Table 3.

Major classes of neurotoxicants and their typical exposure sources and neurotoxic action.

Class of toxicant	Typical exposure sources	Typical neurotoxic action	Animal model examples
Metals	Metals are naturally occurring, but human exposure is usually due to current or historical uses. Current sources include mining, smelting, battery manufacturing and recycling, construction, automotive, and electronics.	Toxicity and action vary by metal and dose (e.g., lead is toxic at all levels, whereas copper is essential at low levels and harmful at high). Metals generally harm the CNS by substituting for necessary minerals (e.g., lead substitutes for calcium, which is critical to neuronal signaling), binding to and inactivating necessary enzymes (e.g., arsenic can inactivate $>200$ enzymes), or generating reactive oxygen species.	Prenatal and neonatal lead exposure in mice results in learning deficits and hyperactivity that is attenuated by amphetamine or methylphenidate (Silbergeld and Goldberg 1974, 1975).
Organic solvents	Solvents are used as vehicle and equipment fuels; in almost all chemical and industrial processes; and as ingredients in cleaning and degreasing products, pesticides, paints, adhesives, cosmetics, coatings, and ink.	Toxicity and action vary by solvent and dose, but typically organic solvents are lipophilic and concentrate in lipid-rich brain white matter. Mechanisms of toxicity remain poorly characterized but are related to generation of toxic reactive oxygen species. Consequences can involve dysregulation of glial cells, demyelination of nerve fibers, ischemic damage, and white matter necrosis.	Adult mice acutely exposed to toluene show depressive symptoms as measured by increased time spent immobile during the tail suspension test and forced swim test, which is indicative of despair. These symptoms are not the result of an overall decrease in movement and are reversed via treatment with antidepressants (Yang 2010).
Pesticides	Pesticides are applied in agriculture and manufacturing processes, in parks, golf courses, rights of way, and home and garden use.	Toxicity and action vary by pesticide, but the best-studied classes, organophosphates and carbamate pesticides, inhibit acetylcholinesterase resulting in accumulation of acetylcholine and disrupted neurotransmission in the parasympathetic nervous system.	Young mice (1 month of age) exposed subchronically or chronically to glyphosate demonstrate both depressive and anxiety behaviors including decreased time spent in open arms of an elevated plus maze (Ait Bali 2017).

Note: CNS, central nervous system.