Tag: PFAS

PFAS Forensics

This article covers the basics of PFAS Forensics and other Environmental Forensics.

Look a crime scene looking person examining soil! Must be PFAS forensics – even if I used the photo from an article titled: “How did we fall for the Junk Science of Forensics”

Depending on whom you speak with the term forensics can be a dirty word. It either conjures up images of flawed feature-comparison disciplines (hair-, bite-, or tool-mark comparisons for example) underlined by poor science or single source DNA which exonerates the falsely accused. PFAS forensics, when practiced well, more closely resembles DNA evidence for a criminal case and may play a critical role in ensuring those responsible for contamination pay for its remediation. The purpose of this article is to provide a gentle introduction to environmental forensics with an emphasis on PFAS. This is just one of several articles I have written on PFAS, it may help to refresh on PFAS terminology as well as PFAS analytic strategies. I am acting in my own capacity, my views are my own and do not represent my employer. Nothing here constitutes legal or professional advice.

About 99.9% of DNA between humans is the same however, scientists have characterized DNA regions that are different between people who are not closely related. Forensic labs look at 20 DNA regions that vary between individuals, called short tandem repeats (STRs), to create a DNA “fingerprint.” The chance that two people who aren’t closely related have the same DNA profile is 1 in 1,000,000,000,000,000,000. Paraphrased from Mary May and figure by Rebecca Clements

Introduction to PFAS Forensics

PFAS forensics is not a bunch of EPA investigators playing “good cop bad cop” with a chemical manufacturer or waste manager tied to a chair with a bright spotlight shining in their face. PFAS forensics is the subset of environmental forensics which deals with PFAS. Environmental forensics more generally is really the logical outgrowth and terminus of one branch in fate and contaminant transport. While fate and contaminant transport in general describes how chemicals move and transform throughout the environment, when this is reframed through the lens of forensics the emphasis shifts from more describing mobility and persistence to assist in assessing exposure more to source identification/attribution as well as developing legal along with scientific defensibility of conclusions. With billions on the line in multidistrict litigation you can bet the science will be heavily scrutinized.

PFAS forensics is not the Reid Technique aka “good cop bad cop” instead it is really a different focus for traditional fate and transport

Basic PFAS and Environmental Forensics

Environmental forensics, and by extension PFAS forensics, typically has a few routine questions:

  • Who is responsible for the PFAS?
  • When and how was the PFAS released?
  • In cases with more than one responsible party: How much has each party contributed?
  • Were the releases progressive or sudden?

Environmental forensics uses several techniques to answer these questions to tease out information about how the contaminant (PFAS in this case) got to the place where it was detected. In many cases multiple releases of the same or related chemical are from the same site which may require contribution allocation for each identified release – this is especially important where more than one responsible party is identified. Beyond obvious applications in litigation, PFAS forensics could potentially lead to cost savings by better characterizing the sites and understanding related risks from them, better tailoring remediation or treatment, and assisting in insurance claims. In some cases, environmental forensics has also lead to completely new discoveries. For example, an unknown natural perchlorate source, unrelated to nitrate from the Atacama Desert or other known sources, was discovered using isotropic fingerprinting during a forensic investigation launched after routine perchlorate monitoring discovered contamination north of San Diego. While a PFAS forensic study may be solved using only one technique it is important to build multiple independent lines of evidence consisting of at least two distinct techniques to check your work. The independent evidence should obviously point to the same conclusion. Cases where one line of evidence is enough tend to include straightforward reported releases or dumping.

Common Non-Intrusive Environmental and PFAS Forensic Techniques

When performing document review, it’s critical to pay attention to chemicals which while may not pose health risks may be linked to the original health contaminant as an additive or may influence the fate and transport of the contaminant of concern. Site features such as underground storage tanks, https://www.epa.gov/ust ditches, loading docks, transformers/electrical components (especially for PCBs) are also important.

  • Historical document review which can include historical documents (deeds, spill, or ownership records), environmental permits, operational or monitoring data, shipping manifests, as well as sales or invoices can be extremely helpful. These can also assist in recreating production processes if no records exist.
  • Photographic review is very valuable. Systematic coverage of the US has occurred since the 1930s and changes overtime can be very instructive. The Aerial Photography Field Office of the USDA is particularly valuable and infrared photography can also assist in differentiating vegetation changes.
  • Map review which can denote things such as waste or chemical storage, loading/unloading areas, warehouses etc… Sanborn maps (fire insurance maps) are particularly useful.
  • Interviews with current and past employees, neighbors, or other relevant parties can provide clues to focusing the search or turn up undocumented knowledge.
  • Market forensics started due to diffuse releases, for example in consumer products. Essentially sales and other relevant product information (eg formulation) is aggregated to estimate total loading. Market forensics has been successfully used on a local scale to determine fatty alcohol (detergent) contamination in Luray, Virginia (home of the caverns). I believe this to be most accurate for PFAS on a global scale as some emissions inventories have shown. In most instances on local scales it is closer to bite mark analysis (forensic odontology) than DNA analysis.

A whole review industry has sprung up from historical review in the form of EPA Phase 1 Environmental Site Assessments compliant with the All Appropriate Inquires Rule from 40 CRF 312. This can be considered defensive due diligence when performed prior to a real estate transaction.

A document review conducted according to the All Appropriate Inquires rule can serve as liability protection and should be the first step in any forensic investigation. Image from Digital WarRoom

Advanced Environmental and PFAS Forensic Techniques

Non-intrusive techniques alone may be enough to end investigations into PFAS sources however, sometimes more advanced techniques are required.  These advanced techniques should only be undertaken after integrating any existing knowledge body related to a specific site because advanced techniques are often costly.

Chemical Fingerprinting

Chemical fingerprinting is where specific sources are associated with characteristic distributions typically developed through comparison source samples or a priori knowledge developed using non-intrusive techniques. Chemical fingerprinting has successfully been used for PFAS source identification several times.

Specific chemicals can develop a “fingerprint” for specific sites and introduces some challenges to that technique in the form of unknown precursors
This fantastic image from Per- and polyfluoroalkyl substances in Chinese and German river water – Point source- and country-specific fingerprints including unknown precursors does an excellent job showing how testing for specific chemicals can develop a “fingerprint” for specific sites and introduces some challenges to that technique in the form of unknown precursors. Manufacturing sites are plotted and labeled in the left panel, their specific chemical fingerprint as percent of total load is given in the center panel, and the TOP assay was used to show that some of the targeted endpoints were from untargeted unknown precursors

Isomer Analysis

Isomer analysis, isomers are compounds with the same formula but differing chemical structures. PFAS are generally produced through either electrochemical fluorination (ECF) or telomerization. ECF products contain approximately 70–80% linear structures and 20–30% branched isomers; telomerization yields relatively pure linear or isopropyl branched isomers. This technique also has been used several times for PFAS source identification.

Isomers elute at different points during HPLC. Branched forms of PFAS elute after linear PFAS and the more branched it is the slower it typically elutes.
Isomers elute at different points during HPLC. Branched forms of PFAS elute after linear PFAS and the more branched it is the slower it typically elutes. Image from Eurofins

Chiral Analysis

Chiral analysis is a very unique subset of isomer analysis. The easiest way to think about chiral isomers, or enantiomers as they’re also known, is your right and left hand. Your hands are the same “isomer” except for an asymmetry so if you line your hands on top of each other palms down they do not match however, palms together they do.  This is the same concept behind chirality. Manufactured compounds (such as PFAS) are racemic mixtures which means they contain the same or near equal enantiomer ratios. Since enzymes are always chiral, biotransformation is normally enantioselective. Chiral analysis can show if biotic uptake is due to precursors or direct source and has been used for this purpose. While I am not aware of any studies, this kind of analysis may also be able to differentiate weathering and precursor transformation for example between manufactured PFOA against PFOA degraded from fluorotelomer alcohols.

PFOA enantiomers which can be helpful in elucidating precursor loading
PFOA enantiomers which can be helpful in elucidating precursor loading

Isotropic Analysis

While isomers have the same chemical formula but distinct structures; isotopes are elements that have the same atomic number but different atomic mass. Isotopic Analysis means techniques measuring the mass of different stable isotopes, typically carbon, hydrogen, oxygen, nitrogen, and chlorine although there are many other possibilities. Unless something is ionized its protons must balance charge with electrons however, neutrons, which carry no charge, affect the weight allowing for this type of analysis. There are three main Isotopic Analyses which fall into this category: bulk, compound specific, and positional specific.

Elements are tracked by protons, unless an atom is ionized, the charge must balance so protons equal electrons; the neutrons may vary in stable compounds which is the basis for Isotopic Analysis
Elements are tracked by protons, unless an atom is ionized, the charge must balance so protons equal electrons; the neutrons may vary in stable compounds which is the basis for Isotopic Analysis

Bulk Stable Isotropic Analysis (BSIA)

Bulk Stable Isotropic Analysis is a specific type of isotropic analysis that measures the total concentrations of stable elements in a sample and can be correlated to the specific element in the releasing source. While I do not know any direct applications to PFAS yet, this technique has been used before to combat pharmaceutical counterfeiting.

Root and within plant uptake may be fractionating processes
The assumption that root water uptake and within-plant water transport are non-fractionating is slowly crumbling. Several studies such as this one from Javier de la Casa have reported offsets between plant and source water stable isotope composition. Without proper accounting, these isotopic offsets can result in the erroneous source water attribution and uptake overestimations by vegetation. This image shows a shift in soil water excess against line conditioned excess the green dots are where both LC-excess and SW-excess plus the corresponding standard error were negative.

Compound specific isotopic analysis (CSIA)

Compound specific isotopic analysis (CSIA) is isotropic analysis for specific compounds (for example PFOA) within a sample and is generally much more powerful a method. This is in the process of being applied to PFAS, through Strategic Environmental Research and Development Program (SERDP) and Environmental Security Technology Certification Program (ESTCP) project ER24-4239.

Isotope signatures can allow different contaminant sources to be distinguished at the same site
While CSIA is not yet proven for PFAS, analogies can be drawn to chlorinated solvents. Since several manufacturing processes and raw materials are used to make chlorinated solvents each solvent tends to have different δ13C, δ37Cl and δ2H signatures for specific VOCs which can allow distinguishing different contaminant sources at the same site, identifying a contaminant from an off-site source located upgradient, as well as establishing links between observed compounds and emitting sources. Image courtesy of Terus Environmental

Position specific isotopic analysis (PSIA)

Position specific isotopic analysis (PSIA) provides stable isotope ratios at each carbon position where a C–F bond is present. This has been done with PFAS in the lab and theoretically is the most powerful isotopic analysis method available.

Position specific isotopic analysis (PSIA) is isotopic analysis at each bond
Figure showing PSIA for fipronil, a PFAS insecticide, which is blamed for spreading colony collapse disorder among bee colonies (along with neonicotinoid insecticides). Image courtesy of Cornelia Rasmussen and David Hoffman

Advanced Statistical Techniques

Advanced statistical techniques such as principal component analysis can also assist in forensic studies. PCA is designed to reduce a dataset to its principal components by taking an original dataset and finding a new smaller set of variables that still describes the most variance in the original dataset – that is to say to take the chemical inputs and reduce it to source inputs. PCA relies on eigen values and eigen vectors to reduce the dimensionality of a dataset.

This image shows two sources derived from several dimensions (chemical ratios)
A principal component analysis for PFAS profiles. The score plot is shown to the left and the loading plot is shown to the right. In the loading plot, PFCA are colored purple and pink, PFSA are colored green, and PFOS precursors are colored yellow. In this study PCA was used to aid in PFAS source identification.
Karl Pearson is a founding father of mathematical statistics
PCA was discovered in 1901 by Karl Pearson. Pearson was a brilliant but misguided statistician who founded mathematical statistics along with the world’s first statistical department but is also the poster child for scientific racism. Image from the American Statistical Association. I wonder why they didn’t decide to call themselves the American Statistical Society.

Dendrochronology

Dendrochronology, or dating tree rings, may provide inference on when PFAS releases first occurred, particularly for birch or spruce although I do not think this has been used in this way yet; most information revolves around phytoremediation. Dendrochronology may not yet meet the Daubert Criteria (some states still use the Frye Standard but all federal courts use Daubert) but there is some evidence for it.

Haglöf increment borer - a dendrochronology tool
Careful analysis on core parts can assist in developing timelines, while unproven for PFAS it has been used for petroleum and chlorinated solvents cases. Image from Britannica

Some PFAS Forensics Considerations

PFAS forensics is a rapidly evolving science with many unknowns. However, it can draw many parallels to petroleum forensics which has a very deep body of knowledge around it because of the environmental liability associated with petroleum. For example, both are made of complex chemical mixtures enabling chemical fingerprinting for ready source identification. Despite a varied chemical composition, there are a few constants with PFAS. For example, Perfluoroalkyl acids (PFAAs) are strong acids that are anionic at environmentally-relevant pH. PFAAs are extremely persistent in the environment and do not degrade or transform under typical environmental conditions polyfluoroalkyl substances include compounds that have the potential to transform into PFAAs and are known as precursors. Carbon chain length and functional moiety control sorption and therefore transport. High sorption capacity implies slower environmental transport and vice versa.

Major sorption potential of various types of PFAS with the defining characteristics listed on the sides
This image I made helps to show major sorption potential of various types of PFAS with the defining characteristics listed on the sides.

Some specifics that make PFAS forensics unique are:

  • With no known natural formation there is a source responsible somewhere.
  • Formulation can help establish dates. PFAS are entirely anthropogenic first starting in 1938 with several types not produced till much later. Presence of ether-ified PFAS, such as HFPO-DA (GenX Chemicals), for instance implies a 2000s source at the earliest.
  • Broad industrial use means many sources exist and differentiation may be important.
  • PFAS typically had industrial formulations to meet performance standards eg being able to extinguish a fire in a set time and not chemical composition standards so the chemical composition varies through time. In other words PFAS formulation depends on production year. Commercial formulation and usage profiles can identify sources.
  • Individual PFAS measured are only a fraction of total PFAS.
  • Lowered measured concentrations lead to increased uncertainty.
  • Due to long range transport capabilities, PFAS are ubiquitous global contaminants. For instance, rainwater has been found to exceed the new PFAS drinking water regulation.
  • Transport properties can additional sources. For example, if PFOA is ahead of PFHxA it can indicated separate releases since the longer chained PFAS has lower transport capabilities.
Showing more mobile lighter PFAS leading plumes
This image I made helps to show how an example plume could look.
  • PFAS are generally resistant to weathering and transformation (hence the term “forever chemicals”) however, precursors may occur. For example fluorotelomer alcohols may transform into perfluoroalkyl carboxylic acids.
  • Ratios of precursors (such as FTOHs) to terminal end products (PFAAs) should increase (ie fewer FTOHs and more PFAAs) with time and distance from sources. There should be a precursor gradient in other words.
  • PFAS tend to accumulate at interfaces for example between bulk liquids and L- or D-NAPLs, soil/water, soil/water and the atmosphere and so forth. In fact, this tendency has lead to foam fractionation as a potential treatment method.
  • PFAS tend to accumulate in muscle as opposed to adipose (fat) tissue unlike most contaminants.
  • Linear compared to branched PFAS should increase with distance from point source because most Br-PFAS have a higher water solubility and faster biological elimination from organisms which also results in faster biotransformation closer to the source.
  • Due to biotransformation, specific environmental PFAS concentrations should not be used to predict biotic uptake (take total organofluorine into account).
  • Low water concentrations compared to biota (hence implied high bioaccumulation factors) can indicate that water is not the only source.
  • Age-dating may be possible using specific diagnostic ratios.
Summary of major patterns discussed in the article
Image from L. Trozzolo, TRC, and C. Higgins, Colorado School of Mines which summarizes some of the patterns discussed above.

Conclusion and Key Take Aways

Practically, it is impossible to remediate global PFAS contamination however, managing PFAS hotspots through forensic investigations may significantly reduce global contamination’s extent. There are many parallels which can be drawn between petroleum forensic investigations and PFAS as well as many well-developed techniques to assist in source identification however, it is still a rapidly evolving field. The goal of PFAS forensics, and really environmental forensics, is ultimately to develop legal as well as scientific defensible conclusions related to source attribution. To that end, multiple independent lines of evidence should be used to validate and strengthen conclusions. If you learned something or enjoyed this article (I know I separated those but for me they tend to be correlated!) take a look at some other articles I have written on PFAS.

The Draft WHO PFOS and PFOA Guidelines for Drinking Water Quality

WHO logo
The World Health Organization is considering comments for the updated Guidelines for Drinking Water Quality.

The World Health Organization (WHO) is considering adding PFOA and PFOS into its Guidelines for Drinking Water Quality and is seeking public comment on their background document for development of WHO Guidelines for Drinking Water Quality.  This document is undergoing rolling revisions and accepting public comment using the form here sent to gdwq@who.int by 11 November 2022.  Guidelines for Drinking Water Quality are essentially the WHO’s version of the US EPA’s Health Advisories however, are 5 orders of magnitude higher with 100 ppt individual guidelines for PFOA and PFOS as well as a 500 ppt total PFAS guideline.  This 5 order of magnitude divergence between health agencies is primarily because the US EPA used epidemiological studies to define the reference dose while the WHO primarily relied on toxicology.  Relying on toxicology, the “WHO considered that the uncertainties in identifying the key endpoint applicable to human health following exposure to PFOS and/or PFOA are too significant to derive a HBGV with confidence” (page 79) while the US EPA did not have that issue.  The intent of this article is to go over what the WHO is, why it publishes drinking water quality guidelines, and the comments I submitted.  Please remember that my views are my own and do not reflect my employer’s position!

How the WHO's Guidelines for Drinking Water Quality are organized.
A summary of how the WHO’s Guidelines for Drinking Water are organized.

What is the WHO?

The WHO serves to coordinate and guide public health policy on a global level.  It started as the Office International d’Hygiène Publique (OIHP) or The International Office of Public Hygiene of President Wilson’s failed experiment, the League of Nations.  After the League of Nations folded on 20 April 1946 many of its functions were eventually rolled into the Untied Nations including the WHO. The WHO has been heavily criticized for decades such as by its former leaders and think tanks.  Criticism stepped up sharply during the ongoing corona virus pandemic. Despite all this, the WHO remains virtually the only true global consensus-building public health organization.  While its influence has weakened in recent years due to other global public health actors such as the World Bank or the Bill and Melinda Gates Foundation, it still is one of the most broadly recognized and supported organizations dedicated to public health.

Why does the WHO publish drinking water quality guidelines?

The WHO itself has been publishing drinking water quality guidelines since 1958 and in fact the WHO’s grandparents were the International Sanitary Conferences (ISC) first held on 23 June 1851 which were established as a result of a cholera pandemic.  The OIHP was initially established to carry out some of the ISC’s recommendations.  Cholera is a waterborne disease; a fact made famous by John Snow and the Broad Street Pump.  By removing a pump handle Dr. Snow helped deal a blow to the miasma theory of disease and served as a founding father to epidemiology; a subject I have a case study in.

John Snow is not only a Game of Thrones character
Wrong John Snow

Outside of this historical context, access to safe drinking water was voted a basic human right by the UN; whether or not a good/service can be considered a right is a discussion for a different day.  

What are the WHO Guideline Values?

The WHO currently recommends individual provisional guidance values of 100 ppt for PFOS and PFOA as well as 500 ppt for total PFAS.  These numbers exactly mirror the EU Drinking Water Directive and are substantially higher than the US EPA recommendations which are 0.004 ppt (or 4 parts per quadrillion) and 0.02 ppt (or 20 parts per quadrillion) for PFOA and PFOS respectively.  A key reason why these values are so dramatically different is that the US EPA considered epidemiological studies while the WHO did not.

The Thinker by Auguste Rodin
The Thinker by Auguste Rodin outside the Musée Rodin in Paris, thanks Wikipedia images.

Throughout the document the WHO uses older thoughts on PFAS and consistently cites the 2016 health advisories.  The US EPA has the most current human health toxicity assessments for PFAS however, the WHO consistently lists them last. 

On page 63 the WHO states (the numbers in the quote are line numbers for that page) “PFOA exposure is associated with clear 23 evidence of carcinogenic activity in male rats based on the increased incidence of liver 24 adenomas and pancreatic acinar cell tumours.” It is therefore not possible using current evidence 25 to exclude PFOA as a human carcinogen”.  This wording reflects the US EPA’s 2016 position; more recent human and animal studies lead the US EPA to conclude that PFOA is a more potent carcinogen than previously thought.

I am not enough of a health scientist to know or provide a meaningful analysis on the health aspects of the document other than the superficial one I just provided pointing out the WHO is using older science. Normally in the debate between epidemiology and toxicology, toxicology points to a more dangerous substance than the epidemiological studies.  Here, due to the preferred analysis by these organizations it appears to be flip flopped.  I would personally prefer to err on the side of caution; especially since drinking water according to the UN is a fundamental human right.

Why I submitted comments to the WHO

Simply put the WHO generally listens if you have a well thought out valid point which conforms to their purpose.  During their last request for comment I (and probably quite a few other people) made quite a few recommendations which were incorporated into this draft document.  For example, I recommended they:

  1. Take into account Xiao’s paper which shows that PFAS can be generated during advanced oxidation processes.  This also changed their practical considerations on monitoring so was quite a substantial change to the document.
  2. Take out the octanol water partitioning coefficient (Kow) from their table of physicochemical properties because PFOA and PFOS are both hydro- and lithophobic so bifurcate into its own layer between octanol and water. Although some people report values, these values are not reflective of the ground truth since the standard test was not designed for that type of material.  They also changed some of the other values such as the boiling point and melting point because the predicted range was larger than the experimental range. 
  3. Specify that anion exchange deals with anionic PFAS since there are cationic and neutral PFAS so there were some changes to those sections as a result.
  4. Drop the “s” from the PFAS acronym for plurals because a substance cannot simultaneously be per- and polyfluorinated so the plural is already implied.
  5. Use the OECD definition of PFAS which they updated.
  6. Use updates I provided on page 71 about characterizing EPA methods 533 and 537.1

One of my comments was almost incorporated word for word on page 74 related to chain length and functional group removal efficacy; a conclusion I partially took from this Sörengård et al. paper.

Previous comments which were not accepted

Not all my previous comments were accepted.  This goes to reflect that two people can look at the same data and draw different conclusions. Especially when the topic is a matter of policy there is often no “correct” answer although there are often clear cut “incorrect” answers. I am going to use this section to highlight some of the comments I made which were rejected, why I made those comments, and potentially the reason why the comment was rejected.  

  • I recommended against using percent removal as a characterization of process efficiency. You can think of properly designed granular activated carbon or anion exchange beds as towels wiping up liquid (contaminant).  When the towel is dry and the spill is small it picks up all of it quickly.  A wet towel mopping up a large spill may not clean everything or may not clean it quickly. Try and keep that analogy in mind for a contactor.  The photo below shows one mode for thinking of breakthrough.  Better ways to characterize the efficiency are to use media usage rate or bed life.  I believe that the WHO used percent removal because it makes it easier to compare to membrane filtration although again, I disagree with this characterization.
A schema of how breakthrough occurs in soprtive processes
This diagram shows one way of thinking about breakthrough although it is one of two main conceptual processes currently in the vouge.
  • I provided references which show greater removal percentages for sorption that the WHO quotes. There are many however, the US EPA drinking water treatability database captures many such examples.  The WHO is also much more pessimistic on anion exchange than I believe is warranted based on the data.  There are both full scale, pilot, and bench studies included. I do not really know why the WHO was cautious there compared to their membrane section where results were more often accepted at face value except potentially that was due to the declining efficacy over bed life which again, is why I suggested percent removal is a bad way to measure sorption process efficiency.
  • The WHO focuses on source water monitoring.  In general, this is a good approach however, I do not agree with it for PFAS.  PFAS is not known to and is unlikely to leach or permeate into drinking water supply.   Likewise, PFAS can be generated during treatment when advanced oxidation (and potentially advanced reduction) processes are used.  If resources are constrained it makes more sense to me to monitor the finished water rather than source water if only one is to be monitored especially since source waters are unlikely to change.  The counter argument is that only specific wells could be contaminated, and it would make sense to shut down those wells and not have to treat.  If you only monitor finished water, you will miss that level of detail.  If resources are constrained and you only monitor the influent, you’ll miss that anyway.  To me, this is a good example of two reasonable policy positions based on the same facts with divergent conclusions. 
  • In the previous document, the WHO referenced replacement chemistries; specifically short chained PFAS.  I recommended that esterified replacement chemistries be mentioned as well such as HFPO-DA (also known as GenX chemicals), ADONA, and Nafion byproducts.  Instead, the WHO removed references to replacement chemistries.  This is a good compromise because there are many replacement chemistries available.

My comments on the current draft

On this new draft the comments I have submitted to the WHO using their form emailing to gdwq@who.int (11 November 2022 deadline) are:

  1. The recommendation on page 70 that PFAS monitoring is only required when there is a reasonable source nearby is not protective of public health or in the best interests of society at large.  As this document points out PFAS is capable of long-range transport and deposition.  PFAS has been found in the artic and Antarctic as well as other remote areas.  Additionally, airports; military sites; landfills; wastewater treatment plants; carpet, upholstery, wax, and paper product manufacturers; or spreading biosolids (composting) are all PFAS sources.  Rasstadt, Germany was contaminated with composting from used food containers for example.  I do not believe that you can successfully perform a risk assessment given the diverse set of sources, low toxicity thresholds, and long-range transport capabilities.
  2. Page 72 lines 8-9 state (line numbers in parathesis): “Blending or diluting PFAS contaminated source water with uncontaminated water may be a (9) cost-effective and viable option for some water systems.”  As there is ultra-low toxicity and PFOA as well as PFOS have been identified as likely carcinogens I do not believe that deliberately exposing people to these contaminants through diluting or blending is an appropriate course of action unless there are no other alternatives such as treatment (this would be an economics question) or source substitution.
  3. Page 76 provides information on PFAS removal through sorptive technologies.  I believe, and have provided references above in this article, that significantly lower treatment standards are possible.
  4. On page 16 lines 27-30 it states (line numbers in quotes): “In 2019, the US EPA conducted a broad literature search to evaluate (28) evidence for pathways of human exposure to PFOA and PFOS, and in 2021 released a draft (29) analysis that supports application of a 20 percent relative source contribution for PFOA and (30) PFOS in drinking water (US EPA, 2021b,c).” This seems to overstate the strength of the conclusion the EPA made in those health advisories.  As I mention in this article, the EPA’s position was that there was insufficient evidence to deviate from a 20% default value; not that evidence supported a particular value.
  5. On page 4 line 37-39 it states (line number in parentheses): “PFOA remains possible, even where it is no longer (38) manufactured or used due to its legacy uses, degradation of precursors, and extremely high (39) persistence in the environment and the human body.”  I believe this is also true for PFOS and that disclaimer should be added to that section as well.
  6. Page 74 lines 45-46 deal with anion exchange resin regeneration.  Greater than 95% resin regeneration has been demonstrated in literature here, here, and here although it may not be practical for utilities from a safety and/or cost prospective.
  7. On page 9, the WHO references this Boone et al study; when the study was published the conclusion that only one monitored drinking water plan exceeded the EPA’s HAs was valid however, the HAs were updated.  That changes the study conclusion from one drinking water plan exceeding the EPA’s HAs to all quantitatively monitored plants exceeding the HAs, a significantly different conclusion.

Conclusion and Key Take Aways

Over time, scientific consensus points to greater and greater awareness of the dangers PFAS pose.  Generally, we thought these chemicals were safer in the past than most scientists do today.  The WHO, in its role as a policy leader, has developed a significantly less stringent health recommendation than even the old 2016 US EPA HAs on the dangers of these chemicals by not weighting epidemiological evidence the same way.  The WHO standard exactly mirrors the EU standard under the drinking water directive.  The WHO is a reasonable organization and solicits public comment and feedback as well as generally listening to it.  I highly recommend you share your opinions with the WHO regardless of whether you agree with me and take an active role in global public health.

Further Reading

This is one of several articles on PFAS I have written.  You can read about PFAS discovery, structure, or all my articles on PFAS.

PFAS Analytic Strategies

Stylized analysis of organic compounds using liquid chromatography
Image from Rocío L. Pérez and Graciela M. Escandar in “Experimental and chemometric strategies for the development of Green Analytical Chemistry (GAC) spectroscopic methods for the determination of organic pollutants in natural waters” showing mass spectroscopy. 

Introduction

Appropriate analytical methods are needed for toxicological and epidemiological studies as well as to enforce any restrictions. As alluded to in my article on PFAS structure, there is a not single definition for PFAS.  In fact from this 19 July 2022 federal register notice on the 5th Contaminant Candidate List and this proposed rule under section 8(a)(7) of the Toxic Substances Control Act it becomes clear that the EPA lacks a single PFAS definition within itself.  The EPA definitions are also different (and narrower) than the new July 2021 OECD report “Reconciling Terminology of the Universe of Per- and Polyfluoroalkyl Substances.” Many PFAS definitions are intentionally purpose written making one analytical method impossible to achieve. Additionally, there are many different PFAS types; the most commonly known ones are the anionic PFAS but there are also cationic and zwitterionic (both positive and negative functional groups). Given these two difficulties an immediate question should be how we measure these compounds.  This article intends to cover the broad strategies taken to measure PFAS and some of the methods within each as well as the methods’ strengths and weaknesses.  It focuses on anionic non-polymeric PFAS.  It may be helpful to review the article on PFAS nomenclature.

Summary

In general, there are three broad strategies for PFAS analysis:

1. Target analysis

2. Total fluorine (organic fluorine) methods

3. Non-target analysis including suspect screening and the total oxidizable precursor (TOP) assay (TOPA)

PFAS analysis is severely complicated by the prevalence of fluorochemicals in laboratory equipment particularly PTFE.  For example, PFAS is widely prevalent in HPLC solvent inlet tubing and PFAS from felt tip permanent markers used to mark containers during sampling campaigns.

Target analysis summary

Target analysis targeted methods typically involve either liquid or gas chromatography (LC or GC) coupled with mass spectrometry (MS) and require a reference standard for quantification. Standards are only available for select PFAS and only these specific substances can be quantified. Target analysis yields accurate concentrations but does not provide the total PFAS load.

Total fluorine methods summary

Fluorine is a sum of its inorganic and organic constituents; this insight forms the basis for quantification attempts by total fluorine methods.  As PFAS are organic molecules, inorganic fluorine is typically removed from the analysis and absorbable or extractable organic fluorine is measured. Due to differing chemical properties among PFAS, the extraction method chosen will not be suitable for all PFAS classes. Absorbable organic fluorine relies on choosing a suitable absorbent so suffers from the same difficulties.

Non-target analysis summary

Non-target analysis uses chromatography coupled to a high-resolution mass spectrometer and can identify previously unknown PFAS. These methods tend to rely on quadrupole time-of-flight and linear ion trap-orbitraps which are not common instruments. If reference standards are available, similar detection limits to targeted analysis can be achieved. The TOPA deserves special mention as this method performs targeted analysis then attempts to oxidize all precursor compounds into compound endpoints which have standards then performs targeted analysis again to see the difference and theoretically quantify the precursor load but not the specific precursors. These methods suffer from the high technical capacity and equipment required to employ them.

Targeted Analysis

Targeted analysis is currently the only form of analysis which can support drinking water regulatory action because it is able to quantify extremely low PFAS levels; generally around 4 parts per trillion (ppt). In general, LC-MS/MS or GC-MS/MS is used. Reference standards are only available for select PFAS so only select PFAS may be quantified. Which PFAS have standards is driven both by the ability to synthesize extremely high purity samples, regulatory emphasis, and economic viability for the producers. The main PFAS which have standards are per- and polyfluorinated acids (PFAA) – particularly the carboxylic (PFCA) and sulfonic acids (PFSA) as well as the etherified versions of these.  As a quick reminder PFCA end in “O” such as PFOA and PFSA end in “S” such as PFOS.  The etherified versions tend to have a less standardized nomenclature structure such as “GenX chemicals” or ADONA.

Targeted analysis is well established for various matrices.  For example, USEPA Methods 537.1 and 533 together cover 29 PFAS (537.1 focuses mainly on long chain PFAS and covers 18 while 533 was developed mainly to cover some more short chained PFAS and covers 25 PFAS; there are 14 PFAS which overlap between the standards).  The German Institute for Standardization (DIN) has also published standard methods DIN 38407-42 and 38414-14.  DINs are not freely available like the American methods so I will not link to a store here however, the DINs are broadly similar to the American methods.  All these methods use solid phase extraction (SPE) followed by liquid chromatography tandem mass spectrometry (LC-MS/MS). As these methods rely on solid phase extraction, the method efficacy declines with chain length.  In other words, the quantification and detection limits for short chained PFAS are higher than they are for long chained PFAS.

As mentioned in the nomenclature article, PFAS may come in “linear” or “branched” forms. These targeted methods may detect branched forms however, branched standards are not widely available and ignoring these will result in a low bias.  Linear to branched isomer ratios can also help to identify the PFAS sources. The USEPA Methods 537.1 and 533 include technical notes for dealing with branched isomers.

The DINs note that these methods can be extended to other PFAA with appropriate standard availability however, volatile fluorotelomers (like fluorotelomer alcohols) cannot be determined using these methods.

Comparison of which compounds can be detected by what EPA method
Comparison of EPA methods for PFAS determination in water; EPA 1633 (aqueous samples), EPA 537.1 (drinking water), and EPA 533 (drinking water). As you will notice the methods are broadly similar and will not work for volatile PFAS.

Total fluorine methods

Total fluorine (TF) is the sum of Inorganic Fluorine (IF) and Organic Fluorine (OF) sometimes called Total Organic Fluorine (TOF). TOF includes fluorine content of all PFAS and their precursors in the sample. TOF methods cannot however separate out organic fluorine contained in medications or other common uses from PFAS. There have been exceedingly few studies quantifying TOF fractions from PFAS compared to medications or other uses of organofluorine. Additionally, TOF methods have much higher quantification limits than targeted analysis, typically around 100 ppt. These two limitations make TOF methods suitable for screening but not protective enough of public health to seriously be used in drinking water regulation.  Remember the interim health advisories (HAs) for the apical effects of PFOA and PFOS were 0.004 and 0.02 ppt respectively, so 100 ppt is 4 or 5 orders of magnitude larger than the level at which no apical effects are expected. Additionally, organic fluorine methods only measure the fluorine while the HAs measure the full molecular weight. For example, PFOA (C8HF15O2) has a molar mass of 414.07 g/mol but the mass of fluorine only weighs approximately 285 g/mol PFOA meaning that only about 69% of each PFOA molecule would be quantified assuming perfect extraction and quantification.  The exact ratio of fluorine to the overall molecular weight is species dependent.

Organofluorine analysis requires the organic fluorine to be extracted – Extractable Organic Fluorine (EOF).  There will always be some organofluorine which cannot be extracted and some which can be extracted but cannot be quantified.  Extraction can be the same as for targeted methods. However, due to the large variability between the PFAS chemical composition, the extraction method will influence the test results. Likewise, similar to targeted methods, there is worse extraction efficiency for shorter chained PFAS and specific substances such as trifluoroacetic acid. A special EOF method is known as absorbable organic fluorine (AOF). During AOF, the sample is typically absorbed to a mixed-mode weak anion exchange SPE; again similar to targeted analysis methods.

The relationship between TF, TOF, EOF, and AOF.
Venn diagram showing the relationship between TF, TOF, EOF, and AOF. Image modified from “Determination of organically bound fluorine sum parameters in river water samples—comparison of combustion ion chromatography (CIC) and high resolution-continuum source-graphite furnace molecular absorption spectrometry (HR-CS-GFMAS)” by Gehrenkemper et al.

The most common total fluorine methods are: combustion ion chromatography (CIC), particle-induced gamma-ray emission spectroscopy (PIGE), instrumental neutron activation analysis (INAA), X-ray photoelectron spectroscopy (XPS), and 19F nuclear magnetic resonance spectroscopy (19F NMR).  Other methods are under development including: inductively coupled plasma mass-spectrometry (ICP-MS), continuum source molecular absorption spectrometry (CS-MAS), defluorination with sodium biphenyl (SBP), potentiometric and fluorimetric detection, and reversed phase LC-UV or GC coupled with a flame ionization detector (FID), electron capture detector (ECD), or MS.  CIC is currently the most discussed TF method.

Non-targeted Analysis

Non-target analysis for PFAS typically uses chromatography coupled to high-resolution mass spectrometers to identify previously unknown PFAS. These methods tend to rely on quadrupole time-of-flight and linear ion trap-orbitraps observed accurate masses, isotopic fingerprints, and MS/MS fragments. Accurate masses, isotope patterns, and molecular feature fragmentation patterns obtained from high resolution mass spectroscopy (HRMS) are compared to databases with known PFAS, such as the USEPA CompTox Chemistry Dashboard, NORMAN Suspect List Exchange, MetFrag, and STOFF-IDENT. Measured chemical responses are compared across two or more sample groups in a process known as fold-change comparison.

General workflow for non-target analysis
Image from Hollender et al. in High resolution mass spectrometry-based non-target screening can support regulatory environmental monitoring and chemicals management. This shows the general workflow for non-target analysis.

Total Oxidizable Precursor Assay

The Total Oxidizable Precursor (TOP) Assay (TOPA) was developed by Houtz and Sedlak in 2012 to quantify concentrations of difficult-to-measure and unidentified precursors of PFCA and PFSA in urban runoff. Essentially a sample is measured following conventional targeted analysis methods and then samples are exposed to hydroxyl radicals generated by persulfate thermolysis under basic pH conditions and measured following conventional targeted analysis methods again. Comparing pre- and post-oxidation concentrations the PFAA precursor load can be estimated. Unfortunately, oxidation conversion yields are compound dependent and many factors affect the oxidation process. Oxidation completeness can be tracked by adding a 13C mass labelled precursor however, this again is dependent on the specific compound chosen.  Additionally, the endpoint compounds selected for targeted analysis affect the results dramatically.  Activated persulfate does not generally oxidize PFSA so this can only really provide inference on PFCA precursors.  The TOP assay is also labor intensive, requiring twice the number of samples and more than twice the amount of work to produce a single result. The TOP assay does provide an indication of PFAS precursor load without requiring as advanced equipment or training as non-targeted analysis.

TOPA summary
Image from CDM Smith which summarizes the TOPA; essentially targeted analysis is run, precursors are oxidized as much as feasible and targeted analysis is re-run. An important point is that activated persulfate does not readily oxidize PFSA so it only really provides inference on PFCA precursors.

Conclusions

Each strategy selected for PFAS analysis carries with it its own unique strengths and drawbacks. Under most current toxicological frameworks employed by regulatory agencies targeted analysis is the only real viable option however, this can miss many PFAS. Total fluorine methods are several orders of magnitude too imprecise to accurately protect public health but capture most PFAS.  Non-targeted analysis methods require expensive equipment, much experience, as well as being non-quantified.

Further Information

This article is one of several on PFAS. You can read about PFAS discovery, structure, nomenclature, or my other PFAS articles.

PFAS Terminology and Nomenclature

Common PFAS terms
A word cloud containing some common PFAS terms. Made using Wordit.

Per- and polyfluoroalkyl substances (PFAS) are a ubiquitous emerging public health threat. PFAS terminology can be extremely confusing because it looks like an alphabet soup of similar acronyms. This article is the second of two on PFAS terminology. The first intended to provide an overview of PFAS structure (including what counts as PFAS), this one intends to help demystify PFAS terminology and nomenclature. These are part of a broader series on PFAS including their serendipitous discovery.

Introduction

PFAS are a large chemical class generally produced in industrial processes which do not produce pure substances; often impurities are introduced to the end product. An isomer is a compound with the same chemical composition as another compound but a different chemical structure.  In the PFAS world the terms “branched” and “linear” refer to differing isomers. As a short hand, people often mean all isomers of a particular compound when they name it. PFAS can also be cyclic in which case the linear/branched nomenclature breaks down.

Linear and branched non-polymeric PFAS are typically composed of two parts: a hydrophobic as well as lipophobic fluorinated carbon backbone and a typically polar hydrophilic functional group.  The suffix philic means an affinity for and phobic means fear or aversion, the prefix hydro means water and lipo is for lipid or fat. 

Structural analogues are compounds similar to other compounds but differing in one aspect. Structural analogues are also known as congeners. An example could be homologues. PFAS with the same functional groups differing in the number of carbons and fluorine atoms in the backbone are known as homologue series. For example, perfluoroalkyl carboxylic acids with 4 fully saturated carbons in the backbone to 12 fully saturated carbons in the backbone would form a homologue series.  A homologue group includes all linear and branched carboxylic acids with the same number of carbons in the backbone. For example, the C8 carboxylic homologue group includes linear perfluoroalkyloctanoic acid (PFOA), isopropyl-PFOA, and 3-methyl-PFOA; there are 89 total theoretically possible C8 carboxylic homologue congeners although in addition to the linear form. The picture below shows some C8 carboxylic homologue congeners, while technically separate compounds for ease they are often referred to as a singular entity.

Examples of branched PFOA
Image courtesy of Battelle Memorial Institute particularly Craig Hutchings and Steve Helgen. While technically different compounds these are often considered together.

Naming Systems

There are 5 main systematic methods currently in use to name fluorinated compounds: the International Union for Pure and Applied Chemistry (IUPAC) nomenclature, the perfluoro nomenclature, code numbers, Chemical Abstract Service (CAS) nomenclature, and F-nomenclature systems. Due to strong similarities, fluorinated organic compounds tend to follow hydrocarbon naming conventions.

Basic Conventions

Many PFAS are acids and may exist as a protonated or anionic form as well as a mixture of both depending on the pH. The pKa values tend to be quite small and scientists generally refer to PFAS with acid functionalities as “acids” rather than carboxylates, sulfonates, or the correct terms even though the dissociated forms may be the only relevant forms. Scientists refer to both the protonated and ionized forms by the same acronyms.  Most perfluorinated acids are environmentally anions.  Some labs report results in the acidic form, some report anions, and some a mixture.  Many times, perfluorinated carboxylic acids are reported as acids (for example perfluorooctanoic acid instead of perfluorooctanoate) and perfluoroalkyl sulfonic acids as anions (for example perfluorooctane sulfonate instead of perfluorooctane sulfonic acid).  This has caused confusion.  The labs are really measuring the concentration of perfluorinated acid anions present; when the lab reports an acid the lab adjusts for the cation. Most sulfonate standards are prepared from salts and the mass adjusted which is why they are often reported that way.  This is especially true for PFHxS, PFOS, ADONA, 9Cl-PF3ONS and 11Cl-PF3OUdS. Section 7.2.3 of EPA Method 537.1 details how to convert to adjust for this.

IUPAC Nomenclature

IUPAC Nomenclature systematically establishes unambiguous, unique, uniform, and consistent compound names based on their chemical structure.  IUPAC Nomenclature can be used for all organic compounds and is not specific to PFAS.  IUPAC Nomenclature is quite literally a book containing many precedents and steps however, the general simplified steps for IUPAC Nomenclature are:

  1. Identify the longest carbon chain.  The longest carbon chain is also known as the “parent chain.”
  2. Identify any groups off the parent chain.
  3. Number the carbons in the parent chain so that the groups off the parent chain have the lowest number.
  4. Number and name the groups just counted.
  5. Put all the name components together in alphabetical order; prefixes such as di- are not used for alphabetical order.

For example, C2F4 is tetrafluoroethene, shown below, is the simplest perfluorinated alkene (fully saturated carbon backbone with no functional groups).

Tetrafluoroethene
Picture from Wikidata. There are two carbons and a double bond so it is named “ethene.” Tetrafluoro comes from the 4 fluorine atoms attached to the carbons.

Perfluoro Nomenclature

Perfluoro Nomenclature only applied to perfluoroalkyl substances.  It is commonly used to quickly identify fully fluorine saturated carbon compounds. For shorter substances using IUPAC naming conventions is still easy and understandable. Most chemists would immediately understand that hexafluorobenzene (C6F6 – shown below) has a cyclic fully saturated carbon backbone. However, for longer compounds such as pentadecafluorooctanoic acid it is difficult to readily tell which is the motivation for Perfluoro Nomenclature.  The proper IUPAC name for that compound is actually: 2,2,3,3,4,4,5,5,6,6,7,7,8,8,8-pentadecafluorooctanoic acid which is fairly cumbersome to use further motivating Perfluoro Nomenclature.  The pentadecafluoro refers to the 15 fluorine atoms, octanoic acid refers to a carboxylic acid functional group that is off the 8th carbon in a chain.  This compound is pictured under hexafluorobenzene.

Hexafluorobenzene
Picture from Wikimedia. Hexafluoro denotes the 6 fluorine atoms coming off the carbons in the benzine ring. By Buck et al’s or one of the OECD’s PFAS definitions this compound would not be included however, it would be under Glüge et al’s definition. The preferred IUPAC name for this compound is 1,2,3,4,5,6-hexafluorobenzene.
Pentadecafluorooctanoic acid
Pentadecafluorooctanoic acid courtesy of PubChem.

Perfluoro Nomenclature uses the prefix perfluoro along with standard hydrocarbon nomenclature. This simplified naming system has been in place since the 1950s and is the most common naming system among practitioners. The acronyms developed from this system follow a simple pattern; they all start with the prefix PF for perfluoro then have a root based on the carbon backbone, and a suffix denoting the functional group.  The table below gives the roots for C1-C14 and the two most common functional group abbreviations are A for carboxylic acids as well as S for sulfonic acids.

Carbon backbone length naming roots
Table of roots for specific carbon backbone lengths.
Carboxylic and sulfonic functional groups
The carboxylic acid (left) and sulfonic acid (right) functional groups. The R represents some organic chain.

The acronym itself provides a well-defined structure for the PFAS compound.  For instance perfluorobutanesulfonic acid or PFBS is shown below.  The front letters PF stand for per-fluoroalkyl, the B stands for but-, -ane shows there are only single bonds in the carbon backbone which is implied, and the S is for sulfonic acid.  PFBA, PFHpA, and PFDA are also shown.

Perfluorobutanesulfonic acid or PFBS
Perfluorobutanesulfonic acid or PFBS. The sulfonic acid functional group is circled in dashed yellow, the carbons are in red, numbered so that the first carbon is nearest the functional group. By convention, the unlabeled connectors are carbon atoms. Carbon always forms 4 total bonds, if 4 bonds are not shown the carbon by general agreement is bonded to a hydrogen.
Examples of PFAS acronyms
The table shows the appropriate root color coded, carboxylic acid groups are circled in dashed blue and sulfonic acid groups are circled in dashed yellow. PFBS is perfluorobutanesulfonic acid, PFHpA is perfluoroheptanoic acid, and PFDA is perfluorodecanoic acid. PFBA is perfluorobutanoic acid however, butanoic is sometimes replaced by butyric acid in older works.

Should it be necessary to refer to a specific salt for a perfluorinated compound it is customary to write the salt’s common abbreviation in front of the standard perfluorinated abbreviation then drop the acid from the name.  For instance, the ammonium salt of PFOA, ammonium perfluorooctanoate, is often abbreviated APFO. While not strictly included in the perfluorinated system, some polyfluoroalkyl compounds can degrade into perfluorinated compounds. A polyfluoroalkyl compound is one where the carbon backbone is not fully fluorinated. An important subset of polyfluoroalkyl substances are fluorotelomers. Fluorotelomers are substances made from the most common industrial process for perfluorinated compounds, telomerization. In telomerization a transfer agent, known as a telogen, reacts with a polymerizable taxogen (monomer) to produce a telomer.  Generally in commercial production, perfluoroethyl (pentafluoroethyl) iodide as a telogen reacts with tetrafluoroethylene oligomers as taxogens, most commonly tetrafluoroethylene, to produce telomer perfluoroalkyl iodide polymers.  The perfluoroalkyl iodide polymers are then converted into other substances.

Fluorotelomers
Picture from the Big Chemical Encyclopedia showing pentafluoroethyl iodide reacting with tetrafluoroethylene oligomers to produce perfluoroalkyl iodide polymers.

Similar to perfluorinated acids, fluorotelomer substances are typically named for their functional group.  Fluorotelomers often are abbreviated FT followed by their functional group.  There are often numbers preceding the abbreviation such as 8:2. The first number represents the total perfluorinated carbon atoms and the second number the unsaturated carbons atoms.

8:2 FTOH
By convention the unlabeled connectors are carbon atoms. Carbon atoms always have 4 bounds and as this field was developed from hydrocarbon chemistry the hydrogens are typically not shown unless part of a functional group. The carbon atom labeled “2” in green for instance has two hydrogens attached to it. An alcohol group is a hydroxyl connected to an aliphatic carbon.

Code numbers

Systematic names are fantastic in precision but can be difficult to use.  Unless you work with compounds frequently, memorizing the prefix structures and extra rules, which were glossed over in this article can represent an annoying time commitment.  Additionally, it can be error prone especially to infrequent or new users.  Industrial PFAS manufacturers such as ICI Fluoropolymers, ISC, DuPont, and 3M developed inhouse shorthands for PFAS.  As the inhouse systems were not meant for the general public this initially caused confusion. In Organofluorine Chemistry dichlorodifluoromethane (CF2Cl2) is used as an example to illustrate this. Dichlorodifluoromethane was known as Freon-12 by DuPont, Arcton-6 by ICI, and Isceon-122 by ISC. By 1957 a standardized code number system based on DuPont’s system was adopted and formalized as The American Society of Heating, Refrigerating and Air-Conditioning Engineers (ASHRAE) Standard 34 which was last updated in 2019. DuPont’s system was first developed by Albert Henne, Thomas Midgley, and Robert McNary in 1929.

Freon-12

Dichlorodifluoromethane (CF2Cl2), better known as Freon-12, was formerly a popular chlorofluorocarbon halomethane refrigerant now banned under the Montreal Protocol. It is now only allowed as a fire suppressant in submarines and aircraft. Picture from the Gas Encyclopedia by Air Liquide.

In the ASHRAE system for pure compounds, a letter designates the primary purpose of the compound, R for refrigerant, P for aerosol propellant, S for solvent, and the numbers are based on the chemical formula.  Sometimes the letter is replaced with a  trade name such as Freon.  For blends, numbers are assigned sequentially based on ASHRAE data review completion date. For an ASHRAE designation, the first digit from the right is the number of fluorine atoms.  The second digit from the right is the number of hydrogen atoms plus one.  The third digit is the number of carbon atoms minus one; if this is a zero then that number would be omitted. The fourth digit is the number of unsaturated carbon-carbon bonds, in saturated compounds this number is omitted. If an upper-case B or I appears the number immediately following it is the number of bromine or iodine atoms respectively. There are often lowercase letters following the numeric designations.  The first appended letter is for substitutions on the central carbon atom, an x represents a chlorine substitution, y for fluorine, and z for hydrogen. The second appended letter designates substitutions on the terminal methylene carbon, =CCl2 is -a, =CClF is -b, =CF2 is -c, =CHCl is -d, =CHF is -e, and =CH2 is -f. Isomers are also designated by a Z or an E appended to the name for “zusammen” or “entgegen” respectively. Zusammen is German for together and entgegen is opposite; they represent cis and trans isomers respectively. 

Cyclic compounds (R300 series), ethers, inorganic fluids (R700 series), and miscellaneous organic compounds (R600 series) have additional rules.  The series are specified so the 000 series are methane based compounds, 100 are ethane based, 200 are propane based, and 300 are cyclic. The 400 series are zeotropes and 500 are azeotropes. The 600 series are other organic compounds. The 700 series are inorganic refrigerants such as ammonia, also known as R-717. The 1000 series which are unsaturated organic compounds such as the new R-1234yf refrigerant. R-1234yf is used for about half of all automobiles built after 2018 and it breaks down into short chained perfluorinated carboxylic acids; specifically, trifluoroacetic acid.

R-1234yf
2,3,3,3-Tetrafluoropropene also known as HFO-1234yf and R-1234yf.  It has a greenhouse gas (GHG) warming potential less than that of carbon dioxide. R-134a, which R-1234yf  helped replace, has a GHG warming potential of 1,430 as a comparison. Picture from Wikipedia.
The compound on the left is R-1234ye(E) and the compound on the right is R-1234ye(Z).
The compound on the left is R-1234ye(E) and the compound on the right is R-1234ye(Z).  The part which makes the compound an isomer is circled in dotted blue lines. R-1234 has other possibilities and chemical structures as well which can be further specified by the letters following the numbers. As an example R-1234yc is CH2FCF=CF2.

There are other code systems in use that are more field dependent as well.  For instance, chlorofluorocarbons have a numbering system as do halogenated fire extinguishers.  The Halon numbering system is in comparison very easy; there are always four numbers and left to right the digits represent carbon, fluorine, chlorine, and bromine atoms present in the molecule.  For instance, Halon-1211 (CF2ClBr also known as Freon-12B1) and Halon-1301 (CF3Br which would also be known as R-13B1).  On 1 January 1994 the United States banned the import and production of halons 1211 and 1301 under the Clean Air Act to comply with the Montreal Protocol. These halons are still allowed to be used and recycled halons may be purchased.  Both Halon 1211 and 1301 have Class A, B, and C ratings. Halon-1211 is a “streaming agent,” and more commonly used in hand-held extinguishers because it discharges mostly as a liquid stream.  Halon-1301 is a “flooding agent” and discharges mostly as a gas, allowing it to penetrate tight spaces and behind obstacles making it ideal for enclosed spaces commonly found in aircraft.  The United States owns about 40% of global halon-1301 supply and it will likely stay in use for many years worldwide.  Halon-1301 is critical as it was formerly the only material usable in enclosed spaces where humans were present. 

CAS nomenclature

CAS stands for Chemical Abstract Service (CAS) and it is a division of the American Chemical Society. A CAS number is a unique identifier assigned by CAS to every chemical substance. It includes isotopes, mixtures, alloys, and substances which have unknown or variable composition. CAS numbers do not contain information about the substance structure unlike all previously discussed naming systems, simplified molecular-input line-entry system (SMILES), or the IUPAC International Chemical Identifier (InChI) system.

The same PFAS chemical in different forms will have differing chemical properties because of structural differences.  For example, PFOS (perfluorooctanesulfonic acid) in its acid form (C8HF17O3S) has a CAS number of 1763-23-1, its potassium salt (C8F17KO3S) 2795-39-3, and its ammonium salt (C8H4F17NO3S) 29081-56-9.

F-Nomenclature

F-nomenclature was accepted by the American Chemical Society as an alternative to perfluoro nomenclature because some early fluorochemistry pioneers disliked perfluoro nomenclature. JH Simons in particular disliked perfluoro nomenclature. Simons invented the electrochemical fluoridization processes which was the first industrial process for producing perfluorinated compounds.

In F-nomenclature perfluoropentanoic acid (PFPeA – a C5 fully saturated carboxylic acid) would be F-pentanoic acid. As an aside, C5H10O2 which is pentanoic acid, is also known as valeric acid because it is the cause of the unpleasant smell in valerian.

Valerian
Picture of valerian by Ivar Leidus.  The unpleasant smell these flowers give off is caused by pentaonic acid.

Some elements of this naming system have survived.  For instance, the symbol -R which indicates an organic backbone sometimes is written -RF to indicate a perfluoro backbone. Also, placing an F internal to a benzene ring structure is a shorthand saying that all the bonds off the ring not otherwise indicated are fluorine instead of hydrogen.  A forerunner to F-nomenclature used a phi (φ) but was generally similar to F-nomenclature. 

Other less common nomenclature systems

In the 1970s, J.H. Simons, an early fluorochemistry pioneer, advocated for placing “for” before the final syllable in standard hydrocarbon nomenclature to convey it was perfluorinated. Organofluorine Chemistry gives the following examples: CF4 as methforane and the perfluorinated version of ethene, CF2=CF2 would be ethforene. 

Conclusion and Key Take Aways

Most PFAS naming systems are designed to reveal information about the basic chemical structure or function and to facilitate communication.  In industrial settings where not many PFAS are used simultaneously it can be easier to use codes to cut down on potential errors common in systematic names.  It is important to understand the basic names within your specific use.

This article is one of several on PFAS. You can read about PFAS discovery, structure, or all my articles on PFAS.

References

PFAS Structure

Common PFAS uses
This image shows some common uses of PFAS. Image courtesy of Carollo Engineers; particularly Cayla Cook and Eva Steinle-Darling.

Per- and polyfluoroalkyl substances (PFAS) are a ubiquitous emerging public health threat. PFAS terminology can be extremely confusing because it looks like an alphabet soup of similar acronyms. This article is the first of two on PFAS terminology. This one intends to provide an overview of PFAS structure, the second one intends to help demystify PFAS terminology and nomenclature. My previous article on PFAS was on Dr. Roy Plunkett’s discovery of PTFE, a tetrafluoroethylene fluoropolymer.

Scope

The EPA’s comptox database lists over 9,252 PFAS; this is too large a class to name on individual bases. A systematic naming convention has evolved so that much information is conveyed with just the name. There are 5 main ways to name fluorinated compounds: the perfluoro nomenclature, F-nomenclature, code numbers, the International Union for Pure and Applied Chemistry (IUPAC) nomenclature, and Chemical Abstract Service (CAS) nomenclature systems. Additionally, fluorine chemistry as a field has existed long before those five systems were created and naming was not really standardized until Buck et al tried to harmonize conventions in 2011. The idea of this article is to provide an overview of common PFAS groupings, the second article will go into the five naming conventions.

Introduction

PFAS is a general nonspecific name encompassing a group of substances.  There is no clear agreed upon definition of what exactly counts as PFAS.  The Organization of Economically Developed Countries (OECD), the United States Environmental Protection Agency (EPA), and the World Health Organization (WHO) have all used various definitions.  In the paper meant to harmonize conventions, Buck defined PFAS as “highly fluorinated aliphatic substances that contain 1 or more carbon atoms on which all the hydrogen substituents (present in the nonfluorinated analogues from which they are notionally derived) have been replaced by F atoms, in such a manner that they contain the perfluoroalkyl moiety CnF2n+1–.” This definition was the first clear PFAS definition. A moiety means part of a molecule. The OECD/United Nations Environment Program (UNEP) pointed out that Buck’s definition left out many substances commonly recognized as PFAS such as perfluorodicarboxylic acids and recommended the –CnF2n– moiety instead, although there is still debate surrounding this. Buck’s definition was updated by Glüge et al and informed the OECD/UNEP definition.  Glüge’s definition expands Buck’s to cover perfluorocarbon chains with functional groups on both ends, aromatic substances with perfluoroalkyl moieties on side chains, and fluorinated cycloaliphatic substances.

Historical Note

As mentioned in the PFAS discovery article, PFAS were initially investigated to replace sulfur dioxide, methyl chloride, ammonia, and other extremely dangerous early refrigerants. This may jog your memory; the first major public PFAS concerns were mainly focused on perfluorocarbons under the 1987 Montreal and 1997 Kyoto Protocols.  The Montreal Protocol aimed to limit chlorofluorocarbons.  The Kyoto Protocol aimed to limit 7 greenhouse gas (GHG) categories and stated that climate change is real and driven by anthropogenic emissions. The GHG categories included perfluorocarbons (PFCs) and hydrofluorocarbons (HFCs).

Kyoto Protocol countries by agreement status
Photo courtesy of Wikimedia Commons Green: Annex B parties with binding targets in the second period, Purple: Annex B parties with binding targets in the first period but not the second, Blue: non-Annex B parties without binding targets, Yellow: Annex B parties with binding targets in the first period but which withdrew from the Protocol, Orange: Signatories to the Protocol that have not ratified, Red: Other UN member states and observers that are not party to the Protocol.

Unfortunately, early 2000 environmental scientists adopted the PFC acronym for PFAS instead of the perfluorocarbons identified in the Kyoto Protocol. There is still quite some confusion caused by this. While PFC is used in turn of the millennium PFAS literature it should be avoided now.

General Organofluorine Concepts

Carbon (C) bonded to fluorine (F) is the class basis for PFAS.  The C-F bond is extremely persistent and the key factor for the problems PFAS causes as well as its desirable technical properties. Carbon can form up to 4 bonds with other atoms.  The first broad distinction is between polymers and non-polymers. A polymer is a molecule made up of repeating subunits called monomers. Polymers often serve as the feedstock to produce other PFAS chemicals, the most widely recognized fluoropolymer is polytetrafluoroethylene (PTFE) which Dr. Roy Plunkett discovered on 6 April 1938.

Structure of PTFE repeating monomer
Picture courtesy of Wikipedia Commons. This depicts PTFE. The brackets show the monomer tetrafluoroethylene, the n symbolizes that this is a repeating structure.

Functional groups often serve as the basis for classification systems. A functional group is a moiety made of a specific structure which causes characteristic chemical reactions which are similar no matter what the rest of the molecular composition is. PFAS chemicals can also exist in multiple states such as acids, anions, cations, and salts which have important implications for their physical and chemical properties. Anionic forms are the environmentally prevalent form and the general form most authors refer to. Some legislation, particularly European Registration, Evaluation, Authorisation, and Restriction of Chemicals (REACH), defines substance to include impurities and stabilizers of the main PFAS compound.

Broad non-polymeric structure

Non-polymeric PFAS include perfluorinated and polyfluorinated substances.  When carbon is bound only to fluorine except for functional groups it is called perfluorinated and the compound is saturated with F. When some carbon bonds include things other than functional groups or fluorine it is called polyfluorinated and is considered unsaturated with respect to F; hydrogen is the most common other bond. As PFAS stands for “per- and polyfluoroalkyl substances” and no single compound can be both unsaturated and saturated with respect to fluorine simultaneously “PFAS” is by default a plural acronym.  Both per- and poly-fluoroalkyl substances are subdivided into classes where the functional groups behave relatively similarly.  Two large classes are fluoroalkyl acids and fluoroalkane sulfonamides. These large classes are then subdivided again based on functional groups/moieties.  For example, perfluoroalkyl acids are further subdivided into carboxylic, sulfonic, sulfinic, phosphoric, phosphinic, and other acid types.  There are about 425 common moiety-based subdivisions within PFAS.

PFAS categorizations
Picture courtesy of The Interstate Technology Regulatory Council. This photo goes over some broad PFAS categories; while only 5 moiety based groups are shown here there are currently over 425 acknowledged nonpolymer moiety classification groups.

In 2017, Wang et al published an iconic chart covering the number of papers published on various PFAS groups reproduced below.

Number of peer reviewed articles between 2002 and 2016 for various PFAS.
Picture from Wang et al. This shows some broad helpful PFAS classifications. PFCA stands for perfluorinated carboxylic acids, PFSA for perfluorinated sulfonic acids, PFPA for perfluorinated phosphoric acids, PFPiA for perfluorinated phosphinic acids, PFECA for perfluoropolyether carboxylic acids, PFESA for perfluoropolyether sulfonic acids, and PASF for perfluoroalkane sulfonyl fluorides. Examples of groups left off this classification include perfluoroalkyl iodides (PFAI) and many others. The articles mentioned cover 2002 to 2016.

Conclusion and Key Take Aways

There is no clear definition on what PFAS encompass, even within regulatory organizations. There are about 9,252 PFAS substances which are broadly divided into polymeric and non-polymeric substances.  Non-polymeric PFAS subclasses are based on carbon chain saturation with fluorine into full saturated (perfluoroalkyl) or non-fully saturated (polyfluoroalkyl) groups. Those groups are subdivided based on moieties/functional groups so that compounds which behave similarly are classified together. An upcoming article will cover the five common classification systems for individual compounds.

Other articles in the series include PFAS Discovery

Further Reading on PFAS classifications

PFAS Discovery

Reenactment of the 1938 discovery of Teflon. Left to right: Jack Rebok, Robert McHarness, and Roy Plunkett
Reenactment of the 1938 discovery of Teflon. Left to right: Jack Rebok, Robert McHarness, and Roy Plunkett Photo courtesy of Hagley Museum and Library

Per- and polyfluoroalkyl substances (PFAS) are a widely used class of chemicals. You’re probably familiar with some of the popular brand names employing these chemicals such as Teflon, Gortex, and Dockers Stain Defender. As our understanding of PFAS has evolved it is becoming an emergent public health threat. This article is the first in a series serving to provide information on PFAS and it will cover their discovery. Other articles in the series will cover concern, regulation, treatment, environmental fate, contaminated sites, consumer protection, uses and provide sources for further information.

Introduction

Per- and polyfluoroalkyls substances (PFAS) are a family of synthetic substances covering over 4,700 chemicals which have a number of deleterious health effects attributed to them. As of 7 June 2020 California, Connecticut, Colorado, Minnesota, North Carolina, New Hampshire, New Jersey, and Vermont all have state health guidelines for some PFAS. New Jersey’s limits just recently started on 1 June 2020. The US Environmental Protection Agency (EPA) has established a health advisory of 70 parts per trillion of combined PFAS.  While PFAS is not directly regulated under the Toxic Substances Control Act (TSCA) it is monitored under the Significant New Use Rule (SNUR). On 20 February 2020 the EPA proposed a supplemental SNUR for PFAS.

Like most things, an exact beginning is hard to quantify. PFAS’ story could start in a letter dated 26 August 1812 when André-Marie Ampère wrote to Humphry Davy postulating the existence of fluorine, or in 1869 when Dmitri Mendelvee positioned fluorine in the periodic table. An equally rational choice would be 1886 when Henri Moissan first isolated elemental fluorine in France leading to his award of the 1906 Nobel Prize in chemistry. Another serious contender would be Thomas Midgley and A. L. Henne’s 1928 invention of Freon and other chlorofluorocarbons (CFCs) in their Fridgidaire laboratory, which at the time was a General Motor’s subsidiary. I am choosing to start PFAS’ story with Roy Plunkett’s 1938 discovery of Teflon and the birth of fluoropolymers.  

Discovery

On 6 April 1938 at the Chemours Jackson Laboratory in New Jersey Dr. Roy Plunkett discovered polytetrafluoroethylene (PTFE) by accident while researching new CFC refrigerants. While CFCs are now banned for their deleterious atmospheric effects under the Montreal Protocol, at the time they were used to replace ammonia and sulfur dioxide refrigerants which killed dozens of workers annually. PTFE is better known by its brand name: Teflon. Although CFCs are perfluorinated compounds, PTFE was the first discovered chemical in the class of Per- and polyfluoroalkyl substances.

After work on 5 April 1938, Dr. Plunkett and his assistant Jack Rebok reacted tetrafluoroethylene (TFE) with hydrochloric acid then compressed the mixture into metal cylinders and froze it overnight. The next morning on the 6th of April, Jack Rebok placed one of the cylinders onto a balance then opened the stop valve. Only 990 grams of TFE came out of a supposedly 1 kg container. Puzzled by the mass balance, Dr. Plunkett tipped the cylinder over and a white powder fell out. Then Dr. Plunkett stuck a metal wire to try and get more of the substance out. He was unable to get much out that way so eventually Jack Rebok suggested to cut the flask open.

Photo of lab notebook page where Plunkett recorded the discovery of PTFE
Photo of lab notebook page where Plunkett recorded the discovery of PTFE from Kinnane, A. (2002). DuPont: From the banks of the Brandywine to miracles of science.

In Dr. Plunkett’s article The History of Polytetrafluoroethylene: Discovery and Development he wrote:

On the morning of April 6, 1938, Jack Rebok, my assistant, selected one of the TFE (tetrafluoroethylene) cylinders that we had been using the previous day and set up the apparatus ready to go. When he opened the valve — to let the TFE gas flow under its own pressure from the cylinder — nothing happened…We were in a quandary. I couldn’t think of anything else to do under the circumstances, so we unscrewed the valve from the cylinder. By this time it was pretty clear that there wasn’t any gas left. I carefully tipped the cylinder upside down, and out came a whitish powder down onto the lab bench. We scraped around some with the wire inside the cylinder…to get some more of the powder. What I got out that way certainly didn’t add up, so I knew there must be more, inside. Finally…we decided to cut open the cylinder. When we did, we found more of the powder packed onto the bottom and lower sides of the cylinder.

Instead of ignoring the powder Dr. Plunkett started experimenting on it and discovered PTFE is highly resistant to corrosive acids, has excellent performance in extreme temperatures, and does not dissolve in solvents. This along with its slippery nature lead to DuPont sending PTFE to its central research department. However, no real commercially viable use was found for PTFE.

Ironically, World War II saved Teflon from oblivion. On its own PTFE, what Dr. Plunkett discovered, is a relatively useless polymer. It melts at around 327°C (≈620°F) and under that temperature sits in a ball of nonflowing gel. PTFE does not dissolve in anything and does not react with acids, bases, or solvents and at the time cost about $100 per pound (about $1,820 per pound or $4.02 per gram in 2020 dollars) to manufacture.

The Manhattan Project was the US effort to develop the atomic bomb and the savior of PTFE. The Manhattan Project needed corrosion resistant materials to separate U-235 from U-238 using differential diffusion of UF6. After Lieutenant General Leslie Groves heard of PTFE’s inertness, he verified it could separate U-235 from U-238. Then following LTG Groves’ request, the US Patent Office placed PTFE under a “Secrecy Order” and it was referred to only as “K-416.” Following military interest, DuPont patented PTFE in 1941 and registered the trade name Teflon in 1944.  The secrecy order lasted until 1946; by that time the Manhattan Project had paid for a great deal of research that otherwise would not have been carried out on the polymer and its manufacturing cost dropped tremendously.

Dr. Plunkett is also famous for leading DuPont’s team which added tetraethyllead (CH3CH2)4Pb to gasoline (which was phased out under the Clean Air Act) and for significant improvements to freon (a CFC refrigerant).

Brief PFAS Use Examples

The examples of PFAS extend across all facets of human life, from everyday household cookware to aerospace and electronics. PFAS’ widespread use takes advantage of its beneficial properties: chemical resistance, thermal stability, cryogenic properties, low friction coefficients, low surface energies, low dielectric constants, high volume and surface resistivities, and flame resistance. Once it was used to separate U-235 from U-238, the Manhattan Project immediately started finding other uses for PTFE. For example, PTFE was also used in the Manhattan Project in the antenna cap of proximity fuses thanks to its electrical insulating property and invisibility to Doppler radar. Fuel tank coatings used PTFE because of its resistance to low temperatures. After World War II, Teflon was turned to human well-being and started being used in catheters because of its low friction coefficient. PTFE was also used as insulation for wires and cables. It was even used during the Statue of Liberty’s renovations.  PTFE often serves as a precursor for other PFAS chemicals which were ubiquitous until their dangers were realized. PFAS are used in fire fighting foams, ski wax, stain-resistant materials (rugs, clothing, furniture, sprayable stain protectors), cookware, outdoor gear, cosmetics, shaving cream, sunscreen, shampoo, and myriad other applications.

Conclusion

While it may seem easy to villainize Dr. Plunkett for his discovery’s degradation of the environment and damage to human health it is critical to remember Dr. Plunkett in the context of this time. Early refrigerants included sulfur dioxide and ammonia; both regularly poisoned people. His contributions to tetraethyllead boosted octane levels enabling, among other things, advanced plane flight and jets. His work introduced numerous new products and processes which are widely used in medicine, refrigeration, aerosol, electronic, plastics, and aerospace. Several of his innovations are of critical importance to national defense.  There was also less awareness of the dangers of persistent chemicals to humans and the environment.

Further References

The EPA has designated Lahne Mattas-Curry as a point of contact and can be reached at mattas-curry.lahne@epa.gov

For more on the history and discovery of PFAS:

Other articles in the series include PFAS Structure

The EPA’s PFAS website is https://www.epa.gov/pfas

The EPA Long-Chain Perfluoroalkyl Carboxylate and Perfluoroalkyl Sulfonate Chemical Substances; Significant New Use Rule; Supplemental Proposal

PFAS SNUR on regulations.gov

NJ’s new PFAS rule

PFASproject.com – a group of faculty, post-doctoral scholars, graduate students, and undergraduates affiliated with the Social Science Environmental Health Research Institute at Northeastern University operating on an NSF grant