Antonio F. Hernández

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.

Determination of toxic elements (mercury, cadmium, lead, tin and arsenic) in fish and shellfish samples. Risk assessment for the consumers

Although fish intake has potential health benefits, the presence of metal contamination in seafood has raised public health concerns. In this study, levels of mercury, cadmium, lead, tin and arsenic have been determined in fresh, canned and frozen fish and shellfish products and compared with the maximum levels currently in force. In a further step, potential human health risks for the consumers were assessed. A total of 485 samples of the 43 most frequently consumed fish and shellfish species in Andalusia (Southern Spain) were analyzed for their toxic elements content. High mercury concentrations were found in some predatory species (blue shark, cat shark, swordfish and tuna), although they were below the regulatory maximum levels. In the case of cadmium, bivalve mollusks such as canned clams and mussels presented higher concentrations than fish, but almost none of the samples analyzed exceeded the maximum levels. Lead concentrations were almost negligible with the exception of frozen common sole, which showed median levels above the legal limit. Tin levels in canned products were far below the maximum regulatory limit, indicating that no significant tin was transferred from the can. Arsenic concentrations were higher in crustaceans such as fresh and frozen shrimps. The risk assessment performed indicated that fish and shellfish products were safe for the average consumer, although a potential risk cannot be dismissed for regular or excessive consumers of particular fish species, such as tuna, swordfish, blue shark and cat shark (for mercury) and common sole (for lead).

Biomonitorization of cadmium, chromium, manganese, nickel and lead in whole blood, urine, axillary hair and saliva in an occupationally exposed population

Heavy metal contamination from occupational origin is a cause for concern because of its potential accumulation in the environment and in living organisms leading to long term toxic effects. This study was aimed to assess Cd, Cr, Mn, Ni and Pb levels in whole blood, urine, axillary hair and saliva from 178 individuals with occupational exposure to heavy metals. Levels of metal compounds were determined by atomic absorption spectrometry. We collected information on occupation, lifestyle habits and food intake by questionnaire. Multiple linear regression analyses for metal ion concentration in whole blood, urine, axillary hair and saliva were adjusted for age, gender, smoking and alcohol consumption, lifetime workplace exposure, residence area and food habits. Overall, blood and urine median concentrations found for the five metals analyzed do not exceed biological exposure indexes, so that they are very similar to a non-occupationally exposed population. Toxicokinetic differences may account for the lack of correlations found for metal levels in hair and saliva with those in blood or urine. For those heavy metals showing higher median levels in blood with respect to hair (Cd, Mn and Pb) indicating lesser hair incorporation from blood, the lifetime working experience was inversely correlated with their hair levels. The longer the lifetime working experience in industrial environments, the higher the Mn and Ni concentration in saliva. Axillary hair and saliva may be used as additional and/or alternative samples to blood or urine for biomonitoring hair Mn, and saliva Ni in subjects with occupational exposure.

Validation of a method to quantify chromium, cadmium, manganese, nickel and lead in human whole blood, urine, saliva and hair samples by electrothermal atomic absorption spectrometry.

For biological monitoring of heavy metal exposure in occupational toxicology, usually whole blood and urine samples are the most widely used and accepted matrix to assess internal xenobiotic exposure. Hair samples and saliva are also of interest in occupational and environmental health surveys but procedures for the determination of metals in saliva and hair are very scarce and to our knowledge there is no validation of a method to quantify Cr, Cd, Mn, Ni and Pb in four different human biological materials (whole blood, urine, saliva and axilary hair) by electrothermal atomization atomic absorption spectrometry (ETAAS). In the present study, quantification methods for the determination of Cr, Cd, Mn, Ni and Pb in whole blood, urine, saliva and axilary hair were validated according to the EU common standards. Pyrolisis and atomization temperatures have been determined. The main parameters evaluated were: detection and quantification limits, linearity range, repeatability, reproducibility, recovery and uncertainty. Accuracy of the methods was tested with the whole blood, urine and hair certified reference materials and recoveries of the spiked samples were acceptable ranged from 96.3 to 107.8%.

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 Alzheimers disease, Parkinsons 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 Alzheimers disease, Parkinsons 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 Alzheimers 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.

Immunohistochemical evidence for the expression and induction of paraoxonase in rat liver, kidney, lung and brain tissue. implications for its physiological role

Studies on the localization of paraoxonases (PONs) are of interest because of its involvement in both the detoxication of activated organophosphorus pesticides and in the prevention of peroxidative damage to phospholipids and cholesteryl-esters in LDL and HDL particles and cell membranes during the atherogenic process. In the present study, we have investigated the cellular localization of PON1 by immunohistochemistry in different rat tissues. The protein was mainly detected in the endothelial lining of every tissue studied (liver, kidney, lung and brain). Besides, it was found in hepatocytes from the centrolobular region of the liver, in the glomeruli and basal pole of the proximal convoluted tubule of the kidney, in cells from bronchiolar epithelium and type I pneumocytes of the lung, and in leptomeningeal cells, ependymal cells and ventricular side of choroid plexus cells of the brain. However, neurons and glia lacked immunostaining. After 3-methylcholanthrene induction an increase in the intensity of immunostaining was observed in the same areas, as well as an additional staining in midzonal hepatocytes. On the basis of the tissue distribution observed for PON1, it is proposed that this enzyme might have a function related to the inactivation of oxidative stress by-products (either at a cellular level or blood-vessel wall) and other environmental chemicals. At present it has not yet been established whether the paraoxonase detected in the various tissues is truly a product of the PON1 gene or could represent products of the PON2 or PON3 genes.

Increased risk of suicide with exposure to pesticides in an intensive agricultural area. A 12-year retrospective study

Several reports have suggested that exposure to agricultural pesticides (mainly chronic exposure to organophosphates) produces depression, and depression is a major risk factor for suicide. A retrospective epidemiological study of 251 suicide cases was undertaken to explore the possible relationship between the high suicide rates in an intensive agricultural area, and a specific group of population at risk, namely farmers with chronic exposure to pesticides, who are at risk to develop mood disorders (mainly depression). Our data show that the suicide rate in that area is significantly higher than the suicide rates from other geographic areas with very similar socioeconomic and demographic features. In addition, the mortality from suicide in this population (farmers) does differ significantly from that of the rest of the population.

A mechanistic overview of health associated effects of low levels of organochlorine and organophosphorous pesticides

Organochlorine and organophosphate pesticides are compounds that can be detected in human populations as a result of occupational or residential exposure. Despite their occurrence in considerably low levels in humans, their biological effects are hazardous since they interact with a plethora of enzymes, proteins, receptors and transcription factors. In this review we summarize the cell and molecular effects of organochlorine and organophosphate pesticides with respect to their toxicity, with particular emphasis on glucose and lipid metabolism, their interaction with some members of the nuclear receptor family of ligand-activated transcription factors, including the steroid and peroxisome proliferator activated receptors that changes the expression of genes involved in lipid metabolism and xenobiotic detoxification. More importantly, evidence regarding the metabolic degradation of pesticides and their accumulation in tissues is presented. Potential non-cholinergic mechanisms after long-term low-dose organophosphate exposure resulting in neurodevelopmental outcomes and neurodegeneration are also addressed. We conclude that the mechanism of pesticide-mediated toxicity is a combination of various enzyme-inhibitory, metabolic and transcriptional events acting at the cellular and molecular level.

Pesticides and asthma.

Purpose of reviewSeveral 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 findingsPesticide 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. SummaryMany 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.

Clinical and biochemical changes in greenhouse sprayers chronically exposed to pesticides

1 This study was conducted with the aim of evaluating the impact on health produced by the use of different types of pesticides in greenhouses. It is based on the need to practice and develop biological monitoring techniques to assess exposure and predict health risk in workers occupationally exposed to pesticides. 2 Two groups of greenhouse workers with either high or low exposure to a combination of pesticides was taken in Almeria, a Spanish province where cultures under plastic are very extended. 3 One hundred and five sprayers were interviewed to collect information about symptoms and signs related to past exposures. Each pesticide sprayer was exam ined by a physician, and a blood sample was drawn for plasma and red blood cell cholinesterases, complete blood count, and liver and renal function tests. 4 Exposure of workers to a combination of pesticides resulted in 37% of the workers showing toxic signs and symptoms. The main toxic effects observed were a high incidence of spontaneous abortion, depression, and certain neurologic disorders like headache, tremor and paraesthesia. 5 The major analytical change was a decrease of the mean corpuscular haemoglobin concentration in 38% of the cases. However, no significant decrease in both serum and erythrocyte cholinesterase activities was observed. 6 The sprayers were not usually aware of the potential hazards of pesticides and did not try their best to maintain personal hygiene.