For definition of Groups, see Preamble Evaluation.
Vol.: 65 (1996) (p. 381)
CAS No.:
Chem. Abstr. Name: Nitrobenzene
5.1 Exposure data
Nitrobenzene has been produced commercially since the early nineteenth century by nitration of benzene. It is a major chemical intermediate used mainly in the production of aniline, itself a major chemical intermediate in the production of dyes. Human exposure may occur both by inhalation and by skin absorption during its production and use. Nitrobenzene has been detected in surface and groundwater.
5.2 Human carcinogenicity data
No data were available to the Working Group.
5.3 Animal carcinogenicity data
Nitrobenzene was tested by inhalation exposure in one study in mice and in two studies in rats. In mice, the incidences of alveolar-bronchiolar neoplasms and thyroid follicular-cell adenomas were increased in males. In one study in rats, the incidences of hepatocellular neoplasms, thyroid follicular-cell adenomas and adenocarcinomas and renal tubular-cell adenomas were increased in treated males. In treated females, the incidences of hepatocellular neoplasms and endometrial stromal polyps were increased. In a study using male rats only, the incidence of hepatocellular neoplasms was increased.
5.4 Other relevant data
In humans, nitrobenzene is readily absorbed by inhalation. Penetration through the skin also occurs. A major part of the absorbed dose is excreted into the urine: 10-20% of the dose is excreted as 4-nitrophenol, the concentration of which may be used for biological monitoring. A smaller fraction is excreted as 4-aminophenol. The elimination kinetics contains at least two compartments, the first with a half-life of hours and the second with a half-life of days.
In rodents and rabbits, 4-nitrophenol and 4-aminophenol are major urinary metabolites.
There is limited information on the toxic effects of exposure to nitrobenzene in humans. However, it is clear that both accidental ingestion and occupational exposure may cause methaemoglobinaemia, haemolytic anaemia and toxic hepatitis.
Following inhalation of nitrobenzene, liver, lung and splenic toxicity is observed in both rats and mice, although mice appear to be more sensitive than rats to the toxic effects of this chemical. Methaemoglobinaemia and anaemia are also observed in both rats and mice.
In female rats, no teratogenic or reproductive effect of exposure to nitrobenzene was observed. Testicular atrophy has been observed in rats. In a two-generation reproduction study in rats, a decrease in the fertility index of the F0 and F1 generations occurred. No teratogenic effect has been observed in rabbits.
Nitrobenzene was non-genotoxic in bacteria and mammalian cells in vitro. In mammals in vivo, it was inactive.
5.5 Evaluation
There is inadequate evidence in humans for the carcinogenicity of nitrobenzene.
There is sufficient evidence in experimental animals for the carcinogenicity of nitrobenzene.
Overall evaluation
Nitrobenzene is possibly carcinogenic to humans (Group 2B).
For definition of the italicized terms, see Preamble Evaluation.
Synonyms
See Also:
Toxicological Abbreviations
Nitrobenzene (EHC 230, 2003)
Nitrobenzene (ICSC)