Potential Risks of Phthalate Esters: Acquisition of Endocrine-disrupting Activity during Environmental and Metabolic Processing

Phthalate esters (PEs) are plasticizers used in many plastic products, food packaging materials, and medical bags. The widespread use of PEs has led to ubiquitous environmental contamination and human-exposure. Several epidemiological studies have indicated that exposure to PEs, especially during the prenatal period, induces adverse effects, including developmental and behavioral abnormalities, suggesting that PEs are endocrine-disrupters. Although the endocrine-disrupting effect of PEs is thought to be estrogen receptor (ER)-mediated, the ER-binding affinity of PEs is quite low, indicating that other mechanisms should be considered. In this review, we demonstrate that alkyl chain length and hydroxylation of PEs have a significant impact on binding to ERs and peroxisome proliferator-activated receptors. In addition, we discuss recent results from our laboratory that suggest additional risks may arise from environmental and metabolic processing of PEs through microbial transformation, microsomal metabolism, and sunlight exposure.