Toxic chemicals and natural products in the environment contribute to the burden of neurological disease. For this reason, research on environmental neurotoxins can increase our ability to identify and control preventable causes of these often incurable diseases. Several reviews have catalogued lists of chemicals and agents associated with human neurotoxicity, including solvents, metals, pesticides, and natural toxins of marine origin (OTA, 1990; NRC, 1992; IOM, 1991; Morris, 1999). Many toxic chemicals in the workplace, especially solvents and narcotizing agents, are regulated on the basis of their neurotoxic effects (OTA, 1990). Many biocides, including insecticides, fungicides, and rodenticides were deliberately designed to be neurotoxic to pest organisms (OTA, 1990). However, target sites in the nervous system are largely conserved across species, and desirable lethal effects in pests may engender undesirable neurotoxicity in humans.

The effects of both acute and chronic exposures to many neurotoxins have been well studied. However, there is at present considerable uncertainty about the role of neurotoxins in the long latency neurodegenerative diseases, such as Parkinsonism, dementia or progressive neuropathies. Recent epidemiological studies strongly suggest associations between certain pesticides and increased risks of Parkinsonism, and between chronic exposures to certain solvents and dementias of the non-Alzheimer type (Feldman, 1999). Detecting chemical etiologies of these neurological diseases is difficult, for two reasons: epidemiological resources and data on patterns of neurological disease incidence and prevalence are very limited, and there are few animal models of acquired neurological disease.

In this chapter, we discuss examples of neurotoxic agents associated with human disease and neurological impairments. We have selected examples that illustrate the importance of understanding differences in the effects of high dose acute exposures from the effects of low dose chronic exposures. In addition, for many neurotoxins the route of exposure and the age or developmental stage of the exposed individual determines the type of neurotoxic insult. In some cases, toxic agents by themselves damage the nervous system, while in other cases, these agents probably interact with host susceptibility factors, including genetics, to induce disease or to hasten the onset or increase the severity of disease.

Lead

The heavy metal lead may be the single most significant cause of neurotoxicity in human populations worldwide.