FDA scientists push back on an industry-funded analysis about bioaccumulation and toxicity of short-chain PFAS

Tom Neltner, J.D.Chemicals Policy Director and Maricel Maffini, Ph.D., Consultant

Note to readers: As we all grapple with the grave global health challenge from COVID19, we want to acknowledge the essential services that professionals at the Food and Drug Administration (FDA) and in the food production, processing and retail industries provide in continuing to deliver food. In the meantime, we are continuing to work towards improved health protections – including reducing chemicals in food. We’ll plan to keep sharing developments that may be useful to you. In the meantime, please stay safe and healthy.

Last year, we reported on a sophisticated analysis performed by FDA’s scientists showing that 5:3 acid, a breakdown product of a short-chain PFAS known as 6:2 fluorotelomer (6:2 FTOH) was slow to be eliminated by the body. The authors concluded that the metabolite was an important biomarker for assessment of long-term exposure to 6:2 FTOH and showed potential bioaccumulative (aka biopersistence[1]) properties. The chemical 6:2 FTOH is a common starting substance in the manufacture of many PFAS polymers, including those used to greaseproof paper and paperboard. As a result, it is a major impurity in, and degradation product of, these polymers.

We are now reporting on two recent publications by the same group of FDA scientists (Kabadi et al.[2] and Rice et al.)[3] in which they not only confirmed their initial findings but also produced new evidence on the behavior of short-chain PFAS when they enter the body. The new evidence highlights:

  • Bioaccumulation: 6:2 FTOH is transformed by the body into several metabolites; one of them, called 5:3 acid, bioaccumulates, and the bioaccumulation is greater with lower exposure to 6:2 FTOH.
  • Toxicity: The toxicity of 6:2 FTOH is concerning and its risk to human health may have been significantly underestimated previously. Data on perfluorohexanoic acid (PFHxA), the industry’s proposed reference chemical for the short-chain PFAS class are not appropriate for assessing the potential health effects of 6:2 FTOH.

The FDA’s scientists reached these important conclusions after reviewing “recently received additional data on 6:2 FTOH and 5:3 acid” and more than a dozen reports on oral toxicity studies that “had been conducted and submitted by industry in support for food contact uses” of short-chain PFAS in addition to a study by the National Toxicology Program. They also called out flaws in industry-funded analyses that reached different conclusions.


FDA’s commitment to review its authorized PFAS uses in food packaging is showing results

The latest publications are likely the result of the agency’s ongoing review of the authorized uses of short-chain PFAS in food contact applications. The thorough analysis by FDA’s scientists comparing the toxicology databases for 6:2 FTOH and PFHxA “directly contradicts” conclusions published by consultants paid by industry that “PFHxA may also represent a suitable marker for safety of fluorotelomer replacement chemistry.”

In a previous blog and a Letter to the Editor, we called out the FluoroCouncil-funded publications for making overreaching statements unsubstantiated by the evidence while ignoring an earlier publication by FDA’s scientists describing, for the first time, the “high biopersistence potential of 6:2 FTOH.” Now, in their January 7, 2020 publication, Kabadi et al. have not only confirmed their initial analysis, but produced significant new information on how the body responds to consumption of 6:2 FTOH.

The authors performed a detailed review of a 90-day repeated-dosing oral 6:2 FTOH pharmacokinetic study performed by DuPont.[4] In the DuPont study, rats were administered 3,3,4,4,5,5,6,6,7,7,8,8,8-tridecafluorooctan-1-ol, the 6:2 FTOH used to make the food contact substance authorized under food contact notification (FCN) 940.[5] The DuPont study is dated 2012, two years after FDA authorized its use. Even though the study is more than seven years old, Kabadi et al. describe the study as “recently received,” suggesting that DuPont did not proactively share it with the agency.

In addition to characterizing the bioaccumulation of short-chain FTOH metabolite, Rice et al. performed a comparative analysis of toxicology data for 6:2 FTOH and perfluorohexanoic acid (PFHxA), a breakdown product of 6:2 FTOH touted by industry as “less hazardous to human health than PFOA” and a suitable marker for the “safety of fluorotelomer replacement chemistry.” The findings by FDA’s scientists could not be more different than industry’s. Compared to PFHxA[6], 6:2 FTOH:

  • Has higher mortality rates;
  • Is more toxic to the liver and kidney;
  • Causes developmental, reproductive and immune toxicity; and
  • Is more toxic during the postnatal period, with increased mortality in pups and decreased growth during lactation.

This critical comparative work demonstrates that “the dataset for PFHxA is not appropriate for assessing the potential human health effects associated with 6:2 FTOH exposure,” since the toxicological profile of 6:2 FTOH is much more concerning. FDA scientists concluded that applying safe exposure levels from toxicity studies conducted for PFHxA when performing “the human health risk assessment of 6:2 FTOH exposure may significantly underestimate the risk to human health.”