D.V. Parke – författare

This volume grew out of work on Berkeley which was presented in a dissertation several years ago. Though now much revised and greatly expanded. particularly in respect of the theory of concepts, a good part of the present text rests on this earlier foundation. I therefore gladly take this opportunity to express my appreciation to my teachers both at Indiana University and at McGill, and especially to Professor Newton Stallknecht who directed my dissertation. For permission to quote from the Berkeley manuscripts in their keeping, I have first to thank the Trustees of the British Museum, and the Board of Trinity College Dublin. I wish further to thank the Bodleian Library, Oxford for allowing me to quote from their collection of Locke manu­ scripts. Also I am grateful to the Editor of Filoso/ia for letting me use excerpts from an article that first appeared in the Stu'di Internazionali di Filoso/ia, and to George Allen and Unwin. Publishers, for permission to quote a long passage from Bertrand Russell's Analysis 0/ Mind. From thesis project to published book, my research on the Berkeley manuscripts has been made possible by the generous and timely support of the Canada Council. Finally. I wish to thank Mrs. Anne Hillier for preparing the manuscript with great patience and skill.

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.

This volume grew out of work on Berkeley which was presented in a dissertation several years ago. Though now much revised and greatly expanded. particularly in respect of the theory of concepts, a good part of the present text rests on this earlier foundation. I therefore gladly take this opportunity to express my appreciation to my teachers both at Indiana University and at McGill, and especially to Professor Newton Stallknecht who directed my dissertation. For permission to quote from the Berkeley manuscripts in their keeping, I have first to thank the Trustees of the British Museum, and the Board of Trinity College Dublin. I wish further to thank the Bodleian Library, Oxford for allowing me to quote from their collection of Locke manu­ scripts. Also I am grateful to the Editor of Filoso/ia for letting me use excerpts from an article that first appeared in the Stu''di Internazionali di Filoso/ia, and to George Allen and Unwin. Publishers, for permission to quote a long passage from Bertrand Russell''s Analysis 0/ Mind. From thesis project to published book, my research on the Berkeley manuscripts has been made possible by the generous and timely support of the Canada Council. Finally. I wish to thank Mrs. Anne Hillier for preparing the manuscript with great patience and skill.

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.