Lindsay McCormick is a Research Analyst.
Phthalates are chemical plasticizers found in a wide array of industrial and consumer products, including polyvinyl chloride (PVC) piping and tubing, cosmetics, medical devices, plastic toys, and food contact materials. Because phthalates are often not strongly chemically bound to these products, they can leach out of those products and into the environment around us. Given this, it may not be surprising that phthalates and their metabolites can be measured in the bodies of nearly all people tested.
This post reports on important new research on DEHP and summarizes the state of regulation of the chemical in the U.S. and abroad.
Evidence from laboratory experiments where animals are dosed with phthalates strongly suggests that these chemicals have adverse effects on the male reproductive system. The National Research Council (NRC) concluded in its 2008 report that male rats prenatally exposed to certain phthalates during a critical developmental window of sexual differentiation are prone to a number of reproductive tract abnormalities; further, the NRC concluded that it is “biologically plausible” that similar effects may occur in humans exposed to certain phthalates in the womb.
Now, a study conducted by Swan et al. and published in February in the journal of Human Reproduction corroborates this hypothesis of effects in humans for one phthalate: diethylhexyl phthalate (DEHP).
In this study, the largest of its kind, researchers recruited pregnant women from prenatal clinics in San Francisco, Minneapolis, Rochester (NY), and Seattle and measured phthalate levels excreted in the urine during the first trimester of pregnancy. To assess the potential impact on reproductive health, the researchers measured anogenital distance (AGD) – the distance between the anus and the genitals – in the infants immediately after birth. AGD is an indicator of prenatal exposure to androgen (a male sex hormone), with typical AGDs being 50-100% longer in males than in females. Shorter AGD is a well-established marker for disruption of male genital tract development (or “feminization”), and has been associated with reduced fertility in males.
This study found that AGD was significantly shorter in male infants whose mothers were more highly exposed to DEHP during their first trimester of pregnancy. No association between prenatal exposure to phthalates and AGD was found in female infants.
A well-designed study
The Swan et al. study is not the first to suggest that prenatal phthalate exposure in males may impact their ability to reproduce as adults, as measured by AGD (for example, see here and here). However, it arguably provides the most robust evidence to date of such effects in humans. According to the authors, this study is “far more powerful and precise” than any other study that has previously investigated this question. Some of the strengths of this study include:
- A large sample size: The study reported results on 753 participants (366 boys) – more than all other studies published on this topic combined.
- Well-timed exposure measurement: Urine samples were collected during a critical window of genital development, allowing the researchers to measure phthalate levels during the most relevant timeframe during pregnancy.
- Precise genital measurements at birth: All measurements were taken using standardized equipment and rigorous protocols, and were timed within a short window after delivery to minimize variability.
DEHP and female reproductive health
Although much less studied, preliminary research suggests that DEHP may also affect the female reproductive system. A new study published by researchers at University of Illinois in April found that, relative to an unexposed control group, female mice dosed with DEHP during pregnancy gave birth to more male offspring, took longer to get pregnant, and showed altered ovarian structure. Several other studies demonstrate a potential for DEHP to adversely impact the female reproductive system; however, this area warrants further research.
With this mounting evidence of health concerns, what is the state of regulation of DEHP?
Regulation of DEHP in the U.S.
DEHP is regulated by a number of federal and state entities in the U.S. (see tables below). Research demonstrates that DEHP exposure has significantly decreased in the U.S. since the early 2000s, which may be largely attributed to the substitution of DEHP with other compounds (including other phthalates) because of regulatory pressure and public concern. Despite this trend, the Swan et al. study suggests that current levels of DEHP exposure may still be sufficient to remain detrimental to male reproductive health.
With the exception of a national ban in some children’s products (see our previous blog) and a few limits in food contact materials imposed by the Food and Drug Administration (FDA), there has been relatively little regulation of DEHP in consumer products at the federal level. According to a report published in August 2014 by the Chronic Hazard Advisory Panel (CHAP) on Phthalates, a group of experts convened by the U.S. Consumer Product Safety commission (CPSC), the largest source of exposure to DEHP in pregnant women is diet. DEHP is lipophilic (“fat-loving”) and can leach from food packaging and other food contact materials (e.g., equipment used in mechanical milk processing) into fatty foods such as dairy and meats.
Although there are some limits on DEHP use in food contact materials, there is no restriction on the amount that can be leached into the food itself (i.e., “migration limit”). In order to reduce dietary exposure in women of reproductive age, further regulation in food contact materials and establishment of a DEHP migration limit may well be necessary.
|Examples of U.S. Federal Regulation of DEHP|
|Federal Agency||Regulated Product/Media1||Statute||Description|
|Consumer Product Safety Commission||Children’s products/toys||Consumer Product Safety Improvement Act||Banned from children’s toys and certain child care articles in any amount greater than 0.1%|
|Environmental Protection Agency||Air||Clean Air Act||Listed as a hazardous air pollutant (HAP)|
|Environmental Protection Agency||Water||Safe Drinking Water Act||Limited to 6 ppb in drinking water|
|Food and Drug Administration2||Food contact materials||Federal Food, Drug and Cosmetic Act||Limited in its use in a number of food contact surfaces|
|Food and Drug Administration||Bottled water||Federal Food, Drug and Cosmetic Act||Regulated in bottled water to level set by EPA|
|Occupational Safety and Health Administration||Workplace air||Occupational Safety and Health Act||Permissible exposure limited to 5 mg/m3 of air over 8 hours|
1 Also see FDA’s guidance (non-regulatory) on use of DEHP in prescription and non-prescription drug products. This does not apply to drug delivery systems, packaging, or medical equipment.
2 See table 8-1 in this ATSDR document and the FDA List of Indirect Additives Used in Food Contact Substances
A number of states have implemented DEHP restrictions in water and air at levels differing from the national standards, and a few states – California, Vermont, and Washington – have banned DEHP in toys and childcare products. Washington’s “Children’s Safe Products Act” extends restrictions to DEHP in cosmetics marketed to children (under 12 years). In addition to DEHP restrictions, three states have required reporting or disclosure of DEHP use in products (see table below).
Examples of State Reporting or Disclosure Requirements for DEHP
|California||Proposition 65||DEHP is listed as carcinogenic and a male reproductive toxicant under Prop 65. Products containing DEHP in California must exhibit a warning to consumers.|
|Washington||Chemicals of High Concern to Children||Manufacturers are required to report use of DEHP in a product (amount present and function in the product) to the state.|
|Minnesota||Priority Chemicals||No current reporting requirement. Options for regulating/reducing use of Priority Chemicals in consumer products are being considered.|
Regulation of DEHP abroad
Many other countries, including Canada, Australia, and Turkey have taken regulatory action to restrict DEHP. However, the European Union (EU) has adopted the most aggressive restrictions. In the mid-2000s, the EU banned DEHP from children’s products and cosmetics and restricted its use in some food contact materials (including a migration limit of 1.5 mg/kg food). In 2008, DEHP was added to the “candidate list” of “Substances of Very High Concern” under the EU’s chemical safety law (REACH), thereby requiring suppliers of any article containing DEHP above a threshold to inform members of its supply chain of the use of DEHP. Most uses of DEHP were banned (or “sunsetted”) in the EU as of February 21, 2015, with the exception of three manufacturers who were granted use authorizations for specific uses (for more information on authorization of DEHP under REACH, see our previous blog). However, uses that do not fall under REACH, such as food packaging, were unaffected by this ban.