Neuroelectrical disturbance as indicator of chronic chlordane toxicity

Abstract

Adult male rats equipped with chronically implanted electrodes were treated with chlordane ip to examine its influence on spontaneous electrocortical activity. Injections of 350 mg/kg resulted in characteristic signs of organochlorine poisoning, culminating in death within 1 hr. Neurotoxic effects of lethal exposure were seen as high-amplitude episodes (400–630 μV) with secondary respiratory waves leading to isoelectric tracings; respiratory depression was therefore implicated in chlordane-induced mortality. EEGs monitored from unanesthetized rats subjected to daily, low-level injections (0.15, 1.75, and 25.0 mg/kg) revealed dose-dependent alterations of brain potentials without behavioral signs of chronic toxicity. Mean spontaneous activity from all montages was significantly increased after 42 days (47–80% above predosage and control values.) Changes included a progressive shift toward fast beta rhythms (>25 Hz), reduction of delta (0.5-3 Hz) and theta (4–7 Hz) frequencies, elevation of amplitude, and replacement of sinusoidal waves by sharp, complex discharges. These changes were directly related to length of exposure, thus implying that chlordane is a cumulative neurotoxin. Starvation and concurrent chlordane treatment interacted synergistically to produce abnormal high-voltage potentials suggestive of lethal cerebral patterns. We interpreted appearance of these slow-wave spikes as evidence of chlordane mobilization from storage depots and subsequent neuroconcentration. Removal of chlordane failed to stimulate recovery of the EEG. Instead, significant deviations from controls continued after 60 days withdrawal. It may be concluded, therefore, that chlordane is a persistent neurotoxin and that electrocerebral disturbance is an early and sensitive indicator of chlordane intoxication.