Letters
Agency for arsenic in drinking water. The proposed action limit is based on quantitative risk assessment using data on lung and bladder cancer cases from southwestern Taiwan. The increasing evidence for arsenic health effects at low-to-moderate arsenic levels, including both cancer and noncancer end points,2-5 should be considered to evaluate the adequacy of 10 μg/L as the action level for apple juice. For rice, the FDA’s risk assessment is ongoing; an action level has yet to be proposed. As we discussed, in addition to establishing standards for juice, rice, and other foods, adequate monitoring systems are needed for arsenic species in food. Finally, on September 30, 2013, the FDA withdrew the approvals of roxarsone, arsanilic acid, and carbarsone, which are arsenic-based animal drugs.6 Thus, people who eat poultry may be less likely to be exposed to dietary arsenic. Nitarsone, however, is still approved. Ana Navas-Acien, MD, PhD Keeve Nachman, PhD, MHS Author Affiliations: Department of Environmental Health Sciences, Johns Hopkins Bloomberg School of Public Health, Baltimore, Maryland (Navas-Acien, Nachman); Department of Epidemiology, Welch Center for Prevention, Epidemiology, and Clinical Research, Johns Hopkins Bloomberg School of Public Health, Baltimore, Maryland (Navas-Acien); Department of Health Policy and Management, Johns Hopkins Center for Livable Future, Johns Hopkins Bloomberg School of Public Health, Baltimore, Maryland (Nachman). Corresponding Author: Ana Navas-Acien, MD, PhD, Department of Environmental Health Sciences, Johns Hopkins Bloomberg School of Public Health, 615 N Wolfe St, Office W7513D, Baltimore, MD 21205 ([email protected]). Conflict of Interest Disclosures: None reported. 1. US Food and Drug Administration. Supporting document for action level for arsenic in apple juice. http://www.fda.gov/Food/GuidanceRegulation /GuidanceDocumentsRegulatoryInformation/ChemicalContaminantsMetals -NaturalToxinsPesticides/ucm360023.htm. Accessed November 25, 2013. 2. Sohel N, Persson LA, Rahman M, et al. Arsenic in drinking water and adult mortality: a population-based cohort study in rural Bangladesh. Epidemiology. 2009;20(6):824-830. 3. Chen Y, Graziano JH, Parvez F, et al. Arsenic exposure from drinking water and mortality from cardiovascular disease in Bangladesh: prospective cohort study. BMJ. 2011;342:d2431. 4. García-Esquinas E, Pollán M, Umans JG, et al. Arsenic exposure and cancer mortality in a US-based prospective cohort: the Strong Heart Study. Cancer Epidemiol Biomarkers Prev. 2013;22(11):1944-1953. 5. Moon KA, Guallar E, Umans JG, et al. Association between low to moderate arsenic exposure and incident cardiovascular disease: a prospective cohort study [published online September 24, 2013]. Ann Intern Med. doi:10.7326/0003-4819-159-10-201311190-00719. 6. US Food and Drug Administration. FDA response to citizen petition on arsenic-based animal drugs. http://www.fda.gov/AnimalVeterinary/SafetyHealth /ProductSafetyInformation/ucm370568.htm. Accessed November 25, 2013.
Conflicts of Interest in Approvals of Food Additives To the Editor In concluding that financial conflicts of interest are ubiquitous in the conduct of “generally recognized as safe” (GRAS) determinations, Neltner et al1 fundamentally misunderstand the legal framework that governs the use of substances in food. The authors draw on principles regarding conflicts of interest that were articulated by the Institute of Medicine in the context of medical education, research, and practice. Nowhere do the authors explain why it is appropri-
ate to apply those principles in the context of a GRAS determination by a food manufacturer. It is not appropriate. In conducting a GRAS determination, a food manufacturer is not recommending a course of therapy to a patient or rendering an opinion on whether the Food and Drug Administration (FDA) should approve a drug. Rather, the manufacturer is exercising a responsibility explicitly conferred by the Federal Food, Drug, and Cosmetic Act. That law authorizes a manufacturer to determine whether the proposed use of a substance in food is GRAS (ie, whether the proposed use of the substance is safe and whether there exists general recognition among qualified experts of such safety). There is no question on whose behalf the manufacturer is acting. If the manufacturer errs in its GRAS determination, the manufacturer is subject to substantial civil and criminal liability. In some instances, it may be desirable for a manufacturer to convene a panel of experts to assess whether there exists general recognition of safety. Even in those instances, the ultimate responsibility for a GRAS determination rests with the manufacturer. A manufacturer therefore has strong incentives to seek out the most highly qualified food toxicologists (not food technologists) and other appropriately qualified experts to help the manufacturer determine whether there exists general recognition of safety among such experts. In the end, what the authors appear to object to is the fact that Congress chose to establish the GRAS statutory provision that charges manufacturers with the responsibility of determining when it applies. In the more than 50 years since the law was enacted, that choice has proven wise. Manufacturers have adhered to the law and regulations in order to facilitate innovations that have contributed to the production of safe, nutritious, and affordable food, and the FDA has been left free to focus its limited resources on matters that merit the agency’s attention. Leon Bruner, DVM, PhD Author Affiliation: Science and Regulatory Affairs, The Grocery Manufacturers Association, Washington, DC. Corresponding Author: Leon Bruner, DVM, PhD, Senior Vice President for Scientific and Regulatory Affairs, Grocery Manufacturers Association, 1350 I St NW, Ste 300, Washington, DC 20005 ([email protected]). Conflict of Interest Disclosures: None reported. 1. Neltner TG, Alger HM, O’Reilly JT, Krimsky S, Bero LA, Maffini MV. Conflicts of interest in approvals of additives to food determined to be generally recognized as safe: out of balance. JAMA Intern Med. 2013;173(22):2032-2036.
To the Editor The article by Neltner et al1 raises concerns about the integrity of the “Generally Recognized as Safe” (GRAS) process. The United States has the most robust assessment of food ingredient safety in the world. The current GRAS process relies on scientific expert consensus, publicly available information, and clinical data. GRAS ingredients have been consumed for decades, and none has compromised public health. Under the current self-affirmation GRAS process, expert reviewers are selected for their academic credentials and experience as specified in the statutes,2 promulgated in 1997 and
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Agency for arsenic in drinking water. The proposed action limit is based on quantitative risk assessment using data on lung and bladder cancer cases from southwestern Taiwan. The increasing evidence for arsenic health effects at low-to-moderate arsenic levels, including both cancer and noncancer end points,2-5 should be considered to evaluate the adequacy of 10 μg/L as the action level for apple juice. For rice, the FDA’s risk assessment is ongoing; an action level has yet to be proposed. As we discussed, in addition to establishing standards for juice, rice, and other foods, adequate monitoring systems are needed for arsenic species in food. Finally, on September 30, 2013, the FDA withdrew the approvals of roxarsone, arsanilic acid, and carbarsone, which are arsenic-based animal drugs.6 Thus, people who eat poultry may be less likely to be exposed to dietary arsenic. Nitarsone, however, is still approved. Ana Navas-Acien, MD, PhD Keeve Nachman, PhD, MHS Author Affiliations: Department of Environmental Health Sciences, Johns Hopkins Bloomberg School of Public Health, Baltimore, Maryland (Navas-Acien, Nachman); Department of Epidemiology, Welch Center for Prevention, Epidemiology, and Clinical Research, Johns Hopkins Bloomberg School of Public Health, Baltimore, Maryland (Navas-Acien); Department of Health Policy and Management, Johns Hopkins Center for Livable Future, Johns Hopkins Bloomberg School of Public Health, Baltimore, Maryland (Nachman). Corresponding Author: Ana Navas-Acien, MD, PhD, Department of Environmental Health Sciences, Johns Hopkins Bloomberg School of Public Health, 615 N Wolfe St, Office W7513D, Baltimore, MD 21205 ([email protected]). Conflict of Interest Disclosures: None reported. 1. US Food and Drug Administration. Supporting document for action level for arsenic in apple juice. http://www.fda.gov/Food/GuidanceRegulation /GuidanceDocumentsRegulatoryInformation/ChemicalContaminantsMetals -NaturalToxinsPesticides/ucm360023.htm. Accessed November 25, 2013. 2. Sohel N, Persson LA, Rahman M, et al. Arsenic in drinking water and adult mortality: a population-based cohort study in rural Bangladesh. Epidemiology. 2009;20(6):824-830. 3. Chen Y, Graziano JH, Parvez F, et al. Arsenic exposure from drinking water and mortality from cardiovascular disease in Bangladesh: prospective cohort study. BMJ. 2011;342:d2431. 4. García-Esquinas E, Pollán M, Umans JG, et al. Arsenic exposure and cancer mortality in a US-based prospective cohort: the Strong Heart Study. Cancer Epidemiol Biomarkers Prev. 2013;22(11):1944-1953. 5. Moon KA, Guallar E, Umans JG, et al. Association between low to moderate arsenic exposure and incident cardiovascular disease: a prospective cohort study [published online September 24, 2013]. Ann Intern Med. doi:10.7326/0003-4819-159-10-201311190-00719. 6. US Food and Drug Administration. FDA response to citizen petition on arsenic-based animal drugs. http://www.fda.gov/AnimalVeterinary/SafetyHealth /ProductSafetyInformation/ucm370568.htm. Accessed November 25, 2013.
Conflicts of Interest in Approvals of Food Additives To the Editor In concluding that financial conflicts of interest are ubiquitous in the conduct of “generally recognized as safe” (GRAS) determinations, Neltner et al1 fundamentally misunderstand the legal framework that governs the use of substances in food. The authors draw on principles regarding conflicts of interest that were articulated by the Institute of Medicine in the context of medical education, research, and practice. Nowhere do the authors explain why it is appropri-
ate to apply those principles in the context of a GRAS determination by a food manufacturer. It is not appropriate. In conducting a GRAS determination, a food manufacturer is not recommending a course of therapy to a patient or rendering an opinion on whether the Food and Drug Administration (FDA) should approve a drug. Rather, the manufacturer is exercising a responsibility explicitly conferred by the Federal Food, Drug, and Cosmetic Act. That law authorizes a manufacturer to determine whether the proposed use of a substance in food is GRAS (ie, whether the proposed use of the substance is safe and whether there exists general recognition among qualified experts of such safety). There is no question on whose behalf the manufacturer is acting. If the manufacturer errs in its GRAS determination, the manufacturer is subject to substantial civil and criminal liability. In some instances, it may be desirable for a manufacturer to convene a panel of experts to assess whether there exists general recognition of safety. Even in those instances, the ultimate responsibility for a GRAS determination rests with the manufacturer. A manufacturer therefore has strong incentives to seek out the most highly qualified food toxicologists (not food technologists) and other appropriately qualified experts to help the manufacturer determine whether there exists general recognition of safety among such experts. In the end, what the authors appear to object to is the fact that Congress chose to establish the GRAS statutory provision that charges manufacturers with the responsibility of determining when it applies. In the more than 50 years since the law was enacted, that choice has proven wise. Manufacturers have adhered to the law and regulations in order to facilitate innovations that have contributed to the production of safe, nutritious, and affordable food, and the FDA has been left free to focus its limited resources on matters that merit the agency’s attention. Leon Bruner, DVM, PhD Author Affiliation: Science and Regulatory Affairs, The Grocery Manufacturers Association, Washington, DC. Corresponding Author: Leon Bruner, DVM, PhD, Senior Vice President for Scientific and Regulatory Affairs, Grocery Manufacturers Association, 1350 I St NW, Ste 300, Washington, DC 20005 ([email protected]). Conflict of Interest Disclosures: None reported. 1. Neltner TG, Alger HM, O’Reilly JT, Krimsky S, Bero LA, Maffini MV. Conflicts of interest in approvals of additives to food determined to be generally recognized as safe: out of balance. JAMA Intern Med. 2013;173(22):2032-2036.
To the Editor The article by Neltner et al1 raises concerns about the integrity of the “Generally Recognized as Safe” (GRAS) process. The United States has the most robust assessment of food ingredient safety in the world. The current GRAS process relies on scientific expert consensus, publicly available information, and clinical data. GRAS ingredients have been consumed for decades, and none has compromised public health. Under the current self-affirmation GRAS process, expert reviewers are selected for their academic credentials and experience as specified in the statutes,2 promulgated in 1997 and
jamainternalmedicine.com
JAMA Internal Medicine February 2014 Volume 174, Number 2
Copyright 2014 American Medical Association. All rights reserved.
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