Evidence for dose-additive effects of pyrethroids on motor activity in rats

BACKGROUND: Pyrethroids are neurotoxic insecticides used in a variety of indoor and outdoor applications. Previous research characterized the acute dose-effect functions for 11 pyrethroids administered orally in corn oil (1 mL/kg) based on assessment of motor activity. OBJECTIVES: We used a mixture...

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Autor principal:	Wolansky, Marcelo Javier
Publicado:	2009
Materias:	Additivity Cumulative Mixtures Neurotoxicity Pyrethroids bifenthrin bioallethrin cipermethrin cyfluthrin cyhalothrin deltamethrin fenpropathrin fenvalerate permethrin pyrethroid resmethrin animal experiment animal model article controlled study in vivo study male maximum allowable concentration motor activity motor dysfunction neurotoxicity nonhuman prediction priority journal rat Animals Dose-Response Relationship, Drug Insecticides Male Motor Activity Pyrethrins Rats Rats, Long-Evans Rattus Zea mays
Acceso en línea:	https://bibliotecadigital.exactas.uba.ar/collection/paper/document/paper_00916765_v117_n10_p1563_Wolansky http://hdl.handle.net/20.500.12110/paper_00916765_v117_n10_p1563_Wolansky
Aporte de:	Biblioteca Digital - Facultad de Ciencias Exactas y Naturales (UBA) de Universidad de Buenos Aires

id	paper:paper_00916765_v117_n10_p1563_Wolansky
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spelling	paper:paper_00916765_v117_n10_p1563_Wolansky2023-06-08T15:08:09Z Evidence for dose-additive effects of pyrethroids on motor activity in rats Wolansky, Marcelo Javier Additivity Cumulative Mixtures Neurotoxicity Pyrethroids bifenthrin bioallethrin cipermethrin cyfluthrin cyhalothrin deltamethrin fenpropathrin fenvalerate permethrin pyrethroid resmethrin animal experiment animal model article controlled study in vivo study male maximum allowable concentration motor activity motor dysfunction neurotoxicity nonhuman prediction priority journal rat Animals Dose-Response Relationship, Drug Insecticides Male Motor Activity Pyrethrins Rats Rats, Long-Evans Rattus Zea mays BACKGROUND: Pyrethroids are neurotoxic insecticides used in a variety of indoor and outdoor applications. Previous research characterized the acute dose-effect functions for 11 pyrethroids administered orally in corn oil (1 mL/kg) based on assessment of motor activity. OBJECTIVES: We used a mixture of these 11 pyrethroids and the same testing paradigm used in single-compound assays to test the hypothesis that cumulative neurotoxic effects of pyrethroid mixtures can be predicted using the default dose-addition theory. METHODS: Mixing ratios of the 11 pyrethroids in the tested mixture were based on the ED30 (effective dose that produces a 30% decrease in response) of the individual chemical (i.e., the mixture comprised equipotent amounts of each pyrethroid). The highest concentration of each individual chemical in the mixture was less than the threshold for inducing behavioral effects. Adult male rats received acute oral exposure to corn oil (control) or dilutions of the stock mixture solution. The mixture of 11 pyrethroids was administered either simultaneously (2 hr before testing) or after a sequence based on times of peak effect for the individual chemicals (4, 2, and 1 hr before testing). A threshold additivity model was fit to the single-chemical data to predict the theoretical dose-effect relationship for the mixture under the assumption of dose additivity. RESULTS: When subthreshold doses of individual chemicals were combined in the mixtures, we found significant dose-related decreases in motor activity. Further, we found no departure from the predicted dose-additive curve regardless of the mixture dosing protocol used. CONCLUSION: In this article we present the first in vivo evidence on pyrethroid cumulative effects supporting the default assumption of dose addition. Fil:Wolansky, M.J. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales; Argentina. 2009 https://bibliotecadigital.exactas.uba.ar/collection/paper/document/paper_00916765_v117_n10_p1563_Wolansky http://hdl.handle.net/20.500.12110/paper_00916765_v117_n10_p1563_Wolansky
institution	Universidad de Buenos Aires
institution_str	I-28
repository_str	R-134
collection	Biblioteca Digital - Facultad de Ciencias Exactas y Naturales (UBA)
topic	Additivity Cumulative Mixtures Neurotoxicity Pyrethroids bifenthrin bioallethrin cipermethrin cyfluthrin cyhalothrin deltamethrin fenpropathrin fenvalerate permethrin pyrethroid resmethrin animal experiment animal model article controlled study in vivo study male maximum allowable concentration motor activity motor dysfunction neurotoxicity nonhuman prediction priority journal rat Animals Dose-Response Relationship, Drug Insecticides Male Motor Activity Pyrethrins Rats Rats, Long-Evans Rattus Zea mays
spellingShingle	Additivity Cumulative Mixtures Neurotoxicity Pyrethroids bifenthrin bioallethrin cipermethrin cyfluthrin cyhalothrin deltamethrin fenpropathrin fenvalerate permethrin pyrethroid resmethrin animal experiment animal model article controlled study in vivo study male maximum allowable concentration motor activity motor dysfunction neurotoxicity nonhuman prediction priority journal rat Animals Dose-Response Relationship, Drug Insecticides Male Motor Activity Pyrethrins Rats Rats, Long-Evans Rattus Zea mays Wolansky, Marcelo Javier Evidence for dose-additive effects of pyrethroids on motor activity in rats
topic_facet	Additivity Cumulative Mixtures Neurotoxicity Pyrethroids bifenthrin bioallethrin cipermethrin cyfluthrin cyhalothrin deltamethrin fenpropathrin fenvalerate permethrin pyrethroid resmethrin animal experiment animal model article controlled study in vivo study male maximum allowable concentration motor activity motor dysfunction neurotoxicity nonhuman prediction priority journal rat Animals Dose-Response Relationship, Drug Insecticides Male Motor Activity Pyrethrins Rats Rats, Long-Evans Rattus Zea mays
description	BACKGROUND: Pyrethroids are neurotoxic insecticides used in a variety of indoor and outdoor applications. Previous research characterized the acute dose-effect functions for 11 pyrethroids administered orally in corn oil (1 mL/kg) based on assessment of motor activity. OBJECTIVES: We used a mixture of these 11 pyrethroids and the same testing paradigm used in single-compound assays to test the hypothesis that cumulative neurotoxic effects of pyrethroid mixtures can be predicted using the default dose-addition theory. METHODS: Mixing ratios of the 11 pyrethroids in the tested mixture were based on the ED30 (effective dose that produces a 30% decrease in response) of the individual chemical (i.e., the mixture comprised equipotent amounts of each pyrethroid). The highest concentration of each individual chemical in the mixture was less than the threshold for inducing behavioral effects. Adult male rats received acute oral exposure to corn oil (control) or dilutions of the stock mixture solution. The mixture of 11 pyrethroids was administered either simultaneously (2 hr before testing) or after a sequence based on times of peak effect for the individual chemicals (4, 2, and 1 hr before testing). A threshold additivity model was fit to the single-chemical data to predict the theoretical dose-effect relationship for the mixture under the assumption of dose additivity. RESULTS: When subthreshold doses of individual chemicals were combined in the mixtures, we found significant dose-related decreases in motor activity. Further, we found no departure from the predicted dose-additive curve regardless of the mixture dosing protocol used. CONCLUSION: In this article we present the first in vivo evidence on pyrethroid cumulative effects supporting the default assumption of dose addition.
author	Wolansky, Marcelo Javier
author_facet	Wolansky, Marcelo Javier
author_sort	Wolansky, Marcelo Javier
title	Evidence for dose-additive effects of pyrethroids on motor activity in rats
title_short	Evidence for dose-additive effects of pyrethroids on motor activity in rats
title_full	Evidence for dose-additive effects of pyrethroids on motor activity in rats
title_fullStr	Evidence for dose-additive effects of pyrethroids on motor activity in rats
title_full_unstemmed	Evidence for dose-additive effects of pyrethroids on motor activity in rats
title_sort	evidence for dose-additive effects of pyrethroids on motor activity in rats
publishDate	2009
url	https://bibliotecadigital.exactas.uba.ar/collection/paper/document/paper_00916765_v117_n10_p1563_Wolansky http://hdl.handle.net/20.500.12110/paper_00916765_v117_n10_p1563_Wolansky
work_keys_str_mv	AT wolanskymarcelojavier evidencefordoseadditiveeffectsofpyrethroidsonmotoractivityinrats
_version_	1768543412215087104

Evidence for dose-additive effects of pyrethroids on motor activity in rats

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