IJCRR - 8(4), February, 2016
TISSUE DISTRIBUTION AND PHARMACOKINETICS OF BROMOXYNIL IN RAT
Author: Ahmed K. Salama, Khaled A. Osman, Ahmed S. El-Bakary, Maher S. Salama
The tissue distribution and excretion of bromoxynil were studied in male rat. A single oral dose of 12.9 mg bromoxynil /kg body weight was administered to rat. Rats were killed after 0.5, 1, 3, 6, 12, 24, 48, 72, 120, and 168 h. At termination of 24 h, 2.80 and 0.01 % of the compound were excreted in the urine and feces, respectively. By 168 h the urinary and fecal cumulative excretion rose to 21.90 and 14.11%, respectively. Bromoxynil was readily absorbed and subsequently distributed throughout the body. Bromoxynil concentrations increased in serum as the time passed reaching a peak concentration of 256.09ng/ml at 48 h following administration. Peak concentrations of bromoxynil were also reached at 48 h in liver (345.15ng/g) and brain (67.85ng/g). However, bromoxynil level in kidneys reached peak concentration (647.19ng/g) at 24 h after dosing. Bromoxynil begin to decline in the tissues as time passed to reach 10.67, 27.86 and 22.31ng/g(ml) in serum, liver and kidneys, respectively. In case of brain, the lowest amount of bromoxynil (23.01ng/g) reached at 120 h and disappeared after 168 h following administration. Bromoxynilwas disappeared biexponentially from serum, liver, kidneys and brain. The terminal half-life t½ of bromoxynil was 48.0, 62.0, 60.0, and 34.8 h for the serum, liver, brain and kidneys, respectively. This indicates that there was no tendency for bromoxynil to retain in rat tissue.
Keywords: Bromoxynil, Pharmacokinetics, Distribution, Excretion, Rat
Ahmed K. Salama, Khaled A. Osman, Ahmed S. El-Bakary, Maher S. Salama. TISSUE DISTRIBUTION AND PHARMACOKINETICS OF BROMOXYNIL IN RAT International Journal of Current Research and Review. 8(4), February, 54-60
1. Agriculture Canada (1989): CAPCO (Canadian Association of Pesticide Control Officials) note on bromoxynil.Ottawa, Ontario: Pesticides Directorate, Agriculture Canada.
2. Bakry, N.M., Abdel-Halim, K.Y. and Salama, A.K. Placental and milk transfer of chlorpyrifos and profenofos in mice. Alex. J. Pharm. Sci. 1999; (13): 29 – 33
3. Bogus, E.R., Watschke, T.L. and Mumma, R.O. Utilization of solid-phase extraction and reversed-phase and ion-pair chromatography in the analysis of seven agrochemicals in water. J. Agric. Food Chem. 1990; 38: 142-144
4. Caldwell, J., Gardner, I., and Swales, N.An introduction to drug disposition: the basic principles of absorption, distribution, metabolism, and excretion. ToxicolPathol. 1995; 23, 102-14.
5. Cessna, A.J. and Grover, R. Exposure of Ground-Rig Applicators to the Herbicide Bromoxynil Applied as a 1:1 Mixture of Butyrate and Octanoate. Archives of Environmental Contamination and Toxicology. 2002; 42(3): 369-382.
6. Deziel, N., Friesen, M., Hoppin, J. Hines, C. Thomas, K. and Freeman, L. (2015). A Review of Nonoccupational Pathways for Pesticide Exposure in Women Living in Agricultural Areas. Environ Health Perspect. 123(6): 515–524.
7. EPA (1974): Manual of analytical quality control for pesticides in human and environmental media. Research Triangle Park, N.C. 27711, USA
8. EPA (1979): Manual of analytical quality control for pesticides in human and environmental media. Research Triangle Park, N.C. 27711, USA
9. Gillette, J.R. The importance of tissue distribution in pharmacokinetics. In: Pharmacology and pharmacokinetics, ed. Toerell, T; Dedrick, R.L.; Canliffe, P.G. 1974;(pp. 209-231) Plenum Press, New York.
10. Inter-Organization Programme for the Sound Management of Chemicals (IOMC) (2004): International Programme on Chemical Safety: The WHO recommended classification of pesticides by hazard and guidelines to classification 2000–2002.
11. Lovecka, P., Thimova, M. Grznarova, P., Lipov, J., Knejzlik, Z., Stiborova, H., Nindhia, T., Demnerova, K., Ruml, T. (2015). Study of Cytotoxic Effects of Benzonitrile Pesticides. Biomed Res Int. 2015: 381264.
12. Salama, A.K. Pharmacokinetic and metabolism of methamidophos in female mice following a single oral administration. Alex. J. Agric. Res. 1992; 37(1): 431-445.
13. Salama, A.K., Bakry, N.M., Aly, H.A. and Abou-Donia, M.B.Placental and milk transfer, disposition, and elimination of a single oral dose of [14C-acetyl] acephate in Sprague-Dawley rats. J. Occupational Medicine and Toxicology. 1992a; 1(3): 265- 274.
14. Salama, A.K., Bakry, N.M., Aly, H.A. and Abou-Donia, M.B. (1992b).Placental and milk transfer, disposition, and metabolism of a single oral dose of [14CH3 S] methamidophos in SpragueDawley rats. J. Occupational Medicine and Toxicology. 1992c; 1(3): 275-291.
15. Salama, A.K., Radwan, M.A. and Bakry, N.M.Pharmacokinetics and excretion of ametryn in rat following a single oral administration. J. Pest Cont. Environ. Sci. 1993; 5(1): 61-76
16. Salama, A.K., Radwan, M.A. and El-Shahawi, F. Pharmacokinetic profile and anticholinesterase properties of phenamiphos in male rats. J. Environ. Sci. and Health B. 1992; 27(3): 307-323
17. Stahler, M., Gericke, S. and Beitz, H. Results of the toxicokinetics of bromoxynil in rats. Zeitschriftfur die Gesamte Hygiene und Ihre Grenzgebiete. 1991;37(2): 56-58.
18. Tomlin, C. D. S., ed. (1997): The pesticide manual: A world compendium, 11th ed. Farnham, Surrey, United Kingdom: British Crop Protection Council.
19. U.S. Environmental Protection Agency (1997): Bromoxynil; Pesticide tolerances. Fed. Reg. 62(85):24065–24073. Available from http://www.epa.gov/fedrgstr/EPA-PEST/1997/May/Day02/p11504.htm.
20. U.S. Environmental Protection Agency (1998). Registration Eligibility Decision (RED) Bromoxynil. Washington, DC, USA: United States Environmental Protection Agency.
21. U.S. Environmental Protection Agency (2005): Bromoxynil. EPA738-R-98-013 December 1998. Available from, as of Feb. 1, 2005:http://www.epa.gov/pesticides/reregistration/status.htm
22. Xie, Y., Zhong, G., He, H., Fan, G. and Wu, Y. Pharmacokinetics, tissue distribution and excretion of porcine fibrinogen after intraperitoneal injection of a porcine-derived fibrin glue to rats. J Pharm Biomed Anal.2011; 54: 148-53.