exposures at other periods could affect juvenile, adolescent, and adult development, and might affect gametes and reproductive organs in ways that are only expressed much later in the period of pregnancy.

TOXICANT EXPOSURE AND DEVELOPMENTAL DEFECTS

The current understanding of the various causes of developmental defects is incomplete. A crude distinction can be made between intrinsic and extrinsic causes. Intrinsic causes include genetic defects (mutations), endogenous chromosomal imbalances (e.g., meiotic nondisjunctions), endogenous metabolism (e.g., phenylketonurea), and perhaps failures in the complex developmental processes themselves. Extrinsic causes include the enormous variety of environmental inputs such as infection, nutritional deficiencies and excesses, life-style factors (e.g., alcohol), and closer to the concerns of this committee, the myriad agents—pharmaceuticals, synthetic chemicals, solvents, pesticides, fungicides, herbicides, cosmetics, food additives, natural plant and animal toxins and products, and other environmental chemicals—encountered by humans. Other environmental factors, such as hyperthermia, ultraviolet irradiation, and X-rays, should be included. As noted before, developmental defects comprise all structural and functional deficits detected in the implanted embryo, fetus, neonate, infant, or child.

The committee was asked to consider environmental agents that might cause developmental defects. Such agents include mercury, lead, and polychlorinated biphenyls. Natural plant and animal products and toxins have long been recognized as agents that can cause toxicity. They were some of the first environmental agents to be identified as teratogens. Agents can enter the environment by either deliberate (e.g., pesticide residues on food) or accidental (e.g., chemical spills) releases, and humans can be exposed through food, drinking water, or air. Pharmaceuticals and food additives generally would not be considered environmental agents; however, many of the issues under consideration for environmental agents can also apply to these agents. Additionally, it is possible that they incidentally enter the environment at significant concentrations and become environmental agents.

What fraction of developmental defects can be attributed to extrinisic or intrinsic causes? Wilson (1973) estimated that 25% of congenital anomalies in humans are attributable to genetic causes. Then, the author estimated that 65-75% of developmental defects are of unknown causation and attributed fewer than 10% of the anomalies to known environmental causes, including maternal diseases (e.g., diabetes and hypertension), infectious agents (e.g., rubella and syphilis), and mechanical problems (e.g., uterine deformations). Approximately 1% are known to be due to environmental toxicant exposures, including ionizing radiation and hyperthermia (Wilson 1973).



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