PRINCIPLES OF TOXICOLOGY - Biology East Borneo

374 PROPERTIES AND EFFECTS OF ORGANIC SOLVENTSDepression of Central Nervous System ActivityOne of the common physiological effects which is associated with high levels of exposure to someorganic chemicals, including volatile solvents, is depression of central nervous system (CNS) activity.Chemicals that act as CNS depressants have the capacity to cause general anesthetic effects, inhibitactivity in the brain and the spinal cord, and lower functional capacity, render the individual lesssensitive to external stimuli, and ultimately may result in unconsciousness or death as the most severeconsequence. A general feature of many solvents is their highly lipophilic (“fat-loving”) character. Asdiscussed in Chapter 2, lipophilic chemicals exhibit a high affinity for fats (lipids), coupled with a lowaffinity for water (hydrophobic). Thus, these compounds tend to accumulate in lipid-rich areas of thebody, including lipids in the blood, lipid zones of the nervous system, and depot fats. Neurotoxicchemicals have been shown to accumulate in the lipid membranes of nerve cells after repeatedhigh-level acute exposure or lower-level, chronic exposure, in some cases disrupting normal excitabilityof the nerve tissues and adversely effecting normal nerve impulse conduction.While organic solvents with few or no functional groups are lipophilic and exhibit some limiteddegree of CNS-depressant activity, this property increases with the carbon chain length, to a point.This increased toxicity is most evident when larger functional groups are added to small organiccompounds, since the increase in molecular size generally disproportionately decreases the watersolubility and increases the lipophilicity. As a practical consideration, this observation is relevant onlyto industrial exposures for chemicals up to a five- or six-carbon chain length. As molecular sizeincreases beyond this point for any of the functional classes (amines, alcohols, ethers), the vaporpressure is decreased and the exposure considerations, particularly with regard to inhalation, changedramatically.The unsaturated chemical analogs (organic structures where hydrogens have been deleted, formingone or more double or triple bonds between carbon atoms; see Section 16.3) typically are more potentCNS-depressant chemicals than their saturated (single-bond) counterparts. In a similar fashion, theCNS-depressant properties of an organic compound are generally enhanced by increasing the degreeof halogenation [e.g., chlorine (Cl), bromine (Br)] and, to a lesser extent, by addition of alcoholic(–OH) functional groups. For example, while methane and ethane have no significant anestheticproperties and act as simple asphyxiants at high concentrations, both of the corresponding alcoholanalogs (methanol and ethanol) are potent CNS depressants. Likewise, while methylene chloride (i.e.,dichloromethane, CH 2Cl 2) has appreciable anesthetic properties, chloroform (CHCl 3) is more potentthan methylene chloride, and carbon tetrachloride (CCl 4) is the most potent in terms of anestheticconsiderations.Several solvents have been associated in the literature with behavioral toxicity, including carbondisulfide, styrene, toluene, trichloroethene, and jet fuel, though reports are often difficult to corroborate.Peripheral Nervous SystemA selected group of organic solvents are capable of causing a syndrome known as distal axonalperipheral neuropathy. Among these solvents are n-hexane, methyl n-butyl ketone, and carbondisulfide. The occupation development of the disease condition is slow, but may be accelerated in casesof those guilty of solvent abuse (e.g., inhalation). In at least some cases, the disease state may progressfor 3–4 months after the cessation of exposure.Membrane and Tissue IrritationAnother adverse response of common interest for organic solvents is the potential for membrane andtissue irritation. Because cell membranes are composed principally of a protein–lipid matrix, organicsolvents at sufficient concentrations may act to dissolve that matrix, or extract the fat or lipid portionout of the membrane. This “defatting” process, when applied to skin, may cause irritation and celldamage and, by similar processes, may seriously injure the lungs, or eyes. As described previously,