A.N. Worden – författare

Reproduction and fetal development in humans and experimental animals may be adversely affected by a wide range of drugs and environmental agents. They may be toxic in the parental generation leading to impaired germ cell formation, loss of reproductive poten­ tial and infertility following chronic exposure. Deviant fetal development occurs as a consequence of cellular damage at sensi­ tive stages in development. Changes seen range from intrauterine mortality and structural malformation to growth retardation with physiological and behavioural defects. Concepts on the mechanism of action of teratogens are discussed with reference to some better-known agents. Presently, regulatory authorities prefer whole animal studies in predictive safety evaluation of substances to which a pregnant woman may be exposed. Tests are conducted over one or more generations and are designed to study the influence of test com­ pounds upon general reproductive performance, fertility, fetal development and perinatal and postnatal behaviour. Experiments are designed to permit compounds to be tested under conditions resembling expected human exposure. Small rodents and rabbits are preferred species on account of their convenience as laboratory animals and the available knowledge regarding their reproductive behaviour, fetal development and known sensitivity to human teratogens.

A. N. WORDEN, D. V. PARKE AND J. MARKS THE BACKGROUND There is nothing new about the fact that chemical substances derived either from natural products or by synthetic means .. can give rise to toxicity in animals and human beings, and that they must be subjected to controls. The earliest writings speak of such toxicity and, from the times of ancient Egypt and in the Old Tes­ tament, controls have existed[l]. In the Middle Ages Paracelsus (1493-1541) noted that "All things are poisons, for there is nothing without poisonous qualities. It is only the dose which makes a thing a poison", and hence he stressed the importance of dose relative to toxic reactions [ 2] . Most of the early controls concentrated on substances that were to be deliberately administered to the human subject in the form of medicines. Legislation for many centuries was mainly con­ cerned with regulating the activities of apothecaries and physicians. The Royal College of Physicians, for example, was originally established to control the activities of physicians within London. Among the controls which it exerted was that over the use of medicinal substances. Such controls were, however, poor, based as they were on hearsay evidence of toxicity. For many centuries no means existed for the accurate determination of toxicity.

Reproduction and fetal development in humans and experimental animals may be adversely affected by a wide range of drugs and environmental agents. They may be toxic in the parental generation leading to impaired germ cell formation, loss of reproductive poten­ tial and infertility following chronic exposure. Deviant fetal development occurs as a consequence of cellular damage at sensi­ tive stages in development. Changes seen range from intrauterine mortality and structural malformation to growth retardation with physiological and behavioural defects. Concepts on the mechanism of action of teratogens are discussed with reference to some better-known agents. Presently, regulatory authorities prefer whole animal studies in predictive safety evaluation of substances to which a pregnant woman may be exposed. Tests are conducted over one or more generations and are designed to study the influence of test com­ pounds upon general reproductive performance, fertility, fetal development and perinatal and postnatal behaviour. Experiments are designed to permit compounds to be tested under conditions resembling expected human exposure. Small rodents and rabbits are preferred species on account of their convenience as laboratory animals and the available knowledge regarding their reproductive behaviour, fetal development and known sensitivity to human teratogens.