Phthalates: Friends or Foes?

Author: Su Jingran

 

Figure 1. Children’s rubber duck containing phthalates. The flexible plastic feel of the rubber duck may be the result of using phthalates in the manufacturing process.

Phthalates: The Everywhere Chemical

Ladies put a variety of cosmetics on their faces for beauty. People use soaps and shampoos every day to clean their bodies. Children crawl around the furniture and touch many things, finally putting their hands in their mouths or biting the cute toys. Plastic is even everywhere; disposable plastic bags in supermarkets, food packaging boxes, and even thermos cups at our hands, may all be contributed by phthalates, a magic chemical. Despite the wide usages phthalates have, recently a tidal wave of new research has documented their wide-ranging negative health impacts. Then it is natural to ask: is phthalate a friend or foe?

What is phthalate?

The diesters of 1,2-benzenedicarboxylic acid (phthalic acid), commonly known as phthalates, are a group of man-made chemicals[1]. One important chemical property of phthalates is that they are esters, which means they are formed from the reaction of an alcohol with an organic acid. Phthalates are colorless, odorless, and have low volatility, making them useful in a variety of applications. They are commonly used as plasticizers because they have a low vapor pressure and are able to mix well with a wide range of materials, improving their flexibility and durability. Moreover, phthalates are used as solvents, and additives in a variety of consumer products, including food packaging, personal care products, medical devices and toys.

However, as the phthalate plasticizers are not chemically bound to PVC plastics, they can leach, migrate or evaporate into indoor air and atmosphere, foodstuff, other materials, etc. [2] They are also known to be hydrophobic, meaning they do not dissolve easily in water, which can lead to their accumulation in the environment and potential exposure to humans and wildlife. Additionally, phthalates are susceptible to degradation under certain conditions, such as high temperatures, sunlight, and exposure to certain chemicals, which can release them into the environment and pose a risk to human health.

CDC’s warning on phthalates

In 2003, researchers at the US Center for Disease Control (CDC) documented widespread exposure to a high level of phthalates across the general American public and recommended that the chemicals and their effect on human health be studied further.[3] They measured 13 phthalate metabolites in the urine of 2,636 or more people aged 6 years and older who took part in the National Health and Nutrition Examination Survey (NHANES) during 2003–2004. Then they published the findings in the Fourth National Report on Human Exposure to Environmental Chemicals.

The CDC’s recommendation helped unlock funding for dozens of studies focused on phthalates, resulting in a tidal wave of recently published reports that largely indicate the CDC’s concern was warranted. Its warning on phthalates also caught the attention of senators Barbara Boxer and former US representative Henry Waxman, who included the class of chemicals in their Consumer Product Safety bill, passed in 2008. That bill banned the use of some phthalates in children’s products, passed an interim ban on others, and required that the Consumer Product Safety Commission take a close look at the chemicals. [3]

Exposure and metabolism to human body

Traditionally, ingestion has been considered an important route of exposure for phthalates. Although phthalates have low volatility, they off-gas and are present in residential indoor air. Dermal contact and parenteral exposure from medical devices containing phthalates may also contribute to exposure.[2] On exposure, phthalates are rapidly metabolized and excreted in urine and feces.

Figure 2. Selected metabolites of di(2-ethylhexyl) phthalate (DEHP) in humans: mono(2-ethylhexyl) phthalate (MEHP), mono(2-ethyl-5-hydroxyhexyl) phthalate (MEHHP), mono(2-ethyl-5-oxohexyl) phthalate (MEOHP), and mono(2-ethyl-5-carboxypentyl) phthalate (MECPP).

The exact metabolic pathway of phthalates depends on the specific phthalate compound and the individual’s metabolic capacity. Some phthalates (see Figure 2.), such as di(2-ethylhexyl) phthalate (DEHP), are metabolized into their respective monoester metabolites (MEHP), which can be further metabolized to oxidative products such as phthalic acid (PA) and hydroxy monoesters (OH-MEHP). Other phthalates, such as diethyl phthalate (DEP), are rapidly metabolized into their respective monoester metabolites (MEP) and excreted in urine. The metabolic fate of phthalates is important because some of their metabolites have been associated with potential health risks, including endocrine disruption, reproductive and developmental toxicity, and cancer. The extent and duration of phthalate exposure, as well as individual metabolic capacity, can also impact the levels and persistence of phthalate metabolites in the body.

What’s the harm of phthalates?

While phthalates is a huge class of chemicals and nowhere near every chemical in the class has been studied yet, several have been shown to have negative health impacts. The systematic review and meta-analysis done by Jaakkola et al.[4] found that exposure to phthalates from polyvinyl chloride products is associated with an increased risk of asthma and allergies. Wormuth et al.[5] have conducted research that highlights the potential health risks associated with exposure to phthalates, particularly for vulnerable populations such as pregnant women and children. For instance, phthalates can disrupt the endocrine system, which can interfere with reproductive and developmental processes. Exposure to phthalates has been associated with reduced fertility, decreased sperm quality, and adverse effects on fetal development. The study of Kim et al.[6] also found that exposure to phthalates is associated with an increased risk of attention deficit disorder and learning disabilities in children.

Figure 3. Potential negative health effects from phthalates exposure.

Phthalate exposure has been shown to cause liver and kidney damage in animal studies, although the evidence in humans is less clear. Some other studies have suggested a possible link between phthalate exposure and an increased risk of certain types of cancer, despite that the evidence is still inconclusive.

No escape and no fear

Friends or foes? Instead of this tricky question, we should think about how to treat phthalates in a long term sense. Both because of their ubiquitous usage and because they are not listed on product labels, phthalates are next to impossible to avoid. They are everywhere in all kinds of products and are so important as industrial components. Even for those who either avoid these products or buy phthalate-free variations, phthalates lurk in unexpected places.[3] However, concerning the negative health effects they might exert on humans and animals, the management and regulation of phthalates seem to be a tough issue.

The history of regulation for phthalates dates back several decades. In the 1970s, concerns were raised about the potential health effects of phthalates, particularly in relation to reproductive and developmental toxicity. As a result, several phthalates were banned or restricted in certain products in the United States and Europe. In 2008, the Consumer Product Safety Improvement Act (CPSIA) was passed in the U.S., which placed limits on the use of six phthalates in children’s toys and childcare articles. In Europe, the REACH (Registration, Evaluation, Authorization and Restriction of Chemicals) regulation was introduced in 2007, which requires companies to register and evaluate the potential risks of their chemicals, including phthalates.

Moving forward, the regulation of phthalates is likely to continue to evolve. In the U.S., there have been calls for greater regulation of phthalates in consumer products, including the use of the Toxic Substances Control Act (TSCA) to regulate phthalates as a class. The European Chemicals Agency (ECHA) has also proposed restrictions on the use of four phthalates in consumer products. Additionally, there is growing interest in alternatives to phthalates, such as non-phthalate plasticizers, which are perceived to have lower health risks. Overall, the direction of regulation for phthalates is likely to focus on reducing exposure to these chemicals in order to protect public health.

Reference

[1] Hauser R, Calafat AM. PHTHALATES AND HUMAN HEALTH. Occupational and Environmental Medicine 2005; 62:806-818.

[2] Ursel Heudorf, Volker Mersch-Sundermann, Jürgen Angerer. Phthalates: Toxicology and exposure, International Journal of Hygiene and Environmental Health, Volume 210, Issue 5, 2007, Pages 623-634, ISSN 1438-4639, https://doi.org/10.1016/j.ijheh.2007.07.011.

[3] Amy Westervelt. Phthalates are everywhere, and the health risks are worrying. How bad are they really? https://www.theguardian.com/lifeandstyle/2015/feb/10/phthalates-plastics-chemicals-research-analysis.

[4] Jaakkola, J. J., & Knight, T. L. (2008). The role of exposure to phthalates from polyvinyl chloride products in the development of asthma and allergies: A systematic review and meta-analysis. Environmental Health Perspectives, 116(7), 845-853. doi:10.1289/ehp.10952.

[5] Wormuth, M., Scheringer, M., Vollenweider, M., Hungerbuhler, K., & Schmid, P. (2006). Environmental risk assessment of phthalate esters: A review of the scientific literature. Environmental Health Perspectives, 114(Suppl. 1), 61-68. doi:10.1289/ehp.8049.

[6] Kim, S., Cho, S. I., & Kim, J. H. (2015). Association between phthalates and attention deficit disorder and learning disability in U.S. children, 6-15 years. Environmental Research, 137, 221-228. doi:10.1016/j.envres.2014.11.001