Have you heard of PFAS? Standing for “Per- and Polyfluorinated Substances,” PFAS is the generic name for artificially created organic fluorine compounds. Capable of repelling water and oil, in addition to being highly resistant to heat, chemicals, and ultraviolet rays, they are used in a wide range of applications from water repellents and emulsifiers, to fire extinguishing agents and surface treatments for packaging materials. However, as stable compounds, PFAS have also become known as “forever chemicals” since they can remain in the environment with little degradation. Reportedly, some PFAS may potentially affect human health if people are internally exposed to them for long periods of time. In recent years, there has been an accelerating trend toward their tighter regulation, particularly in the US and Europe. In this newsletter, we asked Dr. Kouji Harada, Associate Professor at the Department of Health and Environmental Sciences, Graduate School of Medicine, Kyoto University, to introduce some of the fundamentals around PFAS, as well as share his insights into related domestic and international trends, and what approach the healthcare industry should take. Read on to the end for Dr. Harada’s profile.

PFAS are used in a wide variety of products and manufacturing processes

What kind of substances are PFAS exactly?

PFAS is the generic name for “organofluorine” compounds. There are at least 4,700 of these, with one theory putting the number above 10,000. Some are known to pose health risks to the human body, with the US National Academy of Sciences currently deeming seven types of PFAS as high-risk health hazards.¹ A variety of industries have been using PFAS-based products in their manufacturing processes and end products since the 1940s thanks to their ability to repel water and oil, as well as to resist heat and UV light.

Specifically, PFAS are found in industrial products and manufacturing processes, and some applications include being used as water repellents, surface treatment agents, emulsifiers, fire extinguishing agents, and coating agents. Familiar examples include the coating on non-stick frying pans or the wrapping paper for fast food meals such as hamburgers and fries due to the heat and oil resistance offered. The healthcare industry is also affected since they can sometimes be found in pharmaceuticals and medical devices.

Why are PFAS a problem?

PFAS are considered “stable” substances. This means that once released into the environment, they continue to remain there with little degradation. For this reason, they are often referred to internationally as “forever chemicals,” although this is not an academic term. PFAS may be taken into the body through tap water, soil, agricultural products, and seafood. As they cannot be broken down by the human body, it can take many years before they are fully excreted.

The effects of PFAS on the human body first came to public attention in the late 1990s, when a class action lawsuit was filed by residents in the United States. A plant that had been manufacturing fluoropolymer processed products for many years was sued by local residents for causing groundwater and soil contamination with PFOA (perfluorooctanoic acid), a type of PFAS. The case was settled out of court in 2003. Local residents were given health surveys for approximately 10 years afterwards as part of the settlement. The study found an increased risk of dyslipidemia, thyroid disease, pregnancy-induced hypertension, low birth weight, kidney cancer, and testicular cancer. Later studies around the world confirmed similar risks.

Can PFAS be easily ingested from tap water?

It depends on the situation. If the groundwater is contaminated, there is a likelihood of it being ingested via the local tap water. Those who routinely handle PFAS-containing materials for their work are also more likely to be exposed. People may also ingest them after eating crops grown on contaminated soil or fish taken from contaminated lakes and marshes. In each case, it is necessary to understand that PFAS do not cause symptoms of poisoning immediately after ingestion; the effects on the human body are long-term, and should be planned for accordingly.

Implementing regulations around the world

How are other countries responding to PFAS?

Globally, it is mostly the US and Europe that have begun to tackle these health hazards by implementing water quality regulations. In Japan, the Ministry of Health, Labour and Welfare (MHLW) set a provisional target in 2020 of no more than 50 nanograms of PFOA and PFOS (perfluorooctanesulfonic acid) per liter of drinking water, covering two PFAS of particular concern as health hazards.² Many municipalities are now beginning to monitor their tap water. In the US, a very strictly enforceable regulatory target of 4 nanograms per liter of drinking water for both PFOA and PFOS was proposed in March 2023.

On the other hand, we know that PFOA and PFOS concentrations in blood can be halved in three to five years if exposure is eliminated. With international treaties banning the production, use, and import of PFOA and PFOS; a worldwide movement toward greater regulation; and companies promoting voluntary regulation, we’ve seen PFOA and PFOS concentrations in the blood of residents in many areas in Japan enter a general downward trend. However, it’s important to remember that once a location is contaminated, PFOA and PFOS can remain in the area for long periods of time (10 to 20 years). Recent studies show that the residents’ blood PFOA and PFOS levels remain high in certain areas, indicating a continued large regional difference.

Can anyone take a blood test?

General clinical laboratory tests do not support the measurement of PFAS concentrations in the blood. Another bottleneck is the extremely high cost of the test, which requires a mass spectrometer and is therefore several tens of thousands of yen per sample. Naturally, this is a considerable burden for the individual to bear. In the US, guidance on blood levels (by the aforementioned US National Academy of Sciences) has been published, but the infrastructure for widespread testing of blood levels is not in place. Creating an alternative simple measurement method using a conventional immune response method would therefore be a major innovation.

What can be done if blood levels are found to be high?

There are currently no drugs that accelerate the breakdown of PFAS ingested into the body, and no treatment (such as apheresis) is recommended to actively promote its excretion from the body. Given the indications that long-term exposure increases the risk of developing diseases (dyslipidemia, thyroid disease, gestational hypertension, low birth weight, kidney and testicular cancer), the National Academy of Sciences’ clinical guidance, published in August 2022, states that for individuals with high blood levels of PFAS, physicians should “provide medical care, treatment, and measures to reduce exposure with the increased risk of developing these diseases in mind.” In Japan, there has been a movement to establish outpatient clinics in areas where residents have high blood levels of PFAS, but the basic treatment policy remains the same as standard treatment policies for these diseases.

What PFAS measures are required of the healthcare industry?

Please tell us more about what the healthcare industry can do.

As mentioned, there are examples of PFAS being used in healthcare industry manufacturing processes, including pharmaceuticals and medical devices. Fluorine is an important substance for regulating the stability and efficacy of pharmaceuticals, some of which contain structures that can be classified as PFAS. Of course, not all PFAS pose a health risk. In some cases, there may not yet be an available alternative substance. The healthcare industry will need to manage manufacturing processes to avoid releasing PFAS into the environment; carefully evaluate the risks and benefits when they are essential for manufacturing or used in end products; prove the safety of the PFAS they are using; and disclose information to consumers to gain their full understanding of the product.

Further regulatory developments are also underway. For example, in February 2023, the European Chemicals Agency (ECHA) published a strong regulatory proposal to “restrict the manufacture, marketing, and import of all PFAS after a certain period of grace.”³ The grace period is 18 months, while an additional grace period of 5 to 12 years can be given as a special exception for medical devices with a proven need. Although it remains to be seen whether the proposal will be adopted as is, healthcare companies active in the global market should anticipate similar regulatory developments and consider how they can secure alternatives with a goal of becoming “as PFAS-free as possible” going forward.

How should we face the issue of PFAS in the future?

The issues surrounding PFAS are still in the process of being clarified. Again, not all of them pose a risk to human health. However, the reality is that worldwide, regulations are being implemented ahead of schedule based on an understanding that we cannot simply wait for the toxicity of all 4,700-plus PFAS to first be clarified. In fact, in Europe and the US, the upper limits for drinking water PFOA and PFOS concentrations were significantly further tightened after it was discovered that even small amounts could pose a health risk. As individuals, we can check the PFOA and PFOS content of our tap water on the websites of the respective municipalities in which we live, or install simple water purification filters if you are concerned about this issue. It is difficult for individuals to change such environmental issues as ultimately the onus is on the government. However, I believe it is important for each of us to be concerned about the issue, seek to correctly understand it, and act on it accordingly.

Profile: Dr. Kouji Harada, PhD, MPH Associate Professor, Department of Health and Environmental Sciences, Graduate School of Medicine, Kyoto University A graduate of Kyoto University’s Faculty of Pharmaceutical Sciences, Dr. Harada went on to gain his PhD in Public Health from Kyoto University, completing a doctoral program at the Graduate School of Medicine. After working there as an assistant professor, he became an associate professor in 2009 and has served as a member of the the Ministry of the Environment’s Expert Committee for the Comprehensive Strategy on PFAS since 2023.

Dr. Harada’s research page:
https://plaza.umin.ac.jp/khh/index.htm

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