Pathology has been a cornerstone of toxicity testing for many years and is an integral part of the primary tier screen in the testing of drugs and chemicals for neurotoxicity. Because of the special nature of nervous tissue and its anatomical complexity, the approach to the evaluation can influence in a major way the effectiveness of the task. This report discusses issues which may account for variation in the degree of neuropathological assessment between laboratories. Both systematic and flexible approaches to the evaluation of neuropathology are discussed.
References
1.
1. O'Donoghue, J.L. (1989). Screening for neurotoxicity using a neurologically based examination and neuropathology. J. Am. Coll. Toxicol.8, 97–115.
2.
2. Broxup, B., Losos, G., and Yipchuck, G. (1989). Quantitation in neuropathology. J. Am. Coll. Toxicol.8, 225–232.
3.
3. U.S. Environmental Protection Agency Office of Toxic Substances. (1985). Toxic Substances Control Act Test Guidelines: Final Rule. 40 CFR Par 798: Health Effects Testing Guidelines. Subpart G—Neurotoxicity. Fed. Reg.50, 39, 458–470.
4.
4. WHO (1986). Principles and Methods for the Assessment of Neurotoxicity Associated with Exposure to Chemicals, Environmental Health Criteria Series 60. Geneva: World Health Organization.
5.
5. Clark, A.W., Griffin, J.W., and Price, D.L. (1980). The axonal pathology in chronic IDPN intoxication. J. Neuropathol. Exp. Neurol.39, 42–55.
6.
6. Spencer, P.S. and Schaumberg, H.H. (1974). A review of acrylamide neurotoxicity. Part II, Experimental animal neurotoxicity and pathologic mechanisms. Can. J. Neurol. Sci.1, 152–189.
7.
7. Eisenbrandt, D.L., Mattsson, J.L., Albee, R.R., Spencer, P.J., and Johnson, K.A. (1990). Spontaneous lesions in subchronic neurotoxicity testing of rats. Toxicol. Pathol.18, 154–164.
8.
8. Weibel, E.R. (1979). Stereological Methods. New York: Academic Press.
9.
9. Griffen, J.W. (1990). Basic pathologic processes in the nervous system. Toxicol. Pathol.18, 83–88.
10.
9. Zeman, W. and Innes, J.R.M. (1963). Craigie's Neuroanatomy of the Rat. New York: Academic Press.
11. Spencer, P.S. and Bischoff, M.C. (1982). Contemporary neuropathological methods in toxicology. In: Mitchell, C.L., ed. Nervous System Toxicology. New York: Raven Press.
13.
12. U.S. Congress, Office of Technology Assessment. (1990). Neurotoxicity: Identifying and Controlling Poisons of the Nervous System, OTA-Ba-436, Washington, D.C.
14.
13. Krinke, G.J. (1989). Neuropathologic screening in rodent and other species. J. Am. Coll. Toxicol.8, 141–146.
15.
14. Spencer, P.S. (1990). Structural and functional basis for neurotoxicology. In: Bolans, G.N., Sims, J.S., Sullivan, F.M., and Turner, P., eds. Basic Science in Toxicology. London: Taylor & Francis.
16.
15. Gad, S.C. (1989). Principles of screening in toxicology with special emphasis on applications to neurotoxicology. J. Am. Coll. Toxicol.8, 21–27.
17.
16. Broxup, B., Robinson, K., Losos, G., and Beyrouty, P. (1989). Correlation between behavioral and pathological changes in the evaluation of neurotoxicity. Toxicol. Appl. Pharmacol.101, 510–520.
18.
17. Norton, S. (1982). Behavior versus morphology as an indicator of central nervous system toxicity. Nerv. Sys. Toxicol. 247–258.
19.
18. Mattsson, J.L., Eisenbrandt, D.L., and Albee, R.R. (1990). Screening for neurotoxicity: Complementarity of functional and morphologic techniques. Toxicol. Pathol.18, 115–127.
20.
19. Paxinos, G. and Watson, C. (1982). The Rat Brain in Stereotaxic Coordinates, First Edition. New York: Academic Press.
21.
20. Brierley, J.B. and Graham, D.I. (1984). Hypoxia and vascular disorders of the central nervous system. In: Hume Adams, J., Corsellis, J.A.N. and Duchen, L.W., eds. Greenfield's NeuropathologyLondon: Edward Arnold.
22.
21. Martins, A.N., Johnston, J.S., Henry, J.M., Stoffel, T.J., and Dichiro, G. (1977). Delayed radiation necrosis of the brain. J. Neurosurg.47, 336–345.
23.
22. Burns, R.S., Markey, S.P., Phillips, J.M., and Chiveh, C.C. (1984). The neurotoxicity of l-methyl-4-phenyl-1,2,3,6-tetrahydropyridine in the monkey and man. Can. J. Neurotoxicol. Sci.11, 166–168.
