Endocrine disrupting chemicals (EDCs) provoke unusually challenging questions. They confound us because, rather than poisoning us overtly, as by killing cells, they distort the body's intrinsic hormonal mechanisms. They can displace, mimic, antagonize, or even amplify the vital processes governed by hormones, producing an array of subtle aberrations that are difficult to grasp if we seek answers by traditional methods.
The 27th International Neurotoxicology Conference addressed a variety of neurobehavioral outcomes associated with exposure to EDCs. One crucial element of this equation, however, was implicitly ignored in these presentations: exposure sources. The current report explores this question. It shows that individual behavioral choices and community lifestyle practices determine the sources of two important EDCs. Although it might be argued that the approach described here is more anthropological than toxicological, we view it instead as a means to help close a major gap in our comprehension of how exposure and consequences are intertwined.
EDCs are found in many chemical classes, including pharmaceuticals, pesticides, dioxins, PCBs, organic tin compounds, brominated flame retardants, perfluorinated coatings for cook-ware, and others. In this report, we focus on two EDCs that have provoked intense concern about their neurotoxic properties and a corresponding volume of research.
One, bisphenol A (BPA), is a single chemical. The other, phthalate esters, represents a large chemical class. Both agents are produced in massive amounts, are used extensively in plastics manufacture, and are widely distributed in the environment and in human tissues (Koch and Calafat, 2009
). In laboratory studies, BPA and phthalates are shown to produce adverse effects on a variety of organ systems, although the exposure levels at which they do so is debated. Like other EDCs, they seem to exert their most potent and permanent effects on the developing organism. Although both BPA and phthalates are assumed to be metabolized rapidly, there is also evidence that, because they are fat-soluble, some portion accumulates in fatty tissues from which they are slowly released (Stahlhut et al., 2009
, for BPA; Frederiksen et al., 2007
, for phthalates).
BPA is employed in the manufacture of polycarbonate plastics such as the epoxy resins found in can linings, and in thermal paper products, dental sealants, baby bottles, food containers, and other plastic products. The Centers for Disease Control and Prevention (CDC) reports that 93% of Americans aged 6–85+ show detectable levels of BPA metabolites in urine (Calafat et al., 2008
) and an expanding literature demonstrates the presence of the parent compound and metabolites as well in various human tissues, blood, and even in newborns and breast milk (Vandenberg et al., 2010
Foods and beverages are major exposure sources (Koch and Calafat, 2009
; Wilson et al., 2007
). Because residual BPA typically leaches from the can or container, stored food or beverage can become contaminated (vom Saal and Hughes, 2005
). Carwile et al. (2011)
found that a daily serving of canned soup for five days raised BPA levels in urine by 1200%. But BPA is also found in plastic cups, recycled cardboard (e.g., pizza boxes) and paper. The analysis by Lakind and Naiman (2011)
, based on data from the 2005–2006 NHANES, found that soft drinks, meals outside the home, and – a special cause for concern – school lunches, were associated with higher urinary BPA values.
BPA in thermal paper such as store receipts, and in personal care products, can penetrate the dermis (Biedermann et al., 2010
), raising the possibility that it then bypasses liver metabolism and enters the bloodstream directly. Inhalation of dust particles containing BPA is another potential exposure source (Geens et al., 2009
As with other EDCs, early development is the phase of the life cycle that appears most sensitive to BPA exposure. In rodents, numerous toxic effects are seen in a variety of tissues and organ systems. Among the most prominent developmental effects are those affecting the brain and behavior. Earlier reviews by Vandenberg et al. (2009)
and vom Saal et al. (2007)
noted the wide scope of BPA neurotoxicity. Rubin (2011)
, Kundakovic and Champagne (2011)
and Wolstenholme et al. (2011)
have addressed associated domains such as epigenetics and obesity. Because BPA research is such an active area, we can expect to see a substantial volume of new data in the next few years. For example, Braun et al. (2009
) reported a correlation between prenatal exposure levels and externalizing behavior (increased hyperactivity and aggression) in girls two years of age and poor emotional control and anxiety and depression at three years of age.
As with BPA, humans are exposed to phthalates by many routes: orally, dermally, through inhalation and even subdermally, the route varying with the particular phthalate. For example, exposure to diethylhexyl phthalate (DEHP), the only phthalate regulated in drinking water, occurs primarily through food and beverage consumption. It is also an important component of polyvinyl chloride (PVC), and soft plastics that find their way into children's mouths as from toys. It can enter the circulation dermally (as in personal care products), internally (as in medical tubing), and inhalation in the form of dust particles from sources such as vinyl flooring and upholstery (Afshari et al., 2004
; Bornehag et al., 2005
; Jaakkola and Knight, 2008
). DEP is a component of many cosmetics we apply to the skin, including lotions for babies, shampoos, and aftershave products. DBP can be found in products that we inhale, such as hair spray and nail polish. BBzP can also be found in vinyl floor tiles and some cosmetics.
A large rodent literature testifies to the ability of several phthalates to interfere with the development of the male reproductive system (e.g., Foster, 2006
). These phthalates produce a cluster of abnormalities in newborn males, stemming from prenatal exposure, labeled as the Phthalate Syndrome
. The abnormalities are seen in reproductive tract structures, the external genitalia (in the form of hypospadias), as cryptorchidism, and as testicular pathology. In addition, phthalates reduce anogenital distance (AGD) in males, which, in both rodents and humans, is greater (50–100%) in males than in females. These changes result from a reduction in testicular testosterone production during a critical developmental period. A remarkably similar syndrome occurs in humans and has earned the term, Testicular Dysgenesis Syndrome
(Skakkebaek et al., 2003
; Sharpe and Skakkebaek, 2008
; Wohlfahrt-Veje et al., 2009
Because the bulk of the rodent literature had been based on exposure levels far greater than those experienced by humans, phthalates had not, until recently, been viewed as threats to human health. That perception was overthrown by a publication (Swan et al., 2005
) indicating that AGD in boys was inversely related to urinary concentrations of phthalate metabolites during pregnancy. It has led to a surge in publications supporting and expanding the original observations (Swan, 2008
; Meeker et al., 2009
; Hauser et al., 2006
Nonreproductive behaviors are another target of phthalates. Swan et al. (2010)
measured play behavior in young children with a questionnaire, completed by the parents, whose items asked about behaviors such as toy preferences (e.g., trucks vs. dolls). Higher concentrations of phthalate metabolites during pregnancy reduced masculine play behavior in boys.
Other nonreproductive behaviors affected by phthalates include cognitive function (Engel et al., 2010
; Kim et al., 2009
; Cho et al., 2010
; Whyatt et al., 2012
), and social responsiveness (Miodovnik et al., 2011
). Asthma and allergy in children (Bornehag and Nanberg, 2010
) are also associated with phthalate exposure as measured by phthalates in household dust. And, as with BPA, phthalate exposures are associated with obesity (Hatch et al., 2010
; Stahlhut et al., 2007
), male fertility (Hauser, 2008
), and heart disease (Lind and Lind, 2011