Skip to main content
SpringerLink
Log in

Biomarkers of Sensitivity and Exposure in Washington State Pesticide Handlers

  • Conference paper
  • First Online:
Paraoxonases in Inflammation, Infection, and Toxicology

Part of the book series: Advances in Experimental Medicine and Biology ((AEMB,volume 660))

Abstract

Organophosphate (OP) and N-methyl-carbamate (CB) insecticides are widely used in agriculture in the US and abroad. These compounds – which inhibit acetylcholinestersase (AChE) enzyme activity – continue to be responsible for a high proportion of pesticide poisonings among US agricultural workers. It is possible that some individuals may be especially susceptible to health effects related to OP/CB exposure. The paraoxonase (PON1) enzyme metabolizes the highly toxic oxon forms of some OPs, and an individual’s PON1 status may be an important determinant of his or her sensitivity to these chemicals. This chapter discusses methods used to characterize the PON1 status of individuals and reviews previous epidemiologic studies that have evaluated PON1-related sensitivity to OPs in relation to various health endpoints. It also describes an ongoing longitudinal study among OP-exposed agricultural pesticide handlers who are participating in a recently implemented cholinesterase monitoring program in Washington State. This study will evaluate handlers’ PON1 status as a hypothesized determinant of butyrylcholinesterase (BuChE) inhibition. Such studies will be useful to determine how regulatory risk assessments might account for differences in PON1-related OP sensitivity when characterizing inter-individual variability in risk related to OP exposure. Recent work assessing newer and more sensitive biomarkers of OP exposure is also discussed briefly in this chapter.

This is a preview of subscription content, log in via an institution to check access.

Access this chapter

Log in via an institution
Chapter
USD 29.95
Price excludes VAT (USA)
  • Available as PDF
  • Read on any device
  • Instant download
  • Own it forever
eBook
USD 169.00
Price excludes VAT (USA)
  • Available as EPUB and PDF
  • Read on any device
  • Instant download
  • Own it forever
Softcover Book
USD 219.99
Price excludes VAT (USA)
  • Compact, lightweight edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info
Hardcover Book
USD 219.99
Price excludes VAT (USA)
  • Durable hardcover edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info

Tax calculation will be finalised at checkout

Purchases are for personal use only

Institutional subscriptions

References

  • Alavanja MC, Hoppin JA, Kamel F. Health effects of chronic pesticide exposure: cancer and neurotoxicity. Annu Rev Public Health 2004;25:155–197.

    Article  PubMed  Google Scholar 

  • Amitai G, Moorad D, Adani R, Doctor BP. Inhibition of acetylcholinesterase and butyrylcholinesterase by chlorpyrifos-oxon. Biochem Pharmacol 1998;56(3):293–299.

    Article  CAS  PubMed  Google Scholar 

  • Battuello K, Furlong CE, Fenske R, Austin MA, Burke W. Paraoxonase polymorphisms and susceptibility to organophosphate pesticides. In: Khoury MJ, Little J, Burke W (eds.). Human Genome Epidemiology: A Scientific Foundation for Using Genetic Information to Improve Health and Prevent Disease. New York: Oxford University Press; 2004.

    Google Scholar 

  • Brophy VH, Hastings MD, Clendenning JB, Richter RJ, Jarvik GP, Furlong CE. Polymorphisms in the human paraoxonase (PON1) promoter. Pharmacogenetics 2001;11(1):77–84.

    Article  CAS  PubMed  Google Scholar 

  • Brophy VH, Jampsa RL, Clendenning JB, McKinstry LA, Jarvik GP, Furlong CE. Effects of 5' regulatory-region polymorphisms on paraoxonase-gene (PON1) expression. Am J Hum Genet 2001;68(6):1428–1436.

    Article  CAS  PubMed  Google Scholar 

  • CalEPA. Report for the application and ambient air monitoring of chlorpyrifos (and the oxon analogue) in Tulare County during spring/summer, 1996. Sacramento, CA: California Environmental Protection Agency; 1998.

    Google Scholar 

  • Calvert GM, Karnik J, Mehler L, Beckman J, Morrissey B, Sievert J, et al. Acute pesticide poisoning among agricultural workers in the United States, 1998–2005. Am J Ind Med 2008;51(12):883–898

    Article  PubMed  Google Scholar 

  • ChESAC. Cholinesterase Monitoring of Pesticide Handlers in Agriculture: 2004–2006. Olympia, WA: Scientific Advisory Committee for Cholinesterase Monitoring; 2006 November 13.

    Google Scholar 

  • Cholinesterase Monitoring. In: Washington Administrative Code, Chapter 296–307, Part J-1; 2004.

    Google Scholar 

  • Cole TB, Walter BJ, Shih DM, Tward AD, Lusis AJ, Timchalk C, et al. Toxicity of chlorpyrifos and chlorpyrifos oxon in a transgenic mouse model of the human paraoxonase (PON1) Q192R polymorphism. Pharmacogenet Genomics 2005;15(8):589–598.

    Article  CAS  PubMed  Google Scholar 

  • Costa LG, Cole TB, Vitalone A, Furlong CE. Measurement of paraoxonase (PON1) status as a potential biomarker of susceptibility to organophosphate toxicity. Clin Chim Acta 2005;352(1–2):37–47.

    Article  CAS  PubMed  Google Scholar 

  • Durrington PN, Mackness B, Mackness MI. The hunt for nutritional and pharmacological modulators of paraoxonase. Arterioscler Thromb Vasc Biol 2002;22(8):1248–1250.

    Article  CAS  PubMed  Google Scholar 

  • Eckerson HW, Wyte CM, La Du BN. The human serum paraoxonase/arylesterase polymorphism. Am J Hum Genet 1983;35(6):1126–1138.

    CAS  PubMed  Google Scholar 

  • Ecobichon DJ. Toxic effects of pesticides. In: Klaassen CD (ed.). Casarett and Doull’s Toxicology: The Basic Science of Poisons. 6th ed. New York: McGraw-Hill; 2001. 763–810.

    Google Scholar 

  • Ferre N, Camps J, Fernandez-Ballart J, Arija V, Murphy MM, Ceruelo S, et al. Regulation of serum paraoxonase activity by genetic, nutritional, and lifestyle factors in the general population. Clin Chem 2003;49(9):1491–1497.

    Article  CAS  PubMed  Google Scholar 

  • Furlong CE, Costa LG, Hassett C, Richter RJ, Sundstrom JA, Adler DA, et al. Human and rabbit paraoxonases: purification, cloning, sequencing, mapping and role of polymorphism in organophosphate detoxification. Chemico-Biological Interactions 1993;87(1–3):35–48.

    Article  CAS  PubMed  Google Scholar 

  • Furlong CE, Holland N, Richter RJ, Bradman A, Ho A, Eskenazi B. PON1 status of farmworker mothers and children as a predictor of organophosphate sensitivity. Pharmacogenetics and Genomics 2006;16(3):183–190.

    CAS  PubMed  Google Scholar 

  • Furlong CE, Li WF, Richter RJ, Shih DM, Lusis AJ, Alleva E, et al. Genetic and temporal determinants of pesticide sensitivity: role of paraoxonase (PON1). Neurotoxicology 2000;21(1–2):91–100.

    CAS  PubMed  Google Scholar 

  • Furlong CE, Richter RJ, Seidel SL, Costa LG, Motulsky AG. Spectrophotometric assays for the enzymatic hydrolysis of the active metabolites of chlorpyrifos and parathion by plasma paraoxonase/arylesterase. Anal Biochem 1989;180(2):242–247.

    Article  CAS  PubMed  Google Scholar 

  • Hofmann JN, Keifer MC, Furlong CE, De Roos AJ, Farin FM, Fenske RA, et al. Serum cholinesterase inhibition in relation to paraoxonase-1 (PON1) status among organophosphate-exposed agricultural pesticide handlers. Environ Health Perspect 2009;117(9)1402–1408.

    Google Scholar 

  • Jarvik GP, Jampsa R, Richter RJ, Carlson CS, Rieder MJ, Nickerson DA, et al. Novel paraoxonase (PON1) nonsense and missense mutations predicted by functional genomic assay of PON1 status. Pharmacogenetics 2003;13(5):291–295.

    Article  CAS  PubMed  Google Scholar 

  • Jarvik GP, Rozek LS, Brophy VH, Hatsukami TS, Richter RJ, Schellenberg GD, et al. Paraoxonase (PON1) phenotype is a better predictor of vascular disease than is PON1(192) or PON1(55) genotype. Arterioscler Thromb Vasc Biol 2000;20(11):2441–2447.

    CAS  PubMed  Google Scholar 

  • Jarvik GP, Tsai NT, McKinstry LA, Wani R, Brophy VH, Richter RJ, et al. Vitamin C and E intake is associated with increased paraoxonase activity. Arterioscler Thromb Vasc Biol 2002;22(8):1329–1333.

    Article  CAS  PubMed  Google Scholar 

  • Kalman D, van Belle G. 2007 Cholinesterase Analysis. URL: http://www.lni.wa.gov/Safety/Topics/AtoZ/Cholinesterase/files/report120307.pdf. Letter. Seattle, WA: University of Washington; 2007.

  • Kamel F, Engel LS, Gladen BC, Hoppin JA, Alavanja MC, Sandler DP. Neurologic symptoms in licensed private pesticide applicators in the agricultural health study. Environ Health Perspect 2005;113(7):877–882.

    Article  CAS  PubMed  Google Scholar 

  • Kamel F, Hoppin JA. Association of pesticide exposure with neurologic dysfunction and disease. Environ Health Perspect 2004;112(9):950–958.

    Article  CAS  PubMed  Google Scholar 

  • Lee BW, London L, Paulauskis J, Myers J, Christiani DC. Association between human paraoxonase gene polymorphism and chronic symptoms in pesticide-exposed workers. J Occup Environ Med 2003;45(2):118–122.

    Article  CAS  PubMed  Google Scholar 

  • Leviev I, James RW. Promoter polymorphisms of human paraoxonase PON1 gene and serum paraoxonase activities and concentrations. Arterioscler Thromb Vasc Biol 2000;20(2):516–521.

    CAS  PubMed  Google Scholar 

  • Li WF, Costa LG, Richter RJ, Hagen T, Shih DM, Tward A, et al. Catalytic efficiency determines the in-vivo efficacy of PON1 for detoxifying organophosphorus compounds. Pharmacogenetics 2000;10(9):767–779.

    Article  CAS  PubMed  Google Scholar 

  • Lotti M. Cholinesterase inhibition: complexities in interpretation. Clin Chem 1995;41(12 Pt 2):1814–1818.

    CAS  PubMed  Google Scholar 

  • Lotti M. Clinical toxicology of anticholinesterase agents in humans. In: Krieger R (ed.). Handbook of Pesticide Toxicology. 2nd ed. San Diego, CA: Academic Press; 2001. 1043–1085.

    Google Scholar 

  • Mackness B, Durrington P, Povey A, Thomson S, Dippnall M, Mackness M, et al. Paraoxonase and susceptibility to organophosphorus poisoning in farmers dipping sheep. Pharmacogenetics 2003;13(2):81–88.

    Article  CAS  PubMed  Google Scholar 

  • McCauley LA, Anger WK, Keifer M, Langley R, Robson MG, Rohlman D. Studying health outcomes in farmworker populations exposed to pesticides. Environ Health Perspect 2006;114(6):953–960.

    Article  CAS  PubMed  Google Scholar 

  • Nolan RJ, Rick DL, Freshour NL, Saunders JH. Chlorpyrifos: pharmacokinetics in human volunteers. Toxicol Appl Pharmacol 1984;73(1):8–15.

    Article  CAS  PubMed  Google Scholar 

  • Quistad GB, Klintenberg R, Casida JE. Blood acylpeptide hydrolase activity is a sensitive marker for exposure to some organophosphate toxicants. Toxicol Sci 2005;86(2):291–299.

    Article  CAS  PubMed  Google Scholar 

  • Reigart J, Roberts J. Recognition and Management of Pesticide Poisonings. 5th ed. Washington, DC: Environmental Protection Agency; 1999.

    Google Scholar 

  • Richards P, Johnson M, Ray D, Walker C. Novel protein targets for organophosphorus compounds. Chem Biol Interact 1999;119–120:503–511.

    Article  PubMed  Google Scholar 

  • Richter RJ, Furlong CE. Determination of paraoxonase (PON1) status requires more than genotyping. Pharmacogenetics 1999;9(6):745–753.

    Article  CAS  PubMed  Google Scholar 

  • Richter RJ, Jampsa R, Jarvik GP, Costa L, Furlong CE. Determination of paraoxonase 1 (PON1) status and genotypes at specific polymorphic sites. In: Mains M, Costa L, Reed D, Hodgson E (ed.). Current Protocols in Toxicology. New York, NY: John Wiley and Sons; 2004.

    Google Scholar 

  • Rothlein J, Rohlman D, Lasarev M, Phillips J, Muniz J, McCauley L. Organophosphate pesticide exposure and neurobehavioral performance in agricultural and non-agricultural Hispanic workers. Environ Health Perspect 2006;114(5):691–696.

    Article  CAS  PubMed  Google Scholar 

  • Shih DM, Gu L, Xia YR, Navab M, Li WF, Hama S, et al. Mice lacking serum paraoxonase are susceptible to organophosphate toxicity and atherosclerosis. Nature 1998;394(6690):284–287.

    Article  CAS  PubMed  Google Scholar 

  • Smith T. 2006 Crop Protection Guide for Tree Fruits in Washington. Pullman, WA: Washington State University Extension; 2006. Report No.: EB0419.

    Google Scholar 

  • Sozmen EY, Mackness B, Sozmen B, Durrington P, Girgin FK, Aslan L, et al. Effect of organophosphate intoxication on human serum paraoxonase. Hum Exp Toxicol 2002;21(5):247–252.

    Article  CAS  PubMed  Google Scholar 

  • Suehiro T, Nakamura T, Inoue M, Shiinoki T, Ikeda Y, Kumon Y, et al. A polymorphism upstream from the human paraoxonase (PON1) gene and its association with PON1 expression. Atherosclerosis 2000;150(2):295–298.

    Article  CAS  PubMed  Google Scholar 

  • WASS. Washington’s agricultural fruit chemical usage, 2007: Apples. Olympia, WA: Washington Agricultural Statistics Service; 2008.

    Google Scholar 

  • Wilson B. Cholinesterases. In: Krieger RI (ed.). Handbook of Pesticide Toxicology. San Diego: Academic Press; 2001. 967–985.

    Google Scholar 

  • Yuknavage KL, Fenske RA, Kalman DA, Keifer MC, Furlong CE. Simulated dermal contamination with capillary samples and field cholinesterase biomonitoring. J Toxicol Environ Health 1997;51(1):35–55.

    Article  CAS  PubMed  Google Scholar 

  • Zech R, Zurcher K. Organophosphate splitting serum enzymes in different mammals. Comp Biochem Physiol B 1974;48(3):427–433.

    Article  CAS  PubMed  Google Scholar 

  • WSUCE. Crop Profile for Hops in Washington. Richland, WA: Washington State University Cooperative Extension; 2001. Report No.: MISC0353E.

    Google Scholar 

  • WASS. Washington Ag Chemical Use. URL: http://www.nass.usda.gov/Statistics_by_State/Washington/Publications/Ag_Chemical_Use/index.asp. In. Olympia, WA: Washington Agricultural Statistics Service; Accessed December 2008.

  • USEPA. The use of data on cholinesterase inhibition for risk assessments of organophosphorous and carbamate pesticides. Washington, DC: Office of Pesticide Programs; 2000.

    Google Scholar 

Download references

Acknowledgments

We would like to thank all of the workers who participated in this study. We also acknowledge the following individuals who contributed to this study: Zahra Afsharinejad for her work on the PON1 genotyping assays; Kelly Fryer-Edwards for her assistance with outreach to study participants; Pam Ernst and Joe Cozzetto from Central Washington Occupational Medicine for their assistance with our recruitment efforts; and Maria Negrete and Pablo Palmandez from the Pacific Northwest Agricultural Safety and Health Center for their assistance with field data collection. Financial support for this project was provided by CDC/NIOSH grants U50OH07544 and T42OH008433, and NIEHS grants P30ES07033, T32ES07262, P42ES04696, and ES009883.

Author information

Authors and Affiliations

  1. Division of Cancer Epidemilogy and Genetics, National Cancer Institute, Bethesda, MD, USA

    Jonathan N. Hofmann

  2. Departments of Environmental & Occupational Health Sciences, University of Washington, Seattle, WA, USA

    Matthew C. Keifer, Federico M. Farin, Richard A. Fenske & Gerald van Belle

  3. Departments of Epidemiology; Departments of Environmental & Occupational Health Sciences, University of Washington, Seattle, WA, USA

    Harvey Checkoway

  4. Departments of Epidemiology, University of Washington, Seattle, USA

    Anneclaire J. De Roos

  5. The Fred Hutchinson Cancer Research Center, Seattle, WA, USA

    Anneclaire J. De Roos

  6. Departments of Medicine (Division of Medical Genetics) and Genome Sciences, University of Washington, Seattle, WA, 98195, USA

    Rebecca J. Richter & Clement E. Furlong

  7. Aberdeen Proving Ground, Aberdeen, MD, USA

    Rebecca J. Richter

  8. Departments of Biostatistics, University of Washington, Seattle, WA, USA

    Gerald van Belle

Authors
  1. Jonathan N. Hofmann
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Matthew C. Keifer
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Harvey Checkoway
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Anneclaire J. De Roos
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Federico M. Farin
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Richard A. Fenske
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. Rebecca J. Richter
    View author publications

    You can also search for this author in PubMed Google Scholar

  8. Gerald van Belle
    View author publications

    You can also search for this author in PubMed Google Scholar

  9. Clement E. Furlong
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Jonathan N. Hofmann .

Editor information

Editors and Affiliations

  1. Division of Cardiology, University of California, Los Angeles, Le Conte Ave. 10833, Los Angeles, 90095-1679, U.S.A.

    Srinivasa T. Reddy

Rights and permissions

Reprints and permissions

Copyright information

© 2010 Humana Press, a part of Springer Science+Business Media, LLC

About this paper

Cite this paper

Hofmann, J.N. et al. (2010). Biomarkers of Sensitivity and Exposure in Washington State Pesticide Handlers. In: Reddy, S. (eds) Paraoxonases in Inflammation, Infection, and Toxicology. Advances in Experimental Medicine and Biology, vol 660. Humana Press. https://doi.org/10.1007/978-1-60761-350-3_3

Download citation

Publish with us

Policies and ethics

Search

Navigation