← Back to Search
Dose-response And Time-course Of Neurobehavioral Changes Following Oral Chlorpyrifos In Rats Of Different Ages.
Published 2000 · Psychology, Medicine
Save to my Library
Download PDFAnalyze on Scholarcy
Young rats have been shown in several laboratories to be more sensitive to the neurotoxic effects of acute exposure to chlorpyrifos. To examine the neurobehavioral effects of chlorpyrifos as a function of age and dose, we conducted dose-response and time-course assessments in rats of three different ages (postnatal day, or PND, 17, 27, and adults). Doses were selected to span the effective dose range in each age group: PND17 - 4, 10, 20 mg/kg; PND27 - 10, 25, 50 mg/kg; adult - 10, 50, 100 mg/kg. Rats were tested at the time of peak effect on the day of dosing, and again at 1 and 3 days, and at 1 and 2 weeks after a single oral dose. There were age- and sex-related differences in the recovery of these behavioral effects; the adult males recovered from the behavioral effects more quickly than the other age groups, and the adult females showed the slowest recovery (up to at least 3 days). Although these doses had been shown previously to produce a similar degree of cholinesterase inhibition, the neurobehavioral alterations fell into the following three patterns of effect as a function of age. (1) Some endpoints (e.g., gait abnormalities, tremor) showed a dose-response curve that was shifted to the right in the older animals. Calculated ED50 values indicated that the PND17 rats were three- to five-fold more sensitive than the adults. (2) Some measures showed less effect in the youngest rats; for example, maximal motor activity decreases were half as great as with adults. (3) A few effects that were typically observed in adults, e.g., salivation, were not seen at all in the PND17 rats. Thus, differential responses on these neurobehavioral endpoints were observed as a function of age. These data suggest that, for some endpoints, young rats are more sensitive to a range of chlorpyrifos doses; however, the magnitude of age-related differences depends on the specific endpoint and time of assessment, as well as age and sex of the test subject.
This paper references
Pesticides in household dust and soil: exposure pathways for children of agricultural families.
N. Simcox (1995)
Putative M2 muscarinic receptors of rat heart have high affinity for organophosphorus anticholinesterases.
C. L. Silveira (1990)
Single-dose and 13-week repeated-dose neurotoxicity screening studies of chlorpyrifos insecticide.
J. Mattsson (1996)
Age-related differences in sensitivity to organophosphorus pesticides.
C. Pope (1997)
Comparison of the role of esterases in the differential age-related sensitivity to chlorpyrifos and methamidophos.
S. Padilla (2000)
Chronic nicotine treatment delays the developmental increase in brain muscarinic receptors in rat neonate
Jun Zhu (1996)
Chlorpyrifos oxon binds directly to muscarinic receptors and inhibits cAMP accumulation in rat striatum.
R. Huff (1994)
Maturational differences in chlorpyrifos-oxonase activity may contribute to age-related sensitivity to chlorpyrifos.
S. R. Mortensen (1996)
Data Evaluation and Statistical Analysis of Functional Observational Battery Data Using a Linear Models Approach
J. Creason (1989)
Acute and subacute parathion treatment: effects on cholinesterase activities and learning in mice.
L. Reiter (1973)
Toxicity of pesticides in young versus adult rats.
F. Lu (1965)
Studies on factors influencing the acute toxicity of malathion and malaoxon in rats.
J. Brodeur (1967)
Comparative toxicity of some selected pesticides in neonatal and adult rats.
R. Harbison (1975)
Age-related differences in parathion and chlorpyrifos toxicity in male rats: target and nontarget esterase sensitivity and cytochrome P450-mediated metabolism.
T. T. Atterberry (1997)
In vitro effect of chlorpyrifos oxon on muscarinic receptors and adenylate cyclase.
R. Huff (1995)
Esterase activities and soman toxicity in developing rat.
S. Sterri (1985)
Age- and Gender-Related Differences in Sensitivity to Chlorpyrifos in the Rat Reflect Developmental Profiles of Esterase Activities
V. Moser (1998)
Acute behavioral toxicity of carbaryl and propoxur in adults rats
P. Ruppert (1983)
Chemical exposures and animal activity: utility of the figure-eight maze.
Reiter Lw (1983)
Dose-related inhibition of brain and plasma cholinesterase in neonatal and adult rats following sublethal organophosphate exposures.
C. Pope (1992)
Developmental neurotoxicity of chlorpyrifos: cellular mechanisms.
K. Whitney (1995)
Goodman and Gilman's the Pharmacological Basis of Therapeutics
W. Stigelman (1986)
Comparisons of the acute effects of cholinesterase inhibitors using a neurobehavioral screening battery in rats.
V. Moser (1995)
The influence of age on the toxicity and metabolism of methyl parathion and parathion in male and female rats.
G. M. Benke (1975)
Age- and gender-related differences in the time course of behavioral and biochemical effects produced by oral chlorpyrifos in rats.
V. Moser (1998)
Distribution of muscarinic receptor subtypes in rat brain from postnatal to old age.
M. Tice (1996)
Potential chlorpyrifos exposure to residents following standard crack and crevice treatment.
S. L. Byrne (1998)
Exposures from indoor spraying of chlorpyrifos pose greater health risks to children than currently estimated.
D. Davis (1998)
Behavioral Toxicity of Anticholinesterase Agents: Methodological, Neurochemical, and Neuropsychological Aspects
G. Bignami (1975)
Acute toxicity of pesticides in adult and weanling rats.
T. Gaines (1986)
Organophosphorus compounds preferentially affect second messenger systems coupled to M2/M4 receptors in rat frontal cortex
T. Ward (1996)
Effects of Chlorpyrifos on High-Affinity Choline Uptake and [3H]Hemicholinium-3 Binding in Rat Brain
Jing Liu (1996)
Potential exposure and health risks of infants following indoor residential pesticide applications.
R. Fenske (1990)
Chlorpyrifos, parathion, and their oxons bind to and desensitize a nicotinic acetylcholine receptor: relevance to their toxicities.
E. Katz (1997)
The Dose—Response Relation in Pharmacology
R. Tallarida (1979)
Pesticides in the Diets of Infants and Children
Utility of a neurobehavioral screening battery for differentiating the effects of two pyrethroids, permethrin and cypermethrin.
K. L. Mcdaniel (1993)
Correlation of the anticholinesterase activity of a series of organophosphates with their ability to compete with agonist binding to muscarinic receptors.
T. Ward (1993)
Comparison of chlordimeform and carbaryl using a functional observational battery.
V. Moser (1988)
Comparison of Acute Toxicity of Anticholinesterase Insecticides to Weanling and Adult Male Rats.∗
J. Brodeur (1963)
Accumulation of chlorpyrifos on residential surfaces and toys accessible to children.
S. Gurunathan (1998)
Toxicity and effects of malathion on esterases of suckling albino rats.
C. E. Mendoza (1976)
The Relationship of Oral Chlorpyrifos Effects on Behavior, Cholinesterase Inhibition, and Muscarinic Receptor Density in Rat
A. C. Nostrandt (1997)
Comparison of in vivo cholinesterase inhibition in neonatal and adult rats by three organophosphorothioate insecticides.
C. Pope (1991)
This paper is referenced by
Behavioral Toxicity of Cholinesterase Inhibitors
P. Bushnell (2006)
Pre-natal/juvenile chlorpyrifos exposure associated with immunotoxicity in adulthood in Swiss albino mice
A. Singh (2013)
Pharmacokinetics and pharmacodynamics of chlorpyrifos in adult male Long-Evans rats following repeated subcutaneous exposure to chlorpyrifos.
C. Ellison (2011)
The effect of chlorpyrifos and chlorpyrifos-oxon on brain cholinesterase, muscarinic receptor binding, and neurotrophin levels in rats following early postnatal exposure.
Angela M Betancourt (2004)
In vitro inhibition of plasma and brain cholinesterases of growing chicks by chlorpyrifos and dichlorvos
F. Mohammad (2014)
Characterization of chlorpyrifos-induced apoptosis in placental cells.
Marilyn D. Saulsbury (2008)
A mechanistic approach for modulation of chlorpyrifos-induced toxicity in human lymphocytes by melatonin, coenzyme Q10, and vinpocetine
F. Ghayomi (2016)
Postnatal chlorpyrifos exposure and apolipoprotein E (APOE) genotype differentially affect cholinergic expression and developmental parameters in transgenic mice.
Pia Basaure (2018)
Carnosic Acid Affords Mitochondrial Protection in Chlorpyrifos-Treated Sh-Sy5y Cells
M. R. de Oliveira (2016)
Cholinesterase inhibition and toxicokinetics in immature and adult rats after acute or repeated exposures to chlorpyrifos or chlorpyrifos-oxon.
M. S. Marty (2012)
Developmental neurotoxicity elicited by prenatal or postnatal chlorpyrifos exposure: effects on neurospecific proteins indicate changing vulnerabilities.
S. Garcia (2003)
Molecular and Biochemical Evidences for Beneficial Effects of Zinc Oxide Nanoparticles in Modulation of Chlorpyrifos Toxicity in Human Lymphocytes
M. Navaei‐Nigjeh (2018)
Molecular detection of M. tuberculosis and M. bovis and hematological and biochemical analyses in agricultural sprayers exposed to pesticides: A cross-sectional study in Punjab, Pakistan during 2014–2016
S. Riaz (2017)
Epidemiological studies of pesticide- exposed individuals and their clinical implications
K. Jamil (2007)
Immunological Abnormalities in Humans Chronically Exposed to Chlorpyrifos
J. D. Thrasher (2002)
Prenatal chlorpyrifos exposure in rats causes persistent behavioral alterations.
E. Levin (2002)
Toxicopathological Effects of Concurrent Feeding of Organophosphate and Arsenic and its Attenuation with Polyphenolic Grape Seed Extract in Broiler Chicks
M. Ahmad (2014)
Impairment of novel object recognition in adulthood after neonatal exposure to diazinon
Tin-Tin Win-Shwe (2012)
Time-course, dose-response, and age comparative sensitivity of N-methyl carbamates in rats.
V. Moser (2010)
Potential pharmacological strategies for the improved treatment of organophosphate-induced neurotoxicity.
Shamsherjit Kaur (2014)
Age dependence of organophosphate and carbamate neurotoxicity in the postnatal rat: extrapolation to the human.
Charles A Vidair (2004)
Studying the Relation Between Pesticide Exposure and Human Development
R. Whyatt (2006)
Potential developmental neurotoxicity of pesticides used in Europe
M. Bjørling-Poulsen (2008)
Morphologic effects of subtoxic neonatal chlorpyrifos exposure in developing rat brain: regionally selective alterations in neurons and glia.
T. Roy (2004)
Induction of reproductive deficits in nematode Caenorhabditis elegans exposed to metals at different developmental stages.
Yuling Guo (2009)
Sub-lethal Effects of Chlorpyrifos on Big Brown Bats (Eptesicus fuscus)
Ronny R. Eidels (2016)
Cadmium and chlorpyrifos inhibit cellular immune response in spleen of rats
P. Wang (2017)
Age-Related Differences in Acetylcholinesterase Inhibition Produced by Organophosphorus and N-Methyl Carbamate Pesticides
V. Moser (2011)
Effect of diplodiatoxin (Stenocarpella maydis) on some enzymatic profiles in male and female rats.
M. F. Rahman (2002)
Impaired retention in AβPP Swedish mice six months after oral exposure to chlorpyrifos.
F. Peris-Sampedro (2014)
Dynamin-related protein 1 mediates mitochondria-dependent apoptosis in chlorpyrifos-treated SH-SY5Y cells.
J. H. Park (2015)
Transmissible spongiform encephalopathies: a family of etiologically complex diseases--a review.
M. Bounias (2002)See more