Long-lasting neurotoxicity of prenatal benzene acute exposure in rats

Benzene is a common element of environmental pollution. Although this substance is not recognized as a teratogenic agent, it is not known whether prenatal exposure to benzene may induce neurobehavioral changes in the progeny. Benzene 0.1 mg/kg was injected subcutaneously (s.c.) acutely at day 15 of gestation into pregnant female rats of the Sprague-Dawley strain and neurotoxicity of the substance was studied in pups and male adult animals of the same progeny. No change was found in total number of neonates, body weight and eye opening time between benzene-exposed animals and controls. No malformations were observed. At birth, neonatal reflexes (cliff aversion, forelimb placing, bar holding, forelimb grasping, startle) were scored in benzene-exposed pups and their percent appearance was found to be anticipated (more benzene-exposed pups exhibited reflexes each day) in comparison to that of control animals. Also, the completion (maximum appearance, i.e. 100% of the brood was found to exhibit each reflex) of neonatal reflexes in benzene-exposed animals preceded that of controls. Starting 2 months after birth, cognitive and motor performance was assessed only in male animals of the prenatally benzene-exposed progeny. The overall evaluation of motor activity in benzene-exposed animals in the open-field test revealed reduced ambulation in these rats as compared to control animals. Acquisition of active avoidance responses in the shuttle-box test, as assessed by the number of conditioned avoidance responses and the percent of learners, was impaired in benzene-exposed rats as compared to control animals. Prenatal exposure to benzene was also followed by reduced retention latency in a step-through passive avoidance task in two retention tests. These results suggest that acute exposure to benzene during gestational organogenesis may cause long-lasting changes in motor behavior and cognitive processes. This may be relevant for the assessment of benzene toxic profile for the progeny of pregnant subjects, although teratogenic effects are not observed. (c) 2006 Elsevier Ireland Ltd. All rights reserved.