The lipophilicity of many organic solvents facilitates their absorption after inhalation or oral or dermal exposure (Bruckner and Warren, 2001). Because of their volatility, the major route of occupational exposure to solvents is inhalation, although dermal exposure can be important in some cases. Once it is absorbed, the disposition and metabolism of a solvent are affected by the route of exposure and by its chemical and physical properties. After ingestion, metabolism and elimination can occur in the first pass through the liver and lungs, before the compound reaches the systemic circulation. Following inhalation exposure most solvents are absorbed rapidly and extensively into the pulmonary and arterial circulation. Some solvents are metabolized to less toxic compounds, others to more toxic compounds or toxic intermediates. Regardless of the route of exposure, unmetabolized lipophilic solvents are distributed predominantly to fatty tissues. Water-soluble solvents, such as alcohols are an exception; they are distributed with body water. Generally, the solvents used in the Gulf War are not highly persistent in the body and are eliminated in a matter of days once exposure ceases.
The central nervous system (CNS) is a major target of organic solvents (Bruckner and Warren, 2001). The CNS-depressing effects of acute, high-dose exposure to solvents are well established in humans and animals, and exposure to most solvents can lead to narcosis if the dose is high enough. In addition, most organic solvents are mucous-membrane irritants and dermal irritants, but only following repeated or prolonged dermal exposure to high concentrations. Permanent CNS damage can occur in humans who chronically abuse solvents, but the effects of low-dose exposure to solvents are less clear. The data on low-dose exposures to solvents come primarily from the epidemiologic literature, which is discussed in the health-outcomes chapters, Chapters 5–9.
In addition to the general chronic solvent-induced CNS effects, some solvents (for example, n-hexane, carbon disulfide, and methyl n-butyl ketone) cause peripheral neuropathy (Graham et al., 1995); symptoms of subchronic and chronic exposure, appear insidiously over weeks to months. The specific solvents known to produce peripheral neuropathy are not believed to have been sent to the Gulf War and are not examined in Chapters 5–9. The clinical features of the neuropathy include sensory loss, distal weakness, and areflexia with a slowing of motor conduction velocity. Nerve biopsy shows axonal degeneration with neurofilamentous axonal swelling and axonal atrophy. Symptoms can progress for months after exposure stops (Huang et al., 1989). In milder cases, symptoms eventually resolve; in more severe cases, residual disability persists over the long term (Arlien-Sobørg, 1992; Feldman, 1998). To judge by the onset and the clinical course, peripheral neuropathy from solvent exposure is a long-term effect. Such peripheral neuropathy was first recognized in humans exposed in the occupational setting and later verified in experimental animals. Peripheral neuropathy is also seen in persons who abuse solvent products containing n-hexane or methyl-n-butyl ketone. N-hexane, carbon disulfide, and methyl-n-butylketone produce identical pathologic and clinical changes. The neurotoxicity of n-hexane and methyl-n-butylketone was found to be mediated by a common