The environmental pollutant endosulfan disrupts cerebral cortical function at low doses

Endosulfan can induce convulsions that could lead to brain damage. The variability and lack of specificity of neurological signs and symptoms in the pre-convulsive stages makes early diagnosis difficult. We sought to determine if electrophysiological exploration of the cerebral cortex could yield objective signs of endosulfan intoxication at levels that do not elicit convulsions. Endosulfan was administered intravenously to Sprague-Dawley adult rats under urethane anesthesia at doses from 0.5 to 4mg/kg. EEG power and the evoked potentials (EP) to forepaw electrical stimulation were studied over the contralateral (S1CL) and homolateral (S1HL) cortical somatosensory areas and the contralateral visual area (V1CL). At each area, five EP waves were measured. Arterial blood pressure, heart rate and body temperature were also recorded. Endosulfan induced a dose-related increase in EPs at all sites. At S1CL, EP peak amplitude was greater than baseline at 1, 2 and 4mg/kg for the first negative, second positive and third negative waves, and at 2 and 4mg/kg for the first and third positive waves. Similar but less marked trends were observed at S1HL and V1CL. A shift of EEG power to higher frequencies (alpha and beta EEG bands) was only present at 4mg/kg. In conclusion, endosulfan induced a large increase of cortical evoked potentials amplitudes at doses that did not elicit convulsions. These responses could be used as a non-invasive diagnostic tool to detect low-level endosulfan intoxication in humans and to help establish the NOAEL and LOAEL levels of this pollutant.