ToxSci Advance Access originally published online on February 25, 2007
Toxicological Sciences 2007 97(1):196-204; doi:10.1093/toxsci/kfm028
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Dose-Effect Analyses of Occupational Chlorpyrifos Exposure and Peripheral Nerve Electrophysiology
* Department of Neurology, University of Michigan Health System, Ann Arbor, Michigan 48109-0032
Department of Environmental Health Sciences, School of Public Health, University of Michigan, Ann Arbor, Michigan 48109-2028
Dow AgroSciences, Indianapolis, Indiana 46268
The Dow Chemical Co., Midland, Michigan 48674
¶ International Epidemiology Institute, Rockville, Maryland 20850
|| Department of Biostatistics, School of Public Health, University of Michigan, Ann Arbor, Michigan 48109-2028
||| Department of Psychiatry (Psychology and Neurobehavioral Toxicology Programs), University of Michigan Health System, Ann Arbor, Michigan 48109
1 To whom correspondence should be addressed at Department of Neurology, 1C325/0032 University Hospital, University of Michigan Health System, 1500 East Medical Center Drive, Ann Arbor, Michigan 48109-0032. Fax: (734) 936-5185. E-mail: jwalbers{at}umich.edu.
Received January 10, 2007; accepted February 17, 2007
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Abstract |
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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 µg/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 µg/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.
Key Words: Chlorpyrifos; insecticides; neurotoxicity; neuropathy; subclinical neuropathy; nerve conduction; peripheral nerve; electrophysiology.