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Species differences in the metabolism of di(2-ethylhexyl) phthalate (DEHP) in several organs of mice, rats, and marmosets

  • Toxicology and Metabolism
  • Published:
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Abstract

To clarify species differences in the metabolism of di(2-ethylhexyl) phthalate (DEHP) we measured the activity of four DEHP-metabolizing enzymes (lipase, UDP-glucuronyltransferase (UGT), alcohol dehydrogenase (ADH), and aldehyde dehydrogenase (ALDH)) in several organs (the liver, lungs, kidneys, and small intestine) of mice (CD-1), rats (Sprague–Dawley), and marmosets (Callithrix jacchus). Lipase activity, measured by the rate of formation of mono(2-ethylhexyl) phthalate (MEHP) from DEHP, differed by 27- to 357-fold among species; the activity was highest in the small intestines of mice and lowest in the lungs of marmosets. This might be because of the significant differences between Vmax/Km values of lipase for DEHP among the species. UGT activity for MEHP in the liver microsomes was highest in mice, followed by rats and marmosets. These differences, however, were only marginal compared with those for lipase activity. ADH and ALDH activity also differed among species; the activity of the former in the livers of marmosets was 1.6–3.9 times greater than in those of rats or mice; the activity of the latter was higher in rats and marmosets (2–14 times) than in mice. These results were quite different from those for lipase or UGT activity. Because MEHP is considered to be the more potent ligand to peroxisome proliferator-activated receptor α involved in different toxic processes, a possibly major difference in MEHP-formation capacity could be also considered on extrapolation from rodents to humans.

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Abbreviations

ADH:

Alcohol dehydrogenase

ALDH:

Aldehyde dehydrogenase

DEHP:

Di(2-ethylhexyl) phthalate

2-EH:

2-Ethylhexyanol

2-EHA:

2-Ethylhexanoic acid

MEHP:

Mono(2-ethylhexyl) phthalate

2-POET:

2-Phenoxyethanol

PPARα:

Peroxisome proliferator-activated receptor alpha

UGT:

UDP-glucuronyl transferase

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Acknowledgements

This study was supported by a research grant from the Japan Ministry of Environment (2001) and a Grant-in-Aid for JSPS fellows from the Japan Ministry of Education, Culture, Sports, Science and Technology (14,2531).

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Authors and Affiliations

  1. Department of Occupational and Environmental Health, Nagoya University Graduate School of Medicine, 65 Tsurumai-cho, Showa-ku, 466-8550, Nagoya, Japan

    Yuki Ito, Osamu Yamanoshita, Gaku Ichihara, Hailan Wang & Tamie Nakajima

  2. Department of Biochemistry, Rakuno Gakuen University School of Veterinary Medicine, 069-8501, Ebetsu, Japan

    Hiroshi Yokota

  3. National Institute of Industrial Health, 214-8585, Kawasaki, Japan

    Ruisheng Wang

  4. Department of Safety Science Research, Mitsubishi Research Institute Company Limited, 314-0255, Kashima, Japan

    Yoshimasa Kurata

  5. Department of Medical Technology, Nagoya University School of Health Sciences, 461-8673, Nagoya, Japan

    Kenji Takagi

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  1. Yuki Ito
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  2. Hiroshi Yokota
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  3. Ruisheng Wang
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  9. Tamie Nakajima
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Correspondence to Tamie Nakajima.

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Ito, Y., Yokota, H., Wang, R. et al. Species differences in the metabolism of di(2-ethylhexyl) phthalate (DEHP) in several organs of mice, rats, and marmosets. Arch Toxicol 79, 147–154 (2005). https://doi.org/10.1007/s00204-004-0615-7

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  • DOI: https://doi.org/10.1007/s00204-004-0615-7

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