Characterizing the Neurodevelopmental Pesticide Exposome in a Children’s Agricultural Cohort
Abstract
:1. Introduction
1.1. The Exposome
1.2. Aggregate Exposure Pathways (AEPs) and the Exposome
1.3. The Neurodevelopmental Exposome
1.4. Applying a Neurodevelopmental Exposome Framework to Evaluate the Potential Health Impacts of Pesticide Regulation
1.5. Using a Neurodevelopmental Exposome Framework to Characterize Pesticide Exposure in a Children’s Agricultural Cohort
2. Materials and Methods
2.1. Cohort Description and Sample Collection
2.2. Dust Analysis
2.3. Assessment of Potential Pesticide Neurotoxicity
2.4. Statistical Analysis
2.4.1. Heat Map Generation
2.4.2. Farmworker vs. Non-farmworker Comparisons
2.4.3. Comparisons across Time
3. Results
3.1. Categorization of Potentially Neurotoxic Pesticides
3.2. Neurodevelopmental Exposome Heat Map
3.3. Trends in Potentially Neurotoxic Pesticides
3.3.1. Unweighted Analysis
3.3.2. Weighted Analysis
3.4. Trends in Non-Neurotoxic Pesticides
4. Discussion
4.1. The Neurodevelopmental Exposome of Farmworkers and Non-farmworkers became More Similar over Time
4.2. Weighted Analysis Reveals a Greater Decline in the Levels of More Potent Potentially Neurotoxic Pesticides with Time
4.3. Limitations
5. Conclusions
Author Contributions
Funding
Acknowledgments
Conflicts of Interest
References
- Wild, C.P. Complementing the genome with an “exposome”: The outstanding challenge of environmental exposure measurement in molecular epidemiology. Cancer Epidemiol. Biomarkers Prev. 2005, 14, 1847–1850. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Miller, G.W.; Jones, D.P. The Nature of Nurture: Refining the Definition of the Exposome. Toxicol. Sci. 2014, 137, 1–2. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Jones, D.P. Sequencing the exposome: A call to action. Toxicol. Rep. 2016, 3, 29–45. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Rappaport, S.M.; Smith, M.T. Environment and Disease Risks. Science 2010, 330, 460–461. [Google Scholar] [CrossRef] [Green Version]
- Slama, R.; Vrijheid, M. Some challenges of studies aiming to relate the Exposome to human health. Occup. Environ. Med. 2015, 72, 383–384. [Google Scholar] [CrossRef]
- Wild, C.P. The exposome: From concept to utility. Int. J. Epidemiol. 2012, 41, 24–32. [Google Scholar] [CrossRef]
- Faustman, E.M.; Cannon, R.E.; Costa, L.; Eaton, D.L. Gene–Environment Interactions: Fundamentals of Ecogenetics. Environ. Health Perspect. 2006, 114, A382. [Google Scholar]
- Turner, T.N.; Hormozdiari, F.; Duyzend, M.H.; McClymont, S.A.; Hook, P.W.; Iossifov, I.; Raja, A.; Baker, C.; Hoekzema, K.; Stessman, H.A.; et al. Genome Sequencing of Autism-Affected Families Reveals Disruption of Putative Noncoding Regulatory DNA. Am. J. Hum. Genet. 2016, 98, 58–74. [Google Scholar] [CrossRef] [Green Version]
- Breton, C.V.; Marsit, C.J.; Faustman, E.; Nadeau, K.; Goodrich, J.M.; Dolinoy, D.C.; Herbstman, J.; Holland, N.; LaSalle, J.M.; Schmidt, R.; et al. Small-Magnitude Effect Sizes in Epigenetic End Points are Important in Children’s Environmental Health Studies: The Children’s Environmental Health and Disease Prevention Research Center’s Epigenetics Working Group. Environ. Health Perspect. 2017, 125, 511–526. [Google Scholar] [CrossRef] [PubMed]
- Buck Louis, G.M.; Yeung, E.; Sundaram, R.; Laughon, S.K.; Zhang, C. The Exposome—Exciting Opportunities for Discoveries in Reproductive and Perinatal Epidemiology: Exposome and reproductive and perinatal epidemiology. Paediatr. Perinat. Epidemiol. 2013, 27, 229–236. [Google Scholar] [CrossRef] [Green Version]
- Shaffer, R.M.; Smith, M.N.; Faustman, E.M. Developing the Regulatory Utility of the Exposome: Mapping Exposures for Risk Assessment through Lifestage Exposome Snapshots (LEnS). Environ. Health Perspect. 2017, 125, UNSP 085003. [Google Scholar] [CrossRef]
- Teeguarden, J.G.; Tan, Y.-M.; Edwards, S.W.; Leonard, J.A.; Anderson, K.A.; Corley, R.A.; Kile, M.L.; Simonich, S.M.; Stone, D.; Tanguay, R.L.; et al. Completing the Link between Exposure Science and Toxicology for Improved Environmental Health Decision Making: The Aggregate Exposure Pathway Framework. Environ. Sci. Technol. 2016, 50, 4579–4586. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Selevan, S.G.; Kimmel, C.A.; Mendola, P. Identifying critical windows of exposure for children’s health. Environ. Health Perspect. 2000, 108, 451–455. [Google Scholar] [PubMed]
- Stiles, J.; Jernigan, T.L. The Basics of Brain Development. Neuropsychol. Rev. 2010, 20, 327–348. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Grandjean, P.; Landrigan, P.J. Neurobehavioural effects of developmental toxicity. Lancet Neurol. 2014, 13, 330–338. [Google Scholar] [CrossRef] [Green Version]
- Tyler, C.V.; White-Scott, S.; Ekvall, S.M.; Abulafia, L. Environmental Health and Developmental Disabilities: A Life Span Approach. Fam. Community Health 2008, 31, 287–304. [Google Scholar] [CrossRef]
- Bouchard, M.F.; Bellinger, D.C.; Wright, R.O.; Weisskopf, M.G. Attention-Deficit/Hyperactivity Disorder and Urinary Metabolites of Organophosphate Pesticides. Pediatrics 2010, 125, e1270–e1277. [Google Scholar] [CrossRef] [Green Version]
- Engel, S.M.; Wetmur, J.; Chen, J.; Zhu, C.; Barr, D.B.; Canfield, R.L.; Wolff, M.S. Prenatal Exposure to Organophosphates, Paraoxonase 1, and Cognitive Development in Childhood. Environ. Health Perspect. 2011, 119, 1182–1188. [Google Scholar] [CrossRef] [Green Version]
- Rauh, V.; Arunajadai, S.; Horton, M.; Perera, F.; Hoepner, L.; Barr, D.B.; Whyatt, R. Seven-Year Neurodevelopmental Scores and Prenatal Exposure to Chlorpyrifos, a Common Agricultural Pesticide. Environ. Health Perspect. 2011, 119, 1196–1201. [Google Scholar] [CrossRef]
- Crosby, E.B.; Bailey, J.M.; Oliveri, A.N.; Levin, E.D. Neurobehavioral impairments caused by developmental imidacloprid exposure in zebrafish. Neurotoxicol. Teratol. 2015, 49, 81–90. [Google Scholar] [CrossRef] [Green Version]
- Cargill, C. Agriculture: The Cornerstone of Washington’s Economy 2016; Washington Policy Center: Seattle, WA, USA, 2016. [Google Scholar]
- Washington State Department of Commerce Agriculture and Food Manufacturing. Available online: http://choosewashingtonstate.com/why-washington/our-key-sectors/agriculture-food-processing/ (accessed on 7 January 2020).
- Cooper, J.; Dobson, H. The benefits of pesticides to mankind and the environment. Crop Prot. 2007, 26, 1337–1348. [Google Scholar] [CrossRef]
- Goldberger, J.R.; Lehrer, N.; Brunner, J.F. Azinphos-methyl (AZM) phase-out: Actions and attitudes of apple growers in Washington State. Renew. Agric. Food Syst. 2011, 26, 276–286. [Google Scholar] [CrossRef]
- US EPA Azinphos-Methyl Phase-out|Pesticides|US EPA. Available online: https://archive.epa.gov/pesticides/reregistration/web/html/phaseout_fs.html (accessed on 5 November 2019).
- Doerr, M.D.; Brunner, J.F.; Granger, K.R. Incorporating Organophosphate Alternative Insecticides Into Codling Moth Management Programs in Washington Apple Orchards. J. Integ. Pest Manag. 2012, 3, 1–4. [Google Scholar] [CrossRef] [Green Version]
- Washington State University Extension. Crop Protection Guide for Tree Fruits in Washington; Washington State University: Pullman, WA, USA, 2019. [Google Scholar]
- Tamaro, C.M.; Smith, M.N.; Workman, T.; Griffith, W.C.; Thompson, B.; Faustman, E.M. Characterization of organophosphate pesticides in urine and home environment dust in an agricultural community. Biomarkers 2018, 23, 174–187. [Google Scholar] [CrossRef] [PubMed]
- Smith, M.N.; Workman, T.; McDonald, K.M.; Vredevoogd, M.A.; Vigoren, E.M.; Griffith, W.C.; Thompson, B.; Coronado, G.D.; Barr, D.; Faustman, E.M. Seasonal and occupational trends of five organophosphate pesticides in house dust. J. Exposure Sci.Environ. Epidemiol. 2017, 27, 372–378. [Google Scholar] [CrossRef] [PubMed]
- Stanaway, I.B.; Wallace, J.C.; Shojaie, A.; Griffith, W.C.; Hong, S.; Wilder, C.S.; Green, F.H.; Tsai, J.; Knight, M.; Workman, T.; et al. Human Oral Buccal Microbiomes Are Associated with Farmworker Status and Azinphos-Methyl Agricultural Pesticide Exposure. Appl. Environ. Microbiol. 2017, 83, e02149-16. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Bennett, B.; Workman, T.; Smith, M.N.; Griffith, W.C.; Thompson, B.; Faustman, E.M. Longitudinal, Seasonal, and Occupational Trends of Multiple Pesticides in House Dust. Environ. Health Perspect. 2019, 127, 017003. [Google Scholar] [CrossRef]
- Thompson, B.; Coronado, G.D.; Vigoren, E.M.; Griffith, W.C.; Fenske, R.A.; Kissel, J.C.; Shirai, J.H.; Faustman, E.M. Para niños saludables: A community intervention trial to reduce organophosphate pesticide exposure in children of farmworkers. Environ. Health Perspect. 2008, 116, 687–694. [Google Scholar] [CrossRef] [Green Version]
- Smith, M.N.; Grice, J.; Cullen, A.; Faustman, E.M. A Toxicological Framework for the Prioritization of Children’s Safe Product Act Data. Int. J. Environ. Res. Public Health 2016, 13, 431. [Google Scholar] [CrossRef] [Green Version]
- Liu, P.; Wu, C.; Chang, X.; Qi, X.; Zheng, M.; Zhou, Z. Assessment of chlorpyrifos exposure and absorbed daily doses among infants living in an agricultural area of the Province of Jiangsu, China. Int. Arch. Occup. Environ. Health 2014, 87, 753–762. [Google Scholar] [CrossRef]
- Driver, J.; Ross, J.; Pandian, M.; Assaf, N.; Osimitz, T.; Holden, L. Evaluation of predictive algorithms used for estimating potential postapplication, nondietary ingestion exposures to pesticides associated with children’s hand-to-mouth behavior. J. Toxicol. Environ. Health Part A 2013, 76, 556–586. [Google Scholar] [CrossRef] [PubMed]
- Black, K.; Shalat, S.L.; Freeman, N.C.G.; Jimenez, M.; Donnelly, K.C.; Calvin, J.A. Children’s mouthing and food-handling behavior in an agricultural community on the US/Mexico border. J. Exposure Anal. Environ. Epidemiol. 2005, 15, 244–251. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Freeman, N.C.G.; Hore, P.; Black, K.; Jimenez, M.; Sheldon, L.; Tulve, N.; Lioy, P.J. Contributions of children’s activities to pesticide hand loadings following residential pesticide application. J. Exposure Anal. Environ. Epidemiol. 2005, 15, 81–88. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Freeman, N.C.; Jimenez, M.; Reed, K.J.; Gurunathan, S.; Edwards, R.D.; Roy, A.; Adgate, J.L.; Pellizzari, E.D.; Quackenboss, J.; Sexton, K.; et al. Quantitative analysis of children’s microactivity patterns: The Minnesota Children’s Pesticide Exposure Study. J. Exposure Anal. Environ. Epidemiol. 2001, 11, 501–509. [Google Scholar] [CrossRef] [Green Version]
- Zartarian, V.G.; Streicker, J.; Rivera, A.; Cornejo, C.S.; Molina, S.; Valadez, O.F.; Leckie, J.O. A pilot study to collect micro-activity data of two- to four-year-old farm labor children in Salinas Valley, California. J. Exposure Anal. Environ. Epidemiol. 1995, 5, 21–34. [Google Scholar] [PubMed]
- Pesticides Chemical Search|Chemical Search|Pesticides|US EPA. Available online: https://iaspub.epa.gov/apex/pesticides/f?p=chemicalsearch:1 (accessed on 29 October 2019).
- US EPA, ORD Guidelines for Neurotoxicity Risk Assessment. Available online: https://www.epa.gov/risk/guidelines-neurotoxicity-risk-assessment (accessed on 29 October 2019).
- US EPA. Diazinon Revised Risk Assessment and Agreement with Registrants 2001. Available online: https://www.oda.state.ok.us/cps/epaagree.pdf (accessed on 5 July 2016).
- US EPA. OCSPP Chlorpyrifos. Available online: https://www.epa.gov/ingredients-used-pesticide-products/chlorpyrifos (accessed on 5 November 2019).
- US EPA. OCSPP Boscalid. Human Health Risk Assessment for Registration Review. Available online: https://oehha.ca.gov/media/downloads/crnr/usepachlorpyrifoshhriskassessment2016.pdf (accessed on 19 November 2019).
- Schug, T.T.; Blawas, A.M.; Gray, K.; Heindel, J.J.; Lawler, C.P. Elucidating the Links Between Endocrine Disruptors and Neurodevelopment. Endocrinology 2015, 156, 1941–1951. [Google Scholar] [CrossRef]
- US EPA, OCSPP Schedule for Review of Neonicotinoid Pesticides. Available online: https://www.epa.gov/pollinator-protection/schedule-review-neonicotinoid-pesticides (accessed on 5 November 2019).
- Griffith, W.C.; Vigoren, E.M.; Smith, M.N.; Workman, T.; Thompson, B.; Coronado, G.D.; Faustman, E.M. Application of improved approach to evaluate a community intervention to reduce exposure of young children living in farmworker households to organophosphate pesticides. J. Exposure Sci. Environ. Epidemiol. 2019, 29, 358–365. [Google Scholar] [CrossRef]
Compound | Identified as Neurotoxic | Reference Dose (mg/kg/Day) | Compound | Identified as Neurotoxic |
---|---|---|---|---|
2_4D | Y | 0.067 | 2_4DB | N |
Acetamiprid | Y | 0.1 | 2_4DP | N |
Aldicarb | Y | 0.001 | Boscalid | N |
Azinphosmethyl | Y | 0.0033 | Carfentrazone-ethyl | N |
Azoxystrobin | Y | 0.67 | Clofentezine | N |
Bifenazate | Y | 0.134 * | Diuron | N |
Carbaryl | Y | 0.01 | Dodine | N |
Carbofuran | Y | 0.00006 | Etoxazole | N |
Chlorpyrifos | Y | 0.005 | Fenarimol | N |
Clothianidin | Y | 0.025 | Fenhexamid | N |
Coumaphos | Y | 0.007 | Fenoxycarb | N |
Cyphenothrin | Y | 0.23 * | Fenpyroximate | N |
Deltamethrin | Y | 0.01 | Flumioxazin | N |
Diazinon | Y | 0.0025 | GibberellicAcid | N |
Dicamba | Y | 1 | Hexythiazox | N |
Dichlorvos | Y | 0.008 | Imazamox | N |
Dimethoate | Y | 0.013 | Imazapic | N |
Ethoprop | Y | 0.00025 | Imazapyr | N |
Etofenprox | Y | 0.57 * | Imazethapyr | N |
Imidacloprid | Y | 0.14 | Linuron | N |
Imiprothrin | Y | 0.33 ** | Mefenoxam | N |
Malathion | Y | 0.14 | Metribuzin | N |
MCPA | Y | 0.04 | Myclobutanil | N |
MCPP | Y | 1.75 | Na o Phenylphenate | N |
Methamidophos | Y | 0.003 | Norflurazon | N |
Methidathion | Y | 0.002 | Novaluron | N |
Methomyl ^ | Y | 0.05 * | Pendimethalin | N |
Methyl Parathion | Y | 0.0011 | Piperonyl Butoxide | N |
Naled | Y | 0.01 | Propargite | N |
Oxamyl | Y | 0.001 | Pyrimethanil | N |
Permethrin | Y | 0.25 | Pyriproxyfen | N |
Phorate | Y | 0.0025 | Quinclorac | N |
Phosmet | Y | 0.045 | Quinoxyfen | N |
Pirimicarb | Y | 0.04 * | S-Metolachlor | N |
Propiconazole | Y | 0.3 | Spinosyn A/D (spinosad) | N |
Propoxur | Y | 0.005 | Triclopyr | N |
Pyridaben | Y | 0.44 | Triclosan | N |
S-Bioallethrin ^^ | Y | 0.0013 *** | Trifloxystrobin | N |
Sumithrin | Y | 0.03 | Tetramethrin | N |
Tebuconazole | Y | 0.016 # | ||
Terbufos | Y | 0.0003 | ||
Tetrachlorvinphos | Y | 0.067 | ||
Thiacloprid | Y | 0.01 | ||
Thiamethoxam | Y | 0.35 | ||
Thiophanate methyl | Y | 0.4 | ||
Triadimefon | Y | 0.034 | ||
Triflumizole | Y | 0.25 |
Potentially Neurotoxic Pesticides | Non-Neurotoxic Pesticides | |||||||
---|---|---|---|---|---|---|---|---|
Proportions Tests | FW | NFW | Difference (95% CI) | p | FW | NFW | Difference (95% CI) | p |
Proportion Red 2005 | 0.38 | 0.11 | 0.27 (0.08–0.44) | 0.01 * | 0.18 | 0.11 | 0.07 (−0.10–0.22) | 0.46 |
Proportion Red 2011 | 0.15 | 0.20 | −0.5 (−0.22–0.12) | 0.57 | 0.38 | 0.26 | 0.12 (−0.09–0.33) | 0.28 |
Proportion Decreased (2005–2011) | 0.70 | 0.52 | 0.18 (−0.07–0.43) | 0.16 | 0.25 | 0.15 | 0.1 (−0.12–0.32) | 0.36 |
Potentially Neurotoxic Pesticides | Non-Neurotoxic Pesticides | |||||||
Mixed Effects Tests | Models | p | Models | p | ||||
Null vs. Time Fixed | log(pest) ~ 1 + (1|house) log(pest) ~ tm + (1|house) | 0.75 | log(pest) ~ 1 + (1|house) log(pest) ~ tm + (1|house) | <0.0001 *** | ||||
Time Fixed vs. Time*Occupation | log(pest) ~ tm + (1|house) log(pest) ~ tm*occ + (1|house) | 0.0005 *** | log(pest) ~ tm + (1|house) log(pest) ~ tm*occ + (1|house) | 0.98 | ||||
Null vs. Time Fixed w/in Occupation | ||||||||
FW | log(pest) ~ 1 + (1|house) log(pest) ~ tm + (1|house) | 0.57 | log(pest) ~ 1 + (1|house) log(pest) ~ tm + (1|house) | <0.0001 *** | ||||
NFW | log(pest) ~ 1 + (1|house) log(pest) ~ tm + (1|house) | 0.28 | log(pest) ~ 1 + (1|house) log(pest) ~ tm + (1|house) | <0.0001 *** |
Potentially Neurotoxic Pesticides (Unweighted) | Potentially Neurotoxic Pesticides (Weighted) | |||||||
---|---|---|---|---|---|---|---|---|
Proportions Tests | FW | NFW | Difference (95% CI) | p | FW | NFW | Difference (95% CI) | p |
Proportion Red 2005 | 0.38 | 0.11 | 0.27 (0.08–0.44) | 0.01 ** | 0.43 | 0.06 | 0.37 (0.20–0.54) | <0.001 *** |
Proportion Red 2011 | 0.15 | 0.20 | −0.5 (−0.22–0.12) | 0.57 | 0.07 | 0.04 | 0.03 (−0.08–0.14) | 0.62 |
Potentially Neurotoxic Pesticides (Unweighted) | Potentially Neurotoxic Pesticides (Weighted) | |||||||
Mixed Effects Tests | Models | p | Models | p | ||||
Null vs. Time Fixed | log(pest) ~ 1 + (1|house) log(pest) ~ tm + (1|house) | 0.75 | log(pest) ~ 1 + (1|house) log(pest) ~ tm + (1|house) | 0.004 ** | ||||
Time Fixed vs. Time*Occupation | log(pest) ~ tm + (1|house) log(pest) ~ tm*occ + (1|house) | 0.0005 *** | log(pest) ~ tm + (1|house) log(pest) ~ tm*occ + (1|house) | <0.001 ** | ||||
Null vs. Time Fixed w/in Occupation | ||||||||
FW | log(pest) ~ 1 + (1|house) log(pest) ~ tm + (1|house) | 0.57 | log(pest) ~ 1 + (1|house) log(pest) ~ tm + (1|house) | 0.001 ** | ||||
NFW | log(pest) ~ 1 + (1|house) log(pest) ~ tm + (1|house) | 0.28 | log(pest) ~ 1 + (1|house) log(pest) ~ tm + (1|house) | 0.38 |
© 2020 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (http://creativecommons.org/licenses/by/4.0/).
Share and Cite
Bennett, B.; Workman, T.; Smith, M.N.; Griffith, W.C.; Thompson, B.; Faustman, E.M. Characterizing the Neurodevelopmental Pesticide Exposome in a Children’s Agricultural Cohort. Int. J. Environ. Res. Public Health 2020, 17, 1479. https://doi.org/10.3390/ijerph17051479
Bennett B, Workman T, Smith MN, Griffith WC, Thompson B, Faustman EM. Characterizing the Neurodevelopmental Pesticide Exposome in a Children’s Agricultural Cohort. International Journal of Environmental Research and Public Health. 2020; 17(5):1479. https://doi.org/10.3390/ijerph17051479
Chicago/Turabian StyleBennett, Breana, Tomomi Workman, Marissa N. Smith, William C. Griffith, Beti Thompson, and Elaine M. Faustman. 2020. "Characterizing the Neurodevelopmental Pesticide Exposome in a Children’s Agricultural Cohort" International Journal of Environmental Research and Public Health 17, no. 5: 1479. https://doi.org/10.3390/ijerph17051479