Environmentally relevant mixtures in cumulative assessments: An acute study of toxicokinetics and effects on motor activity in rats exposed to a mixture of pyrethroids

Autores
Starr, James M.; Scollon, Edward J.; Hughes, Michael F.; Ross, David G.; Graham, Stephen E.; Crofton, Kevin M.; Wolansky, Marcelo Javier; DeVito, Michael J.; Tornero-Velez, Rogelio
Año de publicación
2012
Idioma
inglés
Tipo de recurso
artículo
Estado
versión publicada
Descripción
Due to extensive use, human exposure to multiple pyrethroid insecticides occurs frequently. Studies of pyrethroid neurotoxicity suggest a common mode of toxicity and that pyrethroids should be considered cumulatively to model risk. The objective of this work was to use a pyrethroid mixture that reflects human exposure to common pyrethroids to develop comparative toxicokinetic profiles in rats, and then model the relationship between brain concentration and motor activity. Data from a national survey of child care centers were used to make a mixture reflecting proportions of the most prevalent pyrethroids: permethrin, cypermethrin, β-cyfluthrin, deltamethrin, and esfenvalerate. The mixture was administered orally at one of two concentrations (11.2 and 27.4 mg/kg) to adult male rats. At intervals from 1 to 24h, motor activity was assessed and the animals were sacrificed. Pyrethroid concentrations were measured in the blood, liver, fat, and brain. After controlling for dose, there were no differences in any tissue concentrations, except blood at the initial time point. Elimination half-lives for all pyrethroids in all tissues were < 7h. Brain concentrations of all pyrethroids (when cis- and trans-permethrin were pooled) at the initial time point were proportional to their relative doses. Decreases in motor activity indicated dose additivity, and the relationship between pyrethroid brain concentration and motor activity was described by a four-parameter sigmoidal Emax model. This study links environmental data with toxicokinetic and neurobehavioral assays to support cumulative risk assessments of pyrethroid pesticides. The results support the additive model of pyrethroid effect on motor activity and suggest that variation in the neurotoxicity of individual pyrethroids is related to toxicodynamic rather than toxicokinetic differences.
Fil: Starr, James M.. United States Environmental Protection Agency; Estados Unidos
Fil: Scollon, Edward J.. United States Environmental Protection Agency; Estados Unidos
Fil: Hughes, Michael F.. United States Environmental Protection Agency; Estados Unidos
Fil: Ross, David G.. United States Environmental Protection Agency; Estados Unidos
Fil: Graham, Stephen E.. United States Environmental Protection Agency; Estados Unidos
Fil: Crofton, Kevin M.. United States Environmental Protection Agency; Estados Unidos
Fil: Wolansky, Marcelo Javier. United States Environmental Protection Agency; Estados Unidos. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Ciudad Universitaria. Instituto de Química Biológica de la Facultad de Ciencias Exactas y Naturales. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales. Instituto de Química Biológica de la Facultad de Ciencias Exactas y Naturales; Argentina
Fil: DeVito, Michael J.. United States Environmental Protection Agency; Estados Unidos
Fil: Tornero-Velez, Rogelio. United States Environmental Protection Agency; Estados Unidos
Materia
Cumulative Risk
Motor Activity
Pyrethroids
Toxicokinetics
Nivel de accesibilidad
acceso abierto
Condiciones de uso
https://creativecommons.org/licenses/by-nc-sa/2.5/ar/
Repositorio
CONICET Digital (CONICET)
Institución
Consejo Nacional de Investigaciones Científicas y Técnicas
OAI Identificador
oai:ri.conicet.gov.ar:11336/66988
Acceder
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oai_identifier_str oai:ri.conicet.gov.ar:11336/66988
network_acronym_str CONICETDig
repository_id_str 3498
network_name_str CONICET Digital (CONICET)
spelling Environmentally relevant mixtures in cumulative assessments: An acute study of toxicokinetics and effects on motor activity in rats exposed to a mixture of pyrethroidsStarr, James M.Scollon, Edward J.Hughes, Michael F.Ross, David G.Graham, Stephen E.Crofton, Kevin M.Wolansky, Marcelo JavierDeVito, Michael J.Tornero-Velez, RogelioCumulative RiskMotor ActivityPyrethroidsToxicokineticshttps://purl.org/becyt/ford/1.4https://purl.org/becyt/ford/1https://purl.org/becyt/ford/3.3https://purl.org/becyt/ford/3Due to extensive use, human exposure to multiple pyrethroid insecticides occurs frequently. Studies of pyrethroid neurotoxicity suggest a common mode of toxicity and that pyrethroids should be considered cumulatively to model risk. The objective of this work was to use a pyrethroid mixture that reflects human exposure to common pyrethroids to develop comparative toxicokinetic profiles in rats, and then model the relationship between brain concentration and motor activity. Data from a national survey of child care centers were used to make a mixture reflecting proportions of the most prevalent pyrethroids: permethrin, cypermethrin, β-cyfluthrin, deltamethrin, and esfenvalerate. The mixture was administered orally at one of two concentrations (11.2 and 27.4 mg/kg) to adult male rats. At intervals from 1 to 24h, motor activity was assessed and the animals were sacrificed. Pyrethroid concentrations were measured in the blood, liver, fat, and brain. After controlling for dose, there were no differences in any tissue concentrations, except blood at the initial time point. Elimination half-lives for all pyrethroids in all tissues were < 7h. Brain concentrations of all pyrethroids (when cis- and trans-permethrin were pooled) at the initial time point were proportional to their relative doses. Decreases in motor activity indicated dose additivity, and the relationship between pyrethroid brain concentration and motor activity was described by a four-parameter sigmoidal Emax model. This study links environmental data with toxicokinetic and neurobehavioral assays to support cumulative risk assessments of pyrethroid pesticides. The results support the additive model of pyrethroid effect on motor activity and suggest that variation in the neurotoxicity of individual pyrethroids is related to toxicodynamic rather than toxicokinetic differences.Fil: Starr, James M.. United States Environmental Protection Agency; Estados UnidosFil: Scollon, Edward J.. United States Environmental Protection Agency; Estados UnidosFil: Hughes, Michael F.. United States Environmental Protection Agency; Estados UnidosFil: Ross, David G.. United States Environmental Protection Agency; Estados UnidosFil: Graham, Stephen E.. United States Environmental Protection Agency; Estados UnidosFil: Crofton, Kevin M.. United States Environmental Protection Agency; Estados UnidosFil: Wolansky, Marcelo Javier. United States Environmental Protection Agency; Estados Unidos. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Ciudad Universitaria. Instituto de Química Biológica de la Facultad de Ciencias Exactas y Naturales. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales. Instituto de Química Biológica de la Facultad de Ciencias Exactas y Naturales; ArgentinaFil: DeVito, Michael J.. United States Environmental Protection Agency; Estados UnidosFil: Tornero-Velez, Rogelio. United States Environmental Protection Agency; Estados UnidosOxford University Press2012-12info:eu-repo/semantics/articleinfo:eu-repo/semantics/publishedVersionhttp://purl.org/coar/resource_type/c_6501info:ar-repo/semantics/articuloapplication/pdfapplication/pdfhttp://hdl.handle.net/11336/66988Starr, James M.; Scollon, Edward J.; Hughes, Michael F.; Ross, David G.; Graham, Stephen E.; et al.; Environmentally relevant mixtures in cumulative assessments: An acute study of toxicokinetics and effects on motor activity in rats exposed to a mixture of pyrethroids; Oxford University Press; Toxicological Sciences; 130; 2; 12-2012; 309-3181096-6080CONICET DigitalCONICETenginfo:eu-repo/semantics/altIdentifier/doi/10.1093/toxsci/kfs245info:eu-repo/semantics/altIdentifier/url/https://academic.oup.com/toxsci/article/130/2/309/1724700info:eu-repo/semantics/openAccesshttps://creativecommons.org/licenses/by-nc-sa/2.5/ar/reponame:CONICET Digital (CONICET)instname:Consejo Nacional de Investigaciones Científicas y Técnicas2025-09-03T09:50:53Zoai:ri.conicet.gov.ar:11336/66988instacron:CONICETInstitucionalhttp://ri.conicet.gov.ar/Organismo científico-tecnológicoNo correspondehttp://ri.conicet.gov.ar/oai/requestdasensio@conicet.gov.ar; lcarlino@conicet.gov.arArgentinaNo correspondeNo correspondeNo correspondeopendoar:34982025-09-03 09:50:53.827CONICET Digital (CONICET) - Consejo Nacional de Investigaciones Científicas y Técnicasfalse
dc.title.none.fl_str_mv Environmentally relevant mixtures in cumulative assessments: An acute study of toxicokinetics and effects on motor activity in rats exposed to a mixture of pyrethroids
title Environmentally relevant mixtures in cumulative assessments: An acute study of toxicokinetics and effects on motor activity in rats exposed to a mixture of pyrethroids
spellingShingle Environmentally relevant mixtures in cumulative assessments: An acute study of toxicokinetics and effects on motor activity in rats exposed to a mixture of pyrethroids
Starr, James M.
Cumulative Risk
Motor Activity
Pyrethroids
Toxicokinetics
title_short Environmentally relevant mixtures in cumulative assessments: An acute study of toxicokinetics and effects on motor activity in rats exposed to a mixture of pyrethroids
title_full Environmentally relevant mixtures in cumulative assessments: An acute study of toxicokinetics and effects on motor activity in rats exposed to a mixture of pyrethroids
title_fullStr Environmentally relevant mixtures in cumulative assessments: An acute study of toxicokinetics and effects on motor activity in rats exposed to a mixture of pyrethroids
title_full_unstemmed Environmentally relevant mixtures in cumulative assessments: An acute study of toxicokinetics and effects on motor activity in rats exposed to a mixture of pyrethroids
title_sort Environmentally relevant mixtures in cumulative assessments: An acute study of toxicokinetics and effects on motor activity in rats exposed to a mixture of pyrethroids
dc.creator.none.fl_str_mv Starr, James M.
Scollon, Edward J.
Hughes, Michael F.
Ross, David G.
Graham, Stephen E.
Crofton, Kevin M.
Wolansky, Marcelo Javier
DeVito, Michael J.
Tornero-Velez, Rogelio
author Starr, James M.
author_facet Starr, James M.
Scollon, Edward J.
Hughes, Michael F.
Ross, David G.
Graham, Stephen E.
Crofton, Kevin M.
Wolansky, Marcelo Javier
DeVito, Michael J.
Tornero-Velez, Rogelio
author_role author
author2 Scollon, Edward J.
Hughes, Michael F.
Ross, David G.
Graham, Stephen E.
Crofton, Kevin M.
Wolansky, Marcelo Javier
DeVito, Michael J.
Tornero-Velez, Rogelio
author2_role author
author
author
author
author
author
author
author
dc.subject.none.fl_str_mv Cumulative Risk
Motor Activity
Pyrethroids
Toxicokinetics
topic Cumulative Risk
Motor Activity
Pyrethroids
Toxicokinetics
purl_subject.fl_str_mv https://purl.org/becyt/ford/1.4
https://purl.org/becyt/ford/1
https://purl.org/becyt/ford/3.3
https://purl.org/becyt/ford/3
dc.description.none.fl_txt_mv Due to extensive use, human exposure to multiple pyrethroid insecticides occurs frequently. Studies of pyrethroid neurotoxicity suggest a common mode of toxicity and that pyrethroids should be considered cumulatively to model risk. The objective of this work was to use a pyrethroid mixture that reflects human exposure to common pyrethroids to develop comparative toxicokinetic profiles in rats, and then model the relationship between brain concentration and motor activity. Data from a national survey of child care centers were used to make a mixture reflecting proportions of the most prevalent pyrethroids: permethrin, cypermethrin, β-cyfluthrin, deltamethrin, and esfenvalerate. The mixture was administered orally at one of two concentrations (11.2 and 27.4 mg/kg) to adult male rats. At intervals from 1 to 24h, motor activity was assessed and the animals were sacrificed. Pyrethroid concentrations were measured in the blood, liver, fat, and brain. After controlling for dose, there were no differences in any tissue concentrations, except blood at the initial time point. Elimination half-lives for all pyrethroids in all tissues were < 7h. Brain concentrations of all pyrethroids (when cis- and trans-permethrin were pooled) at the initial time point were proportional to their relative doses. Decreases in motor activity indicated dose additivity, and the relationship between pyrethroid brain concentration and motor activity was described by a four-parameter sigmoidal Emax model. This study links environmental data with toxicokinetic and neurobehavioral assays to support cumulative risk assessments of pyrethroid pesticides. The results support the additive model of pyrethroid effect on motor activity and suggest that variation in the neurotoxicity of individual pyrethroids is related to toxicodynamic rather than toxicokinetic differences.
Fil: Starr, James M.. United States Environmental Protection Agency; Estados Unidos
Fil: Scollon, Edward J.. United States Environmental Protection Agency; Estados Unidos
Fil: Hughes, Michael F.. United States Environmental Protection Agency; Estados Unidos
Fil: Ross, David G.. United States Environmental Protection Agency; Estados Unidos
Fil: Graham, Stephen E.. United States Environmental Protection Agency; Estados Unidos
Fil: Crofton, Kevin M.. United States Environmental Protection Agency; Estados Unidos
Fil: Wolansky, Marcelo Javier. United States Environmental Protection Agency; Estados Unidos. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Ciudad Universitaria. Instituto de Química Biológica de la Facultad de Ciencias Exactas y Naturales. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales. Instituto de Química Biológica de la Facultad de Ciencias Exactas y Naturales; Argentina
Fil: DeVito, Michael J.. United States Environmental Protection Agency; Estados Unidos
Fil: Tornero-Velez, Rogelio. United States Environmental Protection Agency; Estados Unidos
description Due to extensive use, human exposure to multiple pyrethroid insecticides occurs frequently. Studies of pyrethroid neurotoxicity suggest a common mode of toxicity and that pyrethroids should be considered cumulatively to model risk. The objective of this work was to use a pyrethroid mixture that reflects human exposure to common pyrethroids to develop comparative toxicokinetic profiles in rats, and then model the relationship between brain concentration and motor activity. Data from a national survey of child care centers were used to make a mixture reflecting proportions of the most prevalent pyrethroids: permethrin, cypermethrin, β-cyfluthrin, deltamethrin, and esfenvalerate. The mixture was administered orally at one of two concentrations (11.2 and 27.4 mg/kg) to adult male rats. At intervals from 1 to 24h, motor activity was assessed and the animals were sacrificed. Pyrethroid concentrations were measured in the blood, liver, fat, and brain. After controlling for dose, there were no differences in any tissue concentrations, except blood at the initial time point. Elimination half-lives for all pyrethroids in all tissues were < 7h. Brain concentrations of all pyrethroids (when cis- and trans-permethrin were pooled) at the initial time point were proportional to their relative doses. Decreases in motor activity indicated dose additivity, and the relationship between pyrethroid brain concentration and motor activity was described by a four-parameter sigmoidal Emax model. This study links environmental data with toxicokinetic and neurobehavioral assays to support cumulative risk assessments of pyrethroid pesticides. The results support the additive model of pyrethroid effect on motor activity and suggest that variation in the neurotoxicity of individual pyrethroids is related to toxicodynamic rather than toxicokinetic differences.
publishDate 2012
dc.date.none.fl_str_mv 2012-12
dc.type.none.fl_str_mv info:eu-repo/semantics/article
info:eu-repo/semantics/publishedVersion
http://purl.org/coar/resource_type/c_6501
info:ar-repo/semantics/articulo
format article
status_str publishedVersion
dc.identifier.none.fl_str_mv http://hdl.handle.net/11336/66988
Starr, James M.; Scollon, Edward J.; Hughes, Michael F.; Ross, David G.; Graham, Stephen E.; et al.; Environmentally relevant mixtures in cumulative assessments: An acute study of toxicokinetics and effects on motor activity in rats exposed to a mixture of pyrethroids; Oxford University Press; Toxicological Sciences; 130; 2; 12-2012; 309-318
1096-6080
CONICET Digital
CONICET
url http://hdl.handle.net/11336/66988
identifier_str_mv Starr, James M.; Scollon, Edward J.; Hughes, Michael F.; Ross, David G.; Graham, Stephen E.; et al.; Environmentally relevant mixtures in cumulative assessments: An acute study of toxicokinetics and effects on motor activity in rats exposed to a mixture of pyrethroids; Oxford University Press; Toxicological Sciences; 130; 2; 12-2012; 309-318
1096-6080
CONICET Digital
CONICET
dc.language.none.fl_str_mv eng
language eng
dc.relation.none.fl_str_mv info:eu-repo/semantics/altIdentifier/doi/10.1093/toxsci/kfs245
info:eu-repo/semantics/altIdentifier/url/https://academic.oup.com/toxsci/article/130/2/309/1724700
dc.rights.none.fl_str_mv info:eu-repo/semantics/openAccess
https://creativecommons.org/licenses/by-nc-sa/2.5/ar/
eu_rights_str_mv openAccess
rights_invalid_str_mv https://creativecommons.org/licenses/by-nc-sa/2.5/ar/
dc.format.none.fl_str_mv application/pdf
application/pdf
dc.publisher.none.fl_str_mv Oxford University Press
publisher.none.fl_str_mv Oxford University Press
dc.source.none.fl_str_mv reponame:CONICET Digital (CONICET)
instname:Consejo Nacional de Investigaciones Científicas y Técnicas
reponame_str CONICET Digital (CONICET)
collection CONICET Digital (CONICET)
instname_str Consejo Nacional de Investigaciones Científicas y Técnicas
repository.name.fl_str_mv CONICET Digital (CONICET) - Consejo Nacional de Investigaciones Científicas y Técnicas
repository.mail.fl_str_mv dasensio@conicet.gov.ar; lcarlino@conicet.gov.ar
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score 13.13397

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