Elsevier

NeuroToxicology

Volume 27, Issue 3, May 2006, Pages 421-428
NeuroToxicology

Effects of permethrin given before mating on the behavior of F1-generation in mice

https://doi.org/10.1016/j.neuro.2005.12.001Get rights and content

Abstract

Permethrin, a type I synthetic pyrethroid insecticide, was evaluated through assessment of the behavioral development of F1 progeny of mice. Groups each of 30 male and 30 female ICR (CD-1) mice, as F0-generation, were given 0, 4.9, 9.8, and 19.6 mg/kg/d permethrin by gavage for 4 weeks before mating. Behavioral endpoints of motor reflexes, motor coordination, and activity were evaluated in F1 progeny. Clinical signs of toxicity including salivation, hyperactivity, and liquid feces which attributed to permethrin were observed in the F0-mice treated with 9.8 and 19.6 mg/kg/d. Reduction of body weight became evident only during gestation and lactation periods for the middle and high dose groups. Significant differences in the development of reflexes, swimming ability, and open field activity were evident in the offspring for the 9.8 and 19.6 mg/kg/d dose groups compared to the control group. These results show that permethrin at dose levels of 9.8 and 19.6 mg/kg/d can induce a significant risk to the offspring following treatment of F0-mice before mating. The NOEL obtained in this study for the effects of permethrin on the development of the F1-progeny is 4.9 mg/kg/d.

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.

References (42)

  • D.B. Peele et al.

    Pyrethroid effects on schedule controlled behavior: time and dosage relationship

    Neurotoxicol Teratol

    (1987)
  • R.D. Porsolt et al.

    Behavioral despair in rats: a new model sensitive to antidepressant treatments

    Eur J Pharmacol

    (1978)
  • R.D. Porsolt et al.

    Immobility induced by forced swimming in rats: effects of agents which modify central catecholamines and serotonin activity

    Eur J Pharmacol

    (1979)
  • D.M. Soderlund et al.

    Mechanisms of pyrethroid neurotoxicity: implications for cumulative risk assessment

    Toxicology

    (2002)
  • E.A. Stein et al.

    Effects of pyrethroid insecticides on operant responding maintained by food

    Neurotoxicol Teratol

    (1987)
  • P.M. Adams

    Effects of perinatal chlordiazepoxide exposure on rat preweaning and post weaning behavior

    Neurobehav Toxicol Teratol

    (1982)
  • S. Alder et al.

    Methods for the evaluation of physical, neuromuscular, and behavioral development of rats in early postnatal life

  • A.S. Bloom et al.

    Pyrethroid effects on operant responding and feeding

    Neurobehav Toxicol Teratol

    (1983)
  • J.R. Bloomquist

    Ion channels as targets for insecticides

    Ann Rev Entomol

    (1996)
  • S.P. Bradbury et al.

    Comparative toxicology of the pyrethroid insecticides

    Rev Environ Contam Toxicol

    (1989)
  • R.E. Butcher et al.

    A preliminary test battery for the investigation of the behavioral teratology of selected psychotropic drugs

    Neurobehav Toxicol

    (1979)
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