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  • Introduction

  • Is There a Solvent-Induced Chronic Encephalopathy?

  • Solvent Abuse

  • Environmental Contamination

  • Toxicokinetics

    • Absorption

    • Transport and Distribution

    • Elimination

    • Metabolism

    • Physiological Modeling

  • Potentially Sensitive Subpopulations

    • Endogenous Factors

      • Children

      • Elderly

      • Gender

      • Genetics

    • Exogenous Factors

      • P450 Inducers

      • P450 Inhibitors

      • Lifestyle

      • Solvent Mixtures

      • Diseases

  • Chlorinated Hydrocarbons

    • Trichloroethylene

      • Metabolism

      • Modes of Carcinogenic Action in Target Tissues

      • Liver Cancer

      • Lung Cancer

      • Kidney Cancer

      • Cancer Epidemiology Studies

      • Risk Assessment

    • Tetrachloroethylene

      • Metabolism

      • Modes of Cytotoxicity/ Carcinogenicity

      • Hepatorenal Toxicity

      • Cancer Bioassays in Rodents

      • Cancer Epidemiology Studies

      • Risk Assessment

    • 1,1,1-Trichloroethane

      • Toxicokinetics and Metabolism

      • Toxicity

      • Potential Carcinogenicity

      • Methylene Chloride

        • Metabolism

        • Modes of Toxicity/Carcinogenicity

        • Cancer Bioassays in Rodents

        • Cancer Epidemiology Studies

        • Risk Assessment

      • Carbon Tetrachloride

      • Chloroform

  • Aromatic Hydrocarbons

    • Benzene

    • Toluene

    • Xylenes and Ethylbenzene

    • Styrene

  • Alcohols

    • Ethanol

    • Methanol

  • Glycols

    • Ethylene Glycol

    • Diethylene Glycol

    • Propylene Glycol

  • Glycol Ethers

    • Reproductive Toxicity

    • Developmental Toxicity

    • Hematotoxicity

    • Immunotoxicity/Carcinogenicity

  • Fuels and Fuel Additives

    • Automotive Gasoline

    • Methyl tertiary-Butyl Ether

    • Jet Fuel

      • Pulmonary Effects

      • Immune Effects

      • Dermal Effects

  • Carbon Disulfide

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Introduction

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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 such as naphthas and gasoline are complex mixtures, often consisting of hundreds of compounds. Early in the 20th century, there were perhaps a dozen or so known and commonly used solvents. By 1981, this number had climbed to approximately 350 (OSHA, 2006).

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Solvents are classified largely according to molecular structure or functional group. Classes of solvents include aliphatic hydrocarbons, many of which are halogenated (ie, 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 (ie, straight chain, branched chain, or cyclic); (4) whether it is halogenated; and (5) the presence of functional groups. Some class-wide 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, both 1,1,1-trichloroethane (TRI) and 1,1,2-trichloroethylene (TCE) are halocarbons with three chlorine atoms, ...

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