Journal of Preventive Medicine and Public Health

The Korean Society for Preventive Medicine (대한예방의학회)
권호 표지

Developmental Toxicity by Exposure to Bisphenol A Diglycidyl Ether during Gestation and Lactation Period in Sprague-dawley Male Rats

  • Hyoung, Un-Jun (Department of Preventive Medicine, Chung-Ang University College of Medicine) ;
  • Yang, Yun-Jung (Department of Preventive Medicine, Chung-Ang University College of Medicine) ;
  • Kwon, Su-Kyoung (Department of Preventive Medicine, Chung-Ang University College of Medicine) ;
  • Yoo, Jae-Hyoung (Department of Pathology, Chung-Ang University College of Medicine) ;
  • Myoung, Soon-Chul (Department of Urology, Chung-Ang University College of Medicine) ;
  • Kim, Sae-Chul (Department of Urology, Chung-Ang University College of Medicine) ;
  • Hong, Yeon-Pyo (Department of Preventive Medicine, Chung-Ang University College of Medicine)
  • Published : 2007.03.31
Download PDF
⟨ Previous Next ⟩

Abstract

Objectives : Bisphenol A diglycidyl ether (BADGE) is the major component in commercial liquid epoxy resins, which are manufactured by co-reacting bisphenol A with epichlorohydrin. This study was performed to show the developmental effects of prenatal and postnatal exposures to BADGE in male rat offspring. Methods : Mated female rats were divided into four groups, each containing 12 rats. The dosing solutions were prepared by thoroughly mixing BADGE in corn oil at the 0, 375, 1500 and 3000 mg/kg/day concentrations. Mated females were dosed once daily by oral gavage on gestation day (GD) 6 - 20 and postnatal day (PND) 0 - 21. Pregnant female dams were observed general symptoms and body weight. Also, male pups were observed the general symptoms, body weight, developmental parameters (e.g. anogenital distance, pina detachment, incisor eruption, nipple retention, eye opening, testis descent), organ pathologic changes and hormone levels of plasma. Results : Pregnant rats treated with BADGE died at a rate of about 70% in the 1500 mg/kg/day group and all rats treated with 3000 mg/kg/day died. Body weight, for male pups treated with doses of 375 mg/kg/day, was significantly lower than in the control group at PND 42, 56, and 63 (p<0.05). Evaluation of body characteristics including; separation of auricle, eruption of incisor, separation of eyelid, nipple retention, descent of testis, and separation of the prepuce in the BADGE treated group showed no difference in comparisons with the control group. AGD and adjusted AGD (mm/kg) for general developmental items in BADGE 375 mg/kg/day treated pups tended to be longer than in controls, however, these differences were not statistically significant. Relative weights of adrenal gland, lung (p<0.05), brain, epididymis, prostate, and testis (p<0.01) were heavier than in control in measures at PND 9 weeks. There were no significant changes in comparisons of histological findings of these organs. Loss of spermatids was observed in the seminiferous tubule at PND 9 weeks, but no weight changes were observed. The plasma estrogen levels were similar in the control and treatment groups at PND 3, 6 and 9 weeks. The plasma testosterone levels in the control group tended to increase with age. However, in the BADGE 375 mg/kg/day treated male pups it did not tend to increase. Conclusions : These findings suggest that BADGE is a chemical that has developmental effects consistent with it being an endocrine disruptor.

Keywords

References

  1. Poole A, van Herwijnen P, Weideli H, Thomas MC, Ransbotyn G, Vance C. Review of the toxicology, human exposure and safety assessment for Bisphenol A Diglycidyl Ether (BADGE). Food Addit Contam 2004; 21(9): 905-919 https://doi.org/10.1080/02652030400007294
  2. Bisphenol A Diglycidyl Ether. IARC monogr eval carcinog risks hum 1999; 71 (Pt 3): 1285-1289
  3. Choi JC, Kyung SH, Lee GT, Lee KH. Simultaneous analysis method of BPA, BPF, BADGE, BFDGE and their degradation products in canned foods and food stimulants by HPLC. Kor J Food Sci Tech 2002; 34(2): 174-179 (Korean)
  4. Hammarling L, Gustavsson H, Svensson K, Oskarsson. A migration of Bisphenol A Diglycidyl Ether (BADGE) and its reaction products in canned foods. Food Addit Contam 2000; 17(11): 937-943 https://doi.org/10.1080/026520300750038126
  5. Pulgar R, Olea-Serrano MF, Novillo-Fertrell A, Rivas A, Pazos P, Pedraza V, Navajas JM, Olea N. Determination of bisphenol a and related aromatic compounds released from bis-GMA-based composites and sealants by high performance liquid chromatography. Environ Health Perspect 2000; 108(1): 21-27 https://doi.org/10.2307/3454291
  6. Lyons G. Bisphenol A: A Known Endocrine Disruptor. A WWF European Toxics Program-me Report 2000 [cited 2007 Feb]; Available from:URL:http://www.wwf.org.uk /filelibrary/pdf/bisphenola.pdf
  7. Sheehan DM, Willingham E, Gaylor D, Bergeron JM, Crews D. No threshold dose for oestradiol-induced sex reversal of turtle embryos: how little is too much? Environ Health Perspect 1999; 107(2): 155-159 https://doi.org/10.1289/ehp.99107s1155
  8. vom Saal FS, Timms BG, Montano MM, Palanza P, Thayer KA, Nagel SC, Dhar MD, Ganjam VK, Oarmigiani S, Welshons WV. Prostate enlargement in mice due to fetal exposure to low doses of estradiol or diethylstilbestrol and opposite effects at high doses. Proc Natl Acad Sci USA 1997; 94(5): 2056-2061
  9. Scientific Committee on Food (SCF). Opinion on bisphenol a diglycidyl ether (BADGE). Commission of the European Communities. 1999 [cited 2007 Feb]; Available from: URL: http://eceuropa.eu./food/fs/sc/saf/out28_en.pdf
  10. Perez P, Pulgar R, Olea-Serrano F, Villalobos M, Rivas A, Metzler M, Pedraza V, Olea N. The estrogenicity of bisphenol a-related diphenylalkanes with various substituent at the central carbon and the hydroxy groups. Environ Health Perspect 1998; 106(3): 167-174 https://doi.org/10.2307/3434318
  11. Olea N, Pulgar R, Perez P, Olea-Serrano F, Rivas A, Novillo Fertrell A, Pedraza V, Soto AM, Sonnenschein C. Estrogenicity of resin-base composites and sealants used in dentistry. Environ Health Perspect 1996; 104(3): 298-305 https://doi.org/10.2307/3432888
  12. Korea Food and Drug Administration (KFDA). Good Laboratory Practice Regulation for Nonclinical Laboratory Studies. Notification. 2000. No2000-63
  13. Watanabe S, Wang RS, Miyagawa M, Kobayashi K, Suda M, Sekiguchi S, Honma T. Short communication imbalance of testosterone level in male offspring of rats perinatally exposed to bisphenol A. Ind Health 2003; 41(4): 338-341 https://doi.org/10.2486/indhealth.41.338
  14. Hanley TR, Hagler AR, Sullivan VD, Stebins KE. DGEBPA: Two Generation Oral Gavage Study in Sprague-dawley Rats. Unpublished Report of the DOW Chemical Company. 1996
  15. Smith JA, Masters RE, Dawe IS. A Study of the Effect of TK 10490 on the Reproductive Function of one Generation in the Rat. Unpublished Report of Ciba-Giegy Ltd. Huntington Research Centre Report CB451/881081. 1989
  16. Wolf MA. Results of Dietary Feeding of 2,2'-bis[p-2,3-poxypropoxy)phenyl]-Propane to Male Rats. Unpublished Report of The Dow Chemical Company, Midland, Michigan. 1958
  17. Foster PM. Disruption of reproductive development in male rat off spring following in utero exposure to phthalate ester. Int J Androl 2006; 29(1): 140-147 https://doi.org/10.1111/j.1365-2605.2005.00563.x
  18. Swan SH, Main KM, Liu F, Stewart SL, Kruse RL, Calafat AM, Mao CS, Redmon JB, Ternand CL, Sullivan S, Teague JL, Study for future families research team. Decrease in anogenital distance among male infants with prenatal phthalate exposure. Environ Health Perspect 2005; 113(8): 1056-1061 https://doi.org/10.1289/ehp.8100
  19. Hoshino N, Iwai M, Okazaki Y. A two generation reproductive toxicity study of dicyclohexyl phthalate in rats. J Toxicol Sci 2005; 30 spec no: 79-96 https://doi.org/10.2131/jts.30.S79
  20. Kibayashi K, Miyagawa M, Wang RS, Sekiguchi S, Suda M, Honma T. Effects of in utero and lactional exposure to bisphenol A on somatic growth and anogenital distance in F1 rat offspring. Ind Health 2002; 40(4): 375-381 https://doi.org/10.2486/indhealth.40.375
  21. Honma S, Suzuki A, Buchanan DL, Katsu Y, Watanabe H, Iguichi T. Low dose effect of in utero exposure to bisphenol A and diethylstilbestrol on female mouse reproduction. Reprod Toxicol 2002; 16(2): 117-122 https://doi.org/10.1016/S0890-6238(02)00006-0
  22. Tyl RW, Myers CB, Marr MC, Thomas BF, Keimowitz AR, Brine DR, Veselica MM, Fail PA, Chang TY, Seely JC, Joiner RL, Butala JH, Dimond SS, Cagen SZ, Shiotsuka RN, Stropp GD, Waechter JM. Three-generation reproductive toxicity study of dietary bisphenol a in CD Sprague-dawley rats. Toxicol Sci 2002; 68(1): 121-146 https://doi.org/10.1093/toxsci/68.1.121
  23. Ema M, Fujii S, Furukawa M, Kiguchi M, Ikka T, Harazono A. Rat two-generation reproductive toxicity study of bisphenol A. Reprod Toxicol 2001; 15(5): 505-523 https://doi.org/10.1016/S0890-6238(01)00160-5
  24. Guillette L Jr, Crain DA. Environmental Endocrine Disrupters: An Evolutionary Perspective. New York: Taylor & Francis; 2000. p. 227
  25. Sokol RZ, Wang S, Wan YJ, Stenczyk FZ, Gentzschein E, Chapin RE. Long-term, lowdose lead exposure alters the gonadotropinreleasing hormone system in the male rat. Environ Health Perspect 2002; 110(9): 871-874 https://doi.org/10.1289/ehp.02110871
  26. Tohei A, Suda S, Taya K, Hashimoto T, Kogo H. Bisphenol A inhibits testicular functions and increases luteinizing hormone secretion in adult male rats. Exp Biol Med 2001; 226(3): 216-221 https://doi.org/10.1177/153537020122600309
  27. Saito D, Minamida G, Ozukuri K, Tani-Ishi N, Kato Y, Ozono S, Kawase T, Teranaka T, Koshika S. Effects of pubertal treatment with bisphenol A and bis-GMA on sex hormone level in male rats. Environ Sci 2003; 10(1): 55-61
  28. Crissman JW. DGEBPA: Two-generation Oral Gavage Reproduction Study in Spraguedawley Rats (Supplemental Sub-chronic Toxicity Report). Toxicology & Environmental Research and Consulting. Unpublished Report of The Dow Chemical Company, Midland, Michigan. 1997
  29. Breslin WJ, Kirk HD, Johnson KA. Dermal Teratology Probe Study of Evaluation of diglycidyl ether of bisphenol a (DGEBPA) in New Zealand white rabbits. Study ID: 6313-13. Unpublished Report of The Dow Chemical Company, Midland, Michigan. 1986
  30. Breslin WJ, Kirk HD, Johnson KA. Teratogenic evaluation of diglycidyl ether of bisphenol a (DGEBPA) in New Zealand white rabbits following dermal exposure. Fundam Appl Toxicol 1988; 10(4): 736-743 https://doi.org/10.1016/0272-0590(88)90200-X