Health effects of pesticides. An impression of recent scientific literature August 2010. Acute and chronic pesticides exposure could cause several health problems and serious diseases. Many scientific studies proved a link between pesticides exposure and cancer, leukemia, disruption of the endocrine, immune or neural system. All of us are exposed indirectly to pesticides and other agrochemicals via food, water, gardening and household use or spray drift. Farmers, farm workers and their families are in direct contact with the chemicals, sometimes daily. Young children can be more exposed to pesticides because they play on the ground and their hands and mouth are in contact with potential contaminated surface. Developing brain and neural system of children and fetus are more susceptible to damage than adults. Exposure of pregnant women may contribute to an increased risk of childhood cancer and neurodevelopment disorders. Long-term lowdose exposure is also suspected to increase the risk for Parkinson’s and Alzheimer’s disease. Some pesticides could also act as endocrine disruptors and promote hormonal disorders, affect reproduction or contribute to a spontaneous abortion and possibly to prolong time-to-pregnancy. Evidence on exposure of farmers to pesticides Farmers and people who works in agriculture are more likely to be expose to pesticides and other agricultural agents. Below, evidences about pesticides exposure among farmers is presented. The Agricultural Health Study http://www.aghealth.nci.nih.gov/index.html This large long-term study of farm families and commercial pesticides applicators has been conducted since 1993. It includes almost 90,000 participants from most of the farms in both Iowa and North Carolina. The study is focused on a better understanding of how agricultural chemical exposure can affect risk of cancer and other diseases and what factors may work to promote good health. The results confirmed that farm homes had higher amounts of pesticide residues in air, dust and hard surface samples as compared to non-farm homes. Chlorpyrifos, Glyphosate and 2,4-D were found most often. Traces of these pesticides were also found in children’s bedrooms and playrooms. Farmer’s children had significantly higher urinary Atrazine and Chlorpyrifos levels when their fathers applied these pesticides in comparison to “not affected” children. Other findings show on higher rates of prostate cancer between farmers, increased risk of Parkinson’s disease and more often occurrence of lung diseases or depression by lower levels of pesticide exposure. A detailed description and findings of this study so far are available on the study website. http://www.aghealth.nci.nih.gov/index.html. A serious risk of pesticides exposure exists also in greenhouse agriculture. Organochlorine pesticides (DDT, aldrin, endosulfan, lindane and their metabolites) were determined in adipose tissues of women from agricultural areas in Southern Spain, who were employed in greenhouses (Cerrillo et al., 2006). Abstract: http://www.ncbi.nlm.nih.gov/pubmed/16153679 Full text (pdf): http://hera.ugr.es/doi/16519838.pdf 1 Pesticides metabolites are often detected in urine samples. Metabolites of organophosphates like parathion, chlorpyrifos and diazinon were found in urine from farmworker’s children in Northern Carolina. In boys, children living in rented housing, and children with mothers working part-time more metabolites were analysed (Arcury et al., 2007). Abstract and full text: http://www.ncbi.nlm.nih.gov/pmc/articles/PMC1940070/ The study with farmwarker’s children in the Salinas Valley, California detected several pesticides residues in house dust, surface wipes, socks and other clothing. Chlorpyrifos, Diazinon, Chlorthal-dimethyl, and Cis- and Trans-permethrin were detected more frequently. Several organophosphate pesticides, as well as 4,4′-DDE, atrazine, and dieldrin were also found in the food samples (Bradman et al., 2006). Abstract: http://www.nature.com/jes/journal/v17/n4/full/7500507a.html Household dust containing significant residues of various pesticides is frequently found in large amount of farmer’s homes suggesting that low-level exposure to such chemicals occurs for farmers children and families (Simcox et al., 1995; Harnly et al., 2009). Abstract and full text: 1. http://www.ncbi.nlm.nih.gov/pmc/articles/PMC1519258/ 2. http://pubs.acs.org/doi/abs/10.1021/es9020958 Outdoor air exposure: Agricultural applications of organophosphates and their oxon products may also have substantial volatization and off-field movement and thus be a probable source of exposures of public health concern (Harnly et al., 2005). Abstract anf full text: http://www.ncbi.nlm.nih.gov/pmc/articles/PMC1280399/ Inner cities exposure, home use of pesticides and biocides Also children in inner cities are at high risk of exposure to pesticides that are used extensively in urban schools, homes, and day-care centers for control of roaches, rats, and other vermin. The exposure is moreover enhanced due to longer persistence of pesticides in the urban indoor environment, especially semi volatile pesticides such as Chlorpyrifos that could be absorbed to toys, carpets or soft furniture. Among pesticides, insecticide Chlorpyrifos, certain Pyrethroids and Carbamathes are the most heavily applied in cities and homes and also most often detected (Landrigan et al., 1999). Abstract and full text: http://www.ncbi.nlm.nih.gov/pmc/articles/PMC1566233/ Prenatal exposure to Chlorpyrifos can damages children’s neurodevelopment and have negative impacts on cognition, motor skills and possibly behavior that might be lifelong. Although residential use of Chorpyrifos was banned in the US, concern persists due to possible exposure by agricultural use (Rauh et al., 2006). Abstract and full text: http://pediatrics.aappublications.org/cgi/content/abstract/118/6/e1845 Results of a large case study from Europe (England) proved that domestic use of biocides and insect repellents during the first trimester of pregnancy increase a risk of hypospadias (birth defect of urethra in the male) at children (Dugas et al., 2010). Abstract: http://oem.bmj.com/content/67/3/196.abstract 2 A review article showed positive associations between self-reported home insecticide use and childhood leukemia in North and South America and Europe over the past two decades (Metayer et al., 2008). Abstract and full text: http://rpd.oxfordjournals.org/content/early/2008/10/21/rpd.ncn266.abstract Dietary exposure. Food is an important source of pesticides. This exposure poses a greater health risk to children as compared to adults, because children consume more food on a per-weight basis than adults, they also may be more vulnerable to the effects of toxicants because they are still developing. The rising occurrence of multiple residues in European food is very worrying. Consumers are exposed to dozens residues every day. http://www.efsa.europa.eu/en/scdocs/doc/1646.pdf A study focused on exposure to OP pesticides among children showed that dietary intake is a major source of OP pesticide exposure. When children switched to organic diet a level of urine metabolites significantly decreased (Lu et al., 2006). Abstract and full text: http://www.ncbi.nlm.nih.gov/pmc/articles/PMC1367841/ Pesticide exposure and specific health effects. 1. Neurotoxicity, developmental and brain disorders Many pesticides compounds target the nervous system of insect pests. Because of the similarity in brain biochemistry they may also be neurotoxic to human. The review article below presents an overview of the evidence on neurotoxicity of pesticides in current use in Europe, such as organophosphates, carbamates, pyrethroids, ethylenebisdithiocarbamates, and chlorophenoxy herbicides. Experimental, clinical and epidemiological evidence suggests that neurotoxic pesticides can also cause developmental neurotoxicity, and that the effects are more severe and lasting, and that they occur at much lower exposure levels. Despite some substances have now been banned or restricted currently used substances with similar mechanisms of toxicity should be regarded to share the same toxic potentials. (Bjorling-Poulsen et al., 2008). Abstract and full text: http://www.ehjournal.net/content/7/1/50 Results of the study with pregnant women from agricultural area in Salinas Valley in California provide evidence of negative association of child mental development and maternal DDT and DDE serum levels, as well as prenatal and child organophosphate urinary metabolite levels (Eskenazi et al., 19991; Eskenazi et al., 20082). Abstract and full text: 1 http://www.ncbi.nlm.nih.gov/pmc/articles/PMC1566222/ http://onlinelibrary.wiley.com/doi/10.1111/j.17427843.2007.00171.x/abstract 2 Parental occupation and residential activities are sources of children exposure to carcinogens, neurotoxins, and microorganisms that could increase risk of brain cancer. According to this study, exposure to herbicides from residential use and paternal exposure to pesticides during the 2 years before birth elevated the risk of brain cancer, in particular astrocytoma (Shim et al., 2009). Abstract and full text: http://www.medscape.com/viewarticle/706850 3 2. Risk for Alzheimer’s and Parkinson’s Disease According to an observational study published in Neurology (Hayden et al., 2010) repeated exposure to organophosfhate and organochlorine pesticides, such as occurs with occupational use, is associated with an increase in the risk for incident dementia and Alzheimer's disease in late life. In this study residents of the agricultural community in Utah, who were aged 65 years, were examined. Abstract: http://www.neurology.org/cgi/content/abstract/74/19/1524 Researchers also link chronic exposure of low dose of pesticides and increase a risk of Parkinson’s disease (PD) (Ascherio et al., 2006)1. Moreover, there might exist a risk of PD and consuming of well water presumably contaminated by agricultural pesticides as proved another study in 2006 (Gatto et al., 2009) 2. Authors studied a large agricultural population in California and data about pesticides use in that area over 26 years. They found out that high levels of possible well-water contamination with water-soluble pesticides and organophosphate pesticides (from total 26, methomyl, chlorpyrifos and propargite were most significant) resulted in approximately 70–90% increases in relative risk of PD. Although the pesticides were evaluated individually, they presumed that rather exposure to a number of these types of pesticides in water might increase PD risk. Abstract and full text 1 http://onlinelibrary.wiley.com/doi/10.1002/ana.20904/abstract Abstract and full text 2 http://ehp03.niehs.nih.gov/article/fetchArticle.action?articleURI=info:doi/10.1289/e hp.0900852 3. Attention-Deficit/Hyperactivity Disorder (ADHD) and Urinary Metabolites of Organophosphate Pesticides Organophospates are among the most widely used pesticides. Exposure to OP has been associated with adverse effects on neurodevelopment, such as behavioral problems, lower cognitive function, poorer short-term memory and motor skills at children. These problems may occur at both, prenatal and postnatal OP exposure. The study published in Pediatrics in 2010 (Bouchard et al., 2010) adds findings that children with higher urinary levels of organophosphate metabolites were more likely to meet the diagnostic criteria for ADHD. In this study concentration of OP metabolites were measured at more than thousand children of age from 8 to 15 years in US population. Their results also support the hypothesis that current levels of OP exposure might contribute to the childhood burden of ADHD. Authors also showed on that concentration of OP metabolites among children have not decrease from 2000. Abstract and full text: http://pediatrics.aappublications.org/cgi/content/abstract/peds.2009-3058v1 the recommended herbicide agricultural dilutions (from 104 ppm) and could be expected around residual levels, especially in food and feed derived from Roundup formulation-treated crops. (Benachour et al., 2008) Abstract and full text: http://pubs.acs.org/doi/abs/10.1021/tx800218n 4. Endocrine disruption and reproductive disorder Many pesticides have been shown to affect the animal and human endocrine system. Some of them are strongly resistant to biodegradation and accumulate in the food chain human. These chemicals can bind to hormone receptors and cause reproductive disorder. They are also regarded as a risk 4 factor for hormone-dependent cancer. A large quantities of endocrine-disrupting chemicals has been released into the environment since World War II and have harmfully affected wildlife population as well as human (Colborn et al., 1999). Abstract and full text: http://ehp.niehs.nih.gov/realfiles/members/1993/101-5/colborn- full.html Intensive use (legally or illegally) of endocrine disrupting pesticides (such as DDT toxaphene, endosulfan, 1-hydroxychlordene, dicofol, heptachlor, dieldrin, chlordecone, and [beta]-HCH, triazine, tributhyltin) remains in many countries. The incidence of hormone-related organ cancers, or hormonal cancers, is elevated among farmers, who are expose to pesticides over longer periods (Buranatrevedh et al., 2001) . Abstract: http://www.ncbi.nlm.nih.gov/pubmed/11605324 A study from Pakistan also point out the increased incidence of cancer (breast, ovary, prostate, testis and thyroid cancer) among farmers and allied people who have been using banned chemical (Sohail et al., 2004). Full text (pdf): http://www.tumorbio.sote.hu/Elte-kb-2009/8-ea/ED-pest-UA-paper.pdf A study among Dutch greenhouse male and female farmers got some evidence that pesticide exposure affects human reproduction leading to spontaneous abortion and possibly to prolonged time-to-pregnancy (Bretveld et al., 2008)4. Abstract : http://www.sciencedirect.com/science/article/B6TC0-4PMT2V3- 1/2/88e9b4275776183cb7769c9043fbc7c6 Vinclozolin, a common fungicide used to protect grapes for the wine industry, is known as hormone disruptors. Recent scientific findings observed that embryonic exposure to vinclozolin in rats developed a number of disease states or tissue abnormalities (including prostate disease, kidney disease, immune system abnormalities, testis abnormalities, and tumor development) that last for four generation (Anway et al., 2006). Abstract and full text: http://endo.endojournals.org/cgi/content/abstract/147/12/5515 According to the recent study, male reproductive disorders, such as testicular cancer and impaired semen quality, can be link with perinatal exposure to persistent halogenated compounds and phtalates. The prevalence of reproductive disorder can be , however, results of overall life style and simultaneous exposure to chemicals with disrupting properties, especially during foetal life and infancy (Main et al., 2010). Abstract : http://www.bprcem.com/article/S1521-690X(09)00140-7/abstract Thyroid disfunction Authors show on increasing evidence that environmental exposures to pesticides should also be considered potential risk factors for thyroid disease. They examined thyroid dysfunction (hyperthyroidism and hypothyroidism) in female spouses of pesticide applicators in Iowa and Nothern Carolina According to their results prevalence of self reported clinical thyroid disease was 12.5%, higher than in the general population. Hypothyroidism was the most common abnormality and was associated with the use of fungicides, benomyl, maneb/ mancozeb, and herbicide paraquat in addition to the class of organochlorines that includes aldrin, DDT, heptachlor, lindane, and chlordane (Goldner et al., 2010). Abstract: http://aje.oxfordjournals.org/cgi/content/abstract/171/4/455 5 In addition, there exist also evidences that thyroid disorders may be cause by nitrate fertilizers. Nitrates have been shown to cause thyroid tumors in animal studies. According to the new study of older women in Iowa, long-term consumption of food and water with higher concentration of nitrate may increase a risk of thyroid disease and thyroid cancer in people. The women in this study who were hardest hit by thyroid disorders tended to be better-educated, physically active nonsmokers - a group that is more likely to eat vegetables (Ward et al., 2010). Abstract and full text: http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2879161/ Review articles that provide current literature overview and evidence of pesticides health effects. Turner et al., 2009: A systematic review of observational epidemiological studies (form 1950 to 2009) by proved evidence that exposure during pregnancy to unspecified residential pesticides, insecticides and herbicides were positively associated with childhood leukemia. Abstract and full text: http://ehp03.niehs.nih.gov/article/info%3Adoi%2F10.1289%2Fehp.0900966 (Julvez et al., 2009): This review covers the background information and the modest epidemiological evidence on occupational exposures of female workers to industrial chemicals and pesticides (organochlorinated, organophosphates) and the consequences in regard to the child’s neurodevelopment. The overall experimental and epidemiological evidence suggests that the substantial vulnerability of the developing nervous system to low concentrations of neurotoxic chemicals should lead to a strengthened emphasis on protection of pregnant workers and women in general against substances that may cause harm to the fetus. Abstract: http://www.ncbi.nlm.nih.gov/pubmed/19834254 References: Anway, M.D., Leathers, C., Skinner, M.K. (2006): Endocrine Disruptor Vinclozolin Induced Epigenetic Transgenerational Adult-Onset Disease. Endocrinology 147(12), pp 5515-5523. 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