Journal of Environmental Health Sciences (한국환경보건학회지)

Korean Society of Environmental Health (한국환경보건학회)
권호 표지

The Reproductive Toxicity by Combined Treatment of Bisphenol A and Butyl Benzyl Phthalate During Gestation, Lactation Period in Rats

Bisphenol A와 butyl benzyl phthalate 동시투여가 임신랫드와 차산자에 미치는 영향

  • 최경호 (서울대학교 보건대학원) ;
  • 황성희 (서울대학교 보건대학원, 용인대학교 환경보건학) ;
  • 권은아 (서울대학교병원 임상의학연구) ;
  • 김판기 (용인대학교 환경보건학과)
  • Published : 2004.06.01
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Abstract

This study was performed to evaluate developmental and estrogenic activity of bisphenol A (BPA) and butyl benzyl phthalate (BBP) to the second generation of Sprague-Dawley rats ingested during gestational or lactational periods. Rats were given BPA 20$\mu\textrm{g}$/kg BBP 100mg/kg of pregnancy or lactation periods. Maternal body weight and neonatal body weight were recorded. The rats were sacrificed on day 21 after birth. Reproductive organs of dam and neonate were utilized for receptor binding assay. The plasma concentrations of BPA and MBep, one of the major metabolites of BBP were analyzed with HPLC. The co-administration of BPA and BBP induced slow weight gain compared with single administration in dams. Also, such mixture induced low neonatal body weights in next generation. The dams treated with BPA and BBP during lactational periods showed significant organ weight changes in liver and spleen. The dams exposed during lactational periods showed significant organ weight changes not only in liver and spleen but also in kidney, uterus and ovary. The F1 female rats exposed during lactation periods showed significant organ weight changes in liver, spleen, ovary. The F1 male rats showed significant organ weight changes in liver, kidney, epididymis, vesicular glands, prostate. However, no clear synergistic effects of BPA and BBP were noted. There was no significantly different ER$\alpha$ expression pattern between control and treated groups. However, ER$\alpha$ expression were increased in F1 male testis and female uterus. PI male showed distinct ER$\alpha$ expression, especially in the group of lactational combined exposure. Synergistic ER$\alpha$ expression was found by combined treatment of BPA and BBP. We could not find any evidences of synergistic effects on BPA and/or BBP combined administration on dams and their fetuses, except in ER$\alpha$ expression of F1 male.

Keywords

References

  1. Olea, N., Pulgar, R., Perez, P,, Oler-Serrano, F, Rivas, A., Novillo-FertreIl, A., Pedraza, V, Soto, A. M. and C. : Sonnenschein. Estrogenicity of resin-based com posites and sealants used in dentistry. Environ. Heatth Perspect, 104, 298-305, 1996 https://doi.org/10.2307/3432888
  2. Krishnan, A. V., Starhis, P., Permiith, S. F, Tokes, L. and Feldman, D. : Bisphenlol-A: an estrogenic sub-stance is released from polycarbonate flasks during autoclaving. Endocrinotogy, 132, 2279-2286, 1993 https://doi.org/10.1210/en.132.6.2279
  3. Nagel, S. C., Vom Saal, F. S., Thayer, K. A., Dhar, M. G., Boechler, M. and Welshons, W. V. : Relative binding affinity-serum modified access (RBA-SMA) assay predicts the relative in vivo bioactivity of the xenoestrogens bisphenol A and octylphenol. Erwimn. Heatth Perspect., 105(1), 70-76, 1997 https://doi.org/10.2307/3433065
  4. Brotons, J. A., Olea, S. M. P., Villalobos, M.,Pedraza, V. and Olea, N.: Xenoestrogens released from lacquer coatings in food cans. Environ. Heatth Perspect., 103(6), 608-12, 1995 https://doi.org/10.2307/3432439
  5. Biedermann, M., Grob, K., Bronz, M., Curcio, R., Huber, M. and Lopez, F. F. : Bisphenol-A-diglycidyl ether (BADGE) in edible-oil-containing canned foods. Detenninadon by LC-LC-fluorescence detecdon. Mitt. Geb. Lebensmittelunters. Hyg., 87(5), 547-558, 1996
  6. Knshnan, A. V., Stathis, P., Pennuth, S. F., Toker, L. and Feldman, D.: Bisphenol A: An estrogenic sub-stance is released from polycarbonate flasks during autoclaving. Endocrimhgy, 132(6), 2279-2286, 1993
  7. Page, B. D. and Lacroix, G. M.: Studies into the transfer and migration of phthalate esters from alu-minium foil-paper laminates to butter and maganne. Food. Addit. Contam., 9, 197-212, 1992 https://doi.org/10.1080/02652039209374064
  8. Sharpe, R. M. and Fisher, J. S.: Gestational and lac-tational exposure of rats to xenoestrogens results in reduced testicular size and sperm production. Environ. Heatth Perspect., 103, 1136-1143, 1995 https://doi.org/10.2307/3432610
  9. Kozumbo, W. J., Kroll, R. and Rubin, R. J.: Assess-ment of the mutagenicity of phthalate esters. Envi-ron. HeaIth Perspect., 45, 103, 1982 https://doi.org/10.2307/3429391
  10. Jobling, S., Reynolds, T., White, R., Parker, M. G. and Sumpter, J. P.: A variety of environmentally persistent chemicals, including some phthalate plas-ticizers, are weakly estrogenic. Environ. Health Per-spect., 103, 582-7, 1995 https://doi.org/10.2307/3432434
  11. Eigenberg, D. A., Haig, P. B., Dean, E. C. and Glenn, S.: Distribution, excretion and metabolism of butyl benzyl phthalate in rats. J. Toxicol. Environ. Heatth, 17: 445-456, 1986 https://doi.org/10.1080/15287398609530839
  12. Ema, M., Harazono, A., Miyawaki, E. and Ogawa, Y.: Embryolethality following maternal exposure to dibutyl phthalate during early pregnancy in rats. B. Environ. Contam. Tox., 58, 636-643, 1997 https://doi.org/10.1007/s001289900381
  13. Harris, E. L. V. and Angel, S.: Protein purification methods; a practical approach. IRL Press, 16-17, 1989
  14. NIOSH. NIOSH manual of analytical methods, 3rd ed. U.S. Department of Health and Human Service, 1984
  15. Hayes, W.: Principles and methods of toxicology. 3rd ed. 989-1037, Raven Press, New York, 1994
  16. Muramatsu, M. : Agonistic effect of tamoxifen is dependent on cell type, ERE-promoter context and estrogen receptor subtype-functional difference between estrogen receptors alpha and beta. Biochem. Bioph. Res. Co., 236(1), 140-145, 1997 https://doi.org/10.1006/bbrc.1997.6915
  17. EU Document No.7, 1994
  18. Mmntaz, M. M., Knauf, L. A., Reisman, D. J., Peirano, W. B., DeRosa, C. T., Gombar, V. K., Enslein, K.,Carter, J.R. and Blake, B. W. : Assessment of effect levels of chemicals from quantitative structure-activity relationship (QSAR) models. I. Chronic lowest-observed-adverse-effect level (LOAEL). Toxicol. Lett., 79(1-3), 131-43, 1995 https://doi.org/10.1016/0378-4274(95)03365-R
  19. Gustaffsson, J. A.: Estrogen receptor $\beta$- a newdimension in estrogen mechanism of action. J. Endo-crinotogy, 163, 379-383, 1999 https://doi.org/10.1677/joe.0.1630379
  20. Gould, J. C., Leonard, L. S., Maness, S. C., Wagner, B. L., Conner, K., Zacharewski, T., Safe, S., McDonnell, D. P. and Gaido, K. W. : Bisphenol A interacts with the estrogen receptor $\alpha$ in a distinct manner from estradiol. Mol. CelI. Endocrinotogy, 142, 203-214, 1998