Renal tubular dysfunction in greenhouse farmers exposed to pesticides unveiled by a panel of molecular biomarkers of kidney injury.

Growing evidence suggests that chronic exposure to pesticides may cause adverse effects on the health of the exposed population leading to organ-specific toxicity, including kidney damage. Traditional markers used to assess renal function (glomerular filtration rate (GFR), and serum creatinine and cystatin C -Cys-C-) are inadequate to evaluate a potential subclinical renal impairment linked to occupational exposure to pesticides, since levels above the upper limit of normal only occur when renal damage is very extensive. The use of more sensitive biomarkers is therefore needed. This study investigated novel urinary biomarkers of kidney function (microalbuminuria, osteopontin (OPN), trefoil factor 3 (TFF3), ß-2-microglobulin, neutrophil gelatinase-associated lipocalin (NGAL), and Cys-C), together with the aforementioned traditional serum biomarkers, to assess potential kidney damage in farmers exposed to pesticides in an intensive agriculture setting. The study population consisted of 175 greenhouse workers and 91 healthy control subjects from Almeria (Southeastern Spain), a major hub of greenhouse agriculture. Data were collected at two different time-points of the same crop season: a period with greater pesticide use (high exposure period) and another with lower pesticide use (low exposure period). Significantly higher urinary levels of OPN and TFF3 were found in greenhouse workers than in controls, and in the high pesticide exposure period compared to that of low exposure. These changes suggest a subclinical tubular damage linked to pesticide exposure. In contrast, microalbuminuria, GFR, serum creatinine and Cys-C failed to be associated with pesticide exposure, suggesting that glomerular function was spared. Increased OPN and TFF3 levels over time may suggest a gradual progression from tubular dysfunction to chronic kidney disease in the exposed population.

Occupational exposure to pesticides as a potential risk factor for epilepsy.

Epilepsy is a chronic neurological disorder in which brain activity becomes abnormal, causing seizures. In a previous study we found that environmental exposure to pesticides was associated with a greater risk of epilepsy. The present study examined possible occupational risk factors that may contribute to the occurrence of epilepsy in farmers and pesticide applicators (sprayers). A case-referent study was conducted on 19,704 individuals over a 17-year study period (2000-2016). Epilepsy cases (n = 5091) were collected from Hospital records and referents (non-epilepsy cases, n = 14.613) from the Centre for Prevention of Occupational Risks, both from Almería (South-Eastern Spain). A significant increased risk of having epilepsy was found in farmers working in intensive agriculture (high-yield greenhouse crops) compared to extensive agriculture (open-air crops). The risk was greater for farmers residing in rural areas with high pesticide use (intensive farming crops in plastic greenhouses) and for those not wearing protective gloves. As for sprayers, the greatest risk of epilepsy was observed in those not wearing face mask, and in those living in areas with high pesticide use (greenhouse intensive agriculture). Overall, this study supports previous findings on the association between epilepsy and pesticide exposure in the general population, and extends the risk to farmers occupationally exposed to pesticides, mainly those engaged in intensive agriculture.

Evaluation of conventional and non-conventional biomarkers of liver toxicity in greenhouse workers occupationally exposed to pesticides.

The liver plays a prominent role in maintenance of homeostasis and is the major organ for xenobiotic metabolism, including pesticides. Conventional liver function tests are widely used to assess hepatocellular and biliary system dysfunction by measuring serum levels of aminotransferases (ALT, AST) and cholestasis enzymes (alkaline phosphatase -ALP- and γ-glutamyl transferase -GGT-), respectively. Although these tests are not entirely specific for liver damage, their specificity increases when measured concurrently, but still have limited usefulness to predict early liver dysfunction. Hence, non-conventional biomarkers may have a better performance for the early detection of biochemical hepatotoxicity with a greater specificity and sensitivity. A cross-sectional study with a follow-up component was conducted on 175 greenhouse workers regularly exposed to pesticides under integrated production system, and 91 controls living in the same geographical area. All individuals were evaluated for conventional (ALT, AST, ALP, GGT) and non-conventional biomarkers of hepatotoxicity (ornithine transcarbamylase (-OTC-), Arginase-1 -ARG1- and glutathione S-transferase alpha -GSTα-) over two periods of the same crop season, one of high pesticide exposure and other of low exposure. A slight increase in AST was observed in greenhouse workers relative to controls, suggestive of subtle hepatocellular toxicity. Although ALP, ARG1 and GST-α levels were decreased in greenhouse workers, this might be related to a potential homeostatic mechanism that regulates their expression. Altogether, these findings do not represent unambiguous evidence of liver dysfunction (e.g., hepatocellular or biliary system impairment) but may be the result of the low-toxicity pesticides used by greenhouse workers.

Virgin Olive Oil and Health: Summary of the III International Conference on Virgin Olive Oil and Health Consensus Report, JAEN (Spain) 2018.

The Mediterranean diet is considered as the foremost dietary regimen and its adoption is associated with the prevention of degenerative diseases and an extended longevity. The preeminent features of the Mediterranean diet have been agreed upon and the consumption of olive oil stands out as the most peculiar one. Indeed, the use of olive oil as the nearly exclusive dietary fat is what mostly characterizes the Mediterranean area. Plenty of epidemiological studies have correlated that the consumption of olive oil was associated with better overall health. Indeed, extra virgin olive oil contains (poly)phenolic compounds that are being actively investigated for their purported biological and pharma-nutritional properties. On 18 and 19 May 2018, several experts convened in Jaen (Spain) to discuss the most recent research on the benefits of olive oil and its components. We reported a summary of that meeting (reviewing several topics related to olive oil, not limited to health) and concluded that substantial evidence is accruing to support the widespread opinion that extra virgin olive oil should, indeed, be the fat of choice when it comes to human health and sustainable agronomy.

Environmental exposure to pesticides and risk of thyroid diseases.

Occupational and environmental exposure to pesticides has been associated with thyroid dysfunction, particularly changes in circulating thyroid hormone levels (T3, T4) and thyroid stimulating hormone (TSH). This study assessed the association between environmental exposure to pesticides and the risk of developing thyroid diseases. A population-based case-control study was carried out among Spanish populations living in areas categorized as of high or low pesticide use according to agronomic criteria, which were used as surrogates for environmental exposure to pesticides. The study population consisted of 79.431 individuals diagnosed with goiter, thyrotoxicosis, hypothyroidism, and thyroiditis (according to the International Classification of Diseases, Ninth Revision) and 1.484.257 controls matched for age, sex and area of residence. Data were collected from computerized hospital records for the period 1998 to 2015. Prevalence rates and risk of having thyroid diseases were significantly higher in areas with higher pesticide use, with a 49% greater risk for hypothyroidism, 45% for thyrotoxicosis, 20% for thyroiditis and 5% for goiter. Overall, this study indicates an association between increased environmental exposure to pesticides as a result of a greater agricultural use and diseases of the thyroid gland, thus supporting and extending previous evidence. This study also provides support to the methodology proposed for real-life risk simulation, thus contributing to a better understanding of the real life threat posed by exposure to multiple pesticides from different sources.

Association between environmental exposure to pesticides and epilepsy.

There is increasing evidence of an association between long-term environmental exposure to pesticides and neurodegenerative disorders; however, the relationship with epilepsy has not been addressed thus far. This study was aimed at determining the prevalence and risk of developing epilepsy among people from South-East Spain living in areas of high vs. low exposure to pesticides based on agronomic data. The study population consisted of 4007 subjects with a diagnosis of epilepsy and 580,077 control subjects adjusted for age, sex and geographical area. Data were collected from hospital records of the Spanish health care system (basic minimum dataset) between the years 1998 and 2010. The prevalence of epilepsy was significantly higher in areas of greater pesticide use relative to areas of lesser use. Overall, an increased risk of epilepsy was observed in the population living in areas of high vs. low use of pesticides (OR: 1.65; p < 0.001). Although this study was exploratory in nature, the results suggest that environmental exposure to pesticides might increase the risk of having epilepsy.

Biomarkers of oxidative stress in blood of workers exposed to non-cholinesterase inhibiting pesticides.

In occupational settings workers are often exposed to pesticides at relatively high doses compared to environmental exposures. Long-term exposure to pesticides has been associated with numerous adverse health effects in epidemiological studies, and oxidative stress is often claimed as one of the underlying mechanisms. In fact, different pesticides have been reported to induce oxidative stress due to the generation of free radicals and/or alteration in antioxidant defense enzymes. The present study examined greenhouse workers regularly exposed to diverse pesticides under integrated production system, and a group of controls of the same geographic area without any chemical exposure. Two different periods of the same crop season were assessed, one of high exposure (with greater use of pesticides) and other of low exposure (in which a less use of these compounds was made). Non-specific biomarkers of oxidative stress, e.g. thiobarbituric acid reactive substances (TBARS), ferric reducing ability of serum (FRAS), total thiol groups (SHT), gamma-glutamyl transpeptidase (GGT) and paraoxonase-1 (PON1) were measured in serum samples from all study subjects, alongside erythrocyte acetylcholinesterase (AChE). Results are suggestive of a mild increase in oxidative stress associated with pesticide exposure, which was compensated by an adaptive response to raise the antioxidant defenses and thus counter the detrimental effects of sustained oxidative stress. This response led to significantly increased levels of FRAS, SHT and PON1 in greenhouse workers relative to controls. Furthermore, AChE was decreased likely as a result of oxidative stress as workers did not use organophosphate insecticides.

Percepciones y uso del cigarrillo electrónico en estudiantes universitarios / Perceptions and use of the e-cigarette among university students

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Association of reproductive disorders and male congenital anomalies with environmental exposure to endocrine active pesticides.

There is growing evidence that environmental exposure to pesticides may increase the risk of developing reproductive and developmental disorders. This study determined the prevalence and risk of developing gestational disorders and male congenital genitourinary malformations in areas with distinct exposure to pesticides, many of them with potential endocrine disrupting properties. A population-based case-control study was carried out on pregnant women and male children living in ten health districts of Andalusia classified as areas of high and low environmental exposure to pesticides according to agronomic criteria. The study population included 45,050 cases and 950,620 controls matched for age and health district. Data were collected from computerized hospital records between 1998 and 2005. Prevalence rates and risk of miscarriage, low birth weight, hypospadias, cryptorchidism and micropenis were significantly greater in areas with higher use of pesticides in relation to those with lower use, thus supporting and extending previous information.

Activity and determinants of cholinesterases and paraoxonase-1 in blood of workers exposed to non-cholinesterase inhibiting pesticides.

Pesticide exposure has been associated with different adverse health effects which may be modulated to some extent by paraoxonase-1 (PON1) activity and genetic polymorphisms. This study assessed seasonal variations in PON1 activity (using paraoxon -POase-, phenylacetate -AREase-, diazoxon -DZOase- and dihydrocoumarin -DHCase- as substrates), erythrocyte acetylcholinesterase (AChE) and plasma cholinesterase (using butyrylthiocholine -BuChE- and benzoylcholine -BeChE- as substrates. The study population consisted of intensive agriculture workers regularly exposed to pesticides other than organophosphates and non-exposed controls from Almería (Southeastern Spain). The effect of common genetic polymorphisms of PON1 and BCHE on paraoxonase-1 and cholinesterase activities toward different substrates was also assessed. Linear mixed models were used to compare esterase activities in agricultural workers and control subjects over the two study periods (high and low exposure to pesticides). The significant decrease in AChE and increase in BuChE and BeChE activities observed in workers with respect to control subjects was attributed to pesticide exposure. Workers also had higher levels of AREase, DZOase and, to a lesser extent, of POase, but showed decreased DHCase activity. While PON1 Q192R and PON1 -108C/T gene polymorphisms were significantly associated with all PON1 activities, PON1 L55M showed a significant association with AREase, DZOase and DHCase. BCHE-K (Karlow variant) was significantly associated with lower BeChE activity (but not with BuChE) and BCHE-A (atypical variant) showed no significant association with any cholinesterase activity. These findings suggest that increased PON1, BuChE and BeChE activities in exposed workers might result from an adaptive response against pesticide exposure to compensate for adverse effects at the biochemical level. This response appears to be modulated by PON1 and BCHE gene polymorphisms.

Occupational pesticide exposure and adverse health effects at the clinical, hematological and biochemical level.

AIMS: Although epidemiological studies have investigated associations between occupational pesticide exposures and different adverse health outcomes, they have rarely assessed individuals at two time-points of a same crop season with different pesticide use. MATERIAL AND METHODS: Clinical symptoms, physical examination signs, hematological and clinical chemistry parameters were measured in 189 intensive agriculture workers and 91 healthy control subjects from Almeria coastline (Southeastern Spain) to evaluate potential effects of pesticide exposure. KEY FINDINGS: Greenhouse workers showed an increased risk of ocular and skin signs relative to controls at the period of high pesticide exposure (OR: 4.80 and 2.87, respectively); however, no differences were observed for clinical symptoms. A greater risk for ECG changes (OR: 3.35) and altered spirometry (OR: 5.02) was found at the period of low exposure. Erythrocyte acetylcholinesterase was significantly decreased in greenhouse workers relative to controls in both periods. Assessment of hematological parameters revealed increased counts of erythrocytes, leukocytes, platelets and hemoglobin in greenhouse workers relative to controls, and also in the period of high versus low pesticide exposure. Changes in clinical chemistry parameters included decreased levels of glucose, creatinine, total cholesterol, triglyceride and alkaline phosphatase in greenhouse workers relative to controls; however, these parameters were raised in the period of high versus low pesticide exposure. SIGNIFICANCE: These findings suggest that chronic occupational exposure to pesticides of lower toxicity than former compounds under integrated production systems elicit mild toxic effects, particularly targeting the skin and eyes, as well as subtle subclinical (biochemical) changes of unknown long-term consequences.

Pre- and postnatal exposures to pesticides and neurodevelopmental effects in children living in agricultural communities from South-Eastern Spain.

BACKGROUND: Childrens exposure to neurotoxic compounds poses a major problem to public health because oftheir actively developing brain that makes them highly vulnerable. However, limited information is available on neuropsychological effects in children associated with pre- and postnatal exposures to pesticides. OBJECTIVE: To evaluate the association between current and pre- and postnatal exposures to pesticides and their effects on neurodevelopment in children aged 6­11 years living in agricultural communities from South-Eastern Spain. METHODS: An ambispective study was conducted on 305 children aged 6­11 years randomly selected from public schools of the study area. Current exposure to organophosphate pesticides was assessed measuring children's urinary levels of dialkylphosphates (DAPs). Both prenatal and postnatal residential exposure to pesticides was estimated by developing a geographical information system (GIS) technology-based index that integrated distance-weighted measure of agricultural surface, time-series of crop areas per municipality and year, and land-use maps. Neuropsychological performance was evaluated with the Wechsler Intelligence Scale for Children-Fourth Edition (WISC-IV). The association of pre- and postnatal and current pesticide exposure with WISC-IV scale scores was assessed using multivariate linear regression models and generalized estimating equation (GEE) models, respectively. RESULTS: Greater urinary DAP levels were associated with a poorer performance on intelligence quotient and verbal comprehension domain, with effects being more prominent in boys than in girls. The influence of an increase in 10 ha per year in crop surface around the child's residence during the postnatal period was associated with decreased intelligence quotient, processing speed and verbal comprehension scores. As regards prenatal exposure to pesticides, a poor processing speed performance was observed. These effects were also more prominent in boys than in girls. CONCLUSIONS: Our results suggest that postnatal exposure to pesticides can negatively affect children's neuropsychological performance. Prenatal exposure was weakly associated to neurodevelopment impairment.

Environmental exposure to pesticides and cancer risk in multiple human organ systems.

There is growing evidence on the association between long-term exposure to pesticides in occupational settings and an elevated rate of chronic diseases, including different types of cancer. However, data on non-occupational exposures are scarce to draw any conclusion. The objective of this study was to investigate the putative associations of environmental pesticide exposures in the general population with several cancer sites and to discuss potential carcinogenic mechanisms by which pesticides develop cancer. A population-based case-control study was conducted among people residing in 10 Health districts from Andalusia (South Spain) to estimate the risk of cancer at different sites. Health districts were categorized into areas of high and low environmental pesticide exposure based on two quantitative criteria: number of hectares devoted to intensive agriculture and pesticide sales per capita. The study population consisted of 34,205 cancer cases and 1,832,969 age and health district matched controls. Data were collected by computerized hospital records (minimum dataset) between 1998 and 2005. Prevalence rates and the risk of cancer at most organ sites were significantly higher in districts with greater pesticide use related to those with lower pesticide use. Conditional logistic regression analyses showed that the population living in areas with high pesticide use had an increased risk of cancer at all sites studied (odds ratios between 1.15 and 3.45) with the exception of Hodgkin's disease and non-Hodgkin lymphoma. The results of this study support and extend previous evidence from occupational studies indicating that environmental exposure to pesticides may be a risk factor for different types of cancer at the level of the general population.

Pesticide exposure and genetic variation in xenobiotic-metabolizing enzymes interact to induce biochemical liver damage.

Metabolic activation of pesticides in the liver may result in highly reactive intermediates capable of impairing various cellular functions. Nevertheless, the knowledge about the effect of pesticide exposure on liver function is still limited. This study assessed whether exposure to pesticides elicits early biochemical changes in biomarkers of liver function and looked for potential gene-environmental interactions between pesticide exposure and polymorphisms of pesticide-metabolizing genes. A longitudinal study was conducted in farm-workers from Andalusia (South Spain), during two periods of the same crop season with different degree of pesticide exposure. Blood samples were taken for the measurement of serum and erythrocyte cholinesterase activities as well as for determining clinical chemistry parameters as biomarkers of liver function. Serum lipid levels were also measured as they may help to monitor the progress of toxic liver damage. A reduction in serum cholinesterase was associated with decreased levels of all clinical chemistry parameters studied except HDL-cholesterol. Conversely, a decreased erythrocyte cholinesterase (indicating long-term pesticide exposure) was associated with increased levels of aspartate aminotransferase and alkaline phosphatase and increased levels of triglycerides, total cholesterol and LDL-cholesterol, but reduced levels of HDL-cholesterol. Changes in liver biomarkers were particularly associated with the PON155M/192R haplotype. The obtained results therefore support the hypothesis that pesticide exposure results in subtle biochemical liver toxicity and highlight the role of genetic polymorphisms in pesticide-metabolizing enzymes as biomarkers of susceptibility for developing adverse health effects.

Toxic effects of pesticide mixtures at a molecular level: their relevance to human health.

Pesticides almost always occur in mixtures with other ones. The toxicological effects of low-dose pesticide mixtures on the human health are largely unknown, although there are growing concerns about their safety. The combined toxicological effects of two or more components of a pesticide mixture can take one of three forms: independent, dose addition or interaction. Not all mixtures of pesticides with similar chemical structures produce additive effects; thus, if they act on multiple sites their mixtures may produce different toxic effects. The additive approach also fails when evaluating mixtures that involve a secondary chemical that changes the toxicokinetics of the pesticide as a result of its increased activation or decreased detoxification, which is followed by an enhanced or reduced toxicity, respectively. This review addresses a number of toxicological interactions of pesticide mixtures at a molecular level. Examples of such interactions include the postulated mechanisms for the potentiation of pyrethroid, carbaryl and triazine herbicides toxicity by organophosphates; how the toxicity of some organophosphates can be potentiated by other organophosphates or by previous exposure to organochlorines; the synergism between pyrethroid and carbamate compounds and the antagonism between triazine herbicides and prochloraz. Particular interactions are also addressed, such as those of pesticides acting as endocrine disruptors, the cumulative toxicity of organophosphates and organochlorines resulting in estrogenic effects and the promotion of organophosphate-induced delayed polyneuropathy.

Análisis de la morfología del raquis torácico y lumbar en mujeres trabajadoras de una cooperativa hortofrutícola / men Analysis of the thoracic and lumbar morphology in woworkers from a fruit and vegetable company

El objetivo del presente estudio fue analizar la disposición angular del raquis torácico y lumbar en bipedestación y sedentación relajada en mujeres trabajadoras de una empresa hortofrutícola. Un total de 50 mujeres (media de edad: 43,62+/-8,43 años) fueron evaluadas mediante un spinal mouse en bipedestación y en sedentación relajada. Los valores angulares medios para el raquis torácico y lumbar fueron de 32,74+/-8,76 y -21,66+/-19,12 en bipedestación y de 36,32+/-10,55 y -1,08+/-18,14, en sedentación. En bipedestación, un elevado porcentaje de casos (86 por ciento y 68,3 por ciento) presentaban una cifosis torácica y lordosis lumbar dentro de los valores de normalidad. En sedentación, el 74 por ciento presentaban hipercifosis torácica y el 20 por ciento una inversión lumbar. En conclusión, aunque en bipedestación la mayoría de las mujeres presentaban una morfología del raquis dentro de los valores de normalidad, en sedentación se observó un elevado porcentaje de casos con hipercifosis torácica y el raquis lumbar en inversión. Debido a las consecuencias negativas que se asocian a dichas desalineaciones raquídeas, es recomendable aplicar programas de mejora de la actitud postural en estas trabajadoras, preferentemente en su contexto laboral.

The aim of this study was to analyze the sagittal spinal morphology of thoracic and lumbar spine in standing and sitting in women workers from a cooperative in the production, handling and marketing business of vegetable and fruit products. A total of 50 women (mean age: 43.62+/-8.43 years old) were evaluated. The spinal mouse system was used to mesasure the sagittal thoracic and lumbar curvatures in standing and relaxed sitting. The values for thoracic and lumbar curvatures were 32.74+/-8.76 and -21.66+/-19.12 in standing and 36.32+/-10.55 and -1.08+/-18.14 in sitting. A high frequency (86.0 percent and 68.3 percent) of normal thoracic kyphosis and lumbar lordosis were found in standing posture. While sitting the 74.0 percent and 20.0 percent presented thoracic hyperkyphosis and lumbar kyphosis. In conclusion, a high percentaje of women workers presented normality values in standing posture, although a high percentage of women were found with thoracic hyperkyphosis and lumbar flexed while sitting relaxed. It is recommended that these women carry out a program to improve their actitudinal postures in their work place.

Association between environmental exposure to pesticides and neurodegenerative diseases.

Preliminary studies have shown associations between chronic pesticide exposure in occupational settings and neurological disorders. However, data on the effects of long-term non-occupational exposures are too sparse to allow any conclusions. This study examines the influence of environmental pesticide exposure on a number of neuropsychiatric conditions and discusses their underlying pathologic mechanisms. An ecological study was conducted using averaged prevalence rates of Alzheimer's disease, Parkinson's disease, multiple sclerosis, cerebral degeneration, polyneuropathies, affective psychosis and suicide attempts in selected Andalusian health districts categorized into areas of high and low environmental pesticide exposure based on the number of hectares devoted to intensive agriculture and pesticide sales per capita. A total of 17,429 cases were collected from computerized hospital records (minimum dataset) between 1998 and 2005. Prevalence rates and the risk of having Alzheimer's disease, Parkinson's disease, multiple sclerosis and suicide were significantly higher in districts with greater pesticide use as compared to those with lower pesticide use. The multivariate analyses showed that the population living in areas with high pesticide use had an increased risk for Alzheimer's disease and suicide attempts and that males living in these areas had increased risks for polyneuropathies, affective disorders and suicide attempts. In conclusion, this study supports and extends previous findings and provides an indication that environmental exposure to pesticides may affect the human health by increasing the incidence of certain neurological disorders at the level of the general population.

Pesticides and asthma.

PURPOSE OF REVIEW: Several clinical and epidemiological studies have reported an association between exposure to pesticides, bronchial hyper-reactivity and asthma symptoms. This article reviews the mechanistic evidence lending support to the concept that either acute or chronic low-level inhalation of pesticides may trigger asthma attacks, exacerbate asthma or increase the risk of developing asthma. RECENT FINDINGS: Pesticide aerosols or gases, like other respiratory irritants, can lead to asthma through interaction with functional irritant receptors in the airway and promoting neurogenic inflammation. Cross-talk between airway nerves and inflammatory cells helps to maintain chronic inflammation that eventually damages the bronchial epithelium. Certain organophosphorus insecticides cause airway hyper-reactivity via a common mechanism of disrupting negative feedback control of cholinergic regulation in the lungs. These pesticides may interact synergistically with allergen sensitization rendering individuals more susceptible for developing asthma. SUMMARY: Many pesticides are sensitizers or irritants capable of directly damaging the bronchial mucosa, thus making the airway very sensitive to allergens or other stimuli. However, most pesticides are weakly immunogenic so that their potential to sensitize airways in exposed populations is limited. Pesticides may increase the risk of developing asthma, exacerbate a previous asthmatic condition or even trigger asthma attacks by increasing bronchial hyper-responsiveness.