The Korean Journal of Pesticide Science (농약과학회지)

The Korean Society of Pesticide Science (한국농약과학회)
권호 표지

Toxicity Assessment and Establishment Acceptable Daily Intake of Penthiopyrad

펜티오피라드(Penthiopyrad)의 독성평가와 일일섭취허용량 설정

  • Jeong, Mi-Hye (Agro-Material Safety Evaluating Division, Department of Agro-Food Safety, National Academy of Agricultural Science, Rural Development Administration) ;
  • Hong, Soon-Sung (Agro-Material Safety Evaluating Division, Department of Agro-Food Safety, National Academy of Agricultural Science, Rural Development Administration) ;
  • Park, Kyung-Hun (Agro-Material Safety Evaluating Division, Department of Agro-Food Safety, National Academy of Agricultural Science, Rural Development Administration) ;
  • Kim, Chan-Sub (Agro-Material Safety Evaluating Division, Department of Agro-Food Safety, National Academy of Agricultural Science, Rural Development Administration) ;
  • Park, Jae-Eup (Agro-Material Safety Evaluating Division, Department of Agro-Food Safety, National Academy of Agricultural Science, Rural Development Administration) ;
  • Hong, Moo-Ki (Agro-Material Safety Evaluating Division, Department of Agro-Food Safety, National Academy of Agricultural Science, Rural Development Administration) ;
  • Im, Moo-Hyeog (Korea Food and Drug Administration) ;
  • Kim, Young-Bum (Korea Institute of Toxicology) ;
  • Han, Bum-Seok (Hoseo University GLP center) ;
  • Han, Jeung-Sul (Department of Ecological Environment Conservation, Kyungpook National University)
  • 정미혜 (농촌진흥청 국립농업과학원 농산물안전성부 농자재평가과) ;
  • 홍순성 (농촌진흥청 국립농업과학원 농산물안전성부 농자재평가과) ;
  • 박경훈 (농촌진흥청 국립농업과학원 농산물안전성부 농자재평가과) ;
  • 김찬섭 (농촌진흥청 국립농업과학원 농산물안전성부 농자재평가과) ;
  • 박재읍 (농촌진흥청 국립농업과학원 농산물안전성부 농자재평가과) ;
  • 홍무기 (농촌진흥청 국립농업과학원 농산물안전성부 농자재평가과) ;
  • 임무혁 (식품의약품안전청 식품기준과) ;
  • 김용범 (한국화학연구원 안전성평가연구소) ;
  • 한범석 (호서대학교 GLP센터) ;
  • 한증술 (경북대학교 생태환경보전)
  • Received : 2010.03.25
  • Accepted : 2010.10.27
  • Published : 2010.12.31
Download PDF
⟨ Previous Next ⟩

Abstract

Penthiopyrad is a fungicide agent in types of pyrazole which is showing the effect of prevention in fungal disease and powdery mildew. In order to register this new pesticide, reports of acute toxicity and chronic toxicity by animal study were examined to set acceptable daily intake to evaluate hazards of consumers. Acute toxicity was low in toxic, and it did not have the effect of acute dermal toxicity, acute eye irritation, or skin sensitization. As the result of the study in chronic toxicity, the common effect of chemical appeared in the liver and thyroid which was proven as a toxic effect. Two-generation reproduction toxicity, genotoxicity, and prenatal development toxicity were not proven. As the result of carcinogenic study, increase of thyiroid follicular adenoma in the rat and the frequency of liver hepatocellar adenoma in mice were also increased. However, it was decided that the threshold value on the effect in chemicals could be controlled through study liver enzyme induction. Therefore, the ADI for penthiopyrad is 0.081 mg/kg/ bw/day, based on the NOAEL of 8.10 mg/kg bw/day of twelve-months dogs study and applying an uncertainty factor of 100.

펜티오피라드에 대한 독성을 평가하고 일일섭취허용량을 설정하기 위하여 급성독성시험 등 32항목의 시험성적서를 검토하였다. 펜티오피라드는의 소변과 대변으로 24 시간이내에 대부분 배살되었다. 급성독성은 낮았으며, 안점막 자극성은 경도의 자극성을 보였고 피부자극성 및 피부감작성은 없었다. 랫드, 개 90일 및 1년 반복투여 경구독성시험에서 간에 영향이 나타났다. 랫드 2세대 번식독성시험에서 수정율, 임신율 등 번식에 영향을 나타내지 않았고, 랫드 및 토끼 기형독성시험에서 기형독성은 없었다. 복귀돌연변이시험 등 6종의 유전독성시험에서 유전독성에 대한 영향은 없었으며, 랫드 24개월 발암성시험에서 갑상선 여포세포선종, 마우스 18개월 발암성시험에서 간세포 선종 발생 빈도가 증가 되었으나 간장효소 유도 시험에서 고농도 반복투여에 의한 대사효소 유도로 발생하는 영향이므로 역치가 존재한다고 판단되어 펜티오피라드는 비발암성물질로 평가하였다, 따라서 펜티오피라드의 독성시험성적서 중 가장 낮은 최대부작용량은 개 1년 반복투여독성시험의 8.10 mg/kg bw/day으로 선정하였고 번식독성, 기형독성, 발암성 등에 대한 영향이 없으므로 안전계수를 100으로 정하여 펜티오피라드의 일일섭취허용량을 0.081 mg/kg/day로 설정하였다.

Keywords

References

  1. Arcelin, G. (2000) Acute oral toxicity study in rats. RCC Ltd. Switzerland.
  2. Arcelin, G. (2001) Acute dermal toxicity study in rats. RCC Ltd. Switzerland.
  3. Broadmeadow, A. (2008) 4-Week dermal toxicity study in the rat. Huntingdon Life Science Ltd. U.K.
  4. Curran, P. G. and DeGroot, L. J. (1991) The effect of hepatic enzyme-inducing drugs on thyroid hormones and the thyroid gland. Endocr Rev. (2):135-50.
  5. Decker, U., Weber, B., Knuppe, C. and Ullrich, A. (2001) 4 Hour acute inhalation toxicity study in rats. RCC Ltd. Switzerland.
  6. Enomoto, A. (2006) MTF-753: Carcinogenicity study in mice. The institute of environmental toxicology. Japan.
  7. Gupta, K. S., Shah, J. F., Savides, M. C. and Panthani, A. M. (2005) Metabolism of [14C]MTF-753 in rats. Ricerca Bioscience, LLC. USA.
  8. Harada, T. (2006) MTF-753: 2-Week hepatic drug-metabolizing enzyme induction and cell proliferation study in rats. The institute of environmental toxicology. Japan.
  9. Masumori, S. (2000a) Gene mutation assay with MTF-753 in mouse Lymphoma cell(MLA). Biosafety Research Center. Japan.
  10. Masumori, S. (2000b) In vivo/in vitro unscheduled DNA synthesis (UDS) assay with MTF-753 in Rat Hepatocytes. Biosafety Research Center. Japan.
  11. McClain, R. M. (1989). The significance of hepatic microsomal enzyme induction and altered thyroid function in rats: Implications for thyroid gland neoplasia. Toxicol. Pathol. 17:294-303. https://doi.org/10.1177/019262338901700206
  12. Mochizuki, H. (2005) A reverse mutation assay of PCA in bacteria. Bozo Reseach Center Inc. Japan.
  13. Nakajima, M. (2000a) Bacterial reversion assay with MTF-753. Biosafety Research Center. Japan.
  14. Nakajima, M. (2000b) Cytogenetic assay with MTF-753 in Chinese hamster lung (CHL/IU) Cells. Biosafety Research Center. Japan.
  15. Nakajima, M. (2000c) DNA repair assay (REC-assay) with MTF-753 in bacillus subtilis spores. Biosafety Research Center. Japan.
  16. Nakashima, N. (2001) MTF-753: 90-day oral (dietary) toxicity study in dog. The institute of environmental toxicology. Japan.
  17. Nakashima, N. (2002) MTF-753: 90-day oral (dietary) toxicity study in mice for dose range finding. The institute of environmental toxicology. Japan.
  18. Nakashima, N. (2006) MTF-753: Chronic oral (dietary) toxicity study in dogs. The institute of environmental toxicology. Japan.
  19. Oda, S. (2001) Acute oral toxicity study of DM-PCA in rats. Bozo Research Center Inc. Japan.
  20. Oda, S. (2005a) Acute oral toxicity study of 753-A-OH in rats. Bozo Research Center Inc. Japan.
  21. Oda, S. (2005b) Acute oral toxicity study of PAM in rats. Bozo Research Center Inc. Japan.
  22. Oda, S. (2005c) Acute oral toxicity study of PCA in rats. Bozo Research Center Inc. Japan.
  23. Patten, R. (2006a) MTF-753: Embryo toxicity study by gavage administration to han wister rats. Huntingdon Life Science Ltd. U.K.
  24. Patten, R. (2006b) MTF-753: Embryo-fetal toxicity study in the rabbit by gavage administration. Huntingdon Life Science Ltd. U.K.
  25. Rosner, E., Biedermann, K. and Weber, K. (2005) MTF-753: Subchronic 90-day toxicity study (feeding) in the rat. RCC Ltd. Switzerland.
  26. Rosner, E. and Blumbach, K. (2006a) MTF-753: 104-Week oncogenicity(feeding) study in the rat. RCC Ltd. Switzerland.
  27. Rosner, E. and Blumbach, K. (2006b) MTF-753: 52-Week oral Toxicity (feeding) study in the rat. RCC Ltd. Switzerland.
  28. Sarada, M. (2005a) A reverse mutation assay of DM-PCA in bacteria. Laboratory, BML, Inc. Japan.
  29. Sarada, M. (2005b) A reverse mutation assay of PAM in bacteria. Laboratory, BML, Inc. Japan.
  30. Sarada, M. (2006) A reverse mutation assay of 753-A-OH in bacteria. Laboratory, BML, Inc. Japan.
  31. Teramoto, S. (2005) A reproduction toxicity in rats with MTF-753. The institute of environmental toxicology. Japan.
  32. Ueda, H. (2001a) MTF-753: Dermal irritation study in rabbits. The institute of environmental toxicology. Japan.
  33. Ueda, H. (2001b) MTF-753: Eye irritation study in rabbits. The institute of environmental toxicology. Japan.
  34. Ueda, H. (2001c) MTF-753: Skin sensitization study in Guinea Pigs .-Maximization Test- The institute of environmental toxicology. Japan.
  35. Wilson, A.G., Thake, D.C., Heydens, W.E., Brewster, D.W. and Hotz, K.J. (1996) Mode of action of thyroid tumor formation in the male Long-Evans rat administered high doses of alachlor. Fundam Appl Toxicol. 33(1):16-23. https://doi.org/10.1006/faat.1996.0138
  36. 농촌진흥청 농자재관리과 (2009) 농약의 등록기준, 농약관리법령 및 고시.훈령집 (발간등록번호11-1390000-002515-01), pp. 171-178, 농촌진흥청, 대한민국.
  37. 허인회 (1993) 생체내대사, 독성학, pp. 71-123, 신일상사, 대한민국.