title: Biomarkers of sensitivity and exposure in Washington state pesticide handlers.
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.
authors.affiliation: Division of Cancer Epidemilogy and Genetics, National Cancer Institute, Bethesda, MD, USA. hofmannjn@mail.nih.gov
authors.forename: Jonathan N
authors.initials: JN
authors.lastname: Hofmann
authors.forename: Matthew C
authors.initials: MC
authors.lastname: Keifer
authors.forename: Harvey
authors.initials: H
authors.lastname: Checkoway
authors.forename: Anneclaire J
authors.initials: AJ
authors.lastname: De Roos
authors.forename: Federico M
authors.initials: FM
authors.lastname: Farin
authors.forename: Richard A
authors.initials: RA
authors.lastname: Fenske
authors.forename: Rebecca J
authors.initials: RJ
authors.lastname: Richter
authors.forename: Gerald
authors.initials: G
authors.lastname: van Belle
authors.forename: Clement E
authors.initials: CE
authors.lastname: Furlong
mesh_terms: D000110:Acetylcholinesterase / Q000378:metabolism*; D043303:Aryldialkylphosphatase / Q000378:metabolism; D015415:Biomarkers / Q000378:metabolism*; D002219:Carbamates / Q000737:chemistry; D006801:Humans; D016273:Occupational Exposure; D009943:Organophosphorus Compounds / Q000009:adverse effects; D010573:Pesticide Residues / Q000009:adverse effects; D010575:Pesticides / Q000009:adverse effects*; D015203:Reproducibility of Results; D012306:Risk; D014861:Washington
chemical_list: D015415:Biomarkers; D002219:Carbamates; D009943:Organophosphorus Compounds; D010573:Pesticide Residues; D010575:Pesticides; C020401:N-methylcarbamate; D000110:Acetylcholinesterase; D043303:Aryldialkylphosphatase