contaminated Sites and Health Network (ICSHNet) decided to reflect on the potential and limitations of HBM to assess exposure and early health effects associated with living near ICSs. OBJECTIVES: to discuss challenges and lessons learned for addressing environmental health impact near ICSs with HBM in order to identify needs and priorities for HBM guidelines in European ICSs. METHODS: based on the experience of the ICSHNet research team, six case studies from different European regions that applied HBM at ICSs were selected. The case studies were systematically compared distinguishing four phases: the preparatory phase; study design; study results; the impact of the results at scientific, societal, and political levels. RESULTS: all six case studies identified opportunities and challenges for applying HBM in ICS studies. A smart choice of (a combination of) sample matrices for biomarker analysis produced information about relevant time-windows of exposure which matched with the activities of the ICSs. Combining biomarkers of exposure with biomarkers of (early) biological effects, data from questionnaires or environmental data enabled fine-tuning of the results and allowed for more targeted remediating actions aimed to reduce exposure. Open and transparent communication of study results with contextual information and involvement of local stakeholders throughout the study helped to build confidence in the study results, gained support for remediating actions, and facilitated sharing of responsibilities. Using HBM in these ICS studies helped in setting priorities in policy actions and in further research. Limitations were the size of the study population, difficulties in recruiting vulnerable target populations, availability of validated biomarkers, and coping with exposure to mixtures of chemicals. CONCLUSIONS: based on the identified positive experiences and challenges, the paper concludes with formulating recommendations for a European protocol and guidance document for HBM in ICS. This could advance the use of HBM in local environmental health policy development and evaluation of exposure levels, and promote coordination and collaboration between researchers and risk managers.

Relationship between exposure to parabens and benzophenones and prostate cancer risk in the EPIC-Spain cohort.

The etiology of prostate cancer is not fully elucidated. Among environmental risk factors, endocrine-disrupting chemicals (EDCs) deserve special mention, as they alter metabolic pathways involved in hormone-dependent cancers. Epidemiological evidence assessing the carcinogenicity of EDCs is scarce. The aim of this study was to analyze the relationship between exposure to parabens and benzophenones and prostate cancer risk. We conducted a case-cohort study nested within the EPIC-Spain prospective multi-center cohort. Study population comprised 1,838 sub-cohort participants and 467 non-sub-cohort prostate cancer cases. Serum concentrations of four parabens and two benzophenones were assessed at recruitment. Covariates included age, physical activity, tobacco smoking, alcohol consumption, body mass index, educational level and diabetes. Borgan II weighted Cox proportional hazard models stratified by study center were applied. Median follow-up time was 18.6 years (range = 1.0-21.7 years). Most sub-cohort participants reached primary education at most (65.5%), were overweight (57.7%) and had a low level of physical activity (51.3%). Detection percentages varied widely, being lowest for butyl-paraben (11.3%) and highest for methyl-paraben (80.7%), which also showed the highest geometric mean (0.95 ng/ml). Cases showed significantly higher concentrations of methyl-paraben (p = 0.041) and propyl-paraben (p < 0.001). In the multivariable analysis, methyl-paraben - log-transformed (HR = 1.07; 95%CI = 1.01-1.12) and categorized into tertiles (HR = 1.60 for T3; 95%CI = 1.16-2.20) -, butyl-paraben - linear (HR = 1.19; 95%CI = 1.14-1.23) and log-transformed (HR = 1.17; 95%CI = 1.01-1.35) - and total parabens - log-transformed (HR = 1.09; 95%CI = 1.02-1.17) and categorized into tertiles (HR = 1.62 for T3; 95%CI = 1.10-2.40) - were associated with an increased prostate cancer risk. In this study, higher concentrations of methyl-, butyl-, and total parabens were positively associated with prostate cancer risk. Further research is warranted to confirm these findings.

Demographic and Socioeconomic Factors Associated to Fruits and Vegetables Consumption in Elderly Europeans: A Systematic Review.

Several epidemiological studies stress the association between a diet based on high fruits and vegetables intake and a better health condition. However, elderly Europeans cannot manage the recommended fruits and vegetables consumption. This systematic review aims to explore the main factors related to fruits and vegetables consumption in elderly Europeans. We conducted literature searches on Medline, Scopus, and Web of Science from inception to May 2022. Published articles including data related to certain fruits and vegetables consumption among elderly Europeans were selected. The New Castle-Ottawa Scale and National Heart, Lung, and Blood Institute tools were used for methodological quality assessment by two authors independently. A total of 60 articles were retrieved, and data from twenty-one high-quality cross-sectional studies and five moderate-to-high-quality cohort studies, including a total of 109,516 participants, were synthesized. Associated factors mostly analyzed were those relating to demographic and socioeconomic status, such as sex, age, marital status, educational level, and income. However, the findings show a high discrepancy. Some evidence suggests a possible positive association, while other evidence shows an inverse or no association at all. The relationship between demographic and socioeconomic factors with fruits and vegetables consumption is not at all clear. More epidemiological studies with an appropriate design and corresponding statistical methods are required.

Blood Levels of Organochlorine Contaminants Mixtures and Cardiovascular Disease.

Importance: Cardiovascular toxic effects derived from high exposures to individual organochlorine compounds are well documented. However, there is no evidence on low but continuous exposure to combined organochlorine compounds in the general population. Objective: To evaluate the association of combined exposure to several organochlorine compounds, including organochlorine pesticides and polychlorinated biphenyls, with incident cardiovascular disease (CVD) in the general population. Design, Setting, and Participants: This prospective nested case-control study included data from 2 cohorts: the Swedish Mammography Cohort-Clinical (SMC-C) and the Cohort of 60-Year-Olds (60YO), with matched case-control pairs based on age, sex, and sample date. Baseline blood sampling occurred from November 2003 to September 2009 (SMC-C) and from August 1997 to March 1999 (60YO), with follow-up through December 2017 (SMC-C) and December 2014 (60YO). Participants with myocardial infarction or ischemic stroke were matched with controls for composite CVD evaluation. Data were analyzed from September 2020 to May 2023. Exposures: A total of 25 organochlorine compounds were measured in blood at baseline by gas chromatography-triple quadrupole mass spectrometry. For 7 compounds, more than 75% of the samples were lower than the limit of detection and not included. Main Outcomes and Measures: Incident cases of primary myocardial infarction and ischemic stroke were ascertained via linkage to the National Patient Register (International Statistical Classification of Diseases and Related Health Problems, Tenth Revision codes I21 and I63). The quantile-based g-computation method was used to estimate the association between the combined exposure to several organochlorine compounds and composite CVD. Results: Of 1528 included participants, 1024 (67.0%) were female, and the mean (SD) age was 72 (7.0) years in the SMC-C and 61 (0.1) years in the 60YO. The odds ratio of composite CVD was 1.71 (95% CI, 1.11-2.64) per 1-quartile increment of total organochlorine compounds mixture. Organochlorinated pesticides were the largest contributors, and ß-hexachlorocyclohexane and transnonachlor had the highest impact. Most of the outcome was not explained by disturbances in the main cardiometabolic risk factors, ie, high body mass index, hypertension, lipid alteration, or diabetes. Conclusions and Relevance: In this prospective nested case-control study, participants with higher exposures to organochlorines had an increased probability of experiencing a cardiovascular event, the major cause of death worldwide. Measures may be required to reduce these exposures.