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Human Health: Neurological Development Effects

EPA scientists are researching how endocrine disrupting chemicals affect the brain and nervous system

Issue

Endocrine disrupting chemicals can affect multiple systems in the body, including the brain and nervous system. One way chemicals can affect the brain is through disrupting the levels of thyroid hormones - one of the main hormone systems that interests EPA's Endocrine Disruptor Screening Program. These hormones help control the development and maturation of the central nervous system. In humans, even modest reductions in circulating thyroid hormones during pregnancy can have adverse effects in children - such as reduced IQ, deficits in learning ability, and delays in learning to speak (Lazarus, 2012). Studies using animal models support these findings. For instance, EPA scientists have found reductions in thyroid hormones in rats exposed in utero to ammonium perchlorate, a component of rocket fuel and an environmental contaminant. These rats also had permanent changes in brain function, showing defects in neuronal firing in areas of the brain involved in learning - even at doses that resulted in only modest reductions in thyroid hormones, when measured weeks after birth. Biomonitoring studies in humans indicate a relationship between perchlorate exposure at levels commonly found in the environment and thyroid hormone levels in blood (Blount et al., 2006). However, the quantitative relationship between reductions in thyroid hormones and neurological effects has yet to be precisely defined. EPA scientists are currently researching the degree to which thyroid hormones must be reduced before neurological effects begin to emerge, the timing and duration over which exposure must occur to induce them, and the most sensitive endpoints for detection of the insult, among other outstanding questions.

Action

EPA scientists are evaluating the neurological effects of perturbing thyroid hormones at a range of doses and at different stages of development. For these studies, they are using precise means to perturb thyroid function, for instance giving rats chemicals that specifically interfere with the synthesis of thyroid hormone. With these tools the scientists are determining the degree of hormone reduction that will impact brain function.

EPA scientists are also evaluating the thyroid disrupting properties of other chemicals in addition to perchlorate, such as triclosan, a common ingredient in hand soaps and other consumer products that could affect thyroid hormones. Scientists are exploring new methods to develop rapid, automated chemical tests (called high throughput in vitro or test tube assays) that can be used to screen chemicals for potential thyroid disruption, defining sensitive neurological outcome measures for low level hormone disruption, and developing biologically based dose-response models that will facilitate extrapolation of thyroid effects observed in animals to humans.

Results and Impact

EPA scientists have evaluated the neurological effects of modest reductions in thyroid hormones. They have found neuronal effects in offspring of pregnant rats who experienced reductions in serum hormone of less than 25 percent. Scientists have also identified new methods to assess effects on the nervous system, which could reduce the reliance on behavioral assessments of neuro development. These new methods include imaging techniques to determine the effects on white matter content in brain, identifying subtle abnormalities in brain structure, and examining the disruption of thyroid-sensitive genes in brain tissue. Measurements generated from these methods may be more readily translated into computational models that can be used to make predictions about the neurological effects of chemicals. Such models will help scientists in the Endocrine Disruptor Screening Program to streamline their assessment of chemicals that may have an effect on the nervous system. For instance, the resulting research will help EPA prioritize which chemicals need animal testing and which tests are most appropriate for different types of chemicals. The in vitro assays in development and animal research are complementary, each informing the other. The result will be a strong biological foundation upon which to base both quantitative biological and computational models that will better predict the potential for chemicals to impact neurological development.

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