PRINCIPLES OF TOXICOLOGY - Biology East Borneo

378 PROPERTIES AND EFFECTS OF ORGANIC SOLVENTSattention in this context because their low surface tension allows them to spread over a large surfacearea, thereby having the potential to produce damage to the lungs after exposure to relatively smallquantities. These chemicals may sensitize the heart to epinephrine (adrenaline), but that feature is rarelya practical consideration since a narrow dose range typically separates cardiac sensitization from fatalnarcosis.The chronic exposure to some aliphatics, notably hexane and heptane, reportedly has the capacityto produce polyneuropathy in humans and animals, characterized by a lowered nerve conductionvelocity and a “dying back” type of degenerative change in distal neurons. Symptoms of this conditionmay include muscle pain and spasms, muscular weakness, and paresthesias (tingling or numbness).Normal metabolites have been implicated as the causative agents in this case, with 2,5-hexanedioneand 2,6-heptanedione as the respective toxic metabolites of hexane and heptane. Since these metabolitesrepresent oxidative breakdown products, first to the alcohol and then to the respective diketone,it has been suggested and observed that structurally similar alcohols and ketones at sufficientconcentration may produce similar neuropathies compared to the parent aliphatic hydrocarbons.The alkanes generally are not considered to have carcinogenic potential.Unsaturated Aliphatic Solvents: C n H 2nOlefins (Alkenes)Alkenes, which are the double-bonded structured analogs of the alkanes, also are referred to as olefins,and generally exhibit qualitative toxicological properties similar to those of the alkanes.The double bond typically enhance(s) the irritant and CNS-depressant properties in comparison tothe alkanes, but this enhancement often is of limited practical significance. For example, ethylene is amore potent anesthetic than its corresponding alkane (ethane), which acts as a simple asphyxiant.However, since a concentration greater than 50 percent ethylene is required to induce anesthesia, thepotential for hypoxia and the explosive hazard are major drawbacks that preclude its clinical use as ananesthetic. Such an ethylene concentration in an industrial setting would sufficiently displace theoxygen present so that asphyxiation (as is the case with ethane) would be the major concern, ratherthan narcosis and respiratory arrest. Of greater toxicological interest is the observation that theunsaturated nature of the hexene and heptene series apparently largely abolishes the neurotoxic effectsthat have been reported following chronic hexane or heptane exposure. This change may be related tosubstantive metabolic differences between the groups.16.4 TOXIC PROPERTIES OF REPRESENTATIVE ALICYCLIC SOLVENTSAlicyclic hydrocarbons functionally may be viewed as alkane chains of which the ends have beenjoined to form a cyclic, or ring, structure (see, e.g., structures in Figure 16.1). Their toxicologicalproperties resemble those of their open-chain relatives and they generally exhibit anesthetic orCNS-depressant properties at high exposure concentrations. Industrial experience indicates thatnegligible chronic effects typically are associated with long term exposure to these compounds. Thelower-molecular-weight alicyclics (e.g., cyclopropane) received some limited attention as surgicalanesthetics, but the larger compounds (e.g., cyclohexane) are not as useful because the incrementalFigure 16.1 Cyclopropane and cyclobutane.