Journal of Food Hygiene and Safety (한국식품위생안전성학회지)

The Korean Society of Food Hygiene and Safety (한국식품위생안전성학회)
권호 표지

Determination of Urinary Metabolites of Methidathion after Oral Administration and Dermal Application to Rats

흰쥐를 이용한 Methidathion의 경구투여 및 피부도포 후 뇨 중 대사물질 측정

  • Min, Kyung-Jin (Department of Public Health, Keimyung University) ;
  • Kim, Hwa-Sun (Department of Public Health, Keimyung University) ;
  • Cha, Chun-Geun (Department of Public Health, Keimyung University)
  • 민경진 (계명대학교 공중보건학과) ;
  • 김화선 (계명대학교 공중보건학과) ;
  • 차춘근 (계명대학교 공중보건학과)
  • Published : 2003.09.01
Download PDF
⟨ Previous Next ⟩

Abstract

This study was performed to determine the urinary metabolites of methidathion in rats. Urine samples were collected for 24 hours in metabolic cages following after oral administration and dermal application of methidation to rats. The urinary metabolites were identified by GC/MS and the excretion time courses of urinary dialkyl phosphate metabolites were analyzed by CG/FPD. The results obtained are summarized as follows: Three dialkyl phosphate metabolites, DMP, DMTP. and DMDTP, were detected in the rat urine. Urinary dialkyl phosphate metabolites were identified on the basis of their mass spectra by GC/MS. The molecular ions of DMP, DMTP,and DMDTP, were identified at m/z 198, and m/z 158, respectively. A comparison of excretion time courses of urinary dialkyl phosphate metabolites between the orally administrated and dermally applicated rats were also established, After oral administration, 79.2% of DMP, 93.9% of DMTP, and 83.0% of DMDTP were excreted into the urine by 12, 24, and 12 hours, respectively. After dermal application, 71.1% of DMP, 82.8% of DMTP 87.7% of DMDTP were excreted into the urine by 24, 48, 48 hours, respectively. Consequently, almost all of the dialkyl phosphates in oral administration were excreted within 48 hours. However, the metabolites in dermal application were excreted up to 168 hours. In the study, three urinary metabolites of methidation, DMP, DMTP and DMDTP, were detected in the rat both after oral administraion and dermal application with methidathion. And the urinary excretion in dermal application was more delayed than that in oral administration. Based on the results, it tis suggested that three urinary dealkyl phosphates, DMP, DMTP, and DMDTP, could be used as the biomarkers of exposure for methidathion.

Methidation을 흰쥐에 경구투여 및 피부도포 후 뇨 중 대사물질을 GC/MS로 분석하였고, 투여경로에 따른 뇨 중 대사물질의 차이를 비교하였으며, 뇨 중 dialkyl phosphte의 시간별 배설량과 그 외 대사물질을 측정하여 다음과 같은 결과를 얻었다. Methidathion을 경구투여 및 피부도포 후 뇨 중 대사물질을 측정한 결과 유기인계 농약의 공통적인 대사물질인 dialkyl phosphtes 중 세 가지 물질인 DMP, DMTP 및 DMDTP로 동일하게 배설되었다. GC/MS로 주요조각이온을 확인한 결과 DMP는 m/z=153, 127, 109, DMTP는 m/z=198, 142, 109 그리고, DMDTP는 m/z-158, 125, 93에서 분자이온을 확인할 수 있었다. Methidathion을 경구투여 및 피부도포 후 뇨 중 dialkyl phosphtes의 시간별 배설량을 측정한 결과 경구투여의 경우 DMP는 12시간 이내에 79.2%, DMTP는 24시간 이내에 93.3% 그리고, DMDTP는 12시간 이내에 83.0%가 배설되었고, 피부도포의 경우 DMP는 24시간 이내에 71.1%, DMTP와 DMDTP는 48시간 이내에 각각 82.8%, 87.7%가 배설되었다. 이 결과 경구투여 한 실험에서는 48시간 이내에 뇨 중 dialkyl phosphtes가 완전히 배설되는 반면 피부도포 한 실험에서는 각 개체의 상태에 따라 대사물질들이 늦게는 168시간까지 배설이 지연됨을 알 수 있었다. 이상의 결과를 종합하면, 흰쥐에 methidathion을 경구투여 및 피부도포 후 뇨 중 대사물질을 측정한 결과 dialkyl phosphate 중 DMP, DMTP로 검출되었으며, 경구 투여와 피부도포 시 뇨 중 대사물질의 차이는 없었으나, 경구투여보다 피부도포의 경우 배설이 더 지연되었다. 결론적으로, methidathion의 뇨 중 대사물질인 DMP, DMTP 및 DMDTP는 이 농약의 생체모니터링 지표물질로서 사용될 수 있을 것으로 생각된다.

Keywords

References

  1. Richardson, E. R. and Seiber, J. N.: Gas chromatographicdetermination of organophosphorus insecticides and thei dialkyl phosphate metabolites in liver and kidney samples. J.Agr. Food Chem., 41(3), 416-422 (1993) https://doi.org/10.1021/jf00027a014
  2. Fenske, R. A. and Leffingwell, J. T.: Method for thedetermination of dialkyl phosphate metabolites in urine for studies of human exposure to malathion. J. Agric. FoodChem., 37, 995-998 (1989) https://doi.org/10.1021/jf00088a039
  3. Draper, W. M., Wijekoon, D. and Stephens, R. D.:Determination of malathion urinary metabolites by isotopedillution ion tiap GC/MS. J. Agric. Food Chem., 39, 1796-1801 (1991) https://doi.org/10.1021/jf00010a021
  4. Aprea, C., Sciarra, G., Orsi, D., Boccalon, P., Sartorelli, P. andSartorelli, E..: Urinary excretion of alkylphosphates in thegeneral population (Italy). The Science of the TotalEnvironment, 177, 37-41 (1996)
  5. Fest, C. and Schmidt, K.J.: The chemistry of organophosphoruspesticides, Springer- Verlag, Berlin, 337 (1973)
  6. Shafik, T., Bradway, D. E., Enos, H. F. and Yobs, A. R.: Humanexposure to organophosphorus pesticides. A modifiedprocedure for the gas-liquid chromatographic analysis of alkylphosphate metabolites in urine. J. Agr. Food Chem., 21(4),625-629 (1973) https://doi.org/10.1021/jf60188a036
  7. Blair, D. and Rodeiick, H. R.: An improved method for thedetermination of urinary dimethyl phosphate. J. Agr. Food Chem., 24(6), 1221-1223 (1976) https://doi.org/10.1021/jf60208a001
  8. Bradway, D. E. and Shafik, M. T.: Malathion exposure studies. Determination of mono- and dicarboxylic acids and alkylphosphates in urine. J. Agr. Food Chem., 25(6), 1342-1344 (1977) https://doi.org/10.1021/jf60214a002
  9. Lores, E. M. and Bradway, D. E.: Extraction and recovery of organophosphorus metabolites from urine using an anion exchange resin. J. Agr. Food Chem., 25(1), 75-79 (1977) https://doi.org/10.1021/jf60209a040
  10. Churchill , F. C., Ku, D. N. and Miles, J. W.: Gas-liquid chromatographic inlet block derivatization of organophosphorus pesticides and related dialkyl phosphorothioates. J. Agr. FoodChem., 26(5), 1108-1112 (1978) https://doi.org/10.1021/jf60219a015
  11. Takade, D. Y., Reynolds, J. M. and Nelson, J. H.: 1-(4-Nitrobeazy1)-3-(4-to1y1)triazene as a derivatizing reagent for the analysis of urinary dialkyl phosphate metabolites of organophosphorus pesticides by gas chromatography. J. Agr.Food Chem., 27(4), 746-752 (1979) https://doi.org/10.1021/jf60224a003
  12. Daughton, C. G., Cook, A. M. and Alexander, M.: Gas chromatographic determination of phosphorus-containing pesticide metabolites via benzylation. Analyticat Chemistry, 51(12), 1949-1953 (1979) https://doi.org/10.1021/ac50048a014
  13. Bradway, D. E., Moseman, R. and May, R.: Analysis of alkylphosphates by extractive alkylation. Bull. Environm. Contam.Toxicot., 26, 520-523 (1981) https://doi.org/10.1007/BF01622130
  14. Franklin, C. A., Fenske, R. A., Greenhalgh, R., Mathieu, L., Denley, H. V., Leffingwell, J. T, Spear, R. C.: Correlation of urinary pesticide metabolite excretion with estimated dennal contact in the course of occupational exposure to guthion. J. of Toxicology and Environmental Health, 7, 715-731 (1981) https://doi.org/10.1080/15287398109530014
  15. Moody, R. P., Franklin, C. A., Riedel, D., Muir, N. I.,Greenhalgh, R. and Hladka, A.: A new GC on-column methylation procedure for analysis of DMTP(O,O-dimethylphosphorothioate) in urine of workers exposed to fenitrothion. J. Agr. Food Chem., 33(3), 464-467 (1985) https://doi.org/10.1021/jf00063a034
  16. Nutley, B. P. and Cocker, J.: Biological monitoring of workersoccupationally exposed to organophosphorus pesticides.Pestic. Sci., 38, 315-322 (1993) https://doi.org/10.1002/ps.2780380406
  17. Ali, F. A. F. and Fukuto, T. R.: Toxicity of O,O,S-triaIkyl phosphorothioates to the rat. J. Agr. Food Chem., 30(1), 126-130 (1982) https://doi.org/10.1021/jf00109a028
  18. Mahajna, M., Quistad, G. B. and Casida, J. E.: S-Methylationof O,O-dialkyl phosphorodithioic acids: O,O0,S-trimethyl phosphorodithioate and phosphorodithiolate as metabolites of dimethoate in mice. Chem. Res. Toxicol, 9(7), 1202-1206 (1996)
  19. He, F.: Biological monitoring of exposure to pesticides: current issues. Toxicology Letters, 108, 277-283 (1999) https://doi.org/10.1016/S0378-4274(99)00099-5
  20. Moody, R. P. and Nadeau, B.: In vitro dermal absorption of pesticides: IV. In vivo and in vitro comparison with the organophosphorus insecticide diazinon in rat, guinea pig,human and tissue-cultured skin. Toxic. in vitro, 8(6), 1213-1218 (1994) https://doi.org/10.1016/0887-2333(94)90111-2
  21. Sanderson, W. T., Biagini, R., Tolos, W., Henningsen, G. and MacKenzie, B.: Biological monitoring of commercial pesticide applicators for urine metabolites of the herbicide alachlor. Am. Ind. Hyg. Assoc. J., 56, 883-889 (1995) https://doi.org/10.1080/15428119591016511
  22. Fenske, R. A., Schulter, C., Lu, C., Allen, E. H.: Incomplete removal of the pesticide Captan from skin by standard handwash exposure assessment procedures. Bull. Environm. Contam. Toxicol., 61, 194-201 (1998) https://doi.org/10.1007/s001289900748
  23. Griffin, P, Mason, H., Heywood, K. and Cocker, J.: Oral anddermal absorption of chlorpyrifos: a human volunteer study.Occup. Environ. Med., 56, 10-13 (1999) https://doi.org/10.1136/oem.56.1.10
  24. 농약공업협회 : 99'농약년보.농약공업협회(1999)
  25. Tomlin, C.: The pesticide manual. 10th, Crop Protection Publications, U.K., 1994
  26. Marco, G. J., Simoneaux, B. J., Williams, S. C., Cassidy, J. E., Bissig, R. and Muecke, W.: Dennal exposure related topesticide use. ACS, Washington, D. C, 43-61, 1985