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26-Week carcinogenicity study of di-isodecyl phthalate by dietary administration to CB6F1-rasH2 transgenic mice

  • Genotoxicity and Carcinogenicity
  • Published:
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Abstract

This study examined the carcinogenic potential of di-isodecyl phthalate (DIDP) in rasH2 mice. DIDP was administered to 15 rasH2 mice/gender/group at dietary levels of 0, 0.1, 0.33, or 1% and 15 wild-type mice/gender/group at dietary levels of 0 and 1% for 26 weeks. Non-neoplastic changes were observed in the liver (parenchymal inflammation, fatty changes, diffuse hepatocyte hypertrophy with eosinophilic granules and focal necrosis) and kidneys (tubular basophilia and tubular hyperplasia) after administration of DIDP in the rasH2 and wild-type mice. In the neoplastic lesions, there were a higher number of hepatocellular adenomas in the male rasH2 mice receiving 1% DIDP, compared with the findings in the liver of control rasH2 mice or wild-type mice. The incidence of hepatocellular adenomas in the 0.1, 0.33, and 1% DIDP exposed rasH2 mice was 7% (1/15), 7% (1/15), and 33% (5/15), respectively. This study adds a set of results for an additional test chemical for the performance of the rasH2 short-term transgenic model to the existing database of 3 compounds (WY-14643, DEHP, and clofibrate) tested in the ILSI/HESI ACT project.

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Abbreviations

DIDP:

Di-isodecyl phthalate

MNU:

N-Methyl-N-nitrosourea

DEHP:

Di(2-ethylhexyl)phthalate

DINP:

Di-isononyl phthalate

CIEA:

Central Institute for Experimental Animals

ILSI-HESI:

International Life Sciences Institute/Health and Environmental Science Institute

Tg:

Transgenic

WT:

Wild-type

ICH:

International Conference on Harmonization

MTD:

Maximum Tolerated Dose

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Acknowledgments

The authors wish to thank Professor Byeongwoo Ahn (Veterinary Pathologist, Chungbuk National University) for performing the pathology peer review. This study was supported by a grant from the Korea National Toxicology Program from the National Institute of Toxicological Research of Korea Food and Drug Administration.

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Authors and Affiliations

  1. ELEGI/Colt Laboratory, Centre for Inflammation Research, The Queen’s Medical Research Institute, The University of Edinburgh, 47 Little France Crescent, Edinburgh, EH16 4TJ, UK

    Wan-Seob Cho

  2. Nutrition and Functional Food Research Team, National Institute of Food and Drug Safety Evaluation, 231 Jinhoungno Eunpyung-ku, Seoul, 122-704, Korea

    Jayoung Jeong

  3. Division of Toxicological Research, National Institute of Food and Drug Safety Evaluation, 231 Jinhoungno Eunpyung-ku, Seoul, 122-704, Korea

    Mina Choi & Sue Nie Park

  4. Good Laboratory Practice Center, Hoseo University, Sechul-ri 165, Baebang-eup, Asan city, Choongchungnam-do, South Korea

    Beom Seok Han

  5. Department of Pathology, Huntingdon Life Sciences, Woolley Road, Alconbury, Huntingdon, Cambridgeshire, PE28 4HS, UK

    Woo-Chan Son

Authors
  1. Wan-Seob Cho
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  2. Jayoung Jeong
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  3. Mina Choi
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  4. Sue Nie Park
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  5. Beom Seok Han
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Corresponding authors

Correspondence to Beom Seok Han or Woo-Chan Son.

Additional information

W.-S. Cho and J. Jeong contributed equally.

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Cho, WS., Jeong, J., Choi, M. et al. 26-Week carcinogenicity study of di-isodecyl phthalate by dietary administration to CB6F1-rasH2 transgenic mice. Arch Toxicol 85, 59–66 (2011). https://doi.org/10.1007/s00204-010-0536-6

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  • DOI: https://doi.org/10.1007/s00204-010-0536-6

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