Serum cholinesterase inhibition in relation to paraoxonase-1 (PON1) status among organophosphate-exposed agricultural pesticide handlers.
BACKGROUND
Animal studies have demonstrated that low paraoxonase-1 (PON1) status (i.e., low catalytic efficiency and/or low plasma PON1 activity) is associated with neurotoxic effects after exposure to several organophosphate (OP) insecticides. However, few human studies have investigated associations between PON1 status and intermediate end points, such as serum cholinesterase [butyrylcholinesterase (BuChE)] inhibition, among OP-exposed individuals.


OBJECTIVE
We evaluated the relation between plasma PON1 status and BuChE inhibition among OP-exposed agricultural pesticide handlers.


METHODS
Agricultural pesticide handlers in Washington State were recruited during the 2006 and 2007 spray seasons when they were seen for follow-up ChE testing by collaborating medical providers as part of a statewide monitoring program. Blood samples were collected from 163 participants and tested for PON1 status based on plasma PON1 activity [arylesterase (AREase)] and PON1 Q192R genotype. We evaluated percent change in BuChE activity from baseline level in relation to PON1 status.


RESULTS
We observed significantly greater BuChE inhibition among QQ homozygotes relative to RR homozygotes (p = 0.036). Lower levels of plasma PON1 activity were significantly associated with greater BuChE inhibition (p = 0.004). These associations remained after adjustment for year, days since baseline test, age, and OP exposure in the last 30 days.


CONCLUSIONS
We found that both low PON1 catalytic efficiency (i.e., the Q192 alloform) and low plasma PON1 activity were associated with BuChE inhibition among OP-exposed agricultural pesticide handlers. Corroborative findings from future studies with prospective collection of blood samples for PON1 testing, more sensitive markers of OP-related effects, and larger sample sizes are needed.
Hofmann
Jonathan N
JN
Department of Epidemiology, University of Washington, Seattle, Washington, USA. hofmannjn@mail.nih.gov
Keifer
Matthew C
MC
Furlong
Clement E
CE
De Roos
Anneclaire J
AJ
Farin
Federico M
FM
Fenske
Richard A
RA
van Belle
Gerald
G
Checkoway
Harvey
H
D000293:Adolescent; D000328:Adult; D000383:Agriculture; D043303:Aryldialkylphosphatase / Q000097:blood*; D002091:Butyrylcholinesterase / Q000097:blood* / Q000187:drug effects; D002800:Cholinesterase Inhibitors / Q000494:pharmacology*; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D016273:Occupational Exposure; D014861:Washington; D055815:Young Adult
D002800:Cholinesterase Inhibitors; D002091:Butyrylcholinesterase; D043303:Aryldialkylphosphatase; C468406:PON1 protein, human