The toxicity to rat cerebral cortex or topical applications of acetaldehyde, ammonia or bilirubin.

The relative toxicity of acetaldehyde, ammonia and bilirubin to cerebral cortex of rats has been tested by superfusion of the intact dura for 1 h with each toxin separately. The cortex was examined histologically after 6 days survival using a silver strain which selectively impregnates degenerating axons and their synaptic terminals. A tissue concentration of 30 mM acetaldehyde was found to cause axonal and terminal degeneration, whereas 11 mM acetaldehyde was not toxic, and did not produce any structural changes detectable by electron microscopy. In terms of tissue concentrations, acetaldehyde was at least 27 times more toxic than ethanol on a molar basis. However, the acetaldehyde concentration necessary to produce neuronal degeneration in a 1 h exposure is many times greater than ever reported in CSF in human alcoholism. Both ammonia and bilirubin are capable of causing neuronal degeneration, but we have not measured the tissue concentrations that are toxic. Comparison of molar concentrations in the superfusing fluids showed that ammonia is at least 39 times more toxic than acetaldehyde, and at least 1000 times more toxic than ethanol. Superfusion with an ethanolic solution of bilirubin (2.5mM) was strongly toxic, but this solution diluted to 50% with saline was not toxic. The possibility exists that ammonia or bilirubin may reach concentrations toxic to neurons in alcoholism, especially in the presence of liver damage.