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Reproductive and Developmental Toxicity of Amitraz in Sprague-Dawley Rats

  • 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) ;
  • Kim, Kang-Hyeon (Animal Medical Center, College of Veterinary Medicine, Chonnam National University) ;
  • Park, Na-Hyeong (Animal Medical Center, College of Veterinary Medicine, Chonnam National University) ;
  • Shin, In-Sik (Animal Medical Center, College of Veterinary Medicine, Chonnam National University) ;
  • Moon, Chang-Jong (Animal Medical Center, College of Veterinary Medicine, Chonnam National University) ;
  • Park, Soo-Hyun (Animal Medical Center, College of Veterinary Medicine, Chonnam National University) ;
  • Kim, Sung-Ho (Animal Medical Center, College of Veterinary Medicine, Chonnam National University) ;
  • Kim, Jong-Choon (Animal Medical Center, College of Veterinary Medicine, Chonnam National University)
  • 발행 : 2010.03.04

초록

The present study was conducted to obtain information on the effects of amitraz on reproductive and developmental parameters in rats. The test chemical was administered via the drinking water containing 0, 40, 120, and 360 ppm to male rats from 2 weeks before mating to the end of 14-day mating period and to females from 2 weeks before mating, throughout mating, gestation and up to lactational day 4. During the study period, clinical signs, body weights, food intake, organ weights, reproductive and littering findings, necropsy findings, sperm parameters, and histopathology were examined. At 360 ppm, decreases in the body weight gain, food consumption, and the number of live pups and an increase in the post-implantation loss were observed. In addition, decreases in the seminal vesicle weight and sperm motility were found in males. At 120 ppm, a decrease in the food consumption was found transiently in both males and females, but no reproductive and developmental toxicity was observed in both sexes. There were no signs of either general or reproductive and developmental toxicity in the 40 ppm group. Based on these results, it was concluded that the repeated oral administration of amitraz to rats resulted in a decrease in the food consumption at 120 ppm and decreases in the seminal vesicle weight, sperm motility, and the number of live pups and an increase in the post-implantation loss at 360 ppm in rats. Under these experimental conditions, the no-observed-adverse-effect level (NOAEL) of amitraz for general and reproduction/developmental toxicity was believed to be 120 ppm, and the no-observed-effect level (NOEL) of amitraz was believed to be 40 ppm in rats.

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참고문헌

  1. Al-Thani, R.K., Al-Thani, A.S., Elbetieha, A. and Darmani, H. (2003). Assessment of reproductive and fertility effects of amitraz pesticide in male mice. Toxicol. Lett., 138, 253-260. https://doi.org/10.1016/S0378-4274(02)00418-6
  2. Andersen, H., Larsen, S., Spliid, H. and Christensen, N.D. (1999). Multivariate statistical analysis of organ weights in toxicity studies. Toxicology, 136, 67-77. https://doi.org/10.1016/S0300-483X(99)00056-6
  3. Bailey, S.A., Zidell, R.H. and Perry, R.W. (2004). Relationships between organ weight and body/brain weight in the rat: what is the best analytical endpoint? Toxicol. Pathol., 32, 448-466. https://doi.org/10.1080/01926230490465874
  4. Boorman, G.A., Eustis, S.L., Elwell, M.R., Montgomery Jr, C.A. and Mackenzie, W.F. (1990). Pathology of the Fischer Rat. Reference and Atlas. Academic Press, San Diego.
  5. Chung, M.K., Kim, J.C. and Han, S.S. (2005). Embryotoxic effects of CKD-602, a new camptothecin anticancer agent, in rats. Reprod. Toxicol., 20, 165-173. https://doi.org/10.1016/j.reprotox.2005.01.004
  6. Cooper, R.L., Goldman, J.M. and Stocker, T.E. (1999). Neuroendocrine and reproductive effects of contemporary-use pesticides. Toxicol. Ind. Health, 15, 26-36. https://doi.org/10.1177/074823379901500104
  7. Cullen, L.K. and Reynoldson, J.A. (1987). Cardiovascular and respiratory effects of the acaricide amitraz. J. Vet. Pharmacol. Ther., 10, 134-143. https://doi.org/10.1111/j.1365-2885.1987.tb00090.x
  8. Dunnett, C.W. (1964). New tables for multiple comparisons with a control. Biometrics, 20, 482-491. https://doi.org/10.2307/2528490
  9. Fisher, R.A. (1958). Statistical methods for research workers. 13th edition, (Oliver and Boyd, eds), Edinburgh, UK.
  10. Goldman, J.M., Cooper, R.L., Edwards, T.L., Rehnberg, G.L., McElroy, W.K. and Hein, J.F. (1991). Suppression of the luteinizing hormone surge by chlordimeform in ovarictomized, steroid- primed female rats. Pharmacol. Toxicol., 68, 131-136. https://doi.org/10.1111/j.1600-0773.1991.tb02050.x
  11. Goldman, J.M., Cooper, R.L., Rehnberg, G.L., Edwards, T.L., McElroy, W.K. and Hein, J.F. (1990). Chlordimeform induced alterations in endocrine regulation within the male rat reproductive system. Toxicol. Appl. Pharmacol., 104, 25-35. https://doi.org/10.1016/0041-008X(90)90279-4
  12. Greaves, P. (1990). Histopathology of Preclinical Studies: Interpretation and Relevance in Drug Evaluation. Elsevier, New York.
  13. Haschek, W.M. and Rousseaux, C.G. (1998). Fundamentals of Toxicologic Pathology. Academic Press, San Diego.
  14. Kim, J.C., Kim, K.H. and Chung, M.K. (1999). Testicular cytotoxicity of DA-125, a new anthracycline anticancer agent, in rats. Reprod. Toxicol., 13, 391-397. https://doi.org/10.1016/S0890-6238(99)00028-3
  15. Jorens, P.G., Zandijk, E., Belmans, L., Schepens, P.J. and Bossaert, L.L. (1997). An unusual poisoning with the unusual pesticide amitraz. Hum. Exp. Toxicol., 16, 600-601. https://doi.org/10.1177/096032719701601008
  16. Kim, J.C., Shin, J.Y., Yang, Y.S., Shin, D.H., Moon, C.J., Kim, S.H., Park, S.C., Kim, Y.B., Kim, H.C. and Chung, M.K. (2006). Evaulation of deveolopmental toxicity of amitraz in Sprague-Dawley rats. Arch. Environ. Contam. Toxicol., 52, 137-144.
  17. Kim, J.C., Lee, S.J., Bae, J.S., Park, J.I., Kim, Y.B. and Chung, M.K. (2001). Historical control data for developmental toxicity study in Sprague-Dawley rats. J. Toxicol. Public Health, 17, 83-90.
  18. Kruskal, W.H. and Wallis, W.A. (1952). Use of ranks in one criterion variance analysis. J. Am. Statist. Assoc., 47, 614-617.
  19. Leung, V.K., Chan, T.Y. and Yeung, V.T. (1999). Amitraz poisoning in humans. J. Toxicol. Clin. Toxicol., 37, 513-514. https://doi.org/10.1081/CLT-100102523
  20. MARTA (Middle Atlantic Reproduction Teratology Association). (1997). Appendix B: Historical Control Data. In: Hood, R.D., editor. Handboook of Developmental Toxicology. New York: CRC Press, pp. 716-724.
  21. Morita, H., Ariyuki, F., Inomata, N., Nishimura, K., Kasegawa, Y., Miyamoto, M. and Watanabe, T. (1987). Spontaneous malformations in laboratory animals: frequency of external, internal and skeletal malformations in rats, rabbits and mice. Cong. Anom., 27, 147-206. https://doi.org/10.1111/j.1741-4520.1987.tb00703.x
  22. OECD (Organization for Economic Cooperation and Development). (1995). Guideline 421: Reproduction/Developmental Screening Test, Available online from http://www.oecd.org/ehs/ test/health.htm.
  23. Palermo-Neto, J., Florio, J.C. and Sakate, M. (1994). Developmental and behavioral effects of prenatal amitraz exposure in rats. Neurotoxicol. Teratol., 16, 65-70. https://doi.org/10.1016/0892-0362(94)90010-8
  24. Palermo-Neto, J., Sakate, M. and Florio, J.C. (1997). Developmental and behavioral effects of postnatal amitraz exposure in rats. Braz. J. Med. Biol. Res., 30, 989-997. https://doi.org/10.1590/S0100-879X1997000800013
  25. Proudfoot, A.T. (2003). Poisoning with amitraz. Toxicol. Rev., 22, 71-74. https://doi.org/10.2165/00139709-200322020-00001
  26. Scheffe, H. (1953). A method of judging all contrasts in the analysis of variance. Biometika, 40, 87-104.
  27. Shin, D.H. and Hsu, W.H. (1994). Influence of the formamidine pesticide amitraz and its metabolites on porcine myometrial contractilityinvolvement of alpha (2)-adrenoceptors and Ca2+ channels. Toxicol. Appl. Pharmacol., 128, 45-49. https://doi.org/10.1006/taap.1994.1178
  28. Ulukaya, S., Demirag, K. and Moral, A.R. (2001). Acute amitraz intoxication in human. Intensive Care Med., 27, 930-933. https://doi.org/10.1007/s001340100934
  29. US Environmental Protection Agency. (1987). EPA Fact Sheet No. 14 Amitraz. U. S. EPA. Washington, USA.
  30. Weil, C.S. (1970). Selection of the valid number of sampling units and a consideration of their combination in toxicological studies involving reproduction, teratogenesis or carcinogenesis. Food Cosmet. Toxicol., 8, 77-182.
  31. Yamada, T., Hara, M., Ohba, Y., Inoue, T. and Ohno, H. (1985). Studies on implantation traces in rats. II. Staining of cleared uteri, formation and distribution of implantation traces. Exp. Anim., 34, 249-260. https://doi.org/10.1538/expanim1978.34.3_249

피인용 문헌

  1. Molecular Mechanisms of Amitraz Mammalian Toxicity: A Comprehensive Review of Existing Data vol.28, pp.6, 2015, https://doi.org/10.1021/tx500534x