Thirteen-Week Oral Toxicity Study of l,4-Dichloro-2-Nitrobenzene in Rats and Mice

Abstract

Subchronic toxicity of 1,4-dichloro-2-nitrobenzene (DCNB) was examined by feeding F344 rats and BDF 1 mice of both sexes a diet containing 1,481, 2,222, 3,333, 5,000 or 7,500 ppm DCNB (w/w) for 13 wk. Oral administration of DCNB in feed to rats and mice retarded growth rates and induced subchronic toxicity affecting the liver, kidney, testes and blood. Liver and kidney were most responsive to DCNB. BMDL 10 values for relative liver weight were 12.0 and 22.6 mg/kg/d for male and female rats, respectively, and 88.7 and 94.4 mg/kg/d for male and female mice, respectively. Increased liver weights and centrilobular hypertrophy of hepatocytes were observed in the DCNB-fed rats and mice of both sexes. Both increased serum activities of AST and ALT and liver necrosis occurred in the DCNB-fed mice. Increased incidences of hyaline droplets and granular casts in the proximal renal tubules were observed only in the DCNB-fed male rats, indicating α α α α α 2υ υ υ υ υ -globulin nephropathy. Eosinophilic droplets in the renal tubular cells and increased BUN concentrations occurred in the DCNB-fed female rats. DCNB-induced testicular and hematologic changes were noted in rats and mice. On the basis of these results, the highest dose level for the 2-yr bioassay study of rodent carcinogenicity was determined to be 2,000 ppm.

Enhancing developmental and reproductive toxicity knowledge: A new AOP stemming from glutathione depletion

“…A long term (13-week) oral toxicity study with 2,5-DCNB was also conducted in rats and mice and similar toxicities were observed ( Yamazaki et al, 2005a ). In this study, the maximum dose of 2,5-DCNB was 7500 ppm and germ cell necrosis was observed in rat testes from 2222 ppm.…”

Nephrotoxic Potential of Putative 3,5-Dichloroaniline (3,5-DCA) Metabolites and Biotransformation of 3,5-DCA in Isolated Kidney Cells from Fischer 344 Rats

“…Chlorinated nitrobenzenes are nephrotoxicants in vivo and in vitro [34,52,53]. Rickert and Held [3] found that hepatic microsomes from male Fischer 344 rats metabolized 3chloronitrobenzene by reduction of the nitro group to form 3-chloroaniline, indicating that metabolism between 3,5-DCA and 3,5-DCNB is reversible.…”