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. 2000 Oct;108(10):931–935. doi: 10.1289/ehp.00108931

Disposition of orally administered 2,2-Bis(4-hydroxyphenyl)propane (Bisphenol A) in pregnant rats and the placental transfer to fetuses.

O Takahashi 1, S Oishi 1
PMCID: PMC1240124  PMID: 11049811

Abstract

We studied the disposition of bisphenol A (BPA) in pregnant female F344/DuCrj(Fischer) rats and its placental transfer to fetuses after a single oral administration of 1 g/kg BPA dissolved in propylene glycol. BPA in maternal blood, liver, and kidney reached maximal concentrations (14.7, 171, and 36 microg/g) 20 min after the administration and gradually decreased. The levels were 2-5% of the maximum 6 hr after the administration. The maximal concentration of BPA in fetuses (9 microg/g) was also attained 20 min after the administration. BPA levels then gradually reduced in a similar manner to maternal blood. These results suggest that the absorption and distribution of BPA in maternal organs and fetuses are extremely rapid and that the placenta does not act as a barrier to BPA.

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Selected References

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  1. Cagen S. Z., Waechter J. M., Jr, Dimond S. S., Breslin W. J., Butala J. H., Jekat F. W., Joiner R. L., Shiotsuka R. N., Veenstra G. E., Harris L. R. Normal reproductive organ development in CF-1 mice following prenatal exposure to bisphenol A. Toxicol Sci. 1999 Jul;50(1):36–44. doi: 10.1093/toxsci/50.1.36. [DOI] [PubMed] [Google Scholar]
  2. Cagen S. Z., Waechter J. M., Jr, Dimond S. S., Breslin W. J., Butala J. H., Jekat F. W., Joiner R. L., Shiotsuka R. N., Veenstra G. E., Harris L. R. Normal reproductive organ development in Wistar rats exposed to bisphenol A in the drinking water. Regul Toxicol Pharmacol. 1999 Oct;30(2 Pt 1):130–139. doi: 10.1006/rtph.1999.1340. [DOI] [PubMed] [Google Scholar]
  3. Fang S. C., Fallin E., Freed V. H. Maternal transfer of 14C-p,p'-DDT via placenta and milk and its metabolism in infant rats. Arch Environ Contam Toxicol. 1977;5(4):427–436. doi: 10.1007/BF02220922. [DOI] [PubMed] [Google Scholar]
  4. Fischer L. J., Weissinger J. L., Rickert D. E., Hintze K. L. Studies on the biological disposition of diethylstilbestrol in rats and humans. J Toxicol Environ Health. 1976 Mar;1(4):587–605. doi: 10.1080/15287397609529360. [DOI] [PubMed] [Google Scholar]
  5. Hill D. E., Slikker W., Jr, Helton E. D., Lipe G. W., Newport G. D., Sziszak T. J., Bailey J. R. Transplacental pharmacokinetics and metabolism of diethylstilbestrol and 17 beta-estradiol in the pregnant rhesus monkey. J Clin Endocrinol Metab. 1980 May;50(5):811–818. doi: 10.1210/jcem-50-5-811. [DOI] [PubMed] [Google Scholar]
  6. Howdeshell K. L., Hotchkiss A. K., Thayer K. A., Vandenbergh J. G., vom Saal F. S. Exposure to bisphenol A advances puberty. Nature. 1999 Oct 21;401(6755):763–764. doi: 10.1038/44517. [DOI] [PubMed] [Google Scholar]
  7. Keys D. A., Wallace D. G., Kepler T. B., Conolly R. B. Quantitative evaluation of alternative mechanisms of blood and testes disposition of di(2-ethylhexyl) phthalate and mono(2-ethylhexyl) phthalate in rats. Toxicol Sci. 1999 Jun;49(2):172–185. doi: 10.1093/toxsci/49.2.172. [DOI] [PubMed] [Google Scholar]
  8. Knaak J. B., Sullivan L. J. Metabolism of bisphenol A in the rat. Toxicol Appl Pharmacol. 1966 Mar;8(2):175–184. doi: 10.1016/s0041-008x(66)80001-7. [DOI] [PubMed] [Google Scholar]
  9. Larsen R. V., Born G. S., Kessler W. V., Shaw S. M., Van Sickel D. C. Placental transfer and teratology of pentachlorophenol in rats. Environ Lett. 1975;10(2):121–128. doi: 10.1080/00139307509435815. [DOI] [PubMed] [Google Scholar]
  10. Li X., Weber L. W., Rozman K. K. Toxicokinetics of 2,3,7,8-tetrachlorodibenzo-p-dioxin in female Sprague-Dawley rats including placental and lactational transfer to fetuses and neonates. Fundam Appl Toxicol. 1995 Aug;27(1):70–76. doi: 10.1006/faat.1995.1109. [DOI] [PubMed] [Google Scholar]
  11. Maydl R., Metzler M. Oxidative metabolites of diethylstilbestrol in the fetal Syrian golden hamster. Teratology. 1984 Dec;30(3):351–357. doi: 10.1002/tera.1420300307. [DOI] [PubMed] [Google Scholar]
  12. McLachlan J. A. Prenatal exposure to diethylstilbestrol in mice: toxicological studies. J Toxicol Environ Health. 1977 Jan;2(3):527–537. doi: 10.1080/15287397709529453. [DOI] [PubMed] [Google Scholar]
  13. Miller R. K., Heckmann M. E., McKenzie R. C. Diethylstilbestrol: placental transfer, metabolism, covalent binding and fetal distribution in the Wistar rat. J Pharmacol Exp Ther. 1982 Feb;220(2):358–365. [PubMed] [Google Scholar]
  14. Morrissey R. E., George J. D., Price C. J., Tyl R. W., Marr M. C., Kimmel C. A. The developmental toxicity of bisphenol A in rats and mice. Fundam Appl Toxicol. 1987 May;8(4):571–582. doi: 10.1016/0272-0590(87)90142-4. [DOI] [PubMed] [Google Scholar]
  15. Morse D. C., Wehler E. K., van de Pas M., de Bie A. T., van Bladeren P. J., Brouwer A. Metabolism and biochemical effects of 3,3',4,4'-tetrachlorobiphenyl in pregnant and fetal rats. Chem Biol Interact. 1995 Mar 30;95(1-2):41–56. doi: 10.1016/0009-2797(94)03347-1. [DOI] [PubMed] [Google Scholar]
  16. Nagel S. C., vom Saal F. S., Thayer K. A., Dhar M. G., Boechler M., 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. Environ Health Perspect. 1997 Jan;105(1):70–76. doi: 10.1289/ehp.9710570. [DOI] [PMC free article] [PubMed] [Google Scholar]
  17. Payan J. P., Saillenfait A. M., Bonnet P., Fabry J. P., Langonne I., Sabate J. P. Assessment of the developmental toxicity and placental transfer of 1,2-dichloroethane in rats. Fundam Appl Toxicol. 1995 Dec;28(2):187–198. doi: 10.1006/faat.1995.1159. [DOI] [PubMed] [Google Scholar]
  18. Saillenfait A. M., Payan J. P., Beydon D., Fabry J. P., Langonne I., Sabate J. P., Gallissot F. Assessment of the developmental toxicity, metabolism, and placental transfer of N,N-dimethylformamide administered to pregnant rats. Fundam Appl Toxicol. 1997 Sep;39(1):33–43. doi: 10.1006/faat.1997.2343. [DOI] [PubMed] [Google Scholar]
  19. Saillenfait A. M., Payan J. P., Fabry J. P., Beydon D., Langonne I., Gallissot F., Sabate J. P. Assessment of the developmental toxicity, metabolism, and placental transfer of Di-n-butyl phthalate administered to pregnant rats. Toxicol Sci. 1998 Oct;45(2):212–224. doi: 10.1006/toxs.1998.2518. [DOI] [PubMed] [Google Scholar]
  20. Saillenfait A. M., Payan J. P., Langonné I., Gallissot F., Sabaté J. P., Beydon D., Fabry J. P. Assessment of the developmental toxicity and placental transfer of 1,2-diethylbenzene in rats. Food Chem Toxicol. 1999 Nov;37(11):1089–1096. doi: 10.1016/s0278-6915(99)00105-2. [DOI] [PubMed] [Google Scholar]
  21. Shah H. C., McLachlan J. A. The fate of diethylstilbestrol in the pregnant mouse. J Pharmacol Exp Ther. 1976 Jun;197(3):687–696. [PubMed] [Google Scholar]
  22. Sinjari T., Klasson-Wehler E., Hovander L., Darnerud P. O. Hydroxylated polychlorinated biphenyls: distribution in the pregnant mouse. Xenobiotica. 1998 Jan;28(1):31–40. doi: 10.1080/004982598239731. [DOI] [PubMed] [Google Scholar]
  23. Steinmetz R., Mitchner N. A., Grant A., Allen D. L., Bigsby R. M., Ben-Jonathan N. The xenoestrogen bisphenol A induces growth, differentiation, and c-fos gene expression in the female reproductive tract. Endocrinology. 1998 Jun;139(6):2741–2747. doi: 10.1210/endo.139.6.6027. [DOI] [PubMed] [Google Scholar]
  24. Varma D. R. Modification of transplacental distribution of salicylate in rats by acidosis and alkalosis. Br J Pharmacol. 1988 Apr;93(4):978–984. doi: 10.1111/j.1476-5381.1988.tb11488.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  25. Yamaoka K., Nakagawa T., Uno T. Statistical moments in pharmacokinetics. J Pharmacokinet Biopharm. 1978 Dec;6(6):547–558. doi: 10.1007/BF01062109. [DOI] [PubMed] [Google Scholar]
  26. Yoneyama M., Ogata A., Fujii T., Hiraga K. The maternal-foetal distribution of thiabendazole administered in two different vehicles to pregnant mice. Food Chem Toxicol. 1984 Sep;22(9):731–735. doi: 10.1016/0278-6915(84)90201-1. [DOI] [PubMed] [Google Scholar]
  27. You L., Gazi E., Archibeque-Engle S., Casanova M., Conolly R. B., Heck H. A. Transplacental and lactational transfer of p,p'-DDE in Sprague-Dawley rats. Toxicol Appl Pharmacol. 1999 Jun 1;157(2):134–144. doi: 10.1006/taap.1999.8673. [DOI] [PubMed] [Google Scholar]
  28. vom Saal F. S., Cooke P. S., Buchanan D. L., Palanza P., Thayer K. A., Nagel S. C., Parmigiani S., Welshons W. V. A physiologically based approach to the study of bisphenol A and other estrogenic chemicals on the size of reproductive organs, daily sperm production, and behavior. Toxicol Ind Health. 1998 Jan-Apr;14(1-2):239–260. doi: 10.1177/074823379801400115. [DOI] [PubMed] [Google Scholar]

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