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Evidence for Dose-Additive Effects of Pyrethroids on Motor Activity in Rats.

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Title: Evidence for Dose-Additive Effects of Pyrethroids on Motor Activity in Rats.
Authors: Wolansky, Marcelo J.1, Gennings, Chris2, DeVito, Michael J.3, Crofton, Kevin M.4 crofton.kevin@epa.gov
Source: Environmental Health Perspectives. Oct2009, Vol. 117 Issue 10, p1563-1570. 8p. 5 Charts, 2 Graphs.
Subject Terms: *Pyrethroids, *Physiological effects of insecticides, *Dose-response relationship in biochemistry, *Solution (Chemistry), Motor ability, Neurotoxicology, Corn oil, Numerical analysis, Laboratory rats
Abstract: 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. [ABSTRACT FROM AUTHOR]
Copyright of Environmental Health Perspectives is the property of National Institute of Environmental Health Sciences and its content may not be copied or emailed to multiple sites without the copyright holder's express written permission. Additionally, content may not be used with any artificial intelligence tools or machine learning technologies. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)
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  Data: Evidence for Dose-Additive Effects of Pyrethroids on Motor Activity in Rats.
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  Data: <searchLink fieldCode="AR" term="%22Wolansky%2C+Marcelo+J%2E%22">Wolansky, Marcelo J.</searchLink><relatesTo>1</relatesTo><br /><searchLink fieldCode="AR" term="%22Gennings%2C+Chris%22">Gennings, Chris</searchLink><relatesTo>2</relatesTo><br /><searchLink fieldCode="AR" term="%22DeVito%2C+Michael+J%2E%22">DeVito, Michael J.</searchLink><relatesTo>3</relatesTo><br /><searchLink fieldCode="AR" term="%22Crofton%2C+Kevin+M%2E%22">Crofton, Kevin M.</searchLink><relatesTo>4</relatesTo><i> crofton.kevin@epa.gov</i>
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  Data: <searchLink fieldCode="JN" term="%22Environmental+Health+Perspectives%22">Environmental Health Perspectives</searchLink>. Oct2009, Vol. 117 Issue 10, p1563-1570. 8p. 5 Charts, 2 Graphs.
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  Data: *<searchLink fieldCode="DE" term="%22Pyrethroids%22">Pyrethroids</searchLink><br />*<searchLink fieldCode="DE" term="%22Physiological+effects+of+insecticides%22">Physiological effects of insecticides</searchLink><br />*<searchLink fieldCode="DE" term="%22Dose-response+relationship+in+biochemistry%22">Dose-response relationship in biochemistry</searchLink><br />*<searchLink fieldCode="DE" term="%22Solution+%28Chemistry%29%22">Solution (Chemistry)</searchLink><br /><searchLink fieldCode="DE" term="%22Motor+ability%22">Motor ability</searchLink><br /><searchLink fieldCode="DE" term="%22Neurotoxicology%22">Neurotoxicology</searchLink><br /><searchLink fieldCode="DE" term="%22Corn+oil%22">Corn oil</searchLink><br /><searchLink fieldCode="DE" term="%22Numerical+analysis%22">Numerical analysis</searchLink><br /><searchLink fieldCode="DE" term="%22Laboratory+rats%22">Laboratory rats</searchLink>
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  Data: 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. [ABSTRACT FROM AUTHOR]
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  Data: <i>Copyright of Environmental Health Perspectives is the property of National Institute of Environmental Health Sciences and its content may not be copied or emailed to multiple sites without the copyright holder's express written permission. Additionally, content may not be used with any artificial intelligence tools or machine learning technologies. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract.</i> (Copyright applies to all Abstracts.)
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      – SubjectFull: Pyrethroids
        Type: general
      – SubjectFull: Physiological effects of insecticides
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      – SubjectFull: Dose-response relationship in biochemistry
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      – SubjectFull: Solution (Chemistry)
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      – SubjectFull: Motor ability
        Type: general
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      – SubjectFull: Corn oil
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      – SubjectFull: Numerical analysis
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      – SubjectFull: Laboratory rats
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      – TitleFull: Evidence for Dose-Additive Effects of Pyrethroids on Motor Activity in Rats.
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              Text: Oct2009
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