PRINCIPLES OF TOXICOLOGY - Biology East Borneo

16.5 TOXIC PROPERTIES OF REPRESENTATIVE AROMATIC HYDROCARBON SOLVENTS 379difference between narcosis and a lethal concentration is small. While there are qualitative similaritiesbetween the groups, the irritant qualities of cycloalkenes (cycloolefins) tend to be of greater concernthan those of the unsaturated analogs.16.5 TOXIC PROPERTIES OF REPRESENTATIVE AROMATIC HYDROCARBONSOLVENTSThe class of organic solvents that commonly are referred to as “aromatics” are composed of one ormore 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 andpolyphenyl 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 industrialcompounds, with over 1.5 billion gallons of benzene annually produced or imported in the UnitedStates. 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 gasolinescontain at least 1 percent benzene, a value which may range up to several percent, andalkylbenzenes may be present in or may be added to unleaded fuels to concentrations reaching 25–35percent of the total commercial product.Aromatic hydrocarbons typically cause more tissue irritation than the corresponding molecularweight aliphatics or alicyclics. These phenyl compounds may cause primary dermatitis and defattingof 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 splashedinto the eyes, and naphthalene has been reported to cause cataracts in animals at high dosages. If thearomatics are reaspirated into the lungs after ingestion (e.g., following vomiting), they are capable ofcausing pulmonary edema, chemical pneumonitis, and hemorrhage. Inhalation of high concentrationscan 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 thanaliphatics and alicyclics of comparable molecular weight. While CNS depression is a major acute effectof this class of compounds, its severe form differs fundamentally from that observed followingexposure to the aliphatics. The aliphatic-induced anesthesia and coma is characterized by an inhibitionof deep tendon reflexes. In comparison, aromatic-induced unconsciousness and coma is characterizedby 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 orbalsamic. The term benzene should not be confused with benzine, as the latter historically refers to amixed-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 moreextensively than any other. Benzene can be toxic by all routes of administration at sufficient dosage;however, the acute inhalation LC 50in animals begins at about 10,000 ppm. This may be comparedFigure 16.2 Benzene.