You are here:
Comments on: "Perinatal toxicity of cyfluthrin in Mice: developmental and behavioral effects" by Soni et al, which is accepted in Human & Experimental Toxicology (DOl: 10.1177/0960327110391386)
Citation:
SHAFER, TIM AND K. M. CROFTON. Comments on: "Perinatal toxicity of cyfluthrin in Mice: developmental and behavioral effects" by Soni et al, which is accepted in Human & Experimental Toxicology (DOl: 10.1177/0960327110391386). HUMAN AND EXPERIMENTAL TOXICOLOGY. MacMillan Magazines LIMITED, London, Uk, 30(8):1112-3, (2011).
Impact/Purpose:
While the premise of the manuscript by Soni and colleagues is laudable, we are compelled to write this letter because the study design used by Soni and colleagues has serious flaws that prevent any conclusions about the possible developmental neurotoxicity of cyfluthrin.
Description:
Soni and colleagues recently reported that perinatal maternal exposure to cyfluthrin, a pyrethroid insecticide, caused fetal malformations and behavioral changes in offspring, including skeletal malformations and alterations in righting reflexes and locomotion (Soni et al., 2011). In this study, the authors exposed dams to 0,16 or 32 mg/kg SOLFAC 050 EW®, (an emulsion concentrate containing 5% cyfluthrin) from gestation day 14 through weaning on postnatal day 21. One half of the dams were sacrificed on GD18 and litters examined for fetal anomalies, and the other half of the dams were allowed to deliver and offspring evaluated for behavioral changes through postnatal day 60. While the premise of the manuscript by Soni and colleagues is laudable, we are compelled to write this letter because the study design used by Soni and colleagues has serious flaws that prevent any conclusions about the possible developmental neurotoxicity of cyfluthrin. The major problem with this paper is the inability to determine the chemical agent, or agents, responsible for the teratological and/or behavioral effects in the offspring. In this study, the pregnant and lactating rats were exposed to a commercial formulation of cyfluthrin that contains 95% unknown "inerts". According to a manufacturer's label for this product, it may contain as much as 9% (%W/W) aromatic hydrocarbons and 9% "stabilizers". Aromatic hydrocarbons such as toluene and xylene are well known neurotoxicants, and there is evidence for developmental neurotoxicity associated with exposure to these solvents (Donald et al., 1991; Hass et al., 1999; Till et al., 2005; Bowen and Hannigan, 2006).The authors conclude in the paper that: " ... the tested doses of cyfluthrin are not embryotoxic but elicit significant toxicity on the behavior of neonates". The problem with this conclusion is that the exposure was not solely to cyfluthrin, and the vehicle control (tap water only) was insufficient because it did not contain the inerts. Therefore, it is impossible to determine whether any effects are due to the cyfluthrin, the other inerts or their combination. Because of this serious confound the authors' conclusions that the effects can be attributed solely to cyfluthrin exposure cannot be supported. An additional issue with this study also limits interpretation of the data; Soni and colleagues do not clearly report the numbers of pups utilized in the behavioral studies and do not describe in sufficient detail the statistical design of the behavioral studies. Of particular importance here is whether or not a "litter-based" design was used for the behavioral studies. Without adequately describing the number of animals utilized in each behavioral test, as well as describing fully the origin of the animals (with respect to litter) and statistical analysis ofthe data, it is impossible for the reader tolrnow whether or not the issue of litter was properly controlled for as a variable. The sampling ofmultiple pups from the same litter inflates the sample size and increases the probability of a type I statistical error (Abbey and Howard 1973; Holson and Pearce 1992; Muller et aI. 1985; Reily and Meyer 1984; Holson et aI., 2008). The issues associated with the shortcomings of the paper by Soni and colleagues have been raised previously concerning developmental exposures to pyrethroids (Shafer et aI., 2005; Crofton et al 2007), but apply to toxicity studies with any chemical. We beseech both authors and editorial boards to be cognizant of these issues in the future. Concluding that the effects reported in this paper are due solely, or even partially, to cyfluthrin exposure is not possible due to the confounding issues raised above. We applaud the intentions of Soni and colleagues to address an important concern regarding the safety of this class of compounds to developing individuals. By pointing out the limitations of this study, we hope that future studies by these and other groups will be able to address the question of pyrethroid developmental neurotoxicity more definitively. *This document has been reviewed in accordance with the U.S. Environmental Protection Agency policy and approved for publication. Approval does not signify that the comments reflect the views of the Agency, nor does mention of trade names or commercial products does not constitute endorsement or recommendation for use.
