title: Dose-effect analyses of occupational chlorpyrifos exposure and peripheral nerve electrophysiology.
abstract: We performed nerve conduction studies (NCSs) on 113 chemical workers, many of whom had occupational exposure to the organophosphorus insecticide chlorpyrifos (O,O-diethyl-O-[3,5,6-trichloro-2-pyridyl]-phosphorothioate), to identify dose effects of subclinical neuropathy. In this masked longitudinal study, we estimated historic and interim chlorpyrifos exposures and measured excretion of 3,5,6 trichloro-2-pyridinol (TCP), a chlorpyrifos metabolite. TCP excretion among exposed workers suggested an estimated daily chlorpyrifos exposure averaging about 576-627 microg/day and indicated levels approximately 30% (range 0-250%) of the internal dose received by a typical subject exposed during a working day at the threshold limit value of 200 microg/m3. We modeled NCS results using linear mixed models with repeated measures. Although we found no consistent associations between interim chlorpyrifos exposure and NCS results, we identified several significant associations involving historic chlorpyrifos exposure. Most associations, however, reflected effects at low-exposure levels (< 20 mg/m3 x days) without further effects as exposure increased over a 10-fold range (20-220 mg/m3 x days). This suggested small differences among subjects with low or no chlorpyrifos exposure, rather than a dose-related deterioration among subjects with higher exposures. Two NCS results demonstrating apparent subclinical adverse dose effects showed significant but unexplained interaction with education level. The overall results provide little support for the hypothesis that chronic chlorpyrifos exposures at levels in the range associated with appreciable inhibition of B-esterases produce adverse dose effects on peripheral nerve electrophysiology suggestive of subclinical neuropathy.
authors.affiliation: Department of Neurology, University of Michigan Health System, Ann Arbor, Michigan 48109-0032, USA. jwalbers@umich.edu
authors.forename: James W
authors.initials: JW
authors.lastname: Albers
authors.forename: David H
authors.initials: DH
authors.lastname: Garabrant
authors.forename: Joel L
authors.initials: JL
authors.lastname: Mattsson
authors.forename: Carol J
authors.initials: CJ
authors.lastname: Burns
authors.forename: Sarah S
authors.initials: SS
authors.lastname: Cohen
authors.forename: Cami
authors.initials: C
authors.lastname: Sima
authors.forename: Richard P
authors.initials: RP
authors.lastname: Garrison
authors.forename: Rudy J
authors.initials: RJ
authors.lastname: Richardson
authors.forename: Stanley
authors.initials: S
authors.lastname: Berent
mesh_terms: D000200:Action Potentials / Q000187:drug effects; D000328:Adult; D015415:Biomarkers / Q000652:urine; D001711:Biotransformation; D016022:Case-Control Studies; D002617:Chemical Industry; D004390:Chlorpyrifos / Q000378:metabolism / Q000633:toxicity*; D002800:Cholinesterase Inhibitors / Q000378:metabolism / Q000633:toxicity*; D004305:Dose-Response Relationship, Drug; D005260:Female; D006801:Humans; D007306:Insecticides / Q000378:metabolism / Q000633:toxicity*; D016014:Linear Models; D008137:Longitudinal Studies; D008297:Male; D008824:Michigan; D008875:Middle Aged; D009431:Neural Conduction / Q000187:drug effects; D009784:Occupational Diseases / Q000139:chemically induced* / Q000503:physiopathology; D016273:Occupational Exposure; D010525:Peripheral Nerves / Q000187:drug effects* / Q000503:physiopathology; D010523:Peripheral Nervous System Diseases / Q000139:chemically induced* / Q000503:physiopathology; D011446:Prospective Studies; D011728:Pyridones / Q000652:urine; D020711:Threshold Limit Values; D013997:Time Factors
chemical_list: D015415:Biomarkers; D002800:Cholinesterase Inhibitors; D007306:Insecticides; D011728:Pyridones; C012587:3,5,6-trichloro-2-pyridinol; D004390:Chlorpyrifos