Journal of Environmental Health Sciences (한국환경보건학회지)

Korean Society of Environmental Health (한국환경보건학회)
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Immatured Type Uterotrophic Assay for Estrogenicity Evaluation of DEHA

미성숙 랫드 자궁비대반응시험을 이용한 DEHA의 내분비계 장애작용 평가

  • Park, Ki-Dae (Korea Food and Drug Administration, National Institute of Toxicological Research) ;
  • Han, Beom-Seok (Korea Food and Drug Administration, National Institute of Toxicological Research) ;
  • Jeong, Ja-Young (Korea Food and Drug Administration, National Institute of Toxicological Research) ;
  • Oh, Jae-Ho (Korea Food and Drug Administration, National Institute of Toxicological Research) ;
  • Cho, Wan-Seob (Korea Food and Drug Administration, National Institute of Toxicological Research) ;
  • Cho, Min-Jeong (Korea Food and Drug Administration, National Institute of Toxicological Research) ;
  • Choi, Mi-Na (Korea Food and Drug Administration, National Institute of Toxicological Research) ;
  • Kim, Sung-Joon (Korea Food and Drug Administration, National Institute of Toxicological Research) ;
  • Kim, Seung-Hee (Korea Food and Drug Administration, National Institute of Toxicological Research)
  • 박기대 (식품의약품안전청 국립독성과학원) ;
  • 한범석 (식품의약품안전청 국립독성과학원) ;
  • 정자영 (식품의약품안전청 국립독성과학원) ;
  • 오재호 (식품의약품안전청 국립독성과학원) ;
  • 조완섭 (식품의약품안전청 국립독성과학원) ;
  • 조민정 (식품의약품안전청 국립독성과학원) ;
  • 최미나 (식품의약품안전청 국립독성과학원) ;
  • 김성준 (식품의약품안전청 국립독성과학원) ;
  • 김승희 (식품의약품안전청 국립독성과학원)
  • Published : 2007.10.30
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Abstract

This study was aimed to investigate the estrogenic activity of Di-(2-ethylhexyl) adipate (DEHA) using immatured type uterotrophic assay. SD rats were treated with DEHA (40, 200, 1000mg/kg/day), estradiol-3-benzoate (EB) $(1{\mu}g/kg/day)$ as positive control on the assay. In immatured-type uterotrophic assay, relative organ weights of kidney and reproductive organs such as ovary at high-dose group were significantly increased compared to those of vehicle control group. DEHA did not influence the levels of serum FSH and LH, and uterine morphological changes such as luminal epithelial height, myometrial thickness and numbers of uterine gland, and BrdU indices. In these results, there was no significant variation by DEHA treatment, suggesting that DEHA appears not to be a endocrine disrupter with estrogenic activity.

Keywords

References

  1. 식품의약품안전청 : 내분비계 장애(추정)물질 독성자료집. 141, 1999
  2. Melnick, R. L., Morrissey, R. E. and Tomaszewski, K. E. : Studies by the National Toxicology Program on di(2-ethylhexyl)phthalate. Toxicology and Industrial Health, 3(2), 99-118, 1987 https://doi.org/10.1177/074823378700300208
  3. Kim, E. J. : Study on Anti-estrogenic Activity of DEHP as an Endocrine Disruption Chemical. Korean Journal of Environmental Health, 29(2), 7-15, 2003
  4. Kim, P. G. and Yang, Y. H. : Effects of Butyl Benzyl Phthalate on Dams and F1 during Lactation Period of Rats. Korean Journal of Environmental Health, 29(2), 16-22, 2003
  5. Choi, K., Hwang, S. D., Kwon, E. and Kim, P. G. : The Reproductive Toxicity by Combined Treatment of Bisphenol A and Butyl Benzyl Phthalate During Gestation, Lactation Period in Rats. Korean Journal of Environmental Health, 30(2), 71-78, 2004
  6. Kaufmann, W., Deckardt, K., McKee, R. H., Butala, J. H. and Bahnemann, R. : Tumor induction in mouse liver: di-isononyl phthalate acts via peroxysome proliferation. Regulatory Toxicology and Pharmacology. 36(2), 175-183, 2002 https://doi.org/10.1006/rtph.2002.1575
  7. Laurence, C., Angela, J. M. and John, G. : Migration from plasticized films into foods. 4. Use of polymeric plasticizers and lower levels of di-(2-ethylhexyl adipate plasticizers in PVC films to reduce migration into food. Food Additives Contaminants, 15(3), 277-282, 1988
  8. Peterson, J. H. and Breindahl, T. : Specific migration of di-(2-ethylhexyl)adipate (DEHA) from plasticized PVC film: results from an enforcement campaign. Food Additives Contaminants, 15(5), 600-608, 1998 https://doi.org/10.1080/02652039809374687
  9. Petersen, J. H., Naamansen, E. T. and Nielsen, P. A. : PVC cling film in contact with cheese: health aspects related to global migration and specific migration of DEHA. Food Additives Contaminants, 12(2), 245-253, 1995 https://doi.org/10.1080/02652039509374299
  10. Singh, A. R., Lawrence, W. H. and Autian, J. : Dominant lethal mutations and antifertility effects of di-2-ethylhexyl adipate and diethyl adipate in male mice. Toxicology and Applied Pharmacology, 32(2), 566-576, 1975 https://doi.org/10.1016/0041-008X(75)90121-0
  11. Miyagawa, M., Takasawa, H., Sugiyama, A., Inoue, Y., Murata, T., Uno, Y. and Yohikawa, K. : The in vivo-in vitro replicative DNA synthesis (RDS) test with hepatocytes prepared from male B6C3F1 mice as an early prediction assay for putative nongenotoxic (Ames-negative) mouse hepatocarcinogens. Mutation Research, 343, 157-183, 1995 https://doi.org/10.1016/0165-1218(95)90082-9
  12. Lake, B. G., Price, R. J., Cumminghame, M. E. and Walters D. G. : Comparison of the effects of di-(2-ethylhexyl) adipate on hepatic peroxisome proliferation and cell replication in the rat and mouse. Toxicology, 123(3), 217-226, 1997 https://doi.org/10.1016/S0300-483X(97)00125-X
  13. Moody, D. E. and Reddy, J. K. : Serum triglyceride and cholesterol contents in male rats receiving diets containing plasticizers and analogues of the ester 2-ethylhexanol. Toxicology Letters, 10(4), 379-383, 1982 https://doi.org/10.1016/0378-4274(82)90233-8
  14. NTP : Carcinogenesis bioassay of di-2-ethylhexyl) adipate in F344 rats and B6C3F1 mice. National Toxicology Program Technical Report, Series No. 212, 1982
  15. Kluwe, W. M., McConnell, E. E., Huff, J. E., Haseman, J. K., Douglas, J. F. and Hartwell, W. V. : Carcinogenicity testing of phthalate esters and related compounds by the National Toxicology Program and the National Cancer Institute. Environmental Health Perspectives, 45, 129-133, 1982 https://doi.org/10.2307/3429396
  16. 환경부 : 유해화학물질관리기본계획(2001-2005). 236, 2000
  17. OECD : Validation Protocol for the Uterotrophic Assay. Task Force on Endocrine Disruptor Testing and Assessment. 1999
  18. EPA EDSTAC : Endocrine Disrupotr Screening and Testing Advisory Committee Final Report, 1998
  19. Jordan, V. C. and Gosden, B. : Differential antiestrogen action in the immature rat uterus: a comparison of hydroxylated antiestrogens with high affinity for the estrogen receptor. Journal of Steroid Biochemistry, 19(3), 1249-1258, 1983 https://doi.org/10.1016/0022-4731(83)90147-4
  20. Ashby, J., Odum, J. and Foster, J. R. : Activity of raloxifene in immature and ovariectomized rat uterotrophic assays. Regulatory Toxicology and Pharmacology, 25(3), 226-231, 1997 https://doi.org/10.1006/rtph.1997.1108
  21. Odum, J., Lefevre, P. A., Tittensor, S., Paton, D., Routledge, E. J., Beresford, N. A., Sumpter, J. P. and Ashby, J. : The rodent uterotrophic assay: critical protocol features, studies with nonyl phenols, and comparison with a yeast estrogenicity assay. Regulatory Toxicology and Pharmacology, 25(2), 176-188, 1997 https://doi.org/10.1006/rtph.1997.1100
  22. Kang, K. S., Kim, H. S., Ryu, D. Y., Che, J. H. and Lee, Y. S. : Immature uterotrophic assay is more sensitive than ovariectomized uterotrophic assay for the detection of estrogenicity of p-nonylphenol in Sprague-Dawley rats. Toxicology Letters, 20, 118(1-2), 109-115, 2000 https://doi.org/10.1016/0378-4274(84)90175-9
  23. Han, S. Y., Kim, H. S., Han, S. K., Rhee, Y., Yang, K. H. and Park, K. R. : Study on the estrogenic activity of di-(2-ethylhexyl) adipate in E-screen assay and uterotrophic assay. Korean Journal of Food Science Technology, 32(4), 964-969, 2000
  24. Lee, H. C., Yamanouchi, K. and Nishihara, M. : Effects of Perinatal Exposure to Phthalate/adipate esters on hypothalamic gene expression and sexual behavior in rats. The Journal of Reproduction and Development. 52(3), 343-52, 2006 https://doi.org/10.1262/jrd.17096
  25. Birner, P., Ritzi, M., Musahl, C., Knippers, R., Gerdes, J., Voigtlander, T., Budka, H. and Hainfellner, J. A. : Immunohistochemical detection of cell growth fraction in formalin-fixed and paraffin-embedded murine tissue. The American Journal of Pathology, 158(6), 1991-1996, 2001 https://doi.org/10.1016/S0002-9440(10)64670-6
  26. Bosq, J. and Bourhis, J. : Bromodeoxyuridine (BrdU). Analysis of cellular proliferation. $Ann{\frac{1}{4}}OE$ of Pathology, 17(3), 171-178, 1997
  27. Shin, J. H., Moon, H. J., Kim, T. S., Kang, I. H., Ki, H. Y., Choi, K. S. and Han, S. Y. : Repeated 28-day oral toxicity study of vinclozolin in rats based on the draft protocol for the 'Enhanced OECD Test Guideline No. 407' to detect endocrine effects. Archives of Toxicology, 80(9), 547-554, 2006 https://doi.org/10.1007/s00204-006-0080-6
  28. Cho, S. D., Kim, J. H., Kim, D. Y., Lee, Y. S. and Kang, K. S. : Pre-validation study for OECD enhanced test guideline 407 protocol by gavage for 4 weeks using propylthiouracil and tamoxifen. Toxicology Letters, 144(2), 195-204, 2003 https://doi.org/10.1016/S0378-4274(03)00200-5