The Antiandrogenic Effects of Di(n-butyl) Phthalate in Immature Male Rats: Establishment of Hershberger Assay for Endocrine Disruptors

미성숙 수컷 랫드에서 Hershberger 시험에 의한 Di(n-butyl) Phthalate의 항안드로젠 효과

  • 정문구 (한국화학연구소 안정성연구센터 생식독성실) ;
  • 김종춘 (한국화학연구소 안정성연구센터 생식독성실) ;
  • 서정은 (한국화학연구소 안정성연구센터 생식독성실)
  • Published : 2000.03.01

Abstract

Hershberger assay is known as one of the in vivo-short-term scrrning assays for endocrine disrupting chemicals (EDCs), but this method is not a validated test system. In the present study, the establishment of Hershberger assay to detect EDCs was tried using a model substance, di(n-butyl)phthalate (DBP), a plasticizer for plastics. Thirty-six immature male rats were randomly assigned to six groups: DBP 0, 40, 200, and 1000mg/kg, a positive control (flutamide 20 mg/kg), and a combination group(DBP 1000mg/kg and testosterone 50 ug/kg). DBP and flutamide were administered by gavage to male rats from day 21 to 40 post partum. Testosterone was subcutaneously injected during the same period. We evaluated body weigth gain, weights of ventral prostate, seminal vesicle, and levator ani and bulvocavernous muscle, and serum concentrations of testosterone and lutenizing hormone in male rats. The weights of seminal vesicle and levator ani and bulvocavernous muscle of males receiving 1000mg/kg of DBP was significantly lower than controls. There was no effect of DBP-treatment on body weight gain, prostate weight, and hormone concentrations. In the positive control group, the weights of seminal vesicle and levator ani and bulvocavernous muscle of males receiving 20mg/kg of flutamide were significantly lower than controls. In the combination group, there was no effect of co-treatment of DBP and testosterone on all parameters effect against DBP. This method was found to be a useful short-term screening assay system for EDCs.

Keywords

References

  1. Crit. Rev. Toxicol. v.25 Organochlorine compounds in relation to breast cancer, endometrial cancer, and endometritis; an assessment of the biological and epidemiological evidence Ahlborg, U.G.;Lipworth, L.;Titus-Ernstoff, L.;Hsieh, C.C.;Hanberg, A.;Baron, J.;Tricopoulos, D.;Adami, O.
  2. Health Perspect. v.101 Developmental effects of endocrine-disrupting chemicals in wildlife and humans Colborn, T.;vom Saal, F.S.;Soto, A.M.
  3. A Scientific Detective Story Our Stolen Future. Are we threatening our fertility, intelligence and survival? CoIborn, T.;Dumaoski, D.;Myers, J.P.
  4. Toxicol. Appl. Pharmacol. v.41 Studies on dibutyl phthalate-induced testicular atrophy in the rat: effect on zinc metabolism Cater, B.R.;Cook, M.W.;Gangolli, S.D.;Grasso, P.
  5. Toxicol. Appl. Pharmacol. v.95 Testicular toxicity and reduced Sertoli cell numbers in neonatal rats by d₁(2-ethylhexyl) phthalate and the recovery of fertility as adults Dostal, L.A.;Chapin, R.E.;Stefanski, S.A.;Harris, M.W.;Schwetz, B.A.
  6. Toxicol. Lett. v.69 Teratogenic evaluation of di-n-butyl phthalate in rats Ema, M.;Amano, H.;Itami, T.;Kawasaki, H.
  7. Risk Assessment Forum. U.S. EPA Special report on environmental endocrine disruption: An effects assessment and analysis EPA
  8. Toxicol. Appl. Pharmacol. v.54 Study of the testicular effects and changes in zinc excretion produced by some n-alkyl phthalates in the rat Foster, P.M.D.;Thomas, L.V;Cook, M.W.;Gangolli, S.D.
  9. Toxicol. Appl. Pharmacol. v.63 Changes in ultrastructure and cytochemical localization of zinc in rat testis following the administration of di-n-pentyl phthalate Foster, P.M.D.;Foster, J.R.;Cook, M.W.;Thomas, L.V.;Gangolli, S.D.
  10. Fd. Chem. Toxicol. v.22 Effect of some phthalate esters and other testicular toxins on primary cultures of testicular cells Gray, T.J.B.;Beamand, J.A.
  11. Toxicol. Sci. v.42 Dibutyl phthalate (DBP) induces antiandrogenic but not estrogenic in vivo effects in LE hooded rats Gray, L.E.;Ostby, J.S.;Mylchreest, E.;Foster, P.M.D.;Kelce, W.R.
  12. Environ. Health Perspect v.105 The estrogenic activity of phthalate esters in vitro Harris, C.A.;Henttu, P.;Parker, M.G.;Sumpter, J.P.
  13. Proc. Soc. Exp. Biol. Med v.83 Mytrophic activity of 19-nortestosterone and other steroids determined by modified levator ani muscle method Hershberger, L.;Shipley, E.;Meyer, R.
  14. Endocrinol. v.131 Comparison of the efects of the 5α-reductase inhibitor finasteride and the antiandrogen flutamide on prostate and genital differentiation: Dose-response studies Imperato-McGinley, J.;Sanchez, R.S.;Spencer, J.R.;Yee, B.;Vaughan, E.D.
  15. Environ. Health Perspect v.103 A variety of environmentally persistent chemicals, including some phthalate plasticizers, are weakly estrogenic Jobling, S.;Reynolds, T.;White, R.;Parker, M.G.;Sumpter, J.R.
  16. J. Anat. v.190 The effects of pre-and postnatal exposure to the nonsteroidal anti-androgen flutamide on testis descent and morphology in the Albino Swiss rat Kassim, N.M.;McDonald, S.W.;Reid, O.;Bennet, N.K.;Gilmore, D.P.;Payne, A.P.
  17. Fund. Appl. Toxicol. v.36 In vitro and in vivo assessments of the alleged estrogen receptor-mediated activities of phthalate esters Meek, M.D.;Clemons, J.;Wu, Z.F.;Fielden, M.R.;Zacharewski, T.
  18. Toxicol. Appl. Pharmacol. v.156 Disruption of androgen-regul- ated male reproductive development by di(n-butyl) phthalate during late gestation in rats is different from flutamide Mylchreest, E.;Sar, M.;Cattley, R.C.;Foster, P.M.D.
  19. Toxicol. Appl. Pharmacol. v.156 no.81-95 Distruption of androgen-regul- ated male reproductive development by di(n-butyl) phthalate during late gestation in rats is differenct form flutamide Mylchreest. E.;Sar. M.;Cattley. R.C.;Foster. P.M.D.
  20. Toxicol. Sci. v.43 Male reproductive tract malformations in rats following gestational and lactational exposure to di(n-butyl) phthalate: An antiandrogenic mechanism? Mylchreest, E.;Cattley, R.C.;Foster, P.M.D.
  21. SAS/STAT User's Guide (Version 6) (Fourth Edition) SAS Institute Inc.
  22. J. Reprod. Fertil. v.96 Disturbed testicular descent in the rat after prenatal exposure to the antiandrogen flutamide van der Schoot, P.
  23. Toxicol. Sci. v.42 Phthalate monoesters: Interactions with human sex hormone binding globulin and human estrogen receptors Wu, Z.F.;Hodgert, J.H.;Hammond, G.;Zacharewski, T.