Korean Journal of Veterinary Research (대한수의학회지)

The Korean Society of Veterinary Science (대한수의학회)
권호 표지

Embryo lethality and teratogenicity of 2-Bromopropane in the Sprague-Dawley rat

Sprague-Dawley 랫드에서 2-Bromopropane의 배자치사 및 최기형성 효과

  • Kim, Jong-Choon (College of Veterinary Medicine, Chonnam National University) ;
  • Oh, Ki-Seok (College of Veterinary Medicine, Chonnam National University) ;
  • Shin, Dong-Ho (College of Veterinary Medicine, Chonnam National University) ;
  • Kim, Sung-Ho (College of Veterinary Medicine, Chonnam National University) ;
  • Kim, Hyeon-Yeong (Industrial Chemicals Research Center, Industrial Safety and Health Research Institute, Korea Industrial Safety Corporation) ;
  • Yun, Hyo-In (College of Veterinary Medicine, Chungnam National University) ;
  • Jiang, Cheng-Zhe (Korea Institute of Toxicology, KRICT) ;
  • Heo, Jeong-Doo (Korea Institute of Toxicology, KRICT) ;
  • Chung, Moon-Koo (Korea Institute of Toxicology, KRICT)
  • 김종춘 (전남대학교 수의과대학) ;
  • 오기석 (전남대학교 수의과대학) ;
  • 신동호 (전남대학교 수의과대학) ;
  • 김성호 (전남대학교 수의과대학) ;
  • 김현영 (한국산업안전공단 산업안전보건연구원 산업화학물질연구센터) ;
  • 윤효인 (충남대학교 수의과대학) ;
  • 강성철 (한국화학연구원 부설 안전성평가연구소) ;
  • 허정두 (한국화학연구원 부설 안전성평가연구소) ;
  • 정문구 (한국화학연구원 부설 안전성평가연구소)
  • Accepted : 2003.11.18
  • Published : 2003.12.25
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Abstract

The present study was undertaken to evaluate the potential adverse effects of 2-BP on pregnant dams and embryo-fetal development after maternal exposure during the gestational days (GD) 6 through 19 in Sprague-Dawley rats. The test chemical was administered subcutaneously to pregnant rats at dose levels of 0, 375, 750 and 1250 mg/kg/day. During the test period, clinical signs, mortality, body weights and food consumption were examined. All dams were subjected to caesarean section on GD 20 and their fetuses were examined for external, visceral and skeletal abnormalities. At above 750 mg/kg, toxic effects including signs of toxicity, suppressed body weight, decreased gravid uterine weight and reduced food intake were observed in pregnant dams. An increase in the fetal deaths, a decrease in the litter size, a reduction in the fetal body weight and an increase in the incidence of fetal morphological alterations were also found. There were no adverse effects on either pregnant dams or embryo-fetal development at a dose level of 375 mg/kg. These results suggest that a 14-day subcutaneous dose of 2-BP is embryolethal and teratogenic at above 750 mg/kg/day in pregnant rats. In the present experimental condition, the no-observed-adverse-effect level of 2-BP is considered to be 375 mg/kg/day for dams and embryo-fetuses, respectively.

Keywords

References

  1. Chahoud, I., Buschmann, J., Clark, R., Druga, A., Falke, H., Faqi, A., Hansen, E., Heinrich-Hirsch, B., Hellwig, J., Lingk, W., Parkinson, M., Paumgartten, F. J., Pfeil, R., Platzek, T, Scialli, A. R., Seed, J., Stahlmann, R., Ulbrich, B., Wu, X., Yasuda, M., Younes, M. and Solecki, R. Classification terms in developmental toxicology: need for harmonisation. Report of the Second Workshop on the Terminology in Developmental Toxicology. Reprod Toxicol. 1999, 13, 77-82
  2. Chernoff, N., Rogers, J. M. and Kavlock, R. J. An overview of matemal toxicity and prenatal development: considerations for developmental toxicity hazard assessments. Toxicology. 1989, 59, 111-125
  3. Chung, M. K., Kim, J. C. and Roh, J. K. Embryotoxic effects of SKI 2053R, a new potential anticancer agent, in rats. Reprod. Toxicol. 1998, 12, 375-381
  4. Dawson, A. B. A note on the staining of the skeleton of cleared specimens with Alizahn Red S. Stain Technol. 1926, 1, 123-124
  5. Fisher, R. A. Statistical methods for research workers 14th edition, Oliver and Boyd, Edinburgh, UK. 1970
  6. Ichihara, G., Asaeda, N., Kumazawa, T., Tagawa, T., Kamijima. M., Yu, X., Kondo, H., Nakajima, T., Kitoh, J., Yu, I. J., Moon, Y. H., Hisanaga, N. and Takeuchi, Y. Testicular and haematopoietic toxicity of 2-bromopropane, a substitute for ozone layer-depleting chlorofluorocarbons. J. Occup. Health. 1997, 39, 57-63
  7. Ishikawa, H., Tian, Y. iind Yamauchi, T. Induction of micronuclei formation in preimplantation mouse embryos after matemal treatment with 2-bromopropane. Reprod. Toxicol. 2001, 15, 81-85
  8. Kang, K. S., Li, G. X., Che, J. H. and Lee, Y. S. Impairment of male rat reproductive function in Fl offspring from dams exposed to 2-bromopropane during gestation and lactation. Reprod. Toxicol. 2002, 16, 151-159
  9. Khera, K. S. Maternal toxicity in human and animals: effects on fetal development and critena for detection. Teratogen. Carcinogen. Mutagen. 1987, 7, 287-295
  10. Kim, J. C., Bae, C. S., Kirn, S. H., Yun, H. L, Park, S. C., Shin, H. C., Han, J. and Chung, M. K. Transplacental pharmacokinetics of the new fluoroquinolone DW-l16 in pregnant rats, Toxicol. Lett. 2003, 142, 103-109
  11. Kim, J. C., Lee, S. J., Bae, J. S., Park, J. L, Kim, Y. B. and Chung, M. K. Historical control data for developmental toxicity study in Sprague-Dawley rats. J. Toxicol. Public. Health. 2001, 17, 83-90
  12. Kim, J. C., Shin, D. H., Kim, S. H., Ahn, T. H., Kang, S. S., Jang, B. S., Kim, C. Y. and Chung, M. K. Developmental toxicity evaluation of the new fluoro-quinolone antibacterial DW-116 in rat. Teratogen Carcinogen. Mutagen. 2003. 23(Suppl. 1), 123-136
  13. Kim, J. C., Shin, H. C., Cha, S. W., Koh, W. S., Chung, M. K. and Han, S. S. Evaluation of developmental toxicity in rats exposed to the environmental estrogen bisphenol A during pregnancy. Life Sci. 2001, 69, 2611-2625
  14. Kim, Y., Jung, K., Hwang, T, Jung, G., Kim, H., Park, J., Kim,, J., Park, J., Park, D., Park, S., Choi, K. and Moon, Y. Hematopoietic and reproductive hazards of Korean electronic workers exposed to solvents containing 2-bromopropane. Scan. J. Work Environ. Health. 1996. 22. 387-391
  15. Kruskal, W. H. and Wallis, W. A. Use of ranks in one criterion variance analysis. J. Am. Statist. Assoc 1952, 47, 614-617
  16. Maeng, S. H. and Yu, I. J. Mutagenicity of 2-bromopropane. Ind. Health. 1997, 35, 87-95
  17. MARTA(Midd1e Atlantic Reproduction Teratology Association). Appendix B: Historical Control Data in Handbook of Developmental Toxicology (Hood, R.D. ed.), pp. 16-724, CRC Press, New York, 1997
  18. Mirkin, B. L. Maternal and fetal distribution of drugs in pregnancy, Clin. Pharmacol. Ther. 1973, 14. 643-647
  19. Nakatsuka, T., Horimoto, M., Ito, M., Matsubara, Y., Akaike, M. and Ariyuki, F. Japan pharmaceutical manufacturers association (JPMA) survey on background control data of developmental and reproductive toxicity studies in rats, rabbits and mice. Cong. Anon. 1997, 37. 47-138
  20. Nau, H. and Scott, W. J. Jr. Weak acids may act as teratogens by accumulating in the basic milieu of the early mammalian embryo. Nature. 1986, 323, 276-278
  21. Nishimura, K. A. Microdissection method for detecting thuracic visceral malformations in mouse and rat fetuses. Cong. Anom. 1974, 14, 23-40
  22. NRC (National Research Council). Guide for the Care and Use of Laboratory Animals. Natiunal Research Council. National Academy, Washington, USA, 1996
  23. Omura, M., Romero, Y., Zhao, M. and Inoue, N. Histopathologicat evidence that spermatogonia are the target cells of 2-bromopropane. Toxicol. Lett. 1999, 104, 19-26
  24. Park, J. S., Kim, Y. H., Park, D. W., Choi, K. S., Park, S. H. and Moon, Y. H. An outbreak of hematupoietic and reproductive disorders due to solvents containing 2-bromopropane in an electronic factory, South Korea: Epidemiological survey. J. Occup. Health. 1997, 39, 138-143
  25. SAS Institute Inc. SAS/STAT Software: Changes and Enhancements Through Release 6.12. SAS Institute Inc., Cary, NC, 1997
  26. Scheffe, H. A method of judging all contrasts in the analysis of variance. Biometika, 1953, 40, 87-104
  27. Son, H. Y., Kim, Y. B., Kang, B. H., Cho, S. W., Ha, C. S. and Roh, J. K. Effects of 2-bromopropane on spermatogenesis in the Sprague-Dawley rat. Reprod. Toxicol. 1999, 13, 179-187
  28. Wilson, J. G. Methods for administering agents and detecting malformations in experimental animals in Teratology. Principles and Techniques (Wilson J. G. and Warkany J. eds.), pp. 262-277, University of Chicago Press, Chicago and London, 1965
  29. Wise, L. D., Beck, S. L., Beltrame, D.. Beyer, B. K., Chahoud, I., Clark, R. L., Clark, R., Druga, A. M., Feuston, M. H., Guittin, P., Henwood, S. M., Kimmel, C. A., Lindstrom, P., Palmer, A. K., Petrere, J. A., Solomon, H. M., Yasuda, M. and York, R. G. Terminology of developmental abnormalities in common laboratory mammals (Version 1), Teratology. 1997, 55, 249-292
  30. Wu, X., Faqi, A. S., Yang, J., Pang, B. R, Ding, X., Jiang, X. and Chahoud, I. 2-Bromopropane induces DNA damage, impairs functional antioxidant cellular defenses, and enhances the lipid peroxidation process in primary cultures of rat Leydig cells. Reprod. Toxicol. 2002, 16, 379-384
  31. Yii, X., Kamijima, M., Ichihara, G., Li, W., Kitoh, J., Xie, Z., Shibata, E., Hisanaga, N. and Takeuchi, Y. 2-Bromopropane causes ovarian dysfunction by damaging primordial follicles and their oocytes in female rats. Toxicol. Appl. Pharmacol. 1999, 159, 185-193
  32. Zhao, L. X., Kim, E. K., Lim, H. T., Moon, Y. S., Kim, N. H., Kim, T. H., Choi, H., Chae, W., Jeong, T. C. and Lee, E. S. Synthesis, characterization and in vitro identification of $N_7$-guanine adduct of 2-bromo-propane. Arch. Pharm. Res. 2002, 25, 39-44