Content area
Full Text
Introduction
Phthalic acid diesters, commonly known as phthalates, are man-made chemicals used in a variety of industrial applications. High-molecular-weight phthalates (HMWPs), including di(2-ethylhexyl) phthalate (DEHP), are used primarily as plasticizers to increase the flexibility of vinyl plastic, which is used in many consumer products, such as pharmaceuticals, medical devices, and food packaging (Schettler 2006). Low-molecular-weight phthalates (LMWPs), on the other hand, including diethyl phthalate (DEP) and dibutyl phthalate, are used primarily as solvents in personal care products, such as cosmetics and shampoos (Meeker et al. 2009). Because phthalates are not covalently bound to the plastic matrix, they can leach out, resulting in environmental contamination and human exposure (Bosnir et al. 2003; Rudel et al. 2003; Schettler 2006).
In the body, phthalates rapidly hydrolyze to their corresponding phthalate metabolites (Silva et al. 2003). Metabolites are excreted unchanged or can be further metabolized or conjugated to increase water solubility and facilitate their urinary excretion (Silva et al. 2003). Quantification of phthalate metabolites in urine is the most common and reliable method for assessing phthalates exposure in epidemiological studies (Calafat et al. 2015). Several phthalate metabolites are readily detected in the urine of people in the United States (CDC 2017).
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). Population-based studies examining phthalates in relation to breast cancer (BC) incidence, a hormone-dependent cancer and thus potentially sensitive to environmental xenoestrogens (Brody and Rudel 2003), are limited. A study of Mexican women found positive associations between urinary concentrations of monoethyl phthalate (MEP) and mono(2-ethyl-5-carboxypentyl) phthalate (MECPP) and inverse associations between monobenzyl phthalate (MBzP) and mono(3-carboxypropyl) phthalate (MCPP) and BC risk (López-Carrillo et al....