Toxic Impact Analysis by Exposure Duration of Dog Studies for Pesticides using in Korea

국내 사용농약의 노출 기간이 개의 독성반응에 미치는 영향 분석

  • 이제봉 (농촌진흥정 국립농업과학원) ;
  • 정미혜 (농촌진흥정 국립농업과학원) ;
  • 유아선 (농촌진흥정 국립농업과학원) ;
  • 홍순성 (농촌진흥정 국립농업과학원) ;
  • 백민경 (농촌진흥정 국립농업과학원) ;
  • 오진아 (농촌진흥정 국립농업과학원) ;
  • 박경훈 (농촌진흥정 국립농업과학원) ;
  • 임양빈 (농촌진흥정 국립농업과학원)
  • Received : 2013.11.12
  • Accepted : 2013.12.02
  • Published : 2013.12.31


Both 13-week and 1-year studies in dog were required for pesticide registration in domestic pesticide control authority. It is raising issue up whether to request 1-year dog study of pesticides using non-food crop. So at this investigation, relevant toxicity test to establish acceptable daily intake (ADI), target organs, difference of no-observed adverse-effect levels (NOAELs) in 13-week and 1-year of 166 active ingredients are analyzed. The data were evaluated to determine if the 13-week dog study and the long term studies in two rodent species (mice and rats) without 1-year dog study were sufficient for the identification of NOAELs and lowest observed adverse effect levels (LOAELs) for the derivation of ADI. Toxicity end points and dose response data from 13 week and 1-year studies were compared. The analysis showed that 68 ADIs of the 166 pesticides were established from dog studies. Major target organs of dog studies were liver in 49 cases, body weight change in 21 cases, cholinesterase inhibition in 16 cases, and alteration in hematology in 14 cases. Similarity of target organ in 13-week and 1-year was 73%. 22 of 40 pesticides had similar critical effects regardless of duration and had NOAELs within a difference of 1.5-fold of each other. For the remaining 18 pesticides, 14 items had lower NOAELs in the 1-year study than 13-week study primarily due to dose selection and spacing. In only 10% of the cases were additional toxic effects identified in the 1-year study that were not observed in the 13-week study.


Supported by : 국립농업과학원


  1. Appleman, L. M. and V. J. Feron (1986) Significance of the dog as “second animal species” in toxicity testing for establishing the lowest 'no-toxic-effect level. Journal of Applied Toxicology. 6(4):271-279.
  2. Australia APVMA (2007) Agricultural Manual of Requirements and Guidelines - Ag MORAG. Volume 3.
  3. Box, R. J. and H. Spielmann (2005) Use of the dog as nonrodent test species in the safety testing schedule associated with the registration of crop and plant protection products (pesticides): present status. Archives of Toxicology. 79(11): 615-26.
  4. DeGeorge, J., L. Meyers, M. Takahashi and J. Contrera (1999) The duration of non-rodent toxicity studies for pharmaceuticals. Toxicological Sciences 49:143-155.
  5. Doe, J. E., A. R. Boobis, A. Blacker, V. Dellarco, N. G. Doerrer, C. Franklin, J. I. Goodman, J. M. Kronenberg, R. Lewis, E. E. McConnell, T. Mercier, A. Moretto, C. Nolan, S. Padilla, W. Phang, R. Solecki, L. Tilbury, B. van Ravenzwaay and D. C. Wolf (2006) A tiered approach to systemic toxicity testing for agricultural chemical safety assessment. Crit Rev Toxicol. 36:37-68.
  6. European Commission (1994) Commission Directive 94/79/EC of 21 December 1994 amending Council Directive 91/414/EEC concerning the placing of plant protection products on the market.
  7. Gerbracht, U. and H. Spielmann (1998) The use of dogs as second species in regulatory testing of pesticides. I. Interspecies comparison. Archives of Toxicology. 72(6): 319-29.]
  8. Lee, J. B., J. S. Shin, Y. K. Park, A. S. You, S. S. Hong, G. J. Im and K. Y. Kang (2007) Establishment acceptable daily intakes (ADIs) for pesticides registered in Korea. The Korean Journal of Pesticide science 11(4):289-298.
  9. Lumley, C. E., C. Parkinson and S. R. Walker (1992) An international appraisal of the minimum duration of chronic toxicity studies. Human and Experimental Toxicology 11:155-162.
  10. MAFF (2008) Data Requirements for Supporting Registration of Pesticides, (Notification No. 12-Nouan-814724 November, 2000).
  11. Parkinson, C., C. E. Lumley and S. R. Walker (1995) The value of information generated by long-term toxicity studies in the dog for the nonclinical safety assessment of pharmaceutical compounds. Fundamental and Applied Toxicology. 25(1): 115-123.
  12. Spielmann, H. and U. Gerbracht (2001) The use of dogs as second species in regulatory testing of pesticides. Part II: Subacute, subchronic and chronic studies in the dog. Archives of Toxicology. 75(1):1-21.
  13. US EPA (2005a) A Comparison of the Results of Studies on Pesticides from 12- or 24-Month Dog Studies with Dog Studies of Shorter Duration, Karl P. Baetcke, Whang Phang, and Vicki Dellarco, Health Effects Division, Office of Pesticide Programs, 2005 at
  14. US EPA (2005b) FIFRA Scientific Advisory Panel (SAP) Meeting Minutes, May 5-6, 2005, A Set of Scientific Issues Being Considered by the Environmental Protection Agency Regarding: A Comparison of the Results of Studies on Pesticides from 1- or 2-Year Dog Studies of Shorter Duration.
  15. US EPA (2006) Length of Dog Toxicity Study(ies) that is Appropriate for Chronic RfD Determinations of Pesticide Chemicals.
  16. US/EPA (2007) Federal Register Notice - Pesticides; Data Requirements for Conventional Chemicals, Technical Amendments, and Data Requirements for Biochemical and Microbial Pesticides; Final Rules(October 26, 2007).
  17. US EPA (2013)
  18. WHO (2013) monographs/en/index.html.