Behavioral Alterations Induced in Rats by a Pre- and Postnatal Exposure to 2,4-Dichlorophenoxyacetic Acid

doi:10.1016/S0892-0362(98)00059-2

Neurotoxicology and Teratology

Volume 21, Issue 4, July–August 1999, Pages 451-465

https://doi.org/10.1016/S0892-0362(98)00059-2 Get rights and content

Abstract

The purpose of this study was to determine whether the behavioral development pattern was altered by a pre- and postnatal exposure to 2,4-Dichlorophenoxyacetic acid (2,4-D). Pregnant rats were daily orally exposed to 70 mg/kg/day of 2,4-D from gestation day (GD) 16 to postnatal day (PND) 23. After weaning, the pups were assigned to one of the two subgroups: T1 (fed with untreated diet until PND 90) and T2 (maintained with 2,4-D diet until PND 90). Effects on offsprings were evaluated with a neurotoxicological test battery. Neuromotor reflexes, spontaneous motor activity, serotonin syndrome, circling, and catalepsy were analyzed during various postnatal ages. 2,4-D neonatal exposure induced delay of the ontogeny of righting reflex and negative geotaxis accompanied by motor abnormalities, stereotypic behaviors (excessive grooming and vertical head movements), and hyperactivity in the open field. Adult rats of both sexes (T2 group) showed a diminution of ambulation and rearing, while excessive grooming responses were only observed in T2 males. Besides, these animals manifested serotonin syndrome behaviors, catalepsy, and right-turning preference. Some behaviors were reversible, but others were permanent, and some were only expressed after pharmacological challenges.

Section snippets

Animals and Exposure to 2,4-D

Nulliparous female Wistar rats, approximately 3 months of age, were separately placed with fertile males on the proestrus night, and the presence of spermatozoa was checked in the vaginal smear the following morning. This day was denoted as gestation day 0 (GD 0). At this time, pregnant females were individually housed in plastic breeding cages in a temperature-controlled nursery (22–24°C) and maintained on a 12-h light/dark cycle. Food and water were available ad lib. In GD 16, the pregnant

Animal Weights and Physical Landmarks

Maternal exposure to 70 mg/kg/day 2,4-D had no effect on maternal body weight gain during gestation or lactation, on the number of pups born or on postnatal mortality. Further, no measurable effects of 2,4-D exposure during pregnancy and lactation on maternal nesting behavior were detected (data not shown). However, there was a significant main effect for exposure on pup weight (Fig. 1). Significant reductions in weight gain were observed from PND 7 to PND 23 in 2,4-D–exposed pups of both sexes

Discussion

Although the nonobserved adverse-effect level (NOAEL) for chronic dietary neurotoxicity was considered to be only the retinal degeneration and increased relative forelimb grip strength in rats for 75 mg/kg/day for 2,4-D (32), our present results indicate that pre- and postnatal exposure to about 70 mg/kg/day 2,4-D modifies the behavioral pattern in developing, young, and adult rats. The observed behavioral alterations were not accompanied by external signs of overt toxicity such as changes on

Acknowledgements

This research was supported by a grant from the Consejo Nacional de Investigaciones Cientı́fı́cas y Técnicas (CONICET), Argentina to Ana Marı́a Evangelista de Duffard. The authors thank Aurelia Vicens de Robson for linguistic assistance.

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ArticlesBehavioral Alterations Induced in Rats by a Pre- and Postnatal Exposure to 2,4-Dichlorophenoxyacetic Acid

Abstract

Section snippets

Animals and Exposure to 2,4-D

Animal Weights and Physical Landmarks

Discussion

Acknowledgements

Anim. Behav.

Anim. Behav.

Behav. Brain Res.

Neuropharmacology

Neurotoxicol. Teratol.

Brain Res.

Pharmacol. Ther.

Biochem. Pharmacol.

Neurotoxicol. Teratol.

Neurotoxicol. Teratol.

Eur. J. Pharmacol.

Brain Res.

Brain Res.

Fundam. Appl. Toxicol.

Eur. J. Pharmacol.

Toxicol. Lett.

Pharmacol. Biochem. Behav.

Pharmacol. Biochem. Behav.

Pharmacol. Biochem. Behav.

Neurotoxicol. Teratol.

Brain Res.

Pharmacol. Biochem. Behav.

Behav. Brain Res.

Food Cosmet. Toxicol.

Brain Res.

Enzime Microbiol. Technol.

Neurosci. Lett.

Eur. J. Pharmacol.

Teratongenic and enbryotoxic effects of the herbicide di and trichlorophenoxyacetic acids (2,4-D and 2,4,5-T)

Acta Pharmacol. Toxicol.

Articles
Behavioral Alterations Induced in Rats by a Pre- and Postnatal Exposure to 2,4-Dichlorophenoxyacetic Acid