Neurotoxicological and statistical analyses of a mixture of five organophosphorus pesticides using a ray design

Toxicological Sciences

Volumn 86, Issue 1, 2005, Pages 101-115

  Moser, V C ^a   Casey, M ^b   Hamm, A ^b   Carter Jr , W H ^b   Simmons, J E ^a   Gennings, C ^b  

^a U S ENVIRONMENTAL PROTECTION AGENCY   (United States)

^b VIRGINIA COMMONWEALTH UNIVERSITY   (United States)

Author keywords

Acephate; Chlorpyrifos; Cumulative risk; Diazinon; Dimethoate; Malathion; Neurotoxicity; Organophosphate mixtures

Indexed keywords

ACEPHATE; CHLORPYRIFOS; CHOLINESTERASE; DIMETHOATE; DIMPYLATE; MALATHION; ORGANOPHOSPHATE PESTICIDE; PESTICIDE;

ANIMAL BEHAVIOR; ANIMAL EXPERIMENT; ANIMAL MODEL; ANIMAL TISSUE; ARTICLE; CONCENTRATION RESPONSE; CONTROLLED STUDY; ENVIRONMENTAL EXPOSURE; ENZYME ACTIVITY; ENZYME BLOOD LEVEL; GAIT; MALE; MOTOR ACTIVITY; NEUROCHEMISTRY; NEUROTOXICITY; NONHUMAN; PREDICTION; RAT; RAT STRAIN; SCORING SYSTEM; STATISTICAL ANALYSIS; TISSUE SECTION; ANIMAL; BLOOD; BRAIN; DOSE RESPONSE; DRUG EFFECT; ENZYMOLOGY; LONG EVANS RAT; METABOLISM;

ANIMALIA;

ANIMALS; BRAIN; CHOLINESTERASES; DOSE-RESPONSE RELATIONSHIP, DRUG; MALE; MOTOR ACTIVITY; PESTICIDES; RATS; RATS, LONG-EVANS;

EID: 26944461642     PISSN: 10966080     EISSN: 10960929     Source Type: Journal    
DOI: 10.1093/toxsci/kfi163     Document Type: Article

References (70)

1. Berenbaum, M. C. (1985). The expected effect of a combination of agents: The general solution. J. Theor. Biol. 114, 413-431.
2. Brunden, M., and Vidmar, T. (1989). Optimal 3 × 3 factorial and 3-ray designs for drug interaction experiments with dichotomous responses. Commun. Statistics 18, 2835-2859.
3. Carpy, S. A., Kobel, W., and Doe, J. (2000). Health risk of low-dose pesticides mixtures: A review of the 1985-1998 literature on combination toxicology and health risk assessment. J. Toxicol. Environ. Health, Part B 3, 1-25.
4. Carter, W. H., Jr. (1995). Relating isobolograms to response surfaces. Toxicology 105, 181-188.
5. Carter, W. H., Jr., Jones, D. E., and Carchman, R. A. (1985). Application of response surface methods for evaluating the interactions of soman, atropine, and pralidioxime chloride. Fundam. Appl. Toxicol. 5, S232-S241.
6. Casey, M., Gennings, C., Carter, W. H., Jr., Moser, V. C., and Simmons, J. E. (2004). Detecting interaction(s) and assessing the impact of component subsets in a chemical mixture using fixed-ratio mixture ray designs. J. Agr. Biol. Environ. Statistics 9, 339-361.
7. s-optimal designs for studying combinations of chemicals using multiple fixed-ratio ray experiments. Environmetrics 16, 129-147.
8. Casey, M., Gennings, C., Carter, W. H., Jr., Moser, V. C., and Simmons, J. E. (in press). Power and sample size calculations for linear hypotheses associated with mixtures of many components using fixed-ratio ray designs. J. Environ. Ecol. Statistics.
9. Casida, J. E., Baron, R. L., Eto, M., and Engel, J. L. (1963). Potentiation and neurotoxicity induced by certain organophosphates. Biochem. Pharmacol. 12, 73-78.
10. Chambers, J. E., and Carr, R. L. (1993). Inhibition patterns of brain acetylcholinesterase and hepatic and plasma aliesterases following exposures to three phosphorothionate insecticides and their oxons in rats. Fund. Appl. Toxicol. 21, 111-119.
11. Chambers, J. E., Ma, T., Boone, J. S., and Chambers, H. W. (1994). Role of detoxication pathways in acute toxicity levels of phosphorothionate insecticides in the rat. Life Sci. 54, 1357-1364.
12. Chanda, S. M., Mortensen, S. R., Moser, V. C., and Padilla, S. (1997). Tissue-specific effects of chlorpyrifos on carboxylesterase and cholinesterase activity in adult rats: An in vitro and in vivo comparison. Fundam. Appl. Toxicol. 38, 148-157.
13. Chaudhuri, J., Chakraborti, T. K., Chanda, S., and Pope, C. N. (1993). Differential modulation of organophosphate-sensitive muscarinic receptors in rat brain by parathion and chlorpyrifos. J. Biochem. Toxicol. 8, 207-216.
14. Chen, J. J., Che, Y.-J., Rice, G., Teuschler, L. K., Hamernik, K., Protzel, A., and Kodell, R. L. (2001). Using dose addition to estimate cumulative risks from exposure to multiple chemicals. Reg. Toxicol. Pharmacol. 34, 35-41.
15. Clement, J. G. (1984). Role of aliesterase in organophosphate poisoning. Fundam. Appl. Toxicol. 4, S96-S105.
16. Cohen, S. D. (1984). Mechanisms of toxicological interactions involving organophosphate insecticides. Fundam. Appl. Toxicol. 4, 315-324.
17. Cohen, S. D., and Murphy, S. D. (1971a). Carboxylesterase inhibition as an indicator of malathion potentiation in mice. J. Pharmacol. Exp. Ther 176, 733-742.
18. Cohen, S. D., and Murphy, S. D. (1971b). Malathion potentiation and inhibition of hydrolysis of various carboxylic esters by triorthotolyl phosphate (TOTP) in mice. Biochem. Pharmacol. 20, 575-587.
19. Cohen, S. D., and Murphy, S. D. (1974). A simplified bioassay for organophosphate detoxification and interactions. Toxicol. Appl. Pharmacol. 27, 537-550.
20. DuBois, K. P. (1961). Potentiation of the toxicity of organophosphorus compounds. Adv. Pest Control Res. 4, 117-151.
21. DuBois, K. P. (1969). Combined effects of pesticides. Can. Med. Assoc. J. 100, 173-179.
22. Ecobichon, D. J. (1996). Toxic effects of pesticides. In Casarett and Doull's Toxicology (C. D. Klaassen, M. O. Amdur, and J. Doull, Eds.), pp. 643-689. McGraw-Hill, New York.
23. El-Masri, H. A., Mumtaz, M. M., and Yushak, M. L. (2004). Application of physiologically-based pharmacokinetic modeling to investigate the toxicological interaction between chlorpyrifos and parathion in the rat. Environ. Toxicol. Pharmacol. 16, 57-71.
24. Finney, D. J. (1964). Probit Analysis. Cambridge University Press, London.
25. Fleisher, J. H., Harris, L. W., Prudhomme, C., and Bursel, J. (1963). Effects of ethyl p-nitrophenyl thionobenzene phosphonate (EPN) on the toxicity of isopropyl methyl phosphonofluoridate (GB). J. Pharmacol. Exp. Ther. 139, 390-396.
26. Frawley, J. P., Fuyat, H. N., Hagan E. C., Blake, J. R., and Fitzhugh, O. G. (1957). Marked potentiation in mammalian toxicity from simultaneous administration of two anticholinesterase compounds. J. Pharmacol. Exp. Ther. 121, 96-106.
27. Gennings, C. (1995). An efficient experimental design for detecting departure from additivity in mixtures of many chemicals. Toxicology 105, 189-197.
28. Gennings, C., and Carter, W. H., Jr. (1995). Utilizing concentration-response data from individual components to detect statistically significant departures from additivity in chemical mixtures. Biometrics 51, 1264-1277.
29. Gennings, C., Carter, W. H., Jr., Campain, J. A., Bae, D., and Yang, R. S. H. (2002). Statistical analysis of interactive cytotoxicity in human epidermal keratinocytes following exposure to a mixture of four metals. J. Agric. Biol. Environ. Stat. 7, 58-73.
30. Gennings, C., Carter, W. H., Jr., Casey, M., Moser, V., Carchman, R., and Simmons, J. E. (2004). Analysis of functional effects of a mixture of five pesticides using a ray design. Environ. Toxicol. Pharmacol. 18, 115-125.
31. Gennings, C., Schwartz, P., Carter, W. H., Jr., and Simmons, J. E. (1997). Detection of departures from additivity in mixtures of many chemicals with a threshold model. J. Agric. Biol. Environ. Stat. 2, 198-211.
32. Gessner, P. K. (1974). The isobolographic method applied to drug interactions. In Drug Interactions (P. L. Morselli, S. Garattini, and S. N. Cohen, Eds.), pp. 349-362. Raven Press, New York.
33. Hussain, M. A., Mohamad, R. B., and Oloffs, P. C. (1985). Studies on the toxicity, metabolism, and anticholinesterase properties of acephate and methamidophos. J. Environ. Sci. Health B20, 129-147.
34. Johnson, C. D., and Russell, R. L. (1975). A rapid, simple radiometric assay for cholinesterase, suitable for multiple determinations. Anal. Biochem. 64, 229-238.
35. Karanth, S., Liu, J., Olivier, K., Jr., and Pope, C. (2004). Interactive toxicity of the organophosphorus insecticides chlorpyrifos and methyl parathion in adult rats. Toxicol. Appl. Pharmacol. 196, 183-190.
36. Karanth, S., Olivier, K., Jr., Liu, J., and Pope, C. (2001). In vivo interaction between chlorpyrifos and parathion in adult rats: Sequence of administration can markedly influence toxic outcome. Toxicol. Appl. Pharmacol. 177, 247-255.
37. Kardos, S. A., and Sultatos, L. G. (2000). Interactions of the organophosphates paraoxon and methyl paraoxon with mouse brain acetylcholinesterase. Toxicol. Sci. 58, 118-126.
38. Kousba, A. A., Sultatos, L. G., Poet, T. S., and Timchalk, C. (2004). Comparison of chlorpyrifos-oxon and paraoxon acetylcholinesterase inhibition dynamics: Potential role of a peripheral binding site. Toxicol. Sci. 80, 239-248.
39. Lauwerys, R. R., and Murphy, S. D. (1969). Interaction between paraoxon and tri-o-tolyl phosphate in rats. Toxicol. Appl. Pharmacol. 14, 348-357.
40. Maxwell, D. M. (1992). Detoxication of organophosphorus compounds by carboxylesterase. In Organophosphates: Chemistry, Fate, and Effects (J. E. Chambers, and P. E. Levi, Eds.), pp. 183-199. Academic Press, New York.
41. McCullagh, P., and Nelder, J. A. (1989). Generalized Linear Models, 2nd ed. Chapman and Hall, New York.
42. Moser, V. C. (1995). Comparisons of the acute effects of cholinesterase inhibitors using a neurobehavioral screening battery in rats. Neurotoxicol. Teratol. 17, 617-625.
43. Moser, V. C., and Padilla, S. (1998). Age- and gender-related differences in the time course of behavioral and biochemical effects produced by oral chlorpyrifos in rats. Toxicol. Appl. Pharmacol. 149, 107-119.
44. Murphy, S. D., Anderson, R. L., and DuBois, K. P. (1959). Potentiation of toxicity of malathion by triorthotolyl phosphate. Proc. Soc. Exp. Biol. Med. 100, 387-483.
45. Murphy, S. D., Cheever, K. L., Chow, A. Y. K., and Brewster, M. (1976). Organophosphate insecticide potentiation by carboxylesterase inhibitors. Proc. Eur. Soc. Tax. XVII Esc. Med. Int. Cong. 376, 292-300.
46. Murphy, S. D., and DuBois, K. P. (1957). Quantitative measurement of inhibition of the enzymatic detoxification of malathion by EPN (ethyl p-nitrophenyl thionobenzene phosphate). Proc. Soc. Exp. Biol. Med. 96, 813-818.
47. Naguib, M., Farsci, F., and Yaksh, T. L. (1997). Characterization of muscarinic receptor subtypes that mediate antinociception in the rat spinal cord. Anesth. Analg. 85, 847-853.
48. National Research Council. (1989). Acetylcholinesterase inhibitors: Case study of mixtures of contaminants with similar biological effects. In Drinking Water and Health. Selected Issues in Risk Assessment. Part II. Mixtures. Vol. 9, pp. 146-161. National Academy Press, Washington, DC.
49. Nostrandt, A. C., Padilla, S., and Moser, V. C. (1997). The relationship of oral chlorpyrifos effects on behavior, cholinesterase inhibition, and muscarinic receptor density in rat. Pharmacol. Biochem. Behav. 58, 15-23.
50. Pedigo, N. W., Dewey, W. L., and Harris, L. S. (1975). Determination and characterization of the antinociceptive activity of intraventricularly administered acetylcholine in mice. J. Pharmacol. Exp. Ther. 193, 845-852.
51. Poet, T. S., Kousba, A. A., Dennison, S. L., and Timchalk, C. (2004). Physiologically based pharmacokinetic/pharmacodynamic model for the organophosphorus pesticide diazinon. Neurotoxicol. 25, 1013-1030.
52. Pond, A. L., Chambers, H. W., and Chambers, J. E. (1995). Organophosphate detoxication potential of various rat tissues via A-esterase and aliesterase activities. Toxicol. Letters 78, 245-252.
53. Pope, C. N. (1999). Organophosphorus pesticides: Do they all have the same mechanism of toxicity? J. Toxicol. Environ. Health, Part B, 2, 161-181.
54. Reiter, L. W. (1983). Chemical exposures and animal activity: Utility of the figure-eight maze. Dev. Toxicol. Environ. Sci. 11, 73-84.
55. Safe, S. H. (1998). Hazard and risk assessment of chemical mixtures using the toxic equivalency factor approach. Environ. Health Perspect. 106(Suppl. 4), 1051-1058.
56. Seume, F. W., Casida, J. E., and O'Brien, R. D. (1960). Effects of parathion and malathion separately and jointly upon rat esterases in vivo. Agricul. Food Chem. 8, 43-47.
57. Solana, R. P., Gennings, C., Carter, W. H., Jr., Anderson, D., Lennox, W. J., Carchman, R. A., and Harris, L. W. (1990a). Evaluation of the efficacy of two carbamates, physostigmine and pyridostigmine, when used in conjunction for protection against organophosphate exposure. Fundam. Appl. Toxicol. 15, 814-819.
58. Solana, R. P., Harris, L. W., Carter, W. H., Jr., Talbot, B. G., Carchman, R. A., and Gennings, C. (1990b). Evaluation of a two-drug combination pretreatment against organophosphorus exposure. Toxicol. Appl. Pharmacol. 102, 421-429.
59. Su, M.-Q., Kinoshita, F. K., Frawley, J. P., and DuBois, K. P. (1971). Comparative inhibition of aliesterases and cholinesterase in rats fed eighteen organophosphorus insecticides. Toxicol. Appl. Pharmacol. 20, 241-249.
60. Teuschler, L., Klaunig, J., Carney, E., Chambers, J., Connolly, R., Gennings, C., Giesy, J., Hertzberg, R., Klaassen, C., Kodell, R., Paustenbach, D., and Yang, R. (2002). Support of science-based decisions concerning the evaluation of the toxicology of mixtures: A new beginning. Reg. Toxicol. 36, 34-39.
61. Timchalk, C., Nolan, R. J., Mendrala, A. L., Dittenber, D. A., Brzak, K. A., and Mattsson, J. L. (2002). A physiologically based pharmacokinetic and pharmacodynamic (PBPK/PD) model for the organophosphate insecticide chlorpyrifos in rats and humans. Toxicol. Sci. 66, 34-53.
62. Timchalk, C., Poet, T. S., Hinman, M. N., Busby, A. L., and Kousba, A. A. (in press). Pharmacokinetic and pharmacodynamic interaction for a binary mixture of chlorpyrifos and diazinon in the rat. Toxicol. Appl. Pharmacol.
63. Uchiyama, M., Yoshida, T., Homma, K., and Hongo, T. (1975). Inhibition of hepatic drug-metabolizing enzymes by thiophosphate insecticides and its drug toxicological implications. Biochem. Pharmacol. 24, 1221-1225.
64. U.S. Department of Agriculture. (2000). Pesticide Data Program: Annual Summary Calendar Year 1998, http://www.ams.usda.gov/science/pdp/.
65. U.S. Environmental Protection Agency. (1999). Pesticide Industry Sales and Usage, 1996 and 1997 Market Estimates, http://www.epa.gov/oppbead1/ pestsales/.
66. U.S. Environmental Protection Agency. (2001). Organophosphate Pesticides: Preliminary OP Cumulative Risk Assessment, http://www.epa.gov/oppsrrd1/cumulative/pra-op/newdesign.htm.
67. U.S. Environmental Protection Agency. (2002). Organophosphate Pesticides: Revised OP Cumulative Risk Assessment, http://www.epa.gov/pesticides/cumulative/rra-op/.
68. U.S. Food and Drug Administration. (2000). Pesticide Program: Residue Monitoring, 1999, http://www.cfsan.fda.gov/~download/pes99db.html.
69. Ward, T. R., and Mundy, W. R. (1996). Organophosphorus compounds preferentially affect second messenger systems coupled to M2/M4 receptors in rat frontal cortex. Brain Res. Bull. 39, 49-55.
70. Wu, H. X., Evreux-Gros, C., and Descotes, J. (1996). Diazinon toxicokinetics, tissue distribution and anticholinesterase activity in the rat. Biomed. Environ. Sci. 9, 359-369.