Why is exposure to phthalates relevant to health?
Phthalates are common agents used to hold color or scent in products such as paints and perfumes, to maintain gloss or shine as in paints, or to impart flexibility to plastics. They are high production volume chemicals used mainly as plasticizers.
Because of their ubiquitous presence, phthalate exposure is quite common. Routes of exposure for smaller molecular weight phthalates are thought to be primarily inhalation and dermal, whereas larger phthalates tend to be ingested. Contact with certain medical equipment such as plastic tubing may also lead to phthalate exposures.
Parent phthalate diesters are rapidly metabolized to monoester forms, which are then oxidized or reduced to increase their elimination through the urine. Phthalate metabolites are considered to be endocrine disrupting (modulating) chemicals with anti-androgenic effects and are potential carcinogens. Prenatal exposure to phthalates has been linked to neurocognitive deficits in children and decreased anogenital distance in males. Phthalate exposure has also been linked to changes in reproductive function in men. Other effects such as alterations in pubertal timing are still being investigated.
What types of questions can be answered?
Exposure to phthalates can be estimated by measuring their monoester and oxidative metabolites in urine and other specialized matrices; parent phthalate diesters have been measured in environmental samples. Many published data exist with which to compare these exposures including general U.S. population data published in Centers for Disease Control and Prevention’s (CDC) National Report on Human Exposure to Environmental Chemicals.
Levels of phthalate metabolites reflect exposure over the last few days, but several longitudinal studies have suggested a strong inter-correlation of phthalate metabolites in multiple samples taken over time. To relate phthalate metabolites to a chronic condition, multiple samples or studies to indicate within-person variability over time may be necessary.
How can phthalate exposure be measured?
- Analytes: Primary (monoester) and secondary (oxidative and elimination products) metabolites of phthalates are measured in urine to evaluate exposure. The most common parent phthalates whose metabolites are measured include 2-diethylhexyl phthalate, diethyl phthalate, dibutyl phthalate, diisononyl phthalate, diisodecyl phthalate, and benzylbutyl phthalate, although others are also measured. In particular, new phthalates have been used to replace some of the listed diesters, and metabolites of those compounds are also being analyzed in HHEAR.
- Methods: Almost all methods couple liquid chromatography with mass spectrometry detection. The use of isotopically labeled standards provides a robust way to quantify measurements.
- Types of biospecimens: Urine is the primary matrix of choice used for measurement. Blood-based samples are typically not suitable because of contamination with parent phthalates and subsequent conversion in vivo or in vitro to monoesters by residual blood esterase activity. Levels in blood are also much lower than in urine, further complicating measurement and accuracy. Other matrices include amniotic fluid, meconium, and breast milk, but these may also be subject to contamination issues, especially breast milk collected via pumping and meconium collected from diapers.
- Types of environmental samples: House dust and silicone wristbands are the most common media analyzed, but other media (such as air samplers and soil) have also been used.
How does HHEAR ensure the quality of its analyses?
Because parent phthalate diesters are nearly ubiquitous in the environment, analytical procedures focus heavily on evaluation of external contamination in both sample collection and analysis. If possible, the inclusion of field “blanks” in a study can help identify any contamination from collection/storage sources. Phthalate-free tubes, vials, and other materials must be used during collection. For breast milk, samples should be collected by manual expression. Positive and negative controls are included in each analytic run because background contamination can be problematic.
What sample quality and quantity are necessary?
Typically 0.1-1.0 mL of urine or one gram of dust are used. Smaller volumes can be used but usually translate to lower frequency of detection. Samples must have not undergone repeated freeze-thaw cycles and must have been collected to minimize phthalate contamination.
Centers for Disease Control and Prevention. National Biomonitoring Program Factsheet: Phthalates.
Environmental Protection Agency. America's children and the environment. Biomonitoring: phthalates.
Braun JM, Sathyanarayana S, Hauser R. Phthalate exposure and children’s health. Current Opinion in Pediatrics. 2013;25(2):247-254.
Guo Y, Kannan K. Challenges encountered in the analysis of phthalate esters in foodstuffs and other biological matrices. Analytical and Bioanalytical Chemistry. 2012;404:2539-2554.