The effects of Di(2-Ethylhexyl) phthalate exposure on brain development

Phthalates are synthetic chemicals used primarily to increase the flexibility and the durability of plastic products, such as food storage containers, children's toys, and personal care products. Given the widespread use of these products, it is likely that exposure to phthalates is unavoidable in our daily lives. There has been increasing concern over the dangers of exposure to these compounds, especially in developing organisms as key organ systems, such as the brain, are undergoing rapid development at this time. Phthalates have anti-androgenic properties, meaning these chemicals interfere with the biological role of androgens (i.e., hormones critical for the masculinization of the brain) as well as suppress enzyme activity, mRNA expression, and protein levels important for brain masculinization and steroid synthesis. Interfering with androgens may directly or indirectly alter or prevent brain masculinization resulting in a more feminized version of the brain. A recent study has shown that phthalate exposure also affects estrogen synthesis in both males and females in addition to interfering with normal steroid homeostasis. Research investigating the effects of phthalates on brain development is limited. In a recent study, male rats were more vulnerable to the effects of phthalate exposure during development showing obvious structural deficits in the hippocampus (important for learning and memory), whereas brains of phthalate-exposed females were similar to control females. Researchers have also linked phthalate exposure to alterations in the dopaminergic pathway (important for movement and reward). The mechanisms of action underlying phthalate-induced changes in neurodevelopment have not been fully elucidated; however, it is likely that altered steroidogenesis may play a vital role. While research on neurodevelopmental effects of phthalate exposure is increasing, information is incomplete on the underlying neural and molecular mechanisms of phthalate toxicity in the brain. We recommend more extensive animal studies on phthalate exposure during vulnerable developmental periods when rapid structural and functional changes in the brain are taking place. Animal models will be crucial in establishing a causal link between phthalate exposure and changes in neuro-circuitry and in understanding the neural and molecular mechanisms which contribute to phthalate-induced changes in the developing brain