Review of the toxicology of chlorpyrifos with an emphasis on human exposure and neurodevelopment

David L. Eaton, Robert B. Daroff, Herman Autrup, James Bridges, Patricia Buffler, Lucio G. Costa, Joseph Coyle, Guy McKhann, William C. Mobley, Lynn Nadel, Diether Neubert, Rolf Schulte-Hermann, Peter Spencer

Research output: Contribution to journalArticle

301 Citations (Scopus)

Abstract

This review examines the large body of toxicological and epidemiological information on human exposures to chlorpyrifos, with an emphasis on the controversial potential for chlorpyrifos to induce neurodevelopmental effects at low doses. The results of this review demonstrate that the use of urinary 3,5,6-trichlorpyridinol (TCPy), a metabolite of chlorpyrifos as a biomarker of nonoccupational exposure is problematic and may overestimate nonoccupational exposures to chlorpyrifos by 10-to 20-fold because of the widespread presence of both TCPy and chlorpyrifos-methyl in the food supply. Current "background" (nonoccupational) levels of exposure to chlorpyrifos are several orders of magnitude lower than those required to inhibit plasma cholinesterase activity, which is a more sensitive target than nervous system cholinesterase. However, several in vitro studies have identified putative neurodevelopmental mechanisms that are altered at concentrations of chlorpyrifos below those that inhibit cholinesterases. Although one human cohort study reported an association between maternal and cord blood chlorpyrifos levels and several measures of neurodevelopment, two other cohort studies that utilized urinary TCPy as a surrogate for chlorpyrifos exposure did not demonstrate an association. Although the weight of the scientific evidence demonstrates that current levels of chlorpyrifos exposure will not have any adverse effects on neurodevelopment that might result from inhibition of nervous system cholinesterases, several recent studies propose alternative mechanisms. Thus, further in vivo investigation on neurodevelopment in an appropriate animal model is needed; additional epidemiological studies may be warranted if a suitable, chlorpyrifos-exposed cohort can be identified and more rigorous measures of exposure are utilized.

Original languageEnglish (US)
Pages (from-to)1-125
Number of pages125
JournalCritical Reviews in Toxicology
Volume38
Issue numberSUPPL.2
DOIs
StatePublished - Sep 2008

Fingerprint

Chlorpyrifos
Toxicology
Cholinesterases
Neurology
Nervous System
Cohort Studies
Association reactions
Food supply
Food Supply
Biomarkers
Metabolites
Fetal Blood
Epidemiologic Studies
Animals
Blood
Animal Models
Mothers

Keywords

  • Chlorpyrifos
  • Cholinesterase inhibition
  • Epidemiology
  • Mechanism
  • Neurobehavior
  • Neurodevelopment
  • Organophosphorous insecticide
  • Review
  • Toxicology
  • Trichloropyridinol

ASJC Scopus subject areas

  • Toxicology

Cite this

Review of the toxicology of chlorpyrifos with an emphasis on human exposure and neurodevelopment. / Eaton, David L.; Daroff, Robert B.; Autrup, Herman; Bridges, James; Buffler, Patricia; Costa, Lucio G.; Coyle, Joseph; McKhann, Guy; Mobley, William C.; Nadel, Lynn; Neubert, Diether; Schulte-Hermann, Rolf; Spencer, Peter.

In: Critical Reviews in Toxicology, Vol. 38, No. SUPPL.2, 09.2008, p. 1-125.

Research output: Contribution to journalArticle

Eaton, DL, Daroff, RB, Autrup, H, Bridges, J, Buffler, P, Costa, LG, Coyle, J, McKhann, G, Mobley, WC, Nadel, L, Neubert, D, Schulte-Hermann, R & Spencer, P 2008, 'Review of the toxicology of chlorpyrifos with an emphasis on human exposure and neurodevelopment', Critical Reviews in Toxicology, vol. 38, no. SUPPL.2, pp. 1-125. https://doi.org/10.1080/10408440802272158
Eaton, David L. ; Daroff, Robert B. ; Autrup, Herman ; Bridges, James ; Buffler, Patricia ; Costa, Lucio G. ; Coyle, Joseph ; McKhann, Guy ; Mobley, William C. ; Nadel, Lynn ; Neubert, Diether ; Schulte-Hermann, Rolf ; Spencer, Peter. / Review of the toxicology of chlorpyrifos with an emphasis on human exposure and neurodevelopment. In: Critical Reviews in Toxicology. 2008 ; Vol. 38, No. SUPPL.2. pp. 1-125.
@article{323ec57e386e482b8ea86bc2c4eea590,
title = "Review of the toxicology of chlorpyrifos with an emphasis on human exposure and neurodevelopment",
abstract = "This review examines the large body of toxicological and epidemiological information on human exposures to chlorpyrifos, with an emphasis on the controversial potential for chlorpyrifos to induce neurodevelopmental effects at low doses. The results of this review demonstrate that the use of urinary 3,5,6-trichlorpyridinol (TCPy), a metabolite of chlorpyrifos as a biomarker of nonoccupational exposure is problematic and may overestimate nonoccupational exposures to chlorpyrifos by 10-to 20-fold because of the widespread presence of both TCPy and chlorpyrifos-methyl in the food supply. Current {"}background{"} (nonoccupational) levels of exposure to chlorpyrifos are several orders of magnitude lower than those required to inhibit plasma cholinesterase activity, which is a more sensitive target than nervous system cholinesterase. However, several in vitro studies have identified putative neurodevelopmental mechanisms that are altered at concentrations of chlorpyrifos below those that inhibit cholinesterases. Although one human cohort study reported an association between maternal and cord blood chlorpyrifos levels and several measures of neurodevelopment, two other cohort studies that utilized urinary TCPy as a surrogate for chlorpyrifos exposure did not demonstrate an association. Although the weight of the scientific evidence demonstrates that current levels of chlorpyrifos exposure will not have any adverse effects on neurodevelopment that might result from inhibition of nervous system cholinesterases, several recent studies propose alternative mechanisms. Thus, further in vivo investigation on neurodevelopment in an appropriate animal model is needed; additional epidemiological studies may be warranted if a suitable, chlorpyrifos-exposed cohort can be identified and more rigorous measures of exposure are utilized.",
keywords = "Chlorpyrifos, Cholinesterase inhibition, Epidemiology, Mechanism, Neurobehavior, Neurodevelopment, Organophosphorous insecticide, Review, Toxicology, Trichloropyridinol",
author = "Eaton, {David L.} and Daroff, {Robert B.} and Herman Autrup and James Bridges and Patricia Buffler and Costa, {Lucio G.} and Joseph Coyle and Guy McKhann and Mobley, {William C.} and Lynn Nadel and Diether Neubert and Rolf Schulte-Hermann and Peter Spencer",
year = "2008",
month = "9",
doi = "10.1080/10408440802272158",
language = "English (US)",
volume = "38",
pages = "1--125",
journal = "Critical Reviews in Toxicology",
issn = "1040-8444",
publisher = "Informa Healthcare",
number = "SUPPL.2",

}

TY - JOUR

T1 - Review of the toxicology of chlorpyrifos with an emphasis on human exposure and neurodevelopment

AU - Eaton, David L.

AU - Daroff, Robert B.

AU - Autrup, Herman

AU - Bridges, James

AU - Buffler, Patricia

AU - Costa, Lucio G.

AU - Coyle, Joseph

AU - McKhann, Guy

AU - Mobley, William C.

AU - Nadel, Lynn

AU - Neubert, Diether

AU - Schulte-Hermann, Rolf

AU - Spencer, Peter

PY - 2008/9

Y1 - 2008/9

N2 - This review examines the large body of toxicological and epidemiological information on human exposures to chlorpyrifos, with an emphasis on the controversial potential for chlorpyrifos to induce neurodevelopmental effects at low doses. The results of this review demonstrate that the use of urinary 3,5,6-trichlorpyridinol (TCPy), a metabolite of chlorpyrifos as a biomarker of nonoccupational exposure is problematic and may overestimate nonoccupational exposures to chlorpyrifos by 10-to 20-fold because of the widespread presence of both TCPy and chlorpyrifos-methyl in the food supply. Current "background" (nonoccupational) levels of exposure to chlorpyrifos are several orders of magnitude lower than those required to inhibit plasma cholinesterase activity, which is a more sensitive target than nervous system cholinesterase. However, several in vitro studies have identified putative neurodevelopmental mechanisms that are altered at concentrations of chlorpyrifos below those that inhibit cholinesterases. Although one human cohort study reported an association between maternal and cord blood chlorpyrifos levels and several measures of neurodevelopment, two other cohort studies that utilized urinary TCPy as a surrogate for chlorpyrifos exposure did not demonstrate an association. Although the weight of the scientific evidence demonstrates that current levels of chlorpyrifos exposure will not have any adverse effects on neurodevelopment that might result from inhibition of nervous system cholinesterases, several recent studies propose alternative mechanisms. Thus, further in vivo investigation on neurodevelopment in an appropriate animal model is needed; additional epidemiological studies may be warranted if a suitable, chlorpyrifos-exposed cohort can be identified and more rigorous measures of exposure are utilized.

AB - This review examines the large body of toxicological and epidemiological information on human exposures to chlorpyrifos, with an emphasis on the controversial potential for chlorpyrifos to induce neurodevelopmental effects at low doses. The results of this review demonstrate that the use of urinary 3,5,6-trichlorpyridinol (TCPy), a metabolite of chlorpyrifos as a biomarker of nonoccupational exposure is problematic and may overestimate nonoccupational exposures to chlorpyrifos by 10-to 20-fold because of the widespread presence of both TCPy and chlorpyrifos-methyl in the food supply. Current "background" (nonoccupational) levels of exposure to chlorpyrifos are several orders of magnitude lower than those required to inhibit plasma cholinesterase activity, which is a more sensitive target than nervous system cholinesterase. However, several in vitro studies have identified putative neurodevelopmental mechanisms that are altered at concentrations of chlorpyrifos below those that inhibit cholinesterases. Although one human cohort study reported an association between maternal and cord blood chlorpyrifos levels and several measures of neurodevelopment, two other cohort studies that utilized urinary TCPy as a surrogate for chlorpyrifos exposure did not demonstrate an association. Although the weight of the scientific evidence demonstrates that current levels of chlorpyrifos exposure will not have any adverse effects on neurodevelopment that might result from inhibition of nervous system cholinesterases, several recent studies propose alternative mechanisms. Thus, further in vivo investigation on neurodevelopment in an appropriate animal model is needed; additional epidemiological studies may be warranted if a suitable, chlorpyrifos-exposed cohort can be identified and more rigorous measures of exposure are utilized.

KW - Chlorpyrifos

KW - Cholinesterase inhibition

KW - Epidemiology

KW - Mechanism

KW - Neurobehavior

KW - Neurodevelopment

KW - Organophosphorous insecticide

KW - Review

KW - Toxicology

KW - Trichloropyridinol

UR - http://www.scopus.com/inward/record.url?scp=51049112666&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=51049112666&partnerID=8YFLogxK

U2 - 10.1080/10408440802272158

DO - 10.1080/10408440802272158

M3 - Article

VL - 38

SP - 1

EP - 125

JO - Critical Reviews in Toxicology

JF - Critical Reviews in Toxicology

SN - 1040-8444

IS - SUPPL.2

ER -