1-chloro-2-nitrobenzene

Endpoint summary

Additional information

1-Chloro-2-nitrobenzene, under appropriate conditions of exposure, is absorbed by the body both via the skin and the gastrointestinal tract as well as via the respiratory tract. Rat studies with labelled chemical show that 1-chloro-2-nitrobenzene absorption is 80 % following oral administration and at least 40 % after open dermal application. 0n 11 consecutive days, 65 mg 1- chloro-2-nitrobenzene/kg bw was administered by gavage to adult and to old rats. On d 1, 5, and 9 applied substance was labelled and urine and faeces were collected in the following 96 hours. The adult rats excreted 71-74 % of the dose in the urine and 20-27 % of the dose in the faeces. Excretion rate increased with the duration of treatment. Urinary excretion rate in the old rats consisted 71-85 % of the dose and did not increase with the duration of treatment. The radioactivity level in the tissues were determined 72 hours after d9-treatment and shown to be 5 % of the dose in adult rats and 8 % in the old rats. At very high doses, e.g. 200 mg/kg bw given orally, urinary excretion is delayed and faecal excretion is markedly suppressed. There is evidence to suggest involvement of the enterohepatic cycle, but there are no signs of accumulation of 1-chloro-2-nitrobenzene or one of its metabolites (BG-Chemie 2000, Nomeir et al. 1992). After oral administration of 100 mg 1-chloro-2-nitrobenzene/kg bw to rabbits 42 % of the dose was excreted in the urine as glucuronides, 24 % as sulfates, 7 % as mercapturic acids and 9 % as free 2- chloroaniline. Only 2-Chloroaniline (0.3%) could be detected in the faeces. 48 hours after administration elimination was complete (Bray et al. 1956). In tissue, only a very small fraction of the administered radioactivity is recovered (BG-Chemie 2000). The main metabolic routes for 1-chloro-2-nitrobenzene in the body consist in reduction of the nitro group to an amino group and hydroxylation of the benzene ring. Apart from 2-Chloroaniline, the corresponding nitrophenols and aminophenols are formed, which are excreted as conjugates of glucuronic acid and sulfuric acid. 2-Chloroaniline also appears in the urine and faeces in the unconjugated form (BG-Chemie 2000, Bray et al. 1956, Sabbioni 1994, Rickert and Held 1990). During reduction of the nitro group to the amino group, the hydroxylamine compound is formed as a highly reactive intermediate which has been detected both in vivo in rats, and in vitro (BGChemie 2000, Sabbioni 1994).

References:

BG-Chemie, Toxicological Evaluation: Report No. 73, o-Chlornitrobenzol, 11/2000.

Bray H.G., et al., The metabolism of the monochloronitrobenzenes in the rabbit. Biochem. J. 64, 38-44 (1956).

Nomeir A.A. et al., Effect of dose of the percutaneous absorption of 2- and 4-chloronitrobenzene in rats. Drug Metab. Dispos. 20, 436-439 (1992).

Rickert D.E., S.D. Held, Metabolism of chloronitrobenzenes by isolated hepatocytes. Drug Metab. Dispos. 18, 5-9 (1990).

Sabbioni G., Hemoglobin binding of nitroarenes and quantitative structur-activity relationships. Chem. Res. Toxicol. 7, 267-274 (1994).