The Estrogenic Effects of Methoxychlor in Pubertal Female Rats: Establishment of Thyroid Assay for Endocrine Disruptors

사춘기 암컷 랫드에서 갑상선 시험에 의한 Methoxychlor의 에스트로젠 효과

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

Abstract

Recently, there is a worldwide concern that a great number of man-made chemicals have a hormone-like action both in humans and in animals. EPA and OECD are developing screening programs using validated test systems to determine whether certain substances may have an effect on humans. In the present study, the establishment of in vivo short-term test system for pubertal female assay with thyroid to detect endocrine disrupting chemicals was tried using a model substance, methoxychlor (MC), a chlorinated hydrocarbon insencticide. Forty female rats were assigned to four groups. MC was administered at dose levels of 0, 8, 40 and 200mg/kg by gavage to female rats from day 21 post partum to the completion of vaginal opening. We evaluated body weight change, age at vaginal opening, onset of estrous cyclicity, age at first esturs, ovary weight, and serum concentrations of thyroxine and thyroid stimulating hormone in female rats. The age at vaginal opening of females receiving 40 200mg/kg was significantly younger than control. The onset of estrus cyclicity and age at first estrus of females receiving 200mg/kg was also younger than controls. There was no effect of treatment on body weight, ovary weight, and hormone concentration. Based on these results, it can be concluded that application of MC at dose level of 40mg/kg affects the vaginal opening and application of MC at dose level of 200mg/kg accelerates the vaginal opening and the onset of estrus cylicity.

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. Biochem. Pharmacol. v.27 Studies on the in vivo and in vitro estrogenic activities of methoxychlor and its metabolites Bulger, W.H.;Muccitelli, R.M.;Kupfer, D.
  3. Br. Med. J. v.305 Evidence for decreasing quality of semen during past 50 years Carlsen, E.;Giwercman, A.;Keiding, N.;Stakkebaek, N.
  4. Environ. Health Perspect. v.101 Developmental effects of endocrine-disrupting chemicals in wildlife and humans Colborn, T.;vom Saal, F.S.;Soto, A.M.
  5. A Scientific Detective Story Our Stolen Future. Are we threatening our fertility. intelligence and survival? Colborn, T.;Dumaoski, D.;Myers, J.P.
  6. Risk Assessment Forum Special report on environmental endocrine disruption: An effects assessment and analysis EPA
  7. Biol. Reprod v.42 Morphological and biochemical alterations in reproductive tracts of neonatal female mice treated with the pesticide methoxychlor Eroschenko, V.P.;Cooke, P.S.
  8. Reprod. Toxicol. v.10 Estradiol or methoxychlor stimulates estrogen receptor expression in uteri Eroschenko, V.P.;Rourke, A.W.;Sims, W.F.
  9. Fundam. Appl. Toxicol. v.12 A doseresponse analysis of methoxychlor-induced alterations of reproductive development and function in the rat Gray, L.E.;Ostby, J.S.;Ferrell, J.M.
  10. Environ. Health Perspect. v.104 no.Suppl. 4 Research needs for the risk assessment of health and environmental effects of endocrine disruptors: a report of the U.S. EPA-sponsered workshop Kavlock, R.J.;Daston, G.P.;DeRosa, D.;Fenner-Crisp, P.;Gray, L.E.;Kaattari, S.;Lucier, G.;Luster, M.
  11. SAS/STAT User's Guide (Version 6) (Fourth Edition) SAS Institute Inc.
  12. Reprod. Toxicol. v.8 Response of adult murine uterine epithelium to 50% methoxychlor Schwartz, W.J.;Wink, C.S.;Johnson, W.D.
  13. Environ. Health Perspect. v.103 Gestational and lactational exposure of rats to xenoestrogens results in reduced testicular size and sperm production Sharpe, R.M.;Fisher, J.S.;Millar, M.M.;Jobling, S.;Sumpter, J.P.
  14. Science v.133 Uterotrophic action of the insecticide methoxychlor Tullner, W.W.
  15. Reprod. Toxicol. v.7 Purified methoxychlor stimulates the reproductive tract in immature female mice Walters, L.M.;Rourke, A.W.;Eroschenko, V.P.
  16. Toxicol. Appl. Pharmacol. v.14 Estrogenic action of DDT and its analogs Welch, R.M.;Levin, W.;Conney, A.H.