Cancer Incidence among Male Pesticide Applicators in the Agricultural Health Study Cohort Exposed to Diazinon

Division of Cancer Epidemiology and Genetics, National Cancer Institute, National Institutes of Health, Department of Health and Human Services, Rockville, MD 20892, USA.
American Journal of Epidemiology (Impact Factor: 5.23). 01/2006; 162(11):1070-9. DOI: 10.1093/aje/kwi321
Source: PubMed


Little is known about the potential carcinogenicity associated with routine application of diazinon, a common organophosphate insecticide. The authors explored a possible association of diazinon exposure with cancer risk in the Agricultural Health Study, a prospective cohort of licensed pesticide applicators in Iowa and North Carolina enrolled in 1993-1997. A total of 23,106 male applicators provided information in a self-administered questionnaire. Among 4,961 applicators who reported using diazinon, 301 incident cancer cases were diagnosed during the follow-up period ending December 2002 compared with 968 cases among 18,145 participants who reported no use. Poisson regression was used to calculate rate ratios and 95% confidence intervals. Two quantitative exposure metrics were used: lifetime exposure days and intensity-weighted lifetime exposure days, a measure that incorporates probability of pesticide exposure with lifetime pesticide application frequency. When lifetime exposure days were used, increased risks for the highest tertile of exposure and significant tests for trend for lung cancer and leukemia were observed. No other cancer site showed an association with diazinon for the highest tertile of exposure. Because these results were based on small numbers, additional analyses are necessary as more cases accrue to clarify whether diazinon is associated with cancer risk in humans.

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Available from: Michael C Alavanja, Oct 10, 2015
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    • "Recent studies cite a wide range of direct and indirect negative impacts of diazinon on aquatic biota, including dramatic reduction of zooplankton (Giddings et al. 1996); possible lethal effects on fish (Máchová et al. 2007; El-Sherif et al. 2009) and amphibians (Sparling and Fellers 2007); disruption of behavior patterns (Scholz et al. 2000); reduction in phytoplankton and periphyton (Relyea 2009); sublethal effects on olfactory functions (Moore and Waring 1996); changes in the erythocyte and leucocyte profile in fish probably due to the disruption of hematopoiesis or a decrease in non-specific immunity (Adedeji et al. 2009); cytotoxicity, endocrine disruption (Bisson and Hontela 2002); and indirect effects on growth and metamorphosis of tadpoles due to direct effects on zooplankton, phytoplankton, and periphyton (Relyea 2009). In addition, diazinon is listed as potentially carcinogenic (Beane Freeman et al. 2005). Crayfish, as representatives of large crustaceans, are ecologically important benthic macroinvertebrates, and are often key species in both still and running waters (Momot 1995). "
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    ABSTRACT: Diazinon is a widely applied agricultural pesticide whose effect importantly on the environment and the possible contamination of surface waters has led to increased interest in toxicological studies. Crayfish, as an ecologically important benthic macroinvertebrate, seems to be an appropriate model organism for such assessments. Acute toxicity tests were carried out on three crayfish age groups: young-of-the-year (total length = 25.0 ± 4.9 mm), juvenile (total length = 56.5 ± 3.8 mm) and adult (total length = 83.5 ± 5.7 mm). Young-of-the-year crayfish were found to be the most sensitive to diazinon (96 h LC50 = 0.15 mg L−1), followed by juvenile crayfish (96 h LC50 = 0.27 mg L−1), and adults (96 h LC50 = 0.51 mg L−1). Crayfish were highly sensitive to diazinon. A delayed effect of Diazinon 60EC on adults was detected (144 h LC50 = 0.44 mg L−1) suggests functional damage from the use of sublethal concentrations.
    International journal of Environmental Science and Technology 05/2013; 10(3). DOI:10.1007/s13762-013-0185-4 · 2.19 Impact Factor
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    • "Seven of these 19 pesticides are no longer registered for use in Canada or the United States (chlordane, dieldrin, fonofos, heptachlor, lindane , methyl bromide, and toxaphene), and three additional pesticides, alachlor, aldicarb, and metolachlor, are registered for use in the United States but are not registered in Canada. Of the remaining pesticides currently registered for use in Canada or the United States, statistically significant exposure–response trends were observed for alachlor (all lymphohematopoietic ), aldicarb (colon), carbaryl (melanoma), chlorpyrifos (lung, rectal), diazinon (all cancers, all lympho hemato poietic, leukemia, lung), dicamba (colon, lung), EPTC (all cancers, colon, pancreas), imazethapyr (bladder, colon), metolachlor (lung), pendimethalin (lung, pancreas, rectal), permethrin (multiple myeloma), and tri fluralin (colon) (Alavanja et al. 2004; Andreotti et al. 2009; Beane Freeman et al. 2005; Hou et al. 2006; Kang et al. 2008; Koutros et al. 2009; Lee et al. 2004a, 2004b, 2007b; Mahajan et al. 2007; Rusiecki et al. 2006, 2009; Samanic et al. 2006; van Bemmel et al. 2008). These pesticides are listed in Table 2 along with animal toxicologic evidence of carcinogenicity noted by the U.S. EPA (2007), Canadian Pest Management Regulatory Agency (PMRA) (Health Canada 2003, 2005, 2007, 2008), and the International Agency for Research on Cancer (IARC 2010). "
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    ABSTRACT: We reviewed epidemiologic evidence related to occupational pesticide exposures and cancer incidence in the Agricultural Health Study (AHS) cohort. Studies were identified from the AHS publication list available at as well as through a Medline/PubMed database search in March 2009. We also examined citation lists. Findings related to lifetime-days and/or intensity-weighted lifetime-days of pesticide use are the primary focus of this review, because these measures allow for the evaluation of potential exposure-response relationships. We reviewed 28 studies; most of the 32 pesticides examined were not strongly associated with cancer incidence in pesticide applicators. Increased rate ratios (or odds ratios) and positive exposure-response patterns were reported for 12 pesticides currently registered in Canada and/or the United States (alachlor, aldicarb, carbaryl, chlorpyrifos, diazinon, dicamba, S-ethyl-N,N-dipropylthiocarbamate, imazethapyr, metolachlor, pendimethalin, permethrin, trifluralin). However, estimates of association for specific cancers were often imprecise because of small numbers of exposed cases, and clear monotonic exposure-response patterns were not always apparent. Exposure misclassification is also a concern in the AHS and may limit the analysis of exposure-response patterns. Epidemiologic evidence outside the AHS remains limited with respect to most of the observed associations, but animal toxicity data support the biological plausibility of relationships observed for alachlor, carbaryl, metolachlor, pendimethalin, permethrin, and trifluralin. Continued follow-up is needed to clarify associations reported to date. In particular, further evaluation of registered pesticides is warranted.
    Environmental Health Perspectives 05/2010; 118(8):1117-25. DOI:10.1289/ehp.0901731 · 7.98 Impact Factor
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    • "Cakir and Sarikaya , 2005 , ( 9 ) Liu et al . , 2009 , ( 10 ) Osaba et al . , 2002 , ( 11 ) Mouchet et al . , 2006 , ( 12 ) Khan and Sinha , 1994 , ( 13 ) Fei and Ethell , 2008 , ( 14 ) Calviello et al . , 2006 , ( 15 ) Lee et al . , 2004 , ( 16 ) Beane Freeman et al . , 2005 , ( 18 ) Petri et al . , 2006 , ( 19 ) Mills et al . , 2005 , ( 20 ) Whalen et al . , 2003 , ( 21 ) McDuffie et al . , 2001 , ( 22 ) Mills , 1998 , ( 23 ) Ohnishi et al . , 2008 , ( 25 ) Sekine et al . , 2004 , ( 26 ) Xue et al . , 2005 , ( 27 ) Cecconi et al . , 2007 , ( 28 ) Subramoniam et al . , 1991 . Pellets were then suspended in "
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    ABSTRACT: Defining the impact on health of exposure to a low-dose pesticide mixture via food intake is a topical question since epidemiological studies suggest that this may increase the risk of pathologies and particularly haematopoietic malignancies. Here we investigated on the haematopoietic system of mice, the effect of a mixture of six pesticides frequently ingested through the intake of fruits and vegetables produced in France (alachlor, captan, diazinon, endosulfan, maneb, mancozeb). The mixture was administered repeatedly by gavage to mice for 4 weeks at levels derived from the human Acceptable Daily Intake (ADI) level adapted to the mean weight of mice. Using a NMR-based metabonomic approach, we show that this treatment led to specific gender-linked variations in the level of hepatic metabolites involved in oxidative stress and in the regulation of glucose metabolism, indicating a metabolic signature for this repeated administration. Interestingly, exposure to the low-dose pesticide mixture induced significant changes in the blood cell counts with modifications in the clonogenic and differentiating capacities of haematopoietic progenitors showing abnormalities in the granulocytic and monocytic lineages in female and male mice, respectively. From a molecular point of view, the changes induced by the pesticide treatment correlated with modifications of the PI 3-kinase/Akt signalling pathway, the tyrosine kinase Pyk2 and the c-Myc transcription factor, which are involved in the balance between self-renewal and differentiation of haematopoietic stem cells. Our results point to a significant effect of a very low dose of a mixture of commonly used pesticides on mice metabolism and haematopoietic system with major differences between males and females.
    Toxicology 10/2009; 267(1-3):80-90. DOI:10.1016/j.tox.2009.10.024 · 3.62 Impact Factor
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