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Archives of Toxicology

, Volume 66, Issue 3, pp 170–174 | Cite as

Oral and dermal application of 2,4-dichlorophenoxyacetic acid sodium and dimethylamine salts to male rats: Investigations on absorption and excretion as well as induction of hepatic mixed-function oxidase activities

  • Dietmar Knopp
  • Frank Schiller
Original Investigations

Abstract

Absorption and urinary excretion of 2,4-dichlorophenoxyacetic acid sodium (sodium 2,4-D) and 2,4-dichlorophenoxyacetic acid dimethylammonium (2,4-DMA) salts were examined after single oral and middorsal skin applications of the herbicides to male rats. Doses of 2.6 mg 2,4-D/kg body wt (sodium 2,4-D) and 1.9 mg 2,4-D/kg body wt (2,4-DMA) were applied. Quantitatively, with both salts, most of the orally administered herbicide (over 90%) was excreted in urine within 28 h. However, 2,4-D urinary peak concentrations were measured 4.5 and 20.5 h after dosing with 2,4-DMA and sodium 2,4-D, respectively. Additionally, the volume of urine in the oral study was significantly increased with both salts when compared with the controls or the dermal exposure. After topical application, 2,4-D absorption was much lower than in the oral study. Urinary excretion only reached about 10 and 15% of the applied dose for sodium 2,4-D and 2,4-DMA, respectively, by 5 days post-treatment. Further, we found some elevations in hepatic cytochrome P-450 activities. Ethylmorphine N-demethylase was only slightly induced by the herbicides while ethoxyresorufin O-deethylase activity was increased nearly 2-fold by sodium 2,4-D.

Key words

2,4-D Spritz Hormit (sodium 2,4-D) Spritz Hormin (2,4-DMA) Rats Urinary excretion Cytochrome P-450 

Abbreviations

2,4-D

2,4-dichlorophenoxyacetic acid

sodium 2,4-D

2,4-dichlorophenoxyacetic acid sodium salt

2,4-DMA

2,4-dichlorophenoxyacetic acid dimethylammonium salt

2,4,5-T

2,4,5-trichlorophenoxyacetic acid

MCPA

4-chloro-2-methylphenoxyacetic acid

2,4-DP

2-(2,4-dichlorophenoxy) propionic acid

EN

ethylmorphin N-demethylase

EROD

ethoxyresorufin O-deethylase

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References

  1. Bacher MA, Gibson GG (1988) Chlorophenoxyacid herbicides induce microsomal cytochrome P-450 IVA1 (P-452) in rat liver. Chem Biol Interact 65: 145–156PubMedGoogle Scholar
  2. Bräunlich H, Bernhardt H, Bernhardt I (1989) Renal handling of 2-methyl-4-chlorophenoxyacetic acid (MCPA) in rats. J Appl Toxicol 9: 255–258PubMedGoogle Scholar
  3. Chemie AG Wolfen/Bitterfeld (1990) Certificate of 2,4-D analysis Ciba-Geigy, Basel, 1980Google Scholar
  4. Feldmann RJ, Maibach HI (1974) Percutaneous penetration of some pesticides and herbicides in man. Toxicol Pharmacol 28: 126–132Google Scholar
  5. Hietanen E, Linnainmaa K, Vainio H (1983) Effects of phenoxyherbicides and glyphosate on the hepatic and intestinal biotransformation activities in the rat. Acta Pharmacol Toxicol 53: 103–112Google Scholar
  6. Khanna S, Fang SC (1966) Metabolism of14C-labeled 2,4- dichlorophenoxyacetic acid in rats. J Agric Food Chem 14: 500–503Google Scholar
  7. Klinger W, Müller D (1977) Ethylmorphin-N-demethylation by liver homogenate of newborn and adult rats. Acta Biol Med Germ 36: 1149–1159PubMedGoogle Scholar
  8. Knopp D, Glass S (1991) Biological monitoring of 2,4-dichlorophenoxyacetic acid exposed workers in agriculture and forestry. Int Arch Occup Environ Health (in press)Google Scholar
  9. Knopp D, Nuhn P, Dobberkau HJ (1985) Radioimmunoassay for 2,4(−)dichlorophenoxyacetic acid. Arch Toxicol 58: 27–32PubMedGoogle Scholar
  10. Knopp D, Richter G, Skerswetat M, Hermenau H, Stottmeister E (1991) Assessment of 2,4-dichlorophenoxyacetic acid exposure in chemical industry through biological monitoring. Advances in Controlled Clinical Inhalation Studies, 3rd Inhalation Symposium, 9–11 October 1991, Hannover, FRGGoogle Scholar
  11. Lilienfeld DE, Gallo MA (1989) 2,4-D, 2,4,5-T, and 2,3,7,8-TCDD: an overview. Epidemiol Rev 11: 28–58PubMedGoogle Scholar
  12. Lukowicz-Ratajczak J, Krechniak J (1988) Effects of sodium 2,4(−)dichlorophenoxyacetate on renal function in the rat. Bull Environ Contam Toxicol 41: 815–821PubMedGoogle Scholar
  13. Moody RP, Franklin CA, Ritter L, Maibach HI (1990) Dermal absorption of the phenoxy herbicides 2,4-D, 2,4-D amine, 2,4-D isooctyl, and 2,4,5-T in rabbits, rats, rhesus monkeys, and humans: a cross-species comparison. J Toxicol Environ Health 29: 237–245PubMedGoogle Scholar
  14. Mustonen R, Elovaara E, Zitting A, Linnainmaa K, Vainio H (1989) Effects of commercial chlorophenolate, 2,3,7,8-TCDD, and pure phenoxyacetic acids on hepatic peroxisome proliferation, xenobiotic metabolism and sister chromatid exchange in the rat. Arch Toxicol 63: 203–208PubMedGoogle Scholar
  15. Pelletier O, Ritter L, Caron J, Somers D (1989) Disposition of 2,4- dichlorophenoxyacetic acid dimethylamine salt by fisher 344 rats dosed orally and dermally. J Toxicol Environ Health 28: 221–234PubMedGoogle Scholar
  16. Pohl RJ, Fouts JR (1980) A rapid method for assaying the metabolism of 7-ethoxyresorufin by microsomal subcellular reactions. Anal Biochem 107: 150–155PubMedGoogle Scholar
  17. Shah PV, Fisher HL, Sumler MR, Monroe RJ, Chernoff N, Hall LL (1987) Comparison of the penetration of 14 pesticides through the skin of young and adult rats. J Toxicol Environ Health 21: 353–366PubMedGoogle Scholar
  18. Wingren G, Fredrikson M, Noorlind Brage H, Nordenskjöld B, Axelson O (1990) Soft tissue sarcoma and occupational exposures. Cancer 66: 806–811PubMedGoogle Scholar

Copyright information

© Springer-Verlag 1992

Authors and Affiliations

  • Dietmar Knopp
    • 1
  • Frank Schiller
    • 1
  1. 1.Research Department Bad ElsterInstitute for Water, Soil and Air Hygiene of the Federal Health OfficeBad ElsterFederal Republic of Germany

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