Risk assessment for estrogenic effect of the suspected endocrine disrupting pesticides

내분비계 장애추정농약에 대한 에스트로겐성 영향검색 및 위해성 평가

  • Lee, Je-Bong (National Institute of Agricultural Science and Technology, RDA) ;
  • Shin, Jin-Sup (National Institute of Agricultural Science and Technology, RDA) ;
  • Lee, Hee-Dong (National Institute of Agricultural Science and Technology, RDA) ;
  • Jeong, Mi-Hye (National Institute of Agricultural Science and Technology, RDA) ;
  • You, Are-Sun (National Institute of Agricultural Science and Technology, RDA) ;
  • Kang, Kyu-Young (Department of Envrion. Biotechnology, Gyeongsang National University)
  • Published : 2004.06.30

Abstract

The present study was conducted to test and evaluate estrogenic effect of 17 pesticides including benomy1 and carbaryl, being suspected as endocrine disrupting chemicals. For estrogenic effect examination, luciferase assay were achieved with human ovarian cancer cell, BG1Luc4E2. Estrogenic effects of cypermethrin, dicofol, endosulfan, esfenvalerate, and fenvalerate were observed at the concentration of $10^{-5}$ M by estrogen receptor binding assay. Relative luciferase potency and relative luciferase effects compared with $10^{-10}$ M 17 $\beta$-estradiol were $10^{-5}$, 56% for dicofol, and $10^{-5}$, 72% for endosulfan, respectively. Estimated maximum daily intake for pesticides was calculated from maximum residue limit of agricultural commodity and food consumption was 1.2298 mg/person. Theoretically calculated blood estrogen level from dietary intake for pesticides based on MRL in Korea, 3.075 ng/L was equivalent to 15% of estrogen concentration in normal blood, but practical monitoring data, 0.01938 ng/L was equal to 0.09693% of estrogen concentration in normal blood.

현재 국내 사용중이며 내분비계 장애추정농약으로 분류된 benomyl, carbaryl, endosulfan등 17종 농약에 대한 estrogen성 영향을 검색하기 위하여 인체난소암세포(BG1Luc4E2)를 이용한 luciferase assay를 수행하였으며, luciferase assay에서 Eeq를 산출한 후 내분비계 장애추정 농약의 에스트로겐성 영향에 대한 식이섭취 위험도 평가를 실시하였다. Estrogen 수용체 결합시험에서 cypermethrin, dicofol, endosulfan, esfenvalerate 및 fenvalerate가 $10^{-5}$ M에서 최고 영향이 관찰되었고, mancozeb 등 8종 농약은 약한 영향이 관찰되었으며, benomyl 등 나머지 4종 농약은 영향이 없었다. 이들 중 활성이 비교적 강한 dicofol 및 endoeulfan의 1 nmol 17 $\beta$-estradiol에 대한 RLP 와 RLU는 dicofol의 경우 $10^{-5}$ 및 56%이었구, endosulfan은 $10^{-5}$ 및 72%이었다. MRL을 이용한 식이섭취 위험도 평가 결과 농약들의 추청 1일 최대농약섭취량은 cypermethrin 0.667, dicofol 0.1462, endosulfan 0.2066 및 lenvalerate/esfenvalerate 0.2098 mg/person으로 총 추정 1일 최대 농약섭취량이 1.2298 mg/person이었고, 남성 혈중 에스트로겐 증가 농도는 3.075 ng/L로 정상농도에 비해 15%정도 증가하였으나, 국내 모니터링 성적을 기준으로 평가한 결과 남성혈중 에스트로겐 증가 농도는 0.01938 ng/L로 정상농도에 비해 0.09693%정도 증가하였다.

Keywords

References

  1. Boenke, A., C. Searle, T. Karjalainen(2002) Contribution of European research to endocrine disruptors. analytica Chimica Acta 473:161-165 https://doi.org/10.1016/S0003-2670(02)00773-0
  2. Denison, M. S., A. Pandini, S. R.Nagy(2002) Ligand binding and activation of the Ah receptor. Chemico-Biological Interaction 141:3-24 https://doi.org/10.1016/S0009-2797(02)00063-7
  3. Denison, M. S., D. Phelan, G. M. Winter, M. H. Ziccardi(1998) Carbaryl, a Carbamate insecticides, is a Ligend for the Hepatic Ah(Dioxin) Receptor. Toxicology and Applied Pharmacology 152:406-414 https://doi.org/10.1006/taap.1998.9999
  4. Giesy, J. P., K. Hilscherova, P. D. Jones, K. Kannan, M. Machala(2002) Cell bioassay for detection of aryl hydrocarbon(AhR) and estrogen receptor(ER) mediated activity in environmental samples. Marine Pollution Bulletin 45:3-16 https://doi.org/10.1016/S0025-326X(02)00097-8
  5. Gi1lesby, B. E. and T. R. Zacharewiski(1998) Exoestrogens : mechanism of action and strategies for identification and assessment. Environ. Toxicol. Chem. 17:3-14
  6. Go, V., M. S. Wolff, B. G. T. Pogo(1999) Estrogenic potential of certain pyrethroid compounds in the MCF-7 human breast carcinoma cell line. Environ. Health perspect. 107:173-177
  7. Klotz, D. M., B. S. Beckman, S. M. Hill, J. A. Mclachlan, M. R.Walters, S.F.Amold (1996) Identification of environmental chemicals with estrogenic activity using a combination of in virto assays. Environ. Health Perspect. 104(10) : 1084-1089
  8. Legler, J., C. Brink, A. Brower, D. Vethaak, P. VanDerSaag, T. Murk, B. Burg(1998) Assessment of (anti)estrogenic compounds using a stably transfected luciferase reporter gene assay in the human T47-D breast cancer cell line. Organohalogen Com. 35 : 265-268
  9. Machala, M., and J. Vondracek(1998) Estrogenic activity of xenobiotics. Vet. Med. 10:311-317
  10. Oh, S. M., S. Y. Cheong, Y. Y. Sheen, K. H. chung (2000) Quantitative assessment of estrogenic activity in the water environment of Korea by the E-Screen assay. The Science of the Total Environment 263:161-169 https://doi.org/10.1016/S0048-9697(00)00697-5
  11. Petit, F., P. Le-Goff, J. P. Cravedi, Y. Valotaire, F. Pakdel (1997) Two complementary bioassays for screening the estrogenic potency of xenobiotics : recombinant yeast for trout estrogen receptor and trout hepatocytes cultures. J. Mol. endocrinology. 19:321-335
  12. Rogers, J. M., and M. S. Denison (2000) Recombinant cell bioassays for endocrine disruptors : Development of a stably transfected human ovarian cell line for the detection of estrogenic and anti-estrogenic chemicals. In vitro and molecular toxicology 13(1):67 -82
  13. Rogers, J. M., and M. S. Denison (2002) Analysis of the anti-estrogenic activity of 2,3,7,8-Tetrachlorodibenzop-dioxin in human ovarian carcinoma BG-l cells. Molecular pharmacology 61(6):1393-1403 https://doi.org/10.1124/mol.61.6.1393
  14. Seidel, S. D., V.L.G.M. Winter, W.J.Rogers, E.I.Eugenio, and .S.Denison (2000) Ah Receptor-based chemical screening bioassay : application and limitations for the detection of Ah receptor agonist. Toxicological Sci- ence 55:107-115 https://doi.org/10.1093/toxsci/55.1.107
  15. Shaw, I. and S. McCully (2002) A review of the potential impact of dietary endocrine disrupters on the consumer. International Journal of Food science and technology 37:471-476
  16. Soto, A. and S. Carlos (1985) The role of estrogens on the proliferation of human breast tumor cells(MCF-7). Journal of steroid biochemistry 23(1):87-94 https://doi.org/10.1016/0022-4731(85)90265-1
  17. US/EPA (1997) EPA special report on. endocrine disruption
  18. US/EPA (1998) Final report of endocrine disruptor sereening and testing advisory committee
  19. US/EPA (2002) Federal register notice
  20. iccardi, M. H., I. A. Gardner, J. A. K. Mazet, M. S. Denison (2002) Application of the luciferase cell culture bioassay for the detection of refined petroleum products. Marine pollution Bulletin 44:893-991
  21. 국립환경연구원(1999) 내분비계 장애물질 이해와 대응
  22. 농업과학기술원(2003) 농약잔류허용기준(내부자료)
  23. 농업과학기술원(2002) 농약 모니터링 성적(내부자료)
  24. 보건복지부(1998) 국민영양조사결과보고서