Risk Assessment and Neurotoxicology

William Slikker1

1 National Center for Toxicological Research, Food and Drug Administration, Jefferson, Arkansas
Publication Name:  Current Protocols in Toxicology
Unit Number:  Unit 11.6
DOI:  10.1002/0471140856.tx1106s02
Online Posting Date:  May, 2001
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Risk assessment refers to the use of toxicological data to define the relationship between the exposure to an agent and an adverse health outcome. This unit describes the factors involved in the study and evaluation of neurotoxicants to assess the risks associated with exposure.

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Table of Contents

  • Aims and Objectives
  • Risk Assessment
  • Biological Markers
  • Assessing Human Neurotoxicity
  • Animal Models
  • Traditional Risk Assessment Procedures for Neurotoxicants
  • Limitations and Assumptions
  • Quantitative Dose‐Response‐Based Risk Assessment Approaches
  • Biologically Based Risk Assessment
  • Conclusion
  • Literature Cited
  • Tables
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Literature Cited

Literature Cited
   Abdel‐Rahman, M.S. and Kadry, A.M. 1995. Studies on the use of uncertainty factors in deriving RFDs. Hum. Ecol. Risk Assess. 1:614‐624.
   Barnes, D.G. and Dourson, M. 1988. Reference dose (RfD): Description and use in health risk assessments. Regul. Toxicol. Pharmacol. 8:471‐486.
   Chang, L.W. and Slikker, W. Jr. 1995. Neurotoxicology: Approaches and Methods. Academic Press, San Diego.
   Crump, K.S. 1984. A new method for determining allowable daily intakes. Fundam. Appl. Toxicol. 4:854‐871.
   Dews, P.B. 1986. On the assessment of risk. In Developmental Behavioral Pharmacology (N. Krasnegor, J. Gray, and T. Thompson, eds.) pp. 53‐65. Lawrence Erlbaum Associates, Hillsdale, N.J.
   Environmental Protection Agency (EPA). 1998. Guidelines for Neurotoxicity Risk Assessment. Fed. Regist. 63:26925‐26954.
   Gaylor, D.W. and Slikker, W. Jr. 1990. Risk assessment for neurotoxic effects. Neurotoxicology 11:211‐218.
   Gaylor, D.W. and Slikker, W. Jr. 1992. Risk assessment for neurotoxicants. In Neurotoxicology. (H. Tilson and C. Mitchell, eds.) pp. 331‐343. Raven Press, New York.
   Gaylor, D.W., Axelrad, J.A., Brown, R.P., Cavagnaro, J.A., Cyr, W.H., Hulebak, K.L., Lorentzen, R.J., Miller, M.A., Mulligan, L.T., and Schwetz, B.A. 1997. Health risk assessment practices in the U.S. Food and Drug Administration. Regul. Toxicol. Pharmacol. 26:307‐321.
   Glowa, J.R., DeWesse, J., Natale, M.E., and Holland, J.J. 1983. Behavioral toxicology of volatile organic solvents. I. Methods: Acute effects. J. Am. Coll. Toxicol. 2:175‐185.
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   Kadry, A.M., Skowronski, G.A., and Abdel‐Rahman, M.S. 1995. Evaluation of the use of uncertainty factors in deriving RfDs for some chlorinated compounds. J. Toxicol. Environ. Health 45:83‐95.
   Kim, C.S., Slikker, W. Jr., Binienda, A., Gargas, M.L., and Andersen, M.E. 1995. Development of a physiologically based pharmacokinetic model for 2,4‐dichlorophenoxyacetic acid dosimetry in discrete areas of the rabbit brain. Neurotoxicol. Teratol. 17:111‐120.
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   Reiter, L.W., Tilson, H.A., Dougherty, J., Harry, G.J., Jones, C.J., McMaster, S., Slikker, W. Jr., and Sobotka, T.J. 1994. Final Report: Principles of neurotoxicity risk assessment. Fed. Regist. 59(158):42360‐42404.
   Slikker, W. Jr. 1991. Biomarkers of neurotoxicity: An overview. Recent advances on biomarker research. Biomed. Environ. Sci. 4:192‐196.
   Slikker, W. Jr. 1994a. Placental transfer and pharmacokinetics of developmental neurotoxicants. In Principles of Neurotoxicology (L. Chang, ed.) pp. 659‐680. Marcel Dekker, New York.
   Slikker, W. Jr. 1994b. Principles of developmental neurotoxicology. Neurotoxicology 15:11‐16.
   Slikker, W. Jr. and Chang, L.W. 1998. Handbook of Developmental Neurotoxicology. Academic Press, San Diego.
   Slikker, W. Jr. and Gaylor, D.W. 1990. Biologically based dose‐response model for neurotoxicity risk assessment. Korean J. Toxicol. 6:204‐213.
   Slikker, W. Jr. and Gaylor, D.W. 1995a. Concepts on quantitative risk assessment of neurotoxicants. In Neurotoxicology: Approaches and Methods (L.W. Chang and W. Slikker Jr., eds.) pp. 771‐776. Academic Press, San Diego.
   Slikker, W. Jr. and Gaylor, D.W. 1995b. Risk assessment strategies for neuroprotective agents. Ann. N.Y. Acad. Sci. 765:198‐208.
   Slikker, W. Jr. and Sobotka, T.J. 1997. Current and future approaches to neurotoxicity risk assessment. Ann. N.Y. Acad. Sci. 825:406‐418.
   Slikker, W. Jr., Crump, K.S., Andersen, M.E., and Bellinger, D. 1996. Symposium overview: Biologically based, quantitative risk assessment of neurotoxicants. Fundam. Appl. Toxicol. 29:18‐30.
   Sobotka, T.J., Ekelman, K.B., Slikker, W. Jr., Raffaele, K., and Hattan, D.G. 1996. Food and Drug Administration (FDA) proposed guidelines for neurotoxicological testing of food chemicals. Neurotoxicology 17:825‐836.
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   U.S. Food and Drug Administration (FDA). 1982. Toxicological Principles for the Safety Assessment of Direct Food Additives and Color Additives Used in Foods. Document PB83‐170696, National Technical Information Service, Springfield, Virginia.
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