Effects of permethrin given before mating on the behavior of F1-generation in mice
Introduction
Synthetic pyrethroid insecticides have been used in agriculture and home formulations for more than 30 years and account for approximately one-fourth of the worldwide insecticide market (Casida and Quistad, 1998). The action of pyrethroid insecticides has been divided into two types (I and II) based on signs and neurophysiologic effects (Laurence and Casida, 1983, Verschoyle and Aldridge, 1980). Generally, the two types can be distinguished structurally by the presence (type II) or absence (type I) of an alpha-cyano substituent. The acute mammalian neurotoxicity of pyrethroids has been well characterized, and several comprehensive reviews of pyrethroid toxicity and actions are available (De Ray, 2001, Kaneko and Miyamoto, 2001, Narahashi, 2001, Shafer et al., 2005, Soderlund et al., 2002). Aspects of open-field behavior and catalepsy (Mandhane and Chopde, 1997), conditioned behavior (Moniz et al., 1994); operant behavior (Stein et al., 1987), schedule-controlled behavior (Peele and Crofton, 1987), motor activity (McDaniel and Moser, 1993), and others can be altered by pyrethroid exposure in adult animals. Neonatal exposure of mice to deltamethrin and bioallethrin increased motor activity in adult age and decreased the density of cortical cholinergic muscarinic receptor (Eriksson and Fredriksson, 1991). Maternal exposure to cyhalothrin during lactation disrupted passive avoidance learning during adulthood (Gomes et al., 1991a), and delayed the descent of the tests in male offspring (Gomes et al., 1991b). Fenvalerate, a type II pyrethroid, was capable of interfering with reproductive parameters of male and female rats (Moniz et al., 1999), and affected the developmental of physical and behavior in infant and adult rats (Moniz et al., 1990).
Permethrin [3-(2,2-dichloroethenyl)-2,2-dimethylcylo-propane carboxylic acid (3-phenoxyphenyl) methyl ester], a type I synthetic pyrethroid insecticide, is a mixture of four (1R, S-cis and 1R, S-trans) isomers, only one of which (1R, -cis) has lethal effects in mammals (Casida et al., 1983). It provides insecticidal activity for several weeks following a single application and is used to control fleas, flies, mites, and cockroaches (Abou-Donia et al., 2004). Permethrin causes modification of sodium channels leading to prolonged depolarization and repetitive discharges in presynaptic nerve fibers after a single stimulus (Bloomquist, 1996, Narahashi, 1985). This repetitive nerve action is associated with tremor, hyperactivity, ataxia, convulsions, and in some cases paralysis. At low dosage-dependent decrease in locomotor activity and an increase in the amplitude of the startle response to an acoustic stimulus following exposure of rats to repeated doses of permethrin for 30 days (Crofen and Reiter, 1988). Exposure of male mice to Ambush (25.6% permethrin) for 30 min increased activities like chewing (Mitchell et al., 1988). In addition rats exposure to permethrin at two time points on the day of dosing increased aggressive behavior, agitation, resistance to being captured, reactivity to a click stimulus, and induced head and forelimb shaking (McDaniel and Moser, 1993), and disrupted a learning feeding behavior in rats at doses about 20% of LD50 after repeated doses for 30 days (Peele and Crofton, 1987). Furthermore, permethrin can have significant effects on learned behavior, food intake, and decrease in operant response rate in rats after exposure for 20 min (Bloom et al., 1983). Exposure of rats to permethrin for 60 days led to sensorimotor deficits and differential aberrations of the cholinergic system in the CNS (Abou-Donia et al., 2004). There is no information regarding the potential effects of permethrin on the behavior and physical development endpoints on the progeny. The aim of the present study was to evaluate the effects of F0-male and female mice exposure to permethrin before mating for 20 days on the development of physical and behavioral aspects in the offsprings at dose levels: one that induces some toxicity on F0-mice, one unable to induce toxicity and an intermediate one. These doses were approximately equal to 1/100, 1/50, and 1/25 of acute oral LD50 for permethrin (40:60 cis/trans) in mice (FAO/WHO, 1999).
Section snippets
Test material
Technical grade permethrin (60:40, trans:cis; 94% purity) was kindly donated by El-Watania, Inc., Alexandria, Egypt.
Test species and husbandry
One hundred and twenty Male and 120 female ICR (CD-1) mice, approximately 10 weeks old, were obtained from the High Institute of Public Health, Alexandria University, Alexandria, Egypt. Mice were examined for health status and acclimated to the laboratory environment for 2 weeks prior to use. The animal room was designed to maintain temperature 23 ± 2 °C, relative humidity at
Clinical observations
There were two, three, two, and one of F0-males died in the groups of control, 4.9, 9.8, and 19.6 mg/kg/d, respectively, during the course of the treatment. Two of F0-females of the treated group 4.9 mg/kg/d died during the course of the treatment. Although there was no death in the pregnant females, two, one, four, and four females died in the control, 4.9, 9.8, and 19.6 mg/kg/d, respectively, during the lactation period. Administration of 4.9 mg/kg/d of permethrin dose did not produce any
Discussion
To our knowledge some studies have been reported about the effects of permethrin on the behavior of adult mammals (Abou-Donia et al., 2004, Bloom et al., 1983, Crofen and Reiter, 1988, McDaniel and Moser, 1993, Mitchell et al., 1988, Peele and Crofton, 1987) and this is the first study to evaluate the effects on the behavior of F1-progeny following exposure of parents before mating. In the present study, the NOEL obtained developmental effects of permethrin was 4.9 mg/kg/d. This dose was unable
Conclusion
The present data demonstrate that permethrin can produce behavioral alterations in F1-mice offspring for F0-mice toxic doses 9.8 and 19.6 mg/kg/d. These behavioral effects are most likely due to maternal toxicity and stunt of growth of the pups rather than the neurotoxicity of permethrin. No evidence of F0-mice toxicity and F1-offspring's development was observed at 4.9 mg/kg/d.
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