Exposures from Indoor Spraying of Chlorpyrifos Pose Greater Health Risks to Children than Currently Estimated

Davis, Devra Lee; Ahmed, A. Karim

doi:10.2307/3434033

Cited by 11 publications

(10 citation statements)

References 13 publications

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“…There is increasing public and regulatory concern that exposure to low levels of organophosphorus pesticides (OPs) may interfere with neurodevelopment in children (Costa, 2006). This concern was initially triggered by animal studies demonstrating that the developing nervous system is more susceptible than the mature nervous system to the neurotoxic effects of OPs (Pope et al, 1991;Pope and Chakraborti, 1992;Mortensen et al, 1998;, and by documentation of widespread exposure of children to OPs in both rural and urban environments (Davis and Ahmed, 1998;Eskenazi et al, 1999;Landrigan et al, 1999;Adgate et al, 2001;Lu et al, 2001;Whyatt and Barr, 2001;CDC, 2003;Curl et al, 2003;Barr et al, 2004). Recent epidemiological studies indicating a link between exposure to low levels of OPs and neurobehavioral deficits in infants (Engel et al, 2007) and children (Rohlman et al, 2005;Kofman et al, 2006;Eskenazi et al, 2007;Lizardi et al, 2007) further heighten this concern, and underscore the need to better understand the cellular and molecular mechanism(s) of OP developmental neurotoxicity (Costa, 2006).…”

Section: Introductionmentioning

confidence: 99%

Chlorpyrifos and chlorpyrifos-oxon inhibit axonal growth by interfering with the morphogenic activity of acetylcholinesterase

Yang

Howard

Bruun

et al. 2008

Toxicology and Applied Pharmacology

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A primary role of acetylcholinesterase (AChE) is regulation of cholinergic neurotransmission by hydrolysis of synaptic acetylcholine. In the developing nervous system, however, AChE also functions as a morphogenic factor to promote axonal growth. This raises the question of whether organophosphorus pesticides (OPs) that are known to selectively bind to and inactivate the enzymatic function of AChE also interfere with its morphogenic function to perturb axonogenesis. To test this hypothesis, we exposed primary cultures of sensory neurons derived from embryonic rat dorsal root ganglia (DRG) to chlorpyrifos (CPF) or its oxon metabolite (CPFO). Both OPs significantly decreased axonal length at concentrations that had no effect on cell viability, protein synthesis or the enzymatic activity of AChE. Comparative analyses of the effects of CPF and CPFO on axonal growth in DRG neurons cultured from AChE nullizygous (AChE -/-) versus wild type (AChE +/+) mice indicated that while these OPs inhibited axonal growth in AChE+/+ DRG neurons, they had no effect on axonal growth in AChE -/- DRG neurons. However, transfection of AChE -/- DRG neurons with cDNA encoding full-length AChE restored the wild type response to the axon inhibitory effects of OPs. These data indicate that inhibition of axonal growth by OPs requires AChE, but the mechanism involves inhibition of the morphogenic rather than enzymatic activity of AChE. These findings suggest a novel mechanism for explaining not only the functional deficits observed in children and animals following developmental exposure to OPs, but also the increased vulnerability of the developing nervous system to OPs.

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Section: Introductionmentioning

confidence: 99%

Chlorpyrifos and chlorpyrifos-oxon inhibit axonal growth by interfering with the morphogenic activity of acetylcholinesterase

Yang

Howard

Bruun

et al. 2008

Toxicology and Applied Pharmacology

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“…If exposure is less than that needed to cause significant cholinesterase depression, then no signs or symptoms related to chlorpyrifos exposure occur. However, recently Davis and Ahmed [8] suggested that exposure from indoor spraying of chlorpyrifos poses greater health risks than previously estimated. Therefore, chlorpyrifos has long been regarded as a relatively safe pesticide for household use [7].…”

Section: Chlorpyrifos (Oo-diethyl O-mentioning

confidence: 94%

“…According to the U.S. EPA, 972 registered products contain chlorpyrifos, including widespread uses for termite and roach control [8]. It is estimated that chlorpyrifos is used in more than 20 million American homes each year to protect humans and pets from the harmful effects of insect pests (e.g., termites, ticks, cockroaches, fire ants).…”

Section: Environmental Implicationsmentioning

confidence: 99%

“…It is estimated that chlorpyrifos is used in more than 20 million American homes each year to protect humans and pets from the harmful effects of insect pests (e.g., termites, ticks, cockroaches, fire ants). According to the U.S. EPA, 972 registered products contain chlorpyrifos, including widespread uses for termite and roach control [8].…”

Section: Environmental Implicationsmentioning

confidence: 99%

“…Therefore, chlorpyrifos has long been regarded as a relatively safe pesticide for household use [7]. However, recently Davis and Ahmed [8] suggested that exposure from indoor spraying of chlorpyrifos poses greater health risks than previously estimated. In addition, Slokin [9] found evidence that exposure to low doses of chlorpyrifos can adversely affect cell replication and differentiation processes * To whom correspondence may be addressed (laird@nstl.gov).…”

Section: Introductionmentioning

confidence: 99%

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Abiotic Transformation of Chlorpyrifos to Chlorpyrifos Oxon in Chlorinated Water

Wu¹,

Laird²

2003

Environ Toxicol Chem

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In vivo transformation of chlorpyrifos to chlorpyrifos oxon is believed to be a prerequisite for this insecticide to display acute toxicity to organisms. We discovered that active chlorine dispersed in water causes the rapid abiotic transformation of chlorpyrifos to chlorpyrifos oxon. The proposed mechanism for the transformation is an electrophilic attack by hypochlorous acid (HOCl) on the thion (P=S) double bond of chlorpyrifos followed by desulfuration of chlorpyrifos to its oxon analog. The pH of a Cl-aqueous solution controls the speciation of HOCl and hypochlorite (OCl-) in water and thereby influences the transformation process. Chlorpyrifos oxon is a potent anticholinesterase that is about 1,000 times more toxic than chlorpyrifos. Because chlorination is commonly used for treatment of domestic water supplies, the findings raise a new concern about the safety of domestic use of chlorpyrifos products.

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Chlorpyrifos‐induced DNA damage in rat liver and brain

Mehta

Verma

Srivastava

2008

Environ and Mol Mutagen

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Chlorpyrifos (O,O'-diethyl-O-3,5,6-trichloro-2-pyridyl phosphorothionate, CPF) is a broad spectrum organophosphate pesticide used to control a variety of pests. The present study was undertaken to test the in vivo genotoxic potential of CPF in rats, using the single cell gel electrophoresis (or comet) assay. The rats were administered 50 mg and 100 mg CPF/kg body weight daily for 1, 2, and 3 days as well as 1.12 mg and 2.24 mg CPF/kg body weight for 90 days. The level of DNA damage was estimated by scoring 100 cells per animal, dividing into five types: types 0, I, II, III, and IV. The results clearly indicate that exposure to CPF, acutely or chronically, caused a dose-dependent increase in DNA damage in the liver and brain of rats. From the present study, it can be concluded that CPF exhibits genotoxic potential in vivo.

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Exposures from Indoor Spraying of Chlorpyrifos Pose Greater Health Risks to Children than Currently Estimated

Cited by 11 publications

References 13 publications

Chlorpyrifos and chlorpyrifos-oxon inhibit axonal growth by interfering with the morphogenic activity of acetylcholinesterase

Chlorpyrifos and chlorpyrifos-oxon inhibit axonal growth by interfering with the morphogenic activity of acetylcholinesterase

Abiotic Transformation of Chlorpyrifos to Chlorpyrifos Oxon in Chlorinated Water

Chlorpyrifos‐induced DNA damage in rat liver and brain

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