Health effects associated with phthalate activity on nuclear receptors

Phthalates are endocrine disruptors, widely used as plasticizers to impart flexibility in plastics, and as solvents in personal care products. Due to their nearly ubiquitous use in consumer products, most humans are exposed to phthalates daily. There has been extensive research on the reproductive health effects associated with phthalate exposure, but less attention has been paid to other actions. This review aims to summarize the known action of phthalates on different nuclear receptors. Some phthalates bind to and activate the estrogen receptor, making them weakly estrogenic. However, other phthalates antagonize androgen receptors. Some high molecular weight phthalates antagonize thyroid receptors, affecting metabolism. Several phthalates activate and interfere with the normal function of different peroxisome proliferator-activated receptors (PPARs), receptors that have critical roles in lipid metabolism and energy homeostasis. Some phthalates activate the aryl hydrocarbon receptor, which is critical for xenobiotic metabolism. Although phthalates have a short half-life in vivo, because people are continuously exposed, studies should examine the health effects of phthalates associated with long-term exposure. There is limited research on the effects of phthalates on health outcomes aside from reproductive function, particularly concerning are childhood adiposity, behavior, and learning. There is also limited information on actions of phthalates not mediated via nuclear receptors. Humans are exposed to multiple chemicals simultaneously, and how chemical mixtures act on nuclear receptor activity needs study. Although we know a great deal about phthalates, there is still much that remains uncertain. Future studies need to further examine their other potential health effects.