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Evaluation of Developmental Toxicity of Amitraz in Sprague-Dawley Rats

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Abstract

This study investigated the potential adverse effects of amitraz on the initiation and maintenance of pregnancy in Sprague-Dawley rats as well as its effects on embryo–fetal development after maternal exposure during the entire pregnancy period. Amitraz was administered to pregnant rats by gavage from days 1 to 19 of gestation at dose levels of 0, 3, 10, and 30 mg/kg/day. All dams underwent a caesarean section on day 20 of gestation and their fetuses were examined for any external, visceral, and skeletal abnormalities. At 30 mg/kg, maternal toxicity manifested as an increase in the incidence of abnormal clinical signs and a lower body weight gain and food intake. Developmental toxicity included an increase in the fetal death rate, a decrease in the litter size, and a reduction in the fetal body weight. In addition, there was an increase in the incidence of fetal external, visceral, and skeletal abnormalities. At 10 mg/kg, maternal toxicity observed included a decrease in the body weight gain and a decrease in food intake. In addition, minimal developmental toxicity, including a decrease in the fetal body weight, an increase in the visceral and skeletal aberrations, and a delay in fetal ossification. There were no signs of either maternal toxicity or developmental toxicity at 3 mg/kg. These results show that amitraz administered during the entire pregnancy period in rats is embryotoxic and teratogenic at the maternally toxic dose (i.e., 30 mg/kg/day) and is minimally embryotoxic at a minimally maternally toxic dose (i.e., 10 mg/kg/day). Under these experimental conditions, the no-observed-adverse-effect level of amitraz for both dams and embryo-fetal development is estimated to be 3 mg/kg/day.

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References

  • Alkalay AL, Graham JM Jr, Pomerance JJ (1998) Evaluation of neonates born with intrauterine growth retardation: review and practice guidelines. J Pernatol 18:142–151

    CAS  Google Scholar 

  • Al-Thani RK, Al-Thani AS, Elbetieha A, Darmani H (2003) Assessment of reproductive and fertility effects of amitraz pesticide in male mice. Toxicol Lett 138:253–260

    Article  CAS  Google Scholar 

  • Aziz SA, Knowles CO (1973) Inhibition of monoamine oxidase by the pesticide chlordimeform and related compounds. Nature 242:417–418

    Article  CAS  Google Scholar 

  • Chahoud I, Buschman J, Clark R et al (1999a) Classification terms in developmental toxicology: need for harmonization. Reprod Toxicol 13:77–82

    Article  CAS  Google Scholar 

  • Chahoud I, Ligensa A, Dietzel L, Faqi AS (1999b) Correlation between maternal toxicity and embryo/fetal effects. Reprod Toxicol 13:375–381

    Article  CAS  Google Scholar 

  • Chernoff N, Rogers JM, Kavlock RJ (1989) An overview of maternal toxicity and prenatal development: considerations for developmental toxicity hazard assessments. Toxicology 59:111–125

    Article  CAS  Google Scholar 

  • Chung MK, Kim JC, Han SS (2005) Embryotoxic effects of CKD-602, a new camptothecin anticancer agent, in rats. Reprod Toxicol 20:165–173

    Article  CAS  Google Scholar 

  • Dawson AB (1926) A note on the staining of the skeleton of cleared specimens with Alizarin Red S. Stain Technol 1:123–124

    Google Scholar 

  • EPA (Environmental Protection Agency) (1987) EPA Fact Sheet No. 147 Amitraz. US EPA, Washington, DC

  • Fisher RA (1970) Statistical methods for research workers, 14th ed. Oliver and Boyd, Edinburgh

    Google Scholar 

  • Jorens PG, Zandijk E, Belmans L, Schepens PJ, Bossaert LL (1997) An unusual poisoning with the unusual pesticide amitraz. Hum Exp Toxicol 16:600–601

    Article  CAS  Google Scholar 

  • Khera KS (1987) Maternal toxicity in humans and animals: effects on fetal development and criteria for detection. Teratog Carcinog Mutagen 7:287–295

    Article  CAS  Google Scholar 

  • Kim JC, Kim SH, Shin DH et al. (2004) Effects of prenatal exposure to the environmental pollutant 2-bromopropane on embryo-fetal development in rats. Toxicology 196:77–86

    Article  CAS  Google Scholar 

  • Kim JC, Lee SJ, Bae JS, Park JI, Kim YB, Chung MK (2001) Historical control data for developmental toxicity study in Sprague-Dawley rats. J Toxicol Public Health 17:83–90

    Article  Google Scholar 

  • Kruskal WH, Wallis WA (1952) Use of ranks in one criterion variance analysis. J Am Statist Assoc 47:614–617

    Article  Google Scholar 

  • MARTA (Middle Atlantic Reproduction Teratology Association) (1997) Appendix B: Historical control data. In: Hood R.D (ed) Handboook of developmental toxicology. CRC Press, New York, pp 716–724

    Google Scholar 

  • Morita H, Ariyuki F, Inomata N et al. (1987) Spontaneous malformations in laboratory animals: frequency of external, internal and skeletal malformations in rats, rabbits and mice. Congen Anom 27:147–206

    Google Scholar 

  • Moser VC, Macphail RC (1985) Yohimbine attenuates the delayed lethality induced in mice by amitraz a formamidine pesticide. Toxicol Lett 28:99–104

    Article  CAS  Google Scholar 

  • Nishimura KA (1974) Microdissection method for detecting thoracic visceral malformations in mouse and rat fetuses. Congen Anom 14:23–40

    Google Scholar 

  • Nurminen T (1995) Maternal pesticide exposure and pregnancy outcome. J Occup Environ Med 37:935–940

    Article  CAS  Google Scholar 

  • Osano O, Oladimeji AA, Kraak MHS, Admiraal W (2002) Teratogenic effects of amitraz, 2,4-dimethylaniline, and paraquat on developing frog (Xenopus) embryos. Arch Environ Contam Toxicol 43:42–49

    Article  CAS  Google Scholar 

  • Palermo-Neto J, Florio JC, Sakate M (1994) Developmental and behavioral effects of prenatal amitraz exposure in rats. Neurotoxicol Teratol 16:65–70

    Article  CAS  Google Scholar 

  • Palermo-Neto J, Sakate M, Florio JC (1997) Developmental and behavioral effects of postnatal amitraz exposure in rats. Braz J Med Biol Res 30:989–997

    Article  CAS  Google Scholar 

  • Proudfoot AT (2003) Poisoning with amitraz. Toxicol Rev 22:71–74

    Article  CAS  Google Scholar 

  • SAS Institute, Inc (1997) SAS/STAT software: Changes and enhancements through release 6.12. SAS Institute, Cary, NC

  • Scheffe H (1953) A method of judging all contrasts in the analysis of variance. Biometika 40:87–104

    Article  Google Scholar 

  • Shin DH, Hsu WH (1994) Influence of the formamidine pesticide amitraz and its metabolites on porcine myometrial contractility—involvement of alpha (2)-adrenoceptors and Ca2+ channels. Toxicol Appl Pharmacol 128:45–49

    Article  CAS  Google Scholar 

  • Ulukaya S, Demirag K, Moral AR. (2001) Acute amitraz intoxication in human. Intensive Care Med 27:930–933

    Article  CAS  Google Scholar 

  • Vim GKW, Holsapple MP, Pfister WR, Hollingworth RM (1978) Prostaglandin synthesis inhibited by formamidine pesticides. Life Sci 23:2509–2516

    Article  Google Scholar 

  • Weil CS (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

    Article  Google Scholar 

  • Wilson JG (1965) Methods for administering agents and detecting malformations in experimental animals. In: Wilson JG, Warkany J (eds) Teratology. principles and techniques, University of Chicago Press, Chicago, pp 262–277

    Google Scholar 

  • Wise LD, Beck SL, Beltrame D et al (1997) Terminology of developmental abnormalities in common laboratory mammals (Version 1). Teratology 55:249–292

    Article  CAS  Google Scholar 

  • Yamada T, Hara M, Ohba Y, Inoue T, 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

    CAS  Google Scholar 

  • Zhang J, Cai WW, Lee DJ (1992) Occupational hazards and pregnancy outcomes. Am J Ind Med 21:397–408

    CAS  Google Scholar 

Download references

Acknowledgment

This study was financially supported by a special research fund of Chonnam National University in 2004.

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Authors and Affiliations

  1. College of Veterinary Medicine, Chonnam National University, Gwangju, 500-757, South Korea

    J. C. Kim, J. Y. Shin, Y. S. Yang, D. H. Shin, C. J. Moon & S. H. Kim

  2. College of Veterinary Medicine, Kyungpook National University, Daegu, 702-701, South Korea

    S. C. Park

  3. College of Veterinary Medicine, Chungbuk National University, Cheongju, 361-763, South Korea

    Y. B. Kim

  4. Korea Research Institute of Bioscience and Biotechnology, Daejeon, 305-333, South Korea

    H. C. Kim

  5. Korea Institute of Toxicology, KRICT, Daejeon, 305-600, South Korea

    M. K. Chung

Authors
  1. J. C. Kim
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  2. J. Y. Shin
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  3. Y. S. Yang
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  4. D. H. Shin
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  5. C. J. Moon
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  6. S. H. Kim
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  7. S. C. Park
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  8. Y. B. Kim
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  9. H. C. Kim
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  10. M. K. Chung
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Correspondence to J. C. Kim.

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Kim, J., Shin, J., Yang, Y. et al. Evaluation of Developmental Toxicity of Amitraz in Sprague-Dawley Rats. Arch Environ Contam Toxicol 52, 137–144 (2007). https://doi.org/10.1007/s00244-006-0021-7

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  • DOI: https://doi.org/10.1007/s00244-006-0021-7

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