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

2-CHLORONITROBENZENE, 3-CHLORONITROBENZENE
AND 4-CHLORONITROBENZENE
(Group 3)

For definition of Groups, see Preamble Evaluation.

VOL.: 65 (1996) (p. 263)

CAS No.: 88-73-3
Chem. Abstr. No.: 1-Chloro-2-nitrobenzene

CAS No.: 121-73-3
Chem. Abstr. No.: 1-Chloro-3-nitrobenzene

CAS No.: 100-00-5
Chem. Abstr. No.: 1-Chloro-4-nitrobenzene

5. Summary of Data Reported and Evaluation

5.1 Exposure data

2-, 3- and 4-Chloronitrobenzenes are produced as a mixture by nitration of chlorobenzene. After separation, the three isomers are used as important chemical intermediates in the production of colourants, pharmaceuticals and a variety of other products. Human exposure to chloronitrobenzenes may occur during the production and use of these intermediates.

5.2 Human carcinogenicity data

No data on the carcinogenicity of 2-, 3- or 4-chloronitrobenzene to humans were available to the Working Group.

5.3 Animal carcinogenicity data

2-Chloronitrobenzene was tested for carcinogenicity by oral administration in the diet in one study in mice and in one study in rats. The studies were inadequate for an evaluation. 4-Chloronitrobenzene was tested for carcinogenicity by oral administration in the diet in one study in mice and in one study in rats. Although the study in mice reported an increased incidence of vascular tumours in exposed males and females, neither study was considered adequate for an evaluation. 3-Chloronitrobenzene has not been tested for carcinogenicity in experimental animals.

5.4 Other relevant data

4-Chloronitrobenzene is absorbed through inhalation and/or via the skin upon human exposure after which urinary metabolites of 4-chloronitrobenzene appear, which are the results of N-acetylation, nitro-group reduction and — to a lesser extent — ring-hydroxylation. Metabolism is slow, with elimination of metabolites occurring over many days. Considerable interindividual variation occurs in this metabolism.

The urinary metabolites of 4-chloronitrobenzene are qualitatively similar in humans and rats.

No data concerning the absorption, distribution, metabolism and excretion or toxic effects of 2- or 3-chloronitrobenzene in humans were available to the Working Group.

The disposition of 2-chloronitrobenzene in rats is similar to that of 4-chloronitrobenzene.

In humans, exposure to 4-chloronitrobenzene is associated with such symptoms as headache, palpitation, dizziness, nausea, vomiting and poor appetite. Cyanosis, methaemoglobinaemia and anaemia also occur. Methaemoglobinaemia and anaemia occur in rats exposed to 4-chloronitrobenzene, 3- chloronitrobenzene or 2- chloronitrobenzene.

In a single study in rats, a maternally toxic dose of 4-chloronitrobenzene increased the resorption rate and the frequency of skeletal malformations. In female rats and mice, inhalation exposure to 4-chloronitrobenzene increased the oestrus cycle length. In rats, but not mice, inhalation exposure to the compound decreased spermatogenesis with atrophy of the seminiferous tubules. In a continuous breeding study, a progressive decrease in fertility was noted in mice receiving 4-chloronitrobenzene.

In rats and mice exposed to 2-chloronitrobenzene by inhalation, decreased spermatogenesis was observed. No significant change was observed in exposed females. In a continuous breeding study, fertility was not affected in mice receiving 2-chloronitrobenzene.

2-Chloronitrobenzene induced reverse mutations but not primary DNA damage in bacteria. It was not mutagenic to insects. In mammalian cells in vitro, it induced sister chromatid exchange and chromosomal aberrations. Intraperitoneal injection into mice resulted in DNA damage in the liver, kidney and brain.

3-Chloronitrobenzene gave negative results in bacterial mutagenicity assays and in cultured mammalian cell chromosomal assays.

4-Chloronitrobenzene induced reverse mutations but not primary DNA damage in bacteria. It was not mutagenic to insects. At toxic doses, it induced chromosomal aberrations, sister chromatid exchange and repairable DNA breaks in cultured mammalian cells. Intraperitoneal injection into mice induced DNA damage in the liver, kidney and brain.

5.5 Evaluation

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

There is inadequate evidence in experimental animals for the carcinogenicity of chloronitrobenzenes.

Overall evaluation

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

For definition of the italicized terms, see Preamble Evaluation

Synonyms for 2-Chloronitrobenzene

Synonyms for 3-Chloronitrobenzene

Synonyms for 4-Chloronitrobenzene


Last updated 08/14/1997






















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       Toxicological Abbreviations