PRINCIPLES OF TOXICOLOGY

378 PROPERTIES AND EFFECTS OF ORGANIC SOLVENTS
attention in this context because their low surface tension allows them to spread over a large surface
area, thereby having the potential to produce damage to the lungs after exposure to relatively small
quantities. These chemicals may sensitize the heart to epinephrine (adrenaline), but that feature is rarely
a practical consideration since a narrow dose range typically separates cardiac sensitization from fatal
narcosis.
The chronic exposure to some aliphatics, notably hexane and heptane, reportedly has the capacity
to produce polyneuropathy in humans and animals, characterized by a lowered nerve conduction
velocity and a “dying back” type of degenerative change in distal neurons. Symptoms of this condition
may 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-hexanedione
and 2,6-heptanedione as the respective toxic metabolites of hexane and heptane. Since these metabolites
represent 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 sufficient
concentration may produce similar neuropathies compared to the parent aliphatic hydrocarbons.
The alkanes generally are not considered to have carcinogenic potential.
Unsaturated Aliphatic Solvents: CnH2n
Olefins (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 to
the alkanes, but this enhancement often is of limited practical significance. For example, ethylene is a
more 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, the
potential for hypoxia and the explosive hazard are major drawbacks that preclude its clinical use as an
anesthetic. Such an ethylene concentration in an industrial setting would sufficiently displace the
oxygen present so that asphyxiation (as is the case with ethane) would be the major concern, rather
than narcosis and respiratory arrest. Of greater toxicological interest is the observation that the
unsaturated nature of the hexene and heptene series apparently largely abolishes the neurotoxic effects
that have been reported following chronic hexane or heptane exposure. This change may be related to
substantive metabolic differences between the groups.
16.4 TOXIC PROPERTIES OF REPRESENTATIVE ALICYCLIC SOLVENTS
Alicyclic hydrocarbons functionally may be viewed as alkane chains of which the ends have been
joined to form a cyclic, or ring, structure (see, e.g., structures in Figure 16.1). Their toxicological
properties resemble those of their open-chain relatives and they generally exhibit anesthetic or
CNS-depressant properties at high exposure concentrations. Industrial experience indicates that
negligible chronic effects typically are associated with long term exposure to these compounds. The
lower-molecular-weight alicyclics (e.g., cyclopropane) received some limited attention as surgical
anesthetics, but the larger compounds (e.g., cyclohexane) are not as useful because the incremental
Figure 16.1 Cyclopropane and cyclobutane.