Prepandemic personal concentrations of per- and polyfluoroalkyl substances (PFAS) and other pollutants: Specific and combined effects on the incidence of COVID-19 disease and SARS-CoV-2 infection.

OBJECTIVE: To investigate the specific and combined effects of personal concentrations of some per- and polyfluoroalkyl substances (PFAS), other persistent organic pollutants (POPs), and chemical elements -measured in individuals' blood several years before the pandemic- on the development of SARS-CoV-2 infection and COVID-19 disease in the general population. METHODS: We conducted a prospective cohort study in 240 individuals from the general population of Barcelona. PFAS, other POPs, and chemical elements were measured in plasma, serum, and whole blood samples, respectively, collected in 2016-2017. PFAS were analyzed by liquid chromatography-triple quadrupole mass spectrometry. SARS-CoV-2 infection was detected by rRT-PCR in nasopharyngeal swabs and/or antibody serology in blood samples collected in 2020-2021. RESULTS: No individual PFAS nor their mixtures were significantly associated with SARS-CoV-2 seropositivity or COVID-19 disease. Previously identified mixtures of POPs and elements (Porta et al., 2023) remained significantly associated with seropositivity and COVID-19 when adjusted for PFAS (all OR > 4 or p < 0.05). Nine chemicals comprised mixtures associated with COVID-19: thallium, ruthenium, lead, benzo[b]fluoranthene, DDD, other DDT-related compounds, manganese, tantalum, and aluminium. And nine chemicals comprised the mixtures more consistently associated with SARS-CoV-2 seropositivity: thallium, ruthenium, lead, benzo[b]fluoranthene, DDD, gold, and (protectively) selenium, indium, and iron. CONCLUSIONS: The PFAS studied were not associated with SARS-CoV-2 seropositivity or COVID-19. The results confirm the associations between personal blood concentrations of some POPs and chemical elements and the risk of COVID-19 and SARS-CoV-2 infection in what remains the only prospective and population-based cohort study on the topic. Mixtures of POPs and chemical elements may contribute to explain the heterogeneity in the risks of SARS-CoV-2 infection and COVID-19 in the general population.

Supporting legislative action: Urinary levels of phthalates and phenols among influencers in the 'Plastics in the spotlight' advocacy initiative.

BACKGROUND: Society-wide initiatives to prevent human exposure to plastic residues include laws and policies. Such measures require citizens' support, which can be increased by honest advocacy and pedagogic projects. These efforts must have a scientific basis. OBJECTIVE: To assist the 'Plastics in the spotlight' advocacy initiative raise awareness among the general public of the presence of plastic residues in the human body, and to increase citizens' support for legislation on plastic control in the European Union. METHODS: Spot urine samples of 69 volunteers with cultural and political influence from Spain, Portugal, Latvia, Slovenia, Belgium, and Bulgaria were collected. Concentrations of 30 phthalate metabolites and phenols were determined through a high-performance liquid chromatography with tandem mass spectrometry and ultra-high-performance liquid chromatography with tandem mass spectrometry, respectively. RESULTS: At least 18 compounds were detected in all urine samples. The maximum number of compounds detected per participant was 23, and the mean, 20.5. Phthalates were detected more frequently than phenols. Median concentrations were highest for monoethyl phthalate (41.6 ng/mL, adjusted for specific gravity), and maximum concentrations were highest for mono-iso-butyl phthalate (1345.1 ng/mL), oxybenzone (1915.1 ng/mL), and triclosan (949.6 ng/mL). Most reference values were not exceeded. Women had higher concentrations of the 14 phthalate metabolites and oxybenzone than men. Urinary concentrations were not correlated with age. DISCUSSION: The study had three main limitations: method of subject selection (volunteers), small sample size, and limited data on determinants of exposure. Studies on volunteers do not pretend to be representative of the general population and are no substitute for biomonitoring studies in representative samples of the populations of interest. Studies as ours can only illustrate the existence and some aspects of the problem, and can raise awareness among citizens concerned by the evidence that the studies provide in a group of subjects who are humanly appealing. CONCLUSIONS: The results illustrate that human exposure to phthalates and phenols is widespread. All countries appeared to be similarly exposed to these contaminants, with higher levels in females. Most concentrations did not exceed reference values. The effects of this study on the objectives of the 'Plastics in the spotlight' advocacy initiative deserve a specific analysis from policy science.

Individual blood concentrations of persistent organic pollutants and chemical elements, and COVID-19: A prospective cohort study in Barcelona.

BACKGROUND: There is wide, largely unexplained heterogeneity in immunological and clinical responses to SARS-CoV-2 infection. Numerous environmental chemicals, such as persistent organic pollutants (POPs) and chemical elements (including some metals, essential trace elements, rare earth elements, and minority elements), are immunomodulatory and cause a range of adverse clinical events. There are no prospective studies on the effects of such substances on the incidence of SARS-CoV-2 infection and COVID-19. OBJECTIVE: To investigate the influence of blood concentrations of POPs and elements measured several years before the pandemic on the development of SARS-CoV-2 infection and COVID-19 in individuals from the general population. METHODS: We conducted a prospective cohort study in 154 individuals from the general population of Barcelona. POPs and elements were measured in blood samples collected in 2016-2017. SARS-CoV-2 infection was detected by rRT-PCR in nasopharyngeal swabs and/or by antibody serology using eighteen isotype-antigen combinations measured in blood samples collected in 2020-2021. We analyzed the associations between concentrations of the contaminants and SARS-CoV-2 infection and development of COVID-19, taking into account personal habits and living conditions during the pandemic. RESULTS: Several historically prevalent POPs, as well as arsenic, cadmium, mercury, and zinc, were not associated with COVID-19, nor with SARS-CoV-2 infection. However, DDE (adjusted OR = 5.0 [95% CI: 1.2-21]), lead (3.9 [1.0-15]), thallium (3.4 [1.0-11]), and ruthenium (5.0 [1.8-14]) were associated with COVID-19, as were tantalum, benzo(b)fluoranthene, DDD, and manganese. Thallium (3.8 [1.6-8.9]), and ruthenium (2.9 [1.3-6.7]) were associated with SARS-CoV-2 infection, and so were lead, gold, and (protectively) iron and selenium. We identified mixtures of up to five substances from several chemical groups, with all substances independently associated to the outcomes. CONCLUSIONS: Our results provide the first prospective and population-based evidence of an association between individual concentrations of some contaminants and COVID-19 and SARS-CoV-2 infection. POPs and elements may contribute to explain the heterogeneity in the development of SARS-CoV-2 infection and COVID-19 in the general population. If the associations are confirmed as causal, means are available to mitigate the corresponding risks.

Timing of Toenail Collection and Concentrations of Metals in Pancreatic Cancer. Evidence Against Disease Progression Bias.

Trace elements such as cadmium, arsenic, zinc or selenium increase or decrease risk of a wide range of human diseases. Their levels in toenails may provide a measure of mid-term intake of trace elements for studies in humans. However, in biologically and clinically aggressive diseases as pancreatic cancer, the progression of the disease could modify such concentrations and produce reverse causation bias. The aim was to analyze the influence of specific time intervals between several clinical events and the collection of toenails upon concentrations of trace elements in patients with pancreatic cancer. Subjects were 118 incident cases of pancreatic adenocarcinoma prospectively recruited in eastern Spain. Toenails were collected at cancer diagnosis, and soon thereafter interviews were conducted. Information on cancer signs and symptoms was obtained from medical records and patient interviews. Levels of 12 trace elements were determined in toenail samples by inductively coupled plasma mass spectrometry. General linear models adjusting for potential confounders were applied to analyze relations between log concentrations of trace elements and the time intervals, including the interval from first symptom of cancer to toenail collection (iST). Toenail concentrations of the 12 trace elements were weakly or not influenced by the progression of the disease or the diagnostic procedures. Concentrations of aluminum were slightly higher in subjects with a longer iST (age, sex and stage adjusted geometric means: 11.44 vs. 7.75 µg/g for iST > 120 days vs. ≤ 40 days). There was a weak inverse relation of iST with concentrations of zinc and selenium (maximum differences of about 20 and 0.08 µg/g, respectively). Conclusions: concentrations of the trace elements were weakly or not influenced by the development of the disease before toenail collection. Only concentrations of aluminum increased slightly with increasing iST, whereas levels of zinc and selenium decreased weakly. Even in an aggressive disease as pancreatic cancer, toenail concentrations of trace elements may provide a valid measure of mid-term intake of trace elements, unaffected by clinical events and disease progression. Supplementary Information: The online version contains supplementary material available at 10.1007/s12403-021-00436-2.

Plasma concentrations of persistent organic pollutants and pancreatic cancer risk.

BACKGROUND: Findings and limitations of previous studies on persistent organic pollutants (POPs) and pancreatic cancer risk support conducting further research in prospective cohorts. METHODS: We conducted a prospective case-control study nested within the European Prospective Investigation into Cancer and Nutrition (EPIC) cohort. Participants were 513 pancreatic cancer cases and 1020 matched controls. Concentrations of 22 POPs were measured in plasma collected at baseline. RESULTS: Some associations were observed at higher concentrations of p, p'-DDT, trans-nonachlor, ß-hexachlorocyclohexane and the sum of six organochlorine pesticides and of 16 POPs. The odds ratio (OR) for the upper quartile of trans-nonachlor was 1.55 (95% confidence interval 1.06-2.26; P for trend = 0.025). Associations were stronger in the groups predefined as most valid (participants having fasted >6 h, with microscopic diagnostic confirmation, normal weight, and never smokers), and as most relevant (follow-up ≥10 years). Among participants having fasted >6 h, the ORs were relevant for 10 of 11 exposures. Higher ORs were also observed among cases with microscopic confirmation than in cases with a clinical diagnosis, and among normal-weight participants than in the rest of participants. Among participants with a follow-up ≥10 years, estimates were higher than in participants with a shorter follow-up (for trans-nonachlor: OR = 2.14, 1.01 to 4.53, P for trend = 0.035). Overall, trans-nonachlor, three PCBs and the two sums of POPs were the exposures most clearly associated with pancreatic cancer risk. CONCLUSIONS: Individually or in combination, most of the 22 POPs analysed did not or only moderately increased the risk of pancreatic cancer.

Influence of KRAS mutations, persistent organic pollutants, and trace elements on survival from pancreatic ductal adenocarcinoma.

INTRODUCTION: Reasons why pancreatic ductal adenocarcinoma (PDAC) continues to have poor survival are only partly known. No previous studies have analyzed the combined influence of KRAS mutations, persistent organic pollutants (POPs), and trace elements upon survival in PDAC or in any other human cancer. OBJECTIVE: To analyze the individual and combined influence of KRAS mutations, POPs, and trace elements upon survival from PDAC. METHODS: Incident cases of PDAC (n = 185) were prospectively identified in five hospitals in Eastern Spain in 1992-1995 and interviewed face-to-face during hospital admission. KRAS mutational status was determined from tumour tissue through polymerase chain reaction and artificial restriction fragment length polymorphism. Blood and toenail samples were obtained before treatment. Serum concentrations of POPs were analyzed by high-resolution gas chromatography with electron-capture detection. Concentrations of 12 trace elements were determined in toenail samples by inductively coupled plasma mass spectrometry. Multivariable Cox proportional hazards regression was used to assess prognostic associations. RESULTS: Patients with a KRAS mutated tumor had a 70% higher risk of early death than patients with a KRAS wild-type PDAC (hazard ratio [HR] = 1.7, p = 0.026), adjusting for age, sex, and tumor stage. KRAS mutational status was only modestly and not statistically significantly associated with survival when further adjusting by treatment or by treatment intention. The beneficial effects of treatment remained unaltered when KRAS mutational status was taken into account, and treatment did not appear to be less effective in the subgroup of patients with a KRAS mutated tumor. POPs did not materially influence survival: the adjusted HR of the highest POP tertiles was near unity for all POPs. When considering the joint effect on survival of POPs and KRAS, patients with KRAS mutated tumors had modest and nonsignificant HRs (most HRs around 1.3 to 1.4). Higher concentrations of lead, cadmium, arsenic, vanadium, and aluminium were associated with better survival. When KRAS status, POPs, and trace elements were simultaneously considered along with treatment, only the latter was statistically significantly related to survival. CONCLUSIONS: In this study based on molecular, clinical, and environmental epidemiology, KRAS mutational status, POPs, and trace elements were not adversely related to PDAC survival when treatment was simultaneously considered; only treatment was independently related to survival. The lack of adverse prognostic effects of POPs and metals measured at the time of diagnosis provide scientific and clinical reassurance on the effects of such exposures upon survival of patients with PDAC. The weak association with KRAS mutations contributes to the scant knowledge on the clinical implications of a genetic alteration highly frequent in PDAC.

Concentrations of trace elements and KRAS mutations in pancreatic ductal adenocarcinoma.

Trace elements are a possible risk factor for pancreatic ductal adenocarcinoma (PDAC). However, their role in the occurrence and persistence of KRAS mutations remains unstudied. There appear to be no studies analyzing biomarkers of trace elements and KRAS mutations in any human cancer. We aimed to determine whether patients with KRAS mutated and nonmutated tumors exhibit differences in concentrations of trace elements. Incident cases of PDAC were prospectively identified in five hospitals in Spain. KRAS mutational status was determined through polymerase chain reaction from tumor tissue. Concentrations of 12 trace elements were determined in toenail samples by inductively coupled plasma mass spectrometry. Concentrations of trace elements were compared in 78 PDAC cases and 416 hospital-based controls (case-control analyses), and between 17 KRAS wild-type tumors and 61 KRAS mutated tumors (case-case analyses). Higher levels of iron, arsenic, and vanadium were associated with a statistically nonsignificant increased risk of a KRAS wild-type PDAC (OR for higher tertile of arsenic = 3.37, 95% CI 0.98-11.57). Lower levels of nickel and manganese were associated with a statistically significant higher risk of a KRAS mutated PDAC (OR for manganese = 0.34, 95% CI 0.14-0.80). Higher levels of selenium appeared protective for both mutated and KRAS wild-type PDAC. Higher levels of cadmium and lead were clear risk factors for both KRAS mutated and wild-type cases. This is the first study analyzing biomarkers of trace elements and KRAS mutations in any human cancer. Concentrations of trace elements differed markedly between PDAC cases with and without mutations in codon 12 of the KRAS oncogene, thus suggesting a role for trace elements in pancreatic and perhaps other cancers with such mutations. Environ. Mol. Mutagen., 60:693-703, 2019. © 2019 Wiley Periodicals, Inc.

Toenail concentrations of trace elements and occupational history in pancreatic cancer.

BACKGROUND: Some occupations potentially entailing exposure to cadmium, arsenic, lead, selenium, nickel, and chromium have been associated with an increased risk of exocrine pancreatic cancer (EPC), but no studies have assessed whether body concentrations of such compounds differed among subjects occupationally exposed and unexposed. No studies which found that exposure to such metals increased the risk of EPC assessed whether past occupations were the source of exposure. OBJECTIVE: The aim was to analyse the relationship between toenail concentrations of trace elements and occupational history in EPC patients. METHODS: The study included 114 EPC cases personally interviewed on occupational history and lifestyle factors. Occupations were coded according to the International Standard Classification of Occupations 1988. Selected occupational exposures were assessed by two industrial hygienists and with the Finnish job-exposure matrix (Finjem). Concentrations of 12 trace elements were determined in toenail samples by inductively coupled plasma mass spectrometry. Adjusted geometric means (aGMs) and 95% confidence intervals (95% CI) were calculated. RESULTS: Patients occupationally exposed to aromatic hydrocarbon solvents (AHs) had higher concentrations of cadmium, manganese, lead, iron and vanadium. The aGM of cadmium concentrations for cases exposed to any pesticide was 0.056 µg/g [95% CI: 0.029-0.108], and, for unexposed cases, 0.023 µg/g [0.017-0.031]. Patients occupationally exposed to pesticides had higher concentrations of cadmium and manganese. Higher concentrations of vanadium, lead and arsenic were related to exposure to formaldehyde. Vanadium and lead were also associated with exposure to chlorinated hydrocarbon solvents, and arsenic was related to exposure to polycyclic aromatic hydrocarbons (PAHs). CONCLUSIONS: Patients occupationally exposed to AHs, pesticides, chlorinated hydrocarbon solvents, formaldehyde, volatile sulphur compounds and PAHs had higher concentrations of several metals. These elements may account for some of the occupational risks previously reported for pancreatic cancer.

Methodological issues in a prospective study on plasma concentrations of persistent organic pollutants and pancreatic cancer risk within the EPIC cohort.

BACKGROUND: The use of biomarkers of environmental exposure to explore new risk factors for pancreatic cancer presents clinical, logistic, and methodological challenges that are also relevant in research on other complex diseases. OBJECTIVES: First, to summarize the main design features of a prospective case-control study -nested within the European Prospective Investigation into Cancer and Nutrition (EPIC) cohort- on plasma concentrations of persistent organic pollutants (POPs) and pancreatic cancer risk. And second, to assess the main methodological challenges posed by associations among characteristics and habits of study participants, fasting status, time from blood draw to cancer diagnosis, disease progression bias, basis of cancer diagnosis, and plasma concentrations of lipids and POPs. Results from etiologic analyses on POPs and pancreatic cancer risk, and other analyses, will be reported in future articles. METHODS: Study subjects were 1533 participants (513 cases and 1020 controls matched by study centre, sex, age at blood collection, date and time of blood collection, and fasting status) enrolled between 1992 and 2000. Plasma concentrations of 22 POPs were measured by gas chromatography - triple quadrupole mass spectrometry (GC-MS/MS). To estimate the magnitude of the associations we calculated multivariate-adjusted odds ratios by unconditional logistic regression, and adjusted geometric means by General Linear Regression Models. RESULTS: There were differences among countries in subjects' characteristics (as age, gender, smoking, lipid and POP concentrations), and in study characteristics (as time from blood collection to index date, year of last follow-up, length of follow-up, basis of cancer diagnosis, and fasting status). Adjusting for centre and time of blood collection, no factors were significantly associated with fasting status. Plasma concentrations of lipids were related to age, body mass index, fasting, country, and smoking. We detected and quantified 16 of the 22 POPs in more than 90% of individuals. All 22 POPs were detected in some participants, and the smallest number of POPs detected in one person was 15 (median, 19) with few differences by country. The highest concentrations were found for p,p'-DDE, PCBs 153 and 180 (median concentration: 3371, 1023, and 810 pg/mL, respectively). We assessed the possible occurrence of disease progression bias (DPB) in eight situations defined by lipid and POP measurements, on one hand, and by four factors: interval from blood draw to index date, tumour subsite, tumour stage, and grade of differentiation, on the other. In seven of the eight situations results supported the absence of DPB. CONCLUSIONS: The coexistence of differences across study centres in some design features and participant characteristics is of relevance to other multicentre studies. Relationships among subjects' characteristics and among such characteristics and design features may play important roles in the forthcoming analyses on the association between plasma concentrations of POPs and pancreatic cancer risk.

Blood Concentrations of Persistent Organic Pollutants and Unhealthy Metabolic Phenotypes in Normal-Weight, Overweight, and Obese Individuals.

Factors underlying metabolic phenotypes, such as the metabolically healthy but obese phenotype, remain unclear. Differences in metabolic phenotypes-particularly, among individuals with a similar body mass index-could be related to concentrations of persistent organic pollutants (POPs). To our knowledge, no studies have analyzed POPs and metabolic phenotypes in normal-weight persons. We investigated the relationships between serum concentrations of POPs and metabolic phenotypes in 860 normal-weight, overweight, and obese participants in the 2002 Catalan Health Interview Survey (Spain). POP concentrations were significantly higher in metabolically unhealthy than in metabolically healthy individuals. In models adjusting for body mass index and other confounders, hexachlorobenzene, ß-hexachlorocyclohexane, and polychlorinated biphenyls were associated with the unhealthy metabolic phenotype and metabolic syndrome. Among normal-weight individuals, the adjusted prevalence ratio of having an unhealthy phenotype for the upper category of the sum of orders of the 6 mentioned POPs (all individually associated with metabolic phenotypes) was 4.1 (95% confidence interval: 1.7, 10.0). Among overweight and obese individuals, the corresponding prevalence ratio for the sum of polychlorinated biphenyls was 1.4 (95% confidence interval: 1.0, 1.8). Our results supported the hypothesis that POP concentrations are associated with unhealthy metabolic phenotypes, not only in obese and overweight individuals but also (and probably more strongly) in normal-weight individuals.

Citizens' perceptions of the presence and health risks of synthetic chemicals in food: results of an online survey in Spain / Percepciones de la ciudadanía sobre la presencia y los riesgos para la salud de compuestos químicos sintéticos en los alimentos: resultados de un estudio en línea en España

Objective: To explore factors influencing perceptions and viewpoints on the responsibility for the presence of toxic substances in food, on enforcement of laws and regulations that control human exposure to toxic substances in food, and on the effectiveness of such regulations. Methods: An online survey was completed by 740 individuals from several parts of Spain (median age, 47 years; 67% were women; 70% had completed university studies). Results: Over 87% of respondents said that it was possible that throughout their lives they could have accumulated in their body toxic substances potentially dangerous to their health. The attribution of the responsibility for toxic substances in food to a larger number of social groups was more frequent among respondents who consulted information about the problem more often (odds ratio [OR]: 1.92), who correctly identified factors that increase the likelihood of toxic substances in food being harmful to human health (OR: 2.86), who better knew the health problems that may be caused by such substances (OR: 2.48), and who recognised more food groups that tend to have concentrations of toxic substances potentially harmful to health (OR: 2.92) (all p values <0.001). Women were 65% less likely than men to answer that regulations on toxic substances in food are effective (p<0.001); and so were participants who identified more food groups with potentially toxic concentrations. Conclusions: Among study participants there was a widespread scepticism and distrust towards the enforcement and effectiveness of laws and regulations that in Spain aim to control human exposure to toxic substances in food (AU)

Objetivo: Explorar factores que influyen en las percepciones y puntos de vista de los ciudadanos sobre la responsabilidad de la presencia de sustancias tóxicas en los alimentos, sobre la aplicación de las leyes que en España controlan la exposición humana a dichas sustancias y sobre la efectividad de tales leyes. Método: 740 personas de varias partes de España (mediana de edad, 47 años; 67% mujeres; 70% con estudios universitarios) completaron una encuesta en línea. Resultados: Más del 87% de las personas encuestadas consideraron que era posible que a lo largo de su vida hubiesen acumulado en su cuerpo sustancias tóxicas potencialmente peligrosas para su salud. Atribuir la responsabilidad sobre la presencia de sustancias tóxicas en los alimentos a un mayor número de grupos sociales fue más frecuente entre quienes declararon consultar con más frecuencia información sobre el problema (odds ratio [OR]: 1,92), quienes identificaron correctamente factores que aumentan la probabilidad de que las sustancias tóxicas en los alimentos sean perjudiciales para la salud humana (OR: 2,86), quienes conocían mejor los problemas de salud que pueden ser causados por dichas sustancias (OR: 2,48) y quienes señalaron más grupos de alimentos que tienden a tener concentraciones de tóxicos que pueden ser perjudiciales para la salud (OR: 2,92) (todos los valores de p <0,001). Las mujeres fueron un 65% menos propensas que los hombres a responder que las regulaciones legales sobre sustancias tóxicas en los alimentos son efectivas (p <0,001), y también lo fueron las personas que identificaron más grupos de alimentos con concentraciones potencialmente tóxicas. Conclusiones: Entre los/las participantes en el estudio hubo un amplio escepticismo y desconfianza respecto a la aplicación y la efectividad de la legislación que en España aspira a controlar la exposición humana a sustancias tóxicas en los alimentos (AU)

Citizens' perceptions of the presence and health risks of synthetic chemicals in food: results of an online survey in Spain.

OBJECTIVE: To explore factors influencing perceptions and viewpoints on the responsibility for the presence of toxic substances in food, on enforcement of laws and regulations that control human exposure to toxic substances in food, and on the effectiveness of such regulations. METHODS: An online survey was completed by 740 individuals from several parts of Spain (median age, 47 years; 67% were women; 70% had completed university studies). RESULTS: Over 87% of respondents said that it was possible that throughout their lives they could have accumulated in their body toxic substances potentially dangerous to their health. The attribution of the responsibility for toxic substances in food to a larger number of social groups was more frequent among respondents who consulted information about the problem more often (odds ratio [OR]: 1.92), who correctly identified factors that increase the likelihood of toxic substances in food being harmful to human health (OR: 2.86), who better knew the health problems that may be caused by such substances (OR: 2.48), and who recognised more food groups that tend to have concentrations of toxic substances potentially harmful to health (OR: 2.92) (all p values <0.001). Women were 65% less likely than men to answer that regulations on toxic substances in food are effective (p<0.001); and so were participants who identified more food groups with potentially toxic concentrations. CONCLUSIONS: Among study participants there was a widespread scepticism and distrust towards the enforcement and effectiveness of laws and regulations that in Spain aim to control human exposure to toxic substances in food.

Number of Persistent Organic Pollutants Detected at High Concentrations in Blood Samples of the United States Population.

Human exposure to environmental chemicals as persistent organic pollutants (POPs) is usually assessed considering each pollutant individually, with little attention to concentrations of mixtures in individuals or social groups. Yet, it may be relatively common for humans to have low and high concentrations of numerous POPs. The study objectives were to analyze the number of POPs detected per person at high concentrations in the U.S. population, and the associations between such type of indicators and socioeconomic factors as gender, race / ethnicity, education, and poverty level. From 91 POPs analyzed in serum samples of 4,739 individuals in three subsamples of the National Health and Nutrition Examination Survey (NHANES) 2003-2004 (the last period with valid updated individual data for the compounds considered in the present study), we computed the number of POPs whose serum concentrations were above selected cutoff points. POPs included were 13 organochlorine compounds (OCs), 10 polybrominated diphenyl ethers (PBDEs), the polybrominated biphenyl (PBB) 153, 38 polychlorinated biphenyls (PCBs), 17 polychlorinated dibenzo-p-dioxins and dibenzofurans (PCDDs/Fs), and 12 perfluorinated compounds (PFCs). Over 13% of participants had ≥10 of the 37 most detected POPs each at a concentration in the top decile (P90). Over 30% of subjects with total toxic equivalency (TEQ) ≥P75, had ≥10 of 24 POPs not included in TEQ calculations at concentrations ≥P90. Compared to non-Hispanic whites, the adjusted odds ratio of having ≥10 of the 37 POPs at P90 was 9.2 for non-Hispanic blacks and 0.18 for Mexican Americans. Poverty, body mass index, age, and gender were also independently associated with having ≥10 POPs in the top decile. More than one tenth of the US population may have ≥10 POPs each at concentrations in the top decile. Such pattern is nine times more frequent in Non-Hispanic blacks and four times less frequent in Mexican Americans than in non-Hispanic whites.

Self-rated health and chronic conditions are associated with blood concentrations of persistent organic pollutants in the general population of Catalonia, Spain.

BACKGROUND: Self-rated health (SRH) is a powerful predictor of mortality, morbidity, and need for health services. SRH generally increases with educational level, and decreases with age, number of chronic conditions, and body mass index (BMI). Because human concentrations of most persistent organic pollutants (POPs) also vary by age, education, and BMI, and because of the physiological and clinical effects of POPs, we hypothesized that body concentrations of POPs are inversely associated with SRH. OBJECTIVES: To analyze the relation between serum concentrations of POPs and SRH in the general population of Catalonia, Spain, taking into account sociodemographic factors and BMI, as well as chronic health conditions and mental disorders, measured by the General Health Questionnaire-12 (GHQ-12). METHODS: POP serum concentrations were measured by gas chromatography with electron-capture detection in 919 participants of the Catalan Health Interview Survey. RESULTS: Individuals with higher concentrations of POPs had significantly poorer SRH; e.g., the median concentration of HCB in subjects with poor SRH was twice as high as in subjects with excellent SRH (366 ng/g vs. 169 ng/g, respectively; p-value<0.001). In crude models and in models adjusted for sex and BMI, the POPs-SRH association was often dose-dependent, and the likelihood of poor or regular SRH was 2 to 4-times higher in subjects with POP concentrations in the top quartile. In models adjusted for age or for chronic conditions virtually all ORs were near unity. No associations were found between POP levels and GHQ-12. CONCLUSIONS: Individuals with higher concentrations of POPs had significantly poorer SRH, an association likely due to age and chronic conditions, but not to sex, education, social class, BMI, or mental disorders.

Population variation in biomonitoring data for persistent organic pollutants (POPs): an examination of multiple population-based datasets for application to Australian pooled biomonitoring data.

BACKGROUND: Australian national biomonitoring for persistent organic pollutants (POPs) relies upon age-specific pooled serum samples to characterize central tendencies of concentrations but does not provide estimates of upper bound concentrations. This analysis compares population variation from biomonitoring datasets from the US, Canada, Germany, Spain, and Belgium to identify and test patterns potentially useful for estimating population upper bound reference values for the Australian population. METHODS: Arithmetic means and the ratio of the 95th percentile to the arithmetic mean (P95:mean) were assessed by survey for defined age subgroups for three polychlorinated biphenyls (PCBs 138, 153, and 180), hexachlorobenzene (HCB), p,p-dichlorodiphenyldichloroethylene (DDE), 2,2',4,4' tetrabrominated diphenylether (PBDE 47), perfluorooctanoic acid (PFOA) and perfluorooctane sulfonate (PFOS). RESULTS: Arithmetic mean concentrations of each analyte varied widely across surveys and age groups. However, P95:mean ratios differed to a limited extent, with no systematic variation across ages. The average P95:mean ratios were 2.2 for the three PCBs and HCB; 3.0 for DDE; 2.0 and 2.3 for PFOA and PFOS, respectively. The P95:mean ratio for PBDE 47 was more variable among age groups, ranging from 2.7 to 4.8. The average P95:mean ratios accurately estimated age group-specific P95s in the Flemish Environmental Health Survey II and were used to estimate the P95s for the Australian population by age group from the pooled biomonitoring data. CONCLUSIONS: Similar population variation patterns for POPs were observed across multiple surveys, even when absolute concentrations differed widely. These patterns can be used to estimate population upper bounds when only pooled sampling data are available.

Contamination from endocrine disrupters of the general population at low and high concentrations.

Analyses of the concentrations of a given environmental compound usually show that most citizens have much lower concentrations than a certain minority, whose members have high body concentrations. Surveys of human exposure to chemicals do not usually integrate the number of chemical compounds detected per person and the concentration of each compound. This leaves untested relevant exposure situations, for example, whether individuals with low concentrations of some compounds have high concentrations of the other compounds. On scientific grounds, it is puzzling that this possibility, arithmetically and conceptually rather simple, has seldom if ever been tested in studies based on a representative sample of the general population. A study based on a representative sample of the general population of Catalonia (Spain) (Porta, Pumarega, & Gasull, 2012), which integrated the number of compounds detected per person and the concentration of each compound, found that more than half of the population had concentrations in the top quartile of 1 or more of the 19 persistent toxic substances (PTS) (pesticides and polychlorinated biphenyls) analyzed. Significant subgroups of the population accumulated PTS mixtures at high concentrations. For instance, 48% of women 60-74 years had concentrations of 6 or more PTS in the top quartile; half of the entire population had levels of 1-5 PTS above 500 ng/g, and less than 4% of citizens had all PTS in the lowest quartile. Thus, PTS concentrations appear low in most of the population only when each individual compound is looked at separately. It is not accurate to state that most of the population has low concentrations of PTS. The assessment of mixture effects must address the fact that most individuals are contaminated by PTS mixtures made of compounds at both low and high concentrations.

Relative effects of educational level and occupational social class on body concentrations of persistent organic pollutants in a representative sample of the general population of Catalonia, Spain.

Scant evidence is available worldwide on the relative influence of occupational social class and educational level on body concentrations of persistent organic pollutants (POPs) in the general population. The objective was to analyse such influence in a representative sample of the general population of Catalonia, Spain. Participants in the Catalan Health Interview Survey aged 18-74 were interviewed face-to-face, gave blood, and underwent a physical exam. The role of age, body mass index (BMI), and parity was analysed with General Linear Models, and adjusted geometric means (GMs) were obtained. Crude (unadjusted) concentrations were higher in women and men with lower education, and in women, but not men, in the less affluent social class. After adjusting for age, in women there were no associations between POP levels and social class or education. After adjusting for age and BMI, men in the less affluent class had higher p,p'-DDE concentrations than men in class I (p-value=0.016), while men in class IV had lower HCB than men in the upper class (p-value<0.03). Also in contrast with some expectations, positive associations between education and POP levels were observed after adjusting for age and BMI in men; e.g., men with university studies had higher HCB concentrations than men with first stage of primary schooling (adjusted GM 153.9 and 80.5ng/g, respectively) (p-value<0.001). When education and social class were co-adjusted for, some positive associations with education in men remained statistically significant, whereas class remained associated only with p,p'-DDE. Educational level influenced blood concentrations of POPs more than occupational social class, especially in men. In women, POP concentrations were mainly explained by age/birth cohort, parity and BMI. In men, while concentrations were also mainly explained by age/birth cohort and BMI, both social class and education showed positive associations. Important characteristics of socioeconomic groups as age and BMI may largely explain crude differences among such groups in internal contamination by POPs. The absence of clear patterns of relationships between blood concentrations of POPs and indicators of socioeconomic position may fundamentally be due to the widespread, lifelong, and generally invisible contamination of human food webs. Decreasing historical trends would also partly explain crude socioeconomic differences apparently due to birth cohort effects.

Adipose tissue concentrations of persistent organic pollutants and prevalence of type 2 diabetes in adults from Southern Spain.

There is increasing evidence that environmental factors play an important role in the development of type 2 diabetes. Several persistent organic pollutants are suspected to contribute to the increasing prevalence and risk of type 2 diabetes. The aim of this study was to investigate the association of the body burden of three organochlorine pesticides and three polychlorinated biphenyls and the overall estrogenic activity with the risk of type 2 diabetes in a sample of adults from Southern Spain. Samples of adipose tissue and serum were obtained from 386 subjects undergoing non-cancer-related surgery and were extracted using validated methodologies. Residues of persistent organic pollutants were analyzed by means of high-resolution gas chromatography with a mass spectrometry detector in tandem mode. The overall estrogenicity of the adipose tissue extracts was measured by using the total effective xenoestrogen burden (TEXB) biomarker. Data on lifestyle, dietary habits, and health status were gathered from face-to-face interviews and clinical records. Statistical analyses were performed with unconditional logistic regression and different adjustment levels. In the models adjusted for adipose tissue origin, sex, age, and body mass index, the 2nd and 3rd tertiles of adipose tissue concentrations of p,p'-dichlorodiphenyldichloroethylene (p,p'-DDE) were positively associated with the risk of diabetes [odds ratios (95% confidence interval)=3.6 (0.8-17.3) and 4.4 (1.0-21.0), respectively]. A positive association with ß-hexachlorocyclohexane was also found when body mass index and adipose tissue origin were removed from the models, with odds ratios (95% confidence interval) of 3.3 (1.0-10.4) and 5.5 (1.7-17.3), for the 2nd and 3rd tertiles of exposure, respectively. In addition, a statistically significant interaction was observed between p,p'-DDE and body mass index, such that the risk of diabetes increased with tertiles of exposure in a linear manner in non-obese subjects but not in the obese, in whom an inverted U-shape pattern was observed.

Blood concentrations of persistent organic pollutants and prediabetes and diabetes in the general population of Catalonia.

The aim was to analyze the effects of body mass index (BMI), low-dose exposure, mixtures of persistent organic pollutants (POPs), and lipid adjustment on the relationship between POP concentrations and diabetes and prediabetes in the general adult population of Catalonia (Spain). Serum concentrations of POPs were measured by gas chromatography with electron-capture detection in 886 participants in a health interview survey. The highest concentrations of all POPs analyzed were found in subjects who had diabetes. Levels were also higher in individuals with prediabetes than in subjects without the disorder. In models adjusted by age, sex and BMI, the prevalence of diabetes and prediabetes increased in a dose-dependent manner across quartiles of PCBs 118, 138, 153, and 180, and HCB. When models were further adjusted for lipids, the associations were slightly lower and statistically significant, the ORs for the upper quartile ranging from 2.0 to 2.8 (all p-values for linear trend <0.05). Concentrations of p,p'-DDT, p,p'-DDE and ß-HCH were not associated with diabetes or prediabetes. Increasing concentrations of PCBs and HCB were positively associated with diabetes and prediabetes. Only part of the association was due to age and BMI. Findings support the hypothesis that exposure to POPs may be a diabetogenic factor in both obese and nonobese individuals.

Number of persistent organic pollutants detected at high concentrations in a general population.

BACKGROUND: Surveys of human exposure to environmental chemicals do not integrate the number of compounds detected per person and the concentration of each compound. This leaves untested relevant exposure scenarios, such as whether individuals with low concentrations of some compounds have high concentrations of the other compounds. OBJECTIVE: To analyze the number of persistent organic pollutants (POPs) detected at high concentrations. METHODS: Serum concentrations of 19 POPs were analyzed by gas chromatography with electron-capture detection in a representative sample of the general population of Catalonia, Spain (N=919). RESULTS: Over 58% of participants had concentrations in the top quartile of ≥1 of the eight most prevalent POPs, and 34% of ≥3 POPs. 83% of women 60 to 74 years old had concentrations of ≥3 POPs in the top quartile; 56% of women 60 to 74 years had p,p'-DDE, HCB and ß-HCH all in their respective top quartiles, and 48% had concentrations of ≥6 POPs in the top quartile. Over 30% of subjects had concentrations in the top decile of 1 to 5 of the eight most prevalent POPs. Half of the population had levels of 1 to 5 POPs >500 ng/g. Less than 4% had all eight POPs in the lowest quartile. CONCLUSIONS: More than half of the study population had concentrations in the top quartile of ≥1 POPs. Significant subgroups of the population accumulate POP mixtures at high concentrations. POP concentrations appear low in most of the population only when each individual compound is looked at separately.