Behavioral-Functional Teratology

  • K. S. Khera
  • H. C. Grice
  • D. J. Clegg
Part of the Current Issues in Toxicology book series (CI TOXICOLOGY)


During the past decade, there has been intense interest in the development of methods to detect subtle changes resulting from in utero and/or perinatal exposure. Because this interest is concerned with protecting society from potential harm, it reflects an advancement in safety assessment (Christian, 1983a; Riley and Vorhees, 1986). Published reports that maternal exposure to lead (Palmisano et al., 1969) and methyl mercury (Matsumoto et al., 1965; Harada, 1968) could produce central nervous system (CNS) disorders in children spurred research activity and regulatory action in behavioral teratology, with an emphasis on neurotoxic effects. Animal models demonstrating neuro-toxic effects somewhat similar to those of humans were soon reported (Spyker et al., 1972; Butcher et al., 1973; Spyker, 1975; Hutchings, 1983).


Developmental Toxicity Triethylene Glycol Perinatal Exposure Monobutyl Ether Postnatal Effect 
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  1. Adams, J. and Buelke-Sam, J. (1981) Behavioral assessment of the postnatal animal: Testing and methods development. In Developmental Toxicology ( C.A. Kimmel and J. Buelke-Sam, Eds.), pp. 233–258, Raven Press, New York.Google Scholar
  2. Adams, J., Buelke-Sam, J., Kimmel, C.A., Nelson, C.J., Reiter, L.W., Sobotka, T.J., Tilson, H.A., and Nelson, B.K. (1985) Collaborative Behavioral Teratology Study: Protocol design and testing procedures. Neurobehay. Toxicol. Teratol. 7: 579–586.Google Scholar
  3. Alder, S. and Zbinden, G. (1977) Methods for evaluation of physical, neuromuscular, and behavioral development of rats in early postnatal life. In Methods in Prenatal Toxicology ( D. Neubert, H.J. Merker, and T.W. Kwasigroch, Eds.), pp. 175–185, PSG Publishing Co., Littleton, Massachusetts.Google Scholar
  4. Amortegui, A.J., Feinberg, S.S., and Figallo, E.M. (1976) Postnatal effects of chemically induced intrauterine growth retardation on some hematological values in the rat. Biol. Neonate 29: 216–221.PubMedCrossRefGoogle Scholar
  5. Armenti, V.T., Masters, E., Cliver, A., and Johnson, E.M. (1977) Effects of teratogenic insult on fetal lung maturation. Teratology 15: 30A.Google Scholar
  6. Bakke, J.L., Lawrence, N.L., Robinson, S., and Bennett, J. (1976) Lifelong alterations in endocrine function resulting from brief perinatal hypothyroidism in the rat. J. Lab. Clin. Med. 88: 3–13.PubMedGoogle Scholar
  7. Barlow, S.M. and Sullivan, F.M. (1975) Behavioural teratology. In Teratology Trends and Applications ( C.L. Berry and D.E. Poswillo, Eds.), pp. 103–120, Springer-Verlag, Berlin.Google Scholar
  8. Buelke-Sam, J. and Kimmel, C., (1979) Development and standardization of screening methods for behavioral teratology. Teratology 20: 17–29.PubMedCrossRefGoogle Scholar
  9. Buelke-Sam, J., Kimmel, C.A., and Adams, J., Eds. (1985a) Design considerations in screening for behavioral teratogens: Results of the Collaborative Behavioral Teratology Study. Neurobe-hay. Toxicol. Teratol. 7:537–789.Google Scholar
  10. Buelke-Sam, J., Kimmel, C.A., Mains, J., Nelson, C.J., Vorhees, C.V., Wright, D.C., St. Omer, V., Korol, B.A., Butcher, R.E., Geyer, M.A., Holson, J.F., Kutscher, C.L., and Wagner, J.F. (1985b) Collaborative Behavioral Teratology Study: Results. Neurobehay. Toxicol. Teratol. 7: 591–624.Google Scholar
  11. Butcher, R.E. (1976) Behavioral testing as a method for assessing risk. Environ. Health Perspect. 18: 75–78.PubMedCrossRefGoogle Scholar
  12. Butcher, R.E., Scott, W.J., Kazmaier, K., and Ritter, E.J. (1973) Postnatal effects in rats of prenatal treatment with hydroxyurea. Teratology 7: 161–165.PubMedCrossRefGoogle Scholar
  13. Chemoff, N. and Grabowski, C.T. (1971) Responses of the rat fetus to maternal injections of adrenaline and vasopressin. Br. J. Pharmacol. 43: 270–278.Google Scholar
  14. Chester, A., Hallesy, D., and Andrew, F. (1985) Behavioral methods in reproductive and developmental toxicology. Neurobehay. Toxicol. Teratol. 7: 745–752.Google Scholar
  15. Christian, M.S. (1979) Postnatal functional teratology resulting from fetal insult, Dissertation, Thomas Jefferson University, Philadelphia, Pennsylvania.Google Scholar
  16. Christian, M.S. (1983a) Statement of problem. In Assessment of Reproductive and Teratogenic Hazards ( M.S. Christian, W.M. Galbraith, P. Voytek, and M.A. Mehlman, Eds.), pp. 1–4, Princeton Scientific Publishers, Princeton, New Jersey.Google Scholar
  17. Christian, M.S. (1983b) Postnatal alterations of gastrointestinal physiology, hematology, clinical chemistry and other non-CNS parameters. In Teratogenesis and Reproductive Toxicology ( E.M. Johnson and D.M. Kochhar, Eds.), pp. 263–286, Springer-Verlag, Berlin.CrossRefGoogle Scholar
  18. Christian, M.S. (1984) Reproductive toxicity and teratology evaluations of naltrexone. J. Clin. Psychiatry 45: 7–10.PubMedGoogle Scholar
  19. Christian, M.S., Hoberman, A.M., and Lochry, E.A. (1986) Clinical observations and effects predicted in developmental and reproductive toxicity evaluations of naltrexone. Neurotoxicology 7(1):353–354, abstract.Google Scholar
  20. Christian, M.S. and Johnson, E.M. (1978) Prenatal alteration of postnatal gastrointestinal function. Teratology 17: 44A.Google Scholar
  21. Christian, M.S. and Johnson, E.M. (1979a) Postnatal alteration of non-CNS physiology evaluated in rats treated with teratogens during the fetal period. Teratology 19: 23A.Google Scholar
  22. Christian, M.S. and Johnson, E.M. (1979b) Functional teratology of the gastrointestinal tract resulting from fetal insult in the rat. 18th Annual Meeting—Society of Toxicology, p. A119, abstract no. 237.Google Scholar
  23. Committee on the Safety of Medicines (1974) Notes for Guidance on Reproduction Studies, Committee on the Safety of Medicines, Department of Health and Social Security, London, Great Britain.Google Scholar
  24. Danilovitz, M.S., Lightkep, G.E., and Mosher, A.H. (1975) Pediatric study of chronic morphine treatment in rats. Toxicol. Appl. Pharmacol. 33: 169–170.Google Scholar
  25. Daston, G.P. (1981) Effects of cadmium on the prenatal ultrastructural maturation of rat alveolar epithelium. Teratology 23: 75–84.PubMedCrossRefGoogle Scholar
  26. Daston, G.P. and Grabowski, C.T. (1979) Toxic effects of cadmium on the developing rat lung. I. Altered pulmonary surfactant and the induction of respiratory distress syndrome. J. Toxicol. Environ. Health 5: 973–983.PubMedCrossRefGoogle Scholar
  27. DeMeyer, R., Verellen, G., and Gerard, P. (1972) Study of carbohydrate metabolism in the newborn rat as a tool for evaluating effects of drugs administered during pregnancy. In Drugs and Fetal Development ( M.A. Klingberg, A. Abramavici, and J. Chemke, Eds.), pp. 83–96, Plenum Press, New York.Google Scholar
  28. Eguchi, Y., Arishima, K., Morikawa, Y., and Hashimoto, Y. (1976) Changes in the weight of the adrenal glands and in the concentration of plasma corticosterone in perinatal rats after prenatal treatment with estradiol benzoate. J. Endocrinol. 69: 427–431.PubMedCrossRefGoogle Scholar
  29. Elsner, J. (1986) New concepts in assessing behavioral toxicology. In Safety Evaluation and Regulation of Chemicals, 3, ( F. Homburger, Ed.), pp. 62–69, Karger, Basel.Google Scholar
  30. EPA (Environmental Protection Agency) (1984) Proposed guidelines for the health assessment of suspect developmental toxicants. Fed. Regist. 49:46324–46331. ’Google Scholar
  31. EPA (Environmental Protection Agency) (1985) Scientific Rationale for the Selection of Toxicity Testing Methods. II. Teratology, Immunotoxicology and Inhalation Toxicology ( M.G. Ryon andGoogle Scholar
  32. D.S. Sawhney, Eds.), pp. 30–36, National Technical Information Service, ORNL–6094; EPA–560/6–84–004, Springfield, Virginia.Google Scholar
  33. EPA (Environmental Protection Agency) (1986) Triethylene glycol monomethyl, monethyl, and monobutyl ethers; proposed test rule. Fed. Regist. 51: 17883–17892.Google Scholar
  34. Faridy, E. (1975) Effect of maternal malnutrition on surface activity of fetal lungs in rats. J. Appl. Physiol. 39: 535–540.Google Scholar
  35. FDA (Food and Drug Administration) (1966) Guidelines for Reproduction Studies for Safety Evaluation of Drugs for Human Use, U.S. Food and Drug Administration, Washington, D.C.Google Scholar
  36. FDA (Food and Drug Administration) (1970) Advisory Committee on Protocols for Safety Evaluations: Panel on Reproduction Report on Reproduction Studies in the Safety Evaluation of Food Additives and Pesticide Residues. Toxicol. Appl. Pharmacol. 16: 264–269.CrossRefGoogle Scholar
  37. FDA (Food and Drug Administration) (1984) Final Report of Task Force on Reproductive and Developmental Toxicology, U.S. Food and Drug Administration, Washington, D.C.Google Scholar
  38. Grabowski, C.T. (1976) Postnatal effects on rats of prenatal exposure to carbon monoxide. Teratology 13: 23A.Google Scholar
  39. Grabowski, C.T. (1979) An analysis of the causes of perinatal deaths induced by prenatal exposure to Mirex. Teratology 19: 27A.Google Scholar
  40. Grabowski, C.T. and Payne, D.B. (1980) An electrocardiographic study of cardiovascular problems in Mirex-fed rat fetuses. Teratology 22: 167–177.PubMedCrossRefGoogle Scholar
  41. Grabowski, C.T. and Turnstall, A.C. (1977) An electrocardiographic study of rat fetuses treated with trypan blue. Teratology 15: 32A.Google Scholar
  42. Grant, L.D. (1976) Research strategies for behavioral teratology studies. Environ. Health Perspect. 18: 85–94.PubMedCrossRefGoogle Scholar
  43. Harada, Y. (1968) Infantile Minamata disease. In Minamata Disease, pp. 73–91, Univ. Japan Study Group of Minamata Disease.Google Scholar
  44. Hill, R. (1986) Commonly prescribed drugs and fetal development, malnutrition and neurological development in the fetus and child. Neurotoxicology 7(1):358–359, abstract.Google Scholar
  45. Hill, R.M. and Tennyson, L.M. (1986) Maternal drug therapy: Effect on fetal neonatal growth and neurobehavior. Neurotoxicology 7 (2): 121–139.PubMedGoogle Scholar
  46. Hoffman, D.J. and Campbell, K.I. (1977) Postnatal toxicity of carbon monoxide after pre-and postnatal exposure. Toxicol. Lett. 1: 147–150.CrossRefGoogle Scholar
  47. Hutchings, D.E. (1983) Behavioral teratology: A new frontier in neurobehavioral research. In Teratogenesis and Reproductive Toxicology ( E.M. Johnson and D.M. Kochhar, Eds.), pp. 207–235, Springer-Verlag, Berlin.CrossRefGoogle Scholar
  48. Ison, J. (1978) Reflex inhibition and reflex elicitation by acoustic stimuli differing in abruptness of onset and peak intensity. Anim. Learn. Behan 6: 106–110.CrossRefGoogle Scholar
  49. Ison, J. and Kellog, C.K. (1984) Behavioral analysis of sensory function. Teratology 19: 36–37A.Google Scholar
  50. Jensh, R.P. (1983) Behavioral testing procedures: A review. In Teratogenesis and Reproductive Toxicology ( E.M. Johnson and D.M. Kochar, Eds.), pp. 171–206, Springer-Verlag, Berlin.CrossRefGoogle Scholar
  51. Johnson, E.M. (1964) A histologic study of postnatal vitamin B12 deficiency in the rat. Am. J. Pathol. 44: 73–83.PubMedGoogle Scholar
  52. Johnson, E.M. and Armenti, V.T. (1978) Postnatal effects of prenatal insult on lung development in the rat. Anat. Rec. 190: 432–433.Google Scholar
  53. Johnson, E.M., Staples, R.E., and Hoar, R.M. (1980) Behavioral teratogens—Unfortunate terminology. Neurobehay. Toxicol. Teratol. 2:iv, commentary.Google Scholar
  54. Karotkin, E.H., Kido, M., Redding, R.A., Cashore, W.J., Douglas, W., Stern, L., and Oh, W. (1976) The inhibition of pulmonary maturation in the fetal rabbit by maternal treatment with phenobarbital. Am. J. Obstet. Gynecol. 124: 529–531.PubMedGoogle Scholar
  55. Kavlock, R.J. and Gray, J.A. (1985) Functional evaluation of the kidney in reproductive toxicology screens. J. Am. Coll. Toxicol. 4(6), abstract no. 168.Google Scholar
  56. Kavlock, R.J., Chernoff, N., Rogers, E., Whitehouse, D., Carver, B., Gray, J., and Robinson, K. (1982) An analysis of fetotoxicity using biochemical endpoints of organ differentiation. Teratology 26: 183–194.PubMedCrossRefGoogle Scholar
  57. Kimmel, C.A. (1976) Behavioral teratology: Overview. Environ. Health Perspect. 18: 73.PubMedCrossRefGoogle Scholar
  58. Kimmel, C.A., Ed. (1977) Final Report of the Committee on Postnatal Evaluation of Animals Subjected to Insult during Development. National Institute of Environmental Health Sciences, Research Triangle Park, North Carolina.Google Scholar
  59. Kimmel, C.A., Buelke-Sam, J., and Adams, J. (1985) Collaborative Behavioral Teratology Study: Implications, current applications and future directions. Neurobehay. Toxicol. Teratol. 7: 669–673.Google Scholar
  60. Kimmel, C.A., Buelke-Sam, J., Adams, J., Reiter, L.W., Sobotka, T.J., and Tilson, J.A. (1983) An interlaboratory comparison of selected methods in a behavioral teratology protocol. Teratology 27: 57–58A.CrossRefGoogle Scholar
  61. Lochry, E.A. (1985) Application of behavioral evaluations in reproductive screens: Methodological and practical considerations. J. Am. Coll. Toxicol. 4(6), abstract no. 167.Google Scholar
  62. Lochry, E.A., Hoberman, A.M., and Christian, M.S. (1984a) Positive correlation of pup body weight with other commonly used developmental landmarks. Teratology 29: 44A.Google Scholar
  63. Lochry, E.A., Hoberman, A.M., and Christian, M.S. (1984b) Comparative sensitivity of commonly used developmental landmarks and pup body weight. Presented at the European Teratology Society Meeting, Koningshof, The Netherlands, September 1984.Google Scholar
  64. Lochry, E.A., Hoberman, A.M., and Christian, M.S. (1986) Standardization and application of behavioral teratology screens. In Safety Evaluation and Regulation of Chemicals, 3, ( F. Horn-burger, Ed.), pp. 49–61, S. Karger, Basel.Google Scholar
  65. Lucier, G.W. (1976) Perinatal development of conjugative enzyme systems. Environ. Health Perspect. 18: 25–34.PubMedCrossRefGoogle Scholar
  66. Masterpasqua, F., Chapman, R.H., and Lore, R.K. (1976) The effects of prenatal psychological stress on the sexual behavior and reactivity of male rats. Dey. Psychobiol. 9: 403–411.CrossRefGoogle Scholar
  67. Matsumoto, H.G., Koya, G., and Takeuchi, T. (1965) Fetal Minamata disease. A neuropathological study of two cases of intrauterine intoxication by a methyl-mercury compound. J. Neuropathol. Exp. Neurol. 24: 563–574.PubMedCrossRefGoogle Scholar
  68. MHW (Ministry of Health and Welfare) (1984) Information on the Guidelines of Toxicity Studies Required for Applications for Approval to Manufacture (Import) Drugs… (Part I), Notification No. 118, Japanese Pharmaceutical Affairs Bureau, Ministry of Health and Welfare, Tokyo, Japan.Google Scholar
  69. MHW (Ministry of Health and Welfare) (1975) On Animal Experimental Methods for Testing the Effects of Drugs on Reproduction, Pharmaceutical and Supply Bureau, Ministry of Health and Welfare, Tokyo, Japan.Google Scholar
  70. Mukherjee, A.B., Chan, M., Waite, R., Metzger, M.I., and Jaffee, S.J. (1975) Inhibition of RNA synthesis by acetyl salicylate and actinomycin-D during early development in the mouse. Pediatr. Res. 9: 652–657.PubMedCrossRefGoogle Scholar
  71. Neubert, D., Merker, H.-J., and Kwasigroch, T.E., Eds. (1977) Evaluation of postnatal manifestation of prenatally-induced lesions. In Methods in Prenatal Toxicology: Evaluation of Embryotoxic Effects in Experimental Animals, Teratology Workshop, pp. 166–200, PSG Publishing Co., Littleton, Massachusetts.Google Scholar
  72. Newman, L.M. and Johnson, E.M. (1983) Abnormal lung function induced by prenatal insult. In Teratogenesis and Reproductive Toxicology ( E.M. Johnson and D.M. Kochhar, Eds.), pp. 237–261, Springer-Verlag, Berlin.CrossRefGoogle Scholar
  73. Newman, L.M., Johnson, E.M., and Armenti, V.T. (1978) Effect of prenatal vitamin A on neonatal respiratory frequency and 02 consumption in the Long-Evans’ rat. Teratology 17: 44A.Google Scholar
  74. Nolen, G.A. (1985) Developmental landmarks—Useful or not? J. Am. Coll. Toxicol. 4(6), abstract no. 162.Google Scholar
  75. Norton, S. (1986) Behavioral changes in preweaning and adult rats exposed prenatally to low ionizing radiation. Toxicol. Appl. Pharmacol. 83: 240–249.PubMedCrossRefGoogle Scholar
  76. Palmisano, RA., Sneed, R.C., and Cassady, G. (1969) Untaxed whiskey and fetal lead exposure. J. Pediatr. 75: 869–872.PubMedCrossRefGoogle Scholar
  77. Riley, E.P. and Vorhees, C.V. (1986) Handbook of Behavioral Teratology, pp. 1–522, Plenum Press, New York.CrossRefGoogle Scholar
  78. Roberts, D.W. and Chapman, J.R. (1981) Concepts essential to the assessment of toxicity to the developing immune system. In Developmental Toxicology ( C.A. Kimmel and J. Buelke-Sam, Eds.), pp. 167–189, Raven Press, New York.Google Scholar
  79. Robertson, L.D., Swaiman, K.F., and Ptacek, L.J. (1986a) Methodology for follow up of children at risk for growth deficiencies due to antiepileptic drug (AED) exposure during pregnancy: A population based study. Neurotoxicology 7(1):359, abstract.Google Scholar
  80. Robertson, L.D., Swaiman, K.F., and Ptacek, L.J. (1986b) Fetal anticonvulsant drug exposure: A population based study. Neurotoxicology 7 (2): 413–419.PubMedGoogle Scholar
  81. Radier, P.M. (1976) Critical periods for behavior anomalies in mice. Environ. Health Perspect. 18: 79–83.CrossRefGoogle Scholar
  82. Rodier, P.M. (1978) Behavioral teratology. In Handbook of Teratology, Vol. 4, Research Procedures and Data Analysis ( J.G. Wilson and F.C. Fraser, eds.), pp. 397–428, Plenum Press, New York.Google Scholar
  83. Schmidt, R.R. (1984) Altered development of immunocompetence following prenatal or cornbined prenatal-postnatal insult: A timely review. J. Am. Coll. Toxicol. 3: 57–72.CrossRefGoogle Scholar
  84. Schmidt, R.R. and Abbott, P.K. (1983) Altered postnatal mitogenic responsiveness of adult rat splenic lymphocytes following in utero exposure to corn oil. Teratology 27: 411–416.PubMedCrossRefGoogle Scholar
  85. Snell, J. (1977) Effect of prenatal exposure to methylmercury on perinatal carbohydrate metabolism in the rat, p. 13, International Congress of Toxicology, Toronto, Canada.Google Scholar
  86. Snell, K., Ashby, S.L., and Barton, S.J. (1977) Disturbances of perinatal carbohydrate metabolism in rats exposed to methylmercury in utero. Toxicology 8: 277–283.PubMedCrossRefGoogle Scholar
  87. Sparber, S.B. (1986a) Developmental effects of narcotics. Neurotoxicology 7(1):357, abstract. Sparber, S.B. (1986b) Developmental effects of narcotics. Neurotoxicology 7 (2): 325–348.Google Scholar
  88. Spyker, J.M. (1975) Behavioral teratology and toxicology. In Behavioral Toxicology ( B. Weiss and V.G. Laties, Eds.), pp. 311–349, Plenum Press, New York.Google Scholar
  89. Spyker, J.M., Sparber, S.B., and Goldberg, A.M. (1972) Subtle consequences of methylmercury exposure: Behavioral deviations in offspring of treated mothers. Science 177: 621–623.PubMedCrossRefGoogle Scholar
  90. Stanley, N.N., Alper, R., Cunningham, E.L., Cherniack, N.S., and Kefalides, N.A. (1975) Effects of a molecular change in collagen on lung structure and mechanical function. J. Clin. Invest. 55: 1195–1201.PubMedCrossRefGoogle Scholar
  91. Sullivan, F.M. and Barlow, S.M. (1976) Behavioural teratology: Some problems in assessment of post-natal development and behaviour. In Advances in the Detection of Congenital Malformation ( E.B. van Julsingha, J.M. Tesh, and G.M. Fara, Eds.), pp. 87–93, European Teratology Society, Kent, England.Google Scholar
  92. Tanimura, T. (1986a) Collaborative studies on behavioral teratology by 46 laboratories in Japan. Neurotoxicology 7(1):370, abstract.Google Scholar
  93. Tanimura, T. (1986b) Collaborative studies on behavioral teratology in Japan. Neurotoxicology 7 (2): 35–46.PubMedGoogle Scholar
  94. Tilson, H.A. and Crammer, J.M., Eds. (1986) Neurotoxicology in the fetus and child. Neurotoxicology 7(2).Google Scholar
  95. Vojnik, C. and Hurley, L.S. (1977) Abnormal prenatal lung development resulting from maternal zinc deficiency in rats. J. Nutr. 107: 862–872.PubMedGoogle Scholar
  96. Vorhees, C.V. (1985) Comparison of the Collaborative Behavioral Teratology Study and Cincinnati behavioral teratology test batteries. Neurobehay. Toxicol. Teratol. 7: 625–633.Google Scholar
  97. Werboff, J. and Gottlieb, J.S. (1963) Drugs in pregnancy: Behavioral teratology. Obstet. Gynecol. Surv. 18: 420.Google Scholar
  98. Werboff, J., Gottlieb, J.S., Dembicki, E.L., and Havlena, J. (1961) Postnatal effect of antidepressant drugs administered during gestation. Exp. Neurol. 3: 542–555.PubMedCrossRefGoogle Scholar
  99. West, G.L. (1985) Considerations of sensory motor coordination tests during growth and development. J. Am. Coll. Toxicol. 4(6), abstract no. 163.Google Scholar
  100. Wilson, J.G. (1973) Environment and Birth Defects, p. 28, Academic Press, New York.Google Scholar

Copyright information

© Springer-Verlag New York Inc. 1989

Authors and Affiliations

  • K. S. Khera
    • 1
  • H. C. Grice
    • 2
  • D. J. Clegg
    • 1
  1. 1.Health Protection BranchHealth and Welfare CanadaOttawaCanada
  2. 2.NepeanCanada

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