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Phthalates and Cumulative Risk Assessment: The Tasks Ahead
tures. Low-molecular-weight phthalates—including DMP, DEP, and DBP—are used in a variety of personal-hygiene and cosmetic products, such as nail polish to minimize chipping and fragrances as scent stabilizers (ATSDR 1995, 2001; NICNAC 2008). High-molecular-weight phthalates—including DEHP, DINP, and DOP—are used in plastic tubing, food packaging and processing materials, containers, vinyl toys, vinyl floor coverings, and building products (ATSDR 1997, 2002; ECB 2003; Kueseng et al. 2007). Medical supplies and devices may contain phthalates, as may some medications (for example, medications with enteric coatings) (Hauser et al. 2004). Table 2-1 lists some common phthalates and examples of their uses.
Phthalate exposures may occur through ingestion, inhalation, dermal absorption, and parenteral administration. The relative contributions of the exposures to the total body burden at various ages are not known.
BIOMARKERS OF EXPOSURE
Both animal and human studies demonstrate that exposure may occur throughout the life span, from the developing fetus through early infancy, childhood, and beyond. Phthalates can cross the placenta (Saillenfait et al. 1998; Fennell et al. 2004), have been measured in amniotic fluid in human studies (Silva et al. 2004), are present in breast milk (Parmar et al. 1985; Dostal et al. 1987), and can be measured in urine at all ages (CDC 2003, 2005; Sathyanarayana et al. 2008).
Human exposure to phthalates is assessed most frequently by measuring urinary polar metabolites. Urinary excretion of polar molecules is efficient, and their urinary concentration is generally 5-20 times that in lipid-rich body compartments. For example, the urinary concentrations of MEHP, MIBP, MEP, and MBP were 20-100 times those in blood or milk (Högberg et al. 2008). Recent advances in urinary phthalate biomarkers have led to the measurement of the oxidized metabolites; measuring these metabolites eliminates the potential problems of contamination inherent in measuring the parent compounds and their monoesters. The utility of other biologic matrices—such as blood, breast milk, and seminal plasma—for assessing human exposure remains largely unknown because there are few data. The incorporation of those novel matrices into human studies necessitates the measurement of oxidized metabolites to avoid problems with contamination by the ubiquitous parent diesters.
Exposure of the U.S. and German population to at least 10 phthalates has been demonstrated by measurement of their urinary metabolites as shown in Table 2-2. Other reports generally have found exposures similar to or consistent with those in Table 2-2 with respect to age, sex, and racial or ethnic variations. Except for MEP, urinary metabolites in U.S. children, males, Hispanics, and blacks are generally somewhat higher than those in adults shown in Table 2-2 (CDC 2005).