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      Pesticide Exposure and Risk of Rheumatoid Arthritis among Licensed Male Pesticide Applicators in the Agricultural Health Study

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          Abstract

          Background:

          The occupation of farming has been associated with rheumatoid arthritis (RA); pesticides may account for this association, but there are few studies.

          Objectives:

          We investigated associations between RA and use of pesticides in the Agricultural Health Study.

          Methods:

          The study sample was drawn from male pesticide applicators enrolled in 1993–1997 who provided questionnaire data at baseline and at least once during follow-up (over a median 18 y; interquartile range 16–19). Incident RA cases ( n = 220 ), confirmed by physicians or by self-reported use of disease-modifying antirheumatic drugs, were compared with noncases ( n = 26,134 ) who did not report RA. Odds ratios (ORs) and 95% confidence intervals (CIs) were estimated using logistic regression, adjusting for enrollment age, state, smoking pack-years, and education. We evaluated the association of RA with the use of 46 pesticides and across 4 levels (never use and tertiles) of lifetime days of use for 16 pesticides with OR 1.2 for ever use.

          Results:

          Incident RA was associated with ever use of fonofos (OR = 1.70; 95% CI: 1.22, 2.37), carbaryl (OR = 1.51; 95% CI: 1.03, 2.23), and chlorimuron ethyl (OR = 1.45; 95% CI: 1.01, 2.07) compared with never use. Statistically significant exposure–response trends in association with RA were observed for lifetime days of use of atrazine [ OR tertile 3 = 1.62 (95% CI: 1.09, 2.40); p trend = 0.01 ] and toxaphene [ OR tertile 3 = 2.42 (95% CI: 1.03, 5.68); p trend = 0.02 ]. Exposure–response was nonlinear for fonofos [ OR tertile 1 = 2.27 (95% CI: 1.44, 3.57); OR tertile 2 = 0.98 (95% CI: 0.54, 1.80); OR tertile 3 = 2.10 (95% CI: 1.32, 3.36); p trend = 0.005 ] and suggestive for carbaryl ( p trend = 0.053 ).

          Conclusions:

          Our results provide novel evidence of associations between exposure to some pesticides and RA in male farmers. https://doi.org/10.1289/EHP1013

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          Most cited references46

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          Pesticides and human chronic diseases: evidences, mechanisms, and perspectives.

          Along with the wide use of pesticides in the world, the concerns over their health impacts are rapidly growing. There is a huge body of evidence on the relation between exposure to pesticides and elevated rate of chronic diseases such as different types of cancers, diabetes, neurodegenerative disorders like Parkinson, Alzheimer, and amyotrophic lateral sclerosis (ALS), birth defects, and reproductive disorders. There is also circumstantial evidence on the association of exposure to pesticides with some other chronic diseases like respiratory problems, particularly asthma and chronic obstructive pulmonary disease (COPD), cardiovascular disease such as atherosclerosis and coronary artery disease, chronic nephropathies, autoimmune diseases like systemic lupus erythematous and rheumatoid arthritis, chronic fatigue syndrome, and aging. The common feature of chronic disorders is a disturbance in cellular homeostasis, which can be induced via pesticides' primary action like perturbation of ion channels, enzymes, receptors, etc., or can as well be mediated via pathways other than the main mechanism. In this review, we present the highlighted evidence on the association of pesticide's exposure with the incidence of chronic diseases and introduce genetic damages, epigenetic modifications, endocrine disruption, mitochondrial dysfunction, oxidative stress, endoplasmic reticulum stress and unfolded protein response (UPR), impairment of ubiquitin proteasome system, and defective autophagy as the effective mechanisms of action. Copyright © 2013 Elsevier Inc. All rights reserved.
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            Is Open Access

            Epidemiology and genetics of rheumatoid arthritis

            Chapter summary The prevalence of rheumatoid arthritis (RA) is relatively constant in many populations, at 0.5–1.0%. However, a high prevalence of RA has been reported in the Pima Indians (5.3%) and in the Chippewa Indians (6.8%). In contrast, low occurrences have been reported in populations from China and Japan. These data support a genetic role in disease risk. Studies have so far shown that the familial recurrence risk in RA is small compared with other autoimmune diseases. The main genetic risk factor of RA is the HLA DRB1 alleles, and this has consistently been shown in many populations throughout the world. The strongest susceptibility factor so far has been the HLA DRB1*0404 allele. Tumour necrosis factor alleles have also been linked with RA. However, it is estimated that these genes can explain only 50% of the genetic effect. A number of other non-MHC genes have thus been investigated and linked with RA (e.g. corticotrophin releasing hormone, oestrogen synthase, IFN-γ and other cytokines). Environmental factors have also been studied in relation to RA. Female sex hormones may play a protective role in RA; for example, the use of the oral contraceptive pill and pregnancy are both associated with a decreased risk. However, the postpartum period has been highlighted as a risk period for the development of RA. Furthermore, breastfeeding after a first pregnancy poses the greatest risk. Exposure to infection may act as a trigger for RA, and a number of agents have been implicated (e.g. Epstein–Barr virus, parvovirus and some bacteria such as Proteus and Mycoplasma). However, the epidemiological data so far are inconclusive. There has recently been renewed interest in the link between cigarette smoking and RA, and the data presented so far are consistent with and suggestive of an increased risk.
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              Mechanism of action of organophosphorus and carbamate insecticides.

              T Fukuto (1990)
              Organophosphorus and carbamate insecticides are toxic to insects and mammals by virtue of their ability to inactivate the enzyme acetylcholinesterase. This review addresses the mechanism of inhibition of acetylcholinesterase by organophosphorus and carbamate esters, focusing on structural requirements necessary for anticholinesterase activity. The inhibition of acetylcholinesterase by these compounds is discussed in terms of reactivity and steric effects. The role of metabolic activation or degradation in the overall intoxication process is also discussed.
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                Author and article information

                Journal
                Environ Health Perspect
                Environ. Health Perspect
                EHP
                Environmental Health Perspectives
                Environmental Health Perspectives
                0091-6765
                1552-9924
                14 July 2017
                July 2017
                : 125
                : 7
                : 077010
                Affiliations
                [ 1 ]Occupational and Environmental Health Branch, Public Health Institute, Federal University of Rio de Janeiro , Rio de Janeiro, Brazil
                [ 2 ]Epidemiology Branch, National Institute of Environmental Health Sciences, National Institutes of Health, Department of Health and Human Services , Research Triangle Park, North Carolina, USA
                [ 3 ]Occupational and Environmental Epidemiology Branch, Division of Cancer Epidemiology and Genetics, National Cancer Institute, National Institutes of Health, Department of Health and Human Services , Bethesda, Maryland, USA
                Author notes
                Address correspondence to C.G. Parks, Epidemiology Branch, A3-05, National Institite of Environmental Health Sciences, National Institutes of Health, PO Box 12233, Research Triangle Park, NC 27599 USA; Telephone: (919) 541-2577; Email: Parks1@ 123456mail.nih.gov
                Article
                EHP1013
                10.1289/EHP1013
                5744649
                28718769
                9dbf4147-e3c6-4afa-a1da-6d2f8de5b1ec

                EHP is an open-access journal published with support from the National Institute of Environmental Health Sciences, National Institutes of Health. All content is public domain unless otherwise noted.

                History
                : 24 August 2016
                : 19 January 2017
                : 13 February 2017
                Categories
                Research

                Public health
                Public health

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