Marcelo J. Wolansky, Chris Gennings,
Michael J. DeVito, and Kevin M. Crofton
doi: 10.1289/ehp.0900667 (available at http://dx.doi.org/)
Online 8 June 2009
Background: Pyrethroids are neurotoxic insecticides used in a variety of
indoor and outdoor
applications. The current work tested the hypothesis that cumulative
neurotoxic effects of
pyrethroid mixtures are predicted using the default dose-addition theory.
characterized the acute dose-effect functions for eleven pyrethroids
administered orally in corn
oil (1 ml/kg) based on assessment of motor activity.
Objectives: The hypothesis was tested using a mixture of the eleven
pyrethroids and the same
testing paradigm used in single compound assays.
Methods: Mixing ratios in the tested mixture were based on the individual
chemical ED30s (i.e.,
the mixture comprised equipotent amounts of each pyrethroid). The highest
each individual chemical in the mixture was below the threshold for inducing
Adult male rats received acute oral exposure to corn oil (control) or
dilutions of the stock
mixture solution. The mixture of eleven pyrethroids was administered either
simultaneously (2 hr
before testing) or following a sequence based on times of peak effect for
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 sub-threshold doses of individual chemicals were combined in
significant dose-related decreases in motor activity were found. Further, no
departure from the
predicted dose-additive curve was found regardless of the mixture dosing
Conclusion: This study shows the first in vivo evidence on pyrethroid
supporting the default assumption of dose-addition.