Skip to main content
Environmental Health Perspectives logoLink to Environmental Health Perspectives
. 1985 Sep;61:55–67. doi: 10.1289/ehp.856155

Species sensitivities and prediction of teratogenic potential.

J L Schardein, B A Schwetz, M F Kenel
PMCID: PMC1568765  PMID: 3905381

Abstract

Many chemicals shown to be teratogenic in laboratory animals are not known to be teratogenic in humans. However, it remains to be determined if the unresponsiveness of humans is due to lessened sensitivity, to generally subteratogenic exposure levels, or to the lack of an appropriate means of identifying human teratogens. On the other hand, with the exception of the coumarin anticoagulant drugs, those agents well accepted as human teratogens have been shown to be teratogenic in one or more laboratory species. Yet, no single species has clearly distinguished itself as being more advantageous in the detection of human teratogens over any other. Among the species used for testing, the rat and mouse most successfully model the human reaction, but the rabbit is less likely than other species to give a false positive finding. Among species less commonly used for testing, primates offered a higher level of predicability than others. Regarding concordance of target malformations, the mouse and rat produced the greatest number of concordant defects, but they also were responsible for the most noncorcordant responses as well. Since no other species is clearly more predictive of the human response, it is concluded that safety decisions should be based on all reproductive and developmental toxicity data in light of the agent's known pharmacokinetic, metabolic and toxicologic parameters.

Full text

PDF
55

Selected References

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

  1. Barlow S. M., Knight A. F., Sullivan F. M. Diazepam-induced cleft palate in the mouse: the role of endogenous maternal corticosterone. Teratology. 1980 Apr;21(2):149–155. doi: 10.1002/tera.1420210203. [DOI] [PubMed] [Google Scholar]
  2. Barlow S. M., Morrison P. J., Sullivan F. M. Effects of acute and chronic stress on plasma corticosterone levels in the pregnant and non-pregnant mouse. J Endocrinol. 1975 Jul;66(1):9O–99. doi: 10.1677/joe.0.0660093. [DOI] [PubMed] [Google Scholar]
  3. Book S. A. Scaling toxicity from laboratory animals to people: an example with nitrogen dioxide. J Toxicol Environ Health. 1982 May-Jun;9(5-6):719–725. doi: 10.1080/15287398209530199. [DOI] [PubMed] [Google Scholar]
  4. Brown N. A., Fabro S. The value of animal teratogenicity testing for predicting human risk. Clin Obstet Gynecol. 1983 Jun;26(2):467–477. doi: 10.1097/00003081-198306000-00028. [DOI] [PubMed] [Google Scholar]
  5. Buresh J. J., Urban T. J. Palatal abnormalities induced by cortisone and corticosterone in the rat. J Acad Gen Dent. 1970 Jun;18(2):34–37. [PubMed] [Google Scholar]
  6. DIAMOND I., ANDERSON M. M., McCREADIE S. R. Transplacental transmission of busulfan (myleran) in a mother with leukemia. Production of fetal malformation and cytomegaly. Pediatrics. 1960 Jan;25:85–90. [PubMed] [Google Scholar]
  7. Ferm V. H. The use of the golden hamster in experimental teratology. Lab Anim Care. 1967 Oct;17(5):452–462. [PubMed] [Google Scholar]
  8. Flynt J. W., Jr Techniques for assessing teratogenic effects: epidemiology. Environ Health Perspect. 1976 Dec;18:117–123. doi: 10.1289/ehp.7618117. [DOI] [PMC free article] [PubMed] [Google Scholar]
  9. GREENBERG L. H., TANAKA K. R. CONGENITAL ANOMALIES PROBABLY INDUCED BY CYCLOPHOSPHAMIDE. JAMA. 1964 May 4;188:423–426. doi: 10.1001/jama.1964.03060310023005. [DOI] [PubMed] [Google Scholar]
  10. Garrett M. J. Letter: Teratogenic effects of combination chemotherapy. Ann Intern Med. 1974 May;80(5):667–667. doi: 10.7326/0003-4819-80-5-667_1. [DOI] [PubMed] [Google Scholar]
  11. Gralla E. J., McIlhenny H. M. Studies in pregnant rats, rabbits and monkeys with lithium carbonate. Toxicol Appl Pharmacol. 1972 Mar;21(3):428–433. doi: 10.1016/0041-008x(72)90163-9. [DOI] [PubMed] [Google Scholar]
  12. Hansen D. K., Hodes M. E. Metabolism of phenytoin in teratogenesis-susceptible and -resistant strains of mice. Drug Metab Dispos. 1983 Jan-Feb;11(1):21–24. [PubMed] [Google Scholar]
  13. Hanson J. W., Smith D. W. The fetal hydantoin syndrome. J Pediatr. 1975 Aug;87(2):285–290. doi: 10.1016/s0022-3476(75)80604-4. [DOI] [PubMed] [Google Scholar]
  14. Hemm R. D., Arslanoglou L., Pollock J. J. Cleft palate following prenatal food restriction in mice: association with elevated maternal corticosteroids. Teratology. 1977 Jun;15(3):243–248. doi: 10.1002/tera.1420150305. [DOI] [PubMed] [Google Scholar]
  15. Herbst A. L., Scully R. E. Adenocarcinoma of the vagina in adolescence. A report of 7 cases including 6 clear-cell carcinomas (so-called mesonephromas). Cancer. 1970 Apr;25(4):745–757. doi: 10.1002/1097-0142(197004)25:4<745::aid-cncr2820250402>3.0.co;2-2. [DOI] [PubMed] [Google Scholar]
  16. Herbst A. L., Ulfelder H., Poskanzer D. C. Adenocarcinoma of the vagina. Association of maternal stilbestrol therapy with tumor appearance in young women. N Engl J Med. 1971 Apr 15;284(15):878–881. doi: 10.1056/NEJM197104222841604. [DOI] [PubMed] [Google Scholar]
  17. Jones K. L., Smith D. W., Ulleland C. N., Streissguth P. Pattern of malformation in offspring of chronic alcoholic mothers. Lancet. 1973 Jun 9;1(7815):1267–1271. doi: 10.1016/s0140-6736(73)91291-9. [DOI] [PubMed] [Google Scholar]
  18. KALTER H. EXPERIMENTAL INVESTIGATION OF TERATOGENIC ACTION. Ann N Y Acad Sci. 1965 Mar 12;123:287–294. doi: 10.1111/j.1749-6632.1965.tb12269.x. [DOI] [PubMed] [Google Scholar]
  19. Kalter H. Dose-response studies with genetically homogeneous lines of mice as a teratology testing and risk-assessment procedure. Teratology. 1981 Aug;24(1):79–86. doi: 10.1002/tera.1420240109. [DOI] [PubMed] [Google Scholar]
  20. Kerber I. J., Warr O. S., 3rd, Richardson C. Pregnancy in a patient with a prosthetic mitral valve. Associated with a fetal anomaly attributed to warfarin sodium. JAMA. 1968 Jan 15;203(3):223–225. [PubMed] [Google Scholar]
  21. Khera K. S. Teratogenic effects of methylmercury in the cat: note on the use of this species as a model for teratogenicity studies. Teratology. 1973 Dec;8(3):293–303. doi: 10.1002/tera.1420080309. [DOI] [PubMed] [Google Scholar]
  22. Klingberg M. A., Papier C. M. Teratoepidemiology. J Biosoc Sci. 1979 Jul;11(3):233–258. doi: 10.1017/s0021932000012323. [DOI] [PubMed] [Google Scholar]
  23. Kocher W. Action and interaction of chemical and genetic factors in teratogenesis of the limb. Birth Defects Orig Artic Ser. 1977;13(1):1–18. [PubMed] [Google Scholar]
  24. Legator M. S., Harper B. L. Animal-human studies: an integrated approach to identifying hazardous chemicals in the workplace. Prog Clin Biol Res. 1982;109:181–202. [PubMed] [Google Scholar]
  25. MELTZER H. J. Congenital anomalies due to attempted abortion with 4-aminopteroglutamic acid. J Am Med Assoc. 1956 Jul 28;161(13):1253–1253. doi: 10.1001/jama.1956.62970130002010a. [DOI] [PubMed] [Google Scholar]
  26. Matsuzawa T., Nakata M., Goto I., Tsushima M. Dietary deprivation induces fetal loss and abortion in rabbits. Toxicology. 1981;22(3):255–259. doi: 10.1016/0300-483x(81)90088-3. [DOI] [PubMed] [Google Scholar]
  27. Milunsky A., Graef J. W., Gaynor M. F., Jr Methotrexate-induced congenital malformations. J Pediatr. 1968 Jun;72(6):790–795. doi: 10.1016/s0022-3476(68)80430-5. [DOI] [PubMed] [Google Scholar]
  28. Mjolnerod O. K., Dommerud S. A., Rasmussen K., Gjeruldsen S. T. Congenital connective-tissue defect probably due to D-penicillamine treatment in pregnancy. Lancet. 1971 Apr 3;1(7701):673–675. doi: 10.1016/s0140-6736(71)92681-x. [DOI] [PubMed] [Google Scholar]
  29. Mulvihill J. J., Priester W. A. Congenital heart disease in dogs: epidemiologic similarities to man. Teratology. 1973 Feb;7(1):73–77. doi: 10.1002/tera.1420070111. [DOI] [PubMed] [Google Scholar]
  30. Omenn G. S. A framework for reproductive risk assessment and surveillance. Teratog Carcinog Mutagen. 1984;4(1):1–14. doi: 10.1002/tcm.1770040103. [DOI] [PubMed] [Google Scholar]
  31. Palmer A. K. Assessment of current test procedures. Environ Health Perspect. 1976 Dec;18:97–104. doi: 10.1289/ehp.761897. [DOI] [PMC free article] [PubMed] [Google Scholar]
  32. Poswillo D. E., Hamilton W. J., Sopher D. The marmoset as an animal model for teratological research. Nature. 1972 Oct 20;239(5373):460–462. doi: 10.1038/239460a0. [DOI] [PubMed] [Google Scholar]
  33. Rall D. P. Relevance of animal experiments to humans. Environ Health Perspect. 1979 Oct;32:297–300. doi: 10.1289/ehp.7932297. [DOI] [PMC free article] [PubMed] [Google Scholar]
  34. Rosa F. W. Teratogenicity of isotretinoin. Lancet. 1983 Aug 27;2(8348):513–513. doi: 10.1016/s0140-6736(83)90538-x. [DOI] [PubMed] [Google Scholar]
  35. SHOTTON D., MONIE I. W. POSSIBLE TERATOGENIC EFFECT OF CHLORAMBUCIL ON A HUMAN FETUS. JAMA. 1963 Oct 5;186:74–75. doi: 10.1001/jama.1963.63710010031022c. [DOI] [PubMed] [Google Scholar]
  36. Schou M., Goldfield M. D., Weinstein M. R., Villeneuve A. Lithium and pregnancy. I. Report from the Register of Lithium Babies. Br Med J. 1973 Apr 21;2(5859):135–136. doi: 10.1136/bmj.2.5859.135. [DOI] [PMC free article] [PubMed] [Google Scholar]
  37. Schwetz B. A., Smith F. A., Staples R. E. Teratogenic potential of ethanol in mice, rats and rabbits. Teratology. 1978 Dec;18(3):385–392. doi: 10.1002/tera.1420180313. [DOI] [PubMed] [Google Scholar]
  38. Siddall R. A. The use of marmosets (Callithrix jacchus) in teratological and toxicological research. Primates Med. 1978;10:215–224. [PubMed] [Google Scholar]
  39. Squire R. A. Ranking animal carcinogens: a proposed regulatory approach. Science. 1981 Nov 20;214(4523):877–880. doi: 10.1126/science.7302565. [DOI] [PubMed] [Google Scholar]
  40. Stadler J., Kessedjian M. J., Perraud J. Use of the New Zealand white rabbit in teratology: incidence of spontaneous and drug-induced malformations. Food Chem Toxicol. 1983 Oct;21(5):631–636. doi: 10.1016/0278-6915(83)90151-5. [DOI] [PubMed] [Google Scholar]
  41. Stephens J. D., Golbus M. S., Miller T. R., Wilber R. R., Epstein C. J. Multiple congenital anomalies in a fetus exposed to 5-fluorouracil during the first trimester. Am J Obstet Gynecol. 1980 Jul 15;137(6):747–749. doi: 10.1016/s0002-9378(15)33259-2. [DOI] [PubMed] [Google Scholar]
  42. Stern L. In vivo assessment of the teratogenic potential of drugs in man. Dev Pharmacol Ther. 1982;4 (Suppl):10–18. doi: 10.1159/000457354. [DOI] [PubMed] [Google Scholar]
  43. Szabo K. T., Brent R. L. Letter: Species differences in experimental teratogenesis by tranquillising agents. Lancet. 1974 Mar 30;1(7857):565–565. doi: 10.1016/s0140-6736(74)92749-4. [DOI] [PubMed] [Google Scholar]
  44. Tuchmann-Duplessis H. The teratogenic risk. Am J Ind Med. 1983;4(1-2):245–258. [PubMed] [Google Scholar]
  45. Vorhees C. V. Behavioral teratogenicity testing as a method of screening for hazards to human health: a methodological proposal. Neurobehav Toxicol Teratol. 1983 Jul-Aug;5(4):469–474. [PubMed] [Google Scholar]
  46. Wagner V. M., Hill J. S., Weaver D., Baehner R. L. Congenital abnormalities in baby born to cytarabine treated mother. Lancet. 1980 Jul 12;2(8185):98–99. doi: 10.1016/s0140-6736(80)92986-4. [DOI] [PubMed] [Google Scholar]
  47. Wilson J. G. Reproduction and teratogenesis: current methods and suggested improvements. J Assoc Off Anal Chem. 1975 Jul;58(4):657–667. [PubMed] [Google Scholar]
  48. Wilson J. G. Use of rhesus monkeys in teratological studies. Fed Proc. 1971 Jan-Feb;30(1):104–109. [PubMed] [Google Scholar]
  49. Wilson J. G. Use of rhesus monkeys in teratological studies. Fed Proc. 1971 Jan-Feb;30(1):104–109. [PubMed] [Google Scholar]
  50. ZANDER J., MULLER H. A. Uber die Methylandrostendiolbehandlung während einer Schwangerschaft. Geburtshilfe Frauenheilkd. 1953 Mar;13(3):216–222. [PubMed] [Google Scholar]
  51. Zackai E. H., Mellman W. J., Neiderer B., Hanson J. W. The fetal trimethadione syndrome. J Pediatr. 1975 Aug;87(2):280–284. doi: 10.1016/s0022-3476(75)80603-2. [DOI] [PubMed] [Google Scholar]

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

RESOURCES