Time-course response of epichlorohydrin on epididymal histopathology in rats

  • Kim, Kang-Hyeon (Animal Medical Center, College of Veterinary Medicine, Chonnam National University) ;
  • Shin, In-Sik (Animal Medical Center, College of Veterinary Medicine, Chonnam National University) ;
  • Lim, Jeong-Hyeon (Animal Medical Center, College of Veterinary Medicine, Chonnam National University) ;
  • Kim, Sung-Hwan (Animal Medical Center, College of Veterinary Medicine, Chonnam National University) ;
  • Park, Na-Hyeong (Animal Medical Center, College of Veterinary Medicine, Chonnam National University) ;
  • Moon, Changjong (Animal Medical Center, College of Veterinary Medicine, Chonnam National University) ;
  • Kim, Sung-Ho (Animal Medical Center, College of Veterinary Medicine, Chonnam National University) ;
  • Shin, Dong-Ho (Animal Medical Center, College of Veterinary Medicine, Chonnam National University) ;
  • Kim, Jong-Choon (Animal Medical Center, College of Veterinary Medicine, Chonnam National University)
  • Accepted : 2009.12.14
  • Published : 2009.12.31

Abstract

This research aimed to investigate the time-course effect of epichlorohydrin (ECH) on epididymal histopathology in Sprague-Dawley rats. Twenty-four male rats were randomly assigned to four groups with 6 rats in each group and were administered a single oral dose of ECH (70 mg/kg) or its vehicle. Six animals each were sacrificed on days 0 (control), 1, 2, and 7 after treatment. During the study period, clinical signs, body weights, reproductive organ weights, testicular spermatid count, epididymal sperm count, motility and morphology, and histopathology were examined. No treatmentrelated effects on body weights and reproductive organ weights were noted at any time point. On the contrary, sperm motility decreased slightly on days 1 and 2 after treatment and then decreased significantly on day 7 after treatment. The first signs of histological changes were the appearance of cell debris in the ducts and vacuolization of the epithelial cells observed in the proximal caput epididymis on day 1 after treatment. The incidences and grades of the histological changes including cell debris in the ducts, epithelial vacuolization, oligospermia, and epithelial disruption increased on day 2 and then decreased slightly on day 7 after treatment. These results show that a single oral dose of 70 mg/kg ECH to male rats results in cell debris in the ducts and vacuolization of the epithelial cells in the proximal caput epididymis, followed by reversible oligospermia, epithelial disruption, and decreased sperm motility.

Keywords

References

  1. Cassidy SL, Dix KM, Jenkins T. Evaluation of a testicular sperm head counting technique using rats exposed to dimethoxyethyl phthalate (DMEP), glycerol alpha-monochlorohydrin (GMCH), epichlorohydrin (ECH), formaldehyde (FA), or methyl methanesulphonate (MMS). Arch Toxicol 1983, 53, 71-78 https://doi.org/10.1007/BF01460003
  2. Chung MK, Han SS, Kim JC. Evaluation of the toxic potentials of a new camptothecin anticancer agent CKD-602 on fertility and early embryonic development in rats. Regul Toxicol Pharmacol 2006, 45, 273-281 https://doi.org/10.1016/j.yrtph.2006.05.004
  3. Cooper ERA, Jones AR, Jackson H. Effects of achlorohydrin and related compounds on the reproductive organs and fertility of the male rat. J Reprod Fertil 1974, 38, 379-386 https://doi.org/10.1530/jrf.0.0380379
  4. Dunnett CW. New tables for multiple comparisons with a control. Biometrics 1964, 20, 482-491 https://doi.org/10.2307/2528490
  5. Fisher R.A. Statistical Methods for Research Workers. 14th ed. p. 362, Oliver & Boyd, Edinburgh, 1970
  6. Gage JC. The toxicity of epichlorohydrin vapour. Br J Ind Med 1959, 16, 11-14
  7. Gingell R, Mitschke HR, Dzidic I, Beatty PW, Sawin VL, Page AC. Disposition and metabolism of [2-14C] epichlorohydrin after oral administration to rats. Drug Metab Dispos 1985, 13, 333-341
  8. Giri AK. Genetic toxicology of epichlorohydrin: a review. Mutat Res 1997, 386, 25-38 https://doi.org/10.1016/S1383-5742(96)00042-7
  9. Hahn JD. Post-testicular antifertility effects of epichlorohydrin and 2,3-epoxypropanol. Nature 1970, 226, 87
  10. Jelks K, Berger T, Horner C, Miller MG. $\alpha$-Chlorohydrin induced changes in sperm fertilizing ability in the rat: association with diminished sperm ATP levels and motility. Reprod Toxicol 2001, 15, 11-20 https://doi.org/10.1016/S0890-6238(00)00115-5
  11. Jelks KB, Miller MG. Alpha-chlorohydrin inhibits glyceraldehyde-3-phosphate dehydrogenase in multiple organs as well as in sperm. Toxicol Sci 2001, 62, 115-123 https://doi.org/10.1093/toxsci/62.1.115
  12. John JA, Quast JF, Murray FJ, Calhoun LG, Staples RE. Inhalation toxicity of epichlorohydrin: effects on fertility in rats and rabbits. Toxicol Appl Pharmacol 1983, 68, 415-423 https://doi.org/10.1016/0041-008X(83)90286-7
  13. Kim JC, Kim KH, Chung MK. Testicular cytotoxicity of DA-125, a new anthracycline anticancer agent, in rats. Reprod Toxicol 1999, 13, 391-397 https://doi.org/10.1016/S0890-6238(99)00028-3
  14. Kremneva SN, Tolgskaja MS. The toxicology of epichlorohydrin. Toksikol Nov Prom Him Veshchestv 1961, 2, 28-41
  15. Kruskal WH, Wallis WA. Use of ranks in one criterion variance analysis. J Am Stat Assoc 1952, 47, 583-621 https://doi.org/10.2307/2280779
  16. Laskin S, Sellakumar AR, Kuschner M, Nelson N, La Mendola S, Rusch GM, Katz GV, Dulak NC, Albert RE. Inhalation carcinogenicity of epichlorohydrin in noninbred Sprague-Dawley rats. J Natl Cancer Inst 1980, 65, 751-757 https://doi.org/10.1093/jnci/65.4.751
  17. Slott VL, Suarez JD, Simmons JE, Perreault SD. Acute inhalation exposure to epichlorohydrin transiently decreases rat sperm velocity. Fundam Appl Toxicol 1990, 15, 597-606 https://doi.org/10.1016/0272-0590(90)90044-K
  18. SRI. Chemical Economics Handbook Product Review Abstract: Epichlorohydrin. pp. 5-6, SRI Consulting, California, 2004
  19. Toth GP, Stober JA, Zenick H, Read EJ, Christ SA, Smith MK. Correlation of sperm motion parameters with fertility in rats treated subchronically with epichlorohydrin. J Androl 1991, 12, 54-61
  20. Toth GP, Zenick H, Smith MK. Effects of epichlorohydrin on male and female reproduction in Long-Evans rats. Fundam Appl Toxicol 1989, 13, 16-25 https://doi.org/10.1016/0272-0590(89)90303-5