benzenedicarboxylic acid, or o-phthalates, which have the general chemical structure shown in Figure 1-1. Throughout this report, the term phthalates refers to the o-phthalates unless otherwise indicated.
The ester side chains can vary in length and structure. For example, they can be identical as in the case of di-n-butyl phthalate (R and R′ are both –CH2 CH2CH2CH3), or they can differ as in the case of butyl benzyl phthalate (R is –CH2CH2CH2CH3, and R′ is –CH2C6H5). The structural differences in the ester side chains give the phthalates their individual chemical and physical properties and alter their biologic activity. Table 1-1 lists common phthalates and selected metabolites. The abbreviations provided in Table 1-1 are used throughout this report.
Phthalates are used to impart flexibility to plastics and for their solvent properties. They are used in a wide variety of consumer products, including cosmetics, personal-care products, pharmaceuticals, medical devices, children’s toys, food packaging, and cleaning and building materials (Schettler 2006). The widespread use of phthalates has raised concerns regarding potential human exposure. As part of the 1999-2000 National Health and Nutrition Examination Survey (NHANES), the Centers for Disease Control and Prevention (CDC) measured several phthalate monoesters (metabolites of the diesters) in urine (Silva et al. 2004). Later surveys have provided additional data on phthalate exposure (CDC 2007a,b). Those and other surveys indicate widespread human exposure to various phthalates (Hauser and Calafat 2005).
Phthalate exposures can produce a variety of effects in laboratory animals; however, their adverse effects on the development of the reproductive system of male animals have led to particular concern. The effects of fetal exposure of male laboratory animals include infertility, decreased sperm count, cryptorchidism (undescended testes), hypospadias (malformation of the penis in which the urethra does not open at the tip of the organ), and other reproductive tract malformations and are similar to those that characterize the hypothesized testicular dysgenesis syndrome in humans (Skakkebæk et al. 2001). Currently, epidemiologic evidence of adverse human health effects of phthalate exposure is inadequate or limited (Hauser and Calafat 2005). Recently, the European Union