Effects of occupational exposure to chlorpyrifos on neuropsychological function: a prospective longitudinal study.
BACKGROUND
Exposure to chlorpyrifos (CPF), an organophosphorus (OP) anticholinesterase insecticide, occurs typically in settings where multiple agents are present (e.g., agriculture) and quantitative dose measures may be absent (e.g., pesticide application). Such exposures allow few opportunities to study potential neurobehavioral effects of CPF alone. We studied the relationship between CPF exposure and behavioral function among CPF manufacturing workers, which allowed identification, measurement, and estimation of exposure and important non-exposure variables that potentially could affect study findings.


METHODS
A prospective longitudinal study design was used to compare neurobehavioral function over a one-year period among 53 CPF workers and 60 referent workers. Quantitative and qualitative measures were used, and potential confounders were identified and tested for possible inclusion in our statistical models. Neurobehavioral function was assessed by neuropsychological tests covering various behavioral domains that may be adversely affected by exposure to CPF in sufficient amount.


RESULTS
CPF workers had significantly greater CPF exposures during the study period than did referents at levels where physiologic effects on plasma butyrylcholinesterase (BuChE) activity were apparent and with higher 3,5,6-trichloro-2-pyridinol (TCPy/Cr) urinary excretion (p<0.0001) and lower average BuChE activity (p<0.01). No evidence for impaired neurobehavioral domains by either group of workers was observed at baseline, on repeat examination, or between examinations. CPF workers scored higher than referent workers on the verbal memory domain score (p=0.03) at baseline, but there were no significant changes in verbal memory over time and no significant group-by-time interactions.


CONCLUSIONS
The study provides important information about CPF exposure in the workplace by not supporting our working hypothesis that CPF exposure associated with various aspects of the manufacturing process would be accompanied by adverse neurobehavioral effects detectable by quantitative neurobehavioral testing. Some aspects making this workplace site attractive for study and also present limitations for the generalization of results to other situations that might have exposures that vary widely between and within different facilities and locations. For example, these results might not apply to occupations such as applicators with higher exposure or to workers with low educational levels.
Department of Psychiatry, University of Michigan, USA; Department of Neurology, University of Michigan, USA; Department of Environmental Health Sciences, University of Michigan, USA. Electronic address: sberent@umich.edu.
Stanley
S
Berent
Department of Psychiatry, University of Michigan, USA; Department of Neurology, University of Michigan, USA.
Bruno
B
Giordani
Department of Neurology, University of Michigan, USA; Department of Environmental Health Sciences, University of Michigan, USA.
James W
JW
Albers
Department of Environmental Health Sciences, University of Michigan, USA.
David H
DH
Garabrant
EpidStat Institute, Ann Arbor, MI, USA.
Sarah S
SS
Cohen
Department of Environmental Health Sciences, University of Michigan, USA.
Richard P
RP
Garrison
Department of Neurology, University of Michigan, USA; Department of Environmental Health Sciences, University of Michigan, USA.
Rudy J
RJ
Richardson
D000328:Adult; D001289:Attention Deficit Disorder with Hyperactivity / Q000139:chemically induced*; D016022:Case-Control Studies; D004390:Chlorpyrifos / Q000633:toxicity* / Q000652:urine; D003072:Cognition Disorders / Q000139:chemically induced*; D005260:Female; D006801:Humans; D007221:Industry / Q000706:statistics & numerical data; D007306:Insecticides / Q000633:toxicity* / Q000652:urine; D008137:Longitudinal Studies; D008297:Male; D008569:Memory Disorders / Q000139:chemically induced*; D008875:Middle Aged; D009483:Neuropsychological Tests; D016273:Occupational Exposure; D011597:Psychomotor Performance / Q000187:drug effects; D012044:Regression Analysis; D014706:Verbal Learning / Q000187:drug effects; D014796:Visual Perception / Q000187:drug effects
D007306:Insecticides; D004390:Chlorpyrifos
Chlorpyrifos; Neuropsychology; Neurotoxicity; Occupational exposure; Organophosphates