324,474 research outputs found
Biological Monitoring for Pesticide Risk Assessment in Farmers and Rural Population with a Tiered Protocol
OBJECTIVES:
The assessment of exposure and of exposure-related risk for pesticides is a burdensome and expensive task. Since farmers are often exposed to many active substances, several times per year, at different working and environmental conditions, and their families, including children pregnant and breastfeeding women, the elderly, share the same environment, biological monitoring is the most promising technique for this purpose. However, there is still a difficulty to use the actual results of biological monitoring to assess individual risk, mainly due to the lack of suitable exposure limits.
METHODS:
To overcome this knowledge gap, the ICRH is currently establishing provisional Equivalent Biological Exposure Limits (EBELs) for priority pesticides. This multi-tiered approach exploits the extensive, although scattered information available in the scientific literature, in the authorization documents available from regulatory bodies, and the analysis of results from field studies.
RESULTS:
The established theoretical and computational basis and examples of the employed approach will be presented. In particular, it is possible to discriminate occupational exposure from agricultural tasks, including re-entry into treated fields, repair of agricultural equipment, from that of everyday life, from drinking water and from food. As proof-of-principle, the proposal of provisional EBELs for some priority pesticides, and an application to different agricultural tasks performed by Italian wine growers will be demonstrated.
CONCLUSIONS:
The establishment of a robust protocol for the determination of EBELs will allow individual risk assessment for farmers, for their families and for the general population of rural areas with moderate effort and cost.
REFERENCES:
Rubino FM, Mandic-Rajcevic S, Colosio C. et al. Toxicol Lett. 2012 Apr 25;210(2):189-97.
Colosio C, Rubino FM, Alegakis A, Mandic-Rajcevic S, et al. Toxicol Lett. 2012 Aug 13;213(1):49-56
A prototype algorithm to calculate Health-based occupational exposure limits for a safe use3 of pesticides
Due to the limitations of the environmental monitoring in agriculture, and the potential advantages of biological monitoring, the identification of biological exposure limits for pesticide bio-monitoring is a timely and needed activity. We are therefore establishing algorithms to calculate some limits that take advantage of the availability, for most of the active ingredients of pesticides marketed in the EU, of the health-based limit “Acceptable Operator Exposure Level (AOEL)” and of an extensive toxicological information that often includes dermal absorption coefficients. The AOEL is the systemic dose of a pesticide that a worker can absorb during each working day without any long-term consequences for his health. However, the AOEL is expressed as a systemic dose, which is not directly comparable with measurable indicators. Therefore, the AOEL is mostly used in the pre-marketing risk assessment, when which the internal dose is calculated, rather than measured. This weakness hampers its preventive value for the routine monitoring of agricultural workers.
In order to calculate provisional biological limits of pesticides from their AOELs, we collected, in real life scenarios of Northern Italy, pesticide metabolite measurements in 24-hour urine, along with data on skin contamination levels, measured through skin pads. A plot of urinary excretion of pesticide metabolite vs. personal exposure referred to the AOEL limit (individual risk assessment) allows to calculate a tentative value for an Equivalent Biological Exposure Limit (EBEL). With this approach, we obtained two proof-of-principle results on a herbicide (propanil, EBEL=1 mg 3,4-DCA/L 24-h urine) and on a fungicide (mancozeb, EBEL=117 microg ETU/L 24-h urine).
The same approach allows foreseeing a provisional corresponding value for other related pesticides, based on the known use rates, absorption coefficients and respective AOELs, as demonstrated by a calculation that expands the EBEL limit as ETU to other dithiocarbamates.
This pilot study demonstrates that this method can be adopted to calculate “Health-Based Biological Exposure Limits” for biological monitoring of pesticide workers, and, in perspective, to establish EBELs in the pre-marketing phase to become part of the information made available when a new active ingredient is marketed
EXPLORING NOVEL APPROACHES TO PESTICIDE EXPOSURE AND RISK ASSESSMENT
Introduction. Agrochemicals, short from agricultural chemicals, is a term used for various chemical products which are commonly used in agriculture. The most famous representative example of agrochemicals are pesticides, but it may also include fertilizers, hormones or similar chemical growth agents, as well as raw animal manure. Even as an active substance is authorized in European Union, and products containing this active substance are authorized and marketed, there is still a need for risk assessment to communicate and to manage risk with regard to the different risk groups, workers and the general population as a whole.
Overall Goal. The goal of this effort is the creation of Exposure and Risk Profiles, as a reliable, scientifically based way to forecast pesticide exposure and workers’ risk in typical scenarios from a minimum set of available information, aimed at performing a preliminary risk assessment even without the need of “in field” measurements.
Methodology. To reach our goal we have conducted a wide published literature search to define the process of pesticide application and the most common exposure determinants. Then we conducted two real-life field studies on exposure to pesticide in different use scenarios in the vineyards of the Region of Lombardy (one study in the framework of the ACROPOLIS project of the European Union, and another financed by INAIL). We collected field information in the form of a structured questionnaire, with a goal to record the variables previously identified as important modifiers of pesticide exposure. Also we collected exposure measurements, using two methodologies: skin pads and whole-body method, following in principle the OECD guidelines. Finally, we used the results from the field to develop a method that allows for a re-use of field data in risk assessment, by creating a Risk Assessment Scheme which can be used to assess risk in the field, without doing any measurements.
Results. We report the main phases of pesticide work and variables, together with their influence, as a result of our wide literature search. Also we report the results of two field studies, first on 7 workers applying Tebuconazole on 12 work-days, and second on 28 workers applying Mancozeb on 38 work-days. Finally, we show a proposed approach to using field measurements from our study in the Region of Lombardy to perform future risk-assessment in one defined scenario of closed and filtered tractors.
Discussion and Conclusions. Our work has tackled the problem of risk assessment for pesticide exposure in agriculture, which has been unfairly neglected in the past years. Through the use of literature data, field studies and computational modelling, we have managed to analyze and summarize the characteristics of pesticide application in agriculture, explore the real-life field conditions during pesticide application in vineyards in Italy, collect the field measurements necessary to do exposure and risk assessment, and to develop a method to use the data collected to produce a Risk Assessment Scheme. The study results and the above mentioned tool represent a step forward towards rapid, simple and scientifically based risk assessment in real-life conditions of pesticide application in agriculture
From Pre-marketing Studies and Authorization Dossiers to New Prospects for Pesticide Risk Assessment in Rural Enterprises
The role of pesticides in the modern society has been strengthened by the need for higher yield in food production and the ongoing battle against vector borne diseases in public health. Nevertheless, the toxicity of these chemicals is not fully specific to target organisms, thus posing a potential health threat to humans. In this frame, risk assessment and management are fundamental. In the occupational settings, variability of meteorological conditions, use of different concentrations of variable mixtures, and significant variations in the application times and modalities make this task very complicated, making necessary proposing novel approaches for conducting “in field” preventive activities. The amount of information collected during the process of authorization of a new active ingredient is unique, with a size similar of the one available for human drugs. Therefore, a possible way forward for risk assessment is represented by a better exploitation in the post-marketing phase of the data used for the registration process, combined with the data collected in real-life field studies usable for refining and validate the risk hypothesis generated through modelling. In particular, parameters such as Acceptable Operator Exposure Level (AOEL), acute reference dose (ArD) as well data regarding skin absorption, metabolism and relevant metabolites in animals can find use in the conduction of risk assessment activities in agricultural enterprises, through the creation of new tools for exposure and risk assessment. Such tool are usable even without conducting complicated and expensive measures, and therefore are adequate for the needs of small and medium sized agricultural enterprises
The Importance of Open Data in Toxicological Research and Publishing
Every year thousands of toxicological studies are performed around the World. These studies are most commonly funded by Governmental, Non-Governmental agencies, Universities, Faculties, and in the last 50 years even more so by funds provided by research funding schemes such as the Horizon 2020 and the Framework Programmes in the European Union, or the National Institutes of Health in the United States. As part of these studies, thousands of experiments and field studies are done, collecting millions of tables of data ranging from genotypes and cell-culture reactions to chemical agents, to epidemiological data on populations from different towns and countries. In addition, governmental agencies and private companies measure a vast amount of parameters regarding the environment. Recently, a very specific risk has come to attention of research funders: the results of a specific research project are published in a peer review journal, thus satisfying the basic requirements of the project call, and the raw data which was collected remains buried (or lost) in the hard-disk of participating researchers. To resolve this situation, many institutions have adopted the „Open Data“ policy, which should allow the data collected by these institutions or projects funded by them to be freely available to use and re-use by others. This philosophy was also adopted by many journals which now allow the authors of published articles to store even the raw data in their online repositories. This new trend, which might soon become a rule in the scientific publishing world, considering there are journals specifically designed to store datasets and study protocols, increases the use of already collected data, facilitates data re-use and new discoveries, but also helps authors achieve a higher impact and recognition than by just publishing their work
Establishing health-based biological exposure limits for pesticides : A proof of principle study using mancozeb
Pesticides represent an economical, labor-saving, and efficient tool for pest management, but their intrinsic toxic properties may endanger workers and the general population. Risk assessment is necessary, and biological monitoring represents a potentially valuable tool. Several international agencies propose biological exposure indices (BEI), especially for substances which are commonly absorbed through the skin. Biological monitoring for pesticide exposure and risk assessment seems a natural choice, but biological exposure limits (BEL) for pesticides are lacking. This study aims at establishing equivalent biological exposure limits (EBEL) for pesticides using real-life field data and the Acceptable Operator Exposure Level (AOEL) of mancozeb as the reference. This study included a group of 16 vineyard pesticide applicators from Northern Italy, a subgroup of a more extensive study of 28 applicators. Their exposure was estimated using “patch” and “hand-wash” methodologies, together with biological monitoring of free ethylene-bis-thiourea (ETU) excretion in 24-h pre- and post-exposure urine samples. Modeling was done using univariate linear regression with ETU excretion as the dependent variable and the estimated absorbed dose as the independent variable. The median skin deposition of mancozeb in our study population was 125 μg, leading to a median absorbed dose of 0.9 μg/kg. The median post-exposure ETU excretion was 3.7 μg. The modeled EBEL for mancozeb was 148 μg of free ETU or 697 μg of total ETU, accounting for around 75% of the maximum theoretical excretion based on a mass balance model. Although preliminary and based on a small population of low-exposed workers, our results demonstrate a procedure to develop strongly needed biological exposure limits for pesticides
Duration of Skin Exposure: a Neglected Variable in Absorbed Dose Assessment
The use of pesticides has become unavoidable in agriculture as it ensures the massive production of food crops and their global trade, as well as solves public health problems by eradicating vectors of human diseases such as malaria. Besides risk assessment done in the pre-marketing phase, field studies allow for the re-evaluation of exposure and risk in real-life working conditions, opening new possibilities for risk assessment and modeling. In agriculture, special attention must be given to the skin as the main route of exposure, but the fixed fractional approach to dermal absorption might not represent the perfect solution to absorbed dose assessment. Here we present a practical method for integrating the information on the duration of exposure into the absorbed dose assessment, using a group of mancozeb applicators as a case study. Assumption of an 8-hour exposure resulted in a gross overestimation of absorbed dose from hands’ exposure. Absorbed dose from body exposure was overestimated in those workers working less than 8 hours, but somewhat underestimated in those working more than 8 hours, which is common in agriculture. In total, an 80% reduction of the absorbed dose estimate resulted from the introduction of the duration of exposure as a factor. This reduction did not influence risk assessment significantly for substances with low toxicity such as mancozeb, but implications for modeling might be much more important
Emerging health effects from pesticide exposure in Europe and in developing countries
Human exposure to agrochemicals brings about a significant portion of the global burden of disease. Although levels of exposure have been significantly reduced in Europe, they still remain high in the developing world, bringing about specific emerging health risks. The estimated number of acute pesticide poisoning is 250,000-500,000, with 3,000 to 30,000 deaths each year, mainly in developing countries. In these countries the highest rates of intentional poisonings also occur, with a total number of more than 870,000, most by pesticide ingestion. Acute pesticide poisoning can affect neurobehavioral functioning, perhaps through brain anoxia, but published literature suggests that also prolonged or repeated exposures can affect behavior. Neurobehavioral impairment in previously acutely poisoned subjects is documented, but neurobehavioral effects in chronically exposed subjects are still controversial, and different opinions are present. Existing evidence suggests that the risk is higher for the higher levels of exposure, such as those experienced in the developing world with, in some cases, mental health impairment, increased risk of depression and even suicide. Another emerging toxic effects currently under study is ‘endocrine disruption’ (ED), able to influence reproductive capability, thyroid function, risk of diabetes and to increase the risk for some specific tumors of hormone-controlled organs. As for cancer as a whole, despite the large number of studies available on the topic it can be concluded that there is not enough evidence that chronic pesticide exposure is responsible for cancer, apart from well known and nowadays forbidden carcinogenic compounds
Environmental Lead Exposure in Children: a Problem of Developing Countries?
Environmental exposure to lead, although not an important cause of mortality, represents one of the main causes of morbidity among children and adolescents. In general, rural communities are expected to have significantly lower blood lead levels (BLLs) than urban communities. However, this is not the case in populations living in the vicinity of lead mines and smelting facilities, where higher BLLs may occur, particularly among young children. Around 50% of Global lead production can be traced back to car battery recycling.
The aim of this study was to quantify blood lead levels (BLLs) of children living near a car battery smelting facility in Serbia, compare the levels with developed and developing countries’ standards, and identify the main determinants of lead exposure in this population. BLLs were quantified in 75 children from Zajača, a village where a car battery smelting factory is located, and 52 children from Paskovac, village 5 kilometers away from Zajača. The median BLL for both groups were 12 μg/dl, 7.60 μg/dl in children from Paskovac, and 17.5 μg/dl in children from Zajača. Even 87% of children from Zajača had the BLL above 10 μg/dl, which is comparable to urban schoolchildren in South Africa and Bangladesh. Although a European country, a candidate country for the European Union, BLLs of Serbian children were comparable to that of children living in developing countries and higher than those expected in children living near lead smelting facilities in developed countries
Improving the Quality of Toxicological Research Findings Using Modern Principles of Reproducible Research
Reproducibility represents the foundation of scientific work and publications, and the materials and methods section in each published article should allow any researcher to repeat the experiment in question and get the same or similar results. Nevertheless, in most scientific papers the data analysis procedure is rarely described well, and it often contains just the basic information on statistical procedures performed. We present all of the basic steps in doing reproducible data analysis, with all the advantages and disadvantages over the non-reproducible methods, on a case study of pesticide exposure and risk assessment. Data is imported from multiple sources (text, excel, access database), and basic description of acquired data, visual and numerical comparison between groups, and modelling of data acquired in real-life studies of pesticide exposure in agriculture are presented. The final products of the data analysis process, tables and figures which are ready for the revision process, are compiled using the R Language and Environment for Statistical Computing and additional packages. Considering the more strict requirements for funding and the increased competition, as well as the slow (but certain) move towards open access, open review and data exchange, doing data analysis the reproducible way will become inevitable in toxicology, as well as other scientific fields. Popularization and training on using free statistical and reproducible research tools should be a priority for young researchers entering this field, as this will result in the improvement of the quality of toxicological research, leading to easier publishing
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