Comments on Availability of Draft Toxicological Profile: Perfluoroalkyls

Monday, August 20, 2018 - 5:15pm

CH A M B E R O F CO M M E R C E
O F T H E
UN I T E D ST A T E S O F AM E R I C A

1615 H ST R E E T, NW WA S H I N G T O N, DC 20062 ( 2 0 2 ) 463-5310

August 20, 2018

VIA ELECTRONIC FILING

Ms. Susan Ingber
Division of Toxicology and Human Health Sciences
Agency for Toxic Substances and Disease Registry
1600 Clifton Road, NE, MS F-58
Atlanta, GA 30329

RE: Availability of Draft Toxicological Profile: Perfluoroalkyls, 83 Fed. Reg. 28,849
(June 21, 2018); Docket No. ATSDR-2015-0004

Dear Ms. Ingber:

The U.S. Chamber of Commerce submits these comments regarding the Agency for Toxic
Substances and Disease Registry’s (“ATSDR” or “Agency”) 2018 draft toxicological profile (“Draft
Profile”) for perfluoroalkyls (“PFAS”).1 A number of Chamber members have produced PFAS in
the past and ATSDR’s Draft Profile would adversely affect them. It is imperative that Federal
agencies base their policies and actions regarding PFAS on the best available science and weight of
the scientific evidence.

I. Background

The Chamber and its members care profoundly about the health and safety of their
employees, customers, and the communities in which they live. PFAS are a group of synthetic
chemicals used in manufacturing and in consumer products. These chemicals are persistent in the
environment and are subject to growing interest and debate due to concerns about effects on human
health.

PFAS are typically found in food, commercial household products, drinking water, and the
workplace. Aqueous film forming foam (“AFFF”), a product used by the U.S. military, firefighters,
1 See Availability of Draft Toxicological Profile: Perfluoroalkyls, 83 Fed. Reg. 28,849 (June 21, 2018); Agency for Toxic
Substances and Disease Registry, Toxicological Profile for Perfluoroalkyls – Draft for Public Comment (June 2018), available at
https://www.atsdr.cdc.gov/toxprofiles/tp200.pdf (“Draft Profile”).

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August 20, 2018
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and airport safety professions because it was extremely effective in fighting fuel-fed fires, was the
most common use of PFAS.

Companies historically used the two most studied PFAS, perfluorooctanesulfonic acid
(“PFOS”) and perfluorooctanoic acid (“PFOA”), in these important applications. However,
beginning in the early 2000s, those same companies began to phase out the production of those and
other PFAs.2 Since then, there has been a significant decline in industrial releases of PFAS from
chemical facilities3 and a 70 – 80% decline in PFOS and PFOA levels in the U.S. population in the
same period.4 Clearly, regulators and the business community alike have taken the correct steps to
mitigate the impact of PFAS.

It is imperative that ATSDR’s Draft Profile uses the best available science, and the Chamber
believes that ATSDR can achieve this goal by withdrawing or revising the Draft Profile. The
Chamber and its members offer the following comments.

II. The Draft Profile Fails to Provide Stakeholders With an Adequate Perspective on the
Toxicology of PFAS

The Draft Profile fails to meet its “primary purpose” of providing “public health officials,
physicians, toxicologists” and others “with an overall perspective on the toxicology” of PFAS.5 The
Draft Profile relies on flaws and incomplete data that does not justify its conclusions. As a result,
ATSDR’s derivation of minimal risk levels (“MRLs”) is deeply flawed. These errors make any
reliance on ATSDR’s analysis and conclusions unwarranted, and they would render any agency
action that relies on the report “arbitrary and capricious” and subject to legal invalidation.

ATSDR must state that the MRLs neither define unsafe levels nor supply appropriate
regulatory standards. As ATSDR indicates, MRLs are “not intended to define clean up or action
levels” but rather are “intended only to serve as a screening tool.”6 ATSDR also states that an
“MRL may be as much as 100-fold below levels that have been shown to be nontoxic in laboratory
2 See, e.g., Perfluoroalkyl Sulfonates; Significant New Use Rule; Final Rule and Supplemental Proposed Rule, 67 Fed. Reg.
11,007, 11,010 (Mar. 11, 2002) (“3M committed to phase out these chemicals voluntarily by discontinuing their
manufacture on a global basis by the end of December 2000, and 3M has confirmed that these chemicals were
discontinued on schedule”).
3 See U.S. Environmental Protection Agency, EPA's Non-CBI Summary Tables for 2015 Company Progress Reports
(Feb. 2017), available at https://www.epa.gov/sites/production/files/2017-
02/documents/2016_pfoa_stewardship_summary_table_0.pdf.
4 Geary W. Olsen, et al., Per- and Polyfluoroalkyl Substances (PFAS) in American Red Cross Adult Blood Donors, 2000–
2015, 157 Envtl. Research 87–95 (2017) (Percentage declines 2000–2001 to 2015 were…88% (PFOS), and 77%
(PFOA)), available at https://www.sciencedirect.com/science/article/pii/S0013935117306916?via%....
5 Draft Profile at 21.
6 Id. at A-1.

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August 20, 2018
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animals.”7 The Agency admits, “if someone is exposed to an amount above the MRLs, it does not
mean that health problems will happen.”8

This is particularly true with the proposed MRLs for PFAS, as ATSDR admits that the
scientific evidence does not support causation in humans for any of the health effects that it examined,
observing that it has not established “cause-and-effect” relationships for any of the effects.9
ATSDR, however, buries this important concession deep in the Draft Profile.

While ATSDR briefly discusses the meaning of MRLs in Appendix A, it should instead
acknowledge these facts at the outset of the Draft Profile in section 1.2, the “Summary of Health
Effects.”10 Failing to provide clear and proper notice of these facts to affected stakeholders and
failing to do so misrepresents the science and misleads readers.

III. ATSDR’s MRLs for PFAS are Based on Flawed Studies of Limited Relevance to
Humans

ATSDR uses unreliable science to support unnecessarily low MRLs and should withdraw or
revise those levels to reflect a more realistic and scientifically supported risk assessment. Some of
the critical flaws in the derivation include the following:

First, ATSDR derives its MRLs from adverse effects observed in rodent studies, even
though their relevance to human health is questionable due to well-established differences between
human and rodent physiology. For PFOA and PFOS, ATSDR relies on developmental effects
purportedly seen in the offspring of mice and rats exposed to high levels of PFAS.

ATSDR acknowledges, however, “there is strong evidence that some effects observed in
rodents, such as…immunotoxicity, and developmental toxicity, involve the activation of the
peroxisome proliferator-activated receptor alpha (“PPARα”); however humans and non-human
primates are less responsive to PPARα agonists than rodents.”11 In fact, ATSDR does not consider
the particular developmental effects observed in these rodent studies (altered bone development and
neurological effects) to be associated with PFAS in humans at all.12

7 Id.
8 Agency for Toxic Substances and Disease Register, Minimum Risk Levels, available at
https://www.atsdr.cdc.gov/minimalrisklevels/index.html.
9 Draft Profile at 636.
10 Id. at 4.
11 Id.
12 Id. at 141-145; 293-296.

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August 20, 2018
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Additionally, ATSDR’s reliance on these rodent studies is inappropriate because researchers
gave rodents large doses of PFAS that resulted in PFAS blood levels considerably higher than the
general population’s exposure today. ATSDR acknowledges the questionable relevance of these
animal studies to humans and that effects are seen only at large exposure levels in animals that
respond differently to PFAS exposures due to physiological differences. As ATSDR states: “[t]hese
factors [differences in doses and modes of actions between animals and humans]…make it
somewhat difficult at this time to determine the true relevance of some effects reported in animal
studies to human health.”13

ATSDR nevertheless mechanically extrapolates these exposures to so-called human-
equivalent doses to derive MRLs, and then applies the unsupported presumption that humans are
more sensitive to these effects than rodents. This cascade of errors renders ATSDR’s levels
scientifically unjustified and wholly unreliable. ATSDR should either rely on studies with more
direct relevance to humans, such as human or non-human primate studies, or take into account the
fact that rodents are much more sensitive to PFAS effects than humans are. At a minimum,
ATSDR should remove their uncertainty factor of three for animal to human extrapolation.

Second, ATSDR chose a study for its PFOA MRL derivation that is fatally flawed and that
researchers cannot use to derive a scientifically defensible MRL. This study only evaluated effects
in animals at a single dosing level, making it impossible to confirm that there was a positive-dose
response attributable to PFOA exposures. It is also impossible to determine the “point of
departure” (POD) from a “no observed adverse effect level” (NOAEL) or a “lowest observed
adverse effect level” (LOAEL).

Without that information, ATSDR cannot reliably derive MRLs from the study. In addition,
the study involved too few animals to generate reliable results and failed to follow standard
protocols. ATSDR should not use this study in its derivation.

Third, in extrapolating exposure levels from rodents to humans, ATSDR purported to
account for differences in the rate of PFAS clearance from blood between rodents and humans.
However, ATSDR utilizes PFAS human blood half-lives from groups exposed as part of their
occupations (e.g., a 5.4-year half-life for PFOS) that are excessive. This results in lower human
equivalent doses and lower MRLs. ATSDR should use the more realistic and relevant half-lives of
the general community.

Fourth, ATSDR improperly employs excessive and unnecessary uncertainty factors that
artificially lower the PFAS MRLs. For example, ATSDR should not use the uncertainty factor of
three for interspecies extrapolation (animal to human) for any of the MRLs, given that rodents are
more sensitive to the effects at issue than humans are.

In addition, ATSDR should not utilize an uncertainty factor of 10 in its PFOS or PFHxS
MRL derivations to account for potential immunological effects associated with PFAS. The 10-fold
factor is arbitrary and has not been justified. Notably, after reviewing the body of toxicology and
13 Id. at 10.

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epidemiologic studies examining the potential immune effects of PFOS, EPA did not include an
uncertainty factor of 10 for potential immunological effects in its derivation of the PFOS drinking
water guidance level.14

ATSDR should have reached a similar conclusion, because it otherwise acknowledges that
the human evidence for immune effects is insufficient to support causation.15 In addition, the
uncertainty factor of 10 that ATSDR used for PFOA for a LOAEL-to-NOAEL extrapolation is not
valid because the study design precluded establishing any LOEAL or NOAEL values. There is also
no reliable evidence that PFAS exposure increases the risk of infectious disease in humans.16
ATSDR should remove the potential immunological effects’ uncertainty factor of 10.

ATSDR’s PFAS MRLs are lower than virtually all of the 190-plus other chemicals for which
ATSDR has developed MRLs. As such, one can conclude that ATSDR’s PFAS MRLs are
excessively low. Notably, the PFOA and PFOS MRLs are lower than contaminants such as arsenic,
chromium, PCBs and parathion. Only the MRL for 2,3,7,8-TCDD (dioxin) is lower, and ATSDR
has described dioxin as one of the most highly toxic chemicals. Yet, ATSDR acknowledges that
there is insufficient evidence to conclude that PFAS causes any adverse effects in humans.

Finally, the PFAS blood levels experienced in the general population today are exponentially
lower than the blood levels in animal models experiencing adverse effects. It is imperative that
ATSDR base its regulatory guidance on credible, realistic, and scientifically based risk assessment.
ATSDR’s draft PFAS MRLs do not meet this standard. ATSDR should either withdraw them or
revise them to account for the issues identified above.

14 See, e.g., U.S. Environmental Protection Agency, EPA Response to External Peer Review Comments on EPA Draft
Documents: Health Effects Support Document for Perfluorooctanoic Acid (PFOA) and Health Effects Support
Document for Perfluorooctane Sulfonate (PFOS), (May 2016) available at
https://www.epa.gov/sites/production/files/2016-
05/documents/response_to_pfoa_pfos_peer_review_comments_508.pdf.
15 Draft Profile at 636.
16 Id. at 276, 282.

Agency for Toxic Substances and Disease Registry
August 20, 2018
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IV. Conclusion

The Chamber appreciates ATSDR’s consideration of these comments and urges the Agency
to withdraw or revise the Draft Profile, as the identified errors warrant a revision of the Draft
Profile. If you have questions regarding these comments, please contact me at (202) 463-5558 or at
kharbert@uschamber.com.

Sincerely,

Karen A. Harbert