Phthalates
CATEGORY: Endocrine disruptor
USED IN: Plastics, cosmetics, fragrance in cosmetics and household cleaners
Phthalates are a group of endocrine-disrupting chemicals commonly used to render plastics soft and flexible. They are found in a wide variety of common products including plastics (e.g., children’s toys), cosmetics, pharmaceuticals, baby care products, building materials, modeling clay, automobiles, cleaning materials and insecticides. Phthalates are readily absorbed through the skin (Janjua, 2008) and can also enter the body through ingestion, inhalation or medical injection procedures (Schettler, 2005).
Phthalates have been found in indoor air and dust (Rudel, 2001) and in human urine and blood samples (Kato, 2003). National data collected by the CDC show that levels are highest in children ages 6 to 11 and in women, and that blacks have higher levels of phthalates than do whites (CDC, 2005). Phthalates have also been detected in human breast milk and urine (Hines, 2009; Meeker, 2009). Phthalates cross the human placenta, exposing fetuses to the hazards associated with exposure to an important class of EDCs during this critical period of development (Wittassek, 2009). Young infants are also exposed to high levels of phthalates, with measurable levels of seven different phthalates being found in infants born between 2000 and 2005 (Sathyanarayahna, 2008).
Phthalates are considered to be endocrine disruptors because of their complex effects on several hormonal systems including the estrogen and androgen hormone systems. Some phthalates, including butyl benzyl phthalate (BBP) and di-n-butyl phthalate (DBP), act as weak estrogens in cell culture systems. They can bind to estrogen receptors (ER), induce estrogen-appropriate cellular responses and act additively with estradiol in altering these systems (Jobling, 1995; Kang, 2005). Phthalates also bind weakly to the androgen receptor (AR), disrupting the cellular actions ordinarily initiated by the androgens (Borch, 2006). Those that bind most strongly to the AR, and therefore might be expected to exert the greatest effects through this pathway, include DBP, di-i-butyl phthalate (DiBP) and butyl benzyl phthalate (BBP) (Fang, 2003).
The endocrine-disrupting properties of this class of chemicals have been well established in the offspring of mother rats who had been treated with phthalates while pregnant. Phthalates have been shown to disrupt the development and functioning of male and female reproductive systems by interfering with the production of testosterone and estradiol, respectively (Jiang, 2007; Lovekamp-Swan, 2003). Abnormalities in male offspring exposed prenatally included nipple retention, shortened ano-genital distance and increased cryptorchidism (undescended testes) (Foster, 2005; Latini, 2006). Exposure of human mothers to phthalates, as measured by analysis of their urine samples, has also been associated with shortened ano-genital distances in their newborn sons—a measure of feminization of external genitalia (Swan, 2005).
A recent case-control study examined phthalate levels in apparently healthy girls who went through thelarche (breast development) before the age of 8, as compared with girls who underwent precocious puberty because of abnormalities in their neuroendocrine systems and with girls who were progressing through puberty at normal ages. Increased levels of monomethyl phthalate (MMP) were associated with early thelarche group, but not either of the comparison groups (Chou, 2009). Early breast development in otherwise healthy girls is associated with an increased risk for breast cancer (Steingraber, 2007).
Exposure of very young rats to BBP resulted in increased cellular proliferation in the terminal end buds of mammary tissue. BBP-induced changes in mammary cell gene expression profile were consistent with abnormalities in cellular differentiation and cell-cell communication (Moral, 2007).
In in vitro cell systems, BBP, DBP and another common phthalate, di-(2-ethylhexyl) phthalate (DEHP), significantly increase cell proliferation in MCF-7 breast cancer cells. In addition, these three phthalates inhibited the anti-tumor action of tamoxifen in MCF-7 breast cancer cells (Kim, 2004a). In another cell study, exposure of normal human breast epithelial cells to DBP resulted in changes in gene expression in pathways related to a number of systems, including immune responses, cell cycle regulation and antioxidant status of the cell (Gwinn, 2007).
