Two-Week Oral Toxicity Study of 1,4-Dichloro-2-Nitrobenzene in Rats and Mice

Abstract

Subacute toxicity of 1,4-dichloro-2-nitrobenzene (DCNB) was examined by feeding F344 rats and BDF 1 mice of both sexes a diet containing DCNB at 625, 1,250, 2,500, 5,000 or 10,000 ppm (w/w) for 2 weeks. All DCNB-fed rats survived to the end of the 2-week administration period, but 2 male and 6 female mice fed 10,000 ppm died during this period. The subacute toxicity was characterized by lesions affecting the liver, kidney, testis and hematopoietic system. The liver was the most responsive to DCNB, as evidenced by a dose-related increase in relative liver weight in rats and mice and centrilobular hypertrophy of hepatocytes in mice. An alteration in liver-associated lipid metabolism was suggested from the concomitant increases in serum concentrations of total cholesterol and phospholipid. A lower confidence limit of the benchmark dose yielding the response with 10% extra risk (BMDL 10 ) for the relative liver weight indicated that rats were more responsive to DCNB than mice. The kidney lesion was characterized by α α α α α 2υ υ υ υ υ -globulin-accumulated hyaline droplets in the renal tubular epithelial cells only in male rats, as indicated by positive anti-α α α α α 2υ υ υ υ υ -globulin immunohistochemical staining. Testicular and hematopoietic lesions appeared at higher dose levels than did the liver and kidney lesions.

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

“…In this study, it was found that the 13-wk oral administration of DCNB in feed retarded growth rate and induced subchronic toxicity affecting the liver, kidney, testes and blood, and that those toxic signs were essentially similar in nature to those induced by the 2-wk administration of Industrial Health 2005, 43, 597-610 DCNB 9) . The livers of rats and mice and the kidneys of rats were more responsive to DCNB than any other organ affected.…”

“…Body weight, food consumption, organ weight, and hematologic and blood biochemical parameters were analyzed by the same statistical tests as described previously 9) . Histopathologic findings were analyzed by Chi square test.…”

“…The lower confidence limit of the benchmark dose yielding a response with a 10% extra risk (BMDL 10 ) was calculated by the same method as described previously 9) , using BMDS Version 1.3.2 software downloaded from US EPA's NCEA Web site 18) . Daily DCNB intake per body weight was used as a dose parameter, instead of the dietary concentrations of DCNB.…”

“…This compound has been designated as a High Production Volume (HPV) chemical and a Screening Information Data Set (SIDS) chemical for the initial assessment of toxicity and exposure by the Organisation for Economic Co-operation and Development (OECD), in order to protect human health and the environment from the hazardous chemical 1) . There have been few reported data from human poisoning cases [4][5][6] and animal toxicity 2,[7][8][9] available for health risk assessments for workers exposed to DCNB. Our previous paper 9) demonstrated that oral administration of DCNB in feed to rats and mice for 2 wk induced subacute toxicity affecting the liver, kidney, testes and blood, and that the liver was the most responsive to DCNB, as evidenced by increased liver weight and centrilobular hypertrophy of hepatocytes.…”

“…There have been few reported data from human poisoning cases [4][5][6] and animal toxicity 2,[7][8][9] available for health risk assessments for workers exposed to DCNB. Our previous paper 9) demonstrated that oral administration of DCNB in feed to rats and mice for 2 wk induced subacute toxicity affecting the liver, kidney, testes and blood, and that the liver was the most responsive to DCNB, as evidenced by increased liver weight and centrilobular hypertrophy of hepatocytes. DCNB has been evaluated as one of the existing chemical substances with positive mutagenicity, according to the Technical Guideline of the Japanese Industrial Safety and Health Law, which requires that occupational health countermeasures be taken to protect workers from exposure to those mutagenic compounds 10) .…”