Dr. Dennis Keefe Director of the Office of Food Additive Safety
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NATURAL RESOURCES DEFENSE COUNCIL BREAST CANCER FUND CENTER FOR ENVIRONMENTAL HEALTH CENTER FOR FOOD SAFETY CENTER FOR SCIENCE IN THE PUBLIC INTEREST CHILDREN’S ENVIRONMENTAL HEALTH NETWORK CLEAN WATER ACTION ENVIRONMENTAL WORKING GROUP IMPROVING KIDS’ ENVIRONMENT October 17, 2014 (REVISED FROM VERSION FILED October 16, 2014) Dr. Dennis Keefe Director of the Office of Food Additive Safety (HFS-200) Center for Food Safety and Applied Nutrition 5100 Paint Branch Parkway College Park, MD 20740 Re: Petition seeking amended food additive regulation to remove FDA’s approval at 21 C.F.R. § 176.170 of the use of long-chain perfluorocarboxylate oil and grease repellents in paper and paperboard - Pre-Notification Consultation 1417 (PNC 1417) Dear Dr. Keefe: In 2010, the U.S. Food and Drug Administration’s (FDA) food additives toxicologists concluded that, in animal studies, long-chain perfluorinated compounds adversely affect fetal and newborn development and that one group of these compounds, long-chain perfluorocarboxylates1, adversely affect the male, and, possibly the female, reproductive systems.2 A ‘long-chain’ means the compound has eight or more carbons (“≥ C8”) connected together and the carbons are saturated with fluorine atoms. As the chain lengthens, FDA’s toxicologists noted that the chemical’s biopersistence, and hence potency, in the human body increases.3 These findings on long-chain perfluorocarboxylates expand on the toxicologist’s 2007 conclusion that carcinogenicity was a concern for chemicals that were structurally similar to the perfluorooctanoic acid (PFOA).4 The agency’s food additive toxicologists stated that “[d]ue to the considerable uncertainties remaining regarding the toxic effects of perfluorinated compounds as a class in humans, significant questions remain regarding the safe levels of dietary exposure to ≥ C8 perfluorinated 1 Including chemicals that may be converted to perfluorocarboxylates. 2 FDA Memo from Toxicology Group I to Regulatory Group 2 on September 30, 2010 at page 34-35. 3 Ibid., p. 34-35. 4 Ibid., p. 1. compound such that additional testing is recommended to ensure safety.”5 In other words, without additional testing, there was no longer a reasonable certainty of no harm from the intended uses of the long-chain perfluorinated compounds. Based on this conclusion, FDA took the unprecedented step of asking three companies with effective Food Contact Substance notifications (FCN) for perfluorocarboxylates to cease their sale and distribution in the United States.6 In 2011, all three voluntarily agreed.7 Despite this important step, three classes of long-chain chemicals that are likely to be converted to perfluorocarboxylates8 continue to be allowed to be used in paper and paperboard under FDA’s indirect food additive regulations at 21 C.F.R. § 176.170(a)(5). Table 1 and Appendix 2 provide details for each class. Table 1: Three classes of long-chain perfluorocarboxylates that NRDC is requesting FDA to remove from 21 C.F.R. § 176.170 Class Description of indirect additivea Company Year Max. Requesting Approved Estimated Approval Exposureb 1 Diethanolamine salts of mono- and bis DuPont 1967 0.013 mg (1H,1H,2H,2H perfluoroalkyl) phosphates / person / where the alkyl group is even-numbered in the day range C8-C18 and the salts have a fluorine content of 52.4% to 54.4% as determined on a solids basis 2 Pentanoic acid, 4,4-bis [(gamma-omega- Ciba-Geigyc 1983 0.05 mg / perfluoro-C8-20-alkyl)thio] derivatives, (now BASF) person / compounds with diethanolamine (CAS Reg. day No. 71608-61-2) 3 Perfluoroalkyl substituted phosphate ester Ciba-Geigyc 1996 & 0.13 mg / acids, ammonium salts formed by the reaction (now BASF) 1997 person / of 2,2-bis[ ([gamma], [omega]-perfluoro C4- day 20 alkylthio) methyl]-1,3-propanediol, polyphosphoric acid and ammonium hydroxide a See Appendix 2 for details on each class. b See Appendix 3. c Ciba-Geigy transferred this business to Ciba Specialty Chemicals in 1996. BASF purchased it in 2008. Because the agency did not follow-up its initiative on the above mentioned FCNs by taking the critical next step of revoking these approvals made decades earlier, any company, even those not 5 Ibid., p. 36. 6 See Appendix 6 for a description of the seven FCNs. 7 Ibid. 8 For convenience, we refer to chemicals that are likely to be converted to perfluorocarboxylates as part of the class of perfluorocarboxylates. 2 Food additive petition for perfluorocarboxylates requesting FDA’s approval, can continue using the chemicals listed on Table 1in pizza boxes, sandwich wrappers, and other food packaging without FDA’s or the public’s knowledge. While the shutdown of domestic production of these chemicals has minimized their use and most food product manufacturers may no longer rely on them, new overseas production in China and India could easily fill the void without FDA’s knowledge. After reviewing the literature9 published since FDA reached its conclusions that there was insufficient scientific data supporting the safety of long-chain perfluorocarboxylates, the Natural Resources Defense Council (NRDC) found that the evidence of adverse health effects caused by these chemicals has only strengthened since 2010. We identified 10 additional animal studies, an epidemiological study and three systematic reviews that were published between 2009 and 2014. All supported FDA’s toxicology conclusions that significant gaps remain in our knowledge of the safety of long-chain perfluorocarboxylates regarding pre-natal and post-natal developmental toxicity endpoints, reproductive health and function in males, and reproductive health in females. Particularly compelling were 1) A systematic, objective and transparent review of the scientific literature on PFOA concluding that there is sufficient human evidence that developmental exposure to PFOA reduces fetal growth;10 and 2) The U.S. Environmental Protection Agency’s (EPA) draft comprehensive analysis11 of the health effects of PFOA released in February 2014. EPA’s draft report established a reference dose12 of 0.00002 mg PFOA per kg of body weight per day (mg/kg-bw/day). For comparison, a 60 kg adult consuming 3 kg of food a day and the maximum exposure estimates listed in Table 1 would have an Estimated Daily Intake (EDI) for the three classes of additives would range from 0.00022 to 0.0022 mg/kg-bw/day – 10 to 100 times greater than EPA’s draft Reference Dose for PFOA. We understand that PFOA may be only a small component in the three classes of perfluorocarboxylates in Table 1 and the chemicals may not be readily metabolized to PFOA in the body. However, they are structurally similar, leading us to conclude that the FDA’s concerns about the health effects of PFOA in 2010 also apply to the three classes of chemicals mentioned above. Therefore, perfluorocarboxylates are: Likely to adversely affect fetal and neonatal development; Likely to adversely affect the male, and, possibly the female, reproductive systems; and Likely to cause cancer. 9 See Appendix 4 and 5 for review. 10 Johnson PI et al. The Navigation Guide—Evidence-Based Medicine Meets Environmental Health: Systematic Review of Human Evidence for PFOA Effects on Fetal Growth. 2014. Environmental Health Perspectives 122:1028-1039. http://dx.doi.org/10.1289/ehp.1307893 11 EPA, External Peer Review of EPA’s Draft Health Effects Documents for Perfluorooctanoic Acid (PFOA) and Perfluorooctane Sulfonate (PFOS), http://peerreview.versar.com/epa/pfoa/. (Accessed March 17, 2014). The two documents are “Health Effects Document for Perfluorooctanoic Acid (PFOA)” (EPA Doc. No. 822R14001) and “Health Effects Document for Perfluorooctane Sulfonate (PFOS)” (EPA Doc No. 822R14002) (2014). 12 For dietary exposures, a reference dose is developed in a manner consistent with FDA’s Acceptable Daily Intake or ADI. 3 Food additive petition for perfluorocarboxylates These effects are even more significant because these chemicals, like PFOA, are likely to persist in the human body in ways not fully understood decades ago when FDA made its original safety decisions to approve the use of these chemicals. Given the dearth of toxicology studies on these three classes of chemicals, without evidence showing that these chemicals impact the human body differently than PFOA, there is no longer “a reasonable certainty in the minds of competent scientists that the substance is not harmful under the intended conditions of use” as required by the FFDCA and 21 C.F.R. Parts 170 and 171. In other words, the uses allowed by the rule are not safe per 21 C.F.R. § 170.3(i). Therefore, the Natural Resources Defense Council (NRDC) submits this food additive petition, pursuant to section 409(b)(l) of the Federal Food, Drug, and Cosmetic Act (FFDCA), 21 C.F.R. § 171.130, requesting that FDA revoke the approved uses of the perfluorocarboxylates in 21 C.F.R. § 176.170 as described in Table 1.13 By making this change, any company seeking to use long-chain perfluorocarboxylates would need to notify FDA by submitting a FCN or food additive petition before commencing the use. Acceptance of this petition would complement actions taken by the U.S. Environmental Protection Agency (EPA) pursuant to the Toxic Substance Control Act (TSCA).14 Using Section 5 of TSCA, EPA has issued Significant New Use Restrictions (SNURs) under 40 C.F.R. §§ 721.982 and 721.10536 from 2000 to 2013 that today require the agency be notified of new uses of various long-chain perfluorinated compounds.15 If a chemical’s use is subject to a SNUR, the importer or manufacturer must notify the EPA 90 days before commencing import or manufacture. In addition, in 2006 EPA prohibited the use of Class 2 perfluorcarboxylate in Table 1 as an inert ingredient in pesticides applied to food because the potential risks meant the agency was unable to determine that the use met the safety requirements of the Section 408(c)(2) of the Federal Food Drug and Cosmetic Act.16 The reasonable certainty of no harm safety standard used by EPA to make it decision is essentially the same as the one FDA must use for food additives.