Developmental effects, early

The disinfection of drinking water has been rightly hailed as a public health triumph of the twentieth century. Before its widespread use, millions of people died from waterborne diseases. Now, people in developed nations receive quality drinking water every day from their public water systems. However, chemical disinfection has also produced an unintended health hazard the potential for cancer and reproductive and developmental effects (including early-term miscarriages and birth defects) that are associated with chemical disinfection by-products (DBFs) [1-6]. Research is being conducted worldwide to solve these important human health issues. 

Figure 7 shows the effect of ectopic administration of T3 to the developing zebrafish embryo. At nontoxic concentration (50 nM), only a moderate fraction (less than 5%) of the zebrafish transcriptome shows significant changes. Ossification, visual processes, and the hematopoietic system were the physiological processes most affected by the treatment, in a pattern consistent with an advancement of the development in these particular functions (Fig. 7b). Genes involved in these three processes are known targets for TDCs during metamorphosis in amphibians, teleost fishes, and lampreys [54—60], and constitute molecular counterparts of different endpoints used to test for TDC in amphibians [56, 58]. Therefore, they are excellent candidates for markers of thyroid disruptors in zebrafish at early developmental stages. Chapter 14 provides a more in-deep description of the developmental effects of thyroid disruption in zebrafish embryos.

Developmental toxicity, defined in its widest sense to include any adverse effect on normal development either before or after birth, has become of increasing concern in recent years. Developmental toxicity can result from exposure of either parent prior to conception, from exposure of the embryo or fetus in utero or from exposure of the progeny after birth. Adverse developmental effects may be detected at any point in the life span of the organism. In addition to stmcmral abnormalities, examples of manifestations of developmental toxicity include fetal loss, altered growth, functional defects, latent onset of adult disease, early reproductive senescence, and shortened life span (WHO/IPCS 2001b). 

In the late 1950s the subtle and serious consequences of methyl mercury exposure became evident in Minamata, Japan. Initially, early signs of uncoordinated movement and numbness around the lips and extremities, followed by constriction in visual fields in fishermen and their families, baffled health experts. Developmental effects were clearly evident in infants who exhibited subtle to severe disabilities. This spectrum of adverse effects was finally related to methyl mercury exposure from consumption of contaminated fish. Minamata Bay was contaminated with mercury and methyl mercury from a factory manufacturing the chemical acetaldehyde. Mercury was used in the manufacturing process, which also resulted in both mercury and methyl mercury being discharged into Minamata Bay. The fish in the bay accu-... 

A.M. Cummings, M.T. Ebron McCoy, J.M. Rogers, B.D. Barbee, and S.T. Harris, Developmental effects of methyl benzimidazole carbamate following exposure during early pregnancy. Fundam. Appl. Toxicol. 18 288, 1992. 

In critical periods of development before they are born, and in the early months after birth, children and fetuses are particularly sensitive to the harmful effects of metallic mercury and methylmercury on the nervous system. Harmful developmental effects may occur when a pregnant woman is exposed to metallic mercury and some of the mercury is transferred into her developing child. Thus, women who are normally exposed to mercury vapors in the workplace (such as those working in thermometer/barometer or fluorescent light manufacturing or the chlor-alkali industry) should take measures to avoid mercury vapor exposures during pregnancy. Exposures to mercury vapors are relatively rare outside of the workplace, unless metallic mercury is present in the home. 

Developmental effects discussed in this section are restricted mainly to effects on fetal development, birth weight and weight gain in early life, and teratogenicity. Information regarding effects on the thyroid, immune system, and reproduction in offspring following perinatal exposure to PCBs is presented in Sections 3.2.3, 3.2.4, and 3.2.5, respectively. 

Perhaps the most striking illustration of the pervasive developmental effects of thyroid hormones is provided by children with severe thyroid hormone deficiency from early childhood, a condition termed cretinism. This may either be endemic in regions of severe iodine deficiency or sporadic due to failure of the thyroid to develop normally or defects in the synthesis of thyroid hormone. Affected children are dwarfed with short extremities, have mental retardation, and are inactive and listless. Other manifestations include facial puffiness, enlarged tongue, dry and doughy skin, slow heart rate, and decreased body temperature. Eor full recovery, treatment of patients with cretinism must be initiated before these florid features are apparent. Thus, pregnant women in areas of endemic cretinism due to iodine deficiency are supplemented with iodine and aU newborns are screened for thyroid hormone deficiency in many developed nations. 

Lead induces reproductive and developmental effects in laboratory rats after gestational or lactational exposure. Many of the effects occur in a concentration-dependent manner and have been observed at maternal BLLs that do not result in overt maternal toxicity (under 40 pg/dL). Animal studies have further demonstrated that effects of lead exposure during early development include impairment of retinal development and alterations in the developing hematopoietic and hepatic systems. Toxicology studies in male animals have reported de-... 

Although cross-sectional epidemiological studies, particularly those discussed earlier in this paper and elsewhere in this volume, provide important information on the health effects of environmental lead exposure, the emergence of prospective studies of lead s developmental effects has offered a notable advantage over the cross-sectional approach, namely a more precise characterization of the history of lead exposure during the period of development. The primary focus here is therefore on emerging prospective investigations of the relationship between lead and early development. 

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