Advances in Biology Could Help in Assessing the Impact of Chemicals on Children.

Recent advances in developmental biology and genetics should help researchers develop methods for determining how a variety of chemicals can disrupt development in humans, according to a recent report from the National Research Council (NRC). Approximately half of all pregnancies in the United States result in prenatal or postnatal death or a less-than-healthy baby. Major developmental defects, such as neural tube and heart deformities, occur in approximately 120,000 of the four million infants born here each year. Exposure to toxic chemicals, both manufactured and natural, cause about three percent of developmental defects, and at least 25 percent may be the result of a combination of genetic and environmental factors.

"Many manufactured chemicals, as well as chemicals that occur in nature, have not been adequately evaluated for developmental toxicity," said Elaine Faustman, chair of the committee that wrote the report and professor of environmental health at the University of Washington, Seattle.

New approaches to developmental toxicology should incorporate simultaneous research on several fronts by experts from multiple scientific disciplines, the report says. It urges scientists to take advantage of new knowledge about the human genome when studying how genes and the environment interact to cause developmental defects. The report also calls for an intensified effort to expand the understanding of how even the smallest, simplest laboratory animals can serve as toxicological models for human biological systems.

In most animals--including the fruit fly, roundworm, zebra fish, and mouse--scientists recently have discovered how specific cells communicate with each other, ultimately activating proteins that turn particular genes on and off, thus regulating development. These "signaling pathways" are used repeatedly in various combinations at different times and locations in embryos and fetuses. Chemical disruption of the pathways could lead to abnormal development. Strikingly similar pathways are found in a wide range of animal species, including humans.

Relatively simple assessments on animal models could provide clues about which developmental pathways are most affected by specific chemicals, the committee said. On the basis of findings from these tests--or because of general concern about the prevalence of a chemical in the environment--more extensive studies could be conducted on animals whose biological systems more closely resemble those of humans.

In addition, the report says, the mapping of the human genome will increase understanding of gene function and expression and will help researchers identify unique alterations in genes, known as polymorphisms. Recent research has shown that individuals who have certain polymorphisms and who are also exposed to certain chemicals in utero have a higher occurrence of specific developmental defects than the general population. The committee emphasized that all stages of human development--from conception to puberty--should be examined in toxicity studies, since all developmental periods are potentially susceptible to toxic agents. In addition, there is a need to look at all adverse developmental outcomes, including growth retardation, behavioral effects, and death.

The vast amounts of data that could be generated by testing thousands of chemicals for potential developmental toxicity will require new databases capable of organizing this information in a way that is useful for risk assessment, the committee said. The databases should include information from industry, academic, and government research and should be linked with existing databases of developmental biology and genomics, as well as with those describing how drugs and chemicals are metabolized by the body. A separate relational database should be set up for chemicals that are found to interact with particular signaling pathways. This would help researchers study whether different chemicals that affect the same pathway are acting in a similar manner. In addition, educational programs and professional workshops should be organized to facilitate interaction among researchers in developmental toxicology, developmental biology, genomics, medical genetics, epidemiology, and biostatistics.