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INTRODUCTION

The term solvent refers to a class of organic chemicals of variable lipophilicity and volatility. These properties, coupled with small molecular size and lack of charge, make inhalation the major route of exposure and provide for ready absorption across membranes of the lung, gastrointestinal (GI) tract, and skin. In general, the lipophilicity of solvents increases with increasing numbers of carbon and/or halogen atoms, while volatility decreases. Organic solvents are frequently used to dissolve, dilute, or disperse materials that are insoluble in water. As such they are widely employed as degreasers and as constituents of paints, varnishes, lacquers, inks, aerosol spray products, dyes, and adhesives. Other uses are as intermediates in chemical synthesis, and as fuels and fuel additives. Most organic solvents are refined from petroleum. Many solvents such as naphthas and gasoline are complex mixtures, often consisting of hundreds of compounds. Early in the twentieth century, there were perhaps a dozen or so known and commonly used solvents. By 1981, this number had climbed to approximately 350 (OSHA, 2006).

Solvents are classified largely according to molecular structure or functional group. Classes of solvents include aliphatic hydrocarbons, many of which are halogenated (i.e., halocarbons); aromatic hydrocarbons; alcohols; ethers; esters/acetates; amides/amines; aldehydes; ketones; and complex mixtures that defy classification. The main determinants of a solvent's inherent toxicity are: (1) its number of carbon atoms; (2) whether it is saturated or has double or triple bonds between adjacent carbon atoms; (3) its configuration (i.e., straight chain, branched chain, or cyclic); (4) whether it is halogenated; and (5) the presence of functional groups. Some class-wise generalizations regarding toxicity can be made. For example, the more lipophilic a hydrocarbon, the more potent a central nervous system (CNS) depressant it is; amides/amines tend to be potent sensitizers; aldehydes are particularly irritating; hydrocarbons that are extensively metabolized tend to be more cytotoxic/mutagenic; and many unsaturated, short-chain halocarbons are animal carcinogens. The toxicity of solvents within the same class can vary dramatically. For example, 1,1,1-trichloroethane (TRI) and 1,1,2-trichloroethylene (TCE) are both halocarbons with three chlorine atoms, yet unsaturated TCE is carcinogenic in the rat and mouse, but TRI is not. Similar results have been reported for 2,4- and 2,6-diaminotoluene in rodents, as only the 2,4-isomer is capable of inducing significant hepatocyte proliferation and liver tumors. Slight structural differences in solvent metabolites are also of toxicological consequence. The peripheral neuropathy induced by n-hexane and 2-hexanone is dependent on the production of the γ-diketone metabolite 2,5-hexanedione. Diketones lacking the gamma structure are not neurotoxic. Thus, subtle differences in chemical structure can translate into dramatic differences in toxicity.

Nearly everyone is exposed to solvents during their normal activities. Consider, for example, a person who works in an aircraft factory as a metal degreaser (TCE exposure) drives to the neighborhood bar after work and has a few drinks (ethanol exposure) and cigarettes (benzene and styrene exposure); stops on the way home at a self-service filling ...

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