Per- and Polyfluoroalkyl Substances (PFAS)

Q: Why does NTP care about studying PFAS?
A: All PFAS contain carbon-fluorine bonds—one of the strongest in nature—making them highly persistent in the environment and in our bodies. Therefore, NTP is studying PFAS given that PFAS are found to have:

• Widespread exposure to humans
• Observed toxicity in animal models
• Insufficient information to properly assess human health risk across the entire structural class

Q: What are some commonly used terms for PFAS?
A: Per/polyfluoralkyl substances (PFAS) is the preferred term for this class of chemicals, but other commonly used terms for PFAS include:

• Perfluorinated chemicals
• Perfluorochemicals
• Perfluoroalkyls
• Perfluorinated alkyl acids
• Polyfluorinated chemicals
• Polyfluorinated compounds
• Polyfluoroalkyl substances

Q: Where does PFAS exposure come from?
A:

• Food packaged in PFAS-containing materials, processed with equipment that used PFAS, or grown in PFAS-contaminated soil or water.
• Commercial household products, including stain- and water-repellent fabrics, nonstick products (e.g., Teflon), polishes, waxes, paints, cleaning products, and fire-fighting foams (a major source of groundwater contamination at airports and military bases where firefighting training occurs).
• Workplace, including production facilities or industries (e.g., chrome plating, electronics manufacturing or oil recovery) that use PFAS.
• Drinking water, typically localized and associated with a specific facility (e.g., manufacturer, landfill, wastewater treatment plant, firefighter training facility).

Q: What do we know so far about PFAS?
A: The scientific understanding of the health effects of PFAS compounds comes almost entirely from studies on a select few. Long-chain perfluorooctanoic acid (PFOA) and perfluorooctane sulfonate (PFOS) have been manufactured the longest, are the most widespread in the environment, and are the most well-studied PFAS to date. Their use has been phased out in the U.S., but these chemicals are still manufactured in other countries. Studies indicate that PFOA and PFOS can cause reproductive and developmental, liver and kidney, and immunological effects in laboratory animals. Both chemicals have caused tumors in animals.

A wide range of short-chain PFAS, including PFBS and PFHxA, have been introduced recently as alternatives to their long-chain counterparts. The health effects of these chemicals are far less studied.

Studies in animal models show that some PFAS can cause reproductive and developmental, endocrine, liver and kidney, and immunological effects. PFOA and PFOS have caused tumors in animal studies.

The most consistent findings from human epidemiology studies are increased cholesterol levels among exposed populations, with more limited findings related to:

• infant birth weights,
• effects on the immune system,
• cancer (for PFOA), and
• thyroid hormone disruption (for PFOS).

Q: Why does NTP study PFAS in rodent models and human cells?
A: NTP studies the potential health effects of PFAS in many different ways, including experimental rodent and cell-based test systems, literature review, and computer modeling, among others. While experiments in cells and in animal models are often done at doses higher than would be measured in a human, and the biology between a rodent model or cell to a human may differ, the findings are still valuable for providing insights into how PFAS may impact human health.

Q: What is the difference between short-chain and long-chain PFAS and legacy versus newer PFAS?
A: Long-chain PFAS have more than six carbons in their chemical structure, while short-chain PFAS have fewer than six. Some have asserted that short-chain PFAS may be safer than long-chain PFAS. Legacy PFAS generally includes PFOA and PFOS, which are no longer manufactured in the United states, while GenX is an example of a newer PFAS.

Q: Why is studying PFAS challenging?
A: While many research projects focus on a single or series of PFAS, current human exposures to PFAS involve complex mixtures, not individual chemicals. This complicates both the science of exposure measurement and the assessment of health risks. Current analytical techniques are limited for determining which specific PFAS are in a given mixture. Additionally, health impact information for combined PFAS mixtures is not well understood.

Q: Who nominated PFAS to be studied by NTP?
A: The U.S. Environmental Protection Agency (EPA) nominated the PFAS class to NTP for studies on potential health effects of these chemicals.

Q: What is the REACT Program?
A: The NTP Responsive Evaluation and Assessment of Chemical Toxicity, or REACT, Program is broadening our understanding of PFAS by studying over a hundred compounds that fall into different subclasses based on similarities in chemical properties. Scientists will be able to compare one PFAS to another, determine the relationship between chain length and other structural features and toxicity, and inform on whether there are common or overlapping patterns of toxicity. There are a variety of studies taking place within the REACT program including:

• Hepatotoxicity: Evaluation of potential liver toxicity using human liver cells
• Hepatic Clearance: Evaluating the clearance or removal of PFAS chemical using human liver cells
• Renal Transport: Screening potential kidney transport of various PFAS chemicals, a mechanism believed to contribute to the time it takes to clear PFAS from the body
• Mitochondrial Toxicity: Evaluate potential mitochondrial toxicity in human liver cells
• In Vitro Disposition: This collaborative project incorporates various screening methods to complement the in vivo PFAS studies at NTP

REACT uses a combination of approaches. One project analyzes the chemical structure of PFAS compounds to see what information is available in databases for that compound or others with similar structure. Structure plays a major role in how chemicals interact, and chemicals with similar structure often have similar toxicity. This computer-based step is known as in silico screening. Based on in silico results, chemicals can be selected for further targeted laboratory testing with cells, known as in vitro testing. Examples include testing whether PFAS cause cells to die or substantially alter the function of human liver, placenta, or mammary gland derived cells. Some of these tests are similar to, or a refinement of, those used in the automated Toxicology in the 21st Century (Tox21) Program, a federal collaboration among the NIH, U.S. Environmental Protection Agency (EPA), and U.S. Food and Drug Administration (FDA). The in vitro data are then examined to prioritize select chemicals for toxicity testing in animals, known as in vivo studies, so the data can be considered all together. REACT is a collaborative program with EPA. Both NTP and EPA are contributing complementary resources to coordinate and share what is learned about individual chemicals.

Q: What other federal agencies is NTP collaborating with on PFAS research?
A: NTP is communicating its efforts with other federal agencies such as the U.S Environmental Protection Agency (EPA), Food and Drug Administration (FDA), Consumer Product Safety Commission (CPSC), Department of Defense (DOD), and Centers for Disease Control and Prevention (CDC)/Agency for Toxic Substances and Disease Registry (ATSDR) to ensure that NTP research planning considers information needs for these agencies and program areas.

• NTP Board of Scientific Counselors Meeting, Research Triangle Park, NC, December 7-8, 2017
  • Background Materials: The NTP Rapid Evaluation and Assessment of Chemical Toxicity (REACT) of Polyfluorinated Alky Substances (PFAS) Project
  • Slides: Rapid Evaluation and Assessment of Chemical Toxicity (REACT): Per- and Polyfluoroalkyl Substances (PFAS)