Skip to main content
NCBI home page
Environmental Health Perspectives logoLink to Environmental Health Perspectives
. 1987 Dec;76:155–161. doi: 10.1289/ehp.8776155

Risk assessment for neurobehavioral toxicity.

D E McMillan 1
PMCID: PMC1474485  PMID: 3447892

Abstract

A study by the National Academy of Sciences/National Research Council (NAS/NRC) found neurobehavioral toxicity to be one of the areas where almost no data are available for the assessment of toxicity. Using the NAS/NRC report and a data base from the American Conference of Government Industrial Hygienists (ACGIH), an estimate of the number of neurobehavioral toxins in commercial chemicals can be made. Although the assumption made in making such a calculation may be invalid, the exercise suggests that the number of neurobehavioral toxins may be quite large. There does seem to be general agreement as to what type of neurobehavioral test procedures are appropriate for regulatory purposes. Select committees have consistently recommended the use of test batteries that include schedule-controlled behavior, motor activity, and neuropathological examination following in vivo perfusion, for regulatory purposes. Alkyltin data developed from such a battery were applied to the risk assessment model employed by the United States Environmental Protection Agency (EPA) in their calculations of acceptable daily intake. Using this test battery and the EPA risk assessment model, the acceptable daily intake calculated is of the same order of magnitude as the total limit values established by the ACGIH. A number of special issues in neurobehavioral toxicity also are discussed, including the definition of adverse neurobehavioral toxic effects, species extrapolation, correlation of behavior and neuropathology, alternative methods, and quality of life issues.

Full text

PDF
155

Selected References

These references are in PubMed. This may not be the complete list of references from this article.

  1. Aldridge W. N., Brown A. W., Brierley J. B., Verschoyle R. D., Street B. W. Brain damage due to trimethyltin compounds. Lancet. 1981 Sep 26;2(8248):692–693. doi: 10.1016/s0140-6736(81)91021-7. [DOI] [PubMed] [Google Scholar]
  2. Anger W. K. Neurobehavioral testing of chemicals: impact on recommended standards. Neurobehav Toxicol Teratol. 1984 Mar-Apr;6(2):147–153. [PubMed] [Google Scholar]
  3. Bouldin T. W., Goines N. D., Bagnell R. C., Krigman M. R. Pathogenesis of trimethyltin neuronal toxicity. Ultrastructural and cytochemical observations. Am J Pathol. 1981 Sep;104(3):237–249. [PMC free article] [PubMed] [Google Scholar]
  4. Brown A. W., Aldridge W. N., Street B. W., Verschoyle R. D. The behavioral and neuropathologic sequelae of intoxication by trimethyltin compounds in the rat. Am J Pathol. 1979 Oct;97(1):59–82. [PMC free article] [PubMed] [Google Scholar]
  5. Bushnell P. J., Evans H. L. Effects of trimethyltin on homecage behavior of rats. Toxicol Appl Pharmacol. 1985 Jun 15;79(1):134–142. doi: 10.1016/0041-008x(85)90375-8. [DOI] [PubMed] [Google Scholar]
  6. Chang L. W., Dyer R. S. A time-course study of trimethyltin induced neuropathology in rats. Neurobehav Toxicol Teratol. 1983 Jul-Aug;5(4):443–459. [PubMed] [Google Scholar]
  7. Chang L. W., Dyer R. S. Trimethyltin induced pathology in sensory neurons. Neurobehav Toxicol Teratol. 1983 Nov-Dec;5(6):673–696. [PubMed] [Google Scholar]
  8. Chang L. W., Tiemeyer T. M., Wenger G. R., McMillan D. E. Neuropathology of mouse hippocampus in acute trimethyltin intoxication. Neurobehav Toxicol Teratol. 1982 Mar-Apr;4(2):149–156. [PubMed] [Google Scholar]
  9. Chang L. W., Tiemeyer T. M., Wenger G. R., McMillan D. E. Neuropathology of trimethyltin intoxication. III. Changes in the brain stem neurons. Environ Res. 1983 Apr;30(2):399–411. doi: 10.1016/0013-9351(83)90226-8. [DOI] [PubMed] [Google Scholar]
  10. Chang L. W., Tiemeyer T. M., Wenger G. R., McMillan D. E., Reuhl K. R. Neuropathology of trimethyltin intoxication. I. Light microscopy study. Environ Res. 1982 Dec;29(2):435–444. doi: 10.1016/0013-9351(82)90044-5. [DOI] [PubMed] [Google Scholar]
  11. Chang L. W. Trimethyltin induced hippocampal lesions at various neonatal ages. Bull Environ Contam Toxicol. 1984 Sep;33(3):295–301. doi: 10.1007/BF01625546. [DOI] [PubMed] [Google Scholar]
  12. Chang L. W., Wenger G. R., McMillan D. E. Neuropathology of trimethyltin intoxication. IV. Changes in the spinal cord. Environ Res. 1984 Jun;34(1):123–134. doi: 10.1016/0013-9351(84)90082-3. [DOI] [PubMed] [Google Scholar]
  13. DEWS P. B. The measurement of the influence of drugs on voluntary activity in mice. Br J Pharmacol Chemother. 1953 Mar;8(1):46–48. doi: 10.1111/j.1476-5381.1953.tb00749.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  14. Johnson C. T., Dunn A., Robinson C., Walsh T. J., Swartzwelder H. S. Alterations in regulatory and locomotor behaviors following trimethyltin exposure in the rat: a time and dose analysis. Neurosci Lett. 1984 Jun 15;47(2):99–106. doi: 10.1016/0304-3940(84)90413-0. [DOI] [PubMed] [Google Scholar]
  15. McMillan D. E., Chang L. W., Idemudia S. O., Wenger G. R. Effects of trimethyltin and triethyltin on lever pressing, water drinking and running in an activity wheel: associated neuropathology. Neurobehav Toxicol Teratol. 1986 Sep-Oct;8(5):499–507. [PubMed] [Google Scholar]
  16. McMillan D. E., Wenger G. R., Brocco M. J., Idemudia S. O., Chang L. W. Effects of trialkyltins on the schedule-controlled behavior of the pigeon. Neurotoxicol Teratol. 1987 Jan-Feb;9(1):67–74. doi: 10.1016/0892-0362(87)90072-9. [DOI] [PubMed] [Google Scholar]
  17. McMillan D. E., Wenger G. R. Neurobehavioral toxicology of trialkyltins. Pharmacol Rev. 1985 Dec;37(4):365–379. [PubMed] [Google Scholar]
  18. Rastogi S. K., McMillan D. E., Wenger G. R., Chang L. W. Effects of triethyltin and its interaction with d-amphetamine and chlorpromazine on responding under a multiple schedule of food presentation in rats. Neurobehav Toxicol Teratol. 1985 May-Jun;7(3):239–242. [PubMed] [Google Scholar]
  19. Reiter L. W., MacPhail R. C. Motor activity: a survey of methods with potential use in toxicity testing. Neurobehav Toxicol. 1979;1 (Suppl 1):53–66. [PubMed] [Google Scholar]
  20. Reiter L. Behavioral toxicology: effects of early postnatal exposure to neurotoxins on development of locomotor activity in the rat. J Occup Med. 1977 Mar;19(3):200–204. [PubMed] [Google Scholar]
  21. Ruppert P. H., Walsh T. J., Reiter L. W., Dyer R. S. Trimethyltin-induced hyperactivity: time course and pattern. Neurobehav Toxicol Teratol. 1982 Mar-Apr;4(2):135–139. [PubMed] [Google Scholar]
  22. Walsh T. J., Miller D. B., Dyer R. S. Trimethyltin, a selective limbic system neurotoxicant, impairs radial-arm maze performance. Neurobehav Toxicol Teratol. 1982 Mar-Apr;4(2):177–183. [PubMed] [Google Scholar]
  23. Wenger G. R., McMillan D. E., Chang L. W. Behavioral effects of trimethyltin in two strains of mice. I. Spontaneous motor activity. Toxicol Appl Pharmacol. 1984 Mar 30;73(1):78–88. doi: 10.1016/0041-008x(84)90055-3. [DOI] [PubMed] [Google Scholar]
  24. Wenger G. R., McMillan D. E., Chang L. W. Behavioral effects of trimethyltin in two strains of mice. II. Multiple fixed ratio, fixed interval. Toxicol Appl Pharmacol. 1984 Mar 30;73(1):89–96. doi: 10.1016/0041-008x(84)90056-5. [DOI] [PubMed] [Google Scholar]
  25. Wenger G. R., McMillan D. E., Chang L. W., Zitaglio T., Hardwick W. C. The effects of triethyltin and trimethyltin in rats responding under a DRL schedule of reinforcement. Toxicol Appl Pharmacol. 1985 Apr;78(2):248–258. doi: 10.1016/0041-008x(85)90288-1. [DOI] [PubMed] [Google Scholar]

Articles from Environmental Health Perspectives are provided here courtesy of National Institute of Environmental Health Sciences

RESOURCES