Principles of Teratology

The principles of teratology have been articulated by Wilson (104). The first principle is that teratogens act with specificity. A teratogen produces a specific abnormality or constellation of abnormalities. For example thalidomide produces phocomelia/ and valproic acid produces neural tube defects. This specificity also applies to species because drug effects may be seen in one species and not in another. The best example is cortisol which produces cleft palate in mice but not in humans. 

The fourth principle is that the effect that a teratogenic agent has on a developing fetus depends upon the stage during development when the fetus is exposed. From conception to implantation there is an all-or-nothing effect/ in that the embryO/ if exposed to a teratogeii/ either survives unharmed or dies. 

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James Wilson (in 1959) proposed six principles of teratology. A simplified version of these is as follows ... 

Two of the most questionable practices by those who are not familiar with the principles of teratology are (1) making lists of chemicals or other agents known or suspected to be teratogenic or otherwise toxic to the embryo and fetus and (2) assuming that the results of animal studies mimic those in human beings. 

How then can it be that a compound which has no detectable teratogenic activity in either animal or human studies be held responsible for human congenital malformations The history of Bendectin can be traced to ignorance of the principles of teratology, compounded by precedential case law following the first erroneous decision and to two articles appearing in the popular press. In the September 1979 issue of the National Enquirer, the following was published ... 

Brent RL, Beckman DA. 1992. Principles of teratology. In Evans MI, ed. Reproductive risks and prenatal diagnosis. Norwalk, CT Appleton Lange, 43-68. 

Vorhees CV (1986) Principles of behavioural teratology. In Riley EP Voorhees CV ed. Handbook of behavioural teratology. New York, Plenum Press, pp 23-66. 

Source Wilson, J. G. (1977) Curent status of teratology. In Wilson, J. G., and Fraser, F. C. (Eds.). Hand-bood of Teratology, Vol. 1 General Principles and Etiology, Plenum Press, New York, 1977, pp. 47-74. 

Wilson, J.G. (1977). Current status of teratology general principles and mechanisms derived from animal studies. In... 

Basic problems of animal-to-human extrapolation are in the OTA s report (op. cit.) and comprehensively treated in Edward Calabrese, Principles of Animal Extrapolation (John Wiley and Sons New York, 1983). The particular problem of extrapolation of teratology data from animals to humans is concisely discussed by V. Frankos in his paper FDA perspectives in the use of teratology data for human risk assessment (Fundamental and Applied Toxicology, Vol. 5, 1985, pp 615-25). 

Roels H, Hubermont G, Buchet JP, Lauwerys R (1978) Placental transfer of lead, mercury, cadmium, and carbon monoxide in women. III. Factors influencing the accumulation of heavy metals in the placenta and the relationship between metal concentration in the placenta and in maternal and cord blood. Environ. Res. 16 236 Wilson JG (1973) Environment and birth defects. Academic Press, New York - London Wilson JG (1977) Current status in teratology - general principles and mechanisms derived from animal studies. In Handbook of teratology, Vol. 1, eds. Wilson JG, Fraser FC, Plenum Press, New York, p. 75... 

Kamofsky, D. (1965). Mechanisms of action of certain growth-inhibiting drugs. In Teratology Principles and Techniques (Wilson, J. and Warkany, J., Eds.). University of Chicago Press, pp. 185-213. 

Wilson JG, Warkany J (1965) Teratology principles and techniques (Lectures and demonstrations given at the first workshop in teratology. University of Florida, February 2-8, 1964). University of Chicago Press, Chicago... 

Wilson JG (1965) Methods for administering agents and detecting malformations in experimental animals. In Wilson JG, Warkany J (eds) Teratology principles and techniques. University of Cliicago Press, Chicago, pp 262-277... 

Wilson JG (1965) Embryological considerations in teratology. In Wilson JG Warkany J eds. Teratology Principles and techniques. Chicago, IL, University of Chicago Press. 

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