PRINCIPLES OF TOXICOLOGY

16.5 TOXIC PROPERTIES OF REPRESENTATIVE AROMATIC HYDROCARBON SOLVENTS 379
difference between narcosis and a lethal concentration is small. While there are qualitative similarities
between the groups, the irritant qualities of cycloalkenes (cycloolefins) tend to be of greater concern
than those of the unsaturated analogs.
16.5 TOXIC PROPERTIES OF REPRESENTATIVE AROMATIC HYDROCARBON
SOLVENTS
The class of organic solvents that commonly are referred to as “aromatics” are composed of one or
more six-carbon (phenyl) rings. The simplest member of the class (defined by lowest molecular weight)
is the single-ringed analog termed benzene, followed by the aliphatic-substituted phenyl compounds
(alkylbenzenes) and then the aryl- and alicyclic-substituted, multiring benzenes. Diphenyl and
polyphenyl compounds are represented in this class, which includes the polynuclear aromatic hydrocarbons
(PNAs or PAHs), such as naphthalene, which are common as constituents of petroleum fuels,
as well as other commercial products. Benzene and its alkyl relatives are important industrial
compounds, with over 1.5 billion gallons of benzene annually produced or imported in the United
States. Even larger quantities of several of the alkylbenzenes (e.g., toluene, xylenes) are produced.
Benzene and the alkylbenzenes are common as raw materials and solvents in the ink, dye, oil, paint,
plastics, rubber, adhesives, chemical, drug, and petroleum industries. Most commercial motor gasolines
contain at least 1 percent benzene, a value which may range up to several percent, and
alkylbenzenes may be present in or may be added to unleaded fuels to concentrations reaching 25–35
percent of the total commercial product.
Aromatic hydrocarbons typically cause more tissue irritation than the corresponding molecular
weight aliphatics or alicyclics. These phenyl compounds may cause primary dermatitis and defatting
of the skin, resulting in tissue injury or chemical burns if dermal contact is repetitive or prolonged.
Conjunctivitis and corneal burns have been reported when benzene or its alkyl derivatives are splashed
into the eyes, and naphthalene has been reported to cause cataracts in animals at high dosages. If the
aromatics are reaspirated into the lungs after ingestion (e.g., following vomiting), they are capable of
causing pulmonary edema, chemical pneumonitis, and hemorrhage. Inhalation of high concentrations
can result in conditions ranging from bronchial irritation, cough, and hoarseness to pulmonary edema.
Once absorbed and in systemic circulation, these hydrocarbons are demonstrably more toxic than
aliphatics and alicyclics of comparable molecular weight. While CNS depression is a major acute effect
of this class of compounds, its severe form differs fundamentally from that observed following
exposure to the aliphatics. The aliphatic-induced anesthesia and coma is characterized by an inhibition
of deep tendon reflexes. In comparison, aromatic-induced unconsciousness and coma is characterized
by motor restlessness, tremors, and hyperactive reflexes, sometimes preceded by convulsions.
Representative members of the aromatic hydrocarbon family are profiled in the following section
(see, e.g., benzene structure in Figure 16.2).
Benzene is a colorless liquid with a characteristic odor that generally is described as pleasant or
balsamic. The term benzene should not be confused with benzine, as the latter historically refers to a
mixed-component, low-boiling-range, petroleum fraction composed primarily of aliphatic hydrocarbons.
Because of its extensive use for many years, this compound has been studied perhaps more
extensively than any other. Benzene can be toxic by all routes of administration at sufficient dosage;
however, the acute inhalation LC 50 in animals begins at about 10,000 ppm. This may be compared
Figure 16.2 Benzene.