PRINCIPLES OF TOXICOLOGY

16.14 TOXIC PROPERTIES OF REPRESENTATIVE NITROGEN-SUBSTITUTED SOLVENTS 401
Figure 16.27 Aniline.
In the chemical industry, aniline (see Figure 16.27) is a parent substance for the synthesis of many
compounds, including dyes, rubber accelerators, antioxidants, drugs, photographic chemicals, isocyanates,
herbicides, and fungicides.
The most characteristic effect associated with aniline exposure is methemoglobinemia. Because it
is fat-soluble, aniline readily penetrates intact skin and is easily absorbed by inhalation. Moderate
exposure to aniline by any route may cause cyanosis, but as oxygen deficiency increases, associated
symptoms of headache, weakness, irritability, drowsiness, dyspnea, and unconsciousness may occur.
Ingestion of aniline causes splenic enlargement, hemosiderosis, as well as hyperplasia of the bone
marrow. The existence of chronic aniline poisoning is controversial; however, some CNS symptoms
have been reported in association with low dose chronic exposure to aniline. Severe acute toxic effects
may occur at 80 ppm, with symptoms typically appearing at approximately 20 ppm. The most common
symptoms of acute aniline intoxication are cyanosis, lacrimation, tremors, tachypnea, lethargy,
methemoglobinemia, sulfhemoglobinemia, and Heinz body formation. The carcinogenicity of aniline
to humans is not clear, since it was found to be mildly carcinogenic to rats, but was not carcinogenic
to mice. This may be due to interspecies metabolic differences.
Industrially important exposures to aniline may be evaluated by measurements of urinary
p-aminophenol, expressed in the context of urinary creatinine.
Dimethylaniline (see Figure 16.28) is used in the synthesis of dyestuffs, as a solvent, and as an
analytical reagent. This compound can enter a system by inhalation, skin absorption, ingestion, and
eye and skin contact. Signs of intoxication in man are headaches, cyanosis, dizziness, labored
breathing, paralysis, and convulsions. Like aniline, dimethylaniline is readily absorbed through the
skin, with the potential methemoglobinemia. Few reports of industrial exposure are available with
which to estimate the hazards of dimethylaniline. However, cases of severe exposure are accompanied
by visual disturbances and severe abdominal pain. No evidence of reproductive or genetic toxicity is
available for this compound. The TLV ® and PEL have been set at 5 ppm (25 mg/m 3 ) by ACGIH and
OSHA, respectively.
Benzidine (see Figure 16.29) principally is used in the synthesis of dyes, but may also be used as
a hardener for rubber, and as a laboratory reagent. A high incidence of bladder cancer has been reported
among workers who have been exposed to benzidine. Inhalation and skin absorption are significant
routes for benzidine exposure which may result in contact dermatitis. Benzidine is a known human
Figure 16.28 Dimethylaniline.