Household Organophosphorus Pesticide Use and Parkinson's Disease

Published by Oxford University Press on behalf of the International Epidemiological Association International Journal of Epidemiology 2013;42:1476–1485 ß The Author 2013; all rights reserved. Advance Access publication 20 September 2013 doi:10.1093/ije/dyt170 Household organophosphorus pesticide use and Parkinson’s disease Shilpa Narayan,1 Zeyan Liew,1 Kimberly Paul,1 Pei-Chen Lee,1 Janet S Sinsheimer,2 Jeff M Bronstein3 and Beate Ritz1,3* 1Department of Epidemiology, Fielding School of Public Health, UCLA, Los Angeles, CA, USA, 2Departments of Human Genetics and Biomathematics, David Geffen School of Medicine, and Department of Biostatistics, Fielding School of Public Health, UCLA, Los Angeles, CA, USA and 3Department of Neurology, School of Medicine, UCLA, Los Angeles, CA, USA *Corresponding author. Department of Epidemiology, Fielding SPH, UCLA, 650 Charles E. Young Drive, Los Angeles, CA 90095-1772, USA. E-mail: [email protected] Downloaded from Accepted 24 July 2013 Background Household pesticide use is widespread in the USA. Since the 1970s, http://ije.oxfordjournals.org/ organophosphorus chemicals (OPs) have been common active ingredients in these products. Parkinson’s disease (PD) has been linked to pesticide exposures but little is known about the contri- butions of chronic exposures to household pesticides. Here we investigate whether long-term use of household pesticides, especially those containing OPs, increases the odds of PD. Methods In a population-based case-control study, we assessed frequency of household pesticide use for 357 cases and 807 controls, relying on at University of California, Los Angeles on May 12, 2015 the California Department of Pesticide Regulation product label database to identify ingredients in reported household pesticide products and the Pesticide Action Network pesticide database of chemical ingredients. Using logistic regression we estimated the effects of household pesticide use. Results Frequent use of any household pesticide increased the odds of PD by 47% [odds ratio (OR) ¼ 1.47, (95% confidence interval (CI): 1.13, 1.92)]; frequent use of products containing OPs increased the odds of PD more strongly by 71% [OR ¼ 1.71, (95% CI: 1.21, 2.41)] and frequent organothiophosphate use almost doubled the odds of PD. Sensitivity analyses showed that estimated effects were independ- ent of other pesticide exposures (ambient and occupational) and the largest odds ratios were estimated for frequent OP users who were carriers of the 192QQ paraoxonase genetic variant related to slower detoxification of OPs. Conclusions We provide evidence that household use of OP pesticides is associated with an increased risk of developing PD. Keywords Environmental exposures, household pesticide use, organophosphorus pesticides, paraoxonase, Parkinson’s disease, United States, California Introduction dopaminergic neurons in the midbrain and presence Parkinson’s disease (PD) is a neurodegenerative of Lewy bodies. Pesticides in general have been asso- disease characterized clinically by both motor and ciated with an increased risk for developing PD1 but non-motor symptoms and pathologically by loss of most human studies focused on occupational 1476 HOUSEHOLD PESTICIDES AND PARKINSON’S DISEASE 1477 exposures.2,3 Household pesticide use in the USA con- neighbouring households and enrolled participants tinues to be very common, with use prevalence as during in-person visits at their doorstep. Control sam- high as 80–90% of households.4–6 This is of concern pling strategies have been described in detail since persistence of pesticides inside homes can lead elsewhere.18,23 to prolonged exposures of household members.7–9 Of 1212 potential controls contacted through the Until recently, many pesticide products permitted for first recruitment strategy, 457 were ineligible (409 household use contained organophosphorus (OP) were <35 years of age, 44 were too ill to participate chemicals; e.g. the OP insecticides chlorpyrifos and and 4 did not reside in target counties). Furthermore, diazinon were widely used in household applications 409 eligible controls declined, became too ill or moved prior to the United States Environmental Protection after screening and prior to interview, leaving 346 Agency phase-out from products permitted for house- controls recruited via phone and mail. In addition, hold use in 2001 and 2004, respectively.10,11 an early mailing, for which the number of eligible Organophosphorus pesticides as a class and individual subjects who declined remains unknown, produced OPs such as chlorpyrifos and parathion have been 62 controls with home pesticide use information Downloaded from associated with PD in a handful of studies.12–16 from interviews. We screened 4756 individuals for eli- Here we explore whether exposures to pesticides gibility at their doorstep, finding 3515 to be ineligible from household use, especially those containing OPs, (88% due to age criteria) and leaving 1241 eligible impact the odds of developing PD. In addition, we controls, of whom 634 declined participation and also assess whether our results are consistent with 607 controls enrolled. However, 183 subjects agreed genetic susceptibility expected among carriers of the to an abbreviated questionnaire without household http://ije.oxfordjournals.org/ 192QQ and 55MM variants in the gene encoding the pesticide information and were excluded. xenobiotic enzyme paraoxonase (PON1) known to Of all cases and controls enrolled, in total 357 cases 17 detoxify several common OPs. and 807 controls provided information necessary for analyses of household pesticide use. For 278 cases and 397 controls of Caucasian race, we have both PON1 Methods genotype and household pesticide use information to assess modifications of OP pesticide effects on PD due The UCLA Institutional Review Board approved the to differences in OP metabolism from known func- at University of California, Los Angeles on May 12, 2015 study, and all participants provided written informed tional variants. consent. Subject recruitment and enrolment Exposure assessment This case-control study enrolled incident idiopathic Trained staff collected information on demographic PD patients from 2001 to 2007 and population-based characteristics, smoking history and lifetime house- controls between 2001 and 2011 from three mostly hold pesticide use. Participants self-reported personal rural agricultural counties (Kern, Tulare and Fresno) use of pesticide products during four age periods: in central California. Subject recruitment18,19 and case young adult (16–<25 years), adult (25–<45 years), criteria20,21 have been described elsewhere. middle age (45–<65 years), and senior (565 years) We identified 1167 PD patients through local in three micro-environments, i.e. inside the home, neurologists, medical groups and public service an- outdoors on lawns and in yards, or during gardening nouncements; 397 had received a PD diagnosis 43 activities. Subjects were asked to recall names of years prior to recruitment, 134 lived outside the products and the pesticide targets (e.g. cockroaches, area, 51 did not have a PD diagnosis and 22 were spiders, ants, termites, bees/hornets/wasps, flies, weed too ill to participate. Of all eligible cases (N ¼ 563), control, plant disease); some recalled specific chem- 90 could not be examined, i.e. declined, moved, icals (e.g. malathion, diazinon). We also elicited became too ill or died before we examined them. information about formulation of products (e.g. Our movement disorder neurologists examined 473 liquid, granules, bait, powder) and frequency of use, eligible patients and excluded 107, because they did i.e. none or rare (once a year or less), occasional (2–11 not meet required criteria for idiopathic PD.22 Six sub- times a year) or regular use (once a month or more; jects withdrew prior to interview. note: nobody reported more than once a week average Initially, we recruited controls from the population use). We prompted interviewees who recalled a por- using Medicare lists (in 2001) but, after the instate- tion of the product name with similarly sounding ment of the Health Insurance Portability and products with the same target and formulation. All Accountability Act (HIPAA), we solely used residen- interviews for cases and controls enrolled through tial tax assessor records from the tri-county area. Two our first sampling strategy were conducted from sampling strategies were implemented to maximize 2001 through 2007 and from 2009 through 2011 for control enrolment success: first, we randomly selected controls enrolled through our second strategy. residential parcels and enrolled via mail and phone, Throughout, we employed the same primary inter- and second, we randomly selected clusters of viewers and supervisors. 1478 INTERNATIONAL JOURNAL OF EPIDEMIOLOGY We supplemented our interview data with informa- tetrachlorvinphos) and organothiophosphates (e.g. tion about ingredients of reported home and garden chlorpyrifos, diazinon, malathion, oxydemeton- use pesticide products from the California Department methyl, parathion, demeton, disulfoton, methi- of Pesticide Regulation (CDPR) product label data- dathion) and finally (iv) the most commonly used base.24 Over 70% of products in this database have insecticides, diazinon and chlorpyrifos. registration dates from the year 1970 and later. We We also excluded exposures reported for the past 10 compared dates of active registration listed in the years prior to the index age to account for the ex- CDPR

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