The Effects of Occupational Exposure to Chlorpyrifos on the Neurologic Examination of Central Nervous System Function: A Prospective Cohort Study

Abstract

Questions persist about adverse effects such as impaired cognition and attention, incoordination, spasticity, or parkinsonism from chronic, low-level exposures to organophosphate (OP) compounds. In a prospective cohort study, we evaluated chlorpyrifos-manufacturing workers and a referent group on 2 occasions, 1 year apart, to determine whether occupational exposure to chlorpyrifos produced clinically evident central nervous system (CNS) dysfunction. Chlorpyrifos subjects had significantly higher TCP excretion and lower average BuChE activity than referents in a range in which physiological effects on B-esterases exist. Few subjects had neurologic symptoms or signs, and there were no significant group differences in terms of signs at baseline or second examinations. Chronic chlorpyrifos exposure produced no clinical evidence of cortical, pyramidal tract, extrapyramidal, or other CNS dysfunction among chlorpyrifos subjects compared with referents, either at baseline or after 1 year of additional chlorpyrifos exposure.

Paraoxonase status and plasma butyrylcholinesterase activity in chlorpyrifos manufacturing workers

“…We reported earlier that the same chlorpyrifos workers had no measurable adverse neurological symptoms (e.g., numbness, weakness, memory loss) or effects (e.g., neuropathy, mental status change, or nerve conduction abnormalities) attributable to historic or interval chlorpyrifos exposures (Albers et al, 2004a, b). In the present analyses, we found no significant differences in the distribution of PON1 Q192R inferred genotype, alleles, or CPOase activity between the chlorpyrifos manufacturing workers or referents.…”

Cholinesterase inhibition in chlorpyrifos workers: Characterization of biomarkers of exposure and response in relation to urinary TCPy

“…The data regarding ChE activity and urinary TCPy concentration collected as part of a comprehensive longitudinal study of neurological end points in CPF and referent workers and analyzed here present an opportunity to evaluate the exposure-response relationships between ChE activity and urinary TCPy as a marker of exposure to CPF Albers et al, 2004aAlbers et al, , b, c, 2007. No relationship between urinary TCPy and RBC AChE inhibition was observed over the entire range of exposures encountered in this occupationally exposed population, despite the substantial sample size, the collection of repeated measures of AChE activity and urinary TCPy, and the substantial CPF exposures experienced by portions of the study population.…”

“…The study population was previously described in publications by Burns et al (2006) and Albers et al (2004aAlbers et al ( , b, c, 2007. Briefly, the study group consisted of 53 CPF manufacturing workers and a referent group of 60 workers in the Saran manufacturing process with no occupational exposure to organophosphate pesticides or ChE inhibitors (Table 1).…”

“…Urinary TCPy is used to assess exposure to CPF in the population at large (Barr et al, 2005;CDC, 2005) and among applicators and their families (Alexander et al, 2006). Urinary TCPy has been measured in epidemiological studies of children (Berkowitz et al, 2004;Eskenazi et al, 2004Eskenazi et al, , 2007, pesticide applicators (Steenland et al, 2000) and manufacturers (Albers et al, 2004a). None of the studies, however, has analyzed the relationship between urinary TCPy and ChE activity, measurements that represent a range of biomarkers of exposure and effect for CPF.…”

“…A longitudinal study of neurological end points in CPF workers has been previously reported Albers et al, 2004aAlbers et al, , b, c, 2007. In addition to the comprehensive neurological examination components that were the focus of the study, the researchers compiled a unique data set including measures of plasma BuChE and RBC AChE activities and urinary TCPy excretion collected repeatedly over the course of a year in a population with documented occupational exposures and a reference population.…”