16 Effects and manifestations

A wide variety of responses characterizes developmental toxicity. Infertility, chromosomal and genetic disorders, spontaneous abortion, intrauterine death, prematurity, low birth weight, birth defects and functional disorders arc the effects of such drug interference with the developmental and reproductive processes. The manifestation of a developmental or reproductive toxicant can either be seen immediately after exposure, or will be expressed at a much later date. Interfering with male or female germ cell development might result in infertility, decreased sperm activity and/or libido, and impaired gamctogenesis. The effects on the pre-implantation stage will cause early embryonic death, extra-uterine implantation, or delayed transport of the fertilized zygote.

A critical phase for the induction of structural malformations usually occurs during the period of organogenesis. In humans, this critical period extends from about 20-70 days after the first day of the last menstruation period, or from 1 week before the missed menstruation until the woman is 44 days overdue. It may be unwise to rely absolutely on this time period. With physical agents such as X-rays used in laboratory animals, exposure can be limited exactly to a period of minutes to discover the exact sensitive period for inducing a specific disorder. However, with drugs and other chemicals, we are unsure about the time courses of absorption, metabolism and excretion. In addition, the actual proximate teratogen may be a metabolite rather than the compound administered. If the moment of final differentiation of a particular organ is known with certainty, then a teratogen must have been present prior to that lime, if it is presumed to be the causal agent of the malformation.

During the fetal period, the manifestations from toxicological interference arc growth restriction, some forms of structural malformations, fetal death, functional impairment, and transplacental carcinogenesis. The period of organ and system maturation extends beyond the period of organogenesis, and even beyond the prenatal period. Therefore, the susceptible period for the induction of insults that may lead to functional deficits is much longer than that for the induction of gross structural defects. Functions shown to be affected by pre- and early postnatal exposure to chemicals include behavior, reproduction, endocrine function, immune competence, xenobiotic metabolism, learning capacity, and various other physiological functions.

Fetal tissues are intrinsically highly vulnerable to carcinogens because of their high rate of cellular proliferation. This phenomenon has been demonstrated in rats, mice, hamsters, rabbits, pigs, dogs, and monkeys. About 25 compounds and groups of chemicals and 10 industrial processes have been shown to induce carcinogenic effects in human beings. However, there is convincing epidemiological evidence of transplacental tumor-induction in humans for only one compound - i.e. diethylstilbestrol (DES). Exposure to DES in utero leads to the development of clear-cell adenocarcinoma of the vagina or cervix in about 1 in 1000 of those at risk. Moreover, DES is now a recognized female genital tract teratogen. The effects of exposure to DES in utero for males arc known (e.g. short phallus); however, others (e.g. infertility) remain controversial.

Pregnancy Guide

Pregnancy Guide

A Beginner's Guide to Healthy Pregnancy. If you suspect, or know, that you are pregnant, we ho pe you have already visited your doctor. Presuming that you have confirmed your suspicions and that this is your first child, or that you wish to take better care of yourself d uring pregnancy than you did during your other pregnancies; you have come to the right place.

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