Bisphenol A exposure affects specific gut taxa and drives microbiota dynamics in childhood obesity.

Cumulative xenobiotic exposure has an environmental and human health impact which is currently assessed under the One Health approach. Bisphenol A (BPA) exposure and its potential link with childhood obesity that has parallelly increased during the last decades deserve special attention. It stands during prenatal or early life and could trigger comorbidities and non-communicable diseases along life. Accumulation in the nature of synthetic chemicals supports the "environmental obesogen" hypothesis, such as BPA. This estrogen-mimicking xenobiotic has shown endocrine disruptive and obesogenic effects accompanied by gut microbiota misbalance that is not yet well elucidated. This study aimed to investigate specific microbiota taxa isolated and selected by direct BPA exposure and reveal its role on the overall children microbiota community and dynamics, driving toward specific obesity dysbiosis. A total of 333 BPA-resistant isolated species obtained through culturing after several exposure conditions were evaluated for their role and interplay with the global microbial community. The selected BPA-cultured taxa biomarkers showed a significant impact on alpha diversity. Specifically, Clostridium and Romboutsia were positively associated promoting the richness of microbiota communities, while Intestinibacter, Escherichia-Shigella, Bifidobacterium, and Lactobacillus were negatively associated. Microbial community dynamics and networks analyses showed differences according to the study groups. The normal-weight children group exhibited a more enriched, structured, and connected taxa network compared to overweight and obese groups, which could represent a more resilient community to xenobiotic substances. In this sense, subnetwork analysis generated with the BPA-cultured genera showed a correlation between taxa connectivity and more diverse potential enzymatic BPA degradation capacities.IMPORTANCEOur findings indicate how gut microbiota taxa with the capacity to grow in BPA were differentially represented within differential body mass index children study groups and how these taxa affected the overall dynamics toward patterns of diversity generally recognized in dysbiosis. Community network and subnetwork analyses corroborated the better connectedness and stability profiles for normal-weight group compared to the overweight and obese groups.

Levels of Bisphenol A and its analogs in nails, saliva, and urine of children: a case control study.

Introduction: A growing number of studies link the increase in overweight/obesity worldwide to exposure to certain environmental chemical pollutants that display obesogenic activity (obesogens). Since exposure to obesogens during the first stages of life has been shown to have a more intense and pronounced effect at lower doses, it is imperative to study their possible effects in childhood. The objective here was to study the association of Bisphenol A (BPA) and 11 BPA analogs in children, using three biological matrices (nails, saliva and urine), and overweight and obesity (n = 160). Methods: In this case-control study, 59 overweight/obese children and 101 controls were included. The measuring of Bisphenols in the matrices was carried out by ultra-high performance liquid chromatography coupled with triple quadrupole tandem mass spectrometry (UHPLC-MS/MS). Logistic regression was used to study the association between overweight/obesity and Bisphenol exposure. Results: The results suggested that BPF in nails is associated with overweight/ obesity in children (OR:4.87; p = 0.020). In saliva, however, the highest detected concentrations of BPAF presented an inverse association (OR: 0.06; p = 0.010) with overweight/obesity. No associations of statistical significance were detected between exposure to BPA or its other analogs and overweight/obesity in any of the biological matrices.

Association of genetic polymorphisms in detoxifying systems and urinary metal(loid) levels with excess body weight among Spanish children: A proof-of-concept study.

Exposure to metal(loid)s during critical developmental windows could result in permanent damage to the target organ system, increasing susceptibility to disease later in life. In view of the fact that metals(loid)s have been shown to work as obesogens, the aim of the present case-control study was to evaluate the modification effect of exposure to metal(loid)s on the association between SNPs in genes involved in metal(loid) detoxification and excess body weight among children. A total of 134 Spanish children aged 6-12 years old were included (88 controls and 46 cases). Seven SNPs (GSTP1 rs1695 and rs1138272; GCLM rs3789453, ATP7B rs1061472, rs732774 and rs1801243; and ABCC2 rs1885301) were genotyped on GSA microchips, and ten metal(loid)s were analysed in urine samples through Inductively coupled plasma mass spectrometry (ICP-MS). Multivariable logistic regressions were conducted to assess the genetic and metal exposures' main association and interaction effects. GSTP1 rs1695 and ATP7B rs1061472 showed significant effects on excess weight increase in those children carrying two copies of the risk G allele and being highly exposed to chromium (ORa = 5.38, p = 0.042, p interaction = 0.028 for rs1695; and ORa = 4.20, p = 0.035, p interaction = 0.012 for rs1061472) and lead (ORa = 7.18, p = 0.027, p interaction = 0.031 for rs1695, and ORa = 3.42, p = 0.062, p interaction = 0.010 for rs1061472). Conversely, GCLM rs3789453 and ATP7B rs1801243 appeared to play a protective role against excess weight in those exposed to copper (ORa = 0.20, p = 0.025, p interaction = 0.074 for rs3789453) and lead (ORa = 0.22, p = 0.092, p interaction = 0.089 for rs1801243). Our findings provide the first proof that interaction effects could exist between genetic variants within GSH and metal transporting systems and exposure to metal(loid)s, on excess body weight among Spanish children.

Effect of exposure to endocrine disrupting chemicals in obesity and neurodevelopment: The genetic and microbiota link.

Current evidence highlights the importance of the genetic component in obesity and neurodevelopmental disorders (attention-deficit hyperactivity disorder (ADHD), autism spectrum disorder (ASD) and intellectual disability (ID)), given that these diseases have reported an elevated heritability. Additionally, environmental stressors, such as endocrine disrupting chemicals (EDCs) have been classified as obesogens, neuroendocrine disruptors, and microbiota disrupting chemicals (MDCs). For this reason, the importance of this work lies in examining two possible biological mechanistic pathways linking obesity and neurodevelopmental/behavioural disorders: EDCs - gene and EDCs - microbiota interactions. First, we summarise the shared mechanisms of action of EDCs and the common genetic profile in the bidirectional link between obesity and neurodevelopment. In relation to interaction models, evidence from the reviewed studies reveals significant interactions between pesticides/heavy metals and gene polymorphisms of detoxifying and neurotransmission systems and metal homeostasis on cognitive development, ASD and ADHD symptomatology. Nonetheless, available literature about obesity is quite limited. Importantly, EDCs have been found to induce gut microbiota changes through gut-brain-microbiota axis conferring susceptibility to obesity and neurodevelopmental disorders. In view of the lack of studies assessing the impact of EDCs - gene interactions and EDCs - mediated dysbiosis jointly in obesity and neurodevelopment, we support considering genetics, EDCs exposure, and microbiota as interactive factors rather than individual contributors to the risk for developing obesity and neurodevelopmental disabilities at the same time.

Effects of genetic polymorphisms in body mass index according to dietary exposure to bisphenols and parabens.

A growing body of evidence supports that more than 900 single nucleotide polymorphisms (SNPs) and exposure to endocrine disrupting chemicals, such as bisphenols and parabens, are important contributors to the development of obesity. The aim of this study was to evaluate the way in which fat mass and obesity-associated gene (FTO) rs9939609 and leptin receptor (LEPR) rs9436303 variants contribute to variability in body mass index (BMI) according to estimated dietary exposure of bisphenols and parabens. This cross-sectional study included 101 Spanish participants (16-24 years). SNP genotyping assays were performed through quantitative PCRs (qPCRs) using Taqman® probes. Dietary exposure to bisphenols and parabens was calculated from food frequency questionnaire and chemical determination in food samples by ultra-high performance liquid chromatography-tandem mass spectrometry system. Linear regression models were conducted to address the association of genetic variants and BMI according to levels of bisphenols/parabens exposure. Risk G allele of LEPR rs9436303 was significantly positively associated with BMI (exp (ß) = 1.20, 95% CI: 1.04-1.38, p = 0.011). In participants highly exposed to bisphenols, the LEPR rs9436303 G allele was related to a significant increased BMI (exp (ß) = 1.27, 95% CI: 1.03-1.57, p = 0.024). A more relevant trend was observed with high exposure to parabens (exp (ß) = 1.33, 95% CI: 1.08-1.63, p = 0.009). We provide the first evidence that interaction between LEPR polymorphism and dietary intake of bisphenols and parabens may be responsible for an increased BMI, suggesting a potential effect in obesity. Moreover, we proposed LEPR rs9436303 as a genetic marker of susceptibility to excess weight induced by exposure.

Role of endocrine disrupting chemicals in children's neurodevelopment.

Environmental stressors, like endocrine disrupting chemicals (EDC), are considered important contributors to the increased rates of neurodevelopmental dysfunctions. Considering the cumulative research on adverse neurodevelopmental effects associated with prenatal exposure to EDC, the purpose of this study was to review the available limited literature about the effects of postnatal exposure to EDC on child neurodevelopment and behaviour. Despite widespread children's exposure to EDC, there are a limited number of epidemiological studies on the association of this exposure with neurodevelopmental disorders, in particular in the postnatal period. The available research suggests that postnatal EDC exposure is related to adverse neurobehavioral outcomes in children; however the underlying mechanisms of action remain unclear. Timing of exposure is a key factor determining potential neurodevelopmental consequences, hence studying the impact of multiple EDC co-exposure in different vulnerable life periods could guide the identification of sensitive subpopulations. Most of the reviewed studies did not take into account sex differences in the EDC effects on children neurodevelopment. We believe that the inclusion of sex in the study design should be considered as the role of EDC on children neurodevelopment are likely sex-specific and should be taken into consideration when determining susceptibility and potential mechanisms of action.

Metal exposure and biomarker levels among e-cigarette users in Spain.

The use of electronic cigarettes (e-cigarettes) has increased due to the belief that they are healthier than tobacco cigarettes. E-cigarettes contain a metallic heating coil (composed of Ni, Cr, Al and other metals) to heat a solution (commonly called e-liquid) and convert it into an aerosol. This aerosol is inhaled (vaped) by the users who can be potentially exposed to a wide variety of metals. We investigated the possible transfer of metals from the coil to the e-liquid and the generated aerosol, and how the exposure to this aerosol can increase metal body burden in e-cigarette users. We recruited 75 e-cigarette users (50 who only vaped and 25 dual users who vaped and smoked) and 25 controls who neither vaped nor smoked. E-liquid samples before (dispenser e-liquid) and after (tank e-liquid) being added to their devices were collected. Aerosol samples were collected using a condensation method. All participants provided urine and hair samples. All samples were analyzed for metals by ICP-MS. We observed higher metal concentrations in the aerosol and tank e-liquid (in contact with the coil) compared to the dispenser e-liquid (before contact with the coil). The median concentrations for some of the metals with the most remarkable increases in aerosol and tank e-liquid vs. dispenser e-liquid were 36.90 and 62.73 vs. 18.29 µg/kg for Al; 6.71 and 28.97 vs. 0.98 µg/kg for Cr; 91.39 and 414.47 vs. 1.64 µg/kg for Ni; 738.99 and 744.24 vs. 16.56 µg/kg for Zn; and 10.17 and 22.31 vs. 0.88 µg/kg for Pb. We also found detectable and potentially high concentrations of other metals such as Mn, Cu, Sb and Sn. In urine, increases in the median levels (µg/g creatinine) in vapers/duals vs. controls were observed for some metals, including Cr (0.34/0.28 vs. 0.20), Cu (1.72/2.36 vs. 1.46), Sn (0.26/0.31 vs. 0.18) and Pb (0.39/0.44 vs. 0.22). In hair, there were no differences in metal concentrations among the three groups. In conclusion, e-cigarettes are likely a source of metals such as Cr, Cu, Ni, Pb or Sn. These metals come from the device, likely the heating resistance, as their concentrations were low in the dispenser e-liquid and higher in the aerosol and the e-liquid left in the tank. Although the exposure to e-cigarette aerosol can have an influence in the body burden of metals, aerosol metal levels were not clearly associated with metal levels in biological samples such as urine or hair in e-cigarette users in this study.

Factors Associated with Exposure to Dietary Bisphenols in Adolescents.

Obesogenic endocrine-disrupting chemicals, such as bisphenol A (BPA) and its analogue bisphenol S (BPS), seem to play an important role in the development of obesity, although contradictory results have been reported. The aim of the present study was to conduct a gender analysis of the factors associated with exposure to dietary bisphenols in 585 Spanish adolescents. Dietary BPA and BPS exposure was assessed using a food frequency questionnaire. Foods and macronutrients accounting for more than 95% of energy intake were selected for analysis. Stepwise regression was used to estimate the foods that most contributed to dietary bisphenol exposure in the sample. Gender-related factors associated with greater dietary bisphenol exposure were evaluated using multivariate logistic regression models. Canned tuna was the main dietary source of BPA and BPS in both adolescent boys and girls. Overweight/obese girls showed a higher risk of high dietary exposure to BPA (odds ratio (OR): 3.38, 95% confidence interval (CI): 1.25-9.07) and total bisphenols (OR: 2.81, 95% CI: 1.03-7.67) in comparison with girls with a BMI lower than 25 kg/m2. Present results indicate a positive association of dietary exposure to both total bisphenols and BPA with being overweight/obese in adolescent girls.

Presence of Parabens and Bisphenols in Food Commonly Consumed in Spain.

Given the widespread use of bisphenols and parabens in consumer products, the assessment of their intake is crucial and represents the first step towards the assessment of the potential risks that these compounds may pose to human health. In the present study, a total of 98 samples of food items commonly consumed by the Spanish population were collected from different national supermarkets and grocery stores for the determination of parabens and bisphenols. Our analysis demonstrated that 56 of the 98 food samples contained detectable levels of parabens with limits of quantification (LOQ) between 0.4 and 0.9 ng g-1. The total concentration of parabens (sum of four parabens: ∑parabens) ranged from below the LOQ to 281.7 ng g-1, with a mean value of 73.86 ng g-1. A total of 52% of the samples showed detectable concentrations of bisphenols. Bisphenol A (BPA) was the most frequently detected bisphenol in the food samples analysed, followed by bisphenol S (BPS) and bisphenol E (BPE). Bisphenol AF (BPAF), bisphenol B (BPB) and bisphenol P (BPP) were not found in any of the analysed samples. LOQ for these bisphenols were between 0.4 and 4.0 ng g-1.

Bisphenol A Analogues in Food and Their Hormonal and Obesogenic Effects: A Review.

Bisphenol A (BPA) is the most well-known compound from the bisphenol family. As BPA has recently come under pressure, it is being replaced by compounds very similar in structure, but data on the occurrence of these BPA analogues in food and human matrices are limited. The main objective of this work was to investigate human exposure to BPA and analogues and the associated health effects. We performed a literature review of the available research made in humans, in in vivo and in vitro tests. The findings support the idea that exposure to BPA analogues may have an impact on human health, especially in terms of obesity and other adverse health effects in children.

Adherence to Mediterranean diet and risk of prostate cancer.

In Europe, countries following the traditional Mediterranean Diet (MeDi), particularly Southern European countries, have lower prostate cancer (PCa) incidence and mortality compared to other European regions. In the present study, we investigated the association between the MeDi and the relative risk of PCa and tumor aggressiveness in a Spanish population. Among individual score components, it has been found that subjects with PCa were less likely to consume olive oil as the main culinary fat, vegetables, fruits and fish than those without. However, these differences were not statistically significative. A high intake of fruit, vegetables and cooked tomato sauce Mediterranean style (sofrito) was related to less PCa aggressiveness. Results showed that there are no differences in the score of adherence to the Mediterranean dietary patterns between cases and controls, with mean values of 8.37 ± 1.80 and 8.25 ± 2.48, respectively. However, MeDi was associated with lower PCa agressiveness according to Gleason score. Hence, relations between Mediterranean dietary patterns and PCa are still inconclusive and merit further investigations. Further large-scale studies are required to clarify the effect of MeDi on prostate health, in order to establish the role of this diet in the prevention of PCa.

Bioactive compounds of the Mediterranean diet and prostate cancer.

OBJECTIVE: The purpose of this review is to examine the evidence on the effects of bioactive constituents of the Mediterranean diet (MeDi) on prostate cancer (PCa) risk. METHODS: The search for articles came from extensive research in the following databases: PubMed, Scopus, and Web of Science. We used the search terms "Mediterranean diet," "lycopene," "vitamin E," "vitamin C," "Selenium," "resveratrol," "prostate cancer," and combinations, such as "lycopene and prostate cancer" or "resveratrol and prostate cancer." RESULTS: Numerous studies investigating the effect of various dietary nutrients on PCa have suggested that selenium is probably the most promising. Several studies reported reduced PCa risk associated with vitamin C and E intake, while other studies reported no association. Lycopene inhibits cell proliferation and inducts apoptosis, thus protecting against cancer. Also, it has been found in various in vivo and in vitro studies that resveratrol, inhibits PCa development. CONCLUSIONS: The high content of bioactive phytochemicals in the MeDi is of particular interest in the prevention of PCa. Further large-scale studies are required to clarify the effect of MeDi bioactive compounds on prostate health, in order to establish the role of this diet in the prevention of PCa.

Rapid determination of quetiapine in blood by gas chromatography-mass spectrometry. Application to post-mortem cases.

A simple, fast and sensitive method for the determination of quetiapine in human blood has been developed and validated. The method involved a basic liquid-liquid extraction procedure and subsequent analysis by gas chromatography-mass spectrometry, previous derivatization with bis(trimethylsilyl)-trifluoro-acetamide and chorotrimethylsilane (99 : 1). The methods of validation included linearity with a correlation coefficient > 0.99 over the range 0.02-1 µg ml(-1), intra- and interday precision (always < 12%) and accuracy (mean relative error always < 12%) to meet the bioanalytical acceptance criteria. The limit of detection was 0.005 µg ml(-1). The procedure was further applied to post mortems from the Institute of Legal Medicine, University of Santiago de Compostela.

Mediterranean diet adherence and prostate cancer risk.

BACKGROUND: Countries following the traditional Mediterranean Diet, particularly Southern European countries, have lower prostate cancer incidence and mortality compared to other European regions. The beneficial effect has been attributed to a specific eating pattern. OBJECTIVE: The purpose of this review is to examine the evidence to date on the effects of adherence to a Mediterranean Diet on prostate cancer risk; and to identify which elements of the Mediterranean diet are likely to protect against prostate cancer. METHODS: The search for articles came from extensive research in the following databases: PubMed, Scopus and Web of Science. We used the search terms "Mediterranean diet", "adherence", "fruit and vegetable", "olive oil", "fish" "legume", "cereal" "alcohol" "milk", "dairy product","prostate cancer", and combinations, such as "Mediterranean diet and prostate cancer" or "Olive oil and prostate cancer". RESULTS: There is strong evidence supporting associations between foods that are typical of a Mediterranean eating pattern and reduced prostate cancer risk. However, there are few studies that have assessed the effect of the Mediterranean diet on cancer prostate incidence. Recent data do not support associations to adherence to a Mediterranean Diet and risk of prostate cancer or disease progression. However, Mediterranean eating pattern after diagnosis of nonmetastatatic cancer was associated with lower overall mortality. CONCLUSION: Further large-scale studies are required to clarify the effect of Mediterranean diet on prostate health, in order to establish the role of this diet in the prevention of prostate cancer.

Introducción: Los países del sur de Europa, tienen una menor incidencia y mortalidad por cáncer de próstata en comparación con otras regiones europeas. Este efecto beneficioso se ha atribuido a un patrón de alimentación específica. Objetivo: El objetivo de esta revisión es examinar la evidencia sobre los efectos de la adhesión a la dieta mediterránea en el riesgo de cáncer de próstata; e identificar que componentes de la dieta mediterránea protegen contra el cáncer de próstata. Métodos: Se realizó una búsqueda en la literatura científica utilizando las siguientes base de datos: PubMed, Scopus and Web of Science. Utilizamos los términos de búsqueda "dieta mediterránea", "adhesión", "frutas y verduras", "aceite de oliva", "pescado" "legumbres", "cereal" "alcohol" "leche", "producto lácteo", "cáncer de próstata", y combinaciones, tales como"dieta mediterránea y cáncer de próstata "o" aceite de oliva y cáncer de próstata ". Resultados: Existe una fuerte evidencia que soporta una asociación entre alimentos que son típicos de un patrón de alimentación mediterránea y un menor riesgo de cáncer de próstata. Sin embargo, son pocos los estudios que han evaluado el efecto de la dieta mediterránea sobre la incidencia del cáncer de próstata. Los datos recientes no apoyan una asociación entre el seguimiento de este tipo de dieta y el riesgo de cáncer de próstata o su progresión. Sin embargo, un patrón de alimentación mediterránea después del diagnóstico de cáncer no metastásico se ha asociado con una disminución de la mortalidad global. Conclusión: Se requieren más estudios a gran escala para aclarar el efecto de la dieta mediterránea sobre la salud prostática, con el fin de establecer su papel en la prevención de cáncer de próstata.

Urinary levels of arsenic and heavy metals in children and adolescents living in the industrialised area of Ria of Huelva (SW Spain).

The Ria of Huelva (south-west Spain) is a highly polluted estuary as a consequence of long-term mining and industrial activities. Between 2003 and 2004, we conducted a biomonitoring study of exposure to arsenic and some heavy metals (cadmium, chromium, copper and nickel) in urine samples of a representative sample (n=227) of children and adolescents residing in this area, and of a reference group of 196 children and adolescents living in other less industrialised areas of Andalusia (south Spain). We also assessed the determinants of the variability in urinary metals within the population of the Ria of Huelva. There were no significant differences in the concentration of metal compounds between the two groups with the exception of Cd levels, which were significantly higher in the reference group. Levels of the five metal ions in both groups were generally within the range of values reported by other biomonitoring studies for general children population, although mean Cd levels tended to be higher as compared to other European studies. Among the population of the Ria of Huelva, the main determinants of the interindividual variation in urinary metals were age, sex, area of residence, and frequency of intake of certain food items (mainly fish and shellfish). Overall, results suggest that living in the Ria of Huelva is not increasing current levels of exposure to certain metals among children and adolescents above those found in other urban areas of Andalusia.

Interaction between human serum esterases and environmental metal compounds.

Paraoxonase-1 (PON1) and cholinesterase (BChE) are two of the major human serum esterases. Although most of variation in PON1 activity results from genetic factors, there is growing evidence that environmental chemicals also modulate its activity. The aim of this study was to investigate whether environmental exposure to metal compounds has any influence on those esterases. A cross-sectional study was conducted in a representative sample of the general population of Andalusia, South of Spain. PON1 activity against different substrates (paraoxon, phenylacetate, diazoxon and dihydrocoumarin) and BChE were measured in serum from 536 healthy subjects. Potential associations of these esterases with metal compounds, age, sex and body mass index as well as life-style habits (smoking, alcohol drinking and food habits) were explored. Multiple linear regression analysis showed that blood lead levels were significantly associated with increased PON1 in serum regardless of the substrate used for the assay. Mercury also showed a significant and direct association with PON1 towards paraoxon and phenylacetate. In turn, cadmium and zinc levels were significantly associated with a decreased PON1 activity (zinc was associated with all PON1 activities and cadmium with PON1 towards paraoxon and diazoxon). Arsenic, nickel and manganese failed to be significantly associated with any of the PON1 activities assayed. PON1 192R alloform predicted significantly higher levels of arsenic and lead. BChE, however, was inversely associated with serum levels of manganese and zinc. These results suggest that PON1 and BChE activities are modulated by background exposure to metal compounds, which may have implications in public health given the defensive role played by both enzyme proteins against environmental toxicants. The potential underlying mechanisms merit further investigation.

Changes in antioxidant enzymes in humans with long-term exposure to pesticides.

Different pesticides, including organophosphates (OPs), have been reported to induce oxidative stress due to generation of free radicals and alteration in antioxidant defence mechanisms. In this study, a cohort of 81 intensive agriculture workers (pesticide sprayers) was assessed twice during the course of a spraying season for changes in erythrocyte antioxidant enzymes. Acetylcholinesterase (AChE) was used as a reference biomarker. Sprayers presented lower levels of superoxide dismutase (SOD) and glutathione reductase (GR) as compared to controls independently of age, BMI, smoking habit or alcohol consumption. A positive correlation between SOD and AChE was observed at the high exposure period. Those individuals with a decrease in AChE greater than 15% exhibited lower SOD and catalase (CAT) activities at the same period. Glutathione peroxidase (GPx) and glucose-6-phosphate dehydrogenase (G6PDH) remained unaffected in the exposed population. Paraoxonase (PON1) polymorphism influenced erythrocyte CAT and GR, as subjects with the R allele presented lower CAT and higher GR levels. Whether or not the decreased enzyme activities found in this study are linked to the adverse health effects related to chronic pesticide toxicity (in which oxidative damage plays a pathophysiological role, such as cancer or neurodegenerative disorders) is an attractive hypothesis that warrants further investigation.

Heavy metal concentrations in the general population of Andalusia, South of Spain: a comparison with the population within the area of influence of Aznalcóllar mine spill (SW Spain).

Levels of metalloids (As - urine) and heavy metals (Hg - urine, Cd - whole blood and Zn - serum) were determined by atomic absorption spectrometry in 601 subjects living in the area affected by the Aznalcóllar mine spill (SW, Spain) and compared with those of a representative sample (960 subjects) selected from the Andalusian community (non-affected area), southern Spain. The characteristic parameters of the analytical method including uncertainty were determined for each metal. Potential associations of metal concentration with age, sex and body mass index as well as life-style habits (smoking, alcohol consumption and food habits) were explored. Concentrations of all the metals studied were statistically higher in the population of the affected area with respect to that of the non-affected area in Andalusia, although levels were always lower or similar to the values reported for the general population and below occupational reference limits. In conclusion, there is a lack of evidence that the spill had any incidence on human health in the population living in the affected area. There are few references in scientific literature reporting values from large series of samples, and hence our data could be useful for further studies.

Influence of exposure to pesticides on serum components and enzyme activities of cytotoxicity among intensive agriculture farmers.

Although the effects of acute pesticide poisoning are well known for the pesticides most currently used, hardly any data exist on health effects after long-term low-dose exposures. Major unresolved issues include the effect of moderate exposure in the absence of poisoning. The increased utilization of pesticides other than organophosphates makes it even more difficult to find associations. In this study a cohort of 106 intensive agriculture workers were assessed twice during the course of a spraying season for changes in serum biochemistry, namely enzymes reflecting cytotoxicity (AST, ALT, LDH, CK, and amino-oxidase) and other biochemical parameters, such as markers of nephrotoxicity (urea, creatinine) and lipid profile (cholesterol and triglycerides). Several criteria for estimating pesticide exposure were used, the most important one being serum cholinesterase depression greater than 25% from baseline to peak exposure. Our results revealed an association of pesticide exposure with changes in AST (increased activity), LDH, and amino-oxidase (decreased activity) as well as with changes in serum creatinine and phosphorus (lower and higher levels, respectively). These results provide support for a very slight impairment of the liver function, but overall these findings are consistent with no clinically significant hepatotoxicity. Intriguingly, paraoxonase-1 R allele was found to be an independent predictor of higher rates of AST and lower rates of amino-oxidase, so that it may play a supporting role as an individual marker of susceptibility on pesticide-induced health effects. In conclusion, different biomarkers might be used to detect early biochemical effects of pesticides before adverse clinical health effects occur.

Changes in erythrocyte enzymes in humans long-term exposed to pesticides: influence of several markers of individual susceptibility.

Changes in erythrocyte delta-aminolevulinic acid dehydratase (ALA-D) have been reported after exposure to different pesticides, including organophosphates and paraquat. In this study, we have determined ALA-D in 135 pesticide applicators (sprayers) from an intensive agriculture setting at two periods with different pesticide exposure. Acetylcholinesterase (AChE) was used as a reference biomarker. The effects of the combined polymorphism of enzymes involved in the detoxification of pesticides (paraoxonase (PON1), benzoylcholinesterase (BChE), and glutathione S-transferase (GSTM1 and GSTT1)) on the level of the target erythrocyte enzymes were also studied as biomarkers of individual susceptibility. Sprayers presented significant lower levels of ALA-D and AChE than controls (41.3% and 14.5%, respectively) at the high exposure period. When all biomarkers of individual susceptibility to pesticides were considered at the same time, the GSTT1 null allele determined higher ALA-D and AChE activities at the period of high exposure to pesticides. PON1 R allele in turn determined lower AChE activity at the low exposure period. Null genotype for both GST subclasses (GSTM1 and GSTT1) was found to be the unique independent predictor of pesticide-related symptomatology. Interestingly, sprayers were consistently underrepresented among carriers of "unfavourable" BChE variants. In conclusion, ALA-D appears to be an important biological indicator of pesticide exposure and PON1 and GSTT1 are relevant determinants of susceptibility to chronic pesticide poisoning.