Toxicity Profiles
Condensed Toxicity Summary for NITROBENZENE
NOTE: Although the toxicity values presented in these toxicity profiles were correct at the time they were produced, these values are subject to change. Users should always refer to the Toxicity Value Database for the current toxicity values.
MARCH 1993
Prepared by: Rosmarie A. Faust, Ph.D., Chemical Hazard Evaluation Group, Biomedical Environmental Information Analysis Section, Health and Safety Research Division, *, Oak Ridge, Tennessee
Prepared for: Oak Ridge Reservation Environmental Restoration Program.
*Managed by Martin Marietta Energy Systems, Inc., for the U.S. Department of Energy under Contract No. DE-AC05-84OR21400.
Nitrobenzene (CAS Reg. No. 98-95-3) is a pale yellow liquid with an odor of bitter almonds (Dunlap, 1981). Most of the nitrobenzene produced is used as an intermediate in the synthesis of aniline. An anthropogenic environmental contaminant, nitrobenzene can be released to wastewater and air from industrial sources (ATSDR, 1990). It is primarily removed from the environment by photolysis, reaction with hydroxyl radicals, volatilization, and biodegradation (U.S. EPA, 1985).
Nitrobenzene can be absorbed by humans following oral, inhalation, or dermal exposure (U.S. EPA, 1980). When absorbed into the blood, nitrobenzene oxidizes the iron in hemoglobin to form methemoglobin, thus decreasing the oxygen carrying capacity of the blood. The primary systemic effect associated with human exposure to nitrobenzene is methemoglobinemia. Acute oral exposure has resulted in methemoglobinemia, cyanosis, and anemia, and neurological effects, including headache, nausea, vertigo, confusion, unconsciousness, apnea, coma, and death (Piotrowski, 1967; U.S. EPA, 1980; ATSDR, 1990). Methemoglobinemia has also been reported following subchronic to chronic occupational exposure to nitrobenzene. Additional effects included sulfhemoglobinemia, presence of Heinz bodies in erythrocytes, liver toxicity (hepatomegaly, jaundice, and altered serum chemistry), spleen enlargement, and neurological symptoms (headache, nausea, weakness, vertigo, numbness of legs, and hyperalgesia of hands and feet) (U.S. EPA, 1980; Ikeda and Kita, 1964). Dermal exposure to nitrobenzene has resulted in contact dermatitis (Beauchamp et al., 1982).
Effects observed in subchronic inhalation studies with rodents exposed to nitrobenzene at concentrations up to 50 ppm for 90 days included methemoglobinemia, splenic lesions (splenomegaly, increased hemosiderosis and hematopoiesis), liver toxicity (hepatocyte hyperplasia and focal necrosis), kidney nephrosis, and testicular degeneration. Morphologic changes of the adrenal cortex were reported for mice (CIIT, 1984). Effects on the spleen, kidneys, and liver were also reported in rodents exposed to concentrations up to 125 ppm for 14 days. In addition, there was morphologic damage to the hind brain (Medinsky and Irons, 1985). Testicular degeneration and decreased sperm levels were reported in a two-generation reproductive study with rats (Dodd et al., 1987).
A reference dose (RfD) of 5E-3 mg/kg/day for subchronic oral exposure and 5E-4 mg/kg/day for chronic oral exposure to nitrobenzene was calculated from a lowest-observed-adverse-effect level (LOAEL) of 25 mg/m3 derived from a 90-day inhalation study with F344 rats and B6C3F1 mice (CIIT, 1984). The critical effects were hematological changes in F344 rats, and adrenal, renal, and hepatic lesions in B6C3F1 mice (U.S. EPA, 1992a,b). Because this value is based on a route to route extrapolation, the RfD may change pending further review by EPA (U.S. EPA, 1992a). The same study (CIIT, 1984) served as the basis of a reference concentration (RfC) of 2E-2 mg/m3 for subchronic inhalation exposure and 2E-03 mg/m3 for chronic inhalation exposure to nitrobenzene (U.S. EPA, 1992b). This value is currently under review by an EPA work group (U.S. EPA, 1992a).
No suitable cancer bioassays or epidemiological studies are available to assess the carcinogenicity of nitrobenzene. Therefore, U.S. EPA (1992a,b) has placed nitrobenzene in weight-of-evidence group D, not classifiable as to human carcinogenicity.
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Last Updated 8/29/97