Abstract
Carcinogenicity and chronic toxicity of 2,4-dichloro-1-nitrobenzene (2,4-DCNB) were examined by dietary administration to F344/DuCrj rats and Crj:BDF1 mice of both sexes for 2 years. Dietary administration commenced when the animals were 6 weeks old. The dietary concentration of 2,4-DCNB was 0 (control), 750, 1,500 and 3,000 ppm (w/w) for male and female rats; 0, 750, 1,500 and 3,000 ppm for male mice; and 0, 1,500, 3,000 and 6,000 ppm for female mice. In rats, there was a dose-dependent and significant induction of renal cell adenomas and carcinomas in both sexes and of preputial glands adenomas in males. In all the 2,4-DCNB-fed groups of both sexes, the incidence of atypical tubular hyperplasia, a pre-neoplastic lesion in the kidney, in the proximal tubule was significantly increased. In mice, there was a dose-dependent and significant induction of hepatocellular adenomas, hepatocellular carcinomas, hepatoblastomas and peritoneal hemangiosarcomas in both sexes. The incidence of acidophilic hepatocellular foci was also significantly increased in female mice. Thus, clear evidence of carcinogenic activity of 2,4-DCNB by 2-year feeding was demonstrated in both rats and mice.
Similar content being viewed by others
References
Anden CC, Kanerva RK, Ridder G, Stone LS (1984) The pathogenesis of nephrotoxicity of volatile hydrocarbons in the male rats. In: Mehlman MA, Hemstree CP III, Thorpe JJ, Weaver NK (eds) Renal effects of petroleum hydrocarbons. Princeton Scientific Publishers Inc., Princeton, pp 107–120
Bannasch P, Griesemer RA, Anders F, Becker R, Cabral J R, Della Porta G, Feron VJ, Henschler D, Ito N, Kroes R, Magee P N, McKnight B, Mohr U, Montesano R, Napalkov NP, Pegg AE, Rao GN, Turusov VS, Wilbourn J (1986) Selection of doses. In: Montesano R, Bartsch H, Vainio J, Wilbourn J, Yamasaki H (eds) Long-term and short-term assays for carcinogens: a critical appraisal. IARC scientific publications No. 83, Lyon, pp 34–36
Beratergreimium für Umweltrelevant Altstoffe (BUA) (1991) 3-Dichloro-4-nitrobenzene. In: Syuttgart S (ed) GDCh-Advisory committee on existing chemicals of environmental relevance. Report 64, Hirzel Wissenschaftliche Verlagsgesellschaft, Germany
Charbonneau M, Strasser J Jr, Lock EA, Turner MJ Jr, Swenberg JA (1989) Involvement of reversible binding to α2u -globulin in 1,4-dichlorobenzene-induced nepthropathy. Toxicol Appl Pharmacol 99:122–132
Dekant W, Metzler M, Henschler D (1986) Identification of S-1,2-dichlorovinyl-N-acetyl-cysteine as a urinary metabolite of trichloroethylene: a possible explanation for its nephrocarcinogenicity in male rats. Biochem Pharmacol 35:2455–2458
Dekant W, Berthold K, Vamvakas S, Henschler D, Anders MW (1988) Thioacylating intermediates as metabolites of S-(1,2-dichlorovinyl)-L-cysteine and S-(1,2,2-trichlorovinyl)-L-cysteine formed by cysteine conjugate β-lyase. Chem Res Toxicol 1:175–178
Elfarra AA, Jakobson I, Anders MW (1986) Mechanism of S-(1,2-dichlorovinyl) glutathione-induced nephrotoxicity. Biochem Pharmacol 35:283–288
Frith CH, Ward JM, Turusov VS (1994) Tumours of the liver. In: Turusov VS, Mohr U (eds) Pathology of tumours in laboratory animals. Vol. II Tumours of the mouse. IARC Scientific Publication No. 111, Lyon, pp 223–248
Hard GC, Alden CL, Stula EF, Trump BF (1995) Proliferrative lesions of the kidney in rats. In: Guides for toxicologic pathology. STP/ARP/AFIP, Washington, DC, pp 1–19
Japan Chemical Industry Ecology-Toxicology and Information Center (JETOC) (1996) 2,4-Dichloro-1-nitrobenzene. In: Mutagenicity test data of existing chemical substances. Based on toxicity investigation system of the Industrial Safety and Health Law. JETOC, Tokyo, p 60 (323–324, 551–552, in Japanese)
Japan Industrial Safety and Health Association (2004) A list of mutagenic chemicals. In: General guidebook on industrial health 2004. Japan Industrial Safety and Health Association, Tokyo, pp 127–132
Kawai K (1980) Report from working group on long-term holding of experimental animals. Exp Anim 29:181–231 (in Japanese)
MacFarland HM, Ulrich CE, Holdsworth CE, Kitchen DN, Halliwell WH, Blum SC (1984) A chronic inhalation study with unleaded gasoline vapor. J Am Coll Toxicol 3:231–248
Montgomery CA, Seely JC (1990) Kidney. In: Boorman GA, Eustis SL, Elwell MR, Montgomery CA Jr, MacKenzie WF (eds) Pathology of the fischer rat. Academic Press Inc., San Diego, pp 127–153
National Research Council (NRC) (1996) Guide for the care and use of laboratory animals. Institute of Laboratory Animal Resources Commission on Life Sciences. NRC. National Academy Press, Washington, DC
National Toxicology Program (NTP) (1990) NTP technical report on the toxicology and carcinogenesis studies of d-limonene (CAS No. 5989-27-5) in F344/N rats and B6C3F1 mice (gavage studies). NTP TR 347. NIH Publication No. 90-2802
Ohnishi M, Yamazaki K, Yamamoto S, Matsushima T (2004) Characterization of N-acetylcysteine conjugate in yellow urine by oral administration of 1,4-dichloro-2-nitrobenzene in rats. J Health Sci 50:319–322
Ohnishi M, Take M, Yamamoto S, Fukushima S, Yajima H (2009) Identification of an N-acetylcysteine conjugate in the urine after oral administration of 2,4-dichloro-1-nitrobenzene to rats. J Toxicol Sci 34:233–237
Organisation for Economic Co-operation and Development (OECD) (1981) OECD guideline for testing of chemicals 451 for “Carcinogenicity studies” Adopted 12 May 1981. OECD, Paris
Organisation for Economic Co-operation and Development (OECD) (1996) 2,4-Dichloronitrobenzene. In: Screening Information Data Set (SIDS): initial assessment report for SIAM4. OECD, Paris
Organisation for Economic Co-operation and Development (OECD) (1998) OECD series on principles of good laboratory practice. Series on principles of good laboratory practice and compliance monitoring No. 1. ENV/MC/CHEM (98), vol 17, OECD, Paris
Organisation for Economic Co-operation and Development (OECD) (2004) The 2004 OECD list of high production volume chemicals. Environment directorate, OECD, Paris. http://www.oecd.org/dataoecd/55/38/33883530.pdf Accessed 23 May 2012
Sontag JM, Page NP, Saffiotti U (1976) Guidelines for carcinogen bioassay in small rodents. NCI-CG-TR-1. DHHS Publication (NIH) 76-801. National Cancer Institute, Bethesda (MD)
United States Environmental Protection Agency (US EPA) (2009) Benchmark dose software version 2.1 user’s manual. 53-BMDS-RPT-0028, US EPA. Washington, DC
Vambakas S, Elfarra AA, Dekant W, Henschler D, Anders MW (1988) Mutagenicity of amino acid and glutathione S-conjugates in the Ames test. Mutat Res 206:83–90
Yamazaki K, Aiso S, Matsumoto M, Kano H, Arito H, Nagano K, Yamamoto S, Matsushima T (2006) Carcinogenicity and chronic toxicity of 1,4-dichloro-2-nitorobenzene in rats and mice by two years feeding. Ind Health 44:230–243
Acknowledgments
This work was contracted and supported by the Ministry of Health, Labour and Welfare, Japan. We wish to express our thanks to Dr. David B. Alexander, Nanomaterial Toxicology Project Laboratory, Nagoya City University, for proofreading this manuscript.
Conflict of interest
The authors declare that they have no conflict of interest.
Author information
Authors and Affiliations
Corresponding author
Rights and permissions
About this article
Cite this article
Kano, H., Suzuki, M., Senoh, H. et al. 2,4-Dichloro-1-nitrobenzene exerts carcinogenicities in both rats and mice by two years feeding. Arch Toxicol 86, 1763–1772 (2012). https://doi.org/10.1007/s00204-012-0890-7
Received:
Accepted:
Published:
Issue Date:
DOI: https://doi.org/10.1007/s00204-012-0890-7