Toxicological Research

Korean Society of Toxicology & Korea Environmental Mutagen Society (한국독성학회)
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Anti-Androgenic Activity of Phthalate Esters (Di(2-ethylhexyl) Phthalate, Di(n-butyl) Phthalate, and Butylbenzyl Phthalate) in the Rodent 10-day Hershberger Assay using Immature Castrated Male Rats

  • Kang, Il-Hyun (Department of Toxicology, National Institute of Toxicological Research, Korea Food and Drug Administration) ;
  • Kim, Hyung-Sik (College of Pharmacy, Pusan National University) ;
  • Kim, Tae-Sung (Department of Toxicology, National Institute of Toxicological Research, Korea Food and Drug Administration) ;
  • Moon, Hyun-Ju (Department of Toxicology, National Institute of Toxicological Research, Korea Food and Drug Administration) ;
  • Kim, In-Young (Department of Toxicology, National Institute of Toxicological Research, Korea Food and Drug Administration) ;
  • Kang, Tae-Seok (Department of Toxicology, National Institute of Toxicological Research, Korea Food and Drug Administration) ;
  • Park, Kui-Lea (Department of Toxicology, National Institute of Toxicological Research, Korea Food and Drug Administration) ;
  • Choi, Kwang-Sik (Department of Toxicology, National Institute of Toxicological Research, Korea Food and Drug Administration) ;
  • Han, Soon-Young (Department of Toxicology, National Institute of Toxicological Research, Korea Food and Drug Administration)
  • Published : 2005.09.01
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Abstract

The rodent Hershberger assay is considered as a potential short term in vivo screening method for the detection of androgenic or anti-androgenic compounds. The objective of this study was to evaluate the anti-androgenic activities of di(2-ethylhexyl) phthalate (DEHP), di(n-butyl) phthalate (DBP), and butylbenzyl phthalate (BBP). A 10-day Hershberger assay was performed using immature Sprague-Dawley male rats castrated at 6 weeks of age. Tastosterone propionate (TP, 0.4 mg/kg/day) was administered s.c. to castrated male rats and followed by flutamide (1, 5, 10, or 20 mg/kg/day) treatment for 10 days by oral gavage. Similarly, DEHP, DBP, or BBP were also administered by oral gavage at 250, 500, or 1000 mg/kg/day after TP (0.4 mg/kg/day) administration. As expected, flutamide significantly inhibited the TP-induced re-growth of seminal vesicles, ventral prostate, and Levator ani plus bulbocavernosus muscles (LABC) at 1 mg/kg/day and above, and Cowper's glands and glans penis at 5 mg/kg/day and above. DEHP significantly (p<0.05) decreased the seminal vesicles, ventral prostate, LABC and Cowper's glands weights at 1000 mg/kg/day. BBP at 1000 mg/kg/day significantly inhibited TP-induced re-growth of the LABC in the immature castrated male rats, whereas ventral prostate, seminal vesicles, and Cowper's glands weights were unaffected. In contrast to DEHP, DBP did not affect accessory sex organ weights at any concentration. Body weights, combined adrenal glands, and kidney weights were not affected, but liver weights were significantly increased at high dosages in the DEHP, DBP, and BBP treatment groups. Our observations strongly suggest that DEHP acts as an androgen antagonist at the high dose (i.e., 1000 mg/kg/day).

Keywords

References

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