PRINCIPLES OF TOXICOLOGY - Biology East Borneo

224 REPRODUCTIVE TOXICOLOGYTABLE 11.2 Suspected Human Female Reproductive ToxicantsIndustrial/EnvironmentalArsenicCadmiumDiethylhexyl phthalateDioxinsIonizing radiationLeadMercuryPCBs—coplanar formsPharmaceutical Agents and DrugsAndrogens, estrogen, and progestinsBusulfanChlorambucilCyclophosphamideEthanolOpiatesVinblastinewhen there is a reproductive impairment. Also, the relatively small proliferative cell population in theovary and the intermittent nature of the proliferative stage makes the ovary less susceptible todisruptions of cell division. The compartmentalization of the active germ cell and its supporting follicleis also pertinent to ovarian toxicology since this means that only a few germ cells are vulnerable duringa given cycle. This decreases the likelihood that a toxic injury will cause permanent interference withoogenesis. While there are occasional toxicants, such as busulfan, that can wipe out the arrestedpopulation of primordial oocytes and prevent future follicular development, in general, the arrestedcells are fairly resistant to damage.Probably the most significant type of toxicants for female reproductive function are those thatinterfere with the dynamic endocrine balance required for folliculogenesis and ovulation. A wide arrayof toxicants have at least the potential to interfere with the female hormonal pattern, including heavymetals, drugs of abuse, and some chlorinated biphenyls. Chemicals that can structurally mimic thesteroid hormones, or have a competing functional activity, can be found among a variety of therapeuticdrugs, pesticides, and environmental contaminants. Though a mechanism for interfering with femalereproductive function is suggested, the impact of endocrinologically active chemicals, especiallythrough environmental exposures on human reproduction, is not yet clear.11.3 DEVELOPMENTAL TOXICOLOGYRecognition that environmental factors could cause congenital defects grew following the 1941 reportby Gregg that there was an association between exposure to Rubella virus (German measles) duringpregnancy and the occurrence of blindness and deafness in the offspring. Further analysis followinga Rubella epidemic and the thalidomide incident solidified people’s awareness of the potential forprenatal exposures to cause developmental defects. Part of the reason that recognition was so late incoming, even in the scientific community, is that the placenta was thought to serve as a barrierpreventing any potentially harmful agents from reaching the fetus. Since the 1960s it has become clearthat the placenta is actually quite porous to chemicals of the molecular size that encompasses all butthe largest drugs and industrial compounds. Developmental toxicity testing has now become commonplace,and many agents that can affect development, chemical and biological, as well as physicalphenomena, have been identified.As we have seen in male and female reproductive toxicology, experimental demonstrations of toxicpotential far outnumber demonstrated cases of human developmental toxicants. This may be due inpart to species differences and the high doses used in experimental protocols; however, with developmentaldefects, it is also not always clear whether the experimentally demonstrable differences instructure or behavior can be extrapolated to humans and considered abnormal. Overall, the class ofchemicals with demonstrated human effects are less important in the population than both biologicallyinfective agents, such as Rubella virus, syphilis and cytomegalovirus, and maternal metabolic disor-