International Agency for Research on Cancer (IARC) - Summaries & Evaluations

(Group 3)

For definition of Groups, see Preamble Evaluation.

VOL.: 65 (1996) (p. 409)

CAS No.: 88-72-2
Chem. Abstr. Name: 1-Methyl-2-nitrobenzene

CAS No.: 99-08-1
Chem. Abstr. Name: 1-Methyl-3-nitrobenzene

CAS No.: 99-99-0
Chem. Abstr. Name: 1-Methyl-4-nitrobenzene

5. Summary of Data Reported and Evaluation

5.1 Exposure data

2-, 3- and 4-Nitrotoluenes are produced commercially, as a mixture, by nitration of toluene. 2- and 4-Nitrotoluenes are used mainly to produce intermediates in the production of colourants. All of these isomers are also used in much smaller quantities in the production of agricultural, pharmaceutical and rubber chemicals. Human exposure to nitrotoluenes can occur during their production and use, although few data are available. Nitrotoluenes have been detected in effluents from the manufacture or use of nitrotoluenes and in surface and groundwater.

5.2 Human carcinogenicity data

No data were available to the Working Group.

5.3 Animal carcinogenicity data

No long-term study of the carcinogenicity of 2-, 3- or 4-nitrotoluene was available to the Working Group.

Rare mesotheliomas of the tunica vaginalis were reported in male rats receiving 2-nitrotoluene in the diet for 13 weeks.

5.4 Other relevant data

No relevant data on absorption, distribution, metabolism or excretion in humans were available to the Working Group.

Urinary elimination is the major route of excretion in rats exposed to nitrotoluene isomers. Male rats excrete more of an administered dose of nitrotoluene in the bile compared with female rats. All three nitrotoluene isomers cause an increase in the incidence of hyaline droplet nephropathy in male rats: the hyaline droplets were associated with 2-globulin. Liver toxicity was observed in rats exposed to 2-nitrotoluene. In mice, the only evidence of toxicity was degeneration and metaplasia of the olfactory epithelium.

In rats, no adverse effect on reproduction or on the offspring was observed following administration of 2-, 3- or 4-nitrotoluene by gavage. All three isomers impaired testicular function and increased the length of the oestrus cycle. The 2-isomer decreased sperm motility in mice.

2-Nitrotoluene was not genotoxic in bacteria, but induced sister chromatid exchange in cultured mammalian cells. In vivo in rats, 2-nitrotoluene bound to macromolecules and, in males, induced unscheduled DNA synthesis in liver cells. In-vivo activity depends on the presence of intestinal bacteria.

3-Nitrotoluene produced a weak induction of sister chromatid exchange, but not of chromosomal aberrations or unscheduled DNA synthesis in mammalian cells in vitro. In vivo, it bound to macromolecules but not to DNA and did not induce unscheduled DNA synthesis.

4-Nitrotoluene was not genotoxic in yeast. In mammalian cells in vitro, it induced sister chromatid exchange and chromosomal aberrations. It did not induce unscheduled DNA synthesis in rat cells exposed either in vitro or in vivo. In vivo in rats, it bound to macromolecules, but not to DNA. It did not induce micronuclei in mouse bone marrow in vivo.

5.5 Evaluation

There is inadequate evidence in humans for the carcinogenicity of nitrotoluenes.

There is limited evidence in experimental animals for the carcinogenicity of 2-nitrotoluene.

There is inadequate evidence in experimental animals for the carcinogenicity of 3- and 4-nitrotoluenes.

Overall evaluation

Nitrotoluenes are not classifiable as to their carcinogenicity to humans (Group 3).

For definition of the italicized terms, see Preamble Evaluation.

Synonyms for 2-nitrotoluene

Synonyms for 3-nitrotoluene

Synonyms for 4-nitrotoluene

Last updated 08/14/1997

    See Also:
       Toxicological Abbreviations