Felix Beck (auth.), Keith Snell (eds.)'s Developmental Toxicology PDF

By Felix Beck (auth.), Keith Snell (eds.)

ISBN-10: 1461597900

ISBN-13: 9781461597902

ISBN-10: 1461597927

ISBN-13: 9781461597926

Since the Nineteen Thirties and the paintings of Hale and Warkany on delivery defects produced by means of diversifications in nutritional nutrition A, it's been recognized that the constructing fetus is especially at risk of hostile impacts within the surroundings. . reviews of malformations at start remained principally within the fingers of paediatricians who, for example, quick tested the con­ nection among rubella an infection in early being pregnant and the beginning of seriously affected babies. notwithstanding, it used to be during the tragic occasions of 1962, whilst dramatic raises within the prevalence of phocomelia in infant babies in Germany, the uk, Japan, and different international locations have been traced to using the it sounds as if non-toxic sedative thalidomide by means of pregnant ladies, that toxicologists have been introduced nose to nose with the devastating hazard of chemically-induced developmental abnormalities. It were proven prior that chemotherapeutic brokers can cause harm to the constructing organism, however the absence of any recognized examples of drug-induced beginning defects had produced an air of complacency which used to be bolstered via the inability of any particular regulatory requisites for defense overview during this quarter. The value of the thalidomide tragedy, affecting a few ten thousand malformed childrens, was once enough to reason an instantaneous, and a few may say hasty, response via govt drug regulatory corporations in the course of the global to build a try out protocol which might observe capability teratogenic elements that will supply upward push to anatomical malformations.

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The suitability of limb-bud culture as a test of teratogenicity has been doubted (Wilson, 1978) since the development of the organ does not closely parallel development in vivo. , 1974a). While all the 50 The In Vitro Approach to Teratogenicity Testing cartilagenous rudiments of the forelimb do develop during culture, they are distorted compared with the normal organ in vivo (Aydelotte and Kochhar, 1972). , 1974a, 1976). Nevertheless, differentiation in vitro is consistent and reproducible and deviations due to treatment can be clearly detected.

A third approach is to culture embryos in serum prepared from animals pre-treated with the agent under testing. Recent studies of cadmium and cyclophosphamide embryotoxicity have demonstrated that this is a workable approach and have shown that a compound may exert differing effects when administered in this way, compared with direct addition to untreated serum (Klein et al.. 1980). A drawback of this approach is that the treated serum may vary from control serum, in addition to the presence of the agent and its metabolites.

These whole-animal in vivo tests have developed to a relatively standardised form and are utilised world-wide. They suffer, however, from two serious problems: they are expensive and time consuming to perform, and the extrapolation of the results to the human population is confounded by the well-known species variation in teratogenic response (Wilson, 1977). The number of compounds which must be tested for teratogenicity has increased dramatically with the continuous development of therapeutic, cosmetic and food-additive chemicals.

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Developmental Toxicology by Felix Beck (auth.), Keith Snell (eds.)

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