PRINCIPLES OF TOXICOLOGY

observed are dermatitis, anemia, heart irregularities, and peripheral neuritis. Persons deficient in
glucose 6-phosphate dehydrogenase are sensitive to hemolytic anemia. Some of these compounds
cause bladder tumors as well. Again, the specific toxicities of any individual member of this class of
compounds should be reviewed individually if it is to be used.
Aliphatic and Alicyclic Nitro Compounds and Related Substances
The aliphatic/alicyclic nitro compounds generally are oily liquids that exhibit low solubility and low
volatility. They are of limited industrial significance, but several members have important uses as
specialized fuels and as strong solvents. The nitro paraffins are acidic compounds and thus are rapidly
neutralized with strong bases and readily titrated. Its tautomerism forms the basis for its ability to be
easily chlorinated and form chloronitroparaffins such as trichloronitromethane. These compounds are
moderate skin and mucous membrane irritants, particularly the halogenated derivatives. Saturated
members of this class are not well absorbed, while unsaturated members exhibit significant dermal
absorption.
Nitromethane (see Figure 16.31) and other nitroparaffins are synthesized by the vapor-phase
nitration of propane. Nitromethane may be used as rocket fuel, a gasoline additive, a solvent for
cellulosic compounds, polymers and waxes, and in chemical synthesis.
Nitromethane, like other nitroparaffins, may produce narcosis, methemoglobinemia, mucus membrane
irritation, CNS excitation, and liver damage. However, based on periodic physical examinations
of plant operators engaged in the manufacture and handling of nitromethane for several years, no
chronic effects have been attributed to this compound. Nitromethane has not exhibited significant
mutagenic capacity in tests performed with Salmonella typhimurium. The TLV ® and PEL values which
have been established by ACGIH and OSHA for nitromethane are 20 and 100 ppm, respectively.
Aromatic Nitro Compounds
16.15 TOXIC PROPERTIES 403
The aromatic nitro compounds are formed by substituting a nitro group directly on the benzene ring.
In general, aromatic nitro compounds produce dermal sensitization, CNS depression, and methemoglobinemia.
These compounds can have the capacity to uncouple oxidative phosphorylation and to
produce liver injury. Other reported adverse effects include dermatitis, anemia, cardiac irregularities,
peripheral neuritis, and bladder tumors. Persons deficient in glucose-6-phosphate dehydrogenase are
demonstrably sensitive to hemolytic anemia as well.
Nitrobenzene (see Figure 16.32) is used as a solvent intermediate in the preparation of aniline,
benzidine, and other chemicals, in shoe and metal polishes, and as a solvent. The vapor is readily
absorbed through the skin and lungs. Following absorption nitrobenzene undergoes transformations
into its metabolites, which consist of p-aminophenol, p-hydrooxacetanilide sulfate, p-nitrophenol
sulfate, and m-nitrophenol sulfate. Ring hydroxylation and reduction are important steps in the
biotransformation of nitrobenzene, and the resulting metabolites are excreted mainly in the urine.
The primary toxic effect of nitrobenzene involves methemoglobin formation, although the method
by which nitrobenzene causes this condition is not well understood. The primary opinion is that heme
iron is oxidized by the oxidation-reduction cycling of the metabolites. In subacute and chronic forms
of poisoning, hemolysis causes anemia as the main symptom, but other symptoms such as headache,
Figure 16.31 Nitromethane.