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What the American Academy of Pediatrics Report Got Wrong About PFAS in Food Packaging

The American Academy of Pediatrics (AAP’s) recently published a flawed technical report, “Food Additives and Child Health, that has created unwarranted concern about perfluoroalkyl chemicals (PFCs) in food packaging.[1]  It is important to set the record straight and address some of the problems with the report.

Before detailing specific concerns about the Report, however, it may be helpful to provide a brief background on the Food and Drug Administration’s (FDA) regulation of food contact substances, which includes substances used in food packaging.[2]

Before a new food contact substance can be sold or distributed in the US, it is reviewed by FDA through the submission of a Food Contact Notification (FCN).[3]  The FCN must contain data and information regarding:

  1. The chemical composition of the food contact substance, including all impurities and potential degradation products;
  2. The levels at which the food contact substance or any impurities or degradation products may be released from the food packaging under the intended use conditions and the resulting potential dietary concentrations of those substances; and
  3. Toxicity data (and any other relevant health and safety data) on the substance itself, and on all impurities, degradation products and other components of the food contact substance.[4]

FDA will allow the proposed food contact substance to be placed on the market only if the agency concludes, on the basis of the information contained in the FCN, that there is sufficient scientific data to demonstrate that the substance is safe for its intended use.[5]  If FDA makes such a determination, the food contact substance is allowed to be used as specified in the FCN and is added to FDA’s inventory of effective FCNs.[6]  After a food contact substance is added to that inventory, FDA maintains the authority to withdraw its acceptance of the substance at any time if available data no longer support the conclusion the food contact substance is safe for its intended use.[7]

One of the most striking flaws in the AAP report is that none of the PFC substances discussed in the report are authorized for use in food packaging in the US, as reflected on FDA’s inventory of effective FCNs.  Indeed, a careful review of the inventory shows that the specific PFC substances that are permitted for use in food packaging (and that are actually used in food packaging) in the US do not include, and are not anticipated to degrade to, any of the PFC substances discussed in the report, almost all of which were long chain:[8]

  • Perfluorohexane sulfonic acid (PFHxS);
  • Perfluorobutane sulfonate (PFBS);
  • Perfluorononanoic acid (PFNA);
  • Perfluorooctanoic acid (PFOA); and
  • Perfluorooctane sulfonic acid (PFOS)).

However, instead of addressing the specific PFC compounds that are authorized for use in food packaging, the AAP report focuses on these long chain PFCs, that are no longer allowed to be used in food contact applications.[9]

The PFC compounds that are used to provide grease resistance in food packaging are large polymers that are not, themselves, bioavailable.  Because the polymers are not bioavailable, regulators around the globe generally assess and characterize the risks of these compounds by examining their ultimate degradation products (i.e., their alkyl acids and salts).  Thus, for example, the risks associated with eight-carbon (C8) long chain PFCs are assessed and characterized by examining the hazard characteristics of PFOA and PFOS (i.e., eight-carbon acids).  On the other hand, the PFCs that FDA has reviewed and permitted for use in food packaging today include those based on six-carbon (C6) non-sulfonated molecules and do not include C8 or other long chain PFCs.  Accordingly, the risks associated with such compounds are assessed and characterized by examining the non-sulfonated C6 acid – perfluorohexanoic acid (PFHxA).

A second significant flaw in AAP’s report is the statement that the potential health effects of currently allowed PFC compounds “have not [been] sufficiently evaluated.”[10]  However, as illustrated below, this is factually incorrect.  The C6 PFC compounds that are listed on the inventory of effective FCNs are supported by a robust body of data demonstrating that these materials are safe for their intended use.

The full suite of standard laboratory assays are available for PFHxA.  These include:

  1. A 2-year rodent cancer bioassay (Klaunig 2015);
  2. DNA mutation and genotoxicity in vitro assays (NTP 2018, Loveless 2009, Eriksen 2010);
  3. Chronic systemic toxicity rodent bioassay (Klaunig 2015);
  4. Reproductive/developmental rodent bioassays (Loveless 2009, Iwai 2014, Iwai et al. in submission);
  5. Sub-chronic systemic toxicity bioassays (Loveless 2009, Chengelis 2009, Iwai 2014);
  6. Analysis of endocrine disruption (Borghoff 2018);
  7. High-throughput molecular in vitro assays (EPA Tox21); and
  8. Toxicokinetic assays in rats, mice, microminipigs, monkeys and humans (many; examples include Chengelis 2009, Iwai 2014, Russell 2013, 2015, Nilsson 2010, 2013, Fujii 2014, Guruge 2015, Gannon 2011, 2016).

These studies demonstrate the following:

  • PFHxA does not exhibit carcinogenicity, mutagenicity, or genotoxicity. PFHxA is not an endocrine disruptor.  Sensitive endpoints in rodent studies include effects on liver, thyroid, kidney, and hematology.  PFHxA was not carcinogenic and has not exhibited any DNA mutation or genotoxic effects in several studies (NTP 2018, Klaunig 2015, Loveless 2009, Nobels 2010).  A comprehensive review of both in vitro and in vivo studies evaluating PFHxA activity across endocrine pathways shows that PFHxA is not bioactive in estrogen, androgen, aromatase, or thyroid receptor signaling pathways (Borghoff 2018).  Effects noted from high level exposure to PFHxA in subchronic and chronic noncancer rodent bioassays include liver, thyroid, kidney, and hematologic effects (Loveless 2009, Chengelis 2009, Iwai 2014), with the lowest no-observed-adverse-effect-level (NOAEL) of 30 mg/kg-day from the chronic rat study (Klaunig 2015).
  • PFHxA does not exhibit adverse effects on reproduction, and developmental effects are mixed and occur at higher doses than other endpoints (see above). PFHxA has not demonstrated any adverse reproductive effects in mice or rats; however, findings regarding some developmental endpoints are mixed.  PFHxA exposure did not cause any developmental effects in rats (Loveless 2009).  A mouse study indicated some potential developmental concerns due to low incidences of increased stillbirths, pup death at postnatal days 1 to 4, and effects on the eye (Iwai 2014).  However, when the full concurrent controls are included and when historical controls from the same mouse strain and lab are evaluated, the low incidence of stillbirths is shown to be unrelated to PFHxA exposure.  Due to the inconsistency between studies and the questionable biological and statistical significance of the mouse effects, it is unlikely that PFHxA is a developmental toxicant.  However, even if these developmental endpoints were considered, the NOAEL from the 2-year rodent bioassay referenced above is more sensitive (i.e., lower) and, therefore, would be protective of any potential developmental effects in a quantitative risk assessment.

These and other data demonstrate that there is a high margin of safety for human exposure to PFHxA, including infants and children, from all routes of exposure and from food contact materials in the U.S.  For example, ANSES, the French agency for food safety, environment, and labor, issued an expert evaluation on the chronic risks of PFHxA for the French General Directorate of Health.[11]  ANSES derived a toxicity value (or “reference dose” in U.S. terminology) for PFHxA based on kidney effects from the chronic rodent study referenced above (Klaunig 2015), which was deemed protective of all other potential health endpoints of concern.  Given the extremely quick elimination of PFHxA from all species tested, the agency applied the standard allometric scaling based on body weights to convert the rodent administered dose to the human equivalent dose.  This methodology has been shown to be appropriate for PFHxA specifically (Russell 2013).  The agency also applied standard uncertainty factors to account for variability in humans and a database uncertainty.  The final toxicity value (oral reference dose) derived by ANSES is 0.32 mg/kg-day.  This reference dose is 16,000 times higher (meaning safer) than that found for PFOA or PFOS, and is a factor of 13,300 times less than the expected exposure from food packaging materials, being fully protective of human and infant health.

As this brief survey of the published literature indicates, the Technical Report is incorrect in suggesting that there are insufficient data available on the PFC compounds that are currently used in food packaging.  In fact, there is a substantial body of data on the C6 PFC compounds that have been reviewed and accepted by FDA for use in food packaging.  These data firmly support the conclusion that currently-available C6 PFC food contact substances are safe for their intended use in food packaging and should not be equated with long chain C8 compounds.

FluoroCouncil[12] is a global organization representing the world’s leading manufacturers of products based on PFCs, better known as per- and polyfluoroalkyl substances (PFAS).  FluoroCouncil has a fundamental commitment to product stewardship and rigorous, science-based regulation, and, as part of its mission, addresses science and public policy issues related to PFAS.

FOOTNOTES:

[1]        Vol. 142, No. 2; August 2018 [hereinafter Report].

[2]        See 21 U.S.C. § 348 (Definition of “food contact substance” includes “any substance intended for use as a component of materials used in manufacturing, packing, packaging, transporting, or holding food . . .”).

[3]        According to FDA, the FCN is “the preferred process for authorizing” the use of a food contact substance, see 67 Fed. Reg. 35,724 (May 21, 2002), although it is not the exclusive mechanism by which a new food contact substance may be lawfully sold or distributed in the US.  Other mechanisms include Generally Recognized As Safe (GRAS) determinations and food additive petitions.  See generally https://www.fda.gov/Food/IngredientsPackagingLabeling/PackagingFCS/Notifications/ucm2006854.htm.

[4]        See 21 U.S.C. § 348(h)(1) ; 21 C.F.R. §170.100.  See also, FDA, Guidance for Industry Preparation of Premarket Submissions for Food Contact Substances: Chemistry Recommendations (December 2007); FDA, Guidance for Industry Preparation of Food Contact Notifications for Food Contact Substances: Toxicology Recommendations (April 2002).

[5]        See 21 U.S.C. § 348(h)(1).

[6]        The Inventory of Effective FCNs can be accessed at the following url: https://www.fda.gov/Food/IngredientsPackagingLabeling/PackagingFCS/Notifications/default.htm.

[7]        See 21 C.F.R. §170.105(a).

[8]        PFBS is the only short chain PFC discussed in the report.  However, PFHxS was erroneously described as a short chain in the Report.

[9]        As others have reported (see, e.g., Vedagiri UK, Anderson RH, Loso, HM, Schwach CM.  Ambient levels of PFOS and PFOA in Multiple Environmental Media. Remediation.  2018;28:9–51.), certain long chain PFAS compounds, including PFOA, are nearly ubiquitous in the environment.  Accordingly, it is possible that modern food packaging materials – including products containing current FDA-authorized PFC substances – may contain long chain PFC chemicals as impurities.  However, for packaging products made with current FDA-authorized PFC substances, long chain impurities would only be expected to be present at trace levels, if at all.

[10]      Report at 4.

[11]      https://www.anses.fr/fr/system/files/SUBSTANCES2015SA0127Ra.pdf.

[12]      FluoroCouncil’s member companies are Archroma Management LLC, AGC, Inc., Daikin Industries, Ltd., Solvay Specialty Polymers, The Chemours Company LLC, Dynax (associate), and Tyco Fire Products LP (associate).

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