Neurotoxicity of industrial chemicals and contaminants: aspects of biochemical mechanisms and effects.

Nervous system toxicity by industrial chemicals and contaminants cannot be explained by a single mechanism because of the complex functional capacity of the brain and spinal cord. The nervous system is dependent on the adequate supply of oxygen, and therefore, its lack in the ambient air causes rapid dysfunction. Similar effects to hypoxia are caused by agents which reduce oxygen availability at the cellular level by histotoxic mechanisms, e.g., through the inhibition of mitochondrial respiration. Hypoxic effects are rapidly produced, and in cases where a significant number of cells are fatally damaged permanent disability may remain. Acutely harmful effects are also brought about by organic solvents. The typical mode of exposure is that of vapour inhalation. The lipid-soluble molecules pass the blood-brain barrier rapidly and depress the nerve cell membrane functions. This hinders the formation of action potentials. Neuronal cells acquire tolerance towards the membrane-depressant effects in repeated or prolonged exposure so that similar doses do not produce equivalent effects. The development of the tolerance can be regarded as one of the long-term effects of lipophilic chemicals. They may also produce metabolic adaptation so that their biotransformation is enhanced. This may increase the risk of producing more toxic intermediates. The toxic effects thus created can be cumulative since neurons do not multiply by cell division in the postnatal life. The neurotoxicity of metals is more clearly associated with the accumulation of the dose. Adult brain possesses a blood-brain barrier to many water-soluble compounds such that a threshold concentration must be overcome before appreciable toxic effects are seen. Children are in this respect more vulnerable because of their immature barrier function.