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

Abstract

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.

Effects and Mechanisms of Phthalates’ Action on Reproductive Processes and Reproductive Health: A Literature Review

“…Therefore, the phthalates can bind to the receptors as the agonists or antagonists. It depends on the size of the side chain [ 220 ].…”

Partition and Fate of Phthalate Acid Esters (PAEs) in a Full-Scale Horizontal Subsurface Flow Constructed Wetland Treating Polluted River Water

“…Phthalate acid esters (PAEs) and phthalates are synthetic compounds used mainly as plasticizers to improve the flexibility, durability, and transparency of plastics [1]. As additives in numerous products, including coatings, coverings, insecticides, flooring, drainpipes, packaging, cosmetics, adhesives, and paints [2], they may migrate into the environment via various pathways including microbial transformation, microsomal metabolism, and sunlight exposure [3]. With strong chemical bond to the matrices of polymers, PAEs are persistent and found in almost all the environments, such as rivers [4], sediments [5], soils [6], sewage [7], air [8], biota [9], and even in human tissue [10].…”

Urinary Phthalate Metabolite Concentrations and Breast Cancer Incidence and Survival following Breast Cancer: The Long Island Breast Cancer Study Project

“…Despite their relatively short biological half-lives, which range from hours to days ( Koch et al 2006 ), phthalates are hypothesized to have a wide range of adverse health effects due to their potential as endocrine-disrupting chemicals, acting as hormone agonists and antagonists ( Okamoto et al 2011 ) and as possible carcinogens ( ATSDR 2002 ). Phthalate exposure has been associated with reproductive and developmental outcomes in both animals and humans ( Meeker et al 2009 ) and with hepatic tumors in F344 rats and B6C3F1 mice chronically administered DEHP, with the lowest-observed-effect level of DEHP carcinogenicity in the rat reported at 0.6% of percentage in feed, and the no-observed-effect level reported at 0.1% of percentage in feed ( Ito and Nakajima 2008 ).…”