Central nervous system toxicity of some common environmental residues in the mouse.

Abstract

To ascertain changes in the level of general central nervous system (CNS) excitability and, therefore, postulated neurotoxicity of some common environmental residues, a bioassay was developed that used a known general CNS stimulant, pentylenetetrazol (PTZ, Metrazol). As a positive control, dieldrin was compared to PTZ and nine other compounds (caffeine, 1,2,3-trichloropropane, ethylene dibromide, Arochlor 1254, pentachlorophenol, heptachlor epoxide, DDT, lindane, and chlordecone) for CNS stimulatory effects, both acutely and subchronically. All doses were administered on an equimole per kilogram basis, rather than milligram per kilogram or %LD50 comparisons. The general level of CNS excitability elicited by each compound relative to the others was assessed. Of the 10 compounds examined, dieldrin showed the most activity in decreasing metrazol-challenge ED50, while chlordecone was most potent in increasing the ED50. Dieldrin, heptachlor epoxide, and chlordecone were shown to potently inhibit PTZ-induced kindling. Of all compounds examined, dieldrin is concluded to have the greatest potential for causing an increase in general CNS excitability, which may relate to persistent behavioral stimulation.