Chlorpyrifos (Dursban)

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Summary

TBD.

Studies and Reports

• Albers J et al., Dose-effect analyses of occupational chlorpyrifos exposure and peripheral nerve electrophysiology, Toxicol Sci. 2007 May;97(1):196-204. Epub 2007 Feb 25.
  • 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."
• Solomon K et al., Nonagricultural and residential exposures to pesticides, Scand J Work Environ Health. 2005;31 Suppl 1:74-81; discussion 63-5.
  • Abstract. "Epidemiologic studies and risk assessments conducted to assess the chronic effects of pesticides are limited by inadequate measurements of pesticide exposures, and surrogates for these data are frequently used. In this paper, pesticide use and absorbed dose previously measured in residential and occupational settings are used to evaluate the hypothesis that there is a relationship between pesticide use and exposure. For homeowner applicators of 2,4-dichlorophenoxyacetic acid (2,4-D) and chlorpyrifos, exposures were poorly correlated with the amount of herbicide used (r2 = 0.01 to 0.40); however, exposures from a granular product were consistently less than those with liquid formulation. For professional landscape applicators, exposure over 14 days and 7 days of use was poorly correlated with the amount of 2,4-D sprayed (r2 = 0.17 and 0.21, respectively). However, inclusion of the type of spray nozzle used and the use of gloves while spraying in the model explained increased predictability and explained 68% of the variation."
• Albers J et al., Absence of sensory neuropathy among workers with occupational exposure to chlorpyrifos, Muscle Nerve. 2004 May;29(5):677-86.
  • Abstract. "Several studies have reported the occurrence of sensory neuropathy with exposure to chlorpyrifos and other organophosphorus insecticides, at levels not associated with overt toxicity. We evaluated 113 chemical workers, including 53 of 66 (80%) eligible chlorpyrifos workers and 60 of 74 (81%) randomly selected referent workers, to identify evidence of sensory neuropathy or subclinical neuropathy. Compared to referents, chlorpyrifos subjects had significantly longer duration of work in chlorpyrifos-exposed areas (9.72 vs. 0.01 years; P < 0.0001), greater cumulative chlorpyrifos exposure (64.16 vs. 0.69 mg/m(3). day; P < 0.0001), higher urine 3,5,6-trichloro-2-pyridinol (TCP) excretion (108.6 vs. 4.3 microg/g creatinine; P < 0.0001), and lower plasma butyrylcholinesterase (BuChE) activity (7281 vs. 8176 mU/ml; P = 0.003). Despite exposures among chlorpyrifos subjects to levels at which well-described physiological effects on B-esterases exist, the frequency of symptoms or signs of neuropathy did not differ significantly between groups, and the only 2 subjects fulfilling criteria for confirmed neuropathy were both in the referent group. Mean nerve conduction study results were comparable to established control values and did not differ significantly between groups. We found no evidence of sensory neuropathy or isolated peripheral abnormalities among subjects with long-term chlorpyrifos exposure at levels known to be associated with the manufacturing process."
• Albers J et al, The effects of occupational exposure to chlorpyrifos on the neurologic examination of central nervous system function: a prospective cohort study, J Occup Environ Med. 2004 Apr;46(4):367-78.
  • 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."
• Albers J et al., The effects of occupational exposure to chlorpyrifos on the peripheral nervous system: a prospective cohort study, Occup Environ Med. 2004 Mar;61(3):201-11.
  • Conclusions. "Chronic chlorpyrifos exposure during the manufacturing process sufficient to produce biological effects on BuChE activity was not associated with clinically evident or subclinical peripheral neuropathy at baseline or with measurable deterioration among chlorpyrifos subjects compared to referents after one year of additional exposure."
• Albers J et al., Analysis of chlorpyrifos exposure and human health: expert panel report, J Toxicol Environ Health B Crit Rev. 1999 Oct-Dec;2(4):301-24.
  • Abstract. "This report summarizes the deliberations of an eight-member panel of scientists convened by Dow AgroSciences in cooperation with the U.S. Environmental Protection Agency (EPA). The panel was charged with evaluating the scientific literature on the health effects potentially associated with exposure to the insecticide chlorpyrifos. Specifically, the panel was asked to (1) evaluate human experience data available and address the adequacy of the available current literature; (2) develop a list of recommendations for epidemiology studies, including appropriate endpoints and study populations, and strengths and weaknesses of each approach; and (3) draft a report to summarize its recommendations. The panel assessed the quality of the existing epidemiologic literature on chlorpyrifos and specific outcomes such as neuropathy (including organophosphate induced delayed neurotoxicity), behavior (cognition and affect), immunologic, and multiple complaints (also referred to as multiple chemical sensitivities). The majority of panel members (five members) agreed that the literature reviewed provided little or no scientific evidence that chlorpyrifos exposure causes harm to human health other than its known cholinergic effects associated with acute poisoning. Those panel members voting in the minority (three members) agreed that the studies reviewed provided inadequate evidence to preclude the possibility of adverse effects to human health from chlorpyrifos exposure at levels associated with its manufacture or professional application. Those voting in the minority suggested further investigation of cohort(s) of workers engaged in either the manufacture or the professional application of chlorpyrifos, or both. Compared to the general population, these groups have relatively high levels of exposure to chlorpyrifos. The primary health outcomes recommended for study were cognitive and affective disorders, with consideration of the assessment of peripheral neuropathy also suggested for at least a subset of the cohort."
• Shurdut B et al., Aggregate Exposures under the Food Quality Protection Act: An Approach Using Chlorpyrifos, Regulatory Toxicology and Pharmacology (28:2;165-177), October 1998.
  • Abstract. "The Food Quality Protection Act of 1996 (Public Law 104-170, August 3, 1996), which amended the Federal Insecticide, Fungicide, and Rodenticide Act (FIFRA) and the Federal Food, Drug, and Cosmetic Act (FFDCA), requires that the EPA evaluate pesticide safety in light of potential aggregate exposures from both nondietary and dietary routes. As with any new legislation, there has been considerable discussion and challenges presented within the regulatory and scientific communities regarding the effective implementation of this act as it relates to the determination of aggregate exposures. This paper describes a novel methodology incorporating personal exposure factors, route-specific exposure measurements, and usage information to characterize potential aggregate exposures to a widely used pesticide, chlorpyrifos. A calendar model framework has been developed to describe potential multipathway exposures to individuals. The model assimilates information regarding the typical use patterns of chlorpyrifos-containing pesticides in concert with quantitative exposure and dose measurements to estimate the probability and magnitude of exposures to members of the U.S. population. Studies measuring 3,5,6-trichloropyridinol, the primary metabolite of chlorpyrifos, in the urine of individuals within the United States show that aggregate exposures derived from this approach are consistent with actual population-based exposures to chlorpyrifos. According to this assessment, potential health risks attributed to exposure to chlorpyrifos are low when compared to relevant toxicological end points."
• Burns C et al., Update of the morbidity experience of employees potentially exposed to chlorpyrifos, Occup Environ Med. 1998 Jan;55(1):65-70.
  • Conclusion. "These data do not support a cause and effect relation of the diagnoses mentioned and exposure to chlorpyrifos.

Additional Resources

• Fumento M, Let Us Spray, Forbes, August 21, 2000.